Proteolytic extract from bromelain for the treatment of connective tissue disorders
Inventors
Rosenberg, Lior • Rubin, Guy • Asculai, Eilon
Assignees
Publication Number
US-9511126-B2
Publication Date
2016-12-06
Expiration Date
2032-07-19
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Abstract
The present invention relates to a proteolytic extract obtained from bromelain for the treatment of connective tissue diseases. In particular, the present invention relates to a pharmaceutical composition that includes proteolytic extract obtained from bromelain for the treatment of diseases such as Dupuytren's disease and Peyronie's disease.
Core Innovation
The invention relates to a proteolytic extract obtained from bromelain, a mixture of proteolytic enzymes derived from the stem of the pineapple plant, for the treatment of connective tissue diseases associated with excess collagen deposition. Specifically, it provides a pharmaceutical composition including this proteolytic extract, comprising cysteine proteases such as stem bromelain and ananain, for treating diseases like Dupuytren's disease and Peyronie's disease. The extract demonstrates the ability to degrade native, non-denatured collagen, selectively dissolving diseased fibrous cords or plaques while preserving healthy connective tissue.
The problem addressed by the invention is the lack of safe and effective non-invasive treatments for connective tissue disorders marked by excess collagen, such as Dupuytren's and Peyronie's diseases. Existing treatments, including surgical fasciectomy and collagenase injections, have limitations such as high recurrence rates, potential damage to healthy tissues, complications, and limited efficacy. Prior art does not disclose or suggest that proteolytic enzymes from plant sources like bromelain can treat these diseases effectively without harming healthy tissues.
The invention discloses that a proteolytic extract from bromelain can rupture or dissolve the fibrotic cords characterizing these diseases with specificity to the diseased tissues, offering an improved and safe medication. The extract can be prepared in concentrated small volumes for injection, minimizing extravasation and surrounding tissue damage, thereby simplifying clinical procedures and increasing patient compliance. This marks a novel use of bromelain-derived enzymes for enzymatic fasciotomy and treatment of connective tissue diseases with excess collagen deposition.
Claims Coverage
The patent claims several inventive features focusing on methods and compositions using a proteolytic extract from bromelain for treating connective tissue diseases characterized by excess collagen deposition. The independent claims cover both the method of treatment and the pharmaceutical composition comprising specific cysteine proteases with varied formulations and components.
method of treating connective tissue disease using proteolytic extract from bromelain
Administering to a subject in need a pharmaceutical composition comprising a therapeutically effective amount of a proteolytic extract obtained from bromelain containing at least one cysteine protease selected from stem bromelain EC 3.4.22.32 and ananain EC 3.4.22.31, and at least one cysteine protease precursor, targeting diseases associated with excess collagen deposition.
inclusion of specific connective tissue diseases in treatment
The method applies to connective tissue diseases selected from Dupuytren's disease, Peyronie's disease, frozen shoulder, and Ledderhose disease.
composition comprising specific cysteine proteases and fragments
The proteolytic extract comprises stem bromelain, ananain, at least one cysteine protease precursor, optionally at least one cysteine protease fragment, and a lectin.
pharmaceutical composition additionally comprising anesthetic, antibacterial, and anti-inflammatory agents
The pharmaceutical composition further includes agents selected from anesthetic agents (such as lignocaine, bupivacaine, cocaine), antibacterial agents from a comprehensive list of antibiotics and antimicrobials, and anti-inflammatory agents including both non-steroidal and steroidal varieties.
pharmaceutical composition comprising stabilizing and auxiliary components
The composition can further include components such as stabilizing agents, anti-oxidants, preservatives, buffering agents, chelating agents, and tonicity agents enhancing the formulation.
various pharmaceutical formulations and routes of administration
The pharmaceutical composition can be formulated as solid (powder), semi-solid, liquid—including injectable solutions with pH about 6 to 7—and foam formulations, and is administered preferably by injection into diseased fibrous tissue, either as a single dose or in aliquots at multiple sites.
The claims cover both the method of treating connective tissue diseases involving excess collagen deposition with a bromelain-derived proteolytic extract and the corresponding pharmaceutical compositions. They specify the cysteine proteases involved, the diseases treated, the possible inclusion of auxiliary agents, and the formulation and administration modalities, outlining a comprehensive approach to safe and effective enzymatic therapy.
Stated Advantages
The proteolytic extract selectively degrades diseased fibrous tissue rich in collagen while maintaining healthy connective tissue integrity.
The extract exhibits similar or superior efficacy compared to Clostridium histolyticum collagenase but with higher specificity, reducing potential damage to non-diseased ligaments or tendons.
High concentration preparations in small injectable volumes minimize extravasation and damage to surrounding tissues, simplifying clinical procedures.
The invention provides a safe, efficient, and non-invasive enzymatic medication for treatment of connective tissue diseases involving excess collagen deposition.
Documented Applications
Treatment of Dupuytren's disease characterized by contracture of fingers due to fibrotic cords formed by excess collagen deposition.
Treatment of Peyronie's disease involving fibrous plaques with excess collagen causing penile curvature.
Treatment of frozen shoulder (adhesive capsulitis) associated with fibrosis of joint capsules.
Treatment of Ledderhose disease involving fibrous tissue malformations with excess collagen.
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