NZ723017B2 - Method of cleansing the colon - Google Patents
Method of cleansing the colon Download PDFInfo
- Publication number
- NZ723017B2 NZ723017B2 NZ723017A NZ72301715A NZ723017B2 NZ 723017 B2 NZ723017 B2 NZ 723017B2 NZ 723017 A NZ723017 A NZ 723017A NZ 72301715 A NZ72301715 A NZ 72301715A NZ 723017 B2 NZ723017 B2 NZ 723017B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- solution
- minutes
- subject
- hours
- per litre
- Prior art date
Links
- 210000001072 colon Anatomy 0.000 title claims abstract description 286
- 238000000034 method Methods 0.000 title claims abstract description 126
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims abstract description 498
- 239000000203 mixture Substances 0.000 claims abstract description 297
- 235000010323 ascorbic acid Nutrition 0.000 claims abstract description 249
- 239000011668 ascorbic acid Substances 0.000 claims abstract description 249
- 229960005070 ascorbic acid Drugs 0.000 claims abstract description 203
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 197
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 193
- CIWBSHSKHKDKBQ-JLAZNSOCSA-M L-ascorbate Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] CIWBSHSKHKDKBQ-JLAZNSOCSA-M 0.000 claims abstract description 97
- 150000003839 salts Chemical class 0.000 claims abstract description 95
- -1 alkaline earth metal sulphates Chemical class 0.000 claims abstract description 67
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims abstract description 56
- 238000001356 surgical procedure Methods 0.000 claims abstract description 46
- 238000002405 diagnostic procedure Methods 0.000 claims abstract description 41
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 35
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 35
- 229910052936 alkali metal sulfate Inorganic materials 0.000 claims abstract description 30
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 220
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 220
- 235000002639 sodium chloride Nutrition 0.000 claims description 208
- 235000003599 food sweetener Nutrition 0.000 claims description 175
- 239000003765 sweetening agent Substances 0.000 claims description 175
- 239000000796 flavoring agent Substances 0.000 claims description 145
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 126
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 111
- 239000001103 potassium chloride Substances 0.000 claims description 110
- 235000011164 potassium chloride Nutrition 0.000 claims description 110
- 239000011780 sodium chloride Substances 0.000 claims description 110
- 235000013355 food flavoring agent Nutrition 0.000 claims description 92
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 90
- 229960005055 sodium ascorbate Drugs 0.000 claims description 89
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 claims description 88
- 235000010378 sodium ascorbate Nutrition 0.000 claims description 88
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 claims description 88
- 108010011485 Aspartame Proteins 0.000 claims description 65
- 239000000605 aspartame Substances 0.000 claims description 65
- 235000010357 aspartame Nutrition 0.000 claims description 65
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 65
- 229960003438 aspartame Drugs 0.000 claims description 65
- 239000003792 electrolyte Substances 0.000 claims description 45
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 45
- 235000011152 sodium sulphate Nutrition 0.000 claims description 45
- 239000004376 Sucralose Substances 0.000 claims description 44
- 235000019408 sucralose Nutrition 0.000 claims description 44
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 claims description 44
- 238000011282 treatment Methods 0.000 claims description 38
- 238000002052 colonoscopy Methods 0.000 claims description 33
- 235000013399 edible fruits Nutrition 0.000 claims description 30
- 230000037406 food intake Effects 0.000 claims description 13
- 235000013361 beverage Nutrition 0.000 claims description 10
- 235000005911 diet Nutrition 0.000 claims description 9
- 230000037213 diet Effects 0.000 claims description 7
- 235000013305 food Nutrition 0.000 claims description 6
- 238000009472 formulation Methods 0.000 claims description 6
- 229940050929 polyethylene glycol 3350 Drugs 0.000 claims description 6
- 240000007594 Oryza sativa Species 0.000 claims description 4
- 235000007164 Oryza sativa Nutrition 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 235000012054 meals Nutrition 0.000 claims description 4
- 235000009566 rice Nutrition 0.000 claims description 4
- 241000251468 Actinopterygii Species 0.000 claims description 2
- 244000291564 Allium cepa Species 0.000 claims description 2
- 235000002732 Allium cepa var. cepa Nutrition 0.000 claims description 2
- 235000011299 Brassica oleracea var botrytis Nutrition 0.000 claims description 2
- 240000003259 Brassica oleracea var. botrytis Species 0.000 claims description 2
- 235000013162 Cocos nucifera Nutrition 0.000 claims description 2
- 244000060011 Cocos nucifera Species 0.000 claims description 2
- 240000002129 Malva sylvestris Species 0.000 claims description 2
- 235000006770 Malva sylvestris Nutrition 0.000 claims description 2
- 235000018290 Musa x paradisiaca Nutrition 0.000 claims description 2
- 240000004370 Pastinaca sativa Species 0.000 claims description 2
- 235000017769 Pastinaca sativa subsp sativa Nutrition 0.000 claims description 2
- 206010034203 Pectus Carinatum Diseases 0.000 claims description 2
- 241000220324 Pyrus Species 0.000 claims description 2
- 235000002595 Solanum tuberosum Nutrition 0.000 claims description 2
- 244000061456 Solanum tuberosum Species 0.000 claims description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 claims description 2
- 241000482268 Zea mays subsp. mays Species 0.000 claims description 2
- 235000014121 butter Nutrition 0.000 claims description 2
- 235000013351 cheese Nutrition 0.000 claims description 2
- 235000011950 custard Nutrition 0.000 claims description 2
- 235000013601 eggs Nutrition 0.000 claims description 2
- 235000012631 food intake Nutrition 0.000 claims description 2
- 235000015243 ice cream Nutrition 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 235000010746 mayonnaise Nutrition 0.000 claims description 2
- 239000008268 mayonnaise Substances 0.000 claims description 2
- 239000008267 milk Substances 0.000 claims description 2
- 210000004080 milk Anatomy 0.000 claims description 2
- 235000012149 noodles Nutrition 0.000 claims description 2
- 235000015927 pasta Nutrition 0.000 claims description 2
- 235000021017 pears Nutrition 0.000 claims description 2
- 235000019685 rice crackers Nutrition 0.000 claims description 2
- 235000012794 white bread Nutrition 0.000 claims description 2
- 235000019222 white chocolate Nutrition 0.000 claims description 2
- 235000019220 whole milk chocolate Nutrition 0.000 claims description 2
- 235000013618 yogurt Nutrition 0.000 claims description 2
- 240000008790 Musa x paradisiaca Species 0.000 claims 1
- 239000012530 fluid Substances 0.000 abstract description 90
- 239000000243 solution Substances 0.000 description 566
- 239000003599 detergent Substances 0.000 description 48
- 229940072107 ascorbate Drugs 0.000 description 46
- 239000000843 powder Substances 0.000 description 46
- 239000003795 chemical substances by application Substances 0.000 description 42
- 229910021653 sulphate ion Inorganic materials 0.000 description 42
- 235000015165 citric acid Nutrition 0.000 description 39
- 235000019634 flavors Nutrition 0.000 description 38
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 34
- 238000002360 preparation method Methods 0.000 description 30
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 26
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
- 239000000619 acesulfame-K Substances 0.000 description 26
- 229910052783 alkali metal Inorganic materials 0.000 description 26
- 229940074358 magnesium ascorbate Drugs 0.000 description 25
- AIOKQVJVNPDJKA-ZZMNMWMASA-L magnesium;(2r)-2-[(1s)-1,2-dihydroxyethyl]-4-hydroxy-5-oxo-2h-furan-3-olate Chemical compound [Mg+2].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] AIOKQVJVNPDJKA-ZZMNMWMASA-L 0.000 description 25
- 150000001340 alkali metals Chemical class 0.000 description 24
- 235000019640 taste Nutrition 0.000 description 21
- 241000124008 Mammalia Species 0.000 description 20
- 240000000560 Citrus x paradisi Species 0.000 description 19
- 229920002562 Polyethylene Glycol 3350 Polymers 0.000 description 18
- 239000011734 sodium Substances 0.000 description 18
- 235000005979 Citrus limon Nutrition 0.000 description 17
- 244000131522 Citrus pyriformis Species 0.000 description 17
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 16
- 229940017794 potassium ascorbate Drugs 0.000 description 16
- 229910052708 sodium Inorganic materials 0.000 description 16
- 239000004260 Potassium ascorbate Substances 0.000 description 15
- 239000002775 capsule Substances 0.000 description 15
- 235000019275 potassium ascorbate Nutrition 0.000 description 15
- CONVKSGEGAVTMB-RXSVEWSESA-M potassium-L-ascorbate Chemical compound [K+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] CONVKSGEGAVTMB-RXSVEWSESA-M 0.000 description 15
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 14
- 235000011941 Tilia x europaea Nutrition 0.000 description 14
- 235000010358 acesulfame potassium Nutrition 0.000 description 14
- 239000004571 lime Substances 0.000 description 14
- 239000007968 orange flavor Substances 0.000 description 14
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
- 235000019341 magnesium sulphate Nutrition 0.000 description 13
- 238000002156 mixing Methods 0.000 description 13
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 13
- 229910052939 potassium sulfate Inorganic materials 0.000 description 13
- 239000001120 potassium sulphate Substances 0.000 description 13
- 235000011151 potassium sulphates Nutrition 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 12
- 235000004936 Bromus mango Nutrition 0.000 description 12
- 241001093152 Mangifera Species 0.000 description 12
- 235000014826 Mangifera indica Nutrition 0.000 description 12
- 235000009184 Spondias indica Nutrition 0.000 description 12
- 229960004998 acesulfame potassium Drugs 0.000 description 12
- 235000019600 saltiness Nutrition 0.000 description 12
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 11
- 229910052700 potassium Inorganic materials 0.000 description 11
- 239000011591 potassium Substances 0.000 description 11
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 11
- 241000207199 Citrus Species 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 235000020971 citrus fruits Nutrition 0.000 description 10
- 229940030786 moviprep Drugs 0.000 description 10
- 229960003975 potassium Drugs 0.000 description 10
- 239000002253 acid Substances 0.000 description 9
- 239000011248 coating agent Substances 0.000 description 9
- 238000000576 coating method Methods 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
- 238000005538 encapsulation Methods 0.000 description 8
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 8
- 239000008279 sol Substances 0.000 description 8
- 206010047700 Vomiting Diseases 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 7
- 239000008143 stimulant laxative Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 230000008673 vomiting Effects 0.000 description 7
- 244000099147 Ananas comosus Species 0.000 description 6
- 235000007119 Ananas comosus Nutrition 0.000 description 6
- 235000016623 Fragaria vesca Nutrition 0.000 description 6
- 240000009088 Fragaria x ananassa Species 0.000 description 6
- 235000011363 Fragaria x ananassa Nutrition 0.000 description 6
- 150000000994 L-ascorbates Chemical class 0.000 description 6
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 6
- 240000001890 Ribes hudsonianum Species 0.000 description 6
- 235000016954 Ribes hudsonianum Nutrition 0.000 description 6
- 235000001466 Ribes nigrum Nutrition 0.000 description 6
- 235000009499 Vanilla fragrans Nutrition 0.000 description 6
- 235000012036 Vanilla tahitensis Nutrition 0.000 description 6
- YVPYQUNUQOZFHG-UHFFFAOYSA-N amidotrizoic acid Chemical compound CC(=O)NC1=C(I)C(NC(C)=O)=C(I)C(C(O)=O)=C1I YVPYQUNUQOZFHG-UHFFFAOYSA-N 0.000 description 6
- 239000000975 dye Substances 0.000 description 6
- 238000011049 filling Methods 0.000 description 6
- 239000003205 fragrance Substances 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 229940126602 investigational medicinal product Drugs 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000011777 magnesium Substances 0.000 description 6
- 229910052749 magnesium Inorganic materials 0.000 description 6
- 229940091250 magnesium supplement Drugs 0.000 description 6
- 230000003204 osmotic effect Effects 0.000 description 6
- 238000005192 partition Methods 0.000 description 6
- BUKHSQBUKZIMLB-UHFFFAOYSA-L potassium;sodium;dichloride Chemical compound [Na+].[Cl-].[Cl-].[K+] BUKHSQBUKZIMLB-UHFFFAOYSA-L 0.000 description 6
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 6
- 229940083542 sodium Drugs 0.000 description 6
- 229910052788 barium Inorganic materials 0.000 description 5
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 5
- 230000000112 colonic effect Effects 0.000 description 5
- 235000008504 concentrate Nutrition 0.000 description 5
- 239000012141 concentrate Substances 0.000 description 5
- 239000002872 contrast media Substances 0.000 description 5
- 239000002360 explosive Substances 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 239000002002 slurry Substances 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 235000020354 squash Nutrition 0.000 description 5
- 235000000346 sugar Nutrition 0.000 description 5
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 4
- 235000009434 Actinidia chinensis Nutrition 0.000 description 4
- 244000298697 Actinidia deliciosa Species 0.000 description 4
- 235000009436 Actinidia deliciosa Nutrition 0.000 description 4
- KHOITXIGCFIULA-UHFFFAOYSA-N Alophen Chemical compound C1=CC(OC(=O)C)=CC=C1C(C=1N=CC=CC=1)C1=CC=C(OC(C)=O)C=C1 KHOITXIGCFIULA-UHFFFAOYSA-N 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 4
- 206010010774 Constipation Diseases 0.000 description 4
- PHOQVHQSTUBQQK-SQOUGZDYSA-N D-glucono-1,5-lactone Chemical compound OC[C@H]1OC(=O)[C@H](O)[C@@H](O)[C@@H]1O PHOQVHQSTUBQQK-SQOUGZDYSA-N 0.000 description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
- 241000792859 Enema Species 0.000 description 4
- 206010056325 Faecaloma Diseases 0.000 description 4
- IMQLKJBTEOYOSI-GPIVLXJGSA-N Inositol-hexakisphosphate Chemical compound OP(O)(=O)O[C@H]1[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H]1OP(O)(O)=O IMQLKJBTEOYOSI-GPIVLXJGSA-N 0.000 description 4
- IMQLKJBTEOYOSI-UHFFFAOYSA-N Phytic acid Natural products OP(O)(=O)OC1C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C1OP(O)(O)=O IMQLKJBTEOYOSI-UHFFFAOYSA-N 0.000 description 4
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 4
- 235000011054 acetic acid Nutrition 0.000 description 4
- 150000001342 alkaline earth metals Chemical class 0.000 description 4
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
- 229960000503 bisacodyl Drugs 0.000 description 4
- 229960002875 bisoxatin Drugs 0.000 description 4
- BPKUDUSVDVLOPY-UHFFFAOYSA-N bisoxatin Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C(=O)NC2=CC=CC=C2O1 BPKUDUSVDVLOPY-UHFFFAOYSA-N 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 229960005069 calcium Drugs 0.000 description 4
- 229940039231 contrast media Drugs 0.000 description 4
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 description 4
- 229940095399 enema Drugs 0.000 description 4
- 239000007920 enema Substances 0.000 description 4
- 239000003623 enhancer Substances 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 230000008014 freezing Effects 0.000 description 4
- 238000007710 freezing Methods 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 235000012209 glucono delta-lactone Nutrition 0.000 description 4
- 239000000182 glucono-delta-lactone Substances 0.000 description 4
- 229960003681 gluconolactone Drugs 0.000 description 4
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 4
- 239000004310 lactic acid Substances 0.000 description 4
- 235000014655 lactic acid Nutrition 0.000 description 4
- 239000008141 laxative Substances 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- 239000001630 malic acid Substances 0.000 description 4
- 235000011090 malic acid Nutrition 0.000 description 4
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 4
- 229960000907 methylthioninium chloride Drugs 0.000 description 4
- 235000011007 phosphoric acid Nutrition 0.000 description 4
- 229940068041 phytic acid Drugs 0.000 description 4
- 239000000467 phytic acid Substances 0.000 description 4
- 235000002949 phytic acid Nutrition 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 238000002579 sigmoidoscopy Methods 0.000 description 4
- 150000008163 sugars Chemical class 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 239000011975 tartaric acid Substances 0.000 description 4
- 235000002906 tartaric acid Nutrition 0.000 description 4
- 208000035143 Bacterial infection Diseases 0.000 description 3
- 244000025596 Cassia laevigata Species 0.000 description 3
- 235000006693 Cassia laevigata Nutrition 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 244000290333 Vanilla fragrans Species 0.000 description 3
- 244000263375 Vanilla tahitensis Species 0.000 description 3
- 210000001015 abdomen Anatomy 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 210000000436 anus Anatomy 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 208000022362 bacterial infectious disease Diseases 0.000 description 3
- 235000021028 berry Nutrition 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 3
- 235000012730 carminic acid Nutrition 0.000 description 3
- 239000004106 carminic acid Substances 0.000 description 3
- 239000004359 castor oil Substances 0.000 description 3
- 235000019438 castor oil Nutrition 0.000 description 3
- 229960001777 castor oil Drugs 0.000 description 3
- 235000009508 confectionery Nutrition 0.000 description 3
- 239000008151 electrolyte solution Substances 0.000 description 3
- 229940021013 electrolyte solution Drugs 0.000 description 3
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 3
- 230000036571 hydration Effects 0.000 description 3
- 238000006703 hydration reaction Methods 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 230000002101 lytic effect Effects 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 210000004877 mucosa Anatomy 0.000 description 3
- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 210000000664 rectum Anatomy 0.000 description 3
- 229940124513 senna glycoside Drugs 0.000 description 3
- CEZCCHQBSQPRMU-LLIZZRELSA-L Allura red AC Chemical compound [Na+].[Na+].COC1=CC(S([O-])(=O)=O)=C(C)C=C1\N=N\C1=C(O)C=CC2=CC(S([O-])(=O)=O)=CC=C12 CEZCCHQBSQPRMU-LLIZZRELSA-L 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 102000016911 Deoxyribonucleases Human genes 0.000 description 2
- 108010053770 Deoxyribonucleases Proteins 0.000 description 2
- 206010014418 Electrolyte imbalance Diseases 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 239000004214 Fast Green FCF Substances 0.000 description 2
- RZSYLLSAWYUBPE-UHFFFAOYSA-L Fast green FCF Chemical compound [Na+].[Na+].C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C(=CC(O)=CC=2)S([O-])(=O)=O)C=CC=1N(CC)CC1=CC=CC(S([O-])(=O)=O)=C1 RZSYLLSAWYUBPE-UHFFFAOYSA-L 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- ZRWPUFFVAOMMNM-UHFFFAOYSA-N Patulin Chemical compound OC1OCC=C2OC(=O)C=C12 ZRWPUFFVAOMMNM-UHFFFAOYSA-N 0.000 description 2
- 229920002594 Polyethylene Glycol 8000 Polymers 0.000 description 2
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 2
- 244000269722 Thea sinensis Species 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 235000012741 allura red AC Nutrition 0.000 description 2
- 239000004191 allura red AC Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 235000012733 azorubine Nutrition 0.000 description 2
- 235000012677 beetroot red Nutrition 0.000 description 2
- 239000001654 beetroot red Substances 0.000 description 2
- 235000010376 calcium ascorbate Nutrition 0.000 description 2
- 229940047036 calcium ascorbate Drugs 0.000 description 2
- 239000011692 calcium ascorbate Substances 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- BLORRZQTHNGFTI-ZZMNMWMASA-L calcium-L-ascorbate Chemical compound [Ca+2].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] BLORRZQTHNGFTI-ZZMNMWMASA-L 0.000 description 2
- OIQPTROHQCGFEF-UHFFFAOYSA-L chembl1371409 Chemical compound [Na+].[Na+].OC1=CC=C2C=C(S([O-])(=O)=O)C=CC2=C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 OIQPTROHQCGFEF-UHFFFAOYSA-L 0.000 description 2
- 239000000306 component Substances 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 235000012754 curcumin Nutrition 0.000 description 2
- 239000004148 curcumin Substances 0.000 description 2
- 229940109262 curcumin Drugs 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 229960005423 diatrizoate Drugs 0.000 description 2
- 230000000378 dietary effect Effects 0.000 description 2
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 description 2
- 239000004205 dimethyl polysiloxane Substances 0.000 description 2
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 2
- AMTWCFIAVKBGOD-UHFFFAOYSA-N dioxosilane;methoxy-dimethyl-trimethylsilyloxysilane Chemical compound O=[Si]=O.CO[Si](C)(C)O[Si](C)(C)C AMTWCFIAVKBGOD-UHFFFAOYSA-N 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000001839 endoscopy Methods 0.000 description 2
- SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 description 2
- 235000019240 fast green FCF Nutrition 0.000 description 2
- 210000003608 fece Anatomy 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 239000008233 hard water Substances 0.000 description 2
- 235000012738 indigotine Nutrition 0.000 description 2
- 239000004179 indigotine Substances 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- NBQNWMBBSKPBAY-UHFFFAOYSA-N iodixanol Chemical compound IC=1C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C(I)C=1N(C(=O)C)CC(O)CN(C(C)=O)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NBQNWMBBSKPBAY-UHFFFAOYSA-N 0.000 description 2
- NTHXOOBQLCIOLC-UHFFFAOYSA-N iohexol Chemical compound OCC(O)CN(C(=O)C)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NTHXOOBQLCIOLC-UHFFFAOYSA-N 0.000 description 2
- XQZXYNRDCRIARQ-LURJTMIESA-N iopamidol Chemical compound C[C@H](O)C(=O)NC1=C(I)C(C(=O)NC(CO)CO)=C(I)C(C(=O)NC(CO)CO)=C1I XQZXYNRDCRIARQ-LURJTMIESA-N 0.000 description 2
- UUMLTINZBQPNGF-UHFFFAOYSA-N ioxilan Chemical compound OCC(O)CN(C(=O)C)C1=C(I)C(C(=O)NCCO)=C(I)C(C(=O)NCC(O)CO)=C1I UUMLTINZBQPNGF-UHFFFAOYSA-N 0.000 description 2
- 230000002475 laxative effect Effects 0.000 description 2
- 235000015122 lemonade Nutrition 0.000 description 2
- 235000020094 liqueur Nutrition 0.000 description 2
- 229960003511 macrogol Drugs 0.000 description 2
- 239000004337 magnesium citrate Substances 0.000 description 2
- 229960005336 magnesium citrate Drugs 0.000 description 2
- 235000002538 magnesium citrate Nutrition 0.000 description 2
- RGPGEMGZZATIQL-UHFFFAOYSA-H magnesium;dipotassium;disodium;trisulfate Chemical compound [Na+].[Na+].[Mg+2].[K+].[K+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O RGPGEMGZZATIQL-UHFFFAOYSA-H 0.000 description 2
- GGGDNPWHMNJRFN-UHFFFAOYSA-N metrizoic acid Chemical compound CC(=O)N(C)C1=C(I)C(NC(C)=O)=C(I)C(C(O)=O)=C1I GGGDNPWHMNJRFN-UHFFFAOYSA-N 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 235000019629 palatability Nutrition 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 2
- 235000012731 ponceau 4R Nutrition 0.000 description 2
- 239000004175 ponceau 4R Substances 0.000 description 2
- 229940059097 powder for oral solution Drugs 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- KXXXUIKPSVVSAW-UHFFFAOYSA-K pyranine Chemical compound [Na+].[Na+].[Na+].C1=C2C(O)=CC(S([O-])(=O)=O)=C(C=C3)C2=C2C3=C(S([O-])(=O)=O)C=C(S([O-])(=O)=O)C2=C1 KXXXUIKPSVVSAW-UHFFFAOYSA-K 0.000 description 2
- 229940021384 salt irrigating solution Drugs 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 229940083037 simethicone Drugs 0.000 description 2
- LMXOHSDXUQEUSF-YECHIGJVSA-N sinefungin Chemical compound O[C@@H]1[C@H](O)[C@@H](C[C@H](CC[C@H](N)C(O)=O)N)O[C@H]1N1C2=NC=NC(N)=C2N=C1 LMXOHSDXUQEUSF-YECHIGJVSA-N 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 235000021091 sugar-based sweeteners Nutrition 0.000 description 2
- 239000008399 tap water Substances 0.000 description 2
- 235000020679 tap water Nutrition 0.000 description 2
- PLSARIKBYIPYPF-UHFFFAOYSA-H trimagnesium dicitrate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O PLSARIKBYIPYPF-UHFFFAOYSA-H 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- NDDLLTAIKYHPOD-ISLYRVAYSA-N (2e)-6-chloro-2-(6-chloro-4-methyl-3-oxo-1-benzothiophen-2-ylidene)-4-methyl-1-benzothiophen-3-one Chemical compound S/1C2=CC(Cl)=CC(C)=C2C(=O)C\1=C1/SC(C=C(Cl)C=C2C)=C2C1=O NDDLLTAIKYHPOD-ISLYRVAYSA-N 0.000 description 1
- XLTMWFMRJZDFFD-UHFFFAOYSA-N 1-[(2-chloro-4-nitrophenyl)diazenyl]naphthalen-2-ol Chemical compound OC1=CC=C2C=CC=CC2=C1N=NC1=CC=C([N+]([O-])=O)C=C1Cl XLTMWFMRJZDFFD-UHFFFAOYSA-N 0.000 description 1
- JMEVHYCNAPFOAB-UHFFFAOYSA-N 2-(3-hydroxy-5-sulfo-1H-indol-2-yl)-3-oxoindole-5-sulfonic acid Chemical compound Oc1c([nH]c2ccc(cc12)S(O)(=O)=O)C1=Nc2ccc(cc2C1=O)S(O)(=O)=O JMEVHYCNAPFOAB-UHFFFAOYSA-N 0.000 description 1
- KAOXHXDKFGCWPK-UHFFFAOYSA-N 2-[[4-[bis(2-hydroxyethyl)amino]phenyl]diazenyl]benzoic acid Chemical compound C1=CC(N(CCO)CCO)=CC=C1N=NC1=CC=CC=C1C(O)=O KAOXHXDKFGCWPK-UHFFFAOYSA-N 0.000 description 1
- HMMGKOVEOFBCAU-BCDBGHSCSA-N 3-Acetyl-11-keto-beta-boswellic acid Chemical compound C1C[C@@H](OC(C)=O)[C@](C)(C(O)=O)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C)CC[C@@H](C)[C@H](C)[C@H]5C4=CC(=O)[C@@H]3[C@]21C HMMGKOVEOFBCAU-BCDBGHSCSA-N 0.000 description 1
- TUYDQQMKXSQIQG-GONBZBRSSA-N 3-[(1e,7e)-8-(2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)-3,6-dioxa-2,7-diazaocta-1,7-dien-1-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC(\C=N\OCCO\N=C\C=2NC(=O)NC(=O)C=2)=C1 TUYDQQMKXSQIQG-GONBZBRSSA-N 0.000 description 1
- HUHDYASLFWQVOL-WZTVWXICSA-N 3-[[2-[[3-[acetyl(methyl)amino]-2,4,6-triiodo-5-(methylcarbamoyl)benzoyl]amino]acetyl]amino]-5-(2-hydroxyethylcarbamoyl)-2,4,6-triiodobenzoic acid;(2r,3r,4r,5s)-6-(methylamino)hexane-1,2,3,4,5-pentol Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CNC(=O)C1=C(I)C(N(C)C(C)=O)=C(I)C(C(=O)NCC(=O)NC=2C(=C(C(=O)NCCO)C(I)=C(C(O)=O)C=2I)I)=C1I HUHDYASLFWQVOL-WZTVWXICSA-N 0.000 description 1
- CTRXDTYTAAKVSM-UHFFFAOYSA-N 3-{[ethyl({4-[(4-{ethyl[(3-sulfophenyl)methyl]amino}phenyl)(2-sulfophenyl)methylidene]cyclohexa-2,5-dien-1-ylidene})azaniumyl]methyl}benzene-1-sulfonate Chemical compound C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C(=CC=CC=2)S(O)(=O)=O)C=CC=1N(CC)CC1=CC=CC(S(O)(=O)=O)=C1 CTRXDTYTAAKVSM-UHFFFAOYSA-N 0.000 description 1
