CN113116763A - Collagenase inhibitor, repair cream containing the same and preparation method thereof - Google Patents

Abstract

The invention provides a collagenase inhibitor, a repair cream containing the collagenase inhibitor and a preparation method of the repair cream. The collagenase inhibitor comprises: the collagenase inhibitor comprises a ginseng extract and a sophora flavescens root extract, wherein the ginseng extract is added in an amount of 51-97% and the sophora flavescens 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 an excellent inhibitory effect on collagenase activity and has no side effects on the human body.

Description

Collagenase inhibitor, repair cream containing the same and preparation method thereof

Technical Field

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

Background

Collagen is mainly produced by fibroblasts in the dermis layer, is a main component of the dermis layer, and can maintain the structure of the skin and endow the skin with toughness and elasticity. The collagen content and distribution determine the youth or not of the skin. However, abnormal reduction of collagen content causes thinning of the dermis, skin sagging, loss of elasticity, appearance of wrinkles, and affects the quality of life of people. With the ongoing and intensive research on collagen, researchers have found that collagenase plays an important role in the dynamic balance of skin collagen, and its overexpression and abnormal activation are one of the major causes of skin aging. Therefore, inhibiting the activity of collagenase can block the degradation of collagen of skin, increase the content of collagen, and realize the anti-aging effect.

The main approaches to skin anti-aging and skin care include the following aspects, with respect to factors affecting the collagen content of the skin: (1) increasing collagen synthesis by stimulating proliferation of fibroblasts in the dermis layer; (2) increasing the total amount of collagen in the dermis by stimulating the speed of synthesizing collagen by fibroblasts through active factors; (3) the degradation speed of the collagen is slowed down by inhibiting the catalytic activity of collagenase, a key enzyme for degrading the collagen in the dermis, so that the anti-aging purpose is achieved; (4) through sun protection, the damage of ultraviolet rays in sunlight to collagen in the skin is prevented, and the photoaging of the skin is slowed down; (5) the induced expression of collagenase and abnormal cross-linking of biomacromolecules is slowed down by scavenging excess oxygen free radicals in the skin using antioxidants.

In order to prevent skin from sagging, losing elasticity, wrinkling, etc., and keep skin young, anti-aging products mixed with various components such as hydrolyzed collagen, hyaluronic acid, polypeptide, retinol and its derivatives have been proposed in the prior art. However, if these ingredients are used in large amounts, problems arise in the actual anti-aging effect, the feeling of use, and safety. If the molecular weight of the hydrolyzed collagen is too large, the hydrolyzed collagen is not easy to permeate the skin barrier of the human body to reach the dermis; hyaluronic acid cannot essentially slow down the loss of collagen; the polypeptide and the retinol have certain irritation and safety risks to the skin, and the like.

With the increase of attention of people to skin health, the development of a natural anti-aging agent with safety, stability, obvious effect and high cost performance has become one of the main research directions of the current pharmaceutical and cosmetic industries, and has a very good development prospect.

Disclosure of Invention

Problems to be solved by the invention

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

Further, the present invention also provides a repair cream comprising the collagenase inhibitor, which has an 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.

Means for solving the problems

The present invention provides a collagenase inhibitor comprising: the collagenase inhibitor comprises a ginseng extract and a sophora flavescens root extract, wherein the ginseng extract is added in an amount of 51-97% and the sophora flavescens 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 sophora flavescens root extract is 1.1 to 32:1, preferably 2 to 30:1, more preferably 3 to 28:1, further preferably 4 to 25:1, further preferably 5 to 22:1, and further preferably 6 to 20: 1.

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

The present invention also provides a method for preparing a collagenase inhibitor according to the present invention, comprising the step of mixing the components of a collagenase inhibitor.

The invention also provides a repair cream which comprises the collagenase inhibitor and a penetration promoter, wherein the addition amount of the collagenase inhibitor is 0.01-10% of the total mass of the repair cream; the addition amount of the penetration enhancer is 0.01-10%.

The repair cream comprises one or more of propylene glycol, bis-diethoxydiol cyclohexane 1, 4-dicarboxylate and chitosan.

The repair cream further comprises one or more of a humectant, a thickener, a pH regulator, grease, a preservative, a skin conditioner, a skin whitening agent, an emulsifier, a soothing agent, an antioxidant and an aromatic;

preferably, the addition amount of the humectant is 0.01-20% of the total mass of the repair cream; the addition amount of the thickening agent 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 conditioner is 0.01-5%; the addition amount of the allergy 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 repair cream comprises one or more of a giant kelp extract, an fucus extract, hydrolyzed collagen, a green algae extract, allantoin, a lactobacillus/soybean fermentation product extract, a mistletoe ginkgo leaf extract, a cogongrass rhizome extract, beta-glucan, palmitoyl tripeptide-5, acetyl hexapeptide-8, a cactus extract and a Botania spirulina extract.

The repair cream comprises one or more of niacinamide, dipotassium glycyrrhizinate, magnolia sieboldii extract, kojic acid and derivatives thereof, arbutin and derivatives thereof and vitamin C; and/or the presence of a gas in the gas,

the soothing agent comprises one or more of Hamamelis virginiana water, bisabolol, stearyl glycyrrhetinate, centella asiatica extract, and rhizoma Zingiberis recens root 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 an excellent inhibitory effect on collagenase activity and has no side effects on the human body.

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

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

Drawings

FIG. 1 is a graph showing the logarithmic mass concentration-collagenase activity inhibition ratios of the ginseng extracts of comparative examples 1 to 5 of the present invention;

FIG. 2 is a graph showing the logarithmic mass concentration-collagenase activity inhibition ratios of the extract from Sophora flavescens Aiton of comparative examples 6 to 10 of the present invention;

FIG. 3 is a graph showing the log mass concentration of collagenase inhibitors versus the collagenase activity inhibition rate for examples 1-5 of the present invention;

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

FIG. 5 is a graph showing the comparison of the skin elasticity change rate of examples 1 to 5 of application and comparative examples 1 to 8 of the present invention.

Detailed Description

Various exemplary embodiments, features and aspects of the invention will be described in detail below. The word "exemplary" is used exclusively 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 understanding of the present 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, methods, means, devices and steps which are well known to those skilled in the art have not been described in detail so as not to obscure the invention.

It should be noted that:

in the present specification, the meaning of "may" or "may" 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 represented by "numerical value a to numerical value B" means a range including the end point numerical value A, B.

All units used in the present invention are international standard units unless otherwise stated, and numerical values and numerical ranges appearing in the present invention should be understood to include errors allowed in industrial production.

In the present specification, reference to "some particular/preferred embodiments," "other particular/preferred embodiments," "embodiments," and the like, 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 described elements may be combined in any suitable manner in the various embodiments.

<First aspect>

A first aspect of the invention provides a collagenase inhibitor comprising: the collagenase inhibitor comprises a ginseng extract and a sophora flavescens root extract, wherein the ginseng extract is added in an amount of 51-97% and the sophora flavescens 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 have found that using a combination of the extract of the root of sophora flavescens and the extract of ginseng can produce an excellent synergistic effect, and thus can inhibit the activity of collagenase to achieve an anti-aging effect.

Specifically, in the invention, the mass ratio of the ginseng extract to the sophora flavescens root extract is 1.1-32: 1, preferably 2-30: 1, more preferably 3-28: 1, further preferably 4-25: 1, further preferably 5-22: 1, and further preferably 6-20: 1. When the mass ratio of the ginseng extract to the extract of the root of sophora flavescens is within the above range, a synergistic effect can be further exhibited, and the collagenase activity inhibition effect is excellent.

The method for preparing the collagenase inhibitor of the present invention is not particularly limited, and may be a method generally used in the art, and specifically may include a step of mixing the components of the collagenase inhibitor. For example, the ginseng extract and the extract of the kushen root are mixed uniformly by a conventional mixing method.

Collagenase

Collagenases belong to one class of Matrix Metalloproteinases (MMPs). Matrix metalloproteinases are a family of endopeptidases with a zinc ion-dependent biological activity and the ability to degrade the extracellular Matrix (ECM). Collagenase mainly acts to degrade collagen and elastin in dermis, and its Tissue Type Inhibitor (TIMPs) specifically inhibits the activity of collagenase by covalently binding with its highly conserved zinc binding site, co-regulates the metabolism of the matrix, and maintains the structure of the dermis.

The collagenase includes interstitial collagenase (MMP-1), polymorphonuclear collagenase (MMP-8) and collagenase 3 (MMP-13). Among them, interstitial collagenase, also known as collagenase-1, has various functions and can act on different substrates. Interstitial collagenase degrades several matrix molecules, such as aggrecan, multipotent glycans, basement membrane proteoglycans, casein, nidogen, serine protein inhibitors, and mucin-C. Thus, interstitial collagenases play a key role in the physiological repair of the extracellular matrix. The invention is mainly based on the important function of interstitial collagenase in the skin aging process, and inhibits the activity of interstitial collagenase, thereby reducing the inflammatory reaction and wrinkles of the skin, and being used as a way for delaying aging to realize the anti-aging function.

It is to be noted that the collagenase inhibitor of the present invention is intended 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 herbaceous plant of Araliaceae, and is one of the most potential medicinal plant resources in Changbai mountain.

Ginseng contains a variety of chemical components, such as: ginsenoside, ginseng polysaccharide, ginseng protein, polypeptide and the like. Wherein Ginsenoside (Ginsenoside) is a steroid compound, and is triterpene saponin with dammarane type and tetracyclic triterpene as main structure in chemical structure. Ginsenoside is one of representative active ingredients in ginseng, and is widely present in plants of the genus panax. The ginseng polysaccharide is another effective active ingredient of ginseng and is a good natural drug effect ingredient. The combined application of the ginseng polysaccharide and the small molecular chemotherapeutic drug can repair and reduce the damage of the chemotherapeutic drug to the human immune system, and play the role of synergy and attenuation.

The Ginseng radix extract can be used as a natural additive for cosmetic production. Ginsenoside has effects of resisting oxidation, preventing ultraviolet, and protecting skin, and is one of physiologically active substances in Ginseng radix. Ginsenoside can also stimulate the activity of skin fibroblasts, promote collagen synthesis, and increase the SOD content and activity in skin within a certain range. The Ginseng radix extract has high ginsenoside content, and can scavenge DPPH (1, 1-diphenyl-2-trinitrophenylhydrazine) free radical.

In the invention, the ginseng extract is added in an amount of 51-97% by mass based on the total mass of the collagenase inhibitor. When the addition amount of Ginseng radix extract is 51-97%, 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.

Sophora flavescens root extract

The root of Sophora flavescens ait is dried root of Sophora flavescens ait (Sophora flavescens Alt.) belonging to Sophora of Leguminosae (Leguminosae). Lightyellow sophora root is a herbaceous or subshrubular shrub, is in the form of shrub, and is produced in regions of north and south China, as well as in regions of india, japan, korea, russia, siberia, and the like. The radix sophorae flavescentis can be grown in hillside, sandy grass slope shrubs or near fields, and the altitude is below 1500 meters.

Radix Sophorae Flavescentis has effects of clearing heat, eliminating dampness, and promoting urination. It is used as bitter stomachic, diuretic and anti-inflammatory agent. The chemical components of the composition mainly comprise alkaloid and flavonoid compounds, and dialkyl chromone, quinones and triterpenoid saponin. Wherein the alkaloid components mainly comprise matrine, sophocarpine, oxymatrine, sophoridine, etc.

The prenylflavonoids in radix Sophorae Flavescentis can reduce melanin generation, and has skin whitening effect. The matrine can reduce the release of allergic medium, and can be used as immunosuppressant, and the radix Sophorae Flavescentis extract can promote the growth and repair of damaged blood vessel nerve cells, recover the activity of subcutaneous capillary blood vessel cells, and make skin compact, smooth and firm.

In the invention, the adding amount of the sophora flavescens root extract is 3-49% of the total mass of the collagenase inhibitor. When the adding amount of the extract of the kuh-seng root is 3-49%, the activity of collagenase can be effectively inhibited. Specifically, the addition amount of the extract of the kushen root can be 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60% and the like.

<Second aspect of the invention>

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

Wherein, the addition amount of the collagenase inhibitor is 0.01-10% based on the total mass of the repair cream, such as: 0.5%, 1%, 2%, 3%, 5%, 6%, 7%, 8%, etc. When the collagenase inhibitor is added in an amount of 0.01-10%, the elasticity of the skin after the collagenase inhibitor is used is increased. When the addition amount of the collagenase inhibitor is less than 0.01%, the collagenase inhibitor cannot play a role in resisting aging; 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 addition amount of the penetration enhancer is 0.01-10% of the total mass of the repair cream. When the addition amount of the penetration enhancer is less than 0.01%, the penetration enhancing effect is not significant. When the addition amount of the penetration enhancer is more than 10%, the penetration enhancer cannot further function.

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

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

The repair cream also comprises one or more of a humectant, a thickener, a pH regulator, grease, a preservative, a skin conditioner, a skin whitening agent, an emulsifier, a soothing agent, an antioxidant and an aromatic. The formula of the repair cream is mild, so that the efficacy of the collagenase inhibitor can be fully exerted. Specifically, the method comprises the following steps:

wherein the addition amount of the humectant is 0.01-20% by the total mass of the repair cream, and the repair cream can play a role in moisturizing. In order to further exert the efficacy of the humectant, the humectant can be added in an amount of 1-19%, 3-17%, 4-16%, 5-15%, 6-14%, 7-13%, or 8-12%. When the content of the humectant is less than 0.01%, the moisturizing effect is not obvious; when the content of the moisturizer is more than 20%, the repair cream has a sticky feeling.

In the invention, the humectant comprises one or a combination of more than two of dipropylene glycol, butanediol, glycerol, panthenol, PEG/PPG-17/6 copolymer, betaine, glyceryl polyether-26, glyceryl polyacrylate, sodium hyaluronate and trehalose. The combination of multiple humectants is used, so that the repairing cream has more excellent moisturizing and hydrating effects.

