Methods for treating and preventing mucositis

Abstract

Methods for treating and preventing mucositis, in particular mucositis following the administration of chemotherapy drugs or a combination of said drugs with radiotherapy, are disclosed herein. More specifically, disclosed herein is the administration of a therapeutically effective amount of at least one of an anthocyanoside, a proanthocyanidin, or an extract containing at least one of an anthocyanoside or a proanthocyanidin for the treatment or prevention of mucositis. The therapeutically effective amount of the anthocyanoside, proanthocyanidin or extract can be administered alone or in combination with a therapeutically effective amount of at least one of an anti-inflammatory agent, immunomodulating agent, analgesic, antimicrobial agent or antifungal agent. Also disclosed herein are pharmaceutical compositions for treating and preventing mucositis.

1 . A method for the treatment of mucositis in a patient comprising administering to the patient a therapeutically effective amount of at least one of an anthocyanoside, a proanthocyanidin, or an extract comprising at least one of an anthocyanoside or a proanthocyanidin for the treatment of mucositis. 
   
   
       2 . The method of  claim 1 , wherein the anthocyanoside comprises a glycoside of a cyanidin, a delphinidin or a pelargonidin; or an aglycone of a glycoside of a cyanidin, a delphinidin or a pelargonidin. 
   
   
       3 . The method of  claim 1 , wherein the extract comprises a plant extract comprising a glycoside of a cyanidin, a delphinidin or a pelargonidin; or an aglycone of a glycoside of a cyanidin, a delphinidin or a pelargonidin. 
   
   
       4 . The method of  claim 1 , wherein the proanthocyanidin comprises proanthocyanidin A2 or proanthocyanidin B2. 
   
   
       5 . The method of  claim 1 , wherein the extract comprises a plant extract comprising proanthocyanidin A2 or proanthocyanidin B2. 
   
   
       6 . The method of  claim 1 , wherein the extract is derived from  Vaccinium myrtillus  or  Vitis vinifera.    
   
   
       7 . The method of  claim 1  further comprising administering a therapeutically effective amount of at least one of an anti-inflammatory agent, immunomodulating agent, analgesic, antimicrobial agent or antifungal agent. 
   
   
       8 . The method of  claim 7 , wherein the anti-inflammatory agent, immunomodulating agent or analgesic comprises an andrographolide or a natural or synthetic analogue thereof, a lactone sesquiterpene or a natural or synthetic analogue thereof, a parthenolide or a natural or synthetic analogue thereof, a cynaropicrin or a natural or synthetic analogue thereof, a isobutylamide of a polyunsaturated fatty acid, or an extract of  Zanthoxylum bungeanum  or  Echinacea angustofolia.    
   
   
       9 . The method of  claim 7 , wherein the antimicrobial agent or antifungal agent is natural or synthetic. 
   
   
       10 . The method of  claim 7 , wherein the antimicrobial agent or antifungal agent comprises miconazole, an antibiotic, a benzofuran, an isoquinoline alkaloid, or an extract comprising miconazole, a benzofuran, or an isoquinoline alkaloid. 
   
   
       11 . The method of  claim 7 , wherein the antimicrobial agent or antifungal agent comprises a benzophenanthridine alkaloid or an extract comprising benzophenanthridine alkaloid. 
   
   
       12 . The method of  claim 7 , wherein the antimicrobial agent or antifungal agent comprises sanguinarine or a natural or synthetic analogue thereof, chelerythrine or a natural or synthetic analogue thereof, chelidonine or a natural or synthetic analogue thereof, eupomatenoid or a natural or synthetic analogue thereof, or an extract of  Sanguinaria canadensis, Macleaya cordata  or  Macleaya microcarpa.    
   
   
       13 . The method of  claim 1 , wherein the therapeutically effective amount of the at least one anthocyanoside, proanthocyanidin or extract is about 50 mg to about 500 mg per unit dose. 
   
   
       14 . The method of  claim 1 , wherein the therapeutically effective amount of the at least one anthocyanoside, proanthocyanidin or extract is about 3000 mg or less per day. 
   
