CN1370575A - Composite prepn for preventing and treating young animal's darrhea and its prepn process - Google Patents
Composite prepn for preventing and treating young animal's darrhea and its prepn process Download PDFInfo
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- CN1370575A CN1370575A CN 02100132 CN02100132A CN1370575A CN 1370575 A CN1370575 A CN 1370575A CN 02100132 CN02100132 CN 02100132 CN 02100132 A CN02100132 A CN 02100132A CN 1370575 A CN1370575 A CN 1370575A
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The present invention is composite preparation for preventing and treating young animal's diarrhea. Multiple polyvalent antibody, antibody protecting synergist, fructose, mannose, yeast polysaccharide and dry medicine power prepared with phellodendron bark, biota leaf, goldthread root and other seven kinds of Chinese medicinal materials as well as deionized water are mixed, emulsified, filtered, centrifugally spray-dried and sieved to obtain the composite preparation product. The persent invention combines immunological prevention and cure, medicinal prevention and cure and microecological prevention and cure into one integral and the preparation has high effect.
Description
Technical field
The invention belongs to veterinary medicine, a kind of control young stock diarrheal antibody Chinese medicine bifidus factor compound formulation and preparation method thereof of more specifically saying so.
Background technology
Control young stock diarrhoea mainly contains three kinds of methods at present:
1. pregnant female immune protection method
Pregnant female just before giving birth before 30-40 days, 15-20 days inject respectively and to cause multiple vaccine of young stock diarrheal and vaccine, young stock fed rapidly and inhaled colostrum acquisition maternal antibody puerperal, maternal antibody directly enters in blood and the body fluid by the gastrointestinal tract of newborn young stock, thereby reaches control young stock diarrheal purpose.But this method causes that easily pregnant female produces stress, causes depressed, the loss of appetite of spirit, and then causes untoward reaction such as weak tire, miscarriage, premature labor, nascent weight loss and puerperal hypogalactia, has influence on young stock diarrheal integrated control effect.
2. young stock diarrhoea female animal prevents method of treatment
Give female animal dispensing in puerperal, as Rhizoma Atractylodis fragrant connect loose, medicine such as female young spirit, by milk the medicine active ingredient is passed to young stock, reach control young stock diarrheal purpose.But because the Chinese powder medicine effective component content is low, dosage is big, and young stock inhales breast and measures reasons such as inhomogeneous, and prevention effect is not ideal enough.
Above-mentioned two kinds of methods all are subjected to the influence of female animal body condition, particularly the female animal hypogalactia time, these methods all without any prevention effect.
3. the direct dose regimen of young stock
(1) give young stock directly for oral administration or injection of antibiotics and chemical synthetic drug,, norfloxacin diffusing, ciprofloxacin, enrofloxacin, furazolidone etc. as gentamycin, streptomycin, penicillin, chloromycetin, kanamycin, erythromycin, cephalosporin, oxytetracycline, neomycin, connection sulphur.But owing to use these medicines repeatedly in large quantities for many years, produced drug resistance in various degree, its prevention effect is not ideal enough, as common antibiotic to the colibacillary responsive rate between 15-70%; Moreover human drugs and veterinary drug intersect use, the residual increase of medicine in the livestock products, the mankind have eaten the food of these high residue medicines, bring out people's Drug resistance, brought great difficulty for human resist the disease, treatment disease, therefore all progressively limit in the world wide at present and forbid in livestock and poultry breeding industry, using antibiotic and chemical synthetic drug.
(2) to young stock various Chinese powder medicines for oral administration, as the HUANGBAI(sic) dysentery relieving loose, Fructus Mume looses, the fragrant company of Rhizoma Atractylodis looses, the Radix Pulsatillae looses etc.Because this class powder forms by the direct grinding and processing of former medicine, consumption is big, drug effect is low, use reason such as inconvenience, and it is also bad therefore to prevent and treat young stock diarrheal effect.
(3) for oral administration or injection height is exempted from chicken yolk antibody and is reached control young stock diarrheal purpose to young stock.This law is effective, does not produce drug resistance, no drug residue and toxic and side effects, but all at the experimental stage at present, do not form stable formulation, can not produce in bulk.People's " development and application of the anti-Radix Polygalae Crotalarioidis Escherichia of chicken yolk antibody " such as Xiao Chi (Chinese veterinary's science and technology, 1998 years, the 28th volume, the 4th phase) for example; Lee state equality people " the swine escherichia coli height is exempted from the development of chicken yolk antibody " (Fujian animal and veterinary, 1998 the 2nd phases).
Aspect production Technology, also have the extraction process of yellow antibody, common having " utilizes the research of phenol purification yolk antibody from yolk " (Chinese veterinary's science and technology, 1998 the 28th volumes, the 10th phase); " Polyethylene Glycol extracts the research " (1989 the 2nd phases of Chinese poultry infectious disease, total 45 phases of phase) of yolk IgG; " " water extraction ", " PEG extraction method " etc. (Jqurnal of ImmuologuicalMethods 160 (1993) 207-214).Said method yields poorly, and is difficult to form industrialized mass production.
