CN116059271A - Combined antibacterial medicine, preparation method thereof and skin dressing using same - Google Patents

Combined antibacterial medicine, preparation method thereof and skin dressing using same Download PDF

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Publication number
CN116059271A
CN116059271A CN202310047727.4A CN202310047727A CN116059271A CN 116059271 A CN116059271 A CN 116059271A CN 202310047727 A CN202310047727 A CN 202310047727A CN 116059271 A CN116059271 A CN 116059271A
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mixed
vitamin
silver
patch
mixed component
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刘贞君
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Qingdao No5th People's Hospital
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Qingdao No5th People's Hospital
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/24Heavy metals; Compounds thereof
    • A61K33/38Silver; Compounds thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/045Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365Lactones
    • A61K31/375Ascorbic acid, i.e. vitamin C; Salts thereof
    • AHUMAN NECESSITIES
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/28Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/282Artemisia, e.g. wormwood or sagebrush
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    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/53Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/534Mentha (mint)
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    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/18Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing inorganic materials
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    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
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    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
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    • A61L15/40Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing ingredients of undetermined constitution or reaction products thereof, e.g. plant or animal extracts
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    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
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    • A61L15/42Use of materials characterised by their function or physical properties
    • A61L15/46Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
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    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/102Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
    • A61L2300/104Silver, e.g. silver sulfadiazine
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    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/216Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
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    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404Biocides, antimicrobial agents, antiseptic agents
    • AHUMAN NECESSITIES
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    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
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    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412Tissue-regenerating or healing or proliferative agents
    • AHUMAN NECESSITIES
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    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/428Vitamins, e.g. tocopherol, riboflavin
    • AHUMAN NECESSITIES
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    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/45Mixtures of two or more drugs, e.g. synergistic mixtures
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    • A61L2400/12Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
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    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
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    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

A combined antibacterial medicine for skin wound dressing, preferably made into patch, comprises effective raw materials and medicinal carrier, wherein the effective raw materials comprise silver nitrate, herba Menthae-folium Artemisiae Argyi mixed extract, and vitamin C in a proportion such that the molar ratio of silver ion, menthol, and vitamin C is 1:3.5-6:0.3-0.7. Mixing all silver nitrate with 20-60% of total amount of herba Menthae-folium Artemisiae Argyi mixed extract to obtain first mixed component; mixing vitamin C with the rest herba Menthae-folium Artemisiae Argyi mixed extract to obtain second mixed component; split charging and mixing at the time of use. The comprehensive antibacterial, anti-inflammatory and healing-promoting effects of the medicine are fully exerted by controlling the raw material dosage, the vitamin C and silver ions are split-packed, so that a large amount of silver ions are prevented from being converted into nano silver, the total dosage of natural biological components of peppermint and wormwood is not reduced, the natural biological components are added in two parts, the excessive biological reduction effect on the silver ions is avoided, a certain amount of tiny nano silver simple substance can be induced to generate, and the sterilization effect is enhanced.

