JPH06135847A - Gallstone formation inhibitor - Google Patents

Abstract

PURPOSE:To provide a medicine low in side effects and useful as an excellent medicine for prevention or improvement of gallstone diseases. CONSTITUTION:This gallstone formation inhibitor contains SHOSAIKOTO (kind of Chinese medicine) exhibiting an anti-inflammatory effect, a cell membrane stabilization effect, an anti-allergic effect, an immunological enhancement effect, etc., and, therefore, used for improving various kinds of chronic hepatic diseases as the active component. SHOSAIKOTO contains Bupleuri radix, Pinelliae tuber, Scutellariae radix, Zizyphi fructus, ginseng, Glycyrrhizae radix and Zingiberis rhizoma respectively in a ratio within a range of 4.0 to 7.0, 4.0 to 5.0, 3.0, 2.0 to 3.0, 2.0 to 3.0, 4.0 and 1.0 to 4.0. SHOSAIKOTO is used for preparation without any modification or in the form of an extract, preferably an aqueous extract in combination with a known medical carrier. This inhibitor has a remarkable inhibition effect on biliary hypertrophy or gallstone formation in the liver or the bile duct. As the suitable dosage, 3 to 15g/day per adult is administrated in several times a day.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a drug having few side effects and useful as a preventive and therapeutic drug for cholelithiasis.

[0002]

2. Description of the Related Art At present, gallstone-dissolving agents represented by bile acids such as ursodeoxycholic acid and chenodeoxycholic acid are widely used as therapeutic agents for cholelithiasis. However, these conventional gallstone lytic drugs are associated with diarrhea, nausea,
Side effects such as liver dysfunction have been confirmed, and it is necessary to pay close attention to the application criteria.

Therefore, it has been desired to develop a more effective drug for preventing and treating cholelithiasis with less side effects.

[0004]

Means for Solving the Problems In order to solve the above problems, the present inventors have conducted diligent research on various Kampo prescriptions, and as a result, Sho-saiko-to causes common bile duct hypertrophy and intrahepatic / intraductal stone formation. They have found that they have a markedly suppressing effect, and have completed the present invention.

That is, the present invention is a gallstone formation inhibitor containing Shosaikoto as an active ingredient (hereinafter referred to as the agent of the present invention).

Sho-saiko-to, which is used as an active ingredient of the drug of the present invention, is a herbal medicine containing crude drugs such as saiko, half-summer, orange, jujube, ginseng, licorice and ginger. It is used for the treatment of various chronic liver diseases due to its stabilizing action, anti-allergic action, immunostimulatory action and the like.

This Shosaikoto has the following compounding ranges, though there are some differences. Saiko 4.0-7.0 Half-summer 4.0-5.0 Korei 3.0 Otsume 2.0-3.0 Ginseng 2.0-3.0 Licorice 2.0 Ginger 1.0-4 .0

The agent of the present invention may be prepared by formulating Shosaikoto in the above formulation as it is or by using an extract thereof as an active ingredient in combination with a known pharmaceutical carrier.

Examples of Shosaikoto extract include various aqueous solvent extracts of Shosaikoto, and it is preferable to use a water extract.

A specific example of preparation of Shosaikoto extract is a method in which Shosaikoto of the above composition is extracted with 10 times the amount of hot water and the resulting extract is filtered. This extract can be dried if necessary and used as a dry powder.

A specific example of Shosaiko-to will be shown and described in detail.

SPECIFIC EXAMPLE 1 7 g of Saiko, 3 g of yellow sprouts, 2 g of licorice, 3 g of carrots, 1 g of ginger,
Mixed herb medicine of 3 g of Ojutsu and 5 g of half-summer (Kosaikoto: 24 g)
240 g of purified water was added, and the mixture was heated and extracted at 100 ° C. for 1 hour. The obtained extract was filtered and spray-dried to obtain 2.3 g of dry extract powder.

Concrete Example 2 700 g of Saiko, 300 g of yellow sprouts, 200 g of licorice, 30 ginseng
24 g of purified water was added to 0 g, 100 g of ginger, 300 g of Oju, and 500 g of half-summer mixed crude drug (Sho-saiko-to: 2.4 kg), and the mixture was heated and extracted for 1 hour after reaching 100 ° C. The obtained extract was centrifuged and the residue was separated to obtain 20 l of a solution.

This solution was subjected to aseptic clarification filtration with a 0.3 μm membrane filter (manufactured by Toyo Roshi Kaisha, Ltd.). The obtained filtrate was ultrafiltered using a diafilter G-10T (manufactured by Bio Engineering Co., Ltd .: molecular weight cut off 10,000). For this ultrafiltration, a membrane with a diameter of 152 mm was set on the lower surface of a container with an internal volume of 2.0 l and the pressure was 3 kg / cm ^2.
Then, as the liquid in the container was concentrated, about 2 l of purified water was added. As a result, 20 l of ultrafiltrate was obtained.

Next, the experimental examples will be described to explain that the agent of the present invention has a remarkable inhibitory effect on common bile duct hypertrophy and intrahepatic / intraductal stone formation.

Experimental Example The effect of Sho-saiko-to on intra-bile and intra-bile duct stones in rats fed long-term lithocholic acid was examined.

Method of Administering Test Samples 6-week-old Wistar male rats were bred for 36 weeks using a feed according to the following classification, and the effect of Shosaikoto was examined. The rats of group A are also used for studying the action of Shosaikoto in normal rats. Group A: The feed containing Shosaikoto obtained in Example 1 at a concentration of 1% was freely taken. Group B: 2% lithocholic acid-containing feed was freely taken. Group C: A diet containing Shosaikoto obtained in Example 1 was freely taken at a concentration of 1% in a diet containing 2% lithocholic acid.

Measurement After measuring the body weight of the rat, ketamine (50 mg / rat,
i. m. ), And a midline incision was made. Wet liver weight, spleen weight and bile duct width of the dissected rat were measured, and if there was a stone in the bile duct, the weight was also measured. The results are shown in Tables 1 and 2.

Table 1

Table 2

As is clear from the above results, the group administered with the drug of the present invention (group C) is significantly more prominent in bile duct hypertrophy and intrahepatic / intraductal stone formation than the non-administered group (group B). It was confirmed that it has an inhibitory effect on. Therefore, the drug of the present invention is considered to be useful as a gallstone formation inhibitor.

It should be noted that Shosaikoto used as the drug of the present invention has a long history as a Chinese medicine and its safety has been confirmed, so it can be used with confidence. For example, it is extremely safe as it is clear from the fact that no death is observed in the oral administration of 15 g / kg, which is the limit administration, to mice and rats.

Next, the dose and formulation of the drug of the present invention will be described.

The dosage form of the drug of the present invention is not particularly limited and may be appropriately selected and used as needed. Oral preparations such as tablets, capsules, granules, fine granules and powders, injection preparations,
Parenteral agents such as suppositories may be mentioned.

In order to exert the intended effect, it depends on the age, body weight, and degree of disease of the patient, but usually, in adults, the weight of the drug of the present invention is 3 to 15 g divided into several times a day. It seems that it is appropriate to take.

The agents of the present invention include oral agents such as tablets, capsules and granules, such as starch, lactose, sucrose, mannitol, carboxymethyl cellulose, corn starch,
It is produced by a conventional method using inorganic salts and the like.

In addition to the above-mentioned excipients, a binder, a disintegrant, a surfactant, a surfactant, a fluidity promoter, a flavoring agent, a coloring agent, a fragrance, etc. may be appropriately used in this type of formulation. You can
Specific examples of each are as shown below.

[Binder] Starch, dextrin, gum arabic powder, gelatin, hydroxypropyl starch,
Methyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl cellulose, crystalline cellulose, ethyl cellulose, polyvinylpyrrolidone, macrogol.

[Disintegrant] Starch, hydroxypropyl starch, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, carboxymethyl cellulose, low-substituted hydroxypropyl cellulose.

[Surfactant] sodium lauryl sulfate,
Soy lecithin, sucrose fatty acid ester, polysorbate 80.

[Lubricant] Talc, waxes, 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.

The agents of the present invention can also be administered as suspensions, emulsions, syrups and elixirs, and these various dosage forms may contain flavoring agents and coloring agents. Good.

On the other hand, parenteral preparations are manufactured by a conventional method,
Generally, distilled water for injection, physiological saline, aqueous glucose solution, vegetable oil for injection, sesame oil, peanut oil, soybean oil, corn oil, propylene glycol, polyethylene glycol and the like can be used as the diluent. Further, if necessary, a bactericide, a preservative, and a stabilizer may be added. Further, from the viewpoint of stability, this parenteral preparation may be filled in a vial or the like and then frozen, the water content may be removed by a usual freeze-drying technique, and a liquid preparation may be re-prepared from the freeze-dried product immediately before use. Further, an isotonicity agent, a stabilizer, a preservative, a soothing agent and the like may be added as needed.

Next, the present invention will be described in more detail by showing examples of the pharmaceutical preparation of the present invention, but the present invention is not limited thereto.

Example 1 Corn starch 21 g Crystalline cellulose 10 g Carboxymethyl cellulose calcium 7 g Light anhydrous silicic acid 1 g Magnesium stearate 1 g Shosaikoto obtained in Example 1 160 g Total 200 g According to the above formulation, It was compression-molded with a tablet machine to obtain 200 mg tablets. This tablet contains 160 mg of Shosaikoto obtained in Example 1, and 20 to 80 tablets for an adult are divided into several doses and taken.

Example 2 Corn starch 29 g Magnesium stearate 2 g Carboxymethyl cellulose calcium 8 g Light anhydrous silicic acid 1 g Shosaikoto obtained in Example 1 160 g Total 200 g According to the above formulation, the After compression molding, it was crushed by a crusher and sieved to obtain granules. 1g of this granule contains 800mg of Shosaikoto obtained in Example 1, and 4-18g per day for an adult
Take in several divided doses.

Example 3 Corn starch 19 g Light anhydrous silicic acid 1 g Shosaikoto obtained in Example 1 180 g Total 200 g According to the above formulation, the
Was filled in a No. 2 capsule. 20 mg of Shosaikoto obtained in Example 1 is contained in one capsule of this capsule, and 20 to 80 capsules per day for adults are to be taken in several divided doses.

Example 4 To 20 liters of Shosaikoto obtained in Example 2, 300 g of alanine (free of pyrogens) was added, dissolved and lyophilized. This lyophilized product was dispensed into 900 vials to obtain an injection. This injection 1 vial contains lyophilized product 406m
g, and easily dissolved in 10 ml of purified water. In addition, the injectable solution after dissolution had a transmittance of 92% (550 nm) and passed the test method for pyrogenic substances of the Japanese Pharmacopoeia.

Claims (1)

[Claims] 1. A gallstone formation inhibitor containing Shosaikoto as an active ingredient.