Summary of the invention
The objective of the invention is to overcome the shortcoming of prior art, propose a kind of pure natural, no drug residue, green veterinary medicine one pollution-free, that have no drug resistance, have no side effect and be used to prevent and treat two qi factor compound formulations of young stock diarrheal antibody Chinese medicine and preparation method thereof.
Main technical principle of the present invention and scheme: on the basis that modern molecular immunology and Chinese medicine combine, adopt modern biotechnology, from high immune egg, extract the multi-joint multivalent antibody of anti-young stock diarrheal, then it mixed with plurality of Chinese active ingredient, two qi factor, spray drying, sieve etc., make required product.
Compound formulation composition of the present invention and content (in parts by weight) thereof:
Multi-joint multivalent antibody 2-15 part; Antibody synergistic protector 5-25 part; Be selected from one or more the two qi factor saccharides in fruit oligose, manna oligosaccharide, the zymosan, wherein fruit oligose 0.5-5 part, manna oligosaccharide 0.5-5 part, zymosan 0.5-5 part; And the dry powder more than five kinds in the following Chinese medicine dry powder after the decocting spray drying: Cortex Phellodendri 0.5-10 part, Cacumen Platycladi 0.5-10 part, Rhizoma Coptidis 0.5-15 part, Cortex Fraxini 0.5-8 part, Radix Pulsatillae 0.5-8 part, Rhizoma Atractylodis 0.5-10 part, Radix Aucklandiae 0.5-10 part, Radix Sophorae Flavescentis 0.5-10 part, Herba Plantaginis 0.5-5 part, Rhizoma Alismatis 0.5-5 part.
The preparation method of compound formulation of the present invention comprises following process:
(1) produces the high immune egg of multi-joint multivalence
A. no-special pathogen laying hen (SPF chicken) is in the isolated rearing of clean plant;
B. begin to lay eggs the first two months to the laying hen initial immunity, its method: every chicken is injected following vaccine and vaccine respectively simultaneously; Salmonella multivalence bacterium, colibacillus multivalence bacterium, clostridieum welchii multivalence bacterium (perhaps rabbit pestilence-pasteurellosis bacillus-clostridieum welchii three inactivated bacteria or sheep braxy-lamb dysentery-struck-intestinal toxenia-black disease 5-linked Seedling), transmissible gastroenteritis vaccine, rotavirus diarrhoea Seedling, an injection volume 0.5ml/ chicken of every kind of vaccine and vaccine;
C. two week backs are to laying hen immunity for the second time, and its method: every chicken is injected following vaccine respectively: escherichia coli multivalence Seedling and pseudorabies inactivated vaccine, an injection volume 0.5ml/ chicken of every kind of vaccine and vaccine;
D. the back is to laying hen immunity for the third time around, and its method: every chicken is injected following vaccine respectively: transmissible gastroenteritis vaccine, epidemic diarrhea vaccine, rotavirus diarrhoea Seedling, 0.5ml/ chicken of every kind of vaccine injection amount;
E. six all backs are to the 4th immunity of laying hen, its method: every chicken is injected following vaccine and vaccine respectively: Salmonella multivalence Seedling, colibacillus multivalence bacterium, clostridieum welchii multivalence bacterium (or rabbit pestilence-pasteurellosis bacillus-clostridieum welchii three inactivated bacteria or sheep braxy-lamb dysentery-struck-intestinal toxenia-black disease 5-linked Seedling), transmissible gastroenteritis vaccine, pseudorabies inactivated bacteria, rotavirus diarrhea Seedling, and the injection volume of every kind of vaccine and vaccine is a 0.5ml-1.0/ chicken;
F. carrying out the yolk antibody immunology detection after eight weeks is K88, K99 in the multi-joint multivalent antibody, 987P antibody agglutination titer up to standard 1: 160-1: the high immune egg of multi-joint multivalence is collected in 640 backs, under 16 ℃ of conditions, preserve stand-by, if detect defective, repeating step (e), again immunity, qualified until detecting;
(2) multi-joint multivalent antibody is purified
A. the high immune egg of multi-joint multivalence that step (1) is obtained is sterilized earlier, smashes egg again and separates, and obtains egg white and yolk, and wherein egg white is spray-dried, makes the egg white powder;
B. 2-10 sterile deionized water and the 0.1-1.0NHCl doubly that in (a) step yolk, adds yolk weight, make pH value to 5.0-5.8, add NaCl, concentration is to 0.5-0.9% (W/W), add Polyethylene Glycol-6000 (PEG-6000) again, concentration stirs then after 10-20 minute and left standstill 0.5-24 hour, when the controlling liquid temperature is 4-20 ℃ to 3.5-5.0% (W/V), descended centrifugal 10-30 minute at 3000-15000 rev/min, obtain supernatant and precipitate, precipitate is spray-dried, obtains powdery yolk;
