EDIBLE SEMI-SOLID COMPOSITION FOR USE IN PATIENTS UNDERGOING ENDOSCOPY INCLUDING COLONOSCOPY

Abstract

The present invention relates to a GI-cleansing composition comprising i) one or more gelling or swelling agents, ii) one or more laxative agents, iii) one of more taste-improving agents, and iv) water.

Claims

1-26. (canceled)

27. A GI-cleansing composition comprising: (i) one or more gelling or swelling agents, (ii) one or more laxative agents, (iii) one or more taste-improving agents, and (iv) water.

28. A GI-cleansing composition, wherein from about 100 to about 500 mL of the composition provides one dose of the one or more laxative agents.

29. A GI-cleansing composition according to claim 27, wherein the concentration of the gelling or swelling agent is from about 0.1 to about 15% w/w of the total weight of the composition.

30. A GI-cleansing composition according to claim 27, wherein the concentration of the gelling or swelling agent is from about 2 to about 7% w/w of the total weight of the composition.

31. A GI-cleansing composition according to claim 27, wherein the concentration of the gelling or swelling agent is from about 0.1 to about 5% w/w of the total weight of the composition.

32. A GI-cleansing composition according to claim 27, wherein the concentration of the laxative agent is from about 25 to about 80% w/w of the total weight of the composition.

33. A GI-cleansing composition according to claim 27, wherein the concentration of the laxative agent is from about 35 to about 70% w/w of the total weight of the composition.

34. A GI-cleansing composition according to claim 27, wherein the taste-improving agent is selected from fruit extracts, vanillin, citrus, lemon, cinnamon, ginger, and mixtures thereof.

35. A GI-cleansing composition according to claim 27, wherein the concentration of the taste-improving agent is from about 0.02 to about 20% w/w of the total weight of the composition.

36. A GI-cleansing composition according to claim 27, wherein the taste-masking agent is a fruit extract and the concentration thereof in the composition is from about 1 to about 20% w/w of the composition.

37. A GI-cleansing composition according to claim 27, comprising vanillin, citrus, lemon, cinnamon, or ginger as the taste-masking agent, wherein the concentration thereof in the composition is from about 0.02 to about 2% w/w of the composition

38. A GI-cleansing composition according to claim 27, wherein the concentration of water is from about 15 to about 60% w/w of the total weight of the composition.

39. A GI-cleansing composition according to claim 27, wherein the concentration of water is from about 20 to about 60% w/w of the total weight of the composition.

40. A GI-cleansing composition according to claim 27, wherein the concentration of water is from about 25 to about 60% w/w of the total weight of the composition.

41. A GI-cleansing composition according to claim 27, wherein the gelling or swelling agent is selected from agar, guar gum, carrageenan, locust bean gum, acacia gum, xanthan gum, karaya gum, tara gum, and mixtures thereof.

42. A GI-cleansing composition according to claim 27, wherein the gelling or swelling agent is selected from gellan, pectin, konjak, and mixtures thereof.

43. A GI-cleansing composition according to claim 27, wherein the gelling or swelling agent is selected from gellan, agar, pectin, and mixtures thereof.

44. A GI-cleansing composition according to claim 27, wherein the gelling or swelling agent is selected from carrageenan, locust bean gum, and mixtures thereof.

45. A GI-cleansing composition according to claim 27, wherein the taste-improving agent is a laxative.

46. A GI-cleansing composition according to claim 27, wherein the taste-improving agent is selected from prune extract, plum extract, fig extract, coffee extract, and mixtures thereof.

47. A GI-cleansing composition according to claim 27, wherein the laxative is selected from PEGs having a molecular weight of from about 2000 to about 8000.

48. A GI-cleansing composition according to claim 27, wherein the laxative is PEG 3350.

49. A method of treating or alleviating constipation, comprising administering a composition according to claim 27 to a subject in need thereof.

50. A method of endoscopy, comprising administering a composition according to claim 27 to a subject in need thereof.

51. A method of treating an overweight subject, comprising administering a composition according to claim 27 to a subject in need thereof.

52. A method of treating obesity, comprising administering a composition according to claim 27 to a subject in need thereof.

