A kind of preparation method of non-adjuvant Haemophilus influenzae type b conjugate vaccine freeze-dried agent

Abstract

The invention discloses a preparation method of a non-adjuvant Haemophilus influenzae type b conjugate vaccine freeze-drying agent, which includes formulation, mixture preparation and freeze-drying process. In the process of vacuum freeze-sublimation drying in the freeze-drying process to remove free water, the present invention controls the temperature of the bottled material below the eutectic point of free water and bound water to eliminate the aggregation of CRM197 protein; removes free water by desorption and drying in vacuum During the process, the temperature of the bottled material is controlled below the degradation point to eliminate the degradation of the Hib capsule structure, so that the Haemophilus influenzae type b conjugate vaccine freeze-dried agent does not need to add an adjuvant technical solution, which overcomes the protein aggregation existing in the prior art , structural degradation, and the problems and shortcomings of adding adjuvants, the Haemophilus influenzae type b combined vaccine freeze-dried agent has achieved the purpose of eliminating protein aggregation and structural degradation without adding adjuvants.

Description

technical field [0001] The invention relates to a preparation method of a vaccine freeze-dried preparation, in particular to a freeze-dried preparation of an adjuvant-free Haemophilus influenzae type b conjugate vaccine for making a freeze-dried preparation of Haemophilus influenzae type b conjugate vaccine Preparation. Background technique [0002] Haemophilus influenzae type b conjugate vaccine, scientific name Haemophilus influenzae type b capsular oligosaccharide and CRM197 protein conjugate, also known as Hib-CRM197 protein conjugate, is a vaccine used to prevent influenza type b in children; type b Haemophilus influenzae conjugate vaccine has two dosage forms: freeze-dried preparation and liquid preparation. The two dosage forms are consistent in quality indicators such as polysaccharide content, molecular size and distribution; among them, the freeze-dried preparation has high stability and does not need to add preservatives , and can extend the shelf life and validi...

AI Technical Summary

Problems solved by technology

[0003] Haemophilus influenzae type b conjugate vaccine freeze-dried agent, referred to as type b freeze-dried vaccine; the quality of type b freeze-dried vaccine depends on the freeze-drying process curve, referred to as the freeze-drying process; the freeze-drying process of the prior art makes the prepared type b Aggregation of CRM197 protein in lyophilized vaccines and degradation of Hib capsular structures (ribose-ribitol phosphate polymers), see image 3 and compare figure 1 , so that the biological activity of the b-type freeze-dried vaccine is reduced, so it is necessary to add an adjuvant to the b-type freeze-dried vaccine to enhance the response intensity of the immune receptor; however, the negative effect of the vaccine adjuvant will vary due to different biological receptors different, and an ideal vaccine should not need to add adjuvants; therefore, there are problems and deficiencies in the prior art, such as protein aggregation, structural degradation, and the need to add adjuvants

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