JP2014533271A - 7−(1h−イミダゾール−4−イルメチル)−5,6,7,8−テトラヒドロキノリンを含む肌の疾患および状態を治療するための医薬組成物 - Google Patents
7−(1h−イミダゾール−4−イルメチル)−5,6,7,8−テトラヒドロキノリンを含む肌の疾患および状態を治療するための医薬組成物 Download PDFInfo
- Publication number
- JP2014533271A JP2014533271A JP2014541225A JP2014541225A JP2014533271A JP 2014533271 A JP2014533271 A JP 2014533271A JP 2014541225 A JP2014541225 A JP 2014541225A JP 2014541225 A JP2014541225 A JP 2014541225A JP 2014533271 A JP2014533271 A JP 2014533271A
- Authority
- JP
- Japan
- Prior art keywords
- skin
- ylmethyl
- imidazol
- tetrahydroquinoline
- pharmaceutical composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 35
- SIDBSMXMBWXFQV-UHFFFAOYSA-N 7-(1h-imidazol-5-ylmethyl)-5,6,7,8-tetrahydroquinoline Chemical compound C1CC2=CC=CN=C2CC1CC1=CNC=N1 SIDBSMXMBWXFQV-UHFFFAOYSA-N 0.000 title claims abstract description 19
- 208000017520 skin disease Diseases 0.000 title abstract description 43
- 238000000034 method Methods 0.000 claims abstract description 56
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 239000003814 drug Substances 0.000 claims abstract description 20
- 230000003287 optical effect Effects 0.000 claims abstract description 13
- 206010015150 Erythema Diseases 0.000 claims description 48
- 201000004700 rosacea Diseases 0.000 claims description 37
- 241001303601 Rosacea Species 0.000 claims description 31
- 238000011282 treatment Methods 0.000 claims description 31
- SIDBSMXMBWXFQV-SNVBAGLBSA-N (7r)-7-(1h-imidazol-5-ylmethyl)-5,6,7,8-tetrahydroquinoline Chemical compound C([C@@H]1CC2=NC=CC=C2CC1)C1=CNC=N1 SIDBSMXMBWXFQV-SNVBAGLBSA-N 0.000 claims description 29
- 231100000321 erythema Toxicity 0.000 claims description 28
- 201000004624 Dermatitis Diseases 0.000 claims description 22
- 206010016825 Flushing Diseases 0.000 claims description 18
- 208000003251 Pruritus Diseases 0.000 claims description 16
- 201000008937 atopic dermatitis Diseases 0.000 claims description 15
- 239000000839 emulsion Substances 0.000 claims description 15
- 230000000699 topical effect Effects 0.000 claims description 15
- 230000010339 dilation Effects 0.000 claims description 13
- 230000001815 facial effect Effects 0.000 claims description 12
- 239000000499 gel Substances 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 12
- 239000005022 packaging material Substances 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 12
- 230000024883 vasodilation Effects 0.000 claims description 12
- 230000008961 swelling Effects 0.000 claims description 11
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 10
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 10
- 206010000496 acne Diseases 0.000 claims description 10
- 208000010668 atopic eczema Diseases 0.000 claims description 10
- 239000006185 dispersion Substances 0.000 claims description 10
- SIDBSMXMBWXFQV-JTQLQIEISA-N (7s)-7-(1h-imidazol-5-ylmethyl)-5,6,7,8-tetrahydroquinoline Chemical compound C([C@H]1CC2=NC=CC=C2CC1)C1=CNC=N1 SIDBSMXMBWXFQV-JTQLQIEISA-N 0.000 claims description 9
- 239000006071 cream Substances 0.000 claims description 8
- 239000004744 fabric Substances 0.000 claims description 8
- 238000002347 injection Methods 0.000 claims description 8
- 239000007924 injection Substances 0.000 claims description 8
- 201000004681 Psoriasis Diseases 0.000 claims description 7
- 206010042496 Sunburn Diseases 0.000 claims description 7
- 239000000443 aerosol Substances 0.000 claims description 7
- 239000006260 foam Substances 0.000 claims description 7
- 238000009472 formulation Methods 0.000 claims description 7
- 239000004530 micro-emulsion Substances 0.000 claims description 7
- 239000003094 microcapsule Substances 0.000 claims description 7
- 239000002674 ointment Substances 0.000 claims description 7
- 239000007921 spray Substances 0.000 claims description 7
- 239000000725 suspension Substances 0.000 claims description 7
- 206010043189 Telangiectasia Diseases 0.000 claims description 6
- 208000016807 X-linked intellectual disability-macrocephaly-macroorchidism syndrome Diseases 0.000 claims description 6
- 239000002537 cosmetic Substances 0.000 claims description 6
- 238000011010 flushing procedure Methods 0.000 claims description 6
- 230000007803 itching Effects 0.000 claims description 6
- 239000006210 lotion Substances 0.000 claims description 6
- 239000011859 microparticle Substances 0.000 claims description 6
- 208000009056 telangiectasis Diseases 0.000 claims description 6
- 206010004146 Basal cell carcinoma Diseases 0.000 claims description 5
- 206010051625 Conjunctival hyperaemia Diseases 0.000 claims description 5
