MXPA97009503A - Bacterial inhibition with a composite of oligosacar - Google Patents

Abstract

The present invention relates to: A method for the treatment of respiratory infections caused by a bacterium selected from the group consisting of S. pneumoniae, H. influenzae, H. parinfluenzae, Burkholderia (Pseudomonas cepacia) and a mixture thereof, by administering an effective inhibitory amount of the compound of the formula (I), wherein R1 is H, (beta-1) GalNAc-, SO3B (where B is H or a cation) or a sialic acid of the formula (II), wherein R6, R7, R8 and R10 are each independently H, C1-C6 acyl, lactyl, C1-C6 alkyl, sulfate, phosphate, anhydrous, a sialic acid of formula (II), (alpha-1) Fuc, (beta-) 1) Glc or (beta-1) Gal, R9 is NH-acyl C1-C6, glycolylamido, amino or hydrotrophic, and A is H or a cation, R2 is H or (alpha-1) Fuc-; R3 and R4 are each independently OH or NHAc, R5 is H, SO3B (where B is H or a cation) or a sialic acid of the formula (II) according to the above defined; and Y is a chemical bond; ico or a linking group, Z is H or a multivalent support, m is 0 or 1, and p is an integer from 1 to 1000, and a pharmaceutical composition containing it.

Description

BACTERIAL INHIBITION WITH A COMPOSITE OF IGOSACARID OL BACKGROUND OF THE INVENTION FIELD OF THE INVENTION The present invention relates to a method for the treatment of bacterial infections caused by a bacteria selected from the group consisting of Streptococcus pneumoniae, Haemophilus influenzae, Hemophilus parainfluenzae, Bur halderia (Pseudomonas) cepacia and a mixture of them using an igosacár ido ol, asi. as a pharmaceutical composition that contains it. BACKGROUND OF THE ART S. pneumoniae, H. influenzae, H. parainfluenzae, and Burkholderia (Pseudomonas) cepacia are pathogenic bacteria associated with respiratory diseases such as pneumonia, bacterial bronchitis, conjuncts, sinusitis and otitis media. In each of these conditions, the bacteria colonizes the healthy tissue of the nasopharynx, conjunctiva, lung, bronchus or ear canal, establishing a population large enough to cause the disease. Bacteria adhere on cell surfaces, in specific receptor sites for bacteria. Conventional therapy has been based on the administration of antibiotics, in order to alleviate bacterial colonization. However, antibiotic therapy faces the development of antibiotic-resistant strains (and may eventually generate "super bacteria") that could not be treated with known antibiotics. A report presented by the American Society sf Microbiology, in May of 1995, indicated that more and more infectious organisms are becoming intractable with antibiotics and that measures must be taken to reverse this tendency before a public health crisis occurs. Researchers have studied the interactions of pathogenic bacteria with tissue receptors, responsible for adherence, and have identified specific carbohydrate sequences that can inhibit bacterial adherence. .rivan et al. in the North American document No. 5,38 ¿> , 027, report the inhibition of binding of "opportunistic pathogenic bacteria", specific, that are associated with respiratory tract infections, with compounds that contain an internal or terminal Ga lNacbetal-4-Ga lbetal-4-Glc sequence. The specific lung pathogenic bacteria for which link inhibition is reported are Pseudo onas aeruginosa, Haemophilus influenzae, Staphylacaccus aureus, Streptocaccus pneumoniae, Klebsiella pneumoniae and Escherichia coli. The reference states that GMl ganglioside is present in substantial amounts in human lung tissue and that pulmonary pathogenic bacteria require at least a 6 terminal or internal lNacbetal-4-Gal that is not substituted with sialloyl residues. Andersson et al J. Exp. Med. (1983), v. 158, p. 559-570, report studies of inhibition of binding in Streptococcus pneumoniae, and identify a disaccharide GlcNac betal-3-Galbeta as a specific glycoconjugate receptor. The reference reports that compound 3, NeuAcal fa2-3Galbet l-4-GlcNAcbetal-3 ~ Galbetal-4-Glc-Cer has no effect on binding inhibition (page 564, first enunciation under Table IV). Rosenstein et al., Infection and I munity (Infection and Immunity) (1992), vol. 60, no. 12, 5078-5084, report binding specificities for Pseudomonas aeruginosa M35 and Escherichia coli C600, isolated from cystic fibrosis patients for various structures of olosaccharides. It was reported that 6albetal-4-GlcNacbetal-3 ~ Galbetal-4-Glc had a high binding activity while NeuAcal fa2-6-Galbetal-4-61cNAcbetal-3-6albetal-4-Glc had no activity. Ra phal et al, Infection and I munity (Infection and Immunity) (1991) vol. 59, no. 2, pages 700-704, report linkage inhibition studies for Pseudomonas aeruginosa for disaccharides type 1 (6albetal-3-GlcNAc) and type 2 < Galbetal-4GlcNAc). It was reported that NeuAcal fa2-6-6albetal-4- GlcNAbetal-3-Galbetal-4-Glc had no activity in the direct adhesion test. Ginsburg et al. in the North American document No. 5, 225,330 report a diagnostic device for the absorption of icroorganisms, using specific carbohydrate receptor sequences. The reference does not report any activity for sial and l paragoboside in Mycoplasma pneumoniae binding inhibition (Table I, column 11) but reports the inhibition of Escherichia coli from N-glycoli and Iloploba wolves gone. Feizi et al Biache istrym (Biochemistry), 1994, 33, 6342-6349, report that NeuAcal fa2-6-Galbetal-4-GlcNAcbetal-3-6 lbetal-4-Glc is not linked or is only loosely bound by the immuno-binding protein lub i 1 ina E, whereas NeuAcal fa2-3-Ga lbet l-3-GlcNAcbetal-3-G lbetal-4-Glc is strongly bound by this protein. Magnani et al in document W092 / 18610 report the use of sialyl-Le (a) (NeuSAcal fa2-3-6albetal-3- (Fucalfal-4) GlcNAc and sialyl-Le (l <;) (NeuSAcalfa2-3 ~ Ga lbetal-4- (Fuca ifal-3) GlcNAc to inhibit the binding of malignant cells on endothelial cells both in vivo and ip vitro Andersson et al., J. of Infectious Diseases (Journal of Infectious Diseases ) (1986), val 153, No. 2, 232-237, report that fractions of human milk inhibited the fixation of Streptacoccus pneumoniae and Haemophilus influenzae on human buccal or pharyngeal epithelial cells, therefore, new methods for the treatment of bacterial infections caused by a bacteria selected from the group consisting of Streptococcus pneumapiae, Haemophilus influenzae, Hemaphilus parainfluenzae, Burkholderia (Pseudomonas) cepacia and a mixture thereof, are being sought, such methods should have a lower probability of generating resistant strains The antiadhesion compounds are potentially useful candidates in this search COMPENDIUM OF THE INVENTION Accordingly, an object of this invention is to provide a novel method for inhibiting the colonization of a bacterium selected from the group consisting of S. pneumoniae, H. influenzae, H. parainf luenzae, Burkholderia (Pseudomonas) cepacia and a mixture thereof by the administration of an effective amount to inhibit the binding of the compound of formula I, < D where R1 is H, < beta-l) 6alNac-, S03B (where B is H or a cation) or a sialic acid of Formula II; where R6, R7, P.8 and RIO are each independently H, acyl Cl-6, lactyl, C1-C6 alkyl, sulfate, phosphate, anhydrous, a sialic acid of formula II, (alpha-l) Fuc, (beta-l) Glc or (beta-l) Gal; R9 is NH-acyl C1-C6, glycol i lido, amino or hydroxyl; and A is H or a cation; R2 is H or (alpha-l) Fuc; R3 and R4 are each independently OH or NHAc; R5 is H, S03B (where B is H or a cation) or a sialic acid of formula II according to that defined above; and Y is a chemical bond or a linking group; Z is H or a very valuable support; m is 0 or 1; and p is an integer from 1 to 1000. A second object of this invention is to provide a method for inhibiting bacterial colonization of a bacterium selected from the group consisting of S. pneumoniae, H. influenzae, H. parainfluenzae, Burkhalderia (Pseudomonas). cepacia and a mixture thereof in a patient who has been diagnosed with pneumonia. Another object of this invention is to provide a method for inhibiting the colonization of a selected bacterium within the group consisting of S. pneumoniae, H. influenza, H. parainfluenza, Burkholderia. { Pseudomonas) cepacia and a mixture thereof in a patient who has been diagnosed with bacterial bronchitis. Another object of the invention is to offer to inhibit the bacterial colonization of a bacterium selected from the group consisting of S. pneumoniae, H. influenzae, H. parainf luenzae, Burkholderia (Pseudomonas) cepacia and a mixture thereof in a patient at which has been diagnosed with otitis media. Another object of this invention is to offer a novel pharmaceutical composition containing a compound of formula I » where R1 is H, (beta-l) SalNac-, S03B (where B is H or a cation) or a sialic acid of Formula II; where R6, R7, R8 and RIO are each independently H, C1-C6 acyl, lactyl, C1-C6 alkyl, sulfate, phosphate, anhydrous, a sialic acid of formula II, (alpha-DFuc, (beta-l) Glc or (beta-1) 6al; R9 is NH-acyl C1-C6, glycol i lido, amino or hydrophilic, and A is H or a cation, R2 is H or (alpha-l) Fuc R3 and R4 are each independently OH or NHAc, R5 is H, S03B (where B is H or a cation) or a sialic acid of formula II as defined above, and Y is a chemical or either a linkage group, Z is H or a strong support, m is 0 or 1, and p is an integer from 1 to 1000 where when P5 is H, R1 is not H and when R1 is a sialic acid , R2 is not (alpha-) was. In a preferred embodiment, the compound of formula I is of the formula wherein Y is a chemical bond or a linking group; Z is H or a non-valent support; is an integer from 1 to 1000. These and other objects of the p The invention is achievable by means of the inventors' discovery that a bacterium selected from the group consisting of S. pneumoniae, H. influenzae, H. parainfluenzae, Burkholderia (Pseudomonas) cepacia and a mixture thereof can be inhibited in relation to colonization, by a compound of formula I. DETAILED DESCRIPTION OF THE PREFERRED MODALITIES The following abbreviations are used in the text: "Gal" for galactose; "Glc" for glucose, "GlcNac" for N-acet i lglucasa ina; "GalNac" for N-ace i lgalactosamine; "It was" for fucasa; "NAN or NeuAc" for a single N-acet i lneura. Specific oligosaccharide compounds can include NeuAlafa2 ~ 6-Galbetal-4-GlcNAcbetal-3-6albetal-4-Glc, NeuAcal fa2 ~ 3-6albetal-4-GlcNAcbetal-3-Galbetal-4-61c, Galbetal-4-GlcNAc : betal-3-6albetal-4-Glc, NeuAcal fa2-6-Galbetal-4-GlcNAcbetal-3-Galbetat-4-Glc, NeuAc l fa2-6- Galbetal-4- < Fucalfal-3) GlcNAcbet 1-3-Ga lbetal-4-Gle, NeuAca lfa2-6- (6 INAcbeta1-3) Galbetal-4-GlcNAcbeta 1-3-Ga lbeta1-4-Glc, NeuAc 1 fa2-6- (Ga INAcbeta 1-3) G lbeta 1-4- (Fuca 1 fa1-3) GlcNAcbeta 1-3-Ga lbeta 1-4-Gl, NeuAc 1 fa2-6-Galbetal-4- GlcNAc, NeuAcalfa2-6-Galbetal-4- (Fucalfal-3) GlcNAc, NeuAca lfa2-6- (G INAcbeta 1-3) G lbeta 1-4-GlcNAc, NeuAca lfa2-6- (G INAcbeta 1-3) 6a lbet 1-4- (Fucalfa 1-3) GlcNAc, Ga INAcbet 1-3-Ga lbet l-4 ~ GlcNAcbetal-3-Galbet 1-4-Glc, Ga INAcbeta 1-3-G 1b tal-4-GlcNAc, G lNacbetal-3-Galb ta 1-4-Glc, NeuAca lfa2-3 ~ Galbet 1-4-GlcNAc, NeuAcal fa2-6-6a Ibet l-4-GlcNAcbeta1-3-Ga lbetal-4-GlcNAc, NeuAcalfa2-3 -Ga lbet 1-4-GlcNAcbeta1-3-Ga lbeta 1-4-GlcNAc, G lbetal-4-GlcNAcbetaí-3-Galbetal-4-GlcNAc, NeuAcal fa2-6-Ga lbeta 1-4- (Fucal f l- 3) 61cNAcbetal-3-Galbetal-4-GlcNAc, NeuAca 1 fa2-6- (Ga INAcbet 1-3) 6albetal-4-GlcNAcbetal-3-6a lbet 1-4-GlcNAc, NeuAcalfa2-6- (GalNAcbetal-3) Galbetal-4- (Fucal fal-3) GlcNAcbetal-3-Galbe al-4-GlcNAc, Ga INAcbe to 1-3-Ga lbet 1-4-GlcNAcbetal-3-Galbetal-4 ~ GlcNAc, and Ga INAcbeta 1-3 -Ga lbetal-4-GlcNAc. A preferred group of igosaccharide compounds are the groups identified above, excluding the compound Ga lbeta1-4-GlcNAcbe at 1-3-Ga Ibeta 1-4-Glc. Each of these compounds can also be administered in monovalent form (ie, p = 1) or in the form of a lens (ie, p ~ 2 - 1000), either with or without a Y-linking group. , the linking group Y can be linked directly to Z where Z is H, or a lens support. Olosaccharides of the present invention can be obtained using any known method, including (1) in magnetically, using one of the methods described in US Pat. No. 5,180,674, (2) synthetically, using classical organic chemistry, (3) by degradation of an oligosaccharide, glycolipids, or glycopeptide that occurs naturally or (4) by isolation from a natural source with, for example, human milk. The isolation of LSTc is reported by Kuhn, R. and Gauche, A, Chem Ber., 95, 513 (1962) and Dorland et al. Eur. J. Bioch. 87, 323 (1978). For example, the NeuAcal compound fa2-6-6albetal-4-GlcNAcbeta 1-3-G lbetal-4-61c can be prepared enzymatically from lactose. Consequently, lactose reacts with a β-galactoside beta 1-3 N-acetylglucanase in i iransferase and UDP-GlcNAc, a beta N-acet i Iglucosaminoside betal-4 galactssi 1 transferase and UDP-Gal and beta-galactoside alpha2- 3 sial i 1 ransferase and CMP-NeuAc under conditions suitable to affect the transfer of the three sugar groups from the nucleotides of sugars to the appropriate acceptor molecule. The groups R1 and R5 can be a group S03B, where it can be either H or a cation. Accordingly, the compound of the formula I includes a sulfate substitute and salts thereof. Suitable cations include alkali metals, alkaline earth metals or ammonium. Any suitable pharmaceutically acceptable cation can be employed, including conventional toxic salt cations including a metal salt such as an alkali metal salt (eg, sodium salt, potassium salt, etc.) or a metal salt of alkaline earth (for example calcium salt, magnesium salt, etc.), an ammonium salt, a salt of an organic base (for example a trimethylamine salt, triethylamine salt, pyridine salt, picoline salt, salt of dicyclohexy lamin, salt of N, N'-dibencilet and lendiamin, etc.), an organic acid salt eg, formate, acetate, tri-f luoroacetate, maleate, tartrate, etansul phonata, benzenesulfonate, toluensul fonate, etc. ), a salt of inorganic acid (for example hydrochloride, hydrobromide, sulfate, phosphate, etc.) a salt with an amino acid (for example arginine salt, salt of aspartic acid, salt of glutamic acid, etc.), and the like . The compound of the formula I can also be the corresponding aza sugar, wherein the oxygen of one or more of the pyran rings is replaced by a nitrogen, to form a ring system of piperidine. The aza sugars corresponding to the formula I can be prepared by conventional methods known to those with certain knowledge in the art such as, for example, by classical organic chemistry techniques or enzymatically using the appropriate aza saccharide or acceptor substrate. The aza sugar nucleotides can be transferred by means of the corresponding glycosyltransferase for the natural sugar. Aza glucose can be isolated from natural sources and can be converted to lactose aza by the action of a galactosyl transferase in the presence of a galactose bed donor eg UDP-gal. The compound of formula I can also be the corresponding tio sugar, wherein the oxygen of one or more of the pirana rings is replaced by a sulfur to form a tetrahydrotopyranous ring system. The thio sugars corresponding to the formula I can be prepared by conventional methods known to those with certain knowledge in the art, such as, for example, by classical organic chemistry techniques or enzymatically, using thiosacharide as the acceptor substrate. Opot iosaccharide can be prepared by conventional classical organic-chemistry techniques from the corresponding monosaccharide. The compound of formula II is a sialic acid, which is a family of carboxylated sugars of 9 carbon atoms related to neuraminic acid. The carboxylic acid can be in the form of a free acid, where A is H or a salt, where A is a cation. Suitable cations include alkali metals, alkaline earth metals, or ammonium. Any known suitable pharmaceutically acceptable cation can also be employed, including the cations of conventional non-toxic salts including a metal salt such as for example an alkali metal salt (eg, sodium salt, potassium salt, etc.) or a salt alkaline earth metal (for example calcium salt, magnesium salt, etc.), an ammonium salt, a salt of an organic base (for example a trimethylamine salt, triethylamine salt, pyridine salt, picoline salt, sodium salt). iciclohe i lamina, N, N'-dibencium and lendiamine salt, etc.), an organic acid salt (eg, formate, acetate, tri-f luoroacetate, maleate, tartrate, ethanesulfonate, benzenesul fonate, toluensulphone or, etc.), a salt of inorganic acid (e.g. hydrochloride, hydrobromide, sulfate, phosphate, etc.) a salt with an amino acid (e.g., arginine salt, salt of aspartic acid, salt of glutamic acid, etc.), and Similar. Preferably, the cund of the formula II is selected from the group consisting of N-acetyl-neuraminic acid, N-glycolic acid 1-neuraminic acid, keto-deoxy-nonsulonic acid, 9-0-acetyl acid N- acet i 1-neuraminic acid, 9-0-acetyl N-glycolic acid, 9-0-acet i 1-keta-desaxi-nonulosonic acid, 7-0-acet i 1-N-aceti l acid Neuraminic, 7-O-acetyl 1-N-glycol il-neuraminic acid, 4-0-acetyl-N-acetyl-1-neuraminic acid, 4-0-acetyl 1-N-glycol and 1-neuramyl acid nica, 7,9-di-Q-aceti 1-N-ace i 1-neuraminica, 8,9-di-0-aceti 1-N-acetyl-ne-ramínica acid, acid 7,9-di-0 -acety 1-N-glycol i-neuraminic acid, 8,9-di-0-acet i 1-N-glycol i 1- neura, acid 4,9 ~ di-0-acet i 1-N -aceti-1-peuramyl, 7,8,9-tri-O-acetyl-N-acetyl-neuraminic acid, 7,8,9-tri-0-acet-1-N-glycol-1-neuraminic acid , 9-0-lact i 1-N-ace-il-neuraminic acid, 9-0-lact i 1-N-gly-i l-neuraminic acid, 4-0-aceti 1-9-0-lacti 1- acid N-aceti l-neuram unique, 4-0-acetyl 1-9-0-lactyl-N-glycol i i-neuraminic acid, 8-0-methyl-N-acetyl-neuraminic acid, 8-0-met i 1-N acid -gl icol i l-neuraminic, 8-0-me il-9-0-aceti 1-N-glycol l-neuraminic acid, 8-0-met i 1-7 acid, 9-di-0-acet il-N-gly-il-neuraminic acid, 8-0-sulfo-N-glycol-1-neuraminic acid, 8-0-phosphorus-N-acet-1-peuraminic acid, 2,3-dideh acid, 2-idro 6-anh idro-N-aceti 1-neuraminic, acid 9-0-acet i 1-2, 3-didehydro 2,6-anhid or N-acet i l-neuraminic, acid 9-0-lact i 1-2, 3-didehydro 2,6-anhydrous-N-acetyl-neuraminic, 2,3-didehydro-2,6-anhydro-N-glycol 1-neuraminic acid, 9-0-acetyl-2,3-didehydro acid, 2 , 6 anhydro-N-glycol l-neuraminic acid, 9-0-lactyl-2,3-didehydro-2,6-anhydro-N-glycol l-neuraminic acid, 8-0-met i 1-2,3 acid didehydro 2,6-anhydro-N-glycol lino-neuraminic acid, 2,7-anhydro-N-acet-1-neuraminic acid, 2,7-anhydro-N-glycol-1-neuraminic acid, 8-0-methylated acid 1-2,7 anhydro-N-glycol il-neuraminic, acid 4.8 anh ihdro-N-acet i 1- neuraminic and salts thereof. The most preferred sialic acid of formula II is N-acet and Ineuraminic acid or N-glycol and Ineuraminic acid. These sialic acids are described in A. Varki Glycobiology v2, (1992) p. 25-40. Accordingly, the reference describes sources of the sialic acids as well as the appropriate sial i 1 transferase necessary for the enzymatic synthesis of the igosaccharides of the formula I. When the cund of the formula II is substituted with a sialic acid, the substitution is preferably in the R7 position. The linking group Y is any group which serves to link the igasaccharide portion of the cund of the formula I with the group Z. Suitable linking groups include saccharides, the igasaccharides, peptides, proteins, C2-C20 alkyl, oxyalkylene or any other group which does not decrease the binding inhibition activity of the igasaccharide moiety of the cund of formula I. In addition, the linking group may be a chemical bond, in which case the oligosaccharide portion thereof. The cund of the formula I is directly linked to the group Z.

Olosaccharide can be provided in the form of a final molecule according to formula I (ie p = 2-1000). In this modality, the igosaccharide portion is bound on a multivalent support using known techniques in order to produce a conjugate wherein more than a single oligosaccharide molecule is covalently fixed through the group Y, on the support multi valepte. The multivalent support is sufficiently long to provide a multivalent support having between 2-1000 (ie, p = an integer comprised between 2 and 1,000), preferably 2-100, more preferably 2 to 50 portion molecules of igosaccharide united on the multi-purpose support. A suitable multivalent support is a compound with multiple binding sites, on a terminal end of the linking group that is not linked to the reducing end saccharide, or with multiple binding sites with the identical glycic oxygen Cl of a residue of glucose or N-acetyl glucosamine. Examples include, but are not limited to, polyol, polysaccharide, palilysin, avidin, polyacrylamide, dextran, lipids, 1-lipid emulsions, liposomes, dendrimer, human serum albumin, bovine serum albumin or cyclysdextrin. The chemical process necessary to bind the reducing end saccharide (i.e., 61c or GlcNAc) with the linking group Y and to link the linking group Y on the multivalent support is well known in the field of link chemistry. . For example, a link between the reducing end saccharide and Y can be formed by the reaction of an aldehyde or carboxylic acid in Cl of the reducing end saccharide or any aldehyde or carboxylic acid group and produced in the reducing end saccharide. by oxidation, with the group Y, to form a suitable bond such as for example -Ur ^ ~, -N (P ') -, where R' is C1-C20 alkyl, a hydroxyalkyl plate, an amide, an ester, a thioester , a thioamide. The bond between the reducing end saccharide and Y can be formed by the reaction of the hydroxyl Cl group, in the pyranose form, with an allylation agent and a molecular halide, followed by reaction with a nucleophile to form a suitable bond as per example NH-, -N (R ') - where R 1 is C 1 -C 20 alkyl, -S- and -O-. This type of binding chemistry is described by Stowell et al in Adv nees in Carbohyd te Chemistry and Biachemistry (Advances in the Chemistry and Biochemistry of Carbohydrates), 37 (1980), p 225 et seq. The oligosaccharide portion can be directly bonded (i.e. Y is a chemical bond) on the multivalent support through the free anomeric carbon of the reducing end saccharide. Alternatively, the reducing end saccharide may be linked via a fenet and laminate isocyanate derivative in accordance with that described by Sith et al. in Complex Carbohydra is part C. Methods in Enzy ology, (Carbohydrates complex part C, Methods in Enzyme), volume L, published by V. Ginsburg (1978), pages 169-171. It is preferable that the igasaccharide ol of formula I remains soluble in water. However, it is also possible to administer the oligosaccharide of formula I in the form of a suspension in a suitable vehicle. The method of inhibiting bacterial colonization is achieved by administering an effective amount to inhibit the binding of the oligosaccharide of formula I to a patient in need of such administration. The method of administration will depend on the desired site of oligogosaccharide delivery. For example, to treat respiratory infections, the igasaccharide ol is administered to the nasopharynx, lung or bronchi preferably in the form of an aerosol. To treat otitis media, olosaccharide is administered to the nasopharynx, preferably in the form of drops. To treat the conjuncti itis, the igosaearid ol may be administered to conjunctive tissue, preferably in the form of eye drops or eye ointment. Suitable compounds may take the form of a solution, suspension or any pharmaceutically acceptable form suitable for delivery to the site of infection, especially the lungs, bronchial passages, nasopharynx or middle ear. Olosaccharide can also be administered to the lungs and the bronchial passage in the form of a dry, aerosol-like powder. The pharmaceutical compositions are usually administered in a mixture with a suitably selected vehicle according to the route of administration, using standard formulations. A solution or suspension can be prepared by the addition of any usual diluent used in the art. For example, suitable diluents include water (bacteriostatic, sterile and / or pyrogen-free), ethyl alcohol, propylene glycol, polyoxiet and lensorbi tol, and sorbitan steres. Sodium chloride, glucose or glycerol can be incorporated into said liquid preparation in an amount sufficient to prepare an isotonic solution. Olosaccharides of formula I can also be administered in combination with an antibiotic with activity against a bacterium selected from the group consisting of S. pneumoniae, H. influenza, H. for inf luenza, Burkholderia (Pseuda onas) cepacia and a mixture thereof. Examples of suitable classes of antibiotics include aminoglycosides, phenolics, ansamycins, beta-lactams, for example carbapenems, cephalosporins, cefamycins, monobactams, oxacephems and penicillins, 1 incosamides, acroids, polypeptides, tetracyclines, 2,4- Inopi rimidines, nitrofurans, quinolanas, sulfonamides, sulfones, beta-lactamase inhibitors and antifungal antibiotics such as palienos. Specific examples of suitable antibiotic compounds include, without limitation, etronidazole, tetracycline, bismuth, erythromycin, sulfonamide, penicillin, cephalosporin, amo? Icilin, cycloserine, fosfsmycin, vancomycin, bacillin, polyxin, itomycin, novobiocin, actinicin, rifampicin, indamycin, lincomycin, isoniazid, flucytosine, claramiphenyl, pure ieine, fusidic acid, griseafulvin, p-aminosalic acid, trimeptim, imipenem. Suitable antibiotics also include antibiotic compounds identified in the Merck Index, Eleventh edition, (Merck index, key edition), especially those listed in the THER-9, THER-10 and THER-13 pages, whose total content is Incorporated here by reference. The amount of antibiotic administered in combination with the olosaccharide present is approximately the same amount administered for its known therapy. Accordingly, the effective dosage of the antibiotic can be determined by routine experimentation. The therapeutic composition may also contain customary dissolving aids, regulators, pain relieving agents, preservatives of the art, and optionally, coloring agents, flavors, flavors, sweeteners, and other pharmacologically active agents as are well known in the art. . The pharmaceutical compositions are preferably formulated to provide an isotonic solution. The pH of such compositions is preferably from 6 to 8, preferably from 6.8 to 7.7, and with a higher degree of preference at a physiological pH. Typically, suitable patients are human beings. However, the present method can also be applied to the treatment of animals, including, but not limited to, mammals such as pigs, cows, horses, goats, dogs, cats, rodents and non-human primates. In accordance with a preferred embodiment of the present invention, the oligosaccharide containing a pharmaceutical composition is administered in aerosol form to a patient requiring such administration to inhibit the binding or eliminate colonies of a selected bacteria within the group consisting of of S. pneumoniae, H. influenzae, H. parainfluenzae, Burkholderia (Pseudomonas) cepacia and a mixture of these from the throat, conjunctiva, lungs or bronchial passage of the patient. For aerosol administration, the oligosaccharide compound of the formula I is preferably supplied in a finely divided form together with a surfactant and an impeller. Typical amounts of the igosaccharide ol of formula I are from about 0.5 to 30 * 4 in weight, preferably approximately 1 to 10 * in weight. The surfactant is non-toxic and preferably soluble in the impeller. Representative of surfactant agents are the esters or partial esters of fatty acids containing from 6 to 22 carbon atoms such as for example caproic, octanoic, lauric, palmitic, stearic, linoleic, lonolénico, allestérieo, and oleic acid, with a polyhydric alcohol aliphatic or its cyclic anhydride such as for example ethylene glycol, glycerol, erythritol, arabital, mannitol, sarbitol, the hexitol anhydrides derived from sorbitol, and the polyoxyethylene and palyoxipropyl derivatives of these esters. Mixed esters, such as natural or mixed glycerides, can be used. The surfactant may constitute from about 0.1 to about 20 * 4 by weight of the composition, and preferably from about 0.25 to about 5 * 4. The balance of the composition is ordinarily impelling. Liquefied impellers are typically gases in ambient conditions, and condensed under pressure. Among the suitable liquefied impellers are lower alkanes containing up to 5 carbons, such as butane and propane; and preferably fluorinated or fluoroalorinated alkane such as for example R-ll. Mixtures of the above can also be used. When producing the aerosol, a container equipped with a suitable valve is filled with the appropriate impeller, which contains the finely divided compounds and the surfactant. The ingredients are maintained in this manner under high pressure until their release by means of the valve actuation. For administration as an aerosol, the generation of said aerosol is achieved by means of conventions known to persons with certain knowledge in the technique of drug delivery. When administered in the form of an aerosol in monovalent form, for the treatment of respiratory infection, the composition is formulated to offer a concentration in the mucous membranes of 0.0001 to 20 mg / mL, preferably 0.01 to 10 mg / mL. . When administered as a multivalent molecule for the treatment of a respiratory infection, an aerosol pharmaceutical composition comprising the olosaccharide of formula I is administered in order to achieve a concentration in the mucous membranes of 0.00001 to 2 mg / mL, of Preference from 0.001 to 1 mg / mL. According to another embodiment of the present invention, the pharmaceutical composition containing the olosaccharide ol is administered through the nasopharynx to the ear of a patient requiring said administration to inhibit the binding, or to eliminate colonies of selected bacteria within the group Which consists of S. pneumoniae, H. influenzae, H. parainfluenzae, Burkholderia (Pseudomonas) cepacia and a mixture thereof of a middle ear of a patient. A patient who requires such administration is typically diagnosed with mid-ortitis. The mode of administration is such that an effective amount is provided to inhibit the binding of the olosaccharide of formula I to the site of infection. This can typically be achieved by administering nasal drops or spray containing the olosaccharide of formula I, through the nasopharyngeal, into the ear. The oligosaccharide of formula I can also be administered in the form of an oral mouth rinse, wherein the igosaccharide is delivered to the site of infection by the action of gargling and refluxing. When administered to the ear, a suitable form is a liquid solution or a suspension in a non-toxic pharmaceutically acceptable diluent or solvent, for example, in the form of a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that can be used are water, Ringer's solution and an isotonic sodium chloride solution. In addition, sterile fixed oils are conventionally employed as a solvent or suspension medium. For this purpose, any soft fixed oil may be employed including monoglycerides or synthetic diglycerides. In addition, fatty acids such as oleic acids can be used for the preparation of injectable substances. When administered to the ear in monovalent form, for the treatment of ortitis media, the composition is formulated to provide the concentration at the site of infection of 0.0001 to 20 mg / mL, preferably 0.01 to 10 mg / mL. When administered in the form of a multivalent molecule for the treatment of ortitis media, the composition is formulated to provide a site-of-infection concentration of 0.00001 to 2 mg / mL, preferably 0.001 to 1 mg / mL. According to another embodiment of the present invention, the olosaccharide-containing pharmaceutical composition is administered to the eye of a patient requiring such administration to inhibit the binding or to eliminate colonies of a bacteria selected from the group consisting of S. pneumoniae, H. influenzae, H. parainfluenzae, Burkholderia (Pseudamanas) cepacia and a mixture thereof from the eye of a patient. A patient who requires such administration is typically diagnosed with a conjunctivitis. When administered to the eye, a suitable form is a liquid solution or suspension in a non-toxic pharmaceutically acceptable diluent or solvent, for example, in the form of an ophthalmic saline solution. When administered to the garlic in a monovalent form, for the treatment of with an itis, the composition is formulated to provide a concentration at the site of infection of 0.0001 to 20 mg / mL, preferably 0.01 to 10 mg / mL. When administered in the form of a multivalent molecule for the treatment of conjunctivitis, the composition is formulated to provide a concentration at the site of infection of 0.00001 to 2 mg / mL, preferably 0.001 to 1 mg / mL. These dosages can be achieved by administration, at least daily, preferably twice a day, more preferably three times a day and with special preference four times a day. The present invention can also be used to prevent a bacterial infection of S. pneumoniae, H. influenzae, H. parainf luenzae, Burkholderia (Pseudamana) cepacia in a patient who requires it. While it is generally desirable to avoid bacterial infection in all asymptomatic patients for a bacterial infection, there is an identifiable population for which the consequences of a bacterial infection make the risk of a bacterial infection unacceptable. Specifically, the consequences of a bacterial infection in young, elderly or immunocompromised patients are specifically severe. Accordingly, the oligosaccharide of formula I can be administered to a patient who requires the prevention of a bacterial infection of S. pneumoniae, H. influenzae, H. parainf luenzae, Burkholderia (Pseudomonas) cepacia in an amount sufficient to avoid the bacterial infection. For the prevention of a respiratory bacterial infection, the igasaccharide ol of formula I typically administered in monovalent form to provide a concentration in the mucous membranes of 0.0001 to 20 mg / mL, preferably 0.01 to 10 mg / mL. These prophylactic dosages can be achieved by administration, at least daily, preferably twice a day. When administered as a final lens molecule for the prevention of a respiratory infection, an aerosolized pharmaceutical composition comprising the olosaccharide of the formula I is administered in order to achieve a concentration in the mucous membranes of 0.00001 to 2mg / mL. , preferably from 0.001 to 1 mg / mL. When administered through the nasopharynx to the ear for the prevention of ortitis media, the composition is formulated in a monovalent form to provide the concentration in the ear membranes of 0.00001 to 20 mg / mL, preferably 0.01 to 10 mg. / mL. When administered through the nasopharynx in the form of a multivalent molecule to the ear for the prevention of artitis media, for the treatment of ortitis media, a composition comprising the oligosaccharide of formula I is administered in order to achieve a concentration in the ear membranes from 0.00001 to 2 mg / mL, preferably from 0.001 to 1 mg / mL. The pharmaceutical composition of the invention is basically in accordance with what is described above for the inhibition of bacterial infections. The amount of olosaccharides of formula I will vary according to the mode of administration, based on the amount needed to deliver an effective amount of inhibition of binding to the site of infection. Generally the pharmaceutical substance will contain the olosaccharide in a concentration of approximately 0.01 to 2,000 mg / mL, preferably from 1 to 1,000 mg / mL, in monovalent form, and from 0.001 to 200 mg / mL, preferably from 0.1 to 100. mg / mL, in multi-alente form. Other characteristics of the invention will be apparent in the course of the following description of exemplary embodiments that are provided for the purpose of illustrating the invention but not limiting it.

In the examples section, the following abbreviations will be used: LSTc: Ne? Acalfa2-6-Ga lbet 1-4-GlcNAcbet 1-3-Galbeta 1-4-G c LNnT: G 1beta 1 -4-6IcNAcbeta 1-3 -Ga ltabe 1-4-Glc LSTd (3'LSTc): NeuAcalfa2-3-Galbetal-4-61cNAcbetal-3-6albetal-4-Glc GalNAc betal-3 LNnT: 6alNAcbetal-3-Galbetal-4-GlcNAcbetal-3 Galbetal-4-Glc HSA: human serum albumin Example 1 Synthesis of NeuAc lfa2-6-6a lbeta l-4-GlcBAcbetal-3-6a lb tal- 4-Glc Lactose was contacted with UDP-N-acet i lglucosamine and beta-galactoside betal-3 N-acetyl glucosamine 1 transferase purified from pig serum in an aqueous solution regulated with 0.1 M HEPS at 37 ° C. The trisaecharide of the product was then contacted with UDP-Gal and a beta-N-acetylglucosaminoside betal-4 Galactosi 1 transferase isolated from bovine milk, in an aqueous solution regulated with 0.1 M HEPS at a temperature of 37 ° C. . The tetrasaccharide of the product was then contacted with CMP-NAN and a beta-galactoside alpha2-6 sial i 1 transferase isolated from rat liver in an aqueous solution regulated with 0.1 M HEPES at a temperature of 37 ° C. The pentasaccharide was isolated by conventional methods. Example 2 A method similar to that of Rostand, K. and Esko, (1993) J. Biol. Chem. 268 pp 24053-3, which studied the binding of P. aeruginosa radiated arcade on CHO cells to test link inhibition was employed. of compounds of igosacár ido. For the studies described here, S. pneumoniae (strains R-6, P70, and other clinical respiratory isolates) were labeled by lysine-deficient soy culture broth containing 3H-lysine. Tryptic soy broth became deficient in lysine by pretreatment with decarbaxylase of lysine from E. coli. The bacteria were cultivated for 4-5 hours, at this time the crop was in exponential growth. Bacteria were harvested and washed in a Leibovitz L-15 medium supplemented with 0.2 * 4 bovine serum albumin with low level of endotoxins. The bacteria were diluted to approximately 3 x 100,000,000 / mL, and then mixed either with L-15-BSA or with several compounds to be tested. The bacterial mixtures were incubated at room temperature, with gentle agitation in an orbital shaker. After 10-15 minutes, the samples of the bacterial mixtures were transferred to the surface of a confluent monolayer of cultured epithelial cells in a 96 well polystyrene dish. The most frequently used cells were those derived from Wong-Kilbourne of Chang conjunctiva. The Detroit 562 human nasopharyngeal cell line, and the human lung cell line A549 were also employed. The bacteria were incubated with the cells for 30 minutes with gentle agitation, at room temperature. The unbound bacteria were removed by washing with FBS containing 0.2 * 4 bovine serum albumin. A scintillating solution was added to the wells, and the dishes were placed in a microplate scintillation counter for quantification of the bound bacteria. The adherence of H. influenzae on the epithelial cells was carried out with the same protocol with the following modifications: the bacteria were cultured overnight in a lysine-deficient Haemophilus test medium. The bacteria were incubated with the cells at a concentration close to 10,000,000 / mL for 60 minutes. IC50 (mM) LSTc Bacteria Det-FaDu CaLu 1 'lung A549 HUVEC CHANG 562 -3 S. pneumoniae 5.4 4.0 4.4 0.4 0.1 0.1 0.1 1.5 P. cepacia 1 Lstc-HSA (3) Bacteria Det- FaDu CaLu 1 'lung A549 HUVEC 562 -3 S. p eumoniae 0.10 .0004 H. influenzae 0.03 Det-562 and FaD?: Nasopharyngeal carcinomas CaLu-3 and A459 (l): lung carcinomas 1 * lung: primary epithelium of rat trachea HUVEC (2): endothelial cells of the human umbilical vein (1) cells activated with IL-alphafa (2) cells activated with TNFalpha or thrombin (3) LSTc linked to a structure of human serum albumin; the molar ratio between igosacár ido and prat = 20: 1. The modality of the igosaccharged ol is provided. Inhibition of the adhesion of S. pneumoniae sotare respiratory epithelial cells UC50 (M) (mean (standard deviation)) Monov lens CELLULAR LINE (1) Det- FaDu CaLu 1"lung A549 HUVEC Chang 56; (2) (3) LNnT 7.0> 16.0 0.095 0.052 8.0 (0.005) (0.022) LSTc 4.0 4.5 4.4 0.25 0.069 0.069 1.4 (0.032) (0.035) LSTd O .095 O. 90 O.6 (3 'LSTc) (0.005) GalNAc O.080 O. 75 betal-3 LNnT GalNAc 0.085 0.070 > 6.0 betal-3 6albetal-4 Glc Multivalent (4) CELLULAR LINE (l) Det- FaDu CaLu 1"lung A549 HUVEC 562 -3 (2) (3) LNnT 0.500 0.100 0.030 (0.020) LSTn 0.125 0.160 0.110 0.250 0.021 0.023 (0.006) (0.012) GalNac betal- 0.500 0.020 0.100 0.0004 0.100 0.087 3 Gal-HSA (0.018) 1. Detr «p r -r? 6? and F iD ?: > -? \ ~ > moma na _u f a r i? QO linfiup Cat.t »^ > 4C ?:: > at > mom-i pnl omr tt? m..n > - > HtJVEC f • elfil ^ rn n.-n'J '> l? Jl i .1"? =? - ^ 1 -i yf'iid nmli i 1? - -i 1 l? < ii rií í p T m > -tr J =) '1" pul óii ouo af > i t > 1 i to 1 of i ta uea < -) -i • ip (ti I irnu t- - Ch ng: carci a c. Onjunt i val human 2. ac ti vado on II llfa 3. aclivi o with TNFa] fa or tromluna 4. structure of human serum albumin proportion of poorly educated and pro = 1. They are provided): • molar concentrations of money. ^ p tis, E iem 1 or 3 E; μer imento? I live with LSTc and L t. T Rabbits. = _ =: -. AI I • J * = »S. IHI UJIO? I? Ti ti-i n m -.-? 1 = ¡J 3 r n ol ígosac áp os y ad i ni?, < rad? s a ofiejuñ blan > . _ > s d * u '- ^ Zeeland by insl onion in the ti qnei, and, of the lung were counted at the time indicated by the method described in Saul 1-onen et al. , 1991, J. E "p. Med. 173: 1143-9. Colonization of rabbit lungs with S. pneumomae in the presence of an olosaccharide ol that inhibits adherence.

CFU * Conditions LSTc (100 μM) LNnT (100 μM) control (solution sa 1 ina) 1. Inoculum: 5x100,000 1.4x100,000 8.7x100 7.5x10,000 bacteria; 9.1x1000 4.7x1000 7.1x10,000 intratraquea1; washing at 24 h. washing at 4 days < 10, < 10 < 10, 10 1.6x10,000 4.5x1000 2. Inoculum: 5x100,000 0, 0 0, 0 1.6x10,000 bacteria 4.5x1000 int r trachea 1; washed at 4 days 3. Inoculum: 5x10,000,000 0, 0 0, 0 3.1x100,000 bacteria ** intra raquea 1; 2.2x10,000 wash at 24 hours 4. Inoculum: 100,000 1.1x1000 1.4x100,000 bacteria: 1.4x1000 1.4x100,000 intratracheal: wash at 24 hours * The lungs were washed on day 4 and the fluid was plated quantitatively on blood agar for counting the bacterial colonies / ml of wash fluid. 2 rabbits / group. ** Control animals with saline that received this high inoculum became ill, with highly colonized lungs. One rabbit was bacterial (10,000 CFU / ml of blood). The animals treated with olosaccharides remained healthy throughout the experiment. EXAMPLE 4 Treatment of pre-colonized rabbits with S. pneumoniae with oligosaccharides of adhesion reversion. The strain AI I of S. pne? Oniae was administered to white rabbits from New Zealand using tracheal inspiration. All rabbits were sick at 24 hours, with indications of pneumonia. After 24 hours, it was administered intratracheally between igosaccharides (LNnT) or control (saline). After an additional 24 hours, the lung lavage colonies were counted according to that described in example 3.

CFU Conditions LNnT (lOOμM) Control (s. Salt ina) Inoculum: 100,000 bacteria 0.0 5.4x1000, 4.8 x intratrache wash 1 at 1000 24 hours after treatment with ileosaccharide and 48 hours after bacterial installation.

At 48 hours, the rabbits treated with LNnT were healthy, whereas the control rabbits that received the saline solution were sick, with inflamed, bloody lungs. Example 5 Rats: Newborn Sprague-Dawley rats were inoculated with 1,000,000 S. pneumoniae strain SI 11 intranasally in a volume of 20 μl of saline. At the indicated time the nasal quality was washed and placed on blood agar in serial dilutions to determine the number of colonies. Colonization of rat nasopharynx with S. pneumoniae in the presence of an igasaccharide ol that inhibits adherence CFU * Conditions LSTc-HSA LNnT-HSA Control (100 μM) (100 μM) (saline) 1. In ass: 1,000,000 4.1 (± 1.0) x 3.5 (± 0.4x 8.8 (± 0.8x bacteria, 10,000 10,000 10,000 i tratraquea 1; 4 rats / group; nasal lavage at 3 hours nasal lavage at 3 ± 1 6 ± 1 268 ± 62 at 7 days 2 Ic1 1: 1, OOO, OOO 4.1 (t .8) "i .7 (+.) 8.3 (1 .8): - ba >; na. - »; 1, 0O 1, OOO io, 000 jn ra t raque * .1; the ado?? Aal" t. 5 h * t cavity ttas.il fnn washed in ln- ~ _; indicated times and -.o determined > - ?! CFU number / ml wash fluid. E jem o 6 Employ or the test protocol described in -1 example 2, e tested four ce to the bacterium for 1-3 inhibition of nlare by di ferente.io pu st - "-» e ol i gosa "Inh ibt" i i i (((((((((((((((((((-¡ -¡ -¡ -¡ -¡ -¡ -¡ -¡ -¡ -¡ -¡ -¡ -¡ -¡ -¡ -¡ -¡ -¡ -¡ -¡ -¡ -¡ -¡ ep ep ep ep ep ep ep ep ep ep ep ep ep -? Ion as IC 0 ímM) (ine i (des ia ión es án ar)) Bacteria H. i nf luenr e H. infl uen,: ae H. par- inf lu nrit '? (strain 4651) te »μa 39689) (strain 4 243) CELLS Ch ny Cha ng DE T -'-. ?? I nT 14.0 »14. or L« _- 1 r - 1? . or GalN r b > ta 7.8 < ? ) or. or 1-3 LN t Ga l NAi b < ? ta 4.2 i 5.) HJ. (7.7) 1-3 Gal beta 1-4 Glc LNnT-HSA > 0.2 > 0.2 0.10 LSTc-HSA > 0.2 0.03 GalNAc beta 1-3 Gal-BSA 0.25 Bacteria Burkholder ia (Pseudomonas) cepac ia CELLS Ca lu 3 LNnT 5 .6 LSTc 1 GalNac betal-3 LNnT GalNAc betal-3 Gal betal-4 Glc LNnT-HSA LSTc-HSA Ga lNAc beta l-3 Gal-BSA * The highest concentration tested is 10-15 M of monovalent igosaccharides and 0.2-0.25 M olyosaccharides, for which the molar concentration of carbohydrates is provided. Example 7 10 mL of an isotonic pharmaceutical composition comprising 500 mg of NeuAcalfa2-6-Galbetal-4-61cNAcbeta 1-3-Ga lbeta 1-4 -Glc, 100 mL of sterile water, and 10 mL of propylene glycol is administered to a human patient who has been diagnosed with pneumonia, in the form of an aerosol. The treatment is continued three times a day, at intervals of 8 hours, until the elimination of the bacterial infection. For example, 8 drops of a pharmaceutical composition comprising 1000 mg of NeuAlafa2 ~ 6-Ga lbeta 1-4-GlcNAcbeta 1-3-Ga lbet 1-4-Glc and 100 L of 1,3-butanediol is administered to the pasopharynx of a human patient who has been diagnosed with otitis media, in the form of drops or nasal spray. The treatment is continued twice a day, at intervals of 8 hours, until the elimination of the bacterial infection. Example 9 5 drops of an ophthalmic solution comprising 800 mg of NeuAca lfa2-6-Ga lbeta 1-4-GlcNAcbet 1-3-Ga lbeta 1-4-Glc and 100 mL of an isotonic saline solution are administered to the eye of a patient. human patient who has been diagnosed with conjunctivitis, in the form of eye drops. The treatment is continued 4 times a day, at six-hour intervals, until the elimination of the bacterial infection. Example 10 10 L of an isotonic pharmaceutical composition comprising 500 mg of GalNACbetal-3 ~ Galbetal-4 ~ GlcNAcbetal-3-Galbetal-4-Glc, 100 mL of sterile water, and 10 L of propylene glycol are administered to a human patient at which has been diagnosed with pneumonia, in the form of an aerosol. The treatment is continued three times a day, at intervals of 8 hours, until the elimination of the bacterial infection. EXAMPLE 11 10 mL of an isotonic pharmaceutical composition comprising 500 mg of NeuAcalpha2-3-Galbetal-4-GlcNAcbetal-4-6 lbetal-4-Glc, 100 ml. of sterile water, and 10 mL of propylene glycol are administered to a human patient who has been diagnosed with pneumonia, in the form of an aerosol. The treatment is continued three times a day, at intervals of 8 hours, until the elimination of the bacterial infection. Example 12 10 mL of an isotonic pharmaceutical composition comprising 200 mg of NeuAcal fa.2-6-Galbetal-4-GlcNAcbetal ~ 3 ~ Galbetal-4-Glc-HSA, at a ratio between oligosaccharide and prat of 20: 1, 100 mL of sterile water, and 10 mL of propylene glycol are administered to a human patient who has been diagnosed with pneumonia, in the form of an aerosol. The treatment is continued twice a day, at 12-hour intervals, until the elimination of the bacterial infection. * * * * * * * And indeed, numerous modifications and variations of the present invention can be made based on the above teachings. Accordingly, it is understood that within the scope of the appended claims, the invention may be practiced in a manner other than that specifically described herein.

Claims (11)

1. CLAIMS 1. A method to inhibit coloni. ion p > • A selected battery within the group that onsis or S. piitumonioni, H.? nf l? enzae, H. pa r a i nf luen ^ ae, Bu Mioltlsp. (Psei'domon a > cepac la y utia mix of a, by administration, in an amount effective to inhibit the binding, of the compound the formula I, where 1 R 1 is H, 1-beta-1) Ga 1 ac-, S03B (where B is H or a cation) or b¡ r > an A io ial ico of Formula II: where R6, R7, PT and PIO are each independently H, C1-C6 aolo, lactyl, C1-C6 alkyl, sulfate, phosphate, anhydrous, a sialic acid of formula II, (alpha-l) Was, (beta-1) ) 63c or (beta-l) Gal; R9 is NH-C1-C6 acyl, glycol, amide, amine or hydrogel;
2. A is H or an > .a? ón; R? it is H or (alpha 3) It was; P3 and P4 are either Lino i ndep nd len • "• • • OH or NHA, P5 is H, S03B (where B is H or a cation) or a sialic acid of formula II in accordance with defined above, and Y is a chemical bond or a linking group, 2 is H or a lens support, m is 0 or 1; yps a whole n''uñer of 1 to 1, OO. The method of rei indication 1, where said patient is infected with bacteria sel > -j? _, The ada: - within the ginp that c fis L ste e 5. putei? M >, nie, H Influenza, H. pa ra i nf lueurra, Burfchol depa (Pneudo? i? ona:?) > "eμ3c? - um mez de ll s.
3. 3. The method of claim 2, wherein said patient has bronchitis.
4. 4. The method of claim 2, wherein said patient has pneumonia.
5. 5. The method of claim 1, wherein said patient has otitis media.
6. 6. The method of claim 1, wherein said compound of Formula I is selected from the group consisting of NeuAc 1 fa2-6-Ga lb t 1-4-GlcNAc beta 3 -3-Ga 1 be * 3 -4 -Gl, NeuAca 1 fa? -3-Ga 1 beta 3 -4-GlcNAcbet 1-3-Ga lbet 1 -4-G1, Ga 1 be ta 1 - 4-G 1 NA be ta 3 -3- Sa 1be ta 1 -4- «l, Ne < iAc., 1 fa2--6- Ga lbeta 1-1 -G IcNA be 1 - -Ga 1 bta 1 -4-G1, NeuAca 1 fa -6-Ga Ib 3 -4- íFu a 1 f 3 - 3) GlcNAcbe ugly 1 - 3- Ga ba 1 - 4-61, NeuAc at 1 f - - (Ga 3 NAcbeta 1-3) G beta 1- 4-Gl NAe b ta 3 -3- Ga lbetal-4-Glc, NeuAcal fa -6- (G l Acbet 1-) Ga lbeta 1 -4- (Fuc lf33-3) GlcNAcbetal-3-Galbetal ~ 4-G3, NeuAca 1 fa2-6-Galbetal-4-GlcNAc, NeuAcal f a2-6 -6albetal ~ 4- (went to fal-3) 61cNAc, NeuA-_ to fa2-6- (Ga INAcbeta l ~ 3) 6a Ibeta 3 -4-GlcNAc, NeuAc lfa2- 6- (G INAc betal -3) 6albe fc 1-4- (Fucal fal-3) GlcNAc, GalNAcbetat-3-Ga lbetal-4-61c Acbet-31-3-Ga lbeta 1-4-Glc, Ga 1 Acbeta 3 -3-Ga 3 beta 3 -4 - GA, Od 1 acbet 1-3-Ga 1 be a 1 -4-G 1 c, NeuAca 1 f 2 ~ 3-Ga 1 bet a 1 -4-G1 c NAc, Nei iAc alf a2-6-Ga 1 bet a 1 -4-Glr NAc beta 1-3- s 1 b ta 3 -4-G3 NAc, NeuA .. = t 1 f al > -3 -Gal be a 1-4-Gl c NAcbeta 3 -3-Ga 1 ba 3 -4- Gl.-NAc, Ga Ibe la 3 -4 - G1 cNAcbe a 1-3-Ga lbet 1-4- GlcNA, NeuA il f. =. 2-6-6: 3 lbe 3-4- (Fucal f l-3) GlcNA betal-3-G lbetal-4-GlcNAc, NeuAc lfa2-6- (G INAcbe 1- ) Ga lbe to 1-4-GlcNAc beta 1 -3-G Ibeta t -4-GlcNA, NeuAcalfa2-6- (G =? 1 NAcbeta l-3) Ga lbeta 1-4- (Fucal fal-3) 61cNAcb tl -3-Ga lbeta 1-4-Gl NAc, Ga INAcbeta 1-3-G lbeta 3 -4-G IcNAcbet l -3-G lbet 1-4-GlcNAc, and Ga 1 NAcbeta 1-3-G 1 betal - 4-GlcNAc and a mixture thereof.
7. 7. The method of claim 1, wherein said compound of formula I is of the formula where Y is a chemical bond or a linking group; Z is H or a support or 11 va lens; and p is an integer from 1 to 100.
8. 8. The method of claim 7, wherein Y is a chemical bond, Z is H and p is 1.
9. 9. A pharmaceutical composition for inhibiting colonization by bacteria selected from the group consisting of S. pneu oniiie, H. inf. luenrae, H.? .- < r -3 i nf lu n. i-_, EurUioldep a (P ^ eudomon s) cepacia, and an in ^ .cl. d 1 r¡ - same, by the addition of an effective combination to inhibit the binding of the compound of form I, where R3 e *. H, (beta-3) Ga 3 Nac-, S03B (where B is H or a cation) or a sialic acid of Formula II; where P¿ > , P7, RR \ P10 - are each independently H, C1-C6 acyl, lictyl, C1-C6 alkyl, = > phosphate, phosphate, anhydrous, or acid if Mico of formula II, ia 3 f a -3) Fuc, (boot-l) Glc or (beta-3) Gal; P9 is C1-C6 NH-allyl, glycol and lame, to "one or else"; and A is H or a cation; R2 is H or (alpha-l) Fuc; P3 and P4 are each independently OH or NHA; P5 is H, 503B (where B is H or a cation) or a sialic acid of formula II according to that defined above; and Y is a chemical bond or a linking group; Z is H or a support mu 111 va 1 entity; m is O or 1; and p is an integer from 1 to 1,000. where when R5 is H, Rl is not H and when Pl is a sialic acid, R2 is not (alpha-) was.
10. 10. The composition of claim 3, wherein said compound of formula I is selected from the group consisting of NeuAc lfa2-6-6a lbet 1-4-Glc NAcbeta 1-3-G lbeta 1-4-Glc, NeuAca lfa2-3-G lbeta 1-4-GIcNAcbeta1-3-Ga lbet 1-4-Glc, NeuAc 1 fa2 ~ 6-Ga lbeta 1-4- (Fuca 1 fa 1-3) GlcNAcbeta 3 -3-Ga 1beta 1-4-Glc, NeuAcalfa2-6- (GalNAcbetal-3) 6albeta3-4-61cNAcbeta3-3- 6a 3 beta 1 -Glc, NeuAc 1 f a2-6- (G 1 NAc bet to 3 -3) G lbe to 1-4- (Fuealf al-3) GlcNA beta l -3-Ga Ibe 31-4- 6le, NeuA 1 f -6-Galbetal-4-G3 NA »-, NeuAca 3 f a2 -6-6a lbe la 1-4- (Fuca 3 f l-3) 61cNAc, NeuAc a 1 fa2 ~ 6- (G i INA üet 11-3) Ga ltata 1 -4-Gl.-NA, NeuAc3lfa2-6- (G INAcbeta 3 -3) G Ib 1 -4- (F? ea3 fal-3) 61cNA, Ga INAcbeta 1-3 -Ga ltabe 1-4-GlcNAcb tl -3-G 1b tal -4 ~ G3c, Ga 3 NAcbet l-3-6 lbe to 1-4-GlcNAc, Ga Nacbe a 1-3-G lbet 1-4-Glc , NeuAc lfa2-3-Galbetal-4-GlcNAc, NeuAcalf 32-6-Ga 1beta 1-4-GlcNAcbetal -3-Ga Ibeta 1-4-61 cNAc, NeuAc l fa2-3-6a 1 bet 1-4-G3cNAcbetal -3-6albet l-4-GlcNAc, G lbet l-4-GlcNAcb t 3 -3-Ga lbeta 1-4-GlcNAc, NeuAcal fa? - 6-Ga lbeta 1-4- (Fu. Alfal-3) GlcNAcbetal ~ 3-6a 3 beta 1-4-GlcNA, NeuAc 33 fa2-6- (6a INAcbeta 1-3 G lbet 1-4-GlcNAcbet 1 - -G 1bet l -4- Gl * NAc, NeuAc Hlfa2-6- (Ga INA ba 1-3) Ga lbe ta 1-4- Fu l fa -3) GlcNAcbetal-3-Galbet33-4-GlcNAc, G 1 NAcbe 31-3-Ba lbeta 1-4-GlcNAcbetal-3-Galbetal-4-GlcNAc, G INAcbeta 1-3-Ga 1-4-GlcNAc, and a mixture thereof.
11. 11. The pharmaceutical composition of claim 9, wherein said composition is in a form suitable for administration as an aerosol. BF ^ ÜMEN DL "THE INVENTION l.-t present inve ci s refers to my m all n ^ r the treaty and infei nas r'fsp i t a lonas p u oci". for a-bacteria is l *. ? opad3 inside dol gr »? po that > _? > ns? ste of S. pneu umae, H. influencie, H. par3 i nf luencae, Bu i 1 holder i á (Pseudomonas ce? a?) and a mixture thereof, by administering a quantity effective inhibitor of the compound of the formula (I), wherein R1 is H, (beta-1) G INAc-, S03B (where B is a H or a cation) or a sialic acid of the formula (II), wherein P6, R7 , PE) and PIO are each independently H, C 1 -C 6 acyl, lactyl, C 1 -C 6 alkyl, sulfate, phosphate, anhydrous, > _ > sialic gone of formula til'-, ialfa-1) F? ._, ibeta-3) Glc or bi n (t? eta-1) Gzt 1; Rc is NH-acyl C1-C6, g3 icol i 1 = t gone, to irio or hidrónlo; and A is H or a cation; P2 is H or (31 f - 1) ruc-; R3 and P4 are each independently OH or NHA; P5 is H, S03B (where B is H or a cation) or a sialic acid of the formula (II) according to the above defined; and Y is a chemical bond or a linking group; 2 is H or bi n a multi-valent support; m is 0 or 1; and p is an integer from 1 to 1000; and a pharmaceutical composition containing it.