A teat sealant for the prevention and treatment of mastitis in dry cows and a method of preparation

Abstract

This invention discloses a teat sealant and its preparation method for preventing and treating mastitis during the dry period in dairy cows, belonging to the field of veterinary drug formulation technology. The components and their mass percentages in the teat sealant are as follows: 45-70% non-toxic metal compound, 0.2-6% bactericide, 1-10% thickener, 1-15% organosilicon surfactant, with the remainder being a carrier. The teat sealant of this invention can significantly improve the cure rate of mastitis during the dry period in dairy cows, effectively improve the problem of milk leakage in high-producing cows, improve the paste texture, kill pathogens, increase color for better identification, and leave no drug residue after the dry period. It is a functional teat sealant product for preventing and treating mastitis during the dry period in dairy cows, with broad clinical application prospects.

Description

Technical Field

[0001] This invention belongs to the field of veterinary drug formulation technology, specifically relating to a teat sealant for preventing and treating mastitis in dairy cows during the dry period and its preparation method. Background Technology

[0002] Bovine mastitis is one of the most devastating diseases affecting the dairy industry worldwide, causing $200 million annually in the United States alone. Subclinical mastitis, in particular, is prevalent and difficult to detect in herds. Staphylococcus aureus, Streptococcus, and Escherichia coli are reportedly major pathogens causing bovine mastitis. These mastitis-causing microorganisms infect mammary tissue, leading to inflammation. Clinical prevention and treatment primarily involve mammary instillation of medication. However, this method, where the syringe dilates the teat ducts, easily introduces microorganisms into the udder. These pathogens then enter the mammary tissue through the teat ducts and proliferate, directly affecting the function of the milk-producing tissue and causing mastitis.

[0003] The dry period for dairy cows refers to the time between two consecutive lactation periods, usually lasting 50-70 days. During this period, cows do not produce milk, and it is a time for mammary tissue recovery and regeneration. Therefore, the dry period is the optimal time for treating mastitis and a crucial stage for preventing infection. Reports indicate that 65% of clinical mastitis cases in lactating cows are related to infection during the dry period, and the risk of developing new mastitis during the dry period is 10 times higher than during lactation. One week after the dry period, more than 40% of teat pores have not formed keratin plugs, and six weeks after the dry period, more than 20% of teat pores remain open. Open teat pores provide a favorable channel for pathogen invasion, significantly increasing the risk of mastitis infection.

[0004] Because dairy cows in late pregnancy are not given preventative medication after milking stops, the probability of mammary gland infection is high, accounting for 53% of mastitis cases during lactation. Furthermore, in the current context of cost reduction, efficiency improvement, and antibiotic restriction, selective dry-off saves economic and labor costs. A study conducted at the University of Minnesota showed that selective dry-off can save $2-3 per head (approximately 13.6-20.4 yuan per head). Many developed countries have adopted selective dry-off. Since 2019, 20% of dairy farms in the UK have implemented selective dry-off treatment, and whole-herd dry-off treatment will be officially banned from 2022. Since 2014, selective dry-off treatment has been used in over 98% of cases in Norway, 93%-94% in Denmark, and 87% in Finland in 2018. With the EU Regulation 2019 / 6 banning the prophylactic use of antibiotics coming into effect in 2022, the EU has completely banned whole-herd dry-off treatment for every dairy cow. Studies have found that using antibacterial drug injections in combination with nipple sealants during the dry period reduces the incidence of subclinical mastitis by 37% compared to using antibacterial drug injections alone. However, this approach is prone to problems such as drug resistance, severe irritation, drug residues, and secondary inflammatory reactions. As a result, farms have an increasing demand for antibiotic-free, functional sealants.

