Classifications

• • 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
  • A61K9/0065—Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus

Definitions

• This invention relates to pharmaceutical products and in particular to compositions for the treatment of reflux oesophagitis, gastritis or peptic ulceration.
• Reflux oesophagitis occurs when small amounts of gastric juice, food and/or bile acids pass into the lower part of the oesophagus and cause oesophageal inflammation accompanied by pain which may manifest itself in the form of heartburn.
• One approach to the problem of reflux oesophagitis comprises the administration of a preparation which on contact with gastric acid generates a carbonated gelatinous foam or raft which floats on the stomach contents. When reflux occurs it is this raft which precedes the stomach contents into the oesophagus thus protecting the mucosa from further irritation.
• a pharmaceutical product for the treatment of reflux oesophagitis, gastritis or peptic ulceration in the form of a chewable soft gelatin capsule with a fill comprising (a) polymeric material selected from alginic acid, alginates, pectin, xanthan, gellan, carageenan and mixtures thereof; (b) a carbonate or bicarbonate salt; (c) an oil-based or hydrophilic based liquid vehicle; wherein on oral ingestion the gelatin capsule shell ruptures and the fill reacts with the acid contents of the stomach thereby producing a carbonated floating gelatinous raft of such rigidity that in the penetration test as hereinafter defined there is not complete penetration.
• the polymeric material is the sodium, potassium, ammonium, magnesium or calcium salt of alginic acid or the propylene glycol esters or mixtures thereof.
• rafts of improved strength are obtained if the composition includes a source of divalent calcium or trivalent aluminium ion which act as cross-linking agents.
• Suitable sources of calcium ions are those derived from the carbonate, lactate, chloride, gluconate, phosphate, hydrogen phosphate, sulphate, tartrate or citrate salts.
• Suitable sources of aluminium ions are those derived from the carbonate, lactate, glycinate or phosphate salts or from aluminium magnesium carbonate hydroxide, agaldrate, aluminium sodium carbonate hydroxide or aluminium sodium silicate. Conveniently the relative quantities by weight of the calcium salt or aluminium compound to the alginic acid or alginate calculated as ions are 4 to 120 Ca 2+ to 500 alginate " or 2 to 80 Al 3+ to 500 alginate" respectively.
• Suitable carbonate or bicarbonate salts are potassium carbonate or bicarbonate, sodium carbonate or bicarbonate, calcium carbonate, sodium glycine carbonate, magnesium carbonate or aluminium carbonate.
• the carbonate or bicarbonate salt is present in an amount so as to provide an adequate volume of gas (carbon dioxide) to float the gel produced when the polymeric material contacts the gastric acid in the stomach.
• gas carbon dioxide
• the relative quantities by weight of polymeric material to the carbonate or bicarbonate calculated as ions is 35 to 300 CO 3 2 " or HC0 3 ⁇ to 500 polymeric material.
• the rigidity and thickness of the carbonated raft formed on contact with the gastric acid will depend upon the ratio of carbonate or bicarbonate to the polymeric material and upon the grade of the polymeric material.
• Suitable oil-based liquid vehicles are natural oils such as soya bean oil, fractionated coconut oil, mineral oils, triacetin, ethyl oleate, hydrogenated natural oil and mixtures thereof.
• Suitable hydrophilic based liquid vehicles are polyethylene glycols (PEG's) particularly PEG 400 and PEG 600, glycofurol, polyglycerols, propylene glycol, Transcutol, polysorbate and propylene carbonate and mixtures thereof.
• the invention also includes a method of treating reflux oesophagitis, gastritis or peptic ulceration which comprises administration of an effective amount of a product which is capable of forming a floating gelatinous raft when contacted with the acid contents of the stomach said raft being of such rigidity that in the penetration test as hereinafter defined there is not complete penetration and said product being in the form of a chewable soft gelatin capsule with a fill comprising (a) polymeric material selected from alginic acid, alginates, pectin, xanthan, gellan, carageenan and mixtures thereof; (b) a carbonate or bicarbonate salt; (c) an oil-based or hydrophilic based liquid vehicle.
• a fill comprising (a) polymeric material selected from alginic acid, alginates, pectin, xanthan, gellan, carageenan and mixtures thereof; (b) a carbonate or bicarbonate salt; (c) an oil-based or hydrophilic based liquid vehicle.
• the gelatin capsules may be simultaneously formed and filled using conventional methods and apparatus such as disclosed, for example, in an article by H. Seager in Pharmaceutical Technology September 1985.
• All the ingredients of the fill material including the liquid vehicle are mixed together, with heating if necessary, until the desired consistency for filling and the desired unifor ity is obtained.
• the encapsulation machine is suitably an R P Scherer encapsulation machine.
• a surfactant may be included in the fill.
• the polymeric materials will have a thickening effect upon the liquid fill.
• This thickening effect may be further increased if so desired by the inclusion of a thickening agent such as hydrogenated vegetable oils, glyceryl monostearate, glyceryl monopalmitate, beeswax (or other high melting point fat or wax) or a dispersed thickener such as colloidal silicon dioxide.
• a suitable thickening agent may be one or more high molecular weight PEG's.”
• the capsules will be suitably shaped and sized so as to be readily ingestible by a person following chewing.
• Example 1 The invention is illustrated by the following Examples: Example 1
• Capsules in a standard gelatin shell were prepared having the following fill:
• Capsules were prepared as in Example 1 except that the amount of calcium carbonate in the fill materials was increased to 100 mg.
• Example 3
• Capsules were prepared as in Example 1 having the following fill: Quantity/Capsule
• Example 4 were prepared as in Example 1 having the following fill:
• Example 5 1500 mg Example 5 Capsules were prepared as in Example 1 having the following fill:
• Capsules were prepared as in Example l having the following fill:
• the appropriate amount of product (equivalent to 6 doses of lg of polymeric material) was weighed and added to a 250ml tall-form beaker (height 120mm & diameter 60mm) previously weighed. A volume of 120ml of deionised water was added and the mixture homogenized for 5 minutes using the Silverson Model L4R ho ogenizer with a Turbular Unit 1" in diameter and a square hole high shear screen. The speed of the homogenizer was set at speed 4 / 5000-5200 rpm. In the case of Liquid Gaviscon and Algicon Mint, 120ml of the product was taken and added to a 250ml tall-form beaker.

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• Health & Medical Sciences (AREA)
• Nutrition Science (AREA)
• Physiology (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)
• Medicinal Preparation (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

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Publications (1)

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Cited By (9)

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Citations (3)

• 1994
  • 1994-10-28 AU AU80004/94A patent/AU8000494A/en not_active Abandoned
  • 1994-10-28 WO PCT/GB1994/002380 patent/WO1995011668A1/en not_active Application Discontinuation
  • 1994-10-28 JP JP7512497A patent/JPH09504286A/ja active Pending
  • 1994-10-28 BR BR9407916A patent/BR9407916A/pt not_active Application Discontinuation
  • 1994-10-28 EP EP94931124A patent/EP0725626A1/en not_active Withdrawn
  • 1994-10-28 NZ NZ27490194A patent/NZ274901A/en unknown
  • 1994-10-28 CN CN 94193934 patent/CN1133558A/zh active Pending
  • 1994-10-28 CA CA 2174777 patent/CA2174777A1/en not_active Abandoned
• 1996
  • 1996-04-24 NO NO961638A patent/NO961638L/no unknown

Patent Citations (3)

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