WO2011083291A1

WO2011083291A1 - Combinations comprising an ant i -inflammatory agent and/or an antibacterial agent and a glycosylamine and their use in medicine

Info

Publication number: WO2011083291A1
Application number: PCT/GB2010/051109
Authority: WO
Inventors: Julian Manuel Galvez; Michael Peter Seed; Ivan Maurice Roitt; Michael Burnet
Original assignee: Julian Manuel Galvez; Michael Peter Seed; Ivan Maurice Roitt; Michael Burnet
Priority date: 2010-01-07
Filing date: 2010-07-05
Publication date: 2011-07-14
Also published as: GB201000196D0

Abstract

The present invention relates to pharmaceutical compositions and kits comprising an anti-inflammatory and/or an antibacterial agent, and a glycosylamine such as β,β-di-glucosylamine. Preferably the anti-inflammatory is a COX inhibitor such as aspirin, ibuprofen, naproxen or a selective COX-2 inhibitor. Alternately, instead or in addition to the glycosylamine, the compositions or kits may comprise precursor(s) of the glycosylamine such as glucose and/ or ammonium salts. The compositions and kits are suitable for use in the treatment or prevention of inflammation, pain, fever, cancer or cardiovascular disorders, and for use in the treatment of wounds. The present invention also relates to uses of glycosylamines or precursors thereof to treat or prevent side effects associated with the administration of anti-inflammatories and/or antibacterial agents.

Description

COMBINATIONS COMPRISING AN ANT I -INFLAMMATORY AGENT AND/OR

AN ANTIBACTERIAL AGENT AND A GLYCOSYLAMINE AND THEIR USE IN MEDICINE

Technical field

The present invention relates to pharmaceutical compositions and kits comprising an anti-inflammatory and/or an antibacterial agent, and a glycosylamine such as β,β- di-glucosylamine. Preferably the anti-inflammatory is a COX inhibitor such as aspirin, ibuprofen, naproxen or a selective COX-2 inhibitor. Alternately, instead or in addition to the glycosylamine, the compositions or kits may comprise precursor(s) of the glycosylamine such as glucose and/or ammonium salts. The compositions and kits are suitable for use in the treatment or prevention of inflammation, pain, fever, cancer or cardiovascular disorders, and for use in the treatment of wounds. The present invention also relates to uses of glycosylamines or precursors thereof to treat or prevent side effects associated with the administration of anti-inflammatories and/or antibacterial agents.

Background of the invention

The use of β,β-di-glucosylamine to treat adverse inflammatory reactions is known for instance from US 6,770,635. As an alternative, the same patent also suggests the use of enteric-coated glucose, administered to the organism in the presence of ammonia at a pH≥ 7, allowing β,β-di-glucosylamine to be generated in-situ.

US 6,770,635 suggests combining this treatment with the use of other medicaments. More specifically it suggests that the use of such treatments will indirectly increase the efficacy of other compounds treating diseases that are not considered as being of the inflammatory type. Combinations with for example antifungal compounds, analgesics and antacids are speculated upon, but the efficacy of such combinations is not demonstrated. Summary of the invention

However, contrary to this prior art teaching it has now been discovered that the use of glycosylamines or precursors thereof can also substantially enhance the activity and reduce the side effects of other compounds used to treat inflammatory diseases, such as COX inhibitors. It has further now been discovered that glycosylamines and precursors thereof are also effective at enhancing the activity and reducing the side effects of antibacterial agents such as antibiotics. The present invention is based upon these findings.

Accordingly, a first aspect of the present invention relates to a pharmaceutical composition or kit comprising:

(a) an anti-inflammatory or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof; and

(b) a glycosylamine or one or more precursors thereof, or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate of said glycosylamine or precursor (s).

As used herein, a pharmaceutical 'composition' refers to a pharmaceutical wherein the components are present as a union, i.e. in a single dosage form, for example as a single tablet or powder containing the components. In contrast, in a pharmaceutical 'kit' the components of that kit are not present as a single union, but are in separate dosage forms for administration simultaneously, separately, sequentially or at intervals to one and the same human or animal body.

Preferably the first aspect of the present invention relates to a pharmaceutical composition.

Preferably the anti-inflammatory is a COX inhibitor. As used herein, a 'COX inhibitor' refers to an inhibitor of cyclooxygenase. In one embodiment of the first aspect of the present invention, the COX inhibitor is a non-steroidal antiinflammatory drug (NSAID). Preferably said NSAID is selected from: (a) an aminoarylcarboxylic acid derivative such as enfenamic acid, etofenamate, flufenamic acid, isonixin, meclofenamic acid, mefenamic acid, niflumic acid, talniflumate, terofenamate or tolfenamic acid;

(b) an ai lacetic acid derivative such as aceclofenac, acemetacin, alclofenac, amfenac, amtolmetin guacil, bromfenac, bufexamac, diclofenac, etodolac, felbinac, fenclozic acid, fentiazac, glucametacin, ibufenac, indomethacin, isoxepac, lonazolac, metiazinic acid, mofezolac, nepafenac, oxametacine, proglumetacin, sulindac, tiaramide, tolmetin, tropesin or zomepirac;

(c) an aiylbutyric acid derivative such as bumadizon, butibufen, butixirate or fenbufen;

(d) an arylcarboxylic acid derivative such as ketorolac or tinoridine;

(e) an arylpropionic acid derivative such as alminoprofen, bermoprofen, carprofen, fenoprofen, flunoxaprofen, flurbiprofen, ibuprofen, ibuproxam, ketoprofen, loxoprofen, naproxen, oxaprozin, piketoprofen, pranoprofen, suprofen, tiaprofenic acid, ximoprofen or zaltoprofen;

(f) a pyrazole derivative such as difenamizole or epirizole;

(g) a pyrazolone derivative such as apazone, feprazone, mofebutazone, morazone, oxyphenbutazone, phenylbutazone, pipebuzone, propyphenazone, ramiphenazone or suxibuzone;

(h) a salicylic acid derivative such as acetaminosalol, aspirin, balsalazide, benorylate, diflunisal, fendosal, gentisic acid, glycol salicylate, imidazole salicylate, lysine acetylsalicylate, mesalamine, morpholine salicylate, 1-napthyl salicylate, olsalazine, parsalmide, phenyl acetylsahcylate, phenyl salicylate, salicylamide O- acetic acid, salicylsulphuric acid, salsalate, salicylic acid or sulfasalazine;

(i) a thiazinecarboxamide derivative such as ampiroxicam, lornoxicam, meloxicam, piroxicam or tenoxicam;

(j) a selective COX-2 inhibitor such as celecoxib, etoricoxib, lumiracoxib, parecoxib, rofecoxib or valdecoxib; or

(k) another NSAID such as ε-acetamidocaproic acid, S- adenosylmethionine, ajulemic acid, 3-amino-4-hydroxybutyric acid, bendazac, benzydamine, oc-bisabolol, bucolome, difenpiramide, ditazol, emorfazone, fepradinol, guaiazulene, lexipafant, licofelone, nabumetone, nimesulide, oxaceprol, perisoxal, proquazone, superoxide dismutase or tenidap. In a preferred embodiment, said NSAID is a salicylic acid derivative such as aspirin. Where the NSAID is a salicylic acid derivative, a typical unit dosage size is lOmg to 2000mg, more preferably 50mg to 1500mg, most preferably 75mg to 900mg.

In another preferred embodiment, said NSAID is an arylpropionic acid derivative such as ibuprofen or naproxen. Where the NSAID is an arylpropionic acid derivative, a typical unit dosage size is 50mg to 2000mg, more preferably lOOmg to 1500mg, most preferably 200mg to 600mg.

In yet another preferred embodiment, said NSAID is a selective COX-2 inhibitor. Where the NSAID is a selective COX-2 inhibitor, a typical unit dosage size is 5mg to lOOOmg, more preferably lOmg to 500mg, most preferably 20mg to 250mg. In another embodiment, the anti-inflammatory is a steroid. Preferably the steroid is a corticosteroid such as 21-acetoxypregnenolone, fludrocortisone, fluticasone furoate, fluticasone propionate, alclometasone, algestone, amcinonide, beclomethasone, betamethasone, budesonide, chloroprednisone, ciclesonide, clobestasol, clobetasone, clocortolone, cloprednol, cortisone, cortivazol, deflazacort, desonide, desoximetasone, dexamethasone, diflorasone, diflucortolone, difluprednate, enoxolone, etiprednol dicloacetate, fluazacort, flucloronide, flumethasone, flunisolide, fluocinolone acetonide, fluocinonide, fluocortin butyl, fluocortolone, fluorometholone, fluperolone acetate, fluprednidene acetate, fluprednisolone, flurandrenolide, fluticasone propionate, formocortal, halcinonide, halobetasol propionate, halometasone, halopredone acetate, hydrocortamate, hydrocortisone, loteprednol etabonate, mazipredone, medrysone, meprednisone, methylprednisolone, mometasone furoate, paramethasone, prednicarbate, prednisolone, prednisone, prednival, prednylidene, rimexolone, tixocortol, triamcinolone, triamcinolone acetonide, triamcinolone benetonide or triamcinolone hexacetonide.

Most preferably, the steroid is selected from hydrocortisone, betamethasone, cortisone, deflazacort, dexamethasone, methylprednisolone, prednisolone, triamcinolone, fludrocortisone, beclomethasone, budesonide, ciclesonide, fluticasone furoate, mometasone furoate, flunisolide, flumethasone, fluorometholone or loteprednol etabonate. In yet another embodiment, the anti-inflammatory is an anti-interleukin-6 agent such as tocilizumab, anti-IL-6 chimeric monoclonal antibody, ALD518 or CNTO 136. Preferably the anti-interleukin-6 agent is tocilizumab.

In a further embodiment, the anti-inflammatory is a sulphated saccharide such as those disclosed in WO 2008/152423, which is hereby incorporated herein by reference in its entirety. Preferably the sulphated saccharide is sucrose octasulphate or sucralfate.

A second aspect of the present invention relates to a pharmaceutical composition or kit comprising:

(a) an antibacterial agent or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof; and

(b) a glycosylamine or one or more precursors thereof, or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate of said glycosylamine or precursor(s).

Preferably the second aspect of the present invention relates to a pharmaceutical composition. In one embodiment, the antibacterial agent is an antibiotic. The antibiotic may be selected from:

(a) aminoglycosides such as amikacin, arbekacin, bambermycins, butirosin, dibekacin, dihydrostreptomycin, fortimicins, gentamicin, isepamicin, kanamycin, micronomicin, neomycin, netilmicin, paromomycin, ribostamycin, sisomicin, spectinomycin, streptomycin or tobramycin;

(b) amphenicols such as azidamfenicol, chloramphenicol or thiamphenicol; ansamycins such as rifamide, rifampin, rifamycin SV, rifapentine or β-lactams including carbacephems such as loracarbef; carbapenems such as biapenem, doripenem, ertapenem, imipenem, meropenem or panipenem; cephalosporins such as cefaclor, cefadroxil, cefamandole, cefatrizine, cefazedone, cefazolin, cefcapene pivoxil, cefdinir, cefditoren, cefepime, cefetamet, cefixime, cefmenoxime, cefodizime, cefonicid, cefoperazone, ceforanide, cefoselis, cefotaxime, cefotiam, cefozopran, cefpimizole, cefpiramide, cefpirome, cefpodoxime proxetil, cefprozil, cefroxadine, cefsulodin, ceftazidime, cefteram, ceftezole, ceftibuten, ceftizoxime, ceftobiprole medocaril, ceftriaxone, cefuroxime, cefuzonam, cephacetrile sodium, cephalexin, cephaloglycin, cephaloridine, cephalosporin C, cephalothin, cephapirin sodium, cephradine or pivcefalexin; cephamycins such as cefbuperazone, cefmetazole, cefminox, cefotetan or cefoxitin; monobactams such as aztreonam or carumonam; oxacephems such as flomoxef or moxalactam; penems such as faropenem or ritipenem; and penicillins such as amdinocillin, amdinocillin pivoxil, amoxicillin, ampicillin, apalcillin, aspoxicillin, azidocilhn, azlocilhn, bacampicillin, carbenicillin, carindacillin, clometocillin, cloxacillin, cyclacillin, dicloxacilhn, epicillin, fenbenicilhn, floxacillin, hetacillin, lenampicillin, metampicilhn, methicillin sodium, mezlocillin, nafcillin, oxacillin, penamecillin, penethamate hydriodide, penicilUn G, penicillin G benzathine, penicillin G procaine, penicillin N, penicillin O, penicillin V, phenethiciUin potassium, piperacillin, pivampicillin, propicillin, quinacillin, sulbenicillin, sultamicillin, talampicillin, temociUin or ticarcillin;

(e) hncosamides such as clindamycin or lincomycin;

(f) macrolides such as azithromycin, cethromycin, clarithromycin, dirithromycin, erythromycin, erythromycin ethylsuccinate, erythromycin acistrate, erythromycin estolate, erythromycin glucoheptonate, erythromycin lactobionate, erythromycin propionate, erythromycin stearate, josamycin, leucomycins, midecamycins, miokamycin, oleandomycin, primycin, rokitamycin, rosaramicin, roxithromycin, spiramycin, telithiOmycin or troleandomycin;

(g) polypeptides such as amphomycin, bacitracin, bacitracin zinc, capreomycin, colistin, dalbavancin, daptomycin, enduracidin, enviomycin, fusafungine, gramicidin (s), gramicidin S, iseganan, oritavancin, polymyxin, quinupiistin, ramoplanin, ristocetin, teicoplanin, telavancin, thiostrepton, tuberactinomycin, tyrocidine, tyrothricin, vancomycin or viomycin;

(h) tetracyclines such as chlortetracycline, clomocycline, demeclocycline, doxycycline, guamecycline, lymecycline, meclocycline, mefhacycline, minocycline, oxytetracycline, pipacycline, rolitetracycline, tetracycline or tigecycline; or

(i) other antibiotics such as cycloserine, dalfopristin, fosfomycin, fusidic acid, mupirocin, pristinamycin or virginiamycin.

Preferably the antibiotic is selected from amikacin, gentamicin, neomycin, tobramycin, cefaclor, cefadroxil, cephalexin, cefixime, cefotaxime, cefpodoxime proxetil, cephradine, ceftazidime, ceftriaxone, cefuroxime, azithromycin, clarithromycin, erythromycin, erythromycin ethylsuccinate, erythromycin stearate, telithromycin, amoxicilhn, ampicillin, floxacillin, penicilUn G, penicillin V, piperacillin, ticarcillin, rifampin, demeclocycline, doxycycline, lymecycline, minocycline, oxytetracycline, tetracycline, aztreonam, chloramphenicol, clindamycin, colistin, daptomycin, doripenem, ertapenem, imipenem, meropenem, quinupiistin, dalfopristin, fusidic acid, teicoplanin, tigecycline or vancomycin.

In another embodiment, the antibacterial agent is a synthetic antibacterial agent. The synthetic antibacterial agent may be selected from:

(a) 2,4-diaminopyrimidines such as brodimoprim, tetroxoprim or trimethoprim;

(b) nitrofurans such as furaltadone, furazolium chloride, nifuratel, nifurfoline, nifurpirinol, nifurtoinol or nitrofurantoin;

(c) oxazolidinones such as linezolid;

(d) quinolones and analogs thereof such as balofloxacin, cinoxacin, ciprofloxacin, clinafloxacin, enoxacin, fleroxacin, flumequine, garenoxacin, gatifloxacin, gemifloxacin, grepafloxacin, levofloxacin, lomefloxacin, miloxacin, moxifloxacin, nadifloxacin, nalidixic acid, norfloxacin, ofloxacin, oxolinic acid, pazufloxacin, pefloxacin, pipemidic acid, piromidic acid, pruhfloxacin, rosoxacin, rufloxacin, sitafloxacin, sparfloxacin, tosufloxacin or trovafloxacin;

(e) sulfonamides such as acetyl sulfamethoxypyrazine, chloramine-B, chloramine-T, dichloramine T, N²-formylsulfisomidine, mafenide, noprylsulfamide, phthalylsulfacetamide, phthalylsulfathiazole, salazosulfadimidine, succinylsulfathiazole, sulfabenzamide, sulfacetamide, sulfachloropyridazine, sulfachrysoidine, sulfacytine, sulfadiazine, sulfadicramide, sulfadoxine, sulfaethidole, sulfaguanidine, sulfaguanole, sulfalene, sulfaloxic acid, sulfamerazine, sulfameter, sulfamethazine, sulfamethizole, sulfamethomidine, sulfamethoxazole, sulfamethoxypyridazine, sulfametrole, sulfamidochiysoidine, sulfamoxole, sulfanilamide, N⁴-sulfanilylsulfanilamide, sulfanilylufea, N-sulfanilyl-3,4-xylamide, sulfaperine, sulfaphenazole, siilfaproxyline, sulfapyrazine, sulfapyridine, sulfathiazole, sulfathiourea, sulfisomidine or sulfisoxazole;

(f) sulfones such as acediasulfone, dapsone, glucosulfone sodium, solasulfone, succisulfone, sulfanilic acid, p-sulfanilylbenzylamine, sulfoxone sodium or thiazolsulfone; or

(g) other synthetic antibacterial agents such as clofoctol, methenamine, metronidazole, nitroxoline, noxythiohn, pexiganan, taurolidine, tinidazole or xibo nol.

Preferably the synthetic antibacterial agent is selected from metronidazole, tinidazole, ciprofloxacin, levofloxacin, ofloxacin, moxifloxacin, nalidixic acid, trimethoprim, sulfamethoxazole, linezolid or noxythiolin.

In yet another embodiment, the antibacterial agent is a leprostatic agent such as clofazimine, dapsone, glucosulfone sodium, hydnocarpic acid, solasulfone, succisulfone or sulfoxone sodium. In a further embodiment, the antibacterial agent is an anti-rickettsial agent such as p-aminobenzoic acid, chloramphenicol or tetracycline.

In another embodiment, the antibacterial agent is a tuberculostatic agent such as p- amino salicylic acid, p-aminosalicylic acid hydrazine, benzoylpas, 5- bromosalicylhydroxamic acid, capreomycin, clofazimine, cyacetacide, cycloserine, dihydrostreptomycin, enviomycin, ethambutol, ethionamide, furonazide, glyconiazide, isoniazid, morphazinamide, opiniazide, phenyl aminosalicylate, protionamide, pyrazinamide, rifabutin, rifalazil, rifampin, rifapentine, salinazid, streptomycin, sulfoniazide, thiacetazone, tuberactinomycin or viomycin.

In yet another embodiment, the antibacterial agent is an antibacterial adjunct. Preferably the antibacterial adjunct is selected from:

(a) β-lactamase inhibitors such as clavulanic acid, sulbactam, sultamicillin or tazobactam;

(b) renal dipeptidase inhibitors such as cilastatin; or

(c) renal protectants such as betamipron.

More preferably, the antibacterial adjunct is selected from clavulanic acid, tazobactam or cilastatin.

Preferably any pharmaceutical composition or kit containing an anti-inflammatory or antibacterial agent (including those containing a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof) contains a single unit dosage of said antiinflammatory or antibacterial agent or a fraction of a single unit dosage such as 1 /2, 1/3 or 1 /4. Most preferably any pharmaceutical composition or kit containing an anti-inflammatory or antibacterial agent contains a single unit dosage of said anti- inflammatory or antibacterial agent.

Preferably any pharmaceutical composition or kit containing a glycosylamine or one or more precursors thereof (including those containing a pharmaceutically acceptable tautomer, salt, prodrug or hydrate of said glycosylamine or precursor(s)) contains a single unit dosage of said glycosylamine or one or more precursors thereof, or a fraction of a single unit dosage such as 1 /2, 1/3 or 1/4. Most preferably any pharmaceutical composition or kit containing a glycosylamine or one or more precursors thereof contains a single unit dosage of said glycosylamine or one or more precursors thereof.

In one embodiment of the present invention, the glycosylamine comprises at least one monosaccharide subunit comprising a glycosidic -NR₂ group, a glycosidic -NR₃ ⁺ group, a directly bonded =NR group, or a directly bonded =NR₂ ⁺ group; wherein each R is independently hydrogen, a further monosaccharide subunit, or a hydrocarbyl group, or two or three R groups and the nitrogen atom to which they are attached, together form a further monosaccharide subunit or a cychc hydrocarbyl group;

wherein each monosaccharide subunit independently is optionally substituted and/ or optionally modified; and

wherein each hydrocarbyl group independently is a substituted or unsubstituted, straight-chain, branched or cyclic alkyl, alkenyl, alkynyl, acyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, alkylaryl, alkenylaryl or alkynylaryl group which optionally includes one or more heteroatoms in its carbon skeleton.

Preferably in such an embodiment:

(a) one R group is not hydrogen; and/ or

(b) two R groups are not hydrogen; and/ or

(c) one R group is a monosaccharide subunit and one R group is a hydrocarbyl group; and/ or

(d) one R group is a monosaccharide subunit and one R group is hydrogen; and/ or

(e) one R group is a hydrocarbyl group and one R group is hydrogen; and/ or

(f) two R groups are independently monosaccharide subunits; and/or

(g) two R groups are independently hydrocarbyl groups; and/ or

(h) one or two R groups are independently hydrogen, or an alkyl, acyl or alkoxycarbonyl group; and/or

(i) one or two R groups are independently hydrogen, or a C C₆ alkyl, C₂-C₆ acyl, C₂-C₆ halo-acyl, or C_j_₂₀ alkoxycarbonyl group; and/ or

(j) one or two R groups are independently a methyl, ethyl, acetyl, trifluoroacetyl, Boc, Fmoc, or Zervas group; and/ or

(k) all R groups are hydrogen; and/or

(1) one R group is a hydrocarbyl group or a monosaccharide subunit and one R group is an acyl group. The glycosylamine may comprise a sequence of at least two monosaccharide subunits directly linked by a glycosidic -NR- group, a glycosidic -NR₂ ⁺- group, a directly bonded =N- group, or a directly bonded =NR⁺- group. Preferably they are directly linked by a glycosidic -NR- group or a glycosidic -NR₂ ⁺- group; alternatively they may be directly linked by a glycosidic -NR- group or a directly bonded =N- group.

For the purposes of the present invention, when two monosaccharide subunits are 'directly linked' by a glycosidic -NR- group, a glycosidic -NR₂ ⁺- group, a directly bonded =N- group, or a directly bonded =NR⁺- group, the group is directly bonded to both monosaccharide subunits without any intervening atoms being present, such that the compound comprising the two monosaccharide subunits is or comprises a poly- or oligosaccharide. The glycosidic -NR- group or the glycosidic -NR₂ ⁺- group may be linked to one or both of the monosaccharide subunits by a glycosidic bond. The directly bonded =N- group or the directly bonded =NR⁺- group may be linked to one or neither of the monosaccharide subunits by a glycosidic bond.

The glycosylamine may also comprise at least one monosaccharide subunit comprising a glycosidic -NR₂ group or a directly bonded =NR group. In an alternative embodiment, the glycosylamine comprises at least one monosaccharide subunit comprising a glycosidic -NR₂ group or a glycosidic -NR₃ ⁺ group.

In one embodiment of the present invention, the at least one monosaccharide subunit is not substituted with an -OR group, wherein R is any group comprising a further monosaccharide subunit.

In another embodiment, the glycosylamine may contain 1-100, 1-20, 1-12, 2-10, 2-8, 2-6 or 2-4 monosaccharide subunits. Alternatively, the glycosylamine may comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more monosaccharide subunits. The glycosylamine may contain 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 monosaccharide subunits. The glycosylamine may comprise a sequence of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more monosaccharide subunits. It is preferred that, in total, including any further monosaccharide subunits, the glycosylamines used in the present invention contain one to twelve monosaccharide subunits, preferably one to eight monosaccharide subunits, preferably one to six monosaccharide subunits, preferably two to four monosaccharide subunits, preferably two to three monosaccharide subunits. Alternatively, the glycosylamines may contain, in total, including any further monosaccharide subunits, one monosaccharide subunit, or two monosaccharide subunits, or three monosaccharide subunits, or four monosaccharide subunits, or five monosaccharide subunits, or six monosaccharide subunits, or seven monosaccharide subunits, or eight monosaccharide subunits, or nine monosaccharide subunits, or ten monosaccharide subunits, or eleven monosaccharide subunits, or twelve monosaccharide subunits.

In one embodiment, all the monosaccharide subunits are independently aldosyl or ketosyl monosaccharides. Preferably 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or all monosaccharide subunits are independently triosyl, tetrosyl, pentosyl, hexosyl, heptosyl, octosyl or nonosyl monosaccharides. More preferably 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or all monosaccharide subunits are independently glycerosyl, erythrosyl, threosyl, ribosyl, arabinosyl, xylosyl, lyxosyl, allosyl, altrosyl, glucosyl, mannosyl, gulosyl, idosyl, galactosyl, talosyl, rhamnosyl or fucosyl monosaccharides.

In a preferred embodiment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or all monosaccharide subunits are independently tetrosyl monosaccharides or higher, and the ring of those monosaccharides is furanosyl. In another preferred embodiment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or all monosaccharide subunits are independently pentosyl monosaccharides or higher, and the ring of those monosaccharides is pyranosyl.

For the purposes of the present invention, a 'saccharide' is any compound comprising at least one monosaccharide subunit, optionally substituted and/ or optionally modified. Thus, by this definition, a glycosylamine of the present invention is a saccharide. A saccharide may be a mono-, oligo- or polysaccharide. An 'oligosaccharide' may comprise between 2 and 10 monosaccharide subunits and may therefore be a disaccharide, trisaccharide, tetrasaccharide, pentasaccharide, hexasaccharide, heptasaccharide, octasaccharide, nonasacchaiide, or decasaccharide. A 'polysaccharide' may comprise 11 or more monosaccharide subunits.

For the purposes of the present invention, the term 'monosaccharide subunit' refers to a monosaccharide optionally substituted and/or optionally modified, which may or may not be part of a compound comprising more than one monosaccharide subunit. Thus, for the avoidance of doubt, it is noted that the present invention covers compounds comprising just one monosaccharide subunit, such as monosaccharides.

For the purposes of the present invention, where a compound 'contains x monosaccharide subunits', this means that the compound has x monosaccharide subunits and no more, unless it is explicitly mentioned that the compound contains or comprises further monosaccharide subunits. In contrast, where a compound 'comprises x monosaccharide subunits', this means that the compound has x or more monosaccharide subunits.

The single bond between an anomeric carbon of a monosaccharide subunit and a substituent is called a glycosidic bond. A glycosidic group is linked to the anomeric carbon of a monosaccharide subunit by a glycosidic bond. One distinguishes between a- and β-glycosidic bonds depending on whether the participating anomeric carbon is in the oc or β configuration. In the standard Haworth way of drawing monosaccharide subunits, an oc-glycosidic bond of a D-monosaccharide subunit emanates below the plane of the monosaccharide subunit and a β-glycosidic bond emanates above that plane, and vice versa for an L-monosaccharide subunit.

For the purposes of the present invention, a 'glycosylamine' is any compound comprising at least one monosaccharide subunit with a glycosidic amine group. A 'glucosylamine' is any compound comprising at least one glucose subunit with a glycosidic amine group. A 'β,β-di-glucosylamine' is any compound comprising at least two glucose subunits linked by a β,β-glycosidic amine group. A β,β-glycosidic amine group is linked to the anomeric carbons of two monosaccharide subunits, with both glycosidic bonds being β-glycosidic bonds.

All monosaccharide subunits are independently ring-closed or open-chain or a mixture of ring-closed and open-chain. Ring-closed and open-chain monosaccharide subunits are tautomers of each other, which exist in their cyclic and acyclic forms respectively (with respect to the portion of the molecule referred to). For example, in the equilibrium below, A is the open-chain tautomer and B is the ring-closed tautomer:

B

Thus, in the context of the present invention, it is understood that any substituent that contains a hydrogen atom of moderate acidity (e.g. a hydroxyl, amino or thiol group proton) may interact with the π-bond illustrated so as to establish the above equilibrium. A 'hydrogen atom of moderate acidity' is defined as one with an approximate pK_a (relative to water) of less than 40, preferably less than 30, preferably less than 25, preferably less than 20. It is also understood that in some cases it is not possible to establish the above equilibrium due to a lack of a suitable hydrogen atom and the relevant portion of the molecule is effectively 'locked' in its open-chain form. In other cases, the relevant portion of the molecule will exist predominantly in its ring-closed form with little or none of the open-chain form being detectable. It is also to be understood that more than one equilibrium may be established within a given portion of the molecule, for example, the scenario below may be established, wherein the molecule exists in two ring-closed forms C and E, and one open-chain form D.

A pyranosyl monosaccharide subunit is a cycHc saccharide with a six-membered ring. Pyranosyl monosaccharide F shown below has been marked with substituent X in the 2-position relative to the anomeric carbon of the pyranosyl subunit:

As used herein, where it is specified that a first group is located a to a second group, this means that the first group is attached to a carbon atom one bond removed from the carbon atom to which the second group is attached. Similarly, where it is specified that a first group is located β to a second group, this means that the first group is attached to a carbon atom two bonds removed from the carbon atom to which the second group is attached, and so on for groups located y, δ etc. Where it is specified that a first group is located ω to a second group, this means that the first group is attached to the furthest carbon atom removed, along a continuous chain of carbon atoms, from the carbon atom to which the second group is attached. Formula G below has been marked with substituents X in the -, β-, γ-, δ- and ω-positions relative to the group Y:

For the purposes of the present invention, the term 'directly bonded' used in relation to a monosaccharide subunit comprising a group, means that the group is bonded to the carbon backbone of the monosaccharide subunit without any intervening atoms being present.

Each monosaccharide subunit independently may be substituted and/or modified.

Formula H below has been marked with substituents X in the 2-, 3-, 4- and 6- positions relative to the anomeric carbon of the pyranosyl subunit:

In a substituted monosaccharide subunit:

(a) independently one or more of the hydroxyl groups of the monosaccharide subunit is replaced with -H, -F, -CI, -Br, -I, -CF₃, -CCL, -CBr₃, -CI₃, -SH, -NH₂, -N₃, -NH=NH₂, -CN, -N0₂, -COOH, -R^a-0-R^b, -R^a-S-R^b, -R^a-SO-R^b, -R^a-S0₂-R^b, -R^a-S0₂-OR^b, -RO-S0₂-R^b, -R^a-S0₂-N(R )₂, -R^a-NR^b-S0₂-R^b, -RO-S0₂-OR^b, -RO-S0₂-N(R^b)₂, -R^a-NR^b-S0₂-OR^b, -R^a-NR -S0₂-N(R^b)₂, -R^a-N(R^b)₂, -R^a-N(R^b)₃ ⁺, -R^a-B(R^b)₂, -R^a-P(R )₂, -R^a-PO(R^b)₂, -R^a-Si(R^b)₃, -R^a-CO-R^b, -R^a-CO-OR^b, -R^aO-CO-R^b, -R^a-CO-N(R^b)₂, -R^a-NR^b-CO-R^b, -R^aO-CO-OR^b, -RO-CO-N(R^b)₂, -R^a-NR^b-CO-OR^b, -R^a-NR^b-CO-N(R^b)₂, -R^a-CS-R^b, -R^a-CS-OR^b, -RO-CS-R^b, -R^a-CS-N(R^b)₂, -R^a-NR^b-CS-R^b, -R^aO-CS-OR^b, -R^aO-CS-N(R^b)₂, -R^a-NR^b-CS-OR^b, -R^a-NR^b-CS-N(R^b)₂, or -R^b;

preferably independently one or more of the hydroxyl groups of the monosaccharide subunit is replaced with -H, -F, -CI, -Br, -I, -CF₃, -CCL, -CBr₃, -CI₃, -SH, -NH₂, -N₃, -NH=NH₂, -CN, -N0₂, -COOH, -R^a-0-R^b, -R^a-S-R^b, -SO-R^b, -S0₂-R^b, -S0₂-OR^b, -0-S0₂-R^b, -0-S0₂-OR^b, -R^a-N(R^b)₂, -R^a-N(R^b)₃ ⁺, -R^a-Si(R^b)₃, -R^a-CO-R^b, -R^a-CO-OR^b, -RO-CO-R^b, -R^a-CO-N(R^b)₂, -R^a-NR^b-CO-R^b,

-R^aO-CO-OR^b, -R^a-CS-R^b, or -R^b; and/or

(b) independently one, two or three of the hydrogens of the monosaccharide subunit is replaced with -F, -CI, -Br, -I, -CF₃, -CC1₃, -CBr₃, -CI₃, -OH, -SH, -NH₂, -N₃, -NH=NH₂, -CN, -N0₂, -COOH, -R^a-0-R^b, -R^a-S-R^b,

-R^a-SO-R^b, -R^a-S0₂-R^b, -R^a-S0₂-OR^b, -R^aO-S0₂-R^b, -R^a-S0₂-N(R^b)₂, -R^a-NR^b-S0₂-R^b,

-R^aO-S0₂-OR^b, -R^aO-S0₂-N(R^b)₂, -R^a-NR^b-SO_z-OR^b, -R^a-NR^b-S0₂-N(R^b)₂,

-R^a-N(R^b)₂, -R^a-N(R^b)₃ ⁺, -R^a-B(R^b)₂, -R^a-P(R^b)₂, -R^a-PO(R^b)₂, -R^a-Si(R^b)₃, -R^a-CO-R^b,

-R^a-CO-OR^b, -R^aO-CO-R^b, -R^a-CO-N(R^b)₂, -R^a-NR^b-CO-R^b, -R^aO-CO-OR^b, -RO-CO-N(R^b)₂, -R -NR^b-CO-OR , -R^a-NR^b-CO-N(R^b)₂, -R^a-CS-R^b, -R^a-CS-OR^b,

-R^aO-CS-R^b, -R^a-CS-N(R^b)₂, -R^a-NR^b-CS-R^b, -R^aO-CS-OR^b, -R^aO-CS-N(R^b)₂,

-R^a-NR^b-CS-OR^b, -R^a-NR^b-CS-N(R^b)₂, or -R^b;

preferably independently one, two or three of the hydrogens of the monosaccharide subunit is replaced with -F, -CI, -Br, -I, -CF₃, -CC1₃, -CBr₃, -CI₃, -OH, -SH, -NH₂, -N₃, -NH=NH₂, -CN, -N0₂, -COOH, -R^a-0-R^b, -R^a-S-R^b, -SO-R^b,

-S0₂-R^b, -S0₂-OR^b, -0-S0₂-R^b, -R^aO-S0₂-OR^b, -R -N(R^b)₂, -R^a-N(R^b)₃ ⁺, -R^a-Si(R^b)₃,

-R^a-CO-R^b, -R^a-CO-OR^b, -RO-CO-R^b, -R^a-CO-N(R^b)₂, -R^a-NR^b-CO-R^b,

-R^aO-CO-OR^b, -R^a-CS-R^b, or -R^b; and/or

(c) independently one or more of the hydroxyl groups of the monosaccharide subunit, together with the hydrogen attached to the same carbon atom as the hydroxyl group, is replaced with =0, =S, =NR^b, or =N(R^b)₂ ⁺; and/or

(d) independently two hydroxyl groups of the monosaccharide subunit are together replaced with -0-R^c-, -S-R^c-, -SO-R^c-, -S0₂-R^c-, or -NR^b-R^c-;

wherein:

-R^a- is independently a chemical bond, or a substituted or unsubstituted alkylene, alkenylene or alkynylene group which optionally includes one or more heteroatoms in its carbon skeleton and preferably comprises 1 -10 carbon atoms;

-R^b is independently hydrogen, an optionally substituted monosaccharide subunit, or a substituted or unsubstituted, straight-chain, branched or cyclic alkyl, alkenyl, alkynyl, acyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, alkylaryl, alkenylaryl or alkynylaryl group which optionally includes one or more heteroatoms in its carbon skeleton and preferably comprises 1-15 carbon atoms; -R^c- is independently a chemical bond, or a substituted or unsubstituted alkylene, alkenylene or alkynylene group which optionally includes one or more heteroatoms in its carbon skeleton and preferably comprises 1-10 carbon atoms; and

M is a metal;

provided that the monosaccharide subunit comprises at least one -OR^b,

-OSOR^b,

-OS0₃R^b, -OSi(R^b)₃, -OCOR^b, -OCO_zR^b, or -OM.

Preferably any substituted monosaccharide subunit comprises at least one, at least two, at least three or at least four -OR^b, -OSOR , -OS0₂R^b, -OS0₃R^b, -OSi(R^b)₃, -OCOR^b, -OC0₂R^b, or -OM. More preferably any substituted monosaccharide subunit comprises at least one, at least two, at least three or at least four -OR^b or -OM.

In a modified monosaccharide subunit:

(a) the ring of the modified monosaccharide subunit, or what would be the ring in the ring-closed form of the modified monosaccharide subunit, is partially unsaturated; and/ or

(b) the ring oxygen of the modified monosaccharide subunit, or what would be the ring oxygen in the ring-closed form of the modified monosaccharide subunit, is replaced with -S- or -NR^b-, wherein -R is independently hydrogen, an optionally substituted monosaccharide subunit, or a substituted or unsubstituted, straight-chain, branched or cyclic alkyl, alkenyl, alkynyl, acyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, alkylaryl, alkenylaryl or alkynylaryl group which optionally includes one or more heteroatoms in its carbon skeleton and preferably comprises 1-15 carbon atoms.

Each hydrocarbyl group independently may be a substituted or unsubstituted, straight-chain, branched or cyclic alkyl, alkenyl, alkynyl, acyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, alkylaryl, alkenylaryl or alkynylaryl group which optionally comprises 1-15 carbon atoms and optionally includes one or more heteroatoms in its carbon skeleton. Preferably a hydrocarbyl group comprises 1-12, 1-6 or 1-4 carbon atoms. A substituted hydrocarbyl group may be substituted with one or more of -F, -CI, -Br, -I, -CF₃, -CCI₃, -CBr₃, -CI₃, -OH, -SH, -NH₂, -N₃, -NH=NH₂, -CN, -N0₂, -COOH, -R^a-0-R^b, -R^a-S-R^b, -R^a-SO-R^b, -R^a-S0₂-R^b, -R^a-S0₂-OR^b, -R^aO-S0₂-R^b, -R^a-S0₂-N(R^b)₂, -R^a-NR^b-S0₂-R , -RO-S0₂-OR^b, -R^aO-S0₂-N(R^b)₂, -R^a-NR^b-S0₂-OR^b, -R^a-NR^b-S0₂-N(R^b)₂, -R^a-N(R^b)₂, -R^a-N(R^b)₃ ⁺, -R^a-B(R^b)₂, -R^a-P(R^b)₂, -R^a-PO(R^b)₂, -R^a-Si(R^b)₃, -R^a-CO-R^b, -R^a-CO-OR^b, -R^aO-CO-R^b, -R^a-CO-N(R^b)₂,

-R^aO-CO-OR^b, -R^aO-CO-N(R^b)₂,

-R^a-NR^b-CO-OR^b, -R^a-NR^b-CO-N(R^b)₂, -R^a-CS-R^b, -R^a-CS-OR^b, -R^aO-CS-R^b, -R^a-CS-N(R^b)₂, -R^a-NR^b-CS-R , -RO-CS-OR^b, -R^aO-CS-N(R^b)₂, -R^a-NR^b-CS-OR^b, -R^a-NR^b-CS-N(R^b)₂, -R^b, or a monosaccharide subunit;

preferably a substituted hydrocarbyl group may be substituted with one or more of -F, -CI, -Br, -I, -CF₃, -CC1₃, -CBr₃, -CI₃, -OH, -SH, -NH₂, -N₃, -NH=NH₂, -CN, -N0₂, -COOH, -R^a-0-R^b, -R^a-S-R^b, -SO-R^b, -S0₂-R^b, -S0₂-OR^b, -0-S0₂-R^b, -0-S0₂-OR^b, -R^a-N(R^b)₂, -R^a-N(R^b)₃ ⁺, -R^a-Si(R^b)₃, -R^a-CO-R^b, -R^a-CO-OR^b, -R^aO-CO-R^b, -R^a-CO-N(R^b)₂, -R^a-NR^b-CO-R^b, -R^aO-CO-OR^b, -R^a-CS-R^b, -R^b, or a monosaccharide subunit;

wherein:

-R - is independently a chemical bond, or a substituted or unsubstituted alkylene, alkenylene or alkynylene group which optionally includes one or more heteroatoms in its carbon skeleton and preferably comprises 1-10 carbon atoms; and -R^b is independently hydrogen, an optionally substituted monosaccharide subunit, or a substituted or unsubstituted, straight-chain, branched or cyclic alkyl, alkenyl, alkynyl, acyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, alkylaryl, alkenylaryl or alkynylaryl group which optionally includes one or more heteroatoms in its carbon skeleton and preferably comprises 1-15 carbon atoms.

In one embodiment of the present invention, each R group that is not hydrogen contains 1-25 or 1-20 carbon atoms. In another embodiment, each R group that is not hydrogen contains 1-12 carbon atoms. For instance, each R group that is not hydrogen may contain 1-7, 1-6, 1-5 or 1-4 carbon atoms.

In one embodiment of the present invention, one R group that is not hydrogen contains 1-25 or 1-20 carbon atoms. In another embodiment of the present invention, one R group that is not hydrogen contains 1-12 carbon atoms. For instance, one R group that is not hydrogen may contain 1-7, 1-6, 1-5 or 1-4 carbon atoms. Preferably said R group is a hydrocarbyl group. All monosaccharide subunits are independently in the D- or L-configuration.

The stereochemistry of each glycosidic bond is independently a or β.

In one embodiment of the present invention, two R groups and the nitrogen atom to which they are attached, together do not form a heterocyclic aromatic group. In another embodiment, the glycosylamine is not a nucleoside and/ or not a nucleotide. In yet another embodiment, the glycosylamine does not comprise a ribose subunit comprising a glycosidic tertiary amine. In one embodiment of the present invention, none of the monosaccharide subunits is pyranosyl with N-substitution at the 2-position relative to the anomeric carbon of the pyranosyl subunit. Preferably none of the monosaccharide subunits is -NH-hydrocarbyl substituted a to the anomeric carbon. Preferably none of the monosaccharide subunits is iV-substituted a to the anomeric carbon.

In one embodiment of the present invention, none of the monosaccharide subunits is pyranosyl with a -C0₂Q group attached to the 5-position relative to the anomeric carbon of the pyranosyl subunit, wherein Q is hydrogen or a hydrocarbyl group. Preferably, none of the monosaccharide subunits has a -C0₂Q group attached to the 5-position and/ or the ω-position relative to the anomeric carbon of the monosaccharide subunit. Preferably, none of the monosaccharide subunits is substituted with a -C0₂Q group.

In one embodiment of the present invention, the glycosylamine contains no sulphate groups.

Preferred glycosylamines for use in the invention include:

(a) glucosylamines; (b) 1-benzamido-l-deoxy-glucose;

(c) 1 -JV-octyl- 1 -iV-decanoyl-1 -amino- 1 -deoxy-muramyl-D-isoglutamyl- alanine;

(d) β,β-di-glucosylamine;

(e) JV-acetyl-P, -di-glucosylamine

(f) N-ethyl-P, -di-glucosylamine; and

(g) di- (4,4' -gluco sylgluco syl) amine .

In one embodiment of the present invention, the glycosylamine further comprises at least one sulphate group, wherein a sulphate group is a -0-S0₂-OR , -NR -S0₂-OR , -0-S0₂-N(R)₂ or -NR -S0₂-N(R)₂ group, wherein each R is independently hydrogen, a metal, a further monosaccharide subunit, or a hydrocarbyl group. Preferably the glycosylamine comprises at least two or at least three sulphate groups.

Thus, the glycosylamine comprising at least one sulphate group may be any as described in WO 2008/059003, which is hereby incorporated herein by reference in its entirety. Preferably the sulphate groups are selected from -0-S0₂-OR , -NR -S0₂-OR or -0-S0₂-N(R)₂ groups. More preferably the sulphate groups are -OS0₃R groups.

In another embodiment the glycosylamine comprises at least two monosaccharide subunits, each of which is substituted with at least one sulphate group.

In yet another embodiment, 1-50, or 2-30, or 3-15, or 6-12, or all the hydroxyl groups on the monosaccharide subunits independently have been replaced with a sulphate group. The specified range relates to the total number of hydroxyl groups that have been replaced with a sulphate group across all the monosaccharide subunits within the compound.

In still another embodiment, 1-9, or 2-8, or 3-4 hydroxyl groups on each of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12 or all monosaccharide subunits independently have been replaced with a sulphate group. Here, the specified range relates to the number of hydroxyl groups that have been replaced with a sulphate group per individual monosaccharide subunit within the compound, and the specified number relates to the number of monosaccharide subunits on which the specified replacement has occurred.

Optionally in any of the above embodiments, each R is independently hydrogen, a metal, or a substituted or unsubstituted, straight-chain, branched or cyclic alkyl, alkenyl, alkynyl, acyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, alkylaryl, alkenylaryl or alkynylaryl group which optionally includes one or more heteroatoms in its carbon skeleton. Preferably each R is independently hydrogen, an alkali metal, an alkali earth metal, copper, silver, zinc, or a C C₆ alkyl group.

When R^' is a metal, then typically -OS0₃R^' is -OS0₃ ^" Li⁺, -OS0₃ ^" Na⁺, -OS0₃ ^" K⁺, -OS0₃ ^" Cu⁺, -OS0₃ ^~ Ag⁺, -OS0₃ ^~ (Al₂(OH)₅)⁺, or two -OS0₃R^' together are (-OS0₃ ^~)₂ Mg²⁺, (-OS0₃ ^~)₂ Ca²⁺, (-OS0₃ ^")₂ Cu²⁺, or (-OS0₃ ^~)₂ Zn²⁺, or three -OS0₃R together are (-OS0₃ ^~)₃ Al³⁺; typical -NR -S0₂-OR groups comprise the same metal cations. Examples of preferred sulphated glycosylamines for use in the present invention include:

(a) a sulphated glucosylamine;

(b) l-benzamido-l-deoxy-2,3,4,6-tetra potassium sulphonatoglucose;

(c) 1-iV-octyl-l -JV-decanoyl-1 -amino-l-deoxy-6-potassium sulphonate- muramyl-D-isoglutamyl-alanine;

(d) a mono-, di-, tri-, tetra-, penta-, hexa-, hepta- or octasulphated β,β-di- glucosylamine, or a mixture thereof;

(e) a mono-, di-, tri-, tetra-, penta-, hexa-, hepta- or octasulphated N-acetyl-P,P-di-glucosylamine, or a mixture thereof;

(f) a mono-, di-, tri-, tetra-, penta-, hexa-, hepta- or octasulphated

AT-ethyl-P,P-di-glucosylamine, or a mixture thereof; and

(g) a sulphated di-(4,4'-glucosylglucosyl)amine. In a preferred embodiment of the present invention, the glycosylamine has formula (I):

wherein:

R is H, Ac, Me, Et, COCF₃, or COPh;

each R is S0₃R or H; and

each R^' is H, Li, Na or K;

or a stereoisomer thereof. Preferably in such an embodiment:

(a) R is Ac and all R are H; or

(b) R is H and all R^" are H.

In another preferred embodiment of the present invention, the glycosylamine the formula (II):

R is H, Ac, Me, Et, COCF₃, or COPh;

each R is S0₃R or H; and

each R^' is H, Li, Na or K;

stereoisomer thereof.

In another preferred embodiment of the present invention, the glycosylamine has the formula (III):

wherein:

R is H, CHO or COMe;

R is S0₃R or H; and

R^' is H, Li, Na or K;

or a stereoisomer thereof.

In another preferred embodiment of the present invention, the glycosylamine the formula (IV):

(IV)

wherein:

R is H, Ac, Me, Et, COCF₃, or COPh;

each R is S0₃R or H; and

each R is H, Li, Na or K;

or a stereoisomer thereof. Preferably in such an embodiment R is H or Ac and all R are H.

In one embodiment of the first or second aspects of the present invention, the pharmaceutical composition or kit comprises a glycosyl-precursor and/ or an amine- precursor of a glycosylamine according to any of the preceding embodiments of the present invention. Optionally such a pharmaceutical composition or kit further comprises a glycosylamine according to any of the preceding embodiments of the present invention.

Preferably, the glycosyl-precursor comprises:

(a) a glycosidic -OH group in place of a glycosidic -NR₂ group or a glycosidic -NR₃ ⁺ group of the glycosylamine; or

(b) a directly bonded =0 group in place of a directly bonded =NR group or a directly bonded =NR₂ ⁺ group of the glycosylamine. The glycosyl-precursor may for instance be a monosaccharide, such as glucose and in particular D-glucose, or a poly- or oligosaccharide, such as starch, maltose, glycogen and lactose.

The amine-precursor may be for instance NH₃, NH₂R, NHR₂ or NR₃, wherein R is as defined above, with the proviso that R is not hydrogen. In one embodiment an acid addition salt of the amine-precursor is used. The amine-precursor may for instance be an ammonium salt, such as ammonium carbonate, ammonium bicarbonate, ammonium sulphate and ammonium magnesium sulphate. The glycosyl-precursor and the amine-precursor together can generate a glycosylamine according to the present invention. The glycosyl-precursor when used without an amine-precursor can generate a glycosylamine according to the present invention together with a nitrogen source already present in the patient to be treated. The amine-precursor when used without a glycosyl-precursor can generate a glycosylamine according to the present invention together with a saccharide source already present in the patient to be treated.

Where a pharmaceutical composition or kit of the present invention comprises both a glycosyl-precursor and an amine-precursor, said precursors may form part of the same or separate pharmaceutical compositions. Preferably said precursors form part of the same pharmaceutical composition. A third aspect of the present invention relates to a pharmaceutical composition of the first or second aspects of the present invention, further comprising a third active pharmaceutical ingredient, or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof.

A fourth aspect of the present invention relates to a pharmaceutical kit comprising a pharmaceutical composition of the first or second aspects of the present invention, and a third active pharmaceutical ingredient, or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof.

In one embodiment of the fourth aspect of the present invention, said third active pharmaceutical ingredient or pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof forms part of a second pharmaceutical composition. A fifth aspect of the present invention relates to a pharmaceutical kit of the first or second aspects of the present invention, further comprising a third active pharmaceutical ingredient, or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof. In the pharmaceutical kit of the first, second, fourth or fifth aspects of the present invention:

(a) the anti-inflammatory or antibacterial agent or pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof may form part of a first pharmaceutical composition; and/or

(b) the glycosylamine or precursor(s) thereof, or pharmaceutically acceptable tautomer, salt, prodrug or hydrate of said glycosylamine or precurso (s), may form part of a second pharmaceutical composition; and/or

(c) if present, the third active pharmaceutical ingredient or pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof may form part of a third pharmaceutical composition.

In one embodiment of the fourth or fifth aspects of the present invention: (a) the anti-inflammatory or antibacterial agent or pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof, and

(c) the third active pharmaceutical ingredient or pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof,

form part of the same pharmaceutical composition.

In another embodiment of the fourth or fifth aspects of the present invention:

(b) the glycosylamine or precursor(s) thereof, or pharmaceutically acceptable tautomer, salt, prodrug or hydrate of said glycosylamine or precursor(s), and

form part of the same pharmaceutical composition. In one embodiment of any of the third, fourth or fifth aspects of the present invention, the third active pharmaceutical ingredient may be any other antiinflammatory or antibacterial agent, such as those listed in relation to the first and second aspects of the present invention. Thus where the pharmaceutical composition or kit comprises an anti-inflammatory or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof, the third active pharmaceutical ingredient may be selected from antibacterial agents or pharmaceutically acceptable tautomers, salts, prodrugs and hydrates thereof. Preferably the third active pharmaceutical ingredient is selected from antibiotics, synthetic antibacterial agents, or pharmaceutically acceptable tautomers, salts, prodrugs and hydrates thereof. Most preferably the third active pharmaceutical ingredient is an antibiotic or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof. Similarly, where the pharmaceutical composition or kit comprises an antibacterial agent or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof, the third active pharmaceutical ingredient may be selected from anti-inflammatories or pharmaceutically acceptable tautomers, salts, prodrugs and hydrates thereof. Preferably the third active pharmaceutical ingredient is selected from COX- inhibitors, steroids, anti-interleukin-6 agents, sulphated saccharides or pharmaceutically acceptable tautomers, salts, prodrugs and hydrates thereof. Most preferably the third active pharmaceutical ingredient is a COX-inhibitor such as aspirin, or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof.

Alternatively where the pharmaceutical composition or kit comprises an antiinflammatory or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof, the third active pharmaceutical ingredient may be a second anti- inflammatory or pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof. Preferably, where the first anti-inflammatory is a COX-inhibitor such as aspirin, or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof, said second anti-inflammatory is selected from steroids, anti-interleukin-6 agents, sulphated saccharides or pharmaceutically acceptable tautomers, salts, prodrugs and hydrates thereof.

Alternatively still where the pharmaceutical composition or kit comprises an antibacterial agent or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof, the third active pharmaceutical ingredient may be a second antibacterial agent or pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof. For instance, where the first antibacterial agent is an antibiotic or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof, said second antibacterial agent may be selected from synthetic antibacterial agents or pharmaceutically acceptable tautomers, salts, prodrugs and hydrates thereof. Alternatively, where the first antibacterial agent is an antibiotic, a synthetic antibacterial agent, a leprostatic agent, an anti-rickettsial agent or a tuberculostatic agent, or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof, said second antibacterial agent may selected from antibacterial adjuncts or pharmaceutically acceptable tautomers, salts, prodrugs and hydrates thereof.

The following paragraphs apply equally to all aspects of the present invention. In one embodiment, any compound such as the glycosylamine, precursor, antiinflammatory, antibacterial agent and/ or third active pharmaceutical ingredient used in the present invention may be a pharmaceutically acceptable salt. The compounds can be used both, in their free base form and their acid addition salt form. For the purposes of this invention, a 'salt' of a compound of the present invention can be an acid addition salt. Acid addition salts are preferably pharmaceutically acceptable, non-toxic addition salts with suitable acids, including but not limited to inorganic acids such as hydrohalogenic acids (for example, hydrofluoric, hydrochloric, hydrobromic or hydroiodic acid) or other inorganic acids (for example, nitric, perchloric, sulphuric or phosphoric acid); or organic acids such as organic carboxylic acids (for example, propionic, butyric, glycolic, lactic, mandelic, citric, acetic, benzoic, salicylic, succinic, malic or hydroxysuccinic, tartaric, fumaric, maleic, hydroxymaleic, mucic or galactaric, gluconic, pantothenic or pamoic acid), organic sulphonic acids (for example, methanesulphonic, trifluoromethanesulphonic, ethanesulphonic, 2-hydroxyethanesulphonic, benzenesulphonic, toluene-p-sulphonic, naphthalene-2-sulphonic or camphorsulphonic acid) or amino acids (for example, ornithinic, glutamic or aspartic acid). A preferred salt is a hydrohalogenic, sulphuric, phosphoric or organic acid addition salt. The acid addition salt may be a mono-, di-, tri-, tetra- or multi- acid addition salt, or a mixture thereof.

The compounds can also be used both, in their free acid form and their salt form. For the purposes of this invention, a 'salt' of a compound of the present invention can also be formed between a carboxylic acid, sulphate, or other suitable functionality of a compound of the present invention and a suitable cation. Suitable cations include, but are not limited to, alkali metal cations such as lithium, sodium and potassium cations, alkali earth metal cations such as magnesium and calcium cations, transition metal cations such as zinc, copper, zirconium, titanium, manganese, osmium and iron cations, aluminium cations such as [Al₂(OH)₅]⁺, carbocations, and ammonium cations such as ammonium, HOCH₂CH₂NH₃ ⁺, (HOCH₂CH₂)₂NH₂ ⁺, (HOCH₂CH₂)₃NH⁺, ^NI¾ , H⁺ _ NH_{2 AND QUATEMARY} ammonium cations such as choline cation. Preferred cations include sodium, potassium, magnesium, calcium, ammonium and choline cations. The salt may be a mono-, di-, tri-, tetra- or multi-salt, or a mixture thereof.

Preferably the salt of a sulphated glycosylamine is a multi-sodium, potassium, magnesium, calcium, aluminium, ammonium or choline salt. More preferably the salt is a multi-potassium salt. In one embodiment of the present invention, each sulphate group of a compound of the present invention exists in its salt form.

The present invention encompasses the use of pharmaceutically acceptable salts, derivatives, solvates, clathrates and/or hydrates (including anhydrous forms) of the compounds used in the present invention.

The present invention also encompasses the use of quaternary ammonium salts of the glycosylamines used in the present invention, wherein the nitrogen of the glycosidic amine group is further substituted by a substituent other than hydrogen, resulting in a positive charge on the nitrogen, balanced by a suitable counter-anion. Preferably the substituent is alkyl, preferably methyl or ethyl. Suitable counter- anions include any of those formed in the process of generating acid addition salts as discussed above. Preferably the present invention does not use quaternary ammonium salts of glycosylamines.

It is preferred that any compound or pharmaceutically acceptable salt form of any compound used in any aspect of the present invention is water soluble. As used herein, the term 'water soluble' refers to a form wherein at least 1 g of said compound or pharmaceutically acceptable salt will dissolve in 10 hires of water, preferably at a pH of 10 or less. Preferably, at least 1 g of said compound or pharmaceutically acceptable salt will dissolve in 1 litre, 100 ml, 30 ml, 10 ml or more preferably 1 ml of water. The compounds used in the present invention may contain one or more chiral centres. The compounds may therefore exist in two or more stereoisomeric forms. The present invention independently encompasses the use of racemic mixtures of each of the compounds as well as enantiomerically enriched and substantially enantiomerically pure isomers of each of the compounds. For the purposes of this invention, a 'substantially enantiomerically pure' isomer of a compound comprises less than 5% of other isomers of the same compound, preferably less then 3%, preferably less than 2%, preferably less than 1%, preferably less than 0.5%. For the purposes of all aspects of the present invention, an 'alkyP group is defined as a monovalent saturated hydrocarbon, which may be straight-chained or branched, or be or include cyclic groups. Examples of alkyl groups are methyl, ethyl, //-propyl, /-propyl, //-butyl, /-butyl, /'-butyl and //-pentyl groups. Preferably an alkyl group is straight-chained or branched and does not include any heteroatoms in its carbon skeleton. Preferably an alkyl group is a C_rC₁₂ alkyl group, which is defined as an alkyl group containing from 1 to 12 carbon atoms. More preferably an alkyl group is a Cj-C₆ alkyl group, which is defined as an alkyl group containing from 1 to 6 carbon atoms. An alkyl group may also be a C C₄ alkyl group, which is defined as an alkyl group containing from 1 to 4 carbon atoms. An 'alkylene' group is similarly defined as a divalent alkyl group.

An 'alkenyl' group is defined as a monovalent hydrocarbon, which comprises at least one carbon-carbon double bond, which may be straight-chained or branched, or be or include cyclic groups. Examples of alkenyl groups are vinyl, allyl, but-l-enyl and but-2-enyl groups. Preferably an alkenyl group is straight-chained or branched and does not include any heteroatoms in its carbon skeleton. Preferably an alkenyl group is a C₂-C₁₂ alkenyl group, which is defined as an alkenyl group containing from 2 to 12 carbon atoms. More preferably an alkenyl group is a C₂-C₆ alkenyl group, which is defined as an alkenyl group containing from 2 to 6 carbon atoms. An alkenyl group may also be a C₂-C₄ alkenyl group, which is defined as an alkenyl group containing from 2 to 4 carbon atoms. An 'alkenylene' group is similarly defined as a divalent alkenyl group. An 'alkynyl' group is defined as a monovalent hydrocarbon, which comprises at least one carbon-carbon triple bond, which may be straight-chained or branched, or be or include cyclic groups. Examples of alkynyl groups are ethynyl, propargyl, but- 1-ynyl and but-2-ynyl groups. Preferably an alkynyl group is straight- chained or branched and does not include any heteroatoms in its carbon skeleton. Preferably an alkynyl group is a C₂-C₁₂ alkynyl group, which is defined as an alkynyl group containing from 2 to 12 carbon atoms. More preferably an alkynyl group is a C₂-C₆ alkynyl group, which is defined as an alkynyl group containing from 2 to 6 carbon atoms. An alkynyl group may also be a C₂-C₄ alkynyl group, which is defined as an alkynyl group containing from 2 to 4 carbon atoms. An 'alkynylene' group is similarly defined as a divalent alkynyl group.

An 'acyP group is defined as a -COR^x group, wherein R^x is hydrogen, or an optionally substituted alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, alkylaryl, alkenylaryl or alkynylaryl group. Examples of acyl groups are formyl, acetyl, trifluoroacetyl, propanoyl and benzoyl groups. Preferably an acyl group is straight-chained or branched and does not include any heteroatoms in its carbon skeleton. Preferably an acyl group is a Q-C^ acyl group, which is defined as an acyl group containing from 1 to 15 carbon atoms. More preferably an acyl group is a C₁-C_n acyl group, which is defined as an acyl group containing from 1 to 12 carbon atoms. More preferably an acyl group is a Q-Q acyl group, which is defined as an acyl group containing from 1 to 6 carbon atoms. An acyl group may also be a Q-C₄ acyl group, which is defined as an acyl group containing from 1 to 4 carbon atoms. An acyl group may also contain 1 , 2, 3, 4, 5 or 6 carbon atoms.

An 'aryl' group is defined as a monovalent aromatic hydrocarbon. Examples of aryl groups are phenyl, naphthyl, anthracenyl and phenanthrenyl groups. Preferably an aryl group does not include any heteroatoms in its carbon skeleton. Preferably an aryl group is a C₄-C₁₄ aryl group, which is defined as an aryl group containing from 4 to 14 carbon atoms. More preferably an aryl group is a C₆-C₁₀ aryl group, which is defined as an aryl group containing from 6 to 10 carbon atoms. An 'arylene' group is similarly defined as a divalent aryl group. For the purposes of the present invention, where a combination of groups is referred to as one moiety, for example, arylalkyl, arylalkenyl, arylalkynyl, alkylaryl, alkenylaryl or alkynylaryl, the last mentioned group contains the atom by which the moiety is attached to the rest of the molecule. A typical example of an arylalkyl group is benzyl.

For the purposes of this invention, a substituted group may be substituted monovalently with one or more of -F, -CI, -Br, -I, -CF₃, -CC1₃, -CBr₃, -CI₃, -OH, -SH, -NH₂, -N₃, -NH=NH₂, -CN, -N0₂, -COOH, -R^p-0-R^Y, -R^P-S-R^Y, -R^p-SO-R^Y, -R^p-S0₂-R^Y, -R^p-S0₂-OR^Y, -R^pO-SO_z-R^Y, -R^p-S0₂-N(R^Y)₂, -R^p-NR^Y-S0₂-R^Y, -R^pO-S0₂-OR^Y, -R^pO-S0₂-N(R^Y)₂, -R^p-NR^Y-S0₂-OR^Y, -R^p-NR^Y-S0₂-N(R^Y)₂, -R^P-N(R^Y)₂, -R^P-N(R^Y)₃ ⁺, -R^P-B(R^Y)₂, -R^P-P(R^Y)₂, -R^p-PO(R^Y)₂, -R^p-Si(R^Y)₃, -R^p-CO-R^Y, -R^p-CO-OR^Y, -R^pO-CO-R^Y, -R^p-CO-N(R^Y)₂, -R^p-NR^Y-CO-R^Y, -R^pO-CO-OR^Y, -R^pO-CO-N(R^Y)₂, -R^p-NR^Y-CO-OR^Y, -R^p-NR^Y-CO-N(R^Y)₂, -R^P-CS-R^Y, -R^p-CS-OR^Y, -R^pO-CS-R^Y, -R^P-CS-N(R^Y)₂, -R^P-NR^Y-CS-R^Y, -R^pO-CS-OR^Y, -R^pO-CS-N(R^Y)₂, -R^p-NR^Y-CS-OR^Y, -R^P-NR^Y-CS-N(R^Y)₂, or -R^Y; preferably monovalently with one or more of -F, -CI, -Br, -I, -CF₃, -CC1₃, -CBr₃, -CI₃, -OH, -SH, -NH₂, -N₃, -NH=NH₂, -CN, -N0₂, -COOH, -R^p-0-R^Y, -R^P-S-R^Y, -SO-R^Y, -S0₂-R^Y, -S0₂-OR^Y, -0-S0₂-R^Y, -0-S0₂-OR^Y, -R^P-N(R^Y)₂, -R^P-N(R^Y)₃ ⁺, -R^p-Si(R^Y)₃, -R^p-CO-R^Y, -R^p-CO-OR^Y, -R^pO-CO-R^Y, -R^p-CO-N(R^Y)₂, -R^p-NR^Y-CO-R^Y, -R^pO-CO-OR^Y, -R^P-CS-R^Y, or -R^Y; or divalently with one or more of -R^p-,— O, =S, or =NR^Y; or trivalently with one or more of =N-R^P-. In this context, -R^p- is independently a chemical bond, or a substituted or unsubstituted alkylene, alkenylene or alkynylene group, optionally including one or more heteroatoms in its carbon skeleton. -R^Y is independently hydrogen, or a substituted or unsubstituted alkyl or aryl group, optionally including one or more heteroatoms in its carbon skeleton. Optional substituent(s) are not taken into account when calculating the total number of carbon atoms in the parent group substituted with the optional substituent(s). Preferably the total number of carbon atoms in any given -R^Y or -R^p- group, including any further substitution on that group, is 1-50, preferably 1-20, preferably 1-10, preferably 1-6. Preferably a substituted group comprises 1, 2 or 3 substituents, preferably 1 or 2 substituents, preferably 1 substituent. Any optional substituent, for example on a monosaccharide subunit or on a hydrocarbyl group, may be protected. Suitable protecting groups for protecting optional substituents are known in the art, for example from 'Protective Groups in Organic Synthesis' by Theodora W. Greene and Peter G. M. Wuts (Wiley- Interscience, 4th edition, 2006).

For the purposes of this invention, a heteroatom is preferably a B, Si, N, P, O or S atom; more preferably a heteroatom is a N, O or S atom. Any pharmaceutical composition or kit in any of the above aspects of the present invention may independently optionally comprise one or more pharmaceutically acceptable excipients.

Similarly, any pharmaceutical composition or kit in any of the above aspects of the present invention may independently be for oral, parenteral (including intravenous, subcutaneous, intramuscular, intradermal, intratracheal, intraperitoneal, intraarticular, intracranial and epidural), transdermal, airway (aerosol), rectal, vaginal or topical (including buccal, mucosal and sublingual) administration. In one embodiment of the present invention, at least one pharmaceutical composition is for topical or transdermal administration. Every pharmaceutical composition may be for topical or transdermal administration. Preferably each pharmaceutical composition for topical or transdermal administration is independently in the form of an ointment, cataplasm (poultice), paste, powder, dressing, cream, plaster or patch.

Where a pharmaceutical composition is for topical or transdermal administration, said composition may comprise an antibacterial agent such as an antibiotic, or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof. Alternately said composition may comprise an anti-inflammatory such as a COX inhibitor or a steroid, or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof. Preferably said composition comprises both an antibacterial agent and an anti- inflammatory, or pharmaceutically acceptable tautomers, salts, prodrugs or hydrates thereof.

In another embodiment of the present invention, at least one pharmaceutical composition is for oral administration. Every pharmaceutical composition may be for oral administration. Preferably each pharmaceutical composition for oral administration is independently a tablet, capsule, caplet, troche, lozenge, or is in the form of a powder, granules, an aqueous solution, suspension or dispersion. Most preferably each pharmaceutical composition for oral administration is a tablet.

Tablets for oral use may include the active pharmaceutical ingredient(s) mixed with pharmaceutically acceptable excipients such as inert diluents, disintegrating agents, binding agents, lubricating agents, sweetening agents, flavouring agents, colouring agents and preservatives. Suitable inert diluents include sodium and calcium carbonate, sodium and calcium phosphate, and lactose. Com starch and alginic acid are suitable disintegrating agents. Binding agents may include starch and gelatine. The lubricating agent, if present, may be magnesium stearate, stearic acid or talc. If desired, the tablets may be coated with a material, such as glyceryl monostearate or glyceryl distearate, to delay absorption in the gastrointestinal tract.

Capsules for oral use include hard gelatine capsules in which the active ingredient is mixed with a solid diluent, and soft gelatine capsules wherein the active ingredient is mixed with water or an oil such as peanut oil, liquid paraffin or olive oil. Optionally, a pharmaceutical composition for oral administration may comprise an enteric coating. In one embodiment, any pharmaceutical composition comprising the anti-inflammatory and/ or antibacterial agent, or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof, comprises an enteric coating. Preferably 50%, 75%, 90%, 95%, 99% or all of the anti-inflammatory and/or antibacterial agent, or pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof, present within a pharmaceutical composition is encompassed by an enteric coating. In another embodiment, any pharmaceutical composition comprising the glycosylamine or one or more precursors thereof, or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate of said glycosylamine or precursor(s), comprises an enteric coating. Preferably 50%, 75%, 90%, 95%, 99% or all of the glycosylamine or one or more precursors thereof, or pharmaceutically acceptable tautomer, salt, prodrug or hydrate of said glycosylamine or precursor(s), present within a pharmaceutical composition is encompassed by an enteric coating.

Where a pharmaceutical composition comprises a glycosyl-precursor of a glycosylamine, or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate of said precursor, it is preferred that said pharmaceutical composition also comprises an enteric coating. More preferably, 50%, 75%, 90%, 95%, 99% or all of said glycosyl-precursor, or pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof, is encompassed by the enteric coating.

Where a pharmaceutical composition comprises an amine-precursor of a glycosylamine, or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate of said precursor, it is preferred that said pharmaceutical composition also comprises an enteric coating. More preferably, 50%, 75%, 90%, 95%, 99% or all of said amine-precursor, or pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof, is encompassed by the enteric coating.

In one embodiment, any pharmaceutical composition comprising any active pharmaceutical ingredient comprises an enteric coating. Preferably 90%, 95%, 99% or all of the active pharmaceutical ingredients present within a pharmaceutical composition are encompassed by an enteric coating.

Each enteric coating may be selected from acrylic copolymers such as methacrylic acid-methacrylic acid ester and methacrylic acid-acrylic acid ester copolymers; polyvinyl acetate phthalate; hydroxypropyl methylcellulose phthalate; cellulose acetate phthalate; cellulose acetate trimellitate; cellulose acetate succinate; carboxymethyl ethylcellulose; hydroxypropyl methylcellulose acetate succinate; a mixture of sodium alginate and stearic acid; formalin treated gelatin; shellac; and mixtures thereof. Preferably each enteric coating is selected from acrylic copolymers.

Formulations for rectal administration may be presented as a suppository with a suitable base comprising, for example, cocoa butter or a salicylate, or presented as an enema with a suitable solution or gel comprising, for example, alginates, modified celluloses (such as hydroxypropyl methylcellulose), starches or poloxamers. Formulations suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams or spray formulations containing in addition to the active ingredient such carriers as are known in the art to be appropriate.

For parenteral use, the active pharmaceutical ingredients of the present invention will generally be provided in a sterile aqueous solution or suspension, buffered to an appropriate pH and isotonicity. Suitable aqueous vehicles include Ringer's solution and isotonic sodium chloride or glucose. Aqueous suspensions according to the invention may include suspending agents such as cellulose derivatives, sodium alginate, polyvinylpyrrolidone and gum tragacanth, and a wetting agent such as lecithin. Suitable preservatives for aqueous suspensions include ethyl and n-propyl p-hydroxybenzoate. The active pharmaceutical ingredients of the invention may also be presented as liposome formulations.

Suitable powders, suspensions and solutions can be used in inhalers for airway (aerosol) administration.

A sixth aspect of the present invention relates to a pharmaceutical composition or kit according to any of the preceding aspects of the present invention, for use in medicine.

In one embodiment, the pharmaceutical composition or kit of the sixth aspect of the present invention is for use in the treatment or prevention of inflammation, pain, fever, cancer or a cardiovascular disorder. In another embodiment, the pharmaceutical composition or kit of the sixth aspect of the present invention is for use in the treatment of a wound. Preferably said treatment aids wound healing. Preferably the wound is chronic, and/or has arisen from trauma, decubitis, cosmetic surgery, surgical therapy, organ or tissue transplantation, an insect bite or a burn.

A seventh aspect of the present invention relates to a method of treating or preventing inflammation, pain, fever, cancer or a cardiovascular disorder, comprising administering a therapeutically or prophylactically effective amount of a pharmaceutical composition or kit according to any of the preceding aspects of the present invention to a patient in need thereof.

In one embodiment of the sixth or seventh aspects of the present invention, the inflammation, pain, fever, cancer or cardiovascular disorder is selected from arthropathies such as rheumatoid arthritis, osteoarthritis, gout, ankylosing spondylitis, psoriatic arthritis or Reiter's syndrome; oedema; proctitis; ileus; dysmenorrhoea; metastatic bone pain; muscoskeletal disorders; backache; rheumatic and/ or muscular pain; sprains; strains; peri-articular disorders; neuralgia; headache; migraine; common cold; sore throat; postoperative pain; pain due to tissue injury such as soft tissue injury; renal colic; rheumatic fever; Kawasaki disease; colorectal cancer; pancreatic cancer; lung cancer; cancer of the upper gastrointestinal tract; myocardial infarction; cerebrovascular disease such as stroke; platelet aggregation; thrombus formation; pericarditis or coronary artery disease.

An eighth aspect of the present invention relates to a method of treating a wound comprising administering a therapeutically or prophylactically effective amount of a pharmaceutical composition or kit according to any of the preceding aspects of the present invention to a patient in need thereof. Preferably said treatment aids wound healing. Preferably the wound is chronic, and/ or has arisen from trauma, decubitis, cosmetic surgery, surgical therapy, organ or tissue transplantation, an insect bite or a burn. A ninth aspect of the present invention relates to a glycosylamine or one or more precursors thereof, or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate of said glycosylamine or precursor(s), for use in the treatment or prevention of one or more side effects associated with the administration of an anti- inflammatory or antibacterial agent, or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof.

A tenth aspect of the present invention relates to a method of treating or preventing one or more side effects associated with the administration of an anti-inflammatory or antibacterial agent, or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof, comprising administering to a patient in need thereof a therapeutically or prophylactically effective amount of a glycosylamine or one or more precursors thereof, or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate of said glycosylamine or precursor(s).

In one embodiment of the ninth or tenth aspects of the present invention, said one or more side effects are selected from:

(a) gastrointestinal disorders such as a gastrointestinal ulcer, ulcer perforation, gastrointestinal bleeding, irritable bowel syndrome, pancreatitis, dyspepsia, nausea, vomiting, diarrhoea, flatulence or other irritation of the gastrointestinal tract;

(b) pain such as abdominal pain, back pain or pain at the application site;

(c) tinnitus, headache, dizziness, confusion, agitation, vertigo, blurred vision, corneal deposits, somnolence, fatigue, insomnia, asthenia, flu-like illness or palpitations;

(d) eccymosis, hives, swelling, rash, mucosal lesions, purpura, erythema, epidermal necrolysis, vesiculo-bullous reactions, Stevens-Johnson syndrome, Reye's syndrome, hypersensitivity, photosensitivity, pruritus, pallesthesia, hypoaesthesia, oedema or angioedema;

(e) increased bleeding time, blood dyscrasias, thrombocytopenia, anaemia, jaundice or non-gastrointestinal haemorrhage such as post-surgical bleeding or cerebral bleeding; (f) cardiovascular disorders such as hypertension, vasculitis or myocardial infarction;

(g) adverse liver effects such as raised liver enzymes or hepatitis;

(h) adverse renal effects such as salt and/ or fluid retention, nephrotoxicity, raised creatinine, interstitial nephritis, allergic glomerulnonephritis, nephrotic syndrome, acute renal failure or acute tubular necrosis;

(i) urinary disorders such as urinary tract infection, oliguria, nocturia, dysuria, cystitis or haematuria; hyperkalaemia; hypokalaemia; or hypertonia; or

(j) respiratory disorders such as upper respiratory tract infection, bronchospasm, chest pain, allergic alveolitis, pulmonary eosinophilia, alveolar osteitis or pharyngitis.

In another embodiment of the ninth or tenth aspects of the present invention, said anti-inflammatory or antibacterial agent, or pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof, is as defined in relation to the first or second aspects of the present invention. Preferably said anti-inflammatory is a COX inhibitor or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof. Preferably the anti-inflammatory or antibacterial agent is for the treatment or prevention of inflammation, pain, fever, cancer or a cardiovascular disorder, such as a disorder listed in relation to the sixth or seventh aspects of the present invention. The anti-inflammatory or antibacterial agent may also be for the treatment of a wound, such as a wound listed in relation to the sixth or eighth aspects of the present invention.

In yet another embodiment of the ninth or tenth aspects of the present invention, said glycosylamine or precursor(s) thereof, or pharmaceutically acceptable tautomer, salt, prodrug or hydrate of said glycosylamine or precursor(s), is as defined in relation to the first or second aspects of the present invention, or is part of a pharmaceutical composition or kit as defined in relation to any of the preceding aspects of the present invention. In any of the sixth to tenth aspects of the present invention the subject to be treated may be a human or animal. Preferably the subject to be treated is a human.

For the avoidance of doubt, insofar as is practicable any embodiment of a given aspect of the present invention may occur in combination with any other embodiment of the same aspect of the present invention. In addition, insofar as is practicable it is to be understood that any preferred or optional embodiment of any aspect of the present invention should also be considered as a preferred or optional embodiment of any other aspect of the present invention.

Brief description of the accompanying figures

Figure 1 shows the effect of TNBS on weight loss in mice subjected to various intra-rectal treatment regimes. CD-I mice were subjected intra-rectally to TNBS and then treated either with a vehicle enema or an enema that generates a glycosylamine, and bodyweight and diarrhoea were monitored. The data are plotted as the mean with a 95% confidence interval, N=6. Weight is expressed as percentage of the starting weight (i.e. start = 100%). Figure 2 shows the effect of TNBS on weight loss in mice subjected to various intra-rectal treatment regimes. CD-I mice were subjected intra-rectally to TNBS and then treated either with a vehicle enema, an enema that generates a glycosylamine or an enema that generates a glycosylamine and comprises an antibacterial agent, and bodyweight and diarrhoea were monitored. The data are plotted as the mean with a 95% confidence interval, N=8. Weight is expressed as percentage of the starting weight (i.e. start - 100%).

Figure 3 shows the effect of monolateral CFA injection on paw thickness and the effect of treatment with a glycosylamine generating solution compared with treatment with diclofenac combined with the glycosylamine generating solution. The data are presented as the mean, N=8. Figure 4 shows the effect of monolateral CFA injection on open field mobility and the effect of treatment with a glycosylamine generating solution compared with treatment with diclofenac combined with the glycosylamine generating solution. The data are presented as the mean, N=8.

Figure 5 shows the effect of monolateral CFA injection on paw withdrawal latency and the effect of treatment with a glycosylamine generating solution compared with treatment with diclofenac combined with the glycosylamine generating solution. The data are presented as the mean, N=8.

Examples

Example 1 : Use of an enema that generates a glycosylamine to treat rectal disorders. Various rectal and proximal colon disorders may be treated with rectal enemas. Signs of disorders like proctitis may be reproduced in animals using intra-rectal insult, e.g. by the administration of an irritant like trinitrobenzenesulphonic acid (TNBS) in ethanol. In this example, female CD-I mice (N=6) were treated with either a SHAM ethanol solution or 50 mg/kg (ca. 2 mg) intra-rectal TNBS in 50% ethanol. Body weight and diarrhoea score were followed thereafter. 8 hours after receiving TNBS, the animals were randomly assigned to 3 groups: (1) vehicle (1% hydroxypropyl methylcellulose in isotonic saline); (2) 5% glucose with equimolar (NH₄)₂C0₃ in 1% hydroxypropyl methylcellulose incubated for 1 hour prior to use; or (3) 5% glucose with equimolar (NH₄)₂C0₃ in 1% hydroxypropyl methylcellulose mixed just prior to use. Treatments were applied intra-rectally, 5 ml/kg once daily.

Weight loss was monitored and the results are summarised in Figure 1. The data are plotted as the mean with a 95% confidence interval. As can be seen from Figure 1, an enema that generates a glycosylamine ameliorates the effects of the TNBS irritant.

Example 2: Use of an enema that generates a glycosylamine and optionally comprises an antibacterial agent to treat rectal disorders. Various rectal and proximal colon disorders may be treated with rectal enemas. In this example, the inventors combined in an enema an antibacterial agent, azithromycin, with a glycosylamine generating solution.

Female CD-I mice (N=8) were treated with 50 mg/kg (ca. 2 mg) intra-rectal TNBS in 50% ethanol, and body weight and diarrhoea score were followed thereafter. 8 hours after receiving TNBS, the animals were randomly assigned to 3 groups: (1) vehicle (1% hydroxypropyl methylcellulose in isotonic sahne); (2) 5% glucose with equimolar (NH₄)₂C0₃ in 1% hydroxypropyl methylcellulose; or (3) 5% glucose with equimolar (NH₄)₂C0₃ in 1% hydroxypropyl methylcellulose with 0.1 μΜ azithromycin. Treatments were applied intra-rectally, 5 ml/kg once daily. Glucose was prepared as a 10% solution in 1% hydroxypropyl methylcellulose and mixed with an equal volume of an equimolar (NH₄)₂C0₃ solution just prior to application.

Weight loss was monitored and the results are summarised in Figure 2. The data are plotted as the mean with a 95% confidence interval. As can be seen from Figure 2, an enema that comprises an antibacterial agent and generates a glycosylamine ameliorates the effects of the TNBS irritant even more than an enema that only generates a glycosylamine.

Example 3: Use of an enterically coated capsule containing a glycosylamine generating solution and optionally a NSAID to treat systemic inflammatory disease. Acute oedema is associated with many diseases and is not always a normal response to injury but rather a pathological state associated with excessive response to a local irritation (e.g. osteoarthritis). These phenomena may be reproduced in animals by the supply of a local irritant. Capsules were filled with either of the following: (1) vehicle (microcrystalline cellulose 20 μηι); (2) a mixed powder of glucose : ammonium carbonate (1.8 : 0.5); or (3) a mixed powder of glucose : ammonium carbonate : diclofenac (1.8 : 0.5 : 0.4). The capsule filling powder was weighed into a vessel in the appropriate amounts and then mixed on a ball mill to obtain a uniform mixed powder. The capsules were filled according to the directions of the manufacturer (Torpac, New Jersey) and the total filled weight was recorded. The capsules were filled according the approximate weight of the rats designated for study (ca. 195-220 g). After filling, the capsules were matched to the rats to gain as similar as possible a dose regime. Approximately 2-fold more capsules were made than required for the study. After filling, the capsules were rendered resistant to digestion in the stomach using a standard polymer coating material (Eudragit, Evonik Industries, Darmstadt) according to the manufacturer's instructions. To increase the delay in release, the inventors used a double spray coating process in which the capsules were sprayed in multiple orientations to obtain a uniform coat, allowed the capsules to dry separately, and re-sprayed the capsules. The capsules were maintained in separate containers to maintain identity.

The target dose of glucose was 100 mg/kg and the target dose of diclofenac was 10 mg/kg.

Rats (female, Wistar, ca. 200 g) were injected on the plantar surface of one paw with 20 μΐ of complete Freund's adjuvant (CFA) containing 2 mg/ml mycobacterium. The animals were monitored for paw thickness, thermal hyperalgesia and spontaneous mobility at baseline and at various times after CFA injection. The capsules were provided at -0.5, 5 and 21 hours.

Paw thickness was measured by volume. The results are summarised in Figure 3.

Spontaneous mobility was determined by placing the rat in a container on its own and monitoring movement by video recording. The video recordings were then automatically tracked using software image analysis (Stoelting, Anymaze tm) to determine the movement parameters, notably distance travelled and time in motion. Animals with a paw injury tend to minimally explore the enclosure before resting in one corner of the enclosure. Animals with this specific lesion tend to carry or drag the paw and are generally slower and less likely to move than fully healthy animals. The results are summarised in Figure 4. Thermal hyperalgesia was determined by the time required for a rat to remove its paw from a diode heat source, the time being automatically determined by a light switch. Increase in the latency time is indicative of analgesia. The results are summarised in Figure 5. As can be seen from Figures 3 to 5, the use of a glycosylamine generating solution and a NSAID together is more effective at treating inflammatory disease than the use of a glycosylamine generating solution alone.

It will be understood that the present invention has been described above by way of example only. The examples are not intended to limit the scope of the present invention. Various modifications and embodiments can be made without departing from the scope and spirit of the invention, which is defined by the following claims only.

Claims

1. A pharmaceutical composition or kit comprising:

2. A pharmaceutical composition or kit as claimed in claim 1, wherein said antiinflammatory is a COX inhibitor.

3. A pharmaceutical composition or kit as claimed in claim 2, wherein said COX inhibitor is a non-steroidal anti-inflammatory drug (NSAID).

4. A pharmaceutical composition or kit as claimed in claim 3, wherein said NSAID is selected from:

(a) an aminoarylcarboxylic acid derivative such as enfenamic acid, etofenamate, flufenamic acid, isonixin, meclofenamic acid, mefenamic acid, niflumic acid, talniflumate, terofenamate or tolfenamic acid;

(b) an arylacetic acid derivative such as aceclofenac, acemetacin, alclofenac, amfenac, amtolmetin guacil, bromfenac, bufexamac, diclofenac, etodolac, felbinac, fenclozic acid, fentiazac, glucametacin, ibufenac, indomethacin, isoxepac, lonazolac, metiazinic acid, mofezolac, nepafenac, oxametacine, proglumetacin, sulindac, tiaramide, tolmetin, tropesin or zomepirac;

(c) an arylbutyric acid derivative such as bumadizon, butibufen, butixirate or fenbufen;

(d) an arylcarboxylic acid derivative such as ketorolac or tinoridine;

(f) a pyrazole derivative such as difenamizole or epirizole; (g) ^a pyrazolone derivative such as apazone, feprazone, mofebutazone, morazone, oxyphenbutazone, phenylbutazone, pipebiazone, propyphenazone, ramiphenazone or suxibuzone;

(h) a salicylic acid derivative such as acetaminosalol, aspirin, balsalazide, benorylate, diflunisal, fendosal, gentisic acid, glycol salicylate, imidazole salicylate, lysine acetylsalicylate, mesalamine, morpholine salicylate, 1-napthyl salicylate, olsalazine, parsalmide, phenyl acetylsalicylate, phenyl salicylate, salicylamide O- acetic acid, salicylsulphuric acid, salsalate, salicylic acid or sulfasalazine;

(k) another NSAID such as ε-acetamidocaproic acid, S- adenosylmethionine, ajulemic acid, 3-amino-4-hydroxybutyric acid, bendazac, benzydamine, -bisabolol, bucolome, difenpiramide, ditazol, emorfazone, fepradinol, guaiazulene, lexipafant, hcofelone, nabumetone, nimesulide, oxaceprol, perisoxal, proquazone, superoxide dismutase or tenidap.

5. A pharmaceutical composition or kit as claimed in claim 3 or claim 4, wherein said NSAID is a salicylic acid derivative.

6. A pharmaceutical composition or kit as claimed in claim 5, wherein said salicylic acid derivative is aspirin.

7. A pharmaceutical composition or kit as claimed in claim 3 or claim 4, wherein said NSAID is an arylpropionic acid derivative.

8. A pharmaceutical composition or kit as claimed in claim 7, wherein said arylpropionic acid derivative is ibuprofen or naproxen.

9. A pharmaceutical composition or kit as claimed in claim 3 or claim 4, wherein said NSAID is a selective COX-2 inhibitor.

10. A pharmaceutical composition or kit as claimed in claim 1, wherein said antiinflammatory is a steroid.

11. A pharmaceutical composition or kit as claimed in claim 10, wherein said steroid is selected from hydrocortisone, betamethasone, cortisone, deflazacort, dexamethasone, methylprednisolone, prednisolone, triamcinolone, fludrocortisone, beclomethasone, budesonide, ciclesonide, fluticasone furoate, mometasone furoate, flunisolide, flumethasone, fluorometholone or loteprednol etabonate.

12. A pharmaceutical composition or kit as claimed in claim 1, wherein said antiinflammatory is an anti-interleukin-6 agent.

13. A pharmaceutical composition or kit as claimed in claim 12, wherein said anti-interleukin-6 agent is tocilizumab.

14. A pharmaceutical composition or kit as claimed in claim 1, wherein said antiinflammatory is a sulphated saccharide.

15. A pharmaceutical composition or kit as claimed in claim 14, wherein said sulphated saccharide is sucrose octasulphate or sucralfate.

16. A pharmaceutical composition or kit comprising:

17. A pharmaceutical composition or kit as claimed in claim 16, wherein said antibacterial agent is an antibiotic.

18. A pharmaceutical composition or kit as claimed in claim 17, wherein said antibiotic is selected from amikacin, gentamicin, neomycin, tobramycin, cefaclor, cefadroxil, cephalexin, cefixime, cefotaxime, cefpodoxime proxetil, cephradine, ceftazidime, ceftriaxone, cefuroxime, azithromycin, clarithromycin, erythromycin, erythromycin ethylsuccinate, erythromycin stearate, telithromycin, amoxicillin, ampicillin, floxacillin, penicillin G, penicillin V, piperacillin, ticarcillin, rifampin, demeclocycline, doxycycline, lymecycline, minocycline, oxytetracycline, tetracycline, aztreonam, chloramphenicol, clindamycin, colistin, daptomycin, doripenem, ertapenem, imipenem, meropenem, quinupristin, dalfopristin, fusidic acid, teicoplanin, tigecycline or vancomycin.

19. A pharmaceutical composition or kit as claimed in claim 16, wherein said antibacterial agent is a synthetic antibacterial agent.

20. A pharmaceutical composition or kit as claimed in claim 19, wherein said synthetic antibacterial agent is selected from metronidazole, tinidazole, ciprofloxacin, levofloxacin, ofloxacin, moxifloxacin, nalidixic acid, trimethoprim, sulfamethoxazole, linezolid or noxythiolin.

21. A pharmaceutical composition or kit as claimed in claim 16, wherein said antibacterial agent is a leprostatic agent, an anti-rickettsial agent or a tuberculostatic agent.

22. A pharmaceutical composition or kit as claimed in claim 16, wherein said antibacterial agent is an antibacterial adjunct.

23. A pharmaceutical composition or kit as claimed in claim 22, wherein said antibacterial adjunct is selected from clavulanic acid, tazobactam or cilastatin.

24. A pharmaceutical composition or kit as claimed in any of the preceding claims, wherein the glycosylamine comprises at least one monosaccharide subunit comprising a glycosidic -NR₂ group, a glycosidic -NR₃ ⁺ group, a directly bonded =NR group, or a directly bonded =NR₂ ⁺ group;

wherein each R is independently hydrogen, a further monosaccharide subunit, or a hydrocarbyl group, or two or three R groups and the nitrogen atom to which they are attached, together form a further monosaccharide subunit or a cyclic hydrocarbyl group;

wherein each monosaccharide subunit independently is optionally substituted and/or optionally modified; and

25. A pharmaceutical composition or kit as claimed in claim 24, wherein:

(a) one R group is not hydrogen; and/ or

(b) two R groups are not hydrogen; and/ or

(e) one R group is a hydrocarbyl group and one R group is hydrogen; and/ or

(f) two R groups are independently monosaccharide subunits; and/or

(g) two R groups are independently hydrocarbyl groups; and/ or

(h) one or two R groups are independently hydrogen, or an alkyl, acyl or alkoxycarbonyl group; and/ or

(i) one or two R groups are independently hydrogen, or a Q-Q alkyl, C₂-C₆ acyl, C₂-C₆ halo-acyl, or C^_Q alkoxycarbonyl group; and/or

(k) all R groups are hydrogen; and/ or

(1) one R group is a hydrocarbyl group or a monosaccharide subunit and one R group is an acyl group.

26. A pharmaceutical composition or kit as claimed in claim 24 or claim 25, wherein the glycosylamine comprises a sequence of at least two monosaccharide subunits directly linked by a glycosidic -NR- group, a glycosidic -NR₂ ⁺- group, a directly bonded =N- group, or a directly bonded =NR⁺- group.

27. A pharmaceutical composition or kit as claimed in claim 26, wherein the glycosidic -NR- group or the glycosidic -NR₂ ⁺- group is linked to one or both of the monosaccharide subunits by a glycosidic bond.

28. A pharmaceutical composition or kit as claimed in claim 26, wherein the directly bonded =N- group or the directly bonded =NR⁺- group is linked to one or neither of the monosaccharide subunits by a glycosidic bond.

29. A pharmaceutical composition or kit as claimed in any of claims 24 to 28, wherein the glycosylamine comprises a sequence of at least two monosaccharide subunits directly linked by a glycosidic -NR- group or a directly bonded =N- group.

30. A pharmaceutical composition or kit as claimed in any of claims 24 to 29, wherein the glycosylamine comprises at least one monosaccharide subunit comprising a glycosidic -NR₂ group or a directly bonded =NR group.

31. A pharmaceutical composition or kit as claimed in any of claims 24 to 30, wherein the glycosylamine contains 1-100, 1-20, 1 -12, 2-10, 2-8, 2-6 or 2-4 monosaccharide subunits.

32. A pharmaceutical composition or kit as claimed in any of claims 24 to 31, wherein the glycosylamine comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more monosaccharide subunits.

33. A pharmaceutical composition or kit as claimed in any of claims 24 to 32, wherein the glycosylamine contains 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 monosaccharide subunits.

34. A pharmaceutical composition or kit as claimed in any of claims 24 to 33, wherein the glycosylamine comprises a sequence of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more monosaccharide subunits.

35. A pharmaceutical composition or kit as claimed in any of claims 24 to 34, wherein the monosaccharide subunits are independently aldosyl or ketosyl monosaccharides.

36. A pharmaceutical composition or kit as claimed in claim 35, wherein 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or all monosaccharide subunits are independently triosyl, tetrosyl, pentosyl, hexosyl, heptosyl, octosyl or nonosyl monosaccharides.

37. A pharmaceutical composition or kit as claimed in claim 36, wherein 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or all monosaccharide subunits are independently glycerosyl, erythrosyl, threosyl, ribosyl, arabinosyl, xylosyl, lyxosyl, allosyl, altrosyl, glucosyl, mannosyl, gulosyl, idosyl, galactosyl, talosyl, rhamnosyl or fucosyl monosaccharides.

38. A pharmaceutical composition or kit as claimed in any of claims 24 to 37, wherein 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or all monosaccharide subunits are independently tetrosyl monosaccharides or higher, and the ring of those monosaccharides is furanosyl.

39. A pharmaceutical composition or kit as claimed in any of claims 24 to 38, wherein 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or all monosaccharide subunits are independently pentosyl monosaccharides or higher, and the ring of those monosaccharides is pyranosyl.

40. A pharmaceutical composition or kit as claimed in any of claims 24 to 39, wherein all monosaccharide subunits are independently ring-closed or open-chain or a mixture of ring-closed and open-chain.

41. A pharmaceutical composition or kit as claimed in any of claims 24 to 40, wherein one or more monosaccharide subunits are substituted and/or modified.

42. A pharmaceutical composition or kit as claimed in any of claims 24 to 41, wherein in a substituted monosaccharide subunit:

(a) independently one or more of the hydroxyl groups of the monosaccharide subunit is replaced with -H, -F, -CI, -Br, -I, -CF₃, -CC1₃, -CBr₃, -CI₃, -SH, -NH₂, -N₃, -NH=NH₂, -CN, -N0₂, -COOH, -R^a-0-R^b, -R^a-S-R^b, -R^a-SO-R^b, -R^a-S0₂-R^b, -R^a-S0₂-OR^b, -RO-S0₂-R^b, -R^a-S0₂-N(R^b)₂, -R^a-NR^b-SO_z-R^b, -R^aO-S0₂-OR^b, -R^aO-S0₂-N(R^b)₂, -R^a-NR^b-S0₂-OR^b, -R^a~NR^b-S0₂-N(R^b)₂, -R^a-N(R^b)₂, -R^a-N(R^b)₃ ⁺, -R^a-B(R^b)₂, -R^a-P(R^b)₂, -R^a-PO(R^b)₂, -R^a-Si(R^b)₃, -R^a-CO-R^b, -R^a-CO-OR^b, -R^aO-CO-R^b, -R^a-CO-N(R^b)₂, -R^a-NR^b-CO-R^b, -R^aO-CO-OR^b, -R^aO-CO-N(R^b)₂, -R^a-NR^b-CO-OR^b, -R^a-NR^b-CO-N(R^b)₂, -R^a-CS-R^b, -R^a-CS-OR^b, -R^aO-CS-R^b, -R^a-CS-N(R^b)₂, -R^a-NR^b-CS-R^b, -R^aO-CS-OR^b, -R^aO-CS-N(R^b)₂, -R^a-NR^b-CS-OR^b, -R^a-NR^b-CS-N(R^b)₂, or -R^b; and/or

(b) independently one, two or three of the hydrogens of the monosaccharide subunit is replaced with -F, -CI, -Br, -I, -CF₃, -CC1₃, -CBr₃, -CI₃, -OH, -SH, -NH₂, -N₃, -NH=NH₂, -CN, -N0₂, -COOH, -R^a-0-R^b, -R^a-S-R^b, -R^a-SO-R , -R^a-S0₂-R^b, -R^a-S0₂-OR^b, -R^aO-S0₂-R^b, -R^a-S0₂-N(R^b)₂, -R^a-NR^b-S0₂-R^b, -RO-S0₂-OR^b, -R^aO-S0₂-N(R^b)₂, -R^a-NR^b-S0₂-OR^b, -R^a-NR^b-S0₂-N(R^b)₂, -R^a-N(R^b)₂, -R^a-N(R^b)₃ ⁺, -R^a-B(R^b)₂, -R^a-P(R^b)₂, -R^a-PO(R^b)₂, -R^a-Si(R^b)₃, -R^a-CO-R^b, -R^a-CO-OR^b, -RO-CO-R^b, -R^a-CO-N(R^b)₂, -R -NR^b-CO-R^b, -RO-CO-OR^b, -R^aO-CO-N(R^b)₂, -R^a-NR^b-CO-OR^b, -R^a-NR^b-CO-N(R^b)₂, -R^a-CS-R^b, -R^a-CS-OR^b, -R^aO-CS-R^b, -R^a-CS-N(R^b)₂, -R^a-NR^b-CS-R^b, -R^aO-CS-OR^b, -RO-CS-N(R^b)₂, -R^a-NR^b-CS-OR^b, -R^a-NR^b-CS-N(R^b)₂, or -R^b; and/or

(d) independently two hydroxyl groups of the monosaccharide subunit are together replaced with -0-R^c-, -S-R^c-, -SO-R^c-, -S0₂-R^c-, or -NR -R^c-;

wherein: -R^a- is independently a chemical bond, or a substituted or unsubstituted alkylene, alkenylene or alkynylene group which optionally includes one or more heteroatoms in its carbon skeleton;

-R^b is independently hydrogen, an optionally substituted monosaccharide subunit, or a substituted or unsubstituted, straight-chain, branched or cyclic alkyl, alkenyl, alkynyl, acyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, alkylaryl, alkenylaryl or alkynylaryl group which optionally includes one or more heteroatoms in its carbon skeleton;

-R^c- is independently a chemical bond, or a substituted or unsubstituted alkylene, alkenylene or alkynylene group which optionally includes one or more heteroatoms in its carbon skeleton; and

M is a metal;

provided that the monosaccharide subunit comprises at least one -OR^b, -OSOR^b,

-OSi(R )₃, -OCOR^b, -OC0₂R , or -OM.

43. A pharmaceutical composition or kit as claimed in any of claims 24 to 42, wherein in a modified monosaccharide subunit:

(b) the ring oxygen of the modified monosaccharide subunit, or what would be the ring oxygen in the ring-closed form of the modified monosaccharide subunit, is replaced with -S- or -NR^b-, wherein -R^b is independently hydrogen, an optionally substituted monosaccharide subunit, or a substituted or unsubstituted, straight-chain, branched or cyclic alkyl, alkenyl, alkynyl, acyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, alkylaryl, alkenylaryl or alkynylaryl group which optionally includes one or more heteroatoms in its carbon skeleton.

44. A pharmaceutical composition or kit as claimed in any of claims 24 to 43, wherein each hydrocarbyl group is a substituted or unsubstituted, straight-chain, branched or cyclic alkyl, alkenyl, alkynyl, acyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, alkylaryl, alkenylaryl or alkynylaryl group which comprises 1-15 carbon atoms and optionally includes one or more heteroatoms in its carbon skeleton.

45. A pharmaceutical composition or kit as claimed in any of claims 24 to 44, wherein a substituted hydrocarbyl group is substituted with one or more of -F, -CI, -Br, -I, -CF₃, -CC1₃, -CBr₃, -CI₃, -OH, -SH, -NH₂, -N₃, -NH=NH₂, -CN, -N0₂, -COOH, -R^a-0-R^b, -R^a-S-R^b, -R^a-SO-R^b, -R^a-S0₂-R^b, -R^a-S0₂-OR^b, -R^aO-S0₂-R^b, -R^a-S0₂-N(R^b)₂, -R^a-NR^b-S0₂-R^b, -R^aO-S0₂-OR^b, -R^aO-S0₂-N(R^b)₂, -R^a-NR^b-S0₂-OR^b, -R^a-NR^b-S0₂-N(R^b)₂, -R^a-N(R^b)₂, -R^a-N(R^b)₃ ⁺, -R^a-B(R^b)₂, -R^a-P(R^b)₂, -R^a-PO(R^b)₂, -R^a-Si(R^b)₃, -R^a-CO-R^b, -R^a-CO-OR^b, -R^aO-CO-R^b, -R^a-CO-N(R^b)₂, -R^a-NR -CO-R^b, -R^aO-CO-OR^b, -R^aO-CO-N(R^b)₂, -R^a-NR^b-CO-OR^b, -R^a-NR^b-CO-N(R^b)₂, -R^a-CS-R^b, -R^a-CS-OR^b, -R^aO-CS-R^b, -R^a-CS-N(R^b)₂, -R^a-NR^b-CS-R^b, -R^aO-CS-OR^b, -R^aO-CS-N(R^b)₂, -R^a-NR^b-CS-OR^b, -R^a-NR^b-CS-N(R^b)₂, -R^b, or a monosaccharide subunit;

wherein:

-R^a- is independently a chemical bond, or a substituted or unsubstituted alkylene, alkenylene or alkynylene group which optionally includes one or more heteroatoms in its carbon skeleton; and

-R^b is independently hydrogen, an optionally substituted monosaccharide subunit, or a substituted or unsubstituted, straight-chain, branched or cyclic alkyl, alkenyl, alkynyl, acyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, alkylaryl, alkenylaryl or alkynylaryl group which optionally includes one or more heteroatoms in its carbon skeleton.

46. A pharmaceutical composition or kit as claimed in any of claims 24 to 45, wherein all monosaccharide subunits are independently in the D- or L- configuration.

47. A pharmaceutical composition or kit as claimed in any of claims 24 to 46, wherein the stereochemistry of each glycosidic bond is independently or β.

48. A pharmaceutical composition or kit as claimed in any of claims 24 to 47, wherein two R groups and the nitrogen atom to which they are attached, together do not form a heterocyclic aromatic group.

49. A pharmaceutical composition or kit as claimed in any of claims 24 to 48, wherein the glycosylamine is not a nucleoside and/or not a nucleotide.

50. A pharmaceutical composition or kit as claimed in any of claims 24 to 49, wherein the glycosylamine does not comprise a ribose subunit comprising a glycosidic tertiary amine.

51. A pharmaceutical composition or kit as claimed in any of claims 24 to 50, wherein none of the monosaccharide subunits is pyranosyl with JNT-substitution at the 2-position relative to the anomeric carbon of the pyranosyl subunit.

52. A pharmaceutical composition or kit as claimed in any of claims 24 to 51, wherein none of the monosaccharide subunits is JV-substituted a to the anomeric carbon.

53. A pharmaceutical composition or kit as claimed in any of claims 24 to 52, wherein the glycosylamine is:

(a) a glucosylamine;

(b) 1-benzamido-l -deoxy-glucose;

(c) 1 -iV-octyl-l-JV-decanoyl-l -amino- 1 -deoxy-muramyl-D-isoglutamyl- alanine;

(d) β,β-di-glucosylamine;

(e) IV-acetyl-p,P-di-glucosylamine;

(f) N-ethyl- , -di-glucosylamine; or

(g) di- (4, 4' -gluco sylgluco syl) amine .

54. A pharmaceutical composition or kit as claimed in any of claims 24 to 52, wherein the glycosylamine further comprises at least one sulphate group, wherein a sulphate group is a -0-S0₂-OR^', -NR^'-S0₂-0R , -0-S0₂-N(R^')₂ or -NR^'-S0₂-N(R')₂ group, wherein each R is independently hydrogen, a metal, a further monosaccharide subunit, or a hydrocarbyl group.

55. A pharmaceutical composition or kit as claimed in claim 54, wherein the glycosylamine comprises at least two or at least three sulphate groups.

56. A pharmaceutical composition or kit as claimed in claim 54 or claim 55, wherein the glycosylamine comprises at least one -0-S0₂-OR , -NR -S0₂-OR or

-0-S0₂-N(R^')₂ group.

57. A pharmaceutical composition or kit as claimed in claim 56, wherein the glycosylamine comprises at least one -OS0₃R group.

58. A pharmaceutical composition or kit as claimed in any of claims 54 to 57, wherein the glycosylamine comprises at least two monosaccharide subunits, each of which is substituted with at least one sulphate group.

59. A pharmaceutical composition or kit as claimed in any of claims 54 to 58, wherein 1-50, or 2-30, or 3-15, or 6-12, or all the hydroxyl groups on the monosaccharide subunits independently have been replaced with a sulphate group.

60. A pharmaceutical composition or kit as claimed in any of claims 54 to 59, wherein 1-9, or 2-8, or 3-4 hydroxyl groups on each of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,

12 or all monosaccharide subunits independently have been replaced with a sulphate group.

61. A pharmaceutical composition or kit as claimed in any of claims 54 to 60, wherein each R is independently hydrogen, a metal, or a substituted or unsubstituted, straight-chain, branched or cyclic alkyl, alkenyl, alkynyl, acyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, alkylaryl, alkenylaryl or alkynylaryl group which optionally includes one or more heteroatoms in its carbon skeleton.

62. A pharmaceutical composition or kit as claimed in claim 61, wherein each R is independently hydrogen, an alkali metal, an alkali earth metal, copper, silver, zinc, or a C_j-C^ alkyl group.

63. A pharmaceutical composition or kit as claimed in any of claims 54 to 62, wherein the glycosylamine is:

(a) a sulphated glucosylamine;

(b) l-ben2amido-l-deoxy-2,3,4,6-tetra potassium sulphonatoglucose;

(c) l-iV-octyl-l-JV-decanoyl-l-amino-l-deoxy-6-potassium sulphonate- muramyl-D-isoglutamyl-alanine;

(e) a mono-, di-, tri-, tetra-, penta-, hexa-, hepta- or octasulphated JV-acetyl- , -di-glucosylamine, or a mixture thereof;

(f) a mono-, di-, tri-, tetra-, penta-, hexa-, hepta- or octasulphated iV-ethyl- ,p-di-glucosylamine, or a mixture thereof; or

(g) a sulphated di-(4,4'-glucosylglucosyl)amine.

64. A pharmaceutical composition or kit as claimed in any of claims 1 to 23, wherein the glycosylamine has the formula (I):

wherein:

R is H, Ac, Me, Et, COCF₃, or COPh;

each R is S0₃R or H; and

each R^' is H, Li, Na or K;

or a stereoisomer thereof.

65. A pharmaceutical composition or kit as claimed in claim 64, wherein:

(a) R is Ac and all R^' are H; or

(b) R is H and all R^" are H.

66. A pharmaceutical composition or kit as claimed in any of claims 1 wherein the glycosylamine has the formula (II):

(Π)

wherein:

R is H, Ac, Me, Et, COCF₃, or COPh;

each R is S0₃R or H; and

each R^' is H, Li, Na or K;

or a stereoisomer thereof.

67. A pharmaceutical composition or kit as claimed in any of claims 1 to 23, wherein the glycosylamine has the formula (III):

wherein:

R is H, CHO or COMe;

R is S0₃R or H; and

R^' is H, Li, Na or K;

or a stereoisomer thereof.

68. A pharmaceutical composition or kit as claimed in any of claims 1 to 23, wherein the glycosylamine has the formula (IV):

wherein:

R is H, Ac, Me, Et, COCF₃, or COPh;

each R is S0₃R or H; and

each R^' is H, Li, Na or K;

or a stereoisomer thereof.

69. A pharmaceutical composition or kit as claimed in claim 68, wherein R is H or Ac and all R are H.

70. A pharmaceutical composition or kit as claimed in any of claims 1 to 23, comprising a glycosyl-precursor and/ or an amine-precursor of a glycosylamine.

71. A pharmaceutical composition or kit as claimed in claim 70, wherein the glycosyl-precursor and/or the amine-precursor is a glycosyl-precursor and/or an amine-precursor of a glycosylamine according to any of claims 24 to 69.

72. A pharmaceutical composition or kit as claimed in claim 70 or claim 71, wherein the glycosyl-precursor comprises:

(b) a directly bonded =0 group in place of a directly bonded ^NR group or a directly bonded =NR₂ ⁺ group of the glycosylamine.

73. A pharmaceutical composition or kit as claimed in any of claims 70 to 72, wherein the glycosyl-precursor is a monosaccharide, an oligosaccharide or a polysaccharide.

74. A pharmaceutical composition or kit as claimed in claim 73, wherein the glycosyl-precursor is glucose, starch, maltose, glycogen or lactose.

75. A pharmaceutical composition or kit as claimed in claim 74, wherein the glycosyl-precursor is glucose.

76. A pharmaceutical composition or kit as claimed in any of claims 70 to 75, wherein the amine-precursor is NH₃, NH₂R, NHR₂ or NR₃, wherein R is as defined in any of the preceding claims, with the proviso that R is not hydrogen.

77. A pharmaceutical composition or kit as claimed in claim 76, wherein the amine-precursor is ammonium carbonate, ammonium bicarbonate, ammonium sulphate or ammonium magnesium sulphate.

78. A pharmaceutical composition as claimed in any of claims 1 to 77, further comprising a third active pharmaceutical ingredient or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof.

79. A pharmaceutical composition as claimed in claim 78, wherein said third active pharmaceutical ingredient is an antibiotic.

80. A pharmaceutical kit comprising a pharmaceutical composition as claimed in any of claims 1 to 77, and a third active pharmaceutical ingredient or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof.

81. A pharmaceutical kit as claimed in claim 80, wherein said third active pharmaceutical ingredient is an antibiotic.

82. A pharmaceutical kit as claimed in claim 80 or claim 81, wherein said third active pharmaceutical ingredient or pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof forms part of a second pharmaceutical composition.

83. A pharmaceutical kit as claimed in any of claims 1 to 77, further comprising a third active pharmaceutical ingredient or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof.

84. A pharmaceutical kit as claimed in claim 83, wherein said third active pharmaceutical ingredient is an antibiotic.

85. A pharmaceutical kit as claimed in any of claims 1 to 77 or 80 to 84, wherein:

(a) the anti-inflammatory or antibacterial agent, or pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof forms part of a first pharmaceutical composition; and/ or

(b) the glycosylamine or precursor(s) thereof, or pharmaceutically acceptable tautomer, salt, prodrug or hydrate of said glycosylamine or precursor(s), forms part of a second pharmaceutical composition; and/or

(c) if present, the third active pharmaceutical ingredient or pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof forms part of a third pharmaceutical composition.

86. A pharmaceutical kit as claimed in claim 85, wherein:

(a) the anti-inflammatory or antibacterial agent, or pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof, and

form part of the same pharmaceutical composition.

87. A pharmaceutical kit as claimed in claim 85, wherein:

form part of the same pharmaceutical composition.

88. A pharmaceutical composition or kit as claimed in any of the preceding claims, wherein each pharmaceutical composition independently optionally comprises one or more pharmaceutically acceptable excipients.

89. A pharmaceutical composition or kit as claimed in any of the preceding claims, wherein each pharmaceutical composition is independently for oral, parenteral, transdermal, airway, rectal, vaginal or topical administration.

90. A pharmaceutical composition or kit as claimed in claim 89, wherein at least one pharmaceutical composition is for topical or transdermal administration.

91. A pharmaceutical composition or kit as claimed in claim 90, wherein each pharmaceutical composition is for topical or transdermal administration.

92. A pharmaceutical composition or kit as claimed in claim 90 or claim 91, wherein each pharmaceutical composition for topical or transdermal administration is independently in the form of an ointment, cataplasm (poultice), paste, powder, dressing, cream, plaster or patch.

93. A pharmaceutical composition or kit as claimed in claim 89, wherein at least one pharmaceutical composition is for oral administration.

94. A pharmaceutical composition or kit as claimed in claim 93, wherein each pharmaceutical composition is for oral administration.

95. A pharmaceutical composition or kit as claimed in claim 93 or claim 94, wherein each pharmaceutical composition for oral administration is independently a tablet, capsule, caplet, troche, lozenge, or is in the form of a powder, granules, an aqueous solution, suspension or dispersion.

96. A pharmaceutical composition or kit as claimed in claim 95, wherein each pharmaceutical composition for oral administration is a tablet.

97. A pharmaceutical composition or kit as claimed in any of claims 93 to 96, wherein at least one pharmaceutical composition for oral administration comprises an enteric coating.

98. A pharmaceutical composition or kit as claimed in claim 97, wherein each pharmaceutical composition for oral administration comprises an enteric coating.

99. A pharmaceutical composition or kit as claimed in claim 97 or claim 98, wherein each enteric coating is selected from acrylic copolymers such as methacrylic acid-methacrylic acid ester and methacrylic acid-acrylic acid ester copolymers; polyvinyl acetate phthalate; hydroxypropyl methylcellulose phthalate; cellulose acetate phthalate; cellulose acetate trimellitate; cellulose acetate succinate; carboxymethyl ethylcellulose; hydroxypropyl methylcellulose acetate succinate; a mixture of sodium alginate and stearic acid; formalin treated gelatin; shellac; and mixtures thereof.

100. A pharmaceutical composition or kit as claimed in claim 99, wherein each enteric coating is selected from acrylic copolymers.

101. A pharmaceutical composition or kit as claimed in any preceding claim, for use in medicine.

102. A pharmaceutical composition or kit as claimed in claim 101, for use in the treatment or prevention of inflammation, pain, fever, cancer or a cardiovascular disorder.

103. A method of treating or preventing inflammation, pain, fever, cancer or a cardiovascular disorder, comprising administering a therapeutically or prophylactically effective amount of a pharmaceutical composition or kit as claimed in any of claims 1 to 100 to a patient in need thereof.

104. A pharmaceutical composition or kit as claimed in claim 102 or a method as claimed in claim 103, wherein the inflammation, pain, fever, cancer or cardiovascular disorder is selected from arthropathies such as rheumatoid arthritis, osteoarthritis, gout, ankylosing spondylitis, psoriatic arthritis or Reiter's syndrome; oedema; proctitis; ileus; dysmenorrhoea; metastatic bone pain; muscoskeletal disorders; backache; rheumatic and/or muscular pain; sprains; strains; peri-articular disorders; neuralgia; headache; migraine; common cold; sore throat; postoperative pain; pain due to tissue injury such as soft tissue injury; renal colic; rheumatic fever; Kawasaki disease; colorectal cancer; pancreatic cancer; lung cancer; cancer of the upper gastrointestinal tract; myocardial infarction; cerebrovascular disease such as stroke; platelet aggregation; thrombus formation; pericarditis or coronary artery disease.

105. A pharmaceutical composition or kit as claimed in claim 101, for use in the treatment of a wound.

106. A method of treating a wound, comprising administering a therapeutically or prophylactically effective amount of a pharmaceutical composition or kit as claimed in any of claims 1 to 100 to a patient in need thereof.

107. A pharmaceutical composition or kit as claimed in claim 105 or a method as claimed in claim 106, wherein the wound is chronic, and/or has arisen from trauma, decubitis, cosmetic surgery, surgical therapy, organ or tissue transplantation, an insect bite or a burn.

108. A glycosylamine or one or more precursors thereof, or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate of said glycosylamine or precursor(s), for use in the treatment or prevention of one or more side effects associated with the administration of an anti-inflammatory or an antibacterial agent, or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof.

109. A method of treating or preventing one or more side effects associated with the administration of an anti-inflammatory or an antibacterial agent, or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate thereof, comprising administering to a patient in need thereof a therapeutically or prophylactically effective amount of a glycosylamine or one or more precursors thereof, or a pharmaceutically acceptable tautomer, salt, prodrug or hydrate of said glycosylamine or precursor(s).

110. A glycosylamine, precursor, tautomer, salt, prodrug or hydrate as claimed in claim 108, or a method as claimed in claim 109, wherein said one or more side effects are selected from:

(b) pain such as abdominal pain, back pain or pain at the application site; (c) tinnitus, headache, dizziness, confusion, agitation, vertigo, blurred vision, corneal deposits, somnolence, fatigue, insomnia, asthenia, flu-like illness or palpitations;

(e) increased bleeding time, blood dyscrasias, thrombocytopenia, anaemia, jaundice or non-gastrointestinal haemorrhage such as post-surgical bleeding or cerebral bleeding;

(f) cardiovascular disorders such as hypertension, vasculitis or myocardial infarction;

(g) adverse liver effects such as raised liver enzymes or hepatitis;

(h) adverse renal effects such as salt and/or fluid retention, nephrotoxicity, raised creatinine, interstitial nephritis, allergic glomerulonephritis, nephrotic syndrome, acute renal failure or acute tubular necrosis;

(i) urinary disorders such as urinary tract infection, oliguria, nocturia, dysuria, cystitis or haematuria; hyperkalaemia; hypokalemia; or hypertonia; or

111. A glycosylamine, precursor, tautomer, salt, prodrug, hydrate or method as claimed in any of claims 108 to 110, wherein said anti-inflammatory is as defined in any of claims 2 to 15.

112. A glycosylamine, precursor, tautomer, salt, prodrug, hydrate or method as claimed in any of claims 108 to 111, wherein said antibacterial agent is as defined in any of claims 17 to 23.

113. A glycosylamine, precursor, tautomer, salt, prodrug, hydrate or method as claimed in any of claims 108 to 112, wherein said glycosylamine is as defined in any of claims 24 to 69 and/ or wherein said precursor is as defined in any of claims 70 to 77.