WO2014050851A1 - Oral liquid composition - Google Patents

Oral liquid composition Download PDF

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Publication number
WO2014050851A1
WO2014050851A1 PCT/JP2013/075823 JP2013075823W WO2014050851A1 WO 2014050851 A1 WO2014050851 A1 WO 2014050851A1 JP 2013075823 W JP2013075823 W JP 2013075823W WO 2014050851 A1 WO2014050851 A1 WO 2014050851A1
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Prior art keywords
liquid composition
polyoxyethylene
examples
mol
internal liquid
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PCT/JP2013/075823
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French (fr)
Japanese (ja)
Inventor
恵美 石田
亨 中村
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大正製薬株式会社
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Priority to JP2014538511A priority Critical patent/JP6260538B2/en
Publication of WO2014050851A1 publication Critical patent/WO2014050851A1/en

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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
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/52—Adding ingredients
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15—Vitamins
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • 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
    • A61P3/02—Nutrients, e.g. vitamins, minerals

Definitions

  • the present invention relates to a liquid composition for internal use in which a poorly water-soluble vitamin, an oil component, or a herbal extract is stably dissolved in a liquid composition for a long period of time.
  • Solubilizing agents are required when blending sparingly water-soluble ingredients such as sparingly water-soluble vitamins and oil ingredients and herbal extracts into beverages such as drinks at low pH.
  • a solubilizer is required for the poorly water-soluble component, but also in a crude drug extract, a solubilizer is necessary because it causes turbidity and precipitation in the long term due to hydrolysis.
  • low pH is suitable for drinks, such as a drink agent, from viewpoints, such as antiseptic
  • Patent Document 1 Japanese Patent Document 1
  • an object of the present invention is to provide an internal liquid composition in which a poorly water-soluble vitamin, oil component, or herbal extract is stably dissolved for a long period of time without causing turbidity or precipitation even at a low pH. .
  • the present inventors used one or more selected from polyoxyethylene lauryl ether, polyoxyethylene phytosterol, and polyoxyethylene phytostanol as a solubilizer, It has been found that a poorly water-soluble vitamin, an oil component, or a herbal extract can be stably dissolved for a long period of time by blending polyhydric alcohols.
  • the aspect of the present invention completed based on such findings is as follows.
  • a transparent oral liquid composition that can dissolve a poorly water-soluble vitamin, an oil component, or a herbal extract stably for a long period of time.
  • the sparingly water-soluble vitamin used in the present invention refers to a sparingly water-soluble vitamin that can be taken internally, such as vitamin E, vitamin E derivatives such as vitamin E fatty acid esters (for example, tocopherol acetate), vitamin A, vitamin D, and vitamin K.
  • the oil component means a fat-soluble substance having a biological activity, a fragrance (synthetic fragrance or natural fragrance), or an essential oil that can be taken internally. Examples of the fat-soluble substance having a physiological activity include ⁇ -oryzanol and ⁇ -linolene.
  • fragrances synthetic fragrances / natural fragrances
  • essential oils include citral, limonene, etc. Or natural-derived fragrances or essential oils.
  • the poorly water-soluble vitamin and oil component may be blended alone or in combination of two or more. The blending amount of these in the internal liquid composition is not particularly limited, but is preferably 0.0001 to 1% by mass, more preferably 0.001 to 0.5% by mass, and most preferably 0.002 to 0.05%. % By mass.
  • Herbal extracts used in the present invention are extract powder, extract extract, flow extract, etc., but are not particularly limited as long as they can be taken orally, and herbal medicines include carrots, rouges, scallions, licorice, taisou, chimpi, sandalwood.
  • the polyoxyethylene lauryl ether used in the present invention has an addition mole number of oxyethylene of 5 to 50 moles, and the polyoxyethylene phytosterol and polyoxyethylene phytostanol have a polyoxyethylene addition mole number of 5 to 50 moles.
  • Ethylene phytosterol Specifically, polyoxyethylene (25 mol) lauryl ether, polyoxyethylene (5 mol) phytosterol, polyoxyethylene (10 mol) phytosterol, polyoxyethylene (20 mol) phytosterol, polyoxyethylene (30 mol) phytosterol , Polyoxyethylene (25 mol) phytostanol, and the like. These may be used alone or in combination of two or more.
  • the amount of one or more selected from polyoxyethylene lauryl ether, polyoxyethylene phytosterol, and polyoxyethylene phytostanol is not particularly limited, but one or more selected from poorly water-soluble vitamins, oil components, and herbal extracts
  • the amount is usually 0.02 to 500 parts by mass, preferably 0.05 to 200 parts by mass, and more preferably 0.5 to 100 parts by mass with respect to 1 part by mass. If the amount of polyoxyethylene lauryl ether, polyoxyethylene phytosterol, or polyoxyethylene phytostanol is too small, turbidity and precipitation may be generated, and a liquid composition with good commercial properties and stability may not be obtained.
  • polyhydric alcohol used in the present invention examples include one selected from ethylene glycol, propylene glycol, 1,3-butylene glycol, dipropylene glycol, isoprene glycol, polyethylene glycol, glycerin, polyglycerin, diglycerin, and sorbitol.
  • ethylene glycol propylene glycol
  • 1,3-butylene glycol dipropylene glycol
  • isoprene glycol polyethylene glycol
  • glycerin polyglycerin
  • diglycerin diglycerin
  • sorbitol sorbitol
  • the above is mentioned.
  • at least one selected from glycerin and sorbitol is preferable, and the blending amount of polyhydric alcohols is not particularly limited, but at least one selected from poorly water-soluble vitamins, oil components, and herbal extracts.
  • the amount is usually 0.02 to 500 parts by mass, preferably 0.05 to 200 parts by mass, and more preferably 1 to 100 parts by mass with respect to
  • the oral liquid composition of the present invention was in a transparent state even after long-term storage, and further maintained in a transparent state without precipitation even in a low-temperature environment after long-term storage.
  • the low temperature preferably means 10 ° C. or less, more preferably 5 ° C. or less.
  • the pH of the internal liquid composition of the present invention is preferably 2.0 to 4.0 from the viewpoint of flavor and antiseptic properties.
  • organic acids such as citric acid, malic acid, fumaric acid, tartaric acid, lactic acid and succinic acid, or salts of these organic acids, inorganic acids such as phosphoric acid and hydrochloric acid, inorganic acids such as sodium hydroxide, etc.
  • a base can be used.
  • the liquid composition for internal use of the present invention can be used as a liquid preparation for internal use in food fields such as nutritional functional food and food for specified insurance, in addition to pharmaceuticals and quasi drugs.
  • liquid composition for internal use of the present invention water-soluble vitamins, minerals, amino acids, royal jelly, caffeine and the like can be appropriately blended as long as the effects of the present invention are not impaired.
  • additives such as antioxidants, colorants, fragrances, flavoring agents, surfactants, solubilizers, preservatives, sweeteners, and the like are appropriately blended as necessary so long as the effects of the present invention are not impaired. You can also.
  • the method for producing the internal liquid composition of the present invention is not particularly limited. Usually, after dissolving each component of polyoxyethylene lauryl ether, polyoxyethylene phytosterol, or polyoxyethylene phytostanol and sparingly water-soluble vitamins, oil components or herbal extracts, and polyhydric alcohols in appropriate amounts of purified water It can be produced by adjusting the pH, adjusting the volume by adding purified water, and performing filtration and sterilization treatment as necessary.
  • Examples 1 to 4 An internal liquid composition having the formulation shown in Table 1 was produced. First, polyoxyethylene lauryl ether, tocopherol acetate and glycerin were heated and mixed at 90 ° C. and then dissolved in water at room temperature. Next, citric acid was blended, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled into glass bottles and capped to give Examples 1 to 4.
  • Examples 5 to 10 An internal liquid composition having the formulation shown in Table 2 was produced. First, polyoxyethylene phytosterol, tocopherol acetate, and glycerin were heated and mixed at 90 ° C. and then dissolved in water at room temperature. Next, citric acid was blended, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled into glass bottles and capped to give Examples 5 to 10.
  • Examples 11-18 An internal liquid composition having the formulation shown in Table 3 was produced. First, polyoxyethylene phytostanol, tocopherol acetate and glycerin were heated and mixed at 90 ° C. and then dissolved in water at room temperature. Next, citric acid was blended, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled into glass bottles and capped, and Examples 11 to 18 were made.
  • Examples 19-22 An internal liquid composition having the formulation shown in Table 4 was produced. First, a) polyoxyethylene lauryl ether, b) one or two of vitamin D, vitamin K, tocopherol acetate, and ⁇ -oryzanol, and c) glycerin or sorbitol are heated and mixed at 90 ° C. Dissolved with water. Next, citric acid was added, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled into glass bottles and capped, and Examples 19 to 22 were obtained.
  • Examples 23-26 An internal liquid composition having the formulation shown in Table 5 was produced. First, a) polyoxyethylene phytosterol, b) one or two of vitamin D, vitamin K, tocopherol acetate and ⁇ -oryzanol, and c) glycerin or sorbitol are heated and mixed at 90 ° C. Was dissolved. Next, citric acid was blended, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled into glass bottles and capped to give Examples 23 to 26.
  • Examples 27-31 An internal liquid composition having the formulation shown in Table 6 was produced. First, a) polyoxyethylene phytostanol, b) one or two of vitamin D, vitamin K, tocopherol acetate, and ⁇ -oryzanol, and c) glycerin or sorbitol are heated and mixed at 90 ° C. Dissolved with water. Next, citric acid was blended, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled in glass bottles and capped to give Examples 27 to 31.
  • Examples 32-34 An internal liquid composition having the formulation shown in Table 7 was produced. First, polyoxyethylene lauryl ether, tocopherol acetate, and glycerin were heated and mixed at 90 ° C., and then dissolved in water at room temperature. Next, any one of carrot extract, licorice extract, and chimpi extract was mixed with citric acid. The pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled into glass bottles and capped, and Examples 32 to 34 were made.
  • Examples 35-37 An internal liquid composition having the formulation shown in Table 8 was produced. First, polyoxyethylene phytosterol, tocopherol acetate, and glycerin were heated and mixed at 90 ° C. and then dissolved in water at room temperature. Next, any one of a carrot extract, a licorice extract and a chimney extract and citric acid were blended, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled into glass bottles and capped to give Examples 35 to 37.
  • Examples 38 to 40 An internal liquid composition having the formulation shown in Table 9 was produced. First, polyoxyethylene phytostanol, tocopherol acetate and glycerin were heated and mixed at 90 ° C. and then dissolved in water at room temperature. Next, any one of carrot extract, licorice extract, and chimpi extract and citric acid were blended, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled into glass bottles and capped to give Examples 38 to 40.
  • Examples 41 and 42 An internal liquid composition having the formulation shown in Table 10 was produced. First, polyoxyethylene lauryl ether, tocopherol acetate and glycerin were heated and mixed at 90 ° C. and then dissolved in water at room temperature. Next, citric acid was added, and the pH was adjusted with a 4 mol / L aqueous sodium hydroxide solution or 1 mol / L hydrochloric acid. These were filled into glass bottles and capped, and Examples 41 and 42 were obtained.
  • Examples 43 and 44 An internal liquid composition having the formulation shown in Table 11 was produced. First, polyoxyethylene phytosterol, tocopherol acetate, and glycerin were heated and mixed at 90 ° C. and then dissolved in water at room temperature. Next, citric acid was added, and the pH was adjusted with a 4 mol / L aqueous sodium hydroxide solution or 1 mol / L hydrochloric acid. These were filled in a glass bottle and capped, and Examples 43 and 44 were obtained.
  • Examples 45 and 46 An internal liquid composition having the formulation shown in Table 12 was produced. First, polyoxyethylene phytostanol, tocopherol acetate and glycerin were heated and mixed at 90 ° C. and then dissolved in water at room temperature. Next, citric acid was added, and the pH was adjusted with a 4 mol / L aqueous sodium hydroxide solution or 1 mol / L hydrochloric acid. These were filled in a glass bottle and capped, and Examples 45 and 46 were obtained.