The addition amount of the grease is 10-30% based on the total mass of the repair cream, for example, the addition amount of the grease can be 12%, 15%, 18%, 20%, 12%, 25%, 28% and the like. By adding oil and fat into the repair cream, the evaporation of water on the surface of the skin can be reduced, and the skin can be prevented from being dried and cracked. In addition, by adding oil or fat, a hydrophobic film can be formed on the skin surface to prevent the invasion of harmful substances from the outside. When the content of the oil is less than 10%, evaporation of moisture on the skin surface cannot be reduced, and intrusion of harmful substances cannot be effectively prevented; when the content of the grease is more than 30%, the repair cream is too greasy, and the use feeling is reduced.

The oil comprises one or more of oleyl erucate, cyclomethicone, dimethicone, caprylic/capric triglyceride, hydrogenated polyisobutene, shea butter, 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 invention, the emulsifier is added in an amount of 0.01 to 5% based on the total mass of the cream, for example: may be 0.1 to 4.5%, may be 1 to 4%, etc. When the dosage of the emulsifier is less than 0.01%, the emulsification is insufficient, so that the system is unstable; when the dosage of the emulsifier is more than 5 percent, certain influence on the stability of the product can be caused.

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

In the present invention, a complex emulsifier such as a complex of glyceryl stearate and PEG-100 stearate can be used, and the stability of the repair cream can be further improved.

Since the emulsion system of the present invention is a non-water-in-oil system, when propylene glycol and bis-diethoxydiethylene glycol cyclohexane 1, 4-dicarboxylate are used as permeation promoters, their 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% 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 low-viscosity feeling and excellent use feeling are achieved, the dispersibility is good, and the absorption is fast. When the addition amount of the thickener is less than 0.02%, the texture of the repair cream is thin without any sticky feeling; when the thickener is added in an amount of more than 1.8%, the cream is too thick and heavy, which may increase the burden on the skin.

In the invention, the thickening agent comprises xanthan gum, polydimethylsiloxane/vinyl polydimethylsiloxane cross-linked polymer, behenyl alcohol, polyacrylamide, carbomer, hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer, a compound of isohexadecane, polysorbate-60 and sorbitan isostearate, and one or more of acryloyldimethyl taurate/VP copolymer.

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

The addition amount of the pH regulator is 0.01-1% of 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 amount of the pH adjuster of the present invention added may be 0.03 to 0.8%, 0.06 to 0.5%, 0.1 to 0.3%, or the like. When the addition amount of the pH adjuster is more than 1% or less than 0.01%, a cream having a suitable pH value cannot be obtained. In the invention, the pH regulator comprises one or more of aminomethyl propanol, arginine, citric acid and sodium citrate.

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

The skin conditioner comprises one or more of Macrocystis extract, sea Oak extract, hydrolyzed collagen, Chlorella extract, allantoin, lactobacillus/semen glycines fermentation product extract, folium Ginkgo Visci extract, lalang grass rhizome extract, beta-dextran, palmitoyl tripeptide-5, acetyl hexapeptide-8, radix et caulis Opuntiae Dillenii extract, and Bonnati Spirulina extract.

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

The Bonnate spirulina extract is a pure natural extract product, can moisten skin, enable the skin to be elastic, moisturize, smooth and tender, provide nutrient components for the skin, fade the phenomenon of darkness and enable the skin to be young and active.

The repair cream of the invention can also be added with a small amount of skin whitening agent. The skin whitening agent is added to play a role in brightening the skin color and achieve a certain whitening effect. The addition amount of the skin whitening agent is 0.01-5% of the total mass of the repair cream; for example, it may be 0.5%, 1%, 2%, 3%, 4%, etc. When the addition amount of the skin whitening agent is less than 0.01%, the content is too low to play a corresponding effect; when the amount of the skin whitening agent added is more than 5%, the cost is too 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 soothing and sensitizing agent is 0.01-5% of the total mass of the repairing cream. For example, it may be 0.5%, 1%, 2%, 3%, etc. When the addition amount of the allergy relieving agent is less than 0.01 percent, the allergy relieving effect is not obvious; when the addition amount of the allergy relieving agent is more than 5%, the further allergy relieving effect cannot be achieved, and the cost is too high.

In the invention, the soothing agent comprises one or more of hamamelis 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 functions of anti-inflammation and bacteriostasis, has good stability and good compatibility with skin, reduces skin inflammation, relieves skin acne, prevents pimple generation, improves the anti-irritation capability of the skin, and repairs the skin with inflammation injury. The bisabolol has obvious anti-inflammatory, irritation relieving and antiallergic effects.

The addition amount of the antioxidant is 0.01-2% of the total mass of the repair cream. The invention can prevent the oily components of oil, wax, hydrocarbon and the like of the cosmetics from contacting with oxygen in the air to generate oxidation, generate peroxide, aldehyde, acid and the like, and lead the cosmetics to discolor, rancidity, quality reduction and the like by using the antioxidant. The antioxidant comprises one or more of butylated hydroxytoluene, lycopene, tocopherol and tocopherol acetate.

The repair cream of the present invention may further contain a chelating agent as appropriate. The addition amount of the chelating agent is 0-1% of the total mass of the repair cream. The chelating agent may be EDTA-2Na and/or EDTA-4Na, etc.

In addition, the repair cream also contains a preservative and an aromatic. The addition amount of the preservative in the repair cream is 0.01-1.5% and the addition amount of the aromatic is 0.01-1% of the total mass of the repair cream. The preservative can comprise one or the combination of more than two of phenoxyethanol, methyl hydroxybenzoate, propyl hydroxybenzoate, benzoic acid and salts thereof. The aromatic may be a perfume, etc.

The repair cream disclosed by the invention not only can play a role in resisting aging, but also has the effects of moisturizing and locking water, can prevent water loss and creates a moisturizing barrier for skin. Meanwhile, the repair cream provided by the invention has a repair effect on skin and activates the function of the skin. In addition, the repair cream has strong moistening property and quick absorption.

<Third aspect of the invention>

A third embodiment of the present invention provides a method of 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, sensitizer, antioxidant, part of antiseptic, and aromatic into oil phase pan, stirring, and heating to 80-85 deg.C for dissolving completely;

2. adding water, humectant, partial penetration enhancer, partial skin conditioner, residual thickener, pH regulator, and optionally chelating agent into emulsifying pot, stirring, and heating to 80-85 deg.C for dissolving completely;

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

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

5. cooling to 35-40 deg.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 those skilled in the art will appreciate that the following examples are only illustrative of the present invention and should not be construed as limiting the scope of the present invention. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products commercially available.

The ginseng extracts were purchased from: quzhou City exhibition-macro biotechnology Co., Ltd;

the extract of the roots of kushen was obtained from: beijing Bellais Biochemical Co., Ltd.

Comparative examples 1 to 5

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

Comparative examples 6 to 10

Extract of Sophora flavescens ait is provided as collagenase inhibitor. Dissolving the extract of Sophora flavescens Aiton root in 5 groups of deionized water with the volume corresponding to that of comparative examples 1-5 to obtain 5 groups of test solutions, wherein the concentrations of the 5 groups of test solutions are 400 mug/mL, 320 mug/mL, 240 mug/mL, 160 mug/mL and 80 mug/mL respectively. The log mass concentration of the extract of kushen root is shown in table 2 and fig. 1 below.

Examples 1 to 5

Ginseng radix extract and Sophora flavescens root extract are provided as collagenase inhibitors. The collagenase inhibitor is obtained by mixing the ginseng extract and the extract of the root of Sophora flavescens Aiton at a mass ratio of 1:2 (example 1), 1:1 (example 2), 5:1 (example 3), 15:1 (example 4) and 20:1 (example 5).

The collagenase inhibitors of example 1 were dissolved in 5 groups of deionized water to give 5 groups of test solutions, the concentrations of the 5 groups of 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 collagenase inhibitors of example 2 were dissolved in 5 groups of deionized water to give 5 groups of test solutions, the concentrations of the 5 groups of 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 collagenase inhibitors of example 3 were dissolved in 5 groups of deionized water to give 5 groups of test solutions, the concentrations of the 5 groups of test solutions were 640. mu.g/mL, 480. mu.g/mL, 320. mu.g/mL, 160. mu.g/mL, 80. mu.g/mL, respectively.

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

The collagenase inhibitors of example 5 were dissolved in 5 groups of deionized water to give 5 groups of test solutions, the concentrations of the 5 groups of test solutions were 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 sophora flavescens ait root extract in the collagenase inhibitor are shown in table 1 below, and the logarithmic mass concentration of the collagenase inhibitor is shown in table 3 below.

TABLE 1

Collagenase activity inhibition assay

The forskolin phenol reagent can be reduced by phenolic compounds to be blue (a mixture of molybdenum blue and tungsten blue) under alkaline conditions, and because the protein molecules contain amino acid containing phenolic groups (such as tyrosine, tryptophan and the like), the protein and the hydrolysate thereof can be subjected to the reaction, so that the protease activity can be measured by utilizing the principle. Generally, casein is used as a substrate, the casein is hydrolyzed by collagenase under certain pH value and temperature conditions, the enzymolysis reaction is stopped by trichloroacetic acid after a period of time, the supernatant is taken after the casein precipitate is removed by centrifugation or filtration, and Na is used₂CO₃Alkalizing, adding Folin phenol reagent, developing, wherein the shade of blue is proportional to the amount of tyrosine in the filtrate, and measuring with spectrophotometer at 650nm wavelength to calculate the activity of collagenase.

In the test, all collagenases used were matrix collagenase (MMP-1), purchased from: shanghai ze leaf Biotech Co., Ltd.

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

taking 1 test tube, respectively adding 0.25mL of deionized water and 0.25mL (32U/mL) of collagenase, then adding 0.5mL (1.0%, w/v) of substrate casein solution, immediately mixing, keeping the temperature in a water bath at 37 ℃ for 10min, then adding 1mL (6.5%, w/v) of trichloroacetic acid solution, mixing, standing for 10min, centrifuging at 10000rpm for 5min, taking 0.5mL of a supernatant sample in the test tube, respectively adding 0.5mL (mass concentration: 10%) of sodium bicarbonate test solution, and shaking uniformly. After 10 minutes, respectively adding 0.5ml of forinophenol test solution (diluted by 2 times by 1mol/L acid concentration of the forinophenol test solution), immediately mixing uniformly, and standing for 30 minutes at room temperature; the supernatant 1 of the experimental group was obtained and the absorbance at a wavelength of 650nm was measured and recorded as A1.

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

Adding 0.25mL (32U/mL) of collagenase into 35 test tubes respectively, then adding 0.25mL (1.0%, w/v) of the test solution of the comparative examples 1-10 and the examples 1-5 respectively and mixing uniformly, then adding 0.5mL (1.0%, w/v) of the casein solution of the substrate and mixing uniformly immediately, after preserving the temperature in a water bath at 37 ℃ for 10min, then adding 1mL (6.5%, w/v) of trichloroacetic acid solution and mixing uniformly, standing for 10min and centrifuging for 5min at 10000rpm, taking 0.5mL of supernatant samples in the 35 test tubes respectively, adding 0.5mL (mass concentration: 10%) of sodium bicarbonate test solution into another 35 test tubes respectively, and shaking uniformly. After 10 minutes, respectively adding 0.5ml of forinophenol test solution (diluted by 2 times by 1mol/L acid concentration of the forinophenol test solution), immediately mixing uniformly, and standing for 30 minutes at room temperature; 35 groups of experimental group supernatants 3 were obtained and absorbance was measured at 650nm and recorded as A3.

Adding 0.25mL (32U/mL) of collagenase into 35 test tubes respectively, then adding 0.25mL of the test solution of the comparative examples 1-10 and the examples 1-5 respectively and uniformly mixing, then adding 1mL (6.5%, w/v) of trichloroacetic acid solution and immediately uniformly mixing, after preserving heat in a water bath at 37 ℃ for 10min, then adding 0.5mL (1.0%, w/v) of a substrate casein solution and uniformly mixing, standing for 10min and then centrifuging at 10000rpm for 5min, taking 0.5mL of supernatant samples in the 35 test tubes respectively, adding 0.5mL (mass concentration: 10%) of sodium bicarbonate test solution into the other 35 test tubes respectively, and uniformly shaking. After 10 minutes, respectively adding 0.5ml of forinophenol test solution (diluted by 2 times by 1mol/L acid concentration of the forinophenol test solution), immediately mixing uniformly, and standing for 30 minutes at room temperature; 35 control group supernatant 4 was obtained and absorbance was measured at 650nm and recorded as A4.

The inhibition rate is [1- (A3-A4)/(A1-A2) ] x 100%

In the formula: a1 is the absorbance of supernatant 1 of experimental group without adding collagenase inhibitor;

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

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

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

The respective inhibition rates of the ginseng extract (comparative examples 1-5) and the kuh-seng root extract (comparative examples 6-10) on the collagenase activity were calculated. Combining the logarithmic mass concentration-collagenase activity inhibition ratio relationship chart (figure 1 and figure 2), and calculating the corresponding mass concentration (IC) when the inhibition ratio of the ginseng extract is 50%_50A) The mass concentration (IC) corresponding to 50% inhibition rate of Sophora flavescens Aiton root extract_50B) The results are shown in Table 2.

TABLE 2

Then, the collagenase activity inhibition rates of the collagenase inhibitors of examples 1 to 5 were measured. And calculating the mass concentration (IC) of Ginseng radix extract when the combined effect of Ginseng radix extract and radix Sophorae Flavescentis extract generates equivalent inhibition rate (50%) by combining the logarithmic mass concentration-collagenase activity inhibition rate (figure 3)_50a) When the compound action of the ginseng extract and the sophora flavescens root extract generates equivalent inhibition rate (50%), the mass concentration of the sophora flavescens root extract ((IC)_50b) The results are shown in Table 3.

The effect of the combined action of the ginseng extract and the extract of kushen root can be evaluated by the interaction coefficient γ, and the specific results are shown in table 3.

γ＝IC_50a/IC_50A+IC_50b/IC_50B

Wherein, IC_50ARepresents the mass concentration corresponding to the inhibition rate of the ginseng extract of 50%;

IC_50Brepresents the mass concentration corresponding to the inhibition rate of 50% of the extract of the sophora flavescens roots;

IC_50athe ginseng extract and the extract of the root of Sophora flavescensMass concentration of the ginseng extract when the extract composite effect generates equivalent inhibition rate (50%);

IC_50bthe mass concentration of the extract of the sophora flavescens ait root is expressed when the compound action of the extract of the ginseng and the extract of the sophora flavescens ait root generates an equivalent inhibition rate (50%).

Wherein γ ═ 1, indicates that the ginseng extract and the sophora flavescens root extract exhibit a simple additive effect; gamma is less than 1, the ginseng extract and the sophora flavescens root extract show synergistic effect, and the smaller the gamma value is, the stronger the synergistic effect is; gamma is more than 1, the ginseng extract and the sophora flavescens root extract show antagonistic effect, and the larger the gamma value is, the larger the antagonistic effect is.

TABLE 3

Note: in Table 3, examples 1 and 2 are embodied in the present invention as reference examples 1 and 2, which can be compared with examples 3 to 5.

As can be seen from table 3, the collagenase inhibitor of the present invention has an interaction coefficient of less than 1, and the value of the interaction coefficient thereof may be 0.8 or less, 0.7 or less, 0.6 or less, and even 0.5 or less, so that the ginseng extract and the sophora flavescens root extract may exhibit excellent synergistic effects.

Application examples 1 to 5

The repairing cream is prepared according to the content (mass percentage) of each component in the repairing cream formula of the application examples 1-5 in the following table 4 and 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 phase B into an emulsifying pot, stirring and heating to 83 ℃, and fully dissolving;

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

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

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

6. and (5) after the inspection is qualified, subpackaging, packaging, inspecting again, and warehousing the finished product.

Note: the A, B, C phases in the process are respectively

Phase A: ethylhexyl palmitate, cyclomethicone, caprylic/capric triglyceride, oleyl erucate, polyglyceryl-3-methylglucdistearate, shea butter, dimethicone, cyclohexasiloxane, a complex of glyceryl stearate and PEG-100 stearate, C12-15 alcohol benzoate, ammonium acryloyldimethyltaurate/VP copolymer or hydroxyethyl acrylate/sodium acryloyldimethyltaurate copolymer, squalane, hydroxyethyl acrylate/sodium acryloyldimethyltaurate copolymer and a complex of isohexadecane and polysorbate-60 and sorbitan isostearate, stearyl glycyrrhetate, tocopheryl acetate, bisabolol, methylparaben, propylhydroxybenzoate, butylated hydroxytoluene, a fragrance;

phase B: water, glycerin, propylene glycol, butylene glycol, panthenol, dipropylene glycol, allantoin, betaine, carbomer, aminomethyl propanol;

and C phase: ginseng radix extract, radix Sophorae Flavescentis extract, phenoxyethanol, Bonnat Spirulina extract, dipotassium glycyrrhizinate, lactobacillus/semen glycines fermented product extract, and bis-diethoxydiol cyclohexane 1, 4-dicarboxylate.

Wherein ethylhexyl palmitate, cyclomethicone, caprylic/capric triglyceride, oleyl erucate, shea butter, dimethicone, cyclohexasiloxane, C12-15 alcohol benzoate, squalane are oils and fats;

the compound of polyglyceryl-3-methylglucose distearate, glyceryl stearate and PEG-100 stearate is an emulsifier;

hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer, a compound of isohexadecane, polysorbate-60 and sorbitan isostearate, ammonium acryloyldimethyl taurate/VP copolymer and carbomer are thickening agents;

glycerin, butanediol, panthenol, dipropylene glycol, and betaine are moisturizers;

propylene glycol, bis-diethoxydiol cyclohexane 1, 4-dicarboxylate are permeation enhancers;

aminomethyl propanol is a pH adjusting agent;

lactobacillus/soy fermentation product extract, Bonnate Spirulina extract, and allantoin are skin conditioners.

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

dipotassium glycyrrhizinate is a skin whitening agent; stearyl glycyrrhetinate and bisabolol are soothing agents;

butylated hydroxytoluene, lycopene, tocopheryl acetate are antioxidants;

the essence is an aromatic; phenoxyethanol, methyl hydroxybenzoate and propyl hydroxybenzoate are antiseptic.

In the invention, the compound of glycerol stearate and PEG-100 stearate has the following types: ARLACEL 165;

hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer and a complex of isohexadecane and polysorbate-60 and sorbitan isostearate, the manufacturer: french Saybik Co.

Application of comparative examples 1 to 8

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

TABLE 4

TABLE 5

Skin elasticity test

Method for testing skin elasticity: the test principle is based on the principle of suction and stretching, where a negative pressure is generated on the skin surface to be tested to suck 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 transmitter and receiver of light, the ratio of which (the ratio of transmitted light to received light) is proportional to the depth of skin being absorbed, thus obtaining a time-dependent curve of the length of skin stretched.

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

The number of subjects was 33, the test period was 8 weeks, the test selected the repair creams of application examples 1 to 5 and the repair creams of application comparative examples 1 to 8 as test samples, 13 different areas were divided on the forearm of the subject, and the repair creams of application examples 1 to 5 and the repair creams of application comparative examples 1 to 8 were applied to the different areas on the inner side of the forearm, respectively, in the morning and evening of each day, in an amount of about 2mg/cm²And the position of application of each test sample was kept constant during the test period, and then the skin elasticity of the tested area before the test and at 8 weeks of use was measured, respectively, to further characterize the rate of change of skin elasticity (averaged), and the results of the specific rate of change of elasticity are shown in 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 change rate of elasticity, i.e., enhanced skin elasticity, and thus, the use of the ginseng extract and the sophora flavescens root extract is effective in improving skin aging.

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

The above examples of the present invention are merely examples for clearly illustrating the present invention and are not intended to limit the embodiments of the present invention. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. Any modification, equivalent replacement, and improvement made within the spirit and principle of the present invention should be included in the protection scope of the claims of the present invention.

Claims (10)

1. A collagenase inhibitor comprising: the collagenase inhibitor comprises a ginseng extract and a sophora flavescens root extract, wherein the ginseng extract is added in an amount of 51-97% and the sophora flavescens root extract is added in an amount of 3-49% based on the total mass of the collagenase inhibitor.

2. The collagenase inhibitor according to claim 1, wherein the mass ratio of the ginseng extract to the sophora flavescens root extract is 1.1-32: 1, preferably 2-30: 1, more preferably 3-28: 1, further preferably 4-25: 1, further preferably 5-22: 1, and further preferably 6-20: 1.

3. Collagenase inhibitor according to claim 1 or 2, characterised in that the collagenase is a interstitial collagenase.

4. A method of preparing a collagenase inhibitor according to any one of claims 1-3, comprising the step of mixing the components of a collagenase inhibitor.

5. A repair cream characterized by comprising the collagenase inhibitor according to any one of claims 1 to 3 and a penetration enhancer, wherein the collagenase inhibitor is added in an amount of 0.01 to 10% by mass of the total mass of the repair cream; the addition amount of the penetration enhancer is 0.01-10%.

6. The repair cream of claim 5, wherein the penetration enhancer comprises one or a combination of two or more of propylene glycol, bis-diethoxydiethylene glycol cyclohexane 1, 4-dicarboxylate and chitosan.

7. The repair cream of claim 5 or 6, further comprising one or a combination of more than two of a moisturizer, a thickener, a pH adjuster, a grease, a preservative, a skin conditioner, a skin whitener, an emulsifier, a soothing agent, an antioxidant, and a fragrance;

preferably, the addition amount of the humectant is 0.01-20% of the total mass of the repair cream; the addition amount of the thickening agent 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 conditioner is 0.01-5%; the addition amount of the allergy 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%.

8. The repair cream of claim 7 wherein the skin conditioning agent comprises one or a combination of two or more of a kelp extract, a fucus extract, a hydrolyzed collagen, a chlorella extract, allantoin, a lactobacillus/soy fermentation product extract, a mistletoe ginkgo leaf extract, a cogongrass rhizome extract, beta-glucan, palmitoyl tripeptide-5, acetyl hexapeptide-8, a cactus extract, a bonatea spirulina extract.

9. The repair cream according to claim 7 or 8, wherein the skin whitening agent comprises one or a combination of two or more of niacinamide, dipotassium glycyrrhizinate, magnolia sieboldii extract, kojic acid and its derivatives, arbutin and its derivatives, vitamin C; and/or the presence of a gas in the gas,

the soothing agent comprises one or more of Hamamelis virginiana water, bisabolol, stearyl glycyrrhetinate, centella asiatica extract, and rhizoma Zingiberis recens root extract.

10. A method of making a repair cream according to any one of claims 5 to 9, comprising the step of mixing the components of the repair cream.

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