CN111214409A - No-clean disinfectant and preparation method thereof - Google Patents
No-clean disinfectant and preparation method thereof Download PDFInfo
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- CN111214409A CN111214409A CN202010155856.1A CN202010155856A CN111214409A CN 111214409 A CN111214409 A CN 111214409A CN 202010155856 A CN202010155856 A CN 202010155856A CN 111214409 A CN111214409 A CN 111214409A
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- triclosan
- folium artemisiae
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9789—Magnoliopsida [dicotyledons]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/347—Phenols
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/43—Guanidines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
- A61K8/4946—Imidazoles or their condensed derivatives, e.g. benzimidazoles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/005—Antimicrobial preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/10—Washing or bathing preparations
Abstract
The invention provides a no-clean disinfectant and a preparation method thereof. The no-clean disinfectant provided by the invention comprises the following components in percentage by mass: 1-10% of folium artemisiae argyi extract, 1-10% of cortex dictamni extract, 0.001-0.005 thousandth of silver ions, 0.1-2% of triclosan, 0.3-5% of chlorhexidine acetate, 0.3-5% of allantoin and the balance of water. The washing-free disinfectant provided by the invention takes the folium artemisiae argyi extract and the cortex dictamni extract as main components, has no stimulation to skin and mucous membrane, can effectively inhibit staphylococcus aureus, escherichia coli and candida albicans, further improves the sterilization effect by adding trace silver ions, a small amount of triclosan and chlorhexidine acetate to be matched with various plant extracts, and further moistens the skin and reduces the stimulation by adding allantoin.
Description
Technical Field
The invention relates to the technical field of sterilization liquid, in particular to a no-clean disinfection liquid and a preparation method thereof.
Background
The hand-washing-free disinfectant popular in the market at present is compounded by taking ethanol as a main sterilization component, and can damage skin and cause canceration in the repeated use process; in addition, the volatilization of the ethanol can bring away a large amount of moisture on the skin, so that the skin is lack of water, and the skin is itchy, dry and even desquamate. Especially, medical staff frequently use, to medical staff skin, hand formation damage and ulcer, and especially medical staff clinical medical barrier gown forms airtight space for a long time, and traditional exempt from liquid soap again to form the damage to the air and the mucosa of breathing in the protective clothing. In addition, the traditional disinfectant contains antibiotics, so that the immunity of a human body is reduced, and 'super bacteria' are generated.
In order to avoid the use of antibiotics, the prior art is beginning to develop plant or traditional Chinese medicine component washing-free disinfectant. For example, Chinese patent CN110151931A discloses a botanical compound no-clean disinfectant, which is prepared by using a plurality of traditional Chinese medicines as raw materials and carrying out soaking, distillation and fermentation treatment, and has better deodorization, sulfur dioxide removal and antibacterial effects. However, the no-clean disinfectant is used for environmental sterilization and cannot be used for skin sterilization. For another example, chinese patent CN108245549A discloses a skin washing-free disinfectant, its preparation method and storage method, wherein the raw materials of the skin washing-free disinfectant include astragalus root extract and levofloxacin, which can be used for preventing wound infection and skin repair. However, the no-clean disinfectant also contains antibiotic components, and the preparation process is complicated when traditional Chinese medicine components are adopted, and the traditional Chinese medicine has poor smell, so that the no-clean disinfectant cannot be accepted by wide consumers.
Therefore, it is necessary to provide a no-clean disinfectant solution which does not contain antibiotics and corrosive residues, does not damage respiratory tract and skin, and can be used for skin sterilization and nursing repair.
Disclosure of Invention
The invention aims to provide a no-clean disinfectant and a preparation method thereof. The no-clean disinfectant provided by the invention does not contain antibiotics, can be used for skin sterilization, and can effectively inhibit staphylococcus aureus, escherichia coli, candida albicans and the like.
The invention provides a no-clean disinfectant, which comprises the following components in parts by mass: 1-10% of folium artemisiae argyi extract, 1-10% of cortex dictamni extract, 0.001-0.005 thousandth of silver ions, 0.1-2% of triclosan, 0.3-5% of chlorhexidine acetate, 0.3-5% of allantoin and the balance of water.
