Use of hyaluronic acid or its derivatives to enhance delivery of antineoplastic agents

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.

1 - 274 . (canceled)  
   
   
       275 . A method of prophylactically or therapeutically treating a human suffering from a form of cancer, said method comprising: 
 (1) directly injecting into a tumor in the human a non-toxic dosage amount of pharmaceutical composition comprising: 
 (i) an anti-cancer drug and/or drug suitable for use to treat cancer, and  
 (ii) a form of hyaluronic acid selected from the group consisting of hyaluronic acid, pharmaceutically acceptable salts thereof, and combinations thereof, wherein the form of hyaluronic acid has a molecular weight less than 750,000 daltons and is in sterile water, and  
   (2) administering systemically to the human, a non-toxic dosage amount of a pharmaceutical composition comprising: 
 (i) a form of hyaluronic acid selected from the group consisting of hyaluronic acid, phamaceutically acceptable salts thereof, and combinations thereof.  
 (ii) a drug selected from the group consisting of: 
 (a) a non-steroidal anti-inflammatory drug (NSAID),  
 (b) a chemotherapeutic agent, and  
 (c) combinations thereof, and optional  
 
 (iii) an anti-oxidant.  
   
   
   
       276 . The method of  claim 276 , wherien steps (1) and (2) are administered to the human one to four times monthly or more.  
   
   
       277 . The method of  claim 275 , wherein the form of cancer is breast cancer and steps (1) and (2) are administered to the human one to three times monthly or more.  
   
   
       278 . The method of  claim 275 , wherein administering systemically is by intravenous administration.  
   
   
       279 . The method of  claim 275 , further comprising treating the human by hyperthermia.  
   
   
       280 . A method of prophylactically or therapeutically treating a human suffering from a form of cancer, said method comprising: 
 (1) administering systemically to the human a first dosage amount of a pharmaceutical composition comprising a drug suitable for treating cancer, alone or in combination with a form of hyaluronic acid, selected from the group consisting of hyaturonic acid, pharmaceutically acceptable salts thereof, and combinations thereof, having a molecular weight of less than 750,000 daltons; and    (2) administering systemically to the human a second dosage amount of a phamaceutical composition comprising: 
 (i) a form of hyaluronic acid selected from the group consisting of hyaluronic acid, pharmaceutically acceptable salts thereof, and combinations thereof, having a molecular weight less than 750,000 daltons;  
 (ii) a drug selected from the group consisting of; 
 (a) a non-steroidal anti-inflammatory drug (NSAID),  
 (b) a chemotherapeutic agent, and  
 (c) combinations thereof, and, optionally  
 
 (iii) an anti-oxidant,  
   wherein the first and second dosage amounts are not the same and can be administered to the human sequentially or concomitantly.    
   
   
       281 . The method of treatment of  claim 280 , wherein steps (1) and (2) are repeated at least two times or more.  
   
   
       282 . A method of prophylactically or therapeutically treating a human suffering from a metastatic form of cancer, said method of treatment comprising: 
 (1) administering systemically to the human a first dosage amount of a pharmaceutical composition comprising a drug suitable for treating cancer, alone or in combination with a form of hyaluronic acid selected from the group consisting of hyaluronic acid, pharmaceutically acceptable salts thereof, and combinations thereof, having a molecular weight less than 750,000 daltons, and    (2) administering systemically to the human a second dosage amount of pharmaceutical composition comprising: 
 (i) a form of hyaluronic acid selected from the group consisting of hyaluronic acid, pharmaceutically acceptable salts thereof, and combination thereof, having a molecular weight less than 750,000 daltons,  
 (ii) a drug selected from the group consisting of: 
 (a) a non-steroidal anti-inflammatory drug (NSAID),  
 (b) a chemotherapeutic agent, and  
 (c) combinations thereof, and optionally,  
 
 (iii) an anti-oxidant,  
   wherein said first and second dosage amounts are not the same, can be administered to the human sequntially or concomitantly, and can be administered to the human at regular intervals during a period of treatment.    
   
   
       283 . The method of treatment of  claim 282 , wherein steps (1) and (2) are administered to the human about 1-4 times monthly.  
   
   
       284 - 286 . (canceled)  
   
   
       287 . A method of prophylactically or therapeutically treating a human suffering from cancer, said method comprising: 
 (1) directly injecting into a tumor in the human a non-toxic dosage amount of a pharmaceutical composition comprising novantrone and sodium hyluronate in sterile water, said sodium hyaluronate having a molecular weight less than 750,000 daltons, and    (2) administering systemically to the human a non-toxic dosage amount of a pharmaceutical composition comprising 
 (i) sodium hyaluronate having a molecular weight less than 750,000 daltons,  
 (ii) a drug selected fro the group consisting of: 
 (a) diclofenac sodium,  
 (b) novantrone, and  
 (c) combinations thereof, and, optionally,  
 
 (iii) Vitamin C.  
   
   
   
       288 . (canceled)  
   
   
       289 . The method of  claim 275 , wherein the systemically administered form of hyaluronic acid is sodium hyaluronate having a molecular weight less than about 750,000 daltons.  
   
   
       290 . The method of  claim 275 , wherein steps (1) and (2) are repeated at least two times or more to prevent or reduce metastases.  
   
   
       291 . The method of  claim 280 , wherein the first dosage amount further comprises hyaluronic acid, pharmaceutically acceptable salts thereof, or combinations thereof, having a molecular weight less than 750,000 daltons.  
   
   
       292 . The method of  claim 280 , wherein the second dosage amount further comprises an anti-oxidant.  
   
   
       293 . A method of prophylactically or therapeutically treating a human suffering from a metastatic form of cancer, said method of treatment comprising: 
 a. directly injecting into a tumor in the human a non-toxic dosage amount of a pharmaceutical composition comprising: 
 i. an anti-cancer drug and/or suitable for use to treat cancer, and  
 ii. a form of hyaluronic acid selected from the group consisting of hyaluronic acid, pharmaceutically acceptable salts thereof, and combinations thereof, wherein the for of hyaluronic acid has a molecular weight less than 750,000 daltons and is in sterile water, and  
   b. administrating systemically to the human, a non-toxic dosage amount of a pharmaceutical composition comprising: 
 i. a form of hyaluronic acid selected from the group consisting of hyaluronic acid, pharmaceutically acceptable salts thereof, and combinations thereof.  
 ii. A drug selected from the group consisting of: 
 1. a non-steroidal anti-inflammatoy drug (NSAID),  
 2. a chemotherapeutic agent, and  
 3. combinations thereof, and optionally  
 
 iii. an anti-oxidants,  
   
   
   
       294 . The method of  claim 293 , wherein steps (1) and (2) are administered to the human one to four times monthly, or more.  
   
   
       295 . The method of  claim 282 , wherein the first dosage amount further comprises hyaluronic acid, pharmaceutically acceptable salts thereof, or combinations thereof, having a molecular weight less than 750,000 daltons.  
   
   
       296 . The method of  claim 282 , wherein the second dosage amount further comprises an anti-oxidant.