CN115957261A - Pharmaceutical composition for treating or preventing avian enterovirus syndrome and application thereof - Google Patents
Pharmaceutical composition for treating or preventing avian enterovirus syndrome and application thereof Download PDFInfo
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Abstract
The application discloses a pharmaceutical composition for treating or preventing avian enterovirus syndrome, which is prepared from the following raw materials in parts by weight: 50-100 parts of hairyvein agrimony, 25-75 parts of red-knees herb and 70-140 parts of oldenlandia diffusa. The composition can be used for treating or preventing enterovirus syndrome of poultry and intestinal infectious diseases of poultry caused by abnormal proliferation of bacteria, protozoa, and viruses.
Description
Technical Field
The present application relates to the field of avian medicine, in particular to a pharmaceutical composition for treating or preventing avian enterovirus syndrome and its application.
Background
Enterovirus syndrome is a comprehensive disease caused by multiple causes, such as inflammation, thickening, shedding, bleeding, necrosis and the like of intestinal mucosa, can occur all the year round, but occurs more in summer, autumn, winter and when climate and temperature difference change are large, and the disease is mostly caused by commercial poultry, hybrid chickens and commercial laying hens of 20-35 days old. The sick chicken group is mainly characterized by a series of symptoms of reduced feed intake, slow growth, severe diarrhea, organism dehydration, reduced feed reward and the like. It is not caused by a single pathogen, but is a mixed infection of intestinal tract induced by multiple factors such as infectious factors (viral diseases, bacterial diseases, protozoal diseases, etc.) and non-infectious factors (environmental changes, poor feeding management, drug abuse). The current view is that the pathogenesis of the enterovirus syndrome is that small intestinal mucosa is inflamed due to coccidian and bacteria infection, so that the intestinal wall has the manifestations of swelling, thickening, bleeding and the like, and then a large amount of mucosal epithelial cells are disintegrated, shed and necrotized, so that the secretion and absorption functions of the gland of the intestinal tract are reduced, and the defects of nutrition deficiency, feed conversion rate reduction and growth performance reduction are caused; on the other hand, because the mass propagation of pathogens such as coccidium can cause intestinal inflammation, the mucosal epithelial cells are disintegrated and fall off, and meanwhile, nutrients are consumed to cause a subcutaneous anaerobic environment, so that the infection of anaerobic bacteria such as clostridium welchii entering along with the feed is accelerated, the reproductive capacity is enhanced, and simultaneously, a large amount of exotoxin is generated to further cause the injury of the intestinal tract and aggravate the disease process. Thus, chicken enterovirus syndrome is considered to be one of the major intestinal infections causing significant economic losses in the chicken industry. Due to the diversity and complexity of etiology, currently, a comprehensive treatment scheme integrating antibacterial drugs, anticoccidial drugs and antiviral drugs is mainly adopted clinically, so that the generation of drug residues and bacterial drug resistance is increased, and public sanitation and food safety are influenced; meanwhile, due to unreasonable medication, electrolyte disorder is often caused, diseases are aggravated, and larger loss is brought to farmers.
Chinese patent application CN201610698974.0 discloses a Chinese medicinal composition for preventing and treating enterovirus syndrome of poultry: 20-30 parts of cattail pollen, 15-25 parts of turmeric, 15-25 parts of peach kernel, 10-30 parts of red paeony root, 10-30 parts of rhizoma alismatis, 10-30 parts of radix curcumae, 10-25 parts of immature bitter orange and 10-30 parts of bighead atractylodes rhizome; the Chinese invention patent application CN201811443710.6 discloses a pure traditional Chinese medicine composition for preventing and treating enterovirus syndrome of poultry: 10 to 20 portions of Chinese pulsatilla root, 10 to 20 portions of common andrographis herb, 10 to 20 portions of patchouli, 10 to 20 portions of lightyellow sophora root, 10 to 15 portions of amur corktree bark, 10 to 15 portions of golden thread and 10 to 20 portions of talc. Both of these patent applications strengthen the intestinal mucosa barrier function and improve the intestinal micro-ecological internal environment to inhibit the abnormal metabolic activity of germs, fungi, protozoa and viruses, and fail to inhibit and kill pathogenic microorganisms to treat the poultry enterovirus syndrome.
The Chinese invention patent application CN201110330965.3 discloses a traditional Chinese medicine powder capable of effectively preventing and treating laying hen enterovirus syndrome: 2-5 parts of radix sophorae flavescentis, 2-5 parts of hawthorn, 2-5 parts of white peony root, 1-2 parts of coptis chinensis, 1-2 parts of elecampane and 1-2 parts of rheum officinale. Chinese invention patent application CN201310728696.5 discloses a traditional Chinese medicine composition for preventing and treating enterovirus syndrome of poultry: 10-30% of dimetridazole, 4-10% of neomycin sulfate, 2-8% of quindox ester, 10-30% of lysozyme, 0.5-5% of etamsylate, 3-10% of TMP (Trimethoprim lactate), and the balance of pharmaceutically applicable auxiliary materials, and the composition integrates multiple drugs such as an antiprotozoal drug, an antibacterial drug, an anticoccidial drug, a hemostatic drug, a synergist and the like, so that multiple effects such as antibiosis, disinsection, hemostasis and the like are achieved, the composition conforms to the treatment principle of multiple pathogens of enterotoxigenic syndromes, but the composition does not conform to the safe and effective medication requirements of modern animal breeding industry under the consumption environment that the demand of people on safe, nutritional and high-quality and delicious animal-derived foods is continuously increased.
Disclosure of Invention
The technical problem to be solved by one or more embodiments of the present application is to overcome the above-mentioned drawbacks of the prior art and to provide a pharmaceutical composition which is effective in preventing and treating enterotoxemia in poultry.
