JPS63222119A - Drug for liver disease - Google Patents

Abstract

PURPOSE:To obtain the titled preparation comprising an extract of Myricae cortex (dried bark of Myrica rubra SIEB et Zucc) with an organic solvent. CONSTITUTION:A drug for liver disease containing essence, obtained by extracting Myricae cortex (dried bark of Myrica rubra SIEB et Zucc) with an organic solvent such as methanol, as an active ingredient. Both oral and parenteral administrations are used and the oral administration is preferably. Granule, fine granule, tablet, troche, capsule and pill may be cited as the dosage form. A dose is 50-5,000mg/day, preferably 10-500mg/day and administered one time-several times. The preparation is hardly judged to have toxicity as nontoxicity is understood from the fact that the preparation has been used as a crude drug. The preparation has protecting effects on liver disorder of rat by carbon tetrachloride and alpha-naphthyl isocyanate and is effective against liver diseases.

Description

[Detailed description of the invention] "Industrial application field" TECHNICAL FIELD The present invention relates to a drug for liver diseases.

“Prior Art” Conventionally, as a drug for treating and preventing liver diseases in humans,
Various things have been devised. However, many of these conventional drugs have strong side effects, which poses some practical difficulties. Therefore, a drug for liver diseases with fewer side effects is desired.

"Essentials of the Invention" The present inventors have discovered that extracts of Yang Mei Peel, which is used in herbal medicine, are effective in the prevention and treatment of liver diseases.

That is, the present invention relates to a drug for liver diseases comprising an organic solvent extract of Yang Mei Peel.

Myrioas cortex (Myrioas cortex)
It is the dried bark of the tree ZuaOS + 'T%% family), and has traditionally been used for astringent, hemostatic, and hemostasis, and also for bruises,
It is used externally as a poultice for sprains by mixing it with egg white. It is also used as an insecticide, but it is unclear whether it is effective in preventing or treating liver diseases.
Tannin-related compounds such as millikanol, millicanon, myrica/-luglufuside, millicanol 6'-0-gallol glycoside, tarax-heptadol, taraxerone, myricasiol, etc. have been reported, but whether any of them are effective for the prevention and treatment of liver diseases? has not been reported.

The present invention is based on the new knowledge that components of Yangmei peel extracted with an organic solvent are effective in preventing and curing liver diseases.

The active ingredient of the drug of the present invention is obtained by extracting Yang Mei Peel with an organic solvent. Various methods can be used for the extraction, but for example, it is also possible to extract with methanol and concentrate the extract to obtain an extract. However, for further purification, there are, for example, the following methods. That is, the S* bark is powdered and extracted with benzene, the benzene extract is extracted with an aqueous sodium lignification solution, the extract is made acidic, and then extracted with benzene. The extraction residue is extracted with ethyl acetate, and the resulting residue is extracted with methanol. Boiling water was added to the extract to dissolve the solution, which was then applied to a column such as Mammography (1) (Amberley) XAD-4) and eluted with water and methanol. Column chromatography (II) (Amberlite
AD-2) and elute with water and methanol. By concentrating the methanol elution fractions of column chromatography (1) and ((conversion)), the desired active ingredient can be obtained. The two active ingredients of the drug of the present invention are both brown powders and are tasteless and odorless. , soluble in water, slightly soluble in ethanol. Hygroscopic but not deliquescent. The component obtained by column chromatography (1) shows maximum absorption in the ultraviolet region at wavelengths of 209.265 and 350 nm; The components obtained by are at wavelengths 209 and 2'
It shows maximum absorption at 72 nm.

The drug of the present invention can be administered orally or parenterally, but oral administration is preferred. Examples of oral dosage forms include conventionally used dosage forms such as powder, granules, fine granules, tablets, troches, capsules, and pills.

Examples of parenteral dosage forms include conventionally used dosage forms such as injections and suppositories. Conventional methods are used to manufacture these dosage forms. For example, in the production of tablets, at least one of the compounds of formulas (1) and (2) described above is added with additives conventionally used and thoroughly mixed. Examples of additives include excipients such as corn starch, wheat starch, potato starch, lactose, glucose, mannitol, calcium chloride, calcium sulfate, etc.; binders such as starches, dextrin, gum arabic, tragacanth, sodium alginate, gelatin, and methylcellulose. , ethyl cellulose, polyvinylpyrrolidone, polyvinyl alcohol, etc.; Disintegrants, such as starches, polyvinylpyrrolidone, crystalline cellulose, etc.; Lubricants, such as magnesium stearate, talc; Coloring agents, fragrances, etc. The resulting mixture is granulated using a wet or dry method, or is compressed into tablets using a tablet machine without granulation.

The amount of active ingredient in the tablet may be arbitrary.

When administering the drug of the present invention, for adults, the total amount of the active ingredient should be 50 to 5,000 times a day, depending on the symptoms.
mg, preferably 100 to 500 mg is used.

The compound used in the drug of the present invention has almost no toxicity, as can be seen from the fact that it has been widely used as a crude drug.

As can be seen from the following experimental results, the drug of the present invention is suitable for rat carbon tetrachloride and Sina 7-tyl isothiocyaner) (A
It has a protective effect against liver damage caused by NCT) and is effective against liver diseases.

"Example" Next, reference examples and examples will be shown.

Reference Example (Production of Active Ingredients) Commercially available Yang Mei Peel (4 pieces) was powdered and extracted with benzene (3Q) under reflux four times for 3 hours each. The residue after the benzene extraction was extracted with ethyl acetate (3Q) four times for 3 hours each under reflux.

