CN106177942A - A kind of for living paratyphoid vaccine for piglets adjuvant - Google Patents

A kind of for living paratyphoid vaccine for piglets adjuvant Download PDF

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Publication number
CN106177942A
CN106177942A CN201610684088.2A CN201610684088A CN106177942A CN 106177942 A CN106177942 A CN 106177942A CN 201610684088 A CN201610684088 A CN 201610684088A CN 106177942 A CN106177942 A CN 106177942A
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China
Prior art keywords
adjuvant
piglets
aluminium hydroxide
hydroxide gel
vaccine
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Pending
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CN201610684088.2A
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Chinese (zh)
Inventor
李炳更
马景霞
董新荣
张静
孙延云
薛莹
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SHANDONG BINZHOU BOLAIWEI BIOTECH CO Ltd
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SHANDONG BINZHOU BOLAIWEI BIOTECH CO Ltd
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Priority to CN201610684088.2A priority Critical patent/CN106177942A/en
Publication of CN106177942A publication Critical patent/CN106177942A/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/39Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/02Bacterial antigens
    • A61K39/025Enterobacteriales, e.g. Enterobacter
    • A61K39/0275Salmonella
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/51Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/52Bacterial cells; Fungal cells; Protozoal cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/55Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
    • A61K2039/552Veterinary vaccine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/555Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55505Inorganic adjuvants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/555Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511Organic adjuvants
    • A61K2039/55583Polysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/555Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55588Adjuvants of undefined constitution

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

The invention discloses a kind of for living paratyphoid vaccine for piglets adjuvant, aluminium hydroxide gel, calcium phosphate, vitamin E, lentinan, lanoline are organically combined by the present invention, coordinate mutually, prepare the immunity composite adjuvant for living paratyphoid vaccine for piglets, play the sharpest edges of adjuvant, share immune effect preferably with antigen, toxicity is little, low cost.The side effect of vaccine can be significantly reduced, and improve immune effect.

Description

A kind of for living paratyphoid vaccine for piglets adjuvant
Technical field
The present invention relates to vaccine adjuvant technical field, particularly relate to a kind of for living paratyphoid vaccine for piglets adjuvant.
Background technology
Baby swine paratyphoid is also referred to as pig salmonellosis, is by a kind of infectious disease of salmonellal piglet.Acute person is for losing Mass formed by blood stasis, chronic person is necrotic enteritis, often betides 6 monthly ages below piglet, and particularly 2~4 monthly age piglets are common, throughout the year All can occur, when rainy humidity, cold, season alternation, incidence rate is high.After existing baby swine paratyphoid vaccine injection, some pig is anti- Should be relatively big, some piglets there will be body temperature and raise, shake, vomit and subtract the symptoms such as food.
Adjuvant is initially to be described as a kind of material with specific antigen use in conjunction by Gaston Ramon , and with the specific antigen of adjuvant use in conjunction now produced immunne response when being used alone than it much higher.
Adjuvant is nonspecific immunity strengthening agent, when injecting together with antigen or being previously implanted body, and can enhancing body Immunne response or change type of immune response to antigen.It is the physics by changing antigen that adjuvant strengthens the mechanism of immunne response Shape, extends antigen retention time in body;Stimulate the mononuclear phagocyte submission ability to antigen;Lymphocyte is stimulated to divide Change, increase and expand immunne response ability.
Existing immunological adjuvant, because weak effect or virulence are big, especially lacking of property, do not have one to be satisfied with Effect.Therefore it is an object of the invention to provide a kind of immunologic adjuvant for living paratyphoid vaccine for piglets.
Summary of the invention
The purpose of the present invention is aiming at the defect of above-mentioned existence and provides a kind of for living paratyphoid vaccine for piglets adjuvant, The present invention by aluminium hydroxide gel, calcium phosphate, vitamin E, lentinan, lanoline organically combine, coordinate mutually, prepare for The immunity composite adjuvant of living paratyphoid vaccine for piglets, plays the sharpest edges of adjuvant, share immune effect preferably with antigen, toxicity Little, low cost.The side effect of vaccine can be significantly reduced, and improve immune effect.
The one of the present invention for living paratyphoid vaccine for piglets adjuvant technical scheme is, including aluminium hydroxide gel, calcium phosphate, Vitamin E, lentinan, lanoline.
Described one is used for living paratyphoid vaccine for piglets adjuvant, the following component including by weight: aluminium hydroxide gel 20-60, calcium phosphate 20-40, vitamin e1 0-20, lentinan 1-10, lanoline 10-30.
Described one is used for living paratyphoid vaccine for piglets adjuvant, the following component including by weight: aluminium hydroxide gel 30-55, calcium phosphate 25-35, vitamin e1 2-16, lentinan 2-8, lanoline 15-20.
Described one is used for living paratyphoid vaccine for piglets adjuvant, the following component including by weight: aluminium hydroxide gel 38, calcium phosphate 30, vitamin e1 5, lentinan 4, lanoline 17.
The preparation method of aluminium hydroxide gel is: by the soda of the Alumen of mass concentration 25%-28% Yu mass concentration 10-12% Solution, is stirred continuously with 60rpm speed, pH value 6.5-6.8 50 DEG C~60 DEG C mixing in temperature, is passed through steam pipe and carries out ripe Change, drive away CO2Make colloidal state thinning, burnt hair, blue or green bright for ripening standard, blow the boiling time to there is no a large amount of bubble, pH7.6~ Between 7.8;Adding cold water makes ripening glue temperature drop to less than 75 DEG C, stirs;Washing after draining mother solution, washing water temperature exists 50~55 DEG C, smash glue salt with splash bar during washing, stir, wash 5-6 time, after checking that sulfate is qualified, stop washing;Make Glue amount moisture content obtains aluminium hydroxide gel when taking off 2~2.5 times to about Alumen inventory.
Described one is used for living paratyphoid vaccine for piglets adjuvant, and preparation method is:
(1) physiological saline solution aluminium hydroxide gel is used;
(2) adding in aluminium hydroxide gel mixed liquor of normal saline by calcium phosphate, vitamin E, lentinan, lanoline, mixing is all Even, adjust pH to make adjuvant to 6.5.
In step (1), using physiological saline solution aluminium hydroxide gel, aluminium hydroxide gel mass percentage content is 20%.
Antigen is added in adjuvant according to the weight ratio of 1:1, according to 3000rpm, emulsifying 30 minutes.
The invention have the benefit that the present invention is by aluminium hydroxide gel, calcium phosphate, vitamin E, lentinan, lanoline Organically combining, coordinate mutually, prepare the immunity composite adjuvant for living paratyphoid vaccine for piglets, the maximum playing adjuvant is excellent Gesture, share immune effect preferably with antigen, and toxicity is little, low cost.The side effect of vaccine can be significantly reduced, and improve immunity effect Really.
Adjuvant of the present invention is combined with living paratyphoid vaccine for piglets antigen, forms optimal formula, i.e. forms immunostimulation multiple Compound, preferably plays immunological adjuvant effect.Apply this adjuvant and be used alone aluminium hydroxide gel adjuvant or use existing Freund adjuvant, it is respectively configured living paratyphoid vaccine for piglets live vaccine immune animal, applies its antibody titer of adjuvant group of the present invention equal Apparently higher than being used alone adsorbed onto alum adjuvant or using existing Freund adjuvant experimental group, exceed 8-12 antibody titer.
Detailed description of the invention:
In order to be more fully understood that the present invention, describe technical scheme in detail with instantiation below, but the present invention It is not limited thereto.
Embodiment 1
Described one is used for living paratyphoid vaccine for piglets adjuvant, the following component including by weight: aluminium hydroxide gel 38, phosphorus Acid calcium 30, vitamin e1 5, lentinan 4, lanoline 17.
The preparation method of aluminium hydroxide gel is: by the soda of the Alumen of mass concentration 25%-28% Yu mass concentration 10-12% Solution, is stirred continuously with 60rpm speed, pH value 6.5-6.8 50 DEG C~60 DEG C mixing in temperature, is passed through steam pipe and carries out ripe Change, drive away CO2Make colloidal state thinning, burnt hair, blue or green bright for ripening standard, blow the boiling time to there is no a large amount of bubble, pH7.6~ Between 7.8;Adding cold water makes ripening glue temperature drop to less than 75 DEG C, stirs;Washing after draining mother solution, washing water temperature exists 50~55 DEG C, smash glue salt with splash bar during washing, stir, wash 5-6 time, after checking that sulfate is qualified, stop washing;Make Glue amount moisture content obtains aluminium hydroxide gel when taking off 2~2.5 times to about Alumen inventory.
Described one is used for living paratyphoid vaccine for piglets adjuvant, and preparation method is:
(1) using physiological saline solution aluminium hydroxide gel, aluminium hydroxide gel mass percentage content is 20%;
(2) adding in aluminium hydroxide gel mixed liquor of normal saline by calcium phosphate, vitamin E, lentinan, lanoline, mixing is all Even, adjust pH to make adjuvant to 6.5.
Antigen is added in adjuvant according to the weight ratio of 1:1, according to 3000rpm, emulsifying 30 minutes.
According to national basic veterinary drug standard, verify its result:
Safety verification: with more than 30 ages in days, body weight 12kg, delactational piglets 20, after every ear, superficial muscular vaccinates 1ml. Observe 24 hours, all should have no adverse reaction.After observing 10, all there is not untoward reaction in 20 piglets.
Efficacy test: immune group with more than 30 ages in days, body weight 12kg, delactational piglets 10, superficial muscular note after every ear Penetrating vaccine 1ml, after 30 days, together with the non-immunized controls piglet 5 that condition is identical, intravenous injection digests through meat liver stomach (film) Salmonella choleraesuls (CVCC79102 strain) bacterium solution 2.0ml (containing 1MLD viable bacteria) in 2 generations cultivated by soup.Isolation is raised Support, observe 21, the survival condition of record piglet.
Assay: comparison piglet falls ill entirely, and immune group protective rate is 100%.
Embodiment 2
Described one is used for living paratyphoid vaccine for piglets adjuvant, the following component including by weight: aluminium hydroxide gel 42, phosphorus Acid calcium 28, vitamin e1 2, lentinan 5, lanoline 15.
The preparation method of aluminium hydroxide gel is: by the soda of the Alumen of mass concentration 25%-28% Yu mass concentration 10-12% Solution, is stirred continuously with 60rpm speed, pH value 6.5-6.8 50 DEG C~60 DEG C mixing in temperature, is passed through steam pipe and carries out ripe Change, drive away CO2Make colloidal state thinning, burnt hair, blue or green bright for ripening standard, blow the boiling time to there is no a large amount of bubble, pH7.6~ Between 7.8;Adding cold water makes ripening glue temperature drop to less than 75 DEG C, stirs;Washing after draining mother solution, washing water temperature exists 50~55 DEG C, smash glue salt with splash bar during washing, stir, wash 5-6 time, after checking that sulfate is qualified, stop washing;Make Glue amount moisture content obtains aluminium hydroxide gel when taking off 2~2.5 times to about Alumen inventory.
Described one is used for living paratyphoid vaccine for piglets adjuvant, and preparation method is:
(1) using physiological saline solution aluminium hydroxide gel, aluminium hydroxide gel mass percentage content is 20%;
(2) adding in aluminium hydroxide gel mixed liquor of normal saline by calcium phosphate, vitamin E, lentinan, lanoline, mixing is all Even, adjust pH to make adjuvant to 6.5.
Antigen is added in adjuvant according to the weight ratio of 1:1, according to 3000rpm, emulsifying 30 minutes.
According to national basic veterinary drug standard, verify its result:
Safety verification: with more than 30 ages in days, body weight 12kg, delactational piglets 20, after every ear, superficial muscular vaccinates 1ml. Observe 24 hours, all should have no adverse reaction.After observing 10, all there is not untoward reaction in 20 piglets.
Efficacy test: immune group with more than 30 ages in days, body weight 12kg, delactational piglets 10, superficial muscular note after every ear Penetrating vaccine 1ml, after 30 days, together with the non-immunized controls piglet 5 that condition is identical, intravenous injection digests through meat liver stomach (film) Salmonella choleraesuls (CVCC79102 strain) bacterium solution 2.0ml (containing 1MLD viable bacteria) in 2 generations cultivated by soup.Isolation is raised Support, observe 21, the survival condition of record piglet.
Assay: comparison piglet falls ill entirely, and immune group protective rate is 100%.

Claims (8)

1. one kind be used for living paratyphoid vaccine for piglets adjuvant, it is characterised in that include aluminium hydroxide gel, calcium phosphate, vitamin E, Lentinan, lanoline.
One the most according to claim 1 is used for living paratyphoid vaccine for piglets adjuvant, it is characterised in that include by weight Following component: aluminium hydroxide gel 20-60, calcium phosphate 20-40, vitamin e1 0-20, lentinan 1-10, lanoline 10-30.
One the most according to claim 1 is used for living paratyphoid vaccine for piglets adjuvant, it is characterised in that include by weight Following component: aluminium hydroxide gel 30-55, calcium phosphate 25-35, vitamin e1 2-16, lentinan 2-8, lanoline 15-20.
One the most according to claim 1 is used for living paratyphoid vaccine for piglets adjuvant, it is characterised in that include by weight Following component: aluminium hydroxide gel 38, calcium phosphate 30, vitamin e1 5, lentinan 4, lanoline 17.
One the most according to claim 1 is used for living paratyphoid vaccine for piglets adjuvant, it is characterised in that aluminium hydroxide gel Preparation method is: by the soda ash solution of the Alumen of mass concentration 25%-28% and mass concentration 10-12% in temperature at 50 DEG C~60 DEG C mixing, is stirred continuously with 60rpm speed, pH value 6.5-6.8, is passed through steam pipe and carries out ripening, drive away CO2Make colloidal state thinning, Burnt hair, blue or green bright for ripening standard, blow the boiling time to there is no a large amount of bubble, between pH7.6~7.8;Add cold water and make ripening glue Temperature drops to less than 75 DEG C, stirs;Wash after draining mother solution, washing water temperature at 50~55 DEG C, splash bar during washing Smash glue salt, stir, wash 5-6 time, after checking that sulfate is qualified, stop washing;Glue amount moisture content is made to take off to about Alumen Aluminium hydroxide gel is obtained during 2~2.5 times of inventory.
One the most according to claim 1 is used for living paratyphoid vaccine for piglets adjuvant, it is characterised in that preparation method is:
(1) physiological saline solution aluminium hydroxide gel is used;
(2) adding in aluminium hydroxide gel mixed liquor of normal saline by calcium phosphate, vitamin E, lentinan, lanoline, mixing is all Even, adjust pH to make adjuvant to 6.5.
One the most according to claim 6 is used for living paratyphoid vaccine for piglets adjuvant, it is characterised in that in step (1), uses Physiological saline solution aluminium hydroxide gel, aluminium hydroxide gel mass percentage content is 20%.
One the most according to claim 6 is used for living paratyphoid vaccine for piglets adjuvant, it is characterised in that by antigen according to 1: The weight ratio of 1 adds in adjuvant, according to 3000rpm, emulsifying 30 minutes.
CN201610684088.2A 2016-08-18 2016-08-18 A kind of for living paratyphoid vaccine for piglets adjuvant Pending CN106177942A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109908338A (en) * 2019-02-26 2019-06-21 苏州博特龙免疫技术有限公司 Novel oiliness immunologic adjuvant and preparation method thereof and the application in Antibody preparation

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102245201A (en) * 2008-10-12 2011-11-16 麻省理工学院 Adjuvant incorporation in immunonanotherapeutics
CN102647977A (en) * 2009-10-08 2012-08-22 阿祖瑞博有限公司 Formulation of drugs and vaccines in the form of percutaneous injectable needles
CN102988982A (en) * 2012-12-14 2013-03-27 山东滨州沃华生物工程有限公司 Method for preparing nano aluminum hydroxide gel adjuvant
CN104013955A (en) * 2014-06-18 2014-09-03 中国科学院过程工程研究所 Oil-in-water emulsion free of surfactant and use thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102245201A (en) * 2008-10-12 2011-11-16 麻省理工学院 Adjuvant incorporation in immunonanotherapeutics
CN102647977A (en) * 2009-10-08 2012-08-22 阿祖瑞博有限公司 Formulation of drugs and vaccines in the form of percutaneous injectable needles
CN102988982A (en) * 2012-12-14 2013-03-27 山东滨州沃华生物工程有限公司 Method for preparing nano aluminum hydroxide gel adjuvant
CN104013955A (en) * 2014-06-18 2014-09-03 中国科学院过程工程研究所 Oil-in-water emulsion free of surfactant and use thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109908338A (en) * 2019-02-26 2019-06-21 苏州博特龙免疫技术有限公司 Novel oiliness immunologic adjuvant and preparation method thereof and the application in Antibody preparation

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Application publication date: 20161207