New medicaments for topical use

Claim 2

A medicament for topical use comprising: a) a pharmaceutically active substance or a mixture of pharmaceutically active substances suitable for topical administration; and b) hyaluronic acid or a molecular weight fraction of the same, or a salt of hyaluronic acid or said fraction of hyaluronic acid with an alkali or alkaline earth metal, aluminum or ammonium or a salt of hyaluronic acid or said fraction of hyaluronic acid with said active substance(s), or mixtures thereof.

Claim 3

A medicament for topical use comprising a salt of hyaluronic acid or a molecular weight fraction thereof with at least one pharmacologically active substance suitable for topical administration.

Claim 4

A medicament for topical use comprising a salt of hyaluronic acid or a molecular weight fraction thereof with at least one pharmacologically active substance suitable for topical administration.

Claim 5

A medicament according to claim 2, wherein said hyaluronic acid is further salified with an alkali or alkaline earth metal, aluminum or ammonium.

Claim 6

A medicament according to any one of claims 1-3, wherein the active substance has ophthalmological or dermatological activity.

Claim 7

A medicament according to any one of claims 1-4, comprising at least one antibiotic, anti-infective, antimicrobial, antiviral, cytostatic, antitumor, anti-inflammatory, wound healing, anesthetic, cholinergic promoter, cholinergic antagonist, adrenergic promotor or adrenergic antagonist agent.

Claim 8

6 . A medicament according to claim 5, containing at least one active substance selected from the group consisting of erythromycin, gentamycin, neomycin, streptomycin, dihydrostreptomycin, kanamycin, amikacyn, tobramycin, aureomycin, spectinomycin, erythromycin, oleandomycin, carbomycin, spiramycin, oxytetracycline, rolitetracycline, bacitracin, polymyxin B, gramicidin, colistin, chloramphenicol, lincomycin, amphotericin B, griseofulvin, nystatin, diethylcarbamazine, mebendazol, sulfacetamide, sulfadiazine, sulfisoxazole, iodeoxyuridine, adenine arabinoside, tricarpine, metacholine, carbamylcholine, aceclidine, fisostigmine, neostigmine, demacarium, stropina, propanolol timolol, pindolol, bupranolol, atenolol, metoprolol, oxprenolol, practolol, butoxamine, sotalol, butadrine, labetalol, dexamethasone, triamcinolone, prednisolone, fluorometholone, medrison, fluorocil, methotrexate and podophyllin.

Claim 9

A medicament according to any one of claims 1-6, further containing as an anti-inflammatory agent prednisolone, dexamethasone, flumethasone, triamcinolone, acetonide, betamethasone, clobetasol or esters thereof, or containing as an anesthetic agent dibucaine, lidocaine or benzocaine.

Claim 10

A medicament according to any one of claims 1-7, in which the hyaluronic acid fraction used has a molecular weight of between about 90-80% and 0.23% of the molecular weight of integral hyaluronic acid having a molecular weight of 13 million.

Claim 11

A medicament according to any one of claims 1-8, in which the hyaluronic acid comprises a purified molecular weight fraction of hyaluronic acid being substantially free of hyaluronic acid having a molecular weight less than about 30,000.

Claim 12

A medicament according to claim 9, in which the molecular weight fraction of hyaluronic acid has an average molecular weight of about 50,000 to about 100,000, about 500,000 to about 730,000 or about 250,000 to about 350,000.

Claim 13

A medicament according to any one of claims 1-10, wherein said salt of hyaluronic acid is a partial acid salt of hyaluronic acid or a molecular weight fraction thereof with a pharmaceutically active substance of a basic character.

Claim 14

A medicament according to any one of claims 1-10, wherein said salt of hyaluronic acid is a stoichiometrically neutral salt of hyaluronic acid or a molecular weight fraction thereof with a pharmaceutically active substance of a basic character.

Claim 15

A medicament according to any one of claims 1-10, containing a mixture of a partial acid salt of hyaluronic acid or a molecular weight fraction thereof, and a stoichiometrically neutral salt of hyaluronic acid or a molecular weight fraction thereof.

Claim 16

A medicament for topical use according to any one of claims 1-13, including an additional pharmaceutically acceptable excipient suitable for topical use.

Claim 17

A therapeutic or prophylactic method for the treatment of ophthalmic conditions, dermatological conditions, diseases of the mucous of the oral and nasal cavities or of the outer ear, for the treatment of pathologies of the internal organs with active substances which may be absorbed intradermally or through the nasal or rectal mucous, said method comprises administering a medicament according to any one of claims 1-13.

Claim 18

A process for the preparation of a hyaluronic acid salt which comprises: a) combining an aqueous solution of a barium salt of hyaluronic acid with a sulfate of a pharmaceutically active substance; and b) separating the precipitated barium sulfate to obtain the hyaluronic acid salt in aqueous solution.

Claim 19

A process for the preparation of a hyaluronic acid salt which comprises: a) combining an aqueous solution of a barium salt of hyaluronic acid with a sulfate of a pharmaceutically active substance; and b) separating the precipitated barium sulfate to obtain the hyaluronic acid salt in aqueous solution.

Claim 20

A process according to claim 16, wherein said sulfate is added in an amount such that the number of sulfate equivalents is equal to the number of hyaluronic acid equivalents, thereby producing a stoichiometrically neutral hyaluronic acid salt.

Claim 21

A process according to claim 16, wherein sail sulfate is added in an amount such that the number of sulfate equivalents is less than the number oi hyaluronic acid equivalents, thereby producing partially salified hyaluronic acid salt.

Claim 22

A process according to claim 16, wherein said barium salt of hyaluronic acid is further combined with a sulfate of at least one member selected from the group consisting of an alkali or alkaline earth metal, aluminum or ammonium.

Claim 23

A process according to claim 19, wherein said sulfates are added in an amount such that the number of sulfate equivalents is equal to the number of hyaluronic acid equivalents.

Claim 24

A process according to claim 19, wherein said sulfates are added in an amount such that the number of sulfate equivalents is less than the number of hyaluronic acid equivalents.

Claim 25

A process according to any one of claims 23-28, wherein said active substance is at least one member selected from erythromycin, gentamycin, neomycin, streptomycin, dihydrostreptomycin, kanamycin, amikacyn, tobramycin, aureomycin, spectinomycin, erythromycin, oleandomycin, carbomycin, spiramycin, oxytetracycline, rolitetracycline, bacitracin, polymyxin B, gramicidin, colistin, chloramphenicol, lincomycin, amphotericin B, griseofulvin, nystatin, diethylcarbamazine, mebendazol, sulfacetamide, sulfadiazine, sulfisoxazole, iodeoxyuridine, adenine arabinoside, tricarpine, metacholine, carbamylcholine, aceclidine, fisostigmine, neostigmine, demacarium, stropina, propanolol timolol, pindolol, bupranolol, atenolol, metoprolol, oxprenolol, practolol, butoxamine, sotalol, butadrine, labetalol, dexamethasone, triamcinolone, prednisolone, fluorometholone and medrison.

Claim 26

A process according to any one of claims 16-22, wherein the hyaluronic acid is a molecular weight fraction having a molecular weight of between about 90-80% and 0.23% of the molecular weight of integral hyaluronic acid having a molecular weight of 13 million.

Claim 27

A process according to claim 23, wherein the hyaluronic acid fraction is substantially free of hyaluronic acid having a molecular weight less than about 30,000.

Claim 28

A process according to claim 24, wherein the molecular weight fraction has an average molecular weight of about 50,000 to about 100,000, about 500,000 to about 730,000 or about 250,000 to about 350,000.

Claim 29

The barium salt of a substantially pure non-inflammatory hyaluronic fraction having an average molecular weight of between 250,000 to 350,000, 50,000 to 100,000 or between 500,000 to 730,000 and being substantially free of hyaluronic acid having molecular weight less than 30,000.

Claim 30

The barium salt of a substantially pure non-inflammatory hyaluronic fraction having an average molecular weight of between 250,000 to 350,000, 50,000 to 100,000 or between 500,000 to 730,000 and being substantially free of hyaluronic acid having molecular weight less than 30,000.

Claim 31

A process for the preparation of a barium salt of hyaluronic acid or a molecular weight fraction thereof which comprises -a) treating a cetylpyridinium salt of hyaluronic acid or a molecular weight fraction thereof with an aqueous solution of barium chloride; and b) separating the aqueous solution and adding ethanol to thereby precipitate the barium salt of hyaluronic acid or of a molecular weight fraction thereof.

Claim 32

A process for the preparation of a barium salt of hyaluronic acid or a molecular weight fraction thereof which comprises -a) treating a cetylpyridinium salt of hyaluronic acid or a molecular weight fraction thereof with an aqueous solution of barium chloride; and b) separating the aqueous solution and adding ethanol to thereby precipitate the barium salt of hyaluronic acid or of a molecular weight fraction thereof.

Claim 33

A process according to claim 27, wherein the hyaluronic acid fraction is substantially free of hyaluronic acid having a molecular weight less than about 30,000.

Claim 34

A process according to claim 27, wherein said molecular weight fraction has an average molecular weight of about 50,000 to about 100,000, about 500,000 to about 730,000 or about 250,000 to about 350,000.