JP2019119686A - External preparation - Google Patents

Abstract

To provide a preparation in which an external agent containing menthol, a C1-4 alcohol, and water is packed in a neck-bent container, and precipitation of menthol is suppressed at the lower side of a neck part.SOLUTION: An external preparation contains (a) an external agent and (b) a container that stores the external agent (a). The external agent (a) contains: loxoprofen and/or a pharmaceutically acceptable salt thereof; menthol; a C1-4 alcohol; and water, and the container (b) has a trunk, and a neck part with a mouth part, in which the neck part is inclined relative to the vertical central axis of the trunk.SELECTED DRAWING: None

Description

  The present invention relates to external preparations.

  Conventionally, an external preparation containing menthol as a cooling component is used as an external preparation applied to shoulder stiffness and the like (Patent Document 1).

JP, 2011-074032, A

  The inventor of the present invention is a container comprising a body and a neck having a mouth, wherein the neck is inclined with respect to the longitudinal central axis of the body, the external preparation is stored in the body at the time of storage, Menthol is compounded as an active ingredient in a container (sometimes referred to herein as a "bent container") capable of discharging an external preparation from the mouth by tilting and applying it to the affected area, and these are incorporated into the lower alcohol It was conceived to use an external preparation mixed with a solvent containing water and water.

  However, the inventor found the problem that menthol deposits on the lower side of the neck when the external preparation thus obtained is stored after being used as described above. The present invention provides a preparation in which a menthol, an alcohol having 1 to 4 carbon atoms, and an external preparation containing water are filled in a necked container, and the preparation in which precipitation of menthol on the lower side of the neck is suppressed. To be a task.

  The inventors of the present invention conducted intensive studies to solve the above problems, and found that, in a composition containing menthol, an alcohol having 1 to 4 carbon atoms, and water, an external preparation obtained by incorporating loxoprofen is used. It has been found that the filling of the bent container suppresses the deposition of menthol below the neck, even when stored after use. The present invention has been completed by further investigation based on such findings, and includes the following aspects.

Item 1.
An external preparation comprising (a) an external preparation, and (b) a container for containing the external preparation (a),
Said external preparation (a) is:
At least one selected from the group consisting of loxoprofen and / or a pharmaceutically acceptable salt thereof;
menthol;
It is an external preparation containing an alcohol having 1 to 4 carbon atoms; and water.
The external preparation, wherein the container (b) comprises a body and a neck having a mouth, and the neck is inclined with respect to a central longitudinal axis of the body.
Item 2.
The external preparation preparation according to item 1, wherein the pharmaceutically acceptable salt of loxoprofen is loxoprofen sodium hydrate.
Item 3.
The external preparation according to item 1 or 2, wherein the external preparation further contains a polyhydric alcohol.
Item 4.
The external preparation as described in any one of Items 1 to 3, wherein the container is made of polyethylene or polypropylene.
Item 5.
The external preparation according to any one of Items 1 to 4, wherein the length of the lower side of the neck is 0.5 to 10 cm.

  According to the present invention, the external preparation containing menthol, an alcohol having 1 to 4 carbon atoms, and water is a preparation for external use filled in a necked container, and the precipitation of menthol on the lower side of the neck is suppressed An external preparation can be provided.

It is a schematic diagram of the necked container used by this invention. It is a schematic diagram of the external preparation of this invention at the time of storage. It is a schematic diagram of the external preparation of this invention at the time of use. It is a photograph which shows the evaluation result of comparative example 1 and Example 1 and 2. It is a photograph which shows the evaluation result of comparative example 2 and example 3.

1. External preparation and its preparation method The external preparation used in the present invention is:
At least one selected from the group consisting of loxoprofen and / or a pharmaceutically acceptable salt thereof;
menthol;
It contains an alcohol having 1 to 4 carbon atoms; and water.

1.1. Loxoprofen and its pharmaceutically acceptable salt (loxoprofen)
By containing the loxoprofen, the external preparation used in the present invention is one in which the deposition of menthol at the neck of the necked container is suppressed.

  Loxoprofen (2- [4- (2-oxocyclopentylmethyl) phenyl] propionic acid) is a non-steroidal non-steroidal antipyretic analgesic / antiinflammatory agent (NSAID) having antipyretic, analgesic and anti-inflammatory activity.

  In the present invention, in addition to loxoprofen itself, pharmaceutically acceptable salts thereof can also be used. Such salts also include solvates of loxoprofen or a pharmaceutically acceptable salt thereof with water, alcohol and the like. These are known compounds and can be produced by known methods, and commercially available ones can also be used.

  In the present invention, loxoprofen is preferably loxoprofen sodium hydrate.

