JP2015063486A - External composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an external composition comprising pyrroloquinoline quinone or pharmaceutically or physiologically acceptable salt thereof (PQQ or salt thereof), the external composition having excellent stability of PQQ or salt thereof, and having reduced variations in viscosity with time.SOLUTION: An external composition comprises (a) PQQ or salt thereof, (b) UVB absorber, and (c) silicon oil and/or ultraviolet absorber that absorbs ultraviolet in a UVA area.

Description

  The present invention includes pyrroloquinoline quinone (hereinafter sometimes abbreviated as “PQQ”), or a pharmaceutically or physiologically acceptable salt thereof (hereinafter sometimes abbreviated as “salt thereof”), The present invention relates to a composition for external use used as a cosmetic, a quasi-drug, or a pharmaceutical product.

PQQ exists widely in the living world such as plants, animals, and microorganisms, and functions as a redox coenzyme essential for energy acquisition.
PQQ is known to have many physiological activities and is expected to be used as an active ingredient in pharmaceuticals, quasi drugs, cosmetics, or supplements. As such physiological activity, active oxygen and radical scavenging action, cell growth promoting action, ultraviolet absorption action, nerve growth factor production promoting action, brain function improving action, hair growth action, facial color improving action, melanin production suppression or whitening action, Mitochondrial activation and anti-fatigue effects are known.

On the other hand, since PQQ shows very high reactivity, it is known that PQQ decomposition is accelerated, depending on the type of compounding ingredients in preparing the preparation. For example, it has been reported that PQQ easily reacts with amino group-containing substances such as amino acids, peptides, and proteins, and forms an imidazole skeleton in the structure to become an imidazolopyrroloquinoline compound.
Moreover, PQQ has poor light stability, and decomposition is promoted by light irradiation.

  If the PQQ content in the preparation decreases due to the decomposition of PQQ, the desired effect of PQQ cannot be obtained. In addition, degradation of PQQ and reaction may change the properties of the preparation and adversely affect the feeling of use. For example, in the case of a discoloration, dripping, or separation of ingredients in a cream or milky lotion, the value of the product is impaired visually and in terms of usability.

  In general, as an attempt to improve the stability of a specific component in a formulation, a method or derivative that suppresses a decomposition reaction caused by contact between the two components by forming a film on the specific component or a component that makes the component unstable Method, method of storing in a light-shielding container, composition containing the specific component and composition containing the component that destabilizes the component are stored in separate containers, and both compositions are mixed before use. There have been attempts to use them.

  However, conventional methods have difficulty in commercialization, for example, the degree of freedom of formulation is significantly limited and the cost of the container is increased.

  Here, in Patent Document 1, separation of oil-in-water emulsion sunscreen cosmetics containing an oil-soluble ultraviolet absorber, silicone oil, sorbitan stearate, ethanol, and an alkyl methacrylate methacrylate is suppressed. Teaches that it has excellent emulsification stability.

JP2011-219424

  An object of the present invention is to provide an external composition containing PQQ or a salt thereof, which is excellent in stability of PQQ or a salt thereof, and in which fluctuations in viscosity over time are suppressed. .

In order to improve the light stability of PQQ or a salt thereof in the composition for external use, the present inventor has conducted research to solve the above problems, and when a UVB absorber is added thereto, the stability of PQQ or a salt thereof is improved. Although the property was slightly improved, the problem was found that the viscosity of the composition was significantly reduced.
Moreover, the light stability of PQQ or a salt thereof is remarkably improved by blending a silicone oil and / or a UV absorber having a UV protection effect in the UVA region with a composition containing PQQ or a salt thereof and a UVB absorber. And it discovered that the viscosity of a composition became difficult to change.

This invention is completed based on the said knowledge, and provides the following external compositions.
Item 1. (a) pyrroloquinoline quinone, or a pharmaceutically or physiologically acceptable salt thereof, (b) a UVB absorber, and (c) a silicone oil and / or an ultraviolet absorber that absorbs ultraviolet rays in the UVA region. object.
Item 2. Item 2. The composition for external use according to Item 1, wherein the UVB absorber is a cinnamic acid derivative.
Item 3. Item 3. The composition for external use according to Item 2, wherein the cinnamic acid derivative is 2-ethylhexyl paramethoxycinnamate.
Item 4. Furthermore, the external composition in any one of claim | item 1 -3 containing an acrylic acid type | system | group thickener.
Item 5. Item 5. The external composition according to any one of Items 1 to 4, wherein the silicone oil is a straight silicone oil.
Item 6. Item 6. The external composition according to Item 5, wherein the straight silicone oil is at least one selected from the group consisting of linear dimethylpolysiloxane and methylphenylpolysiloxane.
Item 7. Item 6. The external composition according to Item 5, wherein the straight silicone oil is a volatile silicone oil.
Item 8. Item 8. The composition for external use according to any one of Items 1 to 7, wherein the ultraviolet absorber that absorbs ultraviolet rays in the UVA region is at least one selected from the group consisting of benzoylbenzoic acid derivatives and dibenzoylmethane derivatives.
Item 9. Item 9. The composition for external use according to any one of Items 1 to 8, comprising 0.01 to 30% by weight of the UVB absorber with respect to the total amount of the composition.
Item 10. Item 10. The external composition according to any one of Items 1 to 9, wherein the silicone oil is contained in an amount of 0.1 to 60% by weight based on the total amount of the composition.
Item 11. Item 11. The external composition according to any one of Items 1 to 10, comprising 0.01 to 30% by weight of an ultraviolet absorber that absorbs ultraviolet rays in the UVA region, based on the total amount of the composition.
Item 12. Item 12. The composition for external use according to any one of Items 1 to 11, which is used for protecting skin or hair from ultraviolet rays.

