Permeation enhancing composition containing bis-diethoxydiethylene glycol cyclohexane 1, 4-dicarboxylate and rose oil and application thereof

Abstract

The invention provides a permeation enhancing composition containing bis-diethoxy diethylene glycol cyclohexane 1, 4-dicarboxylate and rose oil and application of the permeation enhancing composition. The permeation enhancing composition comprises bis-diethoxy diethylene glycol cyclohexane 1, 4-dicarboxylate and rose oil. According to the rose oil and the preparation method thereof disclosed by the invention, through the combination of the bis-diethoxy diethylene glycol cyclohexane 1, 4-dicarboxylate and the rose oil, the permeation enhancing effect is improved.

Description

Technical Field

[0001] The present application relates to the field of cosmetic technology, and in particular to the field of penetration enhancement technology. Background Art

[0002] Percutaneous absorption refers to the ability of the skin to absorb external substances. The skin is not an absolutely tight, seamless, and impermeable barrier, and it has a certain degree of permeability and absorption. The effective ingredients in percutaneous products enter the epidermis or dermis through percutaneous absorption, and accumulate and exert their effects in this area. The penetration and absorption of the skin mainly occur through three pathways: the stratum corneum, the hair follicles, the sebaceous glands, and the sweat duct openings. The main absorption pathway is to penetrate into the stratum corneum cells, and then reach the dermis through other layers of the epidermis and be absorbed.

[0003] However, since the stratum corneum of the skin is a naturally hydrophobic structure, oil-soluble ingredients are more easily penetrated and absorbed, while water-soluble ingredients are difficult to be absorbed, which makes it difficult for water-soluble functional ingredients to work effectively.

[0004] Bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate is a water-oil amphiphilic oil. It can be used not only as a moisturizer and emollient, but also as a penetration enhancer to promote the transdermal absorption of water-soluble ingredients. For example, bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate can greatly improve the absorption of tranexamic acid, thereby greatly improving the whitening effect. In addition to tranexamic acid, the transdermal absorption effects of other water-soluble ingredients have also been greatly improved. For example, the penetration of VC derivatives increased by about 2 times after 3 hours of application. For example, it can increase the penetration rate of bosine by about 60 times. Bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate not only has a good penetration-enhancing effect in skin care products, but also has a good effect in hair care products. It allows water-soluble ingredients such as hydrolyzed keratin to better penetrate the hair scales into the hair cortex, play a better hair care role, and repair the strength and elasticity of the hair. In addition, in cleaning products, bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate can also enhance the cleaning effect. Summary of the invention

[0005] The present application unexpectedly found in practical application that the rose oil without penetration-promoting effect can further enhance the penetration absorption of active ingredients, especially water-soluble active ingredients when used together with bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate. In addition, rose oil itself is a good natural ingredient for beauty and skin care, and can also better penetrate and absorb when used with bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate. Therefore, the combination of rose oil and bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate provided by the present application not only enhances the penetration absorption of other active ingredients, but also enhances its own beauty and skin care efficacy, achieving multiple beauty care effects.

[0006] The present application provides a penetration-enhancing composition, which comprises the following components in a physiologically acceptable medium:

[0007] (a) bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate; and

[0008] (b) at least one rose flower oil;

[0009] The mass ratio of the component (a) to the component (b) is (0.1-2000):1.

[0010] In an optional embodiment, the mass ratio of component (a) to component (b) is (0.2-1000): 1. For example, it can be 0.1:1, 0.2:1, 0.5:1, 1:1, 10:1, 50:1, 100:1, 200:1, 300:1, 400:1, 500:1, 600:1, 700:1, 800:1, 900:1, 1000:1, 1100:1, 1200:1, 1300:1, 1400:1, 1500:1, 1600:1, 1700:1, 1800:1, 1900:1, 2000:1 or any value and range therebetween.

[0011] The amounts of bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate and rose flower oil to be used according to the invention can vary within wide limits to determine suitable amounts, depending on the desired cosmetic effect.