  The external preparation used in the present invention may contain one kind of loxoprofen alone, or may contain plural kinds in combination.

  The content of loxoprofen can be appropriately set in consideration of the effects of the present invention and the antipyretic, analgesic and anti-inflammatory actions, and is not particularly limited. The content of loxoprofen can be, for example, 0.1 to 20% by mass in terms of loxoprofen sodium anhydride in total based on the total external preparation used in the present invention. A sufficient antipyretic, analgesic and antiphlogistic action can be obtained when the content of loxoprofen is at least 0.1% by mass in terms of loxoprofen sodium anhydride in total amount with respect to the whole external preparation. In this aspect, the content of loxoprofen is preferably 0.2% by mass or more, more preferably 0.5% by mass or more, in terms of the total amount of loxoprofen sodium anhydride based on the whole external preparation. And 1% by mass or more. In addition, in view of the minimum amount that can provide sufficient antipyretic, analgesic and anti-inflammatory effects, the content of loxoprofen is preferably 15 mass in total of loxoprofen sodium anhydride in total with respect to the whole external preparation used in the present invention % Or less, more preferably 10% by mass or less, still more preferably 5% by mass or less.

1.2. Menthol The external preparation used in the present invention has a refreshing feeling by containing menthol.

  The menthol contained in the external preparation used in the present invention is not particularly limited, and may be any of l-menthol, d-menthol and dl-menthol, and may be one or more of these.

  The content of menthol can be appropriately set in consideration of the effect of the present invention that precipitation at the neck is suppressed and the effect as a cooling agent, and is not particularly limited. The content of menthol can be, for example, 0.1 to 20% by mass in total with respect to the entire external preparation used in the present invention. From the viewpoint of the effect of suppressing white turbidity, the content of menthol is preferably 1% by mass or more, more preferably 2% by mass or more in the total amount with respect to the entire external preparation. In addition, in view of the minimum amount at which a sufficient cooling effect can be obtained, the content of menthol is preferably 10% by mass or less, more preferably 6% by mass or less, still more preferably 3% by mass with respect to the entire external preparation. % Or less.

1.3. C1-C4 alcohol (lower alcohol)
The external preparation used in the present invention contains a lower alcohol. The lower alcohol is not particularly limited, and can be widely used as long as it functions as an effective base for the above components.

  Specific examples of lower alcohols include methanol, ethanol, propyl alcohol and isopropyl alcohol, with ethanol being preferred.

  The external preparation preferably contains 40 to 90% by mass of the lower alcohol based on the whole external preparation. Specifically, when the external preparation contains ethanol as a lower alcohol, it is preferably 50% by mass or more, more preferably 50 to 90% by mass, still more preferably 60 to 90% by mass, and even more preferably 65% by mass. 80 mass% is included. In addition, when the external preparation contains isopropanol as the lower alcohol, isopropanol is preferably 40% by mass or more, more preferably 40 to 90% by mass, still more preferably 50 to 90% by mass, still more preferably 50 to 80%. % Included.

1.4. Polyhydric alcohol The external preparation used in the present invention may further contain a polyhydric alcohol.

  As the polyhydric alcohol, glycols and the like can be used. The glycols are not particularly limited, and examples thereof include glycerin, propylene glycol, 1,3-butylene glycol, octanediol, ethylene glycol, polyethylene glycol, D-sorbitol and the like. Glycerin, propylene glycol and 1,3-butylene glycol are preferred.

  A polyhydric alcohol may be used individually by 1 type, and may be used in combination of multiple types.

  The external preparation preferably contains the polyhydric alcohol in a total amount of 1 to 30% by mass, more preferably 2 to 20% by mass, and still more preferably 3 to 15% by mass, based on the entire external preparation.

1.5. In addition to the above components, a blood circulation promoting component can be added to the other component external preparation, as long as the effects of the present invention are not impaired.

  Examples of the blood circulation promoting component include capsaicinoid and the like.

  As a capsaicinoid, N-acylanilylamide can be used.

  The acyl group in the N-acylanilylamide may be linear or branched. Moreover, it does not restrict | limit in particular about carbon number of the acyl group in N-acyl crocodyl arylamide, For example, 5-15, Preferably it can be 6-11 grade | etc.,.

  Specific examples of the N-acylanilylamide include nonanoic acid vanillylamide and capsaicins such as capsaicin, dihydrocapsaicin, nordihydrocapsaicin, homocapsaicin and homodihydrocapsaicin.

  In the present invention, the capsaicinoid may be a purified product, but a mixture containing other components besides capsaicinoid may be used. Specific examples of such a mixture containing capsaicinoid include capsicum extracts such as capsicum extract (capsicum extract), capsicum tincture and capsicum powder.