Description

LEGENDS TO FIGURES

[0194] FIG. 1 show the structure of the three samples from example

[0195] FIGS. 2-4 show images of the samples with 100 magnification;

[0196] FIGS. 2-3: Note the globular particles (dispersed phase) and their size

[0197] FIG. 4 is the batch used in the clinical testing

[0198] FIGS. 5A-C show the microscopic structure as the two phases are mixed illustrating the spontaneous formation of the globular particles at the interphase between the 2 phases. The 3 pictures (FIG. 5A-C) were taken at 30 seconds intervals

[0199] FIG. 6-7 show the results of the rheological measurements

[0200] FIG. 8 shows the result of the clinical study on a BBP scale

[0201] The invention is further illustrated in the following, non-limiting examples

EXAMPLES

Example 1

A Composition According to the Invention to be Administered Twice

[0202] The composition below is intended to be administered the evening before and/or the morning before colonoscopy. Thus, it contains 50% of the active ingredients. Compositions may also be made eg where one of the compositions contains 40% of the total dose and the other contains 60% of the total dose. Other percentage distributions may also be employed and a person skilled in the art will know how to adjust the ingredients in order to arrive at such compositions. One of two doses (One portion evening OR morning)

[0203] A. General Composition to which Additives and Adjusting Agents May be Added:

TABLE-US-00001 Ingredient Amount (g) 1. Laxative (eg Macrogol 3350) 100 2. Water 100 3. Taste-improving agent (laxative properties) 25 g 4. Gelling or swelling agent 7.5-15 g

[0204] step a. mix 1, 2, 3, and 4, and blend.

[0205] step b. bring to boil.

[0206] step c. Pour into container and allow the mix to set.

[0207] Amount before step b=232.5-240 g Amount after step c=about 220 g (about 10% reduction in weight)

[0208] B. Specific Composition Containing Gellan as a Gelling or Swelling Agent:

TABLE-US-00002 Ingredient (Gellan) Amount (g) 1. Macrogol 3350 100 2. Lactulose 40 3. Potassium chloride 1 4. Sodium chloride 2 5. Sodium citrate 7.5 6. Water 100 7. Prune extract 25 8. Anisyl alcohol 0.5 9. Gellan 7.5-15

[0209] step a. mix 1, 2, 3, 4, 5, 6, 7, 8 ad 9 and blend.

[0210] step b. bring to boil.

[0211] step c. Pour into container and allow the mix to set.

[0212] Amount before step b=0.275 kilograms

[0213] Amount after step c=0.251 kilograms

[0214] C. Specific Composition Containing Agar as a Gelling or Swelling Agent

TABLE-US-00003 Ingredient (Agar) Amount (g) Macrogol 3350 100 Lactulose 40 Potassium chloride 1 Sodium chloride 2 Sodium citrate 7.5 6. Water 100 Prune extract 25 Anisyl alcohol 0.5 agar powder 7.5-15

[0215] step a. mix 1, 2, 3, 4, 5, 6, 7, 8 ad 9 and blend.

[0216] step b. bring to boil.

[0217] step c. Pour into container and allow the mix to set.

[0218] Amount before step b=0.275 kilograms

[0219] Amount after step c=0.254 kilograms

[0220] D. Specific Composition Containing Pectin as a Gelling or Swelling Agent

TABLE-US-00004 Ingredient (Pectin) Amount (g) Macrogol 3350 100 Lactulose 40 Potassium chloride 1 Sodium chloride 2 Prune extract 25 6. Water 100 Anisyl alcohol 0.5 Pectin 7.5

[0221] step a. mix 1, 2, 3, 4, 5, 6, 7, 8 ad 9 and blend.

[0222] step b. bring to boil.

[0223] step c. Pour into container and allow the mix to set.

[0224] Amount before step b=0.275 kilograms

[0225] Amount after step c=0.248 kilograms

Example 2

A Composition According to the Invention Including Crme Sauce

[0226] The compositions as described in Example 1 are made, but only using 80% of the gelling and swelling agent. This result in that the gelling or swelling agent exhibits syneresis, i.e. some of the liquid is not totally sorbed by the gelling or swelling agent and a crme sauce like-structure appears.

[0227] Alternatively, a crme sauce may be prepared by preparing the compositions of Example 1, but leaving out the gelling or swelling agent. The dose of the crme sauce (in a twice split dose regimen) may be from 10 to 50% w/w of the weight of the sauce obtained.

Example 3

A Novel Bowel Cleansing Pudding Formulation

Formulation

[0228] Content for one 250 g portion of pudding

TABLE-US-00005 Components Weight (g) Polyethylene glycol 3350 (PEG, Macrogol, 100 Pharma quality from DOW) Lactulose Powder 40 Potassium chloride 1.12 Sodium citrate-dihydrate 5.17 Calcium carbonate 1 MiliQ-Water 100 ml Prune concentrate (Rynkeby) 25 Vanillin 0.2 K-dominated-Carrageenan (GENU LACTA) 0.5 Carob (GENU GUM) 0.5

[0229] Apparatus used in preparation of the pudding

TABLE-US-00006 Apparatus Magnetic stirrers 250 mL Erlenmeyer flask Water bath (50 C.) Metal bowl x2 Food mixer with whisk attachment Disposable weighing boats Magnetic stirrer hot plate x2 Large spoons Weighing scales Glass bowl/beaker as final vessel for pudding Thermometers Small spoons and spatulas

Procedure:

[0230] To produce a 250 g portion of pudding. Phase 1 and phase 2 must be produced separately before mixing.

Phase 1:

[0231] 1. Warm the metal bowl of the food mixer in a water bath set to 50 C. for 10-20 minutes. [0232] 2. Weigh out and combine 100 g PEG, 1.12 g potassium chloride, 5.17 g sodium citrate, 1 g calcium carbonate, and 1 g vanillin and set aside. [0233] 3. Heat the 25 g prune concentrate with 20 ml of warm water using the magnetic stirrer hot plate to around 40 C. Once it has come to temperature, add the prune and water mixture to the pre heated food mixer. [0234] 4. Then slowly add the powders to the food mixer (containing the prune and water), and mix on a high speed until fully combined. [0235] 5. Transfer the metal bowl of the food mixer back to the water bath, to heat to 40 C. Keep stirring this regularly using the whisk attachment from the food mixer, until a smooth, homogenous phase is formed.

Phase 2:

[0236] 1. Heat 60 ml 66.7% Lactulose Solution and 60 ml water to 95 C. using a magnetic stirrer hot plate and electronic contact thermometer. Use a tall, thin beaker for this in order to achieve an effective vortex. Cover beaker with aluminium foil to speed up the process. [0237] 2. Meanwhile combine 0.5 g carrageenan, 0.5 g carob (Locust Bean Gum. [0238] 3. Once the water has come to temperature, add the polymers at a steady speed, aiming for the powder to hit the side of the vortex (to ensure rapid dispersion). [0239] 4. Wait until the solution becomes clear with no particulates, while keeping at 90 C. under agitation.

[0240] Combining Phase 1 and 2 [0241] 1. Once phase 1 is completely dissolved (within the water bath) place the metal bowl back on the food mixer and start to mix on a fast speed. [0242] 2. Let phase 2 cool to around 60 C., then add slowly into the food mixer, ensuring that the stream of liquid hits as close to the side of the metal bowl as possible. [0243] 3. Continue to mix on a high speed until the two phases are fully combined, and the colour and consistency start to change. [0244] 4. Wait until the formulation reaches 25 C., still continually mixing, before pouring into glass beakers.

Example 4

Basic Formulation and Procedure

[0245] Content for one 250 g portion of pudding

TABLE-US-00007 Component Weight (g) Polyethylene glycol 3350 (PEG, Macrogol, 100 Pharma quality from DOW) Lactulose (NN) 40 Potassium chloride 1.12 Sodium citrate-dihydrate 5.17 Calcium carbonate 1 MiliQ-Water 100 Prune concentrate (Rynkeby) 25 Vanillin extender flavour (Firmenich) 0.5 -Carrageenan (kappa carrageenan) 1.5

Procedure:

[0246] To produce a 250 g portion of pudding. Phase 1 and phase 2 must be produced separately before mixing.

Phase 1:

[0247] 1. Weigh 100 g PEG and place it in an Erlenmeyer flask. Add 50 mL water to the flask. Heat using a heat plate to 33 C. while stirring with a magnetic bar until complete dissolution (the solution will be visibly clear).