  Since PQQ or a salt thereof is very unstable to light, it is difficult to improve its light stability. However, according to the present invention, ultraviolet rays that absorb silicone oil and / or ultraviolet rays in the UVA region are used. By blending the absorber, the light stability of PQQ or a salt thereof can be practically sufficiently improved in an external composition containing PQQ or a salt thereof and a UVB absorber. In particular, silicone oil is a component that is widely used as a base, a dispersant, a release agent, an antifoaming agent, and the like of a composition for external use. The light stability of PQQ or a salt thereof can be obtained only by blending such components. It is surprising that the properties are significantly improved.

Moreover, when the viscosity of the composition for external use increases or decreases remarkably with time, the commercial value decreases for reasons such as worsening the feeling of use. The composition of the present invention contains a silicone oil and / or an ultraviolet absorber that absorbs ultraviolet rays in the UVA region, whereby a variation in viscosity of the preparation over time due to containing PQQ or a salt thereof and a UVB absorber (particularly, (Viscosity reduction) can be suppressed.
Therefore, the composition for external use of the present invention is a composition that is easy to manage during distribution and storage and has a high commercial value.
In addition, since the composition for external use of the present invention suppresses a change in viscosity over time, according to the present invention, PQQ or a salt thereof aiming at imparting pharmacological activity or physiological activity to a sunscreen composition containing a UVB absorber. Can be blended.

It is a figure which shows the evaluation result of the photostability of PQQ or its salt performed in the Example.

Hereinafter, the present invention will be described in detail.
The external composition of the present invention is an external composition comprising (a) PQQ or a salt thereof, (b) a UVB absorber, and (c) a silicone oil and / or an ultraviolet absorber that absorbs ultraviolet rays in the UVA region.

(a) PQQ or its salt PQQ exists in various organisms such as animals, plants, and bacteria, and therefore can be extracted from various organisms. Moreover, PQQ can purchase a commercial item.
Physiologically or pharmaceutically acceptable salts of PQQ include alkali metal salts such as sodium salt, potassium salt, and lithium salt; alkaline earth metal salts such as calcium salt and magnesium salt, and the like. . Among the salts, sodium salt, potassium salt, lithium salt, calcium salt, and magnesium salt are preferable.

The content of PQQ or a salt thereof in the composition is preferably 0.00001% by weight or more, more preferably 0.0001% by weight or more, and still more preferably 0.001% by weight or more with respect to the total amount of the composition. . If it is the said range, the physiological activity of PQQ or its salt will fully be obtained by the normal usage-amount of cosmetics, a quasi-drug, and a pharmaceutical external preparation.
Further, the content of PQQ or a salt thereof in the composition is preferably 1% by weight or less, more preferably 0.3% by weight or less, still more preferably 0.1% by weight or less, based on the total amount of the composition. 0.05 wt% or less is even more preferable, and 0.03 wt% or less is even more preferable. If it is the said range, the solubility in a formulation will be favorable, and it will become the thing excellent in the point of the external appearance as a composition for external use.

(b) UVB absorbers Examples of UVB absorbers include organic ultraviolet absorbers such as cinnamic acid derivatives, benzalmalonate derivatives, paraaminobenzoic acid derivatives, salicylic acid derivatives, benzophenone derivatives, benzylidene camphor derivatives, and phenylbenzoylimidazole derivatives. It is done.

  Examples of cinnamic acid derivatives include 2-methoxyhexyl paramethoxycinnamate (Ubinal MC80, Yubinal MC80N, BASF Japan; Parsole MCX, DSM Nutrition Japan), isoamyl methoxycinnamate (Neohelipan TS, Hermand Raymer) ), Isopropyl methoxycinnamate, cinnoxate, DEA methoxycinnamate, diisopropyl methylcinnamate, methylbis (trimethylsilon) silylisopentyl trimethoxycinnamate, methyl 2,5-diisopropylcinnamate, diparamethoxycinnamic acid Examples thereof include glyceryl mono-2-ethylhexanoate, 2-ethylhexyl α-cyano-β-phenylcinnamate (also known as Octocrylene, Pulsol 340, DSM Nutrition Japan).

  Examples of the benzalmalonate derivative include dimethicodiethylbenzalmalonate (Pulsol SLX, DSM Nutrition Japan).

  Examples of paraaminobenzoic acid derivatives include 2,4,6-tris [4- (2-ethylhexyloxycarbonyl) anilino] -1,3,5-triazine (Ubinal T150, BASF Japan Ltd.), paradimethylaminobenzoic acid. Examples include amyl, paradimethylaminobenzoic acid-2-ethylhexyl, paraaminobenzoic acid (PABA), glyceryl PABA, ethyl PABA, ethyl-dihydroxypropyl PABA, ethylhexyl-dimethyl PABA, and the like.

  Examples of salicylic acid derivatives include homomenthyl salicylate (Pulsol HMS, DSM Nutrition Japan), ethylhexyl salicylate (Neohelipan OS, Herman Andreimer), dipropylene glycol salicylate (Dipisar, Skell), TEA salicylate (Neohelipan) TS, Herman and Reimer), and ethylene glycol salicylate.

  Examples of benzophenone derivatives include benzophenone-1 (Ubinal 400, BASF Japan), benzophenone-2 (Ubinal D50, BASF Japan), benzophenone-3 (Ubinal M40, BASF Japan), benzophenone-4 (Ubinal MS40, BASF Japan), benzophenone-5 (Helisorb 11, Norquay), benzophenone-8 (Spectrasorb, American Cyanamide), benzophenone-9 (Ubinal DS49, BASF Japan) and the like.

  Examples of benzylidene camphor derivatives include 3-benzylidene camphor (Megizolyl SD, Simex), benzylidene camphor sulfonate (Megizolyl SL, Simex), methosulfate camphor benzalkonium (Megizolyl SO, Simex), polyacrylamidomethylbenzylidene Examples include camphor (Megizolyl SW, Simex).

