Materials for treating and preventing mucosa related disease

Abstract

Provided is a hyaluronic acid (HA) composition for use in treating or preventing mucosa related disorders or diseases including a mixture of HAs having different average molecular weights and different rheological, isolation, tissue scaffold and degradation properties. The resulting formulation demonstrates an optimal balance between adhesion, tissue scaffold and treating time on the treatment and prevention of mucosa related disorders or diseases including conjunctivitis, otitis, allergic rhinitis, gingivitis, oral ulcer, bronchitis, gastroesophageal reflux disease (GERD), esophagitis, gastritis, enteritis, peptic ulcer, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), urethritis, cystitis and vaginitis.

1 . A composition for use in treating or preventing a mucosa related disorder or disease comprising:
 a therapeutically effective amount of a hyaluronic acid mixture including a low average molecular weight hyaluronic acid (LMWHA) and a high average molecular weight hyaluronic acid (HMWHA), wherein the average molecular weight (Mw) of LMWHA is between 50 kilo Da and 1.5 million Da, and the average Mw of HMWHA is between 1.5 million Da and 5 million Da, but 1.5 million Da is excluded from both the average molecular weights of the LMWHA and of the HMWHA, wherein the average Mw of LMWHA is apart from the average Mw of HMWHA by a least 0.5 million Da, and a mixing ratio of the LMWHA to the HMWHA is in a range from 20:80 to 80:20 by weight; wherein the mucosa is the mucosa of an eye, the mucosa of an ear, the mucosa of a nose, the mucosa of a mouth, the mucosa of a respiratory tract, the mucosa of a gastrointestinal tract, the mucosa of a urinary tract and the mucosa of a genital tract.   
     
     
         2 . The composition of  claim 1 , wherein the average Mw of LMWHA is between 0.1 million Da and 1.5 million Da. 
     
     
         3 . The composition of  claim 2 , wherein the average Mw of LMWHA is between 0.1 million Da and 3.5 million Da. 
     
     
         4 . The composition of  claim 1 , wherein the average Mw of HMWHA is between 1.5 million Da and 3.5 million Da. 
     
     
         5 . The composition of  claim 4 , wherein the average Mw of HMWHA is between 1.5 million Da and 2.5 million Da. 
     
     
         6 . The composition of  claim 1 , wherein the mixing ratio of the LMWHA to HMWHA is 1:1 by weight. 
     
     
         7 . The composition of  claim 1 , wherein the therapeutically effective amount is at a range from 0.05 mg/ml to 50 mg/ml. 
     
     
         8 . The composition of  claim 7 , wherein the therapeutically effective amount is at a range from 0.05 mg/ml to 5 mg/ml. 
     
     
         9 . The composition of  claim 1 , wherein the mucosa related disorder or disease comprises symptoms of ulceration, inflammatory, allergic reaction or bleeding. 
     
     
         10 . (canceled) 
     
     
         11 . The composition of  claim 1 , wherein the mucosa related disorder or disease is conjunctivitis, otitis, allergic rhinitis, gingivitis, oral ulcer, bronchitis, gastroesophageal reflux disease (GERD), esophagitis, gastritis, enteritis, irritable bowel syndrome (IBS), urethritis, cystitis or vaginitis. 
     
     
         12 . The composition of  claim 10 , wherein the enteritis is acute enteritis, chronic enteritis, infectious enteritis, ischemic enteritis, radioenteritis or drug induced enteritis. 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . The composition of  claim 10 , wherein the IBS is coeliac disease, fructose malabsorption, mild infections, parasitic infections like giardiasis, functional chronic constipation, diarrhea or chronic functional abdominal pain. 
     
     
         16 . The composition of  claim 1 , further comprising an excipient to formulate the composition in an administrating dosage form for eye, ear, oral, nose, respiratory tract, gastrointestinal tract or topical use. 
     
     
         17 . The composition of  claim 13 , wherein the administrating dosage form for oral use is selected from the group consisting of solid dosage form, solution, tablet including controlled-release tablet, and capsule. 
     
     
         18 . The composition of  claim 13 , wherein the administrating dosage form for gastrointestinal tract use is selected from the group consisting of solid dosage form, perfusion, enema, suppository, and solution including suspension. 
     
     
         19 . The composition of  claim 13 , wherein the administrating dosage form for topical use is selected from the group consisting of perfusion, enema, suppository, spray, inhalation and drop. 
     
     
         20 . The composition of  claim 1 , wherein the hyaluronic acid composition is in a solid dosage form and the therapeutic effective amount of the hyaluronic acid composition is between 50 mg and 1000 mg hyaluronic acids per day. 
     
     
         21 . The composition of  claim 10 , wherein allergic rhinitis or bronchitis can be treated by the composition as an adjuvant conjunctively used with a drug of antihistamine, antiallergic, anticongestives, steroid or antiasthma. 
     
     
         22 . The composition of  claim 11 , wherein enteritis can be treated by the composition as an adjuvant conjunctively used with a drug of antibiotic or antispasmodic. 
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . The composition of  claim 12 , wherein IBS can be treated by the composition as an adjuvant conjunctively used with a drug of antiallergic, antispasmodic, antidiarrheal, neurolytic, tranquilizer, analgesic, antidepressant or serotonin antagonist.