Pyridone endoperoxide with antibacterial and antiviral activity and application thereof

Abstract

The invention discloses pyridone endoperoxide with antibacterial and antiviral activity and application thereof, and belongs to the fields of organic compound synthesis and medical technology, food engineering and the like. The invention proves that the series of endoperoxides can effectively kill pathogenic bacteria, fungi and viruses, including propionibacterium acnes, escherichia coli, staphylococcus aureus, candida albicans, human papilloma viruses, herpes simplex viruses and the like. The internal peroxide designed by the invention has the capability of treating skin diseases, is expected to be developed into a first-line medicine for treating skin diseases caused by pathogen invasion, and mainly relates to bacterial skin diseases, fungal skin diseases and viral skin diseases caused by pathogen infection. Meanwhile, the series of endoperoxides can be used for treating oral infection, periodontitis, infection of shoulder and other joint operations, and bacterial infection such as pressure sores. In addition, the peroxides in the series can also be used in the fields of food preservation, disinfectant preparation and the like.

Description

[0001] The present invention belongs to the fields of organic compound synthesis, pharmaceutical technology, food engineering, etc., and specifically relates to a class of pyridone endoperoxides with antibacterial and antiviral activities and their applications. Background Art

[0002] Microorganisms include bacteria, fungi, and viruses, etc., which play important roles in the environment and human health. However, under certain conditions, the above microorganisms can cause diseases and food contamination, etc. For example, Cutibacterium acnes (C. acnes), a Gram-positive anaerobic bacterium, belongs to the normal skin flora and mainly parasitizes in areas such as sebaceous glands and hair follicles, such as on the face, scalp, chest, and back. The lipase produced by C. acnes can decompose the fat in the sebaceous glands, leading to the blockage of hair follicles and sebaceous glands and triggering acne. In addition, C. acnes is not only associated with suppurative arthritis, discitis, and osteomyelitis, but also often causes infections in the shoulder, hip, or knee during surgery. Escherichia coli can cause skin and soft tissue infections under specific circumstances, such as cellulitis, skin abscess, surgical site infection, pressure ulcer infection, skin diseases accompanied by urinary tract infection, etc. The growth and reproduction of Escherichia coli can lead to food spoilage, producing peculiar smells, abnormal colors, and harmful substances, reducing the quality and safety of food. Foods contaminated with Escherichia coli may cause food poisoning, manifested as diarrhea, vomiting, abdominal pain, and fever, etc. Candida albicans is a common fungus, which can cause cutaneous candidiasis, especially in moist and friction areas, such as the armpit, groin, nail bed, etc., often manifested as redness, eczema-like changes, accompanied by itching and pain. Candida albicans can also cause oral infections, commonly seen on the surface of oral mucosa, especially when the immune system is damaged, manifested as white or cheesy plaques, accompanied by oral pain and a burning sensation. In addition, enveloped viruses such as herpes virus, human papillomavirus, molluscum contagiosum virus, rubella virus, and measles virus endanger human health. Developing effective drugs that can effectively kill bacteria, fungi, and viruses and treat skin diseases caused by these microorganisms is very crucial. At the same time, it is also of great significance to develop disinfectants and food preservatives that can efficiently sterilize. Currently, antibiotics and skin disinfectant drugs cannot effectively inhibit the growth of the above microorganisms, and the research and development of diverse disinfectants and preservatives are an urgent task.

[0003] The cell membrane plays a key role in maintaining the physiological functions of microorganisms, and damaging the cell membrane structure of microorganisms is one of the important directions in the research and development of antibacterial, antifungal, and antiviral drugs. Singlet oxygen ( 1 O 2) Singlet oxygen, namely excited state oxygen molecules, is a class of highly reactive substances that can damage biological molecules such as cell membranes, organelles, and proteins. My previous work has demonstrated that endoperoxides, as singlet oxygen carriers, can simultaneously release singlet oxygen and carrier molecules, which can damage cancer cells, cell membranes, and organelles, leading to apoptosis of cancer cells and showing great potential for anti-cancer. However, the antibacterial, antiviral capabilities of endoperoxides, singlet oxygen, and carrier molecules, as well as their related applications in treating skin diseases and food preservation, have not been studied yet. Summary of the Invention

[0004] The present invention has developed a class of pyridone endoperoxides and demonstrated that a series of endoperoxides can be converted into pyridone derivatives while releasing singlet oxygen and triplet oxygen. The series of endoperoxides can effectively kill bacteria such as Propionibacterium acnes, Escherichia coli, and Staphylococcus aureus, fungi such as Candida albicans, and microorganisms such as human papillomavirus and herpes simplex virus, and have the ability to treat multiple skin diseases. It is expected to be developed into a first-line drug for treating skin diseases caused by pathogen invasion, mainly involving bacterial skin diseases, fungal skin diseases, and viral skin diseases caused by pathogen infections. At the same time, it can be used for the treatment of diseases such as infections after shoulder and other joint surgeries and pressure ulcers. In addition, the series of endoperoxides can also be used in the fields of food preservation and disinfectant preparation.

[0005] The technical solution of the present invention: The application of the compound of formula I or its pharmaceutically acceptable salt in the antibacterial and antiviral fields.

[0006]

[0007] Wherein, R 1 and R 2 are each independently selected from C1-C10 alkyl, C1-C10 deuterated alkyl, -R 1 COOR, -COR 3 , -COOR, -R 1 COR 3 , -CONHR 2 , -R 1 CONHR 2 , nitro, trifluoromethyl, cyano, hydrogen, deuterium.

[0008] R 3 -R 7 are each independently selected from hydrogen, C1-C10 alkyl, C1-C10 deuterated alkyl, C1-C10 fluoroalkyl, C1-C10 alkylamino, -OR 2 , -R 1 OR 2 , sulfonic acid group, sulfonate group, sulfamic acid group, hydroxyl group, amino group, nitro group, cyano group, trifluoromethyl group, halogen, -COOR, -R1 COOR, -R 1 CONHR 2 , -R 1 COR 3 , -CONHR 2 , -COR 3 , -NHCOR 3 ,

[0009] n is an integer from 1 to 5000.

[0010] Each R is independently an alkyl group having 1 to 10 carbon atoms, a deuterated alkyl group having 1 to 10 carbon atoms, H, a sodium ion, a potassium ion, a magnesium ion, a calcium ion, a zinc ion, an aluminum ion, an ammonium ion, or a tetraalkyl quaternary ammonium salt cation.

[0011] R 1 Each is independently an alkylene group having 1 to 10 carbon atoms or a deuterated alkylene group having 1 to 10 carbon atoms.

[0012] R 2 Each is independently an alkyl group having 1 to 10 carbon atoms, a deuterated alkyl group having 1 to 10 carbon atoms, or H.

[0013] R 3 Each is independently an alkyl group having 1 to 10 carbon atoms or a deuterated alkyl group having 1 to 10 carbon atoms.

[0014] In the tetraalkyl quaternary ammonium salt, each alkyl group is independently an alkyl group having 1 to 5 carbon atoms.

[0015] R 4 Each is independently an alkyl group having 1 to 5 carbon atoms, and X - is selected from F - , Cl - , Br - , I - , HSO 4 - , R 5 COO - .

[0016] R 5 Each is independently an alkylene group having 1 to 10 carbon atoms;

[0017] R 6 Each is independently an alkyl group having 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms, or an alkenyl group having 2 to 5 carbon atoms.

[0018] R 7 Each is independently an alkylene group having 1 to 10 carbon atoms.

[0019] In the described application, R 1 , R 2Each independently selected from C1-C5 alkyl, C1-C5 deuterated alkyl, -COR 3 、-COOR,

[0020] -R 1 COR 3 、-R 1 COOR, nitro, trifluoromethyl, cyano, hydrogen, deuterium.

[0021] R 3 -R 7 Each independently selected from hydrogen, C1-C10 alkyl, C1-C10 deuterated alkyl, C1-C10 fluoroalkyl, -OR 2 、-R 1 OR 2 、sulfonic acid group, sulfonate group, sulfamic acid group, hydroxyl group, amino group, nitro group, cyano group, trifluoromethyl group, halogen, -COOR, -R 1 COOR, -R 1 CONHR 2 、-R 1 COR 3 、-CONHR 2 、-COR 3 、-NHCOR 3 、

[0022] n is an integer from 1 to 1000.

[0023] Each R is independently C1-C5 alkyl, C1-C5 deuterated alkyl, H + 、sodium ion, potassium ion, magnesium ion, calcium ion, zinc ion, ammonium ion, tetraalkyl quaternary ammonium salt cation.

[0024] R 1 Each is independently C1-C5 alkylene, C1-C5 deuterated alkylene.

[0025] R 2 Each is independently C1-C5 alkyl, H.

[0026] R 3 Each is independently C1-C5 alkyl.

[0027] The alkyl groups in the tetraalkyl quaternary ammonium salt are each independently alkyl groups having 1 to 3 carbon atoms.

[0028] R 4 Each is independently C1-C3 alkyl, X - is selected from F - 、Cl - 、Br - 、I- 、HSO 4 - 、R 5 COO - 。

[0029] R 5 Each is independently an alkylene group having 1 to 8 carbon atoms.

[0030] R 6 Each is independently an alkyl group having 1 to 3 carbon atoms, an alkoxy group having 1 to 3 carbon atoms, or an alkenyl group having 2 to 3 carbon atoms.

[0031] R 7 Each is independently an alkylene group having 1 to 5 carbon atoms.

[0032] In the said application, R 1 、R 2 Each is independently selected from methyl, trifluoromethyl, deuterated methyl, ethyl, deuterated ethyl, hydrogen, deuterium, -COOR, -COR 3 。

[0033] R 3 -R 7 Each is independently selected from hydrogen, an alkyl group having 1 to 5 carbon atoms, a deuterated alkyl group having 1 to 5 carbon atoms, a fluoroalkyl group having 1 to 5 carbon atoms, a sulfonic acid group, a sulfonate group, a sulfamic acid group, a hydroxyl group, an amino group, -OR 2 、-R 1 OR 2 、nitro, cyano, trifluoromethyl, halogen, -COOR, -NHCOR 3 、-R 1 COOR, -R 1 CONHR 2 、-R 1 COR 3 、-CONHR 2 、-COR 3 、

[0034] n is an integer from 1 to 500.

[0035] Each R is independently an alkyl group having 1 to 5 carbon atoms, H + 、sodium ion, potassium ion, tetramethylammonium cation, tetraethylammonium cation.

[0036] R 1 Each is independently a linear alkylene group having 1 to 5 carbon atoms.

[0037] R 2 Each is independently selected from methyl, ethyl, n-propyl, isopropyl, tert-butyl, n-butyl.

[0038] R 3 Each independently is an alkyl group of C1-C5.

[0039] R 4 Each independently is an alkyl group of C1-C2, X - is selected from F - , Cl - , Br - , I - , HSO 4 - , R 5 COO - .

[0040] R 5 Each independently is an alkylene group of C1-C5.

[0041] R 6 Each independently is an alkyl group of C1-C2, an alkoxy group of C1-C2, an alkenyl group of C2-C3.

[0042] R 7 Each independently is an alkylene group of C1-C5.

[0043] In the said application, R 3 -R 7 Each independently is selected from hydrogen, methyl, deuterated methyl, ethyl, deuterated ethyl, propyl, deuterated propyl, trifluoromethyl, sulfonic acid group, sulfonate group, sulfamic acid group, hydroxyl group, amino group, nitro group, cyano group, trifluoromethyl, halogen, -OR 2 , -R 1 OR 2 , -COOR, -NHCOR 3 , -R 1 COOR, -R 1 CONHR 2 ,

[0044] -R 1 COR 3 , -CONHR 2 , -COR 3 ,

[0045] n is an integer from 1 to 500;

[0046] Each R is independently selected from methyl, ethyl, n-propyl, isopropyl, tert-butyl, sodium ion, potassium ion, magnesium ion, tetramethylammonium cation, tetraethylammonium cation.

[0047] R 1 Each independently is a straight-chain alkylene group of C1-C5.

[0048] R 2 Each is independently selected from methyl, ethyl, n-propyl, isopropyl, tert-butyl, and n-butyl.

[0049] R 3 Each is independently an alkyl group having 1 to 5 carbon atoms.

[0050] R 4 is methyl, and X - is selected from F - 、Cl - 、Br - 、I - 、HSO 4 - 、HCOO - 、CH 3 COO - 。

[0051] R 5 Each is independently methylene, ethylene, propylene, butylene, or pentylene. R 6 Each is independently methyl, ethyl, methoxy, ethoxy, or vinyl.

[0052] R 7 Each is independently methylene, ethylene, propylene, butylene, or pentylene.

[0053] For some specific applications, the compounds of formula I are selected from the following structures:

[0054]

[0055] X - is selected from F - 、Cl - 、Br - 、I - 、HSO 4 -、HCOO - 、CH 3 COO - 。

[0056] For some specific technical solutions, the compounds of formula I can be pharmaceutically common salts, such as hydrochloride, phosphate, sulfate, sodium salt, potassium salt, calcium salt, etc. For the sodium salt, potassium salt, and calcium salt, it refers to the sodium salt, potassium salt, and calcium salt formed by the compound of formula I containing a carboxylic acid group.

[0057] The pharmaceutical dosage form is a gel, cream, solution, spray, aerosol, film, paste, tincture, spirit, lotion, ointment, powder, film-forming agent, oil, plaster, powder, paste, pill, cake, lozenge, microemulsion, patch, cotton pad, lotion, etc. One or more of the above dosage forms are selected for treatment.

[0058] In another aspect of the present disclosure, to improve the antibacterial effect, the combined compound may include at least one of a humectant, a thickener, a surfactant, an emulsion base, a preservative, an antioxidant, an alcohol, a fragrance, a pH regulator, a natural extract, etc., but is not limited thereto. At the same time, it can be a preparation method of cosmetics such as lotion, lotion, cream, shampoo, etc. The above cosmetic composition can be formulated into cosmetics such as softening lotion, astringent lotion, nutritious lotion, nutritious cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, makeup remover, mask, powder, body lotion, body cream, body oil, and body essence, etc., and can also be applied in the form of being applied to the skin or absorbed into the skin interior by means of microneedles, etc.

[0059] The drug includes at least one of the compounds of formula I; and / or a carrier; and / or excipients for cosmetics, pharmaceuticals, and skin products; and / or pharmaceutical excipients; the carrier is selected from one or more of metal nanocarriers, non-metal nanocarriers, liposomes, lactose, sucrose, glucose, gelatin, glycerol, hard magnesium sulfate, stearic acid, sorbitol, mannitol, xylitol, maltitol, starch, gelatin, glycerol, acacia gum, alginate, calcium phosphate, calcium carbonate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methyl paraben, propyl paraben, talc, magnesium stearate, mineral oil, propylene glycol, polyethylene glycol, vegetable oil, injectable esters, Witpsol, polyethylene glycol, tween 61, cocoa butter, lauryl ester, etc.; the pharmaceutical excipients are selected from one or more of gelling agents, active agents, diluents, binders, disintegrants, lubricants, glidants, flavoring agents, coating agents, gelatin capsule shells, cosolvents, propellants, surfactants, preservatives, lyoprotectants, pH regulators, preservatives, wetting agents, conditioning agents, antioxidants, solvents, fragrances, fillers, sunscreens, antibacterial agents, odor absorbers, and pigments, and the drug is prepared into a liposome or micelle form drug.

[0060] According to the application described in the claims, it is characterized in that the drugs disclosed in the present invention can be exemplified as disinfection cleaners, shower foams, ointments, wet wipes, paints, washing soaps, or hand sanitizers, etc., but are not limited thereto. The formulation method, dosage, usage method, constituent components, etc. of quasi-drugs can be appropriately selected from the conventional techniques well-known in the technical field.

[0061] The gelling agent can be polyacrylic acids, polysaccharides, and carboxylic acid polymers, bentonite, aluminum stearate, hydrophobic silica, ethyl cellulose, and polyethylene.

[0062] Specific gelling agents may be selected from at least one of carboxymethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, guar gum, locust bean gum, xanthan gum, clay, carbomer, polyacrylate, polyacrylamide, bentonite, aluminum stearate, hydrophobic silica, ethyl cellulose, and polyethylene.

[0063] Other additives may be selected from urea, glycolic acid, ammonium glycolate, tetramethylammonium glycolate, lactic acid, ammonium lactate, tetramethylammonium lactate, sorbitol, mannitol, xylitol, erythritol, glycerol, hexanetriol, butanetriol, glucose, starch, hyaluronic acid, allantoin, lactamide monoethanolamine, acetamide monoethanolamine, panthenol, saturated C2-C30 fatty alcohols, saturated C2 to C30 diols (such as propylene glycol, butylene glycol, hexylene glycol, polyethylene glycol), saturated C2 to C30 monoglycerides, and saturated C2 to C30 hydroxy fatty acids.

[0064] Activators may be selected from at least one of oligosaccharides, glucose, galactose, xylose, maltose, sucrose, lactose, starch, xylan, hemicellulose, inulin, arabic gum, proteins, hydrolyzed proteins, amino acids, glycerol, sorbitol, butanediol, polyethylene glycol, urea, allantoin, sugars and sugar derivatives, water-soluble vitamins, vitamin C, vitamin E, vitamin A, tocopherol, ceramides and their derivatives, essential oils, β-carotene, lycopene, astaxanthin, lutein, catechol, hesperidin, etc.

[0065] Surfactants are selected from at least one of cetyl polyoxyethylene ethers, cetearyl polyoxyethylene ethers, stearyl polyoxyethylene ethers, PEG-stearates, decanol, cetyl alcohol, stearyl alcohol, lauryl alcohol, myristyl alcohol, oleyl alcohol, sodium dodecyl sulfate, fatty acid soaps, sodium lauryl polyoxyethylene ether sulfate, sodium cetyl polyoxyethylene ether phosphate, and soybean phospholipid (lecithin).

[0066] pH regulators are selected from sodium hydroxide, potassium hydroxide, sodium dihydrogen phosphate, sodium dihydrogen phosphate, sodium bicarbonate, and sodium carbonate.

[0067] Conditioning agents are selected from jojoba oil, soybean oil, canola oil, sunflower oil, safflower oil, rice bran oil, avocado oil, almond oil, olive oil, sesame oil, almond oil, castor oil, coconut oil, and mink oil.

[0068] Specifically, a gelling agent of the present invention includes a high molecular compound, at least one of the compounds of formula I, at least one of a thickener, a crosslinking agent, a humectant, a penetration enhancer, and water.

[0069] Specifically, the high molecular compound is selected from at least one of polyvinylpyrrolidone, polyvinyl alcohol, modified starch, collagen, chitosan, gelatin, carbomer, arabic gum, modified cellulose (such as hydroxyethyl cellulose, carboxymethyl cellulose), and polyacrylamide.

[0070] Specifically, the humectant can be selected from at least one of glycerol, propylene glycol, butylene glycol, pentylene glycol, and polyethylene glycol; the high molecular material can be selected from materials such as sodium alginate, modified starch, collagen, and polyacrylamide, and the binder can be selected from substances such as polyvinylpyrrolidone, polyvinyl alcohol, modified starch, collagen, chitosan, gelatin, carboxymethyl cellulose, carbomer, arabic gum, and hydroxyethyl cellulose.

[0071] Specifically, a cream preparation of the present invention includes a matrix, at least one of the compounds of formula I, and water.

[0072] Among them, the matrix is selected from at least one of commonly used substances for preparing ointments or creams such as glyceryl stearate, alkyl lactate, alkyl citrate, alkyl tartrate, sucrose esters and polyesters, sorbitan esters, starch, sucrose, lactose, mannitol, silicon derivatives, alginates, agar, petrolatum, paraffin wax, liquid paraffin, glycerol, silicone oil, beeswax, stearic acid, lanolin, sodium stearate, triethanolamine, fatty alcohol sulfates, polysorbates (or Tween), cetyl octanoate, octyl isononanoate, tetradecyl lactate, cetyl lactate, isopropyl myristate, tetradecyl myristate, isopropyl palmitate, isopropyl adipate, butyl stearate, decyl oleate, cholesteryl isostearate, fatty alcohols, calcium carbonate, calcium bicarbonate, surfactants, polyethylene glycol, cyclodextrin, β-cyclodextrin, phospholipid materials, kaolin, talc, calcium stearate, magnesium stearate, etc. Specifically, glyceryl stearate is selected from glyceryl monostearate, glyceryl distearate, and glyceryl tristearate.

[0073] Specifically, the drug may further include at least one of bismuth oxychloride, sericite, mica, zeolite, kaolin, silicon dioxide, boron nitride, lauroyl lysine, polyethylene, talc, styrene, polypropylene, polystyrene, ethylene / acrylic acid copolymer, alumina, silicone resin, barium sulfate, calcium carbonate, cellulose acetate, PTFE, polymethyl methacrylate, starch, and modified starch as particulate components.

[0074] Specifically, in the drug, the content of the compound of formula I as an active substance is 0.01% to 80% by weight.

[0075] Specifically, in the drug, the content of the compound of formula I as an active substance is 0.01% to 50% by weight.

[0076] Specifically, in the drug, the content of the compound of formula I as an active substance is 0.5% to about 20% by weight.

[0077] Specifically, in the drug, the content of the compound of formula I as an active substance is 1% to about 15% by weight.

[0078] Specifically, in the drug, the content of the compound of formula I as an active substance is 3% to about 10% by weight.

[0079] The compound of the present invention can effectively kill bacteria such as Propionibacterium acnes, Escherichia coli, Staphylococcus aureus, Streptococcus, Burkholderia furunculosis, Pseudomonas aeruginosa, Clostridium difficile, Bacillus anthracis spores, Pseudomonas, Pseudomonas putrefaciens, etc., fungi such as Candida albicans, dermatophytes, Candida, Aspergillus, Mucor, deep fungi, etc., and viruses such as herpes virus, varicella-zoster virus, human papillomavirus, molluscum contagiosum virus, rubella virus, measles virus, human immunodeficiency virus and other enveloped viruses.

[0080] The compound of the present invention can treat skin diseases such as acne, folliculitis, acne, pustules, papules, cysts, nodules, eczema, boils, flat warts, prickly heat, acne, erysipelas, fasciitis, rosacea, etc.; skin diseases such as tinea capitis, tinea manus and pedis, dermatophytosis, tinea corporis and cruris, pityriasis versicolor, onychomycosis, pityriasis versicolor, pityriasis versicolor, hypertrophic scar, nevus flammeus, condyloma acuminata, skin photoaging, psoriasis, erythroderma squamosa disease, etc.; viral skin diseases such as herpes simplex, varicella, verrucous lesions, rubella, measles, hand, foot and mouth disease, HPV infection, etc.

[0081] The compound of the present invention can be used for the treatment of diseases such as oral infections, periodontitis, shoulder and other joint surgical infections, pressure sore infections, etc.

[0082] The compound of the present invention can be used for applications such as disinfection, food preservation, etc.

[0083] The above-mentioned compound can be used alone or in combination with one or more other drugs during the treatment process.

[0084] The compound of formula I can be used in combination with other oral, injectable, and topical drugs to treat the diseases described in the claims.

[0085] The present invention provides an internal peroxide gel, which comprises the following components by weight:

[0086] The compound according to any one of claims 1-6: 0.1-10%;

[0087] Purified water: 60-90%;

[0088] Gelling agent: 0-5%;

[0089] Emollient: 0 - 5%;

[0090] Humectant: 0 - 10%;

[0091] Thickener: 0 - 3%;

[0092] Preservative: 0 - 1%;

[0093] Antioxidant: 0 - 0.5%;

[0094] Excipient: 0 - 5%;

[0095] Stabilizer: 0 - 2%;

[0096] pH regulator: 0 - 1%;

[0097] Fragrance: 0 - 1%;

[0098] Pigment: 0 - 0.1%;

[0099] The gelling agent is selected from xanthan gum, carob gum, carbomer, sodium polyacrylate, hydroxypropyl methylcellulose, poloxamer 182, carbomer 940, sodium docusate, disodium edetate, silicon dioxide, polyvinyl alcohol (PVA), hydroxypropyl methylcellulose, sodium alginate, chitosan, gelatin, collagen, montmorillonite, polyurethane, polyacrylamide and other common gelling matrices;

[0100] The emollient is selected from mineral oil, vegetable oil, jojoba oil, avocado oil, glycerin, sodium lactate, glycerol, propylene glycol, polyethylene glycol, urea, hyaluronic acid, panthenol, lactic acid, glycyrrhizic acid, squalane, vegetable oil (such as coconut oil, almond oil, olive oil), honey extract, aloe extract;

[0101] The humectant is selected from mineral oil, vegetable oil, jojoba oil, avocado oil, glycerin, sodium lactate, glycerol, propylene glycol, polyethylene glycol, urea, hyaluronic acid, panthenol, lactic acid, glycyrrhizic acid, squalane, vegetable oil (such as coconut oil, almond oil, olive oil), honey extract, aloe extract;

[0102] The thickener is selected from xanthan gum, carboxymethyl cellulose, sodium carboxymethyl cellulose, methyl cellulose, sodium alginate, guar gum, acrylate copolymer, polyvinyl alcohol, polyacrylamide, gelatin, collagen, bentonite, silica gel, carbomer, hydroxypropyl methylcellulose, etc.;

[0103] The preservative is selected from benzoic acid, sodium benzoate, parabens, methyl paraben, propyl paraben, ethyl paraben, butyl paraben, phenoxyethanol, benzyl alcohol, sorbic acid and its salts, benzalkonium chloride, ethanol, methylisothiazolinone, diazolidinyl urea, dihydroxy toluene dialdehyde, caprylyl glycol, chlorphenesin;

[0104] The antioxidant is selected from vitamin E, tocopherol, ascorbic acid, sodium ascorbyl phosphate, butylated hydroxytoluene, butylated hydroxyanisole (BHA), coenzyme Q10, green tea extract, resveratrol, lipoic acid, grape seed extract, rosemary extract, α-tocopheryl acetate, quercetin, etc.;

[0105] The excipient is water, alcohols, glycerin, propylene glycol, polyethylene glycol, polyacrylamide, carbomer, hydroxypropyl methylcellulose, sodium alginate, xanthan gum, gelatin, chitosan, silicon dioxide, triglyceride, dimethyl silicone oil;

[0106] The stabilizer is sodium EDTA, carbomer, xanthan gum, hydroxypropyl methylcellulose, sodium alginate, polyethylene glycol, gelatin, chitosan, silicon dioxide, sodium carboxymethylcellulose, polyacrylamide, triethanolamine, sodium hydroxide, citric acid and its salts, EDTA (ethylenediaminetetraacetic acid) and its salts;

[0107] The pH regulator is selected from triethanolamine, lactic acid, citric acid, acetic acid, phosphoric acid, sodium carbonate, sodium bicarbonate, sodium citrate, sodium lactate, sodium hydroxide, potassium hydroxide.

[0108] The present invention provides an endoperoxide ointment, which comprises the following components by weight:

[0109] The compound according to any one of claims 1-6: 0.5-22%;

[0110] Matrix: 60-90%;

[0111] Emollient: 0-5%;

[0112] Thickener: 0-3%;

[0113] Preservative: 0-1%;

[0114] Antioxidant: 0-0.5%;

[0115] Excipient: 0-5%;

[0116] Stabilizer: 0-2%

[0117] Fragrance: 0-1%;

[0118] Pigment: 0 -0.1%;

[0119] The matrix is selected from petrolatum, lanolin, vegetable oil, olive oil, almond oil, coconut oil, beeswax, polyethylene glycol, propylene glycol, glycerin, carbomer, stearyl alcohol, paraffin wax, glyceryl monostearate, sodium lauryl sulfate, glycerin, ethylparaben, span-40, emulsifier OP, ethylparaben, stearic acid, white paraffin, liquid paraffin, white soft paraffin, beeswax, vegetable oil, glyceryl monostearate, polyethylene glycol, white petrolatum, higher alcohols and other common ointment matrices

[0120] The emollient is selected from mineral oil, petrolatum, vegetable oil, lanolin, squalane, urea, amino acid, polyethylene glycol, beeswax, hyaluronic acid, plant extracts (such as aloe extract, green tea extract), shea butter, jojoba oil, avocado oil, glycerol, sodium lactate;

[0121] The thickener is selected from xanthan gum, gelatin, emulsifying wax, colloidal silicon, hydrogenated polyisobutene, sodium carboxymethyl cellulose, carboxymethyl cellulose, polyvinyl alcohol, polyacrylamide, carbomer, hydroxypropyl methylcellulose, hydroxyethyl cellulose;

[0122] The preservative is selected from sodium benzoate, parabens, methyl paraben, ethyl paraben, propyl paraben, butyl paraben, phenoxyethanol, benzyl alcohol, potassium sorbate, benzalkonium chloride, methylisothiazolinone, imidazolidinyl urea, dihydroxytoluene dimethylformaldehyde, caprylyl glycol, chlorphenesin, ammonium acetate;

[0123] The antioxidant is selected from tocopherol, ascorbic acid, vitamin E, sodium ascorbyl phosphate, coenzyme Q10, resveratrol, green tea extract, lipoic acid, grape seed extract, rosemary extract, quercetin, β-carotene, tocopheryl acetate;

[0124] The excipient is xanthan gum, mineral oil, petrolatum, lanolin, vegetable oil, shea butter, polyvinyl alcohol, emulsifying wax, alcohols, glycerol, propylene glycol, polyethylene glycol, polyacrylamide, carbomer, hydroxypropyl methylcellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, hydrogenated polyisobutene, sodium alginate, xanthan gum, gelatin, chitosan, silicon dioxide, triglyceride, dimethicone;

[0125] The stabilizer is vitamin E, BHT, BHA, polysorbate, stearic acid, glycerol monostearate, EDTA and its salts, citric acid and its salts, phosphates, liposomes, sodium dodecyl sulfate, polyethylene glycol.

[0126] The present invention provides an endoperoxide cream, which comprises the following components by weight:

[0127] The compound according to any one of claims 1-6: 0.5-10%;

[0128] Matrix: 70-90%;

[0129] Emollient: 0-30%;

[0130] Thickener: 0-3%;

[0131] Preservative: 0-1%;

[0132] Antioxidant: 0-0.5%;

[0133] Excipient: 0 - 5%;

[0134] Stabilizer: 0 - 2%

[0135] Fragrance: 0 - 1%;

[0136] Colorant: 0 - 0.1%;

[0137] The matrix is selected from water, urea, petrolatum, lanolin, mineral oil, vegetable oil, olive oil, almond oil, coconut oil, beeswax, polyethylene glycol, propylene glycol, glycerol, carbomer, stearyl alcohol, paraffin wax, stearic acid, triglyceride, glycerol monostearate, sodium lauryl sulfate, glycerol, ethylparaben, span - 40, emulsifier OP, PEG - 100 stearate, ethylparaben, stearic acid, white paraffin, liquid paraffin, white soft paraffin, beeswax, vegetable oil, glycerol monostearate, carbomer, xanthan gum, hydroxypropyl methylcellulose, hydroxyethyl cellulose, parabens, phenoxyethanol, potassium sorbate, polysorbates, glycerol monostearate, cetearyl alcohol, polyethylene glycol, white petrolatum, higher alcohols and other common cream matrices

[0138] The emollient is selected from mineral oil, petrolatum, olive oil, coconut oil, vegetable oil, shea butter, jojoba oil, almond oil, avocado oil, glycerol, sodium lactate, cetearyl alcohol, stearyl alcohol, triglyceride, caprylic / capric triglyceride, glycerol monostearate, stearic acid glyceride, propylene glycol, urea, aloe extract, oat extract, honey extract, etc.;

[0139] The thickener is selected from xanthan gum, guar gum, gum arabic, carrageenan, carboxymethyl cellulose, carbomer, hydroxypropyl methylcellulose, hydroxyethyl cellulose, polyvinyl alcohol, methylcellulose, cetearyl alcohol, stearyl alcohol, cetyl alcohol, emulsifying wax, bentonite, yellow wax, microcrystalline wax, etc.;

[0140] The preservative is selected from sodium benzoate, phenoxyethanol, potassium sorbate, sodium benzoate, parabens, methylparaben, ethylparaben, propylparaben, butylparaben, methylisothiazolinone, methylchloroisothiazolinone, benzyl alcohol, caprylyl glycol, ethylhexylglycerin, diazolidinyl urea, imidazolidinyl urea, chlorphenesin, triclocarban, grapefruit seed extract, tea tree oil;

[0141] The antioxidant is selected from vitamin E, vitamin C, vitamin A, BHT, BHA, EDTA and its salts, tocopherol, ascorbic acid, green tea extract, grape seed extract, rosemary extract, coenzyme Q10, carotene, glutathione, resveratrol, catechin, citric acid, malic acid;

[0142] The excipients are xanthan gum, mineral oil, petrolatum, lanolin, vegetable oil, shea butter, polyvinyl alcohol, emulsifying wax, alcohols, glycerin, propylene glycol, polyethylene glycol, polyacrylamide, carbomer, hydroxypropyl methylcellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, hydrogenated polyisobutene, sodium alginate, xanthan gum, gelatin, chitosan, silicon dioxide, triglyceride, dimethicone;

[0143] The stabilizers are vitamin E, BHT, BHA, polysorbate, stearic acid, glycerol monostearate, EDTA and its salts, citric acid and its salts, phosphates, liposomes, sodium dodecyl sulfate, polyethylene glycol.

[0144] The present invention provides an internal peroxide disinfectant, which comprises the following components by weight:

[0145] The compound according to any one of claims 1-6: 0.5-10%;

[0146] Water: 86-99.4%;

[0147] Stabilizer: 0.1%-1%;

[0148] pH regulator: 0%-0.5%;

[0149] Preservative: 0%-0.5%;

[0150] Emulsifier: 0%-1%;

[0151] Surfactant: 0%-0.1%;

[0152] The stabilizers are citric acid and its salts, phosphates, acetic acid and its salts, ethylenediaminetetraacetic acid (EDTA) and its salts, citric acid, ascorbic acid, sodium thiosulfate, ethanol, isopropanol, glycerin, propylene glycol, polysorbate, phenoxyethanol, parabens, sodium bicarbonate, sodium chloride, etc.

[0153] The pH regulators are selected from triethanolamine, lactic acid, citric acid, acetic acid, phosphoric acid, sodium carbonate, sodium bicarbonate, sodium citrate, sodium lactate, sodium hydroxide, potassium hydroxide.

[0154] The preservatives are phenoxyethanol, parabens, potassium sorbate, benzoates;

[0155] The emulsifiers are polysorbate 20, polysorbate 80, span 60, span 80, cetearyl alcohol, stearyl alcohol, polyoxyethylene fatty alcohol ether, Ceteareth-20, polyethers, phosphodiesters, cyclosiloxanes, lecithin, polyethylene glycol;

[0156] The surfactant is selected from polysorbate, ceteth, sodium alkylbenzene sulfonate, quaternary ammonium salts, betaine, sodium dodecyl sulfate, octylphenol polyoxyethylene ether, phytosterol polyoxyethylene ether.

[0157] Specifically, the compounds of formula I are selected from the following structures:

[0158]

[0159] X - is selected from F - , Cl - , Br - , I - , HSO 4 -, HCOO - , CH 3 COO - .

[0160] The preparation method of the compound of formula I comprises the following steps:

[0161]

[0162] (1) Compound 1 and compound 2 react in the presence of potassium carbonate and copper(I) iodide to obtain compound P;

[0163] (2) Compound P reacts under the conditions of a photosensitizer, an oxygen environment, and light irradiation to obtain compound E.

[0164] In some specific preparation methods, the reaction solvent in step (1) is one or more of high-boiling solvents such as N,N-dimethylformamide and dimethyl sulfoxide. The reflux reaction temperature is between 150 - 200 °C. The amounts of iodobenzene 2 and potassium carbonate are 1 - 3 times (molar amount) that of 2-pyridone. The amount of cuprous iodide is 2% - 20% (molar amount) of 2-pyridone. In some specific preparation methods, the reaction solvent in step (2) can be one or more of solvents such as chloroform, dichloromethane, ether, methanol, ethanol, toluene, benzene, DMF, ethyl acetate, water, deuterated reagents, etc. The reaction temperature is -20 °C to room temperature, preferably ice-water bath, 0 °C, ice bath, room temperature water bath or below 0 °C. Reaction can occur at room temperature, but care should be taken to prevent high-temperature evaporation of the solvent under red light irradiation. Other light sources with wavelengths of 425 - 750 nm can also be used. The gas environment can be introducing oxygen, oxygen-containing gas into the reaction vessel or directly reacting with an open mouth. Methylene blue / red light can be replaced by other common photosensitizers and corresponding wavelength light sources, such as BODIPY / red light, etc. The deuterated reagent is selected from one or several of deuterated chloroform, deuterated methanol, deuterated benzene, and deuterated water; the photosensitizer is selected from methylene blue, boron-dipyrromethene, hematoporphyrin, chlorin e6, pyropheophorbide-a, pyropheophorbide a hexyl ether, phenothiazine derivatives, phenoxazine derivatives, porphyrin photosensitizers or phthalocyanine photosensitizers.

[0165] The treatment mechanism of the compound is as follows: Endoperoxide E is converted into precursor P in vivo, while singlet oxygen and triplet oxygen are released, and the three components act separately or jointly. In addition, endoperoxide E itself also has a therapeutic effect.

[0166]

[0167] Advantages and beneficial effects of the present invention: The endoperoxides provided by the present invention can be batch-prepared through a simple chemical synthesis method, and at the same time have good stability and can be stored for a long time. This type of endoperoxide integrates multiple therapeutic factors such as endoperoxide, pyridone, singlet oxygen, and triplet oxygen, that is, it can exert the therapeutic effects of a single factor and at the same time achieve the purpose of synergistic treatment of several factors. The series of compounds can effectively kill bacteria such as Propionibacterium acnes, Escherichia coli, Staphylococcus aureus, Streptococcus, Burkholderia furunculosis, Pseudomonas aeruginosa, Clostridium difficile, Bacillus anthracis spores, Pseudomonas, Pseudomonas putrefaciens, etc., fungi such as Candida albicans, dermatophytes, Candida spp., Aspergillus spp., Mucor spp., deep fungi, etc., and enveloped viruses such as herpes virus, varicella-zoster virus, human papillomavirus, molluscum contagiosum virus, rubella virus, measles virus, human immunodeficiency virus, etc. The series of compounds can treat skin diseases including acne, folliculitis, acne, pustules, papules, cysts, nodules, eczema, boils, flat warts, prickly heat, acne vulgaris, erysipelas, fasciitis, rosacea, etc.; skin diseases such as tinea capitis, tinea manus et pedis, fungal dermatitis, tinea corporis et cruris, pityriasis versicolor, onychomycosis, pityriasis versicolor, pityriasis versicolor, hypertrophic scar, nevus flammeus, condyloma acuminata, skin photoaging, psoriasis, erythroderma-squamous diseases, etc.; viral skin diseases such as herpes simplex, chickenpox, verrucous lesions, rubella, measles, hand-foot-and-mouth disease, HPV infection, etc. At the same time, it can be used for the treatment of bacterial infections such as shoulder and other joint surgical infections, pressure sores, etc. The endoperoxides involved in the present invention can be used for applications such as disinfection and food preservation, and are healthy and safe, with small toxic and side effects and no drug resistance. Description of the Drawings

[0168] Figure 1 is the 1H NMR spectrum of the representative compound E1 of the present invention.

[0169] Figure 2 is the 1H NMR spectrum of the representative compound E11 of the present invention.

[0170] Figure 3 is the singlet oxygen release experiment (using DPBF as a probe) of the representative compound E1 of the present invention.

[0171] Figure 4 is the singlet oxygen release experiment (using DPBF as a probe) of the representative compound E11 of the present invention.

[0172] Figure 5 is the singlet oxygen release experiment and half-life test (1H NMR spectrum) of the representative compound E5 of the present invention.

[0173] Figure 6 is the singlet oxygen release ratio test experiment (using tetramethylethylene as a probe) of the representative compound E5 of the present invention.

[0174] Figure 7 These are the experimental results of the representative compounds E3, E11, E12, E33 and the control BPO against Propionibacterium acnes.

[0175] Figure 8 These are the experimental results of the representative compound E11 and the raw material P11 against Propionibacterium acnes.

[0176] Figure 9 These are the experimental results of the representative compounds E1, E4, E5, E8, E30 against Escherichia coli.

[0177] Figure 10 These are the structure and antibacterial experimental result diagrams of pyridone endoperoxides. Detailed implementation manners

[0178] The present invention relates to a preparation method of pyridone endoperoxides, and the synthetic route is as follows:

[0179]

[0180] (1) Place 2-pyridone 1, iodobenzene 2, potassium carbonate, copper iodide and DMF in a reaction flask, and reflux the reaction under argon protection. After the reaction is completed, cool to room temperature, filter by suction, and add activated carbon to the filtrate for decolorization. Evaporate the decolorized solution to dryness under reduced pressure, add 10% acetic acid, and stir at 70 °C. After standing for liquid separation, take the upper aqueous phase and adjust the pH to 13 with sodium hydroxide solution, and place it in the refrigerator overnight for crystallization. Heat the obtained crude product to reflux with ethyl acetate, filter by suction while it is hot, and cool the filtrate for crystallization. Filter by suction, and dry the filter cake under reduced pressure to obtain the pure product P.

[0181] (2) Place the compound P, a catalytic amount of methylene blue and chloroform in a reaction flask, irradiate with red light (620 - 625 nm) under oxygen protection, stir in an ice-water bath, and monitor the reaction by TLC. After the reaction is completed, filter off methylene blue using silica gel (or activated carbon) by suction. Evaporate the obtained filtrate to dryness under reduced pressure to obtain the pure product compound E.

[0182] Example 1: Synthetic methods of the representative compounds E1 and E11

[0183]

[0184] Compound 1a (10 g), iodobenzene 2a (1.5 equiv.), potassium carbonate (1.1 equiv.), copper(I) iodide (10 mol%), and DMF (300 mL) were placed in a 500 mL reaction flask. Under argon protection, the mixture was refluxed at 150 °C for 10 hours. After the reaction was completed, it was cooled to room temperature, filtered by suction. The filter cake was washed three times with DMF, and the filtrates were combined. Activated carbon was added for decolorization. The decolorized solution was evaporated to dryness under reduced pressure, 100 mL of 10% acetic acid was added, and the mixture was stirred at 70 °C for 30 minutes. After standing for phase separation, the upper aqueous phase was taken. The lower oily substance was extracted twice with 10% acetic acid, and the aqueous phases were combined. The aqueous phase was adjusted to pH 13 with sodium hydroxide solution and allowed to crystallize overnight in the refrigerator. 100 mL of ethyl acetate was added to the crude product obtained by drying under reduced pressure, heated to reflux, filtered by suction while hot, and the filtrate was cooled to crystallize. Filtration was carried out by suction, and the filter cake was dried under reduced pressure to obtain the pure product P1. Compound P1 (5 g), methylene blue (5 mg), and chloroform (100 mL) were placed in a reaction flask. Under oxygen protection, it was irradiated with red light (620 - 625 nm), stirred in an ice-water bath, and the reaction was monitored by TLC. After the reaction was completed, methylene blue was removed by filtration with silica gel (or activated carbon) by suction, and the filtrate was evaporated to dryness under reduced pressure to obtain compound E1. Yield: 100%. 1 H NMR (400 MHz, CDCl 3 ) δ 7.22–7.17 (m, 4H), 6.96–6.92 (m, 1H), 6.58–6.56 (m, 1H), 6.02–6.00 (m, 1H), 2.35 (s, 3H), 1.69 (s, 3H).( Figure 1 )

[0185]

[0186] Route 1: Place compound 1a (10 g), iodobenzene 2b (1.5 equiv.), potassium carbonate (2.1 equiv.), copper(I) iodide (10 mol%), and DMF (300 mL) in a 500 mL reaction flask. Under argon protection, reflux the reaction mixture at 150 °C for 10 hours. After the reaction is completed, cool the mixture to room temperature, filter by suction, wash the filter cake three times with DMF, combine the filtrates, and add activated carbon for decolorization. Evaporate the decolorized solution to dryness under reduced pressure, add 100 mL of 10% acetic acid, and stir at 70 °C for 30 minutes. After standing for liquid separation, take the upper aqueous phase, extract the lower oily substance twice with 10% acetic acid, and combine the aqueous phases. Adjust the pH of the aqueous phase to 13 with sodium hydroxide solution and place it in the refrigerator overnight for crystallization. Add 100 mL of ethyl acetate to the crude product obtained by drying under reduced pressure, heat to reflux, filter by suction while hot, and cool the filtrate for crystallization. Filter by suction, and dry the filter cake under reduced pressure to obtain the pure product P11. Place compound P11 (5 g), methylene blue (5 mg), and chloroform (100 mL) in a reaction flask. Under oxygen protection, irradiate with red light (620 - 625 nm), stir in an ice-water bath, and monitor the reaction by TLC. After the reaction is completed, filter off methylene blue using silica gel (or activated carbon) by suction, and evaporate the filtrate to dryness under reduced pressure to obtain compound E11.

[0187] Route 2: Place compound 1a (10 g), ethyl 4-iodobenzoate 2c (1.5 equiv.), potassium carbonate (2.0 equiv.), copper(I) iodide (10 mol%), and DMF (300 mL) in a 500 mL reaction flask. Under argon protection, reflux the reaction mixture at 150 °C for 6 hours. After the reaction is completed, evaporate the solvent under reduced pressure, add an appropriate amount of ice water to the residue, extract 3 times with ethyl acetate, combine the lower organic phases, wash once with saturated brine, dry with anhydrous sodium sulfate, and concentrate the filtrate. The crude product is separated by silica gel column chromatography to obtain compound P12. Yield: 82%. Dissolve NaOH (2 - 5 equiv.) in an EtOH / H 2 O (120 mL, 3 / 1 - 5 / 1) system, and slowly add it to a solution of compound P12 (1 g) at 0 °C. Reflux the reaction mixture at 83 °C for 5 hours. After the reaction is completed, evaporate ethanol under reduced pressure, wash the residue once with ethyl acetate, extract the organic phase 3 times with water, and combine the aqueous phases. Adjust the pH of the aqueous phase to 2 with hydrochloric acid solution and place it in the refrigerator overnight for crystallization. Filter by suction, and dry the filter cake under reduced pressure to obtain the pure product P11, with a yield of 96%. Place compound P11 (5 g), methylene blue (5 mg), and chloroform (100 mL) in a reaction flask. Under oxygen protection, irradiate with red light (620 - 625 nm), stir in an ice-water bath, and monitor the reaction by TLC. After the reaction is completed, filter off methylene blue using silica gel (or activated carbon) by suction, and evaporate the filtrate to dryness under reduced pressure to obtain compound E11. Yield: 98 - 100%. 1 H NMR (400 MHz, CDCl 3)δ 8.07 (d, J = 8.5 Hz, 2H), 7.48 (d, J = 8.5 Hz, 2H), 7.07–7.04 (m, 1H), 6.68–6.65 (m, 1H), 6.54–6.52 (m, 1H), 1.60 (s, 3H).( Figure 2 )

[0188] In the examples of the present invention, the preparation of other compounds refers to the preparation steps of Example 1. Since the structures of most compounds have been disclosed in the Chinese invention patent with the publication number CN116655654A, they will not be elaborated in this application.

[0189]

[0190]

[0191] Example 2: Test on the drug delivery ability of endoperoxides

[0192] Singlet oxygen trapping experiment: Using DPBF as a singlet oxygen trapping reagent, the release of singlet oxygen by the compound was monitored. The experimental procedure was as follows: Representative compounds such as E1 or E11 (750 μM) and DPBF (singlet oxygen scavenger, 37.5 μM) were dissolved in DMF. At 37 °C under dark conditions, the absorption at 417 nm was monitored using a UV-visible spectrophotometer at different time intervals to analyze the release of singlet oxygen. The results showed that endoperoxides could efficiently release singlet oxygen (as Figures 3 - 4 shown).

[0193] Drug release half-life: Endoperoxides release raw materials, singlet oxygen, and triplet oxygen through a retro-cycloaddition reaction. The whole process follows the first-order kinetic rate equation, and the half-life can be calculated by the formula t 1 / 2 = 0.693 / k. The representative experimental procedure was as follows: Weigh approximately 2 mg of endoperoxide E5 and dissolve it in deuterium water, then place it in a water bath at 37 °C. The 1H NMR spectra of the solution were measured at 6 hours, 10 hours, 23 hours, and 35 hours respectively. The half-life of the retro-cycloaddition reaction was calculated through the characteristic peaks of E5 and P5 between 6.25 - 6.75 ppm: t 1 / 2 = 11.9 hours (at 37 °C, in deuterium water, as Figure 5 shown).

[0194] Drug release yield: Using tetramethylethylene as a singlet oxygen trapping reagent, the drug release yield of endoperoxides was calculated using 1H NMR spectra according to the above method. Taking endoperoxide E5 as an example, the results showed that after 1 mole of E5 underwent a complete reverse reaction, 1 mole of P5, 0.5 mole of singlet oxygen, and 0.5 mole of triplet oxygen were released (as Figure 6 shown).

[0195] Example 3: Preparation of an internal peroxide gel

[0196] Dissolve poloxamer 182 (15 g), carbomer 940 (1 g), sodium docusate (0.2 g), disodium edetate (0.05 g), glycerol (8 g), silicon dioxide (0.5 g), an appropriate amount of solid sodium hydroxide (for adjusting the pH to between 6 and 7), and propylene glycol (10 g) in purified water (64.25 g). Stir rapidly to dissolve and disperse evenly, and place in a 4°C refrigerator overnight until completely swollen. Then gradually add the solution obtained by dissolving acrylate copolymer (AC, 3 g) and internal peroxide (such as E11, 5 g) in ethanol (15 g), add an appropriate amount of purified water, and stir evenly to obtain a transparent gel.

[0197] The above ratios can be adjusted according to specific requirements and applications to ensure the effectiveness and stability of the gel. The present invention is not limited to the described gel preparation method, and any other relevant gel preparation methods, ingredient compositions, ratios, etc. applicable to the drugs of the present invention are also within the protection scope of the present invention.

[0198] Example 4: Preparation of an internal peroxide ointment

[0199] Oily matrix internal peroxide ointment: Place the internal peroxide in a mortar and grind it finely. Weigh 0.5 g for standby. Separately, mix petrolatum (84.5 g) and liquid paraffin (15 g) evenly on an ointment slab to obtain an oily matrix, and then mix the finely ground internal peroxide (such as E11) with the above matrix evenly.

[0200] The above ratios can be adjusted according to specific requirements and applications to ensure the effectiveness and stability of the ointment. The present invention is not limited to the described ointment preparation method, and any other relevant ointment preparation methods, ingredient compositions, ratios, etc. applicable to the drugs of the present invention are also within the protection scope of the present invention.

[0201] Water-soluble matrix internal peroxide ointment: Place sodium carboxymethylcellulose (2 g) in a mortar, add glycerol (10 g) and grind evenly, then while grinding, add the aqueous solution (87 g) containing sodium benzoate (0.5 g). After swelling for 15 minutes, grind evenly to obtain a water-soluble matrix, and then mix the finely ground internal peroxide (such as E11, 0.5 g) with the above matrix evenly.

[0202] The above ratios can be adjusted according to specific requirements and applications to ensure the effectiveness and stability of the ointment. The present invention is not limited to the described ointment preparation method, and any other relevant ointment preparation methods, ingredient compositions, ratios, etc. applicable to the drugs of the present invention are also within the protection scope of the present invention.

[0203] Example 5: Preparation of an internal peroxide cream

[0204] Preparation of O / W-type internal peroxide cream: Take white petrolatum (15 g), cetyl alcohol (3 g) and glyceryl monostearate (3 g) and place them in an evaporating dish. Heat in a water bath to 70 - 80 °C until melted. Place sodium lauryl sulfate (1 g), glycerol (5 g), ethylparaben (0.2 g) and purified water (67.8 g) in another evaporating dish and heat to 70 - 80 °C until dissolved. At the same temperature, add the aqueous solution to the oily solution in a thin stream, stirring continuously until it condenses to obtain an O / W emulsion base. Take the finely ground internal peroxide (such as E11, 5 g) and place it on an ointment slab (or in a mortar), and add the prepared O / W emulsion base in portions and mix well (grind evenly) to obtain the product.

[0205] The above ratios can be adjusted according to specific requirements and applications to ensure the effect and stability of the cream. The present invention is not limited to the preparation method of the described cream, and any other relevant cream preparation methods applicable to the drugs of the present invention, or ingredient compositions, ratios, etc. are also within the protection scope of the present invention.

[0206] Preparation of W / O-type internal peroxide cream: Take paraffin wax (30 g), glyceryl monostearate (4 g), white petrolatum (15 g), liquid paraffin (7 g), span - 40 (3 g), emulsifier OP (5 g) and ethylparaben (0.3 g) in an evaporating dish, heat and melt on a water bath and maintain at 80 °C, and add water (36.7 g) at the same temperature in a thin stream, stirring continuously until it condenses to obtain a W / O emulsion base. Take the finely ground internal peroxide (such as E11, 4 g) and place it on an ointment slab or in a mortar, and add the prepared W / O emulsion base in portions and mix well (grind evenly) to obtain the product.

[0207] The above ratios can be adjusted according to specific requirements and applications to ensure the effect and stability of the cream. The present invention is not limited to the preparation method of the described cream, and any other relevant cream preparation methods applicable to the drugs of the present invention, or ingredient compositions, ratios, etc. are also within the protection scope of the present invention.

[0208] Example 6: Preparation of internal peroxide disinfectant

[0209] Take purified water (95 g) and add it to a conical flask. Dissolve 5 g of internal peroxide (E5 or E11) in appropriate glycerol (10 g), slowly add it to the conical flask, and stir at room temperature for immediate use.

[0210] The main component of the disinfectant involved in the present invention is an internal peroxide, usually at a concentration of 0.1 - 5%, depending on the specific use. A certain amount of ethanol, glycerol, or PEG, etc. is used as an auxiliary component to adjust the texture of the disinfectant and the solubility of the internal peroxide. The above ratios can be adjusted according to specific requirements and applications to ensure the effectiveness and stability of the disinfectant. The present invention is not limited to the preparation method of the described disinfectant, and any other preparation method applicable to the disinfectant of the present invention, or the ingredient composition, ratio, etc. are also within the protection scope of the present invention.

[0211] Example 7: Preparation of the internal peroxide preservative

[0212] The main component of the internal peroxide preservative is an internal peroxide, and the usage methods can be divided into direct addition: adding the internal peroxide directly into the food in the form of powder or solution and mixing evenly. For example, in fruit juices, beverages, and seasonings, the internal peroxide is often directly added in liquid form.

[0213] Surface treatment: For some foods vulnerable to surface contamination, surface treatment can be carried out by spraying or smearing the internal peroxide solution. For example, bakery foods such as bread and cakes can be sprayed with the internal peroxide solution to prevent mold growth.

[0214] Soaking: Some foods need to be soaked in the internal peroxide solution during the processing to achieve the anti-corrosion effect. For example, fruits and vegetables can be soaked in the internal peroxide preservative solution for a short time and then further processed and packaged.

[0215] Adding in packaging: Some foods add the internal peroxide preservative during packaging to extend the shelf life. This method is usually used for packaged and sealed foods such as meat products and dairy products.

[0216] Combined use: In order to enhance the anti-corrosion effect, multiple preservatives are often used in combination. For example, the internal peroxide is combined with one or more of other anti-corrosion components such as benzoic acid, sorbic acid, nitrates, nitrites, etc.

[0217] Dosage control: The addition amount of the internal peroxide preservative must be strictly controlled within the range permitted by regulations to ensure food safety. Uniform distribution: The preservative must be uniformly distributed in the food to ensure the anti-corrosion effect of the whole food. Scope of application: The internal peroxide preservative is not only applicable to foods required by humans and animals, but also applicable to medicines and other items that need to ensure quality through antibacterial.

[0218] Example 8: Microbial killing experiment

[0219] Streak the Propionibacterium acnes strain on a GAM agar plate and place it in a 37°C constant temperature incubator for anaerobic culture for 7 days. After obtaining single colonies, pick one of the single colonies and inoculate it into a 50 mL centrifuge tube containing 30 mL of GAM broth. Place it on a shaker at 37°C (190 rpm) for anaerobic culture for 7 days. Salt drugs are dissolved in the bacterial solution, and other drugs are dissolved in DMSO to prepare a stock solution with a concentration of 50 mM. The bacterial solution after drug administration (0.5 mM, final concentration) is placed in a 37°C constant temperature incubator for anaerobic culture for 4 days. After serial dilution of the bacterial solution after drug administration, take 50 μL and evenly spread it on a GAM agar medium plate with a sterile spreading rod. After anaerobic culture at 37°C for 7 days, take a photo and perform colony counting.

[0220] Streak the Escherichia coli strain on an LB agar plate and place it in a 37°C constant temperature incubator for 16 h. After obtaining single colonies, pick one of the single colonies and inoculate it into a 50 mL centrifuge tube containing 25 mL of LB broth. Place it on a shaker at 37°C (190 rpm) for 24 h. Salt drugs are dissolved in the bacterial solution, and other drugs are dissolved in DMSO to prepare a stock solution with a concentration of 250 mM. The bacterial solution after drug administration (2.5 mM, final concentration) is placed in a 37°C constant temperature incubator for 24 h. Take 50 μL and evenly spread it on an LB agar medium plate with a sterile spreading rod. After culture at 37°C for 16 h, take a photo and perform colony counting.

[0221] Inoculate the Staphylococcus aureus strain into a test tube or bottle containing 10 mL of TSB using tryptic soy broth and incubate at 37°C for 24 hours. Using the McFarland standard, the target concentration is 1.0 (equivalent to approximately 1×10 8 CFU / mL). Dilute the pre-cultured bacterial solution to the McFarland 1.0 standard with sterile saline. Pour the prepared mannitol salt agar medium into a sterile petri dish, cool and solidify it. Use a sterile puncher to make a hole area on the agar plate. Prepare an antibacterial drug solution (DMSO) and perform a two-fold dilution series (initial concentration of 256 μg / mL, successively diluted to 128 μg / mL, 64 μg / mL, 32 μg / mL). Add 50 μL of antibacterial endoperoxide solutions with different concentrations (0, 32 μM, 64 μM, 128 μM) to each well, let it stand for a while to allow the drug solution to diffuse into the agar, and incubate the plate at 37°C for 24 hours. Observe the antibacterial effect of the drug according to the growth of Staphylococcus aureus. Set up a negative control group (without endoperoxide), and repeat the above experiment three times.

[0222] Inoculate the Candida albicans strain into a Sabouraud dextrose broth test tube (10 mL) and incubate at 37°C for 24 hours. Using the McFarland standard, the target concentration is 0.5 (1×10 6-1×10 7 (CFU / mL). The pre-cultured bacterial solution was diluted to McFarland 0.5 standard with sterile normal saline. The prepared Sabouraud dextrose agar was poured into a sterile petri dish and allowed to cool and solidify. A sterile cotton swab was used to evenly coat the plate with the Candida albicans bacterial solution of the pre-adjusted concentration. A hole-shaped area was made on the agar plate using a sterile punch. An antibacterial drug solution was prepared and subjected to a two-fold dilution series (initial concentration of 256 μg / mL, diluted successively to 128 μg / mL, 64 μg / mL, 32 μg / mL). 50 μL of the antibacterial endoperoxide solution at different concentrations (0, 32 μM, 64 μM, 128 μM) was added to each well. Let it stand for a moment to allow the drug solution to diffuse into the agar. The plate was incubated at 37 °C for 48 hours. The antibacterial effect of the drug was observed based on the growth of Candida albicans. A negative control group (without endoperoxide) was set, and the above experiment was repeated three times.

[0223] For other antifungal experiments, refer to the above procedure.

[0224] HSV-1 infection of Vero cells: Vero cells were placed in a 96-well plate and incubated in an incubator at 37 °C, 5% CO 2 for 2 hours to allow the virus to infect the cells, and then the virus solution was removed from the infected cells. Medium containing the drug (0, 10 μM, 20 μM - 100 μM) was added to each well, including a control group (without drug) and a positive control group (endoperoxide), and each treatment was set up in triplicate. The treated 96-well plate was returned to the incubator at 37 °C, 5% CO 2 and incubated for another 72 hours. The cell morphology was observed daily, the cytopathic effect was recorded, and finally the virus inhibition rate was calculated by the MTT method according to the following formula:

[0225]

[0226] For other antiviral experiments, refer to the above procedure.

[0227] Example 9: Psoriasis treatment experiment

[0228] Topical application of imiquimod cream was used to induce psoriasiform skin lesions in mice to establish a psoriasis model. After psoriasis induction, the mice were randomly divided into five groups and treated with endoperoxide ointment topically every day. At the same time point every day, an appropriate amount of the drug was evenly applied to the skin lesion area. The treatment continued for 21 days. The initial body weight and skin condition of each mouse were recorded. The changes in the skin lesions, including erythema, scale, and induration, were observed and recorded daily. The body weight of the mice was measured and recorded daily to monitor the effect of the drug on the overall health status.

[0229] Example 10: Acne regression test

[0230] Six patients with moderate acne were randomly divided into two groups, with 3 patients in the treatment group and 3 patients in the control group. After cleansing their faces in the morning and evening, each patient in the treatment group applied the gel prepared in Example 2 (Compound E11, content 5%) to the acne areas, while the control group did not receive any treatment. During the treatment process, the time for acne regression was photographed and recorded, and the curative effect was evaluated through the lesion regression rate. The recorded results are shown in Table 5.

[0231] Curative effect evaluation criteria: Cure: The lesion regression rate after treatment > 90%; Marked effect: The lesion regression rate is 60% - 90%; Effective: The lesion regression rate is 20% - 59%; Ineffective: It fails to meet the effective standard after treatment. The lesion regression rate = (the number of lesions before treatment - the number of lesions after treatment) / the number of lesions before treatment × 100%.

[0232] Safety indicators: Observe the occurrence of pigmentation and erythema in both groups, and evaluate the occurrence of pain in patients. Safe: No obvious pigmentation, erythema, and pain; Safety hazard: Appear mild pigmentation, erythema, and mild pain; Unsafe: Appear obvious pigmentation, erythema, and significant pain.

[0233] Example 11: Evaluation of the anti - microbial ability of internal - peroxide food preservatives

[0234] Thoroughly wash fresh strawberries with clean water to remove surface dirt and impurities. Rinse again with sterile distilled water to remove possible chemical residues. Gently dry the strawberries with sterile gauze or paper towels, avoiding damage to the epidermis. Use ethanol solutions of representative internal - peroxide E5 and aqueous solutions of E11 (concentrations 0.05%, 0.1%, 0.5%, 1%, 2%). Soak the pretreated strawberries in different concentrations of anti - microbial internal - peroxide solutions (ten in each group) for 5 minutes to ensure complete wetting of the strawberry surface. The control group was soaked in sterile distilled water. Dry the soaked strawberries in a sterile environment, avoiding direct sunlight. Place the treated strawberries at room temperature and observe the appearance changes of the strawberries every 3 days, including mildew, color change, and texture change. Record the decay situation and mold growth of the strawberries.

[0235] Table 1 Experimental results of the anti - Propionibacterium acnes of a series of compounds

[0236]

[0237] Note: H represents that the bacteriostatic rate of the compound > 80%, M represents that the bacteriostatic rate of the compound is between 80% - 50%, and L represents that the bacteriostatic rate of the compound < 50%. The bacteriostatic rate = (the number of bacteria in the control group - the number of surviving bacteria after administration) / the number of bacteria in the control group × 100%. BPO is benzoyl peroxide.

[0238] As can be seen from Table 1, the peroxides within the series have excellent inhibitory ability against Propionibacterium acnes. Among them, the substituents on the phenyl group affect the antibacterial effect to a certain extent. Among them, the endoperoxides with fatty carboxyl (or fatty acid ester) substituents on the phenyl group have excellent antibacterial efficacy. Taking compound E11 as an example, the singlet oxygen, pyridone benzoic acid, and triplet oxygen released by it act alone or synergistically to kill Propionibacterium acnes.

[0239] Table 2 Experimental results of the series of compounds against Escherichia coli

[0240]

[0241] Note: H represents that the antibacterial rate of the compound > 80%, M represents that the antibacterial rate of the compound is between 80% - 50%, and L represents that the antibacterial rate of the compound < 50%. Antibacterial rate = (number of bacteria in the control group - number of surviving bacteria after drug administration) / number of bacteria in the control group × 100%.

[0242] As can be seen from Table 2, the peroxides within the series have excellent inhibitory ability against Escherichia coli. Among them, the substituents on the phenyl group affect the antibacterial effect to a certain extent. Among them, the endoperoxides with good liposolubility have excellent antibacterial efficacy, and the results show that the endoperoxide molecule itself, the pyridone released by the endoperoxide, singlet oxygen, and triplet oxygen all have antibacterial efficacy against Escherichia coli.

[0243] Table 3 Experimental results of the series of compounds against Staphylococcus aureus

[0244]

[0245]

[0246] Note: The administration concentration of endoperoxide is 32 μM; H represents that the antibacterial rate of the compound > 80%, M represents that the antibacterial rate of the compound is between 80% - 50%, and L represents that the antibacterial rate of the compound < 50%. Antibacterial rate = (number of bacteria in the control group - number of surviving bacteria after drug administration) / number of bacteria in the control group × 100%. The concentration of endoperoxide in the Control group is 0 μM. ND indicates no inhibitory ability.

[0247] As can be seen from Table 3, the peroxides within the series have excellent inhibitory ability against Staphylococcus aureus. Among them, the substituents on the phenyl group affect the antibacterial effect to a certain extent. The results show that the endoperoxide molecule itself, the pyridone released by the endoperoxide, singlet oxygen, and triplet oxygen all have antibacterial efficacy.

[0248] Table 4 Experimental results of the series of compounds against Candida albicans

[0249]

[0250]

[0251] Note: The concentration of peroxy compound administered is 32 μM; H represents that the antibacterial rate of the compound > 80%, M represents that the antibacterial rate of the compound is between 80% - 50%, and L represents that the antibacterial rate of the compound < 50%. The antibacterial rate = (number of bacteria in the control group - number of surviving bacteria after administration) / number of bacteria in the control group × 100%. The concentration of peroxy compound in the Control group is 0 μM. ND indicates no inhibitory ability.

[0252] As can be seen from Table 4, the series of peroxy compounds have excellent inhibitory ability against Candida albicans. Among them, the substituents on the phenyl group affect the antibacterial effect to a certain extent. The results show that the peroxy molecule itself, the pyridone released by the peroxy group, singlet oxygen, and triplet oxygen all have antibacterial efficacy.

[0253] Table 5 Results of antiviral experiments on a series of compounds

[0254]

[0255] Note: The concentration of peroxy compound administered is 32 μM; H represents that the antibacterial rate of the compound > 80%, M represents that the antibacterial rate of the compound is between 80% - 50%, and L represents that the antibacterial rate of the compound < 50%. The antibacterial rate = (number of bacteria in the control group - number of surviving bacteria after administration) / number of bacteria in the control group × 100%. The concentration of peroxy compound in the Control group is 0 μM. ND indicates no inhibitory ability.

[0256] As can be seen from Table 5, the series of peroxy compounds have excellent inhibitory ability against HSV virus. The results show that the peroxy molecule itself, the pyridone released by the peroxy group, and singlet oxygen all have antiviral efficacy, and the molecule has good safety.

[0257] Table 6 Results of treating psoriasis with a series of compounds

[0258]

[0259]

[0260] Note: The dosage form used is (W / O) peroxy ointment; BSA score (Body Surface Area) is used to evaluate the percentage of the psoriasis lesion area in the total body surface area. By calculating the ratio of the area of the lesion area to the total surface area, the BSA score is obtained. The scoring range is from 0% (no lesion) to 100% (whole body lesion). H represents that the treatment ability of the compound > 80%, M represents that the treatment ability of the compound is between 80% - 50%, and L represents that the treatment ability of the compound < 50%.

[0261] As can be seen from Table 6, the series of peroxy compounds have good psoriasis treatment ability and safety.

[0262] Table 7 Evaluation of the curative effect of treating acne

[0263] Regression time (days) Patient 1 in the treatment group 6 Patient 2 in the treatment group 5 Patient 3 in the treatment group 7 Patient 1 in the control group >30 Patient 2 in the control group >30 Patient 3 in the control group >30

[0264] As can be seen from Table 7, the representative endoperoxide E11 gel can effectively kill Propionibacterium acnes and has the effects of keratolysis and exfoliation, and is expected to be developed into an effective drug for the treatment of acne. No obvious pigmentation, erythema or pain occurred during the treatment process, which proved that the series of compounds had excellent safety. Thus, it can be seen that the series of endoperoxides can be developed into effective drugs for the treatment of acne, with high efficacy and good safety. In addition, dosage forms such as gels and creams of the above-mentioned endoperoxides still showed excellent therapeutic effects and safety.

[0265] Table 8 Food Preservation Effect Evaluation

[0266]

[0267]

[0268] As can be seen from Table 8, both the representative endoperoxides E11 and E5 have excellent food preservation effects.

Claims

1. The compound of formula I or its pharmaceutically acceptable salt in the preparation of antibacterial drugs, antiviral drugs, food preservation and Application of disinfectant: in, R 1 , R 2 Each independently selected from C1-C10 alkyl, C1-C10 deuterated alkyl, -R1COOR, -COR3, -COOR, -R1COR3, -CONHR2, -R1CONHR2, nitro, trifluoromethyl, cyano, hydrogen, deuterium; R 3 -R 7 Each independently selected from hydrogen, C1-C10 alkyl, C1-C10 deuterated alkyl, C1-C10 fluoroalkyl, C1-C10 alkylamino, -OR2, -R1OR2, sulfonic acid, sulfonate, aminosulfonic acid, hydroxyl, amino, nitro, cyano, trifluoromethyl, halogen, -COOR, -R1COOR, -R1CONHR2, -R1COR3, -CONHR2, -COR3, -NHCOR3, n is an integer from 1 to 5000; R is independently a C1-C10 alkyl group, a C1-C10 deuterated alkyl group, H, a sodium ion, a potassium ion, a magnesium ion, a calcium ion, a zinc ion, an aluminum ion, an ammonium ion, or a tetraalkyl quaternary ammonium salt cation; R1 is independently C1-C10 alkylene or C1-C10 deuterated alkylene; R2 is independently C1-C10 alkyl, C1-C10 deuterated alkyl, or H; R3 is independently C1-C10 alkyl or C1-C10 deuterated alkyl; The alkyl groups in the tetraalkylammonium salt are each independently an alkyl group having 1 to 5 carbon atoms; R4 is independently a C1-C5 alkyl group, X - Selected from F - , Cl - Br - ,I - 、HSO4 - 、R5COO - ; R5 is each independently a C1-C10 alkylene group; R6 are each independently C1-C5 alkyl, C1-C5 alkoxy, or C2-C5 alkenyl; R7 is each independently a C1-C10 alkylene group.

2. The use according to claim 1, characterized in that: R 1 , R 2 Each independently selected from C1-C5 alkyl, C1-C5 deuterated alkyl, -COR3, -COOR, -R1COR3, -R1COOR, nitro, trifluoromethyl, cyano, hydrogen, deuterium; R 3 -R 7 Each independently selected from hydrogen, C1-C10 alkyl, C1-C10 deuterated alkyl, C1-C10 fluoroalkyl, -OR2, -R1OR2, sulfonic acid, sulfonate, aminosulfonic acid, hydroxyl, amino, nitro, cyano, trifluoromethyl, halogen, -COOR, -R1COOR, -R1CONHR2, -R1COR3, -CONHR2, -COR3, -NHCOR3, n is an integer from 1 to 1000; R is independently C1-C5 alkyl, C1-C5 deuterated alkyl, H + , sodium ion, potassium ion, magnesium ion, calcium ion, zinc ion, ammonium ion, tetraalkylammonium salt cation; R1 is independently C1-C5 alkylene or C1-C5 deuterated alkylene; R2 is independently C1-C5 alkyl, H; R3 is each independently a C1-C5 alkyl group; The alkyl groups in the tetraalkylammonium salt are each independently an alkyl group having 1 to 3 carbon atoms; R4 is independently a C1-C3 alkyl group, X - Selected from F - , Cl - Br - ,I - 、HSO4 - 、R5COO - ; R5 is each independently a C1-C8 alkylene group; R6 are each independently C1-C3 alkyl, C1-C3 alkoxy, or C2-C3 alkenyl; R7 is each independently a C1-C5 alkylene group.

3. The use according to claim 1, characterized in that: R 1 , R 2 Each is independently selected from methyl, trifluoromethyl, deuterated methyl, ethyl, deuterated ethyl, hydrogen, deuterium, -COOR, -COR3; R 3 -R 7 Each independently selected from hydrogen, C1-C5 alkyl, C1-C5 deuterated alkyl, C1-C5 fluoroalkyl, sulfonic acid, sulfonate, aminosulfonic acid, hydroxyl, amino, -OR2, -R1OR2, nitro, cyano, trifluoromethyl, halogen, -COOR, -NHCOR3, -R1COOR, -R1CONHR2, -R1COR3, -CONHR2, -COR3, n is an integer from 1 to 500; R is independently C1-C5 alkyl, H + , sodium ion, potassium ion, tetramethyl ammonium salt cation, tetraethyl ammonium salt cation; R1 is each independently a C1-C5 straight chain alkylene group; R2 is independently selected from methyl, ethyl, n-propyl, isopropyl, tert-butyl, n-butyl; R3 is each independently a C1-C5 alkyl group; R4 is independently a C1-C2 alkyl group, X - Selected from F - , Cl - Br - ,I - 、HSO4 - 、R5COO - ; R5 is each independently a C1-C5 alkylene group; R6 are each independently C1-C2 alkyl, C1-C2 alkoxy, or C2-C3 alkenyl; R7 is each independently a C1-C5 alkylene group.

4. The use according to claim 3, characterized in that: R 3 -R 7 Each is independently selected from hydrogen, methyl, deuterated methyl, ethyl, deuterated ethyl, propyl, deuterated propyl, trifluoromethyl, sulfonic acid, sulfonate, aminosulfonic acid, hydroxyl, amino, nitro, cyano, trifluoromethyl, halogen, -OR2, -R1OR2, -COOR, -NHCOR3, -R1COOR, -R1CONHR2, -R1COR3, -CONHR2, -COR3, n is an integer from 1 to 500; R is independently selected from methyl, ethyl, n-propyl, isopropyl, tert-butyl, sodium ion, potassium ion, magnesium ion, tetramethyl quaternary ammonium salt cation, tetraethyl quaternary ammonium salt cation; R1 is each independently a C1-C5 straight chain alkylene group; R2 is independently selected from methyl, ethyl, n-propyl, isopropyl, tert-butyl, n-butyl; R3 is each independently a C1-C5 alkyl group; R4 is methyl, X - Selected from F - , Cl - Br - ,I - 、HSO4 - HCOO - 、CH3COO - ; R5 is independently methylene, ethylene, propylene, butylene, or pentylene; R6 is independently methyl, ethyl, methoxy, ethoxy, or vinyl; R7 is independently methylene, ethylene, propylene, butylene or pentylene.

5. The use according to claim 1, characterized in that: The compound of formula I is selected from the following structures: X - Selected from F - , Cl - Br - ,I - 、HSO4-、HCOO - 、CH3COO - .

6. The use according to claim 1, characterized in that: The compound of formula I is selected from the following structures: X - Selected from F - , Cl - Br - ,I - 、HSO4-、HCOO - 、CH3COO - .

7. The use according to any one of claims 1 to 6, characterized in that: The dosage form of the drug is selected from one or more of gel, cream, solution, spray, aerosol, film, paste, tincture, spirit, lotion, ointment, powder, film coating, oil, plaster, powder, paste, pill, cake, lozenge, microemulsion, patch, cotton sheet, lotion.

8. The use according to any one of claims 1 to 6, characterized in that: Pharmaceutically acceptable salts of the compounds of Formula I include hydrochlorides, phosphates, sulfates, carbonates, bicarbonates, hexafluorophosphates, hydrobromides, hydrofluorides, nitrates, trimethylsulfonates, maleates, fumarates, methanesulfonates, sulfonates, citrates, tartrates, succinates, glutamates, and acetates.

9. The use according to any one of claims 1 to 6, characterized in that: The drug comprises: at least one of the compounds of formula I and a carrier; and / or pharmaceutical excipients; The carrier is selected from one or more of metal nanocarriers, non-metal nanocarriers, liposomes, microcapsule carriers that form a barrier between the drug and the skin, and matrix materials commonly used in preparing gels, ointments or creams; The pharmaceutical excipients are selected from one or more of diluents, adhesives, disintegrants, lubricants, glidants, flavoring agents, coating agents, gelatin capsule shells, latent solvents, propellants, surfactants, preservatives, lyophilization protectants, active agents, pH regulators, wetting agents, conditioners, antioxidants, solvents, fragrances, fillers, sunscreens, antibacterial agents, odor absorbers and pigments.

10. The use according to any one of claims 1 to 6, characterized in that: The drug comprises a compound of formula I or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable salt selected from metal nanocarriers, non-metal nanocarriers, liposomes, lactose, sucrose, chitosan, glucose, gelatin, glycerol, magnesium sulfate, magnesium stearate, sodium stearate, aluminum stearate, calcium stearate, stearic acid, butyl stearate, glyceryl stearate, sorbitol, mannitol, xylitol, cyclodextrin, β-cyclodextrin, maltitol, starch, gelatin, gum arabic, alginate, alginate, calcium phosphate, calcium carbonate, calcium bicarbonate, calcium silicate, cellulose, ethyl cellulose, Cellulose, methylcellulose, carboxymethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, cellulose acetate, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, mineral oil, propylene glycol, glycerine, butylene glycol, pentylene glycol, polyethylene glycol, vegetable oil, Witpso, Tween 61, cocoa butter, lauryl esters, guar gum, carob gum, xanthan gum, carbomer, polyacrylate, polyacrylamide, polyethylene, polyethylene, styrene, polypropylene, polystyrene, ethylene / acrylic acid copolymer, PTFE, silicone Alkane resin, polyvinyl alcohol, modified starch, collagen, gelatin, alkyl lactate, alkyl citrate, alkyl tartrate, sucrose ester, polyester, sorbitol ester, silicon derivative, agar, vaseline, paraffin, liquid paraffin, silicone oil, beeswax, lanolin, sodium fatty alcohol sulfate, polysorbate, cetyl octanoate, octyl isononanoate, myristyl lactate, cetyl lactate, isopropyl myristate, myristyl myristate, isopropyl palmitate, isopropyl adipate, decyl oleate, cholesterol isostearate, fatty alcohol, lauroyl lysine, phosphorus One or more of lipid materials, kaolin, talc, bismuth oxychloride, sericite, mica, zeolite, alumina, clay, kaolin, bentonite, hydrophobic silica, silicon dioxide, boron nitride, barium sulfate, vitamins, hexadecyl polyoxyethylene ethers, cetearyl polyoxyethylene ethers, stearyl polyoxyethylene ethers, PEG-stearate, decyl alcohol, cetyl alcohol, stearyl alcohol, lauryl alcohol, myristyl alcohol, oleyl alcohol, sodium lauryl sulfate, fatty acid soap, sodium lauryl polyoxyethylene ether sulfate, sodium hexadecyl polyoxyethylene ether phosphate and soybean lecithin.

11. The use according to any one of claims 1 to 6, characterized in that: The drug is a combination of a compound of formula I and a raw material for cosmetics or external medicines; The raw materials for cosmetics or quasi-medical products include at least one of a moisturizer, a thickener, a surfactant, an emulsion base, a preservative, an antioxidant, an alcohol, a fragrance, a pH adjuster, and a natural extract.

12. The use according to any one of claims 1 to 6, characterized in that: The medicine can be made into disinfectant, detergent, shower foam, ointment, wet tissue, lotion, washing soap, hand sanitizer, or added into shampoo, lotion, hair conditioner and skin care products for use.

13. The use according to any one of claims 1 to 6, characterized in that: The compound of formula I is used to prepare drugs for resisting Propionibacterium acnes, Escherichia coli, Staphylococcus aureus, Streptococcus, Burkholderia furunculosa, Pseudomonas aeruginosa, Clostridium difficile, Bacillus anthracis, Pseudomonas, Pseudomonas carrion, Candida albicans, dermatophytes, Candida, Aspergillus, mold, deep fungi, herpes virus, varicella-zoster virus, human papillomavirus, molluscum contagiosum virus, rubella virus, measles virus, and human immunodeficiency virus.

14. The use according to any one of claims 1 to 6, characterized in that: The skin diseases that the compounds of formula I are used to treat include acne, folliculitis, acne, pustules, papules, cysts, nodules, eczema, furuncle, flat warts, prickly heat, acne, erysipelas, fasciitis, rosacea, tinea capitis, tinea manuum and pedis, fungal dermatitis, tinea corporis and cruris, tinea versicolor, onychomycosis, pityriasis versicolor, hypertrophic scars, port wine stains, condyloma acuminatum, photoaging of the skin, psoriasis, erythematosus, herpes simplex, chickenpox, verrucous lesions, rubella, measles, hand, foot and mouth disease, skin diseases infected by HPV, and animal skin diseases caused by pathogenic microorganisms.

15. The use according to any one of claims 1 to 6, characterized in that: The compound of formula I is used for preparing medicines for treating oral infections, periodontitis, shoulder and other joint surgical infections, and pressure sore infections.

16. The use according to claim 13 or 14, characterized in that: The compounds of formula I are used alone or in combination with one or more other drugs.

17. The use according to claim 13 or 14, characterized in that: The compound of formula I is used for preparing medicines for combination with other oral, injectable and external medicines.

18. The use according to any one of claims 1 to 6, characterized in that: In the medicine, the content of the compound of formula I as an active substance is 0.01% to 50% by weight. Preferably, the content of the compound of formula I as active substance is 0.5% to 20% by weight. Preferably, in the drug, the content of the compound of formula I as an active substance is 1% to 15% by weight. More preferably, in the drug, the content of the compound of formula I as an active substance is 1% to 10% by weight.

19. An endoperoxide gel, characterized in that The components by weight are: The compound according to any one of claims 1 to 6: 0.1-10%; Purified water: 60-90%; Gel: 0-5%; Emollients: 0-5%; Humectant: 0-10%; Thickener: 0-3%; Preservatives: 0-1%; Antioxidants: 0-0.5%; Excipients: 0-5%; Stabilizer: 0-2%; pH adjuster: 0-1%; Fragrance: 0-1%; Pigment: 0-0.1%; The gel is selected from xanthan gum, carbopol, carbomer, sodium polyacrylate, hydroxypropyl methylcellulose, poloxamer 182, carbomer 940, docusate sodium, edetate disodium, silicon dioxide, polyvinyl alcohol, hydroxypropyl methylcellulose, sodium alginate, chitosan, gelatin, collagen, montmorillonite, polyurethane, and polyacrylamide; Emollients selected from mineral oil, vegetable oil, jojoba oil, avocado oil, glycerin, sodium lactate, glycerin, propylene glycol, polyethylene glycol, urea, hyaluronic acid, panthenol, lactic acid, glycyrrhizic acid, squalane, vegetable oil (such as coconut oil, almond oil, olive oil), honey extract, aloe extract; The moisturizer is selected from mineral oil, vegetable oil, jojoba oil, avocado oil, glycerin, sodium lactate, glycerin, propylene glycol, polyethylene glycol, urea, hyaluronic acid, panthenol, lactic acid, glycyrrhizic acid, squalane, vegetable oil (such as coconut oil, almond oil, olive oil), honey extract, aloe extract; The thickener is selected from xanthan gum, carboxymethyl cellulose, sodium carboxymethyl cellulose, methyl cellulose, sodium alginate, guar gum, acrylate copolymer, polyvinyl alcohol, polyacrylamide, gelatin, collagen, bentonite, silica gel, carbomer, hydroxypropyl methylcellulose; The preservative is selected from benzoic acid, sodium benzoate, parabens, methylparaben, propylparaben, ethylparaben, butylparaben, phenoxyethanol, benzyl alcohol, sorbic acid and its salts, benzalkonium chloride, ethanol, methylisothiazolinone, diimidazolidinyl urea, dihydroxytoluene dicarboxaldehyde, caprylyl glycol, chlorphenesin; The antioxidant is selected from vitamin E, tocopherol, ascorbic acid, sodium ascorbyl phosphate, butylated hydroxytoluene, butylated hydroxyanisole (BHA), coenzyme Q10, green tea extract, resveratrol, lipoic acid, grape seed extract, rosemary extract, alpha-tocopheryl acetate, and quercetin; The excipients are water, alcohol, glycerol, propylene glycol, polyethylene glycol, polyacrylamide, carbomer, hydroxypropyl methylcellulose, sodium alginate, xanthan gum, gelatin, chitosan, silicon dioxide, triglycerides, and dimethicone; The stabilizer is sodium EDTA, carbomer, xanthan gum, hydroxypropyl methylcellulose, sodium alginate, polyethylene glycol, gelatin, chitosan, silicon dioxide, sodium carboxymethyl cellulose, polyacrylamide, triethanolamine, sodium hydroxide, citric acid and its salts, EDTA and its salts; The pH adjuster is selected from triethanolamine, lactic acid, citric acid, acetic acid, phosphoric acid, sodium carbonate, sodium bicarbonate, sodium citrate, sodium lactate, sodium hydroxide, and potassium hydroxide.

20. An endoperoxide ointment, characterized in that: The components by weight are: The compound according to any one of claims 1 to 6: 0.5-22%; Matrix: 60-90%; Emollients: 0-5%; Thickener: 0-3%; Preservatives: 0-1%; Antioxidants: 0-0.5%; Excipients: 0-5%; Stabilizer: 0-2% Fragrance: 0-1%; Pigment: 0-0.1%; The matrix is ​​selected from vaseline, lanolin, vegetable oil, olive oil, almond oil, coconut oil, beeswax, polyethylene glycol, propylene glycol, glycerin, carbomer, stearyl alcohol, paraffin, glyceryl monostearate, sodium lauryl sulfate, glycerin, ethylparaben, Span-40, emulsifier OP, ethylparaben, stearic acid, white paraffin, liquid paraffin, white soft fat, beeswax, vegetable oil, glyceryl monostearate, polyethylene glycol, white vaseline, and higher alcohol; The emollient is selected from mineral oil, petrolatum, vegetable oil, lanolin, squalane, urea, amino acid, polyethylene glycol, beeswax, hyaluronic acid, plant extract (such as aloe extract, green tea extract), shea butter, jojoba oil, avocado oil, glycerin, sodium lactate; The thickener is selected from xanthan gum, gelatin, emulsifying wax, colloidal silicon, hydrogenated polyisobutylene, sodium carboxymethyl cellulose, carboxymethyl cellulose, polyvinyl alcohol, polyacrylamide, carbomer, hydroxypropyl methylcellulose, hydroxyethyl cellulose; The preservative is selected from sodium benzoate, parabens, methylparaben, ethylparaben, propylparaben, butylparaben, phenoxyethanol, benzyl alcohol, potassium sorbate, benzalkonium chloride, methylisothiazolinone, diimidazole urea, dihydroxytoluene dicarboxaldehyde, caprylyl glycol, chlorphenesin, and ammonium acetate; The antioxidant is selected from tocopherol, ascorbic acid, vitamin E, sodium ascorbyl phosphate, coenzyme Q10, resveratrol, green tea extract, lipoic acid, grape seed extract, rosemary extract, quercetin, β-carotene, tocopherol acetate; the excipient is xanthan gum, mineral oil, vaseline, lanolin, vegetable oil, shea butter, polyvinyl alcohol, emulsifying wax, alcohols, glycerin, propylene glycol, polyethylene glycol, polyacrylamide, carbomer, hydroxypropyl methylcellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, hydrogenated polyisobutylene, sodium alginate, xanthan gum, gelatin, chitosan, silicon dioxide, triglyceride, dimethyl silicone oil; The stabilizers are vitamin E, BHT, BHA, polysorbate, stearic acid, glyceryl monostearate, EDTA and its salts, citric acid and its salts, phosphates, liposomes, sodium lauryl sulfate, and polyethylene glycol.

21. An endoperoxygen cream, characterized in that: The components by weight are: The compound according to any one of claims 1 to 6: 0.5-10%; Matrix: 70-90%; Emollients: 0-30%; Thickener: 0-3%; Preservatives: 0-1%; Antioxidants: 0-0.5%; Excipients: 0-5%; Stabilizer: 0-2% Fragrance: 0-1%; Pigment: 0-0.1%; The matrix is ​​selected from water, urea, petrolatum, lanolin, mineral oil, vegetable oil, olive oil, almond oil, coconut oil, beeswax, polyethylene glycol, propylene glycol, glycerin, carbomer, stearyl alcohol, paraffin, stearic acid, triglyceride, glyceryl monostearate, sodium lauryl sulfate, glycerin, ethylparaben, Span-40, emulsifier OP, PEG-100 stearate, ethylparaben, stearic acid, white paraffin, liquid paraffin, white soft fat, beeswax, vegetable oil, glyceryl monostearate, carbomer, xanthan gum, hydroxypropyl methylcellulose, hydroxyethylcellulose, parabens, phenoxyethanol, potassium sorbate, polysorbates, monoglyceride stearate, cetearyl alcohol, polyethylene glycol, white petrolatum, and higher alcohol; The emollient is selected from mineral oil, petrolatum, olive oil, coconut oil, vegetable oil, shea butter, jojoba oil, almond oil, avocado oil, glycerin, sodium lactate, cetearyl alcohol, stearyl alcohol, triglyceride, caprylic / capric triglyceride, glyceryl monostearate, glyceryl stearate, propylene glycol, urea, aloe extract, oat extract, honey extract; The thickener is selected from xanthan gum, guar gum, gum arabic, carrageenan, carboxymethyl cellulose, carbomer, hydroxypropyl methylcellulose, hydroxyethyl cellulose, polyvinyl alcohol, methyl cellulose, cetearyl alcohol, stearyl alcohol, cetyl alcohol, emulsifying wax, bentonite, yellow wax, microcrystalline wax; The preservative is selected from sodium benzoate, phenoxyethanol, potassium sorbate, sodium benzoate, parabens, methylparaben, ethylparaben, propylparaben, butylparaben, methylisothiazolinone, methylchloroisothiazolinone, benzyl alcohol, caprylyl glycol, ethylhexylglycerin, diimidazoles urea, dihydroxydimethylhydantoin, chlorphenesin, triclocarban, grapefruit seed extract, tea tree oil; The antioxidant is selected from vitamin E, vitamin C, vitamin A, BHT, BHA, EDTA and its salts, tocopherol, ascorbic acid, green tea extract, grape seed extract, rosemary extract, coenzyme Q10, carotene, glutathione, resveratrol, catechins, citric acid, malic acid; The excipients are xanthan gum, mineral oil, vaseline, lanolin, vegetable oil, shea butter, polyvinyl alcohol, emulsifying wax, alcohols, glycerol, propylene glycol, polyethylene glycol, polyacrylamide, carbomer, hydroxypropyl methylcellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, hydrogenated polyisobutylene, sodium alginate, xanthan gum, gelatin, chitosan, silicon dioxide, triglyceride, and dimethyl silicone oil; The stabilizers are vitamin E, BHT, BHA, polysorbate, stearic acid, glyceryl monostearate, EDTA and its salts, citric acid and its salts, phosphates, liposomes, sodium lauryl sulfate, and polyethylene glycol.

22. An internal peroxygen disinfectant, characterized in that: The components by weight are: The compound according to any one of claims 1 to 6: 0.5-10%; Water: 86-99.4%; Stabilizer: 0.1%-1%; pH adjuster: 0%-0.5%; Preservatives: 0%-0.5%; Emulsifier: 0%-1%; Surfactant: 0%-0.1%; The stabilizer is citric acid and its salts, phosphates, acetic acid and its salts, ethylenediaminetetraacetic acid and its salts, citric acid, ascorbic acid, sodium thiosulfate, ethanol, isopropanol, glycerol, propylene glycol, polysorbate, phenoxyethanol, parabens, sodium bicarbonate, sodium chloride, etc. The pH adjuster is selected from triethanolamine, lactic acid, citric acid, acetic acid, phosphoric acid, sodium carbonate, sodium bicarbonate, sodium citrate, sodium lactate, sodium hydroxide, and potassium hydroxide. The preservatives are phenoxyethanol, parabens, potassium sorbate, and benzoate; The emulsifier is polysorbate 20, polysorbate 80, Span 60, Span 80, cetearyl alcohol, stearyl alcohol, polyoxyethylene fatty alcohol ether, Ceteareth-20, polyethers, phosphoric acid diester, cyclosiloxane, lecithin, polyethylene glycol; The surfactant is selected from polysorbate, cetyl alcohol polyether, sodium alkylbenzene sulfonate, quaternary ammonium salts, betaine, sodium lauryl sulfate, octylphenol polyoxyethylene ether, and phytosterol polyoxyethylene ether.

23. Compounds of the formula: X - Selected from F - , Cl - Br - ,I - 、HSO4-、HCOO - 、CH3COO - .

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