CN118021949A - Traditional Chinese medicine adjuvant for hepatitis A vaccine and preparation method thereof - Google Patents
Traditional Chinese medicine adjuvant for hepatitis A vaccine and preparation method thereof Download PDFInfo
- Publication number
- CN118021949A CN118021949A CN202311112169.1A CN202311112169A CN118021949A CN 118021949 A CN118021949 A CN 118021949A CN 202311112169 A CN202311112169 A CN 202311112169A CN 118021949 A CN118021949 A CN 118021949A
- Authority
- CN
- China
- Prior art keywords
- parts
- mixed solution
- traditional chinese
- chinese medicine
- flavone
- 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.)
- Pending
Links
- 239000002671 adjuvant Substances 0.000 title claims abstract description 49
- 239000003814 drug Substances 0.000 title claims abstract description 49
- 229940124724 hepatitis-A vaccine Drugs 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 150000004676 glycans Chemical class 0.000 claims abstract description 36
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 36
- 239000005017 polysaccharide Substances 0.000 claims abstract description 36
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims abstract description 32
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 claims abstract description 31
- 229930003944 flavone Natural products 0.000 claims abstract description 31
- 150000002212 flavone derivatives Chemical class 0.000 claims abstract description 31
- 235000011949 flavones Nutrition 0.000 claims abstract description 31
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 claims abstract description 31
- 239000001397 quillaja saponaria molina bark Substances 0.000 claims abstract description 19
- 229930182490 saponin Natural products 0.000 claims abstract description 19
- 150000007949 saponins Chemical class 0.000 claims abstract description 19
- PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 claims abstract description 16
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 claims abstract description 16
- 239000004322 Butylated hydroxytoluene Substances 0.000 claims abstract description 16
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 claims abstract description 16
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229940095259 butylated hydroxytoluene Drugs 0.000 claims abstract description 16
- 235000010354 butylated hydroxytoluene Nutrition 0.000 claims abstract description 16
- 235000012000 cholesterol Nutrition 0.000 claims abstract description 16
- 125000001446 muramyl group Chemical group N[C@@H](C=O)[C@@H](O[C@@H](C(=O)*)C)[C@H](O)[C@H](O)CO 0.000 claims abstract description 16
- 229940083466 soybean lecithin Drugs 0.000 claims abstract description 16
- 239000002994 raw material Substances 0.000 claims abstract description 10
- 239000011259 mixed solution Substances 0.000 claims description 61
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 30
- 239000002502 liposome Substances 0.000 claims description 24
- 238000002156 mixing Methods 0.000 claims description 18
- 239000007788 liquid Substances 0.000 claims description 14
- 238000003756 stirring Methods 0.000 claims description 8
- 239000007853 buffer solution Substances 0.000 claims description 6
- 238000004108 freeze drying Methods 0.000 claims description 6
- 238000007710 freezing Methods 0.000 claims description 6
- 230000008014 freezing Effects 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 239000000725 suspension Substances 0.000 claims description 6
- 238000010257 thawing Methods 0.000 claims description 6
- 239000002691 unilamellar liposome Substances 0.000 claims description 6
- 241001061264 Astragalus Species 0.000 claims description 5
- 244000068988 Glycine max Species 0.000 claims description 5
- 235000010469 Glycine max Nutrition 0.000 claims description 5
- 240000000950 Hippophae rhamnoides Species 0.000 claims description 5
- 235000003145 Hippophae rhamnoides Nutrition 0.000 claims description 5
- 229930189092 Notoginsenoside Natural products 0.000 claims description 5
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 claims description 5
- 235000003140 Panax quinquefolius Nutrition 0.000 claims description 5
- 235000006533 astragalus Nutrition 0.000 claims description 5
- 235000008434 ginseng Nutrition 0.000 claims description 5
- 229930182494 ginsenoside Natural products 0.000 claims description 5
- 229940089161 ginsenoside Drugs 0.000 claims description 5
- 210000004233 talus Anatomy 0.000 claims description 5
- 241001165494 Rhodiola Species 0.000 claims description 4
- 244000175448 Citrus madurensis Species 0.000 claims description 3
- 241000218158 Clematis Species 0.000 claims description 3
- 235000017317 Fortunella Nutrition 0.000 claims description 3
- 241000594394 Hedyotis Species 0.000 claims description 3
- 241000222640 Polyporus Species 0.000 claims description 3
- 244000126002 Ziziphus vulgaris Species 0.000 claims description 3
- 229930187479 gypenoside Natural products 0.000 claims description 2
- ZRBFCAALKKNCJG-UHFFFAOYSA-N gypenoside-XVII Natural products C1CC(C2(CCC3C(C)(C)C(OC4C(C(O)C(O)C(CO)O4)O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC(C(C(O)C1O)O)OC1COC1OC(CO)C(O)C(O)C1O ZRBFCAALKKNCJG-UHFFFAOYSA-N 0.000 claims description 2
- 238000000034 method Methods 0.000 claims 2
- 244000131316 Panax pseudoginseng Species 0.000 claims 1
- 229960005486 vaccine Drugs 0.000 abstract description 6
- 230000036039 immunity Effects 0.000 abstract description 4
- 230000002708 enhancing effect Effects 0.000 abstract description 3
- 230000000813 microbial effect Effects 0.000 abstract description 3
- 230000000295 complement effect Effects 0.000 abstract description 2
- 239000000427 antigen Substances 0.000 description 6
- 102000036639 antigens Human genes 0.000 description 6
- 108091007433 antigens Proteins 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 5
- 241000208340 Araliaceae Species 0.000 description 4
- 229910052782 aluminium Inorganic materials 0.000 description 4
- 239000000568 immunological adjuvant Substances 0.000 description 4
- 230000028993 immune response Effects 0.000 description 3
- 230000001571 immunoadjuvant effect Effects 0.000 description 3
- 229930186669 gynosaponin Natural products 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 229940126680 traditional chinese medicines Drugs 0.000 description 2
- 206010007269 Carcinogenicity Diseases 0.000 description 1
- 240000006509 Gynostemma pentaphyllum Species 0.000 description 1
- 235000002956 Gynostemma pentaphyllum Nutrition 0.000 description 1
- 241000709721 Hepatovirus A Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 244000042430 Rhodiola rosea Species 0.000 description 1
- 235000003713 Rhodiola rosea Nutrition 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 231100000260 carcinogenicity Toxicity 0.000 description 1
- 230000007670 carcinogenicity Effects 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000007365 immunoregulation Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000012646 vaccine adjuvant Substances 0.000 description 1
- 229940124931 vaccine adjuvant Drugs 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- 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
-
- 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
- A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
-
- 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Virology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Medicinal Preparation (AREA)
Abstract
The application discloses a traditional Chinese medicine adjuvant for a hepatitis A vaccine and a preparation method thereof, belonging to the technical field of vaccine preparation. The traditional Chinese medicine adjuvant comprises the following raw materials in parts by weight: 20-30 parts of soybean lecithin, 5-10 parts of cholesterol, 1-2 parts of butylated hydroxytoluene, 0.5-2 parts of stearylamine, 0.5-3 parts of phosphatidic acid, 1-5 parts of saponin, 2-3 parts of muramyl tripeptide, 2-4 parts of polysaccharide and 2-5 parts of flavone. The application combines traditional Chinese medicine components and microbial immunity to realize complementary advantages, and can play a good role in enhancing immunity by adding saponin, polysaccharide and flavone to form a traditional Chinese medicine adjuvant which is applied to the preparation process of hepatitis A vaccine.
Description
Technical Field
The invention relates to the technical field of vaccine preparation, in particular to a traditional Chinese medicine adjuvant for hepatitis A vaccine and a preparation method thereof.
Background
The immunoadjuvant is a substance capable of nonspecifically changing or enhancing specific immune response of an organism to an antigen, and is required to be free from carcinogenicity, free from toxicity, high in purity, degradable, capable of having a certain adsorption capacity and stable in property. The principle of action of the immunoadjuvant is mainly represented by the following three aspects: first, increasing the surface area of the antigen, and improving the immunogenicity thereof; secondly, the slow release effect is exerted on the antigen, and the residence time of the antigen in the tissue is prolonged; third, promote inflammatory responses, stimulating active immune responses. That is, the immune adjuvant is mainly used for pre-stimulating the immune system through false images, so that the immune adjuvant is considered as an antigen, and can cause the immune response of an organism earlier. The immunological adjuvants commonly used at present are aluminum adjuvants, freund's adjuvants, cpG DNA adjuvants, nanoadjuvants, microbial and metabolite adjuvants and the like. The Freund's adjuvant has much higher activity than other adjuvants, but has too strong side effects to be popularized and used. Aluminum adjuvants are currently the only immunoadjuvant approved for use in human vaccines, and are used in a variety of liquid vaccines. However, the aluminum adjuvant can only induce humoral immunity and cannot induce cellular immunity, which increases the application limitation, and the combination ability of the aluminum adjuvant and antigen is not stable enough, and the potential toxic and side effects of liquid aluminum element in the vaccine after large-dose injection are also emphasized. Therefore, the search for a novel immune adjuvant with high efficiency and safety has become an important subject in the field of contemporary immunology research.
The traditional Chinese medicine is an important component of the traditional medical theory in China, and has a unique theoretical system and application form. Modern researches show that the active ingredients of some traditional Chinese medicines have good immunoregulation effect, and the traditional Chinese medicines have high biological affinity as natural products, mild and durable effects, have remarkable advantages as novel vaccine adjuvants, and are paid more attention to.
Disclosure of Invention
The invention aims to provide a traditional Chinese medicine adjuvant for a hepatitis A vaccine, which can enhance the immune effect of the vaccine.
In order to achieve the purpose, the invention firstly provides a traditional Chinese medicine adjuvant for hepatitis A vaccine, which has the following specific technical scheme:
a traditional Chinese medicine adjuvant for hepatitis A vaccine comprises the following raw materials in parts by weight: 20-30 parts of soybean lecithin, 5-10 parts of cholesterol, 1-2 parts of butylated hydroxytoluene, 0.5-2 parts of stearylamine, 0.5-3 parts of phosphatidic acid, 1-5 parts of saponin, 2-3 parts of muramyl tripeptide, 2-4 parts of polysaccharide and 2-5 parts of flavone.
Preferably, the traditional Chinese medicine adjuvant comprises the following raw materials in parts by weight: 25 parts of soybean lecithin, 5 parts of cholesterol, 1 part of butylated hydroxytoluene, 1 part of stearylamine, 0.5 part of phosphatidic acid, 5 parts of saponin, 3 parts of muramyl tripeptide, 2 parts of polysaccharide and 4 parts of flavone.
Preferably, the saponin is one or more of ginsenoside, notoginsenoside, gynosaponin and clematis root saponin.
Preferably, the polysaccharide is one or more of astragalus polysaccharide, ginseng polysaccharide, polyporus polysaccharide, rhodiola polysaccharide and jujube polysaccharide.
Preferably, the flavone is one or more of kumquat flavone, hedyotis flavone, soybean flavone and seabuckthorn flavone.
In addition, the invention also provides a preparation method of the traditional Chinese medicine adjuvant for the hepatitis A vaccine, which comprises the following steps:
(1) Uniformly mixing soybean lecithin and cholesterol according to the weight parts to obtain a mixed solution 1, uniformly mixing butylated hydroxytoluene, stearylamine and phosphatidic acid to obtain a mixed solution 2, and pouring the mixed solution 2 into the mixed solution 1 to obtain a mixed solution 3;
(2) Dissolving the obtained mixed solution 3 in an organic solvent to obtain a mixed solution 4, injecting the mixed solution 4 into a buffer solution heated to 50-58 ℃ to obtain a mixed solution 5, and stirring the mixed solution 5 until the organic solvent is completely volatilized to obtain a large porous liposome;
(3) The obtained suspension of the porous liposome is processed by a high-pressure homogenizer to obtain large single-chamber liposome;
(4) Mixing the obtained large unilamellar liposome with saponin, muramyl tripeptide, polysaccharide and flavone according to the parts by weight to obtain a liquid medicine 1;
(5) And (3) continuously freezing and thawing the obtained liquid medicine 1 to form uniform small single-chamber liposome, and freeze-drying to obtain the traditional Chinese medicine adjuvant finished product.
Preferably, the organic solvent in step (2) is diethyl ether.
Preferably, the stirring of the mixed liquor 5 in the step (2) is carried out for 1-2h.
The beneficial effects of the invention are that
Compared with the prior art, the traditional Chinese medicine adjuvant for the hepatitis A vaccine and the preparation method thereof realize complementary advantages by combining traditional Chinese medicine components with microbial immunity, and can play a good role in enhancing immunity by adding saponin, polysaccharide and flavone to form the traditional Chinese medicine adjuvant in the preparation process of the hepatitis A vaccine.
Detailed Description
A traditional Chinese medicine adjuvant for hepatitis A vaccine comprises the following raw materials in parts by weight: 20-30 parts of soybean lecithin, 5-10 parts of cholesterol, 1-2 parts of butylated hydroxytoluene, 0.5-2 parts of stearylamine, 0.5-3 parts of phosphatidic acid, 1-5 parts of saponin, 2-3 parts of muramyl tripeptide, 2-4 parts of polysaccharide and 2-5 parts of flavone. Preferably, the saponin is one or more of ginsenoside, notoginsenoside, gynosaponin and clematis root saponin. Preferably, the polysaccharide is one or more of astragalus polysaccharide, ginseng polysaccharide, polyporus polysaccharide, rhodiola polysaccharide and jujube polysaccharide. Preferably, the flavone is one or more of kumquat flavone, hedyotis flavone, soybean flavone and seabuckthorn flavone.
Preferably, the traditional Chinese medicine adjuvant comprises the following raw materials in parts by weight: 25 parts of soybean lecithin, 5 parts of cholesterol, 1 part of butylated hydroxytoluene, 1 part of stearylamine, 0.5 part of phosphatidic acid, 5 parts of saponin, 3 parts of muramyl tripeptide, 2 parts of polysaccharide and 4 parts of flavone.
In addition, the invention also provides a preparation method of the traditional Chinese medicine adjuvant for the hepatitis A vaccine, which comprises the following steps:
(1) Uniformly mixing soybean lecithin and cholesterol according to the weight parts to obtain a mixed solution 1, uniformly mixing butylated hydroxytoluene, stearylamine and phosphatidic acid to obtain a mixed solution 2, and pouring the mixed solution 2 into the mixed solution 1 to obtain a mixed solution 3;
(2) Dissolving the obtained mixed solution 3 in diethyl ether to obtain mixed solution 4, injecting the mixed solution 4 into a buffer solution heated to 50-58 ℃ to obtain mixed solution 5, and stirring the mixed solution 5 for 1-2h until the diethyl ether is completely volatilized to obtain a large porous liposome;
(3) The obtained suspension of the porous liposome is processed by a high-pressure homogenizer to obtain large single-chamber liposome;
(4) Mixing the obtained large unilamellar liposome with saponin, muramyl tripeptide, polysaccharide and flavone according to the parts by weight to obtain a liquid medicine 1;
(5) And (3) continuously freezing and thawing the obtained liquid medicine 1 to form uniform small single-chamber liposome, and freeze-drying to obtain the traditional Chinese medicine adjuvant finished product.
Example 1
A traditional Chinese medicine adjuvant for hepatitis A vaccine comprises the following raw materials in parts by weight: 25 parts of soybean lecithin, 5 parts of cholesterol, 1 part of butylated hydroxytoluene, 1 part of stearylamine, 0.5 part of phosphatidic acid, 5 parts of ginsenoside, 3 parts of muramyl tripeptide, 2 parts of ginseng polysaccharide and 4 parts of Jin Juhuang ketone.
In addition, the invention also provides a preparation method of the traditional Chinese medicine adjuvant for the hepatitis A vaccine, which comprises the following steps:
(1) Uniformly mixing soybean lecithin and cholesterol according to the weight parts to obtain a mixed solution 1, uniformly mixing butylated hydroxytoluene, stearylamine and phosphatidic acid to obtain a mixed solution 2, and pouring the mixed solution 2 into the mixed solution 1 to obtain a mixed solution 3;
(2) Dissolving the obtained mixed solution 3 in diethyl ether to obtain mixed solution 4, injecting the mixed solution 4 into buffer solution heated to 58 ℃ to obtain mixed solution 5, and stirring the mixed solution 5 for 2 hours until the diethyl ether is completely volatilized to obtain a large porous liposome;
(3) The obtained suspension of the porous liposome is processed by a high-pressure homogenizer to obtain large single-chamber liposome;
(4) Mixing the obtained large unilamellar liposome with ginsenoside, muramyl tripeptide, ginseng polysaccharide and Jin Juhuang ketone according to the weight portion to obtain a liquid medicine 1;
(5) And (3) continuously freezing and thawing the obtained liquid medicine 1 to form uniform small single-chamber liposome, and freeze-drying to obtain the traditional Chinese medicine adjuvant finished product.
Example 2
A traditional Chinese medicine adjuvant for hepatitis A vaccine comprises the following raw materials in parts by weight: 30 parts of soybean lecithin, 10 parts of cholesterol, 2 parts of butylated hydroxytoluene, 0.5 part of stearylamine, 3 parts of phosphatidic acid, 3 parts of notoginsenoside, 3 parts of muramyl tripeptide, 2 parts of astragalus polysaccharide and 3 parts of soybean flavone.
In addition, the invention also provides a preparation method of the traditional Chinese medicine adjuvant for the hepatitis A vaccine, which comprises the following steps:
(1) Uniformly mixing soybean lecithin and cholesterol according to the weight parts to obtain a mixed solution 1, uniformly mixing butylated hydroxytoluene, stearylamine and phosphatidic acid to obtain a mixed solution 2, and pouring the mixed solution 2 into the mixed solution 1 to obtain a mixed solution 3;
(2) Dissolving the obtained mixed solution 3 in diethyl ether to obtain mixed solution 4, injecting the mixed solution 4 into buffer solution heated to 50 ℃ to obtain mixed solution 5, and stirring the mixed solution 5 for 1h until the diethyl ether is completely volatilized to obtain a large porous liposome;
(3) The obtained suspension of the porous liposome is processed by a high-pressure homogenizer to obtain large single-chamber liposome;
(4) Mixing the obtained large unilamellar liposome with notoginsenoside, muramyl tripeptide, astragalus polysaccharide and soybean flavone according to the parts by weight to obtain a liquid medicine 1;
(5) And (3) continuously freezing and thawing the obtained liquid medicine 1 to form uniform small single-chamber liposome, and freeze-drying to obtain the traditional Chinese medicine adjuvant finished product.
Example 3
A traditional Chinese medicine adjuvant for hepatitis A vaccine comprises the following raw materials in parts by weight: 20 parts of soybean lecithin, 8 parts of cholesterol, 1 part of butylated hydroxytoluene, 1 part of stearylamine, 2 parts of phosphatidic acid, 2 parts of gynostemma pentaphylla saponin, 3 parts of muramyl tripeptide, 4 parts of rhodiola rosea polysaccharide and 5 parts of seabuckthorn flavone.
In addition, the invention also provides a preparation method of the traditional Chinese medicine adjuvant for the hepatitis A vaccine, which comprises the following steps:
(1) Uniformly mixing soybean lecithin and cholesterol according to the weight parts to obtain a mixed solution 1, uniformly mixing butylated hydroxytoluene, stearylamine and phosphatidic acid to obtain a mixed solution 2, and pouring the mixed solution 2 into the mixed solution 1 to obtain a mixed solution 3;
(2) Dissolving the obtained mixed solution 3 in diethyl ether to obtain mixed solution 4, injecting the mixed solution 4 into buffer solution heated to 55 ℃ to obtain mixed solution 5, and stirring the mixed solution 5 for 1.5 hours until the diethyl ether is completely volatilized to obtain large porous liposome;
(3) The obtained suspension of the porous liposome is processed by a high-pressure homogenizer to obtain large single-chamber liposome;
(4) Mixing the obtained large unilamellar liposome with gypenoside, muramyl tripeptide, rhodiola polysaccharide and seabuckthorn flavone according to the weight parts to obtain a liquid medicine 1;
(5) And (3) continuously freezing and thawing the obtained liquid medicine 1 to form uniform small single-chamber liposome, and freeze-drying to obtain the traditional Chinese medicine adjuvant finished product.
The traditional Chinese medicine adjuvant finished product obtained by the preparation method in the example 3 is applied to hepatitis A vaccine and a control group is arranged, and the result shows that the antibody level of the hepatitis A virus of the mice in the experimental group is higher than that of the control group.
Claims (8)
1. The traditional Chinese medicine adjuvant for the hepatitis A vaccine is characterized by comprising the following raw materials in parts by weight: 20-30 parts of soybean lecithin, 5-10 parts of cholesterol, 1-2 parts of butylated hydroxytoluene, 0.5-2 parts of stearylamine, 0.5-3 parts of phosphatidic acid, 1-5 parts of saponin, 2-3 parts of muramyl tripeptide, 2-4 parts of polysaccharide and 2-5 parts of flavone.
2. The traditional Chinese medicine adjuvant for hepatitis A vaccine according to claim 1, which is characterized by comprising the following raw materials in parts by weight: 25 parts of soybean lecithin, 5 parts of cholesterol, 1 part of butylated hydroxytoluene, 1 part of stearylamine, 0.5 part of phosphatidic acid, 5 parts of saponin, 3 parts of muramyl tripeptide, 2 parts of polysaccharide and 4 parts of flavone.
3. The adjuvant according to claim 1, wherein the saponin is one or more of ginsenoside, notoginsenoside, gypenoside and clematis root saponin.
4. The adjuvant according to claim 1, wherein the polysaccharide is one or more of astragalus polysaccharides, ginseng polysaccharides, polyporus polysaccharides, rhodiola polysaccharides and jujube polysaccharides.
5. The adjuvant according to claim 1, wherein the flavone is any one or more of kumquat flavone, hedyotis flavone, soybean flavone and seabuckthorn flavone.
6. The preparation method of the traditional Chinese medicine adjuvant for the hepatitis A vaccine is characterized by comprising the following steps of:
(1) Uniformly mixing soybean lecithin and cholesterol according to the weight parts to obtain a mixed solution 1, uniformly mixing butylated hydroxytoluene, stearylamine and phosphatidic acid to obtain a mixed solution 2, and pouring the mixed solution 2 into the mixed solution 1 to obtain a mixed solution 3;
(2) Dissolving the obtained mixed solution 3 in an organic solvent to obtain a mixed solution 4, injecting the mixed solution 4 into a buffer solution heated to 50-58 ℃ to obtain a mixed solution 5, and stirring the mixed solution 5 until the organic solvent is completely volatilized to obtain a large porous liposome;
(3) The obtained suspension of the porous liposome is processed by a high-pressure homogenizer to obtain large single-chamber liposome;
(4) Mixing the obtained large unilamellar liposome with saponin, muramyl tripeptide, polysaccharide and flavone according to the parts by weight to obtain a liquid medicine 1;
(5) And (3) continuously freezing and thawing the obtained liquid medicine 1 to form uniform small single-chamber liposome, and freeze-drying to obtain the traditional Chinese medicine adjuvant finished product.
7. The method for preparing a traditional Chinese medicine adjuvant for hepatitis A vaccine according to claim 6, wherein the organic solvent in the step (2) is diethyl ether.
8. The method for preparing a traditional Chinese medicine adjuvant for hepatitis A vaccine according to claim 6, wherein the stirring of the mixed solution 5 in the step (2) is carried out for 1-2 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311112169.1A CN118021949A (en) | 2023-08-31 | 2023-08-31 | Traditional Chinese medicine adjuvant for hepatitis A vaccine and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311112169.1A CN118021949A (en) | 2023-08-31 | 2023-08-31 | Traditional Chinese medicine adjuvant for hepatitis A vaccine and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN118021949A true CN118021949A (en) | 2024-05-14 |
Family
ID=91001020
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311112169.1A Pending CN118021949A (en) | 2023-08-31 | 2023-08-31 | Traditional Chinese medicine adjuvant for hepatitis A vaccine and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN118021949A (en) |
-
2023
- 2023-08-31 CN CN202311112169.1A patent/CN118021949A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9517262B2 (en) | Vaccine injection, preparation method and use thereof | |
| CN104013955B (en) | A kind of not containing O/w emulsion and uses thereof of surfactant | |
| DE69431358T2 (en) | METHOD AND COMPOSITIONS FOR MICROCAPSULATING ADJUVANTS | |
| CN101402666B (en) | Saponin with immunoadjuvant function, preparation method, vaccine preparation containing the saponin as adjuvant and uses thereof | |
| EP0678035B9 (en) | Vaccine preparations | |
| CN104043120B (en) | Hepatitis b vaccine | |
| Nguyen et al. | Skin immunization with third-generation hepatitis B surface antigen using microneedles | |
| CN118021949A (en) | Traditional Chinese medicine adjuvant for hepatitis A vaccine and preparation method thereof | |
| CN101244267B (en) | Immunity preparation for reinforcing microorganism vaccine immunogenicity | |
| Osorio et al. | Immune responses to hepatitis B surface antigen following epidermal powder immunization | |
| CN100464755C (en) | Traditional Chinese medicine preparation with functions of immunological regulation for anti-chemical damage | |
| CN103768593A (en) | Cortex albiziae saponin adjuvant and preparation method thereof, as well as vaccine preparation containing adjuvant and application thereof | |
| CN103816210A (en) | Pueraria lobata extract and application thereof | |
| CN102764435A (en) | Porcine Asian type-I foot-and-mouth disease virus inactivated vaccine adjuvant and preparation method thereof | |
| CN1249072C (en) | Preparation method of golden peach glycoside and its new use in medicine | |
| CN105169386B (en) | A kind of novel universal type matrix vaccines adjuvant and its preparation method and application | |
| CN103251667B (en) | Application of general inula helenium sesquiterpene lactone in preparation of medicine for treating rheumatoid arthritis | |
| CN112294955A (en) | Compound immunologic adjuvant and application thereof | |
| CN101675994B (en) | Therapy vaccine preparation | |
| Miao et al. | Immuno-Enhancing Effect of Ginsenoside Rh2 Liposomes on Foot-and-Mouth Disease Vaccine | |
| CN101380472B (en) | Use of total saponin from Panax notoginseng stalks and leaves in preparing immunoadjuvants | |
| CN1990043B (en) | Use of recombinant human granulocyte macrophagocyte colony stimulating factor in preparation of drug for preventing and treating hepatitis B | |
| CN109674942A (en) | A kind of Antilipidemic pharmaceutical compositions, preparation method and applications | |
| CN109223739A (en) | A kind of composition and its preparation method and application | |
| CN105288615A (en) | Vaccine adjuvant and adjuvant vaccine prepared through the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |