WO1998058662A1 - Toleranzinduktion durch proteasen - Google Patents
Toleranzinduktion durch proteasen Download PDFInfo
- Publication number
- WO1998058662A1 WO1998058662A1 PCT/EP1998/003758 EP9803758W WO9858662A1 WO 1998058662 A1 WO1998058662 A1 WO 1998058662A1 EP 9803758 W EP9803758 W EP 9803758W WO 9858662 A1 WO9858662 A1 WO 9858662A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- use according
- enzymes
- papain
- bromelain
- trypsin
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/4873—Cysteine endopeptidases (3.4.22), e.g. stem bromelain, papain, ficin, cathepsin H
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4826—Trypsin (3.4.21.4) Chymotrypsin (3.4.21.1)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/001—Preparations to induce tolerance to non-self, e.g. prior to transplantation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
- A61K2039/577—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 tolerising response
Definitions
- the present invention relates to the use of one or more hydrolytic enzymes for tolerance induction against antigens.
- antigenic substances can trigger an immune response in the body.
- this immune response is more or less strong.
- an immune response to the administered antigen is absent or at least is lower, since, for example, the antigen can serve as a drug and the immune system's reaction unnecessarily burdens the body or even makes you sick per se.
- hydrolytic enzymes for inducing tolerance to antigens.
- Proteases are preferably used.
- hydrolytic enzymes are able to induce tolerance to themselves, that is to say that when enzymes are administered orally, the immune system is obviously influenced in such a way that there is no reaction of the immune system to the enzymes. There is therefore no formation of antibodies or specific CD4 cell activation directed against these enzymes and therefore no sensitization, whether probably more than 5% of the enzymes from the intestine are absorbed.
- enzyme inhibitors such as e.g. Aprotinin
- antibody formation and sensitization to the enzymes.
- the enzymes are therefore able to induce tolerance against themselves.
- the cause of this tolerance induction appears to lie in the enzyme action itself. This can be deduced from the fact that the enzyme action by anti-enzymes such as e.g. Aprotinin, is inhibited and the associated tolerance induction by the enzymes decreases or is stopped. This finding forms the basis for the present invention, which aims to deliver one or more hydrolytic enzymes together with the antigen. It was surprisingly found that the enzymes also induce tolerance to these antigens.
- proteases in particular trypsin, chymotrypsin, bromelain and / or papain are optionally used in combination with rutin or a combination thereof.
- the enzymes used according to the invention can be isolated inexpensively from the following raw materials.
- Bromelain is a proteolytically active enzyme from the pineapple juice and can also be isolated from ripe fruit.
- Papain is a proteolytic enzyme obtained from the milk sap of the immature, meaty fruits of the Carica Papaya melon tree. Pure papain is a crystalline polypeptide with an MG. from 23350 consisting of a chain of 212 amino acid residues with 4 disulfide bridges; Sequence and spatial Structure are known. Papain is used in many different ways: due to its protein-splitting properties as "meat tenderizer” or “short salt", for clarifying beer, for bread and hard biscuit production, in leather preparation, in the textile industry for degassing silk and for preventing wool matting, in the tobacco industry for quality improvement, for the recovery of silver from used photographic material, furthermore in bacteriology for the extraction of peptone.
- papain is already used to support enzymatic digestion, for enzymatic wound cleaning and as an additive to denture cleaning agents.
- papain preparations are also offered bound to plastic polymers or agarose carriers.
- Papain has also been used as a catalyst for the synthesis of oligopeptides.
- Trypsin is a proteolytic enzyme that is also formed in the pancreas and is already used therapeutically in conjunction with other enzymes. It belongs to the serine proteinases. Crystalline trypsin has a MW of approx. 23300, is soluble in water but not in alcohol, has an optimum activity at pH 7-9 and cleaves peptide chains specifically on the carboxy side of the basic amino acid residues L-lysine and L-arginine. The spatial structure of the 223 amino acid trypsin is known.
- Chymotrypsin is one of the digestive enzymes. It arises in the pancreas from zymogens under the influence of trypsin. Chymotrypsin belongs to the family of serine proteases due to a catalytic mechanism in which a serine residue is essentially involved.
- the proteases administered are trypsin, chymotrypsin, bromelain, papain, neuraminidase and / or ficin. If necessary, rutin and superoxide dismutase can also be used.
- the enzymes are advantageously administered together with the antigen against which tolerance is to be induced.
- the antigen against which tolerance is to be created is e.g. around the antigen Basic Myelo Protein (BMP), collagen, an autoantigen or an extract from the large and small intestine of Crohn's disease or ulcerative colitis.
- BMP Basic Myelo Protein
- rutin can advantageously be used. Any conceivable route of administration is possible, e.g. oral, parenterai, etc.
- the enzyme and antigen can also be administered in separate dosage forms.
- the combined use of 20 to 100 mg bromelain, 40 to 120 mg papain and 10 to 50 mg trypsin per dose unit is particularly effective.
- a combination of 90 mg bromelain, 120 mg papain and 100 mg rutoside x 3H 2 O is very particularly preferred.
- a combination of 48 mg trypsin, 90 mg bromelain and 100 mg rutoside x 3H 2 O is used.
- 10 to 100 mg, particularly preferably 100 mg of rutoside x 3 H 2 O are used per dose unit.
- 100 mg papain, 40 mg trypsin and 40 mg chymotrypsin are used.
- the medicament can furthermore contain all customary auxiliaries and / or carriers.
- Auxiliaries and carriers include e.g. Lactose, magnesium stearate, stearic acid, talc, methacrylic acid, copolymer type A, Shellack, Makrogol 6000, di-butyl phthalate, vanillin, titanium dioxide, white clay, polyindone, yellow wax and carnauba wax.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Transplantation (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP98937516A EP0920333A1 (de) | 1997-06-20 | 1998-06-19 | Toleranzinduktion durch proteasen |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19726254.6 | 1997-06-20 | ||
DE1997126254 DE19726254C2 (de) | 1997-06-20 | 1997-06-20 | Toleranzinduktion durch Proteasen |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1998058662A1 true WO1998058662A1 (de) | 1998-12-30 |
Family
ID=7833163
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1998/003758 WO1998058662A1 (de) | 1997-06-20 | 1998-06-19 | Toleranzinduktion durch proteasen |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP0920333A1 (de) |
DE (1) | DE19726254C2 (de) |
WO (1) | WO1998058662A1 (de) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4302060A1 (de) * | 1993-01-26 | 1994-07-28 | Mucos Pharma Gmbh & Co | Verwendung von Bromelain zur Krebstherapie und/oder Metastasen-Prophylaxe |
WO1996000082A1 (en) * | 1994-06-24 | 1996-01-04 | Cortecs Limited | Medical use of bromelain |
WO1997024138A2 (en) * | 1995-12-29 | 1997-07-10 | Cortecs (Uk) Limited | Medical use of proteases |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2700088B2 (ja) * | 1991-07-25 | 1998-01-19 | 房則 濱島 | 免疫抑制剤 |
-
1997
- 1997-06-20 DE DE1997126254 patent/DE19726254C2/de not_active Expired - Fee Related
-
1998
- 1998-06-19 EP EP98937516A patent/EP0920333A1/de not_active Ceased
- 1998-06-19 WO PCT/EP1998/003758 patent/WO1998058662A1/de not_active Application Discontinuation
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4302060A1 (de) * | 1993-01-26 | 1994-07-28 | Mucos Pharma Gmbh & Co | Verwendung von Bromelain zur Krebstherapie und/oder Metastasen-Prophylaxe |
WO1996000082A1 (en) * | 1994-06-24 | 1996-01-04 | Cortecs Limited | Medical use of bromelain |
WO1997024138A2 (en) * | 1995-12-29 | 1997-07-10 | Cortecs (Uk) Limited | Medical use of proteases |
Non-Patent Citations (1)
Title |
---|
WOOD G R ET AL: "Sequential effects of an oral enzyme combination with rutosid in different in vitro and in vivo models of inflammation.", INTERNATIONAL JOURNAL OF IMMUNOTHERAPY 13 (3-4). 1997. 139-145, XP002084800 * |
Also Published As
Publication number | Publication date |
---|---|
EP0920333A1 (de) | 1999-06-09 |
DE19726254A1 (de) | 1998-12-24 |
DE19726254C2 (de) | 1999-10-21 |
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