Application of caffeine penetration enhancer, retinol and / or retinol ester derivative and skin external product

Abstract

The embodiment of the invention discloses application of a caffeine penetration enhancer, retinol and / or a retinol ester derivative and a skin external product. The caffeine penetration enhancer comprises retinol and / or a retinol ester derivative, the mass ratio of the caffeine to the retinol is 1: (0.2-1), and the mass ratio of the caffeine to the retinol ester derivative is 1: (0.2-1). The caffeine penetration enhancer can effectively promote the skin penetration of caffeine.

Description

Technical Field

[0001] Embodiments of the present disclosure relate to the field of biotechnology, and in particular to uses of caffeine penetration enhancers, retinol and / or retinol ester derivatives, and topical skin products. Background Art

[0002] Caffeine, chemical formula is C 8 H 10 N 4 O 2 , is a natural xanthine alkaloid compound, mainly found in the fruits and leaves of coffee trees, tea trees, and Brazilian cocoa. In addition, caffeine is also a central nervous system stimulant with a refreshing effect. In skin care, caffeine is widely used in anti-oxidation, promoting blood circulation, reducing edema, stimulating hair growth, and eliminating skin dullness. In beauty, because it can inhibit the activity of phosphodiesterase, it stimulates fat degradation during the fat decomposition process, that is, it can prevent excessive accumulation of fat in cells, so it is often used as an active compound in fat-reducing products.

[0003] However, caffeine often has the following technical problems in skin care and beauty:

[0004] Due to the existence of the skin's natural barrier and the physical and chemical properties of caffeine itself, the permeability of caffeine in the skin is limited, affecting the effectiveness of caffeine.

[0005] The above information disclosed in this Background section is only for enhancement of understanding of the background of the inventive concept and therefore it may contain information that does not form the prior art that is already known to a person of ordinary skill in the art. Summary of the invention

[0006] The content of this disclosure is used to introduce concepts in a brief form, which will be described in detail in the detailed implementation section below. The content of this disclosure is not intended to identify the key features or essential features of the technical solution claimed for protection, nor is it intended to limit the scope of the technical solution claimed for protection.

[0007] Some embodiments of the present disclosure propose uses of caffeine penetration enhancers, retinol and / or retinol ester derivatives, and skin topical products to solve one or more of the technical problems mentioned in the above background technology section.

[0008] In a first aspect, some embodiments of the present disclosure provide a caffeine penetration enhancer, comprising: retinol and / or retinol ester derivatives, wherein the mass ratio of caffeine to the above retinol is 1:0.2-1, and the mass ratio of the above caffeine to the above retinol ester derivative is 1:0.2-1.

[0009] Optionally, the retinol ester derivative is an ester-soluble derivative of retinol.

[0010] Optionally, the above-mentioned retinol ester derivative is one or more of retinol palmitate, hydroxypinacolone retinoic acid ester, retinol acetate, retinol linoleate, retinol propionate, retinol retinoic acid ester, and hydroxypinacolone retinoic acid ester.

[0011] Optionally, the retinol ester derivative is one or more of retinol palmitate and / or hydroxypinacolone retinoic acid ester.

[0012] Optionally, the added amount of the caffeine is 0.1% to 2%.

[0013] Optionally, the added amount of the retinol or retinol ester derivative is 0.01% to 0.6%.

[0014] In a second aspect, some embodiments of the present disclosure provide a use of retinol and / or retinol ester derivatives, which includes the use of the caffeine penetration enhancer as described above in the first aspect to promote the skin penetration of caffeine.

[0015] In a third aspect, some embodiments of the present disclosure provide a skin external product, wherein the skin external product comprises the caffeine penetration enhancer and caffeine as described above in the first aspect.

[0016] Optionally, the above-mentioned skin external product includes: one or more of: water-based solution, emulsion, cream, ointment.

[0017] Optionally, the aqueous solution may include one or more of skin care lotion, toner, and essence.

[0018] Optionally, the emulsion may include: an emulsion.

[0019] Optionally, the cream may include: a facial cream, wherein the facial cream may be a facial cream with a transparent texture or a facial cream with a non-transparent texture.

[0020] Optionally, the ointment may include: a skin care ointment.