Preferably, the no-clean disinfection solution comprises the following components in percentage by mass: 2-8% of folium artemisiae argyi extract, 2-8% of cortex dictamni extract, 0.0015-0.0045 thousandths of silver ions, 0.3-1.5% of triclosan, 0.5-3% of chlorhexidine acetate, 0.5-3% of allantoin and the balance of water.
Preferably, the no-clean disinfection solution comprises the following components in percentage by mass: 3-6% of folium artemisiae argyi extract, 3-6% of cortex dictamni extract, 0.002-0.004 thousandth of silver ions, 0.5-1% of triclosan, 0.8-2% of chlorhexidine acetate, 0.8-1.5% of allantoin and the balance of water.
Preferably, the no-clean disinfection solution comprises the following components in percentage by mass: 4-5% of folium artemisiae argyi extract, 4-5% of cortex dictamni extract, 0.003-0.0035% of silver ions, 0.6-0.8% of triclosan, 1-1.5% of chlorhexidine acetate, 1-1.2% of allantoin and the balance of water.
Preferably, the content of eucalyptol in the folium artemisiae argyi extract is more than 0.05%.
Preferably, the content of obacunone in the cortex dictamni extracting solution is more than 0.15%.
The invention also provides a preparation method of the no-wash disinfectant in the technical scheme, which comprises the step of mixing the folium artemisiae argyi extract, the cortex dictamni extract, the silver source, the triclosan, the chlorhexidine acetate, the allantoin and water to obtain the no-wash disinfectant.
Preferably, the mixing is performed under stirring conditions.
Preferably, the silver source comprises one or more of nano silver and a silver salt.
Preferably, the folium artemisiae argyi extract, the cortex dictamni extract, the silver source, the triclosan, the chlorhexidine acetate, the allantoin and the water are mixed as follows:
mixing triclosan with part of water at 70-80 ℃ to obtain a triclosan solution;
mixing a silver source with part of water to obtain a silver ion solution;
mixing the triclosan solution and the silver ion solution with the other components to obtain the no-clean disinfectant.
The invention provides a no-clean disinfectant, which comprises the following components in percentage by mass: 1-10% of folium artemisiae argyi extract, 1-10% of cortex dictamni extract, 0.001-0.005 thousandth of silver ions, 0.1-2% of triclosan, 0.3-5% of chlorhexidine acetate, 0.3-5% of allantoin and the balance of water. The skin disinfectant provided by the invention takes the folium artemisiae argyi extract and the cortex dictamni extract as main components, has no stimulation to skin and mucous membrane, can effectively kill staphylococcus aureus, escherichia coli and candida albicans, further improves the sterilization effect by adding trace silver ions, a small amount of triclosan and chlorhexidine acetate to be matched with various plant extracts, and further adds allantoin to moisten the skin, reduce stimulation and accelerate the healing of the skin.
In addition, the preparation method of the no-clean disinfectant provided by the invention is simple, has no special requirements on production devices and processes, and is suitable for large-scale industrial production.
Detailed Description
The invention provides a no-clean disinfectant, which comprises the following components in percentage by mass: 1-10% of folium artemisiae argyi extract, 1-10% of cortex dictamni extract, 0.001-0.005 thousandth of silver ions, 0.1-2% of triclosan, 0.3-5% of chlorhexidine acetate, 0.3-5% of allantoin and the balance of water.
In the invention, the no-clean disinfectant comprises 1-10% by mass of folium artemisiae argyi extract, preferably 2-8%, more preferably 3-6%, and even more preferably 4-5%. The source of the folium artemisiae argyi extract is not particularly limited in the present invention, and the folium artemisiae argyi extract can be prepared by using a commercially available product well known to those skilled in the art or according to a preparation method well known to those skilled in the art. In the invention, the folium artemisiae argyi extract has broad-spectrum antibacterial property, has obvious bactericidal action on staphylococcus aureus, escherichia coli, bacillus subtilis, candida albicans and aspergillus niger, has an anti-inflammatory action, and has no irritation when being used for disinfecting the surface of skin.
In the present invention, the content of eucalyptol in the folium artemisiae argyi extract is preferably more than 0.05%, and more preferably 0.1% or more. In the invention, the eucalyptol exists in the folium artemisiae argyi extract and has the effects of relieving fever, diminishing inflammation, resisting bacteria, preventing corrosion and easing pain.
In the invention, the no-clean disinfectant comprises 1-10% by mass of cortex dictamni extract, preferably 2-8%, more preferably 3-6%, and even more preferably 4-5%. The source of the extract of cortex dictamni is not particularly limited in the present invention, and the extract can be prepared by using a commercially available product well known to those skilled in the art or according to a preparation method well known to those skilled in the art. In the invention, the cortex dictamni extract has obvious inhibition effect on escherichia coli, staphylococcus aureus and candida albicans.
In the present invention, the content of obacunone in the cortex dictamni extract is preferably 0.15% or more, and more preferably 0.3% or more.
In the invention, the no-clean disinfectant comprises silver ions with the mass content of 0.001-0.005 per thousand, preferably 0.0015-0.0045 per thousand, more preferably 0.002-0.004 per thousand, and even more preferably 0.003-0.0035 per thousand. In the invention, the silver ions have broad-spectrum antibacterial and bactericidal effects, can effectively inhibit and kill nearly 600 bacteria, almost covers all bacteria, does not produce drug-resistant strains, and has the characteristics of nature and no toxicity.
In the invention, the no-clean disinfectant comprises 0.1-2% by mass of triclosan, preferably 0.3-1.5%, more preferably 0.5-1%, and even more preferably 0.6-0.8%. The source of the triclosan in the present invention is not particularly limited, and it can be prepared by commercially available products well known to those skilled in the art or by preparation methods well known to those skilled in the art. In the present invention, the triclosan is a broad-spectrum antimicrobial agent, which is effective in killing various microorganisms in combination with various plant extracts.
In the invention, the no-clean disinfectant comprises chlorhexidine acetate with the mass content of 0.3-5%, preferably 0.5-3%, more preferably 0.8-2%, and more preferably 1-1.5%. The source of chlorhexidine acetate is not particularly limited in the present invention, and the chlorhexidine acetate can be prepared by using a commercially available product well known to those skilled in the art, or by a preparation method well known to those skilled in the art. In the invention, the chlorhexidine acetate can kill staphylococcus aureus, escherichia coli and candida albicans, has small irritation, wide sterilization range and stable performance, and can be used for disinfecting skin and mucous membrane.
In the invention, the no-clean disinfectant comprises 0.3-5% of allantoin by mass, preferably 0.5-3%, more preferably 0.8-2%, and even more preferably 1-1.5%. The source of the present invention is not particularly limited, and the present invention may be prepared by using commercially available products known to those skilled in the art, or by preparing methods known to those skilled in the art. In the present invention, allantoin has physiological functions of promoting cell growth, accelerating wound healing, softening keratin, etc., is a good healing agent and anti-ulcer agent for skin wounds, and has bactericidal action.
In addition to the above components, in the present invention, the leave-on disinfectant includes the balance of water. In the present invention, the water is preferably deionized water. In the invention, the water can fully dissolve all components, and good sterilization effect is realized.
The no-clean disinfectant provided by the invention adopts the plant components of the folium artemisiae argyi extract and the cortex dictamni extract, overcomes the smoking defect of the folium artemisiae argyi, avoids the problem of excessive silver metal due to the addition of trace silver ions, improves the disinfection stability of the formula due to the intervention of a proper amount of triclosan, further stabilizes the disinfection effect due to the addition of chlorhexidine acetate and allantoin, enlarges the sterilization variety and overcomes the defect of single raw material disinfection, so that the no-clean disinfectant can be used for disinfecting skin and mucous membranes.
The invention also provides a preparation method of the no-wash disinfectant in the technical scheme, which comprises the step of mixing the folium artemisiae argyi extract, the cortex dictamni extract, the silver source, the triclosan, the chlorhexidine acetate, the allantoin and water to obtain the no-wash disinfectant.
In the present invention, the silver source preferably includes one or more of nano silver and a silver salt.
In the present invention, the mixing is preferably performed under stirring conditions. The operation of stirring is not particularly limited in the present invention, and a stirring technique known to those skilled in the art may be employed.
In the invention, the mixture of the folium artemisiae argyi extract, the cortex dictamni extract, the silver source, the triclosan, the chlorhexidine acetate, the allantoin and the water is as follows:
mixing triclosan with part of water at 70-80 ℃ to obtain a triclosan solution;
mixing a silver source with part of water to obtain a silver ion solution;
mixing the triclosan solution and the silver ion solution with the other components to obtain the no-clean disinfectant.
The no-clean disinfectant provided by the invention takes plant extracts as main components, does not contain antibiotics, has no stimulation to skin, can be used for skin sterilization, and has remarkable sterilization effect on staphylococcus aureus, escherichia coli and candida albicans.
In order to further illustrate the present invention, the following examples are provided to describe the no-clean disinfectant and the preparation method thereof in detail, but they should not be construed as limiting the scope of the present invention.
Example 1:
according to the following mixture ratio, 2% of folium artemisiae argyi extract, 2% of cortex dictamni extract, 0.001 thousandth of nano silver (silver ion), 0.2% of triclosan, 0.5% of chlorhexidine acetate, 0.4% of allantoin and the balance of water are mixed under stirring to obtain the washing-free disinfectant.
The specific mixing is as follows: mixing triclosan with water with the same mass at 70 ℃ to obtain a triclosan solution;
mixing a silver source with part of water to obtain a silver ion solution;
mixing the triclosan solution and the silver ion solution with the other components to obtain the no-clean disinfectant.
Example 2:
according to the following mixture ratio, 4% of folium artemisiae argyi extract, 4% of cortex dictamni extract, 0.002% of nano silver (silver ion, 0.002 per mill), 0.8% of triclosan, 1% of chlorhexidine acetate, 1% of allantoin and the balance of water are mixed under stirring to obtain the no-wash disinfectant, and the specific mixing mode is the same as that of the example 1.
Example 3:
according to the following mixture ratio, 6% of folium artemisiae argyi extract, 6% of cortex dictamni extract, silver salt (silver ion 0.003 ‰), 1% of triclosan, 2% of chlorhexidine acetate, 1.5% of allantoin and the balance of water are mixed under stirring to obtain the no-wash disinfectant, and the specific mixing mode is the same as that of the example 1.
Example 4:
according to the following mixture ratio, 8% of folium artemisiae argyi extract, 8% of cortex dictamni extract, silver salt (silver ion 0.0045 thousandths), 1.5% of triclosan, 3% of chlorhexidine acetate, 3% of allantoin and the balance of water are mixed under stirring conditions to obtain the no-wash disinfectant, and the specific mixing mode is the same as that of the example 1.
Example 5:
according to the following mixture ratio, 10% of folium artemisiae argyi extract, 10% of cortex dictamni extract, 2% of triclosan (silver ion 0.005 thousandth), 5% of chlorhexidine acetate, 5% of allantoin and the balance of water are mixed under stirring to obtain the no-wash disinfectant, and the specific mixing mode is the same as that of the embodiment 1.
The bactericidal performance of the no-clean disinfectant of the embodiment 1-5 is tested, and the specific test method is as follows:
(I) Material and Strain
1. And (3) testing a sample: the no-clean disinfectant of the embodiments 1-5 of the present invention
2. The strain is as follows: escherichia coli (ATCC8099), Candida albicans (ATCC10231) for 9 generations, Staphylococcus aureus (ATCC6538) for 9 generations, and Escherichia coli (ATCC8099) for 9 generations.
(II) method
1. The inspection basis is as follows: GB15979-2002 hygienic Standard for Disposable sanitary articles appendix C4, Disinfection Specification 2002 edition 2.1.8.
2. And (3) sterilization test: washing 24h slant culture of test bacteria with PBS to obtain bacterial suspension, respectively taking out 100 μ L, adding into test tube containing 5mL sample solution and control sample solution (PBS), mixing 4 tubes, acting at 20 + -2 deg.C for 10min, respectively adding 0.5mL sample solution and control sample solution into test tube containing 5mL PBS, mixing, diluting, respectively placing 0.5mL into 2 plates, culturing with nutrient agar culture medium (bacteria) or Sabouraud's agar culture medium (fungi) (35 + -2 deg.C) for 48h (bacteria) or 72h (fungi), and counting viable bacteria colony. The test was repeated 3 times and the sterilization rate was calculated. The nutrient agar culture medium and the Sabouraud agar culture medium are provided by Beijing road bridge technology, Inc. PBS was 0.03mol/L phosphate buffer.
TABLE 1 Sterilization test results after 10min of action
| Rate of sterilization | Staphylococcus aureus (%) | Escherichia coli (%) | Candida albicans (%) |
| Example 1 | 99.5 | 99.2 | 99.9 |
| Example 2 | 99.5 | 99.0 | 99.0 |
| Example 3 | 99.9 | 99.9 | 99.9 |
| Example 4 | 99.1 | 99.2 | 99.2 |
| Example 5 | 99.99 | 99.99 | 99.99 |
The embodiments show that the no-clean disinfectant provided by the invention has a remarkable bactericidal effect on staphylococcus aureus, escherichia coli and candida albicans.
The foregoing is merely a preferred embodiment of the invention and is not intended to limit the invention in any manner. It should be noted that, for those skilled in the art, without departing from the principle of the present invention, several improvements and modifications can be made, and these improvements and modifications should also be construed as the protection scope of the present invention.
Claims (10)
1. The no-clean disinfectant comprises the following components in percentage by mass: 1-10% of folium artemisiae argyi extract, 1-10% of cortex dictamni extract, 0.001-0.005 thousandth of silver ions, 0.1-2% of triclosan, 0.3-5% of chlorhexidine acetate, 0.3-5% of allantoin and the balance of water.
2. The no-clean disinfection solution as claimed in claim 1, which comprises the following components by mass: 2-8% of folium artemisiae argyi extract, 2-8% of cortex dictamni extract, 0.0015-0.0045 thousandths of silver ions, 0.3-1.5% of triclosan, 0.5-3% of chlorhexidine acetate, 0.5-3% of allantoin and the balance of water.
3. The no-clean disinfection solution as claimed in claim 2, which comprises the following components by mass: 3-6% of folium artemisiae argyi extract, 3-6% of cortex dictamni extract, 0.002-0.004 thousandth of silver ions, 0.5-1% of triclosan, 0.8-2% of chlorhexidine acetate, 0.8-1.5% of allantoin and the balance of water.
4. The no-clean disinfection solution as claimed in claim 3, which comprises the following components by mass: 4-5% of folium artemisiae argyi extract, 4-5% of cortex dictamni extract, 0.003-0.0035% of silver ions, 0.6-0.8% of triclosan, 1-1.5% of chlorhexidine acetate, 1-1.2% of allantoin and the balance of water.
5. The no-clean disinfectant as claimed in any one of claims 1-4, wherein the content of eucalyptol in the folium artemisiae argyi extract is greater than 0.05%.
6. The no-clean disinfectant as claimed in any one of claims 1-4, wherein the content of obacunone in the cortex dictamni extract is more than 0.15%.
7. The method for preparing the no-clean disinfection solution as claimed in any one of claims 1 to 6, which comprises mixing folium artemisiae argyi extract, cortex dictamni extract, silver source, triclosan, chlorhexidine acetate, allantoin and water to obtain the no-clean disinfection solution.
8. The method of claim 7, wherein the silver source comprises one or more of nano-silver and a silver salt.
9. The method of claim 7 or 8, wherein the mixing is performed under stirring.
10. The method of claim 7, wherein the combination of the folium artemisiae argyi extract, the cortex dictamni extract, the silver source, the triclosan, the chlorhexidine acetate, the allantoin and the water is:
mixing triclosan with part of water at 70-80 ℃ to obtain a triclosan solution;
mixing a silver source with part of water to obtain a silver ion solution;
mixing the triclosan solution and the silver ion solution with the other components to obtain the no-clean disinfectant.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114522110A (en) * | 2021-12-17 | 2022-05-24 | 安信生物科技有限公司 | Silver ion washing-free disinfectant, and preparation method and application thereof |
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| CN106074291A (en) * | 2016-07-25 | 2016-11-09 | 湖北艾源蕲艾科技有限公司 | A kind of Artemisia argyi Levl. et Van. var. argyi cv. Qiai bacteriostatic lotion |
| CN108904621A (en) * | 2018-07-18 | 2018-11-30 | 湖北惠春蕲艾健康产业发展有限公司 | A kind of Chinese mugwort bacteriostatic lotion and preparation method thereof |
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| CN114522110A (en) * | 2021-12-17 | 2022-05-24 | 安信生物科技有限公司 | Silver ion washing-free disinfectant, and preparation method and application thereof |
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Application publication date: 20200602 |