JP2008194379A - Nanoparticle device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a device retaining the dispersion state of nanoparticles even in air, in a device allowing a user to inhale the nanoparticles consisting of a medical agent by respiration. <P>SOLUTION: This nanoparticle device allowing the user to inhale the nanoparticles consisting of the medical agent by respiration is formed by covering the both faces of a nanofiber sheet, which is so fixed as to enable the falling of the nanoparticles by permeating exhalation individually, with matrix sheets. The nanofiber sheet is preferably a multilayer nanofiber sheet formed by superposing a plurality of sheets, the nanofiber sheet is disposed on the both sides of the matrix sheet and the both front/back faces are covered with the matrix sheets. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a device for aspirating nanoparticles comprising a drug by respiration.

Inhalation preparations are preparations used for the treatment of respiratory diseases, but in recent years, methods for administering insulin particles by inhalation have been developed for the treatment of systemic diseases such as diabetes.
In the future, various types of drugs are expected to be developed as inhalants for other systemic diseases.
The particle size of the inhalant used in the actual market is 2 to 5 μm, and it is designed to be deposited mainly from bronchi to bronchiole.
Smaller particles with a diameter of 500 nm to 2 μm are mainly deposited in the alveoli and are thought to be phagocytosed by alveolar macrophages.
Smaller particles (500 nm or less) are considered to directly enter blood vessels, and inhalants using such nanoparticles can be used for the treatment of all diseases such as diabetes and hypertension.
However, when such fine particles are formed, they are very easily aggregated in a gas, and it has been impossible to supply fine particles in the body unless they are dispersed in a solvent.
In other words, it is ideal to suck nanoparticles by exhalation, but it has been impossible to realize.

    In view of such circumstances, an object of the present invention is to provide a device in which nano / micro particles can be maintained in a dispersed state even in air.

  The nanoparticle device of the invention 1 is characterized in that both sides of a nanofiber sheet fixed so as to be removable by exhaled breath through which the nanoparticles are individually permeated are covered with a matrix sheet.

  The nanoparticle device of the invention 2 is the nanoparticle device of the invention 1, wherein the nanoparticle device is a multilayer nanofiber sheet in which a plurality of the nanofiber sheets are stacked.

  The nanoparticle device of the invention 3 is characterized in that, in the nanoparticle device of the invention 1, the nanofiber sheet is arranged on both surfaces of the matrix sheet, and both the front and back surfaces are covered with the matrix sheet.

  The nanoparticle device of the invention 4 is the nanoparticle device of any of the inventions 1 to 3, wherein the matrix sheet is gauze.

  The nanoparticle device of the invention 5 is characterized in that, in the nanoparticle device of any one of the inventions 1 to 4, the entire shape is formed like a mask.

  The nanoparticle device of the invention 6 is characterized in that in the nanoparticle device of any of the inventions 1 to 5, the entire outer surface is covered with a sealing film.

According to Invention 1, the nanoparticles were inhaled without agglomeration.
Although the reason cannot be grasped | ascertained strictly, since the nanoparticle is being fixed to the nanofiber sheet, aggregation of particle | grains does not arise at this stage. Moreover, since the dropout is due to exhalation, it will be scattered in the same direction at the same time as the dropout, and it is thought that aggregation of the nanoparticles is prevented by this scattering.
In addition, the matrix sheet that covers both sides makes the flow of exhalation permeating the nanofiber sheet close to parallel flow, making it easier to ensure parallel movement of the nanoparticles, and this also seems to prevent aggregation. It is.

  According to the invention 2, even when the density of the nanoparticles fixed to each nanofiber sheet is reduced to prevent aggregation at the time of fixing, it is possible to suck the nanoparticles having a necessary density.

  According to the invention 3, when a plurality of nanofiber sheets are used as in the invention 2, the gaps between the nanofiber sheets can be maintained, so that the aggregation of the nanoparticles between the nanofiber sheets hardly occurs.

  According to the invention 4, since easy-to-obtain gauze was used for the matrix sheet, the productivity could be improved.

  According to the fifth aspect of the present invention, since the mask is formed, it is possible to facilitate the suction over time.

  According to the invention 6, it is possible to eliminate the risk of nanoparticles scattering due to the flow of outside air when not in use.

A drug made into nano / micro particles is deposited on the nano / micro fiber to form an inhalation device.
The nanofiber sheet on which the nanoparticle drug is adsorbed is sandwiched between matrix sheets such as gauze and the outside is covered with a protective film (FIG. 1).
The nanofiber sheet is a carrier for nanoparticles and also functions as a filter that prevents the nanoparticles from being inadvertently attached to the outside.
Moreover, the mechanical strength of the device is improved and the handling becomes easy by sandwiching between the matrix sheets.
A protective film made of a sealing film prevents desorption and scattering of nanoparticles when not in use, and suppresses deterioration (oxidation and moisture absorption) of the nanoparticles.
In this device, it was confirmed that the drug nanoparticles adhering to the nanofibers were desorbed by airflow.
A metal, an inorganic, an organic polymer, or the like can be used for the nanofiber as a nanoparticle carrier.
Specific examples include chemical fibers (bioabsorbable metals such as magnesium alloys, other metal fibers such as stainless steel and titanium, inorganic fibers such as glass and carbon, bioabsorbable polymers such as polyvinylpyrrolidone and polylactic acid, other polyesters, Artificial polymers such as polyamide), natural fibers (animal and plant fibers such as cotton and silk, mineral fibers such as wollastonite), regenerated fibers (polysaccharides such as cellulose and dextran, and polypeptides such as collagen, sericin and albumin) The regenerated fiber used and derivatives and composites thereof are used.
The diameter of the fiber is in the range of several tens of nanometers to several tens of micrometers.
Although depending on the material constituting the fiber, when the fiber diameter is small, oxidation degradation, mechanical strength, and the like become problems.
When the diameter is large, a surface area sufficient to adsorb particles cannot be secured.
Moreover, when the fiber diameter was large, the tendency for the adsorption amount of a nanomicroparticle to fall was confirmed.
The particle diameter of the drug is in the range of several tens of nm to several μm.
The size is defined by the drug applied.
For example, a particle size of 1 to several μm is used for respiratory disease treatment, and a particle size of tens to hundreds of nm is used for systemic administration.

1. A nanofiber sheet is prepared by spraying a polymer solution, which is a raw material of the fiber, from a nozzle by electrospinning.
2. The drug nanoparticles are deposited on the nanofiber sheet using a spray drying method.
Creation method 1. An aluminum foil was covered with a cotton mat, and a 10 wt% PVP (poly (vinyl pyrrolidone) ethanol solution) was sprayed thereon with an electrospinning apparatus to prepare a nanofiber sheet.
(Electrospinning conditions: temperature; room temperature, DC voltage; 15 kV, distance between nozzle and collector; 20 cm) It was confirmed that a nonwoven fabric having a structure in which nanofibers having a diameter of about 600 nm were intertwined was obtained.
2. The nanofiber sheet prepared above was placed on a filter of a spray drying apparatus, sprayed with a 1 wt% creatine aqueous solution, and dried.
(Spray drying conditions: nozzle outlet temperature; 180 ° C., Asspirator speed; 35%; Pump speed; 5%) It was confirmed that the spherical particles of Creatine (particle size: 300 nm-2 μm) were dispersed on the PVP nanofibers. (Figure 3)
3. Nitrogen gas is allowed to flow at the same air velocity (5 L / min) as that of human inspiration to the created Createine-supported nanofiber sheet, and the Creatine nanoparticles on the nanofiber are selectively desorbed, leaving only the nanofiber. It was confirmed. (Fig. 4)

4. Method of sandwiching the nanofiber sheet and gauze and fixing the state (1) Create a nanofiber sheet alone, then coat one side of the nanofiber sheet with gauze, and then adsorb nano / microparticles. A method of coating the other surface with gauze after dispersing,
(2) One possible method is to form nanofibers on one side of the gauze, adsorb and disperse the nano / micro particles, and then coat the other side of the nanofibers with gauze.
In order to prevent particles from being inadvertently scattered from the gap between the nanofiber sheet and the gauze, the sheet and the two sheets of gauze may be bonded together on all four sides.

5. Specific Examples of Sealing Film As the sealing film, artificial polymers such as polypropylene and polystyrene, natural polymers such as cellulose and dextran, and derivatives and composites thereof are used.
In order to suppress photodegradation of particles, a light-shielding film or the like may be used.
In order to suppress the oxidation of the particles, an oxygen absorbent or the like may be applied to the film.
In order to suppress the moisture absorption of the particles, a dehydrating agent or the like may be applied to the film.
The film is adhered to the gauze by the adhesiveness of the polymer material itself, or the film is coated with a coating agent to adhere.
In order to prevent particles from being inadvertently scattered from the gap between the nanofiber sheet and the gauze, the sheet, the two sheets of gauze, and the sealing film may be bonded to all four sides.

FIG. 5 shows an example in which two nanofiber sheets are arranged in a stacked manner.
A PVP nanofiber sheet is prepared on the cotton mat (gauze) surface by an electrospinning device, drug particles are adsorbed on the sheet simultaneously with the generation by a spray drying device, and the nanofiber sheet is prepared by an electrospinning device. A specific example is shown below.
How to make. An aluminum foil was covered with a cotton mat, and a 10 wt% PVP (poly (vinyl pyrrolidone) ethanol solution) was sprayed thereon with an electrospinning apparatus to prepare a nanofiber sheet.
(Electrospinning conditions: temperature; room temperature, DC voltage; 15 kV, distance between nozzle and collector; 20 cm) It was confirmed that a nonwoven fabric having a structure in which nanofibers having a diameter of about 600 nm were intertwined was obtained.
2. The nanofiber sheet prepared above was placed on a filter of a spray drying apparatus, sprayed with a 1 wt% creatine aqueous solution, and dried.
(Spray drying conditions: nozzle outlet temperature; 180 ° C., Asspirator speed; 35%; Pump speed; 5%) It was confirmed that the spherical particles of Creatine (particle size: 300 nm-2 μm) were dispersed on the PVP nanofibers.
3. The nanofiber sheet prepared above was again coated on aluminum foil, and a 10 wt% PVP ethanol solution was sprayed thereon with an electrospinning apparatus, and the nanofiber sheet was coated thereon.

FIG. 6 shows an example in which two nanofiber sheets are stacked via gauze.
A cotton mat (gauze) was coated on a structure in which two nanofiber sheets prepared according to Example 3 were stacked.
In this case, the arrangement state of the cotton mat (gauze) and the nanofiber sheet is fixed by a physical entanglement effect.

FIG. 7 shows an example of a device shaped into a square shape, which is effective when a sufficient amount of medicine can be administered by inhalation by instantaneous inspiration instead of long-term inspiration as in a mask.
When a sufficient amount of drug particles is administered by aspiration by instantaneous expiration, the nanofiber sheet to which the particles are attached needs to have a large area.
The amount of drug particles that can be applied depends on the length of the exhalation flow path (the thickness of the nanofiber sheet).
When the nanofiber sheet is arranged perpendicularly to the inhalation direction, a sufficient flow path for exhalation cannot be secured (flow path length = thickness of the nanofiber sheet). When the nanofiber sheet is arranged in parallel to the inhalation direction, the particles present in the exhalation flow path increase depending on the length of the nanofiber sheet.

The nanoparticles can exist stably in the dispersion solvent. In the absence of a dispersion solvent, the nanoparticles aggregate to form large aggregates, and the properties of individual nanoparticles are lost. This proposal will be a new method for retaining nanoparticles under solvent-free conditions and may be a new technology in the pharmaceutical field, especially in the field of inhalation devices.
According to the present invention, since the nanoparticulate drug can be aspirated, the oral preparation or the injection can be changed to an inhalant.
As an effect, receiving a drug without infusion can be a means of reducing medical costs in terms of medical economy.
In addition, since it is easy to use, lightweight, and easy to dispose, it can be quickly spread to many regions including developing countries and disaster-stricken areas, and the effect can be demonstrated at an early stage.

The partially expanded perspective view which shows the structure of the mask-shaped inhalation device of Example 1. The front view which shows the whole mask of Example 1 Photomicrograph showing Creatine particles deposited on the PVP nanofibers of Example 1. The microscope picture which shows the fiber sheet after exposing the nanofiber sheet of the state of FIG. 3 to the nitrogen gas airflow with a flow rate of 5 L / min. The partially expanded perspective view which shows the principal part of Example 2. The partial expansion perspective view which shows the principal part of Example 3 The perspective view which shows the device of Example 4.

Claims (6)

A device for sucking nanoparticles made of a drug by respiration, wherein both sides of the nanofiber sheet fixed so as to be removable by exhaled breath through which the nanoparticles are individually permeated are covered with a matrix sheet Nanoparticle device. The device for nanoparticles according to claim 1, wherein the device is a multilayer nanofiber sheet in which a plurality of the nanofiber sheets are stacked. 2. The nanoparticle device according to claim 1, wherein the nanofiber sheet is disposed on both sides of the matrix sheet, and both the front and back surfaces are covered with the matrix sheet. 4. The nanoparticle device according to claim 1, wherein the matrix sheet is gauze. The device for nanoparticles according to any one of claims 1 to 4, wherein the entire shape is formed like a mask. 6. The nanoparticle device according to claim 1, wherein the entire outer surface is covered with a sealing film.