前言導讀
血管鈣化（vascular calcification）是動脈粥樣硬化、高血壓、糖尿病血管病變、血管損傷、慢性腎病和衰老等普遍存在的共同的病理表現。
主要表現為血管壁僵硬性增加，順應性降低，易導致心肌缺血、左心室肥大和心力衰竭，引發血栓形成、斑塊破裂，是心腦血管疾病高發病率和高死亡率的重要因素之一；亦是動脈粥樣硬化心血管事件、腦卒中和外周血管病發生的重要標志分子。
血管鈣化是指鈣質物沉積在血管壁的一種病變，會導致血管壁變硬，順應性降低。根據《冠狀動脈鈣化病變診治中國專家共識（2021版）》，冠狀動脈鈣化隨年齡增加而增加。此外，外周動脈的鈣化也是常見問題。無論是冠狀動脈還是外周動脈的鈣化，都是介入治療中非常棘手的病變。
Shockwave 概覽
近日，國家藥品監督管理局對外發布醫療器械批準證明文件（進口）信息，健適醫療的Shockwave血管內沖擊波“系列產品獲批上市，健適醫療的獲證產品包括設備主機、及用于治療冠狀動脈和外周動脈鈣化病變的多種型號導管。
去年3月，健適醫療與美國上市公司Shockwave Medical成立由健適控股的合資公司，引進全球頂尖的醫療新科技 --"血管內沖擊波"鈣化處理技術，由此加速國產化的進程。
筆者注意到，5月9日ShockWave Medical(股票代碼：SWAV)公布財報，公告顯示公司2022財年第一財季歸屬于母公司普通股股東凈利潤為1452.10萬美元，同比增長161.53%；營業收入為9363.10萬美元，同比上漲193.51%。
ShockWave Medical, Inc.成立于2009年6月17日,是一家專注于開發和商業化產品的醫療器械公司，旨在改變鈣化心血管疾病的治療方式。他們的目標是通過其用于治療鈣化斑塊的聲壓力波的差異化和專有的局部遞送來建立醫療器械治療動脈粥樣硬化性心血管疾病的新標準，它們稱為血管內碎石術（“IVL”）。
專利分析
筆者針對ShockWave所涉及的專利情況，進行了檢索，其結果進行如下展示：
技術解讀
Shockwave血管內沖擊波技術的靈感來源于腎結石體外沖擊波治療，通過球囊導管把脈沖聲壓波輸送至鈣化部位，把鈣化的斑塊“震松”，使血管恢復彈性及血流，重塑病變血管的同時，避免了對血管內膜的損傷。
產品由球囊、導管軸、導管座、充盈端口、導絲出口、連接器和脈沖發射器組成。
產品基于體外碎石沖擊波原理改進而來，將聚焦式高強度 能量改為發散式低強度能量，通過血管內導管方式導入外周血管對鈣化病變部位進行松解，以緩解血管狹窄程度或便于后續治療。
產品導管上含有若干液電式能量波源（脈沖發射器），通過接受發生器傳遞的電能轉化為機械能向外輸出沖擊波能量。能量波源外部含有球囊，與球囊加壓裝置配合使用可用于擴張狹窄部位血管，球囊內部可注入生理鹽水/造影劑的混合液用于傳遞沖擊波能量。
Shockwave血管內沖擊波技術相關產品的結構組成和工作原理可參考如下視頻：
專利概覽
筆者對Shockwave的相關專利根據類別分別進行了整理和剖析，這里筆者從眾多專利中選擇了若干進行了解析，相關相關結果如下：Shockwave的完整專利清單和分析筆者也已開展完成，如感興趣可以與筆者取得聯系，共同交流學習：
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Low profile electrodes for an angioplasty shock wave catheter |
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Currently, angioplasty balloons are used to open calcified lesions in the wall of an artery. However, as an angioplasty balloon is inflated to expand the lesion in the vascular wall, the inflation pressure stores a tremendous amount of energy in the balloon until the calcified lesion breaks or cracks. That stored energy is then released and may stress and injure the wall of the blood vessel. |
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Described herein are low-profile electrodes for use with an angioplasty shockwave catheter. A low-profile electrode assembly may have an inner electrode, an insulating layer disposed over the inner electrode such that an opening in the insulating layer is aligned with the inner electrode, and an outer electrode sheath disposed over the insulating layer such that an opening in the outer electrode sheath is coaxially aligned with the opening in the insulating layer. This layered configuration allows for the generation of shockwaves that propagate outward from the side of the catheter. In some variations, the electrode assembly has a second inner electrode, and the insulating layer and outer electrode may each have a second opening that are coaxially aligned with the second inner electrode. An angioplasty shockwave catheter may have a plurality of such low-profile electrode assemblies along its length to break up calcified plaques along a length of a vessel. |
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Shockwave catheter system with energy control |
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A still further important aspect of prior art attempts to use shock waves from electrical arcs for therapeutic purposes is that from the time the high voltage is first applied to the electrodes to the time in which the arc occurs there is a dwell time (Td) that is highly variable from one high voltage application to the next. To account for the dwell times that are long, prior art strategies have relied upon high voltage applications where all high voltage pulse durations or pulse widths are of the same length and of a length sufficient to extend through the longest of the anticipated dwell times plus the associated arc and steam bubble. As a result, when the dwell times are shorter than the maximum, the high voltage application durations are longer than necessary and can unnecessarily extend the arc and the steam bubble well beyond a time required to produce a shock wave of maximum intensity. The result is wasted energy, extended electrode erosion, and unnecessary heating of the adjoining tissue. |
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A system that breaks calcium in a liquid includes a catheter including first and second electrodes arranged to receive there-across a high electrical voltage at an initial low current. The high electrical voltage causes an electrical arc to form across the electrodes creating a gas bubble within the liquid, a high current to flow through the electrodes, and a mechanical shock wave. A power source provides the electrodes with the high electrical voltage at the initial current and terminates the high electrical voltage in response to the high current flow through the electrodes. |
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結 語
目前，對于IVL而言而言，國內已有不少廠家正在進行相關研發和臨床試驗，不過目前技術依然以Shockwave等國外企業為主，不過隨著國內重視程度不斷提高的情況下，中國公司蓄勢待發，在一片被普遍看好的市場中開始暗流涌動，雖然目前為止還沒有真正意義上的國產IVL成品上市，但是隨著各個“卡脖子”技術不斷攻克，國產IVL一定會在近幾年實現重大突破和問世。
目前，國內各大IVL領域醫療廠商還會將Shockwave等重要競品作為標桿和對照，但是隨著各大國內廠商聯動產學研醫生多方力量，不斷創新，必將推動中國IVL業更智能化、精準化、便攜化的發展，也會逐步擺脫國外競品帶來的壓力和技術障礙，不過，國外巨頭公司和國內新興企業在知識產權方面布局更加緊密，IVL賽道上的各個國內廠商之間的競爭也會逐漸激烈，屆時相關知識產權問題也必將會成為各大IVL廠商的研究重點課題，后續相關產品的的研發和專利事務值得持續關注。
