Methods for treating wounds

• US 10,071,182 B2
• Filed: 09/02/2016
• Issued: 09/11/2018
• Est. Priority Date: 10/14/2014
• Status: Active Grant

• Current Assignee: Leslie Wisner-Lynch, Samuel E. Lynch
• Original Assignee: Leslie Wisner-Lynch, Samuel E. Lynch
• Inventors: Lynch, Samuel E., Wisner-Lynch, Leslie
• Primary Examiner(s): Xie, Xiaozhen
• Application Number:
  US15/256,339
• Publication Number:
  US 20170014483A1
• Time in Patent Office: 739 Days
• Field of Search: None
• CPC Class Codes: A61K 38/1858 Platelet-derived growth factor [PDGF]
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 26/0023 Polysaccharides
• CPC Class Codes: A61L 26/0033 Collagen
• CPC Class Codes: A61L 26/0052 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 26/0066 Medicaments; Biocides
• CPC Class Codes: A61L 26/0085 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 26/0095 Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Novel compositions for treating wounds and promoting the healing thereof are described, including composition containing novel combinations of a carrier and recombinant platelet derived growth factor having fewer isoforms and enhanced biostability. Methods of treating wounds with novel therapeutic composition using dosing procedures leading to effective results with a minimal number of treatment applications are also described.

Claims

1. A method of treating a wound that is a chronic ulcer, wherein said method comprises:

(1) debriding the wound to remove necrotic or infected tissue;

(2) forming a therapeutic composition consisting essentially of sterile recombinant human PDGF-BB (rhPDGF-BB) in a physiologic solution and a sterile porous biocompatible carrier, wherein the porous biocompatible carrier is a collagen sponge or collagen wound dressing, and said therapeutic composition is free from an enzyme inhibitor;

(3) applying the therapeutic composition to the wound surface in an amount that is at least about 10 μ

g rhPDGF-BB per cm² of treated wound surface area, wherein the carrier provides a substrate for cell attachment and vascular ingrowth as the wound heals;

(4) covering the wound with a dressing; and

(5) monitoring the healing of the wound during a treatment period and repeating steps (1)-(4) to retreat the wound at treatment intervals of 7 or more days,

(6) wherein the wound is retreated from 2 to 20 times, and wherein each retreatment comprises applying the therapeutic composition to the wound surface in an amount that is at least 10 μ

g rhPDGF-BB/cm² treated wound surface area up to 100 μ

g rhPDGF-BB/cm² treated wound surface area.

2. The method of claim 1 wherein the wound is a chronic ulcer of at least six weeks duration.

3. The method of claim 1 wherein the step of forming the therapeutic composition comprises combining the sterile rhPDGF-BB and the sterile porous biocompatible carrier, wherein:

(i) the sterile rhPDGF-BB comprises an rhPDGF-BB solution comprising between about 0.05 mg/ml to about 5 mg/ml of rhPDGF-BB; and

(ii) the ratio of the rhPDGF-BB solution to the carrier is between about 0.1 ml/cm³ carrier to about 1 ml/cm³ or the ratio of rhPDGF-BB to the carrier is between about 75 μ

g PDGF/cm³ of carrier to about 225 μ

g PDGF/cm³ of carrier.

4. The method of claim 1 wherein the step of forming the therapeutic composition comprises combining the sterile rhPDGF-BB and the sterile porous biocompatible carrier, wherein:

(i) the sterile rhPDGF-BB comprises an rhPDGF-BB solution comprising between about 0.05 mg/ml to about 5 mg/ml of rhPDGF-BB, and

(ii) the ratio of the rhPDGF-BB solution to the carrier is between about 0.25 ml solution/cm³ of carrier to about 5 ml solution/cm³ of carrier, or the ratio of rhPDGF-BB to the carrier is between about 75 μ

g rhPDGF-BB/cm³ of carrier to about 750 rhPDGF-BB/cm³ of carrier.

5. The method of claim 1 wherein at least about 80% of the rhPDGF-BB on a weight basis is unclipped rhPDGF-BB.

6. The method of claim 1 wherein the porous biocompatible carrier is a collagen sponge.

7. The method of claim 1 wherein the porous biocompatible carrier is a collagen wound dressing.

8. The method of claim 1 wherein the cumulative total amount of rhPDGF-BB applied to the wound during the treatment period is less than about 50 mg of rhPDGF-BB.

9. The method of claim 1 wherein the cumulative total amount of rhPDGF-BB applied to the wound during the treatment period is less than about 25 mg of rhPDGF-BB.

10. The method of claim 1 wherein the wound is retreated from 2 to 20 times over a maximum treatment period of 2 to 20 weeks.

11. The method of claim 1 wherein the steps (1)-(4) are repeated to retreat the wound at a retreatment frequency of at least every 8 days.

12. The method of claim 1 wherein the steps (1)-(4) are repeated to retreat the wound at a retreatment frequency of at least every 10 days.

13. The method of claim 1 wherein the wound is retreated a maximum of 10 times.

14. The method of claim 1 wherein:

(A) the wound is a chronic ulcer of at least six weeks duration;

(B) the step of forming the therapeutic composition comprises combining the sterile rhPDGF-BB and the sterile porous biocompatible carrier, wherein;

(i) the sterile rhPDGF-BB comprises an rhPDGF-BB solution comprising between about 0.05 mg/ml to about 5 mg/ml of rhPDGF-BB, wherein at least about 80% of the rhPDGF-BB on a weight basis is unclipped rhPDGF-BB, and

(ii) the ratio of the rhPDGF-BB solution to the carrier is between about 0.1 ml solution/cm³ of carrier to about 1 ml solution/cm³ of carrier, or the ratio of rhPDGF-BB to the carrier is between about 75 μ

g rhPDGF-BB/cm³ of carrier to about 225 μ

g rhPDGF-BB/cm³ of carrier;

(C) the wound is retreated from 2 to 20 times over a maximum treatment period of 2 to 20 weeks at a retreatment frequency of at least every 8 days; and

(D) the cumulative total amount of rhPDGF-BB applied to the wound during the treatment period is less than about 50 mg of rhPDGF-BB.

29. The method of claim 1 wherein when the rhPDGF-BB and the porous carrier are combined, the carrier is capable of entrapping the rhPDGF-BB within its pores such that the rhPDGF-BB is released over time as the carrier is absorbed by the patient'"'"'s body, thereby providing controlled delivery of rhPDGF-BB at the wound over an extended period of time and simultaneously providing a matrix for new cell and tissue ingrowth.

15. A method of treating a wound that is a chronic ulcer, wherein said method comprises:

(1) debriding the wound to remove necrotic or infected tissue;

(2) forming a therapeutic composition consisting essentially of sterile recombinant human PDGF-BB (rhPDGF-BB) in a physiologic solution and a sterile porous biocompatible carrier, wherein the porous biocompatible carrier is a collagen sponge or collagen wound dressing;

(3) applying the therapeutic composition to the wound surface in an amount that is at least about 10 μ

g rhPDGF-BB per cm² of treated wound surface area, wherein the carrier provides a substrate for cell attachment and vascular ingrowth as the wound heals;

(4) covering the wound with a dressing; and

(5) monitoring the healing of the wound during a treatment period and repeating steps (1)-(4) to retreat the wound at treatment intervals of 8 or more days,

wherein the wound is retreated from 2 to 20 times over a maximum treatment period of 2 to 20 weeks, and wherein each retreatment comprises applying the therapeutic composition to the wound surface in an amount that is at least 10 μ

g rhPDGF-BB/cm² treated wound surface area up to 100 μ

g rhPDGF-BB/cm² treated wound surface area.

16. The method of claim 15 wherein the step of forming the therapeutic composition comprises combining the sterile rhPDGF-BB and the sterile porous biocompatible carrier, wherein:

(i) the sterile rhPDGF-BB comprises an rhPDGF-BB solution comprising between about 0.05 mg/ml to about 5 mg/ml of rhPDGF-BB, and

(ii) the ratio of the rhPDGF-BB solution to the carrier is between about 0.1 ml solution/cm³ of carrier to about 1 ml solution/cm³ of carrier, or the ratio of rhPDGF-BB to the carrier is between about 75 μ

g rhPDGF-BB/cm³ of carrier to about 225 μ

g rhPDGF-BB/cm³ of carrier.

17. The method of claim 15 wherein the step of forming the therapeutic composition comprises combining the sterile rhPDGF-BB and the sterile porous biocompatible carrier, wherein:

(i) the sterile rhPDGF-BB comprises an rhPDGF-BB solution comprising between about 0.05 mg/ml to about 5 mg/ml of rhPDGF-BB, and

(ii) the ratio of the rhPDGF-BB solution to the carrier is between about 0.25 ml solution/cm³ of carrier to about 5 ml solution/cm³ of carrier, or the ratio of rhPDGF-BB to the carrier is between about 75 μ

g rhPDGF-BB/cm³ of carrier to about 750 μ

g rhPDGF-BB/cm³ of carrier.

18. The method of claim 15 wherein the cumulative total amount of rhPDGF-BB applied to the wound during the treatment period is less than about 50 mg of rhPDGF-BB.

19. The method of claim 15 wherein the cumulative total amount of rhPDGF-BB applied to the wound during the treatment period is less than about 25 mg of rhPDGF-BB.

20. The method of claim 15 wherein the steps (1)-(4) are repeated to retreat the wound at a retreatment frequency of at least every 10 days.

21. The method of claim 15 wherein the wound is retreated a maximum of 10 times.

22. The method of claim 15 wherein:

(A) the wound is a chronic ulcer of at least six weeks duration;

(B) the step of forming the therapeutic composition comprises combining the sterile rhPDGF-BB and the sterile porous biocompatible carrier, wherein;

(i) the sterile rhPDGF-BB comprises an rhPDGF-BB solution comprising between about 0.05 mg/ml to about 5 mg/ml of rhPDGF-BB, wherein at least about 80% of the rhPDGF-BB on a weight basis is unclipped rhPDGF-BB, and

(ii) the ratio of the rhPDGF-BB solution to the carrier is between about 0.1 ml solution/cm³ of carrier to about 1 ml solution/cm³ of carrier, or the ratio of rhPDGF-BB to the carrier is between about 75 μ

g rhPDGF-BB/cm³ of carrier to about 225 μ

g rhPDGF-BB/cm³ of carrier; and

(C) the cumulative total amount of rhPDGF-BB applied to the wound during the treatment period is less than about 50 mg of rhPDGF-BB.

23. A method of treating a wound that is a chronic ulcer, wherein said method comprises:

(1) debriding the wound to remove necrotic or infected tissue;

(2) forming a therapeutic composition consisting essentially of sterile recombinant human PDGF-BB (rhPDGF-BB) in a physiologic solution and a sterile porous biocompatible carrier, wherein the porous biocompatible carrier is a collagen sponge or collagen wound dressing;

(3) applying the therapeutic composition to the wound surface in an amount that is at least about 10 μ

g rhPDGF-BB per cm² of treated wound surface area, wherein the carrier provides a substrate for cell attachment and vascular ingrowth as the wound heals;

(4) covering the wound with a dressing; and

(5) monitoring the healing of the wound during a treatment period and repeating steps (1)-(4) to retreat the wound at treatment intervals of 10 or more days,

wherein the wound is retreated from 2 to 20 times, and wherein each retreatment comprises applying the therapeutic composition to the wound surface in an amount that is at least 10 μ

g rhPDGF-BB/cm² treated wound surface area up to 100 μ

g rhPDGF-BB/cm² treated wound surface area.

24. The method of claim 23 wherein the step of forming the therapeutic composition comprises combining the sterile rhPDGF-BB and the sterile porous biocompatible carrier, wherein:

(i) the sterile rhPDGF-BB comprises an rhPDGF-BB solution comprising between about 0.05 mg/ml to about 5 mg/ml of rhPDGF-BB, and

(ii) the ratio of the rhPDGF-BB solution to the carrier is between about 0.1 ml solution/cm³ of carrier to about 1 ml solution/cm³ of carrier, or the ratio of rhPDGF-BB to the carrier is between about 75 μ

g rhPDGF-BB/cm³ of carrier to about 225 μ

g rhPDGF-BB/cm³ of carrier.

25. The method of claim 23 wherein the step of forming the therapeutic composition comprises combining the sterile rhPDGF-BB and the sterile porous biocompatible carrier, wherein:

(i) the sterile rhPDGF-BB comprises an rhPDGF-BB solution comprising between about 0.05 mg/ml to about 5 mg/ml of rhPDGF-BB, and

(ii) the ratio of the rhPDGF-BB solution to the carrier is between about 0.25 ml solution/cm³ of carrier to about 5 ml solution/cm³ of carrier, or the ratio of rhPDGF-BB to the carrier is between about 75 μ

g rhPDGF-BB/cm³ of carrier to about 750 μ

g rhPDGF-BB/cm³ of carrier.

26. The method of claim 23 wherein the cumulative total amount of rhPDGF-BB applied to the wound during the treatment period is less than about 50 mg of rhPDGF-BB.

27. The method of claim 23 wherein the cumulative total amount of rhPDGF-BB applied to the wound during the treatment period is less than about 25 mg of rhPDGF-BB.

28. The method of claim 23 wherein the wound is retreated from 2 to 20 times over a maximum treatment period of 2 to 20 weeks.