Mobay Corporation

Miles Inc.

Nathan D Greene

Karen K Brown

Sharon A Bryant

Sandy L Trump

Ivo Van De Rijn

Linda L Ruiz

Terry H Wollen

Richard H Schultz

Curtis D Wilson

John O Mozier

The present disclosure is concerned with the production of high molecular weight hyaluronic acid suitable for medicinal administration to mammals without provoking an immune response from microbiological fermentation. The cultures may be prepared from specially developed strains of hyaluronic acid generating bacteria obtained by passaging in serologically negative host animal blood. The cultures are kept in log phase growth for an extended period by appropriate temperature, pH and glucose content adjustments. If the cultured strain is not hyaluronidase negative the hyaluronidase activity is inhibited. The hyaluronic acid is precipitated from the culture by the sequential addition of an anionic surfactant and then a cationic surfactant and extended from the precipitate with a high molarity aqueous calcium ion solution. The isolated aqueous hyaluronic acid solution may then be purified by passage through a nitrocellulose filter. Its pyrogenicity may be alleviated by treatment with a strong acid washed activated carbon.

Method for the microbiological production of non-antigenic hyaluronic

The present disclosure is concerned with procedures for adjusting the average molecular weight, the molecular weight distribution and the viscosity in solution of hyaluronic acid and its salts (HA), particularly its sodium and potassium salts. The average molecular weight can be increased and the molecular weight distribution can be narrowed by precipitating this material into a bath of a non-solvent containing a continuously moving device to which it can adhere as it precipitates. The solution viscosity of this or any high molecular weight, high viscosity HA can be reduced without substantially effecting its molecular weight by either a moderate temperature heat treatment or passage through a fine (one micron or less) pore filter as a one weight percent or stronger aqueous solution. The disclosure is also concerned with the high molecular weight low solution viscosity HA so obtained.

Low viscosity high molecular weight filter sterilizable hyaluronic acid

The present disclosure is concerned with the discovery that hyaluronic acid, an agent well known to reduce the sequelae of trauma in mammalian joint tissue when applied directly to the traumatized tissue, will be carried to such traumatized tissue by the mammal's natural processes if applied at a site remote from the traumatized tissue. Thus, hyaluronic acid, in any therapeutically acceptable form, can be administered by the typical remote routes including intravenous, intramuscular, subcutaneous and topical. This makes the utilization of hyaluronic acid much more convenient and attractive. For instance the treatment of arthritis in horse or human joints with hyaluronic acid no longer requires more difficult intra articular injections.

Remote administration of hyaluronic acid to mammals

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Leawood, KS, United States of America

Nathan D Greene