FINE PARTICULATE PREPARATION COMPRISING COMPLEX OF NUCLEIC ACID MOLECULE AND COLLAGEN

• US 20090062184A1
• Filed: 03/24/2005
• Published: 03/05/2009
• Est. Priority Date: 03/24/2005
• Status: Abandoned Application

• Current Assignee: Koken Limited, Dainippon Sumitomo Pharma Company Limited (Sumitomo Chemical Company Limited)
• Original Assignee: Koken Limited, Dainippon Sumitomo Pharma Company Limited (Sumitomo Chemical Company Limited)
• Inventors: Maeda, Miho, Kishimoto, Yoshiko
• Application Number:
  US11/909,457
• Publication Number:
  US 20090062184A1
• Time in Patent Office: Days
• US Class Current: 514/1.100
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 38/17 from animals; from humans enzyme inhibitors A61K38/005
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 48/0008 characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition
• CPC Class Codes: A61K 9/1658 Proteins, e.g. albumin, gelatin
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 15/111 General methods applicable to biologically active non-coding nucleic acids
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 2310/351 Conjugate
• CPC Class Codes: C12N 2320/32 Special delivery means, e.g. tissue-specific

Abstract

The present invention relates an additive comprising at least one substance selected from arginine, trometamol, meglumine, lysine, histidine, monoethanolamine, diethanolamine, triethanolamine, succinic acid, citric acid, tartaric acid, lactic acid, and salts thereof, which is useful in the prevention of aggregation of fine particulate complexes of a nucleic acid and collagen, and the production of a preparation comprising particulate complexes of controlled size which is suited for transporting a nucleic acid into cells.

Claims

1. An additive for making a complex of a nucleic acid molecule and collagen in the form of a fine particle of controlled size, which comprises at least one substance selected from arginine, trometamol, meglumine, lysine, histidine, monoethanolamine, diethanolamine, triethanolamine, succinic acid, citric acid, tartaric acid, lactic acid, and salts thereof.

2. The additive according to claim 1, which is used for preparing an aqueous solution of pH 5-9 comprising the additive at a concentration of at least 1%, said aqueous solution being capable of adjusting the size in such a way that at least 70% of particles are not greater than 10 μ

m as fine particles of controlled size.

3. An aqueous solution comprising an additive described in claim 1 above and collagen, which is for making a complex of a nucleic acid molecule and collagen in the form of a fine particle of controlled size.

4. An aqueous solution comprising an additive described in claim 1 and collagen, which is for preparing a fine particulate complex of controlled size of a nucleic acid molecule and collagen by adding the nucleic acid to the aqueous solution.

5. An aqueous solution comprising an additive described in claim 1 for reconstituting a dry formulation comprising a nucleic acid molecule and collagen into a liquid formulation, which is for making a complex of a nucleic acid molecule and collagen in the form of a fine particle of controlled size.

6. An aqueous solution of pH 5-9 comprising an additive described in claim 1 at a concentration of at least 1%, which is capable of adjusting the size in such a way that at least 70% of particles are not greater than 10 μ

m as fine particles of controlled size.

7. A preparation comprising an additive described in claim 1, a nucleic acid molecule and collagen, wherein the nucleic acid molecule is complexed with collagen to form fine particles of controlled size.

8. The preparation according to claim 7, wherein at least 70% of fine particulate complexes of controlled size are not greater than 10 μ

m in size.

9. The preparation according to claim 7 or 8, which is a liquid formulation.

18. The additive according to any one of claims 1, 2 and 10, wherein the collagen is atelocollagen.

10. An additive comprising at least one substance selected from arginine, trometamol, meglumine, lysine, triethanolamine, and salts thereof, which is:

(1) for making a complex of a nucleic acid molecule and collagen in the form of a fine particle of controlled size,

(2) for preventing fine particles from aggregating and allowing fine particles to well disperse in a liquid formulation comprising fine particulate complexes of controlled size of a nucleic acid molecule and collagen, and/or

(3) for maintaining the prevention of aggregation of fine particles and the good dispersibility of the same in a liquid formulation reconstituted from a dry formulation, which liquid formulation comprises a fine particulate complex of controlled size of a nucleic acid molecule and collagen.

11. An aqueous solution comprising an additive described in claim 10 and atelocollagen, which is for making a complex of a nucleic acid molecule and collagen in the form of a fine particle of controlled size.

12. An aqueous solution comprising the additive described in claim 10 for reconstituting a dry formulation comprising a nucleic acid molecule and collagen into a liquid formulation, which is

(1) for making a complex of a nucleic acid molecule and collagen in the form of a fine particle of controlled size, and

(2) for preventing fine particles from aggregating and allowing fine particles to well disperse in a reconstituted liquid formulation comprising fine particulate complexes of controlled size of a nucleic acid molecule and collagen.

13. A preparation comprising an additive described in claim 10, a nucleic acid molecule and collagen, wherein the nucleic acid molecule is complexed with collagen to form a fine particle of controlled size.

14. The preparation according to claim 13, wherein at least 70% of fine particulate complexes of controlled size are not greater than 10 μ

m in size.

15. The preparation according to claim 13 or 14, which is a liquid formulation comprising the additive described in claim 10 and wherein the fine particulate complexes of controlled size of a nucleic acid molecule and collagen are prevented from aggregating and well dispersed.

16. The preparation according to claim 13 or 14, which is a dry formulation comprising the additive described in claim 10, and which gives a liquid formulation by reconstitution wherein the prevention of aggregation of fine particles and the good dispersibility of the same are maintained.

17. The preparation according to any one of claims 7 to 9 and 13 to 16 which is to transporting a nucleic acid molecule into a desired cell.

19. The aqueous solution according to any one of claims 3 to 6, 11 and 12, wherein the collagen is atelocollagen.

20. The preparation according to any one of claims 7 to 9 and 13 to 17, wherein the collagen is atelocollagen.