CN107375005B - Polypeptide composition with antioxidation and melanin synthesis inhibition functions and application thereof - Google Patents
Polypeptide composition with antioxidation and melanin synthesis inhibition functions and application thereof Download PDFInfo
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- 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
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- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
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- 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
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- A—HUMAN NECESSITIES
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- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
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Abstract
The invention provides a polypeptide composition, which comprises one or more polypeptides with antioxidation and a combination of one or more polypeptides with melanin generation inhibition, wherein the mass concentration of each polypeptide component is 0.0001-5%. The composition is mainly used for improving/preventing skin aging and skin dark yellow caused by oxidation, thereby achieving the purpose of improving skin pigmentation, removing dark yellow and brightening skin color, and preventing various skin diseases caused by oxidative damage, such as lupus erythematosus, polymorphous light eruption, etc.
Description
Technical Field
The invention belongs to the field of medical cosmetics, and discloses a preparation method of a skin care product, which is characterized in that polypeptide with an antioxidant effect and polypeptide for inhibiting melanin are combined according to a formula, and various dosage forms including cream, essence, emulsion, freeze-dried powder and the like are prepared by adopting a method for compounding active polypeptide, and the skin care product is used for improving skin aging and dark yellow caused by oxidative stress, repairing oxidative damage of skin, brightening skin color and preventing various skin diseases such as lupus erythematosus, polymorphous light eruption and the like.
Background
The following description contains background information that may be useful for understanding the present invention, but is not an admission that any of the information provided herein is prior art to the presently claimed invention or related applications, nor is it an admission that any of the prior art specifically or implicitly referenced is prior art.
Skin is the tissue that reflects the aging of the body at the earliest time, and has attracted many scholars' interest in the study of skin wrinkles, elasticity, and skin moisture content. Skin aging is a very complex phenomenon involving a series of biological changes, such as changes in skin tissue cells, genes, and the immune system, as a result of the combined action of various factors (nutrition, environmental pollution, mental factors, mood changes, solar radiation, etc.) in and out of the body. According to the research of aging by researchers from various angles and research methods, many theories on aging including the theory of aging genes, the theory of telomere shortening, the theory of free radicals, the theory of immune function degeneration, etc. are summarized, wherein the theory of oxygen radicals is considered by the public to be closely related to aging. In 1956, Haman first proposed the theory of free radical metabolism for senescence, which was thought to be the result of cumulative oxidative damage to cellular components.
Oxidative Stress (OS) refers to that when Reactive Oxygen Species (ROS) are excessively produced or metabolically disturbed and exceed the ability of endogenous antioxidant defense systems to clear the ROS under harmful stimuli, the ROS are increased in vivo and participate in the formation of oxidized biomacromolecules, and directly or indirectly oxidize or damage DNA, proteins and lipids, which finally result in oxidative damage of cells, and is shown in the following aspects:
first, oxidative damage of cells in skin. Keratinocytes (KC) are the target of medium-wave ultraviolet radiation, and after ultraviolet radiation, intracellular inflammatory signaling mechanisms are activated and participate in immune and inflammatory responses of the body by expressing or secreting a series of inflammatory cytokines such as interleukin-1 (IL-1). In addition, uv light can also cause KC apoptosis, probably as direct DNA damage, induction of ROS formation and activation of cell membrane surface death receptors. Melanocytes (melanocytes) are located in the epidermis and have important significance for maintaining the skin's ability to withstand ultraviolet radiation, and form changes such as increase in the number of dendrites and cell swelling occur after irradiation with ultraviolet rays. Fibroblasts (fibroplasts) are the main sites for synthesizing collagen and elastic fibers, are located in the dermis layer of the skin, and are easily damaged by oxidation. It is induced by UV light to undergo apoptosis, as is KC.
And all the components in the cells including protein can be damaged by oxidation. The increase of oxygen free radicals in the skin produces a series of reactions: the excessive increase of oxygen free radicals in the body can attack cell membranes, proteins and nucleic acids to cause oxidative damage, and accelerate the skin epidermal aging. The main manifestation is that oxygen free radicals react with polyunsaturated fatty acid (PUFA) which is a main component on cell membranes to generate lipid peroxide free radicals and Lipid Peroxide (LPO), the membrane fluidity can be changed by the generated malondialdehyde through decomposition, and the lipid peroxide free radicals further accelerate the peroxidation of PUFA, so that the molecular rearrangement and crosslinking among PUFA are caused, the cell membrane fluidity is reduced, and the membrane operation is dysfunctional; oxygen free radicals can react with bases to aggregate DNA chains, lipid peroxide olefine aldehyde reacts with nucleic acid to break DNA alkanisation, so that gene change, gene mutation and normal function loss are caused to age; after the oxygen free radicals attack fibroblasts, the metabolism of collagen is abnormal, the synthesis of the collagen is reduced, abnormal cross-linking occurs, the structure of dermis is further influenced, and skin aging is accelerated. The oxidation-damaged proteins are generally degraded by proteases as main substances, and the defense function of proteases is gradually decreased due to aging, and the oxidation-damaged proteins are accumulated in the body. Furthermore, the intracellular accumulation of lipofuscin also interferes with the function of proteases. Cumulative damage to cellular components can lead to further disorganization of organ and tissue function, leading to further aging of the body.
And the skin color turns yellow and dark. The reason for yellowing of skin color is related to melanin, heme, carotenoid and Advanced Glycation End products AGEs (Advanced Glycation End-products), and the carbonylation of collagen and elastin in the dermis can also affect the yellowing of skin color. It has been reported that amino acids in protein molecules in the dermis (e.g., collagen fibers and elastic fibers) are susceptible to non-enzymatic glycosylation reactions with the aldehyde or ketone groups of reducing sugars to produce mature glycosylation end products (AGEs). AGEs progressively increase, and yellow-brown deposits of AGEs accumulate in the dermis, causing the skin to yellow. The carbonylation of collagen and elastin causes a gradual accumulation of lipofuscin, which also causes the skin to yellow and dull. The brown degenerative tissue changes caused by carbohydrates and proteins are commonly referred to as age spots. In addition, AGEs in the skin form intermolecular cross-linking of collagen fibers with age, which not only reduces permeability of connective tissues, weakens diffusivity of nutrients and wastes, increases extensibility and hardness of tissues, but also reduces solubility of collagen, so that collagen is difficult to hydrolyze by collagenase, thus reducing elasticity of the skin, preventing wrinkles from being smoothed and deepened, and promoting aging of the skin. Ultraviolet-induced skin aging may be associated with the accumulation of AGEs in the dermis, and studies have confirmed the hypothesis that non-enzymatically glycosylated proteins are photoreceptors of ultraviolet peroxidation damage in skin cells in vivo in the ultraviolet-induced skin peroxidation reaction of photoaged skin (Wondrak G T, et al, photosensified growth inhibition of cultured human skin cells and suppression of oxidative stress from systemic irradiation of secreted proteins, 2002,119: 489-498).
Ultraviolet rays have become a more and more major cause of oxidative damage to the skin. Ultraviolet B can directly interact with DNA of skin cells, and ultraviolet a mainly changes nuclear DNA and mitochondrial DNA by generating oxygen radicals harmful to the human body and activates Matrix Metalloproteinases (MMPs) to damage extracellular matrix. The MMPs mainly degrade skin cytoplasm matrix components such as collagen and elastin to thin the dermis layer of the skin. Thus, oxidative damage is always accompanied by aging and causes various problems of the skin, such as yellowing and dullness of the skin color. If the oxidative damage is further developed, skin diseases such as polymorphous light eruption are also produced, which is one of the most common photosensitive diseases, and the onset of the diseases can be related to ROS (free radicals such as hydroperoxide, singlet oxygen, superoxide anion and the like) commonly found in the skin; other diseases such as lupus erythematosus, vitiligo, psoriasis, etc., the onset of which may also be associated with ROS-induced cell tissue damage.
Dark skin color has another factor besides the oxidative damage factor, namely that the melanin cells are stimulated to generate melanin under the irradiation of ultraviolet rays, and the deposition of the melanin has great influence on the skin color, so that the skin color is deepened, and spots are generated. As also stated above, melanocytes are of great importance for the resistance of the skin to uv light, and the melanin produced absorbs harmful uv radiation so that damage caused by uv-induced free radicals is minimized. However, melanocytes are damaged by oxidative stress for a long time, and the mechanism of damage is not known.
In combination with the above, it is very necessary to develop products with antioxidant and melanin production inhibiting effects, to remove free radicals from the skin, delay skin aging, remove dark yellow, improve skin color, and prevent various skin diseases.
Disclosure of Invention
In order to solve the above skin problems, the present invention provides a polypeptide composition, comprising:
(1) one or more polypeptides with antioxidant reaction and free radical scavenging effects selected from carnosine, glutathione, acetyl carnosine, palmitoyl carnosine, and decarboxylated carnosine;
and
(2) one or more polypeptides having a melanogenesis inhibitory activity, selected from Nonapeptide-1 (L-methionyl-L-prolyl-D-phenylalanyl-L-arginyl-D-tryptophanyl-L-phenylalanyl-L-lysyl-L-prolyl-L-valinamide) CAS:158563-45-2), tetrapeptide-27(Lightenin, Tetrapeptide-27(Tego-pep-4Even)), Decapeptide-12 (Decapetide-12 (Lumixyl)TMEnvy Medical, Inc., Westlake Village, USA)), Hexapeptide-2 (Dexameptide-2 (Dermostatyl)TMIS));
Wherein the mass concentration of each polypeptide component is 0.0001-5%.
The polypeptide composition of the invention can be a combination of two peptides, carnosine and nonapeptide-1 or a combination of two peptides, carnosine and tetrapeptide-27.
The polypeptide composition of the invention can also be a combination of three peptides, namely carnosine and nonapeptide-1 and tetrapeptide-27 or a combination of three peptides, namely carnosine, acetyl carnosine and nonapeptide-1.
The polypeptide composition of the invention can also be a combination of four peptides, namely carnosine, glutathione and nonapeptide-1 and tetrapeptide-27 or a combination of four peptides, namely carnosine and nonapeptide-1, tetrapeptide-27 and decapeptide-12.
The polypeptide composition of the invention can be added with other components with antioxidant effect, such as ascorbic acid (vitamin C), vitamin E, blumea balsamifera oil, and the like.
The composition of the present invention is for topical application to the skin and may include humectants such as hyaluronic acid, aloe vera gel, glycerin, and the like. Because healthy skin is weakly acidic, the preferred pH of the skin care product is 5.0-7.0, and thus the composition requires pH adjustment, the pH adjusting agent is preferably triethanolamine.
In order to prevent the pollution of the external environment and the invasion of bacteria, the composition of the invention can be added with some preservatives, preferably caprylyl glycol; or an antibacterial substance, preferably 1, 2-hexanediol.
The polypeptide composition can be prepared into various dosage forms, such as the development product dosage forms mainly comprise essence, powder (capsules and freeze-dried powder), emulsion, cream, gel, facial mask, dressing and the like; the product can be facial mask, moisturizing essence, lotion, medical dressing, etc.
The polypeptide compositions of the present invention can be topically applied to the skin to prevent aging, wrinkles, dark skin tone resulting from oxidative damage to the skin, dark spots resulting from melanin pigmentation, and any combination of skin problems.
The polypeptide compositions of the present invention may also be used to improve dark yellow skin, hyperpigmentation, chloasma, wrinkles, oxidative inflammation and any combination of skin conditions.
The invention has the advantages that:
the research and exploration of the polypeptide in the skin field by the inventor have been experienced for many years, and the action mechanism of the polypeptide on skin care is clear and has better safety. Polypeptides are compounds in which amino acid residues are linked by peptide bonds. Depending on the number of different amino acid residues and the type of amino acid residues in the peptide chain, various polypeptides can be formed, but their mechanism of action differs. Like the inhibitory pathway of a polypeptide for melanin, different polypeptides may have a less similar pathway of action: nonapeptide-1 (composed of nine amino acid residues) (Pooja Bains, Topical peptides for administration: potential role in biology 2016, 5:118-125) and hexapeptide-2 (composed of six amino acid residues) are used as MC1-R antagonists to inhibit the activation of melanocytes to achieve the effect of inhibiting melanin; decapeptide-12 (composed of ten amino acid residues) is used as a tyrosinase inhibitor in melanocytes, and can inhibit the production of melanin by inhibiting the activity of tyrosinase (Andrea t. kassim, et al, Open-label evaluation of the skin-drying efficiency of skin-drying system using decapeptide-12, 2012,14: 117-121). The peptides inhibit the generation of melanin from different action sites, particularly the nonapeptide-1 is also called whitening nonapeptide and is widely applied to whitening and freckle removing products on the market. Carnosine is a polypeptide consisting of two amino acid residues, and has a better protective effect on oxidative damage of skin under certain conditions: has good inhibiting effect on the formation of AGE; scavenging free Radicals (ROS) produced and end products produced by ROS-induced lipid peroxidation, particularly HNE, which can attack and mutate the nucleotide bases of NDA; can effectively slow down the DNA damage caused by ROS (Reddy VP, et al, Carbosine: A Versatile antibiotic and neutralizing Agent, 2005). In recent years, carnosine has also been widely added to skin care products.
At present, the emphasis of the polypeptide products for brightening skin color on inhibiting the generation of skin melanin or resisting oxidation is single in effect in the market. The invention innovatively provides that the polypeptide with the antioxidation (such as carnosine) and the polypeptide for inhibiting the generation of melanin (such as nonapeptide-1) are combined together from the microstructure of the skin and the action mechanism of the physiological change of the skin, so that the skin aging can be effectively prevented, the skin color is lightened, and the invention has better effect and shows better synergistic effect compared with the single use.
Drawings
FIG. 1 is a graph showing the effect of the polypeptides of examples 1 to 4 on skin color.
FIG. 2 is a graph showing the effect of the polypeptides of example 1 and comparative examples 1-2 on skin color.
Detailed Description
For a better understanding of the present invention, the following detailed description is given in conjunction with the following examples and drawings, but is not limited to the following examples.
EXAMPLE 1 preparation of polypeptide composition solution (antioxidant essence)
The polypeptide composition of the present invention was prepared as a serum according to the following polypeptide solution recipe.
Solution recipe (1 kg essence):
the configuration method comprises the following steps:
adding the sodium hyaluronate into water according to the formula ratio, stirring to uniformly mix, heating to 80-85 ℃, and keeping the temperature and stirring to uniformly disperse the sodium hyaluronate. Cooling to below 40 deg.C, adding glycerol, aloe gel, carnosine, nonapeptide-1, vitamin C, sodium hyaluronate, caprylyl glycol and 1, 2-hexanediol, and stirring. The pH of the solution was adjusted to about 5.5 with 15% triethanolamine.
Example 2
Solution recipe (1 kg essence):
the configuration method comprises the following steps:
adding the sodium hyaluronate into water according to the formula ratio, stirring to uniformly mix, heating to 80-85 ℃, and keeping the temperature and stirring to uniformly disperse the sodium hyaluronate. Cooling to below 40 deg.C, adding glycerol, aloe gel, carnosine, tetrapeptide-27, vitamin C, sodium hyaluronate, caprylyl glycol and 1, 2-hexanediol, and stirring. The pH of the solution was adjusted to about 5.5 with 15% triethanolamine.
Example 3
Solution recipe (1 kg essence):
the configuration method comprises the following steps:
adding the sodium hyaluronate into water according to the formula ratio, stirring to uniformly mix, heating to 80-85 ℃, and keeping the temperature and stirring to uniformly disperse the sodium hyaluronate. Cooling to below 40 deg.C, adding glycerol, aloe gel, carnosine, nonapeptide-1, acetyl carnosine, vitamin C, sodium hyaluronate, caprylyl glycol and 1, 2-hexanediol, and stirring. The pH of the solution was adjusted to about 5.5 with 15% triethanolamine.
Example 4
Solution recipe (1 kg essence):
the configuration method comprises the following steps:
adding the sodium hyaluronate into water according to the formula ratio, stirring to uniformly mix, heating to 80-85 ℃, and keeping the temperature and stirring to uniformly disperse the sodium hyaluronate. Cooling to below 40 deg.C, adding glycerol, Aloe gel, carnosine, nonapeptide-1, glutathione, tetrapeptide-27, vitamin C, sodium hyaluronate, caprylyl glycol and 1, 2-hexanediol, and stirring. The pH of the solution was adjusted to about 5.5 with 15% triethanolamine.
Comparative example 1 preparation of polypeptide solution (antioxidant essence)
Serum was prepared according to the solution formulation of example 1 except that nonapeptide-1 was not contained and deionized water was substituted.
Solution recipe (1 kg essence):
the configuration method comprises the following steps:
adding the sodium hyaluronate into water according to the formula ratio, stirring to uniformly mix, heating to 80-85 ℃, and keeping the temperature and stirring to uniformly disperse the sodium hyaluronate. Cooling to below 40 deg.C, adding glycerol, aloe gel, carnosine, vitamin C, sodium hyaluronate, caprylyl glycol and 1, 2-hexanediol, and stirring. The pH of the solution was adjusted to about 5.5 with 15% triethanolamine.
Comparative example 2
Serum was prepared according to the solution formulation of example 1 except that carnosine was not included and deionized water was substituted.
Solution recipe (1 kg essence):
the configuration method comprises the following steps:
adding the sodium hyaluronate into water according to the formula ratio, stirring to uniformly mix, heating to 80-85 ℃, and keeping the temperature and stirring to uniformly disperse the sodium hyaluronate. Cooling to below 40 deg.C, adding glycerol, Aloe gel, nonapeptide-1, vitamin C, sodium hyaluronate, caprylyl glycol and 1, 2-hexanediol, and stirring. The pH of the solution was adjusted to about 5.5 with 15% triethanolamine.
Example 5 test study for improving skin complexion
Healthy volunteers between 18-55 ages and with dark yellow facial skin and marked mottle were selected and randomized into six groups of 30 individuals, four of which were treated with the products of example 1, example 2, example 3 and example 4, respectively, and two of which were treated with the products of comparative example 1 and comparative example 2, respectively, for 8 weeks. During the test, the volunteers were unable to change the original facial cleansing style and habits, except that, in addition, no other cosmetic than the test product could be used. Before using the product, after using the product for 4 weeks and 8 weeks, the cheeks were subjected to a skin color test, respectively, to observe the improvement of the product on the skin's dark yellow color and the color spots.
The skin color was measured using a colorimeter (CR-400, Konica Minolta, Japan) in the test. The instrument uses the color system (Lab color system) specified by the International Commission on illumination (CIE) to show the change in skin color. Wherein:
l is brightness, a is red-green chroma, b is blue-yellow chroma, and the comprehensive evaluation of the three can reflect the change of skin chroma; the ITA ° values are skin individual type angles and are values related to L and b that characterize skin brightness. The greater the ITA value, the brighter the skin, whereas the darker the skin.
The test area for the skin color test (Chromameter) was the left and right cheek, and 3 tests were averaged for each test area. The results are shown in FIGS. 1 and 2.
The experimental result shows that the polypeptide can improve the skin chromaticity, and the effect is more obvious when the polypeptide is used for a longer time; the combined use effect of the carnosine and the nonapeptide-1 is better than that of single carnosine or single nonapeptide-1, and the side deduces that different types of peptides are combined for use and can act together from different targets, thereby achieving the effects of improving pigmentation, brightening skin color, removing freckles and eliminating dark yellow and having good synergistic effect.
The foregoing is a more detailed description of the present invention in connection with specific preferred embodiments thereof, and is not intended to limit the invention to the particular forms disclosed. It will be apparent to those skilled in the art that a number of simple derivations or substitutions can be made without departing from the inventive concept. The above description is only exemplary of the present invention and should not be taken as limiting the invention, as any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A polypeptide composition characterized by comprising:
carnosine, nonapeptide-1, vitamin C, sodium hyaluronate, glycerol, aloe vera gel, caprylyl glycol, 1, 2-hexanediol, triethanolamine and deionized water; wherein the mass percentage concentration of the nonapeptide-1 is 0.0001-5%, the content of the carnosine is 0.2-0.4%, and the content ratio of the carnosine to the nonapeptide-1 is 40: 1.
2. The composition of claim 1, wherein said polypeptide composition further comprises an acetyl carnosine or glutathione.
3. The composition of claim 1, wherein said polypeptide composition further comprises tetrapeptide-27.
4. The composition of claim 1, wherein the components of said polypeptide composition, carnosine, nonapeptide-1, vitamin C, sodium hyaluronate, glycerol, aloe vera gel, caprylyl glycol, 1, 2-hexanediol, triethanolamine, and deionized water, are present in amounts of 0.4%, 0.01%, 0.005%, 0.4%, 5%, 0.25%, 0.04%, and the balance, respectively.
5. The composition of claim 2, wherein said acetyl carnosine or glutathione is present in an amount of 0.1%.
6. The composition of claim 3, wherein said tetrapeptide-27 is present in an amount of 0.0007%.
7. The composition of any one of claims 1-6, wherein the polypeptide composition has a pH in the range of 3.0 to 8.0.
8. The composition of any one of claims 1 to 6, wherein the composition is in the form of a serum, powder, capsule, emulsion, cream, gel, mask or dressing.
9. Use of a composition according to any one of claims 1 to 8 for the preparation of a cosmetic product or a medicament for the treatment and/or care of the skin, wherein the cosmetic product or medicament is in a form selected from the group consisting of a mask, a moisturizing essence, a lotion, an eye cream, a skin external form for medical dressings.
10. Use of a composition according to claim 9 for preventing skin aging due to oxidative damage, wrinkles, dark skin tone resulting from melanin pigmentation, dark spots and skin problems in any combination; or for improving skin dark yellow, hyperpigmentation, pigmented spots, wrinkles, oxidative inflammation and any combination of skin conditions.
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