Medicine prescription for treating radiodermatitis and application thereof

Abstract

The invention relates to a medicine prescription for treating radiodermatitis and application thereof. The medicine comprises the following components in percentage by weight: 0.01%-2% of acetate of a peptide compound, 2%-5% of a first solvent, 0.05%-1.75% of a bacteriostatic agent, 0.5%-3% of a gel matrix, 0.05%-3% of a metal ion complexing agent, a pH regulator for regulating the pH value to 3-7, and a second solvent supplemented to 100%. The prescription of the medicine for treating radiodermatitis is especially suitable for symptomatic treatment of chronic pruritus such as atopic dermatitis, and the local action mechanism of the medicine gives consideration to both curative effect and safety. The medicine can be directly administered to an affected part, so that the uncertainty of in-vivo circulation is reduced; the use by patients is convenient and the compliance is improved.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to a drug prescription for treating radiation dermatitis and its application. Background Technology

[0002] Radiation-associated pruritus (RAP) refers to a complication caused by localized radiation exposure (such as X-rays and gamma rays), characterized primarily by itching. It is commonly seen in patients receiving radiation therapy for breast cancer, head and neck tumors, and skin cancer. Its occurrence is closely related to radiation-induced damage to the skin barrier, release of inflammatory mediators, and sensitization of nerve endings. Atopic dermatitis pruritus, on the other hand, is an immune-mediated disease characterized by chronic, recurrent skin inflammation. Itching is its core and most distressing symptom, with approximately 90% of patients experiencing persistent itching. Although these two diseases have different causes, both present with intense and persistent localized itching. Patients are prone to unconsciously scratching, leading to a vicious cycle of "itching-scratching-skin lesions," resulting in skin damage, crusting, lichenification, or secondary infections, severely impacting quality of life and treatment of the primary disease. Currently, there are no specific and safe treatments for either of these types of itching in clinical practice.

[0003] Therefore, developing a therapeutic drug that can effectively relieve these two types of itching, repair the skin barrier, and is suitable for topical application is of great clinical significance and application value.

[0004] The occurrence of atopic dermatitis and radiation therapy-related pruritus is closely related to impaired skin barrier function, active inflammatory response, and abnormal pruritus signals. Studies have shown that key receptors and nerve endings related to pruritus are mainly distributed in the stratum corneum and superficial epidermal nerve fibers, which determines the direct and significant advantage of topical preparations in relieving pruritus. Clinically, these patients often have dry skin, cracked skin, and even micro-wounds. If topical preparations contain insoluble impurities or irritating ingredients, they can easily aggravate skin damage and reduce compliance. At the same time, although traditional oral or injectable antipruritic drugs can play a certain role, their effectiveness is often limited due to significant systemic adverse reactions and the difficulty in concentrating their effects on the local skin.

[0005] Therefore, there is an urgent need for a novel topical formulation that can directly target the itchy spots on the skin surface, has few impurities, good spreadability, moderate transdermal permeability, and minimal irritation to skin with damaged barriers, so as to balance efficacy and safety and meet the clinical needs of patients with atopic dermatitis and radiation-induced skin damage-related itching. Summary of the Invention

[0006] To address the aforementioned technical problems, this invention provides a pharmaceutical formulation for treating radiation dermatitis and its application. By weight percentage, the gel of this invention comprises the following components: 0.01%-2% acetate of peptide compounds, 2-5% of a first solvent, 0.05%-1.75% of an antibacterial agent, 0.5%-3% of a gel matrix, 0.05%-3% of a metal ion chelating agent, a pH adjuster to adjust the pH to 3-7, and a second solvent to bring the total to 100%. This pharmaceutical formulation for treating radiation dermatitis is particularly suitable for the symptomatic treatment of chronic itching such as atopic dermatitis, and its local mechanism of action balances efficacy and safety. In its formulation design, this invention minimizes the use of transdermal excipients, such as white petrolatum, stearic acid, and Tween 80, aiming to direct the drug at Kaapa receptors to achieve epidermal antipruritic effects.

[0007] The acetate of the peptide compound used in this invention is a selective κ-opioid receptor agonist, capable of activating κ-opioid receptors in the stratum corneum and superficial epidermal nerve endings, thereby inhibiting the transmission of pruritus signals and significantly alleviating patients' itching symptoms. Studies have shown that κ-opioid receptors are a promising new therapeutic target for regulating the pruritus pathway in atopic dermatitis and relieving pain symptoms in radiotherapy-associated dermatitis. This invention prepares the acetate of the peptide compound into a topical gel formulation, which can be directly applied to the affected skin. This achieves highly effective local itch relief, reduces the risk of systemic adverse reactions, and improves the limitations of injectable formulations due to poor compliance. It is particularly suitable for the treatment of atopic dermatitis and radiotherapy-related pruritus.

