Composition containing benzoic acid amide compound and cyclodextrin solubilizer
阅读说明：本技术 含苯甲酸酰胺化合物及环糊精增溶剂的组合物 (Composition containing benzoic acid amide compound and cyclodextrin solubilizer ) 是由 李昌根 金洙镒 朴城逸 申洪柱 于 2018-03-26 设计创作，主要内容包括：本说明书涉及皮肤外用组合物,该组合物具有改善的溶解度及使用感,该组合物包括：作为其溶质的苯甲酸酰胺化合物、其异构物、其药学上可接受的盐、其水合物或其溶剂合物；及第一环糊精增溶剂。(The present specification relates to a composition for external application to the skin, which has improved solubility and feeling of use, comprising a benzoic acid amide compound, its isomer, its pharmaceutically acceptable salt, its hydrate or its solvate as a solute thereof, and th cyclodextrin solubilizer.)
A skin external composition, comprising:
a solute that is a compound represented by the following formula 1, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof; and
, wherein the solubilizer is cyclodextrin:
wherein R is1、R3And R4Are each independently selected from the group consisting of: hydrogen, hydroxy, C1To C5Alkoxy radical, C3To C6Cycloalkoxy, aryloxy and C1To C5A haloalkoxy group which is a halogen atom,
R2selected from the group consisting of: hydrogen, C1To C5Alkyl radical, C3To C6Cycloalkyl, aryl and C1To C5A haloalkyl group, and
n is an integer selected from 1 to 5.
2. The composition for external application to skin according to claim 1,
characterized in that R of formula 11、R3And R4Each independently selected from the group consisting of: hydrogen, hydroxy, C1To C3Alkoxy radical, C3To C6Cycloalkoxy, aryloxy and C1To C3A haloalkoxy group which is a halogen atom,
R2selected from the group consisting of: hydrogen, C1To C3Alkyl radical, C3To C6Cycloalkyl, aryl and C1To C3A haloalkyl group, and
n is an integer selected from 1 to 3.
3. The composition for external application to skin according to claim 2,
wherein the solute is a compound selected from the group consisting of:
5-adamantan-1-yl-N- [2- (3, 4-dihydroxyphenyl) -ethyl ] -2, 4-dihydroxy-benzoic acid amide,
5-adamantan-1-yl-N- [2- (3, 4-dihydroxyphenyl) -ethyl ] -2-hydroxy-4-methoxy-benzoic acid amide,
5-adamantan-1-yl-N- (3, 4-dihydroxybenzyl) -2, 4-dihydroxy-benzoic acid amide,
5-adamantan-1-yl-N- (3, 4-dihydroxybenzyl) -2-hydroxy-4-methoxy-benzoic acid amide,
5-adamantan-1-yl-2, 4-dihydroxy-N- [2- (4-hydroxyphenyl) -ethyl ] -benzoic acid amide,
5-adamantan-1-yl-2-hydroxy-N- [2- (4-hydroxyphenyl) -ethyl ] -4-methoxy-benzoic acid amide,
5-adamantan-1-yl-N- [2- (4-hydroxyphenyl) -ethyl ] -2, 4-dimethoxy-benzoic acid amide,
5-adamantan-1-yl-N- (2, 4-dihydroxybenzyl) -2, 4-dihydroxy-benzoic acid amide,
5-adamantan-1-yl-N- (2, 4-dihydroxybenzyl) -2-hydroxy-4-methoxy-benzoic acid amide,
5-adamantan-1-yl-N- (2, 4-dihydroxybenzyl) -2, 4-dimethoxy-benzoic acid amide,
3-adamantan-1-yl-N- (3, 4-dihydroxybenzyl) -4-hydroxy-benzoic acid amide,
3-adamantan-l-yl-N- (3, 4-dihydroxybenzyl) -4-methoxy-benzoic acid amide,
3-adamantan-1-yl-N- [2- (3, 4-dihydroxyphenyl) -ethyl ] -4-hydroxy-benzoic acid amide,
3-adamantan-1-yl-N- [2- (3, 4-dihydroxyphenyl) -ethyl ] -4-methoxy-benzoic acid amide,
3-adamantan-1-yl-4-hydroxy-N- [2- (4-hydroxyphenyl) -ethyl ] -benzoic acid amide,
3-adamantan-l-yl-N- [2- (4-hydroxyphenyl) -ethyl ] -4-methoxy-benzoic acid amide,
3-adamantan-1-yl-N- (2, 4-dihydroxybenzyl) -4-hydroxy-benzoic acid amide,
3-adamantan-1-yl-N- (2, 4-dihydroxybenzyl) -4-methoxy-benzoic acid amide,
5-adamantan-1-yl-N- (2, 5-dimethoxybenzyl) -2, 4-dihydroxy-benzoic acid amide,
5-adamantan-1-yl-N- (2, 5-dihydroxybenzyl) -2, 4-dihydroxy-benzoic acid amide,
5-adamantan-1-yl-N- (3, 5-dimethoxybenzyl) -2, 4-dihydroxy-benzoic acid amide and
5-adamantan-1-yl-2, 4-dihydroxy-N- (3-hydroxy-5-methoxybenzyl) -benzoic acid amide, its isomers, its pharmaceutically acceptable salts, its hydrates, or its solvates.
