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
  • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
  • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
  • A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
  • A61K9/1676—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface having a drug-free core with discrete complete coating layer containing drug
• • 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
  • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
  • A61K31/47—Quinolines; Isoquinolines
  • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
• • 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
  • A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/04—Centrally acting analgesics, e.g. opioids

Definitions

• Opioids are drugs indispensable for the control of severe painful syndromes, but they cause many side effects that, sometimes, render their use by the patients impossible.
• Valkenberg (Valkenberg H., Epidemiologic considerations of the geriatric population. Gerontology 1988; 34, suppl. 1, 2 - 10) refers that 33% of the population of more than 55 years old suffers from rheumatic pains.
• pain is present in many other situations like, for example, in the operating and postoperative phase, in AIDS-affected people, etc.
• opioids are drugs that cause an intense analgesic reaction acting on specific receptors.
• opioid antagonists Drugs acting on the same receptors without causing any biological effect are defined as opioid antagonists.
• opioids for example, morphine, codeine and fentanyl can be cited. 5
• opioid antagonists naloxone, naltrexone and cholecystokinin can be mentioned.
• the treatment with opioids causes many and severe side effects such as sleepiness, nausea, emesis, constipation, confusion, pruritus, headache, ritention of urine, dysphoric reactions, respiratory depression and myoclonus.
• patent USP 5580876 A describes the use of morphine combined with the administration of low doses of naltrexone in mouse.
• Patent application PCT - WO 96/02251 describes the simultaneous intake of morphine and of an opioid antagonist in a ratio antagonist - morphine of 1,0 mg of antagonist per 1 mg of morphine.
• the ratio antagonist - morphine is fixed while in the clinical practice variable ratios are required in function of the individual reactions of the various patients. Furthermore the aim of said application is restricted to the prevention of addiction.
• naltrexone administration ranges between 0,01 and 0,9 mg per mg of morphine. Naltrexone is administered by mouth.
• This invention refers to the use of naltrexone in the preparation of pharmaceutical compositions to be administered by mouth suitable to prevent and control the side effects caused by the opioid therapy.
• the invention furthermore, refers to a therapeutic method to prevent and control the side effects caused by the treatment with opioids consisting in the administration by mouth of said compositions in quantity equal to 0,01 - 0,9 mg of naltrexone per mg of morphine.
• the main object of the present invention is to propose a fast, reliable and economic method for the production of tiles with irregular edges having a handcrafted look, starting from plates, consisting of tiles or natural or synthetic slabs.
• Another object is to propose a method allowing to produce tiles having at least a rectilinear regular edge fit for the joining with other coverings or for carrying out the end portions of covering and having irregular remaining edges.
• naltrexone for which the clinical experience has demonstrated a great reliability of use also for long periods of administration. Moreover naltrexone has the advantage that it can be administered by mouth.
• naltrexone is prepared in form of a multiparticulate pharmaceutical composition constituted by pellets of saccharose and starch coated with a polyvinylpyrrolidone and naltrexone layer.
• said composition has a potency of naltrexone ranging from 0,005 to 0,1 mg per mg.
• composition is prepared in form of hard gelatine capsules having a content of naltrexone ranging from 0,25 to 0,5 mg per single capsule.
• composition containing naltrexone is administered half an hour before morphine.
• the treatment with naltrexone was carried out by administering 0,5 mg by mouth half an hour before the administration of morphine.
• the treatment with mo ⁇ hine was carried out by administering 10 mg intramuscularly every 12 hours.
• the side effect incidence and the analgesic efficacy were evaluated by means of internationally accepted and validated questionnaires, utilized to evaluate the variation degrees of the single symptoms. After the first administration of naltrexone, a 60% reduction of the nausea subjective sensation and a 50% reduction of the emesis episodes was noted, while no variation of the analgesic efficacy of the morphine therapy was noted.
• Naltrexone was administered by mouth half an hour before the administration of mo ⁇ hine, in the dose of 0,25 mg every 12 hours.
• naltrexone a dose of 0,5 mg of naltrexone was administered every 12 hours, by mouth, half an hour before the administration of mo ⁇ hine. A 50% reduction of said side effects was observed, except for constipation.
• Example 1 Some examples of multiparticulate preparations are described, suitable for the administration of microdosages of naltrexone.
• the fluidization of the pellets was realized by means of an airflow having a temperature of 40° C. On the fluidized pellets the following solution was sprayed:
• pellets were analyzed as for the naltrexone HCl content, which came out to be 0,01 mg / mg. Moreover, the pellets were tested to check the dissolution pattern in water, utilizing the apparatus described in the European Pharmacopoeia - Par. 2.9.3. - Dissolution test for solid dosage forms - "Paddle Apparatus". The value observed was 100%) after 10 minutes.
• pellets obtained according to this example were encapsulated in hard gelatine capsules.
• Example 3 A preparation according to the technique of example 1 was carried out, using the following solution:
• microtablets were dosed in hard gelatine capsules to obtain the dosages of 2,5 and 1,25 mg of naltrexone HCl / capsule.
• the remaining part of granulate of example 5 was extruded by means of an extruder FUJI PAUDAL DG-L1 having a perforated disc of 0,8 mm and spheronized by means of a spheronizer FUJI PAUDAL Q-230T.
• the so obtained pellets were desiccated in desiccator at a temperature of 50°C, thus obtaining results similar to those of example 1.

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• Health & Medical Sciences (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Epidemiology (AREA)
• Emergency Medicine (AREA)
• Pain & Pain Management (AREA)
• Biomedical Technology (AREA)
• Neurology (AREA)
• Neurosurgery (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Organic Chemistry (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Compositions Of Oxide Ceramics (AREA)
• Electrotherapy Devices (AREA)
• Medicinal Preparation (AREA)

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• 2001
  • 2001-05-02 IT IT2001MI000907A patent/ITMI20010907A1/it unknown
• 2002
  • 2002-05-02 WO PCT/IB2002/001473 patent/WO2002087582A1/en not_active Application Discontinuation
  • 2002-05-02 RU RU2003135201/15A patent/RU2003135201A/ru not_active Application Discontinuation
  • 2002-05-02 EP EP02726358A patent/EP1395260A1/en not_active Withdrawn
• 2003
  • 2003-12-01 ZA ZA200309333A patent/ZA200309333B/en unknown

Non-Patent Citations (1)

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