High-content and high-stability quercetin anti-wrinkle composition and application

Abstract

The invention discloses a quercetin anti-wrinkle composition with high content and high stability and application. The composition is prepared from the quercetin, the 4-tert-butyl cyclohexanol and the isopropyl lauroyl sarcosinate. Compared with the prior art, the oily composition of 4-tert-butyl cyclohexanol, isopropyl lauroyl sarcosinate and quercetin is constructed, the problem that quercetin is difficult to dissolve can be effectively solved, and the application convenience of quercetin is greatly improved; the content of quercetin in the composition is high, and the composition has a certain anti-wrinkle effect; the 4-tert-butyl cyclohexanol and the isopropyl lauroyl sarcosinate have a synergistic effect on the dissolution of the quercetin; the composition can be used for preparing quercetin microemulsion after being compounded with other grease, and has extremely high stability. Therefore, the method has important application value in the field of cosmetics.

Description

Technical Field

[0001] The invention belongs to the technical field of cosmetics, and particularly relates to a high-content, high-stability quercetin anti-wrinkle composition and application thereof. Background Art

[0002] Quercetin is a natural flavonoid compound with strong biological activity. It is widely found in various fruits and vegetables. It has antioxidant, anti-cancer, antiviral, antibacterial, and anti-inflammatory effects, and plays an important role in the clinical treatment of cancer and cardiovascular diseases. However, quercetin has poor water solubility, poor oil solubility, chemical instability, and low bioavailability, which greatly limits its application. It is reported that the solubility of quercetin in water is only 0.01 mg / mL (25°C), the solubility in DMSO is 150 mg / mL (25°C), and the solubility in ethanol is 4.0 mg / mL (37°C); the industry generally uses delivery systems to improve its stability, efficacy, and bioavailability. Common delivery methods include liposome encapsulation, cyclodextrin encapsulation, supramolecular cocrystals, etc.

[0003] The patent application number 202310059574.5, "An antibacterial and acne-removing microemulsion containing plant extracts and its preparation method", mentions a quercetin microemulsion system, in which the quercetin content is 0-1.7% of the mixture B (camellia oil, Tween 85, co-surfactant), which is relatively low, and the co-surfactant used is ethanol, 1,2-propylene glycol and other highly irritating polyols; similarly, the patent application number 202310059662.5, "A camellia oil microemulsion loaded with quercetin and camellia saponin and its preparation method", contains only 0.51%-1.1% quercetin; the solubility of quercetin in camellia oil is less than 1 mg / g, and the surfactant used in the microemulsion system is Tween 85, and the co-surfactants used are ethanol and propylene glycol; therefore, a stable quercetin oily composition is very important, which can get rid of the restrictions on surfactants and co-surfactants and expand the application range of quercetin. Summary of the invention

[0004] The purpose of the present invention is to provide a high-content, high-stability quercetin anti-wrinkle composition and application in view of the characteristics of quercetin being poorly soluble in water and oil and having poor stability. 4-tert-butyl cyclohexanol is a specific TRPV1 antagonist, and has been proven by human tests to effectively block the burning or tingling sensation caused by capsaicin, thereby effectively relieving skin discomfort; therefore, 4-tert-butyl cyclohexanol is generally used as a soothing ingredient in the field of cosmetics, and the amount added is very low; in the process of studying the quercetin dissolution system, the present invention found that the combination of 4-tert-butyl cyclohexanol and isopropyl lauroyl sarcosinate can significantly improve the solubility of quercetin, which has never been reported before; based on this, the present invention constructs an oily composition with a high quercetin content and examines its application potential in the field of cosmetics.

[0005] The objective of the present invention is achieved through the following technical solutions:

[0006] The invention relates to a quercetin composition, which comprises quercetin, 4-tert-butylcyclohexanol and isopropyl lauroyl sarcosinate.

[0007] As one embodiment of the present invention, quercetin, 4-tert-butyl cyclohexanol and isopropyl lauroyl sarcosinate are heated until quercetin and 4-tert-butyl cyclohexanol are dissolved, thereby obtaining the quercetin composition.

[0008] As an embodiment of the present invention, there is no precipitation of quercetin in the quercetin composition. Based on 1 part by weight of quercetin, the amount of 4-tert-butyl cyclohexanol and lauroyl sarcosine isopropyl ester can be any amount that makes the quercetin in the quercetin composition not precipitate. The no precipitation also includes no precipitation when standing at 0°C-normal temperature. In the system of the present invention, the addition of 4-tert-butyl cyclohexanol allows the system to achieve effective dissolution of quercetin with less lauroyl sarcosine isopropyl ester.

[0009] As an embodiment of the present invention, in the composition, the mass ratio of quercetin, 4-tert-butyl cyclohexanol and isopropyl lauroyl sarcosinate is 1:1:4-40.

[0010] As an embodiment of the present invention, in the composition, the mass ratio of quercetin, 4-tert-butyl cyclohexanol and isopropyl lauroyl sarcosinate is 1:0.5:6-40.

[0011] As an embodiment of the present invention, in the composition, the mass ratio of quercetin, 4-tert-butyl cyclohexanol and isopropyl lauroyl sarcosinate is 1:1.5:3.5-40.

[0012] As an embodiment of the present invention, in the composition, the solubility of quercetin is 0.5% to 17%.

[0013] As an embodiment of the present invention, in the composition, the solubility of quercetin is 2.3% to 16.7%.

[0014] The present invention also relates to a use of the above-mentioned quercetin composition in preparing medicines or cosmetics.

[0015] As an embodiment of the present invention, the cosmetic comprises an antioxidant, anti-inflammatory or anti-wrinkle cosmetic.

[0016] As an embodiment of the present invention, quercetin is at least one of the active ingredients in the drug.

[0017] As an embodiment of the present invention, the drug is an antioxidant, anticancer, antiviral, antibacterial or anti-inflammatory drug.

[0018] As an embodiment of the present invention, the quercetin composition is used as a cosmetic raw material in the form of a dosage form such as liposomes or microemulsions. In the field of cosmetics, within a certain concentration range, the higher the quercetin content, the better the anti-wrinkle effect. Quercetin is generally made into dosage forms such as liposomes and microemulsions, and enters the cosmetic development in the form of cosmetic raw materials; in systems such as microemulsions, the volume of the internal phase is an important factor affecting the particle size of the system; under the same particle size, the volume of the internal phase is determined; therefore, the higher the quercetin content in the composition, the greater the active substance load in the microemulsion, and the lower the effective concentration of the microemulsion. From the perspective of cosmetic development, the lower the effective concentration of the quercetin microemulsion, the lower the formula cost and the higher the economic value.

[0019] In summary, the present invention constructs an oily composition of 4-tert-butyl cyclohexanol, isopropyl lauroyl sarcosinate, and quercetin, which has the characteristics of high quercetin content and high stability, and has important application value in the field of cosmetics. Compared with the prior art, the present invention has the following beneficial effects:

[0020] 1) Effectively solve the problem of quercetin dissolution difficulty and greatly improve its application convenience;

[0021] 2) The composition has a high content of quercetin and has certain anti-wrinkle effects.

[0022] 3) 4-tert-butyl cyclohexanol and isopropyl lauroyl sarcosinate have a synergistic effect on quercetin dissolution;

[0023] 4) The composition can be used for the preparation of quercetin microemulsion after being compounded with other oils and fats, and has extremely high stability. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Other features, objects and advantages of the present invention will become more apparent from the detailed description of non-limiting embodiments made with reference to the following drawings:

[0025] Figure 1 This is the particle size distribution diagram of the quercetin microemulsion in Application Example 1. DETAILED DESCRIPTION

[0026] The present invention is further illustrated by the following examples, but any example or combination thereof should not be construed as limiting the scope or implementation of the present invention. Without departing from the spirit and scope of the present invention, those skilled in the art may make any modifications or changes to the technical solution of the present invention, and such modifications and changes are also included in the scope of the present invention.

[0027] In the examples, if the specific conditions are not specified, the conditions are carried out according to normal conditions or the conditions recommended by the manufacturer. If the manufacturer is not specified for all reagents or instruments, they are all conventional products that can be purchased commercially. In order to better illustrate the present invention, numerous specific details are provided in the specific embodiments below. It should be understood by those skilled in the art that the present invention can be implemented equally without certain specific details. In other embodiments, methods, means, equipment and steps well known to those skilled in the art are not described in detail to highlight the gist of the present invention.

[0028] Example 1

[0029] Add 0.5g of quercetin, 0.5g of 4-tert-butyl cyclohexanol, and 20g of lauroyl sarcosine isopropyl ester into a beaker, heat and stir until dissolved evenly; cool to room temperature to obtain a brown-yellow transparent liquid, and stand at 3°C ​​for 24h without precipitation; at this time, the ratio of quercetin: 4-tert-butyl cyclohexanol: lauroyl sarcosine isopropyl ester is 1:1:40.

[0030] Example 2

[0031] Add 0.5g of quercetin, 0.5g of 4-tert-butyl cyclohexanol, and 10g of lauroyl sarcosine isopropyl ester into a beaker, heat and stir until dissolved evenly; cool to room temperature to obtain a brown-yellow transparent liquid, and stand at 3°C ​​for 24h without precipitation; at this time, the ratio of quercetin: 4-tert-butyl cyclohexanol: lauroyl sarcosine isopropyl ester is 1:1:20.

[0032] Example 3

[0033] Add 0.5g quercetin, 0.5g 4-tert-butyl cyclohexanol, and 5g lauroyl sarcosine isopropyl ester into a beaker, heat and stir until dissolved evenly; cool to room temperature to obtain a brown-yellow transparent liquid, and stand at 3°C ​​for 24h without precipitation; at this time, the ratio of quercetin: 4-tert-butyl cyclohexanol: lauroyl sarcosine isopropyl ester is 1:1:10.

[0034] Example 4

[0035] Add 0.5g quercetin, 0.5g 4-tert-butyl cyclohexanol, and 3g lauroyl sarcosine isopropyl ester into a beaker, heat and stir until dissolved evenly; cool to room temperature to obtain a brown-yellow transparent liquid, and stand at 3°C ​​for 24h without precipitation; at this time, the ratio of quercetin: 4-tert-butyl cyclohexanol: lauroyl sarcosine isopropyl ester is 1:1:6.

[0036] Example 5

[0037] Add 0.5g quercetin, 0.5g 4-tert-butyl cyclohexanol, and 2g lauroyl sarcosine isopropyl ester into a beaker, heat and stir until dissolved evenly; cool to room temperature to obtain a brown-yellow transparent liquid, and stand at 3°C ​​for 24h without precipitation; at this time, the ratio of quercetin: 4-tert-butyl cyclohexanol: lauroyl sarcosine isopropyl ester is 1:1:4.

[0038] Example 6

[0039] 0.5g quercetin, 0.5g 4-tert-butyl cyclohexanol, and 1.5g lauroyl sarcosine isopropyl ester were added to a beaker, and the mixture could not be completely dissolved after heating and stirring, and the solution was turbid and opaque; at this time, the ratio of quercetin: 4-tert-butyl cyclohexanol: lauroyl sarcosine isopropyl ester was 1:1:3. Compared with Examples 1-5, when the addition amounts of quercetin and 4-tert-butyl cyclohexanol were 1 part each, lauroyl sarcosine isopropyl ester needed to be added at least 4 parts to make the system transparent, and quercetin had no precipitation.

[0040] Example 7

[0041] Add 0.5g quercetin, 0.25g 4-tert-butyl cyclohexanol, and 3g lauroyl sarcosine isopropyl ester into a beaker, heat and stir until dissolved evenly; cool to room temperature to obtain a brown-yellow transparent liquid, and stand at 3°C ​​for 24h without precipitation; at this time, the ratio of quercetin: 4-tert-butyl cyclohexanol: lauroyl sarcosine isopropyl ester is 1:0.5:6.

[0042] Example 8

[0043] 0.5g quercetin, 0.25g 4-tert-butyl cyclohexanol, and 2g lauroyl sarcosine isopropyl ester were added to a beaker, and the solution was not completely dissolved after heating and stirring, and the solution was turbid and opaque; at this time, the ratio of quercetin: 4-tert-butyl cyclohexanol: lauroyl sarcosine isopropyl ester was 1: 0.5: 4. Compared with Example 7, it can be seen that when the addition amounts of quercetin and 4-tert-butyl cyclohexanol were 1 part and 0.5 part, lauroyl sarcosine isopropyl ester needed to add at least 6 parts to make the system transparent, and quercetin had no precipitation; compared with Example 5, it can be seen that in the system of the present invention (containing lauroyl sarcosine isopropyl ester), the addition amount of 4-tert-butyl cyclohexanol will affect the stability of the system, and the higher the addition amount, the greater the solubility of the system to quercetin. It should also be noted that the melting point of 4-tert-butyl cyclohexanol is 62-70°C. If isopropyl lauroyl sarcosinate is added alone, the system will be solid, not liquid, when cooled.

[0044] Example 9

[0045] Add 0.5g quercetin, 0.75g 4-tert-butyl cyclohexanol, and 2g lauroyl sarcosine isopropyl ester into a beaker, heat and stir until dissolved evenly; cool to room temperature to obtain a brown-yellow transparent liquid, and stand at 3°C ​​for 24h without precipitation; at this time, the ratio of quercetin:4-tert-butyl cyclohexanol:lauroyl sarcosine isopropyl ester is 1:1.5:4.

