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WO2002051384A1 - Procede pour stabiliser une suspension et suspension stabilisee - Google Patents

Procede pour stabiliser une suspension et suspension stabilisee Download PDF

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Publication number
WO2002051384A1
WO2002051384A1 PCT/JP2001/011271 JP0111271W WO02051384A1 WO 2002051384 A1 WO2002051384 A1 WO 2002051384A1 JP 0111271 W JP0111271 W JP 0111271W WO 02051384 A1 WO02051384 A1 WO 02051384A1
Authority
WO
WIPO (PCT)
Prior art keywords
starch
fatty acid
suspension
polyoxyethylene
nonionic surfactant
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2001/011271
Other languages
English (en)
Japanese (ja)
Inventor
Susumu Abe
Tomonori Isoda
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Chugai Pharmaceutical Co Ltd
Original Assignee
Chugai Pharmaceutical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Chugai Pharmaceutical Co Ltd filed Critical Chugai Pharmaceutical Co Ltd
Priority to JP2002552530A priority Critical patent/JP4204864B2/ja
Publication of WO2002051384A1 publication Critical patent/WO2002051384A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • 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
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • 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
    • A61P1/12—Antidiarrhoeals
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K23/00—Use of substances as emulsifying, wetting, dispersing, or foam-producing agents
    • C09K23/017—Mixtures of compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin

Definitions

  • the present invention provides a stock suspension comprising starch or a starch derivative and a nonionic surfactant, and an aqueous suspension comprising mixing a water-insoluble solid component with the suspension.
  • the present invention relates to a method for stabilizing an aqueous suspension of a water-insoluble solid component, which further comprises using a starch, or a starch derivative, and a nonionic surfactant in combination.
  • the suspension of the present invention is particularly suitable for stably suspending a crude drug, an antacid, an antidiarrheal, etc., which are water-insoluble solid substances.
  • tablets, capsules, granules, fine granules, powders, etc., of pharmaceuticals containing crude drug components, antacids or antidiarrheals, or foods containing crude drug components are water-insoluble solid substances. Many of them are used as solid preparations.
  • solid preparations have the disadvantage that it takes a long time to disintegrate, and it takes a long time for the medicinal effect to develop after taking the drug.
  • the dosage form is liquid, there is no such a problem as described above, and the feeling of drinking is excellent and can be easily taken. For this reason, suspensions containing crude drug components, antacids or antidiarrheals have recently been provided.
  • a suspension suitable for incorporating a water-insoluble solid component such as a crude drug component, an antacid or an antidiarrheal wherein the solid component in the suspension does not settle out for a long time and has a suspension stability and There has been a demand for a technique capable of easily and inexpensively providing a suspension having excellent redispersibility.
  • the present inventors have conducted intensive studies to obtain a suspension having good suspension stability and redispersibility.As a result, surprisingly, starch or a starch derivative and a nonionic surfactant By combining these, it can be manufactured by the conventional method because it is a liquid with low viscosity at the time of manufacture, and the suspension does not change to a gel state during standing and storage to cause aggregation or precipitation of suspended solid component particles. It was found that a suspension was obtained. This suspension has the characteristic that it becomes a liquid with low viscosity by shaking at the time of drinking and is easy to drink.
  • the suspension obtained by removing the water-insoluble solid component from the suspension that is, a suspension stock solution in which starch or a starch derivative is combined with a nonionic surfactant, or a suspension stock solution consisting of starch or a starch derivative alone
  • a suspension stock solution in which starch or a starch derivative is combined with a nonionic surfactant or a suspension stock solution consisting of starch or a starch derivative alone
  • the present invention by blending starch or a starch derivative as a suspending agent in a suspension and adding a nonionic surfactant to the suspension, agglomeration or sedimentation of particles occurs even during long-term storage. Without forming a lump that does not disperse when shaken (cake The present invention provides a suspension that can be prevented from being caused.
  • the pharmaceutical containing a crude drug can be prepared by mix
  • the present invention can be used for pharmaceuticals containing other water-insoluble solid components, foods, detergents, paints, etc. in addition to the above-mentioned crude drug-containing pharmaceuticals, but is not limited to these fields. is not.
  • the starch that can be used in the present invention is not particularly limited, and examples thereof include corn starch, waxy corn starch, potato starch, tapio starch, wheat starch and the like.
  • examples of the starch derivatives that can be used in the present invention include, for example, hydroxyethyl starch, hydroxypropyl starch and the like as etherified starch, and starch acetate and phosphate phosphate as esterified starch.
  • examples of the starch include formaldehyde crosslinked starch, phosphoric acid crosslinked starch, and the like, acid-treated starch, oxidized starch, and alpha-unified starch. And the like. However, it is not limited to these.
  • the amount of the starch and / or starch derivative is such that it can form a gel when dissolved or cooled in water or hot water, and can achieve the appropriate viscosity required for the use of the suspension. Any concentration is acceptable.
  • starch or starch derivatives can be used in the range of 0.5 to 10% by weight, preferably 1.0 to 5.0% by weight, based on the weight of an aqueous medium such as water.
  • the nonionic surfactant which can be used in the present invention is not particularly limited. Oxypropylene alkyl ether, polyhydric alcohol fatty acid partial ester, polyoxyethylene fatty acid ester, triethanol Lumamine fatty acid ester, polyoxetylene polystyrylphenyl ether, fatty acid diethanolamide, etc. Preferred are polyhydric alcohol fatty acid partial esters such as esters and polydaricerin fatty acid esters.
  • the amount of the nonionic surfactant of the present invention is such that it can be used together with starch or a starch derivative to give a stable suspension and does not inhibit the efficacy of the pharmaceutical ingredient.
  • any concentration may be used as long as the appropriate viscosity required for the use of the suspension can be achieved.
  • 0.01 to 1.0% by weight, preferably 0.01 to 0.5% by weight, based on the weight of the aqueous medium, is incorporated.
  • the nonionic surfactant is dissolved in water or the like in advance, and then starch or a starch derivative is added thereto and dissolved by stirring and heating.
  • starch or a starch derivative is added to water and stirred and dissolved by heating, and then the nonionic surfactant is blended as it is or in a state of being dissolved in water in advance and stirred and dissolved.
  • the starch or starch derivative may be used by first suspending it in water, and then adding this suspension to previously heated water followed by stirring and dissolving.
  • water-insoluble solid component used in the present invention examples include, but are not limited to, crude drugs, antacids, and antidiarrheals.
  • the crude drug component in the crude drug component-containing suspension is not particularly limited, as long as it is insoluble in water.
  • the antacid in the suspension containing the antacid is dried aluminum hydroxide gel, magnesium calcium aluminate, magnesium bismuth aluminate magnesium, magnesium calcium silicate, natural aluminum silicate, synthetic aluminum gateate, synthetic Hydrotalcite, magnesium oxide, magnesium aluminate hydroxide, aluminum hydroxide gel, co-precipitated product of aluminum hydroxide and sodium bicarbonate, mixed dry gel of aluminum hydroxide and magnesium carbonate, aluminum hydroxide and magnesium carbonate-calcium carbonate Precipitated product, magnesium hydroxide, magnesium carbonate, precipitated calcium carbonate, magnesium metasilicate aluminate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, sword bone, Ishige, Borei, sucrose sulfate aluminum Salts and the like.
  • the antidiarrheal in the antidiarrheal-containing suspension includes kaolin, natural aluminum gayate, aluminum hydroxynaphthoate, pectin, medicinal charcoal, precipitated calcium carbonate, calcium lactate, calcium hydrogen phosphate, aesyaku powder, pie powder, Examples include the end of opaque, the end of oren, the end of kujin, the end of genoshoko, the end of quince, the end of hawthorn, the end of sempuri, and the end of lobich.
  • the compounding amount of the water-insoluble solid component of the present invention in the suspension is any amount as long as it is an amount sufficient to exhibit the intended medicinal effect and an amount that can maintain a stable suspension state. Is also good. Usually, it is at most 50% by weight, preferably at most 20% by weight, based on the total amount of the suspension.
  • the suspension of the present invention can typically be prepared as follows. First, the above starch Alternatively, a predetermined amount of the starch derivative is added to an aqueous medium at 60 to 90 ° C, usually water (hot water), and dissolved by stirring to form a uniform gel. Alternatively, the starch or starch derivative is dispersed in cold water and heated with stirring to form a uniform gel. Here, a predetermined amount of a nonionic surfactant is blended. On the other hand, the solid component is separately dispersed in water, and this dispersion is added to a previously prepared mixture of starch or a starch derivative and a nonionic surfactant, followed by mixing to obtain the desired aqueous suspension. Obtainable. The solid components can be directly mixed without being dispersed, but mixing as a dispersed liquid is easier to process and has better suspension efficiency.
  • the suspension of the present invention thus obtained shows good suspension stability and redispersibility, and its viscosity change rate is preferably 10% or more.
  • the viscosity change rate refers to the viscosity of the suspension at rest (viscosity before shaking) and the viscosity of the suspension when shaken (viscosity after shaking), respectively. This is an index indicating the change in viscosity before and after shaking.
  • the viscosity change rate (%) can be expressed by the following equation.
  • Viscosity change rate (%)
  • standing means to leave for 1 hour or more without shaking.
  • the suspension of the present invention is a liquid having a low viscosity at the time of production, it can be prepared by a conventional method.
  • the suspension particles which are solid components in a gel state having a high viscosity, aggregate or precipitate. Can be prevented. Also, when drinking, shaking lowers the viscosity, making drinking easier.
  • the above hydroxypropyl starch was dispersed in predetermined water, and the mixture was stirred while heating to 90 ° C. to gel.
  • the sucrose fatty acid ester was dissolved in a small amount of water, and this solution was added to the above gelling solution and mixed.
  • An antacid dispersion prepared by dispersing separately prepared magnesium aluminate metasilicate, aluminum sulfate sucrose sulfate and synthetic hydrotalcite in water was added to the blended liquid thus obtained and mixed.
  • the desired antacid-containing suspension was obtained.
  • the concentration of sucrose fatty acid ester was set to 0%, and the antacid mixture was prepared in the same manner as above. A suspension was prepared. The antacid-containing suspension thus obtained was stored in a constant temperature bath at 50 ° C for 4 weeks, and then the appearance and viscosity were evaluated. The results are shown in Table 1 below.
  • the suspension containing the starch derivative and the nonionic surfactant prevents the suspended particles from agglomeration and sedimentation in a gel state during standing storage, and shakes during drinking. As a result, the suspension was quickly redispersed into a low-viscosity liquid, which was easily drinkable.
  • the suspension containing the starch derivative and the nonionic surfactant was transformed into a stable gel state by shaking once and then allowed to stand.
  • the suspension had the reversible property of becoming a low viscosity liquid.
  • Vitamin B 2 0 1 1%
  • Nonionic surfactant 0 1%
  • a crude drug-containing suspension was prepared in the same manner as in Example 1.
  • 0.75% of gelatin or sodium alginate was used as a suspending agent instead of a combination of a nonionic surfactant and a starch derivative. 1.0% was prepared as a crude drug-containing suspension in the same manner as above.
  • the suspension containing the starch derivative and the nonionic surfactant has a lower viscosity than the suspension containing the suspending agent of the comparative example, but remains in a gel state during standing.
  • the suspension prevented aggregation and precipitation of suspended particles, and was rapidly redispersed by shaking when drinking.
  • the crude drug-containing suspension containing the starch derivative and the nonionic surfactant contains almost the same amount of crude drug as the crude drug-containing solution in the comparative example, A highly scented and effective preparation can be obtained.
  • the suspension prevents aggregation and precipitation of the suspended particles, and is a suspension that is rapidly redispersed by shaking when drinking, and has an excellent drinking sensation.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Materials Engineering (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne une suspension obtenue en incorporant à une suspension un amidon ou un dérivé d'amidon servant d'agent de dispersion et en y ajoutant un agent tensio-actif non ionique. Cette suspension ne fait pas l'objet d'agrégation ou de sédimentation de particules solides, même en cas de stockage à long terme, et est parfaitement adaptée à une remise en suspension. Il est possible d'introduire un ingrédient solide non soluble dans l'eau, tel qu'un ingrédient à base d'herbes médicinales, un agent antiacide ou un agent antidiarrhéique, dans la suspension selon cette invention. Cette suspension présente une très bonne stabilité en suspension et est parfaitement adaptée à une remise en suspension, de façon que des ingrédients solides contenus dans cette suspension ne se déposent pas pour longtemps. En outre, la préparation de la suspension selon cette invention est aisée et bon marché.
PCT/JP2001/011271 2000-12-25 2001-12-21 Procede pour stabiliser une suspension et suspension stabilisee Ceased WO2002051384A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2002552530A JP4204864B2 (ja) 2000-12-25 2001-12-21 懸濁液の安定化方法及び安定化された懸濁液

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2000-391987 2000-12-25
JP2000391987 2000-12-25

Publications (1)

Publication Number Publication Date
WO2002051384A1 true WO2002051384A1 (fr) 2002-07-04

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Application Number Title Priority Date Filing Date
PCT/JP2001/011271 Ceased WO2002051384A1 (fr) 2000-12-25 2001-12-21 Procede pour stabiliser une suspension et suspension stabilisee

Country Status (2)

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JP (1) JP4204864B2 (fr)
WO (1) WO2002051384A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20160049960A (ko) 2014-10-28 2016-05-10 라이온 가부시키가이샤 액상 조성물

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS63258820A (ja) * 1987-04-17 1988-10-26 Sato Seiyaku Kk 止瀉剤含有内用懸濁剤
EP0405930A2 (fr) * 1989-06-28 1991-01-02 McNEIL-PPC, INC. Suspension pharmaceutique aqueuse pour des agents actifs pharmaceutiques essentiellement insolubles dans l'eau
JPH059125A (ja) * 1991-06-28 1993-01-19 Nippon Saafuakutanto Kogyo Kk ローヤルゼリーの水分散液
EP0560329A1 (fr) * 1992-03-10 1993-09-15 Ss Pharmaceutical Co., Ltd. Composition pharmaceutique ayant des propriétés de mise en suspension contenant du pranoprofène
JPH09278661A (ja) * 1996-04-05 1997-10-28 Fuji Chem Ind Co Ltd 懸濁液剤
JPH10287565A (ja) * 1997-04-11 1998-10-27 Taiyo Yakuhin Kogyo Kk プラノプロフェン懸濁シロップ剤

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5624478A (en) * 1979-08-06 1981-03-09 Nippon Saafuakutanto Kogyo Kk Thickening and gelatinizing agent
JPH0696536B2 (ja) * 1988-02-26 1994-11-30 佐藤製薬株式会社 制酸剤含有内用懸濁液
JP2855057B2 (ja) * 1993-07-09 1999-02-10 株式会社資生堂 増粘ゲル化剤及び増粘ゲル状組成物
JP3927253B2 (ja) * 1995-02-02 2007-06-06 中外製薬株式会社 スクラルファート製剤
JP3117647B2 (ja) * 1996-10-18 2000-12-18 株式会社資生堂 口紅組成物

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS63258820A (ja) * 1987-04-17 1988-10-26 Sato Seiyaku Kk 止瀉剤含有内用懸濁剤
EP0405930A2 (fr) * 1989-06-28 1991-01-02 McNEIL-PPC, INC. Suspension pharmaceutique aqueuse pour des agents actifs pharmaceutiques essentiellement insolubles dans l'eau
JPH059125A (ja) * 1991-06-28 1993-01-19 Nippon Saafuakutanto Kogyo Kk ローヤルゼリーの水分散液
EP0560329A1 (fr) * 1992-03-10 1993-09-15 Ss Pharmaceutical Co., Ltd. Composition pharmaceutique ayant des propriétés de mise en suspension contenant du pranoprofène
JPH09278661A (ja) * 1996-04-05 1997-10-28 Fuji Chem Ind Co Ltd 懸濁液剤
JPH10287565A (ja) * 1997-04-11 1998-10-27 Taiyo Yakuhin Kogyo Kk プラノプロフェン懸濁シロップ剤

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20160049960A (ko) 2014-10-28 2016-05-10 라이온 가부시키가이샤 액상 조성물

Also Published As

Publication number Publication date
JP4204864B2 (ja) 2009-01-07
JPWO2002051384A1 (ja) 2004-04-22

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