  Examples of phenylbenzoylimidazole derivatives include phenylbenzimidazolesulfonic acid (Pulsol HS, DSM Nutrition Japan), disodium phenyldibenzimidazoletetrasulfonate (Neohelipan AP, Herman and Reimer), and the like.

Preferred B-wave absorbers include cinnamic acid derivatives such as 2-ethylhexyl paramethoxycinnamate, isopropyl paramethoxycinnamate, and 2-ethylhexyl α-cyano-β-phenylcinnamate (octocrylene); Paraaminobenzoic acids such as aminobenzoic acid, ethyl PABA, ethyl-dihydroxypropyl PABA, ethylhexyl-dimethyl PABA, 2,4,6-tris [4- (2-ethylhexyloxycarbonyl) anilino] -1,3,5-triazine Acid derivatives; salicylic acid derivatives such as homomenthyl salicylate, ethylhexyl salicylate; 3-benzylidene camphor, 4-methylbenzylidene camphor, benzylidene camphor sulfonic acid, camphor sulfate benzalkonium, polyacrylamide methylben Phenylbenzoyl imidazole derivatives such as phenyl dibenzimidazole tetrasulfonate disodium; benzylidenecamphor derivatives such as camphor, etc. benzalmalonate derivatives such as polyorganosiloxanes with benzalmalonate functional groups.
Among these, cinnamic acid derivatives are preferable, 2-ethylhexyl paramethoxycinnamate and 2-ethylhexyl α-cyano-β-phenylcinnamate are more preferable, and 2-ethylhexyl paramethoxycinnamate is most preferable.

  A UVB absorber can be used individually by 1 type or in combination of 2 or more types.

The content of the UVB absorber in the composition for external use is preferably 0.01% by weight or more, more preferably 0.05% by weight or more, and still more preferably 0.1% by weight or more based on the total amount of the composition. . If it is this range, PQQ or its salt can be kept stable in an external composition.
In addition, the content of the UVB absorber in the external composition is preferably 30% by weight or less, more preferably 20% by weight or less, and still more preferably 10% by weight or less, based on the total amount of the composition. If it is the said range, the fluctuation | variation of the viscosity of a composition will be suppressed and a favorable usability | use_condition will be obtained.

Further, the ratio of the content of the UVB absorber to the content of PQQ or a salt thereof is preferably 0.01 parts by weight or more, more preferably 0.1 parts by weight or more, with respect to 1 part by weight of PQQ or a salt thereof. 1 part by weight or more is even more preferable. If it is this range, PQQ or its salt can be kept stable in an external composition.
The ratio of the content of the UVB absorber to the content of PQQ or a salt thereof is preferably 20000 parts by weight or less, more preferably 5000 parts by weight or less, and 2000 parts by weight or less with respect to 1 part by weight of PQQ or a salt thereof. Is even more preferred. If it is the said range, the fluctuation | variation of the viscosity of a composition will be suppressed and a favorable usability | use_condition will be obtained.

(c) Silicone oil The silicone oil is not particularly limited as long as it is used for cosmetics, medicines, and external preparations for quasi drugs. Silicone oils are classified into straight silicone oils and modified silicone oils depending on the type of organic substituents bonded to silicon atoms. The straight silicone oil has a methyl group, a phenyl group, and a hydrogen atom as substituents, and the modified silicone oil has other organic substituents.

The straight silicone oils of the general formula _{(CH 3) 3 SiO - [} (CH 3) 2 SiO] n -Si (CH 3) 3 (n = 0~5) linear dimethylpolysiloxane (dimethicone represented by ); Ethyltrisiloxane; cyclic silicone oils such as methylcyclotetrasiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane (cyclopentasiloxane), dodecamethylcyclohexasiloxane; like diphenyl dimethicone, diphenylsiloxyphenyl trimethicone Methyl trimethylone ([(CH ₃ ) ₃ SiO] ₃ SiCH ₃ ); methyl hydrogen polysiloxane; dimethiconol and the like.
Among them, non-reactive ones are preferable in terms of excellent usability of the composition, and as such, linear dimethylpolysiloxane (dimethicone), methylphenylpolysiloxane such as diphenylsiloxyphenyltrimethicone, etc. Can be mentioned.
In addition, a volatile one is preferable in terms of excellent usability of the composition, and examples thereof include cyclic silicone oils such as cyclopentasiloxane, general formula (CH ₃ ) ₃ SiO — [(CH ₃ ) ₂ SiO ] linear dimethylpolysiloxane (dimethicone) represented by _{n -Si (CH 3) 3 (} n = 1~3) , and the like.

Further, as the modified silicone oil, non-reactive such as alkyl-modified silicone oil, alkoxy-modified silicone oil, alkyl / aralkyl-modified silicone oil, alkyl / polyether-modified silicone oil, polyether-modified silicone oil, higher fatty acid ester-modified silicone oil Reactive silicone oils such as amino-modified silicone oils, epoxy-modified silicone oils, and alcohol-modified silicone oils.
Among these, non-reactive modified silicone oil is preferable, and examples thereof include lauryl PEG-9 polydimethylsiloxyethyl dimethicone.

  One silicone oil can be used alone, or two or more silicone oils can be used in combination.

The content of the silicone oil in the composition for external use is preferably 0.1% by weight or more, more preferably 0.5% by weight or more, and still more preferably 1% by weight or more based on the total amount of the composition. If it is the said range, the light stability of PQQ or its salt will become favorable, and the fluctuation | variation of the viscosity of a composition will be suppressed.
Moreover, 60 weight% or less is preferable with respect to the whole quantity of a composition, and, as for content of the silicone oil in an external composition, 40 weight% or less is more preferable, and 20 weight% or less is still more preferable. If it is the said range, it will become a composition with a favorable usability | use_condition.

