KR100509717B1 - Anti-wrinkle cosmetic compositions - Google Patents

Abstract

The present invention relates to a method for preparing particles incorporating an anti-wrinkle active ingredient into a sericin-PEG conjugate represented by the following formula: 2- (O-methoxypolyethylene glycol) -4,6-dichloro-triazine (actPEG ₁ ) or 2,4-bis (O-methoxypolyethyleneglycol) -6-chloro-triazine (act PEG ₂ ) was reacted with sericin in a basic buffered aqueous solution to prepare PEG-sericin conjugates and then corrugated by dialysis in an organic solvent. It is characterized by producing a particle incorporating an improved active ingredient.

In the above formula, the molecular weight of actPEGn is 1,000-40,000.

Description

Anti-wrinkle cosmetic compositions

The present invention relates to a cosmetic composition for wrinkle improvement, to produce particles obtained by chemically bonding polyethylene glycol (PEG), a water-soluble polymer, to sericin, a natural protein obtained from silkworm cocoon, and incorporating a wrinkle enhancer into a conjugate obtained by a dialysis method. And it relates to a cosmetic composition for improving the wrinkles of the skin added to the cosmetic.

Cosmetic compositions containing nanoparticles have long-lasting anti-wrinkle or anti-oxidant titer compared to cosmetic products obtained by emulsion preparations having a particle size of micro-units. Excellent function to improve skin condition. Nanoparticles impregnated with anti-wrinkle agents are easily and high yielded by using a diafiltration method and have a size and spherical shape of less than 1 mm without association. In addition, nanoparticles with a size of less than 1 mm can be actively applied to various fields of life sciences such as separation technology, histological studies, clinical diagnostic methods, drug delivery, and functional cosmetics. It is because of its advantages in applications such as effective action and continuous drug release behavior (C. Cho et.al, Macromolecularie Chemie, Rapid Communication, 18 361-369 (1997)).

On the other hand, silk sericin, which is a natural polymer used in the present invention, has many hydroxyl groups, but has a property of being poorly soluble in a solvent due to physical properties of sericin itself. Therefore, chemically bonding polyethylene glycol (PEG) with excellent amphipathic properties makes it well soluble in organic solvents. Therefore, sericin-PEG conjugates can be dissolved in organic solvents to form nanoparticles. Therefore, they are suitable for functional cosmetics and pharmaceutical delivery by dialysis. It is possible to manufacture new self-assembled nanoparticles as possible (Korean Patent Application 2001-32990).

In addition, sericin is not at all toxic as the native protein components obtained from a cocoon is biodegradable and excellent polyethylene glycol (PEG) is a synthetic polymer, but it is known to compound non-toxic and is not an immune response harmful at all human body material (Poly ( ethylene glycol) Chemistry , JM Harris Eds., Plenum Press, 1992)

Retinol and retinol derivatives, tocopherol and tocopherol derivatives, 7-dehydroxycholesterol, ursolic acid, 2-deoxyadenosine, and the like are widely used as the anti-wrinkle agent, and retinol and retinol derivatives are the most widely used. However, the drawbacks of the anti-wrinkle agent is that it is easily oxidized by external environmental factors such as air or oxygen in the water or ultraviolet rays and its potency is lost when used in a general emulsion. Cosmetic scientists have made a lot of efforts to make up for these shortcomings and to develop formulations that have good anti-wrinkle effect while preserving the potency of the active substance for a long time, but have not yet obtained satisfactory results.

It is an object of the present invention to provide a method for preparing particles incorporating an active ingredient for wrinkle improvement.

Another object of the present invention is to prepare a wrinkle improvement cosmetic composition excellent in the wrinkle improvement effect while the titer of the wrinkle improvement agent is preserved for a long time.

The object of the present invention is to add a certain amount of activated polyethylene glycol ( actPEGn) to the aqueous solution of sericin having a controlled molecular weight and then react to remove the unreacted material using a dialysis membrane to prepare a sericin-PEG conjugate through lyophilization And it is dissolved by ethanol again with the active ingredient to proceed the dialysis and then lyophilized by the production method characterized in that to produce a particle containing a certain amount of the active ingredient.

Retinol, retinol palmitate, retinol acetate, retinoic acid, retinal, vitamin D1, vitamin D2, vitamin D3, vitamin D4, tocopherol, tocopherol acetate, 7-dehydroxycholesterol, ursolic acid, etc. may be used here. have.

actPEGn is one general formula

Wherein R ₁ and R ₂ are each CH ₃ O (CH ₂ -CH ₂ -O) n- and CH ₃ O (CH ₂ -CH ₂ -O) n- ( actPEG1 ) or CH ₃ O (CH ₂ -CH ₂ -O) n- and Cl ( actPEG2 ) and molecular weight range of 1,000-40,000 can be used.

As another actPEGn , activated PEG having the general formula

Where R ₁ is MeO-PEG-OCH ₂ CH _2- ( actPEG3 ), MeO-PEG-OCH ₂ CH ₂ CH _2- ( actPEG4 ), MeO-PEG-O ₂ CNH (CH ₂ ) 5- ( actPEG5 ), MeO -PEG-S-CH ₂ CH _2- ( actPEG6 ), MeO-PEG-NHCOCH ₂ CH _2- ( actPEG7 ), MeO-O ₂ (CH ₂ ) 3- ( actPEG8 ), MeO-PEG-O ₂ CCH ₂ CH _2- ( actPEG9 ), MeO-PEG-O- ( actPEG10 ), MeO-PEG-OCH _2- ( actPEG11 ) and the molecular weight range of 1,000-40,000 can be used and R ₂ , R ₃ , R ₄ is MeO-PEG- ( ActPEG12, actPEG13, actPEG14, respectively ) and the molecular weight range of 1,000-40,000 can be used and the amount can be used 10-20 times as weight percentage relative to the amount of sericin.

The sericin used may be hydrothermally extracted sericin or enzyme-treated sericin (molecular weight range 1,000-20,000). As the aqueous solution, a buffered aqueous solution of pH 8-10 may be used, and borate buffer, Tris buffer, AMPSO buffer, CHES buffer, CAPSO buffer, AMP buffer, and CAPS buffer may be used as the buffered aqueous solution. The reaction temperature of sericin and activated PEG is preferably 4-40C, and the reaction time is 3-36 hours. In order to incorporate the active ingredient into the sericin-PEG particles prepared by the above method, the sericin-PEG particles were ethanol, methanol, dimethylformamide, dimethyl sulfoxide, 1,3-butylene glycol, 1,2-propylene glycol, After dissolving in organic solvents such as glycerin, tetrahydrofuran, acetone, etc., add about 1/10 -10 times the active ingredient by weight. The mixed solution was put in a dialysis membrane (molecular weight cut-off 12,000), and dialyzed in distilled water for 24 hours, and then freeze-dried to prepare particles containing sericin-PEG particles containing the active ingredient.

The invention is illustrated in detail by the following examples. The following examples are merely to illustrate the present invention and the contents of the patent are not limited to the examples.

Preparation Example 1

12 mg of sericin (molecular weight 7,000) was dissolved in 12 ml of borate buffer at pH 9.4, and 27 mg of actPEG ₁ (MW 1,000) was added. After reacting at 4 ° C. for 24 hours, it was dissolved in ethanol and dialyzed for 24 hours using a dialysis membrane in distilled water. The dialysate was lyophilized to obtain 25 mg of sericin-PEG conjugate (Sericin-PEG1). (Yield 64%). 25 mg of the obtained sericin-PEG conjugate was dissolved in 5 ml of ethanol, and 2.5 mg of retinol was added thereto, followed by stirring in a shielded container for 30 minutes at room temperature. The mixed solution was placed in a dialysis membrane (molecular weight cut-off 12,000), dialyzed in distilled water for 24 hours, and freeze-dried to prepare particles containing retinol in sericin-PEG particles (yield 62%) by visible-ultraviolet spectroscopy. The amount of incorporated retinol analyzed was 4.20% by weight.

Preparation Example 2-13

Using the sericin-PEG particles prepared in Preparation Example 1 was tested by changing the active ingredients in the same manner as in Preparation Example 1 and the results are shown in Table 1.

Table 1.

