CN117462527A - Application of gabexate mesylate in preparation of medicines for treating pancreatitis of pets - Google Patents
Application of gabexate mesylate in preparation of medicines for treating pancreatitis of pets Download PDFInfo
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- CN117462527A CN117462527A CN202211712037.8A CN202211712037A CN117462527A CN 117462527 A CN117462527 A CN 117462527A CN 202211712037 A CN202211712037 A CN 202211712037A CN 117462527 A CN117462527 A CN 117462527A
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- oil
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- gabexate mesylate
- pancreatitis
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Classifications
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- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
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Abstract
The invention provides an application of gabexate mesylate in preparing a pharmaceutical preparation for treating pancreatitis of pets, and belongs to the field of application of chemical drugs for animals. The pharmaceutical preparation comprises gabexate mesylate serving as an active ingredient and one or more than one pharmaceutical auxiliary material, can effectively treat pancreatitis and pancreatitis complications of pets caused by factors such as parasites or virus infection, and has the advantages of outstanding prevention and treatment effects and good bioavailability.
Description
Technical Field
The invention belongs to the technical field of veterinary chemical drug application, and particularly relates to application of gabexate mesylate in preparation of drugs for treating pancreatitis of pets.
Background
Pancreatitis is an inflammatory reaction that stimulates pancreatic tissues to secrete pancreatic digestive enzymes to digest the pancreas itself under the action of certain pathogenic factors, so that the pancreatic tissues exhibit edema, hemorrhage and necrosis as main pathological changes. Inflammation of pancreatitis is inflammatory cell infiltration, typically a sterile inflammatory process.
Canine pancreatitis is an inflammatory reaction that is activated in the pancreas by various digestive enzymes secreted by exocrine pancreatic tissue, causing self-digestion and hydrolysis of the pancreas, causing damage to pancreatic tissue [ Yang Shoushen, lin Aihua, tang Runbin, etc. ] canine pancreatitis clinical characterization survey and treatment [ J ]. Black longjiang animal doctor, 2021 (2): 87-91, 97.]. Clinically, acute Pancreatitis (AP) is a common occurrence, and causes hyperlipidemia and infectious diseases (such as canine parvovirus, coronavirus and parasitic infection) caused by overeating and hormone abuse are mainly caused [ chikungunya, huang Xujun. Diagnosis and treatment of pancreatitis secondary to canine parvovirus disease [ J ]. Journal of chinese veterinarian, 2014, 50 (5): 72-74.].
Most of the diseases of the cat pancreatitis are caused by the special physiological structure of the cat pancreas, and fatty liver and biliary tract diseases (such as cholangitis, biliary tract obstruction and inflammatory bowel disease) are often accompanied with the occurrence of pancreatitis; pancreatitis is also often caused by blockage of pancreatic ducts (e.g., tumors), inflammatory bowel disease. Ischemia, hypercalcemia, and hypertriglyceridemia of the body due to hypotension or anesthesia are also one of the causes of pancreatitis. Many drugs and toxins are also believed to be associated with feline pancreatitis, such as organophosphates, esters, calcium, and the like. Other risk factors associated with feline pancreatitis include blunt trauma (e.g., car accident, high building syndrome), surgical trauma, parasitic infection (e.g., toxoplasmosis, trematodes), and infectious pathogen infection (e.g., feline calicivirus, feline infectious peritonitis virus, feline plague, and feline herpes virus), among others.
The clinical symptoms of the canine and feline pancreatitis are not specific, the clinical diagnosis is difficult, and misdiagnosis and missed diagnosis are easy to occur. At present, the general principles of treatment of the canine and feline pancreatitis are to correct water-salt balance, inhibit secretion of gastric acid and other glands, relieve pain, stop vomiting, prevent shock, prevent infection and the like. The incidence of canine cat pancreatitis has shown an increasing trend in recent years, however, there is a substantial difference between the causative cause of canine cat pancreatitis and the causative cause of human pancreatitis; and the physiological functions, the metabolic characteristics and the like of the human body and the dogs and cats are essentially different, the mutual technical difficulty of the human body medication and the dogs and cats medication exists, and no related report on the special gabexate mesylate product for dogs and cats exists at present.
Gabexate mesylate (Gabexate mesilate) is a serine protease inhibitor, and has a chemical name of p- (6-guanidine acetoxy) ethyl benzoate mesylate and a molecular formula of C 16 H 23 N 3 O 4 ·CH 4 O 3 S or C 17 H 27 N 3 O 7 S, molecular weight 417.48CAS number: 56974-61-9, and has the following structural formula.
Gabexate mesylate has the structural formula:
the research at home and abroad proves that the gabexate mesylate can inhibit the activities of protease such as trypsin, kallikrein, plasmin, thrombin and the like, thereby preventing the pathophysiological changes caused by the protease. In animal experimental acute pancreatitis, activated trypsin can be inhibited, pancreatic injury is relieved, and simultaneously, the activity of serum starch alcohol, lipase and urea nitrogen are obviously improved, and gabexate mesylate is used for preparing medicaments for treating acute light (oedema) pancreatitis and assisting in treating acute hemorrhagic necrosis type pancreatitis, but the gabexate mesylate products prepared by the methods are all taken by people, and due to the fact that physiological functions, metabolic characteristics and the like of people and dogs and cats are essentially different, no related report and research on the gabexate mesylate products special for dogs and cats exist at present.
Disclosure of Invention
Based on the problems existing in the practice, the invention provides application of gabexate mesylate in preparing a pharmaceutical preparation for treating pancreatitis of pets and complications of pancreatitis of pets.
In a first aspect, the invention provides the use of gabexate mesylate in the manufacture of a pharmaceutical formulation for the treatment of pancreatitis in pets.
The pharmaceutical preparation comprises gabexate mesylate serving as an active ingredient and one or more than one medicinal auxiliary material.
The pet is a dog or cat.
The pancreatitis of the pet is caused by one or more of pancreatic susceptibility, parasitic infectious diseases, veterinary clinical medicine factors, virus infectious diseases and the like caused by special dietary structures or pancreas physiological structures of the pet.
Preferably, the pancreatitis in pets is caused by a parasitic infectious disease, a viral infectious disease.
Preferably, the parasitic infectious diseases include parasitic infections of babesia, toxoplasma, trematodes and the like.
Preferably, the viral infectious diseases include parvoviral infectious diseases, coronavirus infectious diseases, feline infectious peritonitis, and the like.
Preferably, the veterinary clinical drug factor includes hormone abuse, anesthesia complications, and the like.
In a second aspect, the invention provides the use of gabexate mesylate in the manufacture of a pharmaceutical formulation for the treatment of complications of pancreatitis in pets.
The complications of the pancreatitis of the pets are one or more of cholangitis, biliary tract obstruction, inflammatory bowel disease, metabolic alkalosis and catarrhal inflammation.
The gabexate mesylate pharmaceutical preparation for treating pancreatitis and pancreatitis complications of pets can be administered by intravenous, local perfusion in biliary tract, intramuscular or subcutaneous and oral routes, preferably intravenous administration.
Preferably, the pharmaceutical preparation for treating pancreatitis and pancreatitis complications of pets is gabexate mesylate freeze-dried powder injection or gabexate mesylate injection.
More preferably, the pharmaceutical preparation is gabexate mesylate fat emulsion injection.
The administration dosage of the gabexate mesylate fat emulsion injection is 2-6 mg/kg.
In a third aspect, the invention provides a gabexate mesylate fat emulsion injection which consists of gabexate mesylate, oil for injection, lecithin, glycerol and water for injection.
The fat emulsion injection comprises the following components in percentage by mass and volume: 1.0 to 3.0 percent of gabexate mesylate, 8 to 30 percent of oil for injection, 0.5 to 2.0 percent of lecithin and 3 to 10 percent of glycerol, and the water for injection is supplemented to 100 percent.
Preferably, the fat emulsion injection comprises the following components in percentage by mass and volume: 1.5 to 2.5 percent of gabexate mesylate, 8.0 to 15.0 percent of oil for injection, 1.0 to 2.0 percent of lecithin, 3.0 to 5.0 percent of glycerol and 100 percent of water for injection.
More preferably, the fat emulsion injection comprises the following components in percentage by mass and volume: gabexate mesylate 2.0%, oil for injection 15%, lecithin 2%, glycerol 4%, and water for injection 100%.
The oil for injection is one or more selected from soybean oil, olive oil, safflower oil, sesame oil, coconut oil, castor oil, fish oil, medium chain monoglyceride, medium chain diglyceride and medium chain triglyceride.
Preferably, the oil for injection is one or more selected from fish oil, medium chain triglyceride, soybean oil and castor oil.
More preferably, the oil for injection is selected from one or two of fish oil and medium chain triglycerides.
Preferably, the lecithin is egg yolk lecithin.
The invention provides a preparation method of gabexate mesylate fat emulsion injection, which comprises the following steps:
(1) Preparing an oil phase: weighing the gabexate mesylate and the oil for injection according to the prescription, adding lecithin, heating to 70-90 ℃, and stirring and dissolving to obtain an oil phase;
(2) Preparing an aqueous phase: weighing the glycerol and the water for injection according to the prescription, heating to 70-90 ℃, stirring and dissolving to obtain a water phase;
(3) Under the heat preservation condition of 70-90 ℃, adding the oil phase into the water phase while shearing at 7000rpm, and shearing for 20min after the addition is finished, thus forming the colostrum. The colostrum is passed through a high-pressure homogenizer for 2 times, and the pressure is 800-1200 bar, so as to obtain emulsion. Packaging into penicillin bottles, filling nitrogen, sealing, and rotary sterilizing to obtain the final product.
The beneficial effects are that:
1. the invention provides application of gabexate mesylate in preparing a pharmaceutical preparation for preventing and treating pancreatitis and pancreatitis complications of pets, in particular dogs and cats, wherein the dosage of the gabexate mesylate in treating pancreatitis and pancreatitis complications of cats is specifically 2-6 mg/kg, and when the gabexate mesylate is administrated to a pet intravenous drip for suffering from pancreatitis, the clinical effect is obvious, and the gabexate mesylate is a medicament with better treatment and prevention effects, which is suitable for the pancreatitis of dogs and cats and the complications thereof.
2. The fat emulsion injection containing the gabexate mesylate is used in the treatment process of canine and feline pancreatitis caused by specific causes, can inhibit the activities of protease such as trypsin, kallikrein, plasmin, thrombin and the like so as to reduce pancreas injury, and can obviously improve the activities of serum amylase and lipase and abnormal rise of urea nitrogen.
3. The fat emulsion is mixed fat emulsion, has better organism metabolism and tolerance, and has a certain function of regulating organism immunity. The injection oil in the formula is a mixture of fish oil and medium chain triglycerides, wherein the fish oil is rich in omega-3 polyunsaturated fatty acids, and has more excellent effects of reducing inflammatory reaction and regulating immunity. Compared with the traditional vegetable oil, the medium chain triglyceride has better antioxidation stability and drug solubility, is not easy to cause the increase of blood fat, and reduces the incidence rate of adverse reaction.
Detailed description of the preferred embodiments
The foregoing will be described in further detail by way of the following detailed description of the embodiments. It should not be construed that the scope of the above subject matter is limited to the following examples. All techniques implemented based on this disclosure are within the scope.
Example 1
The preparation method of the gabexate mesylate fat emulsion injection comprises the following steps:
preparing an oil phase: adding gabexate mesylate and fish oil into egg yolk lecithin according to a group Fang Liangqu, heating to 90 ℃, and stirring and dispersing to obtain the additive; preparing an aqueous phase: adding glycerol into appropriate amount of injectable water, stirring for dissolving, and heating to 90deg.C; mixing the oil phase and the water phase, stirring, adding injectable water to a preparation amount, shearing at 7000rpm for 30min to form colostrum, adding gabexate sulfonate with final concentration of 2.1% (w/v), homogenizing at 1000bar pressure for 2 times to obtain emulsion, packaging into penicillin bottles, sealing, and sterilizing to obtain fat emulsion.
The formula list is as follows:
formulation prescription | Proportion of |
Gabexate mesylate | 2.0%w/v |
Fish oil | 12.0%w/v |
Egg yolk lecithin | 1.5%w/v |
Glycerol | 5.0%w/v |
Water for injection | To 100% |
Example 2
Heating water for injection to 80deg.C, adding glycerol, and dissolving to obtain water phase; heating fish oil and medium chain triglyceride to 80deg.C, adding egg yolk lecithin and gabexate mesylate, and stirring to dissolve to obtain oil phase; adding the oil phase into the water phase, adding water for injection, controlling the temperature in water bath to 80 ℃, shearing at 7000rpm at high speed, and dispersing for 30min to form colostrum; homogenizing at 1000bar under high pressure for 2 times, filtering, bottling, and sterilizing.
The formula list is as follows:
example 3
The preparation method of the gabexate mesylate fat emulsion injection comprises the following steps:
heating water for injection to 75deg.C, adding glycerol for dissolution, and collecting water phase; heating fish oil and medium chain triglyceride to 75deg.C, adding egg yolk lecithin and gabexate mesylate, stirring to dissolve, and taking the mixture as oil phase; adding the oil phase into the water phase, adding water for injection, controlling the temperature in water bath at 75deg.C, shearing at 7000rpm at high speed for 30min, and dispersing to obtain colostrum; homogenizing at 1000bar under high pressure for 2 times, filtering, bottling, and sterilizing.
The formula list is as follows:
formulation prescription | Proportion of |
Gabexate mesylate | 2.0%w/v |
Fish oil | 5.0%w/v |
Medium chain triglycerides | 10.0%w/v |
Egg yolk lecithin | 2.0%w/v |
Glycerol | 4.0%w/v |
Water for injection | To 100% |
Example 4
The preparation method of the gabexate mesylate fat emulsion injection comprises the following steps:
heating water for injection to 70deg.C, and adding glycerol to dissolve to obtain water phase; heating medium chain triglyceride to 70deg.C, adding egg yolk lecithin and gabexate mesylate, and stirring to dissolve to obtain oil phase; adding the oil phase into the water phase, adding injection water, controlling the temperature in water bath to 70 ℃, shearing at 7000rpm at high speed, and dispersing for 30min to form colostrum; homogenizing at 1000bar under high pressure for 2 times, filtering, bottling, and sterilizing.
The formula list is as follows:
example 5
The preparation method of the gabexate mesylate fat emulsion injection comprises the following steps:
heating water for injection to 60deg.C, and adding glycerol to dissolve to obtain water phase; heating oleum Olivarum to 60deg.C, adding egg yolk lecithin and gabexate mesylate, and stirring to dissolve to obtain oil phase; adding the oil phase into the water phase, adding injection water, controlling the temperature in water bath at 60 ℃, shearing at 7000rpm at high speed, and dispersing for 30min to form colostrum; homogenizing at 1000bar under high pressure for 2 times, filtering, bottling, and sterilizing.
The formula list is as follows:
formulation prescription | Proportion of |
Gabexate mesylate | 2.0%w/v |
Olive oil | 10.0%w/v |
Egg yolk lecithin | 1.5%w/v |
Glycerol | 4.5%w/v |
Water for injection | To 100% |
Example 6 test for detecting Properties of fat emulsion injection
Key indexes of gabexate mesylate fat emulsion injection obtained in examples 1 to 5 were detected, and the results are shown in the following table:
the gabexate mesylate fat emulsion injection prepared in the present examples 1 to 4 was subjected to particle size, zeta potential and pH detection, and the detection results were: the average grain diameter is 184-218 nm,90% of particles are less than or equal to 273nm, the Zeta potential is-53-61 mV, and the pH value is 6.5-7.0. The water phase temperature is controlled at 70-90 ℃, the oil phase temperature is controlled at 70-90 ℃, the primary emulsion temperature is controlled at 70-90 ℃, and the homogenization temperature is 35-50 ℃, so that the particle size and the distribution of the prepared samples have no obvious difference in Zeta potential. On the premise of the temperature control range of the invention, the change of temperature has no obvious influence on the Zeta potential, the average particle size and the distribution of the emulsion, and the product quality is stable.
Particle size, zeta potential and pH value of the gabexate mesylate fat emulsion injection prepared in example 5 are detected, and the detection result is as follows: the average grain diameter is 275-293 nm,90% of the grains are less than or equal to 393nm, the pH value is 6.0-6.9, and the Zeta potential is-27-32 mV. As can be seen from the comparison of the data in examples 5 and examples 1 to 4, the oil for injection, the water phase temperature, the oil phase temperature, the homogenization temperature of the colostrum and the microfluidics are different from those in examples 1 to 4, the average particle size of the product is larger, the distribution of emulsion particles is wider, and the stability is slightly poor.
Example 7 treatment of pancreatitis caused by babesia in pet dogs
On day 8 and 15 of 2022, the hospital received 1 female tady dogs, 5 months of age 2, and 2.95kg of body weight. The sick dogs were immunized according to immunization program, near 3d mental retardation, diarrhea, a small amount of blood filaments in the feces, vomiting 1 time a day, high abdominal tension, and no contact. The skin on the body surface is marked with biting marks, and the owner is informed of travel from dogs to villages by 2 months.
Clinical examination: it is found that the sick dogs have mental depression, visual mucosa yellow staining, nasal mirror dryness and body temperature of 39.7 ℃. Palpation of the abdomen is painful, the anus is contaminated by faeces, and the anus is slightly dehydrated. Laboratory examination: CCV detection and babesia examination were performed based on clinical symptoms combined with immunization. The canine coronavirus detection was performed first, showing negative. Blood was collected for smear microscopy and blood examination, stained with Diff's quick stain, and examined under a 100-fold microscope to visualize punctiform Babesia gibsonii.
Babesia canis disease is generally transmitted by ectoparasite ticks, primarily affecting erythrocytes, causing hemolysis and anemia, which can induce pancreatitis.
The doctor holds the affected dogs on the back, shaves the abdominal hair and performs color ultrasound examination. The results showed that the pancreas region was hypoechoic and the bile duct was dilated. Color Doppler ultrasound indicates that the pancreas is damaged. The test is carried out by adopting Edison cPL rapid detection test paper, and the result is positive, so that the dog is prompted to suffer from pancreatitis.
The treatment principle is as follows: controlling primary disease, replenishing blood, correcting acid-base and electrolyte balance, improving resistance, relieving pain, stopping vomiting, inhibiting enzyme activity, and preventing secondary infection. The prescription is as follows: intravenous injection: (1) 30ml of 0.9% sodium chloride solution + 150mg of ampicillin; (2) 50ml of 0.9% sodium chloride solution+gabexate mesylate 12mg (example 1); (3) 0.5mLVc,0.3mLATP,0.3mLCOA,0.3mLVB were added to a 5% glucose solution; subcutaneous injection: (4) 11mg of triazamidine; (5) blood-rich gram 0.5ml; (6) 0.3ml of anti-emetic agent.
After the treatment by the method, the Edison cPL rapid test paper is detected again after 4 days, and the test result is negative, which indicates that the plasma specific lipase value is recovered to the normal level. After 1 week the sick dogs were gradually improved and the mental appetite recovered, and after 1 month the dogs were rechecked as negative for babesia.
Example 8 treatment of pancreatitis caused by pet canine coronavirus
1 white male was older than Xiong Quan, 1 year, 4.5kg, sterilized, normally insect repellent, incompletely immunized, 10 months of 2022, 17 days ago for clinic. Complaints: the sick dogs eat chicken and milk in noon in 10 months and 16 days, begin to vomit (3-4 times) after a while, relieve the bowels for 2 times, and the feces are hard and thin after each other; the following day no food was taken.
Clinical examination: the body temperature of the affected dogs is 39 ℃, visual mucous membrane is pale, eyeballs are depressed, nasal lenses are dry, spirit is depressed, and the dogs are reluctant to move; vomit is undigested food and yellow mucus; the feces are water-like and green.
Laboratory examination: a small amount of feces of a dog is taken, and the results are tested by using a Canine Coronavirus (CCV), canine Parvovirus (CPV) and Canine Distemper Virus (CDV) antigen rapid test card, so that CCV (+), CPV (original) and CDV (original) are shown. The anterior extremity vein of the affected dog is used for blood biochemistry and canine pancreatitis rapid detection test paper (cPL) examination. Albumin content decreases, suggesting bowel disease; the amylase activity was greatly increased, suggesting acute pancreatitis. The test is carried out by adopting Edison cPL rapid detection test paper, and the result is positive, so that the dog is prompted to suffer from pancreatitis.
The established treatment principles are antiviral, anti-inflammatory and symptomatic treatment and the like (intravenous injection, continuous administration for 7 d) aiming at the actual situation of the suffering dogs: (1) 20mL of 0.9% sodium chloride solution plus 0.45g of ampicillin sodium plus 1.0mL of ribavirin; (2) 25mL of metronidazole sodium chloride; (3) 20mL of 0.9% sodium chloride solution+inosine 1.0mL; (4) 40mL of 5% glucose solution and 1 branch of water-soluble vitamin; (5) 30mL of 5% glucose solution+ATP2.0mL; (6) 30mL of 5% glucose solution+18 mg of gabexate mesylate (example 3); (7) 40mL of 5% glucose solution+5.0 mL of life element; (8) 40mL of 5% glucose solution+2.5 mL of Sai Te long; (9) 0.45mL of anti-emetic; canine IFN-alpha 200 ten thousand IU. After 1 week of treatment, the activities of serum amylase and lipase are recovered to be normal, the vomiting of the suffering dogs is stopped, the feces are formed, the spirit is good, and the appetite is improved. The owner brings home, and the doctor orders to pay attention to diet, so that stress is reduced. After 2 weeks, the dogs were informed by telephone return visit, had a lively mind, had good appetite, had normal urination and recovery.
In the case, canine pancreatitis is probably caused by canine coronavirus diseases, various digestive enzymes secreted by exocrine pancreatic tissues are activated in pancreas, so that pancreas self-digestion and hydrolysis are caused, pancreatic tissues are damaged, and the canine pancreatitis is treated by gabexate mesylate, and inosine, ATP, vital elements and other medicaments are used for supplementing energy for organisms, and meanwhile, the canine pancreatitis is fasted, water-forbidden, antibacterial and anti-inflammatory. After 1 week of treatment, the vomiting of the suffering dogs is stopped, the feces are formed, the spirit is good, the appetite is improved, and the diagnosis and treatment are reasonable.
Canine coronavirus diarrhea is a serious hazard to puppies, but death is rare with the age of dogs and the sudden advance of modern medical level. However, if a plurality of viruses are mixed and infected, the healing difficulty is greatly improved, and the situation of internal diseases such as parasitic diseases, pancreatitis and the like is more common.
EXAMPLE 9 treatment of pancreatitis caused by trisomy in pet cats
Short cat, 2 years old, male (castrated), 2.8kg body weight, complete history of vaccine. The pet owner complains about the foam floor mat by mistake 1 month before suffering from the cat, and then continuously takes the vomiting symptom, and the pet owner drenches probiotics at home, and does not see symptom relief until 4 days before seeing a doctor, and the appetite is abolished.
Clinical examination: suffering from mental depression, vomiting and anorexia, three-stage dehydration, no diarrhea, abdominal pain before palpation, visual pale yellow and stained mucous membrane, capillary refill time of 4s, body temperature of 37.6 ℃, breathing 40 times/min, and heart rate 190 times/min.
Color Doppler ultrasonic examination of the affected cat shows that the diameter of the large papilla of the duodenum is about 5mm (the normal diameter is less than 2.4 mm) from B ultrasonic scanning, which indicates that inflammation exists in pancreatic duct and bile duct; double signs of gallbladder, indicating cholecystitis; the duodenal mucosa layer is seen with a hyperechogenic bright line, indicating duodenal fibrosis. And (3) testing by adopting Edison cPL rapid test paper, wherein the result is positive. Indicating that the content of the plasma specific lipase exceeds the standard, the pancreatitis can be pointed.
The rehydration liquid maintains vascular perfusion, prevents shock, controls vomiting and secondary infection, relieves pain and treats the trisomy. Intravenous injection: sodium lactate ringer 50ml + compound butafos injection 1ml,5% glucose 50ml + gabexate mesylate 10mg (example 2), 5% glucose + vitamin B complex 1ml; subcutaneous injection: 0.5ml of anti-emetic agent. 40mg of amoxicillin and clavulanate potassium, 45mg of enrofloxacin and 1.5mg of butorphanol.
The test result is negative after rechecking the Edison cPL rapid test paper on the fifth day. Indicating that the plasma specific lipase content returns to normal. Through 10 days of hospitalization, vital signs are stable, mental conditions are improved, and appetite is restored. The prognosis of trisomy is greatly different, and pancreatitis needs to be consolidated and treated for a long time.
Catarrhal trisomy is a three disease association, possibly associated with an ascending infection of gastrointestinal bacteria. Because of the unique anatomy of cats, the pancreas is more susceptible to upstream infections by the pancreas in combination with bile ducts at the papilla prior to entry into the duodenum. It has been found that cats with cholangitis have a higher prevalence of pancreatitis and intestinal inflammation. Pancreatitis is associated with 60% of cats with cholangitis, and with 50% of cats with cholecystitis.
The foregoing description of the embodiments has been provided for the purpose of illustrating the general principles of the invention, and is not meant to limit the scope of the invention, but to limit the invention to the particular embodiments, and any modifications, equivalents, improvements, etc. that fall within the spirit and principles of the invention are intended to be included within the scope of the invention.
Claims (10)
1. The application of gabexate mesylate in preparing a pharmaceutical preparation for treating pancreatitis of pets is characterized in that the pharmaceutical preparation comprises the active ingredient gabexate mesylate and one or more than one pharmaceutical auxiliary materials.
2. The use according to claim 1, wherein said pancreatitis in pets is caused by one or more of a pancreatic susceptibility, a parasitic infectious disease, a veterinary clinical drug factor, a viral infectious disease, caused by a specific dietary structure or a pancreatic physiological structure of pets.
3. The application of gabexate mesylate in preparing a pharmaceutical preparation for treating complications of pancreatitis in pets is characterized in that the complications of pancreatitis in pets are one or more of cholangitis, biliary tract obstruction, inflammatory bowel disease, metabolic alkalosis and catarrhal trisomy.
4. Use according to claim 1 or 3, characterized in that the pharmaceutical preparation is gabexate mesylate fat emulsion injection.
5. The gabexate mesylate fat emulsion injection is characterized by comprising the following components in percentage by mass and volume: 1.0 to 3.0 percent of gabexate mesylate, 8 to 30 percent of oil for injection, 0.5 to 2.0 percent of lecithin and 3 to 10 percent of glycerol, and the water for injection is supplemented to 100 percent.
6. The gabexate mesylate fat emulsion injection according to claim 5, wherein the fat emulsion injection comprises the following components in percentage by mass and volume: 1.5 to 2.5 percent of gabexate mesylate, 8.0 to 15.0 percent of oil for injection, 1.0 to 2.0 percent of lecithin, 3.0 to 5.0 percent of glycerol and 100 percent of water for injection.
7. The gabexate mesylate fat emulsion injection according to claim 5 or 6, wherein the oil for injection is selected from one or more of soybean oil, olive oil, safflower oil, sesame oil, coconut oil, castor oil, fish oil, medium chain monoglyceride, medium chain diglyceride, medium chain triglyceride.
8. The gabexate mesylate fat emulsion injection according to claim 7, wherein the oil for injection is one or more selected from the group consisting of fish oil, medium chain triglycerides, soybean oil, castor oil.
9. A method for preparing the gabexate mesylate fat emulsion injection according to any one of claims 5 to 8, comprising the following steps:
(1) Preparing an oil phase: weighing the gabexate mesylate and the oil for injection according to the prescription, adding lecithin, heating to 70-90 ℃, and stirring and dissolving to obtain an oil phase;
(2) Preparing an aqueous phase: weighing the glycerol and the water for injection according to the prescription, heating to 70-90 ℃, stirring and dissolving to obtain a water phase;
(3) Adding the oil phase into the water phase while shearing at 7000rpm at high speed under the heat preservation condition of 70-90 ℃, and shearing for 20min after the addition is finished to form colostrum; the colostrum is processed by a high-pressure homogenizer for 2 times under the pressure of 800-1200 bar to obtain emulsion; packaging into penicillin bottles, filling nitrogen, sealing and sterilizing to obtain the final product.
10. The use according to claim 4, wherein the administration dose of the gabexate mesylate fat emulsion injection is 2 to 6mg/kg.
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