High-stability resorcinol anhydrous self-assembly composition as well as preparation method and application thereof

Abstract

The invention discloses a high-stability resorcinol anhydrous self-assembly composition as well as a preparation method and an application thereof. The composition comprises 20-45% of an emulsifier; 10%-20% of a resorcinol derivative; 30%-60% of a polyol; 0.01%-0.1% of a pH regulator; 0.01%-0.1% of a chelating agent; 0.01%-0.1% of an antioxidant; the mass ratio of the emulsifier to the resorcinol derivative is (2-3): 1; the emulsifying agent is prepared from PPG-6-decyl tetradecyl alcohol polyether-30 and PPG-4-cetyl alcohol polyether-20, and the mass percent of the PPG-6-decyl tetradecyl alcohol polyether-30 in the emulsifying agent is greater than 50%. An O / P vesicle structure is formed, and the stability, the transdermal effect and the bioavailability of the active matter are effectively improved.

Description

Technical Field

[0001] The present invention belongs to the fields of colloid chemistry and surface chemistry, and particularly relates to a highly stable resorcinol anhydrous self-assembled composition, a preparation method thereof, and an application thereof. Background Art

[0002] Resorcinol derivatives have been found to have extremely strong potential whitening effects: in vitro experiments have also proven that they are dozens or even hundreds of times stronger than VC, and their whitening ability has been clinically confirmed. The most crucial thing is that they have a fast whitening speed and are gradually used in cosmetics.

[0003] However, at present, hydroquinone derivatives have the following disadvantages: resorcinol derivatives are extremely unstable in the formulation of cosmetics. The common color change in creams is from milky white to pink, or even dark brown, and this change occurs within a very short time, which makes the product lose its sensory pleasure in appearance use. Moreover, the varying degrees of unstable appearance caused by color change are difficult to standardize in production. The reasons for the color change of resorcinol are as follows: 1) Oxidation: Resorcinol is easily oxidized by oxygen, especially when in contact with air or exposed to light for a long time. This will cause it to gradually turn brown or black. 2) Photosensitivity: Resorcinol is sensitive to ultraviolet and visible light, which also causes its color change. When resorcinol is exposed to sunlight or strong light, its molecular structure changes, resulting in color change. 3) Impurities or reaction products: Resorcinol changes color due to chemical reactions with other substances or the presence of impurities. Interaction with metal ions, certain organic compounds or other chemical substances leads to the formation of pigments or color change. How to effectively isolate active oxygen, reduce the catalytic effect of trace metal ions in the system on the oxidation reaction, provide a certain electron donor ability, competitively combine with free radicals, make the free radicals relatively stable, thereby interrupting the attack of free radicals on phenolic hydroxyl groups, inhibiting the progress of the oxidation reaction, and thus greatly improving the stability of phenolic hydroxyl compounds and delaying the color change reaction.

[0004] In addition, resorcinol derivatives are poorly soluble in water and are irritating to the skin. These factors greatly reduce their biological activity in cosmetic applications, resulting in their efficacy not being maximally exerted.

[0005] Therefore, how to improve the stability, water solubility, biocompatibility, and transdermal absorption of resorcinol derivatives, so that they have a wider application range in the cosmetic field and exert their whitening, freckle-removing, and antioxidant effects, is a technical problem worthy of research. Summary of the Invention

[0006] The purpose of this section is to outline some aspects of the embodiments of the present invention and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section, as well as in the abstract and title of the present application, to avoid obscuring the purpose of this section, the abstract, and the title. However, such simplifications or omissions shall not be used to limit the scope of the present invention.

[0007] In view of the above problems and / or problems existing in the prior art, the present invention is proposed.

[0008] Therefore, an object of the present invention is to overcome the deficiencies in the prior art and provide a method for preparing a highly stable resorcinol anhydrous self-assembled composition, which, by mass percentage, includes

[0009]

[0010] The mass ratio of the emulsifier to the resorcinol derivative is 2-3:1; the emulsifier is composed of PPG-6-decyltetradeceth-30 and PPG-4-ceteth-20, and the mass percentage of PPG-6-decyltetradeceth-30 in the emulsifier is greater than 50%;

[0011] The pH regulator, chelating agent, antioxidant, and polyol are stirred evenly at 40-60°C, the emulsifier is added, and stirring is continued until transparent. After cooling to room temperature, the resorcinol derivative is added and stirred evenly until transparent.

[0012] As a preferred embodiment of the method for preparing a highly stable resorcinol anhydrous self-assembled composition according to the present invention: the resorcinol derivative is one or more of 4-butylresorcinol, phenethylresorcinol, hexylresorcinol, dimethoxytolyl-4-propylresorcinol, isobutyrylaminothiazolylresorcinol, and glabridin.

[0013] As a preferred embodiment of the method for preparing a highly stable resorcinol anhydrous self-assembled composition according to the present invention: the polyol is composed of one or more of propylene glycol, butylene glycol, and pentylene glycol.

[0014] As a preferred embodiment of the method for preparing a highly stable resorcinol anhydrous self-assembled composition according to the present invention: the polyol is composed of propylene glycol, butylene glycol, and pentylene glycol; wherein, by mass ratio, the mass ratio of propylene glycol, butylene glycol, and pentylene glycol is (2-4):(0.5-1):(0.5-1).

[0015] As a preferred embodiment of the method for preparing a highly stable resorcinol anhydrous self-assembled composition according to the present invention: the pH regulator includes citric acid or succinic acid.

[0016] As a preferred embodiment of the preparation method of the highly stable resorcinol anhydrous self-assembled composition of the present invention: The antioxidant is one or more of sodium metabisulfite, sodium bisulfite, and sodium phytate.

[0017] As a preferred embodiment of the preparation method of the highly stable resorcinol anhydrous self-assembled composition of the present invention: The chelating agent is one or more of EDTA-2Na, EDTA-3Na, EDTA-4Na, ethylenediaminetetraacetic acid, and trisodium ethylenediaminedisuccinate.

[0018] Another object of the present invention is to overcome the deficiencies in the prior art and provide an application of a highly stable resorcinol anhydrous self-assembled composition in cosmetics, where the cosmetics are selected from one or more of facial cleansers, facial masks, lotions, creams, and essences.

[0019] Advantages of the present invention:

[0020] (1) The present invention uses a special combination of emulsifiers and polyols to form a self-assembled O / P vesicle system with resorcinol derivatives. This system can effectively protect resorcinol derivatives, isolate them from reactive oxygen species, and delay the oxidation of phenolic hydroxyl compounds. The stability of the active substance at high temperature (50°C) for one month can reach more than 90%.

[0021] (2) For the highly stable resorcinol anhydrous self-assembled composition prepared by the present invention, the mass ratio of the emulsifier to resorcinol is 2:1 to 3:1, and PPG-4-ceteth-20 and PPG-6-decyltetradeceth-30 are used in combination. By combining low-carbon-chain polyols with suitable PPG-based polyether emulsifiers, the hydroxyl groups of the polyols can form hydrogen bonds with the emulsifiers, enhancing the strength and compactness of the interfacial film, forming a stable equilibrium system, effectively isolating the active substance from the outside, thereby improving the stability of the active substance and reducing skin irritation.

[0022] (3) The present invention can achieve the dissolution and stability of the active substance with a lower proportion of emulsifiers, which is a significant difference from conventional solubilization systems. With a low content of emulsifiers, the content of emulsifiers introduced during the later formulation can be significantly reduced, effectively reducing the irritation and poor skin feel caused by emulsifiers in the formulation.

[0023] (4) The highly stable resorcinol anhydrous self-assembled composition prepared by the present invention improves the stability and transdermal absorption rate of the active ingredient, significantly reduces its irritation, and enhances its whitening effect. Description of the Drawings

[0024] To more clearly illustrate the technical solutions of the embodiments of the present invention, the following will briefly introduce the accompanying drawings required for the description of the embodiments. Obviously, the accompanying drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other accompanying drawings can be obtained based on these drawings. Among them:

[0025] Figure 1 It is the TEM photograph of the sample prepared in Example 1 of the present invention.

[0026] Figure 2 It is the test result of the stability experiment of the active substance content of the sample in Example 2 of the present invention.