Phase 2:

[0248] 1. (a) Weigh off, and mix together in a bowl; 40 g lactulose, 1.12 g potassium chloride, 5.17 g sodium citrate, 1 g calcium carbonate, 25 g prune concentrate and 0.5 g vanillin extender flavour. [0249] 2. (b) Weigh off 1.5 g -Carrageenan and sprinkle it, under vigorous stirring, onto 50 mL water in the plastic cup (1 L) of an immersion blender. Pour the solution in a bowl and heat it to 90 C. Once the temperature reaches 90 C., let the solution cool to 60 C. at room temperature. [0250] 3. When the temperature of (b) reaches 60 C., pour it into (a) and mix together with a large the immersion blender (this seems to give a more stable overall result compared to mixing with a spoon of whisk). Place the solution in the water bath for a couple of minutes to achieve a more homogeneous blend.

Mixing of Phase 1 and Phase 2:

[0251] 1. Mix phase 1 and Phase 2 at room temperature by pouring phase 1 in phase 2 and mixing with a large spoon or a whisk (not an immersion blender as this results in a weaker emulsion). [0252] 2. Pour the formulation into the glass bowl, let the air bubbles resolve and cover it with Parafilm. Place the serving bowl with the formulation in a 18 C. freezer overnight and then refrigerate it (at 5 C.). Note: After freezing overnight (at least 8 hours), it is very important to immediately transfer the formulation from the freezer to a refrigerator, as it has an influence on the stability of the formulation.

Example 5

Taste-Masking

Vanilla Flavour

[0253] The taste/flavour of the pudding was first to be adjusted by varying the concentrations and forms of vanilla flavouring as seen below in Table 1, The percentages were chosen as this almost represents a logarithmic scale. The pudding was produced per procedure in Example 4 with only the vanilla element changing. The results were assessed by a taste panel.

TABLE-US-00008 TABLE 1 Vanilla Extender Flavour (VEG) Vanillin Ethyl-Vanillin 0.15 g 0.15 g 0.15 g 0.5 g 0.5 g 0.5 g 1.5 g 1.5 g 1.5 g

[0254] Vanillin was found to be superior. The concentration was further adjusted throughout the investigation, and assessed again using a taste panel, as seen in Table 2 and 3:

TABLE-US-00009 TABLE 2 0.05 g 0.1 g 0.2 g 0.3 g 0.4 g 0.5 g Initial adjustments 0.1% 0.2% 0.4% 0.6% 0.8% 1% (Concentration in 50 g of pudding)

TABLE-US-00010 TABLE 3 0.2 g 0.6 g 1 g 1.5 g Further adjustments in the reduction 0.08% 0.24% 0.4% 1% in vanillin (concentration in 250 g of pudding)

[0255] The vanillin (Sigma Aldrich) was the preferred flavour according to the taste panel. See Table 4 below regarding the rankings of the pudding:

TABLE-US-00011 TABLE 4 Ranking Flavour used per 50 g pudding 1.sup.st place 0.3 g Vanillin - creamy Joint 2.sup.nd place 0.03 g Vanilla Extender Flavour (VEF), 0.3 g VEF 3.sup.rd place 0.1 g Vanillin 4.sup.th place 0.3 g Ethyl Vanillin 5.sup.th place 0.1 g Ethyl Vanillin 6.sup.th place 0.1 g VEF 7.sup.th place 0.03 g Vanillin 8.sup.th place 0.03 g Ethyl Vanillin Joint 1.sup.st place 0.2 g vanilli., 0.3 g vanillin Joint 2.sup.nd place 0.05 g Vanillin, 0.5 g Vanillin 3.sup.rd place 0.4 g Vanillin 4.sup.th place 0.1 g Vanillin

[0256] Due to the results of the taste panel, at first 0.3 g Vanillin in 50 g (0.6% w/w) was selected for use in the clinical testing. However, while making the protocol for the clinical trial batch at HB Medical, the puddings were tasted again and it was found that the flavour of vanilla gets too strong after a couple of mouthfuls of pudding. Hence, further adjustments were made. 0.2 g Vanillin (0.08%) was used as a starting point for the final vanillin concentration in the clinical test studies. Due to the content of vanillin, it may be considered to add an antioxidant to avoid any oxidation of vanillin to vanillic acid.

Example 6

Carrageenan Concentration

[0257] In an attempt to remove the freezing process from the procedure, the k-dominated-carrageenan concentrations were increased (see Table 5 and 6), but it was found to be impossible to disperse and dissolve in cold water. A hand-blend was used to initially disperse the carrageenan in cold water, then dissolve it in hot (90 C. water), as per Example 4. Using the vortex method (as explained in the Handbook of Pharmaceutical Excipients (Rowe, 2006)) and with the water at 90 C., the carrageenan dispersed and dissolved simultaneously, and agitation was continued until full hydration is achieved. Also dry-blending the carrageenan with the lactulose acted to adequately disperse the polymer.

TABLE-US-00012 TABLE 5 Carrageenan concentration 0.6 g 1.2 g 2.4 g Initial variations to 0.6% 1.2% 2.4% carrageenan (in 100 g pudding)

TABLE-US-00013 TABLE 6 Carrageenan concentration 0.3 g 0.4 g 0.6 g 0.8 g 1 g Further adjustments, 0.6% 0.8% 1.2% 1.6% 2% using 50 g pudding sample

[0258] Changed to vortex method with a 3 g in 250 g concentration (1.2%).

[0259] Both - and iota carrageenan were used.

[0260] The results showed that better results were obtained if the carrageenan-carob phase to was heated to almost the boiling point, heating the PEG phase to +/50 C. under frequent stirring for a time long enough to form an homogenous mixture and mixing the phases at the same temperature, 33 C., for both. Then freezing overnight and transferring to a refrigerator (+5)

Procedure Adjustments

[0261] The main focus was to vary the production temperatures (the examples found in Table 7) to improve the gelling of the pudding and to avoid a step of cooling. The type of carrageenan used was also changed from using the k-dominated carrageenan to iota-carrageenan, using the same concentrations (1.5 g in a 250 g batch of pudding). All adjusted formulations were stored at freezer, fridge and room temperature, to see if the pudding set without the need for the freezer, and to assess the texture.

TABLE-US-00014 TABLE 7 Temperature adjustments Phase 1 Phase 2 Mixing Adjustment 1 Increase temperature Keep temperature at Mix under efficient stirring to approximately 60 C. (at 60 C.) and fill immediately 60 C. into glass bowls Adjustment 2 Keep temperature Mix phase 2 (b) at Immediately after phase at 33 C. (as 90 C. with the phase 2 2 (a) and (b) are combined. original method) (a). Mix this hot solution with phase 1. Adjustment Keep at 33 C. Keep phase 2 (a) at Mix phase 2 (b) with the 3 (cold process) room temperature, other phase under efficient and mix with phase 1. mixing. Make phase 2 (b) as usual but cool to room temperature.

[0262] From the table above, Phase 1: PEG and water. Phase 2 (a): lactulose, potassium chloride, sodium citrate, calcium carbonate, prune concentrate and vanillin extender flavour. Phase 2 (b): -dominated carrageenan and water.

[0263] Tests were also made where the mixing technique was also reversed so instead the polymer phase (carrageenan+carob phase) was added to the PEG phase in the aim to get a different gel consistency. The samples were then left to set directly in the refrigerator or in the freezer overnight and then transferred to the refrigerator. The samples which were in the freezer overnight appeared more homogeneous and, compared to those which were all the time in the refrigerator displayed a lesser tendency to separate.

Example 7

Addition of Carob

[0264] Carob (LBG) was added to the formulation to strengthen the gel, the aim was to stabilise the w/w emulsion using this method. Equal quantities of carrageenan to carob were tested, originally 1.5 g, but reduced eventually to 0.5 g. The carob was added to the carrageenan and lactulose phase, so all the polymers were together, and so the lactulose could aid dispersion. Below details the carob adjustment made over time. The batches were stored in the freezer, refrigerator and at room temperature and then compared.

TABLE-US-00015 Carrageenan concentration (g) Carob concentration (g) In 250 g pudding In 250 g pudding 1.5 g 1.5 g 1.2 g 0.8 g 0.5 g 0.5 g 0.5 g 0.5 g 0.5 g 0.3 g

[0265] The addition of carob improved the mouthfeel of the pudding, and seemed to give a smoother texture. The original 1.5 g carrageenan and 1.5 g carob set to a firm gel in the refrigerator but the high concentration of gelling agents meant that even with the vortex method, the polymers were difficult to disperse and dissolve. It was found that even with the lower concentrations, the formulation still set in the refrigerator; aided by the reversal of the mixing technique. Where the carob allowed the pudding to set in the refrigerator, the carrageenan concentration was able to be reduced; this made the dispersion of the polymers much more simple, which was a benefit when it came to upscaling.

[0266] The formulations with the carob nearly set at room temperature with the repeat of batch from FIG. 1, being very close to perfectly setting.

Example 8

Microscopic Assessment

[0267] A light microscopea Leica DM750 with the Leica ICC50 HD Digital Camera Module, was used to visualize the w/w emulsion. A tiny sample of the finished pudding was loaded onto a microscope slide and images were taken on both the 40 band the 100 magnification settings using the LAS V4.1 computer system. Comparisons were made between the images containing carob, and those without carob as well as different samples with varying storage temperatures. The final sample made at HB medical was also imaged to assess the variation when scaling up production.

[0268] To further investigate the water-in-water emulsion, the two separate phases where mixed together under the microscope to observe the formation of the emulsion as a microscopic level. The two phases were produced per procedure (Example 3), and left to set in the freezer overnight. The PEG phase was added first to the microscope slide and a cover slip was placed on top. Then a drop of the carrageenan phase was placed next to the cover slip and left to mix with the PEG via capillary action. A Nikon Eclipse Ti microscope was used for this as it gave a better depth of field. Images were taken at various points to show the development of the emulsion droplets.

[0269] A phase diagram of PEG was obtained using the DSC. 15 microliters of PEG suspension was used. Started at 5 C., increasing up to 80 C., with an increase of 5 C. every minute.

Microscopic StructuresFIGS. 2, 3, 4, 5A-C

[0270] FIGS. 2, 3 and 4 support the initial concept of formation of a water-in-water emulsion, with droplets of an aqueous dispersed phase within an aqueous continuous phase and it is suggested by the images that these phases are immiscible when mixed together. There is no oil or hydrophobic components within the formulation so a typical oil-in-water emulsion cannot be formed. Much less is known about a water-in-water emulsion compared to the typical oil-in-water so it is difficult to verify. However, based on the photos there is a clear indication that two phases are formed The kinetic stability of the emulsion may be difficult to control as surfactants do not adsorb onto the w/w interface (hence surfactants cannot be used as an interphase between the two hydrophilic phases). One way of stabilisation is by gelling one or both of the phases to keeping the two phases dispersed (Nguyen et al., 2013). In the pudding formulation the carrageenan phase is acting as the gelling phase, which could explain why the formulation stays in the water-in-water emulsion (if the gel is set quickly enough) and doesn't separate out into two distinct phase.

[0271] FIGS. 5A-C show the microscopic structure as the two phases are mixed illustrating the spontaneous formation of the globular particles at the interphase between the 2 phases. The 3 pictures (FIG. 5A-C) were taken at 30 seconds intervals

Example 6

Rheological Studies

[0272] Finally, the rheology of the pudding was studies to compare the stiffness/hardness of the gel of the pudding containing carob vs the one without, and to test the sample for the clinical trial. The rheological measurements were performed on a controlled stress rheometer (AR-G2 Rheometer). Small deformations measurements were obtained using a plate with diameter of 40 cm with an evaporation protection cap. The gap was adjusted to 400 m (in order to allow for an adequate sample of my pudding to be tested) and the mode was changed to stiff bearing mode. The rheological measurements were performed at 5 C. Frequency and stress sweeps were set up using an oscillation stress of 0.8 Pa (as a stress sweep was used to determine the linear viscoelastic region, and at 0.8 Pa the gel did not break (Malvern.Instruments.Ltd, 2005)). The number of tests run per sample were 3-4. The data was recorded in the Data Analysis programme for the AR-G2 Rheometer and analysed and stored in Microsoft Excel.

Rheology Results

[0273] Small deformation rheology was carried out on the 3 carrageenan gels to measure and compare the elastic modulus G.

[0274] Sample 1 was a standard pudding formulation, as in Example 2 containing 0.2% carob (and 0.2% -dominated carrageenan); sample 3 was a pudding produced from the older method, that did not contain carob but contained 0.6% carrageenan as in example 4; sample 2 was from the final clinical trial batch, produced with 0.2% carob and 0.2% carrageenan but using the adjusted method, as in example 2, for upscaling.

