Abstract: A process for manufacturing a cross-linked hyaluronic acid (HA) gel product is comprising the steps of: (a) preparing an aqueous mixture of HA and a cross-linking agent selected from multiepoxides and diepoxides; wherein the HA is dissolved in an aqueous solution containing 1-10% (w/w) inorganic hydroxide; and wherein the dissolved HA constitutes more than 10% (w/w) of the final mixture; and (b) subjecting the aqueous mixture to cross-linking conditions to allow the dissolved HA to react with the cross-linking agent so as to obtain a cross-linked HA gel product.

Abstract: A method of producing an injectable gel product is provided, comprising (a) cross-linking a first glycosaminoglycan (GAG) with a first crosslinking agent to produce a gel, wherein the charging ratio of crosslinking agent to disaccharide unit is below 0.15; (b) preparing particles of the gel; (c) mixing the glycosaminoglycan (GAG) gel particles with a second GAG to provide a mixture; (d) cross-linking the mixture with a second crosslinking agent to obtain cross-linking between the GAGs of the second, outer phase, thereby providing a gel having a first, inner phase of the cross-linked GAG gel particles, embedded in a gel of the second GAG outer phase; and (e) preparing injectable particles, each such particle containing a plurality of the cross-linked GAG gel particles of the first, inner phase. An injectable gel product, an aqueous composition, and a pre-filled syringe as also provided.

Abstract: A process for manufacturing a cross-linked hyaluronic acid (HA) gel product is comprising the steps of: (a) preparing an aqueous mixture of HA and a cross-linking agent selected from multiepoxides and diepoxides; wherein the HA is dissolved in an aqueous solution containing 1-10% (w/w) inorganic hydroxide; and wherein the dissolved HA constitutes more than 10% (w/w) of the final mixture; and (b) subjecting the aqueous mixture to cross-linking conditions to allow the dissolved HA to react with the cross-linking agent so as to obtain a cross-linked HA gel product.

Abstract: Described are high molecular weight glycosaminoglycan (GAG) hydrogel compositions comprising GAGs covalently crosslinked with a carbohydrate crosslinker, and methods of making the high molecular weight GAG hydrogel compositions. Further described are methods of using the high molecular weight glycosaminoglycan (GAG) hydrogel compositions for reparative or plastic surgery, esthetic dermatology, facial contouring, body contouring, and gingival augmentation.

Abstract: Described are high molecular weight glycosaminoglycan (GAG) hydrogel compositions comprising GAGs covalently crosslinked with a carbohydrate crosslinker, and methods of making the high molecular weight GAG hydrogel compositions. Further described are methods of using the high molecular weight glycosaminoglycan (GAG) hydrogel compositions for reparative or plastic surgery, esthetic dermatology, facial contouring, body contouring, and gingival augmentation.

Abstract: A method for manufacturing a shaped cross-linked hyaluronic acid product including the step of subjecting a non-cross-linked precipitated hyaluronic acid substrate in a desired shape to a single cross-linking reaction in a liquid medium having a pH of 11.5 or higher and including one or more polyfunctional cross-linking agent(s) and an amount of one or more organic solvent(s) giving precipitating conditions for hyaluronic acid, under suitable conditions to obtain a precipitated, shaped cross-linked hyaluronic acid product having a degree of modification of 1-40 cross-linking agent units per 1000 disaccharide units.

Abstract: A process for evaluating rheological characteristics of an injectable gel including measuring the flexibility, wherein the flexibility is evaluated by measuring the strain at the crossover point of the amplitude sweep. The process may include subjecting an injectable gel to oscillating mechanical stresses to determine G? and G? as a function of strain (?) in an amplitude sweep, determining the crossover point as the point at which G? and G? have the same value, determining the strain ?cross at the crossover point, and determining the flexibility of the injectable gel as ?cross or proportional to ?cross. Further, a method of comparison of dermal fillers by measuring their flexibility and a method of evaluation of dermal filler behavior in human skin by measuring the flexibility.

Abstract: A method of producing an injectable gel product is provided, comprising (a) cross-linking a first glycosaminoglycan (GAG) with a first crosslinking agent to produce a gel, wherein the charging ratio of crosslinking agent to disaccharide unit is below 0.15; (b) preparing particles of the gel; (c) mixing the glycosaminoglycan (GAG) gel particles with a second GAG to provide a mixture; (d) cross-linking the mixture with a second crosslinking agent to obtain cross-linking between the GAGs of the second, outer phase, thereby providing a gel having a first, inner phase of the cross-linked GAG gel particles, embedded in a gel of the second GAG outer phase; and (e) preparing injectable particles, each such particle containing a plurality of the cross-linked GAG gel particles of the first, inner phase. An injectable gel product, an aqueous composition, and a pre-filled syringe as also provided.

Abstract: A method of producing an injectable gel product is provided, comprising (a) cross-linking a first glycosaminoglycan (GAG) with a first crosslinking agent to produce a gel, wherein the charging ratio of crosslinking agent to disaccharide unit is below 0.15; (b) preparing particles of the gel; (c) mixing the glycosaminoglycan (GAG) gel particles with a second GAG to provide a mixture; (d) cross-linking the mixture with a second crosslinking agent to obtain cross-linking between the GAGs of the second, outer phase, thereby providing a gel having a first, inner phase of the cross-linked GAG gel particles, embedded in a gel of the second GAG outer phase; and (e) preparing injectable particles, each such particle containing a plurality of the cross-linked GAG gel particles of the first, inner phase. An injectable gel product, an aqueous composition, and a pre-filled syringe as also provided.

Abstract: The present disclosure relates to compositions comprising hydrogels and solid particles and their use. More specifically, the proposed technique relates to methods for manufacturing of a composition comprising solid particles encapsulated within crosslinked polysaccharide molecules forming hydrogel particles, the method comprising mixing water-soluble polysaccharide molecules comprising one or more carboxyl groups, water insoluble solid particles, a di- or multinucleophilic functional crosslinker, and a coupling agent, in a water suspension at pH between 5 and 9, to form a composition comprising a hydrogel of crosslinked polysaccharide molecules encapsulating the solid particles. The disclosure comprises the composition, methods for producing the composition and use of the composition as a dermal filler.

Abstract: A method for manufacturing a shaped cross-linked hyaluronic acid product including the step of subjecting a non-cross-linked precipitated hyaluronic acid substrate in a desired shape to a single cross-linking reaction in a liquid medium having a pH of 11.5 or higher and including one or more polyfunctional cross-linking agent(s) and an amount of one or more organic solvent(s) giving precipitating conditions for hyaluronic acid, under suitable conditions to obtain a precipitated, shaped cross-linked hyaluronic acid product having a degree of modification of 1-40 cross-linking agent units per 1000 disaccharide units.

Abstract: Described are high molecular weight glycosaminoglycan (GAG) hydrogel compositions comprising GAGs covalently crosslinked with a carbohydrate crosslinker, and methods of making the high molecular weight GAG hydrogel compositions. Further described are methods of using the high molecular weight glycosaminoglycan (GAG) hydrogel compositions for reparative or plastic surgery, esthetic dermatology, facial contouring, body contouring, and gingival augmentation.

Abstract: A process for manufacturing a cross-linked hyaluronic acid (HA) gel product is comprising the steps of: (a) preparing an aqueous mixture of HA and a cross-linking agent selected from multiepoxides and diepoxides; wherein the HA is dissolved in an aqueous solution containing 1-10% (w/w) inorganic hydroxide; and wherein the dissolved HA constitutes more than 10% (w/w) of the final mixture; and (b) subjecting the aqueous mixture to cross-linking conditions to allow the dissolved HA to react with the cross-linking agent so as to obtain a cross-linked HA gel product.

Abstract: A process for manufacturing a cross-linked hyaluronic acid (HA) gel product is comprising the steps of: (a) preparing an aqueous mixture of HA and a cross-linking agent selected from multiepoxides and diepoxides; wherein the HA is dissolved in an aqueous solution containing 1-10% (w/w) inorganic hydroxide; and wherein the dissolved HA constitutes more than 10% (w/w) of the final mixture; and (b) subjecting the aqueous mixture to cross-linking conditions to allow the dissolved HA to react with the cross-linking agent so as to obtain a cross-linked HA gel product.

Abstract: A method for manufacturing a shaped cross-linked hyaluronic acid product including the step of subjecting a non-cross-linked precipitated hyaluronic acid substrate in a desired shape to a single cross-linking reaction in a liquid medium having a pH of 11.5 or higher and including one or more polyfunctional cross-linking agent(s) and an amount of one or more organic solvent(s) giving precipitating conditions for hyaluronic acid, under suitable conditions to obtain a precipitated, shaped cross-linked hyaluronic acid product having a degree of modification of 1-40 cross-linking agent units per 1000 disaccharide units.

Abstract: A method of producing an injectable gel product is provided, comprising (a) cross-linking a first glycosaminoglycan (GAG) with a first crosslinking agent to produce a gel, wherein the charging ratio of crosslinking agent to disaccharide unit is below 0.15; (b) preparing particles of the gel; (c) mixing the glycosaminoglycan (GAG) gel particles with a second GAG to provide a mixture; (d) cross-linking the mixture with a second crosslinking agent to obtain cross-linking between the GAGs of the second, outer phase, thereby providing a gel having a first, inner phase of the cross-linked GAG gel particles, embedded in a gel of the second GAG outer phase; and (e) preparing injectable particles, each such particle containing a plurality of the cross-linked GAG gel particles of the first, inner phase. An injectable gel product, an aqueous composition, and a pre-filled syringe as also provided.

Abstract: A method for manufacturing a shaped cross-linked hyaluronic acid product including the step of subjecting a non-cross-linked precipitated hyaluronic acid substrate in a desired shape to a single cross-linking reaction in a liquid medium having a pH of 11.5 or higher and including one or more polyfunctional cross-linking agent(s) and an amount of one or more organic solvent(s) giving precipitating conditions for hyaluronic acid, under suitable conditions to obtain a precipitated, shaped cross-linked hyaluronic acid product having a degree of modification of 1-40 cross-linking agent units per 1000 disaccharide units.

Abstract: A process for evaluating rheological characteristics of an injectable gel including measuring the flexibility, wherein the flexibility is evaluated by measuring the strain at the crossover point of the amplitude sweep. The process may include subjecting an injectable gel to oscillating mechanical stresses to determine G? and G? as a function of strain (?) in an amplitude sweep, determining the crossover point as the point at which G? and G? have the same value, determining the strain ?cross at the crossover point, and determining the flexibility of the injectable gel as ?cross or proportional to ?cross. Further, a method of comparison of dermal fillers by measuring their flexibility and a method of evaluation of dermal filler behavior in human skin by measuring the flexibility.

Abstract: Efficient cross-linking of hyaluronic acid (HA) is provided by a manufacturing process. In the process, HA is activated by an initial cross-linking in an aqueous solution. Unreacted cross-linking agent is removed from the activated HA. Cross-linking of the activated HA is finalized, without addition of any additional cross-linking agent, in a suspension of a liquid precipitating medium and the activated HA in precipitated form. The resulting cross-linked HA products exhibit high effective cross-linker ratio and other favorable properties, making the products useful as implants and in medical and cosmetic surgery.

Abstract: A method for manufacturing a shaped cross-linked hyaluronic acid product including the step of subjecting a non-cross-linked precipitated hyaluronic acid substrate in a desired shape to a single cross-linking reaction in a liquid medium having a pH of 11.5 or higher and including one or more polyfunctional cross-linking agent(s) and an amount of one or more organic solvent(s) giving precipitating conditions for hyaluronic acid, under suitable conditions to obtain a precipitated, shaped cross-linked hyaluronic acid product having a degree of modification of 1-40 cross-linking agent units per 1000 disaccharide units.