Film-forming type dairy cow nipple antibacterial agent based on macromolecule embedding technology and use method

Abstract

The invention relates to the technical field of antibacterial agents, and provides a film-forming type dairy cow nipple antibacterial agent based on a macromolecule embedding technology and a using method of the film-forming type dairy cow nipple antibacterial agent. The component A comprises a medicament microcapsule and a stabilizer; wherein the medicament microcapsule comprises a membrane material and a core material wrapped by the membrane material, and the core material comprises an antibacterial component and a film-forming agent; and the component B comprises a slow-release agent. According to the technical scheme, by improving the structure of the antibacterial agent, on one hand, the microcapsule structure can guarantee the activity of the drug, on the other hand, under the action of the component B, gradual slow release of the drug and the film-forming agent can be achieved, the antibacterial drug firstly acts on the surface of the nipple of the dairy cow, and then the film-forming agent forms a protective film to achieve the blocking effect.

Description

Technical Field

[0001] The invention relates to the technical field of antibacterial agents, and in particular to a film-forming cow nipple antibacterial agent based on polymer embedding technology and a use method thereof. Background Art

[0002] Cow mastitis is one of the common infectious diseases of dairy cows, causing serious economic losses to the dairy farming industry. Antibiotics are commonly used to treat mastitis in clinical practice, but excessive use of antibiotics can cause drug resistance in related pathogenic microorganisms. Using teat disinfectants to cut off the transmission pathway of pathogens is an effective method to prevent and control cow mastitis.

[0003] In the related technology, there is a method of disinfecting cow nipples by drug infiltration, but this method is complicated to operate; there is also a method of adding film-forming substances to antibacterial drugs to cut off the path of virus transmission, but the film-forming effect is not good and it is difficult to play an effective barrier role. Summary of the invention

[0004] In order to solve at least one of the above problems, the present invention provides a film-forming cow teat antibacterial agent based on polymer encapsulation technology, comprising separately preserved component A and component B; component A comprises agent microcapsules and a stabilizer; wherein the agent microcapsules comprise a film material and a core material wrapped by the film material, and the film material is PLGA; the core material comprises an antibacterial component and a film-forming agent; component B comprises a sustained-release agent, and the sustained-release agent is an aqueous sustained-release agent with a pH of 6-6.5.

[0005] In this technical solution, the antibacterial agent is divided into two independently preserved components, wherein component A is a microcapsule structure, in which a core material containing an antibacterial component is wrapped by a film material; the film material is hydrolyzed and ruptured under the action of a sustained-release agent to release the core material; the core material contains antibacterial components, which can achieve sterilization of cow nipples; further, the film-forming agent adheres to the cow nipples under the action of the sustained-release agent to form a protective film to isolate the spread of bacteria. In this technical solution, by improving the structure of the antibacterial agent, the microcapsule structure can ensure the activity of the drug on the one hand, and on the other hand, under the action of component B, the drug and the film-forming agent can be gradually released. The antibacterial drug first acts on the surface of the cow nipples, and then the film-forming agent forms a protective film to act as a barrier.

[0006] Furthermore, the pharmaceutical microcapsules are prepared by the following method: a drug solution is prepared according to the ratio of 120-150g PLGA, 10-20g antibacterial component, 30-40g film-forming agent, and 2-5L organic solvent; the drug solution is evenly dispersed, and a surfactant is added for ultrasonic emulsification treatment; then it is atomized into droplets through a spray device and enters a drying device; and the pharmaceutical microcapsules are dried, wherein the film material is PLGA.

[0007] Furthermore, the surfactant is polyvinyl alcohol; and / or the amount of surfactant added is 5-12g; and / or the organic solvent includes at least one of chloroform, dichloromethane, chloroform, and ethyl acetate; and / or in the ultrasonic emulsification treatment, the ultrasonic frequency is 25-40kHz, and the treatment time is 30-60min; and / or in the spray device, the spray rate of the drug solution is 1-1.5ml / h; and / or in the drying device, the drying temperature is controlled to be 20-30°C and the humidity is not more than 10%.

[0008] Furthermore, the antibacterial component includes at least one of honeysuckle extract, coptis chinensis extract, astragalus extract, forsythia suspensa extract, panax notoginseng extract, salvia miltiorrhiza extract, and angelica extract.