C. in (b) supernatant in step, add PEG-6000, concentration is to 12-15% (W/V), add 0.1-1.0N NaOH again, make pH value to 6.8-7.5, stirred 10-20 minute, left standstill 0.5-24 hour, when liquid reaches 4 ℃, descended centrifugal 20-40 minute at 3000-15000 rev/min, abandoning supernatant, precipitate is multi-joint multivalent antibody semifinished product;
D. multi-joint multivalent antibody semifinished product is dissolved in the sterile deionized water, repeat (c) step process again, get precipitation, carry out that antibody titer is determined as K88, K99,987P antibody agglutination titer reaches 1: 320 ∽ and promptly obtains purified multi-joint multivalent antibody at 1: 2560, the amount of described sterile deionized water be multi-joint multivalent antibody semifinished product weight 2-10 doubly;
(3) produce Chinese medicine dry powder
The Chinese herbal medicine more than five kinds or five kinds that is selected from Cortex Phellodendri, Cacumen Platycladi, Rhizoma Coptidis, Cortex Fraxini, the Radix Pulsatillae, Rhizoma Atractylodis, the Radix Aucklandiae, Radix Sophorae Flavescentis, Herba Plantaginis, the Rhizoma Alismatis extracts by following process respectively, makes dry powder:
A. cold water soak 1-5 hour used in raw material of Chinese medicine chopping, clean back, fully soak into the 5-8 water doubly that the back adds raw material weight to the medicine heart, be heated to boiling back slow fire boiling, decocted 30-60 minute for the first time, pour out medicinal liquid, and then carry out twice decoction, decoct amount of water is 5 times of water of raw material weight at every turn, decocts 1-2 hour, then three medicinal liquids are mixed and obtain admixing medical solutions, add 3 times of water of raw material weight in the remaining medicinal residues again, decocted 30 minutes, medicinal liquid is used for the next group medicine and decocts use;
B. will go on foot poly-(a) admixing medical solutions, at negative pressure 3-8 kPa, temperature 40-80 ℃ following concentrating under reduced pressure, to the water content of dry be 10-15%, the centrifugal again soil of removing;
C. the material removed behind the soil of step (b) carries out spray drying on drying machine with centrifugal spray, promptly obtains Chinese medicine dry powder, described spray dryer operating condition: inlet temperature 150-280 ℃, outlet temperature 70-90 ℃, rotating speed 12000-30000 rev/min;
(4) produce the two qi factor compound formulations of antibody Chinese medicine
The purified multi-joint multivalent antibody that step (2) is made; the antibody synergistic protector; step (3) is made the Chinese medicine dry powder of carrying respectively and is comprised fruit oligose; manna oligosaccharide; zymosan at interior two qi factor saccharides behind mixing; add sterile deionized water; weight concentration to mixture reaches 25-30%; emulsifying on high-speed emulsifying machine or homogenizer then; filter; after spray drying on the drying machine with centrifugal spray, cross 3-5 number sieve then; carry out quality examination at last; packing; warehouse-in, described spray dryer operating condition: inlet temperature 150-220 ℃; outlet temperature 65-90 ℃; rotating speed 12000-30000 rev/min; negative pressure 10-80 handkerchief.
The multi-joint multivalent antibody K88 of described product, K99,987P antibody agglutination titer reach more than 1: 320, the berberine thin layer chromatography is checked positive, assorted bacterium sum≤1000/gram, pathogenic bacterium and escherichia coli feminine gender, yeast and fungi count≤100/gram, water content≤8%;
Other composition fruit oligose of the present invention, manna oligosaccharide, zymosan and all Chinese herbal medicine all are the commercially available prod, and described antibody synergistic protector comprises following three kinds, and their prescription is: (1) meso ring ethanol 5%, strong horse serum 95%; (2) bovine serum albumin 10 gram, sodium glutamate 0.83 gram, potassium dihydrogen phosphate 0.52 gram, sodium hydrogen phosphate 1.64 grams, sucrose 76.62 grams, sterile deionized water are 1000 milliliters; (3) polyvinylpyrrolidone K30-351 gram, lactose 10 grams, 100 milliliters of (Wang Mingjun etc. of sterile deionized water, " veterinary biological product ", Chinese agriculture publishing house, front page in 1997, the 345th page and Xing Zhao etc., " veterinary's goods biology practical technique ", Chinese agriculture publishing house, the 1st edition the 125th page of July in 2000).
Used spray dryer, high-speed emulsifying machine or the homogenizer of preparation process of the present invention all is known common equipment.
K88 of the present invention, K99,987P antibody titer assay method are referring to " development of the anti-Radix Polygalae Crotalarioidis bacterium of chicken yolk antibody " (Chinese poultry infectious disease, 1994 the 2nd phases, 26-27 page or leaf) of beard letter etc.; Described berberine thin layer chromatography discrimination method is seen " People's Republic of China's veterinary drug allusion quotation, version in 2000,25 pages of appendix ".
