CN115363973A - 4-butyl resorcinol co-delivery nano-carrier and preparation method and application thereof - Google Patents

Abstract

The invention relates to the technical field of IPC A61K, in particular to a 4-butyl resorcinol co-delivery nano-carrier and a preparation method and application thereof. The raw materials comprise the following components in percentage by weight: 5-12% of 4-butyl resorcinol, 5-15% of C2-C9 alcohol, 4-10% of polyglycerol fatty acid ester, 2-10% of vitamin derivative, 1-15% of emollient, 0.01-2% of anti-inflammatory agent and the balance of solvent. According to the application, active ingredients such as 4-butylresorcinol and the like are repeatedly encapsulated in the nanoemulsion with the particle size of 10-100nm through a nano-carrier targeted transmission technology, the obtained carrier enables whitening and skin-care ingredients to easily permeate into a skin dermis basal layer, and the effects of efficiently inhibiting melanin and brightening skin can be realized only by a very small amount of functional ingredients due to high targeting property and bioavailability.

Description

4-butyl resorcinol co-delivery nano-carrier and preparation method and application thereof

Technical Field

The invention relates to the technical field of IPC A61K, in particular to a 4-butyl resorcinol co-delivery nano-carrier and a preparation method and application thereof.

Background

With the increase of aesthetic consciousness and consumption level of consumers, whitening has become a mainstream cosmetic function which is popular in the market. The whitening effect of the cosmetics on skin mainly depends on functional components absorbed by the skin, the whitening components on the market are mainly concentrated in arbutin, vitamin C and derivatives, tranexamic acid and the like at present, and the whitening effect is achieved by inhibiting pigmentation in the skin. However, these cosmetics still have the following problems: (1) The product efficacy and the cost are difficult to balance, the active ingredient of the skin care product with low cost is single, and the synergistic effect of various functional ingredients is lacked; the skin care product added with various functional components is high in price and difficult to be accepted by market consumer groups; (2) The formula of the functional components has poor compatibility and environmental tolerance, is difficult to fully dissolve in a system, has high precipitation tendency and poor thermal stability, is easy to decompose and discolor under the illumination condition, and can not be stored for a long time; (3) The bioavailability of the functional components is low, the functional components are difficult to reach a target part through a deep skin structure, and the efficacy is difficult to fully exert; (4) The safety and the efficacy of the product are difficult to balance, and although some efficacy components have obvious skin care effect, the skin is stimulated, so that the problem of skin sensitivity is easily caused, and the safety and the comfort are difficult to take into account.

Chinese patent CN202110423017.8 discloses a transparent whitening essence containing 4-butyl resorcinol and a preparation method thereof, chinese patent CN202010656244.0 discloses a whitening and spot-lightening composition and an application thereof, and Chinese patent CN201910591678.4 discloses a skin-whitening cream, and the prior arts all add 4-butyl resorcinol into skin care products, but cannot solve the technical problems at the same time.

Disclosure of Invention

In order to solve the problems, the invention provides a 4-butyl resorcinol co-delivery nano-carrier which comprises the following raw materials in percentage by weight: 5-12% of 4-butyl resorcinol, 5-15% of C2-C9 alcohol, 4-10% of polyglycerol fatty acid ester, 2-10% of vitamin derivative, 1-15% of emollient, 0.01-2% of anti-inflammatory agent and the balance of solvent.

The nano carrier provided by the application is rich in various functional components, can load functional components with different action mechanisms in the same nano carrier at the same time, provides multi-level repair and protection for skin, and realizes multi-target point inhibition of polyphenol oxidase activity in vivo and inhibition of melanin formation and in vivo deposition; on one hand, the exfoliation of aged keratinocytes is limited, the damaged lipid barrier is repaired, and the skin resistance is improved; meanwhile, the skin care product can inhibit the generation of inflammatory cytokines and cell mediators, improve the skin tolerance, and adjust the skin immunity, anti-allergy and anti-oxidation capabilities; it also has effects in improving dullness and lackluster of skin, whitening skin, removing mottle, improving uneven skin color, and reducing skin pigmentation caused by ultraviolet irradiation.

In some preferred embodiments, the C2-C9 alcohol comprises a combination of one or more of hexylene glycol, pentylene glycol, diethylene glycol monoethyl ether, butylene glycol, glycerol, sorbitol.

In some preferred embodiments, the C2-C9 alcohol has a molecular weight of 85-142 and a flash point of 90-143 ℃ (open).

