CN1196506C - 带有改进的喷雾几何形状的鼻子喷雾装置 - Google Patents
带有改进的喷雾几何形状的鼻子喷雾装置 Download PDFInfo
- Publication number
- CN1196506C CN1196506C CNB998046493A CN99804649A CN1196506C CN 1196506 C CN1196506 C CN 1196506C CN B998046493 A CNB998046493 A CN B998046493A CN 99804649 A CN99804649 A CN 99804649A CN 1196506 C CN1196506 C CN 1196506C
- Authority
- CN
- China
- Prior art keywords
- fluid
- straight line
- line portion
- spraying
- spray
- 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.)
- Expired - Fee Related
Links
- 239000007921 spray Substances 0.000 title claims abstract description 24
- 229940097496 nasal spray Drugs 0.000 title description 3
- 239000007922 nasal spray Substances 0.000 title description 3
- 239000012530 fluid Substances 0.000 claims abstract description 58
- 238000005507 spraying Methods 0.000 claims abstract description 45
- 241000158526 Nasalis Species 0.000 claims description 36
- 239000003814 drug Substances 0.000 claims description 28
- 239000000203 mixture Substances 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 15
- 210000001944 turbinate Anatomy 0.000 claims description 11
- 239000004094 surface-active agent Substances 0.000 claims description 6
- 238000009792 diffusion process Methods 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 4
- 235000013599 spices Nutrition 0.000 claims description 2
- 210000003928 nasal cavity Anatomy 0.000 abstract description 16
- 238000000034 method Methods 0.000 abstract description 6
- 239000003795 chemical substances by application Substances 0.000 abstract description 4
- 210000003041 ligament Anatomy 0.000 abstract description 3
- 230000035515 penetration Effects 0.000 abstract 1
- 239000007788 liquid Substances 0.000 description 25
- 210000001331 nose Anatomy 0.000 description 20
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 15
- -1 tetrahydrazoline Chemical compound 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 238000002347 injection Methods 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 230000001387 anti-histamine Effects 0.000 description 8
- 239000000739 antihistaminic agent Substances 0.000 description 8
- 239000002245 particle Substances 0.000 description 7
- 238000007789 sealing Methods 0.000 description 7
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 229920001971 elastomer Polymers 0.000 description 5
- 239000000806 elastomer Substances 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000003755 preservative agent Substances 0.000 description 5
- 239000002562 thickening agent Substances 0.000 description 5
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 4
- HUCJFAOMUPXHDK-UHFFFAOYSA-N Xylometazoline Chemical compound CC1=CC(C(C)(C)C)=CC(C)=C1CC1=NCCN1 HUCJFAOMUPXHDK-UHFFFAOYSA-N 0.000 description 4
- 239000000850 decongestant Substances 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 210000003128 head Anatomy 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 239000002260 anti-inflammatory agent Substances 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 229960003291 chlorphenamine Drugs 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 230000005684 electric field Effects 0.000 description 3
- 210000000981 epithelium Anatomy 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- WTEVQBCEXWBHNA-JXMROGBWSA-N geranial Chemical compound CC(C)=CCC\C(C)=C\C=O WTEVQBCEXWBHNA-JXMROGBWSA-N 0.000 description 3
- 238000009413 insulation Methods 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 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 3
- 239000000080 wetting agent Substances 0.000 description 3
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 2
- CNIIGCLFLJGOGP-UHFFFAOYSA-N 2-(1-naphthalenylmethyl)-4,5-dihydro-1H-imidazole Chemical compound C=1C=CC2=CC=CC=C2C=1CC1=NCCN1 CNIIGCLFLJGOGP-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- 206010002198 Anaphylactic reaction Diseases 0.000 description 2
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical compound C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- WTEVQBCEXWBHNA-UHFFFAOYSA-N Citral Natural products CC(C)=CCCC(C)=CC=O WTEVQBCEXWBHNA-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- WJOHZNCJWYWUJD-IUGZLZTKSA-N Fluocinonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)COC(=O)C)[C@@]2(C)C[C@@H]1O WJOHZNCJWYWUJD-IUGZLZTKSA-N 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 239000008896 Opium Substances 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- ZZHLYYDVIOPZBE-UHFFFAOYSA-N Trimeprazine Chemical compound C1=CC=C2N(CC(CN(C)C)C)C3=CC=CC=C3SC2=C1 ZZHLYYDVIOPZBE-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 230000036783 anaphylactic response Effects 0.000 description 2
- 208000003455 anaphylaxis Diseases 0.000 description 2
- 229940124599 anti-inflammatory drug Drugs 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 239000010238 camphora Substances 0.000 description 2
- 229940025250 camphora Drugs 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 235000020971 citrus fruits Nutrition 0.000 description 2
- KSMVZQYAVGTKIV-UHFFFAOYSA-N decanal Chemical compound CCCCCCCCCC=O KSMVZQYAVGTKIV-UHFFFAOYSA-N 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 229960000785 fluocinonide Drugs 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 210000003630 histaminocyte Anatomy 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 238000001746 injection moulding Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 229960004305 lodoxamide Drugs 0.000 description 2
- RVGLGHVJXCETIO-UHFFFAOYSA-N lodoxamide Chemical compound OC(=O)C(=O)NC1=CC(C#N)=CC(NC(=O)C(O)=O)=C1Cl RVGLGHVJXCETIO-UHFFFAOYSA-N 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 229960001027 opium Drugs 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920001296 polysiloxane Polymers 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000002787 reinforcement Effects 0.000 description 2
- 210000000582 semen Anatomy 0.000 description 2
- 229920002379 silicone rubber Polymers 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 229920003048 styrene butadiene rubber Polymers 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 229920002725 thermoplastic elastomer Polymers 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- MDYZKJNTKZIUSK-UHFFFAOYSA-N tyloxapol Chemical compound O=C.C1CO1.CC(C)(C)CC(C)(C)C1=CC=C(O)C=C1 MDYZKJNTKZIUSK-UHFFFAOYSA-N 0.000 description 2
- 229960000833 xylometazoline Drugs 0.000 description 2
- YHQGMYUVUMAZJR-UHFFFAOYSA-N α-terpinene Chemical compound CC(C)C1=CC=C(C)CC1 YHQGMYUVUMAZJR-UHFFFAOYSA-N 0.000 description 2
- RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 description 1
- FCGXLCNBWYIEAA-UHFFFAOYSA-N 1,3-benzothiazol-6-ylmethanamine Chemical compound NCC1=CC=C2N=CSC2=C1 FCGXLCNBWYIEAA-UHFFFAOYSA-N 0.000 description 1
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
- CBOBADCVMLMQRW-UHFFFAOYSA-N 2,6-dimethyloctanal Chemical compound CCC(C)CCCC(C)C=O CBOBADCVMLMQRW-UHFFFAOYSA-N 0.000 description 1
- XSXWOBXNYNULJG-UHFFFAOYSA-N 2-(2,4,4-trimethylpentan-2-yl)phenol Chemical compound CC(C)(C)CC(C)(C)C1=CC=CC=C1O XSXWOBXNYNULJG-UHFFFAOYSA-N 0.000 description 1
- DPPDPATYPQFYDL-UHFFFAOYSA-N 2-[2-(dimethylamino)ethyl]-4-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepine-5-thione Chemical compound O1C(CCN(C)C)CN(C)C(=S)C2=CC=CN=C21 DPPDPATYPQFYDL-UHFFFAOYSA-N 0.000 description 1
- OIALAIQRYISUEV-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]e Polymers CCCCCCCCCCCCCCCCCC(=O)OCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO OIALAIQRYISUEV-UHFFFAOYSA-N 0.000 description 1
- SPCKHVPPRJWQRZ-UHFFFAOYSA-N 2-benzhydryloxy-n,n-dimethylethanamine;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 SPCKHVPPRJWQRZ-UHFFFAOYSA-N 0.000 description 1
- LXAHHHIGZXPRKQ-UHFFFAOYSA-N 5-fluoro-2-methylpyridine Chemical compound CC1=CC=C(F)C=N1 LXAHHHIGZXPRKQ-UHFFFAOYSA-N 0.000 description 1
- JTOUASWUIMAMAD-UHFFFAOYSA-N 7-[2-hydroxy-3-[4-(3-phenylsulfanylpropyl)piperazin-1-yl]propyl]-1,3-dimethylpurine-2,6-dione Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2N=CN1CC(O)CN(CC1)CCN1CCCSC1=CC=CC=C1 JTOUASWUIMAMAD-UHFFFAOYSA-N 0.000 description 1
- PFWLFWPASULGAN-UHFFFAOYSA-N 7-methylxanthine Chemical compound N1C(=O)NC(=O)C2=C1N=CN2C PFWLFWPASULGAN-UHFFFAOYSA-N 0.000 description 1
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- MBUVEWMHONZEQD-UHFFFAOYSA-N Azeptin Chemical compound C1CN(C)CCCC1N1C(=O)C2=CC=CC=C2C(CC=2C=CC(Cl)=CC=2)=N1 MBUVEWMHONZEQD-UHFFFAOYSA-N 0.000 description 1
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 241000207199 Citrus Species 0.000 description 1
- 244000183685 Citrus aurantium Species 0.000 description 1
- 235000007716 Citrus aurantium Nutrition 0.000 description 1
- 235000000228 Citrus myrtifolia Nutrition 0.000 description 1
- 241001672694 Citrus reticulata Species 0.000 description 1
- 235000016646 Citrus taiwanica Nutrition 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 235000016936 Dendrocalamus strictus Nutrition 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
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- WEEGYLXZBRQIMU-UHFFFAOYSA-N Eucalyptol Chemical compound C1CC2CCC1(C)OC2(C)C WEEGYLXZBRQIMU-UHFFFAOYSA-N 0.000 description 1
- 244000153234 Hibiscus abelmoschus Species 0.000 description 1
- 229940124056 Histamine H1 receptor antagonist Drugs 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 description 1
- ZCVMWBYGMWKGHF-UHFFFAOYSA-N Ketotifene Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2CC(=O)C2=C1C=CS2 ZCVMWBYGMWKGHF-UHFFFAOYSA-N 0.000 description 1
- 102000003820 Lipoxygenases Human genes 0.000 description 1
- 108090000128 Lipoxygenases Proteins 0.000 description 1
- OCJYIGYOJCODJL-UHFFFAOYSA-N Meclizine Chemical compound CC1=CC=CC(CN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC(Cl)=CC=2)=C1 OCJYIGYOJCODJL-UHFFFAOYSA-N 0.000 description 1
