Compositions

Abstract

The invention provides a colon cleansing solution comprising: a) 300 to 800 mmol per litre ascorbate anion provided by a mixture of: (i) ascorbic acid and (ii) one or more salts of ascorbic acid the components (i) and (ii) being present in a molar ratio of from 1:4.5 to 1:7.0; and b) 10 to 200 g per litre polyethylene glycol. The invention also provides methods an kits associated with, or making use of the solutions, and compositions for the preparation of the solutions.

1 . A method of cleansing the colon of a subject comprising:
 administering to the subject an effective amount of a first colon cleansing solution;   administering to the subject an effective amount of a second colon cleansing solution,   
       the second colon cleansing solution comprising: 
       a) 300 to 800 mmol per litre ascorbate anion provided by a mixture of:
 (i) ascorbic acid and 
 (ii) one or more salts of ascorbic acid 
 the components (i) and (ii) being present in a molar ratio of from 1:4.5 to 1:7.0; and 
 
       b) 10 to 200 g per litre polyethylene glycol. 
       whereby the first colon cleansing solution is taken over a time period t(d1) followed by optional additional clear fluid over a time period t(cf1), and then following a time interval t(dose interval), the second colon cleansing solution is taken over a time period t(d2) followed by optional additional clear fluid over a time period t(cf2), whereby the subject undergoes the surgical, therapeutic or diagnostic procedure at a time t 2  after the beginning of the colon cleansing method, and whereby the time interval after the completion of the second additional clear fluid and the start of the surgical, therapeutic or diagnostic procedure is t(procedure interval). 
     
     
         2 . A method as claimed in  claim 1  in which the subject ingests the first and second cleansing solutions on the day of the diagnostic, therapeutic or surgical procedure, and:
 t(d1) is 15 minutes to 1 hour (for example 30 minutes); 
 t(cf1) is 15 minutes to 1 hour (for example 30 minutes), 
 t(dose interval) is in the range of from 0 minutes to 8 hours (for example from 30 minutes to 4 hours, for example one hour or two hours) 
 t(d2) is 15 minutes to 1 hour (for example 30 minutes); 
 t(cf2) is 15 minutes to 1 hour (for example 30 minutes). 
 t 2  is in the range of from 3 to 14 hours (for example from 4 to 10 hours); and 
 t(procedure interval) is from 30 minutes to 10 hours (for example from 1 to 6 hours). 
 
     
     
         3 . A method as claimed in  claim 2  wherein the subject takes from 250 ml up to 1000 ml of the second cleansing solution. 
     
     
         4 . A method as claimed in  claim 2  wherein the subject takes from 400 ml up to 1100 ml of the first cleansing solution. 
     
     
         5 . A method as claimed in  claim 2  wherein first cleansing solution has a volume of 500 ml or 750 ml, and the second cleansing solution has a volume of 500 ml. 
     
     
         6 . A method as claimed in  claim 2  in which the subject takes additional clear fluid after one or both of the first and second colon cleansing solutions. 
     
     
         7 . A method as claimed in  claim 6 , in which the subject takes 300 ml to 1000 ml of additional clear fluid after each of the first and second colon cleansing solutions. 
     
     
         8 . A method as claimed in  claim 2  wherein:
 t(d1) is 30 minutes; 
 t(cf1) is 30 minutes; 
 t(dose interval) is in the range of from one hour or two hours; 
 t(d2) is 30 minutes; 
 t(cf2) is 30 minutes. 
 t 2  is in the range of from 4 to 8 hours; and 
 t(procedure interval) is from 1 to 6 hours. 
 
     
     
         9 . A method as claimed in  claim 1  in which the subject ingests the first and second cleansing solutions in the evening before the day of the diagnostic, therapeutic or surgical procedure, and:
 t(d1) is 15 minutes to 1 hour (for example 30 minutes); 
 t(cf1) is 15 minutes to 1 hour (for example 30 minutes), 
 t(dose interval) is in the range of from 0 minutes to 8 hours (for example from 30 minutes to 4 hours, for example one hour or two hours); 
 t(d2) is 15 minutes to 1 hour (for example 30 minutes); 
 t(cf2) is 15 minutes to 1 hour (for example 30 minutes). 
 t 2  is in the range of from 10 to 36 hours (for example from 12 to 24 hours, for example from 12 to 16 hours); and 
 t(procedure interval) is from 8 to 20 hours (for example from 10 to 16 hours). 
 
     
     
         10 . A method as claimed in  claim 9  wherein the subject takes from 250 ml up to 1000 ml of the second cleansing solution. 
     
     
         11 . A method as claimed in  claim 9  wherein the subject takes from 400 ml up to 1100 ml of the first cleansing solution. 
     
     
         12 . A method as claimed in  claim 9  wherein first cleansing solution has a volume of 500 ml or 750 ml, and the second cleansing solution has a volume of 500 ml. 
     
     
         13 . A method as claimed in  claim 9  wherein the subject takes additional clear fluid after one or both of the first and second colon cleansing solutions. 
     
     
         14 . A method as claimed in  claim 13 , in which the subject takes 300 ml to 1000 ml of additional clear fluid after each of the first and second colon cleansing solutions. 
     
     
         15 . A method as claimed in any one of  claims 9  to  14  wherein:
 t(d1) is 30 minutes; 
 t(cf1) is 30 minutes; 
 t(dose interval) is in the range of from one hour or two hours; 
 t(d2) is 30 minutes; 
 t(cf2) is 30 minutes. 
 t 2  is in the range of from 10 to 36 hours; and 
 t(procedure interval) is from 8 to 20 hours. 
 
     
     
         16 . A method as claimed in  claim 1  in which the subject ingests the first cleansing solution in the evening before the day of the diagnostic, therapeutic or surgical procedure, and the second cleansing solution in the evening before the day of the diagnostic, therapeutic or surgical procedure
 t(d1) is 15 minutes to 1 hour (for example 30 minutes); 
 t(cf1) is 15 minutes to 1 hour (for example 30 minutes), 
 t(dose interval) is in the range of from 8 to 20 hours (for example 10 to 14 hours); 
 t(d2) is 15 minutes to 1 hour (for example 30 minutes); 
 t(cf2) is 15 minutes to 1 hour (for example 30 minutes). 
 t 2  is in the range of from 10 to 36 hours (for example from 12 to 24 hours, for example from 12 to 16 hours); and 
 t(procedure interval) is from 30 minutes to 10 hours (for example from 1 to 6 hours). 
 
     
     
         17 . A method as claimed in  claim 16  wherein the subject takes from 250 ml up to 1000 ml of the second cleansing solution. 
     
     
         18 . A method as claimed in  claim 16  wherein the subject takes from 400 ml up to 1100 ml of the first cleansing solution. 
     
     
         19 . A method as claimed in  claim 18  wherein first cleansing solution has a volume of 500 ml or 750 ml, and the second cleansing solution has a volume of 500 ml. 
     
     
         20 . A method as claimed in  claim 16  wherein the subject takes additional clear fluid after one or both of the first and second colon cleansing solutions. 
     
     
         21 . A method as claimed in  claim 20 , in which the subject takes 300 ml to 1000 ml of additional clear fluid after each of the first and second colon cleansing solutions. 
     
     
         22 . A method as claimed in  claim 16  wherein:
 t(d1) is 30 minutes; 
 t(cf1) is 30 minutes; 
 t(dose interval) is in the range of from 8 to 20 hours; 
 t(d2) is 30 minutes; 
 t(cf2) is 30 minutes. 
 t 2  is in the range of from 10 to 36 hours; and 
 t(procedure interval) is from 1 to 6 hours. 
 
     
     
         23 . A method as claimed in  claim 1  in which the second colon cleansing solution comprises: 
       a)
 (iii) 12 to 20 g per litre ascorbic acid and 
 (iv) 80 to 120 g per litre sodium ascorbate 
 the components (i) and (ii) being present in a weight ratio of from 1:5063 to 1:7.875; 
 
       b) 60 to 100 g per litre PEG having an average molecular weight of 3000 to 4000 Da; 
       c) 3 to 8 g per litre sodium chloride and 1 to 7 g per litre potassium chloride; 
       e) one or more flavouring agents; and 
       f) one or more sweeteners. 
     
     
         24 . A method as claimed in  claim 1  in which the first colon cleansing solution comprises: 
       (i) 90 to 200 g per litre PEG having an average molecular weight of 2500 to 4500 Da. 
       (ii) 2.0 to 15 g per litre of one or more alkali metal sulphates, alkaline earth metal sulphates or a mixture thereof 
       (iii) 0.5 to 5.0 g per litre sodium chloride, and 0.05 to 5.0 g per litre potassium chloride; 
       (iv) one or more flavouring agents; and 
       (v) one or more sweeteners. 
     
     
         25 . A method as claimed in  claim 2  wherein the method is carried out on the day of a colonoscopy of a subject, and
 At approximately 05:00H, the subject takes solution S2 in 500 mL of water over 30 minutes at a rate of approximately 250 mL every 15 minutes; 
 The subject drinks 500 mL of additional water over the next 30 minutes at the rate of 250 mL every 15 minutes until complete; 
 Then a 1 hour liquid-free break is observed; 
 At approximately 07.00H, the subject takes solution T1 in 500 mL of water over 30 minutes at a rate of 250 mL every 15 minutes; 
 The subject drinks 500 mL of additional water; and 
 Colonoscopy is carried out at least one hour after the last of the additional water is consumed, 
 
       solution S2 being a solution comprising 100.00 g PEG 3350, 9.00 g Na 2 SO 4  (anhyd), 2.00 g NaCl, 1.00 g KCl, 0.40 g sucralose, 0.500 g Fruit Punch Flavouring and 0.75 g Citric Acid in water to a volume of 500 ml, and solution T1 being a solution comprising 40.00 g PEG 3350, 3.20 g NaCl, 1.20 g KCl, 1.93 g Aspartamel 0.60 g Orange Flavouring, 48.11 g Sodium Ascorbate and 7.54 g Ascorbic Acid in water to a volume of 500 ml. 
     
     
         26 . A method as claimed in  claim 9  wherein the method is carried out on the day before a colonoscopy of a subject, and
 At approximately 18:00H, the subject takes solution S2 in 500 mL of water over 30 minutes at a rate of approximately 250 mL every 15 minutes until complete; 
 The subject drinks 500 mL of additional water; 
 After an interval of 1-2 hours, the subject takes solution T1 in 500 mL of water over 30 minutes at the rate of 250 mL every 15 minutes until complete; 
 The subject drinks 500 mL of additional water; and 
 Colonoscopy is carried out the following day, 
 
       solution S2 being a solution comprising 100.00 g PEG 3350, 9.00 g Na 2 SO 4  (anhyd), 2.00 g NaCl, 1.00 g KCl, 0.40 g sucralose, 0.500 g Fruit Punch Flavouring and 0.75 g Citric Acid in water to a volume of 500 ml, and solution T1 being a solution comprising 40.00 g PEG 3350, 3.20 g NaCl, 1.20 g KCl, 1.93 g Aspartame 0.60 g Orange Flavouring, 48.11 g Sodium Ascorbate and 7.54 g Ascorbic Acid in water to a volume of 500 ml. 
     
     
         27 . A method as claimed in  claim 16  wherein on the day before the colonoscopy:
 At approximately 18:00H, the subject takes Formulation S2 in 16 fl oz (500 mL) of water; 
 The subject drinks 16 fl oz (500 mL) of mandatory additional water; 
 
       and, on the day of the colonoscopy:
 At approximately 06:00H, the subject takes Formulation T1 in 16 fl oz. (500 mL) of water over 30 minutes at the rate of 250 mL every 15 minutes until complete; 
 The subject drinks 500 mL of additional water; and 
 Colonoscopy is carried out at least one hour after the last of the additional water is consumed, 
 
       solution S2 being a solution comprising 100.00 g PEG 3350, 9.00 g Na 2 SO 4  (anhyd), 2.00 g NaCl, 1.00 g KCl, 0.40 g sucralose, 0.500 g Fruit Punch Flavouring and 0.75 g Citric Acid in water to a volume of 500 ml, and solution T1 being a solution comprising 40.00 g PEG 3350, 3.20 g NaCl, 1.20 g KCl, 1.93 g Aspartamel 0.60 g Orange Flavouring, 48.11 g Sodium Ascorbate and 7.54 g Ascorbic Acid in water to a volume of 500 ml. 
     
     
         28 . A method as claimed in  claim 1  in which the subject is advised not to eat heavy meals before starting the colon cleansing treatment, or the subject is advised to fast for 12 hours before starting the colon cleansing treatment, or the subject is advised to follow a “white diet” for a day before, or the day of the start of the colon cleansing procedure, or the subject is advised to consume only a light meal, for example plain yoghurt, during that period; 
       “white diet” being food intake restricted to white and cream-coloured foods, foods that are allowed including chicken breast without skin, fish fillets without skin, eggs, cheeses, rice crackers, white bread, plain pasta, white rice, rice noodle, peeled potato, ice cream, butter, custard, mayonnaise, milk and white chocolate; white foods that are not allowed including coconut, onion, cauliflower, pears, parsnip, semolina, banana and popcorn.