  • Comparative Example 1 and Comparative Example 2 An internal liquid composition having the formulation shown in Table 13 was produced. First, polyoxyethylene hydrogenated castor oil, tocopherol acetate, and glycerin were heated and mixed at 90 ° C., and then dissolved in water at room temperature. Next, citric acid was blended, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled in glass bottles and capped to make Comparative Examples 1 and 2.
  • Comparative Example 3 and Comparative Example 4 An internal liquid composition having the formulation shown in Table 13 was produced. First, polyoxyethylene cetyl ether (POE (30)), tocopherol acetate and glycerin were heated and mixed at 90 ° C. and then dissolved in water at room temperature. Next, citric acid was blended, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled into glass bottles and capped to make Comparative Examples 3 to 4.
  • POE (30) polyoxyethylene cetyl ether
  • tocopherol acetate and glycerin were heated and mixed at 90 ° C. and then dissolved in water at room temperature. Next, citric acid was blended, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled into glass bottles and capped to make Comparative Examples 3 to 4.
  • Comparative Example 5 and Comparative Example 6 An internal liquid composition having the formulation shown in Table 13 was produced. First, polyoxyethylene cetyl ether (POE (40)), tocopherol acetate and glycerin were heated and mixed at 90 ° C. and then dissolved in water at room temperature. Next, citric acid was blended, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled into glass bottles and capped to make Comparative Examples 5-6.
  • POE polyoxyethylene cetyl ether
  • tocopherol acetate glycerin
  • glycerin citric acid was blended, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution.
  • Test Examples 1 to 46 and Comparative Examples 1 to 6 were stored in a constant temperature bath at 65 ° C. for 4 weeks and then cooled at 5 ° C. for 1 day (in the table, abbreviated as 65 ° C.-4 W + 5 ° C.-1D) The precipitates and suspended solids in the internal liquid composition were visually observed. The results are shown in Tables 1-13. The degree of precipitation and suspended matter was determined according to the following criteria.
  • the poorly water-soluble vitamin can be stably dissolved for a long time, and It was confirmed that no turbidity or precipitation was generated even after long-term storage.
  • the present invention it is expected to be provided as an internal solution containing a poorly water-soluble vitamin, an oil component, or a herbal extract in the field of pharmaceuticals, quasi drugs, or foods.

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Abstract

This oral liquid composition is characterized by containing a) poorly water-soluble vitamins, oil components or herbal extracts, b) one or more selected from polyoxyethylene lauryl ether, polyoxyethylene phytosterol, and polyoxyethylene phytostanol, and c) a polyvalent alcohol, wherein, even at low pH, the poorly water-soluble vitamins, oil components or herbal extracts remain stably dissolved over a long period of time without causing turbidity or precipitation.

Description

内服液体組成物Oral liquid composition
　本発明は、難水溶性ビタミン、油成分、又は生薬抽出物を液体組成物中に長期間安定に溶解した内服液体組成物に関する。 The present invention relates to a liquid composition for internal use in which a poorly water-soluble vitamin, an oil component, or a herbal extract is stably dissolved in a liquid composition for a long period of time.
　難水溶性ビタミン、油成分などの難水溶性成分や、生薬抽出物を低ｐＨ下でドリンク剤等の飲料に配合する場合、可溶化剤が必要となる。難水溶性成分に可溶化剤が必要なのは当然であるが、生薬抽出物においても、加水分解により長期的に濁りや沈殿を生じるため、可溶化剤が必要である。なお、ドリンク剤等の飲料は防腐性や風味等の観点から低ｐＨが適している。 難 Solubilizing agents are required when blending sparingly water-soluble ingredients such as sparingly water-soluble vitamins and oil ingredients and herbal extracts into beverages such as drinks at low pH. Naturally, a solubilizer is required for the poorly water-soluble component, but also in a crude drug extract, a solubilizer is necessary because it causes turbidity and precipitation in the long term due to hydrolysis. In addition, low pH is suitable for drinks, such as a drink agent, from viewpoints, such as antiseptic | preservation property and flavor.
　しかしながら、食品や医薬品等に配合される経口可能な可溶化剤の多くは、低ｐＨ領域では長期保存時に可溶化剤由来の濁りや沈殿を生じてしまうことが課題とされていた（特許文献１）。 However, many of the orally-soluble solubilizers blended in foods and pharmaceuticals have been subject to turbidity and precipitation derived from the solubilizer during long-term storage in a low pH region (Patent Document 1). ).
特開２００２－１２８７０３JP 2002-128703 A
　したがって本発明は、低ｐＨでも、濁り・沈殿を生じさせることなく、難水溶性ビタミン、油成分、又は生薬抽出物を長期間安定に溶解させた内服液体組成物を提供することを課題とする。 Accordingly, an object of the present invention is to provide an internal liquid composition in which a poorly water-soluble vitamin, oil component, or herbal extract is stably dissolved for a long period of time without causing turbidity or precipitation even at a low pH. .
　本発明者らは、かかる課題を解決すべく鋭意検討を重ねた結果、可溶化剤としてポリオキシエチレンラウリルエーテル、ポリオキシエチレンフィトステロール、及びポリオキシエチレンフィトスタノールから選ばれる１種以上を用い、さらに多価アルコール類を配合することで、難水溶性ビタミン、油成分、又は生薬抽出物を長期間安定に溶解させることができることを見出した。 As a result of intensive studies to solve such problems, the present inventors used one or more selected from polyoxyethylene lauryl ether, polyoxyethylene phytosterol, and polyoxyethylene phytostanol as a solubilizer, It has been found that a poorly water-soluble vitamin, an oil component, or a herbal extract can be stably dissolved for a long period of time by blending polyhydric alcohols.
　かかる知見に基づき完成した本発明の態様は、
（１）ａ）難水溶性ビタミン、油成分、及び生薬抽出物から選ばれる１種以上、ｂ）ポリオキシエチレンラウリルエーテル、ポリオキシエチレンフィトステロール、及びポリオキシエチレンフィトスタノールから選ばれる１種以上、及びｃ）多価アルコール類、を含有することを特徴とする内服液体組成物、
（２）ｐＨが２．０～４．０である（１）に記載の内服液体組成物、
（３）多価アルコール類としてグリセリン、及びソルビトールから選ばれる１種以上を含有する（１）又は（２）に記載の内服液体組成物、
（４）ｂ）及びｃ）成分の配合量が、ａ）成分の配合量１質量部に対して０．０２～５００質量部である（１）～（３）のいずれか１項に記載の内服液体組成物、
である。 The aspect of the present invention completed based on such findings is as follows.
(1) a) one or more selected from poorly water-soluble vitamins, oil components, and herbal extracts, b) one or more selected from polyoxyethylene lauryl ether, polyoxyethylene phytosterol, and polyoxyethylene phytostanol, And c) a polyhydric alcohol, an internal liquid composition,
(2) The internal liquid composition according to (1), wherein the pH is 2.0 to 4.0,
(3) The internal liquid composition according to (1) or (2), which contains at least one selected from glycerin and sorbitol as polyhydric alcohols,
(4) The blending amount of the components b) and c) is 0.02 to 500 parts by mass with respect to 1 part by mass of the component a), according to any one of (1) to (3) Oral liquid composition,
It is.
　本発明により、難水溶性ビタミン、油成分、又は生薬抽出物を長期間安定に溶解させる透明な内服液体組成物を得ることができる。 According to the present invention, it is possible to obtain a transparent oral liquid composition that can dissolve a poorly water-soluble vitamin, an oil component, or a herbal extract stably for a long period of time.
　本発明で用いる難水溶性ビタミンとは、内服可能な難水溶性ビタミンをいい、例えばビタミンＥ、ビタミンＥ脂肪酸エステル等のビタミンＥ誘導体（例えば、酢酸トコフェロール）、ビタミンＡ、ビタミンＤ、ビタミンＫが挙げられる。油成分とは生理活性を有する脂溶性物質や香料（合成香料・天然香料）、精油類であって内服可能なものをいい、生理活性を有する脂溶性物質とは例えばγ－オリザノール、γ－リノレン酸、ルテイン、ポリコサノール、ＣｏＱ１０、セラミド、レスベラトロール、アスタキサンチン、アマニ油、ＥＰＡ、トウガラシ抽出物や胡椒抽出物等であり、香料（合成香料・天然香料）、精油類とは例えばシトラール、リモネン等の合成或いは天然由来の香料または精油類が挙げられる。難水溶性ビタミン、油成分は単独で配合してもよく、２種以上を組み合わせて配合してもよい。内服液体組成物中へのこれらの配合量は特に限定されないが、好ましくは０．０００１乃至１質量％、より好ましくは０．００１乃至０．５質量％、もっとも好ましくは０．００２乃至０．０５質量％である。 The sparingly water-soluble vitamin used in the present invention refers to a sparingly water-soluble vitamin that can be taken internally, such as vitamin E, vitamin E derivatives such as vitamin E fatty acid esters (for example, tocopherol acetate), vitamin A, vitamin D, and vitamin K. Can be mentioned. The oil component means a fat-soluble substance having a biological activity, a fragrance (synthetic fragrance or natural fragrance), or an essential oil that can be taken internally. Examples of the fat-soluble substance having a physiological activity include γ-oryzanol and γ-linolene. Acid, lutein, policosanol, CoQ10, ceramide, resveratrol, astaxanthin, linseed oil, EPA, pepper extract, pepper extract, etc. Examples of fragrances (synthetic fragrances / natural fragrances) and essential oils include citral, limonene, etc. Or natural-derived fragrances or essential oils. The poorly water-soluble vitamin and oil component may be blended alone or in combination of two or more. The blending amount of these in the internal liquid composition is not particularly limited, but is preferably 0.0001 to 1% by mass, more preferably 0.001 to 0.5% by mass, and most preferably 0.002 to 0.05%. % By mass.
　本発明で用いる生薬抽出物はエキス末、抽出エキス、流エキスなどであるが、内服可能であれば特に限定されることはなく、生薬としてはニンジン、オウギ、オウセイ、カンゾウ、タイソウ、チンピ、ビャクジュツ、サンヤク、ブクリョウ、シュクシャ、ジオウ、トウキ、クコシ、カシュウ、リュウガンニク、シャクヤク、センキュウ、ニクジュヨウ、ジャショウシ、トシシ、トチュウ、ロクジョウ、イカリソウ、カイクジン、トウチュウカソウ、カイバ、オンジ、ヨクイニン、サンシュユ、ゴミシ、ショウキョウ、サイコ、ケイヒ、ハンピ、ムイラプアマ、バクモンドウ、ゴオウ、ジョテイシなどが挙げられる。これらは単独で配合してもよく、２種以上を組み合わせて配合してもよい。内服液体組成物中へのこれらの配合量は特に限定されないが、好ましくは０．０００１乃至１質量％、より好ましくは０．００１乃至０．５質量％、もっとも好ましくは０．００２乃至０．０５質量％である。 Herbal extracts used in the present invention are extract powder, extract extract, flow extract, etc., but are not particularly limited as long as they can be taken orally, and herbal medicines include carrots, rouges, scallions, licorice, taisou, chimpi, sandalwood. , Sanyaku, Bukuryo, Shukusha, Ziou, Touki, Kokushi, Kashu, Ryuganiku, Peonies, Senkyu, Nikujuyo, Jashoushi, Toshishi, Tochu, Rokujou, Ikarisou, Kaikujin, Tochuukaso, Kaiba, Onji, Yakuinin , Psycho, Keihi, Hampi, Muirapuama, Bakumondo, Gooh, and Joteishi. These may be blended singly or in combination of two or more. The blending amount of these in the internal liquid composition is not particularly limited, but is preferably 0.0001 to 1% by mass, more preferably 0.001 to 0.5% by mass, and most preferably 0.002 to 0.05%. % By mass.
