Polypeptide combined preparation for resisting allergy, relieving itching and treating skin inflammation related diseases

Abstract

The invention relates to the technical field of medicines, in particular to a polypeptide combined preparation with anti-allergy, itching-relieving, anti-inflammatory and repairing functions for treating skin inflammation related diseases. The polypeptide combined preparation is prepared from composite peptide and auxiliary materials, wherein the composite peptide is prepared from acyl dipeptide-1, palmitoyl tripeptide-8, hexapeptide-9, tetrapeptide-3, palmitoyl tripeptide-5, dipeptide-15 and acetyl heptapeptide-4. According to the polypeptide disclosed by the invention, through a trinity action mechanism of resisting allergy, relieving itching and repairing, the skin inflammation problem is improved from multiple dimensions of immune regulation, neural signal blocking, barrier strengthening and the like. Compared with a single component, the multi-target characteristic of the compound is safer and more efficient, the transdermal absorbability is high, and the compound is suitable for being developed into an external preparation (such as emulsion and essence) for skin disease treatment and daily nursing.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of polypeptide application, and particularly relates to a polypeptide combination preparation for treating skin inflammatory related diseases with anti-allergic itching, anti-inflammatory and repairing functions. BACKGROUND

[0002] Skin inflammatory related diseases, such as eczema and dermatitis, are often accompanied by symptoms such as itching, redness, pain, etc. Scratching can affect people's work and rest, and patients often have symptoms such as insomnia and irritability. When itching lasts for 6 weeks or more, it is chronic itching. Another clinical manifestation of chronic itching is the vicious cycle of scratching-itching-scratching, which further damages the skin barrier. On the basis of skin damage, microorganisms are more likely to multiply, causing further deterioration of the disease. Therefore, due to the slow course and easy recurrence of the disease, it often brings great physical and mental pain and psychological burden to patients, seriously affecting the quality of life of patients. Therefore, in recent years, it has attracted more and more attention.

[0003] Itching is widely divided into four main causes: skin disease, systemic cause, neuropathic cause and psychogenic cause. The commonly used treatment methods in clinical practice include hormone drugs and antihistamine drugs. Substances used for anti-inflammatory purposes include non-steroidal types such as ibuprofen and indomethacin, and steroidal types such as dexamethasone. However, these drugs have certain side effects and dependence, and itching will quickly recur after treatment is discontinued. At the same time, some drugs also contain antibiotics, which can inhibit beneficial bacteria in the body, leading to an imbalance in the bacterial flora; the side effects of traditional Chinese medicine treatment are small, but the effect is slow. In this regard, there is a high demand for the development of safe anti-inflammatory drugs with maximum effect and minimum side effects.

[0004] Polypeptide substances have good biological activity, high specificity and low toxicity, such as acetyl dipeptide-1 and palmitoyl tripeptide-8, which have anti-inflammatory, anti-wrinkle and skin barrier function maintenance effects, and can effectively relieve the symptoms of skin inflammatory related diseases. It is suitable for mild to moderate skin inflammatory related diseases. Chinese Patent Application 201911422748.X reports the use of polypeptides as active ingredients, plus excipients or auxiliary ingredients, including carboxypropyl methyl cellulose, asiaticoside, sodium hyaluronate, and allantoin, as a composition in anti-inflammatory and itching relief. The composition has anti-inflammatory and inhibitory and relieving effects on itching symptoms. Due to the complexity of the purification steps of peptides and the numerous processes, the cost of peptide preparation is relatively high, and single polypeptide has single function and is easily limited by factors such as enzymolysis and poor permeability, which is difficult to meet the treatment needs of complex skin problems. SUMMARY

[0005] The present application aims to overcome the deficiencies of the prior art, and provides a polypeptide composition for treating skin allergy, skin itching and common skin inflammation-related diseases.

[0006] In one aspect, the present application provides a polypeptide composition with anti-allergic, anti-itching, anti-inflammatory and repairing functions, which specifically comprises acetyl dipeptide-1, palmitoyl tripeptide-8, hexapeptide-9, tetrapeptide-3, palmitoyl tripeptide-5, dipeptide-15, acetyl heptapeptide-4 and excipients.

[0007] Preferably, the polypeptide composition comprises 0.2-0.8% acetyl dipeptide-1, 0.02%-0.07% palmitoyl tripeptide-8, 0.02%-0.1% hexapeptide-9, 0.08%-0.15% tetrapeptide-3, 0.05%-0.2% palmitoyl tripeptide-5, 0.05%-0.2% dipeptide-15, 0.02%-0.1% acetyl heptapeptide-4, and the rest is excipients.

[0008] Preferably, the polypeptide composition further comprises purslane extract, dipotassium glycyrrhizinate, ceramide NP, liposome and purified water.

[0009] Preferably, the polypeptide composition comprises 0.5-2% purslane extract, 0.1-0.3% dipotassium glycyrrhizinate, 1-3% ceramide NP and 0.5-2% liposome, and the rest is purified water.

[0010] Preferably, the liposome in the composition is phosphatidylcholine and cholesterol, and the mass ratio is 3:1.

[0011] Preferably, the polypeptide composition is wrapped by liposome.

[0012] In a preferred embodiment, the present application provides a preparation method of the polypeptide wrapped by the above-mentioned complex carrier as follows: Step 1: dissolve the complex peptide according to the prescription amount in phosphate buffer solution with pH 6.8 to prepare a solution with a polypeptide concentration of 10 mg / mL, and then add purslane extract, dipotassium glycyrrhizinate and ceramide NP and stir uniformly; Step 2: prepare liposome by using the film dispersion method; Step 3: add the polypeptide solution in step 1 to the liposome, stir to coat, freeze-dry to obtain the polypeptide composition.

[0013] In the second aspect, the present application provides a pharmaceutically acceptable external preparation prepared by combining the above-mentioned composition with pharmaceutically acceptable excipients.

[0014] Preferably, the external preparation is one of a gel, a cream, an emulsion, a face cream, an ointment, a paste, a lotion, a patch, a plaster, a film, a cataplasm, an aerosol or a spray.

[0015] In a third aspect, the present application also provides a polypeptide composition emulsion for treating skin inflammatory related diseases with anti-allergic, anti-itching and repairing functions, which comprises a polypeptide composition and pharmaceutically acceptable emulsion adjuvant.

[0016] Preferably, the emulsion adjuvant comprises squalane, glycerol, a pH regulator.

[0017] In a preferred embodiment, the present application provides a polypeptide composition emulsion with anti-allergic, anti-itching and repairing functions, and the content of the components is shown in Table 1. Table 1 Emulsion prescription with 10-20% polypeptide composition content

[0018] The pH regulator is preferably citric acid and triethanolamine. In a preferred embodiment, the present application provides a method for preparing the above polypeptide composition emulsion, which comprises the following steps: Step 1: Dissolve the complex polypeptide liposome in PBS (pH 6.8) to prepare a solution with a concentration of 5 mg / mL, add purified water and glycerol, and stir uniformly to prepare solution A; Step 2: Slowly drop squalane and capric acid triglyceride into solution A in a high-speed shearing machine to form a primary emulsion; Step 3: Transfer the primary emulsion to a high-pressure homogenizer, homogenize under high pressure, filter sterilize with a microporous membrane, and fill into a sterile container to obtain the polypeptide composition emulsion.

[0019] It is explained that most skin itching is caused by skin inflammation, so for skin itching, the synergistic effect of anti-itching and inflammation elimination is needed. Polypeptide is a natural product with anti-inflammatory and antibacterial effects, and is widely used in the field of cosmetics due to its no side effects. Polypeptide has a three-in-one mechanism of action of anti-allergic, anti-itching and repairing, and can improve skin inflammation problems from multiple dimensions such as immune regulation, nerve signal blocking and barrier strengthening. Its multi-target characteristics are safer and more efficient than single ingredients, and it has strong transdermal absorption, which is suitable for developing external preparations (such as emulsion and essence) for skin disease treatment and daily care.

[0020] The beneficial effects of the present application are: Compared with the prior art, the application overcomes the single function of a single polypeptide, and is limited by factors such as enzyme hydrolysis and poor permeability. The polypeptide synergistically enhances the therapeutic effect of anti-inflammatory, repair, and antibacterial multi-target joint action. The nano delivery technology breaks through the polypeptide penetration bottleneck, realizes efficient delivery and slow release, and the natural ingredient compound reduces the risk of irritation and enhances the barrier repair function. DETAILED DESCRIPTION

[0021] The application will be further described by examples. The test methods used in the following examples are conventional methods unless otherwise specified. The materials, reagents, etc. used are commercially available reagents and materials unless otherwise specified.

[0022] Example 1, a polypeptide composition is prepared according to the following prescription: Table 2 Composition prescription of Example 1 (100g)

[0023] The specific preparation process is as follows: Step 1: Dissolve the polypeptide according to the prescription amount in a phosphate buffer with a pH of 6.8 to prepare a polypeptide solution with a concentration of 10 g / mL. Add pure purslane extract, dipotassium glycyrrhizinate, and ceramide NP and stir until uniform. Step 2: Dissolve the liposome in 60 ml of a mixture of ethyl acetate / methanol (3:1, v / v) to prepare a lipid solution with a concentration of 20 mg / mL. Place the lipid solution in a rotary evaporator and evaporate under reduced pressure at 40°C and -0.08 MPa to form a uniform lipid film.

[0024] Step 3: Add the polypeptide-containing PBS solution prepared in Step 1 and purified water. Stir in a 40°C water bath for 30 min to completely hydrate the lipid film. Transfer to an ultrasonic disruptor and ultrasonicate under ice bath conditions (power 300 W, work 5 s / interval 5 s, total time 10 min) to form a liposome suspension.

[0025] Step 4: Extrude the liposome suspension through a polycarbonate membrane with a pore size of 100 nm (extrusion pressure 0.8 MPa, cycle number 5 times), and freeze-dry to obtain uniform liposomes.

[0026] Example 2, a polypeptide composition is prepared according to the following prescription: Table 3 Composition prescription of Example 2 (100g)

[0027] The specific preparation process is as follows: Step 1: The polypeptide was dissolved in phosphate buffer with pH 6.8 according to the prescription amount, and a solution with a polypeptide concentration of 10 mg / mL was prepared. The purslane extract, dipotassium glycyrrhizinate, and ceramide NP were added and stirred uniformly. Step 2: The liposome was dissolved in 25 ml of a mixed solvent of ethyl acetate / methanol (3:1, v / v) to prepare a lipid solution with a concentration of 20 mg / mL. The lipid solution was placed in a rotary evaporator and evaporated under reduced pressure at 40°C and -0.08 MPa to form a uniform lipid film.

[0028] Step 3: The polypeptide-containing PBS solution prepared in Step 1 was added, and purified water was added. The lipid film was completely hydrated by stirring in a 40°C water bath for 30 min. The mixture was transferred to an ultrasonic cell disruptor and ultrasonically treated (power 300 W, working 5 s / intermittent 5 s, total time 10 min) under ice bath conditions to form a liposome suspension.

[0029] Step 4: The liposome suspension was extruded through a polycarbonate membrane with a pore size of 100 nm (extrusion pressure 0.8 MPa, cycle number 5 times), and freeze-dried to obtain liposomes with uniform particle size.

[0030] Example 3, a polypeptide composition was prepared according to the following prescription: Table 4 Prescription of Example 3 composition (100 g)

[0031] The specific preparation process is as follows: Step 1: The polypeptide was dissolved in phosphate buffer with pH 6.8 according to the prescription amount, and a solution with a polypeptide concentration of 10 mg / mL was prepared. The purslane extract, dipotassium glycyrrhizinate, and ceramide NP were added and stirred uniformly. Step 2: The liposome was dissolved in 25 ml of a mixed solvent of ethyl acetate / methanol (3:1, v / v) to prepare a lipid solution with a concentration of 20 mg / mL. The lipid solution was placed in a rotary evaporator and evaporated under reduced pressure at 40°C and -0.08 MPa to form a uniform lipid film.

[0032] Step 3: The polypeptide-containing PBS solution prepared in Step 1 was added, and purified water was added. The lipid film was completely hydrated by stirring in a 40°C water bath for 30 min. The mixture was transferred to an ultrasonic cell disruptor and ultrasonically treated (power 300 W, working 5 s / intermittent 5 s, total time 10 min) under ice bath conditions to form a liposome suspension.

[0033] Step 4: The liposome suspension was extruded through a polycarbonate membrane with a pore size of 100 nm (extrusion pressure 0.8 MPa, cycle number 5 times), and freeze-dried to obtain liposomes with uniform particle size.

[0034] Example 4, polypeptide composition was prepared according to the following prescription: Table 5 Example 4 composition prescription (100 g)

[0035] The specific preparation process is as follows: Step 1: The review peptide is dissolved in phosphate buffer solution with pH 6.8 according to the prescription amount, and a polypeptide solution with a concentration of 10 mg / mL is prepared, and the extract of spilanthes acmella, dipotassium glycyrrhizinate and ceramide NP are added and stirred uniformly; Step 2: The liposome is dissolved in 20 ml of ethyl acetate / methanol mixed solvent (3:1, v / v), and a lipid solution with a concentration of 20 mg / mL is prepared; The lipid solution is placed in a rotary evaporator and evaporated under reduced pressure at 40°C and-0.08 MPa to form a uniform lipid film.

[0036] Step 3: Add the polypeptide-containing PBS solution prepared in step 1, add purified water, and stir in a 40°C water bath for 30 min to completely hydrate the lipid film, and then transfer to an ultrasonic crusher, and ultrasonic treatment (power 300 W, work 5 s / interval 5 s, total time 10 min) under ice bath condition to form a liposome suspension.

[0037] Step 4: The liposome suspension is extruded through a polycarbonate membrane with a pore size of 100 nm (extrusion pressure 0.8 MPa, cycle times 5 times), and freeze-dried to obtain liposomes with uniform particle size.

[0038] Example 5, polypeptide composition was prepared according to the following prescription: Table 6 Example 5 composition prescription (100 g)

[0039] The specific preparation process is as follows: Step 1: The review peptide is dissolved in phosphate buffer solution with pH 6.8 according to the prescription amount, and a polypeptide solution with a concentration of 10 mg / mL is prepared, and the extract of spilanthes acmella, dipotassium glycyrrhizinate and ceramide NP are added and stirred uniformly; Step 2: The liposome is dissolved in 200 ml of ethyl acetate / methanol mixed solvent (3:1, v / v), and a lipid solution with a concentration of 20 mg / mL is prepared; The lipid solution is placed in a rotary evaporator and evaporated under reduced pressure at 40°C and-0.08 MPa to form a uniform lipid film.

[0040] Step 3: Add the polypeptide-containing PBS solution prepared in Step 1, add purified water, stir in a 40°C water bath for 30 min to completely hydrate the lipid film, transfer to an ultrasonic cell disruptor, and ultrasonically treat (power 300 W, work 5 s / intermittent 5 s, total time 10 min) under ice bath conditions to form a liposome suspension.

[0041] Step 4: Extrude the liposome suspension through a polycarbonate membrane extruder with a pore size of 100 nm (extrusion pressure 0.8 MPa, cycle number 5 times), and freeze-dry to obtain liposomes with uniform particle size.

[0042] Comparative Example 1, a polypeptide composition was prepared according to the following prescription: Table 7. Prescription of Comparative Example 1 composition (100 g)

[0043] The specific preparation process is as follows: Step 1: Dissolve the polypeptide according to the prescription amount in a phosphate buffer with a pH of 6.8 to prepare a solution with a polypeptide concentration of 10 mg / mL, and add the purslane extract, dipotassium glycyrrhizinate, and ceramide NP and stir until uniform. Step 2: Dissolve the liposome in 60 ml of a mixed solvent of ethyl acetate / methanol (3:1, v / v) to prepare a lipid solution with a concentration of 20 mg / mL; place the lipid solution in a rotary evaporator and evaporate under reduced pressure at 40°C and -0.08 MPa to form a uniform lipid film.

[0044] Step 3: Add the polypeptide-containing PBS solution prepared in Step 1, add purified water, stir in a 40°C water bath for 30 min to completely hydrate the lipid film, transfer to an ultrasonic cell disruptor, and ultrasonically treat (power 300 W, work 5 s / intermittent 5 s, total time 10 min) under ice bath conditions to form a liposome suspension.

[0045] Step 4: Extrude the liposome suspension through a polycarbonate membrane extruder with a pore size of 100 nm (extrusion pressure 0.8 MPa, cycle number 5 times), and freeze-dry to obtain liposomes with uniform particle size.

[0046] Comparative Example 2, Table 8. Prescription of Comparative Example 2 composition

[0047] The specific preparation process is as follows: Step 1: Dissolve the polypeptide according to the prescription amount in a phosphate buffer with a pH of 6.8 to prepare a solution with a polypeptide concentration of 10 mg / mL, and add the purslane extract, dipotassium glycyrrhizinate, and ceramide NP and stir until uniform. Step 2: The liposome was dissolved in 60 ml of ethyl acetate / methanol mixed solvent (3:1, v / v) to prepare a lipid solution with a concentration of 20 mg / mL; the lipid solution was placed in a rotary evaporator and evaporated under reduced pressure at 40°C and -0.08 MPa to form a uniform lipid film.

[0048] Step 3: The polypeptide-containing PBS solution prepared in Step 1 was added, purified water was added, and the lipid film was completely hydrated by stirring in a 40°C water bath for 30 min. The mixture was transferred to an ultrasonic cell disruptor and ultrasonicated (power 300 W, work 5 s / interval 5 s, total time 10 min) under ice bath conditions to form a liposome suspension.

[0049] Step 4: The liposome suspension was extruded through a polycarbonate membrane with a pore size of 100 nm (extrusion pressure 0.8 MPa, cycle number 5 times), and freeze-dried to obtain liposomes with uniform particle size.

[0050] Example 3, Table 9 Composition prescription of Comparative Example 3

[0051] The specific preparation process is as follows: Step 1: The polypeptide was dissolved in a phosphate buffer with a pH of 6.8 according to the prescription amount to prepare a solution with a polypeptide concentration of 10 mg / mL, and the purslane extract, dipotassium glycyrrhizinate, and ceramide NP were added and stirred uniformly. Step 2: The liposome was dissolved in 60 ml of ethyl acetate / methanol mixed solvent (3:1, v / v) to prepare a lipid solution with a concentration of 20 mg / mL; the lipid solution was placed in a rotary evaporator and evaporated under reduced pressure at 40°C and -0.08 MPa to form a uniform lipid film.

[0052] Step 3: The polypeptide-containing PBS solution prepared in Step 1 was added, purified water was added, and the lipid film was completely hydrated by stirring in a 40°C water bath for 30 min. The mixture was transferred to an ultrasonic cell disruptor and ultrasonicated (power 300 W, work 5 s / interval 5 s, total time 10 min) under ice bath conditions to form a liposome suspension.

[0053] Step 4: The liposome suspension was extruded through a polycarbonate membrane with a pore size of 100 nm (extrusion pressure 0.8 MPa, cycle number 5 times), and freeze-dried to obtain liposomes with uniform particle size.

[0054] Example 4, Table 11 Composition prescription of Comparative Example 4

[0055] The specific preparation process is as follows: Step 1: The rechecked peptide was dissolved in phosphate buffer with pH 6.8 according to the prescription amount, and a solution with a polypeptide concentration of 10 mg / mL was prepared. The purslane extract, glycyrrhizic acid dipotassium, and ceramide NP were added and stirred uniformly. Step 2: The liposome was dissolved in 60 ml of a mixed solvent of ethyl acetate / methanol (3:1, v / v) to prepare a lipid solution with a concentration of 20 mg / mL. The lipid solution was placed in a rotary evaporator and evaporated under reduced pressure at 40°C and -0.08 MPa to form a uniform lipid film.

[0056] Step 3: The polypeptide-containing PBS solution prepared in step 1 was added, and purified water was added. The lipid film was completely hydrated by stirring in a 40°C water bath for 30 min. The mixture was transferred to an ultrasonic cell disruptor and ultrasonically treated (power 300 W, working 5 s / intermittent 5 s, total time 10 min) under ice bath conditions to form a liposome suspension.

[0057] Step 4: The liposome suspension was extruded through a polycarbonate membrane with a pore size of 100 nm (extrusion pressure 0.8 MPa, cycle number 5 times), and freeze-dried to obtain liposomes with uniform particle size.

[0058] Comparative Example 5, Table 12 Formulation of Comparative Example 5

[0059] The specific preparation process is as follows: Step 1: The rechecked peptide was dissolved in phosphate buffer with pH 6.8 according to the prescription amount, and a solution with a polypeptide concentration of 10 mg / mL was prepared. The purslane extract, glycyrrhizic acid dipotassium, and ceramide NP were added and stirred uniformly. Step 2: The hyaluronic acid was added to 60 ml of a mixed solvent of ethyl acetate / methanol (3:1, v / v) to prepare a solution with a concentration of 20 mg / mL. The solution was placed in a rotary evaporator and evaporated under reduced pressure at 40°C and -0.08 MPa to form a transparent film. Step 3: The polypeptide-containing PBS solution prepared in step 1 was added, and purified water was added. The transparent film was completely hydrated by stirring in a 40°C water bath for 30 min. The mixture was transferred to an ultrasonic cell disruptor and ultrasonically treated (power 300 W, working 5 s / intermittent 5 s, total time 10 min) under ice bath conditions to form a suspension. Step 4: The suspension was extruded through a polycarbonate membrane with a pore size of 100 nm (extrusion pressure 0.8 MPa, cycle number 5 times), and freeze-dried to obtain liposomes with uniform particle size.

[0060] Verification Example:

[0061] 1. Stability test, test method: heat resistance test is placed at 45±2℃ for three months, observe the appearance, color and odor; cold resistance test is placed at-18±2℃ for three months, observe the appearance, color and odor of the cream; cold and heat cycle resistance test is placed at 45℃, room temperature and-18℃ for 24h each, cycle 3 times, observe the appearance, color and odor of the cream. The test results are shown in Table 15.

[0062] Table 13 Stability test results

[0063] As can be seen from Table 13, the polypeptide composition examples 1-5 of the present application have excellent stability, which can ensure the unchanged properties under high temperature, low temperature and high-low temperature cycle conditions, wherein the spilanthes acuta extract, dipotassium glycyrrhizinate, ceramide NP and liposome promote each other in stability and have unexpected synergistic effect.

[0064] 2. Itching effect test, the polypeptide composition prepared in the examples is further prepared into an emulsion according to the following formula Table 14 Formula of polypeptide composition emulsion

[0065] Preparation method Step 1: dissolve the complex polypeptide liposome in PBS (pH 6.8) to prepare a solution with a concentration of 5 mg / mL, add glycerol and stir uniformly to make solution A; Step 2: slowly drop squalane and capric acid triglyceride into solution A in a high-speed shearing machine to form a preliminary emulsion; Step 3: transfer the preliminary emulsion to a high-pressure homogenizer, homogenize under high pressure, filter bacteria with a microporous membrane, and fill into a sterile container to obtain a polypeptide composition emulsion.

[0066] Specific experiment: C57BL / 6 mice 220, body weight 20±2g, half male and half female, randomly divided into 11 groups, model control group, positive control group (pifengping ointment), example 1-5 emulsion group, comparative example 1-5 emulsion group.

[0067] The skin on the back of the right hind foot of the mouse was polished with fine sandpaper until the skin was red and bleeding but not bleeding. 0.02% histamine phosphate 0.1 mL was dropped on the polished skin, and the number of mouse itching and duration within 15 min was immediately observed and recorded. The itching indication was that the mouse licked the right hind foot back skin; the itching duration interval of more than 3 seconds was counted as twice itching, and less than 3 seconds was counted as once itching. Immediately after modeling, the drug soap was dipped in water and evenly applied to the skin on the back of the right hind foot of the mouse and gently for a while, and the number of mouse itching (total number) and duration (total duration) within 15 min were observed and recorded, and the results are shown in Table 15.

[0068] Table 15 Anti-itching effect on histamine phosphate-induced itching

[0069] The above results show that when the emulsion is applied to the skin of the itching model mouse, it has a significant anti-itching effect, better than the positive drug (Pidanping ointment) control group, and the anti-itching effect is accurate. It can be seen from Comparative Examples 1-5 that acetyl dipeptide-1 has a good anti-itching effect, and the extract of purslane, dipotassium glycyrrhizinate, ceramide NP, and liposome have a synergistic effect.

[0070] 3. Test of treatment of skin inflammation, material preparation: 40 SD rats were depilated on the back with depilatory cream 1 day before animal modeling, the area was 3 cm x 3 cm, 1 day after depilation, 50L 5% 2,4-dinitrochlorobenzene (DNCB) was applied to the depilation area for the first time; 8 days later, the depilation area was depilated again, and 2 days after the second depilation, 100L 1% DNCB was applied outside the depilation area for the second time. Sensitization with 100L 1% DNCB once a week for 4 weeks. 3 days after the last sensitization, the modeling was completed, and the rat skin surface showed symptoms such as keratinization, patchy erythema, scabbing, epidermal extension, acanthosis, mild spongiotic edema, etc., which indicated that the modeling was successful.

[0071] Experimental process: 30 SD rats with successful modeling were randomly divided into model group (normal saline), positive control group (0.1% hydrocortisone butyrate cream, dose: 1.0 g / kg) and experimental group (prepared according to the prescription of Example 1 and Table 14, dose: 80 g per ear) according to the number random table method, 10 rats in each group, transdermal administration for 5 weeks.

[0072] Efficacy evaluation symptom score: analyze the degree of rat skin mossification, erythema and papules, and grade the severity of symptoms.

[0073] Mossification: 0 points for no mossification, 1 point for a small amount of fine scales, 2 points for obvious fine scales, and 3 points for a large amount of scales.

[0074] Erythema: 0 point for no erythema, 1 point for slightly visible micro-erythema, 2 points for obvious light red erythema, 3 points for a large number of dark red erythema.

[0075] Papule: 0 point for no papule, 1 point for scattered papule, 2 points for papule fusion and dense, 3 points for obvious papule fusion and dense.

[0076] Table 16 Treatment effect score

[0077] Note: The lower the score, the better the effect The above results show that the new polypeptide composition designed by the application can directly kill pathogenic bacteria and reduce and alleviate inflammatory response, and can be used for treating skin inflammation.

[0078] It is explained that the embodiments of the application are only used for illustrating the application, but not limiting the application, so that the simple improvement of the application under the premise of the method of the application is within the protection scope of the application.

Claims

1. A polypeptide composition for anti-allergic, anti-itch and treatment of skin inflammatory related diseases, characterized in that, The polypeptide composition comprises the following ingredients: acetyl dipeptide-1, palmitoyl tripeptide-8, hexapeptide-9, tetrapeptide-3, palmitoyl tripeptide-5, dipeptide-15, acetyl heptapeptide-4 and a complex of excipients.

2. The polypeptide composition of claim 1, wherein, The polypeptide composition comprises the following ingredients in the following weight percentages: 0.2-0.8% acetyl dipeptide-1, 0.02%-0.07% palmitoyl tripeptide-8, 0.02%-0.1% hexapeptide-9, 0.08%-0.15% tetrapeptide-3, 0.05%-0.2% palmitoyl tripeptide-5, 0.05%-0.2% dipeptide-15, 0.02%-0.1% acetyl heptapeptide-4, and the rest is excipients.

3. The polypeptide composition of claim 1, wherein, The polypeptide composition further comprises the following ingredients: purslane extract, dipotassium glycyrrhizinate, ceramide NP, liposomes and purified water.

4. The polypeptide composition of claim 3, wherein, The polypeptide composition further comprises the following ingredients: purslane extract, dipotassium glycyrrhizinate, ceramide NP, liposomes and purified water.

5. The polypeptide composition of claim 3, wherein, The liposomes in the composition are phosphatidylcholine and cholesterol, and the mass ratio of phosphatidylcholine to cholesterol is 3:

1.

6. The polypeptide composition of claim 3, wherein The polypeptide composition is encapsulated by liposomes.

7. A method for preparing the polypeptide composition of claims 1-6 for use in the treatment of skin inflammatory-related diseases, characterized by, The preparation method comprises the following steps: Step 1: dissolve the complex peptides in a phosphate buffer solution with a pH of 6.8 according to the prescription amount, to prepare a polypeptide solution with a concentration of 10 mg / mL, and then add purslane extract, dipotassium glycyrrhizinate and ceramide NP and stir until uniform; Step 2: prepare liposomes by the film dispersion method; Step 3: add the polypeptide solution of step 1 to the liposomes, stir to coat, freeze-dry, and obtain the polypeptide composition.

8. Use of the polypeptide composition of claims 1-6 for the preparation of a medicament or cosmetic product for the treatment of skin problems such as anti-allergy, itching and the like.

9. Use according to claim 8, characterized in that, The polypeptide composition can be prepared into an emulsion for the treatment of skin problems, and the emulsion comprises the polypeptide composition and pharmaceutically acceptable emulsion excipients.

10. Use according to claim 8, characterized in that, The emulsion excipients comprise squalane, glycerol and a pH regulator.

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