JP6935285B2 - Pharmaceutical composition - Google Patents

Description

The present invention relates to a pharmaceutical composition for reducing liver fat. Specifically, the present invention relates to a pharmaceutical composition having an excellent effect of reducing liver fat and suppressing side effects of diarrhea.

In recent years, an increase in obesity has become a major problem due to intake of a high-fat diet and lack of exercise. Obesity is a condition in which fat is excessively accumulated in the body, and is considered to be one of the causes of lifestyle-related diseases such as diabetes, arteriosclerosis, heart disease, stroke, hypertension, and hyperlipidemia. Obesity includes subcutaneous adipose tissue in which fat is excessively accumulated in the subcutaneous tissue at the lower part of the skin, and visceral fat obesity in which excess fat is accumulated around the internal organs such as the mesentery in the abdomen.

There has been extensive research on medicines to improve obesity. For example, bofutsushosan and daisaikoto are known as Chinese herbs that improve obesity. For example, Patent Document 1 discloses an anti-obesity drug that improves the anti-obesity effect of Bofutsusho-san by using bofutsu-shosan in combination with plantain and Moroheiya. Further, for example, Patent Document 2 discloses a pharmaceutical composition having an anti-obesity effect, which comprises bofutsushosan and pantothenic acids. Further, for example, Patent Document 3 discloses an anti-obesity pharmaceutical composition containing daisaikoto and pantothenic acids.

By the way, in the liver, a state such as accumulation of triglyceride and cholesterol occurs. Accumulation of fat in the liver can cause fatty liver, increase the likelihood of developing cirrhosis and liver cancer, and cause various lifestyle-related diseases. However, the mechanism of action of liver fat accumulation is different from that of subcutaneous fat and visceral fat accumulation. Therefore, even a pharmacological component that is effective in reducing subcutaneous fat and visceral fat is not necessarily a pharmacological component that is effective in reducing liver fat. Therefore, in order to reduce liver fat, it is required to develop a method different from the reduction of subcutaneous fat and the like.

Bofutsushosan and daisaikoto, which are conventionally known as pharmaceutical compositions for improving obesity, are known to have a reduction effect on visceral fat and subcutaneous fat, but a satisfactory effect on reduction of liver fat. Not obtained. In addition, Bofutsushosan and daisaikoto both have a high sagging effect, and increasing their content in order to enhance anti-obesity and reducing liver fat, or trying to combine both, has side effects of diarrhea. There was a concern.

Japanese Unexamined Patent Publication No. 11-13586 JP-A-2009-196972 Japanese Unexamined Patent Publication No. 2009-196990

In view of the above situation, it is an object of the present invention to provide a pharmaceutical composition for reducing liver fat, which has an excellent effect of reducing liver fat and suppresses side effects such as diarrhea.

The present inventor conducted diligent research to solve the above problems, and found that the effect of reducing liver fat could be improved by combining Bofutsushosan and daisaikoto. In addition, both Bofutsushosan and daisaikoto are known to have a squatting effect, but by using both, surprisingly, the squatting effect is moderately adjusted and the side effects of diarrhea are suppressed. Found to be done. Furthermore, it was found that the effect of reducing liver fat can be further improved while suppressing the side effects of diarrhea by blending Bofutsushosan and daisaikoto in a specific weight ratio. Furthermore, the present invention has been completed by further studies based on these findings.

That is, the present invention provides the inventions of the following aspects.
Item 1. A pharmaceutical composition for reducing liver fat containing (A) bofutsushosan extract powder and (B) daisaikoto extract powder.
Item 2. Item 2. The pharmaceutical composition for reducing liver fat according to Item 1, which contains 0.05 to 10 parts by weight of the component (B) with respect to 1 part by weight of the component (A).
Item 3. Item 2. The pharmaceutical composition for reducing liver fat according to Item 1 or 2, wherein the daily dose of the component (A) is set to 500 to 10000 mg.
Item 4. Item 3. The pharmaceutical composition for reducing liver fat according to any one of Items 1 to 3, wherein the daily dose of the component (B) is set to 400 to 8000 mg.