[0012] In an optional embodiment, the concentration of the bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate is 0.01-6wt% by weight of the composition. For example, it can be 0.01wt%, 0.05wt%, 0.1wt%, 0.2wt%, 0.3wt%, 0.4wt%, 0.5wt%, 0.6wt%, 0.7wt%, 0.8wt%, 0.9wt%, 1.0wt%, 1.1wt%, 1.2wt%, 1.3wt%, 1.4wt%, 1.5wt%, 1.6wt%, 1.7wt%, 1.8wt%, 1.9wt%, 2.0wt%, 2.1wt%, 2.2wt%, 2.3wt%, 2.4wt%, 2.5wt%, 2.6wt%, 2.7wt%, 2.8wt%, 2.9wt%, 3. 0wt%, 3.1wt%, 3.2wt%, 3.3wt%, 3.4wt%, 3.5wt%, 3.6wt%, 3.7wt%, 3.8wt%, 3.9wt%, 4.0wt%, 4.1wt%, 4.2wt%, 4.3wt%, 4.4wt%, 4.5wt%, 4.6wt%, 4.7wt%, 4.8wt%, 4.9wt%, 5.0wt%, 54.1wt%, 5.2wt%, 5.3wt%, 5.4wt%, 5.5wt%, 5.6wt%, 5.7wt%, 5.8wt%, 5.9wt%, 6.0wt% or any value and range therebetween.

[0013] In an optional embodiment, the concentration of the rose oil is 0.001-1wt% by weight of the composition. For example, it can be 0.001wt%, 0.002wt%, 0.003wt%, 0.004wt%, 0.005wt%, 0.006wt%, 0.007wt%, 0.008wt%, 0.009wt%, 0.01wt%, 0.02wt%, 0.03wt%, 0.04wt%, 0.05wt%, 0.06wt%, 0.07wt%, 0.08wt%, 0.09wt%. t%, 0.1wt%, 0.15wt%, 0.2wt%, 0.25wt%, 0.3wt%, 0.35wt%, 0.4wt%, 0.45wt%, 0.5wt%, 0.55wt%, 0.6wt%, 0.65wt%, 0.7wt%, 0.75wt%, 0.8wt%, 0.85wt%, 0.9wt%, 0.95wt%, 1.0wt% or any value and range therebetween.

[0014] Rose oil (INCI: ROSARUGOSAFLOWER OIL), its production methods include distillation, extraction, distillation extraction and the like.

[0015] Among them, the distillation method usually adopts distillation in water.

[0016] Among them, the extraction method is divided into organic solvent extraction, subcritical extraction and supercritical extraction. Organic solvent extraction is usually carried out at room temperature and pressure, and petroleum ether is generally used as the extraction medium. Supercritical extraction is carried out under the conditions of temperature exceeding the critical temperature and pressure exceeding the critical pressure, and carbon dioxide is usually used as the working medium. Subcritical extraction is carried out under the conditions of temperature and pressure being lower than the critical state, and butane is usually used as the medium.

[0017] Among them, the distillation extraction method combines steam distillation and solvent extraction into one, so that the sample vapor and solvent are fully integrated, repeatedly extracted, and volatile substances are obtained after concentration.

[0018] Rose oil can be purchased commercially or prepared at home.

[0019] In an optional embodiment, rose oil is prepared by itself: rose petals are distilled at high temperature using water as a solvent, and the water and oil are separated to obtain the oil phase to obtain rose oil.

[0020] In an optional embodiment, rose oil is prepared by itself: rose petals are distilled at high temperature using water as a solvent, condensed into a fractionating tower for water-oil separation to obtain an oil phase, and the oil phase is purified, impurities removed, and filtered to obtain rose oil.

[0021] In an alternative embodiment, the composition is an emulsion or a cream.

[0022] In an optional embodiment, the composition also includes an emulsifier. The application does not make any particular restrictions on the selection of emulsifier, as long as the aqueous phase and the oil phase can be evenly dispersed. It can be an emulsifier allowed to be used in the cosmetic field, and non-limiting examples that can be mentioned include the following emulsifiers: anionic surfactants, cationic surfactants, amphoteric surfactants, nonionic surfactants. The application does not make any particular restrictions on the use amount of emulsifier, and can be selected differently by those skilled in the art according to the knowledge they have mastered, depending on the application scenario.

[0023] As physiologically acceptable media, their composition, usage amount, etc. can be selected by those skilled in the art according to their knowledge and the type of application scenario required.

[0024] In addition to the above-mentioned components, the composition of the present application may also optionally contain preservatives, moisturizers, pH adjusters, functional additives, fragrances, pigments and other ingredients.

[0025] In a preferred embodiment, the emulsifier includes PPG-26-butanol polyether-26, PEG-40 hydrogenated castor oil, and the like.

[0026] The present application also provides the use of the above-mentioned composition as an osmotic absorption enhancer.

[0027] In an optional embodiment, it can act as an osmotic absorption enhancer to promote the osmotic absorption of water-soluble active ingredients and oil-soluble active ingredients.

[0028] In the present application, the water-soluble active ingredients that can be used include, but are not limited to, tranexamic acid (tranexamic acid), vitamin C and its derivatives, dipotassium glycyrrhizinate, hydrolyzed keratin, recombinant collagen, hydroxypropyl tetrahydropyrantriol, niacinamide, and the like.

[0029] In the present application, the oil-soluble active ingredients that can be used include, but are not limited to, phenethyl resorcinol, ethylhexyl ferulate, tocopherol and its derivatives, retinol and its derivatives, phytosterols, and the like.

[0030] In an alternative embodiment, the composition is applied to the skin or hair.

[0031] Preferably, the penetration-promoting effect of the composition as an osmotic absorption enhancer is achieved by promoting the transdermal absorption of the active ingredient.

[0032] The present application also provides the use of the above-mentioned composition in the preparation of cosmetics.

[0033] In an optional embodiment, the cosmetics may be essence, mask liquid, gel, lotion, foundation or cream. Those skilled in the art may add corresponding active ingredients, excipients or auxiliary materials according to the efficacy and type of the product.

[0034] Further, active ingredients (for example, water-soluble active ingredients, oil-soluble active ingredients) can be added, solvents (for example, water, oils, hexylene glycol, butylene glycol, 1,3-propylene glycol, etc.) can be added, moisturizers (for example, 1,2-pentanediol, tetrahydromethylpyrimidine carboxylic acid, hydrolyzed sodium hyaluronate, trehalose, Tremella fuciformis fruiting body extract, ethylhexylglycerol, sodium γ-polyglutamate, glycerol, butylene glycol, avocado oil, squalane, betaine, etc.) can be added, and thickeners (for example, glycerol, (acrylates / (C10-30) alkyl acrylate) cross-linked polymers, cellulose derivatives, xanthan gum, guar gum, starch and its derivatives, alginate and its derivatives, agar, sodium polyacrylate, carboxyvinyl polymers, bentonite, etc.) can be added. The excipients and adjuvants in the present application are not limited thereto, and those skilled in the art can add corresponding excipients or adjuvants according to the dosage form and area of ​​use.

[0035] The present application also provides a cosmetic composition, comprising the penetration-enhancing composition described above.

[0036] The present application also provides the use of rose oil in improving the penetration-enhancing effect of bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate.

[0037] The rose oil and bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate are defined as above.

[0038] The present invention has the following beneficial effects:

[0039] The present invention is the first to obtain a new high-efficiency penetration-promoting composition by combining bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate with rose oil which itself does not have a penetration-promoting effect. That is, it is the first to disclose that the two have a synergistic penetration-promoting effect, and the composition can effectively improve the penetration effect of the active ingredient. DETAILED DESCRIPTION

[0040] In order to more clearly illustrate the overall concept of the application, the following is described in detail by way of embodiment. In the following description, a large amount of specific details are provided to provide a more thorough understanding of the present invention. However, it is obvious to those skilled in the art that the present invention can be implemented without one or more of these details. In other examples, in order to avoid confusion with the present invention, some technical features well known in the art are not described.

[0041] If no specific conditions are specified in the examples, the experiments were carried out according to conventional conditions or conditions recommended by the manufacturer.

[0042] Among them, the rose (ROSARUGOSA) flower oil 1 used in this application was purchased from Zhenjiang Tanyuan Essential Oil Trading Co., Ltd., with the trade name rose oil and batch number 2024030990; rose (ROSA RUGOSA) flower oil 2 was purchased from Zhenjiang Tanyuan Essential Oil Trading Co., Ltd., with the trade name DARK ROSE OIL and batch number TY24030660; bitter orange (CITRUS AURANTIUM AMARA) flower oil was purchased from Zhenjiang Tanyuan Essential Oil Trading Co., Ltd., bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate was purchased from NIPPON FINECHEMICAL CO., LTD., and PPG-26-butanol polyether-26 and PEG-40 hydrogenated castor oil were purchased from Beijing Huaxia Miaosen Biotechnology Co., Ltd.

[0043] Unless otherwise specified, in the following embodiments, the reagents or instruments used without indicating the manufacturer are all conventional products that can be purchased commercially.

[0044] In addition, the "water" mentioned in the present invention includes any feasible water that can be used in the art, such as deionized water, distilled water, ion exchange water, double distilled water, high-purity water, and purified water.

[0045] In the following examples, unless otherwise specified, % means wt %, i.e. weight percentage.

[0046] Example

[0047] In this example, a Franz diffusion cell permeability test was used to examine the skin's ability to absorb the sample in order to find a combination of effective ingredients that promotes absorption. The specific method is as follows:

[0048] This example is based on a suckling pig skin-Franz cell diffusion cell system, and a Franz diffusion cell permeability experiment was performed on different samples using suckling pig back skin.

[0049] The in vitro test method for chemical skin absorption is to simulate the distribution and absorption of the test substance in the skin. By adding the supply liquid and collecting the receiving liquid, the state of the skin and subcutaneous tissue after applying the sample is simulated, and the penetration of the sample into the skin after 24 hours is examined. Set up the test group and the control group to consider the test conditions of the samples with different treatments. Transaminase is used to represent the water-soluble active ingredient.

[0050] 1. Test samples

[0051] Control group sample: tranexamic acid was dissolved in water to obtain a 2 wt % tranexamic acid aqueous solution.

[0052] Test group samples: tranexamic acid was dissolved in the test example or comparative example solution to obtain a 2 wt % tranexamic acid solution.

[0053] Test example or comparative example solution preparation method:

[0054] Test Example 1-10

[0055] Add ROSARUGOSA flower oil 1 into 0.9 g PPG-26-butaneth-26 and dissolve completely;

[0056] At 80°C, add bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate to an appropriate amount of purified water, stir evenly until completely dissolved, and after cooling to room temperature, add pre-dissolved PPG-26-butanol polyether-26 and rose (ROSARUGOSA) flower oil 1, add the composition to 100g, stir until completely dissolved, and obtain a penetration-promoting composition.

[0057] The specific contents of bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate and rose (ROSA RUGOSA) flower oil 1 are shown in Table 1.

[0058] Test Example 11

[0059] The only difference between Test Example 11 and Test Example 1 is that PEG-40 hydrogenated castor oil is used to replace PPG-26-butanediol polyether-26.

[0060] Test Example 12

[0061] The only difference between Test Example 12 and Test Example 1 is that Rose (ROSARUGOSA) flower oil 2 is used to replace Rose (ROSARUGOSA) flower oil 1.

[0062] Comparative Examples 1-6

[0063] At 80° C., bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate was added to an appropriate amount of purified water, stirred evenly until completely dissolved, added with water to 100 g, and cooled to room temperature to obtain the composition of Comparative Examples 1-6.

[0064] Comparative Examples 7-8

[0065] 1 rose (ROSARUGOSA) flower oil was added into 0.9 g of PPG-26-butanol polyether-26 to completely dissolve, water was added to 100 g, and the mixture was stirred until completely dissolved to obtain the composition of Comparative Examples 7-8.

[0066] Comparative Example 9

[0067] 0.9 g of PPG-26-butanol polyether-26 was added to an appropriate amount of purified water to completely dissolve, the water was added to 100 g, and the mixture was stirred until completely dissolved to obtain the composition of Comparative Example 9.

[0068] Comparative Example 10

[0069] The only difference between Comparative Example 10 and Test Example 1 is that bitter orange (CITRUS AURANTIUM AMARA) flower oil is used instead of rose (ROSARUGOSA) flower oil 1.

[0070] Comparative Example 11

[0071] The only difference between Comparative Example 11 and Test Example 3 is that bitter orange (CITRUS AURANTIUM AMARA) flower oil is used instead of rose (ROSARUGOSA) flower oil 1.

[0072] Comparative Example 12

[0073] The only difference between Comparative Example 12 and Test Example 1 is that the content of Rose (ROSA RUGOSA) flower oil 1 is different.

[0074] 2. Test methods

[0075] Skin Information: Whole back skin of suckling pig.

[0076] Instrument and equipment: Absorption-diffusion tester (TK-12D).

[0077] Effective exposure area: 2cm 2 .

[0078] Receiving fluid: saline.

[0079] Total exposure time: 24h.

[0080] 3. Test process

[0081] 3.1 Device preparation

[0082] Place the matching magnetic stirrer in the receiving tank, and fix the pig skin between the supply tank and the receiving tank. After fixation, add 8 mL of physiological saline solution into the receiving tank, exhaust the air, and make the bottom surface of the pig skin in close contact with the receiving solution.

[0083] 3.2 Skin contamination

[0084] Test group: 4 μL of the test group sample was evenly added to the pig skin surface. Three groups of parallel samples were set up and stirred continuously at a constant speed of 300 r / min in a (32±1)℃ constant temperature water bath.

[0085] Control group: 4 μL of the control group sample was evenly added to the pig skin surface. Three parallel groups of samples were set up and stirred continuously at a constant speed of 300 r / min in a (32±1)℃ constant temperature water bath.

[0086] 3.3 Analytical sample preparation

[0087] (1) Preparation of skin samples

[0088] After 24 hours of infiltration, anhydrous methanol solution was sucked up with a pipette and repeatedly blown to clean the surface of the suckling pig skin. Wash 3 times and adjust the volume to 2.0 mL.

[0089] (2) Preparation of skin samples

[0090] After 24 h of infiltration, the suckling pig skin was cut into pieces and placed in a 2.0 mL EP tube, and the volume was adjusted to 2.0 mL with anhydrous methanol and ultrasonicated for 30 min.

[0091] (3) Preparation of subcutaneous samples

[0092] At the 24-h penetration time point, 1.0 mL of receiving solution was extracted through a Peek tube connected to a pipette and placed in a 2.0 mL EP tube.

[0093] 3.4 Instrumental analysis

[0094] The tranexamic acid content of each sample was quantitatively analyzed by liquid chromatography-mass spectrometry (LC-MS).

[0095] 4. Data and analysis

[0096] 24h diffusion percentage (%) = (skin content + subcutaneous content) / sample amount × 100%.

[0097] Loading amount = concentration × loading volume.

[0098] 5. The test results are shown in Table 2.

[0099] The t test was used for pairwise comparison. P>0.05 indicates no statistical difference (ns), *P<0.05 indicates statistical difference, **P<0.01 indicates significant statistical difference, and ***P<0.001 indicates extremely significant statistical difference.

[0100] Table 1

[0101]

[0102]

[0103] Table 2 Transeam acid skin absorption 24h diffusion percentage

[0104]

[0105]

[0106] It can be seen from the results in Table 2 that the 24h diffusion percentage of Test Examples 1-12 is significantly higher than that of the corresponding Comparative Examples 1-6, which indicates that the combination of bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate and rose (ROSA RUGOSA) flower oil without a permeation-promoting effect enhances the permeation effect of the target ingredient (tranexamic acid) and plays a synergistic role in promoting permeation.

[0107] The above is only an embodiment of the present application and is not intended to limit the present application. For those skilled in the art, the present application may have various changes and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application should be included in the scope of the claims of the present application.

Claims

1. A penetration-enhancing composition, characterized in that The composition comprises the following components in a physiologically acceptable medium: (a) bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate; and (b) at least one rose flower oil; The mass ratio of the component (a) to the component (b) is (0.1-2000):

1.

2. The composition according to claim 1, characterized in that Calculated by weight percentage of the composition, the concentration of the bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate is 0.01-6 wt %.

3. The composition according to claim 1, characterized in that The composition is an emulsion or a cream.

4. Use of the composition according to any one of claims 1 to 3 as an osmotic absorption enhancer.

5. The use according to claim 4, characterized in that: The composition is applied to the skin or hair.

6. Use of the composition according to any one of claims 1 to 3 in the preparation of cosmetics.

7. A cosmetic composition comprising the penetration-enhancing composition according to any one of claims 1 to 3.

8. Application of rose oil in improving the penetration-enhancing effect of bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate.

9. The use according to claim 8, wherein the mass ratio of the rose oil to bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate is (0.1-2000):1.

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