WO1998016104A1 - Antimicrobial lipids - Google Patents
Antimicrobial lipids Download PDFInfo
- Publication number
- WO1998016104A1 WO1998016104A1 PCT/US1997/018826 US9718826W WO9816104A1 WO 1998016104 A1 WO1998016104 A1 WO 1998016104A1 US 9718826 W US9718826 W US 9718826W WO 9816104 A1 WO9816104 A1 WO 9816104A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- compound
- composition
- pharmaceutically acceptable
- hydrocarbon
- fatty acid
- Prior art date
Links
- 150000002632 lipids Chemical class 0.000 title claims abstract description 39
- 230000000845 anti-microbial effect Effects 0.000 title claims description 32
- 239000000203 mixture Substances 0.000 claims abstract description 120
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 48
- 239000000194 fatty acid Substances 0.000 claims abstract description 48
- 229930195729 fatty acid Natural products 0.000 claims abstract description 48
- 150000004665 fatty acids Chemical class 0.000 claims abstract description 34
- 150000001875 compounds Chemical class 0.000 claims description 59
- 238000000034 method Methods 0.000 claims description 41
- 150000003839 salts Chemical class 0.000 claims description 34
- 150000002430 hydrocarbons Chemical class 0.000 claims description 29
- 239000004215 Carbon black (E152) Substances 0.000 claims description 28
- 239000002253 acid Substances 0.000 claims description 28
- 229930195733 hydrocarbon Natural products 0.000 claims description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 27
- -1 glyceryl fatty acid ester Chemical class 0.000 claims description 23
- 208000015181 infectious disease Diseases 0.000 claims description 22
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
- 239000004599 antimicrobial Substances 0.000 claims description 15
- 241001465754 Metazoa Species 0.000 claims description 14
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 claims description 12
- 239000002674 ointment Substances 0.000 claims description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 11
- 125000002947 alkylene group Chemical group 0.000 claims description 10
- 239000011734 sodium Substances 0.000 claims description 9
- 230000000813 microbial effect Effects 0.000 claims description 7
- 125000005233 alkylalcohol group Chemical group 0.000 claims description 6
- 239000012867 bioactive agent Substances 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 5
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 5
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 5
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 5
- 206010000496 acne Diseases 0.000 claims description 5
- 125000005210 alkyl ammonium group Chemical group 0.000 claims description 5
- 229910052788 barium Inorganic materials 0.000 claims description 5
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 claims description 5
- 239000011575 calcium Substances 0.000 claims description 5
- 229910052791 calcium Inorganic materials 0.000 claims description 5
- 229910052802 copper Inorganic materials 0.000 claims description 5
- 239000010949 copper Substances 0.000 claims description 5
- 230000002708 enhancing effect Effects 0.000 claims description 5
- 229910052709 silver Inorganic materials 0.000 claims description 5
- 239000004332 silver Substances 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- 229910052725 zinc Inorganic materials 0.000 claims description 5
- 239000011701 zinc Substances 0.000 claims description 5
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 3
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 3
- 238000004321 preservation Methods 0.000 claims description 3
- 239000002324 mouth wash Substances 0.000 claims description 2
- 229940051866 mouthwash Drugs 0.000 claims description 2
- 239000002453 shampoo Substances 0.000 claims description 2
- 229940034610 toothpaste Drugs 0.000 claims description 2
- 239000000606 toothpaste Substances 0.000 claims description 2
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 claims 1
- 229920000233 poly(alkylene oxides) Polymers 0.000 claims 1
- 244000005700 microbiome Species 0.000 abstract description 5
- 231100000331 toxic Toxicity 0.000 abstract description 2
- 230000002588 toxic effect Effects 0.000 abstract description 2
- 210000003491 skin Anatomy 0.000 description 34
- 238000006243 chemical reaction Methods 0.000 description 25
- 210000000434 stratum corneum Anatomy 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- 210000001519 tissue Anatomy 0.000 description 18
- 241000894006 Bacteria Species 0.000 description 17
- 239000002904 solvent Substances 0.000 description 16
- 239000000047 product Substances 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 239000000499 gel Substances 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
- 241000233866 Fungi Species 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 239000004698 Polyethylene Substances 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 239000003124 biologic agent Substances 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- YVSFLVNWJIEJRV-UHFFFAOYSA-N 1-undecyne Chemical compound CCCCCCCCCC#C YVSFLVNWJIEJRV-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 206010052428 Wound Diseases 0.000 description 6
- 208000027418 Wounds and injury Diseases 0.000 description 6
- 239000006071 cream Substances 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 238000013019 agitation Methods 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000003085 diluting agent Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000008273 gelatin Substances 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 235000011852 gelatine desserts Nutrition 0.000 description 5
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 5
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 5
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 5
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- NIDSRGCVYOEDFW-UHFFFAOYSA-N 1-bromo-4-chlorobutane Chemical compound ClCCCCBr NIDSRGCVYOEDFW-UHFFFAOYSA-N 0.000 description 4
- JEHXPDGOCDROSG-UHFFFAOYSA-N 1-chloropentadec-4-yne Chemical compound CCCCCCCCCCC#CCCCCl JEHXPDGOCDROSG-UHFFFAOYSA-N 0.000 description 4
- 241000222122 Candida albicans Species 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 238000007792 addition Methods 0.000 description 4
- 230000001476 alcoholic effect Effects 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 230000001332 colony forming effect Effects 0.000 description 4
- ZQPPMHVWECSIRJ-MDZDMXLPSA-N elaidic acid Chemical compound CCCCCCCC\C=C\CCCCCCCC(O)=O ZQPPMHVWECSIRJ-MDZDMXLPSA-N 0.000 description 4
- 210000002615 epidermis Anatomy 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 231100000344 non-irritating Toxicity 0.000 description 4
- SECPZKHBENQXJG-FPLPWBNLSA-N palmitoleic acid Chemical compound CCCCCC\C=C/CCCCCCCC(O)=O SECPZKHBENQXJG-FPLPWBNLSA-N 0.000 description 4
- 239000001814 pectin Substances 0.000 description 4
- 235000010987 pectin Nutrition 0.000 description 4
- 229920001277 pectin Polymers 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
- 230000032258 transport Effects 0.000 description 4
- 210000001835 viscera Anatomy 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 102000004142 Trypsin Human genes 0.000 description 3
- 108090000631 Trypsin Proteins 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 230000004888 barrier function Effects 0.000 description 3
- 238000006297 dehydration reaction Methods 0.000 description 3
- 238000004817 gas chromatography Methods 0.000 description 3
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 3
- 239000000416 hydrocolloid Substances 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000007794 irritation Effects 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- 244000045947 parasite Species 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 3
- 230000002685 pulmonary effect Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 230000036556 skin irritation Effects 0.000 description 3
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 239000012588 trypsin Substances 0.000 description 3
- WHBMMWSBFZVSSR-GSVOUGTGSA-N (R)-3-hydroxybutyric acid Chemical compound C[C@@H](O)CC(O)=O WHBMMWSBFZVSSR-GSVOUGTGSA-N 0.000 description 2
- YUBSSAFQFZDRNW-UHFFFAOYSA-N 1-chloroheptadec-6-yne Chemical compound CCCCCCCCCCC#CCCCCCCl YUBSSAFQFZDRNW-UHFFFAOYSA-N 0.000 description 2
- QSPXMKGHSLKDEO-UHFFFAOYSA-N 1-chloropentadec-5-yne Chemical compound CCCCCCCCCC#CCCCCCl QSPXMKGHSLKDEO-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 241001125671 Eretmochelys imbricata Species 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 229910018954 NaNH2 Inorganic materials 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 235000021314 Palmitic acid Nutrition 0.000 description 2
- 235000021319 Palmitoleic acid Nutrition 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 241000194024 Streptococcus salivarius Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 235000015278 beef Nutrition 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- SECPZKHBENQXJG-UHFFFAOYSA-N cis-palmitoleic acid Natural products CCCCCCC=CCCCCCCCC(O)=O SECPZKHBENQXJG-UHFFFAOYSA-N 0.000 description 2
- ILLHQJIJCRNRCJ-UHFFFAOYSA-N dec-1-yne Chemical compound CCCCCCCCC#C ILLHQJIJCRNRCJ-UHFFFAOYSA-N 0.000 description 2
- 230000007682 dermal toxicity Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- DGHQYXMNBSTPNF-UHFFFAOYSA-N methyl hexadec-6-ynoate Chemical compound CCCCCCCCCC#CCCCCC(=O)OC DGHQYXMNBSTPNF-UHFFFAOYSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 238000007747 plating Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000009993 protective function Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 210000002374 sebum Anatomy 0.000 description 2
- 231100000438 skin toxicity Toxicity 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 210000000707 wrist Anatomy 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 1
- DQHKCMPDSGCTHI-UHFFFAOYSA-N 1-bromo-1-chlorobutane Chemical compound CCCC(Cl)Br DQHKCMPDSGCTHI-UHFFFAOYSA-N 0.000 description 1
- JTYUIAOHIYZBPB-UHFFFAOYSA-N 1-bromo-6-chlorohexane Chemical compound ClCCCCCCBr JTYUIAOHIYZBPB-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- ZXSWZQSYZYMZKS-UHFFFAOYSA-N 2-methoxyethyl 4-(3-hydroxyphenyl)-7-(2-methoxyphenyl)-2-methyl-5-oxo-4,6,7,8-tetrahydro-1h-quinoline-3-carboxylate Chemical compound COCCOC(=O)C1=C(C)NC(CC(CC2=O)C=3C(=CC=CC=3)OC)=C2C1C1=CC=CC(O)=C1 ZXSWZQSYZYMZKS-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 241000167854 Bourreria succulenta Species 0.000 description 1
- 241000589513 Burkholderia cepacia Species 0.000 description 1
- 241001136175 Burkholderia pseudomallei Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- BHYOQNUELFTYRT-UHFFFAOYSA-N Cholesterol sulfate Natural products C1C=C2CC(OS(O)(=O)=O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 BHYOQNUELFTYRT-UHFFFAOYSA-N 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- 241000207199 Citrus Species 0.000 description 1
- 241000186427 Cutibacterium acnes Species 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- 241001600125 Delftia acidovorans Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 208000009366 Echinococcosis Diseases 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 206010061126 Escherichia infection Diseases 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 229920000569 Gum karaya Polymers 0.000 description 1
- 206010019375 Helicobacter infections Diseases 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010061259 Klebsiella infection Diseases 0.000 description 1
- 208000024233 Klebsiella infectious disease Diseases 0.000 description 1
- 229920000161 Locust bean gum Polymers 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- BYBLEWFAAKGYCD-UHFFFAOYSA-N Miconazole Chemical compound ClC1=CC(Cl)=CC=C1COC(C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 BYBLEWFAAKGYCD-UHFFFAOYSA-N 0.000 description 1
- 241001480037 Microsporum Species 0.000 description 1
- 241000893980 Microsporum canis Species 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 241000041995 Pelargonium ovale Species 0.000 description 1
- 240000007711 Peperomia pellucida Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 206010035502 Plasmodium ovale infection Diseases 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
- 208000032536 Pseudomonas Infections Diseases 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 241000589540 Pseudomonas fluorescens Species 0.000 description 1
- 241000589630 Pseudomonas pseudoalcaligenes Species 0.000 description 1
- 241000589614 Pseudomonas stutzeri Species 0.000 description 1
- 241000317803 Pseudoxya diminuta Species 0.000 description 1
- 241000812330 Pyrenochaeta Species 0.000 description 1
- 208000035415 Reinfection Diseases 0.000 description 1
- 241000122799 Scopulariopsis Species 0.000 description 1
- 241000825258 Scopulariopsis brevicaulis Species 0.000 description 1
- 206010061512 Serratia infection Diseases 0.000 description 1
- 241000607715 Serratia marcescens Species 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000122973 Stenotrophomonas maltophilia Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
- 240000006474 Theobroma bicolor Species 0.000 description 1
- 241000223230 Trichosporon Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 239000004164 Wax ester Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- 229940125687 antiparasitic agent Drugs 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Inorganic materials [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 1
- 238000010945 base-catalyzed hydrolysis reactiony Methods 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000007942 carboxylates Chemical group 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 229940106189 ceramide Drugs 0.000 description 1
- 150000001783 ceramides Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 235000019693 cherries Nutrition 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 150000001840 cholesterol esters Chemical class 0.000 description 1
- BHYOQNUELFTYRT-DPAQBDIFSA-N cholesterol sulfate Chemical compound C1C=C2C[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 BHYOQNUELFTYRT-DPAQBDIFSA-N 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- JEVCWSUVFOYBFI-UHFFFAOYSA-N cyanyl Chemical compound N#[C] JEVCWSUVFOYBFI-UHFFFAOYSA-N 0.000 description 1
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000000469 ethanolic extract Substances 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- 229940117927 ethylene oxide Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 150000002190 fatty acyls Chemical group 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 208000024693 gingival disease Diseases 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- OMEMMZJIJNUXIH-UHFFFAOYSA-N hexadec-6-ynoic acid Chemical compound CCCCCCCCCC#CCCCCC(O)=O OMEMMZJIJNUXIH-UHFFFAOYSA-N 0.000 description 1
- QKGYJVXSKCDGOK-UHFFFAOYSA-N hexane;propan-2-ol Chemical compound CC(C)O.CCCCCC QKGYJVXSKCDGOK-UHFFFAOYSA-N 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 235000010494 karaya gum Nutrition 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 235000010420 locust bean gum Nutrition 0.000 description 1
- 239000000711 locust bean gum Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- 229960002509 miconazole Drugs 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000002911 mydriatic effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229940087419 nonoxynol-9 Drugs 0.000 description 1
- 229920004918 nonoxynol-9 Polymers 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- TWMWUMMHJZPNEO-UHFFFAOYSA-N octadec-7-ynenitrile Chemical compound CCCCCCCCCCC#CCCCCCC#N TWMWUMMHJZPNEO-UHFFFAOYSA-N 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 229940055019 propionibacterium acne Drugs 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000012048 reactive intermediate Substances 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000003441 saturated fatty acids Nutrition 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 210000001732 sebaceous gland Anatomy 0.000 description 1
- 230000004215 skin function Effects 0.000 description 1
- 238000003307 slaughter Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 230000001150 spermicidal effect Effects 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 210000000106 sweat gland Anatomy 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- FBWNMEQMRUMQSO-UHFFFAOYSA-N tergitol NP-9 Chemical compound CCCCCCCCCC1=CC=C(OCCOCCOCCOCCOCCOCCOCCOCCOCCO)C=C1 FBWNMEQMRUMQSO-UHFFFAOYSA-N 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 239000001974 tryptic soy broth Substances 0.000 description 1
- 108010050327 trypticase-soy broth Proteins 0.000 description 1
- 230000002476 tumorcidal effect Effects 0.000 description 1
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 235000019386 wax ester Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/35—Ketones, e.g. benzophenone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/361—Carboxylic acids having more than seven carbon atoms in an unbroken chain; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/37—Esters of carboxylic acids
- A61K8/375—Esters of carboxylic acids the alcohol moiety containing more than one hydroxy group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/41—Amines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/42—Amides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
- A61K8/86—Polyethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q1/00—Make-up preparations; Body powders; Preparations for removing make-up
- A61Q1/02—Preparations containing skin colorants, e.g. pigments
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q15/00—Anti-perspirants or body deodorants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/005—Antimicrobial preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
- A61Q5/02—Preparations for cleaning the hair
Definitions
- the present invention relates to compositions of certain antimicrobial skin pids and to methods of preparing and using these pids
- the invention also relates to non irritating compositions comprising these anti microbial skin pids
- the skin functions as a barrier between the outside world and the internal organs of the body It serves the protective function of keeping harmful microbial organisms from colonizing the interior of an animal Part of this protective function can be ascribed to the hpids present in epidermis, sebaceous secretions, or otherwise present at the skin surface
- the distribution of lipid types at the skin differs markedly from the distribution found in internal organs See, Nicolaides, Science, 1 86 1 9-26 ( 1 974)
- Some of these skin-derived hpids have been reported to have pharmaceutical activity in inhibiting the growth of microbial organisms See, Kabera et al , Antimicrobial Agents and Chemotherapy, 2 23-28 ( 1 972), However, many of the fatty acids among these antimicrobial lipids are known
- Non-irritating natural lipid compositions that prevent infection or biological decay are desirable, since they are unlikely to cause adverse reactions Therefore, what is needed in the art are such compositions formulated with non irritating lipids or such compositions wherein the antimicrobial action of the lipids is accentuated so that the lipids can be present at concentrations less than the threshold concentration for irritation Summary of the Invention
- a + b equals from 11 to 14 and b is an integer from 1 to 14, wherein R 5 is (a) CH 2 NR 1 R 22 , wherein R 21 and R 22 are independently hydrogen or C1 to C6 hydrocarbon, preferably C1 to C4 hydrocarbon, (b) C(0)-R 23 , R 23 is (i) NR 2 R 25 , wherein R 24 and R 25 are independently hydrogen or C1 to C6 hydrocarbon, preferably CI to C4 hydrocarbon, (n) OR 26 , wherein R 26 is glyceryl or a glyceryl fatty acid ester, wherein said fatty acid is about C15 to about C18, or (in) a hydroxyl, or (c) CH 2 OH
- R 5 is (a) CH 2 NR 1 R 22 , wherein R 21 and R 22 are independently hydrogen or C1 to C6 hydrocarbon, preferably C1 to C4 hydrocarbon, (b) C(0)-R 23 , R 23 is (i) NR 2 R 25 , wherein
- n is an integer from 3 to 6 and R 1 , R 2 , R 3 and R 4 ⁇ re independently (a) CH 2 NR 11 R 12 , wherein R 11 and R 12 are independently hydrogen or C1 to C6 hydrocarbon, preferably C1 to C4 hydrocarbon, (b) C(0)-R 13 , wherein R 13 is (i) NR 14 R 15 , wherein R 14 and R 15 are independently hydrogen or C1 to C6 hydrocarbon, preferably C1 to C4 hydrocarbon, (n) OR 16 , wherein R 16 is glyceryl or a glyceryl fatty acid ester, wherein said fatty acid is about C15 to about C18, or (in) a hydroxyl, or (c) CH 2 OH
- the hydrocarbon moieties referred to herein are preferably alkyl
- the formulas below describing fatty acid compounds are helpful to understanding the invention H H o i i II
- fatty acids ( 1 a)-(4a) described above have antimicrobial activity, particularly against a broad spectrum of gram positive bacteria, but also against other microorganisms including a number of gram negative bacteria They further inhibit the adherence of bacteria and fungi to animal skin Additionally, they are believed to be active against pid-coated viral particles C 1 6 1 ⁇ 6 and C 1 6 1 ⁇ 9 were surprisingly found to be non irri g ating, even at concentrations as high a 1 0% w/v These results were for example obtained by contacting skin with the fatty acid in a hydroxypropyl methylcellulose gel and in the presence of alcohol as high as 75 % Surprisingly, compounds of the formulas ( 1 ) - (5) have been shown to been found to have much greater antimicrobial activity when combined with an alcohol or a polyalkylene glycol
- the invention provides an antimicrobial composition
- a + b equals from 11 to 14 and b is an integer from 1 to 14, wherein R 5 is (a) CH 2 NR 21 R 22 , wherein R 21 and R 22 are independently hydrogen or C1 to C6 hydrocarbon, (b) C(0)-R 23 ,
- R 23 is (i) NR 2 R 25 , wherein R 24 and R 25 are independently hydrogen or C1 to C6 hydrocarbon, (ii) OR 26 , wherein R 26 is glyceryl or a glyceryl fatty acid .ester, wherein said fatty acid is about C15 to about C18, or (iii) a hydroxyl, or (c) CH 2 OH, or a pharmaceutically acceptable salt thereof.
- the invention provides an antimicrobial composition
- a pharmaceutically acceptable excipient and (II) an isolated compound of formula
- R 1 and R 2 are independently (a) CH 2 NR 11 R 12 , wherein R 11 and R 12 are independently hydrogen or C1 to C6 hydrocarbon, (b) C(O)- R 13 , wherein R 13 is (i) NR 14 R 15 , wherein R 14 and R 15 are independently hydrogen or C1 to C6 hydrocarbon, (ii) OR 16 , wherein R 16 is glyceryl or a glyceryl fatty acid ester, wherein said fatty acid is about C15 to about C18, or (iii) a hydroxyl, or (c) CH 2 OH, or a pharmaceutically acceptable salt thereof.
- compositions of the first and second embodiments have a number of preferred or alternative embodiments.
- the compound is according to one of the following formulas
- n is an integer from 3 to 6 and R 3 and R 4 are independently as set forth for R 5 , or a pharmaceutically acceptable salt thereof.
- the compound is of one of the following formulas
- R 1 , R 2 and R 3 are independently (d) CH 2 NR 21 R 22 , (e) C(0)-R 13" , wherein R 13' is (i) OR 26 or (n) a hydroxyl, or (f) CH 2 OH, or a pharmaceutically acceptable salt thereof.
- the compound is an ester with a monoglyce ⁇ de having a mono- or di- unsaturated fatty acyl component.
- the compound comprises an acid whereby R 1 , R 2 or R 3 comprises COOH, or a pharmaceutically acceptable salt thereof.
- the salt comprises a sodium, ammonium, silver, copper, calcium, barium, zinc or mono-, di- , t ⁇ - or quaterniary alkylammonium salt, wherein said alkyl substituents on ammonium are independently C1 to C8.
- the alkyl substituents on ammonium are independently C1 to C4 alkyl groups
- the compositions of the invention can be formulated for a device for dwelling on the skin, such as a wound dressing, ostomy device, IV tape, or the like
- such devices comprise a hydrocolloid gel
- the compositions of the invention can be adapted for application to an epithelial surface of a mammal
- the composition can be a toothpaste, mouthwash, shampoo, hair styling composition, skin ointment, make-up composition, anti-oderant or antipersperant
- the compositions of the invention can be used to treat or prevent an infection of the gastrointestinal tract comprising administering an antimicrobially effective amount of an antimicrobial composition of the invention
- the infection to be treated or prevented can be a Helicobacter pylori infection
- the compositions of the invention can be used to treat or prevent acne by administering an antimicrobially effective amount of an antimicrobial composition of the invention
- the amount of the antimicrobial composition administered is effective
- the invention further provides a lipid-replenishing skin treatment ointment comprising (a) the antimicrobial composition of claim 1 , and (b) a plurality of lipids selected from the pids normally present on skin
- compositions of the invention can be adapted for topical or oral administration, such as a cream adapted for topical administration
- the invention provides a method of treating or preventing infection, the method comprising applying or administering to an animal a composition comprising an antimicrobially effective amount of a compound selected from the group consisting of H H
- n is an integer from 3 to 6 and R 4 is (a) CH 2 NR 31 R 32 , wherein R 31 and R 32 are independently hydrogen or C 1 to C6 hydrocarbon, (b) C(O)-R 33 , wherein R 33 is (i) NR 34 R 35 , wherein R 34 and R 35 are independently hydrogen or C 1 to C6 hydrocarbon, (n) OR 36 , wherein R 36 is glyceryl or a glyceryl fatty acid ester, wherein said fatty acid is about C 1 5 to about C 1 8, or (in) a hydroxyl, or (c) CH 2 OH, or a pharmaceutically acceptable salt of said compound
- the invention provides a method of treating or preventing infection, comprising-
- a + b equals from 1 1 to 1 4 and b is an integer from 1 to 1 4, wherein R 5 is as set forth above, or a pharmaceutically acceptable salt thereof, and
- R 1 and R 2 are independently (d) CH 2 NR 21 R 22 , (e) C(0)-R 1 3 ' , or (f) CH 2 OH, or a pharmaceutically acceptable salt thereof. All of the preferred or alternative embodiments described above for the compositions are, of course, applicable to these methods.
- the infection to be treated or prevented is caused by gram negative bacteria.
- the infection to be treated or prevented is caused by a drug-resistant microbe, such as a drug-resistant bacteria, which can be a MRSA.
- the infection to be treated or prevented is caused by a fungus.
- the treatment and prevention methods of the invention can also be used to prevent the adherence of a microbe to epithelial surfaces.
- the component is applied prior to the compound of formula ( 5) .
- the invention provides transdermal administration forms and methods .
- a transdermal administration form for a biological agent comprising : (a) a bioactive agent; and (b) a transdermal transport effective amount of a compound as follows:
- the method of transdermal administration of a biological agent comprises the steps of: (a) topically applying a biological agent to a site on an animal; and (b) applying to the site a transdermal transport effective amount of a compound as follows:
- a + b equals from 1 1 to 1 4 and b is an integer from 1 to 1 4, wherein R 5 is as set forth above, or a pharmaceutically acceptable salt thereof.
- the applying step (b) occurs prior to or concurrently with applying step (a) .
- the invention provides a preservation method and preserved materials. Accordingly, the invention provides a method of preserving a biologically degradable composition comprising contacting the composition with a preservation effective amount of a a compound as follows:
- a + b equals from 1 1 to 1 4 and b is an integer from 1 to 14, wherein R 5 is as set forth above, or a pharmaceutically acceptable salt thereof.
- the invention also provides preserved compositions comprising the product of the method.
- antimicrobial activity encompasses killing microbes, inhibiting the reproduction of microbes, and inhibiting the adherence of microbes to animal tissue.
- An antimicrobially effective amount of a compound of formulas ( 1 )-(5) is an amount effective to either (a) reduce the symptoms of a microbial disease sought to be treated, (b) induce a pharmacological change relevant to treating a microbial disease sought to be treated, (c) inhibit or prevent infection or re-infection by a microbial agent, or (d) reduce the adherence of a microbial agent to a tissue. Since the compositions of the inventions can accentuate the activity compounds of formulas
- an antimicrobially effective amount is an amount effective when delivered in the relevant composition.
- an effective amount includes an amount which, if regularly applied, prevents the occurrence of infection.
- a bioactive agent is an agent that is useful for diagnosing or imaging or that can act on a cell, organ or organism, including but not limited to drugs (pharmaceuticals) to create a change in the functioning of the cell, organ or organism.
- Such agents can include but are not limited to nucleic acids, polynucleotides, antibacterial agents, antiviral agents, antifungal agents, anti-parasitic agents, tumoricidal or anti-cancer agents, proteins, toxins, enzymes, hormones, neurotransmitters, glycoproteins, immunoglobulins, immunomodulators, dyes, radiolabels, radio-opaque compounds, fluorescent compounds, polysaccharides, cell receptor binding molecules, anti-inflammatories, anti-glaucomic agents, mydriatic compounds and local anesthetics.
- an excipient is an inert substance used as a diluent or carrier for a pharmaceutically active substance.
- an ionizable group is a moiety that is predominantly in an ionized form at physiological pH.
- an isolated compound is a compound having at least about 60% wt/wt purity.
- a microbe is a bacteria, mycoplasma, yeast or fungi, virus or parasite (such as a malaria parasite) .
- a microbe adherence inhibiting effective amount of a compound is an amount that causes a reduction in the portion of a defined inoculum of a microbe that adheres to a tissue to which the microbe normally adheres
- oral administration includes any administration into the gastrointestinal tract, including rectal administration
- a substantially purified compound shall be one that has a purity of at least about 85% wt/wt • topical administration includes administration to the tissues that form a barrier between the external environment and the internal organs of an animal, including without limitation administration to the skin, gums, buccal tissue, nasal and sinus tissue, ocular tissue, mtraurethral tissue, rectal tissue or intravaginal tissue • a transdermal transport effective amount of a compound shall be an amount of the compound that leads to an increase in the amount of a topically applied biological agent that reaches the blood stream of an animal to which the biological agent was applied.
- Figure 1 shows a schematic for a synthesis of C 1 6 1 ⁇ 6
- Figure 2 shows a timecourse for the adherence of C albicans to stratum corneum
- Figure 3 shows the adherence activity of various Candida isolates
- Figure 4 shows the adherence of C albicans to stratum corneum, stratum corneum with added skin li id, and lipid depleted stratum corneum
- Figure 5 shows the effect of adding various fractions of skin lipid to stratum corneum discs
- Figure 6 shows the effect of adding C 1 6 1 ⁇ 6 and C 1 6 1 ⁇ 9 to stratum corneum discs
- Figure 7 shows the bacteriocidal activity C 1 6 : 1 ⁇ 6 against 5. aureus.
- compositions containing a fatty acid or derivative of formulas ( 1 )-( 5) comprise a substantially purified fatty acid or derivative of formulas ( 1 )-( 5)
- the fatty acid or derivative shall comprise at least about 0 01 % wt/wt of the composition More preferably the fatty acid or derivative will comprise at least about 0 05 % of the composition, still more preferably at least about 0. 1 % .
- the composition includes a compound of formulas ( 1 )-( 5) that lacks an tonizable group in the R 1 , R 2 , R 3 , R 4 , or R 5 group, but which is convertible to an tonizable group by either a hydrolysis or oxidation reaction.
- the compound is convertible by a hydrolysis reaction
- the compound is converted to an acid, or a salt thereof More preferably, the convertible compound is an ester of an acid
- Preferred fatty acids or derivatives for use in the invention will have a primary dermal irritation index of less than about 2 PDI I grade when 0 2 mg of fatty acid or derivative is applied to a 1 0 cm 2 portion of a rabbit ear, more preferably less than about 1 PDII grade under these conditions
- a suitable non-irritating diluent for use in comparative irritation measurements comprises a gel ointment of 2.5% hydroxypropyl methylcellulose in a water/alcohol mixture comprising from 5 to 75 % of an alcohol such as ethanol or propanol.
- the gel can contain other suitable exipients or carriers.
- the compounds of formulas ( 1 ) - ( 5) will comprise between about 0 1 % and 5.0% (w/v) of the composition , more preferably between about 0 3% and 3.0% , still more preferably between about 0 4% and 1 0% .
- compositions of the invention can be administered to an animal such as a human in need of protection from microorganisms or of treatment for an infection Typical modes of administration will include topical, oral, parenteral or pulmonary (by use of an aerosol) administration
- the compositions can be administered alone, or they can be combined with a pharmaceutically-acceptable excipient according to standard pharmaceutical practice
- excipients will be selected to be appropriate to allow the formation of an aerosol
- the fatty acids and derivatives of the invention are used in the form of tablets, capsules, lozenges, chewing gum, troches, powders, syrups, elixirs, aqueous solutions and suspensions, and the like
- carriers that is used include lactose, sodium citrate and salts of phosphoric acid
- dismtegrants such as starch, and lubricating agents such as magnesium stearate and talc, are commonly used in tablets
- useful diluents are commonly used in tablets.
- Suppository forms of the fatty acids and derivatives of the invention are useful for vaginal, urethral and rectal administrations
- Such suppositories will generally be constructed of a mixture of substances that is solid at room temperature but melts at body temperature
- the substances commonly used to create such vehicles include theobroma oil, glyce ⁇ nated gelatin, hydrogenated vegetable oils, mixtures of polyethylene glycols of various molecular weighty and fatty acid esters of polyethylene glycol See, Remington's Pharmaceutical
- Analogous gels or creams can be used for vaginal, urethral and rectal administrations
- compositions of the invention are preferably administered via devices for dwelling on the skin such as wound dressings, ostomy devices, IV tapes, and the like
- the wound dressing will preferably be designed to administer to the wound or adjacent skin an antimicrobial effective amount c f a compound of formulas ( 1 ) (5)
- suitable dressings a-e found, for example, in U S Patent Nos 4,909, 243, 4, 538, 603, 5, 244,457 and 5,308,31 3
- the compositions of the invention are formulated in hydrocolloid gels Such gels typically include water soluble hydrocolloids such as pectin, gelatin, guar gum, locust bean gum, gum karaya, and mixtures thereof Pectin and gelatin are preferred
- the invention is believed to function by limiting the growth of bacteria or limiting the skin adherence of bacteria, where the bacteria is associated with the formation of acne lesions.
- the invention also provides for the treatment or prevention of gram negative infections or infections by microbes that have acquired drug resistance, such as methacillin resistant Staphy/ococc ⁇ s a ⁇ reus ("MRSA") .
- MRSA methacillin resistant Staphy/ococc ⁇ s a ⁇ reus
- Preferred gram negative targets for treatment or prevention include Pseudomonas infections, such as those caused by P. acidovorans, P. aeruginosa, P. cepacia, P. diminuta, P. fluorescens, P. maltophilia, P. pseudoalcaligenes, P. pseudomallei, P. pyocyanea and P. stutzeri, Escherichia infections such as those caused by E.
- Preferred parasite targets for treatment or prevention include Echinococcus infections.
- Preferred fungal treatment or prevention targets include for example Candida fungi such as C. Albicans, Pityrosporum fungi such as P. ovale or P. orbiculore, Trichosporon funge such as T. rubr ⁇ mi, T. tonurans or T. interigitale, Microsporum fungi such as M. canis or M. a ⁇ douinii, Aspergillus fungi, Pyrenochaeta fungi, Scopulariopsis fungi such as S. brevicaulis and Acrononium fungi. All of the above-recited fungi are classified as yeast.
- the preferred tissues for treatment with the anti-adherence compounds of the invention are skin, stomach, urinary tract, and intravagmal tissues. Skin is most preferred.
- the ointment will generally comprise no more than about 5 % (wt/wt) of a compound according to formula (5) .
- the ointment will comprise no more than about 1 % of a compound according to formula (5) , more preferably, no more than about 0.5% .
- the transdermal administration form of the invention can be used to administer biological agents across any of the several barrier tissues separating the outside environment from the internal organs, including without limitation the skin, gums, buccal tissue, rectal tissue, nasal tissue and sinus membranes
- the compounds of formulas ( 1 )-(5) can be applied to the subject before, concurrently with, or after the application of the biological agent that is to be transdermally administered
- the animals to be treated with the various compositions of the invention are preferably mammals, particularly humans.
- the invention encompasses using a cream or ointment according to the invention in conjunction with ostomy products
- a cream of the invention can be used to coat the face plates or seals on ostomy products See, for example, U.S. Patent Nos. 4,465,486, 4,490, 1 45, 4,460,363 and 4,826,493.
- the invention further encompasses using the fatty acids or derivatives as additives to antimicrobial compositions that further include other active agents such as antimicrobials (such as antibiotics, including bacitracm) , antifungal agents (such as miconazole and t ⁇ conazole) , spermicidals (such as nonoxynol-9), and the like.
- antimicrobials such as antibiotics, including bacitracm
- antifungal agents such as miconazole and t ⁇ conazole
- spermicidals such as nonoxynol-9
- compositions of the invention are preferably formulated to have pH less than about 7, to minimize irritation to the treatment subject
- the component of the invention is preferably a (C2-C7) alkyl alcohol or a polyf alkylene oxide) wherein the alkylene moieties are C2 to C4, or mixtures of alcohol and polyfalkylene oxide)
- the alcohol is C2-C4, more preferably C3, still more preferably isopropanol
- the alkylene of the polyfalkylene oxide) is preferably C2 C3
- the polyfalkylene oxide) can be a copolymer of differing alkylene subunits Isopropyl alcohol is a preferred alcoholic component used with the invention.
- Preferred alkyleneoxide polymers include those with ethyleneoxide or propyleneoxide polymer building blocks such as polyethylene glycol and polypropylene glycol.
- the average molecular weight of the polymer is preferably between about 400 and about 1 ,000, more preferably between about 400 and about 800.
- Various weight-range polymer compositions can be mixed to obtain the consistency desired for a particular composition.
- Compositions of fatty acid-related compounds according to formulas ( 1 )-(5) and an alcoholic component have the following preferred compositions:
- compositions of fatty acid-related compounds according to formulas ( 1 )- (5) and a polymeric component have the following preferred compositions:
- compositions of fatty acid-related compounds according to formulas ( 1 )- (5), an alcoholic component and a polymeric component have the following preferred compositions:
- the solvent conditions must be sufficiently basic to favor proton abstraction from decyne.
- a mixture of ammonia and NaNH 2 in tetrahydrofuran is a preferred reaction medium Temperatures that are low enough to maintain the ammonia in liquid form are preferred.
- the undecyne (for example, from Lancaster Co. , Windham, NH) is added to the basic solvent incrementally.
- the solvent is preferably anhydrous and aprotic
- the solvent is also polar Dimethylsulfoxide (“DMSO”) is a preferred solvent
- DMSO Dimethylsulfoxide
- Potassium cyanide is the preferred source of cyanide anion
- the nit ⁇ le functionality is converted to a carboxylate functionality
- a hydrolytic reaction such as using acidic or basic hydrolytic conditions, as will be recognized by those of ordinary skill
- the hydrolysis is accomplished in an acidic, alcoholic solvent
- Particularly preferred is a mixture of methanolic HCI and concentrated H 2 S0 4 These preferred conditions will generate the alcohol ester derivative of the nit ⁇ le
- the fourth reaction comprises a hydrolysis reaction
- Conditions effective to hydrolyze an ester are well known to those of ordinary skill
- One such method is base-catalyzed hydrolysis, for instance using 0 5% wt/v NaOH in a mixture of 1 00 ml H 2 0 and 300 ml methanol (which is added to increase the solubility of the ester)
- ester hydrolyses proceed at a modest temperature, such as room temperature
- the catalyst is preferably palladium on barium sulfate (for example, 5% palladium on sulfate from Ald ⁇ ch Chemical Co , Milwaukee, WI)
- the solvent is selected to "poison" the catalyst to adjust its reactivity
- Pyridine and quinoline are appropriate solvent components for so adjusting catalyst reactivity
- Anhydous pyridine is the preferred solvent
- the amine compounds of formulas ( 1 ) - (5) can be synthesized, for example by reducing the corresponding amides with a hydride as described, for example, in Section 4 1 of Carey and Sundberg, Advanced Organic Chemistry, Part B, Plenum Press, New York, 1 977 or by Hoffmann rearrangement to remove the carbonyl moiety, as described in Wallis and Lane, Org. React. 3: 267, 1 946.
- the amide compounds of formulas ( 1 ) - (5) can be synthesized, for instance, by conducting a dehydration reaction between the corresponding fatty acid and NHR 1 R 15 .
- Such a reaction can be conducted by first forming an activated derivative of the acid such as an anhydride or an N-hydroxysuccinimide ester.
- the dehydration reaction can be conducted using a carbodiimide compound to form a reactive intermediate with the acid moiety.
- the acid synthesized as described above can be converted to the acid halide, for instance by reaction with a halogen gas in the presence of phosphorus or with a halogen-substituted phosphorus compound such as phosphorus trichloride, and subsequently reacted with the amine moiety.
- care should be taken to limit ⁇ -halogenation.
- the alcohol compounds of formulas ( 1 ) - (5) wherein R 1 , R 1 , R 1 , R 3 , R 4 , or R 5 is an ester with glycerol or monoglyceride or can be formed using the same dehydration reactions described above.
- the alcohol compounds of formulas ( 1 ) - (5) wherein R 1 , R 1 , R 1 , R 1 , R 3 , R 4 , or R 5 is an ester with glycerol or monoglyceride or can be formed using the same dehydration reactions described above.
- R 3 , R 4 , or R 5 is CH 2 OH
- R 3 , R 4 , or R 5 is CH 2 OH
- R 3 , R 4 , or R 5 is CH 2 OH
- the flask was cooled to -78 ° C in a solid carbon dioxide (dry ice)-acetone bath .
- a mixture of dry ice and acetone was also used to cool the cold trap.
- Ammonia 1 00 ml was condensed in the cold trap.
- the ammonia was then condensed into the flask and 1 2 g (0.3 mol) of NaNH 2 was added under N 2 , creating a milky white mixture.
- 38 ml (30 g, 0.2 mol) undecyne was added dropwise over a 1 0 minute period .
- the mixture then became thick and viscous .
- Additional THF was added (70 ml) to reduce the viscosity and allow continued stirring .
- the reaction mixture was then allowed to gradually warm to 25 ° C and stirred under positive nitrogen pressure for 1 5 hours . After this, the reaction was quenched by the addition of 20 g NH 4 CI .
- the reaction mixture was then poured into 200 ml cold deionized (" Dl " ) water and 200 ml hexane was added to the resulting mixture .
- the organic layer was separated , and the aqueous layer was extracted twice more with 1 00 ml hexane.
- the combined organic layers were washed ( 1 ) with 200 ml Dl water and ( 2) with 200 ml brine (i .e. , an aqueous solution saturated with sodium chloride at 25 ° C) .
- the methyl ester product was converted to the corresponding acid by refluxing it in a solution of 20 g NaOH dissolved in 300 ml methanol and 1 00 ml Dl water for 3 hours or until completion as measured by silica gel TLC (RF for free acid is 0.35 in 70: 30: 2 PE: EE :acet ⁇ c acid) .
- RF for free acid is 0.35 in 70: 30: 2 PE: EE :acet ⁇ c acid
- the solvent was removed in vacuo to give a quantitative yield of 6-hexadecynoic acid as an oil (Optionally, the product can be recrystallized at 20 ° C from hexane to yield white crystals (M . P. 37 ° C) . However, the recrystal zation results in only 70% recovery and may be omitted) .
- the 6-hexadecyno ⁇ c acid was added to a 1 L flask with 300 ml anhydrous pyridine (Aldrich) along with 1 .0 g of 5 % Pd on BaS0 4 catalyst (oxidized from) and sealed with a rubber septum.
- the catalyst is available from Aldrich Chemical Co. , Milwaukee, WI .
- the flask (which was vented with a needle vent) was first purged with nitrogen then hydrogen through a needle cannula .
- the flask was kept under 2 lbs. positive H 2 pressure, and the reaction monitored by the uptake of hydrogen .
- HPI 1 human pathogenic Candida fungi
- HPI 2 Three strains of human pathogenic Candida fungi (HPI 1 , HPI 2 and HPI 3) (isolated from symptomatic patients)
- one candidal strain of human commensurate i e , symbiotic, non pathogenic) fungi (HCI 1 ) (isolated from asymptomatic individual)
- HCI 1 symbiotic, non pathogenic fungi
- Candida parasitosis were tested for their ability to adhere to stratum corneum using the method outlined in Example 3
- a ethanol extract of surface skin lipid was prepared as described in Wertz et al , J Invest Dermatol 84 410-41 2, 1 985 Briefly, human volunteers positioned the wrist portions of their arms over a stainless steel basin, with the hand and the rest of the arm angled up and away from the basin A 250 ml portion of 95% ethanol was slowly poured over each wrist and the lipids that extracted into the ethanol were recovered by evaporating the solvent
- a part of the skin lipid extract described in Example 5 was fractionated on a preparative (0 25 mm thick) silica gel plate (Adsorbosil plus one ® , Alltech Associates, Deerfield, IL) developed with hexane ethyl ether acetic acid, 70.30 1 (v.v) Lipid fractions were located using a scanning photodensitometer set at 21 0 nm The lipid-containing regions of the plate were scrapped and the lipids eluted using chloroform:methanol water, 50: 50 1 . By this method, fractions containing ( 1 ) squalene ("SQ”), (2) wax esters and cholesterol esters
- Example 7 Inhibition of C. albicans adherence by C 1 6 : 1 ⁇ 6 and C 1 6 : 1 ⁇ 9 Using the methodology of Example 5, 0 1 , 1 0 and 1 0 0 mg of C 1 6. 1 ⁇ 6 or C 1 6 1 ⁇ 9 was applied to 1 cm stratum corneum discs and the effect of adherence by C albicans was measured The results are shown in Figure 6
- Example 8 Effect of Lipid on Bacteria A preparation of skin surface lipid prepared by extracting human hair clippings with chloroform methanol, 2 1 , for 2 hours at room temperature Following the extraction, the lipids were recovered by evaporating the extraction solvent The lipids of hair clippings are believed to reflect the composition of sebum free of lipid derived from sweat gland secretions The skin pids or other lipid preparations were suspended or dissolved in beef heart infusion broth (BHIB, Difco, Livonia, Ml) by so ⁇ ication (taking care not to overheat the broth)
- the lipid extracted from skin has been shown to be bacteriocidal towards S. aureus, Streptococcus salivarius, Eichinella corodens and F ⁇ sobacteri ⁇ m nucleatum (a gram negative anaerobic bacteria involved in gum disease), and to be bacteriostatic (i.e. , to prevent growth) against E. fascalis. Activity was not detected against P. aeruginosa.
- Example 9 Inhibitory Activity of Specific Lipids
- Example 8 The procedures of Example 8 were repeated using specific fatty acids and testing against both 5. aureus and S. salivarius. In this experiment, the optical density of the cultures was used to indicate the relative numbers of bacteria present, rather than measuring CFU values. The results, in terms of minimum inhibitory concentrations ( " MICs") were as follows:
- MRSA methicillin-resistant S. Aureus
- Example 1 1 - The Primary Dermal Irritation Index for Specific Compositions
- the primary dermal irritation index (“PDII”) of various compositions was measured using an albino rabbit, single insult patch test. Two test areas per rabbit were prepared by shaving both areas, and abrading one of the areas. Similarly, two matching control areas were prepared on each animal.
- the test material 0.5 ml each application, was applied to 2.5 x 2.5 cm gauze patches, and held against the test area with an impervious Vetrap brand bandage (3M, St. Paul, MN) . The patches were held in place for 24 h, at which time the treatment sites were wiped clean. The evaluations were based on observations at this 24 h timepoint and on observations at the 72 h timepoint.
- a gel composition containing a prospective antimicrobial agent was layered over the filter paper, with care taken to avoid air pockets formed between the gel and the filter. This amount of bacteria is in excess of the amount ( 1 x 1 0 5 ) considered to constitute an infection when present in one gram of tissue.
- the filters with bacteria and gel compositions were maintained at room temperature for 20 minutes.
- the filters were then placed in 25 ml of Trypticase Soy Broth Z-49 medium (available from GIBCO (Grand Island, NY) and incubated in a shaker incubator for 24 hours at 38 6 ° C at 1 32 rpm. Positive results were scored when bacteria could not be observed microscopically in the culture medium
- the polyethylene glycol was PEG-400, available from
- the gelatin was obtained from Hormel, Davenport, IA
- the pectin was obtained from Citrus Colloids, Hereford,
- compositions 1 , 3 and 4 were transparent liquids
- Composition 2 was a liquid when freshly prepared, but subsequently separated into two phases
- Compositions 5 and 6 were gels
- NaCMC sodium carboxymethylcellulose
- composition 1 0 and a corresponding composition 1 0-CMP, which lacked the fatty acid component, were tested for antimicrobial activity against E. co// using the method of Example 1 2.
- the following average optical densities were obtained for cultures grown from filters treated as indicated :
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Birds (AREA)
- Emergency Medicine (AREA)
- Dermatology (AREA)
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP97911011A EP0930821A1 (en) | 1996-10-17 | 1997-10-17 | Antimicrobial lipids |
CA002268875A CA2268875A1 (en) | 1996-10-17 | 1997-10-17 | Antimicrobial lipids |
JP10518625A JP2001502337A (en) | 1996-10-17 | 1997-10-17 | Antibacterial lipid |
AU48249/97A AU4824997A (en) | 1996-10-17 | 1997-10-17 | Antimicrobial lipids |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US73315596A | 1996-10-17 | 1996-10-17 | |
US08/733,155 | 1996-10-17 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1998016104A1 true WO1998016104A1 (en) | 1998-04-23 |
Family
ID=24946454
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1997/018826 WO1998016104A1 (en) | 1996-10-17 | 1997-10-17 | Antimicrobial lipids |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP0930821A1 (en) |
JP (1) | JP2001502337A (en) |
AU (1) | AU4824997A (en) |
CA (1) | CA2268875A1 (en) |
WO (1) | WO1998016104A1 (en) |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998058627A1 (en) * | 1997-06-20 | 1998-12-30 | Sabine Ebeling | A skin-protective composition |
EP0934742A2 (en) * | 1997-12-30 | 1999-08-11 | Ethicon, Inc. | High glycerin containing anti-microbial cleansers |
US6022896A (en) * | 1998-09-10 | 2000-02-08 | Chesebrough-Pond's Usa Co. | Petroselinic acid as an anti-irritant in compositions containing alpha-hydroxy acids |
US6042841A (en) * | 1998-03-16 | 2000-03-28 | Unilever Home & Personal Care Usa Division Of Conopco, Inc. | Cosmetic method of treating skin |
WO2002007531A1 (en) * | 2000-07-14 | 2002-01-31 | Societe Des Produits Nestle S.A. | Dietary lipids for improving skin and coat of pets |
WO2002011693A1 (en) * | 2000-08-03 | 2002-02-14 | Provincia Italiana Della Congregazione Dei Figli Dell'immacolata Concezione - Istituto Dermopatico Dell'immacolata | Sebum-like preparation to be used as lipidic component in cosmetics |
EP1231200A1 (en) * | 2001-02-07 | 2002-08-14 | Basf Aktiengesellschaft | Process for the production of cis-hexadec-6-enoic acid |
KR100607118B1 (en) * | 2000-02-15 | 2006-08-01 | 로레알 | Use of compounds which make it possible to modify the physicochemical properties of the skin and/or the mucous membranes as agents preventing or reducing the adhesion of microorganisms to the latter |
KR100607117B1 (en) * | 2000-02-15 | 2006-08-01 | 로레알 | Use of particular fatty substances which make it possible to modify the physicochemical properties of the skin and/or the mucous membranes as agents preventing or reducing the adhesion of microorganisms to the latter |
US7332179B2 (en) | 2003-12-12 | 2008-02-19 | Kimberly-Clark Worldwide, Inc. | Tissue products comprising a cleansing composition |
US7642395B2 (en) | 2004-12-28 | 2010-01-05 | Kimberly-Clark Worldwide, Inc. | Composition and wipe for reducing viscosity of viscoelastic bodily fluids |
CN104703576A (en) * | 2012-10-15 | 2015-06-10 | 莱雅公司 | Cosmetic use of a monounsaturated fatty acid or one of its salts and/or of its esters as deodorant active agent |
CN111925285A (en) * | 2019-05-13 | 2020-11-13 | 上海北卡医药技术有限公司 | Preparation method of 7-phenyl-6-heptynoic acid |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US545505A (en) * | 1895-09-03 | Composition for dressing leather | ||
US875380A (en) * | 1907-12-31 | Ludwig H Reuter | Composition for disinfecting, antiseptic, and other purposes. | |
US971681A (en) * | 1907-02-06 | 1910-10-04 | Samuel Knopf | Process of making artificial ointment-bases. |
US2372807A (en) * | 1941-07-05 | 1945-04-03 | Atlas Powder Co | Absorption bases |
US2804424A (en) * | 1951-04-24 | 1957-08-27 | American Cyanamid Co | Method of preparing a tetracycline type antibiotic-containing wound dressing |
US3883661A (en) * | 1971-11-09 | 1975-05-13 | Syntex Inc | Acne treatment |
-
1997
- 1997-10-17 WO PCT/US1997/018826 patent/WO1998016104A1/en not_active Application Discontinuation
- 1997-10-17 JP JP10518625A patent/JP2001502337A/en active Pending
- 1997-10-17 EP EP97911011A patent/EP0930821A1/en not_active Withdrawn
- 1997-10-17 CA CA002268875A patent/CA2268875A1/en not_active Abandoned
- 1997-10-17 AU AU48249/97A patent/AU4824997A/en not_active Abandoned
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US545505A (en) * | 1895-09-03 | Composition for dressing leather | ||
US875380A (en) * | 1907-12-31 | Ludwig H Reuter | Composition for disinfecting, antiseptic, and other purposes. | |
US971681A (en) * | 1907-02-06 | 1910-10-04 | Samuel Knopf | Process of making artificial ointment-bases. |
US2372807A (en) * | 1941-07-05 | 1945-04-03 | Atlas Powder Co | Absorption bases |
US2804424A (en) * | 1951-04-24 | 1957-08-27 | American Cyanamid Co | Method of preparing a tetracycline type antibiotic-containing wound dressing |
US3883661A (en) * | 1971-11-09 | 1975-05-13 | Syntex Inc | Acne treatment |
Cited By (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6461624B2 (en) | 1997-06-20 | 2002-10-08 | Sabine Eggers | Skin-protective composition |
WO1998058627A1 (en) * | 1997-06-20 | 1998-12-30 | Sabine Ebeling | A skin-protective composition |
EP0934742A2 (en) * | 1997-12-30 | 1999-08-11 | Ethicon, Inc. | High glycerin containing anti-microbial cleansers |
EP0934742A3 (en) * | 1997-12-30 | 2002-01-02 | Ethicon, Inc. | High glycerin containing anti-microbial cleansers |
US6042841A (en) * | 1998-03-16 | 2000-03-28 | Unilever Home & Personal Care Usa Division Of Conopco, Inc. | Cosmetic method of treating skin |
US6022896A (en) * | 1998-09-10 | 2000-02-08 | Chesebrough-Pond's Usa Co. | Petroselinic acid as an anti-irritant in compositions containing alpha-hydroxy acids |
KR100607117B1 (en) * | 2000-02-15 | 2006-08-01 | 로레알 | Use of particular fatty substances which make it possible to modify the physicochemical properties of the skin and/or the mucous membranes as agents preventing or reducing the adhesion of microorganisms to the latter |
KR100607118B1 (en) * | 2000-02-15 | 2006-08-01 | 로레알 | Use of compounds which make it possible to modify the physicochemical properties of the skin and/or the mucous membranes as agents preventing or reducing the adhesion of microorganisms to the latter |
AU2001266082B2 (en) * | 2000-07-14 | 2006-03-16 | Societe Des Produits Nestle S.A. | Dietary lipids for improving skin and coat of pets |
WO2002007531A1 (en) * | 2000-07-14 | 2002-01-31 | Societe Des Produits Nestle S.A. | Dietary lipids for improving skin and coat of pets |
US7479286B2 (en) | 2000-07-14 | 2009-01-20 | Nestec S.A. | Dietary lipids for improving skin and coat of pets |
US7625583B2 (en) | 2000-07-14 | 2009-12-01 | Nestec S.A. | Dietary lipids for improving skin and coat of pets |
WO2002011693A1 (en) * | 2000-08-03 | 2002-02-14 | Provincia Italiana Della Congregazione Dei Figli Dell'immacolata Concezione - Istituto Dermopatico Dell'immacolata | Sebum-like preparation to be used as lipidic component in cosmetics |
US6781004B2 (en) | 2001-02-07 | 2004-08-24 | Basf Aktiengesellschaft | Process for the preparation of cis-6-hexadecenoic acid |
EP1231200A1 (en) * | 2001-02-07 | 2002-08-14 | Basf Aktiengesellschaft | Process for the production of cis-hexadec-6-enoic acid |
US7332179B2 (en) | 2003-12-12 | 2008-02-19 | Kimberly-Clark Worldwide, Inc. | Tissue products comprising a cleansing composition |
US7642395B2 (en) | 2004-12-28 | 2010-01-05 | Kimberly-Clark Worldwide, Inc. | Composition and wipe for reducing viscosity of viscoelastic bodily fluids |
CN104703576A (en) * | 2012-10-15 | 2015-06-10 | 莱雅公司 | Cosmetic use of a monounsaturated fatty acid or one of its salts and/or of its esters as deodorant active agent |
CN108969406A (en) * | 2012-10-15 | 2018-12-11 | 莱雅公司 | The cosmetic use of monounsaturated fatty acids or its salt and/or one of its ester or amide as deodorant active agent |
CN104703576B (en) * | 2012-10-15 | 2018-12-18 | 莱雅公司 | The cosmetic use of monounsaturated fatty acids or its salt and/or one of its ester or amide as deodorant active agent |
CN111925285A (en) * | 2019-05-13 | 2020-11-13 | 上海北卡医药技术有限公司 | Preparation method of 7-phenyl-6-heptynoic acid |
Also Published As
Publication number | Publication date |
---|---|
EP0930821A1 (en) | 1999-07-28 |
AU4824997A (en) | 1998-05-11 |
CA2268875A1 (en) | 1998-04-23 |
JP2001502337A (en) | 2001-02-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US4411893A (en) | Topical medicament preparations | |
DE69332220T2 (en) | PROBUCOL'S SOLUBLE ANALOG | |
US11691937B2 (en) | Use of vanillin derivatives as preserving agents, preserving process, compounds and composition | |
JP3941122B2 (en) | Fast-acting and long-lasting topical disinfectant | |
US5008294A (en) | Methods of treating tumors with compositions of catecholic butanes | |
US6040347A (en) | Treatment of seborrhoea/cutaneous disorders with octoxyglycerol | |
EP0930821A1 (en) | Antimicrobial lipids | |
KR100541271B1 (en) | Antimicrobial compositions for topical use | |
AU8172487A (en) | Compositions of catecholic butanes with zinc | |
EP0109993B1 (en) | Method for extracting propolis and water soluble dry propolis powder obtained thereby and cosmetic and pharmaceutical preparations containing same | |
CA2281430A1 (en) | Skin care compositions and their use in healing injured skin | |
KR101155884B1 (en) | Chemically modified polyaminosaccharide by a hydrocarbyl sultone compound | |
EP2734195A1 (en) | Compositions for treatment of skin disorders | |
NL8601206A (en) | TRI-TRIODIC ACID ESTERS OF ERYTHROMYCIN A, PROCESS FOR THE PREPARATION THEREOF, AND PHARMACEUTICAL AND COSMETIC PREPARATIONS CONTAINING SUCH ESTERS. | |
KR102525516B1 (en) | Bakuchiol compositions for treatment of post inflammatory hyperpigmentation | |
US5064815A (en) | Primycin-containing colloidal basic gel | |
KR100539965B1 (en) | Cosmetic composition for the prevention and alleviation of atopic dermatitis comprising a novel pseudo ceramide | |
MX2011006659A (en) | Polyunsaturated fatty acid and diol ester as an anti-acne agent. | |
EP1123692A2 (en) | Use of polyaminoacid derivatives for the treatment of Seborrhea and related cutaneous disorders | |
JP3385293B2 (en) | Altocarpine-containing antibacterial and preservatives and cosmetics | |
KR100536550B1 (en) | Composition containing moutan root bark extract as active ingredient | |
CA2538429A1 (en) | Antibacterial drug for propionibacterium acnes | |
JP4220769B2 (en) | Anti-acne bacteria composition | |
JP3154712B2 (en) | Complex of neolignan derivative and phospholipid, use thereof, and pharmaceutical and cosmetic preparation containing the complex | |
EP3658160A1 (en) | Use of rhamnose and derivatives thereof as antifungal agents |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AL AM AT AU AZ BB BG BR BY CA CH CN CZ DE DK EE ES FI GB GE HU IL IS JP KE KG KP KR KZ LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK TJ TM TR TT UA UG UZ VN AM AZ BY KG KZ MD RU TJ TM |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH KE LS MW SD SZ UG ZW AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
CFP | Corrected version of a pamphlet front page |
Free format text: REVISED ABSTRACT RECEIVED BY THE INTERNATIONAL BUREAU AFTER COMPLETION OF THE TECHNICAL PREPARATIONFOR INTERNATIONAL PUBLICATION |
|
ENP | Entry into the national phase |
Ref document number: 2268875 Country of ref document: CA Ref country code: CA Ref document number: 2268875 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1997911011 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref country code: JP Ref document number: 1998 518625 Kind code of ref document: A Format of ref document f/p: F |
|
WWP | Wipo information: published in national office |
Ref document number: 1997911011 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1997911011 Country of ref document: EP |