CH713107B1 - Synthetic camel organ extracts, process for their production and their use. - Google Patents
Synthetic camel organ extracts, process for their production and their use. Download PDFInfo
- Publication number
- CH713107B1 CH713107B1 CH01466/16A CH14662016A CH713107B1 CH 713107 B1 CH713107 B1 CH 713107B1 CH 01466/16 A CH01466/16 A CH 01466/16A CH 14662016 A CH14662016 A CH 14662016A CH 713107 B1 CH713107 B1 CH 713107B1
- Authority
- CH
- Switzerland
- Prior art keywords
- camel
- acid
- synthetic
- organ
- derivatives
- Prior art date
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Abstract
Verfahren zur Herstellung von synthetischen Kamel-Organ Extrakten, die mit dem erfindungsgemäßen Verfahren hergestellten Extrakte sowie deren Verwendung allein und als Bestandteil von kosmetischen, und diätetischen Zusammensetzungen.Process for the production of synthetic camel organ extracts, the extracts produced with the process according to the invention and their use alone and as a component of cosmetic and dietetic compositions.
Description
[0001] Tierische Organextrakte haben als Grundstoffe für Pharmaka und Kosmetika eine große Bedeutung. Insbesondere tierische Plazenta-Extrakte werden aufgrund der darin enthaltenden Wirkstoffe in Pharmaka und Kosmetika in großem Umfang eingesetzt [vgl.„Seifen-Öle-Fette-Wachse“112, 211-218 (1986)], wobei sie in vielen Fällen gegebenenfalls noch durch niedermolekulare Zusätze ergänzt werden. Animal organ extracts are of great importance as raw materials for pharmaceuticals and cosmetics. Animal placenta extracts, in particular, are used on a large scale in pharmaceuticals and cosmetics because of the active ingredients they contain [cf. “Seifen-Öle-Fette-Wachse” 112, 211-218 (1986)] Supplements are added.
[0002] Das genügsame Kamel wird zunehmend bedeutender als Viehbestand, bedingt a) durch den Klimawandel, der zu einer Zunahme der Wüstengegenden unserer Erde führt, b) durch das unregulierbare Wachstum unserer Erdbevölkerung, deren Ernährung irgendwann in Frage gestellt wird, wenn wir so weitermachen wie bisher (z.B. zu aufwendige Schweine- und Rinderzucht). Zur Familie der Kamele gehören: Kamel (300-950kg) mit zwei Höckern (Asien), Dromedar (300-500kg) mit einem Höcker (Afrika), Lama, Alpacka, Guanaco, Vikunja. Die Höcker sind Fettreservoire. 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) due to the unregulated growth of our earth's population, whose diet will at some point be questioned if we continue like this as before (e.g. too expensive pig and cattle breeding). The camel family includes: camel (300-950kg) with two humps (Asia), dromedary (300-500kg) with one hump (Africa), lama, alpacka, guanaco, vicuna. The humps are fat reserves.
[0003] Seit 1947 hat der Erfinder das Kamel in seine Forschungen über tierische Organextrakte von Schwein, Rind, Pferd mit eingeschlossen, und hat z.B. auch natürliche Kamel-Plazenta-Extrakt (I) und Kamel-Thymus-Extrakt (II) hergestellt und deren Zusammensetzung genau analysiert, um damit die Voraussetzungen für die Entwicklung von entsprechendem proteinfreiem, synthetischem Extrakt I (I, synthetisch) und II (II, synthetisch) zu schaffen. Ein Vorläufer zu I und II war das vom Erfinder entwickelte synthetische Injektionspräparat CELLRYL, Japan (Basis: Kälberblut SR 71), das sich bereits durch Zellstoffwechsel-aktivierende Eigenschaften auszeichnete: Steigerung der ATP-Produktion in den Mitochondrien, messbar mittels WARBURG-Methodik, mit Steigerungsfaktor um 1,8. Since 1947, the inventor has included the camel in his research on animal organ extracts from pigs, cattle, horses, and has also produced natural camel placenta extract (I) and camel thymus extract (II), for example, and their Composition carefully analyzed in order to create the conditions for the development of corresponding protein-free, synthetic extracts 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 Increase factor by 1.8.
[0004] Aufgabe der vorliegenden Erfindung ist somit die Bereitstellung eines Verfahrens zur Herstellung von synthetischen Kamel-Organ-Extrakten, sowie die daraus resultierenden synthetischen Kamel-Organ-Extrakte, die das biochemische Wirkungsprofil der bekannten natürlichen und synthetischen tierischen Organextrakte vorzugsweise wesentlich verbessern. The object of the present invention is thus to provide a method for the production of synthetic camel organ extracts, and the resulting synthetic camel organ extracts, which preferably improve the biochemical activity profile of the known natural and synthetic animal organ extracts.
[0005] Diese Aufgabe wird durch die vorliegende Erfindung gelöst. Die durch das erfindungsgemäße Verfahren hergestellten synthetischen Kamel-Organ-Extrakte zeichnen sich unter anderem durch ihre verbesserte Zellstoffwechsel-aktivierenden Eigenschaften aus und finden in vielen Bereichen des Alltags Anwendung, einschließlich als Additive für Kosmetika (beispielsweise in Hautcremen) oder als Nahrungsmittelergänzung. This object is achieved by the present invention. The synthetic camel organ extracts produced by the process according to the invention are distinguished, among other things, by their improved cell metabolism-activating properties and are used in many areas of everyday life, including as additives for cosmetics (for example in skin creams) or as food supplements.
Zusammenfassung der ErfindungSummary of the invention
[0006] Zur Lösung der vorliegenden Aufgabe wird (1) ein Verfahren zur Herstellung von synthetischen Kamel-Organ-Extrakten bereitgestellt, umfassend das Mischen a. von einer oder mehreren L-Aminosäuren und deren Derivaten, b. einer Peptidfraktion aus einem Kamel-Organ-Extrakt, c. von einer oder mehreren Nucleinsäurekomponenten und deren Derivaten, d. und von einem oder mehreren Vitaminen und Mineralsalzen,To achieve the present object (1) a process for the production of synthetic camel organ extracts is provided, comprising 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. and of one or more vitamins and mineral salts,
[0007] (2) Verfahren gemäß Punkt 1, wobei die L-Aminosäuren und deren Derivate ausgewählt werden aus der Gruppe umfassend Glycin, Glutaminsäure, alpha-Alanin, Asparaginsäure, Hydroxyprolin, Prolin, Serin, Lysin, Arginin, Histidin, Ornithin, Asparagin, Valin, Tyrosin, DL-Threonin, Phenylalanin, Leucin, Threonin, Tryptophan, Methionin, β-Alanin, Isoleucin, Cystein, Kreatinin und Hippursäure. (3) Verfahren gemäß Punkt 1 oder 2, wobei zur Erhaltung der Peptidfraktion aus Kamelorganen, b1) blutfreies und gewaschenes Kamelorgangewebe mechanisch zu einem Brei zerkleinert und mit einem passenden Lösungsmittel, oder Lösungsmittelgemisch versetzt wird, b2) dieses Gemisch während mehrerer Tage gekühlt gelagert, und anschließend zentrifugiert wird, b3) im Zentrifugat durch Änderung der osmotischen Bedingungen und gleichzeitiges Erwärmen auf 55-65°C Peptide von den vorhandenen Proteinen abgespalten werden, b4) der pH auf 3,2 bis 3,5 abgesenkt wird, um durch ausreichend langes Ausleiten von Luft oder Sauerstoff restliche Proteine zu entfernen b5) und schließlich steril filtriert wird. (4) Verfahren gemäß einem der Punkte 1-3, wobei es sich bei dem passenden Lösungsmittelgemisch um einen Ether und Ethanol handelt und nach Schritt b3) zur Entfernung des Ethers, bei einem pH von 7,2 bis 7,5, ein Luftgemisch durch das Zentrifugat durchgeleited wird. (5) Verfahren gemäß einem der Punkte 1-4, wobei die Peptidfraktion aus einem Kamel-Planzenta-Extrakt, Kamel-Thymus-Extrakt oder einem Kamel-Leber-Extrakt erhalten wird. (6) Verfahren gemäß einem der Punkte 1-5, wobei die Nucleinsäurekomponenten und deren Derivate ausgewählt werden aus der Gruppe umfassend Adenin, Adenosin, Cytidin, Guanin, Cytosin, Uracil, Guanosin, Uridin, Hypoxanthin, Xanthin, cycl. AMP, Adenosinmonophosphat, Inosin, Harnsäure und Orotsäure. (7) Verfahren gemäß einem der Punkte 1-6, wobei die Vitamine und Mineralsalze ausgewählt werden aus der Gruppe umfassend Pyridoxol-HCI, Biotin, Thiaminchlorid, Calciumpantothenat, Tocopherolsuccinat, myo-Inosit, Nicotinamid, Magnesiumsulfat, Magnesiumaspartat, Natriumdihydrogenphosphat-Monohydrat, Zinkacetat, Cobaltgluconat und Mangangluconat. (8) Verfahren gemäß einem der Punkte 1-7, wobei weitere Zusätze auszuwählen sind aus der Gruppe umfassend Glukose, Sorbit, Mannit, Zitronensäure, Äpfelsäure, Bernsteinsäure, Benzylalkohol, Glyzerin, Ethanol, N-Methylglucamin, Glukosamin, Natriumlactat und Natriumsuccinat. (9) Verfahren gemäß einem der Punkte 1-8 wobei zur Herstellung der synthetischen Kamel-Organ-Extrakte a. 0,1-50 g/l, 2-10 g/l, oder 4 g/l L-Aminosäuren oder L-Aminosäurederivate, b. die sich aus 0,1-10 kg, aus 1-5 kg, beziehungsweise aus 2 kg, Kamel-Organgewebe ergebende Peptidfraktion pro Liter synthetisches Kamel-Organ-Extrakt, c. 0,01-50 g/l, 0,1-5 g/l, oder 1,0 g/l Nucleinsäurekomponenten und deren Derivate, d. 0,1-1,0 g/l, 0,6-0,9 g/l, oder 0,7g/l Vitamine und 0,1-20 g/l,1-5 g/l, oder 1,5g/l Mineralsalze, sowie e. und 0-200 g/l, 5-100 g/l, 80 g/l, 60 g/l oder 20 g/l weitere Zusätze, mit 30-40 Vol-% Wasser bei einem pH zwischen 6,0 und 7,4 vermischt werden. (Gewicht/Volumen und Volumen/Volumen Angaben beziehen sich auf das synthetische Kamel-Organ-Extrakt Endvolumen). (10) Verfahren gemäß einem der Punkte 1-9, wobei zur Herstellung der synthetischen Kamel-Organ-Extrakte a. als L-Aminosäuren oder L-Aminosäurederivate Glycin, Glutaminsäure je 0,3-0,4 g/l, alpha-Alanin, Asparaginsäure, Hydroxyprolin, Prolin, Serin, Lysin, Arginin je 0,2-0,4 g/l, Histidin, Ornithin, Asparagin, Valin, Tyrosin, DL-Threonin. Phenylalanin, Leucin je 0,03-0,06 g/l, Threonin, Tryptophan, Methionin β-Alanin je 0,01-0,03 g/l, Isoleucin, Cystein, Kreatinin, Hippursäure je <0,02 g/l, Urea 0,5-0,9 g/l, b. als Peptidfraktion, pro Liter synthetisches Kamel-Organ-Extrakt, die sich aus 2 kg Kamel-Organgewebe ergebende Peptidfraktion, c. als Nucleinsäurekomponenten und deren Derivate, Adenin, Adenosin, Cytidin, Guanin, Cytosin, Uracil, Guanosin, Uridin, Hypoxanthin, Xanthin, cycl.AMP, Adenosinmonophosphat je 0,01-0,03 g/l, Inosin 0,08 g/l, Harnsäure und Orotsäure je 0,02-0,03 g/l, d. als Vitamine Pyridoxol-HCI 0,5-0,7 g/l, Biotin 0,1 g/l, Thiaminchlorid, Ca-pantothenat, Tocopherolsuccinat je <0,002 g/l, myo-Inosit Nicotinsreamid je <0,03 g/l, und als Mineralsalze Magnesiumsulfat, Magnesiumaspartat und Natriumdihydrogenphosphat-Monohydratje <0,07 g/l, Zinkacetat 0,1 g/l, Cobalt-, Mangangluconatje 0,005 g/l. e. und als weitere Zusätze Glukose, Sorbit und Mannitje 0,1-0,5 g/l, Zitronensäure 1-5 g/l, Äpfelsäure 1-2 g/l, Bernsteinsäure 5-15 g/l, Ethanol 10-50 ml/l, Benzylalkohol 1-4 ml/l., Glyzerin 0.4-1.0 g/l, N-Methylglucamin <0,5g/l, Glukosamin 1-2,5 g/l, Natriumlactat 1-4 g/l, Natriumsuccinat 2-15 g/l, mit 30-40 Vol-% Wasser bei einem pH zwischen 6,0 und 7,4 vermischt werden (Werte beziehen sich auf das Endvolumen). (11) Verfahren gemäß einem der Punkte 1-10, wobei außerdem eine Hefezellpräparation beigemischt wird. (12) Verfahren gemäß einem der Punkte 1-11, wobei weitere Komponenten beigemischt werden, welche die zellstoffwechselaktivitätssteigernde Wirkung der Kamel-Organ-Extrakte verstärken und/oder eine stoffwechselaktivitätssteigernde Wirkung anfweisen, ausgewählt aus der Gruppe bestehend aus Kohlen hydraten und kohlenhydratderivaten, wie beispielsweise Glucose, Invertzucker, D-Mannose, D-Ribulose, L-Erythrulose-1–phosphat, D-Fructose-6–phosphat, D.L-Arabinose, N-Methylhexosamin, aliphatische Carbonsäuren mit 3 bis 6 Kohlenstoffatomen und Puffersubstanzen. (13) Verfahren gemäß einem der Punkte 1-12, wobei den synthetischen Kamel-Organ-Extrakten weitere natürliche oder synthetische Säugetier-Organ-Extrakte beigemischt werden. (14) Verfahren gemäß einem der Punkte 1-13, wobei den synthetischen Kamel-Organ-Extrakten weitere natürliche oder synthetische Pflanzen-Extrakte beigemischt werden. (15) Synthetische Kamel-Organ-Extrakte und -Extraktgemische, wie sie nach dem Verfahren nach einem der Punkte 1-14 erhältlich sind. (16) Verfahren gemäß einem der Punkte 1-14, wobei die synthetischen Kamel-Organ-Extrakte mit einer oder mehreren Kamel-Bindegewebs-Komponenten vermischt werden. (17) Verfahren gemäß Punkt 16, wobei die Kamel-Bindegewebs-Komponenten auszuwählen sind aus der Gruppe umfassend Kollagen-Typen, Elastine, Fibronektine, Kreatine und Hyaluronsäure.(2) The 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) Process according to point 1 or 2, whereby in order to preserve the peptide fraction from camel organs, b1) blood-free and washed camel organ tissue is mechanically pulverized and mixed with a suitable solvent or solvent mixture, b2) this mixture is stored in a cool place for several days, 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 in order to by sufficiently long Discharge of air or oxygen to remove residual proteins b5) and finally sterile filtering. (4) Process according to one of items 1-3, the suitable solvent mixture being an ether and ethanol and, after step b3), an air mixture to remove the ether at a pH of 7.2 to 7.5 the centrifugate is passed through. (5) The method according to any one of items 1-4, wherein the peptide fraction is obtained from a camel plantenta 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, wherein the vitamins and mineral salts are selected from the group comprising pyridoxol-HCl, biotin, thiamine chloride, calcium pantothenate, tocopherol succinate, myo-inositol, nicotinamide, magnesium sulfate, magnesium aspartate, sodium dihydrogen phosphate monohydrate, zinc acetate , Cobalt gluconate and manganese gluconate. (8) Method according to one of points 1-7, further additives being selected from the group comprising glucose, sorbitol, mannitol, citric acid, malic acid, succinic acid, benzyl alcohol, glycerine, ethanol, N-methylglucamine, glucosamine, sodium lactate and sodium succinate. (9) Process according to any one of items 1-8, wherein 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, 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, or 0.7g / l vitamins and 0.1-20 g / l, 1-5 g / l, or 1.5g / l mineral salts, as well as 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% by volume of water at a pH between 6.0 and 7, 4 to be mixed. (Weight / volume and volume / volume data refer to the synthetic camel organ extract final volume). (10) The method according to any one of items 1-9, wherein for the preparation of the synthetic camel organ extracts a. as L-amino acids or L-amino acid derivatives glycine, glutamic acid each 0.3-0.4 g / l, alpha-alanine, aspartic acid, hydroxyproline, proline, serine, lysine, arginine each 0.2-0.4 g / l, 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 <0.02 g / l each , 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 <0.002 g / l each, myo-inositol nicotine creamid <0.03 g / l each , 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., glycerine 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% by volume of water at a pH between 6.0 and 7.4 (values refer to the final volume). (11) The method according to any one of items 1-10, wherein a yeast cell preparation is also admixed. (12) Method according to one of items 1-11, further components being added which increase the cell metabolic activity-increasing effect of the camel organ extracts and / or have a metabolic activity-increasing effect, selected from the group consisting of carbohydrates and carbohydrate derivatives, such as, for example Glucose, invert sugar, D-mannose, D-ribulose, L-erythrulose-1-phosphate, D-fructose-6-phosphate, DL-arabinose, N-methylhexosamine, aliphatic carboxylic acids with 3 to 6 carbon atoms and buffer substances. (13) Method according to one of items 1-12, further natural or synthetic mammalian organ extracts being admixed with the synthetic camel organ extracts. (14) Method according to one of items 1-13, further natural or synthetic plant extracts being added to the synthetic camel organ extracts. (15) Synthetic camel organ extracts and extract mixtures, as they can be obtained by the method according to one of the items 1-14. (16) The method according to any one of items 1-14, wherein the synthetic camel organ extracts are mixed with one or more camel connective tissue components. (17) Method according to point 16, wherein the camel connective tissue components are to be selected from the group comprising collagen types, elastins, fibronectins, creatines and hyaluronic acid.
Detaillierte Beschreibung der ErfindungDetailed description of the invention
[0008] Gemäß einem ersten Aspekt der vorliegenden Erfindung wird ein Verfahren zur Herstellung von synthetischen Kamel-Organ-Extrakten bereitgestellt. Dabei werden eine oder mehrere L-Aminosäuren und deren Derivate, eine Peptidfraktion aus einem Kamel-Organ-Extrakt, eine oder mehrere Nucleinsäurekomponenten und deren Derivate, ein oder mehrere Vitamine und Mineralsalze sowie optional weiteren Zusätzen, mit 30-40 Vol-% (Volumenprozent) Wasser, vorzugsweise bidestilliert (bidest.), bei einem pH zwischen 6,0 und 7,4 gelöst bzw. vermischt. Die einzelnen Komponenten werden unter Rühren und sterilen Bedingungen vermischt. According to a first aspect of the present invention, a method for producing synthetic camel organ extracts is provided. 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, at 30-40% by volume (volume percent ) Water, preferably double-distilled (double-distilled), dissolved or mixed at a pH between 6.0 and 7.4. The individual components are mixed with stirring and under sterile conditions.
[0009] Gemäß der vorliegenden Erfindung ist die Gruppe der L-Aminosäuren und L-Aminosäurederivate nicht weiter beschränkt. In einer Ausführungsform der Erfindung sind geeignete L-Aminosäuren und L-Aminosäurederivate Asparagin, Asparaginsäure, Cystein, Cystin, Glutaminsäure, Glutamin, alpha-Alanin, beta-Alanin, Arginin, Glycin, Histidin, delta-Hydroxylysine, Hydroxyproline, Leucin, Isoleucin, Lysin, Methionin, Norleucin, Phenylalanin, Prolin, Serin, Threonin, Tryptophan, Tyrosin, Valin, alpha-Aminoadipinsäure, alpha-Aminobuttersäure (normal), gamma-Amino-n-buttersäure, beta-Amino-isobuttersäure, delta-Aminolävulinsäure, Carbamylasparaginsäure, Citrullin, Kreatin, Kreatinin, Cystathionin, Cysteinsäure, Ergothionein (Betain des Thiolhistidins), Glycocyamin (Guinidinessigsäure), Homoserin, Ornithin, Taurin, Djenkolsäure (Cysteinthioformacetal), Guanidinsalze, Ornithursäure, Phenacetursäure, Hippursäure, Harnstoff, N-Acetyl-L-alanin, N-Acetyl-L-arginin, N-Acetylglycin, N-Acetyl-L-hydroxyprolin, N-Acetyl-L-isoasparagin, N-Acetyl-L-isoleucin, N-Acetyl-L-leucin, N-Acetyl-L-lysin, N-Acetyl-L-methionin, N-Acetylmuraminsäure, N-Acetyl-L-ornithin, N-Acetyl-L-phenylalanin, N-Acetyl-L-prolin, 0-Acetyl-L-serin, N-Acetyl-L-threonin, N-Acetyl-L-tryptophan, N-Acetyl-L-valin, L-allo-Isoleucin , L-allo-Threonin, N-Benzoyl-L-arginin, N-Benzoyl-L-histidin, N-Benzoyl-L-lysin, N-Benzoyl-L-methionin, N-Benzoyl-L-ornithin, N-Benzoyl-L-phenylalanin, N-Benzoyl-L-tryptophan, N-Benzoyl-L-valin, S-Benzoyl-L-cystein, O-Benzoyl-L-serin, O-Benzoyl-L-tyrosin, L-Carnosin (β-Alanyl-L-histidin), N,O-Diacetyl-L-threonin und O-Phospho-L-serin. According to the present invention, the group of L-amino acids and L-amino acid derivatives is not restricted further. 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, cysteic acid, ergothioneine (betaine des thiolhistidine), glycocyamine (guinidine acetic acid), homoserine, ornithine, taurine, djenkolic acid (cysteine thioformacetal), guanidine salts, ornithuric acid, phenacetylic acid 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-methionine, N-acetylmura minic acid, N-acetyl-L-ornithine, N-acetyl-L-phenylalanine, N-acetyl-L-proline, 0-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, N-benzoyl-L-phenylalanine, N-benzoyl-L-tryptophan, N-benzoyl-L-valine, S-benzoyl-L-cysteine, O-benzoyl-L-serine, O-benzoyl-L-tyrosine, L-carnosine (β-alanyl-L-histidine), N, O-diacetyl-L-threonine and O-phospho-L-serine.
[0010] In einer alternativen Ausführungsform der Erfindung besteht die Gruppe von geeigneten L-Aminosäuren und L-Aminosäurederivaten aus Glycin, Glutaminsäure, alpha-Alanin, Asparaginsäure, Hydroxyprolin, Prolin, Serin, Lysin, Arginin, Histidin, Ornithin, Asparagin, Valin, Tyrosin, DL-Threonin, Phenylalanin, Leucin, Threonin, Tryptophan, Methionin, β-Alanin, Isoleucin, Cystein, Kreatinin und Hippursäure. In an alternative embodiment of the invention, the group of suitable L-amino acids and L-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.
[0011] Gemäß der vorliegenden Erfindung wird eine Peptidfraktion aus Kamelorganen wie folgt erhalten. Blutfreies und gewaschenes Kamelorgangewebe wird mechanisch zu einem Brei zerkleinert und mit einem oder mehreren passenden Lösungsmittel vermischt, während mehrerer Tage, z.B. 5, 10 oder 15 Tage, gekühlt (vorzugsweise bei < -10°C) aufbewahrt, und anschließend durch Zentrifugieren (beispielsweise mit einer explosionssicheren Trommelzentrifuge) getrennt. Ein passendes Lösungsmittelgemisch ist z.B. ein Ether und Ethanol, vorzugsweise im Verhältnis 13.3 : 1. Unter Änderung der osmotischen Bedingungen des Zentrifugates und gleichzeitigem Erwärmen auf ca. 60°C spalten sich aus den im Zentrifugat enthaltenen Proteinen Peptide ab. Anschließend kann bei einem pH von 7,2 bis 7,5 Luft durchgeleitet werden zur Entfernung des Lösungsmittels (Ethers). Der pH wird anschließend auf ca. 3,4 abgesenkt, um durch Luft- oder Sauerstoff-Durchleitung restliche Proteine zu entfernen. Proteinfreiheit kann mit Sulfosalicylsäure festgestellt werden. Nach Sterilfiltration (Porenweite 0,22 µm) wird die erforderliche Peptidfraktion (Durchfluss) erhalten. According to the present invention, a peptide fraction from camel organs is obtained as follows. Blood-free and washed camel organ tissue is mechanically crushed to a pulp and mixed with one or more suitable solvents, kept refrigerated (preferably at <-10 ° C) for several days, e.g. 5, 10 or 15 days, and then centrifuged (e.g. 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. When the osmotic conditions of the centrifugate are changed and the centrifugate is heated to about 60 ° C, peptides are split off from the proteins contained in the centrifugate. Then air can be passed through at a pH of 7.2 to 7.5 to remove the solvent (ether). The pH is then lowered to approx. 3.4 in order to remove residual proteins by passing air or oxygen through them. Free from protein can be determined with sulfosalicylic acid. After sterile filtration (pore size 0.22 µm), the required peptide fraction (flow-through) is obtained.
[0012] Unter Kamelorgan oder Kamelorgangewebe gemäß der vorliegenden Erfindung ist jedes aus einem Kamel stammende Organ oder Teil eines Organs (Organgewebe) zu verstehen. In einer alternativen Ausführungsform der Erfindung handelt es sich bei dem Kamelorgan oder Kamelorgangewebe um Plazenta, Thymusdrüse, Leber, Milz, Herzmuskel, Bindegewebe, oder Speicheldrüse. In einer bevorzugten Ausführungsform der Erfindung handelt es sich bei dem Kamelorgan oder Kamelorgangewebe um Kamelplazenta, Kamelthymusdrüse, Kamelleber, oder Kamelspeicheldrüse. In einer weiteren bevorzugten Ausführungsform der Erfindung handelt es sich bei dem Kamelorgan oder Kamelorgangewebe um Kamelplazenta oder Kamelthymusdrüse. Under camel organ or camel organ tissue according to the present invention, any organ or part of an organ (organ tissue) originating from a camel is to be understood. In an alternative embodiment of the invention, the camel organ or camel organ tissue is placenta, thymus gland, 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, camel liver, or camel pancreas. In a further preferred embodiment of the invention, the camel organ or camel organ tissue is camel placenta or camel thymus.
[0013] Die Gruppe der Nucleinsäurekomponenten und Nucleinsäurederivate gemäß der vorliegenden Erfindung ist nicht weiter limitiert. Beispiele von Nucleinsäurekomponenten und deren Derivate sind 2-Aminopurin, Hypoxanthin, 1-Methylhypoxanthin, Adenin, 2-Methyladenin, 6-Methylaminopurin, Guanin, 1-Methylguanin, 7-Methylguanin, 2-Methylamino-6-oxodihydropurin, 8-Hydroxyguanin, Isoguanin, 2,6-Diaminopurin, Xanthin, 1-Methylxanthin, 3-Methylxanthin, 7-Methylxanthin, 3,9-Dimethylxanthin, Harnsäure, 1-Methylharnsäure, 9-Methylharnsäure, 1,9-Dimethylharnsäure, 3,7-Dimethylharnsäure, 1,3,7-Trimethylharnsäure, Adenosin, 3'-Amino-3'-desoxy-adenosin, 9-β-D-Ribofuranosyl-6-methylaminopurin, 2'-Desoxyinosin, 2'-Adenylsäure, 3'-Adenylsäure, 5'-Adenylsäure, Adenosin-5'-diphosphorsäure, Adenosin-5'-triphosphorsäure, Desoxyadenylsäure, 2'-Desoxyadenosin-5'-triphosphat, N-Succinyladenylsäure, 3'-Guanylsäure, Guanosin-5'-diphosphorsäure, Guanosin-5'-triphosphorsäure, Inosin-3'-phosphorsäure, lnosin-5'-phosphorsäure, Inosin-5'-diphosphorsäure, Xanthylsäure, Xanthosin-5'-monophosphorsäure, Guanosindiphosphatmannose, Guanosindiphosphat-fructose, Guanosindiphosphat-fucose, Diphosphopyridinnucleotid, Triphosphopyridinnuelotid, Cytosin, 5-Methylcytosin, 5-Hydroxymethylcytosin, Cytimidin, Thymin, Uracil, Willardiin, 5-Aminouracil, 4,5-Dihydrouracil, 4-Aminouracil, Uridin, 4,5-Dihydrouridin, 2'-Desoxyuridin, 5-Methyluridin, Pseudouridin, Orotidin, Cytidin, 2'-Desoxycytidin, 5-Methylcytidin, Thymidin, a-Thymidin, Cytidin-2'-monophosphat, Cytidin-3'-monophosphat, Cytidin-5'-monophosphat, Cytidin-5'-diphosphat, Uridin-2'-monophosphat, Uridin-3'-monophosphat, Orotsäure, Uridin-5'-monophosphat, Uridin-5'-diphosphat, 5-Methylcytidin-3'-monophosphat, Orotidin-5'-monophosphat, Thymidin-5'monophosphat, Thymidin-5'-triphosphat, 2'-Desoxycytidin-5'monophosphat, 2'-Desoxycytidin-5-diphosphat, Uridindiphosphat-glucose, Uridindiphosphatgalaktose, Uridindiphosphat-arabinose, Uridindiphosphat-xylose, Uridindiphosphat-glucuronsäure, Uridindiphosphat-N-acetylgalaktosamin, Cytidindiphosphat-a-glycerin, Cytidindiphosphatribitol, cycl. AMP, cycl. GMP u.a. The group of nucleic acid components and nucleic acid derivatives according to the present invention is not limited further. 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-hydroxyguanine, isoguanine , 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-β-D-ribofuranosyl-6-methylaminopurine, 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 mannose, guanosine-diphosphate-fr uctose, guanosine diphosphate fucose, diphosphopyridine nucleotide, triphosphopyridine nuelotide, cytosine, 5-methylcytosine, 5-hydroxymethylcytosine, cytimidine, thymine, uracil, willardiine, 5-aminouracil, 4,5-dihydrouridine, 4,5-dihydrouracil, 4-aminouracil 2'-deoxyuridine, 5-methyluridine, pseudouridine, orotidine, cytidine, 2'-deoxycytidine, 5-methylcytidine, thymidine, α-thymidine, cytidine-2'-monophosphate, cytidine-3'-monophosphate, cytidine-5'-monophosphate , Cytidine-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-xiphosphate-arabinose -glucuronic acid, uridine diphosphate-N-acetylgalactosamine, cytidine diphosphate-a-glycerine, cytidine diphosphate ribitol, cycl. AMP, cycl. GMP et al.
[0014] In einer speziellen Ausführungsform der Erfindung besteht die Gruppe der Nucleinsäurekomponenten und Nucleinsäurederivate aus Adenin, Adenosin, Cytidin, Guanin, Cytosin, Uracil, Guanosin, Uridin, Hypoxanthin, Xanthin, cycl AMP, Adenosinmonophosphat, Inosin, Harnsäure und Orotsäure. 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.
[0015] Die Gruppe der Vitamine und Mineralsalze in Bezug auf die vorliegende Erfindung umfasst alle bekannten Vitamine und Mineralsalze. Eine nicht-abschließende Liste von Vitaminen und Mineralsalzen umfasst Pyridoxol-HCI, Biotin, Thiaminchlorid, D-Panthenol Calciumpantothenat, Tocopherolsuccinat, myo-Inosit, Nicotinamid, Magnesiumsulfat, Magnesiumaspartat, Natriumdihydrogenphosphat-Monohydrat, Zinkacetat, Cobaltgluconat und Mangangluconat. 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, cobalt gluconate, and cobalt gluconate.
[0016] Die Gruppe der weiteren Zusätze in Bezug auf die vorliegende Erfindung umfasst Stoffe die die Effektivität und Wirkung der synthetischen Kamel-Organ-Extrakte verbessern, beispielsweise durch Verbesserung der Haltbarkeit, der Löslichkeit der einzelnen Bestandteile, der Pufferung oder Wirksamkeit. Die Gruppe der weiteren Zusätze umfasst u.a. Glukose, Sorbit, Mannit, Zitronensäure, Äpfelsäure, Bernsteinsäure, Benzylalkohol, Glyzerin, Ethanol, N-Methylglucamin, Natriumlactat und Natriumsuccinat. The group of further additives in relation to the present invention includes substances that improve the effectiveness and effect 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, glycerine, ethanol, N-methylglucamine, sodium lactate and sodium succinate.
[0017] In einer alternativen Ausführungsform des erfindungsgemäßen Verfahrens werden zur Herstellung der synthetischen Kamel-Organ-Extrakte a. 0,1-50 g/l, 2-10 g/l, oder 4 g/l L-Aminosäuren oder L-Aminosäurederivate, b. die sich aus 0,1-10kg, aus 1-5kg, beziehungsweise aus 2kg, Kamel-Organgewebe ergebende Peptidfraktion pro Liter synthetisches Kamel-Organ-Extrakt, c. 0,01-50 g/l, 0,1-5 g/l, oder 1 g/l Nucleinsäurekomponenten und deren Derivate, d. 0,1-1,0 g/l, 0,6-0,9 g/l, oder 0,7g/l Vitamine und 0,1-20 g/l, 1-5 g/l, oder 1,5g/l Mineralsalze, sowie e. und 0-200 g/l, 5-100 g/l, 80 g/l, 60 g/l oder 20 g/l weitere Zusätze,mit 30-40 Vol-% Wasser bei einem pH zwischen 6,0 und 7,4 vermischt (Gewicht/Volumen und Volumen/Volumen Angaben beziehen sich auf das synthetische Kamel-Organ-Extrakt Endvolumen). In an alternative embodiment of the method according to the invention, 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 0.1-10kg, from 1-5kg, or from 2kg, 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 0.7g / l vitamins and 0.1-20 g / l, 1-5 g / l, or 1.5g / l mineral salts, as well as 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% by volume of water at a pH between 6.0 and 7, 4 mixed (weight / volume and volume / volume data relate to the synthetic camel organ extract final volume).
[0018] In einer weiteren Ausführungsform des erfindungsgemäßen Verfahrens werden zur Herstellung der synthetischen Kamel-Organ-Extrakte a. als L-Aminosäuren oder L-Aminosäurederivate Glycin, Glutaminsäure je 0,3-0,4 g/l, alpha-Alanin, Asparaginsäure, Hydroxyprolin, Prolin, Serin, Lysin, Arginin je 0,2-0,4 g/l, Histidin, Ornithin, Asparagin, Valin, Tyrosin, DL-Threonin. Phenylalanin, Leucin je 0,03-0,06 g/l, Threonin, Tryptophan, Methionin β-Alanin je 0,01-0,03 g/l, Isoleucin, Cystein, Kreatinin, Hippursäure je <0,02 g/l, Urea 0,5-0,9 g/l, b. als Peptidfraktion, pro Liter synthetisches Kamel-Organ-Extrakt, die sich aus 2 kg Kamel-Organgewebe ergebende Peptidfraktion, c. als Nucleinsäurekomponenten und deren Derivate, Adenin, Adenosin, Cytidin, Guanin, Cytosin, Uracil, Guanosin, Uridin, Hypoxanthin, Xanthin, cycl.AMP, Adenosinmonophosphat je 0,01-0,03 g/l, Inosin 0,08 g/l, Harnsäure und Orotsäure je 0,02-0,03 g/l, d. als Vitamine Pyridoxol-HCI 0,5-0,7 g/l, Biotin 0,1 g/l, Thiaminchlorid, Ca-pantothenat, Tocopherolsuccinat je <0,002 g/l, myo-Inosit Nicotinsreamid je <0,03 g/l, und als Mineralsalze Magnesiumsulfat, Magnesiumaspartat und Natriumdihydrogenphosphat-Monohydrat je <0,07 g/l, Zinkacetat 0,1 g/l, Cobalt-, Mangangluconatje 0,005 g/l. e. und als weitere Zusätze Glukose, Sorbit und Mannit je 0,1-0,5 g/l, Zitronensäure 1-5 g/l, Äpfelsäure 1-2 g/l, Bernsteinsäure 5-15 g/l, Ethanol 10-50 ml/l, Benzylalkohol 1-4 ml/l., Glyzerin 0.4-1.0 g/l, N-Methylglucamin <0,5g/l, Glukosamin 1,0-2,5 g/l, Natriumlactat 1-4 g/l, Natriumsuccinat 2-15 g/l,mit 30-40 Vol-% Wasser bei einem pH zwischen 6,0 und 7,4 vermischt (Werte beziehen sich auf das Endvolumen). In a further embodiment of the process according to the invention, a. as L-amino acids or L-amino acid derivatives glycine, glutamic acid each 0.3-0.4 g / l, alpha-alanine, aspartic acid, hydroxyproline, proline, serine, lysine, arginine each 0.2-0.4 g / l, 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 <0.02 g / l each , 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 <0.002 g / l each, myo-inositol nicotine creamid <0.03 g / l each , 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., glycerine 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% by volume of water at a pH between 6.0 and 7.4 (values refer to the final volume).
[0019] In einer alternativen Ausführungsform der Erfindung wird im Verfahren zur Herstellung der synthetischen Kamel-Organ-Extrakte eine spezielle Hefezellpräparation hinzugegeben, welche zu einer weiteren Steigerung der Stoffwechselaktivität führt. Ein Beispiel einer solchen Hefezellpräparation ist H 38 („75 Years Chemistry. Re-Reading“, Band II, Seite 448-449 (ISBN 978-1-882292-34-9). In einer weiteren alternativen Ausführungsform des erfindungsgemäßen Verfahrens, wird 5-500 ml/l, 10-150 ml/l, bzw. 50 ml/l (bezogen auf das synthetische Kamel-Organ-Extrakte Endvolumen) H 38 Hefezellpräparation hinzugegeben. In einer wieder anderen Anwendungsform kann auch ein synthetischer Rinderthymus-Extrakt die zellstoffwechselaktivierenden Eigenschaften der Kamel-Organ-Extrakte verstärken. 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, FIG -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 Enhance the properties of camel organ extracts.
[0020] In einer weiteren alternativen Ausführungsform der Erfindung werden neben dem Peptidextrakt, den Aminosäuren und Nucleinsäuren und deren Derivaten, den Vitaminen, Mineralsalzen, und den weiteren Zusätzen, weitere Komponenten beigemischt, welche die zellstoffwechselaktivitätssteigernde Wirkung der Kamel-Organ-Extrakte verstärken. Komponenten welche die zellstoffwechselaktivitätssteigernde Wirkung der Kamel-Organ-Extrakte verstärken sind u.a. Kohlenhydraten und Kohlenhydratderivate, wie beispielsweise Glucose, Invertzucker, D-Mannose, D-Ribulose, L-Erythrulose-1-phosphat, D-Fructose-6-phosphat, D,L-Arabinose, N-Methylhexosamin, aliphatische Carbonsäuren mit 3 bis 6 Kohlenstoffatomen und Puffersubstanzen. 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 other additives, further components are added which increase the cell metabolism activity-increasing effect of the camel organ extracts. Components that 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, N-methylhexosamine, aliphatic carboxylic acids with 3 to 6 carbon atoms and buffer substances.
[0021] In einer weiteren Ausführungsform der Erfindung werden den synthetischen Kamelorgan-Extrakten weitere stoffwechselaktivitätssteigernde Komponenten beigemischt. Die erfindungsgemäßen synthetischen Kamel-Organ-Extrakte sind wirksame Substitute oder Ergänzungen für eine Vielzahl von Naturstoffextrakten, insbesondere für natürliche oder synthetische Säugetier-Organ- und Pflanzen-Extrakte, in der Form von Placenta-, Thymus-, Blut-, Blutserum-, Milz-, Leber-, Herzmuskel-, Elastin-, Kollagen-, Bindegewebs-, Amnionflüssigkeits-, Nabelschnur-, Quallen- und Rogenextrakte sowie Kombinationen derselben. Die erfindungsgemäßen synthetischen Kamel-Organ-Extrakte können mit solchen Naturstoffextrakten, beispielsweise natürlichen oder synthetischen Säugetier-Organ- und Pflanzen-Extrakte, kombiniert werden. In a further embodiment of the invention, the synthetic camel organ extracts are admixed with further components which increase metabolic activity. 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, 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 substance extracts, for example natural or synthetic mammalian organ and plant extracts.
[0022] Ein weiterer Aspekt der Erfindung betrifft die mit dem erfindungsgemäßen Verfahren hergestellten synthetischen Kamel-Organ-Extrakte. Die Zusammensetzung und Qualität der synthetischen Kamel-Organ-Extrakte kann mit Hilfe von im Stand der Technik üblichen analytischen Methoden validiert werden. Analytische Parameter, die so getestet werden können, umfassen pH-Wert, Trockenrückstand (5 h bei 105°C), N-Gehalt (nach Kjeldahl), Aminosäurebestimmung: qualitativ mittels Ninhydrin, mittels Dünnschichtchromatographie (TLC) und HPLC; Peptidnachweis: mittels Biuret-Reagens, Protein- Freiheit (mittels Sulfosalicylsäure); Nucleinsäurekomponenten. TLC; und Sterilitätsprüfungen nach DAB 10. 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 state of the art. Analytical parameters that can be tested in this way include pH value, 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 biuret reagent, protein-free (using sulfosalicylic acid); Nucleic acid components. TLC; and sterility tests according to DAB 10.
Tabelle 1. Qualitätsstandard von proteinfreiem, synthetischem Kamelplazenta-Extrakt (I, synthetisch)Table 1. Quality standard of protein-free, synthetic camel placenta extract (I, synthetic)
[0023] pH 6,7 - 7,5 Trockensubstanz 0,5 - 0, 8% N 0,05 - 0,08% Aminosäuren positiv Peptide (Biuret) positiv Nukleinsäuren-Komponenten positiv Hormone negativ Schwermetalle < 20 ppm Sterilität keimfrei Pyrogenität pyrogenfrei BSE BSE-freiPH 6.7-7.5 dry substance 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 pyrogen-free BSE BSE-free
[0024] Die vorstehend beschriebenen synthetischen Kamel-Organ-Extrakte können, einzeln oder in Form von Gemischen oder Kombinationen derselben mit weiteren Kollagen- oder andere Organextrakten aus dem Kamel und anderen Organismen zur Herstellung von kosmetischen Formulierungen, wie beispielsweise Cremeformulierungen. The synthetic camel organ extracts described above can, 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 cosmetic formulations, such as cream formulations.
[0025] Die synthetischen Kamel-Organ-Extrakte können außerdem einzeln oder in Form von Gemischen oder Kombinationen, unverdünnt oder verdünnt, in Form von sie enthaltenden Kapseln für die direkte orale Einnahme, beispielsweise als Nahrungsergänzungsmittel oder Nahrungsmittel-Verstärker, verwendet werden. 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 food supplements or food enhancers.
[0026] Futtermittelergänzung für Kamele durch synthetische Kamel-Organ-Extrakt-Applikation Wir fanden: a) Entsprechende Anwendungen auf Jungtiere von Kamelen, die nicht ausreichend fressen wollten: bad eater, zeigten einige Zeit nach einer solchen Behandlung Erfolg Es musste sogar bald die Gabe von derartigen Extrakten abgesetzt werden, da aus den bad eatern over eater wurden, b) Als Nahrungsergänzungsmittel eigneten sich die Kamel-Organ-Extrakte für Kamele, die rekonvaleszent waren c) Anwendung von Kamel-Organ-Extrakten als Injektionspräparate: Entsprechende Versuche konnten durch Vermittlung des Hamburger Freundes Wolfgang Seidel, und auch des ehemaligen Rektors der UFSM, Santa Maria Professor Dr. Jose Mariano da Rocha Filho, mit Kamelen ihres befreundeten Scheichs durchgeführt werden: Der Scheich erwarb einige Jahre seit positiven Rennerfolgen seiner Kamele den nach Rezeptur des Erfinders hergestellten Kamel-Thymus-Extrakt als injizierbare Lösung. 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 enough: bad eater, showed success some time after such a treatment. It even had to be given soon be discontinued from such extracts, since the bad eatern 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 possible through mediation of the Hamburg friend Wolfgang Seidel, and also of the former rector of the UFSM, Santa Maria Professor Dr. Jose Mariano da Rocha Filho, with the camels of her sheik friend: The sheik has acquired the camel thymus extract as an injectable solution, which is produced according to the inventor's recipe, for several years since his camels had positive racing successes.
[0027] Ebenso wie sich die Gärung normaler Bäckerhefe durch Zusatz der vom Verfasser entwickelten stoffwechselaktivierenden Hefe-Präparationen H 38 steigern lässt, so kann auch der Organismus von Kamelen durch Applikation stoffwechselaktivierender Kamel-Organ-Extrakte in seiner Aktivität gesteigert werden. Dies ist von Interesse für Rennkamele bzw. für Kamele in Rekonvaleszenz. 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 activity of the camel organism can also be increased by applying metabolic-activating camel organ extracts. This is of interest for racing camels or for camels in convalescence.
[0028] Die Anwendung der erfindungsgemäß hergestellten synthetischen Kamel-Organ-Extrakte, einzeln oder in Form von Gemischen oder Kombinationen derselben mit weiteren Organextrakten ist nicht auf bestimmte Lebewesen beschränkt. In einer Ausführungsform der Erfindung werden die erfindungsgemäßen synthetischen Kamel-Organ-Extrakte auf Säugetiere angewendete; beispielsweise den Menschen, das Kamel, das Pferd, das Rind, das Schaf, das Huhn oder das Schwein In einer weiteren Ausführungsform werden die erfindungsgemäßen synthetischen Kamel-Organ-Extrakte auf Mikroorganismen oder Pflanzen angewendet. 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 certain living beings. In one embodiment of the invention, the synthetic camel organ extracts according to the invention are applied to mammals; for example humans, camels, horses, cattle, sheep, chickens or pigs. In a further embodiment, the synthetic camel organ extracts according to the invention are applied to microorganisms or plants.
[0029] Herstellung von Cremeformulierungen (Wasser/Öl-Emulsionen): Seit 1965 hat der Erfinder die erfolgreiche Anwendung von mehreren proteinfreien (und enzymfreien) kosmetischen Additiven verwirklicht, wie beispielsweise OMNITHYMUS, k-PFE + CELLRYL in EVANGYL (POLA).Production of cream formulations (water / oil emulsions): Since 1965 the inventor has realized the successful use of several protein-free (and enzyme-free) cosmetic additives, such as OMNITHYMUS, k-PFE + CELLRYL in EVANGYL (POLA).
[0030] Die Begründung für den Einsatz von proteinfreien Organ-Extrakten in kosmetischen Additiven hat Erfinder in „75 Years Chemistry: Re-Reading“, Band II, Seite 320 (ISBN 978-1-882292-34-9) gegeben, ebenso dort auf Seite 524 findet sich eine Gegenüberstellung von normalen, synthetischen und in Zellkultur gewonnenen Extrakten. 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), also there on page 524 there is a comparison of normal, synthetic and cell culture extracts.
[0031] Entsprechend der nachfolgenden Zusammensetzung wurden Handcremen formuliert, denen synthetisches Extrakt I beigemischt wurde. Die Endzusammensetzung der Cremeformulierungen war wie folgt: 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:
Tabelle 2Table 2
[0032] Lösliches Lanolinderivat 1,0 acetylierte Lanolinalkohole 5,0 flüssiger Multisterol Extrakt 5,0 Vaseline 5,0 Polyvinylalkohol-Gel 0,75 10%iges NaOH 2,25 Testsubstanzen I (I, synthetisch) 0,5 äthoxylierte Fettamine 3,75 Parfumöl 0,3 Wasser, bidest auf 100 Gew% (bidest: bidestilliert) 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-distilled to 100% by weight (double-distilled: double-distilled)
[0033] Zur Herstellung dieser Cremeformulierungen wurden die Fettphasen-Bestandteile und Vaseline auf ca. 75° C erwärmt. Gleichzeitig wurde das PVA-Gel in heißem Wasser von ca. 80°C dispergiert und allmählich gelöst. Zur letzteren Dispersion wurde das ethoxylierte Fettamin mit ca. 25 EO-Einheiten und ggf. noch ein Emulgator gegeben, wonach die vorher angesetzte erwärmte Fettphase darin emulgiert wurde. Nach 5 Minuten Rühren bei der Mischungstemperatur wurde auf 60°C abgekühlt, dann mit der 10%igen Natronlauge versetzt und weiter bis auf unter 40°C gekühlt. Unter langsamem Rühren wurden dann die Formulierungen der Testlösungen (synthetisches Extrakt I) zugesetzt. Der Ansatz wurde gut homogenisiert. Die Handcreme war stabil konfektioniert und zeigte eine verbesserte Hautkonditionierung verglichen mit einem Ansatz ohne Testsubstanz-Zusatz. To produce these cream formulations, the fat phase components and petroleum jelly were heated to approx. 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 approx. 25 EO units and, if necessary, an emulsifier was added to the latter dispersion, after which the previously prepared heated fat phase was emulsified in it. After stirring for 5 minutes at the mixture temperature, the mixture was cooled to 60.degree. C., then 10% sodium hydroxide solution was added and the mixture was cooled further to below 40.degree. The formulations of the test solutions (synthetic extract I) were then added with slow stirring. The batch was homogenized well. The hand cream was packaged in a stable manner and showed improved skin conditioning compared with a batch without the addition of test substance.
Kamel-Bindegewebs-Komponenten (Kamel-Kollagene)Camel connective tissue components (camel collagens)
Herstellung:Manufacturing:
[0034] Kamelhaut wurde, nach Entfernen von Blut, Fleisch und Fett, zerkleinert und anschließend je nach Ziel der Extraktion mit Neutralsalzen oder Säuren unterzogen, in gefriergetrocknetem Zustand oder als Lösung (Sorbinsäure-Zusatz zur Konservierung) aufbewahrt (siehe Dtsch.Apotheker-Ztg.117, 1557-62 (1977)). Vergleichbare Verfahren sind im Stand der Technik für die Gewinnung anderer Säugetier-Kollagenen beschrieben. Kamel-Kollagen: N 18% +- 0,3 Hydroxyprolin-Gehalt: 14-15%. Camel skin was, after removing blood, meat and fat, crushed and then, depending on the objective, subjected to extraction with neutral salts or acids, stored in a freeze-dried state or as a solution (sorbic acid addition for preservation) (see Dtsch.Apotheker-Ztg .117: 1557-62 (1977)). Similar methods are described in the prior art for obtaining other mammalian collagens. Camel collagen: N 18% + - 0.3 Hydroxyproline content: 14-15%.
[0035] Gemäß einer alternativen Ausführungsform der Erfindung werden die durch das erfindungsgemäße Verfahren hergestellten synthetischen Kamel-Organ-Extrakte mit einer oder mehreren Kamel-Bindegewebs-Komponenten vermischt. Beispiele solcher Bindegewebs-Komponenten sind Kollagen-Typen, Elastine, Fibronectine, Kreatine und Hyaluronsäure. 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.
BeispieleExamples
Bespiel 1Example 1
[0036] Herstellung von synthetischem Kamel-Plazenta-Extrakt (I, synthetisch) als 1 Liter Ansatz Die folgenden Komponenten, berechnet auf ein Endvolumen von 1 I, wurden unter Rühren und sterilen Bedingungen in einem Volumen von bidest. H20 gelöst, welches 3/10 bis 4/10 des Endvolumens entspricht. Der pH-Wert wurde zwischen 6,0 und 7,4 gehalten: L-Aminosäuren und Derivate: Glycin, Glutaminsäure je 0,3-0,4g, a-Alanin, Asparaginsäure, Hydroxyprolin, Prolin, Serin, Lysin, Arginin je 0,2-0,4g, Histidin, Ornithin, Asparagin, Valin, Tyrosin, DL-Threonin. Phenylalanin, Leucin je 0,03-0,06g, Threonin, Tryptophan, Methionin β-Alanin je 0,01-0,03g, Isoleucin, Cystein, Kreatinin, Hippursäure je <0,02g, Urea 0,5-0,9g. Peptidfraktion aus Kamel-Plazentadrüsen: 10kg aufgetauter, blutfrei gewaschener und in einer Zahnkolloidmühle (bis zu Brei 0,3mm) zerkleinerter Drüsen wurden in 4 L Ether + 300 ml Ethanol im Kühlraum unter -10°C zehn Tage aufbewahrt, dann in einer explosionssicheren Trommelzentrifuge getrennt. Unter Änderung der osmotischen Bedingungen des Zentrifugates (+150gNaCl) und gleichzeitigem Erwärmen auf 60°C spalteten die im Zentrifugat enthaltenen Proteine Peptide ab; dann wurde Luft durchgeleitet, und zwar bei pH 7,5 zur Entfernung des Ethers, und - nach Änderung des pHs auf 3,4 mit Bernsteinsäure - zur Entfernung restlicher Proteine [ausreichend lange Luft oder Sauerstoff durchleiten: Prüfung mit Sulfosalizylsäure]. Nach Millipore-Filtration (Porenweite 0,22 Mikrometer) wurde die im Beispiel erforderliche Peptidfraktion erhalten (Durchfluss), wobei die aus 10kg Kamel-Plazentadrüsen erhaltene Menge für 5 L synthetischen I-Extrakt ausreicht, d.h. nur 1/5 im Beispiel eingesetzt wird. Nucleinsäurekomponenten und Derivate: Adenin, Adenosin, Cytidin, Guanin, Cytosin, Uracil, Guanosin, Uridin, Hypoxanthin, Xanthin, cycl.AMP, Adenosinmonophosphat je 0,01-0,03g, Inosin 0,08g, Harnsäure, Orotsäure 0,02-0,03g. Vitamine: Pyridoxol-HCI 0,5-0,7g, Biotin 0,1g, Thiaminchlorid, Ca-pantothenat, Tocopherolsuccinat je <0,002g, myo-Inosit Nicotinsreamid je <0,03g. Mineralsalze: Mg-sulfat, Mg-aspartat, NaH2PO4-H2O je <0,07g, Zn-acetat: 0,1g, Co-, Mn-gluconat je 0,005g. Weitere Zusätze: Glukose, Sorbit, Mannit je 0,1-0,5g, Zitronensäure 1-5g, Äpfelsäure 1-2g, Bernsteinsäure 5-15g, Ethanol 10-50ml, Benzylalkohol 1-4ml., Glyzerin 0.4-1.0g/l, N-Methylglucamin <0,5g, Nalactat 1-4g, Na-succinat 2-15g, Natriumchlorid 1-10g, Konservierung ggf ohne.Production of synthetic camel placenta extract (I, synthetic) as a 1 liter batch The following components, calculated to a final volume of 1 l, were in a volume of double distilled with stirring and under sterile conditions. H20 dissolved, which corresponds to 3/10 to 4/10 of the final volume. The pH value was kept between 6.0 and 7.4: L-amino acids and derivatives: glycine, glutamic acid each 0.3-0.4g, a-alanine, aspartic acid, hydroxyproline, proline, serine, lysine, arginine each 0 , 2-0.4g, histidine, ornithine, asparagine, valine, tyrosine, DL-threonine. Phenylalanine, leucine 0.03-0.06g each, threonine, tryptophan, methionine β-alanine 0.01-0.03g each, isoleucine, cysteine, creatinine, hippuric acid <0.02g each, urea 0.5-0.9g . Peptide fraction from camel's placental glands: 10kg of thawed, blood-free washed glands comminuted in a tooth colloid mill (up to 0.3 mm pulp) were stored in 4 L ether + 300 ml ethanol in a cold room below -10 ° C for ten days, then in an explosion-proof drum centrifuge Cut. By changing the osmotic conditions of the centrifugate (+ 150gNaCl) and simultaneous 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 [pass air or oxygen through for a long enough time: test with sulfosalicylic acid]. After Millipore filtration (pore size 0.22 micrometers), the peptide fraction required in the example was obtained (flow-through), 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 0.01-0.03g, inosine 0.08g, uric acid, orotic acid 0.02- 0.03g. Vitamins: Pyridoxol-HCI 0.5-0.7g, biotin 0.1g, thiamine chloride, calcium pantothenate, tocopherol succinate <0.002g each, myo-inositol nicotine creamid <0.03g each. Mineral salts: Mg sulfate, Mg aspartate, NaH2PO4-H2O each <0.07g, Zn acetate: 0.1g, Co-, Mn-gluconate each 0.005g. Further additives: glucose, sorbitol, mannitol each 0.1-0.5g, citric acid 1-5g, malic acid 1-2g, succinic acid 5-15g, ethanol 10-50ml, benzyl alcohol 1-4ml., Glycerine 0.4-1.0g / l , N-methylglucamine <0.5g, nalactate 1-4g, Na-succinate 2-15g, sodium chloride 1-10g, preservation if necessary without.
[0037] Bei der Herstellung der Lösung ist zu beachten, dass manche Komponenten in NaOH oder HCl vorgelöst und neutralisiert werden müssen, z.B. die Aminosäuren Glu, Asp, Val, Tyr, Phe, Isoleu, Leu in 2 N NaOH, Xanthin in 3 N NaOH, Guanin in 3N HCl. When preparing the solution, it should be noted that some components must be pre-dissolved and neutralized in NaOH or HCl, for example the amino acids Glu, Asp, Val, Tyr, Phe, Isoleu, Leu in 2N NaOH, xanthine in 3N NaOH, guanine in 3N HCl.
[0038] Nach Auffüllen mit bidest. Wasser auf 11 Endvolumen wurde nochmals der pH eingestellt und sterilfilriert. After filling up with redist. Water to 11 final volumes, the pH was adjusted again and sterile-filtered.
Beispiel 2Example 2
[0039] Synthetischer Extrakt I plus H 38 (später Y 20): Das Herstellungsverfahren wurde durchführen, wie für Beispiel 1 angegeben. Vor Auffüllung auf 1 I wurden 50 ml H 38 (Y 20), eine spezielle Hefezellpräparation, hinzugegeben und mit bidest. Wasser auf 11 aufgefülltSynthetic extract I plus H 38 (later Y 20): The production process was carried out as indicated for Example 1. Before making up to 1 l, 50 ml of H 38 (Y 20), a special yeast cell preparation, were added and mixed with redist. Water topped up to 11
[0040] Der gemessene Atmungssteigerungsfaktor betrug 2,6. The measured respiratory increase factor was 2.6.
Beispiel 3Example 3
[0041] PADBERG Methode: Im Padberg-Test wird die Absorption von Methylenblau in die Haut bewertet, wobei die Absorptionsmenge mit der Trockenheit der Haut in Verbindung steht. Dies beruht auf der Beobachtung, dass die Absorption von auf die Haut aufgetragenem Methylenblau proportional zur Hauttrockenheit ist; sodass je höher die Rauigkeit desto mehr Methylenblau absorbiert wird.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 the dryness of the skin; so that the higher the roughness, the more methylene blue is absorbed.
[0042] Für die Durchführung des Padberg-Tests werden für gewöhnlich 5-15 Testpersonen im Alter von 35-65 Jahren herangezogen. Die Testpersonen werden angewiesen 3 Tage vor Beginn sowie während des Tests keine Kosmetika auf den Hautbereichen zu verwenden die für den Test untersucht werden. Pro Testperson werden jeweils 6 Testfelder auf beiden Unterarm-Innenseiten markiert, wobei eines der Testfelder unbehandelt bleibt. Zunächst wird für jedes Testfeld ein Padberg-Test durchgeführt um den Leerwert zu bestimmen. Danach wird die zu testende Substanz von den Testpersonen zweimal täglich, morgens und abends, über 14 Tage hinweg auf die Teststellen aufgetragen. Vier Stunden nach der letzten Auftragung wird ein weiterer Padberg-Test durchgeführt. 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 that are examined for the test 3 days before the start of the test and during the test. For each test person, 6 test fields are marked on the inner sides of the forearm, whereby one of the test fields remains untreated. First of all, a Padberg test is carried out for each test field to determine the blank value. The test subjects then apply the substance to be tested to the test sites twice a day, in the morning and in the evening, over a period of 14 days. Another Padberg test is carried out four hours after the last application.
[0043] Der Padberg-Test wird durchgeführt wie zum Beispiel im Journ. Soc. Cosmetic Chemicals 20, 719-728, [1969] beschrieben. The Padberg test is carried out as for example in Journ. Soc. Cosmetic Chemicals 20, 719-728, [1969].
Ergebnisse der PADBERG Tests: Tabelle 3Results of the PADBERG tests: Table 3
[0044] In der folgenden Tabelle 3 sind die Photometer-Werte für eine Cremezusammensetzung mit Zusatz von synthetischem Extrakt I oder ohne (Placebo-Creme), ausgedrückt in Prozent des Wertes bei behandelter Haut und bezogen auf den Ausgangswert, zusammengefasst. In der Tabelle 3 sind auch die berechneten Mittelwerte angegeben. In Table 3 below, the photometer values for a cream composition with or without the addition of synthetic extract I (placebo cream), expressed as a percentage of the value for treated skin and based on the initial value, are summarized. Table 3 also shows the calculated mean values.
[0045] Die Ergebnisse zeigen, dass mit den Cremeformulierungen mit Zusatz von synthetischem Extrakt I eine Glättung der Haut erzielbar ist. Entsprechendes hat sich auch bei der Verwendung eines synthetischen Thymus-Extraktes als Zusatz gezeigt. The results show that the cream formulations with the addition of synthetic extract I can be used to smooth the skin. The same has also been shown when a synthetic thymus extract is used as an additive.
[0046] Tabelle 3: Rauhigkeitstest nach der PADBERG-Methode mit Cremeformulierungen (Wasser/Öl-Emulsionen) mit und ohne Zusatz von synthetischem Kamel-Plazenta-Extrakt (synthetisches Extrakt I) (Anwendungsdauer 14 Tage). 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 Mittelwerte 85,6 56,4Table 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). 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 mean values 85.6 56.4
Vergleichsbeispiel 4Comparative example 4
WARBURG Methode - VersuchWARBURG method - trial
[0047] In einer WARBURG-Apparatur wurde mit Hilfe manometrischer Messungen die Stoffwechselaktivität von Produkten, und zwar im Falle des Einsatzes von Leberhomogenat von Ratten bzw. Meerschweinchen die Atmungssteigerung - durch Messung der O2-Aufnahme bestimmt. Entsprechend dem Füllplan wurden die Seitenbirnen der Gefäße mit Testlösung oder Wasser beschickt. Es lässt sich der Reaktionsverlauf mit und ohne Produkt-Zusatz vergleichen. Die Gefäße wurden mit den Manometern verbunden. Die Manometer wurden in den Thermostaten eingehängt und bis zur Solltemperatur erwärmt. Dann wurde durch Kippen Testlösung bzw. Wasser aus dem Seitengefäß in das Hauptgefäß eingebracht. Dies ist der eigentliche Reaktionsbeginn. Die einzelnen Ablesungen erfolgten in Abständen von 10 Min, die Ergebnisse werden in den Messplan eingetragen. Der Warburg-Versuch geht über 90 Min. Die Ergebnisse liefern die Faktoren für die Steigerung der Stoffwechselaktivität. In a WARBURG apparatus, the metabolic activity of products was determined with the help of manometric measurements, and in the case of the use of liver homogenate from rats or guinea pigs, the increase in breathing - determined by measuring the O2 uptake. According to the filling plan, the side bulbs of the vessels were filled with test solution or water. The course of the reaction can be compared with and without the addition of product. The vessels were connected to the manometers. The pressure gauges were hung in the thermostat and heated up to the target temperature. Then test solution or water was introduced from the side vessel 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 experiment lasts 90 minutes. The results provide the factors for increasing metabolic activity.
MessplanMeasurement plan
[0048] Beispiel: Roggen Extrakt mit Faktor 1,83. Kontrolle: 1,0 (Pre-Inkubation 1 h bei 37°C): Example: rye extract with a factor of 1.83. Control: 1.0 (pre-incubation 1 h at 37 ° C):
Tabelle 4Table 4
[0049] [0049]
Tabelle 5 Table 5
[0050] Roggen Extrakt 1,83 Kontrolle 1,0 Schweineplazenta-Extrakt 1,85 Rinderplazenta-Extrakt 1,8Rye extract 1.83 control 1.0 pig placenta extract 1.85 bovine placenta extract 1.8
Beispiel 5Example 5
[0051] In analoger Weise zu Vergleichsbeispiel 4 wurden Atmungssteigerungsfaktoren gemessen für synthetisches Extrakt I, synthetisches Extrakt II, synthetischen Kamelleber- Extrakt und für Kamel-NGF (Nerve Growth Promoting Factor). In a manner analogous 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).
Tabelle 6Table 6
[0052] synthetisches Extrakt I 2,3 synthetisches Extrakt II 2,2 - 2,5 synthetischen Kamelleber-Extrakt 2,3 - 2,4 Kamel-NGF 2,4Synthetic extract I 2.3 synthetic extract II 2.2-2.5 synthetic camel liver extract 2.3-2.4 camel NGF 2.4
[0053] Während der BSE-Krise konnten Kamelorgan-Extrakte beispielsweise die unerwünschten Rinderplazenta-Extrakte ersetzen: Länder, in denen Kamele aufwachsen, waren unter Garantie BSE-frei. Der oben aufgeführte Wert für Kamel-NGF ist von Bedeutung: In klinischen Versuchen gelang es in Japan, mit Kamel-NGF bei der Behandlung von facial paralsis positive Ergebnisse zu erzielen. Über frühere Ergebnisse mit NGF-Präparaten anderer Tiere ist in Verfassers „Re-Reading“, Band II, Seite 295: ISBN 978-1-882292-34-9 berichtet worden. Die Gewinnung von Kamel-NGF erfolgte nach der dort für andere Säugetiere beschriebenen Methode: Analyse-Daten zu Ve) jener Vorschrift für Kamel-NGF: Ausb.: 1,8g pro kg KamelSpeicheldrüse, mit einer biologischen Aktivität in BU von 0,010- 0,019 µg/g. Durchführung der biologischen Identifizierung und Bewertung von Kamel-NGF nach Angaben, wie sie Montalcini, Cancer Research 14, 49ff (1954) für die Gewinnung und die Charakterisierung von Mäuse-NGF gemacht hat. Mit der Gewinnung von Kamel-NGF aus einer Speicheldrüse des Kamels wurden gleichzeitig Literaturangaben widerlegt, dass es in den Speicheldrüsen von Großtieren keine NGF-Faktoren gibt (Zusammenarbeit mit Prof. Dr. T. Yamamoto). During the BSE crisis, for example, camel organ extracts were able to replace the undesirable bovine placenta extracts: countries in which camels grow up were guaranteed to be BSE-free. The above value for camel NGF is significant: In clinical trials in Japan, camel NGF has shown positive results in the treatment of facial paralsis. Earlier 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. The extraction of camel NGF was carried out according to the method described there for other mammals: Analysis data for Ve) that regulation for camel NGF: Yield: 1.8 g per kg of camel's salivary gland, with a biological activity in BU of 0.010-0.019 µg /G. Carrying out the biological identification and evaluation of camel NGF according to information such as those made by Montalcini, Cancer Research 14, 49ff (1954) for the extraction and characterization of mouse NGF. With the extraction of camel NGF from a camel's salivary gland, literature references were simultaneously refuted that there are no NGF factors in the salivary glands of large animals (collaboration with Prof. Dr. T. Yamamoto).
[0054] Durch Kombination, z.B. mit H 38 (später Y 20), einer speziellen Hefezellpräparation (75 Years Chemistry- Re-Reading, Band II (ISBN 978-1-828292), Seiten 448-449 und ref [11,14]), lässt sich die Aktivität dieses Extraktes weiter steigern. By combination, for example 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 extract can be further increased.
Beispiel 6Example 6
[0055] Im Folgenden sind Ergebnisse von Aktivitätstests für synthetisches Extrakt I und zum Vergleich Schweine-Plazenta-Extrakt aufgeführt sowie Hinweise auf die angewandten Arbeitsmethoden: The following are the results of activity tests for synthetic extract I and, for comparison, pig placenta extract, as well as information on the working methods used:
Tabelle 7Table 7
[0056] PADBERG-Test (wie oben) 56,4 (85,6) 64,5 (88,9) Metamorphosebeginn-Kürzung Xenopus<1> 5-8 Tage 3-4 Tage Wundheilung (Hautspannung)<2> 240 235 <1>Beschreibung der Methodik in „Re-Reading“, Part IV, p 448-456: IBSN 978-1-882292-36-3 <2>Methodik in „Cosmetics and Toiletries“ 92, 25-27 (1977)PADBERG test (as above) 56.4 (85.6) 64.5 (88.9) metamorphosis onset shortening Xenopus <1> 5-8 days 3-4 days wound healing (skin tension) <2> 240 235 <1> Description of the methodology in "Re-Reading", Part IV, p 448-456: IBSN 978-1-882292-36-3 <2> Methodology in "Cosmetics and Toiletries" 92, 25-27 (1977)
[0057] Beginn der Metamorphose beim Kamel-Plazenta synthetisch I 5-8 Tage vor Kontrolle, wohingegen bei Schweine-Plazenta synthetisch I 3-4 Tage vor Kontrolle (vgl. Tabelle 7). Beginning of metamorphosis in the camel placenta synthetic I 5-8 days before the control, whereas in the pig placenta synthetic I 3-4 days before the control (see Table 7).
[0058] Angaben über die Quellen genetischer Ressourcen gemäss Art. 49a PatG Kamel-Organ-Extrakt nicht bekannt Hefezellpräparate nicht bekannt Säugetier-Organ-Extrakt nicht bekanntInformation on the sources of genetic resources according to Art. 49a PatG Camel organ extract not known Yeast cell preparations not known Mammalian organ extract not known
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DE112016007409.3T DE112016007409A5 (en) | 2016-11-04 | 2016-11-29 | SYNTHETIC CAMEL ORGAN EXTRACTS, PROCESS FOR THEIR PREPARATION AND THEIR USE |
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