According to the present invention, it is possible to provide a pharmaceutical composition for reducing liver fat, which has an excellent effect of reducing liver fat. The pharmaceutical composition for reducing liver fat of the present invention is applied as a drug capable of significantly reducing liver fat and suppressing side effects of diarrhea.

The pharmaceutical composition for reducing liver fat of the present invention is characterized by containing (A) bofutsushosan extract powder and (B) daisaikoto extract powder. Hereinafter, the pharmaceutical composition for reducing liver fat of the present invention will be described in detail.

Pharmaceutical composition for reducing liver fat The pharmaceutical composition for reducing liver fat of the present invention includes (A) bofutsushosan extract powder (hereinafter, also referred to as "(A) component") and (B) Oshiba Koto extract. It is characterized by containing a powder (hereinafter, also referred to as “component (B)”).

(A) Bofutsushosan extract powder The pharmaceutical composition for reducing liver fat of the present invention contains bofutsushosan extract powder. For Bofutsushosan, the Chinese medicine prescription described in "Guide for New General Chinese Medicine Prescription" (supervised by Yukihiro Goda and Takashi Hakamatsuka, edited by Japan Herbal Medicine Association, published by Jiho Co., Ltd.) is preferable. , Sanshishi, Forsythia, Hakka, Shokyo, Schizonepeta, Siler, Maou, Daiou, Byakujutsu, Kikyo, Ogon, Kanzo, Sekou, Kaseki, and Bosho. In addition, as stipulated in the "Basic Handling Policy for Chinese Herbal Preparations" established by the Chinese Herbal Medicine Research Committee, the Chinese herbal prescriptions (herbal medicine formulations) described in the letters related to Chinese herbs that are currently in common use and these Includes extracts obtained from Chinese herbal formulas.

The bofutsushosan extract powder is obtained by concentrating the extract obtained by extracting the crude drug according to the bofutsushosan prescription and drying it to obtain a dry extract powder. The extraction solvent used in the extraction treatment of Bofutsushosan is not particularly limited, and examples thereof include water and hydrous ethanol. The extraction process of Bofutsushosan is not particularly limited, but for example, after extracting with an extraction solvent in an amount of about 20 times the total weight (dry weight equivalent) of the crude drug contained in Bofutsushosan, 1 An example is a method of obtaining a bofutsushosan extract obtained by concentrating until the volume becomes / 2 and removing the solid content (extract). Then, by subjecting this extract to a drying treatment, bofutsushosan extract powder is obtained. The drying treatment is not particularly limited, and a known method may be used. For example, a spray-drying method or a soft extract having an increased concentration of the extract is adsorbed by adding an appropriate adsorbent (for example, silicic anhydride, starch, etc.). Examples include the final method.

In the present invention, the bofutsushosan extract powder may be prepared by the above-mentioned method or may be commercially available. For example, Bofutsushosan Dry Extract A, Bofutsushosan Dry Extract AM, Bofutsushosan Dry Extract E, and Bofutsushosan Dry Extract EM (all manufactured by Nippon Powder Co., Ltd.), and Bofutsushosan Dried extract-C and bofutsushosan dry extract-F (both manufactured by Alps Yakuhin Kogyo Co., Ltd.) are known as commercial products and can be obtained commercially.

The content of the component (A) in the pharmaceutical composition of the present invention is not particularly limited as long as the effects of the present invention are exhibited, but is usually 20 to 95% by weight, preferably 25 to 95% by weight, and more preferably 30 to 95% by weight. By weight%, more preferably 30 to 75% by weight. In the present invention, the amount of the component (A) is an amount excluding the additive when the component (A) contains an additive such as an adsorbent added at the time of production.

(B) Daisaikoto extract powder The pharmaceutical composition for reducing liver fat of the present invention also contains daisaikoto extract powder. For daisaikoto, the Chinese medicine prescription described in the "Guide for New General Chinese Medicine Prescription (supervised by Yukihiro Goda and Takashi Hakamatsuka, edited by the Japan Herbal Medicine Association, published by Jiho Co., Ltd.) is preferable, and psycho, hange, rhubarb, and peony. It is a mixed crude drug consisting of peony, ginger, taiso, and rhubarb.

The daisaikoto extract powder is obtained by concentrating the extract obtained by extracting the crude drug according to the daisaikoto prescription and drying it to obtain a dried extract powder. The extraction solvent used for the extraction treatment of daisaikoto is not particularly limited, and examples thereof include water and hydrous ethanol. The extraction process of daisaikoto is not particularly limited, but for example, after extracting with an extraction solvent in an amount of about 20 times the total weight of crude drugs contained in daisaikoto (in terms of dry weight), 1/2. An example is a method of obtaining a daisaikoto extract obtained by concentrating until the volume is reached and removing the solid content (extract). Then, by subjecting this extract to a drying treatment, daisaikoto extract powder is obtained. The drying treatment is not particularly limited, and a known method may be used. For example, a suitable adsorbent (for example, silicic anhydride, starch, etc.) is added to a soft extract having an increased concentration of the spray-drying method extract to adsorb the powder. And the like.

In the present invention, the daisaikoto extract powder may be prepared by the above-mentioned method or may be commercially available. For example, daisaikoto dried extract, daisaikoto dried extract AM, daisaikoto dried extract SN, daisaikoto dried extract powder (all manufactured by Nippon Powder Co., Ltd.), daisaikoto dried extract F, daisaikoto dried Extract-F (both manufactured by Alps Pharmaceutical Co., Ltd.) and the like are known as commercial products, and can also be obtained commercially.

The content of the component (B) in the pharmaceutical composition of the present invention is not particularly limited as long as the effects of the present invention are exhibited, but is usually 5 to 80% by weight, preferably 5 to 70% by weight, and more preferably 7 to 70% by weight. By weight%, more preferably 10 to 50% by weight. In the present invention, the amount of the component (B) is an amount excluding the additive when the component (B) contains an additive such as an adsorbent added at the time of production.

In the pharmaceutical composition of the present invention, the weight ratio of the component (A) to the component (B) is such that the effect of reducing liver fat is further excellent, and the component (B) is added to 1 part by weight of the component (A). It is usually 0.05 to 10 parts by weight, preferably 0.1 to 5 parts by weight, more preferably 0.25 to 4 parts by weight, still more preferably 0.5 to 3 parts by weight.

Other Ingredients The pharmaceutical composition of the present invention may contain other pharmacological components in addition to the above-mentioned components (A) and (B), if necessary. The type of such pharmacological component is not particularly limited, but for example, an antacid, a stomachic agent, a digestive agent, an intestinal regulator, an antispasmodic agent, a mucosal repair agent, an anti-inflammatory agent, an astringent agent, an antitussive agent, an antitussive agent, an expectorant, and an anti-inflammatory agent. Examples thereof include enzyme preparations, sedative hypnotics, antihistamines, caffeines, cardiotonic diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, crude drugs, crude drug extract powders, vitamins, menthols and the like. These pharmacological components may be used alone or in combination of two or more. Further, the content of these pharmacological components may be appropriately set from known ones according to the type of the pharmacological component to be used and the like.

The pharmaceutical composition of the present invention may contain a pharmaceutically acceptable base, additives and the like, if necessary, in order to prepare the desired dosage form. Such bases and additives include, for example, excipients, binders, disintegrants, lubricants, tonicity agents, plasticizers, dispersants, emulsifiers, solubilizers, wetting agents, stabilizers. Agents, suspending agents, pressure regulators, coating agents, brighteners, water, fats and oils, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, surfactants, metal soaps , Lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, UV inhibitors, preservatives, flavoring agents, fragrances, powders, thickeners, pigments, chelating agents and the like. These bases and additives may be used alone or in combination of two or more. Further, the contents of these bases and additives may be appropriately set from known ones according to the type and dosage form of the additive component to be used.

Dosage Form / Formulation Form / Use The administration form of the pharmaceutical composition of the present invention is not particularly limited, but oral administration (oral administration) is preferable.

The pharmaceutical composition of the present invention may be in a solid state, a semi-solid state, or a liquid state.

Specific formulations of the pharmaceutical composition of the present invention include, for example, capsules (soft capsules, hard capsules), tablets, granules, powders, jellies, liquids and the like. Among these, tablets, granules, powders and liquids are preferable, tablets, granules and powders are more preferable, and tablets and granules are particularly preferable.

The pharmaceutical composition of the present invention is produced by appropriately adding the above-mentioned component (A), component (B), and other additives necessary for obtaining a desired dosage form, and using a method known in the pharmaceutical field. be able to.

The pharmaceutical composition of the present invention has an excellent effect on the reduction of liver fat. Liver fat is distinctly different from subcutaneous fat and visceral fat. Subcutaneous fat and visceral fat are fats accumulated in adipocytes, whereas liver fats are fats that are excessively present in adipose tissue, which is a non-adipose tissue that originally has almost no adipose tissue. .. Visceral fat is formed by the accumulation of excess fat absorbed from the gastrointestinal tract around the mesentery that extends from the intestine, yet the excess fat is carried to the subcutaneous tissue and becomes subcutaneous fat. The reduction of visceral fat and subcutaneous fat requires the breakdown and burning of fat. On the other hand, liver fat is the fat that is carried to the liver by blood and is accumulated without being metabolized by the liver. To reduce liver fat, not only fat decomposition and burning but also the metabolic function of the liver are involved. It has a great direct effect. Therefore, there is no accumulation of subcutaneous fat or visceral fat, and even if the patient is not obese, liver fat may be accumulated, and it cannot be said that there is an inseparable relationship between subcutaneous fat or visceral fat and liver fat. .. Therefore, even if the component is effective in reducing subcutaneous fat and visceral fat, the component is not always effective in reducing liver fat.

The administration target of the pharmaceutical composition of the present invention includes humans who are required to suppress the accumulation of liver fat or reduce the liver fat. The pharmaceutical composition of the present invention is used for the purpose of preventing the accumulation of liver fat or for the purpose of improving the accumulation of liver fat.

The dose of the pharmaceutical composition of the present invention is not particularly limited as long as it has the effect of reducing liver fat and has no side effect of diarrhea, but the daily dose of the component (A) is 500 to 10,000 mg. The daily dose of the component (B) is preferably set to 1000 to 8000 mg, more preferably 2500 to 8000 mg, and the daily dose of the component (B) is set to 400 to 8000 mg, preferably 400 to 5000 mg, more preferably 500 to 4000 mg. In the present invention, the amounts of bofutsushosan extract powder and Oshiba Koto extract powder are added when these extract powders contain additives such as adsorbents added during the production of the extract powders. It is the amount excluding the amount of the agent.

As described above, the pharmaceutical composition for reducing liver fat of the present invention is excellent in the effect of reducing liver fat. In addition, the side effects of diarrhea are suppressed. The pharmaceutical composition for reducing liver fat of the present invention is used for the purpose of preventing the accumulation of liver fat or for the purpose of improving the accumulation of liver fat. In addition, the pharmaceutical composition for reducing liver fat of the present invention can be applied to preventive or therapeutic applications for diseases that may develop due to accumulation of liver fat.

Next, the present invention will be described in more detail by way of examples, but the present invention is not limited to these examples.

Experimental example
1. 1. Preparation of test sample
(1) Bofutsushosan extract powder raw material crude drug, Touki 1.2 (part by weight, same below), Shakuyaku 1.2, Senkyu 1.2, Sanshishi 1.2, Renkyo 1.2, Hacka 1.2, Show 1.2, Keigai 1.2, Bow Fu 1.2, Maou 1.2, Daiou 1.5, Bow Show 1.5, Byakujutsu 2.0, Kikyo 2.0, Ogon 2.0, Kanzo 2.0 , Seckou 2.0, and Casseki 3.0, and after chopping them, extract with 20 times the weight of water (560 parts by weight) at about 100 ° C. for 1 hour, and centrifuge to extract the extract. The mixture was concentrated under reduced pressure and dried using a spray dryer to obtain Bofutsushosan extract powder. The drying with a spray dryer was carried out by dropping the extract onto an atomizer having a rotation speed of 10000 rpm and supplying hot air with air at 150 ° C.

(2) Daisaikoto extract powder raw material crude drug, Psycho 6.0 (part by weight, same below), Hange 4.0, Shokyo 1.0, Ogon 3.0, Shakuyaku 3.0, Taisou 3.0, It was used at a ratio of 2.0 Kijitsu and 1.0 Daiou, and after chopping these, extracted with 20 times the weight of water (460 parts by weight) at about 100 ° C. for 1 hour, and centrifuged to obtain an extract. It was concentrated under reduced pressure and dried using a spray dryer to obtain daisaikoto extract powder. The drying with a spray dryer was carried out by dropping the extract onto an atomizer having a rotation speed of 10000 rpm and supplying hot air with air at 150 ° C.

2. Experimental method SD rat (4 weeks old) males were acclimated to a normal diet (MF feed, manufactured by Oriental Yeast Co., Ltd.) for 1 week (average weight at acclimation: 157 g). The acclimated rats were divided into 4 groups (6): control group (Comparative Example 1), Bofutsushosan group (Comparative Example 2), Oshiba Koto group (Comparative Example 3), and Bofutsushosan / Oshiba Koto group (Example 1). The animals / groups were divided and each group was bred for 21 days on a high-fat feed (high fructose diet "F2HFrD", manufactured by Oriental Yeast Co., Ltd.) shown in Table 1 (during the breeding period, rats were bred). Freed food and water). In addition, during the 21-day breeding, for each group, the compositions obtained by dissolving the bofutsushosan extract powder and the daisaikoto extract powder obtained above in distilled water for injection were obtained with the doses shown in Table 2. It was orally administered once a day at 10 mL per kg of body weight. Distilled water for injection was administered to the control group.
The body weight was measured regularly from the start of breeding on a high-fat feed, a blood test was performed on the 14th and 21st days, and an autopsy was performed on the 21st day to measure the lipid in the liver. The presence or absence of diarrhea during the test period was also observed. The results are shown in Tables 3-6. The numerical values in the table are the average values in each group.

According to Table 3, in the administration of about half the amount of Bofutsushosan and about half the amount of daisaikoto (Example 1), the full dose of Bofutsushosan (Comparative Example 2) and the full administration of Daisaikoto (Comparative Example 3) It was shown that the weight loss effect was improved. In addition, according to Tables 4 and 5, the triglyceride in the blood and the triglyceride in the liver are also windproof as compared with the Bofutsushosan group (Comparative Example 2) and the Oshiba Koto group (Comparative Example 3). The number of Tsushosan and Oshiba Koto groups (Example 1) decreased significantly. In this way, in the Bofutsushosan / daisaikoto group (Example 1), although only about half of the bofutsushosan and daisaikoto were administered, each full dose (bofutsushosan) was administered. It showed a higher liver fat reduction effect than the Tsushosan group and Daisaikoto group) (Comparative Example 2 and Comparative Example 3).

In addition, the diarrhea observed in the Bofutsushosan group (Comparative Example 2) did not occur in the Bofutsushosan / Oshiba Koto group. In this way, by combining Bofutsushosan and Daisaikoto while reducing the ratio, a higher liver fat reduction effect is exhibited compared to the case of full administration of each (Bofutsushosan group, Daisaikoto group), and further. It was confirmed that the side effects seen in Bofutsushosan were reduced.

Claims (4)

A pharmaceutical composition for reducing liver fat containing (A) bofutsushosan extract powder and (B) daisaikoto extract powder. The pharmaceutical composition for reducing liver fat according to claim 1, which contains 0.05 to 10 parts by weight of the component (B) with respect to 1 part by weight of the component (A). The pharmaceutical composition for reducing liver fat according to claim 1 or 2, wherein the daily dose of the component (A) is set to 500 to 10000 mg. The pharmaceutical composition for reducing liver fat according to any one of claims 1 to 3, wherein the daily dose of the component (B) is set to 400 to 8000 mg.