Pharmaceutical preparation comprising an active dispersed on a matrix

专利摘要:
The present invention relates to the field of pharmaceutical techniques and to novel and beneficial formulations for the active ingredients. Such novel formulations are suitable for producing many pharmaceutical dosage forms. In such new formulations, the active ingredient is present in a substantially uniform dispersion in an excipient matrix consisting of one or more excipients selected from the group of fatty alcohols, triglycerides, partial glycerides and fatty acid esters.
公开号:KR20030072557A
申请号:KR10-2003-7007647
申请日:2001-12-06
公开日:2003-09-15
发明作者:디트리히랑고；린더루돌프；나이하르트무트
申请人:알타나 파마 아게；
IPC主号:

专利说明:

Pharmaceutical preparations comprising the active ingredient dispersed on a matrix {PHARMACEUTICAL PREPARATION COMPRISING AN ACTIVE DISPERSED ON A MATRIX}
[2] In order to obtain certain properties of the dosage form, for example, masking of taste in the case of an active ingredient with an unpleasant taste, resistance to gastric juice in the case of an acid labile active ingredient or controlled release of the active ingredient, The component pellets will be provided with a suitable functional coating. If such coated pellets are further processed into a dosage form, for example by molding using tablets with excipients, by compression, there is a risk that the coating may be impaired, and therefore its functionality, at least in part.
[1] The present invention relates to pharmaceutical techniques and to novel and beneficial formulations for the active ingredient. Such novel formulations are suitable for the preparation of many pharmaceutical dosage forms.
[3] It is an object of the present invention to provide formulations for the active ingredients which can retain certain functionality and can be further treated with a plurality of pharmaceutical treatment formulations with little compromise to the desired functionality.
[4] Surprisingly, this object is achieved by a formulation wherein the active ingredient is substantially uniformly dispersed in an excipient matrix consisting of one or more excipients selected from the group of fatty alcohols, triglycerides, partial glycerides and fatty acid esters.
[5] The present invention therefore relates to a formulation wherein the active ingredient is substantially uniformly dispersed in an excipient matrix consisting of one or more excipients selected from the group of fatty alcohols, triglycerides, partial glycerides and fatty acid esters.
[6] It has also been found that this particularly advantageous formulation can be obtained by adding solid paraffin to the excipient matrix. Therefore, the present invention relates to a formulation wherein the active ingredient is dispersed substantially uniformly in an excipient matrix consisting of one or more solid paraffins with one or more excipients selected from the group of fatty alcohols, triglycerides, partial glycerides and fatty acid esters.
[7] The present invention relates to an excipient matrix in which the active ingredient comprises i) at least one fatty alcohol and at least one solid paraffin, ii) at least one triglyceride and at least one solid paraffin. iii) substantially uniformly dispersed in an excipient matrix consisting of a mixture comprising at least one partial glyceride and at least one solid paraffin or iv) in an excipient matrix consisting of a mixture comprising at least one fatty acid ester and at least one solid paraffin. It relates to a formulation.
[8] Further objects of the invention will be apparent from the claims.
[9] Formulations for the purposes of the present invention comprise a number of individual units (hereinafter referred to as active ingredient units) in which at least one active ingredient particle, preferably a plurality of active ingredient particles, is present in an excipient matrix consisting of the excipient of the invention. It is desirable to. Such active ingredients are preferably dispersed substantially uniformly in the excipient matrix, in particular homogeneously dispersed or dissolved. The formulation preferably comprises microspheres.
[10] The formulations of the present invention are characterized by high stability, release of the active ingredient which can be controlled by the composition and particle size of the matrix, good flow properties, good compressibility and uniform delivery of the active ingredient. In addition, in the case of acid labile active ingredients, acid resistance can be obtained by selecting the matrix excipients so that they can be formulated into an acid resistant coating (enteric coating) in oral formulation. In the case of an active ingredient having an unpleasant taste or for example a local anesthetic effect in the mouth after administration, the unpleasant taste of the active ingredient can be masked by the formulations of the invention and the anesthetic effect in the mouth can be avoided. It is important that the formulations of the present invention can be further treated with a number of pharmaceutical dosage forms without losing certain functionality (eg, masking taste, resistance to gastric juice, delay in release). Thus, for example, upon compression of the active ingredient units of the invention, no or little loss of function is observed even if deformation of the active ingredient units occurs. In contrast, conventional pellets, which typically have a functional coating (e.g., taste, resistance to gastric juice, retardation of release), cause some damage to the coating upon further treatment with the dosage form, such as compression on tablets. Loss of function is observed. It may also in some cases cause the active ingredient to be released in an unwanted manner.
[11] The particle size of each unit is advantageously 2 mm or less, preferably 50 to 800 µm, particularly preferably 50 to 700 µm, very particularly preferably 50 to 600 µm. The particle size of the microspheres is 50 to 500 µm, particularly preferably 50 to 400 µm. Particular preference is given to monomodal microspheres having a particle size of 50 to 400 μm, in particular 50 to 200 μm.
[12] The active ingredient of the present invention is in particular an active pharmaceutical ingredient. Active ingredients that can form part of the formulations of the invention are in particular the active pharmaceutical ingredients set forth below.
[13] Adrenaline
[14] Apraclonidine; Brimonidine; Dapiprazole; Deterenol; Dipiberine; Dopamine; Ephedrine; Esproquine; Etaphedrine; Hydroxy amphetamine; Levonordephrine; Metaramimin; Norepinephrine; Oxidopamine; Phenylpropanolamine; Prenalterol; Propylhexedrine; Pseudoephedrine.
[15] Adrenocorticosteroids
[16] Cyprosinoneide; Desoxycorticosterone acetate; Dexoxycorticosterone pivalate; Dexamethasone acetate; Fludrocortisone acetate; Flumoksonide; Hydrocortisone hemisuccinate; Methylprednisolone hemisuccinate; Naflocorte; Prosnonide; Thymobeson acetate; Tipredan.
[17] Alcohol abuse inhibitors
[18] Disulfiram, acamprosate, milnacipran, pomepisol, razabemide, nadide; Nitrepazole; Sunepitron.
[19] Aldosterone antagonists
[20] Canrenoate; Canrenon; Disylenone; Mexrenoate; Prorenoate; Spironolactone, epostane, mespyrenone; Oxprenoate, spirorenone, spiroxazone, prorenone, eplerenone.
[21] amino acid
[22] Alanine; Aspartic acid; Cysteine; Histidine; Isoleucine; Leucine; Lee Sin; Methionine; Phenylalanine; Proline; Serine; Threonine; Tryptophan; Tyrosine; Valine.
[23] Active ingredient for ammonium detoxification
[24] Arginine; Arginine glutamate; Arginine hydrochloride; Glutamic Acid,
[25] Assimilation agents
[26] Androstanolone, bolandidiol dipropionate; Bolosterone; Booldenone undecylenate; Bolenol; Ballnantalate; Ethyl estrenol; Methenolone acetate; Methenolone enanthate; Volazine; Mesteronol; Metadienone; Nandrolone; Oxandrolone; Prasterone; Stanozolone; Thiomesterone; Clostebol; Mivolerone; Nandrolone cyclotate; Norvoletone; Quinbolone; Stenbolone acetate; Tibolone; Geranol.
[27] tonic
[28] Modafinil; Amineftine; Endomid; Etamiban; Phenoxypropazine; Phenozolones; Hexapradol; Nialamide; Nisetamide.
[29] painkiller
[30] Acetaminophen; Alfentanil; Aminobenzoate; Aminobenzoate; Anxiety; Aniliridine; Aniliridine; Anilofam; Anirolact; Antipyrine; aspirin; Benoxapropene; Benzidamine; Bicipadin hydrochloride; Brifentanil; Bromadolin; Bromfenac; Buprenorphine; Butacetin; Butycirate; Butorpanol; Butorpanol; Butorpanol; Carbamazepine; Carbaspirin calcium; Carbifen; Carfentanil; Ciprepadol succinate; Siramadol; Siramadol; Clonicseryl; Clonicin; codeine; Codeine phosphate; Codeine sulfate; Conorphon; Cyclazosin; Dexosadrol; Dexfemedolac; Dezosin; Diflunisal; Dihydrocodeine; Dimefadan; Diffyrone; Doxicocomin; Driniden; Enadoline; Epirisol; Ergotamine tartrate; Ethoxazene; Etophenamate; Eugenol; Phenopropene; Phenopropene calcium; Fentanyl citrate; Flocfenin; Flufenical; Flunicin; Flunicin meglumine; Flupyritin; Fluprocuazone; Fluladoline; Flubiprofen; Hydromorphone; Ibufenac; Indopropene; Ketazosin; Ketorpanol; Ketorolac; Retimid; Levomethadyl acetate; Levomethadyl acetate hydrochloride; Levonanthradol; Levorfanol; Lofemizol; Lofentanyl oxalate; Sorbinadol; Romoxicam; Magnesium salicylate; Mefenamic acid; Menabitan; Meperidine; Meftazinol; Methadone; Metadyl acetate; Metopoline; Metotrimeprazine; Metkepamide acetate; Memban; Mirfentanil; Molinazone; Morphine sulfate; Pastoral care; Navitan; Nalbuphine; Nalmexone; Namoxilate; Nantradol; Naproxen; Naproxen; Naproxol; Nepofarm; Nexeridine; Norasimetadol; Octafentanyl; Octazamide; Albanyl; Oxetrone; Oxycodone; Oxycodone; Oxycodone terephthalate; Oxymorphone; Femedolac; Pentamorphone; Pentazosin; Pentazosin; Phenazopyridine; Peniramidol; Pisenadol; Pinadolin; Pirfenidone; Pyoxycham olamine; Pravadoline; Prodillidine; Propadol; Propiram; Propoxyphene; Propoxyphene lead silate; Proxazole; Proxorphan; Pyrrolifen; Remifentanil; Salcorex; Saletamide maleate; Salicylate; Salicylate meglumine; Salsalate; Salicylate; spiradoline; Serfentanil; Serfentanil; Tametacin; Talni flu mate; Thalosalate; Tazadolene; Tebupelone; Tetridamine; Thifurac; Tilidine; Thiopinac; Tonazosin; Tramadol; Trefentanil; Trolamine; Veradolin; Berillomine; Bolazosin; Zopanol; Xylazine; Zenazosin mesylate; Zomepilac; Sucapsaicin.
[31] Androgen
[32] Androstanolone; Fluoxymesterone; Mestanolone; Mesterolone; Methanedienone; Methyltestosterone; Nandrolone decanoate; Nandrolone phenpropionate; Nistherim; Oxandrolone; Oxymesterone; Oxymetholone; Fensterol; Prasterone; Sillandrone; Stanozolol; Testosterone; Testosterone cypionate; Testosterone enanthate; Testosterone ketoraurate; Testosterone phenylacetate; Testosterone propionate; Trestolone.
[33] Anesthetic additive
[34] Sodium oxybate.
[35] Anesthetic (Non-Suction)
[36] Alfaxalone; Amolanone; Ethoxadrol; Fentanyl; Ketamine; Reboxadrol; Methitural; Methohexital; Midazolam; Minoxolone; Propanide; Propoxate; Pramoxin; Propofol; Remifentanil; Serfentanil; Tiletamine; Zolamin.
[37] Anesthetic (Local)
[38] Ambucaine; Amocecaine; Amylocaine; Aftokine; Articaine; Benoxynate; Benzyl alcohol; Benzocaine; Bethoxycaine; Biphenamine; Bucrycaine; Bomecaine; Bupivacaine; Butamben; Butanilicaine; Carbiczocaine; Chloroprocaine clebucaine; Clodakine; cocaine; Dexivacaine; Diamocaine; Dibucaine; Diclonin; Elucine; Ethidocaine; Euprocin; Fexycaine; Formocine; Heptacaine; Hexylcaine; Hydroxyprocaine; Hydroxytetracaine; Isobutambene; Ketocaine; Rheinokine; Lidocaine; Mepivacaine; Meprylcaine; Octocaine; Orthocaine; Oxetacaine; Oxybuprocaine; Parabutoxycaine; Phencaine; Plenocaine; Piperocaine; Pyridocaine; Polydocanol; Pramokine; Prilocaine; Procaine; Propanocaine; Propofokine; Propoxycaine; Proxy metacaine; Pyrocaine; Quaatacaine; Quinisocaine; Lysocaine; Rhodokine; Ropivacaine; Salicylic alcohol; Suicain; Tetracaine; Trafencaine; Trimecaine.
[39] Appetite suppressant
[40] Ampfepramon; Amphetamine; Aminorex; Ampekchloral; Anisacryryl; Benzpetamine; Chlorpentermine; Clobenzox; Cloforex; Clominorex; Chlortermin; Dexampetamine; Dexfenfluramine; Difemethorex; Ethamphetamine; Etolorex; Fenbutrazate; Phencampamine; Fenfluramine; Phenixorex; Fenprophorex; Fludorex; Fluminorex; Formetorex; Purenorex; Imanic room; Indanorex; Rebampetamine; Levopacetoferan; Levofenfluramine; Levopropylhexane; Margin stones; Mefenorex; Methamfepramon; Morphorex; Norfsuedophedrine; Orlistat; Ortetamine; Oxypentorex; Pentorex; Pendimethazine; Penmetrazine; Phentermin; Picillorex; Satietin; Thetazindol; Sibutramine; Triplerolex; Trifluorex.
[41] helminthic
[42] Abamectin; Albendazole; Albendazole oxide; Amidantel; Amoscanate; Antafenite; Anthagonite; Antelmycin; Antholimine; Bephenium hydroxynaphthoate; Bidimagium iodide; Bisbendazole; Bithionolide; Vitoscanate; Bromosanide; Brotianide; Bunamidine; Butamisol; Butonate; Cambendazole; Carvantel; Cyclobendazole; Cliosanide; Chlosantel; Dexamisol; Diophenetide; Dichlorbos; Diethylcarbazine; Dimantin; Diphenan; Doramectin; Dribendazole; Eprinomectin; Fsifrantel; Etibendazole; Pevantel; Fenbendazole; Flubendazole; Flulantel; Phthalopins; Furodazole; Haloxone; Hexylesorcinol; Amcarbophos; Ivermectin; Caric acid; Mebendazole; Metriponate; Methiridine; Morantel; Moxidecin; Naphthalophos; Netobimine; Niclopolan; Niclosamide; Nitramisol; Nitrodans; Nitroscanates; Nitroxynyl; Oltipraz; Ontranyl, oxantel oxpendazole; Oxybendazole; Oxcyclozanide; Parbendazole; Pesantel; Piperamide; Piperazine adipate; Piperazine calcium edetate; Piperamide Frazikuantel; Prolonol; Pyrantel pamoate; Pyrantel tartrate; Pirvinium pamoate; Lapoxanide; Lesolantel; Salantel; Spirazine; Steel ring iodide; Suvendazole; Tetramisol; Tenium closylate; Thiofuraden; Thiavenazole; Ticarbodine; Thioxidazole; Triclabendazole; Triclophenol piperazine; Uredofoss; Vincorpos; Zilandel.
[43] Acne Remedies
[44] Adapalene; Adelmidol; Benzoyl peroxide; Beta carotene; Cytheronel; Delanthone; Cyproterone; Doretinel; Erythromycin salasedine; Etretinate; Fumaric acid; halofuginonene; Inocoteron acetate; Isotretinoin; Linolenic acid; Anolides; Masoprocol; Mitotan; Mortretinide; Namirotene; Rosterellon; Sumarothene; Tazarotene; Tematoten; Thioxolone; Tofterone; Tradecamide; Tretinoin; Triadimenol; Zealenone; Geranol; Jimmy Doben.
[45] Bronchodilator
[46] Acepiline; Azaspirium chloride; Bambuterol; Vamiphylline; Bitototerol; Broxaterol; Butafrost; Carbuterol; Sifamphyline; Colterol; Doxafrost; Doxophylline; Depilin; Enpropylin; Ephedrine; Eprozinol; Ethaneterol; Fenpyride; Flutropium bromide; Formoterol; Guatilin; Hexoprelinin; Hoku-81; Hokujil; Dimoxiterol; Ifpragratin; Ifpratropium bromide; Isotarin; Isoproterenol; Levosalbutamol; Mabuterol; Mekuitamium iodide; Metaproterenol; Mexafilin; Nartherolol; Nestiphylline; Nisbuterol; Picumeterol; Picuisol; Pirbuterol; Procaterol; Leproterol; RO-24-4736; Quazodidine; Quinterenol; Racepinephrine; Leproterol; Limiterol; Salbutamol; Salmeterol; Salmeterol ginafoate; Cebitlopium mesylate; Soterenol; Sulfonterol; Sulfoxyphene; TA-2005; Theophylline; Terbutalin; Theophylline ethylenediamine; Tiaramid; Tifetropium bromide; Tretoquinol; Tulobuterol; Cindotrin; Ginterol.
[47] Beta-blocker
[48] Acebunolol; Adaprolol; Afurolol; Alprenolol; Alprenoxim; Ancarolol; Arnolol; Arotinol; Atenolol; Befunolol; Benzodioxin; Betaxolol; Bevantolol; Bisoprolol; Bormetholol; Bopindolol; Bornaprolol; Breponalol; Bucumolol; Bufetolol; Bufuralol; Bunitrolol; Bunolol; Bupranolol; Askmin; Butidrin; Brocrolol; Butopyrrole; Carazolol; Carteolol; Carvedilol; Celiprolol; Cetamolol; Cycloprolol; Cinnamolol; Chloranol; Cyanopindolol; Dalbraminol; Dexpropranolol; Diacetolol; Dichlorosoproterenol; Dilevalol; Draquinolol; Dropranolol; Decastolol; Epanolol; Erycolol; Esathenolol; Esmolol; Exaprolol; Palintolol; Plestolol; Fluxosolol; Hydroxycarteolol; Hydroxytertatolol; ICI-118551; Idropranolol; Indenolol; Indopanolol; Iprocrolol; Isamoltan; la-betalol; Randiolol; Levobetaxolol; Levobunol; Levocycloprolol; Levomoprolol; Medroxalol; Mefenoxalone; Mepindolol; Metal rolls; Metipranolol; Metoprolol; Mindodilone; Morphrolol; Nadolol; Nadoxolol; Nafetolol; Napitan; Nebivolol; Neraminol; Nifenalol; Nipradilol; Oberadilol; Oxanamid; Oxprenolol; Faclinolol; Paphenolol; Parmatolol; Pargolol; Parodidyl; Fenbutolol; Phenyrolol; PHQA-33; Pindolol; Pyrepolol; Practolol; Prenalterol; Primidolol; Pronolol; Pronetalol; Propacetamol; Propranolol; Lactopamine; Lidazolol; Ronactolol; Soquinolol; Sotalol; TA-2005; Thalinolol; Tazolol; Teofrolol; Tertatolol; Tertianolol; Thienoxolol; Tilisolol; Timolol; Thiprenolol; Tolamolol; Toliprolol; Tribendilol; Trigebolol; Zamotrol; Gibenolol; Y-12541; ZAM1-1305.
[49] Adrenergic Agonists
[50] Betanidine; Bretilium tosylate; Chromainidine; Debrisoquine; Etomoxane; Guavenic acid; Guanabenz; Guanacline; Guanadrel; Guanazodine; Guancidine; Guanclopin; guanetidine; Guanfacin; Guanisoquin; Guanochlor; Guanotin; Guanoxabenz; Guanoxane; Guanoxyphene; Olimidine; Piperonic acid; Piroxamidine; Solipertin; Spirghtine.
[51] Alpha 1 Antagonist
[52] Abanoquil; Adozelesin; Alfuzosin; Amosulalol; Benoxatian; Bunazosin; Cl-926; DL-017; Dapiprazole; Dihydroergotamine mesylate; Doxazosin; Eugenodylol; Fenpyride; GI-231818; GYKI-12743; GYKI16084; Indolamin; Metazosin; MK-912; Monatefil; Naphthopidyl; Neldazosin; Nesapidil; Nisergoline; Pelanserine; Peradoxime; Ferraquinine; Raatizol; Perbuphylline; Pendioxane; Phenoxybenzamine; Pentolamin; Podilfen; Prazosin; Quinazosin; RS-97078; Proroxane; Sertindol; SGB-1534; SL-89.0591; Tamsulosin; Teddysamyl; Terrazosin; Tivalosine; Thiodazosin; Tolazoline; Trimazolesin; Wopidocin; Urapidyl; Yohimbine; Zolertin.
[53] ACE inhibitor
[54] Alacepril; Benazepril; Benazeprillat; BMS-189921; BRL-36378; Captopril; Seronapril; CGS-13928C; Silazapril; Sialzaprilat; Dehydrocaptopril; Delapril; Enalapril; Enalapril; EU-4867; EXP-7711; Facidotril; Fosinopril; Phosphinoprilat; Isdrapril; Imidapril; Imidaprilat; Indrolapril; Ribenzapril; Lisinopril; Mexanpril; Moexipril; Moexiprilat; Moveltyril; Omapatrilat; Orbutopril; Pentopril; Perindopril; Ferindoprilat; Fibopril; Quinapril; Quinaprilat; Ramipril; Lentiapril; Sampatrilat; SCH-54470; Spirapril; Spirapril; Temocapryl; Temocaprylat; Teprotide; Trandolapril; Trandolaprillat; Utivapril; Utivaprilat; Z-13752A; Zabicipril; Jofenofril; Zofenopriat.
[55] Lenin antagonist
[56] CGP-38560; Ciprochirene; CP-108671; Enalkyrene; ES-6864; FK-906; Remicylene; Terlachiren; Jankyren.
[57] Anti-allergic agents such as PDE inhibitors
[58] Arophylline; Atizora, AWD-12-281 (N- (3,5-dichloro-4-pyridinyl) -2- [1- (4-fluorobenzyl) -5-hydroxy-1H-indol-3-yl] 2-oxoacetamide); BAY-19-8004 (ethanesulfonic acid 2- (2,4-dichlorophenylcarbonyl) -3-ureido-benzofuran-6-ylester); Benafenthrin; CC-1088; CDC-801 (β- [3- (cyclopentyloxy) -4-methoxyphenyl] -1,3-dihydro-1,3-dioxo-2H-isoindole-2-propanamide); CDC-998; CI-1018; Silomilast (cis- [4-cyano-4- (3-cyclopentyloxy-4-methoxyphenyl) cyclohexane-1-carboxylic acid); Cilostazol; Sifamphyline (8-amino-1, 3-bis (cyclopropylmethyl) xanthine); D-4396; D-4418 [N- (2,5-Dichloro-3-pyridinyl) -8-methoxy-5-quinoline-carboxamide]; Darbupelon; Denbuphylline; ER-21355; Filaminast; Ibudilast; IC-485; Indolidan; Lapraphylline; Lyxazinone; MESOPRAM [(-)-(R) -5- (4-methoxy-3-propoxyphenyl) -5-methyloxazolidin-2-one]; Nitraquazone; NM-702; Allprinon; ORG-20241 (4- (3,4-dimethoxyphenyl) -N2-hydroxythiazole-2-carboxamidine); Picclamilast; Fumapentrin ((-)-cis-9-ethoxy-8-methoxy-2-methyl-1,2,3,4,4a, 10b-hexahydro-6- (4-diisopropylaminocarbonyl Phenyl) benzo [c] [1,6] -naphthyridine); Quaazinone; RO-15-2041; Rafflemylast (3- (cyclopropylmethoxy) -N- (3,5-dichloro-4-pyridyl) -4- (difluoromethoxy) benzamide); Rolipram; SCH-351591; SH-636; Tibenelast (5,6-diethoxybenzo [b] thiophene-2-carboxylic acid); Tolapentrin; Trequinine; V-11294A (3-[[3- (cyclopentyloxy) -4-methoxyphenyl] methyl] -N-ethyl-8- (1-methylethyl) -3H-purin-6-amine); YM-58997 (4- (3-bromophenyl) -1-ethyl-7-methyl-1,8-naphthyridin-2 (1H) -one); YM-976 (4- (3-chlorophenyl) -1,7-diethylpyrido [2,3-d] pyrimidin-2 (1H) -one); Cutdarin.
[59] Other antiallergic agents for the treatment of asthma
[60] Ablue caste; Atreleutone; Bunaprolast; Cinnalukast; Chlornitrile; Chromoline; FPL-55712; Iralukast; Issamoksol; Ketotifen; L-648051; Rev chromacalim; Rodoxamide ethyl; Rhodoxamide tromethamine; Montelukast; Oxarbazole; Pyrifrost; Pyrrolate; Pobilicast; Franlukast; Ritlukast; Sulcastes; Tiaramid; Tibenerast; Tomelucaste; Berlucast; Verophylline; Zafirlukast; Zileuton.
[61] Other anti-allergic agents (eg, leukotriene antagonists)
[62] Acitazanolast; Acrivastin; Alinastin; Altoqualine; Amlexanox; Andolist; Astimazole; Atacumast; Azatadine; Azelastine; Bamipin; Barmastine; Batebulast; BAY-X-1005; BAY-X-7195; Bepiastin; Bepotastine; BIIL-284; Villastin; Vinizolast; Buclizine; Bunaprolast; Carvastin; Carebastin; Cetirizine; CI-959; Cyproxyxane; Clemastine; CMI-977; Chromoglic acid; Chromoline natrium; Dametralast; Desloratadine; Dimenhydrinate; Diphenhydramine; Docualast; Dorastin; E-4704; Epletirizine; Emedastine; Enofelast; Enoxamas; Evastin; Eclazolast; Efinastin; Fexofenadine; Flezelastine; HSR-609; KCA-757; Levocavastin; Levocetirizine; Lineastine; Loratadine; LY-293111; Mafinastine; Mequitium iodide; Mequitazine; Minocromyl, mizolastine; MK-886; Moxastin; Moxirubant; Nedocromil; Nedocromil calcium; Nedocromil sodium; Nibimedone; Noverastin; Norastimazole; Octastin; ONO-4057; Ontazolast; Oxatomide; Femirolast; Pentageted; Perastin; Picclophystin; Picumast; Pircuinosol; Poisonoac extract; Probichromyl; Proxycromil; Quaazolast; Cupfenadine; Quinotolast; Laxoplast; Repirinast; REV-5901-A; Locustine; Lupatadine; SKF-S-106203; Sequifenadine; Ceastine; Sudexanox; Taridazine; Thalastine; Tazanolast; Tajiphiline; Temelastin; Terpenadine; Tetrazolast; Taxacromil; Thiazinium chloride; Thiacrylast; Photonast meglumine; Thixanox; Tranilast; WY-50295; ZD-3523; Jeffastine.
[63] Amoeba Remedies
[64] 1B-bisamidine; Verithromycin; Non-alamicol; Carbarson; Chloroquine; Chloroquine; Clamoxiquin; Clioquinol; Dehydroemtin; Difetarson; Diloxanide; Emethine; Etopamide; Iodoquinol; Racnumon; Riroldine; Paromomycin sulfate; Pina feed; Quinamide; Satranidazole; Stevaladyl; Styriazole; Cimetin; Teclozan; Tetracycline; Tilbroquinol.
[65] Antiandrogen
[66] Abiraterone; Benorterone; Cytheronel; Cyproterone; Delanthone; Delmadinone; Drospirenone; Epithiostanol; Inocoteron; L-654066; Minamestan; Norgestimate; Ostherone; Oxendolone; Progesterone; Rosterone; Toprelon; Zanoteron.
[67] Anti-anemia
[68] Ancess team; Diciferon; Epoetin alfa; Epoetin beta; Epoetin epsilon; Epoetin gamma; Epoetin omega; Iron sulfate, FK-352; Folic acid; Gloptoferon; Glutathione monoisopropyl ester; Leucovorin calcium; Tucaresol; TYB-5220; Bellaresol.
[69] Antiangina
[70] Alinidine; Amiodarone; Amlodipine besylate; Amlodipine maleate; Azachlorzin; Barnidipine; Bertosamil; Betasolol; Bertosamil; Bevantolol; Bimacalim; Butoprozin; Carvedilol; CD-832; CERM-11956; Cinepazette maleate; Crobenetine; Cyclobirubuksin-D; Desochriptin; Diproteberine; Dopropidyl; Elgodipine; EMD 57283; Enporide; Etaxigin; Pantoparon; FK-409; Plestolol; Flosatidyl; Florcequinan; FR-46171; GP-1468; GP-1-531; Hyperin; Ipramidyl; Isosorbide dinitrate; Ivabradine; KC-764; KRN-2391; KW-3635; Ligustigin; Lincidomin; Metoprolol succinate; Mibepradil; Milldronate; Mibazerol; Molecidomin; Monatefil maleate; Napagrerel; NK-341; OP-2000; Pyrcidomin; Fiazide; Pranidipine; Primidolol; Ranolazine; SL-87.0495; ST-1324; Teddysamyl; Tocifen; Batanidipine; Verapamil; Y-27152; Zathebradin.
[71] Anti-anxiety
[72] Adatanserine; Alpidem; Vinospyrone mesylate; Brettazenyl; Glemanserine; Incidence theory; Myristicone maleate; Ossinaflon; Ondansetron; Panadiflon; Pancopride; Phagenaclones; Serazapine; Ballisticon citrate; Zalospiron.
[73] Antiarthritis
[74] Al-200; Auranopine; Aurothioglucose; Cifemastat; Etanerceft; Etebeneside; Interleukin-6; Leflunomide; Renerceft; Robenzaryt, rodellaben; M-5010; Parecoxib; Rofecoxib; RS-130830; S-2474; TSA-234; Valdecoxib.
[75] Anti-athering agents
[76] H-327 / 86; Mifobate; Rodozekar; Riboflavin butyrate; Timmefuron.
[77] Bacteriostatic
[78] Acesadone; Acetosulfone sodium; Alamesin; Alexidine; Amdinocillin; Amdinocillin coating chamber; Amicycline; Amifloxacin; Amifloxacin mesylate; Amikacin; Amikacin sulfate; Aminosalicylic acid; Aminosalicylate sodium; Amoxicillin; Ampomycin; Ampicillin; Ampicillin sodium; Apalcillin sodium; Apramycin; Aspartosine; Astromycin sulfate; Abilamycin; Aboparcin; Azithromycin; Azolocillin; Azolocillin sodium; Bacampicillin hydrochloride; Bacitracin; Bacitracin methylene disalicylate; Bacitracin jin; Bambermycin; Benzoylpas calcium; Verithromycin; Betamycin sulfate; Viapenem; Biniramycin; Biphenamine hydrochloride; Bispyrithione magsulpex; Butikacin; Butyrosine sulfate; Capreomycin sulfate; Carbadox; Carbenicillin disodium; Carbenicillin indanyl sodium; Carbenicillin phenyl sodium; Carbenicillin; Carumanodium sodium; Sephachlor; Cepadroxyl; Sefamandol; Sephamandol Naphate; Cefamandol sodium; Cefaparol; Sephatrizin; Cefazaflu sodium; Cefazoline; Cefazoline sodium; Cefebuperazone; Ceftinir; Cefepime; Cefepime; Cefetechol; Sepiksim; Ceftmenoxime; Cefmetazole; Ceftmethazole sodium; Cytoniside monosodium; Cytoniside sodium; Cepharazone sodium; Celandide; Cytotaxic sodium; Cetetane; Cetetane disodium; Cell thyroid cancer; Sepoxycitin; Sepoxithin sodium; Ceftimizol; Cefepimisol sodium; Ceftyramide; Ceftyramide sodium; Ceftyromium sulfate; Cefpodoxime proxetyl; Ceftrozil; Ceproxadine; Ceftsulodine sodium; Ceftazidime; Ceftutibutene; Ceftizone sodium; Ceftriaxone sodium; Cefuroxime; Cefuroxime axetyl; Cefuroxime coated cetyl; Cefuroxime sodium; Cephacetyl sodium; Cephalexin; Cephalexin; Cephaloglycine; Cephaloridine; Cephalotin sodium; Cefapirine sodium; Cepradine; Cetocycline; Cetophenicol; Chloramphenicol; Chloramphenicol palmitate; Chloramphenicol pantothenate complexes; Chloramphenicol sodium succinate; Chlorhexidine phosphanilate; Chloroxylenol; Chlortetracycline bisulfate; Chlortetracycline; Synoxacin; Ciprofloxacin; Ciprofloxacin; Sirolemycin; Clarithromycin; Clinafloxacin; Clindamycin; Clindamycin; Clindamycin palmitate; Clindamycin phosphate; Clofazimin; Cloxacillin benzatin; Xaxacillin sodium; Clock sequence; Collimethate sodium; Colistin sulfate; Cumermycin; Cumermycin sodium; Cyclacillin; Cycloserine; Dalfopristin; Answer loss; Daptomycin; Demeclocycline; Demeclocycline; Demecycline; Deno rubella; Diaberridine; Dicloxacillin; Dicloxacillin sodium; Dihydrostreptomycin sulfate; Dipyrithione; Dirithromycin; Doxycycline; Doxycycline calcium; Doxycycline phosphattex; Doxycycline cyclate; Droxacin sodium; Enoxacin; Epicillin; Epitetracycline; Erythromycin; Erythromycin architrate; Erythromycin estholate; Erythromycin ethyl succinate; Erythromycin glucetate; Erythromycin lactobionate; Erythromycin propionate; Erythromycin stearate; Ethambutol; Ethionamide; Fleoxacin; Floxacillin; Fludalanine; Flumequin; Fosfomycin; Fosfomycin tromethamine; Fumoxicillin; Furazolium chloride; Furazolium tartrate; Pushdate sodium; Fusidic acid; Gentamicin sulfate; Glomomoam; Glamicidine; Haloprogin; Hetacillin; Hetacillin; Hexadine; Ibafloxacin; Imipenem; Isoconazole; Isepamicin; Isoniazid; Probemycin; Kanamycin sulfate; Chitasamycin; Lebofuraltadon; Revpropylsilin; Rextromycin; Lincomycin; Lincomycin; Romefloxacin; Romefloxacin; Romefloxacin mesylate; Loracarbef; Mapfenide; Meclocycline; Meclocycline sulfosalicylate; Megalomycin phosphate; Mequidox; Meropenem; Metacycline; Metacycline; Methenamin; Methenamin hypofurate; Methenamin mandelate; Methicillin sodium; Metioprim; Metronidazole; Metronidazole phosphate; Mezlocillin; Meziocillin sodium; Minocycline; Minocycline; Mircamycin; Monensin; Monensin sodium; Naphcillin sodium; Nalidixate sodium; Nalidixic acid; Natamycin; Nebramycin; Neomycin palmitate; Neomycin sulfate; Neomycin undecylenate; Netylmycin sulfate; Neutramycin; Nipuiraden; Nifuraldezone; Nipuratle; Nifuratron; Nipurazil; Nipurimide; Nipiupyrinol; Nipurquinazole; Nipurthiazole; Nitrocycline; Nitrofurantoin; Nitromide; Norfloxacin; Novobioxin sodium; Oploxacin; Onnetoprim; Oxacillin sodium; Oxymonam; Oxymonam sodium; Oxolinic acid; Oxytetracycline; Oxytetracycline calcium; Oxytetracycline; Palmidicin; Parachlorophenol; Paulomycin; Pefloxacin; Pefloxacin mesylate; Phenamecillin; Penicillin G benzatin; Penicillin G; Penicillin G procaine; Penicillin G sodium; Penicillin V; Penicillin V benzatin; Penicillin V hydravamin; Penicillin V; Pentagedon sodium; Phenyl aminosalicylate; Piperacillin sodium; Pirbenicillin sodium; Pyridycillin sodium; Pyrimycin; Pibampicillin; Pibampicillin pamoate; Pibampicillin probenate; Polymyxin B sulfate; Porphyromycin; Propicacin; Pyrazinamide; Pyrithione zinc; Quindecamine acetate; Quinupristin; Racefenicol; Lamoplanin; Ranimycin; Lelomycin; Repromycin; Lipabutin; Rifamethane; Lipamexyl; Lipamide; Rifampin; Ripapentin; Rifaximin; Lolitetracycline; Rolitetracycline nitrate; Rosamycin; Rosaramicin butyrate; Rosaramicin propionate; Rosaramicin sodium phosphate; Rosaramicin stearate; Rojosacin; Loxarson; Roxytromycin; Acid cyclins; Sanpetrinem sodium; Sarmoxicillin; Sarpicillin; Scofafungin; Sisomycin; Sisomycin sulfate; Sparfloxacin; Spectinomycin; Spiramycin; Stalymycin; Stepymycin; Streptomycin sulfate; Streptonicozides; Sulfabenz; Sulfabenzamide; Sulfacetamides; Sulfacetamide sodium; Sulfacithin; Sulfadiazine; Sulfadiazine sodium; Sulfadoxin; Sulfalene; Sulfamerazine; Sulfameters; Sulfamethazine; Sulfamethazole; Sulfamethoxazole; Sulfamomonotoxins; Sulfamoxol; Sulfanilate zinc; Sulfanitran; Sulfasalazine; Sulfasomiazole; Sulfatiazoles; Sulfazamet; Sulfisoxazole; Sulfisoxazole acetyl; Sulfisxazole diolamine; Sulfomycin; Sulfopenem; Sulfacillin; Suncillin sodium; Talampicillin; Teicoplanin; Temefloxacin; Temocillin; Tetracycline; Tetracycline; Tetracycline phosphate complexes; Tetroxoprim; Thiamphenicol; Thifencillin; Ticarcillin cresyl sodium; Ticarcillin disodium; Ticarcillin monosodium; Ticlatone; Thiodonium chloride; Tobramycin; Tobramycin sulfate; Tosulfloxacin; Trimetapririm; Trimetaprim sulfate; Trisulfarimidine; Troleandomycin; Tropectomycin sulfate; Tyrotricin; Vancomycin; Vancomycin; Virginiamycin; Zorbamycin.
[79] Anticholinergic
[80] Alberine citrate; Anisotropin methyl bromide; Atropine; Atropine oxide; Atropine sulfate; Belladonna; Benafrizine; Benzetimide; Benzylonium bromide; Biferriden; Biferriden; Biperdene lactate; Clidinium bromide; Cyclopentolate; Dexetamide; Dicyclomine; Dihexiberin; Domazoline fumarate; Elantrin; Elucine; Etibenztropin; Eukartropin; Glycopyrrolate; Heteronium bromide; Homatropin hydrobromide; Homatropin methylbromide; Biocysiamine; Hisosamine amine hydrobromide; Hisosamine amine sulfate; Isopropamide iodide; Mefenzolate bromide; Methylatropine nitrate; Metoquizine; Oxybutynin chloride; Parafenzolate bromide; Pentapiperidium methylsulfate; Fencarbamide; Fodine methylsulfate; Proglumide; Propantelin bromide; Propenezolate; Scopolamine hydrobromide; Temotropium methylsulfate; Thyquinamide; Tophenasin; Toquizine; Triampyzine sulfate; Trihexifenidyl; Tropicamide.
[81] Anticoagulant
[82] Ankhrod; Ardeparin sodium; Vivalirudine; Brominedione; Dalteparin sodium; Decirudine; Dicumnarol; Heparin calcium; Heparin sodium; Liafolate sodium; Napamosat mesylate; Phenprocumon; Tinzaparin sodium; Warfarin sodium.
[83] Anticonvulsants
[84] Albutoin; Ameltolide; Atolide; Briamate; Carbamazepine; Pyromide; Cytenamide; Clonazepam; Cyheptamide; Dezinamide; Dimethadione; Devalproex sodium; Etherobarb; Etosuccinimide; Etotoin; Flulazepam; Fluzinamide; Phosphphenytoin sodium; Gabapentin; Eleptide; Lamotrigine; Magnesium sulfate; Mephenytoin; Mepobarbital; Methetoin; Metsuccinimide; Milacemide; Navazeenyl; Napimidone; Nitrazepam; Phenacemide; yellow jacket; Phenobarbital sodium; Pensuccinimide; Phenytoin; Phenytoin sodium; Primidone; Progabide; Ralitorrin; Remamide; Ropizin; Savelazole; Styripentol; Sultiam; Thiopental sodium; Tiletamine; Topiramate; Trimetadione; Valproate sodium; Valproic acid; Vigabatrin; Zoniclesol; Johnny'samide.
[85] Antidepressant
[86] Adatanserine; Adinazolam; Adinazolam mesylate; Allaproclate; Alletamine; Amederine; Amitriptyline; Amoxapine; Aftazapine maleate; Azalox fumarate; Azepindol; Azipramine; Bifenamol; Bupropion; Butacetin; Butriftyline; Caroxazone; Cartazolate; Cyclazindol; Cydoxepin; Cilobamin mesylate; Clodazone; Clomipramine; Cotinine fumarate; Cyclindol; Sifenamine; Cyprolidol; Ciproxamide; Daledarin tosylate; Dapoxetine; Dazadrol maleate; Dazepinyl; Desipramine; Dexamisol; Deximaphene; Dibenzepine; Dioxadol; Dothipine; Doxepin; Duloxetine; Eclanamine maleate; Encipherate; Etoferidone; Pantridone; Fehmethazole; Penmetramide; Pezolamine fumarate; Fluorracene; Fluoxetine; Fluoxetine; Fluparoxane; Gamma pexin; Guanoxyphene sulfate; Imaphene; Amyloxane; Imipramine; Indeloxazine; Intriptyline; Ifrindol; Isocarboxazide; Ketipramine fumarate; Lofepramine; Lortalamine; Mapprotilin; Mapprotilin; Malicracene; Milacemide; Minafrine; Mirtazapine; Moclobemide; Modal sulfate; Napaktadine; Napamethazole; Nefazodone; Nisoxetine; Nitrapudam; Nomifensin maleate; Nortriptyline; Octriptyline phosphate; Opipramol; Oxaprotiline; Oxyfertin; Paroxetine; Phenylazine sulfate; Pyrandamine; Piezotiline; Pridepine; Prolinetan; Protriptiline; Quipazine maleate; Rolycirine; Ceproxetine; Sertraline; Sibutramine; Sulfides; Hydrotosol; Tamethalin; Tampramine fumarate; Tandamine; Tiazem; Tozalinone; Geocetin; Trazodone; Trebenzomine; Trimimipramine; Trimimipramine maleate; Venlafaxine; Bilox photography; Gimeldine; Zometapine.
[87] Antidiabetic agents
[88] Acetohexamide; Bimoclomol; BM-17.0249; Buformin; Butoxamine; Carbutamide; Centpiperalon; Chlorpropamide; Clomoxyl; Etoformin; Etomoxir; Fenbutamide; GI-262570; Glyamilide; Glybenclamide; Glybornuride; Glybutimine; Glycaramid; Glyceranyl sodium; Glyclazid; Glyconamide; Glycidamid; Glyflumide; Glimepiride; Glypalamide; Glipizide; Glycidone; Glysamide; Glycentide; Glycinamide; Glysolamide; Glyoxepifeed; Glucagon; Glyburide; Glybutthiazole; Glybuzol; Glyclopyramid; Glyccyclamide; Glychexamide; Glycidine sodium; Glyoctamid; Glyparamide; Glypinamide; Glyprothiazole; Glycobuzol; Heptolamid; HMR-1964; insulin; Insulin argin; Insulin aspart; Insulin dananath; Insulin depalan; Insulin detemir; Insulin glargine; Insulin person; Insulin human, isophan; Insulin human ginkgo; Insulin human gin, extenden; Insulin, isopan; Insulin lispro; Insulin, neutral; Insulin zinc; Insulin gin, extenden; Insulin zinc; Isaglidol; JTT-501; JTT-608; Mebenformin; Metahexamide; Metformin; Methyl palmoxylate; Metirapone; Midaglyzol; Mitiglinide; Nateglinide; NN-304; NVP-DPP-728; Palmoxylate sodium; PNU-106817; Frraminide; Proinsulin people; Seglytide acetate; Tibeglycene; Tipformin; Tolazamide; Tolbutamide; Tolpyramid;
[89] Aldose reductase inhibitor
[90] AD-5467; Alestatin; Siglitazone; Darglitazone; Englitazone sodium; Epalestat; Fidarestat; Imirestat; Linogliide; Linogliide; MCC-555; Minarestat; NZ-314; Pioglitazone; Pyroglilide; Fornalist; Sorbvinyl; Risarestat; Rosiglitazone; Tendamistat; Tolesart; Troglitazone; Genarestat; Jopolet.
[91] Alpha-glucosidase inhibitors
[92] Acarbose; Camigliose; Emiglytate; Englitazone; Miglitol; Moranoline; Bogly Bose.
[93] Governor
[94] Rolfamidine, Diphenoxylate (Lomotil), Metronidazole (Flagyl), Methylprednisolone (Medrol), Sulfasaldine.
[95] Antidiuretics
[96] Argipressin tannate; Desmopressin acetate; Refreshin.
[97] antidote
[98] Dimercaprol; Edroponium chloride; Pomepisol; Leucovorin calcium; Levoleukorine calcium; Methylene blue; Protamine sulfate.
[99] Antiemetic
[100] Allosetron; Batanopride; Bemesetron; Benzquinamide; Chlorpromazine; Chlorpromazine; Clevopride; Cyclizine; Dimenhydrinate; Diphenidol; Diphenidol; Diphenidol pamoate; Dolacetron mesylate; Domperidone; Dronabinol; Fludorex; Flumeridone; Galdansetron; Granistron; Granistron; Lurosetrone mesylate; Meclizin; Metoclopramide; Metopi margin; Ondansetron; Pancopride; Prochlorperazine; Prochlorperazine disylate; Prochlorperazine maleate; Promethazine; Thiethylperazine; Thiethylperazine maleate; Thiethylperazine maleate; Trimethobenzamide; Jacobride.
[101] Antiepileptic
[102] Pelbamate; Loreclesol; Tolga carbide.
[103] Antiestrogens (nonsteroidal)
[104] Clometheron; Delmadinone acetate; Napoxidine; Nitromiphene citrate; Raloxifene; Tamoxifen citrate; Toremifene citrate; Trioxyphene mesylate.
[105] Antifibrinolytics:
[106] Chamostat; Napamosat mesylate.
[107] Fungicides
[108] Acrisocin; Ambruticin; Amphotericin B; Azaconazole; Azaserine; Bashipungin; Biponazole; Biphenamine; Bispyrithione magsulpex; Butoconazole nitrate; Calcium undecylenate; Candicidine; Carball-puccicin; Chlordantoin; Cyclopyrox; Cyclopyroxolamine; Silopungin; Cyscoazole; Clotrimazole; Cuprimycin; Depungin; Dipyrthione; Doconazole; Echonasol; Echonasol nitrate; Enylconazole; Etona nitrate; Penticonazole nitrate; Philippines; Fluconazole; Flucitocin; Pungimycin; Griseofulvin; Hamycin; Isoconazole; Itraconazole; Calafungin; Ketoconazole; Romopizin; Lidimicin; Mepartricin; Myconazole; Myconazole nitrate; Monensin; Monensin sodium; Naphthypine; Neomycin undecylenate; Nipuratle; Nipurmeron; Nitralamine; Nystatin; Octanoic acid; Orconazole nitrate; Oxyconazole nitrate; Oxyfungin; Parconazole; Particin; Iodide; Prolonol; Pyrithione zinc; Pyrronitrin; Rutamycin; Sanguinarium chloride; Saperconazole; Scofafungin; Selenium sulfide; Cinefungin; Sulfonazole nitrate; Terbinafine; Terconazole; Thiram; Ticlatone; Thioconazole; Tocyclate; Tolindate; Tolnaftate; Triacetin; Triafungin; Undecylenic acid; Bilidofulvin; Zinc undecylenate; Zinoconazole.
[109] Glaucoma medication
[110] Alprenoxim; Colporcin; Dapiprazole; Dipiberine; Naboxate; Pilocarpine; Pimabin.
[111] Antihistamines
[112] Acrivastin; Antazoline phosphate; Astimazole; Azatadine maleate; Barmastine; Bromodiphenhydramine; Bromfenyramine maleate; Carbinoxamine maleate; Cetirizine; Chlorpheniramine maleate; Chlorpheniramine polystyrenex; Cinnarizine; Clemastine; Clemastine fumarate; Clociramine aceturate; Cycliamine maleate; Cyclizine; Ciproheptadine; Dexbromfenyramine maleate; Dexchlorpheniramine maleate; Dimethindene maleate; Diphenhydramine citrate; Diphenhydramnin; Dorastin; Doxylamine succinate; Evastin; Levocavastin; Loratadine; Sorry serine; Noverastin; Orfenadrin citrate; Pyrabrom; Pyrilamine maleate; Pyroxanine maleate; Locustine; Rotoxamine; Tajiphiline; Temelastin; Terpenadine; Tripelennamin citrate; Tripelennamin; Triprolidine; Zolamin.
[113] Lipid lowering agents
[114] Cholestyramine resins; Clofibrate; Cholestipol; Krillvastatin; Dalvastatin; Dextrothyroxine sodium; Fluvastatin sodium; Gemfibrozil; Recimivid; Lovastatin; Niacin; Pravastatin sodium; Probucol; Simvastatin; Tikeside; Senbusin; Acifran; Beloxamide; Bezafibrate; Boxydine; Butoxamine; Cetaben sodium; Cipropibrate; Gemcardiols; Halophenate; Lipid fibrate; Meglutol; Nafenopin; Pimetin; Theofibrate; Tvric acid; Trexolate.
[115] Antihypertensive
[116] Alfuzosin; Alipamide; Althiazide; Amiquinine; Amlodipine besylate; Amlodipine maleate; Anarytide acetate; Artiprocin maleate; Belfosdil; Bemitradine; Bendacalol mesylate; Bendroflumethiazide; Benzthiazide; Betaxolol; Betanidine sulfate; Bevantolol; Biclodil; Bisoprolol; Bisoprolol fumarate; Adrendolol; Volumecomide; Butiazide: candoxatril; Candoxatrilat; Captopril; Carvedilol; Seronapril; Chlorothiazide sodium; Cicletanin; Silazapril; Clonidine; Clonidine; Clopamide; Cyclopentthiazide; Cyclothiazide; Darodipine; Debrisoquin sulfate; Delapril; Diaphamide; Diazoxides; Direvalol; Diltiazem maleate; Ditechirene; Doxazosin mesylate; Ecadotril; Enalapril maleate; Enalapril; Enalkyrene; Endralazine mesylate; Epithiazide; Eprosartan; Eprosartan mesylate; Fenoldopam mesylate; Flavodilol maleate; Flordipine; Florcequinan; Fosinopril sodium; Pocinoprilat; Guanabenz; Guanabenz acetate; Guanacline sulfate; Guanadrel sulfate; Guancidine; Guanetidine monosulfate; Guanetidine sulfate; Guanfacin; Guanisoquin sulfate; Guanochlor sulfate; Guanotin; Guanoxabenz; Guanoxate sulfate; Guanoxyphen sulfate; Hydralazine; Hydralazine polystyrenex; Hydroflumethiazide; Indacrinone; Indamide; Indolaprif; Indolamin; Indolamin; Indorenate; Lacidipine; Lenniquinine; Rev chromacalim; Lisinopril; Ropecidine; Losartan; Rosulazin; Mebutamate; Mecamylamine; Medroxalol; Medroxalol; Metalthiazide; Methiclothiazide; Methyldopa; Methyl dopate; Metipranolol; Metolazone; Metoprolol fumarate; Metoprolol succinate; Metyrosine; Minoxidil; Monatefil maleate; Muzolimin; Nebivolol; Nirenedipine; Oponin; Pargiline; Faroside; Pelanserine; Perindopril erbumin; Phenoxybenzamine; Pinassidyl; Fibopril; Polythiazide; Prazosin; Primidolol; Prezidylol; Quinapril; Quinaprilat; Quinazosin; Quinellolan; Quinpyrrole; Quinuclium bromide; Ramipril; Lau olpia serpentina; Reserpin; Saprisartan; Saralacin acetate; Sodium nitroprusside; Sulfinolol; Tasosartan; Telluripine; Temocapryl; Terrazosin; Terlachiren; Thiamenidine; Thiamenidine; Ticlinafen; Tinabinol; Thiodazosin; Thifentocin; Trichlormethiazide; Trimazocin; Trimetaphan camsylate; Trimoxamine; Tripamide; Zipamide; Jankyren; Zofenoprilat arginine.
[117] Antihypertensive
[118] Cyclaprine; Midoderin.
[119] Anti-inflammatory
[120] Alclofenac; Alclomethasone dipropionate; Algston acetonide; Alpha amylase; Hints; Amsinapid; Amfenac Sodium; Amiprilos; Anakinra; Anirolact; Anitzafen; Apazone; Valsalazide disodium; Bendazac; Benoxapropene; Benzidamine; Bromelains; Broperamol; Budesonide; Carpropene; Cyclopropene; Syntazone; Cliprofen; Clobetazol propionate; Clobetason butyrate; Clopilac; Cloticasone propionate; Cormethasone acetate; Crotodoxone; Deplazacort; Desonide; Desoxymethasone; Dexamethasone dipropionate; Diclofenac; Diclofenac sodium; Diflorasone diacetate; Diflumidon sodium; Diflunisal; Difluprenate; Diphthalone; Dimethyl sulfoxide; Drocinonin; Endlison; Enlimab; Enolicam sodium; Epirisol; Etodolak; Etophenamate; Felbinac; Phenamol; Penbufen; Fenclofenac; Fenchlorac; Pen slaughter; Fenpipallon; Pentiazac; Flazalon; Fluazacort; Flufenamic acid; Flumizol; Flunisolide acetate; Flunicin; Flunicin meglumine; Fluorocortin butyl; Fluorometholone acetate; Fluquazone; Flurbiprofen; Fluretofen; Fluticasone propionate; Furapropene; Furobufen; Halogeninide; Halobetasol propionate; Halopredone acetate; Ibufenac; Ibuprofen; Ibuprofen aluminum; Ibuprofen piconol; Iloniadab; Indomethacin; Indomethacin sodium; Indopropene; Indosol; Intrazole; Isoflupredone acetate; Isozepak; Isoxiccam; Ketoprofen; Lofemizol; Lornoxicam; Ronazolac; Loteprednol ethanecarbonate; Meclofenamate sodium; Meclofenamic acid; Mechlorisone dibutyrate; Mefenamic acid; Mesalamine; Mececlazone; Methylprednisolone sulfeptanate; Momiflumate; Nabumetone; Naproxen; Naproxen sodium; Naproxol; Nimazone; Olsalazine sodium; Orgotane; Orphanoxine; Oxaprozin; Oxyphenbutazone; Paraniline; Pentosan polysulfate sodium; Fenbutazone sodium glycerate; Pirfenidone; Pyroxicam; Pyoxycampin cinnamate; Pyoxycham olamine; Pirprofen; Predazate; Furiprone; Prodolic acid; Proguazone; Proxazole; Proxazole citrate; Limexolone; Romanis; Salcholex; Salasedine; Salsalate; Sanguinarium chloride; Seclazone; Cermethasine; Sudoxicam; Sulindac; Suprofen; Tametacin; Talni flu mate; Thalosalate; Tebupelone; Tenidaf; Tenidaf sodium; Tenoxycam; Tesicam; Tesidide; Tetridamine; Thiopinac; Thixocortol pivalate; Tolmetin; Tolmetin sodium; Triclonide; Triflumidate; Mapmetacin; Zomepilac Sodium.
[121] Antimalarial
[122] Acedapson; Amodiaquine; Amquinate; Arteflene; Chloroquine; Chloroquine; Chloroquine phosphate; Cycloguanyl pamoate; Enpyrroline phosphate; Halophantrin; Hydroxychloroquine sulfate; Mefloquine; Menoxtone; Mircamycin; Primaquine phosphate; Pyrimethamine; Quinine sulfate; Tebuquin.
[123] disinfectant
[124] Aztreonam; Chlorhexidine gluconate; Imidurea; Risetamine; Nibroxane; Pyrazmonam sodium; Propionic acid; Pyrithione sodium; Sanguinarium chloride; Tigemonam dicholine.
[125] Antimigraine
[126] Almotriptan; Alniditan; Abitriptan; Azasetron; Azatadine; Bemesetron; BIBN-4096BS; BMS-181885; Bromocriptine; Dolacetron; Donittriptan; Evalzotan; Eletriptan; Ergotamine; Probatriptan; Ifprazochrome; IS-159; Risulide; Romerizine; LY-334370; LY-53857; Metagoline; Mettergotamine; Methiserguide; Naratriptan; ORG-GC-94; Oxetrone; Pipetiadene; Pizotifen; Propiserguide; Rizatriptan; Sergolexsol; Sumatriptan; Tropanserine; Tropoxin; UK-116044; Footboard; Jatosetron; Zolmitriptan.
[127] Active ingredients for the treatment of seasickness and vomiting
[128] Buclizine; Ciclizin lactate; Naboate.
[129] Cell proliferation inhibitor
[130] Ashibisin; Aclarubicin; Acodazole; Acronin; Adozelesin; Aldesleukin; Altretamine; Ambomycin; Amethanetron acetate; Aminoglutetimides; Amsacrine; Anastrozole; Anthracycin; Asparaginase; Asperrin; Azacytidine; Azethepa; Azotomycin; Batimastad; Benzodepa; Bicalutamide; Bisantrene; Bisnapid dimesylate; Bizelesin; Bleomycin sulfate; Brequinar sodium; Bropyrimin; Busulfan; Cocktinomycin; Calusosterone; Carracemide; Carbetimers; Carboplatin; Carmustine; Carrubicin; Carzelesin; Cedefingol; Chlorambucil; Sirolemycin; Cisplatin; Cladribine; Crisnatol mesylate; Cyclophosphamide; Cytarabine; Dacarbazine; Dactinomycin; Daunorubicin; Decitabine; Dexormaplatin; Dezaguanine; Dezaguanine mesylate; Diajikuon; Docetaxel; Doxorubicin; Doxorubicin; Droloxifene; Droloxyphene citrate; Dromostanolone propionate; Duazomycin; Edda trexate; Eflomitin; Elsammitrusin; Enroplatin; Enpromate; Epipropidine; Epirubicin; Erbulosol; Esorubicin; Esturamustine; Sodium stramustine phosphate; Ethanidazol; Ethiodide oil I 131; Etoposide; Etoposide phosphate; Etorine; Padrosol; Pazarabine; Fenretinide; Phloxuridine; Fludarabine phosphate; Fluorouracil; Flurocitabine; Phosquidone; Postriecin sodium; Gemcitabine; Gemcitabine; Gold Au 198; Hydroxyurea; Idarubicin; Ifosfamide; Monomorphine; Interferon alfa-2a; Interferon alpha-2b; Interferon alpha-n1; Interferon alpha-n3; Interferon beta-Ia; Interferon gamma-Ib; Ifoplatin; Irinotecan; Lanreotide acetate; Letrozole; Leuprolide acetate; Liarosol; Rometrexole sodium; Romustine; Roxanthrone; Masoprocol; Mytrancin; Mechlorethamine; Megestrol acetate; Melengestrol acetate; Melphalan; Menogaryl; Mercaptopurine; Methotrexate; Methotrexate sodium; Metoprin; Metaturdepa; Mythinamide; Mitocarcin; Mitochromen; Mitogiline; Mitomalcin; Mitomycin; Mitosper; Mitotan; Mitoxantrone; Mycophenolic acid; Nocodazole; Nogalamycin; Ormaplatin; OxySuran; Paclitaxel; Pegaspargasse; Peliomycin; Pentamustine; Pepplomycin sulfate; Perphosphamide; Fifobroman; Capulsulfan; Pyroxanthrone; Plicamycin; Florestane; Porphymer sodium; Porphyromycin; Prednismustine; Procarbazine; Puromycin; Puromycin; Pyrazopurin; Ribophrine; Rogletimide; Saffmegol; Safingol; Semustine; Simtragen; Sparfosate sodium; Spartomycin; Spirogermanium; Spiromostin; Spiroplatin; Streptonigrin; Streptozocin; Strontium chloride Sr 89; Sulofenur; Thalisomycin; Taxanes; Taxoid; Tecogallan sodium; Tegapur; Teloxanthrone; Temophorpine; Teniposide; Theroxylone; Testosterone; Thiamiprine; Thioguanine; Thiotepa; Thiazopurin; tyrapazamine; Topotecan; Toremifene citrate; Trestolone acetate; Trisiribin phosphate; Trimetrexate; Trimetrexate glucuronate; Tryptorelin; Tubulosol; Uracil mustard; Uredepa; Vapretide; Berteporphine; Vinblastine sulfate; Vincristine sulfate; Bindesin; Vindesine sulfate; Vinepidine sulfate; Vin glycinate sulfate; Vinurosin sulphate; Vinorelbine tartrate; Binrocidine sulfate; Vinzolidine sulfate; Borosol; Geniplatin; Ginostatin; Zorubicin.
[131] Active ingredients for combination therapy with cell proliferation inhibitors
[132] Imipramine and desipramine.
[133] Anti-Parkinson's formulation
[134] Benztropin mesylate; Biferriden; Biferriden; Biperdene lactate; Carmantadine; Siladopa; Dopamantine; Etopropazine; Lazabemide; Levodopa; Romethalin; Mopegiline; Naxagolides; Pareptide sulfate; Procclidine; Quintoran; Rofinirol; Selegiline; Tolcapone; Trihexifenidyl.
[135] Inverse linkage
[136] Diphenoxymide; Diphenoxine; Diphenoxylate; Fluperamide; Lidamidine; Loperamide; Maleamers; Nufenoxol; Faregoric.
[137] Antiproliferative active ingredients
[138] Pyritrexime isethionate.
[139] Antiprotozoal Active Ingredients
[140] Amodiaquine; Azanidazol; Chestnut azole; Carnidazole; Chlortetracycline bisulfate; Chlortetracycline; Flubendazole; Flunidazole; Halofuginone hydrobromide; Imidocarb; Ipronidazole; Metronidazole; Misnidazole; Moxnidazole; Nitarson; Particin; Puromycin; Puromycin; Rodinazole; Sulindazol; Tinidazole.
[141] Active ingredients for the treatment of itching
[142] Ciproheptadine; Metdilazine; Metdilazine; Trimetaprazine tartrate.
[143] Psoriasis active ingredient
[144] Acitretin; Anthraline; Azabin; Calcipotriene; Cycloheximide; Enazadrem phosphate; Etretinate; Liarosol fumarate; Lonaphalene; Tepoxaline.
[145] Neuroleptics
[146] Acetophenazine maleate; Allenemol hydrobromide; Alfertin; Azaferon; Batelapin maleate; Benperidol; Benzinepyrine; Brobsin; Bromperidol; Brom ferridol decanoate; Butaclamole; Butaperazine; Butaperazine maleate; Carfenazine maleate; Carbothroline; Chlorpromazine; Chlorpromazine; Chlorproticsen; Sinperene; Syntriamide; Clomacran phosphate; Clofenticol; Clopimozide; Clopipazan mesylate; Chloroferon; Clothiapine; Clotixamide maleate; Clozapine; Cyclophenazine; Dropperidol; Etazolate; Phenamide; Flucindol; Flumezapine; Flufenazine decanoate; Flufenazine enanthate; Flufenazine; Flupiferon; Flupyrrylene; Flutroline; Gebothroline; Halopemide; Haloperidol; Haloperidol decanoate; Iloperidon; Imidolin; Renferon; Mazafertin succinate; Buckthorn minced; Mesoridine besylate; Methiapine; Millenferon; Millipertin; Molindon; Naranol; Neflumozide; Ocaperidone; Olanzapine; Oxyferromide; Fenfluridol; Pentiapine maleate; Perphenazine; Fimozide; Pinoxepin; Fifamferon; Piperacetazine; Pipeothiazine phallitate; Piquindon; Prochlorperazine disylate; Prochlorperazine maleate; Pro margin; Lemokifride; Lemokifride; Lymazole; Ceperidol; Sertindol; Cetoferon; Spiferon; Thiolidazine; Thiolidazine; Thiotices; Thiotices; Thioperidone; Thiospyrone; Trifluoroperazine; Triple luperidol; Triplopromazine; Triplopromazine; Ziprasidone.
[147] Antirheumatic agents
[148] Oranopine; Aurothioglucose; Vindarit; Robenzaryt sodium; Phenylbutazone; Pyrazolac; Prinoamide tromethamine; Cefrillos.
[149] Antihypertensive Formulations
[150] Becantone; Hycantones; Lucanton; Niridazole; Oxamniquine; Pararosanirin pamoate; Teroxalen.
[151] Active ingredients for the treatment of seborrhea
[152] Chloroxine; Pyroxtone; Pyroxtone olamine; Resorcinol monoacetate.
[153] Antispasmodic inhibitor
[154] Stilnium iodide; Tizanidine.
[155] Antithrombotics
[156] Argatroban; Anagrelide; Vivalirudine; Dalteparin sodium; Domitroban; Daltrovan; Danafaroid sodium; Dazosibene; E-3040; Efegatran sulfate; Enoxaparin sodium; Ifetroban; Ifetroban sodium; KW-3635; LCB2853; Linotrovan; Mipitroban; NM-702; Picotamide; Ramatrobane; Lidogrel; S-1452; Samic sogrerel; Ceratodast; Sulthroban; Tervogrerel; Tinzaparin sodium; Tripfenagrel.
[157] Antitussive
[158] Benproperine; Benzonatate; Bibenzoium bromide; Brohexine; Butyrate citrate; Butamate; Clobutinol; Clopedanol; codeine; Codeine polystyrenex; Redox; Dextromethorphan; Dextromethorphan polystyrenex; Dihydrocodeine; Dimethoxanate; Drawpropidine; Drothebanol; Eprazinone; Ethyl dibutate; Pedrillate; Guaiate; Hydrocodone; Hydrocodone polystyrex; Iquindamine; Isoaminyl; Revrobropizin; Levopropoxyphene narcite; Medazomide; Meprotic sol; Moguisteine; Morphlophone; Nefinalone; Noscarpine; Femeride nitrate; Pentoxyberine; Polcodine; Picoferrin; Pipazate prenoxdiazine; Promolate; Saredutant; Sodium dibutate; Succimeric sulfate; Tebacon; Tifepidine; Vadocaine; Zippeprole.
[159] Antiulcer
[160] Stamin H2 antagonist
[161] BL-6271; BL-6341A; BMY-25368; BRL-28390; Cimetidine; Dalcotidine; Donetidine; Ebrotidine; Ethyntidine; Pamotidine; ICI-162846; Icotidine; IGN-2098; Isotyquimide; Laputidine; Ramtidine; Laboltidine; Lufitidine; Mifentidine; Niferotidine; Nizatidine; Osutidine; Oxmetidine; Dermatitis; Pipatidine; Lamyxotidine; Ranitidine; Ranitidine bismuth citrate; Ranitidine nitrate; Roxatidine; Supotidine; TAS; Thiotidine; Bentidine; WHR-2348; YM-14471; Zaltidine; Zorantidine.
[162] Proton pump inhibitor
[163] Disuprazole; Esomeprazole; FPL-65372-XX; H-335 / 25; H-405 / 02; HN-11203; IY-81149; Lansoprazole; Reminoprazole; Rucartamide; N-2220; NC-1300; Nepaprazole; Omeprazole; Pantoprazole; Pantoprazole sodium; Picartamide; Picoprazole; Fumaprazole; Rabeprazole; Sabiprazole; SCH-28080; SKF-95-601; SKF-96067; SKF-97574; T-330; T-776; Tenatoprazole; Upiprazole; YH-1885; YM-19020.
[164] Prostaglandins
[165] Arbaprosteel; Butafrost; Deprosteel; Dimethyldinoprostone; Dimoxa frost; Enisoprost; Enprosteel; Mexiprosteel; Microprostol; Nocloprost; Ornoprostill; Oxoprostol; Remiprostol; Lioprothyl; Rosaprostol; SC-30249; Spirprosteel; TEI-1226; Tiprostanide; Trimorphosteel;
[166] Other antiulcers
[167] Aceglutamide aluminum; AD-1308; Benesate; Benzotrift; Beperdium iodide; Bifemellan; BTM-1086; Cardexomer iodine; Setlaxate; CF-19415; CHINOIN-127; Darrenzepine; Deboxamemet; Detralpate; DH-6615; Dosmalate; Ekaba feed; Ekabet; Esaprazole; Espartophosphate; Gefanate; Irsogladine; KW-5805; Lactalate; Rozilurea; MAR-99; MCI-727; MDL-201034; Mezolidone; Morphartrate; Nolinium bromide; Nubenzepine; Octreotide; P-1100; Piperanine; Pyrenzepine; Flaunotol; Polar prezinc; Levamifeed; RGH-2961; Rispenzepine; Lotraxate; Cetifthilin; Siltenzepine; Sofalcon; Sucralate; Sucrose sulfate; Sulfoglycotides; Tellenezepine; Teniloxazine; Tefrenone; Thiopropamine; Tolimidone; Tritide; Trithiozin; Hydroxyfeed; UH-AH-37; Zolezepine; Zolimidine.
[168] Preparations for the treatment of urolithiasis
[169] Benzoic acid; Cysteamine; Cysteamine; Tricitrate.
[170] Virus proliferation inhibitor
[171] Abacarvir; Acemannan; Acyclovir; Adefovir; Allobudine; Albirsef Sudox; Atevirdine; Amantadine; Aranotin; Aryldon; Atevirdine; Abridine; BW-935-U83; Calanolide B; Sidofovir; Sifamphyline; Cytarabine; DAPD; Delavirdine; Decyclovir; Didanosine; Disoxalyl; DPC-083; Edoxsudine; Epavirens; Emivirine; Enbiladen; Enviroxime; Famciclovir; Pamotin; Piacitabine; Pialuridine; Fosallylate; Foscarnet sodium; Phosphorone sodium; Gancyclovir; GW-420867X; Idocuridine; Ketoxal; L-697661; Lamivudine; Robucavir; Memotin; Metisosazone; Nevirapine; NSC-678323; Fencyclovir; Pyridavir; Ribavirin; Rimantadine; S-1153; Saquinavir; Somantadine; Soribudine; Statolon; Stavudine; Deviralline; Thioctic acid; Tyloron; Trifluidine; Trovirdine; U93923; Valacyclovir; Vidarabine; Vidarabine; Vidarabine; Though Shim; Salcitabine; Zidobudine; Hearty.
[172] Active ingredient for the treatment of benign prostatic hyperplasia
[173] Alfuzosin; CEP-701; Doxazosin; Dutasteride; FK-143; Gl-231818; GYKI-16084; Levormeloxyphene; Pirfenidone; RS-97078; Tamsulosin; Cytoglusid.
[174] Active ingredients for the treatment of osteoporosis
[175] Alendronic acid; Butedronic acid; Clodronic acid; EB-1053; Etidronic acid; Ibandronic acid; Incadronic acid; Medronic acid; Minodronic acid; Neridronic acid; Olpadronic acid; Oxideronic acid; Pamidronic acid; Pyridonic acid; Ranelic acid; Risedronic acid; Tiludronic acid; YM-529; Zoledronic acid.
[176] Carbonic Anhydrase Inhibitor
[177] Acetazolamide; AL-4414A; Diclofenamide; Dorzolamide; Metazolamide; Sezolamide; Sulfocarbylates.
[178] Antiarrhythmics
[179] Abanokyl; ACC-9164; Acecinide; Actisomide; Adenosine; Azmalin; Alinidine; Almocalant; Alprafenone; Flax pollon; Ambasilide; Ameltolide; Amiodarone; Apridine; Apridine; Artilide; Asokinol; AWD-G-256; Azimilides; Bendrizine; Benrixate; Benzodioxin; Verlaphenone; Bertosamil; Avidisamide; Bisaramil; BRL-32042; Bucide; Buchromon; Bunaftin; Buquineran; Butobendine; Butoprozin; Capobenic acid; Carbiczocaine; Carcainium chloride; Carporide; Carotenide; Cercanide; Cybenzoline; Cyphenin; Ciprapamide; CL-284027; Chlamyrantant; Clopilium phosphate; CV-6402; CVT-510; Cyclobirobuksin-D, D230; Detazum bitartrate; Disobutamide; Dexotalol; Dioxadylol; Diprafenone; Disobutamide; Disopyramide; Dofetilide; Drobulin; Dronedarone; Doxycinide; E047 / 1; E-0747; E-4031; Edifolone; Emilium tosylate; Emopamil; Enkinide; Eproxinedine; Erocanide; Ersentilide; Pepromide; Flecanide; Fluzoferide; Galanilide; Glemanserine; Guapekanin; GYKI-23107; GYKI-38233; heptacaine; Hydroxyphenone; Ibutylide; Indecaid; Isopylide; Itrokinide; Ketokainol; L-702958; L-706000; Levocoseotidyl; Lorazmine; Lorcanide; Meobentin; Mexiletin; Milacide; Modecanide; Moracigin; Moxapridine; Murocanide; Nibentan; Nikanoprol; Nipecalant; Nopecide; Oxyramid; Paratrigin; Pentinides; Pentisomide; Physicinide; Pyrmenol; Pyrazamide; Prasmalium bitartrate; Pranolium chloride; Prepurolin; Procainamide; Propaphenone; Pyrinoline; Quinacinol; Quindonium Bromide; Quinidine; Rekainam; Lilozaron; Lysotilide; Ronifamil; Rophytoin; Sematide; Cynomenin; Solfecainol; Spartane; Styrokinide; Stovadine; SR-47063; Sulameserod; Urikinide; Teddysamyl; Tericalandant; Tyrasinazine; Tocanide; Tocifen; Transcanide; Trecetilide; Nephew.
[180] cardiac
[181] Acadecin; Acetyl digtoxin; Acetiidigoxin; Acrichelin; Actodizin; Adibendan; Amlinone; Amselamine; Arbutamine; Arpromidine; AWD-122-239; Bemoradan; Bucladesine; Butopamine; Carbazeran; Carporide; Carperidide; Carcaserin; CGS-13928C; Cilobradine; CK-2130; CK-2289; Colporcin; CV-6402; Denophamine; Deslanside; Dexlaonic acid; Digitalis; Digitoxins; Digoxin; Dobutamine; Dobutamine; Docarpamine; Domipizone; Dopexamine; Doridoscin; Doxaminol; DPI-201-106; Dragrazine; Enporide; Enoxymon; ER-21355; Evodiamine; Parifamil; FK-664; Phosphructose; FR-113453; FR-46171; Gapromidine; Taloxine; Zitoformate; JP-1-468; GP-1-531; GP-668; Heftaminol; Hygenamine; Ibopamine; Forehead; Indolidan; Isamoltan; Isomazole; Levasecarnin; Levdobutamine; Lebocymendan; Limaprost; Lincidomin; Lyxazinone; MCI-154; Meridinone; Meprossilin; Meribendan; Methyldigoxin; Milldronate; Milnonone; Myopazine; Mixidine; MS-857; Nanterinone; Neraminol; NKH-477; Allprinon; OPC-18750; Ortenzepar; Oxenicin; Perinone; Penzitoxins; Pentrinitrol; Peruboside; Pimovendan; Pyoxymone; Pyrcidomin; Pyrinoxodan; Prisotinol; Propionylcarnitine; Prossilaridine; Quaazinone; Quazodidine; Quindonium Bromide; Rhamnodizin; Levzinone; Saterinone; Siguazodan; Cymendan; Sulfazole; Tebetoside; Toborinone; Ubidecarenone; Besnarinone; VPA-985.
[182] Idam
[183] Alibendol; Azintamide; Boldin; Cyclic acid; Cinnamethic acid; Clanobutin; Dehydrocholic acid; Dibuprolol; Epomediol; Exciproben; Pebuprolol; Pencibutyrol; Phenifitol; Hexacitron; Hismecromon; Menbutone; Moquizone; Fiprozoline; Prozapine; Cyanide; Tenilidon; Terbuprolol; Tocampil; Trepibutone.
[184] Cholinergic preparations
[185] Aceclidine; Betanecol chloride; Carbacol; Demecarium bromide; Dexpanthenol; Ecothioate iodide; Isofluroate; Methacholine chloride; Neostigmine bromide; Neostigmine methylsulfate; Physostigmine; Physostigmine salicylate; Physostigmine sulfate; Pilocarpine; Pilocarpine; Pilocarpine nitrate; Pyridostigmine bromide.
[186] Cholinergic agonists
[187] Sanomerine; Sanomerine Tartrate.
[188] Cholinesterase inhibitors
[189] Acetohydroxysamic acid; DMPS; Amifenazole; Obidoxyl chloride; Pralidoxime chloride; Pralidox iodide; Pralidogsim mesylate.
[190] Coccidiosis
[191] Achromide; Amidapson; Amploririum; Arprinoside; Bitifazone; Bucuinolate; Cyadox; Clazuril; Clopidol; Decoquinate; Diclazuryl; Dinitolamide; Dean Seed; Halofuginone; Retrazuryl; Narashin; Nequinate; Nicarbazine; Nipur semizone; Ponazuryl; Proquinolate; Robenidine; Semduramicin; Surazuril; Sulfanitran; Thiazuryl; Tosulur.
[192] diuretic
[193] Acetazolamide; Acetothiazide; Alipamide; Altizide; Amanazine; Ambrophylline; Ambuside; Amylolides; Aminomethradine; Amisomethradine; Ampyrimine; Afaxiphylline; Azolimine; Azocemide; Bemethided; Bemitradine; Bendroflumethiazide; Benzamyl; Benzolamide; Benzthiazide; Benzylhydrochlorothiazide; Besulfamid; Besunide, broclinate; Bumetanide; Butizide; Canrenoic acid; Carmethidide; Chlorazanyl; Chlorothiazide; Chlorthalidone; Cicletanin; Clazolimin; Clopamide; Clolexsolone; CVT-124; Disylenone; Disulfamide; Etamiphylline; Ethacrynate sodium; Ethacrynic acid; Etophylline; Etozoline; Fenquizone; FK-352; FR-113453; Furosemide; Hydrochlorothiazide; Hydroflumethiazide; Indacrinone; Indamide; Isosorbide; KW-3902; Remidosul; Mannitol; Mebutizide; Mefruside; Metalthiazide; Metazolamide; Methiclothiazide; Meticran; Metolazone; Muzolimine; Niaboline; OPC-31260; Oxprenoate; Ozolinone; Paraflutizide; Fenflutizide; Pyretanide; Polythiazide; Canrenoate; Propazolamide; Prorenoate; Prorenone; Phytamine; Quincarbate; Quinetazone; RPH-2823; S-8666; Citalidone; Spironolactone; Spirorenone; Spiroxasone; SR-48692; Sulflamide; Sulcrisnat; Sulfocarbylates; Sulfosemide; Cermetide; Teclothiazide; Thiamizide; Thienic acid; Torsamide; Triamterene; Trichlormethiazide; Triloxine; Tripamide; TRK-820; Ularitide; Urea; Cipamide.
[194] External parasitic
[195] Carbaryl; Clidafidine; Cipermethrin; Eprinomectin; Fenclofos; Penvalerate; Ivermectin; Lindane; Moxidecin; Niflulidide; Fermethrin; Temefoss.
[196] Antiemetic
[197] Apomorphine.
[198] Enzyme inhibitor
[199] Acetohydroxysamic acid; Alestatin sodium; Aprotinin; Benazepril; Benazeprillat; Benurestad; Bromocriptine; Bromocriptine mesylate; Cilastatin sodium; Fluropamide; Liggotryl; Liggotryl mesylate; Revcycloserine; Ribenzapril; Pentopril; Pepstatin; Perindopril; Polygnate sodium; Sodium amylosulfate; sorbic acid; Spirapril; Spirapril; Taleranol; Teprotide; Tolpamide; Zofenopril Calcium.
[200] Estrogen
[201] Chlorotrianicene; Dienestrol; Diethylstilbestrol; Diethylstilbestrol diphosphate; Aquilin; Epimethrol; Estradiol; Estradiol cypionate; Estradiol enanthate; Estradiol undecylate; Estradiol valerate; Estrazinol hydrobromide; Estriol; Estrofurate; Estrogen, conjugated; Estrogens, esterified; Estrone; Estrophytate; Ethynyl estradiol; Fenestrel; Mestranol; Nirestriol; Quinestrol
[202] Fibrinolytic
[203] Acetic acid; Amedipase; Anistreplase; Aprotinin; Arsenic lactate; Brinasses; Brinolase; Chamostat; Fibrinolysine; Inikaron; Iquindamine; Nattokinase; Famitlase; Picotamide; Starflavin; Streptokinase; Taurine; Tizabrine; Tranexamic acid;
[204] Free radical scavenger
[205] Pegorgotane.
[206] Active ingredients
[207] Cisapride (Propulsid); Metoclopramide (Reglan); Biosciamine (Levsin).
[208] Glucocorticoids
[209] Acrosinoids; Alclomethasone; Algston acetonide; Hints; Amsinapid; Amcinononide; Amebucort; Amelomethasone; Beclomethasone dipropionate; Vendazacort; Betamethasone; Betamethasone acetate; Betamethasone benzoate; Betamethasone dipropionate; Betamethasone sodium phosphate; Betamethasone valerate; Budesonide; Butyxocorte; Butyxocort propionate; CGP-13774; Ciclesonide; Cyclomethasone; Cyprosinonide; Clobetasol; Clobetasol 17-propionate; Clobetason; Clocortolone acetate; Clocortolone pivalate; Cloprednol; Cloticasone; Cloticasone propionate; CMJ; Cormethasone; Corticotropin; Corticotropin; Corticotropin zinc hydroxide; Cortisone acetate; Cortisazole; Cortivazol; Deplazacort; Deprodon; Deprodon propionate; Descinolone acetonide; Desonide; Dexoxymethasone; Dexoxycortone; Dexamethasone; Dexamethasone acefurate; Dexamethasone sodium phosphate; Dexbudesonide; Dichlorisone; Dipulason; Diflucortolone; Diflucortolone pivalate; Difluprenate; Dimesone; Domofredate; Doxybetasol; Drocinonin; FSDCICM; Fluazacort; Fluchlorol acetonide; Fluchloronide; Fludrocortisone; Hydroxycortide; Flumetasone; Flumethasone pivalate; Flumoksonide; Flunisolide; Fluorocinolone acetonide; Fluorinide; Fluorocortin; Fluorocortin butyl; Fluorocortolone; Fluorocortolone caproate; Fluorometholone; Flufamesone; Fluperolone acetate; Flufreddene; Fluprednisolone; Fluprednisolone valerate; Fluandrenolide; Fluticasone; Fluticasone propionate; Formocortal; Gestonone caproate; GW-215864X; GW-250945; Halogeninide; Halocortolone; Halomethasone; Halopredone acetate; Hydrocortamate; Hydrocortisone; Hydrocortisone acetate; Hydrocortisone acenate; Hydrocortisone buterate; Hydrocortisone butyrate; Hydrocortisone enbutate; Hydrocortisone sodium phosphate; Hydrocortisone sodium succinate; Hydrocortisone valerate; Icometason enbutate; Isoflupredone; Isopridniden; Ytrosinonide; Rosicortolone; Rosicortolone disbate; Loteprednol ethanecarbonate; Marzipridone; Mechlorisone; Medridone; Meprednisone; Methylprednisolone; Methylprednisolone acetate; Methylprednisoloxime sodium phosphate; Methylprednisolone sodium succinate; Mometasone furoate; Naflocorte; Nibacortol; Nibazole; Paramethasone acetate; Predazate; Predazolin; Prednicarbate; Prednisolamate; Prednisolone; Prednisolone acetate; Prednisolone farnesylate; Prednisolone hemisuccinate; Prednisolone sodium phosphate; Prednisolone sodium succinate; Prednisolone tebutate; Prednisone; Prednylidene; Pregnenolone; Prednisbal; Prosnonide; Lesocortol; Limexolone; Lopleponide; TBI-PAB; Ticabeson propionate; Tamobesone; Tipredan; Thixocortol; Thixocortol pivalate; Tralonide; Triamcinolone; Triamcinolone acetonide; Triamcinolone acetonide sodium; Triamcinolone bentonide; Triamcinolone diacetate; Triamcinolone furonide; Triamcinolone hexacetonide; Triclonide; Ulovetasol.
[210] styptic
[211] Aminocaproic acid; Oxamarin; Sulmarin; Thrombin; Tranexarsan.
[212] hormone
[213] Diethylstilbestrol; Progesterone; 17-hydroxy progesterone; Methoxyprogesterone; Norgestrel; Noethinodrel; Estradiol; Megestrol; Noretin drone; Levonorgestrel; Ethynediol; Ethynyl estradiol; Mestranol; Estrone; Aquilin; 17-alpha-dihydroequiline; Aequenin; 17 alpha dihydroequilenin; 17-alpha estradiol; 17-beta-estradiol; Leuprolide (lupron); Glucagon; Testosterone; Clomiphene; One memopowder gonadotropin; Human chorionic gonadotropin; Uropolytropin; Bromocriptine; Gonadorelin; Luteinizing hormone releasing hormones and analogues; Gonadotropin; Danazol; Testosterone; Dehydroepiandrosterone; Androstenedione; Dihydroestosterone; Relaxine; Oxytoxins; Vasopressin; Polycoulostatin; Follicle regulatory protein; Gonadoctrinin; Oshite maturathione inhibitors; Insulin growth factor; Follicle stimulating hormone; Progesterone; Tamoxifen; Corticoline obin triptutate; Cosinetropin; Metoguest; Posterior pituitary; Ceractide acetate; Somalapor; Somatlem; Somatropin; Somenophor; Somidovov.
[214] HMG-CoA Reductase Inhibitor
[215] Lovastatin (Mevacor); Simvastatin (Zocor); Pravachol; Fluvasatin (Lescol).
[216] Immunomodulator
[217] Dimefranol acedobene; Imiquimod; Interferon beta-lb; Lysophylline; Mycophenolate mofetil; Prezatide Copper Acetate.
[218] Immunomodulators
[219] Azarol; Panetizol mesylate; Prentazole; Oxamisol; Ristianol phosphate; Thymopentin; Tilomisosol.
[220] Immunostimulant
[221] Roxoribin; Teseryukkin.
[222] Immunosuppressant
[223] Azathioprine; Azathioprine sodium; Cyclosporin; Daltrovan; Gusperimus trichloride; Sirolimus; Tacrolimus.
[224] Active ingredients for the treatment of erectile dysfunction
[225] Abanokyl; Alprostadil; Amlodipine; BMS-193884; Delegamine; Doxazosin, E-4010; Glycerol trinitrate; IC-351; Melanotan II; Minoxidil; Nitraguazone; Papaverine; Phenoxybenzamine; Prazosin; Quinellolan; Sildenafil; UK-114542; Urapidyl; Vardenafil; VIP; Yohimbine.
[226] LHRH antagonist
[227] Deslorelin; Goserelin; Hysterlin; Lutereline acetate; Naparelin acetate.
[228] Hepatoprotectants
[229] Malotylate.
[230] Lutein dissolution
[231] Phenprosterene.
[232] Cerebrotonics
[233] Allolacetam; Albamelanin; Not cetam; Afaxiphylline; Aftiganel; Azetyreline; Brovincarmine; Kebaracetam; Sebimeline; CI-844; CI-933; Demiracetam; Dimoxamine; Donepezil; Dupracetam; Edarabon; Ensaculin; Pasoracetam; FK-960; Gavestinel; Igmesin; Muracetam; IOS-11212; JTP-4819; KST-5410; Letefinim; Ligustigin; Linopyrdine; MCI-225; Milamelanin; MKC-231; NDD-094; Nebracetam; Nicoracetam; Nizophenone; ONO-1603; OP-2507; OPC-14117; Oxyracetam; Picamylone; Piracetam; Pyroxelate; Pyrglutargin; Pramiracetam; Pyritinol; Quillostigmine; Rivaminol; Rivastigmine; Roll giracetam; Saabcomelin; Saprophtherine; SIB-1553A; Civopyridine; Cifattrigin; SM-10888; SNK-882; SR-46559-A; Stacophylline; T-588; T-82; TAK-147; Talsaclidine; Tatyrrelin; Tamitinol; Tenylcetam; Vinconate; Vinpocetin; Xaliprodene; Sanomerine; YM-796; YM-900; Z-321; Geprosilon.
[234] Mucolytic
[235] Acetylcysteine; Adamexin; Ambroxol; Bencysteine; Brohexine; Brovanexin; Carbocysteine; Carthasteine; Cystinexin; Restain; Danostane; Dembrexin; Dominiodol; Erdostein; Erythromycin salasedine; Erythromycin tinophosphate; Guai mesal; IDB-1031; Isalstein; Letosteine; Messteine; Mesna; Maidsteine; Moguisteine; Neltenexin; Nesosteine; Omonastaine; Oxablexin; Preysteine; Salmisteine; Stepronin; Tasuldine; Taurostein; Telmessteine; Thiopronin.
[236] Pupil enlargement system
[237] Berephrine.
[238] Neuroprotective agents
[239] Dizocilpin maleate.
[240] NMDA antagonist
[241] ACPC; Aftiganel; BMY-14802; CGP-37849; CP-101606; Dizocilpin; EAA-090; Eliprodil; Pelbamate; FPL-12495; Givestinel; Harcoseride; HU-211; Ifenoxazone; L-695902; Ranisemin; Licostinel; Ligustigin; Midapotel; Milnacipran; Nebostinel; Remamide; Cellotel; Ceratodast; Spermidine; Spermine; UK-240255; ZD-9379.
[242] Non-hormonal steroid derivatives
[243] Pregnenolone Succinate.
[244] Uterine contractions
[245] Carbofrost; Carboprost methyl; Carboprost tromethamine; Dinofrost; Dinoprost tromethamine; Dinoprostone; Ergonobine maleate; Methene frost; Methylergonobin maleate; Oxytoxins; Spartane Sulfate.
[246] Plasminogen activator
[247] Alteplase; Urokinase.
[248] PAF antagonist
[249] Lexiphant.
[250] Flocculation inhibitor
[251] Acadecin; Verafrost; Veraprost sodium; Cyprostenium calcium; Itazigrel; Liparizin; Oxagrelate.
[252] Progestin
[253] Algston acetophenide; Amadinone acetate; Anageston acetate; Chlormadinone acetate; Cinchole; Clogestone acetate; Clomegestone acetate; Desogestrel; Dimethysterone; Diddrogesterone; Etineron; Ethinodiol diacetate; Etonegestrel; Flulogeston acetate; Gestaclones; Gustoden; Gestonone caproate; Guestlinone; Haloprogesterone; Hydroxyprogesterone caproate; Levonorgestrel; Linestrenol; Medrogestone; Hydroxyprogesterone acetate; Methinodiol diacetate; Noretin drone; Noretin drone acetate; Noretinodrel; Norgestimate; Norgestomer; Norgestrel; Oxogeston phenpropionate; Progesterone; Quingestanol acetate; Quingestrone; Tigestol.
[254] Prostate growth inhibitors
[255] Pentomon.
[256] Prothyroid stimulating hormone
[257] Protyreline.
[258] Mental agent
[259] Minafrin.
[260] Calcium regulator
[261] Alpha calcidol; Calcifediol; Calcipotriol; Calcitonin; Calcitriol; Dihydrotachisterol; Dosercalciferol; Palecalcitriol; Lexacalcitol; Moxacalcitol; Cecaliferol; Theocalcitol; Tacalcitol;
[262] Relaxant
[263] Adiphenin; Alcuronium chloride; Aminophylline; Azumolene sodium; Baclofen; Benzoxamine; Carisoprodol; Chlorphenesin carbamate; Chlor josazone; Synflumide; Cinnamedrin; Clodanolene; Cyclobenzaprine; Dantrolene; Dantrolene sodium; Phenalamide; Penny lipol; Phenoxylates; Flaboxate; Fletazepam; Flumetramide; -Flulazepam; Hexafluorenium bromide; Isomylamine; Lorbamate; Mebeberine; Mesufrin; Metaxalone; Metocarbamol; Meticene; Nafomin maleate; Nelezaprin maleate; Papaverine; Expoxolane; Quintolate; Ritodrine; Ritodrine; Rolodine; Theophylline sodium glycinate; Thifenamyl; Xylo balm.
[264] Scabies
[265] Amitraz; Crotamiton.
[266] Curing agent
[267] Clobenoside; Ethanolamine oleate; Anhydrous sodium; Olamine; Tribenoside.
[268] sedative
[269] Propio margin.
[270] Sleeping pills / sedatives
[271] Allobarbital; Allonimid; Alprazolam; Amobarbital sodium; Bentazepam; Brotizolam; Butabarbital; Butabarbital sodium; Butal slope; Capuride carbochloral; Chlorine betaine; Chloral hydrate; Chlordiazepoxide; Cloperidone; Chlorate; Ciprazepam; Dexclamol; Diazepam; Dichloralphenazone; Estazolam; Ethchlorbinol; Etomidate; Phenobom; Flunitrazepam; Phozepam; Glutetimide; Halazepam; Lormethzepam; Meclocualone; Meprobamate; Metaqualon; Midaflu; Paraaldehyde; Pentobarbital; Pentobarbital sodium; Perlapine; Prazepam; Quazpam; Reclazepam; Rolletamide; Secobarbital; Cecobarbital sodium; Suproclones; Thalidomide; Tracazolate; Trepipam maleate; Triazolam; Tricetamide; Triclophos sodium; Trimetazine; Uldazepam; Zaleplon; Zolazepam; Zolpidem tartrate.
[272] Selective Adenosine A1 Antagonist
[273] Afaxiphylline
[274] Serotonin antagonists
[275] Altanserine tartrate; Amerserguide; Ketanserine; Ritanserine, Tropanserine
[276] Serotonin inhibitors
[277] Sinanserine; Fenclonin; Ponazin mesylate; Xylamidine tosylate.
[278] irritant
[279] Amponelic acid; Amphetamine sulfate; Ampyzin sulfate; Arbutamine; Azabon; Caffeine; Ceruleide; Ceruleide diethylamine; Cisapride; Dazopride fumarate; Dextroamphetamine; Dextroamphetamine sulfate; Difluanine; Dimepline; Doxapram; Etriptamine acetate; Etamiban; Phenethyline; Fluvanylate; Fluorotyl; Histamine phosphate; Indrillin; Mefexamide; Methamphetamine hydrochloride; Methylphenidate; Pemoline; Pyrovalerone; Xsamoterol; Xamoterol fumarate.
[280] Inhibitor
[281] Ampflutisol; Coxskicin; Ostrich
[282] Active ingredients for the treatment of symptomatic multiple sclerosis
[283] Fampridine.
[284] Synergist
[285] Proadifen.
[286] Thyroid hormones
[287] Levothyroxine sodium; Lyothyronine sodium; Riotrix.
[288] Thyroid inhibitors
[289] Metiazole; Propithiouracil.
[290] Thyroid-like preparations
[291] Tiromedan.
[292] Neurostabilizer
[293] Bromazepam; Buspyrone; Chlordiazepoxide; Clazolam; Clovazam; Chlorazate dipotassium; Chlorazate monopotassium; Demoxepam; Dexmedetomidine; Enciprazine; Gepyron; Hydroxyphenamate; Hydroxyzine; Hydroxyzin pamoate; Ketazolam; Lorazepam; Lorzapon; Loxapine; Roxapin succinate; Medazepam; Nabilon; Nisobamate; Oxazepam; Pentabamate; Pyrenferon; Lipasepam; Lollyfurn; Sulazepam; Tashiamine; Temazepam; Tripruvazam; Tibamate; Valnocktamide.
[294] Preparations for the Treatment of Cerebral Ischemia
[295] Dextrorphan.
[296] Drugs for the treatment of Paget's disease
[297] Tiludronate disodium.
[298] Uric acid excretion accelerator
[299] Benzbromarone; Irtemazole; Probeneside; Sulfinpyrazone.
[300] Vasoconstrictor
[301] Andrenalon; Amideprin mesylate; Angiotensin amide; Capaminol; Silutazoline; Clonazoline; Corvadrin; Domazoline; Epinephrine; Epinephyl borate; Phenoxazolin; Indanazoline; Mefentermin; Methiserguide; Methizoline; Methrapazoline; Napazoline; Nemazoline; Oxedrine; Oxymethazolin; Phenamazoline; Phenylephrine; Phenylpropanolamine polystyrenex; Tepazoline; Tetrizoline; Tinazoline; Tramazoline; Xylometazoline.
[302] Vasodilators
[303] Alprostadil; Azachlorzin; Methane sulfate; Bepridil; Butericin; Cethiedyl citrate; Chromonear; Clonitrate; Diltiazem; Dipyridamole; Droprenylamine; Erytrityl tetranitrate; Felodipine; Flunarizine; Postedil; Hexobendine; Inositol niacinate; Ifroxamine; Isosorbide nitrate; Isosorbide mononitrate; Isoxsuprine; Lidofrazine; Mefenidyl; Mefenidyl fumarate; Mibepradil dihydrochloride; Myopazine; Mixidine; Napronyl oxalate; Nicardipine; Nisergoline; Nicorandil; Nicotinyl alcohol; Nifedipine; Nimodipine; Nisoldipine; Oxenicin; Oxprenolol; Pentaerythritol tetranitrate; Pentoxifylline; Pentrinitrol; Perhexillin maleate; Pindolol; Pyrcidomin; Prenylamine; Propatyl nitrate; Sulfoxidyl; Terodirine; Tipropidyl; Tolazoline; Xanthinol niacinate.
[304] Active Ingredients for Wound Healing
[305] Ersofermin.
[306] Xanthine oxidase inhibitor
[307] Allopurinol; Oxyfurinol.
[308] In a preferred embodiment of the invention, the active ingredient is a PDE (phosphodiesterase) inhibitor, particularly preferably a PDE 4 inhibitor, in particular N- (3,5-dichloropyrid-4-yl) -3-cyclopropyl Methoxy-4-difluoromethoxybenzamide (INN: roflumilast), its N-oxide or pharmacologically suitable salt of roflumilast or its N-oxide. N- (3,5-dichloropyrid-4-yl) -3-cyclopropylmethoxy-4-difluoromethoxybenzamide, pharmacologically suitable salts thereof and preparation of N-oxides thereof, phosphodiester The use of these compounds as terase (PDE) 4 inhibitors is described in international patent application WO095 / 01338. In a particularly preferred embodiment of the invention, the active ingredient is a phosphodiesterase (PDE) 3/4 inhibitor, in particular (-)-cis-9-ethoxy-8-methoxy-6- (4-diisopropyl Aminocarbonylphenyl) -2-methyl-1,2,3,4,4a, 10b-hexahydrobenzo [c] [1,6] naphthyridine (INN: fumapentrin). (-)-cis-9-ethoxy-8-methoxy-6- (4-diisopropylaminocarbonylphenyl) -2-methyl-1,2,3,4,4a, 10b-hexahydrobenzo [ c] Preparation of [1,6] naphthyridine and its pharmacologically suitable salts, the use of this compound as a phosphodiesterase (PDE) 3/4 inhibitor is described in International Patent Application No. W098 / 21208.
[309] The matrix of the invention is very suitable as a dosage form for the active ingredient from a type of substance known as a reversible H ⁺ , K ⁺ -ATPase inhibitor referred to as a reversible proton pump inhibitor or APA (acid pump antagonist). Reversible proton pump inhibitors or APAs are described, for example, in patent documents DE-A 3917232, EP-A-0399267, EP-A-0387821, JP-A-3031280, JP-A-2270873, EP-A-0308917, EP-A -0268989, EP-A-0228006, EP-A-0204285, EP-A-0165545, EP-A-0125756, EP-A-0120589, EP-A-0509974, DE-A 3622036, EP-A-0537532, EP-A-0535529, JP-A-3284686, JP-A-3284622, US-A-4,833,149, EP-A-0261912, WO-A-9114677, WO-A-9315055, WO-A-9315071, WO- A-9315056, WO-A-9312090, WO-A-9212969, WO-A-9118887, EP-A-0393926, EP-A-0307078, US-A-5,041,442, EP-A-0266890, WO-A- 9414795, EP-A-0264883, EP-A-0033094, EP-A-0259174, EP-A-0330485, WO-A-8900570, EP-A-0368158, WO-A-9117164, WO-A-9206979, WO-A-9312090, WO-A-9308190, US-A-5,665,730, DE-A 3011490, US-A-4,464,372, EP-A-0068378, WO-A-9424130, US-A-5,719,161, US-A -6,124,313, WO-A-9527714, WO-A-9617830, WO-A-9837080, WO-A-9955705, WO-A-9955706, WO-A-0010999, WO-A-0011000, in particular the document WO-A -9842707, WO-A-9854188, WO-A-0017200, WO-A-0026217 and WO-A-0063211, secreting gastric acid Quinoline, imidazo [1,2-a] pyridine, 7,8,9,10-tetrahydroimidazo [1,2-h] [1,7] naphthyridine or 7H-8,9- It is described in other patent documents relating to compounds having a dihydropyrano [2,3-c] imidazo [1,2-a] pyridine base structure.
[310] Examples of reversible proton pump inhibitors or APAs are particularly preferred as follows.
[311] AU-461 [2- [1- (2-methyl-4-methoxyphenyl) -6- (2,2,2-trifluoroethoxy) -2,3-dihydro-1H-pyrrolo [3 , 2-c] quinolin-4-ylamino] -1-ethanol],
[312] DBM-819 [3- [1- (4-methoxy-2-methylphenyl) -6-methyl-2,3-dihydro-1H-pyrrolo- [3, 2-c] quinolin-4-ylamino] -1-propanol],
[313] KR-60436 [2- [1- (4-methoxy-2-methylphenyl) -6- (trifluoromethoxy) -2,3-dihydro-1H-pyrrolo [3,2-c] quinoline-4 -Ylamino] ethanol],
[314] R-105266; YJA-20379-8 [(+)-1- [8-ethoxy-4-[(1 (R) -phenylethyl) amino] -1,7-naphthyridin-3-yl] -1-butanone] , 8- (2-methoxycarbonylamino-6-methylbenzylamino) -2,3-dimethylimidazo [1,2-a] pyridine, 3-hydroxymethyl-8- (2-methoxycarba Bonylamino-6-methylbenzylamino) -2-methylimidazo [1,2-a] pyridine, 3-hydroxymethyl-8- (2-methoxycarbonylamino-6-methylbenzyloxy) -2 -Methylimidazo [1,2-a] pyridine, 8- (2-methoxycarbonylamino-6-methylbenzyloxy) -2,3-dimethylimidazo [1,2-a] pyridine, 8 -(2-t-butoxycarbonylamino-6-methylbenzylamino) -2,3-dimethylimidazo [1,2-a] pyridine, 8- (2-t-butoxycarbonylamino-6 -Methylbenzyloxy) -2,3-dimethylimidazo [1,2-a] pyridine, 8- (2-ethoxycarbonylamino-6-methylbenzylamino) -2,3-dimethylimidazo [ 1,2-a] pyridine, 8- (2-isobutoxycarbonylamino-6-methylbenzylamino) -2,3-dimethylimidazo [1,2-a] pyridine, 8- (2-isopro Foxycar Bonylamino-6-methylbenzylamino) -2,3-dimethylimidazo [1,2-a] pyridine, 8- (2-t-butoxycarbonylamino-6-methylbenzylamino) -3-hydrate Hydroxymethyl-2-methylimidazo [1,2-a] pyridine, 8- (2-t-butoxycarbonylamino-6-methylbenzyloxy) -3-hydroxymethyl-2-methylimidazo [1,2-a] pyridine, 8- {2-[(2-methoxyethoxy) carbonylamino] -6-methylbenzyloxy} -2-methylimidazo [1,2-a] pyridine- 3-methanol, 8- {2-[(2-methoxyethoxy) carbonylamino] -6-methylbenzylamino} -2-methylimidazo [1,2-a] pyridine-3-methanol, 8 -{2-[(2-methoxyethoxy) carbonylamino] -6-methylbenzylamino} -2,3-dimethylimidazo [1,2-a] pyridine, 8- {2-[(2 -Methoxyethoxy) carbonylamino] -6-methylbenzyloxy} -2-methylimidazo [1,2-a] pyridine-3-methanol, 8- {2-[(2-methoxyethoxy ) Carbonylamino] -6-methylbenzyloxy} -2,3-dimethylimidazo [1,2-a] pyridine, 3-hydroxymethyl-2-methyl-8-benzyloxyimidazo [1,2 -a] blood Dine, 3-hydroxymethyl-2-trifluoromethyl-8-benzyloxyimidazo [1,2-a] pyridine, 1,2-dimethyl-3-cyanomethyl-8-benzyloxyimidazo [1 , 2-a] pyridine, 2-methyl-3-cyanomethyl-8-benzyloxyimidazo [1,2-a] pyridine, 3-butyryl-8-methoxy-4- (2-methylphenylamino) Quinoline, 3-butyryl-8-hydroxyethoxy-4- (2-methylphenylamino) quinoline, 3-hydroxymethyl-2-methyl-9-phenyl-7H-8,9-dihydropyrano [2 , 3-c] imidazo [1,2-a] pyridine, 3-hydroxymethyl-2-methyl-9- (4-fluorophenyl) -7H-8,9-dihydropyrano [2,3 -c] imidazo [1,2-a] pyridine, (+)-3-hydroxymethyl-2-methyl-9-phenyl-7H-8,9-dihydropyrano [2,3-c] imide Dazo [1,2-a] pyridine, (-)-3-hydroxymethyl-2-methyl-9-phenyl-7H-8,9-dihydropyrano [2,3-c] imidazo [1, 2-a] pyridine, 8- (2-ethyl-6-methylbenzylamino) -3- (hydroxymethyl) -2-methylimidazo [1,2-a] pyridine-6-carboxamide, N -(2-hydroxyethyl) -8- (2,6-dimethylbenzylamino)- 2,3-dimethylimidazo [1,2-a] pyridine-6-carboxamide, 8- (2-ethyl-6-methylbenzylamino) -2,3-dimethylimidazo [1,2- a] pyridine-6-carboxamide, 8- (2-ethyl-6-methylbenzylamino) -N, 2,3-trimethylimidazo [1,2-a] pyridine-6-carboxamide, 8 -(2,6-dimethylbenzylamino) -2,3-dimethylimidazo [1,2-a] pyridine-6-carboxamide, 8- (2-ethyl-4-fluoro-6-methylbenzyl Amino) -2,3-dimethylimidazo [1,2-a] pyridine-6-carboxamide, 8- (4-fluoro-2,6-dimethylbenzylamino) -2,3-dimethylimida Crude [1,2-a] pyridine-6-carboxamide, 8- (2,6-diethylbenzylamino) -2,3-dimethylimidazo [1,2-a] pyridine-6-carbox Amide, 8- (2-ethyl-6-methylbenzylamino) -N- (2-hydroxyethyl) -2,3-dimethylimidazo [1,2-a] pyridine-6-carboxamide, 8 -(2-ethyl-6-methylbenzylamino) -N- (2-methoxyethyl) -2,3-dimethylimidazo [1,2-a] pyridine-6-carboxamide, 8- (2 Ethyl-6-methylbenzyl No) -3- (hydroxymethyl) -2-methylimidazo [1,2-a] pyridine-6-carboxamide, N- (2-hydroxyethyl) -8- (2,6-dimethyl Benzylamino) -2,3-dimethylimidazo [1,2-a] pyridine-6-carboxamide, 8- (2-ethyl-6-methylbenzylamino) -2,3-dimethylimidazo [ 1,2-a] pyridine-6-carboxamide, 8- (2-ethyl-6-methylbenzylamino) -N, 2,3-trimethylimidazo [1,2-a] pyridine-6-carbox Voxamide, 8- (2,6-dimethylbenzylamino) -2,3-dimethylimidazo [1,2-a] pyridine-6-carboxamide, 8- (2-ethyl-4-fluoro- 6-methylbenzylamino) -2,3-dimethylimidazo [1,2-a] pyridine-6-carboxamide, 8- (4-fluoro-2,6-dimethylbenzylamino) -2,3 -Dimethylimidazo [1,2-a] pyridine-6-carboxamide, 8- (2,6-diethylbenzylamino) -2,3-dimethylimidazo [1,2-a] pyridine- 6-carboxamide, 8- (2-ethyl-6-methylbenzylamino) -N- (2-hydroxyethyl) -2,3-dimethylimidazo [1,2-a] pyridine-6-carr Voxamide and 8- (2 -Ethyl-6-methylbenzylamino) -N- (2-methoxyethyl) -2,3-dimethylimidazo [1,2-a] pyridine-6-carboxamide, and especially 7,8-di Hydroxy-2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydroimidazo [1,2-h] [1,7] naphthyridine, 7-hydroxy-2,3-dimethyl -9-phenyl-7,8,9,10-tetrahydroimidazo [1,2-h] [1,7] naphthyridine, 9- (2-chlorophenyl) -7-hydroxy-2,3- Dimethyl-7,8,9,10-tetrahydroimidazo [1,2-h] [1,7] naphthyridine, 9- (2,6-dichlorophenyl) -7-hydroxy-2,3-dimethyl -7,8,9,10-tetrahydroimidazo [1,2-h] [1,7] naphthyridine, 9- (2-trifluoromethylphenyl) -7-hydroxy-2,3-dimethyl- 7,8,9,10-tetrahydroimidazo [1,2-h] [1,7] naphthyridine, 8-hydroxy-2,3-dimethyl-9-phenyl-7,8,9,10- Tetrahydroimidazo [1,2-h] [1,7] naphthyridin-7-one, (8R, 9R) -3-formyl-8-hydroxy-2-methyl-7-oxo-9-phenyl -7,8,9,10-tetrahydroimidazo [1,2-h] [1,7] naphthyridine, (7R, 8R, 9R) -3-hydroxymethyl -7,8-dihydroxy-2-methyl-9-phenyl-7,8,9,10-tetrahydroimidazo [1,2-h] [1,7] naphthyridine, (7S, 8R, 9R ) -7,8-isopropylidenedioxy-2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydroimidazo [1,2-h] [1,7] naphthyridine, 8 , 9-trans-8-hydroxy-3-hydroxymethyl-2-methyl-9-phenyl-7H-8,9-dihydropyrano [2,3-c] imidazo [1,2-a] Pyridine, 8,9-cis-8-hydroxy-3-hydroxymethyl-2-methyl-9-phenyl-7H-8,9-dihydropyrano [2,3-c] imidazo [1,2 -a] pyridine, 8,9-trans-3-hydroxymethyl-8-methoxy-2-methyl-9-phenyl-7H-8,9-dihydropyrano [2,3-c] imidazo [ 1,2-a] pyridine, 8,9-cis-3-hydroxymethyl-8-methoxy-2-methyl-9-phenyl-7H-8,9-dihydropyrano [2,3-c] Imidazo [1,2-a] pyridine, 8,9-trans-8-ethoxy-3-hydroxymethyl-2-methyl-9-phenyl-7H-8,9-dihydropyrano [2,3 -c] imidazo [1,2-a] pyridine, 8-hydroxy-7-oxo-9-phenyl-2,3-dimethyl-7H-8,9-dihydropyrano [2,3-c] Imidazo [1,2-a] pyridine, 7,8-dich Hydroxy-9-phenyl-2,3-dimethyl-7H-8,9-dihydropyrano [2,3-c] imidazo [1,2-a] pyridine, 7-hydroxy-9-phenyl-2 , 3-dimethyl-7H-8,9-dihydropyrano [2,3-c] imidazo [1,2-a] pyridine, (7R, 8R, 9R) -2,3-dimethyl-8-hydride Roxy-7-methoxy-9-phenyl-7,8,9,10-tetrahydroimidazo [1,2-h]-[1,7] naphthyridine, (7S, 8S, 9S) -2,3 -Dimethyl-8-hydroxy-7-methoxy-9-phenyl-7,8,9,10-tetrahydroimidazo [1,2-h]-[1,7] naphthyridine, (7S, 8R, 9R) -2,3-dimethyl-8-hydroxy-7-methoxy-9-phenyl-7,8,9,10-tetrahydroimidazo [1,2-h]-[1,7] naphthyridine , (7R, 8S, 9S) -2,3-dimethyl-8-hydroxy-7-methoxy-9-phenyl-7,8,9,10-tetrahydroimidazo [1,2-h]-[ 1,7] naphthyridine, (7R, 8R, 9R) -2,3-dimethyl-7-ethoxy-8-hydroxy-9-phenyl-7,8,9,10-tetrahydroimidazo [1, 2-h]-[1,7] naphthyridine, (7S, 8R, 9R) -2,3-dimethyl-7-ethoxy-8-hydroxy-9-phenyl-7,8,9,10-tetra Hydroimidazo [1,2-h]-[1,7] naphthyridine, (7S, 8S, 9S) -2,3-dime Methyl-8-hydroxy-7- (2-methoxyethoxy) -9-phenyl-7,8,9,10-tetrahydroimidazo [1,2-h] [1,7] naphthyridine, ( 7S, 8R, 9R) -2,3-dimethyl-8-hydroxy-7- (2-methoxyethoxy) -9-phenyl-7,8,9,10-tetrahydroimidazo [1,2- h] [1,7] naphthyridine, (7R, 8S, 9S) -2,3-dimethyl-8-hydroxy-7- (2-methoxyethoxy) -9-phenyl-7,8,9, 10-tetrahydroimidazo [1,2-h] [1,7] naphthyridine, (7S, 8R, 9R) -2,3-dimethyl-8-hydroxy-9-phenyl-7- (2-pro Foxy) -7,8,9,10-tetrahydroimidazo [1,2-h] [1,7] naphthyridine, (7R, 8R, 9R) -2,3-dimethyl-7,8-dimethoxy -9-phenyl-7,8,9,10-tetrahydroimidazo [1,2-h] [1,7] naphthyridine, (7R, 8R, 9R) -2,3-dimethyl-8-hydroxy -7- (2-methylthioethyloxy) -9-phenyl-7,8,9,10-tetrahydroimidazo [1,2h] [1,7] naphthyridine, (7S, 8R, 9R) -2 , 3-dimethyl-8-hydroxy-7- (2-methylthioethyloxy) -9-phenyl-7,8,9,10-tetrahydroimidazo [1,2h] [1,7] naphthyridine, (7R, 8R, 9R) -2,3-dimethyl-8-hydroxy-7- (2- Tylsulfinylethoxy) -9-phenyl-7,8,9,10-tetrahydroimidazo [1,2-h] [1,7] naphthyridine, (7S, 8R, 9R) -2,3- Dimethyl-8-hydroxy-7- (2-methylsulfinylethoxy) -9-phenyl-7,8,9,10-tetrahydroimidazo [1,2-h] [1,7] naphthyridine, (7R, 8R, 9R) -2,3-Dimethyl-8-hydroxy-7- (ethylthio) -9-phenyl-7,8,9,10-tetrahydroimidazo [1,2-h] [ 1,7] naphthyridine, (7S, 8R, 9R) -2,3-dimethyl-8-hydroxy-7- (ethylthio) -9-phenyl-7,8,9,10-tetrahydroimidazo [ 1,2-h] [1,7] naphthyridine, (7R, 8R, 9R) -2,3-dimethyl-8-hydroxy-7- (2,2,2-trifluoroethoxy) -9 -Phenyl-7,8,9,10-tetrahydroimidazo [1,2-h] [1,7] naphthyridine and (7S, 8R, 9R) -2,3-dimethyl-8-hydroxy-7 -(2,2,2-trifluoroethoxy) -9-phenyl-7,8,9,10-tetrahydroimidazo [1,2-h] [1,7] naphthyridine, and in particular (7R , 8R, 9R) -2,3-dimethyl-7,8-dihydroxy-9-phenyl-7,8,9,10-tetrahydroimidazo [1,2-h] [1,7] naphthyridine And (7R, 8R, 9R) -2,3-dimethyl-8-hydrate Oxy-7- (2-methoxyethoxy) -9-phenyl-7,8,9,10-tetrahydroimidazo [1,2-h] [1,7] naphthyridine.
[315] The matrix of the invention is also very suitable as a dosage form for the active ingredient from a type of substance known as acid labile H ⁺ , K ⁺ -ATPase inhibitors, referred to as irreversible proton pump inhibitors. Acid labile proton pump inhibitors (H ⁺ / K ⁺ -ATPase inhibitors) that may be specifically mentioned for the purposes of the present invention are described, for example, in EP-A-0,005,129, EP-A-0,166,287, EP-A 0,174,726, EP- Substituted pyridin-2-ylmethylsulfinyl-1H-benzimidazole as described in A-0,184,322, EP-A-0,261,478 and EP-A-0,268,956. One which may be mentioned as preferred in this regard is 5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridinyl) methylsulfinyl] -1H-benzimidazole (INN: omeprazole) , 5-difluoromethoxy-2-[(3,4-dimethoxy-2-pyridinyl) -methylsulfinyl] -1H-benzimidazole (INN: pantoprazole), 2- [3-methyl- 4- (2,2,2-trifluoroethoxy) -2-pyridinyl) methylsulfinyl] -1H-benzimidazole (INN: lansoprazole) and 2-{[4- (3-methoxypropoxy ) -3-methylpyridin-2-yl] methylsulfinyl} -1H-benzimidazole (INN: rabeprazole). In addition, acid labile proton pump inhibitors such as substituted phenylmethylsulfinyl-1H-benzimidazole, cycloheptapyridin-9-ylsulfinyl-1H-benzimidazole or pyridin-2-ylmethylsulfinylthier Noimidazoles are disclosed in DE-A-35 31 487, EP-A-0 434 999 and EP-A-0 234 485, respectively. Examples thereof include 2- [2- (N-isobutyl-N-methylamino) benzylsulfinyl] benzimidazole (INN: reminoprazole) and 2- (4-methoxy-6,7,8,9 -Tetrahydro-5H-cyclohepta [b] pyridin-9-ylsulfinyl) -1H-benzimidazole (INN: nepaprazole) and the like. Acid labile proton pump inhibitors are chiral compounds. The term acid labile proton pump inhibitor includes both pure enantiomers of the acid labile proton pump inhibitor and mixtures in any mixing ratio. Examples of pure enantiomers are 5-methoxy-2-[(S)-[(4-methoxy-3,5-dimethyl-2-pyridinyl) methyl] sulfinyl] -1H-benzimidazole (INN: Esomeprazole) and (-) pantoprazole. In addition, the acid labile proton pump inhibitor is present as such or is preferably in the form of a salt with a base. Examples of salts with bases include sodium, potassium, magnesium or calcium salts. If the acid labile proton pump inhibitor is isolated in crystalline form, it may comprise a significant amount of solvent. In addition, the term acid labile proton pump inhibitor according to the invention denotes all solvates, in particular all hydrates of acid labile proton pump inhibitors and salts thereof. Hydrates of salts of these bases with acid labile proton pump inhibitors are disclosed, for example, in W091 / 19710. Particularly preferred examples of acid labile proton pump inhibitors include pantoprazole sodium sesquihydrate (= pantoprazole sodium × 1.5 H ₂ 0), (−)-pantoprazole sodium sesquihydrate, pantoprazole magnesium dihydrate, omeprazole Magnesium, omeprazole and esomeprazole.
[316] In another preferred embodiment of the invention, the active ingredient is a glucocorticosteroid, in particular ciclesonide.
[317] The active ingredient may be present in the formulations of the present invention in the form of a salt of the active ingredient, depending on the nature of the active ingredient. In particular, there may be mentioned pharmacologically suitable salts of inorganic and organic acids commonly used in pharmaceutical techniques. These on the one hand are for example acids, such as hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, acetic acid, citric acid, D-gluconic acid, benzoic acid, 2- (4-hydroxybenzoyl) benzoic acid, butyric acid, sulfosalicylic acid, Water-soluble and water-insoluble acid addition salts with maleic acid, lauric acid, malic acid, fumaric acid, succinic acid, oxalic acid, tartaric acid, embonic acid, stearic acid, toluene sulfonic acid, methanesulfonic acid or 3-hydroxy-2-naphthoic acid And acids are used to prepare salts in equimolar proportions or at different rates depending on whether the acid is monobasic or polybasic and which salt is required.
[318] On the other hand, salts with bases are also suitable. Examples of salts with bases include alkali metals (lithium, sodium, potassium) or calcium, aluminum, magnesium, titanium, ammonium, meglumine or guanidinium salts, and the base is in an equimolar ratio of content or at a different rate from that. Used to generate salts.
[319] Those skilled in the art will appreciate that the active ingredient and its salts may comprise various amounts of solvents, for example, if desired to be separated in crystalline form. Therefore, the active ingredient may be present in the preparations of the invention in the form of solvates, in particular hydrates, and in the form of solvates, in particular hydrates of the salts of the active ingredient.
[320] The active ingredient may also be a chiral compound. Therefore, pure enantiomers and mixtures thereof of the active ingredient in any mixing ratio may be present in the formulations of the present invention.
[321] Fatty alcohols are preferably linear, saturated or unsaturated primary C ₁₀ -C ₃₀ alcohols. Preferred linear primary C ₁₀ -C ₁₈ alcohols are preferred. Examples of fatty alcohols are cetyl alcohol, myristyl alcohol, lauryl alcohol or stearyl alcohol, with cetyl alcohol being preferred. It is also possible for the mixture of fatty alcohols to be present if necessary.
[322] Triglycerides are glycerols having three hydroxyl groups esterified with carboxylic acids. The carboxylic acid is preferably monovalent basic C ₈ -C ₂₂ carboxylic acid, preferably natural carboxylic acid. In this case, the carboxylic acids may be different or preferably the same. Examples thereof are tristearate, tripalmitate and, particularly preferably trimyristate, such triglycerides sold under the trade names Dynasan 118,116 and 114, respectively. In addition, if necessary, a mixture of triglycerides may be present.
[323] Fatty acid esters are esters of fatty acids and alcohols. In this case, the alcohol is preferably a straight saturated or unsaturated primary C ₁₀ -C ₃₀ alcohol, preferably C ₁₂ -C ₁₈ alcohol. The fatty acid is preferably a monovalent basic C ₈ -C ₂₂ carboxylic acid, in particular a C ₁₂ -C ₁₈ carboxylic acid, preferably a natural carboxylic acid. Preferred fatty acid esters according to the invention have a melting point higher than 30 ° C. Examples of such fatty acid esters include cetyl palmitate sold by Cutina® CP. It is also possible, if desired, to have a mixture of fatty acid esters.
[324] The solid paraffin is preferably paraffinum solidum (ceresin). Also, for example, ozokerite may be used. It is also possible to use mixtures if necessary.
[325] According to the invention partial glycerides are glycerols in which one or two hydroxyl groups are esterified by carboxylic acids. Carboxylic acids are preferably C ₈ -C ₂₂ monovalent basic carboxylic acids, including natural carboxylic acids, in particular stearic acid, palmitic acid and myristic acid. In this case, the carboxylic acids may be different or, preferably, the same. Examples thereof include glycerol monostearate, glycerol distearate and glycerol monopalmitate, glycerol dipalmitate and the like. It may also be present in a mixture of partial glycerides, if necessary.
[326] If necessary, the mixture in each active ingredient unit may contain one or more other pharmaceutically suitable excipients. Examples of such other suitable excipients include polymers, sterols and basic compounds in the case of acid labile active ingredients.
[327] Examples of polymers include povidones (eg, Kollidon® 17, 30 and 90, commercially available from BASF), vinylpyrrolidone / vinyl acetate copolymers and polyvinyl acetates. Other examples include cellulose ethers {such as methylcellulose, ethylcellulose [Ethocel®] and hydroxypropylmethylcellulose}, cellulose esters (such as cellulose acetate phthalate (CAP), cellulose acetate trimellitate (CAT), Hydroxypropylmethylcellulose phthalate (HP50 and HP55) or hydroxypropylmethylcellulose acetate succinate (HPMCAS)], methacrylic acid / methyl methacrylate copolymer or methacrylic acid / ethyl methacrylate copolymer [Eudragit (registered) Trademarks) l]. The polymer is preferably povidone or ethylcellulose. It is also possible to be present in the mixture of polymers if necessary. Appropriate polymers may also be added to affect, for example, the pharmaceutical properties of each active ingredient unit (eg delivery of the active ingredient). Particularly preferred polymers according to the invention are povidone or ethylcellulose.
[328] The sterols are preferably vegetable sterols or animal sterols. Examples of vegetable sterols include ergosterol, stigmasterol, cytosterol, brassicasterol and camphorsterol. Examples of animal sterols include cholesterol and lanosterol, and the like. It may also be present as a mixture of sterols, if necessary.
[329] Examples of suitable basic compounds include inorganic basic salts such as ammonium carbonate and sodium carbonate, salts of fatty acids such as sodium stearate, amines such as meglumine, diethylamine, triethylamine and TRIS (2-amino-2-hydroxy Methyl-1,3-propanediol) or fatty amines such as stearylamine and the like. Stearylamine and sodium stearate are preferred. The addition of a basic compound to the mixture in each unit produces a stable formulation in the case of acid labile active ingredients, preventing possible discoloration.
[330] The proportion of the active ingredient (% by weight) in the individual active ingredient units differs depending on the type of active ingredient, which is advantageously 0.01 to 90%. The proportion of the active ingredient is preferably 0.1 to 70%, particularly preferably 5 to 40%, in particular 10 to 20%. The proportion of fatty alcohols in the individual active ingredient units is 10 to 70%, preferably 20 to 70%, particularly preferably 20 to 60% and especially 30 to 60%. The proportion of triglycerides in the individual active ingredient units is advantageously 10 to 70%, preferably 20 to 70%, particularly preferably 20 to 60% and especially 30 to 60%. The proportion of partial glycerides in the individual active ingredient units is advantageously 10 to 70%, preferably 20 to 70%, particularly preferably 20 to 60% and especially 30 to 60%. The proportion of fatty acid esters in the individual active ingredient units is advantageously 10 to 70%, preferably 20 to 70%, particularly preferably 20 to 60% and especially 30 to 60%. The proportion of solid paraffin is advantageously 10 to 70%, preferably 20 to 60% and especially 30 to 60%. If polymers are present, the proportion of polymers in the individual active ingredient units is suitably 1 to 25%, preferably 1 to 10%, particularly preferably 5 to 10%. If sterols are present, the proportion of sterols is suitably 1 to 10%, preferably 1 to 5%. If a basic compound is present, the proportion of the basic compound is 0.05 to 5%, preferably 0.1 to 1%.
[331] Preferred individual active ingredient units of the invention consist of 2 to 70% active ingredient, 10 to 60% fatty alcohol, 10 to 60% solid paraffin and 1 to 15% polymer. More preferred individual active ingredient units of the present invention consist of 2 to 70% active ingredient, 10 to 60% triglycerides, 10 to 60% solid paraffin, 1 to 15% polymer. Other preferred active ingredient units of the present invention consist of 2 to 70% active ingredient, 10 to 60% fatty acid ester, 10 to 60% solid paraffin and 1 to 15% polymer.
[332] In one embodiment, the invention relates to a formulation wherein the active ingredient is substantially uniformly distributed in an excipient matrix consisting of a mixture of one or more solid paraffins, fatty alcohols, fatty acid esters and partial glycerides or triglycerides. Such preparations are preferably with 0.05 to 25% active ingredient, 10 to 70% solid paraffin, 5 to 80% fatty alcohol, 2 to 20% fatty acid ester and 5 to 80% triglyceride or partial glyceride It is preferable to make. Such preparations consist in particular of 0.1-20% active ingredient, 15-65% solid paraffin, 5-70% fatty alcohol, 2-15% fatty acid ester and 5-70% triglyceride or partial glyceride. Such preparations are particularly preferably 0.5-15% active ingredient, 15-60% solid paraffin, 5-50% fatty alcohol, 5-10% fatty acid ester and 10-50% triglyceride or partial glyceride Is done.
[333] In another embodiment, the invention relates to a formulation wherein the active ingredient is substantially uniformly dispersed in an excipient matrix consisting of at least one fatty alcohol with at least one excipient selected from the group of solid paraffins or polymers. The polymer is preferably ethylcellulose or povidone. Such formulations preferably consist of 0.05-25% active ingredient, 20-90% fatty alcohol, 10-80% solid paraffin and / or 0.05-2% ethylcellulose. Such preparations consist in particular of 0.1-20% of active ingredient, 25-80% fatty alcohol, 10-70% solid paraffin and / or 0.1-1.5% ethylcellulose. It is particularly preferred that such preparations consist of 0.5-15% active ingredient, 25-70% fatty alcohol, 10-60% solid paraffin and / or 0.2-1% ethylcellulose.
[334] For acid labile active ingredients, particularly for acid labile proton pump inhibitors, the preferred individual active ingredient units of the present invention are 2 to 70% active ingredient, 10 to 60% fatty alcohol, 10 to 60% solid paraffin, 1 to 15% polymer and 0.1-2% basic compound. More preferred individual active ingredient units of the present invention comprise 2 to 70% active ingredient, 10 to 60% triglyceride, 10 to 60% solid paraffin, 1 to 15% polymer and 0.1 to 2% basic compound. Is done. Other preferred individual active ingredient units of the invention are 2 to 70% active ingredient, 10 to 60% fatty acid ester, 10 to 60% solid paraffin, 1 to 15% polymer and 0.1 to 2% basic compound Is done. Particularly preferred individual active ingredient units of the invention are 5-40% active ingredient, 20-60% fatty alcohol, 10-60% solid paraffin, 1-15% polymer and 0.1-1% basic compound. Is done. Even more particularly preferred individual active ingredient units of the invention are 5-40% active ingredient, 20-60% triglycerides, 10-60% solid paraffin, 1-15% polymer and 0.1-1% basic compound Is done. Other particularly preferred individual active ingredient units of the invention are 5-40% active ingredient, 20-60% fatty acid ester, 10-60% solid paraffin, 1-15% polymer and 0.1-1% basic It consists of a compound.
[335] Examples of active ingredient units of the invention include 5-40% pantoprazole sodium sesquihydrate, 10-40% cetyl alcohol, 5-60% solid paraffin, 1-5% polymer and 0.1-0.2% Basic compounds. Further examples of active ingredient units of the invention include 5-40% pantoprazole sodium sesquihydrate, 10-40% glyceryl tripalmitate, 5-60% solid paraffin, 1-5% polymer and 0.1 to 0.2% of a basic compound. Other examples of active ingredient units of the invention include 5-40% pantoprazole sodium sesquihydrate, 10-40% glyceryl tripalmitate, 5-60% solid paraffin, 1-5% polymer and 0.1 to 0.2% of a basic compound. Other examples of active ingredient units of the invention include 10-20% pantoprazole sodium sesquihydrate, 20-40% triglycerides, 40-70% solid paraffin, 1-5% sterols and 0.05-0.1 % Basic compound.
[336] The individual active ingredient units can be produced, for example, by spray drying or, preferably, by spray solidification, in particular by spray prilling. Especially preferably, it is produced by a prill treatment, in particular by a vibration ruffle treatment.
[337] In the case of spray solidification or prill treatment, the matrix excipient is suitably liquefied into a melt. The active ingredient is dissolved or dispersed in such a solution and the resulting solution or dispersion is sprayed or, preferably, prilled in a suitable apparatus. Preference is given to using dispersions of the active ingredient in the excipient melts.
[338] Spray solidification is carried out by a method known per se. A detailed description of this technique can be found in P.B. Deasy, Microencapsulation and Related Drug Processes (1984).
[339] The individual active ingredient units are produced by solidification from the liquid phase by producing droplets by means of vibrating nozzles, stabilizing the droplets formed after stabilization and drying or cooling them in a suitable medium (preferably gaseous or liquid). Particularly preferred. Examples of suitable media may be cooling gas such as air or nitrogen. Processes of this type and thus devices are described in DE 27 25 924, EP 0 467 221, W099 / 33555 and WO00 / 24382.
[340] According to the present invention, it is particularly preferable to maintain the liquid phase flowing to the nozzle in the frill treatment step at a constant temperature. The solidification is preferably carried out by instant cooling in a suitable cooling medium. In addition, in the case of the prill treatment, the liquid flowing into the nozzle, the vibrating nozzle and the droplet formed by the prill treatment is preferably maintained at a constant temperature until its sphere shape is stabilized, and the solidification of the droplet after stabilization is a gaseous or liquid cooling medium. It is preferable to carry out instantaneously by cooling using. Suitable systems for prilling by vibrating nozzles are commercially available, for example, by Brace GmbH, Alchenau, Germany. By prilling using a vibrating nozzle, it is possible to obtain each active ingredient unit in the form of microspheres having a narrow single-mode particle size spectrum with a particle size of 50 μm to 2 mm. The narrow monomodal particle size spectrum and the uniform spherical shape of the microspheres obtained in this way are characterized by a uniformly smooth surface, homogeneous and compartmentalized delivery of the active ingredient, and in the case of oral dosage forms (small particles It is expected to yield a solution-like behavior. In particular, the microspheres of the present invention are characterized by high stability, release of the active ingredient which can be controlled by the composition and particle size of the matrix, good flow properties, good compressibility and uniform delivery of the active ingredient. In particular, such microspheres are valuable in that they may not lose some functionality (eg, taste masking, resistance to gastric juice, delay in release) even when further treated with a plurality of pharmaceutical dosage forms.
[341] The microspheres are preferably monomodal microspheres having a particle size of 50 to 800 μm, preferably 50 to 500 μm, particularly preferably 50 to 400 μm, especially 50 to 200 μm.
[342] The particle size of the active ingredient used for spray drying or spray solidification, prilling or vibrating prilling is advantageously below 100 μm, in particular below 40 μm. The particle size is preferably 1 to 20 µm, particularly preferably 3 to 15 µm. Such particle size can be obtained, for example, by grinding the active ingredient in a suitable mill.
[343] The individual active ingredient units (formulations) of the invention can then be used as the basis for producing the dosage form of the invention. Examples of dosage forms obtainable by treating the formulations of the invention include suspensions, gels, tablets, coated tablets, multicomponent tablets, foamable tablets, rapid disintegrating tablets, powders in vesicles, coated tablets, capsules, solutions or other There are suppositories. Preferred dosage forms in this regard are oral formulations, in particular tablets. Particular preference is given to rapid disintegrating tablets and foamable tablets. Suitable excipients for a given dosage form are known to those of ordinary skill in the art. For oral dosage forms, it may surprisingly be formulated with an enteric coating.
[344] In the case of rapid disintegrating tablets, particularly suitable excipients are those which cause rapid disintegration of the tablet upon oral ingestion of the tablet. The excipient of the tablet which causes rapid disintegration of the tablet upon oral ingestion of the tablet preferably comprises at least one substance selected from the group of fillers and disintegrants. Preferably one or more other excipients from the group of lubricants, perfumes, flavoring substances and surfactant ingredients are present in the rapid disintegrating dosage form of the present invention. If necessary, a binder may be present. The rapid disintegrating dosage form preferably comprises at least one filler, at least one disintegrant and at least one glidant. Suitable fillers according to the invention are in particular basic basic fillers such as calcium carbonate [e.g. MagGran® CC or Destab® 95] and sodium carbonate, sugar alcohols such as mannitol [e.g. Pearlitol® or Parteck M], sorbitol [e.g., Karion®], xylitol or maltitol, starch such as corn starch, potato starch and wheat starch, microcrystalline cellulose, sugars such as glucose, lactose, levulose, sucrose And dextrose and the like. In a preferred development of the invention, the rapid disintegrating dosage form of the invention comprises as a filler a mixture of basic fillers (particularly calcium carbonate) and sugar alcohols (particularly sorbitol or mannitol). Suitable disintegrants according to the invention are in particular starch capable of performing the functions of insoluble polyvinylpyrrolidone (insoluble PVP, crospovidone), sodium carboxymethyl starch, sodium carboxymethylcellulose, alginic acid and disintegrant (e.g. starch 1500 )to be. Suitable examples of glidants include sodium stearyl fumarate, magnesium stearate, calcium stearate, stearic acid, talc and highly dispersed silica (Aerosil). Suitable examples of surfactant components include sodium lauryl sulfate or Tween® 20, 60 or 80, and the like. Examples of binders according to the invention include polyvinylpyrrolidone [PVP, Polyvidon® K25, 90] or polyvinyl acetate [eg, Kollidon® 64], gelatin, corn starch slime, pre-expanded Starch (starch 1500), hydroxypropylmethylcellulose (HPMC) or a mixture of hydroxypropylcellulose (L-HPC) and PVP.
[345] The proportion of fillers in the rapid disintegrating tablets (% by weight based on the final tablets) is advantageously between 1 and 99% by weight. The proportion of the filler is preferably 30 to 95% by weight, particularly preferably 60 to 85% by weight.
[346] The proportion of disintegrants in the rapid disintegrating tablets (% by weight based on the final tablets) is usually 1 to 30% by weight. It is preferable that the ratio of a disintegrant is 2-15 weight%. The proportion of disintegrant is particularly preferably 5 to 10% by weight.
[347] The proportion of glidants (weight percent based on the final tablet) in rapid disintegrating tablets is typically 0.1 to 5 percent by weight. It is preferable that the ratio of a lubricant is 0.3-3 weight%. It is especially preferable that the ratio of the lubricant is 0.5 to 2% by weight.
[348] The proportion of the individual active ingredient units (% by weight based on the final tablet) in the rapid disintegrating tablet is usually preferably 1 to 90% by weight. The proportion of the individual active ingredient units is preferably 70% by weight or less, in particular 10 to 50% by weight. As for the ratio, 15-25 weight% is especially preferable.
[349] The proportion of binder (% by weight based on the final tablet) is 10% by weight or less, preferably 5% by weight or less.
[350] If desired, one or more flavoring substances (eg, flavoring or sweetening agents) may additionally be present in the rapid disintegrating tablet. This may, for example, improve the taste of rapid disintegrating tablets. Such materials are added in conventional contents.
[351] Rapid disintegration tablets are produced by processes known to those skilled in the art. Rapid disintegrating tablets may comprise i) dry mixing of fillers and / or disintegrants; ii) production of granules of filler and binder and mixing of granules and disintegrants, or iii) dry granulation (briquetting or compression) of one or more excipient components.
[352] The individual active ingredient units are then mixed into the mixture obtained in i), ii) or iii), and then the perfume / flavor material and finally one or more lubricants, if necessary. The mixture obtained in this way can be compressed in a tablet press under normal conditions.
[353] According to the present invention, rapid disintegration of tablets means that tablets disintegrate within about 60 seconds when treated with disintegration test as described in European Pharmacopoeia (3nd edition, 1997) 2.9.1 Disintegration Time of Tablets and Capsules. do.
[354] In the case of solutions and suspensions, suitable excipients are in particular the excipients conventionally used to produce solutions or suspensions. Particularly suitable according to the invention are excipients, such as thickeners, which can produce a concentrated base. Examples of thickeners of the present invention include xanthan, substituted cellulose, polyvinylpyrrolidone (polyvidone type), sheet silicates, alginates or alginic acids and the like. Also, if necessary, mixtures of two or more different thickeners are possible. The proportion of thickeners depends upon the desired viscosity or concentration in the solution or suspension ready for use. Particular preference is given to solutions or suspensions having a viscosity of less than 500 mPa · s (measured with a rotary viscometer). The proportion of xanthan based on the solution or suspension ready for use is typically 0.1 to 1% by weight. The proportion of substituted cellulose depends on the viscosity level of the cellulose and is typically from 0.1 to 10% by weight, based on the solution or suspension ready for use. Examples of substituted celluloses of the present invention are carboxymethylcellulose, ethylcellulose or methylcellulose or hydroxypropylcellulose and the like. The proportion of polyvinylpyrrolidone (polyvidone type) is usually from 0.1 to 10% by weight, based on the solution or suspension ready for use. Sheet silicates such as Veegum or bentonite can be used alone or in combination with water soluble thickeners. The total proportion of thickeners is then advantageously between 0.1 and 7% by weight, based on the solution or suspension ready for use. Alginate and alginic acid are typically added at a ratio of 0.1 to 10% by weight, based on the solution or suspension ready for use. Further pharmaceutical excipients preferably use insoluble crosslinked polyvinylpyrrolidone (crospovidone) and microcrystalline cellulose. In this case, loose precipitates were formed, which were observed to interfere with the aggregation of the individual active ingredient units. The proportion of crospovidone: individual active ingredient units is advantageously 1: 1 to 0.5: 1 (by weight). Microcrystalline cellulose conventionally used in a proportion of 0.5 to 5% by weight, based on the solution or suspension ready for use, is suitable for this purpose. The proportion of the individual active ingredients in the solution or suspension ready for use is from 1 to 20% by weight, preferably from 1 to 15% by weight and very preferably from 5 to 10%, based on the solution or suspension ready to be used. to be. Preference is given to using water as a solvent or dispersant for solutions or suspensions.
[355] Examples of other suitable excipients that may be present in the solutions or suspensions of the present invention include, for example, flavoring substances (eg, flavoring and sweetening agents), buffering agents, preservatives, or other emulsifiers. Perfume is usually added at a ratio of 0.05 to 1% by weight. Examples of other flavoring agents include acids such as citric acid, sweeteners such as saccharin, aspartame, sodium cyclamate or maltol, and these are added according to certain results. Examples of emulsifiers are lecithin, sodium lauryl sulfate, Tweens® or Span, which are usually added at a ratio of 0.01 to 1% by weight. Preference is given to adding preservatives such as benzoic acid, salts of benzoic acid, methyl 4-hydroxybenzoate, propyl 4-hydroxybenzoate, sorbic acid or salts thereof. Its ratio is determined by the preservative used, and is usually from 0.1 to 4% by weight, based on the solution or suspension ready for use.
[356] The solution or suspension of the present invention is produced by techniques known to those skilled in the art. If it is desired to produce a powder for reconstitution, it is preferred to produce a mixture of the individual active ingredient units with a thickener and, as appropriate, further excipients. The powdered mixture for reconstitution is then mixed with an appropriate amount of water just prior to administration. Solutions or suspensions ready for use may be produced by adding individual active ingredient units to a dispersion of thickeners and suitably additives in water, or by adding thickeners to a dispersion of individual active ingredient units in water.
[357] In a preferred embodiment, the present invention relates to a rapid disintegrating tablet or solution or suspension comprising a PDE inhibitor as an active ingredient and a formulation of the present invention. In this case, the PDE inhibitors are preferably roflumilast and fumapentrin.
[358] Dosage formulations of the invention can be used for the treatment and prevention of any disease considered to be treatable or preventable by the use of certain active ingredients. Such dosage forms comprise certain active ingredients in conventional formulations for the treatment of certain diseases.
[359] The production of dosage forms and formulations of the invention will be illustrated by the following examples. The following examples are intended to illustrate the invention in detail, not to limit it.
[360] Preparation of Formulations (Active Component Units)
[361] Example 1
[362] 50 g of solid paraffin, 34.9 g of cetyl alcohol and 0.1 g of stearylamine are converted to a clear melt. 5.0 g of povidone is dissolved in a clear melt. 10.0 g of pantoprazole sodium sesquihydrate was added at a temperature of 56 ° C. to 60 ° C. and it was suspended uniformly. The suspension was ruffled in the molten state and the resulting droplets solidified in the cooling zone.
[363] Example 2
[364] 55 g of solid paraffin, 30.9 g of cetyl alcohol and 0.1 g of stearylamine were converted to a clear melt. 4.0 g of povidone was dissolved in a clear melt. At a temperature of 56 ° C. to 60 ° C., 10.0 g of pantoprazole magnesium was added and it was suspended homogeneously. The suspension was ruffled in the molten state and the resulting droplets solidified in the cooling zone.
[365] Example 3
[366] 45.0 g of solid paraffin, 33.8 g of cetyl alcohol, 1.0 g of β-sitosterol and 0.2 g of stearylamine were converted to a clear melt. 1.0 g of povidone and 4.0 g of ethylcellulose were dissolved in a clear melt. At a temperature of 56 ° C. to 60 ° C., 15.0 g of pantoprazole sodium sesquihydrate was added and it was suspended homogeneously. The suspension was ruffled in the molten state and the resulting droplets solidified in the cooling zone.
[367] Example 4
[368] 52.0 g of solid paraffin, 30.3 g of cetyl alcohol and 0.2 g of stearylamine were converted to a clear melt. 5.0 g of povidone was dissolved in the clear melt. At a temperature of 56 ° C. to 60 ° C., 12.5 g of pantoprazole sodium sesquihydrate was added and it was suspended homogeneously. The suspension was ruffled in the molten state and the resulting droplets solidified in the cooling zone.
[369] Example 5
[370] 77.2 g of cetyl alcohol and 0.3 g of stearylamine were converted to a clear melt. 10.0 g of povidone was dissolved in a clear melt. 12.5 g of pantoprazole sodium sesquihydrate was added at a temperature of 56 ° C. to 60 ° C. and it was suspended homogeneously. The suspension was ruffled in the molten state and the resulting droplets solidified in the cooling zone.
[371] Example 6
[372] 47 g of solid paraffin, 40 g of glyceryltripalmitate (Dynasan 116, available from Huls) and 3 g of cytosterol were converted to a clear melt at 100 ° C. and cooled to 55 ° C. to 60 ° C. 10 g of lansoprazole was added and it was suspended homogeneously. The suspension was placed in a feed container of a prill handling unit (brass commercially available) and ruffled from a 200 μm nozzle at about 0.1 bar. At this time, a periodic vibration of about 390 Hz was transmitted to the nozzle head. The resulting droplets were solidified in the cooling zone using air at a temperature of -30 ° C.
[373] Example 7
[374] 15 g of glyceryl trimyristate (Dynasan 114), 15 g of glyceryl tripalmitate (Dynasan 116), 50 g of solid paraffin and 5 g of cholesterol were converted to a clear melt at a temperature of about 100 ° C. The clear melt was cooled to about 55 ° C to 65 ° C. 15 g of rabeprazole was added, the active ingredient was dispersed uniformly and the homogeneous suspension was ruffled as in Example 6.
[375] Example 8
[376] 10 g of glyceryl tripalmitate (Dynasan 116), 20 g of glyceryl trimyristate (Dynasan 114), 52 g of solid paraffin and 3 g of cytosterol were converted to a clear melt at a temperature of about 100 ° C. The clear melt was cooled to 55-65 ° C. 15 g of omeprazole Mg was added and it was suspended homogeneously. The suspension was placed in a feed container of a prill handling unit (brass commercially available) and ruffled from a 200 μm nozzle at 90 mbar. At this time, a periodic vibration of about 400 Hz was transmitted to the nozzle head. The resulting droplets were solidified with air in the cooling zone at a temperature of -30 ° C.
[377] Example 9
[378] 18 g of tristearin, 60 g of solid paraffin and 5 g of cholesterol were converted to a clear melt. The clear melt was cooled to 56-60 ° C. 10 g of pantoprazole sodium sesquihydrate was added and homogeneously dispersed. The suspension was ruffled using a vibrating nozzle in a ruffle treatment unit (brass commercially available) in the molten state and the resulting droplets solidified in the cooling zone.
[379] Example 10
[380] 18 g cetyl palmitate, 40 g solid paraffin and 2 g cholesterol were converted to a clear melt. The clear melt was cooled to 56-60 ° C. 10 g of pantoprazole sodium sesquihydrate was added and homogenized until a uniform suspension was produced. The suspension was ruffled using a vibrating nozzle in a ruffle treatment unit (brass commercially available) in the molten state and the resulting droplets solidified in the cooling zone.
[381] Example 11
[382] 50 g of solid paraffin and 40 g of cetyl palmitate [Cutina® CP] were converted to a clear melt at 100 ° C. The clear melt was cooled to 50-60 ° C. 10 g of pantoprazole sodium sesquihydrate was added and suspended homogeneously. The suspension was ruffled using a vibrating nozzle (200 μm nozzle) in a ruffle treatment unit (brass commercially available) in the molten state and the resulting droplets solidified in the cooling zone.
[383] Example 12
[384] 50 g of solid paraffin and 40 g of cetyl alcohol were converted to a clear melt at 100 ° C. The clear melt was cooled to 50-60 ° C. 10 g of pantoprazole sodium sesquihydrate was added and suspended homogeneously. The suspension was ruffled using a vibrating nozzle (200 μm nozzle) in a ruffle treatment unit (brass commercially available) in the molten state and the resulting droplets solidified in the cooling zone.
[385] Example 13
[386] 50 g of solid paraffin and 40 g of glyceryl trimyristate were converted to a clear melt at 100 ° C. The clear melt was cooled to 50-60 ° C. 10 g of pantoprazole sodium sesquihydrate was added and suspended homogeneously. The suspension was ruffled using a vibrating nozzle (200 μm nozzle) in a ruffle treatment unit (brass commercially available) in the molten state and the resulting droplets solidified in the cooling zone.
[387] Example 14
[388] 47 g of solid paraffin, 40 g of glyceryl tripalmitate (Dynasan 116, available from Huls) and 3 g of cytosterol were converted to a clear melt at 100 ° C. and cooled to 55 ° C. to 60 ° C. 10 g of lansoprazole was added and it was suspended homogeneously. The suspension was placed in a feed container of a prill handling unit (brass commercially available) and ruffled from a 200 μm nozzle at about 0.1 bar. At this time, a periodic vibration of about 390 Hz was transmitted to the nozzle head. The resulting droplets were solidified in the cooling zone using air at a temperature of -30 ° C.
[389] Example 15
[390] 30 g of tristearin, 60 g of solid paraffin and 4 g of cytosterol and 0.07 g of stearylamine were converted to a clear melt. The clear melt was cooled to 56-60 ° C. 15 g of pantoprazole sodium sesquihydrate was added and dispersed homogeneously. The suspension was ruffled using a vibrating nozzle in a ruffle treatment unit (brass commercially available) in the molten state and the resulting droplets solidified in the cooling zone.
[391] Example 16
[392] 17.5 g of glyceryl trimyristate (Dynasan 114), 67.5 g of solid paraffin and 5 g of cholesterol were converted to a clear melt at a temperature of about 100 ° C. The clear melt was cooled to about 55 ° C to 65 ° C. 10 g of pantoprazole was added, the active ingredient was dispersed uniformly and the homogeneous suspension was ruffled as in Example 6.
[393] Example 17
[394] 98 g cetyl alcohol and 1 g solid paraffin were converted to a clear melt at about 90 ° C. 1 g of roflumilast was added and the mixture was stirred until a clear solution. The clear melt was prilled in an appropriate vibrating prill treatment unit (conditions: 200 or 350 μm nozzle, pressure 100-170 mbar, frequency about 1 Hz) at about 70 ° C.
[395] Example 18
[396] 90 g of glyceryl monostearate was converted to a clear melt at about 90 ° C. 10 g of roflumilast was added and the mixture was stirred until a clear solution. The clear melt was prilled at about 70 ° C. in a suitable vibrating prill processing unit (conditions: 200 or 350 μm nozzle, pressure 100-170 mbar, frequency about 1 Hz).
[397] Example 19
[398] 88 g of glyceryl myristate and 11.2 g of paraffin were converted to a clear melt at about 90 ° C. 0.8 g roflumilast was added and the mixture was stirred until a clear solution. The clear melt was prilled in an appropriate vibrating prill treatment unit (conditions: 200 or 350 μm nozzle, pressure 100-170 mbar, frequency about 1 Hz) at about 70 ° C.
[399] Example 20
[400] 96 g cetyl alcohol and 2 g ethylcellulose were converted to a clear melt at about 90 ° C. 2 g of roflumilast was added and the mixture was stirred until a clear solution. The clear melt was ruffled at about 70 ° C. in a suitable vibrating prill processing unit (conditions: 200 or 350 μm nozzle, pressure 100-170 mbar, frequency about 1 Hz).
[401] Example 21
[402] 84 g of glyceryl monostearate and 8 g of paraffin were converted to a clear melt at about 90 ° C. 8 g of roflumilast was added and the mixture was stirred until a clear solution. The clear melt was prilled at about 70 ° C. in a suitable vibrating prill processing unit (conditions: 200 or 350 μm nozzle, pressure 100-170 mbar, frequency about 1 Hz).
[403] Example 22
[404] 59 g of glyceryl monostearate, 20 g of cetyl palmitate and 20 g of paraffin were converted to a clear melt at about 90 ° C. 1 g of roflumilast was added and the mixture was stirred until a clear solution. The clear melt was prilled at about 70 ° C. in a suitable vibrating prill processing unit (conditions: 200 or 350 μm nozzle, pressure 100-170 mbar, frequency about 1 Hz).
[405] Example 23
[406] 50 g cetyl alcohol, 5 g glyceryl monostearate, 10 g cetyl palmitate, 10 g glyceryl tristearate and 24.5 g paraffin were converted to a clear melt at about 90 ° C. 0.5 g of roflumilast was added and the mixture was stirred until a clear solution. The clear melt was prilled at about 70 ° C. in a suitable vibrating prill processing unit (conditions: 200 or 350 μm nozzle, pressure 100-170 mbar, frequency about 1 Hz).
[407] Example 24
[408] 70 g of cetyl alcohol and 29.5 g of paraffin were converted to a clear melt at about 90 ° C. 0.5 g of roflumilast was added and the mixture was stirred until a clear solution. The clear melt was prilled in an appropriate vibrating prill treatment unit (conditions: 200 or 350 μm nozzle, pressure 100-170 mbar, frequency about 1 Hz) at about 75 ° C. to 80 ° C.
[409] Example 25
[410] 97.7 g of cetyl alcohol and 0.3 g of ethylcellulose were converted to a clear melt at about 90 ° C. 2 g of fumafenthrin was added and the mixture was stirred until a clear solution. The clear melt was prilled in an appropriate vibrating prill treatment unit (conditions: 200 or 350 μm nozzle, pressure 100-170 mbar, frequency about 1 Hz) at about 75 ° C. to 80 ° C.
[411] Example 26
[412] 69 g cetyl alcohol, 5 g cetyl palmitate, 10 g glyceryl tristearate and 15 g paraffin were converted to a clear melt at about 90 ° C. 1 g of fumafenthrin was added and the mixture was stirred until a clear solution. The clear melt was prilled at about 70 ° C. in a suitable vibrating prill processing unit (conditions: 200 or 350 μm nozzle, pressure 100-170 mbar, frequency about 1 Hz).
[413] Example 27
[414] 40 g cetyl alcohol, 7 g cetyl palmitate, 33 g glyceryl tristearate and 15 g paraffin were converted to a clear melt at about 90 ° C. 5 g of (7R, 8R, 9R) -2,3-dimethyl-8-hydroxy-7- (2-methoxyethoxy) -9-phenyl-7,8,9,10-tetrahydroimidazo [ 1,2-h] [1,7] naphthyridine was added and the mixture was stirred until a clear solution. The clear melt was prilled at about 70 ° C. in a suitable vibrating prill processing unit (conditions: 200 or 350 μm nozzle, pressure 100-170 mbar, frequency about 1 Hz).
[415] Example 28
[416] 41 g cetyl alcohol, 7 g cetyl palmitate, 33 g glyceryl tristearate and 17 g paraffin were converted to a clear melt at about 90 ° C. 2 g of (7R, 8R, 9R) -2,3-dimethyl-8-hydroxy-7- (2-methoxyethoxy) -9-phenyl-7,8,9,10-tetrahydroimidazo [ 1,2-h] [1,7] naphthyridine was added and the mixture was stirred until a clear solution. The clear melt was prilled at about 70 ° C. in a suitable vibrating prill processing unit (conditions: 200 or 350 μm nozzle, pressure 100-170 mbar, frequency about 1 Hz).
[417] Example 29
[418] 41 g cetyl alcohol, 7 g cetyl palmitate, 33 g glyceryl tristearate and 17 g paraffin were converted to a clear melt at about 90 ° C. 2 g of (7R, 8R, 9R) -2,3-dimethyl-8-hydroxy-7- (2-methoxyethoxy) -9-phenyl-7,8,9,10-tetrahydroimidazo [ 1,2-h] [1,7] naphthyridine was added and the mixture was stirred until a clear solution. The clear melt was prilled at about 70 ° C. in a suitable vibrating prill processing unit (conditions: 200 or 350 μm nozzle, pressure 100-170 mbar, frequency about 1 Hz).
[419] Example 30
[420] 38 g of glyceryl tripalmitate, 2 g of cholesterol and 59.5 g of paraffin were converted to a clear melt at about 100 ° C. 0.5 g of ciclesonide was then added and the melt was ruffled at about 75 ° C. in an appropriate vibratory prill handling unit (condition: 100 μm nozzle, pressure 100-170 mbar, frequency about 1.3 Hz).
[421] Example 31
[422] 38 g of glyceryl tripalmitate, 10 g of cetyl alcohol, 2 g of cholesterol and 49.5 g of paraffin were converted to a clear melt at about 100 ° C. 0.5 g of ciclesonide was then added and the melt was ruffled at about 75 ° C. in an appropriate vibratory prill handling unit (condition: 100 μm nozzle, pressure 100-170 mbar, frequency about 1.3 Hz).
[423] Example 32
[424] 36 g cetyl alcohol, 60 g glyceryl monostearate and 2 g vinylpyrrolidone / vinyl acetate copolymer and 2 g fumafenthrin were converted to a clear melt. The clear melt was ruffled using a nozzle at about 60 ° C. and the resulting droplets solidified by cooling.
[425] Example 33
[426] 30 g glyceryl trimyristate, 45 g glyceryl monostearate and 20 g cetyl alcohol were converted to a clear melt. 5 g of roflumilast was added and dispersed homogeneously. The melt was ruffled at about 65 ° C. and the resulting droplets solidified in the cooling zone.
[427] Example 34
[428] 80 g cetostearyl alcohol, 0.5 g sodium stearate, 5 g vinylpyrrolidone / vinyl acetate copolymer and 12.5 g glycerol trimyristate were converted to a clear melt at about 70 ° C. 2 g of (7R, 8R, 9R) -2,3dimethyl-8-hydroxy-7- (2-methoxyethoxy) -9-phenyl-7,8,9,10-tetrahydroimidazo [1 , 2-h] [1,7] naphthyridine was added at 60 ° C. and it was homogeneously dispersed. The mixture was ruffled at 60 ° C. and the resulting droplets solidified in the cooling zone.
[429] Example 35
[430] 20 g glyceryl trimyristate, 14.5 g glyceryl monostearate, 60 g cetyl alcohol and 5 g vinylpyrrolidone / vinyl acetate copolymer were converted to a clear melt at about 70 ° C. 0.5 g of ciclesonide was added and dispersed homogeneously. The clear melt was ruffled and the resulting droplets solidified in the cooling zone.
[431] Example 36
[432] 56.7 g cetyl alcohol, 3 g vinylpyrrolidone / vinyl acetate copolymer, 15 g solid paraffin, 15 g cetyl palmitate and 0.1 g sodium stearate were converted to a clear melt. 10.0 g of pantoprazole sodium sesquihydrate was added at a temperature of 56 ° C. to 60 ° C. and it was suspended homogeneously. The suspension was ruffled at 60 ° C. in the molten state, and the resulting droplets solidified in the cooling zone.
[433] Example 37
[434] 46.7 g cetostearyl alcohol, 4 g vinylpyrrolidone / vinyl acetate copolymer, 23 g solid paraffin, 0.3 g sodium stearate and 1 g cytososterol were converted to a clear melt. 10.0 g of pantoprazole sodium sesquihydrate was added at a temperature between 60 ° C. and 65 ° C. and it was suspended homogeneously. The suspension was ruffled at 60 ° C. to 65 ° C. in the molten state, and the resulting droplets were solidified in the cooling zone.
[435] Example 38
[436] 39.9 g cetyl alcohol, 3 g vinylpyrrolidone / vinyl acetate copolymer, 20 g cetyl palmitate, 2 g cholesterol, 17 g solid paraffin and 0.1 g sodium stearate were converted to a clear melt. At a temperature of 56 ° C. to 60 ° C., 18.0 g of pantoprazole sodium sesquihydrate was added and it was suspended homogeneously. The suspension was ruffled at 60 ° C. in the molten state, and the resulting droplets solidified in the cooling zone.
[437] Example 39
[438] 47.9 g cetostearyl alcohol, 2 g vinylpyrrolidone / vinyl acetate copolymer, 25 g cetyl palmitate, 1 g cytosterol, 15 g solid paraffin and 0.1 g sodium stearate were converted to a clear melt. At a temperature of 56 ° C. to 60 ° C., 15.0 g of pantoprazole sodium sesquihydrate was added and it was suspended homogeneously. The suspension was ruffled at 60 ° C. in the molten state, and the resulting droplets solidified in the cooling zone.
[439] The formulations obtained in the same manner as in Examples 1 to 39 had particle sizes of 50 to 700 µm. The processing conditions can be changed to obtain larger particles.
[440] Generation of Dosage Forms
[441] Example A
[442] 134.7 g of mannitol, 30 g of Kollidon® 30 and 20 g of xanthan were dry mixed. The mixture was granulated in a fluid bed granulator in water. Granules with a particle size of 0.8-1.5 mm were obtained and mixed with the preparation (125 g) obtained as in Example 1. The mixture thus obtained is filled into bags (vesicles) or, if necessary, compressed into tablets by methods known to those skilled in the art together with additional tablet excipients.
[443] Example B
[444] The content corresponding to 22.6 mg of pantoprazole magnesium of the formulation obtained as in Example 2 was mixed with 500 mg of lactose and 100 mg of xanthan. Thereafter, the mixture was mixed with the flavoring substance (sweetener, flavoring) according to the individual tastes, and then it was filled into bags (vesicles). The suspension for oral ingestion is obtained by dissolving the contents of the bag in a glass of water with stirring.
[445] Example C
[446] The content corresponding to 45.2 mg of pantoprazole sodium sesquihydrate of the formulation obtained as in Example 3 was mixed with an appropriate amount of lactose. The mixture was then mixed with citric acid and sodium carbonate mixture. Appropriate glidants (eg, sodium stearyl fumarate) were added and one or more suitable flavoring materials were added and then the resulting mixture was compressed directly (without further granulation process) into a foamable tablet. Oral suspensions are obtained by dissolving the tablets in 1 glass of water.
[447] Example D
[448] The content corresponding to 45.2 mg of pantoprazole sodium sesquihydrate of the formulation obtained as in Example 4 is mixed with an appropriate amount of lactose to improve the flow characteristics. The mixture is then filled into hard gelatin capsules of suitable size with appropriate other active ingredients (eg, amoxicillin or NSAIDs in conventional dosage forms).
[449] Example E
[450] 300 mg of lactose was added to a content corresponding to 30 mg of lansoprazole of the formulation obtained as in Example 6. The two components were mixed with citric acid and sodium carbonate, the addition of the appropriate glidants (eg sodium stearyl fumarate) and the appropriate flavoring material, followed by compression into tablets.
[451] Example F
[452] 450 mg of sucrose and 300 mg of xanthan were added to an amount corresponding to 30 mg of rabeprazole of the formulation obtained as in Example 7. The ingredients were mixed and a flavor mask added. The granules were filled into vesicles. The filling of the vesicles is poured into a glass of water, which is stirred and ready for use.
[453] Example G
[454] The 60 g formulation of Example 8 was dry mixed with 140 g mannitol, 30 g Kollidon 30 and 20 g xanthan. The mixture was granulated in a fluid bed granulator with water. Granules having a particle size of 0.8 to 1.5 mm were obtained. The mixture obtained in this manner was filled into a bag (vesicle).
[455] Example H
[456] 140 g of mannitol, 30 g of Kollidon 30 and 20 g of xanthan were dry mixed and granulated in a fluid bed granulator with water. The resulting granules were sieved. A screen fraction of 0.8-1.5 mm was mixed with 6.98 g of the formulation from Example 18 and filled into bags (vesicles).
[457] Example I
[458] 5 g of the formulation of Example 17 was mixed with 50 g of lactose and 8 g of xanthan. Sweeteners and flavorings were added to this mixture and filled into bags (vesicles). The bag was stirred with 1 glass of water to obtain a suspension ready for drinking.
[459] Example J
[460] 12.5 mg of the formulation from Example 19 was mixed with the appropriate amount of lactose. This mixture was mixed with a mixture of sodium carbonate and citric acid. Appropriate glidants (eg, sodium stearyl fumarate) were added, and after the addition of the flavoring and sweetening agents, the mixture obtained in this way was directly compressed into a foamable tablet. The tablets are poured into a glass of water and dissolved to obtain a suspension ready for drinking.
[461] Example K
[462] 100 mg of the formulation from Example 20 was mixed with 1.9 g of lactose and filled into 10 hard gelatin capsules.
[463] Example L
[464] 500 mg of the formulation of Example 21 was granulated with water, 15 g mannitol and 4 g Kollidon. Sufficient granules for 100 single doses were packaged in capsules.
[465] Example M
[466] 1 g of the formulation of Example 26 was mixed with 0.2 g of xanthan, 0.1 g of saccharin sodium, 1.5 g of mannitol and 0.3 g of dry orange flavoring, which was filled into a vesicle. It was stirred in about 100 mL of water to obtain a suspension ready for use.
[467] Example N
[468] 200 mg of the formulation of Example 27 was mixed with 670 mg of Destab95 SE, 2270 mg of Pearlitol 300 DC and 50 mg of crospovidone in a free fall mixer. Thereafter, 10 mg of magnesium stearate was sieved. This mixture was compressed with a tablet press.
[469] Example O
[470] The 40 mg formulation of Example 30 was mixed with 500 mg MagGran CC, 200 mg Karion and 70 mg crospovidone in a free fall mixer. Thereafter, 12 mg of magnesium stearate was added through a sieve, and it was stirred briefly again. The mixture obtained in this way was compressed with a tablet press.
[471] Example P
[472] ① Formulation of Example 22 12.500 mg
[473] ② Lactose-1-hydrate 172.125 mg
[474] ③ 45.000 mg of corn starch
[475] ④ Polyvidon® 25 12.500 mg
[476] ⑤ Insoluble Polyvidon 12.500 mg
[477] ⑥ fragrance 2.500 mg
[478] ⑦ Aspartame 0.375 mg
[479] ⑧ Citric acid 2.500 mg
[480] ⑨ Magnesium Stearate 2.500 mg
[481] Total 262.500 mg
[482] Preparation : Granulate ② and ③ with the solution of ④. The granules are dried and sieved. After mixing ⑤ using the free-fall mixer, mix ⑥, ⑦, and ⑧. ① was mixed and finally, ⑨ was mixed lightly with a free-fall mixer. The mixture thus obtained was compressed with a tablet press.
[483] Example Q
[484] ① 25.000 mg of the formulation of Example 23
[485] ② Cellactose (registered trademark) 229.625 mg
[486] ③ sodium carboxymethyl starch 12.500 mg
[487] ④ 2.500 mg of fragrance
[488] ⑤ Aspartame 0.375 mg
[489] ⑥ 2.500 mg citric acid
[490] ⑦ Magnesium Stearate 2.500 mg
[491] Total 275.000 mg
[492] Recipe : Mix ② and ③. Mix ④, ⑤, and ⑥. ① was mixed and finally, ⑨ was mixed lightly with a free-fall mixer. The mixture thus obtained was compressed with a tablet press.
[493] Example R
[494] ① 12.500 mg of the formulation of Example 22
[495] ② lactose-1-hydrate 49.660 mg
[496] ③ corn starch 13.390 mg
[497] ④ Polyvidon® K 90 1.300 mg
[498] ⑤ mannit 32.240 mg
[499] ⑥ 12.890 mg of insoluble PVP
[500] ⑦ fragrance 0.330 mg
[501] ⑧ Magnesium Stearate 1.650 mg
[502] Total 123.960 mg
[503] Preparation : granulate ② and ③ into a solution of ④. The granules are dried and sieved. ①, ⑤, ⑥, and ⑦ were mixed with the free fall mixer, and then ⑧ was mixed with the free fall mixer for a while. The mixture thus obtained was compressed with a tablet press.
[504] Example S
[505] ① 12.500 mg of the formulation of Example 22
[506] ② Lactose-1-hydrate 70.300 mg
[507] ③ potato starch 19.480 mg
[508] ④ corn starch 2.370 mg
[509] ⑤ sodium carboxymethyl starch 1.900 mg
[510] ⑥ 0.330 mg of fragrances
[511] ⑦ Magnesium Stearate 0.950 mg
[512] Total 105.930 mg
[513] Preparation : granulate ② and ③ into a solution of ④. The granules are dried and sieved. ①, ⑤, and ⑥ were mixed with the free fall mixer, and then ⑦ was mixed briefly with the free fall mixer. The mixture thus obtained was compressed with a tablet press.

权利要求:
Claims (10)
[1" claim-type="Currently amended] A formulation wherein the active ingredient is substantially uniformly dispersed in an excipient matrix consisting of one or more excipients selected from the group of fatty alcohols, triglycerides, partial glycerides and fatty acid esters.
[2" claim-type="Currently amended] Wherein the active ingredient is substantially uniformly dispersed in an excipient matrix consisting of one or more solid paraffins with one or more excipients selected from the group of fatty alcohols, triglycerides, partial glycerides and fatty acid esters.
[3" claim-type="Currently amended] The active ingredient is present in a matrix consisting of i) at least one fatty alcohol and at least one solid paraffin, or ii) in a matrix consisting of at least one triglyceride and at least one solid paraffin, or iii) at least one. An agent present in a matrix consisting of a partial glyceride and at least one solid paraffin, or iv) present in a matrix consisting of at least one fatty acid ester and at least one solid paraffin.
[4" claim-type="Currently amended] The formulation of claim 1, wherein the formulation is in the form of microspheres.
[5" claim-type="Currently amended] The formulation according to claim 4, which can be obtained by prilling a solution or dispersion of the active ingredient in a melt of excipient using a vibrating nozzle.
[6" claim-type="Currently amended] The formulation of claim 1, wherein the active ingredient is selected from the group of PDE inhibitors, reversible proton pump inhibitors and glucocorticosteroids.
[7" claim-type="Currently amended] The formulation of claim 1, wherein at least one other excipient selected from the group of polymers and sterols is present in the formulation.
[8" claim-type="Currently amended] A pharmaceutical dosage form comprising a formulation according to claim 1 together with at least one pharmaceutical excipient.
[9" claim-type="Currently amended] 8. The pharmaceutical dosage form according to claim 7, wherein the excipient is in the form of a rapid disintegrating tablet, which is an excipient which causes rapid disintegration of the tablet.
[10" claim-type="Currently amended] 10. The tablet according to claim 9, wherein there is further at least one excipient selected from the group of lubricants, perfumes, flavoring substances and surfactant ingredients.

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EP1341527B1|2011-08-10|

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引用文献:

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公开号 | 申请日 | 公开日 | 申请人 | 专利标题

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法律状态:
2000-12-07|Priority to EP00126847

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2000-12-07|Priority to EP00126847.3

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2001-12-06|Application filed by 알타나 파마 아게

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2001-12-06|Priority to PCT/EP2001/014307

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2003-09-15|Publication of KR20030072557A

优先权:

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申请号 | 申请日 | 专利标题

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EP00126847|2000-12-07|

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EP00126847.3|2000-12-07|

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PCT/EP2001/014307|WO2002045693A1|2000-12-07|2001-12-06|Pharmaceutical preparation comprising an active dispersed on a matrix|