CN115670965A - Anti-inflammatory composition for skin effective in inhibiting IL-8, TNF-alpha and IL-6 - Google Patents
Anti-inflammatory composition for skin effective in inhibiting IL-8, TNF-alpha and IL-6 Download PDFInfo
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- lysine polypeptide
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Images
Abstract
The invention provides a skin anti-inflammatory composition capable of effectively inhibiting IL-8, TNF-alpha and IL-6, which comprises palmitoyl tetrapeptide-7, palmitoyl pentapeptide-4 and arginine/lysine polypeptide, can simultaneously and efficiently inhibit the secretion of inflammatory factors IL-8, TNF-alpha and IL-6, enables a compound composition to achieve the effects of resisting bacteria and inflammation, resisting allergy, repairing damaged cells and effectively removing acnes, is used for preparing cosmetics, medicines or health products, can improve the self-repairing capability of cells, resist external air pollution and play a role in relieving acnes, thereby realizing long-term skin quality improvement, and having better stability, stronger dissolubility, longer shelf life, greenness, safety, no stimulation and no need of preservatives.
Description
The present application claims application number 2021105342058 filed 2021, 5/17, and claims priority of the title "a skin anti-inflammatory composition effective in inhibiting IL-8, TNF-a and IL-6".
Technical Field
The invention relates to the technical field of skin care products, in particular to a skin anti-inflammatory composition, and particularly relates to a skin anti-inflammatory composition which can effectively inhibit IL-8, TNF-alpha and IL-6 and has an acne-removing effect.
Background
With the influence of factors such as human social development, environmental pollution, rapid increase of living pressure and the like, the skin problems of urban personnel are gradually exposed, dull, colored spots, acne, comedo, sensitivity and the like, so that beauty and skin care are more and more emphasized by people, and besides pursuing excellent efficacy, safety and stability are also important points of attention of people.
The particles in the air have great damage to the skin, so that pores can be blocked, the skin becomes dark and rough, the skin can be stimulated, discomfort such as sensitive skin, redness, dryness and the like can be caused, and symptoms such as skin itch, skin allergy and the like can be caused. Air pollution and ultraviolet rays are considered as one of the main factors causing skin pollution and hair pollution. Over 80% of consumers worldwide believe that skin absorbs airborne contaminants.
Aiming at the skin problems caused by air pollution, acne and the like, a plurality of inflammatory cytokines are the root causes of the problems. Among many inflammatory cytokines, TNF-alpha, IL-8, IL-1 beta, IL-6 and the like play a major role, wherein TNF-alpha and IL-8 are the most closely related to skin protection, antibiosis and anti-inflammation, and IL-6 is related to acne removal.
TNF-alpha (tumor necrosis factor) is the earliest and most important inflammatory mediator in the inflammatory response, and can activate neutrophils and lymphocytes, increase permeability of vascular endothelial cells, regulate metabolic activity of other tissues and promote synthesis and release of other cytokines.
IL-8 can stimulate chemotaxis of neutrophils, T lymphocytes and eosinophils, promote degranulation of neutrophils, release elastase, damage endothelial cells, and lead microcirculation blood flow to be stagnated and tissues to be necrotic, thereby causing organ function damage.
In sebaceous gland cells, androgen can be converted into more active Dihydrotestosterone (DHT) under the action of 5 a-reductase, and further high expression of inflammatory factor IL-6 is stimulated, so that the capacity of inducing acne is enhanced. Therefore, the inhibition of the inflammatory factor IL-6 can also inhibit acne, so as to achieve the effect of treating the acne.
However, the existing products capable of effectively inhibiting inflammatory factors and effectively removing acnes generally have the defects of good effect but not mild enough and safety, or mild but not satisfactory effect.
Therefore, the need for a skin anti-inflammatory composition which is safer, milder, can inhibit various inflammatory factors and can effectively remove acne is urgent.
Disclosure of Invention
Aiming at the problems, the invention provides an anti-inflammatory composition for skin, which comprises palmitoyl tetrapeptide-7, palmitoyl pentapeptide-4 and arginine/lysine polypeptide, can efficiently inhibit the expression of inflammatory factors IL-8, TNF-alpha and IL-6 at the same time, so that the compound composition achieves the effects of resisting bacteria, diminishing inflammation, resisting allergy, repairing damaged cells and effectively removing acnes.
In one aspect, the invention provides an anti-inflammatory composition for skin, which mainly comprises three components, wherein the first component is palmitoyl tetrapeptide-7, the second component is palmitoyl pentapeptide-4, and the third component is arginine/lysine polypeptide.
Palmitoyl Tetrapeptide-7 (Palmitoyl Tetrapeptide-7), molecular formula: c 34 H 62 N 8 O 7 CAS number: 221227-05-0 is a synthetic peptide composed of four amino acids, the amino acid sequence of which is Pal-Gly-Gln-Pro-Arg, abbreviated as Pal-GQPR, belongs to one of signal peptides, is a fragment of immunoglobulin IgG, can act on glial cells and fibroblasts through signal stimulation, can delay and inhibit the release of excessive inflammatory factor interleukin IL-6, thereby inhibiting inappropriate inflammatory reaction and glycosylation damage, and maintaining the balance of cytokines in the skin to test the protection of the skin, thereby lightening wrinkles and tightening the skin.
Palmitoyl Pentapeptide-4 (Palmitoyl Pentapeptide-4) with the molecular formula of C 39 H 75 N 7 O 10 CAS number: 214047-00-4, the amino acid sequence of which is Pal-Lys-Thr-Thr-Lys-Ser, abbreviated as Pal-KTTKS, is a Matrikine signal peptide, can activate skin fibroblasts, synthesize, repair and rebuild extracellular matrix, promote the synthesis of collagen, fibronectin and polysaccharide, have definite anti-aging effect, can effectively improve skin roughness, reduce the number of fine lines, reduce the depth and area of wrinkles and the like, and have the characteristics of mildness and no irritation.
Arginine/lysine Polypeptide (Arginine/lysine Polypeptide), CAS No.: 31014-78-5, is a polymeric polypeptide (L-Arginine) rich in Arginine and lysine, has good compatibility with skin, is not allergic, has good anti-aging and anti-wrinkle effects, has low irritation to skin and eyes, and has good emulsifying, antistatic, dispersing, and dirt removing effects.
The inventor finds that when three components, namely palmitoyl tetrapeptide-7, palmitoyl pentapeptide-4 and arginine/lysine polypeptide, are compounded, the synergistic effect is obvious in the mild anti-inflammatory aspect, the capability of inhibiting secretion of inflammatory factors IL-8, TNF-alpha and IL-6 can be greatly improved, the acne removing effect is good, the anti-inflammatory effect is mild, free of stimulation, green and safe, good in stability and good in solubility, no preservative is needed, and the skin care cream can be used for improving skin quality for a long time.
Further, the volume ratio of the three components is as follows: palmitoyl tetrapeptide-7: palmitoyl pentapeptide-4: arginine/lysine polypeptide = 1-10%, 1-10% and 0.5-10%.
Researches prove that when the three components of the palmitoyl tetrapeptide-7, the palmitoyl pentapeptide-4 and the arginine/lysine polypeptide are in a certain proportion range, the composition has better synergistic effect.
In another aspect, the present invention provides the use of a composition for the manufacture of a formulation for inhibiting the secretion of inflammatory factors, said anti-inflammatory skin care composition comprising three components, wherein the first component is palmitoyl tetrapeptide-7, the second component is palmitoyl pentapeptide-4, and the third component is an arginine/lysine polypeptide.
Further, the inflammatory factors include IL-8, IL-6 and TNF- α.
Further, the volume ratio of the three components is as follows: palmitoyl tetrapeptide-7: palmitoyl pentapeptide-4: arginine/lysine polypeptide = 1-10%, 1-10% and 0.5-10%.
In some embodiments, the formulation comprises a skin care, pharmaceutical, or nutraceutical.
In a further aspect, the invention provides the use of a composition in the preparation of a formulation for inhibiting one or more of IL-8, IL-6 or TNF- α.
Further, the volume ratio of the three components is as follows: palmitoyl tetrapeptide-7: palmitoyl pentapeptide-4: arginine/lysine polypeptide = 1-10%, 1-10% and 0.5-10%.
In another aspect, the invention provides an application of a composition in preparing an acne-removing preparation, wherein the anti-inflammatory skin care product composition comprises three components, wherein the first component is palmitoyl tetrapeptide-7, the second component is palmitoyl pentapeptide-4, and the third component is arginine/lysine polypeptide.
Further, the anti-inflammatory composition for skin achieves the effect of removing acne by inhibiting the secretion of inflammatory factors IL-8, IL-6 and TNF-alpha.
Further, the volume ratio of the three components is as follows: palmitoyl tetrapeptide-7: palmitoyl pentapeptide-4: arginine/lysine polypeptide = 1-10%, 1-10% and 0.5-10%.
In some embodiments, the formulation comprises a skin care, pharmaceutical, or nutraceutical.
In some embodiments, the skin care product, pharmaceutical product or health care product prepared from the anti-inflammatory skin care composition comprising palmitoyl tetrapeptide-7, palmitoyl pentapeptide-4 and arginine/lysine polypeptide according to the present invention may be appropriately blended with various ingredients, such as powder ingredients, moisturizers, thickeners, metal ion masking agents, pigments, pH regulators, skin nutrients, vitamins, preservatives, antioxidants, antioxidant aids, perfumes, etc., which are generally blended in the fields of cosmetics and quasi drugs, as needed, within a range that does not impair the effects of the present invention.
The invention provides a skin anti-inflammatory composition, which has the following beneficial effects:
1. can effectively inhibit the secretion of inflammatory factors IL-8, TNF-alpha and IL-6 at the same time, and has obvious synergistic effect;
2. can improve the self-repairing ability of cells, resist the pollution of outside air and play the effect of relieving acne, thereby realizing the long-term skin improvement;
3. the stability is better, and the shelf life is longer;
4. the solubility is enhanced, and no solubilizer is added;
5. is more green and safe, has no stimulation and does not need preservative.
Drawings
FIG. 1 is a schematic representation of the effect of palmitoyl tetrapeptide-7, palmitoyl pentapeptide-4, arginine/lysine polypeptide, and combinations thereof in inhibiting the inflammatory factor IL-6 in example 2.
Detailed Description
The present invention is described in further detail below with reference to examples, which are intended to facilitate the understanding of the present invention without limiting it in any way.
EXAMPLE 1 protective Capacity of different compositions against IL-8 and TNF-alpha caused by air pollution
Inoculation: normal human epidermal keratinocytes were inoculated at an inoculation density of 1E 4/well into 96-well plates and incubated overnight in an incubator (37 ℃, 5% CO2, 95% RH).
Preparing liquid: the test article working solution was prepared according to the experimental design (see table 1).
The adopted palmitoyl tetrapeptide-7, palmitoyl pentapeptide-4 and arginine/lysine polypeptide are 98% pure powder, and are prepared into a solution for experiment, wherein the specific mixture ratio is as follows:
palmitoyl tetrapeptide-7 solution: 100ppm =100mg/L mass concentration +10-20% glycerol +1-5% tween +0.5-1% preservative (phenoxyethanol) +74-88.5% water;
palmitoyl pentapeptide-4 solution: 50ppm =50mg/L mass concentration +10-20% glycerol +1-5% tween +0.5-5% preservative (phenoxyethanol) +74-88.5% water;
arginine/lysine polypeptide solution: 1000ppm =1000mg/L mass concentration +1-5% hexanediol +95-99% water.
Air dust stimulation: according to the experimental concrete design of table 1, when the cell plating rate in the 96-well plate reaches 40% -50%, the corresponding drug solution is added according to the volume ratio for group stimulation, 0.1mg/mL of air dust is added into each well (no air dust is added into blank control wells), and 3 multiple wells are arranged in each group. The culture was continued in an incubator (37 ℃, 5% CO2, 95% RH).
Collecting cell supernatant: after 24h of culture, the cell culture supernatant was collected in an EP tube and stored frozen at-80 ℃ in a refrigerator after collection.
The influence of each sample group on IL-8 and TNF-alpha was analyzed by ELISA assay, and the inhibition of each sample group on IL-8 and TNF-alpha is shown in Table 1.
TABLE 1 inhibition of the secretion of the inflammatory factors IL-8 and TNF-alpha in keratinocytes caused by air pollution by different combinations of active substances
As can be seen from Table 1, the inhibition rate of 1% palmitoyl tetrapeptide-7 alone on IL-8 is only 9.21%, and the inhibition rate on TNF-alpha reaches 11.91%; 3% of palmitoyl pentapeptide-4 alone hardly inhibits TNF-alpha, and the inhibition rate of IL-8 only reaches 5.82%; even if the content of the palmitoyl tetrapeptide-7 is increased to 3 percent and the content of the palmitoyl pentapeptide-4 is increased to 5 percent, the inhibition rate of IL-8 and TNF-alpha is not obviously improved. While the inhibition rate of the 5% arginine/lysine polypeptide alone on IL-8 and TNF-alpha is higher than that of palmitoyl tetrapeptide-7 and palmitoyl pentapeptide-4, but is only about 25%.
When 1% palmitoyl tetrapeptide-7 and 3% palmitoyl pentapeptide-4 are adopted for compounding, the inhibition rates of IL-8 and TNF-alpha are only slightly improved, but the effect is still not ideal; similarly, 1% palmitoyl tetrapeptide-7 or 3% palmitoyl pentapeptide-4 is compounded with 5% arginine/lysine polypeptide respectively, so that the inhibition rates of IL-8 and TNF-alpha are improved to a certain extent, but the ideal effect of inhibiting the expression of IL-8 and TNF-alpha is still difficult to achieve.
When 1% palmitoyl tetrapeptide-7, 3% palmitoyl pentapeptide-4 and 5% lysine/arginine polypeptide are jointly compounded, the inhibitor plays a very good role in inhibiting IL-8 and TNF-alpha, the inhibition rate of IL-8 and TNF-alpha is close to 80%, and the effect is very obvious. The three components of the palmitoyl tetrapeptide-7, the palmitoyl pentapeptide-4 and the arginine/lysine polypeptide have obvious synergistic effect on the inhibition of the inflammatory factors IL-8 and TNF-alpha.
However, the proportional relationship among palmitoyl tetrapeptide-7, palmitoyl pentapeptide-4 and lysine/arginine polypeptide also has certain influence on the effect of inhibiting IL-8 and TNF-alpha secretion, and when 3% palmitoyl tetrapeptide-7, 5% palmitoyl pentapeptide-4 and 5% arginine/lysine polypeptide are adopted, the effect of inhibiting inflammatory factors IL-8 and TNF-alpha is further improved to reach 99.18% and 97.34% respectively.
Example 2 synergistic Effect of palmitoyl tetrapeptide-7, palmitoyl pentapeptide-4, and arginine/lysine polypeptide in inhibiting the inflammatory factor IL-6
Acne is a disease caused by multiple factors, local androgen metabolism is one of the most main causes, and excessive androgen can cause the volume of sebaceous glands to be increased and sebum secretion to be increased, the duct of the pilosebaceous glands is abnormal in keratinization, sebum excretion is not smooth, lipid embolism is formed, and acne is caused. In sebaceous gland cells, androgen can be converted into more active Dihydrotestosterone (DHT) under the action of 5 a-reductase, and further high expression of inflammatory factor IL-6 is stimulated, so that the capacity of inducing acne is enhanced. Therefore, the inhibition of the inflammatory factor IL-6 can inhibit the acne and achieve the effect of treating the acne.
This example compares the inhibition of the inflammatory factor IL-6 with a single component and a composition, respectively.
The main experimental process is as follows: raw264.7 mouse macrophage cells were normally cultured in DMEM medium containing 5% of CO2 at 37 ℃ in 10% FBS. When the cells grew to 90% density, they were treated as 8X10 5 The kit is inoculated on a 96-well plate at a density of/ml, samples with different concentrations are added for respective treatment for 24 hours after the materials are adhered to the wall for 8 hours, the samples are divided into a blank control group (a normal group), an LPS (an induction group), an LPS + positive control group (80 mu M dexamethasone) and an LPS + sample group, and corresponding test samples are added, wherein the sample groups are respectively 3% of palmitoyl tetrapeptide-7, 5% of palmitoyl pentapeptide-4 and 5% of arginine/lysine polypeptide; and 3% of palmitoyl tetrapeptide-7 and 5% of palmitoyl pentapeptide-4; 3% of palmitoyl tetrapeptide-7 and 5% of arginine/lysine polypeptide; 5% of palmitoyl pentapeptide-4 and 5% of arginine/lysine polypeptide; 3% of palmitoyl tetrapeptide-7, 5% of palmitoyl pentapeptide-4 and 5% of arginine/lysine polypeptide; mixing the single components or composition in the manner of preparation according to example 1, directly mixing, at 37 deg.C, 5% of CO2, and culturing under saturated humidity 24h, taking supernatant to detect, and repeating each group for 3 times. The test results are shown in fig. 1.
As can be seen from FIG. 1, the secretion of inflammatory factor IL-6 by Raw264.7 cells is obviously up-regulated after LPS treatment, and the amount of IL-6 is inhibited after the positive control dexamethasone treatment. Palmitoyl pentapeptide-4 has no obvious inhibition effect on the inflammatory factor IL-6, and palmitoyl tetrapeptide-7 has lower inhibition effect on the inflammatory factor IL-6 but is lower than that of positive control dexamethasone; the inhibition effect of the compound of the palmitoyl tetrapeptide-7 and the palmitoyl pentapeptide-4 on the inflammatory factor IL-6 is not obviously different from that of the compound of the palmitoyl tetrapeptide-7 used alone, but is still lower than that of the positive control dexamethasone; arginine/lysine polypeptide has obvious inhibition effect on inflammatory factor IL-6; when the palmitoyl tetrapeptide-7 or palmitoyl pentapeptide-4 is compounded with arginine/lysine polypeptide, the effect of inhibiting the inflammatory factor IL-6 is still not obviously different compared with the effect of singly using the arginine/lysine polypeptide; however, the inhibition rate of the composition compounded by the palmitoyl tetrapeptide-7, the palmitoyl pentapeptide-4 and the arginine/lysine polypeptide is obviously higher than the effect of singly using the arginine/lysine polypeptide and is obviously stronger than that of positive control dexamethasone (P is less than 0.01), which indicates that the three components of the palmitoyl tetrapeptide-7, the palmitoyl pentapeptide-4 and the arginine/lysine polypeptide have obvious synergistic action on the inhibition of the inflammatory factor IL-6.
Example 3 Long-term storage stability Studies of palmitoyl tetrapeptide-7, palmitoyl pentapeptide-4, and arginine/lysine polypeptide compositions
In this example, different sample solutions are prepared as shown in table 2, and a long-term storage stability study is performed, where the stability test refers to placing the sample solution in a thermostat at 48 ℃ for 3 months, observing whether the sample solution has abnormal phenomena such as turbidity and deterioration, and comparing whether the stability-examined sample solution is different from a newly-prepared sample solution. Because arginine/lysine polypeptide is sometimes unstable among palmitoyl tetrapeptide-7, palmitoyl pentapeptide-4 and arginine/lysine polypeptide, whether a sample solution is different from a newly formulated sample solution is evaluated by detecting the content of arginine/lysine polypeptide in the sample solution, wherein the arginine/lysine polypeptide is detected by the following method: integrating HPLC peak areas; while examining the shelf life of the sample solution. The results are shown in Table 2.
TABLE 2 Long-term stability study of different actives
As can be seen from Table 2, the stability of the single arginine/lysine polypeptide solution is not high, the content is obviously reduced after long-term high-temperature storage, 11.3% of deviation exists, and the quality guarantee period is shorter and is only 12 months; and after the palmitoyl tetrapeptide-7, the palmitoyl pentapeptide-4 and the arginine/lysine polypeptide are combined, the stability of the arginine/lysine polypeptide can be obviously improved, the content of the arginine/lysine polypeptide is always stable after long-term high-temperature storage, and the shelf life is prolonged to be more than 36 months.
Example 4 antibacterial synergy Studies of palmitoyl tetrapeptide-7, palmitoyl pentapeptide-4, and arginine/lysine polypeptide compositions
In this example, aqueous solutions were prepared according to table 3, and mixed with various antiseptic solutions, and sampled for microscopic examination every 7, 14, 21, and 42 days, to compare the bacteriostatic properties.
TABLE 3 study of the efficacy of different active ingredients
As can be seen from Table 3, the individual palmitoyl tetrapeptide-7, palmitoyl pentapeptide-4, arginine/lysine polypeptide, and the combination of palmitoyl tetrapeptide-7 and palmitoyl pentapeptide-4 have poor bacteriostatic properties, and a preservative is required to help bacteriostasis; after the arginine/lysine polypeptide is compounded with the preservative, the composite has slight bacteriostasis and synergism on bacteria after two weeks; after the palmitoyl tetrapeptide-7, the palmitoyl pentapeptide-4 and the arginine/lysine polypeptide are compounded, the antibacterial performance can be obviously enhanced, no preservative is required to be added, and the use is safer and more environment-friendly.
Example 5 anti-acne efficacy of palmitoyl tetrapeptide-7, palmitoyl pentapeptide-4, and arginine/lysine polypeptide compositions.
In this example, 10 groups of sample solutions as described in table 5 were used to perform the acne treatment efficacy test, and 300 healthy and acne-affected volunteers were recruited and screened and randomly divided into 10 groups of 30 persons, and 10 groups of samples were tested. The age of the volunteers is mainly concentrated on 18-30 years, and 77% of the volunteers have more than 5 pox growing amount per month. Any cosmetics or external medicines can not be used for 2-3 days before the tested part. Before the experiment, the volunteers were required to clean their faces. In the experiment, each group of volunteers applied the corresponding sample 2 times every morning and evening, each time according to 1mg/cm 2 The dosage is uniformly coated. After 3d and 14d use, questionnaires were performed. The results of the acne treatment are shown in table 4.
TABLE 4 questionnaire for anti-acne efficacy of human skin
As can be seen from table 4, sample group 10 has the best acne removing effect, sample group 9 times, and sample groups 9 and 10 are significantly better than sample groups 1 to 8, so sample group 10 is preferred as the best combination.
Although the present invention is disclosed above, the present invention is not limited thereto. Various changes and modifications may be effected by one skilled in the art without departing from the spirit and scope of the invention, as defined in the appended claims.
Claims (10)
1. An anti-inflammatory composition for skin comprising three components, wherein the first component is palmitoyl tetrapeptide-7, the second component is palmitoyl pentapeptide-4, and the third component is arginine/lysine polypeptide.
2. The composition of claim 1, wherein the volume ratio of the three components is: palmitoyl tetrapeptide-7: palmitoyl pentapeptide-4: arginine/lysine polypeptide = 1-10%, 1-10% and 0.5-10%.
3. The application of a composition in preparing a preparation for inhibiting the secretion of inflammatory factors is characterized in that the anti-inflammatory skin care product composition comprises three components, wherein the first component is palmitoyl tetrapeptide-7, the second component is palmitoyl pentapeptide-4, and the third component is arginine/lysine polypeptide.
4. The use of claim 3, wherein said inflammatory factors comprise IL-8, IL-6 and TNF- α.
5. Use according to claim 4, wherein the volume ratio of the three components is: palmitoyl tetrapeptide-7, palmitoyl pentapeptide-4, arginine/lysine polypeptide = 1-10%, and 0.5-10%.
6. Use of a composition in the preparation of an agent that inhibits one or more of IL-8, IL-6 or TNF- α.
7. Use according to claim 6, wherein the volume ratio of the three components is: palmitoyl tetrapeptide-7, palmitoyl pentapeptide-4, arginine/lysine polypeptide = 1-10%, and 0.5-10%.
8. The application of the composition in preparing the acne-removing preparation is characterized in that the anti-inflammatory skin care product composition comprises three components, wherein the first component is palmitoyl tetrapeptide-7, the second component is palmitoyl pentapeptide-4, and the third component is arginine/lysine polypeptide.
9. The use according to claim 8, wherein the anti-inflammatory composition for the skin achieves the effect of removing acne by inhibiting the secretion of the inflammatory factors IL-8, IL-6 and TNF- α.
10. Use according to claim 9, wherein the three components are present in a volume ratio of: palmitoyl tetrapeptide-7: palmitoyl pentapeptide-4: arginine/lysine polypeptide = 1-10%, 1-10% and 0.5-10%.
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| US20140086981A1 (en) * | 2011-03-25 | 2014-03-27 | José María GARCÍA ANTÓN | Pgc-1alpha-modulating peptides |
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