  The pepper extract is not particularly limited and can be widely used. As the red pepper extract, a single type of red pepper extract may be used, or a plurality of red pepper extracts may be used in combination. For example, as a chili pepper extract, an alcoholic extract of chili pepper can be used. As an alcohol extract of red pepper, for example, an ethanol extract of red pepper can be used.

  In the present invention, as capsaicinoids, one capsaicinoid may be used alone, or two or more may be used in combination.

  Among the capsaicinoids, pepper extract and / or nonanoic acid vanillylamide is preferable from the viewpoint that the effect of suppressing white turbidity in the composition is more easily obtained.

  Still other circulation promoting components include, for example, ester derivatives of nicotinic acid.

  As the ester derivative of nicotinic acid, the ester derivative of nicotinic acid is not particularly limited as long as it is pharmaceutically acceptable, and can be widely used. For example, nicotinic acid benzyl ester, nicotinic acid β-butoxyethyl ester, nicotinic acid methyl ester and the like can be mentioned. These ester derivatives of nicotinic acid may be used alone or in combination of two or more. Among ester derivatives of nicotinic acid, nicotinic acid benzyl ester is preferred.

  As another blood circulation promoting component, for example, tocopherols and the like can be mentioned.

  The tocopherols are not particularly limited, and can be widely used including derivatives. The type of tocopherol itself may be any of α-tocopherol, β-tocopherol, γ-tocopherol and δ-tocopherol, but α-tocopherol is preferred.

  The derivative of tocopherol is not particularly limited as far as it is pharmaceutically acceptable, and examples thereof include esters with carboxylic acids such as acetic acid, nicotinic acid and succinic acid, and diesters with phosphoric acid. Among these derivatives of tocopherol, an ester with a carboxylic acid is preferable, and tocopherol acetate (tocopherol acetate) is more preferable.

  The external preparation may contain tocopherols singly or in combination of two or more.

  In addition to the above components, an additional refreshing agent may be added to the external preparation, as long as the effects of the present invention are not impaired.

  As such a refreshing agent, d-camphor, dl-camphor, d-borneol, dl-borneol, mentane, menthyl lactate, geraniol, eucalyptus oil, terpene oil, bergamot oil, fennel oil, peppermint oil, pepper oil (peppermint), rose oil And cool mint and the like. These cooling agents may be used alone or in any combination of two or more.

  The refreshing agent contained in the external preparation is preferably d-borneol, dl-borneol, menthane, peppermint oil (peppermint) and coolmint.

  In addition to the above-mentioned components, a drug efficacy adjuvant may be added to the external preparation as long as the effects of the present invention are not impaired.

  Such drug adjuvants include anti-inflammatory agents and skin protecting agents such as glycyrrhetinic acid, dipotassium glycyrrhizinate, ammonium glycyrrhizinate, stearyl glycyrrhizinate; diphenylimidazole, diphenhydramine and pharmaceutically acceptable salts thereof, chlorphene maleate And antihistamines such as lamin; and herbal medicines such as arnica tincture, oat extract, Sanshish extract, horseradish extract, rhodox extract, veradonna extract, sweet potato extract, sikon extract, sansho extract and the like.

  In the external preparation, in addition to the above-mentioned components, additives used in common external preparations such as active ingredients, pH adjusters, preservatives, preservatives, antioxidants, stabilizers and the like which can be used in combination are appropriately blended. be able to.

1.6. Form and Production Method The external preparation is not particularly limited in its form, but is preferably a liquid preparation (including lotions and emulsions).

  The external preparation can be prepared according to a conventional method according to such a formulation form. For example, a method of dissolving or dispersing loxoprofen, menthol, and other components, if necessary, in a general-purpose base as described below including lower alcohol and water, and adjusting to a desired pH Can be mentioned.

  The pH is not limited as long as it has no adverse effect on the skin, and is usually adjusted to 3.5 to 8.5, preferably 4 to 8, and more preferably 4 to 7.5.

  For example, when the external preparation is prepared as a liquid preparation, it can be prepared by mixing loxoprofen, menthol and, if necessary, other components with a lower alcohol and a water-based base. The base may contain at least one selected from polyhydric alcohols, water and emulsifiers. As polyhydric alcohol, the above-mentioned thing etc. can be used.

  The emulsifier is not particularly limited, and examples thereof include nonionic surfactants such as sorbitan fatty acid ester, glycerin fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyl stearate, lauromacrogol and the like. An emulsifier may be used individually by 1 type, and may be used in combination of multiple types.

  The external preparation is preferably prepared as an external preparation in a form of application, and can be topically administered topically.

  Although the dose of the external preparation depends on the degree of the condition to be treated, the total applied dose per day of loxoprofen which is the active ingredient contained therein is 100 mg or less desirable.

  The external preparation is preferably a medicine. The external preparation which is the medicine of the present invention is an external antiphlogistic and analgesic agent, shoulder pain with stiff shoulder, joint pain, back pain, muscle pain, tendonitis (hand and wrist pain), elbow pain (tennis elbow etc.), bruises For pain such as pain, itching pain, fracture pain, neuralgia etc., it can be suitably used for the purpose of analgesia.

2. Neck-bent container In the present invention, the external preparation can be filled into a neck-bent container to obtain an external preparation (externally applied product). The necked container used in the present invention is a container comprising a body portion and a neck portion provided with a mouth portion, wherein the neck portion is inclined with respect to a longitudinal central axis of the body portion. Specifically, the necked container used in the present invention stores the external preparation in the barrel during storage (FIG. 2), and discharges the external preparation from the mouth by tilting the container at the time of use A necked container used for application to the affected area (Figure 3).

  The inclination angle of the neck with respect to the longitudinal central axis of the body is preferably 30 to 90 °, more preferably 40 to 90 °, still more preferably 50 to 90 °, and still more preferably 55 to 90 °. Generally, as the angle approaches 90 °, the external preparation remaining on the neck immediately after use becomes less likely to return to the trunk during storage, and menthol is more likely to precipitate. In addition, the angle of inclination of a neck points out the angle which the longitudinal direction central axis of a trunk | drum and the longitudinal direction central axis of a neck make (FIG. 1).

  The material of the necked container is not particularly limited and can be widely selected. As a material of the necked container, polyethylene or polypropylene is preferable.

  When the length of the lower side of the neck is longer, the external preparation remaining on the neck immediately after use is less likely to return to the trunk during storage, and menthol is more likely to precipitate (FIG. 1). In the external preparation according to the present invention, the deposition of menthol is suppressed by using the external preparation as a specific composition, so the necked container used in the present invention has a length on the lower side of the neck of 0.5 cm or more. Even if there is, the precipitation of menthol is suppressed. The lower length of the neck is usually less than 10 cm.

  Although the mouth part is not particularly limited, for example, the external preparation can be applied to the affected part by a mechanism such as sponge (sponge head) or roll-on (roll-on head).

  Hereinafter, the present invention will be described by way of examples, but the present invention is not limited to these examples and the like. In the table, units represent% by mass.

<Test Example 1>
As described in Table 1 (unit:% by mass), each component was weighed, weighed and dissolved to prepare a liquid composition.

  On a polypropylene resin sheet, 10 μL of each liquid composition was dropped with a pipetman, and the progress was observed. After 2 minutes from the dripping, the case where white turbidity was observed was shown as "x", and the case where white turbidity was not seen was shown in Table 1 as "(circle)." The follow-up observation results for Comparative Examples 1 and 2 and Examples 1 to 3 are shown in FIGS. 4 and 5.

  In Comparative Example 1, cloudiness due to precipitation was immediately observed, and in Example, cloudiness was suppressed. Similar results were obtained on a polyethylene resin sheet. In addition, when the wettability on a polypropylene resin sheet was visually observed, Comparative Examples 1 and 2 containing l-menthol and Examples 1 to 3 were all higher than the reference example not containing l-menthol. The

Test Example 2
The external preparation prepared in Examples 1 and 2 in a container of the brand name "Ammeltz Yokoko Yoko" (2017, Kobayashi Pharmaceutical Co., Ltd.) having an inclination angle of the neck to the longitudinal central axis of the body of about 60 °. Were filled and used as illustrated in FIG. 3 and then allowed to stand at 25 ° C. for 5 days as illustrated in FIG. No whitening was observed after standing.

1: Neck-bent container 11: body 12: neck 13: mouth 14: longitudinal central axis 15 of trunk: longitudinal central axis 16 of neck 16: lower length of neck 2: external preparation

Claims (5)

An external preparation comprising (a) an external preparation, and (b) a container for containing the external preparation (a),
Said external preparation (a) is:
At least one selected from the group consisting of loxoprofen and / or a pharmaceutically acceptable salt thereof;
menthol;
It is an external preparation containing an alcohol having 1 to 4 carbon atoms; and water.
The external preparation, wherein the container (b) comprises a body and a neck having a mouth, and the neck is inclined with respect to a central longitudinal axis of the body.   The external preparation according to claim 1, wherein the pharmaceutically acceptable salt of loxoprofen is loxoprofen sodium hydrate.   The external preparation according to claim 1, wherein the external preparation further contains a polyhydric alcohol.   The external preparation according to any one of claims 1 to 3, wherein the container is made of polyethylene or polypropylene.   The external preparation as described in any one of Claims 1-4 whose length below the said neck is 0.5-10 cm.