CN106668867B - A kind of mumps vaccine freeze drying protectant without gelatin and human serum albumin - Google Patents
A kind of mumps vaccine freeze drying protectant without gelatin and human serum albumin Download PDFInfo
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5254—Virus avirulent or attenuated
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/18011—Paramyxoviridae
- C12N2760/18111—Avulavirus, e.g. Newcastle disease virus
- C12N2760/18134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
Abstract
The present invention relates to field of biological product, and in particular to a kind of mumps vaccine freeze drying protectant without gelatin and human serum albumin.Its each ingredient of freeze drying protectant of the invention is final concentration of in mumps vaccine semi-finished product: sucrose 30-100g/L, sodium glutamate 0.5-15g/L, urea 0-10g/L, disodium hydrogen phosphate 1-20g/L, citric acid 0.2-10g/L; preparing protectant matrix liquid is 199 culture solutions or PBS buffer solution or water for injection; and gelatin and human serum albumins are free of in the freeze drying protectant, the vaccine semi-finished product refer to the liquid vaccine before freeze-drying.The present invention also provides the purposes of the freeze drying protectant.When the freeze drying protectant is used to prepare freeze dried vaccine, stability of vaccine during freeze-drying process and storage can be improved, and greatly improve safety of the freeze dried vaccine to human body, reduce the adverse reaction of vaccine.
Description
Technical field
The present invention relates to field of biological product, and in particular to a kind of to protect without the mumps vaccine of gelatin and human serum albumin
Protect the formula and application method of agent.
Background technique
The application of preventative vaccine makes common epidemic infectious diseases obtain effective control, effectively reduces these infections
The morbidity and mortality of disease.But find that most of vaccines have higher adverse reaction in the use process of vaccine
Incidence；Extensive use with vaccine and the further investigation discovery to adverse reaction inducement, occur after many vaccine inoculations
The protective agent of adverse reaction problem and vaccine product has the freeze drying protectant in direct relation, especially freeze dried vaccine product,
In gelatin or gelatine derivative can directly cause the allergy such as vaccinee's allergy, research shows that the mistake of human body caused by gelatin
Quick reaction has humoral immune mechanisms (IgE antibody), and also having cellular immune mechanism, (Zhang Zhuoguang, the sensitization of ox source gelatin is made in vaccine
With " foreign medical science ", (the 2nd phase) in 2002,25).
Existing vaccine product majority is that the biological products regulation issued with reference to the World Health Organization is standard production, mark
Protectant gelatin usage amount is not limited in standard.Japanese FDA in 1986 approval vaccine listing license and
In the vaccine listing license of U.S. FDA approval, not using gelatin as the disabling ingredient of production vaccine.In the patent text of early stage
In offering, most of vaccine protectants all contain gelatin.
Chinese Pharmacopoeia Commission is distinctly claimed in 5 Beijing Meeting summary on July 17th, 2007 to July 19 " as stabilization
After being injected into human body allergic reaction can occur for the gelatin of agent ingredient, and manufacturing enterprise should carry out the correlative study work for replacing gelatin
Make, to further increase the safety of product ".
Currently, human serum albumins is widely used Virus culture and freeze drying protectant in vaccines arts, human seralbumin egg
White extracted from the blood plasma of people, and such production method is not only limited by blood plasma supply, but also may be contained dangerous
Infectious disease pathogens, such as hepatitis virus etc., therefore there are biggish worries in use process；In addition, human serum albumins
It is expensive so that the cost of vaccine rises sharply.So a series of substitute for forcing researcher to study human serum albumins is come
Improve traditional formula.
Although protective agent without gelatin, human serum albumins in currently available technology reduces the irritation to human body,
But it is unsatisfactory to the protecting effect of vaccine, so that stability decline of the vaccine in freeze-drying process and during storage, easily
It fails.Therefore, it is badly in need of a kind of safely and effectively gelatin-free in this field, without human serum albumins vaccine freeze-drying protective agent,
While ensureing vaccine quality, immune risk and production cost are reduced.
Summary of the invention
The object of the present invention is to provide a kind of new generation vaccine freeze drying protectants without gelatin, without human serum albumin, make
Endotoxin content decline, is not susceptible to allergic reaction, and be still able to maintain higher stability and longer validity period.
In order to achieve the above object, the present invention provides a kind of vaccine freeze-drying protective agent, and each ingredient of the freeze drying protectant is in epidemic disease
It is final concentration of in seedling semi-finished product: sucrose 30-100g/L, sodium glutamate 0.5-15g/L, urea 0-10g/L, disodium hydrogen phosphate 1-
20g/L, citric acid 0.2-10g/L；The vaccine semi-finished product refer to the liquid vaccine before freeze-drying.
Preferably, each ingredient of the freeze drying protectant is final concentration of in vaccine semi-finished product: sucrose 30-80g/L, glutamic acid
Sodium 0.5-10g/L, urea 0-5g/L, disodium hydrogen phosphate 1-10g/L, citric acid 0.2-5g/L.
It is highly preferred that each ingredient of the freeze drying protectant is final concentration of in vaccine semi-finished product: sucrose 50g/L, glutamic acid
Sodium 10g/L, urea 5g/L, disodium hydrogen phosphate 10g/L, citric acid 5g/L.
Mumps vaccine freeze drying protectant provided by the invention is free of gelatin and human serum albumin in ingredient.
Matrix liquid for preparing freeze drying protectant of the present invention is 199 culture solutions or PBS buffer solution or water for injection.
Further, 199 culture solutions are without phenol red 199 culture medium.
The present invention provides application of the above-mentioned mumps vaccine freeze drying protectant in preparation freeze-drying mumps vaccine.
Further, the present invention provides a kind of methods for preparing freeze-drying mumps vaccine, comprising the following steps:
Mumps virus liquid is provided；
Mumps vaccine freeze drying protectant of the present invention is proportionally added into virus liquid, it is living that mumps virus is made
Vaccinogen liquid；
By live mumps virus vaccine stoste by target viral titre in vaccine semi-finished product be added appropriate diluent preparing at
Vaccine semi-finished product keep each ingredient in vaccine freeze-drying protective agent final concentration of in vaccine semi-finished product: sucrose 30-100g/L, paddy
Propylhomoserin sodium 0.5-15g/L, urea 0-10g/L, disodium hydrogen phosphate 1-20g/L, citric acid 0.2-10g/L；The dilution contains
Ingredient identical with freeze drying protectant of the invention, and the concentration of each ingredient and freeze drying protectant of the present invention are in vaccine semi-finished product
Final concentration it is consistent；The vaccine semi-finished product are the liquid vaccine before freeze-drying；The target viral titre is 5.8 ± 0.3lg
CCID50/ml；
Vaccine semi-finished product dispense under the conditions of 2-8 DEG C, freeze-drying.
The condition of freeze-drying are as follows: -45 DEG C~-48 DEG C of pre-freeze stage minimum temperature maintains 2 hours after reaching minimum temperature；It rises
Magnificent -35 DEG C of drying stage final temperature, the time for reaching final temperature is 17 hours, and vacuum pressure is controlled in 4-6Pa；Solution blots
28 DEG C of dry stage final temperature, vacuum does not control, and runs 8 hours.
The present invention is also belonged to using a kind of freeze-drying mumps vaccine that above-mentioned preparation method provided by the invention is prepared
Protection scope.
A kind of freeze drying protectant the present invention provides gelatin-free without human serum albumin, being capable of reasonable replacing gelatin and people
Blood albumin, and the identical validity of similar product can be reached, and there is higher safety.Freeze drying protectant in the present invention
Safety and the less susceptible generation allergic reaction of commercialized product, safety is higher, and the quality of vaccine is much higher than " Chinese Pharmacopoeia "
Three required standards, effect include:
(1) gelatin, human serum albumin, dextran, trehalose are not contained in protective agent ingredient, are not easy to cause allergy anti-
It answers, such as nettle rash, pruitus, fever, nausea, the safety of vaccine is higher, reduces the adverse reaction of vaccine inoculation；
(2) 4.8lgCCID is all larger than using Mumps Vaccine,Live finished product virus titer prepared by the present invention50/ ml, matter
Amount standard is higher than " Chinese Pharmacopoeia " three requirements and is not less than 4.0lgCCID50/ ml standard；Heat stabilization test result is all larger than
4.4lgCCID50/ ml, quality standard are higher than " Chinese Pharmacopoeia " three requirements and are not less than 4.0lgCCID50/ ml standard；Virus titer
Drop-out value is not higher than 0.6lg, and quality standard is higher than " Chinese Pharmacopoeia " three requirement declines and is not higher than 1.0lg standard；
(3) moisture is below 2.0%, and it is of less demanding in 3.0% standard that quality standard is higher than " Chinese Pharmacopoeia " three；
(4) not low using Mumps Vaccine,Live finished product accelerated stability prepared by the present invention and long-time stability result
In the control sample containing gelatin and human serum albumin；
(5) using Mumps Vaccine,Live finished product prepared by the present invention endotoxin content well below 2015 editions " in
State's pharmacopeia " three require (50EU/ agent should be not higher than)；
(6) Mumps Vaccine,Live finished product carries out cavy whole body active hypersensitive test: test sample subcutaneous injection sensitization
Intravenous administration excites again afterwards, and generated systemic anaphylaxis after observation cavy injection test sample, allergic reaction should be negative.
Specific embodiment
Following embodiment further illustrates the contents of the present invention, but should not be construed as limiting the invention.Without departing substantially from
In the case where spirit of that invention and essence, to modifications or substitutions made by the method for the present invention, step or condition, the present invention is belonged to
Range.
Unless otherwise specified, the conventional means that technological means used in embodiment is well known to those skilled in the art；
Unless otherwise specified, agents useful for same is commercially available in embodiment.Mumps virus S79Strain derives from Ministry of Public Health Shanghai biological products
Research institute.
Mumps virus S in 1 embodiment of the present invention of embodiment79The preparation method of strain virus liquid
1. the SPF hatching egg hatched 9~11 days is dissected, chicken embryo head and internal organ are discarded, tissue block digestion preparation is thin
Cell suspension is diluted to suitable cell concentration with cell nutrient solution by born of the same parents' suspension, is sub-packed in 10L rolling bottle and is placed in 36.5 ± 1 DEG C
Thermostatic chamber culture, culture is to growing up to fine and close cell monolayer.
2. abandoning cell nutrient solution after cell grows up to fine and close single layer and changing 7.2~7.4 viral growth liquid of pH value, press
MOI0.001~0.01 is inoculated with mumps virus (S79Strain), it is placed in 33 ± 1 DEG C of thermostatic chambers and continues to cultivate.
3. Virus culture discards viral growth liquid after 44~52 hours, and with 0.85% brine cell surface
Bovine serum albumin(BSA) is removed, the viral maintaining liquid without bovine serum albumin(BSA), pH value 7.4~7.6 is added after washing, it is placed in 33 ±
Continue to cultivate in 1 DEG C.
It is single harvest liquid after merging 4. microscopic observation when lesion reaches 75% or more, harvests virus liquid.
Component, the content (final concentration in vaccine semi-finished product) of the freeze drying protectant of the present invention of embodiment 2
Component 1: sucrose, pharmaceutical grade, 30~100g/L；
Component 2: sodium glutamate, pharmaceutical grade, 0.5~15g/L；
Component 3: urea, pharmaceutical grade, 0.0~5.0g/L；
Component 4: disodium hydrogen phosphate analyzes pure, 1.0~20g/L；
Component 5: citric acid, pharmaceutical grade, 0.2~10g/L；
Solvent: water for injection or PBS buffer solution or 199 culture solutions；
The preparation method of freeze drying protectant of the present invention:
(1) after weighing said components 1, solvent dissolution, fixed molten laggard horizontal high voltage steam sterilizing is added, sterilising conditions are
121 DEG C, 30 minutes；
(2) said components 2, component 3 are weighed, solvent dissolution is added, fixed molten rear liquid passes through 0.2 micron membrane filter degerming
Filter, is placed in 2~8 DEG C of freezers, spare；
(3) said components 4, component 5 are weighed, solvent dissolution is separately added into, then mixing is fixed molten, and fixed molten rear liquid passes through
0.2 micron membrane filter aseptic filtration is placed in 2~8 DEG C of freezers, spare；
(4) protective agent is mixed (1) (2) (3) using preceding.
Embodiment 3
With mumps virus S79The work seed of strain preparation is inoculated with primary chick embryo cell, will after being cultivated, harvesting virus liquid
Freeze drying protectant and virus harvest liquid are mixed with vaccinogen liquid in the ratio of 1:4 (V/V), wherein freeze drying protectant is in vaccine
Final concentration of sucrose 50g/L, sodium glutamate 10g/L, urea 5g/L, disodium hydrogen phosphate 10g/L, citric acid 5g/L in stoste.
The dilution of appropriate pH6.8~7.0 is added into vaccinogen liquid, so that target viral titre is 5.8lgCCID50/
Ml, i.e. acquisition semi-finished product solution；Wherein, dilution is to contain sucrose 50g/L, sodium glutamate 10g/L, urea 5g/L, phosphoric acid hydrogen
The solution of disodium 10g/L, citric acid 5g/L.
Semi-finished product are sub-packed in cillin bottle and are lyophilized, as Mumps Vaccine,Live finished product.
Freeze drying process are as follows: -45 DEG C of pre-freeze phase temperature maintains 2 hours after reaching temperature；Lyophilization stage most final temperature
- 35 DEG C of degree, the time for reaching final temperature is 17 hours, and vacuum pressure is controlled in 5 ± 1Pa；Desorbing and drying stage final temperature
28 DEG C, vacuum does not control, and runs 8 hours.
Embodiment 4
With mumps virus S79The work seed of strain preparation is inoculated with primary chick embryo cell, will after being cultivated, harvesting virus liquid
Freeze drying protectant and virus harvest liquid are mixed with vaccinogen liquid in the ratio of 1:4 (V/V), wherein freeze drying protectant is in vaccine
Final concentration of sucrose 30g/L, sodium glutamate 3g/L, urea 2g/L, disodium hydrogen phosphate 5g/L, citric acid 2g/L in stoste.
The dilution of appropriate pH6.8~7.0 is added into vaccinogen liquid, so that target viral titre is 5.8lg CCID50/
Ml, i.e. acquisition semi-finished product solution；Wherein, dilution is to contain sucrose 30g/L, sodium glutamate 3g/L, urea 2g/L, phosphoric acid hydrogen two
The solution of sodium 5g/L, citric acid 2g/L.
Semi-finished product are sub-packed in cillin bottle and are lyophilized, as Mumps Vaccine,Live finished product.
Freeze drying process are as follows: -45 DEG C of pre-freeze phase temperature maintains 2 hours after reaching temperature；Lyophilization stage most final temperature
- 35 DEG C of degree, the time for reaching final temperature is 17 hours, and vacuum pressure is controlled in 5 ± 1Pa；Desorbing and drying stage final temperature
28 DEG C, vacuum does not control, and runs 8 hours.
Embodiment 5
With mumps virus S79The work seed of strain preparation is inoculated with primary chick embryo cell, will after being cultivated, harvesting virus liquid
Freeze drying protectant and virus harvest liquid are mixed with vaccinogen liquid in the ratio of 1:4 (V/V), wherein freeze drying protectant is in vaccine
Final concentration of sucrose 80g/L, sodium glutamate 2g/L, disodium hydrogen phosphate 3g/L, citric acid 0.2g/L in stoste.
The dilution of appropriate pH6.8~7.0 is added into vaccinogen liquid, so that target viral titre is 5.8lgCCID50/
Ml, i.e. acquisition semi-finished product solution；Wherein, dilution is to contain sucrose 80g/L, sodium glutamate 2g/L, disodium hydrogen phosphate 3g/L, Chinese holly
The solution of rafter acid 0.2g/L.
Semi-finished product are sub-packed in cillin bottle, are lyophilized, as Mumps Vaccine,Live finished product.
Freeze drying process are as follows: -45 DEG C of pre-freeze phase temperature maintains 2 hours after reaching temperature；Lyophilization stage most final temperature
- 35 DEG C of degree, the time for reaching final temperature is 17 hours, and vacuum pressure is controlled in 5 ± 1Pa；Desorbing and drying stage final temperature
28 DEG C, vacuum does not control, and runs 8 hours.
To Mumps Vaccine,Live finished product made from above 3~5 embodiment respectively at 37 DEG C, 4 DEG C of placement different times,
Sampling carries out appearance, moisture and titration of virus, and (contains gelatin with the commercialized product of emerging (Dalian) Vaccine Technology Co., Ltd, section
And human serum albumins) Mumps Vaccine,Live product compare.
Quality standard is as follows:
(1) appearance: faint yellow loosening body is weak yellow liquid, foreign after redissolution.
(2) moisture: checking according to the Pharmacopoeia of the People's Republic of China three (Ⅻ D of annex), should be not higher than 3.0%.
(3) titration of virus detection titration of virus: is carried out using Microdose cytopathic effect assay.3 bottles of vaccine mixing are taken, it is appropriate to carry out
Dilution, every dilution virus liquid connect Vero cell, set 36.5 ± 1 DEG C, 5%CO2Culture is cultivated 8 days and is determined as a result, virus titer
4.0lg CCID should be not less than50/ml.It the results are shown in Table 1, table 2.
Table 1 Mumps Vaccine,Live, 37 DEG C of accelerated stability results
※The Mumps Vaccine,Live batch number listed for emerging (Dalian) Vaccine Technology Co., Ltd, section.
Table 2 Mumps Vaccine,Live, 2~8 DEG C of long-time stability results
※The Mumps Vaccine,Live batch number listed for emerging (Dalian) Vaccine Technology Co., Ltd, section.
To the finished product of the protective agent of above 3~5 embodiment production respectively at carrying out safety evaluatio, and it is emerging (Dalian) with section
The Mumps Vaccine,Live product of the commercialized product (containing gelatin and human serum albumins) of Vaccine Technology Co., Ltd carries out
Comparison.
Evaluation criterion is as follows:
(1) it baterial endotoxin test: is examined according to the Pharmacopoeia of the People's Republic of China three (Ⅻ E gel limiting test of annex)
It looks into, 50EU/ agent should be not higher than.
(2) cavy whole body active hypersensitive test: intravenous administration excites again after test sample subcutaneous injection sensitization, observes globefish
Mouse injects generated systemic anaphylaxis after test sample, and allergic reaction should be negative.Test result such as the following table 3:
3 Mumps Vaccine,Live safety evaluatio of table
| Embodiment | Baterial endotoxin test | Cavy whole body active hypersensitive test |
| 3 | <1.25 | It is negative |
| 4 | <1.25 | It is negative |
| 5 | <1.25 | It is negative |
| 201210003※ | <12.5 | It is negative |
※The Mumps Vaccine,Live batch number listed for emerging (Dalian) Vaccine Technology Co., Ltd, section
As can be seen from the above data, it is of the invention without gelatin and human serum albumin protective agent with it is current conventional use of
It is compared containing gelatin with human serum albumin protective agent, there was no significant difference for stability result, but vaccine freeze-drying protection of the invention
Agent improves the safety of vaccine, can reduce the adverse reaction of vaccine.
Although above having used general explanation, specific embodiment and test, the present invention is made to retouch in detail
It states, but on the basis of the present invention, it can be made some modifications or improvements, this is apparent to those skilled in the art
's.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, belong to claimed
Range.
Claims (9)
1. a kind of mumps vaccine freeze drying protectant, which is characterized in that each ingredient of the freeze drying protectant is in vaccine semi-finished product
It is final concentration of: sucrose 30-80 g/L, sodium glutamate 0.5-10 g/L, urea 0-5 g/L, disodium hydrogen phosphate 1-10 g/L, citron
Sour 0.2-5 g/L；The vaccine semi-finished product refer to the liquid vaccine before freeze-drying.
2. mumps vaccine freeze drying protectant as described in claim 1, which is characterized in that each ingredient of the freeze drying protectant is in epidemic disease
It is final concentration of in seedling semi-finished product: sucrose 50g/L, 10 g/L of sodium glutamate, 5 g/L of urea, 10 g/L of disodium hydrogen phosphate, citron
5 g/L of acid.
3. the mumps vaccine freeze drying protectant as described in claim 1-2 is any, which is characterized in that white without gelatin and people's blood
Albumen.
4. the mumps vaccine freeze drying protectant as described in claim 1-2 is any, which is characterized in that prepare protectant matrix
Liquid is 199 culture solutions or PBS buffer solution or water for injection.
5. mumps vaccine freeze drying protectant as claimed in claim 4, which is characterized in that 199 culture solutions are no phenol
Red 199 culture medium.
6. the described in any item mumps vaccine freeze drying protectants of claim 1-5 answering in preparation freeze-drying mumps vaccine
With.
7. application as claimed in claim 6, it is characterised in that: the following steps are included:
Mumps virus liquid is provided；
The described in any item mumps vaccine freeze drying protectants of claim 1-5 are proportionally added into virus liquid, the parotid gland is made
Scorching viral lived vaccine stoste；
Appropriate diluent preparing is added into vaccine by target viral titre in vaccine semi-finished product in live mumps virus vaccine stoste
Semi-finished product；The dilution contains the freeze drying protectant, the concentration of each ingredient of freeze drying protectant and its vaccine half at
Final concentration in product is consistent；The vaccine semi-finished product are the liquid vaccine before freeze-drying；The target viral titre be 5.8 ±
0.3lg CCID50/ml；
Vaccine semi-finished product dispense under the conditions of 2-8 DEG C, freeze-drying.
8. according to any application of claim 6-7, the condition of freeze-drying are as follows: -45 DEG C ~ -48 DEG C of pre-freeze stage minimum temperature,
It is maintained 2 hours after reaching minimum temperature；- 35 DEG C of final temperature of the lyophilization stage, the time for reaching final temperature is 17 hours,
Vacuum pressure is controlled in 4-6Pa；28 DEG C of parsing-desiccation stage final temperature, vacuum does not control, and runs 8 hours.
9. the vaccine freeze-drying product that any application of claim 7-8 is prepared.
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| CN110101864A (en) * | 2019-05-31 | 2019-08-09 | 辽宁茂康源生物科技有限公司 | The protective agent of serum-free Antirabic Vaccine a kind of and its application |
| CN113144209A (en) * | 2021-01-19 | 2021-07-23 | 上海荣盛生物药业有限公司 | Rabies vaccine freeze-drying protective agent |
| CN115105604A (en) * | 2022-07-05 | 2022-09-27 | 吉林惠康生物药业有限公司 | Vaccine freeze-drying protective agent and freeze-drying method thereof |
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