WO2009093736A1 - Tablet comprising kanpo herbal medicine and pantethine component - Google Patents

Tablet comprising kanpo herbal medicine and pantethine component Download PDF

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Publication number
WO2009093736A1
WO2009093736A1 PCT/JP2009/051228 JP2009051228W WO2009093736A1 WO 2009093736 A1 WO2009093736 A1 WO 2009093736A1 JP 2009051228 W JP2009051228 W JP 2009051228W WO 2009093736 A1 WO2009093736 A1 WO 2009093736A1
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Prior art keywords
tablet
pantethine
hardness
salt
weight
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PCT/JP2009/051228
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French (fr)
Japanese (ja)
Inventor
Naoko Harada
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Kobayashi Pharmaceutical Co., Ltd.
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Publication of WO2009093736A1 publication Critical patent/WO2009093736A1/en

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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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics

Definitions

  • the present invention relates to a tablet containing a Chinese medicine having desired mechanical strength and disintegration.
  • tablets are used in many pharmaceuticals, health foods, and the like because they are easy to take as one unit of measurement, are easy to take, and are relatively easy to manufacture. Tablets are packaged and then transported after being tableted. In this process, the tablet is subjected to considerable external forces such as vibration and impact. It must be tableted to have strength (hardness).
  • Non-patent Document 1 As one means for increasing the hardness of tablets, it is known to increase tableting pressure (Non-patent Document 1).
  • tableting pressure is undesirable because it causes capping (peeling of the upper surface of the tablet), lamination (lamellar peeling), and the like during tableting.
  • capping peeling of the upper surface of the tablet
  • lamination lamination
  • the like during tableting.
  • disintegration is lowered by increasing the hardness.
  • Non-Patent Documents 2 and 3 As means for improving the disintegration of tablets, (1) Addition of disintegrants such as starch and cellulose, (2) Use of foaming action by acid-base reaction (addition of foaming agent), (3) Trace amount of lubricant (External lubrication) is known (Non-Patent Documents 2 and 3). However, since the blending amount of raw materials per tablet is limited to some extent, “adding disintegrants and foaming agents” reduces the blending amount of active ingredients and the like. The problem is that the effect obtained by “miniaturization of the agent” is small.
  • an object of the present invention is to provide a tablet containing a Chinese medicine having an excellent effect in terms of mechanical strength and disintegration.
  • the present inventor mixed all or part of herbal medicine and other ingredients constituting the tablet, granulated the mixture into granules, and then tableted by a conventional method to produce tablets.
  • the inventor mixed all the materials constituting the tablet, and then directly tableted the obtained mixture by a conventional method to produce a tablet.
  • the tablet that was tableted through the former granulation process has higher hardness than the latter tablet that was directly tableted without going through the granulation process, and therefore the tablet strength can be changed by changing the manufacturing method. Improvement was observed. However, even in the case of the tablet, it is still insufficient as a tablet that can endure distribution as a commercial product.
  • starches such as corn starch, which are known excipients for traditional Chinese medicine, sugars such as lactose and sucrose, binders such as starch paste and hydroxypropylcellulose, and the like. I tried a lot of manufacturing. However, even in this case, the hardness and disintegration were not satisfactory.
  • the present inventor has conducted extensive research in view of the above-mentioned problems, and the hardness is improved by containing Fufutsu Seisaku, Daisaikoku Daihoyu, Hosai Kotoyu or Daishibayu and panthetin, and It has been found that tablets with a reduced disintegration time can be obtained. That is, it is considered that pantethines have the effect of improving the hardness of tablets containing Chinese medicine and shortening the disintegration time.
  • the present invention has been completed as a result of further studies based on the above findings, and is described below.
  • Tablet (1-1) At least one herbal medicine selected from the group consisting of Fufutsu Seisaku, Daishiba-ku Daiho-to, Hosai-ko-to and Dai-saiko-to, and pantethine, pantethine salt, pantothene
  • the tablet according to (1-1) wherein the tablet has a vertical hardness of 6N or more.
  • Hardness improvement method disintegration improvement method (3-1) at least one Chinese herbal medicine selected from the group consisting of Fukatsutsu Seisaku, Daishiba-ku-Dai-Yo-to, Ho-Kai-Dao-yu and Dai-saiko-to, A method for improving the hardness of a tablet containing the above-mentioned Chinese medicine, which is used in combination with at least one type of pantethine selected from pantethine, a salt of pantethine, pantothenic acid, a salt of pantothenic acid, pantethein and panthenol.
  • At least one herbal medicine selected from the group consisting of Fufutsu Seisaku, Daisaikoku Daioyu, Hosaihoyuto, and Daisaikoto, and pantethine, pantethine salt, pantothenic acid, pantothenic acid
  • pantethine, pantethine salt pantothenic acid
  • pantothenic acid pantothenic acid
  • At least one herbal medicine selected from the group consisting of Fufutsu Seisaku, Daisaikoku Daihoyu, Hosaihoyuto, and Daisaikoto, and pantethine, pantethine salt, pantothenic acid, pantothenic acid
  • pantethine selected from the salts of:
  • the tablet of the present invention has a mechanical strength that can sufficiently withstand external forces such as vibration and impact received from tableting to taking. Moreover, the tablet of this invention has moderate disintegration which disintegrates in a fixed time after taking.
  • the effects specific to the traditional Chinese medicine the effect on cholesterol derived from panthetin and the effect of activating peristaltic movement of the intestine can be obtained simultaneously. Can do.
  • the mechanical strength can be increased and the disintegration time can be shortened in tablets containing Chinese medicine.
  • the mechanical strength can be increased, the disintegration time can be shortened, and a tablet having a desired effect can be obtained. Can do.
  • the tablet of the present invention is mainly characterized by containing a specific Chinese medicine and panthetins.
  • the configuration of the present invention will be described in detail.
  • Traditional Chinese Medicine Examples of the traditional Chinese medicines to be blended in the tablet of the present invention include Fufutsu Seisaku, Daisai Kodoku Daiho-to, Hosei Korei-to and Dai-saiko-to.
  • As herbal medicines Fufutsu Seisaku and Daisaikoto are preferred because they are excellent in hardness and disintegration.
  • the Chinese medicine is in the form of extract or extract powder.
  • the Chinese medicine is preferably in the form of an extract powder.
  • Chinese medicines may be blended alone or in combination.
  • Kyo (Zingiber officinale Roscoe), Kaigai (Schizonepeta tenuifolia Briquet), Forsythia suspense Vahl, Forsythia viridissimilarisindimilidisimidalysidimaisiridaisimidalysidimaisiridaisimidalysidimaisiridaisimidalysidimaisiramidilesimilaridsimilamisiramidilesidis tiloba Kitagawa, Angelica acutiloba Kitagawa var.
  • piperascens Malinvaud ), storm (Saposhnikovia divaricata Schischkin) , Rheum palmatum Linne, Rheum tanguticum Maximowicz, Rheum officin ble Baillon, Rheumcoreanum Nakai or their interspecific hybrids), Byakujutsu (Atractylodes japonica Koidzumi ex Kitamura, Atractylodes ovata De Candolle), bellflower (Platycodon grandiflorum A.
  • the above Chinese herbal medicine is obtained from the raw materials shown in Table 1 below.
  • plant raw materials have specified use sites according to the Japanese Pharmacopoeia.
  • the above-mentioned Kampo medicine used in the present invention is described in the Chinese medicine-related letters currently in use as defined in the “Basic Handling Policy of Kampo Preparations” established by the Kampo Herbal Medicine Research Committee.
  • Herbal prescriptions (herbal medicine blends) and extracts obtained from these Chinese herbal prescriptions are included.
  • the Chinese herbal medicine may use the obtained extract (extract form) or a so-called extract powder (extract powder form) obtained by formulating the extract by a conventional method.
  • extract powder for example, about 10 to 20 times the amount of water is added to the mixture of the above components, and the mixture is stirred and extracted at about 80 to 100 ° C. for about 1 to 3 hours. , Filtered to obtain an extract, which is concentrated under reduced pressure and made into a dry extract powder by a spray drying method, or an adsorbent suitable for a soft extract with an increased concentration of the extract (eg, silicic anhydride, starch, etc.) ) To obtain an adsorbent extract powder.
  • adsorbent suitable for a soft extract with an increased concentration of the extract
  • Fukatsutsu Seisan is converted to dry weight of raw materials, such as Toki 1.2 (parts by weight, hereinafter the same), Peonies 1.2, Senkyu 1.2, Sanshi 1.2, Forsythia 1. 2, mint 1.2, show 1.2, kei guy 1.2, bow 1.2, maow 1.2, dio 1.5, bow show 1.5, peacock 2.0, kyo 2.0, oggon 2 0.0, Licorice 2.0, Gypsum 2-3 and Kasseki 3-5 are extracted with 20 times their weight (and hence 560-620 parts by weight) of hot water, then concentrated to 1/2 volume, The extract powder can be used as an extract, and an extract powder is produced from this extract.
  • raw materials such as Toki 1.2 (parts by weight, hereinafter the same)
  • mint 1.2 show 1.2, kei guy 1.2, bow 1.2, maow 1.2, dio 1.5, bow show 1.5, pea
  • these differences are not particularly limited, and any of these differences are included as a windproof sansho.
  • the wind-proof scented powder extract that can be used in the present invention can be produced as described above.
  • Dried extract E and Fufutsu Seisan dried extract EM both manufactured by Nihon Powder Co., Ltd.
  • Fufutsu Seikoku dried extract-C and Fufutsu Seikoku dried extract-F both manufactured by Alps Pharmaceutical Co., Ltd.
  • Such products are known and can be obtained commercially.
  • Dai-saiko-to is Psycho 6.0 (parts by weight, the same applies hereinafter), Hange 3.0-4.0, Showa 4.0-5.0, Ogon 3.0, Peonies 3.0, Taiso 3.0, Pheasant 2.0, Daio 1.0-2.0, and in principle, this is 20 times the weight (thus 500-560 parts by weight). ) And then concentrated to 1/2 volume, and can be used as an extract from which solid content has been removed, and an extract powder is produced from this extract.
  • Daisaikou Daioyu extract powder Hosai Koyuto extract powder and Daisaikoyu extract powder, for example, Extract A and Housui-Kyuto dry extract AZ (both manufactured by Nihon Powder Co., Ltd.), Houho Kyo-yu extract powder and Hou-Kou Kouyu dried extract-F (both manufactured by Alps Pharmaceutical Co., Ltd.), etc.
  • Daisaikou Daisaikoto dry extract
  • Daisaikoto dry extract AM Daisaikoto dry extract SN and Daisaikoto dry extract powder
  • Daisaikoto dry extract F and Daishiba Products such as kuyu dried extract-F (all manufactured by Alps Pharmaceutical Co., Ltd.) are known and can also be obtained commercially.
  • the blending ratio of the Chinese medicine in the tablet of the present invention is not particularly limited as long as the effect of the present invention is exhibited.
  • the total dry weight of the extract or the total amount of the extract powder is usually 0.01 to 98% by weight in the tablet.
  • the blending ratio is usually about 0.1 to 98% by weight, preferably about 1 to 95% by weight in the tablet.
  • the amount is preferably about 3 to 90% by weight, more preferably about 10 to 90% by weight, particularly preferably about 30 to 80% by weight.
  • the blending amount can be appropriately set so that the effect of the present invention can be obtained with reference to the amount of the above-mentioned Fukatsutsu Seisan.
  • Panthetins The tablet of the present invention is characterized by containing the above-mentioned Chinese medicine and panthetins.
  • the pantethine includes at least one selected from the group consisting of pantethine, pantothenic acid, pantethein, panthenol, and a salt of pantethine or pantothenic acid.
  • the salt of pantethine or pantothenic acid is not limited as long as it is pharmaceutically acceptable, for example, alkali metal salts such as sodium salt and potassium salt, alkaline earth metals such as calcium salt and magnesium salt, hydrochloride salt, Examples thereof include mineral acid salts such as nitrate and sulfate, and organic acid salts such as acetate, citrate and benzoic acid.
  • These panthetins have a similar basic skeleton.
  • pantethine is preferable.
  • 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.
  • Pantethine is a known compound and can be synthesized according to a conventionally known method, but as pantethine, for example, a product such as “Panthetine A” (manufactured by Daiichi Sankyo Propharma) is also known and commercially available. You can also Panthetins other than pantethine are also known and can be obtained according to conventional methods, and commercially available products can also be used.
  • the blending ratio of panthetins in the tablet of the present invention is not particularly limited as long as the effects of the present invention are exerted.
  • it is usually about 0.01 to 95% by weight in terms of pantethine, preferably 0 About 1 to 80% by weight, more preferably about 0.1 to 40% by weight.
  • the blending ratio thereof is usually about 0.01 to 95% by weight, preferably about 0.1 to 80% by weight, more preferably 0.1 to 80% by weight in the tablet. About 40% by weight.
  • the mixing ratio of pantethine to Chinese medicine in the tablet of the present invention is not limited as long as the effect of the present invention is exerted, but the mixture of Chinese medicine and panthetin is not excessively sticky, for example
  • the tablet can be preferably produced without adhering the mixture to the pestle or mortar used for tableting, and the effect on panthetin-derived cholesterol and the effect of activating the peristaltic movement of the intestine are not impaired, and the hardness and Since a tablet excellent in disintegration can be produced, for example, the lower limit of the total amount of panthetins relative to 100 parts by weight of the traditional Chinese medicine is preferably 0.01 parts by weight, more preferably 0.1 parts by weight. More preferably 0.125 parts by weight, particularly preferably 0.2 parts by weight. Moreover, the upper limit of the total amount of panthetins is preferably 30 parts by weight, more preferably 28 parts by weight, and even more preferably 25 parts by weight.
  • the total amount of Fukatsutsu Seisaku and / or Daisaikoto is 100.
  • the lower limit of the total amount of pantethine with respect to parts by weight is preferably 0.1 parts by weight, more preferably 1 part by weight, still more preferably 1.25 parts by weight, particularly preferably 2 parts by weight. is there.
  • the upper limit of the total amount of pantethine is preferably 30 parts by weight, more preferably 28 parts by weight, and even more preferably 25 parts by weight.
  • Size of tablet The size of the tablet of the present invention is not particularly limited as long as the effect of the present invention is exhibited, but is appropriately adjusted according to the use object, purpose of use and the like.
  • the size of the tablet of the present invention is exemplified by a size that is easy to take, preferably 18 mm or less, more preferably 15 mm or less, and even more preferably 12 mm or less.
  • the size of the tablet of the present invention is exemplified by a size that can be easily taken, preferably 10 mm or less in diameter, more preferably 9 mm or less, and still more preferably 8 mm or less.
  • Other components that can be contained in tablets for the tablets of the present invention, for example, those conventionally known in the art can be widely used as carriers.
  • Such 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, stearic acid monoglyceride, starch, crospovidone, povidone, low substituted hydroxypropylcellulose; stearin, cocoa butter, Disintegration inhibitors such as additive oils; Absorption accelerators such as quaternary ammonium salts and sodium lauryl sulfate; Moisturi
  • the tablet of the present invention includes, for example, a surfactant, an absorption accelerator, an adsorbent, a filler, a preservative, a stabilizer, an emulsifier, a solubilizer, and a salt that adjusts osmotic pressure. Can be contained. Furthermore, in addition to the above, the tablet of the present invention may contain other active ingredients such as amino acids, vitamins, and organic acid salts.
  • active ingredients include, for example, 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
  • Examples include alkali metal salts such as sodium chloride and potassium chloride, and organic acid salts such as citrate, acetate and phosphate.
  • 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.
  • Manufacturing method of tablet The manufacturing method of the tablet of this invention is not limited as long as the obtained tablet can exhibit a desired effect, It can manufacture according to a conventionally well-known method.
  • specific materials of Chinese herbal medicine and panthetin, their blending ratio, and the like are appropriately set according to the above description. Usually, it may be tableted by mixing Chinese medicine and pantethine, and other excipients if necessary.
  • the compounding material may be directly compressed, and if tableting is performed according to a conventional method, such as granulating part or all of the compounding material before tableting, and then tableting it. Good.
  • Hardness and disintegration of tablet The hardness of the tablet of the present invention is not particularly limited as long as the effect of the present invention is exhibited.
  • the hardness in the vertical direction is preferably 6N or more, and preferably 8N or more. More preferably, it is more preferably 10N or more.
  • the hardness of the tablet is measured using a Kiya type digital hardness meter KHT-20N type (Fujiwara Manufacturing Co., Ltd.).
  • the disintegration property of the tablet of the present invention is not particularly limited as long as the effect of the present invention can be obtained because it can be changed according to the size, shape, pressure at the time of tableting, etc.
  • the reversal of the disintegration time (T X ) of a tablet made of Chinese medicine and pantethine with respect to the disintegration time (T 0 ) of a tablet made of Chinese medicine alone is evaluated by the reciprocal of (T 0 / T X ).
  • the tablet when Fengtsu Sansho and / or Dai-saiko-to is used as a traditional Chinese medicine and a convex tablet having a diameter of 9 mm is compressed at a pressure of 25 Mpa, the tablet is disintegrated.
  • the improvement in property is not particularly limited, but is preferably 5% or more, more preferably 8% or more, and further preferably 10% or more.
  • the disintegration time of the tablet can be measured by the disintegration time measurement method described in the Japanese Pharmacopoeia. However, other test conditions may be set as appropriate, and the disintegration time in the aqueous solution may be measured. For example, a 100 ml beaker It is also possible to add 80 ml of water at 37 ° C., rotate a 2 cm stirrer bar at 400 rpm, and measure the time from when the tablet is inserted until the tablet cannot be visually observed.
  • the daily intake of the tablet of the present invention can be appropriately changed according to the subject of intake.
  • the dose for one adult is usually 0.01% in terms of the total dry weight or the total amount of the extract powder of Chinese herbal medicine extract.
  • About 12 g preferably about 0.05 to 10 g, more preferably about 0.07 to 8 g.
  • the total dry weight or extract powder of the extract is usually about 0.1 to 10 g, preferably about 1.0 to 8 g, more preferably 1.5 to 6 g. Degree.
  • the pharmaceutical composition of the present invention is usually used in the form of oral administration divided into 2 to 3 times a day.
  • the dose time is not particularly limited, but is preferably before or between meals.
  • the tablet hardness improver of the present invention comprises at least one pantethine selected from pantethine, pantethine salt, pantothenic acid, pantothenic acid salt, pantethein and panthenol.
  • pantethine selected from pantethine, pantethine salt, pantothenic acid, pantothenic acid salt, pantethein and panthenol.
  • Chinese herbal medicine selected from the group consisting of Fufutsu Seisaku, Daishiba-ku-Daiko-to, Ho-so-Hao-yu and Dai-saiko-to it can.
  • Specific materials of panthetins and herbal medicines, their blending ratios, and the like are appropriately set according to the above description.
  • the said improvement agent is manufactured by tableting according to the manufacturing method of the said tablet.
  • the tablet disintegration improver of the present invention comprises pantethine, pantethine salt, pantothenic acid, pantothenic acid salt, pantethein and panthenol as an active ingredient.
  • the disintegration time of the tablet containing at least one Chinese herbal medicine selected from the group consisting of Fukatsutsu Seisaku, Daisaikoku Daihoto, Hosaihokanto and Daisaikoto can be shortened. Specific materials of panthetins and herbal medicines, their blending ratios, and the like are appropriately set according to the above description.
  • the said improvement agent is manufactured by tableting according to the manufacturing method of the said tablet.
  • the tablet hardness and disintegration improver of the present invention comprises at least one panthetin selected from pantethine, pantethine salt, pantothenic acid, pantothenic acid salt, pantethein and panthenol as an active ingredient.
  • it can increase the hardness of tablets containing at least one Chinese herbal medicine selected from the group consisting of Fufutsu Seisaku, Daisaikoku Daihoyu, Hosaihoyuto, and Daisaikoto. It can be shortened. Specific materials of panthetins and herbal medicines, their blending ratios, and the like are appropriately set according to the above description.
  • the said improvement agent is manufactured by tableting according to the manufacturing method of the said tablet.
  • Hardness improvement method, disintegration improvement method According to the hardness improvement method of the tablet of the present invention, it is selected from the group consisting of Fufutsu Seisaku, Daisaikoku Daioyu, Hosaikouyuto, and Daisaikoto.
  • Hardness of a tablet containing the above-mentioned Chinese medicine by using at least one kind of Chinese medicine and at least one kind of pantethine selected from pantethine, pantethine salt, pantothenic acid, pantothenic acid salt, pantethein and panthenol Can be increased. Specific materials of panthetins and herbal medicines, their blending ratios, and the like are appropriately set according to the above description.
  • the said improvement agent is manufactured by tableting according to the manufacturing method of the said tablet.
  • the method for improving disintegration of a tablet of the present invention at least one herbal medicine selected from the group consisting of Fufutsu Seisaku, Daisaikoku Daihoto, Hosaihoyuto, and Daisaikoto, pantethine, pantethine
  • the disintegration time of the tablet containing the above Chinese medicine can be shortened.
  • Specific materials of panthetins and herbal medicines, their blending ratios, and the like are appropriately set according to the above description.
  • the said improvement agent is manufactured by tableting according to the manufacturing method of the said tablet.
  • At least one herbal medicine selected from the group consisting of Fufutsu Seisaku, Daisaikoku Daihoto, Hosai Koreito, and Daisaikoto, and pantethine , Panthetin salt, pantothenic acid, pantothenic acid salt, pantethein and at least one panthetin selected from panthenol can be used together to increase the hardness of the above-mentioned Chinese medicine-containing tablets and disintegrate Time can be shortened.
  • Specific materials of panthetins and herbal medicines, their blending ratios, and the like are appropriately set according to the above description.
  • the said improvement agent is manufactured by tableting according to the manufacturing method of the said tablet.
  • the present invention it is possible to impart superior hardness to tablets compared to the case where a substance conventionally used as a binder such as maltitol, mannitol or sorbitol is used in combination with Chinese medicine instead of pantetins. Further, according to the present invention, hardness and / or disintegration time can be shortened even in tablets containing Chinese herbal medicine, and in tablets containing substances other than Chinese herbal medicine.
  • Example 1 Fengtsu Seiseki and pantethine were mixed at the blending ratio shown in Table 2 below.
  • Toki 1.2 As windproof tsusan san, in terms of raw material dry weight, Toki 1.2 (parts by weight, the same shall apply hereinafter), Peonies 1.2, Senkyu 1.2, Sanshi 1.2, Forsythia 1.2, Hakka 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-Ju 2.0, Ogon 2.0, Licorice 2 0.0, gypsum 2.0 and Kasseki 3.0 were extracted with about 20 times the amount of water at about 100 ° C. for 1 hour, centrifuged to obtain an extract, concentrated under reduced pressure, and spray dried.
  • the dried “Fengshutsu Seisaku Extract Powder” (drying with a spray dryer was performed by dropping the extract into an atomizer with a rotational speed of 10000 rpm and supplying hot air at 150 ° C.).
  • “pantethine A” (manufactured by Daiichi Fine Chemical Co., Ltd.), which is an 80 wt% pantethine aqueous solution, was used.
  • the blending ratios in the table are the values calculated from the dry weight for Fengtsutsu Seisaku Extract powder and the pantethine content (80% by weight) of pantethine A for pantethine, respectively.
  • a convex tablet having a diameter of 9 mm was tableted using a hydraulic tableting machine SMP-3 (manufactured by Riken Seiki Co., Ltd.) at a pressure of 25 Mpa to obtain a tablet. At the time of tableting, it was confirmed whether or not the tablets adhered to the punch or mortar.
  • the obtained tablets were measured for hardness in the direction perpendicular to the tablets using a Kiya type digital hardness tester KHT-20N (manufactured by Fujiwara Seisakusho Co., Ltd.).
  • the vertical direction is the direction of pressing and compressing with a scissors during tableting
  • the horizontal direction is the direction perpendicular to the vertical direction.
  • disintegration time was measured about the obtained tablet, and disintegration evaluation was performed compared with the tablet which consists of a wind-proof tsuyosan alone.
  • the results of the average value of each tablet of 10 tablets are shown in Table 2. (Measurement of disintegration time) A 100 ml beaker was charged with 80 ml of water at 37 ° C., a 2 cm stirrer bar was rotated at 400 rpm, and the time from when the tablet was introduced until the tablet could no longer be observed visually was measured.
  • panthetins when the total amount of panthetins was 100 parts by weight relative to 100 parts by weight of Fukatsu Tsushosan, it was confirmed that the tablets adhered to the punches and mortars during tableting.
  • Example 2 In Example 1, pantethine was used as the pantethine, and “pantocin (registered trademark) powder 50%” (Daiichi Sankyo Co., Ltd.) was used as the pantethine. Except for mixing at the blending ratios shown in Table 3 below, tablets were produced in the same manner as in Example 1 above, the hardness and disintegration time were measured, and the presence or absence of adhesion to the wrinkles and dies during tableting was observed. In addition, the compounding ratio of pantethine was calculated based on the pantethine content (50% by weight) in the fine granules. The results of the average value of 10 tablets for each formulation are shown in Table 3.
  • Example 3 In Example 1, tablets were obtained in the same manner as in Example 1 except that Daisaikoto was used in place of the Fufutsu Seisaku extract powder. As a result, although the hardness was inferior to the result of Example 1 using the Fufutsu Seisaku extract powder, the same tendency as in Example 1 was observed for the hardness and the disintegration time. In addition, tablets were obtained in the same manner as in Example 1 except that Daishiba Kodai Daio-to or Ho-Kai-San-to was used. As a result, the same tendency as in Example 1 was observed with respect to the hardness and the disintegration time, but the hardness was higher in Example 1 using Fufutsu Seisaku extract powder.
  • Example 1 instead of pantethine, maltitol (“Resis” manufactured by Towa Kasei Kogyo Co., Ltd .: Comparative Example 1), mannitol (“Mannitol” manufactured by Saneigen FFI Co., Ltd .: Comparative Example 2) or sorbitol (Sorbitol (manufactured by San-Ei Gen FFI Co., Ltd.): Comparative Example 3) was used to produce a tablet in the same manner as in Example 1 except that mixing was performed at the blending ratios shown in Tables 4 to 6 below. Hardness was measured. Maltitol, mannitol and sorbitol are usually used as binders. The results of the average value of 10 tablets for each formulation are shown in Tables 4-6.
  • Formulation Examples 1-36 According to Formulation Examples 1 to 36, tablets were produced by a conventional method.

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Abstract

Disclosed is a tablet which contains a Kanpo herbal medicine and which has excellent mechanical strength and disintegrating properties. Specifically disclosed is a tablet comprising at least one Kanpo herbal medicine selected from the group consisting of 'Bofu-tsusho-san', 'Dai-sai-kokyo-daio-to', 'Boi-ogi-to' and 'Dai-saiko-to' and at least one pantethine component selected from pantethine, a salt of pantethine, pantothenic acid, a salt of pantothenic acid, pantetheine and panthenol.

Description

漢方薬およびパンテチン類を含有する錠剤Tablets containing herbal medicine and panthetins
　本発明は、所望の機械的強度および崩壊性を有する、漢方薬を含有する錠剤に関する。 The present invention relates to a tablet containing a Chinese medicine having desired mechanical strength and disintegration.
　一般的に、錠剤は１個の計量単位として摂取し易く、服用が容易であり、その製法も比較的容易であるなどの理由から、多くの医薬品、健康食品等に利用されている。錠剤は、製錠された後、包装されて輸送されるが、この過程で相当の振動、衝撃等の外力を受けるので、その商品価値を維持するため、錠剤が崩壊しないように適当な機械的強度（硬度）を有するように製錠しなければならない。 Generally, tablets are used in many pharmaceuticals, health foods, and the like because they are easy to take as one unit of measurement, are easy to take, and are relatively easy to manufacture. Tablets are packaged and then transported after being tableted. In this process, the tablet is subjected to considerable external forces such as vibration and impact. It must be tableted to have strength (hardness).
　また一方で、内服薬などの場合、服用後一定時間で崩壊しなければ効果が発揮されない。このため、硬度を高めるとともに、適度な崩壊性を錠剤に付与することが必要となる。 On the other hand, in the case of internal medicine etc., the effect will not be exhibited unless it disintegrates within a certain time after taking. For this reason, it is necessary to increase hardness and to impart appropriate disintegration properties to the tablet.
　錠剤の硬度を高める手段の一つとして、打錠圧を上げることが知られている（非特許文献１）。しかしながら、種々の漢方薬の製錠において、過剰な打錠圧は打錠時のキャッピング（錠剤上面の剥離）、ラミネーション（層状の剥離）等の原因となるので望ましくない。そればかりか、硬度を高めることで、崩壊性が低下してしまうという大きな問題が生じていた。 As one means for increasing the hardness of tablets, it is known to increase tableting pressure (Non-patent Document 1). However, in tableting various Chinese medicines, excessive tableting pressure is undesirable because it causes capping (peeling of the upper surface of the tablet), lamination (lamellar peeling), and the like during tableting. In addition to that, there is a big problem that the disintegration is lowered by increasing the hardness.
　錠剤の崩壊性を向上させる手段として、（１）デンプンやセルロース類などの崩壊剤の添加、（２）酸塩基反応による発泡作用の利用（発泡剤の添加）、（３）滑沢剤の微量化（外部滑沢）が知られている（非特許文献２および３）。しかし、錠剤は１錠あたりの原料の配合量がある程度限られているので、“崩壊剤や発泡剤の添加”は、有効成分などの配合量を低下させてしまう点が、また、“滑沢剤の微量化”では得られる効果が小さいという点が問題であった。 As means for improving the disintegration of tablets, (1) Addition of disintegrants such as starch and cellulose, (2) Use of foaming action by acid-base reaction (addition of foaming agent), (3) Trace amount of lubricant (External lubrication) is known (Non-Patent Documents 2 and 3). However, since the blending amount of raw materials per tablet is limited to some extent, “adding disintegrants and foaming agents” reduces the blending amount of active ingredients and the like. The problem is that the effect obtained by “miniaturization of the agent” is small.
　このため、錠剤の硬度を高めるとともに、崩壊性も向上できる方法が求められていた。
医薬品開発基礎講座Ｘ・製錠工学、地人書館、156頁、1971年 すぐに役立つ粒子設計・加工技術、じほう、221頁、2003年 Pharm. Tech. Japan, 第14巻、第11号、111頁、1998年 For this reason, there has been a demand for a method capable of increasing the hardness of the tablet and improving the disintegration property.
Pharmaceutical Development Basic Course X, Tablet Engineering, Jinshokan, 156, 1971 Immediately useful particle design and processing technology, Jiho, 221 pages, 2003 Pharm. Tech. Japan, Vol. 14, No. 11, p. 111, 1998
　そこで、本発明は、機械的強度および崩壊性の点で優れた効果を有する漢方薬を含有する錠剤を提供することを目的とする。 Therefore, an object of the present invention is to provide a tablet containing a Chinese medicine having an excellent effect in terms of mechanical strength and disintegration.
　本発明者は、漢方薬および錠剤を構成する他の全てまたは一部の材料を混合し、当該混合物を造粒して顆粒とし、その後、常法により打錠し、錠剤を製造した。また、本発明者は、錠剤を構成する全ての材料を混合し、その後、得られた混合物を常法により直接打錠し、錠剤を製造した。この場合、前者の造粒工程を経て製錠された錠剤は、造粒工程を経ることなく直接製錠された後者の錠剤と比較して硬度が高く、したがって製造方法を変更することで錠剤強度の改善が認められた。しかしながら、前記錠剤の場合であっても、商品として流通に耐え得る錠剤としては、なお不充分であった。 The present inventor mixed all or part of herbal medicine and other ingredients constituting the tablet, granulated the mixture into granules, and then tableted by a conventional method to produce tablets. In addition, the inventor mixed all the materials constituting the tablet, and then directly tableted the obtained mixture by a conventional method to produce a tablet. In this case, the tablet that was tableted through the former granulation process has higher hardness than the latter tablet that was directly tableted without going through the granulation process, and therefore the tablet strength can be changed by changing the manufacturing method. Improvement was observed. However, even in the case of the tablet, it is still insufficient as a tablet that can endure distribution as a commercial product.
　また、本発明者は、漢方薬に公知の賦形剤であるコーンスターチなどのデンプン類、乳糖、ショ糖などの糖類、でん粉のりやヒドロキシプロピルセルロースなどの結合剤を添加し、従来の方法により錠剤の製造を多数試みた。しかしながら、この場合も硬度および崩壊性の点で満足のいくものではなかった。 In addition, the present inventor added starches such as corn starch, which are known excipients for traditional Chinese medicine, sugars such as lactose and sucrose, binders such as starch paste and hydroxypropylcellulose, and the like. I tried a lot of manufacturing. However, even in this case, the hardness and disintegration were not satisfactory.
　本発明者は、上記課題に鑑み鋭意研究を重ねたところ防風通聖散、大柴胡去大黄湯、防已黄耆湯または大柴胡湯とパンテチン類を含有させることによって、硬度が向上され、かつ崩壊時間が短縮された錠剤が得られることを見出した。すなわち、パンテチン類には、漢方薬を含有する錠剤の硬度を向上させ、かつ崩壊時間を短縮できる効果があると考えられる。本発明は上記知見に基づきさらに検討を重ねた結果完成されたものであり、下記に掲げるものである。
（１）錠剤
（１－１）防風通聖散、大柴胡去大黄湯、防已黄耆湯および大柴胡湯からなる群より選択される少なくとも１種の漢方薬、ならびにパンテチン、パンテチンの塩、パントテン酸、パントテン酸の塩、パンテテインおよびパンテノールから選択される少なくとも１種のパンテチン類を含有する錠剤。
（１－２）錠剤の垂直方向の硬度が６Ｎ以上である、上記（１－１）に記載の錠剤。
（２）硬度向上剤、崩壊性向上剤
（２－１）パンテチン、パンテチンの塩、パントテン酸、パントテン酸の塩、パンテテインおよびパンテノールから選択される少なくとも１種のパンテチン類を有効成分とする、防風通聖散、大柴胡去大黄湯、防已黄耆湯および大柴胡湯からなる群より選択される少なくとも１種の漢方薬を含有する錠剤の硬度向上剤。
（２－２）パンテチン、パンテチンの塩、パントテン酸、パントテン酸の塩、パンテテインおよびパンテノールから選択される少なくとも１種のパンテチン類を有効成分とする、防風通聖散、大柴胡去大黄湯、防已黄耆湯および大柴胡湯からなる群より選択される少なくとも１種の漢方薬を含有する錠剤の崩壊性向上剤。
（２－３）パンテチン、パンテチンの塩、パントテン酸、パントテン酸の塩、パンテテインおよびパンテノールから選択される少なくとも１種のパンテチン類を有効成分とする、防風通聖散、大柴胡去大黄湯、防已黄耆湯および大柴胡湯からなる群より選択される少なくとも１種の漢方薬を含有する錠剤の硬度及び崩壊性向上剤。
（３）硬度向上方法、崩壊性向上方法
（３－１）防風通聖散、大柴胡去大黄湯、防已黄耆湯および大柴胡湯からなる群より選択される少なくとも１種の漢方薬と、パンテチン、パンテチンの塩、パントテン酸、パントテン酸の塩、パンテテインおよびパンテノールから選択される少なくとも１種のパンテチン類とを併用する、上記漢方薬を含有する錠剤の硬度向上方法。
（３－２）防風通聖散、大柴胡去大黄湯、防已黄耆湯および大柴胡湯からなる群より選択される少なくとも１種の漢方薬と、パンテチン、パンテチンの塩、パントテン酸、パントテン酸の塩、パンテテインおよびパンテノールから選択される少なくとも１種のパンテチン類とを併用する、上記漢方薬を含有する錠剤の崩壊性向上方法。
（３－３）防風通聖散、大柴胡去大黄湯、防已黄耆湯および大柴胡湯からなる群より選択される少なくとも１種の漢方薬と、パンテチン、パンテチンの塩、パントテン酸、パントテン酸の塩、パンテテインおよびパンテノールから選択される少なくとも１種のパンテチン類とを併用する、上記漢方薬を含有する錠剤の硬度及び崩壊性向上方法。 The present inventor has conducted extensive research in view of the above-mentioned problems, and the hardness is improved by containing Fufutsu Seisaku, Daisaikoku Daihoyu, Hosai Kotoyu or Daishibayu and panthetin, and It has been found that tablets with a reduced disintegration time can be obtained. That is, it is considered that pantethines have the effect of improving the hardness of tablets containing Chinese medicine and shortening the disintegration time. The present invention has been completed as a result of further studies based on the above findings, and is described below.
(1) Tablet (1-1) At least one herbal medicine selected from the group consisting of Fufutsu Seisaku, Daishiba-ku Daiho-to, Hosai-ko-to and Dai-saiko-to, and pantethine, pantethine salt, pantothene A tablet containing at least one panthetin selected from acids, salts of pantothenic acid, pantethein and panthenol.
(1-2) The tablet according to (1-1), wherein the tablet has a vertical hardness of 6N or more.
(2) Hardness improver, disintegration improver (2-1) Panthetin, pantethine salt, pantothenic acid, pantothenic acid salt, pantethein and panthenol are used as an active ingredient, A tablet hardness improving agent containing at least one Chinese herbal medicine selected from the group consisting of Fukatsutsu Seisaku, Daisaikoku Daihoto, Hosaikouyuto, and Daisaikoto.
(2-2) Pantethine, pantethine salt, pantothenic acid, pantothenic acid salt, pantethein and panthenol, at least one pantethine selected as an active ingredient, A disintegration improver for tablets containing at least one Chinese herb selected from the group consisting of Kosai Houyu-to and Dai-saiko-to.
(2-3) Panthetin, pantethine salt, pantothenic acid, pantothenic acid salt, pantethein and panthenol, at least one pantethine selected as an active ingredient, A tablet hardness and disintegration improver containing at least one Chinese herbal medicine selected from the group consisting of Kosai Houyu-to and Dai-saiko-to.
(3) Hardness improvement method, disintegration improvement method (3-1) at least one Chinese herbal medicine selected from the group consisting of Fukatsutsu Seisaku, Daishiba-ku-Dai-Yo-to, Ho-Kai-Dao-yu and Dai-saiko-to, A method for improving the hardness of a tablet containing the above-mentioned Chinese medicine, which is used in combination with at least one type of pantethine selected from pantethine, a salt of pantethine, pantothenic acid, a salt of pantothenic acid, pantethein and panthenol.
(3-2) At least one herbal medicine selected from the group consisting of Fufutsu Seisaku, Daisaikoku Daioyu, Hosaihoyuto, and Daisaikoto, and pantethine, pantethine salt, pantothenic acid, pantothenic acid A method for improving the disintegration of a tablet containing the above-mentioned Chinese medicine, which is used in combination with at least one kind of panthetin selected from a salt of the above, pantethein and panthenol.
(3-3) At least one herbal medicine selected from the group consisting of Fufutsu Seisaku, Daisaikoku Daihoyu, Hosaihoyuto, and Daisaikoto, and pantethine, pantethine salt, pantothenic acid, pantothenic acid A method for improving the hardness and disintegration of a tablet containing the above-mentioned Chinese herb medicine, which is used in combination with at least one kind of pantethine selected from the salts of:
　本発明の錠剤は、製錠されてから服用するまでに受ける振動や衝撃などの外力に十分に耐えることが可能な機械的強度を有する。また、本発明の錠剤は、服用後一定時間で崩壊する適度な崩壊性を有する。 The tablet of the present invention has a mechanical strength that can sufficiently withstand external forces such as vibration and impact received from tableting to taking. Moreover, the tablet of this invention has moderate disintegration which disintegrates in a fixed time after taking.
　また、本発明の錠剤によれば、配合される漢方薬およびパンテチン類に基づいて、その漢方薬特有の効能、およびパンテチン類由来のコレステロールに対する効果や腸の蠕動運動を活発化させる効果を、同時に得ることができる。 In addition, according to the tablet of the present invention, based on the herbal medicine and panthetin compounded, the effects specific to the traditional Chinese medicine, the effect on cholesterol derived from panthetin and the effect of activating peristaltic movement of the intestine can be obtained simultaneously. Can do.
　また、パンテチン類を有効成分とする本発明の硬度および／または崩壊性向上剤によれば、漢方薬を含有する錠剤において、その機械的強度を高くでき、また崩壊時間を短縮させることができる。 In addition, according to the hardness and / or disintegration improver of the present invention containing pantethine as an active ingredient, the mechanical strength can be increased and the disintegration time can be shortened in tablets containing Chinese medicine.
　また、本発明の硬度および／または崩壊性向上方法によれば、漢方薬を含有する錠剤においてその機械的強度を高くでき、また崩壊時間を短縮させることができ、所望の効果を有する錠剤を得ることができる。 In addition, according to the method for improving hardness and / or disintegration of the present invention, in a tablet containing Chinese medicine, the mechanical strength can be increased, the disintegration time can be shortened, and a tablet having a desired effect can be obtained. Can do.
　本発明の錠剤は、特定の漢方薬およびパンテチン類を含有することを主な特徴とする。以下、本発明の構成について詳細に説明する。
（１）漢方薬
　本発明の錠剤に配合される漢方薬としては、防風通聖散、大柴胡去大黄湯、防已黄耆湯および大柴胡湯が挙げられる。漢方薬として、硬度および崩壊性に優れる点で、好ましくは防風通聖散および大柴胡湯である。本発明において漢方薬はエキス形態またはエキス末形態である。本発明において漢方薬は、好ましくはエキス末形態である。本発明において漢方薬は、単独で配合してもよく、複数組み合わせて配合してもよい。 The tablet of the present invention is mainly characterized by containing a specific Chinese medicine and panthetins. Hereinafter, the configuration of the present invention will be described in detail.
(1) Traditional Chinese Medicine Examples of the traditional Chinese medicines to be blended in the tablet of the present invention include Fufutsu Seisaku, Daisai Kodoku Daiho-to, Hosei Korei-to and Dai-saiko-to. As herbal medicines, Fufutsu Seisaku and Daisaikoto are preferred because they are excellent in hardness and disintegration. In the present invention, the Chinese medicine is in the form of extract or extract powder. In the present invention, the Chinese medicine is preferably in the form of an extract powder. In the present invention, Chinese medicines may be blended alone or in combination.
　本発明において使用し得る漢方薬の原料としては、具体的には、マオウ（Ｅｐｈｅｄｒａ　ｓｉｎｉｃａ　Ｓｔａｐｆ，Ｅｐｈｅｄｒａ　ｉｎｔｅｒｍｅｄｉａ　Ｓｃｈｒｅｎｋ　ｅｔ　Ｃ．Ａ．　Ｍｅｙｅｒ，Ｅｐｈｅｄｒａ　ｅｑｕｉｓｅｔｉｎａ　Ｂｕｎｇｅ）、カンゾウ（Ｇｌｙｃｙｒｒｈｉｚａ　ｕｒａｌｅｎｓｉｓ　Ｆｉｓｃｈｅｒ，Ｇｌｙｃｙｒｒｈｉｚａ　ｇｌａｂｒａ　Ｌｉｎｎｅ）、ショウキョウ（Ｚｉｎｇｉｂｅｒ　ｏｆｆｉｃｉｎａｌｅ　Ｒｏｓｃｏｅ）、ケイガイ（Ｓｃｈｉｚｏｎｅｐｅｔａ　ｔｅｎｕｉｆｏｌｉａ　Ｂｒｉｑｕｅｔ）、レンギョウ（Ｆｏｒｓｙｔｈｉａ　ｓｕｓｐｅｎｓｅ　Ｖａｈｌ，　Ｆｏｒｓｙｔｈｉａ　ｖｉｒｉｄｉｓｓｉｍａ　Ｌｉｎｄｌｅｙ）、トウキ（Ａｎｇｅｌｉｃａ　ａｃｕｔｉｌｏｂａ　Ｋｉｔａｇａｗａ，　Ａｎｇｅｌｉｃａ　ａｃｕｔｉｌｏｂａ　Ｋｉｔａｇａｗａ　ｖａｒ．　ｓｕｇｉｙａｍａｅ　Ｈｉｋｉｎｏ）、シャクヤク（Ｐａｅｏｎｉａ　ｌａｃｔｉｆｌｏｒａ　Ｐａｌｌａｓ）、センキュウ（Ｃｎｉｄｉｕｍ　ｏｆｆｉｃｉｎａｌｅ　Ｍａｋｉｎｏ）、サンシン（Ｇａｒｄｅｎｉａ　ｊａｓｍｉｎｏｉｄｅｓ　Ｅｌｌｉｓ）、ハッカ（Ｍｅｎｔｈａ　ａｒｖｅｎｓｉｓ　Ｌｉｎｎｅ　ｖａｒ．　ｐｉｐｅｒａｓｃｅｎｓ　Ｍａｌｉｎｖａｕｄ）、ボウフウ（Ｓａｐｏｓｈｎｉｋｏｖｉａ　ｄｉｖａｒｉｃａｔａ　Ｓｃｈｉｓｃｈｋｉｎ）、ダイオウ（Ｒｈｅｕｍ　ｐａｌｍａｔｕｍ　Ｌｉｎｎｅ，　Ｒｈｅｕｍ　ｔａｎｇｕｔｉｃｕｍ　Ｍａｘｉｍｏｗｉｃｚ，　Ｒｈｅｕｍ　ｏｆｆｉｃｉｎａｂｌｅ　Ｂａｉｌｌｏｎ，　Ｒｈｅｕｍｃｏｒｅａｎｕｍ　Ｎａｋａｉまたはそれらの種間雑種）、ビャクジュツ（Ａｔｒａｃｔｙｌｏｄｅｓ　ｊａｐｏｎｉｃａ　Ｋｏｉｄｚｕｍｉ　ｅｘ　Ｋｉｔａｍｕｒａ，　Ａｔｒａｃｔｙｌｏｄｅｓ　ｏｖａｔａ　Ｄｅ　Ｃａｎｄｏｌｌｅ）、キキョウ（Ｐｌａｔｙｃｏｄｏｎ　ｇｒａｎｄｉｆｌｏｒｕｍ　Ａ．　Ｄｅ　Ｃａｎｄｏｌｌｅ）、オウゴン（Ｓｃｕｔｅｌｌａｒｉａｅ　ｂａｉｃａｌｅｎｓｉｓ　Ｇｅｏｒｇｉ）、サイコ（Ｂｕｐｌｅｕｒｕｍ　ｆａｌｃａｔｕｍ　Ｌｉｎｎｅ）、ハンゲ（Ｐｉｎｅｌｌｉａ　ｔｅｒｎａｔａ　Ｂｒｅｉｔｅｎｂａｃｈ）、タイソウ（Ｚｉｚｙｐｕｓ　ｊｕｊｕｂｅ　Ｍｉｌｌｅｒ　ｖａｒ．　ｉｎｅｒｍｉｓ　Ｒｅｈｄｅｒ）、キジツ（Ｃｉｔｒｕｓ　ａｕｒａｎｔｉｕｍ　Ｌｉｎｎｅ　ｖａｒ．　ｄａｉｄａｉ　Ｍａｋｉｎｏ，　Ｃｉｔｒｕｓ　ａｕｒａｎｔｉｕｍ　Ｌｉｎｎｅ，　Ｃｉｔｒｕｓ　ｎａｔｓｕｄａｉｄａｉ　Ｈａｙａｔａ）、ボウイ（Ｓｉｎｏｍｅｎｉｕｍ　ａｃｕｔｕｍ　Ｒｅｈｄｅｒ　ｅｔ　Ｗｉｌｓｏｎ）、オウギ（Ａｓｔｒａｇａｌｕｓ　ｍｅｍｂｒａｎａｃｅｕｓ　Ｂｕｎｇｅ，　Ａｓｔｒａｇａｌｕｓ　ｍｏｎｇｈｏｌｉｃｕｓ　Ｂｕｎｇｅ）、ジュツ（Ａｔｒａｃｔｙｌｏｄｅｓ　ｌａｎｃｅａ　Ｄｅ　Ｃａｎｄｏｌｌｅ，　Ａｔｒａｃｔｙｌｏｄｅｓｃｈｉｎｅｎｓｉｓ　Ｋｏｉｄｚｕｍｉ）、ボウショウ（芒硝：硫酸ナトリウム）、カッセキ（滑石：天然含水ケイ酸アルミニウムおよび二酸化ケイ素含有物）およびセッコウ（石膏：含水硫酸カルシウム）である。 Specific examples of herbal medicines that can be used in the present invention include maph (Ephedra sinaica Stapf, Ephedra intermedia schlenk et CA. Meyer, Ephedra equisetina Bunge), and licorice (GlyzrhisrlyglysirFlysr. Kyo (Zingiber officinale Roscoe), Kaigai (Schizonepeta tenuifolia Briquet), Forsythia suspense Vahl, Forsythia viridissimilarisindimilidisimidalysidimaisiridaisimidalysidimaisiridaisimidalysidimaisiridaisimidalysidimaisiramidilesimilaridsimilamisiramidilesidis tiloba Kitagawa, Angelica acutiloba Kitagawa var. sugiyamae Hikino), peony (Paeonia lactiflora Pallas), Sinensis (Cnidium officinale Makino), Sanshin (Gardenia jasminoides Ellis), peppermint (Mentha arvensis Linne var. piperascens Malinvaud), storm (Saposhnikovia divaricata Schischkin) , Rheum palmatum Linne, Rheum tanguticum Maximowicz, Rheum officin ble Baillon, Rheumcoreanum Nakai or their interspecific hybrids), Byakujutsu (Atractylodes japonica Koidzumi ex Kitamura, Atractylodes ovata De Candolle), bellflower (Platycodon grandiflorum A. De Candolle), Scutellaria (Scutellariae baicalensis Georgi), Psycho (Bupleurum falcatum Linne) , Hange (Pinella ternata Breitenbach), Tizou (Zizypus jujube Miller var. Inertis Rehder), Kisetsu (Citrus) Aurantium Linne var. daidai Makino, Citrus aurantium Linne, Citrus natsudaidai Hayata), Bowie (Sinomenium acutum Rehder et Wilson), Astragali (Astragalus membranaceus Bunge, Astragalus mongholicus Bunge), the predicate (Atractylodes lancea De Candolle, Atractylodeschinensis Koidzumi), of sodium sulfate (Glauber's salt: sodium sulfate) Kasseki (talc: natural hydrous aluminum silicate and silicon dioxide containing) and gypsum (gypsum: hydrous calcium sulfate).
　上記漢方薬は、下記表１に示す原料から得られる。 The above Chinese herbal medicine is obtained from the raw materials shown in Table 1 below.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
　表中、＊は任意成分を表す。 * In the table, * represents an optional component.
　これらの原料のうち、植物原料は、日本薬局方に準じて使用部位が規定されている。 Of these raw materials, plant raw materials have specified use sites according to the Japanese Pharmacopoeia.
　本発明において使用し得る漢方薬（防風通聖散、大柴胡去大黄湯、防已黄耆湯および大柴胡湯）の調製は、「一般用漢方処方の手引き」（厚生省薬務局監修、日薬連漢方専門委員会編集、薬業時報社発行）に準じて行い得る。 The preparation of Kampo medicines that can be used in the present invention (Futsutsu Seisan, Daishiba-ku Daiho-to, Hosai-Houyu-to and Dai-saiko-to) is “Guide to General Kampo Prescription” (supervised by the Ministry of Health and Welfare (Edited by the National Chinese Medicine Special Committee, published by Yakuho Jihosha).
　本発明において使用される上記漢方薬には、漢方生薬調査会により定められた「漢方製剤の基本的取扱い方針」に規定されるように、現在繁用されている漢方関係の書簡に記載されている漢方処方（生薬配合物）やこれらの漢方処方から得られるエキスが包含される。本発明において、漢方薬は得られたエキス（エキス形態）を使用してもよく、エキスを常法により製剤化した、いわゆるエキス末（エキス末形態）を使用してもよい。 The above-mentioned Kampo medicine used in the present invention is described in the Chinese medicine-related letters currently in use as defined in the “Basic Handling Policy of Kampo Preparations” established by the Kampo Herbal Medicine Research Committee. Herbal prescriptions (herbal medicine blends) and extracts obtained from these Chinese herbal prescriptions are included. In the present invention, the Chinese herbal medicine may use the obtained extract (extract form) or a so-called extract powder (extract powder form) obtained by formulating the extract by a conventional method.
　かかるエキス末の製造方法としては、例えば、上記各成分の混合物に対し、約１０～２０倍量の水を加え、８０～１００℃程度で１～３時間程度撹拌抽出し、温時遠心分離もしくは、ろ過して抽出液を得、これを減圧下に濃縮し、スプレードライ法により乾燥エキス末とするか、或いはエキスの濃度を高めた軟エキスに適当な吸着剤（例えば無水ケイ酸、デンプン等）を加えて吸着エキス末とする方法が挙げられる。 As a method for producing such extract powder, for example, about 10 to 20 times the amount of water is added to the mixture of the above components, and the mixture is stirred and extracted at about 80 to 100 ° C. for about 1 to 3 hours. , Filtered to obtain an extract, which is concentrated under reduced pressure and made into a dry extract powder by a spray drying method, or an adsorbent suitable for a soft extract with an increased concentration of the extract (eg, silicic anhydride, starch, etc.) ) To obtain an adsorbent extract powder.
　漢方薬のうち、例えば、防風通聖散は、原料の乾燥重量換算にて、トウキ１．２（重量部、以下同じ）、シャクヤク１．２、センキュウ１．２、サンシシ１．２、レンギョウ１．２、ハッカ１．２、ショウキョウ１．２、ケイガイ１．２、ボウフウ１．２、マオウ１．２、ダイオウ１．５、ボウショウ１．５、ビャクジュツ２．０、キキョウ２．０、オウゴン２．０、カンゾウ２．０、セッコウ２～３およびカッセキ３～５を、その２０倍重量（従って５６０～６２０重量部）の湯で抽出した後、１／２容量になるまで濃縮し、固形分を除いたものをエキスとして使用でき、このエキスからエキス末が製造される。 Among the Chinese herbal medicines, for example, Fukatsutsu Seisan is converted to dry weight of raw materials, such as Toki 1.2 (parts by weight, hereinafter the same), Peonies 1.2, Senkyu 1.2, Sanshi 1.2, Forsythia 1. 2, mint 1.2, show 1.2, kei guy 1.2, bow 1.2, maow 1.2, dio 1.5, bow show 1.5, peacock 2.0, kyo 2.0, oggon 2 0.0, Licorice 2.0, Gypsum 2-3 and Kasseki 3-5 are extracted with 20 times their weight (and hence 560-620 parts by weight) of hot water, then concentrated to 1/2 volume, The extract powder can be used as an extract, and an extract powder is produced from this extract.
　ここで、書簡によっては、上記成分中、ビャクジュツを含まないもの（例えば「経験漢方処方分量集」、大塚敬節・矢数道明監集、医道の日本社発行、１９９３年）、オウゴンを含まないもの（例えば、「続漢方あれこれ」大阪読売新聞社編、浪速社発行、昭和１９６８年）、上記分量中、１．２をすべて１．５としているもの（例えば「明解漢方処方」、西岡一夫、高橋真太郎共著、浪速社発行、１９６６年）など、成分や成分比が多少異なるものもある。 Here, some letters do not contain peanuts in the above ingredients (for example, “Experienced Kampo Prescription Quantity Collection”, Takatsuka Otsuka and Michiaki Yahaji, published by Nippon Shokudo Inc., 1993), Ogon Items (for example, “Sequential Kampo this and that” edited by Osaka Yomiuri Shimbun, published by Naniwasha, 1968), those in which 1.2 is 1.5 in all the above quantities (for example, “Meiden Kampo prescription”, Kazuo Nishioka, Some of the ingredients and component ratios are slightly different, such as coauthored by Shintaro Takahashi, published by Naniwasha, 1966).
　また、防風通聖散の製造方法についても、ボウショウ以外の上記各成分に水４００重量部を加え、２００重量部まで煎じて、カスを除き、次いでボウショウを加えるとしているもの（例えば「和漢薬ハンドブック」、久保道徳、森山健三共著、保育社発行、１９９５年）など、作り方が上記と多少異なるものがある。 In addition, as for the method for producing Fukatsutsu Seisaku, 400 parts by weight of water is added to each of the above components other than bowsho, decocted to 200 parts by weight, the residue is removed, and then bowsho is added (for example, “Wakan Handbook” ”, Michinori Kubo, Kenzo Moriyama, published by Yoikusha, 1995), etc.
　本発明においては、これらの差異は特に制限されず、いずれも防風通聖散として包含される。 In the present invention, these differences are not particularly limited, and any of these differences are included as a windproof sansho.
　例えば、本発明に使用可能な防風通聖散エキス末は、前述のとおり製造することが可能であるが、例えば、防風通聖散乾燥エキスＡ、防風通聖散乾燥エキスＡＭ、防風通聖散乾燥エキスＥおよび防風通聖散乾燥エキスＥＭ（いずれも日本粉末株式会社製）ならびに防風通聖散料乾燥エキス－Ｃおよび防風通聖散料乾燥エキス－Ｆ（いずれもアルプス薬品工業株式会社製）等の商品が知られており、商業的に入手することもできる。 For example, the wind-proof scented powder extract that can be used in the present invention can be produced as described above. Dried extract E and Fufutsu Seisan dried extract EM (both manufactured by Nihon Powder Co., Ltd.), and Fufutsu Seikoku dried extract-C and Fufutsu Seikoku dried extract-F (both manufactured by Alps Pharmaceutical Co., Ltd.) Such products are known and can be obtained commercially.
　漢方薬のうち、例えば、大柴胡湯は、原料の乾燥重量換算にて、サイコ６．０（重量部、以下同じ）、ハンゲ３．０～４．０、ショウキョウ４．０～５．０、オウゴン３．０、シャクヤク３.０、タイソウ３．０、キジツ２．０、ダイオウ１．０～２．０とされており、原則として、これを、その２０倍重量（従って５００～５６０重量部）の湯で抽出した後、１／２容量になるまで濃縮し、固形分を除いたものエキスとして使用でき、このエキスからエキス末が製造される。 Among the traditional Chinese medicines, for example, Dai-saiko-to is Psycho 6.0 (parts by weight, the same applies hereinafter), Hange 3.0-4.0, Showa 4.0-5.0, Ogon 3.0, Peonies 3.0, Taiso 3.0, Pheasant 2.0, Daio 1.0-2.0, and in principle, this is 20 times the weight (thus 500-560 parts by weight). ) And then concentrated to 1/2 volume, and can be used as an extract from which solid content has been removed, and an extract powder is produced from this extract.
　なお、書簡によっては、成分や成分比、作り方が上記と多少異なるものもある。本発明においては、これらの差異は特に制限されず、いずれも上記各々の漢方薬として包含される。 Note that some letters may differ slightly from the above in terms of composition, composition ratio, and method. In the present invention, these differences are not particularly limited, and any of them is included as each of the above Chinese medicines.
　また、大柴胡去大黄湯エキス末、防已黄耆湯エキス末および大柴胡湯エキス末についても同様に製造することが可能であり、例えば、防已黄耆湯は、防已黄耆湯乾燥エキスＡおよび防已黄耆湯乾燥エキスＡＺ（いずれも日本粉末株式会社製）ならびに防已黄耆湯エキス末および防已黄耆湯乾燥エキス－Ｆ（いずれもアルプス薬品工業株式会社製）等が、大柴胡湯は、大柴胡湯乾燥エキス、大柴胡湯乾燥エキスＡＭ、大柴胡湯乾燥エキスＳＮおよび大柴胡湯乾燥エキス粉末（いずれも日本粉末株式会社製）ならびに大柴胡湯乾燥エキスＦおよび大柴胡湯乾燥エキス－Ｆ（いずれもアルプス薬品工業製）等の商品が知られており、商業的に入手することもできる。 In addition, it is also possible to produce Daisaikou Daioyu extract powder, Hosai Koyuto extract powder and Daisaikoyu extract powder, for example, Extract A and Housui-Kyuto dry extract AZ (both manufactured by Nihon Powder Co., Ltd.), Houho Kyo-yu extract powder and Hou-Kou Kouyu dried extract-F (both manufactured by Alps Pharmaceutical Co., Ltd.), etc. Daisaikou, Daisaikoto dry extract, Daisaikoto dry extract AM, Daisaikoto dry extract SN and Daisaikoto dry extract powder (all manufactured by Nippon Powder Co., Ltd.) and Daisaikoto dry extract F and Daishiba Products such as kuyu dried extract-F (all manufactured by Alps Pharmaceutical Co., Ltd.) are known and can also be obtained commercially.
　本発明の錠剤における漢方薬の配合割合は、本発明の効果が奏される限りとくに限定されないが、例えば、錠剤中に、通常、エキスの乾燥重量総量またはエキス末総量で０．０１～９８重量％程度、好ましくは０．１～９５重量％程度、より好ましくは１～９０重量％程度である。 The blending ratio of the Chinese medicine in the tablet of the present invention is not particularly limited as long as the effect of the present invention is exhibited. For example, the total dry weight of the extract or the total amount of the extract powder is usually 0.01 to 98% by weight in the tablet. About 0.1 to 95% by weight, more preferably about 1 to 90% by weight.
　漢方薬として、とくに防風通聖散および／または大柴胡湯を用いる場合は、その配合割合は錠剤中に、通常、総量で０．１～９８重量％程度、好ましくは１～９５重量％程度、より好ましくは３～９０重量％程度、さらに好ましくは１０～９０重量％程度、とくに好ましくは３０～８０重量％程度である。ほかの漢方薬を用いる場合には、その配合量は、前記防風通聖散の配量合を参考に本願発明の効果を奏するように適宜設定することができる。
（２）パンテチン類
　本発明の錠剤は、上記漢方薬とパンテチン類とを含有することを特徴とする。 When Fufutsu Seisaku and / or Dai-saiko-to is used as a traditional Chinese medicine, the blending ratio is usually about 0.1 to 98% by weight, preferably about 1 to 95% by weight in the tablet. The amount is preferably about 3 to 90% by weight, more preferably about 10 to 90% by weight, particularly preferably about 30 to 80% by weight. In the case of using other Chinese medicines, the blending amount can be appropriately set so that the effect of the present invention can be obtained with reference to the amount of the above-mentioned Fukatsutsu Seisan.
(2) Panthetins The tablet of the present invention is characterized by containing the above-mentioned Chinese medicine and panthetins.
　本発明においてパンテチン類としては、パンテチン、パントテン酸、パンテテイン、パンテノール、およびパンテチンまたはパントテン酸の塩からなる群から選択される少なくとも１種が挙げられる。パンテチンまたはパントテン酸の塩としては、薬学的に許容されるものであれば限定されず、例えばナトリウム塩、カリウム塩などのアルカリ金属塩、カルシウム塩、マグネシウム塩などのアルカリ土類金属、塩酸塩、硝酸塩、硫酸塩等の鉱酸塩、酢酸塩、クエン酸塩、安息香酸などの有機酸塩などを挙げることができる。これらのパンテチン類は類似の基本骨格を有している。 In the present invention, the pantethine includes at least one selected from the group consisting of pantethine, pantothenic acid, pantethein, panthenol, and a salt of pantethine or pantothenic acid. The salt of pantethine or pantothenic acid is not limited as long as it is pharmaceutically acceptable, for example, alkali metal salts such as sodium salt and potassium salt, alkaline earth metals such as calcium salt and magnesium salt, hydrochloride salt, Examples thereof include mineral acid salts such as nitrate and sulfate, and organic acid salts such as acetate, citrate and benzoic acid. These panthetins have a similar basic skeleton.
　本発明の錠剤には、パンテチン類の中から選択された１種単独でまたは２種以上を組み合わせて配合される。本発明の錠剤に配合されるパンテチン類としては、パンテチンが好ましい。 In the tablet of the present invention, one kind selected from pantetins alone or a combination of two or more kinds is blended. As pantethine compounded in the tablet of the present invention, pantethine is preferable.
　パンテチン（Pantethine）は、ビス（２－{３－［（２Ｒ）－２，４－ジヒドロキシ－３，３－ジメチルブタノイルアミノ］プロパノイルアミノ}エチル）ジスルフィドとして表され、パントテン酸（ビタミンＢ５）誘導体または活性型ビタミンＢ５とも呼ばれる。 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.
　パンテチンは公知の化合物であり、従来公知の方法に従って合成することもできるが、パンテチンとしては例えば「パンテチンＡ」（第一三共プロファーマ製）等の商品も知られており、商業的に入手することもできる。パンテチン以外のパンテチン類も公知であり、従来の方法に従って得ることができ、また市販のものを用いることもできる。 Pantethine is a known compound and can be synthesized according to a conventionally known method, but as pantethine, for example, a product such as “Panthetine A” (manufactured by Daiichi Sankyo Propharma) is also known and commercially available. You can also Panthetins other than pantethine are also known and can be obtained according to conventional methods, and commercially available products can also be used.
　本発明の錠剤におけるパンテチン類の配合割合は、本発明の効果が奏される限りとくに限定されないが、例えば、錠剤中に、通常、パンテチン量換算で０．０１～９５重量％程度、好ましくは０．１～８０重量％程度、より好ましくは０．１～４０重量％程度である。 The blending ratio of panthetins in the tablet of the present invention is not particularly limited as long as the effects of the present invention are exerted. For example, in a tablet, it is usually about 0.01 to 95% by weight in terms of pantethine, preferably 0 About 1 to 80% by weight, more preferably about 0.1 to 40% by weight.
　パンテチン類として、とくにパンテチンを用いる場合は、その配合割合は錠剤中に、通常、総量で０．０１～９５重量％程度、好ましくは０．１～８０重量％程度、より好ましくは０．１～４０重量％程度である。
（３）漢方薬に対するパンテチン類の配合割合
　本発明の錠剤における、漢方薬に対するパンテチン類の配合割合は、本発明の効果を奏する限り限定されないが、漢方薬とパンテチン類の混合物が過剰にべたつくことなく、例えば、打錠時に使用する杵や臼に混合物が付着することなく錠剤を好適に製造でき、また、パンテチン類由来のコレステロールに対する効果や腸の蠕動運動を活発化させる効果などが損なわれず、かつ硬度および崩壊性の点で優れた錠剤が製造できることから、例えば、漢方薬の総量１００重量部に対するパンテチン類の総量の下限値は、好ましくは０．０１重量部であり、より好ましくは０．１重量部であり、さらに好ましくは０．１２５重量部であり、とくに好ましくは０．２重量部である。また、パンテチン類の総量の上限値は、好ましくは３０重量部であり、より好ましくは２８重量部であり、さらに好ましくは２５重量部である。 In particular, when pantethine is used as the pantethine, the blending ratio thereof is usually about 0.01 to 95% by weight, preferably about 0.1 to 80% by weight, more preferably 0.1 to 80% by weight in the tablet. About 40% by weight.
(3) Mixing ratio of pantethine to Chinese medicine The mixing ratio of pantethine to Chinese medicine in the tablet of the present invention is not limited as long as the effect of the present invention is exerted, but the mixture of Chinese medicine and panthetin is not excessively sticky, for example The tablet can be preferably produced without adhering the mixture to the pestle or mortar used for tableting, and the effect on panthetin-derived cholesterol and the effect of activating the peristaltic movement of the intestine are not impaired, and the hardness and Since a tablet excellent in disintegration can be produced, for example, the lower limit of the total amount of panthetins relative to 100 parts by weight of the traditional Chinese medicine is preferably 0.01 parts by weight, more preferably 0.1 parts by weight. More preferably 0.125 parts by weight, particularly preferably 0.2 parts by weight. Moreover, the upper limit of the total amount of panthetins is preferably 30 parts by weight, more preferably 28 parts by weight, and even more preferably 25 parts by weight.
　例えば、本発明の一実施形態について説明すると、漢方薬として防風通聖散および／または大柴胡湯を使用し、パンテチン類としてパンテチンを使用する場合、防風通聖散および／または大柴胡湯の総量１００重量部に対してパンテチンの総量の下限値は、好ましくは０．１重量部であり、より好ましくは１重量部であり、さらに好ましくは１．２５重量部であり、とくに好ましくは２重量部である。また、パンテチンの総量の上限値は、好ましくは３０重量部であり、より好ましくは２８重量部であり、さらに好ましくは２５重量部である。この範囲内であると、錠剤硬度、崩壊性および打錠時の臼・杵への付着の点で好ましい。
（４）錠剤の大きさ
　本発明の錠剤の大きさは本発明の効果を奏する限りとくに限定されないが、使用対象、使用目的等に応じて適宜調整される。例えば、本発明の錠剤の直径は服用しやすいサイズが例示され、好ましくは直径１８ｍｍ以下、より好ましくは１５ｍｍ以下、さらに好ましくは１２ｍｍ以下が例示される。また、本発明の錠剤の厚みも服用しやすいサイズが例示され、好ましくは直径１０ｍｍ以下、より好ましくは９ｍｍ以下、さらに好ましくは８ｍｍ以下が例示される。
（５）錠剤に含有可能なほかの成分
　本発明の錠剤には、例えば、担体として当該分野で従来公知のものを広く使用することができる。このような担体としては、例えば乳糖、白糖、塩化ナトリウム、ブドウ糖、尿素、デンプン、炭酸カルシウム、カオリン、ケイ酸等の賦形剤；水、エタノール、プロパノール、単シロップ、ブドウ糖液、デンプン液、ゼラチン溶液、カルボキシメチルセルロース、セラック、メチルセルロース、リン酸カリウム、ポリビニルピロリドン、結晶セルロース、ヒドロキシプロピルセルロース、ヒプロメロース、アルギン酸ナトリウム等の結合剤；乾燥デンプン、カンテン末、ラミナラン末、炭酸水素ナトリウム、ポリオキシエチレンソルビタン脂肪酸エステル類、ラウリル硫酸ナトリウム、ステアリン酸モノグリセリド、デンプン、クロスポビドン、ポビドン、低置換度ヒドロキシプロピルセルロース、等の崩壊剤；ステアリン、カカオバター、水素添加油等の崩壊抑制剤；第４級アンモニウム塩、ラウリル硫酸ナトリウム等の吸収促進剤；グリセリン等保湿剤；デンプン、乳糖、カオリン、ベントナイト、コロイド状ケイ酸等の吸着剤；精製タルク、ステアリン酸塩、ホウ酸末、ポリエチレングリコール等の滑沢剤等を使用できる。また、本発明の錠剤には、上記以外に、添加剤として、例えば界面活性剤、吸収促進剤、吸着剤、充填剤、防腐剤、安定剤、乳化剤、可溶化剤、浸透圧を調節する塩を含有させることができる。さらに、本発明の錠剤には、上記以外にアミノ酸、ビタミン類、有機酸塩類等の他の活性成分を含有させることができる。他の活性成分としては、例えば、バリン、ロイシン、イソロイシン、トレオニン、メチオニン、フェニルアラニン、トリプトファン、リジン、グリシン、アラニン、アスパラギン、グルタミン、セリン、システイン、シスチン、チロシン、プロリン、ヒドロキシプロリン、アスパラギン酸、グルタミン酸、ヒドロキシリジン、アルギニン、オルニチン、ヒスチジン等のアミノ酸；ビタミンＡ１、ビタミンＡ２、カロチン、リコピン（プロビタミンＡ）、ビタミンＢ６、ビタミンＢ１、ビタミンＢ２、アスコルビン酸、ニコチン酸アミド、ビオチン等のビタミン類；塩化ナトリウム、塩化カリウム等のアルカリ金属塩や、クエン酸塩、酢酸塩、リン酸塩等の有機酸塩類が例示される。 For example, when one embodiment of the present invention is described, when using Fukatsutsu Seisaku and / or Daisaikoto as a herbal medicine and Pantetin is used as pantetins, the total amount of Fukatsutsu Seisaku and / or Daisaikoto is 100. The lower limit of the total amount of pantethine with respect to parts by weight is preferably 0.1 parts by weight, more preferably 1 part by weight, still more preferably 1.25 parts by weight, particularly preferably 2 parts by weight. is there. The upper limit of the total amount of pantethine is preferably 30 parts by weight, more preferably 28 parts by weight, and even more preferably 25 parts by weight. Within this range, it is preferable in terms of tablet hardness, disintegration, and adhesion to the mortar and punch during tableting.
(4) Size of tablet The size of the tablet of the present invention is not particularly limited as long as the effect of the present invention is exhibited, but is appropriately adjusted according to the use object, purpose of use and the like. For example, the size of the tablet of the present invention is exemplified by a size that is easy to take, preferably 18 mm or less, more preferably 15 mm or less, and even more preferably 12 mm or less. Further, the size of the tablet of the present invention is exemplified by a size that can be easily taken, preferably 10 mm or less in diameter, more preferably 9 mm or less, and still more preferably 8 mm or less.
(5) Other components that can be contained in tablets For the tablets of the present invention, for example, those conventionally known in the art can be widely used as carriers. Examples of such 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, stearic acid monoglyceride, starch, crospovidone, povidone, low substituted hydroxypropylcellulose; stearin, cocoa butter, Disintegration inhibitors such as additive oils; Absorption accelerators such as quaternary ammonium salts and sodium lauryl sulfate; Moisturizers such as glycerin; Adsorbents such as starch, lactose, kaolin, bentonite, colloidal silicic acid; Purified talc, stearin Lubricants such as acid salts, boric acid powder and polyethylene glycol can be used. In addition to the above, the tablet of the present invention includes, for example, a surfactant, an absorption accelerator, an adsorbent, a filler, a preservative, a stabilizer, an emulsifier, a solubilizer, and a salt that adjusts osmotic pressure. Can be contained. Furthermore, in addition to the above, the tablet of the present invention may contain other active ingredients such as amino acids, vitamins, and organic acid salts. Other active ingredients include, for example, 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; Examples include alkali metal salts such as sodium chloride and potassium chloride, and organic acid salts such as citrate, acetate and phosphate.
　さらに錠剤は、必要に応じ通常の剤皮を施した錠剤、例えば糖衣錠、ゼラチン被包錠、腸溶被錠、フィルムコーティング錠あるいは二重錠、多層錠とすることができる。
（６）錠剤の製造方法
　本発明の錠剤の製造方法は、得られた錠剤が所望の効果を発揮できる限り限定されず、従来公知の方法に従い製造することができる。また、漢方薬およびパンテチン類の具体的な材料およびそれらの配合割合等は、前述の記載に従って適宜設定される。通常は、漢方薬とパンテチン類、およびその他、必要に応じて賦形剤等を混合して打錠すればよい。また、打錠については配合材料の全部を直接打錠してもよく、また打錠前に配合材料の一部または全部を顆粒状にしてそののちに打錠するなど、常法に従い打錠すればよい。
（７）錠剤の硬度および崩壊性
　本発明の錠剤の硬度は、本発明の効果を奏する限りとくに限定されないが、例えば、垂直方向の硬度が６Ｎ以上であることが好ましく、８Ｎ以上であることがより好ましく、１０Ｎ以上であることがさらに好ましい。 Further, 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.
(6) Manufacturing method of tablet The manufacturing method of the tablet of this invention is not limited as long as the obtained tablet can exhibit a desired effect, It can manufacture according to a conventionally well-known method. In addition, specific materials of Chinese herbal medicine and panthetin, their blending ratio, and the like are appropriately set according to the above description. Usually, it may be tableted by mixing Chinese medicine and pantethine, and other excipients if necessary. In addition, for tableting, all of the compounding material may be directly compressed, and if tableting is performed according to a conventional method, such as granulating part or all of the compounding material before tableting, and then tableting it. Good.
(7) Hardness and disintegration of tablet The hardness of the tablet of the present invention is not particularly limited as long as the effect of the present invention is exhibited. For example, the hardness in the vertical direction is preferably 6N or more, and preferably 8N or more. More preferably, it is more preferably 10N or more.
　本発明において錠剤の硬度は、木屋式デジタル硬度計ＫＨＴ－２０Ｎ型（株式会社藤原製作所）を用いて測定される。 In the present invention, the hardness of the tablet is measured using a Kiya type digital hardness meter KHT-20N type (Fujiwara Manufacturing Co., Ltd.).
　本発明の錠剤の崩壊性は、製造される錠剤の大きさ、形状、製錠時の圧力等により左右されるためこれらに応じて変更し得るので、本発明の効果を奏する限りとくに限定されないが、漢方薬単独からなる錠剤の崩壊時間（Ｔ０）に対する、漢方薬およびパンテチン類からなる錠剤の崩壊時間（ＴＸ）の割合の逆数、すなわち（Ｔ０／ＴＸ）にて評価される。 The disintegration property of the tablet of the present invention is not particularly limited as long as the effect of the present invention can be obtained because it can be changed according to the size, shape, pressure at the time of tableting, etc. The reversal of the disintegration time (T X ) of a tablet made of Chinese medicine and pantethine with respect to the disintegration time (T 0 ) of a tablet made of Chinese medicine alone is evaluated by the reciprocal of (T 0 / T X ).
　例えば、本発明の一実施形態について説明すると、漢方薬として防風通聖散および／または大柴胡湯を使用し、圧力２５Ｍｐａにて直径９ｍｍの凸型錠剤を打錠して錠剤を製造する場合、崩壊性の向上（崩壊時間の短縮）はとくに限定されないが、好ましくは５％以上、より好ましくは８％以上、さらに好ましくは１０％以上である。 For example, when an embodiment of the present invention is described, when Fengtsu Sansho and / or Dai-saiko-to is used as a traditional Chinese medicine and a convex tablet having a diameter of 9 mm is compressed at a pressure of 25 Mpa, the tablet is disintegrated. The improvement in property (reduction of disintegration time) is not particularly limited, but is preferably 5% or more, more preferably 8% or more, and further preferably 10% or more.
　錠剤の崩壊時間は、日本薬局方に記載の崩壊時間の測定法によって測定できるが、その他に適宜試験条件を設定し、水溶液中にて錠剤が崩壊する時間を測定すればよく、例えば、１００ｍｌビーカーに３７℃の水８０ｍｌをいれ、２ｃｍのスターラーバーを４００ｒｐｍにて回転させ、錠剤を投入してから錠剤が目視により観察できなくなるまでの時間を測定することでも可能である。 The disintegration time of the tablet can be measured by the disintegration time measurement method described in the Japanese Pharmacopoeia. However, other test conditions may be set as appropriate, and the disintegration time in the aqueous solution may be measured. For example, a 100 ml beaker It is also possible to add 80 ml of water at 37 ° C., rotate a 2 cm stirrer bar at 400 rpm, and measure the time from when the tablet is inserted until the tablet cannot be visually observed.
　本発明の錠剤の１日摂取量は、摂取対象に応じて適宜変更され得るが、例えば大人一人（体重６０ｋｇ）に対する投与量は、漢方薬のエキスの乾燥重量総量またはエキス末総量で通常０．０１～１２ｇ程度、好ましくは０．０５～１０ｇ程度、より好ましくは０．０７～８ｇ程度である。また、例えば漢方薬として防風通聖散を用いる場合は、エキスの乾燥重量総量またはエキス末総量で、通常０．１～１０ｇ程度、好ましくは１．０～８ｇ程度、より好ましくは１．５～６ｇ程度である。また、本発明の医薬組成物は、通常一日２～３回に分けて経口投与の形態で用いられる。服用時刻は、特に限定されないが、食前または食間が好ましい。
（８）硬度向上剤、崩壊性向上剤
　本発明の錠剤の硬度向上剤は、パンテチン、パンテチンの塩、パントテン酸、パントテン酸の塩、パンテテインおよびパンテノールから選択される少なくとも１種のパンテチン類を有効成分とするものであり、防風通聖散、大柴胡去大黄湯、防已黄耆湯および大柴胡湯からなる群より選択される少なくとも１種の漢方薬を含有する錠剤の硬度を高めることができる。パンテチン類および漢方薬の具体的な材料およびそれらの配合割合等は、前述の記載に従って適宜設定される。また、当該向上剤は、上記錠剤の製造方法に従い打錠することにより製造される。 The daily intake of the tablet of the present invention can be appropriately changed according to the subject of intake. For example, the dose for one adult (body weight 60 kg) is usually 0.01% in terms of the total dry weight or the total amount of the extract powder of Chinese herbal medicine extract. About 12 g, preferably about 0.05 to 10 g, more preferably about 0.07 to 8 g. In addition, for example, when using Fufutsu Seisaku as a Chinese herbal medicine, the total dry weight or extract powder of the extract is usually about 0.1 to 10 g, preferably about 1.0 to 8 g, more preferably 1.5 to 6 g. Degree. In addition, the pharmaceutical composition of the present invention is usually used in the form of oral administration divided into 2 to 3 times a day. The dose time is not particularly limited, but is preferably before or between meals.
(8) Hardness improver, disintegration improver The tablet hardness improver of the present invention comprises at least one pantethine selected from pantethine, pantethine salt, pantothenic acid, pantothenic acid salt, pantethein and panthenol. To increase the hardness of tablets containing at least one Chinese herbal medicine selected from the group consisting of Fufutsu Seisaku, Daishiba-ku-Daiko-to, Ho-so-Hao-yu and Dai-saiko-to it can. Specific materials of panthetins and herbal medicines, their blending ratios, and the like are appropriately set according to the above description. Moreover, the said improvement agent is manufactured by tableting according to the manufacturing method of the said tablet.
　また、本発明の錠剤の崩壊性向上剤は、パンテチン、パンテチンの塩、パントテン酸、パントテン酸の塩、パンテテインおよびパンテノールから選択される少なくとも１種のパンテチン類を有効成分とするものであり、防風通聖散、大柴胡去大黄湯、防已黄耆湯および大柴胡湯からなる群より選択される少なくとも１種の漢方薬を含有する錠剤の崩壊時間を短縮することができる。パンテチン類および漢方薬の具体的な材料およびそれらの配合割合等は、前述の記載に従って適宜設定される。また、当該向上剤は、上記錠剤の製造方法に従い打錠することにより製造される。 The tablet disintegration improver of the present invention comprises pantethine, pantethine salt, pantothenic acid, pantothenic acid salt, pantethein and panthenol as an active ingredient. The disintegration time of the tablet containing at least one Chinese herbal medicine selected from the group consisting of Fukatsutsu Seisaku, Daisaikoku Daihoto, Hosaihokanto and Daisaikoto can be shortened. Specific materials of panthetins and herbal medicines, their blending ratios, and the like are appropriately set according to the above description. Moreover, the said improvement agent is manufactured by tableting according to the manufacturing method of the said tablet.
　また、本発明の錠剤の硬度及び崩壊性向上剤は、パンテチン、パンテチンの塩、パントテン酸、パントテン酸の塩、パンテテインおよびパンテノールから選択される少なくとも１種のパンテチン類を有効成分とするものであり、防風通聖散、大柴胡去大黄湯、防已黄耆湯および大柴胡湯からなる群より選択される少なくとも１種の漢方薬を含有する錠剤の硬度を高めることができ、かつ崩壊時間を短縮することができる。パンテチン類および漢方薬の具体的な材料およびそれらの配合割合等は、前述の記載に従って適宜設定される。また、当該向上剤は、上記錠剤の製造方法に従い打錠することにより製造される。
（９）硬度向上方法、崩壊性向上方法
　本発明の錠剤の硬度向上方法によれば、防風通聖散、大柴胡去大黄湯、防已黄耆湯および大柴胡湯からなる群より選択される少なくとも１種の漢方薬と、パンテチン、パンテチンの塩、パントテン酸、パントテン酸の塩、パンテテインおよびパンテノールから選択される少なくとも１種のパンテチン類とを併用することにより、上記漢方薬を含有する錠剤の硬度を高めることができる。パンテチン類および漢方薬の具体的な材料およびそれらの配合割合等は、前述の記載に従って適宜設定される。また、当該向上剤は、上記錠剤の製造方法に従い打錠することにより製造される。 The tablet hardness and disintegration improver of the present invention comprises at least one panthetin selected from pantethine, pantethine salt, pantothenic acid, pantothenic acid salt, pantethein and panthenol as an active ingredient. Yes, it can increase the hardness of tablets containing at least one Chinese herbal medicine selected from the group consisting of Fufutsu Seisaku, Daisaikoku Daihoyu, Hosaihoyuto, and Daisaikoto. It can be shortened. Specific materials of panthetins and herbal medicines, their blending ratios, and the like are appropriately set according to the above description. Moreover, the said improvement agent is manufactured by tableting according to the manufacturing method of the said tablet.
(9) Hardness improvement method, disintegration improvement method According to the hardness improvement method of the tablet of the present invention, it is selected from the group consisting of Fufutsu Seisaku, Daisaikoku Daioyu, Hosaikouyuto, and Daisaikoto. Hardness of a tablet containing the above-mentioned Chinese medicine by using at least one kind of Chinese medicine and at least one kind of pantethine selected from pantethine, pantethine salt, pantothenic acid, pantothenic acid salt, pantethein and panthenol Can be increased. Specific materials of panthetins and herbal medicines, their blending ratios, and the like are appropriately set according to the above description. Moreover, the said improvement agent is manufactured by tableting according to the manufacturing method of the said tablet.
　本発明の錠剤の崩壊性向上方法によれば、防風通聖散、大柴胡去大黄湯、防已黄耆湯および大柴胡湯からなる群より選択される少なくとも１種の漢方薬と、パンテチン、パンテチンの塩、パントテン酸、パントテン酸の塩、パンテテインおよびパンテノールから選択される少なくとも１種のパンテチン類とを併用することにより、上記漢方薬を含有する錠剤の崩壊時間を短縮することができる。パンテチン類および漢方薬の具体的な材料およびそれらの配合割合等は、前述の記載に従って適宜設定される。また、当該向上剤は、上記錠剤の製造方法に従い打錠することにより製造される。 According to the method for improving disintegration of a tablet of the present invention, at least one herbal medicine selected from the group consisting of Fufutsu Seisaku, Daisaikoku Daihoto, Hosaihoyuto, and Daisaikoto, pantethine, pantethine By using together with at least one kind of pantethine selected from the salt of the above, pantothenic acid, salt of pantothenic acid, pantethein and panthenol, the disintegration time of the tablet containing the above Chinese medicine can be shortened. Specific materials of panthetins and herbal medicines, their blending ratios, and the like are appropriately set according to the above description. Moreover, the said improvement agent is manufactured by tableting according to the manufacturing method of the said tablet.
　本発明の錠剤の硬度および崩壊性向上方法によれば、防風通聖散、大柴胡去大黄湯、防已黄耆湯および大柴胡湯からなる群より選択される少なくとも１種の漢方薬と、パンテチン、パンテチンの塩、パントテン酸、パントテン酸の塩、パンテテインおよびパンテノールから選択される少なくとも１種のパンテチン類とを併用することにより、上記漢方薬を含有する錠剤の硬度を高めることができ、かつ崩壊時間を短縮することができる。パンテチン類および漢方薬の具体的な材料およびそれらの配合割合等は、前述の記載に従って適宜設定される。また、当該向上剤は、上記錠剤の製造方法に従い打錠することにより製造される。 According to the method for improving hardness and disintegration of a tablet of the present invention, at least one herbal medicine selected from the group consisting of Fufutsu Seisaku, Daisaikoku Daihoto, Hosai Koreito, and Daisaikoto, and pantethine , Panthetin salt, pantothenic acid, pantothenic acid salt, pantethein and at least one panthetin selected from panthenol can be used together to increase the hardness of the above-mentioned Chinese medicine-containing tablets and disintegrate Time can be shortened. Specific materials of panthetins and herbal medicines, their blending ratios, and the like are appropriately set according to the above description. Moreover, the said improvement agent is manufactured by tableting according to the manufacturing method of the said tablet.
　本発明によれば、パンテチン類に代えてマルチトール、マンニトールまたはソルビトールなどの従来結合剤として使用されている物質を漢方薬と併用した場合より、優れた硬度を錠剤に付与することができる。また、本発明によれば、漢方薬を含有する錠剤、さらには漢方薬以外の物質を含有する錠剤においても、硬度および／または崩壊時間を短縮させることができる。 According to the present invention, it is possible to impart superior hardness to tablets compared to the case where a substance conventionally used as a binder such as maltitol, mannitol or sorbitol is used in combination with Chinese medicine instead of pantetins. Further, according to the present invention, hardness and / or disintegration time can be shortened even in tablets containing Chinese herbal medicine, and in tablets containing substances other than Chinese herbal medicine.
　以下に実施例、処方例等を示して本発明をより詳細に説明するが、本発明はこれらに限定されない。
実施例１
　下記表２の配合割合にて、防風通聖散とパンテチンを混合した。 Hereinafter, the present invention will be described in more detail with reference to examples and formulation examples, but the present invention is not limited thereto.
Example 1
Fengtsu Seiseki and pantethine were mixed at the blending ratio shown in Table 2 below.
　防風通聖散としては、原料乾燥重量に換算して、トウキ１．２（重量部、以下同じ）、シャクヤク１．２、センキュウ１．２、サンシシ１．２、レンギョウ１．２、ハッカ１．２、ショウキョウ１．２、ケイガイ１．２、ボウフウ１．２、マオウ１．２、ダイオウ１．５、ボウショウ１．５、ビャクジュツ２．０、キキョウ２．０、オウゴン２．０、カンゾウ２．０、セッコウ２．０およびカッセキ３．０を、水２０倍量を用いて約１００℃で１時間抽出し、遠心分離して抽出液を得、減圧下で濃縮してスプレードライを用いて乾燥した「防風通聖散エキス末」（スプレードライヤーによる乾燥は、抽出液を回転数１００００ｒｐｍのアトマイザーに落下させ、１５０℃の空気の熱風を供給して行った）を用いた。また、パンテチン類としては、８０重量％パンテチン水溶液である「パンテチンＡ」（第一ファインケミカル株式会社製）を用いた。表中の配合割合は、防風通聖散エキス末については乾燥重量、パンテチンについては、パンテチンＡのパンテチン含有率（８０重量％）からそれぞれ算出した値である。得られた混合物０．３６ｇを油圧打錠機ＳＭＰ－３（理研精機株式会社製）を用いて圧力２５Ｍｐａにて直径９ｍｍの凸型錠剤を打錠して錠剤を得た。この打錠時に杵や臼への錠剤の付着の有無を確認した。 As windproof tsusan san, in terms of raw material dry weight, Toki 1.2 (parts by weight, the same shall apply hereinafter), Peonies 1.2, Senkyu 1.2, Sanshi 1.2, Forsythia 1.2, Hakka 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-Ju 2.0, Ogon 2.0, Licorice 2 0.0, gypsum 2.0 and Kasseki 3.0 were extracted with about 20 times the amount of water at about 100 ° C. for 1 hour, centrifuged to obtain an extract, concentrated under reduced pressure, and spray dried. The dried “Fengshutsu Seisaku Extract Powder” (drying with a spray dryer was performed by dropping the extract into an atomizer with a rotational speed of 10000 rpm and supplying hot air at 150 ° C.). Moreover, as pantetins, “pantethine A” (manufactured by Daiichi Fine Chemical Co., Ltd.), which is an 80 wt% pantethine aqueous solution, was used. The blending ratios in the table are the values calculated from the dry weight for Fengtsutsu Seisaku Extract powder and the pantethine content (80% by weight) of pantethine A for pantethine, respectively. Using 0.36 g of the obtained mixture, a convex tablet having a diameter of 9 mm was tableted using a hydraulic tableting machine SMP-3 (manufactured by Riken Seiki Co., Ltd.) at a pressure of 25 Mpa to obtain a tablet. At the time of tableting, it was confirmed whether or not the tablets adhered to the punch or mortar.
　得られた錠剤について、木屋式デジタル硬度計ＫＨＴ－２０Ｎ型（株式会社藤原製作所製）を用いて、錠剤に対して垂直方向の硬度を測定した。垂直方向は、打錠時に杵で加圧・圧縮する方向であり、水平方向は、垂直方向に対して直角の方向である。 The obtained tablets were measured for hardness in the direction perpendicular to the tablets using a Kiya type digital hardness tester KHT-20N (manufactured by Fujiwara Seisakusho Co., Ltd.). The vertical direction is the direction of pressing and compressing with a scissors during tableting, and the horizontal direction is the direction perpendicular to the vertical direction.
　また、得られた錠剤について崩壊時間を測定し、崩壊性の評価を防風通聖散単独からなる錠剤と比較して行った。各処方１０錠の平均値の結果を表２に記した。
（崩壊時間の測定）
　１００ｍｌビーカーに３７℃の水８０ｍｌをいれ、２ｃｍのスターラーバーを４００ｒｐｍにて回転させ、錠剤を投入してから錠剤が目視により観察できなくなるまでの時間を測定した。 Moreover, disintegration time was measured about the obtained tablet, and disintegration evaluation was performed compared with the tablet which consists of a wind-proof tsuyosan alone. The results of the average value of each tablet of 10 tablets are shown in Table 2.
(Measurement of disintegration time)
A 100 ml beaker was charged with 80 ml of water at 37 ° C., a 2 cm stirrer bar was rotated at 400 rpm, and the time from when the tablet was introduced until the tablet could no longer be observed visually was measured.
　（崩壊性の評価）
　防風通聖散単独からなる錠剤の崩壊時間（Ｔ０）に対する、防風通聖散およびパンテチン類からなる錠剤の崩壊時間（Ｔｘ）の割合の逆数、すなわち（Ｔ０／Ｔｘ）を算出して評価した。 (Evaluation of disintegration)
Calculate the reciprocal of the ratio of the disintegration time (T x ) of Fengtsu Sanseiki and the panthetins to the disintegration time (T 0 ) of the tablet consisting of Fengtsu Sanjo alone, ie, (T 0 / T x ) And evaluated.
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
　表２から明らかなように、防風通聖散エキス末にパンテチンを加えることにより、硬度の増加と、パンテチン類の添加濃度依存的な崩壊時間の短縮が観られた。防風通聖散１００重量部に対するパンテチン類の総量が０．１重量部である場合、パンテチン類を含有しない錠剤と比較して、錠剤強度は格段に向上した。さらに、防風通聖散１００重量部に対するパンテチン類の総量が１．０重量部である場合には、前者よりさらに錠剤強度が向上した。一方、防風通聖散１００重量部に対するパンテチン類の総量が３０重量部である場合には、打錠時に杵や臼への錠剤の付着が確認された。
実施例２
　前記実施例１において、パンテチン類としてパンテチンを用い、パンテチンとしては「パントシン（登録商標）散５０％」（第一三共株式会社製）を使用した。下記表３の配合割合で混合した以外は、上記実施例１と同様にして錠剤を製造し、硬度および崩壊時間を測定し、打錠時の杵や臼への付着の有無を観察した。なお、パンテチンの配合割合は細粒中のパンテチン含有率（５０重量％）に基づき算出した。各処方１０錠の平均値の結果を表３に記した。 As is apparent from Table 2, by adding pantethine to the windproof tsushosan extract powder, an increase in hardness and a shortening of the disintegration time depending on the addition concentration of panthetins were observed. When the total amount of panthetins relative to 100 parts by weight of Fengtsu Sansho was 0.1 parts by weight, the tablet strength was remarkably improved as compared with tablets containing no pantetins. Furthermore, when the total amount of panthetines relative to 100 parts by weight of Fengtsu Sansho was 1.0 part by weight, the tablet strength was further improved from the former. On the other hand, when the total amount of panthetins was 100 parts by weight relative to 100 parts by weight of Fukatsu Tsushosan, it was confirmed that the tablets adhered to the punches and mortars during tableting.
Example 2
In Example 1, pantethine was used as the pantethine, and “pantocin (registered trademark) powder 50%” (Daiichi Sankyo Co., Ltd.) was used as the pantethine. Except for mixing at the blending ratios shown in Table 3 below, tablets were produced in the same manner as in Example 1 above, the hardness and disintegration time were measured, and the presence or absence of adhesion to the wrinkles and dies during tableting was observed. In addition, the compounding ratio of pantethine was calculated based on the pantethine content (50% by weight) in the fine granules. The results of the average value of 10 tablets for each formulation are shown in Table 3.
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000003
　表３から明らかなように、上記パンテチンの細粒を使用した場合も、前記実施例１と同様に硬度の増加と、パンテチン類の添加濃度依存的な崩壊時間の短縮が観られた。防風通聖散１００重量部に対するパンテチン類の総量が０．１重量部である場合、パンテチン類を含有しない錠剤と比較して、錠剤強度は格段に向上した。さらに、防風通聖散１００重量部に対するパンテチン類の総量が１．０重量部である場合には、前者よりさらに錠剤強度が向上した。一方、防風通聖散１００重量部に対するパンテチン類の総量が３０重量部である場合には、打錠時に杵や臼への錠剤の付着が確認された。
実施例３
　実施例１において、防風通聖散エキス末に代えて大柴胡湯を用いた以外は、実施例１と同様に錠剤を得た。その結果、硬度については、防風通聖散エキス末を用いた実施例１の結果より劣るものの、硬度および崩壊時間について、それぞれ実施例１と同様の傾向がみられた。また、大柴胡去大黄湯または防已黄耆湯を用いた以外は、実施例１と同様に錠剤を得た。結果としては、硬度および崩壊時間について、それぞれ実施例１と同様の傾向がみられたが、硬度については、防風通聖散エキス末を用いた実施例１の方がより高かった。 As is apparent from Table 3, even when the pantethine fine granules were used, an increase in hardness and a reduction in the disintegration time depending on the addition concentration of panthetins were observed as in Example 1. When the total amount of panthetins relative to 100 parts by weight of Fengtsu Sansho was 0.1 parts by weight, the tablet strength was remarkably improved as compared with tablets containing no pantetins. Furthermore, when the total amount of panthetines relative to 100 parts by weight of Fengtsu Sansho was 1.0 part by weight, the tablet strength was further improved from the former. On the other hand, when the total amount of panthetins was 100 parts by weight relative to 100 parts by weight of Fukatsu Tsushosan, it was confirmed that the tablets adhered to the punches and mortars during tableting.
Example 3
In Example 1, tablets were obtained in the same manner as in Example 1 except that Daisaikoto was used in place of the Fufutsu Seisaku extract powder. As a result, although the hardness was inferior to the result of Example 1 using the Fufutsu Seisaku extract powder, the same tendency as in Example 1 was observed for the hardness and the disintegration time. In addition, tablets were obtained in the same manner as in Example 1 except that Daishiba Kodai Daio-to or Ho-Kai-San-to was used. As a result, the same tendency as in Example 1 was observed with respect to the hardness and the disintegration time, but the hardness was higher in Example 1 using Fufutsu Seisaku extract powder.
比較例１～３
　前記実施例１において、パンテチンに代えてマルチトール（東和化成工業株式会社製「レシス」：比較例１）、マンニトール（三栄源エフ・エフ・アイ株式会社製「マンニトール」：比較例２）またはソルビトール（ソルビトール（三栄源エフ・エフ・アイ株式会社製）：比較例３）を使用し、下記表４～６の配合割合で混合した以外は、上記実施例１と同様にして錠剤を製造し、硬度を測定した。マルチトール、マンニトールおよびソルビトールは通常結合剤として使用されるものである。各処方１０錠の平均値の結果を表４～６に記した。 Comparative Examples 1 to 3
In Example 1, instead of pantethine, maltitol (“Resis” manufactured by Towa Kasei Kogyo Co., Ltd .: Comparative Example 1), mannitol (“Mannitol” manufactured by Saneigen FFI Co., Ltd .: Comparative Example 2) or sorbitol (Sorbitol (manufactured by San-Ei Gen FFI Co., Ltd.): Comparative Example 3) was used to produce a tablet in the same manner as in Example 1 except that mixing was performed at the blending ratios shown in Tables 4 to 6 below. Hardness was measured. Maltitol, mannitol and sorbitol are usually used as binders. The results of the average value of 10 tablets for each formulation are shown in Tables 4-6.
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000005
Figure JPOXMLDOC01-appb-T000005
Figure JPOXMLDOC01-appb-T000006
Figure JPOXMLDOC01-appb-T000006
　表４～６から明らかなように、結合剤として一般的に使用されるマルチトール、マンニトールまたはソルビトールを加えた場合は、望まれるほどの硬度の増加は観られなかった。
処方例１～３６
　処方例１～３６に従い、常法により錠剤を製した。 As is apparent from Tables 4-6, the desired increase in hardness was not observed when maltitol, mannitol or sorbitol, commonly used as binders, were added.
Formulation Examples 1-36
According to Formulation Examples 1 to 36, tablets were produced by a conventional method.
Figure JPOXMLDOC01-appb-T000007
Figure JPOXMLDOC01-appb-T000007
Figure JPOXMLDOC01-appb-T000008
Figure JPOXMLDOC01-appb-T000008
Figure JPOXMLDOC01-appb-T000009
Figure JPOXMLDOC01-appb-T000009
Figure JPOXMLDOC01-appb-T000010
Figure JPOXMLDOC01-appb-T000010
Figure JPOXMLDOC01-appb-T000011
Figure JPOXMLDOC01-appb-T000011
Figure JPOXMLDOC01-appb-T000012
Figure JPOXMLDOC01-appb-T000012

Claims (4)

  1. 防風通聖散、大柴胡去大黄湯、防已黄耆湯および大柴胡湯からなる群より選択される少なくとも１種の漢方薬、ならびにパンテチン、パンテチンの塩、パントテン酸、パントテン酸の塩、パンテテインおよびパンテノールから選択される少なくとも１種のパンテチン類を含有する錠剤。 At least one Chinese herbal medicine selected from the group consisting of Fenghuang Seongsan, Daisaikou Daiho-to, Hosaiho-to and Dai-saiko-to, and pantethine, pantethine salt, pantothenic acid, pantothenic acid salt, pantethein and A tablet containing at least one panthetin selected from panthenol.
  2. 錠剤の垂直方向の硬度が６Ｎ以上である、請求項１に記載の錠剤。 The tablet according to claim 1, wherein the tablet has a vertical hardness of 6N or more.
  3. パンテチン、パンテチンの塩、パントテン酸、パントテン酸の塩、パンテテインおよびパンテノールから選択される少なくとも１種のパンテチン類を有効成分とする、防風通聖散、大柴胡去大黄湯、防已黄耆湯および大柴胡湯からなる群より選択される少なくとも１種の漢方薬を含有する錠剤の硬度及び崩壊性向上剤。 Pantsuchin, Pantethine salt, Pantothenic acid, Pantothenic acid salt, Pantethein and Panthenol selected from Pantethine and Panthetin as active ingredients And a tablet hardness and disintegration improver containing at least one Chinese herb selected from the group consisting of Daisaikoto.
  4. 防風通聖散、大柴胡去大黄湯、防已黄耆湯および大柴胡湯からなる群より選択される少なくとも１種の漢方薬と、パンテチン、パンテチンの塩、パントテン酸、パントテン酸の塩、パンテテインおよびパンテノールから選択される少なくとも１種のパンテチン類とを併用する、上記漢方薬を含有する錠剤の硬度及び崩壊性向上方法。 At least one herbal medicine selected from the group consisting of Fufutsu Seisaku, Daisaikou Daihoyu, Hosaihoyuto and Daishibayu, and pantethine, pantethine salt, pantothenic acid, pantothenic acid salt, pantethein and A method for improving hardness and disintegration of a tablet containing the above-mentioned Chinese medicine, which is used in combination with at least one pantetin selected from panthenol.
PCT/JP2009/051228 2008-01-25 2009-01-26 Tablet comprising kanpo herbal medicine and pantethine component WO2009093736A1 (en)

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CN102688336A (en) * 2012-03-16 2012-09-26 江西天施康中药股份有限公司 Bezoar supernatant composite and preparation method thereof
JP2018058830A (en) * 2016-09-28 2018-04-12 小林製薬株式会社 tablet

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