WO2009093353A1 - Composition médicinale - Google Patents

Composition médicinale Download PDF

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Publication number
WO2009093353A1
WO2009093353A1 PCT/JP2008/066851 JP2008066851W WO2009093353A1 WO 2009093353 A1 WO2009093353 A1 WO 2009093353A1 JP 2008066851 W JP2008066851 W JP 2008066851W WO 2009093353 A1 WO2009093353 A1 WO 2009093353A1
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Prior art keywords
pantethine
sennoside
group
effect
weight
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PCT/JP2008/066851
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English (en)
Japanese (ja)
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Naoko Harada
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Kobayashi Pharmaceutical Co., Ltd.
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/10—Laxatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to a pharmaceutical composition having few side effects caused by Fukatsu-san, especially a pharmaceutical composition having an effect of improving constipation, anti-obesity and liver function.
  • Fengtsu Sansho a Chinese herbal medicine
  • Such an effect is thought to be due to sennoside, a component of Daio contained in Fukatsu-Don Seisaku.
  • Sennoside is a kind of anthraquinone compound and is absorbed from the small intestine and is said to promote defecation by stimulating the mucous membrane of the large intestine in a hematogenous manner.
  • Patent Document 1 Non-Patent Document 1
  • Fengtsu Sansho is effective for anti-obesity, particularly the reduction of internal fat (see, for example, Non-Patent Documents 2 and 3). Care should be taken when using Fengtsu Sansho for obese people who are included and tend to have impaired liver function.
  • Panthetin is known to promote peristaltic movement of the intestinal tract (Non-Patent Document 4), and acts on the parasympathetic nervous system to promote peristaltic movement of the intestine. was there.
  • pantethine is known to have an effect of promoting lipid metabolism such as a cholesterol reduction effect and a neutral fat reduction effect (see, for example, Non-Patent Documents 5 and 6), but the effect is slow and sufficient. It wasn't.
  • Non-Patent Document 7 Although pantethine is known to be effective in reducing visceral fat (see Non-Patent Document 7), it has not been known to reduce even subcutaneous fat.
  • pantethine has a peristaltic effect promoting effect and a lipid metabolism promoting effect, but a sufficient effect could not be obtained.
  • JP-A-8-310960 Plzenide (registered trademark) lock manufactured by Novartis Pharma KK) package insert Fiscal 2002 Science and Technology Research Fund Regional Leading Research Research Results Report Abstracts of Annual Meeting of the Pharmaceutical Society of Japan (issued March 5, 2003) Medical treatment and new drugs (medical publishing company) 13 (2) 247 (1976) Geriatrics 18 (9) 1275 (1980) Geriatrics 18 (7) 967 (1980) Journal of Atherosclerosis and Thrombosis, 2000 vol.7 55-58
  • the main object of the present invention is to provide a pharmaceutical composition containing Fufutsu Seisaku, which has few side effects and is excellent in constipation improving effect, anti-obesity effect and the like.
  • Another object of the present invention is to provide a method for reducing the side effects caused by taking Fufutsu Seisaku.
  • the present inventor has intensively studied to solve the above problems, and by using a combination of Fengtsu Sansho and Panthetins, an excellent defecation promoting effect, that is, a constipation improving effect can be obtained. It has been found that abdominal pain that tends to occur due to enhanced defecation promoting action is reduced.
  • the present inventor exhibits excellent anti-obesity effect, weight gain inhibitory effect, free fatty acid and serum triglyceride increase inhibitory effect, liver function improving effect, etc. by combining Fufutsu Seisan and panthetins I found out.
  • the present inventor has found that the amount of ketone bodies in the serum, which may lead to acidemia (ketoacidosis), increases due to the taking of Fengtsu Seikisan, and It was found that it can be effectively suppressed by combining with.
  • the present invention has been completed as a result of further research based on such knowledge.
  • the present invention provides the following pharmaceutical composition and a method for reducing the side effects of Fukatsu Sansho.
  • Item 1. (A) component: (B) Component: A pharmaceutical composition comprising at least one pantethine selected from pantethine, pantethine salt, pantothenic acid, pantothenic acid salt, pantethein and panthenol.