- ZDTNHRWWURISAA-UHFFFAOYSA-N 4',5'-dibromo-3',6'-dihydroxyspiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C(Br)=C1OC1=C(Br)C(O)=CC=C21 ZDTNHRWWURISAA-UHFFFAOYSA-N 0.000 description 1
- RBLUJIWKMSZIMK-UHFFFAOYSA-N 4-n-(4-methoxyphenyl)benzene-1,4-diamine Chemical compound C1=CC(OC)=CC=C1NC1=CC=C(N)C=C1 RBLUJIWKMSZIMK-UHFFFAOYSA-N 0.000 description 1
- WNPVZANXRCPJPW-UHFFFAOYSA-N 5-[isocyano-(4-methylphenyl)sulfonylmethyl]-1,2,3-trimethoxybenzene Chemical compound COC1=C(OC)C(OC)=CC(C([N+]#[C-])S(=O)(=O)C=2C=CC(C)=CC=2)=C1 WNPVZANXRCPJPW-UHFFFAOYSA-N 0.000 description 1
- RYQOILLJDKPETL-UHFFFAOYSA-N 5-aminolevulinic acid hexyl ester Chemical compound CCCCCCOC(=O)CCC(=O)CN RYQOILLJDKPETL-UHFFFAOYSA-N 0.000 description 1
- 229950000258 5-aminolevulinic acid hexyl ester Drugs 0.000 description 1
- HMMGKOVEOFBCAU-UHFFFAOYSA-N AKBA Natural products C1CC(OC(C)=O)C(C)(C(O)=O)C2CCC3(C)C4(C)CCC5(C)CCC(C)C(C)C5C4=CC(=O)C3C21C HMMGKOVEOFBCAU-UHFFFAOYSA-N 0.000 description 1
- 235000009328 Amaranthus caudatus Nutrition 0.000 description 1
- 240000001592 Amaranthus caudatus Species 0.000 description 1
- DHHFDKNIEVKVKS-FMOSSLLZSA-N Betanin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC(C(=C1)O)=CC(C[C@H]2C([O-])=O)=C1[N+]2=C\C=C\1C=C(C(O)=O)N[C@H](C(O)=O)C/1 DHHFDKNIEVKVKS-FMOSSLLZSA-N 0.000 description 1
- DHHFDKNIEVKVKS-MVUYWVKGSA-N Betanin Natural products O=C(O)[C@@H]1NC(C(=O)O)=C/C(=C\C=[N+]/2\[C@@H](C(=O)[O-])Cc3c\2cc(O)c(O[C@H]2[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O2)c3)/C1 DHHFDKNIEVKVKS-MVUYWVKGSA-N 0.000 description 1
- COXVTLYNGOIATD-HVMBLDELSA-N CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O Chemical compound CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O COXVTLYNGOIATD-HVMBLDELSA-N 0.000 description 1
- YSVBPNGJESBVRM-ZPZFBZIMSA-L Carmoisine Chemical compound [Na+].[Na+].C1=CC=C2C(/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)O)=CC=C(S([O-])(=O)=O)C2=C1 YSVBPNGJESBVRM-ZPZFBZIMSA-L 0.000 description 1
- WLYGSPLCNKYESI-RSUQVHIMSA-N Carthamin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1[C@@]1(O)C(O)=C(C(=O)\C=C\C=2C=CC(O)=CC=2)C(=O)C(\C=C\2C([C@](O)([C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C(O)=C(C(=O)\C=C\C=3C=CC(O)=CC=3)C/2=O)=O)=C1O WLYGSPLCNKYESI-RSUQVHIMSA-N 0.000 description 1
- DYQVDISPPLTLLR-HJQYTNQXSA-N Carthamin Natural products CC[C@H]1O[C@H]([C@H](O)[C@@H](O)[C@@H]1O)[C@]2(O)C(=C(C=C/3C(=O)C(=C(O)[C@](O)([C@@H]4O[C@H](CO)[C@@H](O)[C@H](O)[C@H]4O)C3=O)C(=O)C=Cc5ccc(O)cc5)C(=O)C(=C2O)C(=O)C=Cc6ccc(O)cc6)O DYQVDISPPLTLLR-HJQYTNQXSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 101710082261 Competence-stimulating peptide Proteins 0.000 description 1
- 235000005956 Cosmos caudatus Nutrition 0.000 description 1
- 241000219104 Cucurbitaceae Species 0.000 description 1
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 1
- 241001519550 Delisea Species 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010013911 Dysgeusia Diseases 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000005744 Glycoside Hydrolases Human genes 0.000 description 1
- 108010031186 Glycoside Hydrolases Proteins 0.000 description 1
- 240000005979 Hordeum vulgare Species 0.000 description 1
- 235000007340 Hordeum vulgare Nutrition 0.000 description 1
- 206010021036 Hyponatraemia Diseases 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- 240000005561 Musa balbisiana Species 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- 229940123361 Quorum sensing inhibitor Drugs 0.000 description 1
- 239000004228 Riboflavin-5'-Phosphate Substances 0.000 description 1
- ZJUKTBDSGOFHSH-WFMPWKQPSA-N S-Adenosylhomocysteine Chemical compound O[C@@H]1[C@H](O)[C@@H](CSCC[C@H](N)C(O)=O)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZJUKTBDSGOFHSH-WFMPWKQPSA-N 0.000 description 1
- MEFKEPWMEQBLKI-AIRLBKTGSA-N S-adenosyl-L-methioninate Chemical compound O[C@@H]1[C@H](O)[C@@H](C[S+](CC[C@H](N)C([O-])=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MEFKEPWMEQBLKI-AIRLBKTGSA-N 0.000 description 1
- 235000006580 Salvadora persica Nutrition 0.000 description 1
- 240000007542 Salvadora persica Species 0.000 description 1
- 102400000830 Saposin-B Human genes 0.000 description 1
- 101800001697 Saposin-B Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- FOIXSVOLVBLSDH-UHFFFAOYSA-N Silver ion Chemical compound [Ag+] FOIXSVOLVBLSDH-UHFFFAOYSA-N 0.000 description 1
- FHNINJWBTRXEBC-UHFFFAOYSA-N Sudan III Chemical compound OC1=CC=C2C=CC=CC2=C1N=NC(C=C1)=CC=C1N=NC1=CC=CC=C1 FHNINJWBTRXEBC-UHFFFAOYSA-N 0.000 description 1
- 240000001717 Vaccinium macrocarpon Species 0.000 description 1
- 235000012545 Vaccinium macrocarpon Nutrition 0.000 description 1
- 235000002118 Vaccinium oxycoccus Nutrition 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 229960004308 acetylcysteine Drugs 0.000 description 1
- CQPFMGBJSMSXLP-UHFFFAOYSA-M acid orange 7 Chemical compound [Na+].OC1=CC=C2C=CC=CC2=C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 CQPFMGBJSMSXLP-UHFFFAOYSA-M 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 229960001570 ademetionine Drugs 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 235000012735 amaranth Nutrition 0.000 description 1
- 239000004178 amaranth Substances 0.000 description 1
- 229950004388 anazolene sodium Drugs 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 235000010208 anthocyanin Nutrition 0.000 description 1
- 239000004410 anthocyanin Substances 0.000 description 1
- 229930002877 anthocyanin Natural products 0.000 description 1
- 150000004636 anthocyanins Chemical class 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 229940027989 antiseptic and disinfectant iodine product Drugs 0.000 description 1
- 125000003289 ascorbyl group Chemical group [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 description 1
- WXLFIFHRGFOVCD-UHFFFAOYSA-L azophloxine Chemical compound [Na+].[Na+].OC1=C2C(NC(=O)C)=CC(S([O-])(=O)=O)=CC2=CC(S([O-])(=O)=O)=C1N=NC1=CC=CC=C1 WXLFIFHRGFOVCD-UHFFFAOYSA-L 0.000 description 1
- 239000004176 azorubin Substances 0.000 description 1
- TVWOWDDBXAFQDG-DQRAZIAOSA-N azorubine Chemical compound C1=CC=C2C(\N=N/C3=C(C4=CC=CC=C4C(=C3)S(O)(=O)=O)O)=CC=C(S(O)(=O)=O)C2=C1 TVWOWDDBXAFQDG-DQRAZIAOSA-N 0.000 description 1
- 235000013405 beer Nutrition 0.000 description 1
- 235000002185 betanin Nutrition 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000009530 blood pressure measurement Methods 0.000 description 1
- 235000012670 brown HT Nutrition 0.000 description 1
- 239000001678 brown HT Substances 0.000 description 1
- ADGGJQPKBDIZMT-IAXIIBAVSA-K c12c(O)cc(S(=O)(=O)O[Na])cc2cc(S(=O)(=O)O[Na])cc1\N=N\c(c1c2c(ccc1)S(=O)(=O)O[Na])ccc2Nc1ccccc1 Chemical compound c12c(O)cc(S(=O)(=O)O[Na])cc2cc(S(=O)(=O)O[Na])cc1\N=N\c(c1c2c(ccc1)S(=O)(=O)O[Na])ccc2Nc1ccccc1 ADGGJQPKBDIZMT-IAXIIBAVSA-K 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 235000012682 canthaxanthin Nutrition 0.000 description 1
- FDSDTBUPSURDBL-DKLMTRRASA-N canthaxanthin Chemical compound CC=1C(=O)CCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)C(=O)CCC1(C)C FDSDTBUPSURDBL-DKLMTRRASA-N 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 229940114118 carminic acid Drugs 0.000 description 1
- DGQLVPJVXFOQEV-NGOCYOHBSA-N carminic acid Chemical compound OC1=C2C(=O)C=3C(C)=C(C(O)=O)C(O)=CC=3C(=O)C2=C(O)C(O)=C1[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O DGQLVPJVXFOQEV-NGOCYOHBSA-N 0.000 description 1
- 229940031019 carmoisine Drugs 0.000 description 1
- 150000001746 carotenes Chemical class 0.000 description 1
- 235000005473 carotenes Nutrition 0.000 description 1
- 102000014509 cathelicidin Human genes 0.000 description 1
- 108060001132 cathelicidin Proteins 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- AIOLRLMFOWGSPL-UHFFFAOYSA-N chembl1337820 Chemical compound C1=CC=C2C(N=NC3=C4C=CC(=CC4=CC(=C3O)S(O)(=O)=O)S(O)(=O)=O)=CC=CC2=C1 AIOLRLMFOWGSPL-UHFFFAOYSA-N 0.000 description 1
- PZTQVMXMKVTIRC-UHFFFAOYSA-L chembl2028348 Chemical compound [Ca+2].[O-]S(=O)(=O)C1=CC(C)=CC=C1N=NC1=C(O)C(C([O-])=O)=CC2=CC=CC=C12 PZTQVMXMKVTIRC-UHFFFAOYSA-L 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000001752 chlorophylls and chlorophyllins Substances 0.000 description 1
- 235000012698 chlorophylls and chlorophyllins Nutrition 0.000 description 1
- 235000013986 citrus red 2 Nutrition 0.000 description 1
- 239000001679 citrus red 2 Substances 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 229940080423 cochineal Drugs 0.000 description 1
- JZGWEIPJUAIDHM-QURGRASLSA-N cochineal red a Chemical compound C1=CC=C2C(/N=N/C3=C4C(=CC(=CC4=CC=C3O)S(O)(=O)=O)S(O)(=O)=O)=CC=C(S(O)(=O)=O)C2=C1 JZGWEIPJUAIDHM-QURGRASLSA-N 0.000 description 1
- 239000000571 coke Substances 0.000 description 1
- 229940079356 contact laxatives Drugs 0.000 description 1
- 239000004121 copper complexes of chlorophylls and chlorophyllins Substances 0.000 description 1
- 235000012700 copper complexes of chlorophylls and chlorophyllins Nutrition 0.000 description 1
- 235000012495 crackers Nutrition 0.000 description 1
- 235000004634 cranberry Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229960005223 diatrizoic acid Drugs 0.000 description 1
- 235000013325 dietary fiber Nutrition 0.000 description 1
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
- 229940008099 dimethicone Drugs 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- VPWFPZBFBFHIIL-UHFFFAOYSA-L disodium 4-[(4-methyl-2-sulfophenyl)diazenyl]-3-oxidonaphthalene-2-carboxylate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)C1=CC(C)=CC=C1N=NC1=C(O)C(C([O-])=O)=CC2=CC=CC=C12 VPWFPZBFBFHIIL-UHFFFAOYSA-L 0.000 description 1
- WZRZTHMJPHPAMU-UHFFFAOYSA-L disodium;(3e)-3-[(4-amino-3-sulfonatophenyl)-(4-amino-3-sulfophenyl)methylidene]-6-imino-5-methylcyclohexa-1,4-diene-1-sulfonate Chemical compound [Na+].[Na+].C1=C(S([O-])(=O)=O)C(=N)C(C)=CC1=C(C=1C=C(C(N)=CC=1)S([O-])(=O)=O)C1=CC=C(N)C(S(O)(=O)=O)=C1 WZRZTHMJPHPAMU-UHFFFAOYSA-L 0.000 description 1
- AHSJNHONMVUMLK-UHFFFAOYSA-L disodium;4',5'-diiodo-3-oxospiro[2-benzofuran-1,9'-xanthene]-3',6'-diolate Chemical compound [Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC=C([O-])C(I)=C1OC1=C(I)C([O-])=CC=C21 AHSJNHONMVUMLK-UHFFFAOYSA-L 0.000 description 1
- TUQJHVRCALPCHU-QPRXZMCZSA-L disodium;4-[(2z)-2-[(5e)-3-(hydroxymethyl)-4,6-dioxo-5-[(4-sulfonatonaphthalen-1-yl)hydrazinylidene]cyclohex-2-en-1-ylidene]hydrazinyl]naphthalene-1-sulfonate Chemical compound [Na+].[Na+].C1=CC=C2C(N/N=C3/C(=O)C(=N\NC=4C5=CC=CC=C5C(=CC=4)S([O-])(=O)=O)/C=C(C3=O)CO)=CC=C(S([O-])(=O)=O)C2=C1 TUQJHVRCALPCHU-QPRXZMCZSA-L 0.000 description 1
- FPAYXBWMYIMERV-UHFFFAOYSA-L disodium;5-methyl-2-[[4-(4-methyl-2-sulfonatoanilino)-9,10-dioxoanthracen-1-yl]amino]benzenesulfonate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)C1=CC(C)=CC=C1NC(C=1C(=O)C2=CC=CC=C2C(=O)C=11)=CC=C1NC1=CC=C(C)C=C1S([O-])(=O)=O FPAYXBWMYIMERV-UHFFFAOYSA-L 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229960001483 eosin Drugs 0.000 description 1
- IINNWAYUJNWZRM-UHFFFAOYSA-L erythrosin B Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=C(I)C([O-])=C(I)C=C21 IINNWAYUJNWZRM-UHFFFAOYSA-L 0.000 description 1
- 235000012732 erythrosine Nutrition 0.000 description 1
- 239000004174 erythrosine Substances 0.000 description 1
- 229940011411 erythrosine Drugs 0.000 description 1
- 229960003699 evans blue Drugs 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- FCQJEPASRCXVCB-UHFFFAOYSA-N flavianic acid Chemical compound C1=C(S(O)(=O)=O)C=C2C(O)=C([N+]([O-])=O)C=C([N+]([O-])=O)C2=C1 FCQJEPASRCXVCB-UHFFFAOYSA-N 0.000 description 1
- FVTCRASFADXXNN-SCRDCRAPSA-N flavin mononucleotide Chemical compound OP(=O)(O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O FVTCRASFADXXNN-SCRDCRAPSA-N 0.000 description 1
- 239000011768 flavin mononucleotide Substances 0.000 description 1
- 229940084343 fleet phospho-soda Drugs 0.000 description 1
- 238000009541 flexible sigmoidoscopy Methods 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 150000002241 furanones Chemical class 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 235000009569 green tea Nutrition 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- LZYXPFZBAZTOCH-UHFFFAOYSA-N hexyl 5-amino-4-oxopentanoate;hydron;chloride Chemical compound Cl.CCCCCCOC(=O)CCC(=O)CN LZYXPFZBAZTOCH-UHFFFAOYSA-N 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- UHOKSCJSTAHBSO-UHFFFAOYSA-N indanthrone blue Chemical compound C1=CC=C2C(=O)C3=CC=C4NC5=C6C(=O)C7=CC=CC=C7C(=O)C6=CC=C5NC4=C3C(=O)C2=C1 UHOKSCJSTAHBSO-UHFFFAOYSA-N 0.000 description 1
- 229960003988 indigo carmine Drugs 0.000 description 1
- KHLVKKOJDHCJMG-QDBORUFSSA-L indigo carmine Chemical compound [Na+].[Na+].N/1C2=CC=C(S([O-])(=O)=O)C=C2C(=O)C\1=C1/NC2=CC=C(S(=O)(=O)[O-])C=C2C1=O KHLVKKOJDHCJMG-QDBORUFSSA-L 0.000 description 1
- 229960004657 indocyanine green Drugs 0.000 description 1
- MOFVSTNWEDAEEK-UHFFFAOYSA-M indocyanine green Chemical compound [Na+].[O-]S(=O)(=O)CCCCN1C2=CC=C3C=CC=CC3=C2C(C)(C)C1=CC=CC=CC=CC1=[N+](CCCCS([O-])(=O)=O)C2=CC=C(C=CC=C3)C3=C2C1(C)C MOFVSTNWEDAEEK-UHFFFAOYSA-M 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 229960004359 iodixanol Drugs 0.000 description 1
- 229960001025 iohexol Drugs 0.000 description 1
- 229960004647 iopamidol Drugs 0.000 description 1
- DGAIEPBNLOQYER-UHFFFAOYSA-N iopromide Chemical compound COCC(=O)NC1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)N(C)CC(O)CO)=C1I DGAIEPBNLOQYER-UHFFFAOYSA-N 0.000 description 1
- 229960002611 ioxilan Drugs 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 235000010213 iron oxides and hydroxides Nutrition 0.000 description 1
- 239000004407 iron oxides and hydroxides Substances 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229940125722 laxative agent Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 235000012680 lutein Nutrition 0.000 description 1
- 239000001656 lutein Substances 0.000 description 1
- KBPHJBAIARWVSC-RGZFRNHPSA-N lutein Chemical compound C([C@H](O)CC=1C)C(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\[C@H]1C(C)=C[C@H](O)CC1(C)C KBPHJBAIARWVSC-RGZFRNHPSA-N 0.000 description 1
- 229960005375 lutein Drugs 0.000 description 1
- ORAKUVXRZWMARG-WZLJTJAWSA-N lutein Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=CC(O)CC2(C)C)C ORAKUVXRZWMARG-WZLJTJAWSA-N 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- MIKKOBKEXMRYFQ-WZTVWXICSA-N meglumine amidotrizoate Chemical compound C[NH2+]C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CC(=O)NC1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I MIKKOBKEXMRYFQ-WZTVWXICSA-N 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- MCPLVIGCWWTHFH-UHFFFAOYSA-L methyl blue Chemical compound [Na+].[Na+].C1=CC(S(=O)(=O)[O-])=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[NH+]C=2C=CC(=CC=2)S([O-])(=O)=O)C=2C=CC(NC=3C=CC(=CC=3)S([O-])(=O)=O)=CC=2)C=C1 MCPLVIGCWWTHFH-UHFFFAOYSA-L 0.000 description 1
- 229960004712 metrizoic acid Drugs 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 235000015205 orange juice Nutrition 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000002357 osmotic agent Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 210000003254 palate Anatomy 0.000 description 1
- 235000012736 patent blue V Nutrition 0.000 description 1
- YCOFRPYSZKIPBQ-UHFFFAOYSA-N penicillic acid Natural products COC1=CC(=O)OC1(O)C(C)=C YCOFRPYSZKIPBQ-UHFFFAOYSA-N 0.000 description 1
- VOUGEZYPVGAPBB-UHFFFAOYSA-N penicillin acid Natural products OC(=O)C=C(OC)C(=O)C(C)=C VOUGEZYPVGAPBB-UHFFFAOYSA-N 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- GVKCHTBDSMQENH-UHFFFAOYSA-L phloxine B Chemical compound [Na+].[Na+].[O-]C(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 GVKCHTBDSMQENH-UHFFFAOYSA-L 0.000 description 1
- ZYIBVBKZZZDFOY-UHFFFAOYSA-N phloxine O Chemical compound O1C(=O)C(C(=C(Cl)C(Cl)=C2Cl)Cl)=C2C21C1=CC(Br)=C(O)C(Br)=C1OC1=C(Br)C(O)=C(Br)C=C21 ZYIBVBKZZZDFOY-UHFFFAOYSA-N 0.000 description 1
- 235000012703 plain caramel Nutrition 0.000 description 1
- 239000004122 plain caramel Substances 0.000 description 1
- 108010004131 poly(beta-D-mannuronate) lyase Proteins 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- 239000006041 probiotic Substances 0.000 description 1
- 235000018291 probiotics Nutrition 0.000 description 1
- 239000002325 prokinetic agent Substances 0.000 description 1
- 230000001543 purgative effect Effects 0.000 description 1
- 235000012752 quinoline yellow Nutrition 0.000 description 1
- 239000004172 quinoline yellow Substances 0.000 description 1
- 229940051201 quinoline yellow Drugs 0.000 description 1
- IZMJMCDDWKSTTK-UHFFFAOYSA-N quinoline yellow Chemical compound C1=CC=CC2=NC(C3C(C4=CC=CC=C4C3=O)=O)=CC=C21 IZMJMCDDWKSTTK-UHFFFAOYSA-N 0.000 description 1
- 235000012739 red 2G Nutrition 0.000 description 1
- 239000004180 red 2G Substances 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 229940043267 rhodamine b Drugs 0.000 description 1
- 235000019192 riboflavin Nutrition 0.000 description 1
- 239000002151 riboflavin Substances 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- 235000019231 riboflavin-5'-phosphate Nutrition 0.000 description 1
- 229920002477 rna polymer Polymers 0.000 description 1
- 235000019643 salty taste Nutrition 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229950008974 sinefungin Drugs 0.000 description 1
- VVNRQZDDMYBBJY-UHFFFAOYSA-M sodium 1-[(1-sulfonaphthalen-2-yl)diazenyl]naphthalen-2-olate Chemical compound [Na+].C1=CC=CC2=C(S([O-])(=O)=O)C(N=NC3=C4C=CC=CC4=CC=C3O)=CC=C21 VVNRQZDDMYBBJY-UHFFFAOYSA-M 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229960001790 sodium citrate Drugs 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- GOZDTZWAMGHLDY-UHFFFAOYSA-L sodium picosulfate Chemical compound [Na+].[Na+].C1=CC(OS(=O)(=O)[O-])=CC=C1C(C=1N=CC=CC=1)C1=CC=C(OS([O-])(=O)=O)C=C1 GOZDTZWAMGHLDY-UHFFFAOYSA-L 0.000 description 1
- NLUFDZBOHMOBOE-UHFFFAOYSA-M sodium;2-[[4-(diethylamino)phenyl]-(4-diethylazaniumylidenecyclohexa-2,5-dien-1-ylidene)methyl]benzene-1,4-disulfonate Chemical compound [Na+].C1=CC(N(CC)CC)=CC=C1C(C=1C(=CC=C(C=1)S([O-])(=O)=O)S([O-])(=O)=O)=C1C=CC(=[N+](CC)CC)C=C1 NLUFDZBOHMOBOE-UHFFFAOYSA-M 0.000 description 1
- LJFWQNJLLOFIJK-UHFFFAOYSA-N solvent violet 13 Chemical compound C1=CC(C)=CC=C1NC1=CC=C(O)C2=C1C(=O)C1=CC=CC=C1C2=O LJFWQNJLLOFIJK-UHFFFAOYSA-N 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- YCUVUDODLRLVIC-VPHDGDOJSA-N sudan black b Chemical compound C1=CC(=C23)NC(C)(C)NC2=CC=CC3=C1\N=N\C(C1=CC=CC=C11)=CC=C1\N=N\C1=CC=CC=C1 YCUVUDODLRLVIC-VPHDGDOJSA-N 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000012756 tartrazine Nutrition 0.000 description 1
- 239000004149 tartrazine Substances 0.000 description 1
- 229960000943 tartrazine Drugs 0.000 description 1
- UJMBCXLDXJUMFB-GLCFPVLVSA-K tartrazine Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)C1=NN(C=2C=CC(=CC=2)S([O-])(=O)=O)C(=O)C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 UJMBCXLDXJUMFB-GLCFPVLVSA-K 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 235000010215 titanium dioxide Nutrition 0.000 description 1
- 229960001555 tolonium chloride Drugs 0.000 description 1
- HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 description 1
- KBPHJBAIARWVSC-XQIHNALSSA-N trans-lutein Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C(=CC(O)CC2(C)C)C KBPHJBAIARWVSC-XQIHNALSSA-N 0.000 description 1
- SWGJCIMEBVHMTA-UHFFFAOYSA-K trisodium;6-oxido-4-sulfo-5-[(4-sulfonatonaphthalen-1-yl)diazenyl]naphthalene-2-sulfonate Chemical compound [Na+].[Na+].[Na+].C1=CC=C2C(N=NC3=C4C(=CC(=CC4=CC=C3O)S([O-])(=O)=O)S([O-])(=O)=O)=CC=C(S([O-])(=O)=O)C2=C1 SWGJCIMEBVHMTA-UHFFFAOYSA-K 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 235000012712 vegetable carbon Nutrition 0.000 description 1
- 239000004108 vegetable carbon Substances 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 238000003466 welding Methods 0.000 description 1
- FJHBOVDFOQMZRV-XQIHNALSSA-N xanthophyll Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C=C(C)C(O)CC2(C)C FJHBOVDFOQMZRV-XQIHNALSSA-N 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/765—Polymers containing oxygen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/04—Sulfur, selenium or tellurium; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/10—Laxatives
Abstract
The invention provides a method of cleansing the colon of a subject before a diagnostic, therapeutic or surgical procedure 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 first colon cleansing solution comprises 70 to 250 g per litre PEG and 2.0 to 20 g per litre of one or more alkali metal sulphates, alkaline earth metal sulphates, or a mixture thereof. The second colon cleansing solution comprises 300 to 800 mmol per litre ascorbate anion provided by a mixture of ascorbic acid and one or more salts of ascorbic acid in a ratio from 1:4.5 to 1:7, and 10 to 200 g per litre polyethylene glycol. 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 t2 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).
Description
METHOD OF CLEANSING THE COLON
The present invention relates to a method of cleansing the colon using colon cleansing solutions, and
compositions and kits associated therewith. Colon cleansing compositions are also known as lavage
solutions, bowel cleansers, purgatives or colonic évacuants.
1. Background
Colon or bowel cleansing is important before numerous surgical or diagnostic procedures, including
colonoscopy, barium enema examination, sigmoidoscopy and colon surgery. Such procedures are
often carried out on an outpatient basis and thus it is desirable that the colon cleansing be carried out
by the patient at home, prior to arrival at the hospital or surgery where the procedure is to take place.
It is therefore important that patient compliance is good without medical supervision if satisfactory
colon cleansing is to be achieved prior to the procedure.
Intestinal lavage, in which a large volume of an aqueous electrolyte solution containing sodium
sulphate and polyethylene glycol is ingested, is one of the most common methods for colon cleansing.
These osmotically active agents are non-absorbable or only poorly absorbable and thus retain water in
the bowel, resulting in copious diarrhoea and cleansing of the colon.
For effective cleansing, many of these compositions must be ingested in quantities of between 2 to 4
litres. The unpleasant taste of these compositions combined with the large volumes required to be
ingested often contributes to nausea or vomiting, resulting in poor patient compliance and failure to
consume the full volume of solution. Poor patient compliance can lead to inadequate preparation of
the colon which can, in turn, lead to cancellation or repetition of the colonoscopy or other procedure
becoming necessary or, worse, non-detection of lesions or polyps indicative of cancer risk. Detection
of polyps in the right-sided colon is particularly challenging (see for example Qumseya et al. Clinical
and Translational Gastroenterology, 2012, doi: 10.1038/ctg.2012.14).
A number of improved colon cleansing compositions are described in . A colon
cleansing composition according to that comprises polyethylene glycol 3350,
sodium sulphate, an ascorbate component, electrolytes, sweetener and flavouring is commercialised as
a powder for oral solution under the tradename MOVIPREP® (registered trademark of Velinor AG, a
member of the Norgine group of companies). The MOVIPREP solution is effective despite being
taken in a substantially lower volume than other colon cleansing solutions. Typically, only 2 litres of
the solution need to be taken by an adult patient (along with additional clear fluid), a significant
benefit when compared to taking 4 litres of previous solutions.
A recent advance in colon cleansing agents is provided by the product marketed as SUPREP by
Braintree Laboratories, Inc. SUPRPEP contains 17.5g sodium sulphate, 3.13g potassium sulphate and
1.6g magnesium sulphate and it is taken in a volume of 16 US fluid ounces (473ml). A treatment
comprises two doses of that solution.
Various regimens for the timing of ingestion of colon cleansing solutions are mentioned in the
literature and in patient information leaflets that accompany colon cleansing products. For example,
the MOVIPREP solution mentioned above may be taken (optionally with additional clear liquids also
being taken) in the evening before the examination or procedure, or the MOVIPREP solution may be
taken in a “split-dose” regimen, with approximately half of the cleansing solution being taken the
evening before the examination or procedure (“first dose”), and the remainder being taken the
following morning (“second dose”). Similarly, the SUPREP product mentioned above is
recommended to be taken as first dose in the evening before the examination procedure, accompanied
by an additional quart of water (946ml), followed by a second dose in the morning of the procedure.
An alternative to the lavage solutions described above is provided by low volume hypertonic salt
solutions. Examples include Fleet’s phosphosoda product and sodium picosulphate solutions. These
are very concentrated salt solutions and patients need ingest only a small volume of them (around
100ml). However, these products have been associated with a hypo-osmolar state and electrolyte
imbalance in subjects, particularly hyponatremia. They are particularly contra-indicated in subjects
with kidney problems.
Despite the advances that have been made, all lavage-type colon cleansing products on the market
continue to require a subject to ingest a large volume of solution (2 litres in the case of the
MOVIPREP solution). Many subjects find the ingestion of a large volume unpleasant or difficult and
poor patient compliance thus remains a problem. There remains a need for alternative colon cleansing
solutions that are effective when ingested in small volumes, but do not cause electrolyte imbalances in
subjects. There also remains a need for colon cleansing solutions that are more pleasant for subjects
to ingest, whilst retaining good cleansing effectiveness. It is an object of the present invention to meet
this need, or at least go some way to provide the public with a useful choice.
2. Summary of the invention
The invention provides, in a first aspect, 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.
This is sometimes referred hereafter as “solution of the invention”.
The solution of the invention has a surprisingly palatable taste. The particular ratio of ascorbic acid to
salt of ascorbic acid enables the salty taste of ascorbate salt to be balanced by sourness from acid to a
palatable extent, whilst at the same time not reducing the osmotic effect of the ascorbate component
or making the solution too sour. The solution of the invention is highly effective as a colon cleansing
solution when ingested in a lower volume than many prior art solutions, and it has a good tolerability
profile.
