Abstract: 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.

Abstract: 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.