CN116370620A - Composite water-soluble adjuvant with small stress for producing vaccine and preparation method thereof - Google Patents
Composite water-soluble adjuvant with small stress for producing vaccine and preparation method thereof Download PDFInfo
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- CN116370620A CN116370620A CN202310564030.4A CN202310564030A CN116370620A CN 116370620 A CN116370620 A CN 116370620A CN 202310564030 A CN202310564030 A CN 202310564030A CN 116370620 A CN116370620 A CN 116370620A
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- 229960005486 vaccine Drugs 0.000 title claims abstract description 65
- 239000002131 composite material Substances 0.000 title claims abstract description 36
- 238000002360 preparation method Methods 0.000 title description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 24
- 230000000091 immunopotentiator Effects 0.000 claims abstract description 24
- 229920000642 polymer Polymers 0.000 claims abstract description 24
- 150000001875 compounds Chemical class 0.000 claims abstract description 19
- 239000012752 auxiliary agent Substances 0.000 claims abstract description 15
- 229920002521 macromolecule Polymers 0.000 claims abstract description 14
- 239000008215 water for injection Substances 0.000 claims abstract description 10
- 239000004475 Arginine Substances 0.000 claims description 21
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 21
- 235000009697 arginine Nutrition 0.000 claims description 21
- -1 sorbitol fatty acid ester Chemical class 0.000 claims description 21
- DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 20
- 239000001397 quillaja saponaria molina bark Substances 0.000 claims description 18
- 229930182490 saponin Natural products 0.000 claims description 18
- 150000007949 saponins Chemical class 0.000 claims description 18
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 17
- 239000000194 fatty acid Substances 0.000 claims description 17
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- 239000007864 aqueous solution Substances 0.000 claims description 16
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 13
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- 238000004090 dissolution Methods 0.000 claims description 10
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- 235000011187 glycerol Nutrition 0.000 claims description 7
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 6
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims description 6
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- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims description 6
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- 229930064664 L-arginine Natural products 0.000 claims description 5
- 235000014852 L-arginine Nutrition 0.000 claims description 5
- 125000002059 L-arginyl group Chemical class O=C([*])[C@](N([H])[H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])C(=N[H])N([H])[H] 0.000 claims description 5
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- JDRSMPFHFNXQRB-CMTNHCDUSA-N Decyl beta-D-threo-hexopyranoside Chemical compound CCCCCCCCCCO[C@@H]1O[C@H](CO)C(O)[C@H](O)C1O JDRSMPFHFNXQRB-CMTNHCDUSA-N 0.000 claims description 4
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- 229940073499 decyl glucoside Drugs 0.000 claims description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 4
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 4
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 4
- 229920000193 polymethacrylate Polymers 0.000 claims description 4
- 235000013772 propylene glycol Nutrition 0.000 claims description 4
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims description 4
- 239000000600 sorbitol Substances 0.000 claims description 4
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- 235000021314 Palmitic acid Nutrition 0.000 claims description 3
- 229930006000 Sucrose Natural products 0.000 claims description 3
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 claims description 3
- PYIDGJJWBIBVIA-UYTYNIKBSA-N lauryl glucoside Chemical compound CCCCCCCCCCCCO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O PYIDGJJWBIBVIA-UYTYNIKBSA-N 0.000 claims description 3
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- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 claims description 3
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 claims description 3
- 229920000223 polyglycerol Polymers 0.000 claims description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 3
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- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 3
- 239000005720 sucrose Substances 0.000 claims description 3
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 7
- 238000000034 method Methods 0.000 claims 2
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims 1
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- 238000002649 immunization Methods 0.000 abstract description 9
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- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
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- TWJNQYPJQDRXPH-UHFFFAOYSA-N 2-cyanobenzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1C#N TWJNQYPJQDRXPH-UHFFFAOYSA-N 0.000 description 1
- 241000208340 Araliaceae Species 0.000 description 1
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- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- TUNFSRHWOTWDNC-UHFFFAOYSA-N Myristic acid Natural products CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
- 235000021360 Myristic acid Nutrition 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
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- 230000028996 humoral immune response Effects 0.000 description 1
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Images
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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
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
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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
- A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
- A61K2039/552—Veterinary vaccine
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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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
-
- 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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55577—Saponins; Quil A; QS21; ISCOMS
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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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55583—Polysaccharides
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- General Chemical & Material Sciences (AREA)
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- Animal Behavior & Ethology (AREA)
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- Engineering & Computer Science (AREA)
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The invention discloses a compound water-soluble adjuvant with small stress for producing vaccines, which comprises the following components in parts by weight: 13-75 parts of water for injection, 0.1-10 parts of macromolecular substances, 0.1-10 parts of polymers, 1-19 parts of emulsifying agents, 1-7 parts of auxiliary agents and 0-1 part of immunopotentiators. The composite water-soluble adjuvant with small stress for producing vaccines, which is prepared by the invention, does not contain any forbidden component, and is safe; the compound water-soluble adjuvant is added into the vaccine, can activate and strengthen a plurality of immune channels of the organism, improves the antibody titer of each antigen component of the vaccine after immunization, and simultaneously reduces the side reaction of the organism. Especially for the vaccine of pigs, granuloma generated at the injection position caused by using an oil adjuvant can be avoided, the organism is stimulated to generate higher antibody titer, the duration of the antibody is longer, and the culture benefit is greatly improved. Meanwhile, when the vaccine is prepared into a water phase, the composite water-soluble adjuvant is added into the water phase according to a specific proportion and is uniformly mixed, so that the vaccine can be formed, and the use is convenient.
