WO2003000299A1 - Preparation de laxatif - Google Patents

Preparation de laxatif Download PDF

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Publication number
WO2003000299A1
WO2003000299A1 PCT/AU2002/000819 AU0200819W WO03000299A1 WO 2003000299 A1 WO2003000299 A1 WO 2003000299A1 AU 0200819 W AU0200819 W AU 0200819W WO 03000299 A1 WO03000299 A1 WO 03000299A1
Authority
WO
WIPO (PCT)
Prior art keywords
magnesium sulphate
preparation
laxative
patient
capsules
Prior art date
Application number
PCT/AU2002/000819
Other languages
English (en)
Other versions
WO2003000299B1 (fr
Inventor
Michael David Levitt
Original Assignee
Colocaps Pty 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 Colocaps Pty Ltd filed Critical Colocaps Pty Ltd
Priority to AU2002312652A priority Critical patent/AU2002312652B2/en
Priority to NZ529895A priority patent/NZ529895A/en
Publication of WO2003000299A1 publication Critical patent/WO2003000299A1/fr
Publication of WO2003000299B1 publication Critical patent/WO2003000299B1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/10—Laxatives
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4816—Wall or shell material
    • A61K9/4825—Proteins, e.g. gelatin

Definitions

  • the present invention relates to a laxative preparation.
  • the laxative preparation of the present invention is particularly suited to oral administration for treatment of occasional and intractable constipation, and as an agent for complete bowel preparation prior to colonoscopy, barium enema x-ray examination and intestinal surgery.
  • Fibre supplements are popular because of their "healthy” image, because they are generally mild and because they are not habit forming. Their main disadvantages are that they are generally mild and that they result in considerable gas formation. Ironically, for people with moderate-severe constipation, fibre supplements rarely overcome the problem and often compound symptoms like abdominal pain and bloating as gas becomes "trapped" in the large intestine.
  • a further group of laxatives are the osmotic agents. These are typically concentrated salts or sugars and act to attract intracellular and intravascular water into the intestine. The column of water that this creates then distends the intestine and stimulates a genuinely natural contractile response from the intestinal smooth muscle.
  • Sugars include lactulose (Duphulac, Actilax), sorbitol (Sorbilax, diabetic sweets) and mannitol (also used in diabetic sweets). These tend to be relatively mild but are unpopular because of the substantial volumes of gas associated with their use and because they are of only mild-moderate activity.
  • Salts include Epsom salts (magnesium sulphate heptahydrate), sodium sulphate, magnesium oxide, sodium picosulphate and others. These are typically administered as an aqueous solution.
  • Epsom salts magnesium sulphate heptahydrate
  • sodium sulphate magnesium oxide
  • sodium picosulphate sodium picosulphate
  • the salts are much more potent than the sugars but are almost universally despised by patients because of their offensive taste - many people cannot tolerate them at all. Further, significant quantities of the salts must be ingested for the laxative effect. On the other hand, salts are effective, non-habit forming and (relatively) gasless.
  • dehydrated magnesium sulphate refers to solid magnesium sulphate with fewer waters of hydration that the heptahydrate MgS ⁇ 4 .7H 2 0, and/or a mixture of such magnesium sulphates that may include but does not exclusively comprise the heptahydrate. Disclosure of the Invention
  • a laxative preparation comprising dehydrated magnesium sulphate.
  • magnesium sulphate is a substantially more potent laxative than the conventionally administered aqueous solutions of magnesium sulphate heptahydrate.
  • the dehydrated magnesium sulphate is substantially provided in the form of anhydrous magnesium sulphate, magnesium sulphate monohydrate, magnesium sulphate dihydrate, magnesium sulphate trihydrate, magnesium sulphate tetrahydrate and/or a mixture thereof.
  • the dehydrated magnesium sulphate is substantially provided in the form of magnesium sulphate monohydrate.
  • the dehydrated magnesium sulphate is coated.
  • the dehydrated magnesium sulphate is coated to substantially inhibit rehydration by absorption of atmospheric water, and to negate the unpalatable bitter taste associated with the magnesium sulphate, thereby significantly improving palatability.
  • the present invention provides a more effective laxative than the existing salt type laxatives, with the substantial advantage of superior palatability.
  • the laxative preparation comprises a plurality of discrete units containing dehydrated magnesium sulphate, such as capsules, cachets, or tablets.
  • each discrete unit contains a predetermined amount of dehydrated magnesium sulphate.
  • each tablet of dehydrated magnesium sulphate may be coated to substantially inhibit absorption of atmospheric water.
  • the coating is provided in the form of the cachet, the dehydrated magnesium sulphate being contained therein.
  • the coating is provided in the form of the capsule, the dehydrated magnesium sulphate being contained therein.
  • the capsules may be provided in the form of standard pharmaceutical capsules, such as those formed from gelatine or cellulose.
  • the capsules are provided in the form of soft gelatine capsules.
  • a method for the treatment of a patient suffering from constipation including occasional and intractable constipation, the method including the step of administration of dehydrated magnesium sulphate to the patient.
  • a method for preparation of the bowel of a patient, prior to colonoscopy, barium enema x-ray examination, intestinal surgery or the like including the step of administration of dehydrated magnesium sulphate to the patient.
  • the present invention further provides a method for the preparation of a medicament for the treatment of a patient suffering from constipation, including occasional and intractable constipation, using dehydrated magnesium sulphate.
  • the present invention further provides a method for the preparation of a medicament for the preparation of the bowel of a patient, prior to colonoscopy, barium enema x-ray examination, intestinal surgery or the like, using dehydrated magnesium sulphate.
  • the patient is mammalian. In a highly preferred form of the invention, the patient is human. Best Mode(s) for Carrying Out the Invention
  • Dehydrated magnesium sulphate is prepared by heating magnesium sulphate heptahydrate in the presence of a hygroscopic agent, then allowing such to cool in the presence of dry air. The temperature to which the hydrate is heated determines the degree of dehydration. At a temperature of approximately 120°C, six waters of crystallisation will be removed, leaving the monohydrate. Removal of the last waters of crystallisation requires temperatures of approximately 250°C. Accordingly, it is anticipated that balancing the energy required to remove the last water of crystallisation against the increase in the efficacy of the laxative will mean the monohydrate is the best compromise.
  • the dehydrated magnesium sulphate (substantially monohydrate) may then be introduced into soft gelatine type pharmaceutical capsules, , for consumption by a patient. Given the quantity of the preparation required for the laxative effect, larger capsules are preferred.
  • a quantity of magnesium sulphate of unknown hydration was obtained from a commercial supplier.
  • magnesium sulphate heptahydrate portions of magnesium sulphate heptahydrate were placed in capsules and administered to two subjects that had previously been unable to ingest a solution of magnesium sulphate. The patients had no difficulty ingesting the capsules.
  • magnesium sulphate tetrahydrate was placed in each of a quantity of capsules, which were administered to three subjects. Effective bowel cleansing was achieved with from 60 - 80 capsules taken 10 at a time on the hour. Even allowing for the need to take 100 capsules (10 capsules every 30 minutes would be acceptable), this represents a total of only 32gm - clearly more potent than other agents in current use. It is anticipated that the monohydrate would be more potent still.
  • a quantity of commercially available Epsom salts and a quantity of commercially available dehydrated magnesium sulphate, predominantly tetrahydrate were placed in capsules.
  • a comparative trial of the efficacy of the capsules was conducted in 20 patients undergoing a large bowel resection for a variety of pathological conditions. Patents were not aware of whether they had received Epsom salts or the dehydrated magnesium sulphate.
  • the group that received the Epsom salt capsules comprised 4 men and 6 women, ranging in age from 13 to 87 years (median 68.5 years).
  • the group that received the dehydrated magnesium sulphate comprised 6 men and 4 women, ranging in age from 27 to 73 (median 54 years).
  • Each group was issued with identical dietary instructions and 150 capsules, and each group member was instructed to take 10 capsules on an hourly basis until their bowel actions were 'liquid and clear'.
  • the number of capsules required by the group that received Epsom salts varied between 80 and 120, with a median of 100.
  • the number of capsules required by the group that received dehydrated magnesium sulphate varied between 60 and 100, with a median of 70. Accordingly, a significantly lower number of capsules were required by the patients receiving the dehydrated magnesium sulphate.
  • each patient was administered a standard 'Fleet' enema and the nurse (also unaware of the group to which the patient belonged) was asked to grade the nature of the enema effluent on a scale of 1 to 4, where 1 represented heavy faecal contamination, 2 represented moderate faecal contamination, 3 represented residual faecal particles and 4 represented clear effluent.
  • the ratings for the Epsom salts group varied between 1 and 4, with a median of 2.5, corresponding to between moderate faecal contamination and residual faecal particles.
  • the ratings for the dehydrated magnesium sulphate group varied between 2 and 4, with a median of 3.3, corresponding to between residual faecal particles and clear effluent.
  • the dehydrated magnesium sulphate of the present invention is substantially more effective than Epsom salts, and when coated, such as when provided in capsules, has the advantage of overcoming the extreme unpalatability of magnesium sulphate salts. Modifications and variations such as would be apparent to the skilled addressee are considered to fall within the scope of the present invention.

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  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Inorganic Chemistry (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne une préparation de laxatif à base de sulfate de magnésium déshydraté.
PCT/AU2002/000819 2001-06-25 2002-06-21 Preparation de laxatif WO2003000299A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU2002312652A AU2002312652B2 (en) 2001-06-25 2002-06-21 Laxative preparation
NZ529895A NZ529895A (en) 2001-06-25 2002-06-21 Laxative preparation

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AUPR5907 2001-06-25
AUPR5907A AUPR590701A0 (en) 2001-06-25 2001-06-25 Laxative preparation

Publications (2)

Publication Number Publication Date
WO2003000299A1 true WO2003000299A1 (fr) 2003-01-03
WO2003000299B1 WO2003000299B1 (fr) 2003-05-22

Family

ID=3829876

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/AU2002/000819 WO2003000299A1 (fr) 2001-06-25 2002-06-21 Preparation de laxatif

Country Status (3)

Country Link
AU (1) AUPR590701A0 (fr)
NZ (1) NZ529895A (fr)
WO (1) WO2003000299A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008138085A2 (fr) * 2007-05-10 2008-11-20 Fermavi Eletroquímica Ltda Procédé servant à encapsuler des substances chimiquement actives et produit encapsulé
US9919007B2 (en) 2013-03-15 2018-03-20 Braintree Laboratories, Inc. Dual use oral pharmaceutical composition tablets of sulfate salts and methods of use thereof

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3297413A (en) * 1964-03-20 1967-01-10 Dow Chemical Co Method of preparing mgso4 3h2o crystals

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3297413A (en) * 1964-03-20 1967-01-10 Dow Chemical Co Method of preparing mgso4 3h2o crystals

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
"The Merck Index", vol. 5513, 1983, MERCK & CO., INC., RAHWAY, NJ, USA, pages: 812 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008138085A2 (fr) * 2007-05-10 2008-11-20 Fermavi Eletroquímica Ltda Procédé servant à encapsuler des substances chimiquement actives et produit encapsulé
WO2008138085A3 (fr) * 2007-05-10 2009-03-12 Fermavi Eletroquimica Ltda Procédé servant à encapsuler des substances chimiquement actives et produit encapsulé
US9919007B2 (en) 2013-03-15 2018-03-20 Braintree Laboratories, Inc. Dual use oral pharmaceutical composition tablets of sulfate salts and methods of use thereof

Also Published As

Publication number Publication date
AUPR590701A0 (en) 2001-07-19
NZ529895A (en) 2005-02-25
WO2003000299B1 (fr) 2003-05-22

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