JP2001252354A - Dosing device - Google Patents
Dosing deviceInfo
- Publication number
- JP2001252354A JP2001252354A JP2000070089A JP2000070089A JP2001252354A JP 2001252354 A JP2001252354 A JP 2001252354A JP 2000070089 A JP2000070089 A JP 2000070089A JP 2000070089 A JP2000070089 A JP 2000070089A JP 2001252354 A JP2001252354 A JP 2001252354A
- Authority
- JP
- Japan
- Prior art keywords
- drug
- administration device
- line
- heart
- gene therapy
- 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
- 239000003814 drug Substances 0.000 claims abstract description 206
- 229940079593 drug Drugs 0.000 claims abstract description 199
- 210000002216 heart Anatomy 0.000 claims abstract description 54
- 238000002347 injection Methods 0.000 claims abstract description 37
- 239000007924 injection Substances 0.000 claims abstract description 37
- 238000001415 gene therapy Methods 0.000 claims description 91
- 238000001647 drug administration Methods 0.000 claims description 87
- 230000004087 circulation Effects 0.000 claims description 43
- 238000000034 method Methods 0.000 claims description 26
- 230000000694 effects Effects 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 230000003293 cardioprotective effect Effects 0.000 claims description 2
- 239000000243 solution Substances 0.000 abstract description 30
- 238000011282 treatment Methods 0.000 abstract description 16
- 210000004165 myocardium Anatomy 0.000 abstract description 3
- 230000002068 genetic effect Effects 0.000 abstract 2
- 230000001012 protector Effects 0.000 abstract 1
- 230000002107 myocardial effect Effects 0.000 description 53
- 239000003223 protective agent Substances 0.000 description 52
- 238000011144 upstream manufacturing Methods 0.000 description 23
- 239000002502 liposome Substances 0.000 description 20
- 208000019622 heart disease Diseases 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 11
- 239000008280 blood Substances 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 10
- 239000003507 refrigerant Substances 0.000 description 9
- 210000000709 aorta Anatomy 0.000 description 8
- 239000000372 cardioplegic agent Substances 0.000 description 8
- 239000012659 cardioprotective agent Substances 0.000 description 8
- 229940045200 cardioprotective agent Drugs 0.000 description 8
- 210000002064 heart cell Anatomy 0.000 description 8
- 230000002612 cardiopulmonary effect Effects 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 210000005240 left ventricle Anatomy 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 230000037452 priming Effects 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- 238000002054 transplantation Methods 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 230000036770 blood supply Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 210000001105 femoral artery Anatomy 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 210000001147 pulmonary artery Anatomy 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 206010056370 Congestive cardiomyopathy Diseases 0.000 description 2
- 201000010046 Dilated cardiomyopathy Diseases 0.000 description 2
- 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 2
- 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 2
- 230000000747 cardiac effect Effects 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000002826 coolant Substances 0.000 description 2
- 210000004351 coronary vessel Anatomy 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- 238000007599 discharging Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 229960001031 glucose Drugs 0.000 description 2
- 206010020871 hypertrophic cardiomyopathy Diseases 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
- 210000004072 lung Anatomy 0.000 description 2
- 208000031225 myocardial ischemia Diseases 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- 101150096316 5 gene Proteins 0.000 description 1
- 101150111660 53 gene Proteins 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 101100116283 Arabidopsis thaliana DD11 gene Proteins 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 208000020446 Cardiac disease Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010020710 Hyperphagia Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 208000009525 Myocarditis Diseases 0.000 description 1
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
- 239000000006 Nitroglycerin Substances 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical compound [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000004004 anti-anginal agent Substances 0.000 description 1
- 230000001315 anti-hyperlipaemic effect Effects 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 230000008321 arterial blood flow Effects 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- BPKIGYQJPYCAOW-FFJTTWKXSA-I calcium;potassium;disodium;(2s)-2-hydroxypropanoate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].C[C@H](O)C([O-])=O BPKIGYQJPYCAOW-FFJTTWKXSA-I 0.000 description 1
- 239000008148 cardioplegic solution Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000007887 coronary angioplasty Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940124567 diuretic antihypertensive agent Drugs 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 206010014665 endocarditis Diseases 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 229960003883 furosemide Drugs 0.000 description 1
- 229960003711 glyceryl trinitrate Drugs 0.000 description 1
- 210000003709 heart valve Anatomy 0.000 description 1
- 208000018578 heart valve disease Diseases 0.000 description 1
- 210000001308 heart ventricle Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229940124975 inotropic drug Drugs 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003601 intercostal effect Effects 0.000 description 1
- 210000002977 intracellular fluid Anatomy 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 235000020830 overeating Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 210000003516 pericardium Anatomy 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 229960001404 quinidine Drugs 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 210000005245 right atrium Anatomy 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000009210 therapy by ultrasound Methods 0.000 description 1
- 210000000779 thoracic wall Anatomy 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- LMJSLTNSBFUCMU-UHFFFAOYSA-N trichlormethiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC(C(Cl)Cl)NS2(=O)=O LMJSLTNSBFUCMU-UHFFFAOYSA-N 0.000 description 1
- 229960004813 trichlormethiazide Drugs 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000008320 venous blood flow Effects 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
- 229960005080 warfarin Drugs 0.000 description 1
Landscapes
- Infusion, Injection, And Reservoir Apparatuses (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、薬物投与装置に関
するものである。TECHNICAL FIELD The present invention relates to a drug administration device.
【０００２】[0002]
【従来の技術】近年、我が国では心臓病が増加してお
り、心臓病が日本人の死亡原因の第２位を占めるまでに
なった。その中でも特に、我が国では、動脈硬化に起因
した虚血性心疾患が増加している。これは、西欧化した
食生活や食べ過ぎによって、高脂血症や糖尿病が増えた
ことが原因と考えられる。2. Description of the Related Art In recent years, heart disease has increased in Japan, and heart disease has become the second leading cause of death in Japanese. Above all, in Japan, ischemic heart disease caused by arteriosclerosis is increasing. This is considered to be due to an increase in hyperlipidemia and diabetes due to the westernized diet and overeating.
【０００３】また、虚血性心疾患の他にも、心臓病とし
ては、何らかの原因で刺激伝導系に異常が起こり、不整
脈、心臓の弁膜の開閉に支障をきたす心臓弁膜症、心室
がしだいに拡張し収縮力が低下してくる拡張型心筋症、
心筋の一部が肥大してくる肥大型心筋症、心筋梗塞、狭
心症、心筋炎、心内膜炎、心外膜炎などが知られてい
る。心臓は、血液を全身に送りだすという生命にとって
根本的で重要な役割を有しているため、これらいずれの
病気を発病した場合でも、患者にとっては致命的なもの
となる。[0003] In addition to ischemic heart disease, as heart disease, abnormalities occur in the stimulus conduction system for some reason, arrhythmia, valvular heart disease which interferes with opening and closing of the heart valve, and ventricle expansion gradually. Dilated cardiomyopathy with reduced contractility
Hypertrophic cardiomyopathy, myocardial infarction, angina pectoris, myocarditis, endocarditis, epicarditis, and the like, in which a portion of the heart muscle is enlarged, are known. The heart plays a fundamental and important role in life, sending blood throughout the body, so that any of these diseases becomes fatal to patients.
【０００４】このような心臓疾患の治療法としては、抗
狭心症薬（ニトログリセリン）、血液凝固阻止薬（ワー
ファリン）、強心剤（ジキタリス製剤）、血小板粘着抑
制薬、抗不整脈薬（キニジン）、利尿降圧薬（トリクロ
ルメチアジド、フロセミド）、抗高脂血症薬などを患者
に投与する薬物療法が、知られている。[0004] Treatments for such heart diseases include antianginal drugs (nitroglycerin), anticoagulant drugs (warfarin), inotropic drugs (dicitalis preparations), platelet adhesion inhibitors, antiarrhythmic drugs (quinidine), Pharmacological treatments for administering diuretic antihypertensive drugs (trichlormethiazide, furosemide), antihyperlipidemic drugs and the like to patients are known.
【０００５】また、薬物療法以外の治療法としては、新
しい血管の道をつくる冠状動脈バイパス手術(CABG)、侵
襲の少ない経皮的冠状動脈形成術(PTCA) 、再狭窄を防
止するためのステントを留置する手術などの外科的療法
が、知られている。[0005] Treatments other than drug therapy include coronary artery bypass surgery (CABG) for creating new blood vessel tracts, less invasive percutaneous coronary angioplasty (PTCA), and stents for preventing restenosis. Surgical treatments, such as surgery to indwell, are known.
【０００６】しかしながら、これらの治療法は、根本的
に心臓の障害を改善するものではなく、これらの治療に
より疾患が寛解することは少ない。また、拡張型心筋症
や肥大型心筋症は、これらの方法では有効に治療でき
ず、心臓移植による治療しかない。[0006] However, these treatments do not fundamentally ameliorate cardiac disorders, and these treatments rarely ameliorate the disease. In addition, dilated cardiomyopathy and hypertrophic cardiomyopathy cannot be treated effectively by these methods, but only by heart transplantation.
【０００７】しかし、心臓移植は、拒絶反応やドナー不
足が大きな問題となっており、現段階では、心臓移植を
行うには限界がある。However, heart transplantation has a serious problem of rejection and a shortage of donors, and there is a limit in performing heart transplantation at this stage.
【０００８】ところで、近年、基礎医学研究は、臓器や
細胞レベルから遺伝子、分子生物学レベルへと急速な展
開を遂げている。このため、医学の分野では、生命現象
や病態を分子生物学レベルで把握することが可能となっ
てきた。そして、心臓疾患においても、病態把握、およ
び発症機序の解明が、分子生物学レベルで可能となって
きている。In recent years, basic medical research has rapidly progressed from the level of organs and cells to the level of gene and molecular biology. For this reason, in the field of medicine, it has become possible to grasp life phenomena and pathological conditions at the molecular biology level. Also in the case of heart disease, it is becoming possible to understand the pathological condition and elucidate the pathogenesis at the molecular biology level.
【０００９】これにともない、現在、分子生物学レベル
の基礎研究をもとにした新しい心臓疾患の治療法が、開
発されつつある。Accordingly, a new treatment for heart disease based on basic research at the molecular biology level is being developed.
【００１０】しかしながら、心臓移植等、従来の心臓疾
患の治療法に用いられる従来の投薬装置では、このよう
な治療法に対応することができない。このため、このよ
うな新しい治療法を効果的に行うために、新しい治療法
に対応した新しい投薬装置の開発が必要となってきてい
る。However, a conventional medication device used for a conventional method of treating a heart disease such as a heart transplant cannot cope with such a method of treatment. Therefore, in order to effectively carry out such a new treatment method, it is necessary to develop a new medication device corresponding to the new treatment method.
【００１１】[0011]
【発明が解決しようとする課題】本発明の目的は、例え
ば心臓に対する遺伝子治療等を好適に行うことができる
薬物投与装置を提供することにある。SUMMARY OF THE INVENTION An object of the present invention is to provide a drug administration device capable of suitably performing, for example, gene therapy on the heart.
【００１２】[0012]
【課題を解決するための手段】このような目的は、下記
（１）〜（１７）の本発明により達成される。This and other objects are achieved by the present invention which is defined below as (1) to (17).
【００１３】（１） 生体内に薬物を投与する薬物投与
装置であって、薬物を循環させる循環ラインと、第１の
薬物を前記循環ラインに供給する第１の薬物供給手段
と、第２の薬物を前記循環ラインに供給する第２の薬物
供給手段とを有することを特徴とする薬物投与装置。(1) A drug administration device for administering a drug into a living body, comprising: a circulating line for circulating the drug; first drug supply means for supplying a first drug to the circulating line; A second drug supply unit for supplying a drug to the circulation line.
【００１４】（２） 前記第１の薬物供給手段は、前記
循環ラインの流路の途中に設置されたリザーバーと、該
リザーバーに接続され、前記第１の薬物を貯留する貯留
部とを有する上記（１）に記載の薬物投与装置。(2) The first drug supply means has a reservoir installed in the middle of the flow path of the circulation line, and a storage unit connected to the reservoir and storing the first drug. The drug administration device according to (1).
【００１５】（３） 前記循環ラインから分岐するバイ
パスラインを有し、前記第２の薬物供給手段は、前記バ
イパスライン上に設けられている上記（１）または
（２）に記載の薬物投与装置。(3) The drug administration device according to (1) or (2), further comprising a bypass line branched from the circulation line, wherein the second drug supply unit is provided on the bypass line. .
【００１６】（４） 前記第２の薬物供給手段は、リザ
ーバーと、該リザーバーに接続され、前記第２の薬物を
貯留する貯留部とを有する上記（１）ないし（３）のい
ずれかに記載の薬物投与装置。(4) The second drug supply means according to any one of the above (1) to (3), wherein the second drug supply means has a reservoir and a storage section connected to the reservoir and storing the second drug. Drug administration device.
【００１７】（５） 前記循環ラインから分岐するバイ
パスラインを有し、前記リザーバーは、前記バイパスラ
インの流路の途中に設置されている上記（４）に記載の
薬物投与装置。(5) The drug administration device according to the above (4), further comprising a bypass line branching from the circulation line, wherein the reservoir is provided in the middle of the flow path of the bypass line.
【００１８】（６） 前記第１の薬物供給手段への流路
と前記第２の薬物供給手段への流路とを切り換える流路
切り換え手段を有する上記（１）ないし（５）のいずれ
かに記載の薬物投与装置。(6) Any of (1) to (5) above, further comprising a flow path switching means for switching a flow path to the first drug supply means and a flow path to the second drug supply means. The drug administration device according to claim 1.
【００１９】（７） 前記第１のおよび／または第２の
薬物の温度を調整する温度調整手段を有する上記（１）
ないし（６）のいずれかに記載の薬物投与装置。(7) The above (1) having a temperature adjusting means for adjusting the temperature of the first and / or second drug.
The drug administration device according to any one of (1) to (6).
【００２０】（８） 前記温度調整手段は、前記第１の
薬物供給手段および前記第２の薬物供給手段よりも下流
側の前記循環ライン上に設けられている上記（７）に記
載の薬物投与装置。(8) The drug administration according to (7), wherein the temperature adjustment means is provided on the circulation line downstream of the first drug supply means and the second drug supply means. apparatus.
【００２１】（９） 前記薬物を生体内に注入する注入
ラインを有する上記（１）ないし（８）のいずれかに記
載の薬物投与装置。(9) The drug administration device according to any one of (1) to (8), further including an injection line for injecting the drug into a living body.
【００２２】（１０） 前記第１の薬物を生体内に投与
した後、前記第２の薬物を生体内に投与する上記（１）
ないし（９）のいずれかに記載の薬物投与装置。(10) The method according to (1), wherein after the first drug is administered to the living body, the second drug is administered to the living body.
The drug administration device according to any one of (9) to (9).
【００２３】（１１） 前記第１の薬物が、前記第２の
薬物の薬効を助長、および／または、前記第２の薬物の
副作用を抑制する上記（１）ないし（１０）のいずれか
に記載の薬物投与装置。(11) The method according to any one of (1) to (10), wherein the first drug promotes the efficacy of the second drug and / or suppresses a side effect of the second drug. Drug administration device.
【００２４】（１２） 前記第１の薬物は、心臓の細胞
を保護する薬である上記（１）ないし（１１）のいずれ
かに記載の薬物投与装置。(12) The drug administration device according to any one of (1) to (11), wherein the first drug is a drug for protecting heart cells.
【００２５】（１３） 前記第１の薬物は、心筋保護薬
である上記（１）ないし（１２）のいずれかに記載の薬
物投与装置。(13) The drug administration device according to any one of the above (1) to (12), wherein the first drug is a cardioprotective drug.
【００２６】（１４） 前記第２の薬物は、心臓の細胞
を治療する薬である上記（１）ないし（１３）のいずれ
かに記載の薬物投与装置。(14) The drug administration device according to any one of (1) to (13), wherein the second drug is a drug for treating cells of the heart.
【００２７】（１５） 前記第２の薬物は、遺伝子治療
薬である上記（１）ないし（１４）のいずれかに記載の
薬物投与装置。(15) The drug administration device according to any one of the above (1) to (14), wherein the second drug is a gene therapy drug.
【００２８】（１６） 生体内に薬物を注入する注入ラ
インを有し、該注入ラインを介して心臓を停止させるた
めの薬物を生体内に注入し、次いで、遺伝子治療薬を生
体内に注入するように構成されたことを特徴とする薬物
投与装置。(16) There is an injection line for injecting a drug into the living body, a drug for stopping the heart is injected into the living body via the injection line, and then a gene therapy drug is injected into the living body. A drug administration device characterized by being configured as described above.
【００２９】（１７） 薬物の温度を調整する温度調整
手段を有し、この温度調整手段を用いて前記心臓を停止
させるための薬物または前記遺伝子治療薬の少なくとも
一方の温度を調整して、前記心臓を停止させるための薬
物および前記遺伝子治療薬を生体内に注入することがで
きる上記（１６）に記載の薬物投与装置。(17) There is provided temperature adjusting means for adjusting the temperature of the drug, and the temperature adjusting means is used to adjust the temperature of at least one of the drug for stopping the heart or the gene therapy drug. The drug administration device according to the above (16), which is capable of injecting a drug for stopping the heart and the gene therapy drug into a living body.
【００３０】[0030]
【発明の実施の形態】以下、本発明を添付図面に示す好
適実施形態に基づいて詳細に説明する。図１は、本発明
の薬物投与装置の実施形態を示す回路図である。DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be described in detail based on preferred embodiments shown in the accompanying drawings. FIG. 1 is a circuit diagram showing an embodiment of the drug administration device of the present invention.
【００３１】本発明の薬物投与装置１は、生体内に薬物
を投与する装置である。図１に示すように、薬物投与装
置１は、薬物を循環（灌流）させる循環ライン２と、か
かる循環ライン２から分岐したバイパスライン（分岐ラ
イン）３と、循環ライン２に接続された注入ライン９お
よびベントライン１００とを有している。循環ライン２
には、上流側から順に、第１三方活栓８１と、心筋保護
剤供給手段（第１の薬物供給手段）４と、第２三方活栓
８２と、ポンプ２１と、温度調整手段６と、切り換えバ
ルブ７とが設けられている。また、バイパスライン３に
は、遺伝子治療薬供給手段（第２の薬物供給手段）５が
設けられている。The drug administration device 1 of the present invention is a device for administering a drug into a living body. As shown in FIG. 1, the drug administration device 1 includes a circulation line 2 for circulating (perfusing) a drug, a bypass line (branch line) 3 branched from the circulation line 2, and an injection line connected to the circulation line 2. 9 and a vent line 100. Circulation line 2
The first three-way cock 81, the myocardial protective agent supply means (first drug supply means) 4, the second three-way cock 82, the pump 21, the temperature adjusting means 6, the switching valve 7 are provided. Further, the bypass line 3 is provided with a gene therapy drug supply unit (second drug supply unit) 5.
【００３２】この薬物投与装置１を用いて、例えば、患
者の体内に心筋保護剤と遺伝子治療薬とを投与し、遺伝
子治療を行い、心臓疾患を治療することができる。まず
始めに、循環ライン２から説明する。Using this drug administration device 1, for example, a cardioprotective agent and a gene therapy drug can be administered into a patient's body, gene therapy can be performed, and a heart disease can be treated. First, the circulation line 2 will be described.
【００３３】循環ライン２は、薬物投与装置１の主要構
成部材が設置あるいは接続されたラインであり、前述し
たように、上流側から順に、第１三方活栓８１と、心筋
保護剤供給手段４と、第２三方活栓８２と、ポンプ２１
と、温度調整手段６と、切り換えバルブ７とを有してい
る。The circulating line 2 is a line in which the main components of the drug administration device 1 are installed or connected. As described above, the first three-way cock 81, the myocardial protective agent supplying means 4, , The second three-way cock 82 and the pump 21
, A temperature adjusting means 6 and a switching valve 7.
【００３４】以下、説明の便宜上、循環ライン２のう
ち、第１三方活栓８１よりも上流側の流域を「上流域２
６」、第１三方活栓８１と第２三方活栓８２との間の流
域を「中流域２７」、第２三方活栓８２よりも下流側の
流域を「下流域２８」という。Hereinafter, for convenience of explanation, the basin of the circulation line 2 upstream of the first three-way cock 81 will be referred to as “upstream area 2”.
6 ", a basin between the first three-way cock 81 and the second three-way cock 82 is referred to as a" medium basin 27 ", and a basin downstream of the second three-way cock 82 is referred to as a" downstream area 28 ".
【００３５】図１に示すように、中流域２７には、循環
ライン２に心筋保護剤（第１の薬物）を供給する心筋保
護剤供給手段４が設置されている。この心筋保護剤供給
手段４は、循環ライン２上に設置された第１リザーバー
４１と、かかる第１リザーバー４１に接続された心筋保
護剤貯留部（第１の薬物を貯留する貯留部）４３とで構
成されている。As shown in FIG. 1, a myocardial protective agent supplying means 4 for supplying a myocardial protective agent (first drug) to the circulation line 2 is provided in the middle stream area 27. The myocardial protective agent supply means 4 includes a first reservoir 41 installed on the circulation line 2, a myocardial protective agent storage unit (a storage unit for storing a first drug) 43 connected to the first reservoir 41, It is composed of
【００３６】心筋保護剤貯留部４３は、心筋保護剤を貯
留する部分であり、例えば容器等で構成されている。こ
の心筋保護剤貯留部４３から第１リザーバー４１に、必
要に応じて適宜、心筋保護剤が供給される。第１リザー
バー４１は、心筋保護剤を一時的に貯留することができ
る。心筋保護剤貯留部４３の容積は、特に限定されない
が、例えば１０００〜３０００mL程度とすることが好ま
しい。また、第１リザーバー４１の容積は、特に限定さ
れないが、例えば１０００〜５０００mL程度とすること
が好ましい。なお、第１リザーバー４１と心筋保護剤貯
留部４３との間に、開閉を選択するまたは開度を調節す
るバルブを設けていてもよい。The myocardial protective agent storage section 43 is a section for storing a myocardial protective agent, and is composed of, for example, a container. The myocardial protective agent is supplied from the myocardial protective agent storage section 43 to the first reservoir 41 as needed. The first reservoir 41 can temporarily store the cardioplegic agent. The volume of the myocardial protective agent storage section 43 is not particularly limited, but is preferably, for example, about 1000 to 3000 mL. The volume of the first reservoir 41 is not particularly limited, but is preferably, for example, about 1000 to 5000 mL. It should be noted that a valve for selecting opening or closing or adjusting the opening may be provided between the first reservoir 41 and the myocardial protective agent reservoir 43.
【００３７】心筋保護剤供給手段４の下流側には、循環
ライン２またはバイパスライン３内の薬物を循環させる
ポンプ２１が設けられている。A pump 21 for circulating the drug in the circulation line 2 or the bypass line 3 is provided downstream of the myocardial protective agent supply means 4.
【００３８】さらにこのポンプ２１の下流側には、薬物
投与装置１内を循環する薬物の温度を調整する温度調整
手段６が設置されている。かかる温度調整手段６は、熱
媒／冷媒を用いて下流域２８を流れる薬物の温度を調整
するような構成となっており、循環ライン２上に設置さ
れた熱交換器６１と、熱媒／冷媒の温度を調整する温度
調整機６３と、熱交換器６１と温度調整機６３との間で
熱媒／冷媒を循環させる熱交換ライン６２とを有してい
る。この温度調整手段６で、薬物の温度を例えば０〜２
０℃程度に冷却したり、あるいは、体温程度に加温した
りすることができる。Further, a temperature adjusting means 6 for adjusting the temperature of the drug circulating in the drug administration device 1 is provided downstream of the pump 21. The temperature adjusting means 6 is configured to adjust the temperature of the drug flowing in the downstream region 28 using a heat medium / coolant, and includes a heat exchanger 61 installed on the circulation line 2 and a heat medium / coolant. It has a temperature controller 63 for adjusting the temperature of the refrigerant, and a heat exchange line 62 for circulating the heat medium / refrigerant between the heat exchanger 61 and the temperature controller 63. The temperature of the drug is controlled by, for example, 0 to 2
It can be cooled to about 0 ° C. or heated to about body temperature.
【００３９】このように、温度調整手段６を設けると、
最も治療効果が得られるような温度に薬物の温度を調整
してから、薬物を患者の体内に投与できるようになる。
特に、温度調整手段６を下流域２８、すなわち心筋保護
剤供給手段４および遺伝子治療薬供給手段５の下流側に
設置すると、温度調整手段６で心筋保護剤および遺伝子
治療薬の両方の温度を好適に調整することができるよう
になる。しかも、薬物投与装置１の構成を簡易なものと
することができる。また、温度調整手段６を下流域２８
に設置すると、患者に投与される直前に薬物の温度が調
整されるようになり、薬物の温度調整の精度が向上す
る。As described above, when the temperature adjusting means 6 is provided,
After adjusting the temperature of the drug to a temperature at which the therapeutic effect is obtained most, the drug can be administered to the patient.
In particular, when the temperature adjusting means 6 is installed in the downstream region 28, that is, on the downstream side of the myocardial protective agent supplying means 4 and the gene therapeutic agent supplying means 5, the temperature adjusting means 6 suitably controls the temperatures of both the myocardial protective agent and the gene therapeutic agent. Can be adjusted. Moreover, the configuration of the drug administration device 1 can be simplified. Further, the temperature adjusting means 6 is connected to the downstream region 28.
In this case, the temperature of the drug is adjusted immediately before being administered to the patient, and the accuracy of adjusting the temperature of the drug is improved.
【００４０】温度調整手段６の下流側には、切り換えバ
ルブ７が設けられている。この切り換えバルブ７には、
生体内に薬物（心筋保護剤および遺伝子治療薬）を注入
する注入ライン（例えば心臓カテーテル）９と、生体内
の薬物を排出するために用いられるベントライン１００
とが接続されている。そして、切り換えバルブ７によ
り、例えば、下流域２８またはベントライン１００を、
上流域２６または注入ライン９に、接続することができ
る。すなわち、薬物投与装置１は、切り換えバルブ７に
より、薬物の流路を、薬物が薬物投与装置１内を循環す
る流路と、薬物を生体内に供給する流路と、薬物が生体
内を経由して薬物投与装置１内を循環する（薬物が生体
内と薬物投与装置１との間を循環する）流路等とに切り
換えることができる。A switching valve 7 is provided downstream of the temperature adjusting means 6. This switching valve 7 includes:
An injection line (for example, a cardiac catheter) 9 for injecting a drug (a cardioprotective agent and a gene therapy drug) into a living body, and a vent line 100 used for discharging the drug in the living body
And are connected. Then, for example, the downstream region 28 or the vent line 100 is switched by the switching valve 7.
It can be connected to the upstream zone 26 or the injection line 9. That is, the drug administration device 1 uses the switching valve 7 to change the flow path of the drug, the flow channel in which the drug circulates in the drug administration device 1, the flow channel for supplying the drug into the living body, and the drug passing through the living body. Then, it can be switched to a flow path or the like that circulates in the drug administration device 1 (drug circulates between the living body and the drug administration device 1).
【００４１】このような循環ライン２では、心筋保護剤
供給手段４の上流側にポート８１１を有する第１三方活
栓８１が、また、心筋保護剤供給手段４の下流側にポー
ト８２１を有する第２三方活栓８２が設置されている。
そして、第１三方活栓８１には、バイパスライン３の上
流（上流３６）端が、第２三方活栓８２には、バイパス
ライン３の下流（下流３７）端が接続されている。In such a circulation line 2, a first three-way cock 81 having a port 811 on the upstream side of the myocardial protective agent supply means 4 and a second three-way cock 81 having a port 821 on the downstream side of the myocardial protective agent supply means 4. A three-way cock 82 is provided.
The upstream (upstream 36) end of the bypass line 3 is connected to the first three-way cock 81, and the downstream (downstream 37) end of the bypass line 3 is connected to the second three-way cock 82.
【００４２】これら第１三方活栓８１および第２三方活
栓８２により、循環ライン２の中流域２７とバイパスラ
イン３との間で、流路を切り換えることができる。な
お、薬物投与装置１では、第１三方活栓８１と第２三方
活栓８２とで、心筋保護剤供給手段４への流路と遺伝子
治療薬供給手段５への流路とを切り換える流路切り換え
手段８が構成されている。なお、ポート８１１およびポ
ート８２１は、例えば、他の薬液の混注、排出、サンプ
リングなどに用いることができる。With the first three-way cock 81 and the second three-way cock 82, the flow path can be switched between the midstream area 27 of the circulation line 2 and the bypass line 3. In the drug administration device 1, the first three-way cock 81 and the second three-way cock 82 switch between a flow path to the myocardial protective agent supply means 4 and a flow path to the gene therapy drug supply means 5. 8 are configured. The port 811 and the port 821 can be used for, for example, co-injection, discharge, sampling, and the like of another chemical solution.
【００４３】循環ライン２から分岐した（分岐し再び合
流する）バイパスライン３上には、循環ライン２に遺伝
子治療薬（第２の薬物）を供給する遺伝子治療薬供給手
段５が設けられている。この遺伝子治療薬供給手段５
は、バイパスライン３上に設置された第２リザーバー５
１と、かかる第２リザーバー５１に接続された遺伝子治
療薬貯留部（第２の薬物を貯留する貯留部）５３とで構
成されている。On the bypass line 3 branched from the circulation line 2 (branch and merge again), a gene therapy drug supply means 5 for supplying a gene therapy drug (second drug) to the circulation line 2 is provided. . This gene therapy drug supply means 5
Is the second reservoir 5 installed on the bypass line 3
1 and a gene therapy drug storage section (a storage section for storing a second drug) 53 connected to the second reservoir 51.
【００４４】遺伝子治療薬貯留部５３は、遺伝子治療薬
を貯留する部分であり、例えば容器等で構成されてい
る。この遺伝子治療薬貯留部５３から第２リザーバー５
１に、必要に応じて適宜、遺伝子治療薬が供給される。
この第２リザーバー５１は、遺伝子治療薬を一時的に貯
留することができる。遺伝子治療薬貯留部５３の容積
は、特に限定されないが、例えば１００〜２０００mL程
度とすることが好ましい。また、第２リザーバー５１の
容積は、特に限定されないが、例えば５００〜５０００
mL程度とすることが好ましい。なお、第２リザーバー５
１と遺伝子治療薬貯留部５３との間に、開閉を選択する
または開度を調節するバルブを設けていてもよい。The gene therapy drug storage section 53 is a section for storing the gene therapy drug, and is composed of, for example, a container. From the gene therapy drug reservoir 53 to the second reservoir 5
1, a gene therapy drug is supplied as needed.
This second reservoir 51 can temporarily store the gene therapy drug. The volume of the gene therapy drug reservoir 53 is not particularly limited, but is preferably, for example, about 100 to 2000 mL. The volume of the second reservoir 51 is not particularly limited, but is, for example, 500 to 5000.
It is preferably about mL. In addition, the second reservoir 5
A valve for selecting opening or closing or adjusting the opening degree may be provided between 1 and the gene therapy drug reservoir 53.
【００４５】以下、薬物投与装置１の作用を、心臓疾患
に対する遺伝子治療を行う場合を例に、説明する。以下
の作用を端的に言うと、本発明の薬物投与装置１を用い
て、まず、心筋保護剤を患者に投与することにより、遺
伝子治療薬の薬効を助長し、かつ遺伝子治療薬の副作用
を抑制できるような環境を患者の体内に作り出してか
ら、遺伝子治療薬を、患者に投与して、治療を行う。The operation of the drug administration device 1 will be described below, taking as an example the case of performing gene therapy for heart disease. Briefly, the following effects are firstly administered to a patient using a drug administration device 1 of the present invention, thereby promoting the efficacy of the gene therapy drug and suppressing the side effects of the gene therapy drug. After creating an environment that can be created in the patient's body, a gene therapy drug is administered to the patient to perform treatment.
【００４６】薬物投与装置１を使用するに先だって、あ
るいは薬物投与装置１の使用と平行して、あらかじめ、
患者に人工心肺装置もしくは経皮的心肺補助装置（ＰＣ
ＰＳ）を接続し、これらの人工心肺装置もしくは経皮的
心肺補助装置（ＰＣＰＳ）を作動させておく。すなわ
ち、薬物投与装置１を使用するに先だって、あるいは薬
物投与装置１の使用と平行して、あらかじめ、患者の心
臓および肺の機能を、人工心肺装置もしくは経皮的心肺
補助装置（ＰＣＰＳ）に代行させておく。Prior to using the drug administration device 1 or in parallel with the use of the drug administration device 1,
Patients receive a heart-lung machine or a percutaneous cardiopulmonary assist device (PC
PS), and operate these cardiopulmonary bypass devices or percutaneous cardiopulmonary support devices (PCPS). That is, prior to or in parallel with the use of the drug administration device 1, the function of the patient's heart and lungs is previously substituted by a heart-lung machine or a percutaneous cardiopulmonary assist device (PCPS). Let it be.
【００４７】なお、薬物投与装置１に対しては、あらか
じめ、循環路（循環ライン２およびバイパスライン３）
のプライミングを生理食塩水等で行っておくことが好ま
しい。この場合のプライミング量は、特に限定されない
が、例えば、５００〜２０００mL程度とすることが好ま
しい。The drug administration device 1 has a circulation path (circulation line 2 and bypass line 3) in advance.
It is preferable to perform priming with physiological saline or the like. The priming amount in this case is not particularly limited, but is preferably, for example, about 500 to 2000 mL.
【００４８】その後、薬物投与装置１では、心筋保護剤
供給手段４への流路を開放し、遺伝子治療薬供給手段５
への流路は遮断しておく。具体的には、第１三方活栓８
１では、上流域２６から中流域２７への流路は開放して
おき、上流域２６からバイパスライン３への流路は遮断
しておく。また、第２三方活栓８２では、中流域２７か
ら下流域２８への流路は開放しておき、バイパスライン
３から下流域２８への流路は遮断しておく。さらには、
切り換えバルブ７では、下流域２８から上流域２６への
流路は開放しておき、下流域２８から注入ライン９への
流路は遮断しておく。Thereafter, in the drug administration device 1, the flow path to the cardioplegic agent supply means 4 is opened, and the gene therapy drug supply means 5 is opened.
