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 PDF

Info

Publication number
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
Authority
CN
China
Prior art keywords
preparation
temperature
gel
endometritis
preventing
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202210053250.6A
Other languages
Chinese (zh)
Inventor
王琳
邹杰
严炎刘星
李鉴墨
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kangxi Biomedical Shenzhen Co ltd
Original Assignee
Kangxi Biomedical Shenzhen Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kangxi Biomedical Shenzhen Co ltd filed Critical Kangxi Biomedical Shenzhen Co ltd
Priority to CN202210053250.6A priority Critical patent/CN114404356A/en
Publication of CN114404356A publication Critical patent/CN114404356A/en
Pending legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/429—Thiazoles condensed with heterocyclic ring systems
    • A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
    • A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/65—Tetracyclines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/63—Arthropods
    • A61K35/64—Insects, e.g. bees, wasps or fleas
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/232—Angelica
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/286—Carthamus (distaff thistle)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/35—Caprifoliaceae (Honeysuckle family)
    • A61K36/355—Lonicera (honeysuckle)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/42—Cucurbitaceae (Cucumber family)
    • A61K36/428—Trichosanthes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/486—Millettia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/533—Leonurus (motherwort)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/84—Valerianaceae (Valerian family), e.g. valerian
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/86—Violaceae (Violet family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

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

Temperature-sensitive type slow-release drug-loaded gel preparation for preventing and treating cow endometritis and preparation method thereof
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 ℃.
CN202210053250.6A 2022-01-18 2022-01-18 Temperature-sensitive type slow-release drug-loaded gel preparation for preventing and treating cow endometritis and preparation method thereof Pending CN114404356A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202210053250.6A CN114404356A (en) 2022-01-18 2022-01-18 Temperature-sensitive type slow-release drug-loaded gel preparation for preventing and treating cow endometritis and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202210053250.6A CN114404356A (en) 2022-01-18 2022-01-18 Temperature-sensitive type slow-release drug-loaded gel preparation for preventing and treating cow endometritis and preparation method thereof

Publications (1)

Publication Number Publication Date
CN114404356A true CN114404356A (en) 2022-04-29

Family

ID=81274180

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202210053250.6A Pending CN114404356A (en) 2022-01-18 2022-01-18 Temperature-sensitive type slow-release drug-loaded gel preparation for preventing and treating cow endometritis and preparation method thereof

Country Status (1)

Country Link
CN (1) CN114404356A (en)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1730097A (en) * 2005-07-25 2006-02-08 华中农业大学 Pharmaceutical composition for preventing and curing endometritis and retained afterbirth disease of milk cow
CN101310734A (en) * 2007-05-22 2008-11-26 史义林 Chinese and western combine compound uterus perfusate for treating cow endometritis
US20120052093A1 (en) * 2009-04-23 2012-03-01 Cornell University Compositions and methods for preventing and treating uterine disease
CN109568262A (en) * 2019-01-04 2019-04-05 华南农业大学 A kind of Doxycycline Temperature-sensitive in situ gel uterus perfusion and preparation method thereof for sow
CN113842358A (en) * 2021-10-29 2021-12-28 佛山市南海东方澳龙制药有限公司 Novel veterinary uterus injectant and preparation method and application thereof
US20220008439A1 (en) * 2018-07-30 2022-01-13 Virbac Novel use of glucocorticoids for the treatment of epithelial microbial infections of a fluid containing organ with a natural exterior orifice in mammals

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1730097A (en) * 2005-07-25 2006-02-08 华中农业大学 Pharmaceutical composition for preventing and curing endometritis and retained afterbirth disease of milk cow
CN101310734A (en) * 2007-05-22 2008-11-26 史义林 Chinese and western combine compound uterus perfusate for treating cow endometritis
US20120052093A1 (en) * 2009-04-23 2012-03-01 Cornell University Compositions and methods for preventing and treating uterine disease
US20220008439A1 (en) * 2018-07-30 2022-01-13 Virbac Novel use of glucocorticoids for the treatment of epithelial microbial infections of a fluid containing organ with a natural exterior orifice in mammals
CN109568262A (en) * 2019-01-04 2019-04-05 华南农业大学 A kind of Doxycycline Temperature-sensitive in situ gel uterus perfusion and preparation method thereof for sow
CN113842358A (en) * 2021-10-29 2021-12-28 佛山市南海东方澳龙制药有限公司 Novel veterinary uterus injectant and preparation method and application thereof

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
曲晓宇;张四喜;陶娌娜;宋燕青;: "盐酸布替萘芬阴道用温敏水凝胶的制备及体外释放度的考察", 中国医院药学杂志, vol. 35, no. 19, pages 1752 - 1755 *
赵汉臣等: "《工业药剂学》", 中国医药科技出版社, pages: 730 *
郝文艳;张丽花;郑增娟;李汉高;杜丽娜;: "土霉素原位凝胶的制备及抑菌效果评价", 国外医药(抗生素分册), vol. 39, no. 04, pages 348 - 352 *

Similar Documents

Publication Publication Date Title
EP3389690B1 (en) Formulations and methods for controlling the reproductive cycle and ovulation
Stevenson et al. The effect of methyl cyanoacrylate tissue adhesive on the human fallopian tube and endometrium
CN114404356A (en) Temperature-sensitive type slow-release drug-loaded gel preparation for preventing and treating cow endometritis and preparation method thereof
CN101310734A (en) Chinese and western combine compound uterus perfusate for treating cow endometritis
CN101897758A (en) Traditional Chinese medicinal composition for curing animal womb inflammation and other postpartum diseases
CN102846725B (en) Compound povidone iodine suppository and preparation method and application thereof
RU2432945C1 (en) Veterinary composition for prevention and treatment of various forms of endometritis, which contains propranol in combination with antibacterial component and veterinary medication for prevention and treatment of various forms of endometritis
Lippert et al. INDUCTION OF ABORTION BY THE EXTRA–AMNIOTIC ADMINISTRATION OF PROSTAGLANDIN GELS
CN101982198B (en) Perfusion medicinal oil for treating hysteritis of cow and preparation method thereof
CN106237029B (en) A kind of aloe antibiotic gel and preparation method thereof
CN1544004A (en) Chinese traditional medicine perfusate for preventing and treating female livestock barrenness
CN110507736B (en) A Chinese medicinal perfusate for treating endometritis of female animal, and its preparation method
CN104288162B (en) A kind of milch cow doxycycline hydrochloride uterus injectant and preparation method thereof
CN112022879A (en) Gynecological vaginal mucosa injury and wound repair sol solution and preparation method thereof
CN104784311B (en) Composition of medicine for preventing and treating animal aphtha hoof Huang and preparation method thereof
CN101972451B (en) Compound infusion preparation of Chinese herbal medicines and western medicines for treating cow hysteritis and preparation method thereof
CN101849992A (en) Medicament for treating inferior turbinate hypertrophy and method for preparing same
Pulfer et al. Treatment of postpartum metritis in dairy cows
CN105434456B (en) A kind of chitosan danshen injections and preparation method thereof
CN104825478B (en) A kind of preparation method for being used to treat the pharmaceutical composition and its perfusion liquid of cow endometritis
CN105193934B (en) Compound essential oil for treating livestock endometritis and preparation method thereof
CN103893300A (en) Traditional Chinese medicine composition for treating dairy cow endometritis, preparation method and application
CN113975263B (en) Composition for inhibiting fungi and preparation method and application thereof
CN102552295B (en) Medicine for treating internal and external hemorrhoids and preparation method thereof
Naram et al. Ayurveda Interventions in the Management of Tubal Blockages-Case Studies

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination