• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    The invention provides a stable and solid formulation of a proton pump inhibitor plus vitamins (cyanocobalamin and vitamin C) by applying to the enterically covered pellets, which in turn have been covered with a film to prevent them from taking them together absorption decrease by taking together causing serious damage to health. The pharmaceutical composition of this invention comprises: a proton pump inhibitor, vitamin B12, vitamin C and as excipients: hydroxypropyl methylcellulose, magnesium stearate. The enteric shell will be formed for example of a copolymer of methacrylic acid, mono and diglycerides, triethylcitrate and polysorbate 80. (Machine-translation by Google Translate, not legally binding)
    公开号:ES2723873A1
    申请号:ES201700393
    申请日:2018-03-01
    公开日:2019-09-03
    发明作者:Hernan Ma Carmen Batanero；Jimenez Emilio Garcia；Chamorro Miguel Rodriguez；Carrasco Hebbe Isabel Campero
    申请人:Hernan Ma Carmen Batanero；Jimenez Emilio Garcia；Chamorro Miguel Rodriguez；Carrasco Hebbe Isabel Campero；
    IPC主号:
    专利说明:

    [0001] Medication formulated with omeprazole and vitamin B 12 .
    [0002] Technical sector
    [0003] Pharmaceutical sector.
    [0004] The present invention relates to a solid oral galenic formulation comprising the combination of proton pump inhibitor and cyanocobalamin.
    [0005] State of the art
    [0006] With this invention it is a matter of galenically formulating a medicament that treats gastric hyperacidity while decreasing the probability of producing vitamin deficiency. By this method a therapeutically effective amount of one or more substances that reduce gastric acid together with an effective supplementary amount of one or more vitamins such as B 12 and C would be administered. Layers that delay absorption of the pump inhibitor from the pump will be applied. protons to allow time for the absorption of vitamins in acidic medium, since if this inhibitor acts before, the environment is basified and they are not effective.
    [0007] The present invention includes methods for preparing oral dosage forms, which may involve the application of a free vitamin B 12 coating to a suitable pharmaceutical preparation consisting of one or more substances that neutralize or reduce gastric acid. Detailed description of the invention
    [0008] The galenic formulation of the claimed invention consists of a proton pump inhibitor plus vitamins. To alleviate the deficit caused by the former, by decreasing the acidity of the stomach necessary for vitamins to exert their therapeutic function, it will proceed, and here lies its originality, applying layers that delay the absorption of the proton pump inhibitor to allow time to the absorption of vitamins in acidic medium, since if this inhibitor acts before, the environment is basified (they increase gastric pH) and are not effective, causing diseases.
    [0009] Proton pump inhibitors include 2-pyridylmethylsulfinylbenzimidazole compounds that differ in substituent groups: Ianzoprazole, omeprazole, rabeprazole and pantoprazole. The therapeutically effective amounts of these vary from about 10 milligrams to about 40 milligrams.
    [0010] Vitamins include: ascorbic acid (20 milligrams to approximately 2 grams) and cyanocobalamin (0.5 micrograms, or 25% of the adult's estimated average requirement (EAR), at approximately 5 milligrams).
    [0011] The term "gastric hyperacidity" refers in this document to the symptoms characterized by an excess of hydrochloric acid in the stomach, which includes, hyperchlorhydria, gastroesophageal reflux disease, gastric or gastroduodenal ulcers, gastritis, hiatus hernia and related tract ailments gastrointestinal.
    [0012] Gastric hyperacidity is treated with pharmaceutical preparations comprising one or more pharmacologically active substances that neutralize or reduce gastric acid. Pharmacologically active substances that neutralize gastric acid are commonly known as "antacids." The most prescribed pharmacologically active substances To reduce gastric acid hypersecretion they are generally classified as "proton pump inhibitors" and "histamine H 2 receptor antagonists".
    [0013] The term "proton pump inhibitor" as used herein refers to a pharmacologically active substance that irreversibly binds to the H / K ATPase, an enzyme that is located on the secretory surface of the parietal cells of the stomach. This enzyme is essential for the final transport of hydrogen ions in the stomach by catalyzing the exchange of protons (H) by potassium ions (K). This enzyme is part of the "proton pump." Inhibition of the proton pump decreases the secretion of hydrochloric acid in the stomach and alters the gastric pH.
    [0014] The proton pump inhibitors used in the dosage forms known in the art may be in neutral form or in the form of one or more alkaline salts, such as magnesium, calcium, sodium, potassium or lithium salts.
    [0015] The term "free vitamin B 12 " as used herein refers to vitamin B 12 not bound to protein. Cyanocobalamin is the free vitamin B 12 most commonly incorporated in vitamin and nutritional supplements, although it can also be used: hydroxycobalamin, methylcobalamin, aquocobalamin, acetatecobalamin, nitrocobalamin and sufitocobalamin.
    [0016] The term "coating", as used herein, refers to a material comprising one or more substances, said material results from a process of applying one or more substances to a substrate. There are four main techniques for applying coatings to pharmaceutical dosage forms: sugar coating, film coating, microencapsulation and compression coating.
    [0017] Examples of acceptable pharmaceutical preparations comprising one or more proton pump inhibitors include, without limitation, enteric coated granules. Be aware of the potentially harmful effect of vitamin B 12 malabsorption when mixed with gastric acid suppressant drugs, so periodic tests of the level of vitamin B 12 are performed and treat patients with signs of vitamin B 12 deficiency or with low levels of vitamin B 12 in the blood.
    [0018] Proton pump inhibitors reduce gastric ascorbic acid levels. (Mowat et al., Best Pract. Res. Clin. Gastroenterol. 15: 523537, 2001).
    [0019] The following examples are more illustrative of the present invention, but it is understood that the invention is not limited thereto.
    [0020] EXAMPLE 1
    [0021] This example exposes a formulation with granules of 1% cyanocobalamin and lansoprazole. A pellet comprising the lansoprazole and cyanocobalamin proton pump inhibitor can be prepared with enteric coated stratified granules, said lansoprazole granules comprising and prepared accordingly. Lansoprazole can be sprayed on seeds of sugar spheres in a fluid bed apparatus, from an aqueous suspension containing dissolved hydroxypropyl methylcellulose and sodium lauryl sulfate. The core material thus prepared can then be covered with a separation layer made with a solution of hydroxypropyl cellulose containing talc and magnesium stearate. The core material thus prepared with a separation layer can then be covered with an enteric coating consisting of copolymer of methacrylic acid, mono and diglycerides, triethyl citrate and polysorbate 80 sprayed in an inert bed apparatus. The stratified granules of Enteric coating prepared in this way will contain approximately 21% lansoprazole.
    [0022] These enteric coated stratified granules can be dry mixed with microcrystalline cellulose, crosslinked polyvinyl pyrrolidone, sodium stearyl fumarate and a 1% cyanocobalamin material in the following proportions:
    [0023] - Enteric coated granules in layers, 47 g;
    [0024] - Microcrystalline cellulose, 280 g
    [0025] - Cross-linked polyvinylpyrrolidone, 5 g
    [0026] - Sodium stearyl fumarate, 0.5 g
    [0027] - 1% cyanocobalamin material, 27.5 g.
    [0028] 1% Cyanocobalamin is a pink powder free of almost spherical particles or agglomerates and consists of USP cyanocobalamin in a matrix of citric acid buffered maltodextrin and trisodium citrate.
    [0029] EXAMPLE 2
    [0030] In this example there is 1% cyanocobalamin and ascorbic acid mixed together with lansoprazole, as a proton pump inhibitor and ascorbic acid and cyanocobalamin can be added in a layered covering covering the pellets above the preparation and which could contain approximately 21% lansoprazole.
    [0031] The enteric layer coating on the pellets can be dry mixed with microcrystalline cellulose, cross-linked polyvinylpyrrolidone, 1% cyanocobalamin, 97% ascorbic acid, for direct compression and magnesium stearate in the following proportions:
    [0032] - Enteric layered cover on the pellets 47 g -1% cyanocobalamin, 27.5 g
    [0033] - 97% ascorbic acid for direct compression 283.5 g
    [0034] - Microcrystalline cellulose 237 g
    [0035] - Crosslinked polyvinylpyrrolidone 12 g
    [0036] - Magnesium stearate 3 g.
    [0037] 97% ascorbic acid for direct compression is a fine white granular powder formed by 97% USP ascorbic acid and 3% starch.
    [0038] EXAMPLE 3
    [0039] This example illustrates a formulation made with 1% cyanocobalamin and sodium ascorbate for direct compression and proton pump inhibitor pellets. In this example the inhibitor is lansoprazole and the vitamins ascorbic acid and cyanocobalamin in layers coated pellets with enteric film. The enteric film that covers the pellets will contain approximately 21% lansoprazole.
    [0040] The enteric coating covering the pellets can be dry mixed with microcrystalline cellulose, cross-linked polyvinylpyrrolidone, 1% cyanocobalamin, 99% sodium ascorbate for direct compression and magnesium stearate in the following proportion:
    [0041] -Enteric cover to cover the pellets 47 g
    [0042] - 1% cyanocobalamin, 27.5 g
    [0043] - 99% sodium ascorbate for direct compression, 157.5 g
    [0044] - 97% ascorbic acid for direct compression, 142 g.
    [0045] - 221 g microcrystalline cellulose
    [0046] - Crosslinked polyvinylpyrrolidone 12 g.
    [0047] - Magnesium stearate 3 g.
    [0048] It puts 99% sodium ascorbate for direct compression, it is a fine, granular, white or yellow powder, formed by 99% USP sodium ascorbate and 1% base starch.
    [0049] EXAMPLE 4
    [0050] Omeprazole granules can be used in tablets. The resulting granules can be formulated with an enteric coating. The sealant layer can be modified, incorporating pure vit B 12 . The seal of said layer can be applied to said enteric coated tablets as follows
    [0051] - Enteric cover, 146 g
    [0052] - Pink Opadry II, 4.5 g
    [0053] - USP cyanocobalamin, 0.22 g
    [0054] - Water 450g
    [0055] EXAMPLE 5
    [0056] The illustrated example of a capsule made of enteric shell in layers of pellets with compressed cyanocobalamin shell. A capsule comprising omeprazole, cyanocobalamin and magnesium, can be coated with enteric film. Magnesium and omeprazole can be sprayed onto sugar spheres in a fluidized bed apparatus of a water suspension containing dissolved hydroxypropyl methylcellulose. The prepared base material can be coated with a separation layer with hydroxy propylcellulose solution containing talc and magnesium stearate. It can also carry an enteric shell consisting of a copolymer of methacrylic acid, mono and diglycerides, triethylcitrate and polysorbate 80 sprayed in a fluidized bed apparatus. The enteric cover will be prepared in layers on the pellet. It will contain approximately 14% omeprazole.
    [0057] The layered cover on the pellet can be supplied with an excess layer composed of cyanocobalamin in the following way:
    [0058] - Enteric cover covering pellets, 20 kg
    [0059] - Hydroxypropyl methylcellulose, 238 g
    [0060] - USP cyanocobalamin, 16g
    [0061] - 7g magnesium stearate
    [0062] - Purified water, 6.56 kg
    [0063] - The enteric layered cover on the pellet can be coated with hydroxypropyl methylcellulose and with cyanocobalamin solution, containing magnesium stearate in a fluidized bed apparatus, it can also carry another cyanocobalamin cover and fill with hard gelatin capsules.
    [0064] BIBLIOGRAPHY
    [0065] 1- Andrés, Emmanuel, Federici, Laure. (2009). Role of Vitamin B12 in Anemia in Old Age. Archives of Internal Medicine. 169 (12), pp. 1167-1168.
    [0066] 2- Andrés E., Affenberger S., Zimmer J., (2006). Current hematological findings in cobalamin deficiency: a study of 201 consecutive patients with documented cobalamin deficiency. Clin Lab Haematol 28. pp.50-6.
    [0067] 3- Antony A.C. (2011). Megaloblastic anemias. In: Goldman L, Schafer AI, eds. Cecil Medicine
    [0068] 24th ed. Philadelphia, chap 167. Elsevier.
    [0069] 4- Antony A.C., Megaloblastic (2008). Anemias In: Hoffman R, Benz EJ, Shattil SS, et al., Eds. Hematology: Basic Principles and Practice. 5th ed. Philadelphia, chap 39. Elsevier Churchill Livingstone.
    [0070] 5- Bilbao Garay J. (2006). Deficiency anemias II: megaloblastic anemia and other deficiency anemias, of the National Health System. 30 (3).
    [0071] 6- Foumier M.R., Targownik L. E., William D., Leslie. (2009). Proton pump inhibitors, osteoporosis, and osteoporosis-related fractures Maturitas. 64 (1) 20. pp. 9-13.
    [0072] 7- Gwen M. C., Masclee, M., Sturkenboom, E., Kuipers, J. (2014). A Benefit-Risk
    [0073] Assessment of the Use of Proton Pump Inhibitors in the Elderly. Drugs Aging. 31. pp. 263-282, DOI 10.1007 / s40266-014-0166-4.
    [0074] 8- Kalisch L.M. et al. Aust (2011). Prescr. Cascade prescription, cascade of errors. 34. Pp.
    [0075] 162-6).
    [0076] 9- Lesbia Meertens R. Liseti Solano R. (2007). Vitamin B12, folic acid and mental function in older adults. Invest. Clin. Scielo Chile. 46.
    [0077] 10- Marcuard S., Albernaz L. Khazanie P. (1994). Omeprazole therapy causes malabsorption of cyanocobalamin (vitamin b 12). Ann Intem Med. 120. pp. 211-215.
    [0078] 11- O'Connell, M.B., Madden, D.M ,. Murray A.M., Heaney R.P., Kerzner, L.J. (2005). Effects of proton pump inhibitors on calcium carbonate absorption in women: a randomized crossover trial. Am. J. 118 (7). pp. 778-81.
    权利要求:
    Claims (5)
    [1]
    1. The solid, stable pharmaceutical composition is claimed whose oral formulation comprises:
    - Proton pump inhibitor (derivatives of 2-pyridylmethylsulfinylbenzimidazole) by substitution of the groups that originate different compounds.
    - B12 vitamin.
    - Vitamin C.
    - Hydroxypropyl methylcellulose.
    - Magnesium stearate.
    - Copolymer of methacrylic acid.
    - Mono and diglycerides.
    -Triethylcitrate
    - Polysorbate 80.
    [2]
    2. Pharmaceutical composition according to claim 1 the proton pump inhibitor will be selected from the group: lansoprazole, omeprazole, pantoprazole and rabeprazole, its racemic, its enantiomers, its isomers, its derivatives and its alkaline salts or components, racemic, enantiomers, isomers and derivatives, in doses of 10 mg, 20 mg, 40 mg if it is omeprazole, 15-30 mg if it is lansoprazole and 10-20 mg if it is rabeprazole.
    [3]
    3. Pharmaceutical composition according to claim 1 Vitamin B12 will normally be used in the form of cyanocobalamin and at doses of 0.1 micrograms to 0.5 milligrams, but may also be: hydroxycobalamin, methylcobalamin, hydrated cobalamin, acetatecobalamin, nitrocobalamin or sulfitocobalamin.
    [4]
    4. Pharmaceutical composition according to claim 1 vitamin C will be ascorbic acid, in its arid or basic salt, or ascorbic palmitate, in doses of 5 mg to 2 grams.
    [5]
    5. The method of preparing the composition according to claims 1-4 will be in capsules containing the proton pump inhibitor pellets plus the cyanocobalamin granules which, in turn, have been coated with a film. It can be done by two procedures:
    - Granulate the omeprazole pellets (proton pump inhibitor) with cyanocobalamin-containing powder, sift by light less than 2X diameter pellet and dry.
    - Make a granule with cyanocobalamin diluted in excipient with a similar size in doses that can be mixed with the pellets to dose capsules.
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    同族专利:
    公开号 | 公开日
    ES2723873B1|2020-05-13|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    ES2216870T3|1999-02-23|2004-11-01|MERCK & CO., INC.|PHARMACEUTICAL COMPOSITION CONTAINING INHIBITORS OF THE PUMP OF PROTONS.|
    US20040185119A1|2003-02-26|2004-09-23|Theuer Richard C.|Method and compositions for treating gastric hyperacidity while diminishing the likelihood of producing vitamin deficiency|
    US20070065508A1|2005-09-16|2007-03-22|Regents Of The University Of Colorado|Composition Comprising Vitamin B12 and Acid Reducing Agent and Uses Thereof|
    法律状态:
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    优先权:
    申请号 | 申请日 | 专利标题
    ES201700393A|ES2723873B1|2018-03-01|2018-03-01|Combination drug with omeprazole and vitamin B12|ES201700393A| ES2723873B1|2018-03-01|2018-03-01|Combination drug with omeprazole and vitamin B12|
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