JP2821575B2 - Liver disorder improving agent - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to an agent for improving liver damage containing an extract of swirling flowers, an extract of white rose or berberine as an active ingredient.

[Prior art and problems] In general, liver injury can be roughly classified into acute hepatitis due to transient infection of the virus, chronic hepatitis due to persistent infection, and cirrhosis, which is said to progress from chronic hepatitis.

In Asian countries, 80-90% of hepatocellular carcinomas occur in patients with cirrhosis, and in the treatment of liver damage, it is necessary to stop this progression somewhere, but in modern medicine, There is no known cure. However, it has recently been reported that a Chinese herbal medicine, Sho-saiko-to, prevents the process from liver cirrhosis to hepatocellular carcinoma, and the development of a therapeutic agent for liver damage from Chinese herbal medicine was expected.

[Means for Solving the Problems] The present inventors have conducted intensive studies on various Japanese and Chinese crude drugs in order to find a more effective drug for treating hepatitis.
The present inventors have found that the extract of swirling flowers, the extract of white rose and berberine have an effect of improving liver damage, thereby completing the present invention.

That is, the present invention provides an agent for improving liver injury containing an extract of swirling flowers, an extract of white rose or berberine as an active ingredient (hereinafter, referred to as a hepatic disorder improving agent).
It is referred to as the drug of the present invention. ).

Whirling flower, Baiwei, is a crude drug that has been used in Chinese herbal prescriptions since ancient times. Whirlpool flowers are known to have an antibacterial effect, white roses have an antitussive effect, and berberine has a stomach and anti-peptic ulcer effect. That is.

An extract of swirling flowers or an extract of white rose can be obtained, for example, as follows.

It can be obtained by extracting swirled flowers or white roses with water and / or an organic solvent and distilling off the extraction solvent from the extract.

Specific examples of organic solvents include methanol, ethanol,
Acetone, hexane, petroleum ether, benzene and the like can be mentioned, and warm extraction is preferable for extraction. The filtrate of the extract can be separated by a method such as decantation or centrifugation.

The extraction solvent is preferably distilled off under reduced pressure and dried.

As berberine, those commercially available from Wako Pure Chemical Industries, Ltd. or the like can be used, and those obtained by appropriately chemically treating to form a salt can also be used.

Berberine having a lower alkyl group (methyl group, ethyl group, propyl group, etc.) introduced at position 13 can also be used. In this case, the lower alkyl group can be introduced by general alkylation.

A specific example of the production of a swirling flower or white rose extract is as follows.

Example 1 374.2 g of swirling flower (Uchida Japanese and Chinese medicine) with 3.5 distilled water 6
The mixture was refluxed twice to obtain a water extract. The solvent was concentrated under reduced pressure, and the residue was sufficiently dried to obtain 37.02 g of a swirling flower extract.

Example 2 487.21 g of white rose (Uchida Kazoku Yakuhin) was refluxed six times with 3.5 distilled water to obtain a water extract. The solvent was concentrated under reduced pressure, and the residue was sufficiently dried to obtain 13.81 g of a white rose extract.

[Effects of the Invention] According to the present invention, in the field of liver disease treatment where the emergence of an effective therapeutic agent has long been desired, a significant effect that an epoch-making liver disorder improving agent can be provided can be obtained. Can be

Next, the hepatic disorder improving effect of the drug of the present invention is described with reference to experimental examples.

Experimental Example 200 μg / animal of P. acnes (P. acnes, obtained from Kitasato Institute) was intraperitoneally administered to ICR male mice. Intraperitoneal administration of 4.0 mg / animal extract of white rose was performed each day, and lipopolysaccharide (LP) was administered 7 days after administration of P. acnes.
S) 1 μg was intraperitoneally administered, and the survival rate of the mice 20 hours after LPS administration was determined.

As a control group, 7 days after administration of P. acnes
LPS (1 μg) was intraperitoneally administered, and the survival rate of the mice 20 hours after LPS administration was determined.

 Table 1 shows the results.

As is clear from this, the drug of the present invention has an excellent liver injury improving action.

Next, the dosage and formulation of the active ingredient of the drug of the present invention will be described.

The active ingredient of the drug of the present invention can be administered to animals and humans as it is or together with a conventional pharmaceutical carrier.
The administration form is not particularly limited and may be appropriately selected and used as needed, and may be used as tablets, capsules, granules, fine granules,
Examples include oral preparations such as powders, and parenteral preparations such as injections and suppositories.

In order to achieve the desired effect as an oral preparation, it depends on the age, weight, and degree of the disease of the patient. It is considered appropriate to take the drug in separate doses.

As for berberine, 10 to 300 mg of berberine chloride per day for adults can be taken orally in several divided doses.

Oral preparations are produced by a conventional method using, for example, starch, lactose, sucrose, mannitol, carboxymethylcellulose, corn starch, inorganic salts and the like.

In this type of preparation, in addition to the above-mentioned excipients, a binder,
Disintegrant, surfactant, lubricant, fluidity enhancer, flavoring agent,
Coloring agents, fragrances and the like can be used. Specific examples are as follows.

