Galderma Holding Sa

Galderma S.a.

Galderma Holdings Sa

Åke Öhrlund

Johan Olsson

Morgan Karlsson

Kristoffer Bergman

Anne Helander Kenne

Henrik Karlsson

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.

Process for efficient cross-linking of hyaluronic acid

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.

Injectable gel product

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.

Method for manufacturing a shaped cross-linked hyaluronic acid product

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&#x2033; as a function of strain (&#x3b3;) in an amplitude sweep, determining the crossover point as the point at which G&#x2032; and G&#x2033; have the same value, determining the strain &#x3b3;at the crossover point, and determining the flexibility of the injectable gel as &#x3b3;or proportional to &#x3b3;. 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.

Flexibility measurements of injectable gels

A method for manufacturing a shaped cross-linked hyaluronic acid product, the method 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.

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Uppsala, Sweden

Åke Öhrlund