Abstract: Disclosed herein are compositions and methods for treating uterine fibroids in vivo, and methods of reducing symptoms associated with uterine fibroids, including pain, bleeding and infertility. The disclosed compositions comprise collagenase in an amount effective to cause shrinkage and/or reduce stiffness of uterine fibroids.

Abstract: This invention includes fusogenic compounds, and compositions and methods of use thereof. The fusogenic compounds can be used for making nanoparticle compositions for use in biopharmaceuticals and therapeutics. More particularly, this invention relates to compounds, compositions and methods for providing nanoparticles to incorporate or encapsulate active agents, to deliver and distribute the active agents to cells, tissues, organs, and subjects.

Abstract: This invention includes ionizable compounds, and compositions and methods of use thereof. The ionizable compounds can be used for making nanoparticle compositions for use in biopharmaceuticals and therapeutics. More particularly, this invention relates to compounds, compositions and methods for providing nanoparticles to encapsulate active agents, such as nucleic acid agents, and to deliver and distribute the active agents to cells, tissues, organs, and subjects.

Abstract: This invention includes fusogenic compounds, and compositions and methods of use thereof. The fusogenic compounds can be used for making nanoparticle compositions for use in biopharmaceuticals and therapeutics. More particularly, this invention relates to compounds, compositions and methods for providing nanoparticles to incorporate or encapsulate active agents, to deliver and distribute the active agents to cells, tissues, organs, and subjects.

Abstract: This invention includes fusogenic compounds, and compositions and methods of use thereof. The fusogenic compounds can be used for making nanoparticle compositions for use in biopharmaceuticals and therapeutics. More particularly, this invention relates to compounds, compositions and methods for providing nanoparticles to incorporate or encapsulate active agents, to deliver and distribute the active agents to cells, tissues, organs, and subjects.

Abstract: Non-thermal Atmospheric Plasma (NAP) from a plasma source is mixed with a liquid medium and the resulting compound is applied to the scalp to treat hair loss. The NAP-medium compound may be applied to the surface of the scalp, or produced in situ, or injected into the scalp.

Abstract: Collagenase Clostridium histolyticum (EN3835) is a proteinase that can hydrolyze the triple-helical region of collagen under physiological conditions. EN3835 targets the collagenase structural matrix at the site of injection and does not require systemic exposure. Embodiments include methods of lysing subdermal collagen to treat various conditions such as benign prostatic hyperplasia, tracheal stenosis, subglottic stenosis and scleroderma.

Abstract: This invention relates to novel recombinant botulinum neurotoxins serotype A exhibiting both (i) an increased duration of effect and (ii) a high specific biological activity. These novel recombinant botulinum neurotoxins comprise at least two additional domains consisting of proline, alanine and an additional amino acid residue and at least one amino acid modification which is located at the alpha-exosite or at the beta-exosite of the light chain of the neurotoxin. The invention further relates to novel recombinant single-chain precursor botulinum neurotoxins and compositions comprising the recombinant botulinum neurotoxin with an increased duration of effect and a high specific biological activity.

Abstract: Formulations and methods of treatment are disclosed for prevention and/or treatment of visual loss from age-related macular degeneration. The disclosed formulations include botulinum neurotoxin. The disclosed formulations may be applied to an intraocular or extraocular region of a patient. If applied to an extra ocular region of a patient, the botulinum-based pharmaceutical formulation may then be transported to the intra-ocular region of the patient, allowing the active ingredient(s) to penetrate into the choroid, neuro-retina, and/or retinal pigment epithelium without direct injection into the eye, eliminating risk of retinal detachment, retinal break, retinal hemorrhage, and blindness. The methods described herein allow for increased blood flow to the choroid, which improves removal of metabolites and intra retinal fluid and also serves to arrest, reverse and/or delay early and later stages of age-related macular degeneration.

Abstract: The present invention aims to provide a non-surgical and non-therapeutic (cosmetic) method of dynamic three-dimensional facelift.

Abstract: The disclosure relates to the use of contact lenses for treating ophthalmologic conditions, such as presbyopia, induced myopia, computer vision syndrome, insufficient accommodation, or a condition associated with insufficient accommodation. The contact lens may be selected based on a measured sagittal depth and/or eccentricity of the cornea. When fitted, fluid may accumulate between the cornea of the eye and the contact lens The lens may exhibit a sufficient amount of apical clearance such that when the wearer blinks, the lens moves no more than 1 mm on the eye. The lens and the eye may be structured such that bubbles greater than 0.5 mm in diameter are prevented from forming between the contact lens and the eye. The contact lens may be used in combination with a suitable bioactive agent providing for enhanced visual correction.

Abstract: A method for treating arrhythmia in a patient in need thereof comprises administering botulinum toxin to the patient. Botulinum toxin may be administered by subcutaneous or intradermal injection. The subcutaneous or intradermal injection may be administered to and/or around the vicinity of a trigeminal nerve, a cervical nerve, a thoracic nerve, a lumbar nerve, and/or a sacral nerve of the patient.

Abstract: A dermal image information processing device including a memory; and a hardware component that reads data from the memory and is configured to: acquire dermal image information showing ridge lines in a papillary layer; detect an singular region in a pattern of the ridge lines; detect a position that is furthest away from the singular region; determine a region for collation based on the detected position; and perform collation of the pattern of the ridge lines using only feature points that are included in the region for collation.

Abstract: Methods are disclosed for treating social anxiety disorder, obsessive compulsive disorder, and/or panic disorder in a subject. The methods include administering a therapeutically effective amount of a neurotoxin to a corrugator supercilii and/or a procerus muscle of the subject to cause paralysis of the corrugator supercilii and/or a procerus muscle in the subject, thereby treating PTSD. The neurotoxin can be Botulinum toxin A, such as at a dose of about 20 to about 50 units of Botulinum toxin A.

Abstract: Disorders such as headaches can be treated by administration of a botulinum toxin to a patient suffering therefrom, such as a migraine headache. A combined a fixed site/fixed dose and an optional follow the pain variable dosage and injection site paradigm is disclosed for optimizing clinical effectiveness of botulinum toxin administration for patients suffering headache, particularly chronic migraine.

Abstract: Topical medications to treat the physical effects of bruises and burns. For bruises, the topical medication preferably includes therapeutically effective amounts of vasoconstrictor, such as phenylephrine HCL USP, an anti-inflammatory, such as Arica, and compounding agents. In one embodiment, the compounding agents are a Versabase® gel which includes water, ammonium acryloyldimethyltaurate copolymer, aloe barbadensis leaf juice powder, allatoin, disodium EDTA, methylchloroisothiazolinone and methylisothiazolinone. For burns, the topical medication preferably combines therapeutically effective amounts of an active anti-bacterial compound, such as silver sulfadiazine, an anesthetic, such as lidocaine, and a histamine blocker, such as diphenhydramine, with suitable compounding agents, such as Versabase® gel. Both the anti-bruise and anti-burn medications of the present invention can advantageously be formulated in solutions, lotions, creams, ointments, gels, foams or transdermal patches.

Abstract: 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.

Abstract: A composition for use in treating penile defects, including erectile dysfunction and Peyronie's disease, is provided. The composition includes adipose tissue and stem cells. The stem cells may be derived from adipose tissue. In embodiments the composition includes additional additives such as growth factors, anti-inflammatories, antioxidants, compositions useful for wound healing, and collagenases. Also provided is a method of treating a penile defect in a patient. The method includes providing a composition containing adipose tissue and stem cells, and implanting that composition into a patient in need of treatment for a penile defect. In some embodiments the patient has Peyronie's disease. In other embodiments, the patient has erectile dysfunction.

Abstract: Pharmaceutical compositions that stabilize a Clostridial toxin active ingredient are described. The compositions can be liquid or solid compositions, and comprise a surfactant and an antioxidant. In some embodiments, the compositions comprise a surfactant selected from a poloxamer and a polysorbate; an antioxidant selected from methionine, N-acetyl cysteine, ethylenediaminetetraacetic acid and combinations thereof, and, optionally, a tonicity agent and/or a lyoprotector selected from, for example, trehalose, sucrose.

Abstract: The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Abstract: The present invention provides a method for producing a drug product comprising a combination of highly purified collagenase I and collagenase II from Clostridium histolyticum. The method utilizes an improved medium for the cultivation of Clostridium histolyticum which includes a non-meat-derived (i.e., non-mammalian) peptone or vegetable peptone. The method includes one or more of: (1) reducing glucose content in the meat-free or vegetable-derived media; and (2) increasing the salt concentration in the meat-free or vegetable-derived media. Also provided is a drug product which includes collagenase I and collagenase II at an optimized fixed mass ratio, and which has a purity of greater than at least 95%.

Abstract: 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.

Abstract: Disorders such as headaches can be treated by administration of a botulinum toxin to a patient suffering therefrom, such as a migraine headache. A combined a fixed site/fixed dose and an optional follow the pain variable dosage and injection site paradigm is disclosed for optimizing clinical effectiveness of botulinum toxin administration for patients suffering headache, particularly chronic migraine.

Abstract: A method of treating atrophic cutaneous scarring in humans is claimed. The method involves the topical application of a therapeutic amount of prostaglandin F2-alpha (PGF 2?) or a PGF 2? analog directly to the area of atrophic scarring.

Abstract: Methods and systems for performing laser-assisted surgery on an eye form a layer of bubbles in the Berger's space of the eye to increase separation between the posterior portion of the lens capsule of the eye and the anterior hyaloid surface of the eye. A laser is used to form the layer of bubbles in the Berger's space. The increased separation between the posterior portion of the lens capsule and the anterior hyaloid surface can be used to facilitate subsequent incision of the posterior portion of the lens capsule with decreased risk of compromising the anterior hyaloid surface. For example, the layer of bubbles can be formed prior to performing a capsulotomy on the posterior portion of the lens capsule.

Abstract: Methods are disclosed for treating social anxiety disorder, obsessive compulsive disorder, and/or panic disorder in a subject. The methods include administering a therapeutically effective amount of a neurotoxin to a corrugator supercilli and/or a procerus muscle of the subject to cause paralysis of the corrugator supercilli and/or a procerus muscle in the subject, thereby treating PTSD. The neurotoxin can be Botulinum toxin A, such as at a dose of about 20 to about 50 units of Botulinum toxin A.

Abstract: The present invention provides a method of inducing hair follicle neogenesis in the skin of a subject in need by transplanting the mixture of the skin extract or the composition with epidermal cells or fibroblasts into the subject. The skin extract of the present invention is obtained by mincing and mixing a skin tissue with phosphate buffer solution, thawing the skin tissue after freeze. The composition of the present invention includes at least lumican, galectin-1 and apolipoprotein A-I.

Abstract: The present invention concerns new compositions containing hyaluronic acid or the derivatives thereof in association with the proteolytic enzyme collagenase (and relative pharmaceutical formulations) for the preparation of a dressing for topical treatment of various kinds of wounds, burns of varying depth, pressure sores, vascular ulcers and diabetic foot ulcers as well as for the treatment of hypertrophic and keloid scars.

Abstract: The present invention relates to a pharmaceutical composition and a method for regenerating normal tissue from fibrotic tissue, the pharmaceutical composition and the method employing a collagen-reducing substance. In accordance with the present invention, normal tissue can be therapeutically regenerated from fibrotic tissue.

Abstract: Methods are disclosed for treating social anxiety disorder, obsessive compulsive disorder, and/or panic disorder in a subject. The methods include administering a therapeutically effective amount of a neurotoxin to a corrugator supercilli and/or a procerus muscle of the subject to cause paralysis of the corrugator supercilli and/or a procerus muscle in the subject, thereby treating PTSD. The neurotoxin can be Botulinum toxin A, such as at a dose of about 20 to about 50 units of Botulinum toxin A.

Abstract: The present invention refers to a culture medium and a process for producing proteases with collagenolytic and gelatinolytic activity by bacteria of the genus Clostridium. Particularly, the present invention refers to an animal product-free culture medium for C. histolyticum, characterized by comprising non-animal origin peptones, preferably vegetable peptones, yeast extract and the amino acids cysteine and arginine. The present invention also refers to a process for producing Clostridium histolyticum liquid culture supernatant comprising one or more proteases with collagenolytic and gelatinolytic activity, and pharmaceutical composition comprising as active ingredient the supernatant or the supernatant optionality purified.

Abstract: The invention provides methods for treating primary disorders of mood and affect, including depressive disorders, anxiety and sleep disorders and CNS disorders comprising the administration of a neurotoxin.

Abstract: A method of treating an inflammatory disease is disclosed. The method comprises administering to the subject a therapeutically effective amount of a polypeptide comprising a pro-domain of TNF-alpha converting enzyme (TACE), said polypeptide being devoid of a catalytic domain of said TACE, said polypeptide comprising a modification at a site selected from the group consisting of R58, R56 and K57 which renders said polypeptide resistant to furin degradation said polypeptide being capable of downregulating an activity of TACE, thereby treating the inflammatory disease.

Abstract: Methods are disclosed for treating social anxiety disorder, obsessive compulsive disorder, and/or panic disorder in a subject. The methods include administering a therapeutically effective amount of a neurotoxin to a corrugator supercilli and/or a procerus muscle of the subject to cause paralysis of the corrugator supercilli and/or a procerus muscle in the subject, thereby treating PTSD. The neurotoxin can be Botulinum toxin A, such as at a dose of about 20 to about 50 units of Botulinum toxin A.

Abstract: The invention provides a method for alleviating discogenic pain by administering a therapeutic agent that disrupts neuronal and/or vascular elements in the disc, which is typically a degenerated disc. Disruption of neuronal elements in the disk includes destroying nerve endings without substantially affecting the central body of the nerve, suppressing activation of the nerve endings, and inhibiting the growth of nerve endings into the disk. Disruption of vascular elements includes causing the vascular extensions to retract from the disk, or suppressing the formation of such extensions. The therapeutic agent may be administered locally via an interbody pump, a bolus or a depot, or may be administered systemically.

Abstract: The present invention relates to agonists of Neprilysin and their use in preventing and treating pulmonary vascular remodeling. Also described are diagnostic and screening applications stemming from the inventor's discovery that Neprilysin is expressed at reduced levels in disease tissues.

Abstract: The invention provides compounds, compositions, and methods for the treatment of diseases, disorders, or conditions that are modulated by matrix metalloproteinases (MMPs). The disease, disorder, or condition can include, for example, stroke, neurological disorders, or ophthalmological disorders. The treatment can include administering a compound or composition described herein, thereby providing a prodrug compound that metabolizes to an active MMP inhibitor in vivo. The MMP inhibition can be selective inhibition, for example, selective inhibition of MMP-2, MMP-9, and/or MMP-14. Thus, the invention provides non-mutagenic prodrug compounds of the formulas described herein that result in the inhibition of MMPs upon in vivo administration.

Abstract: Methods for modifying progression of osteoarthritis by local administration of a clostridial derivative, such as a botulinum toxin, to an arthritis-affected site are disclosed herein.

Abstract: A method of treating anxiety disorder comprising the steps of: identifying a subject with one or more symptoms of an anxiety disorder; a botulinum toxin to soft tissues outside the neurocranium using an injection selected from the group consisting of: a transdermal injection; a subcutaneous injection; and a percutaneous injection; and thereby reducing at least one symptom of anxiety disorder.

Abstract: A method of treating major depression comprising the steps of: identifying a subject with one or more symptoms of a depressive disorder; and administering a botulinum toxin to soft tissues outside the neurocranium using an injection selected from the group consisting of: a transdermal injection; a subcutaneous injection; and a percutaneous injection; and thereby reducing at least one symptom of depression.

Abstract: Methods for modification of mechanical properties or a shape of a mammalian tissue, excluding scar, blood clot, fat; including a step of contacting the tissue with an isolated eukaryotic endopeptidase in an amount sufficient to cause a modification of mechanical properties of the tissue or its shape, but insufficient to cause degradation of the tissue's into incohesive parts, and to the use of eukaryotic endopeptidases for use in methods for treatment of the mammalian body.

Abstract: An aqueous composition having increased protein stability is obtained by: a. determining a pH at which the protein has stability at the desired temperature; b. adding to the composition at least one displacement buffer wherein the displacement buffer has a pKa that is at least 1 unit greater or less than the pH of step (a); and c. adjusting the pH of the composition to the pH of step (a); wherein the aqueous composition does not comprise a conventional buffer at a concentration greater than about 2 mM and wherein the conventional buffer has a pKa that is within 1 unit of the pH of step (a).

Abstract: Methods for prolongation of climax time in a patient in need thereof are presented, as are methods for treating premature ejaculation by local administration of a Clostridial neurotoxin, such a botulinum neurotoxin, to the patient, are provided.

Abstract: The invention relates to truncated growth factors and variants thereof. The invention also relates to methods of making and using the truncated growth factors. The invention further relates to compositions including a protease and a growth factor comprising a bone morphogenic protein (BMP) or a variant thereof. The invention also relates to methods of using the composition.

Abstract: There are provided a lyophilized preparation of botulinum toxin without a protein stabilizer derived from animals. The lyophilized preparation of botulinum toxin according to the present invention can maintain an activity of botulinum toxin, and also exhibit excellent long-term storage stability even under conditions of high temperature, which may occur when botulinum toxin is stored, delivered, and processed.

Abstract: 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.

Abstract: A portable neurotoxin injection tray apparatus that includes a vial section with multiple compartments. Each compartment is capable of storing at least one neurotoxin vial or at least one saline vial. The apparatus also includes a dosage compartment with a tilted support member for positioning at least one of the neurotoxin vials in a tilted orientation. Further, the apparatus includes an injection syringe section that includes multiple compartments, where each compartment is designated to store at least one injection syringe filled with a different dosage of neurotoxin.

Abstract: The present invention claims a novel process for the production and purification of microbial collagenase (Microbial Collagenase EC 3.4.24.3) produced by the non-pathogenic aerobic bacterium Vibrio alginolyticus chemovar. iophagus (NCIMB Number: 1 1038, synonym LMG 3418, hereinafter called Vibrio alginolyticus), which said process provides high production levels of collagenase with a stable, reproducible, cheap fermentation process. The collagenase produced from Vibrio alginolyticus according to the process described herein also presents a specific activity superior to that of other microbial collagenases, is stable in aqueous solution, and can be frozen without significant damage.

Abstract: Compositions and methods for the treatment of thrombotic thrombocytopenic purpura are disclosed.

Abstract: Improved efficacy in treatment of gastric disorders with botulinum toxin is obtained using liposomal encapsulated botulinum formulations for topical administration of the botulinum toxin. The liposomes are typically administered in a physiologically acceptable carrier such as saline or phosphate buffered saline by application onto the surface of the tissue within into the gastrointestinal (GI) tract in need of treatment. Preferably, the formulation is applied via a roller, sponge or nozzle that is attached to an endoscope.