- HOKDBMAJZXIPGC-UHFFFAOYSA-N Mequitazine Chemical compound C12=CC=CC=C2SC2=CC=CC=C2N1CC1C(CC2)CCN2C1 HOKDBMAJZXIPGC-UHFFFAOYSA-N 0.000 description 1
- 229920003091 Methocel™ Polymers 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 206010028735 Nasal congestion Diseases 0.000 description 1
- ISFHAYSTHMVOJR-UHFFFAOYSA-N Phenindamine Chemical compound C1N(C)CCC(C2=CC=CC=C22)=C1C2C1=CC=CC=C1 ISFHAYSTHMVOJR-UHFFFAOYSA-N 0.000 description 1
- 241000283216 Phocidae Species 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 239000002174 Styrene-butadiene Substances 0.000 description 1
- OGEAASSLWZDQBM-UHFFFAOYSA-N Temelastine Chemical compound C1=NC(C)=CC=C1CC(C(N1)=O)=CN=C1NCCCCC1=NC=C(Br)C=C1C OGEAASSLWZDQBM-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- UFLGIAIHIAPJJC-UHFFFAOYSA-N Tripelennamine Chemical compound C=1C=CC=NC=1N(CCN(C)C)CC1=CC=CC=C1 UFLGIAIHIAPJJC-UHFFFAOYSA-N 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 229960003792 acrivastine Drugs 0.000 description 1
- PWACSDKDOHSSQD-IUTFFREVSA-N acrivastine Chemical compound C1=CC(C)=CC=C1C(\C=1N=C(\C=C\C(O)=O)C=CC=1)=C/CN1CCCC1 PWACSDKDOHSSQD-IUTFFREVSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229960003790 alimemazine Drugs 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 229940124623 antihistamine drug Drugs 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- GXDALQBWZGODGZ-UHFFFAOYSA-N astemizole Chemical compound C1=CC(OC)=CC=C1CCN1CCC(NC=2N(C3=CC=CC=C3N=2)CC=2C=CC(F)=CC=2)CC1 GXDALQBWZGODGZ-UHFFFAOYSA-N 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 229960000383 azatadine Drugs 0.000 description 1
- SEBMTIQKRHYNIT-UHFFFAOYSA-N azatadine Chemical compound C1CN(C)CCC1=C1C2=NC=CC=C2CCC2=CC=CC=C21 SEBMTIQKRHYNIT-UHFFFAOYSA-N 0.000 description 1
- 229960004574 azelastine Drugs 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 229940038482 beclomethasone dipropionate monohydrate Drugs 0.000 description 1
- YNKMHABLMGIIFX-UHFFFAOYSA-N benzaldehyde;methane Chemical compound C.O=CC1=CC=CC=C1 YNKMHABLMGIIFX-UHFFFAOYSA-N 0.000 description 1
- 229960002537 betamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 229960000725 brompheniramine Drugs 0.000 description 1
- ZDIGNSYAACHWNL-UHFFFAOYSA-N brompheniramine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Br)C=C1 ZDIGNSYAACHWNL-UHFFFAOYSA-N 0.000 description 1
- 229960004436 budesonide Drugs 0.000 description 1
- IFKLAQQSCNILHL-QHAWAJNXSA-N butorphanol Chemical compound N1([C@@H]2CC3=CC=C(C=C3[C@@]3([C@]2(CCCC3)O)CC1)O)CC1CCC1 IFKLAQQSCNILHL-QHAWAJNXSA-N 0.000 description 1
- 229960001113 butorphanol Drugs 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229960000428 carbinoxamine Drugs 0.000 description 1
- OJFSXZCBGQGRNV-UHFFFAOYSA-N carbinoxamine Chemical compound C=1C=CC=NC=1C(OCCN(C)C)C1=CC=C(Cl)C=C1 OJFSXZCBGQGRNV-UHFFFAOYSA-N 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000002939 cerumen Anatomy 0.000 description 1
- 229960001803 cetirizine Drugs 0.000 description 1
- YZIYKJHYYHPJIB-UUPCJSQJSA-N chlorhexidine gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.C1=CC(Cl)=CC=C1NC(=N)NC(=N)NCCCCCCNC(=N)NC(=N)NC1=CC=C(Cl)C=C1 YZIYKJHYYHPJIB-UUPCJSQJSA-N 0.000 description 1
- 229960003333 chlorhexidine gluconate Drugs 0.000 description 1
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 1
- YACLQRRMGMJLJV-UHFFFAOYSA-N chloroprene Chemical compound ClC(=C)C=C YACLQRRMGMJLJV-UHFFFAOYSA-N 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 229960005233 cineole Drugs 0.000 description 1
- 229940043350 citral Drugs 0.000 description 1
- WTEVQBCEXWBHNA-YFHOEESVSA-N citral B Natural products CC(C)=CCC\C(C)=C/C=O WTEVQBCEXWBHNA-YFHOEESVSA-N 0.000 description 1
- 229960002881 clemastine Drugs 0.000 description 1
- YNNUSGIPVFPVBX-NHCUHLMSSA-N clemastine Chemical compound CN1CCC[C@@H]1CCO[C@@](C)(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 YNNUSGIPVFPVBX-NHCUHLMSSA-N 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960000265 cromoglicic acid Drugs 0.000 description 1
- 229960001140 cyproheptadine Drugs 0.000 description 1
- JJCFRYNCJDLXIK-UHFFFAOYSA-N cyproheptadine Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2C=CC2=CC=CC=C21 JJCFRYNCJDLXIK-UHFFFAOYSA-N 0.000 description 1
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
- SOYKEARSMXGVTM-HNNXBMFYSA-N dexchlorpheniramine Chemical compound C1([C@H](CCN(C)C)C=2N=CC=CC=2)=CC=C(Cl)C=C1 SOYKEARSMXGVTM-HNNXBMFYSA-N 0.000 description 1
- 229960001882 dexchlorpheniramine Drugs 0.000 description 1
- 229960000520 diphenhydramine Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 description 1
- NLLGJEMIZSAJFN-AAFOHLTDSA-L disodium;(2r,3s,4r,5r)-2,3,4,5,6-pentahydroxy-1-[4-[4-[[(2r,3s,4r,5r)-2,3,4,5,6-pentahydroxy-1-sulfonatohexyl]amino]phenyl]sulfonylanilino]hexane-1-sulfonate Chemical compound [Na+].[Na+].C1=CC(NC([C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO)S([O-])(=O)=O)=CC=C1S(=O)(=O)C1=CC=C(NC([C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO)S([O-])(=O)=O)C=C1 NLLGJEMIZSAJFN-AAFOHLTDSA-L 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229960001971 ebastine Drugs 0.000 description 1
- MJJALKDDGIKVBE-UHFFFAOYSA-N ebastine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(=O)CCCN1CCC(OC(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 MJJALKDDGIKVBE-UHFFFAOYSA-N 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000005685 electric field effect Effects 0.000 description 1
- 238000007590 electrostatic spraying Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229960002179 ephedrine Drugs 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 229960005293 etodolac Drugs 0.000 description 1
- XFBVBWWRPKNWHW-UHFFFAOYSA-N etodolac Chemical compound C1COC(CC)(CC(O)=O)C2=N[C]3C(CC)=CC=CC3=C21 XFBVBWWRPKNWHW-UHFFFAOYSA-N 0.000 description 1
- 239000003172 expectorant agent Substances 0.000 description 1
- 210000003746 feather Anatomy 0.000 description 1
- 229960001419 fenoprofen Drugs 0.000 description 1
- 229960002390 flurbiprofen Drugs 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- 239000004088 foaming agent Substances 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229950009858 glucosulfone Drugs 0.000 description 1
- 210000002175 goblet cell Anatomy 0.000 description 1
- 239000000938 histamine H1 antagonist Substances 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229940071826 hydroxyethyl cellulose Drugs 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229960000930 hydroxyzine Drugs 0.000 description 1
- ZQDWXGKKHFNSQK-UHFFFAOYSA-N hydroxyzine Chemical compound C1CN(CCOCCO)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZQDWXGKKHFNSQK-UHFFFAOYSA-N 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 239000002563 ionic surfactant Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
- 229960000991 ketoprofen Drugs 0.000 description 1
- OZWKMVRBQXNZKK-UHFFFAOYSA-N ketorolac Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 OZWKMVRBQXNZKK-UHFFFAOYSA-N 0.000 description 1
- 229960004752 ketorolac Drugs 0.000 description 1
- 229960004958 ketotifen Drugs 0.000 description 1
- 229960003088 loratadine Drugs 0.000 description 1
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229960001474 meclozine Drugs 0.000 description 1
- 229960000582 mepyramine Drugs 0.000 description 1
- YECBIJXISLIIDS-UHFFFAOYSA-N mepyramine Chemical compound C1=CC(OC)=CC=C1CN(CCN(C)C)C1=CC=CC=N1 YECBIJXISLIIDS-UHFFFAOYSA-N 0.000 description 1
- 229960005042 mequitazine Drugs 0.000 description 1
- 229960004056 methdilazine Drugs 0.000 description 1
- HTMIBDQKFHUPSX-UHFFFAOYSA-N methdilazine Chemical compound C1N(C)CCC1CN1C2=CC=CC=C2SC2=CC=CC=C21 HTMIBDQKFHUPSX-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000004531 microgranule Substances 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 229940066491 mucolytics Drugs 0.000 description 1
- 229960005016 naphazoline Drugs 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-M naproxen(1-) Chemical compound C1=C([C@H](C)C([O-])=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-M 0.000 description 1
- 229960004398 nedocromil Drugs 0.000 description 1
- RQTOOFIXOKYGAN-UHFFFAOYSA-N nedocromil Chemical compound CCN1C(C(O)=O)=CC(=O)C2=C1C(CCC)=C1OC(C(O)=O)=CC(=O)C1=C2 RQTOOFIXOKYGAN-UHFFFAOYSA-N 0.000 description 1
- GYHFUZHODSMOHU-UHFFFAOYSA-N nonanal Chemical compound CCCCCCCCC=O GYHFUZHODSMOHU-UHFFFAOYSA-N 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- NUJGJRNETVAIRJ-UHFFFAOYSA-N octanal Chemical compound CCCCCCCC=O NUJGJRNETVAIRJ-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229960002698 oxatomide Drugs 0.000 description 1
- BAINIUMDFURPJM-UHFFFAOYSA-N oxatomide Chemical compound O=C1NC2=CC=CC=C2N1CCCN(CC1)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 BAINIUMDFURPJM-UHFFFAOYSA-N 0.000 description 1
- 229960005162 oxymetazoline hydrochloride Drugs 0.000 description 1
- BEEDODBODQVSIM-UHFFFAOYSA-N oxymetazoline hydrochloride Chemical compound Cl.CC1=CC(C(C)(C)C)=C(O)C(C)=C1CC1=NCCN1 BEEDODBODQVSIM-UHFFFAOYSA-N 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000008180 pharmaceutical surfactant Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003534 phenindamine Drugs 0.000 description 1
- 229950000688 phenothiazine Drugs 0.000 description 1
- 229960001802 phenylephrine Drugs 0.000 description 1
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 1
- 238000005554 pickling Methods 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 229960003910 promethazine Drugs 0.000 description 1
- KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 229950003786 rocastine Drugs 0.000 description 1
- 229920002631 room-temperature vulcanizate silicone Polymers 0.000 description 1
- 239000010670 sage oil Substances 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- VBSPHZOBAOWFCL-UHFFFAOYSA-N setastine Chemical compound C=1C=CC=CC=1C(C=1C=CC(Cl)=CC=1)(C)OCCN1CCCCCC1 VBSPHZOBAOWFCL-UHFFFAOYSA-N 0.000 description 1
- 229950003911 setastine Drugs 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000001433 sodium tartrate Substances 0.000 description 1
