CN102727631A - Immunostimulatory injection for livestock - Google Patents

Immunostimulatory injection for livestock Download PDF

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Publication number
CN102727631A
CN102727631A CN2012102240566A CN201210224056A CN102727631A CN 102727631 A CN102727631 A CN 102727631A CN 2012102240566 A CN2012102240566 A CN 2012102240566A CN 201210224056 A CN201210224056 A CN 201210224056A CN 102727631 A CN102727631 A CN 102727631A
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injection
liquid
immune activation
ethanol
adds
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Inventor
陈益德
秦斌
胡学全
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CHONGQING JINBANG ANIMAL PHARMACEUTICAL Co Ltd
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CHONGQING JINBANG ANIMAL PHARMACEUTICAL Co Ltd
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Abstract

The invention relates to an immunostimulatory injection for livestock. The injection can be used as a diluent to enhance immune effects of vaccine especially serum and strongly enhance the antibacterial efficacy of the antibiotic powder injection; and the injection can be individually used to protect liver, promote bile flow, bring down a fever and improve the growth performance of animal bodies. The invention is characterized in that immunostimulatory injection is prepared by the following steps of: taking 10-20 g of Radix Astragali and 5-10 g of dried orange peel, slicing, decocting, concentrating by the use of ethanol to prepare a liquid A for standby; cutting off 5-10 g of radix bupleuri, adding water and distilling, dissolving by adding PEG 400 so as to prepare a liquid B for standby; adding the liquid B into the liquid A, adding injection water to 85-95 ml, using a pH conditioning agent, adding 0.1-0.2 g of active carbon, slightly boiling for 1 h, standing until it cools, adding 1 ml of benzyl alcohol for a constant volume of 100 ml; filtering, embedding, and sterilizing. The injection is produced at low cost, has good effect when singly used or used as a diluent, and especially has substantial synergism for ceftiofur sodium.

Description

Immune activation injection for animals
Technical field
The present invention relates to a kind of injection, especially can be used as the injection that the injection diluent uses or independent injection is used.
Background technology
In the prevention and treatment of livestock and poultry, used various types of lyophilizing shape bacterin preparations and Powdered powder injection formulation, when clinical use, need injection of dilution back or drop in proportion.At present the diluent that often uses of veterinary has two kinds of injection normal saline and glucose injections, and they all have weak point on function of use.Glucose injection can be taken into account to animal body in the dilution medicine energy is provided; But its pH value is about 3.0; Best PH (pH=7-8) far below dilution vaccine and most of antibiotics powder pin; The pH value of injection normal saline is high slightly to be 4-5, does not also reach best use value and energy can't be provided.To such an extent as to clinical use link has the veterinarian independently to add the pH value that sodium bicarbonate improves medicinal liquid.Use inconvenient like this.
Problems such as in addition, injection normal saline and glucose injection are simple owing to composition, and production firm is numerous, and existence is carried disease germs qualitatively, pH value changes, the holding time is short.
Chinese herbal medicine is the human material of using the earliest; Can play the effect of preventing and curing diseases; And toxic and side effects is little; Have no drug resistance, can in edible animal products, not produce hazard residue, problems such as the pathogenic microorganism that also can avoid using chemicals to cause in a large number develops immunity to drugs, livestock products drug residue and environmental pollution.Traditional theory to concern between the rerum natura of natural Chinese medicinal herb, thing flavor, thing is taken as the leading factor; Be aided with the injection that modern Chinese medicine effective ingredient extractive technique and drug preparation technique process and be referred to as Chinese medicine injection, this series products receives relevant expert scholar's concern and high praise day by day because of advantages such as its diverse in function, pure natural, environmental protections.
Summary of the invention
Main purpose of the present invention aims to provide the multiduty Chinese medicine immune activation of a kind of pure natural injection, and this injection is done the diluent use can strengthen the particularly immune effect of serum of vaccine, the antibacterial efficacy of powerful antibiotic potentiator injectable powder; But inject hepatic cholagogic separately, bring down a fever, improve the animal body growth performance.
For realizing the foregoing invention purpose, the technical scheme that the present invention adopted is: a kind of immune activation injection for animals is characterized in that:
Radix Astragali 10-20g, Pericarpium Citri Reticulatae 5-10g, section adds 5 times of weight water for injection decoctings and boils 2 times, and 2 hours for the first time, 1 hour for the second time; Collecting decoction filters, and filtrating is concentrated into 2 times of Chinese crude drug weight water yields, slowly adds ethanol when being chilled to 40 ℃, makes to contain the alcohol amount and reach 75%; Fully stir, left standstill 12 hours, it is an amount of that leaching supernatant, residue add 75% ethanol, stirs; Left standstill 12 hours, and filtered, merge ethanol liquid, reclaim ethanol to there not being the alcohol flavor, it is subsequent use to make A liquid;
Radix Bupleuri 5-10g cuts off, and adds water temperature and soaks, and through 4 times of weight water distillations, collects distillate just, and redistillation is collected double distilled liquid again, adds the PEG400 of 20-40ml, stirs oil is dissolved fully, and it is subsequent use to make B liquid;
B liquid is added in the A liquid, add water for injection to 85-95ml, uses the pH regulator agent to regulate pH and be 7.0-7.5, add active carbon 0.1-0.2g, little boiling 1 hour put coldly, is settled to 100ml behind the adding benzyl alcohol 1ml;
Filter, embedding, sterilization promptly gets.During fill, can fill in cillin bottle, ampoule bottle, vial, loading amount for example 5ml commonly used, 10ml, 100ml etc.
115 ℃ on described injection warp, pressure 0.2MPa sterilization 30 minutes.
Described pH regulator agent is the sodium hydroxide solution of 0.5mol/L or the hydrochloric acid solution of 0.5mol/L.During actual fabrication, according to circumstances regulate, the pH value height goes beyond the scope, and the acceptable salts acid solution is regulated, and pH value is lower than this scope, and the available hydrogen sodium hydroxide solution is regulated.
Preferably, described Radix Astragali 15-20g, Pericarpium Citri Reticulatae 7-10g, Radix Bupleuri 7-10g.
Preferably, described PEG400 consumption is 30-40ml.
Benzyl alcohol is the preferred specific antiseptic of the present invention.PEG400 is preferred specific fat-soluble solvent, and pharmaceutically active ingredients in a lot of such as protein, aminoacid, polysaccharide, vitamin, trace element, volatile oil are had good affinity, and helps the pH value stability of preparation.
In the present invention; Radix Astragali major function is for strengthening animal body specific immune function and non-specific immunity, absorbs in animal body to be converted into the function that can stimulate macrophage and T cell behind the astragalus polysaccharides, makes the E ring form the cell number increase; Induce cytokine; Promote that interleukin induces, and make animal body produce endogenous interferon, thereby reach antiviral purpose.Identical with the antiviral mechanism of vaccine, can induce the cooperation of body immune system, reach the synergetic immunity potentiation.Better dilution effect is embodied on the serum class preparation, and the non-specific immunity of the Radix Astragali can improve the serum antibody specific immunity in the deficiency of effect on the persistent period.In addition the antiinflammatory of the Radix Astragali, diuresis, blood pressure lowering, analgesic, multiple biological activity such as protect the liver, have the effect of heat clearing and damp drying, eliminating fire and detoxication, be applicable to the auxiliary treatment of animal viral disease and bacterial disease.
The Radix Bupleuri of selecting for use among the present invention is because its volatile oil has the effect of antiinflammatory, regulate body temperature, antipyretic-antalgic, compares with synthetic antipyretic analgesic such as aminophenazone, dipyrones, can not damage the self-resistance of animal body, brings down a fever and does not rebound.Selecting Pericarpium Citri Reticulatae for use, is because it has the function that strengthening the spleen is good for the stomach that helps digestion of regulating the flow of vital energy, and can improve the animal body fluid balance, promotes animal appetite, improves feedstuff digestive utilization ratio and animal product quality.
The advantage of immune activation injection of the present invention is in particular in:
1. use approach is various, can dilute preparations such as livestock and poultry cultivation vaccine commonly used, serum, antibiotic powder pin, has health care and the antiinflammatory of the growing state that improves poultry, the function of bringing down a fever of regulate body temperature during independent injection.
2, natural Chinese medicines preparation toxic and side effects is little, has no drug resistance, and can in edible animal products, not produce hazard residue, problems such as the pathogenic microorganism that also can avoid using chemicals to cause in a large number develops immunity to drugs, livestock products drug residue and environmental pollution.
3, reasonably extract and the preparation process operation very convenient simple, cost control is low, help the commercial production needs.
4, stable p H-number scope is fit to the antibiotic environment for use of antibiotic powder pin, can strengthen its sterilizing function, and is particularly remarkable, for example remarkable to the potentiation of ceftiofur sodium to beta-lactam, Tetracyclines powder pin synergistic effect.The toxic and side effects that reduction simultaneously or counteracting antibiotic produce when antibiotic.
5, the non-specific immunity to vaccine has synergistic function, especially to suffering from immunosuppressive disease or immune unresponsive poultry are respond well; Specific immune function defective to serum has complementary action, activates the animal body active immune function, prolongs the time of immunoprotection.
The specific embodiment
The Chinese crude drug Radix Astragali that uses among the embodiment, Radix Bupleuri, Pericarpium Citri Reticulatae (medicinal decoction pieces) are purchased the prepared slices of Chinese crude drugs factory in the Chongqing City; Benzyl alcohol (AR) is purchased in ShouGuang Luyuan Salt Chemical Co., Ltd.; PEG400 (pharmaceutical grade) and medical ethanol are purchased the chemical industry company limited in Gutian, Nanjing, and activated carbon is purchased the activated carbon Manufacturing Co., Ltd in the Zhong Mountain, Chongqing.
Embodiment one
Immune activation injection (1ml is equivalent to crude drug in whole 0.4g)
1, prescription
Radix Astragali 20g, Radix Bupleuri 10g, Pericarpium Citri Reticulatae 10g, pH regulator agent 0.2g, activated carbon 0.2g, PEG400 consumption 40ml, benzyl alcohol 1ml, water for injection adds to 100ml.
2: method for preparing
The first step: get the recipe quantity Radix Astragali, Pericarpium Citri Reticulatae, section adds 5 times of weight water for injection decoctings and boils 2 times, and 2 hours for the first time, 1 hour for the second time; Collecting decoction filters, and filtrating is concentrated into 2 times of Chinese crude drug weight water yields, slowly adds ethanol when being chilled to 40 ℃, makes to contain the alcohol amount and reach 75%; Fully stir, left standstill 12 hours, it is an amount of that leaching supernatant, residue add 75% ethanol, stirs; Left standstill 12 hours, and filtered, merge ethanol liquid, reclaim ethanol to there not being the alcohol flavor, it is subsequent use to make A liquid.
Second step: get recipe quantity Radix Bupleuri and cut off, add water temperature and soak, through 4 times of weight water distillations, collect distillate just, redistillation is collected double distilled liquid again, adds recipe quantity PEG400, stirs oil is dissolved fully, and it is subsequent use to make B liquid.
The 3rd step: B liquid is added in the A liquid, add water for injection to 95ml, using the sodium hydroxide solution regulation system pH of 0.5mol/L is 7.5; Add the recipe quantity active carbon, little boiling 1 hour put cold; Be settled to 100ml after adding the recipe quantity benzyl alcohol; Filter, embedding, 115 ℃ on warp, pressure 0.2MPa sterilization promptly got in 30 minutes.
Embodiment two
Immune activation injection (1ml is equivalent to crude drug in whole 0.3g)
1, prescription
Radix Astragali 15g, Radix Bupleuri 7.5g, Pericarpium Citri Reticulatae 7.5g, pH regulator agent 0.2g, activated carbon 0.15g, PEG40030ml, benzyl alcohol 1ml, water for injection adds to 100ml.
2: method for preparing: identical with embodiment 1 said method.
Embodiment three
Immune activation injection (1ml is equivalent to crude drug in whole 0.2g)
1, prescription
Radix Astragali 10g, Radix Bupleuri 5g, Pericarpium Citri Reticulatae 5g, pH regulator agent 0.1g, activated carbon 0.1g, PEG40020ml, benzyl alcohol 1ml, water for injection adds to 100ml.
2: method for preparing: identical with embodiment 1 said method.