[0021] The above-mentioned embodiments of the present disclosure have the following beneficial effects: the caffeine penetration enhancer of some embodiments of the present disclosure includes retinol and / or retinol ester derivatives, wherein the mass ratio of caffeine to the above-mentioned retinol is 1:0.2 to 1, and the mass ratio of the above-mentioned caffeine to the above-mentioned retinol ester derivative is 1:0.2 to 1. The caffeine penetration enhancer of the present disclosure can effectively promote the skin penetration of caffeine. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] The above and other features, advantages and aspects of the embodiments of the present disclosure will become more apparent with reference to the following detailed description in conjunction with the accompanying drawings. Throughout the accompanying drawings, the same or similar reference numerals represent the same or similar elements. It should be understood that the drawings are schematic and the elements are not necessarily drawn to scale.

[0023] Figure 1 is a comparison chart of the retention amounts of the epidermis layer + dermis layer of samples A to E in some embodiments of the present disclosure in 24 hours;

[0024] Figure 2 is a comparison chart of the cumulative permeation of samples A to E in some embodiments of the present disclosure in 24 hours;

[0025] Figure 3 is a comparison chart of the retention of the epidermis layer + dermis layer in 24 hours of sample A, sample F, sample G and sample H of some embodiments of the present disclosure;

[0026] Figure 4 This is a comparison chart of the cumulative permeation of sample A, sample F, sample G and sample H in some embodiments of the present disclosure within 24 hours. DETAILED DESCRIPTION

[0027] Embodiments of the present disclosure will be described in more detail below with reference to the accompanying drawings. Although certain embodiments of the present disclosure are shown in the accompanying drawings, it should be understood that the present disclosure can be implemented in various forms and should not be construed as being limited to the embodiments set forth herein. On the contrary, these embodiments are provided to provide a more thorough and complete understanding of the present disclosure. It should be understood that the drawings and embodiments of the present disclosure are only for exemplary purposes and are not intended to limit the scope of protection of the present disclosure.

[0028] It should also be noted that, for ease of description, only the parts related to the invention are shown in the drawings. In the absence of conflict, the embodiments and features in the embodiments of the present disclosure can be combined with each other.

[0029] It should be noted that the modifications of "one" and "plurality" mentioned in the present disclosure are illustrative rather than restrictive, and those skilled in the art should understand that unless otherwise clearly indicated in the context, it should be understood as "one or more".

[0030] It should be noted that the term “about” mentioned in the present disclosure, when used to define a numerical value, means ±5% of the specified numerical value.

[0031] It should be noted that the term "%" mentioned in the present disclosure means mass % unless otherwise specified.

[0032] It should be noted that the "normal temperature" mentioned in the present disclosure refers to the ambient temperature, that is, no special heating or cooling treatment has been performed.

[0033] The term "retinol" refers to a derivative of vitamin A with a chemical formula of C 20 H 30 O is a fat-soluble vitamin, which is widely used in the field of skin care. Specifically, it can act on the skin epidermis to promote cell reproduction, maintain normal skin circulation, repair lost collagen, reduce wrinkles, and relieve signs of premature aging (such as abnormal pigmentation, rough spots and dry skin).

[0034] The term "retinyl palmitate" is an ester obtained by combining retinol with palmitic acid, wherein retinyl palmitate is a saturated fatty acid that is chemically stable and easily absorbed by the skin.

[0035] The term "hydroxypinacolone retinoic acid ester" is an ester of retinol and pinacol.

[0036] The term "paraformaldehyde" refers to a polymer of formaldehyde, the chemical formula of which is (CH 2 O) n , where n is 8 to 100.

[0037] The term "polyethylene glycol 400", also known as PEG400, is a non-ionic inert solvent and a colorless viscous liquid at room temperature.

[0038] The term "anhydrous ethanol" refers to an ethanol aqueous solution with a relatively high purity, wherein the concentration of anhydrous ethanol is ≥ 99.5%.

[0039] The term "1,2-hexanediol" is an organic compound with the chemical formula C 6 H 14 O 2 .

[0040] The term "PBS", also known as phosphate buffered saline, is a mixture of water and salt. Specifically, standard PBS is usually composed of sodium chloride, potassium chloride, sodium dihydrogen phosphate and disodium hydrogen phosphate, wherein the pH value of PBS is between 7-7.4.

[0041] The term "stratum corneum" refers to the outermost layer of the epidermis, which is mainly composed of 15 to 20 layers of dead cells without nuclei. The cells in the stratum corneum contain keratin, which can absorb water to keep the skin moist.

[0042] The term "epidermis" refers to the outer layer of the skin, which is formed by the ectoderm during the embryonic period. The epidermis is composed of the stratum corneum, the stratum lucidum, the stratum granulosum, the stratum spinosum, and the stratum basale.

[0043] The term "dermis" refers to a layer of skin located between the epidermis and the subcutaneous tissue, which is composed of the papillary layer and the reticular layer. Among them, the dermis is composed of collagen, elastic fibers and matrix.

[0044] The present disclosure will be described in detail below with reference to the accompanying drawings and in conjunction with embodiments.

[0045] Experimental equipment description

[0046] The relevant description of the experimental equipment is shown in Table 1 below:

[0047] Table 1

[0048]

[0049] Experimental Materials Description

[0050] The relevant description of the experimental materials is shown in Table 2 below:

[0051] Table 2

[0052]

[0053] Experimental method description

[0054] In vitro permeation experiments were conducted using Franz transdermal diffusion cells to observe the in vitro permeation of caffeine in different samples on the skin of Bama miniature pigs and the retention of caffeine in different skin layers. The effective diffusion area of ​​the Franz transdermal diffusion cell is 1.54 m 2 , the volume of the receiving solution is 8 mL. Specifically, the experiment includes the following steps:

[0055] In the first step, fresh skin samples (Bama miniature pig skin) were fixed between the receiving tank and the donor tank.

[0056] The stratum corneum of the skin sample was facing upward.

[0057] In the second step, 0.5 mL of samples (samples A to G) were placed in the supply cells respectively and sealed with plastic wrap to prevent the solution from evaporating.

[0058] PBS / anhydrous ethanol (v / v, 70 / 30) was used as the diffusion medium of the receiving cell. During the test, the diffusion medium was kept at 32°C and stirred at 350 rpm. Four copies of each sample (sample A to sample G) were set in parallel.

[0059] In the third step, 1 mL of the receptor solution was withdrawn at predetermined time intervals (2 hours, 4 hours, 8 hours, 12 hours, and 24 hours) and supplemented with the same volume of preheated fresh receptor solution.

[0060] In the fourth step, after 20 hours, the skin tissue corresponding to each sample was collected and fixed in 4% paraformaldehyde for 24 hours, and then dehydrated in 15% and 30% sucrose solutions respectively after 24 hours until the skin tissue sank to the bottom, then washed with PBS, and the skin tissue was embedded in 10% CMC-Na and stored frozen.

[0061] The fifth step is to use a freezing microtome to cross-section the skin of the transdermal area into stratum corneum (0-20 μm), epidermis + dermis (the stratum corneum is removed from the transdermal area).

[0062] Step 6: Cut the stratum corneum, epidermis + dermis into pieces respectively, and weigh them after cutting.

[0063] Step 7. After weighing, the stratum corneum fragments and the epidermis + dermis fragments were subjected to water ultrasonic treatment for 1 hour respectively.

[0064] Step 8. After 20 hours, the remaining sample solution in the supply pool was recovered, the recovery rate was calculated, the drug content in the receiving pool at different time points was determined by HPLC (high performance liquid chromatography), the transdermal permeation curve was drawn, and the retention of caffeine in different skin layers was calculated.

[0065] The liquid phase method includes: mobile phase: (water: methanol = 50:50), flow rate 1.0 mL / min; detection wavelength: 275 nm; column temperature: 30°C.

[0066] Statistical methods

[0067] Prism 8.0 was used for data analysis, and statistical analysis was expressed as (x±s) and t-test was performed. P<0.05 was used as the test level, *p<0.05, **p<0.01.

[0068] Example Description

[0069] Among them, sample A, sample B, sample C, sample D, sample E, sample F, sample G, and sample H were prepared. The specific concentration ratios of caffeine and penetration enhancer in each sample are shown in Table 3 below:

[0070] Table 3

[0071]

[0072] The retention and cumulative penetration of caffeine in the epidermis + dermis corresponding to samples A to E are shown in Table 4 below:

[0073] Table 4

[0074]

[0075]

[0076] Combined with Table 4, Figure 1 The comparison of the retention of samples A to E in the epidermis + dermis after 24 hours is shown, and Figure 2 The comparison chart of the cumulative permeation of samples A to E in 24 hours shows that, firstly, compared with sample A (caffeine alcohol solution), samples B to E have significantly increased the 24-hour skin permeation and retention of caffeine after adding different concentrations of retinol. In addition, with the increase of retinol concentration, the 24-hour permeation is also higher than that of sample A (caffeine alcohol solution), especially sample C (0.4% retinol) has a significant increase. In summary, retinol can be used as a penetration enhancer to significantly promote the skin permeation of caffeine and increase the retention of caffeine.

[0077] The retention and cumulative penetration of caffeine in the epidermis + dermis corresponding to Sample A, Sample F and Sample G are shown in Table 5 below:

[0078] Table 5

[0079]

[0080] Combined with Table 5, Figure 3 The comparison of the retention of sample A, sample F and sample G in the epidermis + dermis after 24 hours is shown, and Figure 4 The comparison chart of the cumulative permeation of samples A, F and G in 24 hours shows that, firstly, compared with sample A, after adding 0.2% and 0.3% of retinol palmitate to samples F and G respectively, the 24-hour skin permeation and retention of caffeine also increased significantly. In particular, when the addition amount of retinol palmitate was 0.3%, there was a significant improvement. In addition, by comparing the experimental results of samples A and H, it can be seen that after adding hydroxypinacolone retinoic acid ester to sample H, the 24-hour skin permeation and retention of caffeine also increased significantly; and under the same addition amount, the 24-hour skin permeation and retention of caffeine in sample H with hydroxypinacolone retinoic acid ester increased more significantly than that in sample F with retinol palmitate. It can be seen that hydroxypinacolone retinoic acid ester performs better than retinol palmitate in promoting the penetration of caffeine. In summary, retinyl palmitate can also be used as a penetration enhancer that significantly promotes caffeine skin penetration and increases caffeine retention.

[0081] Application Example 1 The components of the product prepared in Application Example 1 are shown in Table 6 below:

[0082] Table 6

[0083] Mutually Component name Mass fraction (%) A Deionized water TO 100 A Dipropylene glycol 7 A p-Hydroxyacetophenone 0.5 A Hexanediol 0.5 A EDTA-2Na 0.05 A Ammonium Acryloyldimethyltaurate / VP Copolymer 0.5 A caffeine 1 B Isononyl Isononanoate 6 B PEG-100 Stearate, Glyceryl Stearate 2 B Tocopheryl acetate 0.3 B Polydimethylsiloxane 1.5 C Retinyl palmitate 0.3

[0084] Preparation method:

[0085] The first step is to add the corresponding components of A into the emulsification tank, set the temperature to 80-90℃, start stirring and heating. When the emulsification tank is heated to 80-90℃, start homogenization at 1500-4000r / min until there are no lumps in the material.

[0086] The second step is to mix the corresponding components of B in the oil phase pot and heat to 75-80°C. After the corresponding components of B are completely dissolved, add the corresponding components of B into the emulsification tank, keep stirring, and start cooling after they are evenly dispersed.

[0087] In the third step, the emulsification tank is continuously stirred and cooled to 45°C. The corresponding components of C are dissolved and added into the emulsification pot. The temperature is lowered and the material is discharged when the temperature is 30-38°C.

[0088] Application Example 2

[0089] The components of the product prepared in Application Example 2 are shown in Table 7 below:

[0090] Table 7

[0091] Mutually Component name Mass fraction (%) A Deionized water TO 100 A Dipropylene glycol 7 A p-Hydroxyacetophenone 0.5 A Hexanediol 0.5 A EDTA-2Na 0.05 A Ammonium Acryloyldimethyltaurate / VP Copolymer 0.5 A caffeine 1 B Isononyl Isononanoate 6 B PEG-100 Stearate, Glyceryl Stearate 2 B Tocopheryl acetate 0.3 B Polydimethylsiloxane 1.5 C Retinol 0.2

[0092] Preparation method:

[0093] The first step is to add the corresponding components of A into the emulsification tank, set the temperature to 80-90℃, start stirring and heating. When the emulsification tank is heated to 80-90℃, start homogenization at 1500-4000r / min until there are no lumps in the material.

[0094] The second step is to mix the corresponding components of B in the oil phase pot and heat to 75-80°C. After the corresponding components of B are completely dissolved, add the corresponding components of B into the emulsification tank, keep stirring, and start cooling after they are evenly dispersed.

[0095] In the third step, the emulsification tank is continuously stirred and cooled to 45°C. The corresponding components of C are dissolved and added into the emulsification pot. The temperature is lowered and the material is discharged when the temperature is 30-38°C.

[0096] Application Example 3

[0097] The components of the product prepared in Application Example 3 are shown in Table 8 below:

[0098] Table 8

[0099] Mutually Component name Mass fraction (%) A Deionized water TO 100 A Dipropylene glycol 7 A p-Hydroxyacetophenone 0.5 A Hexanediol 0.5 A EDTA-2Na 0.05 A Ammonium Acryloyldimethyltaurate / VP Copolymer 0.5 A caffeine 1 B Isononyl Isononanoate 6 B PEG-100 Stearate, Glyceryl Stearate 2 B Tocopheryl acetate 0.3 B Polydimethylsiloxane 1.5 C Hydroxypinacolone retinoate 0.2

[0100] Preparation method:

[0101] The first step is to add the corresponding components of A into the emulsification tank, set the temperature to 80-90℃, start stirring and heating. When the emulsification tank is heated to 80-90℃, start homogenization at 1500-4000r / min until there are no lumps in the material.

[0102] The second step is to mix the corresponding components of B in the oil phase pot and heat to 75-80°C. After the corresponding components of B are completely dissolved, add the corresponding components of B into the emulsification tank, keep stirring, and start cooling after they are evenly dispersed.

[0103] In the third step, the emulsification tank is continuously stirred and cooled to 45°C. The corresponding components of C are dissolved and added into the emulsification pot. The temperature is lowered and the material is discharged when the temperature is 30-38°C.

[0104] The above descriptions are only some preferred embodiments of the present disclosure and an explanation of the technical principles used. Those skilled in the art should understand that the scope of the invention involved in the embodiments of the present disclosure is not limited to the technical solutions formed by a specific combination of the above-mentioned technical features, but should also cover other technical solutions formed by any combination of the above-mentioned technical features or their equivalent features without departing from the above-mentioned inventive concept. For example, the above-mentioned features are replaced with the technical features with similar functions disclosed in the embodiments of the present disclosure (but not limited to) and the technical solutions formed.

Claims

1. A caffeine penetration enhancer, comprising: Retinol and / or retinol ester derivatives, wherein the mass ratio of caffeine to the retinol is 1:0.2-1, and the mass ratio of caffeine to the retinol ester derivative is 1:0.2-1.

2. The caffeine penetration enhancer according to claim 1, wherein The retinol ester derivatives include: one or more of retinol palmitate, hydroxypinacolone retinoic acid ester, retinol acetate, retinol linoleate, retinol propionate, and retinol retinoic acid ester.

3. The caffeine penetration enhancer according to claim 1, wherein The retinol ester derivatives include: one or more of retinol palmitate and hydroxypinacolone retinoic acid ester.

4. The caffeine penetration enhancer according to claim 1, wherein The added amount of caffeine is 0.1% to 2%.

5. The caffeine penetration enhancer according to claim 1, wherein The added amount of the retinol or retinol ester derivative is 0.01% to 0.6%.

6. Use of retinol and / or retinol ester derivatives, comprising use of retinol and / or retinol ester derivatives in the preparation of the caffeine penetration enhancer according to any one of claims 1 to 5.

7. A skin external product, wherein: The skin external product comprises the caffeine penetration enhancer according to any one of claims 1 to 5 and caffeine.

8. The skin external product according to claim 7, wherein The skin external product includes: one or more of water-based solutions, emulsions, creams, and ointments.

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