503 results about "Hyaluronidase" patented technology

The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGPs), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. The invention further comprises sialated and pegylated forms of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.

The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGPs), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. The invention further comprises sialated and pegylated forms of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.

The present invention relates to a highly concentrated, stable pharmaceutical formulation of a pharmaceutically active anti-HER2 antibody, such as e.g. Trastuzumab (HERCEPTIN™), Pertuzumab or T-DM1, or a mixture of such antibody molecules for subcutaneous injection. In particular, the present invention relates to formulations comprising, in addition to a suitable amount of the anti-HER2 antibody, an effective amount of at least one hyaluronidase enzyme as a combined formulation or for use in form of a co-formulation. The formulations comprise additionally at least one buffering agent, such as e.g. a histidine buffer, a stabilizer or a mixture of two or more stabilizers (e.g. a saccharide, such as e.g. α,α-trehalose dihydrate or sucrose, and optionally methionine as a second stabilizer), a nonionic surfactant and an effective amount of at least one hyaluronidase enzyme. Methods for preparing such formulations and their uses thereof are also provided.

The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGPs), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. The invention further comprises sialated and pegylated forms of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.

The present invention concerns a composition for retarding skin aging which contains an edible herb medicine or medicines round in Taiwan, in particular a plant extract or extracts having melanine formation-unhibiting, elastase-inhibiting, hyaluronidase-inhibiting, active oxygen-eliminating and / or radical-capturing type antioxidant activities, and a medicinally acceptable base and / or additives for external dermal application. The composition is useful in promoting skin whitening effects, maintaining the tension and elasticity of the skin, facilitating skin moistening and providing the skin with anti-inflammatory and / or anti-allergic properties.

The invention is based on the discovery of methods for purification of an acid active hyaluronidase found in human plasma (hpHAse), including both biochemical and immunoaffinity purification methods. The method of immunoaffinity purification of the invention is based on the discovery of a method for identifying antibodies that specifically bind native hpHAse (anti-native hpHAse antibodies), and anti-native hpHAse antibodies identified by this screening method. The invention also features an assay for sensitive detection of HAse activity using biotinylated hyaluronic acid (bHA). Purification and characterization of hpHAse lead to the inventors' additional discovery that hpHAse is encoded by the LuCa-1 gene, which gene is present in the human chromosome at 3p21.3, a region associated with tumor suppression. The invention additionally features methods of treating tumor-bearing patients by administration of hpHAse and / or transformation of cells with hpHAse-encoding DNA.

The present invention provides a tnaluronidase. The hyaluronidase can be produced by the strain Streptomyces aitinocidm 77, Exemplary characteristics of the hyaluronidase include specific C-terminal or other amino acid sequences, including full-length sequences, and improved physico-chemical and actix itj properties as compared to known h> alυronidase preparatkiiis. Described are also various uses of the hyaiurυnidasc, including topical administration of the h> aiuronidasc to improve skin penetration of a co-administered active substance.

The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGP's), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. The invention further comprises sialated and pegylated forms of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.

Disclosed are compositions and methods for their use that can be used in cosmetic applications. The composition can include an effective amount of a Centella asiatica stem cells to reduce the activity of hyaluronidase in skin, an effective amount of tetradecyl aminobutyroylvalylamino butyric urea trifluoroacetate or Alpinia galanga leaf extract to promote the production of hyaluronic acid in skin, an effective amount of tripeptide-1 to promote the production of fibronectin and laminin in skin, and a dermatologically acceptable vehicle.

The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGP's), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. The invention further comprises sialated and pegylated forms of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.

The invention relates to a preparation method of cross-linking hyaluronic acid microgel for tissue filler; wherein, the monolithic gel is generated by the cross-linking reaction of the hyaluronic acid and the di-epoxide in the certain mold and processed by acid solution; the purification and dialysis by physiological balanced solution are processed; the microgel is made by extrusion of mechanical equipment. The cross-linking hyaluronic acid microgel has the advantages of (1) specific physical properties that the storage modulus (G') is 500-2000Pa, the loss modulus (G'') is 50-200Pa, the phase angle (Delta) is below 20 and the complex viscosity (Eta*) is 10-3500Pa x s as described by the dynamic viscoelasticity at frequency of 0.05-10Hz, (2) good stability that the performance of gel is independent of high pressure-high temperature treatment and the enzymolysis-resistant performance is excellent, (3) injectable property that the size of fine particle is 50-1000Mum, (4) good biocompatibility of no cytotoxicity, (5) biodegradability of being fully degraded by hyaluronidase, and (6) being suitable for tissue filler and bio-medical treatment.

This application is a continuation-in-part of pending U.S. patent application Ser. No. 10 / 065,995 by the authors, filed on Dec. 9, 2002, for a Commercial Process for Isolation and Purification of Glabridin with High Tyrosinase Inhibitory Activity and its Cosmetic Compositions and Methods Of Use. The current invention discloses the use of Glabridin containing Licorice extract (4-90% Glabridin) as metalloprotease and hyaluronidase inhibiting component in cosmetic topical or oral formulations. These extracts and particularly Glabridin, are useful in anti-wrinkle and anti-aging products, providing elasticity, firmness, tone and texture to the skin, ameliorating fine lines and crows feet in under eye preparations, and prevent skin and hair damage due to UV rays, inflammation and itch, diaper rashes in baby products, as massage or toning oils or emulsion for babies.

The present invention relates to a highly concentrated, stable pharmaceutical formulation of a pharmaceutically active anti-HER2 antibody, such as e.g. Trastuzumab (HERCEPTIN™), Pertuzumab or T-DM1, or a mixture of such antibody molecules for subcutaneous injection. In particular, the present invention relates to formulations comprising, in addition to a suitable amount of the anti-HER2 antibody, an effective amount of at least one hyaluronidase enzyme as a combined formulation or for use in form of a co-formulation. The formulations comprise additionally at least one buffering agent, such as e.g. a histidine buffer, a stabilizer or a mixture of two or more stabilizers (e.g. a saccharide, such as e.g. α,α-trehalose dihydrate or sucrose, and optionally methionine as a second stabilizer), a nonionic surfactant and an effective amount of at least one hyaluronidase enzyme. Methods for preparing such formulations and their uses thereof are also provided.

An enzymatic method is provided for treating ophthalmic disorders of the mammalian eye. Prevention of neovascularization and the increased rate of clearance from the vitreous of materials toxic to retina is accomplished by administering an amount of hyaluronidase effective to liquefy the vitreous humor of the treated eye without causing toxic damage to the eye. Liquefaction of the vitreous humor increases the rate of liquid exchange from the vitreal chamber. This increase in exchange removes those materials and conditions whose presence causes ophthalmological and retinal damage.

The invention discloses a construction method of recombinant bacillus subtilis capable of generating hyaluronic acid with specific molecular weight, belonging to the field of the bioengineering technology. According to the method, the production of hyaluronic acid is realized through integration of hyaluronic synthase (hasA) with streptococcus zooepidemicus source to bacillus subtilis; meanwhile, overexpression is realized on key genes of the synthetic route of HA, so that the high yield of bacillus subtilis is realized; on the basis, the hyaluronidase with the leech source is integrated to the genome of the bacillus subtilis, then mutant library construction is realized on ribosome bind sites (RBS) from the genetic expression translational level, and thus a series of mutants with different expression levels of hyaluronidases are obtained through high throughput screening; the yield of the hyaluronic acid achieves 19.38g / L, the molecular weight ranges from 103-106 Dalton, certain basis is laid for efficiently preparing micromolecule hyaluronic acids, and the construction method is suitable for industrial production and application.

The present invention provides compositions that contain botulinum toxin and a hyaluronidase, and that lack human or recombinant serum albumin. The present invention also provides methods of administering the pharmaceutical composition to a subject in need thereof.

The invention relates to a hyaluronic acid-modified amphipathic chitosan derivative carrier with tumor microenvironment specificity drug release effect. The hyaluronic acid-modified amphipathic chitosan derivative carrier is characterized in that firstly, a hydrophilic group is introduced into a chitosan skeleton; then, a hydrophobic group is introduced into a specifically degradable link arm containing disulfide bonds, so as to realize the amphipathic function; the amphipathic derivative is assembled into nanomicelle by self in a waterborne medium, and is further modified by a charge adsorbing principle to target the molecular hyaluronic acid; the nanomicelle can effectively load an anti-tumor drug, and the hyaluronic acid is targeted to the tumor microstructure and then is degraded by hyaluronic acid enzyme in focus cells, so that the drug can be quickly released from the nanomicelle to act on the focal part, thereby obviously improving the concentration, therapy effect and biological utilization degree of free drug on the focal part. The hyaluronic acid-modified amphipathic chitosan derivative carrier has the advantages that the carrier which carries pharmaceutical activity or pharmacological activity molecules can be applied to internal injection of blood vessels or muscles or oral administration, so as to obviously improve the anti-tumor activity of drug; the preparation method is simple, the technology is matured, and the preparation method is suitable for large-scale production.

A highly specific and easily purified form of hyaluronidase is described for use in ophthalmic treatments. The enzyme, from Streptomyces hyalurolyticus is specific for hyaluronidase and carries out an elimination reaction that results in the production of double bonds at the nonreducing end of hyaluronic acid. Hyaluronidase from Streptomyces hyalurolyticus has a higher activity than comparable enzymes from other species. The enzyme is now capable of being purified in what is essentially a protease-free form making it applicable to medical treatments. The use of this source of hyaluronidase in ophthalmic treatments is now made possible by its high activity, specificity for hyaluronidase and purity.

The invention relates to a novel bioconjugation protocol for peptide suitable for in vivo applications. Bioconjugation of the peptide to HA derivative increases its half life in circulation contributing for a high efficacy. More over, conjugate of HA derivative and peptide which is treated with hyaluronidase shows increased bioactivity. And also, in contrast to PEGylation, HA derivative can be conjugated with many numbers of peptide molecules per single HA derivative chain, which enables multiple action of peptide drugs.

The invention discloses a method for preparing ultra-low molecular weight hyaluronic acid oligosaccharides and a salt thereof through combination of solid-liquid biphasic enzymolysis and ultrafiltration. The method comprises the following steps: degrading hyaluronic acid and a salt thereof by utilizing hyaluronidase produced by bacilli; preparing high-concentration hyaluronic acid enzymatic hydrolysate by adopting the method of combining a solid-liquid biphasic enzymolysis system and an ultrafiltration system, and then performing inactivating, activated carbon adsorption and impurity removal,filtering and spray-drying to obtain the ultra-low molecular weight hyaluronic acid oligosaccharides and the salt thereof with the molecular weight of less than or equal to 3 kDa. The product preparedby the method is high in stability, ultra-low in molecular weight, good in inflammation resistance and percutaneous absorptivity, high in purity, strong in oxidation resistance, does not have cytotoxicity, has the advantages of repairing skin cell damage and the like, and can be widely applied to the fields of cosmetics, food and medicines. According to the method, the process flow is easy to operate; conditions are mild; various alcohols are not used; the energy consumption is relatively low; the method does not have damage to a product structure, does not have environmental pollution, and is suitable for large-scale industrial production.

Ophthalmic conditions such as presbyopia, myopia, and astigmatism can be corrected by the use of a molding contact lens in combination with a pharmaceutical composition suitable for delivery to the eye. The molding contact lenses are preferably commercially available and are not specifically designed for orthokeratology. The agents in the pharmaceutical compositions such as hyaluronase allow the cornea of the eye to be molded in order to correct the refractive error of the eye. The contact lenses and the pharmaceutical composition induce a change in the radius of curvature of the anterior surface of the cornea, thereby correcting the refractive error of the eye. One advantage of the inventive technique is that the patient with his or her own individual visual needs guides the treatment until the patient near and far visual needs are met. The present invention also provides for kits, which contain molding contact lenses, pharmaceutical composition suitable for delivery to the eye, and instructions, useful in the inventive system.

The invention belongs to the fields of enzymology and pharmaceutical chemistry, and relates to the low molecular hyaluronate, preparation method and purpose thereof. Concretely, the preparation method comprises a degradation step of hyaluronic acid or salt thereof whose molecular weight is greater than 1000 kDa by hyaluronidase prepared by Bacillus spp whose preservation number is CGMCC No. 5744 or SEQ ID No:2 coded hyaluronidase. The preparation of low molecular hyaluronic acid or salts thereof by using hyaluronidase produced by Bacillus spp of the present invention has the advantages of simple operation, mild condition, non-destroy of the product structure and low cost. The product is suitable for large scale industrialized production. The low molecular hyaluronate prepared by the invention has the advantages of good transdermal absorbency, good purity, non-cytotoxicity, good antioxidation, etc., and can be used in the fields of cosmetic, foodstuff and medicine.

The invention belongs to the field of cell biology and relates to a method for inducing differentiation from human umbilical cord mesenchymai stem cells (hucMSCs) into neural cells. The method comprises that HUCMSCs and Schwann cells are putted in Transwell with apertures of 0.4 microns to be co-cultured separately; a Schwann cell culture medium is utilized as a cell culture medium and half or all of the cell culture medium is replaced every three days; and then neural cells can be obtained after two weeks of culturing. Through a separate co-culturing method utilized by the invention, an umbilical cord can be digested by a mixture of composite collagenase NB4 and hyaluronidase and thus a large amount of HUCMSCs can be separated. High purity HUCMSCs can be obtained in third generation passage cells. In the invention, HUCMSCs are induced and differentiate into neural cells, wherein a cell differentiation rate is over 70%. Expressing rate ranges of specific markers, such as NF-200, nestin, Betar-III-tubulin, etc., of neural cells are from 70 to 80%.