TWI675673B - Biofilm removal system - Google Patents
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Abstract
本發明揭露一種生物膜清除系統,應用於去除腔體內之生物膜。生物膜清除系統包含有載體與清除設備。載體包含有奈米磁珠、抑菌物質、以及包覆抑菌物質與奈米磁珠之外膜。清除設備包含有磁控組件與振動組件。磁控組件用以引導奈米磁珠帶動載體接近生物膜。振動組件用以產生振動並聚焦至生物膜,而產生微氣泡使生物膜之至少一部份脫離內腔壁,並且破壞外膜而釋放抑菌物質。本發明用振動組件剝離下大部分的生物膜,同時使載體釋放抑菌物質以抑制剩餘的細菌,達到高效率的精準治療。 The invention discloses a biofilm removal system, which is applied to remove a biofilm in a cavity. The biofilm removal system includes a carrier and a removal device. The carrier includes nanometer magnetic beads, bacteriostatic substance, and an outer film covering the bacteriostatic substance and nanometer magnetic beads. The cleaning device includes a magnetron component and a vibration component. The magnetic control component is used to guide the nanometer magnetic beads to drive the carrier to approach the biofilm. The vibration component is used to generate vibration and focus on the biofilm, while generating micro-bubbles makes at least a part of the biofilm detach from the inner cavity wall, and destroys the outer membrane to release bacteriostatic substances. The invention uses a vibration component to peel off most of the biofilm, and at the same time causes the carrier to release a bacteriostatic substance to suppress the remaining bacteria, thereby achieving high-efficiency and precise treatment.
Description
一種清除生物膜的系統,尤其指一種利用振動與磁力以清除腔體內生物膜的系統。 A system for removing biofilm, especially a system for removing biofilm in cavity using vibration and magnetic force.
隨著醫學的進步,越來越多的管路及人工植入物被使用於醫療及改善人類的生活。然而,在獲得這些醫療輔助所帶來的好處的同時,感染的問題卻是個難以避免及棘手的問題。尤其是細菌感染常會造成併發症及後遺症,甚至嚴重到發生敗血症,因此對於細菌感染的預防及治療是當前醫學所致力研究之方向。尤其,泌尿道感染的機率就占醫療相關感染約40%。而且當導尿管留置於人體體內的時間每增加1天,菌尿發生率就會增加3%~10%。因此,有效去除膀胱的細菌感染是為當前必須改善之課題。 With the advancement of medicine, more and more tubing and artificial implants are being used for medical treatment and improving human life. However, while receiving the benefits of these medical aids, the problem of infection is an unavoidable and difficult problem. In particular, bacterial infections often cause complications and sequelae, and even serious enough to cause sepsis. Therefore, the prevention and treatment of bacterial infections is the research direction of current medical research. In particular, urinary tract infections account for about 40% of medically related infections. And each time the urinary catheter is left in the body, the incidence of bacteriuria will increase by 3% to 10%. Therefore, the effective removal of bacterial infections in the bladder is a problem that must be improved at present.
要解決細菌感染的問題,就必須先解決生物膜的形成,因為形成生物膜係為微生物的生存策略。生物膜是由微生物以及微生物所分泌之胞外物質附著在物體表面所形成的結構,換句話說,生物膜就是一堆微生物形成的社群。成群生長的主要目的就是為了抵禦外在環境所帶來的壓力,如:營養的缺乏、酸鹼值、極端溫度、或甚至是去汙劑或抗生素所帶來的威脅。 To solve the problem of bacterial infection, the formation of biofilms must be solved first, because the formation of biofilms is a survival strategy for microorganisms. A biofilm is a structure formed by the attachment of microorganisms and extracellular substances secreted by microorganisms to the surface of an object. In other words, a biofilm is a community of microorganisms. The main purpose of group growth is to resist the pressure brought by the external environment, such as: nutritional deficiency, pH value, extreme temperature, or even the threat of detergents or antibiotics.
對於去除形成於人體體內的生物膜,在目前醫療上的方法多為直接對生物膜進行渦旋、刮擦、沖洗、刷洗的物理性治療或以抗生素或 藥劑的生化性治療。然而,抗生素治療的共識是必要時劑量越低越好,以減少細菌產生抗藥性的風險。更重要的是,使用習知的方式進行生物膜去除時非常容易傷害到正常的組織與細胞。因此,目前亟需一種能落實精準醫療,抑制生物膜形成的技術。 For the removal of biofilms formed in the human body, the current medical methods are mostly physical treatments such as direct vortexing, scraping, rinsing, and scrubbing of biofilms or antibiotics or Biochemical treatment of medicaments. However, the consensus in antibiotic treatment is that the lower the dose, the better, if necessary, to reduce the risk of bacteria developing resistance. More importantly, it is very easy to damage normal tissues and cells when removing biofilms using conventional methods. Therefore, there is an urgent need for a technology that can implement precision medicine and inhibit biofilm formation.
有鑑於此,本發明揭露一種生物膜清除系統,係應用於去除一腔體內之一內腔壁上之生物膜。腔體內還容置有液體。該生物膜清除系統包含有一載體與一清除設備。載體位於腔體內且包含有一奈米磁珠、用以針對性地抑制生物膜之抑菌物質、以及包覆抑菌物質與奈米磁珠之熱敏脂膜。清除設備位於該腔體外且包含有一磁控組件與一振動組件。磁控組件用以引導奈米磁珠帶動載體接近生物膜。振動組件用以產生複數個振動並將振動聚焦至生物膜或生物膜外之一限定距離之內,以於液體內產生微氣泡使生物膜之至少一部份脫離內腔壁,並且破壞熱敏脂膜以釋放抑菌物質。 In view of this, the present invention discloses a biofilm removal system, which is applied to remove a biofilm on an inner cavity wall of a cavity. Liquid is also contained in the cavity. The biofilm removal system includes a carrier and a removal device. The carrier is located in the cavity and contains a nano-magnetic bead, a bacteriostatic substance for targeted inhibition of the biofilm, and a heat-sensitive lipid film covering the bacteriostatic substance and the nano-magnetic bead. The removal device is located outside the cavity and includes a magnetron component and a vibration component. The magnetic control component is used to guide the nanometer magnetic beads to drive the carrier to approach the biofilm. The vibration component is used to generate a plurality of vibrations and focus the vibrations within a defined distance of the biofilm or a biofilm, so as to generate micro-bubbles in the liquid to cause at least a part of the biofilm to escape from the inner cavity wall and damage the thermal sensitivity Lipid film to release bacteriostatic substances.
振動組件進一步包含有複數個振動元件。振動元件排列形成相位式陣列。每一振動元件依序產生振動且振動之能量於同一時間抵達生物膜或生物膜外之限定距離之內。 The vibration assembly further includes a plurality of vibration elements. The vibration elements are arranged to form a phased array. Each vibrating element sequentially generates vibration and the energy of the vibration reaches the biofilm or a limited distance outside the biofilm at the same time.
振動組件進一步將振動聚焦至腔體內以使液體產生漩渦或擾流,藉由漩渦或擾流使該生物膜之至少一部份脫離該內腔壁。 The vibration component further focuses the vibration into the cavity to cause the liquid to vortex or turbulence, and at least a part of the biofilm is detached from the inner cavity wall by the vortex or turbulence.
振動組件於腔體內產生的微氣泡於消滅時產生的壓力波作用在該生物膜上,以使生物膜之至少一部份脫離內腔壁。 The pressure wave generated when the micro-bubbles generated by the vibration component in the cavity is destroyed acts on the biofilm, so that at least a part of the biofilm is separated from the inner cavity wall.
振動組件產生之振動之頻率係介於0.3MHz至4.0MHz。 The frequency of the vibration generated by the vibration component is between 0.3 MHz and 4.0 MHz.
磁控組件進一步產生高頻交流磁場,以產生熱能抑制生物膜以及破壞熱敏脂膜以釋放抑菌物質。 The magnetron component further generates a high-frequency AC magnetic field to generate thermal energy to suppress the biofilm and destroy the heat-sensitive lipid film to release bacteriostatic substances.
清除設備進一步包含有一第一探頭,第一探頭包含有前述的磁控組件、振動組件與一磁力遮蔽。磁力遮蔽位於磁控組件與振動組件之間,用以減少磁控組件對振動組件造成的電磁效應。 The removal device further includes a first probe, and the first probe includes the aforementioned magnetron component, vibration component, and a magnetic shield. The magnetic shielding is located between the magnetron component and the vibration component to reduce the electromagnetic effect of the magnetron component on the vibration component.
載體大致為圓形,載體之直徑小於0.22μm。 The carrier is approximately circular, and the diameter of the carrier is less than 0.22 μm.
載體進一步包含有一生物膜配體。生物膜配體之第一端接合於熱敏脂膜外側,生物膜配體之第二端用以接合於生物膜。 The carrier further includes a biofilm ligand. The first end of the biofilm ligand is joined to the outside of the thermosensitive lipid film, and the second end of the biofilm ligand is used to join the biofilm.
生物膜清除系統進一步包含有一第二探頭用以接收回聲,回聲係因振動組件產生之振動或一第二振動源產生之一第二振動觸及該腔體與該生物膜而產生。 The biofilm removal system further includes a second probe for receiving an echo, which is generated by the vibration generated by the vibration component or a second vibration generated by a second vibration source touching the cavity and the biofilm.
本發明之生物膜清除系統提供有多種清除方法,分別進行或是同時進行該些清除方法可以獲得不同之效果。 The biofilm removal system of the present invention provides multiple removal methods, and different effects can be obtained by performing these removal methods separately or simultaneously.
其中一種去除腔體內生物膜的方法是注入載體於該腔體中;利用磁控組件奈米磁珠引導奈米磁珠帶動載體接近生物膜;控制振動組件產生複數個振動,並將這些振動聚焦至生物膜或生物膜外之一限定距離之內;利用這些振動聚焦產生接觸生物膜之複數個微氣泡,以使生物膜之至少一部分脫離內腔壁;同時振動之能量或振動產生的熱能破壞熱敏脂膜以釋放抑菌物質,由於載體靠近生物膜,抑菌物質也會較順利地作用到生物膜內的細菌。 One of the methods to remove the biofilm in the cavity is to inject the carrier into the cavity; the nanomagnetic beads of the magnetic control component are used to guide the nanomagnetic beads to drive the carrier to approach the biofilm; the vibration component is controlled to generate a plurality of vibrations, and the vibrations are focused Within a defined distance from the biofilm or one outside the biofilm; use these vibrations to focus to generate multiple microbubbles that contact the biofilm, so that at least a part of the biofilm is detached from the inner cavity wall; at the same time, the energy of the vibration or the thermal energy generated by the vibration is destroyed The heat-sensitive lipid film releases the bacteriostatic substance. Since the carrier is close to the biofilm, the bacteriostatic substance will also smoothly affect the bacteria in the biofilm.
另外一種去除腔體內生物膜的方法是注入載體於該腔體中;利用載體上的生物膜配體與生物膜產生特異性結合;控制磁控組件產 生高頻交流磁場使得載體內的奈米磁珠產生磁振;磁振產生高於生物體溫的熱能使生物膜內的細菌死亡;載體的熱敏脂膜因為磁振及磁振產生的熱能而被破壞,釋放出其內的抑菌物質。 Another method to remove the biofilm in the cavity is to inject a carrier into the cavity; use the biofilm ligand on the carrier to specifically bind to the biofilm; control the production of the magnetron component The generation of high-frequency AC magnetic field causes the nanometer magnetic beads in the carrier to generate magnetic vibration; the magnetic vibration generates heat energy higher than the biological body temperature to cause the bacteria in the biofilm to die; the thermosensitive lipid film of the carrier is caused by the magnetic vibration and the thermal energy generated by the magnetic vibration Destroyed, releasing bacteriostatic substances inside.
另外一種去除腔體內生物膜的方法包含以下步驟:將振動組件貼近於腔體之對應外表面;控制振動組件產生複數個振動,並將這些振動聚焦至生物膜上;接著,利用這些振動聚焦產生接觸生物膜之複數個微氣泡,以使生物膜之至少一部分脫離內腔壁。 Another method for removing the biofilm in the cavity includes the following steps: close the vibration component to the corresponding outer surface of the cavity; control the vibration component to generate a plurality of vibrations and focus the vibrations on the biofilm; then, use these vibrations to focus and generate The plurality of micro-bubbles are contacted with the biofilm to disengage at least a part of the biofilm from the inner cavity wall.
相較於習知技術,本發明之去除腔體內生物膜的方法可以針對生物體內的生物膜進行去除。利用具有相位式陣列探頭的振動裝置讓生物膜剝落的機理,比起利用物理性清創的手術方式更能將深入到內腔壁上的生物膜清除乾淨。本發明利用具有相位式陣列探頭的振動組件讓生物膜剝落的方法,比起現今的清除方法更不傷害患者之身體組織。本發明利用載體與奈米磁珠乘載藥劑到達生物膜部位,可以使藥劑更精準發揮功效。藉此方法可降低藥劑量,避免傷害組織,也減少身體代謝藥劑的負擔。本發明可直接從放置導尿管的患者體外直接進行,被去除掉的生物膜再經由導尿管排出體外,也可以將設備沿著導尿管進入患者膀胱,更容易掌握振動的聚焦位置。 Compared with the conventional technology, the method for removing the biofilm in the cavity of the present invention can be used to remove the biofilm in the body. The mechanism of using a vibration device with a phased array probe to peel off the biofilm can remove the biofilm deep into the inner cavity wall more than the surgical method using physical debridement. The method of using the vibration component with the phased array probe to peel off the biofilm is more harmless to the patient's body tissue than the current removal method. In the invention, the carrier and the nano-magnetic beads are used to carry the medicine to reach the biofilm site, so that the medicine can perform its functions more accurately. This method can reduce the dose of the drug, avoid damage to the tissue, and reduce the burden of the body's metabolic drugs. The invention can be performed directly from the outside of the patient who placed the urinary catheter, and the removed biofilm is discharged out of the body through the urinary catheter. The device can also enter the patient's bladder along the urinary catheter, and it is easier to grasp the focus position of vibration.
除此之外,振動組件用以剝離大部分顯而易見的生物膜,但無法清除空間內所有的細菌。手術之後細菌仍會快速叢生,再次形成生物膜。另一方面,各式藥劑(例如抗生素)也無法輕易穿越生物膜的保護,即使提高到最大限度劑量也無法完全清除生物膜內的細菌。本發明之系統進一步結合互補兩者的優點,用振動組件剝離下大部分的可視的生物膜,同時 使載體釋放藥劑,剝離下的大部分生物膜可以透過其他方式流出腔體而移除,剩餘留在腔體內的少量生物膜當中的細菌或游離的細菌則會被藥劑消滅。藉此,本發明清除生物膜的效果遠優於現有的生物膜清洗技術。 In addition, the vibration module is used to strip most of the obvious biofilms, but it cannot remove all bacteria in the space. Bacteria will still clump quickly after the operation and form a biofilm again. On the other hand, various drugs (such as antibiotics) cannot easily pass through the protection of the biofilm, and even if the dose is increased to the maximum, the bacteria in the biofilm cannot be completely removed. The system of the present invention further combines the advantages of the complementary two, peeling off most of the visible biofilm with the vibration component, and at the same time The carrier releases the agent, and most of the peeled biofilm can be removed by flowing out of the cavity through other methods, and the bacteria or free bacteria remaining in the small amount of biofilm remaining in the cavity will be eliminated by the agent. Therefore, the effect of removing the biofilm by the present invention is far superior to the existing biofilm cleaning technology.
1‧‧‧生物膜清除系統 1‧‧‧Biofilm removal system
2‧‧‧清除設備 2‧‧‧Clear device
3‧‧‧載體 3‧‧‧ carrier
4‧‧‧生物膜 4‧‧‧biofilm
5‧‧‧腔體 5‧‧‧ Cavity
21‧‧‧第一探頭 21‧‧‧first probe
23‧‧‧磁控組件 23‧‧‧Magnetron assembly
24‧‧‧磁力遮蔽 24‧‧‧ Magnetic shielding
25‧‧‧振動組件 25‧‧‧Vibration components
30‧‧‧熱敏脂膜 30‧‧‧ heat sensitive lipid film
32‧‧‧抑菌物質 32‧‧‧ Bacteriostatic substance
37‧‧‧生物膜配體 37‧‧‧Biofilm ligands
38‧‧‧奈米磁珠 38‧‧‧Nano Magnetic Beads
50‧‧‧內腔壁 50‧‧‧ Inner cavity wall
51‧‧‧液體 51‧‧‧Liquid
251‧‧‧振動元件 251‧‧‧Vibration element
圖1為本發明一具體實施例中腔體與其內之生物膜之示意圖。 FIG. 1 is a schematic diagram of a cavity and a biofilm in the cavity according to a specific embodiment of the present invention.
圖2為本發明一具體實施例中載體之示意圖。 FIG. 2 is a schematic diagram of a carrier in a specific embodiment of the present invention.
圖3為本發明一具體實施例中清除設備之示意圖。 FIG. 3 is a schematic diagram of a cleaning device in a specific embodiment of the present invention.
圖4為本發明一具體實施例中生物膜清除系統之示意圖。 FIG. 4 is a schematic diagram of a biofilm removal system in a specific embodiment of the present invention.
圖5為本發明另一具體實施例中清除設備之示意圖。 FIG. 5 is a schematic diagram of a cleaning device according to another embodiment of the present invention.
圖6為本發明另一具體實施例中載體之示意圖。 FIG. 6 is a schematic diagram of a carrier according to another embodiment of the present invention.
為了讓本發明的優點,精神與特徵可以更容易且明確地了解,後續將以實施例並參照所附圖式進行詳述與討論。值得注意的是,這些實施例僅為本發明代表性的實施例。但是其可以許多不同的形式來實現,並不限於本說明書所描述的實施例。相反地,提供這些實施例的目的是使本發明的公開內容更加透徹且全面。 In order to make the advantages, spirits and features of the present invention easier and clearer, it will be detailed and discussed in the following with reference to the embodiments and the accompanying drawings. It is worth noting that these examples are only representative examples of the present invention. But it can be implemented in many different forms and is not limited to the embodiments described in this specification. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
在本發明公開的各種實施例中使用的術語僅用於描述特定實施例的目的,並非在限制本發明所公開的各種實施例。如在此所使用單數形式係也包括複數形式,除非上下文清楚地另外指示。除非另有限定,否則在本說明書中使用的所有術語(包含技術術語和科學術語)具有與本發明公開的各種實施例所屬領域普通技術人員通常理解的涵義相同的涵義。 上述術語(諸如在一般使用的辭典中限定的術語)將被解釋為具有與在相同技術領域中的語境涵義相同的涵義,並且不將不被解釋為具有理想化的涵義或過於正式的涵義,除非在本發明公開的各種實施例中被清楚地限定。 The terms used in the various embodiments disclosed in the present invention are only used for describing the specific embodiments, and are not intended to limit the various embodiments disclosed in the present invention. As used herein, singular forms also include plural forms unless the context clearly indicates otherwise. Unless otherwise defined, all terms (including technical and scientific terms) used in this specification have the same meanings as commonly understood by one of ordinary skill in the art to which the various embodiments disclosed herein belong. The above terms (such as those defined in commonly used dictionaries) will be interpreted as having the same meaning as the contextual meaning in the same technical field, and will not be interpreted as having an idealized or overly formal meaning Unless clearly defined in the various embodiments disclosed herein.
在本說明書的描述中,參考術語”一實施例”、”一具體實施例”等的描述意指結合該實施例描述地具體特徵、結構、材料或者特點包含於本發明的至少一個實施例中。在本說明書中,對上述術語的示意性表述不一定指的是相同的實施例。而且,描述的具體特徵、結構、材料或者特點可以在任何一個或多個實施例中以合適的方式結合。 In the description of this specification, the description of the reference terms “an embodiment”, “a specific embodiment” and the like means that specific features, structures, materials, or characteristics described in connection with the embodiment are included in at least one embodiment of the present invention. . In this specification, the schematic expressions of the above terms do not necessarily refer to the same embodiment. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments.
請參閱圖1至圖4。圖1為本發明一具體實施例中腔體5與其內之生物膜4之示意圖。圖2為本發明一具體實施例中載體3之示意圖。圖3為本發明一具體實施例中清除設備2之示意圖。圖4為本發明一具體實施例中生物膜清除系統1之示意圖。本發明揭露一種生物膜清除系統1,係應用於去除一腔體5內之一內腔壁50上之生物膜4。腔體5內還容置有液體51。該生物膜清除系統1包含有一載體3與一清除設備2。載體3位於腔體5內且包含有一奈米磁珠38、用以針對性地抑制生物膜4之抑菌物質32、以及包覆抑菌物質32與奈米磁珠38之熱敏脂膜30。清除設備2包含有一磁控組件23與一振動組件25。磁控組件23用以引導奈米磁珠38帶動載體3接近生物膜4。振動組件25用以產生複數個振動並將振動聚焦至生物膜4或生物膜4外之一限定距離之內,以於液體51內產生微氣泡使生物膜4之至少一部份脫離內腔壁50,並且破壞熱敏脂膜30以釋放抑菌物質32。 See Figures 1 to 4. FIG. 1 is a schematic diagram of a cavity 5 and a biofilm 4 therein according to a specific embodiment of the present invention. FIG. 2 is a schematic diagram of a carrier 3 in a specific embodiment of the present invention. FIG. 3 is a schematic diagram of a cleaning device 2 in a specific embodiment of the present invention. FIG. 4 is a schematic diagram of a biofilm removal system 1 in a specific embodiment of the present invention. The present invention discloses a biofilm removal system 1 for removing a biofilm 4 from an inner cavity wall 50 in a cavity 5. A liquid 51 is also contained in the cavity 5. The biofilm removal system 1 includes a carrier 3 and a removal device 2. The carrier 3 is located in the cavity 5 and includes a nanomagnetic bead 38, a bacteriostatic substance 32 for targeted inhibition of the biofilm 4, and a thermosensitive lipid film 30 covering the bacteriostatic substance 32 and the nanomagnetic bead 38. . The cleaning device 2 includes a magnetron component 23 and a vibration component 25. The magnetic control component 23 is used to guide the nano-magnetic beads 38 to drive the carrier 3 to approach the biofilm 4. The vibration component 25 is used to generate a plurality of vibrations and focus the vibrations within a defined distance of the biofilm 4 or one of the outside of the biofilm 4 so as to generate micro-bubbles in the liquid 51 to cause at least a part of the biofilm 4 to escape from the inner cavity wall. 50, and the thermosensitive lipid film 30 is destroyed to release the bacteriostatic substance 32.
本發明中主要使用兩種原理協同清除生物膜4,一者是物理性的清除,利用空穴效應的能量使生物膜4從內腔壁50上剝離。其後可利用 腔體5的開口自然排出剝離的生物膜。另一者是生化性的清除,利用磁場帶動載體3到生物膜4處再釋放其內之抑菌物質32。此兩種清除方法各有優劣,物理性清除難以消滅不易偵測之微小生物膜中的細菌,而生化性清除難以毒殺大範圍生物膜內的細菌。然而藉由本發明可以在同一療程中進行兩種清除方法,且兩者皆可利用振動組件25產生的振動達成清除,使得清除生物膜的功效較傳統方法更有效率。 In the present invention, two principles are used to remove the biofilm 4 in cooperation. One is physical removal, and the energy of the hole effect is used to peel the biofilm 4 from the inner cavity wall 50. Available later The opening of the cavity 5 naturally discharges the peeled biofilm. The other is biochemical removal. The magnetic field is used to drive the carrier 3 to the biofilm 4 and then release the antibacterial substance 32 in the biofilm 4. These two methods of removal have their own advantages and disadvantages. It is difficult to physically remove bacteria in tiny biofilms that are difficult to detect, and biochemical removal is difficult to poison bacteria in a wide range of biofilms. However, with the present invention, two removal methods can be performed in the same course of treatment, and both can use the vibration generated by the vibration component 25 to achieve removal, so that the effect of removing biofilm is more efficient than the traditional method.
所述之腔體5可以是指膀胱、尿道、或其他含有液體、高濕度的器官,也可以是用以容置液體的醫療器材、用以輸送液體的醫療器材等,但不限於此。所述的生物膜4是指因為細菌孳生而產生的基質,使細菌於其中產生群落。所述之熱敏脂膜30為熱敏感性奈米脂質體所形成。所述的抑菌物質32係可以針對不同種類的細菌達成泛用性或專一性的抑制效果,進而抑制生物膜形成或擴增,或是直接的殺死細菌。例如針對大腸桿菌的抗生素、放射性物質、針對抗原的抗體、從載體3內釋放後會產生熱能的化合物、針對某種病毒或某種細菌的疫苗、酒精、殺菌劑或消毒劑等有殺菌抑菌效果之化合物。 The cavity 5 may refer to a bladder, a urethra, or other organs containing liquid and high humidity, and may also be a medical device for holding liquid, a medical device for transmitting liquid, and the like, but is not limited thereto. The biofilm 4 refers to a substrate produced by the breeding of bacteria, so that the bacteria produce a community therein. The heat-sensitive lipid film 30 is formed by heat-sensitive nano-liposomes. The bacteriostatic substance 32 can achieve universal or specific inhibition effects against different types of bacteria, thereby inhibiting biofilm formation or expansion, or directly killing bacteria. For example, antibiotics against Escherichia coli, radioactive substances, antibodies against antigens, compounds that generate heat energy when released from the carrier 3, vaccines against certain viruses or bacteria, alcohol, bactericides or disinfectants, etc. Effective compounds.
載體3內包含的元素當中,抑菌物質32也可以被一環境改善物質取代。原則上環境改善物質並非直接抑制細菌,但可以改變腔體內環境,使腔體免疫力增強、細菌不易生長或生物膜不易形成。環境改善物質可以是一種益菌,該益菌對生物體較無害,但是該益菌會改變所在的腔體環境,這樣的環境不適合部分菌種的生長,進而排斥對生物體有害的細菌。環境改善物質可以是一種酸性化合物或鹼性化合物,該化合物釋放時會改變腔體內的酸鹼值,使得細菌在此酸鹼值之下死亡,或是不易在此酸鹼值 之腔體內生長。當該腔體係為生物體的一個器官,環境改善物質可以是一種營養劑以使該器官獲得足夠營養,進而使器官健全,自然提升免疫力;當器官或組織因細菌感染而受損時,環境改善物質可以是一種生物修復因子,改善器官組織,使其恢復到原有的免疫能力。 Among the elements contained in the carrier 3, the bacteriostatic substance 32 may also be replaced by an environment improving substance. In principle, the environment-improving substance does not directly inhibit bacteria, but it can change the internal environment of the cavity, enhance the immunity of the cavity, make it difficult for bacteria to grow, or prevent the formation of biofilms. The environment-improving substance can be a beneficial bacteria, which is relatively harmless to the organism, but the beneficial bacteria will change the environment of the cavity in which it is located. Such an environment is not suitable for the growth of some species of bacteria, thereby repelling harmful bacteria to the organism. The environment-improving substance can be an acidic compound or a basic compound. When the compound is released, it will change the pH value of the cavity, causing bacteria to die below this pH value, or it is not easy to reach this pH value. Growth inside the cavity. When the cavity system is an organ of an organism, the environment-improving substance can be a nutrient to make the organ get sufficient nutrition, thereby making the organ healthy and naturally improving immunity; when the organ or tissue is damaged by bacterial infection, the environment The improving substance can be a biological repair factor, which can improve organs and tissues and restore their original immunity.
在本發明中,環境改善物質和該抑菌物質32可以合理的相互取代或者是同時被包含於該載體3之內。 In the present invention, the environment-improving substance and the bacteriostatic substance 32 can be reasonably replaced with each other or be contained in the carrier 3 at the same time.
所述之腔體5並非密閉的構造,或者說,在至少部分情況下並非密閉構造,以便於載體3進入腔體5內,以及便於剝離之生物膜4離開腔體5內。本發明可以應用在清除生物體的排泄系統內的生物膜,此時腔體5可能是膀胱或是尿道。載體3在腔體5外形成,且可以藉由導入、服用、注射、輸液等方式進入腔體5內。於一具體實施例中,腔體5係為膀胱,藉由已經裝設於患者身上之導尿管注射載體3進入膀胱中。清除設備2不須侵入腔體5內部,清除設備2在醫學上定義可為非侵入式治療設備,被剝離下來的生物膜4再經由導尿管排出體外。再另一實施例中,清除設備2也可以藉由現有管道進入腔體5內部,例如藉由導尿管進入膀胱內部,藉此在手術時更容易掌控振動的聚焦位置。 The cavity 5 is not a sealed structure, or in other words, it is not a sealed structure at least in part, so that the carrier 3 can enter the cavity 5 and the peeled biofilm 4 can leave the cavity 5. The present invention can be applied to clear biofilm in the excretory system of the living body. At this time, the cavity 5 may be a bladder or a urethra. The carrier 3 is formed outside the cavity 5 and can be introduced into the cavity 5 by means of introduction, taking, injection, infusion, and the like. In a specific embodiment, the cavity 5 is a bladder, which is introduced into the bladder through a urinary catheter injection carrier 3 already installed on the patient. The removal device 2 does not need to invade the interior of the cavity 5. The removal device 2 is medically defined as a non-invasive treatment device. The stripped biofilm 4 is then discharged through the catheter. In still another embodiment, the removal device 2 can also enter the interior of the cavity 5 through an existing tube, for example, the inside of the bladder through a urinary catheter, thereby making it easier to control the focus position of the vibration during surgery.
本發明之去除腔體內生物膜的方法可以針對生物體內的生物膜進行去除,或是針對醫療器材內的生物膜進行去除。利用振動組件讓生物膜剝落的機理,比起利用物理性清創的手術方式更能將深入到內腔壁上的生物膜清除乾淨。本發明利用振動組件讓生物膜剝落的方法,比起現今的清除方法更不傷害患者之身體組織。本發明利用載體與奈米磁珠乘載抑菌物質到達生物膜部位,可以使抑菌物質更精準地發揮功效。藉此方法 可降低抑菌物質劑量,進而減少身體代謝抑菌物質的負擔,也降低細菌抗藥性的程度。本發明可直接讓清除設備沿患者之導尿管進入膀胱進行清除,或是從體外直接進行清除,被去除掉的生物膜再經由導尿管排出體外。 The method for removing a biofilm in a cavity of the present invention can be used to remove a biofilm in a living body, or to remove a biofilm in a medical device. The mechanism of using the vibrating component to peel off the biofilm can remove the biofilm deep into the inner cavity wall more than the surgical method using physical debridement. The method of using the vibrating component to peel off the biofilm is less harmful to the patient's body tissue than the current removal method. In the invention, the carrier and the nano-magnetic beads are used to multiply the bacteriostatic substance to the location of the biofilm, so that the bacteriostatic substance can exert its function more accurately. By this method It can reduce the dose of bacteriostatic substances, thereby reducing the burden on the body's metabolism of bacteriostatic substances, and also reduce the degree of bacterial resistance. The invention can directly remove the removal device into the bladder along the catheter of the patient, or directly remove it from the outside of the body, and the removed biofilm is then discharged out of the body through the catheter.
振動組件25進一步包含有複數個振動元件251。振動元件251排列形成相位式陣列。每一振動元件251依序產生振動且振動之能量於同一時間抵達生物膜4或生物膜4外之限定距離之內。限定距離係為30mm。藉由此限定距離大致可以劃分出一有效操作範圍。有效操作範圍距離生物膜4的最遠距離即為所述限定距離。 The vibration assembly 25 further includes a plurality of vibration elements 251. The vibration elements 251 are aligned to form a phased array. Each vibration element 251 sequentially generates vibrations and the energy of the vibrations reaches the biofilm 4 or within a limited distance outside the biofilm 4 at the same time. The limited distance is 30mm. An effective operating range can be roughly divided by limiting the distance. The longest distance from the effective operating range to the biofilm 4 is the defined distance.
於一具體實施例中,振動組件25係為超音波振動組件,且此超音波振動組件具有相位式陣列的超音波元件。 In a specific embodiment, the vibration component 25 is an ultrasonic vibration component, and the ultrasonic vibration component has a phased array of ultrasonic elements.
就實務應用而言,振動組件25可以利用高能聚焦超聲波技術(High-intensity focused ultrasound)以達成能量於同一時間抵達所需位置。其原理為每一振動元件251與目標位置之距離與角度皆不同,但是其振動波傳遞速度相同。當距離目標位置較遠的振動元件251先產生振動,在極短的時間之內距離目標位置較近的振動元件251再產生振動,即會發生兩個振動能量同時到達目標位置,使目標位置瞬間接收高能量而產生後續的物理現象。使用此技術之好處為在振動組件25與目標位置之間的物質不會接收到瞬間高能量而有劇烈影響。此技術使用在清除生物體內生物膜時,即可避免生物膜與振動組件25之間或周遭的組織器官受到傷害。另一方面,又可以減少被組織器官吸收掉的能量,而有足夠的能量到達目標位置之生物膜。當能量聚焦在生物膜4之中時,振動能量使生物膜內產生熱能,此熱能可超過40度,破壞生物膜中細菌的生理或結構,從而使細菌死亡。或者再 另一實施例中,振動能量影響細菌的染色體,使染色體斷裂而致使細菌死亡。 For practical applications, the vibration component 25 can use high-intensity focused ultrasound technology to achieve that the energy reaches the desired position at the same time. The principle is that the distance and angle between each vibration element 251 and the target position are different, but the transmission speed of the vibration wave is the same. When the vibrating element 251 far from the target position vibrates first, and the vibrating element 251 closer to the target position vibrates again within a very short time, two vibration energy will reach the target position at the same time, making the target position instantaneous Receiving high energy causes subsequent physical phenomena. The advantage of using this technology is that the material between the vibrating component 25 and the target location will not receive a momentarily high energy and will have a severe impact. This technology is used to remove tissues and organs between or around the biofilm and the vibration component 25 when the biofilm is removed from the body. On the other hand, it can reduce the energy absorbed by tissues and organs, and have enough energy to reach the biofilm of the target location. When the energy is focused in the biofilm 4, the vibration energy causes thermal energy in the biofilm. This thermal energy can exceed 40 degrees, destroying the physiology or structure of bacteria in the biofilm, thereby causing the bacteria to die. Or again In another embodiment, the energy of the vibration affects the chromosomes of the bacteria, causing the chromosomes to break and causing the bacteria to die.
於一具體實施例中,本發明係利用振動聚焦產生接觸生物膜之微氣泡,且微氣泡消滅時產生的壓力波作用在生物膜上,以使生物膜之至少一部份脫離內腔壁。進一步來說,當內腔內的液體和生物膜的胞外物質受到振動聚焦時,微氣泡將會產生於生物膜之表面、生物膜內部和內腔壁與生物膜之間中至少一者。因此當為氣泡消滅時所產生的壓力波將會作用於生物膜表面、生物膜內部和內腔壁與生物膜之間中至少一者,進而使生物膜間或生物膜與內腔壁間產生間隙而脫離。 In a specific embodiment, the present invention uses vibration focusing to generate microbubbles that contact the biofilm, and the pressure wave generated when the microbubbles are destroyed acts on the biofilm, so that at least a part of the biofilm is separated from the inner cavity wall. Further, when the liquid in the inner cavity and the extracellular material of the biofilm are focused by vibration, microbubbles will be generated on at least one of the surface of the biofilm, the interior of the biofilm, and between the wall of the inner cavity and the biofilm. Therefore, the pressure wave generated when the bubble is destroyed will act on at least one of the surface of the biofilm, the interior of the biofilm, and the space between the inner cavity wall and the biofilm, and then the biofilm or between the biofilm and the inner cavity wall will be generated. Clearance.
於一具體實施例中,振動組件25設置於相位式陣列探頭上。依據每一個振動元件與目標物間之距離依序激發各個振動元件,以使每一個振動元件依序產生振動,且各個振動之能量於同一時間抵達生物膜上。進一步來說,相位式陣列探頭所使用的技術係為控制每個振動元件於不同時間進行振動,這些振動將以波的方式進行傳遞。以目標物垂直對應於相位式陣列探頭的位置為中心點,相位式陣列探頭之振動元件以離此中心點越遠之振動元件至越近之振動元件依序開始振動,且與中心點同距離之振動元件將會同時振動。當每個振動元件振動後所產生的波皆於相同的時間到達干涉點,則這些波將會產生建設性干涉,進而聚焦在建設性干涉後之最後一個干涉點。本發明係藉由將干涉點設置於生物膜上,而使生物膜因為振動所產生的微氣泡而脫離。上述將振動聚焦之方式,可以免於讓其他未被聚焦之組織受到傷害。當能量聚焦在生物膜4周遭之操作範圍時,振動能量使腔體內產生微氣泡,微氣泡衝擊生物膜4並且消滅。微氣泡於消滅時 產生的壓力波作用在該生物膜4上,以使生物膜4之至少一部份脫離內腔壁50。在另外一個具體實施例中,調整發出的振動能量,使得振動聚焦至腔體5內以使液體51產生漩渦或擾流,藉由漩渦或擾流使該生物膜4之至少一部份脫離該內腔壁50。 In a specific embodiment, the vibration assembly 25 is disposed on a phased array probe. Each vibration element is sequentially excited according to the distance between each vibration element and the target, so that each vibration element sequentially generates vibrations, and the energy of each vibration reaches the biofilm at the same time. Furthermore, the technology used in the phased array probe is to control each vibrating element to vibrate at different times, and these vibrations will be transmitted in the form of waves. Taking the position of the target object corresponding to the phased array probe as the center point, the vibration element of the phased array probe starts to vibrate in order from the vibrational element farther from this center point to the closer vibrational element in the same distance from the center point. The vibration elements will vibrate simultaneously. When the waves generated by each vibrating element reach the interference point at the same time, these waves will produce constructive interference, and then focus on the last interference point after constructive interference. In the present invention, the interference point is set on the biofilm, so that the biofilm is detached due to micro-bubbles generated by vibration. The above-mentioned way of focusing the vibration can avoid harming other unfocused tissues. When the energy is focused on the operating range around the biofilm, the vibration energy causes micro-bubbles to be generated in the cavity, and the micro-bubbles impact the biofilm 4 and disappear. Microbubble The generated pressure wave acts on the biofilm 4 so that at least a part of the biofilm 4 is separated from the inner cavity wall 50. In another specific embodiment, the emitted vibration energy is adjusted so that the vibration is focused into the cavity 5 to cause the liquid 51 to generate a vortex or turbulence, and at least a part of the biofilm 4 is detached from the vortex or turbulence by the vortex or turbulence.内腔 墙 50。 The inner cavity wall 50.
振動組件25產生之振動之頻率係介於0.3MHz至4.0MHz。具體而言,所產生的頻率可以落於0.3MHz、0.5MHz、0.8MHz、1.0MHz、1.2MHz、2.0MHz、3.0MHz、4.0MHz,或上述的頻率之間之數值。 The frequency of the vibration generated by the vibration component 25 is between 0.3 MHz and 4.0 MHz. Specifically, the generated frequency may fall between 0.3 MHz, 0.5 MHz, 0.8 MHz, 1.0 MHz, 1.2 MHz, 2.0 MHz, 3.0 MHz, 4.0 MHz, or a value between the above frequencies.
磁控組件23除了引導磁珠靠近生物膜4,進一步還可產生高頻交流磁場,以產生熱能抑制生物膜4以及破壞熱敏脂膜30以釋放抑菌物質32。高頻交流磁場與高頻振動皆有破壞熱敏脂膜30之效果,並且同時作用在熱敏脂膜30時有加乘效果,快速地釋放更多熱敏脂膜30內的抑菌物質32。 In addition to guiding the magnetic beads close to the biofilm 4, the magnetron component 23 can further generate a high-frequency AC magnetic field to generate thermal energy to suppress the biofilm 4 and destroy the thermosensitive lipid film 30 to release the bacteriostatic substance 32. Both the high-frequency AC magnetic field and the high-frequency vibration have the effect of destroying the heat-sensitive fat film 30, and at the same time, they have a multiplier effect when they are applied to the heat-sensitive fat film 30, and quickly release more antibacterial substances 32 in the heat-sensitive fat film 30. .
由於表面張力原理,載體3大致為圓形。載體3之直徑小於0.22μm,可以是以注射或是口服的方式進入生物體中。藉由上述提到的精準的清除方式,每次使用的藥劑總量可遠少於傳統僅使用藥劑去除生物膜的方式,而達到同樣的去除效果。而精準、低濃度的藥劑則可以避免生物體的其他組織或細胞受到傷害。 Due to the principle of surface tension, the carrier 3 is substantially circular. The diameter of the carrier 3 is less than 0.22 μm, and it can be injected into the living body by injection or oral administration. With the precise removal method mentioned above, the total amount of medicament used at each time can be far less than the traditional way of removing biofilm with only medicament, and achieve the same removal effect. Precise, low-concentration drugs can prevent damage to other tissues or cells in the organism.
請參閱圖4與圖6。圖6為本發明另一具體實施例中載體之示意圖。載體3進一步包含有一生物膜配體37。生物膜配體37之第一端接合於熱敏脂膜30外側,生物膜配體37之第二端用以接合於生物膜4。當磁控組件操作載體3靠近生物膜4時,生物膜配體37會吸附於生物膜上,當清除設備2之磁控組件23發出高頻交互磁場能量時,奈米磁珠38發生振動而產生熱量使生物膜內的細菌死亡;當清除設備2發出能量破壞載體3時,釋放出的抑 菌物質可以有效地接觸到生物膜。 Please refer to FIG. 4 and FIG. 6. FIG. 6 is a schematic diagram of a carrier according to another embodiment of the present invention. The carrier 3 further includes a biofilm ligand 37. The first end of the biofilm ligand 37 is connected to the outside of the thermosensitive lipid film 30, and the second end of the biofilm ligand 37 is used to be connected to the biofilm 4. When the magnetic control component operation carrier 3 is close to the biofilm 4, the biofilm ligand 37 will be adsorbed on the biofilm. When the high frequency interactive magnetic field energy is emitted from the magnetic control component 23 of the cleaning device 2, the nano magnetic beads 38 vibrate and Generate heat to kill bacteria in the biofilm; when the cleaning device 2 emits energy to destroy the carrier 3, Bacterial substances can effectively contact the biofilm.
請參閱圖5。圖5為本發明另一具體實施例中清除設備之示意圖。於一具體實施例中,清除設備2進一步包含有一第一探頭21,第一探頭21包含有前述的磁控組件23、振動組件25與一磁力遮蔽24。磁力遮蔽24位於磁控組件23與振動組件25之間,用以減少磁控組件23對振動組件25造成的電磁效應。此實施例中,藉由磁力遮蔽24可以維持振動組件25的穩定性。此外,磁控組件23與振動組件25集中於第一探頭21,有利於單手操作。 See Figure 5. FIG. 5 is a schematic diagram of a cleaning device according to another embodiment of the present invention. In a specific embodiment, the removal device 2 further includes a first probe 21. The first probe 21 includes the aforementioned magnetron component 23, vibration component 25 and a magnetic shield 24. The magnetic shield 24 is located between the magnetron component 23 and the vibration component 25 to reduce the electromagnetic effect of the magnetron component 23 on the vibration component 25. In this embodiment, the stability of the vibration component 25 can be maintained by the magnetic shielding 24. In addition, the magnetron assembly 23 and the vibration assembly 25 are concentrated on the first probe 21, which is advantageous for one-handed operation.
於另一具體實施例中,清除設備進一步包含有第三探頭(未繪示),第三探頭設置有磁控組件,第一探頭設置有振動組件。在部分狀況下,高頻振動與磁場必須從腔體的不同角度中傳輸能量,此時需要磁控組件與振動組件位在不同探頭,有利於進行精準醫療。 In another specific embodiment, the removal device further includes a third probe (not shown), the third probe is provided with a magnetron component, and the first probe is provided with a vibration component. In some cases, high-frequency vibration and magnetic fields must transmit energy from different angles of the cavity. At this time, the magnetron component and the vibration component need to be located at different probes, which is conducive to precision medical treatment.
生物膜清除系統1進一步包含有一第二探頭(未繪示),第二探頭有一檢測組件用以接收回聲,或可以發出振動,回聲係因振動組件25產生之振動、檢測組件產生之振動、或一第三振動源產生之振動觸及該腔體與該生物膜而產生。藉由檢測組件的檢測,可以搜尋出生物膜的精確位置,再使用第一探頭21清除生物膜。於一具體實施例中,檢測組件可位於第一探頭上。 The biofilm removal system 1 further includes a second probe (not shown), and the second probe has a detection component for receiving an echo, or can emit a vibration. The echo is the vibration generated by the vibration component 25, the vibration generated by the detection component, or A vibration generated by a third vibration source touches the cavity and the biofilm. Through the detection of the detection component, the precise position of the biofilm can be searched out, and then the biofilm is removed using the first probe 21. In a specific embodiment, the detection component may be located on the first probe.
就應用上而言,檢測組件、磁控組件、振動組件可分別設置在不同的三個探頭上,也可能任意兩者位於同一探頭,也可能三者皆位於同一探頭上,端看於個案或實務上需求。 In terms of application, the detection component, magnetron component, and vibration component can be set on three different probes, or any two can be on the same probe, or all three can be on the same probe, depending on the case or Practical needs.
於本發明之一範疇中,進一步提供一種生物膜清除系統,係應用於去除一腔體內之一內腔壁上之一生物膜,生物膜清除系統包含有一 清除設備,清除設備包含有檢測組件與振動組件。檢測組件用以產生一第一振動,使腔體產生對應第一振動之一回聲,檢測組件進一步接收回聲。振動組件進一步包含有複數個振動元件形成相位式陣列,每一振動元件依序產生第二振動且該等第二振動之能量於同一時間抵達生物膜及其一範圍內,使生物膜及其範圍內產生一熱能,藉由熱能使生物膜之溫度高於內腔壁之溫度。於一具體實施例中,腔體係為膀胱,內腔壁之溫度則為生物體溫。此方式產生的熱能使生物膜溫度高於膀胱壁溫度,而大部分的細菌在較高的溫度下會死亡,因此達到殺死生物膜內細菌之效果。 In a category of the present invention, a biofilm removal system is further provided, which is used to remove a biofilm on an inner cavity wall of a cavity. The biofilm removal system includes a The cleaning device includes a detection component and a vibration component. The detection component is used to generate a first vibration, so that the cavity generates an echo corresponding to the first vibration, and the detection component further receives the echo. The vibration component further includes a plurality of vibration elements forming a phased array, and each vibration element sequentially generates a second vibration and the energy of the second vibration reaches the biofilm and a range thereof at the same time, so that the biofilm and the range thereof A thermal energy is generated inside, and the temperature of the biofilm is higher than the temperature of the inner cavity wall by the thermal energy. In a specific embodiment, the cavity system is the bladder, and the temperature of the inner cavity wall is the biological body temperature. The thermal energy generated in this way makes the temperature of the biofilm higher than the temperature of the bladder wall, and most bacteria will die at higher temperatures, thus achieving the effect of killing bacteria in the biofilm.
於本發明之另一範疇中,進一步提供一種生物膜清除系統,應用於去除一腔體內之一內腔壁上之一生物膜,生物膜清除系統包含有一載體與一清除設備。載體位於腔體內,其包含有一奈米磁珠以及用以包覆奈米磁珠之一外膜。清除設備包含有一振動組件與一磁控組件。磁控組件用以引導載體至生物膜處或生物膜周遭。振動組件用以產生一振動以破壞外膜而釋放奈米磁珠。接著磁控組件再產生一高頻交流磁場以磁振奈米磁珠產生一熱能,熱能使生物膜之溫度上升,進而殺死生物膜內部不耐高溫之細菌。 In another aspect of the present invention, a biofilm removal system is further provided for removing a biofilm on an inner cavity wall of a cavity. The biofilm removal system includes a carrier and a removal device. The carrier is located in the cavity, and includes a nanometer magnetic bead and an outer film for covering the nanometer magnetic bead. The cleaning device includes a vibration component and a magnetron component. The magnetron component is used to guide the carrier to or around the biofilm. The vibration component is used to generate a vibration to destroy the outer membrane and release the nano-magnetic beads. Next, the magnetic control component generates a high-frequency AC magnetic field to generate thermal energy by magnetically vibrating the nano-magnetic beads. The thermal energy causes the temperature of the biofilm to rise, thereby killing bacteria that are not resistant to high temperature inside the biofilm.
本發明之生物膜清除系統提供有多種清除方法。分別進行下述的清除方法可以獲得不同之效果;但下述的方法也可以彼此以合理方式組合,來達成更多元的應用方式。 The biofilm removal system of the present invention provides various removal methods. Performing the following removal methods separately can achieve different effects; however, the following methods can also be combined with each other in a reasonable manner to achieve more versatile application methods.
一種去除腔體內生物膜的方法係應用於去除附著於目標物之內腔壁上的生物膜。此方法包含以下步驟:提供含有一第一探頭的一清除設備,第一探頭包含有振動組件和磁控組件;輸入一載體至該目標物內。 載體包含有抑菌物質與奈米磁珠;將第一探頭貼近於目標物之對應外表面;控制磁控組件使載體貼近生物膜:控制振動組件產生複數個振動,並將這些振動聚焦至生物膜上;利用這些振動聚焦產生接觸生物膜之複數個微氣泡,以使生物膜之至少一部分脫離內腔壁,並且使載體釋放抑菌物質。 A method for removing a biofilm in a cavity is applied to remove a biofilm attached to an inner cavity wall of a target. The method includes the following steps: providing a removal device including a first probe, the first probe including a vibration component and a magnetron component; and inputting a carrier into the target. The carrier contains bacteriostatic substances and nano-magnetic beads; the first probe is brought close to the corresponding outer surface of the target; the magnetic control component is controlled to bring the carrier close to the biofilm: the vibration component is controlled to generate a plurality of vibrations and the vibrations are focused to the organism On the membrane; using these vibration focusing to generate a plurality of microbubbles that contact the biofilm, so that at least a part of the biofilm is detached from the inner cavity wall, and the carrier releases the antibacterial substance.
再一種去除腔體內生物膜的方法是注入載體於目標物之腔體中;利用磁控組件奈米磁珠引導奈米磁珠帶動載體接近生物膜;控制振動組件產生複數個振動,並將這些振動聚焦至生物膜或生物膜外之一限定距離之內;利用這些振動聚焦產生接觸生物膜之複數個微氣泡,以使生物膜之至少一部分脫離內腔壁;同時振動之能量或振動產生的熱能破壞熱敏脂膜以釋放抑菌物質,由於載體靠近生物膜,抑菌物質也會順利地作用到生物膜內的細菌。 Another method for removing the biofilm in the cavity is to inject the carrier into the cavity of the target; use the nanomagnetic beads of the magnetic control component to guide the nanomagnetic beads to drive the carrier to approach the biofilm; control the vibration component to generate a plurality of vibrations, and Vibration is focused to within a defined distance of the biofilm or one outside the biofilm; use these vibrations to focus to generate a number of microbubbles that contact the biofilm, so that at least a part of the biofilm is detached from the inner cavity wall; at the same time the energy of the vibration or vibration Thermal energy destroys the heat-sensitive lipid film to release the bacteriostatic substance. Because the carrier is close to the biofilm, the bacteriostatic substance can also smoothly affect the bacteria in the biofilm.
另外一種去除腔體內生物膜的方法是注入載體於該腔體中;利用載體上的生物膜配體與生物膜產生特異性結合;控制磁控組件產生高頻交流磁場使得載體內的奈米磁珠產生磁振;磁振產生高於生物體溫的熱能使生物膜內的細菌死亡;載體的熱敏脂膜因為磁振及磁振產生的熱能而被破壞,釋放出其內的抑菌物質。 Another method to remove the biofilm in the cavity is to inject the carrier into the cavity; use the biofilm ligand on the carrier to specifically bind to the biofilm; control the magnetron component to generate a high-frequency AC magnetic field to make the nanometer magnet in the carrier Beads generate magnetic vibrations; magnetic vibrations generate thermal energy higher than the body temperature to kill bacteria in the biofilm; the thermally sensitive lipid film of the carrier is destroyed due to magnetic vibrations and the thermal energy generated by the magnetic vibrations, releasing bacteriostatic substances therein.
另外一種去除腔體內生物膜的方法包含以下步驟:將振動組件貼近於腔體之對應外表面;控制振動組件產生複數個振動,並將這些振動聚焦至生物膜上;接著,利用這些振動聚焦產生接觸生物膜之複數個微氣泡,以使生物膜之至少一部分脫離內腔壁。 Another method for removing the biofilm in the cavity includes the following steps: close the vibration component to the corresponding outer surface of the cavity; control the vibration component to generate a plurality of vibrations and focus the vibrations on the biofilm; then, use these vibrations to focus and generate The plurality of micro-bubbles are contacted with the biofilm to disengage at least a part of the biofilm from the inner cavity wall.
綜上所述,本發明之振動組件用以剝離大部分顯而易見的生物膜,但無法清除空間內所有的細菌。手術之後細菌仍可能會快速叢生, 再次形成生物膜。另一方面,抑菌物質也無法輕易穿越生物膜的保護,即使提高到最大限度劑量也無法完全清除生物膜內的細菌。本發明之系統進一步結合互補兩者的優點,用振動組件剝離下大部分的可視的生物膜,同時使載體釋放抑菌物質,剝離下的大部分生物膜可以透過其他方式流出腔體而移除,剩餘留在腔體內的少量生物膜當中的細菌或游離的細菌則會被抑菌物質消滅。除了可以用抑菌物質殺死現存的細菌,也可以在載體中承載有環境改善物質,使細菌不易在腔體內孳生。藉此,本發明的效果遠優於現有的生物膜清洗技術。相較於習知技術,本發明之去除腔體內生物膜的方法,比以往利用物理性清創的手術方式更能將深入到內腔壁上的生物膜清除乾淨;本發明之方法比起現今的清除方法更不傷害患者之身體組織。 In summary, the vibration component of the present invention is used to peel off most obvious biofilms, but it cannot remove all bacteria in the space. Bacteria can still cluster quickly after surgery, A biofilm is formed again. On the other hand, bacteriostatic substances cannot easily pass through the protection of the biofilm, and even if the dose is increased to the maximum, the bacteria in the biofilm cannot be completely removed. The system of the present invention further combines the advantages of the complementary two, peeling off most of the visible biofilm with the vibration component, and at the same time causing the carrier to release the bacteriostatic substance. Most of the peeled biofilm can be removed from the cavity by other means and removed , The remaining bacteria or free bacteria in the small amount of biofilm remaining in the cavity will be eliminated by the bacteriostatic substance. In addition to killing existing bacteria with bacteriostatic substances, it is also possible to carry environmental improvement substances in the carrier, making it difficult for bacteria to breed in the cavity. Therefore, the effect of the present invention is far superior to the existing biofilm cleaning technology. Compared with the conventional technology, the method for removing the biofilm in the cavity of the present invention can remove the biofilm deeper into the wall of the inner cavity than the previous surgical methods using physical debridement; the method of the present invention is more than today The removal method does not harm the patient's body tissue.
藉由以上具體實施例之詳述,係希望能更加清楚描述本發明之特徵與精神,而並非以上述所揭露的具體實施例來對本發明之範疇加以限制。相反地,其目的是希望能涵蓋各種改變及具相等性的安排於本發明所欲申請之專利範圍的範疇內。 With the detailed description of the above specific embodiments, it is hoped that the features and spirit of the present invention can be described more clearly, rather than limiting the scope of the present invention with the specific embodiments disclosed above. On the contrary, the intention is to cover various changes and equivalent arrangements within the scope of the patents to be applied for in the present invention.
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WO2016049472A1 (en) * | 2014-09-25 | 2016-03-31 | Indiana University Research And Technology Corp. | Device and method for vibration of an implantable device |
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EP1511414B1 (en) * | 2002-05-29 | 2012-08-08 | NanoVibronix Inc. | Apparatus for treating biofilms associated with catheters |
CN101616707A (en) * | 2006-03-29 | 2009-12-30 | 纳微振动技术公司 | Be used for preventing that catheter from forming the acoustic add-on device of biofilm |
CN202808772U (en) * | 2012-07-12 | 2013-03-20 | 重庆医科大学附属儿童医院 | Ultrasound microbubble intervened bacterial biofilm experimental apparatus |
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