Debriding composition for treating wounds
Inventors
Asculai, Eilon • GEBLINGER, Dafna • Kleyman, Mery • Bartfeld, Deborah Hanah
Assignees
Publication Number
US-11382958-B2
Publication Date
2022-07-12
Expiration Date
2037-01-30
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Abstract
The present invention relates to debriding compositions in the form of an aqueous gel. Particularly, the present invention relates to a debriding composition comprising a proteolytic enzyme mixture obtained from bromelain present in a dry form, and an aqueous gel carrier, wherein, prior to use, the proteolytic enzyme mixture being admixed with the aqueous gel carrier to form a debriding composition useful for debridement and treatment of c wounds.
Core Innovation
The present invention provides a debriding composition in the form of an aqueous gel comprising a proteolytic enzyme mixture obtained from bromelain in a dry or lyophilized form, a pH adjusting agent, and an aqueous gel carrier containing a cross-linked polymer of acrylic acid, a polar co-solvent such as glycerol, and water. Prior to use, the proteolytic enzyme mixture is admixed with the pH adjusting agent and the aqueous gel carrier to form the debriding composition characterized by a viscosity in the range of about 10,000 to about 45,000 centipoise (cP) and a pH between about 6.0 to about 8.0.
The problem being solved is related to the treatment of chronic or hard to heal wounds that contain eschar and damaged non-viable tissue which must be removed for effective healing. Existing enzymatic debridement agents have limitations including rapid attenuation of enzyme catalytic activity due to low pH, adsorption to wound surfaces or dressings, and inhibition by wound exudate components, resulting in limited stability and efficacy. Surgical and mechanical debridement methods also present limitations such as pain, removal of healthy tissue, expense, and the need for trained personnel.
The invention discloses that aqueous gel formulations with specific viscosity (10,000 to 45,000 cP) comprising 1% to 7% (w/w) proteolytic enzyme mixture from bromelain and a pH adjusting agent effectively penetrate eschar tissue of chronic wounds facilitating rapid and effective enzymatic debridement within days. These compositions are safe, well-tolerated with reduced skin irritation due to the inclusion of a polar co-solvent like glycerol, and maintain optimal enzymatic activity by controlling the pH. Methods of use include applying the composition to chronic wounds such as venous leg ulcers and diabetic lower extremity ulcers with treatment regimens varying in application duration and frequency to achieve complete debridement and promote wound healing.
Claims Coverage
The patent includes 16 claims comprising two independent method claims describing a method for debridement of chronic wounds using a specific debriding composition, with inventive features related to composition constituents, formulation parameters, and treatment regimens.
Debriding composition comprising a dry bromelain proteolytic enzyme mixture and specific carrier formulation
The composition comprises (a) a proteolytic enzyme mixture obtained from bromelain including stem bromelain (EC 3.4.22.32), ananain (EC 3.4.22.31), a cysteine protease precursor, and jacalin-type lectin in a dry or lyophilized form; (b) a pH adjusting agent; and (c) a carrier including a carbomer at about 0.9% (w/w), glycerol at about 10% (w/w), and water.
Formation of a gel with defined viscosity and pH
Prior to use, the proteolytic enzyme mixture is admixed with the pH adjusting agent and the carrier to form a gel having a viscosity of about 15,000 to 25,000 cP and pH ranging from about 6.0 to about 8.0, with the enzyme mixture present at about 1% to 5% (w/w) of the total carrier weight.
Treatment regimen involving application to chronic or hard to heal wounds
Applying the debriding composition to the wound site is performed in a regimen comprising two to up to ten applications, with the composition maintained in contact with the wound for at least about 4 to about 72 hours per application.
Various pH adjusting agent selections
The pH adjusting agent can be selected from sodium phosphate, sodium carbonate, or potassium carbonate; with specific embodiments including anhydrous di-sodium hydrogen phosphate at about 0.25% (w/w).
Target wounds for treatment
The method applies to chronic or hard to heal wounds selected from diabetic ulcers, venous stasis ulcers, arterial insufficiency ulcers, pressure ulcers, post-operative wounds, and post-trauma wounds.
Flexibility in application duration and frequency
The composition can be maintained on the wound for durations such as about 24, 48, or 72 hours per application. Application frequency includes regimens of three times a week for at least a week or until complete debridement/wound closure.
Use of composition to achieve complete wound debridement and/or wound closure
Treatment regimens and contact times are conducted and adjusted to achieve complete wound debridement and/or wound closure in the subject.
The claims cover a method of wound debridement using a specific gel composition with a dry bromelain proteolytic enzyme mixture, defined viscosity and pH characteristics, applied under specified treatment regimens to chronic wounds of various etiologies, with pH adjusting agent choices and carrier formulation contributing to efficacy and safety.
Stated Advantages
Provides rapid and effective enzymatic debridement of chronic or hard to heal wounds within days rather than months required by existing ointments.
Enables better penetration of the proteolytic enzyme mixture into eschar tissue due to optimal gel viscosity and pH control.
Safe and well-tolerated with mild or moderate, transient adverse effects similar to the gel vehicle alone.
Reduced skin irritation due to inclusion of polar co-solvent glycerol in the composition.
Stable enzymatic activity maintained by adjusting pH to a range where enzyme activity is maximal (about pH 6.5 to 8.0).
Uses lower enzyme concentrations with longer application times to achieve effective debridement, allowing dosage flexibility.
Documented Applications
Debridement and treatment of chronic wounds including diabetic lower extremity ulcers, venous leg ulcers, arterial insufficiency ulcers, pressure ulcers, post-surgical wounds, and post-trauma wounds.
Application of the debriding composition on hard to heal wounds to achieve wound bed preparation for subsequent healing or closure.
Use in clinical regimens involving application durations range from 4 hours up to 72 hours per treatment, with multiple applications over a treatment period up to several weeks.
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