Biological whitening composition containing milk exosome as well as preparation method and application of biological whitening composition

Abstract

The invention discloses a biological whitening composition containing milk exosome as well as a preparation method and application of the biological whitening composition. According to the milk exosome composition, multiple compounded emulsion emulsifiers are adopted, the vesicle structure of the milk exosome can be protected, the milk exosome can stably exist in the composition, and therefore the whitening effect is stably achieved. In addition, by adding the glabridin and the daisy flower extract and cooperating with the milk exosome, a stronger whitening effect is achieved, the glabridin has the effects of inhibiting melanin and resisting inflammation and accurately plays a whitening role, and the daisy flower extract can achieve the whitening effect from the source by reducing melanin generation. The whitening effects of the whitening compositions jointly play a role in inhibiting melanogenesis genes, reducing melanogenesis and preventing melanin transfer and transfer, and the whitening effects are played from various ways.

Description

Technical Field

[0001] The present invention belongs to the technical field of skin care products, and in particular relates to a biological whitening composition containing milk exosomes, and a preparation method and application thereof. Background Art

[0002] Currently, the whitening products on the market mainly rely on chemical whitening agents, such as niacinamide, arbutin, tranexamic acid, etc. Although these ingredients have certain whitening effects, their application has significant defects: Niacinamide: The purification process is complicated. If the purity is insufficient, impurities such as niacin may remain, causing adverse reactions such as skin flushing and stinging. When used in high concentrations (>5%), about 30% of people with sensitive skin will experience intolerance (such as redness, swelling, and itching).

[0003] Arbutin: It is easily decomposed into hydroquinone under light or high temperature, which has potential cytotoxicity. Long-term use may cause depigmentation or skin sensitivity.

[0004] Tranexamic acid: Although it can inhibit the production of melanin, it may interfere with coagulation function and there is controversy over its safety.

[0005] In addition, chemical whitening agents have a single mechanism of action, mainly inhibiting tyrosinase activity or blocking melanin transport, making it difficult to achieve multi-dimensional synergistic whitening and unable to meet consumers' dual demands for "high efficiency + gentleness".

[0006] Milk exosomes are a bioactive ingredient that has attracted much attention in recent years. In addition to whitening, milk exosomes also have the potential to resist oxidation and promote cell repair.

[0007] However, there are two major technical bottlenecks in the application of milk exosomes: Poor stability: The vesicle structure is easily destroyed by temperature, pH and mechanical shear force, resulting in leakage of contents. In vitro experiments showed that the activity of exosomes in conventional emulsions decreased by 40% after 7 days of storage.

[0008] Low formula compatibility: Traditional emulsification systems cannot effectively encapsulate exosomes, causing them to interact with other ingredients in the formula (such as preservatives and surfactants), accelerating their inactivation.

[0009] CN117180156A: discloses a milk exosome emulsion containing resveratrol, but the resveratrol is loaded by a co-culture method, which has a complicated process and does not solve the problem of the stability of the exosomes themselves.

[0010] CN118845493A: focuses on anti-aging effects, only identifies exosomes by morphology, and does not propose a solution for application stability.

[0011] In summary, the existing technologies have not been able to effectively balance the stability and whitening efficacy of milk exosomes, and there is an urgent need for an innovative formulation strategy. Summary of the Invention

[0012] In view of the problems existing in the prior art, the present invention proposes a method for solving the poor stability and low compatibility of milk exosomes in applications, and expands the application of milk exosomes in skin care products.

[0013] In the first aspect, the present invention provides a biological whitening composition containing milk exosomes, The composition comprises the following components in parts by weight: Humectant 9 - 12 parts; Emollient 15 - 25 parts; Thickener 0.1 - 0.3 part; Multiple emulsion emulsifier 4 - 6 parts; pH regulator 0.02 - 0.15 part; Whitening active ingredient 15 - 23 parts; The balance is water, and the sum of the parts by weight of the above components is 100 parts.

[0014] Further, the multiple emulsion emulsifier comprises the following components in parts by weight: Polyglycerol-3 polyricinoleate 2 - 3 parts; Glycerol oleate citrate 0.4 - 1.8 parts; Polyglycerol-3 diisostearate 0.4 - 1.8 parts; Cetearyl alcohol 0.5 - 1 part.

[0015] Further, the whitening active ingredient comprises the following components in parts by weight: Milk exosomes 5 - 10 parts; Glabridin 3 - 5 parts; Chamomile flower extract 5 - 10 parts.