Description

Combined antibacterial medicine, preparation method thereof and skin dressing using same
Technical Field
The invention relates to the technical field of medical antibacterial dressings, in particular to a combined antibacterial drug, a preparation method thereof and a skin dressing using the same.
Background
The mixed extract of peppermint and wormwood can be used for preparing a green natural antibacterial pharmaceutical preparation, particularly, the mixed extract of peppermint and wormwood is combined with a traditional silver ion antibacterial liquid preparation to prepare a mint-wormwood biological extract containing silver ions, and then vitamin C with specific effects of preventing infection and promoting wound healing is added, so that the combined antibacterial, anti-inflammatory and healing-promoting effects can be obtained, and the mixed extract can be applied to wound anti-infection, sterilization and care.
Although the mint-wormwood biological extract contains various components, the main effective components such as menthol derived from the mint extract are proved to be effective in enhancing the antibacterial activity of silver ions, and studies have shown that the antibacterial activity effect of the compound administration of silver ions and menthol exceeds the antibacterial activity effect of the individual administration and accumulation of the two. However, the existing silver nitrate/mint-mugwort extract/vitamin C combined antibacterial drug still shows a certain instability of antibacterial activity in experiments, and is mainly characterized in that the dynamic change of silver ions and particle content is mainly realized, because the mint-mugwort mixed extract contains some ketone, ester and aromatic substances besides menthol, the whole product shows a certain biological reduction effect on silver ions, and vitamin C is a component with a very high reduction effect on silver ions, so that the content of the mint-mugwort mixed extract and vitamin C in the antibacterial drug reaches a certain degree, the conversion of silver ions to silver crystal particles is promoted, aggregation and precipitation are easy to generate, the drug property function is influenced and changed, and the storage life of the drug is reduced.
Disclosure of Invention
In order to solve the problems still existing in the prior art, the invention provides a combined antibacterial medicament which takes silver nitrate, mint-wormwood mixed extract and vitamin C as active ingredients, and the antibacterial activity is further stabilized on the basis of ensuring the dosage of natural biological ingredients by proportioning and split charging mixing of the active ingredients, so that the comprehensive antibacterial, anti-inflammatory and healing-promoting effects are achieved.
The aim of the invention is achieved by the following technical scheme.
The combined antibacterial drug comprises effective raw materials and a drug carrier, wherein the effective raw materials comprise silver nitrate, a mint-wormwood mixed extract and vitamin C according to a certain proportion, and the proportion of the silver nitrate, the mint-wormwood mixed extract and the vitamin C is that the molar proportion of silver ions, menthol and vitamin C is 1:3.5-6:0.3-0.7.
Preferably, the molar concentration of silver ions in the combined antibacterial agent is 0.4-1.0mM.
Preferably, the above combined antibacterial agent contains no other effective raw materials except for the silver nitrate, the mint-wormwood mixed extract and the vitamin C.
Preferably, the drug carrier in the combined antibacterial drug is a high water seepage solution.
A method for preparing the above combined antibacterial agent comprises mixing silver nitrate and herba Menthae-folium Artemisiae Argyi mixed extract 20-60% of the total amount to obtain first mixed component; mixing vitamin C with the rest herba Menthae-folium Artemisiae Argyi mixed extract to obtain second mixed component; the first mixed component and the second mixed component are dispensed and mixed at the time of use.
Preferably, in the preparation method of the combined antibacterial drug, the first mixed component and the second mixed component are liquid.
A skin dressing is prepared from the above antibacterial composition.
Preferably, the skin dressing is made into a patch.
Preferably, the patch manufactured by the skin dressing is divided into a main patch and a sub patch, wherein the main patch is manufactured by using a first mixed component, the sub patch is manufactured by using a second mixed component, or the sub patch is manufactured by using the first mixed component, and the main patch is manufactured by using the second mixed component.
Preferably, the main patch and the sub patches in the patch manufactured by the skin dressing are packaged separately.
The beneficial effects of the invention are as follows:
the invention provides a combined antibacterial drug which comprises effective raw materials and a drug carrier, wherein the effective raw materials and the drug carrier consist of silver nitrate, a mint-wormwood mixed extract and vitamin C according to a certain proportion, and the molar ratio of silver ions, menthol and vitamin C components is 1 by controlling the use amount of the raw materials: 3.5-6:0.3-0.7, fully exerting the comprehensive antibacterial, anti-inflammatory and healing-promoting effects of the medicine, wherein the molar concentration of silver ions is in the range of 0.4-1.0mM, and the molar ratio of silver ions to menthol is 1:3.5-6, and the killing effect on common strains is greatly improved under the condition of the existence of vitamin C.
The molar ratio of silver ions to vitamin C components of the combined antibacterial drug provided by the invention is controlled to be 1:0.3-0.7, and split charging vitamin C with high reducibility and silver ions, thereby avoiding the conversion of a large amount of silver ions into nano silver.
According to the combined antibacterial drug, the mint-wormwood mixed extract is added into two parts according to the dynamic control requirement of silver ions on the basis of improving the dosage of natural biological components, so that excessive biological reduction effect of the mint-wormwood mixed extract on the silver ions is avoided, a certain amount of tiny and uniform nano silver can be generated after the drug is prepared into a patch (before use) according to the requirement, the biological reduction effect is a weak effect, the reaction is controllable, the generated nano silver particles are tiny and are not easy to agglomerate and precipitate, the extract after the reaction is also capable of protecting and dispersing the generated nano silver, not only can stabilizing the silver ions, but also can stabilize the tiny nano silver particles, and although the silver ions have more direct sterilizing effect, the nano silver has more outstanding sterilizing effect than the silver ions, namely, the tiny silver ions are easier to penetrate through the surface layer of bacteria to enter cells so as to cells when the tiny nano silver ions exist in a simple substance state, and therefore, the generation of a certain amount of simple substance can be guided to cooperate with silver to double sterilizing effect.
Drawings
Fig. 1 is a schematic diagram of skin auxiliary material composition according to an embodiment of the present invention.
The reference numerals in the drawings are:
1. main plaster, 2, sub plaster.
Detailed Description
Exemplary embodiments of the present disclosure will be described in more detail below with reference to the accompanying drawings. It should be noted that these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosure to those skilled in the art, and the disclosure may be embodied in various forms and should not be limited by the embodiments set forth herein.
Example 1
A combined antibacterial drug comprises effective raw materials and hypertonic aqueous solution which are composed of silver nitrate, mint-wormwood mixed extract and vitamin C according to a certain proportion, wherein the molar concentration of silver ions in the combined antibacterial drug is controlled to be 0.4-1.0mM, preferably 0.5-0.8mM by controlling the dosage of the silver nitrate, and the molar ratio of silver ions, menthol and vitamin C is controlled to be 1 by controlling the proportion of the silver nitrate, the mint-wormwood mixed extract and the vitamin C: 3.5-6:0.3-0.7, preferably 1:4-6:0.4-0.6. In order to simplify experimental conditions, the combined antibacterial drug of the embodiment does not contain other effective raw materials except the silver nitrate, the mint-wormwood mixed extract and the vitamin C. The mass ratio of the herba Menthae-folium Artemisiae Argyi extract should be controlled to be not more than 50%, preferably 20% -30%, and the menthol content can be estimated or measured according to the amount of herba Menthae extract.
The molar ratio of the silver ions, menthol and vitamin C components is controlled by controlling the raw material dosage, so that the comprehensive antibacterial, anti-inflammatory and healing-promoting effects of the medicine are fully exerted, and the molar concentration of the silver ions is 0.4-1.0mM range and silver ion to menthol molar ratio is in the range of 1:3.5-6, and can play a good role in killing common strains of skin wounds in the presence of vitamin C. Taking the example of the concentration of silver ions in the glycerol high-permeability water solution of 0.65mM on the basis, the molar ratio of the silver ions, menthol and vitamin C components is controlled to be 1:6:0.5, using an as-prepared solution (used within 30min after stirring) using a general validation method for incubation with E.coli cell suspensions, log 10 CFU/mL shows that compared with pure silver nitrate solution, the method can lead the activity of bacteria to be eliminated to the initial time of incubation, and the method adopts staphylococcus aureus and other strains for verification, and is also superior to the effect of singly adopting silver ions.
Example 2
This example provides a method for preparing a combination antibacterial agent, taking the combination antibacterial agent of preparation example 1 as an example, mixing 45% of the total amount of all the silver nitrate and the mixed extract of peppermint-mugwort in a highly water-permeable solution to prepare a first mixed component, mixing vitamin C and the remaining mixed extract of peppermint-mugwort in a highly water-permeable solution to prepare a second mixed component, and packaging the first mixed component and the second mixed component (mixing while leaving for use).
The molar ratio of silver ions to vitamin C components is controlled to be 1:0.3-0.7, and split charging vitamin C with high reducibility and silver ions, avoiding the conversion of a large amount of silver ions to nano silver, simultaneously, on the basis of improving the natural biological component dosage by using the mint-wormwood mixed extract, according to the dynamic control requirement of the silver ions, the mint-wormwood mixed extract is divided into two parts to be added, and only one part of the mint-wormwood mixed extract is mixed with the silver ions in advance, thereby avoiding the excessive biological reduction effect of the mint-wormwood mixed extract on the silver ions, ensuring that a certain amount of tiny and uniform nano silver is generated after the medicament is prepared into a patch (before use) according to the requirement, ensuring that the medicament is prepared into a small amount of nano silver as required, ensuring that the biological reduction effect is a weak effect, ensuring that the generated nano silver particles are tiny and are not easy to agglomerate and precipitate, ensuring that the extract after the reaction is finished has the protection and dispersion effect on the generated nano silver particles, and stabilizing the tiny nano silver particles, and although the silver ions have more direct sterilization effect, the nano silver has more outstanding effect than the silver ions, on the silver ions are easy to enter into cells in a penetrating state when the nano silver ions exist, thus the silver ions are more quantitatively matched with the silver cells to realize the dual sterilization effect.
To verify this effect, the molar ratio of silver ion, menthol, vitamin C components was still 1:6:0.5, and designing a comparison experiment, wherein the first mixed component (marked as sample 1) prepared above is subjected to a stability experiment for 60 days, the solution adopted in the comparison experiment is a mixed component (marked as sample 2) prepared by mixing silver nitrate, a mint-wormwood mixed extract and vitamin C completely, the silver nitrate content of the mixed component is the same as that of sample 1, the sample 1 and the sample 2 are stored at constant temperature and in a dark place by using an equal-volume measuring flask, the silver ion concentration is recorded before and after the experiment, the silver ion concentration reduction ratio is calculated after the experiment is finished, the silver ion concentration reduction ratio of the sample 1 is controlled to be about 9.7%, the silver ion concentration reduction ratio of the sample 2 reaches 47.9%, nearly half of silver ions are reduced, and the precipitate is separated and detected, so that the generation of nano silver can be detected. The content of silver ions and nano silver particles can be dynamically adjusted by adjusting the dosage of the mint-wormwood mixed extract mixed with silver nitrate, and the nano silver particles and the ion simple substance ratio with ideal granularity and distribution can be obtained under the condition that 20-60%, more preferably 30-50% of the total dosage of the whole silver nitrate and the mint-wormwood mixed extract is preferably mixed as a first mixed component, so that the enhanced sterilization effect is obtained.
Example 3
The main purpose of the invention is to provide a skin wound dressing with comprehensive antibacterial, anti-inflammatory and healing promoting effects, so the embodiment provides the application.
As shown in fig. 1, a patch was prepared using the combined antibacterial agent prepared in example 2, and the patch was divided into a main patch 1 and a sub patch 2, wherein the main patch 1 was prepared using a first mixed component, the sub patch 2 was prepared using a second mixed component, and the sub patch 2 was prepared using the first mixed component, and the main patch 1 was prepared using the second mixed component. In order to achieve the above-mentioned effect of separately packaging the first mixed component and the second mixed component, the main patch 1 and the sub-patch 2 in the patch should be separately packaged, for example, they may be packaged separately and then put into a total package, or may be separated in a package by using a separate interlayer, and when in use, the sub-patch 2 is directly attached to the main patch 1 to complete the mixing of all the active components.
The patch of this embodiment is exemplified by that if the main patch 1 and the sub patch 2 are changed into the impregnating solution to infiltrate the medical cotton cloth or the non-woven fabric, etc., the first mixed component and the second mixed component can be made into a liquid isolation package for cooperation, and the influence of time factors on the drug properties can be eliminated theoretically in any split charging method, so that the quality guarantee period of the manufactured medical product is also more flexible.
The present invention is not limited to the above-mentioned embodiments, and any changes or modifications within the scope of the present invention will be apparent to those skilled in the art. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.

Claims (10)

1. The combined antibacterial drug is characterized by comprising effective raw materials and a drug carrier, wherein the effective raw materials comprise silver nitrate, a mint-wormwood mixed extract and vitamin C according to a certain proportion, and the proportion of the silver nitrate, the mint-wormwood mixed extract and the vitamin C is that the molar proportion of silver ions, menthol and vitamin C is 1:3.5-6:0.3-0.7.
2. A combination according to claim 1, wherein the molar concentration of silver ions in the combination is 0.4-1.0mM.
3. A combination antibacterial agent according to claim 1, wherein the active ingredients are absent except for the silver nitrate, the mint-mugwort mixed extract, and vitamin C.
4. A combination antibacterial agent according to claim 1, wherein the pharmaceutical carrier is a highly aqueous solution.
5. A method of preparing a combination antibacterial agent according to claim 1, characterized in that the total amount of silver nitrate and the total amount of the mint-mugwort mixed extract is mixed to form a first mixed component; mixing vitamin C with the rest herba Menthae-folium Artemisiae Argyi mixed extract to obtain second mixed component; the first mixed component and the second mixed component are dispensed and mixed at the time of use.
6. The method of claim 5, wherein the first and second mixed components are liquids.
7. A skin dressing characterized by using the combination antibacterial agent prepared by the method for preparing a combination antibacterial agent according to claim 5 or 6.
8. The skin dressing of claim 7, wherein the skin dressing is fabricated as a patch.
9. The skin dressing of claim 8, wherein the patches are divided into a main patch and a sub patch, the main patch being made using a first mixed component and the sub patch being made using a second mixed component, or the sub patch being made using the first mixed component and the main patch being made using the second mixed component.
10. The skin dressing of claim 9, wherein the main patch and the sub-patches are packaged separately.
CN202310047727.4A 2023-01-31 2023-01-31 Combined antibacterial medicine, preparation method thereof and skin dressing using same Pending CN116059271A (en)

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104274490A (en) * 2009-02-11 2015-01-14 雷蒙特亚特特拉维夫大学有限公司 Antiseptic compositions comprising silver ions and menthol and uses thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104274490A (en) * 2009-02-11 2015-01-14 雷蒙特亚特特拉维夫大学有限公司 Antiseptic compositions comprising silver ions and menthol and uses thereof

Non-Patent Citations (1)

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Title
李鹏飞等: "中药及配伍合剂对致病菌的体外抑菌活性的研究", 海南医学, vol. 29, no. 16, pages 2307 *

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