Further, the ratio of the content of silicone oil to the content of PQQ or a salt thereof is preferably 0.5 parts by weight or more, more preferably 25 parts by weight or more, and 50 parts by weight with respect to 1 part by weight of PQQ or a salt thereof. The above is even more preferable. If it is the said range, the light stability of PQQ or its salt will become favorable, and the fluctuation | variation of the viscosity of a composition will be suppressed.
The ratio of the content of silicone oil to the content of PQQ or a salt thereof is preferably 3000 parts by weight or less, more preferably 2500 parts by weight or less, and more preferably 2000 parts by weight or less with respect to 1 part by weight of PQQ or a salt thereof. Even more preferred. If it is the said range, it will become a composition with a favorable usability | use_condition.

The ratio of the silicone oil content to the UVB absorber content is preferably 0.01 parts by weight or more, more preferably 0.05 parts by weight or more, with respect to 1 part by weight of the UVB absorber. Even more preferred are parts by weight or more. If it is the said range, the light stability of PQQ or its salt will become favorable, and the fluctuation | variation of the viscosity of a composition will be suppressed.
The ratio of the silicone oil content to the UVB absorber content is preferably 600 parts by weight or less, more preferably 500 parts by weight or less, and even more preferably 400 parts by weight or less, relative to 1 part by weight of the UVB absorber. preferable. If it is the said range, it will become a composition with a favorable usability | use_condition.

(c) Ultraviolet absorber that absorbs ultraviolet rays in the UVA region As an ultraviolet absorber that absorbs ultraviolet rays in the UVA region, organic ultraviolet absorbers such as triazine derivatives, dibenzoylmethane derivatives, benzoylbenzoic acid derivatives, anthranyl derivatives, imidazoline derivatives, etc. Is mentioned.

  Examples of triazine derivatives include 2,4-bis-[{4- (2-ethylhexyloxy) -2-hydroxy} -phenyl] -6- (4-methoxyphenyl) -1,3,5-triazine (Tinosolve). S, BASF Japan), 2,2'-methylenebis (6- (2H-benzotriazol-2-yl) -4- (1,1,3,3-tetramethylbutyl) phenol (Tinosolve M, BASF Japan) ) And the like.

  Examples of the dibenzoylmethane derivative include 4-tert-butyl-4'-methoxydibenzoylmethane (Pulsol 1789, DSM Nutrition Japan).

  Examples of the benzoylbenzoic acid derivative include 2-[-4- (diethylamino) -2-hydroxybenzoyl] benzoic acid hexyl ester (Ubinal A plus, BASF Japan).

  Examples of anthranyl derivatives include menthyl anthranilate.

  Examples of imidazolidine derivatives include 2-methoxyhexyl dimethoxybenzylideneoxoimidazolidine propionate.

Preferred UV absorbers that absorb UV light in the UVA region include imidazolidine derivatives such as 2-methoxyhexyl dimethoxybenzylidene oxoimidazolidine propionate; anthranyl derivatives such as menthyl anthranilate; 2- [4- (diethylamino) -2 -Hydroxybenzoyl] benzoylbenzoic acid derivatives such as hexyl benzoate; dibenzoylmethane derivatives such as 4-tert-butyl-4'-methoxydibenzoylmethane; 2,4-bis-[{4- (2-ethylhexyl Oxy) -2-hydroxy} -phenyl] -6- (4-methoxyphenyl) -1,3,5-triazine, 2,2′-methylenebis (6- (2H-benzotriazol-2-yl) -4- And triazine derivatives such as (1,1,3,3-tetramethylbutyl) phenol.
Among them, benzoylbenzoic acid derivatives, dibenzoylmethane derivatives, and triazine derivatives are preferable, and hexyl 2- [4- (diethylamino) -2-hydroxybenzoyl] benzoate, 4-tert-butyl-4′-methoxydibenzoylmethane, 2 4-bis-[{4- (2-ethylhexyloxy) -2-hydroxy} -phenyl] -6- (4-methoxyphenyl) -1,3,5-triazine is more preferred.

  The ultraviolet absorber that absorbs ultraviolet rays in the UVA region in the present invention includes not only ultraviolet A waves but also ultraviolet absorbers that can absorb ultraviolet A waves and absorb ultraviolet rays in other wavelength regions. For example, the triazine derivative exemplified above as an ultraviolet absorber that absorbs ultraviolet rays in the UVA region can absorb ultraviolet B waves in addition to ultraviolet A waves. Such an ultraviolet absorber that absorbs both the ultraviolet A wave and the B wave is also included in the ultraviolet absorber that absorbs ultraviolet rays in the UVA region of the present invention. These ultraviolet absorbers can be combined in the skin external preparation of the present invention in an appropriate combination depending on the dosage form of the skin external preparation of the present invention to be prepared.

  The ultraviolet absorber which absorbs the ultraviolet-ray of a UVA area | region can be used individually by 1 type or in combination of 2 or more types.

The content of the ultraviolet absorber that absorbs ultraviolet rays in the UVA region in the composition for external use is preferably 0.01% by weight or more, more preferably 0.05% by weight or more, based on the total amount of the composition. Even more preferred is weight percent or more. If it is the said range, the light stability of PQQ or its salt will become favorable, and the fluctuation | variation of the viscosity of a composition will be suppressed.
The content of the ultraviolet absorber that absorbs ultraviolet rays in the UVA region in the composition for external use is preferably 30% by weight or less, more preferably 10% by weight or less, and more preferably 7% by weight or less based on the total amount of the composition. Even more preferred. If it is the said range, it will not become sticky, a creak will not generate | occur | produce, and it will become a composition with a favorable usability | use_condition.

Further, the ratio of the content of the ultraviolet absorber that absorbs ultraviolet rays in the UVA region to the content of PQQ or a salt thereof is preferably 0.2 parts by weight or more with respect to 1 part by weight of PQQ or a salt thereof. The above is more preferable, and 2 parts by weight or more is even more preferable. If it is the said range, the light stability of PQQ or its salt will become favorable, and the fluctuation | variation of the viscosity of a composition will be suppressed.
In addition, the ratio of the content of the ultraviolet absorber that absorbs ultraviolet rays in the UVA region to the content of PQQ or a salt thereof is preferably 30,000 parts by weight or less, and preferably 10,000 parts by weight or less with respect to 1 part by weight of PQQ or a salt thereof. More preferred is 7000 parts by weight or less. If it is the said range, the effect of this application can be exhibited.

In addition, the ratio of the content of the ultraviolet absorber that absorbs ultraviolet rays in the UVA region to the content of the UVB absorber is preferably 0.001 part by weight or more with respect to 1 part by weight of the UVB absorber, and 0.005 part by weight. The above is more preferable, and 0.01 parts by weight or more is even more preferable. If it is the said range, the light stability of PQQ or its salt will become favorable, and the fluctuation | variation of the viscosity of a composition will be suppressed.
In addition, the ratio of the content of the ultraviolet absorber that absorbs ultraviolet rays in the UVA region to the content of the UVB absorber is preferably 300 parts by weight or less, more preferably 100 parts by weight or less, with respect to 1 part by weight of the UVB absorber. 70 parts by weight or less is even more preferable. If it is the said range, the effect of this application can be exhibited.

  The content of the silicone oil and the ultraviolet absorber that absorbs ultraviolet rays in the UVA region when the silicone oil and the ultraviolet absorber that absorbs ultraviolet rays in the UVA region are included as the component (c) is the same as described above. .

Thickener The composition for external use of the present invention can contain a thickener, and thereby, the mixing property of PQQ which is a water-soluble compound or a salt thereof and an ultraviolet absorber which is usually a fat-soluble compound is good. Become.
As the thickener, for example, acrylic acrylic copolymer, acrylic methacrylate alkyl copolymer, (hydroxyethyl acrylate / acryloyldimethyltaurine sodium) copolymer, acrylic thickener such as carboxyvinyl polymer ( That is, (meth) acrylic acid monomer and / or (meth) acrylic acid alkyl monomer as a constituent polymer, copolymer, or crosspolymer); methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, Cellulosic thickeners such as carboxymethylcellulose and carboxyethylcellulose; hyaluronic acid, chondroitin sulfate, dermatan sulfate, kerato Mucopolysaccharides such as acids or salts thereof; thickening polysaccharides such as guar gum, locust bean gum, tamarind gum, carrageenan, xanthan gum, curdlan; polyvinyl alcohol; polyvinyl pyrrolidone; polyethylene glycol; bentonite; alginic acid; Etc.
Of these, acrylic thickeners such as acrylic acid acrylic copolymer, acrylic acid alkyl methacrylate copolymer, carboxyvinyl polymer, (hydroxyethyl acrylate / acryloyldimethyltaurine sodium) copolymer are preferred, and acrylic acid methacrylic acid is preferred. Alkyl copolymers are more preferred.

  A thickener can be used individually by 1 type or in combination of 2 or more types.

When the external composition of the present invention contains a thickener, the content thereof is preferably 0.001% by weight or more, more preferably 0.005% by weight or more, and 0.01% by weight based on the total amount of the composition. The above is even more preferable.
Moreover, 10 weight% or less is preferable with respect to the whole quantity of a composition, as for content of a thickener, 5 weight% or less is more preferable, and 1 weight% or less is still more preferable.
If it is the said range, the formulation excellent in the usability | use_condition can be produced.

pH
The pH of the composition of the present invention is preferably 2.5 or more, more preferably 3 or more, and even more preferably 4 or more. Moreover, 9 or less is preferable, 8.5 or less is more preferable, and 8 or less is still more preferable. If it is the said range, PQQ and its derivative (s) or its salt will be maintained stably.

Formulation Form The composition for external use of the present invention comprises (a) PQQ or a salt thereof, (b) a UVB absorber, and (c) a silicone oil and / or an ultraviolet absorber that absorbs ultraviolet rays in the UVA region. A pharmaceutically or physiologically acceptable base or carrier that can be used in an external product or cosmetic composition, and an external composition such as a pharmaceutical product, quasi-drug, or cosmetic product as necessary. It can mix with an additive and can be set as the external composition for pharmaceuticals, a quasi-drug, or cosmetics.

The form of the external composition for pharmaceuticals is not particularly limited, and examples thereof include liquids, suspensions, emulsions, creams, ointments, gels, liniments, lotions, and aerosols. These preparations can be manufactured according to the method described in the 16th revised Japanese Pharmacopoeia General Rules for Preparations.
Also when it is set as the composition for external use for quasi drugs or cosmetics, it can be made into the same form as said pharmaceutical. In addition, a stick agent, a sheet agent obtained by impregnating a non-woven fabric with a chemical solution, and the like can be given.

  Specifically, as an application in the case of a quasi-drug or cosmetic composition for external use, for example, lotion, emulsion, gel, cream, serum, sunscreen cosmetic, pack, mask, hand cream, Basic cosmetics such as lip balms, body lotions, and body creams; makeup cosmetics such as foundations, lipsticks, teak colors, and eye colors; and facial cleansers, makeup removers, body shampoos, shampoos, rinses, and treatments And cosmetics for cleaning. In addition, multifunctional preparations in which at least two preparation functions such as basic cosmetics, makeup cosmetics, and cleaning cosmetics are combined into one preparation are also included.

Bases or carriers Pharmaceutically or physiologically acceptable bases or carriers used in pharmaceutical compositions, quasi-drugs, cosmetics, etc., include squalane, petrolatum, α-olefin oligomers, and light Hydrocarbons such as liquid paraffin; higher alcohols such as cetanol, cetostearyl alcohol, stearyl alcohol, and behenyl alcohol; sterols such as cholesterol, phytosterol, and phytosteryl hydroxystearate; lanolin, orange raffii oil, squalane, and horses Animal oils such as oils; natural polymer derivatives such as ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, cationized guar gum, and acetylated hyaluronic acid; polyvinylpyrrolidone, carboxy Nyl polymers and synthetic polymers such as alkyl methacrylate methacrylate copolymers; natural polymers such as carrageenan, alginic acid, cellulose, guar gum, quince seed, dextran, gellan gum, and hyaluronic acid; isopropyl myristate, octyl myristate Dodecyl, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, pentaerythritol tetra-2-ethylhexanoate, jojoba oil, and esters such as tri (caprylic / capric) glyceryl, triethylhexanoin; dextrin, and Polysaccharides such as maltodextrin; lower alcohols such as ethanol and isopropanol; glycol ethers such as ethylene glycol monomethyl ether; polyethylene glycol Polyhydric alcohols such as cole, propylene glycol, 1,3-butylene glycol, glycerin, isoprene glycol, diglycerin, and dipropylene glycol; organic acids such as succinic acid, glycolic acid, gluconic acid, and citric acid; and water And an aqueous base.

  Among these, polyhydric alcohols, higher alcohols, hydrocarbons, esters, silicone oils, and organic acids are preferable, and polyhydric alcohols are more preferable. Among the polyhydric alcohols, 1,3-butylene glycol, propylene glycol, isoprene glycol, glycerin, diglycerin, and dipropylene glycol are preferable, and 1,3-butylene glycol, propylene glycol, glycerin, and diglycerin are more preferable. . Preferable examples of the composition of the present invention include solutions, lotions, creams, gels, emulsions, and ointments containing a lower alcohol and / or a polyhydric alcohol as a base.

When the composition for external use of the present invention contains water, the content thereof is preferably 5% by weight or more, more preferably 10% by weight or more, and still more preferably 20% or more, with respect to the total amount of the composition. Moreover, 80 weight% or less is preferable, 70 weight% or less is more preferable, and 50 weight% or less is still more preferable. When the composition for external use of the present invention is an emulsified composition, it may be O / W type or W / O type.
A base or a support | carrier can be used individually by 1 type or in combination of 2 or more types.

Additives In the composition of the present invention, additives that are added to compositions for external use such as pharmaceuticals, quasi-drugs, and cosmetics within the range not impairing the effects of the present invention, such as antioxidants and surfactants. , Preservatives, pH adjusters, stabilizers, irritation reducers, preservatives, colorants, fragrances, and / or pearlescent agents.

  Examples of the antioxidant include tocopherols, dibutylhydroxytoluene, butylhydroxyanisole, gallic acid esters and the like.

  Examples of the surfactant include sorbitan fatty acid esters such as sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate; propylene glycol fatty acid esters such as propylene glycol monostearate; Curing of polyoxyethylene hydrogenated castor oil 40 (HCO-40), polyoxyethylene hydrogenated castor oil 50 (HCO-50), polyoxyethylene hydrogenated castor oil 60 (HCO-60), and polyoxyethylene hydrogenated castor oil 80 Castor oil derivative; polyoxyethylene (20) sorbitan monolaurate (polysorbate 20), polyoxyethylene (20) sorbitan monostearate (polysorbate 60), polyoxyethylene monooleate (20 Sorbitan (polysorbate 80), and polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene (20) sorbitan isostearate; polyoxyalkylene alkyl ethers such as polyoxyethylene cetyl ether; phospholipids, surfactin, and saponins Natural surfactants; fatty acid amidoamines such as stearic acid diethylaminoethylamide and stearic acid diethylaminopropylamide; alkylamines such as trilaurylamine, dimethylstearylamine and di-2-ethylhexylamine; and dimethylaminopropylamide stearate And betaine amphoteric surfactants such as lauryl hydroxysulfobetaine.

  Examples of pH adjusters include inorganic acids (such as hydrochloric acid and sulfuric acid), organic acids (such as lactic acid, sodium lactate, citric acid, sodium citrate, succinic acid, and sodium succinate), inorganic bases (potassium hydroxide, And sodium hydroxide), and organic bases (such as triethanolamine, diisopropanolamine, and triisopropanolamine).

  Examples of the preservative include dehydroacetic acid and its salt, 2-methyl-4-isothiazolin-3-one, propyl iodide butylcarbamate, chlorobutanol, sorbic acid and its salt, glycerin fatty acid ester, parabens and the like. Can be mentioned.

  Examples of the stabilizer include sodium polyacrylate, ascorbic acid and its salts, erythorbic acid and its salts, sodium sulfite, sulfur disulfide and the like.

  An additive can be used individually by 1 type or in combination of 2 or more types.

Other Pharmacologically Active Component or Physiologically Active Component The composition for external use of the present invention can contain a pharmacologically active component or physiologically active component other than PQQ or a salt thereof as long as the effects of the present invention are not impaired.
Specific examples of pharmacologically active ingredients or physiologically active ingredients other than PQQ or salts thereof include, for example, moisturizing ingredients, anti-inflammatory ingredients, antibacterial or bactericidal ingredients, peptides or derivatives thereof, amino acids or derivatives thereof, keratin softening ingredients, and astringent ingredients Etc.

Examples of moisturizing ingredients include polyhydric alcohols such as glycerin, 1,3-butylene glycol, propylene glycol, polyethylene glycol, dipropylene glycol, sorbitol, xylitol, erythritol, and diglycerine; glucose, maltose, and trehalose. Macromolecules such as heparin analogs, sodium chondroitin sulfate, collagen, elastin, keratin, chitin, and chitosan; amino acids such as glycine and aspartic acid; such as sodium lactate, urea, and sodium pyrrolidonecarboxylate Natural moisturizing factors; lipids such as ceramide, cholesterol, and phospholipids.

  Examples of the anti-inflammatory component include a component derived from a plant (for example, Comfrey), allantoin, glycyrrhizic acid or a derivative thereof, zinc oxide, pyridoxine hydrochloride, salicylic acid or a derivative thereof, and ε-aminocaproic acid.

  Antibacterial or bactericidal components include, for example, chlorhexidine, salicylic acid, benzalkonium chloride, acrinol, sulfur, resorcin, ethanol, benzethonium chloride, adapalene, benzoyl peroxide, clindamycin, cresol, gluconic acid and its derivatives, popidone iodine, iodine Potassium iodide, iodine, isopropylmethylphenol, triclocarban, triclosan, photosensitizer 101, photosensitizer 201, glycerin fatty acid ester, alkyldiaminoglycine hydrochloride, chlorhexidine gluconate, zinc paraphenolsulfonate, and azelaic acid .

  Peptides or derivatives thereof include, for example, keratin-degrading peptide, hydrolyzed keratin, collagen, fish-derived collagen, atelocollagen, gelatin, elastin, elastin-degrading peptide, collagen-degrading peptide, hydrolyzed collagen, hydroxypropylammonium chloride hydrolyzed collagen, elastin Degraded peptide, conchiolin degrading peptide, hydrolyzed conchiolin, silk proteolytic peptide, hydrolyzed silk, lauroyl hydrolyzed silk sodium, soy proteolytic peptide, hydrolyzed soy protein, wheat protein, wheat proteolytic peptide, hydrolyzed wheat protein, casein Degraded peptides, acylated peptides (palmitoyl oligopeptides, palmitoyl pentapeptides, palmitoyl tetrapeptides, etc.) and the like can be mentioned.

  Examples of amino acids or derivatives thereof include betaine (trimethylglycine), proline, hydroxyproline, lysine, serine, glycine, alanine, phenylalanine, β-alanine, threonine, glutamic acid, glutamine, asparagine, aspartic acid, cysteine, cystine, methionine , Leucine, isoleucine, valine, histidine, taurine, γ-aminobutyric acid, γ-amino-β-hydroxybutyric acid, carnitine, carnosine, creatine and the like.

  Examples of the keratin softening component include urea, salicylic acid, glycolic acid, fruit acid, phytic acid, and sulfur.

Examples of the astringent component include zinc paraphenol sulfonate, zinc oxide, menthol, and ethanol.
Examples of the ultraviolet protection component include zinc silicate, cerium silicate, titanium silicate, zinc oxide, zirconium oxide, cerium oxide, titanium oxide, iron oxide and other inorganic compounds, and those inorganic compounds containing hydrous silicic acid and anhydrous silica. Coated with inorganic powder such as acid, aluminum hydroxide, mica and talc, compounded with resin powder such as polyamide, polyethylene, polyester, polystyrene and nylon, and further treated with silicone oil and fatty acid aluminum salt Things.

  Pharmacologically active ingredients or physiologically active ingredients other than PQQ or a salt thereof can be used alone or in combination of two or more.

Method of Use The composition for external use (skin preparation for external use) of the present invention varies depending on the condition, age, sex, etc. of the skin to be used, but may be used, for example, by the following method. That is, if it is applied several times a day (for example, about 1 to 5 times, preferably 1 to 3 times), an appropriate amount (for example, about 0.05 to 5 g) is applied to the skin by application, application, or spraying. Good. Further, the daily usage amount of PQQ or a salt thereof is, for example, about 0.0005 to 0.05 g, preferably about 0.001 to 0.02 g, more preferably about 0.002 to 0.01 g. What is necessary is just to apply | coat a composition. The application period is not particularly limited, and may be, for example, about 2 weeks to 6 months, preferably about 1 to 6 months.
The composition for external use of the present invention can be suitably used for people having various skin diseases and skin troubles, expecting the physiological activity of PQQ or a salt thereof. In particular, people who have wrinkles and tarmi, people whose skin texture is disturbed, and people with sensitive skin are suitable targets. In addition, in order to prevent skin troubles caused by photoaging, people with normal skin are also suitable for use.
The composition for external use of the present invention can also be suitably used as a sunscreen cosmetic for protecting skin and hair from ultraviolet rays, preventing sunburn, and a UV protective cosmetic.

In addition, the present invention provides (a) PQQ or a salt thereof, and (b) a composition containing UVB absorber (particularly a composition for external use), (c) a silicone oil and / or an ultraviolet absorber that absorbs ultraviolet rays in the UVA region. A method for improving the light stability of PQQ or a salt thereof, and a method for suppressing a change in viscosity (for example, a decrease in viscosity) of the composition (particularly a method for suppressing a change in viscosity (for example, a decrease in viscosity) at a high temperature). Is included.
In these methods, the type of each component, the content of each component, the pH of the composition, the properties of the composition, and the like are the same as those of the external composition of the present invention described above.

  EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated in detail, this invention is not limited to these Examples.

Test 1 (Evaluation of light stability of PQQ or its salt)
According to the composition of Table 1, PQQ · 2Na and (acrylates / alkyl acrylate (C10-30)) crosspolymer were weighed and dispersed in water, then swollen with potassium hydroxide and stirred to form an aqueous layer. To this aqueous layer, 2-ethylhexyl paramethoxycinnamate and a silicone component (oil layer) were added. The pH is then adjusted to 5.5 using potassium hydroxide. K. It stirred for 5 minutes at 1400 rpm using ROBOMICS (made by PRIMIX) (Examples 1-3).
In Comparative Example 1, the aqueous layer was diluted with purified water.
In Comparative Example 2, 2-ethylhexyl paramethoxycinnamate was added in Comparative Example 1, and in Comparative Examples 3 to 5, silicone oil was added in Comparative Example 1.

5 g of each formulation was dispensed into screw vials and sealed. All samples were irradiated with a total of 600,000 lx · hr (5000 lx for 120 hours) with a light stability test apparatus (“Light-Tron LT-120 D3CJ type, manufactured by Nagano Science Co., Ltd.). The content of PQQ · 2Na in each sample was quantified using high performance liquid chromatography.
The residual ratio of PQQ · 2Na after light irradiation was calculated according to the following formula.

PQQ · 2Na remaining rate (%)
= (PQQ · 2Na content of irradiated sample /
PQQ · 2Na content of unirradiated sample) x 100

  The results are shown in FIG. (a) By adding (b) 2-ethylhexyl paramethoxycinnamate to Comparative Example 1 containing only PQQ · 2Na (Comparative Example 2), the residual rate of PQQ · 2Na increased. In addition, Comparative Examples 3 to 5 containing (a) PQQ · 2Na and (c) silicone oil have almost the same light stability as PQQ · 2Na compared to Comparative Example 1 containing only (a) PQQ · 2Na. There was some improvement. In contrast, Examples 1 to 3 containing (a) PQQ · 2Na, (b) 2-ethylhexyl paramethoxycinnamate, and (c) silicone oil are (a), (b), and (c ) Synergistically improved the light stability of PQQ · 2Na.

Test 2 (Evaluation of viscosity stability)
According to the composition in Table 2, each preparation was prepared in the same manner as in Test Example 1. In this test, silicone oil was used as component (c).

Each example formulation was filled into a glass screw vial (capacity 30 mL) up to the top of the screw mouth and subjected to heat aging for 7 days in a 70 ° C. thermostat. Before and after thermal aging, the viscosity after 1 minute at 20 ° C. and 12 rpm was measured with a rotational viscometer (TVB-15M, rotor No. M-4, manufactured by Toki Sangyo Co., Ltd.). The viscosity change rate was calculated according to the following formula. Note that none of the preparations were separated or precipitated by the heat load.

Viscosity change rate (%)
= [(Viscosity after aging) / (viscosity before aging)] x 100

  The results are shown in Table 2. When (b) 2-ethylhexyl paramethoxycinnamate was added to (a) Comparative Example 6 containing only PQQ · 2Na (Comparative Example 7), the viscosity decreased significantly due to heat load. However, by adding (c) silicone oil to this, the decrease in viscosity due to heat load was completely suppressed (Example 4).

Test 3 (Evaluation of viscosity stability)
According to the composition shown in Table 3, each preparation was prepared in the same manner as in Test Example 1 except that the water layer and the oil layer were mixed by heating at 80 ° C. In this test, an ultraviolet absorber that absorbs ultraviolet rays in the UVA region was used as the component (c).

  Each formulation was subjected to heat aging in the same manner as in Test Example 2, the viscosity was measured in the same manner, and the viscosity change rate was calculated. Note that none of the preparations were separated or precipitated by the heat load.

The results are shown in Table 3. (a) When Comparative Example 8 containing PQQ · 2Na was added with 10% by weight of (b) 2-ethylhexyl paramethoxycinnamate (Comparative Example 9), as in Test Example 2, The viscosity dropped to 65% of the viscosity before aging. However, by adding (c) 4-tert-butyl-4′-methoxydibenzoylmethane to this, a decrease in viscosity due to heat load was completely suppressed (Example 5). Further, by adding 2-[-4- (diethylamino) -2-hydroxybenzoyl] benzoic acid hexyl ester, the decrease in viscosity could be kept to 76% of the viscosity before aging (Example 6).
Even when 7.5% of (b) 2-ethylhexyl paramethoxycinnamate was added to Comparative Example 8 containing PQQ · 2Na (Comparative Example 10), the viscosity of the preparation was 74% of the viscosity before aging due to heat load. It dropped to. By adding (c) 4-tert-butyl-4′-methoxydibenzoylmethane to this, a decrease in viscosity due to heat load was suppressed (Example 7).

Tables 4 to 7 below show formulation examples of the composition for external use of the present invention. The unit of numerical values in the table is w / w%.

  The composition for external use of the present invention has a high commercial value because it has excellent storage stability while containing PQQ or a salt thereof generally having poor light stability.

Claims (11)

  (a) pyrroloquinoline quinone, or a pharmaceutically or physiologically acceptable salt thereof, (b) a UVB absorber, and (c) a silicone oil and / or an ultraviolet absorber that absorbs ultraviolet rays in the UVA region. object.   The composition for external use according to claim 1, wherein the UVB absorber is a cinnamic acid derivative.   The composition for external use according to claim 2, wherein the cinnamic acid derivative is 2-ethylhexyl paramethoxycinnamate.   The composition for external use according to any one of claims 1 to 3, wherein the silicone oil is a straight silicone oil.   The composition for external use according to claim 4, wherein the straight silicone oil is at least one selected from the group consisting of linear dimethylpolysiloxane and methylphenylpolysiloxane.   The composition for external use according to claim 4, wherein the straight silicone oil is a volatile silicone oil.   The composition for external use according to any one of claims 1 to 6, wherein the ultraviolet absorber that absorbs ultraviolet rays in the UVA region is at least one selected from the group consisting of triazine derivatives, benzoylbenzoic acid derivatives, and dibenzoylmethane derivatives. .   The external composition in any one of Claims 1-7 which contains 0.01-30 weight% of UVB absorber with respect to the whole quantity of a composition.   The composition for external use in any one of Claims 1-8 which contains 0.1-60 weight% of silicone oil with respect to the whole quantity of a composition.   The composition for external use in any one of Claims 1-9 which contains 0.01-30 weight% of ultraviolet absorbers which absorb the ultraviolet-ray of a UVA area | region with respect to the whole quantity of a composition.   The composition for external use according to any one of claims 1 to 10, which is for protecting skin or hair from ultraviolet rays.