Further preferably, the C2-C9 alcohols are hexylene glycol, pentylene glycol, diethylene glycol monoethyl ether and butylene glycol; the weight ratio of the hexanediol to the pentanediol to the diethylene glycol monoethyl ether to the butanediol is (0.5-2): (0.3-1.5): (0.8-3): (0.6-5); preferably 1:1:1:1.

the hexanediol has a molecular weight of 118.2 and a flash point of 93 ℃ (open), specifically 1,2-hexanediol.

The pentanediol has a molecular weight of 104.2 and a flash point of 104 ℃ (open), specifically 1,2-pentanediol.

The molecular weight of the diethylene glycol monoethyl ether is 134.2, and the flash point is 96 ℃ (open).

The butanediol has a molecular weight of 90.1 and a flash point of 121 ℃ (open), specifically 1,3-butanediol.

In order to improve the formula compatibility of the nano-carrier and overcome the defects that 4-butyl resorcinol is difficult to dissolve in water, is easy to oxidize and discolor, and has irritation to skin and the like, the preparation method adopts the matching effect of hexanediol, pentanediol, diethylene glycol monoethyl ether and butanediol, effectively improves the dissolution degree of 4-butyl resorcinol in an aqueous medium, supposes that specific C2-C9 alcohol promotes the polarity of a carrier component and a solution medium to be kept close to the maximum extent, so that a stable saturated covalent bond is formed, the precipitation of 4-butyl resorcinol in a system is obviously inhibited, meanwhile, a micromolecular alcohol structure is matched with polyglycerol fatty acid ester to be wrapped on the surface of the 4-butyl resorcinol, a buffer protective layer is provided for the 4-butyl resorcinol, the temperature change and the negative influence of UV optical fiber irradiation on the 4-butyl resorcinol are reduced, and the high-temperature stability and the light sensitivity of the 4-butyl resorcinol in the nano-carrier are improved.

In some preferred embodiments, the polyglyceryl fatty acid ester comprises a combination of one or more of polyglyceryl-3 beeswax, polyglyceryl-6 polyricinoleate, polyglyceryl-10 oleate and polyglyceryl-6 caprylate.

Further preferably, the polyglycerin fatty acid ester includes polyglycerin-3 beeswax, polyglycerin-6 polyricinoleate, polyglycerin-10 oleate and polyglycerin-6 caprylate.

Still more preferably, the weight ratio of polyglycerol-3 beeswax, polyglycerol-6 polyricinoleate, polyglycerol-10 oleate and polyglycerol-6 caprylate is (1-3): (1-3): (1.5-4): (0.5-3); most preferably 2.5:2.5:2.5:2.

the invention unexpectedly discovers that the high-concentration retention of the nano-carrier in a target and a target cell can be improved by adopting the compounding action of the specific polyglycerol fatty acid ester, the slow-release and controlled-release actions are realized, the action time of active ingredients is prolonged, and the whitening effect of the nano-carrier is further improved; it was further found that when the weight ratio of polyglycerol-3 beeswax, polyglycerol-6 polyricinoleate, polyglycerol-10 oleate and polyglycerol-6 caprylate was (1-3): (1-3): (1.5-4): (0.5-3), the nano-carrier can simultaneously realize the obvious reduction of the melanin content and the obvious improvement of the apparent brightness under the extremely low dosage, thereby realizing the balance of low cost and high performance of the skin care product formula.

In some preferred embodiments, the vitamin derivative comprises a combination of one or more of 3-O-ethyl ascorbic acid, tocopherol acetate and nicotinamide, retinol palmitate, sodium ascorbyl phosphate, magnesium ascorbyl phosphate, ascorbyl glucoside, ascorbyl palmitate, tetrahexyldecyl ascorbate, ascorbyl methylsilanol pectate.

Further preferably, the vitamin derivatives include 3-O-ethyl ascorbic acid, tocopherol acetate and nicotinamide; the weight ratio of the 3-O-ethyl ascorbic acid, the tocopherol acetate and the nicotinamide is (4-10): (1-4): (6-15); preferably 7.5:2:10.

in some preferred embodiments, the emollient comprises a combination of one or more of caprylic/capric glycerate, isononyl isononanoate, polysilicone, palmitate, benzoate, stearate, triglyceride, myristate, squalane.

Further preferably, the emollient comprises caprylic/capric glycerate and isononyl isononanoate, the weight ratio of caprylic/capric glycerate to isononyl isononanoate is (0.5-3): 1; most preferably 1:1.

in some preferred embodiments, the weight ratio of 4-butylresorcinol, vitamin derivative, emollient is (5.5-10): (4-8): (2-6).

When applied to the skin, 4-butyl resorcinol has certain irritation to the skin, and limits the application of the 4-butyl resorcinol in skin care products. In the process of adjusting the formula, the applicant unexpectedly finds that when 3-O-ethyl ascorbic acid, tocopherol acetate and niacinamide are selected as vitamin derivatives, the weight ratio of the components is (0.5-3): 1, the caprylic/capric glycerate and isononyl isononanoate can obviously reduce the irritation of functional components to the skin, realize that the addition amount of 4-butyl resorcinol in the formula can reach more than 5 percent, and the skin is comfortable and has no stinging or allergic abnormal shape in the using process. Meanwhile, when the weight ratio of the 4-butyl resorcinol, the vitamin derivative and the emollient is (5.5-10): (4-8): and (2-6), the nano-carrier with finer particle size and higher co-transfusion efficiency can be formed, the action path of the product is not limited to epidermal cells and can deeply permeate to the basal layer of the dermis, and the cumulative skin permeation amount and retention rate of the nano-carrier are obviously higher than those of free active ingredients, so that the 'three enzymes one element' activity is deeply inhibited, the gene expression of pigment cells is reduced, and the multiple double skin care effects of whitening, skin moistening and stability maintenance are achieved.

In some preferred embodiments, the molecular structural formula of the anti-inflammatory agent is:

the anti-inflammatory agent is GCCS (carbenoxolone) with CAS number 471-53-4.

The second aspect of the invention provides a preparation method of a 4-butyl resorcinol co-delivery nano-carrier, wherein the preparation method of the 4-butyl resorcinol co-delivery nano-carrier comprises the following steps:

s1, adding 4-butyl resorcinol, a vitamin derivative, C2-C9 alcohol and a solvent into a reaction kettle A according to the formula amount, and uniformly mixing to obtain a material A;

s2, adding the softening agent, the anti-inflammatory agent and the polyglycerol fatty acid ester into a reaction kettle B according to the formula amount, and uniformly mixing to obtain a material B;

s3, adding the material B into the material A, and homogenizing at 1500-2000r/min for 1-5min to obtain a material C;

s4, adding the material C into a high-pressure micro-jet nano homogenizer, and carrying out stage type high-pressure micro-jet treatment to obtain a material D;

s5, filtering the material D, discharging and packaging to obtain a finished product of the 4-butylresorcinol co-conveyed nano carrier.

In some preferred embodiments, the step S4 is specifically: (1) Adding the material C into a high-pressure microjet nano homogenizer, carrying out 250-320MPa high-pressure microjet treatment on the material C, and collecting the material C1; (2) Carrying out 160-220MPa high-pressure microjet treatment on the C1 material to obtain a C2 material; (3) And carrying out 80-135MPa high-pressure micro-jet treatment on the C2 material to obtain a D material.

The applicant finds in the actual research and development process that 4-butyl resorcinol has good skin care effect, but generally has the defects of discoloration, tingling, water insolubility, slight cytotoxicity and the like, and influences the application and the effect of the 4-butyl resorcinol in the formula; compared with free 4-butyl resorcinol, the co-delivery nano carrier provided by the application adopts specific raw materials and process effects, can control the particle size distribution of a skin care product to be between 10 and 100nm, has a nano-grade particle size, and can rapidly penetrate through the stratum corneum of the skin to enter deep tissues; the retention property at the skin target part is good, the effect is durable, and the absorption rate of active factors can be effectively improved; the whitening active ingredients and the antioxidant ingredients act on a plurality of skin whitening targets to effectively control melanin sources; reduces the irritation of whitening activity to skin, and solves the problems of sensitivity of whitening components to light and heat, poor thermal stability, easy decomposition and discoloration of the whitening components under the action of light.

The invention provides an application of a 4-butyl resorcinol co-delivery nano-carrier in the field of skin care products.

In some preferred embodiments, the 4-butylresorcinol co-delivery nanocarriers are suitable for use in whitening, spot-removing, skin-lightening cream, milky lotion, essence, spray, mask, and the like. The universality of co-delivery nano-carriers is strong.

Further preferably, the 4-butyl resorcinol co-delivery nano-carrier is especially suitable for being used in essence products, and the addition amount can be as low as 0.5-5.0%.

Examples of the essence product include, but are not limited to, essence cream, essence lotion, and essence cream.

The existing 4-butyl resorcinol appears in more and more middle and high-end brand products, but on one hand, the price is extremely high, on the other hand, the 4-butyl resorcinol has poor solubility, poor temperature resistance and easy photolysis, and the bioavailability is very limited.

Has the beneficial effects that:

according to the application, active ingredients such as 4-butylresorcinol and the like are repeatedly encapsulated in the nanoemulsion with the particle size of 10-100nm through a nano-carrier targeted transmission technology, the obtained carrier enables whitening and skin-care ingredients to easily permeate into a skin dermis basal layer, and the effects of efficiently inhibiting melanin and brightening skin can be realized only by a very small amount of functional ingredients due to high targeting property and bioavailability. The co-delivery nano-carrier can effectively dissolve 4-butyl resorcinol, the compatibility and stability of the formula components are obviously improved, all indexes meet the safety technical specification of cosmetics, the cost performance of the product is extremely high, and the co-delivery nano-carrier is suitable for being widely popularized in the field of cosmetics.

Drawings

FIG. 1. Whitening efficacy test method of sample;

FIG. 2.1% concentration sample appearance results;

fig. 3.1% concentration sample L x value test results;

FIG. 4.1% concentration sample melanin content assay results;

FIG. 5363 apparent results for a sample of 5.3.5% concentration;

fig. 6.3.5% concentration sample L x value test results;

FIG. 7.3.5% concentration sample melanin content assay results;

FIG. 8.5% concentration sample apparent results;

fig. 9.5% concentration sample L x value test results;

FIG. 10.5% concentration sample results of melanin content measurements;

FIG. 11 shows the results of the heavy metal and microorganism contents measurements of example 1;

FIG. 12. Results of dioxane assay of example 1;

FIG. 13 shows the results of measuring diethylene glycol in example 1.

Detailed Description

Example 1.

The embodiment provides a 4-butyl resorcinol co-delivery nano-carrier, which comprises the following raw materials in percentage by weight: 7.5% of 4-butyl resorcinol, 10% of C2-C9 alcohol, 7% of polyglycerol fatty acid ester, 7% of vitamin derivative, 4% of emollient, 0.2% of anti-inflammatory agent and the balance of solvent.

The small molecular polyol is 1,2-hexanediol, 1,2-pentanediol, diethylene glycol monoethyl ether and 1,3-butanediol; 1,2-hexanediol, 1,2-pentanediol, diethylene glycol monoethyl ether and 1,3-butanediol in a weight ratio of 1:1:1:1.

the 1,2-hexanediol had a molecular weight of 118.2 and a flash point of 93 ℃ (open).

The 1,2-pentanediol had a molecular weight of 104.2 and a flash point of 104 ℃ (open).

The molecular weight of the diethylene glycol monoethyl ether is 134.2, and the flash point is 96 ℃ (open).

The 1,3-butanediol has a molecular weight of 90.1 and a flash point of 121 ℃ (open).

The polyglycerol fatty acid ester comprises polyglycerol-3 beeswax ester, polyglycerol-6 polyricinoleate, polyglycerol-10 oleate and polyglycerol-6 caprylate.

The weight ratio of the polyglycerol-3 beeswax ester to the polyglycerol-6 polyricinoleate ester to the polyglycerol-10 oleate to the polyglycerol-6 caprylate is 2.5:2.5:2.5:2.

the vitamin derivatives include 3-O-ethyl ascorbic acid, tocopherol acetate and nicotinamide; 3-O-ethyl ascorbic acid, tocopherol acetate and nicotinamide in a weight ratio of 7.5:2:10.

the emollient comprises caprylic/capric glycerate and isononyl isononanoate, and the weight ratio of the caprylic/capric glycerate to the isononyl isononanoate is 1:1.

the anti-inflammatory agent is GCCS (carbenoxolone), and the CAS number is 471-53-4; the structural formula is

The solvent is water.

In a second aspect, the present invention provides a method for preparing a 4-butyl resorcinol co-delivery nano-carrier, wherein the preparation method of the 4-butyl resorcinol co-delivery nano-carrier comprises the following steps:

s1, adding 4-butyl resorcinol, a vitamin derivative, C2-C9 alcohol and a solvent into a reaction kettle A according to the formula amount, and uniformly mixing at 80 ℃ to obtain a material A;

s2, adding the emollient, the anti-inflammatory agent and the polyglycerol fatty acid ester into a reaction kettle B according to the formula amount, and uniformly mixing at 80 ℃ to obtain a material B;

s3, adding the material B into the material A, and homogenizing at 1740r/min for 2min to obtain a material C;

s4, adding the material C into a high-pressure micro-jet nano homogenizer, and performing stage type high-pressure micro-jet treatment to obtain a material D;

s5, performing 200-mesh double-layer filtration on the material D, discharging and packaging to obtain a finished product of the 4-butylresorcinol co-conveyed nano carrier.

