Multi-amino positive ion compound and application thereof in biological bacteriostasis / virus resistance

Abstract

The invention discloses a polyamino positive ion compound and application thereof in biological bacteriostasis / virus resistance, and particularly relates to the field of biological medicine. The invention also discloses application of the polyamino positive ion compound in preparation of biological antibacterial / antiviral products related to biological mucous membranes or skin lesion parts. Nucleic acid biological macromolecules are introduced into the compound to form the compound with a reticular macromolecular structure, so that the compound has a good wrapping and disinfecting effect on pathogens and has a good adhesion effect on mucous membrane tissues or skin lesion parts, and the antibacterial and / or virus-inhibiting effect of polyamino positive ions on the mucous membrane tissues is enhanced; no irritation is caused to mucous membrane tissues; the composition is environment-friendly, animal-friendly or human-body-friendly; the introduced nucleic acid biomacromolecules can excite immune response in mucosa tissues or skin lesion parts of animals and human bodies and synergistically clear pathogenic microorganisms, and the compound can be used in the field of disinfection and bacteriostasis articles for human and veterinary use to inhibit pathogenic microorganism infection and also can be used as a mucosa adjuvant.

Description

Technical Field

[0001] This invention relates to the field of biomedicine, specifically to a polyamino cation complex and its application in biological antibacterial / antiviral activity. Background Technology

[0002] Biological antimicrobial preservatives refer to a class of highly effective preservatives obtained from organisms through biological culture, extraction, and separation techniques, which have the effect of inhibiting and killing microorganisms. Food is rich in nutrients and is highly susceptible to microbial contamination and spoilage. To ensure food safety, many methods are used for food preservation, such as salting, canning, and refrigeration. However, under certain conditions, the combined use of preservatives as an auxiliary means of preservation can significantly prevent food spoilage. Therefore, preservatives remain an important food additive and are widely used in the food industry.

[0003] ε-Polylysine is a microbial food preservative with excellent preservative properties and great commercial potential among natural preservatives. It is a novel polymer discovered by Drs. Heiichi Sakai and Shoji Shima in Japan during extensive screening of valuable actinomycetes. It is polymerized from 25-30 lysine residues, and further research has shown that it has strong antibacterial capabilities and can be used as a preservative for food preservation.

[0004] ε-Polylysine has a broad antibacterial spectrum and exhibits certain antibacterial effects against Gram-positive bacteria, Gram-negative bacteria, yeasts, and molds in both acidic and slightly acidic environments. ε-Polylysine has a very good antibacterial effect against Gram-negative Escherichia coli and Salmonella, which are not easily inhibited by other natural preservatives. Moreover, it also has an inhibitory effect on heat-resistant Bacillus and some viruses.

[0005] In 2003, Hiraki J et al. used ADME (an ADME developed in recent years by Thermo Fisher Scientific, integrating absorption, distribution, metabolism, excretion, and toxicity) to confirm the safety of ε-polylysine as a food preservative. They conducted a series of pharmacokinetic and metabolic pathway studies on ε-polylysine in mice to understand why there were no toxicological effects in sub- and chronic feeding bioassays with up to 50,000 mg / kg of ε-polylysine in the mice's diet. Acute oral toxicity experiments in mice revealed that ε-polylysine is actually non-toxic, with a mortality rate of 0% at oral doses up to 5 g / kg.

[0006] ε-Polylysine requires only trace amounts to be effective in food without affecting its taste, making it a natural food preservative. It is natural and safe, meeting consumers' health needs. In Japan, the production of ε-Polylysine as a food preservative has developed rapidly, with a market size reaching billions of yen. When applied to pastries and bread, ε-Polylysine effectively inhibits the proliferation of heat-resistant Bacillus subtilis, extending shelf life; in low-sugar, low-calorie foods, such as milk protein ice cream and cream products, it improves their shelf life; adding trace amounts of ε-Polylysine to chilled canned foods prevents off-flavors after sterilization; and adding ε-Polylysine to refrigerated foods helps maintain quality.

[0007] When ε-polylysine is used as an antibacterial agent in food, it is usually combined with other substances to achieve synergistic effects and cost-effectiveness. Commonly used compounding substances can be divided into five categories: 1. Alcohol, used at 30-70%, mainly applied to various egg products. 2. Organic acids, commonly used organic acids include acetic acid, malic acid, maleic acid, citric acid, succinic acid, etc., used at 0.5-50%, mainly applied to rice, beverages, salads, sauces, etc. 3. Glycerides, mostly lower fatty acid esters, used at 0.01-5%, mainly used in foods rich in animal protein and milk protein. 4. Glycine, used at 0.01-10%; mainly used for milk preservation. 5. Other natural antibacterial agents, such as protamine sulfate, tea polyphenols, etc.

[0008] Chitosan, chemically known as polyglucosamine (1-4)-2-amino-BD glucose, is obtained from chitin through deacetylation. Generally, chitosan is defined as having more than 55% of its N-acetyl groups removed. Chitosan is soluble in dilute acids, a significant improvement over chitin. However, both chitin and chitosan are large molecules with molecular weights ranging from hundreds of thousands to millions, and are insoluble in water. Chitosan is obtained by deacetylation of chitin, and further degradation yields chitosan oligosaccharides. Under specific conditions, chitosan can undergo chemical reactions such as hydrolysis, alkylation, acylation, carboxymethylation, sulfonation, nitration, halogenation, oxidation, reduction, condensation, and complexation, generating various chitosan derivatives with different properties, thus expanding the application range of chitosan.

[0009] Chitosan macromolecules contain reactive hydroxyl and amino groups, which possess strong chemical reactivity. Under alkaline conditions, the hydroxyl group at C-6 can undergo the following reactions: Hydroxyethylation—Chitosan reacts with ethylene oxide to yield hydroxyethylated derivatives. Carboxymethylation—Chitosan reacts with chloroacetic acid to yield carboxymethylated derivatives. Sulfonation—Chitin and chitosan, like cellulose, can react with carbon disulfide after alkali treatment to form sulfonates. Cyanoethylation—Acrylonitrile and chitosan can undergo an addition reaction to form cyanoethylated derivatives.

[0010] The above reaction introduces large side groups into chitin and chitosan, disrupting their crystalline structure and thus increasing their solubility. They are soluble in water, and the carboxymethylated derivatives exhibit polyelectrolyte properties in solution.

[0011] Chitosan and its derivatives possess good antibacterial activity, inhibiting the growth and reproduction of some fungi, bacteria, and viruses. As of 2013, three possible mechanisms were identified: first, the polycations of chitosan readily interact with negatively charged groups on the surface of fungal cells, thereby altering the fluidity and permeability of the pathogenic cell membrane; second, they interfere with DNA replication and transcription; and third, they block pathogen metabolism. Since 2010, many researchers have proposed that chitosan achieves its antibacterial effect by inducing pathogenesis-related proteins, accumulating secondary metabolites, and signal transduction. Chitosan is readily soluble in weakly acidic solvents. Notably, the dissolved solution contains amino groups (NH2+), which inhibit bacteria by binding negative electrons. The antibacterial activity of chitosan has led to its wide application in medicine, textiles, and food.

[0012] Papineau et al. proposed that the interaction between the positive charge of chitosan molecules and the negative charge on bacterial cell membranes causes leakage of intracellular proteases and other components, thereby achieving antibacterial and bactericidal effects. Their research found that chitosan lactate at a concentration of 0.12 mg / mL effectively inhibited the growth of *Escherichia coli*, and chitosan glutamate also showed good inhibitory effects on yeasts such as *Saccharomyces cerevisiae*. Furthermore, 1 mg / mL of chitosan lactate completely inactivated yeast within 17 minutes. Sudharshan et al. pointed out that chitosan can penetrate into the bacterial nucleus and bind to DNA, inhibiting mRNA synthesis and thus hindering the synthesis of mRNA and proteins, achieving antibacterial effects. They studied the effects of water-soluble chitosans, such as chitosan lactate, chitosan glutamate, and chitosan hydrogenated glutamate, on the culture of different bacteria. The results showed that chitosan lactate and chitosan glutamate had high antibacterial activity against both Gram-positive and Gram-negative bacteria.

[0013] Studies by Ghaoth et al. showed that strawberry spoilage caused by B. cinerea or R. stolonifer was significantly inhibited after coating with chitosan solution, extending the shelf life of strawberries. Other studies reported that chitosan with different molecular weights had varying preservative effects, with those around 200,000 and 10,000 molecular weights being the most effective. Furthermore, in 2013, most preservatives used in condiments were benzoic acid and its sodium salt. Compared to benzoic acid, under the same storage conditions, chitosan has a stronger antibacterial effect, requires less dosage, has a better taste, and has no toxic side effects, making it an ideal preservative for condiments. Yang Jisheng et al. studied the preservative effect of chitosan on soy sauce. The results showed that adding 0.1% chitosan to soy sauce significantly inhibited the yeast population that causes soy sauce spoilage. Under open conditions in summer, it could be stored for 30 days without spoiling, and its taste, color, aroma, and composition were not affected.

[0014] Chitosan promotes blood clotting and can be used as a hemostatic agent. It can also be used as a wound filler, possessing properties such as sterilization, promoting wound healing, absorbing wound exudate, and resisting dehydration and shrinkage.

[0015] Chitosan possesses a series of biological effects that activate and mediate bodily systems, enhancing the systemic function of phagocytes. Macrophages have receptors for bacterial polysaccharides on their surface, and chitosan, as an analogue of bacterial polysaccharides, can stimulate macrophage activation, leading to the following responses: promoting phagocytosis and enhancing its synergistic effect in other immune responses. This, in turn, enables the body to regulate T cells, NK cells, and B cells, mediating both cellular and humoral immune responses. Therefore, chitosan has an immunomodulatory effect on the body.

[0016] Both ε-polylysine and chitosan can be used as biological antibacterial agents, which have a good inhibitory effect on microorganisms such as bacteria, yeast, and fungi. They have a significant inhibitory effect on bacteria commonly found on the human skin, such as Staphylococcus epidermidis, Escherichia coli, and Candida tropicalis, as well as Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus pyogenes infections that are common in burn patients.

[0017] Nucleic acids are a collective term for deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), and are biological macromolecules composed of many nucleotide monomers. Nucleic acids are composed of nucleotides, and nucleotide monomers are composed of pentose sugars, phosphate groups, and nitrogenous bases. If the pentose sugar is ribose, the polymer formed is RNA; if the pentose sugar is deoxyribose, the polymer formed is DNA. A common artificially prepared double-stranded RNA is polyinosinic-polycytidylic acid (poly(I:C)), which is a double-stranded product of the pairing of artificially synthesized polyinosine nucleotide (PolyI) and polycytosine nucleotide (PolyC). A common artificially prepared double-stranded DNA is CPG ODN (CpG oligonucleotide), which is an artificially synthesized oligodeoxynucleotide (ODN) containing unmethylated cytosine-guanine dinucleotide (CpG). Based on structure and biological characteristics, CpG ODN can be classified into type A, type B, and type C.

[0018] ε-Polylysine is widely used as a bioantibacterial agent in food, but its application in mucous membranes or skin lesions in animals and humans is rarely reported. Chitosan and nucleic acid biomolecules have immunomodulatory effects on the body. There are currently no reports on the use of ε-Polylysine, chitosan, and nucleic acid biomolecules in a compound for bioantibacterial / antiviral purposes. Summary of the Invention

[0019] Therefore, the present invention provides a polyamino positive ion complex and its application in biological antibacterial / antiviral activity to solve the problem that it is not currently used on mucous membranes or skin lesions in animals or humans.

[0020] The purpose of this invention is to provide a polyamino positive ion complex with antibacterial and / or antiviral effects that can be applied to mucosal tissues and skin lesions of animals or humans. Therefore, this invention provides a polyamino positive ion complex with antibacterial and / or antiviral effects, the basis of which is a complex composed of polyamino positive ions and nucleic acid biomacromolecules. When applied to mucosal tissues or skin lesions of animals or humans, it inhibits the infection of pathogenic microorganisms and can also be used as a mucosal adjuvant.

[0021] This invention develops a polyamino positive ion complex with antibacterial and / or antiviral effects that can be applied to mucosal tissues or skin lesions in animals and humans.

[0022] To achieve the above objectives, the present invention provides the following technical solution:

[0023] The application of a polyamino cation complex provided by the first aspect of the present invention in the preparation of biological antibacterial products for biological mucosa or skin lesions.

[0024] The second aspect of the present invention provides the application of a polyamino cation complex in the preparation of biological antiviral products for biological mucosa or skin lesions.

[0025] According to a third aspect of the present invention, a polyamino positive ion complex is provided, wherein the complex is a complex formed by the mutual compounding of polyamino positive ions and nucleic acid biomolecules; wherein the ratio of polyamino positive ions to nucleic acid biomolecules is greater than 1:1.

[0026] Furthermore, the amount of nucleic acid biomacromolecules added is 0.02% to 2% (m / v); based on the complete neutralization of the nucleic acid biomacromolecule anions by the amount of polyamino ions, the additional amount of polyamino ions added is 0.01% to 30% (m / v).

[0027] Normally, polyamino cations (ε-polylysine and / or chitosan) have antibacterial effects when used alone. Their antibacterial effect mainly relies on the binding of the cations in the polyamino cations with bacteria and viruses, thereby inactivating them. However, the antibacterial and antiviral effects of polyamino cations are usually reduced when combined with anionic substances. But the inventors later discovered by adjusting the ratio of the anionic charge to the cation charge of the amino group in the polyamino cation (the ratio of polyamino cation to nucleic acid biomolecules is greater than 1:1) that, when this ratio is met, not only is the antibacterial and antiviral effect of polyamino cations not reduced, but the complex of polyamino cations and nucleic acid biomolecules can enhance their adhesion to damaged sites and stimulate the immune response at the damaged sites, thus enhancing their antibacterial and antiviral effects.

[0028] Furthermore, the nucleic acid biomolecules are one or more of DNA or its derivatives, RNA or its derivatives.

[0029] Furthermore, the DNA or its derivatives, as an example, are preferably CPG ODN.

[0030] Furthermore, the RNA or its derivatives, for example, preferably PolyIC.

[0031] Furthermore, the polyamino cation refers to chitosan and / or ε-polylysine.

[0032] Furthermore, the chitosan is polyglucosamine (1-4)-2-amino-BD glucose or a derivative thereof.

[0033] Furthermore, the ε-polylysine refers to a cationic ε-amino isomeric monomer polymer containing 25-30 lysine residues.

[0034] Furthermore, the complex also includes a pH adjuster during the compounding process. Preferably, the complex formed by the simple compounding of ε-polylysine and nucleic acid biomacromolecules has a pH greater than 8 and less than 9.

[0035] The present invention has the following advantages:

[0036] The polyamino cation complex of this invention introduces nucleic acid-like biomolecules, forming a network macromolecular structure that effectively encapsulates and disinfects pathogens. It also exhibits good adhesion to mucous membranes or skin lesions, enhancing the antibacterial and / or antiviral effects of polyamino cations on mucous membranes. The polyamino cation complex formed by introducing nucleic acid-like biomolecules is non-irritating to mucous membranes. The polyamino cation complex and its digestion and decomposition products are environmentally friendly, animal-friendly, and have no toxic side effects. The introduced nucleic acid-like biomolecules can stimulate an immune response in animal and human mucous membranes or skin lesions, synergistically clearing pathogenic microorganisms. This type of polyamino cation complex can be used in the field of human and veterinary disinfection and antibacterial products to inhibit pathogenic microorganism infection, and can also be used as a mucosal adjuvant. Detailed Implementation

[0037] The following specific embodiments illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0038] Complex: refers to a combination of two or more different substances. When a complex exhibits chemical, mechanical, and physical properties that differ significantly from the individual components, these components retain their original properties. This invention refers to complexes formed by the interaction of polyamino cations and nucleic acid-like biomolecules.

[0039] The polyamino cations and nucleic acid biomolecules involved in this invention can be fully mixed in solid form first, and then a solvent is added for a complexation reaction. Alternatively, they can be complexed in solid-liquid or liquid-liquid forms. The amount, order of addition, and reaction conditions of the reactants can be adjusted appropriately. Polyamino cations may exhibit reduced activity upon contact with acidic polysaccharides, hydrochlorides, borates, phosphates, copper ions, etc. Therefore, when adding dispersants or pharmaceutical excipients such as carbomer to the polyamino cation complex, the type and amount of dispersant or pharmaceutical excipient should be carefully considered. The resulting polyamino cation complex solution can be used on the mucous membranes of the lumens of digestive, respiratory, urinary, and reproductive organs in animals or humans, as well as on skin lesions, to inhibit pathogenic microbial infection. It can also be used as a mucosal adjuvant. Specific preparation methods and test results for some complexes are detailed in the various embodiments.

[0040] Example 1

[0041] A 1% concentration ε-polylysine solution and a 1 mol / L calcium chloride solution were filtered and sterilized separately, and set aside. A freshly prepared 1 mg / ml concentration polyinosinic-polycytidylic acid (PIC) solution was filtered and sterilized, and 50 ml was placed in a sterile beaker. 50 ml of the above ε-polylysine solution was taken and thoroughly mixed with the PIC solution, and then a 10 mmol / L calcium chloride solution and an appropriate amount of pH adjuster were added and thoroughly mixed to prepare ε-polylysine complex A with antibacterial activity.

[0042] Example 2

[0043] Filter and sterilize a 1% concentration of ε-polylysine, and set aside. Filter and sterilize a 1 mg / ml concentration of CPG ODN2395 solution, and place 50 ml in a sterile beaker. Take 50 ml of the above ε-polylysine solution and an appropriate amount of pH adjuster, and mix thoroughly to prepare ε-polylysine complex B with antibacterial activity.

[0044] Example 3

[0045] Filter and sterilize 1% concentration of ε-polylysine, set aside. Filter and sterilize 1 mg / ml concentration of CPG ODN2395, set aside. Then filter and sterilize freshly prepared 1 mg / ml concentration of polyinosinic-polycytidylic acid (poly I:C), take 25 ml and place it in a sterile beaker, then add 25 ml of the above 1 mg / ml concentration of CPG ODN2395 solution. Take 50 ml of the above ε-polylysine solution and an appropriate amount of pH adjuster, mix thoroughly to prepare ε-polylysine complex C with antibacterial activity.

[0046] Example 4

[0047] Prepare a 2% chitosan solution for later use. After filtration and sterilization, take 50 ml of the freshly prepared 1 mg / ml polyinosinic-polycytidylic acid solution and place it in a sterile beaker. Take 50 ml of the above chitosan solution and an appropriate amount of pH adjuster, and mix thoroughly to prepare chitosan complex A with antibacterial properties.

[0048] Example 5

[0049] Prepare a 2% chitosan solution for later use. After sterilizing a 1 mg / ml CPG ODN2395 solution by filtration, take 50 ml and place it in a sterile beaker. Take 50 ml of the above chitosan solution and an appropriate amount of pH adjuster, and mix thoroughly to prepare chitosan complex B with antibacterial properties.

[0050] Example 6

[0051] Prepare a 2% chitosan solution for later use. Filter and sterilize a 1 mg / ml CPG ODN2395 solution and set aside. Filter and sterilize a freshly prepared 1 mg / ml polyinosinic-polycytidylic acid (poly I:C) solution, take 25 ml and place it in a sterile beaker, then add 25 ml of the above 1 mg / ml CPG ODN2395 solution. Take 50 ml of the above chitosan solution and an appropriate amount of pH adjuster, and mix thoroughly to prepare chitosan complex C with antibacterial properties.

[0052] Example 7

[0053] Filter and sterilize a 1% concentration of ε-polylysine solution, and set aside. Prepare a 2% concentration of chitosan solution, and set aside. Filter and sterilize a freshly prepared 1 mg / ml concentration of polyinosinic-polycytidylic acid solution, and place 50 ml into a sterile beaker. Take 25 ml each of the above chitosan solution and ε-polylysine solution, and an appropriate amount of pH adjuster, and mix thoroughly to prepare chitosan-ε-polylysine complex A, which has antibacterial and immunomodulatory effects.

[0054] Example 8

[0055] Filter and sterilize a 1% concentration of ε-polylysine solution, and set aside. Prepare a 2% concentration of chitosan solution, and set aside. Filter and sterilize a 1 mg / ml concentration of CPG ODN2395 solution, and place 50 ml into a sterile beaker. Take 25 ml each of the above chitosan solution and ε-polylysine solution, and add an appropriate amount of pH adjuster, and mix thoroughly to prepare chitosan-ε-polylysine complex B, which has antibacterial and immunomodulatory effects.

[0056] Example 9

[0057] Filter and sterilize a 1% concentration of ε-polylysine solution, and set aside. Prepare a 2% concentration of chitosan solution, and set aside. Filter and sterilize a freshly prepared 1 mg / ml concentration of polyinosinic-polycytidylic acid (PCI) solution, take 25 ml and place it in a sterile beaker, then add 25 ml of the above 1 mg / ml concentration of CPG ODN2395 solution. Take 25 ml each of the above chitosan solution and acidic ε-polylysine solution, and an appropriate amount of pH adjuster, and mix thoroughly to prepare a chitosan-ε-polylysine complex C with antibacterial properties.

[0058] Experimental Example 1

[0059] Tests on the antibacterial infection activity of the complexes in Examples 1-9 in animals:

[0060] TAP method to disrupt mouse skin barrier: 6-8 week old, female, clean-grade BALB / c mice were randomly divided into: blank control group, positive control group, disinfectant control group, and experimental sample group. ε-polylysine complex, chitosan complex, and chitosan-ε-polylysine complex were respectively represented by disinfectant control group 1, disinfectant control group 2, and disinfectant control group 3 in polyamino positive ion solutions of the same concentration, with 10 mice in each group. The mice in each group underwent hair removal cream treatment on their necks (1cm × 2cm) the day before the experiment. On the day of the experiment, mice were anesthetized by intraperitoneal injection of 10% urethane (10ml / kg). The same operator applied medical tape tightly to the skin at the hair removal site with approximately the same force, pressing it repeatedly with a finger 10 times before tearing it off. The tape was replaced after each application and removal process, repeated multiple times to remove the stratum corneum. Animal infection: A concentration of 10% urethane was injected into the TAP lesions. 6 CFU / ml Staphylococcus aureus bacterial suspension was administered to the positive control group, disinfectant control group, and experimental sample group, with 10 μl per animal. The blank control group was replaced with the same volume of physiological saline. Skin lesion disinfection: 0.5 h after infection, the skin lesions in both the disinfectant control group and the experimental sample group were disinfected. A second disinfection was performed 4 h later. Subsequently, both the disinfectant control group and the experimental sample group underwent disinfection for 2 consecutive days, using 300 μl per lesion site twice daily. Results observation: Animals were observed for 4 days from the start of the experiment. Changes in mouse vital signs, including food and water intake, mental status, weight changes before and at the end of the experiment, and changes at the site of keratin removal were observed. See Table 1 for details.

[0061] Table 1

[0062]

[0063]

[0064] Experimental results show that the compound in Examples 1-9 has better disinfection and antibacterial effects than the disinfectant control group, and has good anti-infection ability and good tolerance in experimental mice.

[0065] Experimental Example 2

[0066] Tests on the mucosal irritation of polyamino cation complexes in Examples 1-9:

[0067] Five white rabbits weighing approximately 1.5 kg each were used. A sample was dripped into their right nostril, and physiological saline was dripped into their left nostril as a control. This was done twice a day for 7 days. The rabbits were observed for redness, congestion, edema, and increased secretions in both nostrils. The results are shown in Table 2.

[0068] Table 2

[0069]

[0070] Experimental results show that the complexes of Examples 1-9 of this invention have low irritation to rabbit nasal mucosa and can be used on the mucosal tissues of the lumens of digestive, respiratory, urinary, and reproductive organs in animals or humans, as well as on skin lesions in animals or humans, to inhibit pathogenic microbial infection.

[0071] Experimental Example 3

[0072] Detection of the antiviral infection ability of polyamino cation complexes in animals in Examples 1-9:

[0073] Mouse immunization: 30 μg of influenza lysate virus hemagglutinin (B / Phuket / 3073 / 2013 (B / Yamagata lineage)-like virus) was added to each milliliter of the example sample to prepare sample (S). Female, clean-grade BALB / c mice aged 4–6 weeks were randomly divided into: a blank control group (physiological saline), a positive control group, a hemagglutinin-only group, and an experimental sample group, with 10 mice in each group. Mice were weighed before the experiment and anesthetized with 1.25% aphthylamine intraperitoneally according to the manufacturer's instructions. After the sample was drawn up using a pipette, 50 μL was instilled into each mouse's nostrils. After instillation, the mice were kept in the instillation position for a period of time to prevent the drug from flowing out and affecting the reliability of the experimental data. The instillation was repeated once after 7 days. Mouse challenge: Fourteen days after the first nasal instillation, mice were weighed and anesthetized with 1.25% aphthylazine via intraperitoneal injection according to the instructions. The positive control group, the hemagglutinin-only group, and the experimental sample group each received approximately 3-5 mice of the influenza virus's mouse median lethal dose (MLD50) by 50 μl of the same subtype virus via nasal instillation. The blank control group was replaced with the same volume of physiological saline. Infection method: 50 μl of the infected influenza subtype virus was placed near the nasal cavity of anesthetized mice, allowing them to inhale it spontaneously. Mice were then observed for 14 consecutive days, with daily weight measurements (a 20% weight loss was considered death), and survival rates were recorded for each group. Specific survival rate results are shown in Table 3.

[0074] Table 3

[0075] Experimental group Experimental results Blank control group Mice survival rate 100% Positive control group Mice survival rate 20% hemagglutinin group Mice survival rate 30% Example 1S Sample Experimental Group Mice survival rate 60% Example 2S Sample Experiment Group Mice survival rate 70% Example 3S Sample Experimental Group Mice survival rate 70% Example 4S Sample Experimental Group Mice survival rate 70% Example 5S Sample Experimental Group Mice survival rate 60% Example 6S Sample Experimental Group Mice survival rate 70% Example 7S Sample Experimental Group Mice survival rate 70% Example 8S Sample Experimental Group Mice survival rate 70% Example 9S Sample Experiment Group Mice survival rate 90%

[0076] Experimental results show that samples S in Examples 1-9 all have good antiviral infection capabilities.

[0077] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Natamycin, glycine, citric acid, nisin, calcium propionate, metal ions, etc., can be added to the complex of the present invention for further enhancement of its antibacterial effect. Suitable excipients can also be added to the complex to formulate sprays, gels, or ointments. For those skilled in the art, the present invention can have various modifications and variations. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

[0078] Although the present invention has been described in detail above with general descriptions and specific embodiments, modifications or improvements can be made to it, which will be obvious to those skilled in the art. Therefore, all such modifications or improvements made without departing from the spirit of the present invention fall within the scope of protection claimed by the present invention.

Claims

1. The application of a polyamino positive ion complex in the preparation of bio-antibacterial products for biological mucosa or skin lesions.

2. The application of a polyamino positive ion complex in the preparation of biological antiviral products for biological mucosa or skin lesions.

3. A polyamino cation complex, characterized in that, The complex is a complex composed of polyamino cations and nucleic acid biomolecules; wherein the ratio of polyamino cations to nucleic acid biomolecules is greater than 1:

1.

4. The polyamino cation complex according to claim 3, characterized in that, The amount of nucleic acid biomacromolecules added is 0.02% to 2% (m / v); on the basis that the amount of polyamino cations completely neutralizes the anions of nucleic acid biomacromolecules, the amount of polyamino cations added is an additional 0.01% to 30% (m / v).

5. The polyamino cation complex according to claim 3, characterized in that, The nucleic acid biomolecules mentioned are one or more of DNA or its derivatives, RNA or its derivatives.

6. The polyamino cation complex according to claim 3, characterized in that, The polyamino cation refers to chitosan and / or ε-polylysine.

7. The polyamino cation complex according to claim 6, characterized in that, The ε-polylysine refers to a cationic ε-amino isomeric monomer polymer containing 25-30 lysine residues.

8. The polyamino cation complex according to claim 6, characterized in that, The chitosan is polyglucosamine (1-4)-2-amino-BD glucose or a derivative thereof.

9. The polyamino cation complex according to claim 3, characterized in that, The compounding process also includes a pH adjuster.

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