JP2022096991A - Pharmaceutical composition for external use - Google Patents
Pharmaceutical composition for external use Download PDFInfo
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- JP2022096991A JP2022096991A JP2020210317A JP2020210317A JP2022096991A JP 2022096991 A JP2022096991 A JP 2022096991A JP 2020210317 A JP2020210317 A JP 2020210317A JP 2020210317 A JP2020210317 A JP 2020210317A JP 2022096991 A JP2022096991 A JP 2022096991A
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- pharmaceutical composition
- external pharmaceutical
- isopropyl myristate
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- loxoprofen
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 56
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 claims abstract description 30
- 229960002373 loxoprofen Drugs 0.000 claims abstract description 30
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims abstract description 24
- 150000003839 salts Chemical class 0.000 claims abstract description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 15
- BAZQYVYVKYOAGO-UHFFFAOYSA-M loxoprofen sodium hydrate Chemical compound O.O.[Na+].C1=CC(C(C([O-])=O)C)=CC=C1CC1C(=O)CCC1 BAZQYVYVKYOAGO-UHFFFAOYSA-M 0.000 claims abstract 3
- 239000006185 dispersion Substances 0.000 abstract description 15
- YMBXTVYHTMGZDW-UHFFFAOYSA-N loxoprofen Chemical compound C1=CC(C(C(O)=O)C)=CC=C1CC1C(=O)CCC1 YMBXTVYHTMGZDW-UHFFFAOYSA-N 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- 239000000725 suspension Substances 0.000 description 16
- 239000003921 oil Substances 0.000 description 12
- 235000019198 oils Nutrition 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- 239000000203 mixture Substances 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000000654 additive Substances 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- -1 alkali metal salts Chemical class 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- TWJNQYPJQDRXPH-UHFFFAOYSA-N 2-cyanobenzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1C#N TWJNQYPJQDRXPH-UHFFFAOYSA-N 0.000 description 1
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 235000021360 Myristic acid Nutrition 0.000 description 1
- TUNFSRHWOTWDNC-UHFFFAOYSA-N Myristic acid Natural products CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000003908 antipruritic agent Substances 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 230000003631 expected effect Effects 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
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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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- 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
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
本発明は、ロキソプロフェン及び／又はその塩と、ミリスチン酸イソプロピルと、水とを含み、分散安定性が向上している外用医薬組成物に関する。 The present invention relates to an external pharmaceutical composition containing loxoprofen and / or a salt thereof, isopropyl myristate, and water, and having improved dispersion stability.
ロキソプロフェン及び／又はその塩は、解熱、鎮痛、及び消炎作用を有している非ステロイド性消炎鎮痛剤であり、外用医薬組成物に使用されている。一方、外用医薬組成物に液状油を配合することにより使用感を向上できることが知られている。そこで、従来、ロキソプロフェン及び／又はその塩と液状油を含む外用医薬組成物の処方について、種々報告されている。例えば、特許文献１には、ロキソプロフェン及び／又はその塩と、トコフェロール酢酸エステルと、液状油と、水とを含む外用医薬組成物が、優れた経皮浸透性を備え得ることが記載されている。 Loxoprofen and / or a salt thereof is a non-steroidal anti-inflammatory drug having antipyretic, analgesic, and anti-inflammatory effects, and is used in an external pharmaceutical composition. On the other hand, it is known that a feeling of use can be improved by blending a liquid oil with a pharmaceutical composition for external use. Therefore, various formulations of external pharmaceutical compositions containing loxoprofen and / or a salt thereof and a liquid oil have been conventionally reported. For example, Patent Document 1 describes that an external pharmaceutical composition containing loxoprofen and / or a salt thereof, tocopherol acetate, a liquid oil, and water can have excellent percutaneous permeability. ..