　本発明で用いるポリオキシエチレンラウリルエーテルはオキシエチレンの付加モル数が５～５０モルであり、ポリオキシエチレンフィトステロール、ポリオキシエチレンフィトスタノールはオキシエチレンの付加モル数が５～５０モルであるポリオキシエチレンフィトステロールである。具体的には、ポリオキシエチレン（２５モル）ラウリルエーテル、ポリオキシエチレン（５モル）フィトステロール、ポリオキシエチレン（１０モル）フィトステロール、ポリオキシエチレン（２０モル）フィトステロール、ポリオキシエチレン（３０モル）フィトステロール、ポリオキシエチレン（２５モル）フィトスタノール等が挙げられ、これらは単独で配合してもよく、２種以上を組み合わせて配合してもよい。 The polyoxyethylene lauryl ether used in the present invention has an addition mole number of oxyethylene of 5 to 50 moles, and the polyoxyethylene phytosterol and polyoxyethylene phytostanol have a polyoxyethylene addition mole number of 5 to 50 moles. Ethylene phytosterol. Specifically, polyoxyethylene (25 mol) lauryl ether, polyoxyethylene (5 mol) phytosterol, polyoxyethylene (10 mol) phytosterol, polyoxyethylene (20 mol) phytosterol, polyoxyethylene (30 mol) phytosterol , Polyoxyethylene (25 mol) phytostanol, and the like. These may be used alone or in combination of two or more.
　ポリオキシエチレンラウリルエーテル、ポリオキシエチレンフィトステロール、及びポリオキシエチレンフィトスタノールから選ばれる１種以上の配合量は特に限定されないが、難水溶性ビタミン、油成分、及び生薬抽出物から選ばれる１種以上の１質量部に対して通常は０．０２～５００質量部、好ましくは０．０５～２００質量部、より好ましくは０．５～１００質量部である。ポリオキシエチレンラウリルエーテル、ポリオキシエチレンフィトステロール、又はポリオキシエチレンフィトスタノールの配合量が少ないと濁りや沈殿を生成し、商品性が良くかつ安定な液体組成物を得ることができないことがある。 The amount of one or more selected from polyoxyethylene lauryl ether, polyoxyethylene phytosterol, and polyoxyethylene phytostanol is not particularly limited, but one or more selected from poorly water-soluble vitamins, oil components, and herbal extracts The amount is usually 0.02 to 500 parts by mass, preferably 0.05 to 200 parts by mass, and more preferably 0.5 to 100 parts by mass with respect to 1 part by mass. If the amount of polyoxyethylene lauryl ether, polyoxyethylene phytosterol, or polyoxyethylene phytostanol is too small, turbidity and precipitation may be generated, and a liquid composition with good commercial properties and stability may not be obtained.
　本発明で用いる多価アルコール類としては、例えばエチレングリコール、プロピレングリコール、１、３－ブチレングリコール、ジプロピレングリコール、イソプレングリコール、ポリエチレングリコール、グリセリン、ポリグリセリン、ジグリセリン、及びソルビトールから選ばれる１種以上が挙げられる。これらの中でグリセリン、及びソルビトールから選ばれる１種以上が好ましく、多価アルコール類の配合量は特に限定されないが、難水溶性ビタミン、油成分、及び生薬抽出物から選ばれる１種以上の１質量部に対して通常は０．０２～５００質量部、好ましくは０．０５～２００質量部、より好ましくは１～１００質量部である。 Examples of the polyhydric alcohol used in the present invention include one selected from ethylene glycol, propylene glycol, 1,3-butylene glycol, dipropylene glycol, isoprene glycol, polyethylene glycol, glycerin, polyglycerin, diglycerin, and sorbitol. The above is mentioned. Among these, at least one selected from glycerin and sorbitol is preferable, and the blending amount of polyhydric alcohols is not particularly limited, but at least one selected from poorly water-soluble vitamins, oil components, and herbal extracts. The amount is usually 0.02 to 500 parts by mass, preferably 0.05 to 200 parts by mass, and more preferably 1 to 100 parts by mass with respect to parts by mass.
　本発明の内服液体組成物は長期間保管後も透明な状態であり、更には長期間保管後の低温環境下でも沈殿物が生じずに透明な状態が維持された。ここで、低温とは好ましくは１０℃以下を意味し、さらに好ましくは５℃以下である。 The oral liquid composition of the present invention was in a transparent state even after long-term storage, and further maintained in a transparent state without precipitation even in a low-temperature environment after long-term storage. Here, the low temperature preferably means 10 ° C. or less, more preferably 5 ° C. or less.
　本発明の内服液体組成物のｐＨは、風味の点及び防腐性の点から２．０～４．０が好ましい。ｐＨの調整には、例えば、クエン酸、リンゴ酸、フマル酸、酒石酸、乳酸及びコハク酸などの有機酸、又はこれら有機酸の塩、リン酸、塩酸などの無機酸、水酸化ナトリウムなどの無機塩基を用いることができる。本発明の内服液体組成物は、医薬品及び医薬部外品の他、栄養機能性食品、特定保険用食品等の食品領域における内服液剤として利用できる。 The pH of the internal liquid composition of the present invention is preferably 2.0 to 4.0 from the viewpoint of flavor and antiseptic properties. For adjusting the pH, for example, organic acids such as citric acid, malic acid, fumaric acid, tartaric acid, lactic acid and succinic acid, or salts of these organic acids, inorganic acids such as phosphoric acid and hydrochloric acid, inorganic acids such as sodium hydroxide, etc. A base can be used. The liquid composition for internal use of the present invention can be used as a liquid preparation for internal use in food fields such as nutritional functional food and food for specified insurance, in addition to pharmaceuticals and quasi drugs.
　本発明の内服液体組成物には、水溶性ビタミン類、ミネラル類、アミノ酸類、ローヤルゼリー、カフェインなどを本発明の効果を損なわない範囲で適宜に配合できる。また、必要に応じて抗酸化剤、着色剤、香料、矯味剤、界面活性剤、溶解補助剤、保存剤、甘味料などの添加物を本発明の効果を損なわない範囲で適宜に配合することもできる。 In the liquid composition for internal use of the present invention, water-soluble vitamins, minerals, amino acids, royal jelly, caffeine and the like can be appropriately blended as long as the effects of the present invention are not impaired. In addition, additives such as antioxidants, colorants, fragrances, flavoring agents, surfactants, solubilizers, preservatives, sweeteners, and the like are appropriately blended as necessary so long as the effects of the present invention are not impaired. You can also.
　本発明の内服液体組成物を製造する方法は特に限定されるものではない。通常、ポリオキシエチレンラウリルエーテル、ポリオキシエチレンフィトステロール、又はポリオキシエチレンフィトスタノールと難水溶性ビタミン、油成分、又は生薬抽出物、及び多価アルコール類の各成分を適量の精製水に溶解した後、ｐＨを調整し、更に精製水を加えて容量調整し、必要に応じて濾過、滅菌処理を施すことにより、製造することができる。 The method for producing the internal liquid composition of the present invention is not particularly limited. Usually, after dissolving each component of polyoxyethylene lauryl ether, polyoxyethylene phytosterol, or polyoxyethylene phytostanol and sparingly water-soluble vitamins, oil components or herbal extracts, and polyhydric alcohols in appropriate amounts of purified water It can be produced by adjusting the pH, adjusting the volume by adding purified water, and performing filtration and sterilization treatment as necessary.
　以下に、実施例、比較例、及び試験例を挙げ、本発明をより詳細に説明する．
実施例１～４
　表１に示す処方の内服液体組成物を製造した。まず、ポリオキシエチレンラウリルエーテル、酢酸トコフェロール、グリセリンを９０℃にて加温混合した後、常温の水により溶解した。次にクエン酸を配合し、４ｍｏｌ／Ｌの水酸化ナトリウム水溶液によりｐＨを調整した。これらをガラス瓶に充填し、キャップを施し、実施例１～４とした。 Hereinafter, the present invention will be described in more detail with reference to examples, comparative examples, and test examples.
Examples 1 to 4
An internal liquid composition having the formulation shown in Table 1 was produced. First, polyoxyethylene lauryl ether, tocopherol acetate and glycerin were heated and mixed at 90 ° C. and then dissolved in water at room temperature. Next, citric acid was blended, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled into glass bottles and capped to give Examples 1 to 4.
実施例５～１０
　表２に示す処方の内服液体組成物を製造した。まず、ポリオキシエチレンフィトステロール、酢酸トコフェロール、グリセリンを９０℃にて加温混合した後、常温の水により溶解した。次にクエン酸を配合し、４ｍｏｌ／Ｌの水酸化ナトリウム水溶液によりｐＨを調整した。これらをガラス瓶に充填し、キャップを施し、実施例５～１０とした。 Examples 5 to 10
An internal liquid composition having the formulation shown in Table 2 was produced. First, polyoxyethylene phytosterol, tocopherol acetate, and glycerin were heated and mixed at 90 ° C. and then dissolved in water at room temperature. Next, citric acid was blended, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled into glass bottles and capped to give Examples 5 to 10.
実施例１１～１８
　表３に示す処方の内服液体組成物を製造した。まず、ポリオキシエチレンフィトスタノール、酢酸トコフェロール、グリセリンを９０℃にて加温混合した後、常温の水により溶解した。次にクエン酸を配合し、４ｍｏｌ／Ｌの水酸化ナトリウム水溶液によりｐＨを調整した。これらをガラス瓶に充填し、キャップを施し、実施例１１～１８とした。 Examples 11-18
An internal liquid composition having the formulation shown in Table 3 was produced. First, polyoxyethylene phytostanol, tocopherol acetate and glycerin were heated and mixed at 90 ° C. and then dissolved in water at room temperature. Next, citric acid was blended, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled into glass bottles and capped, and Examples 11 to 18 were made.
実施例１９～２２
　表４に示す処方の内服液体組成物を製造した。まず、ａ）ポリオキシエチレンラウリルエーテル、ｂ）ビタミンＤ、ビタミンＫ、酢酸トコフェロール、γ－オリザノールのうち１種または２種、ｃ）グリセリンまたはソルビトールを９０℃にて加温混合した後、常温の水により溶解した。次にクエン酸を配合し、４ｍｏｌ／Ｌの水酸化ナトリウム水溶液により　ｐＨを調整した。これらをガラス瓶に充填し、キャップを施し、実施例１９～２２とした。 Examples 19-22
An internal liquid composition having the formulation shown in Table 4 was produced. First, a) polyoxyethylene lauryl ether, b) one or two of vitamin D, vitamin K, tocopherol acetate, and γ-oryzanol, and c) glycerin or sorbitol are heated and mixed at 90 ° C. Dissolved with water. Next, citric acid was added, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled into glass bottles and capped, and Examples 19 to 22 were obtained.
実施例２３～２６
　表５に示す処方の内服液体組成物を製造した。まず、ａ）　ポリオキシエチレンフィトステロール、ｂ）ビタミンＤ、ビタミンＫ、酢酸トコフェロール、γ－オリザノールのうち１種または２種、ｃ）グリセリンまたはソルビトールを９０℃にて加温混合した後、常温の水により溶解した。次にクエン酸を配合し、４ｍｏｌ／Ｌの水酸化ナトリウム水溶液によりｐＨを調整した。これらをガラス瓶に充填し、キャップを施し、実施例２３～２６とした。 Examples 23-26
An internal liquid composition having the formulation shown in Table 5 was produced. First, a) polyoxyethylene phytosterol, b) one or two of vitamin D, vitamin K, tocopherol acetate and γ-oryzanol, and c) glycerin or sorbitol are heated and mixed at 90 ° C. Was dissolved. Next, citric acid was blended, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled into glass bottles and capped to give Examples 23 to 26.
実施例２７～３１
　表６に示す処方の内服液体組成物を製造した。まず、ａ）　ポリオキシエチレンフィトスタノール、ｂ）ビタミンＤ、ビタミンＫ、酢酸トコフェロール、γ－オリザノールのうち１種または２種、ｃ）グリセリンまたはソルビトールを９０℃にて加温混合した後、常温の水により溶解した。次にクエン酸を配合し、４ｍｏｌ／Ｌの水酸化ナトリウム水溶液によりｐＨを調整した。これらをガラス瓶に充填し、キャップを施し、実施例２７～３１とした。 Examples 27-31
An internal liquid composition having the formulation shown in Table 6 was produced. First, a) polyoxyethylene phytostanol, b) one or two of vitamin D, vitamin K, tocopherol acetate, and γ-oryzanol, and c) glycerin or sorbitol are heated and mixed at 90 ° C. Dissolved with water. Next, citric acid was blended, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled in glass bottles and capped to give Examples 27 to 31.
実施例３２～３４
　表７に示す処方の内服液体組成物を製造した。まず、ポリオキシエチレンラウリルエーテル、酢酸トコフェロール、グリセリンを９０℃にて加温混合した後、常温の水により溶解した、次にニンジンエキス、カンゾウエキス、チンピエキスのいずれか１種とクエン酸を配合し、４ｍｏｌ／Ｌの水酸化ナトリウム水溶液によりｐＨを調整した。これらをガラス瓶に充填し、キャップを施し、実施例３２～３４とした。 Examples 32-34
An internal liquid composition having the formulation shown in Table 7 was produced. First, polyoxyethylene lauryl ether, tocopherol acetate, and glycerin were heated and mixed at 90 ° C., and then dissolved in water at room temperature. Next, any one of carrot extract, licorice extract, and chimpi extract was mixed with citric acid. The pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled into glass bottles and capped, and Examples 32 to 34 were made.
実施例３５～３７
　表８に示す処方の内服液体組成物を製造した。まず、ポリオキシエチレンフィトステロール、酢酸トコフェロール、グリセリンを９０℃にて加温混合した後、常温の水により溶解した。次にニンジンエキス、カンゾウエキス、チンピエキスのいずれか１種とクエン酸を配合し、４ｍｏｌ／Ｌの水酸化ナトリウム水溶液によりｐＨを調整した。これらをガラス瓶に充填し、キャップを施し、実施例３５～３７とした。 Examples 35-37
An internal liquid composition having the formulation shown in Table 8 was produced. First, polyoxyethylene phytosterol, tocopherol acetate, and glycerin were heated and mixed at 90 ° C. and then dissolved in water at room temperature. Next, any one of a carrot extract, a licorice extract and a chimney extract and citric acid were blended, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled into glass bottles and capped to give Examples 35 to 37.
実施例３８～４０
　表９に示す処方の内服液体組成物を製造した。まず、ポリオキシエチレンフィトスタノール、酢酸トコフェロール、グリセリンを９０℃にて加温混合した後、常温の水により溶解した。次にニンジンエキス、カンゾウエキス、チンピエキスのいずれか１種とクエン酸を配合し、４ｍｏｌ／Ｌの水酸化ナトリウム水溶液によりｐＨを調整した。これらをガラス瓶に充填し、キャップを施し、実施例３８～４０とした。 Examples 38 to 40
An internal liquid composition having the formulation shown in Table 9 was produced. First, polyoxyethylene phytostanol, tocopherol acetate and glycerin were heated and mixed at 90 ° C. and then dissolved in water at room temperature. Next, any one of carrot extract, licorice extract, and chimpi extract and citric acid were blended, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled into glass bottles and capped to give Examples 38 to 40.
実施例４１、４２
　表１０に示す処方の内服液体組成物を製造した。まず、ポリオキシエチレンラウリルエーテル、酢酸トコフェロール、グリセリンを９０℃にて加温混合した後、常温の水により溶解した。次にクエン酸を配合し、４ｍｏｌ／Ｌの水酸化ナトリウム水溶液または１ｍｏｌ／Ｌの塩酸によりｐＨを調整した。これらをガラス瓶に充填し、キャップを施し、実施例４１、４２とした。 Examples 41 and 42
An internal liquid composition having the formulation shown in Table 10 was produced. First, polyoxyethylene lauryl ether, tocopherol acetate and glycerin were heated and mixed at 90 ° C. and then dissolved in water at room temperature. Next, citric acid was added, and the pH was adjusted with a 4 mol / L aqueous sodium hydroxide solution or 1 mol / L hydrochloric acid. These were filled into glass bottles and capped, and Examples 41 and 42 were obtained.
実施例４３、４４
　表１１に示す処方の内服液体組成物を製造した。まず、ポリオキシエチレンフィトステロール、酢酸トコフェロール、グリセリンを９０℃にて加温混合した後、常温の水により溶解した。次にクエン酸を配合し、４ｍｏｌ／Ｌの水酸化ナトリウム水溶液または１ｍｏｌ／Ｌの塩酸によりｐＨを調整した。これらをガラス瓶に充填し、キャップを施し、実施例４３、４４とした。 Examples 43 and 44
An internal liquid composition having the formulation shown in Table 11 was produced. First, polyoxyethylene phytosterol, tocopherol acetate, and glycerin were heated and mixed at 90 ° C. and then dissolved in water at room temperature. Next, citric acid was added, and the pH was adjusted with a 4 mol / L aqueous sodium hydroxide solution or 1 mol / L hydrochloric acid. These were filled in a glass bottle and capped, and Examples 43 and 44 were obtained.
実施例４５、４６
　表１２に示す処方の内服液体組成物を製造した。まず、ポリオキシエチレンフィトスタノール、酢酸トコフェロール、グリセリンを９０℃にて加温混合した後、常温の水により溶解した。次にクエン酸を配合し、４ｍｏｌ／Ｌの水酸化ナトリウム水溶液または１ｍｏｌ／Ｌの塩酸によりｐＨを調整した。これらをガラス瓶に充填し、キャップを施し、実施例４５、４６とした。 Examples 45 and 46
An internal liquid composition having the formulation shown in Table 12 was produced. First, polyoxyethylene phytostanol, tocopherol acetate and glycerin were heated and mixed at 90 ° C. and then dissolved in water at room temperature. Next, citric acid was added, and the pH was adjusted with a 4 mol / L aqueous sodium hydroxide solution or 1 mol / L hydrochloric acid. These were filled in a glass bottle and capped, and Examples 45 and 46 were obtained.
比較例１及び比較例２
　表１３に示す処方の内服液体組成物を製造した。まず、ポリオキシエチレン硬化ヒマシ油、酢酸トコフェロール、グリセリンを９０℃にて加温混合した後、常温の水により溶解した。次にクエン酸を配合し、４ｍｏｌ／Ｌの水酸化ナトリウム水溶液によりｐＨを調整した。これらをガラス瓶に充填し、キャップを施し、比較例１～２とした。 Comparative Example 1 and Comparative Example 2
An internal liquid composition having the formulation shown in Table 13 was produced. First, polyoxyethylene hydrogenated castor oil, tocopherol acetate, and glycerin were heated and mixed at 90 ° C., and then dissolved in water at room temperature. Next, citric acid was blended, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled in glass bottles and capped to make Comparative Examples 1 and 2.
比較例３及び比較例４
　表１３に示す処方の内服液体組成物を製造した。まず、ポリオキシエチレンセチルエーテル（ＰＯＥ（３０））、酢酸トコフェロール、グリセリンを９０℃にて加温混合した後、常温の水により溶解した。次にクエン酸を配合し、４ｍｏｌ／Ｌの水酸化ナトリウム水溶液によりｐＨを調整した。これらをガラス瓶に充填し、キャップを施し、比較例３～４とした。 Comparative Example 3 and Comparative Example 4
An internal liquid composition having the formulation shown in Table 13 was produced. First, polyoxyethylene cetyl ether (POE (30)), tocopherol acetate and glycerin were heated and mixed at 90 ° C. and then dissolved in water at room temperature. Next, citric acid was blended, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled into glass bottles and capped to make Comparative Examples 3 to 4.
比較例５及び比較例６
　表１３に示す処方の内服液体組成物を製造した。まず、ポリオキシエチレンセチルエーテル（ＰＯＥ（４０））、酢酸トコフェロール、グリセリンを９０℃にて加温混合した後、常温の水により溶解した。次にクエン酸を配合し、４ｍｏｌ／Ｌの水酸化ナトリウム水溶液によりｐＨを調整した。これらをガラス瓶に充填し、キャップを施し、比較例５～６とした。 Comparative Example 5 and Comparative Example 6
An internal liquid composition having the formulation shown in Table 13 was produced. First, polyoxyethylene cetyl ether (POE (40)), tocopherol acetate and glycerin were heated and mixed at 90 ° C. and then dissolved in water at room temperature. Next, citric acid was blended, and the pH was adjusted with a 4 mol / L sodium hydroxide aqueous solution. These were filled into glass bottles and capped to make Comparative Examples 5-6.
試験例
　実施例１～４６、及び比較例１～６を６５℃の恒温槽中で４週間保存後、５℃で１日冷却し（表中では６５℃－４Ｗ＋５℃－１Ｄと略記する）、内服液体組成物中の沈殿及び浮遊物を目視により観察した。結果を表１～１３に示す。なお、沈殿及び浮遊物の程度は以下の基準により判定した。 Test Examples Examples 1 to 46 and Comparative Examples 1 to 6 were stored in a constant temperature bath at 65 ° C. for 4 weeks and then cooled at 5 ° C. for 1 day (in the table, abbreviated as 65 ° C.-4 W + 5 ° C.-1D) The precipitates and suspended solids in the internal liquid composition were visually observed. The results are shown in Tables 1-13. The degree of precipitation and suspended matter was determined according to the following criteria.
　性状の観察基準
　　不溶物なし　　　：　－
　　不溶物少量あり　：　＋
　　不溶物多量にあり：＋＋ Observation criteria for properties No insoluble matter:-
There is a small amount of insoluble matter: +
There is a large amount of insoluble matter: ++
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000005
Figure JPOXMLDOC01-appb-T000005
Figure JPOXMLDOC01-appb-T000006
Figure JPOXMLDOC01-appb-T000006
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
Figure JPOXMLDOC01-appb-T000013
Figure JPOXMLDOC01-appb-T000013
　以上の結果より、ポリオキシエチレンラウリルエーテル、ポリオキシエチレンフィトステロール、及びポリオキシエチレンフィトスタノールから選ばれる１種以上を配合することで、難水溶性ビタミンを長期間安定に溶解させることができ、かつ長期間保管しても濁りや沈殿を生成しないことを確認した。 From the above results, by blending one or more selected from polyoxyethylene lauryl ether, polyoxyethylene phytosterol, and polyoxyethylene phytostanol, the poorly water-soluble vitamin can be stably dissolved for a long time, and It was confirmed that no turbidity or precipitation was generated even after long-term storage.
　本発明により、医薬品、医薬部外品、又は食品の分野において難水溶性ビタミン、油成分、又は生薬抽出物を含有する内服液剤として提供することが期待される。 According to the present invention, it is expected to be provided as an internal solution containing a poorly water-soluble vitamin, an oil component, or a herbal extract in the field of pharmaceuticals, quasi drugs, or foods.

Claims (4)

  1. ａ）難水溶性ビタミン、油成分、及び生薬抽出物から選ばれる１種以上、ｂ）ポリオキシエチレンラウリルエーテル、ポリオキシエチレンフィトステロール、及びポリオキシエチレンフィトスタノールから選ばれる１種以上、及びｃ）多価アルコール類、を含有することを特徴とする内服液体組成物。 a) one or more selected from poorly water-soluble vitamins, oil components, and herbal extracts, b) one or more selected from polyoxyethylene lauryl ether, polyoxyethylene phytosterol, and polyoxyethylene phytostanol, and c) An internal liquid composition comprising a polyhydric alcohol.
  2. ｐＨが２．０～４．０である請求項１に記載の内服液体組成物。 The liquid composition for internal use according to claim 1, which has a pH of 2.0 to 4.0.
  3. 多価アルコール類としてグリセリン、及びソルビトールから選ばれる１種以上を含有する請求項１又は２に記載の内服液体組成物。 The internal liquid composition of Claim 1 or 2 containing 1 or more types chosen from glycerol and sorbitol as a polyhydric alcohol.
  4. ｂ）及びｃ）成分の配合量が、ａ）成分の配合量１質量部に対して０．０２～５００質量部である請求項１～３のいずれか１項に記載の内服液体組成物。 The internal liquid composition according to any one of claims 1 to 3, wherein the blending amount of the components b) and c) is 0.02 to 500 parts by mass with respect to 1 part by mass of the component a).
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