The step S4 specifically comprises the following steps: (1) Adding the material C into a high-pressure microjet nano homogenizer, carrying out 300MPa high-pressure microjet treatment on the material C, and collecting the material C1; (2) Carrying out 180MPa high-pressure microjet treatment on the C1 material to obtain a C2 material; (3) And (3) carrying out 100MPa high-pressure micro-jet treatment on the C2 material to obtain a D material.

Performance test method

1. In vitro whitening efficacy test

The whitening efficacy test was performed on samples of example 1 dissolved in water and formulated to 1wt%,3.5wt%,5 wt%.

The test method is shown in FIG. 1.

The test results at 1% are shown in FIGS. 2-4; the test results for the 3.5% sample are shown in FIGS. 5-7; the results of the 5% sample testing are shown in FIGS. 8-10.

2. Safety feature

(1) Heavy metal and microorganism content detection

The test result is shown in FIG. 11, and the test number is GZ210610019000922.

(2) Dioxane content detection

The test result is shown in figure 12 and the report number is 2021008923-2b, which is measured by the test analysis research institute of the academy of sciences of Guangdong province (the China Guangzhou analysis and test center, zhongguangdong for short).

(3) Diethylene glycol content detection

The test result is shown in FIG. 13 and the report number is 2021008924-8b, which is measured by the institute of analysis and analysis of the Guangdong academy of sciences (Guangzhou analysis and test center, china, for short, zhongguangdong test).

Claims (10)

1. The 4-butyl resorcinol co-delivery nano carrier is characterized by comprising the following raw materials in percentage by weight: 5-12% of 4-butyl resorcinol, 5-15% of C2-C9 alcohol, 4-10% of polyglycerol fatty acid ester, 2-10% of vitamin derivative, 1-15% of emollient, 0.01-2% of anti-inflammatory agent and the balance of solvent.

2. The 4-butyl resorcinol co-delivery nanocarrier of claim 1, wherein the C2-C9 alcohol comprises a combination of one or more of hexylene glycol, pentylene glycol, diethylene glycol monoethyl ether, butylene glycol, glycerol, sorbitol.

3. A 4-butyl resorcinol co-delivered nanocarrier according to claim 1 or 2, wherein the C2-C9 alcohol has a molecular weight of 85-142 and a flash point of 90-143 ℃.

4. A4-butylresorcinol co-delivery nanocarrier of any of claims 1-3, wherein the polyglycerol fatty acid ester comprises a combination of one or more of polyglycerol-3 beeswax, polyglycerol-6 polyricinoleate, polyglycerol-10 oleate and polyglycerol-6 caprylate.

5. The 4-butylresorcinol co-delivered nanocarrier of any of claims 1-4, wherein the vitamin derivatives comprise 3-O-ethyl ascorbic acid, tocopherol acetate and nicotinamide, retinol palmitate, sodium ascorbyl phosphate, magnesium ascorbyl phosphate, ascorbyl glucoside, ascorbyl palmitate, tetrahexyldecyl ascorbate, ascorbyl methylsilanol pectate in combination with one or more of them.

6. The 4-butyl resorcinol co-delivery nanocarrier of any of claims 1-5, wherein the emollient comprises a combination of one or more of caprylic/capric glycerate, isononyl isononanoate, polysilicone, palmitate, benzoate, stearate, triglyceride, myristate, squalane.

7. The 4-butyl resorcinol co-delivery nanocarrier of any of claims 1-6, wherein the weight ratio of 4-butyl resorcinol, vitamin derivative and emollient is (5.5-10): (4-8): (2-6).

8. The 4-butylresorcinol co-delivery nanocarrier of claim X, wherein the anti-inflammatory agent has the following molecular structure:

9. a4-butyl resorcinol co-delivered nanocarrier of claim X, wherein the preparation of the 4-butyl resorcinol co-delivered nanocarrier comprises:

s1, adding 4-butyl resorcinol, a vitamin derivative, C2-C9 alcohol and a solvent into a reaction kettle A according to the formula amount, and uniformly mixing to obtain a material A;

s2, adding the emollient, the anti-inflammatory agent and the polyglycerol fatty acid ester into a reaction kettle B according to the formula amount, and uniformly mixing to obtain a material B;

s3, adding the material B into the material A, and homogenizing at 1500-2000r/min for 1-5min to obtain a material C;

s4, adding the material C into a high-pressure micro-jet nano homogenizer, and performing stage type high-pressure micro-jet treatment to obtain a material D;

s5, filtering the material D, discharging and packaging to obtain a finished product of the 4-butylresorcinol co-conveyed nano carrier.

10. Use of the 4-butylresorcinol co-delivered nanocarrier of any of claims 1-9 in the field of skin care products.

Images