[0016] Further, the humectant is at least one of glycerol, 1,2-pentanediol, 1,2-hexanediol, 1,3-propanediol, allantoin, and betaine.

[0017] Further, the emollient is at least one of dimethicone, squalane, caprylic / capric triglyceride, and shea butter.

[0018] In the second aspect, the present invention provides a preparation method of the above biological whitening composition containing milk exosomes, comprising the following steps: (a) Preparing an aqueous phase: Mixing the humectant, thickener and water, and heating to 70 - 85°C for dissolution; (b) Preparation of the oil phase: Mix the emollient with the multiple emulsifier and heat to 80 - 87 °C until melted. (c) Homogeneous emulsification: Add the oil phase to the aqueous phase, homogenize and stir, then cool down to 40 - 45 °C. (d) Add the whitening active ingredient, adjust the pH to 6.0 - 6.5, and stir to mix.

[0019] Further, the homogenization conditions in step (c) are 82 - 85 °C, 45 - 55 Hz, and 8 - 12 min.

[0020] Thirdly, the present invention provides an application of the above - mentioned biological whitening composition containing milk exosomes in the preparation of whitening skin care products.

[0021] 1) The present invention adopts a compound multiple - emulsion structure. The multiple emulsion has a unique multi - compartment structure of "three - phase and two - film". In this structure, oil droplets containing water droplets are suspended in the aqueous phase to form an emulsion. This multiple - emulsion system can embed milk exosomes in it, protect the vesicle structure of milk exosomes, enable milk exosomes to stably exist in the composition, and thus stably exert the whitening effect.

[0022] 2) The present invention adds glabridin and daisy flower extract, and cooperates with milk exosomes to achieve a stronger whitening effect. Glabridin has the effects of inhibiting melanin and anti - inflammation, and precisely exerts the whitening effect. The daisy flower extract can play a whitening effect from the source by reducing melanin production. The whitening effects of these whitening compositions work together at the level of inhibiting melanin - generating genes, reducing melanin production, and preventing the transport and transfer of melanin. They exert the whitening effect through multiple pathways, which is not a simple superposition of effects, but a more scientific and effective whitening method. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] The present invention will be further described below with reference to the accompanying drawings.

[0024] Figure 1 This is a picture taken by a transmission electron microscope of the biological whitening composition containing milk exosomes prepared in Example 1 of the present invention. The vesicle structure of regular and uniform milk exosomes can be observed.

[0025] Figure 2 This is a picture taken by a transmission electron microscope of the biological whitening composition containing milk exosomes prepared in Example 3 of the present invention. The vesicle structure of regular and uniform milk exosomes can be observed.

[0026] Figure 3 This is a picture taken by a transmission electron microscope of the composition prepared in Comparative Example 1. It can be observed that the vesicle structure of milk exosomes is damaged, irregular and incomplete, and the content has leaked out.

[0027] Figure 4For the melanin change rate graph for verifying the human body whitening effect in the verification experiment, after 4 weeks of testing, it can be seen that the melanin content in the Example 1 group is significantly lower than that in the Comparative Example 2 group.

[0028] Figure 5 For the heme change rate graph for verifying the human body whitening effect in the verification experiment, after 4 weeks of testing, it can be seen that the heme content in the Example 1 group is extremely significantly lower than that in the Comparative Example 2 group.

[0029] Figure 6 For the skin brightness change rate graph for verifying the human body whitening effect in the verification experiment, after 4 weeks of testing, it can be seen that the skin brightness in the Example 1 group is significantly higher than that in the Comparative Example 2 group.

[0030] Figure 7 The picture taken by an optical microscope of the biological whitening composition containing milk exosomes prepared in Example 1 of the present invention shows a multi-compartment structure of "three phases and two membranes" that can be observed.

[0031] Figure 8 The picture taken by an optical microscope of the biological whitening composition containing milk exosomes prepared in Example 3 of the present invention shows a multi-compartment structure of "three phases and two membranes" that can be observed.

[0032] Figure 9 The picture taken by an optical microscope of the composition prepared in Comparative Example 1 shows an oil droplet structure and no special "three phases and two membranes" structure. Detailed implementation mode

[0033] To better understand the present invention, the present invention will be described in detail and explained below through the description of the preferred specific embodiments of the present invention, but the present invention is not limited in any form.

[0034] The raw materials or chemical reagents used in the embodiments of the present invention are all obtained through conventional commercial channels unless otherwise specified.

[0035] Sources of some raw materials: Polyglyceryl-3 polyricinoleate, glyceryl oleate citrate, polyglyceryl-3 diisostearate, specification: 1 kg, manufacturer: Oriane Industry (Shanghai) Co., Ltd.; Milk exosomes: Raw material trade name: Polybiome® milk phospholipid vesicle extract, specification: 1 kg, manufacturer: Shaanxi Microbiome Biotechnology Co., Ltd.; Daisy extract: Raw material trade name: Polybiome® daisy extract PF-A, specification: 1 kg, manufacturer: Shaanxi Microbiome Biotechnology Co., Ltd.; Glabridin: Raw material trade name: Nefytin® glabridin, specification: 1 kg, manufacturer: Shaanxi Baihong Synthetic Biology Technology Co., Ltd.; Examples

[0036] This embodiment provides a method for preparing a biological whitening composition containing milk exosomes: First, weigh the raw materials of each component: 1) Aqueous phase raw materials: 11.5 g of a humectant, including: 4 g of glycerol, 2 g of 1,2-pentanediol, 1.2 g of 1,2-hexanediol, 3 g of 1,3-propanediol, 0.3 g of allantoin, and 1 g of betaine; Thickener: 0.15 g of acrylate / C10-30 alkyl acrylate cross-linked polymer; 2) Oil phase raw materials: 20 g of an emollient, including: 5 g of dimethyl silicone, 5 g of squalane, 5 g of caprylic / capric triglyceride, and 5 g of shea butter; 5 g of a multiple emulsion emulsifier, including: 2 g of polyglyceryl-3 polyricinoleate, 1 g of glyceryl oleate citrate, 1 g of polyglyceryl-3 diisostearate, and 1 g of cetearyl alcohol; 3) Whitening active ingredients: Including 8 g of milk exosomes, 5 g of glabridin, and 5 g of daisy extract; Preparation method: Step 1: Weigh and dissolve the aqueous phase. Weigh the aqueous phase raw materials first and add them to the reaction vessel. Heat to 85°C and stir until dissolved and transparent. Keep warm for 30 minutes for standby; Step 2: Weigh and dissolve the oil phase. Weigh the oil phase raw materials first and add them to the reaction vessel. Start stirring and adjust the rotation speed until the liquid surface shakes up and down. At the same time, heat the dosing tank to 85°C and stir until all the oils and fats are dissolved; Step 3: Homogenize and emulsify. Pump the oil phase obtained in Step 2 into the main aqueous phase pot, keep the temperature at 83 - 87°C, stir while pumping, and adjust the rotation speed until the liquid surface shakes up and down. After pumping, keep the temperature at 82 - 85°C, start homogenizing and stirring, and homogenize for 10 minutes under the condition of 50 Hz.

[0037] Step 4: After the homogenization in Step 3 is completed, start cooling with circulating water. When the temperature drops to 54 - 60°C, add sodium hydroxide to adjust the pH of the material to 6.5, stir evenly. When the temperature drops to 40 - 45°C, add the whitening combination agent containing milk exosomes, adjust the rotation speed until the liquid surface shakes up and down, and stir for 30 minutes to obtain the biological whitening composition containing milk exosomes. Example

[0038] This embodiment provides a method for preparing a biological whitening composition containing milk exosomes: First, weigh the raw materials of each component: 1) Aqueous phase raw materials: 9 g of humectant, including: 3 g of glycerin, 1.5 g of 1,2 - pentanediol, 1.2 g of 1,2 - hexanediol, 2 g of 1,3 - propanediol, 0.3 g of allantoin, 1 g of betaine; 0.15 g of thickener, including: 0.15 g of acrylate / C10 - 30 alkyl acrylate cross - polymer; 2) Oil - phase raw materials: 16 g of emollient, including: 4 g of dimethicone, 4 g of squalane, 4 g of caprylic / capric triglyceride, 4 g of shea butter; 4 g of multiple - emulsion emulsifier, including: 2 g of polyglyceryl - 3 polyricinoleate, 0.7 g of glyceryl oleate citrate, 0.7 g of polyglyceryl - 3 diisostearate, 0.6 g of cetearyl alcohol; 3) Whitening active ingredients: Including 5 g of milk exosomes, 3 g of glabridin, 5 g of daisy flower extract; Preparation method: Step 1: Weigh and dissolve the water - phase. Weigh the water - phase raw materials first and add them to the reaction vessel, heat up to 85 °C and stir until dissolved and transparent, keep warm for 30 minutes for standby; Step 2: Weigh and dissolve the oil - phase. Weigh the oil - phase raw materials first and add them to the reaction vessel, start stirring, adjust the rotation speed until the liquid surface shakes up and down, at the same time heat up the dosing tank to 85 - 87 °C and stir until all the oils and fats are dissolved; Step 3: Homogenize and emulsify. Pump the oil - phase obtained in Step 2 into the main water - phase pot, keep the temperature at 83 - 87 °C, pump while stirring, adjust the rotation speed until the liquid surface shakes up and down. After pumping, keep the temperature at 82 - 85 °C, start the homogenizing stirring, and homogenize for 10 minutes under the condition of 50 Hz.

[0039] Step 4: After the homogenization in Step 3 is completed, start the circulating water to cool down, when the temperature drops to 54 - 60 °C, add sodium hydroxide, adjust the pH of the material to 6.5, stir evenly, when the temperature drops to 40 - 45 °C, add the whitening combination agent containing milk exosomes, adjust the rotation speed until the liquid surface shakes up and down, and stir for 30 minutes to obtain the biological whitening composition containing milk exosomes. Example

[0040] This example provides a preparation method of a biological whitening composition containing milk exosomes: First, weigh the raw materials of each component: 1) Water - phase raw materials: 12 g of humectant, including: 4 g of glycerin, 2.5 g of 1,2 - pentanediol, 1.2 g of 1,2 - hexanediol, 3 g of 1,3 - propanediol, 0.3 g of allantoin, 1 g of betaine; 0.15 g of thickener, including: 0.15 g of acrylate / C10-30 alkyl acrylate cross-linked polymer; 2) Oil phase raw materials: 24 g of emollient, including: 6 g of dimethicone, 6 g of squalane, 6 g of caprylic / capric triglyceride, 6 g of shea butter; 6 g of multiple emulsion emulsifier, including: 2 g of polyglyceryl-3 polyricinoleate, 1.5 g of glyceryl oleate citrate, 1.5 g of polyglyceryl-3 diisostearate, 1 g of cetearyl alcohol; 3) Whitening active ingredients: Including 10 g of milk exosomes, 3 g of glabridin, 10 g of daisy flower extract; Preparation method: Step 1: Weigh and dissolve the aqueous phase. Weigh the aqueous phase raw materials first and add them to the reaction vessel. Heat to 85 °C and stir until dissolved and transparent. Keep warm for 30 minutes for standby; Step 2: Weigh and dissolve the oil phase. Weigh the oil phase raw materials first and add them to the reaction vessel. Start stirring and adjust the rotation speed until the liquid surface shakes up and down. At the same time, heat the dispensing tank to 85-87 °C and stir until all the oils and fats are dissolved; Step 3: Homogenize and emulsify. Pump the oil phase obtained in Step 2 into the main aqueous phase pot, keep the temperature at 83-87 °C, stir while pumping, and adjust the rotation speed until the liquid surface shakes up and down. After pumping, keep the temperature at 82-85 °C, start the homogenizing stirring, and homogenize for 10 minutes under the condition of 50 Hz.

[0041] Step 4: After the homogenization in Step 3 is completed, start the circulating water to cool down. When the temperature drops to 54-60 °C, add sodium hydroxide and adjust the pH of the material to 6.5. Stir evenly. When the temperature drops to 40-45 °C, add the whitening combination agent containing milk exosomes, adjust the rotation speed until the liquid surface shakes up and down, and stir for 30 minutes to obtain the biological whitening composition containing milk exosomes.

[0042] The difference between this comparative example and Example 1 is that the multiple emulsion emulsifier is replaced with 4 g of a conventional emulsifier, including: 2 g of dioctyldodecyl lauroyl glutamate and 2 g of stearyl alcohol, and the rest is the same as in Example 1.

[0043] The difference between this comparative example and Example 1 is that the whitening active ingredients are not added, and the rest is the same as in Example 1.

[0044] Efficacy verification: 1. Verification of the vesicle structure stability in the composition: Use a transmission electron microscope to take pictures of the compositions prepared in Example 1, Example 3, and Comparative Example 1 using negative staining technology. Example 1 ( Figure 1 ) and Example 3 ( Figure 2) An emulsifier capable of forming multiple emulsion results is used. Under negative staining technology photography, a large number of regular and uniform bilayer membrane vesicle structures with a particle size of 100 - 200 nm can be observed, which are the vesicle structures of normal state milk exosomes. In Comparative Example 1 ( Figure 3 ) Only a common emulsifier is added. Under transmission electron microscopy photography, the vesicle structure is damaged, irregular and incomplete, and the content flows out.

[0045] 2. Verification of human skin whitening effect: In order to verify the whitening effect of the biological whitening composition containing milk exosomes, 28 healthy volunteers were selected. The inner side of the arm was used as the test site. The test substances were divided into two groups. One group was the sample of Example 1, and the other group was the sample of Comparative Example 2. They were applied in the specified area. After 4 weeks of application, three indexes of melanin, heme and skin glossiness on the skin surface of the test site were measured. According to the experimental data and result analysis, the whitening effect of an invented biological whitening composition containing milk exosomes was verified.

[0046] The initial values (melanin, heme, skin glossiness) of the test site were tested using a Glossymeter GL200 and a Mexameter MX18 probe respectively, with 3 technical replicates for each area. The corresponding samples were applied to the positions of the matrix area and the composition area respectively, 2 times a day, and the amount of each sample application was 0.1 g until completely absorbed. After 4 weeks, the testers detected the melanin, heme and skin glossiness of each area respectively.

[0047] The results showed that after 4 weeks of testing, the melanin content in the application part of the volunteers in the Example 1 group was significantly reduced ( Figure 5 ), the heme content was extremely significantly reduced ( Figure 6 ), and the skin brightness was significantly increased ( Figure 7 ), indicating that the whitening composition containing milk exosomes prepared in the Example 1 group had an obvious soothing effect and had significant advantages in aspects such as whitening and brightening the skin color.

[0048] 3. Identification of multiple emulsion structure: The compositions prepared in Example 1, Example 3 and Comparative Example 1 were photographed with an optical microscope. In Example 1 ( Figure 7 ) and Example 3 ( Figure 8 ), it can be seen that the multiple emulsion has a unique multi-compartment structure of "three-phase two-membrane". In Comparative Example 1 ( Figure 9 ), only oil droplet structures can be observed, without a special "three-phase two-membrane" structure.

[0049] Although the preferred embodiments of the present invention have been described, those skilled in the art can make additional changes and modifications to these embodiments once they know the basic creative concepts.

[0050] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalent technologies, the present invention is also intended to include these modifications and variations.

Claims

1. A biological whitening composition containing milk exosomes, characterized in that: The composition comprises the following components in parts by weight: Moisturizer 9~12 parts; Emollient 15~25 parts; Thickener 0.1~0.3 parts; Multiple emulsion emulsifier 4-6 parts; pH regulator 0.02~0.15 parts; 15~23 parts of whitening active ingredients; The balance is water, and the sum of the weight parts of the above components is 100 parts.

2. The composition according to claim 1, characterized in that The multiple emulsion emulsifier comprises the following components in parts by weight: 2-3 parts of polyglyceryl-3 polyricinoleate; Glyceryl oleate citrate 0.4-1.8 parts; 0.4-1.8 parts of polyglyceryl-3 diisostearate; 0.5~1 part of cetearyl alcohol.

3. The composition according to claim 1, characterized in that The whitening active ingredient comprises the following components in parts by weight: 5-10 portions of milk exosomes; 3-5 parts of glabridin; 5-10 parts of daisy flower extract.

4. The composition according to claim 1, characterized in that The moisturizing agent is at least one of glycerin, 1,2-pentanediol, 1,2-hexanediol, 1,3-propylene glycol, allantoin and betaine.

5. The composition according to claim 1, characterized in that The emollient is at least one of dimethyl siloxane, squalane, caprylic / capric triglyceride, and avocado butter.

6. A method for preparing a biological whitening composition containing milk exosomes as claimed in any one of claims 1 to 5, comprising the following steps: (a) Prepare the aqueous phase: mix the humectant, thickener and water and heat to 70-85°C to dissolve; (b) preparing the oil phase: mixing the emollient and the multiple emulsifier and heating to 80-87°C to dissolve; (c) Homogenization and emulsification: add the oil phase into the water phase, stir homogenously and cool to 40-45°C; (d) Add whitening active ingredients, adjust the pH to 6.0-6.5, and stir to mix.

7. The preparation method according to claim 6, characterized in that: The homogenization conditions of step (c) are 82-85° C., 45-55 Hz, and 8-12 min.

8. Use of the biological whitening composition containing milk exosomes as claimed in any one of claims 1 to 5 in the preparation of whitening skin care products.

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