JPS59161315A - Remedy for hepatic disease - Google Patents

Abstract

PURPOSE:The titled remedy containing noscapine or its salt as an active ingredient. CONSTITUTION:A remedy for hepatic diseases containing noscapine {e.g., (s)-6,7- dimethoxy-3-[5, 6, 7, 8-tetrahydro-4-methoxy-6-methyl-1,3-dioxolo[ 4,5-g ]isoquinoline-5-yl)-1(3H)-isobenzofuranone, etc.} or its salt as an active ingredient. Administration may be carried out by parenteral medication such as hypodermic injection, intravenous injection, intramuscular injection, intra-abdominal injection, etc. and also by oral medication. A dose is 0.1-100mg/kg weight/day, once or more times. In the case of oral medication, the remedy is used in the form of tablet, capsule, powder, elixir, etc. Noscapine can be isolated and prepared from a water-soluble residue during opium treatment for producing morphine, it is known as an antitussive, and can be also used as an agent for recovering liver function and an agent for stimulating it.

Description

[Detailed description of the invention] The present invention relates to a therapeutic agent for liver diseases.

No5capine is known as an antitussive. The present inventors found that noscapine is effective as a therapeutic agent for liver diseases, and arrived at the present invention.In other words, the gist of the present invention is to provide a therapeutic agent for liver diseases containing noscapine or a salt thereof as an active ingredient. It is in.

The present invention will be explained in detail below.

First, as noskabine in the present invention, (++)
-4,? -dimethoxy-3-(j?, 57.g-tetrahydroder-methoxy-6-methyl-l,3-dioquine[q,s-g]inquinolin-5-yl)-/(3,
H)-isobenzofuranone and 70di monomer (dl-noskabine, i.e. gutscopine).

In addition, its salts include pharmaceutically acceptable salts, such as inorganic acid salts such as hydrochloric acid, sulfuric acid, phosphoric acid, and nitric acid, or organic acid salts such as acetic acid, succinic acid, propionic acid, oxalic acid, and adipic acid. Can be mentioned.

Noskabine according to the invention can be produced by a conventional method. That is, morphine Ch1m, Phys
, [u]k, 27, (/g/7)).

The liver disease therapeutic agent according to the present invention promotes the regeneration or new generation of liver parenchymal cells when the number or function of hepatic parenchymal cells decreases due to liver diseases such as acute hepatitis and chronic hepatitis, and in rare cases of drugs, and restores the original liver function. It is a liver function restoring agent or liver function stimulant for the purpose of restoring liver disease, and is useful as a therapeutic agent for liver diseases in humans and animals.

Although the therapeutic agent for liver disease according to the present invention can be administered by any method, preferred VC is administered by the following method.

That is, parenteral administration such as subcutaneous injection, intravenous injection, intramuscular injection, and intraperitoneal injection, as well as oral administration are possible.

The dosage depends on the patient's age, physical condition, body weight, type of concurrent treatment, degree of treatment, nature of desired effect, etc.
J: It's decided.

Generally, the 7-day dosage of the active ingredient is 0/~ioθ■/k
ti weight, normal/~,? Ortrino/ky is one body weight and is administered in one or more doses.

For oral administration, it is used in the form of tablets, capsules, powders, elixirs, etc., and for parenteral administration, it is used in sterilized liquid forms such as liquids or suspensions. When used in the forms described above, solid or liquid non-toxic pharmaceutical carriers can be included in the composition.

As an example of a solid carrier, a conventional Ceratin type capsule is used. The active ingredient may also be packaged as a tablet or powder, with or without adjuvants.

These capsules, tablets, and powders generally left ~9%,
Preferably it contains 25-9θ% active ingredient by weight.

i.e., for these modes of administration, 3 to so m9;
Preferably, it contains 2 & -2507% of active ingredient.

As the liquid carrier, water or petroleum, animal, vegetable, riverine, or synthetic oils such as peanut oil, soybean oil, mineral oil, and sesame oil are used.

Generally, physiological saline, dextrose or similar sucrose solutions, and glycols such as ethylene glycol, globylene glycol, and polyethylene glycol are preferred as liquid carriers, and in particular, in the case of injections using physiological saline, it is usually ~, 20%, preferably /-/ 0
% of active ingredient by weight.

For liquid preparations for oral administration, 0. & -/ Suspensions or syrups containing 0% active ingredient by weight are preferred.

As carriers in this case, use aqueous excipients such as perfumes, syrups, pharmaceutical micelles, etc.

Hereinafter, the invention will be further explained with reference to Examples.

Example 1 / Effect on acute liver injury accompanied by centrilobular necrosis (hepatitis model after 7 administrations of carbon tetrachloride) Administered carbon tetrachloride undergoes vicarious training by liver microsomal drug fermentation. Generates trichlor radical. These radicals damage the liver cells, cystic membranes, mitochondrial membranes, and microsome membranes, causing loss of the original functions of hepatocytes and causing centrilobular necrosis. When hepatocytes are damaged in this way, enzyme activity occurs in the VC, and various enzyme activities appear in the serum. Therefore, it is an appropriate method to measure serum transaminase activity as an indicator of the disorder. Serum transaminases include GOT (glutamine-oxaloacetate transaminase) and GPT (glutamine-pyruvic transaminase), and both enzyme activities were measured as indicators of liver damage.

Unfortunately, carbon tetrachloride severely damages the bile canalicular side of liver cells, resulting in bilirubin leaking into the blood. Therefore, determining the blood bilirubin level can be an indicator for investigating hepatocyte damage.

Namely, rat (wistar male, weight around 7502)
VC Liver disease therapeutic agent according to the present invention 2 left! io, / 00
#+97 kl, -C-p days oral administration. Three hours after administering the test compound to Sun and Moon, 0.0. ,z 3 ml/k,y (9 with olive oil
After 2 hours, the blood was collected from the vena cava and centrifuged (3000
Rotate for 10 minutes) to obtain serum, COT in serum,
GPT was measured and activity was expressed according to the International Unit System. The results are shown in Table 7. At the same time, the bilirubin level was also measured and the O

Claims (1)

[Claims] ill A liver disease therapeutic agent containing noscapine or its salt as an active ingredient.