CN116531275A

CN116531275A - Microcapsule for relieving high-concentration vitamin C ethyl ether stimulation and preparation method and application thereof

Info

Publication number: CN116531275A
Application number: CN202310806868.XA
Authority: CN
Inventors: 姜燕飞
Original assignee: Beijing Qingyan Bozhi Health Management Co ltd
Current assignee: Beijing Qingyan Bozhi Health Management Co ltd; Shanghai Qingyan Boshi Biotechnology Co ltd
Priority date: 2023-07-04
Filing date: 2023-07-04
Publication date: 2023-08-04
Anticipated expiration: 2043-07-04
Also published as: CN116531275B

Abstract

The invention belongs to the technical field of cosmetics, and particularly relates to a microcapsule for relieving high-concentration vitamin C ethyl ether stimulation, and a preparation method and application thereof. The microcapsule capable of relieving the stimulation of high-concentration vitamin C ethyl ether is successfully prepared through a complex coacervation microcapsule wrapping process, and meanwhile, the retinol is creatively used as a curing cross-linking agent in the process, so that the stability of the microcapsule is enhanced, and meanwhile, the synergistic effect of the retinol on the whitening and antioxidation effects of the vitamin C ethyl ether is unexpectedly discovered.

Description

Microcapsule for relieving high-concentration vitamin C ethyl ether stimulation and preparation method and application thereof

Technical Field

The invention belongs to the technical field of cosmetics, and particularly relates to a microcapsule for relieving high-concentration vitamin C ethyl ether stimulation, and a preparation method and application thereof.

Background

Vitamin C is one of the strongest antioxidants in nature, and can capture free radicals, protect cell tissues and resist damage caused by free radicals and active oxygen substances. Vitamin C has limited applications due to its low lipophilicity, thermal sensitivity, and autooxidative degradation. Thus, a number of vitamin C derivatives have been developed to improve their properties.

Vitamin C ethyl ether is a new lipophilic hydrophilic amphoteric vitamin C derivative, which allows formulators to add the vitamin C derivative into an oil phase or a water phase according to needs, is very stable on chemical substances, is a vitamin C derivative without color change, and also allows vitamin C ethyl ether to be added at high temperature or low temperature, so that the use is convenient. In addition, the vitamin C ethyl ether easily penetrates through the skin cuticle layer in the formula and enters the dermis layer, and is easily decomposed by biological enzyme after entering the skin to exert the biological effect of the vitamin C, so that the bioavailability of the vitamin C ethyl ether is improved, and the vitamin C ethyl ether can be used as an anti-aging agent and a whitening agent in cosmetics. However, when the concentration of vitamin C ethyl ether in the cosmetic formulation reaches 10% -20%, irritation to skin is easily generated, which severely limits the use effect and application range of vitamin C ethyl ether.

The microcapsule coating technology refers to a technology of coating dispersed solid particles, liquid or gas substances with natural or synthetic polymer materials to form tiny particles with semipermeable or sealed capsule membranes. The process in which encapsulation is called microencapsulation, and the tiny particles formed are called microcapsules. The microcapsules have two basic components, the substance enclosed within the microcapsules being called the core material, and the outer "shell" being called the wall material. In the preparation of the microcapsules, the wall material isolates the core material from the environment and then releases the core material under appropriate conditions. Therefore, the vitamin C ethyl ether raw material is subjected to encapsulation treatment by utilizing the microcapsule encapsulation technology, so that the irritation phenomenon caused by the direct contact of the vitamin C ethyl ether and the skin is relieved and blocked, and the vitamin C ethyl ether is possibly a good strategy for relieving and solving the skin irritation of the vitamin C ethyl ether.

