KR20090021501A - Composition for external use containing stable benzamide compounds obtained by controlling ph of the composition, and method for stabilizing the benzamide compounds - Google Patents

Abstract

Provided is a method for stabilizing benzamide compounds to manufacture skin medicines for external use, including the benzamide compounds as an active ingredient without any structure changes. A composition of skin medicines for external use has pH of 5 or less. Benzamide compounds of which a substituted group is not decomposed exists within the composition. The benzamide compounds are selected from the group consisting of 3,5-dihydroxy-N-(4-hydroxyphenyl)benzamide, N-Phenylbenzamide, t-butylbenzamido hydroxybenzamide, 2-hydroxy-N-phenylbenzamide, and t-butylbenzamido methylhydroxybenzamide.

Description

Composition for external use containing stable benzamide compounds obtained by controlling pH of the composition, and method for stabilizing the benzamide compounds}

The present invention relates to an external preparation composition for skin and a method for stabilizing the benzamide compound containing the stabilized benzamide compound as an active ingredient, and more particularly, by adjusting the pH range of the composition to pH 5 or less. It relates to a topical skin composition wherein the benzamide) compound is stably present in the composition and a method for stabilizing the benzamide compound thereof.

Various active ingredients of the cosmetic composition show excellent effects such as skin wrinkle improvement, whitening, antioxidant, and sunscreen, but due to the stability problem, the content decreases according to external stimuli such as temperature, moisture, and air, and thus the efficacy decreases. There is a limit to practical applications. Recently, studies to stabilize the active ingredients are actively underway.

Benzamide compounds used as active ingredients in external skin composition include resvera-A (3,5-Dihydroxy-N- (4-hydroxyphenyl) benzamide) and N-phenylbenzamide (N). -Phenylbenzamide, t-butylbenzamido hydroxybenzamide, 2-hydroxy-N-phenylbenzamide, N-phenylbenzamide derivative (N- phenylbenzamide derivatives) or t-butylbenzamido methylhydroxybenzamide. Among these, t-butylbenzamido hydroxybenzamide and t-butylbenzamido methylhydroxybenzamide are collagen generating effect and collagenase, an enzyme that degrades collagen. It has an effect of inhibiting expression, having an effect of inhibiting expression of elastease, an enzyme that degrades elastin, and thus can be used in cosmetic compositions for elasticity improvement. N-phenylbenzamide and its derivatives are also known to have bactericidal effects.

In particular, Resvera-A of Formula 1 is a mimic compound of trans-Resveratrol, which is effective in preventing heart disease and cancer by inhibiting platelet coagulation, preventing oxidation of lipid proteins, and reducing fatty acids. It is known to have effects such as wrinkle improvement, whitening, antioxidant, anti aging, anti inflammatory and anti stimulation.

Benzamide compounds are generally prepared by reacting benzoic acid with amine in the presence of methanesulfonyl chloride, and various benzamide compounds may be produced depending on groups substituted with benzoic acid and amine. It exists.

However, it is observed that the content of the benzamide compound decreases with time in the cosmetic composition, and it is necessary to secure a composition containing the stabilized active ingredient by identifying the cause of destabilization of the benzamide compound in the cosmetic composition.

In order to solve the above problems, the inventors have found that benzamide compounds such as Resvera-A, N-phenylbenzamide or t-butylbenzamido hydroxybenzamide have a change in structure depending on pH. This was confirmed through the peak pattern of MS, which set an optimal pH condition in which the benzamide structure could be stably present without change.

Therefore, an object of the present invention is to provide a topical composition for external skin containing a benzamide compound which is maintained in stability and efficacy by adjusting the pH of the composition to the optimum pH conditions. It is also an object of the present invention to provide a method for stabilizing the benzamide compound.

In order to achieve the above object, the present invention provides a topical skin composition containing a benzamide (benzamide) compound as an active ingredient, the pH range of the composition is characterized in that the pH 5 or less.

In the external preparation composition for skin of the present invention, the benzamide compound is characterized in that the substituent is present in the composition without degradation, and the benzamide compound is resvera-A (3,5). -Dihydroxy-N- (4-hydroxyphenyl) benzamide), N-Phenylbenzamide, t-butylbenzamido hydroxybenzamide, 2-hydroxy-N-phenyl Benzamide (2-hydroxy-N-phenylbenzamide), (N-phenylbenzamide derivatives) and t-butylbenzamido methylhydroxybenzamide (t-butylbenzamido methylhydroxybenzamide).

In the external preparation composition for skin of the present invention, the pH range is characterized in that the pH 3 ~ 5, the pH range is characterized by being adjusted with a phosphate buffer solution of lactic acid, salicylic acid, glycolic acid or pH 5 do.

In the external composition for skin composition of the present invention, the composition is characterized in that for improving wrinkles, the composition is characterized in that the cosmetic composition, the composition has a formulation of softening lotion, nourishing lotion, essence, lotion, emulsion or cream It is characterized by.

The present invention is a method for stabilizing a benzamide compound in an external composition for skin containing a benzamide compound as an active ingredient, wherein the pH range of the composition is adjusted to 5 or less by adding a pH adjusting agent to the composition. It provides a benzamide compound stabilization method in the external composition for skin.

In the benzamide compound stabilization method of the present invention, the benzamide compound is Resvera-A (3,5-Dihydroxy-N- (4-hydroxyphenyl) benzamide), N-phenylbenzamide (N-Phenylbenzamide), t- T-butylbenzamido hydroxybenzamide, 2-hydroxy-N-phenylbenzamide, (N-phenylbenzamide derivatives) and t-butylbenzamido methyl hydroxy It is characterized in that it is selected from the group consisting of hydroxybenzamide (t-butylbenzamido methylhydroxybenzamide).

In the benzamide compound stabilization method of the present invention, the pH adjusting agent is characterized in that the phosphate buffer solution of lactic acid, salicylic acid, glycolic acid or pH 5, the pH range is characterized in that pH 3 ~ 5. .

By setting the optimum pH range (pH 3.5-5) through the present invention, benzamide compounds such as resvera-A and N-phenylbenzamide or t-butylbenzamido hydroxybenzamide in the composition can be changed without structural changes. The external preparation composition for skin contained in the stabilized state can be provided. The external preparation composition for skin of the present invention may exist in cosmetic formulations of various compositions, and thus will be effectively applied to similar fields in the future.

The inventors have confirmed that the benzamide compounds, such as Resvera-A, N-phenylbenzamide or t-butylbenzamido hydroxybenzamide, change in pH depending on the peak pattern of HPLC and LC MS / MS. It was. That is, the benzamide compound has a pKa value in the range of 7 to 14, and the benzamide compound is dehydrotonated at a pH (pH 5 to 14) that is within the range of ± 2 than the pKa. Increased reactivity with the compound may result in degradation of the benzamide or formation of new compounds.