Main advantage of the present invention and effect:
1. compound formulation of the present invention is with existing immune protection, medical treatment and microecology control, and set overcomes the three and uses multiple shortcoming and the drawback of bringing respectively for one effectively.For example to farrowing sow injection escherichia coli trivalent Seedling, control yellow and white dysentery of piglet; Injection clostridieum welchii multivalence Seedling, the control piglet red dysentery is given conceived cow and ewe injection escherichia coli, control calf and lamb escherichia coli dysentery or the like.And compound formulation of the present invention contains anti-Escherichia coli multivalent antibody, anti-clostridieum welchii multivalent antibody, anti-rotavirus diarrhoea multivalent antibody, anti-Pseudorabies virus antibody, anti-Salmonella multivalent antibody, infectivity resistant gastrointestinal antibody-like, anti-epidemic diarrhea antibody etc., formed multi-joint multivalent antibody, directly gavage to young stock, all stress that the active immunity female animal brings to female animal have not only been broken away from, and then have influence on embryo and young stock, and can accurately directly give young stock with various control diarrheal antibody, this passive immunity, the most definite, prevented and treated young stock diarrhoea most effectively;
Compound formulation young stock of the present invention is directly taken, the active ingredient of purified Chinese medicine anti-infective can be sent into carcass, overcome the drug resistance and the residual shortcoming of high medicine of antibiotic and chemical synthetic drug, also overcome the shortcoming that existing Chinese powder medicine consumption is big, drug effect is low, use is inconvenient; Young stock is directly taken compound formulation of the present invention and the various pairs of qi factors can be sent into carcass in addition, cultivate beneficial bacterias such as young stock intestinal bifidus bacillus and lactobacillus effectively, set up good microecosystem, suppress and kill various pathogens in the young stock intestinal, prevented and treated young stock diarrhoea effectively.
2. the antibody synergistic protector of compound formulation of the present invention, effective components of Chinese medicinal and two qi factor; multi-joint multivalent antibody is had excellent protection and increases the effect of tiring; unstability when having overcome high immunity yolk antibody processing, storage, transportation and use etc. under the condition and cause the inefficacy disadvantage of antibody, formed stable a kind of in Types of Medicine antibody biological preparation.
3. the production Technology among the present invention, antagonist purification aspect transfer pH value to 5.0-5.8 with 0.1-1.0N HCl in defat, and add NaCl and make the concentration of NaCl in the high-immunity yolk water liquid liquid reach 0.5-0.9%; On the antibody precipitation, transfer PH to 6.8-7.5, make the purification response rate of antibody increase more than 1 times with 0.1-1.0N NaOH.On the finished product synthesis technique, during the high speed centrifugation spraying, control 150-220 ℃ of inlet temperature in addition, outlet temperature 65-90 ℃, 12000-30000 rev/min of shower nozzle rotating speed, negative pressure 15-80 handkerchief are important leverage conditions of the present invention.
4. the compound formulation among the present invention is aspect prevention, after every newborn young stock birth, gavages the 0.5-1.0 gram before the suckling immediately, popular district young stock, weak son, entrusts one's child to the care of sb. young every and gavages 1.0-2.0 and restrain, and can prevent newborn young stock that diarrhea disease did not take place in 7-21 days; In opening tonic feed material or feed for weaned, add this preparation 0.2-0.5%, can prevent supplementary feeding young stock and weanling that diarrhea disease takes place, aspect treatment, make every each clothes 2 grams of young stock 1-2 week, make every each clothes 2-4 gram of young stock 3-4 week, 5 weeks, above 4-8 restrained, every day two to three times, three is a course of treatment, but uniform mixing is fed in feedstuff, or gavage with an amount of dilution of normal saline or cold water, according to the state of an illness increase and decrease dosage of following the doctor's advice.Gavage immediately after the dilution of this preparation, be sure not the high temperature heating and use, and preserve at airtight, dry place, storage life is 12-18 month.
Use the present invention to listen compound formulation, than common pregnant female immune protection method, anti-method of treatment of young stock diarrhoea female animal and the direct dose regimen of young stock improve young stock survival rate 10-30%, and the young stock survival rate is reached more than 95%, shorten young stock 21-28 age of sucking days, increase about weanling body weight 8-25%, diarrhoea young stock cure rate is more than 90%, and pregnant female exempts to beat the various vaccines of control young stock diarrheal, reduces the work workload, reduce production costs, improve overall economic efficiency.
In sum, antibody Chinese medicine bifidus factor compound formulation of the present invention is on the theoretical basis that modern molecular immunology and Chinese medicine combine, adopt modern ovary bioreactor engineering and high-new physics and chemistry process technology, refining a kind of pure natural, the no drug residue, pollution-free that immune protection, medical treatment and microecology are prevented and treated, the novel green veterinary drug that has no drug resistance, has no side effect of integrating that forms.
Description of drawings
Fig. 1 exempts from egg technological process of production figure for the pig multi-associated multivalence antibody height;
Fig. 2 is Rhizoma Coptidis, Cortex Phellodendri, Cortex Fraxini Chinese herbal medicine extracting process chart;
Fig. 3 is the Radix Pulsatillae, Cacumen Platycladi Chinese herbal medicine extracting technology;
Fig. 4 exempts from egg production technology flow chart for rabbit with multi-joint multivalence height;
Fig. 5 exempts from egg production technology flow process journey figure for sheep with multi-joint multivalence height.
The specific embodiment
Further specify characteristics of the present invention below by specific embodiment.
Example 1
This example is that the preparation pig is used the two qi factor compound formulations of antibody Chinese medicine.
(1) the compound formulation prescription of this example:
6.5 kilograms of pig multi-associated multivalence antibodys
15.0 kilograms of antibody synergistic protectors
0.5 kilogram of fruit oligose
1.5 kilograms of Cortex Phellodendris
1.5 kilograms of Cacumen Platycladis
2.0 kilograms of Rhizoma Coptidis
0.5 kilogram of Cortex Fraxini
0.5 kilogram of the Radix Pulsatillae
Above-mentioned all Chinese herbal medicine weight are decocting extraction, spray drying thing weight.
Described antibody synergistic protector prescription (weight): meso ring ethanol 5%, strong horse serum 95%.
(2) preparation process is as follows:
1. produce the pig multi-associated multivalence antibody height by Fig. 1 flow process and exempt from egg;
2. pig multi-associated multivalence antibody purifying technique
(1) pig is exempted from egg with multi-joint valency antibody height, detoxicating, beats eggs, separates, and pure egg white spray drying gets the egg white powder;
(2) multi-joint multivalent antibody high-immunity yolk adds 4 times of sterile deionized water, adds 0.1-1.0N HCl, pH value to 5.0, add NaCl, concentration to 0.5% (W/W), add PEG-6000, concentration to 3.5% (W/V), stir 10 minutes, leave standstill 10 ℃ of 30 minutes, temperature of liquid, 14000 rev/mins, after centrifugal 10 minutes, abandon precipitation, spray drying is carried powdery yolk;
(3) add PEG-6000 in the supernatant, ultimate density to 12% (W/V) adds 0.1-1.0N NaOH, pH value to 7.2, stir 10 minutes, left standstill 8 hours, when temperature of liquid reaches 4 ℃, at 14000 rev/mins, after centrifugal 25 minutes, abandoning supernatant, precipitation is multi-joint multivalent antibody semifinished product;
(4) add sterile deionized water, repeating step (3) at multi-joint multivalent antibody semifinished product and get precipitation to carry out the antibody titer test fixed, K88, K99,987P antibody titer all reach 1: 1280, promptly obtain refining pig with getting multivalent antibody more;
3. the Chinese medicine decocting extracts drying process with atomizing
A. press Fig. 2 flow process to Rhizoma Coptidis, Cortex Phellodendri, the extraction of Cortex Fraxini Chinese herbal medicine decocting, spray drying;
B. press Fig. 3 flow process to the Radix Pulsatillae, the extraction of Cacumen Platycladi Chinese herbal medicine decocting, spray drying;
4. pig is used antibody Chinese medicine bifidus factor compound formulation finished product synthesis and production process
Formula material is mixed, add sterile deionized water, make dry substance concentration reach 28%; → in high-speed emulsifying machine, 4000 rev/mins; → emulsify at a high speed 20 minutes; → filter by No. 4 sieves; → at Highspeedcentrifugingandsprayingdrier (inlet temperature 165-170 ℃, outlet temperature 70-75 ℃, 13200 rev/mins of fog-spray nozzle rotating speeds, negative pressure 20 handkerchiefs); → spray drying → outlet material temperature≤65 ℃ → cross sieve → carry out that quality examination → 1. the K88K99987P antibody titer reaches 1: 320 for No. 4; 2. the berberine thin layer chromatography is checked positive; 3. assorted bacterium sum≤1000/gram; 4. pathogenic bacterium and escherichia coli feminine gender; 5. yeast and fungi count≤100/gram; 6. water content≤8%; → packing → decals → packing → finished product → warehouse-in.
(3). pig is used the antibody Chinese medicine bifidus factor result of use of back preparation again
1. act on and purposes
The special inhibition of this preparation and kill pig Escherichia coli, clostridieum welchii, baby swine paratyphoid Salmonella and and diarrhea inducing rotavirus, transmissible gastro-enteritis virus, epidemic diarrhea virus and Pseudorabies virus, simultaneously other pathogenic microbes is also had and suppress and killing action, excite piglet autoimmune system, prolong immunization, improve immunity, promote the growth of beneficial bacteria of intestinal tract propagation stomach function regulating intestinal mucosa cells.Multiple infectious diarrheas such as specially good effect control yellow and white dysentery of piglet, red diarrhea, green dysentery, watery dysentery.
2. usage and consumption
The prevention aspect, every neonatal pig piglet 0.5 gram, disease popularity district piglet, weak son, entrust one's child to the care of sb. young every 1.0 gram, every gram dilutes with 6-8 ml physiological saline or cold water, shake up, gavage immediately before the piglet birth back milk or in opening tonic fear feedstuff and ablactational baby pig feedstuff, add these goods 0.2-0.5%, prefabricated suckling pig and ablactational baby pig pathogenicity diarrhoea.
The treatment aspect makes every each 2 grams of piglet 1-2 week, makes every each 2-4 gram of piglet 3-4 week, every each 4-8 gram of wean back piglet, every day two to three times, three is a course of treatment, but uniform mixing is fed in beverage, or gavages with normal saline or cold water dilution.
Be sure not the high temperature heating and use, gavage immediately after the dilution, airtight, cool dark dry place preserves 18 months effect duration.
3. prevention effect
A. use this preparation prevention newborn piglet diarrhoea to improve survival rate 10-20% than other common method, promptly every nest pig connects 10 newborn piglets and calculates, and can survive the 1-2 head more, increases benefit at least to more than the 80-160 unit.See following table for details:
| Group | Usage and consumption | A test number | Sickness rate | Mortality rate | Survival rate | Survival rate improves, % | ||
| Than immunity | Compare antibiotic | Than blank | ||||||
| This preparation | Obey 0.5 gram immediately after every newborn piglet birth | ????1294 | ??9.3％ | ??3.2％ | ????96.8％ | ????9.6 | ????12.7 | ????26.1 |
| Big bar Enterobacter cloaca trivalent Seedling (K88, K99,987P) red diarrhea AC Seedling, transmissible gastroenteritis one epidemic diarrhea bigeminy Seedling | Farrowing sow each immunity in antenatal 40,20 days once, a 2ml | ????606 | ??39.1％ | ??12.8％ | ????87.2％ | ????2.5 | ????17.0 | |
| Big or the norfloxacin (injection) of celebrating | Take 2-3ml immediately after every newborn piglet birth | ????236 | ??34.3％ | ??15.3％ | ????84.7 | ????14.5 | ||
| Blank | ????429 | ??71.3％ | ??29.8％ | ????70.2％ | ||||
B, use this preparation for treating porkling diarrhoea than more than other method commonly used raising cure rate 10-20%.See following table for details:
| Group | A treatment number | Cure a number | Cure rate |
| This preparation | ????213 | ????208 | ??97.8％ * |
| Gentamycin | ????200 | ????156 | ??77.9％ |
| Furazolidone | ????301 | ????210 | ??69.8％ |
| Radix Pulsatillae powder | ????124 | ????105 | ??84.7％ |
*Compare with other 3 groups, difference is (P＜0.01) extremely significantly
Example 2
This example is that rabbit is used the two qi factor compound formulations of antibody Chinese medicine
1. fill a prescription:
2 kilograms of Herba Chenopodii Aristati extracts
5 kilograms of antibody synergistic protectors (with example 1)
0.5 kilogram of manna oligosaccharide
1.0 kilograms of zymosans
0.5 kilogram of Cortex Phellodendri
0.5 kilogram of Cacumen Platycladi
0.5 kilogram of Rhizoma Coptidis
0.5 kilogram of Cortex Fraxini
0.5 kilogram of Rhizoma Atractylodis
0.5 kilogram of Radix Sophorae Flavescentis
0.5 kilogram of Rhizoma Alismatis
Above-mentioned all Chinese herbal medicine weight are decocting extraction, spray drying thing weight.
2. production technology
(1) produces rabbit by Fig. 4 technological process and exempt from egg with multi-joint multivalence height
(2) rabbit is with multi-joint valency antibody purifying technique
With example 1 pig multi-associated multivalence antibody purifying technique.
(3) the Chinese medicine decocting extracts drying process with atomizing
Extract drying process with atomizing with example 1 pig with the Chinese medicine decocting, wherein Radix Sophorae Flavescentis, Rhizoma Alismatis technology are with Fig. 2 technological process, and Rhizoma Atractylodis technology is with Fig. 3 technological process.
(4) rabbit is used the two qi factor compound formulation synthesis techniques of antibody Chinese medicine
Use technology with example 1 pig.
3. act on and purposes
Multiple infectious diarrheas such as specially good effect control rabbit colibacillosis, clostridieum welchii disease, rotaviral enteritis.
4. usage and consumption
Per kilogram of body weight 0.4-0.6 gram, every day two to three times, three is a course of treatment, gavages with normal saline or an amount of dilution of cold water.
Prevention is used, and per hundred kilograms of feedstuffs add 200-500 and restrain this preparation.
5. result of use
This preparation improves 9.1% than the plain antibiotic therapy group of blue or green chain thunder cure rate, improves more than 30% than Radix Pulsatillae decocted medicine treatment group cure rate.See following table for details:
| The medicine group | The morbidity number of elements | Cure number of elements | Cure rate |
| This preparation | ????115 | ????110 | ??96.0％ * |
| Penicillin+streptomycin | ????99 | ????86 | ??86.9％ |
| Radix Pulsatillae powder | ????24 | ????15 | ??60.5％ |
*This preparation cure rate is than the extremely remarkable P of other two groups of effects＜0.01.
Example 3
This example is that sheep is used the two qi factor compound formulations of antibody Chinese medicine.
15 kilograms of sheep multi-associated multivalence antibody
25 kilograms of antibody synergistic protectors
5 kilograms of manna oligosaccharide
5 kilograms of fruit oligoses
10 kilograms of Cortex Phellodendris
10 kilograms of Cacumen Platycladis
15 kilograms of Rhizoma Coptidis
8 kilograms of Cortex Fraxinis
8 kilograms of the Radix Pulsatillaes
10 kilograms of the Radix Aucklandiae
5 kilograms of Herba Plantaginiss
Above-mentioned all Chinese herbal medicine weight are decocting extraction, spray drying thing weight.
Described antibody synergistic protector prescription: 100 milliliters of polyvinylpyrrolidone K30-351 grams, lactose 10 grams, sterile deionized water.
2. production technology
(1) produces sheep by Fig. 5 technological process and exempt from egg with multi-joint multivalence height
(2) sheep multi-associated multivalence antibody purifying technique
With example 1 pig multi-associated multivalence antibody purifying technique.
(3) the Chinese medicine decocting extracts drying process with atomizing
Extract drying process with atomizing with example 1 pig with the Chinese medicine decocting, wherein Radix Aucklandiae technology is with Fig. 2 technological process, and Herba Plantaginis technology is with Fig. 3 technological process.
(4) sheep is used the two qi factor compound formulation synthesis techniques of antibody Chinese medicine
Use technology with example 1 pig.
3. act on and purposes
Multiple infectious diarrheas such as specially good effect control sheep colibacillosis, clostridieum welchii disease, rotaviral enteritis.
4. usage and consumption
Per kilogram of body weight 0.5-0.8 gram, every day two to three times, three is a course of treatment, gavages with normal saline or an amount of dilution of cold water.
Prevention is used, and per hundred kilograms of feedstuffs add 200-500 and restrain this preparation.
5. result of use
Use this preparation for treating lamb pathogenicity diarrhoea to improve respectively about 10% and 20% than common antibiotics and Radix Pulsatillae decocted medicine treatment rate.See following table for details:
| The medicine group | The morbidity number of elements | Cure a number | Cure rate |
| This preparation | ????88 | ????84 | ????95.5％ * |
| Gentamycin+LIJUNJING | ????125 | ????105 | ????84.0％ |
| Radix Pulsatillae powder | ????32 | ????24 | ????75.5％ |
*This preparation cure rate is than the extremely remarkable P of other two groups of effects＜0.01.
Claims (2)
1 one kinds are used to prevent and treat young stock diarrheal compound formulation, it is characterized in that composition and parts by weight thereof:
Multi-joint multivalent antibody 2-15 part; antibody synergistic protector 5-25 part; be selected from one or more the two qi factor saccharides in fruit oligose 0.5-5 part, manna oligosaccharide 0.5-5 part, zymosan 0.5-5 part, and be selected from the dry powder more than five kinds in the following Chinese medicine dry powder after the decocting spray drying: Cortex Phellodendri 0.5-10 part, Cacumen Platycladi 0.5-10 part, Rhizoma Coptidis 0.5-15 part, Cortex Fraxini 0.5-8 part, Radix Pulsatillae 0.5-8 part, Rhizoma Atractylodis 0.5-10 part, Radix Aucklandiae 0.5-10 part, Radix Sophorae Flavescentis 0.5-10 part, Herba Plantaginis 0.5-5 part, Rhizoma Alismatis 0.5-5 part.
The preparation method of the described compound formulation of 2 claim 1 may further comprise the steps:
(1) produces the high immune egg of multi-joint multivalence
A. the no-special pathogen laying hen is in the isolated rearing of clean plant;
B. begin to lay eggs the first two months to the laying hen initial immunity, its method: every chicken is injected following vaccine and vaccine respectively simultaneously, Salmonella multivalence bacterium, colibacillus multivalence bacterium, clostridieum welchii multivalence bacterium or rabbit pestilence-pasteurellosis bacillus-clostridieum welchii three inactivated bacteria, sheep braxy-lamb dysentery-struck-intestinal toxenia-black disease 5-linked Seedling, the transmissible gastroenteritis vaccine, rotavirus diarrhoea Seedling, an injection volume 0.5ml/ chicken of every kind of vaccine and vaccine;
C. two week backs are to laying hen immunity for the second time, and its method: every chicken is injected following vaccine respectively: escherichia coli multivalence Seedling and pseudorabies inactivated vaccine, an injection volume 0.5ml/ chicken of every kind of vaccine and vaccine;
D. the back is to laying hen immunity for the third time around, and its method: every chicken is injected following vaccine respectively: transmissible gastroenteritis vaccine, rotavirus diarrhoea Seedling, epidemic diarrhea vaccine, 0.5ml/ chicken of every kind of vaccine injection amount;
E. six all backs are to the 4th immunity of laying hen, its method: every chicken is injected following vaccine and vaccine respectively: Salmonella multivalence Seedling, colibacillus multivalence bacterium, clostridieum welchii multivalence bacterium or rabbit pestilence-pasteurellosis bacillus-clostridieum welchii three inactivated bacteria, sheep braxy-lamb dysentery, struck-the intestinal toxenia-black disease 5-linked Seedling, the transmissible gastroenteritis vaccine, pseudorabies go out words Seedling and rotavirus diarrhea Seedling, the injection volume of every kind of vaccine and vaccine is a 0.5m1-1.0/ chicken;
F. carrying out the yolk antibody immunology detection after eight weeks is K88, K99 in the multi-joint multivalent antibody, 987P antibody agglutination titer 1: 160-1: the high immune egg of multi-joint multivalence is collected in 640 backs, under 16 ℃ of conditions, preserve stand-by, if detect defective, repeating step (e), again immunity, qualified until detecting.
(2) multi-joint multivalent antibody is purified
A. the high immune egg of multi-joint multivalence that step (1) is obtained is sterilized earlier, smashes egg and separates, and obtains egg white and yolk, and wherein egg white is spray-dried, makes the egg white powder;
B. 2-10 sterile deionized water and the 0.1-1.0NHCl doubly that in (a) step yolk, adds yolk weight, make pH value to 5.0-5.8, add NaCl, concentration is to 0.5-0.9% (W/W), add Polyethylene Glycol 6000 again, concentration stirs then after 10-20 minute and left standstill 0.5-24 hour, when the controlling liquid temperature is 4-20 ℃ to 3.5-5.0% (W/V), descended centrifugal 10-30 minute at 3000-15000 rev/min, obtain supernatant and precipitate, precipitate is spray-dried, obtains powdery yolk;
C. in (b) supernatant in step, add Polyethylene Glycol-6000, concentration is to 12-15% (W/V), add 0.1-1.0N NaOH again, make pH value to 6.8-7.5, stirred 10-20 minute, left standstill 0.5-24 hour, when the controlling liquid temperature reaches 4 ℃, descended centrifugal 20-40 minute at 3000-15000 rev/min, abandoning supernatant, precipitate is multi-joint multivalent antibody semifinished product;
D. multi-joint multivalent antibody semifinished product is dissolved in the aseptic but ionized water, repeat (c) step process again, get precipitation, carrying out antibody titer measures, K88, K99,987P antibody agglutination titer reach 1: 320 ∽ and promptly obtain purified multi-joint multivalent antibody at 1: 2560, and the amount of described sterile deionized water is 2-10 a times of multi-joint multivalent antibody semifinished product weight;
(3) produce Chinese medicine dry powder
The Chinese herbal medicine more than five kinds or five kinds that is selected from Cortex Phellodendri, Cacumen Platycladi, Rhizoma Coptidis, Cortex Fraxini, the Radix Pulsatillae, Rhizoma Atractylodis, the Radix Aucklandiae, Radix Sophorae Flavescentis, Herba Plantaginis, the Rhizoma Alismatis extracts by following process respectively, makes dry powder:
A. cold water soak 1-5 hour used in raw material of Chinese medicine chopping, clean back, fully soak into the 5-8 water doubly that the back adds raw material weight to the medicine heart, be heated to boiling back slow fire boiling, decocted 30-60 minute for the first time, pour out medicinal liquid, and then carry out twice decoction, decoct amount of water is 5 times of water of raw material weight at every turn, decocts 1-2 hour, then three medicinal liquids are mixed and obtain admixing medical solutions, add 3 times of water of raw material weight in the remaining medicinal residues again, decocted 30 minutes, medicinal liquid is used for the next group medicine and decocts use;
B. will go on foot poly-(a) admixing medical solutions, at negative pressure 3-8 kPa, temperature 40-80 ℃ following concentrating under reduced pressure, to the water content of dry be 10-15%, the centrifugal again soil of removing;
C. the material removed behind the soil of step (b) carries out spray drying on drying machine with centrifugal spray, promptly obtains Chinese medicine dry powder, described spray dryer operating condition: inlet temperature 150-280 ℃, outlet temperature 70-90 ℃, rotating speed 12000-30000 rev/min;
(4) produce the two qi factor compound formulations of antibody Chinese medicine
The purified multi-joint multivalent antibody that step (2) is made; the antibody synergistic protector; the Chinese medicine dry powder that step (3) is produced respectively and comprise fruit oligose; manna oligosaccharide; zymosan is at interior two qi factor saccharides; behind mixing; add sterile deionized water; weight concentration to mixture reaches 25-30%; emulsifying on high-speed emulsifying machine or homogenizer then; filter; after spray drying on the drying machine with centrifugal spray, cross 3-5 number sieve then; carry out quality examination at last; packing; warehouse-in, described spray dryer operating condition: inlet temperature 150-220 ℃; outlet temperature 65-90 ℃; rotating speed 12000-30000 rev/min; negative pressure 10-80 handkerchief.
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