[0009] Honeysuckle contains a variety of natural compounds with broad-spectrum antibacterial, antiviral and anti-inflammatory effects. The main active ingredient in Coptis chinensis is berberine, which has significant antibacterial effects. Astragalus is widely used to improve immunity, antibacterial and antiviral, and has the function of enhancing the body's disease resistance. It can also regulate the body's immune response and prevent the spread of infection. Forsythia suspensa contains volatile oils, flavonoids and other ingredients. Panax notoginseng is believed to have anti-inflammatory, antibacterial and blood circulation promoting effects, and its extracts have potential in promoting local immunity and treating infections. Salvia miltiorrhiza has certain antibacterial effects, especially in antifungal and antiviral applications. Angelica extracts not only have a certain effect on antibacterial, but also help to improve the body's immunity and recovery ability. The active ingredients of these herbal extracts have antibacterial, antiviral and anti-inflammatory effects, and can work together on microorganisms to enhance the antibacterial activity of the agent. Combining them with polymer encapsulation technology makes the antibacterial components have a broader spectrum and more lasting antibacterial effect during the release process.

[0010] In this technical solution, by introducing various Chinese herbal extracts such as honeysuckle, coptis chinensis, astragalus and other ingredients with antibacterial properties into the medicament, a synergistic effect can be formed, which significantly enhances the antibacterial effect of the medicament, especially for common microorganisms such as bacteria, viruses and fungi, providing a broad-spectrum antibacterial ability. As a natural drug source, Chinese herbal extracts have lower toxic side effects and can reduce the risk of drug resistance compared with modern drugs. By adding various Chinese herbal extracts such as honeysuckle, coptis chinensis, astragalus and other extracts on the basis of polymer embedding technology, the present invention not only enhances the antibacterial effect of the antibacterial agent, but also improves the safety and biocompatibility of the drug, and at the same time prolongs the duration of the drug effect through sustained release and film-forming technology.

[0011] Furthermore, the film-forming agent is a film-forming component wrapped by PLGA; the film-forming component can polymerize in water to form a protective film.

[0012] Furthermore, the film-forming agent is prepared in the following manner: 100 g of polyol and 25-45 g of isocyanate are mixed, 0.5-1 g of catalyst is added, and the mixture is reacted at a temperature of 90-95° C. for 2-3 h to obtain a prepolymer; a reaction solution is prepared according to a ratio of 100 g of PLGA, 45-55 g of prepolymer, and 2-5 L of organic solvent; the reaction solution is atomized into droplets through a spray device and enters a drying device; and the film-forming agent is dried.

[0013] In this technical solution, the film-forming agent includes a film material and a core material, wherein the film material is PLGA and the core material is a polyurethane prepolymer. The PLGA film material is hydrolyzed and ruptured in an acidic environment, thereby releasing the polyurethane prepolymer inside, which can polymerize into a film when it encounters water, thereby adhering to the surface of the skin and playing a barrier role.

[0014] Therefore, the sustained-release agent is a weakly acidic aqueous sustained-release agent, and the pH value is preferably 6-6.5. Specifically, the sustained-release agent includes NaCl, KCl, Na 2 HPO 4 , KH 2 PO 4 , HCl; the sustained-release agent is prepared by the following method: 8-10 parts of NaCl, 0.1-0.5 parts of KCl, 1-2 parts of Na 2 HPO 4 , 0.1-0.5 parts KH 2 PO 4 Dissolve in 0.5-1L deionized water, stir well, and add HCl to adjust the pH to 6-6.5.

[0015] Further, in parts by mass, component A includes 60-70 parts of pharmaceutical microcapsules and 30-40 parts of stabilizers; the stabilizer is selected from glycerol or glycerol ether. Component A can be obtained by dispersing 60-70 parts of pharmaceutical microcapsules in 30-40 parts of stabilizers.

[0016] Furthermore, component A also includes 5-8 parts of disinfectant and 6-10 parts of dispersant in parts by mass; the disinfectant is selected from at least one of iodine tincture, hydrogen peroxide, and isopropyl alcohol; the dispersant is selected from at least one of Tween-20, Tween-40, Tween-60, and Tween-80.

[0017] The present invention also provides a method for using the above-mentioned antibacterial agent, comprising the following steps: Spray component A and component B on the teats of dairy cows in sequence; let stand to form a film.