4. The composition for external application to skin according to claim 3,
the solute is 5-adamantane-1-yl-N- (2, 4-dihydroxy benzyl) -2, 4-dimethoxy-benzoic acid amide.
5. The composition for external application to skin according to claim 1,
the cyclodextrin is characterized in that the cyclodextrin is at least selected from α -cyclodextrin, β -cyclodextrin, gamma-cyclodextrin, hydroxypropyl- α -cyclodextrin, hydroxypropyl- β -cyclodextrin and hydroxypropyl-gamma-cyclodextrin.
6. The composition for external application to skin according to claim 1,
characterized in that the weight ratio of the solute to the th solubilizer is 1:0.1 to 100.
7. The composition for external application to skin according to claim 5,
it is characterized in that the th solubilizer is hydroxypropyl- β -cyclodextrin and the weight ratio of the solute to the th solubilizer is 1:2 to 100.
8. The composition for external application to skin according to claim 5,
it is characterized in that the th solubilizer comprises hydroxypropyl- β -cyclodextrin and gamma-cyclodextrin in a weight ratio of 1: 0.1-10, and the weight ratio of the solute to the th solubilizer is 1: 0.1-100.
9. The composition for external application to skin according to claim 1,
characterized in that the composition for external application to skin further comprises a pH adjusting agent.
10. The composition for external application to skin according to claim 9,
characterized in that the pH regulator comprises at least of potassium hydroxide (KOH) and calcium hydroxide (Ca (OH)2) Sodium carbonate (Na)2CO3) Potassium carbonate (K)2CO3) Sodium bicarbonate (NaHCO)3) Lithium hydroxide (LiOH), citric acidLactic acid, 2-aminobutanol, acetic acid, acetylmandelic acid, adipic acid, aluminum hydroxide, aluminum tri-formate, aminoethylpropanediol, aminomethylpropanediol, aminomethylpropanol, aminopropanediol, ammonia, ammonium bicarbonate, ammonium carbamate, ammonium carbonate, ammonium glycolate, ammonium hydroxide, ammonium phosphate, ascorbic acid, azelaic acid, babassu seed oil acid, diphenylglycolic acid, benzoic acid, bis-hydroxyethyl trimethylolmethylamine, butyldiethanolamine, butylethanolamine, calcium citrate, calcium dihydrogen phosphate, calcium glycinate, calcium oxide, camphorsulfonic acid, chloroacetic acid, copper glycinate, dibutylethanolamine, diethanolamine bisulfate, diisopropanolamine, diisopropylamine, dimethylisopropanolamine, dimethylMEA, dioleoyl edethanol ammonium methylsulfate, dioleyl phosphate, dipotassium hydrogen phosphate, dipropylene triamine, disodium fumarate, disodium phosphate, disodium pyrophosphate, disodium tartrate, ethanolamine hydrochloride, ethylethanolamine, formic acid, fumaric acid, galacturonic acid, geranic acid, glucoheptonic acid, glucosamine hydrochloride, glucuronic acid, glutaric acid, glycolic acid, glyoxylic acid, guanidine carbonate, hydrobromic acid, hydrochloric acid, imidazole, isopropanolamine, isopropylamine, ketoglutaric acid, lactobionic acid, lithium carbonate, magnesium bicarbonate, magnesium glycinate, magnesium hydroxide, magnesium oxide, maleic acid, malic acid, malonic acid, maltobionic acid, metaphosphoric acid, methoxy PEG-100/polyepsilon caprolactone ethylhexanoate, methoxy PEG-100/polyepsilon caprolactone palmitate, methoxy PEG-114/polyepsilon caprolactone, methylethanolamine, methylglucamine, morfolin, morfozoline-substituted propanesulfonic acid, oxalic acid, p-anisic acid, potassium tripolyphosphate, pentasodium tripolyphosphate, phenol red, phosphoric acid, potassium bicarbonate, potassium hydrogen phthalate, potassium borate, potassium citrate, magnesium potassium aspartate, potassium oxide, potassium phosphate, potassium tartrate, propionic acid, quinic acid, ribonic acid, sebacic acid, triethanolamine sesquiethoxide, sodium aluminate, sodium anisate, sodium arachidate, sodium bisulfate, sodium borate, calcium sodium borophosphate, copper sodium calcium phosphate, calcium sodium phosphate, sodium cinnamoate, sodium citrate, sodium cyanate, sodium fumarate, sodium glycolate, sodium hydroxide, sodium oxide, sodium sesquicarbonate, sodium silicate, sodium succinate, sodium trimetaphosphate, sodium lactateSodium tungstate antimonate, strontium hydroxide, succinic acid, sulfonated styrene/DVB crosspolymer, sulfuric acid, tartaric acid, TEA-di-ricinoleate/IPDI copolymer, tetrapotassium pyrophosphate, tetrasodium pyrophosphate, triethanolamine, triisopropanolamine, trisodium phosphate, trisodium sulfosuccinate, tromethamine, vinegar, zinc carbonate hydroxide, zinc glycinate, and magnesium zinc aspartate.
11. The composition for external application to skin according to claim 9,
characterized in that, when the pH of the skin external composition is 2 or more, the weight ratio of the solute to the th solubilizer is 1:0.1 to 50.
12. The composition for external application to skin according to claim 11,
characterized in that, when the pH of the skin external composition is 2 to 10, the weight ratio of the solute to the th solubilizing agent is 1:4 to 12 and the th solubilizing agent is hydroxypropyl- β -cyclodextrin.
13. The composition for skin external use according to any of claims 1 to 12,
characterized in that the solute is present in an amount of 0.01 to 20% by weight relative to the total weight of the composition.
14. The composition for skin external use according to any of claims 1 to 12,
characterized in that the composition comprises a second solubilizer selected from at least selected from the group consisting of xanthan gum, hydroxypropyl methylcellulose, sodium polyacrylate, sodium magnesium silicate, hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer, polyacrylate-13/polyisobutylene/polysorbate-20, PEG-240/HDI copolymer bis-decyltetradecyltetradecylpolyether-20 ether, and magnesium aluminum silicate.
15. The composition for skin external use according to any of claims 1 to 12,
characterized in that the composition for external application to the skin is a composition for whitening the skin.
16. The composition for skin external use according to any of claims 1 to 12,
characterized in that the skin external composition is a pharmaceutical composition or a cosmetic composition.
[ technical field ] A method for producing a semiconductor device
The present application relates to a composition for external use on skin, comprising a solute which is a benzoic acid amide compound, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof; and a cyclodextrin solubilizer, and the composition has improved solubility.
[ Prior Art ]
Melanin is a major determinant of skin color, and is a cause of pigmentation (pigmentation) such as liver spots (melasma), freckles (freckles), nevus (nevus) and the like when melanin is excessive, melanin is produced by melanocytes, which are present in the basal layer of the skin (basal layer), it is known that stimulation of ultraviolet rays or inflammation promotes melanin production, and thus melanin production can be reduced by reducing external stimulation, blocking signal transduction, or inhibiting the synthesis of melanin-producing tyrosinase (tyrosinase) or inhibiting its activity, kojic acid (kojic acid), hydroquinone (hydroquinone), arbutin (arbutin), azelaic acid (aacid), aloesin (aloesin), 4-butylresorcinol (4-butylresorcinol), resveratrol (resveratrol), ceramide (ceramide), sphingosine (sphingosine-1), and sphingosine-1-phosphate, which are not regulated by these substances, but have been studied for superior skin whitening effect, and for its inhibitory effect on melanin production, such as a low inhibitory effect.
Broussonetia kazinoki (Broussonetia kazinoki) has been conventionally used as a raw material for producing korean hand sheets, it has been predicted that Broussonetia kazinoki has a skin whitening effect from the fact that hands of people who make korean hand sheets are white and thin, and thus, scientific research has been conducted to show that roots of Broussonetia kazinoki contain broussonetol (kazinol), which is a component having an excellent whitening effect, "Broussonetia extract" has also been announced as a functional cosmetic raw material by the korea food and drug safety department.
Dihydroxybenzyladamantane Dimethoxybenzamide (DBAB) is a newly developed compound based on 3D-QSAR analysis of quantitative structure-activity relationship (QSAR) and 100 derivatives obtained by modeling the trace element structure of broussonetia, broussonetia F, and in consideration of efficacy, stability, and manufacturability. It was found that this compound exhibits a novel whitening effect by the following mechanism: the compound reduces MITF expression through cAMP-PKA-CREB signaling pathway and thus inhibits the activity of tyrosinase, TRP-1 and TRP-2, which are major proteins involved in and regulated by MITF, thus inhibiting melanin synthesis. This effect was verified by cellular and artificial skin tests.
However, there has been no study aimed at improving the solubility of a composition containing a benzoic acid amide material. The present inventors have conducted studies on a composition of a benzoic acid amide substance having improved solubility, and thus have completed the present invention.
[ summary of the invention ]
[ problem ] to
In view of the above problems, the present inventors have conducted studies on a composition including a solubilizing agent for improving the solubility of a composition including a benzoic acid amide compound, resulting in the present invention.
An aspect of the present invention is to provide a composition that improves the solubility of benzoic acid amide compounds without adversely affecting the feel of use.
[ problem solution ]
The aspect of the present invention provides a composition for external application to the skin, comprising a solute which is a compound represented by the following
[ formula 1]
In the
R1、R3and R4Each independently selected from the group consisting of: hydrogen, hydroxy, C1To C5Alkoxy radical, C3To C6Cycloalkoxy, aryloxy and C1To C5A haloalkoxy group which is a halogen atom,
R2selected from the group consisting of: hydrogen, C1To C5Alkyl radical, C3To C6Cycloalkyl, aryl and C1To C5Haloalkyl, and
n is an integer selected from 1 to 5.
In aspect of the invention, R of
R2may be selected from the group consisting of: hydrogen, C1To C3Alkyl radical, C3To C6Cycloalkyl, aryl and C1To C3A haloalkyl group, and
n may be an integer selected from 1 to 3.
In the aspect of the invention, the solute may be a compound selected from the group consisting of:
5-adamantan-1-yl-N- [2- (3, 4-dihydroxyphenyl) -ethyl ] -2, 4-dihydroxy-benzoic acid amide,
5-adamantan-1-yl-N- [2- (3, 4-dihydroxyphenyl) -ethyl ] -2-hydroxy-4-methoxy-benzoic acid amide,
5-adamantan-1-yl-N- (3, 4-dihydroxybenzyl) -2, 4-dihydroxy-benzoic acid amide,
5-adamantan-1-yl-N- (3, 4-dihydroxybenzyl) -2-hydroxy-4-methoxy-benzoic acid amide,
5-adamantan-1-yl-2, 4-dihydroxy-N- [2- (4-hydroxyphenyl) -ethyl ] -benzoic acid amide,
5-adamantan-1-yl-2-hydroxy-N- [2- (4-hydroxyphenyl) -ethyl ] -4-methoxy-benzoic acid amide,
5-adamantan-1-yl-N- [2- (4-hydroxyphenyl) -ethyl ] -2, 4-dimethoxy-benzoic acid amide,
5-adamantan-1-yl-N- (2, 4-dihydroxybenzyl) -2, 4-dihydroxy-benzoic acid amide,
5-adamantan-1-yl-N- (2, 4-dihydroxybenzyl) -2-hydroxy-4-methoxy-benzoic acid amide,
5-adamantan-1-yl-N- (2, 4-dihydroxybenzyl) -2, 4-dimethoxy-benzoic acid amide,
3-adamantan-1-yl-N- (3, 4-dihydroxybenzyl) -4-hydroxy-benzoic acid amide,
3-adamantan-l-yl-N- (3, 4-dihydroxybenzyl) -4-methoxy-benzoic acid amide,
3-adamantan-1-yl-N- [2- (3, 4-dihydroxyphenyl) -ethyl ] -4-hydroxy-benzoic acid amide,
3-adamantan-1-yl-N- [2- (3, 4-dihydroxyphenyl) -ethyl ] -4-methoxy-benzoic acid amide,
3-adamantan-1-yl-4-hydroxy-N- [2- (4-hydroxyphenyl) -ethyl ] -benzoic acid amide,
3-adamantan-l-yl-N- [2- (4-hydroxyphenyl) -ethyl ] -4-methoxy-benzoic acid amide,
3-adamantan-1-yl-N- (2, 4-dihydroxybenzyl) -4-hydroxy-benzoic acid amide,
3-adamantan-1-yl-N- (2, 4-dihydroxybenzyl) -4-methoxy-benzoic acid amide,
5-adamantan-1-yl-N- (2, 5-dimethoxybenzyl) -2, 4-dihydroxy-benzoic acid amide,
5-adamantan-1-yl-N- (2, 5-dihydroxybenzyl) -2, 4-dihydroxy-benzoic acid amide,
5-adamantan-1-yl-N- (3, 5-dimethoxybenzyl) -2, 4-dihydroxy-benzoic acid amide, and
5-adamantan-1-yl-2, 4-dihydroxy-N- (3-hydroxy-5-methoxybenzyl) -benzoic acid amide, its isomers, its pharmaceutically acceptable salts, its hydrates, or its solvates.
In the aspect of the invention, the solute may be 5-adamantan-1-yl-N- (2, 4-dihydroxybenzyl) -2, 4-dimethoxy-benzoic acid amide.
In the aspect of the invention, the cyclodextrin can be at least of α -cyclodextrin, β -cyclodextrin, γ -cyclodextrin, hydroxypropyl- α -cyclodextrin, hydroxypropyl- β -cyclodextrin (HP- β -CD), and hydroxypropyl- γ -cyclodextrin.
In the aspect of the invention, the weight ratio of the solute to the solubilizing agent can be 1:0.1 to 100.
In the aspect of the invention, the solubilizing agent can be hydroxypropyl- β -cyclodextrin and the weight ratio of the solute to the solubilizing agent can be 1:2 to 100.
In the aspect of the invention, the solubilizing agent can include hydroxypropyl- β -cyclodextrin and gamma-cyclodextrin in a weight ratio of 1:0.1 to 10, and the weight ratio of the solute to the solubilizing agent can be 1:0.1 to 100.
Another aspect of the invention provides a topical composition for skin comprising steps of a pH adjusting agent.
In another aspect of the invention, the pH adjusting agent can be at least of potassium hydroxide (KOH), calcium hydroxide (Ca (OH)2) Sodium carbonate (Na)2CO3) Potassium carbonate (K)2CO3) Sodium bicarbonate (NaHCO)3) Lithium hydroxide (LiOH), citric acid (citric acid), lactic acid (lactic acid), 2-aminobutanol (2-aminobutanol), acetic acid (acetic acid), acetylmandelic acid (acetyl mandelic acid), adipic acid (adipoic acid), aluminum hydroxide oxide (aluminum hydroxide oxide), aluminum trimethyl oxide (aluminum triformate), aminoethylpropanediol (aminoethylpropanediol)ethylene glycol, aminomethylpropanediol (aminomethylpropanediol), aminomethylpropanol (aminomethylpropanol), aminopropanediol (aminopropanediol), ammonia (ammonia), ammonium bicarbonate (ammonium bicarbonate), ammonium carbamate (ammonium carbonate), ammonium carbonate (ammonium carbonate), ammonium glycolate (ammonium glycolate), ammonium hydroxide (ammonium hydroxide), ammonium phosphate (ammonium phosphate), ascorbic acid (ascorbic acid), azelaic acid (azelaic acid), babassu oil acid (basic acid), diphenylglycolic acid (benzilic acid), benzoic acid (benzilic acid), bis-hydroxyethyl-trimethylol methylamine (bis-hydroxymenthyl methylamine), butyldiethanolamine (butyl diethanolamine), butylethanolamine (butyl ethanolamine), butyldiethanolamine (butyl glycolate), calcium citrate (calcium citrate), calcium phosphate (calcium phosphate), calcium chloride (calcium chloride), dibutylethanolamine (dibutyl ethanolamine), diethanolamine (diethanol amine), diethanolamine bisulfate (diethanol amine), diisopropanolamine (diisopropanolamine), dimethylisopropanolamine (dimethyl isopropanolamine), dimethylMEA (dimethyl MEA), dioleoyl edetate (dioleoyl ethylene monomethylsulfate), dioleyl phosphate (dioleyl phosphate), dipotassium hydrogen phosphate (dipotassium phosphate), dipropylene triamine (dipropyleneamine), disodium fumarate (disodidium fumarate), disodium phosphate (disodidium pyrophosphate), disodium pyrophosphate (disodiphosphate), disodium tartrate (disodized ethanolamine), ethanolamine (hydrochloric acid), ethyleneglycollate (citric acid), citric acid (glycolic acid), gluconic acid (citric acid), gluconic acid (HCl), gluconic acid (citric acid hydrochloride), gluconic acid (citric acid), gluconic acid (citric acid hydrochloride), glutaric acid (glutaric acid), glycolic acid (glycolic acid), glyoxylic acid (glycoxylic acid), guanidine carbonate (guanidinium carbonate), hydrobromic acid (hydrobromic acid), hydrochloric acid (hydrochloric acid), imidazole (imidazole), isopropanol (isopropanol), and mixtures thereofAmine (isoproapanamine), isopropylamine (isoproylamamine), ketoglutaric acid (ketoglutaric acid), lactobionic acid (lactobionic acid), lithium carbonate (lithium carbonate), magnesium carbonate (magnesium carbonate), magnesium bicarbonate (magnesium carbonate), magnesium glycinate (magnesium glycinate), magnesium hydroxide (magnesium hydroxide), magnesium oxide (magnesium oxide), maleic acid (maleic acid), malic acid (maleic acid), malonic acid (malonic acid), maltogenic acid (maltogenic acid), metaphosphoric acid (methylphosphonic acid), methoxy PEG-100/polyepsilon ethylhexanoate (methoxy PEG-100/polycaprolactone), methoxy PEG-100/polycaprolactone (methyl PEG-100/polycaprolactone), poly (methyl glycine/caprolactone)/poly (ethylene glycol/methyl ethanolamine) (PEG-114), morpholine propanesulfonic acid (morpholinopropanesulfonic acid), oxalic acid (oxoacetic acid), p-anisic acid (p-anisic acid), potassium tripolyphosphate (pentasodium tripolyphosphate), pentasodium tripolyphosphate (pentasodium tripolyphosphate), phenol red (phenosulfonate), phosphoric acid (phosphoric acid), potassium bicarbonate (potassium bicarbonate), potassium hydrogen phthalate (potassium biphthalate), potassium phosphate (potassium borate), potassium borate (potassium borate), magnesium aspartate (potassium aspartate), potassium oxide (potassium oxide), potassium phosphate (potassium phosphate), potassium tartrate (potassium tartrate), sodium aluminate (potassium propionate), sodium citrate (sodium citrate), sodium aluminate (potassium propionate), sodium borate (potassium citrate), sodium aluminate (potassium citrate), sodium oleate (potassium oleate), sodium stearate (sodium stearate), sodium stearate (sodium oleate), sodium