  Preparation Example Active Ingredient Yield (%) Active Ingredient Content (w / w%)

2 Retinol Palmitate 50 17.5

3 Retinol Acetate 64 11.3

4 Retinoic acid 60 4.0

5 Retinal 68 4.8

6 Vitamin D1 52 3.6

7 Vitamin D2 50 2.8

8 Vitamin D3 53 3.2

9 Vitamin D4 55 3.8

10 Tocopherol 60 11.2

11 Tocopherol Acetate 62 9.9

12 7-dehydroxycholesterol 58 5.6

13 Ursolic Acid 56 1.2

Preparation Example 14

was dissolved 24mg of sericin in 12ml borate buffer of pH 9.4 was added to _{actPEG 12, (MW 2,000) 54mg} . After reacting at 4 ° C. for 24 hours, it was dissolved in ethanol and dialyzed for 24 hours using a dialysis membrane in distilled water. The dialysate was lyophilized to obtain 51 mg of sericin-PEG conjugate. Yield 65%.

51 mg of the obtained sericin-PEG conjugate was dissolved in 5 ml of ethanol, and then 5.1 mg of retinol was added and stirred in a light-shielded container at room temperature for 30 minutes. The mixed solution was put in a dialysis membrane (molecular weight cut-off 12,000), and dialyzed in distilled water for 24 hours, and then freeze-dried to prepare particles containing retinol in sericin-PEG particles. (Yield 64%) The amount of incorporated retinol analyzed by visible-UV spectroscopy was 4.6% by weight.

Preparation Example 15-26

Experiments were performed using the sericin-PEG particles prepared in Preparation Example 14 by changing the active ingredients in the same manner as in Preparation Example 14 and the results are shown in Table 2.

Table 2.

   Preparation Example Active Ingredient Yield (%) Active Ingredient Content (w / w%)

15 Retinol Palmitate 55 15.0

16 Retinol Acetate 66 10.1

17 Retinoic Acid 65 3.8

18 Retinal 72 4.0

19 Vitamin D1 48 3.2

20 Vitamin D2 53 3.9

21 Vitamin D3 60 4.0

22 Vitamin D4 60 3.2

23 Tocopherol 65 12.3

24 Tocopherol Acetate 60 11.0

25 7-dehydroxycholesterol 62 4.4

26 Ursolic Acid 55 1.1

Prescription Example 1.

A prescription example of a skin lotion (skin lotion) in cosmetics containing particles containing retinol in sericin-PEG is as follows. Retinol-embedded particles in sericin-PEG herein refer to those of Production Example 1.

number Raw material Formulation Example 1 Comparative Formulation Example 1 One Resin-incorporated particles in sericin-PEG 2.5 - 2 glycerin 3.0 3.0 3 Butylene Glycol 2.0 2.0 4 Propylene glycol 2.0 2.0 5 Polyoxyethylene (60) Cured Castor Oil 1.00 1.0 6 ethanol 10.0 10.0 7 Triethanolamine 0.1 0.1 8 antiseptic a very small amount a very small amount 9 Pigment a very small amount a very small amount 10 Spices a very small amount a very small amount 11 Purified water Remaining amount Remaining amount

<Manufacturing method>

Formulation Example 1 2, 3, 4, 8 No. 11 was added sequentially and stirred to dissolve 5 times

           After dissolving by heating at 60 ℃, add 10 times and stir to 11 times.

           Finally, 1, 6, 7, and 9 are added and sufficiently stirred before aging.

Comparative Formulation Example 1 No. 2, 3, 4, and 8 were added sequentially to No. 11, followed by stirring for dissolution.

           After dissolving by heating at 60 ℃, add 10 times and stir to 11 times.

Finally, add 6, 7, 9, and stir well before ripening .

Prescription Example 2.

A prescription example of nutrient lotion in cosmetics containing particles containing retinol in sericin-PEG is as follows. Retinol-embedded particles in sericin-PEG herein refer to those of Production Example 1.

number Raw material Formulation Example 2 Comparative Formulation Example 2 One Retinol-impregnated particles in sericin-PEG 2.5 - 2 Beeswax 1.00 1.0 3 Polysorbate 60 1.5 1.5 4 Sorbitan sesquioleate 0.5 0.5 5 Liquid paraffin 5.0 5.0 6 Squalane 5.0 5.0 7 Sorbitan stearate 1.00 1.00 8 Glyceryl Stearate / Pig-400 Stearate 1.00 1.00 9 Lipophilic monostearic acid glycerin 0.50 0.50 10 Stearic acid 1.50 1.50 11 Butylene glycol 5.00 5.00 12 Propylene glycol 5.00 5.00 13 Carboxy Vinyl Polymer 0.1 0.1 14 Triethanolamine 0.2 0.2 15 antiseptic a very small amount a very small amount 16 Pigment a very small amount a very small amount 17 Spices a very small amount a very small amount 18 Purified water Remaining amount Remaining amount

<Manufacturing method>

Formulation Example 2: 11, 12, 13, 15, 18 while stirring and mixing to 80 ~ 85 ℃ to the manufacturing part

          Actuate the emulsifier, and put 2,3,4,5,6,7,8,9,10,14 between 80 ~ 85 ℃

          Heat it, add it and emulsify it. After emulsification, use a stirrer to stir

          After cooling to 50 ℃, add 17 times and cool to 45 ℃.