[0027] Figure 3 It is the appearance comparison diagram of the sample in Example 3 of the present invention.

[0028] Figure 4 It is the transdermal experiment result of the sample in Example 5 of the present invention. Specific Embodiments

[0029] To make the above objects, features, and advantages of the present invention more obvious and understandable, the following will make a detailed description of the specific embodiments of the present invention in combination with the embodiments of the specification.

[0030] All raw materials in the present invention are ordinary commercially available products.

[0031] Example 1

[0032] Prepare an emulsion according to the raw material ratio in Table 1:

[0033] Emulsion preparation method: Weigh the pH regulator (citric acid), chelating agent (DTA-2Na), antioxidant (sodium bisulfite), and polyol into a beaker, dissolve and stir evenly at 50°C, then add the emulsifier, continue to stir until transparent, and after cooling to room temperature, add the resorcinol derivative in portions and stir until a transparent solution is obtained.

[0034] Table 1 Raw material ratio table (unit: wt%)

[0035]

[0036]

[0037] The results show that the compositions prepared from Samples 1, 2, 5, and 6 can form a transparent solution; it is difficult for other samples to form a transparent system, and active substances precipitate.

[0038] Use TEM to measure Sample 1, as shown in Figure 1 , and obvious vesicle structures can be observed.

[0039] Example 2

[0040] Table 2 Determination of the Stability of Active Substances

[0041]

[0042] Preparation of Sample 2: At 50 °C, mix 4-butylresorcinol with isononyl isononanoate in a ratio of 5:95 (mass ratio) and stir until a clear solution is obtained.

[0043] Experimental method:

[0044] Store the sample at 50 °C and regularly test the content of the active substance to investigate the stability of 4-butylresorcinol in the composition.

[0045] Determine the content of 4-butylresorcinol in the sample by high performance liquid chromatography.

[0046] The experimental results of the stability of the active substance content are as Figure 2 shown. It can be seen from the results that the stability of 4-butylresorcinol in the composition of the present invention is significantly improved compared with that of free 4-butylresorcinol, and the retention rate of the high-temperature active substance can reach 90% after one month.

[0047] Example 3

[0048] Table 3 Stability Determination

[0049] Sample 11 12 PPG-6-decyltetradeceth-30 0.2 0.2 PPG-4-ceteth-20 0.15 0.15 4-Butylresorcinol 0.15 0.15 Propylene Glycol 0.3 0.3 Butylene Glycol 0.1 0.1 Hexylene Glycol 0.0985 0.0985 Citric Acid 0.0005 0.0005 EDTA-2Na 0.0005 0.0005 Sodium Bisulfite 0.0005 0.0005 Water 99 99

[0050] Preparation of Sample 11: Weigh the pH regulator, chelating agent, antioxidant and polyol into a beaker, dissolve and stir evenly at 50 °C, then add the emulsifier and continue to stir until transparent. After cooling to room temperature, add 4-butylresorcinol in portions and stir until a clear solution is obtained. Dilute with water in proportion.

[0051] Preparation of Sample 12: Weigh the pH regulator, chelating agent, antioxidant and emulsifier and dissolve them in water. Weigh 4-butylresorcinol and dissolve it in polyol. Mix the two according to the proportion.

[0052] The experimental results of the stability are as Figure 3 shown. It can be seen from the results that the stability of 4-butylresorcinol in the water dilution of Sample 11 of the present invention is significantly better than that of 4-butylresorcinol in Comparative Sample 12, and obvious precipitation and turbidity of the active substance occur in Comparative Sample 12.

[0053] Example 4

[0054] Application example:

[0055] 1. Whitening Milk 1

[0056] Table 4

[0057]

[0058]

[0059] 2. Whitening Milk 2

[0060] Table 5

[0061]

[0062]

[0063] Whitening Milk 1 uses the highly stable composition prepared by the present invention (Sample 1 in Example 1), with an addition amount of 5%, corresponding to a 4-butylresorcinol content of 0.075%. Whitening Milk 2 uses 4-butylresorcinol powder, with an addition amount of 0.075%.