[0018] The technical solution of the present invention can achieve at least one of the following beneficial effects: 1. By wrapping the antibacterial agent with PLGA membrane, the drug ingredients can be effectively protected from the influence of the external environment (such as oxidation, humidity, etc.), thereby improving the stability of the drug and extending the shelf life of the drug.

[0019] 2. The degradability of PLGA allows the drug and film-forming components to be gradually released in the body. The drug is used first to achieve the purpose of sterilization, and then the film-forming component achieves the barrier effect; ultimately forming a two-phase protection.

[0020] 3. High safety: PLGA, as a biodegradable material, can be degraded into non-toxic lactic acid and glycolic acid, has good biocompatibility, reduces the side effects of the drug system, and is suitable for long-term or repeated use of antibacterial treatment. DETAILED DESCRIPTION

[0021] In order to make the above-mentioned purposes, features and advantages of the present invention more obvious and easy to understand, the technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0022] The invention provides a film-forming cow teat antibacterial agent based on polymer embedding technology, comprising separately stored component A and component B; component A comprises agent microcapsules and a stabilizer; wherein the agent microcapsules comprise a film material and a core material wrapped by the film material, wherein the film material is PLGA; the core material comprises an antibacterial agent and a film-forming agent; component B comprises a sustained-release agent, and the sustained-release agent is an aqueous sustained-release agent with a pH value of 6-6.5.

[0023] In component A, the pharmaceutical microcapsule includes a membrane material and a core material wrapped in the membrane material. The membrane material is mainly composed of PLGA, and the core material is composed of an antibacterial component and a film-forming agent. PLGA is also known as polylactic-co-glycolic acid copolymer (poly(lactic-co-glycolic acid); it is polymerized from two monomers, lactic acid and glycolic acid, and has good biocompatibility and degradability, can effectively protect the internal antibacterial components, and control the release rate of the drug. Preferably, the proportion of lactic acid monomers in PLGA is 50-75%. The stabilizer is used to enhance the stability of the pharmaceutical microcapsule to ensure that it will not degrade or rupture during the preparation and storage process. The sustained-release agent is a weakly acidic aqueous solution. Under the action of the sustained-release agent, the degradation of the PLGA membrane material can be accelerated, so that the antibacterial components in the pharmaceutical microcapsule are released.

[0024] The preparation process of pharmaceutical microcapsules includes the following steps: Preparation of drug solution: 120-150g PLGA, 10-20g antibacterial component, 30-40g film-forming agent and 2-5L organic solvent are mixed in proportion to prepare a uniform drug solution. Ultrasonic emulsification treatment: Surfactant is added to the drug solution, and after ultrasonic emulsification treatment, the drug solution forms a uniform microemulsion state, which is conducive to the subsequent capsule formation. Spray drying: The emulsified drug solution is atomized into droplets through a spray device, and dried through a drying device to obtain pharmaceutical microcapsules.

[0025] Furthermore, the surfactant is polyvinyl alcohol; and / or the amount of surfactant added is 5-12g; and / or the organic solvent includes at least one of chloroform, dichloromethane, chloroform, and ethyl acetate; and / or in the ultrasonic emulsification treatment, the ultrasonic frequency is 25-40kHz, and the treatment time is 30-60min; and / or in the spray device, the spray rate of the drug solution is 1-1.5ml / h; and / or in the drying device, the drying temperature is controlled to be 20-30°C and the humidity is not more than 10%.

[0026] Furthermore, the antibacterial component includes at least one of honeysuckle extract, coptis chinensis extract, astragalus extract, forsythia suspensa extract, panax notoginseng extract, salvia miltiorrhiza extract, and angelica extract.

[0027] Honeysuckle contains a variety of natural compounds with broad-spectrum antibacterial, antiviral and anti-inflammatory effects. The main active ingredient in Coptis chinensis is berberine, which has significant antibacterial effects. Astragalus is widely used to improve immunity, antibacterial and antiviral, and has the function of enhancing the body's disease resistance. It can also regulate the body's immune response and prevent the spread of infection. Forsythia suspensa contains volatile oils, flavonoids and other ingredients. Panax notoginseng is believed to have anti-inflammatory, antibacterial and blood circulation promoting effects, and its extracts have potential in promoting local immunity and treating infections. Salvia miltiorrhiza has certain antibacterial effects, especially in antifungal and antiviral applications. Angelica extracts not only have a certain effect on antibacterial, but also help to improve the body's immunity and recovery ability. The active ingredients of these herbal extracts have antibacterial, antiviral and anti-inflammatory effects, and can work together on microorganisms to enhance the antibacterial activity of the agent. Combining them with polymer encapsulation technology makes the antibacterial components have a broader spectrum and more lasting antibacterial effect during the release process.

[0028] In this embodiment, by introducing various Chinese herbal extracts such as honeysuckle, coptis chinensis, astragalus membranaceus and other ingredients with antibacterial properties into the medicament, a synergistic effect can be formed, which significantly enhances the antibacterial effect of the medicament, especially for common microorganisms such as bacteria, viruses and fungi, providing a broad spectrum of antibacterial ability. As a natural drug source, Chinese herbal extracts have lower toxic side effects and can reduce the risk of drug resistance compared with modern drugs. By adding various Chinese herbal extracts such as honeysuckle, coptis chinensis, astragalus membranaceus on the basis of polymer embedding technology, the present invention not only enhances the antibacterial effect of the antibacterial component, but also improves the safety and biocompatibility of the drug, and at the same time prolongs the duration of the drug effect through sustained release and film-forming technology.

[0029] Furthermore, the film-forming agent is a film-forming component wrapped by PLGA; the film-forming component can polymerize in water to form a protective film.

[0030] Preferably, the film-forming agent is a polyurethane prepolymer, which is obtained by prepolymerizing polyol and isocyanate under the action of a catalyst. The PLGA film material is hydrolyzed and ruptured in an acidic environment, thereby releasing the internal polyurethane prepolymer, which can polymerize into a film when exposed to water, thereby adhering to the surface of the skin and playing a barrier role.

[0031] Furthermore, the film-forming agent is prepared in the following manner: 100 g of polyol and 25-45 g of isocyanate are mixed, 0.5-1 g of catalyst is added, and the mixture is reacted at a temperature of 90-95° C. for 2-3 h to obtain a prepolymer; a reaction solution is prepared according to a ratio of 100 g of PLGA, 45-55 g of prepolymer, and 2-5 L of organic solvent; the reaction solution is atomized into droplets through a spray device and enters a drying device; and the film-forming agent is dried.

[0032] Among them, the organic solvent includes at least one of chloroform, dichloromethane, chloroform, and ethyl acetate. It should be noted that in a specific embodiment, the organic solvents involved in the preparation process of the antibacterial agent are generally selected from the same type. In the spray device, the spray rate of the reaction liquid is 0.5-0.8ml / h; in the drying device, the drying temperature is controlled to be 20-30°C, and the humidity does not exceed 10%. In this embodiment, the reaction liquid is atomized into fine droplets by a spray device. After these droplets enter the drying device, the solvent will evaporate rapidly, leaving a solid film-forming substance. Thereby achieving PLGA encapsulation of the film-forming component.

[0033] The sustained-release agent is a weakly acidic aqueous sustained-release agent, and the pH value is preferably 6-6.5. Specifically, the sustained-release agent includes NaCl, KCl, Na 2 HPO 4 , KH 2 PO 4, HCl; the sustained-release agent is prepared by the following method: 8-10 parts of NaCl, 0.1-0.5 parts of KCl, 1-2 parts of Na 2 HPO 4 , 0.1-0.5 parts KH 2 PO 4 Dissolve in 0.5-1L deionized water, stir well, and add HCl to adjust the pH to 6-6.5.

[0034] Further, component A includes 60-70 parts of pharmaceutical microcapsules and 30-40 parts of stabilizers in parts by mass; the stabilizer is selected from glycerol or glycerol ether. The stabilizer is used to stabilize the pharmaceutical microcapsules to prevent degradation or failure during storage and use. Glycerol and glycerol ether are common stabilizers with good dispersibility and biocompatibility, and can effectively protect the integrity of the microcapsules.

[0035] Furthermore, component A further comprises 5-8 parts of disinfectant and 6-10 parts of dispersant in parts by mass; the disinfectant is selected from at least one of iodine tincture, hydrogen peroxide and isopropyl alcohol; the dispersant is selected from at least one of Tween-20, Tween-40, Tween-60 and Tween-80. Iodine tincture, hydrogen peroxide and isopropyl alcohol all have broad-spectrum antibacterial effects, can effectively kill microorganisms and have good disinfection effects. Tween dispersants (such as Tween-20, Tween-40, etc.) are non-ionic surfactants with good wetting, dispersing and emulsifying effects, which can optimize the stability of the solution.

[0036] The present invention also provides a method for using the above-mentioned antibacterial agent, comprising the following steps: Spray component A and component B on the teats of dairy cows in sequence; let stand to form a film.

[0037] Example 1

[0038] The present embodiment provides a film-forming cow nipple antibacterial agent based on polymer encapsulation technology, including separately stored component A and component B; component A includes agent microcapsules and stabilizers; wherein the agent microcapsules include a film material and a core material wrapped by the film material, and the film material is PLGA; the core material includes an antibacterial component and a film-forming agent; component B includes a sustained-release agent, and the sustained-release agent is an aqueous sustained-release agent with a pH of 6.

[0039] Preparation of Component A: 1. Mix 100g of polyol and 25g of isocyanate, add 0.5g of catalyst, and react at 90°C for 2h to obtain a prepolymer.

[0040] A reaction solution is prepared according to the ratio of 100 g PLGA, 45 g prepolymer and 2 L chloroform; the reaction solution is atomized into droplets through a spray device and enters a drying device; and a film-forming agent is obtained by drying.

[0041] In the spray device, the spray rate of the reaction liquid is 0.5 ml / h; in the drying device, the drying temperature is controlled to be 20° C. and the humidity is not more than 10%.

[0042] 2. Prepare a drug solution according to the ratio of 120 g PLGA, 10 g antibacterial component, 30 g film-forming agent and 2 L chloroform.

[0043] The drug solution was dispersed evenly, and 5 g of polyvinyl alcohol was added for ultrasonic emulsification treatment; the ultrasonic frequency was 25 kHz, and the treatment time was 30 min.

[0044] Then it is atomized into droplets through a spray device and enters a drying device; it is dried to obtain pharmaceutical microcapsules.

[0045] In the spray device, the spray rate of the drug solution is 1 ml / h; in the drying device, the drying temperature is controlled to be 20°C and the humidity is not more than 10%.

[0046] The antibacterial components include honeysuckle extract, coptis chinensis extract and astragalus extract.

[0047] 3. Disperse 60 g of the pharmaceutical microcapsules in 30 g of glycerol ether to obtain component A.

[0048] Preparation of component B: According to 8 parts NaCl, 0.1 parts KCl, 1 part Na 2 HPO 4 , 0.1 parts KH 2 PO 4 Dissolve in 0.5 L of deionized water, stir well, and add HCl to adjust the pH to 6.

[0049] Example 2

[0050] The present embodiment provides a film-forming cow teat antibacterial agent based on polymer encapsulation technology, comprising separately stored component A and component B; component A comprises agent microcapsules and a stabilizer; wherein the agent microcapsules comprise a film material and a core material wrapped by the film material, and the film material is PLGA; the core material comprises an antibacterial component and a film-forming agent; component B comprises a sustained-release agent, and the sustained-release agent is an aqueous sustained-release agent with a pH of 6.5.

[0051] Preparation of Component A: 1. Mix 100g of polyol and 45g of isocyanate, add 1g of catalyst, and react at 95°C for 3h to obtain a prepolymer.

[0052] A reaction liquid is prepared according to the ratio of 100 g PLGA, 55 g prepolymer and 5 L dichloromethane; the reaction liquid is atomized into droplets through a spray device and enters a drying device; and a film-forming agent is obtained by drying.

[0053] In the spray device, the spray rate of the reaction liquid is 0.8 ml / h; in the drying device, the drying temperature is controlled to be 30° C. and the humidity is not more than 10%.

[0054] 2. Prepare a drug solution according to the ratio of 150 g PLGA, 20 g antibacterial component, 40 g film-forming agent and 5 L dichloromethane.

[0055] The drug solution was dispersed evenly, and 12 g of polyvinyl alcohol was added for ultrasonic emulsification treatment; the ultrasonic frequency was 40 kHz, and the treatment time was 60 min.

[0056] Then it is atomized into droplets through a spray device and enters a drying device; it is dried to obtain pharmaceutical microcapsules.

[0057] In the spray device, the spray rate of the drug solution is 1.5 ml / h; in the drying device, the drying temperature is controlled to be 30°C and the humidity is not more than 10%.

[0058] The antibacterial components include: astragalus extract, forsythia extract, panax notoginseng extract, salvia miltiorrhiza extract, and angelica extract.

[0059] 3. Disperse 70 g of pharmaceutical microcapsules, 6 g of isopropanol, and 8 g of Tween-20 in 40 g of glycerol ether to obtain component A.

[0060] Preparation of component B: According to 10 parts NaCl, 0.5 parts KCl, 2 parts Na 2 HPO 4 , 0.5 parts KH 2 PO 4 Dissolve in 1 L of deionized water, stir well, and add HCl to adjust the pH to 6.5.

[0061] Example 3

[0062] The present embodiment provides a film-forming cow teat antibacterial agent based on polymer encapsulation technology, comprising separately stored component A and component B; component A comprises agent microcapsules and a stabilizer; wherein the agent microcapsules comprise a film material and a core material wrapped by the film material, and the film material is PLGA; the core material comprises an antibacterial component and a film-forming agent; component B comprises a sustained-release agent, and the sustained-release agent is an aqueous sustained-release agent with a pH of 6.5.

[0063] Preparation of Component A: 1. Mix 100g of polyol and 35g of isocyanate, add 0.8g of catalyst, and react at 92°C for 2h to obtain a prepolymer.

[0064] A reaction liquid is prepared according to the ratio of 100 g PLGA, 48 g prepolymer and 4 L ethyl acetate; the reaction liquid is atomized into droplets through a spray device and enters a drying device; and a film-forming agent is obtained by drying.

[0065] In the spray device, the spray rate of the reaction liquid is 0.6 ml / h; in the drying device, the drying temperature is controlled to be 26° C. and the humidity is not more than 10%.

[0066] 2. Prepare a drug solution according to the ratio of 140 g PLGA, 16 g antibacterial component, 35 g film-forming agent and 3 L ethyl acetate.

[0067] The drug solution was dispersed evenly, and 8 g of polyvinyl alcohol was added for ultrasonic emulsification treatment; the ultrasonic frequency was 30 kHz, and the treatment time was 50 min.

[0068] Then it is atomized into droplets through a spray device and enters a drying device; it is dried to obtain pharmaceutical microcapsules.

[0069] In the spray device, the spray rate of the drug solution is 1.2 ml / h; in the drying device, the drying temperature is controlled to be 28°C and the humidity is not more than 10%.

[0070] The antibacterial components include: honeysuckle extract, coptis extract, notoginseng extract, salvia miltiorrhiza extract, and angelica extract.

[0071] 3. Disperse 68 g of pharmaceutical microcapsules, 8 g of hydrogen peroxide and 6 g of Tween-60 in 37 g of glycerol to obtain component A.

[0072] Preparation of component B: According to 9 parts of NaCl, 0.4 parts of KCl, 1 part of Na 2 HPO 4 , 0.3 parts KH 2 PO 4 Dissolve in 1 L of deionized water, stir well, and add HCl to adjust the pH to 6.5.

[0073] Comparative Example 1 This comparative example provides an antibacterial agent for cow nipples. The specific structure and preparation process refer to Example 1, except that the sustained-release agent is deionized water.

[0074] Comparative Example 2 This comparative example provides an antibacterial agent for cow nipples. The specific structure and preparation process refer to Example 1, except that no film-forming agent is added.

[0075] The antibacterial agents provided in Examples 1-3 and Comparative Examples 1-2 were tested for antibacterial performance and film-forming performance.

[0076] 1. Antibacterial performance: 20 dairy cows with similar age, body shape and physiological condition were selected and randomly divided into 5 groups. Their nipples were sprayed with the above 5 antibacterial agents (spraying method: spraying component A and component B at one time); samples were taken for culture 2 hours later, and the antibacterial rate was calculated. The results are shown in Table 1.

[0077] 2. Film-forming performance: Use the above five antibacterial agents and spray them onto the silicone surface in the order of component A first and then component B (spraying time interval is 10s); observe the film-forming time. The results are shown in Table 1.

[0078] Table 1

[0079] In comparative example 1, since deionized water was selected as the sustained-release agent, the hydrolysis rate of the membrane material was slowed down, thereby affecting the film-forming time. In comparative example 2, since no film-forming agent was added, the antibacterial agent could not form a film, thereby affecting the antibacterial rate.

[0080] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A film-forming cow nipple antibacterial agent based on polymer embedding technology, characterized in that: comprising component A and component B which are stored separately; The component A includes pharmaceutical microcapsules and stabilizers; Wherein, the drug microcapsule comprises a membrane material and a core material wrapped by the membrane material, wherein the membrane material is PLGA; the core material comprises an antibacterial component and a film-forming agent; The component B comprises a sustained-release agent, which is an aqueous sustained-release agent with a pH value of 6-6.

5.

2. The film-forming cow teat antibacterial agent according to claim 1, characterized in that: The pharmaceutical microcapsules are prepared by the following method: A drug solution is prepared according to the ratio of 120-150 g PLGA, 10-20 g antibacterial component, 30-40 g film-forming agent, and 2-5 L organic solvent; The drug solution is dispersed uniformly, and a surfactant is added to perform ultrasonic emulsification treatment; then the drug solution is atomized into droplets through a spray device and enters a drying device; The pharmaceutical microcapsules are obtained by drying.

3. The film-forming cow teat antibacterial agent according to claim 2, characterized in that: The surfactant is polyvinyl alcohol; and / or The amount of surfactant added is 5-12g; and / or The organic solvent comprises at least one of chloroform, dichloromethane, chloroform and ethyl acetate; and / or In the ultrasonic emulsification treatment, the ultrasonic frequency is 25-40kHz and the treatment time is 30-60min; and / or In the spray device, the spray speed of the drug solution is 1-1.5 ml / h; and / or In the drying device, the drying temperature is controlled to be 20-30° C. and the humidity is controlled not to exceed 10%.

4. The film-forming cow teat antibacterial agent according to claim 3, characterized in that: The antibacterial component comprises at least one of honeysuckle extract, coptis chinensis extract, astragalus extract, forsythia suspensa extract, notoginseng extract, salvia miltiorrhiza extract and angelica extract.

5. The film-forming cow teat antibacterial agent according to any one of claims 2 to 4, characterized in that: The film-forming agent is a film-forming component wrapped by PLGA; the film-forming component can polymerize in water to form a protective film.

6. The film-forming cow teat antibacterial agent according to claim 5, characterized in that: The film-forming agent is prepared by the following method: Mix 100g of polyol and 25-45g of isocyanate, add 0.5-1g of catalyst, and react at 90-95°C for 2-3h to obtain a prepolymer; A reaction solution is prepared according to the ratio of 100 g PLGA, 45-55 g prepolymer, and 2-5 L organic solvent; The reaction liquid is atomized into liquid droplets through a spray device and enters a drying device; and the film-forming agent is obtained by drying.

7. The film-forming cow teat antibacterial agent according to claim 1, characterized in that: The sustained-release agent includes NaCl, KCl, Na2HPO4, KH2PO4, and HCl; The sustained-release agent is prepared by the following method: Take 8-10 parts of NaCl, 0.1-0.5 parts of KCl, 1-2 parts of Na2HPO4, and 0.1-0.5 parts of KH2PO4 by mass, dissolve them in 0.5-1L of deionized water, stir evenly, and add HCl to adjust the pH to 6-6.

5.

8. The film-forming cow teat antibacterial agent according to claim 1, characterized in that: In terms of weight, the component A includes 60-70 parts of pharmaceutical microcapsules and 30-40 parts of stabilizers; The stabilizer is selected from glycerol or glycerol ether.

9. The film-forming cow teat antibacterial agent according to claim 7, characterized in that: In terms of parts by mass, the component A further comprises 5-8 parts of a disinfectant and 6-10 parts of a dispersant; The disinfectant is selected from at least one of iodine tincture, hydrogen peroxide, and isopropyl alcohol; The dispersant is selected from at least one of Tween-20, Tween-40, Tween-60 and Tween-80.

10. The method for using the antibacterial agent according to any one of claims 1 to 9, characterized in that: The following steps are involved: Spray component A and component B on the teats of dairy cows in sequence; let stand to form a film.

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