- 206010012434 Dermatitis allergic Diseases 0.000 claims description 5
- 206010012442 Dermatitis contact Diseases 0.000 claims description 5
- 208000010201 Exanthema Diseases 0.000 claims description 5
- 206010018691 Granuloma Diseases 0.000 claims description 5
- 208000006877 Insect Bites and Stings Diseases 0.000 claims description 5
- 206010051246 Photodermatosis Diseases 0.000 claims description 5
- 206010037549 Purpura Diseases 0.000 claims description 5
- 241001672981 Purpura Species 0.000 claims description 5
- 206010039793 Seborrhoeic dermatitis Diseases 0.000 claims description 5
- 208000024780 Urticaria Diseases 0.000 claims description 5
- 206010046996 Varicose vein Diseases 0.000 claims description 5
- 208000009621 actinic keratosis Diseases 0.000 claims description 5
- 230000001684 chronic effect Effects 0.000 claims description 5
- 208000010247 contact dermatitis Diseases 0.000 claims description 5
- 201000005884 exanthem Diseases 0.000 claims description 5
- 230000007794 irritation Effects 0.000 claims description 5
- 230000009245 menopause Effects 0.000 claims description 5
- 230000008845 photoaging Effects 0.000 claims description 5
- 230000001107 psychogenic effect Effects 0.000 claims description 5
- 206010037844 rash Diseases 0.000 claims description 5
- 238000002271 resection Methods 0.000 claims description 5
- 208000008742 seborrheic dermatitis Diseases 0.000 claims description 5
- 208000011580 syndromic disease Diseases 0.000 claims description 5
- 208000027185 varicose disease Diseases 0.000 claims description 5
- 206010012456 Dermatitis exfoliative generalised Diseases 0.000 claims description 4
- 208000009675 Perioral Dermatitis Diseases 0.000 claims description 4
- 206010041955 Stasis dermatitis Diseases 0.000 claims description 4
- 206010015037 epilepsy Diseases 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 238000007920 subcutaneous administration Methods 0.000 claims description 4
- 230000002381 testicular Effects 0.000 claims description 4
- 206010016936 Folliculitis Diseases 0.000 claims description 3
- 201000002154 Pterygium Diseases 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 208000024891 symptom Diseases 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 3
- 229940127557 pharmaceutical product Drugs 0.000 claims 3
- 206010015226 Erythema nodosum Diseases 0.000 claims 1
- 206010016717 Fistula Diseases 0.000 claims 1
- 206010072139 Ocular rosacea Diseases 0.000 claims 1
- 206010042674 Swelling Diseases 0.000 claims 1
- 208000003373 basosquamous carcinoma Diseases 0.000 claims 1
- 230000003890 fistula Effects 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- 210000003491 skin Anatomy 0.000 description 65
- 125000003287 1H-imidazol-4-ylmethyl group Chemical group [H]N1C([H])=NC(C([H])([H])[*])=C1[H] 0.000 description 14
- -1 vesicles Substances 0.000 description 12
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 10
- 241000699670 Mus sp. Species 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 9
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 8
- 210000001331 nose Anatomy 0.000 description 8
- 206010020751 Hypersensitivity Diseases 0.000 description 7
- 208000026935 allergic disease Diseases 0.000 description 7
- POIUWJQBRNEFGX-XAMSXPGMSA-N cathelicidin Chemical compound C([C@@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(C)C)C1=CC=CC=C1 POIUWJQBRNEFGX-XAMSXPGMSA-N 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 230000009610 hypersensitivity Effects 0.000 description 7
- 241000700159 Rattus Species 0.000 description 6
- 206010047141 Vasodilatation Diseases 0.000 description 6
- 208000014617 hemorrhoid Diseases 0.000 description 6
- WYWIFABBXFUGLM-UHFFFAOYSA-N oxymetazoline Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C)=C1CC1=NCCN1 WYWIFABBXFUGLM-UHFFFAOYSA-N 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 239000008188 pellet Substances 0.000 description 5
- 238000013268 sustained release Methods 0.000 description 5
- 239000012730 sustained-release form Substances 0.000 description 5
- 238000011200 topical administration Methods 0.000 description 5
- 230000002792 vascular Effects 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 206010020880 Hypertrophy Diseases 0.000 description 4
- 206010036790 Productive cough Diseases 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 230000017531 blood circulation Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 210000003802 sputum Anatomy 0.000 description 4
- 208000024794 sputum Diseases 0.000 description 4
- 206010041823 squamous cell carcinoma Diseases 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 206010047139 Vasoconstriction Diseases 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 210000004207 dermis Anatomy 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 210000002615 epidermis Anatomy 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000002085 irritant Substances 0.000 description 3
- 231100000021 irritant Toxicity 0.000 description 3
- 229960001528 oxymetazoline Drugs 0.000 description 3
- 230000010412 perfusion Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 210000005166 vasculature Anatomy 0.000 description 3
- 230000025033 vasoconstriction Effects 0.000 description 3
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010020565 Hyperaemia Diseases 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 208000022873 Ocular disease Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 2
- 206010039740 Screaming Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 239000000464 adrenergic agent Substances 0.000 description 2
- 235000013334 alcoholic beverage Nutrition 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000000843 anti-fungal effect Effects 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000036760 body temperature Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 235000019219 chocolate Nutrition 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 210000005069 ears Anatomy 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 208000030533 eye disease Diseases 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 210000004744 fore-foot Anatomy 0.000 description 2
- 235000012171 hot beverage Nutrition 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000005923 long-lasting effect Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- BDJRBEYXGGNYIS-UHFFFAOYSA-N nonanedioic acid Chemical compound OC(=O)CCCCCCCC(O)=O BDJRBEYXGGNYIS-UHFFFAOYSA-N 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000008326 skin blood flow Effects 0.000 description 2
- 235000021259 spicy food Nutrition 0.000 description 2
- 230000000475 sunscreen effect Effects 0.000 description 2
- 239000000516 sunscreening agent Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 210000002820 sympathetic nervous system Anatomy 0.000 description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 description 1
- FFTVPQUHLQBXQZ-KVUCHLLUSA-N (4s,4as,5ar,12ar)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O FFTVPQUHLQBXQZ-KVUCHLLUSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- ZKSGPMLZIPWJAF-ODZAUARKSA-N (z)-but-2-enedioic acid;oxalic acid Chemical compound OC(=O)C(O)=O.OC(=O)\C=C/C(O)=O ZKSGPMLZIPWJAF-ODZAUARKSA-N 0.000 description 1
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- AZSNMRSAGSSBNP-UHFFFAOYSA-N 22,23-dihydroavermectin B1a Natural products C1CC(C)C(C(C)CC)OC21OC(CC=C(C)C(OC1OC(C)C(OC3OC(C)C(O)C(OC)C3)C(OC)C1)C(C)C=CC=C1C3(C(C(=O)O4)C=C(C)C(O)C3OC1)O)CC4C2 AZSNMRSAGSSBNP-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- JHOJNZYPXCAPKL-UHFFFAOYSA-N 4-bromo-n-(4,5-dihydro-1h-imidazol-2-yl)-1h-benzimidazol-5-amine Chemical compound C1=CC=2NC=NC=2C(Br)=C1N=C1NCCN1 JHOJNZYPXCAPKL-UHFFFAOYSA-N 0.000 description 1
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
- SPBDXSGPUHCETR-JFUDTMANSA-N 8883yp2r6d Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O[C@@H]([C@@H](C)CC4)C(C)C)O3)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1C[C@H](C)[C@@H]([C@@H](C)CC)O[C@@]21O[C@H](C\C=C(C)\[C@@H](O[C@@H]1O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C1)[C@@H](C)\C=C\C=C/1[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\1)O)C[C@H]4C2 SPBDXSGPUHCETR-JFUDTMANSA-N 0.000 description 1
- 239000005660 Abamectin Substances 0.000 description 1
- 108060003345 Adrenergic Receptor Proteins 0.000 description 1
- 102000017910 Adrenergic receptor Human genes 0.000 description 1
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical class NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 1
- XYLJNLCSTIOKRM-UHFFFAOYSA-N Alphagan Chemical compound C1=CC2=NC=CN=C2C(Br)=C1NC1=NCCN1 XYLJNLCSTIOKRM-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 241000195940 Bryophyta Species 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
- 206010055665 Corneal neovascularisation Diseases 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- AERBNCYCJBRYDG-UHFFFAOYSA-N D-ribo-phytosphingosine Natural products CCCCCCCCCCCCCCC(O)C(O)C(N)CO AERBNCYCJBRYDG-UHFFFAOYSA-N 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- MQJKPEGWNLWLTK-UHFFFAOYSA-N Dapsone Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=C1 MQJKPEGWNLWLTK-UHFFFAOYSA-N 0.000 description 1
- 206010012455 Dermatitis exfoliative Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010014025 Ear swelling Diseases 0.000 description 1
- 239000001263 FEMA 3042 Substances 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 208000004454 Hyperalgesia Diseases 0.000 description 1
- 208000035154 Hyperesthesia Diseases 0.000 description 1
- SHGAZHPCJJPHSC-NUEINMDLSA-N Isotretinoin Chemical compound OC(=O)C=C(C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NUEINMDLSA-N 0.000 description 1
- 102000001399 Kallikrein Human genes 0.000 description 1
- 108060005987 Kallikrein Proteins 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 241000721454 Pemphigus Species 0.000 description 1
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 1
- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 1
- 238000011804 SKH1 hairless mouse Methods 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 229960002916 adapalene Drugs 0.000 description 1
- LZCDAPDGXCYOEH-UHFFFAOYSA-N adapalene Chemical compound C1=C(C(O)=O)C=CC2=CC(C3=CC=C(C(=C3)C34CC5CC(CC(C5)C3)C4)OC)=CC=C21 LZCDAPDGXCYOEH-UHFFFAOYSA-N 0.000 description 1
- 239000000695 adrenergic alpha-agonist Substances 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 102000004305 alpha Adrenergic Receptors Human genes 0.000 description 1
- 108090000861 alpha Adrenergic Receptors Proteins 0.000 description 1
- 102000030619 alpha-1 Adrenergic Receptor Human genes 0.000 description 1
- 108020004102 alpha-1 Adrenergic Receptor Proteins 0.000 description 1
- 102000030484 alpha-2 Adrenergic Receptor Human genes 0.000 description 1
- 108020004101 alpha-2 Adrenergic Receptor Proteins 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229960002684 aminocaproic acid Drugs 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 230000002141 anti-parasite Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229940124350 antibacterial drug Drugs 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- RRZXIRBKKLTSOM-XPNPUAGNSA-N avermectin B1a Chemical compound C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 RRZXIRBKKLTSOM-XPNPUAGNSA-N 0.000 description 1
- XNEFYCZVKIDDMS-UHFFFAOYSA-N avobenzone Chemical compound C1=CC(OC)=CC=C1C(=O)CC(=O)C1=CC=C(C(C)(C)C)C=C1 XNEFYCZVKIDDMS-UHFFFAOYSA-N 0.000 description 1
- 229960005193 avobenzone Drugs 0.000 description 1
- 229960002255 azelaic acid Drugs 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229960003679 brimonidine Drugs 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 229960004195 carvedilol Drugs 0.000 description 1
- NPAKNKYSJIDKMW-UHFFFAOYSA-N carvedilol Chemical compound COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=NC3=CC=C[CH]C3=C12 NPAKNKYSJIDKMW-UHFFFAOYSA-N 0.000 description 1
- 108060001132 cathelicidin Proteins 0.000 description 1
- 102000014509 cathelicidin Human genes 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 229960002227 clindamycin Drugs 0.000 description 1
- KDLRVYVGXIQJDK-AWPVFWJPSA-N clindamycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 KDLRVYVGXIQJDK-AWPVFWJPSA-N 0.000 description 1
- 229960002896 clonidine Drugs 0.000 description 1
- 201000000159 corneal neovascularization Diseases 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 229960000860 dapsone Drugs 0.000 description 1
- 239000000850 decongestant Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229960003722 doxycycline Drugs 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 208000004526 exfoliative dermatitis Diseases 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 238000005206 flow analysis Methods 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 229940013688 formic acid Drugs 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- LRBQNJMCXXYXIU-QWKBTXIPSA-N gallotannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@H]2[C@@H]([C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-QWKBTXIPSA-N 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960004275 glycolic acid Drugs 0.000 description 1
- 229940094952 green tea extract Drugs 0.000 description 1
- 235000020688 green tea extract Nutrition 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 1
- 229960005280 isotretinoin Drugs 0.000 description 1
- 229960002418 ivermectin Drugs 0.000 description 1
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
- 229960000282 metronidazole Drugs 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- FXWHFKOXMBTCMP-WMEDONTMSA-N milbemycin Natural products COC1C2OCC3=C/C=C/C(C)CC(=CCC4CC(CC5(O4)OC(C)C(C)C(OC(=O)C(C)CC(C)C)C5O)OC(=O)C(C=C1C)C23O)C FXWHFKOXMBTCMP-WMEDONTMSA-N 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 229960004023 minocycline Drugs 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 235000011929 mousse Nutrition 0.000 description 1
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
- VWPOSFSPZNDTMJ-UCWKZMIHSA-N nadolol Chemical compound C1[C@@H](O)[C@@H](O)CC2=C1C=CC=C2OCC(O)CNC(C)(C)C VWPOSFSPZNDTMJ-UCWKZMIHSA-N 0.000 description 1
- 229960004255 nadolol Drugs 0.000 description 1
- 210000002850 nasal mucosa Anatomy 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 230000037311 normal skin Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- AERBNCYCJBRYDG-KSZLIROESA-N phytosphingosine Chemical compound CCCCCCCCCCCCCC[C@@H](O)[C@@H](O)[C@@H](N)CO AERBNCYCJBRYDG-KSZLIROESA-N 0.000 description 1
- 229940033329 phytosphingosine Drugs 0.000 description 1
- KASDHRXLYQOAKZ-ZPSXYTITSA-N pimecrolimus Chemical compound C/C([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@@H](OC)C[C@@H](C)C/C(C)=C/[C@H](C(C[C@H](O)[C@H]1C)=O)CC)=C\[C@@H]1CC[C@@H](Cl)[C@H](OC)C1 KASDHRXLYQOAKZ-ZPSXYTITSA-N 0.000 description 1
- 229960005330 pimecrolimus Drugs 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 229960001285 quercetin Drugs 0.000 description 1
- 235000005875 quercetin Nutrition 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000006903 response to temperature Effects 0.000 description 1
- 235000021283 resveratrol Nutrition 0.000 description 1
- 229940016667 resveratrol Drugs 0.000 description 1
- 150000004492 retinoid derivatives Chemical class 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 108700022109 ropocamptide Proteins 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 229960000551 sulfacetamide sodium Drugs 0.000 description 1
- IHCDKJZZFOUARO-UHFFFAOYSA-M sulfacetamide sodium Chemical compound O.[Na+].CC(=O)[N-]S(=O)(=O)C1=CC=C(N)C=C1 IHCDKJZZFOUARO-UHFFFAOYSA-M 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229960001967 tacrolimus Drugs 0.000 description 1
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 239000003860 topical agent Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dermatology (AREA)
- Ophthalmology & Optometry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Cosmetics (AREA)
Abstract
Description
本出願は、その全ての開示内容が参照によって本願に組み込まれる、2011年11月10日に出願された米国特許仮出願番号第61/558,104号の利点を主張するものである。
抗菌薬(抗寄生虫性、抗菌性の、抗真菌性、抗ウイルス性など);
メトロニダゾール、イベルメクチン、クリンダマイシン、エリスロマイシン、テトラサイクリン、ドキシサイクリン、ミノサイクリン;
ステロイド系および非ステロイド系抗炎症剤(コルチコステロイド、タクロリムス、ピメクロリムス、シクロスポリンAなど);
抗血管新生剤;
抗抗酸菌剤(ダプソンなど);
サンスクリーンまたはサンブロックまたはサンスクリーン/サンブロックのような機能を持つもの(二酸化チタン、酸化亜鉛、アヴォベンゾンなど);
酸化防止剤(ビタミンC、E、ケルセチン、レスベラトロルなど);
その他α‐作動薬(ブリモニジン、オキシメタゾリン、クロニジンなど);
βブロッカー(ナドロール、プロプラノロール、カルベジロールなど);
抗ヒスタミン薬;
レチノイド(トレチノイン、アダパレン、タゾロテン、イソトレチノイン、レチノアルデヒドなど);
過酸化ベンゾイル;
メントールおよびその他の「冷感」剤;
スルファセタミドナトリウム;
抗真菌薬(イミダゾール誘導体、ポリエン化合物、アリルアミン化合物など);
セリンプロテアーゼ(カリクレイン)阻害剤(アミノカプロン酸など)。
ラットの血流分析
背景
酒さは熱への暴露によって引き起こされる。生理的交感神経系を介した身体冷却への応答は、皮膚血管収縮であり、身体加温への応答は皮膚血管拡張である。交感神経系の流出に作用するα‐アドレナリン作動薬は、温度変化に応答して皮膚の血流を調節する。
後足の肉球の微小血管赤血球のかん流を観測するため、レーザードップラー微小血管かん流モニター(レーザードップラー流量測定技術:LDP)が用いられた。レーザードップラー流量計(LDP)は Oxford Optronix LTd.(英国)製のOxyFlo Microvascular Perfusion Monitorを用いた。
体外でのヒトの皮膚に対する浸透性分析
ヒトの胴体の外部皮膚をわずか2cm2のフランツ分散セルにピッタリ入れるのに十分な大きさを有する複数の部分に切り分けた。真皮受け入れコンパートメントに0.1Xリン酸緩衝溶液で構成される受容体溶液を0.1%オレス(Oleth)−20と共にその容積一杯に満たして、表皮チェンバー(チムニー)を実験室内の空気に露出したままにしておく。それらのセルをそれらのセルを分散装置内に入れ、その装置内で、真皮の下側と接触している受容体溶液を約600rpmの回転速度で磁力によって撹拌し、その温度は皮膚の表面温度が32.0±1.0℃となるように維持された。
LL−37に誘発された肌の炎症マウスモデル
背景
酒さ肌は、通常の肌と比較して、LL−37カテリシジンのレベルが高いことと関連している。マウスへのLL−37の皮内注射は、酒さ肌に見られるものに似た肌の炎症を引き起こす(Yamasaki 2007)。
(S)−(+)−7−(1H−イミダゾール−4−イルメチル)−5,6,7,8−テトラヒドロキノリンゲルまたはその対応するビヒクルが、BALB/cマウスの耳の後表面に塗布された。塗布の1時間後、左耳にはLL−37ペプチドを皮内注射し、右耳にはリン酸緩衝生理食塩水(PBS)を注射した。耳の厚み測定が、デジタルキャリパー(Mitutoyo製)を用いてLL−37注射の8時間までの各時点でなされた。耳の腫れは炎症の指標である。
紫外線Bに誘発されたマウスの日焼けモデル
背景
酒さは紫外(UV)光への暴露によって引き起こされうる。無毛マウスのUVB照射への暴露は、紅斑、皮膚血管拡張、触覚過敏および少なくとも48時間続く炎症に特徴づけられる、日焼けに似た応答をもたらす。
方法
Claims (15)
- 肌の状態を患う患者について肌の状態を治療する方法であって、治療上有効な量の7−(1H−イミダゾール−4−イルメチル)−5,6,7,8−テトラヒドロキノリン、その各光学異性体もしくはその各互変異性体、またはそれらの薬学的に許容される塩を含む医薬組成物によって前記患者を治療することを含む方法。
- 前記医薬組成物は、(R)−(−)−7−(1H−イミダゾール−4−イルメチル)−5,6,7,8−テトラヒドロキノリンを含む、請求項1に記載の方法。
- 前記医薬組成物は、(S)−(+)−7−(1H−イミダゾール−4−イルメチル)−5,6,7,8−テトラヒドロキノリンを含む、請求項1に記載の方法。
- 治療される状態は、酒さ、劇症酒さ、日焼け、乾癬、閉経に関連した顔面潮紅、顔面潮紅に関連した潮紅および発赤、顔面潮紅に関連した紅斑、睾丸切除に由来するアトピー性皮膚炎による顔面潮紅、虫刺されによる発赤およびかゆみの治療、光老化、脂漏性皮膚炎、ざ瘡、アレルギー性皮膚炎、顔面の毛細管拡張症(以前から存在していた毛細血管の膨張)、血管拡張症、酒さ鼻(小胞膨張による鼻の異常肥大)、ざ瘡状皮疹(にじみ出たり固くなったりする)、灼熱感や刺激感、肌の紅斑、皮膚血管の膨張を伴う皮下の機能昂進、ライエル症候群、スティーブン・ジョンソン症候群、痔に関連した局所的掻痒または不快感、痔、軽症型多形紅斑、重症型多形紅斑、結節性紅斑、目の周りのむくみ、じんましん、心因性掻痒症(pruritis)、紫斑病、静脈瘤、接触性皮膚炎、アトピー性皮膚炎、貨幣状皮膚炎、全身性剥脱性皮膚炎、鬱滞性皮膚炎、慢性単純性苔癬、口囲皮膚炎、髭の偽性毛嚢炎、環状肉芽腫、光線角化症、基底細胞がん、扁平上皮細胞がん、および湿疹から選択される、請求項1に記載の方法。
- 前記状態は酒さである、請求項1に記載の方法。
- 前記状態は乾癬である、請求項1に記載の方法。
- 前記状態は劇症酒さである、請求項1に記載の方法。
- 前記状態は顔面の毛細管拡張症である、請求項1に記載の方法。
- 前記状態は肌の紅斑である、請求項1に記載の方法。
- 前記医薬組成物は、局所皮膚外用剤、懸濁液、ゲル、溶液、クリーム、ローション、軟膏、フォーム、乳濁液、ミクロ乳濁液、乳液、美容液、エアロゾル、スプレー、分散液、マイクロカプセル、ベシクル、微小粒子、濡れた布、乾燥した布、顔面用の布、または直接注射剤として適した製剤中にある、請求項1に記載の方法。
- 包装材と前記包装材内部に含まれる医薬品を含む製造品で、前記医薬品が皮膚状態の治療にあたり治療上有効であり、前記包装材は前記医薬品が皮膚状態を治療するために用いることができることを示すラベルを含み、前記医薬品は治療上有効量の7−(1H−イミダゾール−4−イルメチル)−5,6,7,8−テトラヒドロキノリンまたはその光学異性体を含む、製造品。
- 前記医薬品は治療上有効量の(S)−(+)−7−(1H−イミダゾール−4−イルメチル)−5,6,7,8−テトラヒドロキノリンを含む、請求項11に記載の製造品。
- 眼酒さ、翼状片または結膜充血を患う患者について眼酒さ、翼状片または結膜充血を治療する方法であって、治療上有効量の7−(1H−イミダゾール−4−イルメチル)−5,6,7,8−テトラヒドロキノリン、その各光学異性体もしくはその各互変異性体、またはそれらの薬学的に許容される塩を含む医薬組成物によって前記患者を治療することを含む方法。
- 前記医薬組成物は、(R)−(−)−7−(1H−イミダゾール−4−イルメチル)−5,6,7,8−テトラヒドロキノリンを含む、請求項13に記載の方法。
- 前記医薬組成物は、(S)−(+)−7−(1H−イミダゾール−4−イルメチル)−5,6,7,8−テトラヒドロキノリンを含む、請求項13に記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201161558104P | 2011-11-10 | 2011-11-10 | |
US61/558,104 | 2011-11-10 | ||
PCT/US2012/064075 WO2013070861A1 (en) | 2011-11-10 | 2012-11-08 | Pharmaceutical compositions comprising 7-(1h-imidazol-4-ylmethyl)-5,6,7,8-tetrahydro-quinoline for treating skin diseases and conditions |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017092572A Division JP6526737B2 (ja) | 2011-11-10 | 2017-05-08 | 7−(1h−イミダゾール−4−イルメチル)−5,6,7,8−テトラヒドロキノリンを含む肌の疾患および状態を治療するための医薬組成物 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2014533271A true JP2014533271A (ja) | 2014-12-11 |
JP2014533271A5 JP2014533271A5 (ja) | 2016-01-07 |
JP6359456B2 JP6359456B2 (ja) | 2018-07-18 |
Family
ID=47178364
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014541225A Active JP6359456B2 (ja) | 2011-11-10 | 2012-11-08 | 7−(1h−イミダゾール−4−イルメチル)−5,6,7,8−テトラヒドロキノリンを含む肌の疾患および状態を治療するための医薬組成物 |
JP2017092572A Active JP6526737B2 (ja) | 2011-11-10 | 2017-05-08 | 7−(1h−イミダゾール−4−イルメチル)−5,6,7,8−テトラヒドロキノリンを含む肌の疾患および状態を治療するための医薬組成物 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017092572A Active JP6526737B2 (ja) | 2011-11-10 | 2017-05-08 | 7−(1h−イミダゾール−4−イルメチル)−5,6,7,8−テトラヒドロキノリンを含む肌の疾患および状態を治療するための医薬組成物 |
Country Status (21)
Country | Link |
---|---|
US (4) | US20130123303A1 (ja) |
EP (3) | EP2776034B1 (ja) |
JP (2) | JP6359456B2 (ja) |
KR (1) | KR102004563B1 (ja) |
CN (1) | CN104136029A (ja) |
AR (1) | AR088845A1 (ja) |
AU (2) | AU2012335803B2 (ja) |
BR (1) | BR112014011336A2 (ja) |
CA (1) | CA2855005C (ja) |
CL (1) | CL2014001242A1 (ja) |
DK (1) | DK2776034T3 (ja) |
ES (1) | ES2635421T3 (ja) |
IL (3) | IL232483B (ja) |
MX (1) | MX350662B (ja) |
MY (1) | MY182553A (ja) |
RU (2) | RU2630978C2 (ja) |
SG (3) | SG10201809506TA (ja) |
TW (3) | TWI580424B (ja) |
UA (1) | UA109359C2 (ja) |
WO (1) | WO2013070861A1 (ja) |
ZA (1) | ZA201403396B (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020504178A (ja) * | 2017-01-04 | 2020-02-06 | ピエール、ファブレ、デルモ‐コスメティークPierre Fabre Dermo−Cosmetique | 酒さを処置するためのポンガミア油と4−t−ブチルシクロヘキサノールの組合せを含んでなる化粧用組成物 |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9283217B2 (en) | 2011-11-10 | 2016-03-15 | Allergan, Inc. | Pharmaceutical compositions comprising 7-(1 H-imidazol-4-ylmethyl)-5,6,7,8-tetrahydro-quinoline for treating skin diseases and conditions |
SG11201509173WA (en) * | 2013-05-06 | 2015-12-30 | Allergan Inc | Alpha adrenergic agonists for in the treatment of tissue trauma |
RU2727695C1 (ru) * | 2020-02-13 | 2020-07-22 | Мурад Умарович Магомедов | Способ комплексного лечения ринофимы |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008500356A (ja) * | 2004-05-25 | 2008-01-10 | サンズローザ ファーマシューティカル ディヴェロップメント インコーポレイテッド | 炎症性皮膚疾患を治療又は予防するための化合物、製剤及び方法 |
US7323477B2 (en) * | 2006-02-02 | 2008-01-29 | Allergan, Inc. | 7-((1H-imidazol-4-yl)methyl)-5,6,7,8-tetrahydroquinoline |
WO2010092312A1 (fr) * | 2009-02-16 | 2010-08-19 | Galderma Research & Development | Association d' avermectines ou mylbemycines avec des récepteurs adrénergiques pour le traitement ou la prévention des affections dermatologiques |
JP2010537988A (ja) * | 2007-08-31 | 2010-12-09 | ガルデマ ラボラトリーズ インコーポレイテッド | 紅斑を治療するための改良ブリモニジン組成物 |
WO2011053487A1 (en) * | 2009-10-26 | 2011-05-05 | Galderma Pharma S.A. | Methods of treating or preventing acute erythema |
WO2011075617A1 (en) * | 2009-12-17 | 2011-06-23 | Alpha Synergy Development, Inc. | Compositions and methods for eye whitening |
WO2011075267A1 (en) * | 2009-11-19 | 2011-06-23 | Galderma Laboratories Lp | Use of alpha 2 adrenergic receptor agonists for treating or preventing psoriasis |
WO2011117377A2 (en) * | 2010-03-26 | 2011-09-29 | Galderma Research & Development | Improved methods and compositions for safe and effective treatment of erythema |
WO2011117378A2 (en) * | 2010-03-26 | 2011-09-29 | Galderma Research & Development | Improved methods and compositions for safe and effective treatment of telangiectasia |
Family Cites Families (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6455583B1 (en) * | 1998-05-08 | 2002-09-24 | The University Of Miami | Method for treating meibomian gland disease |
US6242442B1 (en) * | 1998-12-17 | 2001-06-05 | Alcon Laboratories, Inc. | Brinzolamide and brimonidine for treating ocular conditions |
US20010049369A1 (en) * | 2000-02-10 | 2001-12-06 | Jablonski Monica M. | Brimonidine compositions and methods for retinal degeneration |
US6468989B1 (en) | 2000-07-13 | 2002-10-22 | Dow Pharmaceutical Sciences | Gel compositions containing metronidazole |
US6387383B1 (en) | 2000-08-03 | 2002-05-14 | Dow Pharmaceutical Sciences | Topical low-viscosity gel composition |
US20020198209A1 (en) | 2001-05-03 | 2002-12-26 | Allergan Sales Inc. | Compositions having enhanced pharmacokinetic characteristics |
US6680062B2 (en) | 2001-10-05 | 2004-01-20 | Color Access, Inc. | Anti-irritating rosacea treatment |
US7030149B2 (en) * | 2002-04-19 | 2006-04-18 | Allergan, Inc. | Combination of brimonidine timolol for topical ophthalmic use |
US20040146539A1 (en) * | 2003-01-24 | 2004-07-29 | Gupta Shyam K. | Topical Nutraceutical Compositions with Selective Body Slimming and Tone Firming Antiaging Benefits |
US7439241B2 (en) * | 2003-05-27 | 2008-10-21 | Galderma Laboratories, Inc. | Compounds, formulations, and methods for treating or preventing rosacea |
US20050020600A1 (en) * | 2003-07-23 | 2005-01-27 | Scherer Warren J. | Methods of treating cutaneous flushing using selective alpha-2-adrenergic receptor agonists |
US20050130906A1 (en) * | 2003-11-20 | 2005-06-16 | Matier William L. | Amelioration of macular degeneration and other ophthalmic diseases |
US7812049B2 (en) | 2004-01-22 | 2010-10-12 | Vicept Therapeutics, Inc. | Method and therapeutic/cosmetic topical compositions for the treatment of rosacea and skin erythema using α1-adrenoceptor agonists |
US20070203144A1 (en) * | 2006-01-17 | 2007-08-30 | Allergan, Inc. | Use of Memantine and Brimonidine to Attenuate Vitreoretinal Vascular Endothelial Growth Factor (VEGF) Protein Levels in Animals |
RU2321399C1 (ru) * | 2006-06-01 | 2008-04-10 | Федеральное государственное учреждение "Нижегородский научно-исследовательский кожно-венерологический институт Федерального агентства по здравоохранению и социальному развитию" | Способ лечения больных розацеа |
WO2008124151A2 (en) * | 2007-04-09 | 2008-10-16 | Avicena Group, Inc. | Use of creatine compounds for the treatment of eye disorders |
US8455548B2 (en) | 2007-10-18 | 2013-06-04 | Allergan, Inc. | Method of treating sensorimotor disorders with alpha-2 adrenergic receptor agonists |
US20100029662A1 (en) * | 2008-08-01 | 2010-02-04 | Alpha Synergy Development, Inc. | Vasoconstriction compositions and methods of use |
AU2011287544B2 (en) * | 2010-08-06 | 2014-12-11 | Galderma Research & Development | Combination of compounds for treating or preventing skin diseases |
-
2012
- 2012-08-11 UA UAA201406109A patent/UA109359C2/ru unknown
- 2012-11-08 CA CA2855005A patent/CA2855005C/en active Active
- 2012-11-08 MY MYPI2014001376A patent/MY182553A/en unknown
- 2012-11-08 EP EP12784857.0A patent/EP2776034B1/en active Active
- 2012-11-08 US US13/672,475 patent/US20130123303A1/en not_active Abandoned
- 2012-11-08 DK DK12784857.0T patent/DK2776034T3/en active
- 2012-11-08 AU AU2012335803A patent/AU2012335803B2/en active Active
- 2012-11-08 RU RU2014122758A patent/RU2630978C2/ru active
- 2012-11-08 EP EP20193075.7A patent/EP3763370A1/en not_active Withdrawn
- 2012-11-08 BR BR112014011336A patent/BR112014011336A2/pt not_active Application Discontinuation
- 2012-11-08 EP EP17156230.9A patent/EP3184110B1/en active Active
- 2012-11-08 WO PCT/US2012/064075 patent/WO2013070861A1/en active Application Filing
- 2012-11-08 ES ES12784857.0T patent/ES2635421T3/es active Active
- 2012-11-08 KR KR1020147015533A patent/KR102004563B1/ko active IP Right Grant
- 2012-11-08 MX MX2014005640A patent/MX350662B/es active IP Right Grant
- 2012-11-08 SG SG10201809506TA patent/SG10201809506TA/en unknown
- 2012-11-08 RU RU2017131492A patent/RU2667645C1/ru active
- 2012-11-08 SG SG11201402246RA patent/SG11201402246RA/en unknown
- 2012-11-08 SG SG10201609145PA patent/SG10201609145PA/en unknown
- 2012-11-08 CN CN201280065945.0A patent/CN104136029A/zh active Pending
- 2012-11-08 JP JP2014541225A patent/JP6359456B2/ja active Active
- 2012-11-09 TW TW101141967A patent/TWI580424B/zh active
- 2012-11-09 TW TW108123351A patent/TW202014189A/zh unknown
- 2012-11-09 TW TW106103338A patent/TWI708604B/zh active
- 2012-11-12 AR ARP120104260A patent/AR088845A1/es unknown
-
2014
- 2014-05-07 IL IL232483A patent/IL232483B/en active IP Right Grant
- 2014-05-12 CL CL2014001242A patent/CL2014001242A1/es unknown
- 2014-05-12 ZA ZA2014/03396A patent/ZA201403396B/en unknown
-
2015
- 2015-05-01 US US14/702,219 patent/US9308201B2/en active Active
- 2015-10-30 US US14/927,948 patent/US20160051534A1/en not_active Abandoned
-
2016
- 2016-08-17 AU AU2016216627A patent/AU2016216627B2/en active Active
- 2016-11-16 US US15/353,262 patent/US20170095466A1/en not_active Abandoned
-
2017
- 2017-05-08 JP JP2017092572A patent/JP6526737B2/ja active Active
-
2018
- 2018-08-21 IL IL261269A patent/IL261269A/en unknown
-
2019
- 2019-08-18 IL IL26875719A patent/IL268757A/en unknown
Patent Citations (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008500356A (ja) * | 2004-05-25 | 2008-01-10 | サンズローザ ファーマシューティカル ディヴェロップメント インコーポレイテッド | 炎症性皮膚疾患を治療又は予防するための化合物、製剤及び方法 |
US7323477B2 (en) * | 2006-02-02 | 2008-01-29 | Allergan, Inc. | 7-((1H-imidazol-4-yl)methyl)-5,6,7,8-tetrahydroquinoline |
JP2010537988A (ja) * | 2007-08-31 | 2010-12-09 | ガルデマ ラボラトリーズ インコーポレイテッド | 紅斑を治療するための改良ブリモニジン組成物 |
JP2012517989A (ja) * | 2009-02-16 | 2012-08-09 | ガルデルマ・リサーチ・アンド・デヴェロップメント | 皮膚疾患を治療または予防するための、アベルメクチンまたはミルベマイシンとアドレナリン受容体との組合せ |
WO2010092312A1 (fr) * | 2009-02-16 | 2010-08-19 | Galderma Research & Development | Association d' avermectines ou mylbemycines avec des récepteurs adrénergiques pour le traitement ou la prévention des affections dermatologiques |
WO2011053487A1 (en) * | 2009-10-26 | 2011-05-05 | Galderma Pharma S.A. | Methods of treating or preventing acute erythema |
JP2013508454A (ja) * | 2009-10-26 | 2013-03-07 | ガルデルマ ファルマ ソシエテ アノニム | 急性紅斑の治療又は予防法 |
WO2011075267A1 (en) * | 2009-11-19 | 2011-06-23 | Galderma Laboratories Lp | Use of alpha 2 adrenergic receptor agonists for treating or preventing psoriasis |
JP2013511534A (ja) * | 2009-11-19 | 2013-04-04 | ガルデルマ・ラボラトリーズ・エルピー | 乾癬を治療または予防するためのα2アドレナリン受容体作動薬の使用 |
WO2011075617A1 (en) * | 2009-12-17 | 2011-06-23 | Alpha Synergy Development, Inc. | Compositions and methods for eye whitening |
JP2013514985A (ja) * | 2009-12-17 | 2013-05-02 | アルフア・シナジー・デイベロプメント・インコーポレイテツド | 眼のホワイトニングのための組成物および方法 |
WO2011117377A2 (en) * | 2010-03-26 | 2011-09-29 | Galderma Research & Development | Improved methods and compositions for safe and effective treatment of erythema |
WO2011117378A2 (en) * | 2010-03-26 | 2011-09-29 | Galderma Research & Development | Improved methods and compositions for safe and effective treatment of telangiectasia |
JP2013523612A (ja) * | 2010-03-26 | 2013-06-17 | ガルデルマ・リサーチ・アンド・デヴェロップメント | 毛細血管拡張症の安全かつ有効な治療のための改善された方法および組成物 |
JP2013523611A (ja) * | 2010-03-26 | 2013-06-17 | ガルデルマ・リサーチ・アンド・デヴェロップメント | 紅斑の安全かつ有効な治療のための改善された方法および組成物 |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020504178A (ja) * | 2017-01-04 | 2020-02-06 | ピエール、ファブレ、デルモ‐コスメティークPierre Fabre Dermo−Cosmetique | 酒さを処置するためのポンガミア油と4−t−ブチルシクロヘキサノールの組合せを含んでなる化粧用組成物 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6526737B2 (ja) | 7−(1h−イミダゾール−4−イルメチル)−5,6,7,8−テトラヒドロキノリンを含む肌の疾患および状態を治療するための医薬組成物 | |
US10201535B2 (en) | Pharmaceutical compositions comprising 7-(1H-imidazol-4-ylmethyl)-5,6,7,8-tetrahydro-quinoline for treating skin diseases and conditions | |
US20140235685A1 (en) | Pharmaceutical compositions comprising 4-bromo-n-(imidazolidin-2-ylidene)-1h-benzimidazol-5-amine for treating skin diseases | |
NZ624771B2 (en) | Pharmaceutical compositions comprising 7-(1h-imidazol-4-ylmethyl)-5,6,7,8-tetrahydro-quinoline for treating skin diseases and conditions | |
US9889126B2 (en) | Use of naratriptan in the treatment of rosacea |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20151109 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20151109 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160824 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20160826 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20161124 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20170104 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180411 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20180620 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6359456 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |