CN115363973B - 4-butylresorcinol 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, 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 softener, 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 multiply packaged in nanoemulsion with particle size as low as 10-100nm through a nano-carrier targeting transmission technology, the obtained carrier enables whitening and skin care ingredients to permeate into skin dermis basal layers more easily, and high targeting property and bioavailability enable effects of inhibiting melanin and brightening skin color to be achieved with little functional ingredients.

Description

4-butylresorcinol 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 rise of aesthetic consciousness and consumption level of consumers, whitening has become a mainstream cosmetic function widely favored by the market. The whitening effect of the cosmetic on skin mainly depends on the functional components absorbed by the skin, and the whitening components on the market at present mainly concentrate on arbutin, vitamin C, derivatives, tranexamic acid and the like, and achieve the whitening effect by inhibiting pigmentation in the skin. However, these cosmetics still have the following problems: (1) The efficacy and the cost of the product are difficult to balance, the active ingredients of the skin care product with low cost are single, and the synergistic effect of various functional ingredients is lacked; the skin care product added with various functional components has higher price and is difficult to be received by market consumer groups; (2) The formula of the functional components has poor compatibility, poor environmental tolerance, difficulty in full dissolution in a system, high precipitation trend, poor thermal stability, easy decomposition and color change under illumination conditions, and incapability of long-term storage of products; (3) The bioavailability of the functional components is low, the functional components are difficult to penetrate through the deep skin structure to reach the target part, and the efficacy is difficult to fully exert; (4) The safety and the efficacy of the product are difficult to balance, and part of the efficacy components have obvious skin care effect, but are irritated to the skin, so that the problem of skin sensitivity is easy to cause, and the safety and the smoothness are difficult to be taken into consideration.

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

Disclosure of Invention

In order to solve the problems, the first aspect of 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 softener, 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, and can simultaneously load the functional components with different action mechanisms into the same nano-carrier, so that multi-level repair and protection are provided for skin, and on one hand, the multi-target is realized, the activity of polyphenol oxidase in the body is inhibited, and the formation and in-vivo deposition of melanin are inhibited; on one hand, the shedding of aged keratinocytes is limited, damaged lipid barriers are repaired, and skin resistance is improved; meanwhile, the production of inflammatory cytokines and cell mediators can be inhibited, the skin tolerance can be improved, and the skin immunity, antiallergic and antioxidant capacities can be regulated; it can also improve the dullness of skin, whiten skin, lighten color spots, improve uneven skin color, and reduce skin coloration caused by ultraviolet irradiation to skin.

In some preferred embodiments, the C2-C9 alcohol comprises 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 alcohol is hexanediol, pentanediol, diethylene glycol monoethyl ether, and butanediol; the weight ratio of the hexanediol, the pentanediol, the diethylene glycol monoethyl ether and 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 ℃ (opening), in particular 1, 2-hexanediol.

The molecular weight of the pentanediol is 104.2, and the flash point is 104 ℃ (opening), specifically 1, 2-pentanediol.

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

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

In order to improve the formula compatibility of the nano-carrier and solve the defects that 4-butyl resorcinol is indissolvable in water, easy to oxidize and easy to change color, has irritation to skin and the like, the application adopts the collocation effect of hexanediol, pentanediol, diethylene glycol monoethyl ether and butanediol to effectively improve the dissolution degree of 4-butyl resorcinol in an aqueous medium, and supposedly, a 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, thereby remarkably inhibiting the precipitation of 4-butyl resorcinol in a system, and simultaneously, a small molecular alcohol structure is matched with polyglycerol fatty acid ester to wrap the surface of 4-butyl resorcinol, so that a buffer protection layer is provided for the 4-butyl resorcinol, the temperature change is reduced, and the negative influence of the irradiation of UV optical fibers on the 4-butyl resorcinol is improved, so that the high-temperature stability and the photosensitivity 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 bee wax esters, polyglyceryl-6 polyricinoleate, polyglyceryl-10 oleate, and polyglyceryl-6 caprylate.

Further preferably, the polyglyceryl fatty acid ester comprises polyglyceryl-3 bee wax ester, polyglyceryl-6 polyricinoleate, polyglyceryl-10 oleate and polyglyceryl-6 caprylate.

Still more preferably, the weight ratio of polyglycerol-3 bee wax acid ester, 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.

according to the invention, the specific polyglycerol fatty acid ester compound effect is adopted, so that the high-concentration retention of the nano-carrier in the target and the target cells can be improved, the slow release and controlled release effects are realized, the action time of the active ingredient is prolonged, and the whitening effect of the nano-carrier is further improved; it was further found that when polyglycerin-3 bee wax acid ester, polyglycerin-6 polyricinoleate, polyglycerin-10 oleate and polyglycerin-6 caprylate were mixed in a weight ratio of (1-3): (1-3): (1.5-4): (0.5-3), the nano carrier can simultaneously realize the remarkable reduction of melanin content and the remarkable improvement of 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 3-O-ethyl ascorbic acid, tocopheryl acetate and niacinamide, retinol palmitate, sodium ascorbyl phosphate, magnesium ascorbyl phosphate, ascorbyl glucoside, ascorbyl palmitate, tetrahexyldecyl ascorbate, and a combination of one or more of ascorbyl methylsilanol pectate.