The flow path to is shut off. Specifically, the first three-way cock 8
In 1, the flow path from the upstream area 26 to the middle flow area 27 is open, and the flow path from the upstream area 26 to the bypass line 3 is shut off. In the second three-way cock 82, the flow path from the middle flow area 27 to the downstream area 28 is open, and the flow path from the bypass line 3 to the downstream area 28 is shut off. Moreover,
In the switching valve 7, the flow path from the downstream area 28 to the upstream area 26 is open, and the flow path from the downstream area 28 to the injection line 9 is shut off.
【００４９】また、心筋保護剤貯留部４３に心筋保護剤
（心臓の細胞を保護する薬）を、遺伝子治療薬貯留部５
３に遺伝子治療薬（心臓の細胞を治療する薬）を、それ
ぞれ貯留しておく。The myocardial protective agent reservoir (drug for protecting cells of the heart) is stored in the myocardial protective agent reservoir 43.
Third, a gene therapy drug (a drug for treating cells of the heart) is stored.
【００５０】また、温度調整手段６を作動させておく。
温度調整手段６を作動させると、冷媒が熱交換ライン６
２内、すなわち温度調整機６３と熱交換器６１との間を
循環する。そして、この冷媒が温度調整機６３を通過す
るとき、冷媒の設定温度に冷却される。Further, the temperature adjusting means 6 is operated.
When the temperature adjusting means 6 is operated, the refrigerant is transferred to the heat exchange line 6.
2, that is, between the temperature controller 63 and the heat exchanger 61. Then, when this refrigerant passes through the temperature controller 63, it is cooled to the set temperature of the refrigerant.
【００５１】まず、注入ライン９を、例えば患者の心
臓、大動脈、冠動脈など、患者の心臓または心臓近傍
（目的部位）に接続する。そして、ベントライン１００
を、例えば患者の肺動脈、左心室尖部など、患者の心臓
または心臓近傍（目的部位）に接続する。次に、心筋保
護剤貯留部４３から第１リザーバー４１に心筋保護剤を
供給し、第１リザーバー４１内に心筋保護剤を充填す
る。First, the injection line 9 is connected to the patient's heart or the vicinity of the heart (target site), for example, the patient's heart, aorta, coronary artery, or the like. And the vent line 100
Is connected to the patient's heart or the vicinity of the heart (target site), for example, the pulmonary artery of the patient or the apex of the left ventricle. Next, the myocardial protective agent is supplied from the myocardial protective agent storage section 43 to the first reservoir 41, and the first reservoir 41 is filled with the myocardial protective agent.
【００５２】次に、ポンプ２１を作動させる。これによ
り、第１リザーバー４１内の心筋保護剤は、所定の流速
で、循環ライン２内を循環する。具体的には、第１リザ
ーバー４１から流出した心筋保護剤は、第２三方活栓８
２、ポンプ２１、熱交換器６１、切り換えバルブ７、第
１三方活栓８１を通り、第１リザーバー４１内に再流入
する。Next, the pump 21 is operated. Thereby, the myocardial protective agent in the first reservoir 41 circulates in the circulation line 2 at a predetermined flow rate. Specifically, the myocardial protective agent that has flowed out of the first reservoir 41 is the second three-way cock 8.
2. Re-flows into the first reservoir 41 through the pump 21, the heat exchanger 61, the switching valve 7, and the first three-way cock 81.
【００５３】このとき、心筋保護剤が熱交換器６１を通
過する際に、熱交換器６１内の冷媒と心筋保護剤との間
で熱交換が行われる。このため、心筋保護剤は、熱交換
器６１を通過する際に、設定温度に冷却される。特に、
心筋保護剤の温度を、好ましくは０〜１５℃程度、より
好ましくは４〜８℃程度に調整すると、より好適に患者
を治療できるようになる。At this time, when the myocardial protective agent passes through the heat exchanger 61, heat is exchanged between the refrigerant in the heat exchanger 61 and the myocardial protective agent. Therefore, the myocardial protective agent is cooled to the set temperature when passing through the heat exchanger 61. In particular,
When the temperature of the cardioplegic agent is adjusted to preferably about 0 to 15 ° C, more preferably about 4 to 8 ° C, the patient can be more appropriately treated.
【００５４】その後、切り換えバルブ７の流路を切り換
え、下流域２８から注入ライン９への流路を開放し、下
流域２８から上流域２６への流路を遮断する。これによ
り、心筋保護剤が、下流域２８から、切り換えバルブ
７、注入ライン９を通り、患者の体内に注入される。心
筋保護剤が患者の体内に注入されると、心筋保護剤は患
者の心臓に到達し、患者の心臓が停止する。Thereafter, the flow path of the switching valve 7 is switched, the flow path from the downstream area 28 to the injection line 9 is opened, and the flow path from the downstream area 28 to the upstream area 26 is shut off. As a result, the myocardial protective agent is injected into the patient from the downstream region 28 through the switching valve 7 and the injection line 9. When the cardioprotective agent is injected into the patient's body, the cardioprotective agent reaches the patient's heart and the patient's heart stops.
【００５５】次に、切り換えバルブ７の流路を切り換
え、下流域２８から上流域２６への流路を開放し、下流
域２８から注入ライン９への流路を遮断する。Next, the flow path of the switching valve 7 is switched, the flow path from the downstream area 28 to the upstream area 26 is opened, and the flow path from the downstream area 28 to the injection line 9 is shut off.
【００５６】また、遺伝子治療薬貯留部５３から第２リ
ザーバー５１に遺伝子治療薬を供給し、第２リザーバー
５１内に遺伝子治療薬を充填する。The gene therapy drug is supplied from the gene therapy drug storage section 53 to the second reservoir 51, and the second reservoir 51 is filled with the gene therapy drug.
【００５７】次に、流路切り換え手段８を操作し、遺伝
子治療薬供給手段５への流路を開放し、心筋保護剤供給
手段４への流路を遮断する。具体的には、第１三方活栓
８１を操作し、上流域２６からバイパスライン３への流
路を開放し、上流域２６から中流域２７への流路を遮断
する。また、第２三方活栓８２も操作し、バイパスライ
ン３から下流域２８への流路を開放し、中流域２７から
下流域２８への流路を遮断する。この際、第１三方活栓
８１または第２三方活栓８２を操作し、ポート８１１ま
たはポート８２１から、不要となった心筋保護剤を、外
部に排出してもよい。Next, the flow path switching means 8 is operated to open the flow path to the gene therapy drug supply means 5 and cut off the flow path to the myocardial protective agent supply means 4. Specifically, the first three-way cock 81 is operated to open the flow path from the upstream area 26 to the bypass line 3 and shut off the flow path from the upstream area 26 to the middle flow area 27. Further, the second three-way cock 82 is also operated to open the flow path from the bypass line 3 to the downstream area 28 and shut off the flow path from the middle flow area 27 to the downstream area 28. At this time, the first three-way cock 81 or the second three-way cock 82 may be operated to discharge the unnecessary myocardial protective agent from the port 811 or the port 821 to the outside.
【００５８】これにより、第２リザーバー５１内の遺伝
子治療薬が、所定の流速で、バイパスライン３、下流域
２８および上流域２６内を循環する。具体的には、第２
リザーバー５１から流出した遺伝子治療薬は、第２三方
活栓８２、ポンプ２１、熱交換器６１、切り換えバルブ
７、第１三方活栓８１を通り、第２リザーバー５１内に
再流入する。As a result, the gene therapy drug in the second reservoir 51 circulates at a predetermined flow rate in the bypass line 3, the downstream region 28 and the upstream region 26. Specifically, the second
The gene therapy drug that has flowed out of the reservoir 51 passes through the second three-way cock 82, the pump 21, the heat exchanger 61, the switching valve 7, and the first three-way cock 81, and flows back into the second reservoir 51.
【００５９】このとき、遺伝子治療薬が熱交換器６１を
通過する際に、熱交換器６１内の冷媒と遺伝子治療薬と
の間で熱交換が行われる。このため、遺伝子治療薬は、
熱交換器６１を通過する際に、設定温度に冷却される。
特に、遺伝子治療薬の温度を、好ましくは０〜２０℃程
度、より好ましくは４〜８℃程度に調整すると、より好
適に遺伝子治療を行えるようになる。At this time, when the gene therapy drug passes through the heat exchanger 61, heat exchange is performed between the refrigerant in the heat exchanger 61 and the gene therapy drug. For this reason, gene therapy drugs
When passing through the heat exchanger 61, it is cooled to the set temperature.
In particular, when the temperature of the gene therapy drug is adjusted to preferably about 0 to 20 ° C, more preferably about 4 to 8 ° C, gene therapy can be performed more suitably.
【００６０】その後、切り換えバルブ７の流路を切り換
え、下流域２８から注入ライン９への流路を開放し、下
流域２８から上流域２６への流路を遮断する。これによ
り、遺伝子治療薬が、下流域２８から、切り換えバルブ
７、注入ライン９を通り、患者の体内に注入される。遺
伝子治療薬が患者の体内に注入されると、遺伝子治療薬
は患者の心臓に到達する。そして、患者の心臓は、この
遺伝子治療薬により治療されることとなる。Thereafter, the flow path of the switching valve 7 is switched, the flow path from the downstream area 28 to the injection line 9 is opened, and the flow path from the downstream area 28 to the upstream area 26 is shut off. As a result, the gene therapy drug is injected from the downstream area 28 into the patient through the switching valve 7 and the injection line 9. When the gene therapy drug is injected into the patient, the gene therapy drug reaches the patient's heart. Then, the patient's heart is to be treated with the gene therapy drug.
【００６１】さらに、心臓内での遺伝子治療薬の有効濃
度を高く維持するためには、切り換えバルブ７を操作
し、注入ライン９とベントライン１００とを開放し、心
臓と薬物投与装置１との間（例えば心臓とベントライン
１００と切り換えバルブ７と注入ライン９との間、ある
いは、心臓とベントライン１００と切り換えバルブ７と
上流域２６とバイパスライン３と下流域２８と注入ライ
ン９との間）で遺伝子治療薬を循環させる。その時、遺
伝子治療薬貯留部５３のフレッシュな遺伝子治療薬を、
第２リザーバー５１に供給して、循環させても良い。Further, in order to keep the effective concentration of the gene therapy drug high in the heart, the switching valve 7 is operated, the injection line 9 and the vent line 100 are opened, and the connection between the heart and the drug administration device 1 is established. Between (for example, between the heart and the vent line 100 and the switching valve 7 and the injection line 9 or between the heart and the vent line 100 and the switching valve 7 and between the upstream region 26, the bypass line 3, the downstream region 28 and the injection line 9). ) To circulate the gene therapy drug. At that time, the fresh gene therapy drug in the gene therapy drug reservoir 53
It may be supplied to the second reservoir 51 and circulated.
【００６２】その後、患者の体内から、遺伝子治療薬を
排出する。さらには、患者の心臓の鼓動を再開させる。Thereafter, the gene therapy drug is discharged from the patient's body. Further, the heartbeat of the patient is resumed.
【００６３】なお、以上の説明では、温度調整手段６に
冷媒を用い、心筋保護剤および遺伝子治療薬を冷却した
が、必要に応じて冷媒の代わりに熱媒を用い、心筋保護
剤および遺伝子治療薬を加温してもよい。In the above description, the myocardial protective agent and the gene therapy agent were cooled by using a refrigerant for the temperature adjusting means 6, but the myocardial protective agent and the gene therapy agent were substituted by a heat medium instead of the refrigerant as necessary. The drug may be warmed.
【００６４】このように、本発明の薬物投与装置１を用
いれば、まず、心筋保護剤を患者の心臓に投与し、患者
の心臓を停止させた後、遺伝子治療薬を患者に投与する
ことができる。したがって、本発明の薬物投与装置１を
用いれば、遺伝子治療薬を、患者の心臓に、局所的に投
与することができ、遺伝子治療薬が、全身に拡散しにく
い。このため、本発明の薬物投与装置１を用いれば、他
の生体組織、臓器に、大きな副作用、悪影響を与えず
に、心臓に対して遺伝子治療を施すことができる。加え
て、本発明の薬物投与装置１を用いれば、遺伝子治療薬
を患者の心臓に局所的に投与することができるので、遺
伝子治療薬の投与量を少なくしても、薬効、治療効果が
得られるようになる。As described above, when the drug administration device 1 of the present invention is used, first, the cardioprotective agent is administered to the patient's heart, the patient's heart is stopped, and then the gene therapy drug is administered to the patient. it can. Therefore, by using the drug administration device 1 of the present invention, the gene therapy drug can be locally administered to the patient's heart, and the gene therapy drug is unlikely to spread throughout the body. Therefore, with the use of the drug administration device 1 of the present invention, gene therapy can be performed on the heart without causing significant side effects or adverse effects on other living tissues and organs. In addition, by using the drug administration device 1 of the present invention, the gene therapy drug can be locally administered to the patient's heart, so that even if the dose of the gene therapy drug is reduced, the medicinal and therapeutic effects can be obtained. Will be able to
【００６５】また、本発明の薬物投与装置１のように、
循環ライン２を設け、かかる循環ライン２内を薬物が循
環するようにすると、継続的にフレッシュな薬物を患者
に投与することが可能となる。しかも、薬物の有効濃度
を、効率的、経済的に維持することができるようにな
る。Also, as in the drug administration device 1 of the present invention,
When the circulation line 2 is provided and the drug circulates in the circulation line 2, it is possible to continuously administer a fresh drug to the patient. Moreover, the effective concentration of the drug can be maintained efficiently and economically.
【００６６】さらには、図１に示す薬物投与装置１のよ
うに、バイパスライン３を設け、かかるバイパスライン
３の上流端を心筋保護剤供給手段４の上流側、下流端を
心筋保護剤供給手段４の下流側に設置すると、薬物投与
装置１の回路構成を大幅に複雑化しないで、遺伝子治療
薬の温度を調整しつつ遺伝子治療薬を薬物投与装置１内
で循環させることができるようになる。これにより、送
液ポンプ、冷却系を共有するため操作性、信頼性が高く
なる。Further, as in the drug administration device 1 shown in FIG. 1, a bypass line 3 is provided. The upstream end of the bypass line 3 is located on the upstream side of the myocardial protective agent supply means 4 and the downstream end is provided with the myocardial protective agent supply means. 4, the gene therapy drug can be circulated in the drug administration device 1 while adjusting the temperature of the gene therapy drug without significantly complicating the circuit configuration of the drug administration device 1. . Thereby, the operability and reliability are improved because the liquid feed pump and the cooling system are shared.
【００６７】さらには、第１リザーバー４１を設け、か
かる第１リザーバー４１を介して循環ライン２内に心筋
保護剤を供給すると、循環ライン２内の心筋保護剤の循
環量、ひいては、患者への心筋保護剤の投与量の調節が
容易となる。これと同様のことは、第２リザーバー５１
についても言える。Further, when the first reservoir 41 is provided and the myocardial protective agent is supplied into the circulation line 2 via the first reservoir 41, the circulating amount of the myocardial protective agent in the circulation line 2 and, consequently, to the patient It becomes easy to adjust the dose of the cardioprotective agent. The same is true for the second reservoir 51.
Can also be said about.
【００６８】また、薬物投与装置１のように、注入ライ
ン９を循環ライン２に接続し、かかる注入ライン９か
ら、心筋保護剤および遺伝子治療薬を患者に注入するよ
うにすると、患者に接続するチューブ等を削減すること
ができ、治療が行いやすくなる。When the injection line 9 is connected to the circulation line 2 as in the case of the drug administration device 1, the cardioprotective agent and the gene therapy agent are injected from the injection line 9 to the patient. The number of tubes and the like can be reduced, and treatment can be easily performed.
【００６９】このように、薬物投与装置１のような構成
の薬物投与装置を用いて遺伝子治療を行うと、心臓へ薬
液を注入するためのカニュレーションが１箇所で済み、
生体への侵襲が少なくなる。また、本装置のような閉鎖
系に近いシステムを用いることで、薬液が外界に接触
し、汚染されることが防止されるようになる。このため
安全に治療がおこなえる。As described above, when gene therapy is performed using a drug administration device having a configuration such as the drug administration device 1, cannulation for injecting a drug solution into the heart is completed at one place.
Invasion to the living body is reduced. In addition, by using a system close to a closed system such as the present apparatus, the chemical solution is prevented from coming into contact with the outside and being contaminated. Therefore, the treatment can be performed safely.
【００７０】なお、薬物投与装置は、図２に示す薬物投
与装置１’のように、第２リザーバー５１から流出した
遺伝子治療薬が、第２リザーバー５１に再流入しないよ
うな構成としてもよい。The drug administration device may be configured such that the gene therapy drug flowing out of the second reservoir 51 does not flow again into the second reservoir 51, as in the drug administration device 1 'shown in FIG.
【００７１】また、薬物投与装置は、図３に示す薬物投
与装置１”のように、遺伝子治療薬貯留部５３を第１リ
ザーバー４１に接続し、第１リザーバー４１が、心筋保
護剤供給手段４および遺伝子治療薬供給手段５の構成要
素を兼有していてもよい。この場合、図３に示すよう
に、心筋保護剤貯留部４３と第１リザーバー４１との
間、および遺伝子治療薬貯留部５３と第１リザーバー４
１との間にバルブを設置するとよい。In the drug administration device, like the drug administration device 1 ″ shown in FIG. 3, the gene therapy drug reservoir 53 is connected to the first reservoir 41, and the first reservoir 41 is connected to the myocardial protective agent supply means 4. And may also serve as a component of the gene therapy drug supply means 5. In this case, as shown in Fig. 3, between the myocardial protective agent reservoir 43 and the first reservoir 41, and between the gene therapy drug reservoir and the gene therapy drug reservoir. 53 and the first reservoir 4
It is advisable to install a valve between them.
【００７２】なお、以上述べた本発明の実施の形態で
は、心臓の細胞を保護する薬の代表として心筋保護剤を
用いたが、心臓の細胞を保護する薬には、心筋保護剤以
外の他の薬物、例えば、ステロイド、カルシウム拮抗
剤、グルコースとインスリン等を用いてもよく、これら
を心筋保護剤に添加してもよい。また、以上述べた本発
明の実施の形態では、心臓の細胞を治療する薬の代表と
して遺伝子治療薬を用いたが、心臓の細胞を治療する薬
には、遺伝子治療薬以外の他の薬物、例えば、心不全治
療薬、免疫抑制剤等を用いてもよい。In the above-described embodiment of the present invention, a cardioprotective agent is used as a representative of a drug for protecting heart cells. May be used, for example, steroids, calcium antagonists, glucose and insulin, and these may be added to the cardioplegic agent. Further, in the embodiment of the present invention described above, a gene therapy drug was used as a representative of drugs for treating heart cells, but drugs for treating heart cells include drugs other than gene therapy drugs, For example, a therapeutic agent for heart failure, an immunosuppressant, or the like may be used.
【００７３】なお、以上述べた本発明の実施の形態で
は、流路切り換え手段８は、三方活栓で構成したが、流
路切り換え手段８は、液の流路を切り換えることが可能
であれば、三方活栓以外のもので構成してもよいことは
言うまでもない。In the embodiment of the present invention described above, the flow path switching means 8 is constituted by a three-way cock. However, if the flow path switching means 8 can switch the liquid flow path, It goes without saying that the stopcock may be constituted by something other than the three-way cock.
【００７４】以上述べた本発明の実施の形態では、温度
調整手段６は、循環ライン２の下流域２８に設けたが、
例えば、上流域２６に設けてもよい。また、治療に必要
のない場合は、温度調整手段６は、設けなくてもよい。In the embodiment of the present invention described above, the temperature adjusting means 6 is provided in the downstream area 28 of the circulation line 2.
For example, it may be provided in the upstream area 26. If the treatment is not necessary, the temperature adjusting means 6 may not be provided.
【００７５】また、以上述べた本発明の実施の形態で
は、循環ライン２上に第１リザーバー４１を設置し、か
かる第１リザーバー４１を介して、心筋保護剤を循環ラ
イン２内に供給したが、例えば、心筋保護剤貯留部４３
を循環ライン２に直接接続し、心筋保護剤を心筋保護剤
貯留部４３から循環ライン２に直接供給してもよい。同
様に、例えば、遺伝子治療薬貯留部５３をバイパスライ
ン３に直接接続し、遺伝子治療薬を遺伝子治療薬貯留部
５３からバイパスライン３に直接供給してもよい。In the embodiment of the present invention described above, the first reservoir 41 is installed on the circulation line 2, and the myocardial protective agent is supplied into the circulation line 2 via the first reservoir 41. For example, the myocardial protective agent reservoir 43
May be directly connected to the circulation line 2 and the myocardial protective agent may be directly supplied from the myocardial protective agent reservoir 43 to the circulating line 2. Similarly, for example, the gene therapy drug reservoir 53 may be directly connected to the bypass line 3, and the gene therapy drug may be directly supplied from the gene therapy drug reservoir 53 to the bypass line 3.
【００７６】本発明の薬物投与装置１は、遺伝子治療以
外の心臓の治療法に用いてもよい。また、本発明の薬物
投与装置１は、心臓以外の臓器、組織の治療に用いても
よい。さらには、本発明の薬物投与装置１は、治療以外
の目的、例えば、診断、予防、移植等に用いてもよい。The drug administration device 1 of the present invention may be used for a method of treating a heart other than gene therapy. Further, the drug administration device 1 of the present invention may be used for treating organs and tissues other than the heart. Furthermore, the drug administration device 1 of the present invention may be used for purposes other than treatment, such as diagnosis, prevention, and transplantation.
【００７７】以上述べた説明では、第１の薬物として、
心臓の細胞を保護する薬（心筋保護剤）を用いたが、第
１の薬物には、心臓の細胞を保護する薬以外の薬物、例
えば、冷却した生理食塩水、リンゲル液等を用いてもよ
い。また、以上述べた説明では、第２の薬物として、心
臓の細胞を治療する薬（遺伝子治療薬）を用いたが、第
２の薬物には、心臓の細胞を治療する薬以外の薬物を用
いてもよい。In the above description, as the first drug,
Although a drug that protects heart cells (a cardioplegic agent) was used, a drug other than a drug that protects heart cells, such as a cooled saline solution or Ringer's solution, may be used as the first drug. . In the above description, a drug (gene therapy drug) for treating heart cells is used as the second drug, but a drug other than a drug for treating heart cells is used as the second drug. You may.
【００７８】[0078]
【実施例】§１．遺伝子治療薬の調製 心臓における遺伝子治療において、最も基本となる操作
は、遺伝子導入法である。遺伝子導入法としては、リン
酸カルシウム法やＤＥＡＥ（ジエチルアミノエチル）-
デキストラン法などの化学的方法、合成脂質を用いるリ
ポソーム法やエレクトロポレーションなどの物理的方
法、レトロウィルス、アデノウィルス、パラミクソウィ
ルス等のウイルスベクターを用いる方法、これらを折中
した方法などが、挙げられる。Embodiment §1. Preparation of Gene Therapy The most basic operation in gene therapy in the heart is gene transfer. Gene transfer methods include the calcium phosphate method and DEAE (diethylaminoethyl)-
Chemical methods such as the dextran method, physical methods such as the liposome method and electroporation using synthetic lipids, methods using viral vectors such as retroviruses, adenoviruses, and paramyxoviruses, and methods involving these methods are listed. Can be
【００７９】これらはそれぞれ、効率や安全性の点で一
長一短を有するが、本実施例では、リポソーム法とウイ
ルスベクターを用いる方法とを折中し両者の利点が得ら
れる、ＨＶＪ−リポソーム法を用いた。ＨＶＪ−リポソ
ーム法は、高い安全性と高い発現高率とを有している。
なお、本発明では、遺伝子導入法は、遺伝子治療薬へ遺
伝子を導入できれば、ＨＶＪ−リポソーム法にこだわら
ない。Each of these methods has advantages and disadvantages in terms of efficiency and safety. In this example, however, the HVJ-liposome method is used, in which the liposome method and the method using a virus vector can be used to obtain both advantages. Was. The HVJ-liposome method has high safety and high expression rate.
In the present invention, the gene introduction method is not limited to the HVJ-liposome method as long as the gene can be introduced into a gene therapy drug.
【００８０】まず、フォスファチヂルコリン１３０μ
Ｌ、ＤＯＰＥ１２．２５mg、スフィンゴミエリン１１．
７５mg、コレステロール２４mgを量り取り、これらを、
３．５mLのクロロホルムに溶解させた。これとは別に、
フォスファチヂルセリン１０mgを、０．５mLのクロロホ
ルムに溶解させた。次に、これら２液を混ぜ合わせ、得
られた溶液を、チューブに０．５mLずつ分注した。次
に、チューブ内の空気を窒素ガスで置換して、このチュ
ーブを氷上で冷やした。次に、このチューブ内の溶液
を、ロータリーエバポレーターで乾固させた。次に、こ
のチューブを、酸化防止のため窒素ガスで封入し、−２
０℃に冷却、保存した。First, phosphatidylcholine 130 μm
L, DOPE 12.25 mg, sphingomyelin 11.
Weigh 75 mg, cholesterol 24 mg,
Dissolved in 3.5 mL of chloroform. Aside from this,
10 mg of phosphatidylserine was dissolved in 0.5 mL of chloroform. Next, these two solutions were mixed, and the resulting solution was dispensed into tubes in a volume of 0.5 mL. Next, the air in the tube was replaced with nitrogen gas, and the tube was cooled on ice. Next, the solution in the tube was dried using a rotary evaporator. Next, the tube was sealed with nitrogen gas to prevent oxidation.
Cooled to 0 ° C and stored.
【００８１】次に、このチューブに、β−ガラクトシダ
ーゼ遺伝子を持つ発現プラスミドを１mg/mL含有する溶
液を、２００μＬ加えた。その後ただちに、チューブを
ボルテックスミキサーで３０秒間激しく振盪し、次い
で、３７℃の恒温槽に３０秒間静置する操作を、８回繰
り返した。次に、水をはった超音波発生装置にチューブ
を入れ、５秒間超音波処理をし、その後、再度３０秒間
ボルテックスミキサーでチューブを振盪した。Next, 200 μL of a solution containing 1 mg / mL of an expression plasmid having a β-galactosidase gene was added to this tube. Immediately thereafter, the operation of vigorously shaking the tube with a vortex mixer for 30 seconds, and then leaving the tube to stand in a thermostat at 37 ° C. for 30 seconds was repeated eight times. Next, the tube was put into an ultrasonic generator filled with water, subjected to ultrasonic treatment for 5 seconds, and then shaken again with a vortex mixer for 30 seconds.
【００８２】次に、このチューブに０．３mLのＢＳＳを
加え、３７℃の振盪恒温槽でチューブを、１００〜１２
０回／分で３０分間振盪した。Next, 0.3 mL of BSS was added to the tube, and the tube was placed in a shaking constant temperature bath at 37 ° C. for 100 to 12 hours.
Shake at 0 times / min for 30 minutes.
【００８３】次に、このチューブに不活性化したＨＶＪ
を１０，０００〜３０，０００ＨＡＵ加え、次いで、こ
のチューブを氷上に１０分間置いた。次に、このチュー
ブを３７℃の振盪恒温槽に斜めに差し込み、このチュー
ブを、１００〜１２０回／分で３０分間振盪した。これ
により、ＨＶＪ−リポソームが生成された。Next, the inactivated HVJ was added to this tube.
Was added to 10,000 to 30,000 HAU, and the tubes were then placed on ice for 10 minutes. Next, this tube was obliquely inserted into a shaking thermostat at 37 ° C., and the tube was shaken at 100 to 120 times / min for 30 minutes. This produced HVJ-liposomes.
【００８４】次に、１０mLの超遠心チューブに、３０％
ショ糖溶液を７mL加え、この上にＨＶＪ−リポソーム液
を静かにのせ、次いで、ＢＳＳを超遠心チューブの口付
近まで加えた。次に、この超遠心チューブを、スイング
型ロータの超遠心機で、６２，８００ｇ、４℃で、２時
間超遠心した。遠心後、３０％ショ糖溶液層のすぐ上に
白色の粒子として集積したＨＶＪ−リポソームを、パス
ツールピペットで回収した。これにより、精製されたＨ
ＶＪ−リポソーム液が得られた。このＨＶＪ−リポソー
ム液を、使用時まで４℃で保存し、その後以下に示す遺
伝子治療に用いた。Next, 30% was added to a 10 mL ultracentrifuge tube.
7 mL of a sucrose solution was added, and the HVJ-liposome solution was gently put on the sucrose solution. Then, BSS was added to the vicinity of the mouth of the ultracentrifuge tube. Next, this ultracentrifuge tube was ultracentrifuged at 62,800 g and 4 ° C. for 2 hours using a swing type rotor ultracentrifuge. After centrifugation, HVJ-liposomes accumulated as white particles immediately above the 30% sucrose solution layer were collected with a Pasteur pipette. Thereby, the purified H
A VJ-liposome solution was obtained. This HVJ-liposome solution was stored at 4 ° C. until use, and then used for the following gene therapy.
【００８５】§２．遺伝子治療薬の投与 まず、図１に示すような薬物投与装置１を組み立てた。
なお、心筋保護剤貯留部４３の容量は２０００mL、遺伝
子治療薬貯留部５３の容量は２０００mL、第１リザーバ
ー４１の容量は５０００mL、第２リザーバー５１の容量
は５０００mLとした。また、薬物投与装置１から実験動
物の心臓に薬物を注入するための注入カニューレ、およ
び、心臓に注入した薬物を排出するためのベントカニュ
ーレを用意した。心筋保護剤としては、細胞外液タイプ
ではSt.Thomas液等、細胞内液タイプでは、Bretschneid
er液等があるが、本実施例では、セント・トーマス第２
液（自家製）を心筋保護剤として用い、これを薬物投与
装置１の心筋保護剤貯留部４３に１０００mL貯留した。
また、遺伝子治療薬貯留部５３に、上記§１．で調製し
たＨＶＪ−リポソーム液を２００mL貯留した。§2. Administration of Gene Therapy First, a drug administration device 1 as shown in FIG. 1 was assembled.
The capacity of the myocardial protective agent storage section 43 was 2000 mL, the capacity of the gene therapy drug storage section 53 was 2000 mL, the capacity of the first reservoir 41 was 5000 mL, and the capacity of the second reservoir 51 was 5000 mL. Further, an injection cannula for injecting the drug from the drug administration device 1 into the heart of the experimental animal and a vent cannula for discharging the drug injected into the heart were prepared. As a myocardial protective agent, St. Thomas solution etc. for extracellular fluid type, Bretschneid for intracellular fluid type
er liquid, etc., but in this embodiment, St. Thomas second
The liquid (made in-house) was used as a myocardial protective agent, and 1000 mL of this was stored in the myocardial protective agent storage section 43 of the drug administration device 1.
In addition, the gene therapy drug storage unit 53 stores the above §1. 200 mL of the HVJ-liposome solution prepared in the above was stored.
【００８６】次に、薬物投与装置１の各ライン（循環ラ
イン２、バイパスライン３、注入ライン９およびベント
ライン１００）内を生理食塩水で洗浄した。なお、洗浄
後、この液は捨てた。次に、生理食塩水を２０００mL用
い、薬物投与装置１のプライミングを行った。Next, the inside of each line (circulation line 2, bypass line 3, injection line 9 and vent line 100) of the drug administration device 1 was washed with physiological saline. After washing, this solution was discarded. Next, priming of the drug administration device 1 was performed using 2000 mL of physiological saline.
【００８７】その後、適当な時期に、心筋保護剤を心筋
保護剤貯留部４３から第１リザーバー４１に供給し、灌
流を開始し、心筋保護剤を循環ライン２内で循環させ
た。なお、温度調整手段６では、熱交換器６１の温度
（心筋保護剤および遺伝子治療薬の温度）を４℃に設定
した。Thereafter, at an appropriate time, the myocardial protective agent was supplied from the myocardial protective agent storage section 43 to the first reservoir 41 to start perfusion, and the myocardial protective agent was circulated in the circulation line 2. In the temperature adjusting means 6, the temperature of the heat exchanger 61 (the temperature of the cardioplegic agent and the gene therapy drug) was set to 4 ° C.
【００８８】これとは別に、常法に従い、人工肺（テル
モ社製「キャピオックス」）、カーディオトミー・リザ
ーバー、動脈ポンプ、吸引ポンプ、電気温度計等を用い
て人工心肺装置を組み立てた。また、この人工心肺装置
に接続する送血カニューレおよび脱血カニュ−レを用意
した。Separately, an artificial heart-lung machine was assembled according to a conventional method using an artificial lung (“Capiox” manufactured by Terumo Corporation), a cardiotomy reservoir, an arterial pump, a suction pump, an electric thermometer, and the like. In addition, a blood feeding cannula and a blood removal cannula to be connected to the heart-lung machine were prepared.
【００８９】次に、カーディオトミー・リザーバーから
ヘパリン加５％ブドウ糖液および滅菌蒸留水を、５００
〜１０００Ｌ注入して、人工心肺装置内の回路を洗浄し
た。なお、洗浄後、これらの液はすべて捨てた。その
後、ヘパリン加乳酸リンゲル液を用い、人工心肺装置の
プライミングを開始した。Next, 5% heparinized glucose solution and sterilized distilled water were added from a cardiotomy reservoir to 500 ml.
The circuit in the heart-lung machine was washed by injecting １０００1000 L. After washing, all of these liquids were discarded. Thereafter, priming of the heart-lung machine was started using heparinized lactated Ringer's solution.
【００９０】人工心肺装置のプライミングと平行して、
ビーグル犬（２才、メス、１８kg、チャールズリバー）
に麻酔を施し、次いで、このビーグル犬に対して左第４
〜６肋間後方開胸（注：左胸壁の側面から背方にかけて
横切開する術式）を行った。次に、ヘパリンを、２mg/k
g、心臓内に注入した。In parallel with the priming of the heart-lung machine,
Beagle dog (2 years old, female, 18kg, Charles River)
Anesthetized, and then left the fourth
-6 intercostal posterior thoracotomy (Note: a technique of transection incision from the side of the left chest wall to the back) was performed. Next, heparin was added at 2 mg / k
g, injected into the heart.
【００９１】次に、大腿部を切開し、大腿動脈を露出さ
せた。次に、大腿動脈の末梢側を血管鉗子で挟み、次い
で、動脈壁を切開し、その後、送血カニューレを大腿動
脈内に４〜５cm挿入し、送血カニューレを固定した。次
に、脱血カニューレを右心房から上下大静脈へ挿入し、
固定した。送血カニューレおよび脱血カニュ−レを挿入
後、送血回路内に空気が入らないように、これら送血カ
ニューレおよび脱血カニュ−レを、人工心肺装置の主回
路に接続した。Next, the thigh was incised to expose the femoral artery. Next, the distal side of the femoral artery was pinched with vascular forceps, and then the arterial wall was incised. Thereafter, a blood-feeding cannula was inserted 4 to 5 cm into the femoral artery to fix the blood-feeding cannula. Next, insert a blood removal cannula from the right atrium into the upper and lower vena cava,
Fixed. After inserting the blood supply cannula and the blood removal cannula, the blood supply cannula and the blood removal cannula were connected to the main circuit of the heart-lung machine to prevent air from entering the blood supply circuit.
【００９２】次に、人工心肺装置の静脈回路を開き、ポ
ンプをゆっくり回転させ、脱血量（静脈血流量）を除々
に増加させ、それに合わせて送血量（動脈血流量）を増
加させ、順次、上下大静脈および上行大動脈を遮断し
た。次に、前述した薬物注入用の注入カニューレを、上
行大動脈に挿入した。そして、この注入カニューレを、
薬液投与装置１の注入ライン９に接続した。また、ベン
トカニューレを肺動脈に挿入し、このベントカニューレ
を、薬物投与装置１のベントライン１００に接続した。Next, the venous circuit of the heart-lung machine was opened, the pump was slowly rotated to gradually increase the blood removal volume (venous blood flow volume), and the blood transmission volume (arterial blood flow volume) accordingly. The upper and lower vena cava and ascending aorta were blocked. Next, the injection cannula for drug injection described above was inserted into the ascending aorta. And this infusion cannula,
It was connected to the injection line 9 of the drug solution administration device 1. Further, a vent cannula was inserted into the pulmonary artery, and this vent cannula was connected to the vent line 100 of the drug administration device 1.
【００９３】次に、切り換えバルブ７を操作し、循環ラ
イン２内を循環させていた心筋保護液を、間欠的灌流方
法で、注入ライン９から、注入カニューレ、上行大動脈
を経て左心室内に注入し、心停止させた。Next, the switching valve 7 is operated to inject the cardioplegic solution circulated in the circulation line 2 from the injection line 9 into the left ventricle via the injection cannula and the ascending aorta by the intermittent perfusion method. And arrested.
【００９４】次に、遺伝子治療薬貯留部５３から第２リ
ザーバー５１に、ＨＶＪ−リポソーム液（遺伝子治療
薬）を供給した。次に、切り換えバルブ７、第１三方活
栓８１および第２三方活栓８２を操作することにより、
バイパスライン３すなわち遺伝子治療薬供給手段５への
流路を開放し、中流域２７すなわち心筋保護剤供給手段
４への流路を遮蔽し、ＨＶＪ−リポソーム液を、バイパ
スライン３、下流域２８および上流域２６で、循環させ
た。Next, the HVJ-liposome solution (gene therapeutic agent) was supplied from the gene therapeutic drug reservoir 53 to the second reservoir 51. Next, by operating the switching valve 7, the first three-way cock 81 and the second three-way cock 82,
The bypass line 3, that is, the flow path to the gene therapy drug supply means 5 is opened, the middle flow area 27, that is, the flow path to the myocardial protective agent supply means 4, is blocked, and the HVJ-liposome solution is supplied to the bypass line 3, the downstream area 28, In the upstream area 26, circulation was carried out.
【００９５】次に、切り換えバルブ７を操作し、ＨＶＪ
−リポソーム液を、注入ライン９から、注入カニュー
レ、上行大動脈を経て左心室内に注入した。Next, the switching valve 7 is operated and the HVJ
-The liposome solution was injected into the left ventricle from the injection line 9 via the injection cannula and the ascending aorta.
【００９６】ＨＶＪ−リポソーム液を１０分間心臓内に
滞留させた後、切り換えバルブ７を操作し、肺動脈に挿
入したベントライン１００から循環ライン２（上流域２
６、バイパスライン３、下流域２８）および注入ライン
９を通し、ＨＶＪ−リポソームを、心臓と薬物投与装置
１との間で循環させた。この時、新たに遺伝子治療薬貯
留部５３からＨＶＪ−リポソーム液を同量、第２リザー
バー５１に加え薬液の有効濃度を維持した。３０分後、
切り換えバルブ７、第１三方活栓８１および第２三方活
栓８２を操作し、新たな心筋保護液を、注入ライン９か
ら、注入カニューレ、上行大動脈を経て左心室内に注入
した。これにより、左心室内の薬物がＨＶＪ−リポソー
ム液から心筋保護剤に置換され、心臓内に注入したＨＶ
Ｊ−リポソーム液の大部分は、ベントカニューレから排
出された。このため、体内に残留したＨＶＪ−リポソー
ム（遺伝子治療薬）は、極めて少量であったと思われ
る。After the HVJ-liposome solution was allowed to stay in the heart for 10 minutes, the switching valve 7 was operated, and the circulation line 2 (upstream region 2) was inserted from the vent line 100 inserted into the pulmonary artery.
HVJ-liposome was circulated between the heart and the drug administration device 1 through 6, bypass line 3, downstream zone 28) and injection line 9. At this time, the same amount of HVJ-liposome solution was newly added from the gene therapy drug reservoir 53 to the second reservoir 51 to maintain the effective concentration of the drug solution. 30 minutes later,
By operating the switching valve 7, the first three-way cock 81 and the second three-way cock 82, a new myocardial protective solution was injected from the injection line 9 into the left ventricle via the injection cannula and the ascending aorta. As a result, the drug in the left ventricle is replaced from the HVJ-liposome solution by the myocardial protective agent, and the HV injected into the heart.
Most of the J-liposome solution was drained from the vent cannula. Therefore, it is considered that the amount of HVJ-liposome (gene therapeutic agent) remaining in the body was extremely small.
【００９７】次に、注入カニューレの抜去を行い、加温
を開始後、上行大動脈の遮断を解除した。その後、心臓
の鼓動は再開した。これとともに、静脈の遮断紐を緩
め、部分体外循環とし、心臓内の空気を抜きながら、心
臓創を縫合閉鎖した。次いで、左心系の空気を完全に除
きながら、ベントカニューレを抜去した。Next, the injection cannula was removed, and after heating was started, the ascending aorta was released from the block. Thereafter, the heartbeat resumed. At the same time, the lace of the vein was loosened to achieve partial extracorporeal circulation, and the heart wound was closed with suture while evacuating the heart. The vent cannula was then withdrawn while completely removing the left ventricular air.
【００９８】最後に、大動脈起始部に開けた空気ベント
孔を閉鎖し、人工心肺の回転を次第に少なくし、回転を
止めた。人工心肺の回転が止まってから、脱血カニュー
レおよび送血カニューレを抜去した。そして、心膜を縫
合し、肋骨を閉胸した。さらには、筋肉及び皮下組織を
縫合して、最後に皮膚を縫合し、心臓に対する遺伝子治
療を終了した。Finally, the air vent hole opened at the origin of the aorta was closed, and the rotation of the heart-lung machine was gradually reduced and stopped. After the cardiopulmonary bypass stopped rotating, the blood removal cannula and blood transfusion cannula were removed. The pericardium was sutured and the ribs closed. Furthermore, the muscle and subcutaneous tissue were sutured, and finally the skin was sutured, and the gene therapy for the heart was completed.
【００９９】手術後、経過は良好であり、数ヶ月経過し
ても、ビーグル犬には、遺伝子治療薬の副作用、手術の
後遺症等は、特に確認されなかった。After the operation, the course was good. Even after several months, no side effects of the gene therapy drug, no sequelae of the operation, etc. were confirmed in the beagle dog.
【０１００】[0100]
【発明の効果】以上述べたように、本発明によれば、薬
物を好適に生体内に投与することができる。特に、本発
明の薬物投与装置を心臓疾患の治療に用いれば、心臓に
局所的に投薬を行うことができ、心臓以外の組織、臓器
等に影響を与えにくくなる。このため、本発明の薬物投
与装置を用いて心臓に対して遺伝子治療を行えば、心臓
の細胞に選択的に遺伝子を導入することが可能である。
したがって、本発明によれば、心臓病の治療、心保存や
心筋保護、心臓移植における拒絶反応などの諸問題に対
し、遺伝子治療等の新たな治療法を、積極的かつ好適に
展開することが可能となる。As described above, according to the present invention, a drug can be suitably administered to a living body. In particular, when the drug administration device of the present invention is used for treating a heart disease, medication can be locally applied to the heart, and tissues and organs other than the heart are less likely to be affected. Therefore, if gene therapy is performed on the heart using the drug administration device of the present invention, it is possible to selectively introduce a gene into cells of the heart.
Therefore, according to the present invention, it is possible to aggressively and suitably develop new therapeutic methods such as gene therapy for various problems such as treatment of heart disease, cardiac preservation and protection of myocardium, and rejection in heart transplantation. It becomes possible.
【図１】本発明の薬物投与装置の実施形態を示す回路図
である。FIG. 1 is a circuit diagram showing an embodiment of a drug administration device of the present invention.
【図２】本発明の薬物投与装置の他の実施形態を示す回
路図である。FIG. 2 is a circuit diagram showing another embodiment of the drug administration device of the present invention.
【図３】本発明の薬物投与装置の他の実施形態を示す回
路図である。FIG. 3 is a circuit diagram showing another embodiment of the drug administration device of the present invention.
１、１’、１” 薬物投与装置 ２ 循環ライン ２１ ポンプ ２６ 上流域 ２７ 中流域 ２８ 下流域 ３ バイパスライン ３６ 上流 ３７ 下流 ４ 心筋保護剤供給手段 ４１ 第１リザーバー ４３ 心筋保護剤貯留部 ５ 遺伝子治療薬供給手段 ５１ 第２リザーバー ５３ 遺伝子治療薬貯留部 ６ 温度調整手段 ６１ 熱交換器 ６２ 熱交換ライン ６３ 温度調整機 ７ 切り換えバルブ ８ 流路切り換え手段 ８１ 第１三方活栓 ８１１ ポート ８２ 第２三方活栓 ８２１ ポート ９ 注入ライン １００ ベントライン 1, 1 ', 1 "Drug administration device 2 Circulation line 21 Pump 26 Upstream area 27 Midstream area 28 Downstream area 3 Bypass line 36 Upstream 37 Downstream 4 Cardioplegic agent supply means 41 First reservoir 43 Cardioplegic agent reservoir 5 Gene therapy Drug supply means 51 Second reservoir 53 Gene therapy drug storage section 6 Temperature adjustment means 61 Heat exchanger 62 Heat exchange line 63 Temperature regulator 7 Switching valve 8 Flow path switching means 81 First three-way cock 811 port 82 Second three-way cock 821 Port 9 injection line 100 vent line
───────────────────────────────────────────────────── フロントページの続き (72)発明者 金田 安史 大阪府箕面市小野原東６−12−８ Ｆターム(参考） 4C066 AA01 BB01 CC01 DD11 EE13 FF01 HH30 LL03 ────────────────────────────────────────────────── ─── Continued on the front page (72) Inventor Yasushi Kaneda 6-12-8 Onoharahigashi, Minoh-shi, Osaka F-term (reference) 4C066 AA01 BB01 CC01 DD11 EE13 FF01 HH30 LL03
Claims (17)
あって、 薬物を循環させる循環ラインと、 第１の薬物を前記循環ラインに供給する第１の薬物供給
手段と、 第２の薬物を前記循環ラインに供給する第２の薬物供給
手段とを有することを特徴とする薬物投与装置。1. A drug administration device for administering a drug into a living body, comprising: a circulating line for circulating the drug; first drug supply means for supplying a first drug to the circulating line; And a second drug supply means for supplying the drug to the circulation line.
インの流路の途中に設置されたリザーバーと、該リザー
バーに接続され、前記第１の薬物を貯留する貯留部とを
有する請求項１に記載の薬物投与装置。2. The method according to claim 1, wherein the first drug supply unit includes a reservoir installed in the flow path of the circulation line, and a storage unit connected to the reservoir and storing the first drug. 2. The drug administration device according to 1.
インを有し、 前記第２の薬物供給手段は、前記バイパスライン上に設
けられている請求項１または２に記載の薬物投与装置。3. The drug administration device according to claim 1, further comprising a bypass line branched from the circulation line, wherein the second drug supply unit is provided on the bypass line.
と、該リザーバーに接続され、前記第２の薬物を貯留す
る貯留部とを有する請求項１ないし３のいずれかに記載
の薬物投与装置。4. The drug administration device according to claim 1, wherein the second drug supply unit has a reservoir and a storage unit connected to the reservoir and storing the second drug. .
インを有し、 前記リザーバーは、前記バイパスラインの流路の途中に
設置されている請求項４に記載の薬物投与装置。5. The drug administration device according to claim 4, further comprising a bypass line branching from the circulation line, wherein the reservoir is provided in a middle of a flow path of the bypass line.
第２の薬物供給手段への流路とを切り換える流路切り換
え手段を有する請求項１ないし５のいずれかに記載の薬
物投与装置。6. The drug administration according to claim 1, further comprising a flow path switching means for switching a flow path to said first drug supply means and a flow path to said second drug supply means. apparatus.
温度を調整する温度調整手段を有する請求項１ないし６
のいずれかに記載の薬物投与装置。7. A temperature adjusting means for adjusting the temperature of the first and / or second drug.
The drug administration device according to any one of the above.
給手段および前記第２の薬物供給手段よりも下流側の前
記循環ライン上に設けられている請求項７に記載の薬物
投与装置。8. The drug administration device according to claim 7, wherein the temperature adjustment unit is provided on the circulation line downstream of the first drug supply unit and the second drug supply unit.
を有する請求項１ないし８のいずれかに記載の薬物投与
装置。9. The drug administration device according to claim 1, further comprising an injection line for injecting the drug into a living body.
後、前記第２の薬物を生体内に投与する請求項１ないし
９のいずれかに記載の薬物投与装置。10. The drug administration device according to claim 1, wherein after administering the first drug into a living body, the second drug is administered into a living body.
薬効を助長、および／または、前記第２の薬物の副作用
を抑制する請求項１ないし１０のいずれかに記載の薬物
投与装置。11. The drug administration device according to claim 1, wherein the first drug promotes the efficacy of the second drug and / or suppresses a side effect of the second drug. .
する薬である請求項１ないし１１のいずれかに記載の薬
物投与装置。12. The drug administration device according to claim 1, wherein the first drug is a drug that protects cells of the heart.
請求項１ないし１２のいずれかに記載の薬物投与装置。13. The drug administration device according to claim 1, wherein the first drug is a cardioprotective drug.
する薬である請求項１ないし１３のいずれかに記載の薬
物投与装置。14. The drug administration device according to claim 1, wherein the second drug is a drug for treating cells of the heart.
る請求項１ないし１４のいずれかに記載の薬物投与装
置。15. The drug administration device according to claim 1, wherein the second drug is a gene therapy drug.
有し、 該注入ラインを介して心臓を停止させるための薬物を生
体内に注入し、次いで、遺伝子治療薬を生体内に注入す
るように構成されたことを特徴とする薬物投与装置。16. An injection line for injecting a drug into a living body, wherein a drug for stopping a heart is injected into the living body via the injection line, and then a gene therapy drug is injected into the living body. A drug administration device characterized in that:
有し、 この温度調整手段を用いて前記心臓を停止させるための
薬物または前記遺伝子治療薬の少なくとも一方の温度を
調整して、前記心臓を停止させるための薬物および前記
遺伝子治療薬を生体内に注入することができる請求項１
６に記載の薬物投与装置。17. A method for adjusting the temperature of at least one of a drug for stopping the heart or the gene therapy drug by using the temperature adjusting means for adjusting a temperature of a drug. 2. A drug for stopping the disease and the gene therapy drug can be injected into a living body.
7. The drug administration device according to 6.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000070089A JP2001252354A (en) | 2000-03-14 | 2000-03-14 | Dosing device |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000070089A JP2001252354A (en) | 2000-03-14 | 2000-03-14 | Dosing device |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2001252354A true JP2001252354A (en) | 2001-09-18 |
Family
ID=18588875
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000070089A Pending JP2001252354A (en) | 2000-03-14 | 2000-03-14 | Dosing device |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2001252354A (en) |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2018062486A (en) * | 2016-10-14 | 2018-04-19 | 株式会社 バイオミメティクスシンパシーズ | Stem cells and administration system |
| CN109872792A (en) * | 2019-04-16 | 2019-06-11 | 北京中佰耀因医药科技有限公司 | It is a kind of for instructing the genetic test intelligent reporting system of accurate medication |
| CN109979545A (en) * | 2019-04-16 | 2019-07-05 | 北京中佰耀因医药科技有限公司 | A kind of accurate medication intelligent reporting system of the module of state information management containing sample |
| CN109994176A (en) * | 2019-04-16 | 2019-07-09 | 北京中佰耀因医药科技有限公司 | A kind of accurate medication intelligent reporting system of the information management module containing sample type |
| CN109994156A (en) * | 2019-04-16 | 2019-07-09 | 北京中佰耀因医药科技有限公司 | A kind of accurate medication intelligent reporting system of the information management module containing report template |
| CN109994180A (en) * | 2019-04-16 | 2019-07-09 | 北京中佰耀因医药科技有限公司 | A kind of accurate medication intelligent reporting system of the information management module containing gene loci |
| CN110010220A (en) * | 2019-04-16 | 2019-07-12 | 北京中佰耀因医药科技有限公司 | A kind of method that Semi-Automatic Generation is used to that the genetic test of accurate medication to be instructed to report |
| CN110021442A (en) * | 2019-04-16 | 2019-07-16 | 北京中佰耀因医药科技有限公司 | A kind of accurate medication intelligent reporting system of the information management module of library containing knowledge on drug abuse |
| CN110033841A (en) * | 2019-04-16 | 2019-07-19 | 北京中佰耀因医药科技有限公司 | A method of it generates for instructing the genetic test of accurate medication to report |
| CN110033839A (en) * | 2019-04-16 | 2019-07-19 | 北京中佰耀因医药科技有限公司 | A method of it is automatically generated for instructing the genetic test of accurate medication to report |
| CN110033842A (en) * | 2019-04-16 | 2019-07-19 | 北京中佰耀因医药科技有限公司 | A kind of accurate medication intelligent reporting system of the information management module containing data dictionary |
-
2000
- 2000-03-14 JP JP2000070089A patent/JP2001252354A/en active Pending
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2018062486A (en) * | 2016-10-14 | 2018-04-19 | 株式会社 バイオミメティクスシンパシーズ | Stem cells and administration system |
| CN109872792A (en) * | 2019-04-16 | 2019-06-11 | 北京中佰耀因医药科技有限公司 | It is a kind of for instructing the genetic test intelligent reporting system of accurate medication |
| CN109979545A (en) * | 2019-04-16 | 2019-07-05 | 北京中佰耀因医药科技有限公司 | A kind of accurate medication intelligent reporting system of the module of state information management containing sample |
| CN109994176A (en) * | 2019-04-16 | 2019-07-09 | 北京中佰耀因医药科技有限公司 | A kind of accurate medication intelligent reporting system of the information management module containing sample type |
| CN109994156A (en) * | 2019-04-16 | 2019-07-09 | 北京中佰耀因医药科技有限公司 | A kind of accurate medication intelligent reporting system of the information management module containing report template |
| CN109994180A (en) * | 2019-04-16 | 2019-07-09 | 北京中佰耀因医药科技有限公司 | A kind of accurate medication intelligent reporting system of the information management module containing gene loci |
| CN110010220A (en) * | 2019-04-16 | 2019-07-12 | 北京中佰耀因医药科技有限公司 | A kind of method that Semi-Automatic Generation is used to that the genetic test of accurate medication to be instructed to report |
| CN110021442A (en) * | 2019-04-16 | 2019-07-16 | 北京中佰耀因医药科技有限公司 | A kind of accurate medication intelligent reporting system of the information management module of library containing knowledge on drug abuse |
| CN110033841A (en) * | 2019-04-16 | 2019-07-19 | 北京中佰耀因医药科技有限公司 | A method of it generates for instructing the genetic test of accurate medication to report |
| CN110033839A (en) * | 2019-04-16 | 2019-07-19 | 北京中佰耀因医药科技有限公司 | A method of it is automatically generated for instructing the genetic test of accurate medication to report |
| CN110033842A (en) * | 2019-04-16 | 2019-07-19 | 北京中佰耀因医药科技有限公司 | A kind of accurate medication intelligent reporting system of the information management module containing data dictionary |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Litwak et al. | Use of a left heart assist device after intracardiac surgery: technique and clinical experience | |
| US5678570A (en) | Method of treating cardiac arrest | |
| JP2002515301A (en) | Pulmonary and systemic blood flow support devices and methods for cardiac surgical procedures | |
| JP2001513495A (en) | Compositions, devices and methods that facilitate surgical procedures | |
| JP2001516768A (en) | Compositions, methods and devices for maintaining organs | |
| WO2012154220A2 (en) | Method of resuscitation | |
| JP2001252354A (en) | Dosing device | |
| Bridges et al. | Global cardiac-specific transgene expression using cardiopulmonary bypass with cardiac isolation | |
| JP4299967B2 (en) | Intratubal administration of the composition to the extravascular tissue of a mammal | |
| US12408993B2 (en) | Systems, devices and methods for resuscitation | |
| Tchouta et al. | Twenty-four-hour normothermic perfusion of isolated ex vivo hearts using plasma exchange | |
| RADOVANCEVIC et al. | Implantation Technique for the HeartMateR Left Ventricular Assist Device | |
| O'Neill Jr et al. | Successful management of right ventricular failure with the ventricular assist pump following aortic valve replacement and coronary bypass grafting | |
| Pla et al. | Ex vivo delivery of viral vectors by organ perfusion for cardiac transplantation gene therapy | |
| Koffsky et al. | A simple left heart assist device for use after intracardiac surgery: development, deployment and clinical experience | |
| US20170143891A1 (en) | Systems and methods for pressure-regulated volume control during cardiopulmonary bypass and perfusion procedures | |
| McSparren et al. | Cardiopulmonary Considerations for Cardiac Surgery in Low and Middle Income Countries | |
| US20140142548A1 (en) | Systems, devices and methods for resuscitation | |
| Yokota et al. | Life-threatening hypoxemic respiratory failure after repair of acute type a aortic dissection: successful treatment with venoarterial extracorporeal life support using a prosthetic graft attached to the right axillary artery | |
| Seifert | Advances in myocardial protection | |
| Cribben et al. | Cardiopulmonary bypass | |
| Cribben et al. | Cardiopulmonary bypass | |
| Kahan | Weaning from Cardiopulmonary Bypass and Management of Difficulties | |
| Kajee | Cardiopulmonary Bypass for the Anaesthetist | |
| Polycarpou et al. | Cardiopulmonary Bypass and Cardioplegia |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20060316 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20080716 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20080722 |
|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080919 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20090310 |