[0008] This invention is achieved through the following technical solution:

[0009] The first objective of this invention is to provide a pharmaceutical formulation for treating radiation dermatitis, comprising, by weight percentage: 0.01%-2% acetate of a peptide compound, 2-5% of a first solvent, 0.05%-1.75% of an antibacterial agent, 0.5%-3% of a gel matrix, 0.05%-3% of a metal ion chelating agent, a pH adjuster to adjust the pH value to 3-7, and the remainder being a second solvent; the structural formula of the peptide compound is as follows:

[0010]

[0011] The structural formula of the acetate of the peptide compound is as follows:

[0012]

[0013] In one embodiment of the present invention, the first solvent is selected from one or more of alcohols, amines, dimethyl sulfoxide, diethylene glycol monoethyl ether (Transcutol P), fatty acid esters, N-methyl-2-pyrrolidone, and tetrahydrofuran polyethylene glycol ether;

[0014] The alcohol is one or more of propylene glycol, polyethylene glycol, ethanol, isopropanol, 1,3-butanediol, hexanediol, benzyl alcohol, and glycerol; the amine is one or more of dimethylacetamide, ethanolamine, and triethanolamine; the fatty acid ester is triglyceride and / or isopropyl myristate; and the polyethylene glycol is PEG 200, PEG 300, or PEG 400.

[0015] In one embodiment of the present invention, the antibacterial agent is selected from one or more of methylparaben, propylparaben, benzyl alcohol, phenoxyethanol, sorbic acid, benzoic acid, chlorocresol, and chlorobutanol.

[0016] In one embodiment of the present invention, the gel matrix is ​​selected from carbomer.

[0017] In one embodiment of the present invention, the metal ion complexing agent is selected from disodium edetate.

[0018] In one embodiment of the present invention, the pH adjuster is selected from one or more of hydrochloric acid, acetic acid, sodium hydroxide, lactic acid, phosphate buffer, and acetate buffer.

[0019] In one embodiment of the present invention, the second solvent is selected from water and / or propylene glycol.

[0020] A second objective of this invention is to provide a method for preparing the drug prescription for treating radiation dermatitis, comprising the following steps:

[0021] (1) Disperse the gel matrix in water, add a metal ion complexing agent and stir to obtain a matrix dispersion;

[0022] (2) Dissolve the antibacterial agent in the first solvent to obtain an antibacterial solution;

[0023] (3) The obtained matrix dispersion is mixed with the antibacterial solution, and a gel matrix containing antibacterial agent is obtained by stirring and soaking.

[0024] (4) Stir the aqueous solution of the acetate of the peptide compound with the obtained gel matrix containing the antibacterial agent, homogenize, add pH adjuster and stir to homogenize, and obtain a gel that relieves or treats skin itching.

[0025] A third objective of this invention is to provide the application of the aforementioned drug formulation for treating radiation dermatitis in the preparation of a drug for treating atopic dermatitis with itching.

[0026] A fourth objective of this invention is to provide the use of the aforementioned pharmaceutical formulation for treating radiation dermatitis in the preparation of a medicament for relieving or preventing skin itching and / or atopic dermatitis caused by radiotherapy.

[0027] This invention selects an aqueous matrix with low irritation for drug formulation preparation. Simultaneously, the acetates of peptide compounds exhibit good solubility (≥100 mg / mL), classifying them as highly soluble. Using an aqueous matrix facilitates the development of high-dose formulations and enhances drug efficacy.

[0028] The technical solution of the present invention has the following advantages compared with the prior art:

[0029] (1) This invention provides a drug prescription for treating radiation dermatitis and its application. The gel of this invention is applied directly to the patient to release the drug, which binds to κ-opioid receptors on the skin surface, stimulates these receptors, and inhibits the peripheral transmission of itch signals, thereby achieving the purpose of itch suppression.

[0030] (2) The present invention uses a gel matrix to disperse the drug on the gel matrix and release it slowly through contact with the affected area to achieve long-term inhibition.

[0031] (3) The drug prescription of the present invention can be administered directly to the affected area, reducing the uncertainty of circulation in the body; it is convenient for patients to use and increases compliance. Detailed Implementation

[0032] The present invention will be further described below with reference to specific embodiments, so that those skilled in the art can better understand and implement the present invention, but the embodiments are not intended to limit the present invention.

[0033] This invention provides a pharmaceutical prescription for treating radiation dermatitis, used to relieve or treat skin itching, comprising the following components:

[0034]

[0035] The preparation process is as follows:

[0036] 1) Preparation of the substrate

[0037] a. Add 76% water to the aqueous phase tank, turn on the stirrer at a speed of 30-50 Hz, and slowly add the gel matrix (for no less than 30 minutes) while trying to avoid agglomeration. After the addition is complete, add the remaining water, keep stirring, add disodium edetate, and at the same time prepare the antibacterial solution.

[0038] b. Preparation of antibacterial solution: Add the prescribed amount of propylene glycol to a stainless steel container, add phenoxyethanol, and stir using a digital display constant speed stirrer at a speed of 200-400 rpm.

[0039] Add the prescribed amount of methylparaben and 1% of the total amount of water, stir until completely dissolved, and obtain a clear solution.

[0040] c. Mixing and swelling: Add the antibacterial solution to the matrix dispersion phase in step a above, and rinse the container prepared with the antibacterial solution in step b with 2% of the total amount of water several times before adding it together; stop the machine and scrape the material during the stirring process, continue stirring for more than 1 hour, stop stirring, and soak until fully swollen; after swelling, continue stirring for more than 30 minutes, and there should be no unswollen lumps visible.

[0041] 2) Preparation of drug dispersion

[0042] Add an appropriate amount of aqueous solution to the container, add the prescribed amount of peptide compound acetate, stir for 30 minutes, and set aside.

[0043] 3) Gel preparation

[0044] a. The gel matrix is ​​transferred to a vacuum emulsifying mixer, and the aqueous phase tank is rinsed several times with 4% of the total amount of water prepared, and then transferred to the vacuum emulsifying mixer.

[0045] b. Seal the vacuum emulsifying mixer, evacuate to below -0.06MPa, start stirring, speed 10-30rpm, maintain vacuum stirring for more than 10 minutes, and there should be no obvious bubbles visible.

[0046] c. Bring the vacuum emulsifying mixer to atmospheric pressure, start homogenization at 1000-4000 rpm, and slowly add the prepared drug dispersion (avoiding the agitator during addition); rinse the preparation container several times with 2% of the total amount of water, and add it to the vacuum emulsifying mixer; evacuate to below -0.06 MPa, start stirring (10-30 rpm) and homogenizing (400-600 rpm), and homogenize for 10 minutes, then release the pressure to atmospheric pressure.

[0047] d. Adjust the stirring speed to 20-40 rpm and keep the homogenization speed at 400-600 rpm. Slowly add the pH adjuster through the feeding port. After all the pH adjuster has been added, evacuate to below -0.06 MPa and continue stirring and homogenizing for 15 minutes. Then stop evacuation, stirring and homogenization. Take pH samples at five points: front, back, left, right and center of the preparation tank. The required pH value is 3-7.

[0048] Unless otherwise specified, the experimental methods used in the following examples are conventional methods, and the materials and reagents used are commercially available.

[0049] Example 1

[0050] This embodiment provides a drug prescription for treating radiation dermatitis, as follows:

[0051] By weight percentage, the components are:

[0052]

[0053]

[0054] The preparation method of the drug prescription for treating radiation dermatitis is as follows:

[0055] (1) Preparation of the substrate

[0056] 1) Prepare 76% water in the aqueous phase tank, turn on the stirrer at 50 Hz, and slowly add carbomer homopolymer C type 980NF (for no less than 30 min) to avoid agglomeration as much as possible; after the addition is complete, add the remaining water, keep stirring, add disodium edetate to obtain the matrix dispersion phase.

[0057] 2) Preparation of antibacterial solution: Add the prescribed amount of propylene glycol to a stainless steel container, add phenoxyethanol, and stir using a digital display constant speed stirrer at a speed of 400 rpm;

[0058] Add the prescribed amount of methylparaben and 1% water (total amount), and stir until completely dissolved to obtain an antibacterial solution.

[0059] 3) Mixing and swelling: Add the antibacterial solution obtained in step 2) to the matrix dispersion phase in step 1), and rinse the container prepared with the antibacterial solution in step 2) with 2% water in total amount several times before adding it together; stop the stirring and scrape the material during the stirring process, continue stirring for 1 hour, stop stirring and soak until completely swollen; after swelling, continue stirring for 30 minutes, and visually inspect for any unswollen clumps to obtain a gel matrix containing antibacterial agent.

[0060] (2) Preparation of drug dispersion

[0061] Add an appropriate amount of water to the container, add the prescribed amount of acetate of the peptide compound, stir for 30 minutes to obtain a drug dispersion, and set aside for later use.

[0062] (3) Gel preparation

[0063] a. Transfer the gel matrix containing the antibacterial agent to a vacuum emulsifying mixer, rinse the aqueous phase tank several times with 4% of the total amount of water, and then transfer it to the vacuum emulsifying mixer.

[0064] b. Seal the vacuum emulsifying mixer, evacuate to -0.06MPa, start stirring, speed 30rpm, maintain vacuum stirring for 10min, and there should be no obvious bubbles visible.

[0065] c. Bring the vacuum emulsifying mixer to atmospheric pressure, start homogenization at 3000 rpm, and slowly add the prepared drug dispersion (avoiding the agitator when adding); rinse the preparation container several times with 2% of the total amount of water, and add it to the vacuum emulsifying mixer; evacuate to -0.06 MPa, start stirring (30 rpm) and homogenizing (500 rpm), stir and homogenize for 10 minutes, and then release the pressure to atmospheric pressure.

[0066] d. Adjust the stirring speed to 30 rpm and keep the homogenization speed at 500 rpm constant. Slowly add the pH adjuster through the feeding port. After all the pH adjuster has been added, evacuate to -0.06 MPa and continue stirring and homogenizing for 15 minutes. Then stop evacuation, stirring and homogenization. Take pH samples at five points (front, back, left, right and center) of the preparation tank and measure the pH value. The required pH value is 4.5. The resulting gel that relieves or treats skin itching is the prescription for treating radiation dermatitis.

[0067] Example 2

[0068] This embodiment provides a drug prescription for treating radiation dermatitis, as follows:

[0069] By weight percentage, the components are:

[0070] Components Weight percentage (%) Acetates of peptide compounds 1.00 Propylene glycol 3.50 Methylparaben 0.15 Phenoxyethanol 0.75 Carbomer homopolymer C type 980NF 2 Sodium edetate 3 Acetic acid buffer salt Adjust the pH to 4.5. water Increase to 100.0

[0071] The preparation method of the drug prescription for treating radiation dermatitis is similar to that in Example 1.

[0072] Example 3

[0073] This embodiment provides a drug prescription for treating radiation dermatitis, as follows:

[0074] By weight percentage, the components are:

[0075] Components Weight percentage (%) Acetates of peptide compounds 2.00 Propylene glycol 5.00 Methylparaben 0.25 Phenoxyethanol 1.5 Carbomer homopolymer C type 980NF 3 Sodium edetate 1 Acetic acid buffer salt Adjust the pH to 4.5. water Increase to 100.0

[0076] The preparation method of the drug prescription for treating radiation dermatitis is similar to that in Example 1.

[0077] Example 4

[0078] This embodiment provides a drug prescription for treating radiation dermatitis, specifically as follows: The components, by weight percentage, are:

[0079] Components Weight percentage (%) Acetates of peptide compounds 0.01 Propylene glycol 3.50 Methylparaben 0.15 Phenoxyethanol 0.75 Carbomer homopolymer C type 980NF 2 Sodium edetate 3 Acetic acid buffer salt Adjust the pH to 4.5. water Increase to 100.0

[0080] The preparation method of the drug prescription for treating radiation dermatitis is similar to that in Example 1.

[0081] Example 5

[0082] This embodiment provides a drug prescription for treating radiation dermatitis, specifically as follows: The components, by weight percentage, are:

[0083] Components Weight percentage (%) Acetates of peptide compounds 1.00 Propylene glycol 2 Methylparaben 0.05 Phenoxyethanol 0.05 Carbomer homopolymer C type 980NF 0.50 Sodium edetate 0.05 Acetic acid buffer salt Adjust the pH to 4.5. water Increase to 100.0

[0084] The preparation method of the drug prescription for treating radiation dermatitis is similar to that in Example 1.

[0085] Example 6

[0086] This embodiment provides a drug prescription for treating radiation dermatitis, specifically as follows: The components, by weight percentage, are:

[0087]

[0088]

[0089] The preparation method of the drug prescription for treating radiation dermatitis is similar to that in Example 1.

[0090] Example 7

[0091] This embodiment provides a drug prescription for treating radiation dermatitis, specifically as follows: The components, by weight percentage, are:

[0092] Components Weight percentage (%) Acetates of peptide compounds 0.01 Propylene glycol 5.00 Methylparaben 0.25 Phenoxyethanol 1.5 Carbomer homopolymer C type 980NF 3 Sodium edetate 1 Acetic acid buffer salt Adjust the pH to 4.5. water Increase to 100.0

[0093] The preparation method of the drug prescription for treating radiation dermatitis is similar to that in Example 1.

[0094] Example 8

[0095] This embodiment provides a drug prescription for treating radiation dermatitis, specifically as follows: The components, by weight percentage, are:

[0096] Components Weight percentage (%) Acetates of peptide compounds 1.00 Propylene glycol 5.00 Methylparaben 0.25 Phenoxyethanol 1.5 Carbomer homopolymer C type 980NF 3 Sodium edetate 1 Acetic acid buffer salt Adjust the pH to 4.5. water Increase to 100.0

[0097] The preparation method of the drug prescription for treating radiation dermatitis is similar to that in Example 1.

[0098] Example 9

[0099] This embodiment provides a drug prescription for treating radiation dermatitis, specifically as follows: The components, by weight percentage, are:

[0100] Components Weight percentage (%) Acetates of peptide compounds 2.00 Propylene glycol 3.50 Methylparaben 0.15 Phenoxyethanol 0.75 Carbomer homopolymer C type 980NF 2 Sodium edetate 3 Acetic acid buffer salt Adjust the pH to 4.5. water Increase to 100.0

[0101] The preparation method of the drug prescription for treating radiation dermatitis is similar to that in Example 1.

[0102] Example 10

[0103] This embodiment provides a drug prescription for treating radiation dermatitis, specifically as follows: The components, by weight percentage, are:

[0104] Components Weight percentage (%) Acetates of peptide compounds 0.01 Propylene glycol 4 Methylparaben 0.10 Phenoxyethanol 0.25 Carbomer homopolymer C type 980NF 1.10 Sodium edetate 0.10 Acetic acid buffer salt Adjust the pH to 4.5. water Increase to 100.0

[0105] The preparation method of the drug prescription for treating radiation dermatitis is similar to that in Example 1.

[0106] Example 11

[0107] This embodiment provides a drug prescription for treating radiation dermatitis, specifically as follows: The components, by weight percentage, are:

[0108]

[0109]

[0110] The preparation method of the drug prescription for treating radiation dermatitis is similar to that in Example 1.

[0111] Example 12

[0112] This embodiment provides a drug prescription for treating radiation dermatitis, specifically as follows: The components, by weight percentage, are:

[0113] Components Weight percentage (%) Acetates of peptide compounds 0.40 Propylene glycol 4 Methylparaben 0.10 Phenoxyethanol 0.25 Carbomer homopolymer C type 980NF 1.10 Sodium edetate 0.10 Acetic acid buffer salt Adjust the pH to 4.5. water Increase to 100.0

[0114] The preparation method of the drug prescription for treating radiation dermatitis is similar to that in Example 1.

[0115] Example 13

[0116] This embodiment provides a drug prescription for treating radiation dermatitis, specifically as follows: The components, by weight percentage, are:

[0117] Components Weight percentage (%) Acetates of peptide compounds 0.60 Propylene glycol 4 Methylparaben 0.10 Phenoxyethanol 0.25 Carbomer homopolymer C type 980NF 1.10 Sodium edetate 0.10 Acetic acid buffer salt Adjust the pH to 4.5. water Increase to 100.0

[0118] The preparation method of the drug prescription for treating radiation dermatitis is similar to that in Example 1.

[0119] Example 14

[0120] This embodiment provides a drug prescription for treating radiation dermatitis, specifically as follows: The components, by weight percentage, are:

[0121] Components Weight percentage (%) Acetates of peptide compounds 0.80 Propylene glycol 4 Methylparaben 0.10 Phenoxyethanol 0.25 Carbomer homopolymer C type 980NF 1.10 Sodium edetate 0.10 Acetic acid buffer salt Adjust the pH to 4.5. water Increase to 100.0

[0122] The preparation method of the gel for the drug prescription for treating radiation dermatitis is similar to that in Example 1.

[0123] Example 15

[0124] This embodiment provides a drug prescription for treating radiation dermatitis, specifically as follows: The components, by weight percentage, are:

[0125] Components Weight percentage (%) Acetates of peptide compounds 1.00 Propylene glycol 4 Methylparaben 0.10 Phenoxyethanol 0.25 Carbomer homopolymer C type 980NF 1.10 Sodium edetate 0.10 Acetic acid buffer salt Adjust the pH to 4.5. water Increase to 100.0

[0126] The preparation method of the drug prescription for treating radiation dermatitis is similar to that in Example 1.

[0127] Example 16

[0128] This embodiment provides a drug prescription for treating radiation dermatitis, specifically as follows: The components, by weight percentage, are:

[0129]

[0130]

[0131] The preparation method of the drug prescription for treating radiation dermatitis is similar to that in Example 1.

[0132] Example 17

[0133] This embodiment provides a drug prescription for treating radiation dermatitis, specifically as follows: The components, by weight percentage, are:

[0134] Components Weight percentage (%) Acetates of peptide compounds 1.40 Propylene glycol 4 Methylparaben 0.10 Phenoxyethanol 0.25 Carbomer homopolymer C type 980NF 1.10 Sodium edetate 0.10 Acetic acid buffer salt Adjust the pH to 4.5. water Increase to 100.0

[0135] The preparation method of the drug prescription for treating radiation dermatitis is similar to that in Example 1.

[0136] Example 18

[0137] This embodiment provides a drug prescription for treating radiation dermatitis, specifically as follows: The components, by weight percentage, are:

[0138]

[0139]

[0140] The preparation method of the drug prescription for treating radiation dermatitis is similar to that in Example 1.

[0141] Example 19

[0142] This embodiment provides a drug prescription for treating radiation dermatitis, specifically as follows: The components, by weight percentage, are:

[0143] Components Weight percentage (%) Acetates of peptide compounds 1.80 Propylene glycol 4 Methylparaben 0.10 Phenoxyethanol 0.25 Carbomer homopolymer C type 980NF 1.10 Sodium edetate 0.10 Acetic acid buffer salt The pH value is 4.5. water Increase to 100.0

[0144] The preparation method of the drug prescription for treating radiation dermatitis is similar to that in Example 1.

[0145] Example 20

[0146] This embodiment provides a drug prescription for treating radiation dermatitis, specifically as follows: The components, by weight percentage, are:

[0147] Components Weight percentage (%) Acetates of peptide compounds 2.00 Propylene glycol 4 Methylparaben 0.10 Phenoxyethanol 0.25 Carbomer homopolymer C type 980NF 1.10 Sodium edetate 0.10 Acetic acid buffer salt The pH value is 4.5. water Increase to 100.0

[0148] The preparation method of the drug prescription for treating radiation dermatitis is similar to that in Example 1.

[0149] Example 21

[0150] This embodiment provides a drug prescription for treating radiation dermatitis, specifically as follows: The components, by weight percentage, are:

[0151] Components Weight percentage (%) Acetates of peptide compounds 0.60％ Propylene glycol 4％ Methylparaben 0.10％ Phenoxyethanol 0.25％ Carbomer homopolymer C type 980NF 1.10％ Sodium edetate 0.10％ Acetic acid buffer salt The pH value is 3.0. water Increase to 100.0

[0152] The preparation method of the drug prescription for treating radiation dermatitis is similar to that in Example 1.

[0153] Example 21

[0154] This embodiment provides a drug prescription for treating radiation dermatitis, as follows:

[0155] By weight percentage, the components are:

[0156] Components Weight percentage (%) Acetates of peptide compounds 0.60％ Propylene glycol 4％ Methylparaben 0.10％ Phenoxyethanol 0.25％ Carbomer homopolymer C type 980NF 1.10％ Sodium edetate 0.10％ acetate buffer The pH value is 7.0. water Increase to 100.0

[0157] The preparation method of the drug prescription for treating radiation dermatitis is similar to that in Example 1.

[0158] Comparative Example 1

[0159] This comparative example provides a gel composition and preparation method, which is similar to Example 13, except that the amount of propylene glycol added is 1%, and the rest is the same as in Example 13.

[0160] Comparative Example 2

[0161] This comparative example provides a gel composition and preparation method, which is similar to Example 13, except that the amount of propylene glycol added is 6%, and the rest is the same as in Example 13.

[0162] Comparative Example 3

[0163] This comparative example provides a gel composition and preparation method, which is similar to Example 13, except that the amount of methylparaben added is 0.01% and the amount of phenoxyethanol added is 0.01%, while the rest is the same as in Example 13.

[0164] Comparative Example 4

[0165] This comparative example provides a gel composition and preparation method, which is similar to Example 13, except that the amount of methylparaben added is 0.50% and the amount of phenoxyethanol added is 3%, while the rest is the same as in Example 13.

[0166] Comparative Example 5

[0167] This comparative example provides a gel composition and preparation method, which is similar to Example 13, except that the amount of carbomer homopolymer C-type 980NF added is 0.1%, and the rest is the same as in Example 13.

[0168] Comparative Example 6

[0169] This comparative example provides a gel composition and preparation method, which is similar to Example 13, except that the amount of carbomer homopolymer C-type 980NF added is 4%, and the rest is the same as in Example 13.

[0170] Comparative Example 7

[0171] This comparative example provides a gel composition and preparation method, which is similar to Example 13, except that the amount of disodium edetate added is 0.01%, and the rest is the same as in Example 13.

[0172] Comparative Example 8

[0173] This comparative example provides a gel composition and preparation method, which is similar to Example 13, except that the amount of disodium edetate added is 4%, and the rest is the same as in Example 13.

[0174] Comparative Example 9

[0175] This comparative example provides a gel composition and preparation method, which is similar to Example 13, except that: the pH value is adjusted to 2 using acetate buffer, and the rest is the same as Example 13.

[0176] Comparative Example 10

[0177] This comparative example provides a gel composition and preparation method, which is similar to Example 13, except that: the pH value is adjusted to 8 using acetate buffer, and the rest is the same as Example 13.

[0178] Comparative Example 11

[0179] This comparative example provides a peptide compound acetate cream and its preparation method, as detailed below:

[0180] The acetate cream components of peptide compounds, by weight percentage, are:

[0181] composition content(%) Acetates of peptide compounds 1 monostearate 2 α-Cyclodextrin 2 stearic acid 5 Vaseline 5 Twain 80 15 water 67 benzyl alcohol 3

[0182] Preparation method of peptide acetate cream: Glyceryl monostearate, α-cyclodextrin, stearic acid, and white petrolatum were heated to 72°C and melted, then stirred until homogeneous to obtain system 1; Tween 80, water, and benzyl alcohol were heated to 75°C and stirred until homogeneous to obtain system 2; system 2 was added to system 1 at 72°C, and stirring was started at 300 rpm for 40 min; then the peptide acetate was added, and homogenization was started at 2000 rpm for 15 min; the mixture was then transferred to a cold water bath and cooled to below 25°C before being dispensed.

[0183] Comparative Example 12

[0184] This comparative example provides a peptide compound acetate cream and its preparation method, as detailed below:

[0185] The acetate cream components of peptide compounds, by weight percentage, are:

[0186] composition content(%) Acetates of peptide compounds 2 monostearate 2 α-Cyclodextrin 2 stearic acid 5 Vaseline 5 Twain 80 15 water 66 benzyl alcohol 3

[0187] The preparation method of the acetate cream of peptide compounds is similar to that of Comparative Example 11.

[0188] Test example:

[0189] (1) The appearance of the gels obtained in the above examples and comparative examples, as well as whether they formed within 24 hours, whether they precipitated, their skin irritation, and their spreadability were tested. The results are shown in Table 1 below:

[0190] Table 1

[0191] name Appearance Is it formed? Whether precipitation occurs Skin irritation Coating properties Example 1 Uniform lubrication forming No precipitation none good Example 2 Uniform lubrication forming No precipitation none good Example 3 Uniform lubrication forming No precipitation none good Example 4 Uniform lubrication forming No precipitation none good Example 5 Uniform lubrication forming No precipitation none good Example 6 Uniform lubrication forming No precipitation none good Example 7 Uniform lubrication forming No precipitation none good Example 8 Uniform lubrication forming No precipitation none good Example 9 Uniform lubrication forming No precipitation none good Example 10 Uniform lubrication forming No precipitation none good Example 11 Uniform lubrication forming No precipitation none good Example 12 Uniform lubrication forming No precipitation none good Example 13 Uniform lubrication forming No precipitation none good Example 14 Uniform lubrication forming No precipitation none good Example 15 Uniform lubrication forming No precipitation none good Example 16 Uniform lubrication forming No precipitation none good Example 17 Uniform lubrication forming No precipitation none good Example 18 Uniform lubrication forming No precipitation none good Example 19 Uniform lubrication forming No precipitation none good Example 20 Uniform lubrication forming No precipitation none good Comparative Example 1 Uniform lubrication forming There is precipitation none Difference Comparative Example 2 Uniform lubrication forming No precipitation have good Comparative Example 3 White fungal spots forming No precipitation none good Comparative Example 4 Poor appearance forming There is precipitation none Difference Comparative Example 5 Uniform lubrication Unformed No precipitation none Difference Comparative Example 6 Poor appearance forming No precipitation none Difference Comparative Example 7 Poor appearance forming No precipitation none Difference Comparative Example 8 Poor appearance forming No precipitation none Difference Comparative Example 9 Uniform lubrication forming No precipitation have good Comparative Example 10 Uniform lubrication forming No precipitation none Difference Comparative Example 11 Uniform lubrication forming No precipitation have good Comparative Example 12 Uniform lubrication forming Precipitation have good

[0192] As can be seen from Table 1, the gel of the present invention for relieving or treating skin itching has a uniform and smooth appearance, can be formed, does not precipitate, does not irritate the skin, has good coating performance, and its overall advantages are superior to those of the comparative example.

[0193] (2) High-performance liquid chromatography (HPLC) was used to detect impurities (acetate salts of non-peptide compounds) in the gels obtained in Examples 13, 15, 20, and Comparative Examples 7-12. 0.1% (v / v) phosphoric acid solution was used as mobile phase A, and acetonitrile was used as mobile phase B for elution. The detection wavelength was 210 nm, and the flow rate was 1.0 mL per minute. The results are shown in Table 2.

[0194] Table 2

[0195] name Total impurities (related substances, n=6) Example 13 0.1±0.02 Example 15 0.1±0.02 Example 20 0.3±0.02 Example 21 0.15±0.02 Example 22 0.23±0.02 Comparative Example 7 0.2±0.03 Comparative Example 8 0.9±0.02 Comparative Example 9 0.5±0.01 Comparative Example 10 3％±0.07 Comparative Example 11 1.25±0.03 Comparative Example 12 1.26±0.02

[0196] As can be seen from Table 2, the impurity content of the gel obtained in the embodiments of the present invention for relieving or treating skin itching is significantly lower than that of the comparative examples. Examples 15, 20, 11, and 12 show that the impurity level increases significantly when formulated as a cream; Examples 13, 21, 22, 9, and 10 show that the impurity level is even lower at pH 3.0-7.0.

[0197] (3) Animal experiments: radiation dermatitis

[0198] Forty-eight SPF-grade BALB / c nude mice were randomly divided into four groups according to weight and sex: a blank control group, a model control group, and treatment groups (Examples 10, 15, 20, and Comparative Example 12), with eight animals in each group. Mice were anesthetized before irradiation, and then irradiated with gamma rays to the skin from the left rump to the foot of each mouse, with a total dose of 60 Gy, 20 Gy / day for three consecutive days. The non-irradiated areas were protected with lead sheeting. Starting on the 9th day after the last modeling, the medication was applied topically at a dose of 0.2 g / mouse, once daily for seven consecutive days. The blank control group and the model control group received the same amount of blank excipient via skin application.

[0199] The composition of the blank excipient, by weight percentage, is as follows:

[0200] Components Weight percentage (%) Acetates of peptide compounds 0 Propylene glycol 4 Methylparaben 0.10 Phenoxyethanol 0.25 Carbomer homopolymer C type 980NF 1.10 Sodium edetate 0.10 Acetic acid buffer salt Adjust the pH to 4.5. water Increase to 100.0

[0201] After the last administration, skin lesions in mice were visually assessed. The assessment used four indicators: erythema, edema, erosion, and moist desquamation. Each indicator was graded from 0 to 3 (0 for no abnormality, 3 for the most severe). The total score for skin lesions was the sum of the scores for the four indicators, ranging from 0 to 12, and could be used to objectively characterize the severity of the skin lesions. The results are shown in Table 3 below:

[0202] Table 3. Effects of the examples on the skin appearance score of mice with radiation dermatitis ( n=8)

[0203] Group Dosage (g / animal) Appearance rating (P) Blank control group 0.2 0.00±0.00 Model control group 0.2 <![CDATA[9.75±0.71 ++ ]]> Example 10 0.2 8.25±1.04** Example 15 0.2 7.88±0.64** Example 20 0.2 7.50±0.93** Comparative Example 12 0.2 9.38±0.52

[0204] Note: Compared with the blank control group ++ P≤0.01; Comparison between model and control groups * P≤0.05, ** P≤0.01.

[0205] As can be seen, compared with the blank control group, the skin appearance score of mice in the model control group was significantly increased (P≤0.01); compared with the model control group, the skin appearance scores of mice in the treatment groups of Example 10, Example 15 and Example 20 were significantly decreased (P≤0.05), and there was no statistically significant difference in the skin appearance score of mice in Comparative Example 12.

[0206] In addition, the number of times mice scratched their hind feet within 30 minutes before and after the last administration was observed in a quiet cage. Evaluation criteria: The number of times mice scratched the itchy areas with their hind paws was used as an indicator of pruritus behavior; scratching of other areas such as the ears was ignored.

[0207] Table 4. Effects of the examples on skin itching in mice with radiation dermatitis ( n=8)

[0208]

[0209] Note: Compared with the blank control group ++ P≤0.01; Comparison between model and control groups * P≤0.05, ** P≤0.01.

[0210] As can be seen, compared with the blank control group, the number of skin itching episodes in the model control group mice was significantly increased (P≤0.01); compared with the model control group, the number of skin itching episodes in the treatment groups of Examples 10, 15 and 20 was significantly reduced (P≤0.05 or P≤0.01).

[0211] (4) Animal experiments: atopic dermatitis

[0212] Forty-eight SPF-grade 8-week-old female C57BL / 6 mice were randomly divided into four groups (n=8 per group) according to weight and sex: a blank control group, a model control group, and treatment groups (Examples 10, 15, 20, and Comparative Example 12). Before modeling, mice were anesthetized, and MC903 was applied topically to the skin behind the ear to induce atopic dermatitis. This was repeated once daily for 14 consecutive days. Treatment began on day 8 after modeling. One hour after MC903 treatment, the same area was treated with 0.2 g of MC903 once daily for 7 consecutive days. The blank control group and the model control group received an equal amount of blank excipient via skin application. During the experiment, skin damage and itching were assessed according to a predetermined scoring system, including erythema, edema, erosion, and moist desquamation, each scored from 0 to 3 points. The sum of the four scores was the total skin damage score (0-12 points), used to objectively characterize the severity of skin lesions. The number of scratch marks was counted within 30 minutes after the last administration.

[0213] Table 5. Effects of the examples on skin appearance scores in mice with atopic dermatitis ( n=8)

[0214]

[0215]

[0216] Note: Compared with the blank control group ++ P≤0.01; Comparison between model and control groups * P≤0.05, **P≤0.01.

[0217] Table 6. Effects of the examples on skin itching in mice after radiation ( n=8)

[0218] Group Dosage (g / animal) Number of times itching Blank control group 0.2 0.88±0.64 Model control group 0.2 <![CDATA[27.50±8.30 ++ ]]> Example 10 0.2 <![CDATA[20.00±4.41 * ]]> Example 15 0.2 <![CDATA[15.38±3.70 ** ]]> Example 20 0.2 <![CDATA[16.88±4.32 ** ]]> Comparative Example 12 0.2 23.75±5.50

[0219] Note: Compared with the blank control group ++P≤0.01; Comparison between model and control groups * P≤0.05, ** P≤0.01.

[0220] As can be seen, compared with the blank control group, the skin appearance score and the number of itching times of mice in the model control group were significantly increased (P≤0.01); compared with the model control group, the skin appearance score and the number of itching times of mice in the treatment groups of Example 10, Example 15 and Example 20 were significantly reduced (P≤0.05 or P≤0.01), and there was no statistically significant difference in the skin appearance score of mice in Comparative Example 12.

[0221] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A prescription for treating radiation dermatitis, characterized in that, By weight percentage, it comprises the following components: 0.01%-2% acetate of peptide compounds, 2-5% primary solvent, 0.05%-1.75% antibacterial agent, 0.5%-3% gel matrix, 0.05%-3% metal ion complexing agent, pH adjuster to adjust pH to 3-7, and the remainder as secondary solvent; The structural formula of the peptide compound is as follows:

2. The drug prescription according to claim 1, characterized in that, The first solvent is selected from one or more of alcohols, amines, dimethyl sulfoxide, diethylene glycol monoethyl ether, fatty acid esters, N-methyl-2-pyrrolidone and tetrahydrofuran polyethylene glycol ether; The alcohol is one or more of propylene glycol, polyethylene glycol, ethanol, isopropanol, 1,3-butanediol, hexanediol, benzyl alcohol, and glycerol; the amine is one or more of dimethylacetamide, ethanolamine, and triethanolamine; and the fatty acid ester is triglyceride and / or isopropyl myristate.

3. The drug prescription according to claim 1, characterized in that, The antibacterial agent is selected from one or more of methylparaben, propylparaben, benzyl alcohol, phenoxyethanol, sorbic acid, benzoic acid, chlorocresol, and chlorobutanol.

4. The drug prescription according to claim 1, characterized in that, The gel matrix is ​​selected from carbomer.

5. The drug prescription according to claim 1, characterized in that, The metal ion complexing agent is selected from disodium edetate.

6. The drug prescription according to claim 1, characterized in that, The pH adjuster is selected from one or more of hydrochloric acid, acetic acid, sodium hydroxide, lactic acid, phosphate buffer, and acetate buffer.

7. The prescription for relieving or treating pruritus according to claim 1, characterized in that, The second solvent is selected from water and / or propylene glycol.

8. A method for preparing the pharmaceutical prescription for treating radiation dermatitis according to any one of claims 1-7, characterized in that, Includes the following steps: (1) Disperse the gel matrix in water, add a metal ion complexing agent and stir to obtain a matrix dispersion; (2) Dissolve the antibacterial agent in the first solvent to obtain an antibacterial solution; (3) The obtained matrix dispersion is mixed with the antibacterial solution, and a gel matrix containing antibacterial agent is obtained by stirring and soaking. (4) Stir the aqueous solution of the acetate of the peptide compound with the obtained gel matrix containing the antibacterial agent, homogenize, add pH adjuster and stir to homogenize, and obtain the drug prescription for treating radiation dermatitis.

9. The use of the pharmaceutical formulation for treating radiation dermatitis according to any one of claims 1-7 in the preparation of a medicament for treating atopic dermatitis and itching.

10. The use of the gel of the pharmaceutical formulation for treating radiation dermatitis according to any one of claims 1-7 in the preparation of a medicament for relieving or preventing skin itching and / or atopic dermatitis caused by radiotherapy.

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