Further preferred, the vitamin derivatives include 3-O-ethyl ascorbic acid, tocopheryl acetate and niacinamide; 3-O-ethyl ascorbic acid, tocopheryl acetate and niacinamide in a weight ratio of (4-10): (1-4): (6-15); preferably 7.5:2:10.

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

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

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

4-butylresorcinol has a certain irritation to skin when applied to skin, limiting its application in skin care products. The applicant has unexpectedly found that, during the tuning of the formulation, when 3-O-ethyl ascorbic acid, tocopheryl acetate and niacinamide are chosen as vitamin derivatives, the compounding weight ratio is (0.5-3): 1 caprylic acid/capric acid glyceride and isononyl isononanoate, can obviously reduce the irritation of the functional components to the skin, and realizes that the addition amount of 4-butyl resorcinol in the formula can reach more than 5 percent, and the skin is comfortable without stinging or allergic isocratic in the use process. It was also found that when 4-butylresorcinol, vitamin derivative, and emollient were present in a weight ratio of (5.5-10): (4-8): and (2-6), the nano carrier with finer particle size and higher co-delivery efficiency can be formed, the acting path of the product is not only limited to epidermal cells, but also can deeply permeate into the basal layer of dermis, and the accumulated skin permeation and retention rate of the nano carrier are obviously higher than those of free active ingredients, so that the activity of 'three enzymes and one element' is deeply inhibited, the gene expression of pigment cells is reduced, and the multiple doubling skin care effects of whitening, moisturizing and maintaining are achieved.

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

the anti-inflammatory agent is GCCS (carbenoxolone), and CAS number is 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 steps of the 4-butyl resorcinol co-delivery nano-carrier comprise:

s1, adding 4-butylresorcinol, vitamin derivatives, 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 a softening agent, an anti-inflammatory agent and polyglycerol fatty acid ester into the 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 for 1-5min at 1500-2000r/min to obtain material C;

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

s5, filtering the material D, discharging and packaging to obtain the finished product of the 4-butyl resorcinol co-conveying nano-carrier.

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

In the actual research and development process, the applicant finds that although 4-butylresorcinol has better skin care effect, the defects of color change, stinging sensation, water insoluble property, slight cytotoxicity and the like commonly exist, so that the application and effect of the 4-butylresorcinol in a formula are affected; compared with free 4-butylresorcinol, the co-delivery nano carrier provided by the application adopts specific raw materials and process actions, can control the particle size distribution of skin care products to be between 10 and 100nm, has nano-scale particle size, and can quickly penetrate through skin stratum corneum to enter deep tissues; the retention at the skin target position is good, the effect is durable, and the absorptivity of the active factors can be effectively improved; the multiple whitening active ingredients and the antioxidant ingredients act on multiple skin whitening targets, so that melanin sources are effectively controlled; reduces the irritation of the whitening activity to the skin, and solves the problems of light sensitivity, heat sensitivity, poor thermal stability, easy decomposition and discoloration of the whitening component, and the like.

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

In some preferred embodiments, the 4-butylresorcinol co-delivery nanocarrier is suitable for use in products such as creams, lotions, essences, sprays, masks, etc. that whiten, remove spots, lighten skin, etc. The universality of co-delivery nano-carriers is strong.

Further preferably, the 4-butyl resorcinol co-delivery nanocarrier is particularly suitable for use in essence products, and the addition amount can be as low as 0.5-5.0%.

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

The existing 4-butyl resorcinol is more and more in medium-high-end brand products, but on one hand, the price is extremely high, on the other hand, the 4-butyl resorcinol is poor in solubility, poor in temperature resistance and easy to photolyze, and the biological utilization rate is extremely limited.

The beneficial effects are that:

according to the application, active ingredients such as 4-butylresorcinol and the like are multiply packaged in nanoemulsion with particle size as low as 10-100nm through a nano-carrier targeting transmission technology, the obtained carrier enables whitening and skin care ingredients to permeate into skin dermis basal layers more easily, and high targeting property and bioavailability enable effects of inhibiting melanin and brightening skin color to be achieved with little functional ingredients. The co-transportation nano carrier can effectively dissolve 4-butylresorcinol, the compatibility and stability of the formula components are obviously improved, various indexes meet the safety technical specification of cosmetics, the cost performance of the product is extremely high, and the method is suitable for being widely popularized in the field of cosmetics.