As a result, the benzamide compound cannot be stably present in a neutral environment or the like, and the benzamide compound can be formed only when the pH of the skin external preparation composition is adjusted to 3.5 to 5 or less, in which the dehydrogenation reaction of the benzamide compound does not occur. All have been found to be stable.

Hereinafter, the present invention will be described in more detail with reference to the following specific examples.

Experimental Example 1: Analysis of Stability of Resvera-A According to Various Conditions

In the present invention, as a representative benzamide compound among various benzamide compounds, the following experiment was performed using Resvera-A having the efficacy as described above.

First, an experiment was performed to compare the stability of various components of the Resvera-A raw material and the cosmetic composition containing 0.3% thereof using HPLC.

1. Comparison of Stability of Resvera-A Raw Materials

HPLC conditions are shown in Table 1 below. Figure 1 shows a high performance liquid chromatograph (HPLC) chromatogram of Resvera-A, where peak retention time (10.700 minutes), peak tailing and peak shape (height / width) of Resvera-A are suitable for quantitative analysis. It was confirmed.

Mobile phase Water / acetonitrile = 80/20 Extraction solvent Methanol column C18 (4.6 x 250 mm) Column temperature 25 ℃ Detector UV (280 nm) Sample temperature 25 ℃ flux 1.0ml / min Injection volume 20ul

In order to compare the stability of Resvera-A raw materials under various conditions, the change of content was measured over time while storing Resvera-A under 4 different conditions (light, temperature, oxidation, pH) for 4 weeks. . The change in content was calculated as {(content measured over time / initial content) x 100}. Resvera-A was used as a 1% Resvera-A sample solution prepared by adding Resvera-A to methanol, and pH conditions were prepared using lactic acid (α-hydroxy acid, AHA) and potassium hydroxide. pH was adjusted to the sample solution in the range of 2 ~ 10. The measurement results are shown in FIG.

As a result, it was confirmed that Resvera-A had a large change in stability depending on pH conditions. In particular, it was confirmed that the change over time was significantly greater than pH 5.

2. Comparative Experiment of Stability of Resvera-A According to pH in Cosmetic Composition

Based on the results of the experiment, in order to determine the change in stability according to the pH conditions of the Resvera-A in the emulsion containing the Resvera-A 0.3%, 4 weeks after adjusting the pH in the emulsion to 2 ~ 9 range The change over time was measured while storing. The pH control in the emulsion was controlled by slowly dropping lactic acid and potassium hydroxide into the formulation in an equivalent ratio. The measurement results are shown in FIG.

The results of the experiments show that the stability of the Resvera-A raw material is stable at pH 5 or less without change with time, but unstable at pH 5 or higher.

Thus, LC MS / MS was used to confirm the mechanism of structural change of Resvera-A above pH 5.

Experimental Example 2: Structure Analysis of Resvera-A According to pH

1.LC MS / MS

After preparing 1% Resvera-A sample solution using methanol, the sample solution was prepared in the range of pH 2-11 using phosphoric acid and triethylamine, and stored at room temperature for 1 week, followed by ESI- Measured in mode. The measurement results are shown in FIGS. 4 and 5.

As a result, as the pH was increased, the [M-H] 153 peak gradually increased, and below pH 5, the [M-H] 153 peak was not detected. The peak of [MH] 153 is 3,5-dihydroxy benzamide, which is degraded in Resvera-A, resulting in a drop in phenol as shown in FIG. It is generated as it goes. That is, it was confirmed that at pH 5 or less, Resvera-A did not decompose and exist stably.

Example 1 Preparation of Resvera-A Containing Lotion

Resvera-A containing lotions were prepared to examine the stabilizing effects in emulsion formulations. To prepare a composition of Table 2, each oil phase and water phase was completely dissolved at 70 ℃ and emulsified at 7,000 rpm for 5 minutes to prepare a lotion in the form of an opaque gel. The pH was adjusted by dropwise adding lactic acid (α-hydroxy acid, AHA) in equivalent ratio to adjust the pH to approximately 3.5 (Example 1a) and 5 (Example 1b).

ingredient Content (% by weight) Stearic acid 2 Cetyl alcohol 2 Lanolin alcohol 2 Liquid paraffin 7 Cyclomethicone 5 Polyoxyethylene monooleic acid ester 2 Preservatives, Antioxidants Quantity glycerin 3 Propylene glycol 5 Triethylamine One Resvera-A 0.3 Sodium Polyacrylate 0.15 Purified water to 100

Comparative Example 1: Preparation of Resvera-A Containing Lotion at pH 7

A lotion was prepared in the same composition as in Example 1 except that the pH was adjusted to approximately 7 using potassium hydroxide.

Test Example 1: Stability Test According to pH

In order to confirm the stability of the Resvera-A in the lotion prepared according to Example 1 and Comparative Example 1, after storing the prepared sample in a 40 ℃ oven for a certain period of time the residual Resvera-A amount by using liquid chromatography Was measured. The results are shown in Table 3 below.

Formulation Initial concentration retention rate (%) Immediately after manufacture 1 week later after 2 weeks 3 weeks later 4 weeks later Example 1a (pH 3.6) 100 100 100 100 100 Example 1b (pH 4.9) 100 100 100 100 100 Comparative Example 1 (pH 6.8) 100 95 93 89 85

As can be seen in Table 3, the Resvera-A is greatly affected by the pH of the formulation to maintain the initial concentration of the Resvera-A below pH 5, while the initial concentration retention of the Resvera-A above pH 5 is Very low.

Example 2 Preparation of Resvera-A-containing Skin

Resvera-A containing skin was prepared to examine the stabilizing effect in solubilizing formulations such as skins. To prepare a skin in the form of a transparent gel in the composition of Table 4. The pH was adjusted by dropwise adding lactic acid (α-hydroxy acid, AHA) in an equivalent ratio to adjust the pH to approximately 3.5 (Example 2a) and 5 (Example 2b). The viscosity of the formulation was about 4,000 cps as measured at 12 ° C. at 30 ° C. using Brookfield (LVDVII +).

ingredient Content (% by weight) glycerin 5 Propylene glycol 4 Resvera-A 0.3 ethanol 10 Sodium Polyacrylate 0.5 antiseptic Quantity Purified water to 100

Comparative Example 2: Preparation of Resvera-A-containing Skin at pH 7

A skin was prepared in the same composition as in Example 2 except that the pH was adjusted to approximately 7 using potassium hydroxide.

Test Example 2: Stability Test According to pH

In order to confirm the stability of the Resvera-A in the skin prepared according to Example 2 and Comparative Example 2, the prepared sample was stored in an oven at 40 ° C. for a certain time, and then liquid phase chromatography was used to determine the remaining Resvera-A. The amount was measured. The results are shown in Table 5 below.

Formulation Initial concentration retention rate (%) Immediately after manufacture 1 week later after 2 weeks 3 weeks later 4 weeks later Example 2a (pH 3.4) 100 100 100 100 100 Example 2b (pH 5.1) 100 100 100 99 99 Comparative Example 2 (pH 7.2) 100 95 91 85 81

As can be seen in Table 5, the resvera-A is greatly affected by the pH of the formulation to maintain the initial concentration of the resvera-A below pH 5, while the initial concentration retention of the resvera-A above pH 5 is Very low.

Example 3: Manufacture of Resvera-A Cream

Resvera-A containing cream was prepared to examine the stabilizing effect in the emulsion formulation. To prepare a cream of the composition of Table 6, each oil phase and water phase was completely dissolved at 70 ℃ and emulsified at 7,000 rpm for 5 minutes. The pH was adjusted by dropwise adding lactic acid (α-hydroxy acid, AHA) in equivalent ratio to adjust the pH to approximately 3.5 (Example 3a) and 5 (Example 3b).

ingredient Content (% by weight) Beads wax 2 Stearyl alcohol 5 Stearic acid 8 Squalane 10 Propylene Glycol Monostearate 3 Polyoxyethylene cetyl ether One Preservatives and Antioxidants Quantity Propylene glycol 8 Triethylamine One Resvera-A 0.3 Purified water to 100

Comparative Example 3: Preparation of Resvera-A Cream with pH 7

Cream was prepared in the same composition as in Example 3 except that the pH was adjusted to approximately 7 using potassium hydroxide.

Test Example 3: Stability Test According to pH

In order to confirm the stability of the Resvera-A in the cream prepared according to Example 3 and Comparative Example 3, after storing the prepared sample in a 40 ℃ oven for a period of time using the residual chromatography amount of Resvera-A Was measured. The results are shown in Table 7 below.

Formulation Initial concentration retention rate (%) Immediately after manufacture 1 week later after 2 weeks 3 weeks later 4 weeks later Example 3a (pH 3.5) 100 100 100 100 100 Example 3b (pH 4.8) 100 100 100 100 100 Comparative Example 3 (pH 6.8) 100 96 93 91 87

As can be seen in Table 7, Resvera-A is greatly affected by the pH of the formulation to maintain the initial concentration of Resvera-A below pH 5, while the initial concentration retention of Resvera-A above pH 5 is Very low.

Example 4: Preparation of N-phenylbenzamide-containing lotion

N-phenylbenzamide-containing lotions were prepared to examine the stabilizing effects in emulsion formulations. To prepare a composition of Table 8, each oil phase and water phase was completely dissolved at 70 ℃ and emulsified at 7,000 rpm for 5 minutes to prepare a lotion in the form of an opaque gel. pH adjustment was performed by dropwise adding lactic acid (α-hydroxy acid, AHA) in equivalent ratio to adjust the pH to approximately 3.5 (Example 4a) and 5 (Example 4b).

ingredient Content (% by weight) Stearic acid 2 Cetyl alcohol 2 Lanolin alcohol 2 Liquid paraffin 7 Cyclomethicone 5 Polyoxyethylene monooleic acid ester 2 Preservatives, Antioxidants Quantity glycerin 3 Propylene glycol 5 Triethylamine One N-phenylbenzamide 0.3 Sodium Polyacrylate 0.15 Purified water to 100

Comparative Example 4: Preparation of N-phenylbenzamide-containing lotion at pH 7

A lotion was prepared in the same composition as in Example 4 except that the pH was adjusted to approximately 7 using potassium hydroxide.

Test Example 4: Stability Test According to pH

In order to confirm the stability of N-phenylbenzamide in the lotion prepared according to Example 4 and Comparative Example 4, the prepared sample was stored in an oven at 40 ° C. for a predetermined time, and then residual N-phenylbenz was used by liquid chromatography. The amount of amide was measured. The results are shown in Table 9 below.

Formulation Initial concentration retention rate (%) Immediately after manufacture 1 week later after 2 weeks 3 weeks later 4 weeks later Example 4a (pH 3.8) 100 100 100 100 100 Example 4b (pH 4.9) 100 100 100 100 100 Comparative Example 4 (pH 6.7) 100 95 91 87 83

As can be seen in Table 9, N-phenylbenzamide is greatly affected by the pH of the formulation to maintain the initial concentration of N-phenylbenzamide below pH 5, while the initial concentration of N-phenylbenzamide above pH 5 The concentration retention was very low.

Example 5 Preparation of N-phenylbenzamide-Containing Skin

N-phenylbenzamide containing skin was prepared to examine the stabilizing effect in the solubilized formulation. To prepare a skin in the form of a transparent gel in the composition of Table 10. The pH was adjusted by dropwise adding lactic acid (α-hydroxy acid, AHA) in equivalent ratio to adjust the pH to approximately 3.5 (Example 5a) and 5 (Example 5b). The viscosity of the formulation was about 4,000 cps as measured at 12 ° C. at 30 ° C. using Brookfield (LVDVII +).

ingredient Content (% by weight) glycerin 5 Propylene glycol 4 N-phenylbenzamide 0.3 ethanol 10 Sodium Polyacrylate 0.5 antiseptic Quantity Purified water to 100

Comparative Example 5: Preparation of N-phenylbenzamide-Containing Skin at pH 7

Skin was prepared in the same composition as in Example 5 except that the pH was adjusted to approximately 7 using potassium hydroxide.

Test Example 5: Stability Test According to pH

In order to confirm the stability of N-phenylbenzamide in the skin prepared according to Example 5 and Comparative Example 5, the prepared sample was stored in an oven at 40 ° C. for a certain time, and then residual N-phenylbenz was used by liquid chromatography. The amount of amide was measured. The results are shown in Table 11 below.

Formulation Initial concentration retention rate (%) After manufacturing 1 week later after 2 weeks 3 weeks later 4 weeks later Example 5a (pH 3.3) 100 100 100 100 100 Example 5b (pH 5.2) 100 100 100 100 100 Comparative Example 5 (pH 7.1) 100 95 91 86 81

As can be seen in Table 11, N-phenylbenzamide is greatly affected by the pH of the formulation to maintain the initial concentration of N-phenylbenzamide below pH 5, while the initial concentration of N-phenylbenzamide above pH 5 The retention rate is very low.

Example 6: Preparation of N-phenylbenzamide-containing cream

N-phenylbenzamide containing creams were prepared to examine the stabilizing effects in emulsion formulations. To prepare a composition of Table 12, each of the oil phase and water phase was completely dissolved at 70 ℃ and emulsified at 7,000 rpm for 5 minutes to prepare a cream. The pH was adjusted by dropwise adding lactic acid (α-hydroxy acid, AHA) in equivalent ratio to adjust the pH to approximately 3.5 (Example 6a) and 5 (Example 6b).

ingredient Content (% by weight) Beads wax 2 Stearyl alcohol 5 Stearic acid 8 Squalane 10 Propylene Glycol Monostearate 3 Polyoxyethylene cetyl ether One Preservatives and Antioxidants Quantity Propylene glycol 8 Triethylamine One N-phenylbenzamide 0.3 Purified water  to 100

Comparative Example 6: Preparation of N-phenylbenzamide-containing cream of pH 7

Cream was prepared in the same composition as in Example 6 except that the pH was adjusted to approximately 7 using potassium hydroxide.

Test Example 6: Stability Test According to pH

In order to confirm the stability of the N-phenylbenzamide in the cream prepared according to Example 6 and Comparative Example 6, the prepared sample was stored in an oven at 40 ° C. for a certain time, and then residual N-phenylbenz was used by liquid chromatography. The amount of amide was measured. The results are shown in Table 13 below.

Formulation Initial concentration retention rate (%) After manufacturing 1 week later after 2 weeks 3 weeks later 4 weeks later Example 6a (pH 3.4) 100 100 100 100 100 Example 6b (pH 5.0) 100 100 100 100 100 Comparative Example 6 (pH 7.0) 100 95 90 86 81

As can be seen in Table 13, N-phenylbenzamide is greatly affected by the pH of the formulation to maintain the initial concentration of N-phenylbenzamide below pH 5, while the initial concentration of N-phenylbenzamide above pH 5 The retention rate is very low.

Example 7: Preparation of t-butylbenzamido hydroxybenzamide-containing lotion

A t-butylbenzamido hydroxybenzamide containing lotion was prepared to examine the stabilizing effect in the emulsion formulation. To prepare a composition of Table 14, each oil phase and water phase was completely dissolved at 70 ℃ and emulsified at 7,000 rpm for 5 minutes to prepare a lotion in the form of an opaque gel. The pH was adjusted by dropwise adding lactic acid (α-hydroxy acid, AHA) in equivalent ratio to adjust the pH to approximately 3.5 (Example 7a) and 5 (Example 7b).

ingredient Content (% by weight) Stearic acid 2 Cetyl alcohol 2 Lanolin alcohol 2 Liquid paraffin 7 Cyclomethicone 5 Polyoxyethylene monooleic acid ester 2 Preservatives, Antioxidants Quantity glycerin 3 Propylene glycol 5 Triethylamine One t-butylbenzamido hydroxybenzamide 0.3 Sodium Polyacrylate 0.15 Purified water to 100

Comparative Example 7: Preparation of t-butylbenzamido hydroxybenzamide-containing lotion at pH 7

A lotion was prepared in the same composition as in Example 7, except that the pH was adjusted to approximately 7 using potassium hydroxide.

Test Example 7: Stability Test According to pH

In order to confirm the stability of t-butylbenzamido hydroxybenzamide in the lotions prepared according to Example 7 and Comparative Example 7, the prepared samples were stored in an oven at 40 ° C. for a period of time, and then liquid phase chromatography was used. Residual t-butylbenzamido hydroxybenzamide amount was measured. The results are shown in Table 15 below.

Formulation Initial concentration retention rate (%) Immediately after manufacture 1 week later after 2 weeks 3 weeks later 4 weeks later Example 7a (pH 3.8) 100 100 100 100 100 Example 7b (pH 4.9) 100 100 100 100 100 Comparative Example 7 (pH 6.7) 100 95 91 87 83

As can be seen in Table 15, t-butylbenzamido hydroxybenzamide is greatly affected by the pH of the formulation, pH below 5, while t-butylbenzamido hydroxybenzamide maintains the initial concentration, while pH Above 5, the initial concentration retention of t-butylbenzamido hydroxybenzamide was very low.

Example 8: Preparation of t-butylbenzamido hydroxybenzamide-containing skin

A t-butylbenzamido hydroxybenzamide containing skin was prepared to examine the stabilizing effect in the solubilized formulation. To prepare a skin in the form of a transparent gel in the composition of Table 16. The pH was adjusted by dropwise adding lactic acid (α-hydroxy acid, AHA) in equivalent ratio to adjust the pH to approximately 3.5 (Example 8a) and 5 (Example 8b). The viscosity of the formulation was about 4,000 cps as measured at 12 ° C. at 30 ° C. using Brookfield (LVDVII +).

ingredient Content (% by weight) glycerin 5 Propylene glycol 4 t-butylbenzamido hydroxybenzamide 0.3 ethanol 10 Sodium Polyacrylate 0.5 antiseptic Quantity Purified water to 100

Comparative Example 8: Preparation of skin containing t-butylbenzamido hydroxybenzamide at pH 7

Skin was prepared in the same composition as in Example 8 except that the pH was adjusted to approximately 7 using potassium hydroxide.

Test Example 8: Stability Test According to pH

In order to confirm the stability of t-butylbenzamido hydroxybenzamide in the skin prepared according to Example 8 and Comparative Example 8, the prepared sample was stored in an oven at 40 ° C. for a predetermined time, and then liquid phase chromatography was used. The amount of remaining t-butylbenzamido hydroxybenzamide was measured. The results are shown in Table 17 below.

Formulation Initial concentration retention rate (%) After manufacturing 1 week later after 2 weeks 3 weeks later 4 weeks later Example 8a (pH 3.3) 100 100 100 100 100 Example 8b (pH 5.2) 100 100 100 100 100 Comparative Example 8 (pH 7.1) 100 95 91 86 81

As can be seen in Table 17, the pH of the formulation of t-butylbenzamido hydroxybenzamide is greatly affected by the pH of the formulation of t-butylbenzamido hydroxybenzamide below pH 5, while pH Above 5, the initial concentration retention of t-butylbenzamido hydroxybenzamide was very low.

