Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1994-03-02
1996-02-20
Wityshyn, Michael G.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 21, 514838, 530399, A61K 3827, C07K 1461
Patent
active
054928915
DESCRIPTION:
BRIEF SUMMARY
The present invention concerns a method for treatment of patients with chronic liver disease and an agent for use in the method.
The frequency of patients with chronic liver diseases is unknown, but in Europe the number of patients with newly recognized liver diseases seems to be increasing concurrently with the increasing consumption of alcohol.
The chronic liver diseases includes the alcoholic liver cirrhosis, which is dominating in number, liver cirrhosis caused by chronic infection after acute inflammation of the liver and last and more seldom occurring immunological liver diseases characterized by chronic inflammation without known reason.
Especially the alcoholic liver cirrhosis constitutes today a still increasing problem in national health care. The primary treatment available is of preventing character such as abstinence from alcohol in order to prevent aggravation of the disease. Once the alcoholic liver cirrhosis has taken place the present possibilities of therapeutic treatments are very limited.
Normally the alcoholic liver cirrhosis develops gradually and is often preceded by several years of alcoholic abuse. The development of cirrhosis hepatis is preceded by a state of increasing accumulation of fat in the liver (steatosis hepatis). This state is reversible and the liver can be normalised if consumption of alcohol is terminated. However, if the abuse goes on then the liver tissue will gradually be transformed to connective tissue which leads to badly working liver tissue and consequently reduced function of the liver.
Under normal conditions the liver plays an important role in metabolism including accumulation of nutrients, transformation and excretion of waste products, production of proteins which are important for the composition and coagulation of the blood. Furthermore, the liver functions as a gland by producing and secreting gall as well as various hormones comprising IGF-1. In case of reduced function of the liver all this above mentioned functions are influenced in various degrees and the patient with chronic liver disease is especially characterized by having in the blood very low concentrations of the proteins and hormones which are produced in the liver. A reduced concentration of the protein albumin in the blood is of importance for the development of edema in the abdominal cavity such as ascites and in the legs, which problems are often connected with patients having a chronic liver disease. A reduced capability of production of coagulation factors, which are important for the normal coagulation of blood, leads to an increased tendency of bleeding in these patients and this tendency is used to express the degree of failure of the liver.
Patients having a chronic liver disease are furthermore characterized by having a distorted regulation of a number of endocrine systems. As one result among others, is the ascertainment of greatly reduced concentrations of the growth factor IGF-1 (Insulin-like Growth Factor-1) in the blood. IGF-1 is a hormone which is mainly produced in the liver upon stimulation by GH (Growth Hormone) from the pituitary gland. IGF-1 plays an important role for the growth and development of children. Further IGF-1 is important for metabolism by stimulation of protein synthesis in the liver and other organs, besides it is important for regulation of the carbohydrate metabolism. IGF-1 is synthesized and released from the liver caused by GH stimulation, and children with GH-deficiency are characterized by having very low concentrations of IGF-1 in the blood.
When a chronic liver disease has reached the state of incipient failure of the liver then the capability of the liver to produce IGF-1 is reduced and therefore very low concentrations of IGF-1 is found in the blood. It appears that there is a positive correlation between the reduction in IGF-1, the degree of the liver disease and the prognosis of the patients. As a physiological reaction to the above mentioned conditions increased basic GH concentrations are found in the blood of these patients. However, thes
REFERENCES:
patent: 4898857 (1990-02-01), Aroonsakul
Giordano et al. "Somatomedin (Sm) Behavior In Patients With Chronic Liver Diseases" Acta Endocrin. Suppl. 199 262 1975.
Moller et al. "Effect of Recombinant Human Growth Hormone (rHGH) on Insulin-Like Growth Factor (IGF-1) In Patients w/Cirrhosis of The Liver" J. Hepatol 13(Suppl 2) S146 1991.
Schimpff et al. "Serum Somatomedin Activity Measured As Sulphation Factor In Peripheral, Hepatic & Renal Veins of Patients with Alcoholic Cirrhosis" Acta Endocrin. 88(4) 729-736 1978.
Schimpff et al. "Somatomedin Production In Normal Adults & Cirrhotic Patients" Acta Endocrin 86(2) 355-362 1977.
Eversmann et al. "Somatomedin-B In Acromepoly, Liver Cirrhosis, & Renal Failure" Acta Endocrin Suppl. 212 p. 186 Abstract #320 1977.
Moeller Soren
Skakkeb k Niels E.
Agris Cheryl H.
Degen Nancy J.
Novo Nordisk A S
Wityshyn Michael G.
Zelson Steve T.
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