Pharmaceutical preparation of recombinant factor VIII lyophilized without albumin as a stabilizer

A coagulation factor, drying technology, applied in the direction of coagulation/fibrinolysis factor, freeze-dried delivery, factor VII, etc., can solve problems such as virus infection

Active Publication Date: 2005-12-28
GREEN CROSS CORP THE
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0023] The object of the present invention is to solve the problem of virus infection that may occur due to albumin derived from human blood, which has been used as a stabilizer of human coagulation factor VIII, and to provide a drug effect compared with the above-mentioned products containing albumin Novel lyophilized recombinant human coagulation factor VIII preparation without albumin

Method used

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  • Pharmaceutical preparation of recombinant factor VIII lyophilized without albumin as a stabilizer
  • Pharmaceutical preparation of recombinant factor VIII lyophilized without albumin as a stabilizer
  • Pharmaceutical preparation of recombinant factor VIII lyophilized without albumin as a stabilizer

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Experimental program
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Effect test

Embodiment 1

[0044] In order to search for a substance that can stabilize recombinant human coagulation factor VIII instead of albumin derived from human blood, lecithin (phosphatidylcholine), sucrose, glycine, PVP (polyvinylpyrrolidone) and amino acid (arginine) were used as stabilizers. amino acid, isoleucine, glutamic acid) to prepare the final stock solution mixture for freeze-drying of each recombinant human coagulation factor VIII, and in order to confirm the activity after freeze-drying, for each prepared recombinant human coagulation factor VIII after freeze-drying The human factor VIII coagulation mixture was tested for activity, cake apperance, and clarity.

[0045] The materials and instruments used are as follows.

[0046] -L-Arginine (M.W.210.7 Sigma)

[0047] -L-Isoleucine (M.W.131.2 Sigma)

[0048] -L-Glutamic acid (M.W.169.1 Sigma)

[0049] -L-Histidine hydrochloride (M.W.209.63 Fluka)

[0050] - Sucrose (M.W. 342.3 Sigma)

[0051] -Tween 80 (Sigma)

[0052] -PEG 3350...

Embodiment 2

[0087] In order to search for the amino acid (arginine, isoleucine, glutamic acid) recombinant human coagulation factor VIII mixture that exhibits optimal conditions as a substitute for the albumin stabilizer as shown in the above-mentioned Example 1 Experiments were conducted on the best conditions for the blocky appearance after freeze-drying, and the experimental results are shown in Table 3 below.

[0088] Exterior

[0089] As shown in Table 3 above, compared with the control sample (containing albumin), the condition of arginine 12-36mM, isoleucine 4-18mM, and glutamic acid 19-57mM showed the best lumpy appearance .

Embodiment 3

[0091] With reference to the results in Table 3 above, among the three amino acids, the concentration of two amino acids was kept constant at the minimum concentration (arginine 12 mM, isoleucine 3.5 mM, glutamic acid 19 mM) to form a block appearance, and in order to Amino acid, isoleucine, glutamic acid each concentration investigation activity change, change the concentration of a kind of amino acid, carry out freeze-drying as above Example 1 and make the recombinant human coagulation factor VIII mixture, and according to chromatographic analysis and Coagulation Assays The activity expressed as % relative to the recombinant human factor VIII coagulation mixture containing albumin was analyzed.

[0092] The concentration of isoleucine and glutamic acid were kept constant at the minimum concentration of 3.5mM and 19mM, which formed a complete block appearance after freeze-drying, and only the concentration of arginine was changed in the range of 6-100mM to evaluate its activit...

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Abstract

Disclosed is a lyophilized preparation of recombinant factor VIII used as a therapeutic preparation of hemophilia A. The lyophilized preparation of recombinant factor VIII is prepared by performing lyophilization using a mixture comprising 6 to 100 mM of L-arginine, 3.5 to 50 mM of L-isoleucine, and 10 to 100 mM of L-glutamic acid as a stabilizer for stabilizing the recombinant factor VIII which exhibits an unstable activity during lyophilization, rather than using human blood derived albumin.

Description

technical field [0001] The present invention relates to a lyophilized recombinant human coagulation factor VIII mixture used as a therapeutic agent for hemophilia A, and more particularly, to a recombinant human coagulation factor VIII as a protein that is unstable during lyophilization A stabilizer that uses amino acids that are not dangerous for virus infection to replace albumin from human blood to stabilize the recombinant human coagulation factor VIII freeze-dried composition that does not contain albumin. Background technique [0002] Hemophilia is a genetic disease in which hemostasis cannot be performed due to a congenital coagulation disorder, which is considered to be caused by the lack of a biologically active coagulation factor, one of the proteins normally present in human plasma. [0003] Hemophilia is a recessive sex-linked genetic disease, so in the case of women, even if they have hemophilia genetic factors, they will not develop the disease, and the disease...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/16A61K9/19A61K38/37A61K47/18C07K14/755
CPCA61K9/19A61K38/37A61K47/183C07K14/755A61P7/00A61P7/04A61K38/16
Inventor 白相勋辛龙男金振晚许在旭李正湜权起圣千知玄
Owner GREEN CROSS CORP THE
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