Permeation enhancing composition, application and cosmetic

Abstract

The invention belongs to the field of daily chemicals, and discloses a penetration enhancing composition which comprises betaine and isosorbide dimethyl ether, the weight ratio of the betaine to the isosorbide dimethyl ether is (20-30): (15-25). The composition is more excellent in permeation enhancing effect, and the combined permeation enhancing mechanism of the composition is that the isosorbide dimethyl ether can temporarily open lipids between adjacent cells by influencing lipids of a stable structure between keratinocytes, and meanwhile, a hydrophilic part in the structure can conveniently help permeation of water-soluble effective components, so that the combined permeation enhancing effect of the composition is improved. Therefore, the absorption effect of the skin is improved. The betaine effectively increases the skin hydration degree, and when the skin water content is increased, membrane pores are enlarged, the tissue tightness is reduced, and the permeation and absorption of active ingredients are increased. Meanwhile, the invention further discloses application of the composition and cosmetics.

Description

Technical Field

[0001] The invention relates to the field of daily chemicals, in particular to a penetration-promoting composition, use and cosmetics. Background Art

[0002] Isosorbide dimethyl ether can dissolve free fat in the skin, thereby penetrating the skin membrane and promoting the penetration of active ingredients into the epidermis, giving full play to the effectiveness of active ingredients. A large number of local epidermal and oral medication and toxicology studies have shown that isosorbide dimethyl ether is non-irritating, non-toxic and very safe.

[0003] It has been demonstrated in prior art studies that dimethyl isosorbide not only increases the solubility of various active ingredients in the skin, but also reduces the driving force for penetration in the formulation. Dimethyl isosorbide can enhance the ability of dermal delivery without enhancing transdermal delivery.

[0004] Reports on related patent technologies for isosorbide dimethyl ether can be found in the following patent documents:

[0005] Publication No. CN115414265A, the subject is a composition, a cream and a preparation method thereof with color correction, skin rejuvenation and moisturizing effects, and discloses that the composition includes a penetration enhancer, and the penetration enhancer includes any one of laurocapram, dimethyl isosorbide or N-alkylbenzisothiazolone or a combination of at least two thereof.

[0006] Publication No. CN118526491A, the subject is a water-soluble transparent composition and a preparation method thereof, which discloses that the composition contains a penetration enhancer, dimethyl isosorbide.

[0007] In addition, dimethyl isosorbide can also be used as a dissolution-promoting solvent.

[0008] In the prior art, no one has yet mentioned a solution for further improving the penetration-enhancing effect of dimethyl isosorbide. Summary of the invention

[0009] The object of the present invention is to provide a penetration-promoting composition, which has a more excellent penetration-promoting effect.

[0010] At the same time, the invention also discloses the application and cosmetics of the composition.

[0011] To achieve the above object, the present invention provides the following technical solutions:

[0012] A penetration-enhancing composition comprises betaine and isosorbide dimethyl ether; the weight ratio of the betaine to isosorbide dimethyl ether is 20-30:15-25.

[0013] In this field, the ways that affect skin penetration are roughly as follows:

[0014] In terms of channels, it is divided into stratum corneum cell pathway, hair follicle, sebaceous gland and sweat gland and other accessory organ pathways, and stratum corneum cell interstitial pathway;

[0015] In terms of mechanism, it is divided into transdermal absorption pathway and transdermal penetration pathway;

[0016] In the present invention, the interstitial space pathway of the stratum corneum and the transdermal absorption pathway are utilized;

[0017] As is well known, dimethyl isosorbide can dissolve free fat in the skin, thereby penetrating the skin membrane, promoting the penetration of active ingredients into the epidermis, and giving full play to the effectiveness of the active ingredients. It can be considered as a penetration enhancer based on the stratum corneum cell pathway.

[0018] In the present invention, betaine and dimethyl isosorbide can synergistically promote penetration, and the mechanism is that dimethyl isosorbide can temporarily open the lipids between adjacent cells by affecting the lipids that stabilize the structure between keratinocytes, and at the same time, the hydrophilic part of the structure can help the penetration of water-soluble active ingredients, thereby improving the absorption effect of the skin. Betaine effectively increases the hydration of the skin. When the water content of the skin increases, the membrane pores increase, the tissue tightness decreases, and the penetration and absorption of the active ingredients increase.

[0019] Therefore, based on the above theoretical analysis, we believe that the present invention utilizes the synergistic combination of betaine and dimethyl isosorbide to achieve the purpose of penetration enhancement based on the intercellular pathway of the stratum corneum.

[0020] The above penetration-enhancing composition further comprises inositol or thiotaurine.

[0021] Further studies have shown that inositol can slightly enhance the penetration-enhancing ability of betaine to dimethyl isosorbide, and thiotaurine can significantly enhance the penetration-enhancing ability of betaine to dimethyl isosorbide.

[0022] The reason is that tight junctions have been shown to be the main determinant of paracellular permeability.

[0023] Inositol is involved in various reactions in the human body, mediating cell signal transduction, helping to regulate the structure and function of tight junctions (TJs), maintaining cell osmotic pressure, and thus helping to restore the epidermal barrier.

[0024] Thiotaurine affects the absorption and transport of other molecules by cells by increasing the fluidity of cell membranes or by interacting with specific proteins on cell membranes.

[0025] In some preferred embodiments of the present invention, the weight ratio of inositol to dimethyl isosorbide is 0.2-1:15-25.

[0026] In some preferred embodiments of the present invention, the weight ratio of thiotaurine to isosorbide dimethyl ether is 0.2-1:15-25.

[0027] In some preferred embodiments of the present invention, water is also contained, and the total amount of the betaine and dimethyl isosorbide is equivalent to 35-55wt% of the total amount of the penetration enhancing composition.

[0028] In some preferred embodiments of the present invention, a diol is further included, and the polyol is 1,2-pentanediol and / or 1,2-hexanediol.

[0029] At the same time, the present invention also discloses the use of any of the above penetration-enhancing compositions in preparing cosmetics.

[0030] Finally, the present invention also discloses a cosmetic comprising any one of the penetration-enhancing compositions described above.

[0031] Compared with the prior art, the present invention has the following beneficial effects:

[0032] The present invention adopts betaine in combination with dimethyl isosorbide, which can significantly improve the penetration-promoting effect of dimethyl isosorbide. The reason is that dimethyl isosorbide can temporarily open the lipids between adjacent cells by affecting the lipids with stable structures between keratinocytes, and the hydrophilic part of the structure can help the penetration of water-soluble active ingredients, thereby improving the absorption effect of the skin. Betaine effectively increases the hydration of the skin. When the water content of the skin increases, the membrane pores increase, the tissue tightness decreases, and the penetration absorption of the active ingredients increases. DETAILED DESCRIPTION

[0033] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0034] The present invention simulates the transdermal effect of the composition based on computer simulation and actual detection methods, using SIS TM The transdermal software predicted the transdermal effect of the formula containing bosine in 10, and the Franz diffusion cell permeability experiment of VC ethyl ether in the sample was carried out using the back skin of suckling pigs. The effect and mechanism of the present invention were demonstrated through computer simulation and actual experiments.

[0035] Part I Computer simulation of the permeation enhancement effect of betaine and dimethyl isosorbide

[0036] This part uses bisphenol A as the research object to explore the effects of betaine and dimethyl isosorbide alone and in combination on the content of bisphenol A in the stratum corneum, active epidermis and dermis (using SIS TM transdermal software).

[0037] The test formula is shown in Table 1 below;

[0038] Table 1 Formula Unit: g

[0039]

[0040] Example 9

[0041] The same as Example 4, except that the formula further contains 0.5 g of inositol.

[0042] Example 10

[0043] The same as Example 4, except that the formula further contains 0.5 g of thiotaurine.

[0044] Blank Group

[0045] The blank group was pure water, with 2g / 100g of phosphodiester added.

[0046] The test results are shown in Table 2 below;

[0047] During the simulation, the physogenin content in the stratum corneum tended to be constant after 5 h, and its approximate concentration was 180 μg / cm 2 , therefore, the horny layer bosera content is not used as a performance indicator of the present invention;

[0048] In the active epidermis and dermis, the content of Bose-like protein increases with time. In the simulation process of 1 to 24 hours, the content of Bose-like protein is the highest at 24 hours, so the cumulative content of Bose-like protein in the active epidermis and dermis at 24 hours is displayed respectively.

[0049] Table 2 Permeation results Unit: μg / cm 2

[0050] Active epidermis Dermis Example 1 46 407 Example 2 51 522 Example 3 53 562 Example 4 57 587 Example 5 50 513 Example 6 45 465 Example 7 33 360 Example 8 12 112 Example 9 58 598 Example 10 65 659 Blank group 4 52

[0051] After simulation testing, two conclusions can be drawn:

[0052] 1. The penetration-enhancing effect of betaine is very weak, while that of dimethyl isosorbide is relatively strong. When betaine and dimethyl isosorbide are used in combination, especially when the amount of dimethyl isosorbide is relatively large, it has a more excellent penetration-enhancing effect.

[0053] 2. Inositol and thiotaurine have penetration-enhancing effects, among which thiotaurine has a more obvious synergistic effect. This shows that enhancing the fluidity of cell membranes or the activity of skin transport-related proteins has a more obvious effect on the penetration-enhancing effect of the formula.

[0054] Through the above experiments, it can be preliminarily confirmed that betaine and dimethyl isosorbide have synergistic effects, and thiotaurine has a more obvious effect on the penetration enhancement of the formula. Later, actual verification was carried out through the back skin of suckling pigs.

[0055] Part II Franz diffusion cell permeability test of VC ethyl ether in the sample on the back skin of suckling pigs

[0056] 2.1 Experimental methods

[0057] Test model and test system

[0058] In this test, the back skin of a one-month-old suckling pig was selected as the test model, and the suckling pig skin-Franz cell was selected as the test system.

[0059] Reagents

[0060] PBS buffer solution (Solabol).

[0061] equipment

[0062] Intelligent transdermal diffusion instrument (Guangzhou Huaqiao), Franz cell (Guangzhou Huaqiao), TU-1900 double beam UV-visible spectrophotometer, KQ3200E ultrasonic cleaner (Kunshan Shumei), low temperature high speed centrifuge (Hunan Xiangyi)

[0063] Sample Information

[0064] See Table 4 below;

[0065] Test equipment

[0066] The structure of the TK-12D transdermal diffusion tester includes a constant temperature water bath, a control box, an operating table, 12 transdermal diffusion cells, a rehydration tube and a connecting tube. A rehydration port control box is provided on the upper part of the inner bottle of the transdermal diffusion cell, which is connected to the constant temperature water bath and the operating table through electric wires. The constant temperature water bath is connected to the outer bottle of the transdermal diffusion cell through a connecting tube, and the rehydration bottle is connected to the rehydration port of the transdermal diffusion cell through a connecting tube. The transdermal diffusion cell is placed on the operating table. This device can carry out multiple transdermal experiments at the same time without interfering with each other and without bubbles. The volume of its receiving chamber is 8.5mL and the diffusion area is 3.14cm. The diffusion cell is composed of two cylindrical glass tubes, and the patch sandwiched between them divides the upper and lower chambers into two chambers. The upper chamber is the diffusion chamber, and the lower chamber is the receiving chamber. A sampling tube is connected to the right part of the receiving chamber for sampling, sampling and venting bubbles.

[0067] Test steps

[0068] Preparation of ex vivo suckling pig skin

[0069] The back skin of one-month-old suckling piglets stored at -20°C was thawed with deionized water at room temperature and repeatedly rinsed with PBS buffer.

[0070] Transdermal absorption capacity determination

[0071] 1) First, fix the pig skin between the supply chamber and the receiving chamber of the Franz cell diffusion tank, with the stratum corneum layer of the pig skin facing the supply chamber and the dermis layer facing the receiving chamber;

[0072] 2) Add 7.0 mL of receiving solution into the receiving chamber, tighten and fix the pig skin, then add 1.5 mL of receiving solution (PBS) into the receiving chamber through a sampler, exhaust the air, and make the dermis layer of the skin in close contact with the receiving solution;

[0073] 3) Sample loading: Add the sample to the skin surface in the supply chamber. The effective penetration area S is about 3.14 cm 2 . Add the sample to the surface of the pig skin and spread the sample evenly from the center of the skin to the edge. Each sample was repeated 3 times in parallel (three replicates were made from skin from specific parts of independent donors);

[0074] 4) Infiltration: Turn on the electromagnetic stirrer and stir at a speed of 300 rpm, maintain a constant temperature water bath at (32±1)°C, and ensure that there are no bubbles in the water bath interlayer;

[0075] 5) Collect skin samples at 1h, 4h, 9h, 19h, and 24h. Use a sampler to extract 2.0mL of receiving solution through the sampling tube, and then place it in a 2mL EP tube. In addition, add an equal amount of receiving solution after each sampling.

[0076] Transdermal content test

[0077] After 24 hours of penetration, the contents of the samples on the skin, in the skin, and under the skin at each time point in different experimental groups were detected by UV spectrophotometer. The specific processing method is as follows:

[0078] 1) Test of the unpenetrated part of the skin: After 24 hours, use a 1 mL pipette to take up PBS and repeatedly blow and wash the skin surface, wash 5 times for a total of 5 mL, and place it in a 5 mL EP tube for testing;

[0079] 2) Test of the skin: Use a sterile scalpel to cut the skin along the inner edge of the supply chamber, cut the skin into pieces, add 5 mL PBS and ultrasonically extract for 60 minutes. After the ultrasonication is completed, aspirate the supernatant and wait for testing;

[0080] 3) Subcutaneous part test: At each time point, 2.0 mL of receiving solution drawn from the receiving chamber was placed in a 2LEP tube for testing.

[0081] 5. UV spectrophotometer detection

[0082] The test conditions can be seen in Table 3;

[0083] Table 3 VC ethyl ether detection conditions

[0084] UV spectrophotometer detection parameters Test substances VC ethyl ether Detection wavelength 246nm Sample cell thickness 1cm Scan speed 1nm / s

[0085] Cumulative penetration calculation method:

[0086] Q=CnxV+ZCixV0(i=1...n-1)

[0087] Where: Q: cumulative penetration

[0088] V: Volume of receiving liquid in the receiving chamber

[0089] V0: The volume of each sample

[0090] Ci: Drug concentration in the receiving area from the first sampling to the last sampling

[0091] Cn: Sample concentration measured at the nth sampling point.

[0092] The sample formula can be seen in Table 4; the blank sample is the VCE brightening stock solution produced by our company; the test sample is the VCE brightening stock solution added with the penetration-enhancing composition; in the test sample, the VCE brightening stock solution contains 6 wt % of the penetration-enhancing composition.

[0093] The formula of the penetration-enhancing composition can be seen in Table 4;

[0094] Table 4 Recipe

[0095]

[0096]

[0097] The test results refer to Table 5;

[0098] Table 5 Test results Unit: Cumulative permeation amount Q (μg)

[0099]

[0100]

[0101] Result analysis:

[0102] 1. The test results of samples 1 to 3, 5, 8 and blank samples are consistent with the computer simulation results. Unlike the expected result, the penetration-enhancing effect of sample 2 is different from that of sample 1 and the computer simulation results. From the computer simulation results, the penetration-enhancing effect of betaine is very poor. From the reagent experiment, it shows a certain penetration-enhancing effect, and its penetration-enhancing effect is better than that of inositol in this experiment (without considering the specific concentration);

[0103] From samples 1 to 3, it can be seen that the penetration-enhancing effect of dimethyl isosorbide alone is significantly better than that of betaine; and from the combination of the two, the combined effect is even better.

[0104] 2. According to the test results of samples 4 to 6 and samples 7 to 9, inositol can effectively promote penetration at a dosage of 0.5wt%, but increasing the dosage to 1wt% will have a negative effect; and thiotaurine can show a more obvious and excellent synergistic effect at a dosage of more than 0.5wt%.

[0105] 3. It can be seen from samples 10 and 11 that neither thiotaurine nor inositol has a significant penetration-enhancing effect when used alone, and the penetration-enhancing effect of inositol is better than that of thiotaurine.

[0106] Based on the above results, we can draw the following conclusions: The use of betaine in combination with dimethyl isosorbide can significantly improve the penetration-enhancing effect of dimethyl isosorbide. The reason is that dimethyl isosorbide opens the lipids between keratinocytes, and betaine increases skin hydration, enlarges membrane pores, and improves the penetration effect.

[0107] Thiotaurine further enhances the penetration-enhancing effect by increasing the fluidity of cell membranes or by interacting with specific proteins on the cell membrane, thereby affecting the cell's absorption and transport of other molecules.

[0108] The raw materials used in the present invention are all non-irritating raw materials. After a rabbit eye irritation test, the formula of the present invention is non-irritating after being diluted 20 times, and can be used in most cosmetic formulas.

Claims

1. A penetration-enhancing composition, characterized in that The invention comprises betaine and isosorbide dimethyl ether; the weight ratio of the betaine to isosorbide dimethyl ether is 20-30:15-25.

2. The penetration-enhancing composition according to claim 1, characterized in that Also included are inositol or thiotaurine.

3. The penetration-promoting composition according to claim 2, characterized in that The weight ratio of the inositol to the isosorbide dimethyl ether is 0.2-1:15-25.

4. The penetration-promoting composition according to claim 2, characterized in that The weight ratio of the thiotaurine to isosorbide dimethyl ether is 0.2-1:15-25.

5. The penetration-enhancing composition according to any one of claims 1 to 4, characterized in that: The composition also contains water, and the total amount of the betaine and dimethyl isosorbide is equivalent to 35-55wt% of the total amount of the penetration-enhancing composition.

6. The penetration-enhancing composition according to any one of claims 1 to 4, characterized in that: Also included are diols, wherein the polyols are 1,2-pentanediol and / or 1,2-hexanediol.

7. Use of the penetration-enhancing composition according to any one of claims 1 to 6 in preparing cosmetics.

8. A cosmetic, characterized in that: Contains the penetration-enhancing composition according to any one of claims 1 to 6.

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