<Example 9: t-butylbenzamido hydroxybenzamide-containing cream preparation>

A t-butylbenzamido hydroxybenzamide containing cream was prepared to examine the stabilizing effect in the emulsion formulation. Prepared in the composition shown in Table 18, each oil and water phase was completely dissolved at 70 ℃ and emulsified at 7,000 rpm for 5 minutes to prepare a cream. pH adjustment was performed by dropwise adding lactic acid (α-hydroxy acid, AHA) in equivalent ratio to adjust the pH to approximately 3.5 (Example 9a) and 5 (Example 9b).

ingredient Content (% by weight) Beads wax 2 Stearyl alcohol 5 Stearic acid 8 Squalane 10 Propylene Glycol Monostearate 3 Polyoxyethylene cetyl ether One Preservatives and Antioxidants Quantity Propylene glycol 8 Triethylamine One t-butylbenzamido hydroxybenzamide 0.3 Purified water  to 100

Comparative Example 9: Preparation of cream containing t-butylbenzamido hydroxybenzamide at pH 7

Cream was prepared in the same composition as in Example 9 except that the pH was adjusted to approximately 7 using potassium hydroxide.

Test Example 9: Stability Test According to pH

In order to confirm the stability of t-butylbenzamido hydroxybenzamide in the cream prepared according to Example 9 and Comparative Example 9, the prepared sample was stored in an oven at 40 ° C. for a certain time, and then liquid phase chromatography was used. Residual t-butylbenzamido hydroxybenzamide amount was measured. The results are shown in Table 19 below.

Formulation Initial concentration retention rate (%) After manufacturing 1 week later after 2 weeks 3 weeks later 4 weeks later Example 9a (pH 3.4) 100 100 100 100 100 Example 9b (pH 5.0) 100 100 100 100 100 Comparative Example 9 (pH 7.0) 100 95 90 86 81

As can be seen in Table 19, the pH of the formulation of t-butylbenzamido hydroxybenzamide is greatly affected so that the pH of the t-butylbenzamido hydroxybenzamide is maintained below pH 5, while the pH Above 5, the initial concentration retention of t-butylbenzamido hydroxybenzamide was very low.

Example 10 Preparation of 2-hydroxy-N-phenylbenzamide-containing lotion

A 2-hydroxy-N-phenylbenzamide containing lotion was prepared to examine the stabilizing effect in the emulsion formulation. To prepare a composition of Table 20, each oil phase and water phase was completely dissolved at 70 ℃ and emulsified at 7,000 rpm for 5 minutes to prepare a lotion in the form of an opaque gel. The pH was adjusted by dropwise adding lactic acid (α-hydroxy acid, AHA) in equivalent ratio to adjust the pH to approximately 3.5 (Example 10a) and 5 (Example 10b).

ingredient Content (% by weight) Stearic acid 2 Cetyl alcohol 2 Lanolin alcohol 2 Liquid paraffin 7 Cyclomethicone 5 Polyoxyethylene monooleic acid ester 2 Preservatives, Antioxidants Quantity glycerin 3 Propylene glycol 5 Triethylamine One 2-hydroxy-N-phenylbenzamide 0.3 Sodium Polyacrylate 0.15 Purified water to 100

Comparative Example 10 Preparation of 2-hydroxy-N-phenylbenzamide-containing lotion at pH 7

A lotion was prepared in the same composition as in Example 10 except that the pH was adjusted to approximately 7 using potassium hydroxide.

Test Example 10: Stability Test According to pH

In order to confirm the stability of 2-hydroxy-N-phenylbenzamide in the lotion prepared according to Example 10 and Comparative Example 10, the prepared sample was stored in an oven at 40 ° C. for a predetermined time, and then liquid phase chromatography was used. The remaining amount of 2-hydroxy-N-phenylbenzamide was measured. The results are shown in Table 21 below.

Formulation Initial concentration retention rate (%) Immediately after manufacture 1 week later after 2 weeks 3 weeks later 4 weeks later Example 10a (pH 3.8) 100 100 100 100 100 Example 10b (pH 4.9) 100 100 100 100 100 Comparative Example 10 (pH 6.7) 100 95 91 87 83

As can be seen from Table 21, the 2-hydroxy-N-phenylbenzamide is greatly affected by the pH of the formulation to maintain the initial concentration of 2-hydroxy-N-phenylbenzamide below pH 5, while the pH Above 5, the initial concentration retention of 2-hydroxy-N-phenylbenzamide was very low.

Example 11: Preparation of 2-hydroxy-N-phenylbenzamide-containing skin

2-hydroxy-N-phenylbenzamide containing skin was prepared to examine the stabilizing effect in the solubilized formulation. To prepare a skin in the form of a transparent gel in the composition of Table 22. The pH was adjusted by dropwise adding lactic acid (α-hydroxy acid, AHA) in an equivalent ratio to adjust the pH to approximately 3.5 (Example 11a) and 5 (Example 11b). The viscosity of the formulation was about 4,000 cps as measured at 12 ° C. at 30 ° C. using Brookfield (LVDVII +).

ingredient Content (% by weight) glycerin 5 Propylene glycol 4 2-hydroxy-N-phenylbenzamide 0.3 ethanol 10 Sodium Polyacrylate 0.5 antiseptic Quantity Purified water to 100

Comparative Example 11: Preparation of 2-hydroxy-N-phenylbenzamide-containing skin at pH 7

A skin was prepared in the same composition as in Example 11 except for adjusting the pH to approximately 7 using potassium hydroxide.

Test Example 11: Stability Test According to pH

In order to confirm the stability of 2-hydroxy-N-phenylbenzamide in the skin prepared according to Example 11 and Comparative Example 11, the prepared sample was stored in an oven at 40 ° C. for a predetermined time, and then liquid phase chromatography was used. The amount of remaining 2-hydroxy-N-phenylbenzamide was measured. The results are shown in Table 23 below.

Formulation Initial concentration retention rate (%) After manufacturing 1 week later after 2 weeks 3 weeks later 4 weeks later Example 11a (pH 3.3) 100 100 100 100 100 Example 11b (pH 5.2) 100 100 100 100 100 Comparative Example 11 (pH 7.1) 100 95 91 86 81

As can be seen in Table 23, the pH of the formulation of 2-hydroxy-N-phenylbenzamide is greatly influenced to maintain the initial concentration of 2-hydroxy-N-phenylbenzamide below pH 5, while Above 5, the initial concentration retention of 2-hydroxy-N-phenylbenzamide was very low.

<Example 12: Preparation of 2-hydroxy-N-phenylbenzamide containing cream>

2-hydroxy-N-phenylbenzamide containing cream was prepared to examine the stabilizing effect in the emulsion formulation. To prepare a cream of the composition of Table 24, each oil phase and water phase was completely dissolved at 70 ℃ and emulsified at 7,000 rpm for 5 minutes. The pH was adjusted by dropwise adding lactic acid (α-hydroxy acid, AHA) in equivalent ratio to adjust the pH to approximately 3.5 (Example 12a) and 5 (Example 12b).

ingredient Content (% by weight) Beads wax 2 Stearyl alcohol 5 Stearic acid 8 Squalane 10 Propylene Glycol Monostearate 3 Polyoxyethylene cetyl ether One Preservatives and Antioxidants Quantity Propylene glycol 8 Triethylamine One 2-hydroxy-N-phenylbenzamide 0.3 Purified water  to 100

Comparative Example 12 Preparation of 2-hydroxy-N-phenylbenzamide-Containing Cream of pH 7

Cream was prepared in the same composition as in Example 12 except that the pH was adjusted to approximately 7 using potassium hydroxide.

