DE3501560A1 - Protein hydrolysates, process for their preparation and pharmaceutical compositions containing these - Google Patents
Protein hydrolysates, process for their preparation and pharmaceutical compositions containing theseInfo
- Publication number
- DE3501560A1 DE3501560A1 DE19853501560 DE3501560A DE3501560A1 DE 3501560 A1 DE3501560 A1 DE 3501560A1 DE 19853501560 DE19853501560 DE 19853501560 DE 3501560 A DE3501560 A DE 3501560A DE 3501560 A1 DE3501560 A1 DE 3501560A1
- Authority
- DE
- Germany
- Prior art keywords
- lactalbumin
- lysozyme
- protein hydrolyzate
- water
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 239000003531 protein hydrolysate Substances 0.000 title claims abstract description 9
- 108010009736 Protein Hydrolysates Proteins 0.000 title abstract description 3
- 238000002360 preparation method Methods 0.000 title description 5
- 238000000034 method Methods 0.000 title description 3
- 239000008194 pharmaceutical composition Substances 0.000 title description 2
- 102000004407 Lactalbumin Human genes 0.000 claims abstract description 14
- 108090000942 Lactalbumin Proteins 0.000 claims abstract description 14
- 108010014251 Muramidase Proteins 0.000 claims abstract description 9
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 claims abstract description 9
- 229960000274 lysozyme Drugs 0.000 claims abstract description 9
- 239000004325 lysozyme Substances 0.000 claims abstract description 9
- 235000010335 lysozyme Nutrition 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 239000004365 Protease Substances 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 108090000526 Papain Proteins 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 108010019160 Pancreatin Proteins 0.000 claims description 5
- 108091005804 Peptidases Proteins 0.000 claims description 5
- 229940055695 pancreatin Drugs 0.000 claims description 5
- 239000000725 suspension Substances 0.000 claims description 4
- 239000004382 Amylase Substances 0.000 claims description 3
- 102000013142 Amylases Human genes 0.000 claims description 3
- 108010065511 Amylases Proteins 0.000 claims description 3
- 235000019418 amylase Nutrition 0.000 claims description 3
- 239000000706 filtrate Substances 0.000 claims description 3
- 108090000317 Chymotrypsin Proteins 0.000 claims description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims description 2
- 108090000631 Trypsin Proteins 0.000 claims description 2
- 102000004142 Trypsin Human genes 0.000 claims description 2
- 229960002376 chymotrypsin Drugs 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 235000019419 proteases Nutrition 0.000 claims description 2
- 239000012588 trypsin Substances 0.000 claims description 2
- 102000016943 Muramidase Human genes 0.000 claims 2
- 239000012141 concentrate Substances 0.000 claims 1
- 239000008177 pharmaceutical agent Substances 0.000 claims 1
- 102100033468 Lysozyme C Human genes 0.000 abstract description 7
- 230000007515 enzymatic degradation Effects 0.000 abstract 1
- 239000000047 product Substances 0.000 description 10
- 108010046377 Whey Proteins Proteins 0.000 description 6
- 229940055729 papain Drugs 0.000 description 6
- 235000019834 papain Nutrition 0.000 description 6
- 235000021119 whey protein Nutrition 0.000 description 6
- 108010076119 Caseins Proteins 0.000 description 5
- 102000011632 Caseins Human genes 0.000 description 5
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 5
- 235000021240 caseins Nutrition 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 102000035195 Peptidases Human genes 0.000 description 3
- 229940021722 caseins Drugs 0.000 description 3
- 235000020247 cow milk Nutrition 0.000 description 3
- 235000013336 milk Nutrition 0.000 description 3
- 239000008267 milk Substances 0.000 description 3
- 210000004080 milk Anatomy 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102000014171 Milk Proteins Human genes 0.000 description 2
- 108010011756 Milk Proteins Proteins 0.000 description 2
- BYPFEZZEUUWMEJ-UHFFFAOYSA-N Pentoxifylline Chemical compound O=C1N(CCCCC(=O)C)C(=O)N(C)C2=C1N(C)C=N2 BYPFEZZEUUWMEJ-UHFFFAOYSA-N 0.000 description 2
- 239000005018 casein Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 235000021239 milk protein Nutrition 0.000 description 2
- 230000000945 opiatelike Effects 0.000 description 2
- 229960001476 pentoxifylline Drugs 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
- DEXFNLNNUZKHNO-UHFFFAOYSA-N 6-[3-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-3-oxopropyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)C(CCC1=CC2=C(NC(O2)=O)C=C1)=O DEXFNLNNUZKHNO-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 230000002498 deadly effect Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- AIUDWMLXCFRVDR-UHFFFAOYSA-N dimethyl 2-(3-ethyl-3-methylpentyl)propanedioate Chemical class CCC(C)(CC)CCC(C(=O)OC)C(=O)OC AIUDWMLXCFRVDR-UHFFFAOYSA-N 0.000 description 1
- 235000014103 egg white Nutrition 0.000 description 1
- 210000000969 egg white Anatomy 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 229940066779 peptones Drugs 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229920005990 polystyrene resin Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 108010009004 proteose-peptone Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000002336 sorption--desorption measurement Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229960001322 trypsin Drugs 0.000 description 1
- 235000021241 α-lactalbumin Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/01—Hydrolysed proteins; Derivatives thereof
- A61K38/012—Hydrolysed proteins; Derivatives thereof from animals
- A61K38/018—Hydrolysed proteins; Derivatives thereof from animals from milk
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Abstract
Description
Proteinhydrolysate, Verfahren zu ihrer Herstellung undProtein hydrolysates, processes for their preparation and
diese enthaltende pharmazeutische Mittel Die Erfindung betrifft ein Proteinhydrolysat, das aus Lactalbumin gewonnen wird, ein Verfahren zur Herstellung dieses Hydrolysates und seine Verwendung für pharmazeutische Zwecke.pharmaceutical compositions containing them The invention relates to a protein hydrolyzate obtained from lactalbumin, a process for the production of this hydrolyzate and its use for pharmaceutical purposes.
Bekanntlich setzen sich die Proteine der Milch zusammen aus den Seinen und Molkenproteinen. Außerdem können die Proteose-Peptone mit einem Anteil am Gesamtstickstoffgehalt der Kuhmilch von etwa 5 % zu den Proteinen gerechnet werden. Der Anteil der Caseine am Gesamt-Proteingehalt der Kuhmilch beträgt etwa 80 %, der an Molken-Proteinen etwa 20 %. Die Caseine gehören zu den am besten erforschten Proteinen. Im Gegensatz zu den ursprünglichen Annahmen sind sie keineswegs einheitliche Körper. Bisher sind mehrere Fraktionen unterschieden worden. Typisch für alle Caseine ist jedoch, daß sie gebundenen Phosphor enthalten. Sie sind sehr viel komplexer aufgebaut und haben ein wesentlich größeres Molekulargewicht als die sogenannten Molken-Proteine.As is well known, the proteins in milk are made up of its own and whey proteins. In addition, the proteose peptones can contribute to the total nitrogen content 5% of cow's milk can be counted among the proteins. The proportion of caseins of the total protein content of cow's milk is around 80%, that of whey proteins about 20%. The caseins are among the best-researched proteins. In contrast compared to the original assumptions, they are by no means unitary bodies. So far are several factions have been distinguished. However, it is typical of all caseins that they contain bound phosphorus. They are structured and have a much more complex structure a much larger molecular weight than the so-called whey proteins.
Von den Molken-Proteinen ist bisher bekannt, daß sie aus B-Lactoglobulin, a-Lactalbumin, Serumalbumin und Immunglobulinen bestehen.It is known that whey proteins are derived from B-lactoglobulin, α-lactalbumin, serum albumin and immunoglobulins are made up.
Untersuchungen von Brantl und Teschemacher (Milchwissenschaft 37, Seiten 641 - 644, 1982) haben gezeigt, daß opiatartig wirkende Stoffe aus der Caseinfraktion von Rindermilch isoliert werden können. Ausgehend von käufliches Casein-Pepton haben diese Autoren einen Chloroform-Methanol 65:35 (v/v) Extrakt angefertigt und diesen über zwei Adsorptions-/Desorptionsschritte an Aktivkohle bzw. XAD-2-Polystyrolharz vorgereinigt und mittels HPLC weitergereinigt. Die Opiataktivität des jeweils erhaltenen Materials wurde am Meerschweinchen-Ileum-Präparat bestimmt und so die Anreicherung bzw.Investigations by Brantl and Teschemacher (Milchwissenschaft 37, Pages 641-644, 1982) have shown that opiate-like substances from the casein fraction can be isolated from bovine milk. Starting from commercially available casein peptone these authors prepared a chloroform-methanol 65:35 (v / v) extract and this via two adsorption / desorption steps on activated carbon or XAD-2 polystyrene resin pre-cleaned and Purified further by means of HPLC. The opiate activity the material obtained in each case was determined on the guinea pig ileum preparation and so the enrichment resp.
Reinigung quantitativ verfolgt. Die opiatartige Wirkung wurde einem Heptapeptid und seinen am C-Terminus um eine oder mehrere Aminosäurereste verkürzten Fragmenten zugeordnet.Purification tracked quantitatively. The opiate-like effects became one Heptapeptide and its C-terminus shortened by one or more amino acid residues Assigned to fragments.
Der Erfindung liegt die Aufgabe zugrunde, aus MiLchproteinen weitere pharmazeutisch brauchbare Bestandteile bereitzustellen.The invention is based on the object of producing further milk proteins to provide pharmaceutically acceptable ingredients.
Überraschenderweise wurde nun gefunden, daß ausgehend von Molken-Proteinen oder von denaturiertem Lysozym Abbauprodukte gewonnen werden können, die überraschende pharmakologische Wirkungen besitzen. Insbesondere Abbauprodukte von Lactalbumin, das nur etwa 2 - 5 % der Milch-Proteine bzw. etwa 24 % der Molken-Proteine ausmacht, und von denaturiertem Lysozym zeigten überraschende pharmakologische Wirkungen. Aufgrund der oben erwähnten Arbeiten war man bisher der Auffassung, daß pharmakologisch wirksame Bestandteile der Milch nur in der Casein-Fraktion vorkommen. Lysozym ist in seinem Aufbau dem Lactalbumin ähnlich. In beiden Proteinen sind 51 Aminosäuren identisch und 24 ähnlich angeordnet.Surprisingly, it has now been found that starting from whey proteins or from denatured lysozyme degradation products can be obtained, the surprising have pharmacological effects. In particular, lactalbumin breakdown products, which only makes up about 2 - 5% of milk proteins or about 24% of whey proteins, and from denatured lysozyme showed surprising pharmacological effects. Based on the work mentioned above, it was previously of the opinion that pharmacologically effective components of milk only occur in the casein fraction. Is lysozyme similar in structure to lactalbumin. There are 51 amino acids in both proteins identical and 24 arranged similarly.
Lysozym kommt in geringer Menge in der Kuhmilch vor in größerer Menge im Hühnereiweiß und in Schleimhäuten.Lysozyme occurs in small amounts in cow's milk in larger amounts in egg white and in mucous membranes.
Das erfindungsgemäße Proteinhydrolysat ist dadurch erhältlich, daß man aus Lactalbumin oder Lysozym und Wasser eine Suspension herstellt, die etwa 3 bis 5 i Lactalbumin oder Lysozym enthält, dieser Suspension bei Raumtemperatur etwa 0,01 - 2 Gew.-%, bezogen auf die Suspension, mindestens eine handelsübliche Protease und gegebenenfalls eine Amylase zusetzt,- das Gemisch zuerst einige Stunden bei etwa 380C später bei etwa 600C rührt, bis die Mischung etwas aufklart, gegebenenfalls kurz 0 auf 80 - 90 C erhitzt, abkühlen läßt, dann bei reduziertem Druck einengt, den Rückstand in einem Alkohol/ Wasser-Gemisch 70:30 (v/v) aufnimmt, etwas Aktivkohle zusetzt und dann filtriert. Aus dem erhaltenen Filtrat wird durch Einengen zur Trockne das praktisch farblose Produkt isoliert.The protein hydrolyzate according to the invention is obtainable in that a suspension is made from lactalbumin or lysozyme and water, which is about This suspension contains 3 to 5 liters of lactalbumin or lysozyme at room temperature about 0.01-2% by weight, based on the suspension, at least one commercially available Add protease and, if necessary, an amylase, - the mixture first for a few hours stir at about 380C later at about 600C, until the mixture is something clears, if necessary briefly heated to 80-90 C, allowed to cool, then at reduced The pressure is reduced, the residue is absorbed in an alcohol / water mixture 70:30 (v / v), added some activated charcoal and then filtered. From the filtrate obtained is through Concentrating to dryness isolates the practically colorless product.
Geeignete Proteasen sind z.B. Papain, Pankreatin, Chymotrypsin und Trypsin.Suitable proteases are e.g. papain, pancreatin, chymotrypsin and Trypsin.
Die erfindungsgemäßen Proteinhydrolysate haben ein breites Wirkungsspektrum, sie eignen sich besonders zur oralen und topischen Behandlung von schmerzhaften Entzündungen. Der Wirkstoff kann zusammen mit üblichen festen oder flüssigen pharmazeutischen Trägern zu üblichen Darbietungsformen wie Tabletten, Pulvern, Granulaten aber auch zu Injektionspräparaten verarbeitet werden.The protein hydrolyzates according to the invention have a broad spectrum of activity, they are particularly suitable for the oral and topical treatment of painful Inflammation. The active ingredient can be used together with conventional solid or liquid pharmaceutical But also carriers for the usual forms of presentation such as tablets, powders, granules can be processed into injection preparations.
Das erfindungsgemäße Produkt wurde im Mäuseversuch auf folgende Weise pharmakologisch getestet: Eine Pentoxifyllin-Dosis von etwa 300 mg/kg, i.p. ist normalerweib tötlich für eine Maus. Verabreicht man jedoch etwa 30 Minuten vorher das erfindungsgemäße Produkt in einer Dosis von etwa 600 mg/kg intraperitonial oder intravenös, so erreicht man einen 1008-igen Schutzeffekt gegenüber der Pentoxifyllin-induzierten Mortalität.The product according to the invention was tested in mice in the following manner pharmacologically tested: a pentoxifylline dose of about 300 mg / kg, i.p. is normally deadly for a mouse. However, it is administered about 30 minutes beforehand the product according to the invention in a dose of about 600 mg / kg intraperitoneally or intravenously, a 1008% protective effect is achieved against the pentoxifylline-induced Mortality.
Die nachfolgenCien Beispiele dienen zur weiteren Erläuterung der Herstellung der erfindungsgemäßen Substanz: Beispiel 1 5 g Lactalbumin werden in 95 ml Wasser suspendiert, unter Rühren gibt man 1 g käufliche Proteasen hinzu und erwärmt auf 38 0C. Bei dieser Temperatur rührt man mehrere Stunden bis das Reaktionsgemisch annähernd klar ist.The following examples serve to further explain the preparation of the substance according to the invention: Example 1 5 g of lactalbumin are dissolved in 95 ml of water suspended, under 1 g of commercially available proteases is added while stirring and heated to 38 0C. The reaction mixture is stirred for several hours at this temperature is almost clear.
Sodann wird kurz auf 60 0C erhitzt, abgekühlt und im Vakuum eingeengt. Der Rückstand wird in 100 ml Ethanol/ Wasser 70:30 (v/v) aufgenommen, mit etwas Aktivkohle versetzt, filtriert und das Filtrat wird zur Trockne eingeengt. Man erhält ein praktisch farbloses Produkt in etwa 70 - 80%-iger Ausbeute.It is then briefly heated to 60 ° C., cooled and concentrated in vacuo. The residue is taken up in 100 ml of ethanol / water 70:30 (v / v), with something Active charcoal is added, the mixture is filtered and the filtrate is concentrated to dryness. You get a practically colorless product in about 70-80% yield.
Beispiel 2 5 g Lactalbumin werden in 130 ml Wasser suspendiert, man gibt 50 mg Papain und 50 mg Pankreatin hinzu, erwärmt auf 380C, rührt bei dieser Temperatur etwa 3 Stunden lang, gibt 50 mg einer handelsüblichen Amylase hinzu und steigert die Temperatur langsam 0 (innerhalb von etwa 2 - 3 Stunden) auf 60 C. Bei dieser Temperatur rührt man weitere 2 Stunden, dann erhöht man die Temperatur kurz auf 80 - 900C, läßt abkühlen, engt die trübe Lösung im Vakuum ein, nimmt den Rückstand in Ethanol/Wasser (70/30 v/v) auf, filtriert und engt im Vakuum ein. Man erhält etwa 2 g Produkt.Example 2 5 g of lactalbumin are suspended in 130 ml of water, man add 50 mg papain and 50 mg pancreatin, heat to 380C, stir at this Temperature about 3 hours, add 50 mg of a commercial amylase and the temperature slowly increases from 0 (within approx. 2 - 3 hours) to 60 C. At This temperature is stirred for a further 2 hours, then the temperature is increased briefly to 80-900C, allowed to cool, the cloudy solution is concentrated in vacuo, the residue is taken up in ethanol / water (70/30 v / v), filtered and concentrated in vacuo. You get about 2 g of product.
Beispiel 3 Analog Beispiel 2 werden 5 g Lactalbumin in 130 ml Wasser suspendiert. Man gibt jeweils 50 mg von zwei proteolytischen Enzymen, z.B. Papain und Pankreatin 0 hinzu, erwärmt auf 38 C und rührt etwa 6 Stunden lang bei dieser Temperatur. Anschließend wird die Temperatur langsam auf 600C erhöht und etwa 2 Stunden lang unter Rühren beibehalten. Dann wird kurz auf 80 - 90 0C aufgeheizt und gemäß Beispiel 2 aufgearbeitet. Man erhält etwa 1,8 g Produkt.Example 3 Analogously to Example 2, 5 g of lactalbumin are dissolved in 130 ml of water suspended. 50 mg of two proteolytic enzymes, e.g. papain, are given each time and pancreatin 0, warmed to 38 C and stirred for about 6 hours at this Temperature. Then the temperature is slowly increased to 600C and about 2 Maintain stirring for hours. Then it is briefly heated to 80 - 90 ° C and worked up according to Example 2. About 1.8 g of product are obtained.
Beispiel 4 Analog Beispiel 2 werden 5 g Lactalbumin in 130 ml Wasser suspendiert. Man gibt 50 mg Papain hinzu, erwärmt auf 380C, rührt 6 Stunden lang bei dieser Temperatur, gibt erneut 50 mg Papain hinzu, steigert die Temperatur langsam auf 6OOC, rührt bei dieser Temperatur etwa 2 Stunden lang weiter, erhitzt kurz auf 80 - 90 0C und engt nach dem Abkühlen das Gemisch im Vakuum zur Trockene ein. Der oben beschriebene pharmakologische Test zeigt, daß dieses Produkt bereits für pharmazeutische Zwecke geeignet ist. Behandelt man anschließend mit Ethanol/Wasser, wie in Beispiel 2 beschrieben, so erhält man etwa 1,7 g Produkt.Example 4 Analogously to Example 2, 5 g of lactalbumin are dissolved in 130 ml of water suspended. 50 mg of papain are added, the mixture is warmed to 380 ° C. and stirred for 6 hours at this temperature, add another 50 mg papain, the temperature slowly increases to 60OC, stir at this temperature for about 2 hours, heated up briefly 80-90 ° C. and, after cooling, the mixture is concentrated to dryness in a vacuum. Of the The pharmacological test described above shows that this product is already suitable for pharmaceutical Purposes. It is then treated with ethanol / water, as in the example 2, about 1.7 g of product are obtained.
Beispiel 5 5 g Lactalbumin werden gemäß den Angaben des Beispiels 4 suspendiert und behandelt jedoch wird anstelle von Papain in diesem Falle Pankreatin verwendet. Nach der Alkohol/Wasser-Behandlung erhält man etwa 2,1 g Produkt.Example 5 5 g of lactalbumin are obtained as described in the example 4 suspended and treated, however, instead of papain, pancreatin is used in this case used. After the alcohol / water treatment, about 2.1 g of product are obtained.
Claims (3)
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19853501560 DE3501560A1 (en) | 1985-01-18 | 1985-01-18 | Protein hydrolysates, process for their preparation and pharmaceutical compositions containing these |
| US06/918,253 US4918008A (en) | 1985-01-18 | 1986-01-20 | Process for the preparation of protein hydrolysate and medicaments containing these hydrolysates |
| JP61500802A JPH0732718B2 (en) | 1985-01-18 | 1986-01-20 | Protein hydrolyzate and method for producing the same |
| EP86900765A EP0210204B1 (en) | 1985-01-18 | 1986-01-20 | Protein hydrolysates, production process and drugs containing th em |
| AT86900765T ATE39046T1 (en) | 1985-01-18 | 1986-01-20 | PROTEIN HYDROLYSATE, PROCESS FOR THEIR MANUFACTURE AND MEDICATIONS CONTAINING SUCH HYDROLYSATE. |
| PCT/EP1986/000016 WO1986004217A2 (en) | 1985-01-18 | 1986-01-20 | Protein hydrolysates, production process and drugs containing th em |
| DE8686900765T DE3661339D1 (en) | 1985-01-18 | 1986-01-20 | Protein hydrolysates, production process and drugs containing th em |
| AU53594/86A AU583592B2 (en) | 1985-01-18 | 1986-01-20 | Protein hydrolysates for pharmaceutical use |
| DK446386A DK446386D0 (en) | 1985-01-18 | 1986-09-17 | PROTEIN HYDROOLYCATES, PROCEDURES FOR PREPARING THEREOF, AND PHARMACEUTICALS CONTAINING THESE HYDROLYCATES |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19853501560 DE3501560A1 (en) | 1985-01-18 | 1985-01-18 | Protein hydrolysates, process for their preparation and pharmaceutical compositions containing these |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE3501560A1 true DE3501560A1 (en) | 1986-07-24 |
Family
ID=6260155
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19853501560 Withdrawn DE3501560A1 (en) | 1985-01-18 | 1985-01-18 | Protein hydrolysates, process for their preparation and pharmaceutical compositions containing these |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE3501560A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105713210A (en) * | 2014-12-05 | 2016-06-29 | 中国石油化工股份有限公司 | Method of preparing lignin from residual dregs in fiber ethanol rectifying still bottom |
| US10653613B2 (en) | 2013-12-18 | 2020-05-19 | Dsm Ip Assets B.V. | Compositions comprising lysozyme hydrolysate for use in keratin-containing tissue |
-
1985
- 1985-01-18 DE DE19853501560 patent/DE3501560A1/en not_active Withdrawn
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10653613B2 (en) | 2013-12-18 | 2020-05-19 | Dsm Ip Assets B.V. | Compositions comprising lysozyme hydrolysate for use in keratin-containing tissue |
| EP3082837B1 (en) * | 2013-12-18 | 2020-09-09 | DSM IP Assets B.V. | Compositions comprising lysozyme hydrolysate for use in keratin-containing tissue |
| CN105713210A (en) * | 2014-12-05 | 2016-06-29 | 中国石油化工股份有限公司 | Method of preparing lignin from residual dregs in fiber ethanol rectifying still bottom |
| CN105713210B (en) * | 2014-12-05 | 2018-06-19 | 中国石油化工股份有限公司 | A kind of method that cellulose ethanol rectifying still bottom residue prepares lignin |
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