WO2012123491A1 - Use of type a2 proanthocyanidins in gastroprotected form for the treatment of acute cystitis induced by fimbriated bacterial forms e - Google Patents

Use of type a2 proanthocyanidins in gastroprotected form for the treatment of acute cystitis induced by fimbriated bacterial forms e Download PDF

Info

Publication number
WO2012123491A1
WO2012123491A1 PCT/EP2012/054453 EP2012054453W WO2012123491A1 WO 2012123491 A1 WO2012123491 A1 WO 2012123491A1 EP 2012054453 W EP2012054453 W EP 2012054453W WO 2012123491 A1 WO2012123491 A1 WO 2012123491A1
Authority
WO
WIPO (PCT)
Prior art keywords
coli
proanthocyanidins
sterile
type
treatment
Prior art date
Application number
PCT/EP2012/054453
Other languages
French (fr)
Inventor
Francesco Di Pierro
Original Assignee
Velleja Research S.R.L.
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 Velleja Research S.R.L. filed Critical Velleja Research S.R.L.
Priority to EP12717059.5A priority Critical patent/EP2685967A1/en
Publication of WO2012123491A1 publication Critical patent/WO2012123491A1/en

Links

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

Landscapes

  • 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)
  • 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)

Abstract

Disclosed are oral compositions containing Type A2 proanthocyanidins in gastroprotected form for the treatment of acute cystitis induced by fimbriated bacterial forms.

Description

USE OF TYPE A2 PRQANTHQCYANIDINS IN GASTRQPRQTECTED FORM FOR THE TREATMENT OF ACUTE CYSTITIS INDUCED BY FIMBRIATED BACTERIAL FORMS E
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.
Prior art
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. These disorders are caused by uropathogenic strains of E. coli, very often of intestinal origin, which are able to proliferate until they exceed the threshold of 100,000 bacteria per ml of urine, the fundamental parameter for a correct diagnosis of cystitis. Like all disorders caused by bacterial infection, they require antibiotic treatment.
However, as reported by many authors, when the disorder recurs frequently (recurrent cystitis), the use of 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. This phenomenon (which differs from relapses, where the microbe that expands is obviously a residual bacterial clone that was not eliminated by the antibiotic treatment) is called "recurrence", and in the vast majority of cases appears to be caused by bacterial migration, associated with the anatomical proximity between the intestine and the urinary bladder, which allows some fimbriated strains to cross the septa forming the boundary between the two organs (Rossi R, Porta S, Canovi B. J Clin Gastroenterol. 2010 Sep;44, Suppl 1 ; S61-S62).
The use of cranberry juice obtained by crushing Vaccinium macrocarpon (Ericacea) to treat recurrent cystitis has been known since 1923 (Blatherwick J 1923 J Biol Chem 57: 815-818). Nowadays, the juice is rarely if ever used "as is", due to the unpalatability of the product. Instead, extracts with a type A proanthocyanidin (PAC) content of 0.5 to 80% have been obtained and used, first by producing products obtained by dehydrating the juice, and subsequently by normal extraction procedures. 30% preparations are now the most widely used, mainly due to their value for money.
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). Conversely, 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). By interacting directly with the type P fimbriated structures present on the uropathogenic strains of E. coli, these PACs, appear to prevent between the fimbriae from attaching to the receptor glycoprotein on the epithelium of the urinary bladder. This impediment seems to limit the adherence, and consequently the proliferative capacity, of E. coli, which is no longer capable of effective colonisation and causing disease (Pinzon-Arango PA, Liu Y, Camesano TA. J Med Food. 2009 Apr; 12(2):259-70). Description of the invention
It has now been discovered that gastroprotection of a formulation containing Vaccinium macrocarpon extract optimises its pharmacoclinical yield and makes its use in acute (non-recurrent) cystitis possible.
"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. Finally, 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.
These problems are solved by formulating the PACs as gastroprotected tablets. Gastroprotection prevents the disintegration of the active constituents in the stomach, and only allows their release at a pH of approx. 6.0-6.8, a value typical of the duodenum.
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).
The 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.
Administration of 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.
Clinical trial
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. Urine cultures were performed on recruitment, after 5 days' treatment and after a further 5-day wash-out (t=10).
Tables 1-3 show the bioburden and tolerability trends in each patient.
Table 1 Trend (CFU/mL) in patients with a diagnosis of acute cystitis treated for 5 days with 600 mg of gastroprotected preparation
Pat S t=0 t=5 t=10 T
FM F Enterococcus E. coli E. coli G
> 100,000 < 50.000 < 50.000
GD F E. coli E. coli Sterile E
> 100.000 < 50.000
GB F Proteus E. coli E. coli E
> 100.000 < 50.000 < 50.000
LP F Klebsiella Enterococcus E. coli E
> 100.000 > 100.000 < 50.000
FP M E. coli Sterile Sterile E
> 100.000
PS F Candida E. coli Sterile E
> 100.000 > 100.000
GS M Enterococcus Enterococcus E. coli E
> 100,000 < 50,000 < 50.000
Pat = patient; S = sex; T = tolerability; G = good; E = excellent
Table 2 Trend (CFU/mL) in patients with a diagnosis of acute cystitis treated for 5 days with 600 mg of gastroprotected preparation every 12 hours
Pat S t=0 t=5 t=10 T
VF M E. coli Sterile Sterile E
> 100.000
DW F Klebsiella E. coli Sterile E
> 100.000 > 100.000
RP F Enterococcus E. coli E. coli G
> 100,000 > 100,000 > 100,000
GS F Candida E. coli Sterile E
> 100,000 > 100,000
RP M Proteus E. coli Sterile E
> 100.000 < 50.000
PG M Candida Candida E. coli G
> 100.000 < 50.000 < 50.000
RP F E. coli E. coli Sterile E
> 100.000 < 50.000
LG F Enterococcus Sterile Sterile E
> 100,000
Pat = patient; S = sex; T = tolerability; G = good; E = excellent Table 3 Trend (CFU/mL) in patients with a diagnosis of acute cystitis treated for 5 days with 1200 mg of gastroprotected preparation
Pat S t=0 t=5 t=10 T
GM M Enterococcus Sterile Sterile G
> 100,000
FP M E. coli Sterile Sterile G
> 100.000
GB F Candida Candida E. coli G
> 100.000 < 50.000 < 50.000
MM M E. coli E. coli Sterile G
> 100.000 < 50.000
MJ F Enterococcus Sterile Sterile E
> 100,000
LC F Candida Candida E. coli G
> 100.000 < 50.000 < 50.000
SL F E. coli Sterile Sterile E
> 100.000
PS F E. coli Sterile Sterile G
> 100.000
RP F Enterococcus E. coli Sterile G
> 100,000 < 50.000
MM M Candida Candida Sterile E
> 100.000 < 50.000
RT F Candida E. coli Sterile G
> 100.000 < 50.000
MF F E. coli E. coli Sterile G
> 100.000 < 50.000
MR F Enterococcus E. coli Sterile E
> 100,000 < 50.000
AR F E. coli Sterile Sterile G
> 100.000
GT F E. coli Sterile Sterile G
> 100.000
Pat = patient; S = sex; T = tolerability; G = good; E = excellent The formulations according to the invention are clearly clinically effective in the treatment of acute cystitis.
It has also been demonstrated that the administration of 400 mg of non- gastroprotected extract containing 30% PAC leads to a very low PAC content in the urinary bladder, not exceeding approx. 1% of the dose administered, whereas the administration of the gastroprotected form at the same dose allows delivery to the bladder area of approx. 60-70% of the dose of PAC administered.
Some examples of formulations according to the invention are set out below. The quantities are expressed as mg/tablet.
Example 1
Microcrystalline cellulose 228,000
Dicalcium phosphate 210,000
Vaccinium macrocarpon (30% Eur. Ph.) 200,000
Crosslinked sodium carboxymethylcellulose 20,000
Glyceryl behenate 20,000
Shellac 15,545
Vegetable magnesium stearate 14,000
Silicon dioxide 8,000
Hydroxypropyl methylcellulose 12,947
E171 2,988
Stearic acid 1,992
Triethyl citrate 1,233
Ammonium carbonate 0,822
Polyvinylpyrrolidone 0,602
El 20 colouring 0,073
El 32 colouring 0,008 Example 2
Calcium pho sphate 50,551
Microcrystalline cellulose 25,000
Vaccinium macrocarpon (80% Eur. Ph.) 200,000 Shellac 35,500
Magnesium stearate 0,900
Glycerin 0,314
Silicon dioxide 0,900
Talc 0,208 Lactose 0,208
Acetylated monoglycerides 0,219
Hydroxypropyl methylcellulo se 0, 104
Polyvinylpyrrolidone 0,073
E124 colouring 0,055 Example 3
Calcium phosphate 68,932
Microcrystalline cellulose 150,000
Vaccinium macrocarpon (30% Eur. Ph.) 500,000
Shellac 20,200 Magnesium stearate 0,850
Glycerin 1, 192
Silicon dioxide 3,500
Talc 0,792
Lactose 0,792 Acetylated monoglycerides 0,219
Hydroxypropyl methylcellulo se 0,396
Polyvinylpyrrolidone 0,073
E124 colouring 0,055

Claims

1. Oral compositions containing type A2 proanthocyanidins in gastroprotected form for the treatment of acute cystitis induced by fimbriated bacterial forms.
2. Compositions as claimed in claim 1 in the form of capsules, tablets, powders or granules coated with natural or synthetic gastroresistant film-forming agents.
3. Compositions as claimed in claim 2 wherein the gastroresistant film-forming agents are selected from shellac and hydroxypropyl methylcellulose.
4. Compositions as claimed in claim 1 wherein the type A2 proanthocyanidins are present in the form of Vaccinium macrocarpon extract.
5. Compositions as claimed in claim 4 containing at least 18 mg of type A2 proanthocyanidins determined by the DMAC assay method (Ocean Spray,
Maryland, USA), or 54 mg determined by a validated method according to the European Pharmacopoeia.
PCT/EP2012/054453 2011-03-15 2012-03-14 Use of type a2 proanthocyanidins in gastroprotected form for the treatment of acute cystitis induced by fimbriated bacterial forms e WO2012123491A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP12717059.5A EP2685967A1 (en) 2011-03-15 2012-03-14 Use of type a2 proanthocyanidins in gastroprotected form for the treatment of acute cystitis induced by fimbriated bacterial forms e

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT000409A ITMI20110409A1 (en) 2011-03-15 2011-03-15 USE OF PROANTOCYANIDINES TYPE A2 IN THE GASTROPROTECT SHAPE FOR THE TREATMENT OF THE CISTITES IN THE ACUTE PHASE SUPPORTED BY FIMBRIED BACTERIAL FORMS
ITMI2011A000409 2011-03-15

Publications (1)

Publication Number Publication Date
WO2012123491A1 true WO2012123491A1 (en) 2012-09-20

Family

ID=43977078

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2012/054453 WO2012123491A1 (en) 2011-03-15 2012-03-14 Use of type a2 proanthocyanidins in gastroprotected form for the treatment of acute cystitis induced by fimbriated bacterial forms e

Country Status (3)

Country Link
EP (1) EP2685967A1 (en)
IT (1) ITMI20110409A1 (en)
WO (1) WO2012123491A1 (en)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106265627A (en) * 2015-06-23 2017-01-04 香港浸会大学 A kind of method treating inflammatory diseases and proanthocyanidin compound are as the medicinal application treating inflammatory diseases
EP3320897A1 (en) 2016-11-14 2018-05-16 Dompè Primary S.r.l Process for the preparation of coated cranberry granules with stable proanthocyanidine content
IT201600122310A1 (en) * 2016-12-01 2018-06-01 Sofar Spa Composition for use in the treatment of bowel disorders
IT201600130012A1 (en) * 2016-12-22 2018-06-22 Neilos S R L Composition for use in the treatment of disorders of the urogenital system
DE102018127408A1 (en) * 2018-11-02 2020-05-07 Ruhrpharm AG Cranberry extract PAC-A composition and its use in the prevention and / or treatment of urinary tract infections
RU2772870C2 (en) * 2016-12-01 2022-05-26 Софар С.П.А. Composition for use in treatment of intestinal damage

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050158381A1 (en) * 2004-01-16 2005-07-21 Mary Aldritt Effervescent composition including cranberry extract

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050158381A1 (en) * 2004-01-16 2005-07-21 Mary Aldritt Effervescent composition including cranberry extract

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
BLATHERWICK J, J BIOL CHEM, vol. 57, 1923, pages 815 - 818
DI PIERRO: "Impiego di un estratto altamente standardizzato e gastroprotetto di Vaccinium macrocarpon Efficacia clinica nelle infezioni vesicali", vol. 12, no. 4, 18 December 2009 (2009-12-18), pages 19 - 23, XP002659147, Retrieved from the Internet <URL:www.monoselect.it/documents/VACCINIUMMACROCARPON.pdf> [retrieved on 20110914] *
DI PIERRO: "Importanza del metodo analitico in fitoterapia Il caso del vaccinium macrocarpon: correlazione concentrazione/ attività", vol. 14, no. 1, 2 March 2011 (2011-03-02), pages 23 - 28, XP002659146, Retrieved from the Internet <URL:http://www.monoselect.it/documents/MonoselectMacrocarpon.pdf> [retrieved on 20110914] *
HOWELL AB; BOTTO H; COMBESCURE C; BLANC-POTARD AB; GAUSA L ET AL., BMC INFECT DIS., vol. 14, 2010, pages 10 - 94
MATSUSHIMA M; SUZUKI T; MASUI A; KASAI K; KOUCHI T ET AL., J GASTROENTEROL HEPATOL., vol. 23, no. 2, December 2008 (2008-12-01), pages S175 - S180
PAPPAS E; SCHAICH KM, CRIT REV FOOD SCI NUTR., vol. 49, no. 9, October 2009 (2009-10-01), pages 741 - 781
PINZON-ARANGO PA; LIU Y; CAMESANO TA, J MED FOOD, vol. 12, no. 2, April 2009 (2009-04-01), pages 259 - 70
ROSSI R; PORTA S; CANOVI B., J CLIN GASTROENTEROL., vol. 44, no. 1, September 2010 (2010-09-01), pages S61 - S62
See also references of EP2685967A1 *

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106265627A (en) * 2015-06-23 2017-01-04 香港浸会大学 A kind of method treating inflammatory diseases and proanthocyanidin compound are as the medicinal application treating inflammatory diseases
EP3320897A1 (en) 2016-11-14 2018-05-16 Dompè Primary S.r.l Process for the preparation of coated cranberry granules with stable proanthocyanidine content
WO2018087351A1 (en) 2016-11-14 2018-05-17 Dompe' Farmaceutici S.P.A. Preparation of coated cranberry granules composition with stable pacs content
RU2766084C2 (en) * 2016-11-14 2022-02-07 Домпе Фармачеутичи С.П.А. Producing cranberry granule composition with sustainable content of proanthocyanidins
WO2018100551A1 (en) * 2016-12-01 2018-06-07 Sofar S.P.A. Composition for use in the treatment of intestinal alterations
CN110430870A (en) * 2016-12-01 2019-11-08 索法尔公司 For treating the composition of intestines change
JP2020500934A (en) * 2016-12-01 2020-01-16 ソファー・エッセ・ピ・ア Compositions for use in treating intestinal changes
US10881703B2 (en) 2016-12-01 2021-01-05 Sofar S.P.A. Composition for use in the treatment of intestinal alterations
IT201600122310A1 (en) * 2016-12-01 2018-06-01 Sofar Spa Composition for use in the treatment of bowel disorders
RU2772870C2 (en) * 2016-12-01 2022-05-26 Софар С.П.А. Composition for use in treatment of intestinal damage
AU2017368931B2 (en) * 2016-12-01 2022-12-22 Sofar S.P.A. Composition for use in the treatment of intestinal alterations
US11690889B2 (en) 2016-12-01 2023-07-04 Sofar S.P.A. Composition for use in the treatment of intestinal alterations
JP7321935B2 (en) 2016-12-01 2023-08-07 ソファー・エッセ・ピ・ア Compositions for use in treating intestinal changes
IT201600130012A1 (en) * 2016-12-22 2018-06-22 Neilos S R L Composition for use in the treatment of disorders of the urogenital system
WO2018116238A1 (en) * 2016-12-22 2018-06-28 Neilos S.r.l. Composition for use in the treatment of disorders of the urogenital apparatus
CN110300616A (en) * 2016-12-22 2019-10-01 内罗斯公司 For treating the composition of the illness of urogenital organ
DE102018127408A1 (en) * 2018-11-02 2020-05-07 Ruhrpharm AG Cranberry extract PAC-A composition and its use in the prevention and / or treatment of urinary tract infections

Also Published As

Publication number Publication date
ITMI20110409A1 (en) 2012-09-16
EP2685967A1 (en) 2014-01-22

Similar Documents

Publication Publication Date Title
JP5700243B2 (en) Compositions comprising starch or dietary fiber from Graminea plant for prevention and treatment of ischemic and brain degenerative diseases
EP3991742A1 (en) Coronavirus therapeutic agent comprising elaeocarpus sylvestris extract as active ingredient
AU2021273627B2 (en) Agent for the prophylactic and/or supportive therapeutic treatment of Parkinson&#39;s disease
WO2012123491A1 (en) Use of type a2 proanthocyanidins in gastroprotected form for the treatment of acute cystitis induced by fimbriated bacterial forms e
US11213535B2 (en) Composition containing phytic acid, magnesium and polyphenols for the treatment or prevention of renal lithiasis
WO2012121140A1 (en) Growth hormone secretion promoter
WO2014010656A1 (en) Superior blood alcohol concentration reduction accelerating agent
JP2013043850A (en) Lipolysis promoter
WO2007009392A1 (en) The use of chlorogenic acid in the manufacturing medicaments for treating and/or preventing hepatic injury
US20160106789A1 (en) Inhibition of Neurodegenerative Disease by Grape Seed Extract, Green Tea Extract and Probiotic Bacteria
JP2022019937A (en) Composition for preventing or treating chronic or acute virus infection and/or sepsis in humans or animals
KR101964054B1 (en) Pharmaceutical composition comprising extract of Lonicera japonica for prevention and treatment of Crohn&#39;s disease
NO20001717L (en) Serotonin-containing formulation for oral administration and use of the same
WO2005044291A1 (en) Grape seed extract having neuronal cell-protecting activity and the composition comprising the same for prepenting and treating degenerative brain disease
JP6257031B2 (en) Prevention or treatment of urinary tract infections
JP3432529B2 (en) Intestinal composition
US20160030493A1 (en) Inhibition of Neurodegenerative Disease by Grape Seed Extract, Green Tea Extract and Probiotic Bacteria
JP2007520431A (en) Hypoglycemic composition
RU2493841C1 (en) Synergetic preparation for treating cardiovascular diseases, diabetes mellitus and hepatobiliary diseases
JP5410152B2 (en) Anemia prevention composition
JP2009298702A (en) Oral administration composition
CN104771591B (en) A kind of medicament for the treatment of chronic gastritis
RU2780346C1 (en) Therapeutic agent against coronavirus including an elaeocarpus sylvestris extract
TWI701035B (en) Uses of fu-ling (poria cocos) extract and tumulosic acid in protecting muscles
JP2007145731A (en) Pharmaceutical preparation for oral administration having stegnotic effect

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 12717059

Country of ref document: EP

Kind code of ref document: A1

REEP Request for entry into the european phase

Ref document number: 2012717059

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2012717059

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: DE