[0046] Example 10

[0047] Add 0.5g quercetin, 0.75g 4-tert-butyl cyclohexanol, and 1.75g ​​lauroyl sarcosine isopropyl ester into a beaker, heat and stir until dissolved evenly; cool to room temperature to obtain a brown-yellow transparent liquid, and stand at 3°C ​​for 24h without precipitation; at this time, the ratio of quercetin: 4-tert-butyl cyclohexanol: lauroyl sarcosine isopropyl ester is 1:1.5:3.5.

[0048] Embodiment 11

[0049] 0.5g quercetin, 0.75g 4-tert-butyl cyclohexanol, and 1.5g lauroyl sarcosine isopropyl ester were added to a beaker, and the mixture could not be completely dissolved after heating and stirring, and the solution was turbid and opaque; at this time, the ratio of quercetin: 4-tert-butyl cyclohexanol: lauroyl sarcosine isopropyl ester was 1: 1.5: 3. Compared with Example 10, when the addition amounts of quercetin and 4-tert-butyl cyclohexanol were 1 part and 1.5 parts, lauroyl sarcosine isopropyl ester needed to be added at least 3.5 parts to make the system transparent, and quercetin had no precipitation.

[0050] Comparative Example 1

[0051] 0.5g of quercetin and 3.0g of isopropyl lauroyl sarcosinate were added to a beaker. After heating and stirring, the solution could not be completely dissolved and was turbid and opaque. At this time, the ratio of quercetin: 4-tert-butyl cyclohexanol: isopropyl lauroyl sarcosinate was 1:0:6. Compared with Example 4 and Example 7, it can be clearly seen that 4-tert-butyl cyclohexanol has a synergistic effect on the system and is better than single isopropyl lauroyl sarcosinate.

[0052] Comparative Example 2

[0053] 0.5g of quercetin and 4.0g of isopropyl lauroyl sarcosinate were added to a beaker, heated and stirred until uniformly dissolved; cooled to room temperature, it was a brown-yellow transparent liquid, and there was no precipitation after standing at 3°C ​​for 24 hours; at this time, the ratio of quercetin: 4-tert-butyl cyclohexanol: isopropyl lauroyl sarcosinate was 1:0:8. Compared with Example 5, Example 7, and Comparative Example 1, it can be seen that the addition of 4-tert-butyl cyclohexanol allows the system to effectively dissolve quercetin with less isopropyl lauroyl sarcosinate.

[0054] Comparative Example 3

[0055] 0.5g of quercetin and 10g of ethylhexylglycerol were added to a beaker. After heating and stirring, they could not be completely dissolved, and the solution was turbid and opaque. At this time, the ratio of quercetin: 4-tert-butyl cyclohexanol: ethylhexylglycerol was 1:0:10; compared with Example 3 and Comparative Example 2, it can be seen that ethylhexylglycerol is not enough to achieve effective dissolution of quercetin, which indirectly confirms the superiority of the lauroyl sarcosine isopropyl ester and 4-tert-butyl cyclohexanol system.

[0056] Comparative Example 4

[0057] 0.5g of quercetin and 5g of diisopropyl adipate were added to a beaker. After heating and stirring, they could not be completely dissolved, and the solution was turbid and opaque. At this time, the ratio of quercetin: 4-tert-butyl cyclohexanol: diisopropyl adipate was 1:0:10; compared with Example 3 and Comparative Example 2, it can be seen that diisopropyl adipate is not enough to achieve effective dissolution of quercetin, which indirectly confirms the superiority of the lauroyl sarcosine isopropyl ester and 4-tert-butyl cyclohexanol system.

[0058] Comparative Example 5

[0059] 0.5g of quercetin and 5g of phenylpropanol were added to a beaker. After heating and stirring, the solution could not be completely dissolved, and the solution was turbid and opaque. At this time, the ratio of quercetin: 4-tert-butylcyclohexanol: phenylpropanol was 1:0:10; compared with Example 3 and Comparative Example 2, it can be seen that phenylpropanol is not sufficient to achieve effective dissolution of quercetin, which indirectly confirms the superiority of the lauroyl sarcosine isopropyl ester and 4-tert-butylcyclohexanol system.

[0060] Application Examples

[0061] Referring to the low-temperature emulsification method in the patent "A microemulsion and its preparation method" with application number 202211695584.X, quercetin, isopropyl lauroyl sarcosinate, 4-tert-butyl cyclohexanol system and tocopherol acetate and other oils are compounded and used in the preparation of microemulsion. The detailed process is as follows:

[0062] Weigh 2g of quercetin, 2g of 4-tert-butyl cyclohexanol, 16g of isopropyl lauroyl sarcosinate, and 4g of tocopherol acetate in a 100mL beaker, heat and stir until dissolved evenly, and record it as the oil phase; weigh 20g of PPG-13-decyltetradecanol polyether-24 and 24g of glycerol, add them to a 150mL beaker, start mechanical stirring, and stir at 300rpm for 10min until uniform; then add the oil phase to the beaker in three batches, stir for 30min until uniform, and obtain a microemulsion premix; then add the microemulsion premix into 32g of water, stir the generated gel blocks evenly to obtain a microemulsion, and the microemulsion is clear and transparent and there is no precipitation after centrifugation at 9000rpm for 10min.

[0063] The particle size was measured using a Bettersize 3000 particle size analyzer. Figure 1 , the average particle size D50 is 84nm; and its one-month stability under different conditions is investigated, as shown in Table 1 below; From Table 1, it can be seen that the content of quercetin in the microemulsion under light conditions is reduced by 12.6%, and the content of quercetin in the sample under other conditions is almost unchanged, which shows that the stability of this quercetin microemulsion is very good and has great application potential in the field of cosmetics. It should be noted that this application example is to illustrate the application value of the composition in the field of cosmetics, specifically in the field of microemulsion. In addition, in this application example, if 2g quercetin, 16g lauroyl sarcosine isopropyl ester, and 4g tocopherol acetate are used for operation, quercetin will precipitate under this ratio.

[0064] Table 1 Quercetin content in samples after one month of investigation

[0065] project -18℃ 3℃ 40℃ 48℃ High and low temperature cycle illumination Room temperature Quercetin Content 2.083 2.099 2.014 2.022 2.014 1.748 1.958

[0066] Efficacy test case

[0067] The solution of Example 3 was used as a sample to test its anti-wrinkle effect, as follows:

[0068] Skin fibroblasts in the logarithmic growth phase were inoculated into a 3 cm diameter cell culture dish or a 6-well cell culture plate. After the cells were fused to 80%, the sample group was cultured with culture medium of different concentrations of samples, and the blank control well was added with normal culture medium. The culture was continued for 24 hours, and the cell supernatant was collected. The content of type I collagen was detected by ELISA kit.

[0069] Table 2 Collagen promotion test results

[0070] Product Name concentration Relative value of type I collagen Remark Normal control / 100.00％ Blank control TGF 50ng / ml 143.87％ Positive Control Oily composition 0.01％ 117.27％ sample

[0071] As can be seen from Table 2, the oily composition of 4-tert-butyl cyclohexanol, isopropyl lauroyl sarcosinate and quercetin has a significant promoting effect on type I collagen and has a certain anti-wrinkle effect.

[0072] The above describes the specific embodiments of the present invention. It should be understood that the present invention is not limited to the above specific embodiments, and those skilled in the art may make various modifications or variations within the scope of the claims, which do not affect the essence of the present invention.

Claims

1. A quercetin composition comprising quercetin, 4-tert-butylcyclohexanol and isopropyl lauroyl sarcosinate.

2. The quercetin composition according to claim 1, characterized in that The quercetin composition is obtained by heating quercetin, 4-tert-butyl cyclohexanol and isopropyl lauroyl sarcosinate until the quercetin and 4-tert-butyl cyclohexanol are dissolved.

3. The quercetin composition according to claim 1, characterized in that In the composition, the mass ratio of quercetin, 4-tert-butyl cyclohexanol and isopropyl lauroyl sarcosinate is 1:1:4-40.

4. The quercetin composition according to claim 1, characterized in that In the composition, the mass ratio of quercetin, 4-tert-butyl cyclohexanol and isopropyl lauroyl sarcosinate is 1:0.5:6-40.

5. The quercetin composition according to claim 1, characterized in that In the composition, the mass ratio of quercetin, 4-tert-butyl cyclohexanol and isopropyl lauroyl sarcosinate is 1:1.5:3.5-40.

6. The quercetin composition according to claim 1, characterized in that In the composition, the solubility of quercetin is 0.5% to 17%.

7. The quercetin composition according to claim 1, characterized in that In the composition, the solubility of quercetin is 2.3% to 16.7%.

8. Use of the quercetin composition according to any one of claims 1 to 7 in the preparation of medicines or cosmetics.

9. The use according to claim 8, characterized in that The quercetin composition is used as a cosmetic raw material in the form of liposome or microemulsion dosage form.

10. The use according to claim 8, characterized in that The cosmetics include anti-oxidant, anti-inflammatory or anti-wrinkle cosmetics.

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