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).

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• 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)
• Neurology (AREA)
• Hematology (AREA)
• Obesity (AREA)
• Addiction (AREA)
• Psychiatry (AREA)
• Biomedical Technology (AREA)
• Diabetes (AREA)
• Neurosurgery (AREA)
• Dermatology (AREA)
• Rheumatology (AREA)
• Proteomics, Peptides & Aminoacids (AREA)
• Epidemiology (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Peptides Or Proteins (AREA)

Applications Claiming Priority (3)

Publications (1)

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• 1992
  • 1992-08-13 EP EP92917699A patent/EP0600974A1/de not_active Withdrawn
  • 1992-08-13 SK SK179-94A patent/SK17994A3/sk unknown
  • 1992-08-13 HU HU9400420A patent/HU9400420D0/hu unknown
  • 1992-08-13 JP JP5504098A patent/JPH08506796A/ja active Pending
  • 1992-08-13 RU RU94027699/14A patent/RU94027699A/ru unknown
  • 1992-08-13 WO PCT/EP1992/001859 patent/WO1993003746A1/en not_active Ceased
  • 1992-08-13 CZ CS94301A patent/CZ30194A3/cs unknown
  • 1992-08-13 CA CA002115270A patent/CA2115270A1/en not_active Abandoned
  • 1992-09-25 HR HR920488A patent/HRP920488A2/hr not_active Application Discontinuation
• 1994
  • 1994-03-01 BG BG98628A patent/BG98628A/xx unknown

Non-Patent Citations (1)

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