Formulations and methods for contemporaneous stabilization of active proteins during spray drying and storage

Patent metadata

Field	Value
Publication number	US-9545379-B2
Application number	US-201514858539-A
Country	US
Kind code	B2
Filing date	Sep 18, 2015
Priority date	Sep 19, 2014
Publication date	Jan 17, 2017
Grant date	Jan 17, 2017

Abstract

A method of treatment of plasma with a physiologically compatible spray dry stable acidic substance (SDSAS) prior to or contemporaneously with spray drying of the plasma that results in greater recovery and greater long-term stabilization of the dried plasma proteins as compared to spray dried plasma that has not be subject to the formulation method of the present invention, as well as compositions related to plasma dried by the methods of the present invention.

First claim

What is claimed is:

1. A method of producing spray dried formulated plasma, the method comprising:
a) providing i) plasma, ii) one or more physiologically compatible spray dry stable acidic substance (SDSAS), wherein said one or more SDSAS is selected from the group consisting of ascorbic acid, citric acid, gluconic acid, glycine hydrogen chloride (glycine-HCl), lactic acid and monosodium citrate, and iii) a spray drying system comprising a spray drier;
b) treating the plasma by adjusting the pH of the plasma with the SDSAS by bringing the concentration of the SDSAS to between about 0.001 and about 0.050 mmol/mL in the plasma to create formulated plasma;
c) drying the formulated plasma with the spray dryer to create spray dried formulated plasma, and determining that the spray dried formulated plasma has a recovery of von Willebrand factor activity at least 5 percentage points greater than the recovery of von Willebrand factor activity obtained from an otherwise identical spray dried plasma that has not undergone treatment with a SDSAS.

2. The method of claim 1 , further comprising reconstituting the spray dried formulated plasma with sterile water to produce reconstituted plasma.

3. The method of claim 2 , wherein said reconstituted plasma has a pH of about 6.8 to about 7.6.

4. The method of claim 1 , wherein said SDSAS is citric acid.

5. The method of claim 1 , wherein said SDSAS is lactic acid.

6. The method of claim 1 , wherein said pH of said plasma is adjusted with said one or more SDSAS up to 30 minutes before drying, thereby creating the formulated plasma.

7. The method of claim 1 , wherein said pH of said plasma is adjusted by adding one or more SDSAS immediately prior to or contemporaneously with drying, thereby creating the formulated plasma.

8. The method of claim 1 , wherein the pH of the plasma is known prior to addition of said SDSAS and the amount of said SDSAS to be added plasma is determined based on the known pH of said plasma.

9. The method of claim 1 , wherein citric acid is added to the plasma to increase citrate concentration by 7.4 mM.

10. The method of claim 1 , wherein said formulated plasma has a pH of about 5.5 to about 6.5.

11. The method of claim 1 , wherein said recovery of von Willebrand factor activity is of about 5 to about 40 percentage points greater than the recovery of von Willebrand factor activity obtained from an otherwise identical spray dried plasma that has not undergone formulation with one or more SDSAS.

12. The method of claim 11 , wherein said recovery of von Willebrand factor activity is of about 10 to about 35 percentage points greater than the recovery of von Willebrand factor activity obtained from an otherwise identical spray dried plasma that has not undergone formulated with one or more SDSAS.

13. The method of claim 1 , wherein said spray dried formulated plasma is stable at ambient temperature for at least 7 days.

14. The method of claim 13 , wherein stability of said spray dried formulated plasma is determined by measuring the activity of Factors V, VII, VIII and IX.

15. The method of claim 1 , wherein said plasma comprises CPD (citrate phosphate dextrose solution) plasma or is WB (whole blood) plasma.

16. A method of producing spray dried plasma, the method comprising:
a) contacting i) blood plasma contemporaneously with ii) one or more spray dry stable acidic substances (SDSAS), wherein said one or more SDSAS is selected from the group consisting of ascorbic acid, citric acid, gluconic acid, glycine hydrogen chloride (glycine-HCl), lactic acid and monosodium citrate, to create a plasma formulation so that the pH of plasma formulation is between about 5.5 and 7.2 and iii) spray drying the plasma formulation;
b) wherein, when reconstituted, the reconstituted plasma formulation is determined to have a recovered amount of active von Willebrand's factor that is greater than that of the same plasma spray dried and reconstituted that has not been contacted with the spray dry stable acidic substance prior to spray drying.

17. The method of claim 16 wherein said reconstituted plasma has a pH of about 6.8 to 7.6.

18. The method of claim 16 wherein the reconstituted plasma has a physiological pH.

19. The method of claim 16 , wherein the reconstitution solution is an alkaline solution.

20. The method of claim 16 , wherein the reconstitution solution comprises a substance selected from the group consisting of: sodium bicarbonate, disodium phosphate, and glycine sodium hydroxide.

Assignees

• Velico Medical Inc

Inventors

• Liu Qiyong Peter
• Cui Junqing
• Lucien Rud Karly
• Carney Ryan
• Sohn Jihae
• Arya Michelle

Classifications

• A61K9/1688 Primary

  resulting in pure drug agglomerate optionally containing up to 5% of excipient · CPC title

• A61K9/16 Primary

  Agglomerates; Granulates; Microbeadlets {; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction (A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51)} · CPC title

• A61K9/1682 Primary

  Processes · CPC title

• F26B3/12

  in the form of a spray {, i.e. sprayed or dispersed emulsions or suspensions (spray drying of solutions B01D1/18)} · CPC title

• F26B3/06

  the gas or vapour flowing through the materials or objects to be dried (F26B3/14 takes precedence) · CPC title