CN114588067A - Hydroxy pinacolone retinoic acid ester high-oil permeation-promoting carrier, preparation method and application thereof - Google Patents
Hydroxy pinacolone retinoic acid ester high-oil permeation-promoting carrier, preparation method and application thereof Download PDFInfo
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- CN114588067A CN114588067A CN202210270727.6A CN202210270727A CN114588067A CN 114588067 A CN114588067 A CN 114588067A CN 202210270727 A CN202210270727 A CN 202210270727A CN 114588067 A CN114588067 A CN 114588067A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/671—Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/345—Alcohols containing more than one hydroxy group
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/37—Esters of carboxylic acids
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4993—Derivatives containing from 2 to 10 oxyalkylene groups
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/55—Phosphorus compounds
- A61K8/553—Phospholipids, e.g. lecithin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/676—Ascorbic acid, i.e. vitamin C
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- A—HUMAN NECESSITIES
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- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
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Abstract
The application provides a hydroxy pinacolone retinoic acid ester high oil permeation-promoting carrier, a preparation method and application thereof, wherein the hydroxy pinacolone retinoic acid ester is dissolved by a large amount of oil and then wrapped in lipid spheres formed by phosphatidylcholine and polysorbate-80, the oil and polysorbate-80 in a specific ratio can regulate and control the deformability of a membrane material, so that the membrane material obtains higher permeability, and furthermore, the skin-friendly property and lipophilicity of the phosphatidylcholine and isononyl isononanoate enable HPR to be more easily retained in a skin layer after penetrating through a horny layer and not to easily penetrate through a dermis layer to enter blood circulation.
Description
Technical Field
The invention relates to the field of cell biology, in particular to a hydroxy pinacolone retinoic acid ester high-oil permeation-promoting carrier, a preparation method and application thereof.
Background
As a new generation of anti-aging component of the vitamin a family, hydroxy pinacolone retinoic acid ester (HPR) has unique properties, mainly due to its specific chemical structure. Structurally, HPR is the product of the esterification reaction of retinoic acid and pinacol, a substance that has the advantages of tretinoin and tretinoin esters. When the cell retinoic acid receptor RAR is combined with HPR, the cell retinoic acid receptor RAR can promote cell proliferation, biosynthesis of extracellular proteins and polysaccharides, improve cell metabolism and other processes, and can achieve the effects of resisting wrinkles and reducing wrinkles.
The stratum corneum has a dense brick wall structure that severely restricts the ingress of foreign matter. HPR is a strong fat-soluble substance, hardly soluble in water and easily precipitated in the product, and thus has very low transdermal efficiency.
The conventional penetration-promoting methods at present mainly include chemical penetration-promoting agents, physical penetration-promoting agents such as iontophoresis, microneedles, etc., which have high requirements for equipment and may damage the stratum corneum of skin, and thus it is more common in cosmetics to achieve penetration-promoting of HPR using chemical penetration-promoting agents, for example, patent No. cn202110473784.x discloses a polyol composition comprising: panthenol, 1, 2-propanediol, 1, 3-propanediol, and polyethylene glycol. The polyol composition further comprises any one or combination of at least two of glycerin, butanediol or 1, 2-hexanediol, the polyol composition is added to skin care bases with different efficacies, can remarkably improve the problem of percutaneous absorption of skin care functional components, improve the efficacy of the product, simultaneously, the absorbability and the moisture retention of the product are improved, the smearing feeling and the sticky feeling of the product are improved, the polyol composition is used to improve transdermal absorption of actives including HPR, but in view of known solutions, the solubility of HPR in these polyols is low, high loading levels are difficult to achieve, and the use of the polyols can have the problems of heat sensation and irritation, and most importantly, the polyols such as propylene glycol are mainly used for percutaneous absorption of the medicine, but not for skin residence, and the introduction of a percutaneous penetration enhancer can cause systemic irritation risk.
Patent cn202010359684.x discloses a: an anti-aging nano composition comprises the following components in percentage by mass: 0.1-15% of fat-soluble anti-aging active ingredients, 0.1-20% of water-soluble anti-aging active ingredients, 1-15% of emulsifying agents, 3-30% of co-emulsifying agents and the balance of deionized water, has good targeting and transdermal absorption effects, increases the solubility and stability of each ingredient, saves the using amount of functional ingredients, reduces the cost, and provides a more comprehensive and effective anti-aging product for consumers; patent CN201910811369.3 discloses a preparation method and application of a vitamin a nano inclusion, wherein the nano inclusion specifically comprises the following components: vitamin A1-10%; 2-70% of glycerol; 1-10% of phospholipid; 1-10% of antioxidant; 1-25% of grease; emulsifier 1-15%, water to 100%. Patent CN202110175444.9 discloses a multi-effect hydroxy pinacolone retinoic acid ester nano composition and a preparation method thereof, the nano composition comprises hydroxy pinacolone retinoic acid ester, nicotinamide, glycyrrhetinic acid, an emulsifier, an auxiliary emulsifier and polyhydric alcohol, the three functional components of the nano composition are reasonably matched, synergized and enter deep tissues of skin through skin barriers, bioavailability is improved, and anti-aging, acne-removing and whitening effects are improved.
However, the currently reported research scheme is only 2-3 times that of the comparative example, even under the optimal condition. The problems of insufficient penetration promoting effect, even complete loss and the like generally exist when the nano composition is added into an actual cosmetic finished product. From multiple permeation experiments of experimenters in the scheme, when the nano-component is added into cosmetics for permeation promotion, strict requirements are imposed on the type, proportion and addition mode of auxiliary materials, small changes of content, particle size, zeta potential, addition mode and the like can bring completely different effects, special formula design and screening are needed for specific active substances to achieve high retention amount in skin, the selectable modes comprise liposome, liposome analogs for permeation promotion in different modes, nano-emulsion/micro-emulsion, cyclodextrin, ion permeation promotion, permeation promoter combination and the like, and most of the technologies have wide description on the type and proportion of nano-compositions for achieving high HPR (high skin retention rate).
Disclosure of Invention
The invention firstly provides a composition for promoting skin permeation of hydroxy pinacolone retinoic acid ester, aims to solve the problems of low skin retention rate, unstable permeation promoting effect and the like existing in the existing application scheme of hydroxy pinacolone retinoic acid ester, and provides a transfersome capable of assisting transdermal absorption of hydroxy pinacolone retinoic acid ester (HPR), so that the invention provides a hydroxy pinacolone retinoic acid ester high-oil permeation promoting transfersome which is characterized by comprising the following components in percentage by mass: 38-40% of glycerin, 26-31% of water, 19-21% of isononyl isononanoate, 3-6% of phosphatidylcholine, 804-7% of polysorbate, 1.9-2.1% of hydroxyppinacolone retinoic acid ester, 0.0004-0.012% of ascorbyl palmitate and 0.0004-0.012% of tocopherol. The water is deionized water.
The beneficial effects of adopting the above technical scheme are:
the transfersome has the characteristics of high skin retention rate, high stability and the like, can greatly improve the anti-wrinkle effect of the hydroxy pinacolone retinoic acid ester in a cosmetic formula, and particularly, the hydroxy pinacolone retinoic acid ester is dissolved by a large amount of grease and then wrapped in a lipid sphere formed by phosphatidylcholine and polysorbate-80, and the grease and polysorbate-80 in a specific ratio can regulate the deformation capacity of a membrane material, so that the membrane material obtains higher permeability. The skin permeation test result shows that the skin retention rate of some skin care product formulas prepared by using the composition is obviously higher than that of a control group (HPR common essence emulsion), the skin retention rate of the skin care product formulas can reach more than 8 times of that of the control group, and HPR is not detected in a receiving pool, which indicates that the HPR essence prepared by using the scheme can promote permeation and simultaneously can not cause HPR to enter blood circulation.
Preferably, the ratio of the ascorbyl palmitate to the tocopherol is as follows: 1: 1-1: 3.
the invention also provides a preparation method of the hydroxy pinacolone retinoic acid ester high-oil permeation-promoting carrier, which is characterized by comprising the following steps of:
step (1): weighing isononyl isononanoate 19-21%, phosphatidylcholine 3-6%, polysorbate-80 4-7%, ascorbyl palmitate 0.0004-0.012%, and tocopherol, and heating and stirring in water bath at 50-80 deg.C to completely dissolve phosphatidylcholine to obtain uniform solution;
step (2): weighing 1.9-2.1% of hydroxy pinacolone retinoic acid ester, adding into the solution obtained in the step (1), and continuously stirring to completely dissolve the hydroxy pinacolone retinoic acid ester to obtain yellow transparent liquid;
and (3): cooling the yellow transparent liquid obtained in the step (2) to minus 10-minus 20 ℃ at a cooling speed of 4-6 ℃/hour, and then keeping the temperature for 24 hours;
and (4): heating the solution obtained in the step (3) to 40-80 ℃ at the heating rate of 4-6 ℃/h, and continuously stirring for 1 hour; in the step (3) and the step (4), the crystal form separated out through crystal form transformation is different from the initial original crystal form, so that the contact among molecules is further increased, and the particles are more uniform.
And (5): weighing 38-40% glycerol, preheating to 40-80 deg.C in water bath, slowly pouring into the solution obtained in step (4), and continuously stirring to obtain uniform liquid;
and (6): weighing 26-31% deionized water, preheating to 40-80 deg.C in water bath, slowly dripping into the system obtained in step (5), stirring for 10min, and cooling to 20-25 deg.C to obtain primary emulsion;
and (7): repeatedly freezing and thawing the primary emulsion obtained in the step (6) for 3 times at the temperature rising and falling speed of 5 ℃/hour within the range of-20 ℃ to 25 ℃; repeated freezing and thawing is beneficial to breaking the wall of a biological membrane when applied in the biological field, and in the step, the encapsulation rate of the hydroxy pinacolone retinoic acid ester can be improved through repeated freezing and thawing.
And (8): homogenizing the primary emulsion obtained in the step (7) by using a micro-jet homogenizer at the homogenizing pressure of 15000-30000psi for 1-5 times and the discharging temperature of 10-40 ℃ to obtain the uniform and transparent hydroxy pinacolone retinoic acid ester high-oil permeation promoting transfersome.
The beneficial effects of adopting the above technical scheme are:
through the proportion of the raw materials, the particles are more uniform through crystal form conversion and repeated freeze thawing, and the encapsulation efficiency of the hydroxy pinacolone retinoic acid ester is improved.
Preferably, the average particle size after homogenization is 20 to100 nm.
The invention also provides an application of the hydroxy pinacolone retinoic acid ester high-oil permeation-promoting carrier in skin cell anti-aging. It is generally applied to anti-wrinkle cosmetics, and is added at an addition temperature of 40 deg.C or below as a component of the cosmetics in the final preparation stage of the cosmetics.
The invention also provides a skin anti-wrinkle cosmetic which is characterized in that the hydroxy pinacolone retinoic acid ester high-oil penetration enhancer is added into the skin care cosmetic. Especially for essence, facial mask liquid and aqua.
Preferably, the content ratio of the hydroxy pinacolone retinoic acid ester high oil penetration enhancer is 1-15%, preferably 3-15%.
Preferably, 1-15 parts of hydroxy pinacolone retinoic acid ester high-oil modification transmission body and more than 2 parts of polyhydric alcohol are mixed and stirred uniformly in advance, then 20-30 parts of deionized water by weight are added for dilution, and finally the mixture is added into the anti-wrinkle cosmetic for skin.
Preferably, the polyol is glycerol.
Drawings
Fig. 1(a) is a subject dent volume image.
Fig. 1(b) is a wrinkle image of the subject.
Fig. 1(c) is a fine line image of the subject.
FIG. 2(a) is a graph showing the decrease of wrinkle index in subjects.
FIG. 2(b) is a graph showing the decrease of the fine streak index of the subjects.
Fig. 3 is a comparative graph of data for transdermal validation of comparative examples of the examples.
Detailed Description
The preferred embodiments in the following description are given by way of example only, and other obvious variations will occur to those skilled in the art. The basic principles of the invention, as defined in the following description, may be applied to other embodiments, variations, modifications, equivalents, and other technical solutions without departing from the spirit and scope of the invention.
The preparation of hydroxy pinacolone retinoic acid ester high oil penetration enhancer comprises the following steps:
(1) weighing the phosphatidylcholine, the polysorbate-80, the isononyl isononanoate, the ascorbyl palmitate and the tocopherol (vitamin E) according to the mass ratio, heating and stirring in a water bath at 60 ℃ to completely dissolve the phosphatidylcholine to obtain a uniform solution;
(2) weighing the hydroxy pinacolone retinoic acid ester according to the mass ratio, putting the weighed hydroxy pinacolone retinoic acid ester into the solution obtained in the step (1), and continuously stirring to completely dissolve the hydroxy pinacolone retinoic acid ester to obtain yellow transparent liquid;
(3) cooling the solution obtained in the step (2) to-20 ℃ at a cooling rate of 5 ℃/h, and then keeping the temperature for 24 hours;
(4) heating the solution obtained in the step (3) to 50 ℃ at the heating rate of 5 ℃/hour, and continuously stirring for 1 hour;
(5) weighing the glycerol according to the mass ratio, preheating the glycerol to 50 ℃ in a water bath, slowly pouring the glycerol into the solution obtained in the step (4), and continuously stirring to obtain uniform liquid;
(6) weighing deionized water according to the mass ratio, preheating the weighed deionized water in a water bath to 50 ℃, then slowly dripping the weighed deionized water into the system obtained in the step (5), continuously stirring the mixture for 10min, and cooling the mixture to 25 ℃ to obtain primary emulsion;
(7) repeatedly freezing and thawing the primary emulsion obtained in the step (6) for 3 times at the temperature rising and falling speed of 5 ℃/hour within the range of-20 ℃ to 25 ℃;
(8) homogenizing the primary emulsion obtained in the step (7) by using a micro-jet homogenizer, controlling the homogenizing pressure to be 15000-.
The detection shows that the average particle size of the hydroxy-pinacolone retinoic acid ester high oil penetration carrier is about 52nm, the zeta potential is-27 mv, and pdi is 0.176. Then, different cosmetic finished product formulas are prepared by using the hydroxy pinacolone retinoic acid ester high-oil penetration enhancer, and the specific formula is as follows:
example 1 an aqueous dispersion of this hydroxyppinacolone retinoic acid ester high oil penetration enhancer
The aqueous dispersion of the hydroxy pinacolone retinoic acid ester high-oil-permeability mediator described in example 1 was prepared at room temperature according to the ratio in the table, 2 parts of propylene glycol was dissolved in 93 parts of deionized water, and 5 parts of the hydroxy pinacolone retinoic acid ester high-oil-permeability mediator prepared according to the present invention was added to obtain a light yellow transparent aqueous dispersion.
Example 2 an essence prepared using the hydroxy pinacolone retinoic acid ester high oil penetration enhancer carrier
The essence of the hydroxy pinacolone retinoic acid ester high-oil-permeability-promoting carrier in example 2 is prepared at normal temperature according to the proportion in the table, the phase A component is taken and fully dissolved, the phase B component is added, the phase C component is added after the phase A component is completely dissolved, shearing homogenization is carried out for 2-3min at 3000-4000r/min, and then the phase D (5 parts of the hydroxy pinacolone retinoic acid ester high-oil-permeability-promoting carrier prepared by the method) is added and stirred uniformly, so that the light yellow semitransparent essence is obtained. "to 100" is to be interpreted as the final water replenishment to100 parts.
Example 3A serum prepared using the hydroxy pinacolone retinoic acid ester hyper-oleophilic transporter
The essential water of the hydroxy-pinacolone retinoic acid ester high-oil modification carrier described in example 3 is prepared at normal temperature according to the proportion in the table, the phase A component is taken and fully dissolved, and then the phase B component (5 parts of the hydroxy-pinacolone retinoic acid ester high-oil modification carrier prepared by the method is added with 2 parts of glycerol and uniformly stirred, and then 20 parts of deionized water) is added and uniformly stirred, so that light yellow transparent essential water is obtained. "to 100" is to be interpreted as the final water replenishment to100 parts.
The specific operation method of the in vitro skin permeation experiment comprises the following steps: in the experiment, pigskin is firstly placed in normal saline for unfreezing; cutting into 2.5cm × 2.5cm, placing between receiving pool and supply pool of Franz diffusion pool, and placing stratum corneum facing to supply pool; physiological saline solution is in the receiving pool; adding 0.02g of sample into a supply pool; the assembled Franz diffusion cell was placed in a transdermal diffusion apparatus and the experimental conditions were set as follows: the temperature was 37 ℃, the stirring speed was 600rpm and the skin penetration time was 24 h. And after the skin penetration is finished, taking out the pigskin from the diffusion pool, washing the skin with absolute ethyl alcohol for three times, then washing the skin with distilled water for three times, finally shearing the skin, placing the skin in a 2mL tissue extraction tube, carrying out ultrasonic treatment for 60min, filtering the supernatant with a 0.22 mu m organic filter membrane, and then measuring the content of HPR by adopting an HPLC method, namely the content of HPR in the skin.
Comparative example 1
Weighing the phase A components according to the proportion in the following table, uniformly mixing, stirring for 20min under the condition of water bath at 70 ℃ and 400rpm to completely dissolve solid components to obtain a uniform solution, then adding the phase B components in the corresponding proportion into the phase A, uniformly dissolving under the condition of continuous stirring, then adding the phase C components preheated to 70 ℃ into the AB mixed phase at one time, continuously stirring for 10min under the condition of water bath at 70 ℃ and 400rpm, then shearing for 5min under the condition of 10000rpm by using a high-speed shearing homogenizer to obtain yellow liquid, and cooling. The obtained sample is subjected to in vitro skin penetration test verification, and the retention rate of HPR in the skin layer is obtained.
Comparative example 2
Weighing the phase A components according to the proportion in the following table, uniformly mixing, stirring for 20min under the condition of water bath at 70 ℃ and 400rpm to completely dissolve solid components to obtain a uniform solution, then adding the phase B components in the corresponding proportion into the phase A, uniformly dissolving under the condition of continuous stirring, then adding the phase C components preheated to 70 ℃ into the AB mixed phase at one time, continuously stirring for 10min under the condition of water bath at 70 ℃ and 400rpm, then shearing for 5min under the condition of 10000rpm by using a high-speed shearing homogenizer to obtain yellow liquid, and cooling. The obtained sample is subjected to in vitro skin penetration test verification, and the retention rate of HPR in the skin layer is obtained.
Comparative example 3
Preparing a common nano composition according to the following components and proportions:
(1) weighing 1.2-pentanediol, 1.2-hexanediol, GTCC, isopropyl palmitate, coconut oil alcohol polyether-7 and polyglycerol-10 myristate according to the mass ratio, heating and stirring in a water bath at 50-80 ℃ to completely dissolve phosphatidylcholine to obtain a uniform solution;
(2) weighing the hydroxy pinacolone retinoic acid ester, the ascorbyl palmitate and the tocopherol (vitamin E) according to the mass ratio, then adding the weighed hydroxy pinacolone retinoic acid ester, ascorbyl palmitate and tocopherol into the solution obtained in the step (1), and continuously stirring to completely dissolve the hydroxy pinacolone retinoic acid ester, the ascorbyl palmitate and the tocopherol to obtain yellow transparent liquid;
(3) weighing deionized water according to the mass ratio, preheating the weighed deionized water to 50-80 ℃ in a water bath, then slowly dripping the weighed deionized water into the system obtained in the step (2), and continuously stirring the mixture for 10min to obtain primary emulsion;
(4) homogenizing the primary emulsion obtained in the step (3) by using a micro-jet homogenizer, controlling the homogenizing pressure to be 15000-30000psi, the cycle time to be 1-5 times, and the discharging temperature to be 20-50 ℃ to obtain the uniform and transparent hydroxy pinacolone retinoic acid ester composition.
The composition was found to have an average particle size of about 40nm, a zeta potential of-19 mv and a pdi of 0.123. The composition was then used to formulate a serum having the following formula:
the aqueous dispersion of the composition described in comparative example 3 was prepared at room temperature according to the formulation in the table, 2 parts of propylene glycol were dissolved in 93 parts of deionized water, and 5 parts of the nano-hydroxy pinacolone retinoic acid ester composition prepared in comparative example 3 was added to obtain a light yellow transparent aqueous dispersion. The obtained sample is subjected to in vitro skin penetration test verification, and the retention rate of HPR in the skin layer is obtained.
The skin care formulations of examples 1-3 and comparative examples 1-3 were also verified transdermally and the results are shown in fig. 3.
It can be seen that when the high oil penetration enhancer of hydroxy pinacolone retinoic acid ester prepared by the invention is applied to a proper cosmetic formula, the retention amount of hydroxy pinacolone retinoic acid ester in skin can be remarkably increased, the retention multiple is more than 8 times of that of comparative example 1, and the anti-wrinkle effect of the product can be remarkably increased.
Efficacy evaluation tests were carried out according to the method specified in the group standard "cosmetic anti-wrinkle efficacy test method" T/ZHCA006-2019 ". 32 qualified test volunteers were screened according to the requirements of the subjects specified in the above group standards.
The tested part is the external canthus, and before each test, the tested part is cleaned uniformly by the tested person, and is sucked dry by a chipless paper towel, and the tested person sits still for 20min in a standard test environment and cannot drink water and beverage. The subjects had relaxed eyes when tested. The test sample formulation is shown in table 3. Volunteers took soybean grain sized test samples every morning and evening and smeared on the external canthus. The measurement time points were 0 day before use and 14 days and 28 days after use of the product. The test results were evaluated as comparative data between 0 days before use and 14 and 28 days after use. The test environment is as follows: temperature 20-22 ℃, humidity: 40 to 60 percent. The test conditions during the test were kept consistent. .
The subject partial image acquisitions are shown in fig. 1, where fig. 1(a) W0, W14, W28 are dimple volume images acquired using 0 day, 14 day, 28 day, respectively, fig. 1(b) W0, W14, W28 are wrinkle images acquired using 0 day, 14 day, 28 day, respectively, and fig. 1(c) W0, W14, W28 are fine line images acquired using 0 day, 14 day, 28 day, respectively.
It is evident from the topical skin pattern of the subject that there was a significant reduction in canthus wrinkles in the subject after two weeks using the sample containing the hydroxyppinacolone retinoic acid ester hyperosmotic mediator. Referring to fig. 2(a) and 2(b), it can be seen from the graphs showing the decrease of the wrinkle and fine line indexes of the subjects that the average length, width and depth of the wrinkles and fine lines of the subjects showed a decrease in various degrees after 2 weeks and 4 weeks using the samples containing hydroxyppinacolone retinoic acid ester hyperosmotic carriers, and all indexes showed a decrease. The reason why the anti-wrinkle and wrinkle-reducing effects are obvious is that the penetration ability is increased after the hydroxy pinacolone retinoic acid ester is treated, the onset time is greatly reduced, and the anti-wrinkle effect of the product can be obviously increased.
It will be appreciated by persons skilled in the art that the embodiments of the invention shown in the foregoing description are by way of example only and are not limiting of the invention. The objects of the invention have been fully and effectively accomplished. The functional and structural principles of the present invention have been shown and described in the examples, and any variations or modifications of the embodiments of the present invention may be made without departing from the principles.
Claims (9)
1. The hydroxy pinacolone retinoic acid ester high-oil permeation-promoting carrier is characterized by comprising the following components in percentage by mass: 38-40% of glycerin, 26-31% of water, 19-21% of isononyl isononanoate, 3-6% of phosphatidylcholine, 804-7% of polysorbate, 1.9-2.1% of hydroxyppinacolone retinoic acid ester, 0.0004-0.012% of ascorbyl palmitate and 0.0004-0.012% of tocopherol.
2. The hydroxyppinalone retinoic acid ester high-oil permeability mediator according to claim 1, wherein the ratio of the components of the ascorbyl palmitate and the tocopherol is: 1: 1-1: 3.
3. a method for preparing hydroxy pinacolone retinoic acid ester high oil permeability-promoting transfersome is characterized by comprising the following steps:
step (1): weighing isononyl isononanoate 19-21%, phosphatidylcholine 3-6%, polysorbate-80 4-7%, ascorbyl palmitate 0.0004-0.012%, and tocopherol, and heating and stirring in water bath at 50-80 deg.C to completely dissolve phosphatidylcholine to obtain uniform solution;
step (2): weighing 1.9-2.1% of hydroxy pinacolone retinoic acid ester, adding into the solution obtained in the step (1), and continuously stirring to completely dissolve the hydroxy pinacolone retinoic acid ester to obtain yellow transparent liquid;
and (3): cooling the yellow transparent liquid obtained in the step (2) to minus 10-minus 20 ℃ at a cooling rate of 4-6 ℃/hour, and then keeping for 24 hours;
and (4): heating the solution obtained in the step (3) to 40-80 ℃ at the heating rate of 4-6 ℃/h, and continuously stirring for 1 hour;
and (5): weighing 38-40% glycerol, preheating to 40-80 deg.C in water bath, slowly pouring into the solution obtained in step (4), and continuously stirring to obtain uniform liquid;
and (6): weighing 26-31% deionized water, preheating to 40-80 deg.C in water bath, slowly dripping into the system obtained in step (5), stirring for 10min, and cooling to 20-25 deg.C to obtain primary emulsion;
and (7): repeatedly freezing and thawing the primary emulsion obtained in the step (6) for 3 times at the temperature rising and falling speed of 5 ℃/hour within the range of-20 ℃ to 25 ℃;
and (8): homogenizing the primary emulsion obtained in the step (7) by using a micro-jet homogenizer, controlling the homogenizing pressure to be 15000-.
4. The hydroxyppinacolone retinoic acid ester high oil permeability mediator according to claim 3, wherein the average particle size after homogenization is 20-100 nm.
5. Use of the hydroxyppinacolone retinoic acid ester high-oil-permeability transporter according to any one of claims 1 to 4 for skin cell anti-aging.
6. An anti-wrinkle cosmetic for skin, comprising the hydroxyppinacolone retinoic acid ester high-oil penetration enhancer according to any one of claims 1 to 4.
7. The hydroxyppinacolone retinoic acid ester high-oil permeability mediator according to claim 6, wherein the content ratio of the hydroxyppinacolone retinoic acid ester high-oil permeability mediator is 1-15%, preferably 3-15%.
8. The hydroxy pinacolone retinoic acid ester high-oil penetration enhancer of claim 7, wherein 1-15 parts of hydroxy pinacolone retinoic acid ester high-oil modification enhancer and more than 2 parts of polyhydric alcohol are mixed and stirred uniformly in advance, and then 20-30 parts by weight of deionized water is added for dilution, and finally the mixture is added into the anti-wrinkle cosmetics for skin.
9. The hydroxyppinacolone retinoic acid ester high oil permeability transporter according to claim 8, wherein the polyol is glycerol.
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| CN115089507A (en) * | 2022-07-05 | 2022-09-23 | 欧诗漫生物股份有限公司 | Hydroxy pinacolone retinoic acid ester solution, preparation method thereof and skin external preparation |
| CN115554175A (en) * | 2022-09-14 | 2023-01-03 | 纳爱斯浙江科技有限公司 | Supermolecule nano emulsion based on tocopherol and derivatives thereof, and preparation method and application thereof |
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| CN108324699A (en) * | 2017-01-20 | 2018-07-27 | 浙江医药股份有限公司新昌制药厂 | Stable fat-soluble active ingredient composition, micro-capsule and its preparation method and application |
| CN110623858A (en) * | 2019-08-28 | 2019-12-31 | 上海克琴科技有限公司 | Preparation method and application of vitamin A nano inclusion |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108324699A (en) * | 2017-01-20 | 2018-07-27 | 浙江医药股份有限公司新昌制药厂 | Stable fat-soluble active ingredient composition, micro-capsule and its preparation method and application |
| CN110623858A (en) * | 2019-08-28 | 2019-12-31 | 上海克琴科技有限公司 | Preparation method and application of vitamin A nano inclusion |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN115089507A (en) * | 2022-07-05 | 2022-09-23 | 欧诗漫生物股份有限公司 | Hydroxy pinacolone retinoic acid ester solution, preparation method thereof and skin external preparation |
| CN115554175A (en) * | 2022-09-14 | 2023-01-03 | 纳爱斯浙江科技有限公司 | Supermolecule nano emulsion based on tocopherol and derivatives thereof, and preparation method and application thereof |
| CN115554175B (en) * | 2022-09-14 | 2024-04-23 | 纳爱斯浙江科技有限公司 | Supermolecule nanoemulsion based on tocopherol and derivatives thereof, and preparation method and application thereof |
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