Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
  • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
• • 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
• • 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
  • A61P13/00—Drugs for disorders of the urinary system
  • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P15/00—Drugs for genital or sexual disorders; Contraceptives

Definitions

• R 1 is hydrogen or alkyl having 1-10 C atoms
• W is a free or functionally modified hydroxyl group on the hydroxyl group, the OH group being fixed or ß-permanent, X is a CH 2 group or an oxygen atom, Z is hydrogen or a cyano group,
• D is a straight-chain or branched saturated alkylene group with 1-5 C atoms
• E is a -C ⁇ C bond or a direct bond
• R 2 is a straight or branched chain, saturated alkyl group with 1-7 C atoms
• R 3 is a free or functionally modified hydroxy group
• R 1 has the meaning of a hydrogen atom, the salts of which with physiologically compatible bases mean, also have a cytoprotective effect in the liver, in the pancreas and in the kidney.
• the alkyl group R 1 is straight or branched alkyl groups with 1-10 C atoms, such as methyl, ethyl, propyl, butyl, isobutyl, tert-butyl, pentyl, neopentyl, heptyl, hexyl, decyl.
• the alkyl groups R 1 can optionally be substituted by halogen atoms, C 1 -C 2 alkoxy groups, phenyl or (C 1 -C 2 ) dialkylamines.
• the hydroxyl groups R 3 and in W can be functionally modified, for example by etherification or esterification, the free or modified hydroxyl groups in W being ⁇ , with free hydroxyl groups being preferred.
• the radicals known to the person skilled in the art are suitable as ether and acyl radicals. Easily removable ether residues such as, for example, the tetrahydropyranyl, tetrahydrofuranyl, ⁇ -ethoxyethyl, trimethylsilyl, dimethyl-tert.butylsilyl and tribenzylsilyl residue are preferred. Examples of possible acyclic residues are: acetyi, propionyl, butyryl, benzoyl.
• the dose of the compounds is 1-1500 ⁇ g / kg / day when administered to the human patient.
• the unit dose for the pharmaceutically acceptable carrier is 0.01100 mg.
• the dosage of IV administration as a continuous infusion in common aqueous solvents e.g. 0.9% NaCl solution, preferably in doses between 0.1 ng / kg / min and 0.1 ⁇ g / kg / min.
• the invention thus also relates to medicaments based on the compounds of the general formula I and customary auxiliaries and carriers.
• pancreatic juice 0.5 jug / kg / min
• pancreatic juice 0.5 jug / kg / min
• the activity of all the steps involved in this process from protein synthesis in the pancreatic cells via intracellular transport of the enzymes formed up to their apical secretion in the lumens of the pancreatic lobes (acini) connected to the pancreatic duct system, pathological changes occur when higher doses are administered (5 ⁇ g / kg / min).
• Pancreatic secretion decreases drastically, the organ swells due to water retention between the cells (interstitial3 edema), the enzymes formed are no longer released into the duct system, but to the side into the interstitial space, or collect in large cabbages (vacuoles) the cells themselves (Dig.Dis.Sci. 27: 993-1002,1982).
• fat necrosis is found in the pancreas and a pronounced cellular inflammatory reaction.
• Table 1 shows the results of this experiment, in which the amylase activity in the serum is measured and given in units / liter (U / l), as well as the vacuolization of the e-cells of the exocrine pancreas, the occurrence of ascites and the enlargement of the pancreas was assessed by an interstitial edema by a score.
• liver cells of the rat were used, which were poisoned with carbon tetrachloride (CCl 4 ) to produce a defined cell damage.
• Cl 4 carbon tetrachloride
• Three different parameters were used to determine the cell damage: 1. Assessment of the cell morphology in a light microscope; 2. absorption of the dye trypah blue, a substance that selectively accumulates in dead cells; 3. Release of cytoplasmic enzymes into the surrounding medium due to destruction of the cell membrane; the activity of lactate dehydrogenase (LDH) was measured.
• LDH lactate dehydrogenase
• Figure 4 shows the result of a representative experiment.
• the addition of CCl 4 causes an approximately 8-fold increase in the trypan blue index; this increase can largely be prevented by adding iloprost.
• the cytoprotective doses are in the range of 0.005 - 0.2 ng / ml.

Landscapes

• Health & Medical Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• Veterinary Medicine (AREA)
• Chemical & Material Sciences (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Medicinal Chemistry (AREA)
• Animal Behavior & Ethology (AREA)
• Life Sciences & Earth Sciences (AREA)
• General Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Engineering & Computer Science (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Epidemiology (AREA)
• Reproductive Health (AREA)
• Endocrinology (AREA)
• Urology & Nephrology (AREA)
• Gastroenterology & Hepatology (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

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Publications (1)

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Cited By (6)

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Citations (3)

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• 1984
  • 1984-07-25 DE DE3448257A patent/DE3448257C2/de not_active Expired
  • 1984-07-25 DE DE19843427797 patent/DE3427797A1/de active Granted
• 1985
  • 1985-07-18 JP JP60503369A patent/JPH0649649B2/ja not_active Expired - Lifetime
  • 1985-07-18 EP EP85903809A patent/EP0191792B1/de not_active Expired - Lifetime
  • 1985-07-18 DE DE8585903809T patent/DE3585282D1/de not_active Expired - Lifetime
  • 1985-07-18 WO PCT/DE1985/000245 patent/WO1986000808A1/de not_active Ceased
• 1989
  • 1989-02-27 US US07/315,878 patent/US5049582A/en not_active Expired - Fee Related

Patent Citations (3)

Non-Patent Citations (3)

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