CN112402287A

CN112402287A - Efficient soothing anti-allergy repair polypeptide combination and application thereof

Info

Publication number: CN112402287A
Application number: CN202011236017.9A
Authority: CN
Inventors: 黄毅; 邢海英; 刘志国; 虞新友
Original assignee: Zhejiang Baitai Biology Co ltd
Current assignee: Zhejiang Baitai Biology Co ltd
Priority date: 2020-11-09
Filing date: 2020-11-09
Publication date: 2021-02-26

Abstract

The invention discloses a high-efficiency relieving and anti-allergy repairing polypeptide combination and application thereof, and provides the high-efficiency relieving and anti-allergy repairing polypeptide combination which comprises acetyl heptapeptide-4, oligopeptide, palmitoyl tripeptide-8, palmitoyl tetrapeptide-7, heptapeptide-6, butanediol 10-30%, glycerol, water, carbomer and sodium lactate, wherein the pH range is 4.0-6.0, the polypeptides in the combination can effectively synergize, and the polypeptide combination has a more effective anti-allergy repairing effect and an obvious synergistic effect compared with a single polypeptide and a part of polypeptide combinations thereof. The anti-allergy repair of the invention covers three aspects of a skin sensitivity forming mechanism, has a brand-new barrier repair mechanism, effectively regulates and controls sensory nerve hyperreaction and reduces inflammation and aging, and is an ideal and comprehensive anti-allergy repair product.

Description

Efficient soothing anti-allergy repair polypeptide combination and application thereof

Technical Field

The invention relates to the technical field of cosmetics. More specifically, the invention relates to a high-efficiency soothing anti-allergy repair polypeptide combination and application thereof.

Background

With the increasing environmental pollution and mental stress, the incidence rate of sensitive skin in various countries of the world is gradually increased, which seriously affects the quality of life of people, and especially in developed countries such as Japan and America, the skin sensitivity has become a social problem affecting human health. According to incomplete statistics, the population of the global self-sensation sensitive skin is more and more, wherein the male accounts for 38% and the female accounts for 61%. It follows that skin care for sensitive muscles has a great market demand.

Sensitive skin, also known as sensitive skin syndrome, is skin that is poorly tolerated, highly reactive or susceptible to sensitization. It has been reported that approximately 70% of the population thinks of themselves having the characteristics of sensitive skin, and 50% of them show symptoms of skin allergy. It mainly occurs on the face, and is manifested by subjective symptoms such as burning, stabbing pain, itching and tightness of skin when being stimulated by physical, chemical and mental factors, and sometimes accompanied by objective signs such as erythema, scales and telangiectasia.

Sensitive skin is generally considered to be the interaction of factors in a body and outside, and the main theory aiming at the forming mechanism of the sensitive skin at present is that the barrier function of the skin is damaged, the sensory signal transmission of the sensitive skin is further enhanced, the tolerance threshold is reduced, the reaction to external weak stimulation is excessive, simultaneously different cell types of the skin are stimulated and activated to induce and release proinflammatory cytokines and chemokines, and inflammatory cell infiltration causes a series of sensitive symptoms of the skin.

With the increasing population of people with sensitive muscles and the enhancement of people's awareness of skin care, cosmetics with anti-allergy efficacy are increasingly valued by people, and the addition of anti-allergy active ingredients in cosmetic formulations also becomes a common means. The natural plant extract component is the core additive of the current anti-allergy component. Comprises chamomile, purslane, centella, gentian, saffron, lavender and the like; however, the action mechanism of the plant extract is not clear, and further intensive research is needed; in addition, due to the influence of plant sources, extraction modes and other factors, impurities are not easy to distinguish, the quality of batches is difficult to control, the extraction process is complex, the cost is high, and certain application limitations exist.

As an active substance with physiological regulation function, the exact action mechanism and the extremely high biological safety of the biological polypeptide are increasingly applied to improving common problems of sensitive skin, such as neurogenic inflammation, pruritus, stabbing pain, desquamation and the like.

The polypeptides which have been studied for anti-allergic action are acetyl tetrapeptide-15, palmitoyl tripeptide-8, acetyl dipeptide-1 cetyl ester, palmitoyl tetrapeptide-7, etc. Meanwhile, the combination of the polypeptides is reported, the skin neurogenic infection is relieved from action targets of different points, and the polypeptide has more effective antiallergic effect than a single polypeptide and has a certain synergistic effect. However, the polypeptide combination only aims at regulating the hyperreaction of the nerve sense organ and reducing the formation of proinflammatory factors, has no relation to the barrier damage formed by sensitive skin, and has certain efficacy limitation on the relaxation and repair of the sensitive skin.

The skin barrier can effectively prevent the invasion of external harmful factors and the loss of nutrient substances in the body, and the barrier function is damaged, thereby being an important reason for skin sensitivity. People with thinner stratum corneum are more susceptible to chemical irritation. The weak stratum corneum has a strong skin penetration ability and irritants are more easily introduced to cause inflammatory reactions in the skin. And as a microbial flora attached to the skin, is the first barrier to the reaction of the skin surface.

Currently, microbial skin care is one of the hot spots in cosmetic research. One of the most important functions of microbiota and epidermal skin microbiota is that it acts as a protective barrier to the skin, which can occur by different mechanisms. Competition for bacteria by direct competition for space and nutrients, beneficial bacteria can lead to the exclusion of potentially harmful microorganisms from the skin surface. From a physical point of view, the microflora also contributes to strengthening the skin barrier. The interaction of microorganisms with the epidermis can enhance the TJs function of keratinocytes by activating TLRs signals. This will help to enhance the barrier function of the skin and prevent further invasion by harmful microorganisms.

Studies have shown that sensitive skin samples contain high levels of proteases, which are released by Staphylococcus aureus (s. aureus, SA) and can disrupt the skin barrier. The staphylococcus aureus can secrete a plurality of exotoxins with superantigen characteristics, can induce and cause repeated inflammation, the carrying rate of children and adults with healthy skin is less than 5.00 percent, and multiple studies show that the staphylococcus aureus at the skin lesion of sensitive skin is remarkably increased, and is a factor for causing skin sensitivity.

Therefore, the skin micro-ecology can be improved by controlling staphylococcus aureus, the balance of the micro-ecology of the first barrier layer of the skin is promoted, and the skin barrier is comprehensively repaired from inside to outside aiming at the repair of inflammatory injuries of the stratum corneum and the dermis layer of the skin.

According to the sensitive skin forming mechanism, the concept of skin micro-ecological balance and dermal matrix remodeling is innovatively introduced, the skin micro-ecology is improved by controlling staphylococcus aureus on the surface of the skin from the aspect of skin micro-ecology, the balance of the skin first barrier micro-ecology is promoted, and meanwhile, the skin is comprehensively repaired from inside to outside aiming at the inflammatory injury repair of the skin cuticle and the dermis. Meanwhile, according to a large number of experiments, the polypeptide for reducing the skin nerve source reaction and the polypeptide for reducing the skin immunoreaction caused by inflammation are combined, and the excellent anti-allergy repair effect of the polypeptide is further verified by more comprehensive polypeptide combination aiming at all angles of sensitive skin.

Disclosure of Invention

Aiming at the defects of the prior art, the invention provides a polypeptide combination with high-efficiency, relieving and anti-allergy repairing effects, and the anti-allergy repairing effect is superior to that of the common anti-allergy agent components in the market; compared with the traditional anti-allergy polypeptide combination, the invention realizes the excellent anti-allergy repair effect by more comprehensive polypeptide combination, has definite action mechanism, extremely high safety and biological activity compared with an implant anti-allergy agent, can obviously improve the anti-allergy repair application effect in cosmetics, and has obvious significance.

In order to achieve the purpose, the invention provides the following technical scheme:

a high-efficiency soothing anti-allergy repairing polypeptide combination is characterized in that: the high-efficiency soothing and anti-allergy repairing polypeptide composition comprises, by weight, 40.001-3% of acetyl heptapeptide, 10.001-5% of oligopeptide, 80.001-3% of palmitoyl tripeptide, 70.0001-3% of palmitoyl tetrapeptide, 60.001-3% of heptapeptide, 10-30% of butanediol, 20-70% of glycerol, 10-30% of water, 0.05-5% of carbomer and 0.05-5% of sodium lactate, wherein the pH range of the high-efficiency soothing and anti-allergy repairing polypeptide composition is 3.0-8.0.

Preferably, the pH of the hypersensitive repair polypeptide combination is in the range of 4.0-6.0.

Preferably, the application of the high-efficiency soothing and anti-allergy repairing polypeptide combination in the skin care product.

The application of the polypeptide combination for relieving and anti-allergy repair in the preparation of cosmetics is characterized in that the polypeptide combination can be added into various skin care products including essences, freeze-dried powder, cream, gel, facial masks and the like, and the effects of the product are relieving, anti-allergy and repair.

The application of the soothing and anti-allergy repairing polypeptide combination in the preparation of cosmetics is characterized in that the high-efficiency soothing and anti-allergy repairing polypeptide combination is added into a skin care product or a medical product with an anti-allergy and soothing effect, wherein the mass fraction of the high-efficiency soothing and anti-allergy repairing polypeptide combination is 0.1-50%.

An application of a high-efficiency relieving and anti-allergy repairing polypeptide composition in a medical product.

The application of the polypeptide combination for relieving and anti-allergy repairing in preparing cosmetics can be applied to relieving the characteristic of skin sensitivity, relieving erythema, pruritus, numbness words and skin tightness caused by sensitivity, relieving contact dermatitis, eczema and the like, and helping to quickly repair damaged skin and establish a healthy skin barrier from inside to outside.

In summary, according to the above technical solution, in the present invention:

the acetyl heptapeptide-4 can inhibit the colonization of staphylococcus aureus by promoting the adhesion of beneficial bacteria of the skin, improve the immune response of the skin, enhance the integrity of a physical barrier and improve the defense system of the skin. The microbial group of urban skin is healthier, and the barrier protection of the skin is enhanced.

Oligopeptide-1 can reduce the influence of inflammation on skin, effectively promote epidermal regeneration, repair skin barrier and reshape the biochemical function of skin.

Palmitoyl tripeptide-8 has affinity similar to a-MSH, is easily combined with MC1-R, and in keratinocytes, palmitoyl tripeptide-8 effectively reduces inflammatory mediators induced and generated by UVB by combining and activating MC1-R receptors, and simultaneously can reduce the release of neuromediator Substance P, regulate the hyperreaction of skin sensory nerve signals, and prevent neurodermatitis symptoms such as edema and red blood filaments.

Palmitoyl tetrapeptide-7 can regulate the secretion capacity of interleukin IL-6 by mimicking a fragment in immunoglobulin IgG, thereby reducing the damage of inflammation to the skin.

Heptapeptide-6 can be remodeled by a dermal matrix, increase collagen and reduce skin aging caused by inflammation.

Compared with the prior art, the invention has the beneficial effects that: compared with the traditional plant anti-allergy agent, the polypeptide has exact action mechanism and extremely high safety when being used for cosmetics, the anti-allergy repair combination covers three aspects of a skin sensitivity forming mechanism, a brand-new barrier repair mechanism can effectively regulate and control sensory nerve hyperreaction and reduce inflammation and aging, the effect is more complete compared with that of the existing polypeptide combination product, and a large number of experimental argumentations prove that the polypeptide is an ideal and comprehensive anti-allergy repair product and has a predictable effect on bioactive polypeptide in the field of anti-allergy, relieving and repairing cosmetic effects.

Drawings

FIG. 1 is a graph of skin erythema decay rates for different samples on a subject;

FIG. 2 is a graph of the skin pruritus decay rate for different samples for a subject;

FIG. 3 is a calculation formula for measurement of hyaluronidase inhibition.

Detailed Description

The examples of a polypeptide combination of the invention which is highly effective in soothing and anti-allergy repair are further illustrated:

the invention will now be further illustrated with reference to the following examples:

examples 1-4 a high potency soothing anti-allergy repair polypeptide combination, as shown in table 1.

TABLE 1

The configuration method comprises the following steps: adding carbomer in a formula amount into water and butanediol, stirring to mix uniformly, standing and soaking for 24h, stirring and homogenizing for 5-10 min to obtain a uniform particle-free solution, sequentially adding polypeptide uniformly dispersed in polysorbate-20 at 40 deg.C below according to the examples and comparative examples, stirring uniformly, and adjusting pH to about 5.0 with sodium lactate.

Comparative examples 1-5, single polypeptides, using a combination of five single polypeptide components as comparative examples, are shown in table 2.

TABLE 2

The configuration method comprises the following steps: adding carbomer in a formula amount into water and butanediol, stirring to mix uniformly, standing and soaking for 24h, stirring and homogenizing for 5-1 min to obtain a uniform particle-free solution, sequentially adding polypeptide uniformly dispersed in polysorbate-20 at 40 deg.C below according to the examples and comparative examples, stirring uniformly, and adjusting pH to about 5.0 with sodium lactate.

Comparative examples 6-10, some of the polypeptides were combined and other polypeptides with the same potency were combined as comparative examples, as shown in table 3. (acetyl heptapeptide-4 and heptapeptide-6 as A and B, red moieties represent C and D) as shown in Table 3.

TABLE 3

Test example 1 Hyaluronidase inhibition test

Hyaluronidase is a specific lyase of hyaluronic acid, a participant in allergic reactions, and has a strong correlation with histamine release by mast cells. Whether a substance has anti-allergy activity can be judged by utilizing the activity inhibition rate of hyaluronidase, and the higher the activity inhibition rate of hyaluronidase is, the stronger the anti-allergy effect of the substance is reflected, and the weaker the anti-allergy effect of the substance is, otherwise.

1 test sample

The samples prepared in examples 1 to 4 and comparative examples 1 to 10 were dissolved and diluted to 1% with ultrapure water as samples to be tested.

Meanwhile, 1-2 commercially available anti-sensitivity agents are selected and dissolved and diluted to 1% by ultrapure water to be used as experimental reference samples.

Reference sample 1: glycerophosphoinositide choline salt;

reference sample 2: hydroxyphenyl propionamide benzoic acid

2 solution preparation

2.1 acetic acid buffer solution (PH = 5.6)

Weighing 1.155 mL of glacial acetic acid, diluting to 100 mL, uniformly mixing, and taking 4.8 mL of glacial acetic acid as A solution; weighing 2.72 g of sodium acetate crystal, adding water to dissolve the crystal, fixing the volume to 100 mL, uniformly mixing, and taking 45.2 mL of the solution as a B solution; the solution A, B was mixed and made up to 100 mL with water. Precisely measuring pH, and adjusting to 5.6 with solution A or B.

2.2 Hyaluronidase solutions

Hyaluronidase was dissolved in acetic acid buffer solution to a final working concentration of 1250U/mL.

2.3 sodium hyaluronate solution

Sodium hyaluronate 5 mg is weighed and placed in a beaker, 10 mL of acetic acid buffer solution is added to obtain 0.5 mg/mL of sodium hyaluronate solution.

2.4 Ellisib reagents

0.8 g of p-dimethylaminobenzaldehyde is weighed out and dissolved in 15 mL of concentrated hydrochloric acid and 15 mL of absolute ethanol.

2.5 sodium carbonate solution

5.3 g of anhydrous sodium carbonate is weighed and placed in a beaker, and the volume is adjusted to 50 mL by pure water, so as to obtain 1 mol/L sodium carbonate solution.

2.6 acetylacetone solution

3.5 mL of acetylacetone was dissolved in 50 mL of 1.0 mol/L sodium carbonate solution, and the solution was prepared before use.

3 assay of hyaluronidase Activity inhibition

3.1 test procedure

Taking 0.1 m L CaCl2 solution (0.25 mmol/L) and 0.5 mL hyaluronidase solution, and performing water bath constant temperature culture at 37 deg.C for 20 min; adding 0.5 mL of sample solution to be tested, and keeping the temperature for 20 min; adding 0.5 mL sodium hyaluronate solution (0.5 mg/m L), culturing in water bath at 37 deg.C for 30 min, taking out, and standing at room temperature for 5 min; adding 0.1 mL of NaOH solution (0.4 mol/L) and 0.5 mL of acetylacetone solution, heating in a boiling water bath for 15 min, and immediately transferring to an ice water bath to cool for 5 min; 1.0 mL of Ellisib reagent is added dropwise, and diluted with 3.0 mL of absolute ethanol, the mixture is placed at room temperature for 20min for color development, and the absorbance value at the wavelength of 540 nm is measured by a spectrophotometer.

3.2 analysis of results

The calculation formula of the sample for measuring the hyaluronidase inhibition rate is shown in the third figure:

4 the results are shown in Table 4

As can be seen from Table 4, the polypeptide compositions of examples 1 to 4 of the present invention and the single component and the complex polypeptide corresponding to comparative examples 1 to 10 all have a certain inhibitory effect on hyaluronidase, whereas the inhibitory effect on hyaluronidase of the compositions of examples 1 to 4 of the present invention is more pronounced than that of comparative examples 1 to 10

The anti-allergy effect of the composition is more obvious after scientific compounding.

The results of examples 1-4 and 6-10 are selected for analysis and comparison, and it can be seen that the combination of the acetyl heptapeptide-4 and the heptapeptide-6 has a significant effect on improving the hyaluronidase inhibition rate, and the hyaluronidase inhibition rate of the acetyl heptapeptide-4 and the heptapeptide-6 is not as good as that of examples 1-4 by replacing any component of the combination or combining the acetyl heptapeptide-4 and the heptapeptide-6 with other polypeptides. The polypeptide combination can effectively realize synergy, has more effective hyaluronidase inhibition effect than single polypeptide and partial polypeptide combination thereof, shows obvious synergistic effect, and can be expected to be applied to anti-allergy repair products.

Test example 2 skin prick relief test (skin sensitivity test by histamine phosphate stimulation)

Taking the polypeptide compositions of example 1 and comparative example 10 for experimental comparison, and taking water as a blank placebo control to evaluate the itching-relieving and redness-reducing effects;

organizing 20 volunteers, respectively wet-coating 20uL of 1% histamine phosphate in a region of 3 x 3cm of the arm skin of the volunteer, waiting for the skin to become red and itchy, and recording the time; then, 20uL of each of the 0.1% diluted sample of example 1 and the sample of comparative example 10 and water were added dropwise to the test area, and the time to the resolution of the red itch was recorded.

Testing parts: inside of arm

And (3) testing environment: temperature: 20 ℃ to 22 ℃, humidity: 40 to 60 percent

Reference for skin erythema: GB17149.2-1997 determination of the reaction degree of the tested part;

the itching feeling refers to the evaluation and the countermeasure of the skin itching degree of a skin patient;

the results are shown in Table 5

TABLE 5

The test result shows that the soothing and anti-allergy repair polypeptide combination has obvious effect of relieving erythema and pruritus caused by the skin irritation of histamine phosphate, and the skin sensitization phenomenon caused by the histamine phosphate is completely eliminated in 10min by containing 0.1% of the polypeptide combination in the example 1. The soothing effect is obviously superior to that of the comparative example 10, and the application of the combination of the acetyl heptapeptide-4 and the heptapeptide-6 obviously improves the soothing and anti-allergy repairing effect of the combination application of the acetyl heptapeptide-4 and the heptapeptide-6 and other anti-allergy polypeptides, and has obvious synergistic effect on the application of other anti-allergy polypeptides.

Test example 3 skin prick relief test (skin sensitivity test caused by histamine hydrochloride stimulation)

Taking the commercially available glycerophosphoinositide choline salt in example 2 for experimental comparison, and taking water as a blank placebo control to evaluate the itching relieving and redness reducing effects;

organizing 20 volunteers, respectively wet-coating 20uL of 0.8% histamine hydrochloride on a 3 x 3cm area of the arm skin of the volunteer, waiting for the skin to become red and itchy, and recording the time; then, 20uL each of the 0.1% diluted sample of example 2 and the glycerophosphoinositide choline salt sample and water was added dropwise to the test area and the time to resolution of the red itch was recorded.

Testing parts: inside of arm

the evaluation of skin itching degree of skin patients and countermeasures for itching feeling are shown in reference test example 2;

the test scores of all the subjects were averaged, and the decay rate of the skin erythema of the subjects was calculated by the histamine-applied reagent in the different samples as shown in fig. 1, and it can be seen that the erythema eliminating effect of the 0.1% anti-allergic repair peptide was stronger in sample No. 1 after sample application for 20 min.

Test results show that the soothing and anti-allergy repairing polypeptide combination has obvious effect of relieving erythema and pruritus caused by skin stimulation by histamine hydrochloride, and the effect of reducing the erythema and the pruritus by containing 0.1% of the polypeptide combination of the example 2 is obviously better than that of the commercially available glycerol phosphoinositide choline salt, so that the soothing and anti-allergy repairing polypeptide combination can effectively realize synergistic effect, has more effective anti-allergy repairing effect than a single polypeptide and part of polypeptide combinations thereof, and shows obvious synergistic effect. The anti-allergy repair of the invention covers three aspects of a skin sensitivity forming mechanism, has a brand-new barrier repair mechanism, effectively regulates and controls sensory nerve hyperreaction and reduces inflammation and aging, and is an ideal and comprehensive anti-allergy repair product.

The above description is provided for further details of the present invention with reference to specific modified embodiments, and it should not be considered that the present invention is limited to these specific embodiments, and it should be understood that those skilled in the art may make several simple deductions or substitutions without departing from the spirit of the present invention, and all such alternatives are deemed to fall within the scope of the present invention.

Claims

1. A high-efficiency, soothing and anti-allergy repairing polypeptide combination is characterized in that: the high-efficiency soothing and anti-allergy repairing polypeptide composition comprises, by weight, 40.001-3% of acetyl heptapeptide, 10.001-5% of oligopeptide, 80.001-3% of palmitoyl tripeptide, 70.0001-3% of palmitoyl tetrapeptide, 60.001-3% of heptapeptide, 10-30% of butanediol, 20-70% of glycerol, 10-30% of water, 0.05-5% of carbomer and 0.05-5% of sodium lactate, wherein the pH range of the high-efficiency soothing and anti-allergy repairing polypeptide composition is 3.0-8.0.

2. The combination of highly effective soothing anti-allergy repair polypeptides according to claim 1, wherein: the pH range of the high-efficiency relieving and anti-allergy repairing polypeptide combination is 4.0-6.0.

3. The use of a high potency soothing anti-allergy repair polypeptide combination of any one of claims 1-2 in a skin care product.

4. Use of the high efficiency soothing anti-allergy repairing polypeptide combination according to claim 3 in the preparation of cosmetics, wherein: the polypeptide composition can be added into various skin care products in various dosage forms, including essence, freeze-dried powder, cream, gel, facial mask and the like, and the product has the effects of relieving, resisting allergy and repairing.

5. Use of the high efficiency soothing anti-allergy repairing polypeptide combination according to claim 3 in the preparation of cosmetics, wherein: the high-efficiency, soothing and anti-allergy repairing polypeptide composition is added into a skin care product or a medical product with an anti-allergy and soothing effect, wherein the mass fraction of the high-efficiency, soothing and anti-allergy repairing polypeptide composition is 0.1-50%.

6. The use of a highly effective soothing and anti-allergy repairing polypeptide combination as claimed in any one of claims 1 to 2 in medical products.

7. The use of the high potency soothing anti-allergy restoring polypeptide combination of claim 6 in the preparation of a cosmetic, wherein: the skin care product can be applied to relieving the sensitive characteristics of skin, relieving erythema, pruritus, numbness words and skin tightness caused by sensitivity, relieving contact dermatitis, eczema and the like, and helping to quickly repair damaged skin and establish a healthy skin barrier from inside to outside.