The invention relates to recombinant nucleic acid and polypeptides encoding collagenase I and collagenase II, methods for the preparation thereof and methods for the use thereof. The invention also encompasses methods related to releasing a composition comprising collagenase prior to therapeutic administration.

Methods of delivering therapeutic agents by administering compositions including a bacterial collagen-binding polypeptide segment linked to the therapeutic agent to subjects in need of treatment with the therapeutic agent are provided. In these methods, the therapeutic agent is not a PTH/PTHrP receptor agonist or antagonist, basic fibroblast growth factor (bFGF) or epidermal growth factor (EGF). The bacterial collagen-binding polypeptide segment delivers the agent to sites of partially untwisted or under-twisted collagen. Methods of treating collagenopathies using a composition including a collagen-binding polypeptide and a PTH/PTHrP receptor agonist are also provided. In addition, methods of treating hyperparathyroidism, and hair loss using compositions comprising a collagen binding polypeptide and a PTH/PTHrP receptor agonist are provided. Finally, methods of reducing hair regrowth by administering a composition including a collagen binding polypeptide and a PTH/PTHrP receptor antagonist are provided.

The invention relates to compositions and methods for treating uterine fibroids, wherein a uterine fibroid treatment agent comprising collagenase in an amount effective to cause shrinkage of uterine fibroids is injected or inserted into the uterine fibroid.

The present invention is directed to a method of treating or reducing EFP in a patient comprising administering one or multiple low dose injections of collagenase to an area affected by EFP. The invention encompasses methods wherein the dose of collagenase per injection is between about 50 to about 200 ABC units and/or wherein the concentration of collagenase is between about 50 to about 2000 ABC units/milliliter (ml).

Fusion proteins containing active agonist or antagonist fragments of parathyroid hormone (PTH) and parathyroid hormone related peptide (PTHrP) coupled to a collagen-binding domain are presented. The fusion proteins can be used to promote bone growth, to promote hair growth, to prevent cancer metastasis to bone, to promote immune reconstitution with a bone marrow stem cell transplant, to promote mobilization of bone marrow stem cells for collection for autologous stem cell transplant, and to treat renal osteodystrophy. Pharmaceutical agents comprising a collagen-binding polypeptide segment linked to a non-peptidyl PTH/PTHrP receptor agonist or antagonist are also presented.

It is an object of the present disclosure to provide a formulation for injectable collagenase which will have extended residence time for the drug at the therapeutic targeted area for the indication being treated. It is a further object of the disclosure to provide a slow release formulation for collagenase which is compatible with the active ingredient and does not adversely affect its activity. Still a further object of the disclosure is to provide an injectable formulation for collagenase which can be effectively administered to a patient with a small size needle without exhibiting pregelation, which would interfere with the ability to deliver the required dose for treatment.

A pharmaceutical composition based on centella asiatica (Hydrocotyle asiatica L.) for the treatment of lower limb ulcers, including as active ingredients, centella asiatica and sodium acexamate in amounts producing a reciprocal synergistic effect when mixed with at least one adjuvant selected from a healing agent, an antibiotic agent and/or combinations thereof is described.

The invention relates to recombinant nucleic acid and polypeptides encoding collagenase I and collagenase II, methods for the preparation thereof and methods for the use thereof. The invention also encompasses methods related to releasing a composition comprising collagenase prior to therapeutic administration.

Cancer is a significant cause of mortality and morbidity worldwide. One of the principal impediments to the broad success of conventional chemotherapy is poor delivery to and transport within the tumor microenvironment (TME), caused by irregular and leaky vasculature, the lack of functional lymphatics, and underscored by the overproduction of extracellular matrix (ECM) proteins such as collagen. Described herein are engineered Salmonella Typhimurium (S. Typhimurium) bacteria and uses thereof. In some embodiments, the engineered S. Typhimurium bacteria comprises an exogenous collagenase. Also described in exemplary embodiments herein methods of using the engineered S. Typhimurium bacteria, such as part of a,cancer therapy.

Methods and devices for use in reducing the appearance of dimpled skin or other undesirable appearance of skin in a cellulitic region of a patient are provided. The methods include the steps of disrupting fibrous septae located beneath the skin of a cellulitic region and introducing a composition beneath the skin, the composition being effective to reduce or prevent regrowth of the fibrous septae.