CN1426816A - Veterinarian virus kind biological product heat resisting freeze drying protective agent and its preparation technique - Google Patents

Veterinarian virus kind biological product heat resisting freeze drying protective agent and its preparation technique Download PDF

Info

Publication number
CN1426816A
CN1426816A CN01138871A CN01138871A CN1426816A CN 1426816 A CN1426816 A CN 1426816A CN 01138871 A CN01138871 A CN 01138871A CN 01138871 A CN01138871 A CN 01138871A CN 1426816 A CN1426816 A CN 1426816A
Authority
CN
China
Prior art keywords
component
sorbitol
gelatin
sodium glutamate
freeze
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN01138871A
Other languages
Chinese (zh)
Other versions
CN1168503C (en
Inventor
卫广森
王文成
张万林
Original Assignee
卫广森
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 卫广森 filed Critical 卫广森
Priority to CNB011388714A priority Critical patent/CN1168503C/en
Publication of CN1426816A publication Critical patent/CN1426816A/en
Application granted granted Critical
Publication of CN1168503C publication Critical patent/CN1168503C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Landscapes

  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

A freeze-dried high-temp. resistant protecting agent for virus-type biologic products for veterinary medicine is prepared from several components through proportionally mixing. It features that each of its components is sterilized separately. For the components which can be sterilized under high temp., they are dissolved in distilled water according to the proportion of formulation and are sterilized at 116 deg.C for 30-40 min; and for those which do not resist the high temp., they are also dissolved in distilled water according the proportion of formulation and are filtered with 0.22 micron pore diameter filter membrane to remove bacteria; and then the two parts are mixed to obtain the freeze-dried high-temp. resistant, protecting agent. The mentioned two parts are added to the virus antigen liquid according to a proportion of 1:1 and after packaging, they are freeze-dried. The product can be stored at 2-8 deg.C for 24 months.

Description

Veterinarian virus kind biological product heat resisting freeze drying protective agent and preparation technology
Affiliated technical field
The present invention relates to the Freeze Drying Technique of biological product, preservation adjuvant and manufacture method thereof.
Background technology
China's veterinary biological product protective agent commonly used at present is mainly 5% sucrose skim milk and 5-10% sucrose, the 1.5-3% gelatin, and goods require cryopreservation (below 15 ℃), and the storage life of 2-8 ℃ of condition only 3-9 month must use up at normal temperatures as early as possible.This is just for the preservation of veterinary biological product, transportation, use etc. bring many difficulties and inconvenience, simultaneously owing to must cryopreservation causing energy resource consumption and storage cost big.
At present, the flourishing in the world biological freeze-dried products of national veterinary almost all is that 2-8 ℃ of preservation is more than 24 months.But the not play-by-play of square method.Chinese patent CN1176827A " a kind of manufacture method of freeze-dried live vaccine for animal use " proposes to adopt with polyvinylpyrrolidone, sodium carboxymethyl cellulose; tamarind gum; sodium glutamate; trehaloses etc. are the freeze drying protectant that the formulated of main matrix freeze drying protectant becomes; the method that freeze-drying curve that employing adapts with it and newcastle disease vaccine virus antigen are made the newcastle disease freeze-dried live vaccine, but this Seedling long preservation under 2-8 ℃ of condition.
Summary of the invention
Veterinarian virus kind biological product heat resisting freeze drying protective agent and preparation technology, comprise that various heat-resisting lyophilized protecting agents with Veterinarian virus kind biological product are respectively by component, mixed, it is characterized in that each protectant active princlple is handled degerming respectively:, sterilized 30-40 minute for 116 ℃ to can autoclavedly being dissolved in the distilled water in the preparation ratio; The component of non-refractory also is dissolved in the distilled water with aperture 0.22 μ m membrane filtration degerming in the preparation ratio; After finishing degerming respectively two kinds of compositions are mixed, be the lyophilizing heat resisting protective, add in the virus antigen liquid in 1: 1 ratio during use, carry out lyophilization after the packing.
Preparation technology of the present invention is the characteristics according to different virus, create the combination of different component, different proportion, technological requirement is formulated rational freeze-drying curve routinely, to guarantee the biological activity of goods, various preparation of the present invention is preserved more than 24 months under 2-8 ℃ of condition, all can reach every index of regulation in " People's Republic of China's veterinary biological product quality standard ".
The specific embodiment
Veterinarian virus kind biological product heat resisting freeze drying protective agent, protectant component comprises gelatin commonly used, sucrose, defatted milk powder, dextrin, it is characterized in that the component proportioning of various heat-resisting lyophilized protecting agents is: the weak malicious freeze dried vaccine of (1) newcastle disease: gelatin 1.5-2%, sucrose 5-6%, dextrin 5-10%, PVP (K90) 2-5%, sorbitol 2%, sodium glutamate 1-2%; (2) the weak poison of infectious bursal disease (B87) freeze dried vaccine: defatted milk powder 5%, dextrin 5%, beef peptone 1-3%, sucrose 5-6%, sorbitol 2%, sodium glutamate 1-3%, Vc0.1%; (3) infectious bronchitis of chicken (H120, H52, Kidney infectious bronchitis W93) freeze dried vaccine: gelatin 1.5-2%, bovine serum albumin 1-2%, sucrose 5-6%, PVP (K90) 5%, casein peptone 2%, sorbitol 1-3%, sodium glutamate 1-2%, Vc0.1-0.3%; (4) newcastle disease, infectious bronchitis of chicken (H120, H52) bigeminy freeze dried vaccine: gelatin 2%, dextrin 6%, bovine serum albumin 1-2%, sucrose 5-6%, PVP (K90) 3%, casein peptone 1-2%, sorbitol 2%, sodium glutamate 1%, Vc0.2-0.3%; (5) infectious laryngotracheitis of chicken freeze dried vaccine: gelatin 2%, dextrin 5%, lactose 5-6%, sorbitol 2%, arginase 12 %, sodium glutamate 1%, Vc0.1%; (6) swine fever bovine testicle cell Seedling: gelatin 3%, lactose 5-6%, beef peptone 2%, PVP (K90) 3%, sorbitol 2%, sodium glutamate 2%, Vc0.1%; (7) fowlpox freeze-dried vaccine: gelatin 3%, EDTA2%, lactose 5-6%, beef peptone 2%, bovine serum albumin 1%, PVP (K90) 5%, sorbitol 2%, sodium glutamate 1%, Vc0.1%; (8) marek isease turkey herpes virus freeze-dried vaccine: gelatin 1.5%, EDTA2%, sucrose 7.6%, beef peptone 1%, bovine serum albumin 1%.Be the dry component in above-mentioned each preparation, percentage ratio residue part is distilled water.
The preparation technology of Veterinarian virus kind biological product heat resisting freeze drying protective agent, comprise various heat-resisting lyophilized protecting agents respectively by component, mixed, it is characterized in that each protectant active princlple is handled degerming respectively: to can be autoclaved being dissolved in the distilled water in ratio separately, 116 ℃ of sterilizations 30-40 minute; The component of non-refractory also is dissolved in the distilled water in proportion with aperture 0.22 μ m membrane filtration degerming; After finishing degerming respectively two kinds of compositions are mixed, be the lyophilizing heat resisting protective, add in the virus antigen liquid in 1: 1 ratio during use, carry out lyophilization after the packing.But protectant active princlple is divided into autoclaving and thermo-labile filtering two classes by degerming technology: (1) but the weak malicious freeze dried vaccine autoclaving component of newcastle disease be: gelatin, sucrose, dextrin, PVP (K90); The component of thermo-labile filtration sterilization is: sorbitol, sodium glutamate; (2) the weak poison of infectious bursal disease (B87) but freeze dried vaccine autoclaving component be: defatted milk powder, dextrin, beef peptone, sucrose; The component of thermo-labile filtration sterilization is: sorbitol, sodium glutamate, Vc; (3) infectious bronchitis of chicken (H120, H52, Kidney infectious bronchitis W93) but freeze dried vaccine autoclaving component be: gelatin, sucrose, PVP (K90), casein peptone; The component of thermo-labile filtration sterilization is: bovine serum albumin, sorbitol, sodium glutamate, Vc; (4) newcastle disease, infectious bronchitis of chicken (H120, H52) but bigeminy freeze dried vaccine autoclaving component be: gelatin, dextrin, sucrose, PVP (K90), casein peptone; The component of thermo-labile filtration sterilization is: bovine serum albumin, sorbitol, sodium glutamate, Vc; (5) but infectious laryngotracheitis of chicken freeze dried vaccine autoclaving component be: gelatin, dextrin, lactose; The component of thermo-labile filtration sterilization is: sorbitol, arginine, sodium glutamate, Vc; (6) but swine fever bovine testicle cell Seedling autoclaving component be: gelatin, lactose, beef peptone, PVP (K90); The component of thermo-labile filtration sterilization is: sorbitol, sodium glutamate, Vc; (7) but fowlpox freeze-dried vaccine autoclaving component be: gelatin, EDTA, lactose, beef peptone, PVP (K90); The component of thermo-labile filtration sterilization is: bovine serum albumin, sorbitol, sodium glutamate, Vc; (8) but marek isease turkey herpes virus freeze-dried vaccine autoclaving component be: gelatin, EDTA, sucrose, beef peptone; The component of thermo-labile filtration sterilization is: phosphorus potassium dihydrogen, dipotassium hydrogen phosphate, sorbitol, sodium glutamate, bovine serum albumin.
Technical parameter and detection method
1. the physical behavior of product, steriling test, mycoplasma check, exogenous virus check, specificity check, safety verification, residual moisture mensuration and vacuum are measured by the method and the standard of " People's Republic of China's veterinary biological product rules " and are undertaken.
2. lyophilization cycle is no more than 48h.
3. protectant toxicity test
Bird vaccine carries out each 20 of collunarium, eye dripping, drinking-water and subcutaneous injections by containing 10 times of amounts protecting dosage in the middle of the product respectively to 7 age in days healthy chicks, observes 20d, and chickling is all strong to live, and does not have any untoward reaction.
4. the viral level of each product is measured and standard
1) the weak malicious freeze-dried live vaccine of newcastle disease
(1) assay method:
A. make 10 times of serial dilutions by the real tissue mass that contains with sterile saline, get 3 suitable dilution factors, inoculate 5 of 10 age in days SPF Embryo Gallus domesticus in the allantoic cavity respectively, every embryo 0.1mL puts 37 ℃ and continues to hatch, the dead in the past Embryo Gallus domesticus of 48h discards to be disregarded, at the Embryo Gallus domesticus of 48-120h death, take out results Embryo Gallus domesticus liquid at any time, with same dilution Embryo Gallus domesticus liquid mixed in equal amounts, measure the red cell agglutination valency respectively.To 120h, get all embryos of living, gather in the crops Embryo Gallus domesticus liquid one by one, measure the red cell agglutination valency respectively, agglutination titer 〉=160 are judged to infection, calculate EID 50
B. press label and indicate plumage part, vaccine is diluted to 1 plumage part/0.1mL with sterile saline, remake 10 times of serial dilutions, other method is the same, calculates every plumage part EID at last 50Content.
(2) reach standard
A. after the lyophilizing viral loss rate less than 0.4 titre.
B. every plumage part viral level 〉=10 after the lyophilizing 6.7EID 50
C. the product after the lyophilizing is put 37 ℃ and is preserved 10d and 30d and carry out viral level and measure, rate of descent the former within 1 titre, the latter is within 2 titres.
D. the product after the lyophilizing is put 25 ℃ of preservation 30d, and the viral level rate of descent is within 0.6 titre.
E. product is put 2-8 ℃ of preservation 24 months, every plumage part viral level 〉=10 6.17EID 50Chicken
2) the weak poison of infectious bursal disease (B 87) the tissue freeze-dried vaccine
(1) assay method: vaccine is made 10 times of serial dilutions with sterile saline, and with allantocherion approach inoculation 10-12 age in days SPF Embryo Gallus domesticus, every embryo 0.2mL observes 168h, calculates ELD 50
3. protectant toxicity test
Bird vaccine carries out each 20 of collunarium, eye dripping, drinking-water and subcutaneous injections by containing 10 times of amounts protecting dosage in the middle of the product respectively to 7 age in days healthy chicks, observes 20d, and chickling is all strong to live, and does not have any untoward reaction.
4. the viral level of each product is measured and standard
1) the weak malicious freeze-dried live vaccine of newcastle disease
(1) assay method:
A. make 10 times of serial dilutions by the real tissue mass that contains with sterile saline, get 3 suitable dilution factors, inoculate 5 of 10 age in days SPF Embryo Gallus domesticus in the allantoic cavity respectively, every embryo 0.1mL puts 37 ℃ and continues to hatch, and dead Embryo Gallus domesticus discards and disregards before the 48h, 48 -The Embryo Gallus domesticus of 120h death takes out at any time, and results Embryo Gallus domesticus liquid with same dilution Embryo Gallus domesticus liquid mixed in equal amounts, is measured the red cell agglutination valency respectively.To 120h, get all embryos of living, gather in the crops Embryo Gallus domesticus liquid one by one, measure the red cell agglutination valency respectively, agglutination titer 〉=160 are judged to infection, calculate EID 50
B. press label and indicate plumage part, vaccine is diluted to 1 plumage part/0.1mL with sterile saline, remake 10 times of serial dilutions, other method is the same, calculates every plumage part EID at last 50Content.
(2) reach standard
A. after the lyophilizing viral loss rate less than 0.4 titre.
B. every plumage part viral level 〉=10 after the lyophilizing 6.7EID 50
C. the product after the lyophilizing is put 37 ℃ and is preserved 10d and 30d and carry out viral level and measure, rate of descent the former within 1 titre, the latter is within 2 titres.
D. the product after the lyophilizing is put 25 ℃ of preservation 30d, and the viral level rate of descent is within 0.6 titre.
E. product is put 2-8 ℃ of preservation 24 months, every plumage part viral level 〉=10 6.17EID 50Chicken
2) the weak poison of infectious bursal disease (B 87) the tissue freeze-dried vaccine
(1) assay method: vaccine is made 10 times of serial dilutions with sterile saline, and with allantocherion approach inoculation 10-12 age in days SPF Embryo Gallus domesticus, every embryo 0.2mL observes 168h, calculates ELD 50
(2) reach standard
A. after the lyophilizing viral loss rate less than 0.4 titre.
B. every plumage part viral level 〉=10 after the lyophilizing 3.7ELD 50
C. the product after the lyophilizing is put 37 ℃ and is preserved 10d and 30d and carry out viral level and measure, and the former rate of descent is within 0.2 titre, and the latter is within 0.4 titre.
D. product is put 25 ℃ to preserve 30d viral level rates of descent is within 0.2 titre.
E. product was preserved every plumage part viral level 〉=10 24 months at 2-8 ℃ 3.37ELD 50
3) infectious bronchitis of chicken (H 120, H 52, Kidney infectious bronchitis W 93) freeze dried vaccine
(1) assay method:
A. make 10 times of serial dilutions with normal saline by the real tissue mass that contains, get 3 dilution factors and respectively inoculate 5 of instar chicken embryos on the 10th, inoculation 0.1mL in every embryo allantoic cavity, putting 37 ℃ continues to hatch, the dead in the past Embryo Gallus domesticus of 24h discards to be disregarded, specificity lesion persons' such as in the embryo alive of still surviving according to inoculation back 24-144h dead germ and 144h, its fetus has dehydration, rolls up, dysplasia summation is calculated its EID 50
B. press label and indicate plumage part, vaccine is diluted to 1 plumage part/0.1mL with normal saline, do 10 times of serial dilutions again, following method is the same.
(2) reach standard
A. lyophilizing virus loss rate is again within 0.4 titre.
B. H after the lyophilizing 120, H 52Every plumage part viral level 〉=10 4.5EID 50Kidney infectious bronchitis W 93Every plumage part viral level 〉=10 5.5EID 50
C. product is put 37 ℃ of conditions preservation 10d and 30d, and the viral level rate of descent is respectively within 1 and 2 titre.
D. product is put 25 ℃ of conditions preservation 30d, and the viral level rate of descent is no more than 1 titre.
E. product is put 2-8 ℃ of preservation 24 months, H 120, H 52Every plumage part viral level 〉=10 3.5EID 50, Kidney infectious bronchitis W 93Every plumage part viral level 〉=10 4.67EID 50
4. newcastle disease, infectious bronchitis of chicken (H 120, H 52) bigeminal live vaccine
(1) assay method:
A. vaccine is diluted to 1 plumage part/0.5mL with normal saline, is respectively charged into 2 in vitro, every pipe 1mL.The 1st pipe adds the newcastle disease antiserum of equivalent, and the 2nd pipe adds the infectious bronchitis of chicken antiserum of equivalent.At room temperature and 1h, this moment, viral level was 0.1 plumage part/0.1mL, promptly 10 -1The 1st pipe continues 10 times of serial dilutions.Measure the infectious bronchitis of chicken part.The 2nd pipe continues 10 times of serial dilutions, measures the newcastle disease part, and its method is with infectious bronchitis of chicken and newcastle disease freeze-dried vaccine.
B. vaccine is contained tissue mass and is diluted to 500 times by real with normal saline, be respectively charged in 2 test tubes, every pipe 1mL, the 1st pipe adds the newcastle disease antiserum of equivalent, and the 2nd pipe adds equivalent infectious bronchitis of chicken antiserum.Be 10 this moment -3, remaking 10 times of serial dilutions at room temperature with behind the 1h, other method is the same.
(2) reach standard
Respectively with malicious freeze-dried vaccine a little less than the newcastle disease and infectious bronchitis of chicken freeze-dried vaccine effect.
5 infectious laryngotracheitis of chicken freeze dried vaccines
(1) method of inspection:
A. press label and indicate plumage part, vaccine is diluted to 1 plumage part 0.2mL with sterile saline, continue again to make 10 times of serial dilutions, get 3 suitable dilution factors, each allantocherion inoculation 10 -Instar chicken embryo was 5 on 11st, every embryo 0.2mL, and 5d is cultivated in the inoculation back, dissects, and observes pathological changes, and chick chorioallantoic membrane obviously thickens, and the canescence scab is arranged, and is judged to infection, calculates EID 50
B. by the real tissue mass 10 times of serial dilutions of sterile saline that contain, other method is the same.
(2) reach standard
A. lyophilizing virus loss rate is within 0.4 titre.
B. every plumage part viral level 〉=10 after the lyophilizing 3.7EID 50
C. product is put 37 ℃ of condition 10d and 30d, and viral loss rate is respectively within 1 and 1.5 titre.
D. product is put 25 ℃ of condition 30d, and viral loss rate is within 1 titre.
E. product 2-8 ℃ of condition preserved every plumage part viral level 〉=10 24 months 2.83EID 50
6 swine fever bovine testicle cell freeze dried vaccines
(1) detection method:
Imitate inspection with rabbit: press the dated head part of label, dilute suitable multiple with 750 times of every part vaccine dilutions or by the real antigen amount that contains with normal saline, 2 of ear vein injection rabbit, every 1mL changes to determine tiring of vaccine according to rabbit body temperature.
(2) reach standard
A. after the lyophilizing vaccine reach 7.5 ten thousand times qualified.
B. product is preserved 10d and 30d under 37 ℃ of conditions, and it is qualified that the effectiveness of product reaches 50,000 times and 40,000 times.
C. product is preserved 30d under 25 ℃ of conditions, and 50,000 times qualified.
D. product was preserved 24 months under 2-8 ℃ of condition, and the effectiveness of product is all more than 50,000 times.
7 fowlpox freeze-dried live vaccines
(1) detection method:
A. press label and indicate plumage part, with the normal saline dilution, 10 of allantocherion inoculation 11-12 day instar chicken embryos, every embryo 0.2mL (containing 1/100 using dosage).Behind the 96-120h, the chick chorioallantoic membrane edema thickens or the pox speckle occurs to be judged.
B. make 10 times of serial dilutions by the real antigen amount that contains with normal saline, get 3 suitable dilution factors, the every embryo 0.2mL of inoculation 11-12 age in days chick chorioallantoic membrane, thickening or the pox speckle occurs according to the chick chorioallantoic membrane edema behind the 96-120h is to infect to judge EID 50
(2) reach standard
A. lyophilizing virus loss rate is 0.4 below the titre.
B. EID after the lyophilizing 50All 〉=10 6.1EID 50/ 0.2mL.
C. product is preserved 10d and 30d under 37 ℃ of conditions, and viral loss rate is respectively within 0.8 and 1.2 titre.
D. product is preserved 30d under 25 ℃ of conditions, and viral loss rate is within 0.6 titre.
E. product was preserved 24 months 2-8 ℃ of condition, measured 10 embryos by " A " method and all obviously infected.
8 marek isease turkey herpes virus freeze dried vaccines
(1) detection method:
With " veterinary biologics rules ", press the method for plaque forming unit (PFU) and measure.
(2) reach standard
A. lyophilizing loss, the plaque slip is below 45%.
B. product is preserved 10d under 37 ℃ of conditions, and the plaque slip is below 50%.
C. product is preserved 20d under 25 ℃ of conditions, and the plaque slip is below 20%.
D. after the lyophilizing every plumage part viral level all greater than 5000PFU.
E. product was preserved 24 months 2-8 ℃ of condition, and every plumage part viral level is all greater than 3000PFU.

Claims (3)

1, a kind of Veterinarian virus kind is held the Tetramune heat-resisting lyophilized protecting agent, protectant component comprises sucrose commonly used, defatted milk powder, gelatin, dextrin, it is characterized in that various protectant component proportionings are: the weak malicious freeze dried vaccine of (1) newcastle disease: gelatin 1.5-2%, sucrose 5-6%, dextrin 5-10%, PVP (K90) 2-5%, sorbitol 2%, sodium glutamate 1-2%; (2) the weak poison of infectious bursal disease (B87) freeze dried vaccine: defatted milk powder 5%, dextrin 5%, beef peptone 1-3%, sucrose 5-6%, sorbitol 2%, sodium glutamate 1-3%, Vc0.1%; (3) infectious bronchitis of chicken (H120, H52, Kidney infectious bronchitis W93) freeze dried vaccine: gelatin 1.5-2%, bovine serum albumin 1-2%, sucrose 5-6%, PVP (K90) 5%, casein peptone 2%, sorbitol 1-3%, sodium glutamate 1-2%, Vc0.1-0.3%; (4) newcastle disease, infectious bronchitis of chicken (H120, H52) bigeminy freeze dried vaccine: gelatin 2%, dextrin 6%, bovine serum albumin 1-2%, sucrose 5-6%, PVP (K90) 3%, casein peptone 1-2%, sorbitol 2%, sodium glutamate 1%, Vc0.2-0.3%; (5) infectious laryngotracheitis of chicken freeze dried vaccine: gelatin 2%, dextrin 5%, lactose 5-6%, sorbitol 2%, arginase 12 %, sodium glutamate 1%, Vc0.1%; (6) swine fever bovine testicle cell Seedling: gelatin 3%, lactose 5-6%, beef peptone 2%, PVP (K90) 3%, sorbitol 2%, sodium glutamate 2%, Vc0.1%; (7) fowlpox freeze-dried vaccine: gelatin 3%, EDTA2%, lactose 5-6%, beef peptone 2%, bovine serum albumin 1%, PVP (K90) 5%, sorbitol 2%, sodium glutamate 1%, Vc0.1%; (8) marek isease turkey herpes virus freeze-dried vaccine: gelatin 1.5%, EDTA2%, sucrose 7.6%, beef peptone 1%, bovine serum albumin 1%, phosphorus potassium dihydrogen 0.52%, dipotassium hydrogen phosphate 1.64%, sorbitol 1%, sodium glutamate 1%; Be the dry component in above-mentioned each preparation, percentage ratio residue part is distilled water.
2, a kind of preparation technology of Veterinarian virus kind biological product heat resisting freeze drying protective agent, comprise right 1 described various protective agents respectively by component, mixed, it is characterized in that respectively each protectant active princlple being handled degerming respectively:, sterilized 30-40 minute for 116 ℃ to can autoclavedly being dissolved in the distilled water in the preparation ratio; The component of non-refractory also is dissolved in the distilled water with aperture 0.22 μ m membrane filtration degerming in the preparation ratio; After finishing degerming respectively two kinds of compositions are mixed, be the lyophilizing heat resisting protective, add in the virus antigen liquid in 1: 1 ratio during use, carry out lyophilization after the packing.
3, the preparation technology of Veterinarian virus kind biological product heat resisting freeze drying protective agent according to claim 2, but it is characterized in that various protectant active princlples are divided into autoclaving and thermo-labile filtering two classes by degerming technology: (1) but the weak malicious freeze dried vaccine autoclaving component of newcastle disease be: gelatin, sucrose, dextrin, PVP (K90); The component of thermo-labile filtration sterilization is: sorbitol, sodium glutamate; (2) the weak poison of infectious bursal disease (B87) but freeze dried vaccine autoclaving component be: defatted milk powder, dextrin, beef peptone, sucrose; The component of thermo-labile filtration sterilization is: sorbitol, sodium glutamate, Vc; (3) infectious bronchitis of chicken (H120, H52, Kidney infectious bronchitis W93) but freeze dried vaccine autoclaving component be: gelatin, sucrose, PVP (K90), casein peptone; The component of thermo-labile filtration sterilization is: bovine serum albumin, sorbitol, sodium glutamate, Vc; (4) newcastle disease, infectious bronchitis of chicken (H120, H52) but bigeminy freeze dried vaccine autoclaving component be: gelatin, dextrin, sucrose, PVP (K90), casein peptone; The component of thermo-labile filtration sterilization is: bovine serum albumin, sorbitol, sodium glutamate, Vc; (5) but infectious laryngotracheitis of chicken freeze dried vaccine autoclaving component be: gelatin, dextrin, lactose; The component of thermo-labile filtration sterilization is: sorbitol, arginine, sodium glutamate, Vc; (6) but swine fever bovine testicle cell Seedling autoclaving component be: gelatin, lactose, beef peptone, PVP (K90); The component of thermo-labile filtration sterilization is: sorbitol, sodium glutamate, Vc; (7) but fowlpox freeze-dried vaccine autoclaving component be: gelatin, EDTA, lactose, beef peptone, PVP (K90); The component of thermo-labile filtration sterilization is: bovine serum albumin, sorbitol, sodium glutamate, Vc; (8) but marek isease turkey herpes virus freeze-dried vaccine autoclaving component be: gelatin, EDTA, sucrose, beef peptone; The component of thermo-labile filtration sterilization is: phosphorus potassium dihydrogen, dipotassium hydrogen phosphate, sorbitol, sodium glutamate, bovine serum albumin.
CNB011388714A 2001-12-21 2001-12-21 Veterinarian virus kind biological product heat resisting freeze drying protective agent and its preparation technique Expired - Fee Related CN1168503C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CNB011388714A CN1168503C (en) 2001-12-21 2001-12-21 Veterinarian virus kind biological product heat resisting freeze drying protective agent and its preparation technique

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CNB011388714A CN1168503C (en) 2001-12-21 2001-12-21 Veterinarian virus kind biological product heat resisting freeze drying protective agent and its preparation technique

Related Child Applications (7)

Application Number Title Priority Date Filing Date
CNB2004100295841A Division CN1222320C (en) 2001-12-21 2001-12-21 Heat-resistant lyophilized protectant of lyophilized vaccine for chicken infectious laryngotracheitis and preparing process thereof
CNB2004100295837A Division CN1223375C (en) 2001-12-21 2001-12-21 Heat resisting lyophilized protectant for chicken infectious bronchitis (H120, H52, Kidney infectious bronchitis W93) lyophilized vaccine and preparing process thereof
CN 200410029587 Division CN1222314C (en) 2001-12-21 2001-12-21 Heat resisting lyophilized protectant for chicken Marek's disense turkey herpes virus lyophilized vaccine and preparing process thereof
CNB2004100295822A Division CN1233418C (en) 2001-12-21 2001-12-21 Heat-resisting lyophilized protectant for chicken newcastle disease, chicken infectious bronchitis (H120, H52) dual lyophilized vaccine and preparing process thereof
CN 200410029581 Division CN1251762C (en) 2001-12-21 2001-12-21 Heat resisting lyophilized protectant for chicken infections Fabianite bursa hypotpxicity (B87) lyophilized vaccine and preparing process thereof
CNB2004100295860A Division CN1253209C (en) 2001-12-21 2001-12-21 Heat-resistant lyophilized protectant of lyophilized vaccine for henpox and preparing process thereof
CN 200410029585 Division CN1211122C (en) 2001-12-21 2001-12-21 Heat-resisting lyophilized protectant for swine fever lapinized hyoptoxicity calf testicular cell vaccine and preparing process

Publications (2)

Publication Number Publication Date
CN1426816A true CN1426816A (en) 2003-07-02
CN1168503C CN1168503C (en) 2004-09-29

Family

ID=4674823

Family Applications (1)

Application Number Title Priority Date Filing Date
CNB011388714A Expired - Fee Related CN1168503C (en) 2001-12-21 2001-12-21 Veterinarian virus kind biological product heat resisting freeze drying protective agent and its preparation technique

Country Status (1)

Country Link
CN (1) CN1168503C (en)

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100384993C (en) * 2005-11-02 2008-04-30 浙江大学 Process for increasing stability of elastase of lichen spore bacillus ZJUEL31410
CN100418580C (en) * 2005-11-14 2008-09-17 中国农业科学院哈尔滨兽医研究所 Heat resistant freeze drying protectant for chicken Newcastle disease live vaccine and its prepn and application
CN102294028A (en) * 2011-05-24 2011-12-28 南京创启生物科技有限公司 Chicken newcastle disease missing-resistant heat-resistant drinking water-immunization tablet and preparation method thereof
CN102397556A (en) * 2011-05-23 2012-04-04 上海创宏生物科技有限公司 Heatproof protection agent for live vaccine of duck viral hepatitis (DVH), preparation method thereof and application thereof
CN102430126A (en) * 2011-12-31 2012-05-02 山东滨州博莱威生物技术有限公司 Heat-resistant stabilizer for tissue fluid lyophilization, as well as preparation method and application thereof
CN102626520A (en) * 2012-04-23 2012-08-08 青岛农业大学 Heat-resisting cryoprotectant of mink canine distemper live vaccine and preparation method thereof
CN102641504A (en) * 2012-04-14 2012-08-22 青岛农业大学 Heat-resistant freeze-drying protecting agent for vaccine and preparing method
CN102671207A (en) * 2012-05-30 2012-09-19 青岛农业大学 Newcastle disease and avian infectious bronchitis bigeminal live vaccine heat-resisting freeze-drying protective agent and preparation method
CN102671208A (en) * 2012-05-30 2012-09-19 青岛农业大学 Heat-resisting freeze-dried protective agent for live vaccine for chicken infectious bursal diseases and preparation method for heat-resisting freeze-dried protective agent
CN102671209A (en) * 2012-05-30 2012-09-19 青岛农业大学 Heat-resistant freeze-drying protective agent for newcastle disease live vaccines and preparation method
CN102727904A (en) * 2012-07-04 2012-10-17 广东大华农动物保健品股份有限公司 Heat resisting protective agent of bivalent live vaccine against highly pathogenic porcine reproductive and respiratory syndrome-pseudorabies and preparation method thereof
CN103007289A (en) * 2012-11-09 2013-04-03 上海创宏生物科技有限公司 Heat-resisting protective agent for duck virus hepatitis live vaccines and preparation method and application of protective agent
CN103285399A (en) * 2013-06-04 2013-09-11 中国食品药品检定研究院 Freezing and drying protecting agent for amyxis brucella live vaccine
CN103341176A (en) * 2013-07-03 2013-10-09 青岛易邦生物工程有限公司 Freeze-drying protective agent for vaccines
CN103341162A (en) * 2013-07-03 2013-10-09 青岛易邦生物工程有限公司 Freeze-dried vaccine of porcine transmissible gastroenteritis
CN103893776A (en) * 2014-03-18 2014-07-02 中国农业科学院兰州兽医研究所 Heat-resistant freezing and drying protecting agent for contagious ovine ecthyma virus cell attenuated vaccine as well as preparation method and application of heat-resistant freezing and drying protecting agent
CN104640566A (en) * 2012-08-21 2015-05-20 英特维特国际股份有限公司 Liquid stable virus vaccines
CN105497888A (en) * 2015-12-29 2016-04-20 瑞普(保定)生物药业有限公司 Heat-resisting protective agent live vaccine for Marek's disease of chicks and preparation method of live vaccine
CN105497904A (en) * 2015-12-22 2016-04-20 肇庆大华农生物药品有限公司 Heat-resistant freeze-drying protecting agent for pseudorabies virus vaccine and preparation method of heat-resistant freeze-drying protecting agent
CN108815517A (en) * 2018-07-13 2018-11-16 广东永顺生物制药股份有限公司 A kind of Duck plague live vaccine and preparation method thereof

Cited By (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100384993C (en) * 2005-11-02 2008-04-30 浙江大学 Process for increasing stability of elastase of lichen spore bacillus ZJUEL31410
CN100418580C (en) * 2005-11-14 2008-09-17 中国农业科学院哈尔滨兽医研究所 Heat resistant freeze drying protectant for chicken Newcastle disease live vaccine and its prepn and application
CN102397556A (en) * 2011-05-23 2012-04-04 上海创宏生物科技有限公司 Heatproof protection agent for live vaccine of duck viral hepatitis (DVH), preparation method thereof and application thereof
CN102294028A (en) * 2011-05-24 2011-12-28 南京创启生物科技有限公司 Chicken newcastle disease missing-resistant heat-resistant drinking water-immunization tablet and preparation method thereof
CN102430126A (en) * 2011-12-31 2012-05-02 山东滨州博莱威生物技术有限公司 Heat-resistant stabilizer for tissue fluid lyophilization, as well as preparation method and application thereof
CN102641504A (en) * 2012-04-14 2012-08-22 青岛农业大学 Heat-resistant freeze-drying protecting agent for vaccine and preparing method
CN102626520A (en) * 2012-04-23 2012-08-08 青岛农业大学 Heat-resisting cryoprotectant of mink canine distemper live vaccine and preparation method thereof
CN102671207B (en) * 2012-05-30 2013-06-05 青岛农业大学 Newcastle disease and avian infectious bronchitis bigeminal live vaccine heat-resisting freeze-drying protective agent and preparation method
CN102671207A (en) * 2012-05-30 2012-09-19 青岛农业大学 Newcastle disease and avian infectious bronchitis bigeminal live vaccine heat-resisting freeze-drying protective agent and preparation method
CN102671208A (en) * 2012-05-30 2012-09-19 青岛农业大学 Heat-resisting freeze-dried protective agent for live vaccine for chicken infectious bursal diseases and preparation method for heat-resisting freeze-dried protective agent
CN102671209A (en) * 2012-05-30 2012-09-19 青岛农业大学 Heat-resistant freeze-drying protective agent for newcastle disease live vaccines and preparation method
CN102671208B (en) * 2012-05-30 2013-07-03 青岛农业大学 Heat-resisting freeze-dried protective agent for live vaccine for chicken infectious bursal diseases and preparation method for heat-resisting freeze-dried protective agent
CN102727904B (en) * 2012-07-04 2013-08-28 广东大华农动物保健品股份有限公司 Heat resisting protective agent of bivalent live vaccine against highly pathogenic porcine reproductive and respiratory syndrome-pseudorabies and preparation method thereof
CN102727904A (en) * 2012-07-04 2012-10-17 广东大华农动物保健品股份有限公司 Heat resisting protective agent of bivalent live vaccine against highly pathogenic porcine reproductive and respiratory syndrome-pseudorabies and preparation method thereof
CN104640566B (en) * 2012-08-21 2021-08-06 英特维特国际股份有限公司 Liquid stable viral vaccines
CN104640566A (en) * 2012-08-21 2015-05-20 英特维特国际股份有限公司 Liquid stable virus vaccines
CN103007289B (en) * 2012-11-09 2014-04-23 上海创宏生物科技有限公司 Heat-resisting protective agent for duck virus hepatitis live vaccines and preparation method and application of protective agent
CN103007289A (en) * 2012-11-09 2013-04-03 上海创宏生物科技有限公司 Heat-resisting protective agent for duck virus hepatitis live vaccines and preparation method and application of protective agent
CN103285399A (en) * 2013-06-04 2013-09-11 中国食品药品检定研究院 Freezing and drying protecting agent for amyxis brucella live vaccine
CN103341176A (en) * 2013-07-03 2013-10-09 青岛易邦生物工程有限公司 Freeze-drying protective agent for vaccines
CN103341162A (en) * 2013-07-03 2013-10-09 青岛易邦生物工程有限公司 Freeze-dried vaccine of porcine transmissible gastroenteritis
CN103341176B (en) * 2013-07-03 2015-06-10 青岛易邦生物工程有限公司 Freeze-drying protective agent for vaccines
CN103893776A (en) * 2014-03-18 2014-07-02 中国农业科学院兰州兽医研究所 Heat-resistant freezing and drying protecting agent for contagious ovine ecthyma virus cell attenuated vaccine as well as preparation method and application of heat-resistant freezing and drying protecting agent
CN103893776B (en) * 2014-03-18 2016-04-06 中国农业科学院兰州兽医研究所 Sheep infective pustule virus cell weak-toxic vaccine heat-resisting lyophilized protecting agent and its preparation method and application
CN105497904A (en) * 2015-12-22 2016-04-20 肇庆大华农生物药品有限公司 Heat-resistant freeze-drying protecting agent for pseudorabies virus vaccine and preparation method of heat-resistant freeze-drying protecting agent
CN105497888A (en) * 2015-12-29 2016-04-20 瑞普(保定)生物药业有限公司 Heat-resisting protective agent live vaccine for Marek's disease of chicks and preparation method of live vaccine
CN108815517A (en) * 2018-07-13 2018-11-16 广东永顺生物制药股份有限公司 A kind of Duck plague live vaccine and preparation method thereof
CN108815517B (en) * 2018-07-13 2021-09-14 广东永顺生物制药股份有限公司 Duck plague live vaccine and preparation method thereof

Also Published As

Publication number Publication date
CN1168503C (en) 2004-09-29

Similar Documents

Publication Publication Date Title
CN1426816A (en) Veterinarian virus kind biological product heat resisting freeze drying protective agent and its preparation technique
Rauw et al. Improved vaccination against Newcastle disease by an in ovo recombinant HVT-ND combined with an adjuvanted live vaccine at day-old
JP5537429B2 (en) Method for producing influenza virus
US20100003279A1 (en) Vaccine for in ovo inoculation
CN101947321A (en) Heat-resisting and freeze-drying protector for live vaccine and preparation method thereof as well as live newcastle disease vaccine
CN1233418C (en) Heat-resisting lyophilized protectant for chicken newcastle disease, chicken infectious bronchitis (H120, H52) dual lyophilized vaccine and preparing process thereof
CN1146443C (en) In oVO vaccination against newcastle disease
Li et al. A highly pathogenic Marek’s disease virus isolate from chickens immunized with a bivalent vaccine in China
CN1063971C (en) Method for preparing freeze-dried live vaccine for animal use
Dilaveris et al. The safety and immunogenicity of an in ovo vaccine against Newcastle disease virus differ between two lines of chicken
CN1222314C (en) Heat resisting lyophilized protectant for chicken Marek's disense turkey herpes virus lyophilized vaccine and preparing process thereof
CN1251762C (en) Heat resisting lyophilized protectant for chicken infections Fabianite bursa hypotpxicity (B87) lyophilized vaccine and preparing process thereof
CN102309759B (en) Poultry freeze-drying live vaccine heat-resisting protective agent and preparation method thereof
CN1253209C (en) Heat-resistant lyophilized protectant of lyophilized vaccine for henpox and preparing process thereof
CN1223375C (en) Heat resisting lyophilized protectant for chicken infectious bronchitis (H120, H52, Kidney infectious bronchitis W93) lyophilized vaccine and preparing process thereof
CN1222320C (en) Heat-resistant lyophilized protectant of lyophilized vaccine for chicken infectious laryngotracheitis and preparing process thereof
Waziri et al. Cuteneous and diphtheritic forms of avian pox infections in a juvenile ostrich
BehrouziNasab Comparative Study of Vaccine-Induced Humoral Immune Response against Newcastle Disease Virus and Avian Influenza Virus (H9N2) in Different Bird Species of Mashhad Birds Garden
Rajab et al. Comparison of HVT-ND recombinant and convection-based Newcastle disease vaccination programs in the protection against the genotype VII NDV challenges: an experimental study
RU2195959C1 (en) Inactivated vaccine against hens' hydropericarditis syndrome
RU2304447C1 (en) Culture vaccine against poultry pox out of hen's virus (ospovac) (variants)
RU2205660C2 (en) Virus vaccine against marek's disease
Soltani et al. The simultaneous presence of three different Newcastle Disease Virus Genotypes in various bird species in a public bird garden
RU2199342C1 (en) Method for preparing inactivated vaccine against hen's hydropericarditis syndrome
RU2403060C2 (en) Method of newcastle disease prevention

Legal Events

Date Code Title Description
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
C19 Lapse of patent right due to non-payment of the annual fee
CF01 Termination of patent right due to non-payment of annual fee