Test Example 12: Stability Test According to pH

In order to confirm the stability of 2-hydroxy-N-phenylbenzamide in the cream prepared according to Example 12 and Comparative Example 12, the prepared sample was stored in an oven at 40 ° C. for a predetermined time, and then liquid phase chromatography was used. The remaining amount of 2-hydroxy-N-phenylbenzamide was measured. The results are shown in Table 25 below.

Formulation Initial concentration retention rate (%) After manufacturing 1 week later after 2 weeks 3 weeks later 4 weeks later Example 12a (pH 3.4) 100 100 100 100 100 Example 12b (pH 5.0) 100 100 100 100 100 Comparative Example 12 (pH 7.0) 100 95 90 86 81

As can be seen in Table 25, the pH of the formulation of 2-hydroxy-N-phenylbenzamide is greatly influenced to maintain the initial concentration of 2-hydroxy-N-phenylbenzamide below pH 5, while the pH Above 5, the initial concentration retention of 2-hydroxy-N-phenylbenzamide was very low.

Example 13: Preparation of t-butylbenzamido methylhydroxybenzamide-containing lotion

A t-butylbenzamido methylhydroxybenzamide containing lotion was prepared to examine the stabilizing effect in the emulsion formulation. To prepare a composition of Table 26, each oil phase and water phase was completely dissolved at 70 ℃ and emulsified at 7,000 rpm for 5 minutes to prepare a lotion in the form of an opaque gel. The pH was adjusted by dropwise adding lactic acid (α-hydroxy acid, AHA) in equivalent ratio to adjust the pH to approximately 3.5 (Example 13a) and 5 (Example 13b).

ingredient Content (% by weight) Stearic acid 2 Cetyl alcohol 2 Lanolin alcohol 2 Liquid paraffin 7 Cyclomethicone 5 Polyoxyethylene monooleic acid ester 2 Preservatives, Antioxidants Quantity glycerin 3 Propylene glycol 5 Triethylamine One t-butylbenzamido methylhydroxybenzamide 0.3 Sodium Polyacrylate 0.15 Purified water to 100

Comparative Example 13: Preparation of t-butylbenzamido methylhydroxybenzamide-containing lotion at pH 7

A lotion was prepared in the same composition as in Example 13 except that the pH was adjusted to approximately 7 using potassium hydroxide.

Test Example 13: Stability Test According to pH

In order to confirm the stability of t-butylbenzamido methylhydroxybenzamide in the lotion prepared according to Example 13 and Comparative Example 13, the prepared sample was stored in an oven at 40 ° C. for a predetermined time, and then liquid phase chromatography was used. Residual t-butylbenzamido methylhydroxybenzamide was measured. The results are shown in Table 27 below.

Formulation Initial concentration retention rate (%) Immediately after manufacture 1 week later after 2 weeks 3 weeks later 4 weeks later Example 13a (pH 3.8) 100 100 100 100 100 Example 13b (pH 4.9) 100 100 100 100 100 Comparative Example 13 (pH 6.7) 100 95 91 87 83

As can be seen in Table 27, t-butylbenzamido methylhydroxybenzamide is significantly affected by the pH of the formulation, so that at pH 5 or lower, t-butylbenzamido maintains the initial concentration of methylhydroxybenzamide. and pH 5 or more, the initial concentration retention of t-butylbenzamido methylhydroxybenzamide was very low.

<Example 14: t-butylbenzamido methylhydroxybenzamide-containing skin preparation>

A t-butylbenzamido methylhydroxybenzamide containing skin was prepared to examine the stabilizing effect in the solubilized formulation. To prepare a skin in the form of a transparent gel in the composition of Table 28. The pH was adjusted by dropwise adding lactic acid (α-hydroxy acid, AHA) in equivalent ratio to adjust the pH to approximately 3.5 (Example 14a) and 5 (Example 14b). The viscosity of the formulation was about 4,000 cps as measured at 12 ° C. at 30 ° C. using Brookfield (LVDVII +).

ingredient Content (% by weight) glycerin 5 Propylene glycol 4 t-butylbenzamido methylhydroxybenzamide 0.3 ethanol 10 Sodium Polyacrylate 0.5 antiseptic Quantity Purified water to 100

Comparative Example 14 Preparation of Skin Containing t-Butylbenzamido Methylhydroxybenzamide at pH 7

A skin was prepared in the same composition as in Example 14 except that the pH was adjusted to approximately 7 using potassium hydroxide.

Test Example 14: Stability Test According to pH

In order to confirm the stability of t-butylbenzamido methylhydroxybenzamide in the skin prepared according to Example 14 and Comparative Example 14, the prepared sample was stored in an oven at 40 ° C. for a predetermined time, and then liquid phase chromatography was used. The amount of residual t-butylbenzamido methylhydroxybenzamide was measured. The results are shown in Table 29 below.

Formulation Initial concentration retention rate (%) After manufacturing 1 week later after 2 weeks 3 weeks later 4 weeks later Example 14a (pH 3.3) 100 100 100 100 100 Example 14b (pH 5.2) 100 100 100 100 100 Comparative Example 14 (pH 7.1) 100 95 91 86 81

As can be seen in Table 29, t-butylbenzamido is greatly influenced by the pH of the formulation of methylhydroxybenzamide, and at pH 5 or lower, t-butylbenzamido maintains the initial concentration of methylhydroxybenzamide. and pH 5 or more, the initial concentration retention of t-butylbenzamido methylhydroxybenzamide was very low.

<Example 15: t-butylbenzamido methylhydroxybenzamide-containing cream preparation>

A t-butylbenzamido methylhydroxybenzamide containing cream was prepared to examine the stabilizing effect in the emulsion formulation. To prepare a cream of the composition of Table 30, each oil phase and water phase was completely dissolved at 70 ℃ and emulsified at 7,000 rpm for 5 minutes. pH adjustment was performed by dropwise adding lactic acid (α-hydroxy acid, AHA) in equivalent ratio to adjust the pH to approximately 3.5 (Example 15a) and 5 (Example 15b).

ingredient Content (% by weight) Beads wax 2 Stearyl alcohol 5 Stearic acid 8 Squalane 10 Propylene Glycol Monostearate 3 Polyoxyethylene cetyl ether One Preservatives and Antioxidants Quantity Propylene glycol 8 Triethylamine One t-butylbenzamido methylhydroxybenzamide 0.3 Purified water  to 100

<Comparative Example 15: Preparation of cream containing t-butylbenzamido methylhydroxybenzamide at pH 7>

Cream was prepared in the same composition as in Example 15 except that the pH was adjusted to approximately 7 using potassium hydroxide.

Test Example 15: Stability Test According to pH

In order to confirm the stability of t-butylbenzamido methylhydroxybenzamide in the cream prepared according to Example 15 and Comparative Example 15, the prepared sample was stored in an oven at 40 ° C. for a certain time, and then liquid phase chromatography was used. Residual t-butylbenzamido methylhydroxybenzamide was measured. The results are shown in Table 31 below.

Formulation Initial concentration retention rate (%) After manufacturing 1 week later after 2 weeks 3 weeks later 4 weeks later Example 15a (pH 3.4) 100 100 100 100 100 Example 15b (pH 5.0) 100 100 100 100 100 Comparative Example 15 (pH 7.0) 100 95 90 86 81

As can be seen in Table 31, t-butylbenzamido is greatly influenced by the pH of the formulation of methylhydroxybenzamide, and at pH 5 or lower, t-butylbenzamido maintains the initial concentration of methylhydroxybenzamide. and pH 5 or more, the initial concentration retention of t-butylbenzamido methylhydroxybenzamide was very low.

Example 16: Preparation of Resvera-A Cream Using Various pH Control Agents

In order to examine the stabilizing effect according to the type of pH regulator, a cream containing Resvera-A using various pH regulators was prepared. Prepared in the composition of Table 6, each oil phase and water phase was completely dissolved at 70 ℃, and emulsified at 7,000 rpm for 5 minutes to prepare a cream. The pH was adjusted to approximately 5 by dropwise adding lactic acid (Example 16a), salicylic acid (Example 16b), and glycolic acid (Example 16c) in an equivalent ratio, respectively. When the pH was adjusted with a phosphate buffer solution of pH 5 (Example 16d), a cream was prepared using a phosphate buffer solution instead of purified water in the composition of Table 6.

Experimental Example 16: Comparison of Resvera-A Stability According to Types of pH Control Agents

In order to confirm the stability of Resvera-A in various creams prepared according to Example 16, the prepared samples were stored in an oven at 40 ° C. for a period of time, and then liquid phase chromatography was used to determine the amount of Resvera-A. Measured. The results are shown in Table 32 below.

Formulation Initial concentration retention rate (%) Immediately after manufacture 1 week later after 2 weeks 3 weeks later 4 weeks later Example 16a 100 100 100 100 100 Example 16b 100 100 100 100 99 Example 16c 100 100 100 99 99 Example 16d 100 100 100 100 100

As can be seen in Table 32, Resvera-A maintains the initial concentration of the Resvera-A below pH 5 regardless of the type of pH regulator used in the formulation. Therefore, it can be seen that lactic acid, salicylic acid, glycolic acid or phosphate buffer solution may be used as a pH adjusting agent in a formulation containing resvera-A.

Example 17 Preparation of N-Phenylbenzamide-Containing Cream Using Various pH Control Agents

In order to examine the stabilizing effect according to the type of pH regulator, N-phenylbenzamide-containing cream using various pH regulators was prepared. It was prepared in the composition of Table 12, each oil phase and water phase was completely dissolved at 70 ℃, emulsified at 7,000 rpm for 5 minutes to prepare a cream. The pH was adjusted to approximately 5 by dropwise adding lactic acid (Example 17a), salicylic acid (Example 17b), and glycolic acid (Example 17c) in an equivalent ratio, respectively. When the pH was adjusted with a phosphate buffer solution of pH 5 (Example 17d), a cream was prepared using a phosphate buffer solution instead of purified water in the composition of Table 12.

<Test Example 17: Comparison of N-phenylbenzamide stability according to the pH regulator type>

In order to confirm the stability of N-phenylbenzamide in the various creams prepared according to Example 17, the prepared samples were stored in an oven at 40 ° C. for a period of time, and then liquid phase chromatography was used to determine the residual N-phenylbenzamide. The amount was measured. The results are shown in Table 33 below.

Formulation Initial concentration retention rate (%) Immediately after manufacture 1 week later after 2 weeks 3 weeks later 4 weeks later Example 17a 100 100 100 99 99 Example 17b 100 100 100 100 100 Example 17c 100 100 100 100 99 Example 17d 100 100 100 100 99

As can be seen in Table 33, N-phenylbenzamide maintains the initial concentration of N-phenylbenzamide at pH 5 or less regardless of the type of pH adjuster used in the formulation. Therefore, it can be seen that lactic acid, salicylic acid, glycolic acid or phosphate buffer solution may be used as a pH adjusting agent in a formulation containing N-phenylbenzamide.

<Example 18: Preparation of t-butylbenzamido hydroxybenzamide-containing cream using various pH adjusting agents>

In order to examine the stabilizing effect according to the type of pH regulator, t-butylbenzamido hydroxybenzamide-containing cream using various pH regulators was prepared. Prepared in the composition shown in Table 18, each oil phase and water phase was completely dissolved at 70 ℃, emulsified at 7,000 rpm for 5 minutes to prepare a cream. The pH was adjusted to approximately 5 by dropwise adding lactic acid (Example 18a), salicylic acid (Example 18b) and glycolic acid (Example 18c) in equivalent ratios, respectively. When the pH was adjusted with a phosphate buffer solution of pH 5 (Example 18d), a cream was prepared using a phosphate buffer solution instead of purified water in the composition of Table 18.

<Test Example 18: Comparison of t-butylbenzamido hydroxybenzamide stability according to the pH regulator type>

In order to confirm the stability of t-butylbenzamido hydroxybenzamide in the various creams prepared according to Example 18, the prepared sample was stored in a 40 ° C. oven for a period of time, and then liquid t was used by liquid chromatography. -Butylbenzamido hydroxybenzamide was measured. The results are shown in Table 34 below.

Formulation Initial concentration retention rate (%) Immediately after manufacture 1 week later after 2 weeks 3 weeks later 4 weeks later Example 18a 100 100 100 100 99 Example 18b 100 100 100 100 100 Example 18c 100 100 100 100 100 Example 18d 100 100 100 99 99

As can be seen in Table 34, t-butylbenzamido hydroxybenzamide maintains the initial concentration of t-butylbenzamido hydroxybenzamide below pH 5 regardless of the type of pH adjuster used in the formulation. have. Therefore, it can be seen that lactic acid, salicylic acid, glycolic acid or phosphate buffer solution may be used as a pH adjusting agent in a formulation containing t-butylbenzamido hydroxybenzamide.

<Example 19: Preparation of 2-hydroxy-N-phenylbenzamide containing cream using various pH adjusting agents>

In order to examine the stabilizing effect according to the type of pH adjusting agent, a cream containing 2-hydroxy-N-phenylbenzamide using various pH adjusting agents was prepared. It was prepared in the composition of Table 24, each oil phase and water phase was completely dissolved at 70 ℃, emulsified at 7,000 rpm for 5 minutes to prepare a cream. The pH was adjusted to approximately 5 by dropwise adding lactic acid (Example 19a), salicylic acid (Example 19b) and glycolic acid (Example 19c) in equivalent ratios, respectively. When the pH was adjusted with a phosphate buffer solution of pH 5 (Example 19d), a cream was prepared using a phosphate buffer solution instead of purified water in the composition of Table 24.

Test Example 19 Comparison of Stability of 2-Hydroxy-N-phenylbenzamide According to pH Adjuster Type

In order to confirm the stability of 2-hydroxy-N-phenylbenzamide in the various creams prepared according to Example 19, the prepared samples were stored in an oven at 40 ° C. for a period of time, The amount of -hydroxy-N-phenylbenzamide was measured. The results are shown in Table 35 below.

Formulation Initial concentration retention rate (%) Immediately after manufacture 1 week later after 2 weeks 3 weeks later 4 weeks later Example 19a 100 100 100 100 99 Example 19b 100 100 100 100 100 Example 19c 100 100 100 100 99 Example 19d 100 100 100 99 99

As can be seen in Table 35, 2-hydroxy-N-phenylbenzamide maintains the initial concentration of 2-hydroxy-N-phenylbenzamide below pH 5 regardless of the type of pH adjuster used in the formulation. have. Therefore, it can be seen that lactic acid, salicylic acid, glycolic acid or phosphate buffer solution may be used as a pH adjusting agent in the formulation containing 2-hydroxy-N-phenylbenzamide.

<Example 20: Preparation of t-butylbenzamido methylhydroxybenzamide-containing cream using various pH adjusting agents>

In order to examine the stabilizing effect according to the type of pH regulator, t-butylbenzamido methylhydroxybenzamide-containing cream using various pH regulators was prepared. It was prepared in the composition of Table 30, each oil phase and water phase was completely dissolved at 70 ℃, emulsified at 7,000rpm for 5 minutes to prepare a cream. The pH was adjusted to approximately 5 by dropwise adding lactic acid (Example 20a), salicylic acid (Example 20b), and glycolic acid (Example 20) in an equivalent ratio, respectively. When the pH was adjusted with a phosphate buffer solution of pH 5 (Example 20d), a cream was prepared using a phosphate buffer solution instead of purified water in the composition of Table 30.

<Test Example 20: Comparison of t-butylbenzamido methylhydroxybenzamide stability according to the pH regulator type>

In order to confirm the stability of t-butylbenzamido methylhydroxybenzamide in the various creams prepared according to Example 20, the prepared samples were stored in a 40 ° C. oven for a period of time, and then remaining using liquid chromatography. The amount of t-butylbenzamido methylhydroxybenzamide was measured. The results are shown in Table 36 below.

Formulation Initial concentration retention rate (%) Immediately after manufacture 1 week later after 2 weeks 3 weeks later 4 weeks later Example 20a 100 100 100 100 100 Example 20b 100 100 100 100 100 Example 20c 100 100 100 100 100 Example 20d 100 100 100 100 99

As can be seen from Table 36, t-butylbenzamido methylhydroxybenzamide is the initial concentration of t-butylbenzamido methylhydroxybenzamide below pH 5 regardless of the type of pH regulator used in the formulation. Keeping up. Therefore, it can be seen that lactic acid, salicylic acid, glycolic acid or phosphate buffer solution may be used as a pH adjusting agent in a formulation containing t-butylbenzamido methylhydroxybenzamide.

1 is a diagram showing an HPLC chromatogram of Resvera-A.

2 is a diagram showing the results of a comparative experiment of stability of the Resvera-A raw materials according to various conditions.

Figure 3 is a diagram showing the results of a comparative experiment of stability of the resvera-A in the cosmetic composition according to pH.

Figure 4 shows the LC MS / MS results for the structural analysis of Resvera-A according to pH.

5 is an enlarged view of LC MS / MS results for structural analysis of Resvera-A according to pH.

FIG. 6 shows the mechanism of Resvera-A structural change. FIG.

Claims (12)

An external preparation composition for skin containing a benzamide compound as an active ingredient, wherein the pH range of the composition is pH 5 or less. The external preparation composition for skin according to claim 1, wherein the benzamide compound is present in the composition in a state in which the substituent is not decomposed. According to claim 1, wherein the benzamide (benzamide) compound is Resvera-A (3,5-Dihydroxy-N- (4-hydroxyphenyl) benzamide), N-Phenylbenzamide (T-butylbenz) T-butylbenzamido hydroxybenzamide, 2-hydroxy-N-phenylbenzamide and t-butylbenzamido methylhydroxybenzamide The external preparation composition for skin, characterized in that it is selected from the group consisting of. The external preparation composition for skin according to claim 1, wherein the pH range is pH 3-5. 5. The composition for external application for skin according to claim 4, wherein the pH range is controlled by lactic acid, salicylic acid, glycolic acid or phosphate buffer solution of pH 5. The composition for applying the external of the skin according to claim 1, wherein the composition is for improving wrinkles. The composition for applying the external of the skin according to claim 1, wherein the composition is a cosmetic composition. 8. The composition for external application for skin according to claim 7, wherein the composition has a formulation of softening lotion, nourishing lotion, essence, lotion, emulsion or cream. A method for stabilizing a benzamide compound in an external composition for skin containing a benzamide compound as an active ingredient, A method for stabilizing a benzamide compound in an external composition for skin, characterized in that the pH range of the composition is adjusted to 5 or less by adding a pH adjusting agent to the composition. The method of claim 9, wherein the benzamide compound is Resvera-A (3,5-Dihydroxy-N- (4-hydroxyphenyl) benzamide), N-Phenylbenzamide, t-butylbenzamido hydride Consisting of t-butylbenzamido hydroxybenzamide, 2-hydroxy-N-phenylbenzamide and t-butylbenzamido methylhydroxybenzamide A method for stabilizing a benzamide compound in a topical skin composition, which is selected from the group. 10. The method of claim 9, wherein the pH adjusting agent is a lactic acid, salicylic acid, glycolic acid, or a phosphate buffer solution having a pH of 5. 10. The method of claim 9, wherein the pH range is pH 3-5.

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