Note: Claims are shown in the official language in which they were submitted.
What is claimed is:
1. A therapeutic kit to provide a safe and effective dosage of an antibiotic
agent, including an aerosol packaging assembly including:
a) a container accommodating a pressurized product; and
b) an outlet capable of releasing the pressurized product as a foam;
wherein the pressurized product comprises a foamable composition
comprising:
i. an antibiotic agent;
ii. at least one organic carrier selected from the group consisting of a
hydrophobic organic carrier, an organic polar solvent, an emollient
and mixtures thereof, at a concentration of about 2% to about 50%
by weight;
iii. a surface-active agent;
iv. about 0.01 % to about 5% by weight of at least one polymeric
additive selected from the group consisting of a bioadhesive agent,
a gelling agent, a film forming agent and a phase change agent;
v. water; and
vi. liquefied or compressed gas propellant at a concentration of about
3% to about 25% by weight of the total composition.
2. The kit of claim 1, wherein the foamable composition is selected from the
group consisting of an oil-in-water emulsion and a water-in-oil emulsion.
3. The kit of claim 1, wherein the outlet comprises a valve, containing a stem
with 1 to 4 apertures formed in the stem.
4. The kit of claim 3, wherein each aperture formed in the stem has a
diameter,
selected from the group consisting of (i) about 0.2 mm to about 1 mm; (ii)
about 0.3 mm to about 0.8 mm; and (iii) about 0.01 mm2 and 1 mm2.
56
5. The kit of claim 3, wherein the sum of cross-sectional areas of all
apertures in
the stem is between about 0.04 mm2 and 0.5 mm2.
6. The kit of claim 3, wherein the valve is attached to metered dose device.
7. The kit of claim 1, wherein the at least one organic carrier is present in
an
amount selected from the group consisting of (i) about 2% to about 5%; (ii)
about 5% to about 10%; (iii) about 10% to about 20%; and (iv) about 20% to
about 50% by weight.
8. The kit of claim 1, wherein the foamable composition is substantially
alcohol-
free.
9. The kit of claim 1, further including about 0.1% to about 5% by weight of a
therapeutically active foam adjuvant is selected from the group consisting of
fatty alcohols having 15 or more carbons in their carbon chain; fatty acids
having 16 or more carbons in their carbon chain; fatty alcohols derived from
beeswax and including a mixture of alcohols, a majority of which has at least
20 carbon atoms in their carbon chain; fatty alcohols having at least one
double bond; fatty acids having at least one double bond; branched fatty
alcohols; branched fatty acids; fatty acids substituted with a hydroxyl group;
cetyl alcohol; stearyl alcohol; arachidyl alcohol; behenyl alcohol; 1-
triacontanol; hexadecanoic acid; stearic acid; arachidic acid; behenic acid;
octacosanoic acid; 12-hydroxy stearic acid and mixtures thereof.
10. The kit of claim 1 or 9, wherein the antibiotic agent is selected from the
group
consisting of beta-lactam antibiotics, aminoglycosides, ansa-type antibiotics,
anthraquinones, antibiotic azoles, antibiotic glycopeptides, macrolides,
antibiotic nucleosides, antibiotic peptides, antibiotic polyenes, antibiotic
polyethers, quinolones, antibiotic steroides, sulfonamides, tetracycline,
dicarboxylic acids, antibiotic metals, oxidizing agents, substances that
release
free radicals and/or active oxygen, cationic antimicrobial agents, quaternary
57
ammonium compounds, biguanides, triguanides, bisbiguanides and analogs
and polymers thereof and naturally occurring antibiotic compounds.
11. The kit of claim 10, wherein the antibiotic agent is selected from the
group
consisting of
i. A beta-lactam, selected from the group consisting of 2-(3-
alanyl)clavam, 2-hydroxymethylclavam, 8-epi-thienamycin, acetyl-
thienamycin, amoxicillin, amoxicillin sodium, amoxicillin trihydrate,
amoxicillin-potassium clavulanate combination, ampicillin, ampicillin
sodium, ampicillin trihydrate, ampicillin-sulbactam, apalcillin,
aspoxicillin, azidocillin, azlocillin, aztreonam, bacampicillin, biapenem,
carbenicillin, carbenicillin disodium, carfecillin, carindacillin,
carpetimycin, cefacetril, cefaclor, cefadroxil, cefalexin, cefaloridine,
cefalotin, cefamandole, cefamandole, cefapirin, cefatrizine, cefatrizine
propylene glycol, cefazedone, cefazolin, cefbuperazone, cefcapene,
cefcapene pivoxil hydrochloride, cefdinir, cefditoren, cefditoren
pivoxil, cefepime, cefetamet, cefetamet pivoxil, cefixime,
cefmenoxime, cefmetazole, cefminox, cefminox, cefmolexin,
cefodizime, cefonicid, cefoperazone, ceforanide, cefoselis,
cefotaxime, cefotetan, cefotiam, cefoxitin, cefozopran, cefpiramide,
cefpirome, cefpodoxime, cefpodoxime proxetil, cefprozil, cefquinome,
cefradine, cefroxadine, cefsulodin, ceftazidime, cefteram, cefteram
pivoxil, ceftezole, ceftibuten, ceftizoxime, ceftriaxone, cefuroxime,
cefuroxime axetil, cephalosporin, cephamycin, chitinovorin, ciclacillin,
clavulanic acid, clometocillin, cloxacillin, cycloserine, deoxy
pluracidomycin, dicloxacillin, dihydro pluracidomycin, epicillin,
epithienamycin, ertapenem, faropenem, flomoxef, flucloxacillin,
hetacillin, imipenem, lenampicillin, loracarbef, mecillinam,
meropenem, metampicillin, meticillin, mezlocillin, moxalactam,
nafcillin, northienamycin, oxacillin, panipenem, penamecillin,
penicillin, phenethicillin, piperacillin, tazobactam, pivampicillin,
58
pivcefalexin, pivmecillinam, pivmecillinam hydrochloride,
pluracidomycin, propicillin, sarmoxicillin, sulbactam, sulbenicillin,
talampicillin, temocillin, terconazole, thienamycin, ticarcillin;
ii. An aminoglycosides, selected from the group consisting of 1,2'-N-DL-
isoseryl-3',4'-dideoxykanamycin B, 1,2'-N-DL-isoseryl-kanamycin B,
1,2'-N-[(S)-4-amino-2-hydroxybutyryl]-3',4'-dideoxykanamycin B, 1,2'-
N-[(S)-4-amino-2-hydroxybutyryl]-kanamycin B, 1-N-(2-
Aminobutanesulfonyl) kanamycin A, 1-N-(2-
aminoethanesulfonyl)3',4'-dideoxyribostamycin, 1-N-(2-
Aminoethanesulfonyl)3'-deoxyribostamycin, 1-N-(2-
aminoethanesulfonyl)3'4'-dideoxykanamycin B, 1-N-(2-
aminoethanesulfonyl)kanamycin A, 1-N-(2-
aminoethanesulfonyl)kanamycin B, 1-N-(2-
aminoethanesulfonyl)ribostamycin, 1-N-(2-aminopropanesulfonyl)3'-
deoxykanamycin B, 1-N-(2-aminopropanesulfonyl)3'4'-
dideoxykanamycin B, 1-N-(2-aminopropanesulfonyl)kanamycin A, 1-
N-(2-aminopropanesulfonyl)kanamycin B, 1-N-(L-4-amino-2-hydroxy-
butyryl)2,'3'-dideoxy-2'-fluorokanamycin A, 1-N-(L-4-amino-2-hydroxy-
propionyl)2,'3'-dideoxy-2'-fluorokanamycin A, 1-N-DL-3',4'-dideoxy-
isoserylkanamycin B,1-N-DL-isoserylkanamycin, 1-N-DL-
isoserylkanamycin B, 1-N-[L-(-)-(alpha-hydroxy-gamma-
aminobutyryl)]-XK-62-2, 2',3'-dideoxy-2'-fluorokanamycin A,2-
hydroxygentamycin A3, 2-hydroxygentamycin B, 2-
hydroxygentamycin B1, 2-hydroxygentamycin JI-20A, 2-
hydroxygentamycin JI-20B, 3"-N-methyl-4"-C-methyl-3',4'-dodeoxy
kanamycin A, 3"-N-methyl-4"-C-methyl-3',4'-dodeoxy kanamycin B,
3"-N-methyl-4"-C-methyl-3',4'-dodeoxy-6'-methyl kanamycin B, 3',4'-
Dideoxy-3'-eno-ribostamycin,3',4'-dideoxyneamine,3',4'-
dideoxyribostamycin, 3'-deoxy-6'-N-methyl-kanamycin B,3'-
deoxyneamine,3'-deoxyribostamycin, 3'-oxysaccharocin,3,3'-
nepotrehalosadiamine, 3-demethoxy-2"-N-formimidoylistamycin B
59
disulfate tetrahydrate, 3-demethoxyistamycin B,3-O-demethyl-2-N-
formimidoylistamycin B, 3-O-demethylistamycin B,3-
trehalosamine,4", 6"-dideoxydibekacin, 4-N-glycyl-KA-6606VI, 5"-
Amino-3',4',5"-trideoxy-butirosin A, 6"-deoxydibekacin,6'-epifortimicin
A, 6-deoxy-neomycin (structure 6-deoxy-neomycin B),6-deoxy-
neomycin B, 6-deoxy-neomycin C, 6-deoxy-paromomycin,
acmimycin, AHB-3',4'-dideoxyribostamycin,AHB-3'-deoxykanamycin
B, AHB-3'-deoxyneamine,AHB-3'-deoxyribostamycin,AHB-4"-6"-
dideoxydibekacin, AHB-6"-deoxydibekacin,AHB-
dideoxyneamine,AHB-kanamycin B, AHB-methyl-3'-deoxykanamycin
B, amikacin, amikacin sulfate, apramycin, arbekacin, astromicin,
astromicin sulfate, bekanamycin, bluensomycin, boholmycin,
butirosin, butirosin B, catenulin, coumamidine gamma1, coumamidine
gamma2,D,L-1-N-(alpha-hydroxy-beta-aminopropionyl)-XK-62-2,
dactimicin,de-O-methyl-4-N-glycyl-KA-6606VI,de-O-methyl-KA-6606I,
de-O-methyl-KA-7038I,destomycin A, destomycin B, di-N6',O3-
demethylistamycin A, dibekacin, dibekacin sulfate,
dihydrostreptomycin, dihydrostreptomycin sulfate, epi-
formamidoylglycidylfortimicin B, epihygromycin, formimidoyl-istamycin
A, formimidoyl-istamycin B, fortimicin B, fortimicin C, fortimicin D,
fortimicin KE, fortimicin KF, fortimicin KG, fortimicin KG1
(stereoisomer KG1/KG2), fortimicin KG2 (stereoisomer KG1/KG2),
fortimicin KG3, framycetin, framycetin sulphate, gentamicin,
gentamycin sulfate, globeomycin, hybrimycin A1, hybrimycin A2,
