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
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
  • A61K9/2806—Coating materials
  • A61K9/2833—Organic macromolecular compounds
  • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
  • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• • 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
  • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
  • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
  • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
• • 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
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
  • A61K9/2806—Coating materials
  • A61K9/282—Organic compounds, e.g. fats

Definitions

• the present invention relates to oral compositions containing type A2 proanthocyanidins in gastroprotected form for the treatment of acute cystitis induced by fimbriated bacterial forms.
• Recurrent cystitis together with acute cystitis (also known as simple or uncomplicated cystitis), interstitial cystitis, bacterial prostatitis and pyelonephritis, belongs to the UTI (Urinary Tract Infection) group.
• UTI User Tract Infection
• Vaccinium macrocarpon derivatives effectively counteracts the symptoms, even in the absence of antibiotic treatment.
• the use of the derivative obviously applies to patients who have negative urine cultures but are expected to become positive again within 4-8 weeks.
• the monographs of the plant in question still cite the presence of molecules such as benzoic acid and fructose, the first of which is converted to hippuric acid, causing acidification of the urine with a consequent antibacterial effect, while the second performs a direct action on E. coli strains with type 1 filamentous structures which are consequently mannose- sensitive; however, these two substances are unlikely to explain the action of the preparation in the urological field (Pappas E, Schaich KM Crit Rev Food Sci Nutr. 2009 Oct;49(9):741-781).
• Vaccinium macrocarpon extract is characterised by type A proanthocyanidins (PAC), and their presence and characterisation, in terms of the dose administered, has been strongly correlated with the claimed activity against recurrent cystitis (Howell AB, Botto H, Combescure C, Blanc-Potard AB, Gausa L et al. BMC Infect Dis. 2010, 14; 10-94).
• PAC proanthocyanidins
• Acute cystitis in this context means all non-recurrent forms of cystitis, including interstitial cystitis, pyelonephritis and bacterial prostatitis when induced by fimbriated bacterial forms.
• PACs are polyphenolic structures with strongly antioxidant properties. Like all antioxidants they are rather unstable, and industrial and formulation management which fails to take account of this characteristic tends to reduce their content (Pappas E, Schaich KM Crit Rev Food Sci Nutr. 2009 Oct; 49(9):741-781). PACs are also substances able to interact with bacteria which are typical gastric colonisers, like H. pilori (Matsushima M, Suzuki T, Masui A, Kasai K, Kouchi T et al J Gastroenterol Hepatol. 2008 Dec; 23(Suppl 2) S 175-S 180). The presence of the latter in a patient's stomach obviously reduces the quantity of PAC available to counteract the action of E. coli.
• proanthocyanidin A2 forms complexes, via proline residues, with the proteins of the salivary mucosa and the oesophageal, gastric and intestinal fluids.
• the increased molecular weight of the proanthocyanidin A2-protein limits the possibility of molecular motion of the PACs along the enterocyte line. In this form, the PACs are less active and their bioavailability is lower, which reduces their presence in the urine.
• the invention therefore relates to pharmaceutical forms of PAC such as tablets, powders, granulates and capsules coated with natural or synthetic film-forming substances permitted for dietary use (e.g. shellac) and non-dietary use (hydroxypropyl methylcellulose).
• PAC pharmaceutical forms of PAC such as tablets, powders, granulates and capsules coated with natural or synthetic film-forming substances permitted for dietary use (e.g. shellac) and non-dietary use (hydroxypropyl methylcellulose).
• compositions will contain at least 18 mg of PAC assayed by the DMAC analysis method (Ocean Spray, Maryland, USA) or 54 mg assayed by a method validated according to the European Pharmacopoeia.
• the gastroprotected product allows patients to be treated during the acute stage of cystitis. In this case, the positive urine culture becomes negative. It has been found that if the gastroprotected product is administered at the acute cystitis stage by recruiting patients who have no fever, with symptoms (dysuria, nocturia, urinary urgency, etc.) which are not severe, but with a positive urine culture (> 100,000 CFU/mL), the symptoms disappear and the urine culture becomes negative.
• the patients were divided into 3 treatment groups: 600 mg/day in the evening, 600 mg every 12 hours and 1200 mg/day in the evening.
• the treatment lasted for 5 days in all cases.
• Tables 1-3 show the bioburden and tolerability trends in each patient.
• the formulations according to the invention are clearly clinically effective in the treatment of acute cystitis.
• formulations according to the invention are set out below.
• the quantities are expressed as mg/tablet.
• Vaccinium macrocarpon (30% Eur. Ph.) 200,000

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• Health & Medical Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• Life Sciences & Earth Sciences (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Medicinal Preparation (AREA)
• Preparation Of Compounds By Using Micro-Organisms (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Micro-Organisms Or Cultivation Processes Thereof (AREA)

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• 2011
  • 2011-03-15 IT IT000409A patent/ITMI20110409A1/it unknown
• 2012
  • 2012-03-14 WO PCT/EP2012/054453 patent/WO2012123491A1/en active Application Filing
  • 2012-03-14 EP EP12717059.5A patent/EP2685967A1/de not_active Withdrawn

Non-Patent Citations (3)

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