また、液状油の中でも、ミリスチン酸イソプロピルは、エリモント作用、ソフトでさっぱりした感触の付与等の点で優れており、外用医薬組成物にミリスチン酸イソプロピルを配合することよって良好な使用感を付与できることが知られている。そこで、ロキソプロフェン及び／又はその塩を含む外用医薬組成物において、使用感の向上等を図るべく、更にミリスチン酸イソプロピルを配合した製剤処方の開発が望まれている。 In addition, among liquid oils, isopropyl myristate is excellent in terms of elimont action, soft and refreshing feel, etc., and by blending isopropyl myristate in an external pharmaceutical composition, a good usability can be imparted. It has been known. Therefore, it is desired to develop a pharmaceutical composition containing isopropyl myristate in order to improve the usability in an external pharmaceutical composition containing loxoprofen and / or a salt thereof.
本発明者は、ロキソプロフェン及び／又はその塩と、ミリスチン酸イソプロピルと、水とを含む外用医薬組成物を開発すべく鋭意検討を行ったところ、当該外用医薬組成物ではミリスチン酸イソプロピルの分散安定性（分散された状態を安定に維持する特性）が低く、均一な懸濁状態を形成できないという課題を知得した。 The present inventor has made diligent studies to develop an external pharmaceutical composition containing loxoprofen and / or a salt thereof, isopropyl myristate, and water. In the external pharmaceutical composition, the dispersion stability of isopropyl myristate is stable. I learned that the (characteristic of maintaining a stable dispersed state) is low and that a uniform suspension state cannot be formed.
そこで、本発明の目的は、ロキソプロフェン及び／又はその塩と、ミリスチン酸イソプロピルと、水とを含み、分散安定性が向上している外用医薬組成物を提供することである。 Therefore, an object of the present invention is to provide an external pharmaceutical composition containing loxoprofen and / or a salt thereof, isopropyl myristate, and water, and having improved dispersion stability.
本発明者は、前記課題を解決すべく鋭意検討を行ったところ、ロキソプロフェン及び／又はその塩と、ミリスチン酸イソプロピルと、水とを含む外用医薬組成物に、Ｎ－メチル－２－ピロリドンを配合することによって、分散安定性が向上し、均一な懸濁状態を形成できることを見出した。本発明は、かかる知見に基づいて、更に検討を重ねることにより完成したものである。 As a result of diligent studies to solve the above problems, the present inventor has added N-methyl-2-pyrrolidone to an external pharmaceutical composition containing loxoprofen and / or a salt thereof, isopropyl myristate, and water. By doing so, it was found that the dispersion stability was improved and a uniform suspension state could be formed. The present invention has been completed by further studies based on such findings.
即ち、本発明は、下記に掲げる態様の発明を提供する。
項１． (A)ロキソプロフェン及び／又はその塩、(B)ミリスチン酸イソプロピル、(C)Ｎ－メチル－２－ピロリドン、並びに(D)水を含有する、外用医薬組成物。
項２． 前記(C)成分の含有量が２～１５重量％である、項１に記載の外用医薬組成物。
That is, the present invention provides the inventions of the following aspects.
Item 1. An external pharmaceutical composition comprising (A) loxoprofen and / or a salt thereof, (B) isopropyl myristate, (C) N-methyl-2-pyrrolidone, and (D) water.
Item 2. Item 2. The external pharmaceutical composition according to Item 1, wherein the content of the component (C) is 2 to 15% by weight.
本発明によれば、ロキソプロフェン及び／又はその塩と、ミリスチン酸イソプロピルと、水とを含む外用医薬組成物において、ミリスチン酸イソプロピルの分散安定性が向上しており、均一な懸濁状態を形成させることができる。 According to the present invention, in an external pharmaceutical composition containing loxoprofen and / or a salt thereof, isopropyl myristate, and water, the dispersion stability of isopropyl myristate is improved and a uniform suspension state is formed. be able to.
