Water-soluble dry solid containing proteinaceous bioactive substance

• US 4,824,938 A
• Filed: 08/31/1987
• Issued: 04/25/1989
• Est. Priority Date: 06/06/1984
• Status: Expired due to Term

• Current Assignee: Kabushiki Kaisha Hayashibara Seibutsu Kaguku Kenkyujo
• Original Assignee: Kabushiki Kaisha Hayashibara Seibutsu Kaguku Kenkyujo
• Inventors: Miyake, Toshio, Koyama, Shunsaku
• Primary Examiner(s): Schain, Howard E.
• Assistant Examiner(s): Draper, Garnette D.
• Application Number:
  US07/093,089
• Time in Patent Office: 603 Days
• Field of Search: 530/350, 530/351, 530/399, 424/85, 514/2, 514/3, 514/8, 514/23, 435/102, 435/188, 536/1.1
• US Class Current: 530/351
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: C07K 14/485 Epidermal growth factor [EGF], i.e. urogastrone
• CPC Class Codes: C07K 14/505 Erythropoietin [EPO]
• CPC Class Codes: C07K 14/525 Tumour necrosis factor [TNF]
• CPC Class Codes: C07K 14/555 Interferons [IFN]
• CPC Class Codes: C07K 14/59 Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g.hCG [human chorionic gonadotropin]; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
• CPC Class Codes: C07K 14/61 Growth hormone [GH], i.e. somatotropin

Abstract

Proteinaceous bioactive substances (including lymphokine and peptide hormone) in dry solid are extremely stabilized by the presence of the specific polysaccharide mainly composed of repeating maltotriose units. Pullulan, elsinan, and their partial hydrolysates are feasible as the polysaccharide. The weight ratio of the polysaccharide to the substance which effectively stabilizes the latter substance is at least 0.5 on the basis of dry solids. The dry solid is advantageously usable as a test reagent, injection, granule, tablet, suppository or ointment.

Claims

1. A water-soluble dry solid composition, comprising:

one part by weight of a proteinaceous bioactive substance in admixture with at least 0.5 parts by weight of a polysaccharide mainly composed of repeating maltotriose units.

2. The composition in accordance with claim 1, wherein the proteinaceous bioactive substance is a member selected from the group consisting of lymphokine and peptide hormone.

3. The composition in accordance with claim 1, wherein the polysaccharide is a member selected from the group consisting of pullulan, elsinan, their partial hydrolysates, and mixtures thereof.

4. The composition in accordance with claim 1, wherein the molecular weight of the polysaccharide is within the range of 10,000-10,000,000 daltons.

5. The composition in accordance with claim 1, containing between 0.5 and 10,000 parts by weight of said polysaccharide to one part by weight of said proteinaceous bioactive substance.

6. A method for making a water-soluble dry solid composition containing a mixture of one part by weight of a proteinaceous bioactive substance along with at least 0.5 parts by weight of a polysaccharide mainly composed of repeating maltotriose units, said method comprising:

providing an aqueous solution containing one part by weight of said proteinaceous bioactive substance in admixture with at least 0.5 parts by weight of said polysaccharide; and

drying the aqueous solution at a temperature below 30°

C. and reduced pressure to produce said water-soluble dry solid composition.

7. The method in accordance with claim 6, wherein the proteinaceous bioactive substance is a member selected from the group consisting of lymphokine and peptide hormone.

8. The method in accordance with claim 6, wherein the polysaccharide is a member selected from the group consisting of pullulan, elsinan, their partial hydrolysates, and mixtures thereof.

9. The method in accordance with claim 6, wherein the molecular weight of the polysaccharide is within the range of 10,000-10,000,000 daltons.

10. The method in accordance with claim 6, wherein said drying step is effected by freeze-drying.

11. The method in accordance with claim 6, containing between 0.5 and 10,000 parts by weight of said polysaccharide to one part by weight of said proteinaceous bioactive substance.