The residue was extracted with methanol (39) under reflux four times for 3 hours each. The methanol extracts were combined and concentrated under reduced pressure to obtain a methanol fraction (22 g of 1 O).

Both obtained parts were dissolved in boiling water (5 L), and the soluble part was applied to an Amberlite XAD-4 column (6.5 x 50 cm).
A water-eluted portion and a methanol-eluted portion were obtained.

The methanol eluted fraction was concentrated under reduced pressure to obtain a methanol eluted fraction (153 g) as a brown powder (hereinafter referred to as 0-3).
The obtained component is a colored powder, tasteless and odorless, soluble in water, and slightly soluble in ethanol. Although hygroscopic, it does not deliquesce. It showed maximum absorption in the ultraviolet region at wavelengths of 209.265 and 350 nm.

On the other hand, (1) further amber-ray the above-mentioned water elution part) XA
The mixture was passed through a D-2 column (7 x 50 am) to obtain a water eluted portion and a methanol eluted portion. The methanol eluted fraction was concentrated under reduced pressure to obtain a brown powder methanol eluted fraction (7.2 g) (hereinafter referred to as D-2). The obtained component was a colored powder, tasteless and odorless. Soluble in water, slightly soluble in ethanol. Although hygroscopic, it does not deliquesce. It showed maximum absorption in the ultraviolet region at wavelengths of 209 and 272 nm.

Example 1 Active ingredients
5゜Carboxymethylcellulose sodium
140 liters

Five tablets each of the 40 active ingredients and additives were weighed out and mixed uniformly. One tablet was weighed out from the mixture and directly compressed using a key press at a pressure of 20 ok/all'' to obtain a tablet.

The tablets contained 5 Qmg of active ingredient per tablet.

"effect" 1 shows the protective effect of the drug of the present invention on liver parenchymal damage.

Experimental animals Wistar male rats were preliminarily reared for 4 days and then aged 7 days.
Animals with a week-old age and body weight of 200±lQg were selected and used in groups of 5. Feed and water were available ad libitum.

Creation of liver damage model Acts (manufactured by Wako Pure Chemical Industries, Ltd.) was diluted to 20% with olive oil, and 0.3 mQ/200g (a J40.3m117
kg) was injected intraperitoneally into rats fasted for 24 hours. AN Engineering T [Aldrich, Chemical, Company (Aldrich Chemical Com
Pany) is a 75mg/- olive oil solution, and 0
．． 2m+! /200g was injected intraperitoneally.

Preparation and Administration of Samples The samples were suspended in a 5% T'wesn 80 aqueous solution, exposed to ultrasound for 15 minutes, and then intraperitoneally injected once before treatment with the inducing agent.

24 hours after Call + treatment or ANN treatment, the rats were opened under ether anesthesia and blood was collected from the abdominal descending vena cava.
Serum was obtained. Serum components were measured using an automatic biochemical analyzer (Toshiba Medical TEA-380) using GO and GPT.
SAlp.

LDHSIIAP, T-1ail, and 2)il were performed.

Indication of protective efficacy: Each group has 5 rats, and the untreated normal group, the disordered group treated with 0ci4 or ANCT, and the sample administration and disorder combination (sample + disorder) were treated with disorder. Serum components were measured 24 hours later, and the protective efficacy was calculated using the average value of each group according to the following formula.

Impaired group - normal group The measurement results were determined by Student's test to determine whether there was an effect or not.

The results are shown in Table 1.

Ni Ni Ni-4- Heat: p<0.01, ◆: p<0.05 Next, the cholestasis protective effect is shown.

Creation of cholestasis model Dissolve AN-T in olive oil to a concentration of 75 mg/+J, and add 0.2J/200g (75++
+g/kg) was injected intraperitoneally into rats.

Preparation and administration of samples The same procedures as in the hepatic parenchymal injury protective efficacy test were carried out. Bile collection and measurement of bile flow rate 24 hours after AN engineering T treatment, rats were treated with 10% urethane.
Anesthetized by subcutaneous injection of 0 g/kg, the abdomen was opened along the midline of the abdominal wall, and a polyethylene tube (0.9 x 150 mm
) was fixed in the common bile duct.

To eliminate the influence of the surgery, bile was allowed to flow naturally for 20 minutes, and then bile flowing out for 120 minutes was collected. The volume of the collected bile was measured and corrected to the bile weight per g, which was defined as the bile flow rate.

After diluting 10 μl of bile collected 120 minutes after the start of collection with purified water, the concentration of total bile acids was measured by enzymatic colorimetry using an automatic biochemical analyzer, taking bile flow rate into account. The amount of bile acid excreted was calculated.

The average of the measured values was calculated for the disordered group by ANUT, the group to which the sample was administered before administering ANUT (sample + disorder), and the untreated normal group, and the protective efficacy of the sample (4) was determined according to the following formula.
was calculated.

Normal group-disordered group The measurement results were determined by Stenny Punt's t-test to determine whether there was an effect or not.

The results are shown in Table 2 below.0 Table 2: P(0,01+:P(0,05) Liver damage can be caused by many factors, including viral infections, immune disorders, and drugs. However, its pathological conditions are mainly divided into hepatic parenchymal disorder and cholestasis.

Claims (1)

[Claims] Drug for liver diseases made from organic solvent extract of Yang Mei Peel