GB2371983A - Compositions to treat irritable bowel syndrome - Google Patents

Compositions to treat irritable bowel syndrome Download PDF

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Publication number
GB2371983A
GB2371983A GB0103328A GB0103328A GB2371983A GB 2371983 A GB2371983 A GB 2371983A GB 0103328 A GB0103328 A GB 0103328A GB 0103328 A GB0103328 A GB 0103328A GB 2371983 A GB2371983 A GB 2371983A
Authority
GB
United Kingdom
Prior art keywords
medicament
piperazine
bowel syndrome
irritable bowel
piperazine phenothiazine
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
GB0103328A
Other versions
GB0103328D0 (en
Inventor
Mark Coke
Peter William Dettmar
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Reckitt Benckiser Healthcare UK Ltd
Original Assignee
Reckitt and Colman Products Ltd
Reckitt Benckiser Healthcare UK Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Reckitt and Colman Products Ltd, Reckitt Benckiser Healthcare UK Ltd filed Critical Reckitt and Colman Products Ltd
Priority to GB0103328A priority Critical patent/GB2371983A/en
Publication of GB0103328D0 publication Critical patent/GB0103328D0/en
Publication of GB2371983A publication Critical patent/GB2371983A/en
Withdrawn legal-status Critical Current

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Classifications

    • 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
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/5415—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • 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

Abstract

The invention relates to the use of piperazine phenothiazine, a piperazine phenothiazine derivative or a salt thereof, for the treatment of irritable bowel syndrome. The preferred piperazine phenothiazine derivative is prochlorperazine maleate, and the use of fluphenazine is also exemplified.

Description

Compositions This invention relates to the preparation of medicaments for the treatment of irritable bowel syndrome more particularly to the use of particular phenothiazine derivatives for the preparation of such medicaments.
Irritable bowel syndrome (IBS) is a functional disorder of the gut that is defined in terms of symptoms.
It is characterised primarily by bowel habit alteration, abdominal pain and bloating, although many other symptoms may also be present. IBS has also been known as mucous colitis and spastic or irritable colon. There is no one generally agreed cause of IBS although a number of factors have been identified as triggers, including gastroenteritis, food intolerance and stress.
IBS is a chronic problem in many countries, for example in the USA an estimated 14 to 22% of the population suffer from various degrees of the condition.
The condition can vary in its effect on the sufferer from a short, but very unpleasant, episode to a long term seriously debilitating condition.
Many approaches have been suggested for the treatment of IBS, including fibre supplementation and the use of anticholinergic or antispasmodic agents, but scientific trials documenting their efficacy are rare.
Part of the problem caused by IBS is the interruption of daily routine caused by the symptoms, e. g. pain, altered bowel habit or nausea, which can lead to further stress or even psychological difficulties.
Thus a reduction in these particular symptoms would be considered most particularly beneficial.
We have now found a group of pharmaceutical agents which we believe are particularly useful in treating some or all of the symptoms of IBS.
According to a first aspect of the present invention there is provided the use of piperazine phenothiazine, a piperazine phenothiazine derivative, or a salt thereof, for the preparation of a medicament for the treatment of irritable bowel syndrome.
Piperazine phenothiazine derivatives are defined as compounds of the Formula I
wherein Ri contains a piperazine group ; and
R2 is selected from hydrogen, chlorine, CF3, COCH3, OCH3, CN, COCH2CH3'COCH2CH2CH3, SCH3, SCH2CH3, SO2CH3 and SO2N (CH3) 2.
Preferably the piperazine phenothiazine derivatives used in the medicaments of the invention are selected from compounds of formula I wherein Rl is
and R3 is CH2CHRsCH2 ; Rs is selected from hydrogen and CH3 ; R4 is CH3 or CH2CH2OR6 ; and R6 is hydrogen, COCH3 or CH2CH2OH.
More preferably the piperazine phenothiazine derivatives used in the medicaments of the invention are selected from acetophenazine, butaperazine, carphenazine, dixyrazine, fluphenazine, perazine, perphenazine, prochlorperazine, thiethylperazine, thiopropazate, thioproperazine and trifluoperazine, or salts thereof.
Most preferably the piperazine phenothiazine derivative is prochlorperazine or a salt thereof, e. g. prochlorperazine maleate.
Mixtures of piperazine phenothiazine and/or one or more piperazine phenothiazine derivatives may be used in the preparation of the medicaments of the invention.
In a preferred embodiment of this aspect to the invention, there is provided the use of prochlorperazine, or a salt thereof, for the preparation of a medicament for the treatment or irritable bowel syndrome.
Preferably the medicament prepared according to this aspect of the present invention is a transdermal, oral, buccal or sublingual medicament.
According to a second aspect to the present invention, there is provided the use of piperazine phenothiazine, a piperazine phenothiazine derivative (preferably prochlorperazine) or a salt thereof, for the treatment of irritable bowel syndrome.
The dosage of piperazine phenothiazine or the derivative thereof that may be used for the treatment of IBS will depend upon the toxicology of the active agent and the severity of the symptoms. However, doses of from 0.1 to 100 mg (more preferably 0.5 to 30 mg) from 1 to 4 times daily will be preferred.
According to a further aspect to the present invention there is provided a medicament for the treatment of irritable bowel syndrome, the medicament including a pharmaceutically effective amount of piperazine phenothiazine, a piperazine phenothiazine derivative or a salt thereof.
The preferred medicaments of the invention comprise from 0.1 to 100 mg of piperazine phenothiazine or a derivative thereof, more preferably 0.5 to 30 mg.
As such, the medicament may contain from 0.1 to 50% weight for weight (w/w) of the piperazine phenothiazine or derivative thereof, more preferably 1 to 20% w/w, most preferably 4 to 10% w/w, the balance of the medicament comprising pharmaceutically acceptable carriers, diluents or excipients.
The medicament of the invention will be particularly useful for the treatment of the nausea and pain associated with IBS.
The medicaments of the invention may be administered to patients by any suitable route including oral, buccal, sublingual, rectal, transdermal, parenteral and intramuscular administration. Preferably they are administered transdermally, orally, buccally or sublingually.
The medicaments of the invention may be in any suitable dosage form depending upon the route of administration to be used including tablets, granules, capsules, transdermal patches, suppositories, injections, buccal tablets or sublingual tablets.
Preferably the medicaments of the invention are in the form of transdermal patches, oral tablets, buccal or sublingual tablets.
The medicaments of the invention may comprise any pharmaceutically acceptable other ingredients depending upon the dosage form, for example granulating agents, tableting agents, flavours, colours etc.
Where the medicaments of the invention are in the form of buccal tablets they preferably comprise at least one monosaccharide or disaccharide and one or more gums e. g. xanthan and/or locust bean gum.
The medicaments of the invention may be produced by any conventional methods depending upon the dosage form.
In a preferred embodiment of this aspect to the present invention there is provided a medicament for the treatment of irritable bowel syndrome, the medicament containing: i) 1 to 20% w/w prochlorperazine or a salt thereof ; ii) 80 to 99% w/w pharmaceutically acceptable carriers, diluents, excipients granulating agents, tableting agents, flavours (including monosaccharides and/or disaccharides) and colours; and iii) optionally 0.1 to 15% w/w gums (for example xanthan and/or locust bean gum).
According to a further aspect to the present invention there is provided a pack for the treatment of irritable bowel syndrome including: i) piperazine phenothiazine, a piperazine phenothiazine derivative or a salt thereof; and ii) instructions for the use thereof in the treatment of irritable bowel syndrome.
Preferably the piperazine phenothiazine, derivative thereof or salt thereof is included in a medicament.
The invention will now be illustrated by the following examples.
Example 1 Oral tablets are prepared having the following composition mg per tablet Prochlorperazine maleate 5.0 Crospovidone 5.0 Polyvinyl pyrrolidone 5. 0 Talc 1.0 Magnesium stearate 0.5 Lactose, anhydrous 83.5 1. The prochlorperazine maleate, polyvinylpyrrolidone and lactose are mixed in a high speed mixer granulator.
2. The powder is granulated by high speed mixing with the addition of isopropanol.
3. The granules are dried in a tray oven at 40 to 60 C for 25 to 40 minutes.
4. The granules are screened to remove large aggregates and blended with the crospovidone, talc and magnesium stearate.
5. The mixed powder and granules are compressed to form 100 mg tablets on a conventional tablet press.
Doses of two tablets according to Example 1 may be administered three times daily for the treatment of IBS.
Example 2 The tablets of Example 1 may be repeated replacing the prochlorperazine maleate with fluphenazine (5mg per tablet).
Example 3 Buccal tablets are prepared having the following composition: mg per tablet Xanthan gum 1.5 Locust bean gum 1.5 Prochlorperazine maleate 5.0 Polyvinylpyrrolidone 3.0 Sucrose 47.5 Magnesium stearate 0.5 talc 1.0 1. All of the components except the talc and magnesium stearate are blended together with a high speed mixer granulator.
2. The mixed powders are granulated using isopropanol.
3. The granules are dried at 50 C in a tray oven and then passed through a 500 urn sieve. 4. The granules are blended with the talc and magnesium stearate and compressed into 5.56 mm diameter tablets of 60 mg weight.
One tablet according to Example 3 may be placed in the buccal cavity and allowed to dissolve, up to 3 times daily, for use in the treatment of IBS.

Claims (14)

  1. Claims 1. The use of piperazine phenothiazine, a piperazine phenothiazine derivative, or a salt thereof, for the preparation of a medicament for the treatment of irritable bowel syndrome.
  2. 2. The use as claimed in Claim 1 wherein the piperazine phenothiazine derivative is selected from compounds of the Formula I
    wherein Ri contains a piperazine group; and R2 is selected from hydrogen, chlorine, CF3, COCH3, OCH3, CN, COCH2CH3'COCH2CH2CH3, SCH3, SCH2CH3, SO2CH3 and SO2N (CH3) 2.
  3. 3. The use as claimed in Claim 2 wherein R, is
    and
    R3 is CH2CHR5CH2 ; Rs is selected from hydrogen and CH3 ; R4 is CH3 or CH2CH2OR6 ; and R6 is hydrogen, COCH3 or CH2CH2OH.
  4. 4. The use as claimed in any of Claims 1 to 3 wherein the piperazine phenothiazine derivative is selected from acetophenazine, butaperazine, carphenazine, dixyrazine, fluphenazine, perazine, perphenazine, prochlorperazine, thiethylperazine, thiopropazate, thioproperazine and trifluoperazine, or salts thereof.
  5. 5. The use as claimed in any preceding claim wherein the medicament comprises from 0.1 to 100 mg of piperazine phenothiazine and/or the piperazine phenothiazine derivative.
  6. 6. The use as claimed in any preceding claim wherein the medicament is a transdermal, oral, buccal or sublingual medicament for the treatment of irritable bowel syndrome.
  7. 7. The use of piperazine phenothiazine or a derivative thereof, preferably prochlorperazine, or a salt thereof, for the treatment of irritable bowel syndrome.
  8. 8. A medicament for the treatment of irritable bowel syndrome, the medicament including a pharmaceutically effective amount of piperazine phenothiazine, a piperazine phenothiazine derivative or a salt thereof.
  9. 9. A medicament as claimed in claim 8 in the form of buccal or sublingual tablets, oral tablets, granules, capsules, transdermal patches, suppositories or injections.
  10. 10. A medicament as claimed in either one of claims 8 and 9 further comprising pharmaceutically acceptable ingredients selected from granulating agents, tableting agents, flavours, colours, carriers, diluents and/or excipients.
  11. 11. A medicament as claimed in any one of claims 9 and 10 wherein the buccal medicament comprises at least one monosaccharide or disaccharide and one or more gums.
  12. 12. A pack for the treatment of irritable bowel syndrome including: i) piperazine phenothiazine, a piperazine phenothiazine derivative or a salt thereof; and ii) instructions for the use thereof in the treatment of irritable bowel syndrome.
  13. 13. A pack as claimed in claim 12 wherein the piperazine phenothiazine, derivative thereof or a salt thereof is included in a medicament.
  14. 14. Use, medicament or pack according to the invention substantially as illustrated or described in any of the Examples.
GB0103328A 2001-02-12 2001-02-12 Compositions to treat irritable bowel syndrome Withdrawn GB2371983A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
GB0103328A GB2371983A (en) 2001-02-12 2001-02-12 Compositions to treat irritable bowel syndrome

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB0103328A GB2371983A (en) 2001-02-12 2001-02-12 Compositions to treat irritable bowel syndrome

Publications (2)

Publication Number Publication Date
GB0103328D0 GB0103328D0 (en) 2001-03-28
GB2371983A true GB2371983A (en) 2002-08-14

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Family Applications (1)

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Country Status (1)

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GB (1) GB2371983A (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2433887A (en) * 2006-01-04 2007-07-11 Reckitt Benckiser Healthcare Pack for phenothiazine derivatives
US9695138B1 (en) 2016-10-17 2017-07-04 Acenda Pharma, Inc. Phenothiazine derivatives and methods of use thereof

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001011077A2 (en) * 1999-08-11 2001-02-15 Cedars-Sinai Medical Center Methods of diagnosing or treating irritable bowel syndrome and other disorders

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001011077A2 (en) * 1999-08-11 2001-02-15 Cedars-Sinai Medical Center Methods of diagnosing or treating irritable bowel syndrome and other disorders

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Martindale: The Extra Pharmacopoeia (ed Reynolds et al) 1996pgs 730-732 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2433887A (en) * 2006-01-04 2007-07-11 Reckitt Benckiser Healthcare Pack for phenothiazine derivatives
US9695138B1 (en) 2016-10-17 2017-07-04 Acenda Pharma, Inc. Phenothiazine derivatives and methods of use thereof
US9850219B1 (en) 2016-10-17 2017-12-26 Acenda Pharma, Inc. Phenothiazine derivatives and methods of use thereof

Also Published As

Publication number Publication date
GB0103328D0 (en) 2001-03-28

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