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Dry heat treatment method for human coagulation factor VIII preparation and dry heat treatment stabilizer

A human blood coagulation factor, dry heat treatment technology, applied in the field of medicine, can solve the problems of human blood coagulation factor VIII titer loss, increase production cost, titer loss, etc., achieve strong operability and controllability, reduce activity loss, The effect of improving the activity recovery rate

Inactive Publication Date: 2012-05-02
SHANGHAI XINXING MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, in the dry heat inactivation process, it was found that without a stabilizer, the titer loss of human coagulation factor VIII is very serious, which may cause up to 50% titer loss
This not only caused a large amount of economic losses, but also increased production costs, so it is necessary to change the formula of human coagulation factor VIII and reduce the loss of potency

Method used

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  • Dry heat treatment method for human coagulation factor VIII preparation and dry heat treatment stabilizer
  • Dry heat treatment method for human coagulation factor VIII preparation and dry heat treatment stabilizer
  • Dry heat treatment method for human coagulation factor VIII preparation and dry heat treatment stabilizer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Example 1: Verification of virus inactivation after adding stabilizer

[0024] (1) Preparation of human coagulation factor VIII

[0025] Centrifuge the plasma at 0-4°C to obtain cryoprecipitate, dissolve the cryoprecipitate, undergo acid precipitation and clarification and filtration, add S / D solution to the final concentration of tween80 1%, TNBP 0.3%, incubate at 24-26°C for 6 hours, and then pass through the column Chromatography obtains a protein solution containing human coagulation factor VIII, and the resulting eluate is dialyzed with a solution containing 0.01-0.1M NaCl, 0.01M trisodium citrate, 0.1%-0.349% lysine hydrochloride, and 0.1%-10% glycine The solution was subjected to ultrafiltration, desalting and dialysis to obtain a concentrated solution of human coagulation factor VIII.

[0026] (2) Add stabilizer to prepare human blood coagulation factor VIII freeze-dried agent

[0027] Add 20% human serum albumin to the concentrated solution to a concentration...

Embodiment 2

[0033] Example 2: The influence of human blood coagulation factor VIII stabilizer on preparations in dry heat inactivation at 80°C for 72 hours

[0034] When preparing the human blood coagulation factor VIII concentrate, the dialysate was concentrated and dialyzed with 0.9% glycine and the prepared stabilizer as the dialysate, and the protection of the stabilizer to the human blood coagulation factor VIII preparation in freeze-drying and dry heat inactivation was observed The recovery rate of potency after lyophilization and dry heat inactivation is as follows:

[0035] Table 2 Human blood coagulation factor VIII stabilizer protection experiment result

[0036]

[0037] It can be seen from Table 2 that when no stabilizer is added and only 0.9% glycine is included as an excipient, the titer loss is as high as 40%-50%, and after adding a stabilizer, the potency loss rate is higher than 90%.

Embodiment 3

[0038] Embodiment 3: human serum albumin and Ca in the dialysate 2+ Protection against human coagulation factor VIII.

[0039] 1. Prepare human coagulation factor VIII according to conventional methods, except CaCl 2 In addition to human albumin, a stabilizer is added according to the standard to prepare a concentrated solution of human blood coagulation factor VIII preparation.

[0040] 2. Observe the clarity of the sample after reconstitution and the activity recovery rate of human coagulation factor VIII

[0041] The concentrated solution prepared by the above method was freeze-dried with the human blood coagulation factor VIII added with the stabilizer as shown in the table below, tested at 80°C for 72 hours, observed the clarity of the solution, and tested the potency to observe the effect of the protective agent on virus inactivation. Effects of human coagulation factor VIII. The results are shown in Table 3.

[0042] Table 3: Research results of the final solution o...

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Abstract

The invention discloses a dry heat treatment method for a human coagulation factor VIII preparation. Before a freeze-drying step, the stabilizer is added into human coagulation factor VIII solution, wherein the stabilizer comprises human serum albumin, Ca2+ soluble salt, amino acid, sodium citrate and sodium chloride; and the concentration percentage of the human serum albumin is 0.5 to 5 percent and the concentration of Ca2+ is 1mmol / L. The invention also discloses the dry heat treatment stabilizer for the human coagulation factor VIII preparation. The dry heat treatment method is performed for 72 hours at 80 DEG C and is effective on both lipid envelop virus and non-lipid envelop virus. Usually, heat treatment is the last step. The method is low in cost and higher in maneuverability and controllability.

Description

technical field [0001] The present invention relates to the technical field of medicine, and more specifically, the present invention relates to a dry heat treatment method and a dry heat treatment method for human blood coagulation factor VIII preparations that can prevent human blood coagulation factor VIII preparations from being inactivated by dry heat for 72 hours at 80°C. Heat treatment stabilizer. Background technique [0002] Human coagulation factor VIII (Human Coagulation Factor VIII), called "antihemophilic globulin", is one of the important components of the endogenous coagulation system in the body. Factor VIII forms a complex with factor IXa, phospholipids, and calcium ions and acts as a cofactor in the activation of factor X. The human blood coagulation factor VIII preparation is a special blood preparation for preventing and treating hemorrhage in type A hemophilia patients. Due to the particularity of blood products, it is easy to carry viruses such as AID...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/37A61K47/42A61P7/04
Inventor 阎晨熊可强
Owner SHANGHAI XINXING MEDICINE
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