hybrimycin B1, hybrimycin B2, hybrimycin C1, hybrimycin C2,
hydroxystreptomycin, hygromycin, hygromycin B, isepamicin,
isepamicin sulfate, istamycin, kanamycin, kanamycin sulphate,
kasugamycin, lividomycin, marcomycin, micronomicin, micronomicin
sulfate, mutamicin, myomycin, N-demethyl-7-O-demethylcelesticetin,
demethylcelesticetin, methanesulfonic acid derivative of istamycin,
nebramycin, nebramycin, neomycin, netilmicin, oligostatin,
paromomycin, quintomycin, ribostamycin, saccharocin, seldomycin,
sisomicin, sorbistin, spectinomycin, streptomycin, tobramycin,
trehalosmaine, trestatin, validamycin, verdamycin, xylostasin,
zygomycin;
iii. an ansa-type antibiotics, selected from the group consisting of 21-
hydroxy-25-demethyl-25-methylthioprotostreptovaricin, 3-
methylthiorifamycin, ansamitocin, atropisostreptovaricin, awamycin,
halomicin, maytansine, naphthomycin, rifabutin, rifamide, rifampicin,
rifamycin, rifapentine, rifaximin, rubradirin, streptovaricin,
tolypomycin;
iv. an anthraquinone, selected from the group consisting of auramycin,
cinerubin, ditrisarubicin, ditrisarubicin C, figaroic acid fragilomycin,
minomycin, rabelomycin, rudolfomycin, sulfurmycin;
v. an azole, selected from the group consisting of azanidazole,
bifonazole, butoconazol, chlormidazole, chlormidazole hydrochloride,
cloconazole, cloconazole monohydrochloride, clotrimazol,
dimetridazole, econazole, econazole nitrate, enilconazole,
fenticonazole, fenticonazole nitrate, fezatione, fluconazole,
flutrimazole, isoconazole, isoconazole nitrate, itraconazole,
ketoconazole, lanoconazole, metronidazole, metronidazole benzoate,
miconazole, miconazole nitrate, neticonazole, nimorazole, niridazole,
omoconazol, ornidazole, oxiconazole, oxiconazole nitrate,
propenidazole, secnidazol, sertaconazole, sertaconazole nitrate,
sulconazole, sulconazole nitrate, tinidazole, tioconazole, voriconazol;
vi. a glycopeptide, selected from the group consisting of acanthomycin,
actaplanin, avoparcin, balhimycin, bleomycin B (copper bleomycin),
chloroorienticin, chloropolysporin, demethylvancomycin, enduracidin,
galacardin, guanidylfungin, hachimycin, demethylvancomycin, N-
nonanoyl-teicoplanin, phleomycin, platomycin, ristocetin,
staphylocidin, talisomycin, teicoplanin, vancomycin, victomycin,
xylocandin, zorbamycin;
61
vii. a macrolide, selected from the group consisting of acetylleucomycin,
acetylkitasamycin, angolamycin, azithromycin, bafilomycin, brefeldin,
carbomycin, chalcomycin, cirramycin, clarithromycin, concanamycin,
deisovaleryl-niddamycin, demycinosyl-mycinamycin, Di-O-
methyltiacumicidin, dirithromycin, erythromycin, erythromycin
estolate, erythromycin ethyl succinate, erythromycin lactobionate,
erythromycin stearate, flurithromycin, focusin, foromacidin,
haterumalide, haterumalide, josamycin, josamycin ropionate,
juvenimycin, juvenimycin, kitasamycin, ketotiacumicin, lankavacidin,
lankavamycin, leucomycin, machecin, maridomycin, megalomicin,
methylleucomycin, methymycin, midecamycin, miocamycin,
mycaminosyltylactone, mycinomycin, neutramycin, niddamycin,
nonactin, oleandomycin, phenylacetyldeltamycin, pamamycin,
picromycin, rokitamycin, rosaramicin, roxithromycin, sedecamycin,
shincomycin, spiramycin, swalpamycin, tacrolimus, telithromycin,
tiacumicin, tilmicosin, treponemycin, troleandomycin, tylosin,
venturicidin;
viii. a nucleoside, selected from the group consisting of amicetin,
angustmycin, azathymidine, blasticidin S, epiroprim, flucytosine,
gougerotin, mildiomycin, nikkomycin, nucleocidin, oxanosine,
oxanosine, puromycin, pyrazomycin, showdomycin, sinefungin,
sparsogenin, spicamycin, tunicamycin, uracil polyoxin, vengicide;
ix. apeptide, selected from the group consisting of actinomycin,
aculeacin, alazopeptin, amfomycin, amythiamycin, antifungal from
Zalerion arboricola, antrimycin, apid, apidaecin, aspartocin,
auromomycin, bacileucin, bacillomycin, bacillopeptin, bacitracin,
bagacidin, berninamycin, beta-alanyl-L-tyrosine, bottromycin,
capreomycin, caspofungine, cepacidine, cerexin, cilofungin, circulin,
colistin, cyclodepsipeptide, cytophagin, dactinomycin, daptomycin,
decapeptide, desoxymulundocandin, echanomycin, echinocandin B,
echinomycin, ecomycin, enniatin, etamycin, fabatin, ferrimycin,
62
ferrimycin, ficellomycin, fluoronocathiacin, fusaricidin, gardimycin,
gatavalin, globopeptin, glyphomycin, gramicidin, herbicolin, iomycin,
iturin, iyomycin, izupeptin, janiemycin, janthinocin, jolipeptin,
katanosin, killertoxin, lipopeptide antibiotic, lipopeptide from Zalerion
sp., lysobactin, lysozyme, macromomycin, magainin, melittin,
mersacidin, mikamycin, mureidomycin, mycoplanecin, mycosubtilin,
neopeptifluorin, neoviridogrisein, netropsin, nisin, nocathiacin,
nocathiacin 6-deoxyglycoside, nosiheptide, octapeptin, pacidamycin,
pentadecapeptide, peptifluorin, permetin, phytoactin, phytostreptin,
planothiocin, plusbacin, polcillin, polymyxin antibiotic complex,
polymyxin B, polymyxin B1, polymyxin F, preneocarzinostatin,
quinomycin, quinupristin-dalfopristin, safracin, salmycin, salmycin,
salmycin, sandramycin, saramycetin, siomycin, sperabillin,
sporamycin, a streptomyces compound, subtilin, teicoplanin
aglycone, telomycin, thermothiocin, thiopeptin, thiostrepton,
tridecaptin, tsushimycin, tuberactinomycin, tuberactinomycin,
tyrothricin, valinomycin, viomycin, virginiamycin, zervacin;
x. a naturally-occurring peptide that possesses an antibacterial and/or
an antifungal activity;
xi. a peptide obtained from a herbal or a vertebrate source;
xii. a polyene, selected from the group consisting of include, but are not
limited to amphotericin, amphotericin, aureofungin, ayfactin,
azalomycin, blasticidin, candicidin, candicidin methyl ester,
candimycin, candimycin methyl ester, chinopricin, filipin, flavofungin,
fradicin, hamycin, hydropricin, levorin, lucensomycin, lucknomycin,
mediocidin, mediocidin methyl ester, mepartricin, methylamphotericin,
natamycin, niphimycin, nystatin, nystatin methyl ester, oxypricin,
partricin, pentamycin, perimycin, pimaricin, primycin, proticin,
rimocidin, sistomycosin, sorangicin, trichomycin;
xiii. a polyether, selected from the group consisting of 20-deoxy-epi-
narasin, 20-deoxysalinomycin, carriomycin, dianemycin,
63
dihydrolonomycin, etheromycin, ionomycin, iso-lasalocid, lasalocid,
lenoremycin, lonomycin, lysocellin, monensin, narasin, oxolonomycin,
a polycyclic ether antibiotic, salinomycin;
xiv. a quinolone, selected from the group consisting of alkyl-
methylendioxy-4(1H)-oxocinnoline-3-carboxylic acid, alatrofloxacin,
cinoxacin, ciprofloxacin, ciprofloxacin hydrochloride, danofloxacin,
dermofongin A, enoxacin, enrofloxacin, fleroxacin, flumequine,
gatifloxacin, gemifloxacin, grepafloxacin, levofloxacin, lomefloxacin,
lomefloxacin, hydrochloride, miloxacin, moxifloxacin, nadifloxacin,
nalidixic acid, nifuroquine, norfloxacin, ofloxacin, orbifloxacin, oxolinic
acid, pazufloxacine, pefloxacin, pefloxacin mesylate, pipemidic acid,
piromidic acid, premafloxacin, rosoxacin, rufloxacin, sparfloxacin,
temafloxacin, tosufloxacin, trovafloxacin;
xv. a steroid, selected from the group consisting of aminosterol,
ascosteroside, cladosporide, dihydrofusidic acid, dehydro-
dihydrofusidic acid, dehydrofusidic acid, fusidic acid and squalamine;
xvi. asulfonamide, selected from the group consisting of chloramine,
dapsone, mafenide, phthalylsulfathiazole, succinylsulfathiazole,
sulfabenzamide, sulfacetamide, sulfachlorpyridazine, sulfadiazine,
sulfadiazine silver, sulfadicramide, sulfadimethoxine, sulfadoxine,
sulfaguanidine, sulfalene, sulfamazone, sulfamerazine,
sulfamethazine, sulfamethizole, sulfamethoxazole,
sulfamethoxypyridazine, sulfamonomethoxine, sulfamoxol,
sulfanilamide, sulfaperine, sulfaphenazol, sulfapyridine,
sulfaquinoxaline, sulfasuccinamide, sulfathiazole, sulfathiourea,
sulfatolamide, sulfatriazin, sulfisomidine, sulfisoxazole, sulfisoxazole
acetyl and sulfacarbamide;
xvii. a tetracycline, selected from the group consisting of
dihydrosteffimycin, demethyltetracycline, aclacinomycin,
akrobomycin, baumycin, bromotetracycline, cetocyclin,
chlortetracycline, clomocycline, daunorubicin, demeclocycline,
64
doxorubicin, doxorubicin hydrochloride, doxycycline, lymecyclin,
marcellomycin, meclocycline, meclocycline sulfosalicylate,
methacycline, minocycline, minocycline hydrochloride, musettamycin,
oxytetracycline, rhodirubin, rolitetracycline, rubomycin, serirubicin,
steffimycin and tetracycline;
xviii. a dicarboxylic acid, selected from the group consisting of adipic acid,
pimelic acid, suberic acid, azelaic acid, sebacic acid, 1,11-
undecanedioic acid, 1,12-dodecanedioic acid, 1,13-tridecanedioic
acid and 1,14-tetradecanedioic acid.
xix. an antibiotic metal or a metal ion, wherein the metal is selected from
the group consisting of silver, copper, zinc, mercury, tin, lead,
bismutin, cadmium, chromium and gold;
xx. a silver compound, selected from the group consisting of silver
acetate, silver benzoate, silver carbonate, silver iodate, silver iodide,
silver lactate, silver laurate, silver nitrate, silver oxide, silver
palmitate,
silver protein, and silver sulfadiazine;
xxi. an oxidizing agent or a substance that release free radicals and/or
active oxygen, selected from the group consisting of oxygen,
hydrogen peroxide, benzoyl peroxide, elemental halogen species, as
well as oxygenated halogen species, bleaching agents (e.g., sodium,
calcium or magnesium hypochloride and the like), perchlorite species,
iodine, iodate, and benzoyl peroxide;
xxii. a cationic antimicrobial agent, selected from the group consisting of
quaternary ammonium compounds, alkyltrimethyl ammonium
bromide, cetrimide, benzalkonium chloride, n-alkyldimethylbenzyl
ammonium chloride, dialkylmethyl ammonium halide and
dialkylbenzyl ammonium halide;
xxiii. a biguanide, a biguanidine or a triguanide having a skeleton selected
from:
Image
xxiv. a compound, selected from the group consisting of chlorhexidine
acetate, chlorhexidine gluconate and chlorhexidine hydrochloride,
picloxydine, alexidine, polihexanide, chlorproguanil hydrochloride,
proguanil hydrochloride, metformin hydrochloride, phenformin and
buformin hydrochloride;
xxv. a cationic polymeric antimicrobial agent;
xxvi. a polymeric biguanide;
xxvii. an agent, selected from the group consisting of, abomycin,
acetomycin, acetoxycycloheximide, acetylnanaomycin, an
actinoplanes sp. Compound, actinopyrone, aflastatin, albacarcin,
albacarcin, albofungin, albofungin, alisamycin, alpha-R,S-
methoxycarbonylbenzylmonate, altromycin, amicetin, amycin, amycin
demanoyl compound, amycine, amycomycin, anandimycin,
anisomycin, anthramycin, anti-syphilis imune substance, anti-
tuberculosis imune substance, antibiotic from Eschericia coli,
antibiotics from Streptomyces refuineus, anticapsin, antimycin,
aplasmomycin, aranorosin, aranorosinol, arugomycin, ascofuranone,
ascomycin, ascosin, Aspergillus flavus antibiotic, asukamycin,
aurantinin, an Aureolic acid antibiotic substance, aurodox, avilamycin,
azidamfenicol, azidimycin, bacillaene, a Bacillus larvae antibiotic,
bactobolin, benanomycin, benzanthrin, benzylmonate, bicozamycin,
bravomicin, brodimoprim, butalactin, calcimycin, calvatic acid,
candiplanecin, carumonam, carzinophilin, celesticetin, cepacin,
cerulenin, cervinomycin, chartreusin, chloramphenicol,
chloramphenicol palmitate, chloramphenicol succinate sodium,
66
chlorflavonin, chlorobiocin, chlorocarcin, chromomycin, ciclopirox,
ciclopirox olamine, citreamicin, cladosporin, clazamycin, clecarmycin,
clindamycin, coliformin, collinomycin, copiamycin, corallopyronin,
corynecandin, coumermycin, culpin, cuprimyxin, cyclamidomycin,
cycloheximide, dactylomycin, danomycin, danubomycin,
delaminomycin, demethoxyrapamycin, demethylscytophycin,
dermadin, desdamethine, dexylosyl-benanomycin, pseudoaglycone,
dihydromocimycin, dihydronancimycin, diumycin, dnacin, dorrigocin,
dynemycin, dynemycin triacetate, ecteinascidin, efrotomycin,
endomycin, ensanchomycin, equisetin, ericamycin, esperamicin,
ethylmonate, everninomicin, feldamycin, flambamycin, flavensomycin,
florfenicol, fluvomycin, fosfomycin, fosfonochlorin, fredericamycin,
frenolicin, fumagillin, fumifungin, funginon, fusacandin, fusafungin,
gelbecidine, glidobactin, grahamimycin, granaticin, griseofulvin,
griseoviridin, grisonomycin, hayumicin, hayumicin, hazymicin,
hedamycin, heneicomycin, heptelicid acid, holomycin, humidin,
isohematinic acid, karnatakin, kazusamycin, kristenin, L-
dihydrophenylalanine, a L-isoleucyl-L-2-amino-4-(4'-amino-2', 5'-
cyclohexadienyl) derivative, lanomycin, leinamycin, leptomycin,
libanomycin, lincomycin, lomofungin, lysolipin, magnesidin,
manumycin, melanomycin, methoxycarbonylmethylmonate,
methoxycarbonylethylmonate, methoxycarbonylphenylmonate,
methyl pseudomonate, methylmonate, microcin, mitomalcin,
mocimycin, moenomycin, monoacetyl cladosporin, monomethyl
cladosporin, mupirocin, mupirocin calcium, mycobacidin, myriocin,
myxopyronin, pseudoaglycone, nanaomycin, nancimycin, nargenicin,
neocarcinostatin, neoenactin, neothramycin, nifurtoinol, nocardicin,
nogalamycin, novobiocin, octylmonate, olivomycin, orthosomycin,
oudemansin, oxirapentyn, oxoglaucine methiodide, pactacin,
pactamycin, papulacandin, paulomycin, phaeoramularia fungicide,
phenelfamycin, phenyl, cerulenin, phenylmonate, pholipomycin,
67
pirlimycin, pleuromutilin, a polylactone derivative, polynitroxin,
polyoxin, porfiromycin, pradimicin, prenomycin, Prop-2-enylmonate,
protomycin, Pseudomonas antibiotic, pseudomonic acid,
purpuromycin, pyrinodemin, pyrroinitrin, pyrrolomycin, amino, chloro
pentenedioic acid, rapamycin,rebeccamycin, resistomycin, reuterin,
reveromycin, rhizocticin, roridin, rubiflavin, naphthyridinomycin,
saframycin, saphenamycin, sarkomycin, sarkomycin, sclopularin,
selenomycin, siccanin, spartanamicin, spectinomycin, spongistatin,
stravidin, streptolydigin, streptomyces arenae antibiotic complex,
streptonigrin, streptothricins, streptovitacin, streptozotocine, a
strobilurin derivative, stubomycin, sulfamethoxazol-trimethoprim,
sakamycin, tejeramycin, terpentecin, tetrocarcin, thermorubin,
thermozymocidin, thiamphenicol, thioaurin, thiolutin, thiomarinol,
thiomarinol, tirandamycin, tolytoxin, trichodermin, trienomycin,
trimethoprim, trioxacarcin, tyrissamycin, umbrinomycin,
unphenelfamycin, urauchimycin, usnic acid, uredolysin, variotin,
vermisporin, verrucarin and analogs, salts and derivatives thereof.
xxviii. a naturally occurring antibiotic compound, selected from the group
consisting of phenol, resorcinol, antibiotic aminoglycosides,
anamycin, quinines, anthraquinones, antibiotic glycopeptides, azoles,
macrolides, avilamycin, agropyrene, cnicin, aucubin antibioticsaponin
fractions, berberine (isoquinoline alkaloid), arctiopicrin
(sesquiterpene lactone), lupulone, humulone (bitter acids), allicin,
hyperforin, echinacoside, coniosetin, tetramic acid, imanine and
novoimanine;
xxix. a plant oil or extracts which contain antibiotic agents;
xxx. an oil or extract of a plant selected from the group consisting of
thyme, perilla, lavender, tea tree, terfezia claveryi, Micromonospora,
putterlickia verrucosa, putterlickia pyracantha putterlickia
retrospinosa, Maytenus ilicifolia, maytenus evonymoides, maytenus
aquifolia, faenia interjecta, cordyceps sinensis, couchgrass, holy
68
thistle, plantain, burdock, hops, echinacea, buchu, chaparral, myrrh,
red clover and yellow dock, garlic and St. John's wort; and
esters and salts thereof.
12. The kit of claim 1 or 9, wherein the concentration range of the antibiotic
agent
is selected from the group of (i) between about 0.005% and about 0.5%; (ii)
between about 0.5% and about 2%; (iii) between about 2% and about 5%;
and (iv) between about 5% and about 12%.
13. The kit of claim 1 or 9, wherein the antibiotic agent is a vasodilator.
14. The kit of claim 1 or 9, wherein upon release from the container, a shear-
sensitive foam, having a density range selected from (1) between about 0.02
gr/mL and about 0.1 gr/mL; and (2) between about 0.02 gr/mL and about 0.1
gr/mL, is produced.
15. The kit of claim 2, wherein the graded of solubility of the antibiotic
agent in the
aqueous phase of the emulsion is selected from the groups consisting of:
(i) less than 1 parts of solvent required for 1 part of solute;
(ii) from 1 to 10 parts of solvent required for 1 part of solute;
(iii) from 10 to 30 parts of solvent required for 1 part of solute;
(iv) from 30 to 100 parts of solvent required for 1 part of solute;
(v) from 100 to 1000 parts of a solvent required for 1 part of solute; and
(vi) 10,000 parts or more of a solvent required for 1 part of solute.
16. The kit of claim 2, wherein the antibiotic agent is dissolved in at least
one
phase of the emulsion.
17. The kit of claim 1, wherein the foamable composition further contains at
least
one additional therapeutic agent selected from the group consisting of an a
69
steroidal anti-inflammatory agent, an immunosuppressive agent, an
immunomodulator, an immunoregulating agent, a hormonal agent, an
antifungal agent, an antiviral agent, an antiparasitic agent, vitamin A, a
vitamin
A derivative, vitamin B, a vitamin B derivative, vitamin C, a vitamin C
derivative, vitamin D, a vitamin D derivative, vitamin E, a vitamin E
derivative,
vitamin F, a vitamin F derivative, vitamin K, a vitamin K derivative, a wound
healing agent, a disinfectant, an anesthetic, an antiallergic agent, an alpha
hydroxyl acid, lactic acid, glycolic acid, a beta-hydroxy acid, a protein, a
peptide, a neuropeptide, a allergen, an immunogenic substance, a haptene,
an oxidizing agent, an antioxidant, a dicarboxylic acid, azelaic acid, sebacic
acid, adipic acid, fumaric acid, a retinoid, an antiproliferative agent, an
anticancer agent, a photodynamic therapy agent, benzoyl chloride, calcium
hypochlorite, magnesium hypochlorite, an anti-wrinkle agent, a radical
scavenger, a metal, silver, a metal oxide, titanium dioxide, zinc oxide,
zirconium oxide, iron oxide, silicone oxide, talc, carbon, an anti wrinkle
agent,
a skin whitening agent, a skin protective agent, a masking agent, an anti-wart
agent, a refatting agent, a lubricating agent and mixtures thereof.
18. The kit of claim 1, wherein the concentration of the surface active agent
is
between about 0.1% and about 5%.
19. The kit of claim 1, wherein the surface active agent includes a mixture of
at
least one non-ionic surfactant and at least one ionic surfactant in a ratio in
the
range of about 100:1 to 1:1.
20. The kit of claim 1, wherein the surface active agent comprises a
combination
of a non-ionic surfactant and an ionic surfactant, at a ratio of between 1:1
and
20:1.
21. The kit of claim 1, wherein the surface active agent consists essentially
of a
non-ionic surfactant.
22. The kit of claim 2, wherein the emulsion is selected from:
i. an oil-in-water emulsion and wherein the HLB range of the surface
active agent is between about 9 and about 14; and
ii. a water-in-oil emulsion and wherein the HLB range of the surface
active agent is between about 2 and about 9.
23. The kit of claim 1, wherein the surface active agent comprises a
combination
of at least one non-ionic surfactant having HLB of less than 9 and at least
one
non-ionic surfactant having HLB of equal or more than 9, wherein the ratio
between the at least one non-ionic surfactant having HLB of less than 9 and
the at least one non-ionic surfactant having HLB of equal or more than 9, is
between 1:8 and 8:1.
24. The kit of claim 1, wherein the polymeric agent is selected from the group
consisting of a water-soluble polymer, a water-insoluble polymer, a gelling
agent, an inorganic gelling agent, a mucoadhesive macromolecule and a film
forming polymer.
25. The kit of claim 24, wherein the water-soluble polymer is selected from
the
group consisting of methylcellulose, hydroxypropyl cellulose, hydroxypropyl
methylcellulose (Methocel), hydroxyethyl cellulose,
methylhydroxyethylcellulose, methylhydroxypropylcellulose,
hydroxyethylcarboxymethylcellulose, carboxymethylcellulose,
carboxymethylhydroxyethylcellulose, xanthan gum, guar gum, carrageenin
gum, locust bean gum and tragacanth gum.
26. The kit of claim 1, wherein the foamable composition contains at least one
therapeutically active oil.
27. The kit of claim 1 or 9, wherein the composition further contains a
penetration
enhancer.
28. The kit of claim 27, wherein the penetration enhancer is selected from the
group consisting of propylene glycol, butylene glycols, hexylene glycol,
glycerol, pentaerythritol, sorbitol, mannitol, oligosaccharides, dimethyl
71
isosorbide, monooleate of ethoxylated glycerides having about 8 to 10
ethylene oxide units, polyethylene glycol 200-600, transcutol, glycofurol and
cyclodextrins.
29. The kit of claim 1, wherein the pH of the foamable composition is selected
from the group consisting of (i) between about 4.5 and about 7.0, wherein the
composition is intended for skin treatment; and (ii) between about 3 and about
4.5, wherein the composition is intended for vaginal treatment.
30. The kit of claim 29, wherein pH of the composition is adjusted using an
agent,
selected from the group consisting of an acid, a base and a buffering agent.
31. The kit of claim 1, wherein the organic carrier contains a PPG alkyl
ether.
32. The kit of claim 31, wherein the concentration of the PPG alkyl ether is
between about 1% and about 20%.
33. The kit of claim 32, wherein the foam is non-flammable, when tested
according to European Standard prEN 14851.
34. A therapeutic foamable composition including:
i. an antibiotic agent;
ii. a therapeutically active oil;
iii. a surface-active agent;
iv. about 0.01% to about 5% by weight of at least one polymeric
additive selected from the group consisting of a bioadhesive agent,
a gelling agent, a film forming agent and a phase change agent;
v. water; and
vi. liquefied or compressed gas propellant at a concentration of about
3% to about 25% by weight of the total composition.
35. The composition of claim 34, further including about 0.1% to about 5% by
weight of a therapeutically active foam adjuvant is selected from the group
consisting of fatty alcohols having 15 or more carbons in their carbon chain;
72
fatty acids having 16 or more carbons in their carbon chain; fatty alcohols
derived from beeswax and including a mixture of alcohols, a majority of which
has at least 20 carbon atoms in their carbon chain; fatty alcohols having at
least one double bond; fatty acids having at least one double bond; branched
fatty alcohols; branched fatty acids; fatty acids substituted with a hydroxyl
group; cetyl alcohol; stearyl alcohol; arachidyl alcohol; behenyl alcohol; 1-
triacontanol; hexadecanoic acid; stearic acid; arachidic acid; behenic acid;
octacosanoic acid; 12-hydroxy stearic acid and mixtures thereof.
36. The composition of claim 34, wherein the concentration of the surface
active
agent is between about 0.1% and about 5% by weight.
37. The composition of claim 34 or 35, wherein the antibiotic agent is
selected
from the group consisting of beta-lactam antibiotics, aminoglycosides, ansa-
type antibiotics, anthraquinones, antibiotic azoles, antibiotic glycopeptides,
macrolides, antibiotic nucleosides, antibiotic peptides, antibiotic polyenes,
antibiotic polyethers, quinolones, antibiotic steroides, sulfonamides,
tetracycline, dicarboxylic acids, antibiotic metals, oxidizing agents,
substances
that release free radicals and/or active oxygen, cationic antimicrobial
agents,
quaternary ammonium compounds, biguanides, triguanides, bisbiguanides
and analogs and polymers thereof and naturally occurring antibiotic
compounds.
38. The composition of claim 37, wherein the antibiotic agent is selected from
the
group consisting of
i. A beta-lactam, selected from the group consisting of 2-(3-
alanyl)clavam, 2-hydroxymethylclavam, 8-epi-thienamycin, acetyl-
thienamycin, amoxicillin, amoxicillin sodium, amoxicillin trihydrate,
amoxicillin-potassium clavulanate combination, ampicillin, ampicillin
sodium, ampicillin trihydrate, ampicillin-sulbactam, apalcillin,
aspoxicillin, azidocillin, azlocillin, aztreonam, bacampicillin, biapenem,
carbenicillin, carbenicillin disodium, carfecillin, carindacillin,
73
carpetimycin, cefacetril, cefaclor, cefadroxil, cefalexin, cefaloridine,
cefalotin, cefamandole, cefamandole, cefapirin, cefatrizine, cefatrizine
propylene glycol, cefazedone, cefazolin, cefbuperazone, cefcapene,
cefcapene pivoxil hydrochloride, cefdinir, cefditoren, cefditoren
pivoxil, cefepime, cefetamet, cefetamet pivoxil, cefixime,
cefmenoxime, cefmetazole, cefminox, cefminox, cefmolexin,
cefodizime, cefonicid, cefoperazone, ceforanide, cefoselis,
cefotaxime, cefotetan, cefotiam, cefoxitin, cefozopran, cefpiramide,
cefpirome, cefpodoxime, cefpodoxime proxetil, cefprozil, cefquinome,
cefradine, cefroxadine, cefsulodin, ceftazidime, cefteram, cefteram
pivoxil, ceftezole, ceftibuten, ceftizoxime, ceftriaxone, cefuroxime,
cefuroxime axetil, cephalosporin, cephamycin, chitinovorin, ciclacillin,
clavulanic acid, clometocillin, cloxacillin, cycloserine, deoxy
pluracidomycin, dicloxacillin, dihydro pluracidomycin, epicillin,
epithienamycin, ertapenem, faropenem, flomoxef, flucloxacillin,
hetacillin, imipenem, lenampicillin, loracarbef, mecillinam,
meropenem, metampicillin, meticillin, mezlocillin, moxalactam,
nafcillin, northienamycin, oxacillin, panipenem, penamecillin,
penicillin, phenethicillin, piperacillin, tazobactam, pivampicillin,
pivcefalexin, pivmecillinam, pivmecillinam hydrochloride,
pluracidomycin, propicillin, sarmoxicillin, sulbactam, sulbenicillin,
talampicillin, temocillin, terconazole, thienamycin, ticarcillin;
ii. An aminoglycosides, selected from the group consisting of 1,2'-N-DL-
isoseryl-3',4'-dideoxykanamycin B, 1,2'-N-DL-isoseryl-kanamycin B,
1,2'-N-[(S)-4-amino-2-hydroxybutyryl]-3',4'-dideoxykanamycin B, 1,2'-
N-[(S)-4-amino-2-hydroxybutyryl]-kanamycin B, 1-N-(2-
Aminobutanesulfonyl) kanamycin A, 1-N-(2-
aminoethanesulfonyl)3',4'-dideoxyribostamycin, 1-N-(2-
Aminoethanesulfonyl)3'-deoxyribostamycin, 1-N-(2-
aminoethanesulfonyl)3'4'-dideoxykanamycin B, 1-N-(2-
aminoethanesulfonyl)kanamycin A, 1-N-(2-
74
aminoethanesulfonyl)kanamycin B, 1-N-(2-
aminoethanesulfonyl)ribostamycin, 1-N-(2-aminopropanesulfonyl)3'-
deoxykanamycin B, 1-N-(2-aminopropanesulfonyl)3'4'-
dideoxykanamycin B, 1-N-(2-aminopropanesulfonyl)kanamycin A, 1-
N-(2-aminopropanesulfonyl)kanamycin B, 1-N-(L-4-amino-2-hydroxy-
butyryl)2,'3'-dideoxy-2'-fluorokanamycin A, 1-N-(L-4-amino-2-hydroxy-
propionyl)2,'3'-dideoxy-2'-fluorokanamycin A, 1-N-DL-3',4'-dideoxy-
isoserylkanamycin B,1-N-DL-isoserylkanamycin, 1-N-DL-
isoserylkanamycin B, 1-N-[L-(-)-(alpha-hydroxy-gamma-
aminobutyryl)]-XK-62-2, 2',3'-dideoxy-2'-fluorokanamycin A,2-
hydroxygentamycin A3, 2-hydroxygentamycin B, 2-
hydroxygentamycin B1, 2-hydroxygentamycin JI-20A, 2-
hydroxygentamycin JI-20B, 3"-N-methyl-4"-C-methyl-3',4'-dodeoxy
kanamycin A, 3"-N-methyl-4"-C-methyl-3',4'-dodeoxy kanamycin B,
3"-N-methyl-4"-C-methyl-3',4'-dodeoxy-6'-methyl kanamycin B, 3',4'-
Dideoxy-3'-eno-ribostamycin,3',4'-dideoxyneamine,3',4'-
dideoxyribostamycin, 3'-deoxy-6'-N-methyl-kanamycin B,3'-
deoxyneamine,3'-deoxyribostamycin, 3'-oxysaccharocin,3,3'-
nepotrehalosadiamine, 3-demethoxy-2"-N-formimidoylistamycin B
disulfate tetrahydrate, 3-demethoxyistamycin B,3-O-demethyl-2-N-
formimidoylistamycin B, 3-O-demethylistamycin B,3-
trehalosamine,4",6"-dideoxydibekacin, 4-N-glycyl-KA-6606VI, 5"-
Amino-3',4',5"-trideoxy-butirosin A, 6"-deoxydibekacin,6'-epifortimicin
A, 6-deoxy-neomycin (structure 6-deoxy-neomycin B),6-deoxy-
neomycin B, 6-deoxy-neomycin C, 6-deoxy-paromomycin,
acmimycin, AHB-3',4'-dideoxyribostamycin,AHB-3'-deoxykanamycin
B, AHB-3'-deoxyneamine,AHB-3'-deoxyribostamycin,AHB-4"-6"-
dideoxydibekacin, AHB-6"-deoxydibekacin,AHB-
dideoxyneamine,AHB-kanamycin B, AHB-methyl-3'-deoxykanamycin
B, amikacin, amikacin sulfate, apramycin, arbekacin, astromicin,
astromicin sulfate, bekanamycin, biuensomycin, boholmycin,
butirosin, butirosin B, catenulin, coumamidine gamma1, coumamidine
gamma2,D, L-1-N-(alpha-hydroxy-beta-aminopropionyl)-XK-62-2,
dactimicin,de-O-methyl-4-N-glycyl-KA-6606VI,de-O-methyl-KA-66061,
de-O-methyl-KA-70381,destomycin A, destomycin B, di-N6',O3-
demethylistamycin A, dibekacin, dibekacin sulfate,
dihydrostreptomycin, dihydrostreptomycin sulfate, epi-
formamidoylglycidylfortimicin B, epihygromycin, formimidoyl-istamycin
A, formimidoyl-istamycin B, fortimicin B, fortimicin C, fortimicin D,
fortimicin KE, fortimicin KF, fortimicin KG, fortimicin KG1
(stereoisomer KG1/KG2), fortimicin KG2 (stereoisomer KG1/KG2),
fortimicin KG3, framycetin, framycetin sulphate, gentamicin,
gentamycin sulfate, globeomycin, hybrimycin A1, hybrimycin A2,
hybrimycin B1, hybrimycin B2, hybrimycin C1, hybrimycin C2,
hydroxystreptomycin, hygromycin, hygromycin B, isepamicin,
isepamicin sulfate, istamycin, kanamycin, kanamycin sulphate,
kasugamycin, lividomycin, marcomycin, micronomicin, micronomicin
sulfate, mutamicin, myomycin, N-demethyl-7-O-demethylcelesticetin,
demethylcelesticetin, methanesulfonic acid derivative of istamycin,
nebramycin, nebramycin, neomycin, netilmicin, oligostatin,
paromomycin, quintomycin, ribostamycin, saccharocin, seldomycin,
sisomicin, sorbistin, spectinomycin, streptomycin, tobramycin,
trehalosmaine, trestatin, validamycin, verdamycin, xylostasin,
zygomycin;
iii. an ansa-type antibiotics, selected from the group consisting of 21-
hydroxy-25-demethyl-25-methylthioprotostreptovaricin, 3-
methylthiorifamycin, ansamitocin, atropisostreptovaricin, awamycin,
halomicin, maytansine, naphthomycin, rifabutin, rifamide, rifampicin,
rifamycin, rifapentine, rifaximin, rubradirin, streptovaricin,
tolypomycin;
76
iv. an anthraquinone, selected from the group consisting of auramycin,
cinerubin, ditrisarubicin, ditrisarubicin C, figaroic acid fragilomycin,
minomycin, rabelomycin, rudolfomycin, sulfurmycin;
v. an azole, selected from the group consisting of azanidazole,
bifonazole, butoconazol, chlormidazole, chlormidazole hydrochloride,
cloconazole, cloconazole monohydrochloride, clotrimazol,
dimetridazole, econazole, econazole nitrate, enilconazole,
fenticonazole, fenticonazole nitrate, fezatione, fluconazole,
flutrimazole, isoconazole, isoconazole nitrate, itraconazole,
ketoconazole, lanoconazole, metronidazole, metronidazole benzoate,
miconazole, miconazole nitrate, neticonazole, nimorazole, niridazole,
omoconazol, ornidazole, oxiconazole, oxiconazole nitrate,
propenidazole, secnidazol, sertaconazole, sertaconazole nitrate,
sulconazole, sulconazole nitrate, tinidazole, tioconazole, voriconazol;
vi. a glycopeptide, selected from the group consisting of acanthomycin,
actaplanin, avoparcin, balhimycin, bleomycin B (copper bleomycin),
chloroorienticin, chloropolysporin, demethylvancomycin, enduracidin,
galacardin, guanidylfungin, hachimycin, demethylvancomycin, N-
nonanoyl-teicoplanin, phleomycin, platomycin, ristocetin,
staphylocidin, talisomycin, teicoplanin, vancomycin, victomycin,
xylocandin, zorbamycin;
vii. a macrolide, selected from the group consisting of acetylleucomycin,
acetylkitasamycin, angolamycin, azithromycin, bafilomycin, brefeldin,
carbomycin, chalcomycin, cirramycin, clarithromycin, concanamycin,
deisovaleryl-niddamycin, demycinosyl-mycinamycin, Di-O-
methyltiacumicidin, dirithromycin, erythromycin, erythromycin
estolate, erythromycin ethyl succinate, erythromycin lactobionate,
erythromycin stearate, flurithromycin, focusin, foromacidin,
haterumalide, haterumalide, josamycin, josamycin ropionate,
juvenimycin, juvenimycin, kitasamycin, ketotiacumicin, lankavacidin,
lankavamycin, leucomycin, machecin, maridomycin, megalomicin,
77
methylleucomycin, methymycin, midecamycin, miocamycin,
mycaminosyltylactone, mycinomycin, neutramycin, niddamycin,
nonactin, oleandomycin, phenylacetyldeltamycin, pamamycin,
picromycin, rokitamycin, rosaramicin, roxithromycin, sedecamycin,
shincomycin, spiramycin, swalpamycin, tacrolimus, telithromycin,
tiacumicin, tilmicosin, treponemycin, troleandomycin, tylosin,
venturicidin;
viii. a nucleoside, selected from the group consisting of amicetin,
angustmycin, azathymidine, blasticidin S, epiroprim, flucytosine,
gougerotin, mildiomycin, nikkomycin, nucleocidin, oxanosine,
oxanosine, puromycin, pyrazomycin, showdomycin, sinefungin,
sparsogenin, spicamycin, tunicamycin, uracil polyoxin, vengicide;
ix. apeptide, selected from the group consisting of actinomycin,
aculeacin, alazopeptin, amfomycin, amythiamycin, antifungal from
Zalerion arboricola, antrimycin, apid, apidaecin, aspartocin,
auromomycin, bacileucin, bacillomycin, bacillopeptin, bacitracin,
bagacidin, berninamycin, beta-alanyl-L-tyrosine, bottromycin,
capreomycin, caspofungine, cepacidine, cerexin, cilofungin, circulin,
colistin, cyclodepsipeptide, cytophagin, dactinomycin, daptomycin,
decapeptide, desoxymulundocandin, echanomycin, echinocandin B,
echinomycin, ecomycin, enniatin, etamycin, fabatin, ferrimycin,
ferrimycin, ficellomycin, fluoronocathiacin, fusaricidin, gardimycin,
gatavalin, globopeptin, glyphomycin, gramicidin, herbicolin, iomycin,
iturin, iyomycin, izupeptin, janiemycin, janthinocin, jolipeptin,
katanosin, killertoxin, lipopeptide antibiotic, lipopeptide from Zalerion
sp., lysobactin, lysozyme, macromomycin, magainin, melittin,
mersacidin, mikamycin, mureidomycin, mycoplanecin, mycosubtilin,
neopeptifluorin, neoviridogrisein, netropsin, nisin, nocathiacin,
nocathiacin 6-deoxyglycoside, nosiheptide, octapeptin, pacidamycin,
pentadecapeptide, peptifluorin, permetin, phytoactin, phytostreptin,
planothiocin, plusbacin, polcillin, polymyxin antibiotic complex,
78
polymyxin B, polymyxin B1, polymyxin F, preneocarzinostatin,
quinomycin, quinupristin-dalfopristin, safracin, salmycin, salmycin,
salmycin, sandramycin, saramycetin, siomycin, sperabillin,
sporamycin, a streptomyces compound, subtilin, teicoplanin
aglycone, telomycin, thermothiocin, thiopeptin, thiostrepton,
tridecaptin, tsushimycin, tuberactinomycin, tuberactinomycin,
tyrothricin, valinomycin, viomycin, virginiamycin, zervacin;
X. a naturally-occurring peptide that possesses an antibacterial and/or
an antifungal activity;
xi. a peptide obtained from a herbal or a vertebrate source;
xii. a polyene, selected from the group consisting of include, but are not
limited to amphotericin, amphotericin, aureofungin, ayfactin,
azalomycin, blasticidin, candicidin, candicidin methyl ester,
candimycin, candimycin methyl ester, chinopricin, filipin, flavofungin,
fradicin, hamycin, hydropricin, levorin, lucensomycin, lucknomycin,
mediocidin, mediocidin methyl ester, mepartricin, methylamphotericin,
natamycin, niphimycin, nystatin, nystatin methyl ester, oxypricin,
partricin, pentamycin, perimycin, pimaricin, primycin, proticin,
rimocidin, sistomycosin, sorangicin, trichomycin;
xiii. a polyether, selected from the group consisting of 20-deoxy-epi-
narasin, 20-deoxysalinomycin, carriomycin, dianemycin,
dihydrolonomycin, etheromycin, ionomycin, iso-lasalocid, lasalocid,
lenoremycin, lonomycin, lysocellin, monensin, narasin, oxolonomycin,
a polycyclic ether antibiotic, salinomycin;
xiv. a quinolone, selected from the group consisting of alkyl-
methylendioxy-4(1H)-oxocinnoline-3-carboxylic acid, alatrofloxacin,
cinoxacin, ciprofloxacin, ciprofloxacin hydrochloride, danofloxacin,
dermofongin A, enoxacin, enrofloxacin, fleroxacin, flumequine,
gatifloxacin, gemifloxacin, grepafloxacin, levofloxacin, lomefloxacin,
lomefloxacin, hydrochloride, miloxacin, moxifloxacin, nadifloxacin,
nalidixic acid, nifuroquine, norfloxacin, ofloxacin, orbifloxacin, oxolinic
79
acid, pazufloxacine, pefloxacin, pefloxacin mesylate, pipemidic acid,
piromidic acid, premafloxacin, rosoxacin, rufloxacin, sparfloxacin,
temafloxacin, tosufloxacin, trovafloxacin;
xv. a steroid, selected from the group consisting of aminosterol,
ascosteroside, cladosporide, dihydrofusidic acid, dehydro-
dihydrofusidic acid, dehydrofusidic acid, fusidic acid and squalamine;
xvi. asulfonamide, selected from the group consisting of chloramine,
dapsone, mafenide, phthalylsulfathiazole, succinylsulfathiazole,
sulfabenzamide, sulfacetamide, sulfachlorpyridazine, sulfadiazine,
sulfadiazine silver, sulfadicramide, sulfadimethoxine, sulfadoxine,
sulfaguanidine, sulfalene, sulfamazone, sulfamerazine,
sulfamethazine, sulfamethizole, sulfamethoxazole,
sulfamethoxypyridazine, sulfamonomethoxine, sulfamoxol,
sulfanilamide, sulfaperine, sulfaphenazol, sulfapyridine,
sulfaquinoxaline, sulfasuccinamide, sulfathiazole, sulfathiourea,
sulfatolamide, sulfatriazin, sulfisomidine, sulfisoxazole, sulfisoxazole
acetyl and sulfacarbamide;
xvii. a tetracycline, selected from the group consisting of
dihydrosteffimycin, demethyltetracycline, aclacinomycin,
akrobomycin, baumycin, bromotetracycline, cetocyclin,
chlortetracycline, clomocycline, daunorubicin, demeclocycline,
doxorubicin, doxorubicin hydrochloride, doxycycline, lymecyclin,
marcellomycin, meclocycline, meclocycline sulfosalicylate,
methacycline, minocycline, minocycline hydrochloride, musettamycin,
oxytetracycline, rhodirubin, rolitetracycline, rubomycin, serirubicin,
steffimycin and tetracycline;
xviii. a dicarboxylic acid, selected from the group consisting of adipic acid,
pimelic acid, suberic acid, azelaic acid, sebacic acid, 1,11 -
undecanedioic acid, 1, 1 2-dodecanedioic acid, 1, 1 3-tridecanedioic
acid and 1, 1 4-tetradecanedioic acid.
80
xix. an antibiotic metal or a metal ion, wherein the metal is selected from
the group consisting of silver, copper, zinc, mercury, tin, lead,
bismutin, cadmium, chromium and gold;
xx. a silver compound, selected from the group consisting of silver
acetate, silver benzoate, silver carbonate, silver iodate, silver iodide,
silver lactate, silver laurate, silver nitrate, silver oxide, silver
palmitate,
silver protein, and silver sulfadiazine;
xxi. an oxidizing agent or a substance that release free radicals and/or
active oxygen, selected from the group consisting of oxygen,
hydrogen peroxide, benzoyl peroxide, elemental halogen species, as
well as oxygenated halogen species, bleaching agents (e.g., sodium,
calcium or magnesium hypochloride and the like), perchlorite species,
iodine, iodate, and benzoyl peroxide;
xxii. a cationic antimicrobial agent, selected from the group consisting of
quaternary ammonium compounds, alkyltrimethyl ammonium
bromide, cetrimide, benzalkonium chloride, n-alkyldimethylbenzyl
ammonium chloride, dialkylmethyl ammonium halide and
dialkylbenzyl ammonium halide;
xxiii. a biguanide, a biguanidine or a triguanide having a skeleton selected
from:
Image
xxiv. a compound, selected from the group consisting of chlorhexidine
acetate, chlorhexidine gluconate and chlorhexidine hydrochloride,
picloxydine, alexidine, polihexanide, chlorproguanil hydrochloride,
proguanil hydrochloride, metformin hydrochloride, phenformin and
buformin hydrochloride;
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xxv. a cationic polymeric antimicrobial agent;
xxvi. a polymeric biguanide;
xxvii. an agent, selected from the group consisting of, abomycin,
acetomycin, acetoxycycloheximide, acetyinanaomycin, an
actinoplanes sp. Compound, actinopyrone, aflastatin, albacarcin,
albacarcin, albofungin, albofungin, alisamycin, alpha-R,S-
methoxycarbonylbenzylmonate, altromycin, amicetin, amycin, amycin
demanoyl compound, amycine, amycomycin, anandimycin,
anisomycin, anthramycin, anti-syphilis imune substance, anti-
tuberculosis imune substance, antibiotic from Eschericia coli,
antibiotics from Streptomyces refuineus, anticapsin, antimycin,
aplasmomycin, aranorosin, aranorosinol, arugomycin, ascofuranone,
ascomycin, ascosin, Aspergillus flavus antibiotic, asukamycin,
aurantinin, an Aureolic acid antibiotic substance, aurodox, avilamycin,
azidamfenicol, azidimycin, bacillaene, a Bacillus larvae antibiotic,
bactobolin, benanomycin, benzanthrin, benzylmonate, bicozamycin,
bravomicin, brodimoprim, butalactin, calcimycin, calvatic acid,
candiplanecin, carumonam, carzinophilin, celesticetin, cepacin,
cerulenin, cervinomycin, chartreusin, chloramphenicol,
chloramphenicol palmitate, chloramphenicol succinate sodium,
chlorflavonin, chlorobiocin, chlorocarcin, chromomycin, ciclopirox,
ciclopirox olamine, citreamicin, cladosporin, clazamycin, clecarmycin,
clindamycin, coliformin, collinomycin, copiamycin, corallopyronin,
corynecandin, coumermycin, culpin, cuprimyxin, cyclamidomycin,
cycloheximide, dactylomycin, danomycin, danubomycin,
delaminomycin, demethoxyrapamycin, demethyiscytophycin,
dermadin, desdamethine, dexylosyl-benanomycin, pseudoaglycone,
dihydromocimycin, dihydronancimycin, diumycin, dnacin, dorrigocin,
dynemycin, dynemycin triacetate, ecteinascidin, efrotomycin,
endomycin, ensanchomycin, equisetin, ericamycin, esperamicin,
ethylmonate, everninomicin, feldamycin, flambamycin, flavensomycin,
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florfenicol, fluvomycin, fosfomycin, fosfonochlorin, fredericamycin,
frenolicin, fumagillin, fumifungin, funginon, fusacandin, fusafungin,
gelbecidine, glidobactin, grahamimycin, granaticin, griseofulvin,
griseoviridin, grisonomycin, hayumicin, hayumicin, hazymicin,
hedamycin, heneicomycin, heptelicid acid, holomycin, humidin,
isohematinic acid, karnatakin, kazusamycin, kristenin, L-
dihydrophenylalanine, a L-isoleucyl-L-2-amino-4-(4'-amino-2',5'-
cyclohexadienyl) derivative, lanomycin, leinamycin, leptomycin,
libanomycin, lincomycin, lomofungin, lysolipin, magnesidin,
manumycin, melanomycin, methoxycarbonylmethylmonate,
methoxycarbonylethylmonate, methoxycarbonylphenylmonate,
methyl pseudomonate, methylmonate, microcin, mitomalcin,
mocimycin, moenomycin, monoacetyl cladosporin, monomethyl
cladosporin, mupirocin, mupirocin calcium, mycobacidin, myriocin,
myxopyronin, pseudoaglycone, nanaomycin, nancimycin, nargenicin,
neocarcinostatin, neoenactin, neothramycin, nifurtoinol, nocardicin,
nogalamycin, novobiocin, octylmonate, olivomycin, orthosomycin,
oudemansin, oxirapentyn, oxoglaucine methiodide, pactacin,
pactamycin, papulacandin, paulomycin, phaeoramularia fungicide,
phenelfamycin, phenyl, cerulenin, phenylmonate, pholipomycin,
pirlimycin, pleuromutilin, a polylactone derivative, polynitroxin,
polyoxin, porfiromycin, pradimicin, prenomycin, Prop-2-enylmonate,
protomycin, Pseudomonas antibiotic, pseudomonic acid,
purpuromycin, pyrinodemin, pyrrolnitrin, pyrrolomycin, amino, chloro
pentenedioic acid, rapamycin,rebeccamycin, resistomycin, reuterin,
reveromycin, rhizocticin, roridin, rubiflavin, naphthyridinomycin,
saframycin, saphenamycin, sarkomycin, sarkomycin, sclopularin,
selenomycin, siccanin, spartanamicin, spectinomycin, spongistatin,
stravidin, streptolydigin, streptomyces arenae antibiotic complex,
streptonigrin, streptothricins, streptovitacin, streptozotocine, a
strobilurin derivative, stubomycin, sulfamethoxazol-trimethoprim,
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sakamycin, tejeramycin, terpentecin, tetrocarcin, thermorubin,
thermozymocidin, thiamphenicol, thioaurin, thiolutin, thiomarinol,
thiomarinol, tirandamycin, tolytoxin, trichodermin, trienomycin,
trimethoprim, trioxacarcin, tyrissamycin, umbrinomycin,
unphenelfamycin, urauchimycin, usnic acid, uredolysin, variotin,
vermisporin, verrucarin and analogs, salts and derivatives thereof.
xxviii. a naturally occurring antibiotic compound, selected from the group
consisting of phenol, resorcinol, antibiotic aminoglycosides,
anamycin, quinines, anthraquinones, antibiotic glycopeptides, azoles,
macrolides, avilamycin, agropyrene, cnicin, aucubin antibioticsaponin
fractions, berberine (isoquinoline alkaloid), arctiopicrin
(sesquiterpene lactone), lupulone, humulone (bitter acids), allicin,
hyperforin, echinacoside, coniosetin, tetramic acid, imanine and
novoimanine;
xxix. a plant oil or extracts which contain antibiotic agents;
xxx. an oil or extract of a plant selected from the group consisting of
thyme, perilla, lavender, tea tree, terfezia claveryi, Micromonospora,
putterlickia verrucosa , putterlickia pyracantha putterlickia
retrospinosa, Maytenus ilicifolia, maytenus evonymoides., maytenus
aquifolia, faenia interjecta, cordyceps sinensis, couchgrass, holy
thistle, plantain, burdock, hops, echinacea, buchu, chaparral, myrrh,
red clover and yellow dock, garlic and St. John's wort; and
esters and salts thereof.
39. The composition of claim 34, wherein the foamable composition further
comprises at least one additional therapeutic agent.
40.The composition of claim 39, wherein the additional therapeutic agent is
selected from the group consisting of a steroidal anti-inflammatory agent, an
immunosuppressive agent, an immunomodulator, an immunoregulating agent,
a hormonal agent, an antifungal agent, an antiviral agent, an antiparasitic
agent, vitamin A, a vitamin A derivative, vitamin B, a vitamin B derivative,
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vitamin C, a vitamin C derivative, vitamin D, a vitamin D derivative, vitamin
E,
a vitamin E derivative, vitamin F, a vitamin F derivative, vitamin K, a
vitamin K
derivative, a wound healing agent, a disinfectant, an anesthetic, an
antiallergic agent, an alpha hydroxyl acid, lactic acid, glycolic acid, a beta-
hydroxy acid, a protein, a peptide, a neuropeptide, a allergen, an
immunogenic substance, a haptene, an oxidizing agent, an antioxidant, a
dicarboxylic acid, azelaic acid, sebacic acid, adipic acid, fumaric acid, a
retinoid, an antiproliferative agent, an anticancer agent, a photodynamic
therapy agent, benzoyl chloride, calcium hypochlorite, magnesium
hypochlorite, an anti-wrinkle agent, a radical scavenger, a metal, silver, a
metal oxide, titanium dioxide, zinc oxide, zirconium oxide, iron oxide,
silicone
oxide, talc, carbon, an anti wrinkle agent, a skin whitening agent, a skin
protective agent, a masking agent, an anti-wart agent, a refatting agent, a
lubricating agent and mixtures thereof.
41.The foamable composition of claim 40, wherein the composition further
contains a penetration enhancer.
42. The foamable composition of claim 41, wherein the penetration enhancer is
selected from the group consisting of propylene glycol, butylene glycols,
hexylene glycol, glycerol, pentaerythritol, sorbitol, mannitol,
oligosaccharides,
dimethyl isosorbide, monooleate of ethoxylated glycerides having about 8 to
ethylene oxide units, polyethylene glycol 200-600, transcutol, glycofurol
and cyclodextrins.
43. The composition of claim 34, wherein the pH of the foamable composition is
selected from the group consiting of (i) between about 4.5 and about 7.0,
wherein the composition is intended for skin treatment; and (ii) between about
3 and about 4.5, wherein the composition is intended for vaginal treatment.
44. The composition of claim 43, wherein pH of the composition is adjusted
using
an agent selected from the group consisting of an acid, a base and a buffering
agent.
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45. The composition of claim 34, wherein the organic carrier contains a PPG
alkyl
ether.
46.The composition of claim 45, wherein the concentration of the PPG alkyl
ether
is between about 1% and about 20%.
47.The composition of claim 45, wherein the foam is non-flammable, when tested
according to European Standard prEN 14851.
48. The composition of claim 41, wherein the antibiotic agent is an antibiotic
azole
and wherein the penetration enhancer is selected from the group consisting of
propylene glycol, hexylene glycol, glycerol, and dimethyl isosorbide.
49. The composition of claim 42, wherein the antibiotic agent is an antibiotic
azole
and wherein the penetration enhancer is selected from the group consisting of
propylene glycol, hexylene glycol, glycerol, polyethylene glycol and dimethyl
isosorbide.
50.The composition of claim 49, wherein the antibiotic azole is metronidazole;
and wherein the concentration of metronidazole is greater than 0.75%.
51. The composition of claim 50, wherein the concentration of metronidazole is
between 0.9% and about 2%.
52. The composition of claim 42, wherein the additional therapeutic agent is a
dicarboxylic acid and wherein the penetration enhancer is selected from the
group consisting of propylene glycol, hexylene glycol, glycerol, polyethylene
glycol and dimethyl isosorbide
53.The composition of claim 34, wherein the antibiotic agent is azelaic acid;
and
wherein the concentration of azelaic acid is greater than 10%.
54. The composition of claim 53, wherein the concentration of azelaic acid is
between about 10% and about 25%.
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55. The composition of claim 39, wherein the antibiotic agent is suitable for
the
treatment of impetigo and the additional active agent is an anti-inflammatory
agent
56. The composition of claim 39, wherein the antibiotic agent is suitable for
the
treatment of chronic ulcer and the additional active agent is selected from
the
group consisting of a topical anesthetic agent, an antifungal, an anti viral
infections and a vasoactive agent.
57.The composition of claim 39, wherein the antibiotic agent is suitable for
the
treatment of acne and the additional active agent is selected from the group
consisting of a retinoid; a keratolytic acid, an alpha-hydroxy acid and
derivatives thereof, a beta-hydroxy acid and derivatives thereof, a skin-
drying
agent, a corticosteroid, a non-steroidal anti-inflammatory agent. and an anti-
seborrhea agent.
58. The composition of claim 39, wherein the antibiotic agent is suitable for
the
treatment of rosacea and the additional active agent is selected from the
group consisting of a retinoid; a keratolytic acid, an alpha-hydroxy acid, a
beta-hydroxy acid, a corticosteroid and a non-steroidal anti-inflammatory
agent.
59. The composition of claim 39, wherein the antibiotic agent is suitable for
the
treatment of otitis and the additional active agent is selected from the group
consisting of an antifungal agent, a topical anesthetic agent, a
corticosteroid
and a non-steroidal anti-inflammatory agent.
60. A method of treating, alleviating or preventing disorders of the skin,
body
cavity or mucosal surface, wherein the disorder involves inflammation as one
of its etiological factors, the method comprising:
administering topically to a subject having the disorder, a foamed composition
including:
87
(i) an antibiotic agent;
(ii) at least one organic carrier selected from a hydrophobic organic carrier,
a polar solvent, an emollient and mixtures thereof, at a concentration of
about 2% to about 50% by weight;
(iii) a surface-active agent;
(iv) about 0.01% to about 5% by weight of a polymeric additive selected from
a bioadhesive agent, a gelling agent, a film forming agent and a phase
change agent; and
(v) water,
wherein the antibiotic agent is administered in a therapeutically effective
amount.
61.The method of claim 60, wherein the concentration of the surface active
agent
is between about 0.1 % and about 5% by weight.
62. The method of claim 60, wherein the composition further comprises about
0.1 % to about 5% by weight of a therapeutically active foam adjuvant is
selected from the group consisting of fatty alcohols having 15 or more
carbons in their carbon chain; fatty acids having 16 or more carbons in their
carbon chain; fatty alcohols derived from beeswax and including a mixture of
alcohols, a majority of which has at least 20 carbon atoms in their carbon
chain; fatty alcohols having at least one double bond; fatty acids having at
least one double bond; branched fatty alcohols; branched fatty acids; fatty
acids substituted with a hydroxyl group; cetyl alcohol; stearyl alcohol;
arachidyl alcohol; behenyl alcohol; 1-triacontanol; hexadecanoic acid; stearic
acid; arachidic acid; behenic acid; octacosanoic acid; 12-hydroxy stearic acid
and mixtures thereof.
63. The composition of claim 60 or 62, wherein the antibiotic agent is
selected
from the group consisting of beta-lactam antibiotics, aminoglycosides, ansa-
type antibiotics, anthraquinones, antibiotic azoles, antibiotic glycopeptides,
macrolides, antibiotic nucleosides, antibiotic peptides, antibiotic polyenes,
antibiotic polyethers, quinolones, antibiotic steroids, sulfonamides,
88
tetracycline, dicarboxylic acids, antibiotic metals, oxidizing agents,
substances
that release free radicals and/or active oxygen, cationic antimicrobial
agents,
quaternary ammonium compounds, biguanides, triguanides, bisbiguanides
and analogs and polymers thereof and naturally occurring antibiotic
compounds.
64.The method of claim 60, wherein the disorder is selected from the group
consisting of a dermatose, a dermatitis, a vaginal disorder, a vulvar
disorder,
an anal disorder, a disorder of a body cavity, an ear disorder, a disorder of
the
nose, a disorder of the respiratory system, a bacterial infection, fungal
infection, viral infection, dermatosis, dermatitis, parasitic infections,
disorders
of hair follicles and sebaceous glands, scaling papular diseases, benign
tumors, malignant tumors, reactions to sunlight, bullous diseases,
pigmentation disorders, disorders of cornification, pressure sores, disorders
of
sweating, inflammatory reactions, xerosis, ichthyosis, allergy, burn, wound,
cut, chlamydia infection, gonorrhea infection, hepatitis B, herpes, HIV/AIDS,
human papillomavirus (HPV), genital warts, bacterial vaginosis, candidiasis,
chancroid, granuloma Inguinale, lymphogranloma venereum, mucopurulent
cervicitis (MPC), molluscum contagiosum, nongonococcal urethritis (NGU),
trichomoniasis, vulvar disorders, vulvodynia, vulvar pain, yeast infection,
vulvar dystrophy, vulvar intraepithelial neoplasia (VIN), contact dermatitis,
osteoarthritis, joint pain, hormonal disorder, pelvic inflammation,
endometritis,
salpingitis, oophoritis, genital cancer, cancer of the cervix, cancer of the
vulva,
cancer of the vagina, vaginal dryness, dyspareunia, anal and rectal disease,
anal abscess/fistula, anal cancer, anal fissure, anal warts, Crohn's disease,
hemorrhoids, anal itch, pruritus ani, fecal incontinence, constipation, polyps
of
the colon and rectum;
and wherein the disorder is responsive to treatment with the antibiotic agent.
65.The method of claim 60, wherein the composition further comprises at least
one additional therapeutic agent, selected from the group consisting of a
steroidal anti-inflammatory agent, an immunosuppressive agent, an
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immunomodulator, an immunoregulating agent, a hormonal agent, an
antifungal agent, an antiviral agent, an antiparasitic agent, vitamin A, a
vitamin
A derivative, vitamin B, a vitamin B derivative, vitamin C, a vitamin C
derivative, vitamin D, a vitamin D derivative, vitamin E, a vitamin E
derivative,
vitamin F, a vitamin F derivative, vitamin K, a vitamin K derivative, a wound
healing agent, a disinfectant, an anesthetic, an antiallergic agent, an alpha
hydroxyl acid, lactic acid, glycolic acid, a beta-hydroxy acid, a protein, a
peptide, a neuropeptide, a allergen, an immunogenic substance, a haptene,
an oxidizing agent, an antioxidant, a dicarboxylic acid, azelaic acid, sebacic
acid, adipic acid, fumaric acid, a retinoid, an antiproliferative agent, an
anticancer agent, a photodynamic therapy agent, benzoyl chloride, calcium
hypochlorite, magnesium hypochlorite, an anti-wrinkle agent, a radical
scavenger, a metal, silver, a metal oxide, titanium dioxide, zinc oxide,
zirconium oxide, iron oxide, silicone oxide, talc, carbon, an anti wrinkle
agent,
a skin whitening agent, a skin protective agent, a masking agent, an anti-wart
agent, a refatting agent, a lubricating agent and mixtures thereof.
66.The method of claim 36, wherein the composition further contains a
penetration enhancer.
67.The method of claim 41, wherein the penetration enhancer is selected from
the group consisting of propylene glycol, butylene glycols, hexylene glycol,
glycerol, pentaerythritol, sorbitol, mannitol, oligosaccharides, dimethyl
isosorbide, monooleate of ethoxylated glycerides having about 8 to 10
ethylene oxide units, polyethylene glycol 200-600, transcutol, glycofurol and
cyclodextrins.
68.The method of claim 60, wherein the pH of the foamable composition is
selected from the group consisting of (i) between about 4.5 and about 7.0,
wherein the composition is intended for skin treatment; and (ii) between about
3 and about 4.5, wherein the composition is intended for vaginal treatment.
90
69.The method of claim 60, wherein the organic carrier contains a PPG alkyl
ether.
70.The method of claim 69, wherein the foam is non-flammable, when tested
according to European Standard prEN 14851.
71.The method of claim 66, wherein the active agent is an antibiotic azole and
wherein the penetration enhancer is selected from the group consisting of
propylene glycol, hexylene glycol, glycerol, and dimethyl isosorbide.
72.The method of claim 67, wherein the antibiotic agent is an antibiotic azole
and
wherein the penetration enhancer is selected from the group consisting of
propylene glycol, hexylene glycol, glycerol, polyethylene glycol and dimethyl
isosorbide.
73.The method of claim 72, wherein the antibiotic azole is metronidazole; and
wherein the concentration of metronidazole is greater than 0.75%.
74.The method of claim 73, wherein the concentration of metronidazole is
between 0.9% and about 2%.
75.The method of claim 67, wherein the additional therapeutic agent is a
dicarboxylic acid and wherein the penetration enhancer is selected from the
group consisting of propylene glycol, hexylene glycol, glycerol, polyethylene
glycol and dimethyl isosorbide
76.The method of claim 60, wherein the antibiotic agent is azelaic acid; and
wherein the concentration of azelaic acid is greater than 10%.
77.The method of claim 76, wherein the concentration of azelaic acid is
between
about 10% and about 25%.
78.The method of claim 65, wherein the antibiotic agent is suitable for the
treatment of impetigo and the additional active agent is an anti-inflammatory
agent
91
79.The method of claim 65, wherein the antibiotic agent is suitable for the
treatment of chronic ulcer and the additional active agent is selected from
the
group consisting of a topical anesthetic agent, an antifungal, an anti viral
infections and a vasoactive agent.
80.The method of claim 65, wherein the antibiotic agent is suitable for the
treatment of acne and the additional active agent is selected from the group
consisting of a retinoid; a keratolytic acid, an alpha-hydroxy acid and
derivatives thereof, a beta-hydroxy acid and derivatives thereof, a skin-
drying
agent, a corticosteroid, a non-steroidal anti-inflammatory agent, and an anti-
seborrhea agent.
81.The method of claim 65, wherein the antibiotic agent is suitable for the
treatment of rosacea and the additional active agent is selected from the
group consisting of a retinoid; a keratolytic acid, an alpha-hydroxy acid, a
beta-hydroxy acid, a corticosteroid and a non-steroidal anti-inflammatory
agent.
82.The method of claim 65, wherein the antibiotic agent is suitable for the
treatment of otitis and the additional active agent is selected from the group
consisting of an antifungal agent, a topical anesthetic agent, a
corticosteroid
and a non-steroidal anti-inflammatory agent.
83.The kit of claim 1, wherein the surface-active agent comprises a
combination
of at least one non-ionic surfactant having HLB of less than 9 and at least
one
non-ionic surfactant having HLB of equal or more than 9, wherein the ratio
between the at least one non-ionic surfactant having HLB of less than 9 and
the at least one non-ionic surfactant having HLB of equal or more than 9, is
between 1:4 and 4:1.
84. The kit of claim 83, wherein the resulting HLB value of the combination of
at
least one non-ionic surfactant having HLB of less than 9 and at least one non-
92
ionic surfactant having HLB of equal or more than 9 is between about 9 and
about 14.
85. The composition of claim 34, wherein the surface-active agent consists of
one
or more non-ionic surfactants.
86. The composition of claim 34, wherein the surface-active agent comprises a
combination of at least one non-ionic surfactant having HLB of less than 9 and
at least one non-ionic surfactant having HLB of equal or more than 9, wherein
the ratio between the at least one non-ionic surfactant having HLB of less
than 9 and the at least one non-ionic surfactant having HLB of equal or more
than 9, is between 1:8 and 8:1.
87. The composition of claim 86, wherein the resulting HLB value of the
combination of at least one non-ionic surfactant having HLB of less than 9 and
at least one non-ionic surfactant having HLB of equal or more than 9 is
between about 9 and about 14.
88. The composition of claim 34, wherein the surface-active agent comprises a
combination of a non-ionic surfactant and an ionic surfactant, at a ratio of
between about 4:1 and about 1:4.
89. The method of claim 60, wherein the surface-active agent comprises a
combination of at least one non-ionic surfactant having HLB of less than 9 and
at least one non-ionic surfactant having HLB of equal or more than 9, wherein
the ratio between the at least one non-ionic surfactant having HLB of less
than 9 and the at least one non-ionic surfactant having HLB of equal or more
than 9, is between 1:8 and 8:1.
90. The method of claim 89, wherein the resulting HLB value of the combination
of at least one non-ionic surfactant having HLB of less than 9 and at least
one
non-ionic surfactant having HLB of equal or more than 9 is between about 9
and about 14.
93
91. The method of claim 60, wherein the surface-active agent comprises a
combination of a non-ionic surfactant and an ionic surfactant, at a ratio of
between about 4:1 and about 1:4.
94
