CN104367998B - A kind of preparation method of aluminum hydroxide adjuvant - Google Patents

A kind of preparation method of aluminum hydroxide adjuvant Download PDF

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CN104367998B
CN104367998B CN201410635636.3A CN201410635636A CN104367998B CN 104367998 B CN104367998 B CN 104367998B CN 201410635636 A CN201410635636 A CN 201410635636A CN 104367998 B CN104367998 B CN 104367998B
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aluminum hydroxide
hydroxide adjuvant
added dropwise
solution
temperature
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CN104367998A (en
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艾绪露
薛红刚
陈少华
孙晓艳
胡业勤
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WUHAN INSTITUTE OF BIOLOGICAL PRODUCTS Co Ltd
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WUHAN INSTITUTE OF BIOLOGICAL PRODUCTS Co Ltd
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Abstract

The present invention relates to a kind of compound method of aluminum hydroxide adjuvant, comprise the following steps:(1) aluminum salt solution, aqueous slkali are prepared;(2) aqueous slkali is added dropwise in aluminum salt solution;(3) step (2) reaction product is centrifuged, dissolved again with 0.1 0.5% NaCl solution;(4) reaction mixture washed is heated;(5) wash;(6) sterilizing and packing.

Description

A kind of preparation method of aluminum hydroxide adjuvant
Technical field
The invention belongs to bacterin preparation field, in particular to a kind of preparation method of aluminum hydroxide adjuvant.
Background technology
Aluminium adjuvant is used for long time as immunologic adjuvant, and its security is with immunological enhancement already by people Confirmed.Glenny and its colleague have found aluminium salt (KAl (SO first in nineteen twenty-six4)2·12H2O) it is total to diphtheria toxoid Precipitation, can significantly improve its potency.Present Alum adjuvant mainly has alum, aluminum phosphate, aluminium hydroxide.Wherein hydroxide Aluminium adjuvant is employed the most extensive.
Aluminum hydroxide adjuvant is the boehmite (poorly-crystalline boehmite, PCB) of weak crystal formation, its chemistry Formula AlO (OH), it is inclined aluminium hydroxide.X-ray diffraction show the aluminum hydroxide adjuvants of PCB crystal habits 12.6,27.5, 38.2nd, 48.4 and 64.4 ° of 2 θ has wider characteristic peak to occur.Isoelectric point is to describe a ginseng of aluminum hydroxide adjuvant feature Number, its isoelectric point of the aluminium hydroxide of different commercializations is different,Isoelectric point be 9.5 or so, and Rehydragel LV isoelectric point is 11.6.Aluminum hydroxide adjuvant is into size 1- by many fibrous primary particle agglomerations 10 μm of secondary, the size of this particle play an important role when playing adjuvant immunity effect, and the size of particle can influence Intake of the BMDC to antigen, particle is bigger, and intake effect is poorer.In addition, it is different from《Chinese Pharmacopoeia》It is extensive Professional etiquette is determined,《European Pharmacopoeia》(7.0 editions) are on also including attached ability, sedimentation situation etc. in aluminum hydroxide adjuvant quality control index Parameter of physicochemical properties etc..
Existing 2 big aluminum hydroxide adjuvant manufacturer of the whole world (Brenntag Biosector and General Chemical, That is trade nameWith Rehydragel LV aluminum hydroxide adjuvant) hydrogen-oxygen for meeting above-mentioned parameter can be produced Change aluminium adjuvant, but due to being related to its know-how, do not there is the preparation of its aluminum hydroxide adjuvant of disclosed document and patent report Method.It is therefore, domestic that there is an urgent need to a kind of commercialization aluminum hydroxide adjuvant for approving in the world of industrialized production of being capable of at present Method.
The content of the invention
The present invention relates to a kind of compound method of aluminum hydroxide adjuvant, this method makes the crystalline substance of the aluminum hydroxide adjuvant made The physicochemical property such as volume morphing, particle size, isoelectric point, adsorption capacity parameter is consistent with the commercialization adjuvant approved in the world.
The collocation method of aluminum hydroxide adjuvant of the present invention comprises the following steps:
(1) aluminum salt solution, aqueous slkali are prepared;
(2) aqueous slkali is added dropwise in aluminum salt solution, 50-70 DEG C of keeping temperature during dropwise addition, is added dropwise to certain pH During value, invariable in the pH value by the way that alkaline solution and aluminum salt solution maintenance reaction system are added dropwise simultaneously, constant pH is added dropwise Continue 30~60min, then stop that aluminum salt solution is added dropwise, continue that aqueous slkali is added dropwise to pH value of reaction system compared to constant dropwise addition When pH value lifting 0.8~1.7 be reaction end;
(3) step (2) reaction product is centrifuged, washed with 0.1-0.5% NaCl solution, then with 0.1-0.5%'s NaCl solution dissolves again;
(4) reaction mixture washed is heated to 60-100 DEG C of the first temperature, is stirred and is added dropwise in heating process 0.1-4% NaOH solution regulation pH value is untill 5.8-7.0 and stabilization, due to having aluminium hydroxide during pH is adjusted Crystal structure change, so as to cause pH value to reduce always, therefore it is required that be added drop-wise to final pH not change (this again When be that structure is basicly stable) untill, at such a temperature be heat-treated 1-5 hours, then raise temperature to 110~150 DEG C of heat of second temperature Processing 1~43 hour;
(5) wash:Product after heat treatment is centrifuged, washed 1-3 times with the sodium chloride solution containing 0.1-0.5%, And dissolved again with 0.1-0.5% sodium chloride;
(6) sterilizing and packing:Using moist heat sterilization, sterilized 30 minutes at 121 DEG C, then in an aseptic environment keep 60~ Dispensed after being filtered at 80 DEG C with 50-150 micron membrane filters.
In collocation method of the present invention,
Aluminium salt can be AlCl3 or Al2 (SO4) 3 in step (1), and alkali can be NaOH or ammoniacal liquor, preferably AlCl3 with NaOH solution is reacted, and Al2 (SO4) 3 reacts with ammonia spirit;
The concentration of described aluminium salt is 0.01-1M, and the concentration of aqueous slkali is 0.01-1M;
Described aluminum salt solution is most preferably aluminium composition 0.25mol/L AlCl36H2O solution;
Described aqueous slkali is preferably 0.265mol/L NaOH solution;
Certain pH value scope described in step (2) is 2.5~4.5, preferably 3.0-4.0, after constant pH is added dropwise, Continue be added dropwise aqueous slkali to pH value of reaction system compared to constant dropwise addition when pH value lifting 0.8 be reaction end;
Described solution is added dropwise and is preferably added dropwise by peristaltic pump, and the temperature of reaction system is preferably 60 DEG C;
Step (3) washing is to be washed 1~3 time using 0.3% (wt) NaCl solution, is less than to free aluminium content Untill the 5% of total aluminium content, it is preferred that wash untill free aluminium content is less than the 1% of total aluminium content.
The first temperature described in step (4) is preferably 80 DEG C, and heat treatment time is preferably 3h at the first temperature, described Second temperature is preferably 120 DEG C, and the time being heat-treated at the second temperature is preferably 4h, and described pH adjusting agent is preferably 0.4% NaOH solution;
Washing described in step (5) is preferably to be to sodium chloride concentration by washing of precipitate using 0.1% sodium chloride Untill 0.1%-0.5%, the described sodium chloride that concentration is 0.25% that is dissolved as dissolves again.
Filtering described in step (6) is preferably at 70 DEG C, is filtered with 100 microns of worry film.
Technical scheme of the present invention has the beneficial effect that:Crystal type is PCB;Granular size is distributed in 1-10 μ mostly M, and it is homogeneous, without visible lumpy precipitate;Adsorption capacity is high;Isoelectric point between 9-12, these features with it is general in the world Commercialization aluminum hydroxide adjuvant is basically identical.
Brief description of the drawings
Fig. 1 is the x-ray diffraction pattern that aluminum hydroxide adjuvant is prepared in embodiment 1.
Fig. 2 is the granular size figure that aluminum hydroxide adjuvant is prepared in embodiment 1.
Embodiment
The present invention provides a kind of compound method of aluminum hydroxide adjuvant, and this method is last using a series of technical step Obtained aluminum hydroxide adjuvant physicochemical property is consistent with the commercialization adjuvant approved in the world.
The preparation of the aluminum hydroxide adjuvant of embodiment 1.
(1) weigh AlCl36H2O to be dissolved in water for injection, be configured to aluminium composition 0.25mol/L aluminum salt solution. Weigh NaOH to be dissolved with water for injection, be configured to the aqueous slkali that NaOH content is 0.265mol/L.
(2) first aluminum salt solution being added in reactor, adds 2 times of volume injection water, unlatching is uniformly mixed, Temperature is raised to 60 DEG C.Aqueous slkali is added dropwise with peristaltic pump, when being added drop-wise to pH4.0, while aluminum salt solution is added dropwise, by adjusting aluminium The rate of addition of salting liquid, pH is set to keep constant.Constant pH, which is added dropwise, lasts about 40min, stops that aluminum salt solution is added dropwise, continues to be added dropwise Aqueous slkali is to pH4.8.
(3) will be washed 1 time with isometric 0.3% sodium chloride solution after above-mentioned solution centrifugal, and with 0.3% sodium chloride Solution dissolves precipitation again.The NaCl and purpose dissolved is to remove free aluminium ion, and keep certain ion strong Degree.
(4) adjust temperature to 80 DEG C, be added dropwise 0.4% NaOH regulation pH, until pH is kept between 5.8-7.0 stably, 80 DEG C of heat treatment 3h are kept, are changed to 120 DEG C of heat treatment 4h.
(5) cool down, centrifuge, washing precipitation 1 time with containing 0.1% sodium chloride solution, finally being entered with 0.25%NaCl solution Row weight is molten.0.25%NaCl solution can provide the basic ionic strength of long-time storage.
(6) kept for 70 DEG C after sample of the weight after molten is sterilized, obtained in an aseptic environment by 100 microns of filter membrane sterile Uniform aluminum hydroxide adjuvant.
The preparation of the aluminum hydroxide adjuvant of embodiment 2.
(1) weigh AlCl36H2O to be dissolved in water for injection, be configured to aluminium composition 0.25mol/L aluminum salt solution. Weigh NaOH to be dissolved with water for injection, be configured to the aqueous slkali that NaOH content is 0.265mol/L.
(2) first aluminum salt solution being added in reactor, adds 2 times of volume injection water, unlatching is uniformly mixed, Temperature is raised to 60 DEG C.Aqueous slkali is added dropwise with peristaltic pump, when being added drop-wise to pH3.5, while aluminum salt solution is added dropwise, by adjusting aluminium The rate of addition of salting liquid, pH is set to keep constant.Constant pH, which is added dropwise, lasts about 35min, stops that aluminum salt solution is added dropwise, continues to be added dropwise Aqueous slkali is to pH4.5.
(3) will be washed 1 time with the sodium chloride solution of 2 times of volumes 0.3% after above-mentioned solution centrifugal, and with 0.3% chlorination Sodium solution dissolves precipitation again.
(4) adjust temperature to 80 DEG C, be added dropwise 0.4% NaOH regulation pH, until pH is kept between 5.8-7.0 stably, 80 DEG C of heat treatment 3h are kept, are changed to 120 DEG C of heat treatment 4h.
(5) cool down, centrifuge, washing precipitation 1 time with containing 0.1% sodium chloride solution, finally being entered with 0.25%NaCl solution Row weight is molten.
(6) kept for 70 DEG C after sample of the weight after molten is sterilized, obtained in an aseptic environment by 100 microns of filter membrane sterile Uniform aluminum hydroxide adjuvant.
The preparation of the aluminum hydroxide adjuvant of embodiment 3.
(1) weigh AlCl36H2O to be dissolved in water for injection, be configured to aluminium composition 0.25mol/L aluminum salt solution. Weigh NaOH to be dissolved with water for injection, be configured to the aqueous slkali that NaOH content is 0.265mol/L.
(2) first aluminum salt solution being added in reactor, adds 2 times of volume injection water, unlatching is uniformly mixed, Temperature is raised to 60 DEG C.Aqueous slkali is added dropwise with peristaltic pump, when being added drop-wise to pH3.5, while aluminum salt solution is added dropwise, by adjusting aluminium The rate of addition of salting liquid, pH is set to keep constant.Constant pH, which is added dropwise, lasts about 40min, stops that aluminum salt solution is added dropwise, continues to be added dropwise Aqueous slkali is to pH5.2.
(3) will be washed 1 time with the sodium chloride solution of 0.5 times of volume 0.3% after above-mentioned solution centrifugal, and with 0.3% chlorine Change sodium solution and dissolve precipitation again.
(4) adjust temperature to 80 DEG C, be added dropwise 0.4% NaOH regulation pH, until pH is kept between 5.8-7.0 stably, 80 DEG C of heat treatment 3h are kept, are changed to 120 DEG C of heat treatment 4h.
(5) cool down, centrifuge, washing precipitation 1 time with containing 0.1% sodium chloride solution, finally being entered with 0.25%NaCl solution Row weight is molten.
(6) kept for 70 DEG C after sample of the weight after molten is sterilized, obtained in an aseptic environment by 100 microns of filter membrane sterile Uniform aluminum hydroxide adjuvant.
The aluminum hydroxide adjuvant physical and chemical parameter of embodiment 4. detects
The physical and chemical parameter of aluminum hydroxide adjuvant obtained by above-described embodiment 1-3 is detected,
(1) using the crystal habit of X-ray diffraction measure aluminum hydroxide adjuvant;
(2) surface charge of Zeta potential analysis-e/or determining sample is used, so as to calculate the isoelectric point of aluminium hydroxide;
(3) with Malvern laser particle size analyzer EPA2000 measure granular sizes;
(4) the measure reference of adsoptivity and sedimentation situation《European Pharmacopoeia》(7.0 editions)
Every physical and chemical parameter testing result of the aluminum hydroxide adjuvant of above-described embodiment 1~3 is as shown in table 1 below
1. each embodiment of table and commercially available import aluminum hydroxide adjuvant physical and chemical parameter
Note 1., unit:mgBSA/mgAl
Finally it should be noted that above example is only used for explaining the essence of the present invention, it is not intended as protecting the present invention Protect the restriction of scope.

Claims (9)

1. a kind of collocation method of aluminum hydroxide adjuvant, it is characterised in that comprise the following steps:
(1) aluminium composition 0.25mol/L AlCl is prepared3·6H2O aluminum salt solution, 0.265mol/L NaOH aqueous slkalis;
(2) aqueous slkali is added dropwise in aluminum salt solution, 60 DEG C of keeping temperature during dropwise addition, when being added dropwise to certain pH value, institute The certain pH value stated is any one point value between 3.0~4.0, remains anti-by the way that alkaline solution and aluminum salt solution are added dropwise simultaneously Answer system invariable in the pH value, constant pH, which is added dropwise, continues 30~60min, then stops that aluminum salt solution is added dropwise, continues to drip Add aqueous slkali to pH value of reaction system compared to constant dropwise addition when pH value lifting 0.8~1.7 be reaction end;
(3) step (2) reaction product is centrifuged, washed with 0.1-0.5% NaCl solution, then use 0.1-0.5% NaCl Solution dissolves again;
(4) reaction mixture washed is heated to 60-100 DEG C of the first temperature, is stirred in heating process and 0.1- is added dropwise 4% NaOH solution regulation pH value is heat-treated 3 hours untill 5.8-7.0 and stabilization, then raises temperature to second at such a temperature 110~150 DEG C of temperature is heat-treated 4 hours;
(5) wash:Product after heat treatment is centrifuged, is washed 1-3 times, is used in combination with the sodium chloride solution containing 0.1-0.5% 0.1-0.5% sodium chloride dissolves again;
(6) sterilizing and packing:Using moist heat sterilization, sterilized 30 minutes at 121 DEG C, then keep 60~80 DEG C in an aseptic environment It is lower filtered with 50-150 micron membrane filters after dispense.
2. the collocation method of aluminum hydroxide adjuvant according to claim 1, it is characterised in that in step (2), described is molten Drop adds as being added dropwise by peristaltic pump.
3. the collocation method of aluminum hydroxide adjuvant according to claim 1, it is characterised in that in step (3), the washing The NaCl solution for being 0.3% for use quality content is washed 1~3 time, and be less than total aluminium content to free aluminium content 5% is Only.
4. the collocation method of aluminum hydroxide adjuvant according to claim 3, it is characterised in that washing to free aluminium content Less than total aluminium content 1% untill.
5. the collocation method of aluminum hydroxide adjuvant according to claim 1, it is characterised in that in step (4), described One temperature is 80 DEG C, and described second temperature is 120 DEG C, and described 0.1-4% NaOH solution is 0.4% NaOH solution.
6. the collocation method of aluminum hydroxide adjuvant according to claim 1, it is characterised in that in step (5), described washes Wash for using 0.1% sodium chloride by washing of precipitate untill sodium chloride concentration is 0.1%-0.5%, described is dissolved as using The sodium chloride that concentration is 0.25% dissolves again.
7. the collocation method of aluminum hydroxide adjuvant according to claim 1, it is characterised in that in step (6), described mistake Filter at 70 DEG C, to be filtered with 100 microns of filter membrane.
8. the aluminum hydroxide adjuvant product prepared by any described methods of claim 1-7.
9. application of the aluminum hydroxide adjuvant as immunologic adjuvant described in claim 8.
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CN105125409A (en) * 2015-07-17 2015-12-09 北京海合天科技开发有限公司 Medicine production equipment and method capable of improving yield
CN107998387A (en) * 2017-12-06 2018-05-08 周柳青 A kind of medical porous Al (OH)3The preparation method and applications of adjuvant
CN108066759B (en) * 2017-12-22 2023-01-13 北京民海生物科技有限公司 Aluminum hydroxide adjuvant and preparation method and application thereof
CN109395075A (en) * 2018-11-01 2019-03-01 大连理工大学 AlOOH nano adjuvant with controllable crystallinity and preparation method thereof
CN109432417A (en) * 2018-11-01 2019-03-08 大连理工大学 AlOOH nano adjuvant with controllable length-diameter ratio and preparation method thereof
CN112569350B (en) * 2019-09-30 2024-02-09 成都迈科康生物科技有限公司 Aluminum hydroxide adjuvant and preparation method and application thereof
CN111000996A (en) * 2019-12-27 2020-04-14 深圳康泰生物制品股份有限公司 Aluminum hydroxide adjuvant and preparation method and application thereof
CN111175348A (en) * 2019-12-27 2020-05-19 深圳康泰生物制品股份有限公司 Detection method of isoelectric point of aluminum hydroxide adjuvant and its application in vaccine preparation
CN111643662A (en) * 2020-07-01 2020-09-11 大连理工大学 Hydroxyl alumina nano adjuvant synthesized based on fully mixed flow model and synthetic method thereof
CN113559255B (en) * 2021-07-30 2024-10-18 成都生物制品研究所有限责任公司 Preparation method of aluminum hydroxide adjuvant
CN113666404B (en) * 2021-09-23 2023-07-28 北京智飞绿竹生物制药有限公司 Preparation method of high-concentration nanoscale aluminum hydroxide adjuvant suitable for large-scale production

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102583460A (en) * 2011-01-12 2012-07-18 国家纳米科学中心 Aluminium adjuvant as well as preparation method and application thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102583460A (en) * 2011-01-12 2012-07-18 国家纳米科学中心 Aluminium adjuvant as well as preparation method and application thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
aluminum adjuvants: preparation, application, dosage, and formulation with antigen;Erik B. Lindblad;《methods in molecular biology》;20101231;摘要、第42页第3段、第46页2.1.1、第48页3.1.1 *
氢氧化铝佐剂氨水法配置工艺优化;胡高翔等;《生物技术世界》;20140731;摘要、第64页左栏第1段、第64-65页1.2.1、1.2.4、1.3,第65页右栏第1段 *

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