CN114028546A - Composite polypeptide sterilization preparation and preparation method and application thereof - Google Patents

Composite polypeptide sterilization preparation and preparation method and application thereof Download PDF

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CN114028546A
CN114028546A CN202111462334.7A CN202111462334A CN114028546A CN 114028546 A CN114028546 A CN 114028546A CN 202111462334 A CN202111462334 A CN 202111462334A CN 114028546 A CN114028546 A CN 114028546A
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parts
polypeptide
preparation
sterilization
composite polypeptide
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杨凤才
陈会军
鞠方涛
崔满春
张斌
石秀芳
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Beijing Xidebao Sterilizing Products Co ltd
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Beijing Xidebao Sterilizing Products Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46Hydrolases (3)
    • A61K38/47Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/19Acanthaceae (Acanthus family)
    • A61K36/195Strobilanthes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/31Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
    • A61K36/315Isatis, e.g. Dyer's woad
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/35Caprifoliaceae (Honeysuckle family)
    • A61K36/355Lonicera (honeysuckle)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/164Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1767Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/02Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/04Antipruritics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02Local antiseptics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10Antimycotics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses

Abstract

The invention discloses a composite polypeptide sterilization preparation, which comprises natural biological components and traditional Chinese medicine components, wherein the natural biological components comprise: 0.1-10 parts of antibacterial peptide, 0.01-1 part of melittin and 0.2-1 part of biological lysozyme, and the traditional Chinese medicine components comprise 0.1-2 parts of honeysuckle and 0.1-2 parts of isatis root. The invention also discloses a preparation method of the compound polypeptide sterilization preparation, which comprises the following steps: 0.1-10 parts of antibacterial peptide, 0.01-1 part of melittin and 0.2-1 part of biological lysozyme are sequentially added into 83-99.39 parts of pH buffer solution, then 0.1-2 parts of honeysuckle and 0.1-2 parts of isatis root are added, and the composite polypeptide sterilization preparation is obtained through emulsification and stirring. The invention has different degrees of bacteriostasis to various pathogenic bacteria, effectively improves the effects of sterilization, bacteriostasis, anti-inflammation and anti-allergy, improves the sterilization effect and is convenient to use.

Description

Composite polypeptide sterilization preparation and preparation method and application thereof
Technical Field
The invention belongs to the technical field of sterilization preparations, and relates to a composite polypeptide sterilization preparation, and a preparation method and application thereof.
Background
At present, for the prevention and control of new crown epidemic situation, a disinfectant and an antibacterial agent are important links for the prevention and control of the new crown epidemic situation and are very important for blocking indirect transmission. But the no-wash hand disinfectant and the bactericide in the market have certain benefits on daily disinfection and virus prevention, but the long-term use of the bactericide can also cause harm to human bodies:
1. at present, the no-clean quick hand sanitizer and the bactericide in the market contain surfactant, fluoride, strontium chloride, alcohol, water and the like, can remain on the skin, and some substances are harmful to the body, such as the surfactant, the fluoride, the essence and the like. These products develop resistance to drugs and even allergic reactions over long periods of time.
2. Most of disinfectants and bactericides on the market belong to chemical component products such as biguanides, quaternary ammonium salts, triclosan and ethanol, and many disinfectants and bactericides contain plasticizers and zinc, but excessive use of the products can generate certain toxicity and irritation and adhere to skin mucous membranes of people, so that uncomfortable symptoms such as redness and swelling, burning pain, skin chap and the like are caused. Zinc also enters intestines and stomach from oral cavity, and further induces symptoms such as stomachache, regurgitation, nausea and the like.
3. And a part of disinfectants and bactericides mainly comprise chemical compounds with strong oxidizing property, such as sodium hypochlorite, hydrogen peroxide and the like, the strong oxidizing property plays a role in sterilization and disinfection, and the disinfectants and the bactericides have certain corrosivity and volatility, and when the cleaning products are evaporated, a large amount of harmful gas can be accumulated indoors. After being inhaled by people, the Chinese herbal medicine has strong stimulation effect on respiratory mucosa, particularly, dichlorobenzene is contained, and the long-term inhalation can stimulate the respiratory system to cause system damage.
4. During epidemic situations, hypochlorous acid disinfectant is on the market, the component of hypochlorous acid is effective, but the composition profile does not represent the performance of products obtained by consumers, the good effect can be achieved for a long time, and the stability of hypochlorous acid products is difficult to achieve. In conclusion, the chemical disinfectant has the characteristics of various varieties, quick response, convenient use, low price and the like, and therefore, the chemical disinfectant has a leading position in the disinfection market. However, due to the unreasonable use of chemical disinfectants by human beings and inherent disadvantages, the chemical disinfectants cause many problems in use, such as environmental pollution, metal corrosion, poisoning of human and livestock, residue and the like. In particular, the medium-effect disinfectant and the low-effect disinfectant have wide application range, and relate to various industries, families and crowds besides medical institutions. Through the above analysis, the problems and defects of the prior art are as follows:
(1) at present, some substances contained in the no-clean quick hand sanitizer on the market are harmful to human bodies, can generate drug resistance after long-term use, even can cause anaphylactic reaction, and are not beneficial to human health.
(2) The existing disinfectants and bactericides generate certain toxicity and irritation when being used excessively and are attached to skin mucous membranes, so that discomfort symptoms such as redness and swelling, burning pain, skin chapping and the like are caused; zinc can enter intestines and stomach from oral cavity, and further induce symptoms such as stomachache, regurgitation, nausea and the like; the hand-washing-free disinfectant and bactericide using industrial alcohol also contain methanol, and are inhaled by breathing or absorbed through skin, so that the risk of damaging the health of a human body exists.
(3) The existing disinfectants and bactericides composed of chemical compounds with strong oxidizing property have certain corrosivity and volatility, when cleaning products are evaporated, a large amount of harmful gas can be accumulated indoors, and the disinfectants and the bactericides have strong stimulation effect on respiratory mucosa after being inhaled by people, particularly the existing disinfectants and bactericides containing dichlorobenzene can stimulate the respiratory tract after being inhaled for a long time and induce cell variation to cause leukemia, lung cancer and the like; the stability of the existing hypochlorous acid disinfectant does not reach the standard.
With the improvement of the quality of life and the enhancement of environmental awareness of people, the development of a biological disinfectant which is safe to people and animals, free of pollution, low in toxicity and free of residues is an urgent problem. Today of the rapid development of economy, people's standard of living has not only been in the fact that it is full to wear warm far away, and daily disinfection safety and health problem receive more and more attention of people, and green healthy life also becomes everybody's common pursuit, and along with the development of science and technology, people pay more and more attention to security, the feature of environmental protection of disinfectant, germicide, and the kind and the quantity of use of chemical disinfectant have gradually declined. Therefore, the development and application of natural biological bactericides and Chinese herbal medicine compound disinfectants have become a general trend in the field of disinfection in the world. Natural biological and plant extracts are widely used in the medical and health disinfection industry due to their own characteristics, and it is the focus of research on how to develop a disinfectant suitable for medical and health disinfection and civil use mainly from natural biological and plant extracts. Therefore, an improved technique for solving the problem in the prior art is desired.
Disclosure of Invention
An object of the present invention is to solve at least the above problems and/or disadvantages and to provide at least the advantages described hereinafter.
The invention also aims to provide a composite polypeptide sterilization preparation.
The invention also aims to provide a preparation method of the composite polypeptide sterilization preparation.
The invention also aims to provide the application of the compound polypeptide bactericidal preparation in killing pathogenic bacteria and preparing anti-inflammatory and antibacterial medicaments.
Therefore, the technical scheme provided by the invention is as follows:
the compound polypeptide sterilization preparation comprises natural biological components and traditional Chinese medicine components, wherein the natural biological components comprise the following components in parts by weight: 0.1-10 parts of antibacterial peptide, 0.01-1 part of melittin and 0.2-1 part of biological lysozyme, wherein the traditional Chinese medicine components comprise 0.1-2 parts of honeysuckle and 0.1-2 parts of isatis root. Preferably, honeysuckle and isatis root adopt respective corresponding traditional Chinese medicine extracts.
Preferably, in the composite polypeptide bactericidal preparation, the natural biological components further include:
0.1-1 part of natamycin and 83-99.39 parts of pH buffer solution.
Preferably, the composite polypeptide sterilization preparation further comprises:
the hydrogel component comprises 1-5 parts of sodium hyaluronate, 0.01-0.5 part of fucoidin, 1-5 parts of chitosan, 0.1-0.6 part of glacial acetic acid and 0.04-0.1 part of towel gourd iron.
Preferably, in the composite polypeptide bactericidal preparation, the antibacterial peptide is nisin or spirulina polypeptide or a mixture of nisin and spirulina polypeptide in a mass ratio of 1: 1.
The preparation method of the compound polypeptide sterilization preparation comprises the following steps:
according to parts by weight, 0.1-10 parts of antibacterial peptide, 0.01-1 part of melittin and 0.2-1 part of biological lysozyme are sequentially added into 83-99.39 parts of pH buffer solution and mixed evenly, then 0.1-2 parts of honeysuckle and 0.1-2 parts of radix isatidis are added, and the mixture is emulsified and stirred for about 30 minutes to obtain the composite polypeptide sterilization preparation. Preferably, honeysuckle and isatis root adopt respective corresponding traditional Chinese medicine extracts.
Preferably, in the preparation method of the composite polypeptide sterilization preparation, 0.1-1 part of natamycin is added into the composite polypeptide sterilization preparation.
Preferably, the preparation method of the composite polypeptide sterilization preparation further comprises the following steps:
sequentially adding 0.1-0.6 part by weight of glacial acetic acid, 1-5 parts by weight of chitosan and 0.04-0.1 part by weight of towel gourd iron into water, uniformly stirring, standing for 12 hours, and freeze-drying to obtain a chitosan and towel gourd vegetable sponge compound;
and adding the chitosan and loofah sponge compound into the composite polypeptide sterilization preparation and sterilizing.
Preferably, in the preparation method of the composite polypeptide sterilization preparation, the pH buffer solution is phosphate buffered saline solution.
Preferably, in the preparation method of the composite polypeptide bactericidal preparation, the antibacterial peptide is nisin or spirulina polypeptide or a mixture of nisin and spirulina polypeptide in a mass ratio of 1: 1.
The compound polypeptide bactericidal preparation is used for killing pathogenic bacteria and preparing anti-inflammatory and antibacterial medicaments. .
The invention at least comprises the following beneficial effects:
the composite polypeptide sterilization preparation provided by the invention can effectively kill pathogenic bacteria such as escherichia coli, staphylococcus aureus, helicobacter pylori, coronavirus, oral bacteria and the like, has the effects of resisting bacteria, viruses, tumors, hemostasis, detumescence, relieving pain, accelerating tissue recovery function, repairing cells, improving cell metabolism, preventing cell degeneration and the like, can be used for treating diseases such as wound, wiping, falling wound, incised wound, inflammation diminishing, fungal infection and promoting wound healing and preventing diseases such as ear eczema, breast eczema, scrotum eczema, hand eczema, perianal eczema, shank eczema and the like, can help solve the discomfort caused by skin itching, dryness, desquamation, pruritus, dermatitis, blisters and the like of various parts of the body, and has no harm to the health of the human body.
The invention takes antibacterial peptide, melittin, biological lysozyme and natamycin with different concentration ratios as main components, and adds the traditional Chinese medicine components of honeysuckle and isatis root to prepare the compound polypeptide antibacterial agent. The composite polypeptide antibacterial agent has no harm and side effect to human health, can kill pathogenic bacteria such as colibacillus, staphylococcus aureus, helicobacter pylori and the like, oral bacteria and pathogenic bacteria, has core components of biological antibacterial peptide, melittin and biological lysozyme, is an active amino acid chain with high content, is an intermediate product for degrading protein into amino acid, and has unique physiological activity and medical health care function which are not possessed by original protein and monomer amino acid. It is used in antibacterial preparation, health promotion and medical treatment, and has effects of killing pathogenic bacteria, removing odor (halitosis, bromhidrosis, and bromhidrosis), promoting tissue recovery, repairing cells, improving cell metabolism, and preventing cell degeneration. It is also an important "antibacterial molecule" when applied to the skin mucosa, which can dissolve the bacterial cell wall and thus dissolve the bacteria, in short, it is a "protective layer" that directly penetrates the outside of the bacteria, and goes deep into the interior of the enemy, thus killing the bacteria.
People in modern society have increasingly strengthened awareness of daily disinfection safety and health care of health problems, and some families have brought antibacterial agents into one of daily necessities. Compared with the common antibacterial agents and therapeutic antibacterial agents on the market, the composite polypeptide antibacterial agent has the effects of killing escherichia coli, staphylococcus aureus, helicobacter pylori, oral bacteria and human coronavirus, accelerating the tissue recovery function, promoting wound healing, repairing cells, improving cell metabolism, preventing cell degeneration and the like, has no harm to a human body, kills and inhibits the bacteria through biological antibacterial peptide, melittin and biological lysozyme, does not generate drug resistance, has no side effect, is safer, and can be used by pregnant women and children. Meanwhile, the hand eczema cream can prevent diseases such as hand eczema, face eczema, ear eczema, breast eczema, scrotum eczema, perianal eczema, shank eczema and the like, can help solve the discomfort caused by skin redness and itching, dryness, desquamation, pruritus, dermatitis blisters and the like which are puzzled by skins of various parts of a body, and has no harm to human health. And has antiinflammatory, antibacterial, anticancer, radioprotective, platelet aggregation inhibiting, skin protecting and skin pathological reaction preventing effects.
The polypeptide antibacterial agent has obvious effective killing and inhibiting effects on escherichia coli, staphylococcus aureus, helicobacter pylori and coronavirus on hands and skin mucous membranes, has good antibacterial effects on streptococcus group A, anaerobic streptococcus, staphylococcus epidermidis, Neisseria (Neisseria), Lactobacillus (Lactobacillus), spirochete (Spirochaeta), Candida (Candida) and the like which often exist in oral cavities, eliminates pathogenic microorganisms outside human bodies, cuts off the transmission path of infectious diseases, achieves the aim of controlling the infectious diseases, prevents the pathogenic microorganisms from entering the respiratory tracts of the human bodies, reduces the morbidity risk and prevents the diseases. The product has good stability, strong antibacterial activity and broad-spectrum bactericidal action, and can be used as substitute of the existing chemical disinfectants, bactericides, skin repair liquid and skin mucosa disinfectant. The composite polypeptide antibacterial agent is not only used for treating skin mucosa diseases, but also can prevent oral diseases such as human oral gingivitis, glossitis, oral ulcer, dental calculus, halitosis and the like, and has the functions of oral deodorization, antibiosis, anti-inflammation and antianaphylaxis.
Nisin (Nisin), also known as Nisin or transliteration as nixin, is a polypeptide substance produced by streptococcus lactis and consists of 34 amino acid residues with a molecular weight of about 3500 Da. Since nisin inhibits most gram-positive bacteria and strongly inhibits spores of bacillus, nisin is widely used in the food industry as a food preservative. After being eaten, the edible fungus is quickly hydrolyzed into amino acid under the physiological pH condition of a human body and the action of alpha-chymotrypsin, so that the normal flora in the intestinal tract of the human body can not be changed, the resistance problem of other antibiotics can not be generated, and the edible fungus can not be mixed with other antibiotics. Because nisin is a polypeptide and is easily decomposed by plant protease after entering a human body, the nisin is a safe and nontoxic natural food preservative. The nisin has extremely high stability, can be digested and absorbed by human bodies, can not generate cross resistance with other antibiotics, and is a natural food preservative with natural, green, high efficiency, no toxicity, safety and no side effect and excellent safety. The streptococcus lactis is a living live bacterium, the nisin is a metabolite secreted in the metabolic process and has an antibacterial effect, and the nisin is a medicament, is a biological agent and does not have side effects like antibiotics or side effects for promoting drug resistance of germs like the antibiotics.
Additional advantages, objects, and features of the invention will be set forth in part in the description which follows and in part will become apparent to those having ordinary skill in the art upon examination of the following or may be learned from practice of the invention.
Drawings
Fig. 1 is a flowchart of a method for preparing a composite polypeptide bactericidal preparation in one embodiment of the present invention.
Detailed Description
The present invention is further described in detail below with reference to the attached drawings so that those skilled in the art can implement the invention by referring to the description text.
It will be understood that terms such as "having," "including," and "comprising," as used herein, do not preclude the presence or addition of one or more other elements or groups thereof.
The invention provides a composite polypeptide sterilization preparation, which comprises natural biological components and traditional Chinese medicine components, wherein the natural biological components comprise the following components in parts by weight: 0.1-10 parts of antibacterial peptide, 0.01-1 part of melittin and 0.2-1 part of biological lysozyme, wherein the traditional Chinese medicine components comprise 0.1-2 parts of honeysuckle and 0.1-2 parts of isatis root. Preferably, honeysuckle and isatis root adopt respective corresponding traditional Chinese medicine extracts.
Pure plant or biological components hardly meet the sterilization requirements without the assistance of chemical components. Generally, the matching of multi-component products needs to supplement each other, mutual interference cannot occur, and the sterilization time needs to be less than 5min to meet the requirements. The invention adopts the composite polypeptide technology, has no harm and side effect on human health, has unique physiological activity and medical health care function which are not possessed by original protein and monomer amino acid as core components of biological antibacterial peptide, melittin and biological lysozyme, and can kill pathogenic bacteria such as escherichia coli, staphylococcus aureus, helicobacter pylori and the like, oral bacteria and pathogenic bacteria. The invention avoids the addition of chemical components, brings good news especially for people with sensitive part of chemical components, and has broader-spectrum sterilization effect.
In the above aspect, preferably, the natural biological component further includes:
0.1-1 part of natamycin and 83-99.39 parts of pH buffer solution.
In some of the technical solutions of the present invention, it is preferable that the method further includes:
the hydrogel component comprises 1-5 parts of sodium hyaluronate, 0.01-0.5 part of fucoidin, 1-5 parts of chitosan, 0.1-0.6 part of glacial acetic acid and 0.04-0.1 part of towel gourd iron. The towel gourd baking powder is prepared by baking towel gourd and sieving with 100 mesh sieve.
In some of the technical schemes of the present invention, preferably, the antibacterial peptide is nisin or spirulina polypeptide or a mixture of nisin and spirulina polypeptide in a mass ratio of 1: 1. The spirulina polypeptide is derived from spirulina polypeptide by adopting modern biotechnology, and the spirulina polypeptide cuts and separates molecules of phycoprotein and phycocyanin into small molecular fragments, thoroughly changes the structure of original molecules and is a brand-new spirulina polypeptide molecule.
The invention provides a preparation method of the composite polypeptide sterilization preparation, as shown in figure 1, comprising the following steps:
according to parts by weight, 0.1-10 parts of antibacterial peptide, 0.01-1 part of melittin and 0.2-1 part of biological lysozyme are sequentially added into 83-99.39 parts of pH buffer solution and mixed evenly, then 0.1-2 parts of honeysuckle and 0.1-2 parts of radix isatidis are added, and the mixture is emulsified and stirred for about 30 minutes to obtain the composite polypeptide sterilization preparation. Preferably, honeysuckle and isatis root adopt respective corresponding traditional Chinese medicine extracts. And then detecting the content of each component in the composite polypeptide sterilization preparation, adjusting the pH value to 7.35-7.45, subpackaging, spraying a code, labeling, packaging, inspecting again and warehousing.
In some embodiments of the invention, preferably, 0.1-1 part of natamycin is added into the composite polypeptide sterilization preparation.
In some embodiments of the present invention, it is preferable that the method further comprises the following steps:
sequentially adding 0.1-0.6 part by weight of glacial acetic acid, 1-5 parts by weight of chitosan and 0.04-0.1 part by weight of towel gourd iron into water, uniformly stirring, standing for 12 hours, and freeze-drying to obtain a chitosan and towel gourd vegetable sponge compound;
and adding the chitosan and loofah sponge compound into the composite polypeptide sterilization preparation and sterilizing.
In some of the embodiments of the present invention, preferably, the pH buffer is phosphate buffered saline.
In some embodiments of the invention, preferably, the antimicrobial peptide is nisin or spirulina polypeptide or a mixture of nisin and spirulina polypeptide in a mass ratio of 1: 1.
The invention also provides the application of the compound polypeptide sterilization preparation in pathogen killing and preparation of anti-inflammatory and antibacterial drugs.
In order to make the technical solution of the present invention better understood by those skilled in the art, the following examples are now provided for illustration:
the invention belongs to the technical field of sterilization preparations, and discloses a composite polypeptide sterilization, a preparation method and application thereof, wherein the composite polypeptide sterilization preparation consists of natural biological components and traditional Chinese medicine components; wherein the natural biological components comprise, by weight, 0.1-10% of antibacterial peptide, 0.01-1% of melittin, 0.2-1% of biological lysozyme, 0.1-1% of natamycin and 83-99.39% of pH buffer solution; the traditional Chinese medicine components comprise, by weight, 0.1-2% of honeysuckle and 0.1-2% of isatis root. The invention adopts the compound polypeptide technology, has no harm and side effect on human health, can kill pathogenic bacteria such as escherichia coli, staphylococcus aureus, helicobacter pylori and the like, oral bacteria and pathogenic bacteria, has the core components of biological antibacterial peptide, melittin and biological lysozyme, and has unique physiological activity and medical health care effect which are not possessed by original protein and monomer amino acid.
The invention is realized in such a way that the composite polypeptide sterilization preparation consists of natural biological components and traditional Chinese medicine components;
wherein the natural biological components comprise, by weight, 0.1-10% of antibacterial peptide, 0.01-1% of melittin, 0.2-1% of biological lysozyme, 0.1-1% of natamycin and 83-99.39% of pH buffer solution;
the traditional Chinese medicine components comprise, by weight, 0.1-2% of honeysuckle and 0.1-2% of isatis root.
The invention also aims to provide a preparation method of the composite polypeptide sterilization preparation, which applies the composite polypeptide sterilization preparation.
The invention also aims to provide application of the composite polypeptide bactericidal preparation in killing pathogenic bacteria, wherein the pathogenic bacteria comprise escherichia coli, staphylococcus aureus, helicobacter pylori, group A streptococcus and anaerobic streptococcus, staphylococcus epidermidis, neisseria, lactobacillus, spirochete, candida, coronavirus and oral bacteria. The invention has different degrees of bacteriostasis to the pathogenic bacteria, effectively improves the effects of sterilization, bacteriostasis, anti-inflammation and anti-allergy, improves the treatment effect and is convenient to use.
The invention also aims to provide application of the compound polypeptide sterilization preparation in preparing medicines for treating wounds, wiping, falling injuries, incised injuries, diminishing inflammation and fungal infections, promoting wound healing and preventing ear eczema, breast eczema, scrotal eczema, hand eczema, perianal eczema and shank eczema.
The invention also aims to provide application of the compound polypeptide sterilization preparation in preparing medicines for treating red and itchy skin, dryness, desquamation, pruritus, dermatitis blisters, gingivitis of oral cavity of human, glossitis, oral ulcer, dental calculus, halitosis, bromhidrosis and bromhidrosis.
The composite polypeptide sterilization preparation provided by the embodiment of the invention consists of natural biological components and traditional Chinese medicine components;
wherein the natural biological components comprise, by weight, 0.1-10% of antibacterial peptide, 0.01-1% of melittin, 0.2-1% of biological lysozyme, 0.1-1% of natamycin and 83-99.39% of pH buffer solution;
the traditional Chinese medicine components comprise, by weight, 0.1-2% of honeysuckle and 0.1-2% of isatis root.
The composite polypeptide antibacterial agent comprises the following raw material components: natural biological components, solutions of traditional Chinese medicine components; according to weight percentage, 0.1-10% of antibacterial peptide, 0.01-1% of melittin, 0.2-1% of biological lysozyme are used as main components, 0.1-1% of natamycin, 0.1-2% of traditional Chinese medicine component honeysuckle, 0.1-2% of radix isatidis and 83-99.39% of pH buffer solution; the polypeptide antibacterial agent has obvious effective killing and inhibiting effects on escherichia coli, staphylococcus aureus, helicobacter pylori and coronavirus on hands and skin mucous membranes, has good antibacterial effects on streptococcus group A, anaerobic streptococcus, staphylococcus epidermidis, Neisseria (Neisseria), Lactobacillus (Lactobacillus), spirochete (Spirochaeta), Candida (Candida) and the like which are frequently existed in oral cavities, eliminates pathogenic microorganisms outside human bodies, cuts off the transmission path of infectious diseases and achieves the purpose of controlling the infectious diseases. The product has good stability, strong antibacterial activity and broad-spectrum bactericidal effect, and can be used as substitute of the existing chemical disinfectants, bactericides, skin repair liquid and skin mucosa disinfectant. The compound polypeptide antibacterial agent can be used for treating skin mucosa diseases and preventing oral diseases such as oral gingivitis, glossitis, oral ulcer, dental calculus, halitosis, etc., and has oral deodorizing, antibacterial, antiinflammatory, and antiallergic effects.
The technical solution of the present invention is further described below in connection with pharmacological analysis.
1. Biological antibacterial peptide: the main effects of the biological peptide have the effects of regulating the metabolism of a human body and regulating physiological functions, promoting digestion, enhancing immunity, resisting bacteria and viruses, reducing blood pressure and blood fat and the like. Experiments have shown that the biological antimicrobial peptides are capable of killing gram-negative and gram-positive bacteria (including those resistant to conventional antibiotics), mycobacteria (including tuberculosis), viruses with a mantle, fungi, and even transformed or cancerous cells. Unlike many traditional antibiotics, antimicrobial peptides can also act as immunomodulators to improve immunity. In addition to killing bacteria directly, antimicrobial peptides also have some immunomodulatory functions that can be involved in the clearance of infection, including the ability to alter host gene expression, act as chemokines-like or induce chemokine production, inhibit endotoxin-induced inflammatory cytokine production, promote wound healing, not only clear infection but also prevent infection. Compared with the traditional antibiotics, the antibacterial peptide seems to have no drug resistance, has a wide bactericidal spectrum and short bactericidal time. Has strong killing effect on part of fungi, protozoa, viruses, cancer cells, etc.
2. Melittin (melittin) has good oxidation resistance, and also has effects of inhibiting and killing various bacteria, and has certain medical value, and can be made into natural chewing gum after special processing to protect teeth and eliminate dental calculus. Melittin has effects of resisting inflammation, inhibiting bacteria, resisting cancer, resisting radiation, inhibiting platelet aggregation, etc., can be used for effectively treating scapulohumeral periarthritis, rheumatic arthritis, rheumatoid arthritis, etc., and has certain application in medicine field. Has wide medical and health care functions for human bodies.
Melittin is obtained by separating and purifying bee venom, has the characteristics of high biological activity, no environmental pollution and the like, has main pharmacological action in bee venom, and is one of substances with strongest anti-inflammation in human at present. It also has hormone-like action, but has no adverse hormone reaction. In addition, melittin can penetrate the protective outer layer of HIV to destroy HIV, but does not damage surrounding normal cells.
3. Biological lysozyme: a natural anti-infective substance with antibacterial effect is provided. The lysozyme has the effects of resisting bacteria, resisting virus, resisting tumor, stopping bleeding, relieving swelling and pain, accelerating tissue recovery and the like. The traditional Chinese medicine composition is clinically used for treating chronic rhinitis, acute and chronic pharyngolaryngitis, oral ulcer, chicken pox, herpes zoster, flat wart and the like. It can also be used in combination with antibacterial agents to treat various bacterial and viral infections. It is effective for oral administration and intramuscular injection.
The components are characterized in that: 1) has the unique advantages of strong antibacterial property, safety, no toxicity, good thermal stability, wide action range and the like. 2) Lysozyme is a protein that is stable to changes in pH and stable to heat under acidic conditions. 3) Lysozyme can dissolve bacterial cells, has a strong effect on G + bacteria (gram-positive bacteria) and has various properties of antibiotics.
4. Natamycin: natamycin is a natural, broad-spectrum, efficient and safe filamentous fungus inhibitor of yeast, mould and the like, and can inhibit fungi and prevent the generation of mycotoxin. Natamycin is harmless to the human body, is difficult to be absorbed by the digestive tract of the human body, is difficult to generate resistance to microorganisms, can be used for treating fungal infection due to the characteristics of low solubility and the like, comprises candida, aspergillus, fusarium and the like, and can also be used as eye drops or oral medicaments, and the absorption of the natamycin by the human body is less in the applications. When administered orally, it is not substantially absorbed from the gastrointestinal tract.
5. Honeysuckle flower: honeysuckle flower, also known as Lonicera japonica (school name). Honeysuckle is named from compendium of materia Medica, and is obtained because honeysuckle flowers turn white at first and then turn yellow. The flos Lonicerae is dried bud or flower with initial blossom of Lonicera Japonica of Lonicera of Caprifoliaceae and plants of the same genus. Honeysuckle is well known for its wide medicinal value since ancient times. The efficacy of the traditional Chinese medicine is mainly to clear away heat and toxic materials and mainly treat epidemic febrile disease fever, heat toxin and bloody dysentery, carbuncle, cellulitis, furuncle and the like. Modern researches prove that the honeysuckle contains pharmacological active ingredients such as chlorogenic acid and luteolin glycoside, has stronger inhibitory power on various pathogenic bacteria such as hemolytic streptococcus, staphylococcus aureus and the like and upper respiratory infection pathogenic viruses and the like, can enhance immunity, resist early pregnancy, protect liver, resist tumor, diminish inflammation, relieve fever, stop bleeding (blood coagulation), inhibit intestinal absorption of cholesterol and the like, has very wide clinical application, and can be used for treating more than 40 diseases such as respiratory infection, bacillary dysentery, acute urinary infection, hypertension and the like by being compatible with other medicines.
The honeysuckle flower is cold in nature and sweet in taste, enters lung, heart and stomach channels, has the effects of clearing heat and removing toxicity, resisting inflammation, tonifying deficiency and treating wind, and is mainly used for treating diseases such as distending pain, epidemic febrile disease, fever, toxic heat, carbuncle and ulcer, tumor and the like. It has therapeutic effects on dizziness, thirst, hyperhidrosis, vexation, enteritis, bacillary dysentery, measles, pneumonia, encephalitis B, epidemic encephalitis, acute mastitis, septicemia, appendicitis, skin infection, carbuncle, furuncle, erysipelas, parotitis, and suppurative tonsillitis.
6. Radix isatidis: is dried root of Isatis indigotica indica fort. belonging to Isatis of Brassicaceae. Has the effects of clearing away heat and toxic materials, cooling blood, and relieving sore throat. Mainly treats exogenous fever, early warm disease, swollen and sore throat, warm poison and macula, mumps, erysipelas, carbuncle and sore toxin. Has inhibitory effect on various gram-positive bacteria, gram-negative bacteria, influenza virus, arbovirus and parotid virus; can enhance the immune function; has obvious antipyretic effect. The indirubin contained in the product has remarkable anti-leukemia effect; the isatis root polysaccharide can reduce the contents of serum cholesterol and triglyceride of experimental animals and reduce the content of MDA, thereby proving that the isatis root polysaccharide has antioxidation.
7. The towel gourd iron is a net formed by interweaving a plurality of layers of filamentous fibers, fucoidin is rich in L-fucose and sulfate groups, is combined with chitosan, is a pure natural biological material, and the formed hydrogel has better biocompatibility and has the characteristics of no adhesion and bacteriostasis.
Example 1
The composite polypeptide sterilization preparation consists of natural biological components and traditional Chinese medicine components, wherein the natural biological components consist of 0.1 percent of antibacterial peptide, 0.01 percent of melittin, 0.2 percent of biological lysozyme, 0.1 percent of natamycin and 93.99 percent of pH buffer solution according to weight percentage; the traditional Chinese medicine components comprise 0.1 percent of honeysuckle and 0.1 percent of isatis root.
The preparation method of the composite polypeptide sterilization preparation comprises the following steps: and sequentially adding the antibacterial peptide, the melittin and the biological lysozyme into the pH buffer solution, uniformly mixing, then adding the honeysuckle and the isatis root, emulsifying and stirring for about 30 minutes to obtain the compound polypeptide bactericidal preparation.
Example 2
The composite polypeptide sterilization preparation consists of natural biological components and traditional Chinese medicine components, wherein the natural biological components consist of 10 percent of antibacterial peptide, 1 percent of melittin, 1 percent of biological lysozyme, 1 percent of natamycin and 83 percent of pH buffer solution according to weight percentage; the traditional Chinese medicine components comprise 2 percent of honeysuckle and 2 percent of isatis root.
The preparation method of the composite polypeptide sterilization preparation comprises the following steps: and sequentially adding the antibacterial peptide, the melittin and the biological lysozyme into the pH buffer solution, uniformly mixing, then adding the honeysuckle and the isatis root, emulsifying and stirring for about 30 minutes to obtain the compound polypeptide bactericidal preparation.
Example 3
The compound polypeptide sterilization preparation consists of natural biological components and traditional Chinese medicine components, wherein the traditional Chinese medicine components consist of 1 percent of honeysuckle and 1 percent of isatis root according to weight percentage. The natural biological components comprise 5% of antibacterial peptide, 0.05% of melittin, 0.6% of biological lysozyme, 0.55% of natamycin and 85.4% of pH buffer solution;
the preparation method of the composite polypeptide sterilization preparation comprises the following steps: and sequentially adding the antibacterial peptide, the melittin and the biological lysozyme into the pH buffer solution, uniformly mixing, then adding the honeysuckle and the isatis root, emulsifying and stirring for about 30 minutes to obtain the compound polypeptide bactericidal preparation.
Example 4
The composite polypeptide sterilization preparation comprises natural biological components, traditional Chinese medicine components and hydrogel components, wherein the natural biological components comprise the following components in parts by weight: 0.1 part of antibacterial peptide, 0.01 part of melittin, 0.2 part of biological lysozyme, 0.1 part of natamycin and 83 parts of pH buffer solution, wherein the traditional Chinese medicine components comprise 0.1 part of honeysuckle and 0.1 part of isatis root. The antibacterial peptide is nisin or spirulina polypeptide or a mixture of nisin and spirulina polypeptide in a mass ratio of 1: 1. The pH buffer is phosphate buffered saline (pH 7.4). The hydrogel component comprises 1 part of sodium hyaluronate, 0.01 part of fucoidin, 1 part of chitosan, 0.1 part of glacial acetic acid and 0.04 part of towel gourd iron.
The preparation method of the composite polypeptide sterilization preparation comprises the following steps:
and sequentially adding the antibacterial peptide, the melittin, the biological lysozyme and the natamycin into the pH buffer solution, uniformly mixing, then adding the honeysuckle and the isatis root, emulsifying and stirring for about 30 minutes to obtain the composite polypeptide bactericidal preparation. Flos Lonicerae and radix Isatidis adopt their corresponding Chinese medicinal extracts.
Sequentially adding glacial acetic acid, chitosan and loofah into water, uniformly stirring, standing for 12 hours, and freeze-drying to obtain a chitosan and loofah sponge compound; and adding the chitosan and loofah sponge compound into the composite polypeptide sterilization preparation and sterilizing.
Example 5
The composite polypeptide sterilization preparation comprises natural biological components, traditional Chinese medicine components and hydrogel components, wherein the natural biological components comprise the following components in parts by weight: 5 parts of antibacterial peptide, 0.5 part of melittin, 0.6 part of biological lysozyme, 0.5 part of natamycin and 90 parts of pH buffer solution, wherein the traditional Chinese medicine components comprise 1 part of honeysuckle and 12 parts of isatis root. The antibacterial peptide is spirulina polypeptide. The pH buffer is phosphate buffered saline (pH 7.4). The hydrogel component comprises 3 parts of sodium hyaluronate, 0.3 part of fucoidin, 3 parts of chitosan, 0.35 part of glacial acetic acid and 0.07 part of towel gourd.
The preparation method of the composite polypeptide sterilization preparation comprises the following steps:
and sequentially adding the antibacterial peptide, the melittin, the biological lysozyme and the natamycin into the pH buffer solution, uniformly mixing, then adding the honeysuckle and the isatis root, emulsifying and stirring for about 30 minutes to obtain the composite polypeptide bactericidal preparation. Flos Lonicerae and radix Isatidis adopt their corresponding Chinese medicinal extracts.
Sequentially adding glacial acetic acid, chitosan and loofah into water, uniformly stirring, standing for 12 hours, and freeze-drying to obtain a chitosan and loofah sponge compound; and adding the chitosan and loofah sponge compound into the composite polypeptide sterilization preparation and sterilizing.
Example 6
The composite polypeptide sterilization preparation comprises natural biological components, traditional Chinese medicine components and hydrogel components, wherein the natural biological components comprise the following components in parts by weight: 10 parts of antibacterial peptide, 1 part of melittin, 1 part of biological lysozyme, 1 part of natamycin and 83-99.39 parts of pH buffer solution, wherein the traditional Chinese medicine components comprise 2 parts of honeysuckle and 2 parts of isatis root. The antibacterial peptide is a mixture of nisin and spirulina polypeptides in a mass ratio of 1: 1. The pH buffer is phosphate buffered saline (pH 7.4).
The hydrogel component comprises 5 parts of sodium hyaluronate, 0.5 part of fucoidin, 5 parts of chitosan, 0.6 part of glacial acetic acid and 0.1 part of towel gourd iron.
The preparation method of the composite polypeptide sterilization preparation comprises the following steps:
and sequentially adding the antibacterial peptide, the melittin, the biological lysozyme and the natamycin into the pH buffer solution, uniformly mixing, then adding the honeysuckle and the isatis root, emulsifying and stirring for about 30 minutes to obtain the composite polypeptide bactericidal preparation. Flos Lonicerae and radix Isatidis adopt their corresponding Chinese medicinal extracts.
Sequentially adding glacial acetic acid, chitosan and loofah into water, uniformly stirring, standing for 12 hours, and freeze-drying to obtain a chitosan and loofah sponge compound; and adding the chitosan and loofah sponge compound into the composite polypeptide sterilization preparation and sterilizing.
The invention has different degrees of bacteriostasis to pathogenic bacteria such as escherichia coli, staphylococcus aureus, helicobacter pylori, flora type A streptococcus, anaerobic streptococcus, staphylococcus epidermidis, neisseria, lactobacillus, spirochete, candida, coronavirus, oral bacteria and the like, effectively improves the effects of sterilization, bacteriostasis, anti-inflammation and anti-allergy, improves the sterilization effect and is convenient to use.
The number of modules and the processing scale described herein are intended to simplify the description of the invention. The application, modification and variation of the inventive penstock stiffening ring will be apparent to those skilled in the art.
While embodiments of the invention have been described above, it is not limited to the applications set forth in the description and the embodiments, which are fully applicable in various fields of endeavor to which the invention pertains, and further modifications may readily be made by those skilled in the art, it being understood that the invention is not limited to the details shown and described herein without departing from the general concept defined by the appended claims and their equivalents.

Claims (10)

1. The compound polypeptide sterilization preparation is characterized by comprising natural biological components and traditional Chinese medicine components, wherein the natural biological components comprise the following components in parts by weight: 0.1-10 parts of antibacterial peptide, 0.01-1 part of melittin and 0.2-1 part of biological lysozyme, wherein the traditional Chinese medicine components comprise 0.1-2 parts of honeysuckle and 0.1-2 parts of isatis root.
2. The complex polypeptide bactericidal formulation of claim 1 wherein the natural biological components further comprise:
0.1-1 part of natamycin and 83-99.39 parts of pH buffer solution.
3. The complex polypeptide bactericidal formulation of claim 1, further comprising:
the hydrogel component comprises 1-5 parts of sodium hyaluronate, 0.01-0.5 part of fucoidin, 1-5 parts of chitosan, 0.1-0.6 part of glacial acetic acid and 0.04-0.1 part of towel gourd iron.
4. The composite polypeptide bactericidal formulation of claim 1, wherein the antimicrobial peptide is nisin or spirulina polypeptide or a mixture of nisin and spirulina polypeptide in a mass ratio of 1: 1.
5. The method for preparing the composite polypeptide sterilization preparation according to claim 1, which comprises the following steps:
according to parts by weight, 0.1-10 parts of antibacterial peptide, 0.01-1 part of melittin and 0.2-1 part of biological lysozyme are sequentially added into 83-99.39 parts of pH buffer solution and mixed evenly, then 0.1-2 parts of honeysuckle and 0.1-2 parts of radix isatidis are added, and the mixture is emulsified and stirred for about 30 minutes to obtain the composite polypeptide sterilization preparation.
6. The method for preparing the composite polypeptide bactericidal preparation according to claim 5, wherein 0.1 to 1 part of natamycin is added to the composite polypeptide bactericidal preparation.
7. The method for preparing the composite polypeptide sterilization preparation according to claim 5, further comprising the steps of:
sequentially adding 0.1-0.6 part by weight of glacial acetic acid, 1-5 parts by weight of chitosan and 0.04-0.1 part by weight of towel gourd iron into water, uniformly stirring, standing for 12 hours, and freeze-drying to obtain a chitosan and towel gourd vegetable sponge compound;
and adding the chitosan and loofah sponge compound into the composite polypeptide sterilization preparation and sterilizing.
8. The method for preparing the composite polypeptide bactericidal formulation of claim 5, wherein the pH buffer is phosphate buffered saline.
9. The method for preparing the composite polypeptide bactericidal preparation according to claim 5, wherein the antibacterial peptide is nisin or spirulina polypeptide or a mixture of nisin and spirulina polypeptide in a mass ratio of 1: 1.
10. The use of the composite polypeptide bactericidal agent of claim 1 in killing pathogenic bacteria and preparing anti-inflammatory and antibacterial medicaments.
CN202111462334.7A 2021-12-02 2021-12-02 Composite polypeptide sterilization preparation and preparation method and application thereof Pending CN114028546A (en)

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CN117143847A (en) * 2023-08-30 2023-12-01 江苏好多收农业科技有限公司 Preparation process and application of polypeptide hydrogel supported biological enzyme

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CN105251045A (en) * 2015-10-20 2016-01-20 青岛明月生物医用材料有限公司 Fucoidin-containing biomedical hydrogel and preparation method thereof
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