JPS58172320A - Antihyperlipemia and its preparation - Google Patents

Abstract

PURPOSE:The titled pharmaceutical preparation for oral administration comprising an extract of a crude drug as an active ingredient. CONSTITUTION:A crude drug (Sappan Lignum, Polygoni Multiflori Radix, or Polygoni Capsidati Rhizoma) is cut into thin pieces, soaked in a polar or nonpolar organic solvent, an active ingredient is extracted, filtered, concentrated (filter under reduced pressure or ultrafiltration), and, if necessary, the organic solvent is distilled away completely, the prepared substance is evaporated to dryness, or lyophilized, subjected to pharmaceutical manufacturing, to give an antihyperlipemia. Sappan Lignum, one of raw materials, is obtained by drying a central material of Caesalpinia, Sappan L., useful for remedying bruise, menoschesis, menoxenia, abdominalgia, etc. as an antiphlogistic, emmenagogue, and analgesic. Polygoni Multiflori Radix is obtained by drying the bulb of Polygonum multiflorum, and its boiled solution is used as a roborant, tonic, antianemics, etc. Polygoni Capsidati Rhizoma is obtained by drying the root and rhizome of Polygonum cuspidatum, useful as a laxative, diuretic, emmenagogue, antitussive, sedative, etc. EFFECT:Easily obtainable, capable of being easily extracted from inexpensive crude drug of raw material and subjected to pharmaceutical manufacturing, and the production cost is low.

Description

[Detailed description of the invention] do.

The present inventor has spent many years searching for substances that have the effect of reducing the amount of cholesterol in the blood, and as a result of screening tests on numerous natural products, mainly extracts from herbal medicines, we have discovered that they have been used medicinally since ancient times. Among the herbal medicines available, we discovered that Sobo, Kashiyu, and Koshokon had antihyperlipidemic effects, which were completely unknown. Completed the invention.

Scientific name: Sappan Li
gnum), Fabaceae] is the dried heartwood of the Japanese soybean tree cultivated in Guangmian, Yunnan, and Taiwan in China.In Chinese medicine, the infused liquid of this plant is used as an anti-inflammatory, meridian, and analgesic for bruises, menopause, and
It is applied to menstrual disorders, abdominal pain, etc.

Scientific name: Polygoni Multi, flori Ra
dix), Polygonaceae] Zeta is a dried tuberous root of the vine that is cultivated in China's Jiangsu and Anan regions, as well as South Korea. In Chinese medicine, a decoction of it is used as a tonic, tonic, blood supplement, and laxative. .

Polygoni Capsidatr (Rhi) [Scientific name: Polygoni Capsidatr, Rhi
zoma), No. 3 in the Polygonaceae family) is the dried root and rhizome of the Polygonaceae family, and is used as a laxative, diuretic, or emmenagogue in Chinese medicine, and is used in folk medicine as an antitussive, sedative, or hemostat to treat hemorrhoids. It is also used for burns.

In Chinese medicine, the active ingredients of these herbal medicines are generally extracted using Moko water, even though there are differences in temperature and temperature. obtained extracts using pz using an organic solvent instead of water and found that these extracts (this new drug':.:l) were effective.

First, the method for producing the antihyperlipidemic agent of the present invention will be explained in detail.

The herbal medicine is cut into small pieces, immersed in a polar or non-polar organic solvent to extract the active ingredients, filtered and concentrated to obtain an extract, which is then made into a formulation by a commonly used method, if necessary.

As herbal medicines, the aforementioned Somu, Heshugarasu, or Kojokon are used.

Methanol, ethanol, etc. can be used as polar organic solvents, and ether, luhexane, etc. can be used as nonpolar organic solvents.

Extraction of active ingredients from crude drugs involves cold soaking or hot soaking.

Concentration is carried out by reduced pressure or ultrafiltration, and if necessary, the organic solvent is completely distilled off to dryness or freeze-dried.

The extract thus obtained is a brown amorphous solid with a characteristic odor and is hygroscopic.

Next, the pharmacological effects and acute toxicity of the antihyperlipidemic agent of the present invention will be explained.

As a pharmacological effect test, Soki of Production Examples 1 to 3 below,
1 liter of an organic solvent extract of Heshugarasu, Hushu root or tablets of Formulation Examples 1 to 3 described below.

Using a considerable amount of the powder crushed in a pot, the preventive effect of fat emulsion-induced hypercholesterolemia and the preventive effect of hypercholesterolemia induced by high-fat feed were tested. In addition, Banmasin Fiprate was used as a comparative drug.

The preventive effect of fat emulsion-induced hypercholesterolemia was demonstrated in a group of 10 male mice of the DD- strain with a body weight of around 231 kg. %, sodium cholate 0.8%, sucrose 42.
5%, water 21.3%) was orally administered at 25.5 ml/kl, and each test drug was orally administered twice, immediately after and 7 hours later, and blood was collected from each patient 24 hours after administration of the fat emulsion. and tested by measuring total cholesterol in serum. The results are shown in Table G below.

Table 1: Preventive effect on fat emulsion-induced hypercholesterolemia As shown in Table 1, extracts from Somu, Heshuwura, and Huzhu root were found to have the effect of lowering serum cholesterol. .

The preventive effect of high putter feed on hypercholesterolemia is
A group of 10 male mice of the dd- strain weighing around 23 fF were fed a high putter diet [)<'1-12%, cholesterol 1.6%, sodium cholate 0.6%, casein 3.5%, sucrose. 73%, powdered feed (Oriental Yeast M
: manufactured by Oriental Yeast Co., Ltd.) 75.0%], and each test drug was orally administered once a day for 10 consecutive days.
Tests were conducted by fasting 10 hours before blood sampling, and after blood sampling, the liver was collected and homogenized, and cholesterol levels in serum and liver were measured. The measurement method for serum was carried out using the C0D-P-chlorophenol coloring method, and for the cholesterol in the liver, a modified Zak-Henly method was used.

The results are shown in Table 2.

As is clear from Table 2, extracts from Somu, Heshouwu, and Hujoban all significantly lowered serum cholesterol levels, but had no effect on liver cholesterol levels. .

According to the findings of the collected livers, there was a tendency for hepatomegaly to be suppressed in all groups treated with the antihyperlipidemic agent of the present invention, and the change in body weight was observed in the case of normal feed intake, except for the case due to fasting for 10 days. No change was observed compared to the group (no treatment group).

Acute toxicity was observed in 4 mice with a body weight of around 209 mm and 10 mm.
Animals were grouped as one group, and mortality was observed for 7 days after oral administration of each test drug, and LD was determined from the number of deaths. It was tested by determining the value. During the observation period, feed and water were provided ad libitum.
D. Values are calculated using the Richfield-Wilcoxon method (Li
tchfield-WilcOxon method)
It was determined by The results are shown in Table 3.

Table 3 Results of Acute Toxicity Test Even when administered at a high dose of 8000'' IP/k), none of the patients in the antihyperlipidemic agent administration group of the present invention died, indicating that acute toxicity was weak.

As mentioned above, the antihyperlipidemic agent of the present invention, which contains extracts obtained from medicinal plants such as Somu, Heshuwura, and Hujoban, as an active ingredient can be orally administered in the dosage form shown in the formulation examples. It exhibits excellent antihyperlipidemic effect and is extremely useful as a new antihyperlipidemic agent for hyperlipidemia, which has become an increasing problem in recent years. In addition, according to the invention of the manufacturing method, it can be easily extracted from raw materials that are easily available and inexpensive.
Since it can be formulated into a formulation, the manufacturing cost is low and it has high industrial applicability.

The present invention will be specifically explained below by showing production examples and formulation examples of the present invention.

Production example 1 Roughly cut Soki 500? 50% methanol (methanol:water = 1:l volume ratio)2. ! After cold soaking in M and leaving for 2 days, it was filtered, and the F solution was concentrated under reduced pressure at 50C or lower to obtain a candy-like concentrate (extract) 57f (this is referred to as ExtIA).

Furthermore, dissolve this substance in a small amount of methanol and get 51! of ether was added, shaken and separated, and the ether extract was concentrated to dryness to obtain dry extract 281 (this was extracted as Ext l B
).

Production Example 2 Coarsely cut Hekubi Karasu 5005' in 50% methanol 2.51
After cooling and leaving for 2 days, it was filtered and the P solution was concentrated under reduced pressure below 50C to obtain candy-like extract 68F (this was Ezt.
2A) Pj□Furthermore, dissolve this in a small amount of methanol and make 5I! of ether was added, shaken and separated, and the ether extract was concentrated to dryness to obtain dry extract 231 (
This is called Ex12B).

Production example 3: 500 roughly cut tiger stick boards? was cooled in 50% methanol 2.51, left for 2 days, filtered, and the F solution was concentrated under reduced pressure below 50c to obtain candy-like extract 771.
). Furthermore, this product was dissolved in a small amount of methanol and 5I! of ether was added, shaken and separated, and the ether extract was concentrated to dryness to obtain dry extract 181 (this will be referred to as Exi 3 B).

Next, a formulation example using the dried extract obtained in the above-mentioned production example will be shown.

Formulation Example I E, rtlB and potato starch are thoroughly mixed, an appropriate amount of water is added and kneaded, granulated using a screen having a mesh size of 1 sIm x 1, and after drying, sized using an A16 mesh sieve. Magnesium stearate is added to and mixed with the granules, and each tablet is made into 350 square tablets using a tablet machine.

An easily soluble film coat may be applied if necessary.

Store away from light.

Formulation example 2 11 The formulation method is the same as Formulation Example 1 (1 tablet: 410~).

Formulation example 3 415' The formulation method is the same as Formulation Example 1 (14xoW9).

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Claims (1)

[Claims] 1) An antihyperlipidemic agent containing an extract of a crude drug as an active ingredient. 2) The antihyperlipidemic agent according to claim 1, wherein the crude drug is Soboku. 3) The antihyperlipidemic agent according to claim 1, wherein the crude drug is Kashiyu. 4) The antihyperlipidemic agent according to claim 1, wherein the crude drug is peppercorns. 5) A method for producing an antihyperlipidemic agent, which comprises immersing a herbal medicine in a polar or non-polar organic solvent and concentrating the obtained extract by filtration to obtain an extract. 6) The method for producing an antihyperlipidemic agent according to claim 5, wherein the crude drug is Soboku. 7) The method for producing an antihyperlipidemic agent according to claim 5, wherein the crude drug is Kashiyuu. 8) The method for producing an antihyperlipidemic agent according to claim 5, wherein the crude drug is peppercorns.