  • Item 2. Item 2. The pharmaceutical composition according to Item 1, wherein the blending ratio of component (B) to 2 parts by weight of 1 part by weight of sennoside in component (A) is 2 to 800 parts by weight.
  • Item 3. Item 3.
  • the pharmaceutical composition according to Item 1 or 2 which is used for improving constipation.
  • Item 4. Item 3.
  • Item 3. The pharmaceutical composition according to Item 1 or 2, which is for improving liver function.
  • Item 7. Item 7. The method according to Item 6, wherein the side effect of Feng Shui-san is abdominal pain and / or an increase in serum ketone bodies.
  • the pharmaceutical composition of the present invention can exhibit an excellent defecation promoting action (ie, constipation improving action) and the like, although there are few side effects.
  • Ingredient (A) of the present invention Fengtsu Sansho is abdominal pain when used in a large amount to promote defecation, and its effect diminishes when used continuously. As a result, habitual use is necessary. The vicious circle of becoming was a problem.
  • the pharmaceutical composition of the present invention an excellent defecation promoting effect can be realized by combining the component (B): panthetins, and there is no abdominal pain. It is suitable for.
  • panthetins act on the parasympathetic nerves to promote natural defecation, and therefore, according to the pharmaceutical composition of the present invention, there is low concern about addictive properties and excellent safety.
  • the pharmaceutical composition of the present invention significantly suppresses an increase in body weight due to excessive intake of lipids.
  • the pharmaceutical composition of the present invention is also useful as an anti-obesity pharmaceutical composition because of its excellent inhibitory effect on the increase in free fatty acids and serum triglycerides.
  • the present invention is an extremely excellent pharmaceutical composition that can effectively improve the side effects and problems caused by taking Fengtsu Sansho in addition to the effects of improving bowel movement and anti-obesity. is there.
  • it is excellent in reducing the side effects such as abdominal pain and increased serum ketone body caused by taking Fukatsutsu Seisaku. That is, it is not limited to uses such as improvement of constipation, but has an excellent effect of reducing side effects in all pharmaceutical compositions containing Fufutsu Seisaku.
  • the present invention also provides a method for reducing the side effects of Fengtsu Sansho by using Fudotsu Seiki and panthetin together.
  • the pharmaceutical composition of the present invention is mainly characterized in that it contains (A) component: Fufutsu Seisaku and (B) component: panthetins.
  • a component Fufutsu Seisaku
  • B component: panthetins.
  • Windproof Tsushosan The component (A) of the present invention is Windproof Tsushosan.
  • Wind-proof sangsan used in the pharmaceutical composition of the present invention includes: Toki, Peonies, Senkyu, Sanshi, Forsythia, Hakka, Pepper, Keigai, Bowfu, Maou, Daio, Bowshaw, Sandalwood, Kyokyo, Ogon, Ganzo, Gypsum And an extract of a mixture of Kasseki.
  • Fufutsu Seisaku which is the component (A) of the present invention, is defined in the ⁇ Basic Handling Policy of Kampo Preparations '' established by the Kampo Herbal Medicine Research Committee.
  • the Kampo prescriptions (herbal medicine blends) described in the letter and extracts obtained from these Kampo prescriptions are included.
  • an extract preparation of Fengtsu Seisaku can be used.
  • the extract obtained by the above-mentioned method is concentrated under reduced pressure to obtain a dry extract by a spray drying method, or an adsorbent suitable for a soft extract with an increased concentration of the extract (for example, anhydrous For example, silicic acid, starch, etc.).
  • Toki 1.2 parts by weight, the same applies hereinafter
  • the method for producing the extract of Fuyutsu Seisaku also adds 400 parts by weight of water to each of the above components other than bowsho, decocts up to 200 parts by weight, removes residue, and then adds bowsho (for example, “Wakan” Some of them are slightly different from the above, such as “Yaku Handbook”, Michinori Kubo, Kenzo Moriyama, published by Yoikusha.
  • these differences are not particularly limited, and any of these differences are included as a windproof sansho.
