JP6372558B2 - Oral solution - Google Patents
Oral solution Download PDFInfo
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- JP6372558B2 JP6372558B2 JP2016504095A JP2016504095A JP6372558B2 JP 6372558 B2 JP6372558 B2 JP 6372558B2 JP 2016504095 A JP2016504095 A JP 2016504095A JP 2016504095 A JP2016504095 A JP 2016504095A JP 6372558 B2 JP6372558 B2 JP 6372558B2
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- ambroxol hydrochloride
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- 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
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
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- 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
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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- 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
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
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- 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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/10—Expectorants
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
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- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
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- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pulmonology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Emergency Medicine (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
本発明は、塩酸アンブロキソールを含有する内服液剤に関する。 The present invention relates to an internal solution containing ambroxol hydrochloride.
塩酸アンブロキソールは気道液分泌促進作用、肺サーファクタント分泌促進作用及び線毛運動の活発化により、気道壁を潤滑にして痰や膿を排出しやすくする気道潤滑去痰剤であり、錠剤のほか、細粒や液剤、シロップ剤、持続性のある徐放カプセルなど様々な剤型で用いられている。 Ambroxol hydrochloride is an airway lubrication expectorant that lubricates the airway wall and facilitates discharge of sputum and pus by promoting airway fluid secretion promoting action, lung surfactant secretion promoting action and ciliary movement, in addition to tablets, It is used in various dosage forms such as fine granules, liquids, syrups, and sustained sustained release capsules.
塩酸アンブロキソールを含有する去痰薬は、服用しやすさの観点から内服液剤や小児用シロップ剤として広く受け入れられている。 An expectorant containing ambroxol hydrochloride is widely accepted as a liquid for internal use and a syrup for children from the viewpoint of ease of taking.
しかしながら、塩酸アンブロキソールを含有する水性液剤は、光照射により着色が認められるため、外観が変化してしまうという問題がある。外観の変化を抑制するためには、光照射を抑制することで着色を抑える方法や、光照射による反応前の溶液を着色することで色の変化率を小さくする方法が考えられる。 However, an aqueous liquid preparation containing ambroxol hydrochloride has a problem that its appearance changes because it is colored by light irradiation. In order to suppress the change in appearance, there are a method of suppressing coloring by suppressing light irradiation, and a method of decreasing the color change rate by coloring a solution before reaction by light irradiation.
光照射を抑制する方法としては褐色ガラス瓶等の遮光容器を用いる方法があるが、薬液の状態を観察するのは困難である。また、ガラス瓶は重量の面から持ち運びの点で不便であるが、その他の解決方法はなく、塩酸アンブロキソールを有効成分とする水性液剤に対する光照射を抑制する手段としては遮光容器による方法が広く選択されている。 As a method for suppressing light irradiation, there is a method using a light-shielding container such as a brown glass bottle, but it is difficult to observe the state of the chemical solution. In addition, the glass bottle is inconvenient in terms of weight, but there is no other solution, and a method using a light-shielding container is widely used as a means for suppressing light irradiation with respect to an aqueous liquid agent containing ambroxol hydrochloride as an active ingredient. Is selected.
また、製剤を着色するのに使用する色素については、塩酸アンブロキソールと黄色５号（サンセットイエローＦＣＦ）を同時に配合した場合に、沈殿を生成することが知られている（非特許文献１）。 Moreover, about the pigment | dye used for coloring a formulation, when ambroxol hydrochloride and yellow No. 5 (sunset yellow FCF) are mix | blended simultaneously, it is known that a precipitation will be produced | generated (nonpatent literature 1). ).
本発明は、塩酸アンブロキソールの光照射による色変化を抑制し、且つ沈殿を生成することなく安定な内服液剤を提供することを課題とする。 An object of the present invention is to provide a stable oral solution that suppresses color change due to light irradiation of ambroxol hydrochloride and does not generate a precipitate.
本発明者らは、上記課題を解決すべく鋭意検討した結果、特定の色素であるタートラジンが塩酸アンブロキソールの光照射による色変化を抑制し、且つ沈殿を生成せずに安定的に液剤に配合できることを発見し、本発明を完成するに至った。 As a result of intensive studies to solve the above problems, the present inventors have determined that tartrazine, which is a specific pigment, suppresses color change due to light irradiation of ambroxol hydrochloride, and can be stably used as a liquid without forming a precipitate. It discovered that it could mix | blend and came to complete this invention.
即ち本発明には下記が含まれる。
（１）塩酸アンブロキソール及びタートラジンを含有することを特徴とする内服液剤。
（２）塩酸アンブロキソールの含有量が液剤全量に対して０．１〜５質量％である（１）に記載の内服液剤。
（３）タートラジンの含有量が塩酸アンブロキソール１質量部に対して０．０００１〜０．１質量部である（１）又は（２）に記載の内服液剤。That is, the present invention includes the following.
(1) An internal liquid preparation containing ambroxol hydrochloride and tartrazine.
(2) The internal use liquid agent as described in (1) whose content of ambroxol hydrochloride is 0.1-5 mass% with respect to the liquid agent whole quantity.