[Binder] Starch, dextrin, gum arabic powder, gelatin, hydroxypropyl starch, methyl cellulose,
Sodium carboxymethylcellulose, hydroxypropylcellulose, crystalline cellulose, ethylcellulose, polyvinylpyrrolidone, macrogol.

[Disintegrant] Starch, hydroxypropyl starch, sodium carboxymethylcellulose, calcium carboxymethylcellulose, carboxymethylcellulose, low-substituted hydroxypropylcellulose.

[Surfactant] Sodium lauryl sulfate, soybean lecithin, sucrose fatty acid ester, polysorbate 80.

[Lubricant] Talc, wax, hydrogenated vegetable oil, sucrose fatty acid ester, magnesium stearate, calcium stearate, aluminum stearate, polyethylene glycol.

[Fluidity promoter] Light anhydrous silicic acid, dried aluminum hydroxide gel, synthetic aluminum silicate, magnesium silicate.

Next, the present invention will be described specifically with reference to examples, but the present invention is not limited thereto.

Example 1 Corn starch 44 g Crystalline cellulose 40 g Carboxymethyl cellulose calcium 5 g Light anhydrous silicic acid 0.5 g Magnesium stearate 0.5 g Berberine chloride 10 g Total 100 g Tablets of 200 mg were obtained.

Each tablet contains 20 mg of berberine chloride, and 2 to 15 tablets per day for adults are taken in several doses.

Example 2 84.5 g of crystalline cellulose 0.5 g of magnesium stearate 0.5 g of carboxymethyl cellulose calcium 5 g of berberine chloride 10 g in total 100 g According to the above formula, a part of the mixture was uniformly mixed, compression-molded, pulverized, and The mixture was mixed and compression-molded with a tableting machine to obtain a tablet of 200 mg per tablet.

Each tablet contains 20 mg of berberine chloride, and 2 to 15 tablets per day for adults are taken in several doses.

Example 3 Microcrystalline cellulose 34.5 g 10% hydroxypropyl cellulose ethanol solution 50 g Carboxymethyl cellulose calcium 5 g Magnesium stearate 0.5 g Berberine chloride 10 g Total 100 g
The mixture was wetted by a conventional method, granulated by an extrusion granulator, dried and crushed, mixed with each other, and compression-molded with a tableting machine to obtain a tablet of 200 mg per tablet.

Each tablet contains 20 mg of berberine chloride, and 2 to 15 tablets per day for adults are taken in several doses.

Example 4 Corn starch 84 g Magnesium stearate 0.5 g Carboxymethyl cellulose cellulose 5 g Light anhydrous silicic acid 0.5 g Berberine chloride 10 g Total 100 g And sieved to obtain granules.

1 g of this granule contains 100 mg of berberine chloride, and 0.3 to 1 g of an adult is taken several times a day.

Example 5 Microcrystalline cellulose 40 g 10% hydroxypropyl cellulose ethanol solution 50 g Berberine chloride 10 g Total 100 g According to the above-mentioned formulas, were mixed uniformly and kneaded. After granulation by an extrusion granulator, the granules were dried and sieved to obtain granules.

1 g of this granule contains 100 mg of berberine chloride, and 0.3 to 1 g of an adult is taken several times a day.

Example 6 Corn starch 89.5 g Light anhydrous silicic acid 0.5 g Berberine chloride 10 g Total 100 g According to the above-mentioned formula, was mixed uniformly, and 200 mg was filled in No. 2 capsule.

Each capsule contains 20mg of berberine chloride
And take 2-15 capsules daily for adults, divided into several doses.

Example 7 200 g of the extract obtained in Specific Example 1 or 2 was mixed with 89 g of lactose and 1 g of magnesium stearate, and the mixture was tableted with a single-shot tableting machine to form a slug having a diameter of 20 mm and a weight of about 2.3 g. Make a tablet, crush this with an oscillator, sieved,
The mixture was sieved to obtain good granules having 20 to 50 mesh particles.

The granules are taken at a dose of 0.3 to 14.5 g (corresponding to an extract weight of 0.2 to 10 g) three times a day according to the symptoms.

Example 8 200 g of the extract obtained in Example 1 or 2 was mixed with 20 g of microcrystalline cellulose and 5 g of magnesium stearate, and the mixture was tabletted with a single-shot tableting machine to a diameter of 7 mm and a weight of 225.
mg tablets were produced. One tablet contains 200 mg of the extract obtained in Example 1 or 2. As for this tablet, take 2 to 10 tablets 3 times a day according to symptoms.

Continuation of the front page (56) References Liver 22 No. 8 (1981) 46: 1128-52: 1134 (58) Fields investigated (Int. Cl. ⁶ , DB name) A61K 31/435 A61K 31/78 CA ( STN) REGISTRY (STN)

Claims (1)

(57) [Claims] 1. An agent for improving liver damage, comprising an extract of swirling flowers and an extract of white rose as an active ingredient.