The conventional microcapsule preparation technology includes spray drying, supercritical fluid, solvent diffusion, etc. However, the spray drying process requires a certain temperature for preparing the microcapsules, which may cause structural changes in some cosmetic active ingredients having whitening or antioxidation effects, which are sensitive to heat, so that the application range of the spray drying process is limited. The supercritical fluid method for preparing the microcapsule is environment-friendly, and can avoid the use of organic solvents, but equipment is expensive, and the parameter control and structure transformation technology is not mature, so that the industrial mass production is difficult to realize. The solvent diffusion method for preparing the microcapsule has the advantages of simple and convenient process and easy emptying, but has the problem of organic solvent residue.

The complex coacervation method is a method in which two polymer materials having opposite charges are used as a composite capsule material, and a core material is dispersed, suspended or emulsified in an aqueous solution of the capsule material, crosslinked under certain conditions, and coagulated with the core material to form a capsule. The microcapsule capable of relieving the stimulation of high-concentration vitamin C ethyl ether is successfully prepared through a complex coacervation microcapsule wrapping process, and meanwhile, the retinol is creatively used as a curing cross-linking agent in the process, so that the stability of the microcapsule is enhanced, and meanwhile, the synergistic effect of the retinol on the whitening and antioxidation effects of the vitamin C ethyl ether is unexpectedly discovered.

There is no report on related research results in the prior art.

Disclosure of Invention

The invention aims to fill the blank of the prior art, solve the problem of skin irritation of high-concentration vitamin C ethyl ether, and provide a microcapsule for relieving the irritation of the high-concentration vitamin C ethyl ether, and a preparation method and application thereof.

In order to achieve the purpose of the invention, the invention adopts the following technical scheme:

in a first aspect, the present invention provides a method of preparing microcapsules for alleviating stimulation by high concentrations of vitamin C ethyl ether, the method comprising the steps of:

(1) According to parts by weight, 1-5 parts of sodium alginate is pre-dissolved in 20-60 parts of water, and then 0.5-5 parts of tween-80, 0.5-5 parts of span-80 and 0.5-5 parts of caprylic capric triglyceride (GTCC) are dissolved to form a solution A;

(2) According to the weight portions, 5 to 30 portions of vitamin C ethyl ether are dissolved in 10 to 40 portions of water, and 0.2 to 2 portions of retinol are dispersed again, so that the retinol is uniformly dispersed in the water to form a solution B;

(3) Adding 0.1-0.4 part of acetic acid into 10-40 parts of water, and adding 0.5-5 parts of chitosan to form a solution C;

(4) Adding the solution B and the solution C into the solution A at proper dropping speed, and homogenizing while adding dropwise to form a solution D at 8000-10000 rpm;

(5) 10-40 parts by weight of aqueous solution contains 0.5-5 parts by weight of calcium chloride to form solution E;

(6) Dropping solution E into solution D at proper dropping speed, homogenizing while dropping, and forming microcapsule containing vitamin C ethyl ether and retinaldehyde at homogenizing speed of 8000-10000 rpm.

Alternatively, preferably, the preparation method includes the steps of:

(1) According to parts by weight, 1-5 parts of sodium alginate is pre-dissolved in 40 parts of water, and then 1-2 parts of tween-80, 1-2 parts of span-80 and 1-2 parts of caprylic/capric triglyceride (GTCC) are dissolved to form a solution A;

(2) According to the weight parts, 10-20 parts of vitamin C ethyl ether is dissolved in 20 parts of water, and 0.5-1 part of retinol is dispersed again, so that the retinol is uniformly dispersed in the water to form a solution B;

(3) Adding 0.2 part of acetic acid and 1-2 parts of chitosan into 20 parts of water by weight to form a solution C;

(4) Adding the solution B and the solution C into the solution A at proper dropping speed, and homogenizing while adding dropwise, wherein the homogenizing speed is 8000-9000 rpm to form a solution D;

(5) The 20 parts of aqueous solution contains 1-2 parts of calcium chloride to form a solution E;

(6) Solution E was added dropwise to solution D at an appropriate dropping rate while homogenizing at 8000-9000 rpm to form microcapsules containing vitamin C ethyl ether and retinaldehyde.

Alternatively, in the above production method, the drop acceleration in the step (4) and the step (6) is 0.05 g/s.

In a second aspect, the present invention provides microcapsules prepared by the method of the first aspect described above that alleviate the irritation of high concentrations of vitamin C ethyl ether.

Alternatively, in the above microcapsule, the microcapsule contains vitamin C ethyl ether and retinaldehyde.

Alternatively, in the microcapsules described above, retinaldehyde is used as a crosslinking curing agent, and the retinaldehyde produces a synergistic effect on the whitening and antioxidant effects of vitamin C ethyl ether.

In a third aspect, the present invention provides the use of the microcapsule according to the second aspect above for preparing a cosmetic having whitening and antioxidant effects.

Alternatively, in the above use, the cosmetic is a toner, an emulsion, an essence, a cream, a paste, a mask or a lyophilized powder.

Alternatively, in the above use, the content of the vitamin C ethyl ether in the cosmetic is 10 to 20% by weight.

Compared with the prior art, the invention has the following beneficial effects:

the microcapsule capable of relieving the stimulation of high-concentration vitamin C ethyl ether is successfully prepared through a complex coacervation microcapsule wrapping process, and meanwhile, the retinol is creatively used as a curing cross-linking agent in the process, so that the stability of the microcapsule is enhanced, and meanwhile, the synergistic effect of the retinol on the whitening and antioxidation effects of the vitamin C ethyl ether is unexpectedly discovered.

Drawings

Fig. 1: schematic representation of microcapsule sample prepared in example 1 and its microscopic photograph (200×).

Fig. 2: color contrast plots for both the microcapsule sample prepared in example 1 (left side) and the normal emulsion sample prepared in example 2 (right side) under UV light irradiation for 10 minutes.

Fig. 3: comparison of GTCC release rate in both microcapsules.

Fig. 4: patch test tester patch photographs and experimental sample photographs. Wherein, the upper row of the left graph is a VC skin care essence sample, and the lower row is a vitamin C ethyl ether microcapsule sample. The left side of the right graph is a vitamin C ethyl ether microcapsule sample, and the right side is a VC skin care essence sample.

Detailed Description

The invention will be further illustrated with reference to specific examples. It should be understood that the detailed description and specific examples are intended for purposes of illustration only and are not intended to limit the scope of the invention.

The specific techniques or conditions are not identified in the examples and are described in the literature in this field or are carried out in accordance with the product specifications. The reagents or equipment used were conventional products available for purchase through regular channels, with no manufacturer noted.

The experimental methods in the following examples are conventional methods unless otherwise specified. The test materials used in the examples described below, unless otherwise specified, are all commercially available products.

Example 1:

the invention relates to a preparation method of microcapsules for relieving high-concentration vitamin C ethyl ether stimulation, which comprises the following steps:

(1) Pre-dissolving 2 parts of sodium alginate in 40 g of water, and dissolving 1 g of tween-80, 1 g of span-80 and 1 g of caprylic capric triglyceride (GTCC) to form a solution A;

(2) Dissolving 10 g of vitamin C ethyl ether in 20 g of water, and redispersing 0.5 g of retinaldehyde to uniformly disperse the retinaldehyde in the water to form a solution B;

(3) Adding 0.2 g of acetic acid into 20 g of water, and adding 1 g of chitosan to form a solution C;

(4) Dropwise adding the solution B and the solution C into the solution A at the speed of 0.05 g/s, homogenizing while dropwise adding, and forming a solution D at the homogenizing speed of 8000 rpm;

(5) 20 g of the aqueous solution contains 1 g of calcium chloride to form a solution E;

(6) Solution E was added dropwise to solution D at a drop rate of 0.05 g/s while homogenizing at 8000 rpm to form microcapsules containing vitamin C ethyl ether and retinaldehyde.

A schematic diagram of the microcapsule sample prepared by the method and a photo under a microscope thereof are shown in FIG. 1. The photograph under the microscope in FIG. 1 is obtained by using a fluorescence inverted microscope, the magnification is 200 times, and as can be seen from the photograph, the microcapsule state is uniform and stable, no obvious adhesion exists between the microcapsules, and the average particle diameter of the microcapsules is about 10 μm.

Example 2:

a common emulsion containing vitamin C ethyl ether and retinaldehyde was prepared using the raw materials and the amount ratio in the microcapsule preparation process in example 1.

The preparation method comprises the following steps:

(1) Adding 1 g of sodium alginate and 10 g of vitamin C ethyl ether into 80 g of water to form a water phase;

(2) Adding 1 g of Tween-80, 1 g of span-80 and 0.5 g of retinaldehyde, and homogenizing and dissolving to form an oil phase completely;

(3) Make-up water to 100 grams of emulsion, the aqueous and oil phases are homogenized to complete an emulsion comprising vitamin C ethyl ether and retinaldehyde.

A color comparison chart of the microcapsule sample prepared in example 1 and the normal emulsion sample prepared in example 2 under UV light irradiation for 10 minutes at the same time is shown in fig. 2. As can be seen from the color changes of the two samples in the figure, the stability of the microcapsule sample coated with the vitamin C ethyl ether is obviously better than that of the emulsion sample containing the vitamin C ethyl ether, and the vitamin C ethyl ether emulsion which is not coated with the microcapsule sample is obviously subjected to severe color change reaction after UV irradiation.

Example 3: in vitro release method for evaluating crosslinking and curing effects of microcapsules

The microcapsules prepared according to the procedure of example 1 with added retinaldehyde were labeled as sample a and the microcapsules prepared according to the procedure of example 1 with glutaraldehyde instead of retinaldehyde were labeled as sample B; in the sample A and the sample B, GTCC is used as a calibration object, and the wrapping rate is about 95%; and respectively taking a proper amount of microcapsule suspension of the sample A and a proper amount of microcapsule suspension of the sample B, adding the microcapsule suspension into an aqueous solution containing polyethylene castor oil, respectively placing the aqueous solution into a water bath shaking table at 40 ℃ for 10 r/min for shaking, taking out the aqueous solution at regular time, centrifuging the aqueous solution at 3000 r/min for 3min, respectively taking supernatant fluid 4 mL, carrying out content detection by using a liquid chromatograph, and calculating the GTCC cumulative release percentage. The results are shown in FIG. 3.

From the experimental results, the sample A is a sample crosslinked by using the retinoid, and only about 50% of GTCC is finally dissociated into microcapsules after being subjected to shaking table treatment for 1 hour; sample B was glutaraldehyde crosslinked and subjected to shaking for 1 hour to obtain GTCC with almost 65% final free microcapsules; the microcapsule is obviously cured by the crosslinking of the retinol, so that the defect that the surface of the hydrogel microcapsule is easily interfered by the outside is overcome, the outer surface of the microcapsule is cured more, and the release of GTCC (gtCC) wrapped in the microcapsule is reduced.

Example 4: whitening and antioxidant efficacy experiment of the microcapsule

1. DPPH free radical scavenging experiments

Sample 1 was labeled with the vitamin C ethyl ether microcapsule prepared in example 1, sample 2 was prepared according to the concentration of vitamin C ethyl ether in the vitamin C ethyl ether sample, sample 3 was prepared according to the ratio of retinaldehyde, and details of specific contents are shown in Table 1.

Table 1: details of the vitamin C ethyl ether and retinaldehyde content in samples 1-3

The prepared sample was mixed with DPPH (final concentration: 100 mM), 8 replicate wells were set, and a blank control well and a Trolox positive control well were set without drug, at 30 ℃,1 h, and the OD value was measured by an enzyme-labeled instrument, the detection wavelength was 515 nm, and the antioxidant ratio was calculated according to the following formula, and the results are shown in table 2.

Antioxidant rate (%) = (1-experimental well OD) _{515 nm} Blank well OD _{515 nm} ）×100%

The details of the radical scavenging rate of the different samples are shown in table 2 below.

