CN114404356A - Temperature-sensitive type slow-release drug-loaded gel preparation for preventing and treating cow endometritis and preparation method thereof - Google Patents
Temperature-sensitive type slow-release drug-loaded gel preparation for preventing and treating cow endometritis and preparation method thereof Download PDFInfo
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- CN114404356A CN114404356A CN202210053250.6A CN202210053250A CN114404356A CN 114404356 A CN114404356 A CN 114404356A CN 202210053250 A CN202210053250 A CN 202210053250A CN 114404356 A CN114404356 A CN 114404356A
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Abstract
The invention relates to a temperature-sensitive slow-release drug-loaded gel preparation for preventing and treating cow endometritis and a preparation method thereof, and the preparation method comprises a temperature-sensitive gel carrier which is used for carrying drugs and is solidified into gel at a physiological temperature of being liquid at 0-10 ℃, wherein the gel carrier is coated with antibacterial, anti-inflammatory and/or repair-promoting drugs, and is a solution mainly prepared by mixing chitosan, hyaluronic acid, collagen, methylcellulose and poloxamer. The preparation method is simple, the prepared preparation realizes the injectability during administration and the solidification after administration, improves the retention efficiency and the retention time of the medicine in the uterus of the dairy cow, realizes the slow release function of the medicine, overcomes the problem that the traditional administration mode needs repeated administration, and further improves the treatment effect.
Description
Technical Field
The invention relates to a medicament for treating cow endometritis, in particular to a temperature-sensitive type slow-release drug-loaded gel preparation for preventing and treating cow endometritis and a preparation method thereof.
Background
The cow endometritis is the most common cow reproductive disease and is a more common clinical reproductive organ disease, and has the characteristics of high morbidity and difficult cure. The disease seriously threatens the normal growth and the normal reproduction of the dairy cows and is one of 4 major reproductive disorder diseases of the dairy cow breeding industry. The prevalence of endometritis is the major cause of lifelong infertility in cows. The breeding quality of the cow group is seriously influenced, the milk yield of the cow is also influenced, the treatment cost, the breeding cost and the like are increased, and farmers suffer great economic loss and seriously influence the development of the cow industry. In recent years, the incidence of endometritis of cows is increasing, and great pressure is brought to cow breeding, particularly mating work. More than 60 percent of the infertility of the cows in China is caused by endometritis, and the economic loss caused by the endometritis reaches about 30 hundred million RMB.
According to the traditional treatment of the cow endometritis, two modes of local uterine treatment and systemic treatment can be adopted according to the incidence characteristics and the influence range of the cow endometritis. Systemic treatment is usually applied to cows with systemic symptoms, such as fever, systemic inflammation, etc. The local uterine treatment is usually performed by irrigating with uterine irrigation solution or by administering drugs or microorganisms to the uterus. The commonly used uterine lavage liquid comprises antibiotics, disinfectant water, traditional Chinese medicines and the like. The lavage liquid usually exists in a liquid form, the uterus retention rate after lavage is low, the lavage is usually repeatedly carried out for a plurality of times, and the treatment is continuously carried out for 5-7 times, so that a certain treatment effect can be shown, the operation is complicated, the large-scale implementation is difficult, and the repeated lavage can easily cause the drug resistance of the dairy cow to the specific treatment, so that the treatment effect is reduced.
Disclosure of Invention
Aiming at the existing defects, the invention provides a temperature-sensitive type slow-release drug-loaded gel preparation for preventing and treating cow endometritis and a preparation method thereof.
The technical scheme adopted by the invention for solving the technical problems is as follows: a temperature-sensitive slow-release medicine-carrying gel preparation for preventing and treating cow endometritis comprises a temperature-sensitive gel carrier which is used for carrying medicine and is solidified into gel at a physiological temperature of being in a liquid state at a temperature of 0-10 ℃, the gel carrier is coated with antibacterial, anti-inflammatory and/or repair-promoting medicines, and the gel carrier is a solution mainly prepared by mixing chitosan, hyaluronic acid, collagen, methylcellulose and poloxamer.
Preferably, the medicine comprises antibiotics, traditional Chinese medicine extracts and hormones.
Preferably, the antibiotic is one or more of terramycin alkali, aureomycin, penicillin, tetracycline, erythromycin, fluoroquinolone drugs and sulfanilamide drugs, the traditional Chinese medicine extract is the extract of any of safflower, motherwort, catalpol, stachydrine, trichosanthes root, baicalin, berberine, honeysuckle, angelica dahurica, Chinese violet, catechu, Chinese pulsatilla root, dahurian patrinia herb and sargentgloryvine stem, and the hormone is one or more of prostaglandin, dexamethasone and cephalosporins.
Preferably, the weight percentages of the chitosan, the hyaluronic acid, the collagen, the methylcellulose and the poloxamer in the solution are 1.5-2.2%, 0.05-5%, 0.5-3%, 1.5-2.2% and 5-20% in sequence.
A preparation method of a temperature-sensitive type slow-release drug-loaded gel preparation for preventing and treating cow endometritis is characterized by comprising the following steps,
s1, preparing a gel carrier solution, namely mixing chitosan, hyaluronic acid, collagen, methylcellulose and poloxamer in proportion at the temperature of 0-10 ℃ to prepare the gel carrier solution, and sterilizing and disinfecting the gel carrier solution;
s2, encapsulating antibacterial, anti-inflammatory and/or repair promoting drugs in the gel carrier solution, preparing the drugs into a drug solution by using 0.9% of normal saline or water for injection, sterilizing, adding the drug solution into the gel carrier solution at 0-10 ℃, uniformly mixing to form a preparation, and sterilizing;
s3, packaging and storing the preparation, subpackaging the preparation in a sterile centrifuge tube or an injector, and storing at the temperature of 0-10 ℃.
Preferably, the medicine comprises antibiotics, traditional Chinese medicine extracts and hormones.
Preferably, the antibiotic is one or more of terramycin alkali, aureomycin, penicillin, tetracycline, erythromycin, fluoroquinolone drugs and sulfanilamide drugs, the traditional Chinese medicine extract is the extract of any of safflower, motherwort, catalpol, stachydrine, trichosanthes root, baicalin, berberine, honeysuckle, angelica dahurica, Chinese violet, catechu, Chinese pulsatilla root, dahurian patrinia herb and sargentgloryvine stem, and the hormone is one or more of prostaglandin, dexamethasone and cephalosporins.
Preferably, the weight percentages of the chitosan, the hyaluronic acid, the collagen, the methylcellulose and the poloxamer in the gel carrier solution are 1.5-2.2%, 0.05-5%, 0.5-3%, 1.5-2.2% and 5-20% in sequence.
Preferably, the preparation of the gel carrier solution, the drug solution, the preparation of the preparation and the packaging and storage of the preparation are all carried out at a temperature of 4 ℃.
The invention has the beneficial effects that: the preparation method is simple, the prepared preparation realizes the injectability during administration and the solidification after administration, and the liquid state is kept at low temperature, thereby facilitating the administration; after reaching the administration part, the gel is subjected to phase transition to form solid-semisolid gel due to the change of the temperature of the administration part, is easier to adhere to the uterus of the dairy cow and is not easy to run off, has a slow release effect while improving the local drug concentration of the affected part, overcomes the problems of repeated administration, low drug retention rate, drug resistance caused by repeated administration and the like of the traditional treatment method, improves the retention efficiency and retention time of the drug in the uterus of the dairy cow, further improves the treatment effect, reduces the treatment cost and the treatment period, reduces the workload of farm culturists, and reduces the elimination rate of the dairy cow.
Drawings
FIG. 1 is a state diagram of an embodiment of the present invention at different temperatures;
FIG. 2 is a graph of the sustained release effect of a formulation of the present invention after use;
FIG. 3 is a graph of the therapeutic effect of an embodiment of the present invention;
Detailed Description
To more clearly illustrate the objects, technical solutions and advantages of the embodiments of the present invention, the present invention will be further described with reference to the following embodiments, which are clearly and completely described, and it is obvious that the described embodiments are some, but not all embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments of the present invention without inventive step, are within the scope of the present invention.
In the invention, as shown in figure 1, a temperature-sensitive type slow-release drug-loaded gel preparation for preventing and treating cow endometritis and a preparation method thereof comprise the following steps: is carried out at a temperature of 4 ℃ and,
s1, preparing a gel carrier solution, namely mixing chitosan, hyaluronic acid, collagen, methylcellulose and poloxamer in proportion to prepare the gel carrier solution, and sterilizing and disinfecting the gel carrier solution; the gel carrier solution is in a liquid state at the temperature of 4 ℃, and is in a solid-semisolid gel state at the physiological temperature (37 ℃), namely at the temperature of a human body or an animal body, the gel carrier solution is in a phase change solidification state at the physiological temperature, namely at the temperature of the human body or the animal body, wherein the weight percentages of the chitosan, the hyaluronic acid, the collagen, the methylcellulose and the poloxamer in the solution are 1.5-2.2%, 0.05-5%, 0.5-3%, 1.5-2.2% and 5-20% in sequence, and preferably, the concentrations of the chitosan, the hyaluronic acid, the collagen, the methylcellulose and the poloxamer in the solution are 2%, 3.5%, 0.5%, 2% and 10% in sequence; the sterilization and disinfection are realized by irradiation, filtration, high-pressure steam sterilization or aseptic process control, if the solution components capable of terminal sterilization are subjected to terminal sterilization in the last step, and the sterilization in the preparation process or the aseptic condition is realized by process control, wherein the sterilization cannot be performed by terminal sterilization;
s2, encapsulating antibacterial, anti-inflammatory and/or repair promoting drugs by using the gel carrier solution, preparing the drugs into a drug solution by using 0.9% of normal saline or water for injection, sterilizing, adding the drug solution into the gel carrier solution at 4 ℃, uniformly mixing to form a preparation, and sterilizing; the medicine comprises antibiotics, traditional Chinese medicine extracts and hormones, wherein the antibiotics are one or more of terramycin alkali, aureomycin, penicillin, tetracycline, erythromycin, fluoroquinolone medicines and sulfonamides, the traditional Chinese medicine extracts are extracts of any several traditional Chinese medicines of safflower, motherwort, catalpol, stachydrine, trichosanthes root, baicalin, berberine, honeysuckle, angelica dahurica, Chinese violet, catechu, Chinese pulsatilla root, dahurian patrinia herb and sargentgloryvine stem, the hormones are one or more of prostaglandin, dexamethasone and cephalosporium, and the ingredients can effectively promote uterine contraction while inhibiting bacteria, are beneficial to discharge of uterine mucus and the like, and promote recovery of uterus;
s3, packaging and storing the preparation, subpackaging the preparation in a sterile centrifuge tube or a syringe, and storing at the temperature of 4 ℃.
The preparation method is simple, the prepared preparation can simplify the operation flow in application, and compared with the traditional uterine lavage method, the temperature-sensitive type drug-loaded gel preparation can effectively reduce the administration times and improve the drug retention rate, thereby obviously reducing the workload of farm culture personnel; the medicine slow release function greatly improves the local retention time and retention rate of the medicine, can better inhibit the propagation of pathogenic bacteria and improve the treatment effect; the effective components such as collagen, hyaluronic acid, chitosan, traditional Chinese medicines and hormone components can promote the repair of damaged endometrium and the like, promote the contraction of uterus, provide good intrauterine environment for the fertilization and pregnancy of dairy cows and improve the pregnancy rate of the dairy cows; the treatment times can be obviously reduced, the problems of secondary and repeated infection caused by improper operation and the like in the repeated administration process can be avoided, and the risk of cross infection is reduced; avoid the drug resistance problem: the drug resistance problem caused by repeated administration can be effectively avoided by reducing the administration times, and the treatment efficiency and the selection of a treatment method are improved; the temperature-sensitive type can obviously reduce the dosage and the frequency of each administration, and greatly saves the treatment cost, the subsequent mating cost and the like.
In practical applications, as shown in figures 2 and 3,
(1) treatment of cow endometritis: the uterus of the cow is thoroughly cleaned by using normal saline until the flushing fluid is transparent, and then the cleaning fluid is completely discharged in a rectum finger pressing mode. Then 20-30ml of temperature-sensitive injectable drug-loaded gel placed at 4 ℃ is injected into the moderate and severe endometritis milk cow through an uterine perfusion apparatus, the endometritis of the milk cow is remarkably relieved after about 7 days after the uterus is perfused with the temperature-sensitive gel, the breeding condition can be achieved after about 14 days, the effective rate is up to more than 86%, the treatment effect is remarkably higher than that of the traditional treatment mode, the treatment period and time are also remarkably shortened, and the treatment effect of the temperature-sensitive slow-release drug-loaded gel on the endometritis is proved.
(2) Prevention of endometritis of postpartum dairy cow: for postpartum cows, after the afterbirth is stripped off and the uterus is basically contracted to the normal size through rectal examination, 20-30ml of temperature-sensitive injectable drug-loaded gel is filled through a uterine perfusion apparatus, and the temperature-sensitive injectable drug-loaded gel is used as a control group without intervention.
It will be understood that modifications and variations can be made by persons skilled in the art in light of the above teachings and all such modifications and variations are intended to be included within the scope of the invention as defined in the appended claims.
Claims (9)
1. A temperature-sensitive slow-release medicine-carrying gel preparation for preventing and treating cow endometritis is characterized by comprising a temperature-sensitive gel carrier which is used for carrying medicine and is solidified into gel at a physiological temperature of being in a liquid state at 0-10 ℃, the gel carrier is coated with antibacterial and anti-inflammatory and/or repair promoting medicines, and the gel carrier is a solution mainly prepared by mixing chitosan, hyaluronic acid, collagen, methylcellulose and poloxamer.
2. The temperature-sensitive type slow-release medicine-carrying gel preparation for preventing and treating the endometritis of the milk cow according to claim 1, which is characterized in that the medicine comprises antibiotics, traditional Chinese medicine extracts and hormones.
3. The temperature-sensitive type slow-release drug-loaded gel preparation for preventing and treating cow endometritis as claimed in claim 2, wherein the antibiotic is one or more of oxytetracycline, chlortetracycline, penicillin, tetracycline, erythromycin, fluoroquinolones and sulfonamides, the Chinese medicinal extract is extract of any of safflower, motherwort, catalpol, stachydrine, trichosanthes root, baicalin, berberine, honeysuckle, angelica dahurica, Chinese violet, catechu, pulsatilla, patrinia and sargentgloryvine stem, and the hormone is one or more of prostaglandin, dexamethasone and cephalosporins.
4. The temperature-sensitive slow-release drug-loaded gel preparation for preventing and treating the endometritis of the milk cow according to claim 1, which is characterized in that the weight percentages of the chitosan, the hyaluronic acid, the collagen, the methylcellulose and the poloxamer in the solution are 1.5-2.2%, 0.05-5%, 0.5-3%, 1.5-2.2% and 5-20% in sequence.
5. A preparation method of the temperature-sensitive type slow-release drug-loaded gel preparation for preventing and treating the endometritis of the milk cow is characterized by comprising the following steps,
s1, preparing a gel carrier solution, namely mixing chitosan, hyaluronic acid, collagen, methylcellulose and poloxamer in proportion at the temperature of 0-10 ℃ to prepare the gel carrier solution, and sterilizing and disinfecting the gel carrier solution;
s2, encapsulating antibacterial, anti-inflammatory and/or repair promoting drugs in the gel carrier solution, preparing the drugs into a drug solution by using 0.9% of normal saline or water for injection, sterilizing, adding the drug solution into the gel carrier solution at 0-10 ℃, uniformly mixing to form a preparation, and sterilizing;
s3, packaging and storing the preparation, subpackaging the preparation in a sterile centrifuge tube or an injector, and storing at the temperature of 0-10 ℃.
6. The preparation method of the temperature-sensitive type slow-release drug-loaded gel preparation for preventing and treating the endometritis of the milk cow according to claim 5, characterized in that the drug comprises antibiotics, traditional Chinese medicine extracts and hormones.
7. The preparation method of the temperature-sensitive slow-release drug-loaded gel preparation for preventing and treating cow endometritis according to claim 6, wherein the antibiotic is one or more of oxytetracycline, chlortetracycline, penicillin, tetracycline, erythromycin, fluoroquinolone drugs and sulfonamide drugs, the Chinese medicinal extract is extracts of any of safflower, motherwort herb, catalpol, stachydrine, trichosanthes root, baicalin, berberine, honeysuckle flower, angelica dahurica, herba violae, catechu, pulsatilla chinensis, patrinia scabiosaefolia and sargentgloryvine stem, and the hormone is one or more of prostaglandin, dexamethasone and cephalosporins.
8. The preparation method of the temperature-sensitive slow-release drug-loaded gel preparation for preventing and treating the endometritis of the milk cow according to claim 5, characterized in that the weight percentages of the chitosan, the hyaluronic acid, the collagen, the methylcellulose and the poloxamer in the gel carrier solution are 1.5-2.2%, 0.05-5%, 0.5-3%, 1.5-2.2% and 5-20% in sequence.
9. The preparation method of the temperature-sensitive type slow-release drug-loaded gel preparation for preventing and treating the endometritis of the milk cow according to claim 5 is characterized in that the preparation of the gel carrier solution, the liquid medicine, the preparation and the package and the storage of the preparation are all carried out at the temperature of 4 ℃.
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