AU2007335255A1

AU2007335255A1 - Composition and method for treatment of IBS

Info

Publication number: AU2007335255A1
Application number: AU2007335255A
Authority: AU
Inventors: David Lubowski
Original assignee: Individual
Current assignee: Individual
Priority date: 2006-12-20
Filing date: 2007-12-19
Publication date: 2008-06-26
Also published as: WO2008074080A1

Description

WO 2008/074080 PCT/AU2007/001968 -1 TITLE: COMPOSITION AND METHOD FOR TREATMENT OF IBS TECHNICAL FIELD 5 The invention relates to compositions and methods for the treatment of irritable bowel syndrome (IBS) or the amelioration of symptoms thereof. BACKGROUND 10 The precise prevalence of irritable bowel syndrome (IBS) is unknown, but it is undoubtedly a very common condition and a common reason for visits to the general practitioner as well as specialist gastroenterologist and surgeon. The condition causes a number of symptoms which occur alone or in various 15 combinations. Abdominal bloating, pain, flatulence (wind), diarrhea, or constipation (or intermittent bouts of both) may all occur. In some cases pain is intermittently very severe and can lead to time off work. It may begin at a young age, not uncommonly in the late teens, but may also 20 occur later in life. In some cases it mysteriously burns out and symptoms resolve, but in other cases it may persist for many years or may even be a life-long condition. IBS is more common in women than men. The extent of bloating may vary during the day, and it not uncommon for young 25 female patients to complain that by the end of the day they appear as though they are pregnant. Some patients need to loosen or re-tighten their clothing during the day as swelling changes. Constipation may be mild or severe. Using colon transit studies, transit time 30 through the colon is found to be normal in IBS, which distinguishes the condition from other forms of constipation. Diarrhoea may also vary in severity, and varies from day to day.

WO 2008/074080 PCT/AU2007/001968 -2 The cause and pathophysiology of IBS remains unclear. The bowel has been shown to be particularly sensitive to distension and this may be one of the mechanisms causing pain. The presence of contrary symptoms, such as constipation and diarrhea occurring in the same condition, or even intermittently in the same patient, underscores 5 the lack of understanding of the condition. Many forms of treatment have been tried for IBS. Conventional medications for treatment of constipation (ie laxatives) or diarrhoea (anti-diarrhoeal medications) are used to treat these facets of the condition. However, other manifestations such as pain, 10 flatulence and bloating are particularly difficult to treat. Anti-spasmodic drugs such as Buscopan and Colofac are commonly used. Peppermint has also been shown to be effective for IBS in a number of studies. There are a number of proprietary formulations of peppermint oil capsules on the 15 market. These capsules typically contain 0.2 ml of peppermint in an enteric coated capsule for release of the peppermint in the intestine (rather than in the stomach). This represents a standardised dose that can be readily taken at any time. Compliance with treatment with peppermint capsules is usually very good. 20 Fennel and ginger are also known to relieve symptoms such as bloating, flatulence and pain. Fennel is most readily available as a fresh herb. Ginger is available in many forms, either natural or sweetened. Fresh fennel is taken most conveniently with a meal at home, however, this is difficult to achieve for patients who work or who are away from home. Even while at home it may not be convenient to take fennel or 25 ginger other than when the patient remembers to do so, or is sitting down to a formal meal. Also, under those circumstances, it can be difficult to achieve a standardised dosage of ginger or fennel. There remains the need for further treatment of IBS and/or symptoms thereof. 30 Any discussion of the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of common general knowledge in the field.

WO 2008/074080 PCT/AU2007/001968 -3 SUMMARY OF THE INVENTION According to a first aspect, the invention provides a composition for the 5 treatment of irritable bowel syndrome (IBS) including a combination of a therapeutic dose of peppermint, a therapeutic dose of fennel and a therapeutic dose of ginger. In another aspect, the invention provides a composition for the amelioration of one or more symptoms of irritable bowel syndrome (IBS) including a combination of a 10 therapeutic dose of peppermint, a therapeutic dose of fennel and a therapeutic dose of ginger. Preferably the symptoms of IBS include, but are not limited to, one or more of bloating, flatulence or pain. The symptoms may be a combination of bloating and 15 flatulence, a combination of bloating and pain or a combination of flatulence and pain. The symptoms may also be a combination of bloating, flatulence and pain. Preferably, the peppermint is administered in a therapeutically effective amount up to an amount equivalent to 50 ml of peppermint oil. More preferably, the peppermint 20 is administered in a dose equivalent to 200-250 mg of peppermint oil. Most preferably, the peppermint is administered as 200-250 mg of peppermint oil Preferably, the ginger is administered in a therapeutically effective amount up to an amount equivalent to 50 ml of ginger oil. More preferably, the ginger is administered 25 in a dose equivalent to 100-150 mg of ginger oil. Most preferably, the ginger is administered as 100-150 mg of ginger oil. Preferably the fennel is administered in a therapeutically effective amount up to an amount equivalent to 50 ml of fennel oil. More preferably the fennel is administered 30 in a dose equivalent to 100-150 mg of fennel oil. Most preferably the fennel is administered as 100-150 mg of fennel oil. In the present invention. It is preferable that the dosage includes, in independently variable amounts, peppermint in an amount equivalent to 200-250 mg of WO 2008/074080 PCT/AU2007/001968 -4 peppermint oil, ginger in an amount equivalent to 100-150 mg of ginger oil and fennel oil in an amount equivalent to 100-150 mg of fennel oil. More preferably the dosage includes, in independently variable amounts, 200-250 mg of peppermint oil, 100-150 mg of ginger oil and 100-150 mg of fennel oil. One highly preferred embodiment is in the 5 form of a 500 mg dosage form including 200 mg peppermint oil, 150 mg ginger oil and 150 mg fennel oil. In one preferred embodiment, the compositions of the present invention are provided in the form of a capsule, which may be an enteric capsule or a capsule suitable 10 for release in the stomach. More preferably, the compositions are provided in the form of an enteric coated capsule. In an alternative preferred embodiment, the compositions of the present invention are provided in the form of a syrup. 15 It is preferred in the compositions of the present invention that the weight ratio of peppermint oil:ginger oil: fennel oil is from around 1.33:1:1 to around 2.5:1:1, although any ratio which meets the criteria set forth previously for therapeutic efficacy of each component is acceptable. 20 In an alternative embodiment, the peppermint, ginger and fennel may be present as dry ingredients. In that case, it is preferred that the dry ingredients are each present in a therapeutically effective amount, up to an amount equivalent to 50 ml of peppermint oil, ginger oil or fennel oil. 25 Preferably the dry peppermint is administered in a dose equivalent to 200-250 mg of peppermint oil. Preferably the dry ginger is administered in a dose equivalent to 100-150 mg of ginger oil. Preferably the dry fennel is administered in a dose equivalent to 100-150 mg of fennel oil. 30 In one dry dosage form, the dry ingredients are blended in the form of a desiccated powder. Alternatively, the dry ingredients may be compressed into a tablet.

WO 2008/074080 PCT/AU2007/001968 -5 The formulations of the present invention may also include one or more additional substances efficacious in treating IBS, or one or more additional substances efficacious in treating one or more symptoms of IBS. For preference, these substances may be selected from:Yarrow (achillea millefolium), Witch Hazel (hamamelis 5 virginiana), Horsetail (equiseti herba), and Aloe vera species. In another broad aspect, the invention provides a method of treating IBS including the step of administering to a subject in need thereof a composition according to the present invention. 10 In another aspect, the invention provides a method of treating one or more symptoms of IBS including the step of administering to a subject in need thereof a composition according to the present invention. In one particular aspect, the invention provides a method of treating either alone or in combination, any of bloating flatulence 15 or abdominal pain including the step of administering to a subject in need thereof a composition according to the present invention. The peppermint, ginger and fennel are all present in a therapeutically effective amount. In another aspect, the invention provides the use of a combination of peppermint, 20 ginger and fennel for the manufacture of a medicament for the treatment of IBS. In another aspect, the invention provides the use of a combination of peppermint, ginger and fennel for the manufacture of a medicament for the treatment of one or more symptoms of IBS. In one particular aspect, the invention provides the use of a 25 combination of peppermint, ginger and fennel for the manufacture of a medicament for the treatment of, either alone or in combination, any of bloating, flatulence or abdominal pain. The peppermint, ginger and fennel are all present in a therapeutically effective amount. 30 In yet another aspect, the invention provides a method of increasing patient compliance with a course of ginger and fennel including the step of formulating ginger and fennel with peppermint prior to administering the combination of peppermint, ginger and fennel to the patient.

WO 2008/074080 PCT/AU2007/001968 -6 In yet another aspect, the invention provides a method of increasing patient compliance and increasing efficacy against IBS or symptoms thereof of a course of ginger and fennel including the step of formulating ginger and fennel with peppermint 5 prior to administering the combination of peppermint, ginger and fennel to the patient. In yet another aspect, the invention provides a method for the treatment of IBS or the amelioration of the symptoms thereof comprising administering to a subject in need thereof a combination of a therapeutically effective amount of peppermint, a 10 therapeutically effective amount of fennel and a therapeutically effective amount of ginger. Ideally, the peppermint, fennel and ginger are administered simultaneously, either in a single dose. However, equally effectively, they may be administered in the form of individual dosage forms of each substance taken together at the same or substantially the same time. 15 Also, whilst the invention is described with reference to simultaneous or substantially simultaneous administration, the invention also encompasses the administration of the three substances at staggered intervals, with a view to achieving the synergistic benefits of the interaction of the three compounds. 20 Accordingly, the invention also provides a method of treating IBS including the step of administering to a subject in need thereof a combination of a therapeutic dose of peppermint, a therapeutic dose of fennel and a therapeutic dose of ginger. 25 A clinician would, if necessary, readily be able to adjust the dosages and ratios as provided above, to compensate for non-simultaneous ingestion of one or more of the peppermint, fennel or ginger. Non simultaneous ingestion may be required if one or more of the substances is not well tolerated. 30 WO 2008/074080 PCT/AU2007/001968 -7 DESCRIPTION The invention relates to the administration of compositions including therapeutically effective amounts of peppermint, ginger and fennel to IBS sufferers for 5 the treatment of IBS or the amelioration of the symptoms of IBS. Whilst each of these compositions has been used individually in IBS treatments, it has not been known before to simultaneously administer therapeutically effective amounts of all three. Generally, a therapeutic amount of peppermint, fennel or ginger 10 would be regarded as 50 mg (or 0.05 ml of peppermint, ginger or fennel oil). A therapeutic amount of peppermint is more preferably in the region of 200-250 mg of peppermint oil, or an equivalent amount of active ingredients obtained from, for example, fresh or dried peppermint. Therapeutic amounts of ginger and fennel have been found to be more preferably in the region of 100-150 mg of ginger or fennel oil 15 respectively, or an equivalent amount of actives obtained from fresh or dried product. A number of formulations of peppermint are available which contain additional agents, but these additional agents are often present in sub therapeutic amounts, or in non-standardised doses. Herbal remedies for example usually contain numerous active 20 agents or potentially active agents, however, the dosages are non standard and often in sub therapeutic quantities. The compounds need to be administered not only in therapeutic amounts, but also substantially together. Ideally, this is in the form of a single dose which has all 25 three, but it could be that therapeutic amounts of each are taken individually at the same time, or multiple smaller doses are taken at the same time. A person of ordinary skill in the art would easily be able to determine any combination of dosages and amounts which ensure that the desired simultaneous loading of all three components was achieved. 30 One particularly preferred dosage form is a capsule that provides 200 mg peppermint oil, 150 mg ginger oil and 150 mg fennel oil.

