WO2022037599A9 - 二氢卟吩衍生物或其可药用盐、其制备方法、用途、及其与超声医疗系统的组合 - Google Patents
二氢卟吩衍生物或其可药用盐、其制备方法、用途、及其与超声医疗系统的组合 Download PDFInfo
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- WO2022037599A9 WO2022037599A9 PCT/CN2021/113191 CN2021113191W WO2022037599A9 WO 2022037599 A9 WO2022037599 A9 WO 2022037599A9 CN 2021113191 W CN2021113191 W CN 2021113191W WO 2022037599 A9 WO2022037599 A9 WO 2022037599A9
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- Prior art keywords
- compound
- transducer
- pharmaceutically acceptable
- acceptable salt
- ultrasonic
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- A61B17/225—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for for extracorporeal shock wave lithotripsy [ESWL], e.g. by using ultrasonic waves
- A61B17/2251—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for for extracorporeal shock wave lithotripsy [ESWL], e.g. by using ultrasonic waves characterised by coupling elements between the apparatus, e.g. shock wave apparatus or locating means, and the patient, e.g. details of bags, pressure control of bag on patient
- A61B2017/2253—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for for extracorporeal shock wave lithotripsy [ESWL], e.g. by using ultrasonic waves characterised by coupling elements between the apparatus, e.g. shock wave apparatus or locating means, and the patient, e.g. details of bags, pressure control of bag on patient using a coupling gel or liquid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N7/00—Ultrasound therapy
- A61N2007/0004—Applications of ultrasound therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N7/00—Ultrasound therapy
- A61N2007/0086—Beam steering
- A61N2007/0091—Beam steering with moving parts, e.g. transducers, lenses, reflectors
Abstract
Description
Claims (18)
- 一种二氢卟吩衍生物或其可药用盐,具有下式(I)所示的结构:其中,R 1为:其中R 9、R 10、R 11、R 12和R 13可以相同或者不同,并且各自独立地选自C 1-C 6烷基,并且在R 2为C 1-C 6烷氧基或-OH时,R 3和R 4中的一个为以下任一基团:其中R 9、R 10、R 11、R 12和R 13如上定义,并且R 3和R 4中的另一个为C 1-C 6烷氧基或-OH;M为2H或者金属离子,例如二价金属离子如Cu 2+、Fe 2+、Zn 2+、Mg 2+、Ni 2+、Co 2+、Pt 2+、Pd 2+、或者四价金属离子如Sn 4+或Ti 4+。
- 一种制备权利要求1-3中任一项所述的二氢卟吩衍生物或其可药用盐的方法,其中,所述方法包括:a 1:使化合物1即二氢卟吩e6与醇发生酯化反应,得到化合物2:b 1:在缩合剂的作用下,使化合物2与β-丙氨酸叔丁酯盐酸盐发生缩合反应,得到化合物3:d 1:化合物4发生水解反应,得到化合物5:e 1:在缩合剂的作用下,化合物5与氨基酸酯盐酸盐发生缩合反应,得到式II(a)化合物:其中M为2H,或者在与金属氯化物或乙酸根络合物发生反应后而成为金属离子,例如二价金属离子如Cu 2+、Fe 2+、Zn 2+、Mg 2+、Ni 2+、Co 2+、Pt 2+、Pd 2+、或者四价金属离子如Sn 4+或Ti 4+,其中R 8如权利要求1所定义;可选地,在碱性条件下,使式II(a)化合物发生水解反应,生成相应的盐,即式II(b)化合物;或a 2:在碱性条件下,使化合物1即二氢卟吩e6与卤代烷反应,得到化合物10:其中M为2H,或者在与金属氯化物或乙酸根络合物发生反应后而成为金属离子,例如二价金属离子如Cu 2+、Fe 2+、Zn 2+、Mg 2+、Ni 2+、Co 2+、Pt 2+、Pd 2+、或者四价金属离子如Sn 4+或Ti 4+;c 2:在碱性条件下,使化合物11发生水解反应,得到化合物13:d 2:使化合物13与氨基酸酯盐酸盐发生缩合反应,得到式III(a)化合物:其中M为2H,或者在与金属氯化物或乙酸根络合物发生反应后而成为金属离子,例如二价金属离子如Cu 2+、Fe 2+、Zn 2+、Mg 2+、Ni 2+、Co 2+、Pt 2+、Pd 2+、或者四价金属离子如Sn 4+或Ti 4+,其中R 3如权利要求1所定义;可选地,在碱性条件下,式III(a)化合物发生水解反应,生成相应的盐,即式III(b)化合物;或a 3:在缩合剂的作用下,化合物19与氨基酸酯盐酸盐发生缩合反应,得到化合物20:其中M为2H,或者在与金属氯化物或乙酸根络合物发生反应后而成为金属离子,例如二价金属离子如Cu 2+、Fe 2+、Zn 2+、Mg 2+、Ni 2+、Co 2+、Pt 2+、Pd 2+、或者四价金属离子如Sn 4+或Ti 4+,其中R 4如权利要求1所定义;可选地,在碱性条件下,式IV(a)化合物发生水解反应,生成相应的盐,即IV(b)化合物。
- 一种抗肿瘤组合物,包含:权利要求1-3中任一项所述的二氢卟吩衍生物或其可药用盐、以及药学上可接受的赋形剂;优选地,所述抗肿瘤组合物为注射制剂。
- 根据权利要求5所述的抗肿瘤组合物,其中,所述肿瘤包括良性肿瘤和恶性肿瘤;所述恶性肿瘤包括例如原位癌和癌转移;所述原位癌包括例如乳腺癌、肝癌、肺癌、结直肠癌;所述癌转移包括例如乳腺癌转移、肝癌转移、肺癌转移、结直肠癌转移。
- 权利要求1-3中任一项所述的二氢卟吩衍生物或其可药用盐在制备抗肿瘤药物中的用途;优选地,所述抗肿瘤药物为注射制剂。
- 根据权利要求7所述的用途,其中,所述肿瘤包括良性肿瘤和恶性肿瘤;所述恶性肿瘤包括例如原位癌和癌转移;所述原位癌包括例如乳腺癌、肝癌、肺癌、结直肠癌;所述癌转移包括例如乳腺癌转移、肝癌转移、肺癌转移、结直肠癌转移。
- 根据权利要求7或8所述的用途,其中所述抗肿瘤药物用于光动力治疗或者声动力治疗中。
- 根据权利要求9所述的用途,其中所述光动力治疗中采用波长为600-800nm例如660nm的光波,所述声动力治疗采用强度为1.88W/cm 2的超声。
- 一种二氢卟吩衍生物或其可药用盐与超声医疗系统的组合,其特征在于,所述二氢卟吩衍生物或其可药用盐为权利要求1-3中任一项所述的二氢卟吩衍生物或其可药用盐,所述超声医疗系统包括换能器声床和接触剂,其中,所述换能器声床包括底部和从底部向上延伸的壁部;所述底部在与目标的头、躯干和四肢相对应的位置处分别具有至少一个超声换能器,以用于向位于其上方的目标发射超声波;所述壁部在其与目标头部和四肢相对应的位置处分别具有至少一个超声换能器,以用于向目标发射超声波;所述接触剂用于在所述目标与所述超声换能器之间传递超声波。
- 根据权利要求11所述的组合,其特征在于,所述超声医疗系统还包括换能器模组,其中,所述换能器模组安装在所述换能器声床的上方,包括至少一个超声换能器,用于向位于其下方的目标发射超声波,所述接触剂也用于在所述目标与所述至少一个超声换能器之间传递超声波。
- 根据权利要求12所述的组合,其特征在于,所述换能器模组还包括数控运动装置,用于控制所述换能器模组在水平和/或竖直方向移动。
- 根据权利要求10-13中任一项所述的组合,其特征在于,所述超声波为脉冲波或连续波,优选地,所述超声波频率为0.3-3MHz; 优选地,所述超声波的声强为为0.1-3W/cm 2。
- 根据权利要求10-14中任一项所述的组合,其特征在于,所述接触剂是水和真空脱气冷/热水中的至少一种。
- 根据权利要求10-15中任一项所述的组合,其特征在于,所述超声医疗系统还包括可编程序逻辑控制器自动控制系统和接触剂供应系统,其中:所述接触剂供应系统与换能器声床相连接,用于向所述换能器声床供应接触剂;所述可编程序逻辑控制器自动控制系统分别与所述换能器声床、所述换能器模组以及所述接触剂供应系统相连接,用于控制经由所述接触剂供应系统向所述换能器声床供应接触剂,并用于控制所述换能器声床和所述换能器模组中的至少一部分超声换能器的操作。
- 根据权利要求16所述的组合,其特征在于,所述可编程序逻辑控制器自动控制系统还包括监视系统,用于显示至少以下内容之一:a.所述换能器声床和所述换能器模组中的至少一部分超声换能器的工作参数;b.目标内的病灶信息。
- 根据权利要求10-17中任一项所述的组合,其特征在于,所述二氢卟吩衍生物或其可药用盐通过权利要求4所述的方法制备获得。
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WO2014071138A1 (en) * | 2012-11-02 | 2014-05-08 | Lewis Thomas J | Disease detection and treatment through activation of compounds using external energy |
CN103396419A (zh) * | 2013-08-13 | 2013-11-20 | 海宁市绿升医药科技有限公司 | 肿瘤光动力治疗药二氢卟吩e6-15-乙酯及其制备方法 |
CN106046008A (zh) * | 2016-05-25 | 2016-10-26 | 中国人民解放军第二军医大学 | 二氢卟吩p6类氨基酸衍生物及其制备方法和用途 |
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