[0005] Among the publicly disclosed patents and technologies, patent CN101439044A uses a gel formulation that lacks a sealing effect, has a short duration of action, and cannot provide long-term protection during the dry period; patent CN111840212A uses a phase change-sensitive in-situ gel technology, while adding 0.02-0.8% chitosan as a gel enhancer to slow down gel erosion and increase the duration of action, solving the problem of long-term effectiveness, but the amount of chitosan added is too small to provide any health-promoting functional effects; CN104644670A uses geniposide and bismuth subnitrate in combination to address the problem of inflammatory reactions during the dry period caused by environmental pathogens and bacterial endotoxins, such as redness, swelling, heat, and pain in the mammary glands, but the process only involves micronization of the raw materials, resulting in poor formulation stability. Existing technologies do not describe solutions for common mammary gland infections in high-producing dairy cows using dry period sealing agents.

[0006] Therefore, this invention provides a teat sealant solution suitable for dry-life management in dairy farms, focusing on teat sterilization and disinfection while enhancing drug identification. To this end, the applicant has developed a novel teat sealant that not only kills pathogens but also leaves no residue through color-coding and promptly seals open milk ducts. Summary of the Invention

[0007] The present invention aims to solve the technical problems in the prior art and provide a teat sealant for preventing mastitis in dairy cows during the dry period and its preparation method.

[0008] To achieve the above objectives, the specific technical solution of the present invention is as follows:

[0009] This invention provides a teat sealant for preventing mastitis in dairy cows during the dry period. The teat sealant is composed of: a non-toxic metal compound, a bactericide, a thickener, an organosilicon surfactant, and a carrier.

[0010] The components and their mass percentages in the nipple sealant are as follows: 45-70% non-toxic metal compound, 0.2-6% bactericide, 1-10% thickener, 1-15% organosilicon surfactant, and the remainder is carrier.

[0011] Preferably, the components and their mass percentages in the nipple sealant are as follows: 65% non-toxic metal compound, 0.5-5% bactericide, 2-5% thickener, 2-10% organosilicon surfactant, and the remainder is a carrier.

[0012] More preferably, the components and their mass percentages in the nipple sealant are as follows: 65% non-toxic metal compound, 1% bactericide, 2.4% thickener, 7.6% organosilicon surfactant, and 24% carrier.

[0013] The non-toxic metal compound is one or more of basic bismuth nitrate, titanium dioxide, zinc oxide, and zinc sulfide, preferably basic bismuth nitrate.

[0014] The bactericide is one or more of chlorhexidine, povidone-iodine, lactic acid, sodium hypochlorite, benzalkonium bromide, glycolic acid, and organic acids, preferably povidone-iodine.

[0015] The thickener is one or more of aluminum distearate, aluminum stearate, cetearyl alcohol, and aluminum di / tristearate, preferably aluminum di / tristearate.

[0016] The organosilicon surfactant is one or more of the following: polydimethylsiloxane crosslinked polymer, vinyl polydimethylsiloxane crosslinked polymer, cyclopentadimethylsiloxane, PEG-10 polydimethylsiloxane, distearate dimethylammonium lithium montmorillonite, and cetyl polydimethylsiloxane.

[0017] Preferably, the organosilicon surfactant is one of polydimethylsiloxane crosslinked polymer, vinyl polydimethylsiloxane crosslinked polymer, and cetyl polydimethylsiloxane.

[0018] More preferably, the organosilicon surfactant is a polydimethylsiloxane crosslinked polymer.

[0019] The carrier is one or more of liquid paraffin, soybean oil for injection, peanut oil, castor oil, and medium-chain triglycerides, preferably liquid paraffin.

[0020] A preferred formulation is as follows: the components and their mass ratios in the nipple sealant are: 65% basic bismuth nitrate, 1% povidone-iodine, 2.4% aluminum di / tristearate, 7.6% polydimethylsiloxane crosslinked polymer, and 24% liquid paraffin.

[0021] This invention also provides a method for preparing a teat sealant for preventing mastitis in dairy cows during the dry period, the specific steps of which are as follows:

[0022] (1) Disperse the thickener and silicone surfactant in the carrier in the prescribed amount, control the temperature at 80℃~110℃, and mix evenly to obtain the matrix for later use;

[0023] (2) Disperse the bactericide and non-toxic metal compound in the matrix while stirring. After thorough mixing, use high shear technology.

