WO1994005273A1 - Compositions gastro-intestinales contenant du dimethylsulfone et du dimethylsulfoxyde - Google Patents

Compositions gastro-intestinales contenant du dimethylsulfone et du dimethylsulfoxyde Download PDF

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Publication number
WO1994005273A1
WO1994005273A1 PCT/GB1993/001879 GB9301879W WO9405273A1 WO 1994005273 A1 WO1994005273 A1 WO 1994005273A1 GB 9301879 W GB9301879 W GB 9301879W WO 9405273 A1 WO9405273 A1 WO 9405273A1
Authority
WO
WIPO (PCT)
Prior art keywords
dimethylsulphoxide
composition
methylsulphonylmethane
treatment
formulation
Prior art date
Application number
PCT/GB1993/001879
Other languages
English (en)
Inventor
Aws Shakir Mustafa Salim
Original Assignee
Aws Shakir Mustafa Salim
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
Priority claimed from GB929218710A external-priority patent/GB9218710D0/en
Priority claimed from GB939310610A external-priority patent/GB9310610D0/en
Application filed by Aws Shakir Mustafa Salim filed Critical Aws Shakir Mustafa Salim
Priority to AU49750/93A priority Critical patent/AU4975093A/en
Publication of WO1994005273A1 publication Critical patent/WO1994005273A1/fr

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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
    • A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
    • A61K31/10—Sulfides; Sulfoxides; Sulfones

Definitions

  • the present invention relates to a synergistic composition for use in the treatment and improving the condition of the gastrointestinal tract, and in particular its mucosa.
  • the present invention offers a unique approach in the management of gastrointestinal diseases by offering synergistic pharmaceutical compositions which remove the mediators of gastrointestinal disease while sustaining the integrity of the mucosa against these diseases and stimulating the repair of any damage already sustained. Therefore, this invention provides protection against and treatment for a large spectrum of gastrointestinal diseases.
  • the present invention presents a synergistic pharmaceutical composition comprising methylsulphonylmethane with dimethylsulphoxide.
  • compositions of this invention has been surprisingly found to protect the mucosa of the oesophagus, stomach, duodenum and intestines against injury and damage besides enhancing the healing of its acute and chronic injury, inflammation and the various types of ulceration including the stress-induced variety.
  • this invention sustains the integrity of the oesphageal and gastrointestinal mucosa and protects against the recurrence of their non-mechanical injuries such as those caused by acid-peptic digestion, drugs, inflammatory processes be they specific or non-specific or ulceration whether stress-induced or otherwise.
  • compositions of this invention exhibit a synergistic action in that the sum total of the actions of the individual active ingredients is les ⁇ than that achieved by their combination together.
  • compositions of the invention exert the beneficial property of adhesion to the mucosa thereby affording prolonged contact with the treatment zone and an enhanced therapeutic delivery.
  • the present invention includes a vasodilator such as for example menthol in order to further increase the effectiveness of the composition of the invention in the mucosa.
  • a vasodilator such as for example menthol
  • this invention provides a composition of the invention in intimate admixture with a physiologically acceptable carrier or vehicle for use in the treatment of the oesophagus and gastrointestinal tract.
  • the carrier or vehicle should be acceptable in terms of exerting no deleterious actions on the gastrointestinal tract and being compatible with all the other ingredients of the invention. Suitable vehicles are well known in the art_being noted for example in such standard works as the British Pharmacopoeia and the British National Formulary.
  • oxygen-derived free radicals which are the cytotoxic agents involved in tissue damage and injury besides impairing the process of healing and repair.
  • cytoprotection which refers to sustaining the physio-chemical properties of living tissues, thus increasing their resistance to noxious stimuli.
  • compositions of the present invention can be administered orally, or parenterally, in particular by intravenous injection, or per rectum.
  • compositions of the invention and any accompanying material may be presented as a draught in water or in a syrup, in capsules, sachets, boluses or tablets, as an aqueous or oleaginous solution or suspension or in suspension in a syrup, such suspensions optionally including suspending agents or as an oil-in-water or water-in-oil emulsion.
  • the compositions of this invention may also be taken orally in an alcoholic drink be that a spirit, wine or beer.
  • the non-alcoholic forms of these drinks may also serve as vehicles for the oral consumption of the invention.
  • the present invention can be added for oral administration to any fruit juices, mineral waters be they carbonated or not, and to all forms of soft drinks.
  • flavouring, sweetening, preserving, thickening or emulsifying agents may be included in the formulation.
  • Tablets may contain the compositions of the invention and any accompanying material as a powder or granules optionally mixed with binders, lubricants, inert diluents or surface-active or dispersing agents.
  • compositions of the invention and any accompanying material may be presented in sterile solutions or suspensions in aqueous or oleaginous vehicles, which may also contain preservatives and material for rendering the solution or suspension isotonic with the blood of the intended recipient.
  • aqueous or oleaginous vehicles which may also contain preservatives and material for rendering the solution or suspension isotonic with the blood of the intended recipient.
  • Such formulations may conveniently be presented in unit-dose or multi-dose sealed containers.
  • Other suitable vehicles are well known in the art and are presented in all its standard publications.
  • the active ingredients of the invention are preferably presented in solution, suspension, or emulsion at a concentration of from 0.5 to 15% w/v more preferably 1 to 10% w/v e.g. 2% w/v in unit multidose form.
  • each unit dose preferably contains from 200 to 1000 mg of each of the ingredients.
  • This invention can also be directly delivered to the lung via smoke and in this respect, can be added as a powder or solution to tobacco leaves or to the tobacco of cigarettes, cigars and pipes.
  • the invention may also be included as a solution or powder in the cigarette's filter or small delivery compartments included in the cigarette. These compartments may contain the invention in the form of granules which evaporate upon contact with smoke, thus delivering their substances to be carried by the smoke.
  • dimethylsulphoxide and methylsulphonylmethane are administered at a dosage range of from 10 to 400 mg/kg body weight per day, preferably from 20 to 60 mg/kg body weight per day.
  • the dosage may be administered in one or more doses per day and is preferably given at intervals of from 2 to 8 hours, most preferably every 6 hours.
  • the ingredients of the compositions of this invention are administered in a slow release or sustained release vehicle, various suitable vehicles of this type being known in the art.
  • papaverine is included, this is generally used at a dosage of lmg/kg body weight per day.
  • Addition of procaine is most preferably at a dosage in the range from 30 to 50mg/kg body weight per day.
  • Menthol on the other hand, is usually added in a dosage range of from 20 to 40mg/kg body weight per day.
  • aqueous solutions were prepared with the following compositions:
  • compositions are prepared at a temperature of about 25°c.
  • the appropriate volume of the dimethylsulphoxide stock solution is measured then 10 grams of methylsulphonylmethane are added alone or if indicated with one gram of finely ground menthol crystals.
  • the solution is stirred for a few seconds.
  • the volume is then made up to 100ml with double distilled water and the whole mixture is stirred for a few seconds before being placed in airtight dark coloured glass bottles and stored at a temperature not exceeding 26°c.
  • This composition should not be used for at least 12 hours, should not be left exposed to the air for long periods and should not be directly exposed to sunlight.
  • Capsules for use in treating the oesophagus and gastrointestinal tract were prepared with the following compositions:
  • Capsules were prepared at a room temperature of 26°c. When making capsules which contain menthol, the crystals of this agent were first finely ground. The appropriate weight of powder of each ingredient is added and the whole preparation is thoroughly mixed then filled into gelatinous capsules. These capsules were stored in opague or dark coloured glass containers away from direct light and at room temperatures not exceeding 26°c.
  • each of MSM and DMSO exhibit cytoprotection against tissue injury and interact with each other in this respect synergistically.
  • the mechanism of this action is believed to be scavenging oxygen-derived free radicals which mediate tissue damage.
  • mice were similarly gavaged with 1ml of double distilled water or solutions of methylsulphonyl methane (MSM) and/or dimethylsulphoxide (DMSO) prepared in double distilled water.
  • MSM methylsulphonyl methane
  • DMSO dimethylsulphoxide
  • Example l.A 5ml every 6 hours
  • cimetidine 400mg b.d. After treatment for 4 weeks endoscopy was repeated.
  • Consecutive patients who were smokers and who had endoscopy proven duodenal ulceration occurring for the first time were randomized into one of 3 groups provided the ulceration was larger than 0.5cm in diameter but not of the giant variety, i.e. >2.5cm in diameter, and treated for 8 weeks then endoscoped again.
  • the study groups received the following treatments: (1) saline, 5ml every 6 hours, and placebo, 400mg b.d., (2) saline, 5ml every 6 hours and cimetidine, 400mg b.d., and (3) the composition listed under Example l.B, 5ml every 6 hours, and cimetidine, 400mg b.d.
  • Cimetidine was significantly more effective than placebo in stimulating the healing of peptic ulceration (25(71%) vs 11 (30%)), an action which was significantly (p ⁇ 0.01) heightened by the addition of the present invention where complete healing with an intact duodenal mucosa was observed in all the patients at the end of the study. D.
  • Example 1A The cumulative relapse rate in the control group during the maintenance therapy year was 63% (17 cases). While cimetidine significantly (p ⁇ 0.01) reduced this rate (31%, 8 cases), its efficacy was further increased (p ⁇ 0.01) by addition of the novel composition of Example l.A where the overall relapse rate decreased to 7% (2 cases) .
  • Treatment lasted for 5 days. Twenty patients were randomized to the control group (14 women and 6 men, age range 25 to 70 years, mean 57) and 22 patients were randomized to the active therapy group (17 women and 5 men, age range 23 to 69 years, mean 54) .
  • Remission or recovery from attacks indicates that the patient has become free of symptoms and has no diarrhoea; flexible sigmoidoscopy shows no contact bleeding or deeply congested mucosa discharging blood, mucus, or pus; haematological and biochemical data return to normal values; and histological examination shows the disease to be inactive. Patients were given a low residue and milk-free diet, which is high in protein and calories, until their attack had subsided.
  • DMSO dimethylsulphoxide
  • MSM methylsulphonylmethane

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention se rapporte à des compositions synergiques comprenant du méthylsulfonylméthane et du diméthylsulfoxyde, ainsi qu'à leur utilisation dans des formulations et des méthodes thérapeutiques et prophylactiques contre les lésions gastro-intestinales.
PCT/GB1993/001879 1992-09-04 1993-09-03 Compositions gastro-intestinales contenant du dimethylsulfone et du dimethylsulfoxyde WO1994005273A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU49750/93A AU4975093A (en) 1992-09-04 1993-09-03 Gastrointestinal compositions containing dimethylsulfone and dimethylsulfoxide

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB929218710A GB9218710D0 (en) 1992-09-04 1992-09-04 Gastrointestinal treatment
GB9218710.3 1992-09-04
GB939310610A GB9310610D0 (en) 1993-05-22 1993-05-22 Gastrointestinal treatment
GB9310610.2 1993-05-22

Publications (1)

Publication Number Publication Date
WO1994005273A1 true WO1994005273A1 (fr) 1994-03-17

Family

ID=26301540

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1993/001879 WO1994005273A1 (fr) 1992-09-04 1993-09-03 Compositions gastro-intestinales contenant du dimethylsulfone et du dimethylsulfoxyde

Country Status (2)

Country Link
AU (1) AU4975093A (fr)
WO (1) WO1994005273A1 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6299902B1 (en) 1999-05-19 2001-10-09 The University Of Georgia Research Foundation, Inc. Enhanced transdermal anesthesia of local anesthetic agents
WO2012104492A1 (fr) * 2011-02-03 2012-08-09 Stora Enso Oyj Procédé pour la production de diméthylsulfone par oxydation d'un milieu à base de méthanol obtenu à partir d'un procédé de traitement de cellulose au sulfate
EP2493314A1 (fr) * 2009-10-30 2012-09-05 Abela Pharmaceuticals, Inc. Préparations à base de diméthylsulfoxyde (dmso) et de méthylsulfonylméthane (msm) utilisées pour traiter l'arthrose
JP2013523769A (ja) * 2010-03-31 2013-06-17 アベラ ファーマスーティカルズ インコーポレイテッド 自閉症治療用ジメチルスルホキシド（ｄｍｓｏ）製剤
US9186297B2 (en) 2005-09-12 2015-11-17 Abela Pharmaceuticals, Inc. Materials for facilitating administration of dimethyl sulfoxide (DMSO) and related compounds
US9186472B2 (en) 2005-09-12 2015-11-17 Abela Pharmaceuticals, Inc. Devices for removal of dimethyl sulfoxide (DMSO) or related compounds or associated odors and methods of using same
US9427419B2 (en) 2005-09-12 2016-08-30 Abela Pharmaceuticals, Inc. Compositions comprising dimethyl sulfoxide (DMSO)
AU2015202432B2 (en) * 2009-10-30 2017-01-05 Abela Pharmaceuticals, Inc. Dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) formulations to treat osteoarthritis

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2057875A (en) * 1979-08-30 1981-04-08 Herschler R J Dimethyl sulphoxide compositions

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2057875A (en) * 1979-08-30 1981-04-08 Herschler R J Dimethyl sulphoxide compositions

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6299902B1 (en) 1999-05-19 2001-10-09 The University Of Georgia Research Foundation, Inc. Enhanced transdermal anesthesia of local anesthetic agents
US9186297B2 (en) 2005-09-12 2015-11-17 Abela Pharmaceuticals, Inc. Materials for facilitating administration of dimethyl sulfoxide (DMSO) and related compounds
US9427419B2 (en) 2005-09-12 2016-08-30 Abela Pharmaceuticals, Inc. Compositions comprising dimethyl sulfoxide (DMSO)
US9186472B2 (en) 2005-09-12 2015-11-17 Abela Pharmaceuticals, Inc. Devices for removal of dimethyl sulfoxide (DMSO) or related compounds or associated odors and methods of using same
JP2013509440A (ja) * 2009-10-30 2013-03-14 アベラ ファーマスーティカルズ インコーポレイテッド 変形性関節症を治療するためのジメチルスルホキシド（ｄｍｓｏ）およびメチルスルホニルメタン（ｍｓｍ）製剤
AU2010313253B2 (en) * 2009-10-30 2015-02-19 Abela Pharmaceuticals, Inc. Dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) formulations to treat osteoarthritis
EP2493314A4 (fr) * 2009-10-30 2013-05-01 Abela Pharmaceuticals Inc Préparations à base de diméthylsulfoxyde (dmso) et de méthylsulfonylméthane (msm) utilisées pour traiter l'arthrose
EP2493314A1 (fr) * 2009-10-30 2012-09-05 Abela Pharmaceuticals, Inc. Préparations à base de diméthylsulfoxyde (dmso) et de méthylsulfonylméthane (msm) utilisées pour traiter l'arthrose
AU2015202432B2 (en) * 2009-10-30 2017-01-05 Abela Pharmaceuticals, Inc. Dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) formulations to treat osteoarthritis
US9839609B2 (en) 2009-10-30 2017-12-12 Abela Pharmaceuticals, Inc. Dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) formulations to treat osteoarthritis
US9855212B2 (en) 2009-10-30 2018-01-02 Abela Pharmaceuticals, Inc. Dimethyl sulfoxide (DMSO) or DMSO and methylsulfonylmethane (MSM) formulations to treat infectious diseases
US10596109B2 (en) 2009-10-30 2020-03-24 Abela Pharmaceuticals, Inc. Dimethyl sulfoxide (DMSO) or DMSO and methylsulfonylmethane (MSM) formulations to treat infectious diseases
JP2013523769A (ja) * 2010-03-31 2013-06-17 アベラ ファーマスーティカルズ インコーポレイテッド 自閉症治療用ジメチルスルホキシド（ｄｍｓｏ）製剤
WO2012104492A1 (fr) * 2011-02-03 2012-08-09 Stora Enso Oyj Procédé pour la production de diméthylsulfone par oxydation d'un milieu à base de méthanol obtenu à partir d'un procédé de traitement de cellulose au sulfate

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Publication number Publication date
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