WO 2008/074080 PCT/AU2007/001968 Another highly preferred dosage form is a capsule that provides about 2 50mg peppermint, about 150 mg of ginger and about 100 mg of fennel. The weight of the actives is about 500mg in total. The dosage form may also contain other excipients, such as stabilizers and the like in amounts as dictated by the formulation. Typically, 5 these would amount to less than 0.05 ml. Multiple tablets or capsules of smaller amounts could be used, eg two tablets having 100 mg peppermint, 75 mg ginger and 75 mg fennel, however these suffer from the drawback that if a single tablet is taken, which is possible for patients looking to 10 extend their supply of medication, the dosage loadings will be sub-therapeutic. The compositions of the present invention can be administered once, twice or three times a day at an appropriate spacing, or as otherwise directed by the physician. The dosages need to be formulated bearing in mind that the critical therapeutically effective 15 loading of each dosage needs to be applied at each administration. A course of tablets where peppermint, ginger and fennel were administered in spaced apart doses where for example 200 mg peppermint, 100 mg fennel and 100 mg ginger were administered in total over three equally spaced apart doses would not be expected to provide the benefits of the present invention, since at no time was any effective therapeutic loading achieved. 20 The physician may also choose to increase the dosage of any or all of the components, typically in the range 0.5 to 50 ml oil or an equivalent of fresh or dried material. 25 However, at each administration, it is important to get the appropriate therapeutically effective loading of all three components. The dosage form most preferred is a capsule containing a mixture of all three components, as outlined above. Any suitable conventional capsule forms may be used. 30 Enteric capsules are preferred. However, delivery methods other than a capsule may also be used. The composition may be in the form of syrup, that is a liquid, which has been flavoured in WO 2008/074080 PCT/AU2007/001968 -9 such a way as to allow the combination to be administered by mouth. Again, the syrup would contain dosages of the active agents equivalent in dosage to the amounts described above. 5 Alternatively, the dosage form may be in powdered form in a container or sealed package, where each component is a desiccated powder. The amount of each component is standardised, and is equivalent in dosage to the amounts described above. Alternatively, the dry components may also be compressed into a tablet. Oil 10 components may be mixed with a dry inert matrix agent for compression into a tablet. Although less preferred, the components may also be presented to the patient in the form of a food, for example, a cookie or food bar or a drink, shake or similar. 15 The formulations may also be expressed in terms of the ratio of components. Preferred ratios of peppermint:ginger:fennel are: 2:1:1, 2:1:1.5, 2:1.5:1.5, 2:1.5:1, 2.5:1:1, 2.5:1:1.5, 2.5:1.5:1.5, 2.5:1.5:1. It needs to be borne in mind that in addition to these ratios, a therapeutically effective amount of each component needs to be added. 20 In addition to peppermint, ginger and fennel, the present invention may also include other substances which may be efficacious in treating IBS including Yarrow (achillea millefolium), Witch Hazel (hamamelis virginiana), Horsetail (equiseti herba), and Aloe vera species. 25 The present applicant has observed that a combination of fennel, ginger and peppermint, taken at the same time, provides an effective treatment for bloating, flatulence and pain in some patients. The combination of fennel, ginger and peppermint is more effective than 30 peppermint alone, and is more effective than ginger and fennel alone.

WO 2008/074080 PCT/AU2007/001968 -10 It has also been observed that compliance with formulations containing peppermint is generally very good, much better than compliance with ginger and fennel, which, in whatever form, is generally quite poor. 5 In the present case, the combination of peppermint with ginger and fennel generally results in high levels of compliance. CLINICAL STUDIES 10 26 Patients with symptoms of irritable bowel syndrome (IBS) were treated with a combination of peppermint, ginger, and fennel in accordance with the present invention. Patients had various symptoms including abdominal pain, bloating, distension, and flatulence ("wind"). 15 Patients were asked to use 0.2ml peppermint capsules, one square piece of ginger, and an equivalent amount of fennel. The dosages of ginger and fennel administered were not quantified in more detail, but should generally ensure that therapeutic amounts of each substance were consumed. 20 24 Patients from the group could be contacted and were followed up at a suitable time either at their visit or by telephone. The patients were asked about improvements or changes in pain, bloating, wind, and abdominal distension. Diarrhoea was not assessed since this symptom, although not infrequent in patients with IBS, is affected by 25 multiple other factors including other medications. 17 (71%) Patients had partial or significant improvement in symptoms. 12 Patients had improvement in pain, 3 patients had improvement in bloating and wind, and 2 had improvement in pain and bloating. Seven (29%) were not improved, with 30 symptoms continuing as before. No patient had worsening of symptoms during the follow-up period.

WO 2008/074080 PCT/AU2007/001968 - 11 More than two thirds of patients reported an improvement in symptoms with combinations of peppermint, ginger and fennel. As there is currently no approved treatment which reliably improves symptoms of IBS, achieving improvements in 71% of patients is considered a very good outcome. 5 Compliance with treatment was not quantified in the follow-up audit, so it is unknown whether patients reliably took all three substances. However, it seems that compliance with the use of peppermint and ginger is more reliable than the use of fennel as a result of the more ready availability. 10 Some patients did not tolerate raw ginger, which is generally less palatable than sugar-coated ginger. Patients were encouraged to take sugar-coated ginger if desired. The high levels of patient compliance and high efficacy of the composition of the 15 present invention means that the combination of therapeutically effective amounts of fennel, ginger and peppermint has been found to be unusually effective in the treatment of IBS and the symptoms thereof

Claims

1. A composition for the treatment of irritable bowel syndrome IBS including a combination of a therapeutic dose of peppermint, a therapeutic dose of fennel and a 5 therapeutic dose of ginger.

2. A composition for the amelioration of one or more symptoms of irritable bowel syndrome IBS including a combination of a therapeutic dose of peppermint, a therapeutic dose of fennel and a therapeutic dose of ginger. 10

3. A composition according to claim 2 wherein the one or more symptoms is one or more of bloating, flatulence or pain.

4. A composition according to claim 3 wherein the one or more symptoms are a 15 combination of bloating and flatulence, a combination of bloating and pain or a combination of flatulence and pain.

5. A composition according to claim 1 wherein the one or more symptoms of are a combination of bloating, flatulence and pain. 20

6. A composition according to any one of the preceding claims wherein the peppermint is administered in a therapeutically effective amount up to an amount equivalent to 50 ml of peppermint oil. 25 7. A composition according to claim 6 wherein the peppermint is administered in a dose equivalent to 200-250 mg of peppermint oil

8. A composition according to claim 7 including 200-250 mg of peppermint oil 30 9. A composition according to any one of the preceding claims wherein the ginger is administered in a therapeutically effective amount up to an amount equivalent to 50 ml of ginger oil. WO 2008/074080 PCT/AU2007/001968 - 13 10. A composition according to claim 9 wherein the ginger is administered in a dose equivalent to 100-150 mg of ginger oil

11. A composition according to claim 10 including 100-150 mg of ginger oil. 5

12. A composition according to any one of the preceding claims wherein the fennel is administered in a therapeutically effective amount up to an amount equivalent to 50 ml of fennel oil. 10 13. A composition according to any one of the preceding claims wherein the fennel is administered in a dose equivalent to 100-150 mg of fennel oil.

14. A composition according to claim 10 including 100-150 mg of fennel oil. 15 15. A composition according to any one of the preceding claims wherein the dosage includes in independently variable amounts peppermint in an amount equivalent to 200 250 mg of peppermint oil, ginger in an amount equivalent to 100-150 mg of ginger oil and fennel oil in an amount equivalent to 100-150 mg of fennel oil. 20 16. A composition according to claim 15 wherein the dosage includes in independently variable amounts 200-250 mg of peppermint oil, 100-150 mg of ginger oil and 100-150 mg of fennel oil.

17. A composition according to claim 16 in the form of a 500 mg dosage form 25 including 200 mg peppermint oil, 150 mg ginger oil and 150 mg fennel oil.

18. A composition according to any one of the preceding claims in the form of a capsule. 30 19. A composition according to claim 18 in the form of an enteric coated capsule.

20. A composition according to any one of claimsl-17 in the form of a syrup. WO 2008/074080 PCT/AU2007/001968 -14

21. A composition according to any one of the preceding claims wherein the weight ratio of peppermint oil:ginger oil: fennel oil is 1.33:1:1.

22. A composition according to claim 21 wherein the weight ratio of peppermint 5 oil:ginger oil: fennel oil is 2.5:1:1

23. A composition according to any one of claims 1 to 5 wherein the peppermint, ginger and fennel are present as dry ingredients. 10 24. A composition according to claim 23 wherein the dry ingredients are each present in a therapeutically effective amount, up to an amount equivalent to 50 of peppermint oil, ginger oil or fennel oil.

25. A composition according to claim 24 wherein the dry peppermint is administered 15 in a dose equivalent to 200-250 mg of peppermint oil

26. A composition according to any one of claims 24-25 wherein the dry ginger is administered in a dose equivalent to 100-150 mg of ginger oil 20 27. A composition according to any one of claims 24-26 wherein the dry fennel is administered in a dose equivalent to 100-150 mg of fennel oil

28. A composition according to any one of claims 23-27 wherein the dry ingredients are blended in the form of a desiccated powder 25

29. A composition according to any one of claims 23-28 wherein the dry ingredients are compressed into a tablet.

30. A composition according to any one of the preceding claims including one or 30 more additional substances efficacious in treating IBS.

31. A composition according to any one of the preceding claims including one or more additional substances efficacious in treating one or more symptoms of IBS. WO 2008/074080 PCT/AU2007/001968 - 15 32. A composition according to claim 30 or 31 wherein the additional substances are selected from:Yarrow (achillea millefolium), Witch Hazel (hamamelis virginiana), Horsetail (equiseti herba), and Aloe vera species. 5

33. A method of treating IBS including the step of administering to a subject in need thereof a combination of a therapeutic dose of peppermint, a therapeutic dose of fennel and a therapeutic dose of ginger. 10 34. A method of treating IBS including the step of administering to a subject in need thereof a composition according to any one of claims 1 to 32.

35. A method of treating one or more symptoms of IBS including the step of administering to a subject in need thereof a composition according to any one of claims 15 1to32.

36. A method of treating bloating including the step of administering to a subject in need thereof a composition according to any one of claims 1 to 32. 20 37. A method of treating flatulence including the step of administering to a subject in need thereof a composition according to any one of claims 1 to 32.

39. A method of treating abdominal pain including the step of administering to a subject in need thereof a composition according to any one of claims 1 to 32. 25

40. The use of a combination of peppermint, ginger and fennel for the manufacture of a medicament for the treatment of IBS.

41. The use of a combination of peppermint, ginger and fennel for the manufacture 30 of a medicament for the treatment of one or more symptoms of IBS.

42. The use of a combination of peppermint, ginger and fennel for the manufacture of a medicament for the treatment of bloating. WO 2008/074080 PCT/AU2007/001968 -16

43. The use of a combination of peppermint ginger and fennel for the manufacture of a medicament for the treatment of flatulence. 5 44. The use of a combination of peppermint ginger and fennel for the manufacture of a medicament for the treatment of abdominal pain.

45. The use according to any one of claims 40 to 44 wherein the peppermint, ginger and fennel are all present in a therapeutically effective amount. 10

46. A method of increasing patient compliance with a course of ginger and fennel including the step of formulating ginger and fennel with peppermint

47. A method of increasing patient compliance and increasing efficacy of a course of 15 ginger and fennel including the step of formulating ginger and fennel with peppermint.

48. A capsule including about 250 mg peppermint oil, about 150 mg ginger oil and about 100 ing fennel oil. 20 49. A capsule according to claim 46 including one or more excipients such as stabilizers and the like.