Description
Technical Field
The invention relates to the technical field of animal vaccines, in particular to a compound water-soluble adjuvant with small stress for producing vaccines and a preparation method thereof.
Background
Adjuvants refer to substances which are applied simultaneously or in advance with an antigen, can enhance the immune response capability of an organism against the antigen, or change the type of immune response; adjuvants play a vital role in vaccines, which can act on both antigens and the body, and proper use of adjuvants can modulate or even alter the type of humoral and/or cellular immune response of the body's immune system that is antigen-specific.
For the body to be exogenous, in addition to the desired immunostimulation, adjuvants are also prone to adverse effects, the benefits of adding adjuvants to vaccine formulations to enhance vaccine immunogenicity must be weighed against the risk of adverse effects; local adverse reactions such as inflammation, nodule, abscess, etc., systemic adverse reactions such as allergy, fever, immunosuppression, even teratogenesis, carcinogenesis, mutation, etc.; with the development of the immunological technology research, people realize that selecting a proper adjuvant becomes a key for enhancing the immunological effect, and the single use of an antigen or only the application of a certain adjuvant has limited effects on improving the reaction intensity, the immune maintenance time, the immune tolerance and the like of the antigen, while the vaccine using the composite water-soluble adjuvant can induce stronger immune response than the vaccine using a single adjuvant, so that the preparation of the composite immune adjuvant by combining different types of adjuvants becomes a new trend of adjuvant development.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a compound water-soluble adjuvant with small stress for producing vaccines and a preparation method thereof, so as to solve the problems in the prior art.
The invention solves the technical problems by adopting the following technical scheme:
the invention provides a compound water-soluble adjuvant with small stress for producing vaccines, which comprises the following components in parts by weight:
13-75 parts of water for injection, 0.1-10 parts of macromolecular substances, 0.1-10 parts of polymers, 1-19 parts of emulsifying agents, 1-7 parts of auxiliary agents and 0-1 part of immunopotentiators.
Preferably, the composition comprises the following components in parts by weight:
44 parts of water for injection, 5 parts of macromolecular substances, 5 parts of polymers, 11 parts of emulsifying agents, 4 parts of auxiliary agents and 1 part of immunopotentiators.
Preferably, the polymer is a natural polymer and/or a synthetic polymer.
Preferably, the polymer is one or more of cyclodextrin, mannan, polymethacrylate, polyvinylpyrrolidone, polylactic-co-glycolic acid (PLGA), cross-linked polyacrylate, polyethylene glycol and polyglycerol.
Preferably, the emulsifier is one or more of sorbitol fatty acid ester, sucrose ester, propylene glycol fatty acid ester, ethylene glycol fatty acid ester, decyl glucoside, coco glucoside, lauryl glucoside and other glucoside, glycerin fatty acid ester and polyglycerin fatty acid ester.
Preferably, the auxiliary agent is one or more of propylene glycol, glycerol, stearic acid, palmitic acid, myristic acid, lauryl alcohol, tetradecyl alcohol and stearyl alcohol.
Preferably, the composite immunopotentiator comprises 0.1-5 parts by weight of DEAE dextran, arginine and saponin, wherein the weight ratio of DEAE dextran, arginine and saponin is (1-2): (1-1.5): (1-1.8).
The saponin is total saponin extracted from stem and leaf of Ginseng radix.
The preparation method of the composite immunopotentiator comprises the following steps:
s1, preparing DEAE dextran solution: 10.0g of DEAE-dextran (molecular weight 5X 105) was weighed, 100ml of water for injection was added thereto, and stirred to dissolve the DEAE-dextran completely, and autoclaved to 10% w/v.
S2, preparing a saponin solution: 10g of saponin was dissolved in distilled water and filtered through a 0.22 μm filter to prepare a 10% (w/v) solution.
S3, preparation of arginine solution: l-arginine 10g was added to distilled water, filtered through a 0.22 μm filter, and filtered through a filter with pH adjusted to 7.8,0.22 μm with phosphoric acid to prepare a 10% (w/v) solution.
Preferably, the arginine is L-arginine or an acid salt thereof.
After arginine is added into the immunopotentiator, the immunopotentiator can be combined with an adjuvant to quickly stimulate the generation of neutralizing antibodies, ensure that the poultry can be protected on the 14 th day after immunization, greatly prolong the immunization duration and maintain the high titer neutralizing antibody titer in a long immunization duration.
The application also provides a preparation method of the composite water-soluble adjuvant with small stress for producing vaccines, which comprises the following steps:
adding glucan, macromolecular substances and polymers into an aqueous solution for dissolution, adding arginine to adjust the pH value to enable the final pH value to be 6.7-7.2, and performing high-pressure sterilization for later use;
step two, adding saponin into vitamin C for dissolution, adding an emulsifying agent and an auxiliary agent, heating to 35-45 ℃, filtering and sterilizing for later use;
and thirdly, uniformly mixing the first step and the second step according to the proportion of four thousandths to obtain the composite water-soluble adjuvant, and adding the composite immunopotentiator to obtain the composite water-soluble adjuvant with small stress for producing the vaccine.
Preferably, in the first step, the aqueous solution is sterilized and cooled, and then added into the aqueous solution prepared in the first step, and the aqueous solution is stirred and mixed uniformly at 1500-3000 r/min.
Preferably, the macromolecular substance is guar gum.
Compared with the prior art, the invention has the following beneficial effects:
the compound water-soluble adjuvant with small stress for producing the vaccine, which is prepared by the invention, achieves the synergistic effect through the compounding of the water for injection, the polymer and the compound immunopotentiator, effectively improves the immune efficacy of the animal vaccine and is beneficial to the immune protection of the animal vaccine.
The composite water-soluble adjuvant with small stress for producing vaccines, which is prepared by the invention, does not contain any forbidden component, and is safe; the compound water-soluble adjuvant is added into the vaccine, can activate and strengthen a plurality of immune channels of the organism, improves the antibody titer of each antigen component of the vaccine after immunization, and simultaneously reduces the side reaction of the organism. Especially for the vaccine of pigs, granuloma generated at the injection position caused by using an oil adjuvant can be avoided, the organism is stimulated to generate higher antibody titer, the duration of the antibody is longer, and the culture benefit is greatly improved. Meanwhile, when the vaccine is prepared into a water phase, the composite water-soluble adjuvant is added into the water phase according to a specific proportion and is uniformly mixed, so that the vaccine can be formed, and the use is convenient.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are needed in the description of the embodiments or the prior art will be briefly described, and it is obvious that the drawings in the description below are some embodiments of the present invention, and other drawings can be obtained according to the drawings without inventive effort for a person skilled in the art.
FIG. 1 is a graph of AIV antibody levels for animal experiments;
FIG. 2 is a graph of NDV antibody levels for animal experiments;
FIG. 3 is a graph of PRRSV antibody levels in animal experiments;
fig. 4 is an absorption effect graph of animal experiments.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and fully with reference to the accompanying drawings, in which it is evident that the embodiments described are only some, but not all embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Example 1.
The compound water-soluble adjuvant with small stress for producing vaccines comprises the following components in parts by weight:
13 parts of water for injection, 10 parts of macromolecular substances, 0.1 part of polymer, 19 parts of emulsifying agent, 1 part of auxiliary agent and 1 part of immunopotentiator.
The polymer of this embodiment is a natural polymer and/or a synthetic polymer.
The polymers of this example are cyclodextrin, mannan, polymethacrylate.
The emulsifier is a surfactant, and hydrophilic groups and lipophilic groups are arranged in the molecule; emulsifiers can be classified into two major classes, water-in-oil (W/O, i.e., lipophilic) and oil-in-water (O/W, i.e., hydrophilic) according to their hydrophilic-lipophilic balance (HLB), the former dispersing water into oil, and the latter dispersing oil into water.
The emulsifier in this example is sorbitol fatty acid ester, sucrose ester, propylene glycol fatty acid ester.
The auxiliary agents in this example were propylene glycol, glycerol, stearic acid, palmitic acid.
The embodiment also comprises 0.1 part of composite immunopotentiator, wherein the composite immunopotentiator comprises DEAE dextran, arginine and saponin, and the weight ratio of the DEAE dextran to the arginine to the saponin is 1:1:1.
the arginine of this example is L-arginine or an acid salt thereof.
The preparation method of the compound water-soluble adjuvant with small stress for producing vaccines comprises the following steps:
adding glucan, macromolecular substances and polymers into an aqueous solution for dissolution, adding arginine to adjust the pH value to enable the final pH value to be 6.7, and performing high-pressure sterilization for later use;
step two, adding saponin into vitamin C for dissolution, adding an emulsifying agent and an auxiliary agent, heating to 35 ℃, filtering and sterilizing for later use;
and thirdly, uniformly mixing the first step and the second step according to the proportion of four thousandths to obtain the composite water-soluble adjuvant, and adding the composite immunopotentiator to obtain the composite water-soluble adjuvant with small stress for producing the vaccine.
In the first step of this embodiment, the aqueous solution is sterilized and cooled, and then added into the aqueous solution prepared in the first step, and stirred and mixed uniformly at 1500 r/min.
Example 2.
The compound water-soluble adjuvant with small stress for producing vaccines comprises the following components in parts by weight:
44 parts of water for injection, 5 parts of macromolecular substances, 5 parts of polymers, 11 parts of emulsifying agents, 4 parts of auxiliary agents and 1 part of immunopotentiators.
The polymer of this embodiment is a natural polymer and/or a synthetic polymer.
The polymers of this example were polyvinylpyrrolidone, polylactic-co-glycolic acid (PLGA), and cross-linked polyacrylate.
The emulsifier is a surfactant, and hydrophilic groups and lipophilic groups are arranged in the molecule; emulsifiers can be classified into two major classes, water-in-oil (W/O, i.e., lipophilic) and oil-in-water (O/W, i.e., hydrophilic) according to their hydrophilic-lipophilic balance (HLB), the former dispersing water into oil, and the latter dispersing oil into water.
The emulsifier of this example is decyl glucoside, coco glucoside, lauryl glucoside or other glucoside, glycerin fatty acid ester, or polyglycerin fatty acid ester.
The adjuvants of this example are myristic acid, lauryl alcohol, tetradecyl alcohol and stearyl alcohol.
The embodiment also comprises 5 parts of composite immunopotentiator, wherein the composite immunopotentiator comprises DEAE dextran, arginine and saponin, and the weight ratio of the DEAE dextran to the arginine to the saponin is 2:1.5:1.8.
the arginine of this example is L-arginine or an acid salt thereof.
The preparation method of the compound water-soluble adjuvant with small stress for producing vaccines comprises the following steps:
adding glucan, macromolecular substances and polymers into an aqueous solution for dissolution, adding arginine to adjust the pH value to enable the final pH value to be 7, and performing high-pressure sterilization for later use;
step two, adding saponin into vitamin C for dissolution, adding an emulsifying agent and an auxiliary agent, heating to 45 ℃, filtering and sterilizing for later use;
and thirdly, uniformly mixing the first step and the second step according to the proportion of four thousandths to obtain the composite water-soluble adjuvant, and adding the composite immunopotentiator to obtain the composite water-soluble adjuvant with small stress for producing the vaccine.
In the first step of this embodiment, the aqueous solution is sterilized and cooled, and then added into the aqueous solution prepared in the first step, and stirred and mixed uniformly at 3000 r/min.
Example 3.
The compound water-soluble adjuvant with small stress for producing vaccines comprises the following components in parts by weight:
75 parts of water for injection, 0.1 part of macromolecular substance, 10 parts of polymer, 1 part of emulsifier, 7 parts of auxiliary agent and 0 part of immunopotentiator.
The polymer of this embodiment is a natural polymer and/or a synthetic polymer.
The polymers of this example are cyclodextrin, polymethacrylate, polylactic-glycolic acid (PLGA), cross-linked polyacrylate and polyglycerol.
The emulsifier is a surfactant, and hydrophilic groups and lipophilic groups are arranged in the molecule; emulsifiers can be classified into two major classes, water-in-oil (W/O, i.e., lipophilic) and oil-in-water (O/W, i.e., hydrophilic) according to their hydrophilic-lipophilic balance (HLB), the former dispersing water into oil, and the latter dispersing oil into water.
The emulsifier of this example is sorbitol fatty acid ester, propylene glycol fatty acid ester, decyl glucoside, coco glucoside, glycerin fatty acid ester.
The adjuvants of this example were propylene glycol, stearic acid, myristic acid and tetradecanol.
The compound immunopotentiator comprises 2.5 parts by weight of DEAE dextran, arginine and saponin, wherein the weight ratio of the DEAE dextran to the arginine to the saponin is 1.5:1.3:1.4.
the arginine of this example is L-arginine or an acid salt thereof.
The preparation method of the compound water-soluble adjuvant with small stress for producing vaccines comprises the following steps:
adding glucan, macromolecular substances and polymers into an aqueous solution for dissolution, adding arginine to adjust the pH value to be 7.2, and performing high-pressure sterilization for later use;
step two, adding saponin into vitamin C for dissolution, adding an emulsifying agent and an auxiliary agent, heating to 40 ℃, filtering and sterilizing for later use;
and thirdly, uniformly mixing the first step and the second step according to the proportion of four thousandths to obtain the composite water-soluble adjuvant, and adding the composite immunopotentiator to obtain the composite water-soluble adjuvant with small stress for producing the vaccine.
In the first step of this embodiment, the aqueous solution is sterilized and cooled, and then added into the aqueous solution prepared in the first step, and uniformly mixed by stirring at 2250 r/min.
The invention is mainly applied to the preparation of inactivated vaccines, and can replace oil emulsion or aluminum gel adjuvant; when preparing the live vaccine, the product is added into the live vaccine according to 5% -25% of the final volume of the vaccine, and the live vaccine can be used after being uniformly mixed, so that the immune effect of the live vaccine can be enhanced. As an application of the invention, the compound water-soluble adjuvant prepared by the invention can be taken orally, and the vaccine for intestinal diseases has good effect when being made into oral vaccine.
As can be seen from fig. 1 and 2, in the composite water-soluble adjuvant vaccine prepared by using the present invention, the AIV antibody levels were not much different before 14 days of immunization compared with the conventional vaccine, but the NDV antibody level of the composite water-soluble adjuvant vaccine prepared by using the present invention was significantly higher than the conventional vaccine, and from 14 days of immunization, the AIV antibody level and the NDV antibody level of the composite water-soluble adjuvant vaccine prepared by the present invention were significantly higher than the conventional vaccine.
As can be seen from fig. 3, in the composite water-soluble adjuvant vaccine prepared by the present invention, compared with the conventional vaccine and ISA201 vaccine (oil adjuvant vaccine), the PRRSV antibody level of the composite water-soluble adjuvant vaccine prepared by the present invention is highest, the PRRSV antibody level of the ISA201 vaccine is inferior, the PRRSV antibody level of the unvaccinated vaccine is the lowest, and the immunization effect and the absorption effect of the water-adjuvant vaccine prepared by the present invention are better than those of the oil adjuvant vaccine after 7 days of immunization.
It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.
Furthermore, it should be understood that although the present disclosure describes embodiments, not every embodiment is provided with a separate embodiment, and that this description is provided for clarity only, and that the disclosure is not limited to the embodiments described in detail below, and that the embodiments described in the examples may be combined as appropriate to form other embodiments that will be apparent to those skilled in the art.
Claims (10)
1. A compound water-soluble adjuvant with small stress for producing vaccine, which is characterized by comprising the following components in parts by weight:
13-75 parts of water for injection, 0.1-10 parts of macromolecular substances, 0.1-10 parts of polymers, 1-19 parts of emulsifying agents, 1-7 parts of auxiliary agents and 0-1 part of immunopotentiators.
2. A complex, water-soluble adjuvant with little stress for the production of vaccines according to claim 1, characterized in that it comprises the following components in parts by weight:
44 parts of water for injection, 5 parts of macromolecular substances, 5 parts of polymers, 11 parts of emulsifying agents, 4 parts of auxiliary agents and 1 part of immunopotentiators.
3. A complex, less stressful, water-soluble adjuvant for use in the manufacture of vaccines according to claim 1 wherein said polymer is a natural polymer and/or a synthetic polymer.
4. A complex, less stressful, water-soluble adjuvant for use in the manufacture of vaccines according to claim 3 wherein the polymer is one or more of cyclodextrin, mannan, polymethacrylate, polyvinylpyrrolidone, polylactic-glycolic acid (PLGA), cross-linked acrylate, polyethylene glycol and polyglycerol.
5. The compound water-soluble adjuvant of claim 1, wherein the emulsifier is one or more of a sorbitol fatty acid ester, sucrose ester, propylene glycol fatty acid ester, ethylene glycol fatty acid ester, decyl glucoside, coco glucoside, lauryl glucoside and the like, a glycerin fatty acid ester and a polyglycerin fatty acid ester.
6. A complex, less stressful, water-soluble adjuvant for use in the manufacture of vaccines according to claim 1 wherein the adjuvant is one or more of propylene glycol, glycerol, stearic acid, palmitic acid, myristic acid, lauryl alcohol, tetradecyl alcohol and stearyl alcohol.
7. The complex water-soluble adjuvant with little stress for producing vaccines according to claim 1, further comprising 0.1 to 5 parts by weight of a complex immunopotentiator comprising DEAE dextran, arginine and saponin in a weight ratio of (1 to 2): (1-1.5): (1-1.8).
8. A complex, less stressful water soluble adjuvant for use in the manufacture of a vaccine according to claim 7 wherein said arginine is L-arginine or an acid salt thereof.
9. The method of preparing a less stressful composite water soluble adjuvant for use in the production of vaccines according to any of claims 1 to 8 comprising the steps of:
adding glucan, macromolecular substances and polymers into an aqueous solution for dissolution, adding arginine to adjust the pH value to enable the final pH value to be 6.7-7.2, and performing high-pressure sterilization for later use;
step two, adding saponin into vitamin C for dissolution, adding an emulsifying agent and an auxiliary agent, heating to 35-45 ℃, filtering and sterilizing for later use;
and thirdly, uniformly mixing the first step and the second step according to the proportion of four thousandths to obtain the composite water-soluble adjuvant, and adding the composite immunopotentiator to obtain the composite water-soluble adjuvant with small stress for producing the vaccine.
10. The method for preparing a compound water-soluble adjuvant with small stress for vaccine production according to claim 9, wherein in the first step, the aqueous solution is sterilized and cooled, and then added into the aqueous solution prepared in the first step, and the mixture is stirred and mixed uniformly at 1500-3000 r/min.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105816873A (en) * | 2016-03-11 | 2016-08-03 | 中牧实业股份有限公司 | Polymer combined adjuvant of animal vaccine and applications thereof |
| CN113893340A (en) * | 2021-09-30 | 2022-01-07 | 中牧实业股份有限公司 | Stabilizer of foot-and-mouth disease vaccine with biphasic oil adjuvant and application thereof |
| CN113967252A (en) * | 2020-07-24 | 2022-01-25 | 洛阳赛威生物科技有限公司 | Immunopotentiator for poultry, vaccine composition containing immunopotentiator and application of vaccine composition |
| US20220047699A1 (en) * | 2018-12-24 | 2022-02-17 | LUOYANG SEIWEI BIOTECHNOLOGIES Co.,Ltd. | Immunological adjuvant composition, preparation method and application thereof |
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- 2023-05-18 CN CN202310564030.4A patent/CN116370620A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105816873A (en) * | 2016-03-11 | 2016-08-03 | 中牧实业股份有限公司 | Polymer combined adjuvant of animal vaccine and applications thereof |
| US20220047699A1 (en) * | 2018-12-24 | 2022-02-17 | LUOYANG SEIWEI BIOTECHNOLOGIES Co.,Ltd. | Immunological adjuvant composition, preparation method and application thereof |
| CN113967252A (en) * | 2020-07-24 | 2022-01-25 | 洛阳赛威生物科技有限公司 | Immunopotentiator for poultry, vaccine composition containing immunopotentiator and application of vaccine composition |
| CN113893340A (en) * | 2021-09-30 | 2022-01-07 | 中牧实业股份有限公司 | Stabilizer of foot-and-mouth disease vaccine with biphasic oil adjuvant and application thereof |
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