WO2022099970A1 - 一种低氧诱导靶向抗衰修护方法 - Google Patents
一种低氧诱导靶向抗衰修护方法 Download PDFInfo
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- hypoxia
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- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Images
Classifications
-
- 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
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
-
- 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
- A61K8/35—Ketones, e.g. benzophenone
- A61K8/355—Quinones
-
- 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
-
- 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
- A61K8/678—Tocopherol, i.e. vitamin E
-
- 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
- A61K8/68—Sphingolipids, e.g. ceramides, cerebrosides, gangliosides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/59—Mixtures
- A61K2800/592—Mixtures of compounds complementing their respective functions
Definitions
- the present invention relates to the technical field related to skin repair, and more particularly, the present invention provides a hypoxia-induced targeted anti-aging repair method.
- Aging represents all the physiological changes in the body that occur over time, and the state and speed of aging varies from individual to individual and is affected by a variety of causes. Even within an individual, aging manifests differently for each organ, so individual-oriented aging studies have limitations. As the first and most easily detected aging process in the human body, skin aging is the comprehensive result and external manifestation of the overall function beginning to age.
- Skin aging reduces the skin's ability to protect and regulate the body.
- the skin cannot adapt to changes in the internal and external environment, and changes in overall appearance such as color, lustre, shape, texture, etc., will lead to fine wrinkles, decreased elasticity, and loose skin. , Rough, yellowish or grayish-yellow skin discoloration, telangiectasia, formation of pigmented spots, etc.
- Three major skin changes can induce the above aging phenomena: thinning of the epidermis leads to skin sensitivity and hyperpigmentation; thinning of the dermis leads to increased fine lines and dark lines and decreased skin elasticity; cell dehydration leads to dry and rough skin.
- the present invention realizes the targeted and precise delivery of substances and energy, as well as the precise induction and activation of damaged and aging skin cells in a hypoxic environment, and uses functional factors to synergize with it. In this process, it can effectively affect cell growth, proliferation, differentiation and damage repair, protect cells from free radical damage, inhibit lipid It can also improve the microcirculation of the skin, promote the metabolism of the skin, better promote the production of collagen, and solve the problem of skin aging.
- a first aspect of the present invention provides a hypoxia-induced targeted anti-aging repair method, including the processes of channel recognition (Channel), vesicle transport (Transport), induced activation (Activation) and damage repair (Repair).
- Channel channel recognition
- Transport vesicle transport
- Activation induced activation
- Repair damage repair
- Transmembrane transport can communicate the connections between inside and outside cells and between various organelles in cells, ensure the normal exchange of substances in life activities such as metabolism, and is also the basis of biofilm energy conversion and information transmission. It is divided into two categories, one is the transmembrane transport of small molecules and ionic substances, including active transport and passive transport, and the other is the membrane vesicle transport of macromolecules and granular substances, including endocytosis and exocytosis.
- the "channel recognition" described in the present invention includes the transmembrane transport of small molecular substances, and according to the type of substances transported across the membrane, the channel recognition includes small molecular channel recognition; wherein the small molecules such as water molecules, small molecules of collagen etc.; and moisture is very important for the skin, and the lack of human skin moisture will inevitably cause problems such as skin dryness and aging; preferably, in the present invention, the water molecule channel is studied.
- the present invention utilizes a natural moisturizing factor to increase the recognition and transport of water on the skin surface by skin cell aquaporins
- the moisturizing factor is a substance well known in the art, such as selected from hyaluronic acid, collagen, vitamins, hyaluronic acid, cholesterol, fatty acids, phospholipids , linoleic acid, glycosaminoglycan, glycerin, amino acids, polyamino acids, amino acid surfactants, pyrrolidone carboxylic acid and its salts, N-acetylglucosamine, animal and plant polysaccharides, coenzyme Q10, rice flour, white Gelatin, oligosaccharides, monosaccharides, saponins, vegetable peptides, phospholipids, sericin, albumin, chondroitin, ceramides, collagen, chitin and chitosan, etc.
- amino acids for example, aspartic acid, threonine, serine, glutamic acid, citrulline, proline, glycine, alanine, cysteine, valine, methionine, isoleucine acid, leucine, tyrosine, phenylalanine, tryptophan, lysine, ornithine, histidine, arginine, etc.
- animal and plant polysaccharides (1) as plant polysaccharides, for example, guar gum, locust bean gum, quince seed gum which are seed polysaccharides, carrageenan which is seaweed polysaccharide, alginic acid , are resin polysaccharides of arabic rubber, tragacanth, etc.; (2) as animal polysaccharides, such as collagen peptides extracted from fish intestines and fish scales.
- saponins for example, tea, licorice, ginseng, bamboo ginseng, soybean, Bupleurum, horse chestnut, loofah, Polygala, bellflower, Polygala, Ophiopogon, Mutong, thyme, Achyranthes, Substances derived from plants contained in smilax smilax and the like.
- the present invention preferably uses hyaluronic acid as a moisturizing factor; in order to further promote skin metabolism, cell hydration and skin elasticity, the hyaluronic acid selected in the present invention includes high molecular weight hyaluronic acid, medium molecular weight hyaluronic acid, and hyaluronic acid.
- hyaluronic acid and low molecular weight hyaluronic acid the synergistic effect of three different types of hyaluronic acid can promote the synthesis of collagen and ceramide, as well as the migration and proliferation of skin cells, and can also lock moisture, replenish moisture and The effect of nourishing the stratum corneum can also regulate the activity of immune cells.
- the "high molecular weight hyaluronic acid” in the present invention refers to sodium hyaluronate; the "medium molecular weight hyaluronic acid” refers to hydroxypropyltrimethylammonium chloride hyaluronic acid; the “Low molecular weight hyaluronic acid” refers to hydrolyzed hyaluronic acid.
- hydrolyzed hyaluronic acid, hydroxypropyl trimethyl ammonium chloride hyaluronic acid as low-molecular and medium-molecular hyaluronic acid and macromolecular hyaluronic acid, such as sodium hyaluronate can synergize, both to meet the requirements of low and medium molecular weight hyaluronic acid.
- Molecular or medium molecular hyaluronic acid is absorbed by cells, thereby promoting the synthesis of collagen and ceramide, as well as the migration and proliferation of skin cells; at the same time, it also has the effect of locking moisture on the skin surface, replenishing moisture, and nourishing the stratum corneum.
- the weight ratio of low molecular weight hyaluronic acid, ultra-low molecular weight hyaluronic acid and high molecular weight hyaluronic acid is (0.5-1.5):(0.5-1.5):(0.5-1.5).
- the present invention does not specifically limit the sources of sodium hyaluronate, hydrolyzed hyaluronic acid, and hydroxypropyltrimethylammonium chloride hyaluronic acid.
- sodium hyaluronate is purchased from QPCorporation, HYALURONSAN HA-LQH ;
- Hydrolyzed hyaluronic acid was purchased from QPCorporation, Hydroxypropyltrimethylammonium chloride hyaluronic acid was purchased from QPCorporation,
- the synergistic effect of different transmembrane transport modes is adopted, that is, the system of the present invention also includes a transmembrane transport mode in the form of "vesicle transport" to realize the membrane vesicle transport of macromolecules and particulate matter, using vesicles
- the transport works synergistically with the water molecule channel to achieve the transport of substances across the barrier.
- macromolecular substances and particulate substances cannot pass through the cell membrane, so they need to be transported by membrane vesicles, that is, the substances are encapsulated by the membrane, form vesicles, fuse with the membrane or break during the transport process in and out of the cell.
- the fatty acid outer tail of the cell membrane has a certain degree of hydrophobicity, and the substances with high lipid solubility are easily diffused and absorbed, while the lipid solubility is low. Or non-fat-soluble substances are more difficult to pass through, and it is more difficult to fuse with the cell membrane, so that some nutrients cannot be absorbed by skin cells, thus affecting the absorption effect of skin care products when they are used.
- the present invention is based on the consideration of the above problems, preferably, in the process of membrane vesicle transport, the vesicle transport method is preferentially adopted, and in the process of vesicle transport, the vesicle-mimetic component is used to wrap the effective components carried by the vesicle to form nano-lipid vesicles.
- the vesicle-mimetic components include but are not limited to lecithin, and its components include phosphoric acid, choline, fatty acids, glycerol, glycolipids, triglycerides and phospholipids.
- nano-lipocapsules can carry various macromolecules or small molecules of nutrients for skin repair.
- the present invention is based on the consideration of skin anti-aging and skin repair effects.
- the active ingredients carried by the pellets include functional factors and water molecules; further, the functional factors include any one or a combination of a cell activity promoting factor, a tissue repair factor, a hypoxia-inducible regulator, and an antioxidant factor.
- vesicle transport can synergize with transmembrane transport in the form of water channel recognition.
- water molecule channels are more efficiently opened to achieve water replenishment.
- the efficient transport of functional factors across the barrier can avoid stress and damage to the skin barrier, and can promote and repair the skin barrier function to a certain extent.
- hypoxia-inducible regulator indirectly activates the cell activity through hypoxia-inducing substances, which can avoid the increase of the content of reactive oxygen species and free radicals in the cell, and also avoid the DNA Structural damage and decreased protease activity.
- hypoxia-inducible regulators are used to mediate the fusion of liposome globules with the target cell membrane under hypoxia-inducible signals, and release functional factors and water molecules.
- hypoxia-inducible regulators can activate damaged and senescent cells to ensure effective targeted repair.
- hypoxia-inducible regulators Under the action of hypoxia-inducible regulators, they can synergize with nano-lipocapsules to achieve the targeted and precise release of functional factors is because in damaged and aging skin, cell respiration is poor, and damaged and aging skin cells have insufficient vitality and are in a hypoxic state, which can trigger hypoxic signals and induce the production of hypoxia-inducible factors.
- hypoxia-inducible regulators can be quickly captured by hypoxia-inducible regulators, thereby regulating HIF-1 and participating in the respiratory chain process of skin cells to achieve targeted delivery and precise release of vesicles , and then use the functional factors encapsulated by it to improve the efficient utilization of nutrients; to achieve rapid, accurate and efficient repair of damaged and senescent cells;
- the hypoxia-inducing regulator is a substance that can sense hypoxia signals and regulate cellular respiration ;
- the present invention adopts the synergistic effect of cell activity promoting factor and liposome globules to promote high-efficiency fusion, which can effectively promote the activity of fibroblasts, activate the production of dermal collagen, and also It participates in the composition of red blood cells, and works synergistically with iron to promote the formation of tissues and mucous membranes, thereby achieving efficient fusion with the target cell membrane.
- Cell activity promoting factors can be components well known in the art, such as retinol and its derivatives, retinol is a fat-soluble fat-soluble vitamin, resistant to high temperature, and retinol derivatives are actively metabolized in the body
- retinoic acid mediates the expression of two major types of retinoic acid receptors RARs ( ⁇ , ⁇ , ⁇ ) and RXRs ( ⁇ , ⁇ , ⁇ ) to regulate gene expression, forming structural proteins, enzymes and extracellular matrix of the skin, etc.
- Flavanol derivatives such as retinyl palmitate.
- the signal molecules of the stress pathway activate protein kinases and transcription factors to conduct intracellular signal transduction, and further, the carrier substance of the nano-lipocapsules achieves targeted repair of cells; in order to further achieve the skin repair effect, preferably, oxidation
- the signaling molecules of the stress pathway include tissue repair factors; tissue repair factors can be components well known in the art, selected from one or several combinations of growth factors, extracts, and ceramides; as growth factors, such as epidermal growth factor , fibroblast growth factor, vascular endothelial growth factor, etc.; as extracts include plant extracts, animal extracts, microbial extracts, such as snow algae extract, anchovy extract, pigeon bean leaf extract, large wing thistle Genus Extract, Boswellia Extract, Ginkgo Biloba Extract, Pigeon
- the tissue repair factor includes ceramide; further preferably, the ceramide is selected from any one or more of ceramide 3, ceramide 4, ceramide 6II, ceramide 1, ceramide 1A, and ceramide 2 more preferably, the ceramides are ceramide 3, ceramide 6II and ceramide 2; further preferably, the mass ratio of ceramide 3, ceramide 6II and ceramide 2 is (0.8 ⁇ 1.2): (0.8 ⁇ 1.2): (0.8-1.2); further preferably, the mass ratio of ceramide 3, ceramide 6II and ceramide 2 is 1:1:1.
- the applicant found that when ceramides participate in the damage repair process as a tissue repair factor, it can effectively fit the skin and increase the thickness and elasticity of the stratum corneum, thereby better achieving damage resistance and repair effects.
- the applicant found that when the antioxidant factor is used synergistically with other functional factors in the present invention, the effect of skin repair and anti-aging can be better achieved.
- Tocopherol can effectively reduce the generation of free radicals, and at the same time, it can form a stable state with free radicals or reactive oxygen species to avoid free radicals.
- the damage of radicals or reactive oxygen species to cells is also conducive to enhancing the activity of cell telomerase and promoting cell repair.
- Antioxidant factors can be components well known in the art, substances with anti-oxidative free radical effect, selected from one of plant extracts, animal extracts, microbial extracts, vitamins, peptide substances, phenolic substances, enzymes or a combination of several; as plant extracts such as Alisma orientalis extract, sea buckthorn leaf extract, angelica extract, Ligustrum lucidum extract, Prunella vulgaris extract, Scutellaria chinensis root extract, Schisandra chinensis extract, licorice root extract , salvia root extract, hibiscus flower extract, marigold flower extract, etc.; as animal extract, such as American cockroach extract, etc.; as microbial extract, such as lactic acid bacteria extract, etc.; as vitamin substances, such as vitamin A , vitamin C, vitamin D, vitamin E, etc.; as antioxidant factors are peptide substances, such as rice bran peptide, reduced glutathione, soybean peptide, milk protein peptide, etc.; as phenolic substances, such
- the present invention utilizes four processes of channel identification (Channel), vesicle transport (Transport), induced activation (Activation) and damage repair (Repair) to cooperate with each other, and uses channel identification to repair and improve the basal metabolic environment, while in vesicle transport
- the vesicle-level nano-liposome globules that carry functional factors and water molecules are used, which is more conducive to cross-barrier transport, and the key functional factors carried by them work synergistically with them to achieve precise activation of damaged and aging cells.
- the key functional factors carried by them work synergistically with them to achieve precise activation of damaged and aging cells.
- it strengthens the communication ability between cells and reduces the damage of free radicals.
- various functional factors coordinate with each other to achieve the effect of repairing skin cells and anti-aging.
- a second aspect of the present invention provides a skin care composition formed by the hypoxia-induced targeted anti-aging repair method.
- the composition can be prepared in any dosage form commonly prepared in the art. For example, solutions, suspensions, lotions, creams, gels, creams, moisturizers, powders, soaps, facial cleansers containing surfactants, oils, powder foundations, lotion foundations, wax foundations and sprays, etc., but not limited to this. More specifically, it can be prepared into toner, nutritional lotion, nutritional cream, massage cream, essence, eye cream, facial cleanser, facial cleanser, facial mask, spray, powder, dry powder, lip balm, stick lipstick, eye shadow, wash Forms such as hair lotion and conditioner.
- oil-in-water O/W
- water-in-oil Water-in-Oil, W/O
- water-in-silicone Water-in-Silicone, W/ S
- Oil-in-Water-in-Oil O/W/O
- Water-in-Oil-in-Water W/O/W
- the skin care composition is based on weight percentage, and the raw materials of the skin care composition include 20-80 wt% moisturizing factor, 0.1-10 wt% cell activity promoting factor, 0.01-5 wt% hypoxia-inducing regulator, 0.01-20 wt% antioxidant Oxidation factor, 0.1-20wt% tissue repair factor and balance water.
- a third aspect of the present invention provides a skin care product containing the skin care composition, and the product also includes any dosage form.
- any dosage form for example, solutions, suspensions, lotions, creams, gels, creams, moisturizers, powders, soaps, facial cleansers containing surfactants, oils, powder foundations, lotion foundations, wax foundations and sprays, etc., but not limited to this. More specifically, it can be prepared into toner, nutritional lotion, nutritional cream, massage cream, essence, eye cream, facial cleanser, facial cleanser, facial mask, spray, powder, dry powder, lip balm, stick lipstick, eye shadow, wash Forms such as hair lotion and conditioner.
- oil-in-water O/W
- water-in-oil Water-in-Oil, W/O
- water-in-silicone Water-in-Silicone, W/ S
- Oil-in-Water-in-Oil O/W/O
- Water-in-Oil-in-Water W/O/W
- Fig. 1 the moisturizing efficacy test result of embodiment 1 skin care combination
- Figure 2 Schematic diagram of the wrinkle evaluation level
- Figure 3 The test results of the lightening effect of the skin care combination of Example 1 on wrinkles.
- This embodiment provides a hypoxia-induced targeted anti-aging repair method, including the processes of channel recognition (Channel), vesicle transport (Transport), induced activation (Activation), and damage repair (Repair).
- Channel channel recognition
- Transport vesicle transport
- Activation induced activation
- Repair damage repair
- the natural moisturizing factor is hyaluronic acid; hyaluronic acid includes high molecular weight hyaluronic acid, medium molecular weight hyaluronic acid and low molecular weight hyaluronic acid; high molecular weight hyaluronic acid, medium molecular weight hyaluronic acid and low molecular weight hyaluronic acid
- the mass ratio of hyaluronic acid is 1:1:1;
- the "high molecular weight hyaluronic acid” refers to sodium hyaluronate; the “medium molecular weight hyaluronic acid” refers to hydroxypropyltrimethylammonium chloride hyaluronic acid; the “low molecular weight hyaluronic acid””Acid” refers to hydrolyzed hyaluronic acid; sodium hyaluronate was purchased from QPCorporation, HYALURONSAN HA-LQH; hydrolyzed hyaluronic acid was purchased from QPCorporation, Hydroxypropyltrimethylammonium chloride hyaluronic acid was purchased from QPCorporation,
- vesicle-mimetic components are used to encapsulate the active ingredients carried by them to form nano-liposome globules; the active ingredients carried by the nano-liposome globules include functional factors and water molecules; and cell activity promoting factors are used. It works synergistically with liposomes to promote high-efficiency fusion.
- Functional factors include cell activity promoting factor, tissue repair factor, hypoxia-inducible regulator, and antioxidant factor; cell activity-promoting factor is retinyl palmitate; hypoxia-inducible regulator is ubiquinone; antioxidant factor is tocopherol; The tissue repair factor is ceramide.
- hypoxia-inducible regulator indirectly activates cell activity through hypoxia-inducible substances, which can avoid the increase of intracellular reactive oxygen species and free radicals, as well as DNA structural damage and reduction of protease activity.
- Hypoxia-inducible regulators mediate the fusion of liposomes and target cell membranes under hypoxia-inducible signals, and release functional factors and water molecules; nano-liposomes carry substances to achieve targeted repair of cells.
- the signaling molecules of the oxidative stress pathway activate protein kinases and transcription factors for intracellular signaling, and ceramide acts as a tissue repair factor.
- the four processes of channel recognition (Channel), vesicle transport (Transport), induced activation (Activation) and damage repair (Repair) cooperate with each other, and use channel recognition to repair and improve the basal metabolic environment.
- vesicle transport the use of vesicle-level nano-liposome globules that carry functional factors and water molecules is more conducive to trans-barrier transport, and the key functional factors carried by the vesicles work synergistically with them to achieve the goal of treating damaged and senescent cells. Under the action of cell activity promoting factors, it can strengthen the communication ability between cells and reduce the damage of free radicals.
- various functional factors coordinate with each other to achieve the effect of repairing skin cells and anti-aging.
- This embodiment also provides a skin care composition formed by using the hypoxia-induced targeted anti-aging repair method, in terms of weight percentage, comprising 45wt% moisturizing factor, 1.5wt% cell activity promoting factor, 0.5wt% low Oxygen-inducible regulatory factor, 0.8wt% antioxidant factor, 1.1wt% tissue repair factor and balance water;
- the moisturizing factor is hyaluronic acid
- hyaluronic acid includes high molecular weight hyaluronic acid, medium molecular weight hyaluronic acid and low molecular weight hyaluronic acid
- high molecular weight hyaluronic acid, medium molecular weight hyaluronic acid and low molecular weight hyaluronic acid The mass ratio of hyaluronic acid is 1:1:1;
- the "high molecular weight hyaluronic acid” refers to sodium hyaluronate; the “medium molecular weight hyaluronic acid” refers to hydroxypropyltrimethylammonium chloride hyaluronic acid; the “low molecular weight hyaluronic acid””Acid” refers to hydrolyzed hyaluronic acid; sodium hyaluronate was purchased from QPCorporation, HYALURONSAN HA-LQH; hydrolyzed hyaluronic acid was purchased from QPCorporation, Hydroxypropyltrimethylammonium chloride hyaluronic acid was purchased from QPCorporation,
- Cell activity promoting factor is retinyl palmitate; hypoxia-inducible regulator is ubiquinone; antioxidant factor is tocopherol; tissue repair factor is ceramide 3, ceramide 6II and ceramide 2; ceramide 3, ceramide The mass ratio of 6II and ceramide 2 is 1:1:1.
- the above skin care composition can be sprayed on the skin surface for absorption.
- Detection method Use Corneometer CM825, a skin moisture tester, to measure the cheek area 3 times and obtain the average value.
- Detection environment temperature 20.1 °C ⁇ 21.2 °C, relative humidity 48.1% ⁇ 53.2%.
- the statistical method is:
- Statistical analysis software was SPSS. The measured values at different time points are compared with the basic value, and before and after use. If the value is normally distributed, the t-test method is used for statistical analysis; if the value is not normally distributed, the rank-sum test method is used for statistical analysis;
- test level 0.05.
- the safety evaluation adopts the method of statistical description, and analyzes the degree of adverse events and the duration of adverse events on a case-by-case basis.
- the rate of change is the rate of change relative to before use, and the calculation formula is as follows:
- T 0 the basic value of skin parameters before using the product in the test area.
- T 1 the skin parameter value in the first hour after using the product in the test area.
- T 4 the skin parameter value at the 4th hour after using the product in the test area.
- T 8 the skin parameter value on the 8th hour after using the product in the test area.
- N the number of subjects.
- Subject 35 subjects were enrolled, and 35 subjects were finally counted, and the product used was the skin care composition obtained in Example 1.
- the moisture content of the skin stratum corneum in the blank control area at 1 hour was not significantly different from the baseline value (p>0.05), and the decrease rate at 1 hour was 0.07%. There was a significant decrease (0.01 ⁇ p ⁇ 0.05) compared with the basal value, and the decrease rate at 4 hours was 0.9%.
- the moisture content of the skin stratum corneum in the blank control area at 8 hours was significantly decreased compared with the basic value (p ⁇ 0.01), the 8-hour drop was 1.96%.
- the skin care composition formed by the method for targeted anti-aging and repairing provided by the present invention has good moisturizing properties to the skin and can effectively maintain the moisture on the skin surface.
- Detection method Use the skin fast optical imaging system PRIMOS lite to measure the canthus area for 3 times, and calculate the average value.
- Detection environment temperature 20.1 °C ⁇ 21.2 °C, relative humidity 48.1% ⁇ 53.2%.
- the statistical method is:
- Statistical analysis software was SPSS. The measured values at different time points are compared with the basic value, and before and after use. If the value is normally distributed, the t-test method is used for statistical analysis; if the value is not normally distributed, the rank-sum test method is used for statistical analysis;
- test level 0.05.
- the safety evaluation adopts the method of statistical description, and analyzes the degree of adverse events and the duration of adverse events on a case-by-case basis.
- the rate of change is the rate of change relative to before use, and the calculation formula is as follows:
- D0 the basic value of skin parameters before using the product in the test area.
- D14 The test area used the product for 2 weeks, and the skin parameter value.
- D28 The test area used the product for 4 weeks, and the skin parameter value.
- N the number of subjects.
- the skin care composition formed by the method for targeted anti-aging and repairing provided by the present invention has a good effect of lightening wrinkles on the skin.
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Abstract
本发明的第一方面提供了一种低氧诱导靶向抗衰修护方法，包括通道识别(Channel)、囊泡转运(Transport)、诱导激活(Activation)以及损伤修复(Repair)的过程。在皮肤抗衰老以及修护过程中，实现物质与能量的靶向送达，以及对损伤和衰老皮肤细胞的精准诱导与激活，从而实现有效组分的高效利用，保护细胞免受自由基的伤害，更好促进胶原蛋白的产生，解决皮肤衰老问题。
Description
本发明涉及皮肤修复相关的技术领域，更具体地，本发明提供一种低氧诱导靶向抗衰修护方法。
衰老表示随着时间流逝而出现的身体的所有生理变化，而衰老状况和速度因个体情况而不同，并且受到多种原因的影响。即使在一个个体中，衰老对于每个器官也表现出不同的状况，因此面向个体的衰老研究具有局限性。皮肤的衰老作为人体最先和最容易被察觉的衰老过程，是整体机能开始走向老化的综合结果和外部体现。
皮肤衰老使得皮肤对机体的防护能力、调节能力等减退，由此皮肤不能适应内外环境的变化，出现颜色、色泽、形态、质感等外观整体状况的改变，会出现细小皱纹、弹性下降、皮肤松弛、粗糙、淡黄或灰黄色的皮肤变色、毛细血管扩张、色素斑形成等。三大皮肤改变可诱使以上衰老现象的产生：表皮变薄导致皮肤敏感和色素沉着；真皮变薄导致细纹暗纹增多和皮肤弹性下降；细胞失水导致皮肤干燥粗糙。
而皮肤细胞的物质和能量供应不足，致使皮肤损伤无法被及时修复，是造成皮肤衰老的主要原因，当细胞生长和修复所需的各种养分、生长因子和氧气供应不足时，皮肤自我修复和新生的能力会逐渐减弱，皮肤就会失去活力，目前皮肤修护的相关研究中，大部分会采用各种营护肤组分实现对皮肤的修护，但是实际使用过程中，由于较难保证营养护肤组分的运输有效性以及其对靶向细胞的修复、传递精准性，导致皮肤对护肤组分的有效成分的利用率低，不能很好地对损伤和衰老皮肤细胞进行有效修复与保护。
发明内容
本发明为解决上述问题，即皮肤抗衰老以及修护过程中，实现物质与能量的靶向精准送达，以及对低氧环境下损伤和衰老皮肤细胞的精准诱导激活，利用功能因子与之协同作用，实现对损伤、衰老细胞的高效、精准修复，实现有效组分的高效利用，在该过程中能有效影响细胞生长、增殖、分化以及损伤修复，保护细胞免受自由基的伤害，抑制脂质过氧化、保护生物膜结构的完整性和皮肤脂质 屏障的完整性；也能够改善皮肤微循环，促进皮肤的新陈代谢，更好促进胶原蛋白的产生，解决皮肤衰老问题。
本发明的第一方面提供了一种低氧诱导靶向抗衰修护方法，包括通道识别(Channel)、囊泡转运(Transport)、诱导激活(Activation)以及损伤修复(Repair)的过程。
在皮肤保养以及修护过程中所需要的物质，例如水分、生长因子、氧气等，进入人体被吸收从而发挥其应有的功能是需要多种形式的跨膜运输协同来实现的。跨膜运输可以沟通细胞内外及细胞内各细胞器之间的联系，保证新陈代谢等生命活动中的正常物质交换，也是生物膜能量转换和信息传递等功能的基础；而物质跨膜运输的方式可分为两大类，一类是小分子和离子物质的跨膜运输，包括主动运输和被动运输，另一类是大分子和颗粒物质的膜泡运输，包括胞吞作用和胞吐作用。
在本发明中所述的“通道识别”包括小分子物质的跨膜运输，根据跨膜运输的物质种类，通道识别包括小分子通道识别；其中所述的小分子例如水分子、小分子胶原蛋白等；而水分对于皮肤来说是至关重要的，人体皮肤水分的缺失会不可避免地引起皮肤干瘪、衰老等问题；优选地，本发明中针对水分子通道进行了研究，通道识别过程中，利用天然保湿因子促进水分子通道的开放，调节基础代谢，提高了皮肤对水分的吸收能力，同时调节了细胞的基础代谢环境，可以促进后源营养物质的进入。
本发明利用天然保湿因子增加皮肤细胞水通道蛋白对皮肤表面水分的识别与运输，保湿因子为本领域熟知的物质，例如选自透明质酸、胶原蛋白、维生素、玻尿酸、胆固醇、脂肪酸、磷脂质、亚麻油酸、葡萄胺聚糖、甘油、氨基酸、聚氨基酸、氨基酸类表面活性剂、吡咯烷酮羧酸及其盐、N-乙酰氨基葡糖、动植物性多糖类、辅酶Q10、米粉、白明胶、低聚糖、单糖类、皂角苷类、植物性肽、磷脂、丝胶、清蛋白、软骨素、神经酰胺、胶原、几丁质及壳聚糖等。
作为氨基酸，例如天冬氨酸、苏氨酸、丝氨酸、谷氨酸、瓜氨酸、脯氨酸、甘氨酸、丙氨酸、半胱氨酸、缬氨酸、甲硫氨酸、异亮氨酸、亮氨酸、酪氨酸、苯基丙氨酸、色氨酸、赖氨酸、鸟氨酸、组氨酸、精氨酸等。
作为动植物性多糖类，(1)作为植物性多糖类，例如种子多糖类的瓜尔豆胶、 刺槐豆胶、温柏籽胶、是海藻多糖类的角叉胶、褐藻酸、是树脂多糖类的阿拉伯橡胶、黄芪胶等；(2)作为动物性多糖类，例如鱼肠、鱼鳞等提取的胶原肽。
作为皂角苷类，例如出茶、甘草、人参、竹节人参、大豆、柴胡、七叶胆、丝瓜、远志、风铃草、美远志、麦门冬、木通、麝香草、牛膝、光叶菝葜等含有的来自于植物的物质。
为进一步最大限度利用水分子通道，本发明优选透明质酸作为保湿因子；为进一步促进皮肤的新陈代谢、细胞水合以及皮肤的弹性，本发明选用的透明质酸包括高分子量的透明质酸、中分子量的透明质酸以及低分子量的透明质酸，三种不同种类的透明质酸协同作用，能促进胶原和神经酰胺的合成以及皮肤细胞的迁移与增殖，又可以在皮肤表面实现锁水、补水以及营养角质层的效果，还可以调节免疫细胞活性。
优选地，本发明中所述“高分子量的透明质酸”是指透明质酸钠；所述“中分子量的透明质酸”是指羟丙基三甲基氯化铵透明质酸；所述“低分子量的透明质酸”是指水解透明质酸。申请人发现水解透明质酸、羟丙基三甲基氯化铵透明质酸作为低分子和中分子类透明质酸与大分子类透明质酸，如透明质酸钠协同作用，既能满足低分子或中分子类透明质酸被细胞吸收，从而促进胶原和神经酰胺的合成，以及皮肤细胞的迁移与增殖；同时也具有在肌肤表面锁水、补水，营养角质层的功效。优选地，低分子量的透明质酸、超低分子量的透明质酸以及高分子量的透明质酸的重量比为(0.5～1.5)：(0.5～1.5)：(0.5～1.5)。
本发明对透明质酸钠、水解透明质酸、羟丙基三甲基氯化铵透明质酸的来源不做特别限定，一种实施方式中，透明质酸钠购自Q.P.Corporation,HYALURONSAN HA-LQH；水解透明质酸购自Q.P.Corporation,
羟丙基三甲基氯化铵透明质酸购自Q.P.Corporation,
在本发明体系中，采用了不同跨膜运输方式的协同作用，即本发明体系中还包括“囊泡转运”形式的跨膜运输方式，实现大分子和颗粒物质的膜泡运输，利用囊泡转运与水分子通道协同作用，实现物质的跨屏障运输。一般而言，大分子物质及颗粒性物质不能穿过细胞膜，则需要以膜泡转运的方式实现，即物质在进出细胞的转运过程中都是由膜包裹、形成囊泡、与膜融合或断裂来完成的，但是 在完成膜泡转运过程中实现物质的跨膜运输也是困难重重，细胞膜的脂肪酸外层尾部具有一定程度的疏水作用，脂溶性高的物质容易扩散以及被吸收，而脂溶性低或非脂溶性的物质则较难通过，更难与细胞膜融合，这样就会使得部分营养物质不能被皮肤细胞吸收，从而影响护肤产品在使用时的吸收效果。
本发明基于上述问题的考虑，优选地，在膜泡转运过程中，优先采用囊泡转运方式，在囊泡转运过程中，采用囊泡仿生成分将其承载的有效成分包裹形成纳米微脂囊小球；所述囊泡仿生成分包括但不限于卵磷脂，其成分包括有磷酸、胆碱、脂肪酸、甘油、糖脂、甘油三酸酯以及磷脂。申请人也发现在本发明体系中利用微脂囊小球可实现更好的膜融合，从而实现营养物质的有效包裹与吸收，可能是在本体系中微脂囊小球可以将水溶性的大分子包裹于其间隙中，而脂溶性或者同时具有水溶性与脂溶性的物质结合在其脂质双分子中或亲脂基团中，从而在其与细胞膜融合过程中可以将其承载的有效成分输送至细胞内部，从而实现营养物质的高效吸收。
一般而言，纳米微脂囊小球可以承载用于皮肤修护的各种营养大分子或小分子物质，本发明基于对皮肤抗衰老以及皮肤修护效果的考虑，优选地，纳米微脂囊小球的承载的有效成分包括功能因子以及水分子；进一步，功能因子包括细胞活性促进因子、组织修复因子、低氧诱导调节因子、抗氧化因子中的任一种或多种组合。
在具体工作过程中，囊泡转运可以与水通道识别形式的跨膜运输协同作用，首先在保湿因子作用下，更高效打开水分子通道实现补水，其与纳米微脂囊小球协同作用，实现功能因子的跨屏障高效运输，避免对皮肤屏障的胁迫和损害，又可以在一定程度上促进和修复皮肤的屏障功能。
人体皮肤细胞衰老时，也会伴随着皮肤细胞变差、细胞内氧化压力增大而导致的氧化损伤，同时也会出现细胞呼吸受阻、细胞内氧气含量降低，而氧气感知几乎存在于所有细胞中，表皮的角质形成细胞能在低氧状态下对外界环境做出反应，从而影响促红细胞生成素的产生，调节红细胞的产生和血液的携氧能力。在本发明研究过程中，申请人发现在诱导激活过程中，低氧诱导调节因子通过低氧诱导类物质间接激活细胞活性，这样可以避免出现细胞内活性氧和自由基含量上升，也避免了DNA结构损伤和蛋白酶活性的降低。
进一步地，为实现对损伤和衰老细胞的精准激活，调控皮肤的氧化还原环境，减少皮肤细胞活性的下降以及胶原蛋白的合成受阻等问题。在本发明研究过程中，优选地，采用低氧诱导调节因子在低氧诱导信号下，介导微脂囊小球与靶向细胞膜融合，并释放功能因子以及水分子。在实际工作中，低氧诱导调节因子可以激活损伤和衰老的细胞，从而保证有效的靶向修复，在低氧诱导调节因子作用下，可以与纳米微脂囊小球协同作用，实现其承载的功能因子的靶向精准释放，这是因为在损伤、衰老的皮肤中，细胞呼吸不畅，损伤和衰老的皮肤细胞活力不足，处于低氧状态，可以触发低氧信号，诱导生成低氧诱导因子-1(HIF-1)；而这一低氧诱导信号可以被低氧诱导调节因子迅速捕捉，进而调节HIF-1并参与皮肤细胞的呼吸链过程，实现囊泡的靶向送达与精准释放，再利用其包裹的功能因子，从而提高营养物质的高效利用；实现对损伤、衰老细胞的快速、精准、高效修复；所述低氧诱导调节因子为能感知低氧信号，调节细胞呼吸的物质；例如植物提取物、动物提取物、微生物提取物、脂溶性醌类中的一种或几种组合；作为植物提取物，例如丹参提取物、菊花提取物、泽兰提取物、天麻提取物、人参提取物、黄岑提取物、三七提取物、绿茶提取物、银杏叶提取物、南蛇藤提取物；作为动物提取物，例如蝎毒多肽提取物等；作为微生物提取物，例如酵母提取物等；优选为泛醌，其为一种脂溶性醌类，带有由不同数目(6～10)异戊二烯单位组成的侧链。
基于对膜融合高效性的考虑，本发明采用细胞活性促进因子与微脂囊小球协同作用，促进高活效融合，其能有效促进纤维芽细胞的活性，激活真皮层胶原蛋白生成，同时也参与了红细胞的组成，与铁协同作用，促进组织和黏膜的形成，从而实现与目标细胞膜的高效融合。细胞活性促进因子可以为本领域熟知的组分，例如视黄醇及其衍生物，视黄醇是一种可溶于脂肪的脂溶性维生素，耐高温，而视黄醇衍生物经体内活性代谢产物视黄酸介导两大类视黄酸受体RARs(α、β、γ)和RXRs(α、β、γ)调控基因的表达，形成皮肤的结构蛋白、酶以及细胞外基质等，视黄醇衍生物例如视黄醇棕榈酸酯。
在低氧诱导与囊泡转运相互配合，完成微脂囊小球与目标细胞的融合，实现营养物质的释放之后，需要进行损伤修复的过程；在研究中发现，在损伤修复的过程中，氧化应激通路的信号分子活化蛋白激酶和转录因子进行细胞内的信号传 导，进一步地，纳米微脂囊小球的承载物质对细胞实现靶向修复；为进一步实现皮肤的修复效果，优选地，氧化应激通路的信号分子包括组织修复因子；组织修复因子可以为本领域熟知的组分，选自生长因子、提取物、神经酰胺中的一种或几种组合；作为生长因子，例如表皮生长因子、成纤维细胞生长因子、血管内皮生长因子等；作为提取物包括植物提取物、动物提取物、微生物提取物，例如雪藻提取物、凤尾草提取物、木豆叶提取物、大翅蓟属提取物、乳香提取物、银杏叶提取物、木豆叶提取物、艾叶提取物、动物水解蛋白、蚕丝提取物、蜂胶提取物、鹿茸提取物、胎盘水解物、龟板提取物、美洲大蠊水提取物、酵母提取物等。
进一步优选地，组织修复因子包括神经酰胺；进一步优选地，神经酰胺选自神经酰胺3、神经酰胺4、神经酰胺6II、神经酰胺1、神经酰胺1A、神经酰胺2中的任一种或多种的组合；进一步优选地，神经酰胺为神经酰胺3、神经酰胺6II以及神经酰胺2；进一步优选地，神经酰胺3、神经酰胺6II以及神经酰胺2的质量比为(0.8～1.2)：(0.8～1.2)：(0.8～1.2)；进一步优选地，神经酰胺3、神经酰胺6II以及神经酰胺2的质量比为1：1：1。在修复过程中，申请人发现当神经酰胺作为组织修复因子参与损伤修复过程时，可以有效贴合皮肤，增加角质层的厚度与弹性，从而更好的实现抗损伤以及修复效果。
为进一步优化靶向皮肤修护与抗衰老的效果，申请人发现当采用抗氧化因子与本发明中的其他功能性因子协同作用，可以更好的实现皮肤修护与抗老的效果，申请人在研究中发现清除老化代谢产物以及提高抗氧化酶的活性可以有效延缓皮肤老化以及进行皮肤修护，生育酚能有效减少自由基产生，同时又可以与自由基或活性氧形成稳定态，避免自由基或活性氧对细胞的伤害，还有利于增强细胞端粒酶的活性，促进细胞的修复。抗氧化因子可以为本领域熟知的组分，具有抗氧化自由基作用的物质，选自植物提取物、动物提取物、微生物提取物、维生素、肽类物质、酚类物质、酶中的一种或几种组合；作为植物提取物，例如泽泻提取物、沙棘叶提取物、当归提取物、女贞子提取物、夏枯草提取物、黄岑根提取物、五味子提取物、甘草根提取物、丹参根提取物、木槿花提取物、金盏花提取物等；作为动物提取物，例如美洲大蠊提取物等；作为微生物提取物，例如乳酸菌提取物等；作为维生素类物质，例如维生素A、维生素C、维生素D、维生素E等；作为抗氧化因子为肽类物质，例如米糠肽、还原型谷胱甘肽、大豆肽、 乳蛋白肽等；作为酚类物质，例如生育酚、绿茶多酚、叔丁基对苯二酚等；进一步地，抗氧化因子优选为生育酚，即维生素E的水解产物。
本发明利用通道识别(Channel)、囊泡转运(Transport)、诱导激活(Activation)以及损伤修复(Repair)四个的过程相互配合，利用通道识别为修护改善基础代谢环境，而在囊泡转运过程中利用承载功能因子以及水分子的囊泡级纳米微脂囊小球，更有利于跨屏障运输，且其承载的关键功能因子与之协同作用，实现对受损和衰老的细胞的精准激活，并且在细胞活性促进因子作用下加强细胞间的通信能力，减少自由基的伤害，此外，各种功能因子相互协调作用，实现对皮肤细胞的修护以及抗衰老的效果。
本发明第二方面提供一种所述低氧诱导靶向抗衰修护方法形成的护肤组合物。所述组合物可制备成本领域中通常制备的任何剂型。例如，溶液、悬浮液、乳液、膏、凝胶、面霜、润肤霜、粉、肥皂、含表面活性剂的洗面乳、油、粉状粉底、乳液粉底、蜡状粉底及喷雾等，但不限于此。更具体地，可制备成爽肤水、营养化妆水、营养霜、按摩霜、精华、眼霜、洗面膏、洗面泡沫、洁肤水、面膜、喷雾、粉、干粉、润唇膏、棒状口红、眼影、洗发水及护发素等剂型。此外，优选地，可制备成水包油(Oil-in-Water，O/W)、油包水(Water-in-Oil，W/O)、硅包水(Water-in-Silicone，W/S)、油包水包油(Oil-in-Water-in-Oil，O/W/O)及水包油包水(Water-in-Oil-in-Water，W/O/W)剂型。
一些实施方式中，护肤组合物按照重量百分比计，护肤组合物的原料包括20～80wt％保湿因子、0.1～10wt％细胞活性促进因子、0.01～5wt％低氧诱导调节因子、0.01～20wt％抗氧化因子、0.1～20wt％组织修复因子以及余量水。
本发明的第三方面提供了一种含有所述的护肤组合物的护肤产品，所述产品同样包括任何剂型。例如，溶液、悬浮液、乳液、膏、凝胶、面霜、润肤霜、粉、肥皂、含表面活性剂的洗面乳、油、粉状粉底、乳液粉底、蜡状粉底及喷雾等，但不限于此。更具体地，可制备成爽肤水、营养化妆水、营养霜、按摩霜、精华、眼霜、洗面膏、洗面泡沫、洁肤水、面膜、喷雾、粉、干粉、润唇膏、棒状口红、眼影、洗发水及护发素等剂型。此外，优选地，可制备成水包油(Oil-in-Water，O/W)、油包水(Water-in-Oil，W/O)、硅包水(Water-in-Silicone，W/S)、油包水包油(Oil-in-Water-in-Oil，O/W/O)及水包油包水(Water-in-Oil-in-Water， W/O/W)剂型。
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。
图1：实施例1护肤组合的保湿功效检测结果；
图2：皱纹评价等级示意图；
图3：实施例1护肤组合的淡化皱纹功效检测结果。
以下列举一些具体实施例，但需注意，下列实施例并没有穷举所有可能的情况。并且下述实施例中所用的材料如无特殊说明，均可从商业途径得到。
实施方式仅用于对本发明进行说明，其并不对本发明的保护范围起到限定作用。本发明的保护范围仅由权利要求限定，在本发明公开的实施方式的基础上所做的任何省略、替换或修改将落入本发明的保护范围。
除非另有限定，本文使用的所有技术以及科学术语具有与本发明所属领域普通技术人员通常理解的相同的含义。当存在矛盾时，以本说明书中的定义为准。
实施例1
本实施例提供一种低氧诱导靶向抗衰修护方法，包括通道识别(Channel)、囊泡转运(Transport)、诱导激活(Activation)以及损伤修复(Repair)的过程。
在通道识别过程中，利用天然保湿因子促进水分子通道的开放，调节基础代谢，利用囊泡转运与水分子通道协同作用，实现物质的跨屏障运输。提高了皮肤对水分的吸收能力，同时调节了细胞的基础代谢环境，可以促进后源营养物质的进入；
天然保湿因子为透明质酸；透明质酸包括高分子量的透明质酸、中分子量的透明质酸以及低分子量的透明质酸；高分子量的透明质酸、中分子量的透明质酸以及低分子量的透明质酸的质量比为1:1:1；
所述“高分子量的透明质酸”是指透明质酸钠；所述“中分子量的透明质酸”是指羟丙基三甲基氯化铵透明质酸；所述“低分子量的透明质酸”是指水解透明质 酸；透明质酸钠购自Q.P.Corporation,HYALURONSAN HA-LQH；水解透明质酸购自Q.P.Corporation,
羟丙基三甲基氯化铵透明质酸购自Q.P.Corporation,
在囊泡转运过程中，采用囊泡仿生成分将其承载的有效成分包裹形成纳米微脂囊小球；纳米微脂囊小球承载的有效成分包括功能因子以及水分子；并采用细胞活性促进因子与微脂囊小球协同作用，促进高活效融合。
功能因子包括细胞活性促进因子、组织修复因子、低氧诱导调节因子、抗氧化因子；细胞活性促进因子为视黄醇棕榈酸酯；低氧诱导调节因子为泛醌；抗氧化因子为生育酚；组织修复因子为神经酰胺。
在诱导激活过程中，低氧诱导调节因子通过低氧诱导类物质间接激活细胞活性，这样了可以避免出现细胞内活性氧和自由基含量上升，也避免了DNA结构损伤和蛋白酶活性的降低。低氧诱导调节因子在低氧诱导信号下，介导微脂囊小球与靶向细胞膜融合，并释放功能因子以及水分子；纳米微脂囊小球的承载物质对细胞实现靶向修复。
在损伤修复的过程中，氧化应激通路的信号分子活化蛋白激酶和转录因子进行细胞内的信号传导，神经酰胺作为组织修复因子。
在具体工作过程中，通道识别(Channel)、囊泡转运(Transport)、诱导激活(Activation)以及损伤修复(Repair)四个的过程相互配合，利用通道识别为修护改善基础代谢环境，而在囊泡转运过程中利用承载功能因子以及水分子的囊泡级纳米微脂囊小球，更有利于跨屏障运输，且其承载的关键功能因子与之协同作用，实现对受损和衰老的细胞的精准激活，并且在细胞活性促进因子作用下加强细胞间的通信能力，减少自由基的伤害，此外，各种功能因子相互协调作用，实现对皮肤细胞的修护以及抗衰老的效果。
本实施例还提供了一种利用所述低氧诱导靶向抗衰修护方法形成的护肤组合物，按照重量百分比计，包括45wt％保湿因子、1.5wt％细胞活性促进因子、0.5wt％低氧诱导调节因子、0.8wt％抗氧化因子、1.1wt％组织修复因子以及余量水；
其中，保湿因子为透明质酸；透明质酸包括高分子量的透明质酸、中分子量的透明质酸以及低分子量的透明质酸；高分子量的透明质酸、中分子量的透明质 酸以及低分子量的透明质酸的质量比为1:1:1；
所述“高分子量的透明质酸”是指透明质酸钠；所述“中分子量的透明质酸”是指羟丙基三甲基氯化铵透明质酸；所述“低分子量的透明质酸”是指水解透明质酸；透明质酸钠购自Q.P.Corporation,HYALURONSAN HA-LQH；水解透明质酸购自Q.P.Corporation,
羟丙基三甲基氯化铵透明质酸购自Q.P.Corporation,
细胞活性促进因子为视黄醇棕榈酸酯；低氧诱导调节因子为泛醌；抗氧化因子为生育酚；组织修复因子为神经酰胺3、神经酰胺6II以及神经酰胺2；神经酰胺3、神经酰胺6II以及神经酰胺2的质量比为1：1：1。
在使用过程中可以将上述护肤组合物喷涂于皮肤表面进行吸收。
性能评估
1.保湿功效检测：
选择面部皮肤偏干、缺乏水分的亚洲健康女性受试者35例，年龄为30～55岁。在使用测试产品前和使用后测试脸颊标记区域的皮肤角质层含水量的情况。
检测方式：利用皮肤水分测试仪Corneometer CM825，对脸颊区域测量3次，求取平均值。
检测环境：温度20.1℃～21.2℃，相对湿度48.1％～53.2％。
检测流程如下表1所示：
表1：检测流程安排
统计方法为：
统计分析软件为SPSS。在不同时间点的测量值与基础值比较，使用前后比较，如果值为正态分布，则采用t检验方法进行统计分析；如果值为非正态分布，则采用秩和检验方法进行统计分析；
统计方法均采用双尾检验，检验水准＝0.05。
安全性评价采用统计描述的方法，逐例分析不良事件程度，不良事件持续时间。
变化率即相对使用前的变化率，计算公式如下：
使用产品第1h的△(差值)＝T
1-T
0
使用产品第4h的△(差值)＝T
4-T
0
使用产品第8h的△(差值)＝T
8-T
0
式中，T
0——受试区使用产品前，皮肤参数基础值。
T
1——受试区使用产品后第1h，皮肤参数数值。
T
4——受试区使用产品后第4h，皮肤参数数值。
T
8——受试区使用产品后第8h，皮肤参数数值。
N——受试者人数。
受试者：入组35名受试者，最终统计35名受试者，使用产品为实施例1所得的 护肤组合物。
皮肤角质层含水量Corneometer值检测结果见图1，图中n.s.表示无统计学差异，p>0.05，“*”表示0.01≤p<0.05；“**”表示0.001≤p<0.01；“***”表示p<0.001，通过检测可以知道单次使用产品后的区域在1小时、4小时和8小时的皮肤角质层水分含量与基础值相比均有显著性的上升(p<0.001)，1小时的增长率为71.48％，4小时的增长率为48.02％，8小时的增长率为32.89％。
空白对照区域在1小时的皮肤角质层水分含量与基础值相比无显著性差异(p>0.05)，1小时的下降率为0.07％，空白对照区域在4小时的皮肤角质层水分含量与基础值相比有显著性的下降(0.01<p<0.05)，4小时的下降率为0.9％，空白对照区域在8小时的皮肤角质层水分含量与基础值相比有显著性的下降(p<0.01)，8小时的下降率为1.96％。
通过保湿性检测，可以证明本发明提供的用于靶向抗衰修护的方法形成的护肤组合物对皮肤具有很好的保湿性，能有效保持皮肤表面的水分。
2.淡化皱纹功效检测：
选择面部皮肤满足眼角皱纹等级2～5级(D0)(皱纹等级如图2所示)，且左右眼角皱纹等级没有明显差异而且面部肌肤松弛，面部轮廓及苹果肌下垂的受试者32名，年龄范围在30～55周岁。受试者在使用测试产品前、连用14天及连用28天并由1名专家对受试者在产品使用后的皮肤进行感官评估。产品使用前后的评价结果通过统计学检验方法进行比较从而判断是否有统计学差异。
检测方式：利用皮肤快速光学成像系统PRIMOS lite对眼角区域测量3次，求取平均值。
检测环境：温度20.1℃～21.2℃，相对湿度48.1％～53.2％。
检测流程如下表2所示：
表2：检测流程安排
统计方法为：
统计分析软件为SPSS。在不同时间点的测量值与基础值比较，使用前后比较，如果值为正态分布，则采用t检验方法进行统计分析；如果值为非正态分布，则采用秩和检验方法进行统计分析；
统计方法均采用双尾检验，检验水准＝0.05。
安全性评价采用统计描述的方法，逐例分析不良事件程度，不良事件持续时间。变化率即相对使用前的变化率，计算公式如下：
使用产品2周的△(差值)＝D14-D0
使用产品4周的△(差值)＝D28-D0
使用产品2周的变化率(％)
使用产品4周的变化率(％)
式中，D0——受试区使用产品前，皮肤参数基础值。
D14——受试区使用产品2周，皮肤参数数值。
D28——受试区使用产品4周，皮肤参数数值。
N——受试者人数。
眼角皱纹面积检测结果如图3所示，图中“n.s.”表示无统计学差异；“*”表示0.01≤p<0.05；“**”表示0.001≤p<0.01；“***”表示p<0.001。连续使用实施例2所得护肤组合物28天，受试者的眼角皱纹面积在产品使用14天与基础值相比有显著性下降(p<0.001)，下降率为8.62％；在产品使用28天与基础值相比有显著性下降(p<0.001)，下降率为8.95％。
3.自我评估
选择面部皮肤满足眼角皱纹等级2～5级(D0)(皱纹等级如图2所示)，且左右眼角皱纹等级没有明显差异而且面部肌肤松弛，面部轮廓及苹果肌下垂的受试者32名，年龄范围在30～55周岁，测试结果如下表3所示：
表3：受试者使用实施例所得护肤组合物D28天的评价如下：
*评价指标：1分为“非常不满意”，2分为“不满意”，3分为“一般”，4分为“满意”，5分为“非常满意”，统计N≥4分的人数的占比。
通过淡化皱纹功效检测，可以证明本发明提供的用于靶向抗衰修护的方法形成的护肤组合物对皮肤具有很好的淡化皱纹的功效。
本发明的设计思路和保护范围之内，对上述的具体实施例的其他改动或变型对本领域技术人员来讲是显而易见的。尽管本发明是对照特定实施例进行描述的，但这些实施例的目的只在于例示而不是为了进行限定，相应地，本专利并不仅限于此处描述的几个特定实施例的范围和效果，也不限于与本领域内由发明所取得的进展在某种程度上不一致的其他任何方式。
Claims (10)
- 一种低氧诱导靶向抗衰修护方法，其特征在于，包括通道识别、囊泡转运、诱导激活以及损伤修复的过程。
- 根据权利要求1所述低氧诱导靶向抗衰修护方法，其特征在于，通道识别过程中，利用天然保湿因子促进水分子通道开放，调节基础代谢；利用囊泡转运及水分子通道，实现跨屏障运输。
- 根据权利要求1或2所述低氧诱导靶向抗衰修护方法，其特征在于，囊泡转运过程中，采用囊泡仿生成分将其承载的有效成分包裹形成纳米微脂囊小球；优选地，纳米微脂囊小球承载的有效成分包括功能因子以及水分子。
- 根据权利要求1～3任一项所述低氧诱导靶向抗衰修护方法，其特征在于，诱导激活过程中，低氧诱导调节因子通过低氧诱导类物质间接激活细胞活性。
- 根据权利要求4所述低氧诱导靶向抗衰修护方法，其特征在于，低氧诱导调节因子在低氧诱导信号下，介导微脂囊小球与靶向细胞膜融合，并释放功能因子以及水分子。
- 根据权利要求1～5任一项所述低氧诱导靶向抗衰修护方法，其特征在于，损伤修复的过程中，纳米微脂囊小球承载的有效成分对细胞实现靶向修复。
- 根据权利要求3～6任一项所述低氧诱导靶向抗衰修护方法，其特征在于，功能因子包括细胞活性促进因子、组织修复因子、低氧诱导调节因子、抗氧化因子中的任一种或多种组合。
- 一种根据权利要求1～7任一项所述低氧诱导靶向抗衰修护方法形成的护肤组合物。
- 根据权利要求8所述的护肤组合物，其特征在于，护肤组合物的原料包括20～80wt％保湿因子、0.1～10wt％细胞活性促进因子、0.01～5wt％低氧诱导调节因子、0.01～20wt％抗氧化因子、0.1～20wt％组织修复因子以及余量水。
- 一种含有权利要求8或9所述的护肤组合物的护肤产品。
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| CN111467284A (zh) * | 2020-04-29 | 2020-07-31 | 泉后(广州)生物科技研究院有限公司 | 一种抗衰纳米组合物及其制备方法和应用 |
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