In a particular aspect, the present invention provides a use of a first colon cleansing solution
comprising:
(i) 70 to 250 g per litre polyethylene glycol having an average molecular weight of 2500 to
4500 Da.,
(ii) 2.0 to 20 g per litre of one or more alkali metal sulphates, alkaline earth metal sulphates
or a mixture thereof,
(iii) optionally one or more electrolytes,
(iv) optionally one or more flavouring agents, and
(v) optionally one or more sweeteners; and
a 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;
in the manufacture of a medicament for cleansing the colon of a subject before a diagnostic,
therapeutic or surgical procedure;
wherein the colon of the subject is to be cleansed by a method 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,
whereby the first colon cleansing solution is taken over a time period t(d1) followed by
optional additional water based beverage over a time period t(cf1), and then following a time
[FOLLOWED BY PAGE 3A]
interval t(dose interval), the second colon cleansing solution is taken over a time period t(d2)
followed by optional additional water based beverage over a time period t(cf2), whereby the
subject undergoes the surgical, therapeutic or diagnostic procedure at a time t2 after the
beginning of the colon cleansing method, and whereby the time interval after the completion
of the second additional water based beverage and the start of the surgical, therapeutic or
diagnostic procedure is t(procedure interval);
and wherein:
(i) t is in the range of from 10 to 36 hours;
t(dose interval) is in the range of from 0 to 8 hours; and
t(procedure interval) is in the range from 8 to 20 hours; or
(ii) t is in the range of from 10 to 36 hours;
t(dose interval) is in the range of from 8 to 20 hours; and
t(procedure interval) is in the range from 30 minutes to 10 hours; or
(iii) t is in the range of from 3 to 14 hours;
t(dose interval) is in the range of from 0 minutes to 8 hours; and
t(procedure interval) is in the range from 30 minutes to 10 hours.
In this specification where reference has been made to patent specifications, other external documents,
or other sources of information, this is generally for the purpose of providing a context for discussing
the features of the invention. Unless specifically stated otherwise, reference to such external
documents is not to be construed as an admission that such documents, or such sources of
information, in any jurisdiction, are prior art, or form part of the common general knowledge in the
In the description in this specification reference may be made to subject matter which is not within the
scope of the appended claims. That subject matter should be readily identifiable by a person skilled in
the art and may assist in putting into practice the invention as defined in the appended claims.
3. Detailed description
a) Contents of solutions
The solutions of the invention are aqueous solutions. The mixture of ascorbic acid and one or more
salts of ascorbic acid will, for convenience, be referred to herein as the “ascorbate component”.
Suitable salts of ascorbic acid include alkali metal salts and alkaline earth metal salts. For example, a
salt may be selected from sodium, potassium, magnesium and calcium salts. For example, preferred
salts of ascorbic acid include sodium ascorbate, potassium ascorbate, magnesium ascorbate and
[FOLLOWED BY PAGE 3B]
calcium ascorbate. The molar ratio between (i) the ascorbic acid and (ii) the one or more salts of
ascorbic acid is the molar ratio of the ascorbate moieties; for example, magnesium ascorbate
comprises two moles of ascorbate per mole of salt; for the ratio purposes, it is the number of moles of
ascorbate that is counted. Particularly preferred salts of ascorbic acid are magnesium ascorbate and
sodium ascorbate, for example sodium ascorbate. In one embodiment, the solution of the invention
comprises ascorbic acid and sodium ascorbate (and preferably no further ascorbate).
Preferably, the molar ratio of the components (i) and (ii) is from 1:4.75 to 1:6.75; more preferably
from 1:5.0 to 1:6.0; for example from 1:5.40 to 1:5.80; for example 15:85.
The solution of the invention preferably comprises ascorbate anion in a concentration of: 300-
700mmol per litre, for example 350-650mmol per litre, for example 450-600 mmol per litre.
A solution of the invention may comprise 50 to 140g/litre of ascorbate component. For example, a
solution of the invention comprises 60 to 140g/litre, for example 80 to 130g/litre, for example 80 to
120g/litre, for example 100 to 120g/litre of ascorbate component.
Ascorbic acid has a molecular weight of 176g/mol. Sodium ascorbate has a molecular weight of
198g/mol. Accordingly, a mixture of ascorbic acid and sodium ascorbate in a molar ratio of from
1:4.5 to 1:7.0 has ascorbic acid and sodium ascorbate present in a weight ratio of 1:5.063 to 1:7.875.
For example, the weight ratio can be 1:5.344 to 1:7.594; more preferably from 1:5.625 to 1:6.75; for
example from 1:6.075 to 1:6.525, for example 1:6.38. For example, a solution of the invention may
comprise from 6 to 25 g/litre of ascorbic acid and 50 to 120 g/litre of sodium ascorbate, for example
12 to 20 g/litre of ascorbic acid and 80 to 120 g/litre of sodium ascorbate (with the ratio between them
[FOLLOWED BY PAGE 4]
being as mentioned above). For example, a solution of the invention may comprise from 14 to 16g
g/litre of ascorbic acid and 92 to 100 g/litre of sodium ascorbate.
Potassium ascorbate has a molecular weight of 214g/mol. Accordingly, a mixture of ascorbic acid
and potassium ascorbate in a molar ratio of from 1:4.5 to 1:7.0 has ascorbic acid and potassium
ascorbate present in a weight ratio of 1:5.471 to 1:8.511. For example, the weight ratio can be 1:5.776
to 1:8.208; more preferably from 1:6.080 to 1:7.295; for example from 1:6.565 to 1:7.052, for
example 1:6.896. For example, a solution of the invention may comprise from 6 to 25 g/litre of
ascorbic acid and 50 to 125 g/litre of potassium ascorbate, for example 6 to 12 g/litre of ascorbic acid
and 80 to 120 g/litre of potassium ascorbate.
Magnesium ascorbate has a molecular weight of 374.5g/mol and each mole of magnesium ascorbate
provides two moles of ascorbate. Accordingly, a mixture of ascorbic acid and magnesium ascorbate
in a molar ratio of from 1:4.5 to 1:7.0 (of ascorbate anion) has ascorbic acid and magnesium ascorbate
present in a weight ratio of 1:4.794 to 1:7.457. For example, the weight ratio can be 1:5.061 to
1:7.191; more preferably from 1:5.326 to 1:6.397 for example from 1:5.753 to 1:6.179, for example
1:6.042. For example, a solution of the invention may comprise from 6 to 25 g/litre of ascorbic acid
and 45 to 120 g/litre of magnesium ascorbate, for example 6 to 12 g/litre of ascorbic acid and 75 to
115 g/litre of magnesium ascorbate.
Depending on the pH of the solution of the invention, some ascorbate anion may be protonated and
thus exist as free ascorbic acid in solution. At the pH of solutions that would typically be
administered, only a very minor proportion of ascorbate is protonated. In calculations of
concentrations of "ascorbate anion" herein, the concentration of "ascorbate anion" is taken as the total
concentration of all ascorbate anion present, including the proportion that is protonated.
The cleansing solution comprises polyethylene glycol. The polyethylene glycol (PEG) may, for
example, have an average molecular weight of 2000 to 8000, for example 2500 to 4500 Da, for
example 2680 to 4020 Da, for example 3000 to 4000 Da. For example, the PEG may be PEG 3350 or
PEG 4000 as defined in national pharmacopeias. PEG8000 may also be used. Further examples of
suitable PEGs recognized in some national pharmacopeias include Macrogols, for example Macrogol
3350 or Macrogol 4000.
The cleansing solution comprises 10 to 200 g per litre of PEG. Preferably, the solution of the
invention comprises 20 to 160g per litre of PEG, more preferably 40 to 120 g per litre, for example 60
to 100 g per litre, for example 75 to 85 g per litre, for example 80 g per litre.
The cleansing solution may additionally comprise one or more of:
c) one or more electrolytes;
d) one or more alkali metal or alkaline earth metal sulphates;
e) one or more flavouring agents;
f) one or more sweeteners.
The cleansing solution may comprise one or more electrolytes. Electrolytes include salts of sodium,
potassium, calcium and magnesium, particularly sodium and potassium; and salts of chloride, iodide,
bicarbonate and carbonate, particularly chloride. Preferred electrolytes are sodium chloride and
potassium chloride. In an embodiment, the solution is essentially free from sodium bicarbonate, for
example essentially free from any bicarbonate.
For example, the solution of the invention may comprise sodium chloride at a concentration of 1 to 10
g per litre. For example, sodium chloride may be present at a concentration of 3 to 8 g per litre, for
example 4 to 7g per litre; for example 6.0 to 6.8g per litre; for example 5.6g per litre or 6.4g per litre.
For example, the solution of the invention may comprise potassium chloride at a concentration of 1 to
g per litre. For example, potassium chloride may be present at a concentration of 1 to 7 g per litre,
for example 1.5 to 5g per litre, for example 1.5 to 3g per litre, for example 2.0 to 2.8 g per litre; for
example 2.4g per litre or 2.6g per litre.
In an embodiment, the solution of the invention comprises sodium chloride and potassium chloride.
They can be present in the amounts mentioned immediately above. For example, sodium chloride
may be present at a concentration of 4 to 7g per litre and potassium chloride may be present at a
concentration of 1.5 to 3g per litre.
The cleansing solution may comprise one or more alkali metal sulphates, alkaline earth metal
sulphates or a mixture thereof (herein referred to as a "sulphate component"). An alkali metal or
alkaline earth metal sulphate may, for example, be selected from sodium sulphate, potassium sulphate
and magnesium sulphate. The solution of the invention may comprise more than one of sodium
sulphate, potassium sulphate and magnesium sulphate, for example all three. Preferably, the sulphate
component is or includes sodium sulphate.
For example, the solution of the invention may comprise a sulphate component at a concentration of 2
to 20 g per litre, for example 5 to 15 g per litre, for example 8 to 15 g per litre, for example 10 to 14 g
per litre, for example 12 g per litre. The one or more sulphate salts may be provided in any
pharmaceutically acceptable form: they may each be anhydrous, or be in a hydrated form. The
weights mentioned herein refer to the weight of the sulphate salt excluding any water of hydration.
In an alternative preferred embodiment, the solution of the invention does not comprise a sulphate
component; that is to say that the solution is essentially free from alkali metal sulphates and alkaline
earth metal sulphates; in particular essentially free from sodium sulphate, potassium sulphate and
magnesium sulphate.
Herein, the term "essentially free from" a component means that the named component is present at a
level that is below the level that has any functional effect in the solution of the invention in its use; for
example, the named component may be at a level that is below the level at which it has a measurable
clinical effect. For example, it may mean that the component is present at a level of less than 0. Ig per
litre; for example less than 0.03g per litre; for example less than 0.01g per litre, for example less than
0.003g per litre, for example less than 0.001g per litre.
In the solutions of the invention described herein, the quantities of the individual components recited
do not include any solutes that may be present in the water used to prepare the solutions, for example,
in hard water areas there may be significant amounts of Ca2+ and Mg2+ carbonates, bicarbonates or
sulphates present in tap water.
The cleansing solution preferably includes a flavouring agent. A flavouring agent for use in
compositions of the invention should preferably mask saltiness, be relatively sweet but not
excessively so, and be stable in the composition. A flavouring agent makes the solutions more
palatable and thus aids patient compliance. Preferred flavourings include lemon e.g. Ungerer Lemon
(available from Ungerer Limited, Sealand Road, Chester, England CHI 4LP), strawberry e.g. Ungerer
Strawberry, grapefruit e.g. Ungerer Grapefruit flavouring powder, blackcurrant e.g. Ungerer
Blackcurrant, pineapple e.g. IFF (International Flavours and Fragrances) Pineapple flavouring
powder, orange eg Firmenich Orange, vanilla/lemon and lime e.g. IFF Vanilla and Givaudin Roure
Lemon and Lime Flav-o-lok, fruit punch eg Ungerer fruit punch, citrus punch, mango, and berry.
Those and further suitable flavourings are available from International Flavours and Fragrances Inc.
(Duddery Hill, Haverhill, Suffolk, CB9 8LG, England), Ungerer & Company (Sealand Road, Chester,
England CHI 4LP) or Firmenich (Firmenich UK Ltd., Hayes Road, Southall, Middlesex UB2 5NN).
More preferred flavourings are lemon, kiwi, strawberry, grapefruit, orange, fruit punch and mango.
Citrus flavour, orange grapefruit flavour, mango, fruit punch and orange flavour are particularly
preferred. It is preferred that the flavouring agent is alcohol-free.
The amount of flavouring agent required depends on the nature and strength of the flavouring in
question. Typically, it is 0.05 to 4.5 g per litre, for example 0.05 to 2.0 g per litre, for example 0.2 to
1.8g per litre, for example 1.0 to 1.8g per litre, for example 3.0 to 4.5g per litre, for example 0.3g per
litre or 1.2g per litre, for example 3.2 or 4.2g per litre.
The cleansing solution preferably includes a sweetener. Sugar-based sweeteners are generally not
suited for colon cleansing compositions because the delivery of unabsorbed sugars to the colon
provides a substrate for bacteria. Such sugars may be metabolised by the bacteria to form explosive
gases such as hydrogen and methane. The presence of explosive gases in the colon can be highly
dangerous when electrical apparatus is to be used during colonoscopy or other procedures. Preferred
sweeteners include aspartame, acesulfame potassium (acesulfame K), sucralose and saccharine, and/
or combinations thereof. For example, compositions of the invention may comprise one or both of
aspartame and acesulfame potassium (acesulfame K). For example, compositions of the invention
may comprise one or both of sucralose and acesulfame potassium (acesulfame K). In a preferred
embodiment, the solution comprises aspartame or sucralose, for example aspartame.
Alternatively, compositions of the invention can be essentially free from added sweeteners, for
example to minimize the number of different components in the compositions.
A souring agent (for example citric acid) may be present as a taste enhancer. A souring agent is a
component that imparts a sourness to a composition. Other souring agents include malic acid, acetic
acid, tartaric acid, gluconodeltalactone, phosphoric acid, succinic acid, phytic acid, lactic acid or salts
thereof. The souring agent (for example citric acid) may be provided in an encapsulated form. The
encapsulation provides a coating that isolates the souring agent from other components and from air
and moisture prior to its use. Several encapsulated forms of citric acid, or other souring agents, are
commercially available. For example, the encapsulation may be with a water-soluble coating.
The amount of sweetener required depends on the nature and strength of the sweetener being
considered. Typically, it is 0.10 to 4 g per litre. For example, the sweetener may be aspartame at 0.5
to 4g per litre, for example 2.5 to 4.0 g per litre, for example 3.0g per litre, for example 3.86g per litre.
Those quantities of aspartame are particularly suitable when used with orange flavouring, for example
orange flavouring at 0.2 to 1.8g per litre, for example 1.0 to 1.8g per litre, for example 0.3g per litre,
0.875g per litre or 1.2g per litre. For example, the sweetener may be aspartame at 1.0 to 2.5g per litre,
for example 1.5 to 2.0g per litre, for example 1.75g per litre.
The invention thus 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;
b) 10 to 200 g per litre PEG.
c) one or more electrolytes;
d) optionally one or more alkali metal or alkaline earth metal sulphates;
e) optionally one or more flavouring agents; and
f) optionally one or more sweeteners.
It will be apparent to the reader of this specification, that the term "comprising" and grammatical
variations thereof, in relation to embodiments of the invention described, may be substituted in all
cases (unless the context dictates otherwise) with the term "consisting essentially of or "consisting
of. In the case of a solution that "consists of or "consists essentially of the stated components, the
balance is in each case made up of water.
In particular, 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;
b) 10 to 200 g per litre PEG having an average molecular weight of 3000 to 4000 Da;
c) sodium chloride and potassium chloride;
d) optionally sodium sulphate;
e) optionally one or more flavouring agents; and
f) optionally one or more sweeteners.
Each of c) and d) may be present in the concentrations described above. Each of e) and f) may be as
described above and/or be in the concentrations described above.
In particular, 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;
b) 10 to 200 g per litre PEG having an average molecular weight of 3000 to 4000 Da;
c) sodium chloride and potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners.
In one embodiment, one or more components of c), d) (when present), e) and f) are present in the
solution of the invention. In an alternative presentation, some or all of components c), d) (when
present), e) and f) may be provided separately from the solution of the invention, for example in a
tablet or capsule. For example, components c) and d) may be provided in tablet form. In an
embodiment, the solution of the invention may comprise a) the ascorbate component and b) PEG, and
optional flavouring and sweetener (e) and f)), and a tablet or capsule may comprise c) the one or more
electrolytes (optionally with d), the one or more alkali metal or alkaline earth metal sulphates), again
with optional flavouring and sweetener (e) and f). The flavouring and sweeteners need not be the
same in the tablet or capsule as in the solution.
In one embodiment, the invention provides a colon cleansing solution comprising:
(i) 12 to 20g per litre ascorbic acid and
(ii) 80 to 120g 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 100g per litre PEG having an average molecular weight of 3000 to 4000 Da;
c) 3 to 8g per litre sodium chloride and 1 to 7g per litre potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners.
In an embodiment, the solution of the invention consists essentially of those components; that is to say
that it does not contain any further components in significant quantities. The solution of the invention
may, for example, not contain any sulphate.
For example, the invention provides a colon cleansing solution consisting essentially of:
a)
(i) 14 to 16g per litre ascorbic acid and
(ii) 92 to 100g per litre sodium ascorbate
b) 75 to 85 per litre PEG having an average molecular weight of 3000 to 4000 Da;
c) 6.0 to 6.8g per litre sodium chloride and 2.0 to 2.8g per litre potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners.
For example, the invention provides a colon cleansing solution consisting essentially of:
(i) 15.08g per litre ascorbic acid and
(ii) 96.22g per litre sodium ascorbate
b) 80g per litre PEG having an average molecular weight of 3000 to 4000 Da;
c) 6.4g per litre sodium chloride and 2.4g per litre potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners.
For example, the flavouring and sweetener may be 1.20g per litre orange flavour and 3.86g per litre
aspartame. For example, the flavouring and sweetener may be 3.20g per litre citrus flavour and 1.75g
per litre aspartame. For example, the flavouring and sweetener may be 4.20g per litre orange
grapefruit flavour and 1.75g per litre aspartame.
Preferably, the colon cleansing solution is hyper-osmotic. That is to say that it has a higher osmotic
strength than blood in the human body. It may, for example have a measured osmolality in the range
500 to 2000 mOsmol/kg. For example, the osmolality may be in the range 700 to 1800 mOsmol/kg.
For example, the solutes in 500ml of the solution of the invention may have a measured V(350) value
of from 1000 to 2000ml, for example from 1300 to 2000ml, for example from 1400 to 1900ml, and be
in a volume of 400 to 600ml, for example 500ml. The V(350) value is the volume of water that is
required to provide a solution with an osmolality of 350mOsmol/kg, the total volume being the final
volume after a volume water has been added to a solution having an initial volume.
Osmolality can be measured in various ways. In general, either freezing point depression or vapour-
pressure alteration is used. For example, an Advanced Instruments, Inc Model 3250 osmometer (a
freezing point depression device) can be used. Vapour pressure measurement can also be used, for
example using an ELITech Group Vapro 5600 device. Osmolality values cited herein are preferably
taken to be values measured using a freezing point depression osmometer, for example using an
Advanced Instruments, Inc Model 3250 osmometer following standard operating procedure.
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 PEG having an average molecular weight of 3000 to 4000 Da;
and 500ml of the solution having a V(350) osmolality value of from 1300 to 2300ml.
For example, 500ml of the solution may have a V(350) osmolality value of from 1500 to 2100ml, for
example from 1700 to 2000ml, for example from 1800 to 1900ml.
b) Additional optional contents of solutions
Unless it is stated otherwise, the solutions of the invention may include one or more additional
optional components:
(i) antioxidants
In general it is not necessary for the solutions of the invention to include preservatives or anti
oxidants. Nevertheless, low levels of anti-oxidants or preservatives may be used if required.
(ii) laxatives
In general, the solutions of the invention are effective without the need for any additional active
ingredients. Nevertheless, a further active ingredient may be included if required. For example, a
laxative may be present, for example a stimulant laxative. For example, bisacodyl, castor oil, senna or
bisoxatin may be used. An example of a colon cleansing solution containing bisoxatin is known from
W02013001315.
(iii) Contrast media
For certain uses, one or more contrast media can be included in a solution of the invention.
Examples of contrast media include barium or iodine products, diatrizoate (marketed, for example, as
HYPAQUE 50), metrizoate (marketed, for example, as ISOPAQUE 370), ioxalgate (marketed, for
example, as HEXABRIX), iopamidol (marketed, for example, as ISOVUE 370), iohexol (marketed,
for example, as OMNIPAQUE 350), ioxilan (marketed, for example, as OXILAN 350), iopramide
(marketed, for example, as ULTRA VIST 370), iodixanol (marketed, for example, as VISIPAQUE
320) and/or a diatrizoic acid or its anionic form diatrizoate (also known as amidotrizoic acid, or 3,5-
diacetamido-2,4,6-triiodobenzoic acid; marketed, for example, as HYPAQUE). Alternatively, the
solution of the invention may be used in conjunction with (e.g., simultaneously, before or after)
administration of a contrast agent or contrast media.
(iv) Dyes and stains.
For certain uses (eg fluorescence endoscopy), one or more dyes or stains that are markers of particular
mucosal pathology can be included in a solution of the invention. Stains may be selective . For
example, hexaminolevulinate may be used, for example as its HCl salt (marketed as CYSVIEW).
Other markers of colonic or rectal mucosal pathology can be used. For example methylene blue,
which can stain the normal mucosa yet polyps do not stain and become more clearly visible.
Further dyes and stains that may be mentioned include: Curcumin, Riboflavin, Riboflavin-5'-
phosphate, Tartrazine, Quinoline Yellow, Sunset Yellow, FCF Orange, Yellow S, Cochineal,
Carminic acid, Carmines, Azorubine, Carmoisine, Ponceau 4R, Cochineal Red A, Allura Red AC,
Patent Blu EV, Indigotine, Indigo carmine, Brilliant Blue FCF, Chlorophylls and chlorophyllins,
Copper complexes of chlorophylls and chlorophyllins, Green S, Plain caramel, Brilliant Black BN,
Black PN, Vegetable carbon, Brown HT, Carotenes, Lutein, Beetroot Red, betanin, Anthocyanins,
Calcium carbonate, Titanium dioxide, Iron oxides and hydroxides, Amaranth, Brown F , Erythrosine,
Lithol Rubine B and/or Red 2G. Further dyes and stains that may be mentioned include: acid
fuchsine, Alba red, Alizarin cyanine green F, Alizurol purple S5, Allura Red AC, Alphazurine
FGBrilliant lake red R, Dibromofluorescein, Diiodofluorescein, Eosine, Erythrosine yellowish Na,
Fast green FCF, Flaming red, Fluorescein, Helindone pink CN, Indanthrene blue, Lake bordeaux B,
Lithol rubin B Ca, Naphthol yellow 5, Orange II, Phloxine B, Ponceau 5X, Pyranine concentrated,
Quinizarinegreen 5S, Tetrabromo- fluorescein, Tetrachlorotetrabromo fluorescein, Toney red,
Uranine, Alcian Blue, Anazolene Sodium, Brilliant Green, Cantaxanthin, Carthamin, Citrus Red 2,
Evan's Blue, Fast Green FCF, Indocyanine Green, Methyl Blue, Methylene Blue, N-(p-
Methoxyphenyl)-p- phenylenediamine, Ponceau 3R, Ponceau SX, Pyranine, Rhodamine B, Saunders
Red, Sudan Black B, Sulphan Blue, Tolonium Chloride, and/or Vital Red or equivalents or any
combination thereof.
Alternatively, the solution of the invention may be used in conjunction with (e.g., simultaneously,
before or after) administration of a dye or stain. A dye or a stain may be provided in slow or delayed
release form, for example delayed release methylene blue (for example MMX format of colonic-
released methylene blue developed by Cosmo Pharmaceuticals, Lainate, Italy) may be mentioned.
(v) Surfactants
A surfactant may be included in a solution of the invention. A surfactant may assist in avoiding the
persistence of bubbles in the colon. Such bubbles can interfere with the visualisation of features of
the colon during colonoscopy. Surfactants that may be mentioned include simethicone (or any
mixture of polydimethylsiloxane and silica gel), dimethicone. Colon cleansing solutions containing
simethicone are described in W02009052256.
(vi) Lubricants
A lubricant may be included in a solution of the invention. The inclusion of a lubricant can help with
a colonoscope insertion and facilitation within the performance of the colonoscopy. Suitable
lubricants include glycerol or silicone.
(vii) Biofilm-disrupting compounds
A biofilm disrupting compound may be included in a solution of the invention. A compound that
disrupts biofilms may assist in separating an adherent polysaccharide DNA - containing layer, the so-
Removal of that layer may assist in achieving a cleaner
called "biofilm" from the colonic mucosa.
and/or more easily visualized or stained mucosa.
Biofilm-disrupting components or agents that may be mentioned include enzymes such as
deoxyribonuclease (DNase), N-acetylcysteine, alginate lyase, glycoside hydrolase dispersin B;
Quorum-sensing inhibitors e.g., ribonucleic acid III inhibiting peptide, Salvadora persica extracts,
Competence-stimulating peptide, Patulin and penicillic acid; peptides - cathelicidin-derived peptides,
small lytic peptide, PTP-7 (a small lytic peptide, see e.g., haridia (201 1) J. Microbiol. 49(4):663-8,
Epub 201 1 Sep 2), Nitric oxide, neo- emulsions; ozone, lytic bacteriophages, lactofemn, xylitol
hydrogel, synthetic iron chelators, cranberry components, curcumin, silver nanoparticles. Acetyl- 1 1 -
keto-P-boswellic acid (AKBA), barley coffee components, probiotics, sinefungin, S-
adenosylmethionine, S- adenosyl-homocysteine, Delisea furanones, N-sulfonyl homoserine lactones
and/or macrolide antibiotics or any combination thereof.
Alternatively, the solution of the invention may be used in conjunction with (e.g., simultaneously,
before or after) administration of a biofilm-disrupting compound. A biofilm-disrupting compound
may be administered towards the end of ingestion of the solution of the invention, or shortly after
completion of ingestion of the solution of the invention, so as to disrupt the biofilm most just before
the colonoscopy.
(viii) Organic acids
Some of the osmotic load of the solution of the invention may be provided by an organic acid or salts
of an organic acid other than ascorbic acid. For example, citric acid and/or salts thereof may replace
some or all of the ascorbate in solutions of the invention. Throughout this description, ascorbic acid
may be replaced with citric acid. A salt of ascorbate may be replaced with the salt of citrate. Sodium
citrate, potassium citrate and magnesium citrate are particularly preferred.
c) Uses of solutions of the invention
The solutions of the invention find use in cleansing the colon or bowel. They are also useful in the
treatment of faecal impaction or constipation.
When carrying out a colon or bowel cleansing treatment, a subject typically takes a single dose or a
split dose of cleansing solution. In a split-dose treatment, typically two doses are taken separated by a
time interval, for example an overnight interval. Alternatively, in a split-dose treatment two doses
may be taken on the same day, for example during the day before a diagnostic, therapeutic or surgical
procedure, or during the day of a diagnostic, therapeutic or surgical procedure. Each dose in a split
dose treatment is smaller than the dose in the single dose treatment. In a split dose treatment, the two
doses may each have the same composition, or they may be different.
For a single dose treatment, the solution of the invention may be ingested in a volume of 700 to
1500ml. For example, the subject may ingest from 750ml to 1300ml of the solution, for example 800
to 1200ml, for example 900 to 1100 ml, for example 1000ml. For example 33 or 34 US fluid ounces
may be ingested. In an embodiment, the subject may ingest some additional clear fluid. The
additional clear fluid may be ingested after ingesting the solution of the invention. Alternatively, the
additional clear fluid may be co-administered with the intake of the solution of the invention. By "co
administered" is meant the coordinated ingestion of a solution of the invention with additional clear
fluid; that is to say that the subject ingests some of the solution of the invention but not necessarily the
whole dose, then some additional clear fluid and then more solution of the invention.
For a split dose treatment, the solution of the invention may be taken as one or both of the doses, each
dose having a volume of 200 to 1000ml. For example, the subject may ingest (as one of the doses)
300ml to 1000ml of the solution, for example 300ml to 900ml, for example 300ml to 800ml, for
example 400ml to 700ml, for example 400 to 600ml, for example 450 to 550 ml, for example 500ml.
For example 16 or 17 US fluid ounces may be ingested.
The combined volume of the first and second doses is preferably less than 2 litres. Preferably, it is
1750ml or less, for example 1500ml or less, for example 1250ml or less. For most adult subjects, a
combined volume of more than 500ml is used, for example more than 750ml. For example, a
combined volume of from 500ml to 1750ml is used, for example from 750ml to 1500ml, for example
from 1000ml to 1500ml, for example 1000ml or 1250ml. For example the first dose may have a
volume of 500ml (for example a volume of 16 or 17 US fluid ounces) or 750ml (for example a
volume of 25 or 26 US fluid ounces) and the second dose may have a volume of 500ml (for example a
volume of 16 or 17 US fluid ounces).
In an embodiment, the subject may ingest some additional clear fluid with each or either dose of colon
cleansing solution. The additional clear fluid may be taken after ingesting a dose of the solution.
Alternatively, the additional clear fluid may be co-administered with the intake of a dose of the
solution of the invention; that is to say that the subject ingests some of the solution of the invention
but not necessarily the whole dose, then some clear fluid and then more solution of the invention.
In the method, there is typically a time interval between ingesting the first dose and ingesting the
second dose. Generally, the time interval is at least 4 hours, for example 6 hours or more, for example
8 hours or more. Typically, the time interval is less than 15 hours. The time interval between starting
to take the first dose and starting to take the second dose may be, for example, the time between an
evening and the following morning, for example 12 to 16 hours, for example 14 hours. For example,
the subject may sleep (for example overnight) between taking the first and second doses.
Alternatively, the time interval between ingesting the first dose and ingesting the second dose can be
at least 10 minutes, for example from 10 minutes to 4 hours, for example from 30 minutes to 4 hours,
for example from 30 minutes to two hours. For example, the subject may ingest the first and second
colon cleansing doses the evening before a surgical, therapeutic or diagnostic procedure (hereinafter
"procedure"). For example, the subject may ingest the first and second colon cleansing doses on the
day of a procedure. The time interval between ingesting the first solution and ingesting the second
solution can be determined by the time it takes for the subject to experience a bowel movement. For
example the subject takes the second dose when the first bowel movement has occurred after
completing ingestion of the first solution. Alternatively, the subject ingests the second dose when the
first bowel movement has occurred even if ingestion of the first dose is not complete.
As mentioned above, in a split-dose treatment two doses may be taken on the same day, for example
during the day before a procedure, or during the day of a procedure. The overall process is thus
typically the sequence:
t=0: the subject takes a first dose of cleansing solution over a time t(dl), optionally followed by
additional clear fluid over a time t(cfl );
t=ti: the subject takes a second dose of cleansing solution over a time t(d2), optionally followed by
additional clear fluid over a time t*(cf2);
t= t2: the subject undergoes the surgical, therapeutic or diagnostic procedure.
Each dose of cleansing solution is generally taken over a period of from 10 minutes to 90 minutes, for
example from 15 minutes to 1 hour, for example from 20 minutes to 45 minutes, typically 30 minutes.
Thus t(dl) is for example 10 to 90 minutes, for example 15 minutes to 1 hour, for example 20 to 45
minutes, typically 30 minutes. Similarly, t(d2) is for example 10 to 90 minutes, for example 15
minutes to 1 hour, for example 20 to 45 minutes, typically 30 minutes.
Each drink of additional clear fluid is generally taken over a period of from 10 minutes to 90 minutes,
for example firoml5 minutes to 1 hour, for example from 20 minutes to 45 minutes, typically 30
minutes. Thus t(cfl) is for example 10 to 90 minutes, for example 15 minutes to 1 hour, for example
to 45 minutes, typically 30 minutes. Similarly, t(cf2) is for example 10 to 90 minutes, for example
minutes to 1 hour, for example 20 to 45 minutes, typically 30 minutes.
On some occasions, a subject may take some of the additional clear fluid before completing the
ingestion of the cleansing solution (for example the two solutions might be interspersed). In that
situation, t(dl) and t(cfl) may not be distinct. t(dl) + t(cfl) is thus for example 20 minutes to 3 hours,
for example 30 minutes to 2 hours, for example 40 to 90 minutes, typically 1 hour.
In general, the surgical, therapeutic or diagnostic procedure is carried out within 36 hours (for
example within 24 hours) of the start of the colon cleansing. That is to say that t2 is generally less
than 36 hours, for example less than 24 hours, for example less than 20 hours, for example less than
19, less than 18, less than 17, less than 16, less than 15, less than 14, less than 13, less than 12, less
than 11, less than 10, less than 9, less than 8, less than 7, less than 6, less than 5, less than 4 or less
than 3 hours. Where the colon cleansing procedure is started on the day before the surgical,
therapeutic or diagnostic procedure, t2 is in the range of from 10 to 36 hours; for example from 12 to
24 hours; for example from 12 to 18 hours; for example from 12 to 16 hours. Where the colon
cleansing procedure is started (and completed) on the day of the surgical, therapeutic or diagnostic
procedure, t2 is in the range of from 3 to 14 hours; for example from 3 to 12 hours, for example from
4 to 10 hours, for example from 4 to 8 hours.
The second dose of cleansing solution is generally taken after an interval after the completion of the
first additional clear fluid. The length of the interval t(dose interval) may be expressed as:
t(dose interval) = ti - (t(dl) + t(cfl)).
As mentioned above, the subject may ingest the first and second doses the evening before a surgical,
therapeutic or diagnostic procedure; or the subject may ingest the first and second doses on the day of
a surgical, therapeutic or diagnostic procedure. In either of those circumstances, t(dose interval) is in
the range of from 0 minutes to 8 hours, for example from 10 minutes to 4 hours, for example from 30
minutes to 4 hours, for example from 30 minutes to two hours, for example one hour or two hours.
That is to say that both doses are taken on the same day.
As mentioned above, alternatively, the subject may ingest the first dose in the evening on the day
before a surgical, therapeutic or diagnostic procedure, and may ingest the second dose in the morning
on the day of the surgical, therapeutic or diagnostic procedure. In that circumstance, t(dose interval)
is in the range of from 8 to 20 hours, for example 10 to 16 hours, for example 10 to 14 hours, for
example 12 hours. The t(dose interval) may, for example, be selected from 20,19,18,17,16,15,14,
13, 12, 11, 10, 9, 8, 7, 6, 5,4, 3, 2 or 1 hours.
The surgical, therapeutic or diagnostic procedure is generally carried out after an interval after the
completion of the second additional clear fluid. The length of the interval t(procedure interval) may
be expressed as:
t(procedure interval) = ta - (t! + t(d2) + t(cf2)).
t(procedure interval) should be long enough for sufficient fluid to have passed through the colon to
cleanse it satisfactorily for a colonoscopy examination or other diagnostic procedure, or a therapeutic
or surgical procedure to be carried out. For example, it should be long enough for colonic effluent to
be clear.
For a regimen in which both doses are taken on the day of the surgical, therapeutic or diagnostic
procedure, or for a regimen in which the second dose is taken on the day of the surgical, therapeutic or
diagnostic procedure, t(procedure interval) is from 30 minutes to 10 hours, for example from 1 to 8
hours, for example from 1 to 6 hours.
For a regimen in which both doses are taken on the day before the surgical, therapeutic or diagnostic
procedure, t(procedure interval) is from 8 to 20 hours, for example from 9 to 18 hours, for example
from 10 to 16 hours. The t(procedure interval) may, for example, be selected from 20, 19, 18, 17, 16,
, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 hours.
The invention thus provides a method of cleaning the colon of a subject before a surgical, therapeutic
or diagnostic procedure, in which the subject takes two doses of colon cleansing solution whereby the
first colon cleansing solution is taken over a time period t(dl) followed by optional additional clear
fluid over a time period t(cfl), 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 t2 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). In particular, the invention provides a method in which:
A) t2 is in the range of from 10 to 36 hours (for example from 12 to 24 hours, for example from 12 to
16 hours); 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); and t(procedure interval) is from 8 to 20 hours (for
example from 10 to 16 hours).
B) t2 is in the range of from 10 to 36 hours (for example from 12 to 24 hours, for example from 12 to
16 hours); t(dose interval) is in the range of 8 to 20 hours (for example 10 to 14 hours); and
t(procedure interval) is from 30 minutes to 10 hours (for example from 1 to 6 hours).
C) t2 is in the range of from 3 to 14 hours (for example from 4 to 10 hours); 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); and t(procedure interval) is from 30 minutes to 10 hours (for example from 1 to 6 hours).
In each of regimens A), B) and C), t(dl) is 15 minutes to 1 hour (for example 30 minutes), t(cfl) is 15
minutes to 1 hour (for example 30 minutes), t(d2) is 15 minutes to 1 hour (for example 30 minutes)
and t(cf2) is 15 minutes to 1 hour (for example 30 minutes). Preferably, the second colon cleansing
solution is a solution of the invention described above in section 2, or as described below in section 4.
The first colon cleansing solution may be the same as the second solution, or it may be different, as
set out herein.
During the ingestion of the first or second dose, or during the time interval between the ingestion of
the first dose and the second dose, the subject may additionally take a stimulant laxative (also known
as a prokinetic agent). A stimulant laxative can assist in bringing about good cleansing. Examples of
stimulant laxatives include contact laxatives, for example bisacodyl, castor oil, senna or bisoxatin.
Examples of stimulant laxatives also include additional osmotic agents for example magnesium salts,
for example magnesium citrate. If a stimulant laxative is included in the regimen, the length of the
time interval can be shortened. For example, it may be 10 minutes to 15 hours, for example 1 to 15
hours, for example 1 to 12 hours, for example 2 to 10 hours.
During the time interval between the administration of the first dose and the second dose, it is very
likely that the subject will experience a bowel movement. Advantageously, the subject waits until the
bowel movement has occurred before taking the second dose.
In a split dose treatment, the solution of the invention may be taken for one or for both of the doses.
Preferably, the solution of the invention is taken as the second dose. For example, the subject may
ingest 300ml to 1000ml of the solution of the invention as the second dose, for example 300ml to
900ml, for example 300ml to 800ml, for example 400ml to 700ml, for example 400 to 600ml, for
example 450 to 550 ml, for example 500ml. For example 16 or 17 US fluid ounces may be ingested.
The first dose of a split dose treatment may be a solution of different constitution from the second
dose. Thus, in a preferred embodiment of a split dose colon cleansing treatment, a subject takes a
dose of an initial cleansing solution, optionally followed by some additional clear fluid. After an
interval, the subject then takes a dose of the solution of the invention, optionally followed by some
additional clear fluid.
The volume of additional clear fluid that a subject ingests after the first or second dose may be in a
range with a lower limit of 100ml, 200ml, 300ml, 400ml or 500ml. Preferably, the lower limit is
300ml, 400ml or 500ml. The volume may be in a range with an upper limit of 1200ml, 1100ml,
1000ml, 900ml or 800ml. For example the volume may be in the range 100ml to 1200ml, for
example 200ml to 1100ml, for example 300ml to 1000ml, for example 500ml to 900ml, for example
1000ml, for example 875ml, for example 500ml to 800ml. For example the volume may be in the
range 300 ml to 900 ml, for example 400 ml to 800 ml, for example 500 ml to 800 ml. The additional
clear fluid may be ingested in a volume of at least 500 ml. For example it may be at least 16 or 17 US
fluid ounces. The instructions provided to the subject may suggest that the additional clear fluid is
ingested over a period of approximately one hour, for example in 150 to 200ml fractions every 15 to
20 minutes. The additional clear fluid may be taken after taking a dose of the solution. Alternatively,
the additional clear fluid may be co-administered with the intake of a dose of the solution of the
invention; for example, the subject may ingest clear fluid between fractions of the solution of the
invention; for example the subject may ingest a cup of the solution of the invention, followed by a cup
of additional clear fluid, followed by further cups of the solution of the invention.
A clear fluid for taking as the additional clear fluid, or for use as the clear fluid when making up a
solution, may be any fluid that allows inspection of colonic output. The clear fluid should also not
impede inspection of the colon during the colonoscopy. Typically the clear fluid is a water-based
beverage, including, for example, water, lemonade, cola drinks, cordial drinks, clear fruit juices and
even clear alcohol-containing beverages, for example beer. It is desirable that the clear fluid does not
contain substantial amounts of or essentially any dietary fibre, as such fibre interferes with the
cleansing of the colon according to the present invention. Accordingly, fruit juices, for example
orange juice and kiwi juice, and fruit "squashes" should be strained before use. Clear fruit cordials,
for example lime cordial or tea (for example green tea), are generally suitable. In view of the
desirability of avoiding drinks containing glucose, so as to reduce the risk of explosive concentrations
of hydrogen or methane building up in the gut, "diet" drinks containing no or low sugar are especially
suitable, for example liquid drinks for diabetics, diet Coke (RTM), diet lemonade, dietary carbonated
drinks or dietary cordials. The most preferred clear fluid is water.
Generally subjects are advised not to eat heavy meals before starting the colon cleansing treatment. A
subject may be advised to fast for 12 hours (for example 10 hours, for example 8 hours, for example 6
hours) before starting the colon cleansing treatment. Alternatively, a subject may, for example, be
advised to follow a "white diet" for a day before, or the day of the start of the colon cleansing
procedure. In a "white diet", a subject is instructed to restrict food intake to white and cream-
coloured foods. Foods that are allowed include 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
include coconut, onion, cauliflower, pears, parsnip, semolina, banana and popcorn. As a further
alternative, a subject may be advised to consume only a light meal, for example plain yoghurt, during
that period.
The method of the invention may be used to cleanse the colon prior to carrying out a diagnostic,
therapeutic or surgical procedure on the colon, rectum or anus or elsewhere in the abdomen in a
subject. The subject is most preferably a human. The diagnostic or surgical procedure may, for
example, be colonoscopy (such as cap-assisted colonoscopy and/or narrow-band colonoscopy),
barium enema examination, sigmoidoscopy (for example flexible sigmoidoscopy) or colon surgery.
The method of the invention may be a method of cleansing the colon prior to a surgical or diagnostic
procedure comprising administering the first solution and then after a time interval administering the
second solution prior to said procedure.
The solutions, compositions and kits described herein also find use in the treatment of constipation
and faecal impaction. They also find use in the treatment of severe bacterial infections of the bowel.
The invention thus provides solutions, compositions and kits as described herein for use in the
treatment of constipation or faecal impaction, or in the treatment of severe bacterial infections of the
bowel. The invention also provides methods of treating constipation or faecal impaction, or in the
treating severe bacterial infections of the bowel comprising administration of solutions as described
herein.
As mentioned above, the solutions of the invention find use in cleansing the colon. The invention
provides, in a further aspect, a solution in water of:
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) optionally 10 to 200 g per litre polyethylene glycol,
for use in cleansing the colon of a mammal.
The solution for use in cleansing the colon of a mammal preferably comprises ascorbate anion in a
concentration of: 300-700mmol per litre, for example 350-650mmol per litre, for example 450-600
mmol per litre. As set out above, the ascorbate anion is provided by a mixture of ascorbic acid and
one or more salts of ascorbic acid. Preferred forms of the ascorbate component are as set out above in
section 3a).
In a preferred embodiment, PEG is present. Preferred forms of the PEG and preferred amounts
thereof are as set out above in section 3a).
The solution for use in cleansing the colon of a mammal may additionally comprise one or more of:
c) one or more electrolytes;
d) one or more alkali metal or alkaline earth metal sulphates;
e) one or more flavouring agents;
f) one or more sweeteners.
For example, the solution for use in cleansing the colon of a mammal additionally comprises elements
c), e) and f) from that list.
Preferred electrolytes and preferred amounts thereof are as set out above in section 3a).
Preferred alkali metal or alkaline earth metal sulphates and preferred amounts thereof are as set out
above in section 3a).
Preferred flavouring agents and preferred amounts thereof are as set out above in section 3a).
Preferred sweeteners and preferred amounts thereof are as set out above in section 3a).
For example, the solution in water comprises:
a) 150 to 400 mmol 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) optionally 5 to 100 g PEG.
In particular, the invention provides a solution comprising:
a) 150 to 400 mmol 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;
b) 5 to 100 g PEG having an average molecular weight of 3000 to 4000 Da;
c) sodium chloride and potassium chloride;
d) optionally sodium sulphate;
e) optionally one or more flavouring agents; and
f) optionally one or more sweeteners
for use in cleansing the colon of a mammal.
Each of c) and d) may be as described above and/or be present in the amounts described above in
section 3a). Each of e) and f) may be as described above and/or be in the amounts described above
section 3a).
In particular, the invention provides a solution consisting essentially of:
(i) 14 to 16g per litre ascorbic acid and
(ii) 92 to 100g per litre sodium ascorbate
b) 75 to 85 per litre PEG having an average molecular weight of 3000 to 4000 Da;
c) 6.0 to 6.8g per litre sodium chloride and 2.0 to 2.8g per litre potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners,
for use in cleansing the colon of a mammal.
Each of c) and d) may be as described above and/or be present in the amounts described above in
section 3a). Each of e) and f) may be as described above and/or be in the amounts described above
section 3a).
For example, the invention provides a solution consisting essentially of:
(i) 15.08g per litre ascorbic acid and
(ii) 96.22g per litre sodium ascorbate
b) 80g per litre PEG having an average molecular weight of 3000 to 4000 Da;
c) 6.4g per litre sodium chloride and 2.4g per litre potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners,
for use in cleansing the colon of a mammal.
For example, the flavouring and sweetener may be 1.20g per litre orange flavour and 3.86g per litre
aspartame. For example, the flavouring and sweetener may be 3.20g per litre citrus flavour and 1.75g
per litre aspartame. For example, the flavouring and sweetener may be 4.20g per litre orange
grapefruit flavour and 1.75g per litre aspartame.
As mentioned above, a colon cleansing treatment typically involves a subject taking a single dose or a
split dose of cleansing solution. The volume of solution that a subject takes in a single dose treatment
is described hereinabove. The subject may take some additional clear fluid after taking the solution as
described hereinabove. The volume of solution that a subject takes in a split dose treatment is
described hereinabove. The subject may take some additional clear fluid after each or either dose the
solution as described hereinabove.
d) Compositions for preparing doses of solutions
The invention further provides a composition (for example a dry composition, for example a powder)
for the preparation of a solution of the invention. A composition can be in a quantity for the
preparation of a dose of the solution, for example a 500ml dose (for example a 16 or 17 US fluid
ounce dose). The invention provides a composition for admixture with water, wherein the
composition is optionally presented in two or more parts and comprises:
a) 150 to 400 mmol 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) 5 to 100 g polyethylene glycol.
For example, the components may be in dry powder, granular or other dry form. They may
alternatively be in the form of concentrates or slurries. Components may be in the same or different
physical forms. For example, the composition is a dry composition, for example a dry powder
composition. For example, one or both of components a) and b) are dry powders. In a dry powder, it
is possible for one or more components to be a salt hydrate.
As set out above in section 3 a), the ascorbate anion is provided by a mixture of ascorbic acid and one
or more salts of ascorbic acid. Preferred forms of the ascorbate component are as set out above in
relation to solutions of the invention.
The composition of the invention preferably comprises ascorbate anion in an amount of 150 to
350mmol, for example 175-325mmol, for example 225-300 mmol.
Ascorbic acid has a molecular weight of 176g/mol and sodium ascorbate has a molecular weight of
198g/mol. Accordingly, the 150 to 400 mmol ascorbate anion can be provided by 3.3 to 12.8g
ascorbic acid and 24.3 to 69g sodium ascorbate, for example 5.0 to 10g ascorbic acid and 40 to 60g
sodium ascorbate; for example 6.0 to 10g ascorbic acid and 40 to 60g sodium ascorbate; for example
7.0 to 8.0g ascorbic acid and 44 to 52g sodium ascorbate; for example 7.0 to 8.0g ascorbic acid and 46
to 50g sodium ascorbate.
Potassium ascorbate has a molecular weight of 214g/mol. Accordingly, the 150 to 400 mmol
ascorbate anion can be provided by 3.3 to 12.8g ascorbic acid and 26 to 75g potassium ascorbate, for
example 5.0 to 10g ascorbic acid and 45 to 65g potassium ascorbate; for example 7.0 to 8.0g ascorbic
acid and 47 to 56g sodium ascorbate.
Magnesium ascorbate has a molecular weight of 374.5g/mol and each mole of magnesium ascorbate
provides two moles of ascorbate. Accordingly, the 150 to 400 mmol ascorbate anion can be provided
by 3.3 to 12.8g ascorbic acid and 23 to 65g magnesium ascorbate, for example 5.0 to 10g ascorbic
acid and 38 to 57g magnesium ascorbate; for example 7.0 to 8.0g ascorbic acid and 42 to 49g
magnesium ascorbate.
In solid form, ascorbic acid is typically made up of protonated free ascorbic acid. In calculations of
concentrations of "ascorbate anion" herein, the number of moles of "ascorbate anion" is taken as the
total concentration of all ascorbate anion present, including the proportion that is protonated.
The weight of the ascorbate component may be 20 to 85g, for example 25 to 75g, for example 20 to
60g, for example 50 to 60g.
In an embodiment, the ascorbate component comprises (or consists essentially of) sodium ascorbate
and ascorbic acid. For example, they may be present in a total amount and in a weight ratio as
mentioned immediately above.
Preferred forms of the PEG are as set out above in section 3 a), in relation to solutions of the invention.
The composition comprises 5 to 100 g of PEG. Preferably, the composition comprises 10 to 80g of
PEG, more preferably 20 to 60g, for example 30 to 50g, for example 37.5 to 42.5g, for example 40 g
of PEG.
The composition may additionally comprise one or more of:
c) one or more electrolytes;
d) one or more alkali metal or alkaline earth metal sulphates;
e) one or more flavouring agents; and
f) one or more sweeteners.
Preferred electrolytes are as set out above in section 3 a), in relation to solutions of the invention. For
example, the composition may comprise sodium chloride in an amount of 0.5 to 5g, for example 1.5
to 4 g, for example 2.0 to 3.5g, for example 2.8g or 3.2g. For example, the composition may
comprise potassium chloride in an amount of 0.5 to 5g, for example 0.5 to 3.5 g, for example 0.75 to
2.5g, for example 0.75 to 1.5g,for example 1.0 to 1.4g, for example 1.2g or 1.3g. In an embodiment,
the composition is essentially free from sodium bicarbonate, for example essentially free from any
bicarbonate.
Preferred alkali metal or alkaline earth metal sulphates are as set out above in section 3 a), in relation
to solutions of the invention. For example, the composition may comprise a sulphate component in an
amount of 1 to 10g, for example 2.5 to 7.5g, for example 4 to 7.5g, for example 5 to 7g, for example
6g. The one or more sulphate salts may be provided in any pharmaceutically acceptable form: they
may each be anhydrous, or be in a hydrated form. The weights mentioned herein refer to the weight
of the sulphate salt excluding any water of hydration. A hydrate form may be present in the dry
powder composition, and that composition is still considered "dry" herein. In an alternative preferred
embodiment, the composition does not comprise a sulphate component; that is to say that the
composition is essentially free from alkali metal sulphates and alkaline earth metal sulphates; in
particular essentially free from sodium sulphate, potassium sulphate and magnesium sulphate.
Preferred flavouring agents are as set out above in section 3 a), in relation to solutions of the invention.
For example the amount of flavouring agent may be 0.025 to 2.25g, for example 0.025 to 1.0 g, for
example 0.1 to 0.9g, for example 0.5 to 0.9g, for example 1.5 to 2.25g, for example 0.15g or 0.6g, for
example 1.6 or 2.1
Preferred sweeteners are as set out above in section 3 a), in relation to solutions of the invention. The
amount of sweetener required depends on the nature and strength of the sweetener being considered.
For example the amount of sweetener may be 0.05 to 2 g, for example 0.25 to 2g, for example 1.25 to
2g, for example 1.5g, for example 1.93g. Those quantities of aspartame are particularly suitable when
used with orange flavouring, for example orange flavouring at 0.1 to 0.9g, for example 0.5 to 0.9g, for
example 0.15g, 0.4375g or 0.6g. For example, the sweetener may be aspartame at 0.5 to 1.25g, for
example 0.75 to 1.0g, for example 0.875g.
In particular, the invention provides a composition comprising :
a) 150 to 400 mmol 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;
b) 5 to 100 g PEG having an average molecular weight of 3000 to 4000 Da.
c) sodium chloride and potassium chloride;
d) optionally sodium sulphate;
e) optionally one or more flavouring agents;
f) optionally one or more sweeteners.
Each of c) and d) may be present in the amounts described above. Each of e) and f) may be as
described above and/or be in the amounts described above.
In one embodiment, the invention provides a composition comprising:
(i) 6.0 to 10g ascorbic acid and
(ii) 40 to 60g sodium ascorbate
the components (i) and (ii) being present in a weight ratio of from 1:5063 to 1:7.875;
b) 30 to 50g PEG having an average molecular weight of 3000 to 4000 Da;
c) 1.5 to 4g sodium chloride and 0.5 to 3.5g potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners.
In one embodiment, the invention provides a composition comprising:
a)
(i) 7.43g ascorbic acid and
(ii) 48.1 lg sodium ascorbate
b) 40g PEG having an average molecular weight of 3000 to 4000 Da;
c) 3.20g sodium chloride and 1.20g potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners.
For example, the flavouring and sweetener may be 0.60g orange flavour and 1.93g aspartame. For
example, the flavouring and sweetener may be 1.60g citrus flavour and 0.875g aspartame. For
example, the flavouring and sweetener may be 2.10g orange grapefruit flavour and 0.875g aspartame.
In an embodiment, the composition consists essentially of those components; that is to say that it does
not contain any further components in significant quantities. The composition may, for example, not
contain any sulphate.
One or more of components a) to f) may be presented in solid form, or in semi-solid form (for
example in gel form).
In one embodiment, the one or more components of c), d) (when present), e) and f) are present in the
composition for making up a solution. In an alternative presentation, some or all of components c), d)
(when present), e) and f) may be provided separately from the composition for making up the
solution, for example in a tablet or capsule. In an embodiment, there may be provided the ascorbate
component and PEG, and optional flavouring and sweetener, in a form for admixture with water, and
a tablet or capsule comprising the one or more electrolytes and/or the one or more alkali metal or
alkaline earth metal sulphates, again with optional flavouring and sweetener. The flavouring and
sweeteners need not be the same in the tablet or capsule as in the composition for admixture with
water.
In some embodiments, it is desirable to package the ascorbate and the PEG components separately
from each other.
In an embodiment, the composition can be provided to the subject with a plurality of flavouring
agents (each optionally with one or more sweeteners), each separately packaged. The subject can then
select a preferred flavouring (or flavouring and sweetener combination) according to his or her taste.
The subject also has the choice of not using any flavouring or sweetener at all.
The invention further provides a solution (for example a 500ml dose) prepared by admixing a
composition of the invention with the requisite volume of water.
It will be apparent to the reader that all compounds and compositions described herein are of a nature
and quality suitable for mammalian (especially human) consumption. For example, they are of
pharmaceutical grade. The pharmaceutically acceptable compositions described herein may be
provided in packaged form with instructions for use.
e) Compositions for preparing solutions
In a further aspect, the invention provides a composition comprising the following components in the
following weight ratios:
a) ascorbate anion 0.82 to 4.0 parts 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) polyethylene glycol 1.0 part.
As mentioned above, for example, the components may be in dry powder, granular or other dry form.
They may alternatively be in the form of concentrates or slurries. Components may be in the same or
different physical forms. For example, the composition is a dry composition, for example a dry
powder composition. For example, one or both of components a) and b) are dry powders.
As set out above, the ascorbate anion is provided by a mixture of ascorbic acid and one or more salts
of ascorbic acid. Preferred forms of the ascorbate component are as set out above in section 3 a) in
relation to solutions of the invention.
Preferred forms of the PEG are as set out above in section 3 a) in relation to solutions of the invention.
The composition of the invention preferably comprises ascorbate anion in a weight ratio to PEG of
0.82 to 3.0 :1. More preferably, the weight ratio is 0.9 to 2.0 : 1, for example 1.0 to 1.5 : 1, for
example 1.2 to 1.3 : 1. As set out above, the ascorbate anion is provided by ascorbic acid and a salt of
ascorbic acid in a ratio of 1:4.5 to 1:7.0. The molar ratio of the ascorbic acid and the one or more salts
of ascorbic acid is from 1:4.75 to 1:6.75; more preferably from 1:5.0 to 1:6.0; for example from
1:5.40 to 1:5.80; for example 15:85. The salt of ascorbic acid can be sodium ascorbate. A mixture of
ascorbic acid and sodium ascorbate in a molar ratio of from 1:4.5 to 1:7.0 has ascorbic acid and
sodium ascorbate present in a weight ratio of 1:5.063 to 1:7.875. A more preferred ratio is 1:5.344 to
1:7.594; more preferably from 1:5.625 to 1:6.75; for example from 1:6.075 to 1:6.525, for example
1:6.38.
In a composition in which the weight ratio of ascorbate anion to PEG is 0.82 to 3.0 :1, and in which
the ascorbate anion is provided by ascorbic acid and a sodium ascorbate in a molar ratio of 1:4.5 to
1:7.0, the weight ratio of ascorbic acid : sodium ascorbate : PEG is 0.1031 to 0.5486 : 0.7591-2.970 :
1 . For example, the weight ratio can be 0.12 to 0.30 : 0.9 to 1.9 : 1; more preferably 0.15 to 0.25 : 1.0
to 1.5 : 1; for example 0.185 to 0.190 : 1.15 to 1.25 : 1 ; for example 0.1885 : 1.203 : 1.
The composition may additionally comprise one or more of:
c) one or more electrolytes;
d) one or more alkali metal or alkaline earth metal sulphates;
e) one or more flavouring agents;
f) one or more sweeteners.
Preferred electrolytes are as set out above in section 3a) in relation to solutions of the invention. For
example, the composition may comprise sodium chloride in a weight ratio to PEG of 0.005 to 0.5 :1,
for example 0.01 to 0.3 : 1, for example 0.03 to 0.2 : 1, for example 0.04 to 0.15 : 1, for example 0.05
to 0.1 : 1, for example 0.06 to 0.09 : 1. For example, the composition may comprise potassium
chloride in a weight ratio to PEG of 0.005 to 0.30 :1, for example 0.01 to 0.20 : 1, for example 0.01 to
0.10 : 1, for example 0.02 to 0.04 : 1.
For example, the invention provides a composition comprising the following components in the
following weight ratios :
a) ascorbate anion: 0.82 to 4.0 parts;
b) polyethylene glycol: 1.0 part;
cl) sodium chloride: 0.005 to 1.0 parts; and
c2) potassium chloride: 0.005 to 1.0 parts;
the ascorbate anion being provided by
(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.
The composition is preferably essentially free from sodium bicarbonate. For example, it is essentially
free from any bicarbonate.
Preferred alkali metal or alkaline earth metal sulphates are as set out above in section 3 a) in relation to
solutions of the invention. For example, the composition may comprise a sulphate component (for
example sodium sulphate) in a weight ratio to PEG of 0.01 to 0.50 :1, For example, the composition
may comprise a sulphate component (for example sodium sulphate) in a weight ratio to PEG of 0.02
to 0.25 : 1, for example 0.03 to 0.22 : 1, for example 0.05 to 0.20 : 1, for example 0.10 to 0.20 : 1.
In an embodiment, the composition does not comprise a sulphate component; that is to say that the
composition is essentially free from alkali metal sulphates and alkaline earth metal sulphates; in
particular essentially free from sodium sulphate, potassium sulphate and magnesium sulphate.
Preferred flavouring agents are as set out above in section 3 a) in relation to solutions of the invention.
For example the composition may comprise a flavouring agent in a weight ratio to PEG of 0.0005 to
0.050 : 1, for example 0.001 to 0.025 : 1, for example 0.0025 to 0.020 : 1.
Preferred sweeteners are as set out above in section 3a) in relation to solutions of the invention. For
example the composition may comprise a sweetener in a weight ratio to PEG of 0.0005 to 0.1 : 1, for
example 0.001 to 0.075 : 1, for example 0.002 to 0.050 : 1.
In particular, the invention provides a composition comprising the following components in the
following weight ratios:
a) ascorbate anion: 0.82 to 4.0 parts
b) PEG having an average molecular weight of 3000 to 4000 Da: 1.0 part.
c) sodium chloride and potassium chloride;
d) optionally sodium sulphate;
e) optionally one or more flavouring agents; and
f) optionally one or more sweeteners;
the ascorbate anion being provided by
(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.
Each of c) and d) may be present in the weight ratios to PEG described above. Each of e) and f) may
be as described above and/or be in the weight ratios to PEG described above.
In one embodiment, the invention provides a composition comprising the following components in
the following weight ratios:
(i) ascorbic acid: 0.12 to 0.30 parts; and
(ii) sodium ascorbate: 0.9 to 1.9 parts
the components (i) and (ii) being present in a weight ratio of from 1:5063 to 1:7.875;
b) PEG having an average molecular weight of 3000 to 4000 Da: 1 part
c) sodium chloride 0.05 to 0.10 parts and litre potassium chloride 0.02 to 0.04 parts;
e) one or more flavouring agents: 0.001 to 0.075 parts; and
f) one or more sweeteners: 0.002 to 0.050 parts.
For example, the composition may comprise the following components in the following weight ratios:
(i) ascorbic acid: 0.189 parts; and
(ii) sodium ascorbate: 1.20 parts
b) PEG having an average molecular weight of 3000 to 4000 Da: 1 part
c) sodium chloride 0.08 parts and litre potassium chloride 0.03 parts;
e) one or more flavouring agents: 0.001 to 0.075 parts; and
f) one or more sweeteners: 0.002 to 0.050 parts.
For example, the flavouring and sweetener may be 0.015parts orange flavour and 0.048parts
aspartame. For example, the flavouring and sweetener may be 0.040parts citrus flavour and
0.022parts aspartame. For example, the flavouring and sweetener may be 0.053parts orange
grapefruit flavour and 0.022parts aspartame.
In an embodiment, the composition consists essentially of those components; that is to say that it does
not contain any further components in significant quantities. The composition may, for example, not
contain any sulphate.
Preferred compositions of the invention are dry compositions, for example dry powder compositions.
In a further aspect, the invention provides a composition comprising the following components in the
following weight ratios:
(i) ascorbic acid: 1 part and
one or more salts of ascorbic acid: 5.063 to 7.875parts
The salt of ascorbic acid can be sodium ascorbate. A mixture of ascorbic acid and sodium ascorbate
in a molar ratio of from 1:4.5 to 1:7.0 has ascorbic acid and sodium ascorbate present in a weight ratio
of 1:5.063 to 1:7.875. A more preferred ratio is 1:5.344 to 1:7.594; more preferably from 1:5.625 to
1:6.75; for example from 1:6.075 to 1:6.525, for example 1:6.38.
f) Methods of preparing solutions and compositions
The invention further provides a method of preparing a solution of the invention comprising
combining the components of the solution with water. The method comprises the step of combining
the components with water and admixing. Some or all of the components may be in physical
association with each other before the water is added. In some embodiments, the components of the
composition are provided in more than one part; that is to say that they are packaged separately. All
of the components may be combined with each other before combining with water. For example, if
flavouring agent and sweetener are packaged separately from other components, they may be
combined with the other components before combining with water. One or some of the components
may be combined with water and admixed in a first step and then some or all of the remaining
components may be added in a second step. For example, the components may be in dry form, for
example in powder form.
As set out above in section 3d), the invention provides a composition (for example a dry composition,
for example a powder) for the preparation of a solution of the invention. The invention further
provides a method of preparing a composition of the invention comprising combining the components
of the composition. For example, the method may be a method of preparing a composition of the
invention in powder form. As set out in section 3d) above, the components for the preparation of a
solution of the invention may be presented in two or more parts. The invention thus further provides a
method of preparing a composition of the invention comprising combining some, but not all of the
components of the composition. The invention thus provides a method comprising blending a mixture
(i) ascorbic acid: 1 part and
one or more salts of ascorbic acid: 5.063 to 7.875parts
The salt of ascorbic acid can be sodium ascorbate. A mixture of ascorbic acid and sodium ascorbate
in a molar ratio of from 1:4.5 to 1:7.0 has ascorbic acid and sodium ascorbate present in a weight ratio
of 1:5.063 to 1:7.875. A more preferred ratio is 1:5.344 to 1:7.594; more preferably from 1:5.625 to
1:6.75; for example from 1:6.075 to 1:6.525, for example 1:6.38.
The method may comprise blending 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.
Preferred salts of ascorbic acid are as set out above in section 3a). Preferred ratios of components (i)
and (ii) are as set out above in section 3a).
The method may further comprise blending a mixture of:
a) ascorbate anion: 0.82 to 4.0 parts;
b) polyethylene glycol: 1.0 part;
cl) sodium chloride: 0.005 to 1.0 parts; and
c2) potassium chloride: 0.005 to 1.0 parts;
the ascorbate anion being provided by
(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.
The components may be weighed out and added together before blending, or the components may be
added into a blend mixture in any desired order.
Blending of the compositions in bulk may, for example, be carried out on a lOOKg, 500Kg or
lOOOKg scale. After blending, the composition is divided into smaller portions for packaging into
dosage amounts. The invention thus provides a method comprising the step of dividing bulk
composition as set out in section 3e) above into smaller portions. The invention also provides a
method comprising the step of filling containers with individual dosage amounts of bulk composition
as set out in section 3e). The invention thus provides a method comprising the step of filling a
container with a composition as set out in section 3d). The composition as set out in section 3d) may
be presented in two or more parts. The method may thus comprise the step of filling a container with
some but not all of the components of a composition as set out in section 3d).
4. Alternative solutions
The invention also provides a colon cleansing solution that does not contain any ascorbic acid. The
invention thus provides, in a second aspect, a colon cleansing solution comprising:
a) 360 to 440 mmol per litre ascorbate anion provided by one or more salts of ascorbic acid
b) 10 to 200 g per litre polyethylene glycol;
the solution being essentially free from ascorbic acid.
The solution of the invention has advantageous properties. The solution of the invention has a
surprisingly palatable taste and it is highly effective as a colon cleansing solution with a good
tolerability profile.
5. Detailed description II
This section describes in further detail the solutions set out in section 4 immediately above.
a) Contents of solutions
The solutions of the invention are aqueous solutions. Suitable salts of ascorbic acid include alkali
metal salts and alkaline earth metal salts. For example a salt may be selected from sodium,
potassium, magnesium and calcium salts. For example, preferred salts of ascorbic acid include
sodium ascorbate, potassium ascorbate, magnesium ascorbate and calcium ascorbate. Particularly
preferred salts of ascorbic acid are magnesium ascorbate and sodium ascorbate, for example sodium
ascorbate. In one embodiment, the solution comprises sodium ascorbate and no further ascorbate.
The solution of the invention preferably comprises ascorbate anion in a concentration of: 370-
430mmol per litre, for example 380-420mmol per litre, for example 400-410 mmol per litre.
A solution of the invention may comprise 72 to 88g/litre of ascorbate salt. For example, a solution of
the invention comprises 75 to 85g/litre, for example 78 to 82g/litre, for example 80g/litre.
Sodium ascorbate has a molecular weight of 198g/mol. Accordingly, a solution of the invention may
comprise sodium ascorbate at 71.3 - 87.Ig per litre, for example 73.3-85.Ig per litre for example
75.2-83.2g per litre, for example 79.2-80.2g per litre.
Potassium ascorbate has a molecular weight of 214g/mol. Accordingly, a solution of the invention
may comprise potassium ascorbate at 77.0-94.2g per litre, 79.2-92.Og per litre, for example 81.3-89.9g
per litre, for example 85.6-86.7g per litre.
Magnesium ascorbate has a molecular weight of 374.5g/mol and each mole of magnesium ascorbate
provides two moles of ascorbate. Accordingly, a solution of the invention may comprise magnesium
ascorbate at 67.4-82.4g per litre, for example 69.3-80.5g per litre, for example 71.2-78.6g per litre, for
example 74.9-75.8g per litre.
Depending on the pH of the solution, some ascorbate anion may be protonated and thus exist as free
ascorbic acid in solution. At the pH of solutions that would typically be administered, only a minor
proportion of ascorbate is protonated. In calculations of concentrations of "ascorbate anion" herein,
the concentration of "ascorbate anion" is taken as the total concentration of all ascorbate anion
present, including the proportion that is protonated.
The cleansing solution comprises polyethylene glycol. The polyethylene glycol (PEG) may be as
described above in section 3a). The cleansing solution comprises 10 to 200 g per litre of PEG.
Preferably, the solution comprises 20 to 160g per litre of PEG, more preferably 40 to 120 g per litre,
for example 60 to 100 g per litre, for example 75 to 85 g per litre, for example 80 g per litre.
The cleansing solution may additionally comprise one or more of:
c) one or more electrolytes;
d) one or more alkali metal or alkaline earth metal sulphates;
e) one or more flavouring agents;
f) one or more sweeteners.
The cleansing solution may comprise one or more electrolytes. Electrolytes include salts of sodium,
potassium, calcium and magnesium, particularly sodium and potassium; and salts of chloride, iodide,
bicarbonate and carbonate, particularly chloride. Preferred electrolytes are sodium chloride and
potassium chloride. In an embodiment, the solution is essentially free from sodium bicarbonate, for
example essentially free from any bicarbonate.
For example, the solution may comprise sodium chloride at a concentration of 1 to 10 g per litre. For
example, sodium chloride may be present at a concentration of 3 to 8 g per litre, for example 4 to 7g
per litre; for example 4.5 to 5.5g per litre; for example 5.0g per litre or 5.6g per litre.
For example, the solution may comprise potassium chloride at a concentration of 1 to 10 g per litre.
For example, potassium chloride may be present at a concentration of 1 to 7 g per litre, for example
1.5 to 5g per litre, for example 1.5 to 3g per litre, for example 1.7 to 2.8 g per litre; for example 1.8g
per litre or 2.6g per litre.
In an embodiment, the solution comprises sodium chloride and potassium chloride. They can be
present in the amounts mentioned immediately above. For example, sodium chloride may be present
at a concentration of 4 to 7g per litre and potassium chloride may be present at a concentration of 1.5
to 3g per litre.
The cleansing solution may comprise one or more alkali metal sulphates, alkaline earth metal
sulphates or a mixture thereof (herein referred to as a "sulphate component"). The sulphate
component and the quantity thereof may be as described above in section 3a).
In an alternative preferred embodiment, the solution does not comprise a sulphate component; that is
to say that the solution is essentially free from alkali metal sulphates and alkaline earth metal
sulphates; in particular essentially free from sodium sulphate, potassium sulphate and magnesium
sulphate.
In the solutions of the invention described herein, the quantities of the individual components recited
do not include any solutes that may be present in the water used to prepare the solutions, for example,
in hard water areas there may be significant amounts of Ca2+ and Mg2+ carbonates, bicarbonates or
sulphates present in tap water.
The cleansing solution preferably includes a flavouring agent. The flavouring may be as described
above in section 3a). Lemon/lime flavour and orange flavour are particularly preferred.
The amount of flavouring required depends on the nature and strength of the flavouring in question.
Typically, it is 0.05 to 4.5 g per litre, for example 0.05 to 2.0 g per litre, for example 0.5 to 1.8g per
litre, for example 2.5 to 4.5g per litre, for example 0.6g per litre or 1.6g per litre, for example 3.2 or
4.3g per litre.
The cleansing solution preferably includes a sweetener. The sweetener may be as described above in
section 3a).
Alternatively, compositions of the invention can be essentially free from added sweeteners, for
example to minimize the number of different components in the compositions.
A souring agent (for example citric acid) may be present as a taste enhancer. A souring agent is a
component that imparts a sourness to a composition. Other souring agents include malic acid, acetic
acid, tartaric acid, gluconodeltalactone, phosphoric acid, succinic acid, phytic acid, lactic acid or salts
thereof. The souring agent (for example citric acid) may be provided in an encapsulated form. The
encapsulation provides a coating that isolates the souring agent from other components and from air
and moisture prior to its use. Several encapsulated forms of citric acid, or other souring agents, are
commercially available. For example, the encapsulation may be with a water-soluble coating.
The amount of sweetener required depends on the nature and strength of the sweetener being
considered. Typically, it is 0.10 to 4 g per litre. For example, the sweetener may be aspartame at 0.5
to 4g per litre, for example 2.5 to 4.0 g per litre, for example 2.0g per litre, for example 2.2g per litre
or 3.25g per litre. Those quantities of aspartame are particularly suitable when used with orange
flavouring, for example orange flavouring at 0.2 to 1.8g per litre, for example 0.5 to 1.8g per litre, for
example 0.6g per litre or 1.6g per litre or 3.25g per litre.
The invention thus provides a colon cleansing solution comprising:
a) 360 to 440 mmol per litre ascorbate anion provided by one or more salts of ascorbic acid;
b) 10 to 200 g per litre PEG;
c) one or more electrolytes;
d) optionally one or more alkali metal or alkaline earth metal sulphates;
e) optionally one or more flavouring agents; and
f) optionally one or more sweeteners;
the solution being essentially free from ascorbic acid.
In particular, the invention provides a colon cleansing solution comprising:
a) 360 to 440 mmol per litre ascorbate anion provided by one or more salts of ascorbic acid;
b) 10 to 200 g per litre PEG having an average molecular weight of 3000 to 4000 Da;
c) sodium chloride and potassium chloride;
d) optionally sodium sulphate;
e) optionally one or more flavouring agents; and
f) optionally one or more sweeteners;
the solution being essentially free from ascorbic acid.
Each of c) and d) may be present in the concentrations described above. Each of e) and f) may be as
described above and/or be in the concentrations described above.
In particular, the invention provides a colon cleansing solution comprising:
a) 360 to 440 mmol per litre ascorbate anion provided by one or more salts of ascorbic acid;
b) 10 to 200 g per litre PEG having an average molecular weight of 3000 to 4000 Da;
c) sodium chloride and potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners;
the solution being essentially free from ascorbic acid.
In one embodiment, the one or more components of c), d) (when present), e) and f) are present in the
solution. In an alternative presentation, some or all of components c), d) (when present), e) and f)
may be provided separately from the solution, for example in a tablet or capsule. In an embodiment,
the solution may comprise a) the ascorbate component and b) PEG, and optional flavouring and
sweetener (e) and f)), and a tablet or capsule may comprise c) the one or more electrolytes and/or d)
the one or more alkali metal or alkaline earth metal sulphates, again with optional flavouring and
sweetener (e) and f)). The flavouring and sweeteners need not be the same in the tablet or capsule as
in the solution.
In one embodiment, the invention provides a colon cleansing solution comprising:
a) 71.3 to 87.1 g per litre sodium ascorbate
b) 60 to 100g per litre PEG having an average molecular weight of 3000 to 4000 Da;
c) 3 to 8g per litre sodium chloride and 1 to 7g per litre potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners.
In an embodiment, the solution consists essentially of those components; that is to say that it does not
contain any further components in significant quantities. The solution may, for example, not contain
any sulphate.
In particular, the invention provides a solution consisting essentially of:
a) 75 to 85g per litre sodium ascorbate
b) 75 to 85 per litre PEG having an average molecular weight of 3000 to 4000 Da;
c) 4.5 to 5.5g per litre sodium chloride and 1.5 to 2.3g per litre potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners.
For example, the invention provides a colon cleansing solution consisting essentially of:
a) 80g per litre sodium ascorbate
b) 80g per litre PEG having an average molecular weight of 3000 to 4000 Da;
c) 5.0g per litre sodium chloride and 1.80g per litre potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners.
For example, the flavouring and sweetener may be 1.60g per litre orange flavour and 2.20g per litre
aspartame. For example, the flavouring and sweetener may be 3.20g per litre lemon/lime flavour and
3.25g per litre aspartame. For example, the flavouring and sweetener may be 4.30g per litre orange
grapefruit flavour and 3.25g per litre aspartame.
Preferably, the colon cleansing solution is hyper-osmotic. That is to say that it has a higher osmotic
strength than blood in the human body. It may, for example have a measured osmolality in the range
500 to 2000 mOsmol/kg. For example, the osmolality may be in the range 700 to 1800 mOsmol/kg.
For example, the solutes in 500ml of the solution may have a measured V(350) value of from 1000 to
2000ml, for example from 1300 to 1700ml, for example from 1400 to 1600ml, and be in a volume of
400 to 600ml, for example 500ml.
The invention provides a colon cleansing solution comprising:
a) 360 to 440 mmol per litre ascorbate anion provided by one or more salts of ascorbic acid
b) 10 to 200 g per litre polyethylene glycol;
the solution being essentially free from ascorbic acid, and 500ml of the solution having a V(350)
osmolality value of from 1000 to 2000ml.
For example, 500ml of the solution may have a V(350) osmolality value of from 1200 to 1800ml, for
example from 1400 to 1600ml.
b) Additional optional contents of solutions
The solutions of the invention may include additional optional components as set out above in section
c) Uses of solutions of the invention
Uses of solutions of the invention are as set out above in section 3c). The invention thus provides, in
a further aspect a solution in water of:
a) 360 to 440 mmol per litre ascorbate anion provided by one or more salts of ascorbic acid; and
b) optionally 10 to 200 g per litre polyethylene glycol.
the solution being essentially free from ascorbic acid,
for use in cleansing the colon of a mammal.
The solution for use in cleansing the colon of a mammal preferably comprises ascorbate anion in a
concentration of: 370-430mmol per litre, for example 380-420mmol per litre, for example 400-410
mmol per litre. As set out above, the ascorbate anion is provided by one or more salts of ascorbic
acid. Preferred forms of the ascorbate component are as set out above in section 5a).
In a preferred embodiment, PEG is present. Preferred forms of the PEG and preferred amounts
thereof are as set out above in section 5a).
The solution for use in cleansing the colon of a mammal may additionally comprise one or more of:
c) one or more electrolytes;
d) one or more alkali metal or alkaline earth metal sulphates;
e) one or more flavouring agents;
f) one or more sweeteners.
For example, the solution for use in cleansing the colon of a mammal additionally comprises elements
c), e) and f) from that list.
Preferred electrolytes and preferred amounts thereof are as set out above in section 5a).
Preferred alkali metal or alkaline earth metal sulphates and preferred amounts thereof are as set out
above in section 5a).
Preferred flavouring agents and preferred amounts thereof are as set out above in section 5a).
Preferred sweeteners and preferred amounts thereof are as set out above in section 5a).
For example, the solution in water comprises:
a) 180 to 220 mmol ascorbate anion provided by one or more salts of ascorbic acid; and
b) optionally 5 to 100 g PEG.
the solution being essentially free from ascorbic acid.
In particular, the invention provides a solution comprising :
a) 180 to 220 mmol ascorbate anion provided by one or more salts of ascorbic acid;
b) 5 to 100 g PEG having an average molecular weight of 3000 to 4000 Da;
c) sodium chloride and potassium chloride;
d) optionally sodium sulphate;
e) optionally one or more flavouring agents; and
f) optionally one or more sweeteners,
the solution being essentially free from ascorbic acid
for use in cleansing the colon of a mammal.
Each of c) and d) may be as described above and/or be present in the amounts described above in
relation to solutions of the invention. Each of e) and f) may be as described above and/or be in the
amounts described above in section 5a).
In particular, the invention provides a solution consisting essentially of:
a) 75 to 85g per litre sodium ascorbate
b) 75 to 85 per litre PEG having an average molecular weight of 3000 to 4000 Da;
c) 4.5 to 5.5g per litre sodium chloride and 1.5 to 2.3g per litre potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners,
for use in cleansing the colon of a mammal.
For example, the invention provides a solution consisting essentially of:
a) 80g per litre sodium ascorbate
b) 80g per litre PEG having an average molecular weight of 3000 to 4000 Da;
c) 5.0g per litre sodium chloride and 1.80g per litre potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners.
for use in cleansing the colon of a mammal.
For example, the flavouring and sweetener may be 1.60g per litre orange flavour and 2.20g per litre
aspartame. For example, the flavouring and sweetener may be 3.20g per litre lemon/lime flavour and
3.25g per litre aspartame. For example, the flavouring and sweetener may be 4.30g per litre orange
grapefruit flavour and 3.25g per litre aspartame.
As mentioned above, a colon cleansing treatment typically involves a subject taking a single dose or a
split dose of cleansing solution. The volume of solution that a subject takes in a single dose treatment
is described hereinabove in section 3c). The subject may take some additional clear fluid after taking
the solution as described hereinabove.
The volume of solution that a subject takes in a split dose treatment is described hereinabove in
section 3c). The subject may take some additional clear fluid after each or either dose the solution as
described hereinabove.
d) Compositions for preparing doses of solutions
The invention further provides a composition (for example a dry composition, for example a powder)
for the preparation of a solution of the invention. A composition can be provided in a quantity for the
preparation of a dose of the solution, for example a 500ml dose. The invention provides a
composition for admixture with water, wherein the composition is optionally presented in two or more
parts and comprises:
a) 180 to 220 mmol ascorbate anion provided by one or more salts of ascorbic acid; and
b) 5 to 100 g polyethylene glycol;
the solution being essentially free from ascorbic acid.
For example, the components may be in dry powder, granular or other dry form. They may
alternatively be in the form of concentrates or slurries. Components may be in the same or different
physical forms. For example, the composition is a dry composition, for example a dry powder
composition. For example, one or both of components a) and b) are dry powders.
As set out above in section 5a), the ascorbate anion may be provided by one or more salts of ascorbic
acid. Preferred forms of the ascorbate component are as set out above in relation to solutions of the
invention.
The composition of the invention preferably comprises ascorbate anion in an amount of: 185 to
215mmol, for example 190 to 210mmol, for example 200-205 mmol.
Sodium ascorbate has a molecular weight of 198g/mol. Accordingly, the 180 to 220 mmol ascorbate
anion can be provided by 35.6 to 43.6g sodium ascorbate. For example, the sodium ascorbate may be
present at a level of 36.6 to 42.6g, for example 37.6 to 41.6g, for example 39.6 to 40.6g.
Potassium ascorbate has a molecular weight of 214g/mol. Accordingly, the 180 to 220 mmol
ascorbate anion can be provided by 38.5 to 47.Ig potassium ascorbate. For example, the potassium
ascorbate may be present at a level of 39.6 to 46.0g, for example 40.7 to 44.9g, for example 42.8 to
43.9g.
Magnesium ascorbate has a molecular weight of 374.5g/mol and each mole of magnesium ascorbate
provides two moles of ascorbate. Accordingly, the 180 to 220 mmol ascorbate anion can be provided
by 33.7 to 41.2g magnesium ascorbate. For example, the magnesium ascorbate may be present at a
level of 34.6 to 40.3g, for example 35.6 to 39.3g, for example 37.5 to 38.4g.
The weight of the ascorbate salt component may be 33 to 47g, for example 35 to 45g, for example 37
to 43g.
In an embodiment, the ascorbate component consists essentially of sodium ascorbate alone. For
example, it may be present in an amount as mentioned immediately above.
Preferred forms of the PEG are as set out in section 5a) above in relation to solutions of the invention.
The composition comprises 5 to 100 g of PEG. Preferably, the composition comprises 10 to 80g of
PEG, more preferably 20 to 60g, for example 30 to 50g, for example 37.5 to 42.5g, for example 40 g
of PEG.
The composition may additionally comprise one or more of:
c) one or more electrolytes;
d) one or more alkali metal or alkaline earth metal sulphates;
e) one or more flavouring agents; and
f) one or more sweeteners.
Preferred electrolytes are as set out above in section 5a) in relation to solutions of the invention. For
example, the composition may comprise sodium chloride in an amount of 0.5 to 5g, for example 1.5
to 4 g, for example 2.0 to 3.5 g, for example 2.5 or 2.8g. For example, the composition may comprise
potassium chloride in an amount of 0.5 to 5g, for example 0.5 to 3.5 g, for example 0.75 to 2.5g, for
example 0.75 to 1.5g, for example 0.85 to 1.4g, for example 0.9 or 1.3g. In an embodiment, the
composition is essentially free from sodium bicarbonate, for example essentially free from any
bicarbonate.
Preferred alkali metal or alkaline earth metal sulphates are as set out above in relation to solutions of
the invention. For example, the composition may comprise a sulphate component in an amount of 1
to 10g, for example 2.5 to 7.5g, for example 4 to 7.5g, for example 5 to 7g, for example 6g. The one
or more sulphate salts may be provided in any pharmaceutically acceptable form: they may each be
anhydrous, or be in a hydrated form. The weights mentioned herein refer to the weight of the sulphate
salt excluding any water of hydration. A hydrate form may be present in the dry powder composition,
and that composition is still considered "dry" herein. In an alternative preferred embodiment, the
composition does not comprise a sulphate component; that is to say that the solution is essentially free
from alkali metal sulphates and alkaline earth metal sulphates; in particular essentially free from
sodium sulphate, potassium sulphate and magnesium sulphate.
Preferred flavouring agents are as set out above in section 5a) in relation to solutions of the invention.
For example the amount of flavouring agent may be 0.025 to 2.25g, for example 0.025 to 1.0 g, for
example 0.25 to 0.9g, for example 1.25 to 2.25g, for example 0.3g or 0.8g, for example 1.6 or 2.15g.
Preferred sweeteners are as set out above in relation to solutions of the invention. For example the
amount of sweetener may be 0.05 to 2 g. For example, the sweetener may be aspartame at 0.25 to 2g,
for example at 1.25 to 2.0 g, for example 1.0, l.lg or 1.625g. Those quantities of aspartame are
particularly suitable when used with orange flavouring, for example orange flavouring at 0.1 to 0.9 g,
for example 0.25 to 0.9 g, for example 0.3, 0.8 g or 1.625g.
In particular, the invention provides a composition comprising:
a) 180 to 220 mmol ascorbate anion provided by one or more salts of ascorbic acid;
b) 5 to 100 g PEG having an average molecular weight of 3000 to 4000 Da.
c) sodium chloride and potassium chloride;
d) optionally sodium sulphate;
e) optionally one or more flavouring agents;
f) optionally one or more sweeteners;
the solution being essentially free from ascorbic acid.
Each of c) and d) may be present in the amounts described above. Each of e) and f) may be as
described above and/or be in the amounts described above.
In one embodiment, the invention provides composition comprising:
a) 35.65 to 43.55g sodium ascorbate
b) 30 to 50g PEG having an average molecular weight of 3000 to 4000 Da;
c) 1.5 to 4g sodium chloride and 0.5 to 3.5g potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners.
In one embodiment, the invention provides a composition comprising:
a) 40g sodium ascorbate
b) 40g PEG having an average molecular weight of 3000 to 4000 Da;
c) 2.50g sodium chloride and 0.90g potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners.
For example, the flavouring and sweetener may be 0.80g orange flavour and 1.10g aspartame. For
example, the flavouring and sweetener may be 1.60g lemon/lime flavour and 1.625g aspartame. For
example, the flavouring and sweetener may be 2.15g orange grapefruit flavour and 1.625g aspartame.
In an embodiment, the composition consists essentially of those components; that is to say that it does
not contain any further components in significant quantities. The composition may, for example, not
contain any sulphate.
One or more components a) to f) may be presented in solid form, or in semi-solid form (for example
in gel form).
In one embodiment, the one or more components of c), d) e) and f) are present in the composition for
making up a solution. In an alternative presentation, some or all of components c), d) e) and f) may
be provided separately from the composition for making up the solution, for example in a tablet or
capsule. In an embodiment, there may be provided the ascorbate component and PEG, and optional
flavouring and sweetener, in a form for admixture with water, and a tablet or capsule comprising the
one or more electrolytes and/or the one or more alkali metal or alkaline earth metal sulphates, again
with optional flavouring and sweetener. The flavouring and sweeteners need not be the same in the
tablet or capsule as in the composition for admixture with water.
In some embodiments, it is desirable to package the ascorbate and the PEG components separately
from each other.
In an embodiment, the composition can be provided to the subject with a plurality of flavouring
agents (each optionally with one or more sweeteners), each separately packaged. The subject can then
select a preferred flavouring (or flavouring and sweetener combination) according to his or her taste.
The subject also has the choice of not using any flavouring or sweetener at all.
It will be apparent to the reader that all compounds and compositions described herein are of a nature
and quality suitable for mammalian (especially human) consumption. For example, they are of
pharmaceutical grade. The pharmaceutically acceptable compositions described herein may be
provided in packaged form with instructions for use.
e) Compositions for preparing solutions
In a further aspect, the invention provides a composition comprising the following components in the
following weight ratios:
a) ascorbate anion 0.78 to 1.2 parts; and
b) polyethylene glycol 1.0 part;
the ascorbate anion being provided by one or more salts of ascorbic acid;
the composition being essentially free from ascorbic acid.
As mentioned above, for example, the components may be in dry powder, granular or other dry form.
They may alternatively be in the form of concentrates or slurries. Components may be in the same or
different physical forms. For example, the composition is a dry composition, for example a dry
powder composition. For example, one or both of components a) and b) are dry powders.
As set out above, the ascorbate anion is provided by one or more salts of ascorbic acid. Preferred
forms of the ascorbate component are as set out above in section 5a) in relation to solutions of the
invention. Preferred salts are sodium, potassium and magnesium ascorbate, especially sodium
ascorbate.
Preferred forms of the PEG are as set out above in section 5a) in relation to solutions of the invention.
The composition of the invention preferably comprises ascorbate anion in a weight ratio to PEG of
0.80 to 1.0 :1. More preferably, the weight ratio is 0.85 to 0.95 : 1, for example 0.86 to 0.90 : 1, for
example 0.88 :1.
The preferred ascorbate salt is sodium ascorbate. The composition of the invention preferably
comprises sodium ascorbate and PEG in a weight ratio of 0.90 to 1.125 :1. More preferably, the
weight ratio is 0.956 to 1.069 : 1, for example 0.968 to 1.013: 1, for example 0.99 :1, for example 1:1.
The composition may additionally comprise one or more of:
c) one or more electrolytes;
d) one or more alkali metal or alkaline earth metal sulphates;
e) one or more flavouring agents;
f) one or more sweeteners.
Preferred electrolytes are as set out above in section 5a) in relation to solutions of the invention. For
example, the composition may comprise sodium chloride in a weight ratio to PEG of 0.005 to 0.5 :1,
for example 0.01 to 0.3 : 1, for example 0.02 to 0.2 : 1, for example 0.03 to 0.15 : 1, for example 0.04
to 0.1 : 1, for example 0.05 to 0.08 : 1. For example, the composition may comprise potassium
chloride in a weight ratio to PEG of 0.005 to 0.30 :1, for example 0.01 to 0.20 : 1, for example 0.01 to
0.10 : 1, for example 0.02 to 0.04 : 1.
For example, the invention provides a composition comprising the following components in the
following weight ratios:
a) ascorbate anion: 0.78 to 1.2 parts;
b) polyethylene glycol: 1.0 part;
cl) sodium chloride: 0.005 to 1.0 parts; and
c2) potassium chloride: 0.005 to 1.0 parts;
the ascorbate anion being provided by one or more salts of ascorbic acid;
the composition being essentially free from ascorbic acid.
The composition is preferably essentially free from sodium bicarbonate. For example, it is essentially
free from any bicarbonate.
Preferred alkali metal or alkaline earth metal sulphates are as set out above in section 5a) in relation to
solutions of the invention. For example, the composition may comprise a sulphate component (for
example sodium sulphate) in a weight ratio to PEG of 0.01 to 0.50 :1, For example, the composition
may comprise a sulphate component (for example sodium sulphate) in a weight ratio to PEG of 0.02
to 0.25 : 1, for example 0.03 to 0.22 : 1, for example 0.05 to 0.20 : 1, for example 0.10 to 0.20 : 1.
In an alternative preferred embodiment, the composition does not comprise a sulphate component;
that is to say that the composition is essentially free from alkali metal sulphates and alkaline earth
metal sulphates; in particular essentially free from sodium sulphate, potassium sulphate and
magnesium sulphate.
Preferred flavouring agents are as set out above in section 5a) in relation to solutions of the invention.
For example the composition may comprise a flavouring agent in a weight ratio to PEG of 0.0005 to
0.05 : 1, for example 0.001 to 0.050 : 1, for example 0.003 to 0.030 : 1.
Preferred sweeteners are as set out above in section 5a) in relation to solutions of the invention. For
example the composition may comprise a sweetener in a weight ratio to PEG of 0.0005 to 0.025 : 1,
for example 0.001 to 0.050 : 1, for example 0.01 to 0.035 : 1.
In particular, the invention provides a composition comprising the following components in the
following weight ratios:
a) ascorbate anion: 0.78 to 1.2 parts
b) PEG having an average molecular weight of 3000 to 4000 Da: 1.0 part.
c) sodium chloride and potassium chloride;
d) optionally sodium sulphate;
e) optionally one or more flavouring agents; and
f) optionally one or more sweeteners.
the ascorbate anion being provided by one or more salts of ascorbic acid;
the composition being essentially free from ascorbic acid.
Each of c) and d) may be present in the weight ratios to PEG described above. Each of e) and f) may
be as described above and/or be in the weight ratios to PEG described above.
In one embodiment, the invention provides a composition comprising the following components in
the following weight ratios:
a) sodium ascorbate: 0.90 to 1.125 parts
b) PEG having an average molecular weight of 3000 to 4000 Da: 1 part
c) sodium chloride 0.04 to 0.10 parts and litre potassium chloride 0.02 to 0.04 parts;
e) one or more flavouring agents: 0.001 to 0.075 parts; and
f) one or more sweeteners: 0.002 to 0.050 parts.
For example, the composition may comprise the following components in the following weight ratios:
a) sodium ascorbate: 1.0 parts
b) PEG having an average molecular weight of 3000 to 4000 Da: 1 part
c) sodium chloride 0.0625 parts and litre potassium chloride 0.0225 parts;
e) one or more flavouring agents: 0.001 to 0.075 parts; and
f) one or more sweeteners: 0.002 to 0.050 parts.
For example, the flavouring and sweetener may be 0.020parts orange flavour and 0.0275parts
aspartame. For example, the flavouring and sweetener may be 0.040parts lemon/lime flavour and
0.041parts aspartame. For example, the flavouring and sweetener may be 0.054parts orange flavour
and 0.041parts aspartame.
In an embodiment, the composition consists essentially of those components; that is to say that it does
not contain any further components in significant quantities. The composition may, for example, not
contain any sulphate.
Preferred compositions of the invention are dry compositions, for example dry powder compositions.
f) Methods of preparing solutions and compositions
The invention further provides a method of preparing a solution of the invention comprising
combining the components of the solution with water. The method comprises the step of combining
the components with water and admixing. Some or all of the components may be in physical
association with each other before the water is added. In some embodiments, the components of the
composition are provided in more than one part; that is to say that they are packaged separately. All
of the components may be combined with each other before combining with water. For example, if
flavouring agent and sweetener are packaged separately from other components, they may be
combined with the other components before combining with water. One or some of the components
may be combined with water and admixed in a first step and then or all of the remaining components
may be added in a second step. For example, the components may be in dry form, for example in
powder form.
As set out above in section 5d), the invention provides a composition (for example a dry composition,
for example a powder) for the preparation of a solution of the invention. The invention further
provides a method of preparing a composition of the invention comprising combining the components
of the composition. For example, the method may be a method of preparing a composition of the
invention in powder form. The method may comprise blending a mixture of:
a) ascorbate anion 0.78 to 1.2 parts; and
b) polyethylene glycol 1.0 part;
the ascorbate anion being provided by one or more salts of ascorbic acid;
the composition being essentially free from ascorbic acid
Preferred ascorbate salts are as set out above in section 5a). Preferred ratios of components a) and b)
as as set out above in section 5a). Preferably the ascorbate anion is in a weight ratio to PEG of 0.80 to
1.0 :1. More preferably, the weight ratio is 0.85 to 0.95 : 1, for example 0.86 to 0.90 : 1, for example
0.88:1.
The preferred ascorbate salt is sodium ascorbate. Preferably the sodium ascorbate and PEG are in a
weight ratio of0.90to 1.125 :1. More preferably, the weight ratio is 0.956 to 1.069 : 1,for example
0.968 to 1.013: 1, for example 0.99 :1, for example 1:1.
The method may further comprise blending a mixture of:
a) ascorbate anion: 0.78 to 1.2 parts;
b) polyethylene glycol: 1.0 part;
cl) sodium chloride: 0.005 to 1.0 parts; and
c2) potassium chloride: 0.005 to 1.0 parts;
the ascorbate anion being provided by one or more salts of ascorbic acid;
the composition being essentially free from ascorbic acid.
Preferred ratio amounts of sodium chloride to PEG and potassium chloride to PEG are as set out
above in section 5e).
The components may be weighed out and added together before blending, or the components may be
added into a blend mixture in any desired order.
Blending of the compositions in bulk may, for example, be carried out on a tonne scale. After
blending, the composition is divided into smaller portions for packaging into dosage amounts. The
invention thus provides a method comprising the step of dividing bulk composition as set out in
section 5e) above into smaller portions. The invention also provides a method comprising the step of
filling containers with individual dosage amounts of bulk composition as set out in section 5e). The
invention thus provides a method comprising the step of filling a container with a composition as set
out in section 5d). The composition as set out in section 5d) may be presented in two or more parts.
The method may thus comprise the step of filling a container with some but not all of the components
of a composition as set out in section 5d).
6. Methods of cleansing and solutions for use in them
a) Split-dose colon cleansing treatments
The solutions and compositions of the first and second aspects of the invention set out in sections 2 to
above find particular use in split dose colon cleansing treatments in which the subject takes two
different agents (for example two different solutions): a first colon cleansing agent (for example
solution), followed by a second colon cleansing agent (for example solution). Herein, the "second
colon cleansing agent" means the agent that is taken chronologically second, after the "first colon
cleansing agent". Preferably, the solution of the first or second aspect of the invention is the second
colon cleansing agent. Alternatively, it may be the first agent. The invention thus provides, in a third
aspect a method of cleansing the colon of a mammal comprising:
- the subject taking an effective amount of a first colon cleansing agent; and then
- the subject taking an effective amount of a second colon cleansing agent,
the second colon cleansing agent being a solution of the first or second aspect of the invention
described above. Preferably, the first colon cleansing agent is of different composition from the
second colon cleansing agent. Details of the regimens in which the method may be carried out are
described in further detail in section 3c) above. The first colon cleansing agent may be a colon
cleansing solution. Alternatively, it may be a colon cleansing agent in solid form, for example in the
form of a tablet, for example a PEG-containing tablet, or a bisacodyl-containing tablet. The first
colon cleansing agent may, for example, contain a laxative, for example a stimulant laxative. For
example, bisacodyl, castor oil, senna or bisoxatin may be used.
The invention also provides a method of cleansing the colon of a mammal comprising:
- the subject taking an effective amount of a first colon cleansing agent; and then
- the subject taking an effective amount of a second colon cleansing agent,
the second colon cleansing agent being a 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) optionally 10 to 200 g per litre polyethylene glycol.
The invention also provides a method of cleansing the colon of a mammal comprising:
- the subject taking an effective amount of a first colon cleansing agent; and then
- the subject taking an effective amount of a second colon cleansing agent,
the second colon cleansing agent being a solution comprising
a) 360 to 440 mmol per litre ascorbate anion provided by one or more salts of ascorbic acid; and
b) optionally 10 to 200 g per litre polyethylene glycol;
the solution being essentially free from ascorbic acid.
The method of the invention may be used to cleanse the colon prior to carrying out a diagnostic,
therapeutic or surgical procedure on the colon, rectum or anus or elsewhere in the abdomen. The
diagnostic or surgical procedure may, for example, be colonoscopy, barium enema examination,
sigmoidoscopy or colon surgery. The method of the invention is generally finished less than 8 hours
before carrying out the diagnostic, therapeutic or surgical procedure on the colon, rectum or anus or
elsewhere in the abdomen. Preferably, it is finished less than 4 hours before.
The invention further provides a method of conducting a diagnostic or surgical procedure, for
example, a colonoscopy, barium enema examination, sigmoidoscopy or colon surgery, comprising the
steps of:
a) cleansing the colon by a method of the invention, and then
b) carrying out the diagnostic or surgical procedure.
The invention further provides a first colon cleansing agent, and a second colon cleansing agent, for
use in a method of cleansing the colon comprising:
- the subject taking an effective amount of a first colon cleansing agent;
- the subject taking an effective amount of a second colon cleansing agent,
the second colon cleansing agent being a solution of the first or second aspect of the invention
described above.
The invention further provides a first colon cleansing agent, and a second colon cleansing agent, for
use in a method of cleansing the colon comprising:
- the subject taking an effective amount of a first colon cleansing agent;
- the subject taking an effective amount of a second colon cleansing agent,
the second colon cleansing agent being a solution in water of:
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) optionally 10 to 200 g per litre polyethylene glycol.
In an embodiment, the first agent is different from the second.
The invention further provides a first colon cleansing agent, and a second colon cleansing agent, for
use in a method of cleansing the colon comprising:
- the subject taking an effective amount of a first colon cleansing agent;
- the subject taking an effective amount of a second colon cleansing agent,
the second colon cleansing agent being a solution in water of:
a) 360 to 440 mmol per litre ascorbate anion provided by one or more salts of ascorbic acid; and
b) optionally 10 to 200 g per litre polyethylene glycol.
the solution being essentially free from ascorbic acid.
In an embodiment, the first agent is different from the second. Further details of possible first colon
cleansing agents are provided below in section 6b)
The second colon cleansing agent is preferably as described hereinabove in sections 2 to 5 in relation
to solutions and uses of the first and second aspects of the invention. It is preferably used in a volume
as described hereinabove in relation to solutions and uses of the invention as described hereinabove in
sections 2 to 5.
The first and second colon cleansing agents may be provided in a kit. Further details of such kits are
provided in section 8) below.
b) The "first" colon cleansing agent
The first cleansing agent may be a solution, referred to as the first colon cleansing solution. The first
colon cleansing solution may, for example, be a bowel content suspending agent. The first colon
cleansing solution may comprise polyethylene glycol and/or an alkali metal sulphate, an alkaline earth
metal sulphate or a mixture thereof. The first colon cleansing solution may be hyper-osmotic.
Preferably, the first colon cleansing solution comprises polyethylene glycol (PEG). The polyethylene
glycol (PEG) may have an average molecular weight of 2000 to 8000, for example 2500 to 4500 Da,
for example 2680 to 4020 Da, for example 3000 to 4000 Da. For example, the PEG may be PEG
3350 or PEG 4000 as defined in national pharmacopeias. PEG8000 may also be used. Further
examples of suitable PEGs recognized in some national pharmacopeias include Macrogols, for
example Macrogol 3350 or Macrogol 4000.
Preferably, the first colon cleansing solution comprises 70 to 250 g per litre of PEG. Preferably, the
solution comprises 130 to 250 g per litre PEG, for example 90 to 200g per litre of PEG, more
preferably 100 to 200 g per litre, for example 120 to 150 g per litre, for example 133.3g per litre; for
example 150 to 250 g per litre, for example 175 to 225 g per litre, for example 200g per litre.
Preferably, the first colon cleansing solution comprises one or more alkali metal sulphates, alkaline
earth metal sulphates or a mixture thereof (herein referred to as a "sulphate component"). An alkali
metal or alkaline earth metal sulphate may, for example, be selected from sodium sulphate, potassium
sulphate and magnesium sulphate. The solution may comprise more than one of sodium sulphate,
potassium sulphate and magnesium sulphate, for example all three. Preferably, the sulphate
component is or includes sodium sulphate.
Preferably, the first colon cleansing solution comprises a sulphate component (for example sodium
sulphate) at a concentration of 2 to 20 g per litre, for example 2 to 15 g per litre, for example 5 to 15 g
per litre, for example 8 to 12 g per litre, for example 8 or 12 g per litre; for example 10 to 20 g per
litre, for example 15 to 20 g per litre, for example 17 to 19 g per litre, for example 18g per litre. For
example, the first colon cleansing solution comprises 8.0 to 20 g per litre of one or more alkali metal
sulphates, alkaline earth metal sulphates or a mixture thereof.
Accordingly, the first colon cleansing solution may comprise:
(i) 70 to 250 g per litre PEG having an average molecular weight of 2500 to 4500 Da.
(ii) 2.0 to 20 g per litre of one or more alkali metal sulphates, alkaline earth metal sulphates or a
mixture thereof
(iii) optionally one or more electrolytes;
(iv) optionally one or more flavouring agents; and
(v) optionally one or more sweeteners.
The first colon cleansing solution may comprise one or more electrolytes. Electrolytes include salts
of sodium, potassium, calcium and magnesium, particularly sodium and potassium; and salts of
chloride, iodide, bicarbonate and carbonate, particularly chloride. Preferred electrolytes are sodium
chloride and potassium chloride. In an embodiment, sodium bicarbonate is not included.
For example, the first colon cleansing solution may comprise sodium chloride at a concentration of
0.5 to 5.0 g per litre. For example, sodium chloride may be present at a concentration of 1.0 to 4.0 g
per litre, for example 1.0 to 3.0 g per litre, for example 1.5 to 3.0g per litre, for example 2.0 to 3.0g
per litre; for example 3.0 to 5.0 g per litre, for example 3.5 to 4.5g per litre, for example 4.0 g per
litre.
For example, the first colon cleansing solution may comprise potassium chloride at a concentration of
1 to 10 g per litre. For example, potassium chloride may be present at a concentration of 0.05 to 5.0 g
per litre, for example 0.1 to 3.0g per litre, for example 0.2 to 2.0 g per litre, for example 0.5 to 1.5 g
per litre, for example 0.5 to 1.1 g per litre; for example 1.5 to 2.5 g per litre, for example 1.8 to 2.2 g
per litre, for example 2.0 g per litre.
In an embodiment, the first colon cleansing solution comprises sodium chloride and potassium
chloride. They can be present in the amounts mentioned immediately above. For example, sodium
chloride may be present at a concentration of 1.0 to 3.0g per litre and potassium chloride may be
present at a concentration of 2.5 to 3.0 g per litre; for example, sodium chloride may be present at a
concentration of 3.0 to 5.0g per litre and potassium chloride may be present at a concentration of 0.5
to 1.1 g per litre.
In an embodiment, the first colon cleansing solution comprises sodium chloride and potassium
chloride. They can be present in the amounts mentioned immediately above. For example, sodium
chloride may be present at a concentration of 1.5 to 3.0g per litre and potassium chloride may be
present at a concentration of 0.2 to 2.0 g per litre; for example, sodium chloride may be present at a
concentration of 3.0 to 5.0g per litre and potassium chloride may be present at a concentration of 1.5
to 2.5 g per litre.
For example, 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) optionally one or more flavouring agents; and
(v) optionally one or more sweeteners.
In an embodiment, the first colon cleansing solution may be a solution as commercialised under the
tradename MOVIPREP® or a solution as commercialised under the tradename SUCLEAR®.
The first colon cleansing solution preferably includes a flavouring agent. The first colon cleansing
solution preferably includes a sweetener. Flavouring agents and sweeteners may be as described
hereinabove.
For example, a flavouring for use in in the first colon cleansing solution should preferably mask
saltiness, be relatively sweet but not excessively so, and be stable in the composition. A flavouring
makes the solutions more palatable and thus aids patient compliance. Preferred flavourings include
lemon e.g. Ungerer Lemon (available from Ungerer Limited, Sealand Road, Chester, England CHI
4LP) strawberry e.g. Ungerer Strawberry, grapefruit e.g. Ungerer Grapefruit flavouring powder,
blackcurrant e.g. Ungerer Blackcurrant, pineapple e.g. IFF (International Flavours and Fragrances)
Pineapple flavouring powder, orange eg Firmenich Orange, and vanilla/lemon and lime e.g. IFF
Vanilla and Givaudin Roure Lemon and Lime Flav-o-lok, fruit punch eg Ungerer fruit punch, citrus
punch, mango, and berry. Those and further suitable flavourings are available from International
Flavours and Fragrances Inc. (Duddery Hill, Haverhill, Suffolk, CB9 8LG, England), Ungerer &
Company (Sealand Road, Chester, England CHI 4LP) or Firmenich (Firmenich UK Ltd., Hayes
Road, Southall, Middlesex UB2 5NN). More preferred flavourings are lemon, kiwi, strawberry
grapefruit, fruit punch and mango. Fruit punch and mango are especially preferred flavours.
A particularly preferred flavouring is fruit punch flavour, for example at a level of 0.4 to 3.5g per
litre, for example 0.4 to 1.2g per litre, for example 0.938, 1.0 or 3.18g per litre.
The first cleansing solution preferably includes a sweetener. Preferred sweeteners include aspartame,
acesulfame potassium (acesulfame K), sucralose and saccharine, and/ or combinations thereof. For
example, the solution may comprise one or both of aspartame and acesulfame potassium (acesulfame
K). For example, it may comprise one or both of sucralose and acesulfame potassium (acesulfame K).
In a preferred embodiment, the solution comprises aspartame or sucralose, for example sucralose.
Preferred sweeteners include aspartame, acesulfame potassium (acesulfame K), sucralose and
saccharine, and/ or combinations thereof. For example, compositions of the invention may comprise
one or both of aspartame and acesulfame potassium (acesulfame K). For example, compositions of
the invention may comprise one or both of sucralose and acesulfame potassium (acesulfame K). In a
preferred embodiment, the solution comprises aspartame or sucralose, for example aspartame.
Alternatively, compositions of the invention can be essentially free from added sweeteners, for
example to minimize the number of different components in the compositions.
A souring agent (for example citric acid) may be present as a taste enhancer. A souring agent is a
component that imparts a sourness to a composition. Other souring agents include malic acid, acetic
acid, tartaric acid, gluconodeltalactone, phosphoric acid, succinic acid, phytic acid, lactic acid or salts
thereof. It may be present at a level of from 0.1 to 3.0 g per litre, for example 0.3 to 2.0 g per litre,
for example 0.5 to 2.0g per litre, for example 0.75g, 1.0g, 1.06g, 1.25g or 1.5g per litre. The souring
agent (for example citric acid) may be provided in an encapsulated form. The encapsulation provides
a coating that isolates the souring agent from other components and from air and moisture prior to its
use. Several encapsulated forms of citric acid, or other souring agents, are commercially available.
For example, the encapsulation may be with a water-soluble coating.
The amount of sweetener required depends on the nature and strength of the sweetener being
considered. Typically, it is 0.10 to 4 g per litre. For example, the sweetener may be sucralose at 0.1
to 3.0g per litre, for example 0.3 to 2.0 g per litre, for example 0.5 to 2.0g per litre, for example 0.5 to
1.3g per litre for example 0.63g, 0.80g, 1.0g or 1.58g per litre.
The first cleansing solution may include one or more further optional components. Such components
may be as set out above in section 3b).
In an embodiment, the first colon cleansing solution has a volume of from 400 to 600ml (for example
500ml), and contains the quantities of solutes described in the section immediately above. For
example the volume may be 16 or 17 US fluid ounces. For example, the invention provides colon
cleansing solution comprising :
(i) 175 to 220 g per litre PEG having an average molecular weight of 2500 to 4500 Da.
(ii) 15 to 20 g per litre of one or more alkali metal sulphates, alkaline earth metal sulphates or a
mixture thereof
(iii) 3.0 to 5.0 g per litre sodium chloride, and 1.5 to 2.5 g per litre potassium chloride;
(iv) optionally one or more flavouring agents; and
(v) optionally one or more sweeteners.
Such a solution has a smaller volume than cleansing solutions that are generally used.
In an embodiment, the first colon cleansing solution is provided in a volume of from 300ml up to
1200ml. For example, the first solution may have a volume in a range with a lower limit of 300ml,
400ml, 500ml, 600ml or 700ml. Preferably, the lower limit is 500ml, 600ml or 700ml. The volume
may be in a range with an upper limit of 1200ml, 1100ml, 1000ml, 900ml or 800ml. For example the
volume may be in the range 400ml to 1100ml, for example 500ml to 1000ml, for example 600ml to
900ml, for example 700ml to 800ml. For example, the first colon cleansing solution is provided in a
volume of 750ml. For example the volume may be in the range 400ml to 600ml. For example, the
first colon cleansing solution is provided in a volume of 500ml. For example it may be in a volume of
16 or 17 US fluid ounces. The most appropriate volume will depend on the exact components of the
solution and the amounts in which they are present. In general, for a solution of higher osmotic
strength, a smaller volume will be required.
The first cleansing solution may, for example, have a measured osmolality in the range 200 to 2000
mOsmol/kg, 200 to 1500 mOsmol/kg. In a preferred embodiment, it is hyper-osmotic. It may, for
example have a measured osmolality in the range 320 to 1500 mOsmol. For example, the measured
osmolality of the first cleansing solution is in the range 330 to 1200 mOsmol/kg, for example 340 to
1000 mOsmol/kg, for example 350 to 800 mOsmol/kg, for example 350 to 700 mOsmol/kg. For
example, the solutes in the solution may have a V(350) value of from 800 to 1600ml, for example
from 1000 to 1400ml, for example from 1150 to 1250ml, and be in a volume of 400 to 600ml, for
example 500ml.
The invention further provides a composition optionally presented in two or more parts for the
preparation of a first colon cleansing solution. For example the composition may comprise:
(i) 87.5 to 110 g PEG having an average molecular weight of 2500 to 4500 Da.
(ii) 7.5 to 10 g of one or more alkali metal sulphates, alkaline earth metal sulphates or a mixture
thereof
(iii) 1.5 to 2.5g sodium chloride and 0.75 to 1.25g potassium chloride;
(iv) optionally one or more flavouring agents; and
(v) optionally one or more sweeteners.
For example the composition may comprise:
(i) 100 g PEG having an average molecular weight of 3000 to 4000 Da.
(ii) 9.0 g sodium sulphate
(iii) 2.0g sodium chloride and 1.0g potassium chloride;
(iv) optionally one or more flavouring agents; and
(v) optionally one or more sweeteners.
For example, the flavouring and sweetener may be 0.469g fruit punch flavouring, 0.476g sucralose
and 0.792g citric acid. For example, the flavouring and sweetener may be 0.500g fruit punch
flavouring, 0.40g sucralose and 0.75g citric acid. For example, the flavouring and sweetener may be
1.43g mango flavouring, 0.79g sucralose and 1.74g citric acid. For example, the flavouring and
sweetener may be 1.59g fruit punch flavouring, 0.79g sucralose and 1.74g citric acid. Citric acid may
optionally be packaged separately from the other components.
Particular first solutions SI and S2, and particular second solutions T1 and T2 are described in the
examples section below. In a preferred aspect of the present invention, there is provided a method of
cleansing the colon of a subject comprising (or consisting essentially of):
administering to the subject a cleansing solution of S2 as set forth herein;
administering to the subject a cleansing solution of T1 as set forth herein.
In preferred embodiments of this aspect of the invention, the cleansing solution of S2 is administered
to the subject before the cleansing solution of T1 is administered. It is particularly preferred that S2 is
administered to the subject and then, following a time interval (such as disclosed herein), T1 is
administered to the subject. In further preferred embodiments of this aspect of the invention,
additional fluid (such as clear fluid) is administered to the subject in conjunction with S2 and/or Tl.
For example, additional clear fluid (such as 500ml or thereabout, or 1000ml or thereabout) is
administered to the subject following administration of S2 and/or Tl. Alternatively, additional clear
fluid is administered to the subject during administration of S2 and/or Tl. In typical embodiments,
the cleansing solution of S2 and/or Tl is self-administered.
7. Use of sweetener in colon cleansing solution
It has been found by the current inventors that a sulphate-containing colon cleansing solution that
contains a souring agent (for example citric acid) and sucralose is particularly palatable.
The invention further provides, according to a fourth aspect, a colon cleansing solution comprising:
(i) 70 to 250 g per litre PEG having an average molecular weight of 2500 to 4500 Da;
(ii) 2.0 to 20 g per litre of one or more alkali metal sulphates, alkaline earth metal sulphates or a
mixture thereof;
(iii 1) optionally 1.0 to 5.0 g per litre sodium chloride;
(iii 2) optionally 0.5 to 1.5 (for example 0.5 to 1.1) g per litre potassium chloride;
(iv) optionally one or more flavouring agents;
(v) sucralose; and
(vi) one or more souring agents.
Further, the invention provides a method for improving the palatability of a sulphate-containing colon
cleansing solution comprising including in the solution 0.1 to 3.0g per litre sucralose and 0.1 to 4.0g
per litre of souring agent, for example 0.1 to 3.0 g per litre of souring agent, for example citric acid.
The invention provides a method for diminishing the poor taste of a sulphate-containing colon
cleansing solution comprising including in the solution 0.1 to 3.0g per litre sucralose and 0.1 to 4.0gof
souring agent, for example 0.1 to 3.0 g per litre of souring agent, for example citric acid.
It is postulated that the improved palatability is associated with a reduced perceived saltiness of the
solutions. The invention thus provides a method for reducing the perceived saltiness of a sulphate-
containing colon cleansing solution comprising including in the solution 0.1 to 3.0g per litre sucralose
and 0.1 to 4.0g per litre of souring agent, for example 0.1 to 3.0 g per litre of souring agent, for
"Reduction" here is taken to mean as compared with an equivalent solution
example citric acid.
without the sucralose and souring agent.
A souring agent may be selected from citric acid, malic acid, acetic acid, tartaric acid,
gluconodeltalactone, phosphoric acid, succinic acid, phytic acid, lactic acid or salts thereof. For
example, the souring agent may be citric acid. It may be present at a level of from 0.1 to 4.0g per
litre, for example 0.1 to 3.0 g per litre, for example 0.3 to 2.0 g per litre, for example 0.5 to 2.0g per
litre, for example 0.75g, 1.0g, 1.06g, 1.25g or 1.5g per litre. For example, it may be at a level of 3.0
to 4.0g per litre, for example 3.48g per litre. Citric acid, or another souring agent, may be provided in
an encapsulated form. The encapsulation provides a coating that isolates the souring agent from other
components and from air and moisture prior to its use. Several encapsulated forms of citric acid, or
other souring agents, are commercially available. For example, the encapsulation may be with a
water-soluble coating.
The sucralose may, for example be present at a level of 0.1 to 3.0g per litre, for example 0.3 to 2.0 g
per litre, for example 0.5 to 2.0g per litre, for example 0.5 to 1.3g per litre for example 0.63g, 0.80g,
or 1.0g per litre. For example, it may be at a level of 1.58g per litre.
When sucralose and citric acid are used, a particularly preferred flavouring is fruit punch flavour, for
example at a level of 0.4 to 1.2g per litre, for example 0.625g per litre or 1.0g per litre.
