CN1748695A - 治疗鼻息肉和鼻息肉病的阿苯达唑鼻腔凝胶剂 - Google Patents
治疗鼻息肉和鼻息肉病的阿苯达唑鼻腔凝胶剂 Download PDFInfo
- Publication number
- CN1748695A CN1748695A CN 200410078469 CN200410078469A CN1748695A CN 1748695 A CN1748695 A CN 1748695A CN 200410078469 CN200410078469 CN 200410078469 CN 200410078469 A CN200410078469 A CN 200410078469A CN 1748695 A CN1748695 A CN 1748695A
- Authority
- CN
- China
- Prior art keywords
- nasal
- polyp
- albendazole
- treatment
- jelly
- 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.)
- Pending
Links
- 208000000592 Nasal Polyps Diseases 0.000 title claims abstract description 54
- 208000016366 nasal cavity polyp Diseases 0.000 title claims abstract description 52
- HXHWSAZORRCQMX-UHFFFAOYSA-N albendazole Chemical compound CCCSC1=CC=C2NC(NC(=O)OC)=NC2=C1 HXHWSAZORRCQMX-UHFFFAOYSA-N 0.000 title claims abstract description 46
- 229960002669 albendazole Drugs 0.000 title claims abstract description 46
- 229940100652 nasal gel Drugs 0.000 title claims 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 10
- 238000011282 treatment Methods 0.000 claims abstract description 41
- 239000004615 ingredient Substances 0.000 claims description 3
- 238000002647 laser therapy Methods 0.000 claims 1
- 238000011477 surgical intervention Methods 0.000 claims 1
- 235000015110 jellies Nutrition 0.000 abstract description 19
- 239000008274 jelly Substances 0.000 abstract description 18
- 208000037062 Polyps Diseases 0.000 abstract description 16
- 238000002360 preparation method Methods 0.000 abstract description 3
- 238000013532 laser treatment Methods 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 20
- 239000007921 spray Substances 0.000 description 16
- 239000007922 nasal spray Substances 0.000 description 12
- 210000001331 nose Anatomy 0.000 description 11
- 239000007923 nasal drop Substances 0.000 description 10
- 210000003928 nasal cavity Anatomy 0.000 description 9
- 206010028748 Nasal obstruction Diseases 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 239000003862 glucocorticoid Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- KUVIULQEHSCUHY-XYWKZLDCSA-N Beclometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O KUVIULQEHSCUHY-XYWKZLDCSA-N 0.000 description 6
- 208000006673 asthma Diseases 0.000 description 6
- 229960004495 beclometasone Drugs 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 206010061218 Inflammation Diseases 0.000 description 5
- 241000158526 Nasalis Species 0.000 description 5
- 230000004054 inflammatory process Effects 0.000 description 5
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 4
- 201000007100 Pharyngitis Diseases 0.000 description 4
- 206010044302 Tracheitis Diseases 0.000 description 4
- 229960001138 acetylsalicylic acid Drugs 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 4
- 230000002421 anti-septic effect Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 230000003203 everyday effect Effects 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 206010039083 rhinitis Diseases 0.000 description 4
- 150000003431 steroids Chemical class 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- 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 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 206010030113 Oedema Diseases 0.000 description 3
- 208000026935 allergic disease Diseases 0.000 description 3
- 230000007815 allergy Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 206010006451 bronchitis Diseases 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- WMWTYOKRWGGJOA-CENSZEJFSA-N fluticasone propionate 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](C)[C@@](C(=O)SCF)(OC(=O)CC)[C@@]2(C)C[C@@H]1O WMWTYOKRWGGJOA-CENSZEJFSA-N 0.000 description 3
- 210000003630 histaminocyte Anatomy 0.000 description 3
- 210000004969 inflammatory cell Anatomy 0.000 description 3
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 3
- 206010025482 malaise Diseases 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 229940098458 powder spray Drugs 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 210000001364 upper extremity Anatomy 0.000 description 3
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
- 229920003091 Methocel™ Polymers 0.000 description 2
- VXTGHWHFYNYFFV-UHFFFAOYSA-N albendazole S-oxide Chemical compound CCCS(=O)C1=CC=C2NC(NC(=O)OC)=NC2=C1 VXTGHWHFYNYFFV-UHFFFAOYSA-N 0.000 description 2
- 229950010075 albendazole sulfoxide Drugs 0.000 description 2
- 229960004436 budesonide Drugs 0.000 description 2
- 239000003246 corticosteroid Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000002651 drug therapy Methods 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 229960000289 fluticasone propionate Drugs 0.000 description 2
- 210000004907 gland Anatomy 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 229940071826 hydroxyethyl cellulose Drugs 0.000 description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229960003943 hypromellose Drugs 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 230000000749 insecticidal effect Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 210000002850 nasal mucosa Anatomy 0.000 description 2
- 229940097496 nasal spray Drugs 0.000 description 2
- 231100000957 no side effect Toxicity 0.000 description 2
- 210000003695 paranasal sinus Anatomy 0.000 description 2
- 230000035807 sensation Effects 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 description 2
- 210000001944 turbinate Anatomy 0.000 description 2
- OXFSTTJBVAAALW-UHFFFAOYSA-N 1,3-dihydroimidazole-2-thione Chemical class SC1=NC=CN1 OXFSTTJBVAAALW-UHFFFAOYSA-N 0.000 description 1
- KTPMVZCGIJJWCD-UHFFFAOYSA-N 1-hydroxypyridin-2-imine Chemical compound ON1C=CC=CC1=N KTPMVZCGIJJWCD-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- VOBDXTSTTMAKHK-VHDCPBDGSA-N 3870-07-3 Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)COC(=O)C)[C@@]1(C)C[C@@H]2O VOBDXTSTTMAKHK-VHDCPBDGSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 206010009137 Chronic sinusitis Diseases 0.000 description 1
- 208000025678 Ciliary Motility disease Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 206010014950 Eosinophilia Diseases 0.000 description 1
- 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 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 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 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000003892 Kartagener syndrome Diseases 0.000 description 1
- HLFSDGLLUJUHTE-SNVBAGLBSA-N Levamisole Chemical compound C1([C@H]2CN3CCSC3=N2)=CC=CC=C1 HLFSDGLLUJUHTE-SNVBAGLBSA-N 0.000 description 1
- 241001629511 Litchi Species 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
- 235000011613 Pinus brutia Nutrition 0.000 description 1
- 241000018646 Pinus brutia Species 0.000 description 1
- 101100545004 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) YSP2 gene Proteins 0.000 description 1
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000000507 anthelmentic effect Effects 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 229940098032 beconase Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000005098 blood-cerebrospinal fluid barrier Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 239000006013 carbendazim Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 208000027157 chronic rhinosinusitis Diseases 0.000 description 1
- 210000004081 cilia Anatomy 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 208000016097 disease of metabolism Diseases 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000013129 endoscopic sinus surgery Methods 0.000 description 1
- 238000002674 endoscopic surgery Methods 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 229940033835 flonase Drugs 0.000 description 1
- 229960000676 flunisolide Drugs 0.000 description 1
- XSFJVAJPIHIPKU-XWCQMRHXSA-N flunisolide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O XSFJVAJPIHIPKU-XWCQMRHXSA-N 0.000 description 1
- 229960000785 fluocinonide Drugs 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 230000002962 histologic effect Effects 0.000 description 1
- 230000037189 immune system physiology Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000000608 laser ablation Methods 0.000 description 1
- VNYSSYRCGWBHLG-AMOLWHMGSA-N leukotriene B4 Chemical compound CCCCC\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC(O)=O VNYSSYRCGWBHLG-AMOLWHMGSA-N 0.000 description 1
- GWNVDXQDILPJIG-NXOLIXFESA-N leukotriene C4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O GWNVDXQDILPJIG-NXOLIXFESA-N 0.000 description 1
- 229960001614 levamisole Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229940002297 nasacort Drugs 0.000 description 1
- 208000020877 nasal cavity benign neoplasm Diseases 0.000 description 1
- 201000010762 nasal cavity neoplasm Diseases 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000007119 pathological manifestation Effects 0.000 description 1
- 208000011906 peptic ulcer disease Diseases 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 201000009266 primary ciliary dyskinesia Diseases 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- MIXMJCQRHVAJIO-TZHJZOAOSA-N qk4dys664x Chemical compound O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O MIXMJCQRHVAJIO-TZHJZOAOSA-N 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229940072265 rhinocort Drugs 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229960002117 triamcinolone acetonide Drugs 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明涉及使用阿苯达唑制备鼻腔凝胶剂，并用阿苯达唑的鼻腔凝胶剂治疗鼻息肉和鼻息肉病，还用于在手术治疗、激光治疗等手段治疗鼻息肉后防止鼻息肉复发。
Description
本发明涉及治疗鼻腔息肉的阿苯达唑滴鼻剂、阿苯达唑鼻腔喷雾剂和阿苯达唑鼻腔气雾剂以及它们的应用。
鼻息肉是一种常见病，成年人的发病率在1％-2％左右。根据临床观察，有内源性支气管哮喘的病人鼻息肉的发病率为30％，有阿司匹林不耐受(支气管型)的病人息肉发病率高达50％。鼻息肉的病因迄今不明，计有感染、变态反应、创伤、化学刺激、代谢性疾病、精神因素等学说。
鼻息肉的治疗比较困难，手术治疗易复发，复发率高达15％-20％。其药物治疗通常采用各种类固醇药物，但采用类固醇药物后，会引起对类固醇药物的依赖性。这些原因使得鼻息肉的研究与治疗日益受到重视，发现新的治疗鼻息肉的药物，使之有效，同时不产生依赖性，成为人们关注的焦点。
一、鼻息肉的发病原因：
从组织病理学来说，鼻息肉是鼻腔或鼻窦内灰白色、阻塞性块状组织，含有水肿的液体，起源于鼻腔的完整表层上皮，多为两侧和多发性。组织学分类80％-90％为嗜酸细胞性息肉，是以嗜酸细胞增多为特征的炎性细胞浸润，其它的炎性细胞有肥大细胞、巨嗜细胞、浆细胞和淋巴细胞等。合并支气管哮喘和阿司匹林敏感的鼻息肉属于嗜酸细胞性。在合并纤维囊性变、Kartagener’s综合症(纤毛运动障碍)以及上颌窦后鼻孔息肉是以嗜中性粒细胞增多为特征。
根据临床与病理表现分析，变态反应可能是鼻息肉的病因。鼻息肉的形成是由于多种原因或未知原因的刺激导致鼻粘膜表层损伤、上皮脱落，使成纤维细胞增殖并分泌细胞因子，促进肥大细胞分化和生长，肥大细胞在非特异性因素刺激下发生脱颗粒反映，引起炎性介质的释放和嗜酸细胞浸润，组织胺、LTC4、LTB4等介质增多，造成渗出和水肿；嗜酸细胞释放的MBP、ECP等破坏鼻粘膜血管的神经，使血管通透性增加，进一步加重了炎症反应。由于持续的炎症反应，形成息肉。
另一方面，由于鼻腔粘膜炎性细胞浸润、水肿，压力增加，造成上皮破裂，固有层从缺损处突出，周围的粘膜延续生长，脱出的组织表层上皮细胞化生，形成息肉蒂部，血管长入，并建立血管蒂，腺体被拉长，长入息肉中，形长管状腺体，在炎性反应和重力的作用下，息肉不断增大。
二、鼻息肉的治疗现状：
鼻息肉的现代治疗主张采用糖皮质激素与手术治疗相结合的方法。
(一)手术治疗原则
对于小的单发息肉摘除较为简单，对于多发的和复发的息肉应采用较广泛的手术，目前采用的功能性鼻内窥镜手术(FES)较为测定，可将每个暴露的筛房清除干净。对于多次复发的息肉，主张进行广泛的筛窦和部分蝶窦切除术。也可选择性地采用YAG激光切除鼻息肉，出血少，病人痛苦轻，但不适用与严重的顽固性鼻息肉患者。
对伴有支气管哮喘和阿司匹林敏感的患者也主张行彻底的鼻息肉切除术，手术不仅不会引起和加重哮喘，而且由于手术清除了鼻腔和鼻窦的病灶，恢复了正常的鼻通气功能而使哮喘病情明显好转。但是合并哮喘的病人手术后复发率较高，而且手术不能改变病人对阿司匹林的敏感性和气道的高反应性，因此手术后应进行糖皮质激素治疗。
(二)糖皮质激素治疗
近年来，大量的资料证明糖皮质激素在鼻息肉的治疗中有显著的疗效。因为鼻息肉是鼻腔的持续性炎症性疾病，任何彻底的手术均不能将鼻息肉的病因清除，只有采用糖皮质激素和手术联合治疗，才能延缓和防止息肉的复发。
目前采取的治疗原则是，对于初发的较小的息肉，单纯采用鼻内喷入糖皮质激素治疗，便可使息肉缩小或消失；对于较大的息肉，可加用口服、肌注或下鼻甲粘膜下注射等全身用药，采用鼻内局部喷药作维持治疗，可使部分病人免除手术治疗；对严重的病例，应在接受糖皮质激素治疗后手术，并于手术后坚持一年以上的鼻局部吸入治疗，虽然不能完全阻止复发，但可在较长时间内避免复发。常用的鼻喷剂有丙酸倍氯米松(BDP，beclomethason dipropionate，商品名Beconase)、丁地去炎松(budesonide，商品名Rhinocort)、丙酸氟替卡松(fluticasone propionate，商品名Flonase)、丙炎松(triamcinolone acetonide，商品名Nasacort)、9-去氟肤轻松(flunisolide，商品名Rhinalar)、醋酸曲安缩松等，局部用药不影响鼻腔纤毛系统的功能，但都需要长期用药，虽然有报道即使观察至5年也无副作用发；但也有很多文献报道，持续局部使用糖皮质激素可引起咽部真菌感染。对于有类固醇使用禁总症者，如骨质疏松、消化性溃疡、严重高血压、糖尿病、精神科疾病、癫痫、青光眼、白内障等，不能使用皮质类固醇治疗鼻息肉。
也有报道采用塞替派(thiotepa)于手术后辅助治疗鼻息肉的报道。塞替派是抗肿瘤药，参与机体的免疫反应，抑制免疫过程的诱导期及增殖期，抑制细胞增殖及变态反应，有减轻充血、阻止再生的作用(新药与临床，1996；15(5)：318)。
三、阿苯达唑简介
阿苯达唑，英文通用名称为Albendazole；一般名称为：阿苯哒唑、阿丙条、5-丙硫-2-苯并咪唑氨甲酸甲酯、丙硫达唑、丙巯咪唑、丙硫咪唑等。为广谱驱虫药。可影响虫体多种生化代谢途径。本药可以抑制肠道寄生虫对葡萄糖的摄取，导致虫体内的糖原耗竭；也可与虫体微管蛋白结合抑制微管聚集，从而抑制分泌颗粒转运和其它亚细胞器运动；还可抑制虫体线粒体延胡索酸还原酶系统，减少ATP生成，从而干扰虫体生存和繁殖而导致其死亡。本药为高效广谱驱虫药，系苯并咪唑类药物中杀虫作用最强的一种。口服吸收缓慢。口服后2.5-3小时血药浓度达峰值，一日15mg/kg分两次或分三次口服所达到的曲线下面积(AUC)相同。本药生物利用度小于5％，在体内分布于肝、肾、肌肉且可透过血-脑脊液屏障，故脑组织内也有一定浓度。本药在肝脏内转化为丙硫苯咪唑-亚砜与丙硫苯咪唑-砜，前者为杀虫成分。原药与砜衍生物在血中的浓度极低，不能测出，而丙硫苯咪唑-亚砜的浓度变化很大，自0.04μg/mL至0.55μg/mL不等，平均0.16μg/mL。原药及其代谢产物在24小时内有87％随尿排泄，肾脏清除率为0.16-0.81L/h，13％经消化道排泄。半衰期为8.5-10.5小时。药物在体内无积蓄作用。不被血液透析清除。。
四、迄今，国内外都尚未见任何将阿苯达唑鼻腔凝胶剂用于治疗鼻息肉或防止鼻息肉复发的报道或文献记载。
本发明将阿苯达唑作为单独的有效成分或与其它药物一起配成复方，制成鼻腔给药的剂型，这些剂型包括，但不限于：滴鼻剂、喷雾剂、气雾剂和粉雾剂。
本发明所述的用阿苯达唑或用含阿苯达唑的复方制成的滴鼻剂、喷雾剂、气雾剂和粉雾剂的适应症，包括，但不限于以下病症：鼻息肉和鼻息肉病、慢性鼻窦炎、鼻息肉或鼻息肉病、鼻炎、咽炎、气管炎和支气管炎。
使用本发明所述的用阿苯达唑或用含阿苯达唑的复方制成的滴鼻剂、喷雾剂、气雾剂和粉雾剂，对于鼻息肉或鼻息肉病患者，直接鼻腔给药，可有效地使大的鼻息肉缩小，使小的鼻息肉消失；或于鼻息肉切除术后给药，可阻止鼻息肉的复发；对于鼻炎、咽炎、气管炎和支气管炎，可以缓解炎症症状。
本发明所述的滴鼻剂、喷雾剂和气雾剂，均符合《中华人民共和国药典》(2000年版二部)关于滴鼻剂、喷雾剂和气雾剂的定义。
本发明所述的鼻息肉，是本领域的技术人员所熟知的，现代的医学书籍中有其准确的定义，指鼻腔内的灰白色、荔枝状新生物。其病理学改变如前所述。本发明所述的鼻炎、咽炎、气管炎和支气管炎，也是本领域的技术技术人员所熟知的，现代的医学书籍中有其准确的定义。
通过以下实施例对本发明的阿苯达唑鼻腔凝胶剂的制备、用其治疗鼻息肉或鼻息肉病的应用进行描述。需说明的是，下述实施例只是用来说明而非限制本发明，本领域技术人员所熟知的通过其他给药途径将左旋咪唑用于治疗鼻息肉或鼻息肉病、鼻炎、咽炎、气管炎和支气管炎的技术均在本发明的范围内。
实施例1采用卡泊普制备阿苯达唑鼻腔凝胶剂
称取卡泊普940(Carbopol940)2g；取100ml 80℃左右的无菌蒸馏水；边搅拌边向热水中加入卡泊普，全部加入卡泊普后，持续搅拌12h。待温度降低后，加入100mg阿苯达唑，再加入适量防腐剂，再搅拌30min后，及得阿苯达唑凝胶，分装到鼻腔喷雾剂瓶中或滴鼻剂瓶中，即得阿苯达唑鼻腔凝胶剂。
实施例2采用羟甲基纤维素制备阿苯达唑鼻腔凝胶剂
称取羟甲基纤维素2g；取100ml 80℃左右的无菌蒸馏水；边搅拌边向热水中加入卡泊普，全部加入卡泊普后，持续搅拌12h。待温度降低后，加入100mg阿苯达唑，再加入适量防腐剂，再搅拌30min后，及得阿苯达唑凝胶，分装到鼻腔喷雾剂瓶中或滴鼻剂瓶中，即得阿苯达唑鼻腔凝胶剂。
实施例3采用羟乙基纤维素制备阿苯达唑鼻腔凝胶剂
称取羟乙基纤维素2g；取100ml 80℃左右的无菌蒸馏水；边搅拌边向热水中加入卡泊普，全部加入卡泊普后，持续搅拌12h。待温度降低后，加入100mg阿苯达唑，再加入适量防腐剂，再搅拌30min后，及得阿苯达唑凝胶，分装到鼻腔喷雾剂瓶中或滴鼻剂瓶中，即得阿苯达唑鼻腔凝胶剂。
实施例4采用羟丙甲纤维素制备阿苯达唑鼻腔凝胶剂
称取羟丙甲纤维素2g；取100ml 80℃左右的无菌蒸馏水；边搅拌边向热水中加入卡泊普，全部加入卡泊普后，持续搅拌12h。待温度降低后，加入100mg阿苯达唑，再加入适量防腐剂，再搅拌30min后，及得阿苯达唑凝胶，分装到鼻腔喷雾剂瓶中或滴鼻剂瓶中，即得阿苯达唑鼻腔凝胶剂。
实施例5使用阿苯达唑鼻腔凝胶剂治疗鼻息肉
(1)病例和方法：
鼻息肉大小的判断：参照Johansen等的方法[Johansen LV，et al.Clin Otolaryngol，1993；18：524]，经前鼻镜观察，以鼻甲为参照物记分。鼻息肉未超过中鼻甲缘者记0.5分，超过中鼻甲缘未达下鼻甲上缘者记1分，超过下鼻甲上缘未达下缘者记2分，达到下缘者记3分。减少1.5分为显效，1分为有效。
鼻塞程度按轻、中、重度3分法记录，减少2分为显效，1分为有效。
12例鼻息肉患者中男8例，女4例。平均年龄33岁(25～41岁)。鼻息肉达3分者3例，2分者6例，1分者3例。重度鼻塞4例，中度鼻塞6例，轻度鼻塞2例。
将患者随机分为治疗组(6例)和对照组(6例)，治疗组含鼻息肉3分者2例，2分者3例，1分者1例，重度鼻塞2例，中度鼻塞3例，轻度鼻塞1例；对照组含鼻息肉3分者1例，2分者3例，1分者2例，重度鼻塞2例，中度鼻塞3例，轻度鼻塞1例。对照组采用丙酸倍氯米松喷雾剂治疗，每天鼻腔给药喷三次，持续两周后，第三周改为每天喷二次，第四周改为每天喷一次，疗程为一个月；治疗组采用阿苯达唑鼻腔凝胶剂治疗，每天喷鼻腔给药喷一次，持续用药一个月。
丙酸倍氯米松喷雾剂中，丙酸倍氯米松的剂量为50ug/0.14ml每喷；阿苯达唑鼻腔凝胶剂中，阿苯达唑的剂量为100ug/0.1ml每喷。
于用药两周和用药一个月后复查，观察鼻息肉大小、记分变化、鼻塞减轻程度以及有无副作用发生等。
(2)结果：
鼻息肉大小记分的改变：对照组在治疗一月后，鼻息肉均见明显回缩，其中3分者治疗结束后鼻息肉已越过鼻内孔，1分者有1例鼻息肉消失。治疗组鼻息肉也都明显回缩，3分者2例在治疗结束时均回缩至下鼻甲上缘，2分者有1例、1分者有2例鼻息肉消失。
鼻塞症状的改善：治疗组和对照组中患者的鼻塞症状均有不同程度的改善。治疗组的2例重度鼻塞中，有1例用药1个月后嗅觉有所恢复；对照组的2例重度鼻塞中有1例用药1个月后嗅觉有所恢复。治疗组中度鼻塞改善不明显者1例，对照组中度鼻塞改善不明显者2例。
结论：对于鼻息肉的药物治疗，国外多采用皮质类固醇的鼻腔喷雾或气雾治疗。采用阿苯达唑鼻腔凝胶剂，其疗效与丙酸倍氯米松喷雾剂相似或稍好于丙酸倍氯米松喷雾剂。
实施例6阿苯达唑鼻腔凝胶剂治疗鼻息肉复发
一位55岁女性，确诊多发性鼻息肉，鼻内窥镜手术切除息肉，术后40天，鼻息肉复发，再次摘除复发的息肉。再过40天后复查，鼻息肉又复发。此时改用阿苯达唑鼻腔凝胶剂行鼻局部给药治疗，每天一次，持续一月，复发的鼻息肉变小。继续一月后复查，鼻息肉消失。
Claims (3)
1.将阿苯达唑作为有效成分或有效成分之一制成的鼻腔凝胶剂。
2.阿苯达唑在用于治疗鼻息肉和鼻息肉病的鼻腔凝胶剂的生产中的应用。
3.阿苯达唑在鼻息肉手术治疗、激光治疗等外科治疗后防止鼻息肉复发的鼻腔凝胶剂的生产中的应用。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410078469 CN1748695A (zh) | 2004-09-14 | 2004-09-14 | 治疗鼻息肉和鼻息肉病的阿苯达唑鼻腔凝胶剂 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410078469 CN1748695A (zh) | 2004-09-14 | 2004-09-14 | 治疗鼻息肉和鼻息肉病的阿苯达唑鼻腔凝胶剂 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1748695A true CN1748695A (zh) | 2006-03-22 |
Family
ID=36604474
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410078469 Pending CN1748695A (zh) | 2004-09-14 | 2004-09-14 | 治疗鼻息肉和鼻息肉病的阿苯达唑鼻腔凝胶剂 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1748695A (zh) |
-
2004
- 2004-09-14 CN CN 200410078469 patent/CN1748695A/zh active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2156840B1 (en) | Use of mometasone furoate for treating airway passage and lung diseases | |
| JP6837486B2 (ja) | 加齢に関連する認知障害及び神経炎症を予防及び／又は治療する方法 | |
| US20200101067A1 (en) | Use of levocetirizine and montelukast in the treatment of anaphylaxis | |
| AU2010239515A1 (en) | Compositions and methods for treating burns | |
| ES2389539T3 (es) | Métodos y composiciones para el tratamiento del asma | |
| JP2008255089A (ja) | 上皮改善剤 | |
| US20040180868A1 (en) | Composition and method for treating inflammations by reducing C-reactive protein | |
| Craig et al. | Efficacy and safety of azelastine nasal spray for the treatment of allergic rhinitis | |
| US20120165299A1 (en) | Combination medicament | |
| Schenkel | Features of mometasone furoate nasal spray and its utility in the management of allergic rhinitis | |
| CN1236765C (zh) | 治疗鼻息肉和鼻息肉病的左旋咪唑新剂型 | |
| CN100446766C (zh) | 治疗鼻息肉和鼻息肉病的阿苯达唑新剂型 | |
| CN1748695A (zh) | 治疗鼻息肉和鼻息肉病的阿苯达唑鼻腔凝胶剂 | |
| CN1748685A (zh) | 治疗鼻息肉和鼻息肉病的奥苯达唑鼻腔凝胶剂 | |
| US20110224160A1 (en) | Use of Escin for Treatment of Type IV Hypersensitivity Reaction | |
| CN1748680A (zh) | 治疗鼻息肉和鼻息肉病的甲苯咪唑新剂型 | |
| CN1748690A (zh) | 治疗鼻息肉和鼻息肉病的奥苯达唑新剂型 | |
| Davies et al. | Drug treatment for nasal allergy. | |
| CN1751684A (zh) | 治疗鼻息肉和鼻息肉病的阿司咪唑新剂型 | |
| US20040029893A1 (en) | Method of treatment of non-invasive mucositis | |
| CN100496492C (zh) | 治疗慢性鼻窦炎的甲苯咪唑新剂型 | |
| CN114007690B (zh) | 治疗哮喘的方法 | |
| WO2007100079A1 (ja) | 三環性トリアゾロベンゾアゼピン誘導体を含有する、アレルギー性眼疾患またはアレルギー性鼻疾患の予防または治療剤 | |
| US11382925B2 (en) | Agent for treating retinal disease | |
| WO2020180279A1 (ru) | Фармацевтическая композиция для интраназального введения |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20070309 Address after: No. 12, Huayuan Road, Jiangsu, Nanjing Applicant after: Jiangsu Simcere Pharmaceutical Research Company Limited Address before: 5C, building six, 6 District, far road, century garden, Beijing, Haidian District Applicant before: Wang Heyao Co-applicant before: Zheng Wenjie |
|
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |