CH713107A2 - Synthetic camel organ extracts, process for their preparation and their use. - Google Patents
Synthetic camel organ extracts, process for their preparation and their use. Download PDFInfo
- Publication number
- CH713107A2 CH713107A2 CH01466/16A CH14662016A CH713107A2 CH 713107 A2 CH713107 A2 CH 713107A2 CH 01466/16 A CH01466/16 A CH 01466/16A CH 14662016 A CH14662016 A CH 14662016A CH 713107 A2 CH713107 A2 CH 713107A2
- Authority
- CH
- Switzerland
- Prior art keywords
- camel
- acid
- synthetic
- organ
- organ extracts
- 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 pharmazeutischen, kosmetischen, diätetischen und sonstigen Zusammensetzungen.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.
Description
Beschreibung [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.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.
[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 Schweineund Rinderzucht). Zur Familie der Kamele gehören: Kamel (300-950 kg) mit zwei Höckern (Asien), Dromedar (300-500 kg) 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) 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.
[0003] Seit 1947 hat der Erfinder das Kamel in seine Forschungen über tierische Organextrakte von Schwein, Rind, Pferd miteingeschlossen, 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 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.
[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 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.
[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 Bestandteil von pharmazeutischen Zusammensetzungen (z.B. für die Stimulierung der Wundheilung), 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, 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.
Zusammenfassung der Erfindung [0006] Zur Lösung der vorliegenden Aufgabe wird (1) ein Verfahren zur Herstellung von synthetischen Kamel-Organ-Extrakten bereitgestellt, umfassend das MischenSUMMARY OF THE INVENTION To achieve the present object, (1) a method for producing synthetic camel organ extracts is provided, which comprises mixing
a. von einer oder mehreren L-Aminosäuren und deren Derivaten,a. of one or more L-amino acids and their derivatives,
b. einer Peptidfraktion aus einem Kamel-Organ-Extrakt,b. a peptide fraction from a camel organ extract,
c. von einer oder mehreren Nucleinsäurekomponenten und deren Derivaten,c. of one or more nucleic acid components and their derivatives,
d. von einem oder mehreren Vitaminen und Mineralsalzen, c. und weiteren Zusätzen, mit 30-40 Vol-% Wasser bei einem pH zwischen 6,0 und 7,4.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.
[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.(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.
[0008] (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.(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.
[0009] (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 durchgeleitet wird.(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.
[0010] (5) Verfahren gemäss einem der Punkte 1-4, wobei die Peptidfraktion aus einem Kamel-Planzenta-Extrakt, KamelThymus-Extrakt oder einem Kamel-Leber-Extrakt erhalten wird.(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.
[0011] (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.(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.
[0012] (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-lnosit, Nicotina2 mid, Magnesiumsulfat, Magnesiumaspartat, Natriumdihydrogenphosphat-Monohydrat, Zinkacetat, Cobaltgluconat und Mangangluconat.(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.
[0013] (8) Verfahren gemäss einem der Punkte 1-7, wobei die weiteren Zusätze auszuwählen sind aus der Gruppe umfassend Glukose, Sorbit, Mannit, Zitronensäure, Apfelsäure, Bernsteinsäure, Benzylalkohol, Glyzerin, Ethanol, N-Methylglucamin, Glukosamin, Natriumlactat und Natriumsuccinat.(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.
[0014] (9) Verfahren gemäss einem der Punkte 1 -8 wobei zur Herstellung der synthetischen Kamel-Organ-Extrakte(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, oder 4 g/l L-Aminosäuren oder L-Aminosäurederivate,a. 0.1-50 g / l, 2-10 g / l, or 4 g / l L-amino acids or L-amino acid derivatives,
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,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, oder 1,0 g/l Nucleinsäurekomponenten und deren Derivate,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, oder0,7g/l Vitamine und 0,1-20 g/1,1-5 g/l, oder 1,5g/l Mineralsalze, sowied. 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. 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).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).
[0015] (10) Verfahren gemäss einem der Punkte 1-9, wobei zur Herstellung der synthetischen Kamel-Organ-Extrakte(10) Method according to one of items 1-9, wherein for the production of the synthetic camel organ extracts
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,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. als Peptidfraktion, pro Liter synthetisches Kamel-Organ-Extrakt, die sich aus 2 kg Kamel-Organgewebe ergebende Peptidfraktion,b. as a peptide fraction, per liter of synthetic camel organ extract, the peptide fraction resulting from 2 kg of camel organ tissue,
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,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. als Vitamine Pyridoxol-HCI 0,5-0,7 g/l, Biotin 0,1 g/l, Thiaminchlorid, Ca-pantothenat, Tocopherolsuecinat je <0,002 g/l, myo-lnosit Nicotinsreamid je <0,03 g/l, und als Mineralsalze Magnesiumsulfat, Magnesiumaspartat und Natriumdihydrogen-phosphat-Monohydrat je <0,07 g/l, Zinkacetat 0,1 g/l, Cobalt-, Mangangluconat je 0,005 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. und als weitere Zusätze Glukose, Sorbit und Mannit je 0,1-0,5 g/l, Zitronensäure 1-5 g/l, Apfelsäure 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). [0016] (11) Verfahren gemäss einem der Punkte 1-10, wobei ausserdem eine Hefezellpräparation beigemischt wird.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.
[0017] (12) Verfahren gemäss einem der Punkte 1-11, wobei weitere Komponenten beigemischt werden, welche die zellstoffwechselaktivitätssteigernde Wirkung der Kamel-Organ-Extrakte verstärken.(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.
[0018] (13) Verfahren gemäss einem der Punkte 1-12, wobei den synthetischen Kamelorgan-Extrakten weitere stoffwechselaktivitätssteigernde Komponenten beigemischt werden.(13) Method according to one of the items 1-12, wherein the synthetic camel organ extracts are admixed with further metabolic activity-increasing components.
[0019] (14) Verfahren gemäss einem der Punkte 1-13, wobei den synthetischen Kamel-Organ-Extrakten weitere natürliche oder synthetische Säugetier-Organ-Extrakte beigemischt werden.(14) Method according to one of items 1-13, wherein the synthetic camel organ extracts further natural or synthetic mammalian organ extracts are admixed.
[0020] (15) Verfahren gemäss einem der Punkte 1-14, wobei den synthetischen Kamel-Organ-Extrakten weitere natürliche oder synthetische Pflanzen-Extrakte beigemischt werden.(15) Method according to one of the items 1-14, wherein the synthetic camel organ extracts further natural or synthetic plant extracts are added.
[0021] (16) Synthetische Kamel-Organ-Extrakte und -Extraktgemische, wie sie nach dem Verfahren nach einem der Punkte 1-15 erhältlich sind.(16) Synthetic camel organ extracts and extract mixtures, such as those obtainable by the process according to one of items 1-15.
[0022] (17) Pharmazeutische Zusammensetzung, umfassend synthetische Kamel-Organ-Extrakte und -Extraktgemische, wie sie nach dem Verfahren nach einem der Punkte 1 bis 15 erhältlich sind, für die topische, subkutane, intravenöse oder intramuskuläre Anwendung zum Zwecke der äusseren oder inneren Wundheilung, zur Behandlung von Arteriosklerose oder von Strahlungsschäden.(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.
[0023] (18) Verwendung der synthetischen Kamel-Organ-Extrakte und Extraktgemische nach einem der Punkte 1 bis 15 zur Herstellung einer medizinischen Zusammensetzung für die topische, subkutane, intravenöse oder intramuskuläre Anwendung zum Zwecke der äusseren oder inneren Wundheilung, zur Behandlung von Arteriosklerose oder von Strahlungsschäden.(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.
[0024] (19) Verwendung der synthetischen Kamel-Organ-Extrakte und Extraktgemische, wie sie nach dem Verfahren nach einem der Punkte 1 bis 15 erhältlich sind, als kosmetische Additive.(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.
[0025] (20) Verwendung der synthetischen Kamel-Organ-Extrakte und Extraktgemische, wie sie nach dem Verfahren nach einem der Punkte 1 bis 15 erhältlich sind, als Nahrungsmittel-Verstärker.(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.
[0026] (21) Verfahren gemäss einem der Punkte 1-15, wobei die synthetischen Kamel-Organ-Extrakte mit einer oder mehreren Kamel-Bindegewebs-Komponenten vermischt werden.(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.
[0027] (22) Verfahren gemäss Punkt 21, wobei die Kamel-Bindegewebs-Komponenten auszuwählen sind aus der Gruppe umfassend Kollagen-Typen, Elastine, Fibronektine, Kreatine und Hyaluronsäure.(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.
Detaillierte Beschreibung der Erfindung [0028] 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.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.
[0029] 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, Cyste in säure, 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, O-Acetyl-L-serin, N-Acetyl-L-threonin, N-Acetyl-L-tryptophan, N-Acetyl-L-valin, L-allo-lsoleucin, L-alloThreonin, N-Benzoyl-L-arginin, N-Benzoyl-L-histidin, N-Benzoyl-L-lysin, N-Benzoyl-L-methionin, N-Benzoyl-L-ornithin, NBenzoyl-L-phenylalanin, N-Benzoyl-L-tryptophan, N-Benzoyl-L-valin, S-Benzoyl-L-cystein, O-Benzoyl-L-serin, O-BenzoylL-tyrosin, L-Carnosin (ß-Alanyl-L-histidin), Ν,Ο-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 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.
[0030] In einer alternativen Ausführungsform der Erfindung besteht die Gruppe von geeigneten L-Aminosäuren und LAminosäurederivaten 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 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] 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 um) wird die erforderliche Peptidfraktion (Durchfluss) erhalten.[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.
[0032] 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 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.
[0033] 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-ß-D-Ribofuranosyl-6-methylanninopurin, 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, lnosin-3'-phosphorsäure, lnosin-5'-phosphorsäure, lnosin-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-ö’-monophosphat, Cytidin4The 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'-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, Cytidindiphosphat-ribitol, cycl. AMP, cycl. GMP u.a.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
[0034] 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.
[0035] 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-lnosit, 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 and manganese gluconate, cobalt acetate.
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, Apfelsäure, Bernsteinsäure, Benzylalkohol, Glyzerin, Ethanol, N-Methylglucamin, Natriumlactat und Natriumsuccinat.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.
[0036] In einer alternativen Ausführungsform des erfindungsgemässen Verfahrens werden zur Herstellung der synthetischen Kamel-Organ-ExtrakteIn 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, oder 4 g/l L-Aminosäuren oder L-Aminosäurederivate,a. 0.1-50 g / l, 2-10 g / l, or 4 g / l L-amino acids or L-amino acid derivatives,
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,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, oder 1 g/l Nucleinsäurekomponenten und deren Derivate,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, oder0,7g/l Vitamine und 0,1-20 g/l, 1-5 g/l, oder 1,5g/l Mineralsalze, sowied. 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. 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).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 einer weiteren Ausführungsform des erfindungsgemässen Verfahrens werden zur Herstellung der synthetischen Kamel-Organ-Extrakte[0037] In a further embodiment of the method according to the invention, the synthetic camel organ extracts are used to produce
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,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. als Peptidfraktion, pro Liter synthetisches Kamel-Organ-Extrakt, die sich aus 2 kg Kamel-Organgewebe ergebende Peptidfraktion,b. as a peptide fraction, per liter of synthetic camel organ extract, the peptide fraction resulting from 2 kg of camel organ tissue,
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,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. 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-lnosit Nicotinsreamid je <0,03 g/l, und als Mineralsalze Magnesiumsulfat, Magnesiumaspartat und Natriumdihydrogen-phosphat-Monohydrat je <0,07 g/l, Zinkacetat 0,1 g/l, Cobalt-, Mangangluconat je 0,005 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. und als weitere Zusätze Glukose, Sorbit und Mannit je 0,1-0,5 g/l, Zitronensäure 1-5 g/l, Apfelsäure 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).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).
[0038] In einer alternativen Ausführungsform der Erfindung wird im Verfahren zur Herstellung der synthetischen KamelOrgan-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 mi/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, 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.
[0039] 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 und die 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 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.
[0040] 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, 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.
[0041] 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 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.
Tabelle 1: Qualitätsstandard von proteinfreiem, synthetischem Kamelplazenta-Extrakt (I, synthetisch) [0042]Table 1: Quality standard of protein-free, synthetic camel placenta extract (I, synthetic) [0042]
[0043] Gemäss einem weiteren Aspekt betrifft die Erfindung die Verwendung der vorstehend beschriebenen synthetischen Kamel-Organ-Extrakte, einzeln oder in Form von Gemischen oder Kombinationen derselben mit weiteren Kollagen- oder andere Organextrakten aus dem Kamel und anderen Organismen zur Herstellung medizinischer und pharmazeutischer Zusammensetzungen, unter anderem für die Stärkung des Immunsystems, für die Aktivierung des Zellstoffwechsels oder für die Behandlung gastroenterologischer Erkrankungen, insbesondere Ulcera, und für die topische, subkutane, intravenöse oder intramuskuläre Anwendung zum Zwecke der äusseren oder inneren Wundheilung, zur Behandlung von Arteriosklerose oder von Strahlungsschäden. Eine weitere erfindungsgemässe Verwendung der synthetischen Kamel-OrganExtrakte besteht in der Herstellung von kosmetischen Formulierungen, wie beispielsweise Cremeformulierungen.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.
[0044] 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 a dietary supplement or food enhancer.
[0045] 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 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.
[0046] 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 stoff6 wechselaktivierender 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 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.
[0047] 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 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.
Herstellung von Cremeformulierungen (Wasser/Öl-Emulsionen):Production of cream formulations (water / oil emulsions):
[0048] 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).Since 1965, the inventor has successfully implemented several protein-free (and enzyme-free) cosmetic additives, such as OMNITHYMUS, k-PFE + CELLRYL in EVANGYL (POLA).
[0049] 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), as well as there on page 524 there is a comparison of normal, synthetic and cell culture extracts.
[0050] 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 2 [0051]Table 2
[0052] 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 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.
Kamel-Bindegewebs-Komponenten (Kamel-Kollagene) [0053] Herstellung:Camel connective tissue components (camel collagens) [0053] Production:
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.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.
Kamel-Kollagen: N 18% +-0,3 Hydroxyprolin-Gehalt: 14-15%.Camel collagen: N 18% + -0.3 hydroxyproline content: 14-15%.
[0054] 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.
Beispiele [0055] Beispiel 1Examples Example 1
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: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:
[0056] L-Aminosäuren und Derivate:L-amino acids and derivatives:
Glycin, Glutaminsäure je 0,3-0,4 g, a-Alanin, Asparaginsäure, Hydroxyprolin, Prolin, Serin, Lysin, Arginin je 0,2-0,4 g, Histidin, Ornithin, Asparagin, Valin, Tyrosin, DL-Threonin. Phenylalanin, Leucin je 0,03-0,06 g, Threonin, Tryptophan, Methionin β-Alanin je 0,01 -0,03 g, Isoleucin, Cystein, Kreatinin, Hippursäure je <0,02 g, Urea 0,5-0,9 g.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.
[0057] Peptidfraktion aus Kamel-Plazentadrüsen:Peptide fraction from camel placenta glands:
kg 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 (+150gNaCI) 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 Sulfosalizylsäurej. Nach Millipore-Filtration (Porenweite 0,22 Mikrometer) wurde die im Beispiel erforderliche Peptidfraktion erhalten (Durchfluss), wobei die aus 10 kg Kamel-Plazentadrüsen erhaltene Menge für 5 L synthetischen l-Extrakt ausreicht, d.h. nur 1/5 im Beispiel eingesetzt wird. [0058] Nucleinsäurekomponenten und Derivate: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 [pass 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:
Adenin, Adenosin, Cytidin, Guanin, Cytosin, Uracil, Guanosin, Uridin, Hypoxanthin, Xanthin, cycl.AMP, Adenosinmonophosphat je 0,01-0,03 g, Inosin 0,08 g, Harnsäure, Orotsäure 0,02-0,03 g.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.
[0059] Vitamine:Vitamins:
Pyridoxol-HCI 0,5-0,7 g, Biotin 0,1 g, Thiaminchlorid, Ca-pantothenat, Tocopherolsuccinat je <0,002 g, myo-lnosit Nicotinsreamid je <0,03 g.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.
[0060] Mineralsalze:Mineral Salts:
Mg-sulfat, Mg-aspartat, NaH2P04-H20 je <0,07 g, Zn-acetat: 0,1 g, Co-, Mn-gluconat je 0,005 g.Mg sulfate, Mg aspartate, NaH2P04-H20 each <0.07 g, Zn acetate: 0.1 g, Co, Mn gluconate each 0.005 g.
[0061] Weitere Zusätze:[0061] Further additives:
Glukose, Sorbit, Mannit je 0,1-0,5 g, Zitronensäure 1-5 g, Apfelsäure 1-2 g, Bernsteinsäure 5-15 g, Ethanol 10-50ml, Benzylalkohol 1-4ml., Glyzerin 0.4-1.Og/I, N-Methylglucamin <0,5 g, Na-Iactat 1-4 g, Na-succinat 2-15 g, Natriumchlorid 1-10 g, Konservierung ggf. ohne.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.
[0062] 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, e.g. the amino acids Glu, Asp, Val, Tyr, Phe, Isoleu, Leu in 2N NaOH, xanthine in 3N NaOH, guanine in 3N HCl.
Nach Auffüllen mit bidest. Wasser auf 11 Endvolumen wurde nochmals der pH eingestellt und sterilfilriert.After filling with bidist. Water was adjusted to 11 final volumes again the pH and sterile filtered.
[0063] Beispiel 2Example 2
Synthetischer Extrakt I plus H 38 (später Y 20):Synthetic extract I plus H 38 (later 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 aufgefüllt.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.
[0064] Der gemessene Atmungssteigerungsfaktor betrug 2,6.The measured breathing increase factor was 2.6.
[0065] Beispiel 3Example 3
PADBERG Methode:PADBERG method:
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.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.
[0066] 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 einFor 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 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.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.
[0067] 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 3 [0068] 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.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.
[0069] 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 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.
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).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][0070]
Vergleichsbeispiel 4 [0071] WARBURG Methode - VersuchComparative Example 4 WARBURG method - test
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 02-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, 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.
[0072] MessplanMeasurement plan
Beispiel: Roggen Plazenta Extrakt mit Faktor 1,83. Kontrolle: 1,0 (Pre-Inkubation 1 h bei 37°C):Example: rye placenta extract with a factor of 1.83. Control: 1.0 (pre-incubation 1 h at 37 ° C):
[0073][0073]
Tabelle 4Table 4
_____ ________ : * ï , » » s j , , , ·! Γ j_____ ________: * ï, »» s j,,, ·! Γ j
Tabelle 5 [0074]Table 5
Beispiel 5 [0075] In analoger Weise zu Vergleichsbeispiel 4 wurden Atmungssteigerungsfaktoren gemessen für synthetisches Ex trakt I, synthetisches Extrakt II, synthetischen Kamelleber- Extrakt und für Kamel-NGF (Nerve Growth Promoting Factor)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)
[0077] 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 Kamel-Speicheldrüse, mit einer biologischen Aktivität in BU von 0,010- 0,019 pg/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, 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).
[0078] 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 weitersteigern.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.
Beispiel 6 [0079] im Folgenden sind Ergebnisse von Aktivitätstests für synthetisches Extrakt I und zum Vergleich Schweine-Plazenta-Extrakt aufgeführt sowie Hinweise auf die angewandten Arbeitsmethoden: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:
Tabelle 7 [0080]Table 7
Beschreibung der Methodik in «Re-Reading», Part IV, p 448-456: IBSN 978-1-882292-36-3Description of the methodology in “Re-Reading”, Part IV, p 448-456: IBSN 978-1-882292-36-3
Methodik in «Cosmetics and Toiletries» 92, 25-27 (1977) [0081] Beginn der Metamorphose beim Kamel-Plazenta synthetisch I 5-8 Tage vor Kontrolle, wohingegen bei SchweinePlazenta synthetisch I 3-4 Tage vor Kontrolle (vgl. Tabelle 7).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 ).
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| JP2019522946A JP7022126B2 (en) | 2016-11-04 | 2016-11-29 | Synthetic camel organ extract, its manufacturing method and its use |
| PCT/EP2016/079098 WO2018082795A1 (en) | 2016-11-04 | 2016-11-29 | Synthetic camel organ extracts, method for the preparation and use thereof |
| 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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