CN112156024A - Hypoxia induction method for targeted anti-aging repair - Google Patents

Hypoxia induction method for targeted anti-aging repair Download PDF

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CN112156024A
CN112156024A CN202011257670.3A CN202011257670A CN112156024A CN 112156024 A CN112156024 A CN 112156024A CN 202011257670 A CN202011257670 A CN 202011257670A CN 112156024 A CN112156024 A CN 112156024A
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hypoxia
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skin
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aging
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不公告发明人
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Vsh Skin Anti Aging Research Institute Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/02Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/14Liposomes; Vesicles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/35Ketones, e.g. benzophenone
    • A61K8/355Quinones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64Proteins; Peptides; Derivatives or degradation products thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/66Enzymes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67Vitamins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9728Fungi, e.g. yeasts
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9771Ginkgophyta, e.g. Ginkgoaceae [Ginkgo family]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783Angiosperms [Magnoliophyta]
    • A61K8/9789Magnoliopsida [dicotyledons]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783Angiosperms [Magnoliophyta]
    • A61K8/9794Liliopsida [monocotyledons]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/98Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
    • A61K8/987Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of species other than mammals or birds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/99Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from microorganisms other than algae or fungi, e.g. protozoa or bacteria
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/08Anti-ageing preparations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/41Particular ingredients further characterized by their size
    • A61K2800/413Nanosized, i.e. having sizes below 100 nm

Abstract

The invention provides a hypoxia induction method for targeted anti-aging repair, which is characterized in that vesicle bionic components are divided into nanoscale liposome globules, and hypoxia induction regulatory factors and antioxidant factors are wrapped to realize induction activation and damage repair. The hypoxia induction regulatory factor captures hypoxia induction factor-1 generated by hypoxia signal induction in a hypoxia state, further regulates the generation of the hypoxia induction factor-1, participates in the respiratory chain process of skin cells, realizes the targeted delivery and accurate release of vesicles, efficiently utilizes nutrients, and realizes the rapid, accurate and efficient repair of damaged and aged cells by utilizing various factors participating in vesicle transport.

Description

Hypoxia induction method for targeted anti-aging repair
Technical Field
The invention relates to the technical field related to skin repair, and particularly provides a hypoxia induction method for targeted anti-aging repair.
Background
Oxygen sensing exists in almost all cells, cells in the surface layer and the deep layer of the skin have oxygen sensing capacity, and keratinocytes in the surface layer can respond to the external environment in a low-oxygen state. The skin aging is the result that skin is continuously accumulated after being insufficiently repaired after undergoing a series of injuries, the current human knowledge on skin aging is promoted to the cell and molecular level, when the microenvironment of human skin is deteriorated, cell respiration is blocked, the oxygen content in partial cells is reduced, and oxidative stress reaction is aggravated when the skin is in a low oxygen state for a long time, so that the content of active oxygen and free radicals is sharply increased, cells are exposed to peroxidation pressure, and further DNA structure damage and protease activity reduction are caused. The physical and chemical damages lead to the reduction of the activity of skin cells, the obstruction of the synthesis of collagen, the accelerated aging and the death of the skin cells and the appearance of the early-aged marks of the skin.
Sufficient oxygen is essential for cellular respiration and repair of its damage. The cells lose oxygen and vitality and become shriveled, so that the death and skin aging of the cells are accelerated, the damaged and aged skin cells of a human body take the lead, and therefore, how to accurately induce and activate the damaged and aged skin cells in a hypoxia environment by using a hypoxia induction regulation method is important, so that various nutrients and growth factors which are conveyed upstream accurately act on the cells through target sites, the vitality of the skin cells is mobilized, and the activity of the skin cells is enhanced.
Disclosure of Invention
In order to solve the above problems, the present invention provides, in a first aspect, a hypoxia inducible method for targeted anti-aging repair, in which vesicle biomimetic components are divided into nanoscale liposome globules, and hypoxia inducible regulatory factors and antioxidant factors are wrapped to achieve induction activation and damage repair.
The vesicle biomimetic component includes, but is not limited to, lecithin, which includes, phosphate, choline, fatty acid, glycerol, glycolipid, triglyceride, and phospholipid.
In one embodiment, the aqueous cavity of the liposome is coated with a water-soluble macromolecular substance, and the lipid-soluble substance or the substances with both water solubility and lipid solubility are combined in a lipid bimolecular or lipophilic group.
The liposome globule is a vesicle-level microencapsulated multi-layer liposome with a molecular diameter of only tens of nanometers formed by liposome encapsulation and high-pressure emulsification. The outside of the micro lipid capsule ball is respectively provided with a hydrophilic end capable of being dissolved in water and a hydrophobic end capable of being dissolved in oil, and the micro lipid capsule has good permeability and solubility in both aqueous substances and oily substances. The phospholipid content of the liposome is the same as that of human cell membrane molecules. The phospholipid membrane is composed of lipophilic and hydrophilic molecules which are arranged oppositely and form a structure which is coiled like an onion.
The liposome encapsulation and high-pressure emulsification techniques are conventional techniques known to those skilled in the art, and are not particularly limited.
The hypoxia inducible regulatory factor realizes accurate induced activation of damaged and aged cells under oxidative stress caused by a hypoxic state.
Oxygen is an essential substance for the body to metabolize, and the oxygen deficiency reaction is a strong stress behavior of the body and cells. When human skin cells are aged, the skin cells are also deteriorated, the oxidation damage caused by the increase of the oxidation pressure in the cells is increased, the cell respiration is blocked, the oxygen content in the cells is reduced, the oxygen sensing almost exists in all cells, the keratinocyte of the epidermis can react to the external environment in a low oxygen state, so that the generation of erythropoietin is influenced, the generation of red blood cells and the oxygen carrying capacity of blood are adjusted, the repair and the regeneration of capillary vessels are promoted, the skin microcirculation is improved, and red blood filaments caused by the stasis of blood vessel walls are avoided.
In one embodiment, the microcapsule globules are wrapped with hypoxia-inducible regulatory factor, capture hypoxia-inducible factor-1 induced by hypoxia signals in a hypoxic state, further regulate the generation of hypoxia-inducible factor-1 and participate in the respiratory chain process of skin cells, and realize precise induction and activation of damaged and aged cells.
Specifically, in damaged and aged skin, the cells are not breathed smoothly, and the damaged and aged skin cells are not viable and in a low oxygen state, so that a hypoxia signal is triggered to induce and generate hypoxia inducible factor-1; the hypoxia induction signal can be rapidly captured by hypoxia induction regulating factors participating in vesicle transport, further regulates the generation of hypoxia induction factor-1, participates in the respiratory chain process of skin cells, realizes the targeted delivery and accurate release of vesicles, and efficiently utilizes nutrients and activates the respiration of damaged and aged cells; meanwhile, other various factors transported by the vesicles are utilized to realize quick, accurate and efficient repair of damaged and aged cells.
In one embodiment, the hypoxia inducible regulator activates cellular respiration and is capable of regulating genes acting on the cellular respiratory chain, inhibiting mitochondrial peroxidation, and protecting the integrity of the biofilm structure and lipid barrier.
In one embodiment, the hypoxia inducible regulatory factor is a substance that senses a hypoxic signal and regulates cellular respiration.
In one embodiment, the hypoxia inducible regulatory factor is a substance capable of sensing hypoxia signals and regulating cellular respiration, and is selected from one or more of plant extracts, animal extracts, microbial extracts and fat-soluble quinones.
In a preferred embodiment, the hypoxia inducible regulatory factor is a plant extract including, but not limited to, salvia miltiorrhiza extract, chrysanthemum extract, eupatorium japonicum extract, gastrodia elata extract, ginseng extract, scutellaria baicalensis extract, panax notoginseng extract, green tea extract, ginkgo biloba extract, celastrus orbiculatus extract.
In a preferred embodiment, the hypoxia inducible regulator is an animal extract, including but not limited to scorpion venom polypeptide extract.
In a preferred embodiment, the hypoxia inducible regulator is a yeast extract, including but not limited to yeast extract.
In a preferred embodiment, the hypoxia inducible regulator is a lipid soluble quinone; including but not limited to ubiquinone.
The ubiquinone is a fat-soluble quinone with side chains consisting of different numbers (6-10) of isoprene units.
The ubiquinone is the only fat-soluble and endogenous antioxidant, is an important component of the electron transfer chain of mitochondria of most eukaryotic cells, and plays an important role in generating adenosine triphosphate and inhibiting cell membrane peroxidation in the aerobic respiration process of the cells.
The ubiquinone is generally used as an antioxidant for the skin against oxidative aging, and is a single anti-aging ingredient. The anti-aging health-care product takes part in the hypoxia induction regulation process of human skin by virtue of the hypoxia induction regulation function of ubiquinone, and is matched with other effective components to perform synergistic anti-aging. Ubiquinone indirectly activates skin cell activity through hypoxia-inducible substances, participates in energy production and activation, and is an activator of cell metabolism and cell respiration. Under the oxidative stress of the cells, the compounds are used as important hydrogen carriers in the respiratory chain of the cells, can participate in the oxidative phosphorylation and ATP generation processes, and regulate the redox environment of the cells.
In the process of human skin cell damage and aging, oxidative damage caused by the respiratory deterioration of skin cells and the increase of cell oxidative stress is a key factor of skin cell aging. The invention discovers that the microcapsule globules are wrapped with the antioxidant factors, and can participate in the antioxidant aging of skin cells under the action of hypoxia-induced regulatory factors to reduce oxidative damage.
In one embodiment, the antioxidant factor combines with free radicals or reactive oxygen species to form a stable low energy state, blocking chain reactions of liposome free radicals and preventing cell damage from excessive oxidation.
In one embodiment, the antioxidant factor acts on cell telomerase to enhance the activity of the telomerase, extend the length of telomeres on both sides of a chromosome, and repair cell damage.
The hypoxia-inducible regulatory factor can assist the antioxidant factor to be converted into a stable state in cells, and the antioxidant factor and the cell can synergistically play an antioxidant role to resist skin aging.
In one embodiment, the antioxidant factor is a substance having an effect of resisting free radicals, and is selected from one or more of plant extract, animal extract, microorganism extract, vitamins, peptide substances, phenolic substances and enzymes.
In a preferred embodiment, the antioxidant factor is a plant extract including, but not limited to, an extract of alisma orientale, an extract of hippophae rhamnoides, an extract of angelicae gigantis radix, an extract of ligustrum lucidum, an extract of prunella vulgaris, an extract of scutellaria baicalensis roots, an extract of schizandrae fructus, an extract of glycyrrhiza uralensis roots, an extract of salvia miltiorrhiza roots, an extract of hibiscus flowers, an extract of calendula officinalis flowers.
In a preferred embodiment, the antioxidant factor is an animal extract, including but not limited to periplaneta americana extract.
In a preferred embodiment, the antioxidant factor is a microbial extract, including but not limited to a lactic acid bacteria extract.
In a preferred embodiment, the antioxidant factor is a vitamin, including but not limited to vitamin a, vitamin C, vitamin D, vitamin E.
In a preferred embodiment, the antioxidant factor is a peptide substance including, but not limited to, rice bran peptide, reduced glutathione, soybean peptide, milk protein peptide.
In a preferred embodiment, the antioxidant factor is a phenolic substance including, but not limited to, tocopherol, green tea polyphenol, t-butyl hydroquinone.
In a preferred embodiment, the antioxidant factor is an enzyme, including but not limited to superoxide dismutase, catalase, glutathione peroxidase.
In a more preferred embodiment, the antioxidant factor is preferably a tocopherol, i.e. a hydrolysate of vitamin E.
The tocopherol has natural antioxidant activity and structurally mainly depends on a hydroxyl group at the 6 th position of a benzene ring as an active site; can effectively reduce the generation of free radicals, can form a stable state with the free radicals or active oxygen, avoids the damage of the free radicals or the active oxygen to cells, is favorable for enhancing the activity of cell telomerase and promotes the repair of the cells.
In one embodiment, the liposome globules further encapsulate a cell activity promoting factor and a tissue repair factor.
The cell activity promoting factor has natural receptors in a human body, encodes and generates structural proteins, enzymes, extracellular matrix and the like of the skin, and can stimulate the generation of collagen in a dermis layer and restore the elasticity of aged skin by promoting the activity of fibroblasts; in addition, the red blood cell composition is also involved, and the red blood cell composition can be used for improving the aging and sensitive skin hematopoietic microenvironment under the synergistic effect with iron; is involved in the generation of skin epithelial tissues, can promote the formation of tissues and mucous membranes, and maintain the integrity of epithelial cells. In addition, under the action of the hypoxia-induced regulatory factor, the cell activity promoting factor participates in vesicle transport, targeted scheduling and transportation are carried out by virtue of the vesicle transport and hypoxia regulation system of the human body, and the cell activity promoting factor is preferentially distributed to damaged and aged cells in a hypoxic state, so that the damaged and aged cells are quickly, accurately and efficiently repaired.
The cell activity promoting factor is retinol and derivatives thereof, and is selected from one or more of retinol, retinal, hydrogenated retinol, retinol acetate, retinol palmitate, retinol linoleate, retinol propionate, retinol retinoic acid ester and retinol acetate; preferably, the cell activity promoting factor is retinol palmitate.
The tissue repair factor is a key signal molecule of an oxidative stress pathway in cells, activates various protein kinases and transcription factors, participates in intracellular signal conduction, and performs membrane fusion repair. In addition, under the action of the hypoxia-induced regulatory factor, the cell activity promoting factor participates in vesicle transport, targeted scheduling and transportation are carried out by virtue of the vesicle transport and hypoxia regulation system of the human body, and the cell activity promoting factor is preferentially distributed to damaged and aged cells in a hypoxic state, so that the damaged and aged cells are quickly, accurately and efficiently repaired.
The tissue repair factor is selected from any one of epidermal growth factor, fibroblast growth factor, ceramide and vascular endothelial growth factor; preferably, the tissue repair factor is nano-scale anthropomorphic ceramide, and is selected from one or a combination of more of ceramide 3, ceramide 4, ceramide 6II, ceramide 1A and ceramide 2; preferably, the tissue repair factor is ceramide 3, ceramide 6II, and ceramide 2; the mass ratio of the ceramide 3 to the ceramide 6II to the ceramide 2 is (0.8-1.2): (0.8-1.2): (0.8 to 1.2); preferably, the mass ratio of the ceramide 3 to the ceramide 6II to the ceramide 2 is 1: 1: 1.
through the participation of various factors and the fusion and repair of membranes, the accurate induction and activation of damaged and aged cells of the dermis are realized, and the skin microcirculation is improved; the multi-factor interaction further strengthens the communication capacity among cells, protects the cells from being damaged by free radicals, better promotes the generation of collagen and solves the problems of skin sensitivity and aging.
In the invention, the ubiquinone is an important hypoxia induction regulatory factor, and can sense the existence of hypoxia signals under the action of a vesicle transport and hypoxia regulation system and a hypoxia induction factor-1, so as to carry out targeted activation and accurate repair on skin. However, the low water solubility of ubiquinone and the barrier function of the stratum corneum make it difficult to deliver ubiquinone to deeper layers of skin.
In the invention, ubiquinone is loaded on the liposome globules, and the targeted induction and revitalization of the antioxidant factors, the cell activity promoting factors and the tissue repair factors which are wrapped by the ubiquinone on skin cells can be realized by virtue of vesicle transport and hypoxia induction regulation processes. Various functional factors and the liposome globules are mutually coordinated, so that the double-layer purpose that various skin functional factors penetrate into the deep layer of the skin layer by layer and are released slowly after being delivered in a targeted manner is realized, and the accurate anti-aging and long-acting repair of the aged skin are further realized.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.
FIG. 1: example 2 moisturizing efficacy test results of skin care combinations;
FIG. 2: a schematic diagram of wrinkle evaluation ratings;
FIG. 3: example 2 wrinkle lightening efficacy test results for skin care combinations;
FIG. 4: example 2 wrinkle reduction expert evaluation test results for skin care combinations;
FIG. 5: example 2 skin care combination skin elasticity R5 value test results;
FIG. 6: example 2 skin shine test results for skin care combinations;
FIG. 7: example 2 skin care combination skin stratum corneum moisture content test results;
FIG. 8: example 2 skin care combination skin transdermal water loss test results;
FIG. 9: example 2 expert clinical assessment (fineness) test results of skin care combinations.
Detailed Description
Some specific examples are listed below, but it should be noted that the following examples are not exhaustive of all possible cases. And the materials used in the following examples are commercially available unless otherwise specified.
The embodiments are only for illustrating the present invention and do not limit the scope of the present invention. The scope of the present invention is defined only by the appended claims, and any omissions, substitutions, or modifications made based on the embodiments disclosed herein will fall within the scope of the present invention.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In case of conflict, the present specification, including definitions, will control.
Example 1
This example 1 provides a hypoxia-induced method for targeted anti-aging repair, which divides vesicle biomimetic components into nanoscale liposome globules, and encapsulates hypoxia-induced regulatory factors and antioxidant factors to achieve induction activation and damage repair.
The water-based cavity of the liposome pellet is coated with water-soluble macromolecular substances, and fat-soluble or water-soluble and fat-soluble substances are combined in lipid bimolecules or lipophilic groups of the liposome pellet.
The hypoxia induction regulatory factor captures hypoxia induction factor-1 generated by hypoxia signal induction in a hypoxia state, further regulates the generation of the hypoxia induction factor-1, participates in the respiratory chain process of skin cells, and realizes accurate induction activation of damaged and aged cells.
The hypoxia-inducible regulatory factor regulates and controls genes to activate cell respiration, can act on a cell respiratory chain, inhibits the peroxidation of mitochondria, and protects the integrity of a biological membrane structure and a lipid barrier.
The hypoxia inducible regulatory factor is ubiquinone.
The antioxidant factor is combined with free radicals or active oxygen to form a stable low energy state, so that the chain reaction of liposome free radicals is blocked, and the cell damage caused by excessive oxidation is prevented.
The antioxidant factor acts on cell telomerase to enhance the activity of the cell telomerase, extend the length of telomeres on two sides of a chromosome and realize cell damage repair.
The antioxidant factor is tocopherol.
The liposome globules are also wrapped with cell activity promoting factors and tissue repair factors.
Example 2
This example 2 provides a method for targeted anti-aging repair comprising hypoxia induction; also includes the channel recognition and opening, vesicle transport process.
In the hypoxia induction process, vesicle bionic components are divided into nano-scale liposome globules which are wrapped by hypoxia induction regulatory factors and antioxidant factors, so that the induction activation and damage repair are realized.
The hypoxia inducible regulatory factor is ubiquinone.
The antioxidant factor is tocopherol.
In the process of channel identification and opening, the channel identification and opening are completed by utilizing the moisturizing factor and the liposome pellets, so that the trans-skin barrier and trans-cell membrane transportation of substances is realized.
The moisturizing factor is hyaluronic acid; the hyaluronic acid comprises high molecular weight hyaluronic acid, medium molecular weight hyaluronic acid and low molecular weight hyaluronic acid; the high molecular weight hyaluronic acid is sodium hyaluronate; the hyaluronic acid with medium molecular weight is hydroxypropyl trimethyl ammonium chloride hyaluronic acid; the low molecular weight hyaluronic acid is hydrolyzed hyaluronic acid; the mass ratio of the high molecular weight hyaluronic acid to the medium molecular weight hyaluronic acid to the low molecular weight hyaluronic acid is 1: 1: 1.
the sodium hyaluronate is available from Q.P.corporation, HYALURONSAN HA-LQH; hydrolyzed hyaluronic acid was purchased from q.p.corporation,
Figure BDA0002773573050000081
hydroxypropyltrimethylammonium chloride hyaluronic acid is available from q.p.corporation,
Figure BDA0002773573050000082
-P。
in the vesicle transport process, vesicle bionic components are divided into nanoscale liposome globules which are wrapped by cell activity promoting factors and tissue repair factors, and membrane fusion repair and intercellular transport are realized.
The cell activity promoting factor is retinol propionate; the tissue repair factor is ceramide 3, ceramide 6II and ceramide 2; the mass ratio of the ceramide 3 to the ceramide 6II to the ceramide 2 is 1: 1: 1.
the embodiment also provides a skin care composition for targeted anti-aging repair, which comprises 45 wt% of moisturizing factor, 1.5 wt% of cell activity promoting factor, 0.5 wt% of hypoxia-inducible regulatory factor, 0.8 wt% of antioxidant factor, 1.1 wt% of tissue repair factor and the balance of water in percentage by weight;
wherein the moisturizing factor is hyaluronic acid; the hyaluronic acid comprises high molecular weight hyaluronic acid, medium molecular weight hyaluronic acid and low molecular weight hyaluronic acid; the mass ratio of the high molecular weight hyaluronic acid to the medium molecular weight hyaluronic acid to the low molecular weight hyaluronic acid is 1: 1: 1;
the high molecular weight hyaluronic acid is sodium hyaluronate; the hyaluronic acid with medium molecular weight is hydroxypropyl trimethyl ammonium chloride hyaluronic acid; the low molecular weight hyaluronic acid is hydrolyzed hyaluronic acid;
the sodium hyaluronate is available from Q.P.corporation, HYALURONSAN HA-LQH; hydrolyzed hyaluronic acid was purchased from q.p.corporation,
Figure BDA0002773573050000083
hydroxypropyltrimethylammonium chloride hyaluronic acid is available from q.p.corporation,
Figure BDA0002773573050000084
-P。
the cell activity promoting factor is retinol palmitate; the hypoxia inducible regulatory factor is ubiquinone; the antioxidant factor is tocopherol; the tissue repair factor is ceramide 3, ceramide 6II and ceramide 2; the mass ratio of the ceramide 3 to the ceramide 6II to the ceramide 2 is 1: 1: 1.
in the using process, the cell activity promoting factor, the hypoxia induction regulatory factor, the antioxidant factor and the tissue repair factor are wrapped in the microcapsule globule, and then the microcapsule globule is mixed with the moisturizing factor and the water and sprayed on the surface of the skin for absorption.
Performance evaluation
1. And (3) moisture retention efficacy detection:
35 Asian healthy female subjects with dry facial skin and water shortage are selected, and the age is 30-55 years. The moisture content of the stratum corneum in the cheek marker area was tested before and after application of the test product.
The detection mode is as follows: the cheek area was measured 3 times using a skin moisture tester Corneometer CM825, and the average was calculated.
Detecting the environment: the temperature is 20.1-21.2 ℃, and the relative humidity is 48.1-53.2%.
The detection procedure is shown in table 1 below:
table 1: detection flow arrangement
Figure BDA0002773573050000091
The statistical method comprises the following steps:
the statistical analysis software was SPSS. Comparing the measured values at different time points with the basic values, comparing before and after use, and if the values are in normal distribution, performing statistical analysis by adopting a t test method; if the value is in non-normal distribution, carrying out statistical analysis by adopting a rank sum test method;
the statistical method adopts two-tail test, and the test level is 0.05.
The safety evaluation adopts a statistical description method to analyze the adverse event degree and the adverse event duration case by case.
The change rate is calculated by the following formula relative to the change rate before use:
delta (difference) of 1h using the product1-T0
Delta (difference) of 4h using the product4-T0
Delta (difference) of 8h using the product8-T0
Figure BDA0002773573050000101
Figure BDA0002773573050000102
Figure BDA0002773573050000103
In the formula, T0Skin parameter base values before the product is applied to the test area.
T1-skin parameter values 1h after application of the product in the test area.
T44h after application of the product in the test area, the skin parameter values.
T8-skin parameter values at 8h after application of the product to the test area.
N-number of subjects.
Subject: 35 subjects were enrolled, and finally, 35 subjects were counted, and the skin care composition obtained in example 2 was used as the product.
The detection result of the Corneometer value of the water content of the stratum corneum is shown in figure 1, wherein n.s. represents no statistical difference, p is greater than 0.05, and "+" represents that p is greater than or equal to 0.01 and less than 0.05; "+" indicates 0.001. ltoreq. p < 0.01; ". indicates p <0.001, and it was found by examination that the moisture content of the stratum corneum in the area after a single use of the product was significantly increased (p <0.001) at 1 hour, 4 hours, and 8 hours compared to the base value, with an increase of 71.48% at 1 hour, 48.02% at 4 hours, and 32.89% at 8 hours.
The water content of the horny layer of the skin in the blank control area at 1 hour is not significantly different from the basic value (p >0.05), the reduction rate at 1 hour is 0.07%, the water content of the horny layer of the skin in the blank control area at 4 hours is significantly reduced from the basic value (0.01< p <0.05), the reduction rate at 4 hours is 0.9%, the water content of the horny layer of the skin in the blank control area at 8 hours is significantly reduced from the basic value (p <0.01), and the reduction rate at 8 hours is 1.96%.
Through moisture retention detection, the skin care composition formed by the method for targeted anti-aging repair provided by the invention has good moisture retention on skin and can effectively retain moisture on the surface of the skin.
2. And (3) wrinkle fading efficacy detection:
32 subjects whose facial skin satisfied the canthus wrinkle level of 2 to 5 (D0) (wrinkle level shown in FIG. 2), had loose facial skin and sagging facial contour and apple muscle, and had ages of 30 to 55 years. The subjects had a sensory evaluation of the skin of the subjects after the use of the product before, 14 days and 28 days after the use of the test product by 1 expert. The evaluation results before and after the product is used are compared by a statistical test method to judge whether the product has statistical difference.
The detection mode is as follows: the angular region of the eye was measured 3 times using the PRIMOS lite, a fast optical imaging system for the skin, and averaged.
Detecting the environment: the temperature is 20.1-21.2 ℃, and the relative humidity is 48.1-53.2%.
The detection scheme is shown in table 2 below:
table 2: detection flow arrangement
Figure BDA0002773573050000111
Figure BDA0002773573050000121
The statistical method comprises the following steps:
the statistical analysis software was SPSS. The measured values at different time points are compared with the base values, using a pre-and post-comparison,
if the value is normal distribution, performing statistical analysis by adopting a t test method; if the value is not normally distributed, then
Carrying out statistical analysis by adopting a rank sum test method;
the statistical method adopts two-tail test, and the test level is 0.05.
The safety evaluation adopts a statistical description method to analyze the adverse event degree and the adverse event duration case by case.
The change rate is calculated by the following formula relative to the change rate before use:
delta (difference) of 2 weeks using the product D14-D0
Delta (difference) of 4 weeks using the product D28-D0
Change ratio (%) of 2 weeks using the product
Change ratio (%) of 4 weeks using the product
Where D0-skin parameter base before product application to the test area.
D14-skin parameter values for 2 weeks of product use in test area.
D28-skin parameter values for 4 weeks of product use in test area.
N-number of subjects.
The detection result of the area of the canthus wrinkles is shown in fig. 3, wherein n.s. in the figure indicates that no statistical difference exists; "+" indicates 0.01. ltoreq. p < 0.05; "+" indicates 0.001. ltoreq. p < 0.01; "x" indicates p < 0.001. After 28 days of continuous use of the skin care composition obtained in example 2, the area of canthus wrinkles of the tested person is significantly reduced (p <0.001) compared with the basic value in 14 days of use of the product, and the reduction rate is 8.62%; compared with the basic value, the product has a remarkable reduction (p is less than 0.001) in 28 days of use, and the reduction rate is 8.95%.
The expert evaluation results are shown in fig. 4, wherein "n.s." means no statistical difference; "+" indicates 0.01. ltoreq. p < 0.05; "+" indicates 0.001. ltoreq. p < 0.01; "x" indicates p < 0.001. After 28 consecutive days of use of the skin care composition obtained in example 2, the expert clinical evaluation of the subjects (canthus wrinkles) showed a significant decrease (p <0.001) compared to the base value at 14 days of use of the product, with a decrease rate of 9.91%; compared with the basic value, the product has a remarkable reduction (p <0.001) in 28 days of use, and the reduction rate is 24.32%.
32 subjects who were selected to have facial skin satisfying the canthus wrinkle rating of 2 to 5 (D0) (wrinkle rating shown in fig. 2), had no significant difference in the right and left canthus wrinkle ratings, had loose facial skin, facial contour and apple myofacial sagging, and had ages ranging from 30 to 55 years old, and the self-assessment test results are shown in table 3 below:
table 3: the subjects were evaluated using the skin care composition obtained in example 2 for D28 days as follows:
Figure BDA0002773573050000131
evaluation index: 1 is divided into 'very unsatisfactory', 2 is divided into 'unsatisfactory', 3 is divided into 'normal', 4 is divided into 'satisfactory', 5 is divided into 'very satisfactory', and the percentage of people with N being more than or equal to 4 is counted.
The wrinkle-lightening efficacy test proves that the skin care composition formed by the method for targeted anti-aging repair has good wrinkle-lightening efficacy on the skin.
3. And (3) detecting the overall effect of the skin:
35 Asian healthy female subjects with dry facial skin and water shortage are selected, and the age range is 30-55 years old. The subjects were tested for skin moisture, skin elasticity R5, skin moisture loss through skin, skin gloss before, 14 days and 28 days of use of the test products, respectively, and the subjects' skin after use of the products was subjected to sensory evaluation by 1 expert. The evaluation results before and after the product is used are compared by a statistical test method to judge whether the product has statistical difference.
The detection mode is as follows:
moisture content of skin stratum corneum: measuring the cheek area 3 times by a skin moisture tester Corneometer CM825, and calculating an average value;
percutaneous water loss: measuring the cheek area 3 times by using a skin moisture and running water tester Tewameter TM 300, and calculating an average value;
skin glossiness: measuring cheek area 3 times with Glossimeter GL200 to obtain average value;
skin melanin: measuring the cheek area 3 times by using a skin melanin and heme tester Mexameter MX18, and calculating an average value;
skin elasticity: measuring the cheek area for 3 times by using a skin elasticity tester Cutomer dual MPA580, and calculating an average value;
and (4) expert evaluation: the smoothness of the facial skin of the subjects was evaluated clinically by 1 expert before, at 14 and 28 days of sample application, and the specific scoring criteria were: 1 minute to 7 minutes represent very coarse-not fine at all-very fine.
Detecting the environment: the temperature is 20.1-21.2 ℃, and the relative humidity is 48.1-53.2%.
The detection scheme is shown in table 4 below:
table 4: detection flow arrangement
Figure BDA0002773573050000141
Figure BDA0002773573050000151
The statistical method comprises the following steps:
the statistical analysis software was SPSS. Comparing the measured values at different time points with the basic values, comparing before and after use, and if the values are in normal distribution, performing statistical analysis by adopting a t test method; if the value is in non-normal distribution, carrying out statistical analysis by adopting a rank sum test method;
the statistical method adopts two-tail test, and the test level is 0.05.
The safety evaluation adopts a statistical description method to analyze the adverse event degree and the adverse event duration case by case.
The change rate is calculated by the following formula relative to the change rate before use:
delta (difference) of 2 weeks using the product D14-D0
Delta (difference) of 4 weeks using the product D28-D0
Figure BDA0002773573050000152
Figure BDA0002773573050000161
Where D0-skin parameter base before product application to the test area.
D14-skin parameter values for 2 weeks of product use in test area.
D28-skin parameter values for 4 weeks of product use in test area.
N-number of subjects.
Subject: 35 subjects were enrolled and a final statistics of 33 subjects was made, two of which were withdrawn from the test for other reasons, using a skin care composition as obtained in example 2.
The detection result of the skin elasticity R5 value is shown in figure 5, wherein n.s. represents no statistical difference, "+" represents 0.01 ≦ p < 0.05; (ii) a "+" indicates 0.001. ltoreq. p < 0.01; ". indicates p < 0.001. by testing, it was found that the skin elasticity R5 value of the subject was significantly increased (p <0.001) from the baseline value at 14 days of product use for 28 consecutive days of the skin care composition obtained in example 2, with a 6.30% increase rate; the product has a significant increase (p <0.001) compared with the basic value at 28 days of use, and the increase rate is 13.19%.
The skin gloss measurements are shown in FIG. 6, where n.s. indicates no statistical difference, "-" indicates 0.01. ltoreq. p < 0.05; (ii) a "+" indicates 0.001. ltoreq. p < 0.01; ". indicates p < 0.001. by examination, it was found that the skin gloss of the subjects was significantly increased (p <0.001) from the base value at 14 days of product use by 28 days of continuous use of the skin care composition obtained in example 2, with a 10.06% increase rate; the product has a significant increase (p <0.001) compared with the basic value at 28 days of use, and the increase rate is 19.33%.
The water content of the horny layer of the skin is shown in figure 7, wherein n.s. shows no statistical difference, and "+" shows that p is more than or equal to 0.01 and less than 0.05; (ii) a "+" indicates 0.001. ltoreq. p < 0.01; ". indicates p < 0.001. by testing, it was found that the skin care composition obtained in example 2 was significantly increased in the water content of the stratum corneum of the subject (p <0.001) from the basal value at 14 days of product use, with a 30.27% increase rate, for 28 consecutive days; the product has a remarkable increase (p <0.001) compared with the basic value in 28 days of use, and the increase rate is 59.23%.
The skin percutaneous water loss detection result is shown in figure 8, wherein n.s. shows no statistical difference, and "+" shows that p is more than or equal to 0.01 and less than 0.05; (ii) a "+" indicates 0.001. ltoreq. p < 0.01; ". indicates p < 0.001. it can be seen from the test that the skin care composition obtained in example 2 was used for 28 days continuously, the skin transdermal water loss of the subject was significantly reduced (p <0.001) compared with the base value in 14 days of the product use, and the reduction rate was 14.54%; compared with the basic value, the product has a remarkable reduction (p <0.001) in 28 days of use, and the reduction rate is 18.98%.
The results of expert clinical evaluation (fineness) are shown in fig. 9, wherein n.s. indicates no statistical difference, "+" indicates 0.01. ltoreq. p < 0.05; (ii) a "+" indicates 0.001. ltoreq. p < 0.01; ". indicates p <0.001, and it was found by examination that the skin care composition obtained in example 2 was used for 28 consecutive days, the expert clinical evaluation (fineness) of the subjects showed a significant increase (p <0.001) compared to the base value at 14 days of product use, with a 15.17% increase rate; the product has a remarkable increase (p <0.001) compared with the basic value in 28 days of use, and the increase rate is 28.97%.
Self-assessment
The results of the subject self-assessment test are shown in table 5 below:
table 5: the subjects were evaluated using the skin care composition obtained in example 2 for D28 days as follows:
Figure BDA0002773573050000171
evaluation index: 1 is divided into 'very unsatisfactory', 2 is divided into 'unsatisfactory', 3 is divided into 'normal', 4 is divided into 'satisfactory', 5 is divided into 'very satisfactory', and the percentage of people with N being more than or equal to 4 is counted.
After using the skin care composition obtained in example 2 for 28 days, 90.91% of subjects considered the skin moistening effect to be significantly improved, 93.94% of subjects considered the skin moisturizing effect to be significantly improved, 93.94% of subjects considered the skin smoothness to be significantly improved, 90.91% of subjects considered the skin tendering effect to be significantly improved, 81.82% of subjects considered the glossiness to be significantly improved, 93.94% of subjects considered the product mildness to be satisfied, and 96.97% of subjects considered the product overall satisfaction.
In summary, the skin care composition obtained in example 2 has the effects of moisturizing, repairing skin barrier function, improving glossiness and enhancing elasticity.
Other variations and modifications to the specific embodiments described above will be apparent to those skilled in the art, which will be within the spirit and scope of the invention. Although the present invention has been described in relation to particular embodiments thereof, which are intended to be illustrative and not restrictive, the scope of the invention is not to be limited to the specific embodiments shown and described herein, nor is it limited to any specific form or manner which is inconsistent with the progress in the art and that which is believed to be achieved by the invention.

Claims (10)

1. A hypoxia induction method for targeted anti-aging repair is characterized in that vesicle bionic components are divided into nanoscale liposome globules, and hypoxia induction regulatory factors and antioxidant factors are wrapped to realize induction activation and damage repair.
2. A hypoxia-inducible method for targeted anti-aging therapy according to claim 1, wherein the aqueous cavities of the liposome beads are coated with water-soluble macromolecular substances, and lipid-soluble or both water-soluble and lipid-soluble substances are incorporated in lipid bimolecules or lipophilic groups thereof.
3. A hypoxia-inducible method for targeted anti-aging repair according to claim 1, wherein the hypoxia-inducible regulatory factor captures hypoxia-inducible factor-1 induced by hypoxia signal in a hypoxic state, further regulates the generation of hypoxia-inducible factor-1, and participates in the respiratory chain process of skin cells, thereby achieving precise induction activation of damaged and aged cells.
4. A hypoxia-inducible method for targeted anti-aging repair according to claim 3, wherein the hypoxia-inducible regulatory factor activates cellular respiration, can regulate genes acting on cellular respiratory chain, inhibits mitochondrial peroxidation, and protects the integrity of biofilm structure and lipid barrier.
5. A hypoxia-inducible method for targeted anti-aging therapy according to any one of claims 1 to 4, wherein the hypoxia-inducible regulatory factor is a developable component having functions of sensing hypoxia signals and regulating cell respiration, and is selected from one or more of plant extracts, animal extracts, microbial extracts, and fat-soluble quinones.
6. A hypoxia-inducible method for targeted anti-aging repair according to claim 1, wherein the antioxidant factor combines with free radicals or reactive oxygen species to form a stable low energy state, blocking chain reaction of liposome free radicals, preventing cell damage due to excessive oxidation.
7. A hypoxia-inducible method for targeted anti-aging repair according to claim 6, wherein the antioxidant factor acts on cell telomerase to enhance the activity thereof and extend the length of telomeres on both sides of chromosome, thereby achieving cell injury repair.
8. The hypoxia-inducible method for targeted anti-aging repair according to claim 6 or 7, wherein the antioxidant factor is a developable ingredient having an antioxidant free radical effect, and is selected from one or more of plant extract, animal extract, microbial extract, vitamins, peptides, phenols and enzymes.
9. A hypoxia-inducible method for targeted anti-aging repair according to claim 1, wherein the liposome pellets are further encapsulated with a cell activity-promoting factor.
10. A hypoxia-inducible method for targeted anti-aging repair according to claim 1, wherein the liposome beads are further encapsulated with a tissue repair factor.
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