Composition for promoting transdermal absorption of collagen and use thereof

Abstract

The application provides a composition for promoting transdermal absorption of collagen and application thereof. The composition comprises collagen, squalane, and hyaluronic acid or a salt thereof, wherein the molecular weight of the hyaluronic acid or the salt thereof is 400 kDa-2200 kDa. The composition of the application can form a closed moisturizing film on the skin surface by using hyaluronic acid or a salt thereof with a specific molecular weight and squalane, promote the hydration of the skin, and accelerate the transdermal absorption of collagen in the composition.

Description

Technical Field

[0001] This application belongs to the field of cosmetic technology, specifically relating to a composition for promoting transdermal collagen absorption and its application, and the application of squalane and hyaluronic acid or their salts in promoting transdermal collagen absorption. Background Technology

[0002] Natural collagen is a biological macromolecule that is widely present in animal bodies and has a variety of biological functions and pharmacological effects.

[0003] For example, natural collagen plays a role in repairing and regenerating tissues. It can promote wound healing, support cell proliferation and tissue regeneration, and provide structural support, and is widely used in tissue repair and regeneration after trauma and surgery. Bone collagen is one of the main components of bone tissue, providing support and elasticity, and enhancing bone structure. In the field of skin care, natural collagen plays a role in moisturizing, elasticity, and firming the skin, and is widely used in anti-aging and skin care products to promote skin firmness and smoothness. Collagen can also serve as a carrier for drug delivery systems. Through modification and functionalization, drugs can be stably encapsulated in collagen to achieve sustained and targeted drug release, improve drug efficacy, and reduce dosage and side effects. In terms of immune regulation, collagen can alter immune responses and regulate the function of immune cells, thus having a potential therapeutic effect on immune-related diseases such as autoimmune diseases and inflammatory diseases.

[0004] Given the aforementioned effects of natural collagen, its role in the pharmaceutical field is extensive and important. However, natural collagen typically has a large molecular weight, resulting in poor transdermal absorption, which limits its application in certain scenarios. Summary of the Invention

[0005] In view of the problems existing in the prior art, this application provides a composition containing collagen, and the use of squalane and hyaluronic acid or their salts in promoting transdermal absorption of collagen.

[0006] Specifically, this application relates to the following aspects:

[0007] 1. A composition for promoting transdermal absorption of collagen, comprising collagen, squalane, and hyaluronic acid or a salt thereof, wherein the molecular weight of the hyaluronic acid or the salt thereof is 400 kDa to 2200 kDa.

[0008] 2. The composition according to claim 1, wherein the hyaluronic acid or its salt has a molecular weight of 400kDa-1500kDa.

[0009] 3. The composition according to claim 1 or 2, wherein the mass ratio of said collagen, squalane, and said hyaluronic acid or a salt thereof is (0.1-5):(2-5):(0.05-0.2).

[0010] 4. The composition according to any one of items 1-3, wherein the composition further comprises an emulsifier, preferably selected from one or more of polysorbate-20, sodium acrylate copolymer / lecithin, cetearyl alcohol / cetearyl glucoside, cetearyl alcohol and glyceryl stearate / PEG-100 stearate.

[0011] 5. The composition according to any one of items 1-4, wherein the collagen is animal-derived collagen, preferably collagen extracted from bovine Achilles tendon tissue.

[0012] 6. Use of the composition of any one of items 1-5 in promoting transdermal absorption of collagen.

[0013] 7. Application of squalane and hyaluronic acid or their salts in promoting transdermal collagen absorption.

[0014] 8. The application according to item 7, wherein the molecular weight of the hyaluronic acid or its salt is 400kDa-2200kDa, preferably 400kDa-1500kDa.

[0015] 9. The application according to item 7 or 8, wherein the mass ratio of said collagen, squalane, and said hyaluronic acid salt or salt thereof is (0.1-5):(2-5):(0.05-0.2).

[0016] 10. The application according to any one of items 7-9, wherein the collagen is animal-derived collagen, preferably collagen extracted from bovine Achilles tendon tissue.

[0017] The composition of this application, by using hyaluronic acid or its salt of a specific molecular weight, and squalane, can accelerate the transdermal absorption of collagen in the composition, especially the transdermal absorption of animal-derived collagen. Detailed Implementation

[0018] The present application is further illustrated below with reference to embodiments. It should be understood that the embodiments are only used to further illustrate and explain the present application and are not intended to limit the present application.

[0019] Unless otherwise defined, technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art. While similar or identical methods and materials may be applied in experimental or practical applications, materials and methods are described herein. In case of conflict, the definitions included herein shall prevail. Furthermore, materials, methods, and examples are for illustrative purposes only and are not intended to be limiting. The present application is further described below with reference to specific embodiments, but is not intended to limit the scope of the application.

[0020] This application provides a composition for promoting transdermal absorption of collagen, comprising collagen, squalane, and hyaluronic acid or a salt thereof. The hyaluronic acid or its salts have a molecular weight of 400kDa-2200kDa, for example, 400kDa, 410kDa, 420kDa, 430kDa, 440kDa, 450kDa, 460kDa, 470kDa, 480kDa, 490kDa, 500kDa, 550kDa, 600kDa, 650kDa, 700kDa, 750kDa, 800kDa, 850kDa, 900kDa, 950kDa, 1000kDa, 1100kDa, 1200kDa, 1300kDa, 1400kDa, 1500kDa, 1600kDa, 1700kDa, 1800kDa, 1900kDa, 2000kDa, 2100kDa, 2200kDa, and any range between these values.

[0021] Those skilled in the art will understand that the molecular weight of hyaluronic acid or its salts as used herein refers to the average molecular weight of hyaluronic acid or its salts in the composition. In some specific embodiments, the molecular weight of the hyaluronic acid or its salts is 400 kDa to 1500 kDa.

[0022] In some specific embodiments, the molecular weight of the hyaluronic acid or its salt is 400kDa-1000kDa.

[0023] In some specific embodiments, the collagen is animal-derived collagen. Animal-derived collagen can encompass various animal-derived collagens known in the art, such as collagen extracted from animal skin, cartilage, fascia, or ligament tissue.

[0024] In some specific embodiments, the collagen is collagen extracted from bovine Achilles tendon tissue.

[0025] In some specific embodiments, the collagen extracted from the bovine Achilles tendon tissue is obtained by using bovine Achilles tendon tissue as raw material, employing low-temperature extraction technology, and removing the antigenic ends of animal collagen by enzymatic digestion under acidic conditions.

[0026] In some specific embodiments, the molecular weight of the collagen is 100k to 350kDa.

[0027] In some specific embodiments, the mass ratio of the collagen, squalane, and hyaluronic acid or its salt is (0.1-5):(2-5):(0.05-0.2). For (0.1-5):(2-5):(0.05-0.2), 0.1-5 can be 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5, and any range between these values; 2-5 can be 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5, and any range between these values; 0.05-0.2 can be 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, 0.19, 0.2, and any range between these values.

[0028] In some specific embodiments, the composition for promoting transdermal absorption of collagen includes collagen, squalane, and hyaluronic acid or a salt thereof, wherein the molecular weight of the hyaluronic acid or salt thereof is 400kDa-2200kDa, and the mass ratio of the collagen, squalane, and the hyaluronic acid or salt thereof is (0.1-5):(2-5):(0.05-0.2).

[0029] In some specific embodiments, the composition for promoting transdermal absorption of collagen includes collagen, squalane, and hyaluronic acid or a salt thereof, wherein the molecular weight of the hyaluronic acid or salt thereof is 400kDa-1000kDa, and the mass ratio of the collagen, squalane, and the hyaluronic acid or salt thereof is (0.1-5):(2-5):(0.05-0.2).

[0030] In some specific embodiments, the composition contains 0.1-5% collagen, 2-5% squalane, and 0.05-0.2% hyaluronic acid or its salt.

[0031] Furthermore, the composition for promoting transdermal collagen absorption may also include an emulsifier.

[0032] In some specific embodiments, the emulsifier is selected from one or more of polysorbate-20, sodium acrylate copolymer / lecithin, cetearyl alcohol / cetearyl glucoside, cetearyl alcohol and glyceryl stearate / PEG-100 stearate.

[0033] In some specific embodiments, the composition for promoting transdermal absorption of collagen includes collagen, squalane, hyaluronic acid or a salt thereof, and an emulsifier, wherein the molecular weight of the hyaluronic acid or salt thereof is 400kDa-2200kDa, the mass ratio of the collagen, squalane, and the hyaluronic acid or salt thereof is (0.1-5):(2-5):(0.05-0.2), and the emulsifier is selected from one or more of polysorbate-20, sodium acrylate copolymer / lecithin, cetearyl alcohol / cetearyl glucoside, cetearyl alcohol and glyceryl stearate / PEG-100 stearate.

[0034] In some specific embodiments, the composition for promoting transdermal absorption of collagen includes collagen, squalane, hyaluronic acid or its salt, and an emulsifier, wherein the molecular weight of the hyaluronic acid or its salt is 400kDa-1500kDa, and the mass ratio of the collagen, squalane, hyaluronic acid or its salt, and the emulsifier is (0.1-5):(2-5):(0.05-0.2):(0.2-3), wherein the emulsifier is selected from one or more of polysorbate-20, sodium acrylate copolymer / lecithin, cetearyl alcohol / cetearyl glucoside, cetearyl alcohol, and glyceryl stearate / PEG-100 stearate.

[0035] In some specific embodiments, the composition for promoting transdermal absorption of collagen includes collagen, squalane, hyaluronic acid or a salt thereof, and an emulsifier, wherein the molecular weight of the hyaluronic acid or salt thereof is 400kDa-1500kDa, the mass ratio of the collagen, squalane, and the hyaluronic acid or salt thereof is (0.1-5):(2-5):(0.05-0.2), and the emulsifier is selected from one or more of polysorbate-20, sodium acrylate copolymer / lecithin, cetearyl alcohol / cetearyl glucoside, cetearyl alcohol and glyceryl stearate / PEG-100 stearate.

[0036] In some specific embodiments, the composition for promoting transdermal absorption of collagen includes collagen, squalane, hyaluronic acid or its salt, and an emulsifier, wherein the molecular weight of the hyaluronic acid or its salt is 400kDa-1500kDa, and the mass ratio of the collagen, squalane, hyaluronic acid or its salt, and the emulsifier is (0.1-5):(2-5):(0.05-0.2):(0.2-3), wherein the emulsifier is selected from one or more of polysorbate-20, sodium acrylate copolymer / lecithin, cetearyl alcohol / cetearyl glucoside, cetearyl alcohol, and glyceryl stearate / PEG-100 stearate.

[0037] In some specific embodiments, the composition for promoting transdermal collagen absorption comprises collagen, squalane, hyaluronic acid or its salt, an emulsifier, and water, wherein the molecular weight of the hyaluronic acid or its salt is 400kDa-2200kDa, the mass ratio of the collagen, squalane, and the hyaluronic acid or its salt is (0.1-5):(2-5):(0.05-0.2), and the emulsifier is selected from one or more of polysorbate-20, sodium acrylate copolymer / lecithin, cetearyl alcohol / cetearyl glucoside, cetearyl alcohol, and glyceryl stearate / PEG-100 stearate.

[0038] In some specific embodiments, the composition for promoting transdermal collagen absorption comprises collagen, squalane, hyaluronic acid or its salt, an emulsifier, and water, wherein the molecular weight of the hyaluronic acid or its salt is 400kDa-1500kDa, the mass ratio of the collagen, squalane, and the hyaluronic acid or its salt is (0.1-5):(2-5):(0.05-0.2), and the emulsifier is selected from one or more of polysorbate-20, sodium acrylate copolymer / lecithin, cetearyl alcohol / cetearyl glucoside, cetearyl alcohol, and glyceryl stearate / PEG-100 stearate.

[0039] In some specific embodiments, the composition contains 0.1-5% collagen, 2-5% squalane, 0.05-0.2% hyaluronic acid or its salt, and 0.2-3% emulsifier.

[0040] This application also provides a method for preparing any of the above compositions, comprising the following steps:

[0041] (1) Mix squalane and emulsifier, heat to dissolve, and obtain phase A;

[0042] (2) Dissolve hyaluronic acid or its salt in water to obtain phase B;

[0043] (3) Dissolve collagen in water to obtain phase C;

[0044] (4) Mix phase A and phase B, homogenize them, add phase C and stir until homogeneous to obtain the composition.

[0045] This application also provides the use of any of the above compositions in promoting transdermal absorption of collagen.

[0046] This application also provides the use of squalane and hyaluronic acid or their salts in promoting transdermal absorption of collagen.

[0047] In the above applications, the molecular weight of the hyaluronic acid or its salt, the collagen, the squalane, and the mass of the hyaluronic acid salt or its salt are as described above for compositions that promote transdermal collagen absorption.

[0048] The composition of this application, by using hyaluronic acid or its salt with a molecular weight of 400kDa-2200kDa in combination with squalane, can form a closed moisturizing film on the skin surface, promote skin hydration, and accelerate the transdermal absorption of collagen in the composition.

[0049] Example

[0050] The animal-derived collagen used in the following examples and comparative examples is collagen extracted from bovine Achilles tendon tissue (purchased from Beijing Yierkang Biotechnology Co., Ltd.).

[0051] Example 1

[0052] Preparation of compositions that promote transdermal collagen absorption

[0053] Step a): Accurately weigh 2g of squalane and 1g of glyceryl stearate / PEG-100 stearate into a beaker, heat to 80-85℃, and obtain phase A;

[0054] Step b): Accurately weigh 0.2g of sodium hyaluronate (molecular weight 500kDa), add 50ml of purified water at 90℃, stir well to obtain phase B;

[0055] Step c): Accurately weigh 2g of animal-derived collagen and add it to 40ml of purified water to dissolve, thus obtaining phase C;

[0056] Step d): Mix phase A and phase B, homogenize at 7000 rpm to 8000 rpm for 5 min to 10 min; cool to 45°C, add phase C and the remaining water to a total mass of 100 g, stir slowly until homogeneous to obtain the composition.

[0057] Examples 2-5

[0058] The difference between Examples 2-5 and Example 1 lies in the amount of squalane, sodium hyaluronate, or collagen added. In Example 2, the amount of squalane is 5g and the amount of sodium hyaluronate is 0.05g. In Example 3, the amount of squalane is 4g and the amount of sodium hyaluronate is 0.1g. In Example 4, the amount of squalane is 4g, the amount of sodium hyaluronate is 0.1g, and the amount of collagen is 0.1g. In Example 5, the amount of squalane is 4g, the amount of sodium hyaluronate is 0.1g, and the amount of collagen is 5g.

[0059] Examples 6-8

[0060] The only difference between Examples 6-8 and Example 3 is the molecular weight of the sodium hyaluronate. In Example 6, the molecular weight of the sodium hyaluronate is 1000 kDa, in Example 7 it is 1200 kDa, and in Example 8 it is 2000 kDa.

[0061] Example 9

[0062] The difference between Example 9 and Example 3 lies in the type of emulsifier. In Example 9, the emulsifier is cetearyl alcohol / cetearyl glucoside.

[0063] Example 10

[0064] The difference between Example 10 and Example 3 is the amount of emulsifier added. In Example 10, the amount of emulsifier added was 0.25g.

[0065] Comparative Example 1

[0066] The difference between Comparative Example 1 and Example 3 is that squalane and sodium hyaluronate are not added.

[0067] Preparation of compositions that promote transdermal collagen absorption

[0068] Step a): Accurately weigh 1g of glyceryl stearate / PEG-100 stearate into a beaker, heat to 80-85℃, and obtain phase A;

[0069] Step b): 50 ml of purified water at 90℃ is phase B;

[0070] Step c): Accurately weigh 2g of animal-derived collagen and add it to 40ml of purified water to dissolve, thus obtaining phase C;

[0071] Step d): Mix phase A and phase B, homogenize at 7000 rpm to 8000 rpm for 5 min to 10 min; cool to 45°C, add phase C and the remaining water to a total mass of 100 g, stir slowly until homogeneous to obtain the composition.

[0072] Comparative Examples 2-3

[0073] The only difference between Comparative Examples 2-3 and Comparative Example 1 is the amount of collagen added. In Comparative Example 2, the amount of collagen added was 0.1g, while in Example 3, the amount of collagen added was 5g.

[0074] Comparative Example 4

[0075] The only difference between Comparative Example 4 and Example 3 is that squalane is not added.

[0076] Preparation of compositions that promote transdermal collagen absorption

[0077] Step a): Accurately weigh 1g of glyceryl stearate / PEG-100 stearate into a beaker, heat to 80-85℃, and obtain phase A;

[0078] Step b): Accurately weigh 0.1g of sodium hyaluronate (molecular weight 500kDa), add 50ml of purified water at 90℃, stir well to obtain phase B;

[0079] Step c): Accurately weigh 2g of animal-derived collagen and add it to 40ml of purified water to dissolve, thus obtaining phase C;

[0080] Step d): Mix phase A and phase B, homogenize at 7000 rpm to 8000 rpm for 5 min to 10 min; cool to 45°C, add phase C and the remaining water to a total mass of 100 g, stir slowly until homogeneous to obtain the composition.

[0081] Comparative Example 5

[0082] The only difference between Comparative Example 5 and Example 3 is that sodium hyaluronate is not added.

[0083] Preparation of compositions that promote transdermal collagen absorption

[0084] Step a): Accurately weigh 4g of squalane and 1g of glyceryl stearate / PEG-100 stearate into a beaker, heat to 80-85℃, and obtain phase A;

[0085] Step b): 50 ml of purified water at 90℃ is phase B;

[0086] Step c): Accurately weigh 2g of animal-derived collagen and add it to 40ml of purified water to dissolve, thus obtaining phase C;

[0087] Step d): Mix phase A and phase B, homogenize at 7000 rpm to 8000 rpm for 5 min to 10 min; cool to 45°C, add phase C and the remaining water to a total mass of 100 g, stir slowly until homogeneous to obtain the composition.

[0088] Comparative Example 6

[0089] The difference between Comparative Example 6 and Example 3 lies in the amount of squalane and sodium hyaluronate added. In Comparative Example 6, the amount of squalane added was 0.2g, and the amount of sodium hyaluronate added was 2g.

[0090] Comparative Example 7

[0091] Step a): Accurately weigh 2g of squalane and 1g of glyceryl stearate / PEG-100 stearate into a beaker, heat to 80-85℃, and obtain phase A;

[0092] Step b): Accurately weigh 0.2g of sodium hyaluronate (molecular weight 230kDa), add 50ml of purified water at 90℃, stir well to obtain phase B;

[0093] Step c): Accurately weigh 2g of animal-derived collagen and add it to 40ml of purified water to dissolve, thus obtaining phase C;

[0094] Step d): Mix phase A and phase B, homogenize at 7000 rpm to 8000 rpm for 5 min to 10 min; cool to 45°C, add phase C and the remaining water to a total mass of 100 g, stir slowly until homogeneous to obtain the composition.

[0095] Please refer to Table 1 for the dosage of each component in the above embodiments and comparative examples.

[0096] Table 1. Amounts of components used in the examples and comparative examples.

[0097]

[0098]

[0099] Experimental Example: Determination of Collagen Transdermal Absorption Rate

[0100] To study the transdermal absorption behavior of intact collagen, the transdermal absorption rate of collagen was determined using the conventional method FITC fluorescein isothiocyanate.

[0101] Mice that had already acclimatized to the laboratory environment were dehaired and prepared one day in advance. Before the experiment, the prepared skin area was cleaned with shower gel or facial cleanser, and then rinsed three times with sodium carbonate-sodium bicarbonate buffer (pH=9). The prepared skin area was 2cm × 2cm. 1g of the composition from each of the above examples and comparative examples was applied to the same prepared skin area using a medical cotton swab. 30 minutes after application, five mice from each group were cleaned of the prepared skin area with sodium carbonate-sodium bicarbonate buffer (pH=9). The cleansing solution was collected and stored for later use. A spectrophotometer was used to quantitatively analyze the collagen in the cleansing solution, identifying collagen that failed to penetrate the skin.

[0102] The transdermal penetration rate is calculated using the following formula:

[0103]

[0104] The transdermal absorption rates for each embodiment and comparative example are summarized in Table 2.

[0105] Table 2. Transdermal absorption rate (%) of collagen in the composition

[0106]

[0107]

[0108] As can be seen from Table 2,

[0109] Comparative Examples 1 and Examples 1-3, 6-10, Comparative Examples 2 and 4, and Comparative Examples 3 and 5 show that collagen alone has a low transdermal absorption rate, but when combined with squalane and hyaluronic acid, the transdermal absorption rate can be improved.

[0110] As can be seen from Comparative Examples 1, 4, 5 and Example 3, hyaluronic acid and squalane each have the effect of improving the transdermal absorption rate of collagen. However, their improvement effect is still significantly different from that of Example 3. Therefore, the combination of hyaluronic acid and squalane has a synergistic effect on the transdermal absorption of collagen.

Claims

1. A composition for promoting transdermal absorption of collagen, comprising collagen, squalane, and hyaluronic acid or a salt thereof, wherein the molecular weight of the hyaluronic acid or salt thereof is 400 kDa-2200 kDa, and the mass ratio of the collagen, squalane, and the hyaluronic acid or salt thereof is (0.1-5):(2-5):(0.05-0.2).

2. The composition according to claim 1, wherein the hyaluronic acid or its salt has a molecular weight of 400 kDa-1500 kDa.

3. The composition according to claim 1, wherein the composition further comprises an emulsifier.

4. The composition according to claim 3, wherein the emulsifier is selected from one or more of polysorbate-20, sodium acrylate copolymer / lecithin, cetearyl alcohol / cetearyl glucoside, cetearyl alcohol and glyceryl stearate / PEG-100 stearate.

5. The composition according to any one of claims 1-4, wherein the collagen is animal-derived collagen.

6. The composition according to claim 5, wherein the collagen is collagen extracted from bovine Achilles tendon tissue.

7. Use of the composition of any one of claims 1-6 in the preparation of articles that promote transdermal absorption of collagen.

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