TW201905218A - A metal tip with a large surface area - Google Patents

Abstract

The objective of this patent is to achieve a new class of drug detected and released needle with large surface to absorbs and release the indicator or drug. The approach is to explore the tungsten and aluminum novel sub-micron or nano needle. This approach is expect to provide both tiny needle but large needle surface area to significantly boost the achievable the sensitively of drug detected and released. New electrochemical processes including electro-polished, electro-etched, and anodization are introduced to assistance a tiny needle and nanotube film under ambient conditions, thereby enabling low-cost and mass production of the needle.

Description

 Metal tip with large surface area  

This patent relates to a metal needle tip having a large surface area, which can adsorb a large amount of dyes, detection reagents, or drugs, and can be applied to precise micro-detection or micro- and rapid drug release applications.

The conventional drug release method is a method for slowly dissolving the drug in the body and transporting the drug to the affected part along with the blood flow. In order to make those methods practical, it is not enough to improve the drug, and it is necessary to develop a high drug. Molecular materials, or matrix materials such as inorganic materials, the smaller the diameter of the drug particles, the better the absorption of the drug. From this point of view, the size of the drug plus the matrix material must be controlled to a few micrometers.

The transdermal drug delivery system is a new route of administration that overcomes the shortcomings of the above two modes of administration. It not only avoids the possibility of loss of oral efficacy due to digestion of the gastrointestinal system, but also reduces the pain and infection caused by subcutaneous injection. risks of. However, since the outermost layer of human skin is the stratum corneum, it is a very important protective barrier of the human body, and it is hydrophobic and has a negative charge, thus causing macromolecular drugs and hydrophilic drugs to be difficult to penetrate, which is a transdermal drug delivery system. The biggest obstacle to development.

The conventional drug release patch structure comprises: a support substrate, the surface of which comprises a plurality of protruding support shafts; a biodegradable carrier formed of a biodegradable polymer material and disposed on the support shaft, coated The drug in the biodegradable carrier, the biodegradable carrier can be swelled in the skin and then degraded to release the drug coated in the biodegradable carrier at a rate of 1%/day to 99%/day. In the skin.

At present, most of the commercially available microneedle patches are made of metal or tantalum. The user must bear the risk of infection caused by microneedle breakage and repeated use of microneedles, which may also cause harm to biomedical waste. And commercial patches often need to be in contact with the skin for a long time, and may also cause allergic reactions such as itching and redness of the skin. In addition, the microneedle patches currently developed are mostly rapid release pharmaceutical dosage forms, and there are no long-acting dosage forms for sustainable release drugs.

In order to improve the above disadvantages, the present patent proposes a sub-micron or nano-needle tip having a metal-based porous oxide film as a surface for providing a large surface area drug release function.

The metal needle tip having a large surface area of the invention comprises: a metal wire, a needle tip formed by electrolytic polishing and electrolytic etching on one end of the wire, and the porous tip attached to the surface of the needle tip after the needle tip is subjected to anodization treatment. Oxide film, the size of the tip is between the micron and nanometer grades, wherein the metal wire comprises aluminum wire, tungsten wire, tin wire, titanium wire, zirconium wire, molybdenum wire, and the porous oxide film includes aluminum oxide film and tungsten oxide film. a tin oxide film, a titanium oxide film, a zirconium oxide film, a molybdenum oxide film, a porous oxide film having micropores of a nanometer or submicron order, the needle tip comprising a single needle tip or a plurality of needle tips, the plurality of needle tips comprising an array type The tip of the needle has the function of adsorbing and releasing dyes, drugs, and detecting agents.

The purpose of electrolytic polishing is to make the metal and alloy into a very smooth mirror gloss, which is often used for industrial mirror polishing. Metals such as pure aluminum, copper, and silver are extremely soft, or metals such as tungsten, zirconium, and molybdenum are extremely hard, and it is difficult to remove the surface scratches by conventional mechanical polishing. In addition, the chemical polishing method is The test piece is polished by reacting the active anion in the solution, such as sulfate ion, acid chloride ion, etc., on the surface of the test piece, although the chemical polishing method can remove the scratch on the surface of the substrate, but is chemically polished. After the method, the surface of the substrate tends to remain active ions in the solution. Therefore, it is not suitable for samples requiring extremely high surface cleanliness, and the electropolishing method can meet the requirements of extremely high surface cleanliness. After the surface of the sample is dissociated, the metal ions are dissolved into the electrolyte, so that the surface of the substrate can be kept extremely clean after the reaction is completed. The metal tip of the invention has a large surface area, and the substrate may be aluminum wire, tungsten wire, tin wire, titanium wire, zirconium wire or molybdenum wire. In order to obtain a flat surface for some hard or soft materials, electrolysis Polishing is the best choice.

Anode treatment has long been defined as a mature traditional industry, its main applications such as surface corrosion resistance, coating, adhesion, decoration, electrical insulation, surface plating, wear resistance and other surface modification applications, due to the porous anodized film The structure of the anode film is subsequently subjected to a sealing treatment step, so that the anode film can have a beautiful and multi-colored dense film when applied. In recent years, due to the development of nanotechnology, the tube diameter, tube length, and tube density of the anodized film tube or nanotube structure are technically more complete. The simple anode treatment technology provides a low-cost and fast mass production process, which can be practically applied to product development requiring large surface area per unit area, such as dye-sensitized solar cells, thermal conductive sheets, and thermal insulation sheet components. The anodizing technology, in response to the demand of industrial products, has been applied to the vacuum chamber of the evaporation equipment in recent years for the surface corrosion resistance, abrasion resistance, impact resistance, and high temperature resistance of heavy industrial structures. The coating absorption layer of the part, or the barrier layer in the integrated circuit, with the development of the most popular heat dissipation materials, heat insulation materials, green building materials, and solar cell industry, the anodizing technology with automatic production characteristics is bound to become One of the processes of various industries.

When an active element such as aluminum, tungsten, tin, titanium, zirconium, molybdenum or the like is placed in a specific electrolyte and the appropriate anode treatment parameters are controlled, the formed oxide film has a regular cell or nanotube structure. The interface between the end of the nanotube and the metal substrate forms a hemispherical barrier layer, wherein the components of the nanotube and the barrier layer are metal oxides, the diameter of the nanotube, the tube density, the wall thickness, The length of the tube depends on the anode processing parameters. Taking aluminum anode treatment as an example, the aluminum anodized film is also known as anodic aluminum oxide (AAO), anodic alumina nanoholds (AAN), anodic alumina membrane (AAM), or porous anodic alumina (PAA). The aluminum anode treatment is mainly performed by 2Al ^{+ 3} +3H ₂ O→Al ₂ O ₃ +6H ⁺ reaction, therefore, it is necessary to control the pH below 4, that is, under the condition of acidic solution, and the applied voltage should be higher than -1.8V (SHE) or more. in the H ⁺ by _{^{H + + H + → H 2}} , to generate hydrogen, this hydrogen from inside Al ₂ O ₃ Al ₂ O ₃ to escape, and cause of the porous alumina is formed, and therefore, the control of the hydrogen evolution At the rate, the pores formed inside the alumina can be controlled to become an aluminum anodized film having a uniform pore diameter. When the aluminum is anodized, an aluminum oxide (Al ₂ O ₃ ) oxide layer is formed on the surface, and the oxide layer grows upwards in a hexagonal hole at the beginning of growth, and the arrangement of atoms around the hexagonal hole gradually increases with time. The arrangement of the disorder, so the hole gradually turns into a circular hole, and the change in the size of the aperture can be expressed by C=mV, where C: aperture size (nm), V: anode processing voltage (V), m: Constant (2~2.5).

Hereinafter, each of the embodiments of the metal needle tip having a large surface area according to the present invention will be described in detail using the second to fourth figures . In the description of the drawings, the same elements or elements having the same function are denoted by the same reference numerals, and the description thereof will not be repeated.

 [Example 1]  

Aluminum tip with large surface area

In this example, the pure aluminum wire whose surface has been acid-washed and alkali-washed is electropolished to make the pure aluminum wire have a smooth surface, and includes three steps: electrolytic polishing, electrolytic etching, and anodizing. (1) Electropolishing : The conditions of electrolytic polishing are: 5~20% perchloric acid (HClO ₄ ) + 5~20% monobutyl ether ethylene diester (CH ₃ (CH ₂ ) ₃ OCH ₂ CH ₂ OH) +85 ~95% ethanol (C ₂ H ₆ O), electrolyte temperature is 2~40 °C, electrolysis voltage is 5~50 volts, electropolishing time is 1~5 minutes, better electropolishing operation condition is 15% perchlorination Acid (HClO ₄ ) + 15% monobutyl ether ethylene diester (CH ₃ (CH ₂ ) ₃ OCH ₂ CH ₂ OH) + 70% ethanol (C ₂ H ₆ O), electrolyte temperature is 25 ° C, electrolysis voltage is 40 volts, electropolishing time is 1.5 minutes. The electropolished aluminum wire is then subjected to an electrolytic etching process to obtain an aluminum needle tip. (2) Electrolytic etching : The conditions of electrolytic etching are: 5-20 vol.% nitric acid (HNO ₃ ), and the electrolyte temperature is 2-40 ° C. The electrolysis voltage is 5~50 volts, the electropolishing time is 0.5~5 minutes, the preferred electrolytic etching operation condition is 6vol.% nitric acid (HNO ₃ ), the electrolyte temperature is 25 ° C, the electrolysis voltage is 30 volts, electropolishing time of 1 minute, as shown in the obtained photograph as a second tip of FIG. (3) Anode treatment : The electrolyte treated by the anode is mainly sulfuric acid, phosphoric acid, or oxalic acid. Using 1~10 vol.% (volume percent) sulfuric acid aqueous solution as electrolyte, plus 5~25 volts DC voltage, anode treatment time 0.1~1 hour, electrolyte temperature 0~15 °C, can make the surface of metal aluminum wire react to produce holes A thin film of aluminum oxide having a pore structure of 10 to 30 nm. Using 1~5wt.% (% by weight) aqueous solution of oxalic acid as electrolyte, adding 20~60V DC voltage, anode treatment time 0.1~1 hour, electrolyte temperature 0~25°C, can make the surface of metal aluminum wire react to produce holes The aluminum oxide film of 30~100nm pore structure uses 1~3vol.% (volume%) phosphoric acid aqueous solution as electrolyte, plus 100~200 volts DC voltage, anode treatment time 0.1~1 hour, electrolyte temperature is -8~15 °C, the surface of the aluminum wire can be reacted to produce a film of aluminum oxide having a pore structure of 100-500 nm. The photomicrograph is shown in the third figure . After electropolishing, electrolytic etching, and anodizing, a porous aluminum oxide film having a large surface area on the surface of the metal aluminum tip is coated, and the needle tip is inserted into the colored dye to observe that the color-saturated dye is adsorbed on the needle tip. The actual photograph after the needle tip adsorbs the dye is shown in the fourth figure .

 [Example 2]  

A tungsten tip with a large surface area

In this example, the pure tungsten wire whose surface has been acid-washed and alkali-washed is subjected to electrolytic polishing to make the pure tungsten wire have a smooth surface, and comprises three steps: electrolytic polishing, electrolytic etching, and anodizing. (1) Electropolishing : The conditions of electrolytic polishing are: 5~25wt.% sodium hydroxide (NaOH) +10~40wt.% sodium potassium tartrate (NaKC ₄ H ₄ O ₆ ), the electrolyte temperature is 2~40°C, The electrolysis voltage is 5~50 volts, the electropolishing time is 1~5 minutes, and the preferred electropolishing operation condition is 8wt.% sodium hydroxide (NaOH) + 15wt.% sodium potassium tartrate (NaKC ₄ H ₄ O ₆ ), The electrolyte temperature was 10 ° C, the electrolysis voltage was 20 volts, and the electropolishing time was 3 minutes. The electropolished tungsten wire is then subjected to an electrolytic etching process to obtain an aluminum tip, and (2) electrolytic etching : electrolytic etching conditions are: 5 to 25 wt.% sodium hydroxide (NaOH), and the electrolyte temperature is 2 to 40. °C, the electrolysis voltage is 5~30 volts, the electropolishing time is 0.5~5 minutes, the preferred electrolytic etching operation condition is 10wt.% sodium hydroxide (NaOH), the electrolyte temperature is 5 °C, and the electrolysis voltage is 10 volts. The electropolishing time was 1 minute. (3) Anode treatment : The electrolyte treated with anodizing is mainly oxalic acid. Using 1~5wt.% (% by weight) aqueous solution of oxalic acid as electrolyte, plus 20~60V DC voltage, anode treatment time 0.1~1 hour, electrolyte temperature 0~25°C, can make the surface of metal tungsten wire react to produce holes A tungsten oxide film having a pore structure of 30 to 100 nm. After electropolishing, electrolytic etching, and anodizing, a porous tungsten oxide film having a large surface area on the surface of the gold-tungsten needle tip is coated, and the needle tip is inserted into the colored dye to observe that the color-saturated dye is adsorbed on the needle tip.

 [Example 3]  

Array type aluminum tip with large surface area

In this example, the surface of the arrayed aluminum column is subjected to electrolytic polishing of the surface-washed aluminum column to provide a smooth surface comprising three steps: electrolytic polishing, electrolytic etching, and anodizing. (1) Electropolishing : The conditions of electrolytic polishing are: 5~20% perchloric acid (HClO ₄ ) + 5~20% monobutyl ether ethylene diester (CH ₃ (CH ₂ ) ₃ OCH ₂ CH ₂ OH) +85 ~95% ethanol (C ₂ H ₆ O), electrolyte temperature is 2~40 °C, electrolysis voltage is 5~50 volts, electropolishing time is 1~5 minutes, better electropolishing operation condition is 15% perchlorination Acid (HClO ₄ ) + 15% monobutyl ether ethylene diester (CH ₃ (CH ₂ ) ₃ OCH ₂ CH ₂ OH) + 70% ethanol (C ₂ H ₆ O), electrolyte temperature is 25 ° C, electrolysis voltage is 40 volts, electropolishing time is 1.5 minutes. The electrolytically polished array of aluminum pillars is then subjected to an electrolytic etching process to obtain an array of aluminum needle tips. (2) Electrolytic etching : electrolytic etching conditions are: 5-20 vol.% nitric acid (HNO ₃ ), and the electrolyte temperature is 2~40°C, the electrolysis voltage is 5~50 volts, the electropolishing time is 0.5~5 minutes, the preferred electrolytic etching operation condition is 6vol.% nitric acid (HNO ₃ ), the electrolyte temperature is 25 ° C, and the electrolysis voltage is 30 Volt, electropolishing time is 1 minute. (3) Anode treatment : The electrolyte treated by the anode is mainly sulfuric acid, phosphoric acid, or oxalic acid. Using 1~10 vol.% (volume percent) sulfuric acid aqueous solution as electrolyte, adding 5~25 volts DC voltage, anode treatment time 0.1~1 hour, electrolyte temperature 0~15 °C, the surface of the array aluminum needle tip can be reacted The aluminum oxide film having a pore structure of 10 to 30 nm is formed. Using 1~5wt.% (% by weight) aqueous solution of oxalic acid as electrolyte, adding 20~60V DC voltage, anode treatment time 0.1~1 hour, electrolyte temperature 0~25°C, can make the surface of metal aluminum wire react to produce holes The aluminum oxide film of 30~100nm pore structure uses 1~3vol.% (volume%) phosphoric acid aqueous solution as electrolyte, plus 100~200 volts DC voltage, anode treatment time 0.1~1 hour, electrolyte temperature is -8~15 °C, the surface of the aluminum wire can be reacted to produce a film of aluminum oxide having a hole structure of 100-500 nm. After electrolytic polishing, electrolytic etching, and anodic treatment, the surface of the aluminum tip of the array has a large surface area of porous alumina film, as shown in the fifth figure, the color of the dye is observed by inserting the tip into the colored dye. On the tip of the needle.

10‧‧‧Metal substrate

11‧‧‧Porous oxide layer

12‧‧‧Aluminum metal substrate

13‧‧‧Porous alumina layer

First figure A structural diagram of a metal tip with a large surface area, (a) schematic, (b) microstructure.

The second figure shows the appearance of the aluminum tip after electrolytic polishing and electrolytic etching.

The third figure is anodized to form a porous aluminum oxide film on the surface of the needle tip.

Figure 4 The surface of the aluminum needle can absorb colored dyes.

Claims (10)

 A metal needle tip having a large surface area, the structure comprising: a metal wire, a tip of the wire formed by electropolishing and electrolytic etching, and the needle tip is subjected to anodization to obtain a porous oxide film attached to the surface of the needle tip.    A metal needle tip having a large surface area, the tip structure of which is a metal substrate, and the outer surface thereof is covered with an oxide layer.    A metal tip having a large surface area as claimed in claim 1, wherein the metal wire comprises an aluminum wire, a tungsten wire, a tin wire, a titanium wire, a zirconium wire, and a molybdenum wire.    A metal tip having a large surface area as claimed in claim 1, wherein the porous oxide film comprises an aluminum oxide film, a tungsten oxide film, a tin oxide film, a titanium oxide film, a zirconium oxide film, and a molybdenum oxide film.    A metal tip having a large surface area as claimed in claim 1, wherein the pore size of the porous oxide film can be controlled by an anode treatment voltage value.    A metal tip having a large surface area as claimed in claim 1, wherein the porous oxide film has micropores of a nanometer or submicron order.    A metal tip having a large surface area as claimed in claim 1, wherein the needle tip comprises a single needle tip or a plurality of needle tips.    A metal tip having a large surface area as claimed in claim 5, wherein the plurality of needle tips comprise an array type needle tip.    A metal tip having a large surface area as claimed in claim 1, the needle tip having a function of adsorbing and releasing a dye, a drug, and a detecting agent.    A metal tip having a large surface area as claimed in claim 1, wherein the size of the tip is between the micron and nanometer grades.