Compositions for treating wounds

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.

Description

CROSS REFERENCE TO RELATED APPLICATION[0001]The present application is a continuation of PCT International Application Serial No. PCT / US2015 / 055522, filed Oct. 14, 2014, which claims the benefit of U.S. Provisional Patent Application No. 62 / 063,793 filed on Oct. 14, 2014, the entire contents of which applications are incorporated herein by reference.SEQUENCE LISTING[0002]The instant application contains a Sequence Listing which has been submitted in ASCII format via EFS-Web and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Sep. 1, 2016, is named 50250701301SegList and is 1.27 Kilobytes in size.TECHNICAL FIELD OF THE INVENTION[0003]The present invention relates to compositions and methods useful for treating wounds, and in particular, treating hard to heal wounds, such as lower extremity ulcers in a diabetic patient, venous stasis ulcers, pressure ulcers, severe burns and large surgical wounds such as abdominoplasties and other types of surgical tis...

AI Technical Summary

Benefits of technology

The patent is about an improved formulation of a protein called rhPDGF-BB which is used to treat wounds. This formulation has several advantages over other therapies: it can be applied less frequently, is safer and easier for patients to handle, works better than current therapies, provides a better substrate for cell attachment and vascular ingrowth, contains a higher concentration of rhPDGF-BB, and is more pure and potent. The formulation includes a solution and a matrix where the rhPDGF-BB is entrapped. When this composition is applied to a wound, the rhPDGF-BB is released over time as the matrix is absorbed by the patient's body. This helps to provide sustained delivery of rhPDGF-BB at the wound site and promotes new cell and tissue ingrowth.

Problems solved by technology

One of the most common and serious complications resulting from diabetes is poorly healing wounds that develop most commonly on areas of high pressure on the surface of the foot, such as under the hallux (big toe), metatarsophalangeal joints, the tops and ends of the toes, the middle and sides of the foot and the heel.

Foot ulcers form as a result of nerve damage resulting in a loss of sensation over such pressure points on the foot, which leads to extended microtrauma, breakdown of overlying tissue, and eventual ulceration.

In addition, this loss in sensation can allow minor scrapes or cuts to go without proper treatment and eventually lead to the formation of ulcers.

Once a diabetic foot ulcer (DFU) is formed, treatment can be challenging, particularly in view of the compromised healing environment due to the presence of neuropathy, vascular disease, altered neutrophil function, diminished tissue perfusion and / or defective protein synthesis, all of which often accompany diabetes.

DFUs are a leading cause of amputation.

The longer these wounds remain, the greater the opportunity for them to increase in size and depth and become infected.

As a consequence, these complications result in 80,000 amputations annually in the U.S. alone.

This chronic pathology also severely compromises the overall health of the patient leading to a further downward health spiral of these patients, and additional costs to the health care system; their treatment doubles the cost of care for affected diabetic patients.

Effective DFU healing, however, has not been consistently achieved through this approach, and results can depend heavily on patient compliance.

However, only a small number of these advanced wound-care products have been shown to accelerate DFU healing in prospective, randomized registration trials, and even some of those results have been called into question by other studies.

Despite some favorable results from prospective, randomized registration trials for certain advanced wound-care products, their overall benefits have been disappointing, as evidenced by the continuing high amputation rates.

Such advanced therapies have not resulted in a consistently effective solution to treating DFUs.

In view of their mixed clinical results along with their greater product cost compared to standard therapy, none of these advanced therapies have been widely adopted as a new standard of care for treating DFUs.

Moreover, no one has successfully developed another formulation of Regranex (i.e. rhPDGF-BB) since its FDA approval.

While clinical and non-clinical data support its clinical use, we believe Regranex has a number of limitations including: 1) the need for daily applications to the DFU by the patient, requiring daily wound dressing changes by the patient; 2) the low dosing prescribed in the FDA-approved Instructions for Use, about 0.006 mg (6 μg) per cm2 of wound surface area; 3) often imprecise dosing due to the difficulty the patient experiences in visualizing and applying the gel from a tube (similar to a toothpaste tube) onto the wound which is often located on the bottom of the foot; 4) the need to keep the product refrigerated (about 2-8° C.

); 5) lack of sterility of the Regranex gel; 6) the need for prolonged patient use up to, and potentially exceeding, 140 daily applications over about a five month period; and 7) the use of the carboxymethylcellulose-based (CMC) topical gel which lacks the ability to provide a biological matrix for cellular ingrowth.

Furthermore, Regranex has been only modestly accepted by the medical community as an effective treatment for DFUs.

While experts in the field question the effectiveness of Regranex's active ingredient, rhPDGF-BB, Applicants believe that there are a number of reasons for Regranex's questionable efficacy.

Second, while the gel carrier is biocompatible, we believe it provides no substrate for cell and vascular ingrowth and in fact may be inhibitory to cell growth and migration in the wound thereby potentially slowing the healing process and resulting in suboptimal healing.

(refrigerated) and must be applied daily often to hard to reach anatomical sites, all leading to poor patient compliance; Fourth, although the clinic data showed no difference between the 100 μg / g formulation and the 300 μg / g formulation, Applicants believe that the growth factor in Regranex is at too low of a concentration for optimal cell recruitment and proliferation.

Fifth and finally, despite its commercial use on patients for the past 15 years, the Applicants believe that the growth factor that is included in Regranex is not fully potent.

Clipping also creates new C-terminal sites for further C-terminal truncations and leads to a very complex mixture of isoforms.

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