CN1262131A

CN1262131A - Microbe protection with trehalose instead of human serum albumin and microbe preparation

Info

Publication number: CN1262131A
Application number: CN 99100443
Authority: CN
Inventors: 张晶; 赵军; 李莹; 胡晓晨; 董义兰; 王德贤; 赵克俭; 高俊芳; 赵伟光; 贾国富
Original assignee: CHANGCHUN CHANGSHENG INDUSTRY Co Ltd
Current assignee: CHANGCHUN CHANGSHENG INDUSTRY Co Ltd
Priority date: 1999-01-29
Filing date: 1999-01-29
Publication date: 2000-08-09

Abstract

A trehalose is used as a new protector of biologic preparation (vaccine and gene engineering products). It can replace the human serum albmin which is originally used as said protector but has the disadvantages of less raw materials, high cost and potential pollution from external factor. Its advantages are high safety, low cost, high protection effect and stability, no poison and harm, and no untoward effect.

Description

Protection with trehalose instead of human serum albumin microorganism and microorganism formulation

The prior art situation:

At present, the vaccine of domestic production, recombinant product etc. all end user's blood albumin as protective agent, and produce the human albumin the raw material sources difficulty, cost an arm and a leg, and potential exogenous factor pollutes.Patent of the present invention adopts this protective agent of trehalose to substitute the human albumin and protects microorganism and microorganism formulation, both can reduce the cost of microorganism formulation, guarantees safe and effectively, and its stability also has raising.

Basic technology:

1. the Hepatitis A Vaccine liquid results back as the preparation of the protective agent conventional method of attenuated hepatitis A live vaccine adds trehalose liquid, and making its final concentration is 1-5%.Advantage: make the vaccine protective agent with trehalose instead of human serum albumin, can make vaccine be easy to preserve, good stability has thoroughly solved the liquid preparation hepatitis A and has subtracted problems such as the cold chain transportation of duty live vaccine and poor stability.(it is 12 months that the people does protectant hepatitis A vaccine-20 ℃ effect phase in vain, and 2-8 ℃ of 3 months effect phase).2-8 ℃ of goods effect duration can be done in vain to extend to 12 months (trehalose) in protectant 3 months from the people.Example: make protectant liquid hepatitis A vaccine accelerated stability test result with trehalose; 37 ℃ 7 days, the front and back virus titer descends and to be no more than 0.5LogTCID ₅₀/ mL37 ℃ 15 days, the front and back virus titer descends and to be no more than 0.5LogTCID ₅₀/ mL; 2-8 ℃ 12 months, virus titer descends and to be no more than 0.5LogTCID ₅₀/ mL; As genetic engineering interferon (α. β. γ), the protective agent of interleukin one II; add trehalose, dextran among genetic engineering interferon, the Bai Jieqin; make its final concentration be respectively 0.5-3%; 0.5-2%; pack into after the mixing and carry out lyophilization, moisture content≤3% (g/g) advantage in the medical freezing case: use trehalose instead of human serum albumin, cost reduces; and the stability of goods is reserved, and is easy to preserve.Example; Make protectant interferon with trehalose, 37 ℃ 6 months its tire and stable do not fall.3. substitute the human albumin and make cryodesiccant live measles vaccine; the protective agent of lyophilizing Mumps Vaccine; the live measles vaccine of results, Freeae Dried Parotits Vaccine Live add freeze drying protectant according to 4: 1 ratio; protective agent ultimate density in the live measles vaccine of results is respectively 1-5% trehalose, 0.5-0.9% gelatin, 3-6% sucrose, 0.5-2% monosodium glutamate, 0.3-0.8% carbamide and 0.1-0.4%L-arginine; pack into after the mixing and carry out lyophilization in the medical freezing case; pre-freeze is 5 hours promptly-45 ℃; begin to heat up; control is warm at 30 ℃, 6 hours.Goods are faint yellow loose body moisture content≤3% (g/g) after the lyophilizing: example: the measles after the lyophilizing subtracts the duty live vaccine, Freeae Dried Parotits Vaccine Live accelerated stability test result: 37 ℃ 7 days, the front and back titre not super 0.5LogCCID that descends ₅₀/ mL:37 ℃ 14 days, the front and back titre descends and to be no more than 0.5LogCCID ₅₀/ mL; 2-8 ℃ of 18 months virus titer descends and is no more than 1.0LogCCID ₅₀/ mL; 4. substitute the protective agent that the human albumin makes refining rabies vaccine.The trehalose that adds final concentration in the refining rabies vaccine of results and be 1-5% is made protective agent, both can reduce cost, and can make vaccine obtain better protect again, and it is stable to tire.Example: 37 ℃ 7 days, vaccine valence basicly stable constant (〉=2.5IU/ dosage); 37 ℃ of 28 no vaccine valence fall little (〉=2.5IU/ dosage); 2-8 ℃ 12 months, vaccine valence is stablized (〉=2.5IU/ dosage); 2-8 ℃ 15 months, vaccine valence is stablized (〉=2.5IU/ dosage); 2-8 ℃ 18 months, vaccine valence slightly descend (〉=2.5IU/ dosage);

Claims

1. a Bioprotective-trehalose is used for substituting the human albumin and protects microorganism and microorganism formulation, the white crystals body that trehalose system extracts from discarded enzyme mother.

2. the trehalose instead of human serum albumin of telling about according to claim 1, as the protective agent of attenuated hepatitis A live vaccine, this vaccine can be preserved 1 year and virus titer does not descend in 2-8 ℃.The concentration of trehalose is 1-5%.

3. trehalose instead of human serum albumin according to claim 1 as genetic engineering interferon (α. β. the γ) protective agent of interleukin-II; add trehalose, dextran in the goods; make its concentration be respectively 0.5-3%, 0.5-2%; mix postlyophilization; do back moisture content≤3% (g/g), tiring of goods is stable.

4. trehalose instead of human serum albumin according to claim 1 is as cryodesiccant live measles vaccine; the protective agent of freeze dried mumps vaccine,live; adding freeze drying protectant (by the volume ratio of 4:1) protective agent in the vaccine liquid of results is respectively in the vaccine ultimate density: trehalose 1-5%; gelatin 0.5-0.9%, sucrose 3-6%, monosodium glutamate 0.5-2%; carbamide 0.3-0.8%; L-arginine 0.1-0.4% mixes postlyophilization, dry back goods moisture≤3% (g/g).

5. trehalose according to claim 1 is as the freeze drying protectant of thymosin, and the trehalose final concentration is 0.5-3% in the thymosin, mixes postlyophilization, dry back moisture≤3% (g/g); The thymosin activity is protected.

6. trehalose instead people Bai Zuowei according to claim 1 makes with extra care the rabies vaccine protective agent, and the trehalose final concentration is 0.5-3% in the vaccine, and this vaccine can be tired stable in 2-8 ℃ of preservation 1 year.