oleate (sodium oleate, sodium oleate (citrate), sodium stearate), potassium oleate (sodium stearate), sodium stearate (sodium stearate), sodium oleate (sodium stearate), potassium stearate (sodium stearate), sodium oleate (sodium stearate), sodium stearate (sodium oleate (sodium stearate), sodium oleate (sodium stearate), sodium stearate (sodium stearate), sodium oleate (sodium stearate), sodium stearate (sodium stearate), sodium calcium phosphate copper (phosphate), sodium phosphate calcium (phosphate), sodium cinnamate (cinnamate), sodium citrate (citrate), sodium cyanate (cyanate), sodium fumarate (fumarate), sodium glycolate (glycolate), and sodium hydroxide (sodium hy)Hydroxide, sodium oxide (sodium oxide), sodium sesquicarbonate (sodium sesquicarbonate), sodium silicate (sodium silicate), sodium succinate (sodium succinate), sodium trimetaphosphate (sodium trimetaphosphate), sodium tungstate antimonate (sodium tungstate antimonate), strontium hydroxide (strontium hydroxide), succinic acid (succinic acid), sulfonated styrene/DVB crosspolymer (sulfonated styrene/DVB crosslinker), sulfuric acid (sulfururic acid), tartaric acid (tartaric acid), TEA-di-ricinoleate/IPDI copolymer (TEA-di-ricinoleate/IPDI copolymer), tetrapotassium pyrophosphate (tetrapotassium pyrophosphate), tetrasodium pyrophosphate (tetraphosphorous phosphate), triethanolamine (triisopropanolamine), trisodium carbonate (triisopropanolamine), zinc succinate (zinc succinate), zinc succinate (potassium phosphate), zinc succinate (sodium succinate), and zinc succinate).
In another aspect of the invention, when the pH of the skin external composition is 2 or higher, the weight ratio of the solute to the solubilizing agent can be 1:0.1 to 50.
In another aspect of the invention, when the pH of the skin external composition is 2 to 10, the weight ratio of the solute to the th solubilizing agent can be 1:4 to 12, and the th solubilizing agent can be hydroxypropyl- β -cyclodextrin.
In the or aspects of the invention, the solute content can be 0.01 wt.% to 20 wt.% based on the total weight of the composition.
In or aspects of the invention, the composition may further comprise a second solubilizer selected from at least of the group consisting of xanthan gum (xanthan gum), hydroxypropyl methylcellulose (hydroxypropyl methyl cellulose), sodium polyacrylate (sodium polyacrylate), sodium magnesium silicate (sodium magnesium silicate), hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer (hydroxyethyl acrylate/sodium acryloyldimethyl sulfate copolymer), polyacrylate-13/polyisobutylene/polysorbate-20 (polyacrylate-13/isobutylene/polysorbate-20), PEG-240/HDI copolymer bis-decyltetradecylpental polyether-20 ether (PEG-240/chitosan-20) and magnesium aluminum silicate (magnesium aluminum silicate).
In or aspects of the invention, the composition can further comprise step a third solubilizing agent which is at least of diethylene glycol ethyl ether (diethylene glycol monoethyl ether), methyl gluceth (methyl gluceth), glycerol ether (glycerol ether), polyethylene glycol (polyethylene glycol), and polyethylene glycol/polypropylene glycol (polyethylene glycol/polypropylene glycol) copolymers.
In another aspect of the present invention, the skin external composition is provided as a skin whitening composition.
In another aspect of the present invention, the skin external composition is provided as a pharmaceutical composition or a cosmetic composition.
[ advantageous effects of the invention ]
In the composition according to the aspect of the invention , the solute has excellent solubility, and the solute is a benzoic acid amide compound, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof.
In the composition according to the aspect , the benzoic acid amide compound as the solute does not precipitate.
The composition of the aspect of the invention has excellent solubility and excellent feel in use when applied to the skin.
[ brief description of drawings ]
FIG. 1 is a photograph showing the solubility of DBAB and HP- β -CD of test example 1 according to the present invention at various weight ratios.
FIG. 2 photo of the composition of Table 3 of test example 3 of the present invention.
FIG. 3 is a polarization microscope photograph of example 4 of test example 5 of the present invention.
[ detailed description ] embodiments