CN113545998A - Hydroxyapatite and collagen composition and application thereof in removing nevus, removing freckles, reducing pigmentation and whitening - Google Patents

Hydroxyapatite and collagen composition and application thereof in removing nevus, removing freckles, reducing pigmentation and whitening Download PDF

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CN113545998A
CN113545998A CN202010334319.3A CN202010334319A CN113545998A CN 113545998 A CN113545998 A CN 113545998A CN 202010334319 A CN202010334319 A CN 202010334319A CN 113545998 A CN113545998 A CN 113545998A
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hydroxyapatite
collagen
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nevus
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CN113545998B (en
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马驰
廖兴
王芳
黄新凡
罗平
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Shanghai Ruixing Medical Equipment Co ltd
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Abstract

The invention provides a hydroxyapatite and collagen composition and application thereof in removing nevus and freckles, reducing pigmentation and whitening. In particular, the composition or formulation or product is for: (a) removing moles and/or bland moles; (b) spot removal and/or lightening; and/or (c) reducing pigmentation and/or whitening; wherein, the active ingredients comprise: (Y1) first active ingredient: hydroxyapatite. The composition of the invention has good safety and high effectiveness.

Description

Hydroxyapatite and collagen composition and application thereof in removing nevus, removing freckles, reducing pigmentation and whitening
Technical Field
The present invention relates to the fields of medicine, medical equipment and cosmetics. In particular to application of hydroxyapatite composite collagen in removing nevus/lightening nevus, removing freckles/lightening spots, reducing pigmentation and whitening, and a composition and a preparation based on the hydroxyapatite composite collagen.
Background
With the continuous improvement of living standard and medical standard, the recovery of skin form is not only for the purpose of recovering the function alone, but also more importantly, for meeting aesthetic requirements and improving the living quality. The treatment and prevention of pigmented spots and nevi has been a major medical problem, especially the incidence of photoaging skin pigmentation spots above 30 years old, age spots, solar keratoses, post-acne pigmentation spots, freckles, lentigo, various kinds and pigmented nevi is very high, and they are generated, increased, enlarged with increasing age or pathological causes, and are difficult to eliminate.
At present, the treatment methods for pigmented spots and melanin nevus mainly comprise laser, microwave, fulgerizing, freezing, chemical skin changing, grinding and the like, and the common characteristics of the treatment methods are that the pigmented spots are removed by physical or chemical methods, but the methods have high cost, high recurrence rate and safety. If the chemical medicine is usually corrosive, long-term pigmentation or pigment loss, even scar, disfigurement, etc. are likely to occur when the chemical medicine is improperly used.
There is therefore a need in the art to provide products that safely remove/lighten moles, spots/patches, reduce pigmentation, and whiten skin.
Disclosure of Invention
The invention aims to provide a product capable of safely removing/lightening nevus, removing/lightening spots, reducing pigmentation and whitening.
In a first aspect of the invention, there is provided the use of an active ingredient for the manufacture of a composition or formulation or product for: (a) removing moles and/or bland moles; (b) spot removal and/or lightening; and/or (c) reducing pigmentation and/or whitening;
wherein, the active ingredients comprise: (Y1) first active ingredient: hydroxyapatite.
In another preferred embodiment, the active ingredients comprise: (Y1) first active ingredient: hydroxyapatite; and (Y2) a second active ingredient: collagen protein.
In another preferred embodiment, the mass ratio of the first active ingredient to the second active ingredient is 1:10 to 10:1, preferably 1: 5-5:1, preferably 1:2-2: 1.
In another preferred embodiment, the composition comprises:
(Y1) first active ingredient: hydroxyapatite;
(Y2) second active ingredient: collagen protein; and
(Z) a pharmaceutically or cosmetically acceptable carrier.
In another preferred embodiment, the composition is a pharmaceutical composition or a cosmetic composition.
In another preferred embodiment, the dosage form of the composition is selected from the group consisting of: solid, semi-solid, or liquid dosage forms, such as solutions, gels, creams, lotions, ointments, creams, pastes, cakes, powders, patches, and the like.
In another preferred embodiment, the product is selected from the group consisting of: lotion, cream, lotion, sunscreen agent, facial mask, facial cleanser, essence, foundation make-up, white powder, blush, and soap.
In another preferred embodiment, the nevus is selected from the group consisting of: congenital melanocytic nevus, lentigo, sebaceous gland nevus, nevus cell nevus, pigmented nevus, melanocytic nevus, acquired melanocytic nevus, or combinations thereof
In another preferred embodiment, the spot is selected from the group consisting of: chloasma, black speck, freckle, senile plaque, or their combination.
In another preferred embodiment, the pigmentation is selected from the group consisting of: black pigmentation after sun (photoaging), scar causing black pigmentation, post acne pigmentation, or combinations thereof.
In another preferred embodiment, the whitening is selected from the group consisting of: increase skin brightness, improve uneven skin tone, or a combination thereof.
In a second aspect of the present invention, there is provided a composition comprising:
(Y1) first active ingredient: hydroxyapatite;
(Y2) second active ingredient: collagen protein; and
(Z) a pharmaceutically or cosmetically acceptable carrier.
In another preferred embodiment, the hydroxyapatite is selected from the group consisting of: ceramic hydroxyapatite, non-ceramic hydroxyapatite, amorphous hydroxyapatite, calcium deficient hydroxyapatite, amorphous hydroxyapatite, a mixture of hydroxyapatite and calcium phosphate, or a combination thereof; preferably, the calcium deficient hydroxyapatite.
In another preferred embodiment, the mass ratio of the first active ingredient to the second active ingredient is 1:10 to 10:1, preferably 1: 5-5:1, preferably 1:2-2: 1.
In another preferred embodiment, the hydroxyapatite has a calcium to phosphorus molar ratio < 1.67, preferably 1.5 to 1.67, 1.53 to 1.65 or 1.55 to 1.62.
In another preferred embodiment, for example, the collagen has a molecular weight of 6000Da or less, preferably 5000Da or less, 3000Da or less, 2000Da or less, or 1000Da or less, preferably 200Da or less.
In another preferred embodiment, the hydroxyapatite is in a form selected from the group consisting of: needle, rod, sphere, or combinations thereof, preferably needle or rod.
In another preferred embodiment, the hydroxyapatite has a size of 0.5nm to 950 μm, preferably 1nm to 100 μm, 2nm to 10 μm, 5nm to 2 μm or 10nm to 1 μm, 20nm to 500 nm.
In another preferred embodiment, the collagen is selected from the group consisting of: human collagen, bovine collagen, porcine collagen, fish collagen, donkey collagen, or combinations thereof; preferably, fish collagen.
In another preferred embodiment, the collagen is natural collagen or recombinant collagen.
In another preferred embodiment, the collagen content of the composition is 1-10 wt%, preferably 3-9 wt%, more preferably 4-7 wt%.
In another preferred embodiment, the content of hydroxyapatite in the composition is 1 to 20 wt%, preferably 2 to 15 wt%, more preferably 3 to 12 wt% or 4 to 9 wt%.
In another preferred embodiment, the sum of the first active ingredient and the second active ingredient in the composition is 0.1 to 95 wt%, preferably 0.5 to 80 wt%, 1 to 60 wt%, 2 to 50 wt%, 4 to 30 wt% or 5 to 25 wt%.
In another preferred embodiment, the composition is a pharmaceutical composition or a cosmetic composition.
In another preferred embodiment, the composition further comprises an additional component selected from the group consisting of: an anti-inflammatory component, an antioxidant component, an anti-ultraviolet component, or a combination thereof.
In another preferred embodiment, the cosmetically acceptable carrier or excipient is selected from the group consisting of: humectant, antioxidant, anti-ultraviolet agent, antiseptic, film forming agent, oil soluble gelling agent, organic modified clay mineral, resin, antibacterial agent, essence, salt, pH regulator, chelating agent, algefacient, antiinflammatory agent, skin beautifying component, vitamin, amino acid, nucleic acid, hormone, inclusion compound or their combination.
It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be reiterated herein, but to the extent of space.
Drawings
FIG. 1 shows the effect of different ratios of HAP and collagen on melanin synthesis in B16 melanoma cells when used in combination;
FIG. 2 shows the effect of a composition of the invention on the reduction/removal of moles;
FIG. 3 shows the effect of one embodiment of the composition of the present invention to lighten/remove spots, reduce pigmentation;
Detailed Description
The present inventors have extensively and deeply studied and, through a large number of screening and testing, provided a composition comprising hydroxyapatite and collagen, and found that hydroxyapatite has excellent effects of removing nevi, removing freckles and whitening, and surprisingly, hydroxyapatite and collagen have significant synergistic effects in the relevant aspects of removing nevi, removing freckles and whitening. The present invention has been completed based on this finding.
Term(s) for
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.
As used herein, the term "about" when used in reference to a specifically recited value means that the value may vary by no more than 1% from the recited value. For example, as used herein, the expression "about 100" includes 99 and 101 and all values in between (e.g., 99.1, 99.2, 99.3, 99.4, etc.).
As used herein, the term "comprising" or "includes" can be open, semi-closed, and closed. In other words, the term also includes "consisting essentially of …," or "consisting of ….
The term "room temperature" as used herein means a temperature of 4-40 ℃, preferably 25 ± 5 ℃.
Hydroxyapatite
Hydroxyapatite (HAP), also known as Hydroxyapatite, basic calcium phosphate, is calcium apatite Ca5(PO4)3Naturally mineralized OH. The theoretical composition of hydroxyapatite is Ca10(PO4)6(OH)2The calcium to phosphorus ratio (Ca/P) is about 1.67, but the actual composition may not be stoichiometrically formed.
Hydroxyapatite is the main inorganic component of human skeletal tissue, and after being implanted into the body, calcium and phosphorus can be dissociated from the surface of the material and absorbed by the body tissue, and new tissues can grow. Therefore, the hydroxyapatite is a biological inorganic material with excellent performance, has good biocompatibility and chemical stability, and does not produce irritation and corrosion to the skin.
In the present invention, the source and crystallization method of the hydroxyapatite are not particularly required, and various forms of hydroxyapatite derived from various sources can be used. Such as natural hydroxyapatite or synthetic hydroxyapatite. Methods for preparing the hydroxyapatite are known in the art.
Preferably, the hydroxyapatite is selected from the group consisting of: ceramic hydroxyapatite, non-ceramic hydroxyapatite, amorphous hydroxyapatite, calcium deficient hydroxyapatite, amorphous hydroxyapatite, a mixture of hydroxyapatite and calcium phosphate, or a combination thereof; preferably, the calcium deficient hydroxyapatite.
Preferably, the hydroxyapatite is a calcium deficient apatite, e.g. the hydroxyapatite has a calcium to phosphorus molar ratio < 1.67, preferably 1.5-1.67, 1.53-1.65 or 1.55-1.62.
The hydroxyapatite in the present invention may be present in any suitable form, such as needle, rod, sphere.
The size of the hydroxyapatite can be selected according to requirements. The size of the hydroxyapatite is 1nm-100 μm, 2nm-10 μm, 5nm-2 μm or 10nm-1 μm, 20nm-500nm, and the size is calculated by the length of the maximum position.
Collagen protein
As used herein, the terms "collagen" and "collagen peptide" are used interchangeably and include collagen from natural sources and also collagen prepared by genetic recombination methods, including intact collagen as well as collagen hydrolysates.
Typically, the collagen includes, but is not limited to: human collagen, bovine collagen, porcine collagen, fish collagen, donkey collagen, or combinations thereof; preferably, fish collagen.
Preferably, the collagen is a collagen peptide, more preferably, an oligopeptide.
Preferably, for example, the collagen has a molecular weight of 6000Da or less, preferably 5000Da or less, 3000Da or less, 2000Da or less, or 1000Da or less, preferably 200Da or less.
Composition comprising a metal oxide and a metal oxide
The present invention provides a composition comprising:
(Y1) first active ingredient: hydroxyapatite;
(Y2) second active ingredient: collagen protein; and
(Z) a pharmaceutically or cosmetically acceptable carrier.
In another preferred embodiment, the mass ratio of the first active ingredient to the second active ingredient is 1:10 to 10:1, preferably 1: 5-5:1, preferably 1:2-2: 1.
In another preferred embodiment, the sum of the first active ingredient and the second active ingredient in the composition is 0.1 to 95 wt%, preferably 0.5 to 80 wt%, 1 to 60 wt%, 2 to 50 wt%, 4 to 30 wt% or 5 to 25 wt%. For cost performance reasons, the composition is best when the first active ingredient is 3-6 wt% and the second active ingredient is 3-6 wt%.
Applications of
The invention provides hydroxyapatite, a combination of hydroxyapatite and collagen, and uses of the composition, for (a) removing moles and/or lightening moles; (b) spot removal and/or lightening; and/or (c) reducing pigmentation and/or whitening.
Experiments prove that the combination of hydroxyapatite, hydroxyapatite and collagen can reduce the generation and deposition of melanin by cells; after melanin is generated and deposited, the skin problems of nevus, spots and the like formed by melanin can be effectively removed, and the whitening effect is achieved.
In the present invention, the term "nevus" refers to skin manifestations caused by epidermal and intradermal melanocyte proliferation, including congenital melanocyte nevus, acquired melanocyte nevus, sebaceous gland nevus and other types of nevus, especially pigmented nevus. Such nevi include, but are not limited to: a congenital melanocytic nevus, lentigo, sebaceous gland nevus, a nevus cell nevus, a pigmented nevus, a melanocytic nevus, an acquired melanocytic nevus, or a combination thereof.
In the present invention, the term "spots" refers to spots, especially pigmented spots, which are different in color from the surrounding skin. The plaque includes but is not limited to: chloasma, dark spots, freckles, age spots, or combinations thereof.
Preferably, the pigmentation is selected from the group consisting of: black pigmentation after sun (photoaging), scar causing melanin pigmentation, post acne pigmentation, or combinations thereof.
In the present invention, the term "whitening" includes increasing skin brightness and improving uneven skin color.
In the present invention, hydroxyapatite or a combination of hydroxyapatite and collagen may be prepared into a pharmaceutical composition or a cosmetic composition.
Possible pharmaceutical compositions are, for example, powders, microgranules, solutions, jellies, creams, suspensions, poultices, liniments, lotions and the like. The drug can be prepared by a generally known preparation technique, and a suitable pharmaceutically acceptable carrier can be added to the drug.
Examples of the pharmaceutically acceptable carrier include excipients, binders, disintegrating agents, lubricants, flow aids, suspending agents, emulsifiers, stabilizers, warming (wetting) agents, preservatives, solvents, solubilizers, preservatives, flavoring agents, sweeteners, dyes, flavors, propellants and the like, and these carriers can be selected and added in an appropriate amount within a range not affecting the effect of the present invention.
It is possible to prepare hydroxyapatite or a combination of hydroxyapatite and collagen into cosmetic compositions, such as dosage forms of emulsions, liquids, ointments, creams, pastes, cakes, powders, and the like.
Other ingredients used in general cosmetics, such as film-forming agents, oil-soluble gelling agents, organically modified clay minerals, resins, moisturizers, preservatives, antibacterial agents, perfumes, salts, antioxidants, pH adjusters, chelating agents, cooling agents, anti-inflammatory agents, skin beautifying ingredients (whitening agents, cell activators, skin roughness improvers, blood circulation improvers, skin astringents, anti-lipid leakage agents, and the like), vitamins, amino acids, nucleic acids, hormones, inclusion compounds, and the like may be added to the cosmetic of the present invention within a range that does not interfere with the effects of the present invention.
The oil-soluble gelling agent is selected from metal soaps such as aluminum stearate, magnesium stearate, and zinc myristate; amino acid derivatives such as N-lauroyl-L-glutamic acid, alpha, gamma-di-N-butylamine, and the like; cyclodextrin fatty acid esters such as cyclodextrin palmitate, cyclodextrin stearate, and cyclodextrin 2-ethylhexanoate palmitate; sucrose fatty acid esters such as sucrose palmitate and sucrose stearate; benzylidene derivatives of sorbitol such as monobenzylidene sorbitol and dibenzylidene sorbitol; one or two or more gelling agents such as an organically modified clay mineral such as dimethylbenzyldodecylammonium montmorillonite clay or dimethyloctacosylammonium montmorillonite clay may be used as necessary.
The humectant comprises: glycerin, sorbitol, propylene glycol, dipropylene glycol, 1, 3-butylene glycol, glucose, xylitol, maltitol, polyethylene glycol, hyaluronic acid, chondroitin sulfate, pyrrolidone carboxylate, polyoxyethylene methyl glucoside, polyoxypropylene methyl glucoside, and the like.
The antibacterial preservative comprises: alkyl parabens, benzoic acid, sodium benzoate, sorbic acid, potassium sorbate, phenoxyethanol, and the like, and antibacterial agents such as: benzoic acid, salicylic acid, carbolic acid, sorbic acid, alkyl parabens, parachloro-metacresol, hexachlorophene, benzalkonium chloride, chlorhexidine chloride, trichloro-carbanilide, triclosan, a photosensitizer, phenoxyethanol, and the like.
The antioxidant is as follows: tocopherol, butyl hydroxy anisole, dibutyl hydroxy toluene, phytic acid and the like, and pH regulators comprise: lactic acid, citric acid, glycolic acid, succinic acid, tartaric acid, dl-malic acid, potassium carbonate, sodium bicarbonate, ammonium bicarbonate, and the like, as chelating agents, alanine, sodium ethylenediaminetetraacetate, sodium polyphosphate, sodium metaphosphate, phosphoric acid, and the like, as cooling agents: l-menthol, camphor, etc., and the anti-inflammatory agents include: allantoin, glycyrrhetinic acid, glycyrrhizic acid, tranexamic acid, and Azulene (Azulene).
The skin beautifying components are as follows: whitening agent such as placenta extract, arbutin, glutathione, and herba Saxifragae extract; cell activator such as Lac Regis Apis, photosensitizer, cholesterol derivative, calf blood extractive solution, etc.; an agent for improving rough skin; blood circulation promoters such as valeriana nonanoate, benzyl nicotinate, beta-butoxyethyl nicotinate, capsaicin, zingerone, tincture of cantharides, ichthammol, caffeine, tannic acid, alpha-borneol, tocopherol nicotinate, inositol hexanicotinate, cyclamate, cinnarizine, tolazoline, acetylcholine, verapamil, cepharanthine, and gamma-oryzanol; skin astringents such as zinc oxide and tannic acid; sulfur, and antilipidemic agents, and the like, and vitamins include: vitamin A oil, rosin oil, acetic acid rosin oil, palmitic acid rosin oil, and the like; vitamin B2 such as riboflavin, riboflavin butyrate, and flavin adenine nucleotide; vitamin B6 such as pyridoxine hydrochloride, pyridoxine dicaprylate, and pyridoxine tripalmitate, vitamin B12 and its derivatives, and vitamin B15 and its derivatives; vitamin C compounds such as L-ascorbic acid, L-ascorbic acid dipalmitate, L-ascorbic acid-2-sodium sulfate, and L-ascorbic acid phosphoric acid diester dipotassium; vitamin D compounds such as ergocalciferol and cholecalciferol; vitamin E compounds such as alpha-tocopherol, beta-tocopherol, gamma-tocopherol, dl-alpha-tocopherol acetate, dl-alpha-tocopherol nicotinate, dl-alpha-tocopherol succinate, and the like; vitamin H; a vitamin P; nicotinic acids such as nicotinic acid, benzyl nicotinate and nicotinamide; pantothenic acids such as calcium pantothenate, D-panthenol, panthenyl ethyl ether, and acetyl panthenyl ethyl ether; biotin, and the like.
The amino acids are: glycine, valine, leucine, isoleucine, serine, threonine, phenylalanine, arginine, lysine, aspartic acid, glutamic acid, cystine, cysteine, methionine, tryptophan, etc., nucleic acids include deoxyribonucleic acid, etc., and hormones include estradiol, vinylestradiol, etc.
Preferred examples of the cosmetic of the present invention include: skin care cosmetics, makeup cosmetics, and ultraviolet-shielding cosmetics. Such as basic cosmetics such as milky lotion, cream, lotion, sunscreen agent, mask material, face toilet, essence, etc.; makeup cosmetics such as foundation, powdery, blush, and the like.
The form of the product is not particularly limited, and may be liquid, emulsion, cream, solid, paste, gel, powder, multilayer, mousse (mousse), spray, or the like.
The present invention also provides a skin care method, comprising the steps of: administering to an individual in need thereof hydroxyapatite, or a combination of hydroxyapatite and collagen, or a composition of the invention.
In another preferred embodiment, the method is (a) nevus removal and/or nevus pallidus; (b) spot removal and/or lightening; and/or (c) methods of reducing pigmentation and/or whitening.
In the present invention, the applications of reducing pigmentation, whitening and the like include both preventive and post-improvement applications. For example, for post-acne pigmentation, administration of an active ingredient or composition of the invention before, during, and/or after the appearance of acne is included to reduce pigmentation.
The main advantages of the invention include:
1. the hydroxyapatite is found to have the effects of removing nevus and/or lightening nevus, removing freckles and/or lightening spots, reducing pigmentation, whitening and the like and relieving pigment accumulation on the surface of the skin for the first time.
2. The hydroxyapatite and the collagen have obvious synergistic effects on removing nevus and/or lightening nevus, removing freckles and/or lightening spots, reducing pigmentation, whitening and the like.
3. The invention provides an effective, safe and noninvasive composition with the effects of removing nevus and/or lightening nevus, removing freckles and/or lightening spots, reducing pigmentation and/or whitening.
4. The composition of the invention has obviously improved healing effect on nevus and spots.
The invention is further illustrated with reference to specific embodiments. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out under conventional conditions or conditions recommended by the manufacturers. Unless otherwise indicated, percentages and parts are by weight.
HAP: calcium-deficient hydroxyapatite (calcium-phosphorus ratio: 1.59); a non-ceramic rod-like HAP with a diameter of 2-5 nm and a length of 100-500 nm;
collagen protein: fish collagen peptide, provided by Wuhan Yuancheng Co-creation science and technology Limited, meets the Q/HRB003S standard. Molecular weight (DAL) is less than or equal to 1000, pH value: 6.52, ash: 0.67%, protein (conversion factor 5.79): 99.2% (Dry basis).
Mouse B16 melanoma cell line: in RPMI1640 medium (containing 10% calf serum, 105U/L penicillin, 105U/L streptomycin), at 37 deg.C and 5% CO2Cultured in an incubator and subcultured every 3 days.
And (3) statistical treatment: SPSS11.0 software
Example 1
The effect of different ratios of HAP and collagen on melanin synthesis in B16 melanoma cells was investigated.
Determination of melanin content: taking B16 cells in logarithmic growth phase, digesting with 0.25% pancreatin, and adjusting cell concentration to 5 × 105/ml, inoculating into 6-well culture plate, adding 2ml cell suspension per well, standing at 37 deg.C and 5% CO2Culturing in an incubator. And after the cells adhere to the wall for 24 hours, removing the culture solution. In the experimental group, 2ml of the whole culture solution containing HAP and collagen was added at the concentrations shown in Table 1, and the total volume was 81.
TABLE 1
Figure BDA0002466052920000091
The blank was added with equal amount of complete medium. Each set of treatments was replicated in 6 wells. Adding 1mol/LNaOH containing 10% DMSO, ultrasonicating for 30min, placing in 90 deg.C water bath for 2h, and measuring absorbance (A) at 450 nm.
Relative melanin synthesis content%
TABLE 2 relative melanin content (%)
Figure BDA0002466052920000101
As shown in fig. 1 and table 2, it can be seen that the combination of HAP and collagen can significantly reduce the content of melanin; and when one of HAP or collagen is fixed, the addition of the other can significantly reduce melanin, which indicates that the two have obvious synergistic effect on reducing melanin.
Evaluation of Effect
The total effective components are as follows: 8% of the extract is prepared into emulsion, and the effect is examined by human body experiments.
Grouping:
experimental groups: the composition of the functional components is that the proportion of HAP is 4 percent and the proportion of collagen is 4 percent;
control group 1: products using 8% HAP alone;
control group 2: products using 8% collagen alone;
example 2
Nevus-lightening/removing method
1. The evaluation method comprises the following steps:
selecting healthy adults and parts with melanin nevus growth, selecting a 2cm by 2cm tested area, and counting the number of the melanin nevus in the tested area.
The tested product is issued and used twice a day, once in the morning and at night, and the face is cleaned. Other nevus-removing products were stopped during the experiment.
Evaluation was performed after continuous use. The doctor and the patient perform grading evaluation according to the following grading standards by adopting self-contextual comparison.
0: melanin nevus is left and protrudes out of the surface of the skin, and the color is not changed;
1: the melanin nevus is reduced and protrudes out of the skin surface (or the melanin nevus is not reduced and the protrusion is reduced), and the color is not changed;
2: the color of the nevus of melanin is lightened or changed from black to yellow brown;
3: the melanin nevus is reduced, the bulge is reduced, and the color is lightened or changed from black to yellow brown;
4: the melanin nevus is reduced, the skin is smooth, and the color is lightened;
5: the nevus is completely removed, no protrusion exists, the skin is smooth, no pigment is left, the skin color is consistent with the surrounding skin color, and the position of the original melanin nevus is difficult to distinguish.
Wherein: 1. level 2 is valid; 3. grade 4 is significant effect; grade 5 is curative.
TABLE 390 days of Experimental results
Figure BDA0002466052920000111
The results are shown in fig. 2 and table 3, and it can be seen that when HAP and collagen exist together, the effective rate of the traditional Chinese medicine composition for treating nevus is obviously better than that of HAP and collagen alone, and even the effect of removing (curing) nevus can be achieved.
Example 3
Speckle reducing, speckle removing, and pigmentation reducing effects
1. The evaluation method comprises the following steps:
selecting healthy adults with spots or pigmentation, taking a 2 cm-by-2 cm area as a tested part, distributing a tested product, using twice a day, once in the morning and at night, and cleaning the face. Other spot-lightening, pigmentation-reducing products were discontinued during the experiment. The evaluation was made based on the degree of skin color reduction.
Evaluation was performed after continuous use. The doctor and the patient perform grading evaluation according to the following grading standards by adopting self-contextual comparison.
0: the areas of the color spots and the pigmentation are not changed, and the color is not changed;
1: the areas of color spots and pigmentation are reduced, and the color is not changed;
2: the areas of the color spots and the pigmentation are not obviously changed, and the color is lightened or changed from black to yellow brown;
3: the color spot and pigmentation area are reduced, and the color is lightened or changed from black to yellow brown;
4: the areas of the color spots and the pigmentation are obviously reduced, and the color is obviously lightened and is close to the color of the surrounding skin;
5: the color spot and pigmentation disappear, and the color is consistent with the surrounding skin color, so that the position of the original color spot and pigmentation is difficult to distinguish.
Wherein: 1. level 2 is valid; 3. grade 4 is significant effect; grade 5 is curative.
TABLE 490 day test results
Figure BDA0002466052920000121
As shown in fig. 3 and table 4, it can be seen that the effect of lightening spots and reducing pigmentation is significantly better than the case of using HAP alone and collagen alone when HAP and collagen are present simultaneously, and the effect of lightening spots is significant; the effect of HAP alone is also significantly better than collagen alone.
Example 4
Whitening
1. The evaluation method comprises the following steps:
selecting healthy adults, and selecting a region of 2cm x 2cm on the inner side of the forearm of the healthy adults as a teaching part.
The test products were dispensed twice daily and after cleaning, 0.3g of the test product was evenly spread over the test area, once in the morning and once in the evening. Other skin lightening and whitening products were discontinued during the experiment.
After continuous use, the difference in chromaticity at the site to be tested was measured using a Lab colorimetric system spectrophotometer and evaluated.
2. The instrument comprises the following steps: chromameter CR-400 color meter, manufactured by Konica Minolta Sensing, Inc. of Japan.
3. Testing indexes are as follows:
l is the brightness, and the larger the value is, the more towards white; a is red and green; b is yellow and blue. In a Lab colorimetric system, the coordinate differences Δ L, Δ a and Δ b represent color differences;
integral index of chromatic aberration Δ Eab＝[(ΔL)2+(Δa)2+(Δb)2]1/2。
By comparison of Δ EabThe whitening effect of the product is judged according to the index.
4. Statistical analysis and significance analysis were performed on skin color parameters using Statistica statistical software. And (4) performing paired t-test, and analyzing whether the difference between the initial value and the final value of the parameter before and after the application of the product is significant, wherein the significance is significant when P is less than 0.05.
5. The experimental results are as follows:
TABLE 7 color difference Δ EabComparison (x + -s)
30d 60d 90d
Experimental group (4% HAP + 4% collagen) 4.69±1.71 5.21±2.32 6.84±2.01*
Control group 1 (8% HAP) 3.49±2.06 4.22±1.26 4.86±1.55
Control 2 (8% collagen) 2.98±1.23 3.10±1.00 3.56±1.23
Group P < 0.05 compared to before use
As shown in table 7, the results of the composite product of HAP and collagen in the experimental group are significant, and when the composite product is used for 90 days, the color difference change is significant (t is 2.721, P is less than 0.05), and the HAP alone has better whitening effect than the collagen alone.
Discussion of the related Art
In conclusion, under the same concentration, in the fields of nevus lightening, speckle lightening, melanin pigmentation reducing and skin whitening, the HAP has an obvious effect when being used alone, the combination of the HAP and the collagen has an obvious synergistic effect, the effect of thoroughly removing the nevus and the speckles can be achieved, the cure rate is improved by 5-6 times compared with that of the HAP used alone, and the effect is excellent.
All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.

Claims (10)

1. Use of an active principle for the preparation of a composition or a formulation or a product intended to: (a) removing moles and/or bland moles; (b) spot removal and/or lightening; and/or (c) reducing pigmentation and/or whitening;
wherein, the active ingredients comprise: (Y1) first active ingredient: hydroxyapatite.
2. The use according to claim 1, wherein the active ingredients comprise: (Y1) first active ingredient: hydroxyapatite; and (Y2) a second active ingredient: collagen protein.
3. Use according to claim 2, wherein the mass ratio of the first active ingredient to the second active ingredient is 1:10 to 10:1, preferably 1: 5-5:1, preferably 1:2-2: 1.
4. The use according to claim 1, wherein said composition comprises:
(Y1) first active ingredient: hydroxyapatite;
(Y2) second active ingredient: collagen protein; and
(Z) a pharmaceutically or cosmetically acceptable carrier.
5. The use of claim 1, wherein the composition is in a dosage form selected from the group consisting of: solid, semi-solid, or liquid dosage forms, such as solutions, gels, creams, lotions, ointments, creams, pastes, cakes, powders, patches, and the like.
6. A composition, characterized in that the composition comprises:
(Y1) first active ingredient: hydroxyapatite;
(Y2) second active ingredient: collagen protein; and
(Z) a pharmaceutically or cosmetically acceptable carrier.
7. The composition of claim 6, wherein the hydroxyapatite is selected from the group consisting of: ceramic hydroxyapatite, non-ceramic hydroxyapatite, amorphous hydroxyapatite, calcium deficient hydroxyapatite, amorphous hydroxyapatite, a mixture of hydroxyapatite and calcium phosphate, or a combination thereof; preferably, the calcium deficient hydroxyapatite.
8. The composition according to claim 6, wherein the mass ratio of the first active ingredient to the second active ingredient is 1:10 to 10:1, preferably 1: 5-5:1, preferably 1:2-2: 1.
9. The composition of claim 6, wherein the collagen is selected from the group consisting of: human collagen, bovine collagen, porcine collagen, fish collagen, donkey collagen, or combinations thereof; preferably, fish collagen.
10. The composition of claim 6, wherein the sum of the first active ingredient and the second active ingredient in the composition is 0.1 to 95 wt%, preferably 0.5 to 80 wt%, 1 to 60 wt%, 2 to 50 wt%, 4 to 30 wt%, or 5 to 25 wt%.
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