Nanoemulsion compositions, their preparation methods and applications

Abstract

This invention relates to a nanoemulsion composition, its preparation method, and its application. The nanoemulsion composition comprises 30 wt% to 88 wt% of oil, 10 wt% to 45 wt% of emulsifier, 1 wt% to 10 wt% of silymarin, and 1 wt% to 20 wt% of retinoids. The emulsifier is selected from polysorbate and polyoxyethylene hydrogenated castor oil, and the LogP value of the oil is less than or equal to 5. The nanoemulsion composition provided by this invention, under the action of a specific emulsifier, simultaneously encapsulates silymarin and retinoids through the oil, effectively improving the solubility and stability of silymarin and retinoids. When added to water, it can self-emulsify to form a stable nanoemulsion system, thereby increasing the content, utilization rate, and skin permeability of silymarin in cosmetics. Simultaneously, the nanoemulsion composition does not contain alcohol or polyols or other co-emulsifiers, has low skin irritation, and is generally applicable to different types of cosmetic systems, showing broad application prospects.

Description

Technical Field

[0001] This invention relates to the field of cosmetic technology, and in particular to a nanoemulsion composition, its preparation method, and its application. Background Technology

[0002] Self-emulsifying nanoemulsion carrier systems are anhydrous homogeneous solid or liquid nanoemulsion compositions consisting of active substances, an oil phase, emulsifiers, and co-emulsifiers. When in contact with water, they can spontaneously form an oil-in-water nanoemulsion of approximately 10 nm to 150 nm by stirring or shaking at room temperature. They are characterized by ease of use and good permeability.

[0003] Silymarin is a general term for a large class of flavonoid lignan compounds. It has excellent antioxidant properties and also has anti-radiation, moisturizing and anti-wrinkle, and anti-aging effects. It is often used as an active substance in cosmetics and other fields. However, silymarin is difficult to dissolve in water and common organic solvents and has poor oil solubility. There are many problems with using silymarin in self-emulsifying nanoemulsion carrier systems: (1) Although adding a large amount of alcohol, polyol or surfactant as a co-emulsifier can improve the solubility of silymarin to a certain extent, these large amounts of co-emulsifiers are irritating to human skin and may cause skin allergies or contact dermatitis when used in cosmetics; (2) In nanoemulsions containing polyol co-emulsifiers, silymarin has great instability and is prone to layering or precipitation; (3) When used in cosmetics, the content and utilization rate of silymarin are very low, and it is difficult to penetrate the skin to achieve excellent effects. Summary of the Invention

[0004] Therefore, it is necessary to provide a nanoemulsion composition, its preparation method, and its application to address the above-mentioned problems. The nanoemulsion composition not only greatly improves the solubility and stability of silymarin, thereby increasing the content, utilization rate, and skin permeability of silymarin in cosmetics, but also does not contain alcohol or polyols or other emulsifiers, thus having less skin irritation and broad application prospects.

[0005] The present invention provides a nanoemulsion composition comprising 30 wt% to 88 wt% of oil, 10 wt% to 45 wt% of emulsifier, 1 wt% to 10 wt% of silymarin and 1 wt% to 20 wt% of retinoids, wherein the emulsifier is selected from polysorbate and polyoxyethylene hydrogenated castor oil, and the LogP value of the oil is less than or equal to 5.

[0006] In one embodiment, the mass ratio of the polysorbate to the polyoxyethylene hydrogenated castor oil is 1:1 to 4:3.

[0007] In one embodiment, the polysorbate is selected from at least one of polysorbate-20, polysorbate-60, or polysorbate-80;

[0008] And / or, the polyoxyethylene hydrogenated castor oil is selected from at least one of PEG-40 hydrogenated castor oil or PEG-60 hydrogenated castor oil.

[0009] In one embodiment, the retinoid is selected from at least one of retinol, retinol derivatives, or psoralen.

[0010] In one embodiment, the oil is selected from at least one of lauroyl sarcosine isopropyl ester or propylene glycol octanoate.

[0011] In one embodiment, when the oil is selected from lauroyl sarcosine isopropyl ester and propylene glycol octanoate, the mass ratio of lauroyl sarcosine isopropyl ester to propylene glycol octanoate is greater than 1:1.

[0012] In one embodiment, the oil content in the nanoemulsion composition is 40% to 60% by mass;

[0013] And / or, in the nanoemulsion composition, the mass fraction of the emulsifier is 15% to 40%;

[0014] And / or, the mass ratio of silymarin to retinoid is 1:0.1 to 1:10.

[0015] The present invention also provides a method for preparing the nanoemulsion composition as described above, comprising the following steps:

[0016] The oil, emulsifier, and silymarin are mixed to obtain a mixed solution;

[0017] The nanoemulsion composition is obtained by dissolving retinoids in the mixed solution.

[0018] In one embodiment, the temperature is 75°C to 95°C during the step of mixing the oil, emulsifier and silymarin.

[0019] And / or, in the step of dissolving retinoids in the mixed solution, the temperature is 50°C to 60°C.

[0020] The present invention also provides the application of the nanoemulsion composition as described above in cosmetics.

[0021] In the above-mentioned nanoemulsion composition, on the one hand, through the synergistic emulsification effect of polysorbate and polyoxyethylene hydrogenated castor oil, as well as the coating effect of oil, the solubility and stability of silymarin and retinoids are significantly improved and the skin irritation is reduced without the presence of alcohol or polyols or other co-emulsifiers in the nanoemulsion composition system. On the other hand, retinoids can act as a co-emulsifier to further enhance the solubility of silymarin. At the same time, silymarin also helps to inhibit the oxidation of retinoids, further improving the stability of retinoids.

[0022] Therefore, the nanoemulsion composition of the present invention effectively improves the solubility and stability of silymarin and retinoids. When added to water, it self-emulsifies to form a stable nanoemulsion system, thereby increasing the content, utilization rate, and skin permeability of silymarin in cosmetics. This achieves antioxidant, moisturizing, anti-wrinkle, and anti-aging effects. Simultaneously, it does not contain alcohol or polyols or other emulsifiers, resulting in less skin irritation and promoting skin health, especially suitable for sensitive skin. Furthermore, the nanoemulsion composition has a simple preparation process, is easy to use, and is universally applicable to different types of cosmetic systems, showing broad application prospects. Detailed Implementation

[0023] To facilitate understanding of the present invention, it will be described in more detail below. However, it should be understood that the present invention can be implemented in many different forms and is not limited to the embodiments or examples described herein. Rather, these embodiments or examples are provided to make the disclosure of the present invention more thorough and complete.

[0024] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used herein in the specification of this invention is for the purpose of describing particular embodiments or examples only and is not intended to limit the invention. The optional scope of the term "and / or" as used herein includes any one of two or more of the related listed items, as well as any and all combinations of the related listed items, including any two related listed items, any more related listed items, or a combination of all related listed items.

[0025] The nanoemulsion composition provided by the present invention comprises 30wt% to 88wt% of oil, 10wt% to 45wt% of emulsifier, 1wt% to 10wt% of silymarin and 1wt% to 20wt% of retinoids, wherein the emulsifier is selected from polysorbate and polyoxyethylene hydrogenated castor oil, and the LogP value of the oil is less than or equal to 5.

[0026] In the above-mentioned nanoemulsion composition, on the one hand, the synergistic emulsification effect of polysorbate and polyoxyethylene hydrogenated castor oil, as well as the coating effect of the oil, significantly improves the solubility and stability of silymarin and retinol, and achieves the absence of the addition of co-emulsifiers such as alcohol or polyols in the nanoemulsion composition system, thereby reducing skin irritation; on the other hand, retinoids can act as co-emulsifiers to further enhance the solubility of silymarin, while silymarin helps to inhibit the oxidation of retinoids, further improving the stability of retinoids.

[0027] Therefore, the nanoemulsion composition of the present invention effectively improves the solubility and stability of silymarin and retinoids. When added to water, it can self-emulsify to form a stable nanoemulsion system, thereby increasing the content, utilization rate and skin permeability of silymarin in cosmetics, achieving effects such as anti-oxidation, moisturizing and anti-wrinkle, and delaying skin aging. At the same time, it does not contain alcohol or polyols or other emulsifiers, so it is less irritating to the skin and more beneficial to skin health, especially suitable for sensitive skin.

[0028] In one embodiment, the mass ratio of the polysorbate ester to the polyoxyethylene hydrogenated castor oil is 1:1 to 4:3, thereby effectively ensuring emulsification and achieving the addition of emulsifiers such as alcohol or polyols in the nanoemulsion composition. This improves the solubility and stability of silymarin and retinoids, and avoids phenomena such as water layering or precipitation when the nanoemulsion composition is added to water.

[0029] In one embodiment, the polysorbate is selected from at least one of polysorbate-20, polysorbate-80, or polysorbate-60.

[0030] Preferably, the polysorbate is selected from at least one of polysorbate-20 or polysorbate-80.

[0031] Understandably, the polysorbate can be polysorbate-20 alone, polysorbate-80 alone, or a mixture of polysorbate-20 and polysorbate-80, and the present invention does not limit the mass fraction of polysorbate-20 and polysorbate-80 in the mixture.

[0032] In one embodiment, the polyoxyethylene hydrogenated castor oil is selected from at least one of PEG-40 hydrogenated castor oil or PEG-60 hydrogenated castor oil.

[0033] In one embodiment, the retinoid is selected from at least one of retinol, retinol derivatives, or psoralen.

[0034] It should be noted that the retinol derivatives include, but are not limited to, retinaldehyde, retinyl esters, retinoic acid, etc., such as hydroxypinazone retinoate, retinyl propionate, retinyl palmitate, retinyl retinoate, tocopheryl retinoate, etc.

[0035] In one embodiment, the oil is selected from at least one of lauroyl sarcosine isopropyl ester or propylene glycol octanoate, which is beneficial to further improve the coating effect of the oil on silymarin and retinoids, thereby improving the solubility and stability of silymarin and retinoids. At the same time, the oil has a low LogP value, high polarity and hydrophilicity, which can improve the solubility of the nanoemulsion composition.

[0036] In one embodiment, when the oil comprises lauroyl sarcosine isopropyl ester and propylene glycol octanoate, the mass ratio of lauroyl sarcosine isopropyl ester to propylene glycol octanoate is greater than 1:1.

[0037] In one embodiment, the oil content in the nanoemulsion composition is preferably 40% to 60% by mass.

[0038] In one embodiment, the mass fraction of the emulsifier in the nanoemulsion composition is preferably 15% to 40%, which is beneficial to further improve the solubility and stability of silymarin and retinoids, thereby further reducing the risk of problems such as aqueous layering or precipitation when the nanoemulsion composition is added to water.

[0039] It should be noted that, within the above range, the higher the mass fraction of the emulsifier, the smaller the particle size of the formed nanoemulsion, resulting in better skin permeability. This is beneficial for further improving the utilization rate of active substances such as silymarin and retinoids, while ensuring that the nanoemulsion has less irritation to the skin.

[0040] Retinoids, as fat-soluble compounds, have good skin permeability and can stimulate fibroblasts to synthesize collagen, increasing skin elasticity. Their main effects include anti-aging, repairing the skin barrier, evening skin tone, and controlling oil and acne. However, due to their highly reactive chemical properties, retinoids are sensitive to light and heat and are easily oxidized into non-bioactive substances. Furthermore, prolonged storage, high temperatures, and preservatives can also affect the stability of retinoid products. This invention utilizes the synergistic effect of silymarin and retinoids, effectively inhibiting retinoid oxidation and improving its stability.

[0041] To further improve the antioxidant capacity and stability of retinoids, and at the same time to further improve the solubility of silymarin, the mass ratio of silymarin to retinoids is preferably 1:0.1 to 1:10, more preferably 1:0.5 to 1:8.

[0042] The present invention also provides a method for preparing the nanoemulsion composition as described above, comprising the following steps:

[0043] The oil, emulsifier, and silymarin are mixed to obtain a mixed solution;

[0044] The nanoemulsion composition is obtained by dissolving retinoids in the mixed solution.

[0045] It is understood that the silymarin raw material is a solid powder. In the step of mixing oil, emulsifier and silymarin, when the mixed solution is clear and transparent, it indicates that the silymarin has been completely dissolved.

[0046] The preparation method of the above-mentioned nanoemulsion composition is simple, and the raw materials do not contain emulsifiers such as alcohol or polyols, which makes it less irritating to the skin and more beneficial to skin health, especially suitable for sensitive skin.

[0047] In one embodiment, the temperature is 75°C to 95°C during the step of mixing the oil, emulsifier, and silymarin.

[0048] In one embodiment, the temperature is 50°C to 60°C during the step of dissolving retinoids in the mixed solution.

[0049] It should be noted that stirring or shaking can be performed to promote the dissolution of silymarin and retinoids, but this invention does not limit the scope of the invention.

[0050] Specifically, the oil, emulsifier, and silymarin are stirred at a speed of 500 rpm to 1000 rpm for 30 to 60 minutes to promote complete dissolution of silymarin.

[0051] Specifically, after completely dissolving the retinoids by stirring at a speed of 500 r / min to 1000 r / min for 3 min to 5 min, the nanoemulsion composition is obtained by continuing stirring and cooling to room temperature.

[0052] The present invention also provides the application of the nanoemulsion composition as described above in cosmetics.

[0053] It should be noted that the nanoemulsion composition of the present invention is a transparent, clear, and homogeneous liquid. It can be subsequently added to an aqueous phase and other organic solvents to produce nanoemulsions for use in cosmetics. During use, it releases silymarin and retinoids to exert the efficacy of the active substances. The nanoemulsion composition of the present invention is generally applicable to different types of cosmetic systems and can be used in skin care products such as face creams, serums, or lotions. It can also be used in color cosmetic products. It is understood that when the nanoemulsion composition is used in different types of cosmetic systems, the cosmetic system may also include other excipients, which the present invention does not limit.

[0054] Specifically, when the above-mentioned nanoemulsion composition is added to water, an oil-in-water nanoemulsion can be spontaneously formed under normal temperature conditions by slight shaking or stirring. The nanoemulsion has a particle size of about 30nm to 150nm, has excellent skin permeability, and is less irritating to the skin. This increases the amount and utilization rate of silymarin in cosmetics, and achieves effects such as anti-oxidation, moisturizing and anti-wrinkle, and delaying skin aging.

[0055] In one embodiment, the nanoemulsion composition of the present invention can self-emulsify in water to form a stable nanoemulsion system, so that the mass fraction of silymarin in the nanoemulsion system can reach 0.5% to 6%, and then cosmetics with a specific silymarin content can be formulated according to needs.

[0056] The following specific examples will further illustrate the nanoemulsion composition, its preparation method, and its application.

[0057] This invention provides a general and / or specific description of the materials and test methods used in all embodiments and comparative examples. Unless otherwise specified, all reagents or instruments used in all embodiments and comparative examples are commercially available reagents or instruments.

[0058] Example 1

[0059] According to the proportions provided in Table 1, the oil, emulsifier, and silymarin were stirred at 85°C and 1000 r / min for 60 min to obtain a clear and transparent liquid.

[0060] The above clear and transparent liquid was cooled to 60°C, and retinol was added according to the ratio provided in Table 1. The mixture was stirred at 800 r / min for 5 min to completely dissolve the retinol. Stirring and cooling continued until the temperature reached 25°C, at which point stirring was stopped to obtain the nanoemulsion composition.

[0061] Example 2

[0062] According to the proportions provided in Table 1, the oil, emulsifier, and silymarin were stirred at 75°C and 800 r / min for 60 min to obtain a clear and transparent liquid.

[0063] The above clear and transparent liquid was cooled to 50°C, and retinol was added according to the ratio provided in Table 1. The mixture was stirred at 1000 r / min for 3 min to completely dissolve the retinol. Stirring and cooling continued until the temperature reached 25°C, at which point stirring was stopped to obtain the nanoemulsion composition.

[0064] Examples 3 to 15 were prepared according to the preparation method of Example 1. In Examples 3 to 15, the types and mass ratios of oils, emulsifiers, silymarin and retinol were added according to Table 1.

[0065] Table 1

[0066]

[0067] Comparative Example

[0068] All comparative examples were prepared according to the preparation method of Example 1, wherein the types and mass ratios of each component were added according to Table 2.

[0069] Table 2

[0070]

[0071] The nanoemulsion compositions prepared in the examples and comparative examples were subjected to performance tests. The test indicators and test methods are shown below:

[0072] (1) Stability of silymarin: The nanoemulsion compositions prepared in Examples 1 to 19 and Comparative Examples 1 to 10 were diluted in water to a concentration of 5% and placed at constant temperatures of 4°C, 20°C, 45°C and 50°C for 1 week. The stability test was carried out at 45°C under constant temperature and light conditions.

[0073] (2) Stability of retinoids: The nanoemulsion compositions prepared in Examples 1 to 19 and Comparative Examples 1 to 10 were placed under constant temperature and light conditions at 45°C for 1 month, and the changes in retinoid content before and after placement were tested by high performance liquid chromatography.

[0074] (3) Nanoemulsion particle size: The nanoemulsion compositions prepared in Examples 1 to 19 and Comparative Examples 1 to 10 were diluted in water to a concentration of 1% aqueous solution, and then analyzed using Anton Paar Litesizer. TM The particle size of nanoemulsions in aqueous solution was characterized using a 500 nm laser particle scattering instrument.

[0075] (4) Skin irritation: Cream A and Cream B were prepared according to the proportions in Table 3. Cream A used the nanoemulsion composition prepared in Example 1, with a mass fraction of silymarin of 0.06% and a mass fraction of retinol of 0.10%. Cream B did not contain the above nanoemulsion composition. Thirty-five volunteers aged 18 to 60 years were selected. Irritation tests were conducted according to the "Cosmetic Safety Technical Specifications 2015 Edition" - Human Skin Patch Test. Cream A and Cream B were added to the patch tester. The patch tester containing the cream was then applied to the back of the subject with non-irritating adhesive tape. The patch tester was gently pressed with the palm of the hand to make it evenly applied to the skin. After 24 hours, the patch tester was removed. The residue of the test substance on the test site was gently wiped away with a moistened cotton ball. After 0.5 hours, the skin reaction was observed after the indentation disappeared. If the result was negative, the patch tester was observed again 24 hours after the patch was removed.

[0076] Table 3

[0077]

[0078]

[0079] The performance test results of the above embodiments and comparative examples are shown in Tables 4 to 6, respectively.

[0080] Table 4

[0081]

[0082]

[0083] Note: No stability tests were performed on the nanoemulsion compositions that were not dissolved in water.

[0084] Table 5

[0085]

[0086]

[0087] Table 6

[0088]

[0089] Note: 1 *(26) This indicates that the number of people experiencing adverse reactions is 1, corresponding to subject number 26.

[0090] As can be seen from the test results in Tables 4 to 6, under the same test conditions, the nanoemulsion composition prepared in the examples showed better solubility of silymarin compared to the nanoemulsion composition prepared in the comparative examples, with no precipitation or stratification. Furthermore, the retinoid content showed minimal change after one month of constant temperature and light exposure at 45°C. Additionally, the nanoemulsion composition prepared in the examples could form an oil-in-water nanoemulsion with a particle size of 77 nm to 149 nm when added to water. Moreover, when the nanoemulsion composition prepared in Example 1 was used as a face cream, with the use of the oils and emulsifiers of this invention, and with a silymarin mass fraction of 0.06% and a retinoid mass fraction of 0.10%, it showed no adverse reactions on human skin and minimal skin irritation.

[0091] Therefore, the nanoemulsion composition provided by this invention can effectively improve the solubility of silymarin, without precipitation or stratification when added to water. It also enhances the light and heat resistance stability of retinoids, and self-emulsifies in water to form a stable nanoemulsion system. This increases the content, utilization rate, and skin permeability of silymarin in cosmetics, achieving antioxidant, moisturizing, anti-wrinkle, and anti-aging effects. Furthermore, it does not contain alcohol or polyols or other emulsifiers, resulting in less skin irritation and promoting skin health, especially suitable for sensitive skin. In addition, the nanoemulsion composition has a simple preparation process, is easy to use, and is widely applicable to different types of cosmetic systems, showing broad application prospects.

[0092] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0093] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention. Therefore, the protection scope of this invention patent should be determined by the appended claims.

Claims

1. A nanoemulsion composition, characterized in that, The nanoemulsion composition comprises 30wt%~88wt% of oil, 10wt%~45wt% of emulsifier, 1wt%~10wt% of silymarin, and 1wt%~20wt% of retinoids. The emulsifier is polysorbate and polyoxyethylene hydrogenated castor oil. The retinoids are selected from at least one of retinol, hydroxypinazone retinate, retinyl propionate, and psoralen. The oil has a LogP value less than or equal to 5. The oil is lauroyl sarcosine isopropyl ester or lauroyl sarcosine isopropyl ester and propylene glycol octanoate. When the oil is lauroyl sarcosine isopropyl ester and propylene glycol octanoate, the mass ratio of lauroyl sarcosine isopropyl ester to propylene glycol octanoate is greater than 1:

1.

2. The nanoemulsion composition according to claim 1, characterized in that, The mass ratio of the polysorbate to the polyoxyethylene hydrogenated castor oil is 1:1 to 4:

3.

3. The nanoemulsion composition according to claim 1, characterized in that, The polysorbate is selected from at least one of polysorbate-20, polysorbate-60 or polysorbate-80; And / or, the polyoxyethylene hydrogenated castor oil is selected from at least one of PEG-40 hydrogenated castor oil or PEG-60 hydrogenated castor oil.

4. The nanoemulsion composition according to claim 1, characterized in that, In the nanoemulsion composition, the oil has a mass fraction of 40% to 60%. And / or, in the nanoemulsion composition, the mass fraction of the emulsifier is 15% to 40%; And / or, the mass ratio of silymarin to retinoid is 1:0.1 to 1:

10.

5. A method for preparing the nanoemulsion composition according to any one of claims 1 to 4, characterized in that, Includes the following steps: The oil, emulsifier, and silymarin are mixed to obtain a mixed solution; The nanoemulsion composition is obtained by dissolving retinoids in the mixed solution.

6. The method for preparing the nanoemulsion composition according to claim 5, characterized in that, During the step of mixing the oil, emulsifier, and silymarin, the temperature is 75℃~95℃; And / or, in the step of dissolving retinoids in the mixed solution, the temperature is 50°C to 60°C.

7. The use of a nanoemulsion composition as described in any one of claims 1 to 4 in the preparation of cosmetics.

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