JP2015107387A - Frequently and easily detachable microneedle base - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for easily detaching a microneedle array chip from an applicator.SOLUTION: Between a magnetic force response part arranged at a chip for a base for constructing a microneedle array and a magnetic force generation part arranged at an applicator, attachment is executed utilizing magnetic force. In the case of detachment from the applicator, by demagnetizing the magnetic force generation part arranged at the applicator or physically detaching the chip for the base, the microneedle array chip can be easily detached from the applicator.

Description

In the present invention, when a plurality of base chips (hereinafter referred to as microneedle array chips) in which microneedles are constructed in an array are continuously administered using a single applicator, they can be easily and frequently detached. The present invention relates to a microneedle base.

Microneedles are finely sized needles that do not feel pain when stabbed into the skin, and physically protect the stratum corneum that is located on the outermost side of the skin and protects the body from the entry of bacteria and viruses from the outside world. This is a formulation technique that improves the absorption rate of drugs and cosmetic compounds that cannot be absorbed even when transdermally administered by conventional techniques.

A microneedle array with multiple microneedles organized like a forest is a type of metal microneedle with a hollow structure that injects medicinal liquids or made of biodegradable polymer materials such as polylactic acid. It may be a microneedle (Non-Patent Document 1). Furthermore, soluble microneedles based on water-soluble substances have also been developed. That is, the target substance can be transdermally administered by holding the target substance using a water-soluble substance as a base and inserting it into the skin and then dissolving the base with the moisture in the skin. . For example, a microneedle based on chondroitin sulfate and hyaluronic acid is disclosed (Patent Document 1).

Since the microneedle is a minute protrusion, when it is administered, the skin cannot be efficiently punctured unless it collides perpendicularly to the skin. Therefore, an applicator is disclosed (Patent Document 2).

When the microneedle array chip is fixed to the applicator, the applicator must be discarded every time one chip is administered, which is economically inefficient. However, when treating a local disease such as skin, it is necessary to administer a plurality of microneedle array chips to a plurality of locations.

Japanese Patent No. 4913030 Japanese Patent Application 2010-201875 James C. Birchall, Chapter 18. Stratum corneum bypassed or removed in Enhancement in DrugDelivery.edited by Elka Touitou and Brian W. Barry, pp. 337-351, CRC Press, 2007.

An object of the present invention is to provide a method for easily detaching a plurality of microneedle array chips from an applicator.

When using the magnetic force between the magnetic force response part arranged on the base chip for constructing the microneedle array and the magnetic force generation part arranged on the applicator, and detaching the microneedle array chip from the applicator In this case, the microneedle array chip can be easily attached to and detached from the applicator by demagnetizing the magnetic force of the magnetic force generating portion arranged in the applicator or by physically removing the base chip.

That is, the present invention is a method for easily attaching and detaching to / from an applicator provided with a magnetic force generation portion by imparting magnetic force responsiveness to a chip for a substrate on which a microneedle array is constructed.

The above chip for base adds magnetic responsiveness to a molded body composed of a porous plate made of plastic such as polyethylene, polymethyl methacrylate, polyvinyl chloride and chlorinated polyethylene-styrene resin, and a non-water-soluble tablet excipient. It is a thing.

The above-mentioned chip for base is a tablet prepared by blending iron powder.

The above-mentioned base chip is a two-layer tablet, which is a two-layer tablet prepared by blending iron powder in a layer opposite to the layer constituting the microneedle array.

In one certain form, the said chip | tip for base | substrates is obtained by tableting the excipient | filler for tablets.

Among them, a preferable base chip is a tablet obtained by adding a magnetically responsive component to a molded article made of a water-insoluble tablet excipient or a two-layer tablet partially added. This is because it is excellent in productivity and suitable for pharmaceutical manufacturing processes such as sterilization. The tablet excipient may be a composition containing a plurality of components. Preferred excipients for tablets include cellulose acetate, crystalline cellulose, cellulose derivatives, chitin and chitin derivatives. Examples of the magnetic force responsive component include iron powder.

The substrate chip made of the tablet excipient may be produced by the same method as the tablet. For example, a magnetically responsive component is mixed with a tablet excipient and placed in a mortar of a tableting machine, and tableted with an appropriate tableting pressure using a punch. The dimensions of the base chip are appropriately adjusted by increasing or decreasing the diameter of the die, the filling amount of the tablet excipient, and the tableting pressure.

The particle system of iron powder, which is a magnetically responsive component added to the substrate chip, is preferably 1 to 500 micrometers, more preferably 10 to 200 micrometers. This is because when the particle size of the iron powder is increased, the mortar and pestle are damaged during tableting.

The shape of the base chip is, for example, a disk shape having a diameter of 5 to 50 mm, preferably 10 to 35 mm, and a thickness of 1 to 10 mm, preferably 2 to 5 mm. Moreover, it does not necessarily have to be a disk shape, and may be a quadrangular or rectangular shape. The hardness of the base chip does not change substantially when a fine needle of a percutaneous absorption preparation is pierced into the skin, and when a fine needle of a percutaneous absorption preparation is pierced into the skin by applying an impact force There is no particular limitation as long as it does not collapse. Place a disk-shaped tablet base chip on a metal cylinder with an outer diameter of 2.0 cm, an inner diameter of 1.2 cm, and a height of 2.0 cm, and use a digital force gauge (FGP-50, Nidec Symposium). When the collapse strength is measured by attaching a conical attachment to the tip, the collapse strength of the base chip is 10 to 50 N in one embodiment. In this case, the thickness of the sample used for the measurement is 2.0 mm.

The strength of the magnetic force required for the magnetic force generating part applied to the applicator is determined by the microneedle array chip holding part of the applicator when the microneedle array chip having the magnetic response part is held on the applicator and administered to the skin. Although it will not specifically limit if it is a grade which does not drop out from, it is 1mT-500mT practically, Preferably it is 5mT-300mT, More preferably, it is 20mT-200mT.

The present invention is not limited to a soluble microneedle array chip, and may be a metal or plastic microneedle array chip.

By using the method of the present invention, the microneedle array chip can be easily detached from the applicator.

Specific embodiments will be described below with reference to examples. Of course, the present invention is not limited to the following examples.

Example 1
About 0.5 g of 100: 10: 5 blend of cellulose acetate, hydroxypropyl cellulose and iron powder (average particle diameter 100 micrometers, JIP MG270H, JFE Steel) on a mortar of a single punch (Ichihashi Seiki, HANDTAB100) The tablet which becomes the chip | tip for base | substrates of diameter 1.5cm and thickness about 2.0mm with the tableting pressure of about 10 kN was produced. A viscous liquid was prepared by adding 250 microliters of purified water to 200 mg of chondroitin sulfate and stirring well. This viscous liquid was applied onto a female mold having 225 inverted conical pores having a depth of about 500 microns per square centimeter and an opening diameter of about 300 microns, and filled into the female mold under pressure conditions. . After drying, sodium chondroitin sulfate viscous liquid was again applied to the female mold and filled into the female mold under pressure. A viscous liquid prepared by adding 100 microliters of purified water to 50 mg of sodium chondroitin sulfate was applied to a chip for a substrate, covered on a female mold, and dried under pressure. The microneedle array chip was obtained as a tablet having magnetic responsiveness in which 225 microneedles were constructed in an array by pulling the base chip away from the female mold after 6 hours.

(Example 2)
First, about 0.30 g of a 100: 10: 5 blend of cellulose acetate, hydroxypropylcellulose and iron powder was placed in a single-punch tablet mill. Next, about 0.25 g of a 100: 10 mixture of cellulose acetate and hydroxypropylcellulose is placed on top of it, and a base chip having a diameter of 1.5 cm and a thickness of about 2.0 mm is obtained with a tableting pressure of about 10 kN. A layered tablet was made. A viscous liquid was prepared by adding 250 microliters of purified water to 200 mg of chondroitin sulfate and stirring well. This viscous liquid was applied on a female mold having 225 inverted conical pores having a depth of about 500 microns per square centimeter and an opening diameter of about 300 microns. A female mold was filled under pressure. After drying, sodium chondroitin sulfate viscous liquid was again applied to the female mold and filled into the female mold under pressure. A viscous liquid prepared by adding 100 microliters of purified water to 50 mg of sodium chondroitin sulfate was applied to a chip for a substrate, covered on a female mold, and dried under pressure. After 6 hours, the microchip array chip was obtained as a two-layer tablet having magnetic response, in which 225 microneedles were constructed in an array by pulling the base chip away from the female mold.

There is a need for a method of easily detaching a microneedle array chip from an applicator.

According to the present invention, when using a magnetic force between the magnetic force response part arranged on the chip for the base for constructing the microneedle array and the magnetic force generation part arranged on the applicator, and when separating from the applicator, The microneedle array chip can be easily attached to and detached from the applicator by demagnetizing the magnetic force of the magnetic force generating portion disposed in the applicator or by physically removing the base chip.

In other words, the present invention provides a microchip in which microneedles are constructed in an array on a base, which is easily detachable from an applicator provided with a magnetic force generation portion by imparting magnetic force responsiveness to the base chip. A needle array chip,
Provided is a microneedle array chip, wherein the base chip is a tablet produced by blending iron powder into a tablet excipient and tableting.

  In one certain form, the said excipient | filler for tablets is at least 1 type selected from the group which consists of a cellulose acetate, a crystalline cellulose, a cellulose derivative, chitin, and a chitin derivative.

  In one certain form, the said chip | tip for base | substrates is a 2 layer tablet produced by mix | blending iron powder with the layer on the opposite side of the layer which comprises a microneedle array.

  In one certain form, the magnetic strength of the magnetic force generation part provided to the applicator is 1 mT to 500 mT.

  In addition, the present invention provides a microneedle array in which microneedles are constructed in an array on a base that can be easily detached from and applied to an applicator provided with a magnetic force generation portion by imparting magnetic responsiveness. A chip base chip,
  Provided is a chip for a substrate, which is a tablet produced by blending iron powder into a tablet excipient and tableting.

Claims (5)

In this method, magnetic force responsiveness is imparted to the substrate chip on which the microneedle array is constructed, so that it can be easily detached from the applicator to which the magnetic force generating portion is imparted. The chip for a substrate according to claim 1 is a molded body comprising a porous plate of plastic such as polyethylene, polymethyl methacrylate, polyvinyl chloride and chlorinated polyethylene-styrene resin, and a water-insoluble tablet excipient. Magnetic response is added. The base chip according to claim 1 is a tablet prepared by blending iron powder. The base chip according to claim 3 is a two-layer tablet, and is a two-layer tablet prepared by blending iron powder in a layer opposite to the layer constituting the microneedle array. The strength of the magnetic force required for the magnetic force generating portion applied to the applicator according to claim 1 is practically 1 mT to 500 mT, preferably 5 mT to 300 mT, more preferably 20 mT to 200 mT.