WO1993003746A1 - Preparation of medicaments containing the peptidoglycan monomer or its derivatives - Google Patents
Preparation of medicaments containing the peptidoglycan monomer or its derivatives Download PDFInfo
- Publication number
- WO1993003746A1 WO1993003746A1 PCT/EP1992/001859 EP9201859W WO9303746A1 WO 1993003746 A1 WO1993003746 A1 WO 1993003746A1 EP 9201859 W EP9201859 W EP 9201859W WO 9303746 A1 WO9303746 A1 WO 9303746A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- pgm
- carboxylic acid
- acid group
- stands
- immunosuppressive
- Prior art date
Links
- YASBIWJBLQVJGF-UHFFFAOYSA-N N[I]([IH]I)[IH][IH][IH]I Chemical compound N[I]([IH]I)[IH][IH][IH]I YASBIWJBLQVJGF-UHFFFAOYSA-N 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
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/14—Peptides containing saccharide radicals; Derivatives thereof, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
Definitions
- the present invention relates to the use of the peptidoglycan monomer (PGM), its N-acyl derivatives, and its metal complexes in the preparation of medicaments for the correction of the immunosuppressive and hepatosuppressive effects of anaesthetics and operative stress in surgical treatment or in other immunosuppressive, immunodeficient, and hepatosuppressive states, to achieve a swift and safe recovery of the patients.
- PGM peptidoglycan monomer
- N-acyl derivatives N-acyl derivatives
- metal complexes in the preparation of medicaments for the correction of the immunosuppressive and hepatosuppressive effects of anaesthetics and operative stress in surgical treatment or in other immunosuppressive, immunodeficient, and hepatosuppressive states
- the biologically active substance peptidoglycan monomer was made available by biosynthesis (in accordance with YU Patent 35040) and isolated as a chemically defined compound (according to Klaic B. Carbohydr. Res. (1982) 110:320; YU Patent 40 472; AT Patent Specification 362740); later, there were prepared its N-acyl derivatives (YU Pat. Appl. P-626/89; Eur. Pat. Appl. EP 39 00 93), and its metal complexes (YU Pat Appl. P-1982/86; Eur. Pat. Appl. EP 268271).
- the isolated substances are well-soluble in water and physiological solution, non-toxic, and apyrogenic. They demonstrate immunostimulating, antimetastatic, and antitumour activity.
- the object of the present invention is the novel use of the peptidoglycan monomer (PGM), and its N-acyl derivatives of the formula I
- R stands for hydrogen
- Ac stands for a straight (C 2 - C 18 alkyl) carboxylic acid group, or a branched (C 5 - C 18 alkyl) carboxylic acid group, or an unsaturated (C 12 - C 18 alkenyl) carboxylic acid group, or an aromatic (C 7 - C 12 ) carboxylic acid group
- X stands for a hydrogen, or an alkali metal, or an alkaline earth metal, or a quaternary ammonium salt of an organic base, and complexes thereof with bivalent metals of the formulae la or lb
- mice were placed into hermetically closed 1-L metabolic cages containing soda lime, into which air (a flow of 350 mL/min) with added 0.5-1% of halothane was charged by means of a respirator for small animals. The narcosis was maintained for 1 hour. Animals in the control group were subjected to the same procedure, with the exception of halothane in the air for 1 hour. A sub-group of mice was exposed only to halothane anaesthesia, whereas, a sub-group was additionally subjected to operative stress in the form of laparotomy. This operation preceded the exposure of the animals to halothane anaesthesia, and was performed under short ether narcosis.
- the control groups for laparotomy + halothane were also immediately before halothane anaesthesia subjected to a short ether narcosis.
- the animals were then immunized: a) with sheep erythrocytes (OE), and the number of plaques in the spleen was analyzed on the 4th day after the sensibilisation; b) with allogeneic tumour cells, and the growth of the sarcoma I (from A/J mice) and their rejection time; and c) paternal splenocytes for the analysis of the local reaction of the donor cells (BALB/c) against the recipient (BALB/c x CBA)F 1 hybrid.
- OE sheep erythrocytes
- halothane-induced diminishment of the humoral immune response was accompanied by hypoplasia of the bone marrow and the spleen, and the assessment of the decreased proportion of CD4 and CD8 + cells, and the increase of the number of cells not belonging to this phenotype. (Fig.2).
- PGM and its N-acyl derivatives and complexes with bivalent metals or mixtures thereof may be administered intravenously, intraperitoneally, intramuscularly, and subcutaneously, in composition with other nontoxical, physiologically acceptable substances known in the art
- the unit dose size and form depend on the body weight and the individual state of the organism.
- PGM and its N-acyl derivatives and complexes with bivalent metals may be administered in a dose of 5-50 mg per kg of body weight
- mice were given one intraperitoneal injection of PGM dissolved in 0.05 mL of physiological solution immediately after laparotomy and OE-sensibilization, and immediately before halothane anaesthesia.
- Table 2 shows that the best correction of halothane immunosuppression was achieved with a low PGM dose, and the simultaneously performed investigation of the PGM effect in non-anaesthetized mice demonstrated that the effect was achieved only in immunosuppressed mice.
- the plaque generation increase in anaesthetized PGM-treated mice was accompanied by the bone-marrow cell augmentation and an expressed periphereal leukocytosis.
- the PGM-Zn complex dissolved in physiological solution was injected in the same dose as in the foregoing Example (10 mg/kg) in anaesthetized and non-anaesthetized OE-treated mice.
- the experiment was repeated three times, and in all investigations PGM-Zn demonstrated an improved immunocorrective activity in comparison with PGM. and increased the plaque generation in anaesthetized mice for 73.5 %, 73.1 %, and 101.4 %, with respect to the control injected only with physiological solution.
- PGM and its analogues were tested in local GVHR in which they were administered immediately after the injection of paternal splenocytes into the hind leg pad of F1 hybrids, or immediately before halothane anaesthesia. It was found, that PGM-Zn potentiates the response on the popliteal lymphatic node level on the 7th day after the injection, whereas, PGM-L-Na significantly increases the number of large lymphatic cells in the local lymphatic node on day 10 after the injection (assessed by means of counter-flow cytometer).
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Psychiatry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Rheumatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP5504098A JPH08506796A (en) | 1991-08-15 | 1992-08-13 | Use of peptidoglycan monomer (PGM), its N-acyl derivative and its metal complex for the preparation of a drug for correcting the immunosuppressive state and hepatic suppressive state in vivo |
CS94301A CZ30194A3 (en) | 1991-08-15 | 1992-08-13 | The use of peptidoglycan monomer (pgm), n-acyl derivatives and complexes with metal thereof when preparing medicaments for correction immuno=suppressive and hepato-suppressive states of organism |
EP92917699A EP0600974A1 (en) | 1991-08-15 | 1992-08-13 | Preparation of medicaments containing the peptidoglycan monomer or its derivatives |
SK179-94A SK17994A3 (en) | 1991-08-15 | 1992-08-13 | Usage of a peptidoglycan monomer, its n-acyl derivatives and its metal complexes in the preparation of medicaments |
BG98628A BG98628A (en) | 1991-08-15 | 1994-03-01 | The use of peptidoglycan monomer (pgm) and its n-acyl derivatives and metal complexes for the production of medicines for the correction of immunosuppressive and hepatosuppressive conditions of the organism |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
YUP-1412/91 | 1991-08-15 | ||
YU141291 | 1991-08-15 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1993003746A1 true WO1993003746A1 (en) | 1993-03-04 |
Family
ID=25554075
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1992/001859 WO1993003746A1 (en) | 1991-08-15 | 1992-08-13 | Preparation of medicaments containing the peptidoglycan monomer or its derivatives |
Country Status (10)
Country | Link |
---|---|
EP (1) | EP0600974A1 (en) |
JP (1) | JPH08506796A (en) |
BG (1) | BG98628A (en) |
CA (1) | CA2115270A1 (en) |
CZ (1) | CZ30194A3 (en) |
HR (1) | HRP920488A2 (en) |
HU (1) | HU9400420D0 (en) |
RU (1) | RU94027699A (en) |
SK (1) | SK17994A3 (en) |
WO (1) | WO1993003746A1 (en) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0268271A2 (en) * | 1986-11-19 | 1988-05-25 | SOUR PLIVA farmaceutska, Kemijska prehrambena i kozmeticka industrija, n.sol.o. | Metal complexes of n-acetyl-glucosaminyl-n-acetal-muramoyl-l-alanyl-d-isoglutaminyl-(l)-meso-diamino-pimelyl-(d-amide)-(l)-d-alanyl-d-alanine and their use in the manufacture of pharmaceuticals |
US4868155A (en) * | 1987-10-05 | 1989-09-19 | Merck & Co., Inc. | Dipeptidyl 4-0-,6-0-acyl-2-amino-2-deoxy-D-glucose compositions and methods of use in AIDS-immunocompromised human hosts |
EP0390039A2 (en) * | 1989-03-27 | 1990-10-03 | Pliva Farmaceutska, Kemijska, Prehrambena I Kozmeticka Industrija S P.O. | N-Acyl derivatives of the peptidoglycan monomer, pharmaceutically acceptable salts thereof, their preparation and use in the manufacture of immunomodulators and immunoadjuvants |
-
1992
- 1992-08-13 CZ CS94301A patent/CZ30194A3/en unknown
- 1992-08-13 SK SK179-94A patent/SK17994A3/en unknown
- 1992-08-13 CA CA002115270A patent/CA2115270A1/en not_active Abandoned
- 1992-08-13 HU HU9400420A patent/HU9400420D0/en unknown
- 1992-08-13 WO PCT/EP1992/001859 patent/WO1993003746A1/en not_active Application Discontinuation
- 1992-08-13 RU RU94027699/14A patent/RU94027699A/en unknown
- 1992-08-13 JP JP5504098A patent/JPH08506796A/en active Pending
- 1992-08-13 EP EP92917699A patent/EP0600974A1/en not_active Withdrawn
- 1992-09-25 HR HR920488A patent/HRP920488A2/en not_active Application Discontinuation
-
1994
- 1994-03-01 BG BG98628A patent/BG98628A/en unknown
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0268271A2 (en) * | 1986-11-19 | 1988-05-25 | SOUR PLIVA farmaceutska, Kemijska prehrambena i kozmeticka industrija, n.sol.o. | Metal complexes of n-acetyl-glucosaminyl-n-acetal-muramoyl-l-alanyl-d-isoglutaminyl-(l)-meso-diamino-pimelyl-(d-amide)-(l)-d-alanyl-d-alanine and their use in the manufacture of pharmaceuticals |
US4868155A (en) * | 1987-10-05 | 1989-09-19 | Merck & Co., Inc. | Dipeptidyl 4-0-,6-0-acyl-2-amino-2-deoxy-D-glucose compositions and methods of use in AIDS-immunocompromised human hosts |
EP0390039A2 (en) * | 1989-03-27 | 1990-10-03 | Pliva Farmaceutska, Kemijska, Prehrambena I Kozmeticka Industrija S P.O. | N-Acyl derivatives of the peptidoglycan monomer, pharmaceutically acceptable salts thereof, their preparation and use in the manufacture of immunomodulators and immunoadjuvants |
Non-Patent Citations (1)
Title |
---|
PERIODICUM BIOLOGORUM vol. 92, no. SUP3, October 1990, ZAGREB, CROATIA page 44 Z. TROBONJACA ET AL. 'CORRECTION OF HALOTHANE AND OPERATIVE STRESS INDUCED IMMUNOSUPPRESSION BY IGF-1, INDOMETHACIN AND PEPTIDOGLYCAN MONOMERS.' SEE ABSTRACT Nr. 41 * |
Also Published As
Publication number | Publication date |
---|---|
BG98628A (en) | 1995-06-30 |
JPH08506796A (en) | 1996-07-23 |
RU94027699A (en) | 1996-04-10 |
HU9400420D0 (en) | 1994-08-29 |
EP0600974A1 (en) | 1994-06-15 |
HRP920488A2 (en) | 1994-08-31 |
CZ30194A3 (en) | 1994-06-15 |
SK17994A3 (en) | 1994-08-10 |
CA2115270A1 (en) | 1993-03-04 |
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