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Method of stabilizing alkaline phosphatase

A phosphatase, alkaline technology, applied in the field of preparations containing alkaline phosphatase, can solve the problem of freeze-dried products that do not show increased activity

Inactive Publication Date: 2007-03-21
ASAHI KASEI PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, lyophilized products containing human ALP that do not show increased activity after reconstitution in water and are stable for long-term storage have not been reported

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] To a 20 mM POPSO-NaOH buffer solution ( pH 7.5) (1) without BSA, (2) with 1 (w / v)% BSA and (3) with 3 (w / v)% BSA, and inject 2ml of each resulting solution into a vial and freeze-dried. Under each of the above conditions, each lyophilized product was subjected to a temperature acceleration test at 37° C., and then reconstituted with 2 ml of distilled water at weekly measurements to measure ALP activity, and the test lasted up to 4 weeks. The change in the remaining activity of each sample is shown in Table 1. Significant stabilization was observed in the BSA-added system compared to the BSA-free system.

[0027] Table 1

[0028] BSA-free

Embodiment 2

[0030] 3% sucrose, 3% galactose, and 3% lactose were each added to 20 mM BES containing 3% BSA, 0.1 mM zinc chloride, 30 mM valine, and 400 U / L of human liver-derived ALP - In NaOH buffer (pH 7.5), 3 ml of each resulting solution was injected into two vials and lyophilized. Each lyophilized product was reconstituted by adding 3 ml of distilled water to measure ALP activity. The remaining one vial was placed in a 37°C incubator for 1 week. Thereafter, ALP activity was measured in the same manner. As shown in Table 2, the galactose and lactose-added products of the present invention showed higher residual activity than the sucrose-added system.

[0031] Table 2

[0032] 3% sucrose

Embodiment 3

[0034] 5 (w / v)% of galactose, 5 (w / v)% of fructose and 5 (w / v)% of lactose were added to the solution containing 3% BSA, 0.5mM magnesium chloride, 10μM zinc chloride, respectively. and 400 U / L of human liver-derived ALP (No. T-73, produced by Asahi Kasei Co, Ltd.) in 40 mM PIPES-NaOH buffer, and 2 ml of each resulting solution was injected into a vial and freeze-dried. The freeze-drying conditions are: after vacuuming at a freezing temperature of -50°C, main drying at -10°C for 12 hours, re-drying at 20°C for 24 hours, and vacuum sealing. 2 ml of distilled water was added to each lyophilized product to dissolve it to measure the ALP activity of each sweetened product. The remaining vials were placed in a 37°C incubator, and ALP activity was measured by dissolving an aliquot of the product in 2 ml of distilled water weekly for up to 3 weeks. The remaining activity is shown in Table 3, and the activity of the enzyme was 100% immediately after lyophilization. The residual activ...

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PUM

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Abstract

The present invention provides a freeze-dried human-derived alkaline phosphatase-containing preparation which is obtained by freeze-drying and human-derived alkaline phosphatase in the presence of a saccharide selected from the group consisting of galactose, lactose and fructose, and albumin or dextran. The preparation shows no increase in activity after reconstitution in water and can be stored for the long term. Also a method of stabilizing the preparation is provided.

Description

technical field [0001] The present invention relates to a freeze-dried preparation containing alkaline phosphatase for clinical testing. In particular, the present invention relates to methods for stabilizing human alkaline phosphatase in freeze-dried formulations. More specifically, the present invention relates to lyophilized formulations which do not show an increase in activity after reconstitution in water and which can be stored for a long period of time and methods of stabilizing the formulations. Background technique [0002] Alkaline phosphatase (ALP) is known as an enzyme present in plants, animals, microorganisms and the like. For example, they have a wide range of animal sources, such as small intestines of cattle, pigs, rabbits and dogs, as well as kidneys of cattle and pigs, and placenta of humans, and their microbial sources include enzymes derived from Escherichia coli (E. coli). All these enzymes are commercially available. These enzymes have the same fun...

Claims

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Application Information

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IPC IPC(8): C12N9/16C12N9/96
CPCC12N9/16C12N9/96
Inventor 植田成平山利明
Owner ASAHI KASEI PHARMA