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    • 专利摘要:
    Process for the preparation of synthetic camel organ extracts, the extracts prepared by the process according to the invention and their use alone and as a constituent of pharmaceutical, cosmetic, dietary and other compositions.
    公开号:CH713107A2
    申请号:CH01466/16
    申请日:2016-11-04
    公开日:2018-05-15
    发明作者:Riemschneider Randolph
    申请人:Riemschneider Randolph；
    IPC主号:
    专利说明:

    Description [0001] Animal organ extracts are of great importance as raw materials for pharmaceuticals and cosmetics. Animal placenta extracts in particular are used to a large extent in pharmaceuticals and cosmetics due to the active substances they contain [cf. "Soap-oil-fat waxes" 112, 211-218 (1986)], where in many cases they may be supplemented by low molecular weight additives.
    The frugal camel is becoming increasingly important as livestock, due to a) climate change, which leads to an increase in the desert areas of our earth, b) by the unregulated growth of our earth's population, the nutrition of which will be questioned at some point if we continue like this as before (e.g. too expensive pig and cattle breeding). The camel family includes: camel (300-950 kg) with two humps (Asia), dromedary (300-500 kg) with one hump (Africa), llama, alpacka, guanaco, vicuna. The humps are fat reservoirs.
    Since 1947, the inventor has included the camel in his research on animal organ extracts from pork, beef, horse, and has e.g. natural camel placenta extract (I) and camel thymus extract (II) are also produced and their composition is precisely analyzed in order to meet the requirements for the development of the corresponding protein-free, synthetic extract I (I, synthetic) and II (II, synthetic). A precursor to I and II was the synthetic injection preparation CELLRYL, Japan (based on calf blood SR 71) developed by the inventor, which was already characterized by cell metabolism-activating properties: Increase in ATP production in the mitochondria, measurable using the WARBURG method Factor of 1.8.
    The object of the present invention is thus to provide a method for producing synthetic camel organ extracts, and the resulting synthetic camel organ extracts, which preferably significantly improve the biochemical activity profile of the known natural and synthetic animal organ extracts.
    This object is achieved by the present invention. The synthetic camel organ extracts produced by the process according to the invention are distinguished, inter alia, by their improved cell metabolism-activating properties and are used in many areas of everyday life, including as a component of pharmaceutical compositions (for example for stimulating wound healing), as additives for cosmetics (for example in skin creams) or as a food supplement.
    SUMMARY OF THE INVENTION To achieve the present object, (1) a method for producing synthetic camel organ extracts is provided, which comprises mixing
    a. of one or more L-amino acids and their derivatives,
    b. a peptide fraction from a camel organ extract,
    c. of one or more nucleic acid components and their derivatives,
    d. one or more vitamins and mineral salts, c. and other additives, with 30-40 vol% water at a pH between 6.0 and 7.4.
    (2) Method according to item 1, wherein the L-amino acids and their derivatives are selected from the group comprising glycine, glutamic acid, alpha-alanine, aspartic acid, hydroxyproline, proline, serine, lysine, arginine, histidine, ornithine, asparagine , Valine, tyrosine, DL-threonine, phenylalanine, leucine, threonine, tryptophan, methionine, β-alanine, isoleucine, cysteine, creatinine and hippuric acid.
    (3) Method according to item 1 or 2, wherein to maintain the peptide fraction from camel organs, b1) blood-free and washed camel organ tissue is mechanically crushed to a pulp and mixed with a suitable solvent or solvent mixture, b2) this mixture for several days stored cool, and then centrifuged, b3) in the centrifugate by changing the osmotic conditions and simultaneous heating to 55-65 ° C. peptides are cleaved from the proteins present, b4) the pH is lowered to 3.2 to 3.5 by removing air or oxygen for a sufficiently long time to remove residual proteins b5) and finally filtering sterile.
    (4) Method according to one of the items 1-3, wherein the appropriate solvent mixture is an ether and ethanol and after step b3) for removing the ether, at a pH of 7.2 to 7.5, an air mixture is passed through the centrifugate.
    (5) Method according to any one of items 1-4, wherein the peptide fraction is obtained from a camel plant extract, camel thymus extract or a camel liver extract.
    (6) Method according to one of items 1 -5, wherein the nucleic acid components and their derivatives are selected from the group comprising adenine, adenosine, cytidine, guanine, cytosine, uracil, guanosine, uridine, hypoxanthine, xanthine, cycl. AMP, adenosine monophosphate, inosine, uric acid and orotic acid.
    (7) Method according to one of items 1-6, the vitamins and mineral salts being selected from the group comprising pyridoxol-HCl, biotin, thiamine chloride, calcium pantothenate, tocopherol succinate, myo-inositol, nicotina2 mid, magnesium sulfate, magnesium aspartate, sodium dihydrogen phosphate -Monohydrate, zinc acetate, cobalt gluconate and manganese gluconate.
    (8) Method according to one of items 1-7, the further additives to be selected from the group comprising glucose, sorbitol, mannitol, citric acid, malic acid, succinic acid, benzyl alcohol, glycerol, ethanol, N-methylglucamine, glucosamine, sodium lactate and sodium succinate.
    (9) Method according to one of the items 1 -8 being for the production of the synthetic camel organ extracts
    a. 0.1-50 g / l, 2-10 g / l, or 4 g / l L-amino acids or L-amino acid derivatives,
    b. the peptide fraction resulting from 0.1-10 kg, from 1-5 kg, or from 2 kg, of camel organ tissue per liter of synthetic camel organ extract,
    c. 0.01-50 g / l, 0.1-5 g / l, or 1.0 g / l nucleic acid components and their derivatives,
    d. 0.1-1.0 g / l, 0.6-0.9 g / l, or0.7g / l vitamins and 0.1-20 g / 1.1-5 g / l, or 1.5g / l mineral salts, as well
    e. and 0-200 g / l, 5-100 g / l, 80 g / l, 60 g / l or 20 g / l other additives, with 30-40 vol% water at a pH between 6.0 and 7, 4 can be mixed. (Weight / volume and volume / volume information refer to the synthetic camel organ extract final volume).
    (10) Method according to one of items 1-9, wherein for the production of the synthetic camel organ extracts
    a. as L-amino acids or L-amino acid derivatives glycine, glutamic acid 0.3-0.4 g / l each, alpha-alanine, aspartic acid, hydroxyproline, proline, serine, lysine, arginine 0.2-0.4 g / l each, Histidine, ornithine, asparagine, valine, tyrosine, DL-threonine. Phenylalanine, leucine 0.03-0.06 g / l each, threonine, tryptophan, methionine β-alanine 0.01-0.03 g / l each, isoleucine, cysteine, creatinine, hippuric acid each <0.02 g / l , Urea 0.5-0.9 g / l,
    b. as a peptide fraction, per liter of synthetic camel organ extract, the peptide fraction resulting from 2 kg of camel organ tissue,
    c. as nucleic acid components and their derivatives, adenine, adenosine, cytidine, guanine, cytosine, uracil, guanosine, uridine, hypoxanthine, xanthine, cycl.AMP adenosine monophosphate each 0.01-0.03 g / l, inosine 0.08 g / l, Uric acid and orotic acid each 0.02-0.03 g / l,
    d. as vitamins pyridoxol-HCl 0.5-0.7 g / l, biotin 0.1 g / l, thiamine chloride, calcium pantothenate, tocopherolsuecinate each <0.002 g / l, myo-inositol nicotine cream each <0.03 g / l , and as mineral salts magnesium sulfate, magnesium aspartate and sodium dihydrogen phosphate monohydrate each <0.07 g / l, zinc acetate 0.1 g / l, cobalt and manganese gluconate each 0.005 g / l.
    e. and as further additives glucose, sorbitol and mannitol each 0.1-0.5 g / l, citric acid 1-5 g / l, malic acid 1-2 g / l, succinic acid 5-15 g / l, ethanol 10-50 ml / l, benzyl alcohol 1-4 ml / l., glycerin 0.4-1.0 g / l, N-methylglucamine <0.5g / l, glucosamine 1-2.5 g / l, sodium lactate 1-4 g / l, sodium succinate 2 -15 g / l, mixed with 30-40 vol% water at a pH between 6.0 and 7.4 (values refer to the final volume). (11) Method according to one of items 1-10, wherein a yeast cell preparation is also added.
    (12) Method according to one of the items 1-11, wherein further components are added which enhance the activity of the camel organ extracts to increase the cell metabolism activity.
    (13) Method according to one of the items 1-12, wherein the synthetic camel organ extracts are admixed with further metabolic activity-increasing components.
    (14) Method according to one of items 1-13, wherein the synthetic camel organ extracts further natural or synthetic mammalian organ extracts are admixed.
    (15) Method according to one of the items 1-14, wherein the synthetic camel organ extracts further natural or synthetic plant extracts are added.
    (16) Synthetic camel organ extracts and extract mixtures, such as those obtainable by the process according to one of items 1-15.
    (17) Pharmaceutical composition comprising synthetic camel organ extracts and extract mixtures, such as those obtainable by the process according to one of items 1 to 15, for topical, subcutaneous, intravenous or intramuscular use for the purpose of external or internal wound healing, for the treatment of arteriosclerosis or radiation damage.
    (18) Use of the synthetic camel organ extracts and extract mixtures according to one of items 1 to 15 for the manufacture of a medical composition for topical, subcutaneous, intravenous or intramuscular use for the purpose of external or internal wound healing, for the treatment of arteriosclerosis or radiation damage.
    (19) Use of the synthetic camel organ extracts and extract mixtures, such as those obtainable by the process according to one of items 1 to 15, as cosmetic additives.
    (20) Use of the synthetic camel organ extracts and extract mixtures, as are obtainable by the process according to one of items 1 to 15, as a food enhancer.
    (21) Method according to one of items 1-15, wherein the synthetic camel organ extracts are mixed with one or more camel connective tissue components.
    (22) Method according to point 21, wherein the camel connective tissue components are to be selected from the group comprising collagen types, elastins, fibronectins, creatines and hyaluronic acid.
    Detailed Description of the Invention According to a first aspect of the present invention, there is provided a method of making synthetic camel organ extracts. One or more L-amino acids and their derivatives, a peptide fraction from a camel organ extract, one or more nucleic acid components and their derivatives, one or more vitamins and mineral salts and optionally other additives, with 30-40 vol% (volume percent ) Water, preferably double distilled (bidist), dissolved or mixed at a pH between 6.0 and 7.4. The individual components are mixed with stirring and under sterile conditions.
    According to the present invention, the group of L-amino acids and L-amino acid derivatives is not further restricted. In one embodiment of the invention, suitable L-amino acids and L-amino acid derivatives are asparagine, aspartic acid, cysteine, cystine, glutamic acid, glutamine, alpha-alanine, beta-alanine, arginine, glycine, histidine, delta-hydroxylysine, hydroxyproline, leucine, isoleucine, Lysine, methionine, norleucine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, alpha-aminoadipic acid, alpha-aminobutyric acid (normal), gamma-amino-n-butyric acid, beta-amino-isobutyric acid, delta-aminolevulinic acid, carbamic acid , Citrulline, creatine, creatinine, cystathionine, cyste in acid, ergothionein (betaine of thiolhistidine), glycocyamine (guinidine acetic acid), homoserine, ornithine, taurine, dyenkolic acid (cysteine thioformacetal), guanidine salts, ornithuric acid, hippuric acid, phenacetic acid, phenacetic acid, phenacetic acid L-alanine, N-acetyl-L-arginine, N-acetylglycine, N-acetyl-L-hydroxyproline, N-acetyl-L-isoasparagine, N-acetyl-L-isoleucine, N-acetyl-L-leucine, N- Acetyl-L-lysine, N-acetyl-L-met hionin, N-acetylmuramic acid, N-acetyl-L-ornithine, N-acetyl-L-phenylalanine, N-acetyl-L-proline, O-acetyl-L-serine, N-acetyl-L-threonine, N-acetyl- L-tryptophan, N-acetyl-L-valine, L-allo-isoleucine, L-allo-threonine, N-benzoyl-L-arginine, N-benzoyl-L-histidine, N-benzoyl-L-lysine, N-benzoyl- L-methionine, N-benzoyl-L-ornithine, NBenzoyl-L-phenylalanine, N-benzoyl-L-tryptophan, N-benzoyl-L-valine, S-benzoyl-L-cysteine, O-benzoyl-L-serine, O-BenzoylL-tyrosine, L-carnosine (ß-alanyl-L-histidine), Ν, Ο-diacetyl-L-threonine and O-phospho-L-serine.
    In an alternative embodiment of the invention, the group of suitable L-amino acids and LA amino acid derivatives consists of glycine, glutamic acid, alpha-alanine, aspartic acid, hydroxyproline, proline, serine, lysine, arginine, histidine, ornithine, asparagine, valine, tyrosine, DL-threonine, phenylalanine, leucine, threonine, tryptophan, methionine, β-alanine, isoleucine, cysteine, creatinine and hippuric acid.
    [0031] According to the present invention, a peptide fraction from camel organs is obtained as follows. Blood-free and washed camel organ fabric is mechanically chopped into a slurry and mixed with one or more suitable solvents for several days, e.g. 5,10 or 15 days, stored chilled (preferably at <-10 ° C), and then separated by centrifugation (for example with an explosion-proof drum centrifuge). A suitable solvent mixture is e.g. an ether and ethanol, preferably in a ratio of 13.3: 1. By changing the osmotic conditions of the centrifugate and simultaneously heating to about 60 ° C., peptides split off from the proteins contained in the centrifugate. Subsequently, at a pH of 7.2 to 7.5, air can be passed through to remove the solvent (ether). The pH is then lowered to approximately 3.4 in order to remove residual proteins by passing through air or oxygen. Protein freedom can be determined with sulfosalicylic acid. After sterile filtration (pore size: 0.22 μm), the required peptide fraction (flow rate) is obtained.
    Under camel organ or camel organ tissue according to the present invention is to be understood any organ originating from a camel or part of an organ (organ tissue). In an alternative embodiment of the invention, the camel organ or camel organ tissue is placenta, thymus, liver, spleen, heart muscle, connective tissue or salivary gland. In a preferred embodiment of the invention, the camel organ or camel organ tissue is camel placenta, camel thymus gland, camel liver, or camel salivary gland. In a further preferred embodiment of the invention, the camel organ or camel organ tissue is camel placenta or camel thymus.
    The group of nucleic acid components and nucleic acid derivatives according to the present invention is not further limited. Examples of nucleic acid components and their derivatives are 2-aminopurine, hypoxanthine, 1-methylhypoxanthine, adenine, 2-methyladenine, 6-methylaminopurine, guanine, 1-methylguanine, 7-methylguanine, 2-methylamino-6-oxodihydropurine, 8-hydroxyuanguanine, isogranine , 2,6-diaminopurine, xanthine, 1-methylxanthine, 3-methylxanthine, 7-methylxanthine, 3,9-dimethylxanthine, uric acid, 1-methyluric acid, 9-methyluric acid, 1,9-dimethyluric acid, 3,7-dimethyluric acid, 1 , 3,7-trimethyluric acid, adenosine, 3'-amino-3'-deoxy-adenosine, 9-ß-D-ribofuranosyl-6-methylanninopurine, 2'-deoxyinosine, 2'-adenylic acid, 3'-adenylic acid, 5 ' Adenylic acid, adenosine 5'-diphosphoric acid, adenosine 5'-triphosphoric acid, deoxyadenylic acid, 2'-deoxyadenosine 5'-triphosphate, N-succinyladenylic acid, 3'-guanylic acid, guanosine-5'-diphosphoric acid, guanosine 5'- triphosphoric acid, inosine-3'-phosphoric acid, inosine-5'-phosphoric acid, inosine-5'-diphosphoric acid, xanthylic acid, xanthosine-5'-monophosphoric acid, guanosine diphosphate manno se, guanosine diphosphate fructose, guanosine diphosphate fucose, diphosphopyridine nucleotide, triphosphopyridine neuelotide, cytosine, 5-methylcytosine, 5-hydroxymethylcytosine, cytimidine, thymine, uracil, willardiine, 5-aminhydroidinac, 4.5-diaminouracilacil, 4.5 5-dihydrouridine, 2-deoxyuridine, 5-methyluridine, pseudouridine, orotidine, cytidine, 2'-deoxycytidine, 5-methylcytidine, thymidine, a-thymidine, cytidine-2'-monophosphate, cytidine-3'-monophosphate, cytidine-ö 'monophosphate, cytidine 4
    5'-diphosphate, uridine 2'-monophosphate, uridine 3'-monophosphate, orotic acid, uridine 5'-monophosphate, uridine 5'-diphosphate, 5-methylcytidine-3'-monophosphate, orotidine 5'-monophosphate , Thymidine 5'monophosphate, thymidine 5'-triphosphate, 2'-deoxycytidine 5'monophosphate, 2'-deoxycytidine 5-diphosphate, uridine diphosphate glucose, uridine diphosphate galactose, uridine diphosphate arabinose, uridine diphosphate diphosphonic acid, xylose, xylose Uridine diphosphate-N-acetylgalactosamine, cytidine diphosphate-a-glycerol, cytidine diphosphate ribitol, cycl. AMP, cycl. GMP and others
    In a special embodiment of the invention, the group of nucleic acid components and nucleic acid derivatives consists of adenine, adenosine, cytidine, guanine, cytosine, uracil, guanosine, uridine, hypoxanthine, xanthine, cycl. AMP, adenosine monophosphate, inosine, uric acid and orotic acid.
    The group of vitamins and mineral salts in relation to the present invention includes all known vitamins and mineral salts. A non-exhaustive list of vitamins and mineral salts includes pyridoxol-HCI, biotin, thiamine chloride, D-panthenol, calcium pantothenate, tocopherol succinate, myo-inositol, nicotinamide, magnesium sulfate, magnesium aspartate, sodium dihydrogen phosphate monohydrate, zinc acetate and manganese gluconate, cobalt acetate.
    The group of further additives relating to the present invention includes substances which improve the effectiveness and action of the synthetic camel organ extracts, for example by improving the shelf life, the solubility of the individual components, the buffering or effectiveness. The group of other additives includes Glucose, sorbitol, mannitol, citric acid, malic acid, succinic acid, benzyl alcohol, glycerin, ethanol, N-methylglucamine, sodium lactate and sodium succinate.
    In an alternative embodiment of the method according to the invention are used to produce the synthetic camel organ extracts
    a. 0.1-50 g / l, 2-10 g / l, or 4 g / l L-amino acids or L-amino acid derivatives,
    b. the peptide fraction resulting from 0.1-10 kg, from 1-5 kg, or from 2 kg, of camel organ tissue per liter of synthetic camel organ extract,
    c. 0.01-50 g / l, 0.1-5 g / l, or 1 g / l nucleic acid components and their derivatives,
    d. 0.1-1.0 g / l, 0.6-0.9 g / l, or 0.7 g / l vitamins and 0.1-20 g / l, 1-5 g / l, or 1.5 g / l mineral salts, as well
    e. and 0-200 g / l, 5-100 g / l, 80 g / l, 60 g / l or 20 g / l other additives, with 30-40 vol% water at a pH between 6.0 and 7, 4 mixed (weight-volume and volume / volume details refer to the synthetic camel organ extract final volume).
    [0037] In a further embodiment of the method according to the invention, the synthetic camel organ extracts are used to produce
    a. as L-amino acids or L-amino acid derivatives glycine, glutamic acid 0.3-0.4 g / l each, alpha-alanine, aspartic acid, hydroxyproline, proline, serine, lysine, arginine 0.2-0.4 g / l each, Histidine, ornithine, asparagine, valine, tyrosine, DL-threonine. Phenylalanine, leucine 0.03-0.06 g / l each, threonine, tryptophan, methionine β-alanine 0.01-0.03 g / l each, isoleucine, cysteine, creatinine, hippuric acid each <0.02 g / l , Urea 0.5-0.9 g / l,
    b. as a peptide fraction, per liter of synthetic camel organ extract, the peptide fraction resulting from 2 kg of camel organ tissue,
    c. as nucleic acid components and their derivatives, adenine, adenosine, cytidine, guanine, cytosine, uracil, guanosine, uridine, hypoxanthine, xanthine, cycl.AMP, adenosine monophosphate each 0.01-0.03 g / l, inosine 0.08 g / l , Uric acid and orotic acid each 0.02-0.03 g / l,
    d. as vitamins pyridoxol-HCI 0.5-0.7 g / l, biotin 0.1 g / l, thiamine chloride, calcium pantothenate, tocopherol succinate each <0.002 g / l, myo-inositol nicotine cream each <0.03 g / l , and as mineral salts magnesium sulfate, magnesium aspartate and sodium dihydrogen phosphate monohydrate each <0.07 g / l, zinc acetate 0.1 g / l, cobalt and manganese gluconate each 0.005 g / l.
    e. and as further additives glucose, sorbitol and mannitol each 0.1-0.5 g / l, citric acid 1-5 g / l, malic acid 1-2 g / l, succinic acid 5-15 g / l, ethanol 10-50 ml / l, benzyl alcohol 1-4 ml / l., glycerin 0.4-1.0 g / l, N-methylglucamine <0.5g / l, glucosamine 1.0-2.5 g / l, sodium lactate 1-4 g / l, Sodium succinate 2-15 g / l, mixed with 30-40 vol% water at a pH between 6.0 and 7.4 (values refer to the final volume).
    In an alternative embodiment of the invention, a special yeast cell preparation is added in the process for producing the synthetic camel organ extracts, which leads to a further increase in metabolic activity. An example of such a yeast cell preparation is H 38 (“75 Years Chemistry: Re-Reading”, Volume II, pages 448-449 (ISBN 978-1-882292-34-9). In a further alternative embodiment of the method according to the invention, 5 -500 ml / l, 10-150 ml / l, or 50 ml / l (based on the synthetic camel organ extracts final volume) H 38 yeast cell preparation added in yet another application form, a synthetic beef thymus extract can activate the cell metabolism activating Strengthen properties of camel organ extracts.
    In a further alternative embodiment of the invention, in addition to the peptide extract, the amino acids and nucleic acids and their derivatives, the vitamins, mineral salts, and the further additives, further components are admixed which enhance the activity of the camel organ extracts which increases cell metabolism activity. Components which increase the cell metabolism activity increasing effect of camel organ extracts include Carbohydrates and carbohydrate derivatives such as glucose, invert sugar, D-mannose, D-ribulose, L-erythrulose-1-phosphate, D-fructose-6-phosphate, D, L-arabinose and the N-methylhexosamine, aliphatic carboxylic acids with 3 to 6 carbon atoms and buffer substances.
    In a further embodiment of the invention, further components which increase metabolic activity are added to the synthetic camel organ extracts. The synthetic camel organ extracts according to the invention are effective substitutes or supplements for a large number of natural product extracts, in particular for natural or synthetic mammalian organ and plant extracts, in the form of placenta, thymus, blood, blood serum and spleen -, liver, heart muscle, elastin, collagen, connective tissue, amniotic fluid, umbilical cord, jellyfish and roe extracts and combinations thereof. The synthetic camel organ extracts according to the invention can be combined with such natural product extracts, for example natural or synthetic mammalian organ and plant extracts.
    Another aspect of the invention relates to the synthetic camel organ extracts produced by the method according to the invention. The composition and quality of the synthetic camel organ extracts can be validated with the aid of analytical methods customary in the prior art. Analytical parameters that can be tested in this way include pH, dry residue (5 h at 105 ° C), N content (according to Kjeldahl), amino acid determination: qualitatively using ninhydrin, using thin-layer chromatography (TLC) and HPLC; Detection of peptides: using a biuret reagent, freedom from proteins (using sulfosalicylic acid); Nucleic acid components: TLC; and sterility tests according to DAB 10.
    Table 1: Quality standard of protein-free, synthetic camel placenta extract (I, synthetic) [0042]
    Analytical data Camel placenta extract pH 6.7 - 7.5 dry matter 0.5-0.8% N 0.05-0.08% amino acids positive Peptides (biuret) positive Nucleic acid components positive hormones negative heavy metals <20 ppm sterility germ-free pyrogenicity non-pyrogenic BSE BSE-free
    According to a further aspect, the invention relates to the use of the synthetic camel organ extracts described above, individually or in the form of mixtures or combinations thereof with other collagen or other organ extracts from the camel and other organisms for the production of medical and pharmaceutical compositions , among other things for the strengthening of the immune system, for the activation of the cell metabolism or for the treatment of gastroenterological diseases, in particular ulcers, and for the topical, subcutaneous, intravenous or intramuscular application for the purpose of external or internal wound healing, for the treatment of arteriosclerosis or radiation damage , Another use of the synthetic camel organ extracts according to the invention is in the production of cosmetic formulations, such as, for example, cream formulations.
    The synthetic camel organ extracts can also be used individually or in the form of mixtures or combinations, undiluted or diluted, in the form of capsules containing them for direct oral intake, for example as a dietary supplement or food enhancer.
    Feed supplement for camels by synthetic camel organ extract application We found: a) Corresponding applications on young animals of camels that did not want to eat sufficiently: bad eater showed success some time after such treatment. Even such extracts had to be discontinued soon, since the bad eaters became over eater, b) The camel organ extracts were suitable as food supplements for camels that were convalescent c) Use of camel organ extracts as injection preparations : Appropriate experiments were carried out through the mediation of the Hamburg friend Wolfgang Seidel and also the former rector of the UFSM, Santa Maria Professor Jose Mariano da Rocha Filho, be carried out with camels of her friend sheikh: The sheikh has acquired the camel thymus extract made according to the inventor's recipe as an injectable solution a few years after his camels' successful racing.
    Just as the fermentation of normal baker's yeast can be increased by adding the metabolism-activating yeast preparations H 38 developed by the author, the organism of camels can also be increased in its activity by application of metabol6-activating camel organ extracts. This is of interest for racing camels or for camels in convalescence.
    The use of the synthetic camel organ extracts produced according to the invention, individually or in the form of mixtures or combinations thereof with other organ extracts, is not restricted to specific organisms. In one embodiment of the invention, the synthetic camel organ extracts according to the invention are applied to mammals; for example the human being, the camel, the horse, the cattle, the sheep, the chicken or the pig. In a further embodiment, the synthetic camel organ extracts according to the invention are applied to microorganisms or plants.
    Production of cream formulations (water / oil emulsions):
    Since 1965, the inventor has successfully implemented several protein-free (and enzyme-free) cosmetic additives, such as OMNITHYMUS, k-PFE + CELLRYL in EVANGYL (POLA).
    The justification for the use of protein-free organ extracts in cosmetic additives was given by the inventor in “75 Years Chemistry: Re-Reading”, Volume II, page 320 (ISBN 978-1-882292-34-9), as well as there on page 524 there is a comparison of normal, synthetic and cell culture extracts.
    According to the following composition, hand creams were formulated, to which synthetic extract I was added. The final composition of the cream formulations was as follows:
    Table 2
    component wt% Soluble lanolin derivative 1.0 acetylated lanolin alcohols 5.0 liquid multisterol extract 5.0 vaseline 5.0 Polyvinyl alcohol gel 0.75 10% NaOH 2.25 Test substances I (I, synthetic) 0.5 ethoxylated fatty amines 3.75 perfume oil 0.3 Water, double dist to 100% by weight (bidest: bidistilled)
    To prepare these cream formulations, the fat phase constituents and petroleum jelly were heated to approximately 75 ° C. At the same time, the PVA gel was dispersed in hot water at approx. 80 ° C and gradually dissolved. The ethoxylated fatty amine with about 25 EO units and possibly an emulsifier was added to the latter dispersion, after which the previously heated fat phase was emulsified therein. After stirring for 5 minutes at the mixing temperature, the mixture was cooled to 60 ° C., then the 10% sodium hydroxide solution was added and the mixture was cooled further to below 40 ° C. The formulations of the test solutions (synthetic extract I) were then added with slow stirring. The approach was well homogenized. The hand cream was made up stably and showed an improved skin conditioning compared to an approach without test substance addition.
    Camel connective tissue components (camel collagens) [0053] Production:
    After removal of blood, meat and fat, camel skin was crushed and then subjected to extraction with neutral salts or acids, depending on the target, in the freeze-dried state or as a solution (addition of sorbic acid for preservation) (see Dtsch.Apotheker-Ztg.117, 1557-62 (1977)). Comparable methods are described in the prior art for the production of other mammalian collagens.
    Camel collagen: N 18% + -0.3 hydroxyproline content: 14-15%.
    According to an alternative embodiment of the invention, the synthetic camel organ extracts produced by the process according to the invention are mixed with one or more camel connective tissue components. Examples of such connective tissue components are collagen types, elastins, fibronectins, creatines and hyaluronic acid.
    Examples Example 1
    Preparation of synthetic camel placenta extract (I, synthetic) as a 1 liter batch The following components, calculated to a final volume of 1 I, were stirred and under sterile conditions in a volume of bidist. H20 solved, which corresponds to 3/10 to 4/10 of the final volume. The pH was kept between 6.0 and 7.4:
    L-amino acids and derivatives:
    Glycine, glutamic acid 0.3-0.4 g each, a-alanine, aspartic acid, hydroxyproline, proline, serine, lysine, arginine 0.2-0.4 g each, histidine, ornithine, asparagine, valine, tyrosine, DL- threonine. Phenylalanine, leucine 0.03-0.06 g each, threonine, tryptophan, methionine β-alanine 0.01-0.03 g each, isoleucine, cysteine, creatinine, hippuric acid each <0.02 g, urea 0.5- 0.9 g.
    Peptide fraction from camel placenta glands:
    kg of thawed, blood-free glands and minced in a tooth colloid mill (to a size of 0.3 mm) were stored in 4 L ether + 300 ml ethanol in the cold room at -10 ° C for ten days, then separated in an explosion-proof drum centrifuge. By changing the osmotic conditions of the centrifugate (+ 150gNaCI) and simultaneously heating to 60 ° C, the proteins contained in the centrifugate split off peptides; then air was passed through, at pH 7.5 to remove the ether, and - after changing the pH to 3.4 with succinic acid - to remove residual proteins [ass through air or oxygen for a sufficient time: test with sulfosalicylic acidj. After Millipore filtration (pore size 0.22 micrometers), the peptide fraction required in the example was obtained (flow rate), the amount obtained from 10 kg of camel placenta glands being sufficient for 5 L of synthetic I extract, i.e. only 1/5 is used in the example. Nucleic Acid Components and Derivatives:
    Adenine, adenosine, cytidine, guanine, cytosine, uracil, guanosine, uridine, hypoxanthine, xanthine, cycl.AMP, adenosine monophosphate each 0.01-0.03 g, inosine 0.08 g, uric acid, orotic acid 0.02-0, 03 g.
    Vitamins:
    Pyridoxol-HCI 0.5-0.7 g, biotin 0.1 g, thiamine chloride, calcium pantothenate, tocopherol succinate each <0.002 g, myo-inositol nicotine cream each <0.03 g.
    Mineral Salts:
    Mg sulfate, Mg aspartate, NaH2P04-H20 each <0.07 g, Zn acetate: 0.1 g, Co, Mn gluconate each 0.005 g.
    [0061] Further additives:
    Glucose, sorbitol, mannitol 0.1-0.5 g each, citric acid 1-5 g, malic acid 1-2 g, succinic acid 5-15 g, ethanol 10-50 ml, benzyl alcohol 1-4 ml., Glycerin 0.4-1 / I, N-methylglucamine <0.5 g, Na lactate 1-4 g, Na succinate 2-15 g, sodium chloride 1-10 g, preservation possibly without.
    When preparing the solution, it should be noted that some components must be pre-dissolved and neutralized in NaOH or HCl, e.g. the amino acids Glu, Asp, Val, Tyr, Phe, Isoleu, Leu in 2N NaOH, xanthine in 3N NaOH, guanine in 3N HCl.
    After filling with bidist. Water was adjusted to 11 final volumes again the pH and sterile filtered.
    Example 2
    Synthetic extract I plus H 38 (later Y 20):
    The manufacturing process was carried out as indicated for Example 1. Before filling up to 1 l, 50 ml of H 38 (Y 20), a special yeast cell preparation, were added and the mixture was distilled. Replenished water to 11.
    The measured breathing increase factor was 2.6.
    Example 3
    PADBERG method:
    The Padberg test evaluates the absorption of methylene blue into the skin, the amount of absorption being related to the dryness of the skin. This is based on the observation that the absorption of methylene blue applied to the skin is proportional to skin dryness; so the higher the roughness, the more methylene blue is absorbed.
    For the implementation of the Padberg test usually 5-15 test persons aged 35-65 years are used. The test subjects are instructed not to use cosmetics on the skin areas to be examined for the test 3 days before the start and during the test. 6 test fields per test person are marked on the inside of each forearm, one of the test fields remains untreated. First, one for each test field
    Padberg test carried out to determine the blank value. The test subjects then apply the substance to be tested twice a day, morning and evening, to the test sites over a period of 14 days. Another Padberg test is carried out four hours after the last application.
    The Padberg test is carried out as for example in Journ. Soc. Cosmetic Chemicals 20, 719-728, [1969].
    Results of the PADBERG tests: Table 3 In Table 3 below, the photometer values for a cream composition with the addition of synthetic extract I or without (placebo cream) are expressed as a percentage of the value for treated skin and based on the initial value , summarized. Table 3 also shows the calculated mean values.
    The results show that smoothing of the skin can be achieved with the cream formulations with the addition of synthetic extract I. The same has also been shown when using a synthetic thymus extract as an additive.
    Table 3: Roughness test according to the PADBERG method with cream formulations (water / oil emulsions) with and without the addition of synthetic camel placenta extract (synthetic extract I) (duration of use 14 days).
    [0070]
    Subjects age Placebo-cream Cream formulations with the addition of I, synthetic 44 81.0 60.1 43 91.0 64.8 50 80.0 40.0 56 76.5 41.2 51 75.3 70.0 40 95.5 40.4 65 89.0 68.0 66 97.6 55.0 62 92.6 60.0 44 77.0 62.8 means 85.6 56.4
    Comparative Example 4 WARBURG method - test
    In a WARBURG apparatus, the metabolic activity of products, and in the case of the use of liver homogenate from rats or guinea pigs, the increase in breathing was determined by measuring the 02 uptake using manometric measurements. According to the filling plan, the side pears of the vessels were charged with test solution or water. The course of the reaction can be compared with and without product addition. The vessels were connected to the pressure gauges. The pressure gauges were hung in the thermostats and warmed up to the set temperature. Then test solution or water from the side vessel was introduced into the main vessel by tilting. This is the actual start of the reaction. The individual readings were taken at intervals of 10 minutes, the results are entered in the measurement plan. The Warburg trial lasts 90 minutes. The results provide the factors for increasing metabolic activity.
    Measurement plan
    Example: rye placenta extract with a factor of 1.83. Control: 1.0 (pre-incubation 1 h at 37 ° C):
    [0073]
    Table 4
    î: Y F 3 5  s ;.................... f 5 SaeoBoteewl. F *; 'F 0 ......... .........! I '^ Jî'7 FF · '- · j I.: Cï Si ï 0 Ma. 7 f ~ m : fc-1 x L, J l · / / - L - Ì -r --t • - 7; 'î ί '<·· - 1> - F 'F ~ * 7 y 3 r = -r F - r-f ·-1 -F -r -O - * · <’Z - c f FF - 1, --fit f > '· ·. ' - ’-C i .. f ', e.g. · 7 - ! 7r; > •.....:
    _____ ________: * ï, »» s j,,, ·! Γ j
    Table 5
    extract Warburg factor Rye placenta extract 1.83 control 1.0 Pig placenta extract 1.85 Bovine placenta extract 1.8
    Example 5 In an analogous manner to Comparative Example 4, respiratory increase factors were measured for synthetic extract I, synthetic extract II, synthetic camel liver extract and for camel NGF (Nerve Growth Promoting Factor)
    Table 6 [0076] extract Warburg factor synthetic extract 1 2.3 synthetic extract II 2.2-2.5 synthetic camel liver extract 2.3-2.4 Camel NGF 2.4
    During the BSE crisis, camel organ extracts, for example, were able to replace the undesirable bovine placenta extracts: Countries in which camels grow up were guaranteed to be BSE-free. The above-mentioned value for camel NGF is important: In clinical trials in Japan, camel NGF was successful in the treatment of facial paralsis. Previous results with NGF preparations from other animals have been reported in the author's “Re-Reading”, Volume II, page 295: ISBN 978-1-882292-34-9. Camel NGF was obtained by the method described there for other mammals: analysis data on Ve) of that regulation for camel NGF: yield: 1.8 g per kg of camel salivary gland, with a biological activity in BU of 0.010- 0.019 pg / g. Performing the biological identification and evaluation of camel NGF according to the information provided by Montalcini, Cancer Research 14, 49ff (1954) for the extraction and characterization of mouse NGF. When camel NGF was obtained from a camel's salivary gland, the literature refuted that there are no NGF factors in the salivary glands of large animals (collaboration with Prof. Dr. T. Yamamoto).
    By combination, e.g. with H 38 (later Y 20), a special yeast cell preparation (75 Years Chemistry-Re-Reading, Volume II (ISBN 978-1-828292), pages 448-449 and ref [11,14]), the activity of this can Continue extracting extract.
    Example 6 The results of activity tests for synthetic extract I and, for comparison, pig placenta extract are listed below, as well as indications of the working methods used:
    Table 7
    method Camel Placenta Synthetic (1) Pig Placenta Synthetic (1) PADBERG test (as above) 56.4 (85.6) 64.5 (88.9) Metamorphosis start shortening Xenopusl 5-8 days 3 to 4 days Wound healing (skin tension) 2 240 235
    Description of the methodology in “Re-Reading”, Part IV, p 448-456: IBSN 978-1-882292-36-3
    Methodology in "Cosmetics and Toiletries" 92, 25-27 (1977) Start of metamorphosis in the camel placenta synthetic I 5-8 days before control, whereas in pig placenta synthetic I 3-4 days before control (cf. Table 7 ).
    权利要求:
    Claims (10)
    [1]
    claims
    1. A method of making synthetic camel organ extracts comprising mixing
    a. one or more L-amino acids and / or derivatives thereof,
    b. a peptide fraction from a camel organ extract,
    c. one or more nucleic acid components and / or derivatives thereof,
    d. one or more vitamins and mineral salts, c. and optionally further additives, with 30-40% by volume of water at a pH between 6.0 and 7.4.
    [2]
    2. The method according to claim 1, wherein
    i) the L-amino acids and their derivatives are selected from the group comprising glycine, glutamic acid, alpha-alanine, aspartic acid, hydroxyproline, proline, serine, lysine, arginine, histidine, ornithine, asparagine, valine, tyrosine,
    DL-threonine, phenylalanine, leucine, threonine, tryptophan, methionine, β-alanine, isoleucine, cysteine, creatinine and hippuric acid.
    ii) the nucleic acid components and their derivatives are selected from the group comprising adenine, adenosine, cytidine, guanine, cytosine, uracil, guanosine, uridine, hypoxanthine, xanthine, cycl. AMP, adenosine monophosphate, inosine, uric acid and orotic acid iii) vitamins and mineral salts are selected from the group consisting of pyridoxol-HCl, biotin, thiamine, calcium pantothenate, tocopherol succinate, myo-inositol, nicotinamide, magnesium sulfate, magnesium aspartate, sodium dihydrogen phosphate monohydrate, zinc acetate, Cobaltgluconat and manganese gluconate, and iv) the further additives are selected from the group comprising glucose, sorbitol, mannitol, citric acid, malic acid, succinic acid, benzyl alcohol, glycerol, ethanol, N-methylglucamine, sodium lactate and sodium succinate.
    [3]
    3. The method according to claim 1 or 2, wherein to maintain the peptide fraction from camel organs b1) blood-free and washed camel organ tissue is mechanically crushed to a slurry and mixed with one or more suitable solvent (s) or solvent mixture, b2) this mixture for several days stored refrigerated and then centrifuged, b3) the peptides contained in the centrifugate are split off in the centrifugate by changing the osmotic conditions and simultaneously heating to 55-65 ° C., b4) the pH is lowered to 3.2 to 3.5 remove the remaining proteins b5) and finally filter sterile.
    [4]
    4. The method according to any one of claims 1 to 4, wherein a yeast cell preparation is also admixed.
    [5]
    5. The method according to any one of claims 1 to 4, wherein further components are added, which enhance the cell metabolism activity increasing effect of the camel organ extracts and / or have their own metabolism activity increasing effect.
    [6]
    6. The method according to any one of claims 1 to 5, wherein further natural or synthetic mammalian organ extracts are added to the synthetic camel organ extracts.
    [7]
    7. Synthetic camel organ extracts and extract mixtures, such as those obtainable by the process according to one of claims 1 to 6.
    [8]
    8. Use of the synthetic camel organ extracts and extract mixtures according to one of claims 1 to 6 for the manufacture of a medicinal composition for topical, subcutaneous, intravenous or intramuscular use for the purpose of external or internal wound healing, for the treatment of arteriosclerosis or radiation damage.
    [9]
    9. Use of the synthetic camel organ extracts and extract mixtures, as are obtainable by the process according to at least one of claims 1 to 6, as cosmetic additives or as food enhancers.
    [10]
    10. The method according to any one of claims 1 to 6, wherein the synthetic camel organ extracts are mixed with one or more camel connective tissue components, selected from the group comprising collagen types, elastins, fibronectins, creatines and hyaluronic acid.
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    同族专利:
    公开号 | 公开日
    CH713107B1|2021-04-30|
    DE112016007409A5|2019-08-01|
    WO2018082795A1|2018-05-11|
    JP2019532987A|2019-11-14|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    AT157880T|1991-12-02|1997-09-15|Riemschneider Randolph Dr Dr P|AQUEOUS SYNTHETIC ORGAN EXTRACTS|CN112675159A|2021-01-12|2021-04-20|杭州师范大学|Application of L-malic acid in preparing medicine for preventing and treating liver ischemia reperfusion injury|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    CH01466/16A|CH713107B1|2016-11-04|2016-11-04|Synthetic camel organ extracts, process for their production and their use.|CH01466/16A| CH713107B1|2016-11-04|2016-11-04|Synthetic camel organ extracts, process for their production and their use.|
    JP2019522946A| JP7022126B2|2016-11-04|2016-11-29|Synthetic camel organ extract, its manufacturing method and its use|
    DE112016007409.3T| DE112016007409A5|2016-11-04|2016-11-29|SYNTHETIC CAMEL ORGAN EXTRACTS, PROCESS FOR THEIR PREPARATION AND THEIR USE|
    PCT/EP2016/079098| WO2018082795A1|2016-11-04|2016-11-29|Synthetic camel organ extracts, method for the preparation and use thereof|
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