  • Examples of the extract preparations of Fukatsutsu Seisaku are, for example, Fudotsu Seisaku Dry Extract A, Fadotsu Seisaku Dry Extract AM, Fadotsu Seisaku Dry Extract E, and Fudotsu Seisaku Dry Extract EM (all of which are Nippon Powder Co., Ltd.) ), And Fudotsu-san-san dried extract-C and Fado-san-san-san dried extract-F (both manufactured by Alps Yakuhin Kogyo Co., Ltd.) are known as products and can also be obtained commercially. .
  • Dio used for the preparation of Fengtsu Syosan contains sennoside that causes abdominal pain.
  • sennoside As sennoside, sennoside A which is easily hydrolyzed and sennoside B which is hardly hydrolyzed (both are glycosides and activated by bacteria in the large intestine) are known.
  • the blending ratio 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.
  • the component (A) is usually 0. It is about 0001 to 20% by weight, preferably about 0.001 to 20% by weight, more preferably about 0.001 to 15% by weight.
  • the blending ratio of the component (A) can be appropriately set with reference to the blending ratio converted to the sennoside.
  • it is usually about 0.01 to 95% by weight, preferably about 1 to 90% by weight, more preferably about 5 to 90% by weight, further preferably about 10 to 90% by weight, particularly preferably 30 to 80% by weight. %, Particularly preferably about 50 to 65% by weight.
  • the content of sennoside in the pharmaceutical composition of the present invention can be measured according to a quantitative method known to those skilled in the art.
  • the component (B) of the pharmaceutical composition of the present invention includes at least one pantethine selected from the group consisting of pantethine, pantethine salt, pantothenic acid, pantothenic acid salt, pantethein and panthenol Can be used singly or in combination of two or more, preferably pantethine.
  • Panthethine is represented as bis (2- ⁇ 3-[(2R) -2,4-dihydroxy-3,3-dimethylbutanoylamino] propanoylamino ⁇ ethyl) disulfide, and pantothenic acid (vitamin B5) Also called derivatives or active vitamin B5.
  • pharmaceutically acceptable pantethine or pantothenic acid salt can be used as component (B), for example, alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt and magnesium salt; Examples thereof include mineral acid salts such as hydrochloride, nitrate and sulfate; and organic acid salts such as acetate, citrate and benzoate.
  • alkali metal salts such as sodium salt and potassium salt
  • alkaline earth metal salts such as calcium salt and magnesium salt
  • mineral acid salts such as hydrochloride, nitrate and sulfate
  • organic acid salts such as acetate, citrate and benzoate.
  • the component (B) is a known compound and can be synthesized according to a conventionally known method.
  • products such as pantethine A (Daiichi Sankyo Propharma Co., Ltd.) are also known, It can also be obtained commercially.
  • the compounds used as the component (B) other than pantethine are also known and can be obtained according to conventional methods.
  • the blending ratio of the component (B) is not particularly limited as long as the effects of the present invention are exhibited, but is usually about 0.0001 to 95% by weight, preferably 0.001 to 80% in terms of pantethine. About 0.1% by weight, more preferably about 0.01 to 60% by weight, still more preferably about 0.1 to 45% by weight, and particularly preferably about 0.1 to 15% by weight.
  • the content of pantethine in the pharmaceutical composition of the present invention can be measured according to the quantitative method described in the Japanese Pharmacopoeia Pharmaceuticals Articles / Chemical Drug “Panthetine”.
  • the blending ratio of the component (A) and 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 achieved.
  • the cause Component (B) component in terms of pantethine amount
  • the blending ratio of the component (A) and the component (B) can be appropriately set with reference to the blending ratio converted to the sennoside, for example, the component (A) (Total amount of dry extract) Component (B) (in terms of pantethine amount) is about 0.1 to 30 parts by weight, preferably 0.1 to 25 parts by weight, more preferably 0.2 to 25 parts per 100 parts by weight. About parts by weight. According to this blending ratio, even when Fengtsu Sansho is used, promotion of defecation and reduction of side effects can be effectively obtained, and the pharmaceutical composition is particularly excellent in anti-obesity effect and liver function improving action. be able to.
  • composition of the present invention is a liquid preparation (suspension agent) such as a liquid (including syrup) according to a conventionally known method together with pharmaceutically acceptable excipients, carriers and the like.
  • oral preparations in the form of solid preparations such as tablets, pills, powders, granules, and capsules (including soft capsules).
  • the composition of the present invention is preferably in the form of tablets or capsules such as film-coated tablets, sugar-coated tablets, sweetener-coated tablets, and sublingual tablets.
  • composition of the present invention when the composition of the present invention is a liquid preparation, it can be stored frozen, or it may be stored after removing moisture by lyophilization or the like. Freeze-dried preparations, dry syrups and the like are used by adding sterilized water and dissolving them again at the time of use.
  • a carrier conventionally known in this field can be widely used.
  • carriers include excipients such as lactose, sucrose, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, silicic acid; water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin Binders such as solution, carboxymethylcellulose, shellac, methylcellulose, potassium phosphate, polyvinylpyrrolidone, crystalline cellulose, hydroxypropylcellulose, hypromellose, sodium alginate; dry starch, agar powder, laminaran powder, sodium bicarbonate, polyoxyethylene sorbitan fatty acid Disintegrants such as esters, sodium lauryl sulfate, monoglyceride stearate, starch, crospovidone, povidone, low-substituted hydroxypropylcellulose; stearin,
  • the tablets can be made into tablets with ordinary coatings as necessary, for example, sugar-coated tablets, gelatin-encapsulated tablets, enteric-coated tablets, film-coated tablets, double tablets, and multilayer tablets.
  • the composition containing the said active ingredient can be filled into the conventionally well-known capsule which uses gelatin, a pullulan, starch, gum arabic, hydroxypropyl methylcellulose (HPMC), etc. as a raw material, and can be set as a capsule.
  • a conventionally well-known thing can be widely used as a support
  • excipients such as glucose, lactose, starch, cacao butter, hydrogenated vegetable oil, kaolin and talc, binders such as gum arabic powder, tragacanth powder, gelatin and ethanol, and disintegrants such as laminaran and agar. Can be used.
  • surfactants for example, surfactants, absorption promoters, adsorbents, fillers, preservatives, stabilizers, emulsifiers, solubilizers, salts that regulate osmotic pressure, dosage units of the preparations obtained It can be appropriately selected and used according to the form.
  • active ingredients such as amino acids, vitamins, and organic acid salts may be included.
  • active ingredients include valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, asparagine, glutamine, serine, cysteine, cystine, tyrosine, proline, hydroxyproline, aspartic acid, glutamic acid
  • Amino acids such as hydroxy lysine, arginine, ornithine and histidine
  • vitamins such as vitamin A1, vitamin A2, carotene, lycopene (provitamin A), vitamin B6, vitamin B1, vitamin B2, ascorbic acid, nicotinamide and biotin
  • alkali metal salts such as sodium chloride and potassium chloride
  • organic acid salts such as citrate, acetate and phosphate.
  • the pharmaceutical composition of the present invention can be prepared in the form of powder, fine granules, granules, tablets, capsules and the like. These forms can be prepared by using ordinary methods in the art. For example, tablets can be appropriately added with components (A), (B) and other excipients necessary for obtaining tablets, It can be obtained by tableting after mixing and dispersing well. In addition, the powder can be obtained by appropriately adding the components (A), (B) and other excipients necessary for obtaining the powder, and pulverizing them by a suitable method.
  • the daily intake when the pharmaceutical composition of the present invention is prepared into various preparations can be appropriately changed according to the patient's condition and the degree of symptoms, but the daily dose for one adult (body weight 60 kg) is (
  • the amount of sennoside of component A) is usually about 0.01 to 50 mg, preferably about 0.1 to 40 mg, more preferably about 0.1 to 30 mg, still more preferably about 0.1 to 15 mg, particularly preferably 0.1. About 10 mg, most preferably about 0.1 to 8 mg.
  • the dose of sennoside having side effects such as strong abdominal pain can be reduced, and nevertheless, sufficient defecation promoting effect, constipation improving effect, and anti-obesity effect are exhibited. Can do.
  • the dry extract is usually about 0.1 to 10 g, preferably about 1 to 8 g, more preferably about 1.5 to 6 g.
  • the pharmaceutical composition of the present invention is usually used in the form of oral administration by dividing 1 to 3 times a day.
  • the dose time is not particularly limited, but is preferably before meals, between meals or before going to bed.
  • side effects such as strong abdominal pain and an increase in the amount of ketone bodies in serum can be suppressed, and sufficient defecation promoting effect, constipation improving effect, and anti-obesity effect can be exhibited. .
  • the pharmaceutical composition of the present invention can be used for promoting defecation, and is particularly useful for the prevention, symptom improvement and treatment of constipation.
  • constipation as defined by the Japan Society of Internal Medicine, means “a state in which there is no bowel movement for 3 days or more, or even if there is a bowel movement every day, the feeling of residual stool does not go away.” In many cases, the number of flights decreases In addition to hard stools, residual stool feeling, abdominal pain, abdominal distension, vomiting, and anorexia are accompanied.
  • the pharmaceutical composition of the present invention is also useful as an anti-obesity pharmaceutical composition because it is excellent in the effect of increasing body weight due to excessive intake of lipids and the effect of suppressing the increase in free fatty acids and serum triglycerides.
  • the pharmaceutical composition of the present invention has an effect of improving liver function. Since Ougong, which may cause liver dysfunction, is included in Fengtsu Sanseiki, it is not desirable to take Fengtsu Sanse to obese people whose liver function tends to decrease. However, the pharmaceutical composition of the present invention can be used with peace of mind even for such obese people.
  • Fengshutsu Seisaku has side effects such as abdominal pain and increased ketone body in serum when taken alone, but the pharmaceutical composition of the present invention reduces these side effects and Or it can be prevented. Therefore, the present invention also provides a pharmaceutical composition for reducing and / or preventing side effects of Fukatsutsu Seisaku.
  • Each component used in the method for reducing side effects of Fukatsutsu Seisaku, its blending amount, and the like are as described above.
  • Test Example 1 Effect of improving constipation in rats [subjects] SD rats (4 weeks old) males were acclimated for 1 week with the normal diet “CE-2” (manufactured by CLEA Japan, Inc.) (average weight at acclimation: 180 g).
  • the acclimated rats were divided into 5 groups ((i) normal group, (ii) control group, (iii) Fengtsu Sansho group, (iv) pantethine group, (v) windbreak) according to the test drug administration components listed in Table 2.
  • Tsushosan / pantethine group (9 / group), and each group was reared for 85 days with a normal feed or a high fat / low dietary fiber feed of the mixing ratio shown in Table 1 (during the breeding period, rats Were given free access to food and water).
  • Each group was orally administered once a day with test substances (pantethine, sennoside, Fufutsu Seisaku) shown in Table 2. Distilled water was administered to the control group.
  • Normal feed is “CE-2” (manufactured by Clea Japan Co., Ltd.)
  • pantethine is 80% by weight panthetin aqueous solution “Pantetine A” (manufactured by Daiichi Fine Chemical Co., Ltd.)
  • lard and corn starch are those manufactured by Clea Japan Co., Ltd. Each was used.
  • the amount of pantethine in the table is a value calculated from the pantethine content of pantethine A (80% by weight).
  • the wind-proof tsusan-san is converted to dry weight as Toki 1.2 (parts by weight, the same applies hereinafter), Peonies 1.2, Senkyu 1.2, Sanshi 1.2, Forsythia 1.2, and mint. 1.2, Show 1.2, Kei-Gai 1.2, Bow Fu 1.2, Maou 1.2, Daio 1.5, Bow Show 1.5, Sandalwood 2.0, Kyo 2.0, Ogon 2.0, Licorice 2.0, Gypsum 2.0 and Kasseki 3.0 were extracted with 20 times the weight of water (560 parts by weight) at about 100 ° C. for 1 hour, centrifuged to obtain an extract, and concentrated under reduced pressure. Then, using “drying tsushosan extract” (spray dryer drying was performed by dropping the extract into an atomizer with a rotational speed of 10000 rpm and supplying hot air at 150 ° C.) It was.
  • sennoside was pulverized in a mortar using “Pruzenide (registered trademark) tablets” (12 mg as sennoside) manufactured by Novartis Pharma, and orally administered according to Table 2.
  • the improvement was evaluated as a ratio to the amount of defecation in the control group, the sennoside group, the sennoside / pantethine group, and the Fufutsu Seiki group showed a decrease in the degree of improvement in constipation after long-term use for 42 days.
  • the Fengtsu Sansho / Pantethine group there was a tendency to maintain and improve the effect of improving constipation during the test period.
  • constipation drugs In the use of constipation drugs, it is known that resistance and habituation to the drugs occur in the long-term use, and the effect of the drugs becomes difficult to be exerted, and as a result, the effect of improving constipation is attenuated. However, from these results, it was shown that such a decrease in constipation-improving effect was not observed by using Fufutsu Seisan and Panthetin together.
  • Test Example 2 Improvement of constipation in humans (I) Five groups ((i) take pantethine in advance) so that the number of defecations, defecation amount, etc. are evenly distributed among 50 men (average age: 31.8 years old) who are not constipated in a questionnaire about defecation status Panthetin group, (ii) Fengtsu Seikisan group taking Fengtsu Seikisan, (iii) Fufutsu Seikisan and Pantethine group taking Panthetin, (iv) Sennoside group taking sennoside, ( v) Sennoside and pantethine group taking sennoside and pantethine).
  • the windproof sansho and sennoside used in this test example are the same as those in the test example 1.
  • As pantethine Daiichi Sankyo's “Pantosine Tablet 100” (100 mg as pantethine) was used, and the dose per administration was 1 tablet.
  • Table 4 summarizes the test drugs and doses administered to each test group. The results are shown in Tables 5 and 6 below.
  • Test Example 3 Improvement of constipation in humans (II) Preliminary questionnaire on defecation status for 30 men with constipation (average age: 32.3 years) Panthetin group, (ii) Fengtsu Seikisan group taking Fengtsu Seikisan, (iii) Fengtsu Seikisan and Panthetin group taking Panthetin, (iv) Sennoside group taking sennoside, v) Sennoside and pantethine group taking sennoside and pantethine).
  • the present invention it was possible to improve the defecation promoting effect without increasing the dose of Fufutsu Seisaku. Moreover, the effect which reduces the side effect (abdominal pain) of a wind-proof Tsushosan to pantethin was confirmed. That is, according to the pharmaceutical composition of the present invention, it was shown that the desired defecation can be realized and the side effects (abdominal pain) of Fengtsu Sansho can be reduced.
  • the number of defecations was improved in the pantethine group only for constipated persons, but in the sennoside group, the sennoside pantethine group, the Fufutsu Seisan group and the Fufutsu Seisan / Pantethine group Improved in both constipated and non-constipated people.
  • the Fufutsu Seisan / Pantetin group improved 3.33 times before and after taking constipation, and 1.89 times that of non-constipation, and was particularly effective against constipation. Demonstrated.
  • Test Example 4 Abdominal pain suppression effect in humans Preliminary questionnaire on defecation status for 50 men (average age: 31.4 years) who are not constipated in 5 groups ((i) magnesium oxide group taking magnesium oxide, (ii) pantethine Pantethine group to be taken, (iii) Fudotsu Seiki group to take Fudotsu Seiki, (iv) Fudotsu Seiki and Magnesium oxide group to take Fudotsu Seiki and magnesium oxide, (v) Fudotsu Seiki And sennoside and pantethine group taking pantethine).
  • the dose per time in each group is shown in Table 9 below.
  • Each group was given the test drugs shown in Table 7 for 5 days, 3 times a day, between meals or before meals, and answered whether there was abdominal pain.
  • Test Example 5 After the end of Liver Function Elevating Effect Test Example 1 in rats, a 85-day long-term administration test was conducted under the same test conditions. On day 85, blood was collected and dissected, and the AST value in serum was measured and the liver was visually observed by autopsy. The results are shown in Tables 11 and 12 below.
  • the serum AST value can be used as an evaluation factor for liver function because the value in the blood increases abnormally as hepatocyte destruction (disorder) progresses. The smaller the value, the lower the risk of liver damage. Further, in the naked eye observation, it is possible to estimate the progression of fatty liver and liver damage by fading of the liver.
  • the control group showed an increase in the AST value compared to the normal group when fed the diet of high fat and low dietary fiber.
  • the pantethine group there was no change in the AST value, and in the Fufutsu Seisaku group, a slight decreasing tendency was seen.
  • the value was significantly decreased in the Fengtsu Sansei / Pantetine group.
  • this value is compared with the control group being 1, a significant decrease in the AST value is seen in the Fengtsu-san-san / pantethine group, and it is considered that hepatic function is improved by the combined use of Fado-san-san and panthetin.
  • the acclimated rats were divided into 5 groups ((i) normal group, (ii) control group, (iii) Fengtsu Seiki group, (iv) Pantethine group, (v) Fukatsu sansho) according to the diet shown in Table 13.
  • -Panthetin group (8 animals / group), and each group was reared for 40 days on a high-fat diet with the mixing ratio shown in Table 13 (during the breeding period, rats were allowed to freely feed and feed) )
  • Blood was collected on the 32nd day from the start of breeding, and the amounts of neutral fat, free fatty acid and ketone bodies in the serum were measured according to the enzyme method.
  • visceral fat percentage and body fat percentage were measured using a CT apparatus LaTheta LCT-100 (manufactured by Aroka Co., Ltd.) on the 40th day from the start of breeding with a high fat diet.
  • Normal feed is “CE-2” (manufactured by Clea Japan Co., Ltd.)
  • pantethine is 80% by weight panthetin aqueous solution “Pantetine A” (manufactured by Daiichi Fine Chemical Co., Ltd.)
  • lard and corn starch are those manufactured by Clea Japan Co., Ltd. Each was used.
  • the amount of pantethine in the table is a value calculated from the pantethine content of pantethine A (80% by weight).
  • ketone bodies made from lipids in the body are not used as energy well, and if the amount of ketone bodies continues to increase, acidemia (ketoacidosis) can occur. Therefore, the suppression of the increase in the amount of ketone body is very preferable as efficient lipid metabolism and prevention of acidemia.
  • tablets were produced by a conventional method.
  • 10 is a graph showing the weight change of rats in Test Example 6. It is a graph showing the result of the measured value of the neutral fat in rat serum, a free fatty acid, and a ketone body in the test example 6.

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Abstract

[PROBLÈME] Obtenir une composition médicinale très efficace pour combattre la constipation et l'obésité et améliorer les fonctions du foie. [SOLUTION] Une composition médicinale comprenant du Bofutsushosan et au moins un composé de pantéthine sélectionné parmi la pantéthine, des sels de pantéthine, l'acide pantothénique; des sels de l'acide pantothénique, la pantéthéïne, et le panthénol.
PCT/JP2008/066851 2008-01-25 2008-09-18 Composition médicinale WO2009093353A1 (fr)

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Publication number Priority date Publication date Assignee Title
JP2015189748A (ja) * 2014-03-28 2015-11-02 小林製薬株式会社 医薬組成物
JP2018131451A (ja) * 2018-04-25 2018-08-23 小林製薬株式会社 医薬組成物

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JP7133982B2 (ja) * 2017-08-10 2022-09-09 小林製薬株式会社 錠剤組成物

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Publication number Priority date Publication date Assignee Title
JP2000191524A (ja) * 1998-12-25 2000-07-11 Pasuteru:Kk 便秘改善組成物
JP2007112795A (ja) * 2005-09-26 2007-05-10 Takeda Chem Ind Ltd アントラキノン系薬剤含有下剤医薬組成物
JP2007297331A (ja) * 2006-04-28 2007-11-15 Rohto Pharmaceut Co Ltd パントテン酸類含有水性組成物

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Publication number Priority date Publication date Assignee Title
JP2000191524A (ja) * 1998-12-25 2000-07-11 Pasuteru:Kk 便秘改善組成物
JP2007112795A (ja) * 2005-09-26 2007-05-10 Takeda Chem Ind Ltd アントラキノン系薬剤含有下剤医薬組成物
JP2007297331A (ja) * 2006-04-28 2007-11-15 Rohto Pharmaceut Co Ltd パントテン酸類含有水性組成物

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2015189748A (ja) * 2014-03-28 2015-11-02 小林製薬株式会社 医薬組成物
JP2018131451A (ja) * 2018-04-25 2018-08-23 小林製薬株式会社 医薬組成物

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