          Input 16 times, add 1 time at 35 ℃, cool to 25 ℃ and mature.

          Let's do it.

Comparative Formulation Example 2 Preparation of 11, 12, 13, 15, 18 by Mixing and Stirring at 80 to 85 ° C

          After adding to the unit, the emulsifier is activated and 2,3,4,5,6,7,8,9,10,14 is used at 80 to 85 ° C.

          Heated through, emulsified. After emulsification, use a stirrer

          After cooling to 50 ℃ with stirring, add # 17 and cool to 45 ℃.

          Add 16 times, cool to 25 ℃, and age.

Prescription Example 3

A prescription example of a nourishing cream in cosmetics containing particles containing retinol in sericin-PEG is as follows. Retinol-embedded particles in sericin-PEG herein refer to those of Production Example 1.

number Raw material Formulation Example 3 Comparative Formulation Example 3 One Retinol-impregnated particles in sericin-PEG 2.5 - 2 Beeswax 5.00 5.00 3 Polysorbate 60 1.5 1.5 4 Sorbitan sesquioleate 0.5 0.5 5 Liquid paraffin 10.0 10.0 6 Squalane 10.0 5.0 7 Sorbitan stearate 1.00 5.0 8 Glyceryl Stearate / Pig-400 Stearate 1.00 5.0 9 Lipophilic monostearic acid glycerin 0.50 0.50 10 Stearic acid 1.50 1.50 11 Butylene glycol 5.00 3.00 12 Propylene glycol 5.00 3.00 13 Triethanolamine 0.2 0.2 14 antiseptic a very small amount a very small amount 15 Pigment a very small amount a very small amount 16 Spices a very small amount a very small amount 17 Purified water Remaining amount Remaining amount

<Manufacturing method>

Formulation Example 3: 11,12,14,17 while stirring to mix and heat to 80 ~ 85 ℃

          After the operation, operate the emulsifier and make 2,3,4,5,6,7,8,9,10,13 at 80 ~ 85 ℃.

          Heated through, emulsified. After emulsification, use a stirrer

          After cooling to 50 ℃ with stirring, add No. 16 and cool to 45 ℃.

          Add 15 times and add 1 when it cools down to 35 ℃. Cool down to 25 ℃

          After aging.

Comparative Formulation Example 3 : Manufacturing part by heating to 80-85 ° C while mixing and stirring 11, 12, 14, 17

          After the addition, the emulsifier is activated and 2,3,4,5, 6,7,8,9,10,13 is used at 80 to 85 ° C.

          Heated through, emulsified. After emulsification, use a stirrer

          After cooling to 50 ℃ with stirring, add No. 16 and cool to 45 ℃.

          15 times, cooled to 25 ℃ and aged.

Prescription Example 4.

A prescription example of a massage cream in cosmetics containing particles containing retinol in sericin-PEG is as follows. Retinol-embedded particles in sericin-PEG herein refer to those of Production Example 1.

number Raw material Formulation Example 4 Comparative Formulation Example 4 One Retinol-impregnated particles in sericin-PEG 2.5 - 2 Beeswax 10.0 10.0 3 Polysorbate 60 1.5 1.5 4 Sorbitan sesquioleate 0.8 0.8 5 Liquid paraffin 40.0 40.0 6 Squalane 5.0 5.0 7 Caprylic / Capric Triglycerides 4.0 4.0 8 Carboxy Vinyl Polymer 0.2 0.2 9 glycerin 5.0 5.0 10 Butylene glycol 3.0 3.0 11 Propylene glycol 3.0 3.0 12 Triethanolamine 0.2 0.2 13 antiseptic a very small amount a very small amount 14 Pigment a very small amount a very small amount 15 Spices a very small amount a very small amount 16 Purified water Remaining amount Remaining amount

<Manufacturing method>

Formulation Example 4 Prepared by heating to 80-85 ° C. while mixing and stirring 8,9,10,11,12,13,16

          After it is put into the unit, it operates the emulsifier and moves 2,3,4,5,6,7 to between 80 ~ 85 ℃.

          Heat it, add it and emulsify it. After emulsification, use a stirrer to stir

          After cooling to 50 ℃, add 15 times and cool to 45 ℃.

          Add 14 and add 1 when it cools to 35 ℃. Cool down to 25 ℃

          After aging.

Comparative Formulation Example 4 The mixture was stirred at 80 to 85 ° C. while mixing and stirring 8, 9, 10, 11, 12, 13, and 16

         After it is put into the manufacturing part, it operates the emulsifier and moves 2,3,4,5,6,7 to between 80 ~ 85 ℃.

         Heat it, add it and emulsify it. After emulsification, use a stirrer to stir

         After cooling to 50 ℃, add 15 times and cool to 45 ℃.

          14 times is added, cooled to 25 ℃ and aged.

Prescription Example 5.

A prescription example of a nutritional essence in cosmetics containing particles containing retinol in sericin-PEG is as follows. The particle | grains retinol impregnated here with sericin-PEG refer to the thing of Example 1.

number Raw material Formulation Example 5 Comparative Formulation Example 5 One Retinol-impregnated particles in sericin-PEG 2.5 - 2 Cytostolol 1.70 1.70 3 Polyglyceryl 2-oleate 1.50 1.50 4 Ceramide 0.7 0.7 5 Ceteares-4 1.2 1.2 6 cholesterol 1.5 1.5 7 Dicetylphosphate 0.4 0.4 8 Concentrated glycerin 5.0 5.0 9 Sunflower oil 15.0 15.0 10 Carboxy Vinyl Polymer 0.2 0.2 11 Xanthan Gum 0.2 0.2 12 antiseptic a very small amount a very small amount 13 Spices a very small amount a very small amount 14 Purified water Remaining amount Remaining amount

<Manufacturing method>

Formulation Example 5: Nonionic Parent by Homogenizing Raw Materials 2,3,4,5 and 6 at Constant Temperature

          Called tomic lipids. The nonionic amphiphilic lipids and raw materials 1,7,8

          And 14 and homogenized at constant temperature to obtain a microfluidizer.

          After passing through, the raw material 9 is gradually added and homogenized at a constant temperature.

          After passing through the microfluidizer again. And 10,11,12,13

          It is added, dispersed, stabilized and aged.

Comparative Formulation 5: Nonionicity by Homogenizing Raw Materials 2,3,4,5 and 6 at Constant Temperature

          Amphiphilic lipids. The nonionic amphiphilic lipid and raw material

          Microfluidizer by mixing 7, 8 and 14 and homogenizing at constant temperature

          And then slowly add raw material 9 at a constant temperature

          After homogenization, pass it again through the microfluidizer.

          10, 11, 12, 13 is added to disperse to stabilize and mature.

Prescription Example 6

Prescription examples of emulsified foundations in cosmetics containing particles containing retinol in sericin-PEG are as follows. Retinol-embedded particles in sericin-PEG herein refer to those of Production Example 1.

number Raw material Formulation Example 6 Comparative Formulation Example 6 One Retinol-impregnated particles in sericin-PEG 2.5 - 2 Beeswax 2.0 2.0 3 Pyromethicone 2.0 2.0 4 Liquid paraffin 5.0 5.0 5 Squalane 5.0 5.0 6 Stearic acid 2.0 2.0 7 Lipophilic monostearic acid glycerin 3.0 3.0 8 Caprylic / Capric Triglycerides 4.0 4.0 9 glycerin 4.0 4.0 10 Propylene glycol 3.0 3.0 11 Butylene glycol 3.0 3.0 12 Triethanolamine 1.0 1.0 13 Aluminum Magnesium Silicate 0.5 0.5 14 Pigment 12 12 15 antiseptic a very small amount a very small amount 16 Spices a very small amount a very small amount 17 Purified water Remaining amount Remaining amount

<Manufacturing method>

Formulation Example 6: The mixture is heated to 80 to 85 ° C while stirring and stirring 9,10,11,12,13,14,15,17

          After it is put into the manufacturing part, it operates the emulsifier and makes 2,3,4,5,6,7,8 at 80 ~ 85

          Heated through, emulsified. After emulsification, use a stirrer

          After cooling to 45 ℃ with stirring, add No. 16 and cool to 35 ℃

           Input 1 After cooling to 25 ° C, aging.

Comparative Formulation Example 6: Heating between 80 and 85 ° C. while stirring and mixing 9, 10, 11, 12, 13, 14, 15, and 17

         To the manufacturing unit, and then actuated an emulsifier.

         Heat it in between to emulsify. After emulsification, use a stirrer

         After cooling to 45 ℃ with stirring, add No. 16 and cool to 25 ℃

         Mature.

Test Example 1 Stability Test of Active Ingredients

In order to test the stability of the active ingredient in the particles added to the formulation, the safety test was performed by measuring the content of the active ingredient at room temperature for 6 months. Retinol, which was used in the formulation of Formulation Example 5, was added at 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks immediately after addition to the prescription. The amount of titer reduction was analyzed based on the content of. The analysis results are shown in FIG. 1.

Fast liquid chromatography was used and the analysis conditions were as follows.

column ; Stmmetry C ₁₈ 4.6 x 250 mm (Waters)

Mobile phase; THF / acetonitrile = 20/80

Flow rate; 1.0ml / min

Detector; UV 325 nm (photodiode detector; 996 Waters)

Injection volume; 20ul

As shown in FIG. 1, the content of retinol added after 24 weeks, starting from the initial 98% content, is maintained at 90% or more, indicating that the particles are very stable to the external environment.

Test Example 2-13

In place of the retinol-containing particles of Formulation Example 5, the stability was measured by the method similar to the above using Preparation Example 2 to Preparation Example 13, and the residual amount result after 24 weeks is shown in Table 3.

Table 3.

Test Example Production Example Remaining Active Ingredient Content (%) ¹⁾

2 2 95

3 3 94

4 4 97

5 5 92

6 6 91

7 7 95

8 8 90

9 9 91

10 10 93

11 11 96

12 12 96

13 13 99

¹⁾ Residual content relative to the amount of active ingredient initially incorporated

Test Example 14 Skin Elasticity Enhancement Effect of Formulation Containing Particles with Active Ingredients

Formulation Example 5 was applied twice a day to the edges of the left eye of 20 people to test the effect of increasing the elasticity of the skin when the nutritional essences of Formulation Example 5 and Comparative Formulation 5 were applied to the skin. Comparative Example 5 was applied to the right eye edge. After each treatment, the skin elasticity of the skin surface was measured by Cutometer SEM 474. Skin elasticity measurement by Cutometer SEM 474 is a method of measuring the extent of inhalation by inhaling the epidermis with negative pressure. The smaller the value, the better the elasticity. The elasticity value was shown as a percentage decrease compared to the control, and the average value of 20 subjects is shown in Table 4. The control is the measurement before processing the sample.

Table 4.

Sample skin elasticity effect (%)

30 days 45 days

Formulation Example 5 26.5 32.7

Comparative Formulation Example 5 9.7 13.6

Test Example 15. Wrinkle improvement effect through image analysis of formulation containing particles containing active ingredient

The subject was photographed with wrinkles around both eyes using Camscop, a high-resolution digital camera for wrinkling, and a photodamage score (0: none, 1: none / slightly, 2: slightly, 3: slightly / Normal, 4: Moderate, 5: Moderate / Severe, 6: Severe, 7: Very severe, see: Arch. Dermatol.vol . 137 (8): 1043-1051, 2001) Efficacy differences between Comparative Formula 5 were compared weekly.

    From the 4th week of the test, the test product showed statistically significant (2.4 ± 0.58 vs 2.52 ± 0.59, p = 0.04) wrinkle improvement compared to the control. This tendency becomes more pronounced with longer test periods, with statistically distinct differences between 8 weeks (1.92 ± 0.76 vs 2.28 ± 0.68, p = 0.002) and 12 weeks (1.36 ± 0.91 vs 2.24 ± 0.72, p = 0.000004). Seemed. Table 5 divides the improvement effect observed in the photodamage score of the image analysis by four stages of scale (no change, mild, good, remarkable), and shows the number of subjects as a percentage.

     The rate of wrinkle improvement at the site of use of the test product was higher than that of the control product over the entire test period. At the end of the 12-week trial, the test product showed better than good results in 56% of subjects, while only 8% of the control products showed good improvement.

Table 5.

Formulation 5 Comparative Formulation 5

4 weeks 8 weeks 12 weeks 4 weeks 8 weeks 12 weeks

No change 18 (72%) 9 (36%) 4 (16%) 21 (84%) 15 (60%) 15 (60%)

Minor 7 (28%) 10 (40%) 7 (28%) 4 (16%) 9 (36%) 8 (32%)

Good 5 (20%) 7 (28%) 1 (4%) 2 (8%)

Mark 1 (4%) 7 (28%)

Total 25 (100%) 25 (100%) 25 (100%) 25 (100%) 25 (100%) 25 (100%)

The particles produced by the present invention improve the stability of the wrinkle improvement ingredients such as retinol, and when added to cosmetics is excellent effect to improve skin elasticity and wrinkles.

1 is a graph showing the results of experiments on the stability of the active ingredient in the particles prepared by the present invention.

Claims (10)

Sericin 2- (O-methoxyethyleneglycol) -4,6-dichloro-triazine ( actPEG ₁ ) or 2,4-bis (O-methoxyethyleneglycol) -6-chloro-triazine ( actPEG ₂ ) Reacting in a basic buffered aqueous solution to prepare a sericin-PEG conjugate and dissolving it in an organic solvent and incorporating the anti-wrinkle active ingredient therein to prepare particles having the anti-wrinkle active ingredient in the sericin-PEG conjugate. The active ingredient according to claim 1, wherein the anti-wrinkle active ingredient is retinol, retinol palmitate, retinol acetate, retinoic acid, retinal, vitamin D1, vitamin D2, vitamin D3, vitamin D4, tocopherol, tocopherol acetate, 7-dehydroxycholesterol And at least one component selected from the group consisting of ursolic acid. The organic solvent according to claim 1 or 2, wherein the organic solvent used is water, methanol, ethanol, dimethylformamide, dimethyl sulfoxide, 1,3-butylene glycol, 1,2-propylene glycol, glycerin, acetone, and tetra At least one organic solvent selected from the group consisting of hydrofuran. Activated PEG of the following general formula to sericin in a basic buffered aqueous solution to prepare a sericin-PEG conjugate, dissolved in an organic solvent, and incorporated therein into the anti-wrinkle active ingredient, the anti-wrinkle active ingredient is incorporated into the sericin-PEG conjugate. To prepare the particles: Where R ₁ is MeO-PEG-OCH ₂ CH _2- ( actPEG3 ), MeO-PEG-OCH ₂ CH ₂ CH _2- ( actPEG4 ), MeO-PEG-O ₂ CNH (CH ₂ ) 5- ( actPEG5 ), MeO -PEG-S-CH ₂ CH _2- ( actPEG6 ), MeO-PEG-NHCOCH ₂ CH _2- ( actPEG7 ), MeO-O ₂ (CH ₂ ) 3- ( actPEG8 ), MeO-PEG-O ₂ CCH ₂ CH _2- ( actPEG9 ), MeO-PEG-O- ( actPEG10 ), MeO-PEG-OCH _2- ( actPEG11 ) and R ₂ , R ₃ , R ₄ are MeO-PEG- ( actPEG12, actPEG13, actPEG14, respectively ). The anti-wrinkle active ingredient according to claim 4, wherein the anti-wrinkle active ingredient is retinol, retinol palmitate, retinol acetate, retinoic acid, retinal, vitamin D1, vitamin D2, vitamin D3, vitamin D4, tocopherol, tocopherol acetate, 7-dehydroxycholesterol And at least one component selected from the group consisting of ursolic acid. The organic solvent according to claim 4 or 5, wherein the organic solvent used is water, methanol, ethanol, dimethylformamide, dimethyl sulfoxide, 1,3-butylene glycol, 1,2-propylene glycol, glycerin, acetone, and tetra At least one organic solvent selected from the group consisting of hydrofuran. Cosmetic composition containing particles prepared by the method of claim 1. The cosmetic composition according to claim 7, wherein the cosmetic composition has a formulation of a lotion (skin lotion), nutrition lotion, nutrition cream, massage cream, or nutrition essence. Cosmetic composition containing particles prepared by the method of claim 4. The cosmetic composition according to claim 9, wherein the cosmetic composition has a formulation of a lotion (skin lotion), a nutrition lotion, a nutrition cream, a massage cream, or a nutritional essence.