| Objective：The effect of storage temperature and concentration of protective solution onstability of recombinant human p53adenovirus injection was studied on this paper.Methods: Two kinds of storage style including room temperature storage and repeatedfreezing and thawing was chose for study. The index of product quality included the pH, thevirus particles, virus activity units, ratable activity and inserted p53biological activity. Fiveconcentrations of glycerol as protective solution were chose for-20℃stability test and4℃accelerated stability test. For the study of formulation, compare the quality stability betweenthe lyophilized formulation and water injection.Results: When product was stored at room temperature the results show the pH andbiological activity of p53index decreased slightly, no change in the number of virus particles,virus activity units and significant decline in specific activity, and value lower than thefinished product standard requirements, means it is unqualified. Product freeze-thawing4times, each time the test results show the pH, p53biological activity, the virus activity unitsand specific activity are not found in significant decline, the virus particles did not change onno influence on product quality. For the4different components of protective solution A, B, Cand D, by4℃accelerated stability and-20℃long-term stability tests found that exceptformulation C is not stable at4℃, will be degraded after2months, the other formulations aremore stable. Amount of glycerol in the protection of agents designed four concentrations, forthe long-term testing and accelerated testing. The results show that both the accelerated testand long-term test, the sample pH, virus particles, virus activity units and specific activitywith storage time extension, the downward trend in the concentration of data, that viruscontent and activity decreased, p53increased in the biological activity data, that expression ofp53gene activity also decreased, especially for4℃accelerated test. Glycerol concentration of2.5%and5%decline in product quality, but after3months, sample is unqualified. Moreover,glycerol concentration of10%and15%, the product is quality for5to6months. This result isconsistent with results of accelerated testing product stability. These results show that the higher concentration of glycerol in protective agents, the protective effect is better onrecombinant human p53adenovirus injection. For the two formulations of the same batchbulk, from6months of the test results it seems, two formulations of the indicators are verysimilar. Virus activity, the number of virus particles and the specific activity of the downwardtrend is obvious, but equally very similar, and6months of the indicators are much higher thanthe product of qualified indicators.Conclusion:①Recombinant human p53adenovirus injection in room temperature, thelongest sustained period of limitation for storage is less than24hours, doctors and suppliersin the use and transport, storage process should be to minimize the drug storage time at roomtemperature.②freeze-thaw four times the， quality of products within the basic nosignificant effect, indicating that the products at room temperature and-20℃under theconditions of rapid freezing and thawing, and in less than four times, will not affect theproduct quality, combined with the stability of the product test data show that the product beplaced at4℃for3months under the conditions of quality and stability, combined with thefreeze-thaw test data can guide the doctors and drug dealers in more than occurred duringstorage and transportation special handling of the situation method.③For A, B, C, D fourdifferent components of protective solution, except C, other3kinds of protective solutionhave a better protective effect.④Protective agent optimization results show that addition ofprotective agents in the concentration of glycerol10%or more activity and content of theadenovirus ideal protective effect. Considering the effectiveness and cost of the solutionconcentration is still advisable to take10%of the concentration.⑤The main product fromthe lyophilized quality indicators, namely the number of virus particles and virus activitypoint of view, can be used for freeze-dried formulations of recombinant human p53adenovirus injection formulations. |
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