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Details for Patent: 6,194,392

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Details for Patent: 6,194,392

Title: Treatment of conditions and disease
Abstract:A combination for administration to a mammal which combination employs a therapeutically effective amount of a medicinal and/or therapeutic agent to treat a disease or condition and an amount of hyaluronic acid and/or salts thereof and/or homologues, analogues, derivatives, complexes, esters, fragments and subunits of hyaluronic acid sufficient to facilitate the agent's penetration through the tissue (including scar tissue) at the site to be treated, through the cell membranes into the individual cells to be treated.
Inventor(s): Falk; Rudolf Edgar (Toronto, CA), Asculai; Samuel S. (Toronto, CA)
Assignee: Hyal Pharmaceutical Corporation (Mississauga, CA)
Filing Date:Aug 07, 1995
Application Number:08/460,978
Claims:1. A method of treating a patient suffering from swelling associated with brain tumours involving tissue selected from the group consisting of underperfused tissue and pathological tissue comprising administering to the patient a therapeutically effective dosage amount of an agent selected from the group consisting of a medicine and a therapeutic agent and combinations thereof to treat the swelling associated with brain tumours and a sufficient amount of a form of hyaluronic acid selected from the group consisting of hyaluronic acid, its non-toxic salts and combinations thereof sufficient to facilitate the penetration of the agent through the tissue at a site to be treated through the cell membranes into the individual cells to be treated wherein the molecular weight of the form of hyaluronic acid is in the range of 150,000 to 750,000 daltons, and said amount of the form of hyaluronic acid is sufficient to provide a dosage greater than 10 mg and less than 3000 mg.

2. A dosage amount of a pharmaceutical composition for treating a patient suffering from swelling associated with brain tumors and in respect of which swelling has occurred involving tissue selected from the group consisting of underperfused tissue and pathological tissue, said dosage amount comprising a therapeutically effective dosage amount of dimethyl sulfoxide (DMSO) and a sufficient amount of a form of hyaluronic acid selected from the group consisting of hyaluronic acid, its non-toxic salts and combinations thereof to facilitate the DMSO at a site to be treated by the DMSO passing through the tissue through the cell membranes into the individual cells to be treated wherein the molecular weight of the form of hyaluronic acid is in the range of 150,000 to 750,000 daltons, and said amount of the form of hyaluronic acid is sufficient to provide a dosage greater than 10 mg and less than 1000 mg.

3. The dosage amount of claim 2 wherein the amount of the form of hyaluronic acid is greater than 250 mg and less than 550 mg and the amount of DMSO is less than 100 g.

4. A dosage amount of a pharmaceutical composition for treatment of bone pain, muscle pain and inflammation associated with neoplastic treatment involving tissue selected from the group consisting of underperfused tissue and pathological tissue, said dosage amount comprising a therapeutically effective dosage amount of ascorbic acid and a sufficient amount of a form of hyaluronic acid selected from the group consisting of hyaluronic acid, its non-toxic salts and combinations thereof to facilitate the ascorbic acid at a site to be treated by the ascorbic acid passing through the tissue through the cell membranes into the individual cells to be treated wherein the molecular weight of the form of hyaluronic acid is in the range of 150,000 to 750,000 daltons, and said amount of the form of hyaluronic acid is sufficient to provide a dosage greater than 10 mg and less than 1000 mg.

5. The dosage amount of claim 2, 3, or 4 wherein the form of hyaluronic acid is sodium hyaluronate.

6. A method of treating bone pain, muscle pain and inflammation associated with neoplastic treatment involving tissue selected from the group consisting of underperfused tissue and pathological tissue, the method comprising the administration of a therapeutically effective amount of ascorbic acid and a sufficient amount of a form of hyaluronic acid selected from the group consisting of hyaluronic acid, its non-toxic salts and combinations thereof to facilitate the ascorbic acid at a site to be treated by the ascorbic acid passing through the tissue through the cell membranes into the individual cells to be treated wherein the molecular weight of the form of hyaluronic acid is in the range of 150,000 to 750,000 daltons, and said amount of the form of hyaluronic acid is sufficient to provide a dosage greater than 10 mg and less than 3000 mg.

7. The method of claim 6 or 1 wherein the form of hyaluronic acid is sodium hyaluronate.

8. A method of enhancing oxygenation of tissue by perfusion fluid bathing the tissue involving tissue selected from the group consisting of underperfused tissue and pathological tissue, the method comprising the administration of perfusate fluid agent and a sufficient dosage amount of a form of hyaluronic acid selected from the group consisting of hyaluronic acid, its non-toxic salts and combinations thereof to facilitate the agent at a site to be treated by the agents passing through the tissue through the cell membranes into the individual cells to be treated wherein the molecular weight of the form of hyaluronic acid is in the range of 150,000 to 750,000 daltons, and said amount of the form of hyaluronic acid is sufficient to provide a dosage greater than 10 mg and less than 1000 mg.

9. The method of claim 8 wherein the form of hyaluronic acid is sodium hyaluronate and the dosage amount is greater than 200 mg.

10. A method of increasing macrophage activity in humans suffering from a condition or disease involving underperfused or pathological tissue, comprising administering a therapeutically effective amount of at least one agent selected from the group consisting of a free radical scavenger, superoxide dismutase, ascorbic acid, an anti-cancer drug, a non-steroidal anti-inflammatory drug (NSAID) and a detoxifying drug, and an effective dosage amount of a form of hyaluronic acid selected from the group consisting of hyaluronic acid and non-toxic salts thereof, wherein said amount of the form of hyaluronic acid is between 10 mg and 3000 mg and is sufficient to facilitate penetration of the agent and the form of hyaluronic acid to the site involving underperfused or pathological tissue and for the drug to increase macrophage activity and wherein the form of hyaluronic acid has a molecular weight less than 750,000 daltons but greater than 150,000 daltons.

11. A method of claim 10 wherein the agent is a non-steroidal anti-inflammatory drug (NSAID) and the amount of the form of hyaluronic acid is between 10 mg and 1000 mg.

12. The method of claim 11 wherein the form of hyaluronic acid is sodium hyaluronate and is in an amount of at least 200 mg.

13. The method claim 11 or 12 wherein the non-steroidal anti-inflammatory drug (NSAID) is selected from the group consisting of indomethacin, naproxen, ketorolac tromethamine salt, diclofenac, piroxicam and ibuprofen.

14. A pharmaceutical composition for increasing activity of macrophages in humans suffering from a disease or condition involving pathological or underperfused tissue comprising (a) an effective dosage amount of a non-steroidal anti-inflammatory drug (NSAID) and (b) an amount of a form of hyaluronic acid selected from the group consisting of hyaluronic acid and non-toxic salts thereof, wherein said amount of the form of hyaluronic acid is between 10 mg and 3000 mg per said dosage amount, and is sufficient to facilitate penetration of the NSAID to the site involving underperfused or pathological tissue, and to increase macrophage activity, and wherein the form of hyaluronic acid has a molecular weight less than 750,000 daltons and greater than 150,000 daltons.

15. The composition of claim 14 wherein the composition provides at least 200 mg of sodium hyaluronate per said dosage amount.

16. The composition of claim 14 or 15 wherein the non-steroidal anti-inflammatory drug (NSAID) is selected from the group consisting of diclofenac, piroxicam, ibuprofen, indomethacin, naproxen, and ketorolac tromethamine salt.
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