CN111437276A - A pharmaceutical composition for killing fungi or bacteria - Google Patents
A pharmaceutical composition for killing fungi or bacteria Download PDFInfo
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- CN111437276A CN111437276A CN202010214396.5A CN202010214396A CN111437276A CN 111437276 A CN111437276 A CN 111437276A CN 202010214396 A CN202010214396 A CN 202010214396A CN 111437276 A CN111437276 A CN 111437276A
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- pharmaceutical composition
- carvacrol
- thymol
- octenidine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
- A01N31/08—Oxygen or sulfur directly attached to an aromatic ring system
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
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- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Dentistry (AREA)
- Pest Control & Pesticides (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Plant Pathology (AREA)
- Environmental Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses a pharmaceutical composition for killing fungi or bacteria, which consists of octenidine and/or pharmacologically acceptable salts thereof and thymol and/or carvacrol.
Description
Technical Field
The invention relates to the field of medicines, in particular to a pharmaceutical composition for killing fungi or bacteria.
Background
With the progress of human civilization, the environmental sanitation is greatly improved, and some infectious diseases are effectively inhibited. However, the outbreak of infectious diseases, bird flu, SARS, MERS, COVID-19 and the like still do not happen, and the beriberi and onychomycosis still keep high outbreak. Therefore, there is a need to sterilize environmental commodity. However, most of the conventional disinfectants are synthetic disinfectants, such as benzalkonium chloride, chlorhexidine, polyhexamethylene biguanide and other quaternary ammonium salt disinfectants, or oxidizing agents, such as hydrogen peroxide, peracetic acid, sodium hypochlorite, ozone, chlorine and the like, or reducing agents, such as formaldehyde. These disinfectants or sterilizing agents are not ideal such as benzalkonium bromide, chlorhexidine, etc. Or a narrow range of applications, such as chlorhexidine or polyhexamethylene biguanide, can only be used at pH values in the range of 5 to 7. Or cause human and environmental hazards such as oxidizing and reducing agents.
Research and development of green disinfectants from natural sources has been the direction of industry effort. In ancient times, there have been descriptions of the use of plant essential oils as disinfecting preservatives and also for the treatment of bacterial infectious diseases such as peppermint, camphor, eucalyptus oil, lemon oil, thyme oil, oregano oil, etc., however, pure plant essential oils are mostly oil-soluble, have poor water solubility and are difficult to formulate disinfectant solutions with water, limiting their use. In addition, the sterilization effect of the plant essential oil is not ideal, and the plant essential oil is greatly influenced by the production area, the harvesting season and the extraction method.
Thymol (Thymol), the major component of essential oil of thyme (about 50%), is also present in essential oils of plants such as oregano and dried orange peel. Conventionally, it was determined that thymol has a minimum inhibitory concentration against Trichophyton rubrum and Candida albicans resistant to fluconazole of 64-128. mu.g/ml, and has a moderate antibacterial activity (Chinese agricultural report, 2009,25(01): 21-24).
Carvacrol (Carvacrol) is the main component of the essential oil of oregano, and the content is 70-80%. Chendeyu et al determined that carvacrol has a minimum inhibitory concentration of 25-200 μ g/ml against some fungi, and also belongs to a medium-strength antibacterial active compound (Luzhou institute of medicine, 1988,11(2): 106-7).
The water solubility of thymol and carvacrol is low, and solubilizers such as ethanol and propanol are required to be added when the solution is prepared. Some alcohol has a concentration of more than 50%. Alcohol is an organic solvent, is flammable, has a stimulating effect on wounds, increases COD (chemical oxygen demand) for the environment, and limits the use of thymol and carvacrol.
The invention unexpectedly finds that antibacterial agent Octenidine hydrochloride (Octenidine) and thymol or carvacrol have synergistic antibacterial effect, and the effect is better when the Octenidine hydrochloride, the thymol or the carvacrol are used together.
Disclosure of Invention
The invention aims to overcome the defects in the prior art and provides a pharmaceutical composition for killing fungi or bacteria.
In order to achieve the purpose, the invention adopts the technical scheme that:
the invention provides a pharmaceutical composition for killing fungi or bacteria, which consists of octenidine shown in structural formula I and/or pharmacologically acceptable salt thereof and a compound shown in structural formula II
Preferably, the pharmaceutically acceptable salt of octenidine is one or more of hydrochloride, hydrobromide, sulfate, phosphate, acetate, propionate, lactate, citrate, malate and gluconate.
Further preferably, the pharmaceutically acceptable salt of octenidine is hydrochloride.
Preferably, the octenidine hydrochloride content is higher than 95%.
Further preferably, the octenidine hydrochloride content is higher than 97%.
Most preferably, the content of octenidine hydrochloride is higher than 98.5 percent of the pure product.
Preferably, the compound of the structural formula II is thymol and/or carvacrol
Wherein the thymol can be obtained from natural sources, or extracted from plant essential oil, or exist in the plant essential oil, or can be obtained from chemical synthesis. The product may be pure or mixed. The pure product may be natural or synthetic. The content should be higher than 90%, preferably higher than 95%, most preferably higher than 98%. The mixture can only be derived from natural or natural extracts and should be present in an amount of more than 30%, preferably more than 40%, most preferably more than 50%.
Wherein the carvacrol can be from natural sources, or extracted from plant essential oil, or exists in the plant essential oil, or can be from chemical synthesis. The product may be pure or mixed. The pure product may be natural or synthetic. The content should be higher than 90%, preferably higher than 95%, most preferably higher than 98%. The mixture can only be derived from natural or natural extracts and should be present in an amount of more than 50%, preferably more than 60%, most preferably more than 70%.
Preferably, the weight ratio of the octenidine and/or the pharmacologically acceptable salt thereof to the compound of structural formula II is 1: 0.01-100.
Further preferably, the weight ratio of the octenidine and/or the pharmaceutically acceptable salt thereof to the compound of structural formula II is 1: 0.1-10.
Most preferably, the weight ratio of the octenidine and/or the pharmacologically acceptable salt thereof to the compound of structural formula II is 1: 0.2-5.
Preferably, the weight ratio of thymol to carvacrol is 1: 0.1-10.
Further preferably, the weight ratio of thymol to carvacrol is 1: 1-2.
Most preferably, the weight ratio of thymol to carvacrol is 1: 1.
Preferably, the weight ratio of the octenidine and/or a pharmacologically acceptable salt thereof to the thymol and the carvacrol is 1: 0.1-10.
Further preferably, the weight ratio of the octenidine and/or a pharmacologically acceptable salt thereof to the thymol and the carvacrol is 1: 0.2-5.
Most preferably, the weight ratio of the octenidine and/or a pharmacologically acceptable salt thereof to the thymol and the carvacrol is 1: 2.
Most preferably, the weight ratio of octenidine hydrochloride, thymol and carvacrol is 1:1: 1.
In a second aspect, the present invention provides a pharmaceutical composition preparation as described above, wherein the pharmaceutical composition is contained in the pharmaceutical composition preparation in an amount of 0.05% to 30% by weight.
Preferably, the weight percentage of the pharmaceutical composition is 0.1% -15%.
Most preferably, the weight percentage of the pharmaceutical composition is 0.1% -5%.
Preferably, one or more of a solvent, a solubilizer, a pH regulator, a pH buffer, a complexing agent, an antioxidant, a skin penetration enhancer, a humectant, a keratolytic agent, and a surfactant is further included.
Preferably, the pharmaceutical composition preparation is in the form of oil, cream, ointment, water, nail polish, mouthwash, spray or solid powder.
Further preferably, the formulation is an oil or aqueous formulation.
The solvent may be selected from water and/or organic solvent, preferably a mixed solvent of water and organic solvent, and the wound cleansing liquid and disinfectant liquid are mainly low-concentration alcohol water solvent, and the oil solvent is mainly used for directly applying on affected parts. The organic solvent is one or more of ethanol, n-propanol, isopropanol, n-butanol, 1, 2-propanediol, 1, 2-butanediol, 1, 2-hexanediol, oleyl alcohol, ethyl oleate, olive oil and soybean oil. Preferably one or more of ethanol, n-propanol, isopropanol, 1, 2-propanediol, 1, 2-butanediol, 1, 2-hexanediol, oleyl alcohol, ethyl oleate, olive oil and soybean oil.
The solubilizer is one or more of ethanol, n-propanol, isopropanol, n-butanol, 1, 2-propanediol, 1, 2-butanediol, 1, 2-hexanediol, and ethylhexyl glycerol ether, preferably ethanol, n-propanol, isopropanol, 1, 2-hexanediol, and ethylhexyl glycerol ether.
The pH value regulator is acid and/or alkali, preferably one or more of hydrochloric acid, acetic acid, citric acid and sodium hydroxide.
The pH buffer is one or more of a phosphate buffer, an acetate buffer, a citrate buffer and a borate buffer, preferably a phosphate buffer and/or a citrate buffer.
The complexing agent is one or more of citric acid and salts thereof, polyphosphoric acid and salts thereof, ethylene diamine tetraacetic acid and salts thereof, nitrilotriacetic acid and salts thereof, and citric acid and salts thereof and/or ethylene diamine tetraacetic acid and salts thereof are preferred.
The surfactant is one or more of cationic surfactant, anionic surfactant and nonionic surfactant, preferably nonionic surfactant.
Antioxidant, skin penetration enhancer, humectant, cutin softener, etc. can be added according to the requirement.
In a third aspect, the invention provides a pharmaceutical composition preparation as described above for use in surgical instrument disinfection, household environment disinfection, wound cleaning disinfection or prevention and treatment of superficial fungal infection.
Preferably, the pharmaceutical composition is formulated as a 0.1-1.5% strength aqueous or low alcohol aqueous solution preparation for use as a surgical instrument cleaning solution, a wound cleaning disinfectant solution, or a cleaning solution for denture contact lenses.
Preferably, the pharmaceutical composition is prepared into a concentrated solution preparation with the concentration of 1.5-15%, and is added into foot soaking water to kill fungi and prevent and treat tinea pedis; or adding into bath lotion, cleaning vagina, and treating and preventing gynecological inflammation, especially gynecological inflammation caused by bacteria and mold.
Preferably, the pharmaceutical composition is formulated into 0.1-1.5% mouth wash for eliminating halitosis, and preventing and treating one or more of stomatitis, pharyngolaryngitis, gingivitis and periodontitis.
Preferably, the pharmaceutical composition is formulated into oil, cream, ointment, nail polish with a concentration of 0.5-15% for direct application to the affected part for preventing and treating beriberi and/or onychomycosis.
Preferably, the pharmaceutical composition is formulated as a spray for disinfection and mite control of one or more of shoes, socks, mattresses, sofa cushions and car seats.
By adopting the technical scheme, compared with the prior art, the invention has the following technical effects:
the invention greatly improves the antibacterial effect of the thymol and/or the carvacrol, reduces the effective antibacterial concentration of the two compounds, increases the solubility of the bailidol and the carvacrol in water, reduces the alcohol amount for preparing the thymol and carvacrol solution, reduces the irritation of the thymol and the carvacrol, and enlarges the application range of the thymol and the carvacrol.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
It should be noted that the embodiments and features of the embodiments may be combined with each other without conflict.
The following specific examples further illustrate the invention but are not to be construed as limiting the invention.
Example 1
1 preparation of sample solution
THY (thymol) 200. mu.g/ml solution
Dissolving thymol 20mg in water and small amount of Tween-80, diluting to 100ml, and shaking to obtain 200 μ g/ml thymol solution.
CAR (carvacrol) 200. mu.g/ml solution
Dissolving carvacrol 20mg in water and small amount of Tween-80, diluting to 100ml, and shaking to obtain carvacrol solution of 200 μ g/ml.
OCT (octenidine hydrochloride) 200. mu.g/ml solution.
20mg of octenidine hydrochloride is dissolved by water and a small amount of Tween-80, diluted to 100ml and shaken up to obtain the octenidine hydrochloride solution with 200 mug/ml.
THY + OCT solution
Mixing 25ml of THY 200 μ g/ml solution and 25ml of OCT 200 μ g/ml solution, diluting with water and small amount of Tween-80 to 100ml, and shaking.
CAR + OCT solution
And (3) taking 25ml of CAR 200 mu g/ml solution and 25ml of OCT 200 mu g/ml solution, mixing, diluting to 100ml with water and a small amount of Tween-80, and shaking up to obtain the final product.
THY + CAR + OCT solution
Taking 25ml of THY 200 mu g/ml solution, 25ml of CAR 200 mu g/ml solution and 25ml of OCT 200 mu g/ml solution, mixing, diluting with water and a small amount of Tween-80 to 100ml, and shaking up.
2 bacteriostatic test
Streaking test strains into corresponding test tube slant culture medium, culturing bacteria in 37 deg.C constant temperature incubator for 24 hr, culturing fungi in 28 deg.C constant temperature incubator for 5d, and refrigerating in 4 deg.C refrigerator for use.
Preparation of test strain suspension: respectively picking a small amount of bacteria or fungal spores by using an inoculating loop, oscillating in a triangular flask filled with glass beads and 10ml of sterile normal saline, and measuring the number of bacteria by adopting a viable count method to prepare uniform bacteria suspension or spore suspension with the concentration of the bacteria or spores of 106-107 CFU/ml.
Placing sterilized and dried Oxford cups (8 mm in outer diameter, 6mm in inner diameter and 10mm in height) into a culture dish which is uniformly coated with 0.1ml of bacterial suspension, respectively injecting 200 mu L blank reference solutions into the Oxford cups by using a sterile micropipette, and enabling each bacterium to be parallel to each other, carrying out constant-temperature culture on the bacteria for 24 hours, carrying out culture on the fungi for 5 days, measuring the diameter of a bacteriostatic circle, and calculating the bacteriostatic rate, wherein the results are shown in the following table:
TABLE 1 results of the bacteriostatic test
As can be seen from the above table, no matter whether the bacteria or the fungi exist, the THY 50 mug/ml + OCT 50 mug/ml, CAR 50 mug/ml + OCT 50 mug/ml, THY 50 mug/ml + CAR 50 mug/ml + OCT 50 mug/ml all reach or exceed the bacteriostasis rate of THY, CAR, OCT 200 mug/ml, which indicates that the octenidine hydrochloride has synergistic and superposed bacteriostasis to thymol and carvacrol.
Example 2
1. Disinfectant fluid
The disinfectant fluid is used for cleaning wounds or disinfecting directly, and the formula of the disinfectant fluid is shown in table 2.
TABLE 2
| Name of material | F1 | F2 | F3 | F4 |
| Thymol | 0.05％ | - | 0.05％ | 0.05％ |
| Carvacrol | - | 0.05％ | 0.05％ | 0.05％ |
| Octenidine hydrochloride | 0.05％ | 0.05％ | 0.05％ | 0.10％ |
| 3% of n-propanol | 99.90％ | 99.90％ | 99.85％ | 99.80％ |
2. Concentrated water
The concentrated water is diluted according to a certain proportion, is used for cleaning wounds or sterilizing, and can be directly added into foot washing water and bathing water, and the formula is shown in table 3.
TABLE 3
| Name of material | F5 | F6 |
| Thymol | 1.0％ | 2.0％ |
| Carvacrol | 1.0％ | 1.0％ |
| Octenidine hydrochloride | 1.0％ | 1.0％ |
| 30% isopropyl alcohol | 97％ | - |
| 75% ethanol | - | 96.0％ |
3. Oil preparation
Directly applied to affected parts such as tinea pedis, onychomycosis, etc., and its formula is shown in Table 4.
TABLE 4
| Name of material | F7 | F8 |
| Thymol | 1.0％ | 2％ |
| Carvacrol | 1.0％ | 2％ |
| Octenidine hydrochloride | 1.0％ | 1％ |
| Oleyl alcohol | 97％ | 95％ |
Alternatively, the oils can be formulated directly with essential oils, the formulation of which is shown in Table 5.
TABLE 5
4. Nail polish
The formulation is shown in table 6.
TABLE 6
| Name of material | F11 | F12 |
| Thyme oil | 0.25％ | 0.25％ |
| Oregano oil | 0.25％ | 0.25％ |
| Octenidine hydrochloride | 0.5％ | 0.25％ |
| Hydroxypropyl chitosan | 1.00％ | 0.75％ |
| 70% ethanol | 98.00％ | 98.50％ |
While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention.
Claims (9)
1. A pharmaceutical composition for killing fungi or bacteria is characterized by comprising octenidine shown in structural formula I and/or pharmacologically acceptable salt thereof and a compound shown in structural formula II
2. The pharmaceutical composition according to claim 1, wherein the pharmaceutically acceptable salt of octenidine is one or more of hydrochloride, hydrobromide, sulfate, phosphate, acetate, propionate, lactate, citrate, malate and gluconate.
3. The pharmaceutical composition of claim 1, wherein the compound of formula II is thymol and/or carvacrol
4. The pharmaceutical composition according to claim 1, wherein the weight ratio of octenidine and/or its pharmacologically acceptable salt to the compound of structural formula II is 1: 0.01-100.
5. A pharmaceutical composition according to claim 3, wherein the weight ratio of thymol to carvacrol is from 1:0.1 to 10.
6. A pharmaceutical composition formulation according to any one of claims 1 to 5, wherein the weight percentage of the pharmaceutical composition in the pharmaceutical composition formulation is between 0.05% and 30%.
7. The pharmaceutical composition formulation of claim 6, further comprising one or more of a solvent, a solubilizer, a pH adjuster, a pH buffer, a complexing agent, an antioxidant, a skin penetration enhancer, a humectant, a keratolytic agent, and a surfactant.
8. The pharmaceutical composition preparation according to claim 6, wherein the pharmaceutical composition preparation is in the form of oil, cream, ointment, water, nail polish, mouthwash, spray or solid powder.
9. Use of a pharmaceutical composition according to any one of claims 6 to 8 for the preparation of a medicament for the disinfection of surgical instruments, domestic environments, wound cleansing and disinfection or for the prevention and treatment of superficial fungal infections.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| KR102217617B1 (en) * | 2020-08-14 | 2021-02-19 | 비엘엔에이치 주식회사 | Pharmaceutical composition for preventing or treating tinea |
| CN113082029A (en) * | 2021-03-02 | 2021-07-09 | 浙大宁波理工学院 | Wound cleaning disinfectant |
| WO2022035031A1 (en) * | 2020-08-14 | 2022-02-17 | 비엘엔에이치 주식회사 | Pharmaceutical composition for prevention or treatment of tinea |
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| US20130156708A1 (en) * | 2011-12-20 | 2013-06-20 | Symrise Ag | Phenol derivatives as antimicrobial agents |
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| US20130156708A1 (en) * | 2011-12-20 | 2013-06-20 | Symrise Ag | Phenol derivatives as antimicrobial agents |
| CN106413404A (en) * | 2014-04-25 | 2017-02-15 | 弗莱克西格专利有限责任公司 | Improved biocide compositions based on calcium fluoride as well as uses thereof |
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| Title |
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| MOHAMMAD Y. MEMAR等: "Carvacrol and thymol; Strong antimicrobial agents against resistant isolates", 《REVIEWS IN MEDICAL MICROBIOLOGY》 * |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102217617B1 (en) * | 2020-08-14 | 2021-02-19 | 비엘엔에이치 주식회사 | Pharmaceutical composition for preventing or treating tinea |
| WO2022035031A1 (en) * | 2020-08-14 | 2022-02-17 | 비엘엔에이치 주식회사 | Pharmaceutical composition for prevention or treatment of tinea |
| JP2022547755A (en) * | 2020-08-14 | 2022-11-16 | ビーエルアンドエイチ カンパニー，リミテッド | Pharmaceutical composition for preventing or treating ringworm |
| CN113082029A (en) * | 2021-03-02 | 2021-07-09 | 浙大宁波理工学院 | Wound cleaning disinfectant |
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