Microcapsule relieving stimulation of high-concentration vitamin c ethyl ether, preparation method therefor and use thereof

Abstract

A microcapsule relieving stimulation of high-concentration vitamin C ethyl ether, a preparation method therefor and the use thereof. The microcapsule capable of relieving stimulation of high-concentration vitamin C ethyl ether is successfully prepared via a complex coacervation microcapsule-encapsulating process, and meanwhile, the process creatively uses retinal as a curing cross-linking agent, which enhances stability of the microcapsules and unexpectedly achieves synergistic effects on whitening and antioxidant effects of vitamin C ethyl ether.

Description

Microcapsule for alleviating irritation caused by high-concentration vitamin C ethyl ether, and preparation method and use thereof

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of Chinese Application No. 202310806868.X, filed on July 4, 2023. Said application No. 202310806868.X is hereby incorporated by reference in its entirety. Technical Field

[0003] The present invention belongs to the technical field of cosmetics, and in particular relates to a microcapsule for alleviating the irritation of high-concentration vitamin C ethyl ether, and a preparation method and application thereof. Background Art

[0004] Vitamin C is one of nature's strongest antioxidants, capable of scavenging free radicals and protecting cellular tissues from damage caused by free radicals and reactive oxygen species. However, its applications are limited by its low lipophilicity, heat sensitivity, and inherent oxidative degradation. Consequently, numerous vitamin C derivatives have been developed to improve its performance.

[0005] Ascorbic acid ethyl ether is a new amphiphilic and lipophilic vitamin C derivative, allowing formulators to incorporate it into either the oil or water phase as needed. It is chemically very stable and does not discolor. This also allows for its addition at high or low temperatures, making it convenient for use. Furthermore, ascorbic acid ethyl ether readily penetrates the stratum corneum and enters the dermis. Once in the skin, it is readily broken down by enzymes, exerting the biological benefits of vitamin C and improving its bioavailability. Therefore, it can be used as an antioxidant and whitening agent in cosmetics. However, when the concentration of ascorbic acid ethyl ether in a cosmetic formula reaches 10%-20%, it can easily cause skin irritation, severely limiting its effectiveness and application range.

[0006] Microencapsulation technology refers to the use of natural or synthetic polymer materials to encapsulate dispersed solid particles, liquids, or gases to form tiny particles with semipermeable or sealed capsules. The encapsulation process is called microencapsulation, and the tiny particles formed are called microcapsules. Microcapsules have two basic components: the substance encapsulated within the microcapsule is called the core material, and the outer "shell" is called the wall material. During the preparation of the microcapsule, the wall material can isolate the core material from the external environment and then release the core material under appropriate conditions. Therefore, using microencapsulation technology to encapsulate the vitamin C ethyl ether raw material to alleviate and block the irritation caused by direct contact between vitamin C ethyl ether and the skin may be a good strategy to alleviate and resolve the skin irritation of vitamin C ethyl ether.

[0007] Traditional microcapsule preparation techniques include spray drying, supercritical fluid processing, and solvent diffusion. However, spray drying has certain temperature requirements for microcapsule preparation, which can cause structural changes in some heat-sensitive cosmetic active ingredients with whitening or antioxidant effects, thus limiting the application of spray drying. While supercritical fluid processing is environmentally friendly and avoids the use of organic solvents, the equipment is expensive, and the parameter control and structural modification technology is not yet mature, making it difficult to achieve large-scale industrial production. While the solvent diffusion method is simple and easy to prepare microcapsules, it also has the problem of organic solvent residue.

[0008] The complex coacervation method utilizes two oppositely charged polymers as composite capsule materials, disperses, suspends, or emulsifies the core material in an aqueous solution of the capsule material, and then crosslinks and coagulates with the core material under certain conditions to form capsules. The present invention successfully prepared microcapsules capable of mitigating the irritation of high-concentration vitamin C ethyl ether through a complex coacervation microencapsulation process. The innovative use of retinal as a curing crosslinking agent in this process not only enhances microcapsule stability but also unexpectedly synergizes with the whitening and antioxidant effects of vitamin C ethyl ether.

[0009] There is no report of relevant research results in the prior art.

[0010] Summary of the Invention

[0011] The purpose of the present invention is to fill the gap in the prior art, solve the problem of skin irritation caused by high-concentration vitamin C ethyl ether, and provide a microcapsule for alleviating the irritation caused by high-concentration vitamin C ethyl ether, as well as a preparation method and use thereof.

[0012] In order to achieve the purpose of the present invention, the present invention adopts the following technical solutions:

[0013] In a first aspect, the present invention provides a method for preparing microcapsules that alleviate the irritation of high-concentration vitamin C ethyl ether, the preparation method comprising the following steps:

[0014] (1) In 20-60 parts by weight of water, pre-dissolve 1-5 parts of sodium alginate, and then dissolve 0.5-5 parts of Tween-80, 0.5-5 parts of Span-80, and 0.5-5 parts of caprylic / capric triglyceride (GTCC) to form solution A;

[0015] (2) Dissolve 5-30 parts of vitamin C ethyl ether in 10-40 parts of water, and then disperse 0.2-2 parts of retinal to uniformly disperse them in the water to form solution B;

[0016] (3) Add 0.1-0.4 parts of acetic acid and 0.5-5 parts of chitosan to 10-40 parts of water to form solution C;

[0017] (4) Add solution B and solution C to solution A simultaneously at an appropriate dropwise addition rate, homogenizing at a speed of 8000-10000 rpm to form solution D;

[0018] (5) 10-40 parts of aqueous solution containing 0.5-5 parts of calcium chloride to form solution E;

[0019] (6) Solution E was added dropwise to solution D at an appropriate dropping speed, while homogenizing at a speed of 8000-10000 rpm to form microcapsules containing vitamin C ethyl ether and retinal.

[0020] As an optional manner, preferably, the preparation method comprises the following steps:

[0021] (1) In 40 parts by weight, pre-dissolve 1-5 parts of sodium alginate, then dissolve 1-2 parts of Tween-80, 1-2 parts of Span-80, and 1-2 parts of caprylic / capric triglyceride (GTCC) in 40 parts of water to form solution A;

[0022] (2) Dissolve 10-20 parts of vitamin C ethyl ether in 20 parts of water, and then disperse 0.5-1 part of retinal to form solution B.

[0023] (3) Add 0.2 parts of acetic acid and 1-2 parts of chitosan to 20 parts of water to form solution C;

[0024] (4) Add solution B and solution C to solution A simultaneously at an appropriate dropwise addition rate, homogenizing at a speed of 8000-9000 rpm to form solution D;

[0025] (5) In parts by weight, 20 parts of aqueous solution contain 1-2 parts of calcium chloride to form solution E;

[0026] (6) Solution E was added dropwise to solution D at an appropriate dropping speed, and homogenization was performed while adding the solution. The homogenization speed was 8000-9000 rpm to form microcapsules containing vitamin C ethyl ether and retinal.

[0027] As an optional manner, in the above preparation method, the dropping speed in step (4) and step (6) is 0.05 g / s.

[0028] In a second aspect, the present invention provides microcapsules for alleviating the irritation of high-concentration vitamin C ethyl ether, which are prepared by the preparation method described in the first aspect.

[0029] As an optional mode, in the above microcapsules, the microcapsules contain vitamin C ethyl ether and retinal.

[0030] As an optional method, in the above microcapsules, retinal is used as a cross-linking curing agent, and retinal has a synergistic effect on the whitening and antioxidant effects of vitamin C ethyl ether.

[0031] In a third aspect, the present invention provides use of the microcapsule described in the second aspect in preparing cosmetics with whitening and antioxidant effects.

[0032] As an optional mode, in the above use, the cosmetic is toner, lotion, essence, cream, ointment, facial mask or freeze-dried powder.

[0033] As an optional mode, in the above use, the content of the vitamin C ethyl ether in the cosmetic is 10-20% by weight.

[0034] Compared with the prior art, the present invention has the following beneficial effects:

[0035] The present invention successfully prepares microcapsules capable of alleviating the irritation of high-concentration vitamin C ethyl ether through a complex coacervation microencapsulation process. At the same time, retinal is creatively used as a curing cross-linking agent in the process. While enhancing the stability of the microcapsules, it is unexpectedly found that retinal has a synergistic effect on the whitening and antioxidant effects of vitamin C ethyl ether. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1: Schematic diagram of the microcapsule sample prepared in Example 1 and its microscope photograph (200x).

[0037] Figure 2: Color comparison of the microcapsule sample prepared in Example 1 (left) and the ordinary emulsion sample prepared in Example 2 (right) when both were irradiated with UV light for 10 minutes.

[0038] Figure 3: Comparison of GTCC release rates in two microcapsules.

[0039] Figure 4: Photos of the patch tester and experimental samples. The left image shows the VC Skin Rejuvenation Essence sample in the top row, and the Vitamin C Ethyl Ether Microcapsule sample in the bottom row. The right image shows the Vitamin C Ethyl Ether Microcapsule sample on the left, and the VC Skin Rejuvenation Essence sample on the right. DETAILED DESCRIPTION

[0040] The present invention will be further described below with reference to specific embodiments. It should be understood that the specific embodiments described herein are only used to illustrate the present invention and are not intended to limit the scope of the present invention.

[0041] If no specific techniques or conditions are specified in the examples, the experiments were carried out according to the techniques or conditions described in the literature in the field or according to the product instructions. If no manufacturer is specified for the reagents or instruments used, they are all conventional products that can be purchased through regular channels.

[0042] The experimental methods in the following examples are conventional methods unless otherwise specified. The experimental materials used in the following examples are commercially available products unless otherwise specified.

[0043] Example 1:

[0044] The present invention provides a method for preparing microcapsules capable of alleviating irritation caused by high-concentration vitamin C ethyl ether, the method comprising the following steps:

[0045] (1) Dissolve 2 parts of sodium alginate in 40 g of water, then dissolve 1 g of Tween-80, 1 g of Span-80, and 1 g of caprylic / capric triglyceride (GTCC) to form solution A.

[0046] (2) Dissolve 10 g of vitamin C ethyl ether in 20 g of water, and then disperse 0.5 g of retinal to form solution B.

[0047] (3) Add 0.2 g of acetic acid and 1 g of chitosan to 20 g of water to form solution C;

[0048] (4) Add solution B and solution C to solution A simultaneously at a dropwise addition rate of 0.05 g / s, homogenizing at a speed of 8000 rpm to form solution D;

[0049] (5) 1 g of calcium chloride is contained in 20 g of aqueous solution to form solution E;

[0050] (6) Solution E was added dropwise to solution D at a dropping speed of 0.05 g / s, and homogenization was performed while the solution was added. The homogenization speed was set at 8000 rpm to form microcapsules containing vitamin C ethyl ether and retinal.

[0051] A schematic diagram of the microcapsule sample prepared using the above method and its microscopic photograph are shown in Figure 1. The microscopic photograph in Figure 1 was obtained using an inverted fluorescence microscope with a magnification of 200x. As can be seen from the photograph, the microcapsules are uniform and stable, with no obvious adhesion between the microcapsules, and the average particle size of the microcapsules is approximately 10 μm.

[0052] Example 2:

[0053] A common emulsion containing vitamin C ethyl ether and retinal was prepared using the raw materials and dosage ratios in the microcapsule preparation process of Example 1.

[0054] The preparation method comprises the following steps:

[0055] (1) Add 1 g of sodium alginate and 10 g of vitamin C ethyl ether and dissolve them in 80 g of water to form an aqueous phase;

[0056] (2) Add 1 g of Tween-80, 1 g of Span-80, and 0.5 g of retinal and homogenize and dissolve them completely to form an oil phase;

[0057] (3) Add water to make the emulsion up to 100 g, and completely homogenize the aqueous phase and the oil phase to form an emulsion containing vitamin C ethyl ether and retinal.

[0058] Figure 2 shows a color comparison of the microcapsule sample prepared in Example 1 and the conventional emulsion sample prepared in Example 2, after simultaneous UV illumination for 10 minutes. The color changes of the two samples in the figure indicate that the microcapsule sample encapsulated with vitamin C ethyl ether exhibits significantly better stability than the emulsion sample containing vitamin C ethyl ether. The unencapsulated vitamin C ethyl ether emulsion undergoes a dramatic color change after UV illumination.

[0059] Example 3: In vitro release method to evaluate the cross-linking and curing effect of microcapsules

[0060] Microcapsules prepared according to the process of Example 1 and supplemented with retinal were labeled Sample A, and microcapsules prepared according to the process of Example 1 but using glutaraldehyde instead of retinal were labeled Sample B. GTCC was used as a calibrant in both Samples A and B, and the encapsulation rate was approximately 95%. Appropriate amounts of the microcapsule suspensions of Samples A and B were added to an aqueous solution containing polyethylene castor oil. The suspensions were shaken in a 40°C water bath at 10 rpm, removed periodically, and centrifuged at 3000 rpm for 3 minutes. 4 mL of the supernatant was collected and analyzed by liquid chromatography to calculate the cumulative GTCC release percentage. The results are shown in Figure 3.

[0061] The experimental results show that for sample A, cross-linked with retinal, only about 50% of the GTCC was released from the microcapsules after 1 hour of shaking. For sample B, cross-linked with glutaraldehyde, nearly 65% ​​of the GTCC was released from the microcapsules after 1 hour of shaking. This clearly shows that the cross-linking and curing of the microcapsules by retinal compensates for the vulnerability of the hydrogel microcapsule surface to external interference, further solidifying the outer surface of the microcapsules and reducing the release of GTCC encapsulated in the microcapsules.

[0062] Example 4: Experimental study on the whitening and antioxidant effects of the microcapsules of the present invention

[0063] 1.DPPH free radical scavenging experiment

[0064] The vitamin C ethyl ether microcapsule sample prepared in Example 1 was labeled as sample 1, sample 2 was prepared according to the concentration of vitamin C ethyl ether in the vitamin C ethyl ether sample, and sample 3 was prepared according to the ratio of retinal. The specific content details are shown in Table 1.

[0065] Table 1: Details of Vitamin C Ethyl Ether and Retinaldehyde Content in Samples 1-3

[0066] The prepared samples were mixed with DPPH (final concentration of 100 μM) and 8 replicate wells were set. At the same time, blank control wells without drug and Trolox positive control wells were set. The OD value was measured by microplate reader at 30°C for 1 h. The detection wavelength was 515 nm. The antioxidant rate was calculated according to the following formula. The results are shown in Table 2.

[0067] Antioxidant rate (%) = (1-OD 515nm / Blank hole OD 515nm )×100%

[0068] The details of the free radical scavenging rates of different samples are shown in Table 2 below.

[0069] Table 2: Free radical scavenging of samples 1-3

[0070] The free radical scavenging experimental data show that due to the co-existence of vitamin C ethyl ether and retinal in the microcapsules, the free radical scavenging efficiency is equivalent to that of the positive control. When there is only vitamin C ethyl ether, the free radical scavenging rate is average, while the free radical scavenging rate of the sample containing only retinal without vitamin C ethyl ether is poor. From the comprehensive data, the free radical scavenging effect of the vitamin C ethyl ether microcapsules cross-linked with retinal is the best.

[0071] 2. Tyrosinase Activity Inhibition Experiment

[0072] Tyrosinase catalyzes the conversion of the substrate tyrosine to dopaquinone, which then undergoes a series of reactions to ultimately produce melanin. The tyrosinase-catalyzed reaction is considered the rate-limiting step in melanin production, so substances that inhibit tyrosinase activity are considered to have potential whitening activity. Dopaquinone is a colored substance with a characteristic absorption peak at 470nm. The amount of dopaquinone produced is proportional to the activity of the enzyme. Therefore, the amount of dopaquinone produced in the system can be measured spectrophotometrically to reflect the enzyme's activity.

[0073] (1) Main reagents:

[0074] Tyrosinase (mushroom source) (Shanghai Yihe Biotechnology Co., Ltd., ≥500 U / mg); L-tyrosine (Aladdin, 99.0%-101.0%); α-arbutin (DSM, ≥98%); disodium hydrogen phosphate (Na2HPO4·12H2O) and sodium dihydrogen phosphate (NaH2PO4·2H2O) were all domestically produced analytical grade.

[0075] (2) Prepare samples according to the following combination:

[0076] Among them, samples No. 1, 2 and 3 are the same as the DPPH test sample numbers; the above three samples are diluted 8 times with phosphate buffer to obtain test samples.

[0077] (3) Experimental results:

[0078] The tyrosinase inhibition rates of the four test samples were compared, and the positive control was vitamin C. Table 3 shows the details of the tyrosinase inhibition rates of samples 1-3.

[0079] Table 3: Details of tyrosinase inhibition rates for samples 1-3

[0080] From the tyrosinase inhibition rate data of samples 1-3, it can be seen that the effect of vitamin C ethyl ether microcapsules is better than that of samples with vitamin C ethyl ether and retinal added separately. From the results, it can be seen that the microcapsule samples containing vitamin C ethyl ether and retinal have a significantly stronger effect in inhibiting tyrosinase than the samples with a single component.

[0081] Example 5: Antibacterial Experiment Test

[0082] In a zone of inhibition test (Bacillus subtilis), Staphylococcus aureus and Escherichia coli were tested. A certain amount of microcapsule solution was added dropwise to the center of a culture dish containing each of the bacteria. The culture was incubated under UV light and darkness for 18 hours, and the diameter of the zone of inhibition was observed and measured. While no antibacterial effect was observed with samples 2 and 3, the microcapsules of the present invention (sample 1) surprisingly exhibited some antibacterial activity (see Table 4).

[0083] Table 4: Antibacterial effect of vitamin C ethyl ether microcapsules containing retinal (sample No. 1)

[0084] The inventors believe that the reason why the microcapsules described in the present invention produce antibacterial effects is that retinal can react with the amino groups on the chitosan molecular chain to fix the position of the molecular chain and form a zipper-like hydrogen bond structure. However, chitosan has poor mechanical properties and has limitations when used alone as an antibacterial agent, especially it is easily degraded in acidic conditions. When it is cross-linked with retinal, retinal-cross-linked chitosan Schiff base can be obtained, which effectively improves its antibacterial durability and mechanical properties.

[0085] Example 6: Vitamin C ethyl ether microcapsule patch test of the present invention

[0086] Human skin patch test, usage method is based on: "Technical Specifications for Safety of Cosmetics" (2015 edition). General test method: Select a suitable patch tester, use the closed patch test method, select at least 30 qualified volunteers to participate in the test, and add the test substance, distilled water (deionized water) and control sample to the square chamber of the patch tester. Apply the patch tester with the test substance, distilled water (deionized water) and control sample to the inner side of the subject's forearm, and press it lightly with the palm of your hand to evenly apply it to the skin. Continue for 24 hours. Observe the skin reaction according to the standards in the table below 30 minutes (after the indentation disappears), 24 hours and 48 hours after removing the patch tester with the test substance, distilled water (deionized water) and control sample, and record the observation results.

[0087] In accordance with the patch test requirements of the "Technical Specifications for Safety of Cosmetics" (2015 edition), 0.03 grams of VC Rejuvenating Essence (a commercially available product of the applicant company, containing 10% vitamin C ethyl ether) were dripped into each cell of the upper row of the test patch device, and 0.03 grams of a vitamin C ethyl ether microcapsule sample were dripped into each cell of the lower row. The patches were then applied to the inner arm (see Figure 4, left). The two batches were tested for 24 and 48 hours, respectively. The skin reaction grading standards and test results are shown in Tables 5 and 6, respectively.

[0088] Table 5: Grading criteria for skin reactions to occlusive patch tests

[0089] Table 6: Skin occlusive patch test results

[0090] The results showed that the patch results of 5 people showed that the VC skin rejuvenation essence product was highly irritating, while the results of another 6 people showed that both test samples were non-irritating.

[0091] Example 7: Trial stimulation of vitamin C ethyl ether microcapsules of the present invention

[0092] Number of participants: 20. Trial Method: Each participant applied a sample of Vitamin C Ethyl Ether Microcapsules and a finished VC Whitening and Rejuvenating Essence to the front of their inner arm and behind their ear. After applying equal amounts of each sample, participants were asked to assess whether the samples produced any irritation, which manifested as a warming, stinging, or burning sensation, for approximately three minutes. The trial results are shown in Table 7.

[0093] Table 7: Stimulation test results of vitamin C ethyl ether microcapsules of the present invention

[0094] Example 8: Stability of Vitamin C Ethyl Ether Microcapsules of the Present Invention

[0095] The performance test results of the microcapsule samples obtained in Example 1 are shown in Table 8 below.

[0096] Table 8: Performance test results of vitamin C ethyl ether microcapsule samples of the present invention

[0097] As can be seen from the data in the above table, the microcapsule samples prepared in Example 1 have a uniform and stable appearance and remain stable under high and low temperature conditions without any delamination or rupture of the capsule. The pH value is weakly acidic, which meets the relevant standards of the cosmetics industry.

[0098] Obviously, those skilled in the art may make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if such changes and modifications fall within the scope of the claims and their equivalents, the present invention is intended to include such changes and modifications.

Claims

1. A method for preparing microcapsules for alleviating the stimulation of high concentration vitamin C ethyl ether, characterized in that: The preparation method comprises the following steps: (1) In 20-60 parts of water, 1-5 parts of sodium alginate are pre-dissolved, 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 solution A; (2) dissolving 5-30 parts of vitamin C ethyl ether in 10-40 parts of water, and then dispersing 0.2-2 parts of retinal, so that the retinal is uniformly dispersed in the water to form a solution B; (3) Add 0.1-0.4 parts of acetic acid and 0.5-5 parts of chitosan to 10-40 parts of water by weight to form solution C; (4) Add solution B and solution C to solution A at a suitable dropping speed, homogenizing at a speed of 8000-10000 rpm to form solution D; (5) In parts by weight, 10-40 parts of the aqueous solution contain 0.5-5 parts of calcium chloride to form solution E; (6) Solution E is added dropwise to solution D at an appropriate dropping speed, while homogenizing at a speed of 8000-10000 rpm to form microcapsules containing vitamin C ethyl ether and retinal.

2. The preparation method according to claim 1, characterized in that: The preparation method comprises the following steps: (1) In 40 parts of water, 1-5 parts of sodium alginate are pre-dissolved, 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 solution A; (2) Dissolve 10-20 parts of vitamin C ethyl ether in 20 parts of water, and then disperse 0.5-1 part of retinal to uniformly disperse them in the water to form solution B; (3) Add 0.2 parts of acetic acid and 1-2 parts of chitosan to 20 parts of water by weight to form solution C; (4) Add solution B and solution C to solution A at a suitable dropping speed, homogenizing at a speed of 8000-9000 rpm to form solution D; (5) In parts by weight, 20 parts of aqueous solution contain 1-2 parts of calcium chloride to form a solution E； (6) Solution E was added dropwise to solution D at an appropriate dropping speed, and homogenization was performed while the solution was added dropwise. The homogenization speed was 8000-9000 rpm to form microcapsules containing vitamin C ethyl ether and retinal.

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

4. Microcapsules for alleviating the irritation of high-concentration vitamin C ethyl ether prepared by the preparation method according to any one of claims 1 to 3.

5. The microcapsule according to claim 4, characterized in that: The microcapsule contains vitamin C ethyl ether and retinal.

6. The microcapsule according to claim 4 or claim 5, characterized in that: Retinal acts as a cross-linking curing agent, and retinal has a synergistic effect on the whitening and antioxidant effects of vitamin C ethyl ether.

7. Use of the microcapsule according to any one of claims 4 to 6 in preparing cosmetics with whitening and anti-oxidation effects.

8. The use according to claim 7, characterized in that: The cosmetics are toner, lotion, essence, cream, ointment, facial mask or freeze-dried powder.

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

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