Drawings

FIG. 1. Method for testing whitening efficacy of samples;

FIG. 2.1% concentration sample apparent results;

fig. 3.1% concentration sample L-value detection results;

FIG. 4.1% concentration sample melanin content test results;

figure 5.3.5% concentration sample apparent results;

fig. 6.3.5% concentration sample detection results of L;

FIG. 7.3.5% concentration sample for melanin content measurement;

FIG. 8.5% concentration sample apparent results;

fig. 9.5% concentration sample L-value detection results;

FIG. 10.5% concentration sample melanin content test results;

FIG. 11 shows the results of the heavy metal and microorganism content test of example 1;

FIG. 12 shows the dioxane detection results of example 1;

FIG. 13 shows the diethylene glycol assay result of 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 polyalcohol 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 molecular weight of the 1, 2-hexanediol was 118.2 and the flash point was 93 ℃ (open).

The molecular weight of the 1, 2-pentanediol is 104.2, and the flash point is 104 ℃ (opening).

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

The molecular weight of the 1, 3-butanediol is 90.1, and the flash point is 121 ℃ (opening).

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

The weight ratio of the polyglycerol-3 bee wax acid ester to the polyglycerol-6 polyricinoleate 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, tocopheryl acetate and niacinamide; 3-O-ethyl ascorbic acid, tocopheryl acetate and niacinamide in a weight ratio of 7.5:2:10.

the softener comprises caprylic acid/capric acid glyceride and isononyl isononanoate, wherein the weight ratio of the caprylic acid/capric acid glyceride to the isononyl isononanoate is 1:1.

the anti-inflammatory agent is GCCS (carbenoxolone), and the CAS number is 471-53-4; the structure is as follows

The solvent is water.

The second aspect of the present embodiment provides a method for preparing a 4-butylresorcinol co-delivery nano-carrier, where the preparation steps of the 4-butylresorcinol co-delivery nano-carrier include:

s1, adding 4-butylresorcinol, vitamin derivatives, 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 a softening agent, an anti-inflammatory agent and polyglycerol fatty acid ester into the 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 for 2min at 1740r/min to obtain material C;

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

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

The step S4 specifically comprises the following steps: (1) Adding the material C into a high-pressure micro-jet nano homogenizer, carrying out 300MPa high-pressure micro-jet 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 carrying out 100MPa high-pressure microjet treatment on the C2 material to obtain the 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, configured to be 1wt%,3.5wt%,5 wt%.

The test method is shown in FIG. 1.

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

2. Safety of

(1) Heavy metal and microorganism content detection

The test was carried out by Guangzhou gold to detection technologies limited, the detection result is shown in fig. 11, and the test number is GZ210610019000922.

(2) Dioxane content detection

The test is carried out by the Guangdong national academy of sciences testing and analysis institute (China Guangzhou analysis and test center, short for middle and broad test), the detection result is shown in FIG. 12, and the report number is 2021008923-2b.

(3) Diethylene glycol content detection

The test is carried out by the Guangdong national academy of sciences testing and analysis institute (China Guangzhou analysis and test center, short for middle and broad test), the detection result is shown in FIG. 13, and report number is 2021008924-8b.

Claims (6)

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 derivatives, 1-15% of softening agent, 0.01-2% of anti-inflammatory agent and the balance of solvent;

the C2-C9 alcohol comprises one or more of hexanediol, pentanediol, diethylene glycol monoethyl ether, butanediol, glycerol and sorbitol;

the polyglyceryl fatty acid ester comprises one or more of polyglyceryl-3 bee wax acid ester, polyglyceryl-6 polyricinoleate, polyglyceryl-10 oleate and polyglyceryl-6 caprylate;

the vitamin derivatives include 3-O-ethyl ascorbic acid, tocopheryl acetate and niacinamide, retinol palmitate, sodium ascorbyl phosphate, magnesium ascorbyl phosphate, ascorbyl glucoside, ascorbyl palmitate, tetrahexyldecanol ascorbate, and ascorbyl methylsilanol pectate;

the molecular structural formula of the anti-inflammatory agent is as follows:

。

2. the 4-butylresorcinol co-delivery nanocarrier of claim 1, wherein the C2-C9 alcohol has a molecular weight of 85-142 and a flash point of 90-143 ℃.

3. A 4-butylresorcinol co-delivery nanocarrier according to claim 1, wherein the emollient comprises one or more of caprylic/capric glycerate, isononyl isononanoate, silicone, palmitate, benzoate, stearate, triglyceride, myristate, squalane in combination.

4. A 4-butylresorcinol co-delivery nanocarrier according to any of claims 1-3, wherein the weight ratio of 4-butylresorcinol, vitamin derivative, and emollient is (5.5-10): (4-8): (2-6).

5. A 4-butylresorcinol co-delivery nanocarrier according to claim 4, wherein the 4-butylresorcinol co-delivery nanocarrier is prepared by the steps of:

s1, adding 4-butylresorcinol, vitamin derivatives, 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 a softening agent, an anti-inflammatory agent and polyglycerol fatty acid ester into the 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 for 1-5min at 1500-2000r/min to obtain material C;

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

and S5, filtering the material D, discharging and packaging to obtain the finished product of the 4-butyl resorcinol co-conveying nano-carrier.

6. Use of the 4-butylresorcinol co-delivery nanocarrier of claim 1 in the preparation of a skin care product.

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