   
       15 . The method of  claim 1 , wherein the therapeutically effective amount of the at least one anthocyanoside, proanthocyanidin or extract is administered to the patient by systemic administration. 
   
   
       16 . The method of  claim 1 , wherein the therapeutically effective amount of the at least one anthocyanoside, proanthocyanidin or extract is administered to the patient by oral or topical administration. 
   
   
       17 . The method of  claim 7 , wherein the therapeutically effective amount of the antimicrobial agent or the antifungal agent is administered to the patient by systemic administration. 
   
   
       18 . The method of  claim 7 , wherein the therapeutically effective amount of the antimicrobial agent or the antifungal agent is administered to the patient by oral or topical administration. 
   
   
       19 . The method of  claim 1 , wherein the method comprises administering a pharmaceutical composition comprising (1) the therapeutically effective amount of the at least one anthocyanoside, proanthocyanidin or extract, and (2) a pharmaceutically acceptable excipient. 
   
   
       20 . The method of  claim 19 , wherein the pharmaceutical composition is in the form of a tablet, a capsule, a chewing gum, a liquid form, a vaginal gel or granulates. 
   
   
       21 . The method of  claim 19 , wherein the pharmaceutical composition is in the form of a tablet and the therapeutically effective amount of the at least one anthocyanoside, proanthocyanidin or extract is contained in the tablet in an amount of about 10 mg to about 200 mg per tablet. 
   
   
       22 . The method of  claim 19 , wherein the pharmaceutical composition is in the form of a tablet and the tablet further comprises a therapeutically effective amount of a antimicrobial agent or antifungal agent in an amount of about 2 mg to about 10 mg per tablet. 
   
   
       23 . The method of  claim 19 , wherein the pharmaceutical composition is in the form of a slow-dissolving tablet, and the extract comprises an extract of Vaccinium myrtillus, and wherein the pharmaceutical composition further comprises an isoquinoline alkaloid extracted from  Sanguinaria canadensis, Macleaya cordata  or  Macleaya microcarpa  and a lipophilic extract of  Zanthoxylum bungeanum.    
   
   
       24 . The method of  claim 1 , wherein the mucositis occurs in a part of the patient's gastroenteric tract. 
   
   
       25 . The method of  claim 1 , wherein the mucositis occurs in the patient's mouth, esophagus, stomach, intestine, colon, sex organ or skin. 
   
   
       26 . The method of  claim 1 , wherein the mucositis occurs in the patient's mouth. 
   
   
       27 . The method of  claim 1 , wherein the patient has a cancer. 
   
   
       28 . The method of  claim 1 , wherein the mucositis occurs in connection with the administration of a chemotherapy or a radiotherapy to the patient. 
   
   
       29 . The method of  claim 1 , wherein the mucositis occurs in connection with the administration of a chemotherapy comprising the administration of an anthracycline, fluorouracyl, paclitaxel, actinomycin, mithramycin, etoposide, topotecan, amsacrine, methotrexate, hydroxyurea or a platinum complex. 
   
   
       30 . The method of  claim 1 , wherein the therapeutically effective amount of the at least one anthocyanoside, proanthocyanidin or extract is administered to the patient before the patient receives a chemotherapy. 
   
   
       31 . The method of  claim 1 , wherein the therapeutically effective amount of the at least one anthocyanoside, proanthocyanidin or extract is administered to the patient while the patient receives a chemotherapy. 
   
   
       32 . The method of  claim 1 , wherein the therapeutically effective amount of the at least one anthocyanoside, proanthocyanidin or extract is administered to the patient after the patient receives a chemotherapy. 
   
   
       33 . The method of  claim 1 , wherein the mucositis occurs in a sex organ of the patient and the method further comprises administering a therapeutically effective amount of a benzophenanthridine alkaloid, a benzofuran, a hyperforin or an analogue thereof, or a fluoroglucinol or an analogue thereof. 
   
   
       34 . A method for the prevention of mucositis in a patient comprising administering to the patient a therapeutically effective amount of at least one of an anthocyanoside, a proanthocyanidin, or an extract comprising at least one of an anthocyanoside or a proanthocyanidin for the prevention of mucositis. 
   
   
       35 . The method of  claim 34 , wherein the anthocyanoside comprises a glycoside of a cyanidin, a delphinidin or a pelargonidin; or an aglycone of a glycoside of a cyanidin, a delphinidin or a pelargonidin 
   
   
       36 . The method of  claim 34 , wherein the extract comprises a plant extract comprising a glycoside of a cyanidin, a delphinidin or a pelargonidin; or an aglycone of a glycoside of a cyanidin, a delphinidin or a pelargonidin. 
   
   
       37 . The method of  claim 34 , wherein the proanthocyanidin comprises proanthocyanidin A2 or proanthocyanidin B2. 
   
   
       38 . The method of  claim 34 , wherein the extract comprises a plant extract comprising proanthocyanidin A2 or proanthocyanidin B2. 
   
   
       39 . The method of  claim 34 , wherein the extract is derived from  Vaccinium myrtillus  or  Vitis vinifera.    
   
   
       40 . The method of  claim 34  further comprising administering a therapeutically effective amount of at least one of an anti-inflammatory agent, immunomodulating agent, analgesic, antimicrobial agent or antifungal agent. 
   
   
       41 . The method of  claim 40 , wherein the anti-inflammatory agent, immunomodulating agent or analgesic comprises an andrographolide or a natural or synthetic analogue thereof, a lactone sesquiterpene or a natural or synthetic analogue thereof, a parthenolide or a natural or synthetic analogue thereof, a cynaropicrin or a natural or synthetic analogue thereof, a isobutylamide of a polyunsaturated fatty acid, or an extract of  Zanthoxylum bungeanum  or  Echinacea angustofolia.    
   
   
       42 . The method of  claim 40 , wherein the antimicrobial agent or antifungal agent is natural or synthetic. 
   
   
       43 . The method of  claim 40 , wherein the antimicrobial agent or antifungal agent comprises miconazole, an antibiotic, a benzofuran, an isoquinoline alkaloid, or an extract comprising miconazole, a benzofuran, or an isoquinoline alkaloid. 
   
   
       44 . The method of  claim 40 , wherein the antimicrobial agent or antifungal agent comprises a benzophenanthridine alkaloid or an extract comprising benzophenanthridine alkaloid. 
   
   
       45 . The method of  claim 40 , wherein the antimicrobial agent or antifungal agent comprises sanguinarine or a natural or synthetic analogue thereof, chelerythrine or a natural or synthetic analogue thereof, chelidonine or a natural or synthetic analogue thereof, eupomatenoid or a natural or synthetic analogue thereof, or an extract of  Sanguinaria canadensis, Macleaya cordata  or  Macleaya microcarpa.    
   
   
       46 . The method of  claim 34 , wherein the therapeutically effective amount of the at least one anthocyanoside, proanthocyanidin or extract is about 50 mg to about 500 mg per unit dose. 
   
   
       47 . The method of  claim 34 , wherein the therapeutically effective amount of the at least one anthocyanoside, proanthocyanidin or extract is about 3000 mg or less per day. 
   
   
       48 . The method of  claim 34 , wherein the therapeutically effective amount of the at least one anthocyanoside, proanthocyanidin or extract is administered to the patient by systemic administration. 
   
   
       49 . The method of  claim 34 , wherein the therapeutically effective amount of the at least one anthocyanoside, proanthocyanidin or extract is administered to the patient by oral or topical administration. 
   
   
       50 . The method of  claim 40 , wherein the therapeutically effective amount of the antimicrobial agent or the antifungal agent is administered to the patient by systemic administration. 
   
   
       51 . The method of  claim 40 , wherein the therapeutically effective amount of the antimicrobial agent or the antifungal agent is administered to the patient by oral or topical administration. 
   
   
       52 . The method of  claim 34 , wherein the method comprises administering a pharmaceutical composition comprising (1) the therapeutically effective amount of the at least one anthocyanoside, proanthocyanidin or extract, and (2) a pharmaceutically acceptable excipient. 
   
   
       53 . The method of  claim 52 , wherein the pharmaceutical composition is in the form of a tablet, a capsule, a chewing gum, a liquid form, a vaginal gel or granulates. 
   
   
       54 . The method of  claim 52 , wherein the pharmaceutical composition is in the form of a tablet and the therapeutically effective amount of the at least one anthocyanoside, proanthocyanidin or extract is contained in the tablet in an amount of about 10 mg to about 200 mg per tablet. 
   
   
       55 . The method of  claim 52 , wherein the pharmaceutical composition is in the form of a tablet and the tablet further comprises a therapeutically effective amount of a antimicrobial agent or antifungal agent in an amount of about 2 mg to about 10 mg per tablet. 
   
   
       56 . The method of  claim 52 , wherein the pharmaceutical composition is in the form of a slow-dissolving tablet, and the extract comprises an extract of Vaccinium myrtillus, and wherein the pharmaceutical composition further comprises an isoquinoline alkaloid extracted from  Sanguinaria canadensis, Macleaya cordata  or  Macleaya microcarpa  and a lipophilic extract of  Zanthoxylum bungeanum.    
   
   
       57 . The method of  claim 34 , wherein the mucositis occurs in a part of the patient's gastroenteric tract. 
   
   
       58 . The method of  claim 34 , wherein the mucositis occurs in the patient's mouth, esophagus, stomach, intestine, colon, sex organ or skin. 
   
   
       59 . The method of  claim 34 , wherein the mucositis occurs in the patient's mouth. 
   
   
       60 . The method of  claim 34 , wherein the patient has a cancer. 
   
   
       61 . The method of  claim 34 , wherein the mucositis occurs in connection with the administration of a chemotherapy or a radiotherapy to the patient. 
   
   
       62 . The method of  claim 34 , wherein the mucositis occurs in connection with the administration of a chemotherapy comprising the administration of an anthracycline, fluorouracyl, paclitaxel, actinomycin, mithramycin, etoposide, topotecan, amsacrine, methotrexate, hydroxyurea or a platinum complex. 
   
   
       63 . The method of  claim 34 , wherein the therapeutically effective amount of the at least one anthocyanoside, proanthocyanidin or extract is administered to the patient before the patient receives a chemotherapy. 
   
   
       64 . The method of  claim 34 , wherein the therapeutically effective amount of the at least one anthocyanoside, proanthocyanidin or extract is administered to the patient while the patient receives a chemotherapy. 
   
   
       65 . The method of  claim 34 , wherein the therapeutically effective amount of the at least one anthocyanoside, proanthocyanidin or extract is administered to the patient after the patient receives a chemotherapy. 
   
   
       66 . The method of  claim 34 , wherein the mucositis occurs in a sex organ of the patient and the method further comprises administering a therapeutically effective amount of a benzophenanthridine alkaloid, a benzofuran, a hyperforin or an analogue thereof, or a fluoroglucinol or an analogue thereof. 
   
   
       67 . A pharmaceutical composition for the treatment or prevention of mucositis comprising (1) a therapeutically effective amount of at least one of an anthocyanoside, a proanthocyanidin, or an extract comprising at least one of an anthocyanoside or a proanthocyanidin, and (2) a pharmaceutically acceptable excipient. 
   
   
       68 . The composition of  claim 67 , wherein the anthocyanoside comprises a glycoside of a cyanidin, a delphinidin or a pelargonidin; or an aglycone of a glycoside of a cyanidin, a delphinidin or a pelargonidin. 
   
   
       69 . The composition of  claim 67 , wherein the extract comprises a plant extract comprising a glycoside of a cyanidin, a delphinidin or a pelargonidin; or an aglycone of a glycoside of a cyanidin, a delphinidin or a pelargonidin. 
   
   
       70 . The composition of  claim 67 , wherein the proanthocyanidin comprises proanthocyanidin A2 or proanthocyanidin B2. 
   
   
       71 . The composition of  claim 67 , wherein the extract comprises a plant extract comprising proanthocyanidin A2 or proanthocyanidin B2. 
   
   
       72 . The composition of  claim 67 , wherein the extract is derived from  Vaccinium myrtillus  or  Vitis vinifera.    
   
   
       73 . The composition of  claim 67  further comprising a therapeutically effective amount of at least one of an anti-inflammatory agent, immunomodulating agent, analgesic, antimicrobial agent or antifungal agent. 
   
   
       74 . The composition of  claim 73 , wherein the anti-inflammatory agent, immunomodulating agent or analgesic comprises an andrographolide or a natural or synthetic analogue thereof, a lactone sesquiterpene or a natural or synthetic analogue thereof, a parthenolide or a natural or synthetic analogue thereof, a cynaropicrin or a natural or synthetic analogue thereof, a isobutylamide of a polyunsaturated fatty acid, or an extract of  Zanthoxylum bungeanum  or  Echinacea angustofolia.    
   
   
       75 . The composition of  claim 73 , wherein the antimicrobial agent or antifungal agent is natural or synthetic. 
   
   
       76 . The composition of  claim 73 , wherein the antimicrobial agent or antifungal agent comprises miconazole, an antibiotic, a benzofuran, an isoquinoline alkaloid, or an extract comprising miconazole, a benzofuran, or an isoquinoline alkaloid. 
   
   
       77 . The composition of  claim 73 , wherein the antimicrobial agent or antifungal agent comprises a benzophenanthridine alkaloid or an extract comprising benzophenanthridine alkaloid. 
   
   
       78 . The composition of  claim 73 , wherein the antimicrobial agent or antifungal agent comprises sanguinarine or a natural or synthetic analogue thereof, chelerythrine or a natural or synthetic analogue thereof, chelidonine or a natural or synthetic analogue thereof, eupomatenoid or a natural or synthetic analogue thereof, or an extract of  Sanguinaria canadensis, Macleaya cordata  or  Macleaya microcarpa.    
   
   
       79 . The composition of  claim 67 , wherein the therapeutically effective amount of the at least one anthocyanoside, proanthocyanidin or extract is about 50 mg to about 500 mg per unit dose. 
   
   
       80 . The composition of  claim 67 , wherein the therapeutically effective amount of the at least one anthocyanoside, proanthocyanidin or extract is about 3000 mg or less per day. 
   
   
       81 . The composition of  claim 67 , wherein the composition is suitable for systemic administration. 
   
   
       82 . The composition of  claim 67 , wherein composition is suitable for oral or topical administration. 
   
   
       83 . The composition of  claim 67 , wherein the composition is in the form of a tablet, a capsule, a chewing gum, a liquid form, a vaginal gel or granulates. 
   
   
       84 . The composition of  claim 67 , wherein the composition is a non-oral composition and the pharmaceutically acceptable excipient is suitable for non-oral administration. 
   
   
       85 . The composition of  claim 67 , wherein the composition is in the form of a tablet and the therapeutically effective amount of the at least one anthocyanoside, proanthocyanidin or extract is contained in the tablet in an amount of about 10 mg to about 200 mg per tablet. 
   
   
       86 . The composition of  claim 67 , wherein the composition is in the form of a tablet and the tablet further comprises a therapeutically effective amount of a antimicrobial agent or antifungal agent in an amount of about 2 mg to about 10 mg per tablet. 
   
   
       87 . The composition of  claim 67 , wherein the composition is in the form of a slow-dissolving tablet, and the extract comprises an extract of  Vaccinium myrtillus , and wherein the composition further comprises an isoquinoline alkaloid extracted from  Sanguinaria canadensis, Macleaya cordata  or  Macleaya microcarpa  and a lipophilic extract of  Zanthoxylum bungeanum.