Table 2: free radical scavenging case for samples 1-3

As can be seen from the experimental data of scavenging free radicals, the scavenging free radical efficiency of the microcapsule is equivalent to that of a positive control because of the coexistence of vitamin C ethyl ether and retinaldehyde, the scavenging free radical efficiency of the microcapsule is generally similar to that of a positive control, and the scavenging free radical efficiency of the vitamin C ethyl ether-free sample is poor when the vitamin C ethyl ether-free sample contains only retinaldehyde, so that the scavenging free radical efficiency of the vitamin C ethyl ether microcapsule crosslinked by retinaldehyde is best from the comprehensive data.

2. Tyrosinase activity inhibition assay

Tyrosinase can catalyze substrate tyrosine to generate dopaquinone, and then melanin is finally generated through a series of reactions, and the tyrosinase catalytic reaction is regarded as a speed limiting step of melanin generation, so that substances with tyrosinase activity inhibition are regarded as potential whitening activity. The dopaquinone is a colored substance, has a characteristic absorption peak under 470 and nm, and the generation amount of the dopaquinone is directly proportional to the activity of the enzyme, so that the generation amount of the dopaquinone in a system can be measured by a spectrophotometer to reflect the activity of the enzyme.

(1) The main reagent comprises:

tyrosinase (mushroom source) (Shanghai England Biotech Co., ltd. Gtoreq.500U/mg); l-tyrosine (aledine, 99.0% -101.0%); alpha-arbutin (DSM, > 98%); disodium hydrogen phosphate (Na) ₂ HPO ₄ •12H ₂ O), sodium dihydrogen phosphate (NaH) ₂ PO ₄ •2H ₂ O) is all the homemade analytical purity.

(2) Samples were prepared as follows:

wherein, the numbers of the samples 1, 2 and 3 are consistent with the number of the DPPH sample; the three samples are diluted by 8 times by phosphate buffer solution respectively to obtain test samples.

(3) Experimental results:

and (3) testing and comparing the tyrosinase inhibition rates of the four test samples, wherein the positive control is vitamin C. Table 3 shows the tyrosinase inhibition rate details of samples 1-3.

Table 3: details of tyrosinase inhibition rates of sample Nos. 1-3

From the tyrosinase inhibition rate data of samples 1-3, the effect of the vitamin C ethyl ether microcapsule is better than that of the vitamin C ethyl ether and retinaldehyde samples which are added independently, and from the results, the effect of the microcapsule samples containing the vitamin C ethyl ether and the retinaldehyde on inhibiting tyrosinase is obviously stronger than that of the samples with single components.

Example 5: antibacterial test

The bacteria to be tested are staphylococcus aureus and escherichia coli by adopting a bacteriostasis zone experiment (Bacillus subtilis), a certain amount of microcapsule solution is dripped into the center of a culture dish of each bacteria, 18 h is cultivated under the conditions of ultraviolet light and darkness, and the diameter of the bacteriostasis zone is observed and measured. No. 2 and No. 3 samples were used for dripping respectively, and the microcapsule (No. 1 sample) of the present invention also unexpectedly produced a certain antibacterial effect (see Table 4).

Table 4: antibacterial effect of retinoid-containing vitamin C ethyl ether microcapsule (sample No. 1)

The inventor believes that the reason why the microcapsule of the invention generates the antibacterial effect is that the retinol can react with amino groups on chitosan molecular chains to fix the positions of the molecular chains and form a zipper-shaped hydrogen bond structure, and the mechanical property of chitosan is poor, and the chitosan is limited when being singly used as an antibacterial agent, and is easy to degrade in particular in acidity, and when the retinol is crosslinked with the retinol, the retinol crosslinked chitosan Schiff base can be obtained, so that the antibacterial durability and the mechanical property of the chitosan Schiff base are effectively improved.

Example 6: the vitamin C ethyl ether microcapsule spot-pasting test

The human skin patch test method is based on the following steps: cosmetic safety Specification (2015 edition). The general test method comprises the following steps: at least 30 qualified volunteers were selected to participate in the test by the closed patch test method by selecting an appropriate patch test tester, and the test object, distilled water (deionized water) and the control sample were added to the square chamber of the patch test tester. The patch test tester with the test substance, distilled water (deionized water) and the control sample was applied to the inner side of the forearm of the subject, and was uniformly applied to the skin by lightly pressing with the palm for 24. 24 h, and skin reactions were observed 30 minutes after removing the patch test tester with the test substance, distilled water (deionized water) and the control sample (after the indentation disappeared), 24. 24 h and 48. 48 h according to the following table standards, respectively, and the observation results were recorded.

According to the requirements of spot pasting experiments in cosmetic safety technical Specification (2015 edition), 0.03 g of VC skin care essence product (the product sold on the market by applicant company and 10% of vitamin C ethyl ether in the formula) is respectively dripped into each row in the spot pasting device to be tested, the next row is respectively dripped with 0.03 g of vitamin C ethyl ether microcapsule sample, and the samples are pasted on the inner side of an arm (see left diagram of fig. 4), and the two tests are respectively 24 hours and 48 hours. The skin reaction grading criteria and experimental results are shown in tables 5 and 6, respectively.

Table 5: skin response grading standard for skin closed patch test

Table 6: experimental results of skin closed patch

The results show that: the patch results of 5 persons show that the VC skin tendering essence product has strong irritation, and the 6 persons show that the two tested samples have no irritation.

Example 7: the vitamin C ethyl ether microcapsule stimulus test method of the invention

Trial number: 20 persons. The trial mode is as follows: each person respectively smears a vitamin C ethyl ether microcapsule sample and a VC whitening and skin-tendering essence finished product at the front part of the inner side of the arm and behind the ear, and perceives whether the sample has a stimulating sense or not after the same amount of sample is smeared for about 3 minutes, wherein the specific stimulating sense is shown as fever, stinging or burning sense. The test results of the subjects are shown in table 7.

Table 7: results of the vitamin C ethyl ether microcapsule stimulation trial of the invention

Example 8: stability of vitamin C ethyl ether microcapsules of the present invention

The results of performance measurements of the microcapsule samples obtained in example 1 are shown in Table 8 below.

Table 8: performance detection result of vitamin C ethyl ether microcapsule sample

As can be seen from the data in the table, the microcapsule sample prepared in example 1 has uniform and stable appearance, is still stable under the conditions of high temperature and low temperature, and does not have any phenomena of layering, capsule breaking and the like; the pH value shows weak acidity and accords with the relevant standards of the cosmetic industry.

It will be apparent to those skilled in the art that various modifications and variations can be made to the present invention without departing from the spirit or scope of the invention. Thus, it is intended that the present invention also include such modifications and alterations insofar as they come within the scope of the appended claims or the equivalents thereof.

Claims

1. A preparation method of microcapsules for relieving high-concentration vitamin C ethyl ether stimulation is characterized by comprising the following steps of: the preparation method comprises the following steps:

2. The method of manufacturing according to claim 1, characterized in that: the preparation method comprises the following steps:

3. The preparation method according to claim 2, characterized in that: the drop acceleration in step (4) and step (6) was 0.05 g/s.

4. Microcapsules prepared by the method of any one of claims 1 to 3 that alleviate high concentration vitamin C ethyl ether irritation.

5. The microcapsule according to claim 4, wherein: the microcapsule contains vitamin C ethyl ether and retinaldehyde.

6. The microcapsule according to claim 4 or claim 5, wherein: retinaldehyde is used as a crosslinking curing agent, and the retinaldehyde has a synergistic effect on the whitening and antioxidation effects of vitamin C ethyl ether.

7. Use of the microcapsule according to any one of claims 4 to 6 for preparing a cosmetic having whitening and antioxidant effects.

8. Use according to claim 7, characterized in that: the cosmetic is toner, emulsion, essence, cream, ointment, facial mask or freeze-dried powder.

9. Use according to claim 7 or claim 8, characterized in that: the content of the vitamin C ethyl ether in the cosmetic is 10-20% by weight percent.