201138874 六、發明說明： 【發明所屬之技術領域】 本發明係關於一種藥物載體之電紡製造方法，特 一種可以控制藥物載體大小及形狀之電紡製造方法]疋 【先前技術】 在生技製藥產業，有鑑於新興蛋白質藥劑的特殊性質 及作用方式，無法以傳統給藥途徑投予個體，故藥物傳衿 系統之研發及應用漸党相關產業的重視。藥物傳輸系統的 主要目的係控制目標_可以正確作用於目標患部，、以接 升該目標藥劑的生物利用率並降低副作用。習用藥物傳 載體依照技術平台的需求性係可區分為雜性傳輸載體: 貼附性傳輸載體及控制緩釋性傳輸載體三類，其中： 1、 移植性傳輸倾：主要翻於取代或修補人 傷組織，制用-些天然或人工合成的高分子材料如 蛋白Mlagen)、幾了㈣（chit〇san)及聚甘醇酸 ⑽倉福e add)等，該高分子材質具有生物相容性及生 ，可分解性，可植人人仙提供細胞射所需之空間；如 L華ί國公告第1283585「幾丁聚醋微粒之製法及其用途」 專利案’係揭不-種利用顆粒型態幾丁聚醣 射水泥混合之複合材料，作献料細胞再生之骨㈣ 料，以改善傳統骨粉的g|定效果及副作^ 2、 貼附性傳輸載體：主要係利用—般人工合成的聚 :烯、聚氣乙烯或聚甲基丙烯酸樹脂 貼附於細胞之載體，主要針對蛋白質藥物的制，藉由貼 201138874 - 附目標部位促進細胞增生及分化的能力。 3、控制緩釋性傳輸載體：多採用一褐藻膠成分，該 褐藻膠成分係為一無毒的天然聚醣類高分子，屬一不分枝 鏈多醣體，可於二價陽離子溶液存在下形成膠狀體，可應 用於各種生物性物質或藥劑化合物的包覆，送入生物個體 内反應。.如中華民國公告第524699係揭示一種製備膠原蛋 白與生^陶究粉末複合材料微粒的方法，係混合一膠原蛋 φ 白’合液、一生醫陶瓷粉末及一褐藻膠溶液以液滴形式滴入 一二價陽離子溶液固化成數微粒型生醫材料。 而習用藥物輸送載體之製造方法大略可分為滴漏 法、乳化法及電紡等技術。滴漏法係將一目標藥劑與一高 刀子材質（如褐藻膠)之混合溶液，利用滴管操作，將該混 合溶液滴入一固化劑中（如二價陽離子溶液）進行固化反 應，以獲得數個晶球狀藥物載體，操作滴漏法製之藥 物載體的粒鼓小約為1>2毫米左右。 ^ _ ^而乳化法係將所欲包覆的目標藥劑混合一高分子材 質(如褐藻膠等）、-乳化劑及一醋類，利用一氣體推動促 ㈣過—疏水性孔洞薄膜，以形成數個乳化液滴，再加入 IS化劑使魏化液賴含之高分子材質可以膠化而形成 數個微球體，經脫水乾燥後即可得數個 ，藥物微球載體;如中華民國公告第 4求之預固化方法及裝置」專利案，即揭示—種用於乳化 、、製備藥物载體之固化方式’係將—乳化溶液與固化溶液 皮=一 γ形分叉流道，使該乳化溶液與固化溶液可以先行 ~縮短固化反應所需的時間，同時藉由該乳化溶液與 201138874 固化溶液於該γ形分叉流道中流速的控制，以獲得尺 小的藥物載體。 、乂 …然而，上述滴漏法及乳化法技術因產生藥物載體的方 式係為隨機產生，藥物載體的粒徑尺寸及數量不易控制， 所形成的藥物載體多有粒徑分布不均的問題，影變 載體的作毅果’導致目標藥劑的仙效果無法明確預 估，再者’於製造過程中，各成分之比例及各步驟之操作 皆須精確控制以維持藥物載體之製程，故所需操作時間較 長易受人為因素影響而影響藥物載體之製程，因此广 於製藥產業的應用及量產上有諸多困難。 電紡技術係近年來新興的奈米科技，具有快速且直接 的將一高分子材質轉變為奈米纖維之技術特徵，由 :二件之生物材料，多形成無定向錐狀之藥物纖維，適用 =科手術移植或是直接貼覆於外傷表面，多應用於醫學 材枓之領域，如中華民國公開第施74()472「―種 ，創傷敷料」係揭示—種將膠原蛋白、幾丁聚聽、^氧 酸性溶液以等_混合後，進行電紡製程之奈米 =薄膜’可以做為創傷敷料，具有較佳之生物性及較多 的表面積，有助於傷口癒合。 然而上述利用電纺技術所操作之生物材料，由於無定 =體外型的限制’僅能應用於移植技術或傷口敷料:而 戶;;ίΓ服、吸劑或注射等方式提供給需要患者，因此， 斤適用的藥物範圍較狹窄。 公告物材料製作之另—應用如中華民國 號-種在水相環境中利用電場製作微粒 201138874 白置人正負極之電^ 將-存於水相環境的膠原蛋 微粒膠原蛋白電場原理製作奈米尺寸之 生物體的吸收’·上述方法所=之餘較«方便且利於 釋放不具有藥物包覆； 以電纺技财缝電場轉帶電驗 則係 劑:合一幾丁聚醣溶液從一來源處至：目,： 子的鹽溶液)，使該幾丁 二= 質可以與該固化劑中金屬離子作 刀子材 高分子凝膠，包覆目標藥劑而成:::用而轉化成 製作係於單—步驟完成。 纟且細粒型藥物載體之 述之2，以電紡法製作触型之藥物紐仍存在如下所 帶有正料料，魏下才 幾丁聚聰再剌電躲操作，心，劑洛解該 具有負面料，會㈣定成分 效·哀从 节w成刀的變質而降低藥 以維持复处該幾丁聚醋與該交聯劑間的機械作用強度不足 準確估計所議_於生物體；:’= 201138874 之，電紡法雖然為所有習用藥物載體製造技術中製程最簡 作效果較佳的方式，但是，仍然存在有製程條件上 的限制瓶頸’無法得到符合需求的藥物載體應用於製藥產 業，有再改進的空間。 【發明内容】 本發明係解決習用電紡法製造藥物载體技術之問 題’提供-種藥物載體之電紡製造方法，其主要目的係得 到一高均一性粒徑之藥物載體。 、本發明次一目的係提供一種藥物載體之電紡製造方 法，以得到一形狀均勻之藥物載體。 本發明之再一目的，係為符合各種目標藥劑之藥物特 種藥物載體之電紡製造方法，可以適用於多種生 醫材料或藥物化合物之載體運輸應用。 、本發明之又一目的，係為符合各種目標藥劑之施用方 式提供-麵物載體之電紡製造方法製成多種不同形狀及 大小之藥物載體，以配合目標藥劑之施用方針。 為達到前述發明目的，本發明所運用之技術手段包含 有： 一種藥物載體之電訪製造方法，其包含：一預備步 驟，係將一目標藥劑與一褐藻混合，再由一生 理溶液配製成一混合液；一供電步驟，裝設一收集盤及一 發射器，分別容置二價陽離子固化液及該混合液，施電麼 於該收集盤及S亥發射器，使該收集盤與發射器間形成一電 場；及-電纺步驟，利用該電場牽動該混合液由該發射器 201138874 • 滴下，形成數液滴落入該收集盤，使該二價陽離子固化液 與该液滴之褐藻膠行交聯作用而產生膠體微粒，包覆該目 標藥劑而形成一藥物載體。 【實施方式】 為讓本發明之上述及其他目的、特徵及優點能更明顯 易懂，下文特舉本發明之較佳實施例，並配合所附圖j 作詳細說明如下： 工’ • 〇本發明一種藥物載體之電紡製造方法係利用電紡法 操作’使褐藻膠與二價陽離子行交聯作用產生膠體微粒而 包覆目標藥劑之操作可以較為精簡，並且準確控制所 藥物載體之粒徑大小、均勻度及外型規則。請參照第/圖 所不，係本發明—種藥物载體之電紡製造方法之步驟流 程，包含:-預備步驟S1、一供電步驟S2及一電纺步稱幻。 預備步驟si係將一目標藥劑與一褐藻膠混合，再由 —生理溶液配製成-混合液，該混合液將於後續步驟利用 • 電纺技術製成藥物載體。本實施例所採用之褐藻膠 係-天朗聚糖高分子，以2:1的比例與該目標 ^⑨合使總重I達G.G5〜G.3公克，再溶於1〇毫升去離子 .^配製成—重量百分比濃度為0.5〜3%之混合液；該褐藻膠 ^去離子水後帶有負電’可與二價陽離子反應而形成膠 的放粒’應用於細胞及藥物的包覆，該雜微粒可使該細 歧藥物的移動緩慢，達到延緩藥劑及細胞釋放的效果。 °月參照第2圖所7，供電步驟S2係準備-收集盤1 及發射器2，分別容置二價陽離子固化液及該混合液， 201138874 ^電壓於該收集盤1及發射器2，使形成—電場。立中， ^收集盤1與發射H 2之較絲設方式魅垂直架設，使 錯射器2係於該收集盤i上方怪保持 發射器2中的混合液可以由開孔21滴入該 該收集盤i之金屬板U具有導電性，可以由—導線3連接 =一電源供應H 3之-極，而該發射器2 _由該導線3 連接該電源供應H 3的另—極，以形成該電場。 本實施财，係先將該混合液注於一注入件23，再由 該幫浦24施壓推動該注人件23，使該注人件23所容置的 混合液可以透過-軟管22流通至該發射器2，以藉由控制 該幫浦24之壓力大小，調_混合液由該發射器2之開孔 21流出的速度’較佳係以每小時G 5〜3毫升的流動速度流 出。此時，該發射器2之開孔21與該收集盤i間之距離約 為10公分；開啟該電源供應器3，使該電源供應器3之兩 極之電位設定為1〜15千伏(正極)及〇千伏（負極），使該收 集盤1及發射器2間形成-電場，其電場強度係為每^位 距離(公尺)約有10〜150千伏(kv/m)之電位。 電紡步驟S3係利用該電場牽動該混合液由該發射器2 之開孔21陸續滴出（如第2圖示），此時由於表面張力之作 用，該混合液會凝聚成數液滴，而施加於該發射器2之言 電壓將該褐藻膠所帶有之電荷從該混合液内部拉至表面^ 使該表面逐漸累積相互排斥之電荷，當表面累積之電荷所 產生電壓強度超過一定值，該電壓強度可克服表面張力限 制該液滴之體積，使得該液滴之體積維持於微奈米尺度之 大小。所滴下之液滴將受該收集盤1之低電位吸引，二離 201138874 該開孔21並藉由重力加速度的輔助作用，落入該收集盤Γ 盛裂之二價陽離子固化液中’此時’該液滴中的褐藻膠可 與°亥一價陽離子交聯而成膠體微粒，並且對該目標藥劑進 行包覆而成為一藥物載體。 本實施例中，係可以針對該電場作用牽引該混合液由 該發射器2滴下之電紡技術，調整該電場強度，以控制該 藥物载體粒徑的大小及均勻度。請參照第3圖所示，其係 本發明電場與藥物載體粒徑之關係圖，其中，於電場強度 15〜30千伏/單位距離(公尺），流動速度為每小時丨毫升， 滴入二價陽離子固化液（氣化鈣溶液）中所形成的藥物载 體，其平均粒徑較大，約為1100〜1500微米（以m);而於 同樣條件但電場強度為3G〜150千伏/單位距離(公尺)之條 件下所形成的藥物載體，其平均粒徑則相對較小，最小可 達到120〜200微米（# m)之粒徑尺寸。201138874 VI. Description of the Invention: [Technical Field] The present invention relates to an electrospinning manufacturing method for a pharmaceutical carrier, and an electrospinning manufacturing method capable of controlling the size and shape of a pharmaceutical carrier. [Prior Art] In Biotechnology Pharmaceuticals In the industry, in view of the special nature and mode of action of emerging protein agents, it is impossible to invest in individuals by traditional drug delivery methods. Therefore, the research and application of drug delivery systems and the application of the relevant industries have become more important. The primary purpose of the drug delivery system is to control the target _ to act correctly on the target affected area to increase the bioavailability of the target agent and reduce side effects. The conventional drug delivery carrier can be classified into a hybrid transmission carrier according to the demand of the technology platform: an adhesive delivery carrier and a controlled release carrier, among which: 1. Transplantation transfer: mainly to replace or repair people Injury tissue, using some natural or synthetic polymer materials such as protein Mlagen, chit〇san and polyglycolic acid (10) Cangfu e add), the polymer material is biocompatible And raw, decomposable, can plant the space required for cell shooting; such as L Hua ίguo Announcement No. 1283585 "Manufacturing method and application of chitin granules" Patent case The type of chitosan shot cement mixed composite material, for the bone regeneration of the feed cell (four) material, to improve the traditional effect of the bone powder g | fixed effect and secondary work ^ 2, attached transmission carrier: mainly using artificial The synthetic poly(ene), polystyrene or polymethacrylic resin is attached to the carrier of the cell, and is mainly for the production of protein drugs, and the ability to promote cell proliferation and differentiation by attaching the target site to 201138874. 3. Controlling the sustained-release transport carrier: a brown algae component is used, and the alginate component is a non-toxic natural polysaccharide polymer, which belongs to a non-branched chain polysaccharide and can be formed in the presence of a divalent cation solution. The gel can be applied to the coating of various biological substances or pharmaceutical compounds and sent to the biological individual for reaction. For example, the Republic of China Announcement No. 524699 discloses a method for preparing collagen and raw ceramic powder composite particles by mixing a collagen egg φ white 'liquid mixture, a raw ceramic powder and a brown algae solution in droplet form. The divalent cation solution is solidified into a plurality of microscopic biomedical materials. The manufacturing method of the conventional drug delivery carrier can be roughly classified into a drip method, an emulsification method, and an electrospinning technique. The drip method is a mixed solution of a target agent and a high knife material (such as alginate), which is operated by a dropper, and the mixed solution is dropped into a curing agent (such as a divalent cation solution) to carry out a curing reaction to obtain a number. The crystal spherical drug carrier, the drug carrier of the drip-leak method has a particle size of about 1 mm and about 2 mm. ^ _ ^ The emulsification method is to mix the target agent to be coated with a polymer material (such as alginate, etc.), an emulsifier and a vinegar, and use a gas to promote the (four) over-hydrophobic pore film to form Several emulsified droplets, and then adding IS agent to make the polymer material of Weihua liquid can be gelled to form several microspheres. After dehydration and drying, several drugs and microsphere carriers can be obtained; such as the Republic of China Announcement The fourth patent pre-curing method and apparatus patent discloses that the curing method for emulsification and preparation of a drug carrier is a emulsified solution and a cured solution skin = a gamma-shaped bifurcated flow channel. The emulsified solution and the solidified solution can be used first to shorten the time required for the curing reaction, and at the same time, the flow rate of the emulsified solution and the 201138874 solidified solution in the γ-shaped bifurcated flow channel is controlled to obtain a small-sized drug carrier.乂 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而 然而The effect of changing the carrier's result is that the effect of the target drug cannot be clearly predicted. In addition, during the manufacturing process, the ratio of each component and the operation of each step must be precisely controlled to maintain the process of the drug carrier, so the required operation Longer time is susceptible to human factors and affects the process of drug carriers, so it is difficult to apply in the pharmaceutical industry and mass production. The electrospinning technology department is a new technology in recent years. It has the technical characteristics of quickly and directly converting a polymer material into nano fiber. It consists of two kinds of biological materials, which form a non-oriented cone-shaped drug fiber. = Surgical transplantation or direct attachment to the surface of the wound, used in the field of medical materials, such as the Republic of China Public Report 74 () 472 "- kinds, wound dressings" revealed that the species will be collagen, chitin After listening, the oxy-acid solution is mixed, the nano-film of the electrospinning process can be used as a wound dressing, which has better biological properties and more surface area, and contributes to wound healing. However, the above-mentioned biomaterials operated by electrospinning technology can only be applied to transplant technology or wound dressings because of the indefinite = in vitro type of restriction: and the patient is required to provide the patient, so The range of drugs that can be used is relatively narrow. Another material for the production of bulletin materials - such as the Republic of China - the use of electric fields in the water environment to make particles 201138874 white set people positive and negative electric ^ will be - in the aqueous environment of collagen egg microparticle collagen electric field principle to make nano The absorption of the size of the organism '· The above method = more than convenient and conducive to release without drug coating; to electrospinning chemical electric field electric field transfer test agent: a single chitosan solution from a source To: the purpose, the salt solution of the sub-component, so that the metal can be used as a polymer gel of the metal ion in the curing agent, and the target agent is coated::: used to convert into a production department In the single-step completion.纟 and the fine-grained drug carrier 2, the electro-spinning method to make the touch-type drug New Zealand still exists as follows with the positive material, Wei Xia Cai Ding Ju Cong and then 剌 剌 躲 , , 心 心 心 心 心 心 心Material, will (4) set the effect of the effect of the sorrow from the knot of the knife to reduce the quality of the knife to maintain the recovery of the mechanical strength of the chitosan and the cross-linking agent is not accurate estimation of the estimated _ in the organism;: ' = 201138874, although the electrospinning method is the best way to make the process of the conventional drug carrier manufacturing technology the best, but there are still bottlenecks in the process conditions, and the drug carrier that meets the demand cannot be obtained for the pharmaceutical industry. The space for improvement. SUMMARY OF THE INVENTION The present invention is to solve the problem of the conventional electrospinning method for producing a pharmaceutical carrier technology. The electrospinning method for providing a pharmaceutical carrier is mainly aimed at obtaining a drug carrier having a high uniform particle size. A second object of the present invention is to provide a method of electrospinning a pharmaceutical carrier to obtain a uniform shaped pharmaceutical carrier. Still another object of the present invention is an electrospinning manufacturing method for a drug-specific pharmaceutical carrier conforming to various target agents, which can be applied to carrier transportation applications of various biomedical materials or pharmaceutical compounds. A further object of the present invention is to provide a pharmaceutical carrier of a plurality of different shapes and sizes for the electrospinning method of providing a surface carrier in accordance with the application of various target agents to match the application policy of the target agent. In order to achieve the foregoing object, the technical means used in the present invention comprises: a method for manufacturing a drug carrier, comprising: a preliminary step of mixing a target agent with a brown alga and then preparing a physiological solution. a liquid mixture step; a power supply step, a collection tray and a transmitter are respectively arranged to accommodate the divalent cation solidifying liquid and the mixed liquid, and the electricity is applied to the collecting tray and the S-hai emitter to make the collecting tray and the emitting An electric field is formed between the devices; and an electrospinning step is utilized to draw the mixed solution from the emitter 201138874 to drip, forming a plurality of droplets falling into the collection tray, and causing the divalent cation solidifying liquid and the droplets of brown algae The colloidal cross-linking action produces colloidal particles that coat the target agent to form a drug carrier. BRIEF DESCRIPTION OF THE DRAWINGS The above and other objects, features, and advantages of the present invention will become more <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; The electrospinning method for inventing a pharmaceutical carrier utilizes an electrospinning operation to "crosslink the alginate and the divalent cation to produce colloidal particles, and the operation of coating the target agent can be relatively simple, and accurately control the particle size of the drug carrier. , uniformity and appearance rules. Please refer to the figure/FIG., which is a flow chart of the electrospinning manufacturing method of the present invention, comprising: a preliminary step S1, a power supply step S2 and an electrospinning step. The preliminary step si is to mix a target agent with a brown algae gel, and then to prepare a mixture liquid from a physiological solution, which will be used in a subsequent step to make a drug carrier by electrospinning. The alginate-dragon polysaccharide polymer used in the present embodiment is combined with the target ^9 in a ratio of 2:1 to make the total weight I reach G.G5~G.3 g, and then dissolved in 1 ml. The ion is prepared into a mixture of 0.5% to 3% by weight; the alginate is deionized water and has a negative electric charge, which can be reacted with divalent cations to form a gel, which is applied to cells and drugs. The coating, the microparticles can slow the movement of the fine drug, and achieve the effect of delaying the release of the drug and the cells. Referring to FIG. 2, the power supply step S2 is to prepare a collecting tray 1 and a transmitter 2, respectively accommodating the divalent cation solidifying liquid and the mixed liquid, and the voltage is applied to the collecting tray 1 and the emitter 2, Form - electric field. In the center, the collection tray 1 and the emission H 2 are vertically erected so that the erroneous device 2 is attached to the collection tray i and the mixture in the emitter 2 can be dropped into the opening 21. The metal plate U of the collecting plate i is electrically conductive and can be connected by the wire 3 = a power supply H 3 - and the emitter 2 is connected by the wire 3 to the other electrode of the power supply H 3 to form The electric field. In the implementation, the mixed liquid is injected into an injection member 23, and the injection member 23 is pressed and pushed by the pump 24, so that the mixed liquid contained in the injection member 23 can be circulated through the hose 22 to The emitter 2, by controlling the pressure of the pump 24, adjusts the speed at which the mixture flows out of the opening 21 of the emitter 2, preferably at a flow rate of G 5 to 3 ml per hour. At this time, the distance between the opening 21 of the emitter 2 and the collecting tray i is about 10 cm; the power supply 3 is turned on, so that the potential of the two poles of the power supply 3 is set to 1 to 15 kV (positive And 〇 kV (negative electrode), an electric field is formed between the collecting tray 1 and the emitter 2, and the electric field strength thereof is a potential of about 10 to 150 kV (kv/m) per unit distance (meter). . The electrospinning step S3 uses the electric field to pull the mixed liquid from the opening 21 of the emitter 2 (as shown in FIG. 2), and the mixture will condense into a plurality of droplets due to the surface tension. The voltage applied to the emitter 2 pulls the charge carried by the alginate from the inside of the mixture to the surface, causing the surface to gradually accumulate mutually repulsive charges, and when the electric charge accumulated on the surface generates a voltage exceeding a certain value, The voltage intensity overcomes the surface tension to limit the volume of the droplet such that the volume of the droplet is maintained at a micronitometer scale. The dropped droplets will be attracted by the low potential of the collecting tray 1, and the opening 21 of 201138874 will be dropped into the divalent cation solidifying liquid of the collecting tray ' by the auxiliary action of gravity acceleration. The alginate in the droplet can be crosslinked with the monovalent cation to form colloidal particles, and the target agent is coated to form a drug carrier. In this embodiment, the electrospinning technique of pulling the mixed liquid from the emitter 2 can be applied to the electric field to adjust the electric field strength to control the size and uniformity of the particle size of the drug carrier. Please refer to FIG. 3, which is a relationship diagram between the electric field of the present invention and the particle size of the drug carrier, wherein the electric field intensity is 15 to 30 kV/unit distance (meter), and the flow velocity is 丨ml per hour. The drug carrier formed in the divalent cation solidifying liquid (calcium carbonate solution) has a larger average particle diameter of about 1100 to 1500 μm (in m); and under the same conditions, the electric field strength is 3 G to 150 kV. The drug carrier formed under the condition of a unit distance (meter) has a relatively small average particle size and a minimum particle size of 120 to 200 micrometers (#m).
隨時依需求調整改變電場強度， ，以配合目標藥劑之使用製 使该藥物载體之應用可更廣 備各種粒徑尺寸的藥物載體， 泛。 另外，本發明之褐藻膠與二 二價陽離子間的交聯作用會 201138874 因，價陽離子的不同而使該交聯關係略有差異，可相對影 β «亥褐藻膠產生勝體微粒的程度及對目標藥劑的包覆情 形；因此’由二價陽離子固化液的選擇可使所製成藥物^ 體呈現不同型式’以配合該目標藥劑的施用情形。請參照 第5a〜5h圖所係分別選用不同之二價陽離子固化液， 包含5〜25%之硫酸銅溶液、氣化辦溶液、氣化铜溶液或氣 化鐵冷液’为別與本發明混合液中的褐藻膠行交聯而 不同型態之藥物载體。其中，由第5a、5b、5c及5d圖， 依序係舰合液之液滴於_ 25%硫_溶液、氯化妈溶 液、氣化鋇溶液及氣化鐵溶液中所形成的藥物載體，皆係 呈現大小均勻且外型規則的微球體，而不同二價陽離子固 化液作用下’所形成微球體之外型略有差異，如第5d圖， 於氣化鐵溶液巾所形成的藥物健係略呈擴圓狀之微球 體。 承上所述，請再參照第5e、5f、5g及5h圖，由四種 二價陽離子固化液所形成的藥物載體經乾燥處理後，以一 掃描式電子顯微鏡(SEM)觀察則可明顯分辨該藥物載體之 形狀差異；其中，第元圖，於硫酸銅溶液中所形成的藥物 載體，於乾燥後係呈現圓環狀；第分圖，於氣化鈣溶液中 形成的藥物載體，於乾燥後係呈現葡萄球狀；由第5g圖， 於氣化鋇溶液中所形成的藥物載體，於乾燥後係呈現單球 狀；而由第5h圖，於氯化鐵溶液中所形成的藥物载體，於 乾燥後係呈現圓板狀。 由上述各操作步驟’本發明之褐滿膠，溶解於一般生 理溶液的情況下即帶有負電，可於電紡操作中受電場牽 一 12 — 201138874 引，故不需要再以-酸性溶液或驗性溶液輔助其帶電性， 而般生理洛液不會影響目標藥劑本身的性質而降低其藥 =因此’本發明之褐藻膠可與多種藥劍配合使用而免於 ^受溶劑之干擾使藥缝f之虞；本發社褐轉與二價 陽離子之父聯關係較緊密，而所產生膠體化之褐藻膠具有 足夠的機械強度以維持所形成藥物載體的結構，因此，該 樂^體之形狀及外觀較為整轉則，並且藉由電纺操作 之電場辅助而有效控制該藥物载體粒徑的大小及均勻度， 大ί均一、粒徑均勾且外型規則之藥物載體，故可 1古確估异該目標藥劑於生物體内釋放的速率與情形，並 有效評倾目標_騎生物_侧效果。 華物由二價陽離子固化液的選擇可獲得形狀差異的 ==二照藥物應力的原理，不同形狀的藥物載體， 因而釋放及仙的情形也同樣有所差異， 之效果及作用情形，而應用此原理， =欠？之藥物載體，可配合目標藥劑本身的作 本；月藥針，而達到不同程度的緩釋作用效果，使 體t藥物傳輸應用可以更符合生物個體情二 兩&揮目払藥劑的施藥效果。 二價紡製造方法，係由褐藻膠與 件，製成平灼用匕覆目標樂劑’配合電紡操作條 &成和味啤勻的藥物健， 體於生物體内釋放目桿筚1异該樂物载 整該藥物載體的粒μ 依照使用需要調 及作用效果之功效小’具有提升該藥物载體緩釋效果 —13 一 201138874 二俨藥物載體之電紡製造方法’係由褐藻膠與 :貝m =交聯作用包覆目標藥劑，配合電紡操作條 於味物勾、規則之藥物載體’可提升該藥物载體 ；&緩釋及作用的穩定性，為本發明之功效。 本發明一種藥物載體之電紡製造方法，係由褐藻膠之 膠體微粒包覆目標藥劑，該褐藻膠係溶於—生理溶劑不會 對目標藥劑本身造成負面影響，適用於各種生醫材料或藥 物化合物之包覆，具有安全使用之功效。 、 本發明-種藥物載體之電紡製造方法，係由二價陽離 載條件’而製成形狀差異之藥物 f n各種樂劑之施用特性發揮緩釋效果，以配合 該藥劑之㈣方針’具有擴大藥物制應用層面之功效。 雖然本發邮湘上述較佳實補揭示，然其並非 ^艮定本發明，任何熟習此技藝者在不脫離本發明之精神 t圍之内，相對上述實施例進行各種更動與修改仍屬本 發m技術範疇，因此本發明之保護範圍當視後附 之申清專利範圍所界定者為準。 —14 — 201138874 【圖式簡單說明】 第1圖：本發明一種藥物載體之電纺製造方法之步驟流 程。 、 第2圖.本發明—種藥物載體之電纺製造方法之供電步 驟示意圖。 第3圖本么明一種藥物载體之電纺製造方法之電場強 度與載體粒徑關係圖。 第4 a圖The electric field strength can be adjusted according to the needs at any time, so as to match the use of the target medicament, the application of the drug carrier can be more widely used for drug carriers of various particle sizes. In addition, the cross-linking effect between the alginate and the di-divalent cation of the present invention will be slightly different due to the difference in valence cations, and the cross-linking relationship may be slightly different. The coating of the target agent; therefore, 'the selection of the divalent cation solidifying liquid allows the resulting drug body to assume a different type' to match the application of the target agent. Please refer to paragraphs 5a to 5h for different divalent cation solidification liquids, including 5~25% copper sulfate solution, gasification solution, vaporized copper solution or gasified iron cold liquid. The alginate in the mixed solution is cross-linked and different types of drug carriers. Among them, from the 5th, 5b, 5c and 5d diagrams, the drug carrier formed by the droplets of the ship's liquid mixture in _ 25% sulfur_solution, chlorinated mother solution, gasification hydrazine solution and gasified iron solution All of them are microspheres with uniform size and regular shape, and the microspheres formed under the action of different divalent cation solidification liquids are slightly different. For example, in Figure 5d, the drugs formed in the gasified iron solution towel The health system is slightly rounded microspheres. According to the above, please refer to the 5e, 5f, 5g and 5h diagrams. The drug carrier formed by the four divalent cation solidifying liquids can be clearly distinguished by a scanning electron microscope (SEM) after drying. a difference in shape of the drug carrier; wherein, the digraph, the drug carrier formed in the copper sulfate solution is in the form of a ring after drying; the first figure, the drug carrier formed in the vaporized calcium solution, is dried The posterior line is in the form of a grape globule; from the 5th figure, the drug carrier formed in the gasification hydrazine solution is monosphere after drying; and the drug formed in the ferric chloride solution is shown in Figure 5h. The body is rounded after drying. According to the above various operation steps, the brown plastic of the present invention is negatively charged in the case of being dissolved in a general physiological solution, and can be induced by an electric field in an electrospinning operation, so that it is not necessary to use an acidic solution or The test solution assists its chargeability, and the normal physiological solution does not affect the properties of the target drug itself and lowers its drug. Therefore, the alginate of the present invention can be used in combination with a variety of medicine swords to avoid interference with solvents. The gap between the hair and the divalent cation is tighter, and the colloidal alginate has sufficient mechanical strength to maintain the structure of the formed drug carrier, therefore, the music body The shape and appearance are relatively complete, and the size and uniformity of the particle size of the drug carrier are effectively controlled by the electric field assist of the electrospinning operation, and the drug carrier is uniform in size and has a uniform particle size and a regular shape. 1 Gu guessed the rate and situation of the release of the target agent in the body, and effectively evaluated the target _ riding creature _ side effect. The choice of divalent cation solidifying liquid can obtain the difference of the shape of the == two-medicine stress principle, the drug carrier of different shapes, so the release and the situation of the fairy are also different, the effect and the action situation, and the application This principle, = owed? The drug carrier can be combined with the target drug itself; the monthly drug needle can achieve different degrees of sustained release effect, so that the body t drug delivery application can be more in line with the biological individual intelligence and the application of the drug effect. The bivalent spinning manufacturing method is made up of alginate and pieces, and is made into a flat burning sputum covering target music agent' with electrospinning operation strip & The granule μ of the drug carrier is loaded with the granule μ of the drug carrier according to the need of use, and has the effect of enhancing the sustained release effect of the drug carrier. 13-1313838874 The electrospinning method for preparing the drug carrier is based on alginate. And: shell m = cross-linking coating the target agent, with the electrospinning operation bar in the taste hook, the rule of the drug carrier 'can enhance the drug carrier; & sustained release and the stability of the effect, the efficacy of the invention . The electrospinning method for manufacturing a pharmaceutical carrier comprises coating a target agent with colloidal particles of alginate, and the alginate is dissolved in a physiological solvent without adversely affecting the target agent itself, and is applicable to various biomedical materials or drugs. The coating of the compound has the effect of safe use. The electrospinning method for producing a drug carrier according to the present invention is a method for producing a shape difference by a divalent cation dissociation condition, and the application characteristics of the various agents are exerted as a sustained release effect to match the (four) policy of the agent. Expand the efficacy of the pharmaceutical application level. Although the above-mentioned preferred embodiment of the present invention is disclosed, it is not intended to be a part of the present invention, and it is still within the scope of the present invention to make various changes and modifications to the above embodiments without departing from the spirit of the present invention. The scope of the invention is therefore defined by the scope of the appended claims. —14 — 201138874 [Simplified description of the drawings] Fig. 1 is a flow chart showing the steps of the electrospinning manufacturing method of a pharmaceutical carrier of the present invention. Fig. 2 is a schematic diagram showing the power supply step of the electrospinning manufacturing method of the present invention. Fig. 3 is a graph showing the relationship between the electric field strength and the particle size of the carrier in the electrospinning method for a pharmaceutical carrier. Figure 4 a
第4b圖 第5a圖 第5b圖 第5c圖 第5d圖 第5e圖 本發明之藥物载體之掃描式電顯圖。 本發明之藥物载體之又一掃描式電顯圖 本發明之藥物細之電顯圖。 本發明之_龜之又1顯圖。 ^月之藥物載體之再—電顯圖。 藥物載體之再—電顯圖。 第5f圖：本發明之藥_ ^後電··。 第5g圖:本發明之藥物載體之; 第5h圖：本發明之藥物 心後再1_ 载體之乾燥後再1_ 【主要元件符號說明】 11金屬板 21開孔 23注入件 1收集盤 2發射器 22軟管 24幫浦 201138874 3 電源供應器Figure 4b Figure 5a Figure 5b Figure 5c Figure 5d Figure 5e Scanned electrographic display of the drug carrier of the present invention. A further scanning electric display of the pharmaceutical carrier of the present invention is a fine electrogram of the drug of the present invention. The turtle of the present invention has another 1 picture. ^Re-electrographic display of the drug carrier of the month. Re-Electrical Mapping of Drug Carriers. Figure 5f: The medicine of the present invention _ ^ after the electricity · ·. Figure 5g: the drug carrier of the present invention; Figure 5h: the drug of the present invention is further 1_ after the carrier is dried and then 1_ [main symbol description] 11 metal plate 21 opening 23 injection member 1 collection disk 2 emission 22 hose 24 pump 201138874 3 power supply