[0275] The results of the frequency sweep and stress sweep are shown in FIGS. 6 and 7. The frequency sweep is used to assess the stiffness/hardness of the gel over time and the stress sweep measures at what stress (Pa) the gel breaks at. From the frequency sweep, sample 2 pudding is shown to be softer and less brittle than the others. It likely to deform at a lower stress value. Samples 1 and 3 are confirmed to be a harder gel, and more brittle. They will likely deform at a higher stress value compared to sample 2. A one-way ANOVA was completed, including a Tukey's multiple comparisons test to assess the significance of the differences, as shown in FIG. 7. The p-values verify that there is no significant difference between the hardness of gel with and without carob (between sample 1 and 3), however sample 2 is significantly different.

[0276] Sample 2 is measured as being a softer gel, as the gelling network within the sample differs from the other samples.

[0277] Interestingly, sample 1 and 3 were not statistically different regarding both the hardness of the gel and the force at which the gel breaks despite one containing carob and one containing a significantly higher concentration of carrageenan. There appears to be no difference between 0.2% carrageenan PLUS 0.2% carob versus 0.6% carrageenan. This suggests that the carob acts to strengthen the gel more than just carrageenan alone.

Example 9

Patient Use of the Pudding

[0278] The 273.49 g portion of the pudding (that equates to the standard 100 g dose of PEG) should be consumed gradually over a 1-hour period, while drinking at least 1 L of cold water over this time. For example, one quarter of the pudding (roughly 68 g) every 15 minutes with 1 glass of water.

[0279] Timetable for initial clinical trial with bowel cleansing pudding:

TABLE-US-00016 Time Activity 12.00 - day before Low Residue Meal (no more food allowed after this) 18.00 Stomach fully emptied 22.00 Pudding formulation 4 15 mins 6.00 am - day of examination Pudding formulation 4 15 mins 8.00 Patient fasts - no liquids 10.00 Colonoscopy Examination

(Preliminary) Patient Instructions:

[0280] Start the pre-colonoscopy preparation the day before your colonoscopy, with a low residue meal at lunchtime12.00 m (see below for more information). [0281] From the moment you start the preparation, only clear liquids can be drunk (and nothing coloured red or purple), and no food can be consumed after your no residual meal at lunchtime. [0282] Begin the bowel cleansing formulation at 22.00. Take one pot of the pudding (68 g) out of the fridge and consume with one glassful of water (250 ml). It is important that all 250 ml of water is consumed. After 15 minutes, so at 22.15, take another pot of pudding out of the fridge and consume this slowly with one glassful of water (250 ml). Continue this process, repeating every 15 minutes, until you have eaten all 4 pots (finishing at 23.00). [0283] Ideally the liquid taken with the pudding is 250 ml of cold mineral water, however the water can be substituted for another clear, cold liquid (but no cola and nothing carbonated). [0284] Repeat this process at 6.00 am the day of your colonoscopy, consuming all 4 pots of pudding slowly at intervals of 15 minutes (finishing at 7.00), again consuming each pot with 250 ml of (ideally) cold mineral water. [0285] From 8.00, no further liquids can be consumed. [0286] 10.00 colonoscopy procedure begins.

[0287] Low residue meal is a meal that is low in fibre and other undigested materials to minimise the production of solid waste in your colon and rectum. Examples include: Skinless chicken, fish, eggs, white bread, pasta, white rice, canned or cooked vegetables (without skin or seeds), broth-based soups, honey, jelly (McCray and Balaban, 2007). Unfortunately, your bowel preparation will likely be unpleasant. However, if you do it correctly and follow all instructions, then the colonoscopy will be able to be completed fully and successfully. If your bowel cleansing is not adequate (i.e. there is still solid and liquid stool matter in the bowel), then the procedure will have to be repeated, causing further discomfort. It is in your best interests that you follow all instructions closely.

Example 10

[0288] Clinical Pilot Study with a Composition as Described in Example 3

[0289] This pilot study was aimed at evaluating the effect of a new formulation type of bowel preparation before colonoscopy.

[0290] At present, most bowel preparations consist of medium to large volume intake of a solution of Poly-Ethylene-Glycol with various salts or more concentrated low volume intake of the same compounds followed by large quantities of clear fluids. Many patients find the taste of these cleansing remedies somewhat problematic and, thus, difficult to drink.

[0291] The new edible formulation of cleansing product according to the present invention is an attempt to alleviate the taste, volume, as well as the texture of the cleansing solution.

Material and Methods:

[0292] Ten healthy male volunteers (age 22-49 years) received the preparation. We maintained a standard split dose regimen with no food intake starting 24 hours prior to colonoscopy, but with an intake of clear fluid of at least 250 mL per hour. Approximately, 4 hours after the final intake of the cleansing product a colonoscopy was performed. The quality of cleansing was estimated using the Boston Bowel Preparation Scale (BBPS).

Results

[0293] The volunteers had cleansing BBPS scores at seven or above.

Conclusion

[0294] It is possible to cleanse the bowel with our new product sufficiently for performance of screening colonoscopy.

Keywords

[0295] Boston Bowel Preparation Scale (BBPS), Bowel Preparation, Cleansing, Colonoscopy

Introduction

[0296] Colonoscopy is the preferred procedure for detecting pathology in the large bowel. The validity of the procedure depends upon the degree of cleansing.

[0297] Several factors influence the degree of cleansing such as the volume of the preparation, the active agents of the preparation, compliance of the patients, etc. (1).

[0298] We have in this context chosen to try to augment the probability of compliance by changing the taste and texture of the cleansing product. In our edible product, the cleansing agents are embedded in a gel with a creamy consistency and the taste has been improved by addition of vanilla and prune extracts. Furthermore, powdered ascorbic acid was supplied for optional sprinkling on top of the product.

[0299] The quality of the product rely on the results as judged by colonoscopy, we therefore as a first attempt have given our preparation to volunteers and in the following, we describe our findings.

Methods and Materials

[0300] A batch of cleansing preparation was manufactured (130 portions of 68.2 gram, containing Polyethylene Glycol 3350, Lactulose powder, Potassium Chloride, Sodium Citrate-dihydrate, Calcium Carbonate, Vanillin, Carragenan, Carob, and Prune concentrate. Manufacturer: HB-medical). Each cleansing procedure consisted of a 24-hour fasting period with unlimited access to clear fluids with a minimal intake of 250 mL/hour when awake. At 8:00 pm the evening before the procedure, the volunteers ingested the first four portions of the preparation with a time space of 15 minutes between each portion. The next four portions were taken in the same sequence on the day of the examination starting four hours prior to the procedure. Each cleansing, thus, comprised of eight portions of the preparation in total.

[0301] Four hours after the last intake of the product a colonoscopy was performed. All endoscopies were performed by a single endoscopist, who had performed more than 5000 endoscopies. The quality of the cleansing was evaluated by using the Boston Bowel Preparation Scale (2). The endoscopist followed the guidelines put forward in the instructional video available at the site of the Boston University, School of Medicine. Colonoscopies were performed in the Endoscopy unit at the Zeeland University Hospital using Olympus Exera 3 CF-HQ190L colonoscopes with a UPD-device.

[0302] Ten healthy male volunteers (age 22 to 49 years) were included.

[0303] All volunteers were offered sedation with Fentanyl 50 g i.v. supplemented with Midazolam 2 mg i.v.

Results

[0304] All the included volunteers had followed the instructions for cleansing. When asked three volunteers reported slight bloatedness after the first four portions of the product, otherwise no unpleasant effects were reported. They all had a complete colonoscopy performed without side effects or complications. No pathological findings were seen. The results of the Boston Bowel Preparation Scale are shown in FIG. 8.

Conclusion

[0305] This small pilot study shows that it is possible to cleanse the large bowel with our new edible preparation and the quality of the cleansing seems appropriate for performing screening colonoscopy. This study does not give any clues as to whether patients may prefer our product to other preparations, but future investigations should be performed to show whether our product is a reasonable alternative to already existing cleansing products.

REFERENCES

[0306] 1. John R. Saltzman et al. Bowel preparation before colonoscopy. Gastrointest Endosc 2015; 81, 4:781-94 (Guideline from the American Society of Gastrointestinal Endoscopy) [0307] 2. Edwin J. Lai et al. The Boston bowel preparation scale: a valid and reliable instrument for colonoscopy-oriented research. Gastrointest Endosc 2009; 69:620-5.