There is also provided a composition for the preparation of such a solution, for example by admixture
with water. Preferred amounts of each of components (i) to (iv) in the solutions and compositions of
the fourth aspect of the invention are as set out for the first colon cleansing solutions and first colon
cleansing compositions hereinabove in section 6b).
A colon cleansing solution according to the fourth aspect of the invention may contain PEG, sulphate,
sodium chloride, potassium chloride and flavouring in amounts and types as described hereinabove in
relation to the first colon cleansing solution in section 6b).
A colon cleansing solution according to the fourth aspect of the invention may be used together with a
solution of the first or second aspect of the invention as set out in sections 2 to 5. Alternatively, it
may be used in combination with a different other colon cleansing solution, or used in a suitable
volume on its own. If used on its own, it may be used in a single dose or in a split dose
administration. The invention provides a method of cleansing the colon of a subject comprising
administering a solution of the fourth aspect of the invention. The solution may be administered on
its own or in combination with a further, different, solution.
8. Kits
a) kits providing a composition for the preparation of a solution of the invention
As set out above in section 2d), the invention provides a composition for admixture with water (for
example a dry composition, for example a powder), wherein the composition is optionally presented
in two or more parts and comprises the components of a solution of the invention. If the components
are provided in two or more parts, they may be provided in a kit. The invention thus provides a kit
comprising:
a) 150 to 400 mmol 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) 5 to 100 g polyethylene glycol.
The kit may further comprise additional components as set out in sections 3a), 3b) and 3d) above, and
in the amounts set out there. For example, the kit may contain:
a) 150 to 400 mmol 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;
b) 5 to 100 g PEG having an average molecular weight of 3000 to 4000 Da.
c) sodium chloride and potassium chloride;
d) optionally sodium sulphate;
e) optionally one or more flavouring agents;
f) optionally one or more sweeteners.
Each of c) and d) may be present in the amounts described in section 3a) and 3d) above. Each of e)
and f) may be as described above and/or be in the amounts described in section 3a) and 3d) above.
In one embodiment, the kit contains:
(i) 6.0 to 10g ascorbic acid and
(ii) 40 to 60g sodium ascorbate
the components (i) and (ii) being present in a weight ratio of from 1:5063 to 1:7.875;
b) 30 to 50g PEG having an average molecular weight of 3000 to 4000 Da;
c) 1.5 to 4g sodium chloride and 0.5 to 3.5g potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners.
In an embodiment of a kit of the invention, the ascorbate component a) is packaged separately from
the PEG component b). The remaining elements may be packaged together with the PEG component.
In an embodiment of a kit of the invention, the flavouring component e) or the sweetener component
f) may be provided separately from other components. The kit may provide several alternative
flavourings, allowing the subject to decide themselves which flavouring from a range of flavourings
to use.
For example, the kit may contain:
(i) 7.54g ascorbic acid and
(ii) 48.1 lg sodium ascorbate
b) 40g PEG having an average molecular weight of 3000 to 4000 Da;
c) 3.20g sodium chloride and 1.20g potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners;
whereby component a) is packaged in a first compartment and components b), c) e) and f) are
packaged in a second compartment.
One or more of the components may be in a dry powder form (for example the ascorbate component
or the PEG component may be in dry powder form), whilst some of the remaining components (for
example the sodium chloride or the potassium chloride) are in the form of a tablet or in a semi-solid
(for example gel) form. In such an embodiment, the subject may be instructed to dissolve the powder
components in water and drink it, and instructed to take the tablet or semi-solid form without
dissolution.
If a semi-solid form (for example gel) is present, the subject may be instructed to add it
to water before ingesting it, or the subject may be instructed to take it as provided.
As set out above in section 5d), the invention provides a composition for admixture with water (for
example a dry composition, for example a powder), wherein the composition is optionally presented
in two or more parts and comprises the components of a solution of the invention. If the components
are provided in two or more parts, they may be provided in a kit. The invention thus provides a kit
comprising:
a) 180 to 220 mmol ascorbate anion provided by one or more salts of ascorbic acid; and
b) 5 to 100 g polyethylene glycol;
the kit being essentially free from ascorbic acid.
The kit may further comprise additional components as set out in sections 5a), 5b) and 5d) above, and
in the amounts set out there. For example, the kit may contain:
a) 180 to 220 mmol ascorbate anion provided by one or more salts of ascorbic acid;
b) 5 to 100 g PEG having an average molecular weight of 3000 to 4000 Da.
c) sodium chloride and potassium chloride;
d) optionally sodium sulphate;
e) optionally one or more flavouring agents;
f) optionally one or more sweeteners;
the kit being essentially free from ascorbic acid.
Each of c) and d) may be present in the amounts described in section 5a) and 5d) above. Each of e)
and f) may be as described above and/or be in the amounts described in section 5a) and 5d) above.
In one embodiment, the kit contains:
a) 35.65 to 43.55g sodium ascorbate
b) 30 to 50g PEG having an average molecular weight of 3000 to 4000 Da;
c) 1.5 to 4g sodium chloride and 0.5 to 3.5g potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners;
the kit being essentially free from ascorbic acid.
In an embodiment of a kit of the invention, the ascorbate component a) is packaged separately from
the PEG component b). The remaining components may be packaged together with the PEG
component.
In an embodiment of a kit of the invention, the flavouring component e) or the sweetener component
f) may be provided separately from other components. The kit may provide several alternative
flavourings, allowing the subject to decide themselves which flavouring from a range of flavourings
to use.
For example, the kit may contain:
a) 40g sodium ascorbate
b) 40g PEG having an average molecular weight of 3000 to 4000 Da;
c) 2.50g sodium chloride and 0.90g potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners;
whereby component a) is packaged in a first compartment and components b), c) e) and f) are
packaged in a second compartment.
In a further embodiment, one or more of the components may be in a dry powder form (for example
the ascorbate component or the PEG component may be in dry powder form), whilst some of the
remaining components (for example the sodium chloride or the potassium chloride) are in the form of
a tablet or in a semi-solid (for example gel) form. In such an embodiment, the subject may be
instructed to dissolve the powder components in water and drink it, and instructed to take the tablet or
semi-solid form without dissolution. If a semi-solid form (for example gel) is present, the subject
may be instructed to add it to water before ingesting it, or the subject may be instructed to take it as
provided.
It is convenient for the patient for a kit of the invention to be provided in the form of, for example, a
box. The kit may be provided in a package, or example an envelope (which may be addressed to the
subject), for example a padded envelope. The box or other package containing the kit may, for
example, be one that can be posted into a standard domestic mailbox, so that it can conveniently be
sent to a subject in the mail. In the USA, that typically means that a box fits into a slot 1.75 inches
high by 10 inches wide. In Europe, the minimum mailbox aperture width is generally 230mm and the
minimum height is 30mm. In a kit of the invention the first and/or second parts may each contained
in one or more containers. Examples of suitable containers include tubs, bags and sachets. A
preferred container is a sachet.
In one embodiment, the composition of the invention can be provided in a multi-chambered container,
for example of the type disclosed in WO2012/105524. A multi-chambered container may have a
partition wall and two separate powders can be stored separated from each other. In addition, in a
container of the type disclosed in WO2012/105524, a powdered medicine, which has been stored in a
separated state, can be simply and readily mixed at the time of use to provide an aqueous solution.
For example, a multi-chambered container comprises a substantially flat pouch formed from a flexible
film, a partition wall configured as a detachable seal detachably welding opposing inner surfaces of
the pouch, and a pour port for infusion and discharge of a liquid, that is attached to the periphery of
the pouch so as to open into one of the plurality of partitioned chambers. For example, the partition
wall comprises a horizontal section which extends along a gusseted bottom section of the pouch and a
perpendicular section which is curved from the horizontal section to a pouch upper section. The
partition wall may, for example, be frangible. For example, a first partitioned chamber having a large
capacity is formed on one side of the partition wall close to the bottom section of the pouch, a second
partitioned chamber having a small capacity is formed on the other side of the partition wall, and the
pour port opens into the first partitioned chamber.
b) kits providing treatments according to the invention
As set out above in section 6), the invention provides various split-dose treatments for colon cleansing
in which the subject takes two different agents. The invention thus provides a kit comprising:
- a first colon cleansing agent, and
- a second colon cleansing agent,
the second colon cleansing agent being a solution of the first or second aspect of the invention
described above.
The invention provides a kit comprising:
- a first colon cleansing agent, and
- a second colon cleansing agent,
the second colon agent solution being a solution in water of:
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) optionally 10 to 200 g per litre polyethylene glycol.
The invention also provides a kit comprising:
- a first colon cleansing agent, and
- a second colon cleansing agent,
the second colon cleansing agent being a solution in water of:
a) 360 to 440 mmol per litre ascorbate anion provided by one or more salts of ascorbic acid; and
b) optionally 10 to 200 g per litre polyethylene glycol;
the solution being essentially free from ascorbic acid.
In an embodiment, the first agent is different from the second.
A kit of the invention may provide compositions for the preparation of the colon cleansing solutions.
The invention thus further provides a kit comprising:
A) a first component, being a composition, optionally presented in two or more parts for the
preparation of a first colon cleansing solution as described above by admixture with water; and
B) a second component, being a composition, optionally presented in two or more parts for the
preparation of a second colon cleansing solution by admixture with water, the second colon cleansing
solution being a solution as described hereinabove in relation to solutions and uses of the first or
second aspects of the invention as set out in sections 2 to 5.
Preferably, the first solution is of different composition from the second.
Accordingly, a kit of the invention may comprise:
A) a first component, being a composition optionally presented in two or more parts for the
preparation of a first colon cleansing solution comprising :
(i) 52.5 to 187.5 g PEG having an average molecular weight of 2500 to 4500 Da.
(ii) 1.5 to 15 g of one or more alkali metal sulphates, alkaline earth metal sulphates or a mixture
thereof
(iii) optionally one or more electrolytes;
(iv) optionally one or more flavouring agents; and
(v) optionally one or more sweeteners,
B) a second component, being a composition optionally presented in two or more parts for the
preparation of a second colon cleansing solution, comprising
a) 150 to 400 mmol 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) optionally 5 to 100 g polyethylene glycol,
the first solution being different from the second.
A kit of the invention may comprise:
A) a first component, being a composition optionally presented in two or more parts for the
preparation of a first colon cleansing solution comprising :
(i) 52.5 to 187.5 g PEG having an average molecular weight of 2500 to 4500 Da.
(ii) 1.5 to 15 g of one or more alkali metal sulphates, alkaline earth metal sulphates or a mixture
thereof
(iii) optionally one or more electrolytes;
(iv) optionally one or more flavouring agents; and
(v) optionally one or more sweeteners,
B) a second component, being a composition optionally presented in two or more parts for the
preparation of a second colon cleansing solution, comprising
a) 360 to 440 mmol ascorbate anion provided one or more salts of ascorbic acid; and
b) optionally 5 to 100 g polyethylene glycol,
the solution being essentially free from ascorbic acid;
the first solution being different from the second.
The first component may be a composition for the preparation of a solution as set out in section 6b)
above. The first component preferably comprises 97.5 to 187.5 g of PEG, for example 67.5 to 150 g
of PEG, more preferably 75 to 150 g, for example 90 to 112.5 g, for example 100 g PEG.
Preferably, the first component comprises a sulphate component (for example sodium sulphate) in an
amount of 1.5 to 11.25 g, for example 3.75 to 11.25 g, for example 6 to 9 g, for example 6 or 9 g. For
example, the first component comprises 6.0 to 15 g of one or more alkali metal sulphates, alkaline
earth metal sulphates or a mixture thereof. For example it comprises 9g of sodium sulphate.
Preferably, the first component comprises sodium chloride in an amount of 0.375 to 3.75 g. For
example, sodium chloride may be present in an amount of 0.75 to 3.0 g, for example 0.75 to 2.25 g,
for example 1.125 to 2.25 g, for example 1.5 to 2.25 g, for example 2.0g.
For example, the first component comprises potassium chloride in an amount of 0.75 to 7.5 g. For
example, potassium chloride may be present in an amount of 0.0375 to 3.75 g, for example 0.075 to
2.25 g, for example 0.15 to 1.5 g, for example 0.375 to 1.125 g, for example 0.375 to 0.825 g, for
example 1.0g.
In an embodiment, the first component comprises sodium chloride and potassium chloride. They can
be present in the amounts mentioned immediately above. For example, sodium chloride may be
present in an amount of 1.125 to 2.25 g and potassium chloride may be present in an amount of 0.15
to 1.5 g; for example 2.0g sodium chloride and 1.0g potassium chloride.
The second component of the kit of compositions of the invention is preferably a composition for the
preparation of a solution of the first or second aspect of the invention as described hereinabove in
sections 3 or 5.
Accordingly, the kit may comprise:
A) a first component, being a composition optionally presented in two or more parts for the
preparation of a first colon cleansing solution comprising :
(i) 87.5 to 110 g PEG having an average molecular weight of 2500 to 4500 Da.
(ii) 7.5 to 10 g of one or more alkali metal sulphates, alkaline earth metal sulphates or a mixture
thereof
(iii) 1.5 to 2.5g sodium chloride and 0.75 to 1.25g potassium chloride;
(iv) optionally one or more flavouring agents; and
(v) optionally one or more sweeteners,
B) a second component, being a composition optionally presented in two or more parts for the
preparation of a second colon cleansing solution, comprising
(i) 6.0 to 10g ascorbic acid and
(ii) 40 to 60g sodium ascorbate
the components (i) and (ii) being present in a weight ratio of from 1:5063 to 1:7.875;
b) 30 to 50g PEG having an average molecular weight of 3000 to 4000 Da;
c) 1.5 to 4g sodium chloride and 0.5 to 3.5g potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners.
In an embodiment of a kit of the invention, in component B) the ascorbate component a) is packaged
separately from the PEG component b). The remaining elements of component B) may be packaged
together with the PEG component.
For example, a kit may comprise:
A) a first component, being a composition optionally presented in two or more parts for the
preparation of a first colon cleansing solution comprising :
(i) 100 g PEG having an average molecular weight of 3000 to 4000 Da.
(ii) 9.0 g sodium sulphate
(iii) 2.0g sodium chloride and 1.0g potassium chloride;
(iv) optionally one or more flavouring agents; and
optionally one or more sweeteners,
B) a second component for the preparation of a second colon cleansing solution, comprising
(i) 7.54g ascorbic acid and
(ii) 48.1 lg sodium ascorbate
b) 40g PEG having an average molecular weight of 3000 to 4000 Da;
c) 3.20g sodium chloride and 1.20g potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners;
whereby component a) is packaged in a first compartment and components b), c) e) and f) are
packaged in a second compartment.
For example, the flavouring and sweetener in the first component may be 0.469g fruit punch
flavouring, 0.476g sucralose and 0.792g citric acid. For example, the flavouring and sweetener may
be 0.500g fruit punch flavouring, 0.40g sucralose and 0.75g citric acid. For example, the flavouring
and sweetener may be 1.43g mango flavouring, 0.79g sucralose and 1.74g citric acid. For example,
the flavouring and sweetener may be 1.59g fruit punch flavouring, 0.79g sucralose and 1.74g citric
acid. Citric acid may optionally be packaged separately from the other components.
For example, the flavouring and sweetener in the second component may be 0.60g orange flavour and
1.93g aspartame. For example, the flavouring and sweetener may be 1.60g citrus flavour and 0.875g
aspartame. For example, the flavouring and sweetener may be 2.10g orange grapefruit flavour and
0.875g aspartame.
Alternatively, the kit may comprise:
A) a first component, being a composition optionally presented in two or more parts for the
preparation of a first colon cleansing solution comprising :
(i) 87.5 to 110 g PEG having an average molecular weight of 2500 to 4500 Da.
(ii) 7.5 to 10 g of one or more alkali metal sulphates, alkaline earth metal sulphates or a mixture
thereof
(iii) 1.5 to 2.5g sodium chloride and 0.75 to 1.25g potassium chloride;
(iv) optionally one or more flavouring agents; and
(v) optionally one or more sweeteners,
B) a second component, being a composition optionally presented in two or more parts for the
preparation of a second colon cleansing solution, comprising
a) 35.65 to 43.55g sodium ascorbate
b) 30 to 50g PEG having an average molecular weight of 3000 to 4000 Da;
c) 1.5 to 4g sodium chloride and 0.5 to 3.5g potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners.
In an embodiment of a kit of the invention, in component B) the ascorbate component a) is packaged
separately from the PEG component b). The remaining elements of component B) may be packaged
together with the PEG component.
For example, a kit may comprise:
A) a first component, being a composition optionally presented in two or more parts for the
preparation of a first colon cleansing solution comprising :
(i) 100 g PEG having an average molecular weight of 3000 to 4000 Da.
(ii) 9.0 g sodium sulphate
(iii) 2.0g sodium chloride and 1.0g potassium chloride;
(iv) optionally one or more flavouring agents; and
(v) optionally one or more sweeteners,
B) a second component for the preparation of a second colon cleansing solution, comprising
a) 40g sodium ascorbate
b) 40g PEG having an average molecular weight of 3000 to 4000 Da;
c) 2.50g sodium chloride and 0.90g potassium chloride;
e) one or more flavouring agents; and
f) one or more sweeteners;
whereby component a) is packaged in a first compartment and components b), c) e) and f) are
packaged in a second compartment.
For example, the flavouring and sweetener in the first component may be 0.469g fruit punch
flavouring, 0.476g sucralose and 0.792g citric acid. For example, the flavouring and sweetener may
be 0.500g fruit punch flavouring, 0.40g sucralose and 0.75g citric acid. For example, the flavouring
and sweetener may be 1.43g mango flavouring, 0.79g sucralose and 1.74g citric acid. For example,
the flavouring and sweetener may be 1.59g fruit punch flavouring, 0.79g sucralose and 1.74g citric
acid. Citric acid may optionally be packaged separately from the other components.
For example, the flavouring and sweetener in the second component may be 0.80g orange flavour and
1.1 Og aspartame. For example, the flavouring and sweetener may be 1.60g lemon/lime flavour and
1.625g aspartame. For example, the flavouring and sweetener may be 2.15g orange grapefruit flavour
and 1.625g aspartame.
Preferably, the kit further comprises instructions for use. In an embodiment, a kit of the invention has
instructions that instruct the user of the volume to which each component is to be made up with water.
For example, the specified volume of water for each solution is less than one litre. For example, the
specified volume for the first component may be 300ml to 1200ml, for example 600ml to 900ml, for
example 750ml; for example it may be a volume of 25 or 26 US fluid ounces, for example 400 to
600ml, for example 500ml. For example it may be a volume of 16 or 17 US fluid ounces. For
example, the specified volume for the second component may be from 250ml to 1000ml, for example
400ml to 700ml, for example 500ml. For example it may be a volume of 16 or 17 US fluid ounces.
Further volumes that may be specified in the instructions are the volumes set out hereinabove in
relation to the methods of the invention.
In general, the instructions specify that the first and second solutions are to be ingested in succession
with a time interval between them. In an embodiment, the instructions specify that the first cleansing
solution is ingested first followed, after a time interval (for example the time between an evening and
the following morning) by ingestion of the second cleansing solution. The time interval is preferably
as described above in relation to the methods of the invention. The instructions may specify that the
components in the kit be made up into solutions and then taken in accordance with the description set
out above in section 6 for the first solution and sections 3c) and 5c) for the second solution.
For example, components A) and B) may be in dry powder, granular or other dry form. They may
alternatively be in the form of concentrates or slurries. Components A) and B) may be in the same or
different physical forms. Components within A) and B) may be in the same or different physical
forms. For example, one or both of components A) and B) are dry powders. A portion of either or
each of components A) and B) may be in the form of one or more solid tablets or capsules.
It is convenient for the patient for a kit of the invention to be provided in the form of, for example, a
box. In a kit of the invention the first and/or second components may each contained in one or more
containers. In particular, the second component may be contained in more than one container. For
example, if the second component comprises both ascorbic acid and PEG then the ascorbic acid and
PEG may be contained in separate containers. The other constituents of the second component (for
example one or more of sodium chloride, potassium chloride and sodium sulphate) may be in either of
the separate containers. For example, they may be in the container containing the PEG.
If a flavouring component is present in the first or second solution, then in a kit of the invention, the
flavouring component for the relevant solution may be provided in a separate container from the other
constituents of that solution.
Examples of suitable containers include tubs, bags and sachets. A preferred container is a sachet.
In one embodiment, the composition of the invention can be provided in a multi-chambered container,
for example of the type disclosed in WO2012/105524, as described above in section 8a).
In one embodiment, a kit comprises:
A) a first sachet comprising a first composition for the preparation of the first cleansing solution;
Bl) a second sachet;
B2) a third sachet;
wherein the second and third sachets together provide a composition for the preparation of the second
cleansing solution.
For example, in a kit of the invention as mentioned immediately above:
A) the first sachet comprises polyethylene glycol and/or sodium sulphate;
Bl) the second sachet comprises one or more components selected from polyethylene glycol, one or
more alkali metal sulphates, alkaline earth metal sulphates or a mixture thereof and electrolytes; and
B2) the third sachet comprises one or more salts of ascorbic acid and, if appropriate, ascorbic acid;
the contents of sachets (Bl) and (B2) together providing the components for the second cleansing
solution.
For example, in a further embodiment of a kit of the invention, rather than being provided within a
first sachet (A) with the PEG, some or all of the sulphate(s), electrolytes, flavouring agents and
sweeteners are provided in the form of a tablet or capsule. In a further embodiment of a kit of the
invention, rather than being provided within a second or third sachet (B1 or B2) with the PEG,
ascorbic acid or ascorbate component, some or all of the sulphate(s), electrolytes, flavouring agents
and sweeteners are provided in the form of a tablet or capsule.
A kit may contain one treatment, for example a cleansing treatment, or several treatments. A
treatment generally comprises one dose of the first cleansing solution (or components for preparing
the first cleansing solution) and one dose of the second cleansing solution (or components for
preparing the first cleansing solution). In a kit of the invention, preferably the first component
comprises one dose of the first cleansing solution, and the second component comprises one dose of
the second cleansing solution.
A kit of the invention may be for use in a method of cleansing the colon comprising:
- the subject taking an effective amount of a first colon cleansing solution as described herein; and
- the subject taking an effective amount of a second colon cleansing solution as described herein.
9. Alternative colon cleansing regimens
a) general
The solutions and compositions of the first and second aspects of the invention described above in
sections 2 to 5 find further use in split dose colon cleansing treatments in which the subject takes two
different solutions (a first colon cleansing solution, followed by a second colon cleansing solution) in
which the solution of the first or second aspect of the invention is the first colon cleansing solution.
In a fifth aspect, the invention thus provides a method of cleansing the colon of a mammal
comprising:
- the subject taking an effective amount of a first colon cleansing solution; and then
- the subject taking an effective amount of a second colon cleansing solution,
the first colon cleansing solution being a solution of the first or second aspect of the invention
described above in sections 2 to 5.
The invention also provides a method of cleansing the colon of a mammal comprising:
- the subject taking an effective amount of a first colon cleansing solution; and then
- the subject taking an effective amount of a second colon cleansing solution,
the first colon cleansing solution being a 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) optionally 10 to 200 g per litre polyethylene glycol.
The invention also provides a method of cleansing the colon of a mammal comprising:
- the subject taking an effective amount of a first colon cleansing solution; and then
- the subject taking an effective amount of a second colon cleansing solution,
the first colon cleansing solution being a solution comprising
a) 360 to 440 mmol per litre ascorbate anion provided by one or more salts of ascorbic acid; and
b) optionally 10 to 200 g per litre polyethylene glycol;
the solution being essentially free from ascorbic acid.
The solutions and methods of the fifth aspect of the invention may have the features described above
in relation to the solutions and methods of the third aspect of the invention as set out in section 6
above.
b) alternative:
The invention also provides a method of cleansing the colon of a subject comprising:
- administering to the subject an effective amount of a first cleansing solution; and then after a
time interval
- administering to the subject an effective amount of a second cleansing solution,
wherein the first cleansing solution is hyper-osmotic and contains ascorbic acid, one or more salts of
ascorbic acid, or a mixture thereof (for example ascorbic acid and sodium ascorbate, for example
sodium ascorbate); and wherein the second cleansing solution is either substantially free from
ascorbic acid and salts thereof, or contains ascorbic acid, one or more salts of ascorbic acid, or a
mixture thereof, in an amount providing a lower concentration of ascorbate anion than is present in
the first cleansing solution. The first cleansing solution may comprise PEG and electrolytes (for
example sodium chloride and potassium chloride). The second solution may comprise PEG; it may
comprise an alkali metal or alkaline earth metal sulphate (for example sodium sulphate); it may
comprise electrolytes (for example sodium chloride and potassium chloride). There are also provided
kits comprising a first and a second solution according to the invention, and kits comprising
compositions for preparing the first and second solutions.
The first cleansing solution contains a higher concentration of ascorbate anion than is present in the
second cleansing solution. For example, the first cleansing solution contains twice the concentration
of the ascorbate anion than the second cleansing solution or more. For example, the first solution
contains three times or more, four times or more, or five times or more the concentration of the
ascorbate anion than the second cleansing solution. For example, the first cleansing solution contains
a concentration of the ascorbate anion that is at least 50mmol per litre greater than that of the second
cleansing solution. That is to say that the first solution contains a concentration of ascorbate anion
that is at least 50mmol per litre greater than that of the second solution. For example, the first
solution contains a concentration of the ascorbate anion that is greater by at least 1 OOmmol per litre,
for example at least 200mmol per litre, at least 3 OOmmol per litre.
For example, the second cleansing solution may be substantially free from an ascorbate component.
For example, the first cleansing solution may comprise:
- 56.6g sodium ascorbate, or
- 33.9g sodium ascorbate and 20.Ig ascorbic acid, or
- 33.9g sodium ascorbate, or
- 33.9g sodium ascorbate and 21.4 g magnesium ascorbate.
The first cleansing solution may further comprise polyethylene glycol. The polyethylene glycol
(PEG) may, for example, have an average molecular weight of 2500 to 4500 Da, for example 3000 to
4000 Da. For example, the PEG may be PEG 3350 or PEG 4000 as defined in national
pharmacopeias. Further examples of suitable PEGs recognized in some national pharmacopeias
include Macrogols, for example Macrogol 4000.
For example, the first cleansing solution may comprise 20g or 40g PEG 3350. For example, the first
cleansing solution may have a volume of 500ml. For example it may have a volume of 16 or 17 US
fluid ounces.
The second cleansing solution may comprise polyethylene glycol and/or an alkali metal sulphate, an
alkaline earth metal sulphate, or a mixture thereof.
The polyethylene glycol (PEG) in the second cleansing solution may be as described immediately
above for the first cleansing solution. The PEG in the second cleansing solution can be a different
PEG from the PEG in the second cleansing solution. For example, one PEG may be PEG3350 and
the other PEG may be PEG4000. For example, the second cleansing solution may comprise 100g
PEG 3350. For example, the second cleansing solution may have a volume of 750ml. For example
it may have a volume of 25 or 26 US fluid ounces.
The second cleansing solution preferably comprises an alkali metal sulphate, an alkaline earth metal
sulphate or a mixture thereof. An alkali metal or alkaline earth metal sulphate may, for example, be
selected from sodium sulphate, potassium sulphate and magnesium sulphate. The solution may
comprise more than one of sodium sulphate, potassium sulphate and magnesium sulphate, for
example all three. Preferably, the alkali metal sulphate, an alkaline earth metal sulphate or the
mixture thereof is or includes sodium sulphate. Preferably, an alkali metal sulphate or alkaline earth
metal sulphate (for example sodium sulphate) is anhydrous.
For example, the second cleansing solution may have a volume of 750ml and comprise 3g, 6g or 9g of
sodium sulphate.
The first and/or second cleansing solution(s) may further comprise one or more of:
a) one or more electrolytes;
b) one or more flavouring agents;
c) one or more sweeteners.
Electrolytes include salts of sodium, potassium, calcium and magnesium, particularly sodium and
potassium; and salts of chloride, iodide, bicarbonate and carbonate, particularly chloride. Preferred
electrolytes are sodium chloride and potassium chloride. In an embodiment, the first and/or second
solution is substantially free from sodium bicarbonate.
For example, the second cleansing solution may have a volume of 750ml and comprise 1.4g sodium
chloride and 0.3g potassium chloride; or 1.6g sodium chloride and 0.7g potassium chloride; or 2.0g
sodium chloride and 1.0g potassium chloride.
For example, the first cleansing solution may have a volume of 500ml and comprise 3.5g sodium
chloride and 2.2g potassium chloride; or 2.7g sodium chloride and 1.3g potassium chloride; or 2.8g
sodium chloride and 1.3g potassium chloride; or 2.8g sodium chloride and 2.0g potassium chloride; or
3.1 g sodium chloride and 1.3g potassium chloride. For example the first cleansing solution is
substantially free from sodium bicarbonate.
The first and/or second cleansing solution(s) preferably include a flavouring agent. Flavouring for use
in compositions of the invention should preferably mask saltiness, be relatively sweet but not
excessively so, and be stable in the composition. Flavouring makes the solutions more palatable and
thus aids patient compliance. Preferred flavourings include lemon e.g. Ungerer Lemon (available
from Ungerer Limited, Sealand Road, Chester, England CHI 4LP) strawberry e.g. Ungerer
Strawberry, grapefruit e.g. Ungerer Grapefruit flavouring powder, blackcurrant e.g. Ungerer
Blackcurrant, pineapple e.g. IFF (International Flavours and Fragrances) Pineapple flavouring
powder, orange eg Firmenich Orange, vanilla/lemon and lime e.g. IFF Vanilla and Givaudin Roure
Lemon and Lime Flav-o-lok, fruit punch eg Ungerer fruit punch, citrus punch, mango, and berry.
Those and further suitable flavourings are available from International Flavours and Fragrances Inc.
(Duddery Hill, Haverhill, Suffolk, CB9 8LG, England), Ungerer & Company (Sealand Road, Chester,
England CHI 4LP) or Firmenich (Firmenich UK Ltd., Hayes Road, Southall, Middlesex UB2 5NN).
More preferred flavourings are lemon, kiwi, strawberry, grapefruit, orange, fruit punch and mango.
Fruit punch and mango are especially preferred flavourings for the first solution. The most preferred
flavourings for the second solution are lemon flavour and orange flavour.
The first and/or second cleansing solution(s) preferably include a sweetener. Sugar-based sweeteners
are generally not suited for colon cleansing compositions because the delivery of unabsorbed sugars
to the colon provides a substrate for bacteria. Such sugars may be metabolised by the bacteria to form
explosive gases such as hydrogen and methane. The presence of explosive gases in the colon can be
highly dangerous when electrical apparatus is to be used during colonoscopy or other procedures.
Preferred sweeteners include aspartame, acesulfame potassium (acesulfame K), sucralose and
saccharine, and/ or combinations thereof. For example, compositions of the invention may comprise
one or both of aspartame and acesulfame potassium (acesulfame K). For example, compositions of
the invention may comprise one or both of sucralose and acesulfame potassium (acesulfame K).
Alternatively, compositions of the invention can be substantially free from added sweeteners, for
example to minimize the number of different components in the compositions. Citric acid may also
be present as a taste enhancer.
Examples
General description of sample evaluation protocol
The same sample evaluation protocol was used for the taste tests of all of the solutions described
below that were taste tested. The protocol was as follows:
1. The solution was sipped from 1 oz cups, swished in the mouth, and expectorated.
2. Initial flavour was immediately evaluated (t=0).
3. The aftertaste was evaluated at periodic time intervals: 1, 3 and 5 minutes.
4. Upon completing the evaluation, the panellists cleansed their palates using spring water and
unsalted crackers.
The Panelists were asked to provide a score of their perception of the intensity of the saltiness of the
solutions, using the scale:
0 = None
Intensity Scale:
1 = Slight
2 = Moderate
3 = Strong
In general the panel consisted of from 2 to 8 tasters. The average saltiness intensity score was plotted
against time.
Example 1: Sodium ascorbate/Ascorbic acid solutions
In an initial set of solutions containing PEG3350 (40g), sodium chloride (2.8g), potassium chloride
(1.3g) and sodium ascorbate (56.6g), it was found that the sweeteners sucralose and aspartame were
most effective in reducing the perceived saltiness of the solution. Acesulfame-K and sodium
saccharin were less effective.
The solutions in Tables 1 and 2 were prepared and taste tested. The results of the taste testing are
shown in Figures 1 and 2.
Table 1: Aspartame-containing solutions
PEG3350 NaCl KCl Aspartame Sodium Ascorbic Molar Water
Sol'n
Ascorbate Acid / g ratio to Vol
/g /g /g /g
40 2.8 1.3 0 56.60 0 100:0 500
40 2.8 1.3 2.0 56.60 0 100:0 500
40 2.8 1.3 2.0 39.62 15.10 70:30 500
40 2.8 1.3 2.0 45.28 10.06 80:20 500
40 2.8 1.3 2.0 48.11 7.55 85:15 500
40 2.8 1.3 2.0 50.94 5.03 90:10 500
Table 2: Sucralose-containing solutions
Molar Water
Sol'n PEG3350 NaCl KCl Sucralose Sodium Ascorbic
ratio to Vol
/g /g /g /g Ascorbate Acid / g
/g /ml
56.60 0 100:0 500
Gl 40 2.8 1.3 0
40 2.8 1.3 1.5 56.60 0 100:0 500
39.62 15.10 70:30 500
G3 40 2.8 1.3 1.5
45.28 10.06 80:20 500
G4 40 2.8 1.3 1.5
48.11 7.55 85:15 500
G5 40 2.8 1.3 1.5
50.94 5.03 90:10 500
G6 40 2.8 1.3 1.5
In Figures 1 and 2, it is seen that the saltiness intensity is reduced most in the solution containing
sodium ascorbate and ascorbic acid in the ratio 85:15, ie solutions F5 and G5.
Example 2: Sodium ascorbate solutions and taste testing
The solutions in Table 3 were prepared and taste tested. The results of the taste testing are shown in
Figure 3.
Table 3: Sodium ascorbate solutions
Water to
Sol'n PEG3350 /g NaCl /g KCl /g Aspartame /g Sodium
Ascorbate / g Vol /ml
40 2.8 1.3 0 56.6 500
40 2.8 1.3 0 40 500
40 2.8 1.3 1.00 40 500
1.25 40 500
H4 40 2.8 1.3
40 2.8 1.3 1.50 40 500
In Figure 3, it is seen that the saltiness intensity is reduced by decreasing the amount of sodium
ascorbate in the solution (compare Hl vs H2). It is further seen that the saltiness is reduced most by
1.25g/500ml of aspartame.
Example 3: PEG-electrolyte solutions and taste testing
In an initial set of solutions containing PEG3350 (100g), sodium sulphate (9.0g), sodium chloride
(1.4g), potassium chloride (0.3g), it was found that the sweeteners sucralose (0.1%), aspartame (0.4%)
or a mixture of the two (sucralose 0.07% / aspartame 0.12%) were most effective in reducing the
perceived saltiness of the solution. Acesulfame-K, sodium saccharin and other mixtures were less
effective.
The solutions in Table 4 were prepared and taste tested. The results of the taste testing are shown in
Figure 4.
Table 4: PEG-electrolyte solutions
PEG3350 /g NaCl/g KCl /g Sucralose /g Citric Water to
Sol'n Na2S04 /g
Acid /g Vol /ml
1.4 0.3 0 0 500
II 100.0 9.0
1.4 0.3 0.50 0 500
100.0 9.0
13 100.0 9.0 1.4 0.3 0.50 0.375
1.4 0.3 0.50 0.50 500
14 100.0 9.0
100.0 9.0 1.4 0.3 0.50 0.625
The results of the taste testing are shown in Figure 4. It is seen that the solutions containing citric acid
were perceived as less salty than the solutions without citric acid.
Example 4: Bowel Cleansing Solutions
The following bowel cleansing solutions of the invention were prepared. For solution S1, the
components shown in Table 5 were combined in dry powder form and sealed in respective sachets A
and B as indicated in the table. The solution was then prepared by dissolving the contents in water to
the volume stated in the penultimate column. Solution S2 was prepared in an analogous manner.
Table 5
Sol'n Sachet A Sachet B
PEG3350 NaCl KCl/g Sucralose Fruit Citric Water V(350)
Na S04
/g /g Punch Acid /g to Vol /ml
/g (anhyd)/g
Flavouring /ml
100.00 9.00 2.00 1.00 0.476 0.469 0.792 750 1180
100.00 9.00 2.00 1.00 0.40 0.500 0.75 500 1210
For solution Tl, the components shown in Table 6 were combined in dry powder form and sealed in
respective sachets C and D as indicated in the table. The solution was then prepared by mixing the
contents of the two sachets together and then dissolving them in water to the volume stated in the
penultimate column. Solution T2 was prepared in an analogous manner.
Table 6
Sol'n Sachet C Sachet D
PEG3350 NaCl KCl Aspartame Orange Sodium Ascorbic Water V(350)
/g /g /g /g Flavour /g Ascorbate Acid / g to Vol /ml
/g /ml
Tl 40.00 3.20 1.20 1.93 0.60 48.11 7.54 500 1850
T2 40.00 2.50 0.90 1.10 0.80 40.00 0 500 1500
Example 4a - V(350) Osmolality measurements:
In order to assess the osmotic strength of the solutions, it was determined how much water was
required to provide a solution with measured osmolality of 350mOsmol/kg from the amounts of the
components in Tables 5 and 6.
To each solution prepared by dissolving the components in Tables 5 and 6 above in 500ml of
deionised water was added further deionised water until it reached an osmolality of 350mOsmol/kg.
The total volumes (including the initial 500ml) required to reach an osmolality of 350 mOsmol/kg are
recorded in Tables 5 and 6 in the final columns. Osmolalities were measured using an Advanced
Instruments, Inc Model 3250 osmometer. The osmometer was operated following standard
instructions: after the device passes a calibration check, the "Low Range" osmolality range (0 to 2000
mOsmol/kg) is selected, and a sample tube containing 250|j.l of sample solution is placed in the
freezing chamber. The "start" button is then pressed. When the measurement is completed, the
device displays the measurement result and that is recorded.
Example 4b - Bowel Cleansing
In a bowel cleansing study, subjects are given solutions SI or S2 in an evening followed by T1 or T2
the following morning. In a variant, subjects are given solution T1 or T2 in an evening followed by
SI or S2 the following morning.
Each subject receives the solution regimen in the split dose intake:
• Evening dose: Day 1; start intake between 17:00 and 18:00 for an intake period of up to 2 hours after
fasting from 14:00 hours.
• Morning dose: Day 2; start intake between 07:00 and 08:00 for an intake period of 2 hours.
Following each dose additional clear liquid will be consumed to make the total dose and additional
clear fluid ingested equal to at least 3L in the case of Arms 1 to 6, 8 and 9, and at least 2L in the case
of Arm 7.
Each dose of cleansing solution is reconstituted with water from the appropriate pair of sachets
containing powder for oral solution. The cleansing solution can be cooled in the fridge based on
subject preference. Evening cleansing solution dose is drunk within 2 hours after the start of the
intake on the evening of Day 1. At least the indicated additional clear fluid is also consumed,
preferably within 1 hour after the end of intake of cleansing solution in the evening.
In the morning of Day 2, the second dose is drunk within 2 hours after the start of intake. At least the
indicated additional clear fluid is also consumed, preferably within 1 hour after the end of intake of
cleansing solution in the morning. The total duration of each intake of cleansing solution and clear
fluid intake should normally not exceed 3 hours. Each subject is instructed to drink the assigned
cleansing solutions as 100 mL fractions every 10 minutes. The mandatory additional clear liquid
intake (water) after the cleansing solution intake can be taken by the subject as prefers, usually within
1 hour after completion of each cleansing solution intake. The start time and finish time of intake is
recorded. The volume of any cleansing solution or additional clear fluid left in the respective
containers is measured. In arms 6 to 9 the volume of fluid consumed ad libitum is monitored and
recorded.
Table 7:
Arm Arm 1 Arm 2 Arm 3 Arm 4 Arm 5
Evening SI (750ml) T1 (500ml) S2 (500ml) MOVIPREP T1 (500ml)
875ml 875ml 1000ml (1000ml) 1000ml
additional clear additional clear additional clear 500ml additional clear
fluid fluid fluid additional clear fluid
fluid
T1 (500ml) SI (750ml) T1 (500ml) MOVIPREP S2 (500ml)
Morning
875ml 875ml 1000ml (1000ml) 1000ml
additional clear additional clear additional clear 500ml additional clear
fluid fluid fluid additional clear fluid
fluid
Table 8:
Arm Arm 6 Arm 7 Arm 8 Arm 9
Evening S2 (500ml) S2 (500ml) S2 (500ml) MOVIPREP
Additional clear Additional clear Additional clear (1000ml)
fluid: minimum fluid: minimum fluid: minimum additional clear
1000ml or more ad 500 ml, or more ad 1000ml or more ad fluid: minimum
lib. lib lib 500ml or more ad lib
Morning T1 (500ml) T1 (500ml) T2 (500ml) MOVIPREP
Additional clear Additional clear Additional clear (1000ml)
fluid: minimum fluid: minimum fluid: minimum additional clear
1000ml or more ad 500 ml, or more ad 1000ml or more ad fluid: minimum
lib lib lib 500ml or more ad lib
Stool output is measured from the start of the intake on the evening of Day 1 and over the following
24 hours. "Stool" is the term used to refer to all bowel effluent. Mostly, it is liquid. The following
are also assessed
- Tolerability (vomiting rate).
- Time and volume of cleansing solution to reach a clear effluent.
In certain subjects, the following are also assessed:
- Colon cleansing success.
- The segmental cleansing scores for each of the five colon segments.
- Pharmacokinetic evaluation of key active ingredients: Ascorbate components and their metabolite
(oxalic acid) in blood, urine and faeces and PEG3350 and electrolytes in faeces at defined time points,
to demonstrate biological activities. Electrolytes in blood and urine are quantified using standard
clinical chemistry methods.
The study described above was carried out in two parts: Parts A and B.
Part A: In the part A, 120 subjects (70 male, 50 female) were allocated to the four study Arms, Arms
1 to 4. They were given the solutions as set out in Table 7. At the time of filing, the full statistical
analysis of the results is not complete. The interim results based on a preliminary analysis of the data
and available at the time of filing are shown in Table 9.
Table 9:
Arm Arm 1 Arm 2 Arm 3 Arm 4
Number of subjects 30 30/29* 30 30/29*
Mean Stool Weight (g) 2951g 3219g 3399g 2491g
Stool Weight 90% 2680g - 3222g 2963g - 3475g 3221g-3578g 2213g-2769g
confidence interval (g)
Protocol total IMP 1250ml 1250ml 1000ml 2000ml
volume
Protocol total additional 1750ml 1750ml 2000ml 1000ml
clear fluid volume
Vomiting rate 1 (3.33%) 3 (10%) 1 (3.33%) 1 (3.33%)
Overall, the compliance level was good. However, in each of Arms 2 and 4, 30 subjects began the
study, but one subject left the study after consuming the first solution, and before any stool sample
could be collected (thus 29 subjects are indicated (*)). The stool weight data are based on the set of
30 subjects for Arms 1 and 3, and on the set of 29 subjects for Arms 2 and 4. Both of those subjects
who left the study had the symptom of vomiting. They are included in the vomiting rate results.
It is seen that in each of Arms 1, 2 and 3 the subjects achieved a higher mean stool output weight than
in Arm 4, which represents a prior art colon cleansing solution. This was achieved with the subjects
in each of Arms 1, 2 and 3 consuming a lower total volume of bowel cleansing solution
(investigational medicinal product "IMP") than in Arm 4. The vomiting rate for Arm 2 was higher
than for the other arms. The vomiting rate for each of the solutions was within expected limits for a
bowel cleansing solution.
Part B: In part B, 120 subjects (54 male, 66 female) were allocated to the four study Arms, Arms 6 to
9. They were given the solutions as set out in Table 8. Mean stool output was highest in Arm 7 and
slightly lower in Arm 6. Arm 8 gave a lower mean stool output, but all of Arms 6, 7 and 8 gave a
higher mean stool output than Arm 9, which represents a prior art colon cleansing solution. Mean
stool output exceeded 2400g in all arms. Mean stool output in Arms 6 and 7 exceeded 3000g.
The subjects in part B underwent colonoscopy and the quality of cleansing was graded by the
colonoscopist, who was not aware of which cleansing treatment had been administered. Grading used
the Harefield Cleansing Scale. For details of the Harefield Cleansing Scale, see Halphen et al.
Gastrointestinal Endoscopy, 2013, 78, 121-131. The Harefield Cleansing Scale grades colon
cleansing as Grade A, B, C or D, A being the best. Grades A and B are considered a successful
cleansing; Grades C and D are considered an unsuccessful cleansing. At the time of filing, the full
statistical analysis of the results is not complete. The interim results based on a preliminary analysis
of the data and available at the time of filing are shown in Table 10.
Table 10:
Arm Arm 6 Arm 7 Arm 8 Arm 9
Number of subjects 30 30 30 30
Protocol total IMP volume 1000ml 1000ml 1000ml 2000ml
Protocol minimum total 2000ml 1000ml 2000ml 1000ml
additional clear fluid volume
Grade A 22 28 20 6
Grade B 8 2 7 21
Grade C 0 0 3 2
Grade D 0 0 0 1
It is seen in Table 10 that there was a higher proportion of Grade A cleansing in each of Arms 6, 7 and
8 than in Arm 9. This was achieved with the subjects in each of Arms 6, 7 and 8 consuming a lower
total volume of bowel cleansing solution (investigational medicinal product "IMP") than in Arm 9.
Example 5: Bowel Cleansing Solutions
The following bowel cleansing solutions of the invention are prepared. For solution S3, the
components shown in Table 11 are combined in dry powder form and sealed in respective sachets A
and B as indicated in the table. The solution is then prepared by dissolving the contents in water to
the volume stated in the far right-hand column. Solution S4 is prepared in an analogous manner
Table 11
Sol'n Sachet A Sachet
Water
PEG3350 Na S04 NaCl KCl Sucralose Mango Fruit Citric
/g (anhyd)/g /g /g /g Flavouring Punch Acid # to Vol
/g Flavouring /g /ml
S3 100.00 9.00 2.00 1.00 0.79 1.43 1.74 500
S4 100.00 9.00 2.00 1.00 0.79 1.59 1.74 500
# citric acid encapsulated with water soluble coating
For solution T3, the components shown in Table 12 are combined in dry powder form and sealed in
respective sachets C and D as indicated in the table. The solution is then prepared by mixing the
contents of the two sachets together and then dissolving them in water to the volume stated in the far
right-hand column. Solutions T4, T5 and T6 are prepared in an analogous manner.
Table 12
Sol'n Sachet C Sachet D
Orange
KCl Aspartame Citrus Sodium Ascorbic Water
PEG3350 NaCl
Gr'fruit
to Vol
/g /g /g /g Flavour Ascorbate Acid / g
flavour
/g /g /ml
40.00 3.20 1.20 0.875 1.6 48.11 7.54 500
40.00 3.20 1.20 0.875 2.1 48.11 7.54 500
Table 13
Sachet C Sachet D
Sol'n
Orange
PEG3350 NaCl KCl Aspartame Lemon Sodium Ascorbic Water
flavour
/g /g /g / Lime Ascorbate Acid / g to Vol
Flavour /g /ml
T5 40.00 2.50 0.90 1.625 40.00 500
40.00 2.50 0.90 1.625 2.15 40.00 500
Example 6: Regimens for Bowel Cleansing
Bowel cleansing is carried out using the following regimens;
Regimen A:
On the day before a colonoscopy examination:
- At approximately 18:00H patients take Formulation S2 in 500 mL of water over 30 minutes at a rate
of approximately 250 mL every 15 minutes until complete
- Patients drink 500 mL of additional water
- After an interval of 1-2 hours, the patients take Formulation T1 in 500 mL of water over 30 minutes
at the rate of 250 mL every 15 minutes until complete, followed by 500 mL of additional water
Colonoscopy is carried out the following day. The colonoscopy may be carried out in the morning (ie
before 12 noon). The colonoscopy may be carried out in the afternoon (ie after 12 noon).
Regimen B
On the day before colonoscopy:
- At approximately 18:00H, patients take Formulation S2 in 16 fl oz (500 mL) of water
- Patients drink 16 fl oz (500 mL) of mandatory additional water.
On the day of the colonoscopy:
- At approximately 06:00H, patients take Formulation T1 in 16 fl oz. (500mL) of water over 30
minutes at the rate of 250 mL every 15 minutes until complete.
- Patients drink 16 fl oz. (500 mL) of additional water.
Colonoscopy is carried out at least one hour after the last of the additional water is consumed. The
colonoscopy can be carried may in the afternoon (ie after 12 noon).
Regimen C
On the day of the colonoscopy:
- At approximately 05:00H, patients take S2 in 500 mL of water over 30 minutes at a rate of
approximately 250 mL every 15 minutes.
- Patients drink 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, patients take T1 in 500 mL of water over 30 minutes at a rate of 250 mL
every 15 minutes
- Patients drink 500 mL of additional water.
Colonoscopy is carried out at least one hour after the last of the additional water is consumed. The
colonoscopy can be carried may in the afternoon (ie after 12 noon).
Claims (21)
1. Use of a first colon cleansing solution comprising: (i) 70 to 250 g per litre polyethylene glycol having an average molecular weight of 2500 to 4500 Da., 5 (ii) 2.0 to 20 g per litre of one or more alkali metal sulphates, alkaline earth metal sulphates or a mixture thereof, (iii) optionally one or more electrolytes, (iv) optionally one or more flavouring agents, and (v) optionally one or more sweeteners; and a 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, 15 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; in the manufacture of a medicament for cleansing the colon of a subject before a diagnostic, therapeutic or surgical procedure; wherein the colon of the subject is to be cleansed by a method comprising: 20 - 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, whereby the first colon cleansing solution is taken over a time period t(d1) followed by optional additional water based beverage 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) 25 followed by optional additional water based beverage over a time period t(cf2), whereby the subject undergoes the surgical, therapeutic or diagnostic procedure at a time t after the beginning of the colon cleansing method, and whereby the time interval after the completion of the second additional water based beverage and the start of the surgical, therapeutic or diagnostic procedure is t(procedure interval); 30 and wherein: (i) t is in the range of from 10 to 36 hours; t(dose interval) is in the range of from 0 to 8 hours; and t(procedure interval) is in the range from 8 to 20 hours; or (ii) t is in the range of from 10 to 36 hours; 5 t(dose interval) is in the range of from 8 to 20 hours; and t(procedure interval) is in the range from 30 minutes to 10 hours; or (iii) t is in the range of from 3 to 14 hours; t(dose interval) is in the range of from 0 minutes to 8 hours; and t(procedure interval) is in the range from 30 minutes to 10 hours. 10
2. The use as claimed in claim 1, wherein in the method of cleansing the colon of the subject, 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), 15 - 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 is in the range of from 3 to 14 hours (for example from 4 to 10 hours); and 20 - t(procedure interval) is from 30 minutes to 10 hours (for example from 1 to 6 hours).
3. The use as claimed in claim 2 wherein: - t(d1) is 30 minutes; - t(cf1) is 30 minutes; - t(dose interval) is one hour or two hours; 25 - t(d2) is 30 minutes; - t(cf2) is 30 minutes. - t2 is in the range of from 4 to 8 hours; and - t(procedure interval) is from 1 to 6 hours.
4. The use as claimed in claim 1, wherein in the method of cleansing the colon of the subject, the 30 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 is in the range of from 10 to 36 hours (for example from 12 to 24 hours, for example from 12 to 16 5 hours); and - t(procedure interval) is from 8 to 20 hours (for example from 10 to 16 hours).
5. The use as claimed in claim 4 wherein: - t(d1) is 30 minutes; - t(cf1) is 30 minutes; 10 - t(dose interval) is one hour or two hours; - t(d2) is 30 minutes; - t(cf2) is 30 minutes. - t is in the range of from 10 to 36 hours; and - t(procedure interval) is from 8 to 20 hours. 15
6. The use as claimed in claim 1, wherein in the method of cleansing the colon of the subject, 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 on the morning of the diagnostic, therapeutic or surgical procedure - t(d1) is 15 minutes to 1 hour (for example 30 minutes); 20 - 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 is in the range of from 10 to 36 hours (for example from 12 to 24 hours, for example from 12 to 16 25 hours); and - t(procedure interval) is from 30 minutes to 10 hours (for example from 1 to 6 hours).
7. The use as claimed in claim 6 wherein: - t(d1) is 30 minutes; - t(cf1) is 30 minutes; 30 - t(dose interval) is in the range of from 8 to 20 hours; - t(d2) is 30 minutes; - t(cf2) is 30 minutes. - t is in the range of from 10 to 36 hours; and - t(procedure interval) is from 1 to 6 hours.
8. The use as claimed in any one of claims 1 to 7, wherein the method of cleansing the colon of the subject comprises the subject taking from 250ml up to 1000ml of the second cleansing solution.
9. The use as claimed in any one of claims 1 to 8, wherein the method of cleansing the colon of the subject comprise the subject taking from 400ml up to 1100ml of the first cleansing solution. 5
10. The use as claimed in any one of claims 1 to 7, wherein the first cleansing solution has a volume of 500ml or 750ml, and the second cleansing solution has a volume of 500ml.
11. The use as claimed in any one of claims 1 to 10, wherein the method of cleansing the colon of the subject comprises the subject taking additional water based beverage after one or both of the first and second colon cleansing solutions. 10
12. The use as claimed in claim 11, in which the method of cleansing the colon of the subject comprises the subject taking 300 ml to 1000 ml of additional water based beverage after each of the first and second colon cleansing solutions.
13. The use as claimed in any one of claims 1 to 12, wherein the second colon cleansing solution comprises: 15 a) (i) 12 to 20g per litre ascorbic acid and (ii) 80 to 120g per litre sodium ascorbate the components (i) and (ii) being present in a weight ratio of from 1:5.063 to 1:7.875; b) 60 to 100g per litre polyethylene glycol having an average molecular weight of 3000 to 4000 Da; 20 c) 3 to 8g per litre sodium chloride and 1 to 7g per litre potassium chloride; d) one or more flavouring agents; and e) one or more sweeteners.
14. The use as claimed in any one of claims 1 to 13, wherein the first colon cleansing solution comprises: 25 (i) 175 to 220 g per litre polyethylene glycol having an average molecular weight of 2500 to 4500 Da. (ii) 15 to 20 g per litre of one or more alkali metal sulphates, alkaline earth metal sulphates or a mixture thereof (iii) 3.0 to 5.0 g per litre sodium chloride, and 1.5 to 2.5 g per litre potassium chloride; 30 (iv) optionally one or more flavouring agents; and (v) optionally one or more sweeteners.
15. The use as claimed in any one of claim 1 to 14, wherein the first colon cleansing solution comprises: (i) 100 g polyethylene glycol having an average molecular weight of 3000 to 4000 Da; (ii) 9.0 g sodium sulphate; 5 (iii) 2.0g sodium chloride and 1.0g potassium chloride; (iv) optionally one or more flavouring agents; and (v) optionally one or more sweeteners.
16. The use as claimed in any one of claims 1 to 15, wherein the second colon cleansing solution comprises: 10 a) (i) 7.54 g ascorbic acid and (ii) 48.11 g sodium ascorbate b) 40g polyethylene glycol having an average molecular weight of 3000 to 4000 Da; c) 3.20g sodium chloride and 1.20g potassium chloride; 15 d) one or more flavouring agents; and e) one or more sweeteners.
17. The use as claimed in claim 2 or claim 3 wherein the method of cleansing the colon of the subject 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 20 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 25 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 100.00g polyethylene glycol 3350, 9.00g Na SO (anhyd), 2.00g NaCl, 1.00g KCl, 0.40g sucralose, 0.500g Fruit Punch Flavouring and 0.75g Citric Acid in 30 water to a volume of 500ml, and solution T1 being a solution comprising 40.00g polyethylene glycol 3350, 3.20g NaCl, 1.20g KCl, 1.93g Aspartame 0.60g Orange Flavouring, 48.11g Sodium Ascorbate and 7.54g Ascorbic Acid in water to a volume of 500ml.
18. The use as claimed in any one of claims 9 to 14, wherein the method of cleansing the colon of the subject is carried out on the day before a colonoscopy of a subject, and 35 - 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; 5 - The subject drinks 500 mL of additional water; and - Colonoscopy is carried out the following day, solution S2 being a solution comprising 100.00g polyethylene glycol 3350, 9.00g Na SO (anhyd), 2.00g NaCl, 1.00g KCl, 0.40g sucralose, 0.500g Fruit Punch Flavouring and 0.75g Citric Acid in water to a volume of 500ml, and solution T1 being a solution comprising 40.00g polyethylene glycol 10 3350, 3.20g NaCl, 1.20g KCl, 1.93g Aspartame, 0.60g Orange Flavouring, 48.11g Sodium Ascorbate and 7.54g Ascorbic Acid in water to a volume of 500ml.
19. The use as claimed in any one of claims 6 to 7, wherein the method of cleansing the colon of the subject comprises: on the day before the colonoscopy: - At approximately 18:00H, the subject takes Formulation S2 in 16 fl oz (500 mL) of water; 15 - 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. (500mL) 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 20 - Colonoscopy is carried out at least one hour after the last of the additional water is consumed; solution S2 being a solution comprising 100.00g polyethylene glycol 3350, 9.00g Na SO (anhyd), 2.00g NaCl, 1.00g KCl, 0.40g sucralose, 0.500g Fruit Punch Flavouring and 0.75g Citric Acid in water to a volume of 500ml, and solution T1 being a solution comprising 40.00g polyethylene glycol 3350, 3.20g NaCl, 1.20g KCl, 1.93g Aspartame, 0.60g Orange Flavouring, 48.11g Sodium Ascorbate 25 and 7.54g Ascorbic Acid in water to a volume of 500ml.
20. The use as claimed in any one of claims 1 to 19, wherein in the method of cleansing the colon of the subject, the subject is not to eat heavy meals before starting the colon cleansing treatment, or the subject is to fast for 12 hours before starting the colon cleansing treatment, or the subject is to follow a “white diet” for a day before, or the day of the start of the colon cleansing procedure, or the subject 30 is 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, 35 parsnip, semolina, banana and popcorn.
21. The use according to claim 1, substantially as hereinbefore described with particular reference to any one of the examples and/or figures thereof.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US14/202,098 US20140186470A1 (en) | 2012-09-11 | 2014-03-10 | Compositions |
PCT/EP2015/054856 WO2015135880A1 (en) | 2014-03-10 | 2015-03-09 | Method of cleansing the colon |
Publications (2)
Publication Number | Publication Date |
---|---|
NZ723017A NZ723017A (en) | 2023-10-27 |
NZ723017B2 true NZ723017B2 (en) | 2024-01-30 |
Family
ID=
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2018204694B2 (en) | Compositions comprising peg and ascorbate | |
JP7011629B2 (en) | How to clean the colon | |
AU2015228962B2 (en) | Method of cleansing the colon | |
NZ723017B2 (en) | Method of cleansing the colon | |
CN115154464A (en) | Method for cleansing colon | |
IES20130273A2 (en) | Compositions comprising PEG and ascorbate |