- 229960002167 sodium tartrate Drugs 0.000 description 1
- 235000011004 sodium tartrates Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229950004607 tazifylline Drugs 0.000 description 1
- 229950005829 temelastine Drugs 0.000 description 1
- 229960000351 terfenadine Drugs 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 229960001262 tramazoline Drugs 0.000 description 1
- QQJLHRRUATVHED-UHFFFAOYSA-N tramazoline Chemical compound N1CCN=C1NC1=CC=CC2=C1CCCC2 QQJLHRRUATVHED-UHFFFAOYSA-N 0.000 description 1
- 229960003223 tripelennamine Drugs 0.000 description 1
- 229960001128 triprolidine Drugs 0.000 description 1
- CBEQULMOCCWAQT-WOJGMQOQSA-N triprolidine Chemical compound C1=CC(C)=CC=C1C(\C=1N=CC=CC=1)=C/CN1CCCC1 CBEQULMOCCWAQT-WOJGMQOQSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229920001664 tyloxapol Polymers 0.000 description 1
- 229960004224 tyloxapol Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000004073 vulcanization Methods 0.000 description 1
Images
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B11/00—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use
- B05B11/0005—Components or details
- B05B11/0062—Outlet valves actuated by the pressure of the fluid to be sprayed
- B05B11/0072—A valve member forming part of an outlet opening
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/02—Inhalators with activated or ionised fluids, e.g. electrohydrodynamic [EHD] or electrostatic devices; Ozone-inhalators with radioactive tagged particles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/08—Inhaling devices inserted into the nose
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B5/00—Electrostatic spraying apparatus; Spraying apparatus with means for charging the spray electrically; Apparatus for spraying liquids or other fluent materials by other electric means
- B05B5/16—Arrangements for supplying liquids or other fluent material
- B05B5/1691—Apparatus to be carried on or by a person or with a container fixed to the discharge device
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B11/00—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use
- B05B11/0005—Components or details
- B05B11/0062—Outlet valves actuated by the pressure of the fluid to be sprayed
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B11/00—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use
- B05B11/01—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use characterised by the means producing the flow
- B05B11/10—Pump arrangements for transferring the contents from the container to a pump chamber by a sucking effect and forcing the contents out through the dispensing nozzle
- B05B11/1001—Piston pumps
- B05B11/1009—Piston pumps actuated by a lever
- B05B11/1011—Piston pumps actuated by a lever without substantial movement of the nozzle in the direction of the pressure stroke
Abstract
一种可对人体腔提供喷雾的喷雾装置(4),它包括一喷雾发生器,一流体盛器和一具有输出表面的鼻甲(5),尤其是一种能产生含流体直线部分和从直线部分的一端散开的喷雾锥形部分的喷雾的装置。该装置最好是静电喷雾装置,喷雾锥形部分含有充电小滴。还涉及一种将流体从喷雾装置喷射到鼻腔中而装置基本上不伸到鼻孔中的方法。本发明的装置和方法在装置基本上不伸到鼻孔中的情况下将鼻治疗剂温和而可靠地送到鼻腔中,尤其是需要减轻充血的鼻腔中。
Description
发明技术领域
本发明涉及一种喷雾装置,具体是一种能产生喷雾的装置,这种喷雾包括一流体直线部分(ligament)和从直线部分的一端扩散的喷雾锥形部分。本发明尤其涉及一种不需要插到鼻孔中就能将柔和的喷雾送到鼻腔的弹性喷雾装置。本发明还涉及一种喷雾装置基本上不伸进鼻孔中就将流体从喷雾装置喷射到鼻腔中的方法。更具体地说,本发明还涉及一种静电喷雾一种液体的方法,即液体最初以直线部分的形式从喷雾头射出,这部分加入鼻孔,此后在库仑力的影响下分裂成小滴,以形成雾状的喷雾。
发明的技术背景
诸如花粉热或由于着凉引起的充血之类的影响鼻子部位的疾病治疗通常采用鼻内喷雾装置。现在人们发现,鼻腔的粘膜可用作瞄准身体其它部位的药物的方便的输送站。例如,见国际专利申请第WO 92/11049号,它公开了一种笔形装置,以便实施胰岛素的鼻内给药。但是,将流体喷射到鼻内的装置总是做成该装置必须部分插入要治疗的鼻孔中。使用这种装置不仅对使用者有潜在的不卫生和/或不方便,而且往往还要求使用者的头往后仰,以防喷射时流体流出鼻子。
鼻腔是身体中用药物的困难部位。为了进入鼻腔内,必须通过鼻孔将药物导入鼻子前庭,再送到鼻腔的后面,然后通过鼻瓣窄的裂口。药物一旦经过鼻瓣,就要求分布在下方和中间鼻甲骨的血管组织上。鼻甲骨是上覆纤毛上皮和酒杯细胞(goblet cell)的可竖立组织的指状凸起。当鼻子充血时,鼻甲骨扩张和隔离气道。为了治疗,诸如解充血药、消炎药或抗组胺药的表面药必须敷在鼻甲骨的上皮上,这样才有药理作用。鼻甲骨是鼻子高度有血管的部位,因此是吸收系统药的最佳部位。
现在已经发现,使喷雾具有一特定的直线部分长度和从直线部分的一端扩散的适当大小的喷雾圆锥部分,喷雾可瞄准鼻子的适当部位,尤其是鼻甲骨,以吸收有效喷雾,而不需要将装置插入鼻孔中。
用一静电装置作为产生喷雾的较佳装置。WO96/40441描述了一将流体送到鼻子或口中的静电装置。EP-A-501,725也描述了直线模式的静电喷雾装置。共同申请的还未授权的申请PCT/GB97/02746描述了适用于静电喷射低电阻系数流体诸如水液的装置。
前述的WO96/40441在第9页第19-21行描述了该装置的使用是将鼻甲插入鼻孔并进行喷雾,而使用者同时吸气。因此,这就要忍受与已有技术装置同样的限制,即在治疗中需要将装置插入鼻孔中。这就会引起不方便,并感到不卫生,从而禁止使用这种装置。但是,从鼻孔外面喷射,往往使喷雾输送到指定目标、尤其是鼻子的鼻甲骨的效率低,那是因为大部分流体喷射在指定目标的外面,使流体不舒服地流掉。
现在发现一种能克服这些问题的喷雾装置。
因此,本发明的一个目的是提供一种喷雾装置,它能提高将流体送到鼻腔中的有效性和/或舒适性。
本发明的另一个目的是提供一种喷雾装置,该装置在基本上不伸进鼻孔的情况下就能将流体送到鼻中。
本发明的另一个目的是提供一种喷雾装置,它能输送柔和平缓的喷雾,使使用者感到舒适。
本发明的另一个目的是提供一种喷雾装置,它能有效输送小单位容积的流体。
本发明的再一个目的是提供一种鼻子喷雾装置,它能输送一种流体,但在鼻前庭或鼻孔中不会有湿润的感觉。
发明简要说明
按照本发明,提供一种静电喷雾装置,该装置包括一喷雾发生器,一流体盛器和一鼻甲,该鼻甲具有一外端和穿过其中的通道,其中:
i)流体盛器含有一种配制的可接收的流体,该流体包括一种从药物、香料、盐、表面活性剂及其混合物中选择而配制的可接收治疗剂;以及
ii)该装置可产生一种具有穿过鼻甲中的通道延伸的流体直线部分的喷雾,一施加到流体中的高压使直线部分散开成喷雾锥形部分,该直线部分具有一在直线部分、垂直于该直线部分的平面和鼻甲的外端的相交处的鼻甲端部和一发送端,其中喷雾锥形部分从直线部分的发送端扩散;
直线部分具有从0.5至8ms-1的速度,直线部分的从鼻甲端部到发送端的长度在1至20毫米之间,由此该装置可以喷雾至使用者的鼻孔内,以对准鼻甲骨。
发明的详细介绍
流体
本发明的喷雾装置优选地包括含药学上可接受液体的液体贮器,液体包括选自药物、调味剂、盐、表面活性剂及其混合物的药学上可接受的治疗剂。液体任选地包括溶解于其中或分散于其中的其它辅剂。液体可为含水的或不含水的。合适的含水液体包括水,以及水和水可混溶的溶剂,如甘油、丙二醇或诸如乙醇或异丙醇的醇类的混合物。也可使用油包水型或水包油型的含水乳剂。优选的液体是含水溶液、分散液或水包油型乳剂。合适的不含水的液体包括聚乙二醇、甘油、丙二醇、二甲基异山梨醇、硅油、酮类、醚类和它们的混合物。
虽然对电阻率的范围没有限定,但本发明特别应用于低电阻率的液体,特别是体积电阻率低于1×108ohm.cm,优选的电阻率低于1×104ohm.cm,更优选的是低于1×103ohm.cm。需要时,液体可包含电阻率修饰剂,如药学上可接受的盐,以使体积电阻率处于所需的范围里。
液体优选的是药学上可接受的鼻内用载体。优选的是,鼻用组合物是等渗的,即它与血液和泪液的渗透压相同。本发明组合物所需的等渗性可使用已经存在的氯化钠,或其它药学上可接受的试剂,如右旋糖、硼酸、柠檬酸、酒石酸钠、柠檬酸钠、磷酸钠、磷酸钾、丙二醇或其它无机或有机溶质来达到。氯化钠对于含钠离子的缓冲液尤为优选。Remington′s PharmaceuticalSciences(Alfonso Gennaro第18版,1990)1491-1497页揭示了氯化钠等价物的例子,在此并入供参考。
药物
液体可包括各种药物。“药物”表示对机体有治疗作用的药物或其它物质。药物的合适水平是0.001-20%,优选的是0.01-5%,更优选的是0.1-5%。应当明白,特定药物的水平根据包括药物的效力、安全曲线、溶解度/分散的容易性和迅速的作用等许多因素而定。药物可为,在使用时对施加部位有作用的物质,如减充血剂、抗组胺或抗炎药物,或供全身吸收的药物,如抗病毒药、抗抑郁药、抗呕吐药、解热药或激素或类似的药物。药物可溶于液体或不溶于液体,或是分散在液体里的细分散颗粒液体或固体。
合适的减充血剂包括去甲唑啉、曲马唑啉、赛洛唑啉、萘甲唑林、tetrahydrazoline、假麻黄碱、麻黄碱、苯福林,它们的药学上可接受的盐,如盐酸盐,和它们的混合物。优选的减充血剂选自去甲唑啉、赛洛唑啉,它们的药学上可接受的盐,和它们的混合物。本发明使用的特别优选的是盐酸去甲唑啉,它溶于水。当用于本发明组合物时,去充血剂优选的存在浓度为约0.01%-3.0%,更优选的是约0.01-1%。
用于本发明的抗组胺包括,但不限于,速效的组胺H-1受体拮抗剂。这类H-1受体抗组胺药选自下列抗组胺类:烷基烷、乙醇胺、亚乙基二胺、哌嗪、吩噻嗪、哌啶。有用的速效抗组胺例子包括阿伐斯汀、卡比沙明、苯海拉明、氯苯那敏、溴苯那敏、右氯苯那敏、多西那敏、氯马斯汀、异丙嗪、阿利马嗪、甲地嗪、羟嗪、美吡拉敏、曲吡那敏、美克洛嗪、曲普利啶、阿扎他定、赛庚啶、rocastine、苯茚胺或其药学上可接受的盐,和它们的混合物。其它有用的抗组胺类包括特非那定、氮 斯汀、西替利嗪、阿司咪唑、依巴斯汀、酮替芬、洛草氨酸、氯雷他定、左旋卡巴斯汀、美喹他嗪、奥沙米特、司他斯汀、他齐茶碱、替美斯汀或其药学上可接受的盐,和它们的混合物。当用于本发明组合成份时,抗组胺组分优选的浓度为约0.01-3.0%,更优选的是约0.01-1%。
也可使用抗炎药物,如皮质类固醇。该类中特别优选的是糖皮质激素,选自倍他米松、9-去氟肤轻松、氟替米松、memetasone、布地奈德,其药学上可接受的盐,和它们的混合物。用于本发明组合成份时,抗炎药优选的浓度为约0.001%-0.1%,更优选的是约0.01%-0.1%。
在此还有用的是黄嘌呤衍生物,如咖啡因和甲基黄嘌呤等;抗变态反应药;溶粘蛋白剂;抗胆碱药;非鸦片类止痛剂,如扑热息痛、乙酰水杨酸、布洛芬、依托度酸、fenbuprofen、非诺洛芬、酮咯酸、氟比洛芬、吲哚美辛、酮洛芬、萘普生,其药学上可接受的盐,和它们的混合物;诸如布托啡诺的鸦片类止痛剂;白三烯受体拮抗剂;肥大细胞(mast cell)稳定剂,如色甘酸钠、奈多罗米和洛草氨酸;和脂肪氧合酶抑制化合物。
在WO97/46243、EP-A-780127、US-A-5,656,255和US-A-5,705,490中可发现合适药物的其它例子。
调味剂
各种调味和/或芳香组分(如,醛和酯)可用于本发明的液体。这些包括,如甲醇、樟脑、桉脑、苯甲醛(樱桃、杏仁);柠檬醛(柠檬、酸橙);橙花醛;癸醛(橙、柠檬);C-8醛、C-9醛和C-12醛(柑橘类水果);甲苯醛(樱桃、杏仁);2,6-二甲基辛醛(绿色水果);2-十二碳烯醛(柑橘、中国柑桔);和草本植物组分,如麝草香、迷迭香和鼠尾草油。适用于本发明的另外的芳香组分包括美国专利4,136,163(授予Watson等)、美国专利4,459,425(授予Amano等)和美国专利4,230,688(授予Rowsell等)中所揭示的芳香组分,所有这些专利文献并入本文供参考。也可使用这些芳香物的混合物。
表面活性剂
液体也可包含一种或多种药学上可接受的表面活性剂。这类表面活性剂可用于分散或乳化药物或调味剂,以增加穿越鼻膜的吸收,或凭本身的性能作为治疗剂,如供软化耳垢。表面活性剂可为阴离子、非离子、阳离子或两性离子型的,优选的是非离子型的。用于本发明的典型的非离子表面活性剂包括:山梨醇酸酐的脂肪酸偏酯的聚氧乙烯衍生物,如吐温80;脂肪酸的聚氧乙烯衍生物,如聚氧乙烯50硬脂酸酯,以及氧乙烯化的叔辛基苯酚甲醛聚合物(Sterling Organics出售,商品名Tyloxapol)或它们的混合物。通常的浓度为0.1-3重量%。
盐
液体也可包含一种或多种药学上可接受的盐。该盐可为无机盐,如氯化钠,或有机盐,如柠檬酸钠。
其它辅剂
液体可进一步包含其它组分,如增稠剂、湿润剂、悬浮助剂、形成胶囊助剂、螯合剂和保存剂。
用药学上可接受的增稠剂使组合物的粘度保持在选定的水平。合适的增稠剂包括,如黄蓍胶、甲基纤维素、微晶纤维素、羧甲基纤维素、脱乙酰壳多糖、羟丙基纤维素、羟丙基甲基纤维素、羟甲基纤维素、羟乙基纤维素、羧基乙烯基聚合物、carbomer等或其药学上可接受的盐。也可使用这类增稠剂的混合物。增稠剂优选的浓度取决于所选的试剂。重要的是使用能达到选定粘度的用量。通常通过加入这类粘稠剂而从溶液中制备粘稠的组合物。
用于本发明的液体也可包含约0.01%-5%湿润剂,以抑制粘膜干燥,并防止刺激。也可使用各种药学上可接受的湿润剂,包括,如山梨醇、丙二醇、聚乙二醇、甘油或它们的混合物。增稠剂的粘度可随选定的试剂而变,但这些试剂的存在与否,或它们的浓度不是本发明的必要特征。
通常使用药学上可接受的保存剂以增加本发明组合物的贮存期限。可使用各种保存剂,包括,如苄基醇、对羟苯甲酸酯类、苯乙基醇、硫柳汞、氯丁醇、葡萄糖洗必太或氯苄烷铵。用于本发明的最优选的保存剂系统是氯苄烷铵、葡萄糖酸洗必太和作为螯合剂的EDTA二钠的组合。虽然根据所选定的试剂有所改变,但保存剂合适的浓度,基于总总量,为0.001%-2%。
喷雾装置和喷雾性能
喷雾装置通常包括一控制喷射流体剂量的设备。它可能是如一双位开关那样简单,允许使用者根据需要控制剂量。该喷雾装置能提供一个单位流体剂量,更具体地说,一单位剂量具有从约1至约100μl、较佳的是从约1至约20μl、更佳的是从约5至约15μl的容量。尤其是在较佳实施例中,该装置能提供上述容量的多单位剂量。该剂量的容量较佳的是预先设定,但也可由使用者按照所需的容量进行调节。该装置较适当的是包括一储存流体的盛器,及有选择地从盒子里输送一单位剂量给喷雾发生器的给药设备。该给药设备例如可是一计量阀或一注射泵。
该装置能产生具有流体直线部分的喷雾,该直线部分从鼻甲处延伸,并具有一鼻甲端部和一发送端,该喷雾还包括一喷雾锥形部分,它自直线部分的发送端散开。所谓的“鼻甲端部”是一点,在该点处画一垂直于直线部分的轴线的平面(下面叫做“鼻甲平面”),该平面正好与鼻甲的外部接触,且与直线部分的中心相交。该直线部分从鼻甲端部到发送端较佳的是具有从约1至约20mm、更佳的是从约1至约10mm、最佳的是从约2至约8mm、特别是从约3至约6mm的长度。
在较佳的实施例里,喷雾锥形部分具有从约10至约90°、较佳的是从约20至约50°、更佳的是从约30至约40°的锥形角。在静电装置里,直线部分的长度和喷雾锥形角可通过以下方式进行调节,即改变流体的粘性或表面张力,改变流体流速或输出速率,或通过施加电压、电位梯度或使用强化电场电极改变电场强度。
直线部分的总长度可大于、较佳的是大于从鼻甲端部至发送端的长度,因为直线部分较佳的是从在鼻甲平面的装置一侧的一点处、诸如从这里所述的弹性的自密封阀处发生、并通过在该鼻甲里的一通道。从直线部分的发生点至鼻甲平面的距离在从约2至约15mm、较佳的是在从约3至约10mm、更佳的是在从约5至约9mm的范围内。这样,鼻甲可作为强化电场,从而有助于控制直线部分的长度。为此,鼻甲较佳的是非导电材料、诸如聚丙烯之类的塑料,但较佳的是柔软的热塑性弹性体,当抵着鼻子时它能提供较大的舒适性。这里所述的用于自密封阀的弹性体也适用于鼻甲。
国际专利申请第WO 96/40441号、欧洲专利第EP-A-501,725号和待批申请第PCT/GB97/02746号介绍了能以直线方式喷雾的静电装置。本装置较佳的是一种按照欧洲专利第EP-A-501,725号或待PCT/GB97/02746号中的实施例的装置,其中,通过机械设备产生喷射,而提供给流体的高电压将使喷射或直线部分散开成喷雾锥形部分。该喷射可由例如一注射泵进行。适当的喷射速率从约0.5至约0.8、较佳的是从约1至约3ms-1。
适当的高电压在从约1kV至约10kV、较佳的是从约2kV至约7kV、更佳的是从约2kV至约5kV的范围内。该电压可较容易地由一低电压(1.5V就足够了)电池加上一升压变压器提供给流体,即使是在小型手持式装置里。该电池较佳的是耐用型的,并且可重复充电。如果使用金属注射泵,电压可施加在通过该泵的流体上,而该泵较佳的是由绝缘的塑料壳体包裹。此外,该流体也可由插入流体的电极充电。发生器可由使用者通过外部开关启动,而该开关还可以使泵起动。该开关较佳的是包括一金属部分,使用者可利用该金属部分实现至高电压线路的地回路。PCT/GB97/02746介绍了一种整个装置结构的适当布局。这样,使用者不会得到净电荷。也可使用交流设备来提供交流电压,从而防止产生电荷积聚。
启动该装置将产生喷雾。喷雾的直线部分在散开形成喷雾锥形部分前延伸通过鼻孔开口,进入前庭,较佳的是鼻瓣(nasal valve)开口的一短距离内。该装置可制成能同时喷射两支喷雾,以便直接进入两个鼻孔。两支喷雾可由两个单独的给药设备产生,也可通过使用一‘Y’型阀将一单独的喷射分成两部分来提供。
为了在低单位容量时提供完全的停止—启动,该装置较佳的包括—弹性的自密封输出阀,该阀具有一流体侧和一输送侧,当对流体侧的流体施加压力时,该阀打开以允许流体通过,当压力消失时,阀关闭。这里所述的“输出阀”是指该弹性阀是最后一个分配阀,该装置没有其它的元件来机械地约束或改变在该阀的下游侧的流体流动。在较佳的实施例里,该阀是一狭缝阀。该阀可包括一条狭缝或两条以上的相交的狭缝,以便形成例如交叉的形状。然而,较佳的是,该阀包括一条狭缝。虽然该阀可以是扁平的,但较佳的是一圆拱形的,这意味着它是一个具有凹槽的非扁平的阀,诸如具有半球形的或截头圆锥形的圆拱。在较佳的实施例里,该阀基本上是半球形的圆拱,具有沿着其周边的凸缘,这样,可用一套环将该阀固定在该装置上。阀的直径(包括凸缘)一般从约2至6mm,而圆拱部分具有从约1至约4mm、通常约2.5mm的直径,并具有从内向外约0.5至约1.5mm、较佳的是约1mm的厚度。该阀不需要均匀的厚度。在较佳的实施例里,该阀的圆拱形的外表面是半球形的,但内表面在圆拱形顶部处、即形成狭缝的地方可略平坦。适当的狭缝宽度从约50至约400μm、较佳的是从约150至约250μm。应该明白,狭缝的宽度涉及狭缝第一次形成时的最长尺寸。这里所使用的术语“弹性体”涉及一种材料,它既可弹性压缩,又可弹性伸长。可使用的弹性体的范围包括(但不限于)聚氨酯、氯丁二烯、丁基合成橡胶、丁二烯和苯乙烯-丁二烯橡胶,以及硅弹性体,诸如2份室温硫化(RTV)硅树脂。这里较佳的是使用2份硅树脂RTVs。适当的硅树脂RTVs的商标是Nusil,它具有从约30至约80的肖氏A硬度、较佳的是从约40至70肖氏A硬度。该弹性体可有选择地与适当的可塑剂或发泡剂混合,以使它们具有更好的压缩性。该弹性体也可有其它的分布在其中的材料,以便改变它的性能,诸如它的导电性。如果使用低撕裂强度的弹性体,在狭缝保持打开一较长时间时狭缝的宽度可能会增加。该狭缝阀可通过使用一具有尖锐末端的针刺穿一注塑成形的、具有与所需阀相同尺寸和形状的弹性密封件而形成。狭缝的宽度大致与针的宽度成比例。该针可以是一扁平的刀片,也可以具有多边形或圆形的横截面。该针较佳的是具有多边形、特别是圆形的横截面。已经发现,尖锐边缘的针产生的切口使用时更象是一条扁平缝,而不是一个孔。这可能导致喷射不是笔直的、或者甚至产生两个以上的喷射,从而可能导致不可靠的和不可预知的喷射。针的适当直径从约100至约350、较佳的是从150至250μm。当使用硅树脂弹性体时,较佳的是刺穿针在形成狭缝后迅速退出,以避免狭缝不必要地扩大。还发现,弹性密封件的几何形状和刺穿的方法对狭缝形成的效率和重复性具有显著的影响。如果密封件的刺穿是从圆拱的内侧而不是从外侧进行,可更可靠地形成狭缝。
当在流体侧对流体施加压力时,阀打开,当压力消失时,阀关闭。如前面所述的,可由诸如注射泵之类的定量设备对流体施加压力。所施加的压力适合于在从约200至约5000mbar(20至500kPa)的范围内,较佳的是从约500至约3000mbar(50至300kPa)的范围内。通过阀的流动速率一般与所施加的压力成比例,适合于从约5至约50、较佳的是从约5至约30μls-1的范围内。在该压力下,并具有所述的阀类型及狭缝尺寸时,可获得输出速率在从约0.5至约8、较佳的是从约1至约3ms-1范围内的笔直的流体直线部分。
所喷出的直线部分的直径部分地是由流动速率决定的,且一般小于狭缝阀的宽度。按照所述的流动速率,即使在阀的狭缝宽度是200μm,也可获得小于50μm的直线部分直径。直线部分的直径显著地影响喷雾在散开成锥形部分后的喷雾的微粒大小,微粒尺寸大部分类似于直线部分的直径。这里所述的直线方式的静电喷雾的特点是,可获得紧密分布的、几乎单一散开的喷雾。这样,有可能获得从约20至约80的、较佳的是从约30至约70、更佳的是从约40至约60μm的中间小滴尺寸,微粒尺寸分布通常具有小于5、一般小于2μm、较佳的是小于1μm的标准偏差。一般的共识是,对于鼻内喷雾来说,10μm或更小的微粒尺寸是理想的,这样,微粒不会被携带入肺里。然而,应该相信,喷雾微粒所具有的静电荷将使它们不大可能被携带至鼻子后面,因为带电微粒趋向于相当快地发现接地表面。
末端阀的完全停止动作可通过导入阀工作后期的压力释放特征得到进一步的改善。这将采用在流体盛器上形成旁路的方式,以便使由于弹性体的松弛而加压的任何剩余的流体返回到一盛器里,而不是从阀出口处滴落。
如果需要,可一前一后地使用几个自密封阀,以便获得较高容量的喷射量,同时仍较佳地维持较小的喷雾微粒尺寸。用来制成阀的密封件可通过传统的注塑模制工艺方便地制造出来。
方法
这里所述的喷雾装置适合于向体腔、特别是人的鼻子、嘴巴或耳朵喷雾。低容量和温和的喷雾也使它适合于例如眼药喷雾。较佳的是,该装置是一鼻内喷雾装置。实施从喷雾装置向鼻腔提供流体的较佳方法包括,将流体喷入鼻腔,而基本上不需要该装置进入鼻孔。这里所谓的“基本上不需要进入鼻孔”是指,没有一个喷嘴或类似东西插入鼻子前庭。使用时,该装置的鼻甲较佳的是与鼻孔开口接触,从而获得这里所述的、与鼻甲有关的强化电场效果的全部好处。如果由使用者提供压力,为确保接触或有助于其取向,可使鼻孔略微张开或与隔膜软骨重叠,但不管怎样,鼻甲将不会完全被鼻孔包围。
现在仅作为例子并参考附图来介绍本发明,其中:
图1是人的鼻子的剖视图;
图2是按照本发明的喷雾装置的立体图;
图3是图2中的喷雾装置的简化的剖视图,它显示了鼻甲上的弹性喷嘴与定量给药装置的关系;
图4是一示意的零件剖视图,它显示了由本发明的装置实施的喷雾;
图5是本发明的弹性输出阀的放大的剖视图。
参看图1,鼻子包括鼻腔1,鼻甲骨2位于其中,盘旋的指状结构上覆盖着上皮,而鼻腔容易发炎。鼻腔通过两个鼻孔3通向外面。由于鼻甲骨位于鼻腔的较后部位上,因此如不将喷雾装置插入鼻孔里将难以对它们进行有效的喷雾。
参看图2和3,它们显示了喷雾装置4具有柔软的弹性鼻甲5,它将紧抵使用者的鼻孔开口而不插入鼻孔里。该鼻甲上设有一与喷雾泵7连接的通道6(其内部细节未画出),该喷雾泵被用来产生通过弹性输出阀8的带状雾。该装置的绝缘壳体9还包容(未画出)可更换的流体盛器、电池、变压器和电路,以便由变压器提供高压给流体。该装置还设置一启动机构10,它通过机械启动泵,并使其释放以输出预定单位剂量的流体。该启动机构包括金属部分,以便提供自使用者至高压线路的接地回路。
下面参看图4,喷雾包括直线部分11和具有锥形角θ的锥形部分12。具体地说,锥形角可通过从一固定距离喷射至显象纸、然后测量喷射图案的直径来测得,或直接使用带背照射的高速视频照相术观察喷雾。直线部分具有发送端13和鼻甲端部14,直线部分在发送端13分裂成锥形部分,而鼻甲端部14由平面A-A与直线部分11的相交点限定。平面A-A垂直于直线部分的轴线,且正好与鼻甲5的末端接触。
图5显示了按照本发明的一弹性输出阀8。该圆形对称的喷嘴包括一将喷嘴固定在喷雾装置上的凸缘15、一圆拱形头部16、一凹槽17和一狭缝18,狭缝18从凹槽延伸至圆拱形头部的顶部。该喷嘴是通过在基本相同形状的模具里注塑形成的,然后,用尖锐的、具有圆形横截面和200μm直径的针从凹槽的内侧向外刺破圆拱形头部。
例子
下面的例子进一步介绍和论证了在本发明范围内的实施例。这些例子只是为了举例说明,而并不是用来限定本发明的范围。
例子1
本发明的流体是通过合成下列成分准备的,它利用了类似于下面所述的、传统的混合技术。
组分 重量%
盐酸羟甲唑啉 0.31
柠檬酸钠二水合物 1.75
柠檬酸 0.35
四丁酚醛 0.70
二葡萄糖酸洗必太 0.054
氯苄烷铵 0.02
樟脑 0.04
桉树脑 0.02
EDTA二钠二水合物 0.01
蒸馏水 加到100毫升
在一适当大小的容器里加入上述成分,每次用水混和,以便在加入后一成分前让其溶解。在所有的成分加入后,使用纯净水使该批料达到适当重量。该溶液具有120ohm.cm的体电阻系数。将该溶液注入一柔软的薄片盒里并安装在图2所示的静电喷雾装置里。该装置的鼻甲对着鼻孔,这样方向的装置喷雾的直线部分将进入鼻孔。启动该装置,在约1秒的时间里喷射约8μl的溶液。这样喷射的流体可减轻鼻充血,且不会在鼻子上或内侧产生显而易见的湿润。这种低剂量和温和的输送使使用者不会觉察到来自喷雾装置的任何可感觉到的机械冲击。
例子2
通过合成下列成分准备另一种流体,它利用了类似于例子1所述的、传统的混合技术。
组分 重量%
9-去氟肤轻松 0.025
氯苯那敏 0.350
左旋卡巴斯汀 0.0125
丙二醇 2.000
聚乙二醇 1.000
亚乙基二胺四乙酸 0.050
氯苄烷铵 0.010
蒸馏水 加到100毫升
用例子1的方式进行鼻内喷雾,使用大约10μl的流体混合物,以减轻过敏症或类似过敏的症状。
例子3
通过合成下列成分准备本发明的一种流体,它利用了类似于例子1所述的、传统的混合技术。
组分 重量%
二丙酸氯地米松单水合物 0.042
氯苯那敏 0.500
Avicel RC-5911 0.200
右旋糖 5.100
吐温80 0.050
氯苄烷铵 0.020
苯乙基醇 0.025
蒸馏水 加到100毫升
1微晶纤维素和羧甲基纤维素,由FMC公司提供。
用例子1的方式进行鼻内喷雾,使用大约10μl的流体混合物,以便减轻过敏症或类似过敏的症状。
Claims (6)
1.一种静电喷雾装置(4),该装置包括一喷雾发生器,一流体盛器和一鼻甲(5),该鼻甲具有一外端和穿过其中的通道(6),其中:
i)流体盛器含有一种配制的可接收的流体,该流体包括一种从药物、香料、盐、表面活性剂及其混合物中选择而配制的可接收治疗剂;以及
ii)该装置可产生一种具有穿过鼻甲(5)中的通道(6)延伸的流体直线部分(11)的喷雾,一施加到流体中的高压使直线部分散开成喷雾锥形部分(12),该直线部分具有一在直线部分、垂直于该直线部分的平面和鼻甲的外端的相交处的鼻甲端部(14)和一发送端(13),其中喷雾锥形部分从直线部分的发送端(13)扩散;其特征在于,
直线部分具有从0.5至8ms-1的速度,直线部分的从鼻甲端部(14)到发送端(13)的长度在1至20毫米之间,由此该装置可以喷雾至使用者的鼻孔(3)内,以对准鼻甲骨(2)。
2.如权利要求1所述的静电喷雾装置,其特征在于,将范围从1kV至10kV的电压施加到流体上。
3.如权利要求1或2所述的静电喷雾装置,其特征在于,喷雾圆锥部分有一从10至90°的锥角。
4.如权利要求1所述的静电喷雾装置,其特征在于,该装置能提供一容量从1至20的单位流体剂量。
5.如权利要求4所述的静电喷雾装置,其特征在于,该装置能提供多单位流体剂量。
6.如权利要求1所述的静电喷雾装置,其特征在于,所述流体盛器是可替换的。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB9806939.6A GB9806939D0 (en) | 1998-03-31 | 1998-03-31 | A spray device |
GB9806939.6 | 1998-03-31 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1295489A CN1295489A (zh) | 2001-05-16 |
CN1196506C true CN1196506C (zh) | 2005-04-13 |
Family
ID=10829643
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB998046493A Expired - Fee Related CN1196506C (zh) | 1998-03-31 | 1999-03-22 | 带有改进的喷雾几何形状的鼻子喷雾装置 |
Country Status (18)
Country | Link |
---|---|
EP (1) | EP1082157B1 (zh) |
JP (1) | JP2002509773A (zh) |
KR (1) | KR100375196B1 (zh) |
CN (1) | CN1196506C (zh) |
AT (1) | ATE255442T1 (zh) |
AU (1) | AU749158B2 (zh) |
BR (1) | BR9909294A (zh) |
CA (1) | CA2324952A1 (zh) |
CZ (1) | CZ20003512A3 (zh) |
DE (1) | DE69913341T2 (zh) |
EG (1) | EG22631A (zh) |
GB (1) | GB9806939D0 (zh) |
HU (1) | HUP0101365A3 (zh) |
ID (1) | ID26793A (zh) |
NO (1) | NO20004902L (zh) |
PE (1) | PE20000607A1 (zh) |
TR (1) | TR200002806T2 (zh) |
WO (1) | WO1999049923A1 (zh) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001074431A2 (en) * | 2000-04-03 | 2001-10-11 | Battelle Memorial Institute | Dispensing devices and liquid formulations |
CA2414118C (en) * | 2000-07-06 | 2007-04-10 | Bespak Plc | Dispensing apparatus |
GB2364320B (en) * | 2000-07-06 | 2002-06-12 | Bespak Plc | Dispensing apparatus |
GB2367756B (en) | 2000-10-12 | 2003-01-08 | Bespak Plc | Dispensing apparatus |
ZA200306564B (en) * | 2001-02-26 | 2004-10-15 | Optinose As | Nasal devices. |
BR0208303A (pt) | 2001-03-22 | 2004-03-09 | Battelle Memorial Institute | Formações liquidas para pulverização eletroidrodin mica contendo polìmero e partìculas suspensas |
GB2375098B (en) | 2001-04-30 | 2003-08-27 | Bespak Plc | Improvements in valves for pressurised dispensing containers |
GB2384190A (en) | 2002-01-22 | 2003-07-23 | Bespak Plc | Dispensing device for a powdered product |
GB0602980D0 (en) * | 2006-02-14 | 2006-03-29 | Optinose As | Delivery device and method |
GB2448193A (en) * | 2007-04-05 | 2008-10-08 | Optinose As | Nasal delivery device |
JP2013070768A (ja) * | 2011-09-27 | 2013-04-22 | Panasonic Corp | 機能性微粒子放出装置 |
JP2013070767A (ja) * | 2011-09-27 | 2013-04-22 | Panasonic Corp | 機能性微粒子放出装置 |
US11554229B2 (en) | 2013-03-26 | 2023-01-17 | OptiNose Inc. | Nasal administration |
CN107280954A (zh) * | 2016-04-12 | 2017-10-24 | 上海合微智能科技有限公司 | 智能控制的盐疗洗鼻器 |
EP4028085A4 (en) * | 2019-09-13 | 2023-10-04 | Janssen Pharmaceuticals, Inc. | INTRANASAL ADMINISTRATION OF ESKETAMINE |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US1599111A (en) * | 1925-06-05 | 1926-09-07 | Eugene E Beadle | Inhaler |
FR1146256A (fr) * | 1956-03-23 | 1957-11-08 | Perfectionnements apportés aux objets du genre des inhalateurs de poche | |
EP0501725B1 (en) * | 1991-03-01 | 2001-06-13 | The Procter & Gamble Company | Spraying of liquids |
GB2273673A (en) * | 1992-12-22 | 1994-06-29 | Unilever Plc | Dental active delivery system |
GB9511514D0 (en) * | 1995-06-07 | 1995-08-02 | Ici Plc | Electrostatic spraying |
-
1998
- 1998-03-31 GB GBGB9806939.6A patent/GB9806939D0/en not_active Ceased
-
1999
- 1999-03-22 CZ CZ20003512A patent/CZ20003512A3/cs unknown
- 1999-03-22 DE DE69913341T patent/DE69913341T2/de not_active Expired - Fee Related
- 1999-03-22 CA CA002324952A patent/CA2324952A1/en not_active Abandoned
- 1999-03-22 WO PCT/IB1999/000469 patent/WO1999049923A1/en not_active Application Discontinuation
- 1999-03-22 AT AT99942605T patent/ATE255442T1/de not_active IP Right Cessation
- 1999-03-22 HU HU0101365A patent/HUP0101365A3/hu unknown
- 1999-03-22 BR BR9909294-8A patent/BR9909294A/pt not_active Application Discontinuation
- 1999-03-22 CN CNB998046493A patent/CN1196506C/zh not_active Expired - Fee Related
- 1999-03-22 ID IDW20001936A patent/ID26793A/id unknown
- 1999-03-22 EP EP99942605A patent/EP1082157B1/en not_active Expired - Lifetime
- 1999-03-22 JP JP2000540884A patent/JP2002509773A/ja not_active Abandoned
- 1999-03-22 AU AU32696/99A patent/AU749158B2/en not_active Ceased
- 1999-03-22 TR TR2000/02806T patent/TR200002806T2/xx unknown
- 1999-03-22 KR KR10-2000-7010817A patent/KR100375196B1/ko not_active IP Right Cessation
- 1999-03-30 PE PE1999000253A patent/PE20000607A1/es not_active Application Discontinuation
- 1999-03-31 EG EG32499A patent/EG22631A/xx active
-
2000
- 2000-09-29 NO NO20004902A patent/NO20004902L/no not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
JP2002509773A (ja) | 2002-04-02 |
AU3269699A (en) | 1999-10-18 |
AU749158B2 (en) | 2002-06-20 |
DE69913341D1 (de) | 2004-01-15 |
KR100375196B1 (ko) | 2003-03-07 |
PE20000607A1 (es) | 2000-09-22 |
CZ20003512A3 (cs) | 2001-08-15 |
WO1999049923A1 (en) | 1999-10-07 |
HUP0101365A2 (hu) | 2001-08-28 |
GB9806939D0 (en) | 1998-05-27 |
CN1295489A (zh) | 2001-05-16 |
EP1082157A1 (en) | 2001-03-14 |
BR9909294A (pt) | 2000-12-05 |
EG22631A (en) | 2003-05-31 |
HUP0101365A3 (en) | 2001-12-28 |
DE69913341T2 (de) | 2004-10-07 |
KR20010052226A (ko) | 2001-06-25 |
CA2324952A1 (en) | 1999-10-07 |
NO20004902D0 (no) | 2000-09-29 |
ATE255442T1 (de) | 2003-12-15 |
EP1082157B1 (en) | 2003-12-03 |
TR200002806T2 (tr) | 2001-01-22 |
NO20004902L (no) | 2000-11-29 |
ID26793A (id) | 2001-02-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6471095B1 (en) | Dosing and delivering system | |
CN1196506C (zh) | 带有改进的喷雾几何形状的鼻子喷雾装置 | |
CN1134308C (zh) | 静电喷雾装置 | |
CN1104262C (zh) | 用于粉碎液体的装置和提供液珠的方法 | |
AU748289B2 (en) | Dosing and delivering system | |
US6503481B1 (en) | Compositions for aerosolization and inhalation | |
US5655517A (en) | Dispensing device | |
EP0224352B1 (en) | Ocular treatment | |
CN1334746A (zh) | 鼻吸器 | |
JPS62197071A (ja) | 液滴の霧状物を得るための装置および吸入器 | |
CN1076987C (zh) | 静电喷射装置和方法 | |
MXPA00009620A (en) | Nasal spray device with elastomeric valve | |
MXPA01007126A (en) | Dosing and delivering system | |
JP2000093483A (ja) | 洗浄用スパウト装置 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C19 | Lapse of patent right due to non-payment of the annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |