CN113116763B - Collagenase inhibitor, repairing cream containing collagenase inhibitor and preparation method of repairing cream - Google Patents

Abstract

The invention provides a collagenase inhibitor, repair cream containing the collagenase inhibitor and a preparation method thereof. The collagenase inhibitor comprises: the ginseng extract and the kuh-seng root extract are added in an amount of 51-97% and the kuh-seng root extract is added in an amount of 3-49% based on the total mass of the collagenase inhibitor. The collagenase inhibitor of the present invention has excellent inhibitory effect on collagenase activity and no side effect on human body.

Description

Collagenase inhibitor, repairing cream containing collagenase inhibitor and preparation method of repairing cream

Technical Field

The invention relates to a collagenase inhibitor, a repair cream containing the collagenase inhibitor and a preparation method thereof, belonging to the field of cosmetics.

Background

Collagen is mainly produced by fibroblasts of the dermis layer, is a main component of the dermis layer, can maintain the structure of the skin, and imparts toughness and elasticity to the skin. The collagen content and distribution determine whether the skin is youthful. However, abnormal decrease of collagen content causes thinning of dermis, slackening of skin, loss of elasticity, occurrence of wrinkles, and influence of life quality of people. With the continued intensive research on collagen, researchers have found that collagenase plays an important role in the dynamic balance of skin collagen, and that its overexpression and abnormal activation are one of the main causes of skin aging. Therefore, inhibiting collagenase activity can block skin collagen degradation, increase collagen content, and realize anti-aging effect.

For factors affecting skin collagen content, the main approaches to skin anti-aging and skin care include the following: (1) Increasing collagen synthesis by stimulating proliferation of dermal fibroblasts; (2) The collagen synthesis speed of the fibroblast is stimulated by the active factors, so that the total amount of the collagen in the dermis layer is increased; (3) The catalytic activity of a key enzyme-collagenase for inhibiting collagen degradation in the dermis is used for slowing down the degradation speed of the collagen, so as to achieve the purpose of resisting aging; (4) The sun protection is adopted to prevent ultraviolet rays in sunlight from damaging collagen in skin and slow down photoaging of the skin; (5) The antioxidant is used for removing excessive oxygen free radicals in the skin, so that the induced expression of collagenase and abnormal cross-linking of biomacromolecules are slowed down.

In the prior art, in order to prevent skin from sagging, losing elasticity, wrinkling and the like, and keep skin youthful, anti-aging products mixed with various components such as hydrolyzed collagen, hyaluronic acid, polypeptide, retinol and derivatives thereof have been proposed. However, if these ingredients are used in large amounts, there are problems in terms of anti-aging effects, skin feel in use, and safety. If the molecular weight of the hydrolyzed collagen is too large, the hydrolyzed collagen is not easy to penetrate through the skin barrier of the human body to reach the dermis layer; hyaluronic acid cannot substantially slow down the loss of collagen; polypeptides and retinol present a certain irritation and safety risk to the skin, etc.

Along with the increase of the attention of people to skin health, the development of the natural anti-aging agent with safety, stability, obvious effect and high cost performance becomes one of the main research directions of the current medicine and cosmetic industry, and has very good development prospect.

Disclosure of Invention

Problems to be solved by the invention

In view of the prior art, the hydrolyzed collagen has excessive molecular weight, and is not easy to penetrate through the skin barrier of the human body to reach the dermis; hyaluronic acid cannot substantially slow down the loss of collagen; the invention firstly provides a collagenase inhibitor and a preparation method thereof, wherein the polypeptide and the retinol have certain irritation to skin, safety risk and the like.

Further, the invention also provides a repair cream containing the collagenase inhibitor, and the repair cream has excellent anti-aging effect.

Furthermore, the invention also provides a preparation method of the repair cream, which is simple to operate and easy to obtain raw materials.

Solution for solving the problem

The present invention provides a collagenase inhibitor comprising: the ginseng extract and the kuh-seng root extract are added in an amount of 51-97% and the kuh-seng root extract is added in an amount of 3-49% based on the total mass of the collagenase inhibitor.

The collagenase inhibitor according to the present invention, wherein the mass ratio of the ginseng extract to the kuh-seng extract is 1.1 to 32:1, preferably 2 to 30:1, more preferably 3 to 28:1, still more preferably 4 to 25:1, still more preferably 5 to 22:1, still more preferably 6 to 20:1.

The collagenase inhibitor according to the present invention, wherein the collagenase is a interstitial collagenase.

The invention also provides a preparation method of the collagenase inhibitor, which comprises the step of mixing the components of the collagenase inhibitor.

The invention also provides a repair cream comprising the collagenase inhibitor according to the invention and a penetration enhancer, the collagenase inhibitor being added in an amount of 0.01-10% based on the total mass of the repair cream; the addition amount of the penetration enhancer is 0.01-10%.

The repairing cream according to the present invention, wherein the penetration enhancer comprises one or a combination of two or more of propylene glycol, bis-diethoxydiglycol cyclohexane 1, 4-dicarboxylate and chitosan.

The repairing cream provided by the invention further comprises one or more than two of a humectant, a thickener, a pH regulator, grease, a preservative, a skin conditioner, a skin whitening agent, an emulsifier, a sensitivity-relieving agent, an antioxidant and a fragrance;

Preferably, the humectant is added in an amount of 0.01 to 20% based on the total mass of the repair cream; the addition amount of the thickener is 0.02-1.8%; the addition amount of the pH regulator is 0.01-1%; the addition amount of the grease is 10-30%; the addition amount of the preservative is 0.01-1.5%; the addition amount of the skin whitening agent is 0.01-5%; the addition amount of the emulsifier is 0.01-5%; the addition amount of the skin conditioning agent is 0.01-5%; the addition amount of the sensitivity-relieving agent is 0.01-5%; the addition amount of the antioxidant is 0.01-2%; the addition amount of the aromatic is 0.01-1%.

The repairing cream according to the present invention, wherein the skin conditioner comprises one or a combination of two or more of a kelp extract, a fucus extract, a hydrolyzed collagen, a green algae extract, allantoin, a lactobacillus/soybean fermentation product extract, a ginkgo mistletoe leaf extract, a cogongrass rhizome extract, β -glucan, palmitoyl tripeptide-5, acetyl hexapeptide-8, a cactus extract, and a boletus spirulina extract.

The repairing cream according to the present invention, wherein the skin whitening agent comprises one or a combination of two or more of nicotinamide, dipotassium glycyrrhizinate, magnolia sieboldii extract, kojic acid and its derivatives, arbutin and its derivatives, and vitamin C; and/or the number of the groups of groups,

The sensitivity-relieving agent comprises one or more of Hamamelis mollis flower water, bisabolol, stearyl glycyrrhetinate, herba Centellae extract and rhizoma Zingiberis recens extract.

The invention also provides a preparation method of the repair cream, which comprises the step of mixing the components of the repair cream.

ADVANTAGEOUS EFFECTS OF INVENTION

The collagenase inhibitor of the present invention has excellent inhibitory effect on collagenase activity and no side effect on human body.

The repairing cream disclosed by the invention is mild in formula, and can effectively improve skin elasticity, so that an anti-aging effect is achieved.

The preparation method of the repair cream is simple to operate, raw materials are easy to obtain, and the repair cream can be produced in batches.

Drawings

FIG. 1 is a graph showing the relationship between the logarithmic mass concentration of ginseng extract of comparative examples 1 to 5 of the present invention and the inhibition ratio of collagenase activity;

FIG. 2 is a graph showing the relationship between the logarithmic mass concentration and the collagenase activity inhibition ratio of the kuh-seng root extract of comparative examples 6 to 10 of the present invention;

FIG. 3 is a graph showing the relationship between the logarithmic mass concentration of collagenase inhibitor and the inhibition rate of collagenase activity in examples 1 to 5 of the present invention;

FIG. 4 is a graph showing the relationship between the content of ginseng extract and the interaction coefficient in the collagenase inhibitors of examples 1 to 5 of the present invention.

Fig. 5 shows a comparative graph of skin elasticity change rates of application examples 1 to 5 of the present invention and application comparative examples 1 to 8.

Detailed Description

Various exemplary embodiments, features and aspects of the invention are described in detail below. The word "exemplary" is used herein to mean "serving as an example, embodiment, or illustration. Any embodiment described herein as "exemplary" is not necessarily to be construed as preferred or advantageous over other embodiments.

Furthermore, in the following detailed description, numerous specific details are set forth in order to provide a better illustration of the invention. It will be understood by those skilled in the art that the present invention may be practiced without some of these specific details. In other instances, well known methods, procedures, means, equipment and steps have not been described in detail so as not to obscure the present invention.

It should be noted that:

in the present specification, the use of the meaning of "can" or "can" includes both the meaning of performing a certain process and the meaning of not performing a certain process.

In the present specification, the numerical range indicated by the term "numerical value a to numerical value B" means a range including the end point numerical value A, B.

Unless otherwise indicated, all units used in the present invention are international standard units, and numerical values, ranges of values, appearing in the present invention should be understood to include errors permitted in industrial production.

Reference throughout this specification to "some specific/preferred embodiments," "other specific/preferred embodiments," "an embodiment," and so forth, means that a particular element (e.g., feature, property, and/or characteristic) described in connection with the embodiment is included in at least one embodiment described herein, and may or may not be present in other embodiments. In addition, it is to be understood that the elements may be combined in any suitable manner in the various embodiments.

<First aspect>

In a first aspect, the present invention provides a collagenase inhibitor comprising: the ginseng extract and the kuh-seng root extract are added in an amount of 51-97% and the kuh-seng root extract is added in an amount of 3-49% based on the total mass of the collagenase inhibitor.

The inventors of the present invention found that using a combination of kuh-seng extract and ginseng extract can produce excellent synergistic effects, so that collagenase activity can be suppressed to achieve an anti-aging effect.

Specifically, in the present invention, the mass ratio of the ginseng extract to the kuh-seng extract is 1.1 to 32:1, preferably 2 to 30:1, more preferably 3 to 28:1, still more preferably 4 to 25:1, still more preferably 5 to 22:1, still more preferably 6 to 20:1. When the mass ratio of the ginseng extract to the kuh-seng extract is within the above range, it is possible to further have a synergistic effect and an excellent effect of inhibiting collagenase activity.

The method for producing the collagenase inhibitor of the present invention is not particularly limited, and may be a method commonly used in the art, and may specifically include a step of mixing the components of the collagenase inhibitor. For example, the ginseng extract and the kuh-seng root extract are uniformly mixed by adopting a conventional mixing manner.

Collagenase enzyme

Collagenases belong to the class of matrix metalloproteinases (Matrix Metalloproteinase, MMPs). Matrix metalloproteinases are a family of endopeptidases whose biological activity depends on zinc ions and which have the ability to degrade the extracellular Matrix (ECM). The main function of collagenase is to degrade collagen and elastin in dermis, and its tissue type inhibitor (Tissue Inhibitors of Metalloproteinase, TIMPs) specifically inhibits collagenase activity by covalent binding to its highly conserved zinc binding site, and together regulate matrix metabolism, maintaining the structure of dermis.

Collagenases include interstitial collagenase (MMP-1), polymorphonuclear collagenase (MMP-8) and collagenase 3 (MMP-13). Wherein, the interstitial collagenase is also called collagenase-1, has multiple functions and can act on different substrates. The matrix collagenase is capable of degrading several matrix molecules such as aggrecan, multipolycan, decorin, casein, entactin, serine protein inhibitors and mucin-C. Thus, the interstitial collagenase plays a key role in the physiological repair of the extracellular matrix. The invention is mainly based on the important role of the interstitial collagenase in the skin aging process, and can inhibit the activity of the interstitial collagenase, thereby reducing skin inflammatory reaction and wrinkles, and being used as a way for delaying aging so as to realize the anti-aging effect.

It should be noted that the purpose of the collagenase inhibitor of the present invention is to inhibit collagenase activity, not collagenase expression, for example: inhibiting the activity of interstitial collagenase.

Ginseng extract

Ginseng (Panax ginseng c.a. meyer) is a perennial herb of the family Araliaceae (Araliaceae), and ginseng is one of the most potential medicinal plant resources for developing in Changbai mountain.

Ginseng contains various chemical components, for example: ginsenoside, ginseng polysaccharide, ginseng protein, polypeptide, etc. Wherein, ginsenoside (ginsenosides) is a steroid compound, and is a triterpene saponin with dammarane type structure and four-ring triterpene as main structure. Ginsenoside is one of the representative active ingredients in ginseng, and is widely present in plants of genus ginseng. The ginseng polysaccharide is another effective active ingredient of ginseng, and is a good natural medicinal ingredient. The ginseng polysaccharide and the micromolecular chemotherapeutic drug are combined for application, so that the damage of the chemotherapeutic drug to the immune system of a human body can be repaired and reduced, and the synergistic and toxicity-reducing effects are exerted.

The ginseng extract can be used as a natural additive for cosmetic production. Ginsenoside has antioxidant, ultraviolet-proof and skin protecting effects, and is one of physiological active substances in Ginseng radix. The ginsenoside can also stimulate the activity of skin fibroblast, promote collagen synthesis, and increase SOD content and activity in skin. When the ginsenoside content in the ginseng extract is high, DPPH (1, 1-diphenyl-2-trinitrophenylhydrazine) free radical can be eliminated.

In the present invention, the ginseng extract is added in an amount of 51 to 97% by weight based on the total mass of the collagenase inhibitor. When the addition amount of the ginseng extract is 51-97%, the collagenase activity can be effectively inhibited. Specifically, the ginseng extract may be added in an amount of 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, etc.

Kuh-seng root extract

The radix Sophorae Flavescentis is dried root of Sophora flavescens (Sophora flavescens Alt.) of Sophora (Sophora) of Leguminosae (Leguminosae). Radix Sophorae Flavescentis is herb or sub-shrub, is in shrub shape, and is produced in regions of south and north provinces in China, india, japan, korea, russian Siberian, etc. The radix Sophorae Flavescentis can be planted in hillside or sand grass slope shrubs or near field, and has an altitude below 1500 m.

The kuh-seng has the effects of clearing heat, drying dampness and promoting urination. Has been used as bitter stomach-invigorating agent, diuretic and antiinflammatory. The chemical components of the composition mainly comprise alkaloid and flavonoid compounds, and dialkyl chromone, quinone and triterpene saponin. Wherein the alkaloid component mainly contains matrine, sophocarpine, oxymatrine, sophoridine, etc.

The prenylflavonoids in radix Sophorae Flavescentis can reduce melanin production, and has skin whitening effect. Matrine can reduce anaphylaxis medium release, can be used as immunosuppressant, and radix Sophorae Flavescentis extract can promote growth and repair of injured vascular nerve cells, recover subcutaneous capillary cell activity, and make skin compact and smooth.

In the present invention, the amount of the extract of kuh-seng root added is 3-49% based on the total mass of the collagenase inhibitor. When the adding amount of the kuh-seng root extract is 3-49%, the collagenase activity can be effectively inhibited. Specifically, the amount of the kuh-seng root extract added may be 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, etc.

<Second aspect>

In a second aspect the present invention provides a repair cream comprising a collagenase inhibitor according to the first aspect of the invention and a penetration enhancer; by adding a proper amount of collagenase inhibitor, the invention can inhibit the activity of collagenase, especially the activity of interstitial collagenase, so that the repairing cream has excellent anti-aging effect and can improve skin elasticity. In order to promote the absorption of collagenase inhibitors by the skin, the cream of the present invention also uses a penetration enhancer. The collagenase inhibitors of the present invention can be used to a greater extent by using a permeation enhancer.

Wherein the collagenase inhibitor is added in an amount of 0.01 to 10% by weight based on the total mass of the repair cream, for example: 0.5%, 1%, 2%, 3%, 5%, 6%, 7%, 8%, etc. When the collagenase inhibitor is added in an amount of between 0.01 and 10%, the skin elasticity after the use of the collagenase inhibitor increases. When the addition amount of the collagenase inhibitor is less than 0.01%, the anti-aging effect cannot be achieved; when the addition amount of the collagenase inhibitor is more than 10%, the content of the collagenase inhibitor is too high, the cost is too high, and the corresponding anti-aging effect is not obviously improved.

The penetration enhancer is added in an amount of 0.01-10% based on the total mass of the repair cream. When the addition amount of the permeation enhancer is less than 0.01%, the permeation enhancer effect is not obvious. When the addition amount of the permeation enhancer is more than 10%, the permeation enhancer cannot further act.

In the present invention, the permeation enhancer includes one or a combination of two or more of propylene glycol, bis-diethoxydiglycol cyclohexane 1, 4-dicarboxylate and chitosan. The present invention preferably uses a combination of propylene glycol and bis-diethoxydiglycol cyclohexane 1, 4-dicarboxylate, and the propylene glycol and the bis-diethoxydiglycol cyclohexane 1, 4-dicarboxylate have a synergistic effect, which can make the absorption effect of the collagenase inhibitor more excellent.

When a combination of propylene glycol and bis-diethoxydiglycol cyclohexane 1, 4-dicarboxylate is used as a penetration enhancer, the amount of propylene glycol added is 0.01 to 5% and the amount of bis-diethoxydiglycol cyclohexane 1, 4-dicarboxylate added is 0.01 to 5% based on the total mass of the cream. When the propylene glycol is added in an amount of 0.01 to 5% and the bis-diethoxydiglycol cyclohexane 1, 4-dicarboxylate is added in an amount of 0.01 to 5%, the absorption effect of the collagenase inhibitor can be effectively improved. For example: the amount of propylene glycol added was 0.1%, 0.5%, 1%, 1.5%, 2.5%, 3.5%, 4.5%, etc., and the amount of bis-diethoxydiglycol cyclohexane 1, 4-dicarboxylate added was 0.1%, 0.5%, 1%, 1.5%, 2.5%, 3.5%, 4.5%.

The repairing cream also comprises one or more than two of moisturizer, thickener, pH regulator, grease, preservative, skin conditioner, skin whitening agent, emulsifier, skin soothing agent, antioxidant and aromatic. The repairing cream has mild formula composition, and can fully play the efficacy of the collagenase inhibitor. Specifically:

wherein, the addition amount of the humectant is 0.01-20% based on the total mass of the repair cream, and the moisturizing cream can play a role in moisturizing and supplementing water. In order to further exert the efficacy of the humectant, the humectant of the present invention may be added in an amount of 1 to 19%, 3 to 17%, 4 to 16%, 5 to 15%, 6 to 14%, 7 to 13% and 8 to 12%. When the content of the humectant is less than 0.01%, the moisturizing effect is not obvious; when the content of the humectant is higher than 20%, the repairing cream has sticky feel.

In the invention, the humectant comprises one or more than two of dipropylene glycol, butanediol, glycerol, panthenol, PEG/PPG-17/6 copolymer, betaine, glycereth-26, glycerol polyacrylate, sodium hyaluronate and trehalose. The repairing cream provided by the invention has more excellent moisturizing and moisturizing effects by using the combination of a plurality of humectants.

The amount of the fat added is 10 to 30% by weight of the total mass of the cream, for example, the amount of the fat added may be 12%, 15%, 18%, 20%, 12%, 25%, 28%, or the like. By adding grease into the repair cream, evaporation of moisture on the skin surface can be reduced, and skin chapping can be prevented. In addition, by adding the grease, a hydrophobic film can be formed on the skin surface, and invasion of external harmful substances can be prevented. When the content of the grease is less than 10%, evaporation of moisture on the skin surface cannot be reduced, and invasion of harmful substances cannot be effectively prevented; when the content of the grease is more than 30%, the repairing cream is too greasy, and the use feeling is reduced.

The oil comprises one or more than two of oleyl erucate, cyclomethicone, dimethicone, caprylic/capric triglyceride, hydrogenated polyisobutene, butter tree fruit, ethylhexyl palmitate, hydrogenated polydecene, C20-24 alkyl dimethicone, squalane, C13-14 isoparaffin, cyclohexasiloxane, C12-15 alcohol benzoate, hydrogenated soybean oil and phytosterol.

In the present application, the emulsifier is added in an amount of 0.01 to 5% by weight based on the total mass of the cream, for example: may be 0.1-4.5%, 1-4%, etc. When the dosage of the emulsifier is less than 0.01%, insufficient emulsification is caused, so that the system is unstable; when the amount of the emulsifier is more than 5%, the stability of the product is also affected to some extent.

The emulsifier comprises one or more than two of PEG-10 campesterol, isosteareth-20, sorbitan isostearate, laureth-7, polyglycerol-3 methyl glucose distearate, PEG/PPG-10/1 polydimethylsiloxane, polyglycerol-3 diisostearate, glycerol stearate and PEG-100 stearate.

The present invention can use a complex emulsifier such as a complex of glycerol stearate and PEG-100 stearate, and thus can further provide excellent stability of the cream.

The emulsifying system of the present invention is a non-water-in-oil system, and therefore, when propylene glycol and bis-diethoxydiglycol cyclohexane 1, 4-dicarboxylate are used as the permeation enhancer, the synergistic effect is not affected even if they are not added at the same time.

The thickener is added in an amount of 0.02 to 1.8% by weight based on the total mass of the cream, for example, the thickener may be added in an amount of 0.1%, 0.2%, 0.4%, 0.5%, 0.6%, 0.8%, 1.0%, 1.2%, 1.5%, etc. When the addition amount of the thickener is between 0.02 and 1.8 percent, the thickener has low sticky feel, excellent use feel, good dispersibility and quick absorption. When the addition amount of the thickener is less than 0.02%, the texture of the repairing cream is thinner, and no sticky feeling exists; when the addition amount of the thickener is more than 1.8%, the cream is too thick, and the burden on the skin is increased.

In the present invention, the thickener comprises one or a combination of more than two of xanthan gum, polydimethylsiloxane/vinyl polydimethylsiloxane cross-linked polymer, behenyl alcohol, polyacrylamide, carbomer, hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer, and a complex of isohexadecane, polysorbate-60 and sorbitan isostearate, and ammonium acryloyldimethyl taurate/VP copolymer.

The invention uses the compound thickening agent such as the hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer and the compound of isohexadecane, polysorbate-60 and sorbitan isostearate, and the like, and can improve the stability of the repairing cream.

The addition amount of the pH regulator is 0.01-1% based on the total mass of the repair cream. The pH value of the repair cream is more suitable for human skin by adding the pH regulator. Preferably, the pH adjustor of the present invention may be added in an amount of 0.03 to 0.8%, may be 0.06 to 0.5%, may be 0.1 to 0.3%, etc. When the added amount of the pH adjustor is more than 1% or less than 0.01%, a repair cream having a proper pH cannot be obtained. In the invention, the pH regulator comprises one or more than two of aminomethylpropanol, arginine, citric acid and sodium citrate.

The skin conditioning agent is added in an amount of 0.01-5% based on the total mass of the cream. The skin conditioner may be added in an amount of 0.1-4%, 0.15-3%, 0.2-2%, etc. When the addition amount of the skin conditioning agent is less than 0.01%, the corresponding effect cannot be achieved; when the addition amount of the skin conditioner is more than 5%, the cost is excessively high.

The skin conditioner comprises one or more of a giant alga extract, a fucus extract, a hydrolyzed collagen, a chlorella extract, allantoin, a lactobacillus/soybean fermentation product extract, a ginkgo mistletoe leaf extract, a cogongrass rhizome extract, beta-glucan, palmitoyl tripeptide-5, an acetyl hexapeptide-8, a cactus extract and a bola spirulina extract.

Allantoin can reduce the adhesion of keratinocytes, accelerate the renewal of epidermal cells, enhance the repair ability of skin, and has high safety.

The pure natural extract product of the Bonatate spirulina extract moistens the skin, so that the Bonatate spirulina extract is elastic, moisturizes, tender and tender, provides nutrients for the skin, lightens the phenomenon of darkness and enables the skin to be young and active.

The cream of the present invention may also be added with a small amount of skin whitening agent. The skin whitening agent can play a role in brightening skin color and achieve a certain whitening effect. The addition amount of the skin whitening agent is 0.01-5% based on the total mass of the repair cream; for example, 0.5%, 1%, 2%, 3%, 4% and the like are possible. When the addition amount of the skin whitening agent is less than 0.01%, the content is too low to achieve the corresponding effect; when the addition amount of the skin whitening agent is more than 5%, the cost is excessively high.

The skin whitening agent comprises one or more of nicotinamide, dipotassium glycyrrhizinate, magnolia sieboldii extract, kojic acid and its derivatives, arbutin and its derivatives, and vitamin C.

The addition amount of the sensitivity-relieving agent is 0.01-5% based on the total mass of the repair cream. For example, 0.5%, 1%, 2%, 3% and the like are possible. When the addition amount of the sensitivity-relieving agent is less than 0.01%, the sensitivity-relieving effect is not obvious; when the addition amount of the sensitivity-relieving agent is more than 5%, the effect of relieving the sensitivity cannot be further achieved, and the cost is too high.

In the invention, the sensitivity-relieving agent comprises one or more than two of Hamamelis virginiana flower water, bisabolol, stearyl glycyrrhetinate, centella asiatica extract and ginger root extract. One or a combination of two or more of them.

Wherein the bisabolol is extracted from chrysanthemum plants, has the effects of resisting inflammation and inhibiting bacteria, has good component stability, has good compatibility with skin, reduces skin inflammation, reduces skin acne, prevents acne, improves skin anti-irritation capability, and repairs skin with inflammation injury. Bisabolol has obvious anti-inflammatory, irritation relieving and antiallergic effects.

The antioxidant is added in an amount of 0.01-2% based on the total mass of the repair cream. The invention can prevent oily components such as grease, wax, hydrocarbon and the like of cosmetics from contacting oxygen in the air to generate oxidation, generate peroxides, aldehydes, acids and the like, and lead the cosmetics to be discolored, rancidity, degraded in quality and the like by using the antioxidant. The antioxidant comprises one or more than two of butylhydroxytoluene, lycopene, tocopherol and tocopheryl acetate.

Chelating agents may also be added to the cream of the present invention as appropriate. The chelating agent is added in an amount of 0-1% based on the total mass of the repair cream. The chelating agent may be EDTA-2Na and/or EDTA-4Na, etc.

In addition, the repairing cream also contains preservative and aromatic. The preservative in the repair cream of the invention is added in an amount of 0.01-1.5% by weight of the total mass of the repair cream, and the aromatic is added in an amount of 0.01-1%. The preservative may include one or a combination of two or more of phenoxyethanol, methylparaben, propylparaben, benzoic acid, and salts thereof. The aromatic may be essence, etc.

The repairing cream provided by the invention not only has an anti-aging effect, but also has the functions of moisturizing and water locking, can prevent water loss, and creates a moisturizing barrier for skin. Meanwhile, the repairing cream provided by the invention has a repairing effect on skin and activates the functions of the skin. In addition, the repair cream provided by the invention has strong moistening property and quick absorption.

<Third aspect of the invention>

A third embodiment of the present invention provides a method for preparing the repair cream of the second embodiment, comprising the step of mixing the components of the repair cream.

Specifically, the preparation method of the repair cream comprises the following steps:

1. adding oil, emulsifier, part of thickener, sensitivity-relieving agent, antioxidant, part of antiseptic and aromatic into oil phase pot, stirring and heating to 80-85deg.C to dissolve thoroughly;

2. adding water, humectant, part of penetration enhancer, part of skin conditioner, rest of thickener, pH regulator, and optionally chelating agent into emulsifying pot, stirring and heating to 80-85deg.C to dissolve thoroughly;

3. slowly pumping the oil phase substances in the oil phase pot to an emulsifying pot, stirring, homogenizing, emulsifying in vacuum, and keeping the temperature of the emulsifying pot at 80-85 ℃;

4. cooling to 40-50deg.C, adding skin whitening agent, collagenase inhibitor, residual penetration enhancer, residual skin conditioner and residual antiseptic, and stirring;

5. cooling to 35-40deg.C, discharging, and standing for 12-48 hr.

Examples

Embodiments of the present invention will be described in detail below with reference to examples, but it will be understood by those skilled in the art that the following examples are only for illustrating the present invention and should not be construed as limiting the scope of the present invention. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.

Ginseng extracts were purchased from: to the state market exhibition macro biotechnology limited company;

kuh-seng root extract is purchased from: beijing Bei Lilai S Biochemical Co.

Comparative examples 1 to 5

A ginseng extract is provided as collagenase inhibitor. The ginseng extract is dissolved in 5 groups of deionized water with different volumes to obtain 5 groups of test solutions, wherein the concentration of the 5 groups of test solutions is 4000 mug/mL, 3200 mug/mL, 2400 mug/mL, 1600 mug/mL and 800 mug/mL respectively. The logarithmic mass concentration of the ginseng extract is shown in table 2 and fig. 1 below.

Comparative examples 6 to 10

Radix Sophorae Flavescentis extract is provided as collagenase inhibitor. The kuh-seng extract was dissolved in 5 deionized water groups corresponding to the volumes of comparative examples 1 to 5 to obtain 5 test solutions, and the concentrations of the 5 test solutions were 400. Mu.g/mL, 320. Mu.g/mL, 240. Mu.g/mL, 160. Mu.g/mL, 80. Mu.g/mL, respectively. The logarithmic mass concentration of the kuh-seng extract is shown in table 2 and fig. 1 below.

Examples 1 to 5

Ginseng radix extract and radix Sophorae Flavescentis extract are provided as collagenase inhibitor. Mixing Ginseng radix extract and radix Sophorae Flavescentis extract at mass ratio of 1:2 (example 1), 1:1 (example 2), 5:1 (example 3), 15:1 (example 4), and 20:1 (example 5) to obtain collagenase inhibitor.

The collagenase inhibitors of example 1 were dissolved in 5 sets of deionized water, respectively, to give 5 sets of test solutions, the concentrations of the 5 sets of test solutions being 400 μg/mL, 320 μg/mL, 240 μg/mL, 160 μg/mL, 80 μg/mL, respectively.

The collagenase inhibitors of example 2 were dissolved in 5 deionized water groups, respectively, to give 5 test solutions, the concentrations of the 5 test solutions being 400. Mu.g/mL, 320. Mu.g/mL, 240. Mu.g/mL, 160. Mu.g/mL, 80. Mu.g/mL, respectively.

The collagenase inhibitors of example 3 were dissolved in 5 sets of deionized water, respectively, to give 5 sets of test solutions, the concentrations of the 5 sets of test solutions being 640 μg/mL, 480 μg/mL, 320 μg/mL, 160 μg/mL, 80 μg/mL, respectively.

The collagenase inhibitors of example 4 were dissolved in 5 sets of deionized water, respectively, to give 5 sets of test solutions, the concentrations of the 5 sets of test solutions being 640 μg/mL, 480 μg/mL, 320 μg/mL, 160 μg/mL, 80 μg/mL, respectively.

The collagenase inhibitors of example 5 were dissolved in 5 sets of deionized water, respectively, to give 5 sets of test solutions, the concentrations of the 5 sets of test solutions being 1000. Mu.g/mL, 800. Mu.g/mL, 600. Mu.g/mL, 400. Mu.g/mL, 200. Mu.g/mL, respectively.

Wherein the contents (% by mass) of the ginseng extract and the kuh-seng extract in the collagenase inhibitor are shown in table 1 below, and the logarithmic mass concentrations of the collagenase inhibitor are shown in table 3 below.

TABLE 1

Assay for inhibition of collagenase Activity

The Fu Lin Fen reagent can be reduced to blue by phenol compound (molybdenum blue and tungsten blue mixture) under alkaline condition, and the protein and its hydrolysate can be reacted due to amino acid containing phenol group (such as tyrosine, tryptophan, etc.) in protein molecule, so that the principle can be used for measuring protease activity. Casein is usually used as substrate, and under the condition of a certain pH value and temperature, the casein is hydrolyzed by collagenase, after a period of time, the enzymolysis reaction is stopped by trichloroacetic acid, and then the above-mentioned material is centrifuged or filteredRemoving casein precipitate, collecting supernatant, and treating with Na ₂ CO ₃ Alkalizing, adding Fu Lin Fen reagent to develop color, and measuring the blue color in proportion to the tyrosine amount of the product in the filtrate at 650nm wavelength by a spectrophotometer to calculate the activity of collagenase.

In the test, collagenase was used as matrix collagenase (MMP-1), purchased from: shanghai ze Biotechnology Co., ltd.

Collagenase activity is measured as collagenase activity that catalyzes the production of tyrosine from casein. The method comprises the following steps:

taking 1 test tube, respectively adding 0.25mL of deionized water and 0.25mL of collagenase (32U/mL), then adding 0.5mL (1.0 percent, w/v) of substrate casein solution, immediately mixing, carrying out water bath heat preservation for 10min at 37 ℃, then adding 1mL (6.5 percent, w/v) of trichloroacetic acid solution, mixing uniformly, standing for 10min, centrifuging at 10000rpm for 5min, taking 0.5mL of supernatant sample in the test tube in another test tube, respectively adding 0.5mL (mass concentration: 10 percent) of sodium bicarbonate test solution, and shaking uniformly. After 10 minutes, 0.5ml of Fu Lin Fen test solution (diluted 2 times of Fu Lin Fen test solution with 1mol/L acid concentration) is added respectively, and the mixture is immediately mixed and left at room temperature for 30 minutes; the supernatant 1 of the test group was obtained, and absorbance was measured at a wavelength of 650nm and designated as A1.

Taking 1 test tube, adding deionized water 0.25mL and collagenase 0.25mL (32U/mL) respectively, then adding trichloroacetic acid solution 1mL (6.5%, w/v) and immediately mixing uniformly, carrying out water bath heat preservation for 10min at 37 ℃, then adding substrate casein solution 0.5mL (1.0%, w/v) and mixing uniformly, standing for 10min, centrifuging at 10000rpm for 5min, taking supernatant sample 0.5mL in the test tube into another test tube, adding sodium bicarbonate test solution 0.5mL (mass concentration: 10%) respectively, and shaking uniformly. After 10 minutes, 0.5ml of Fu Lin Fen test solution (diluted 2 times of Fu Lin Fen test solution with 1mol/L acid concentration) is added respectively, and the mixture is immediately mixed and left at room temperature for 30 minutes; control supernatant 2 was obtained, and absorbance was measured at a wavelength of 650nm and designated as A2.

0.25mL (32U/mL) of collagenase is added into 35 test tubes respectively, then 0.25mL of the test solutions of comparative examples 1-10 and examples 1-5 are added respectively and mixed evenly, then 0.5mL (1.0 percent, w/v) of substrate casein solution is added and mixed evenly immediately, after water bath heat preservation is carried out for 10min at 37 ℃, 1mL (6.5 percent, w/v) of trichloroacetic acid solution is added and mixed evenly, after standing for 10min, centrifugation is carried out for 5min at 10000rpm, 0.5mL of supernatant fluid sample in 35 test tubes is taken into 35 other test tubes respectively, and 0.5mL (mass concentration: 10 percent) of sodium bicarbonate test solution is added respectively and mixed evenly. After 10 minutes, 0.5ml of Fu Lin Fen test solution (diluted 2 times of Fu Lin Fen test solution with 1mol/L acid concentration) is added respectively, and the mixture is immediately mixed and left at room temperature for 30 minutes; 35 experimental group supernatants 3 were obtained, each absorbance was measured at a wavelength of 650nm and designated A3.

0.25mL (32U/mL) of collagenase is added into 35 test tubes respectively, then 0.25mL of the test solutions of comparative examples 1-10 and examples 1-5 are added respectively and mixed evenly, then 1mL (6.5%, w/v) of trichloroacetic acid solution is added and mixed evenly immediately, after water bath heat preservation is carried out for 10min at 37 ℃, 0.5mL (1.0%, w/v) of substrate casein solution is added and mixed evenly, after 10min standing, centrifugation is carried out for 5min at 10000rpm, 0.5mL of supernatant fluid samples in 35 test tubes are taken into 35 other test tubes respectively, and 0.5mL (mass concentration: 10%) of sodium bicarbonate test solution is added respectively and shaken evenly. After 10 minutes, 0.5ml of Fu Lin Fen test solution (diluted 2 times of Fu Lin Fen test solution with 1mol/L acid concentration) is added respectively, and the mixture is immediately mixed and left at room temperature for 30 minutes; 35 control supernatants 4 were obtained, each absorbance detected at a wavelength of 650nm, designated A4.

Inhibition ratio = [1- (A3-A4)/(A1-A2) ] ×100%

Wherein: a1 is absorbance of supernatant 1 of the experimental group without collagenase inhibitor;

a2 is absorbance of supernatant 2 of control group without collagenase inhibitor;

a3 is absorbance of supernatant 3 of the experimental group containing collagenase inhibitor;

a4 is absorbance of supernatant 4 of control group containing collagenase inhibitor.

The inhibition ratios of collagenase activities by the ginseng extracts (comparative examples 1 to 5) and the kuh-seng extracts (comparative examples 6 to 10) were calculated, respectively. And combining the logarithmic mass concentration-collagenase activity inhibition ratio relationship graph (FIGS. 1 and 2), and converting to obtain the corresponding mass concentration (IC) when the inhibition ratio of Ginseng radix extract is 50% _50A ) Quality corresponding to 50% inhibition rate of radix Sophorae Flavescentis extractConcentration (IC) _50B ) The results are shown in Table 2.

TABLE 2

The collagenase activity inhibition rate of the collagenase inhibitors of examples 1 to 5 was then measured. And combining the relation graph (figure 3) of logarithmic mass concentration and collagenase activity inhibition ratio, and obtaining equivalent inhibition ratio (50%) by compounding Ginseng radix extract and radix Sophorae Flavescentis extract by conversion, wherein the mass concentration (IC) of Ginseng radix extract _50a ) When the equivalent inhibition rate (50%) is generated by the combination of the ginseng extract and the kuh-seng extract, the mass concentration ((IC) of the kuh-seng extract _50b ) The results are shown in Table 3.

The effect of the complex action of ginseng extract and kuh-seng extract can be evaluated by using the interaction coefficient gamma, and the specific results are shown in Table 3.

γ＝IC _50a /IC _50A +IC _50b /IC _50B

Wherein the IC _50A Representing the corresponding mass concentration when the inhibition rate of the ginseng extract is 50%;

IC _50B representing the corresponding mass concentration when the inhibition rate of the kuh-seng root extract is 50%;

IC _50a representing the mass concentration of the ginseng extract when the equivalent inhibition rate (50%) is generated by the composite action of the ginseng extract and the kuh-seng extract;

IC _50b indicating the mass concentration of the kuh-seng root extract when the equivalent inhibition rate (50%) is generated by the compound action of the ginseng extract and the kuh-seng root extract.

Wherein γ=1, representing that the ginseng extract and the kuh-seng extract exhibit a simple additive effect; gamma < 1 is that the ginseng extract and the kuh-seng root extract show a synergistic effect, and the smaller the gamma value is, the stronger the synergistic effect is; gamma > 1 is the antagonistic effect of the ginseng extract and the kuh-seng extract, and the greater the gamma value, the greater the antagonistic effect.

TABLE 3 Table 3

Note that: in Table 3, examples 1 and 2 are presented in the present invention as reference examples 1 and 2, which can be contrasted with examples 3-5.

As can be seen from table 3, the interaction coefficient in the collagenase inhibitor of the present invention is less than 1, and the interaction coefficient thereof may be 0.8 or less, may be 0.7 or less, may be 0.6 or less, and may even be 0.5 or less, so that the ginseng extract and the kuh-seng extract may exhibit excellent synergistic effects.

Application examples 1 to 5

The contents (mass percent) of the components in the cream formulations of application examples 1 to 5 in the following table 4 were used to prepare cream according to the following production process steps. The production process comprises the following steps:

1. adding the phase A raw material into an oil phase pot, stirring and heating to 83 ℃ to fully dissolve the phase A raw material;

2. adding the phase B into an emulsifying pot, stirring and heating to 83 ℃ to fully dissolve the phase B;

3. Slowly pumping the oil phase substances in the oil phase pot to an emulsifying pot, stirring, homogenizing, emulsifying in vacuum, and keeping the temperature of the emulsifying pot at 83 ℃;

4. cooling to 42 ℃, adding phase C and stirring uniformly;

5. cooling to 37 ℃, discharging, and standing for 24 hours;

6. and after the inspection is qualified, sub-packaging and packaging, inspecting again, and warehousing the finished product.

Note that: a, B, C phases in the process are respectively

Phase A: ethylhexyl palmitate, cyclomethicone, caprylic/capric triglyceride, oleyl erucate, polyglyceryl-3 methyl glucose distearate, shea butter, dimethicone, cyclohexasiloxane, glycerol stearate and PEG-100 stearate complexes, C12-15 alcohol benzoate, ammonium/VP or sodium acrylate/sodium acrylate dimethyl taurate copolymers, squalane, hydroxyethyl acrylate/sodium acrylate copolymers and complexes of isohexadecane and polysorbate-60 and sorbitan isostearate, stearyl glycyrrhetinate, tocopheryl acetate, bisabolol, methylparaben, propylparaben, butylhydroxytoluene, fragrances;

and B phase: water, glycerol, propylene glycol, butylene glycol, panthenol, dipropylene glycol, allantoin, betaine, carbomer, aminomethylpropanol;

And C phase: ginseng extract, kuh-seng extract, phenoxyethanol, bolsteride spirulina extract, dipotassium glycyrrhizinate, lactobacillus/soybean fermentation product extract, and bis-diethoxydiglycol cyclohexane 1, 4-dicarboxylic acid ester.

Wherein ethylhexyl palmitate, cyclomethicone, caprylic/capric triglyceride, oleyl erucic ester, butter fruit fat, dimethicone, cyclohexasiloxane, C12-15 alcohol benzoate, squalane are oils;

the complex of polyglycerol-3 methyl glucose distearate, glycerol stearate and PEG-100 stearate is an emulsifier;

hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer and isohexadecane and polysorbate-60 and sorbitan isostearate, ammonium acryloyldimethyl taurate/VP copolymer, carbomer are thickeners;

glycerin, butylene glycol, panthenol, dipropylene glycol, betaine are humectants;

propylene glycol, bis-diethoxydiglycol cyclohexane 1, 4-dicarboxylate are permeation promoters;

aminomethylpropanol is a pH adjuster;

lactobacillus/soybean fermentation product extract, bolsterium extract, allantoin are skin conditioning agents.

The Ginseng radix extract and radix Sophorae Flavescentis extract are collagenase inhibitor;

Dipotassium glycyrrhizinate is a skin whitening agent; stearyl glycyrrhetinate and bisabolol are allergy-relieving agents;

butylated hydroxytoluene, lycopene, tocopheryl acetate are antioxidants;

the essence is aromatic; phenoxyethanol, methylparaben, and propylparaben are preservatives.

In the invention, the compound of glycerol stearate and PEG-100 stearate is manufactured by Heda, model: arlael 165;

hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer and isohexadecane and polysorbate-60 and sorbitan isostearate, manufacturer: french Sibirch Co.

Comparative examples 1 to 8 were used

According to the contents (mass percentages) of the respective components in the cream formulations of application comparative examples 1 to 8 in the following table 5, cream was prepared in the same manner as in application examples 1 to 5.

TABLE 4 Table 4

TABLE 5

Skin elasticity test

Skin elasticity test method: the test principle is based on suction and stretching, and the suction pressure generated on the surface of the tested skin sucks the skin into a specific test probe, and the depth of the skin sucked into the test probe is measured by a non-contact optical test system. The test probe includes a light emitter and a light receiver, and the ratio of light (the ratio of emitted light to received light) is proportional to the depth of skin drawn into the probe, thus obtaining a plot of the length of skin stretched versus time.

Measuring skin elasticity of a subject by using a probe PVM600 of German CK company and a skin elasticity measuring instrument MPA580, selecting a parameter R2 as a comparison index (R2: the ratio of the skin rebound amount without negative pressure to the maximum stretching amount with negative pressure is closer to 1, the better the skin elasticity is), measuring 3 times in total, and taking an average value; the improvement of skin elasticity in the test area by the product was evaluated by measuring the change in skin elasticity value R2 before and after use of the product.

The number of subjects was 33, the test period was 8 weeks, the application of the repair cream of examples 1 to 5 and the application of the repair cream of comparative examples 1 to 8 were selected as test samples, 13 different areas were divided in the forearm of the subjects, the repair cream of examples 1 to 5 and the repair cream of comparative examples 1 to 8 were applied to the different areas on the inner side of the forearm respectively in the morning and evening every day, and the application amount was about 2mg/cm ² The application position of each test sample in the test period is kept unchanged, and then the skin elasticity of the tested area before the test and 8 weeks of use is measured respectively, so that the change rate of the skin elasticity is further characterized (average value is obtained), and the specific elastic change rate is shown in the table 6 and fig. 5.

TABLE 6

As can be seen from table 6 and fig. 5, the application examples 1 to 5 of the present application have a large rate of change in elasticity, i.e., skin elasticity is enhanced, and thus, skin aging can be effectively improved by using ginseng extract and kuh-seng extract.

The skin elasticity change rate of the present application was small in the application comparative examples 1 to 8, and thus the anti-aging effect of the application comparative examples 1 to 8 was relatively poor.

The above examples of the present application are merely illustrative of the present application and are not intended to limit the embodiments of the present application. Other variations or modifications of the above teachings will be apparent to those of ordinary skill in the art. It is not necessary here nor is it exhaustive of all embodiments. Any modification, equivalent replacement, improvement, etc. which come within the spirit and principles of the application are desired to be protected by the following claims.

Claims (7)

1. A repair cream, characterized by comprising a collagenase inhibitor and a penetration enhancer, wherein the addition amount of the collagenase inhibitor is 0.01-10% based on the total mass of the repair cream; the addition amount of the penetration enhancer is 0.01-10%;

the collagenase inhibitor comprises: the ginseng extract and the kuh-seng root extract are added in an amount of 51-97% by weight of the total mass of the collagenase inhibitor, and the kuh-seng root extract is added in an amount of 3-49%;

The mass ratio of the ginseng extract to the kuh-seng root extract is 15-20:1;

the penetration enhancer comprises one or more than two of propylene glycol, bis-diethoxydiglycol cyclohexane 1, 4-dicarboxylic acid ester and chitosan;

the cream also comprises a humectant, a thickener, a pH regulator, grease, a preservative, a skin conditioner, a skin whitening agent, an emulsifier, a skin soothing agent, an antioxidant and a fragrance.

2. A repair cream according to claim 1, wherein the collagenase is interstitial collagenase.

3. A repair cream according to claim 1, wherein the method of preparing the collagenase inhibitor comprises the step of mixing the components of the collagenase inhibitor.

4. The repair cream according to claim 1, wherein the humectant is added in an amount of 0.01 to 20% based on the total mass of the repair cream; the addition amount of the thickener is 0.02-1.8%; the addition amount of the pH regulator is 0.01-1%; the addition amount of the grease is 10-30%; the addition amount of the preservative is 0.01-1.5%; the addition amount of the skin whitening agent is 0.01-5%; the addition amount of the emulsifier is 0.01-5%; the addition amount of the skin conditioning agent is 0.01-5%; the addition amount of the sensitivity-relieving agent is 0.01-5%; the addition amount of the antioxidant is 0.01-2%; the addition amount of the aromatic is 0.01-1%.

5. The cleansing cream of claim 1, wherein the skin conditioning agent comprises one or a combination of two or more of a kelp extract, a fucus extract, hydrolyzed collagen, a green algae extract, allantoin, a lactobacillus/soybean fermentation product extract, a ginkgo mistletoe leaf extract, a cogongrass rhizome extract, beta-glucan, palmitoyl tripeptide-5, acetyl hexapeptide-8, a cactus extract, a boletus extract.

6. The repairing cream according to claim 1, wherein the skin whitening agent comprises one or a combination of two or more of nicotinamide, dipotassium glycyrrhizinate, magnolia sieboldii extract, kojic acid, arbutin, and vitamin C; and/or the number of the groups of groups,

the sensitivity-relieving agent comprises one or more of Hamamelis mollis flower water, bisabolol, stearyl glycyrrhetinate, herba Centellae extract and rhizoma Zingiberis recens extract.

7. A method of preparing a repair cream as claimed in any one of claims 1 to 6, comprising the step of mixing the components of the repair cream.