[0064] Example 5

[0065] Transdermal experiment:

[0066] 1 Whitening Milk 1 in Example 3 2 Whitening Milk 2 in Example 3

[0067] Experimental method:

[0068] Throughout the experiment, intact and undamaged pig skins with comparable thicknesses are selected for the transdermal experiment. After cutting the pig skins into pieces of about 2.5 cm × 2.5 cm, they are placed between the receiving chamber and the supply chamber of the Franz diffusion cell, with the stratum corneum side facing the supply chamber;

[0069] The receiving chamber contains PBS buffer solution (pH = 7.4) with 5% Tween 80;

[0070] Add 2 mL of the sample to the supply chamber;

[0071] Place the assembled Franz diffusion cell into the transdermal diffusion instrument, and set the experimental conditions as follows: temperature is 37°C, stirring speed is 400 rpm, and transdermal time is 12 h.

[0072] After the transdermal experiment is completed, take out the pig skin from the diffusion cell, wipe the remaining sample on the surface of the pig skin with absorbent cotton, and then use the tape stripping method to determine the content of polysaccharides in the stratum corneum. Stick 21 layers of skin on the surface of the pig skin with 3M tape, discard the first layer, place the remaining 20 layers in a 15 mL centrifuge tube, first add 2 mL of isopropanol to the tube, ultrasonicate for 30 min, centrifuge at 5000 rpm for 30 min, take the supernatant, filter it with a 0.22 μm organic filter membrane, and then determine the content of 4-butylresorcinol, which is the content of 4-butylresorcinol in the stratum corneum.

[0073] Heat the remaining skin surface at 60 °C for 15 s, carefully cut off the viable epidermis with a scalpel, cut it into pieces and place it in a 15 mL centrifuge tube. Add 2 mL of isopropanol, sonicate for 30 min, centrifuge at 5000 rpm for 30 min, take the supernatant, filter it through a 0.22 μm organic filter membrane, and then determine the content of 4-butylresorcinol, which is the content of 4-butylresorcinol in the viable epidermis.

[0074] Cut the last remaining skin into pieces and place it in a 15 mL centrifuge tube. Add 2 mL of isopropanol, sonicate for 30 min, then centrifuge at 5000 rpm for 30 min, take the supernatant, filter it through a 0.22 μm organic filter membrane, and then determine the content of 4-butylresorcinol, which is the content of 4-butylresorcinol in the dermis.

[0075] The content of 4-butylresorcinol was determined by high performance liquid chromatography.

[0076] The results of the transdermal experiment are as Figure 4 shown. It can be seen from the results that Whitening Milk 1 is significantly better than Whitening Milk 2 in both the viable epidermis and the dermis (p < 0.05), indicating that the transdermal effect of 4-butylresorcinol after self-assembly in the highly stable composition prepared by the present invention is significantly better than that of free 4-butylresorcinol. This self-assembly system effectively improves the transdermal absorption effect of the active ingredient 4-butylresorcinol and increases its bioavailability.

[0077] Example 6

[0078] Patch test

[0079]

[0080] Preparation of Sample 2: At 50 °C, mix phenethyl resorcinol with olive oil at a ratio of 0.5:99.5 (mass ratio) and stir until a clear solution is obtained.

[0081] Select 50 volunteers aged 18 - 35 years old, randomly divide them into 5 groups, with 10 people in each group. Refer to the relevant requirements of "Human Skin Patch Test" in "Hygiene Standard for Cosmetics" (2015 Edition) to conduct human skin adverse reaction tests.

[0082] Patch test method: The flexor side of the forearm is used as the test site, with an area of 3 × 3 cm 2 , and the test site should be kept dry. Apply 0.020 ml of the test substance evenly on the test site twice a day for 7 consecutive days. At the same time, observe the skin reaction and record the results according to the skin reaction grading standard (Table 6) in "Technical Specifications for Cosmetics Safety" (2015 Edition) (Table 7).

[0083] Table 6 Skin reaction grading standard for skin open patch test

[0084]

[0085] Table 7 Results of Human Patch Test of Whitening Lotion

[0086]

[0087]

[0088] It can be seen from Table 7 that the test results of applying Sample 1 are all negative, and no adverse skin reactions occurred. There was slight irritation in the test results of Sample 2. It is proved that the composition prepared by the present invention effectively reduces the irritation of the active substance.

[0089] Example 7

[0090] Table 8 Raw Material Ratio Table (unit: wt%)

[0091]

[0092]

[0093] The method for preparing the lotion is the same as that in Example 1.

[0094] The results show that: the composition prepared from Sample 17 can form a transparent solution; it is difficult for other samples to form a transparent system, and active substances precipitate. The present invention uses a combination of an emulsifier and a polyol to form a self-assembled O / P vesicle system with a resorcinol derivative. This system effectively protects the resorcinol derivative, isolates it from reactive oxygen species, and delays the oxidation of the resorcinol derivative. Among them, PPG-4-ceteth-20 needs to be used in combination with PPG-6-decyltetradeceth-30 to effectively form self-assembled vesicles.

[0095] It should be noted that the above examples are only used to illustrate the technical solutions of the present invention and are not intended to limit. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced without departing from the spirit and scope of the technical solutions of the present invention, and they should all be covered within the scope of the present invention.

Claims

1. A preparation method of a highly stable resorcinol anhydrous self-assembled composition, characterized in that: By mass percentage, it includes emulsifier 20% - 45%; resorcinol derivative 10% - 20%; polyol 30% - 60%; pH regulator 0.01% - 0.1%; chelating agent 0.01% - 0.1%; antioxidant 0.01% - 0.1%; The mass ratio of the emulsifier to the resorcinol derivative is 2 - 3:1; the emulsifier is composed of PPG - 6 - decyltetradeceth - 30 and PPG - 4 - ceteth - 20, and the mass percentage of PPG - 6 - decyltetradeceth - 30 in the emulsifier is greater than 50%; The pH regulator, chelating agent, antioxidant and polyol are stirred evenly at 40 - 60 °C, the emulsifier is added, and stirring continues until transparent. After cooling to room temperature, the resorcinol derivative is added and stirred evenly until transparent.

2. The preparation method of the highly stable resorcinol anhydrous self-assembled composition according to claim 1, wherein: The resorcinol derivative is one or more of 4 - butylresorcinol, phenethylresorcinol, hexylresorcinol, dimethoxytolyl - 4 - propylresorcinol, isobutyrylaminothiazolylresorcinol, glabridin.

3. The preparation method of the resorcinol anhydrous self-assembly composition with high stability according to claim 1 or 2, characterized in that: The polyol is composed of one or more of propylene glycol, butylene glycol and pentylene glycol.

4. The preparation method of the highly stable resorcinol anhydrous self-assembled composition according to claim 3, characterized in that: The polyol is composed of propylene glycol, butylene glycol and pentylene glycol; among them, by mass ratio, the mass ratio of propylene glycol, butylene glycol and pentylene glycol is (2 - 4):(0.5 - 1):(0.5 - 1).

5. The preparation method of the highly stable resorcinol anhydrous self-assembled composition according to claim 1 or 2, characterized in that: The pH regulator includes citric acid or succinic acid.

6. The preparation method of the highly stable resorcinol anhydrous self-assembled composition according to claim 1 or 2, characterized in that: The antioxidant is one or more of sodium metabisulfite, sodium bisulfite, sodium phytate.

7. The preparation method of the highly stable resorcinol anhydrous self-assembled composition according to claim 1 or 2, characterized in that: The chelating agent is one or more of EDTA - 2Na, EDTA - 3Na, EDTA - 4Na, ethylenediaminetetraacetic acid and trisodium ethylenediaminedisuccinate.

8. A resorcinol anhydrous self - assembling composition prepared by the preparation method of the highly stable resorcinol anhydrous self - assembling composition according to claim 1.

9. Use of a resorcinol anhydrous self - assembling composition prepared by the preparation method of the highly stable resorcinol anhydrous self - assembling composition according to claim 1 in the preparation of cosmetics with whitening efficacy.

10. The application according to claim 9, characterized in that: The cosmetics include one or more of facial cleanser, facial mask, lotion, emulsion, cream, essence.

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