CN102405935B - Protamine compounded preparation, preparation method and application thereof - Google Patents
Protamine compounded preparation, preparation method and application thereof Download PDFInfo
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- CN102405935B CN102405935B CN2011103337140A CN201110333714A CN102405935B CN 102405935 B CN102405935 B CN 102405935B CN 2011103337140 A CN2011103337140 A CN 2011103337140A CN 201110333714 A CN201110333714 A CN 201110333714A CN 102405935 B CN102405935 B CN 102405935B
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- 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
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Abstract
The invention discloses protamine compounded preparation, a preparation method and application thereof. The protamine compounded preparation of the invention can be singly prepared with the protamine and chitosan, or prepared by compounding one or mixture of over two of glycine, sodium acetate, undecynol monoglyceride, acetic acid, absolute alcohol, lysostaphin, lysozyme, anti-bacterial peptide and sterilized distilled water. The method for preparing the protamine compounded preparation comprises the following steps: accurately weighting each component according to rate in aseptic or clean workshops; putting in clean glass or stainless steel, and uniformly stirring; and sealing in sterile containers. The product not only effectively kills the gram-positive cocci, such as staphyloccocus aureus rosenbach, monilia albican, neisseria gonorrhoeae, streptococcus, anaerobic bacteria, pseudomonas aeruginosa, escherichia coli, pneumococcus, D enterococcus, staphylococcus tetragenus, listeria monocytogenes, stenotrophomonas maltophilia and stomach helicobacter pylori, but also kills the gram-negative bacteria.
Description
Technical field
The present invention relates to a kind of nucleoprotamine complex preparation, the invention still further relates to a kind of method for preparing this nucleoprotamine complex preparation, the invention still further relates to the application of this nucleoprotamine complex preparation.
Background technology
Traditional in the market disinfectant major part is to contain chemical reagent such as chlorine, alcohols, allusion quotation class, aldehydes, phenols.Make it phenol, acid, the alcohols that sex change is sterilized as coagulated protein; The sodium hydroxide of solubilising protein, lime etc.; The bleaching powder of strong oxidation, Peracetic acid etc.; Formalin is combined with protein amino, sterilization reagent such as glutaraldehyde and microprotein reaction.
More than there are following one or more shortcomings in the sterilization reagent overwhelming majority:
1, the sterilization patient there is residual, toxic side effect.
2, mucocutaneous, wound and the surface of a wound there is intense stimulus.
3, be difficult for degraded, corrosion is arranged, discharging has pollution to environment.
4, cost height, at the bottom of the efficient, time-consuming.
Antibiotic (antibiotic) is abused in a large number in China, bacterium constantly hydrolyzing penicillin or ammonia benzyl or cephalo, macrocyclic lactone, quinoline if antibiotic such as ketones, because antibiotic resistance makes the effect of its medicinal effects more and more weakened, on the other hand, antibiotic prolonged application also can impel the drug-fast bacterial strain of high expressed to become dominant microflora gradually, and make bacterial strain more and more difficulty be suppressed or kill.Abusing of antibiotic not only makes bacterial strain produce drug resistance, and very big to the human body toxic and side effect.
Thereby need a kind ofly also need a kind of alternative antibiotic, but broad-spectrum sterilization, and the difficult bactericide that produces endurance strain solves above unfavorable factor.
Summary of the invention
Technical problem to be solved of the present invention is to overcome weak point of the prior art, a kind of safe without toxic side effect is provided, be difficult for producing drug resistance, efficiently, the nucleoprotamine complex preparation of broad-spectrum sterilization, said preparation can make an addition to respectively in external application medicine (comprising skin, mucous membrane), health food, disinfectant for external use, the toothpaste.
Another object of the present invention provides a kind of method for preparing above-mentioned nucleoprotamine complex preparation.
A further object of the invention provides a kind of application of this nucleoprotamine complex preparation.
In order to achieve the above object, the present invention adopts following scheme:
Nucleoprotamine complex preparation of the present invention, can be made separately by nucleoprotamine, shitosan, also can with glycine, sodium acetate, monoglyceride, acetic acid, absolute alcohol, molten glucose coccus enzyme, lysozyme, bacteriostatic peptide, sterile purified water in one or more the composite composition of mixture.
The composite system of a kind of nucleoprotamine is characterized in that comprising by weight percentage following component:
Nucleoprotamine 0.01-99.99%
Water soluble chitosan 0.01-99.99%.
Aforesaid a kind of nucleoprotamine complex preparation is characterized in that composed of the following components by weight percentage:
Aforesaid a kind of nucleoprotamine complex preparation is characterized in that composed of the following components by weight percentage:
Aforesaid a kind of nucleoprotamine complex preparation is characterized in that composed of the following components by weight percentage:
Nucleoprotamine 0.01-10%
Water soluble chitosan 0.01-10%
Sterile purified water 80-99%.
Aforesaid a kind of nucleoprotamine complex preparation is characterized in that composed of the following components by weight percentage:
Aforesaid a kind of nucleoprotamine complex preparation is characterized in that comprising by weight percentage following component:
Aforesaid a kind of nucleoprotamine complex preparation is characterized in that composed of the following components by weight percentage:
1, a kind of nucleoprotamine complex preparation according to claim 3 is characterized in that composed of the following components by weight percentage:
Aforesaid nucleoprotamine complex preparation is characterized in that said preparation can be made into aerosol, aqueous solvent, granule, spray, patch, liniment, a kind of in the mouth spraying agent.
Nucleoprotamine complex preparation of the present invention is used in external application medicine, oral drugs, ear medicine, nose medicine, vitamins, daily use chemicals.
The application of protamine complex preparation of the present invention on health food.
At nucleoprotamine complex preparation of the present invention, use in the composition, water soluble chitosan comprises one or both or the two or more mixing in water soluble chitin, using carboxyl chitosan, 2-deoxy-D-glucose, chitosan oligosaccharide, chitosan, low molecule, the polymer chitosan etc.; Nucleoprotamine comprises that the chemical composition of Chinese materia medica spermary contains protamine (protamine), deamination nucleotide (deoxynucleotide), arginine (arginine).Pacific herring also contains palmitic acid (palmitic acid), oleic acid (oleic acid), protamine sulfate, sulfuric acid fish gold albumen, and the nucleoprotamine of food-grade, pharmaceutical grade.
A kind of preparation of the present invention is the method for nucleoprotamine complex preparation as mentioned above, it is characterized in that may further comprise the steps:
Accurately take by weighing nucleoprotamine, shitosan, monoglyceride in proportion at aseptic or dust proof workshop, glycine, sodium acetate, acetic acid, put into sterile purified water and fully stir, the aseptic plastic bottle of packing into behind the mixing, glass object, spray container,, in the cillin bottle, plastic sack, paper bag, aerosol bottle.
One, the character of composition is as follows in the present invention's prescription:
1, nucleoprotamine: nucleoprotamine is a kind of polycation peptide that is present in all kinds of fish spermary tissues, has characteristics such as efficient, safe, functional, is a kind of novel natural food preservative that is worth exploitation.
Nucleoprotamine is a kind of basic protein, and mainly the nucleprotamine of conduct and DNA combination exists in fish (as toadfish, crouching fish, catfish etc.) mature sperm cell nucleus.Nucleoprotamine is found in 1870, and between 1940～nineteen sixty, formally the research as antibacterial agent just comes into one's own.Nucleoprotamine demonstrates very strong bacteriostasis in neutral and alkaline medium, and higher heat endurance arranged, heating still had activity in 1 hour under 210 ℃ of conditions, in neutral and alkaline medium, demonstrate very strong bacteriostasis, scope of restraining fungi and food antiseptic scope are all wider simultaneously, it is to hay bacillus, bud bubble bacillus, Lactobacillus casei, lactobacillus plantarum, lactic acid bacteria, mould, bud is embraced thermoduric bacteria and gram-positive bacteria etc. all stronger inhibitory action, it is a kind of natural antimicrobial substance, belong to simple globular protein matter, nontoxic, safe and reliable, degradable antibacterial.
Nineteen forty-two, people such as Miller have studied the bacteriostasis of nucleoprotamine to several gram-positive bacterias and Gram-negative bacteria, found that gram-positive bacteria is responsive especially to nucleoprotamine.Nineteen forty-four, Negroni and Fischer have also obtained same conclusion.The upright people of clock waits the antibiotic property of (1997) research r carp nucleoprotamine, has also verified this conclusion.
Nucleoprotamine is to the growth inhibitory action difference of different strain, so required nucleoprotamine minimum inhibitory concentration is also different different because of bacterial classification.Generally speaking, the minimum inhibitory concentration that nucleoprotamine uses is 100-700mg/kg as the salmon nucleoprotamine to hay bacillus, bacillus licheniformis, the Mlc that solidifies minimums such as bacillus, lactobacillus plantarum, streptococcus fecalis below 1000mg/kg.In addition, in different food, different surrounding medium, the antibacterial minimal effective concentration of nucleoprotamine is also different.
Chemical property:
1), white or off-white powder, odorless has hygroscopicity, and is soluble in water, is insoluble in ethanol, chloroform or the ether.
2), the chemical composition of Chinese materia medica spermary contains protamine (protamine), deamination nucleotide (deoxynucleotide), arginine (arginine).Pacific herring also contains palmitic acid (palmitic acid), oleic acid (oleic acid) etc.
2, shitosan:
Other title of shitosan: claim soluble chitin, chitin, chitose aminoglucose, crust amine, chitosan etc. again, chemistry 2-amino-beta--1 by name, the 4-glucan, chitin be present in unique a kind of band cation of occurring in nature can be by biodegradable distribution macromolecular material extremely widely, be present in a large number in the cell wall of insect, Crustaceans shell and fungi, shitosan is as a kind of Nantural non-toxic, good biocompatibility, degradable, be white or little yellow, colourless, tasteless, unsetting translucent solid or powder.Shitosan is to be raw material with the chitin, forms through refinement again, and is water insoluble, can be dissolved in diluted acid, can be absorbed by the body.
Molecular formula is: (C
6H
11O
4N) n, structural formula is
Water soluble chitosan: Chitosan
Under given conditions; chemical reactions such as hydrolysis, alkylation, acyl groupization, carboxy methylation, sulfonation, nitrated, halogenation, oxidation, reduction, condensation and complexing can take place in chitin and shitosan; can generate various chitin, chitosan derivatives with different performance, thereby enlarge both ranges of application.In the big molecule of chitin and shitosan active hydroxyl and amino are arranged, they have stronger chemical reaction ability.Following reaction can take place in the hydroxyl under alkali condition on the C-6: hydroxyethylation---and chitin and shitosan and oxirane react, and can get hydroxyethylated derivative.Carboxy methylation---chitin and shitosan and chloroacetate reaction just carboxymethylated derivative.Xanthation---chitin is the same with cellulose with shitosan, with generating xanthate acid with the carbon disulphide reaction after the alkaline treatment.Addition reaction can take place in cyanoethylation---acrylonitrile and shitosan, generates the derivative of cyanoethylation.
Above-mentioned being reflected at introduced big side group in chitin and the shitosan, destroyed its crystalline texture, thereby its dissolubility raising, and water soluble, carboxyl methylation derivant demonstrate the character of polyelectrolyte in solution.
Water soluble chitosan comprises chitose aminoglucose, water-soluble chitosan, water-soluble carboxylation shitosan (N-carboxymethyl chitosan, O-CMC), 2-deoxy-D-glucose (2-Deoxy-D-Glucose, 2-DG) its advantage with can in neutral, alkalescence and subacidity water, dissolve, and character is more stable.Shitosan forms through the carboxylation modification, compares with chitin and shitosan, and its physics, chemical property all are optimized, and has water-soluble, film forming and extremely strong heavy metal chelating effect and moisture absorption, preserves moisture, conditioning, function such as antibacterial.The product of this pure natural and totally nontoxic all demonstrates very superior characteristics in fields such as medical health care, industrial or agricultural.(2-Deoxy-D-Glucose is natural antimetabolite class antibiotic 2-DG) to 2-deoxy-D-glucose, has multiple physiological and pharmacological effects such as can suppressing virus infections, culture propagation, pathogenic bacteria and growth of tumour cell.Have effects such as antiviral, antibiotic, anticancer, anti-epileptic, be used for pre-anti-virus and pathogenic bacterial infection etc., can prevent HSV, HIV, SARS, influenza virus etc. and the microbial infectious disease of pathogeny, be with a wide range of applications in industries such as medicine and cosmetics
Purposes: be widely used in fields such as food, feed, medicine, health care, biotechnology.Particularly because the pure natural active of crust amine and having no side effect has good compatibility to human body, its chemical constitution is to have very strong antibiotic property with cationic macromolecule alkalescence polysaccharide polymer, is applied to health food and drug additive energetically.But this both biosynthesis of class polysaccharide is biodegradable again, with organ-tissue and the cell of animal excellent biological compatibility is arranged, and nontoxic, the low molecule oligosaccharide that produces in the degradation process does not accumulate in vivo, almost non-immunogenicity.In its structure, also have active amino, be easy to chemical modification, the natural antibacterial performance is arranged, and has a broad antifungal spectrum.
3, glycine:
Have another name called amion acetic acid, be non-essential amino acid.The title abbreviation: the Gly glycine is that structure is the simplest in the amino acid series, the nonessential seed amino acid of human body, in molecule, have acidity and basic functionality simultaneously, it is strong electrolyte in the aqueous solution, solvability is bigger in intensive polar solvent, substantially be insoluble to non-polar solven, and have higher boiling point and fusing point, the adjusting by aqueous solution Acidity of Aikalinity can make glycine present different molecular conformations.
English name Glycine:Aminoacetic acid
Molecular formula C
2H
5NO
2
Glycine is that existing one of it of both sexes shows acidity-COOH and also has an alkalescence-NH2 equation NH
2CH
2COOH
NaOH+NH
2-CH
2-COOH＝＝NH
2-CH
2-COONa
HCl+NH
2-CH
2-COOH＝＝NH
3Cl-CH
2-COOH
Glycine is mainly used in amino acid injection and does the nutrition transfusion, to can not absorbing (digestive tract function obstacle), long-term deeline through digestive system and being badly in need of supplementing the nutrients with constitutional patient.
Two, nucleoprotamine complex preparation sterilizing mechanisms of the present invention is as follows:
1, can activate the chitinase activity of part microorganism itself, or chitinase is too expressed, cause it to the chitinous degraded of microorganism wall, thus the damaging cells wall.
2, can stop nutriment in microbial cell, to transport, until microbial bacterial death.
3, nucleoprotamine complex preparation of the present invention can damage the integrality of microorganism wall, makes cell wall be tending towards dissolving, until cell death.Biological complex antimicrobials is a kind of suspension energy with strong cation, and bacteria cell wall (especially the gram-positive bacteria cell wall is thicker, structure is tight, contain abundant LTA) negative electrical charge environment of formation, reach the destruction bacteria cell wall thereby form a bioelectricity potential difference, make bacterial cell juice overflow the effect that reaches the kill bacteria cell.
4, the nucleoprotamine complex preparation enters in the microbial cell thoroughly, electronegative cytoplasm in the adherent cell, and flocculation takes place, and upset the normal physiological activity of cell, thus kill bacteria.
Three, carried out a large amount of bactericidal assay research in the nucleoprotamine complex preparation research process of the present invention.Research method mainly requires to carry out according to the relevant sterilizing test of Ministry of Public Health's " disinfection technology standard ".
1, to the killing action (carrier immersion quantitative disinfecting test) of staphylococcus aureus ATCC6538 (representative gram-positive bacteria), stoste proportioning: protamine sulfate (English: reagent grade U.S. sigma, molecular weight: 5000) 0.3g; Water soluble chitosan (water-soluble carboxylation shitosan, carboxylation degree 〉=60%, molecular weight 20,000, the place of production; Zhejiang Province gold shell Biochemie Co., Ltd) 1.9g, glycine (C
2H
5NO
2, molecular weight: the 75.07 pharmaceutical grade places of production: the limited public affairs of the emerging amino acid of Shijiazhuang dan) 1.1g, monoglyceride (food-grade, content 99%, sky, Zhengzhou hundred million chemical products Co., Ltds) 0.5g, sodium acetate (pharmaceutical grade, content 99.7%, the place of production: 0.1g Tianjin Jin Hui chemical reagent Co., Ltd), acetic acid 0.1g (analyze pure by medical grade, content 99.7%, Fanyu, Guangzhou power is strengthened factory), sterile purified water 96ml
Average control bacterium number (cfu/ sheet) 3.01 * 10
4
2, to the killing action (carrier immersion quantitative disinfecting test) of Escherichia coli ATCC8099 (representative Gram-negative bacteria):
Average control bacterium number (cfu/ sheet) 3.01 * 10
4
3, to the killing action (suspension quantitative disinfecting test) of white bacterium ATCC10231 (representative pathogenic fungus):
Average control bacterium number (cfu/ sheet) 2.93 * 10
4
4, to the bactericidal assay at watch face scene
According to code requirement, at experimenter's both hands mutually fully mutually behind the rubbing, sub to its left hand natural bacteria once sampling with the cotton examination of having soaked into sample solution, the examination unginned cotton spends to put in the 10ml sample solution and organizes in contrast, use the medicine liquid spray both hands, to the natural bacteria once sampling of experimenter's right hand, as the experimental group sample, carry out the viable bacteria radix after 1 minute.Test repeats 30 times.All more than 98%, average kill ratio is 99.2% to the test of each time as a result to watch face nature killing rate.
5, organic influence:
Carrier soaks quantitative disinfecting test and shows, 25% and 50% calf serum with produce mouthful 1/3 dilution, effect 21min reaches 99.94% to the killing rate that contains 25% calf serum gold Portugal bacterium; Effect 28min reaches 99.96 to the killing rate that contains 50% calf serum gold Portugal bacterium.Show that in the presence of large amount of organic nucleoprotamine complex preparation of the present invention still shows powerful bactericidal action.
Four, nucleoprotamine complex preparation of the present invention has been undertaken acutely advancing through product toxicity test, skin irritatin test, eye irritant test, vaginal mucomembranous irritant test, cumulative toxicity test and PCEMNR micronucleus test by the requirement of Ministry of Public Health's " disinfection technology standard ".
One, acute toxicity (per os LD
50) test:
Purpose: sample contacts the health hazard that can cause and obtains half lethal dose by a per os, for acute classification, classification provide according to (for inferior chronic experiment and other experiments determine that dosage provides reference).
1, sample proterties: transparency liquid, water-soluble
2, sample treatment and configuration: sample thief 5500mg adding distil water 20ml
3, laboratory animal: NIH mouse (animal quality certification 2002A0365 number), 18-22g
4, experimental technique: by " disinfection technology standard " test.
4.1 before the experiment, laboratory animal fasting 16 hours.
4.2 with the animal random packet, each one group of male and female, 10 every group, weigh, press the 0.4ml/20g body weight, adopt administration by gavage to give a sample.
4.3 observe to two weeks behind the sample, the poisoning manifestations of laboratory animal and death condition.
4.4 calculate LD
50And 95% credibility interval.
5, result:
Table male and female chmice acute per os toxicity test result
6, conclusion: female mice: LD
50＞5000mg/kg
Male mice: LD
50＞5000mg/kg
Per os carries out toxicity LD
50＞5000mg/kg, the nontoxic level in true border
Two, cumulative toxicity test
Cumulative toxicity test: NIH mouse (animal quality certification 2002A035 number) 18-22g, mouse gastric infusion every day.
Three, acute eye irritation test
New zealand rabbit (quality certification 99A031 number), about 2kg, every rabbit one ocular administration, a glance contrast.
Four, vaginal mucomembranous irritant test: SD rat (quality certification 99A032), about 250g
Five, mouse bone polychromatic erythrocyte micronucleus test:
Kunming mice (quality certification 99A029), 25-30g establishes physiological saline negative control group, cyclophosphamide (40mg/kg) positive controls and experimental group.
Six, measure the nucleoprotamine complex preparation to mouse burn wound staphylococcus aureus killing effect
1, method
(1), infection of burn model:
Animal is Kunming kind small white mouse, male and female half and half, body weight 25-30g.Animal is divided into three groups at random, causes mouse back skin I II degree burn (75 ℃, 15 seconds), burn surface area (about 5cm with the circular flatiron of diameter 2.6cm
2) account for the 6-7% of mouse corpus surface area, to hinder back 30 minutes, surface of a wound inoculum density is the staphylococcus aureus bacterium liquid 0.1ml of 109cfu/ml, bacterial strain is staphylococcus aureus ATCC25923.
(2), burn wound disinfects
Behind burn wound inoculation staphylococcus aureus 3-4 hour, pick the physiological saline that contains 0.02% lauryl sodium sulfate with aseptic cotton swab, embrocate the surface of a wound and do sampling before the sterilization, use the nucleoprotamine complex preparation then, the burn wound of applying ointment or plaster (1-2ml/).Disinfective action 30 minutes remakes the sterilization post-sampling.Through the vibration washing, sampling liquid 0.1ml smears the agar plate inoculation, and 2 flat boards of each sample liquid inoculation were cultivated 48 hours in 37 ℃ of incubators, observed final result.
2, result
The result proves through nucleoprotamine complex preparation sterilization 24 hours, do not have staphylococcus aureus to detect, and 19 mouse of control group then all have staphylococcus aureus to detect.
Biological complex antimicrobials is to burn wound staphylococcus aureus Disinfection Effect
| Group | Detect number of animals (only) | Positive number of animals (only) | Positive rate (%) |
| The nucleoprotamine complex preparation | 24 | 0 | 0 |
| Control group | 19 | 19 | 100.00 |
After the sterilization of nucleoprotamine complex preparation, there is not staphylococcus aureus to detect.Prove that through 24 artificial burned mice simulation sterilizing tests the nucleoprotamine complex preparation has killing action to the staphylococcus aureus of artificial contamination's burn wound.
Seven, the nucleoprotamine complex preparation is to the mensuration of the practical Disinfection Effect of human body burn wound Staphylococcus aureus
1, method
(1), the preparation of nucleoprotamine complex preparation, accurately claim protamine sulfate (English: reagent grade U.S. sigma, molecular weight: 5000) 0.2g; Water soluble chitosan (water soluble chitosan (water-soluble carboxylation shitosan, carboxylation degree 〉=60%, molecular weight 20,000, the place of production; Zhejiang Province gold shell Biochemie Co., Ltd) 1.9g, glycine (C
2H
5NO
2, molecular weight: the 75.07 pharmaceutical grade places of production: the limited public affairs of the emerging amino acid of Shijiazhuang dan) 1.2g, monoglyceride (food-grade, content 99%, sky, Zhengzhou hundred million chemical products Co., Ltds) 0.5g, sodium acetate (pharmaceutical grade, content 99.7%, the place of production: 0.1g Tianjin Jin Hui chemical reagent Co., Ltd), 0.1g, acetic acid 0.1g (medical grade, content 99.7%, analyze purely, Fanyu, Guangzhou power is strengthened factory) put into sterile purified water 96ml and fully stir and get final product.
(2), practical sterilizing test
Test is got 2ml with the nucleoprotamine complex preparation, and used neutralizer is the physiological saline that contains 0.02% lauryl sodium sulfate.Before the sterilization, soak in the test tube that contains neutralizer physiological saline with aseptic cotton swab, and after inboard wall of test tube is extracted, embrocate sampling in the sample region that patient's burn wound delimited, sampling area is 1cm
2, after the sampling, cotton swab is put back to former sample solution in vitro, as contrast before the sterilization.During sterilization, with the nucleoprotamine complex preparation of the 2m1 patient's burn wound of applying ointment or plaster, after the disinfective action 2 hours, do the sterilization sampling, sample solution is through beaing washing, the sampling liquid stoste or suitably dilute after, make high salt mannite agar and pour into inoculation, every ware 0.1ml, duplicate, put and cultivate 48h in 37 ℃ of incubators, observe final result.
2, result
Prove that with the practical sterilizing test of 11 routine fire victims through the nucleoprotamine complex preparation was applied ointment or plaster sterilization to burn wound after, surface of a wound staphylococcus aureus number was by 1850-55650cfu/cm
2Drop to 0-2250cfu/cm
2, the killing rate scope is 91.66-100.00%.Killing rate to the staphylococcus aureus of patient's burn wound reaches more than 98.00%, and nucleoprotamine complex preparation disinfectant has good killing effect at the infection of staphylococcus aureus that burn causes.
3, the infection of burn wound:
Infection of burn accounts for the first place of the burn cause of death always, also is the principal element that influences wound healing.This product is used for 1000 many cases burn patients clinically, comprising the degree of depth and large-area burns patient, liked by medical personnel and patient, generally reaction control infection speed is fast, effective, nonirritant, easy to use, and can effectively promote the dry incrustation of the surface of a wound, none routine bad reaction report can effectively prevent the generation of burn wound sepsis and burn septicemia.
This product belongs to liquid preparation, and permeability is strong, and it is little that bactericidal effect is disturbed by organic matter, also effective to the purulence blood surface of a wound, can be when debridement usefulness, after the debridement with and be used for the daily anti-inflammatory nursing of wound.
| Common antibiotics | Common disinfectants | Biological composite disinfectant | |
| Antimicrobial spectrum | Limited | Extensively | Extensively |
| Excitant | Do not have | Greatly | Do not have |
| Pesticide resistance | Have | Do not have | Do not have |
| Organic matter disturbs | Do not have | Greatly | Do not have |
| Onset speed | Slowly | Slowly | Hurry up |
| Promote the dry incrustation effect of the surface of a wound | Do not have | Do not have | Obviously |
| Toxicity | Low | Greatly | Low |
Nucleoprotamine complex preparation fungicidal spectrum of the present invention is wide, common germ to infection of burn has quick and powerful killing action, as golden Portugal bacterium, Pseudomonas aeruginosa, the Fu Shi bacillus citrate, other enteron aisle negative bacillus of nitrate-negative bacillus etc. comprise all bacterial propagules in theory to the bacterium of this product sensitivity.
Nucleoprotamine complex preparation of the present invention does not have the pesticide resistance problem, nontoxic nonirritant, and the daily anti-inflammatory that especially is suitable for the longer course for the treatment of of large-area burns is nursed.
Compared with prior art, effect intentionally of the present invention:
The Main Ingredients and Appearance of nucleoprotamine complex preparation of the present invention is nucleoprotamine, water soluble chitosan, glycine, sodium acetate, acetic acid, monoglyceride, can not produce stimulation to skin and mucous membrane, body is not produced any toxic and side effect, and can thoroughly degrade by metabolism, do not have residually, do not influence environmental protection.Its advantage is as follows:
1) wholesomeness.The nucleoprotamine complex preparation is being killed aspect the antibiotic-resistant coccus, demonstrates unique effect.Bactericidal effect is splendid.
2) fungicidal spectrum is wider.Nucleoprotamine complex preparation oral spray can not only be killed methicillin-resistant staphylococcus aureus, and can effectively kill common malignant bacterias such as Escherichia coli, Candida albicans, hemolytic streptococcus, anaerobic bacteria, Pseudomonas aeruginosa.
3) bactericidal activity and stability are much higher than any monoprotamine or shitosan.Because the nucleoprotamine complex preparation is to be main component with nucleoprotamine, shitosan, being equipped with effective biotic component such as stabilizing agent, synergist is composited, stable in temperature active maintenance below 80, PH accommodation 3-14, solution preserve 3 years activity and still keep stable.
Nucleoprotamine complex preparation of the present invention is effective especially to the gram-positive bacteria sense gram positive bacterial infection coccus of the cross-infection in the hospital, burn and operation patients, and other disinfectants and medicine can't be mentioned in the same breath with it.
At present, the nosocomial infection of drug resistance coccus MRSA is very extensive, and bacterium has pesticide resistance to the most antibiotics except vancomycin.But the vancomycin toxic and side effect is very big, and after patient used, the liver renal toxicity was big.In addition, vancomycin can not external application, the clinical SD-Ag commonly used of I and wash must be safe strong to the damaged skin excitant, to MRSA do not have substantially effect and also recently existing people report the drug resistance staphylococcus aureus of finding anti-vancocin.So external preparation that clinical especially burn urgent need can be killed the drug resistance staphylococcus aureus.Zhongshan city's health is the nucleoprotamine complex preparation hydrolysis gram-positive bacteria drug resistance staphylococcus aureus particularly of glad biologic medical Science and Technology Ltd. development and production, thereby thorough killing bacteria, be difficult for producing endurance strain, there is not any skin irritation again, so these product are a kind of very promising skin disinfectant for external use.
The surface of a wound of MRSA infection is the residual wound in late period of healing difficulty mostly clinically, and secretion obviously reduces behind the external application nucleoprotamine complex preparation of the present invention, and the surface of a wound begins healing.After continuous three uses, most surface of a wound MRSA turn out cloudy, and total sterilizing rate reaches more than 98%, promotes wound healing, reduces cross infection in hospital.
Nucleoprotamine complex preparation bactericidal activity of the present invention is strong, reaches the purpose of dissolving and killing bacteria, and can avoid the generation of bacterial drug resistance.Nucleoprotamine complex preparation energy hydrolysis Gram-positive bacteria cell wall of the present invention, thus thorough killing bacteria has been avoided the generation of bacterial drug resistance.Carry out raw fish extract albumen complex preparation by the bacterium of strain more than 200 of collecting and pressed down sterilization experiment.Experimental result shows: the nucleoprotamine complex preparation is to gram-positive bacteria; As common clinically staphylococcus aureus, Staphylococcus epidermidis, Diplococcus pneumopniae, D group enterococcus, tetrads, product monokaryon Listeria, streptococcus and stomach Helicobacter pylori etc. all have tangible inhibitory or killing effect.
This series nucleoprotamine complex preparation is easy to make, this specification provides and various product, be applicable to various formulations, said preparation can make an addition to external application medicine (skin, skin and mucosa), oral drugs, ear medicine, nose medicine, vitamins, daily use chemicals, can be made into aerosol, aqueous solvent, granule, spray, patch, liniment, a kind of in the mouth spraying agent.
The mouth disease that the medicine that has added nucleoprotamine complex preparation of the present invention can be used for treating abscess, psoriasis, ulcer, bedsore, scalds, burns, furuncle, canker sore, incised wound, vaginitis, each bacterial infection cause, respiratory disease, acute or chronic gastritis, all kinds of tympanitis, keratitis, conjunctivitis, sty, utmost point rhinitis chronic, nasosinusitis, prevention of STD, prevent and treat acne, all kinds of by bacterium, fungus-caused skin of face illness etc.; Debridement and the wound dressing that can also be used for various operation preoperative and postoperatives such as surgery, urological department, the department of stomatology, department of obstetrics and gynecology, ear-nose-throat department; Can be used for disinfections such as various surgical apparatuses, endoscope, surgical knife tool, conduit.
Nucleoprotamine complex preparation preparation method of the present invention is simple, benefits large-scale production.
Embodiment
According to different press down, sterilization requires and easy to use, but concrete configuration becomes: one: be configured to water white transparency nucleoprotamine complex preparation.
Embodiment 1
Nucleoprotamine complex preparation of the present invention is made up of the content of following percentage by weight:
Proportioning:
Method: in desinfection chamber or superclean bench, with the weighing accurately of above reagent, nucleoprotamine 0.3g, water soluble chitosan 1.9g, glycine 1.1g, monoglyceride 0.5g, sodium acetate 0.1g, acetic acid 0.1g, sterile purified water 96ml (96g), put into clean glass or stainless steel container, stir gently, after fully mixing, be encapsulated into and get final product in the sterile chamber.
Use: this proportioning can be used for making the skin and mucosa disinfection sanitizer, can kill staphylococcus aureus, Candida albicans, the Escherichia coli of skin, mucous membrane surface in 2-10 minute, and killing rate reaches 99.8%.The mouth disease, the prevention of STD that can treat abscess, psoriasis, ulcer, bedsore, scald, burn, furuncle, canker sore, incised wound, vaginitis, each bacterial infection cause are used for debridement and the wound dressing of various operation preoperative and postoperatives such as surgery, urological department, the department of stomatology, department of obstetrics and gynecology, ear-nose-throat department.
Embodiment 2
Nucleoprotamine complex preparation of the present invention is made up of the content of following percentage by weight:
Proportioning:
Method: glass or the stainless steel container of in desinfection chamber or superclean bench, 10g acetic acid being put into cleaning, add sterile purified water 67ml, stir gently, after fully mixing, add again, after the 10g water soluble chitosan was mixed, adding 0.01g nucleoprotamine, 10g glycine, 0.1g monoglyceride, 2.89g sodium acetate fully mixed, and were encapsulated in the sterile chamber to get final product.
Embodiment 3
Nucleoprotamine complex preparation of the present invention is made up of the content of following percentage by weight:
Proportioning:
Method: make in its even aseptic carrier fluid vessel of packing into that are mixed packaged as above-mentioned 1 and 2 one sample loading mode.
Embodiment 4
Nucleoprotamine complex preparation of the present invention is made up of the content of following percentage by weight:
Proportioning:
Nucleoprotamine 10%
Water soluble chitosan 0.01%
Sterile purified water 89.99%
Method: in desinfection chamber or superclean bench, above composition is put into clean glass or stainless steel container, stir gently, after fully mixing, pour into encapsulation in the sterile chamber.
Embodiment 5
Proportioning:
Nucleoprotamine 10%
Water soluble chitosan 10%
Sterile purified water 80%
Method: in desinfection chamber or superclean bench with above measure composition put into clean glass or stainless steel container, stir gently, after fully mixing, pour into encapsulation in the sterile chamber.
Embodiment 6
Proportioning:
Nucleoprotamine 0.01%
Water soluble chitosan 10%
Sterile purified water 89.99%
Method: in desinfection chamber or superclean bench, the reagent of above amount is put into clean glass or stainless steel container, stir gently, after fully mixing, pour into encapsulation in the sterile chamber.
The mouth disease that above nucleoprotamine complex preparation is mainly used in treating abscess, psoriasis, ulcer, bedsore, scalds, burns, furuncle, canker sore, incised wound, vaginitis, each bacterial infection cause, respiratory disease, acute or chronic gastritis, all kinds of tympanitis, keratitis, conjunctivitis, sty, utmost point rhinitis chronic, nasosinusitis, prevention of STD, prevent and treat acne, all kinds of by bacterium, fungus-caused skin of face illness etc.; Debridement and the wound dressing that can also be used for various operation preoperative and postoperatives such as surgery, urological department, the department of stomatology, department of obstetrics and gynecology, ear-nose-throat department; Can be used for disinfections such as various surgical apparatuses, endoscope, surgical knife tool, conduit.
Two: be configured to biological composite antibiosis pulvis
Embodiment 7
Proportioning:
Nucleoprotamine 99.99%
Water soluble chitosan 0.01%.
Method: in desinfection chamber or superclean bench, nucleoprotamine and water soluble chitosan are put into clean glass or stainless steel container, stir gently, after fully mixing, be encapsulated in aseptic cillin bottle or north material bottle or the plastic sack and get final product.
Embodiment 8
Proportioning:
Milt egg 50%
Water soluble chitosan 50%.
Method: as above the operation of the method for embodiment 7 is mixed, and is encapsulated in the container.
Embodiment 9
Proportioning:
Nucleoprotamine 0.01%
Water soluble chitosan 99.99%
Method: as above the operation of the method for embodiment 7 is mixed, and is encapsulated in the container.
Embodiment 10
Proportioning:
Method: in desinfection chamber or superclean bench, by above amount nucleoprotamine, water soluble chitosan, glycine, sodium acetate, monoglyceride are put into clean glass or stainless steel container, stir gently, after fully mixing, be encapsulated in aseptic cillin bottle or north material bottle or the plastic sack and get final product.
Embodiment 11
Proportioning:
Method: by with the preparation method among the embodiment 10, it is mixed, is encapsulated in aseptic cillin bottle or north material bottle or the plastic sack and gets final product.
Embodiment 12
Proportioning:
Method: the as above method of embodiment 7, it is mixed, be encapsulated in aseptic cillin bottle or north material bottle or the plastic sack and get final product.
The wound debridement wrapping of difficult contact water such as above nucleoprotamine complex preparation is mainly used in burning, scalds, serious canker sore, skin and mucosa infection can also be used for debridement and the wound dressing of various operation preoperative and postoperatives such as surgery, urological department, the department of stomatology, department of obstetrics and gynecology, ear-nose-throat department.
Embodiment 13
Proportioning:
In desinfection chamber or superclean bench, by above amount above-mentioned substance is put into clean glass or stainless steel container, stir gently, after fully mixing, be encapsulated in aseptic cillin bottle or north material bottle or the plastic sack and get final product.
Embodiment 14
Proportioning:
In desinfection chamber or superclean bench, by above amount above-mentioned substance is put into clean glass or stainless steel container, stir gently, after fully mixing, be encapsulated in aseptic cillin bottle or north material bottle or the plastic sack and get final product.
Embodiment 15
Proportioning:
In desinfection chamber or superclean bench, by above amount above-mentioned substance is put into clean glass or stainless steel container, stir gently, after fully mixing, be encapsulated in aseptic cillin bottle or north material bottle or the plastic sack and get final product.
Claims (4)
1. nucleoprotamine complex preparation is characterized in that composed of the following components by weight percentage:
2. nucleoprotamine complex preparation according to claim 1 is characterized in that described nucleoprotamine complex preparation can be made into pulvis, aqueous solvent, gel, capsule, granule, spray, patch, liniment, a kind of in the mouth spraying agent.
3. method for preparing claim 1 or 2 described nucleoprotamine complex preparations is characterized in that may further comprise the steps:
Accurately take by weighing each component in proportion at aseptic or dust proof workshop, put into clean glass or the stainless steel container stirs, be encapsulated in the sterile chamber, get final product.
4. claim 1 or 2 described nucleoprotamine complex preparations are being used in external application medicine, oral drugs, ear medicine, nose medicine, vitamins, daily use chemicals, health food.
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| CN114651819A (en) * | 2022-03-10 | 2022-06-24 | 上海芜玮建晖生物科技有限公司 | Organic disinfectant based on marine resources |
| CN114668006A (en) * | 2022-04-19 | 2022-06-28 | 陕西康禾立丰生物科技药业有限公司 | Biological disinfectant based on natural tartaric acid and preparation process thereof |
| CN115152793A (en) * | 2022-07-25 | 2022-10-11 | 独春堂生物科技研究院(菏泽)有限公司 | Purifying agent for ICU ward purification and preparation method thereof |
| CN115369061A (en) * | 2022-08-24 | 2022-11-22 | 山东博科生物产业有限公司 | Selective helicobacter pylori culture medium and preparation method thereof |
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| 于化泓等.动物中的抗菌防腐剂.《江西食品工业》.2004,(第01期),38-39. |
| 动物中的抗菌防腐剂;于化泓等;《江西食品工业》;20040330(第01期);38-39 * |
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