MANNOCIST-D

D-Mannosio 1.5 g

Treatment and prevention
cISTITIES

Medical device CE 0373

INDICATIONS: Mannocist-D envelopes, based on D-Mannosio, is a medical device able to inhibit the adhesion of bacteria responsible for urinary tract infections at the urethral and vescyclical epithelium level, to favor its elimination through urine and thus limit the onset of infections. D-Mannosio can be used both in acute urinary tract infections, and in their relapses. Concurrent use of Mannocist-D with antibiotics and antimicrobial can facilitate the functionality of the latter by increasing patient adherence to therapy.

COMPOSITION: D-Mannosio 1.5 g, sodium bicarbonate, sorbitol, silicon dioxide.

MODE OF USE: acute phase: for the first 3 days, 1 sachet in the morning and 1 in mid afternoon, on stomach and bladder empty; maintenance phase: 1 sachet every morning, on the stomach and empty bladder, until total disappearance of symptoms. If sexual intercourse is the triggering factor of cystitis, take 1 sachet after each relationship and 2 sachets in the next 24 hours, according to the above described methods. Take the product by melting the contents of the sachet in half a glass of water, then do not drink and do not eat for about 40 minutes. During the rest of the day it is important to drink plenty of water to facilitate the elimination of bacteria with urination.

CONTROINDICATIONS: the studies of cytotoxicity, awareness and irritation of the oral mucosa have not seen contraindications.

INDESIDERATE EFFECTS: meteorism phenomena can occur, which usually disappears after a few days.

CONFECT: 20 single-dose bags of 2 g.

• Main features

- CONTRACT STRATEGY OF UTI (Urinary Tract Infection)

- MEDICAL DISPOSITION CLASS II CERTIFICATE BY HIGHER HEALTH INSTITUTE

- D-MANNOTE 1.5 g per MONODOSE

- NO CONTROINDICATION OF USES IN ACCORDANCE WITH BIOCOMPATABLE TESTS
-Citotoxicity
-Allergic sensitization
-Irritation of the oral mucosa.

- PRIVATE OF GLUTINE AND LATTOSIO

- NICKEL TESTED Value detected
• D-Mannosio
D-Mannosio is a simple sugar, an exotic monosaccharide extracted from larch or birch wood with a high safety profile. It is quickly absorbed by the intestine and within a short time (30 min) distributed in the blood and all organs⁽¹⁾. It cannot be transformed into glycogen and therefore is not accumulated in the liver or other organs, nor is it used by the body⁽²⁾. The excess mannose reaches the kidney and bladder and is eliminated with urine. The administration of mannose in the long term, in concentrations up to 20%, has not produced effects on metabolism or signs of toxicity, which supports the good general toxicological profile⁽³⁾.

• D-Mannosio activities on bacteria
Adhesion of bacteria to the surface of animal cells is a crucial factor in virulence and instability of infections. Often this recognition-adhesion is mediated by residues of sugars such as D-Mannosio and L-Fucose that bind to the specific lecitines of the bacterial surface. Several virulence factors are known and described which are more and abundantly represented on pathogenic serotypes for example E.coli (known as UPEC Uropathogenic Escherichia coli), Salmonella spp and other bacteria involved in urinary tract infections such as Proteus mirabilis⁽⁴⁾⁽⁵⁾.

• D-Mannosio in the treatment of UTIs
The bladder wall is covered with various mannosate proteins, including Tamm-Horsfall (THP) proteins, which interfere with the adhesion of the bacteria to the epithelium. The THP binds to E.coli with a highly specific and saturated bond, which is inhibited by D-Mannosio⁽⁶⁾ suggesting an important role of THP mannosilated groups in the specific bond, particularly with pathogenic coles with the FimH virulence factor, which are more abundant in patients with UTI than healthy population. D-Mannosio mimics the functionality of the urothelial barrier, inhibiting the adhesion of bacteria at the urethral and vescic epithelium level. The bacteria, bonding with D-Mannosio molecules free in the urine, instead of nesting in the walls of the mucosa, remain trapped in the flow of urine and with it eliminated. In vitro and alive studies have highlighted the ability of mannosides to reduce the bacterial charge of 2 orders of magnitude in the urine and 4 in the bladder⁽⁷⁾.

• Conclusions
There is a strong and consolidated scientific rational about the effectiveness of D-Mannosio in inhibiting the adhesion of bacteria responsible for UTI, in favoring bacterial clearance through urine and thus reducing the onset of infections^(8-10). The nature of monosaccharide and long-term studies support the fact that it is devoid of toxicity even if ingested at much higher doses than ordinary ones in the diet⁽³⁾.

BUDGET
1. Alton G, Hasilik M, Nieheus R, Fana F and Freeze HH.Direct manipulation of mannose for mammalian glycoprotein biosynthesis. Glycobiology. 1998;8:285-295
2. Sharon N. Carboydrates as future anti-adhesion drugs for infectious diseases Biochim Biophys Acta. 2006 Apr;1760(4);527-37. Epub 2006 Jan 18
3. Davis JA, Freeze HH: Studies of mannose metabolism and effects of long-term mannose ingestion in the mouse. Biochim Biophys Acta, 2001 Oct 3;1528(2-3):116-26
4. Rosen DA. Pinkener JS, Walker JN, Elam JS, Jones JM, Hultgren SJ.Molecular variations in Klebsiella pneumonia and Escherichia coli FimH function and pathogenesis in the urinary tract. Infect Immun. 2008 Jul;76(7):3346-56. May 12, 2008
5. Zunino P., Sosa V, Schalapp G, Allen AG, Preston A, Maskell DJ. Mannose-resistant Proteuslike and P.mirailis fimbriae have specific and additive roles in P.mirabilis urinary tract infections. FEMS Immunol Med Microbiol. 2007 Oct-,51(1):125-33
6. Pak J, Pu Y, Zhang ZT, Hasty DL, Wu XR. Tamm-Horsfall protein binds to type 1 fimbriated Escherichia coli and quotes E.coli form binding to uroplakin Ia and Ib receptors. J Biol Chem. 2001 Mar 30; 276(13):9924-30. Epub 2000 Dec 27.
7. Klein t, Abgottspon D, Witwer M, Rabbani S, Herold J, Jiang X, Kleeb S, Luthi C, Scharenberg M, Bezencon J, Gulber E, Pang L, Smiesko M, Cutting B, Schwardt O, Ernst B. FimH antagonists for the oral treatment of urinary tract infections: from design and synthesis to 2010. Epub 2010 Nov 24
8. Lopez AI, Kumar A, Planas MR, Li Y, Nguyen TV, Cai C. Biofunctionalization of silicone polymers using poly (amidoamine) dendrimers and a mannose derivative for relevance against pathogen colonization. Bimaterials. 2001 Jul;32(19):4336-46. Epub 2011 Mar 24
9. Kim J, Ahn Y, Park KM, Lee DW, Kim K. Glyco-psudopolyrotaxanes: carbohydrate wheels threaded on a polymer string and their inhibition of bacterial adhesion
10.Han Z, Pinkner JS, Ford B, Obermann R, Nolan W, Wildman SA, Hobbs D, Ellenberger T, Cusumano CK, Hyltgren SJ, Jaetka JW. Structure-based drug design and optimization of mannoside bacterial FimH antagonists. J Med Chem. 2010 Jun 24;53(12):4779-92