CN103127198B - Combined drug for treating piglet's yellow-white dysentery - Google Patents
Combined drug for treating piglet's yellow-white dysentery Download PDFInfo
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Abstract
The invention provides an application of root of Chinese barberry and Portulaca oleracea in preparation of a combined drug for treating piglet's yellow-white dysentery. The invention also provides the combined drug for treating piglet's yellow-white dysentery and its purpose. According to the invention, root of Chinese barberry and Portulaca oleracea are combined, the Escherichia coli resistance and piglet's yellow-white dysentery treatment effects are obviously superior to the unit drug under equal dosage, the synergistic interaction effect can be performed, and a novel veterinary drug selectivity is provided. The drug can be prepared to a micro-capsule preparation, the bitter flavor of root of Chinese barberry is covered, the compliance and stability of the drug can be increased, the slow release and controlled release effect is reached, and a liquid drug is solidified and is convenient for application and storage.
Description
Technical field
The present invention relates to the combination medicine for the treatment of yellow and white dysentery of piglet.
Background technology
Yellow and white dysentery of piglet, is caused by escherichia coli, acutely to suffer from diarrhoea, discharges a class acute height lethal infectious intestinal disease that yellow or yellow-white watery stools and rapid dehydration are feature.Pig within 1 week age is multiple, and 1-3 age in days is the most common.Brood piglet sickness rate is very high, is everlasting more than 90%, and mortality rate is also very high, and even whole nest is dead sometimes.Carry out prevention and therapy about this sick main medicine that adopts at present, also have vaccine list marketing, but do not obtain good preventive effect because e. coli serotype is more and various places serotype is not the same.
In the medicine selected at present, still based on chemicalses such as quinolones, aminoglycoside and sulfonamides, due to the long-term medication lack of standardization of veterinary clinic, a large amount of fastbacteria is caused to produce, make these conventional chemicals effects poor, what have even reaches 100% drug resistance, and this brings huge difficulty to this disease of clinic control.Therefore, in conjunction with Chinese veterinarian's theory, exploitation one is treated yellow and white dysentery of piglet effect good herbal medicine product and is just seemed particularly important.
Summary of the invention
The object of the present invention is to provide a kind of combination medicine for the treatment of yellow and white dysentery of piglet.Another object of the present invention is to provide a kind of medical composition and its use for the treatment of yellow and white dysentery of piglet.
The invention provides Radix Berberidis and the purposes of Herba Portulacae in the combination medicine of preparation treatment yellow and white dysentery of piglet.
Wherein, the weight proportion of described Radix Berberidis and Herba Portulacae is (1 ~ 3): (1 ~ 3).
Further, the weight proportion of described Radix Berberidis and Herba Portulacae is 1:2.
Present invention also offers a kind of pharmaceutical composition for the treatment of yellow and white dysentery of piglet, it is the preparation be prepared from by the crude drug of following weight proportion:
Radix Berberidis 1 ~ 3 part, Herba Portulacae 1 ~ 3 part.
Further, it is the preparation be prepared from by the crude drug of following weight proportion:
Radix Berberidis 1 part, Herba Portulacae 2 parts.
Wherein, described pharmaceutical composition be with the water of the medicated powder of the crude drug of described weight proportion or crude drug or extractive with organic solvent for active component, add the preparation that pharmaceutically conventional adjuvant or complementary composition are prepared from.
Wherein, described preparation is oral agents.
Further, described oral agents is powder, tablet, pill, capsule, microcapsule, granule, medicinal cake or liquid preparation.
Further, described microcapsule is prepared from by the supplementary material containing, for example lower weight proportion:
The capsule heart and capsule material mass ratio are 1:(1 ~ 5);
Wherein, the capsule heart is water or the extractive with organic solvent of Radix Berberidis and Herba Portulacae; Capsule material is one or more the combination in gelatin, arabic gum, alginate, chitosan, carboxymethyl cellulose salt, ethyl cellulose, methylcellulose, hypromellose.
Further, described capsule material is gelatin: arabic gum=(1 ~ 3): (1 ~ 3) w/w.
Further, the preparation method of described extract is as follows: get Radix Berberidis: Herba Portulacae=(1 ~ 3): (1 ~ 3) w/w, and Herba Portulacae decocts with water, collecting decoction, and filter, filtrate is concentrated into the clear paste that relative density is 1.35, for subsequent use; Radix Berberidis adds 50%v/v ethanol extraction, and merge extractive liquid, filters, and filtrate is concentrated into the clear paste that relative density is 1.35, adds above-mentioned Herba Portulacae clear paste, obtains crude drug extract.
Present invention also offers the preparation method of described microcapsule, its capsule material is gelatin and arabic gum, and concrete operation step is as follows:
(1) gelatin and arabic gum is taken, respectively the solution being made into mass concentration 5 ~ 10% soluble in water, 40 ~ 60 DEG C of constant temperature water baths; Weighting raw materials extract, fully mixes with part of gelatin solution, then with gumwater with remain gelatin solution and mix homogeneously;
(2) keep temperature to be 40 ~ 60 DEG C, adjust pH to 3.6 ~ 4.5 with aqueous acetic acid, continue to stir, when crude drug extract tunicle wraps up, add water, continue to stir and stop heating, when temperature is reduced to below 25 DEG C, move to ice-water bath continue to stir, then adjust pH to 8 ~ 9 with sodium carbonate, continue to stir, add cross-linking agent again, crosslinking curing, centrifugalize, solid content is washed to weakly acidic pH, drying, to obtain final product.
Preferably, described cross-linking agent is formaldehyde.
Present invention also offers the purposes of above-mentioned pharmaceutical composition in the medicine of preparation Chinese People's Anti-Japanese Military and Political College enterobacteria, treatment yellow and white dysentery of piglet.
Chinese veterinarian's theory is thought, mostly yellow and white dysentery of piglet is with the damp and hot heresy of carcass impression, injure taste, invade in epidemic disease poison, cause the muddy part of intestinal, the wet bet of water and rawly to have loose bowels, doctor trained in Western medicine theory is thought to cause because of coli-infection, and in therefore combining, doctor trained in Western medicine is theoretical, consulted lot of documents, first-selected heat clearing and damp drying, has the Chinese medicine Radix Berberidis of certain fungistatic effect and Herba Portulacae in vitro as prescription foundation.
Herba Portulacae is the dry aerial parts of portulacaceous plant Herba Portulacae, sour, cold, returns liver, large intestine channel.There is heat-clearing and toxic substances removing, effect of eliminating pathogenic heat from blood to cure dysentery.Radix Berberidis is the dry root that Berberidaceae plant intends that porcupine quill, berberis poiretii or spoonleaf barbarry herb etc. belong to several plants together, bitter in the mouth, cold in nature, returns liver, stomach, large intestine channel, has heat clearing and damp drying, effect of eliminating fire and detoxication.
The present invention is by after Radix Berberidis and Herba Portulacae conbined usage, and its Chinese People's Anti-Japanese Military and Political College enterobacteria is obviously better than the unit medicament under Isodose with the effect for the treatment of yellow and white dysentery of piglet, played synergistic function, provides a kind of new veterinary drug and selects.Meanwhile, medicine is prepared into microcapsule formulation by the present invention, masks the bitterness of Radix Berberidis, improves compliance and the stability of medicine, reaches the effect of slow release or controlled release, and makes liquid drug solid state be convenient to application and storage.
Detailed description of the invention
The preparation of embodiment 1 medicine of the present invention
Get Herba Portulacae 100g, Radix Berberidis 50g.Herba Portulacae decocts with water secondary, 2 hours first times, second time 1 hour, collecting decoction, and filter, it is 1.35 that filtrate is concentrated into relative density, is Herba Portulacae extract; Radix Berberidis adds 50% alcohol reflux twice, each one hour, and merge and filter, it is 1.35 that filtrate is concentrated into relative density, is Radix Berberidis extracting solution.Merge aforesaid liquid, obtain combination medicine.
The preparation of embodiment 2 pharmaceutical composition of the present invention
Get Herba Portulacae 100g, Radix Berberidis 50g.Herba Portulacae decocts with water secondary, 2 hours first times, second time 1 hour, collecting decoction, and filter, filtrate is concentrated into clear paste, for subsequent use; Radix Berberidis adds 50% alcohol reflux twice, each one hour, and merge and filter, filtrate is concentrated into clear paste, adds above-mentioned Herba Portulacae clear paste, obtains clear paste A.Clear paste A is added appropriate dextrin, starch, prepares granule.
The preparation of embodiment 3 pharmaceutical composition of the present invention
(1) 10% aqueous acetic acid: 5ml acetic acid adds in 45ml distilled water, for subsequent use; 10% aqueous sodium carbonate: 5g sodium carbonate is dissolved in 45ml distilled water, for subsequent use; 30% formalin: 15ml formaldehyde adds in 35ml distilled water, for subsequent use.
(2) Herba Portulacae 100g is got, Radix Berberidis 50g.Herba Portulacae decocts with water secondary, 2 hours first times, second time 1 hour, collecting decoction, and filter, filtrate is concentrated into the clear paste that relative density is 1.35, for subsequent use; Radix Berberidis adds 50% alcohol reflux twice, each one hour, and merge and filter, filtrate is concentrated into the clear paste that relative density is 1.35, adds above-mentioned Herba Portulacae clear paste, obtains clear paste A.
(3) gelatin and arabic gum is taken, respectively the solution being made into mass concentration about 5% soluble in water, 50 DEG C of constant temperature water baths.Clear paste A is accurately taken, arabic gum and gelatin in the ratio of material medicine ratio (mass ratio of gelatin and arabic gum and crude drug extract) 5:l.Add part 5% gelatin solution, mixing speed is 400r/min, keep temperature 40 DEG C, abundant mixing slowly introduces residue gelatin solution and gumwater afterwards, after continuing to stir 15min, adjusts PH4.1 with 10% aqueous acetic acid, continue to stir, when clear paste tunicle wraps up, add the distilled water of a times amount about 40 DEG C, continue to stir and stop heating.When temperature is reduced to below 25 DEG C, move to ice-water bath continue to stir.When about 8 DEG C, adjust about PH8.5 with 10% sodium carbonate, add 30% formaldehyde 1ml after continuing to stir 15min, then stir 30min, take out centrifugalize (3000r/min), be washed to weakly acidic pH, be loaded on surface plate, 55 DEG C of oven for drying, obtain microcapsule formulation.
The preparation of embodiment 4 pharmaceutical composition of the present invention
(1) 10% aqueous acetic acid: 5ml acetic acid adds in 45ml distilled water, for subsequent use, 10% aqueous sodium carbonate: 5g sodium carbonate is dissolved in 45ml distilled water, for subsequent use, 30% formalin: 15ml formaldehyde adds in 35ml distilled water, for subsequent use.
(2) Herba Portulacae 100g is got, Radix Berberidis 50g.Herba Portulacae decocts with water secondary, 2 hours first times, second time 1 hour, collecting decoction, and filter, filtrate is concentrated into the clear paste that relative density is 1.35, for subsequent use; Radix Berberidis adds 50% alcohol reflux twice, each one hour, and merge and filter, filtrate is concentrated into the clear paste that relative density is 1.35, adds above-mentioned Herba Portulacae clear paste, obtains clear paste A.
(3) gelatin and arabic gum is taken, respectively the solution being made into mass concentration about 10% soluble in water, 50 DEG C of constant temperature water baths.Clear paste A is accurately taken, arabic gum and gelatin in the ratio of material medicine ratio (mass ratio of gelatin and arabic gum and crude drug extract) 1:l.Add part 10% gelatin solution, mixing speed is 200r/min, keep temperature 45 C, abundant mixing slowly introduces residue gelatin solution and gumwater afterwards, after continuing to stir 15min, adjusts PH3.6 with 10% aqueous acetic acid, continue to stir, when clear paste tunicle wraps up, add the distilled water of a times amount about 45 DEG C, continue to stir and stop heating.When temperature is reduced to below 25 DEG C, move to ice-water bath continue to stir.When about 8 DEG C, adjust about PH8.5 with 10% sodium carbonate, add 30% formaldehyde 2ml after continuing to stir 15min, then stir 30min, take out centrifugalize (3000r/min), be washed to weakly acidic pH, be loaded on surface plate, 55 DEG C of oven for drying, obtain microcapsule formulation.
The preparation of embodiment 5 pharmaceutical composition of the present invention
(1) 10% aqueous acetic acid: 5ml acetic acid adds in 45ml distilled water, for subsequent use, 10% aqueous sodium carbonate: 5g sodium carbonate is dissolved in 45ml distilled water, for subsequent use, 30% formalin: 15ml formaldehyde adds in 35ml distilled water, for subsequent use.
(2) Herba Portulacae 100g is got, Radix Berberidis 50g.Herba Portulacae decocts with water secondary, 2 hours first times, second time 1 hour, collecting decoction, and filter, filtrate is concentrated into the clear paste that relative density is 1.35, for subsequent use; Radix Berberidis adds 50% alcohol reflux twice, each one hour, and merge and filter, filtrate is concentrated into the clear paste that relative density is 1.35, adds above-mentioned Herba Portulacae clear paste, obtains clear paste A.
(3) gelatin and arabic gum is taken, respectively the solution being made into mass concentration about 7.5% soluble in water, 50 DEG C of constant temperature water baths.Clear paste A is accurately taken, arabic gum and gelatin in the ratio of material medicine ratio (mass ratio of gelatin and arabic gum and crude drug extract) 3:l.Add part 7.5% gelatin solution, mixing speed is 200r/min, keep temperature 50 C, abundant mixing slowly introduces residue gelatin solution and gumwater afterwards, after continuing to stir 15min, adjusts PH4.0 with 10% aqueous acetic acid, continue to stir, when clear paste tunicle wraps up, add the distilled water of a times amount about 50 DEG C, continue to stir and stop heating.When temperature is reduced to below 25 DEG C, move to ice-water bath continue to stir.When about 8 DEG C, adjust about PH8.5 with 10% sodium carbonate, add 30% formaldehyde 2ml after continuing to stir 15min, then stir 30min, take out centrifugalize (3000r/min), be washed to weakly acidic pH, be loaded on surface plate, 55 DEG C of oven for drying, obtain microcapsule formulation.
Below by way of concrete test example, beneficial effect of the present invention is described.
The antibacterial activity of test example 1 combination medicine of the present invention
1.1 extracorporeal bacteria inhibitor test
Adopt escherichia coli reference cultures C83902(to buy in National Veterinary Culture Collection) and clinical separating Escherichia coli as bacterial strain, measure the In Vitro Bacteriostasis effect (each group is all by the extraction of embodiment 1 method) of Herba Portulacae extract, Radix Berberidis extracting solution, drug combination respectively.Result of the test shows, is followed successively by the inhibition zone size order of escherichia coli type strain and clinical separation strain: drug combination > Radix Berberidis > Herba Portulacae.
1.2 bacterial-infection resisting tests
Select 18-20g mice average packet, often organize 10, be about 5.5 × 10 with the escherichia coli liquid 0.1ml(bacteria containing amount of clinical separation
9individual/ml) lumbar injection inoculation, mice is often organized respectively by each group of Chinese medicine extraction liquid lumbar injection (Radix Berberidis extracting solution group, Herba Portulacae extract group, drug combination group after 1h, all prepare by embodiment 1 for each group), the pig that dosage is recommended with reference to Chinese veterinary pharmacopoeia two draws with the highest consumption conversion, observes morbidity and the death condition of mice.The results are shown in Table 1.
Table 1 Traditional Chinese Medicine Anti bacteriological infection is tested
Result shows, Radix Berberidis, Herba Portulacae, drug combination all have control action to a certain degree, wherein drug combination best results to coli-infection mice.
The clinical trial of test example 2 pharmaceutical composition of the present invention
Test method
Gather the sick pig of experiment pig farm, the ground such as Wenjiang, Sichuan, Jianyang natural occurrence, the sick pig totally 100 of HUANGBAI(sic) dysentery is diagnosed as through epidemiology, clinical symptoms, test in laboratory, be divided into 2 groups at random, often organize 50, i.e. microcapsule formulation (prepared by embodiment 3) treatment group and plain particles (prepared by embodiment 2) matched group.Microcapsule formulation treatment group presses 0.2mL/kg dosage administered intramuscular for three days on end, the mixed drink of each 5-10g/ head of plain particles matched group, every day 2 times.Observe and add up the mortality rate, the mental status, clinical symptoms etc. that 3 days respectively organize laboratory animal.
Index of assessment of curative effect
Cure: the HUANGBAI(sic) dysentery transference cure of clinical appearance, perianal, without dirt, observes 3 days nothings phenomenon repeatedly.
Effective: the HUANGBAI(sic) dysentery symptom of clinical appearance obtains partial rcsponse, feces becomes dry, without the phenomena of mortality.
Invalid: the HUANGBAI(sic) dysentery symptom of clinical appearance is not improved, and occurs the piglet phenomena of mortality.
Table 2 clinical test results
Shown by clinical trial, the cure rate of microcapsule formulation of the present invention to pig HUANGBAI(sic) dysentery is high, is obviously better than plain particles agent.
In sum, the present invention is by after Radix Berberidis and Herba Portulacae conbined usage, and its Chinese People's Anti-Japanese Military and Political College enterobacteria is obviously better than the unit medicament under Isodose with the effect for the treatment of yellow and white dysentery of piglet, played synergistic function, provides a kind of new veterinary drug and selects.Meanwhile, medicine is prepared into microcapsule formulation by the present invention, masks the bitterness of Radix Berberidis, improves compliance and the stability of medicine, reaches the effect of slow release or controlled release, and makes liquid drug solid state be convenient to application and storage.
Claims (5)
1. treat a pharmaceutical composition for yellow and white dysentery of piglet, it is characterized in that: it is the microcapsule be prepared from by the supplementary material of following weight proportion:
Supplementary material proportioning is as follows:
The capsule heart and capsule material mass ratio are 1:(1 ~ 5);
Wherein, the capsule heart is water or the extractive with organic solvent of Radix Berberidis and Herba Portulacae; Capsule material is one or more the combination in gelatin, arabic gum, alginate, chitosan, carboxymethyl cellulose salt, ethyl cellulose, methylcellulose, hypromellose;
The preparation method of described extract is as follows: get Radix Berberidis: Herba Portulacae=(1 ~ 3): (1 ~ 3) w/w, and Herba Portulacae decocts with water, collecting decoction, and filter, filtrate is concentrated into the clear paste that relative density is 1.35, for subsequent use; Radix Berberidis adds 50%v/v ethanol extraction, and merge extractive liquid, filters, and filtrate is concentrated into the clear paste that relative density is 1.35, adds above-mentioned Herba Portulacae clear paste, obtains crude drug extract;
The preparation method of microcapsule is as follows:
(1) gelatin and arabic gum is taken, respectively the solution being made into mass concentration 5 ~ 10% soluble in water, 40 ~ 60 DEG C of constant temperature water baths; Weighting raw materials extract, fully mixes with part of gelatin solution, then with gumwater with remain gelatin solution and mix homogeneously;
(2) keep temperature to be 40 ~ 60 DEG C, adjust pH to 3.6 ~ 4.5 with aqueous acetic acid, continue to stir, when crude drug extract tunicle wraps up, add water, continue to stir and stop heating, when temperature is reduced to below 25 DEG C, move to ice-water bath continue to stir, then adjust pH to 8 ~ 9 with sodium carbonate, continue to stir, add cross-linking agent again, crosslinking curing, centrifugalize, solid content is washed to weakly acidic pH, drying, to obtain final product.
2. pharmaceutical composition according to claim 1, is characterized in that: Radix Berberidis: Herba Portulacae=1:2.
3. pharmaceutical composition according to claim 1, is characterized in that: described capsule material is gelatin: arabic gum=(1 ~ 3): (1 ~ 3) w/w.
4. the preparation method of microcapsule described in claim 1, is characterized in that: it comprises following operating procedure:
(1) gelatin and arabic gum is taken, respectively the solution being made into mass concentration 5 ~ 10% soluble in water, 40 ~ 60 DEG C of constant temperature water baths; Weighting raw materials extract, fully mixes with part of gelatin solution, then with gumwater with remain gelatin solution and mix homogeneously;
(2) keep temperature to be 40 ~ 60 DEG C, adjust pH to 3.6 ~ 4.5 with aqueous acetic acid, continue to stir, when crude drug extract tunicle wraps up, add water, continue to stir and stop heating, when temperature is reduced to below 25 DEG C, move to ice-water bath continue to stir, then adjust pH to 8 ~ 9 with sodium carbonate, continue to stir, add cross-linking agent again, crosslinking curing, centrifugalize, solid content is washed to weakly acidic pH, drying, to obtain final product.
5. preparation method according to claim 4, is characterized in that: described cross-linking agent is formaldehyde.
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| CN104435046B (en) * | 2014-12-17 | 2017-11-24 | 成都乾坤动物药业有限公司 | A kind of fermentation medicine for treating piglet yellow-white dysentery and preparation method thereof |
| CN105106269A (en) * | 2015-09-17 | 2015-12-02 | 成都乾坤动物药业有限公司 | Traditional Chinese veterinary medicine for treating livestock and poultry bacterial diarrhea, preparation method and application thereof |
| CN105582037A (en) * | 2016-01-27 | 2016-05-18 | 成都乾坤动物药业有限公司 | Medicine composition for treating bacterial diseases of poultry |
| CN105726602A (en) * | 2016-02-02 | 2016-07-06 | 广东容大生物股份有限公司 | Sanma granules and preparation method and processing system thereof |
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Address after: 611130 Wenjiang, Chengdu, Chengdu cross strait science and Technology Industrial Development Zone, Jin Fu Road, Sichuan Patentee after: Chengdu Qiankun animal pharmaceutical Limited by Share Ltd Address before: 611130 Wenjiang, Chengdu, Chengdu cross strait science and Technology Industrial Development Zone, Jin Fu Road, Sichuan Patentee before: Chengdu Qiankun Animal Pharmaceutical Co.,Ltd. |
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