One, the accelerated stability test of immune activation injection
1, materials and methods: get embodiment 1-3 immune activation injection; Carry out hot and humid high light accelerated tests according to " Chinese veterinary drug allusion quotation " appendix medicine stability of version experimental technique in 2010; Press commercially available back; In the medicine stability experimental box (Chongqing immortality experimental apparatus factory) of 40 ± 2 ℃ of temperature, relative humidity 75 ± 5%, illumination 4500 ± 500LX, placed 6 months; Take a sample respectively once the 1st, 2,3,6 the end of month at experimental session, color, pH value, the content of injection are investigated.
2, result: can know that by table 1 after 6 months, color, pH value, each component content have no significant change immune activation injection of the present invention in accelerated test, have good stability,
The accelerated tests result of table 1, immune activation injection for animals
Figure BDA00001835247300051
Figure BDA00001835247300061
Two, the immune activation injection is to the influence test of newcastle disease and infections bursal disease vaccine immunity power
Use embodiment 1 injection to dilute preparation chicken ND I system, ND IV system, ND oil-emulsion vaccine and IBD freeze-dried vaccine respectively; In 15 days, successively being inoculated in 1 group of (35) healthy non-immunized chicks by immune programme for children is experimental group 1; With method operation embodiment 2, routine 3 injection, in 15 days, successively being inoculated in 2 groups of (35 every group) healthy non-immunized chickses by immune programme for children is experimental group 2 and 3.Use the injection normal saline to dilute chicken ND I system, ND IV system, ND oil-emulsion vaccine and IBD freeze-dried vaccine respectively simultaneously, in 15 days, successively be inoculated in 1 group of (35) healthy non-immunized chicks as matched group by immune programme for children.With ND, IBD antibody titer in agar gel diffusion test (AGP) the monitoring serum, the variation to each group chicken spleen, bursa of Fabricius's weight simultaneously dynamic observes after the 4th immunity finishes 10 days.Testing result: each embodiment group serum N D, IBD antibody titer are significantly higher than matched group (P<0.05), and wherein the antibody titer with 1 group of embodiment is the highest; In addition, 3 groups of spleens of embodiment 1-example and bursa of Fabricius's weight are significantly higher than matched group (P<0.05).Test shows that the immunological adjuvant that the immune activation injection can be used as the chicken vaccine improves the immunity of chicken, and embodiment is best for 1 group.
Table 2, immune activation injection influence the result of the test table to newcastle disease and infections bursal disease vaccine immunity power
Implement group number IBD tires ND tires Spleen (g/kg) Thymus (g/kg)
Experimental group 1 122±2.7 256±5.4 2.21±0.11 0.62±0.09
Experimental group 2 113±2.1 238±5.2 2.17±0.09 0.59±0.11
Experimental group 3 108±2.2 230±5.0 2.18±0.12 0.57±0.08
Matched group 71±1.8 139±3.9 1.58±0.02 0.54±0.09
Three, the immune activation injection is to the synergism test of antibiotic powder pin injection ceftiofur sodium
1, method and material
Choose pig farm, Yunmen town, Hechuan; Veterinary clinic is diagnosed as the sick pig that pig streptococcicosis infects; Be divided into three groups of A, B, C, D at random, the A group adopts embodiment 1 immune activation injection dilution injection ceftiofur sodium, and the B group adopts embodiment 2 immune activation injection dilution injection ceftiofur sodium; The C group adopts embodiment 3 immune activation injection dilution injection ceftiofur sodium, and glucose injection dilution injection ceftiofur sodium is adopted in the contrast of D group.Every group all by ceftiofur 3mg/kg intramuscular injection, injection on the one once, logotype 3 days.
2, decision procedure as a result
Observe the treatment case in after 3 days, pay a return visit and the record state of an illness.
Cure: the complete obiteration of 3 future trouble poultrys of medication disease, spirit, body temperature, appetite recover normal, and urine feces is normal.
Effectively: 3 future trouble poultrys of medication disease disappears basically, and spirit, body temperature, appetite make moderate progress, and urine feces is normal.
Invalid: 3 future troubles of medication poultry disease does not disappear, and sb.'s illness took a turn for the worse or dead, and urine stool colour, character are undesired.
3, result: can find out from table 3, use the antibiotic powder pin of medicine immune activation injection dilution of the present invention, the treatment bacterial infection of livestock is had significant curative effect, cure rate and effective percentage all are significantly higher than the matched group that uses the glucose injection dilution.Wherein use the experimental group effective percentage of product of the present invention to reach 98%, cure about 90%; And matched group D cure rate is merely 52.94%, effective percentage 81.88%.
The synergism test of table 3, injection ceftiofur sodium
Figure BDA00001835247300071
Four, the immune activation injection is separated heat test
1, method and material
1.1 medicine
The immune activation injection adopts the present invention to prepare routine 1-example 3.
Analgin injection, Chongqing City animal pharmaceutical factory produces.
0.9% normal saline, laboratory is provided for oneself.
The typhoid fever attenuated vaccine is purchased in Chinese biological technology group company.
1.2 laboratory animal: get body weight 1.5-2.0kg, body temperature is divided into 5 groups at random 50 of 39.0 ± 5 ℃ healthy rabbits for three days on end, 10 every group, male and female half and half.
1.3 implementation process: preceding 3 groups of rabbit are injected the immune activation injection of embodiment 1-example 3 respectively, and ID is pressed 0.1ml/kg.Matched group injection analgin injection, every ID is pressed 0.1ml/kg.Blank control group is injected 0.9% normal saline, and every ID is pressed 0.1ml/kg.Each is organized rabbit and injects the typhoid fever of 1ml/kg ear vein injection according to dosage attenuated vaccine after 30 minutes, measures the anus temperature in the time at vaccinate front and back 30,60,90,120,150,180,210,240min then, record data, and the result sees table 4.
2, result: can find out from table 4; A little less than the injection typhoid fever behind the malicious Seedling 30min, respectively organize that rabbit body temperature significantly rises, 60min reaches peak value constantly; The sick rabbit body temperature of the immune activation injection of embodiment 1-example 3 basic controlling when 120min is normal; Also the sick rabbit body temperature of basic controlling is normal when 180min for analgin injection, and the immune activation injection is less in each time period temperature fluctuation difference, and is analgesic respond well and be superior to analgin injection.
Table 4, the analgesic result of the test of fever in rabbit (℃, ± S)
Figure BDA00001835247300081

Claims (5)

1. immune activation injection for animals is characterized in that:
Radix Astragali 10-20g, Pericarpium Citri Reticulatae 5-10g, section adds 5 times of weight water for injection decoctings and boils 2 times, and 2 hours for the first time, 1 hour for the second time; Collecting decoction filters, and filtrating is concentrated into 2 times of Chinese crude drug weight water yields, slowly adds ethanol when being chilled to 40 ℃, makes to contain the alcohol amount and reach 75%; Fully stir, left standstill 12 hours, it is an amount of that leaching supernatant, residue add 75% ethanol, stirs; Left standstill 12 hours, and filtered, merge ethanol liquid, reclaim ethanol to there not being the alcohol flavor, it is subsequent use to make A liquid;
Radix Bupleuri 5-10g cuts off, and adds water temperature and soaks, and through 4 times of weight water distillations, collects distillate just, and redistillation is collected double distilled liquid again, adds the PEG400 of 20-40ml, stirs oil is dissolved fully, and it is subsequent use to make B liquid;
B liquid is added in the A liquid, add water for injection to 85-95ml, uses the pH regulator agent to regulate pH and be 7.0-7.5, add active carbon 0.1-0.2g, little boiling 1 hour put coldly, is settled to 100ml behind the adding benzyl alcohol 1ml;
Filter, embedding, sterilization promptly gets.
2. a kind of immune activation injection for animals according to claim 1 is characterized in that: 115 ℃ on described injection warp, pressure 0.2MPa sterilization 30 minutes.
3. a kind of immune activation injection for animals according to claim 1 is characterized in that: described pH regulator agent is the sodium hydroxide solution of 0.5mol/L or the hydrochloric acid solution of 0.5mol/L.
4. according to claim 1 or 2 or 3 described a kind of immune activation injection for animals, it is characterized in that: described Radix Astragali 15-20g, Pericarpium Citri Reticulatae 7-10g, Radix Bupleuri 7-10g.
5. a kind of immune activation injection for animals according to claim 4, it is characterized in that: described PEG400 consumption is 30-40ml.
CN2012102240566A 2012-06-30 2012-06-30 Immunostimulatory injection for livestock Pending CN102727631A (en)

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Application publication date: 20121017