201043284 六、發明說明： 【發明所屬之技術領域】 [0001] 本發明係相關於各種注射導管之領域。更嚴謹的來說， 本發明係相關於一種用來將藥劑引入一種基質之注射導 管以及一種用來將藥劑引入一種基質之方法。 【先前技術】 [0002] 心血管疾病是世界上主要致死原因之一。心臟病發作及 心肌梗塞（Heart attacks and myocardial in- 〇 可導致立即死亡或甚高解導致併發症，以 及對心臟造成永久之傷殘》預防及治療這些疾病便成為 格外重要，也因而已有無數的努力投入在臨床的照護及 治療這些心臟性疾病。 / [0003] 再生醫學（Regenerative medicine)是一種現代研究方 法之一以減少心臟器官之障礙’參見：（Sherman，Ba_ sic Appl· Myol· 13(1) 11-14)«^這包含了將各種治療用 液體利用器械注入到心臟肌肉之内。有許多種治療用之 〇 液體皆可利甩到這參技術來實施引入，‘例如，基於幹細 胞治療之許多化合物液體。這些治療法應該很有前途， 只是目下尚遭遇到一些尚未解決的問題點。問題之一是 各種治療用液體注入器官之後，受到器官多孔性的影響 ，其停留率甚低。此停留率依注射方式的不同皆不會高 於5%到 10% (參閱Bartunek et al，Delivery 〇f201043284 VI. Description of the Invention: TECHNICAL FIELD OF THE INVENTION [0001] The present invention relates to the field of various injection catheters. More rigorously, the invention relates to an injection catheter for introducing a medicament into a substrate and a method for introducing a medicament into a substrate. [Prior Art] [0002] Cardiovascular disease is one of the leading causes of death in the world. Heart attack and myocardial infarction (Heart attacks and myocardial in- 〇 can lead to immediate death or high resolution leading to complications, as well as permanent disability to the heart) Prevention and treatment of these diseases has become particularly important, and thus there are countless Efforts to invest in clinical care and treatment of these heart diseases. / [0003] Regenerative medicine is one of the modern research methods to reduce the obstacles of heart organs. See: (Sherman, Ba_ sic Appl· Myol· 13 (1) 11-14) «^ This involves injecting various therapeutic fluids into the heart muscle. There are many kinds of therapeutic liquids that can be used to implement the introduction, 'for example, based on Many compound liquids for stem cell therapy. These treatments should be promising, but there are still some unresolved problems. Some of the problems are that after the various therapeutic fluids are injected into the organs, they are affected by the porosity of the organs, and the retention rate is very high. Low. This retention rate will not be higher than 5% to 10% depending on the injection method (see Bartunek et al, Delivery 〇 f
Biologies in Cardiovascular Regenerative Medicine, Clinical Pharmacology & Therapeut-ics’ 2009 )。這樣低的停留率代表這些治療用液體無 099113627 表單編號A0101 第3頁/共30頁 0993231107-0 201043284 法最佳化地發揮它們的效率。 [0004] [0005] [0006] 這許多種治療用液體通常皆需利用到一些器械，例如注 射導管（injection catheters)來實施將其注入。 這些器械’或是注射導管之設計好壞，影響到注射的效 力及品質。在 Journal 〇f Molecular and Cellular Cardiology， 2008， 44， 473-476 中 ，描述若干 注射器材因其注射之方式不同產生的一些缺失（其將注 射之方式分為心外膜、心内膜、心冠動脈内或靜脈内四 類）。 其在心内膜注射方式中強調，因為可能會刺穿心肌而有 令病人致死的風險》 EP 1 301 228中揭示一梭專為心臟使用的器材。該器 材是一個注射導管，而在該注射導管的媾點上，也就是 其與心肌作接觸之部位，在其一個面上設置有一個開口 。一種細胞性之材料可以經由此開口注入到心肌上。然 而’該細胞性材料係被注入到心肌内的—個孤點位置而 不會有利於該細胞性材料之散布。除此以外，在當針頭 被抽出時’會有一些的該種細胞性材料落入在心室内部 。將細胞性材料注入到心肌上的一個孤點位置，不止是 其停留率甚低及有刺穿心肌的風險，它還可能導致水腫 US 2007/005018揭示了一種直接的注射導管系統，其配 置有彎曲針具(310)之中空插管（41〇)其端點上設置複 數個開口（734)。這些元件係用來像錨一樣將插管固定 在心肌上，這樣可以減低插管刺穿心肌的風險。該元件 099113627 表單編號A0101 第4頁/共30頁 0993231107-0 201043284 上所設置的複數個開口用來將藥劑以低速率方式來作注 入。然而，該器材無法讓人控制藥劑液體之注射壓力及 其在心肌内之散佈。更由於受限於該彎曲針具（31〇)之 結構而無法設置太多烟σ於其上，而不造成其剛性過 低而妨害其不能順利刺入心肌中者。這些因素使其無法 能快速地、及在沒有產生水腫m，來注人大量的 藥劑。 圆因此有-㈣求，那就是，該料管要能夠注射一 〇 種藥劑進人到—種基質如生物組織中，而該藥劑可以在 該基質之中散佈，且不會有刺穿心肌的風險，而在此同 時該種藥劑可以在該基質内有最高的停留率。 另外對-他射導管的要求是，㈣料#在#能力將 -種藥劑在刺人區域内且利用其大半的穿刺接觸面積來 將其/主人到基質之#，卻又可以降低在注射位置發生水 腫之風險。 【發明内容】 〇 [_本剌克服了全部或部份習知技藝中的缺點並可產出習 知技藝器材中無法產生的優點。 [0009] 099113627 本發明將_狀-絲質之靖導管似進針對前述 第一項之習知技藝缺點而產生。該注射導管，其至少包 含-個或多個内管以及—個輸導元件，該内管的功能是 在基質外部導引該輸導元件，其特徵為，該輸導元件至 v包s-個套η穿孔元件，該套管設置在該穿孔 兀件之週圍’且至少包含有複數綱口於其末梢之-個 或以上之側面上。該輸導元件至少包含—段硬質穿刺區 表單编號峨 ^1/^30! 〇9932311〇7-0 201043284 ，、二D _來在較麵設計控繼件下注入藥劑 =可以她的控__在該基質中有較佳之散佈。 ★之故才有可能注射大份量之藥劑進人到基質之中， 而不會發生刺穿基質之問題。 [0010] [0011] 針對改進則述第前述第二項之習知技藝缺點，產生了本 發明將藥劑通過—個注射導管狀—種基f之方法。該 方法至少包含以下之步驟： 將°玄/主射導管之末梢（distal tip)定位到基質之表 面， —利用㈣之方絲獅該注料管之料元件，後者 至少包含-個穿孔元件以及—個套管，該套管為設置在 該穿孔元件之外週者，以及在該注射導管之單—或複數 個之内管内m含有複數個肖口於其末梢之至少一 個側面上’ -將該一個穿孔元件刺入到基質之中，並以滑動方式推 動設置於穿孔元件外方之套管， Γ. . ...... •將該穿孔元件自基質中抽回卜以及 -將藥劑通過該套管注射到該基質中。 針對改進前述另一項之習知技藝缺點，本發明完成了應 用注射導管將藥劑引入一種基質之新方法。有利的是， 該基質為心肌。有利的是，該藥劑是一個含有自幹細胞 滋生出來之細胞之液體。 【實施方式】 名詞「導管」（catheter)在此處是指醫務用的中空管 以插入一管道、體腔、靜脈或動脈中，用來注射或抽取 099113627 表單編號A0101 第6頁/共30頁 0993231107-0 [0012] 201043284 體液，或是用來維持一個通道之開啟者。 [001¾名詞「内管」（Lumen)是指一個中空管件的開口，其内 部之空間，其可以容納-個第二元件或者注射一種液體 進入到一個管道、體腔、靜脈或動脈中者。 [0014] 名詞「輸導元件」（delivery element)在此處是指一 根倶有末端開口的管子，而此開口上可以安裝一個蓋子 又稱Luer鎖（Luer Lock或旋鎖接口）。這個蓋子用來 可靠地封閉輸導元件的近端開口。Biologies in Cardiovascular Regenerative Medicine, Clinical Pharmacology & Therapeut-ics' 2009). Such a low retention rate means that these therapeutic fluids are no more than 099113627 Form No. A0101 Page 3 of 30 0993231107-0 201043284 The method optimizes their efficiency. [0004] [0006] Many of these therapeutic fluids typically require the use of some instruments, such as injection catheters, to effect infusion. The design of these devices or injection catheters affects the efficacy and quality of the injection. In Journal 〇f Molecular and Cellular Cardiology, 2008, 44, 473-476, some of the injections are described as being different due to the manner in which they are injected (which divides the injection into the epicardium, endocardium, and coronary artery). Four types of internal or intravenous). It is emphasized in the endocardial injection mode that there is a risk of death from the patient because it may pierce the myocardium. EP 1 301 228 discloses a device for the heart. The device is an injection catheter, and an opening is provided on one side of the injection catheter at the point of the injection, that is, the portion in contact with the myocardium. A cellular material can be injected into the myocardium through this opening. However, the cellular material is injected into the locus of the myocardium and does not contribute to the spread of the cellular material. In addition, some of the cellular material will fall into the ventricle when the needle is withdrawn. Injecting cellular material into a solitary point on the myocardium is not only a low rate of retention and the risk of piercing the myocardium, it may also lead to edema. US 2007/005018 discloses a direct injection catheter system with a configuration The hollow cannula (41〇) of the curved needle (310) is provided with a plurality of openings (734) at its end points. These elements are used to anchor the cannula to the myocardium like an anchor, which reduces the risk of the cannula piercing the myocardium. This component 099113627 Form No. A0101 Page 4 of 30 0993231107-0 201043284 The multiple openings provided are used to inject the drug at a low rate. However, the device does not allow one to control the injection pressure of the drug liquid and its spread within the myocardium. Further, due to the structure of the curved needle (31〇), it is impossible to set too much smoke σ thereon without causing the rigidity to be too low to hinder the smooth penetration into the myocardium. These factors make it impossible to inject a large amount of medicament quickly and without edema m. The circle therefore has a (four) request, that is, the tube should be able to inject a drug into a substrate such as a biological tissue, and the agent can be dispersed in the matrix without piercing the myocardium. Risk, while at the same time the agent has the highest retention rate in the matrix. In addition, the requirement for the -he catheter is that the (four) material ## capability will be in the stinging area and utilize most of its puncture contact area to bring its/master to the substrate #, but can be lowered at the injection position. The risk of edema. SUMMARY OF THE INVENTION [_ 本剌 Overcomes all of the disadvantages of the prior art and can produce advantages that are not possible in conventional art equipment. [0009] 099113627 The present invention produces a _----------------------------------------------------- The injection catheter comprises at least one or more inner tubes and a transport element, the inner tube functioning to guide the transport element outside the substrate, characterized in that the transport element to the v package s- a set of n-perforating elements, the sleeve being disposed around the perforated member and having at least a plurality of sides on one or more sides of the distal end thereof. The guiding element includes at least a segment of the hard puncture zone form number 峨^1/^30! 〇9932311〇7-0 201043284, and two D _ to inject the drug under the face design control component = can control her _ There is a better dispersion in the matrix. ★ It is possible to inject a large amount of the drug into the matrix without the problem of piercing the matrix. [0011] With regard to the conventional technical disadvantages of the second item described above, the method of the present invention for passing a medicament through a tube-like base f is produced. The method comprises at least the steps of: positioning a distal tip of the smear/main injection conduit to the surface of the substrate, using (4) a square lion, the material element of the injection tube, the latter comprising at least one perforating element and a sleeve, the sleeve being disposed outside the perforating member, and wherein the tube has a plurality of channels on at least one side of the distal end of the injection tube The one perforating member penetrates into the substrate and slides the sleeve disposed outside the perforating member in a sliding manner, Γ........ • withdraws the perforated member from the substrate and - the medicament Injection into the matrix through the cannula. In response to the above-described conventional technical disadvantages of the other, the present invention accomplishes a new method of introducing an agent into a substrate using an injection catheter. Advantageously, the matrix is a myocardium. Advantageously, the agent is a liquid containing cells derived from stem cells. [Embodiment] The term "catheter" as used herein refers to a hollow tube for medical use for insertion into a tube, body cavity, vein or artery for injection or extraction. 099113627 Form No. A0101 Page 6 of 30 0993231107-0 [0012] 201043284 Body fluid, or used to maintain the opening of a channel. [0013⁄4] The term "Lumen" refers to the opening of a hollow tubular member, the inner space of which can accommodate a second component or inject a liquid into a tube, body cavity, vein or artery. [0014] The term "delivery element" as used herein refers to a tube having an open end, and a cover can be attached to the opening, also known as a Luer lock (Luer Lock or a twist lock interface). This cover is used to securely close the proximal opening of the delivery element.
[0015] 該基質有一個厚度為E。由圖1A中可見輸導元件2刺入基 質8中’其刺入之深度隨該輸導元件之p點而異。今將點p 與基質表面之最短距離定義為深度D。最大深度j)max則 位於深度D為最大處之Pmax點。名詞「刺入深度」（ penetration depth)在此處是指最大深度Dmax與基質之 厚度E比之百分數》[0015] The substrate has a thickness of E. It can be seen from Figure 1A that the transport element 2 penetrates into the substrate 8' the depth of its penetration varies with the p-point of the transport element. The shortest distance between point p and the surface of the substrate is now defined as depth D. The maximum depth j)max is located at the Pmax point where the depth D is the maximum. The term "penetration depth" as used herein refers to the ratio of the maximum depth Dmax to the thickness E of the matrix.
-- . ：V-- . :V
[0016] 圖1B顯示一個輸導元件2的套管末梢處的剖面圖。該套 管14有一内徑ID及一外徑QD »該套管14上，至少在 其一邊’設有至少一個開口 6:½開口 6為一3D構造而 有一外表面18及一内表面20，延伸高度Η。名詞「表面 」在本發明中是指該開口 6之外表面18。該開口有一 内表面20 ’内表面2〇可以大於、等於或小於外表面18 〇 該開口之形狀在本發明中是指該套管14外表面18處之 形狀。 [〇〇17]圖1人所示出者，為針對改進前述第一項之習知技藝缺點 的一種注射導管1用來將藥劑引入一種基質8之本發明 099113627 表單編號Α0101 第7頁/共30頁 0993231107-0 201043284 ，其至少包含-個或多個内管10以及—個輸導元件2， 該-個或多個内管的功能是在基質8外部導弓丨該輸導元件 2’其特徵為，該輪導元件2至少包含_個套管14以及— 個穿孔兀件12 ’該套管14為設置在該穿孔元件12 之外週m少包含複數朗σ6於其末梢16之至少 一個侧面上。 099113627 [0018] [0019] 該套管14之末梢上之複數個開口 16之設置，可 以致使藥劑在該基質内有一個依照設計而形成的分佈， 這也可使該藥劑在該基質中有辣佳之停留率。該套管 14之末梢16相當於該套管14在末梢端方向之最後3 . 該末梢16相當於自最接近該末梢開口 22之開口到 最遠離該末梢開口 22開口之間之距離之長度。 發明’該末卿口 22並*被視為_個開口 6 依據本 依據一種有利的實施例，言亥套管14 ±，至少可 包含複數個開口 6 ，❿其表面積為相同者。另外一 種選擇則是，該套管14上，至少寸包含複數個開口 6，而此魏個開口其表面積為在往末梢端方向上， 至少在其末梢16之部份區内為遞增或遞減者。 依據-種有利的實施例，複數個開口 6之面積為介 於〇 〇1随2及3. 〇 之間。有利的是將該複 數個開口 6之面積設計成〇 〇〇1心至U酿2之間 之值。該套管14之末梢16上之複數個開口 6之 總面積可介於0.002 到3 〇随2之間。名詞「 末梢16上之複數個開D 6之總面積」係指在該套管14 上於末梢上之每一個開口之面積之總和。更為有利是， 表單編號Α0101 第8頁/共3〇頁 0993231107-0 201043284 [0020] Ο ο [0021] 末梢16上之複數個開口 6之總面積為介於〇 2 及3. 0 mm2之間，最為有利是，末梢4上之複數個 開口 6之總面積為介於〇·3 mm2and 2 〇關2之間。 這些開口的平均面積值可以使該藥劑在該基質中作有規 晝之分佈，這可以有助該在基質内的散佈而可以避免該 注射點發生水腫現象（edema)。 该套管14及該穿孔元件12可以有一個外直徑介於 20 gauge至34 gauge之間，而以介於25 gauge至32 gauge之間為有利。因此，該套管14 及該穿孔元件12之外直徑可以設計為介於〇 184 mm 及0. 9 0 8 mm之間。有利的是，該套管14及今穿 孔元件12之外直徑設計為介於0.235 及0.514 mm之間。一般而言，該套管14及該穿孔元件12之内 徑可以介於0.0826 mm及0.603 mm之間；有利 的是，該套管14及該穿孔元件12之内學設計在介於 0. 108 mm及0 . 260 mm之間。該注射導管J之長度 ，從其末梢開口到它的近瑞點可以大於1〇〇(：111。 在另外一個有利的實施例中，該複數個開口 6可為不 同之形狀如蛋形、方形、圓形、長方形、三角形、橢圓 形或者其形如剪口、長菱形的、蜷線狀的或是如螺旋狀 的。該複數個開口 6可設置於該輸導元件2之末梢16上之 所有邊上。此外，該開口需要能允許直徑為1〇至6〇口 m之細胞通過。 [0022] 該套管14係設置在該穿孔元件12之外方週圍。該 穿孔元件12係用於刺穿基質8, 並在基質8内引導 099113627 表單編號A0101 第9頁/共30頁 0993231107-0 201043284 該套管14之運動。該穿孔元件8可由一種俱有形狀記憶 能力之材料製成。名詞「倶有形狀記憶能力之材料 」係指一種材料，其有能力形狀記憶其初始形狀，並能 在其變形過後再恢復其初始形狀者。這種俱有形狀記 憶月b力之材料可以是一種錄及鈥之合金、一種銅基 或是一種鐵基之合金。有利的是，該有形狀記憶能力 之材料是一種鎳及鈦之合金，例如說是NiTINOL ( 錄鈇諾）。該鎳及鈦之合金也可以含有少量之銅、鐵、 銳（niobium )、纪金（palladium)或銘金（ platinum )之成你。該穿·(元件12可為一個空心或實 心之針具或金屬線。該穿孔元件12可至少包含一尖頭以 利其剌入基質8。該套管14可由一韃高分子材料、一 種複合材料、一個金屬材料或是一種合余材料來製成 。譬如說，該套管可由，但不限於由，聚亞醯胺（[0016] FIG. 1B shows a cross-sectional view of the end of the sleeve of a transport element 2. The sleeve 14 has an inner diameter ID and an outer diameter QD. The sleeve 14 has at least one opening 6 on its side. The opening 6 is a 3D configuration and has an outer surface 18 and an inner surface 20. The height is extended. The term "surface" in the present invention refers to the outer surface 18 of the opening 6. The opening has an inner surface 20' which may be larger, equal to or smaller than the outer surface 18. The shape of the opening is referred to in the present invention as the outer surface 18 of the sleeve 14. [0017] The person shown in Fig. 1 is an invention for improving the disadvantages of the prior art of the first item, an injection catheter 1 for introducing a medicament into a substrate 8 of the invention 099113627 Form No. 1010101 Page 7 / Total 30 pages 0993231107-0 201043284, which comprises at least one or more inner tubes 10 and a transport element 2, the function of which is to guide the transport element 2' outside the substrate 8. It is characterized in that the wheel guide element 2 comprises at least one sleeve 14 and one perforated element 12'. The sleeve 14 is disposed outside the perforated element 12 and contains at least a plurality of squares σ6 at least at its distal end 16 On one side. [0019] [0019] The plurality of openings 16 in the distal end of the sleeve 14 are arranged to cause a distribution of the medicament within the matrix according to design, which also allows the medicament to be spicy in the matrix Good stay rate. The distal end 16 of the sleeve 14 corresponds to the last 3 of the sleeve 14 in the distal end direction. The distal end 16 corresponds to the length from the opening closest to the distal opening 22 to the distance between the opening distally from the distal opening 22. The invention is considered to be an opening 6. According to an advantageous embodiment, the casing 14 can comprise at least a plurality of openings 6 having the same surface area. Alternatively, the sleeve 14 includes at least a plurality of openings 6 which have a surface area in the direction toward the distal end, at least in the portion of the distal end 16 thereof which is incremented or decremented. . According to an advantageous embodiment, the area of the plurality of openings 6 is between 〇 1 and 2 and 3. 。. Advantageously, the area of the plurality of openings 6 is designed to be between 心1 heart and U. The total area of the plurality of openings 6 in the distal end 16 of the sleeve 14 can be between 0.002 and 3 inches. The term "the total area of the openings D 6 on the tip 16" refers to the sum of the areas of each of the openings on the sleeve 14 on the tip. More preferably, the form number Α0101, page 8 / total 3 page 0993231107-0 201043284 [0020] ο ο [0021] The total area of the plurality of openings 6 on the tip 16 is between 〇2 and 3. 0 mm2 Most advantageously, the total area of the plurality of openings 6 on the tip 4 is between 〇·3 mm2 and 2 〇2. The average area value of these openings provides for a well-distributed distribution of the agent in the matrix which aids in the dispersion within the matrix to avoid edema at the injection site. The sleeve 14 and the perforating member 12 can have an outer diameter of between 20 gauge and 34 gauge, and advantageously between 25 gauge and 32 gauge. Therefore, the outer diameter of the sleeve 14 and the perforating member 12 can be designed to be between 184 184 mm and 0.98 8 mm. Advantageously, the outer diameter of the sleeve 14 and the present perforating element 12 is designed to be between 0.235 and 0.514 mm. In general, the inner diameter of the sleeve 14 and the perforating member 12 may be between 0.0826 mm and 0.603 mm. Between mm and 0. 260 mm. The length of the injection catheter J may be greater than 1 〇〇 (: 111) from its distal opening to its proximal point. In another advantageous embodiment, the plurality of openings 6 may be of different shapes such as an egg shape or a square shape. , a circle, a rectangle, a triangle, an ellipse or a shape such as a cut, a rhomboid, a rifle, or a spiral. The plurality of openings 6 may be disposed on the distal end 16 of the transport element 2. In addition, the opening needs to allow passage of cells having a diameter of 1 〇 to 6 m m. [0022] The sleeve 14 is disposed around the outside of the perforating member 12. The perforating member 12 is used for Piercing the substrate 8 and guiding it within the substrate 8 099113627 Form No. A0101 Page 9 / Total 30 pages 0993231107-0 201043284 The movement of the sleeve 14. The perforating element 8 can be made of a material having a shape memory capability. "Materials with shape memory ability" means a material that has the ability to shape its original shape and to restore its original shape after it has been deformed. The material of shape memory can be a kind of material. Record and 鈥Gold, a copper base or an iron-based alloy. Advantageously, the shape memory capable material is an alloy of nickel and titanium, such as NiTINOL. The alloy of nickel and titanium can also be used. Contains a small amount of copper, iron, niobium, palladium or platinum. The wearer (component 12 can be a hollow or solid needle or metal wire. The perforated element 12 The tip can be at least included to facilitate the intrusion into the substrate 8. The sleeve 14 can be made of a polymer material, a composite material, a metal material or a replenishing material. For example, the sleeve can be But not limited to, by polyamine
Polyimide)、聚謎醚酮（p〇iyetheretherketone， PEEK)或不鏽鋼來製成。有利的是，該套管14之末 梢16有一開口面積為大於2%者。名詞「開口面積 」是指該複數個開口 6之總面積與該套管14之末梢上之 總面積之百分比。 依據本發明，這樣的開口面積可使該注射導管發揮 最優良之使用效果。更有利的是，該套管14之 末梢16之開口面積為介於2%至5〇%者。該穿孔元 件12仍然俱備充份的剛性而可剌入基質8且發揮最大之 藥劑注入效果。該套管14之末梢16之開口面積因此可 大於20% ，有利的是為介於2%至者。實質上， 本發明將β亥輸導元件2 :計成為將一個套管14設置於一個 099113627 表單編號A0101 第〗〇頁/共30頁 0993231107-0 201043284 [0023] Ο [0024] ο 穿孔元件12之外圍，這正可以補正在一般情形下當一個 輸導元件的開口大於20%就會有剛性不足的缺點。 依據一種有利的實施例，該複數個開口 6可以均勻 分配在該套管14之末梢16上。另一種選項是，該 複數個開口可以隨機地設置於該輸導元件2之套管14之 末梢16上。該複數個開口 6「均勻地」分佈於該套管14 之末梢16之至少一個邊上，其每一個開口 6皆與其鄰近之 開口成等距者。另一個選項是，該複數個開口 6 「均 勻地」分佈於該套管14之末梢16之一段之全週邊上 而皆與其鄰近之開口成等距者。另一個選項是，該複數 個開口 6「均勻地」分佈係指其每一個開口 6皆在往末梢 端方向上、或在其橫向方向上與其鄰近之開口成等距者 〇 依據本發明之一項有利之實施例，該注射導管1至 少包含有一個機制來控制該輸導元件2刺入基質8中 之深度者。該控制輸導元件進入到基質中之刺入深度之 機制之存在，可以防止刺穿該基質之相關風險之發生。 因此，該控制輸導元件進入到基質中之刺入深度之機制 之存在可以掌握該控制輸導元件2進入到基質中之刺入深 度在該基質厚度之25%至75%之間。該藥劑，可以因此 之故，在完全安全的情況下被注射到該基質之中。 尤其，該控制輸導元件進入到基質中之刺入深度之裝置 可以是一個倶有記憶功能之管曲元件、一個配置有止動 設計之元件或是一個可被超音波技術所能偵知之元件者 099113627 表單編號Α0101 第11頁/共30頁 0993231107-0 [0025] 201043284 [0026] [0027] 有利的疋，該控制刺入深度之裝置可以是一個倶有記 t«力此之彎曲元件。尤其是，該倶有記憶功能之彎 曲凡件為該輸導元件2，後者至少包含一個套管14 以及一個穿孔元件12，該14套管為設置在該穿孔 疋件〗2之外週者，以及其至少包含複數個開口 6 於其末梢16之至少一個侧面上者。因此之故，該彎 曲的輸導元件2刺入到該基質8令的深度，就是由 該穿孔元件12的彎曲度來控制的。該彎曲的穿孔元 件12的彎曲度是定義為，當該注射導管已定位到基 質上時之其長方向条之中心軸線，與當該彎曲的穿孔 元件12進入到基質中就定位後該穿孔元件12之中 。軸線’兩者間所形成之夾角。有利的是，將該夹角 設計成介於6〇 2及丨，之間，而搞蘭該夾角設 -十成介於80及i20e之間更為有利。尤其可以將該 夾角設計成介於85。及1〇〇。之間。 另外一種選擇則是，該控制刺入深度之機如可以是一個 配置有止動設計之元件。<其是，該m有記憶功能之 著曲元件為該輸導元件2，後者至少包含一個套管μ以 及一個穿孔元件12,該14套管為設置在該穿孔元件 12之外週者，以及其至少包含複數個開口6於其末梢^之 至少-個側面上者。因此’該輸導元件可以在它的近端 點配置一個止動設計來限制其刺入到基質令之深度。 另外一種方式就是利用一個可被超音波技術所能偵知之 元件，來作為該控制輸導元件刺入深度之裝置。尤其 是，該可被超音波技術偵知之元件即為該輸導元件 099113627 表單編號A0101 第12頁/共30頁 0993231107-0 [0028] 201043284 ，其至少包含一個套管14以及一個穿孔元件1 2 ，該套管為設置在該穿孔元件之外週者，以及其至 少包含複數個開口 6於其末梢16之至少一個侧面上者 〇 [0029] 該注射導管可以裝設一個泵浦以控制注射藥劑之壓力。 Ο 利用該泵浦可以在注射導管之近端點處維持一個定 壓。在注射時維持一個定壓以及在輪導元件2之末梢 16上設置複數個開口 6來使藥劑作有控制之分佈，這便 可以減少、限制、甚至消除在注射點區域會發生水腫之 風險。除此以外，該藥劑在導管中之流速也不會過高 。因此’依據本發明的一個有利的實施例，藥劑在導管 中之流速可以是小於每分鐘6 ml，有利㊉是，該藥劑在 導管中之流速是小於每分鐘3 ml者。 [0030] Ο 針對改進前述第二項之習知技藝缺點而，產生了本發 明將藥劑通過一個注射導管引入一種基質之方法，那 就是： I w ~將該注射導管之末梢（distal tip)定位到基質之 表面 ， -利用滑動之方式來推動該注射導管1之輸導元件2, 後者至少包含一個穿孔元件12以及一個套管14， 該套管14為設置在該穿孔元件12之外週者，以及 在該注射導管1之單一或複數個之内管1〇内， 至少包含有複數個開口 6於其末梢16之至少一個側面 上， 一將該穿孔元件12刺入到基質8之中，並以滑動 099113627 表單編號A0101 第13頁/共.30頁 0993231107-0 201043284 方式推動設置於穿孔元件12外方之套管12， -將該穿孔元件12自基質8中抽回，以及 -將藥劑通過該套管14注射到該基質8中。 [0031] [0032] [0033] [0034] 依據一個有利的實施例，該注射導管可以裝設一個泵 浦以控制藥劑之注射壓力。利用該泵浦可以在該輸 導元件2之末梢16上維持一個定壓。依據一個本發明 的有利的實施例，該注射導管之近端點處注射藥劑之壓 力，在注射之全過程中皆大致維持恆定者。在注射時 維持一個定壓以及使藥劑作有控制之分佈，可以減少 、限制、甚至消除在注射點區域會發生水腫之風險。除 此以外，該藥劑在導管中之流速也不可能會過高。因 此，依據本發明的一個有利的實施例，藥劑在導管中之 流速可以是小於每分鐘6 ml，有利的是，該藥劑在導管 中之流速是可以小於每分鐘3 ml者。 依據本發明的另一個有利的實施例，其注射1.0 ml 量之藥劑之時間為20秒至3分鐘。 依據本發明之另一項有利之實施例，本發明之方法中 可以也包含有一個步驟那就是來控制該輸導元件2刺入 基質8中之深度者。有利的是，其刺入基質8中之深度 為介於該基質厚度之25%至75%者。控制進入到基質中 之刺入深度之機制之存在，可以防止刺穿該基質8之相關 風險之發生。該藥劑，可以因此之故，在完全安全的情 況下被注射到該基質之中。 依據一種有利的實施例，本發明之方法所用之該套管 099113627 表單編號A0101 第14頁/共30頁 201043284 14上，至少可包含複數個開口 6 。有利的是，將 該複數個開口 6之面積設計成0.001 mm2至2.0 mm2 之間之值。有利的是，將該複數個開口 6之面積設計 成0.001 mm2至2.0 mm2之間之值。該套管14之末 梢16上之複數個開口 6之總面積可介於0.002 mm2到3.0 mm2之間。更為有利是，末梢16上之複數 個開口 6之總面積為介於0.2 mm2及3.0 mm2之間 ，最為有利是，末梢4上之複數個開口 6之總面積 為介於0.3 mm2and 2.0 mm2之間。這些開口 6的面積 值可以使該藥劑在該基質中作均勻之分佈，這可以有助 該在基質内的散佈而可以避免在該注射點發生水腫現象 (edema)。 [0035] ❹ [0036] 依據在另外一個有利的實施例，該複數個開口 6可為 不同之形狀如蛋形、方形、圓形、長方形、三角形、橢 圓形或者其形如剪口、長菱形的、蜷線狀的或是如螺旋 狀的。該複數個開口 6可設置於該輸導元件14之末梢16 上之所有表面上。該複數個開口 6可使藥劑在一種控制 中的情況下注入基質8中。 該穿孔元件12係用於刺穿基質8，並在基質8内 引導該套管14之運動。該穿孔元件12可為一個空心之 針具或金屬線。該穿孔元件12可至少包含一尖頭以利其 剌入基質8。該穿孔元件12可由一種俱有形狀記憶能力之 材料製成。這種倶有形狀記憶能力之材料可以是一 種錄及鈦之合金、一種銅基或是一種鐵基之合金。有 利的是，該有形狀記憶能力之材料是一種鎳及鈦之 099113627 表單編號A0101 第15頁/共30頁 0993231107-0 201043284 合金，例如說是NiTINOL (鎳鈦諾）。該鎳及鈦之合 金也可以含有少量之銅、鐵、鈮（niobium )、鈀 金（palladium)或麵金（platinum )之成份。該 套管可由一種高分子材料、一種複合材料、一個金屬 材料或是一種合金材料來製成。譬如說，該套管可 由’但不限於由，聚亞醯胺（p〇lyimide)、聚醚醚酮 (polyetheretherketone，PEEK)或不絲鋼來製成 。有利的是，該套管14之末梢16有一開口面積為大於 2%者。更有利的是，該套管14之末梢16之開口面積 為介於2%至50%者。依據本發明，這樣的開口面積 可使該注射導管1發揮最優良之使用效果。該穿孔元 件12俱備充份的剛性而可剌入基質8且發揮最大之藥劑 注入效果。該套管14之末梢16之開口面積因此可大於 20% ，有利的是為介於2%至5〇%者。依據本發明這 樣的設計，該輸導元件可使藥劑在基質令發揮最優良 之散钸效果。 .... ... ..： ：：........Made from Polyimide, p〇iyetheretherketone (PEEK) or stainless steel. Advantageously, the distal end 16 of the sleeve 14 has an open area of greater than 2%. The term "opening area" means the percentage of the total area of the plurality of openings 6 to the total area of the distal end of the sleeve 14. According to the present invention, such an opening area allows the injection catheter to exert the best use effect. More advantageously, the opening 16 of the sleeve 14 has an open area of between 2% and 5%. The perforating member 12 is still sufficiently rigid to break into the substrate 8 and maximize the drug injection effect. The open area of the tip 16 of the sleeve 14 can therefore be greater than 20%, advantageously between 2% and up to. In essence, the present invention sets the β-conducting element 2 to set a sleeve 14 to a 099113627. Form No. A0101 Page /Page/Total 30 Page 0993231107-0 201043284 [0023] 穿孔 [0024] ο Perforating element 12 On the periphery, this can compensate for the shortcomings of insufficient rigidity when the opening of one of the conducting elements is greater than 20%. According to an advantageous embodiment, the plurality of openings 6 can be evenly distributed over the distal end 16 of the sleeve 14. Alternatively, the plurality of openings may be randomly placed on the distal end 16 of the sleeve 14 of the delivery element 2. The plurality of openings 6 are "evenly" distributed over at least one edge of the distal end 16 of the sleeve 14, each opening 6 being equidistant from the opening adjacent thereto. Alternatively, the plurality of openings 6 are "evenly" distributed over the entire perimeter of one of the ends 16 of the sleeve 14 and are equally spaced from the adjacent opening. Another option is that the "evenly" distribution of the plurality of openings 6 means that each of the openings 6 is equidistant in the direction toward the distal end or in the lateral direction thereof adjacent to the opening thereof. In an advantageous embodiment, the injection catheter 1 includes at least one mechanism for controlling the depth of penetration of the delivery element 2 into the substrate 8. The presence of a mechanism for controlling the penetration depth of the transport element into the matrix prevents the risk associated with piercing the substrate. Thus, the presence of the mechanism for controlling the penetration depth of the transport element into the substrate can be such that the penetration depth of the control transport element 2 into the substrate is between 25% and 75% of the thickness of the substrate. The medicament, for this reason, can be injected into the matrix in complete safety. In particular, the means for controlling the penetration depth of the transport element into the substrate may be a tube function element having a memory function, a component configured with a stop design or a component detectable by ultrasonic technology. 099113627 Form No. 1010101 Page 11/Total 30 Page 0993231107-0 [0025] [0027] [0027] [0027] Advantageously, the means for controlling the penetration depth may be a bending element that does not have a force. In particular, the bending member having the memory function is the guiding member 2, the latter comprising at least one sleeve 14 and a perforating member 12, the 14 sleeve being disposed outside the perforating member 〖2, And at least a plurality of openings 6 are formed on at least one side of the distal end 16. For this reason, the depth at which the curved conducting member 2 penetrates into the matrix 8 is controlled by the curvature of the perforating member 12. The curvature of the curved perforating element 12 is defined as the central axis of the longitudinal strip when the injection catheter has been positioned onto the substrate, and the perforated element is positioned after the curved perforating element 12 has been positioned into the substrate. Among the 12 The angle formed by the axis 'both'. Advantageously, the angle is designed to be between 6 〇 2 and 丨, and it is more advantageous to set the angle between -80 and i20e. In particular, the angle can be designed to be between 85. And 1〇〇. between. Alternatively, the machine for controlling the penetration depth may be an element configured with a stop design. <Therefore, the m-memory functioning element is the guiding element 2, the latter comprising at least one sleeve μ and a perforating element 12, the 14 sleeve being disposed outside the perforating element 12, And at least a plurality of openings 6 are formed on at least one of its sides. Thus the conductor element can be configured with a stop design at its proximal end to limit its penetration into the substrate. Another way is to use a component that can be detected by ultrasonic technology as a means of controlling the penetration depth of the conductor. In particular, the component that can be detected by the ultrasonic technology is the transmission component 099113627 Form No. A0101, page 12/total 30 page 0993231107-0 [0028] 201043284, which comprises at least one sleeve 14 and one perforating element 1 2 The sleeve is disposed on the outer circumference of the perforating member, and includes at least a plurality of openings 6 on at least one side of the distal end thereof. [0029] The injection catheter can be provided with a pump to control the injection of the medicament. The pressure. Ο With this pump, a constant pressure can be maintained at the proximal end of the injection catheter. Maintaining a constant pressure during injection and a plurality of openings 6 in the distal end 16 of the wheel guide member 2 provide a controlled distribution of the medicament, which reduces, limits, or even eliminates the risk of edema occurring at the injection site area. In addition, the flow rate of the agent in the catheter is not too high. Thus, in accordance with an advantageous embodiment of the invention, the flow rate of the medicament in the catheter can be less than 6 ml per minute. Advantageously, the flow rate of the medicament in the catheter is less than 3 ml per minute. [0030] Ο In response to the conventional technical disadvantages of the foregoing second item, the method of introducing a medicament into a substrate through an injection catheter of the present invention is produced, that is: I w ~ positioning the distal tip of the injection catheter To the surface of the substrate, the sliding element is used to push the delivery element 2 of the injection catheter 1, the latter comprising at least one perforating element 12 and a sleeve 14, which is disposed outside the perforating element 12 And within the single or plurality of inner tubes 1 of the injection catheter 1, comprising at least a plurality of openings 6 on at least one side of the distal end 16 thereof, and piercing the perforating member 12 into the substrate 8, And pushing the sleeve 12 disposed outside the perforating member 12 in a manner of sliding 099113627 Form No. A0101, page 13 / total. 30 pages 0993231107-0 201043284, - withdrawing the perforating member 12 from the substrate 8, and - placing the medicament Injection into the substrate 8 through the sleeve 14. [0033] According to an advantageous embodiment, the injection catheter can be equipped with a pump to control the injection pressure of the medicament. With this pump, a constant pressure can be maintained on the tip 16 of the transport element 2. According to an advantageous embodiment of the invention, the pressure of the injected medicament at the proximal end of the injection catheter is maintained substantially constant throughout the injection. Maintaining a constant pressure at the time of injection and a controlled distribution of the agent reduces, limits, and even eliminates the risk of edema occurring at the injection site area. In addition, the flow rate of the agent in the catheter is not likely to be too high. Thus, in accordance with an advantageous embodiment of the invention, the flow rate of the medicament in the catheter can be less than 6 ml per minute, and advantageously, the flow rate of the medicament in the catheter can be less than 3 ml per minute. According to another advantageous embodiment of the invention, the time for injecting a 1.0 ml dose of the medicament is from 20 seconds to 3 minutes. According to another advantageous embodiment of the invention, the method of the invention may also comprise a step of controlling the depth of penetration of the transport element 2 into the substrate 8. Advantageously, it penetrates into the substrate 8 to a depth of between 25% and 75% of the thickness of the substrate. The presence of a mechanism to control the penetration depth into the matrix prevents the risk associated with piercing the substrate 8. The medicament, for this reason, can be injected into the matrix in complete safety. According to an advantageous embodiment, the sleeve used in the method of the invention 099113627 Form No. A0101 Page 14 of 30 201043284 14 can comprise at least a plurality of openings 6 . Advantageously, the area of the plurality of openings 6 is designed to be between 0.001 mm2 and 2.0 mm2. Advantageously, the area of the plurality of openings 6 is designed to be between 0.001 mm2 and 2.0 mm2. The total area of the plurality of openings 6 in the distal end 16 of the sleeve 14 can be between 0.002 mm2 and 3.0 mm2. More advantageously, the total area of the plurality of openings 6 on the tip 16 is between 0.2 mm 2 and 3.0 mm 2 , and most advantageously, the total area of the plurality of openings 6 on the tip 4 is between 0.3 mm 2 and 2.0 mm 2 . between. The area of these openings 6 provides for a uniform distribution of the agent in the matrix which aids in the dispersion within the matrix to avoid edema at the injection site. [0035] According to another advantageous embodiment, the plurality of openings 6 may be of different shapes such as an egg shape, a square shape, a circular shape, a rectangular shape, a triangular shape, an elliptical shape or a shape such as a cut or a rhomboid. , 蜷-like or spiral-like. The plurality of openings 6 can be disposed on all surfaces of the distal end 16 of the conducting element 14. The plurality of openings 6 allow the medicament to be injected into the substrate 8 in a controlled manner. The perforating element 12 is used to pierce the substrate 8 and guide the movement of the sleeve 14 within the substrate 8. The perforating element 12 can be a hollow needle or wire. The perforating element 12 can include at least one prong to facilitate its intrusion into the substrate 8. The perforating member 12 can be made of a material having a shape memory capability. The material having the shape memory ability can be an alloy of titanium, a copper base or an iron base alloy. Advantageously, the shape memory capable material is a nickel and titanium 099113627 Form No. A0101 Page 15 of 30 0993231107-0 201043284 Alloy, for example, NiTINOL (Nitinol). The alloy of nickel and titanium may also contain a small amount of copper, iron, niobium, palladium or platinum. The sleeve can be made of a polymer material, a composite material, a metal material or an alloy material. For example, the sleeve can be made of, but not limited to, polypether (polyetheretherketone, PEEK) or non-filament steel. Advantageously, the distal end 16 of the sleeve 14 has an open area of greater than 2%. More advantageously, the distal end 16 of the sleeve 14 has an open area of between 2% and 50%. According to the present invention, such an opening area allows the injection catheter 1 to exert the most excellent use effect. The perforating element 12 is sufficiently rigid to break into the substrate 8 and maximize the drug injection effect. The open area of the tip 16 of the sleeve 14 can therefore be greater than 20%, advantageously between 2% and 5%. In accordance with such a design of the present invention, the delivery element allows the agent to exert the best diathering effect on the substrate. .... ... ..: ::........
[0037] 依據一種有利的實施例，該複數個開口 6 ▼以均勻分 配在該套营14之末梢16上。 另一種選項是，該複數簡σ可以隨機地設置於該輸 導元件2之套管14之末梢16上。該複數個開口 6 「均勻地」分佈於該套管14之末梢16之至少一個邊上， 其每一個開口6皆與其鄰近之開口成等距者。該複數個開 口 6「均勻地」分佈於該套管14之末梢此—段之全週邊 上’其每-個開口6皆與其鄰近之開口成等距者。該複 數個開d 6 「均勻地」分佈係指其每—個開口 6皆在 099113627 表單編號Α0101 第16頁/共30頁 0993231107-0 201043284 往末梢端方向上、或在其橫向方向上與其鄰近之開口成 等距者。 ^)38]依據本發明之方法，冑輸導元件2刺人到該基質8 中的冰度，就是可以得到控制的。有利的是，其刺入 該基質中之深度為介於該基質厚度之25%至75%者。因 此控制進入到基質中之刺入深度之機制之存在，可以 防止刺穿該基質8之相關風險之發生。該藥劑可以因此 之故，在完全安全的情況下被注射到該基質之中。依據 〇 纟發明之方法’可以增加一個步驟那就是控制該輸導元 件刺入到該基質中的深度。 闕尤其’馳制輸導元件2冑人到基質8中之刺入深 度，可以是由一個俱有記憶功能之彎曲元件、一個配 置有止動設計之7C件或是—個可被超音波雜偵知之元 件所控制者。依據本發明之另一項有利之實施例，可 以用一個俱有記憶功能之彎曲元件來控制該輸導元件2刺 — .? 入基質8中之深度者。尤其是，筚俱有記憶功能之彎曲 Ο 元件為該輸導元件之，後者至少包含一個套管14以及一 個穿孔疋件12,該14套管為設置在該穿孔元件12之 外週者，以及其至少包含複數個開口6於其末梢丨6之至少 一個侧面上者。因此之故，該彎曲的輸導元件2刺入到該 基質8中的深度，就是由該穿孔元件12的彎曲度來控制 的。有利的是，該穿孔元件12在基質8内有彎曲形狀者。 該彎曲的穿孔元件12的彎曲度是定義為，當該注射導 官已定位到基質8上時之其長方向上之中心軸線，與當 該彎曲的穿孔元件12進入到基質中就定位後該穿孔元 099113627 表單編號A0101 第Π頁/共30頁 0993231107-0 201043284 件12之中心軸線，兩者間所形成之夾角。 有利的是，將該夾角設計成介於6〇 q及12〇2之間 ’而尤其以將該夾角設計成介於8〇 2及120Q之間 更為有利。尤其可以將該夹角設計成介於85。及1〇〇。 之間。 [0040] [0041] 依據本發明之另一項有利之實施例，可以用一個配置 有止動設計之元件，來控制該輸導元件2刺入基質8 中之深度者。尤其是，該俱有記憶功能之彎曲元件為 該輸導元件2,後者至少包含—個套管14以及一個穿 孔元件12,該14套管為設置在該穿孔元件12之外週 者，以及其至少包含複數個德口6於其末梢16之至少一個 侧面上者。因此，該輸導元件可以在它的近端點配置一 個止動設計來限制其刺入到基質中之深度。 依據本發明之另一項有利之實施例，可以用一個可被 超音波技術來偵知之元件來控制該輸導元件刺入基質中 之深度者。尤其是，該可被超音波技術偵知之元件 即為该輸導元件’其至少包合一個.套管14以及一個 穿孔元件12 ，該套管為設置在該穿孔元件之外週者， 以及其至少包含複數個開口 6於其末梢16之至少一個侧面 上者。 [0042] 針對改進前述第三項之習知技藝缺點，本發明完成了 應用注射導管將藥劑引入一種基質之新方法。依據本發 明一項有利的實施例，基質可為—器官。有利的是， 該基質可以是心肌、肝臟、腎、胰腺、脊髓或是腦。 更有利的是’該基質為心肌。依據本發明之一個有 099113627 表單編號A0101 第18頁/共30頁 0993231107-0 201043284 利的實施例’該藥劑可以為一種對該基質有療效之液體 。譬如說’該藥劑可以是，但不限於只是，-個含有細 胞或大粒分子如蛋白質之液體，譬如說，生長荷爾蒙、 藥、自然或合成之微米或奈米粒子者。 譬如說’用來作藥劑之細胞其直徑介於1〇至6〇岬 之間。另一方面，藥劑可為本產業中之任何製劑。有 利的是，該藥劑是-個含有自幹細胞滋生出來之細胞之 溶劑。 實施例 Ο [0043] 此處所使用之名詞及描述語都只是用來作說明用途者， 其不可視為_本發明之範圍者。4本技術領域中具有 通常知識者都會知道應用本新發明之精神及其申請專利 範圍可以推演出無數之變化；因此此處所使用之名詞 ，在未作特殊聲明時，都應以最廣意之方式來理解 例1 〇 [0044] 圖2顯示一個依照本番明的一個售別實施例而實施出的 輸導元件2，其至少包含一個套管14及一個穿孔元件 12 。該套管14之末梢16上，至少設有複數個切 口形狀之開口 6 。複數個開口 6有完全相同之面積。 該套管14係由聚亞醯胺（p〇iyimide)來製成。 該穿孔元件12可為一個由鎳鈦鎳鈦諾（Nitinol)來製 成之空心之針具。利用注射導管1來將一種藥劑引入— 種基質8,該注射導管1需先置於基質8之表面。該輸導 元件係先置於基質8之表面，穿孔元件12再刺入基質8申 099113627 表單编號A0101 第19頁/共30頁 0993231107-0 201043284 。將該一個穿孔元件12刺入後，該套管以滑動方式推 進於穿孔元件12外方，該穿孔元件12此處便是空心 之針具。當套管14及穿孔元件12就定位後，該穿孔元件 12又會被從基質8中抽回，讓藥劑此時可以注入基質8中 。該藥劑通過了空心針具，也就是穿孔元件12，自基 質8外，流過套管14進入到基質8内。 例2 [0045] [0046] 圖3顯示一個依照本發明的一個特別實施例而實施出的 輸導元件2之示意圖，其至少包含一個套管14及一個穿孔 元件12 〇 該套管14之末梢16上，至少設有複數個斜置之 長方形狀開口 6 。該套管係由聚醚越酮（poly- etheretherketone，PEEK)來製成。該穿孔元件 12為一個由鎳鈦諾（Nitino 1)來製成之空心之針具。 利用注射導管1來將一種藥劑引入一種基質8，該注射導 si需先置於基質8之表面。該輸導元件係先置於基質8 之表面，穿孔元件12再刺入基質8中。將該一個穿孔元 件12刺入後，該套管以滑動方式於穿孔元件12外方作 推進，該牙孔元件12此處便是空心之針具。當套管μ 及穿孔元件12就定位後，該穿孔元件12又會被從基質8中 抽回，讓藥劑此時可以注入基質8中。該藥劑自基質8外 通過了空心針具，也就是穿孔元件12，流過套管14進 入到基質8内。 例3 圖4A及4B顯示一個依照本發明而實施出的特殊實施 099113627 表單編號A0101 第20頁/共30頁 0993231107-0 201043284 例之注射導管在其末稍部位的剖面示意圖。該注射導 官1至少包含一個内管10以及一個輸導元件2 。 該輪導元件至少包含一個穿孔元件丨2以及一個套管14。 該套管14之末梢端區中有複數個開口 6 。該穿孔元 件12為由鎳鈦諾（Nitin〇i)來製成之金屬線。該套管 14至少包含二個内管a及β而有一交接點c。套管14上 在乂接點C以外在往末梢端方向的一段不被置入基質中 。该穿孔元件12及該套管14係藏置於注射導管中 ，直到注射導管1被定位到基質8上為止。待該 注射導管1被定位到基質8之表面後，穿孔元件12才 再刺入基質8之中《將該‘個穿孔元件12在基質8内就 定位後，該套管14便以滑動方式於穿孔元件12外方被 推行前進，見圖4Α。當套管14及穿孔元件12就定位後， 該穿孔元件12又會從基質8中被抽回，留於套管14之交 接點C以外之内管Β中。此時藥劑便可通過内管a注射到基 質8中。 二… 1^.. 例4 Ο 〃 * [0047]圖5示出一張圖表，顯示微在一個基質中之停留 率。微米球由二個不同的注射導管來作注射。第一個 注射導管B是Myostar ®輸導器，其包含有一個輸導元 件，一個直的空心針具其，只有在其末梢處有一開口。 注射導管A係一個依照本發明而實施出的例子。該注射導 管入至少包含一個套管以及一個穿孔元件，作為輸送元件 。#亥套管為由聚亞醯胺（Polyimide)來製成，而 穿孔元件為由錄鈇錄鈦謹（Nitino 1)來製成。今套 099113627 表單編號A0101 第21貢/共30頁 0993231107-0 201043284 管之末梢上，至少設有七個面積相同之切口形狀之開口 6 。該套管開口面積係大於2%。該穿孔元件為彎曲狀 者。該内管中心軸線，與經過該末梢開口之中心之軸線 兩者間所形成之夾角約為90s 。 [0048] [0049] 本實驗系列係在活體之外的豬心肌組織上所進行者。該 心臟係架在PhysioHeat (製造者：Hem〇Lab， Eindhoven, Netherlands)裝置上，使其接受含氧 及葡萄糖之供血而繼續存活並且可以在數小時之内維持 正常心跳（每分鐘跳80至11〇下）。注射導 管之末梢被定位到基質之外方’然後注射導管之輸導元 件便以滑動方式於内管内被推行並刺入基質8中。注射_ 種微米球之液體。此微米球之液體便被當成一個本系 列實驗中之標準藥劑。此微米球之液想（lml中含有 2.5百萬微米球）被用來以一個定速率注射2〇秒。該停 留率係依據所使甩不同注射導管在每丨8基質中微米球停 留之數目（/1〇3)。此處街使用之镟米球為直徑為1 5 μηι之塑膠球。 使用β示出一張圖表，顯示微米球在一個基質中之停留 率為每1 g基質中不超過11. 103個。使用該停留率 為每1 g基質中微米球停留之數目為19.1〇3。藥劑在基 質令之停留率在獨立之組織實驗中以大於10¾之數據而有 改進。 【圖式簡單說明】 圖1A顯示一個依照本發明的一個特別實施例而實施出的 注射導管的例子的示意圖。 099113627 表單編號A0101 第22頁/共30頁 0993231107-0 [0050] 201043284 [0051] Ο 圖1Β顯示一個依照本發明的一個實扩幻 元件的套管的剖面圖。 圖2顯示一個依照本發明的—個 、_ 別實施例而實施出的 輸導元件’其至少包含一個套瞢 b及一個穿孔元件。 圖3顯示另-個依照本發明的—個特別實施例而實施出 的輸導元件，其至少包含-個套管及-個穿孔元件。 圖4A顯不一個依照本發明的—個特別實施例而實施出的 注射導管正在作穿孔時的剖面示意圖。 [0055] 圖4B顯示一個依照本發明的一個實施例而實施出的該相 同注射導管正在作穿孔時的片段剖面示意圖β [0056] 圖5示出一張圖表，顯示微米球,（mi.cr0Sphere)在一 個心臟注射點處之停留率。該微米球係以不同種類之醫 用器材來作注射者。 而實施出的輸導 [0052] [0053] [0054] ο 【主要元件符號說明】 [0057] 1注射導管 2輸導元件 6開口 8基質 10内管 12穿孔元件 14套管 16套管末梢 18開口之外表面 2 0開口之内表面 099113627 表單編號A0101 第23頁/共30頁 0993231107-0 201043284 22套管末梢開口 099113627 表單編號A0101 第24頁/共30頁 0993231107-0[0037] According to an advantageous embodiment, the plurality of openings 6 ▼ are evenly distributed on the tip 16 of the camp 14. Alternatively, the complex sigma σ can be randomly placed on the distal end 16 of the cannula 14 of the delivery element 2. The plurality of openings 6 are "evenly" distributed over at least one edge of the distal end 16 of the sleeve 14, each opening 6 being equidistant from the opening adjacent thereto. The plurality of openings 6 are "evenly" distributed over the entire periphery of the end of the sleeve 14 and each of the openings 6 are equidistant from the opening adjacent thereto. The plurality of open d 6 "evenly" distributions means that each of the openings 6 is at 099113627 Form No. 1010101 Page 16 / Total 30 Page 0993231107-0 201043284 To the distal end or adjacent to it in the lateral direction The openings are equidistant. ^) 38] According to the method of the present invention, the ice density of the crucible transport element 2 into the substrate 8 can be controlled. Advantageously, the depth of penetration into the matrix is between 25% and 75% of the thickness of the substrate. Thus, the presence of a mechanism to control the penetration depth into the matrix prevents the risk associated with piercing the substrate 8 from occurring. The agent can thus be injected into the matrix under complete safety. According to the method of the invention, a step can be added to control the depth of penetration of the conductor element into the substrate.阙 In particular, the penetration depth of the 'transducing component 2' into the substrate 8 can be a bending element with a memory function, a 7C piece with a stop design, or a supersonic wave. The person controlled by the component of the detection. According to another advantageous embodiment of the invention, a bending element having a memory function can be used to control the depth of the guiding element 2 into the substrate 8. In particular, the flexing element having a memory function is the guiding element, the latter comprising at least one sleeve 14 and a perforating element 12, which is disposed outside the perforating element 12, and It comprises at least a plurality of openings 6 on at least one side of its distal end 6 . For this reason, the depth at which the curved conducting member 2 penetrates into the substrate 8 is controlled by the curvature of the perforating member 12. Advantageously, the perforating element 12 has a curved shape within the substrate 8. The curvature of the curved perforating element 12 is defined as the central axis in the longitudinal direction of the injection guide when it has been positioned onto the substrate 8, and after positioning of the curved perforating element 12 into the substrate Perforation element 099113627 Form No. A0101 Page/Total 30 Page 0993231107-0 201043284 The central axis of the piece 12, the angle formed between the two. Advantageously, the angle is designed to be between 6 〇 q and 12 〇 2 and it is particularly advantageous to design the included angle to be between 8 〇 2 and 120 。. In particular, the angle can be designed to be between 85. And 1〇〇. between. [0041] According to another advantageous embodiment of the invention, an element configured with a stop design can be used to control the depth of penetration of the transport element 2 into the substrate 8. In particular, the bending element having a memory function is the guiding element 2, the latter comprising at least a sleeve 14 and a perforating element 12, the 14 sleeve being disposed outside the perforating element 12, and At least a plurality of ports 6 are included on at least one side of the distal end 16. Thus, the conducting element can be configured with a stop design at its proximal end to limit its penetration into the substrate. In accordance with another advantageous embodiment of the present invention, an element that can be detected by ultrasonic techniques can be used to control the depth of penetration of the conductive element into the substrate. In particular, the component that can be detected by the ultrasonic technology is the conductive component 'which contains at least one. The sleeve 14 and a perforating element 12, which is disposed outside the perforating element, and At least a plurality of openings 6 are included on at least one side of the distal end 16. [0042] In response to the conventional technical disadvantages of the foregoing third item, the present invention accomplishes a new method of introducing an agent into a substrate using an injection catheter. According to an advantageous embodiment of the invention, the substrate can be an organ. Advantageously, the matrix can be myocardium, liver, kidney, pancreas, spinal cord or brain. More advantageously, the matrix is a myocardium. According to one of the inventions there is 099113627 Form No. A0101 Page 18 of 30 0993231107-0 201043284 Example of the invention The agent may be a liquid which is effective against the substrate. For example, the agent may be, but is not limited to, only a liquid containing cells or large molecules such as proteins, such as growth hormones, drugs, natural or synthetic micro or nano particles. For example, the cells used for medicinal purposes range in diameter from 1〇 to 6〇岬. In another aspect, the agent can be any formulation in the industry. Advantageously, the agent is a solvent containing cells derived from stem cells. EXAMPLES [0043] The nouns and descriptors used herein are used for illustrative purposes only and are not to be construed as limiting. 4 Those of ordinary skill in the art will know that the spirit of applying this new invention and the scope of the patent application can be used to innumerable changes; therefore, the nouns used herein should be the most widely used without special declaration. Means to Understand Example 1 [0044] FIG. 2 shows a transport element 2 implemented in accordance with a preferred embodiment of the present invention, comprising at least one sleeve 14 and one perforated element 12. At least a plurality of slit-shaped openings 6 are formed in the distal end 16 of the sleeve 14. The plurality of openings 6 have exactly the same area. The sleeve 14 is made of polyamidimide. The perforating member 12 can be a hollow needle made of Nitinol. The injection catheter 1 is used to introduce an agent into the substrate 8, which is placed first on the surface of the substrate 8. The transport element is placed first on the surface of the substrate 8, and the perforated element 12 is then pierced into the substrate 8 099113627 Form No. A0101 Page 19 of 30 0993231107-0 201043284. After piercing the one perforating element 12, the sleeve is slidably pushed out of the perforating element 12, which is here a hollow needle. When the sleeve 14 and the perforating member 12 are positioned, the perforating member 12 is again withdrawn from the substrate 8 so that the medicament can be injected into the substrate 8 at this time. The medicament passes through the hollow needle, i.e., the perforating member 12, from the substrate 8, through the sleeve 14, into the substrate 8. Example 2 [0046] FIG. 3 shows a schematic view of a transport element 2 implemented in accordance with a particular embodiment of the present invention, comprising at least one sleeve 14 and a perforated element 12, the distal end of the sleeve 14. At least 16, a plurality of obliquely-shaped rectangular openings 6 are provided. The sleeve is made of poly-etheretherketone (PEEK). The perforating member 12 is a hollow needle made of Nitinol. The injection catheter 1 is used to introduce an agent into a substrate 8, which is placed on the surface of the substrate 8. The transport element is placed first on the surface of the substrate 8, and the perforated element 12 is then pierced into the substrate 8. After piercing the perforating element 12, the sleeve is advanced in a sliding manner outside the perforating element 12, which is here a hollow needle. When the sleeve μ and the perforating element 12 are positioned, the perforating element 12 is again withdrawn from the substrate 8 so that the medicament can be injected into the substrate 8 at this time. The medicament passes from the outside of the substrate 8 through a hollow needle, i.e., a perforating member 12, which flows through the sleeve 14 into the substrate 8. Example 3 Figures 4A and 4B show a special implementation implemented in accordance with the present invention. 099113627 Form No. A0101 Page 20 of 30 0993231107-0 201043284 A schematic cross-sectional view of an injection catheter in its distal portion. The injection guide 1 comprises at least one inner tube 10 and one transport element 2. The wheel guide element comprises at least one perforating element 丨2 and a sleeve 14. The sleeve 14 has a plurality of openings 6 in the distal end region. The perforating member 12 is a metal wire made of Nitinium. The sleeve 14 includes at least two inner tubes a and β and a junction c. A section of the sleeve 14 outside the nip point C in the direction toward the distal end is not placed in the substrate. The perforating element 12 and the cannula 14 are tethered into the injection catheter until the injection catheter 1 is positioned over the substrate 8. After the injection catheter 1 is positioned on the surface of the substrate 8, the perforating element 12 is again pierced into the substrate 8. Once the perforating element 12 is positioned within the substrate 8, the sleeve 14 is slidably The outer side of the perforating element 12 is pushed forward, see Figure 4Α. When the sleeve 14 and the perforating element 12 are positioned, the perforating element 12 is again withdrawn from the substrate 8 and remains in the inner tube other than the junction C of the sleeve 14. At this point, the medicament can be injected into the matrix 8 through the inner tube a. 2... 1^.. Example 4 Ο 〃 * [0047] Figure 5 shows a graph showing the residence rate of micro in a matrix. The microspheres are injected by two different injection catheters. The first injection catheter B is a Myostar® transducer that contains a transducer element, a straight hollow needle with an opening only at its distal end. Injection Catheter A is an example implemented in accordance with the present invention. The injection catheter contains at least one cannula and a perforating element as a delivery element. The #海 casing is made of Polyimide, and the perforated element is made of Nitino 1. Present set 099113627 Form No. A0101 No. 21 tribute / Total 30 pages 0993231107-0 201043284 There are at least seven openings with the same slit shape on the tip of the tube. The casing opening area is greater than 2%. The perforating element is curved. The angle between the central axis of the inner tube and the axis passing through the center of the distal opening is about 90 s. [0049] This experimental series was performed on porcine myocardial tissue outside the living body. The heart is placed on a PhysioHeat (manufacturer: Hem〇Lab, Eindhoven, Netherlands) device to continue to survive the blood supply of oxygen and glucose and maintain a normal heartbeat within a few hours (80 to 11 per minute) Your Majesty). The distal end of the injection catheter is positioned outside of the substrate' and the delivery element of the injection catheter is then slidably pushed into the inner tube and penetrated into the substrate 8. Injection _ microspheres of liquid. This microsphere liquid is considered a standard agent in this series of experiments. This microsphere solution (2.5 ml microspheres in 1 ml) was used to inject at a constant rate for 2 sec. The retention rate is based on the number of microspheres (/1 〇 3) that each of the different injection catheters has in each of the 8 matrixes. The glutinous rice balls used in the street here are plastic balls with a diameter of 15 μm. A graph is shown using β, showing that the retention rate of the microspheres in a matrix is no more than 11.103 per 1 g of matrix. The residence rate was used to be 19.1 〇 3 for the number of microspheres per 1 g of matrix. The retention rate of the agent in the matrix was improved in an independent tissue experiment with data greater than 103⁄4. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1A shows a schematic diagram of an example of an injection catheter implemented in accordance with a particular embodiment of the present invention. 099113627 Form No. A0101 Page 22 of 30 0993231107-0 [0050] FIG. 1A shows a cross-sectional view of a sleeve of a real expansion element in accordance with the present invention. Fig. 2 shows a conducting element 'consisting of at least one set b and one perforating element implemented in accordance with an embodiment of the invention. Figure 3 shows another embodiment of a conducting element implemented in accordance with a particular embodiment of the present invention comprising at least one sleeve and one perforating element. Figure 4A shows a schematic cross-sectional view of a syringe catheter being made in accordance with a particular embodiment of the present invention as it is being perforated. 4B shows a cross-sectional view of a fragment of the same injection catheter being perforated in accordance with an embodiment of the present invention. [0056] FIG. 5 shows a graph showing a microsphere, (mi.cr0Sphere) The retention rate at a heart injection point. The microspheres are used as injectors for different types of medical equipment. And the implemented transmission [0052] [0051] [Main component symbol description] [0057] 1 injection catheter 2 conduction element 6 opening 8 matrix 10 inner tube 12 perforation element 14 sleeve 16 sleeve end 18 Opening surface 2 0 opening inner surface 099113627 Form No. A0101 Page 23 / Total 30 Page 0993231107-0 201043284 22 Sleeve End Opening 099113627 Form No. A0101 Page 24 / Total 30 Page 0993231107-0