CN113041179B - Moisturizing cream and preparation method thereof and collagenase inhibitor - Google Patents

Abstract

The invention provides a moisturizing cream, a preparation method thereof and a collagenase inhibitor. The moisturizing cream comprises a collagenase inhibitor and a penetration enhancer; the adding amount of the collagenase inhibitor is 0.01-10% based on the total mass of the moisturizing cream; the addition amount of the penetration enhancer is 0.01-10%; the collagenase inhibitor comprises a red pomegranate bark extract and a kuh-seng root extract, wherein the adding amount of the red pomegranate bark extract is 51-95% and the adding amount of the kuh-seng root extract is 5-49% based on the total mass of the collagenase inhibitor. The moisturizing cream disclosed by the invention is mild in formula, and can effectively improve skin elasticity, so that an anti-aging effect is achieved.

Description

Moisturizing cream and preparation method thereof and collagenase inhibitor

Technical Field

The invention relates to a moisturizing cream, a preparation method thereof and a collagenase inhibitor, 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 polypeptide and the retinol have certain irritation to skin, safety risk and other problems, and the invention firstly provides the moisturizing cream which contains the collagenase inhibitor and has excellent anti-aging effect.

Further, the invention also provides a collagenase inhibitor and a preparation method thereof, wherein the collagenase inhibitor can inhibit the activity of collagenase.

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

Solution for solving the problem

The invention provides a moisturizing cream, which comprises a collagenase inhibitor and a penetration enhancer; the adding amount of the collagenase inhibitor is 0.01-10% based on the total mass of the moisturizing cream; the addition amount of the penetration enhancer is 0.01-10%;

The collagenase inhibitor comprises a red pomegranate bark extract and a kuh-seng root extract, wherein the adding amount of the red pomegranate bark extract is 51-95% and the adding amount of the kuh-seng root extract is 5-49% based on the total mass of the collagenase inhibitor.

The moisturizing cream according to the present invention, wherein the mass ratio of the pomegranate rind extract to the kuh-seng extract is 1.1-19:1, preferably 2-18:1, more preferably 3.5-17:1, further preferably 4-16:1, further preferably 4.5-15.5:1, still further preferably 5-15:1.

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

The moisturizing cream of the present invention further comprises one or a combination of two or more of moisturizers, thickeners, pH adjusters, oils, emulsifiers, skin conditioners, skin whiteners, skin soothing agents, antioxidants, chelators, preservatives, and fragrances;

preferably, the humectant is added in an amount of 0.01 to 20% based on the total mass of the moisturizing cream; the addition amount of the thickener is 0.02-5%; 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 emulsifier is 0.01-5%; the addition amount of the skin conditioning agent is 0.01-5%; the addition amount of the skin whitening 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 chelating agent is 0.01-1%; the addition amount of the preservative is 0.01-1.5%; the addition amount of the aromatic is 0.01-1%.

The moisturizing cream of the invention, wherein the skin conditioner comprises one or more than two of crambe-weed seed oil, trehalose, brown algae extract, palmitoyl oligopeptide, magnesium aspartate, ceramide 2, kelp extract, allantoin, hydrolyzed collagen, lactobacillus/soybean fermentation product extract, ulva extract, colloidal oat flour, beta-glucan, pansy extract, creosote extract, PEG-10 brassica sterols and chlorella fermentation product.

The moisturizing cream of the present invention, wherein the skin whitening agent comprises one or a combination of more than two of nicotinamide, magnolia sieboldii extract, kojic acid and its derivatives, arbutin and its derivatives, and vitamin C; and/or

The sensitivity-relieving agent comprises one or more of Hamamelis virginiana water, centella asiatica extract, ginger root extract, bisabolol, dipotassium glycyrrhizinate and stearyl glycyrrhetinate.

The present invention also provides a collagenase inhibitor comprising: the extract of the pomegranate rind and the extract of the kuh-seng root are added in an amount of 51-95% and 5-49% based on the total mass of the collagenase inhibitor.

The collagenase inhibitor according to the present invention, wherein the mass ratio of the pomegranate rind extract to the kuh-seng extract is 1.1 to 19:1, preferably 2 to 18:1, more preferably 3.5 to 17:1, further preferably 4 to 16:1, still further preferably 4.5 to 15.5:1, still further preferably 5 to 15:1.

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.

ADVANTAGEOUS EFFECTS OF INVENTION

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

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

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

Drawings

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

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 shows a graph of the content of extract of guava skin in relation to 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 extract of the pomegranate rind and the extract of the kuh-seng root are added in an amount of 51-95% and 5-49% 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 guava skin 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 pomegranate rind extract to the kuh-seng extract is 1.1-19:1, preferably 2-18:1, more preferably 3.5-17:1, further preferably 4-16:1, further preferably 4.5-15.5:1, still further preferably 5-15:1. When the mass ratio of the extract of the pomegranate rind to the extract of the kuh-seng 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 extract of the pomegranate rind and the extract of the kuh-seng root are uniformly mixed by adopting a conventional mixing mode.

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 to test the anti-aging effect.

The purpose of the collagenase inhibitor of the present invention is to inhibit collagenase activity, for example: inhibiting the activity of interstitial collagenase, but not the expression of collagenase.

Extract of pomegranate rind

Punica granatum (Punica granatum l.) is Punica granatum (Punica) deciduous shrubs or arbors. The baldry peninsula to iran and its neighboring areas are planted in temperate and tropical regions worldwide. The cultivation is carried out in both north and south China, and the planting area is large in Jiangsu, henan and other places. The pomegranate is one of the pomegranates.

The red pomegranate rind has rich chemical substances, such as tannins, alkaloid compounds, flavonoids, amino acids, organic acids and the like, which have pharmacological and health-care effects on human bodies, and can be used for treating insect expelling, hemostasis, dysentery, toothache and the like. The pericarpium Granati extract is rich in pericarpium Granati polyphenols, including ellagitannin, ellagic acid catechol, chlorogenic acid, etc. These substances have antioxidant, free radical scavenging, sun screening, and skin whitening effects.

In the present invention, the addition amount of the extract of guava skin is 51-95% by weight based on the total mass of the collagenase inhibitor. When the addition amount of the pomegranate rind extract is 51-95%, collagenase activity can be effectively inhibited.

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 5-49% based on the total mass of the collagenase inhibitor. When the adding amount of the kuh-seng root extract is 5-49%, the collagenase activity can be effectively inhibited.

<Second aspect>

In a second aspect the present invention provides a moisturizing cream comprising a collagenase inhibitor according to the first aspect of the present invention and a penetration enhancer; the moisturizing cream provided by the invention can inhibit the activity of collagenase, especially the activity of interstitial collagenase by adding a proper content of collagenase inhibitor, so that the moisturizing cream provided by the invention has an excellent anti-aging effect and can improve skin elasticity. In order to promote the absorption of collagenase inhibitors by the skin, the moisturizing 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 moisturizing 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 addition amount of the penetration enhancer is 0.01-10% based on the total mass of the moisturizing 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 moisturizing 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 moisturizing cream also comprises one or more than two of a humectant, a thickener, a pH regulator, grease, an emulsifier, a skin conditioning agent, a skin whitening agent, a sensitivity-relieving agent, an antioxidant, a chelating agent, a preservative and a fragrance; the moisturizing cream disclosed by the invention has mild formula composition, and the efficacy of the collagenase inhibitor disclosed by the invention can be fully exerted. Specifically:

the addition amount of the moisturizing agent is 0.01-20% based on the total mass of the moisturizing cream. When the addition amount of the humectant is 0.01-20%, the moisturizing effect can be achieved. In order to further exert the effect of the humectant, the humectant of the present invention may be added in an amount of 1 to 18%, 3 to 16%, 5 to 14%, 6 to 12%, for example: 2%, 3%, 6%, 8%, 10%, 12%, 15%, 17%, 19%, etc.

In the invention, the humectant comprises one or more than two of butanediol, panthenol, dipropylene glycol, glycerol polyacrylate, sodium hyaluronate and trehalose.

The addition amount of the thickener is 0.02-5% based on the total mass of the moisturizing cream. By adding a thickener, the consistency of the moisturizing cream of the present invention can be made appropriate. Preferably, the thickener of the present invention may be added in an amount of 0.05 to 4%, 0.1 to 3%, 1 to 3%, etc.

In the invention, the thickener comprises one or more than two of carbomer, xanthan gum, polydimethylsiloxane/vinyl polydimethylsiloxane cross-linked polymer, behenyl alcohol, polyacrylamide, ammonium acryloyldimethyl taurate/VP copolymer and hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer.

The addition amount of the pH regulator is 0.01-1% based on the total mass of the moisturizing cream. The pH value of the moisturizing 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 0.05 to 0.5%, may be 0.06 to 0.3%, etc. When the added amount of the pH adjustor is more than 1% or less than 0.01%, a moisturizing cream having a proper pH cannot be obtained.

In the present invention, the pH adjustor includes one or a combination of two or more of aminomethylpropanol, arginine, citric acid, sodium citrate, sodium hydroxide, potassium hydroxide, and the like.

The amount of the fat added is 10 to 30% by weight of the total mass of the moisturizing cream, and 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 moisturizing cream, evaporation of moisture on the surface of the skin 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 moisturizing cream is too greasy, and the use feeling is reduced.

In the present invention, the oil or fat includes one or a combination of two or more of isopropyl myristate, polydimethylsiloxane, cyclopentadimethylsiloxane, caprylic/capric triglyceride, oleyl erucate, hydrogenated polyisobutylene, shea butter, ethylhexyl palmitate, hydrogenated polydecene, cyclohexasiloxane, C20-24 alkyl polydimethylsiloxane, C13-14 isoparaffin, C12-15 alcohol benzoate, hydrogenated soybean oil, phytosterol, and olive oil unsaponifiable matter.

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 moisturizing cream, for example: may be 0.1-5%, 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.

In the present application, the emulsifier includes one or a combination of two or more of a complex of cetostearyl alcohol and cetostearyl glucoside, a complex of PEG-100 stearate and glyceryl stearate, a complex of sorbitan sesquioleate and isosteareth-20, PEG-10 campesterol, laureth-7, polyglycerol-3 methyl glucose distearate, PEG/PPG-10/1 polydimethylsiloxane, polyglycerol-3 diisostearate, glyceryl stearate, steareth-20, cetyl polyether-20, polysorbate-60.

In addition, in the present application, it is preferable to use one or a combination of two or more of a complex of cetostearyl alcohol and cetostearyl glucoside, a complex of PEG-100 stearate and glyceryl stearate, a complex of sorbitan sesquioleate and isosteareth-20 as an emulsifier, so that the emulsification of the moisturizing cream is more sufficient and the stability is excellent.

The emulsifying system of the present application 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.

In order to further improve the efficacy of the moisturizing cream of the present application, the moisturizing cream of the present application further comprises the skin conditioner. The skin conditioner is added to calm the skin, so that the facial skin injury red swelling can be relieved to a certain extent, and the generation of wrinkles can be reduced. The effective components in the skin conditioner can penetrate deep into skin and be absorbed by skin, so as to improve skin state.

The addition amount of the skin conditioning agent is 0.01-5% based on the total mass of the moisturizing cream. The skin conditioner may be added in an amount of 0.01-4%, 0.5-3%, 0.9-2%, etc. When the addition amount of the skin conditioning agent is less than 0.01%, the content is too low to achieve corresponding effects; when the addition amount of the skin conditioner is more than 5%, the cost is excessively high.

The skin conditioner comprises one or more than two of deep sea crambe seed oil, trehalose, brown algae extract, palmitoyl oligopeptide, magnesium aspartate, ceramide 2, kelp extract, allantoin, hydrolyzed collagen, lactobacillus/soybean fermentation product extract, ulva extract, colloidal oat flour, beta-glucan, pansy extract, carrageenan extract, PEG-10 brassica napus sterol and chlorella fermentation product.

The colloidal oat flour can reduce the irritation of the moisturizing cream, can relieve the itching symptom of the skin, and is used for diminishing inflammation, relieving itching and relieving erythema.

The skin whitening agent is added in an amount of 0.01-5% based on the total mass of the moisturizing cream. The skin whitening agent may be added in an amount of 0.01-4%, 0.1-3%, 0.4-2%, etc. 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, 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 moisturizing cream; for example, 0.5%, 1%, 2%, 3%, 4% and the like are possible. When the addition amount of the allergy-relieving agent is less than 0.01%, the allergy-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.

The sensitivity-relieving agent comprises one or more of Hamamelis virginiana water, centella asiatica extract, ginger root extract, bisabolol, dipotassium glycyrrhizinate and stearyl glycyrrhetinate.

The moisturizing cream of the present invention may further be appropriately added with an antioxidant and a chelating agent. In general, the antioxidant is added in an amount of 0.01 to 2% based on the total mass of the moisturizing cream; the addition amount of the chelating agent is 0.01-1%. The antioxidant can be one or more of vitamin E, tocopheryl acetate, butylhydroxytoluene, lycopene, and ascorbyl ethyl ether. The chelating agent may be disodium EDTA and/or tetrasodium EDTA, and the like.

In addition, the moisturizing cream also comprises a preservative and a fragrance. The addition amount of the preservative is 0.01-1.5% based on the total mass of the moisturizing cream; the addition amount of the aromatic is 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.

<Third aspect of the invention>

A third embodiment of the present invention provides a method for preparing the moisturizing cream of the second embodiment, including the step of mixing the components of the cosmetic.

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

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

2. Adding water, part of humectant, part of penetration enhancer, chelating agent, rest of thickener, pH regulator and part of skin conditioner 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 60-65deg.C, adding the rest humectant, homogenizing, and stirring;

5. cooling to 40-45deg.C, adding collagenase inhibitor, residual penetration enhancer, skin whitening agent, residual antiseptic and residual skin conditioner, and stirring;

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

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

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.

The guava skin extract was 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

Providing extract of pericarpium Granati as collagenase inhibitor. The pomegranate rind extract was dissolved in 5 groups of deionized water of different volumes to obtain 5 groups of test solutions, the concentrations of the 5 groups of test solutions being 4000 μg/mL, 3200 μg/mL, 2400 μg/mL, 1600 μg/mL, 800 μg/mL, respectively. The logarithmic mass concentration of the extract of guava skin 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. 2 below.

Examples 1 to 5

Providing extract of pericarpium Granati and extract of radix Sophorae Flavescentis as collagenase inhibitor. The collagenase inhibitor is obtained by mixing the extract of the pomegranate rind and the extract of the kuh-seng root in a mass ratio of 1:2 (example 1), 1:1 (example 2), 5:1 (example 3), 12:1 (example 4) and 15:1 (example 5).

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 content (mass%) of the extract of the pomegranate rind and the extract of the kuh-seng in the collagenase inhibitor is shown in table 1 below, and the logarithmic mass concentration of the collagenase inhibitor is 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. In general, casein is used as substrate, 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, after the casein precipitate is removed by centrifugation or filtration, the supernatant is taken, and Na is used 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:

(1) taking 1 test tube, adding deionized water 0.25mL and collagenase 0.25mL (32U/mL) respectively, then adding substrate casein solution 0.5mL (1.0%) and immediately mixing uniformly, carrying out water bath heat preservation for 10min at 37 ℃, then adding trichloroacetic acid solution 1mL (6.5%) and uniformly mixing, standing for 10min, centrifuging at 10000rpm for 5min, taking supernatant fluid sample 0.5mL in the test tube in 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; the supernatant 1 of the test group was obtained, and absorbance was measured at a wavelength of 650nm and designated as A1.

(2) Taking 1 test tube, adding deionized water 0.25mL and collagenase 0.25mL (32U/mL) respectively, then adding trichloroacetic acid solution 1mL (6.5%) and immediately mixing, carrying out water bath heat preservation at 37 ℃ for 10min, then adding substrate casein solution 0.5mL (1.0%) and mixing uniformly, standing for 10min, centrifuging at 10000rpm for 5min, taking supernatant fluid sample 0.5mL in the test tube in 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.

(3) 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%) 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%) 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 samples in the 35 test tubes are taken into other 35 test tubes respectively, 0.5mL (mass concentration: 10%) of sodium bicarbonate test solution is added respectively, and shaking is carried out 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.

(4) 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%) of trichloroacetic acid solution is added and mixed evenly immediately, after the temperature is kept in a water bath at 37 ℃ for 10min, then 0.5mL (1.0%) of substrate casein solution is added and mixed evenly, after standing for 10min, centrifugation is carried out at 10000rpm for 5min, 0.5mL of supernatant samples in the 35 test tubes are taken into other 35 test tubes respectively, 0.5mL (mass concentration: 10%) of sodium bicarbonate test solution is added respectively, and shaking is carried out 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 respective extracts of the red pomegranate bark extract (comparative examples 1 to 5) and the kuh-seng root extract (comparative examples 6 to 10) were calculated. And combining the logarithmic mass concentration-collagenase activity inhibition ratio relationship graph (fig. 1 and 2), and obtaining the corresponding mass concentration (IC) when the inhibition ratio of the pericarpium Granati extract is 50% by conversion _50A ) And the mass concentration (IC) corresponding to 50% inhibition rate of radix Sophorae Flavescentis extract _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 relationship graph (figure 3) of logarithmic mass concentration and collagenase activity inhibition ratio, and calculating the equivalent inhibition ratio (50%) of the combined action of the pericarpium Granati extract and radix Sophorae Flavescentis extract by conversion _50a ) The method comprises the steps of carrying out a first treatment on the surface of the When the equivalent inhibition rate (50%) is generated by the combined action of the pomegranate rind 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 the extract of the pomegranate rind and the extract of the kuh-seng root can be evaluated by using an 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 pomegranate rind 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 pomegranate rind extract when the equivalent inhibition rate (50%) is generated by the combined action of the pomegranate rind extract and the kuh-seng root extract;

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

Wherein γ=1, representing that the extract of the red pomegranate rind and the extract of the kuh-seng show a simple additive effect; gamma is less than 1, and the extract of the pomegranate rind and the extract of the kuh-seng show a synergistic effect, and the smaller the gamma value is, the stronger the synergistic effect is; gamma > 1 is that the extract of the pomegranate rind and the extract of the kuh-seng show antagonism, and the bigger the gamma value is, the bigger the antagonism is.

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 thus the extract of pericarpium Granati and the extract of radix Sophorae Flavescentis may exhibit excellent synergistic effects.

Application examples 1 to 5

According to the contents (mass percentages) of the respective components in the formulations of the moisturizing creams of application examples 1 to 5 in the following table 4, moisturizing creams were prepared 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 80-85 ℃ to fully dissolve the phase A raw material;

2. adding phase B into emulsifying pot, stirring and heating to 80-85deg.C to dissolve thoroughly;

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

4. cooling to 60 ℃, adding phase C, homogenizing and stirring uniformly;

5. cooling to 42 ℃, adding phase D and stirring uniformly;

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

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

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

Phase A: cyclopentadimethicone, hydrogenated polyisobutene, caprylic/capric triglyceride, ethylhexyl palmitate, complex of cetyl stearyl alcohol and cetostearyl glucoside, dimethicone/vinyl dimethicone crosspolymer, behenyl alcohol, complex of PEG-100 stearate and glyceryl stearate, dimethicone, complex of sorbitan sesquioleate and isosteareth-20, tocopheryl acetate, methylparaben, propylparaben, butylhydroxytoluene, stearyl glycyrrhetinate, fragrances;

and B phase: water, glycerol, propylene glycol, butylene glycol, dipropylene glycol, disodium EDTA, xanthan gum, carbomer, potassium hydroxide, panthenol, colloidal oat flour, sodium hyaluronate, trehalose;

And C phase: glycerol polyacrylate;

and D phase: lactobacillus/soybean fermentation product extract, pericarpium Granati extract, magnolia sieboldii extract, radix Sophorae Flavescentis extract, herba Chenopodii extract, phenoxyethanol, and bis-diethoxydiglycol cyclohexane 1, 4-dicarboxylic acid ester.

The extract of pericarpium Granati and radix Sophorae Flavescentis used in the formula is collagenase inhibitor;

cyclopentadimethicone, hydrogenated polyisobutene, caprylic/capric triglyceride, ethylhexyl palmitate, and dimethicone as oils;

the complex of cetostearyl alcohol and cetostearyl glucoside, the complex of PEG-100 stearate and glyceryl stearate, the complex of sorbitan sesquioleate and isosteareth-20 are used as emulsifying agents;

tocopheryl acetate and butylated hydroxytoluene are antioxidants; stearyl glycyrrhetinate is a allergy-relieving agent;

glycerin, butylene glycol, dipropylene glycol, panthenol, sodium hyaluronate, and glycerin polyacrylate as humectant;

colloidal oat flour, trehalose, lactobacillus/soybean fermentation product extract, carrageenan extract as skin conditioner;

disodium EDTA is a chelating agent; potassium hydroxide is a pH adjustor;

Xanthan gum, carbomer, polydimethylsiloxane/vinyl polydimethylsiloxane cross-linked polymer and behenyl alcohol are used as thickening agents;

methyl hydroxybenzoate, propyl hydroxybenzoate and phenoxyethanol are used as preservatives;

propylene glycol, bis-diethoxydiglycol cyclohexane 1, 4-dicarboxylate as a permeation enhancer;

the magnolia sieboldii extract is a whitening agent; the essence is aromatic.

In the present invention, a complex of cetostearyl alcohol and cetostearyl glucoside is produced by the manufacturer: sibirk Co; brand number: montanov 68;

PEG-100 stearate and glycerol stearate, manufacturer: company trademark of Heda: arlael 165;

complex of sorbitan sesquioleate and isosteareth-20, manufacturer: the Bobby company; brand number: BAREMUL ^TM ML。

Comparative examples 1 to 8 were used

Moisturizing creams were prepared according to the contents (mass percentages) of each component in the moisturizing cream formulations of application comparative examples 1 to 8 in the following table 5, and in the same manner as 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 moisturizing creams of application examples 1 to 5 and the moisturizing creams of application comparative examples 1 to 8 were selected as test samples, 13 different areas were divided on the forearms of the subjects, the moisturizing creams of application examples 1 to 5 and the moisturizing creams of application comparative examples 1 to 8 were applied to different areas on the inner sides of the forearms in the morning and evening every day, and the application amount was about 2mg/cm ² The smearing position of each test sample in the test period is kept unchangedThe skin elasticity of the test area before and after 8 weeks of use was then measured, and the rate of change of skin elasticity was further characterized, and the results of specific elastic change rate (averaged) 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 rate of change in elasticity, i.e., skin elasticity is enhanced, and thus, the use of the extract of guava skin and the extract of kuh-seng root can effectively improve skin aging.

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 (6)

1. A moisturizing cream comprising a collagenase inhibitor and a penetration enhancer; the adding amount of the collagenase inhibitor is 0.01-10% based on the total mass of the moisturizing cream; the addition amount of the penetration enhancer is 0.01-10%;

the collagenase inhibitor comprises a red pomegranate bark extract and a kuh-seng root extract, wherein the adding amount of the red pomegranate bark extract is 51-95% and the adding amount of the kuh-seng root extract is 5-49% based on the total mass of the collagenase inhibitor; and, in addition, the processing unit,

The mass ratio of the pomegranate rind extract to the kuh-seng root extract is 10-12:1;

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

2. The moisturizing cream of claim 1, further comprising one or a combination of two or more of a humectant, a thickener, a pH adjuster, a grease, an emulsifier, a skin conditioner, a skin whitening agent, a sensitivity-soothing agent, an antioxidant, a chelating agent, a preservative, and a fragrance.

3. The moisturizing cream of claim 2, wherein the moisturizing agent is added in an amount of 0.01-20% based on the total mass of the moisturizing cream; the addition amount of the thickener is 0.02-5%; 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 emulsifier is 0.01-5%; the addition amount of the skin conditioning agent is 0.01-5%; the addition amount of the skin whitening 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 chelating agent is 0.01-1%; the addition amount of the preservative is 0.01-1.5%; the addition amount of the aromatic is 0.01-1%.

4. The moisturizing cream of claim 3, wherein the skin conditioning agent comprises one or more of deep sea crambe seed oil, trehalose, brown algae extract, palmitoyl oligopeptide, magnesium aspartate, ceramide 2, kelp extract, allantoin, hydrolyzed collagen, lactobacillus/soybean fermentation product extract, ulva extract, colloidal oat flour, beta-glucan, pansy extract, carrageenan extract, PEG-10 brassica sterols, chlorella fermentation product.

5. The moisturizing cream of claim 3, wherein the skin whitening agent comprises one or a combination of two or more of nicotinamide, magnolia sieboldii extract, kojic acid, arbutin, and vitamin C; and/or

The sensitivity-relieving agent comprises one or more of Hamamelis virginiana water, centella asiatica extract, ginger root extract, bisabolol, dipotassium glycyrrhizinate and stearyl glycyrrhetinate.

6. A moisturizing cream according to any one of claims 1 to 5 wherein the collagenase is interstitial collagenase.