１．外用医薬組成物
本発明の外用医薬組成物は、(A)ロキソプロフェン及び／又はその塩、(B)ミリスチン酸イソプロピル、(C)Ｎ－メチル－２－ピロリドン、並びに(D)水を含有することを特徴とする。以下、本発明の外用医薬組成物について詳述する。
1. 1. External Pharmaceutical Composition The external pharmaceutical composition of the present invention contains (A) loxoprofen and / or a salt thereof, (B) isopropyl myristate, (C) N-methyl-2-pyrrolidone, and (D) water. It is characterized by. Hereinafter, the external pharmaceutical composition of the present invention will be described in detail.
［(A)ロキソプロフェン及び／又はその塩］
本発明の外用医薬組成物は、ロキソプロフェン及び／又はその塩（(A)成分と表記することもある）を含有する。ロキソプロフェンは、２－［パラ－（２－オキソシクロペンチルメチル）フェニル］プロピオン酸とも称される非ステロイド性消炎鎮痛薬である。
[(A) Loxoprofen and / or its salt]
The external pharmaceutical composition of the present invention contains loxoprofen and / or a salt thereof (sometimes referred to as component (A)). Loxoprofen is a non-steroidal anti-inflammatory drug, also called 2- [para- (2-oxocyclopentylmethyl) phenyl] propionic acid.
ロキソプロフェンの塩としては、薬学上許容されることを限度として特に制限されないが、例えばナトリウム塩、カリウム塩等のアルカリ金属塩；カルシウム塩等のアルカリ土類金属塩等が挙げられる。また、ロキソプロフェンの塩は、水和物であってもよい。 The salt of loxoprofen is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include alkali metal salts such as sodium salt and potassium salt; and alkaline earth metal salts such as calcium salt. Further, the salt of loxoprofen may be a hydrate.
(A)成分として、ロキソプロフェン及び／又はその塩の中から１種を選択して単独で使用してもよく、また２種以上を組み合わせて使用してもよい。(A)成分の中でも、好ましくはロキソプロフェンの塩、より好ましくはロキソプロフェンナトリウム、更に好ましくはロキソプロフェンナトリウム水和物が挙げられる。 As the component (A), one of loxoprofen and / or a salt thereof may be selected and used alone, or two or more thereof may be used in combination. Among the components (A), a salt of loxoprofen is preferable, loxoprofen sodium is more preferable, and loxoprofen sodium hydrate is more preferable.
本発明の外用医薬組成物における(A)成分の含有量は、備えさせるべき薬効等に応じて適宜設定すればよいが、例えば０．１～１０重量％、好ましくは０．５～３重量％、より好ましくは０．５～２重量％が挙げられる。 The content of the component (A) in the external pharmaceutical composition of the present invention may be appropriately set according to the medicinal effect to be provided, for example, 0.1 to 10% by weight, preferably 0.5 to 3% by weight. , More preferably 0.5 to 2% by weight.
［(B)ミリスチン酸イソプロピル］
本発明の外用医薬組成物は、ミリスチン酸イソプロピル（(B)成分と表記することもある）を含有する。ミリスチン酸イソプロピルとは、ミリスチン酸とイソプロピルアルコールがエステル結合している脂肪酸アルキルエステルである。
[(B) Isopropyl myristate]
The external pharmaceutical composition of the present invention contains isopropyl myristate (sometimes referred to as component (B)). Isopropyl myristate is a fatty acid alkyl ester in which myristic acid and isopropyl alcohol are ester-bonded.
本発明の外用医薬組成物における(B)成分の含有量は、付与すべく使用感等に応じて適宜設定すればよいが、例えば０．１～３０重量％、好ましくは０．５～２０重量％、より好ましくは１～１０重量％が挙げられる。 The content of the component (B) in the external pharmaceutical composition of the present invention may be appropriately set according to the feeling of use and the like, and is, for example, 0.1 to 30% by weight, preferably 0.5 to 20% by weight. %, More preferably 1-10% by weight.
本発明の外用医薬組成物において、(A)成分に対する(B)成分の比率については、これらの成分の各含有量に応じて定まるが、例えば、(A)成分１重量部当たり、(B)成分が０．０１～１０００重量部、好ましくは０．１～１００重量部、より好ましくは０．５～２０重量部が挙げられる。 In the external pharmaceutical composition of the present invention, the ratio of the component (B) to the component (A) is determined according to the content of each of these components. The components are 0.01 to 1000 parts by weight, preferably 0.1 to 100 parts by weight, and more preferably 0.5 to 20 parts by weight.
［(C)Ｎ－メチル－２－ピロリドン］
本発明の外用医薬組成物は、前記成分に加えて、Ｎ－メチル－２－ピロリドン（(C)成分と表記することもある）を含有する。本発明の外用医薬組成物では、ロキソプロフェン及び／又はその塩とミリスチン酸イソプロピルと共に、Ｎ－メチル－２－ピロリドンを含むことにより、ミリスチン酸イソプロピルの分散安定性が向上し、均一な懸濁状態を形成させることが可能になる。Ｎ－メチル－２－ピロリドンとは、２－ピロリドンの窒素原子にメチル基が置換されている化合物である。
[(C) N-methyl-2-pyrrolidone]
The external pharmaceutical composition of the present invention contains N-methyl-2-pyrrolidone (sometimes referred to as component (C)) in addition to the above-mentioned components. In the external pharmaceutical composition of the present invention, the dispersion stability of isopropyl myristate is improved and a uniform suspension state is maintained by containing N-methyl-2-pyrrolidone together with loxoprofen and / or a salt thereof and isopropyl myristate. It becomes possible to form. N-methyl-2-pyrrolidone is a compound in which a methyl group is substituted on the nitrogen atom of 2-pyrrolidone.
本発明の外用医薬組成物における(C)成分の含有量としては、例えば、０．１～２０重量％が挙げられる。ミリスチン酸イソプロピルの分散安定性をより一層向上させるという観点から、好ましくは１～１５重量％、本発明の外用医薬組成物における(C)成分の含有量として、より好ましくは２～１５重量％、更に好ましくは５～１５重量％が挙げられる。 Examples of the content of the component (C) in the external pharmaceutical composition of the present invention include 0.1 to 20% by weight. From the viewpoint of further improving the dispersion stability of isopropyl myristate, the content of the component (C) in the external pharmaceutical composition of the present invention is preferably 1 to 15% by weight, more preferably 2 to 15% by weight. More preferably, 5 to 15% by weight is mentioned.
本発明の外用医薬組成物において、(A)成分に対する(C)成分の比率については、これらの成分の各含有量に応じて定まるが、例えば、(A)成分１重量部当たり、(C)成分が０．０１～１０００重量部、好ましくは０．１～１００重量部、より好ましくは１～２０重量部、更に好ましくは５～１５重量部が挙げられる。 In the external pharmaceutical composition of the present invention, the ratio of the component (C) to the component (A) is determined according to the content of each of these components. For example, (C) per part by weight of the component (A). The components are 0.01 to 1000 parts by weight, preferably 0.1 to 100 parts by weight, more preferably 1 to 20 parts by weight, still more preferably 5 to 15 parts by weight.
［(D)水］
本発明の外用医薬組成物には、基剤として水が含まれる。本発明の外用医薬組成物における水の含有量は、配合する他の成分を除いた残部であればよいが、例えば、５～９９重量％、好ましくは１０～９２重量％が挙げられる。
[(D) Water]
The external pharmaceutical composition of the present invention contains water as a base. The content of water in the external pharmaceutical composition of the present invention may be the balance excluding other components to be blended, and examples thereof include 5 to 99% by weight, preferably 10 to 92% by weight.
［１価低級アルコール］
本発明の外用医薬組成物は、更に１価低級アルコールを含んでいてもよい。本発明において、１価低級アルコールとは炭素数１～５の１価アルコールを指す。
[Monohydric lower alcohol]
The external pharmaceutical composition of the present invention may further contain a monohydric lower alcohol. In the present invention, the monohydric lower alcohol refers to a monohydric alcohol having 1 to 5 carbon atoms.
１価低級アルコールの種類については、薬学的に許容されることを限度として特に制限されないが、例えば、エタノール、ｎ－プロパノール、イソプロパノール等が挙げられる。これらの１価低級アルコールは、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。 The type of monohydric lower alcohol is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include ethanol, n-propanol, and isopropanol. These monohydric lower alcohols may be used alone or in combination of two or more.
これらの１価低級アルコールの中でも、好ましくはエタノール、イソプロパノール、より好ましくはエタノールが挙げられる。 Among these monohydric lower alcohols, ethanol, isopropanol, and more preferably ethanol are preferable.
本発明の外用医薬組成物に１価低級アルコールを含有させる場合、その含有量については、特に制限されないが、例えば、０．１～８０重量％、好ましくは１～７５重量％が挙げられる。 When the monohydric lower alcohol is contained in the external pharmaceutical composition of the present invention, the content thereof is not particularly limited, and examples thereof include 0.1 to 80% by weight, preferably 1 to 75% by weight.
[その他の成分]
本発明の外用医薬組成物は、前述する成分の他に、必要に応じて、通常使用される他の添加剤が含まれていてもよい。このような添加剤としては、例えば、界面活性剤、植物油、動物油、鉱物油、脂肪酸アルキルエステル（(B)成分以外）、脂肪酸、高級アルコール、ｐＨ調節剤、緩衝剤、可溶化剤、防腐剤、保存剤、酸化防止剤、安定化剤、香料、着色料等が挙げられる。本発明の外用医薬組成物において、これらの添加剤を含有させる場合、その含有量については、使用する添加剤の種類等に応じて適宜設定すればよい。
[Other ingredients]
In addition to the above-mentioned components, the external pharmaceutical composition of the present invention may contain other commonly used additives, if necessary. Examples of such additives include surfactants, vegetable oils, animal oils, mineral oils, fatty acid alkyl esters (other than component (B)), fatty acids, higher alcohols, pH adjusters, buffers, solubilizers, and preservatives. , Preservatives, antioxidants, stabilizers, fragrances, colorants and the like. When these additives are contained in the external pharmaceutical composition of the present invention, the content thereof may be appropriately set according to the type of the additive to be used and the like.
また、本発明の外用医薬組成物は、前述する成分の他に、薬理成分が含まれていてもよい。このような薬理成分としては、例えば、抗ヒスタミン剤、保湿剤、殺菌剤、抗菌剤、鎮痒剤、皮膚保護剤、血行促進成分、ビタミン類等が挙げられる。これらの薬理成分は、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。また、本発明の外用医薬組成物において、これらの薬理成分を含有させる場合、その濃度については、使用する薬理成分の種類、期待する効果等に応じて適宜設定すればよい。 Further, the external pharmaceutical composition of the present invention may contain a pharmacological component in addition to the above-mentioned components. Examples of such pharmacological components include antihistamines, moisturizers, bactericidal agents, antibacterial agents, antipruritic agents, skin protectants, blood circulation promoting components, vitamins and the like. These pharmacological components may be used alone or in combination of two or more. In addition, when these pharmacological components are contained in the external pharmaceutical composition of the present invention, the concentration thereof may be appropriately set according to the type of the pharmacological component used, the expected effect, and the like.
［製剤形態］
本発明の外用医薬組成物の製剤形態については、経皮投与可能であることを限度として特に制限されず、例えば、液剤（懸濁液）、フォーム剤、軟膏剤、クリーム剤、ゲル剤等が挙げられる。これらの中でも、好ましくは液剤が挙げられる。これらの製剤形態への調製は、第十七改正日本薬局方 製剤総則等に記載の公知の方法に従って、製剤形態に応じた添加剤を用いて製剤化することにより行うことができる。
[Pharmaceutical form]
The pharmaceutical form of the external pharmaceutical composition of the present invention is not particularly limited as long as it can be administered transdermally, and examples thereof include liquids (suspensions), foams, ointments, creams, and gels. Can be mentioned. Among these, a liquid agent is preferable. Preparation of these formulations can be carried out by formulating them with additives according to the formulation form according to the known method described in the 17th revised Japanese Pharmacopoeia General Regulations for Formulations.
以下に実施例を示して本発明をより具体的に説明するが、本発明はこれらに限定されるものではない。 Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.
試験例１
表１に示す組成の外用医薬組成物（懸濁液）を以下の方法で調製した。具体的には、ロキソプロフェンナトリウム水和物、水及びエタノールを所定量混合して溶解させた後に、ミリスチン酸イソプロピルを混合しながら徐々に添加し、最後にＮ－メチル－２－ピロリドン、プロピレングリコール又はグリセリンを所定量添加して、均一になるまで撹拌することにより、外用医薬組成物（懸濁液）を調製した。
Test Example 1
An external pharmaceutical composition (suspension) having the composition shown in Table 1 was prepared by the following method. Specifically, loxoprofen sodium hydrate, water and ethanol are mixed and dissolved in a predetermined amount, and then isopropyl myristate is gradually added while mixing, and finally N-methyl-2-pyrrolidone, propylene glycol or An external pharmaceutical composition (suspension) was prepared by adding a predetermined amount of glycerin and stirring until uniform.
調製した各外用医薬組成物を室温で１０分間静置した後に外観を観察し、「油分（ミリスチン酸イソプロピル）が著しく分離しており、均一な懸濁液を形成していない」を１点、「油分（ミリスチン酸イソプロピル）の分離が全く認められず、均一な懸濁液を形成している」を１０点として、分散状態の程度に応じて１～１０点の１０段階で分散安定性を評点化した。なお、参考のために、前記評点において１点及び１０点の状態の外用医薬組成物の外観を撮影した写真を図１に示す。なお、前記評点において、５点以上の場合には、実用化する上で許容できる分散安定性を有していると判定できる。 After allowing each of the prepared external pharmaceutical compositions to stand at room temperature for 10 minutes, the appearance was observed, and one point was "the oil (isopropyl myristate) was significantly separated and a uniform suspension was not formed". With 10 points as "no separation of oil (isopropyl myristate) is observed and a uniform suspension is formed", dispersion stability is determined in 10 steps from 1 to 10 points depending on the degree of dispersion. Scored. For reference, FIG. 1 shows photographs of the appearance of the external pharmaceutical composition in the state of 1 point and 10 points in the above-mentioned scores. If the score is 5 or more, it can be determined that the score has an acceptable dispersion stability for practical use.
結果を表１に示す。また、図１に実施例３及び比較例１の外用医薬組成物の外観を撮影した写真を示す。ミリスチン酸イソプロピルのみを添加した外用医薬組成物では、油分（ミリスチン酸イソプロピル）が著しく上層に分離しており、均一な懸濁液を形成できていなかった（比較例１）。ロキソプロフェンナトリウム水和物及びミリスチン酸イソプロピルのみを添加した外用医薬組成物では、比較例１よりは分散状態が向上したが油分の多くが分離して上層に分布しており、均一な懸濁液を形成できなかった（比較例２）。また、ロキソプロフェンナトリウム水和物及びミリスチン酸イソプロピルと共に、分散剤として使用されているプロピレングリコール又はグリセリンを含んでいても、油分の多くが分離して上層に分布しており、均一な懸濁液を形成できなかった（比較例３及び４）。これに対して、ロキソプロフェンナトリウム水和物及びミリスチン酸イソプロピルと共に、Ｎ－メチル－２－ピロリドンを添加した外用医薬組成物では、油分の分離が認められず、均一な懸濁液を形成できていた（実施例１～７）。特に、Ｎ－メチル－２－ピロリドンの含有量が２重量％以上、特に５重量％以上の場合には、格段に優れた分散安定性が認められた（実施例２～７）。なお、実施例３においてロキソプロフェンナトリウム水和物を未配合に変更した外用医薬組成物では、油分の多くが分離して上層に分布しており、均一な懸濁液を形成できなかった（比較例５）。よって、ロキソプロフェンナトリウム水和物もミリスチン酸イソプロピルの分散安定性を向上することが認められた。また、実施例６及び７においてエタノールをイソプロパノールに変更した外用医薬組成物でも、実施例６及び７と同様に油分の分離が認められず、均一な懸濁液を形成できていた。 The results are shown in Table 1. Further, FIG. 1 shows photographs of the appearances of the external pharmaceutical compositions of Example 3 and Comparative Example 1. In the external pharmaceutical composition to which only isopropyl myristate was added, the oil (isopropyl myristate) was remarkably separated in the upper layer, and a uniform suspension could not be formed (Comparative Example 1). In the external pharmaceutical composition to which only loxoprofen sodium hydrate and isopropyl myristate were added, the dispersed state was improved as compared with Comparative Example 1, but most of the oil content was separated and distributed in the upper layer, and a uniform suspension was obtained. It could not be formed (Comparative Example 2). Further, even if propylene glycol or glycerin used as a dispersant is contained together with loxoprofen sodium hydrate and isopropyl myristate, most of the oil content is separated and distributed in the upper layer, so that a uniform suspension can be obtained. It could not be formed (Comparative Examples 3 and 4). On the other hand, in the external pharmaceutical composition to which N-methyl-2-pyrrolidone was added together with loxoprofen sodium hydrate and isopropyl myristate, separation of oil content was not observed, and a uniform suspension could be formed. (Examples 1 to 7). In particular, when the content of N-methyl-2-pyrrolidone was 2% by weight or more, particularly 5% by weight or more, remarkably excellent dispersion stability was observed (Examples 2 to 7). In the external pharmaceutical composition in which loxoprofen sodium hydrate was changed to unblended in Example 3, most of the oil content was separated and distributed in the upper layer, and a uniform suspension could not be formed (Comparative Example). 5). Therefore, it was found that loxoprofen sodium hydrate also improved the dispersion stability of isopropyl myristate. Further, even in the external pharmaceutical compositions in which ethanol was changed to isopropanol in Examples 6 and 7, separation of oil content was not observed as in Examples 6 and 7, and a uniform suspension could be formed.
処方例
表２に示す組成の外用医薬組成物（懸濁液）を試験例１と同様の方法で調製し、試験例１と同様の方法で外観を観察したところ、処方例１～８いずれの外用医薬組成物においても分散安定性が認められた。
Formulation Example An external pharmaceutical composition (suspension) having the composition shown in Table 2 was prepared by the same method as in Test Example 1, and the appearance was observed by the same method as in Test Example 1. As a result, any of Formulation Examples 1 to 8 was observed. Dispersion stability was also observed in the external pharmaceutical composition.
Claims (2)
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| TW110142463A TW202228668A (en) | 2020-12-18 | 2021-11-16 | Pharmaceutical composition for external use |
| PCT/JP2021/044977 WO2022131082A1 (en) | 2020-12-18 | 2021-12-07 | Pharmaceutical composition for external use |
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| JPH10120560A (en) * | 1996-08-26 | 1998-05-12 | Sankyo Co Ltd | Loxoprofen-containing preparation for external use |
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| JP6516083B2 (en) * | 2013-06-05 | 2019-05-22 | 国立大学法人九州大学 | Percutaneous absorption substrate |
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| JP7186025B2 (en) * | 2018-06-27 | 2022-12-08 | 小林製薬株式会社 | External pharmaceutical composition |
| JP7164976B2 (en) * | 2018-06-27 | 2022-11-02 | 小林製薬株式会社 | External pharmaceutical composition |
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