CN114931138B - Sterilization disinfectant and preparation method thereof - Google Patents
Sterilization disinfectant and preparation method thereof Download PDFInfo
- Publication number
- CN114931138B CN114931138B CN202111190850.9A CN202111190850A CN114931138B CN 114931138 B CN114931138 B CN 114931138B CN 202111190850 A CN202111190850 A CN 202111190850A CN 114931138 B CN114931138 B CN 114931138B
- Authority
- CN
- China
- Prior art keywords
- gelatin
- solution
- disinfectant
- chitosan
- microcapsule
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- 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
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/26—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests in coated particulate form
- A01N25/28—Microcapsules or nanocapsules
-
- 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
- A01N33/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds
- A01N33/02—Amines; Quaternary ammonium compounds
- A01N33/12—Quaternary ammonium compounds
-
- 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
- A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
- A01N47/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
- A01N47/42—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides containing —N=CX2 groups, e.g. isothiourea
- A01N47/44—Guanidine; Derivatives thereof
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
- B01J13/06—Making microcapsules or microballoons by phase separation
- B01J13/14—Polymerisation; cross-linking
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Health & Medical Sciences (AREA)
- Dentistry (AREA)
- Zoology (AREA)
- Plant Pathology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Agronomy & Crop Science (AREA)
- Wood Science & Technology (AREA)
- Pest Control & Pesticides (AREA)
- Environmental Sciences (AREA)
- Organic Chemistry (AREA)
- Toxicology (AREA)
- Dispersion Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention provides a sterilizing disinfectant and a preparation method thereof, wherein the effective component of the sterilizing disinfectant is in a microcapsule form, the capsule core is provided with two chemical substances, one of the chemical substances is one of polyhexamethylene guanidine hydrochloride or polyhexamethylene guanidine phosphate, and the other chemical substance is one of benzalkonium chloride or benzalkonium bromide. The microcapsule wall structure has the characteristic of chemical water-soluble gel, can be compatible with soap, anionic surfactant and the like, and overcomes the defect that the application of the conventional polyhexamethylene guanidine salt in washing products is limited because most of washing product formulas in the current market contain anionic surfactant. On the other hand, by wrapping the polyhexamethylene guanidine hydrochloride (phosphate) and benzalkonium chloride (bromide) aqueous solution with sterilizing effect in a capsule wall structure with certain mechanical properties, the capsule wall structure of the microcapsule is destroyed when in use, and the polyhexamethylene guanidine hydrochloride (phosphate) and benzalkonium chloride (bromide) aqueous solution is released for sterilization and disinfection.
Description
Technical Field
The invention relates to the technical field of medical treatment, in particular to a sterilizing disinfectant and a preparation method thereof.
Background
The types of conventional disinfectants are as follows:
1. oxidizing agents
(1) Povidone iodine is commonly known as iodophor, a complex of polyvinylpyrrolidone and iodine. The iodophor is a dark red solution, is odorless, tasteless and free of obvious insoluble substances, and can be mixed with water and ethanol. The iodophor swells the outer membrane layer, the shell layer and the core of the spore by permeation and oxidation, damages the permeability of cell membranes, iodizes bioactive substance molecules contacted with the iodophor to lose activity, and thus, the effect of killing bacteria is achieved. The iodophor has strong bactericidal power and strong disinfecting effect on bacteria, fungi, viruses, spores and the like. It kills bacterial propagules very quickly, but kills spores generally requires a higher concentration and longer time.
(2) The hydrogen peroxide for sterilizing the hydrogen peroxide has the use concentration of 3 percent and is mainly used for sterilizing wounds. When hydrogen peroxide contacts bacteria, free hydroxyl with strong oxidizing ability is formed, the basic molecular structure of protein is destroyed, bacterial thallus is destroyed, and therefore the functions of bacteriostasis and sterilization are achieved. After killing bacteria, green decomposition products water and oxygen are produced, and environmental pollution is avoided. Hydrogen peroxide is therefore an ideal disinfectant.
2. Surfactants
Benzalkonium chloride (bromide) is a quaternary ammonium salt cationic surfactant, and has strong bactericidal performance in various bactericidal surfactants. The benzalkonium chloride (bromide) solution can adsorb bacteria with negative charges, destroy cell membranes of the bacteria, and enable enzymes, coenzyme and metabolic intermediate products in the bacteria to escape, so that bacterial proteins are denatured and precipitated. Has strong antibacterial and bactericidal effects on a plurality of spore pathogenic bacteria, gram positive bacteria and mould, but has weak response to gram negative bacilli and enteroviruses, and is ineffective to tubercle bacilli. The benzalkonium chloride (bromide) has low sterilization concentration, less side reaction, no irritation and difficult volatilization. However, attention should be paid to the effect of hydrogen peroxide and soapy water on the disinfection effect of the disinfectant when using benzalkonium chloride (bromide). The free hydroxyl band formed by hydrogen peroxide has negative charges, and the effective part of benzalkonium chloride (bromide) is a cationic group and has positive charges, and the positive charges and the negative charges are mutually attracted and combined, so that the sterilization effect is obviously reduced. Soap is an anionic detergent, and if it meets benzalkonium chloride (bromide), the sterilizing ability of the disinfectant is weakened or even lost due to the attraction of positive and negative charges.
3. Alcohols
The ethanol belongs to an alcohol-type neutralizing disinfectant, and the ethanol absorbs water of bacterial proteins to dehydrate, denature and solidify the bacterial proteins, so that bacteria are killed. The aqueous solution with a volume fraction of about 75% is the optimal concentration for ethanol to be used as a disinfectant. The reasons are as follows: (1) The ethanol molecule enters the peptide chain link of the bacterial protein molecule to denature and precipitate the protein, and the effect is stronger when the volume fraction of ethanol is 70 percent. (2) disruption of bacterial cell walls: the ethanol has strong permeation effect, and 60% -85% of ethanol can easily permeate into the bacterial body, so that bacterial cells are destroyed and dissolved. (3) disruption of microbial enzyme system: ethanol inhibits normal metabolism and inhibits bacterial growth and reproduction by inhibiting bacterial enzyme systems, particularly dehydrogenases, oxidases and the like. If high-concentration ethanol is used, the bacterial proteins are dehydrated too rapidly, so that the bacterial surface proteins are denatured and coagulated first, a firm coating is formed, and the ethanol can not penetrate into the interior of the bacteria well, so that the sterilization capability of the bacteria is affected. The 75% ethanol is similar to the osmotic pressure of bacteria, and can gradually infiltrate into the interior of the bacterial body before the surface proteins of the bacteria are undenatured, so that all the proteins of the bacteria are dehydrated, denatured and solidified, and finally the bacteria are killed. When the ethanol concentration is less than 75%, the sterilization ability is also affected due to the reduced permeability. The ethanol is nontoxic to human body under the condition of disinfection, but the individual is allergic to the ethanol, and can cause rash and erythema after contacting. Often, ethanol is used for washing hands and disinfecting, which can cause dry and rough skin, and the problem can be solved by adding moisturizing agents such as glycerol, ethylene glycol and the like into the ethanol disinfectant.
4. Organic small molecules
The triclosan is commonly known as triclosan, and the 2,4 '-trichloro-2' -hydroxydiphenyl ether is a broad-spectrum antibacterial agent widely applied at present, and is used in household daily necessities and personal hygiene products due to high sterilization efficiency, no skin irritation and good skin compatibility. Such broad spectrum antimicrobial agents are also widely used in medical instrument disinfectants, disinfection before textile shipment, toys and building materials. Triclosan is white or off-white crystalline powder, has strong surface activity, has phenol odor, is dissolved in organic solvents, and has high stability to strong acid, strong alkali and heat. The basic characteristics of triclosan are represented in the following six aspects. (1) High purity and is not easy to be contaminated by skin and products. (2) Slightly soluble in water, and easily soluble in various organic solvents and surfactants. (3) Easy storage and high stability to strong acid, strong alkali and heat. Can not be rapidly decomposed when stored at high temperature; only slightly decomposed under the irradiation of ultraviolet rays for a long time; the active material is decomposed only by 2% when heated at 200 ℃ for 14 h. (4) Has inhibiting and killing effects on gram positive bacteria, yeast, fungi and viruses. (5) Has no irritation to skin. (6) The method is effective to drug-resistant bacteria and non-drug-resistant bacteria.
5. Polymer compounds
The high molecular disinfectant is a new generation disinfectant, has excellent bactericidal activity, and the advantages are mainly represented in the following steps: high efficiency, safety, no toxic and side effect, and stable light and heat; the bacterial drug resistance is not generated, and the preparation is durable and effective; colorless, odorless, and nonvolatile; the product contains no heavy metal and phenol substances; the method has no corrosion to various treatment surfaces; is environment-friendly.
The common high molecular disinfectant is polyhexamethylene guanidine disinfectant. Polyhexamethylene guanidine disinfectants are classified into biguanide salts and monoguanidine salts. The common biguanide salt is polyhexamethylene biguanide hydrochloride, is generally sold in an aqueous solution with the mass fraction of 20%, and can be used singly or in combination with other types of bactericides. The pH of the system is effectively 4-10, compared with quaternary ammonium salt disinfectant, the odor and foam are reduced to a great extent, and the active ingredients are stable to heat and are not volatilized. Monoguanidine salts are: 1) Polyhexamethylene guanidine hydrochloride. No special smell, easy dissolution in water; the water solution is colorless to pale yellow, odorless and has weak corrosion to metals such as copper, stainless steel, carbon steel and the like; broad-spectrum sterilization and good stability. 2) Polyhexamethylene guanidine stearate. The derivative of the monoguanidine salt disinfectant has good stability, and the antibacterial activity is still good after the derivative is heated for 15min at the high temperature of 280 ℃. 3) Polyhexamethylene guanidine propionate. Has excellent bactericidal effect, low toxicity and no corrosion to metal. Is generally prepared into powder, and has wide application in the fields of plastics, daily chemicals, textiles, water treatment and the like. 4) Polyhexamethylene guanidine phosphate. Phosphate radical is contained, so that the disinfectant has irritation to skin mucosa and eyes and high toxicity, and meanwhile, the phosphorus-containing compound is an algae growth promoter, so that the water body tends to be eutrophicated and the environment is damaged. At present, polyhexamethylene guanidine phosphate is not widely used and is very carefully used internationally. 5) Polyhexamethylene guanidine sulfate. A white powder is odorless, is easily dissolved in water, has no corrosion to metal, has decomposition temperature higher than 400 ℃, has no bleaching phenomenon to the treated surface, and does not deteriorate for two years. The polyhexamethylene monoguanidine salt has similar bactericidal performance with biguanidine salt, the synthetic cost of the monoguanidine salt is lower, the biguanidine salt is milder, the safety is higher, and the bactericidal effect of the hydrochloride is better than that of other salts.
The sterilization mechanism of the polyhexamethylene guanidine salt disinfectant mainly comprises: 1) The guanidine group in the polyhexamethylene guanidine salt has higher activity, and the polymer is electropositive. As various bacteria and viruses are generally electronegative, the polyhexamethylene guanidine salt is easy to adsorb, so that the bacteria and viruses can not be split and propagated, and the activity is lost; 2) Collapse of cell membrane structure to form transmembrane pores, rupture of cell membrane, and destruction of microbial energy metabolism to deactivate bacterial virus; 3) The polymer can form a film to block the respiratory passages of the microorganisms and suffocate the microorganisms to death. The sterilization mechanism is irrelevant to the form and the type of the microorganism, the effect of the microorganism is not affected even if the microorganism is changed or mutated, and the microorganism does not generate drug resistance to the polyhexamethylene guanidine salt.
The existing polyhexamethylene guanidine salt disinfectant has cationic property, is difficult to be compatible with soaps, anionic surfactants and the like, and most of the washing product formulas in the current market contain anionic surfactants, so that the application of the polyhexamethylene guanidine salt in washing products is limited.
Disclosure of Invention
The invention aims to solve the defects in the prior art, and provides a sterilizing disinfectant and a preparation method thereof.
In order to achieve the above purpose, the present invention adopts the following technical scheme: a sterilizing disinfectant, which is characterized in that: the microcapsule comprises a core material, wherein the core material is a microcapsule of polyhexamethylene guanidine hydrochloride (phosphate) and benzalkonium chloride (bromine) aqueous solution, the wall material of the microcapsule is a polymer formed by crosslinking citric acid/genipin and gelatin/chitosan, and the chemical structural formula of the polymer is shown as the formula (I):
in the formula (I), R1 to R9 are selected from eighteen different amino acids of glycine, alanine, serine, aspartic acid, glutamic acid amino, proline, arginine, histidine, tyrosine, cystine, leucine, threonine, methionine, valine, phenylalanine, tryptophan, glutamic acid and lysine.
Preferably, in the formula (I):
r5 and R6 are selected from eighteen residues of different amino acids glycine, alanine, serine, aspartic acid, glutamic acid amino, proline, arginine, histidine, tyrosine, cystine, leucine, threonine, methionine, valine, phenylalanine, tryptophan, glutamic acid and lysine;
r3 and R7 are residues of lysine or arginine;
r2, R4 and R8 are residues of aspartic acid or glutamic acid amino;
r1 and R9 are serine, threonine or tyrosine residues.
The invention also provides a preparation method of the sterilizing disinfectant, which specifically comprises the following steps:
(1) Uniformly mixing glycerol, propylene glycol, water-soluble cherry essence and deionized water;
(2) The microcapsule with core material of polyhexamethylene guanidine hydrochloride and benzalkonium chloride solution is prepared through the specific steps of:
a. dissolving gelatin in acetic acid aqueous solution to obtain gelatin acetic acid solution;
b. adding chitosan into gelatin acetic acid solution, stirring to dissolve chitosan to obtain gelatin/chitosan mixed solution, adding polyhexamethylene guanidine hydrochloride (phosphate) and benzalkonium chloride (bromine) water solution, and regulating pH to 5.8-6.2;
c. adding soybean lecithin as a surfactant into vegetable oil, heating and uniformly stirring;
d. c, adding the gelatin/chitosan mixed solution prepared in the step b into the vegetable oil after the step c for heating and emulsifying, closing heating after the emulsification is completed, and naturally cooling to room temperature;
e. adding genipin into the solution system after the step d to carry out a crosslinking reaction, and fully completing the reaction;
f. adding citric acid and glacial acetic acid into the reaction system after the step e, regulating the pH to 2-3, and adding N 2 Fully reacting under protection to obtain microcapsules with core materials of polyhexamethylene guanidine hydrochloride (phosphate) and benzalkonium chloride (bromine) aqueous solution;
(3) And (3) adding microcapsules, wherein the capsule core material is polyhexamethylene guanidine hydrochloride (phosphate) and benzalkonium chloride (bromine) aqueous solution, into the system in the step (1) to prepare the sterilizing disinfectant.
Preferably, the components in the step (1) are mixed according to the weight parts: 5-10 parts of glycerol, 5-10 parts of propylene glycol and 0.2-0.5 part of water-soluble cherry essence; the ratio of the total mass of the components in the step (1) to the total mass of the components in the step (2) is 1:1.
Preferably, the step f further includes: and d, standing the reaction system after the step f, pouring out the upper oil phase, centrifuging, and separating the oil phase to obtain the microcapsule with the core material of polyhexamethylene guanidine hydrochloride (phosphate) and benzalkonium chloride (bromide) water solution.
Preferably, in step b, the pH is preferably adjusted to 6.
Preferably, the specific steps of the step e are as follows: and d, adding 0.5% genipin aqueous solution into the solution system after the step d, reacting for 3 hours at room temperature, heating to 35 ℃ and reacting for 15 hours again, and fully reacting.
Preferably, the specific steps of the step f are as follows: and e, adding 1% citric acid aqueous solution into the reaction system in the step e, adding glacial acetic acid, regulating the pH to 2-3, heating the reaction temperature to 40 ℃ under the protection of N2, reacting for 8 hours, and then cooling to room temperature to obtain the microcapsule with the core material of polyhexamethylene guanidine hydrochloride (phosphate) and benzalkonium chloride (bromide) aqueous solution.
Preferably, the vegetable oil in the step c is one or more of corn oil, olive oil, soybean oil and peanut oil.
Preferably, the weight portions of the components are as follows: 45-55 parts of gelatin, 3-7 parts of chitosan, 250-350 parts of 1.0% acetic acid solution, 40-60 parts of soybean phospholipid, 30-40 parts of 0.5% genipin water solution, 5-15 parts of 1.0% citric acid solution and 2500-3000 parts of vegetable oil.
Further preferably, the composition comprises, by weight, 50 parts of gelatin, 5 parts of chitosan, 300 parts of 1.0% acetic acid solution, 50 parts of soybean phospholipid, 50 parts of 0.5% genipin aqueous solution, 10 parts of 1.0% citric acid solution and 2700 parts of vegetable oil.
Preferably, the active ingredient of the sterilizing disinfectant is in a microcapsule form, the capsule core material is provided with two chemical substances, one of the chemical substances is one of polyhexamethylene guanidine hydrochloride or polyhexamethylene guanidine phosphate, the other chemical substance is one of benzalkonium chloride or benzalkonium bromide, and the mass ratio of the two chemical substances is 3:1-5:1, and more preferably, the mass ratio of the two chemical substances is 4:1.
Preferably, the core material is 8-12 parts of disinfectant and 350-400 parts of water, and more preferably, the core material is 10 parts of disinfectant and 380 parts of water.
Preferably, the mass ratio of gelatin to chitosan is 8:1 to 12:1, the volume ratio of the water phase to the oil phase is 1:3 to 1:5, a step of; it is further preferable that the mass ratio of gelatin to chitosan is selected to be 10:1, and the volume ratio of water phase to oil phase is selected to be 1:4.
Compared with the prior art, the sterilizing disinfectant has the beneficial effects that the disinfectant contains two chemical substances as the capsule core substance, wherein one of the chemical substances is one of polyhexamethylene guanidine hydrochloride or polyhexamethylene guanidine phosphate, and the other chemical substance is one of benzalkonium chloride or benzalkonium bromide. The microcapsule wall structure has the characteristic of chemical water-soluble gel, can be compatible with soap, anionic surfactant and the like, and overcomes the defect that the application of the conventional polyhexamethylene guanidine salt in washing products is limited because most of washing product formulas in the current market contain anionic surfactant. On the other hand, by wrapping the polyhexamethylene guanidine hydrochloride (phosphate) and the benzalkonium chloride (bromide) aqueous solution in a capsule wall structure with certain mechanical properties, the capsule wall structure of the microcapsule is destroyed when in use, and the polyhexamethylene guanidine hydrochloride (phosphate) and the benzalkonium chloride (bromide) aqueous solution are released for sterilization and disinfection.
Drawings
FIG. 1 is a graph of isoelectric points of gelatin, chitosan, and chitosan/gelatin of example 1 at different mass ratios;
FIG. 2 is a thermogravimetric plot of gelatin, chitosan, gelatin/chitosan complex, genipin cross-linked gelatin/chitosan and citric acid secondary cross-linked gelatin/chitosan.
FIG. 3 is a comparative image of a microcapsule microscope with the core material of example 2 being an aqueous solution of polyhexamethylene guanidine phosphate and benzalkonium chloride.
FIG. 4 is a microscopic image of the microcapsules of example 4 after shearing.
Fig. 5 is a graph showing the bactericidal effect of the bactericidal disinfectant prepared in example 2 on staphylococcus aureus.
FIG. 6 is a graph showing the sterilizing effect of the sterilizing disinfectant prepared in example 2 on Escherichia coli.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention.
EXAMPLE 1 isoelectric point measurement of gelatin, chitosan, gelatin/Chitosan composite
1.1 isoelectric point of gelatin
0.5g of gelatin is weighed, 100ml of deionized water is added, and the mixture is stirred at a water bath temperature of 50 ℃ until the gelatin is completely dissolved, thus obtaining a gelatin solution with the concentration of 0.5%. The pH was adjusted using 0.001mol/L HCl solution and 0.001mol/L NaOH solution, and the conductivity of the gelatin solution at different pH values was recorded using a pH meter and conductivity meter.
1.2 isoelectric point of chitosan
0.5g of chitosan is weighed and added into 100ml of 0.01mol/L HCl solution, and the mixture is stirred at room temperature until the chitosan is completely dissolved, thus obtaining 0.5 percent chitosan solution. The pH of the solution was adjusted using a 0.001mol/L NaOH solution and the conductivity of the gelatin solution at different pH values was recorded using a pH meter and conductivity meter.
1.3 isoelectric point of Chitosan/gelatin composite
100mL of a 1.0% gelatin solution was placed in a beaker and magnetically stirred with a water bath at 50 ℃. Adding a certain volume of 1.0% chitosan solution into the gelatin solution, and stirring for 1h to obtain gelatin/chitosan uniform mixed solution. The volume ratio of chitosan to gelatin is respectively as follows: 4:100, 10:100, 20: 100. 50:100, 75:100, 100:100. The pH of the mixed solution was changed using a 1.0% HCl solution and a 0.1mol/L NaOH solution, and the conductivity of the gelatin/chitosan solution was measured at different pH values using a pH meter and a conductivity meter.
The isoelectric points of the gelatin, the chitosan and the chitosan/gelatin with different mass ratios are measured according to the method shown in the table 1, and the isoelectric point curves of the gelatin, the chitosan and the chitosan/gelatin with different mass ratios are shown in the table 1.
TABLE 1 isoelectric points of gelatin, chitosan and different mass ratios of isoelectric points of chitosan/gelatin
Example 2 preparation method of sterilizing disinfectant
(1) Weighing 8.00g of glycerol, 8.00g of propylene glycol, 0.30g of water-soluble cherry essence and 83.70g of deionized water, stirring for 10-20min, and uniformly mixing;
(2) The microcapsule with the core material of polyhexamethylene guanidine phosphate and benzalkonium chloride water solution is prepared by the following specific steps:
a. weighing 5.00g of gelatin in a beaker, and dissolving 30mL of 1.0% acetic acid aqueous solution at a water bath temperature of 37 ℃;
b. after gelatin is completely dissolved, adding 0.50g of chitosan into gelatin solution, stirring and dissolving to obtain uniform gelatin/chitosan mixed solution, adding polyhexamethylene guanidine phosphate and benzalkonium chloride, and regulating pH to 6 with 5.0% ammonia water solution;
in this step, the pH was adjusted to 6 because gelatin is an amphoteric polymer having an isoelectric point of 5.0 and a pH greater than its isoelectric point, and gelatin molecules were negatively charged, i.e., -NH 3 + Has a part of and-OH - Conversion to-NH by binding 2 whereby-COO in the gelatin molecule - (negative charge) content is greater than-NH 3 + (positively charged) content, the molecule is negatively charged. When gelatin is in a medium less than the isoelectric point, the gelatin molecule becomes positively charged, i.e. -COO - With a part of-H + Binding to-COOH, whereby-NH in a gelatin molecule 3 + A (positive charge) content of greater than-COO - (negative charge) content, the molecule is positively charged. Thus, the pH of the system is regulated to 6, gelatin is negatively charged, chitosan is positively charged due to the protonation of free ammonia genes on the molecules of the chitosan in an acidic medium, and thus the negatively charged gelatin and the positively charged chitosan are subjected toComplex coacervation reactions occur due to electrostatic interactions. The ionization reaction of gelatin at different pH values is shown as the formula:
the protonation reaction process of chitosan in an acidic medium is shown as a formula III:
the complex coacervation reaction of gelatin and chitosan is shown in formula IV:
c. taking 270mL of corn oil in a three-neck flask, adding 5.00g of soybean lecithin, heating to 36 ℃, and uniformly stirring, wherein the soybean lecithin is an amphoteric surfactant which can be extracted from soybeans and is natural and nontoxic;
d. adding gelatin/chitosan mixed solution into corn oil for emulsification at 600rpm and 37 ℃ for 60min;
e. closing heating, and naturally cooling to room temperature; gelatin may undergo sol-gel and gel transition, swelling when the temperature is above 35 ℃, and gelling when the temperature is below 35 ℃. Thereby reducing the temperature to room temperature, being beneficial to forming a relatively fixed shell film of the particles due to gelatin gel, improving the stability of the particles and being beneficial to the next cross-linking reaction;
f. and d, adding 3.50mL of 0.5% genipin solution into the reaction system cooled in the step e, reacting for 3 hours at room temperature, and then heating to 35 ℃ to react for 15 hours.
In the step, genipin can be subjected to a crosslinking reaction with a polymer containing free amino, free amino groups on chitosan and gelatin are subjected to a parent attack on an ethylenic carbon atom at the C-3 position of genipin under an acidic condition, and a dihydropyran ring is opened to form heterocyclic amine; in addition, the ester group on genipin may be reacted with ammoniaRadical generation SN 2 Nucleophilic substitution reaction to form amide and release methanol, so as to form a three-dimensional network structure polymer taking short-chain genipin as a cross-linking bridge; the cross-linking reaction process of genipin and chitosan is shown as a formula V:
g. adding 1%1mL of aqueous solution of citric acid into the reaction system after the step f, adding glacial acetic acid, regulating the pH to 2-3, under the protection of N2, heating the reaction temperature to 40 ℃, reacting for 8 hours, and cooling to room temperature to obtain microcapsules with core materials of polyhexamethylene guanidine phosphate and benzalkonium chloride aqueous solution;
in the step, genipin reacts with free amino groups of gelatin and chitosan to generate crosslinking, free hydroxyl groups exist on chitosan and gelatin molecules, citric acid is added into a reaction system, under certain conditions, carboxyl groups on the citric acid and free hydroxyl groups on macromolecules generate esterification reaction, and the microcapsule taking gelatin and chitosan as capsule walls is subjected to secondary crosslinking, wherein the structural formula is shown as formula I:
h. standing the microcapsule obtained by the reaction for 2 hours, depositing gelatin/chitosan microcapsule on the lower layer, pouring corn oil on the upper layer, pouring out the upper oil phase, taking the lower layer microcapsule, centrifuging, and separating the oil phase to obtain the microcapsule with the core material of polyhexamethylene guanidine phosphate and benzalkonium chloride aqueous solution. Finally transferring the microcapsule into a wide-mouth bottle, and sealing and preserving;
(3) And (3) weighing microcapsules with core materials of polyhexamethylene guanidine phosphate and benzalkonium chloride aqueous solution, adding the microcapsules into the system in the step (1), and stirring for 20-30min to obtain the sterilizing disinfectant.
Example 3 thermogravimetric analysis (TG)
3.1 analytical method
2-6mg of sample is weighed, and is tested by adopting a TG/DSC synchronous thermal analyzer, the temperature is raised from room temperature to 600 ℃ at the speed of 10 ℃/min, and the gas atmosphere is nitrogen.
3.2 analysis results
The thermal decomposition temperatures of the different samples are shown in table 2,
TABLE 2 thermal decomposition temperatures of different samples
Fig. 2 is a thermal weight graph of gelatin, chitosan, gelatin/chitosan complex, genipin cross-linked gelatin/chitosan and citric acid secondary cross-linked microcapsule, and as can be seen from table 2 and fig. 2, the thermal decomposition temperature of the microcapsule obtained by citric acid secondary cross-linking is maximum, reaching 293 ℃, and the thermal stability is higher than that of genipin primary cross-linked gelatin/chitosan. Therefore, the microcapsule wall after citric acid secondary crosslinking has higher strength and better thermal stability.
The reason for the above results is that: the citric acid secondary crosslinking microcapsule is a double crosslinking agent, the genipin is adopted in the first crosslinking, and is a product of hydrolysis of geniposide by beta-glucosidase, so that the citric acid secondary crosslinking microcapsule is an excellent natural biological crosslinking agent. The second cross-linking adopts citric acid which naturally exists in fruits such as lemon and orange, one citric acid molecule contains three carboxyl groups and one hydroxyl group, and under certain reaction conditions, the citric acid can perform esterification reaction with the hydroxyl groups on gelatin and chitosan, and the gelatin/chitosan on the microcapsule wall can be further cross-linked and solidified, so that the strength of the microcapsule wall is improved, and the thermal stability of the microcapsule is improved.
Example 4 optical microscope characterization
A proper amount of the disinfectant prepared in example 2 was sucked up by a pipette onto a glass slide, and was observed under a model WV-CP240/G optical microscope, and photographed for recording.
Fig. 3 shows the morphology of the microcapsule of example 2 in which the core material is an aqueous solution of polyhexamethylene guanidine phosphate and benzalkonium chloride, and as can be seen from fig. 3, in the emulsification stage, the particle diameter of the fine particles gradually becomes smaller and the particle diameter distribution becomes narrower as the emulsification time increases, and when the emulsification time reaches 60min, the particle diameter is smaller and the stability is better, and when the emulsification time continues to extend, the particle diameter distribution of a part of the fine particles becomes larger, and therefore, the emulsification time is preferable to be 60 min. After the emulsification is completed, a cross-linking agent is added for full reaction to obtain the stable microcapsule with the core material of polyhexamethylene guanidine phosphate and benzalkonium chloride aqueous solution.
A small amount of the microcapsules are taken on a glass slide, and sheared by another glass slide, a microscopic image of the sheared microcapsules is shown in fig. 4, and as can be seen from fig. 4, the microcapsules are ruptured after shearing, and the capsule cores flow out. Therefore, when the microcapsule is subjected to shearing force, the microcapsule can be broken, and the polyhexamethylene guanidine phosphate and benzalkonium chloride aqueous solution flows out to complete fixed-point disinfection.
Example 5 bacterial experiment
The experimental method comprises the following steps:
1. main reagent
Tryptone; yeast leaching powder; agar powder; sodium chloride; coli; staphylococcus aureus;
2. main instrument
A vertical pressure steam sterilizer; an oven; an ultra clean bench; a turbidimetry tube; a pipette gun; a culture dish; an alcohol lamp; a conical flask; a centrifuge; centrifuge tubes and the like
3. The main steps are as follows
(1) LB medium:
liquid medium:
10g of tryptone, 5g of yeast extract powder, 10g of sodium chloride and 1000mL of water are weighed into a conical flask, a glass rod is stirred for full dissolution, a conical flask mouth is sealed by a sealing film after dissolution, and the mixture is placed into a vertical pressure steam sterilizer for sterilization at 115 ℃ for 25-30min.
Solid medium:
weighing 10g of tryptone, 5g of yeast extract powder, 20g of agar powder, 10g of sodium chloride and 1000mL of water, adding into a conical flask, stirring with a glass rod under heating condition to dissolve thoroughly, sealing the conical flask mouth with a sealing film after dissolving, placing into a vertical pressure steam sterilizer, and sterilizing at 115 ℃ for 25-30min
(2) Inoculating bacteria:
firing an inoculating loop, slightly touching an original seed by the inoculating loop, inoculating the original seed into a culture medium, culturing for 18h at the constant temperature of 37 ℃, and marking.
(3) 10mL of uncooled solid culture medium is taken by a pipette, placed in a culture dish, uniformly spread and naturally cooled to form the solid culture medium.
(4) Subpackaging bacteria, centrifuging, and spreading bacteria
Centrifuge tubes were placed, each tube added 1mL of the bacteria and media mixture (liquid from the previous step), and the number was centrifuged. Centrifuging, removing supernatant, adding 1mL of physiological saline, comparing with a turbidimetric tube, and diluting with physiological saline by corresponding times to obtain bacteria with required concentration.
(5) 200 mu L of bacterial liquid is taken and beaten into one corner of a solid culture medium, then bacteria are spread by a bacteria spreader, the surface is upwards, the bottom is marked, and the solid culture medium is placed into a 37 ℃ incubator for culturing for 18 hours.
(6) After 18h, observing whether a bacteriostasis area exists on the solid culture medium and photographing.
Experimental results:
the sterilizing effect of the sterilizing disinfectant prepared in example 2 on staphylococcus aureus is shown in fig. 5, and the sterilizing effect of the sterilizing disinfectant prepared in example 2 on escherichia coli is shown in fig. 6. In fig. 5, the uppermost is a zone of inhibition generated by non-microencapsulated sterilizing disinfectant, the middle is a zone of inhibition generated by microencapsulated and ground sterilizing disinfectant, and the lowermost is a zone of inhibition generated by microencapsulated but non-ground sterilizing disinfectant. As can be seen from fig. 5, the sterilizing disinfectant without microencapsulation produces the most excellent sterilizing performance, and the sterilizing disinfectant with microencapsulation and grinding treatment has a smaller sterilizing performance than the sterilizing disinfectant without microencapsulation because grinding cannot ensure the complete rupture of the microcapsules, and the sterilizing disinfectant with microencapsulation and grinding treatment hardly produces the sterilizing performance due to the coating of the wall material. FIG. 6 shows the sterilizing effect on E.coli, wherein the uppermost part is a zone of inhibition generated by the sterilizing disinfectant which is microencapsulated but not ground, the middle part is a zone of inhibition generated by the sterilizing disinfectant which is not microencapsulated, and the lowermost part is a zone of inhibition generated by the sterilizing disinfectant which is microencapsulated and ground. As can be seen from FIG. 6, the same effect was exhibited on Escherichia coli as compared with the bactericidal activity against Staphylococcus aureus.
This experiment demonstrates that: (1) The sterilizing disinfectant has good sterilizing effect on staphylococcus aureus and escherichia coli; (2) The sterilization disinfectant can be successfully coated by microencapsulation; (3) The microcapsule breaks after being stressed, and the capsule core material has sterilizing effect after flowing out.
The foregoing is only a preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art, who is within the scope of the present invention, should make equivalent substitutions or modifications according to the technical scheme of the present invention and the inventive concept thereof, and should be covered by the scope of the present invention.
Claims (10)
1. The preparation method of the sterilizing disinfectant is characterized by comprising the following steps of:
(1) Uniformly mixing glycerol, propylene glycol, water-soluble cherry essence and deionized water;
(2) The microcapsule with core material of polyhexamethylene guanidine hydrochloride and benzalkonium chloride solution is prepared through the specific steps of:
a. dissolving gelatin in acetic acid aqueous solution to obtain gelatin acetic acid solution;
b. adding chitosan into gelatin acetic acid solution, stirring to dissolve chitosan to obtain gelatin/chitosan mixed solution, adding polyhexamethylene guanidine hydrochloride (phosphate) and benzalkonium chloride (bromine) water solution, and regulating pH to 5.8-6.2;
c. adding soybean lecithin as a surfactant into vegetable oil, heating and uniformly stirring;
d. c, adding the gelatin/chitosan mixed solution prepared in the step b into the vegetable oil after the step c for heating and emulsifying, closing heating after the emulsification is completed, and naturally cooling to room temperature;
e. adding genipin into the solution system after the step d to carry out a crosslinking reaction, and fully completing the reaction;
f. adding citric acid and glacial acetic acid into the reaction system after the step e, regulating the pH to 2-3, and adding N 2 Fully reacting under protection to obtain microcapsules with core materials of polyhexamethylene guanidine hydrochloride (phosphate) and benzalkonium chloride (bromine) aqueous solution;
(3) Adding microcapsules, wherein the capsule core material is polyhexamethylene guanidine hydrochloride (phosphate) and benzalkonium chloride (bromine) aqueous solution, into the system in the step (1) to prepare a sterilizing disinfectant;
the wall material of the microcapsule is a polymer formed by crosslinking citric acid/genipin and gelatin/chitosan.
2. The method for preparing the sterilizing disinfectant according to claim 1, wherein the components in the step (1) are mixed according to parts by weight: 5-10 parts of glycerol, 5-10 parts of propylene glycol and 0.2-0.5 part of water-soluble cherry essence; the ratio of the total mass of the components in the step (1) to the total mass of the components in the step (2) is 1:1.
3. The method for preparing a disinfectant as set forth in claim 1, wherein the step f further includes: and d, standing the reaction system after the step f, pouring out the upper oil phase, centrifuging, and separating the oil phase to obtain the microcapsule with the core material of polyhexamethylene guanidine hydrochloride (phosphate) and benzalkonium chloride (bromide) water solution.
4. The method for preparing a disinfectant as set forth in claim 1, wherein the pH is adjusted to 6 in the step b.
5. The method for preparing the sterilizing disinfectant according to claim 1, wherein the specific steps of the step e are as follows: and d, adding 0.5% genipin aqueous solution into the solution system after the step d, reacting for 3 hours at room temperature, heating to 35 ℃ and reacting for 15 hours again, and fully reacting.
6. The method for preparing the sterilizing disinfectant according to claim 1, wherein the specific steps of the step f are as follows: adding 1% citric acid aqueous solution into the reaction system of the step e, adding glacial acetic acid, regulating pH to 2-3, and adding N 2 The reaction temperature is raised to 40 ℃ under protection, after the reaction is carried out for 8 hours, the reaction is cooled to room temperature, and the microcapsule with the core material of polyhexamethylene guanidine hydrochloride (phosphate) and benzalkonium chloride (bromine) aqueous solution is obtained.
7. The method for preparing the sterilizing disinfectant according to claim 1, wherein the vegetable oil in the step c is one or more of corn oil, olive oil, soybean oil and peanut oil.
8. The method for preparing the sterilizing disinfectant according to claim 1, wherein the sterilizing disinfectant is characterized by comprising the following components in parts by weight: 45-55 parts of gelatin, 3-7 parts of chitosan, 250-350 parts of 1.0% acetic acid solution, 40-60 parts of soybean phospholipid, 30-40 parts of 0.5% genipin water solution, 5-15 parts of 1.0% citric acid solution and 2500-3000 parts of vegetable oil.
9. A disinfectant prepared by the method for preparing a disinfectant as set forth in any one of claims 1 to 8, characterized in that: the microcapsule comprises a core material, wherein the core material is a microcapsule of polyhexamethylene guanidine hydrochloride (phosphate) and benzalkonium chloride (bromine) aqueous solution, the wall material of the microcapsule is a polymer formed by crosslinking citric acid/genipin and gelatin/chitosan, and the chemical structural formula of the polymer is shown as the formula (I):
in formula (I): r is R 1 To R 9 Is selected from eighteen different amino acids of glycine, alanine, serine, aspartic acid, glutamic amino, proline, arginine, histidine, tyrosine, cystine, leucine, threonine, and egg ammoniaResidues of one of acid, valine, phenylalanine, tryptophan, glutamic acid and lysine.
10. The disinfectant as set forth in claim 9, wherein in the formula (I):
R 5 、R 6 residues selected from eighteen different amino acids glycine, alanine, serine, aspartic acid, glutamic acid amino group, proline, arginine, histidine, tyrosine, cystine, leucine, threonine, methionine, valine, phenylalanine, tryptophan, glutamic acid and lysine;
R 3 、R 7 residues that are lysine or arginine;
R 2 、R 4 、R 8 residues that are aspartic acid or glutamic acid amino groups;
R 1 、R 9 residues that are serine, threonine or tyrosine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111190850.9A CN114931138B (en) | 2021-10-13 | 2021-10-13 | Sterilization disinfectant and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111190850.9A CN114931138B (en) | 2021-10-13 | 2021-10-13 | Sterilization disinfectant and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114931138A CN114931138A (en) | 2022-08-23 |
| CN114931138B true CN114931138B (en) | 2023-10-20 |
Family
ID=82861803
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111190850.9A Active CN114931138B (en) | 2021-10-13 | 2021-10-13 | Sterilization disinfectant and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114931138B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115956573A (en) * | 2022-12-15 | 2023-04-14 | 江苏维尤纳特精细化工有限公司 | Novel bactericidal composition containing chlorothalonil |
| CN117660125B (en) * | 2023-10-20 | 2024-05-28 | 广东星帮尼科技股份有限公司 | Quaternary ammonium salt clothes cleaning disinfectant and preparation method thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101028529A (en) * | 2006-02-27 | 2007-09-05 | 权力敏 | Antiseptics for planting edible mushroom |
| CN101027999A (en) * | 2006-02-27 | 2007-09-05 | 权力敏 | Agricultural bacteriocide |
| CN105175799A (en) * | 2015-05-27 | 2015-12-23 | 青岛农业大学 | Highly stable protein-chitosan complex coacervation crosslinked microcapsule and preparation method thereof |
| CN106035361A (en) * | 2016-05-23 | 2016-10-26 | 中国人民武装警察部队总医院 | Compound quaternary ammonium salt disinfection solution, and preparation method and application thereof |
| CN106581654A (en) * | 2016-12-27 | 2017-04-26 | 青岛琛蓝海洋生物工程有限公司 | Composite skin wound disinfectant and preparation method thereof |
| CN112088879A (en) * | 2020-10-19 | 2020-12-18 | 武汉东湖星科技有限公司 | Quaternary ammonium salt compound disinfectant and preparation method thereof |
-
2021
- 2021-10-13 CN CN202111190850.9A patent/CN114931138B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101028529A (en) * | 2006-02-27 | 2007-09-05 | 权力敏 | Antiseptics for planting edible mushroom |
| CN101027999A (en) * | 2006-02-27 | 2007-09-05 | 权力敏 | Agricultural bacteriocide |
| CN105175799A (en) * | 2015-05-27 | 2015-12-23 | 青岛农业大学 | Highly stable protein-chitosan complex coacervation crosslinked microcapsule and preparation method thereof |
| CN106035361A (en) * | 2016-05-23 | 2016-10-26 | 中国人民武装警察部队总医院 | Compound quaternary ammonium salt disinfection solution, and preparation method and application thereof |
| CN106581654A (en) * | 2016-12-27 | 2017-04-26 | 青岛琛蓝海洋生物工程有限公司 | Composite skin wound disinfectant and preparation method thereof |
| CN112088879A (en) * | 2020-10-19 | 2020-12-18 | 武汉东湖星科技有限公司 | Quaternary ammonium salt compound disinfectant and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114931138A (en) | 2022-08-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN114931138B (en) | Sterilization disinfectant and preparation method thereof | |
| EP1111995B1 (en) | Topical dermal antimicrobial compositions | |
| JP3692301B2 (en) | Polymer compound and method for formulating the same | |
| KR20190059265A (en) | Polymer-based antibiotic components and methods for their use | |
| CN100407923C (en) | Sterilization disinfectant and application thereof | |
| US20080181951A1 (en) | Treatment of humans with colloidal silver composition | |
| JP2005531637A (en) | Disinfecting composition | |
| CN113351125B (en) | Citrus essential oil microcapsule and preparation method and application thereof | |
| UA53683C2 (en) | Bactericidal composition | |
| EP2706845B1 (en) | Antimicrobial solid and methods of making and using same | |
| Ibrahim et al. | Antimicrobial agents for textiles: types, mechanisms and analysis standards | |
| JP2001508041A (en) | Contact killing / non-leaching antibacterial material | |
| WO2016039812A1 (en) | Compositions for photodynamic control of infection | |
| CN113491709B (en) | Multifunctional high-efficiency compound disinfectant and preparation method thereof | |
| CN115997795B (en) | Bactericide for cleaning and disinfecting factory conveying pipeline and preparation method and application thereof | |
| CN112021340A (en) | Preparation and application of nano composite bactericidal antiviral material | |
| AU2006207365B2 (en) | Formulation | |
| CN111500490A (en) | Microbial type bacteriostatic and odor-removing preparation as well as preparation method and application thereof | |
| WO2022094924A1 (en) | Antibacterial antiviral microcapsule, preparation method therefor and application thereof | |
| CN114431229A (en) | Antibacterial and antiviral microcapsule and preparation method and application thereof | |
| EP1044689A1 (en) | Solid iodophor preparations and process for producing the same | |
| CN106035324A (en) | Preparation method of microcapsule mosquito-repellent incense liquid containing meperfluthrin | |
| CN116966115B (en) | Long-acting antibacterial pet cleaning care agent and preparation method thereof | |
| CN114831134B (en) | Platinum nano-particle/short peptide hydrogel and preparation method and antibacterial application thereof | |
| CN114431250B (en) | Disinfectant, and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information |
Address after: J2, 2nd Floor, Building 1, No. 225 Loujiang North Road, Taicang City, Suzhou City, Jiangsu Province, 215000 Applicant after: Tuoteng Huabao (Suzhou) Biotechnology Co.,Ltd. Address before: 518000 17e, building 36-39, Qianhai garden, 288 Taoyuan Road, Qianhai community, Nantou street, Nanshan District, Shenzhen City, Guangdong Province Applicant before: Shenzhen Huabao biomaterial Technology Co.,Ltd. |
|
| CB02 | Change of applicant information | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |