Pharmaceutically acceptable fixed-dried human blood platelets

Details Pharmaceutically acceptable fixed-dried human blood platelets Pharmaceutically acceptable fixed-dried human blood platelets

1994-11-28

1997-07-29

Wityshyn, Michael G.

Drug, bio-affecting and body treating compositions

Whole live micro-organism, cell, or virus containing

Animal or plant cell

424532, 435 2, A61K 3518, A61K 3514

Patent

active

056519664

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

The present invention relates to fixed-dried blood platelets suitable for administration to human patients and methods of treating wound tissue by the topical application of fixed-dried platelets.


BACKGROUND OF THE INVENTION

The use of platelet concentrates in transfusion medicine has become well established during the past thirty years. However, the rapid loss of platelet function during the storage period and risk of bacterial contamination has greatly complicated management of an effective inventory of platelet concentrates in blood banks. In many settings, the limited shelf life of platelet concentrates has drastically reduced their usage.
E. Klein et al., J. Pediatrics 49, 517-522 (1956), describe the preparation and administration of lyophilized platelet material to children with acute leukemia and aplastic anemia. Pain and venospasm at the site of infusion were noted. The limited effectiveness of these materials is shown in Table 2 therein. After more than thirty years, these materials have not led to a useful therapeutic treatment.
In order to make platelet transfusion therapy more manageable for blood banks, there has been considerable interest in devising means for diminishing or delaying the loss of platelet function during the storage period. One approach has been in the context of the development of plasma-free storage media. See, e.g., S. Holme, U.S. Pat. No. 4,695,460. Another approach has been to employ biochemical techniques to stabilize the platelets. See, e.g., A. Bode et al., U.S. Pat. No. 4,994,367. While these techniques provide useful extension of shelf life, they do not provide a shelf life extended for prolonged periods of time. Finally, the preparation of platelet membrane microvesicles from, among other things, outdated platelets is described in F. Chao, U.S. Pat. No. 5,185,160.
Fixed-dried blood platelets for use in diagnostic assays are disclosed in U.S. Pat. No. 4,287,087 to Brinkhous et al. While such fixed-dried platelet preparations can be stored for prolonged periods of time for diagnostic purposes, they have not heretofore been provided in a form for human pharmaceutical use. Accordingly, there is a continuing need for new means of preparing blood platelet preparations having prolonged shelf lives which are suitable for administration to human patients.


SUMMARY OF THE INVENTION

A first aspect of the present invention is fixed-dried human blood platelets which, upon reconstitution: (a) adhere to thrombogenic surfaces; (b) do not adhere to non-thrombogenic surfaces; (c) undergo shape change (spreading) upon adhering to a thrombogenic surface; (d) adhere to one another to form a hemostatic plug upon adhering to a thrombogenic surface; and (e) release their granular contents, such as after stimulation and/or spreading (e.g., after receiving a physiological stimulation which would ordinarily cause a metabolically active, live or fresh platelet to release its granular contents, such as contacting wounded tissue).
A second aspect of the present invention is a pharmaceutical formulation comprised of a fixed-dried blood platelets preparation. The fixed-dried blood platelet preparation comprises fixed-dried human blood platelets having the characteristics set forth above.
A third aspect of the present invention is a method of fixing blood platelets to produce fixed-dried blood platelets having the characteristics set forth above, and the platelets so produced. The method comprises contacting the platelets to a fixative such as formaldehyde, paraformaldehyde, glutaraldehyde, or permanganate (e.g., by mixing the platelets with a solution thereof) for a time sufficient to fix or stabilize the platelets but insufficient to cause loss of the characteristics enumerated above. The platelets are then dried to yield fixed-dried blood platelets having the characteristics set forth above.


BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows thrombin generation by platelets of the present invention as compared to fixed-dried platelets of the prior art and unactivated

REFERENCES:
patent: 4145185 (1979-03-01), Brinkhous et al.
patent: 4287087 (1981-09-01), Brinkhous et al.
patent: 4302355 (1981-11-01), Turner, Jr. et al.
patent: 4695460 (1987-09-01), Holme
patent: 4717654 (1988-01-01), Savoca et al.
patent: 4880788 (1989-11-01), Moake et al.
patent: 4994367 (1991-02-01), Bode et al.
patent: 5030560 (1991-07-01), Sinor et al.
patent: 5043261 (1991-08-01), Goodrich et al.
patent: 5059518 (1991-10-01), Kortright et al.
patent: 5151360 (1992-09-01), Handa et al.
patent: 5165938 (1992-11-01), Knighten
patent: 5213814 (1993-05-01), Goodrich, Jr.
patent: 5236716 (1993-08-01), Carmem et al.
patent: 5248506 (1993-09-01), Holme et al.
patent: 5328840 (1994-07-01), Coller
patent: 5344752 (1994-09-01), Murphy
patent: 5358844 (1994-10-01), Stossel et al.
patent: 5376524 (1994-12-01), Murphy et al.
patent: 5378601 (1995-01-01), Gepner-Puszkin
patent: 5428008 (1995-06-01), Chao et al.
J. P. Allain et al; Platelets Fixed With Paraformaldehyde: A New Reagent for Assay of Von Willenbrand Factor and Platelet Aggregating Factor; The Journal of Laboratory and Clinical Medicine 85(2); pp. 318-328 (Feb. 1975).
M. Terasaki et al; Localization of Endoplasmic Reticulum in Living and Glutaraldehyde-Fixed Cells with Fluorescent Dyes; Cell 38, pp. 101-108 (1984).
East Carolina University, Evaluation of Dried Storage of Platelets and RBC for Transfusion: Lyophilization and other Dehydration Techniques, First Year Quarterly Report (1989).
East Carolina University, Evaluation of Dried Storage of Platelets and RBC for Transfusion; Lyophilization and other Dehydration Techniques, First Year, Second Quarterly Report (1989).
M. S. Read et al; Rehydrated Platelets Maintain Hemostatic Properties; The FASEB Journal Abstracts Part II vol. 4(1), issued 29 Feb. 1990.
East Carolina University, Evaluation of Dried Storage of Platelets and RBC for Transfusion: Lyophilization and other Dehydration Techniques, Quarterly Report (Second Quarter, 2nd Year), (1990).
Office of Naval Research, Evaluation of Dried Storage of Platelets and RBC for Transfusion: Lyophilization and other Dehydration Techniques, First Annual Report (1990).
ISBT & AABB 1990 Joint Congress; Stabilization of Platelet Membranes for Lyophilization and Dried Storage, Book of Abstracts S551, (1990).
A. P. Bode, et al., Stabilization of Platelet Membranes for Lyophilization and Dried Storage. American Association of Blood Banks Congress. (1990).
Office of Naval Research; Evaluation of Dried Storage of Platelets and RBC for Transfusion: Lyophilization and other Dehydration Techniques; Second Annual Report, issued 25 Mar. 1991, pp. 1-22.
M. S. Read et al; Studies with Dried and Rehydrated Platelets for Transfusion Products; The FASEB Journal I vol. 5(4); issued 11 Mar. 1991.
L. M. Graham et al; Growth Factor Production Following Prosthetic Graft Implantation; Journal of Vascular Surgery (13(5), pp. 742-744 (May 1991).
S. L. Goodman et al; The effects of substrate-absorbed albumin on platelet spreading; J. Biomater. Sci. Polymer Edn. 2, pp. 147-159 (1991).
A. P. Bode, Evaluation of Dried Storage of Platelets and RBC for Transfusion: Lyophilization and other Dehydration Techniques, Quarterly Report (First Quarter, 3rd Year), (May 1991).
A. P. Bode, Evaluation of Dried Storage of Platelets and RBC for Transfusion; Lyophilization and other Dehydration Techniques, Quarterly Report (Second and Third Quarter, 3rd Year) (1991).
Office of Naval Research; Evaluation of Dried Storage of Platelets and RBC for Transfusion: Lyophilization and other Dehydration Techniques; Third Annual Report, issued 21 Apr. 1992, pp. 1-11.
A. P. Bode, Evaluation of Dried Storage of Platelets and RBC for Transfusion; Lyophilization and other Dehydration Techniques, Quarterly report (Fourth Quarter, 3rd Year), (1992).
R. P. Goodrich, et al. Preservation of metabolic activity in lyophilized human erythrocytes, Proc. Natl. Acad. Sci., 89, pp. 967-971 (1992).
East Carolina University, Evaluation of Dried Storage of Platelets and RBC for Tra

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