[0024] (3) Dispense and seal, then sterilize by irradiation to obtain the nipple sealant product.

[0025] Beneficial effects:

[0026] 1. The active ingredient in the nipple sealant of this invention, basic bismuth nitrate, has astringent and mucosal protective effects, acting as a keratin plug to ensure the nipple sealing effect. Furthermore, the addition of polydimethylsiloxane cross-linked polymer enhances the spreadability of the formulation, making the cream silky, and strengthens the moisturizing effect, preventing shrinkage caused by the evaporation of volatile oils.

[0027] 2. The nipple sealant described in this invention is a suspension ointment. The addition of povidone-iodine can kill pathogens after use, preventing bacteria from entering the mammary gland through the nipple orifice and nipple duct and damaging the lactation function. It can maintain the sterility of the milk pool during the dry period. At the same time, povidone-iodine is also colored, which makes it easy for milkers to identify after the dry period, and will not cause contamination of pipelines and large vats of milk.

[0028] 3. The nipple sealant preparation method of the present invention adopts high shear technology, which has a high utilization rate of effective ingredients and makes the ointment more stable. It will not cause layering or oil leakage, resulting in uneven drug administration, causing the drug to break into fragments under the action of external force on the nipple, resulting in displacement and difficulty in squeezing out.

[0029] 4. The teat sealant of the present invention can kill pathogens and significantly reduce the incidence of mastitis in dairy cows during the dry period; and there is no drug residue after the dry period ends. It is a functional teat sealant product for the prevention and treatment of mastitis in dairy cows during the dry period. Detailed Implementation

[0030] The above content will be further described in detail below through specific embodiments. However, this should not be construed as limiting the scope of the above subject matter to the following embodiments. All technologies implemented based on the content of this invention fall within the scope.

[0031] Example 1

[0032] A teat sealant for preventing mastitis in dairy cows during the dry period, comprising the following components and their amounts: 65 parts basic bismuth nitrate, 0.5 parts povidone-iodine, 2 parts aluminum di / tristearate, 2 parts vinyl polydimethylsiloxane crosslinking polymer, and 30.5 parts liquid paraffin. The preparation steps are as follows:

[0033] (1) Disperse the prescribed amount of aluminum di / tristearate and vinyl polydimethylsiloxane crosslinking polymer evenly in the carrier, control the temperature at 80℃~110℃, and mix evenly to obtain the matrix for later use.

[0034] (2) Disperse povidone-iodine and basic bismuth nitrate in the matrix while stirring. After thorough mixing, use high shear technology.

[0035] (3) Dispense and seal, then sterilize by irradiation to obtain the nipple sealant product.

[0036] Example 2

[0037] A teat sealant for preventing mastitis in dairy cows during the dry period, comprising the following components and their amounts: 65 parts basic bismuth nitrate, 0.5 parts povidone-iodine, 2 parts aluminum di / tristearate, 2 parts polydimethylsiloxane crosslinked polymer, and 30.5 parts liquid paraffin. The preparation steps are as described in Example 1.

[0038] Example 3

[0039] A teat sealant for preventing mastitis in dairy cows during the dry period, comprising the following components and their amounts: 65 parts basic bismuth nitrate, 1 part povidone-iodine, 2.4 parts aluminum di / tristearate, 7.6 parts polydimethylsiloxane crosslinked polymer, and 24 parts liquid paraffin. The preparation steps are as described in Example 1.

[0040] Example 4

[0041] A teat sealant for preventing mastitis in dairy cows during the dry period, comprising the following components and their amounts: 65 parts basic bismuth nitrate, 5 parts povidone-iodine, 5 parts aluminum di / tristearate, 10 parts polydimethylsiloxane crosslinked polymer, and 15 parts liquid paraffin. The preparation steps are as described in Example 1.

[0042] Example 5

[0043] A teat sealant for preventing mastitis in dairy cows during the dry period, comprising the following components and their amounts: 65 parts basic bismuth nitrate, 5 parts povidone-iodine, 5 parts aluminum di / tristearate, 10 parts cetyl polydimethylsiloxane, and 15 parts liquid paraffin. The preparation steps are as described in Example 1.

[0044] Example 6

[0045] A teat sealant for preventing mastitis in dairy cows during the dry period, comprising the following components and their amounts: 65 parts basic bismuth nitrate, 1 part povidone-iodine, 2.4 parts aluminum di / tristearate, and 31 parts liquid paraffin. The preparation steps are as described in Example 1.

[0046] Example 7

[0047] A teat sealant for preventing mastitis in dairy cows during the dry period, comprising the following components and their amounts: 65 parts basic bismuth nitrate, 1 part povidone-iodine, 2.4 parts aluminum stearate, 7.6 parts distearate dimethylammonium lithium montmorillonite, and 24 parts liquid paraffin. The preparation steps are as described in Example 1.

[0048] Example 8

[0049] A teat sealant for preventing mastitis in dairy cows during the dry period, comprising the following components and their amounts: 65 parts basic bismuth nitrate, 1 part povidone-iodine, 2.4 parts aluminum di / tristearate, 7.6 parts cyclopentamethoxysiloxane, and 24 parts liquid paraffin. The preparation steps are as described in Example 1.

[0050] Example 9

[0051] A teat sealant for preventing mastitis in dairy cows during the dry period, comprising the following components and their amounts: 65 parts basic bismuth nitrate, 1 part chlorhexidine, 2.4 parts cetearyl alcohol, 7.6 parts PEG-10 polydimethylsiloxane, and 24 parts soybean oil for injection. The preparation steps are as described in Example 1.

[0052] Experimental Example 1: Trait Detection Experiment

[0053] The teat sealants used in Examples 1-9 for the prevention and treatment of bovine mastitis were placed at 60°C and high humidity (92.5% RH) for 10 days, and samples were taken for testing. The results showed that the teat sealants in Examples 1-5 and Examples 7-9 for the prevention and treatment of bovine mastitis had good viscosity and paste texture, no obvious layering, maintained a brown paste appearance, exhibited good spreadability, and showed little change in content. Compared to Examples 7-9, the addition of the organosilicon surfactant in Examples 1-5 better enhanced the spreadability of the formulation, and the paste had better moisturizing effects, with the oily carrier less prone to evaporation. The teat sealant without the surfactant of this invention (the product of Example 6) showed layering and lacked spreadability. Therefore, the organosilicon surfactant of this invention not only has anti-seepage and thickening effects but also enhances the spreadability of the formulation.

[0054] Table 1. Tests for phenotypic characteristics

[0055]

[0056] Experiment Example 2: Antibacterial Effect Experiment

[0057] Using Staphylococcus aureus, Escherichia coli, and Streptococcus agalactiae as test strains, microbial tests were conducted on Examples 3 and 9, and the control group (containing the antibiotic benzathine cloxacillin intravenous injection) under different conditions. The inhibition zone was measured using the agar diffusion method, and the results are shown in the table below.

[0058] Table 2 Antibacterial effect detection

[0059]

[0060] By comparing the microbiological tests of Examples 3 / 9 and the control group, the results showed that the nipple sealant of Examples 3 / 9 could kill Staphylococcus aureus, Escherichia coli and Streptococcus. However, Example 9 only killed Escherichia coli after being exposed to high temperature. Under accelerated conditions of 50℃-10d and 60℃-10d, the pathogens in the control group were not killed. Moreover, the control group was only effective against pathogens at room temperature, and the inhibition zone was significantly smaller than that of Example 3. It can be seen that the sealant of Example 3 of the present invention has higher stability and can still achieve the purpose of sterilization under extreme conditions for a long time.

[0061] Trial Example 3: Clinical Efficacy Trial

[0062] Experimental Protocol: A clinical trial was conducted at a ranch in Hebei Province. 120 dry-stage dairy cows with similar physical conditions were selected as subjects and divided into four groups of 30 cows each. After the last milking, the teats were cleaned and disinfected before administering the drug. The test drug was injected into each teat orifice. Somatic cell counts in milk samples were measured after milking of each group, and teat leakage was observed. The post-treatment somatic cell count and incidence of subclinical mastitis were also measured. The results are shown in the table below.

[0063] Table 3. Somatic cell count results from clinical trials of bovine teat sealants.

[0064]

[0065] Table 4. Clinical trial results of mastitis incidence in dairy cows treated with teat sealant.

[0066]

[0067] The clinical trial results above show that the nipple sealants of Examples 1, 3, and 5 of this invention, compared with the control group with added antibiotics, have a better sealing effect, effectively preventing the invasion of pathogens and killing pathogens, resulting in a lower incidence of mastitis, effectively improving the clinical cure rate, and alleviating the inflammatory response of clinical mastitis. Example 3, in particular, has the best effect. Somatic cell count (SCC) is the largest factor reflecting whether the body is infected, and it also affects milk quality. The higher the somatic cell count, the greater the possibility of infection by pathogens in the breast, and the higher the potential risk of disease. The nipple sealant of this invention can effectively reduce the somatic cell count in milk and improve the cure rate. Moreover, after the dry period, the milk is squeezed out in brown color, which is easy to identify and will not contaminate the large tank of milk, thus ensuring the quality of the milk.

Claims

1. A teat sealant for preventing mastitis in dairy cows during the dry period, characterized in that, The nipple sealant consists of: a non-toxic metal compound, a bactericide, a thickener, an organosilicon surfactant, and a carrier.

2. The nipple sealant according to claim 1, characterized in that, The components and their mass percentages in the nipple sealant are as follows: 45-70% non-toxic metal compound, 0.2-6% bactericide, 1-10% thickener, 1-15% organosilicon surfactant, and the remainder is carrier.

3. The nipple sealant according to claim 2, characterized in that, The components and their mass percentages in the nipple sealant are as follows: 65% non-toxic metal compound, 0.5-5% bactericide, 2-5% thickener, 2-10% organosilicon surfactant, and the remainder is carrier.

4. The nipple sealant according to any one of claims 1-3, characterized in that, The non-toxic metal compound is one or more of basic bismuth nitrate, titanium dioxide, zinc oxide, and zinc sulfide.

5. The nipple sealant according to any one of claims 1-3, characterized in that, The bactericide is one or more of chlorhexidine, povidone-iodine, lactic acid, sodium hypochlorite, benzalkonium bromide, glycolic acid, and organic acids.

6. The nipple sealant according to any one of claims 1-3, characterized in that, The thickener is one or more of aluminum distearate, aluminum stearate, cetearyl alcohol, and aluminum di / tristearate.

7. The nipple sealant according to any one of claims 1-3, characterized in that, The organosilicon surfactant is one or more of the following: polydimethylsiloxane crosslinked polymer, vinyl polydimethylsiloxane crosslinked polymer, cyclopentadimethylsiloxane, PEG-10 polydimethylsiloxane, distearate dimethylammonium lithium montmorillonite, and cetyl polydimethylsiloxane.

8. The nipple sealant according to claim 7, characterized in that, The organosilicon surfactant is one of polydimethylsiloxane crosslinked polymer, vinyl polydimethylsiloxane crosslinked polymer, and cetyl polydimethylsiloxane.

9. The nipple sealant according to any one of claims 1-3, characterized in that, The carrier is one or more of liquid paraffin, soybean oil for injection, peanut oil, castor oil, and medium-chain triglycerides.

10. A method for preparing a teat sealant for preventing mastitis in dairy cows during the dry period, as described in any one of claims 1-3, comprising the following steps: (1) Disperse the thickener and silicone surfactant in the carrier in the prescribed amount, control the temperature at 80℃~110℃, and mix evenly to obtain the matrix for later use; (2) Disperse the bactericide and non-toxic metal compound in the matrix while adding and stirring. After thorough mixing, use high shear technology. (3) Dispense and seal, then sterilize by irradiation to obtain the nipple sealant product.

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