(3) The internal liquid preparation according to (1) or (2), wherein the content of tartrazine is 0.0001 to 0.1 parts by mass with respect to 1 part by mass of ambroxol hydrochloride.
本発明により、塩酸アンブロキソール含有液剤に安定して色素を配合し、色変化を抑制した内服液剤を提供することが可能になった。 According to the present invention, it is possible to provide an internal use liquid preparation in which a pigment is stably blended in an ambroxol hydrochloride-containing liquid preparation and color change is suppressed.
本発明に用いる塩酸アンブロキソールの含有量は、液剤全量に対し、好ましくは０．１〜５質量％であり、塩酸アンブロキソールの投与量と製剤の風味の点から０．２〜１質量％がより好ましい。 The content of ambroxol hydrochloride used in the present invention is preferably 0.1 to 5% by mass with respect to the total amount of the liquid, and is 0.2 to 1% by mass from the dosage of ambroxol hydrochloride and the flavor of the preparation. % Is more preferable.
本発明に用いるタートラジンは、通常食品や医薬品に用いられる色素を指し、日本では黄色４号、アメリカではＦＤ＆Ｃ Ｙｅｌｌｏｗ Ｎｏ．５、ＥＵではＥ１０２として認可されているものである。本発明に用いるタートラジンの配合量は、塩酸アンブロキソール１質量部に対して好ましくは０．０００１〜０．１質量部であり，さらに好ましくは０．０００５〜０．００５質量部である。０．０００１質量部より少ないと十分な着色抑制効果が得られないことがあり、０．１質量部より多いと安全性等の点から好ましくないこともあり得る。 Tartrazine used in the present invention refers to a dye usually used in foods and pharmaceuticals, yellow No. 4 in Japan, and FD & C Yellow No. in the United States. 5. EU is authorized as E102. The amount of tartrazine used in the present invention is preferably 0.0001 to 0.1 parts by mass, more preferably 0.0005 to 0.005 parts by mass with respect to 1 part by mass of ambroxol hydrochloride. When the amount is less than 0.0001 part by mass, a sufficient coloring suppression effect may not be obtained, and when the amount is more than 0.1 part by mass, it may be undesirable from the viewpoint of safety.
本発明の内服液剤のｐＨは、好ましくは２．０〜７．０であり、より好ましくは３．０〜５．０である。なお、本発明の液剤のｐＨを上記範囲に保つために、必要に応じてｐＨ調整剤を配合することもできる。ｐＨ調整剤としては、クエン酸、リンゴ酸、フマル酸、酒石酸、乳酸、コハク酸などの有機酸及びそれらの塩類、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などが挙げられる。 The pH of the internal liquid preparation of this invention becomes like this. Preferably it is 2.0-7.0, More preferably, it is 3.0-5.0. In addition, in order to keep pH of the liquid agent of this invention in the said range, a pH adjuster can also be mix | blended as needed. Examples of the pH adjuster include organic acids such as citric acid, malic acid, fumaric acid, tartaric acid, lactic acid and succinic acid and salts thereof, inorganic acids such as phosphoric acid and hydrochloric acid, inorganic bases such as sodium hydroxide, and the like. .
本発明の内服液剤にはその他の成分として、甘味料、酸味料、増粘安定剤、酸化防止剤、着色剤、香料、矯味剤、保存料、調味料、苦味料、強化剤、可溶化剤、乳化剤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ができる。 Other ingredients for the internal use liquid preparation of the present invention include sweeteners, acidulants, thickening stabilizers, antioxidants, coloring agents, flavorings, flavoring agents, preservatives, seasonings, bitterings, fortifiers, solubilizers. Additives such as emulsifiers can be appropriately blended within a range not impairing the effects of the present invention.
本発明の内服液剤は、常法により調製することができ、その方法は特に限定されるものではない。通常、各成分をとり適量の精製水で溶解した後、ｐＨを調整し、残りの精製水を加えて容量調整し、必要に応じてろ過処理することにより得られる。 The internal liquid preparation of the present invention can be prepared by a conventional method, and the method is not particularly limited. Usually, after each component is taken and dissolved with an appropriate amount of purified water, the pH is adjusted, the remaining purified water is added to adjust the volume, and filtration is performed as necessary.
本発明の内服液剤は光照射による色変化が抑制されるため、透明のガラス瓶や、ポリエチレンテレフタレート、ポリアクリレート、ポリエチレンナフタレート、ポリカーボネート、ポリエチレン、ポリプロピレン、ポリイミド等のプラスチック製の非遮光容器等に充填、保存することができる。 The internal liquid of the present invention suppresses color change due to light irradiation, so it fills transparent glass bottles and non-light-shielding containers made of plastic such as polyethylene terephthalate, polyacrylate, polyethylene naphthalate, polycarbonate, polyethylene, polypropylene, polyimide, etc. Can be saved.
本発明の内服液剤は、医薬品の各種製剤に適用することができる。 The internal liquid preparation of the present invention can be applied to various pharmaceutical preparations.
以下に実施例、比較例及び試験例を挙げ、本発明をさらに詳しく説明する。 Hereinafter, the present invention will be described in more detail with reference to Examples, Comparative Examples and Test Examples.
実施例１
塩酸アンブロキソール６０ｍｇ、タートラジン０．０８３ｍｇ、ソルビトール７０％溶液４５００ｍｇ、クエン酸１５ｍｇ、安息香酸ナトリウム２０ｍｇを精製水に溶解し、精製水を加えて全量を１０ｍＬとし、透明のガラス瓶に充填しキャップをし、澄明な内服液剤を得た（表１）。Example 1
60 mg of ambroxol hydrochloride, 0.083 mg of tartrazine, 4500 mg of 70% sorbitol solution, 15 mg of citric acid, 20 mg of sodium benzoate are dissolved in purified water. Thus, a clear internal solution was obtained (Table 1).
以下の実施例２〜４、比較例１〜５も実施例１と同様に調製した。 The following Examples 2 to 4 and Comparative Examples 1 to 5 were also prepared in the same manner as Example 1.
試験例１（目視観察）
実施例１〜４、比較例１〜２の試験液を調製し、目視による観察を行った。調製後の時間ごとの沈殿析出の様子を表２に示す。Test example 1 (visual observation)
Test solutions of Examples 1 to 4 and Comparative Examples 1 to 2 were prepared and observed visually. Table 2 shows the state of precipitation after each preparation.
表２から明らかなように、タートラジンを配合した実施例１〜４は、色素としてサンセットイエローＦＣＦを配合した比較例１及びアルラレッドＡＣを配合した比較例２と比較して沈殿の析出は見られず、性状安定性は良好であった。この結果から塩酸アンブロキソール配合内服液剤にタートラジンの配合が可能であることが明らかとなった。 As is clear from Table 2, in Examples 1 to 4 in which tartrazine was blended, precipitation of precipitates was observed as compared with Comparative Example 1 in which Sunset Yellow FCF was blended as a pigment and Comparative Example 2 in which Alla Red AC was blended. The property stability was good. From this result, it became clear that tartrazine can be added to the internal use solution containing ambroxol hydrochloride.
試験例２（光安定性試験）
実施例１〜４、比較例３〜５で得た試験液をＤ６５光源下で３０００Ｌｕｘ×６００時間曝光させた。これらの試験液の色を目視で観察した。結果を表３に示す。Test example 2 (light stability test)
The test solutions obtained in Examples 1 to 4 and Comparative Examples 3 to 5 were exposed to 3000 Lux × 600 hours under a D65 light source. The colors of these test solutions were visually observed. The results are shown in Table 3.
表３から、実施例１〜４は光経変後（Ｄ６５光源下３０００Ｌｕｘ×６００時間曝光後）も黄色の範疇であり、比較例３〜５と比較しても色の変化も小さかった。この結果からタートラジンを配合することで液剤の色変化を抑制できることが明らかとなった。 From Table 3, Examples 1 to 4 were in the yellow category even after phototransformation (after exposure to 3000 Lux × 600 hours under a D65 light source), and the color change was small even when compared with Comparative Examples 3 to 5. From this result, it became clear that the color change of the liquid agent can be suppressed by adding tartrazine.
本発明により、光照射による色の変化を抑制し、且つ色素沈殿が生じない安定な塩酸アンブロキソール含有内服液剤を提供することが可能となった。 According to the present invention, it has become possible to provide a stable ambroxol hydrochloride-containing internal liquid solution that suppresses color change due to light irradiation and does not cause pigment precipitation.
Claims (3)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2014028356 | 2014-02-18 | ||
| JP2014028356 | 2014-02-18 | ||
| PCT/JP2015/054203 WO2015125754A1 (en) | 2014-02-18 | 2015-02-17 | Internal liquid agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPWO2015125754A1 JPWO2015125754A1 (en) | 2017-03-30 |
| JP6372558B2 true JP6372558B2 (en) | 2018-08-15 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016504095A Active JP6372558B2 (en) | 2014-02-18 | 2015-02-17 | Oral solution |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JP6372558B2 (en) |
| PH (1) | PH12016501528A1 (en) |
| WO (1) | WO2015125754A1 (en) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3949184B2 (en) * | 1995-06-13 | 2007-07-25 | テイコクメディックス株式会社 | Ambroxol hydrochloride aqueous solution |
| JP2000007561A (en) * | 1998-06-18 | 2000-01-11 | Nissho Corp | Ambroxol hydrochloride aqueous solution preparation |
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2015
- 2015-02-17 JP JP2016504095A patent/JP6372558B2/en active Active
- 2015-02-17 WO PCT/JP2015/054203 patent/WO2015125754A1/en active Application Filing
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2016
- 2016-08-03 PH PH12016501528A patent/PH12016501528A1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PH12016501528B1 (en) | 2017-02-06 |
| JPWO2015125754A1 (en) | 2017-03-30 |
| WO2015125754A1 (en) | 2015-08-27 |
| PH12016501528A1 (en) | 2017-02-06 |
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