One or more embodiments of the present application provide a pharmaceutical composition for treating or preventing avian enterovirus syndrome, which is prepared from the following raw materials in parts by weight: 50-100 parts (such as 50, 60, 70, 80, 90 and 100 parts) of hairyvein agrimony, 25-75 parts (such as 25, 35, 45, 55, 65 and 75 parts) of red-knees herb and 70-140 parts (such as 70, 80, 90, 100, 110, 120, 130 and 140 parts) of oldenlandia diffusa.
In one or more embodiments, the pharmaceutical composition is extracted from the following raw materials in parts by weight: 50-100 parts (such as 50, 60, 70, 80, 90 and 100 parts) of hairyvein agrimony, 25-75 parts (such as 25, 35, 45, 55, 65 and 75 parts) of red-knees herb and 70-140 parts (such as 70, 80, 90, 100, 110, 120, 130 and 140 parts) of oldenlandia diffusa.
In one or more embodiments, the pharmaceutical composition is prepared by extracting the following raw materials in parts by weight with water: 50-100 parts (such as 50, 60, 70, 80, 90 and 100 parts) of hairyvein agrimony, 25-75 parts (such as 25, 35, 45, 55, 65 and 75 parts) of red-knees herb and 70-140 parts (such as 70, 80, 90, 100, 110, 120, 130 and 140 parts) of oldenlandia diffusa.
In one or more embodiments, the pharmaceutical composition comprises 10-20 parts by weight (e.g., 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 parts by weight) of the particles of the aqueous extract of hairyvein agrimonia herb and bud, 5-15 parts by weight (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 parts by weight) of the particles of the aqueous extract of polygonum hydropiper, 10-20 parts by weight (e.g., 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 parts by weight) of the particles of the aqueous extract of hedyotis diffusa.
In one or more embodiments, the pharmaceutical composition comprises 15 parts by weight of the granule of the water extract of hairyvein agrimonia herb and bud, 10 parts by weight of the granule of the water extract of red-knees herb and 15 parts by weight of the granule of the water extract of spreading hedyotis herb.
In one or more embodiments, the agrimonia pilosa water extract granule is prepared by the following method: extracting herba et Gemma Agrimoniae with water, concentrating the extractive solution, drying, adding polyvinylpyrrolidone as adjuvant, and granulating to obtain the herba et Gemma Agrimoniae water extract granule.
In one or more embodiments, the agrimonia pilosa water extract granule is prepared by the following method: taking a hairyvein agrimony medicinal material, adding 8-12V/W times (for example, 8, 9, 10, 11 and 12V/W times) of water, carrying out reflux extraction for 1-2 hours, extracting for 1-3 times (for example, 1, 2 and 3 times), filtering, combining filtrates, carrying out reduced pressure concentration until the relative density is 1.05-1.10 (for example, 1.05, 1.06, 1.07, 1.08, 1.09 and 1.10), carrying out spray drying at a peristaltic pump rotating speed of 10-20r/min (for example, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 r/min) and an air inlet temperature of 150-170 ℃ (for example, 150, 160 and 170 ℃), and carrying out granulation by using 75% ethanol solution of polyvinylpyrrolidone K30 with volume ratio of 5-15% (based on 75% ethanol solution, for example, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14% and 15%) as a wetting agent and a binding agent, so as a water extract granule of the hairyvein agrimony.
In one or more embodiments, the polygonum hydropiper aqueous extract granule is prepared by the following method: extracting a polygonum hydropiper medicinal material with water, concentrating and drying an extracting solution, and granulating by taking polyvinylpyrrolidone as an auxiliary material to obtain the polygonum hydropiper water extract granule.
In one or more embodiments, the polygonum hydropiper aqueous extract granules are prepared by the following method: adding water in an amount which is 8-12V/W times (for example, 8, 9, 10, 11, 12V/W times) of a polygonum hydropiper medicinal material, carrying out reflux extraction for 1-2 hours, extracting for 1-3 times (for example, 1, 2, 3 times), filtering, combining filtrates, concentrating under reduced pressure until the relative density is 1.05-1.10 (for example, 1.05, 1.06, 1.07, 1.08, 1.09, 1.10), carrying out spray drying at a peristaltic pump rotating speed of 10-20r/min (for example, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 r/min) and an air inlet temperature of 150-170 ℃ (for example, 150, 160, 170 ℃), and granulating by using a 75% ethanol solution of polyvinylpyrrolidone K30 in an amount which is 5-15 vol% (for example, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%) as a binding agent and a wetting agent to obtain the polygonum hydropiper water extract granule.
In one or more embodiments, the hedyotis diffusa water extract particles are prepared by the following method: extracting herba Hedyotidis Diffusae with water, concentrating the extractive solution, drying, adding polyvinylpyrrolidone as adjuvant, and granulating to obtain the water extract granule.
In one or more embodiments, the hedyotis diffusa water extract particles are prepared by the following method: taking oldenlandia diffusa medicinal material, adding 8-12V/W times (for example, 8, 9, 10, 11, 12V/W times) of water, carrying out reflux extraction for 1-2 hours, extracting for 1-3 times (for example, 1, 2, 3 times), filtering, combining filtrates, carrying out reduced pressure concentration until the relative density is 1.05-1.10 (for example, 1.05, 1.06, 1.07, 1.08, 1.09, 1.10), carrying out spray drying at a peristaltic pump rotating speed of 10-20r/min (for example, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 r/min) and an air inlet temperature of 150-170 ℃ (for example, 150, 160, 170 ℃), and carrying out granulation by using 75% ethanol solution of polyvinylpyrrolidone K30 with volume percent of 5-15% (for example, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%) as a wetting agent and a binder to obtain the oldenlandia water extract granule.
In one or more embodiments, the composition further includes 0.1 to 0.3 parts by weight (e.g., 0.1, 0.2, 0.3 parts by weight) sodium thiosulfate, 25 to 30 parts by weight (e.g., 25, 26, 27, 28, 29, 30 parts by weight) sodium glucoheptonate, 30 to 40 parts by weight (e.g., 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40 parts by weight) gluconolactone.
In one or more embodiments, the composition further includes 0.1 parts by weight sodium thiosulfate, 29 parts by weight sodium glucoheptonate, 30 parts by weight gluconolactone.
One or more embodiments of the present application provide a method for preparing a pharmaceutical composition for treating or preventing avian enterovirus syndrome, the method comprising:
mixing 50-100 parts (such as 50, 60, 70, 80, 90, 100 parts) of herba et Gemma Agrimoniae, 25-75 parts (such as 25, 35, 45, 55, 65, 75 parts) of herba Polygoni Caespitosi, and 70-140 parts (such as 70, 80, 90, 100, 110, 120, 130, 140 parts) of herba Hedyotidis Diffusae to obtain mixture.
In one or more embodiments, the method comprises: extracting herba et Gemma Agrimoniae 50-100 weight parts, herba Polygoni Hydropiperis 25-75 weight parts, and herba Hedyotidis Diffusae 70-140 weight parts to obtain extract.
In one or more embodiments, the method comprises: extracting herba et Gemma Agrimoniae 50-100 weight parts, herba Polygoni Hydropiperis 25-75 weight parts, and herba Hedyotidis Diffusae 70-140 weight parts with water to obtain water extract.
In one or more embodiments, the method comprises: mixing 10-20 parts by weight of herba et Gemma Agrimoniae water extract granule, 5-15 parts by weight of herba Polygoni Hydropiperis water extract granule, and 10-20 parts by weight of herba Hedyotidis Diffusae water extract granule.
In one or more embodiments, the method comprises: mixing 15 weight parts of hairyvein agrimony water extract particles, 10 weight parts of red-knees herb water extract particles and 15 weight parts of spreading hedyotis herb water extract particles.
In one or more embodiments, 0.1-0.3 parts by weight of sodium thiosulfate, 25-30 parts by weight of sodium glucoheptonate and 30-40 parts by weight of gluconolactone are added to the mixture, extract or water extract of agrimony, polygonum hydropiper and oldenlandia diffusa or mixed water extract granules.
In one or more embodiments, 0.1 parts by weight sodium thiosulfate, 29 parts by weight sodium glucoheptonate, 30 parts by weight gluconolactone are added to the mixture, extract or water extract of agrimony, polygonum hydropiper, oldenlandia diffusa, or mixed water extract granules.
In one or more embodiments, the agrimony medicinal material is extracted by water, the extracting solution is concentrated and dried, polyvinylpyrrolidone is used as an auxiliary material, and the granules are granulated to obtain the agrimony water extract granules.
In one or more embodiments, the agrimony is prepared by adding 8-12V/W times (e.g., 8, 9, 10, 11, 12V/W times) of water to agrimony, reflux-extracting for 1-2 hours, extracting for 1-3 times (e.g., 1, 2, 3 times), filtering, combining filtrates, concentrating under reduced pressure to a relative density of 1.05-1.10 (e.g., 1.05, 1.06, 1.07, 1.08, 1.09, 1.10), spray-drying at a peristaltic pump speed of 10-20r/min (e.g., 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 r/min) and an intake air temperature of 150 ℃ -170 ℃ (e.g., 150, 160, 170 ℃), and granulating with 5-15 vol% (e.g., 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%) of 75% ethanol solution of polyvinylpyrrolidone K30 as a wetting agent and a binder.
In one or more embodiments, the polygonum hydropiper medicinal material is extracted by water, the extracting solution is concentrated and dried, polyvinylpyrrolidone is used as an auxiliary material, and the granules are granulated to obtain the polygonum hydropiper water extract granules.
In one or more embodiments, the polygonum hydropiper linn is prepared by adding 8-12V/W times (for example, 8, 9, 10, 11, 12V/W times) of water, reflux-extracting for 1-2 hours, extracting for 1-3 times (for example, 1, 2, 3 times), filtering, combining filtrates, concentrating under reduced pressure to relative density of 1.05-1.10 (for example, 1.05, 1.06, 1.07, 1.08, 1.09, 1.10), spray-drying at peristaltic pump speed of 10-20r/min (for example, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 r/min) and air inlet temperature of 150 ℃ -170 ℃ (for example, 150, 160, 170 ℃), and granulating with 5-15 vol% (for example, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%) of 75% ethanol solution of polyvinylpyrrolidone K30 as wetting agent and binder.
In one or more embodiments, the oldenlandia diffusa medicinal material is extracted by water, the extracting solution is concentrated and dried, polyvinylpyrrolidone is used as an auxiliary material, and the particles are granulated to obtain the oldenlandia diffusa water extract particles.
In one or more embodiments, the hedyotis diffusa willd is added with 8-12V/W times (for example, 8, 9, 10, 11, 12V/W times) of water, reflux extraction is performed for 1-2 hours, extraction is performed for l-3 times (for example, 1, 2, 3 times), filtration is performed, filtrates are combined, reduced pressure concentration is performed until the relative density is 1.05-1.10 (for example, 1.05, 1.06, 1.07, 1.08, 1.09, 1.10), spray drying is performed at a peristaltic pump rotating speed of 10-20r/min (for example, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 r/min) and an air inlet temperature of 150 ℃ -170 ℃ (for example, 150, 160, 170 ℃), 75% ethanol solution of polyvinylpyrrolidone K30 is adopted as a wetting agent and a binder, and granules are obtained by granulating the hedyotis diffusa willd by using 5-15 vol% (for example, 5%, 7%, 8%, 9%, 1%, 11%, 5% of ethanol solution of the 75% ethanol solution of the polyvinylpyrrolidone K30 as a wetting agent and the binder.
In one or more embodiments, sodium thiosulfate, sodium glucoheptonate, gluconolactone are added to the aqueous extract or aqueous extract granules of agrimony, polygonum hydropiper, oldenlandia diffusa.
One or more embodiments of the present application provide a use of a pharmaceutical composition of the present application for the manufacture of a medicament for treating or preventing avian enterovirus syndrome.
One or more embodiments of the present application provide a use of the pharmaceutical composition of the present application in the preparation of a medicament for treating or preventing intestinal infectious diseases of birds caused by abnormal proliferation of bacterial, protozoal, or viral infections.
In one or more embodiments, the avian is a chicken.
In one or more embodiments, the pharmaceutical composition of the present application is prepared by pulverizing and mixing the following raw materials in parts by weight: 50-100 parts of hairyvein agrimony, 25-75 parts of red-knees herb and 70-140 parts of oldenlandia diffusa. The composition also comprises 0.1-0.3 weight part of sodium thiosulfate, 25-30 weight parts of sodium glucoheptonate and 30-40 weight parts of gluconolactone; for example, 0.1 part by weight of sodium thiosulfate, 29 parts by weight of sodium glucoheptonate, 30 parts by weight of gluconolactone.
In one or more embodiments, the pharmaceutical composition of the application can clear away heat and toxic materials, kill parasites and reduce swelling, stop bleeding and stop diarrhea, improve the environment in intestinal tracts, improve the immunity of organisms, effectively remove the pathological factors of damp-heat accumulation and qi and blood stagnation, achieve the effect of effectively treating the enterovirus syndromes of poultry, and has remarkable curative effect advantages of causing anal swelling to diarrhea. The medicine composition adopts the traditional Chinese medicine water extract particles to match with nutrient components, has good water solubility, and meets the requirement of the administration characteristic of modern large-scale aquaculture waterlines.
The herba et Gemma Agrimoniae is dried aerial part of Agrimonia pilosa Ledeb of Rosaceae.
Herba Polygoni Hydropiperis is whole plant or root and leaf of Polygonum hydropiper L.and Polygonum flaccidum Meism of Polygonum of Polygonaceae.
Herba Hedyotidis Diffusae is dried whole plant of Hedyotis diffusa Hedyotis diffussa Willd.
In one or more embodiments, the volume of the V/W fold represents the ratio of the volume of water added to the drug to the weight of the drug.
In one or more embodiments, the agrimonia pilosa extract, the agrimonia pilosa water extract, and the agrimonia pilosa water extract particles contain agrimonol and quercetin, and the agrimonol has a remarkable inhibitory activity against staphylococcus aureus, bacillus, nocardia, and the like, and has an insect repellent effect. Quercetin, as a flavonoid compound naturally existing in the nature, has stable and strong biological activity and wide pharmacological action of resisting inflammation, resisting virus, protecting cardiovascular system, inhibiting immunity and the like. In one or more embodiments, the polygonum hydropiper extract, the polygonum hydropiper water extract and the polygonum hydropiper water extract granules contain flavonoid compounds such as rutin, quercetin, kaempferol and the like and sesquiterpene compounds such as polygonaldehyde and the like, and the flavonoid compounds have stable and strong biological activity and wide pharmacological action such as anti-inflammation, antivirus, cardiovascular protection, immunosuppression and the like. The diterpene compounds such as polygodial have inhibitory effect on Bacillus dysenteriae, salmonella typhi, diptheria bacillus, staphylococcus aureus, and hemolytic streptococcus, and can also repel parasites in vivo and in vitro, and inhibit infection of some fungi.
In one or more embodiments, the oldenlandia diffusa extract, the oldenlandia diffusa water extract and the oldenlandia diffusa water extract particles contain flavonoids, polysaccharides, terpenoids and sterols, the flavonoids have obvious bacteriostatic action on bacillus subtilis, escherichia coli and staphylococcus aureus, and have anti-inflammatory action, and the polysaccharides have antiviral action; terpenoids and sterols have effects of resisting bacterial invasion, relieving inflammation, relieving pain, resisting colon cancer and regulating immunity.
In one or more embodiments, the pharmaceutical composition for preventing or treating avian enterovirus syndrome of the present application comprises the following raw material medicines in parts by weight: 10-20 parts of hairyvein agrimony water extract particles, 5-15 parts of red-knees herb water extract particles, 10-20 parts of spreading hedyotis herb water extract particles, 0.1-0.3 part of sodium thiosulfate, 25-30 parts of sodium glucoheptonate and 30-40 parts of gluconolactone.
In one or more embodiments, the pharmaceutical composition for preventing and treating avian enterovirus syndrome of the present application comprises the following raw material medicine components in parts by weight: 15 parts of hairyvein agrimony water extract particles, 10 parts of red-knees herb water extract particles, 15 parts of spreading hedyotis herb water extract particles, 0.1 part of sodium thiosulfate, 29 parts of sodium glucoheptonate and 30 parts of gluconolactone.
In one or more embodiments, the preparation method of the pharmaceutical composition for preventing and treating avian enterovirus syndrome of the present application includes a method for preparing the water extract granule and a method for preparing the composition, such as:
step 1, preparing hairyvein agrimony water extract particles, red-knees herb water extract particles and spreading hedyotis herb water extract particles:
step 1.1, taking 5000g of hairyvein agrimony decoction pieces, adding 8-12V/W times of water, performing reflux extraction for 1-2 hours, extracting for 1, 2 or 3 times, filtering, combining filtrates, concentrating under reduced pressure until the relative density is 1.05-1.10, performing spray drying at the rotating speed of a peristaltic pump of 10-20r/min and the air inlet temperature of 150-170 ℃, adding 75% ethanol solution of 5-15% polyvinylpyrrolidone K30 as a wetting agent and an adhesive, granulating, and preparing into 1000g of hairyvein agrimony water extract granules; the agrimony water extract granule is brown to brownish red; light smell, slightly bitter taste;
step 1.2, taking 5000g of polygonum hydropiper decoction pieces, adding water of which the amount is 8-12V/W times of the weight of the polygonum hydropiper decoction pieces, performing reflux extraction for 1-2 hours, extracting for 1, 2 or 3 times, filtering, combining filtrates, concentrating under reduced pressure until the relative density is 1.05-1.10, performing spray drying at the rotating speed of a peristaltic pump of 10-20r/min and the air inlet temperature of 140-160 ℃, adding 75% ethanol solution of 5-15% polyvinylpyrrolidone K30 as a wetting agent and an adhesive, granulating, and preparing into 1000g of polygonum hydropiper water extract granules;
step 1.3, 7000g of oldenlandia diffusa decoction pieces are taken, water which is 8-12V/W times of the oldenlandia diffusa decoction pieces is added, reflux extraction is carried out for 1-2 hours, extraction is carried out for 1, 2 or 3 times, filtration is carried out, filtrate is combined, reduced pressure concentration is carried out until the relative density is 1.05-1.10, spray drying is carried out at the rotating speed of a peristaltic pump of 10-20r/min and the air inlet temperature of 140-160 ℃, 75% ethanol solution of 5-15% polyvinylpyrrolidone K30 is added as a wetting agent and an adhesive, granulation is carried out, and 1000g of oldenlandia diffusa water extract particles are obtained;
step 2, preparing a pharmaceutical composition:
weighing 15 parts of hairyvein agrimony water extract particles, 10 parts of red-knees herb water extract particles, 15 parts of spreading hedyotis herb water extract particles, 0.1 part of sodium thiosulfate, 28 parts of sodium glucoheptonate and 30 parts of gluconolactone according to parts by weight; mixing to obtain the medicinal composition for preventing and treating enterovirus syndrome of poultry.
In one or more embodiments, the pharmaceutical composition of the present application is prepared by mixing water extract granules of traditional Chinese medicine with adjuvant having specific bioactivity, and administering by drinking water, wherein the therapeutic addition amount is 1k per time g The pharmaceutical composition of the present application is orally administered at 0.1g for 3-5 days for 1 course of treatment.
The pharmaceutical composition of one or more embodiments of the application can effectively prevent and treat the avian enterovirus syndrome, achieves the effect of treating both symptoms and root causes, and fundamentally solves the intestinal health problem of the avian.
In one or more embodiments, the pharmaceutical compositions and methods of making the same of the present application have at least one of the following beneficial effects:
firstly, the traditional Chinese medicine composition is prepared by selecting hairyvein agrimony, red-knees herb and spreading hedyotis herb according to the guidance of the traditional Chinese veterinary medicine theory and aiming at the infection characteristics of multiple causes of enterotoxin syndrome and matching with sodium thiosulfate, sodium glucoheptonate, gluconolactone and other components. The polygonum hydropiper has the functions of dispelling wind and promoting diuresis, eliminating stasis and relieving pain, detoxifying and reducing swelling, killing parasites and relieving itching. Herba Hedyotidis Diffusae has effects of clearing away heat and toxic materials, relieving pain, dispersing pathogen accumulation, promoting urination, and removing dampness; secondly, the auxiliary material components also have pharmacological activity and improve the treatment effect of the main drug, wherein, the gluconolactone and the sodium glucoheptonate are decomposed to generate gluconic acid and glucoheptonate after entering the body, have prebiotic effect and play a role in bidirectional regulation, thereby not only promoting the proliferation of probiotics, but also inhibiting the abnormal metabolic activity of harmful bacteria and improving the health level of the intestinal tract by regulating the environment in the intestinal tract; third, sodium thiosulfate increases the thiocyanate-producing enzyme content by supplying elemental sulfur to eliminate toxic substances and the like. The traditional Chinese medicine composition has the effects of killing pests and reducing swelling, clearing heat and removing toxicity, stopping bleeding and dysentery, improving the internal environment of intestinal tracts, improving the immunity of organisms, effectively inhibiting the abnormal metabolic activity of germs, fungi, protozoa and viruses, achieving the purpose of curing the enterotoxin syndrome of poultry, and simultaneously has remarkable curative effect advantage on anal swelling caused by diarrhea.
Secondly, according to the characteristics of each component in the formula, the preparation method adopts the modern extraction technology to prepare the formula particles, the effective components are fully dissolved out, the quality control is carried out by adopting a characteristic map, the uniformity and the controllability of the preparation are achieved, the curative effect is effectively ensured, the large-scale production is easy to form, and meanwhile, the formula particles adopt a water extraction process, have good solubility and are suitable for the administration requirement of modern large-scale cultivation waterlines.
Thirdly, the traditional Chinese medicine composition has the characteristics of obvious curative effect, no drug resistance, no drug residue and the like, can improve the internal environment of intestinal tracts of chickens, improves the immunity of the chickens, has important significance for reducing the use of antibiotics in the feeding process of the chickens, improving the health condition of chicken flocks and improving the food safety of the chicken and the products thereof, and has considerable economic benefit and social prospect.
Drawings
FIG. 1 is a characteristic HPLC chromatogram of Agrimonia pilosa extract particles.
FIG. 2 is a characteristic HPLC chromatogram of Polygonum hydropiper extract granules.
Fig. 3 is a characteristic HPLC profile of oldenlandia diffusa extract particles.
Detailed Description
In order to make the objects, technical solutions and advantages of the present application more apparent, the present application is described in further detail below. It should be understood, however, that the description herein of specific embodiments is only intended to illustrate the invention and not to limit the scope of the application. The test materials, reagents and the like used in the following examples are commercially available unless otherwise specified.
Example 1 preparation of granule of water extract of Agrimonia pilosa
Taking 5000g of hairyvein agrimony decoction pieces, adding water which is 10V/W times of the hairyvein agrimony decoction pieces, carrying out reflux extraction for 1 hour, extracting for 2 times, filtering, combining filtrates, carrying out reduced pressure concentration until the relative density is 1.08, carrying out spray drying at the rotating speed of a peristaltic pump of 15r/min and the air inlet temperature of 160 ℃, adding 75% ethanol solution which adopts 10% polyvinylpyrrolidone K30 as a wetting agent and an adhesive, granulating, and preparing 1000g of the hairyvein agrimony water extract granules. The agrimony water extract granule has the characteristics of brown to brownish red granules; light smell, slightly bitter taste. The HPLC characteristic spectrum of qualitative identification of herba et Gemma Agrimoniae water extract granule is shown in figure 1.
Example 2 preparation of Polygonum hydropiper Water extract granule
Taking 5000g of polygonum hydropiper decoction pieces, adding water of which the amount is 10V/W times of the decoction pieces, carrying out reflux extraction for 1 hour, extracting for 2 times, filtering, combining filtrates, carrying out reduced pressure concentration until the relative density is 1.05, carrying out spray drying at the rotation speed of a peristaltic pump of 15r/min and the air inlet temperature of 160 ℃, adding 75% ethanol solution of 10% polyvinylpyrrolidone K30 as a wetting agent and an adhesive, granulating, and preparing 1000g of the polygonum hydropiper water extract granule. The characteristic of the polygonum hydropiper water extract granule is a brown yellow to brown granule; light smell, slightly bitter taste. The HPLC characteristic spectrum of the qualitative identification of herba Hedyotidis Diffusae water extract granule is shown in figure 2.
Example 3 preparation of granules of aqueous extract of Oldenlandia diffusa
Further, taking 5000g of spreading hedyotis herb decoction pieces, adding water of which the amount is 10V/W times of the spreading hedyotis herb decoction pieces, carrying out reflux extraction for 1 hour, extracting for 2 times, filtering, combining filtrates, concentrating under reduced pressure until the relative density is 1.08, carrying out spray drying at the rotation speed of a peristaltic pump of 20r/min and the air inlet temperature of 140 ℃, adding 75% ethanol solution of 10% polyvinylpyrrolidone K30 serving as a wetting agent and an adhesive, granulating, and preparing into 1000g of spreading hedyotis herb water extract granules. The properties of the spreading hedyotis herb water extract granules are from grayish brown to brown granules; light smell, slightly bitter taste. The HPLC characteristic spectrum of the qualitative identification of the herba Hedyotidis Diffusae water extract granule is shown in figure 3.
EXAMPLE 4 preparation of pharmaceutical composition
Preparation example 1
The preparation method of the pharmaceutical composition comprises the following steps: weighing 10 kg of hairyvein agrimony water extract particles, 15 kg of red-knees herb water extract particles, 20 kg of spreading hedyotis herb water extract particles, 0.2 kg of sodium thiosulfate, 30 kg of sodium glucoheptonate and 35 kg of gluconolactone according to the proportion of a prescription, and uniformly mixing to obtain the pharmaceutical composition.
Preparation example 2
The preparation method of the pharmaceutical composition comprises the following steps: weighing 15 kg of hairyvein agrimony water extract particles, 10 kg of red-knees herb water extract particles, 15 kg of spreading hedyotis herb water extract particles, 0.1 kg of sodium thiosulfate, 29 kg of sodium glucoheptonate and 30 kg of gluconolactone according to the proportion of a prescription, and uniformly mixing to obtain the pharmaceutical composition.
Preparation example 3
The preparation method of the pharmaceutical composition comprises the following steps: weighing 20 kg of hairyvein agrimony water extract particles, 5 kg of polygonum hydropiper water extract particles, 10 kg of spreading hedyotis herb water extract particles, 0.3 kg of sodium thiosulfate, 25 kg of sodium glucoheptonate and 40 kg of gluconolactone according to the proportion of a prescription, and uniformly mixing to obtain the pharmaceutical composition.
Preparation example 4
The preparation method of the pharmaceutical composition comprises the following steps: weighing 60 kg of hairyvein agrimony water extract particles, 45 kg of red-knees herb water extract particles and 60 kg of spreading hedyotis herb water extract particles according to the proportion of the prescription, and uniformly mixing to obtain the medicinal composition.
Preparation example 5
The preparation method of the pharmaceutical composition comprises the following steps: weighing 3 kg of sodium thiosulfate, 77 kg of sodium glucoheptonate and 90 kg of gluconolactone according to the proportion of the prescription, and uniformly mixing to obtain the pharmaceutical composition.
Effects of the embodiment
To demonstrate the effect of the pharmaceutical composition of the present application on the enterovirus syndrome in birds, the pharmaceutical composition of the present application was tested for its pharmaceutical activity.
1) Test drugs: a pharmaceutical composition of the present application.
2) Design of experiments
The experiment is carried out in a large-scale chicken farm in Yuzhong county of Gansu province, 25-33 days old AA chickens diagnosed with enterovirus syndrome are selected as study objects and are randomly divided into 4 groups, wherein 200 AA chickens in the experiment 1 group (preparation example 1), 200 AA chickens in the experiment 2 group (preparation example 2), 200 AA chickens in the experiment 3 group (preparation example 3), 200 AA chickens in the experiment 4 group (preparation example 4) and 200 AA in the experiment 5 group (preparation example 5) are orally taken according to the weight of 1kg, and the medicine composition is mixed and drunk once a day and continuously administered for 5 days. The control group was 5% enrofloxacin oral liquid, 0.5g per 1kg of water, once a day, and administered continuously for 5 days. After the treatment starts, the body change condition and the death animal distribution of the sick chickens are recorded every day, the treatment effect is counted 7 days after the treatment, and the treatment effect judgment standard is as follows:
recovery means that the affected chickens recover from spirit and normal ingestion within 7 days after the first administration, and feces are normal without overdosing.
The effective means that the sick chickens recover from spirits and eating within 7 days after the first administration, and the phenomenon of overdose does not exist, so that the excrement is not shaped.
The ineffectiveness means that the sick chickens have no improvement in spirit, ingestion and diarrhea or even die within 7 days after the first medication.
3) Data statistics
By using
(Version 17.0) for data analysis. Chi fang test is carried out to evaluate the cure rate and the total effective rate of the test group and the control group. Double-sided tests are adopted, and the difference of the tests is considered to have statistical significance when P is less than 0.05. The measured data of different test groups are statistically described by mean + -std.
4) As a result, the
4.1 therapeutic results for the pharmaceutical compositions of the present application
The clinical effect of the pharmaceutical composition for treating the enterovirus syndrome of the chickens is shown in table 1. Compared with a control group, the cure rate and the total effective rate of the pharmaceutical composition (the test 1-3 groups) are obviously improved, the difference is extremely obvious (P is less than 0.01), and no obvious difference exists among the test 1-3 groups (P is more than 0.05). The results show that the pharmaceutical composition can effectively treat the enterovirus syndrome in chickens.
TABLE 1 results of clinical efficacy test of pharmaceutical composition for treating enterovirus syndrome in chicken
Note: the differences were not significant for the same column data with the same letter shoulder (P > 0.05), the difference is significant when the letters are marked with different lower case letters (P < 0.05), and the difference is significant when the letters are marked with different upper case letters (P < 0.01). The same applies below.
4.2 clinical evaluation of synergistic action of the main drug and the auxiliary materials in the pharmaceutical composition
The clinical evaluation results of the synergistic effect of the main drug and the auxiliary materials in the pharmaceutical composition are shown in table 2. Compared with a control group, the cure rate and the total effective rate of the test 2 group and the test 4 group are obviously improved, the difference is extremely obvious (P is less than 0.01), the cure rate and the total effective rate of the test 5 group are obviously reduced, and the difference is extremely obvious (P is less than 0.01). Compared with the test 5 groups, the cure rate and the total effective rate of the test 2 group and the test 4 group are obviously improved, and the difference is extremely obvious (P is less than 0.01). Meanwhile, the cure rate and the total effective rate of the 2 groups are higher than those of the 4 groups, but the difference is not significant (P > 0.05). The results show that the compatibility of the hairyvein agrimony formula particles, the red-knees herb formula particles and the spreading hedyotis herb formula particles can effectively treat the enterovirus syndrome, and the sodium thiosulfate, the gluconolactone and the sodium glucoheptonate can synergistically enhance the treatment effect of the traditional Chinese medicine formula.
TABLE 2 clinical evaluation results of synergistic effect of main drug and adjuvant in pharmaceutical composition
Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art will recognize that changes may be made in the form and details of the embodiments described herein without departing from the spirit and scope of the invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present application.
Claims (10)
1. The pharmaceutical composition for treating or preventing the avian enterovirus syndrome is prepared from the following raw materials in parts by weight: 50-100 parts of hairyvein agrimony, 25-75 parts of red-knees herb and 70-140 parts of spreading hedyotis herb;
preferably, the pharmaceutical composition is extracted from the following raw materials in parts by weight: 50-100 parts of hairyvein agrimony, 25-75 parts of red-knees herb and 70-140 parts of oldenlandia diffusa;
more preferably, the pharmaceutical composition is prepared by extracting the following raw materials in parts by weight with water: 50-100 parts of hairyvein agrimony, 25-75 parts of red-knees herb and 70-140 parts of spreading hedyotis herb.
2. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises 10-20 parts by weight of agrimony water extract particles, 5-15 parts by weight of polygonum hydropiper water extract particles, 10-20 parts by weight of oldenlandia diffusa water extract particles; preferably, the granule comprises 15 weight parts of hairyvein agrimony water extract granules, 10 weight parts of red-knees herb water extract granules and 15 weight parts of spreading hedyotis herb water extract granules.
3. The pharmaceutical composition of claim 2, wherein
The hairyvein agrimony water extract particles are prepared by the following method: extracting herba et Gemma Agrimoniae with water, concentrating the extractive solution, drying, adding polyvinylpyrrolidone as adjuvant, and granulating to obtain herba et Gemma Agrimoniae water extract granule; preferably, taking a hairyvein agrimony medicinal material, adding 8-12V/W times of water, carrying out reflux extraction for 1-2 hours, extracting for 1-3 times, filtering, combining filtrates, concentrating under reduced pressure until the relative density is 1.05-1.10, carrying out spray drying at the rotating speed of a peristaltic pump of 10-20r/min and the air inlet temperature of 150-170 ℃, and granulating by adopting a 75% ethanol solution of 5-15 vol% polyvinylpyrrolidone K30 as a wetting agent and an adhesive to obtain the hairyvein agrimony water extract particles;
the polygonum hydropiper water extract granule is prepared by the following method: extracting a polygonum hydropiper medicinal material with water, concentrating and drying an extracting solution, and granulating by taking polyvinylpyrrolidone as an auxiliary material to obtain the polygonum hydropiper water extract granules; preferably, taking a polygonum hydropiper medicinal material, adding water with the volume of 8-12V/W times, carrying out reflux extraction for 1-2 hours, extracting for 1-3 times, filtering, combining filtrates, concentrating under reduced pressure until the relative density is 1.05-1.10, carrying out spray drying at the rotating speed of a peristaltic pump of 10-20r/min and the air inlet temperature of 150-170 ℃, and granulating by using 75% ethanol solution of 5-15 vol% polyvinylpyrrolidone K30 as a wetting agent and an adhesive to obtain the polygonum hydropiper water extract granules;
the oldenlandia water extract granule is prepared by the following method: extracting herba Hedyotidis Diffusae with water, concentrating and drying the extractive solution, and granulating with polyvinylpyrrolidone as adjuvant to obtain herba Hedyotidis Diffusae water extract granule; preferably, taking the oldenlandia diffusa medicinal material, adding 8-12V/W times of water, carrying out reflux extraction for 1-2 hours, extracting for 1-3 times, filtering, combining filtrates, concentrating under reduced pressure until the relative density is 1.05-1.10, carrying out spray drying at the rotation speed of a peristaltic pump of 10-20r/min and the air inlet temperature of 150-170 ℃, and granulating by using 75% ethanol solution of 5-15 vol% polyvinylpyrrolidone K30 as a wetting agent and an adhesive to obtain the oldenlandia diffusa water extract particles.
4. The pharmaceutical composition of claim 1, further comprising 0.1 to 0.3 parts by weight of sodium thiosulfate, 25 to 30 parts by weight of sodium glucoheptonate, 30 to 40 parts by weight of gluconolactone; preferably 0.1 parts by weight of sodium thiosulfate, 29 parts by weight of sodium glucoheptonate and 30 parts by weight of gluconolactone.
5. A method for preparing a pharmaceutical composition for treating or preventing avian enterovirus syndrome, the method comprising:
mixing 50-100 parts by weight of hairyvein agrimony, 25-75 parts by weight of red-knees herb and 70-140 parts by weight of spreading hedyotis herb to obtain a mixture; or
Extracting 50-100 parts by weight of hairyvein agrimony, 25-75 parts by weight of red-knees herb and 70-140 parts by weight of spreading hedyotis herb to obtain extracts; preferably, the aqueous extract is obtained by extraction with water; or
Mixing 10-20 parts by weight of hairyvein agrimony water extract particles, 5-15 parts by weight of polygonum hydropiper water extract particles and 10-20 parts by weight of spreading hedyotis herb water extract particles; preferably 15 weight parts of hairyvein agrimony water extract particles, 10 weight parts of red-knees herb water extract particles and 15 weight parts of spreading hedyotis herb water extract particles.
6. The preparation method according to claim 5, wherein 0.1 to 0.3 part by weight of sodium thiosulfate, 25 to 30 parts by weight of sodium glucoheptonate and 30 to 40 parts by weight of gluconolactone are added to the mixture, extract or water extract of Agrimonia pilosa, polygonum hydropiper and Hedyotis diffusa or the mixed water extract granule; preferably 0.1 parts by weight of sodium thiosulfate, 29 parts by weight of sodium glucoheptonate and 30 parts by weight of gluconolactone.
7. The method according to claim 5, wherein
Extracting herba et Gemma Agrimoniae with water, concentrating the extractive solution, drying, adding polyvinylpyrrolidone as adjuvant, and granulating to obtain herba et Gemma Agrimoniae water extract granule; preferably, taking a hairyvein agrimony medicinal material, adding 8-12V/W times of water, carrying out reflux extraction for 1-2 hours, extracting for 1-3 times, filtering, combining filtrates, concentrating under reduced pressure until the relative density is 1.05-1.10, carrying out spray drying at the rotating speed of a peristaltic pump of 10-20r/min and the air inlet temperature of 150-170 ℃, and granulating by adopting a 75% ethanol solution of 5-15 vol% polyvinylpyrrolidone K30 as a wetting agent and an adhesive to obtain the hairyvein agrimony water extract particles;
extracting a polygonum hydropiper medicinal material with water, concentrating and drying an extracting solution, and granulating by taking polyvinylpyrrolidone as an auxiliary material to obtain the polygonum hydropiper water extract granules; preferably, taking a polygonum hydropiper medicinal material, adding water with the volume of 8-12V/W times, carrying out reflux extraction for 1-2 hours, extracting for 1-3 times, filtering, combining filtrates, concentrating under reduced pressure until the relative density is 1.05-1.10, carrying out spray drying at the rotating speed of a peristaltic pump of 10-20r/min and the air inlet temperature of 150-170 ℃, and granulating by using 75% ethanol solution of 5-15 vol% polyvinylpyrrolidone K30 as a wetting agent and an adhesive to obtain the polygonum hydropiper water extract granules;
extracting herba Hedyotidis Diffusae with water, concentrating the extractive solution, drying, adding polyvinylpyrrolidone as adjuvant, and granulating to obtain herba Hedyotidis Diffusae water extract granule; preferably, taking the oldenlandia diffusa medicinal material, adding 8-12V/W times of water, performing reflux extraction for 1-2 hours, extracting for 1-3 times, filtering, combining filtrates, concentrating under reduced pressure until the relative density is 1.05-1.10, performing spray drying at the rotating speed of a peristaltic pump of 10-20r/min and the air inlet temperature of 150-170 ℃, and granulating by using 75% ethanol solution of 5-15 vol% polyvinylpyrrolidone K30 as a wetting agent and an adhesive to obtain the oldenlandia diffusa water extract particles;
optionally, sodium thiosulfate, sodium glucoheptonate and gluconolactone are added into the water extract or water extract granules of the agrimony, the red-knees herb and the oldenlandia diffusa.
8. Use of a pharmaceutical composition according to any one of claims 1 to 4 in the manufacture of a medicament for the treatment or prevention of enterovirus syndrome in an avian.
9. Use of the pharmaceutical composition of any one of claims 1-4 for the preparation of a medicament for the treatment or prevention of intestinal infectious diseases in avians caused by abnormal proliferation of bacterial, protozoal, or viral infections.
10. The use according to claim 8 or 9, wherein the avian is a chicken.
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| CN104887890A (en) * | 2015-06-11 | 2015-09-09 | 山东新希望六和集团有限公司 | Medicine composition for treating white scour of chicken and preparation method thereof |
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| Title |
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| 陈鹏举等: "《禽病诊治原色图谱》", vol. 2, 河南科学技术出版社, pages: 305 * |
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