JP5145514B2 - Ophthalmic spray supply device - Google Patents

Description

  The present invention relates to an ophthalmic spray supply device that atomizes an ophthalmic drug to form atomized drug particles and sprays the generated drug solution particles to the surface of a patient's eyeball. More specifically, the present invention generally relates to an ultrasonic mesh type. The present invention relates to an ophthalmic spray supply apparatus configured to spray and supply eye drops onto a patient's eyeball surface using an atomization mechanism called an atomization mechanism.

  Ophthalmic drugs prescribed in the ophthalmic field are used for the treatment and prevention of eye diseases. Usually, this eye drop is liquid. Therefore, an ophthalmic method is generally used for administration of eye drops to patients. The eye drop method is an eye drop administration method in which a liquid eye drop accommodated in a bottle is dropped from a nozzle provided at the tip of the bottle toward the surface of the eyeball.

  In the above-mentioned eye drop method, liquid eye drops are made into droplets and supplied dropwise onto the surface of the eyeball. Therefore, in conventional eye drops, the amount of eye drops actually required (generally 1 [μl] to several [μl] ] In excess of the amount (approximately 30 [μl] to 50 [μl]) is dripped toward the eyeball surface. For this reason, there has been a problem that the over-supplied eye drops overflow from the eyes without being retained on the surface of the eyeball, or are absorbed into the body via the lacrimal duct. This problem not only causes an economic loss in that it cannot efficiently administer relatively expensive eye drops, but in certain types of eye drops, the eye drops overflow from the eyes and enter the skin. Adhesion causes the skin to be inflamed, or administration of more than the required amount of eye drops causes undesired side effects. Furthermore, when the eye drop method is used, the eye drops overflow from the eyes as described above, and the patient needs to face the face vertically upward when applying the eye drops.

  In order to solve the above problems, an ophthalmic drug administration method (hereinafter referred to as a spray supply method) in which the eye drops are made into mist-like drug solution particles and sprayed toward the eyeball surface has been studied. If this spray supply method is established, it is possible not only to prevent an excessive supply of the chemical solution, but also to avoid the above-mentioned troublesomeness, so that it is possible to realize a highly efficient and easy administration of the eye drops.

  As a literature in which a specific ophthalmic spray supply device that realizes the above-described spray supply method is being studied, for example, Japanese Patent Laid-Open No. 62-142110 (Patent Document 1) and Japanese Patent Publication No. 8-502688 (Patent Document 2). ) Etc.

  In the ophthalmic spray supply device disclosed in Patent Document 1, charged mist-like liquid chemical particles are produced by applying an electric field generated by a high voltage generator to ophthalmic drugs discharged from a tapered spray nozzle. The charged chemical liquid particles are deposited on the surface of the eyeball by electrostatic action (the mist-like chemical liquid particles adhere to the eyeball surface).

  On the other hand, in the ophthalmic spray supply device disclosed in Patent Document 2, a medicinal solution is dripped by dripping a medicinal solution from above onto a mesh member having a large number of micropores and vibrating the mesh member. Particles are generated, and the generated chemical liquid particles are placed on an airflow generated by a blower fan and sprayed toward the eyeball surface, whereby the chemical liquid particles are deposited on the eyeball surface.

Further, although different from the above-described ophthalmic spray supply device, an inhaler is known as a spray supply device that atomizes a chemical solution to form atomized chemical liquid particles and administers this to a patient. The inhaler is used for treatment and prevention of respiratory diseases, and drug particles sprayed from the inhaler are taken into the body through the oral cavity or nasal cavity of the patient. As an atomization mechanism employed in this inhaler, there is an atomization mechanism generally called an ultrasonic mesh type. The atomization mechanism includes a horn unit and an ultrasonic vibrator including a vibration unit as a drive source for vibrating the horn unit, and a mesh member disposed to face the tip of the horn unit of the ultrasonic vibrator. The chemical solution supplied between the mesh member and the horn part is extruded from the micropores provided in the mesh member using ultrasonic vibration to form atomized chemical solution particles. Incidentally, as a document disclosing an inhaler provided with this ultrasonic mesh type atomizing mechanism, there is, for example, Japanese Patent Application Laid-Open No. 2001-149473 (Patent Document 3).
JP-A-62-142110 JP-T 8-50289 JP 2001-149473 A

  In the above Patent Documents 1 and 2, sufficient examination has not been made on the administration efficiency of the sprayed ophthalmic drug. For example, in Patent Document 1, a device has been devised to increase the deposition rate on the eyeball by using the electrostatic force by charging the generated chemical liquid particles, but as to what degree of deposition rate can actually be realized. No disclosure has been made. Further, Patent Document 2 only discloses that chemical liquid particles are deposited on an eyeball by placing them on an air stream, and no disclosure is made as to how to achieve a high deposition rate. . In particular, in the case of the ophthalmic spray supply apparatus disclosed in Patent Document 2, it is easily imagined that the drug particles are scattered in a wide range on an air stream, and it is very difficult to increase the administration efficiency in the first place. it is conceivable that.

  The present invention has been devised in view of the above-described present situation, and an object thereof is to provide a novel ophthalmic spray supply apparatus capable of administering a very small amount of eye drops with high administration efficiency.

  The present inventors have obtained knowledge that an ultrasonic mesh type atomization mechanism is suitable as an atomization mechanism to be applied to the ophthalmic spray supply apparatus. In order to deposit a very small amount of eye drops on the surface of the eyeball with high administration efficiency, it is important to provide directivity to the liquid chemical particles sprayed from the atomizing part. This is a finding obtained by paying attention to the fact that a mesh type atomization mechanism can be realized relatively easily.

  In the ultrasonic mesh type atomization mechanism, the fine particle inertia force is applied to the chemical liquid by the vibration of the ultrasonic vibrator and the mesh, and the liquid force is sprayed by the inertia force as a thrust. Therefore, chemical liquid particles can be sprayed without generating an air flow. In addition, since the inertial force is uniformly applied to the generated chemical liquid particles in the axial direction of the ultrasonic vibrator (that is, the normal direction of the mesh member), the directivity can be controlled with high accuracy. . Therefore, if an ultrasonic mesh type atomization mechanism is used as the atomization mechanism, it is possible to efficiently spray a very small amount of drug particles toward the eyeball surface, and the deposition rate adopts another atomization mechanism. Compared to the case, it will be dramatically improved.

  In establishing a spray supply method using an ultrasonic mesh type atomization mechanism, the present inventors extract various parameters that affect the deposition rate of drug particles on the surface of the eyeball by conducting various experiments. At the same time, we examined how much these parameters affect the deposition rate. As a result, the present inventors have found that the deposition rate of liquid chemical particles on the surface of the eyeball depends on the inertia parameter, and in particular, greatly depends on the Stokes number, which is one of the inertia parameters. Based on this finding, the present inventors have completed the present invention.

An ophthalmic spray supply device according to the present invention atomizes an ophthalmic drug in an atomizing unit to form atomized liquid chemical particles, which are sprayed toward the patient's eyeball surface. Is a plate-like mesh member including a large number of micropores reaching from one main surface to the other main surface, a horn portion disposed opposite to one main surface of the mesh member, and a vibration source for vibrating the horn portion And an ultrasonic transducer including a vibrating part. Then, the ophthalmic spray supply device according to the present invention is configured such that the Stokes number Stk at the position where the surface of the eyeball to which the chemical liquid particles are sprayed is arranged is ρ, the density of the chemical liquid particles is ρ, and the average radius of the chemical liquid particles at the above position is Where r is the average velocity of the chemical liquid particles at the position u, the viscosity constant of the air is μ, and the distance from the other principal surface of the mesh member to the position is L, Stk = (ρ × r ² × u) / (μ × L) ≧ 0.09. Here, the Stokes number is a parameter representing the degree of inertial force of particles, and is a so-called dimensionless number. In addition, the position where the eyeball surface is disposed is a position where the eyeball surface is intended to be disposed at the position in the ophthalmic spray supply apparatus.

  When the ultrasonic mesh type atomization mechanism is adopted as the atomization mechanism, it is possible to easily control the size of the generated chemical liquid particles by adjusting the size of the micropores provided in the mesh member. In addition, by adjusting the voltage applied to the ultrasonic transducer, it is possible to easily control the speed of the generated chemical liquid particles. Therefore, in adjusting the Stokes number so as to satisfy the above conditions, adopting an ultrasonic mesh atomizing mechanism as the atomizing mechanism of the ophthalmic spray supply device is more effective than adopting other atomizing mechanisms. The adjustment is easy, and it can be understood from this point that the ultrasonic mesh type atomization mechanism is suitable as the atomization mechanism of the ophthalmic spray supply apparatus.

  In the ophthalmic spray supply apparatus according to the present invention, the diameter of the micropores provided in the mesh member is preferably 3 [μm] or more and 20 [μm] or less.

  In the ophthalmic spray supply apparatus according to the present invention, the ophthalmic spray supply apparatus further includes a cylindrical guide portion that defines a lead-out path for guiding the liquid chemical particles sprayed from the atomizing unit. In this case, it is preferable that the guide portion is provided with an open end against which the patient's face is pressed. In that case, it is preferable that the length from the atomization part to the opening end is 3 [mm] or more and 30 [mm] or less.

  Moreover, in the ophthalmic spray supply apparatus based on the said invention, it is preferable that the said mesh member has the curved shape or bending shape which becomes convex toward the said horn part side.

  By utilizing the above-described ophthalmic spray supply device according to the present invention, it is possible to very easily administer a very small amount of ophthalmic drug with high administration efficiency. Therefore, it is possible to administer the eye drops at a low cost without bothering the patient, and a useful spray eye drop method that contributes to the treatment and prevention of eye diseases in the ophthalmic field can be realized.

  Prior to specific description of the embodiments of the present invention, the contents and results of experiments conducted by the present inventors will be described.

<Measurement of physical properties of chemicals>
First, the present inventors measured the physical property values of a chemical solution used as an eye drop. As physical property values of the chemical solution to be measured, density, viscosity and surface tension were selected, and the average value was obtained by performing measurement a plurality of times. The medicinal solution measured was 100 μg / ml NGF solution, Linderon (registered trademark) -A eye drop [manufactured by Shionogi Seiyaku Co., Ltd.], cyclosporin A eye drop, BSS eye drop (oxyglutathione eye perfusion / cleaning liquid) [Kyoto Prefectural Medical Department] University offer], physiological saline [manufactured by Otsuka Pharmaceutical Co., Ltd.], Soft Santare (artificial tear-type eye drop) [manufactured by Santen Pharmaceutical Co., Ltd.]. NGF solution is used in corneal regenerative medicine, Linderon (registered trademark) -A eye drop is an anti-inflammatory agent for postoperative management of ophthalmic treatment, and cyclosporine A eye drop is used for the treatment of dry eye allergy complications. It is an immunosuppressant used. Further, the BSS eye drops are used as a dispersion of an NGF solution or an ophthalmic solution after surgery. The results are shown in Table 1 below.

  As can be seen from Table 1, it was confirmed that the above six types of chemical solutions had a significant difference in physical property values other than density.

<Examination of the effect of difference in viscosity and surface tension on atomization>
Next, when the chemical solution was atomized using an ultrasonic mesh atomizing mechanism, the degree of influence of the difference in the viscosity and surface tension of the chemical solution on the atomization of the chemical solution was examined. . Based on Weber's atomization theory, the chemical properties (density ρ ₁ , viscosity μ ₁ and surface tension σ), the diameter D _{0 of the} liquid column formed upon atomization, and the diameter D _{ae of} the generated chemical liquid particles Is represented by the following formula (1).

D _ae / D ₀ = 1.88 × (1+ (3 μ ₁ / (D ₀ × ρ ₁ × σ) ^1/2 )) (1)

  As understood from the above formula (1), when liquid column splitting occurs in the chemical liquid during atomization to form chemical liquid particles, the particle diameter of the generated chemical liquid particles is influenced by the physical property value. However, since there is no great difference in the physical property value in the chemical solution having a low chemical concentration, there is a great difference in the diameter of the chemical particle generated based on the physical property value of the chemical solution among the six types of chemical solutions described above. It is thought that there is nothing. Therefore, in general ophthalmic drugs, although a significant difference occurs in the physical property value, it can be said that the influence of the difference in the physical property value on the atomization characteristics is low. Based on the above findings, physiological saline was mainly used as a chemical solution in the verification tests conducted thereafter.

<Configuration of ultrasonic mesh atomization mechanism used for verification test>
In the verification test described below, an ultrasonic mesh atomization mechanism as shown in FIG. 1 was employed as an atomization mechanism that atomizes a chemical solution to form atomized chemical solution particles. FIG. 1 is a schematic diagram showing a configuration of an ultrasonic mesh atomizing mechanism used in the verification test, and FIG. 2 is an enlarged perspective view of a part of the mesh member shown in FIG. 1 cut out and enlarged. First, with reference to FIG. 1 and FIG. 2, the ultrasonic mesh type atomization mechanism used in this verification test will be described in detail.

  As shown in FIG. 1, the ultrasonic mesh atomization mechanism 2 mainly includes an ultrasonic transducer 10 and a mesh member 20. The ultrasonic transducer 10 includes a vibration unit 11 as a vibration source and a horn unit 12 connected to the vibration unit 11. The horn unit 12 has an atomizing surface 12a, and the mesh member 20 is disposed to face the atomizing surface 12a. As shown in FIG. 2, the mesh member 20 is a plate-like member having a large number of minute holes 21 reaching from one main surface 20 a to the other main surface 20 b. An AC power supply 14 is electrically connected to the ultrasonic transducer 10. In addition, the atomization part is comprised by the atomization surface 12a provided in the front-end | tip of the horn part 12 of the ultrasonic transducer | vibrator 10, and the mesh member 20 arrange | positioned facing this atomization surface 12a.

  FIG. 3 is a schematic cross-sectional view for explaining the principle by which the chemical solution is atomized in the atomizing section in the ultrasonic mesh atomizing mechanism shown in FIG. 1. Next, with reference to this FIG. 3, the principle by which the chemical | medical solution is atomized in the atomization part in the ultrasonic mesh type atomization mechanism shown in FIG. 1 is demonstrated.

  In the ultrasonic mesh atomization mechanism shown in FIG. 1, the vibration unit 11 is driven by the AC power source 14, so that the vibration unit 11 and the horn unit 12 are in the axial direction of the ultrasonic transducer 10 (in the direction of arrow A in the figure). ) Start to vibrate. The vibration of the ultrasonic transducer 10 also propagates to the mesh member 20 disposed opposite to the horn portion 12, and a gap is formed between the atomized surface 12 a of the horn portion 12 and the main surface 20 a of the mesh member 20. Will come to be.

  As shown in FIG. 3, the chemical solution 50 that has entered the gap formed between the atomizing surface 12 a of the horn portion 12 and the main surface 20 a of the mesh member 20 is a distance between the mesh member 20 and the horn portion 12. Is compressed and pushed out from the micro holes 21 of the mesh member 20. At that time, the liquid column splitting described above occurs in the extruded chemical liquid 50, and mist-like chemical liquid particles 51 are generated. Since the generated chemical liquid particles 51 are given a fine particle inertia force, the chemical liquid particles are sprayed toward the space from the other main surface 20b of the mesh member 20 using the inertia force as a thrust.

<Test content of verification test>
This verification test verifies what parameters affect the deposition rate of drug particles on the surface of the eyeball when the ophthalmic spray is supplied using an ultrasonic mesh atomization mechanism. It is. FIG. 4 is a model diagram of a test apparatus used in this verification test. FIG. 5 is a model diagram of a test apparatus for measuring the diameter of the generated chemical liquid particles. FIG. 6 is a model diagram of the test apparatus for measuring the speed of the generated chemical liquid particles. Next, the contents of this verification test will be described in detail with reference to FIGS.

  As shown in FIG. 4, when measuring the deposition rate, the ultrasonic mesh type atomization mechanism 2 is used to form physiological saline as the drug solution 50 into the mist-like drug solution particles 51, which are sprayed toward the eyeball model 110. It was decided to supply. Here, as the eyeball model 110, a flat pseudo-corneal model 112 made of rubber was applied to the surface of a flat glass slide 111 and silicon oil 113 was applied to the surface.

  The calculation of the deposition rate is based on the concentration of the chemical solution supplied to the ultrasonic mesh atomization mechanism 2 and the concentration of the chemical solution atomized by the ultrasonic mesh atomization mechanism 2 and supplied to the eyeball model 110 by spraying. Was performed by measuring. The physiological saline used as a sample was colored with ink so that the concentration could be measured using a spectrophotometer. In calculating the concentration, a calibration curve showing the relationship between the concentration and absorbance prepared in advance was used.

  As the mesh member 20 of the ultrasonic mesh type atomizing mechanism 2, two types of those having a diameter of the micropore 21 of 3.5 [μm] and that of 4.8 [μm] were used. The total number of micro holes 21 provided in the mesh member 20 was approximately 7000. The driving voltage of the ultrasonic transducer 10 was set in two stages, DC6 [V] and DC8 [V]. In addition, since the ultrasonic transducer 10 is driven by applying an AC voltage, actually, the DC voltage is boosted by the boosting circuit to convert the power, and is applied to the ultrasonic transducer 10 as an AC voltage. It was decided. Further, the distance L between the ultrasonic mesh atomizing mechanism 2 and the eyeball model 110 was set in three stages of 10 [mm], 20 [mm], and 30 [mm]. Further, the amount of the sample supplied to the ultrasonic mesh atomizing mechanism 2 was set to 1 [μl] corresponding to the amount of a very small amount of the chemical liquid required for the ophthalmic spray. As a result of the verification test, the time required to atomize the sample of 1 [μl] was about ˜0.4 [s].

  Further, as shown in FIG. 5, the diameter of the chemical liquid particles is measured by irradiating the chemical liquid particles 51 sprayed from the ultrasonic mesh atomizing mechanism 2 with a pulse laser beam using a laser irradiation device 201. Was performed by photographing using an imaging device (digital camera) 211. More specifically, the laser irradiation apparatus 201 is connected to a PC (personal computer) 200 via the control unit 207, and the imaging apparatus 211 is connected to the PC 200, and the laser irradiation apparatus 201 and the imaging apparatus 211 are synchronized. Thus, the chemical liquid particles were photographed, and the diameter of the chemical liquid particles was measured by analyzing only the image of the focused chemical liquid particles from the photographed image. In order to optimize the conditions for photographing, the laser irradiation device 201 is provided with a filter 202, condensing lenses 203 and 205, and an optical fiber 204 as an optical system, and the imaging device 211 has an optical system. The objective lens 212 was attached.

  In addition, as shown in FIG. 6, the measurement of the speed of the chemical liquid particles is performed by using two laser beams with a predetermined time interval for the chemical liquid particles 51 sprayed from the ultrasonic mesh atomizing mechanism 2. This was performed by irradiating a pulsed laser beam and photographing this using an imaging device (digital camera) 211. More specifically, the laser irradiation apparatus 221 is connected to a PC (personal computer) 200, and the imaging apparatus 211 is connected to the PC 200, and the laser irradiation apparatus 221 and the imaging apparatus 211 are synchronized, thereby imaging chemical liquid particles. The movement distance of the chemical liquid particles was calculated from images taken at regular intervals using two pulsed laser beams, and the speed of the chemical liquid particles was measured based on this. In order to optimize the conditions for photographing, a diffusion plate 222 as an optical system is attached to the laser irradiation device 201, and an objective lens 212 as an optical system is attached to the imaging device 211.

<Test results and evaluation of verification tests>
In general, the deposition phenomenon of fine particles includes an electrical factor and a Brownian motion of particles. However, when the particle radius exceeds 1 μm, the inertial force is dominant for the deposition phenomenon. According to the verification test, it is confirmed that the diameter of the chemical liquid particles generated when the ultrasonic mesh atomization mechanism as described above is used is several [μm] to several tens [μm]. From the results, it can be said that the inertial force is dominant over the deposition phenomenon when the eye drops are sprayed. Therefore, the present inventors evaluated the deposition phenomenon based on the Stokes number Stk, which is one of inertia parameters, as the deposition parameter.

  The Stokes number Stk is a dimensionless number indicating the degree of the inertial force of the particle, and is the particle density ρ, the particle radius r, the particle velocity u, the air viscosity constant μ, and the distance from the position where the inertial force is applied. It is represented by the following formula (2) using L.

Stk = (ρ × r ² × u) / (μ × L) (2)

  Based on the result of this verification test, the density ρ is the density of the drug particle, the radius r of the particle is the geometric mean aerodynamic diameter of the drug particle, and the velocity u of the particle is the drug particle on the deposition surface (that is, the surface of the eyeball model). The Stokes number Stk was calculated using the velocity component in the normal direction and the distance L as the distance from the atomizing portion to the deposition surface. Then, the correlation between the value of the Stokes number thus obtained and the deposition rate of the chemical liquid particles was evaluated. FIG. 7 is a correlation diagram in which the relationship between the value of the square root of the Stokes number and the deposition rate of chemical liquid particles is plotted on the coordinates based on the test result of this verification test. As can be understood from FIG. 7, it can be said that there is a certain correlation between the value of the Stokes number and the deposition rate of the chemical liquid particles.

  In addition, the inventors separately performed a simulation of the correlation between the deposition rate and the Stokes number by performing a kinetic analysis. The simulation result is shown together with the correlation diagram of FIG. 7 showing the test result of the verification test. As can be understood from FIG. 7, it can be said that the test result and the simulation result are well matched, and from this, it can be said that the generality of the test result and the simulation result is ensured.

  From the above test results and simulation results, it was derived that the following approximate expression (3) is established between the deposition rate η and the Stokes number Stk.

η = 1-exp (34.1 × Stk−52.5 × Stk ^1/2 +12.1) (3)

  From the above approximate expression (3), in order to obtain a deposition rate of 50% or more, the Stokes number should be about 0.092 (about 0.09 when rounded down to the third decimal place), and 80% In order to obtain the above deposition rate, the Stokes number should be about 0.112 (about 0.11 when rounded down to the third decimal place), and in order to obtain a deposition rate of 90% or more, The Stokes number should be about 0.128 (about 0.12 when rounded down to the third decimal place), and in order to obtain a deposition rate of 98% or more, the Stokes number is about 0.176 (decimal point It was found that it should be about 0.17) or more when truncated at the third place.

As described above, the inventors focused on the Stokes number as one of the inertia parameters, but also examined inertia parameters other than the Stokes number. As the inertial parameters, when the density of the chemical liquid particles is ρ [kg / m ³ ], the radius of the chemical liquid particles is r [m], and the initial velocity u ₀ [m / s] of the chemical liquid particles is The parameter P [kg / s] represented by

P = ρ × r ² × u ₀ (4)

The parameter P is a parameter that does not take into account the distance from the atomizing portion, but in view of the fact that the initial velocity u ₀ of the chemical liquid particles is taken into account, the degree of inertial force of the chemical liquid particles is similar to the Stokes number. It can be used as an indicator. The present inventors have confirmed that the deposition rate exceeds 98% when the parameter P takes a value of 1.3 × 10 ⁻⁷ [kg / s] or more.

<Embodiment>
Based on the results derived from the verification tests described above, specific examples for realizing highly efficient ophthalmic drug administration in an ophthalmic spray supply apparatus equipped with an ultrasonic mesh-type atomization mechanism will be described below. It describes as.

  FIG. 8 is a schematic cross-sectional view showing the configuration of the ophthalmic spray supply apparatus according to the embodiment of the present invention. As shown in FIG. 8, the ophthalmic spray supply device 1 according to the present embodiment mainly includes a casing 31, an ultrasonic mesh atomizing mechanism 2, a guide member 34, and a biasing spring 36. .

  An ultrasonic mesh atomizing mechanism 2 is disposed at a predetermined position of the housing 31. The ultrasonic mesh atomizing mechanism 2 has the same configuration as that shown in FIG. 1, and mainly includes an ultrasonic transducer 10, a mesh member 20, and an AC power supply 14. The housing 31 has a cylindrical connecting portion 32 that protrudes outward from its side surface. An opening is provided in the side wall of the housing 31 corresponding to the bottom wall of the connection portion 32, and the tip of the horn portion 12 of the ultrasonic transducer 10 is connected to the outside of the housing 31 through the opening. And it arrange | positions so that it may expose inside the connection part 32. FIG. The mesh member 20 is disposed inside the connection portion 32. The mesh member 20 is disposed such that one main surface thereof faces the atomizing surface 12 a of the horn portion 12. In addition, although illustration is abbreviate | omitted, between the opening part of the housing | casing 31 and the horn part 12, the sealing process for ensuring watertightness is performed.

  As the vibrating part 11 of the ultrasonic transducer 10, for example, a piezoelectric element made of PZT, lithium niobate, or the like can be used. Moreover, as the horn part 12 of the ultrasonic transducer | vibrator 10, the thing made from ceramics, the thing made from stainless steel, the thing made from titanium, etc. can be utilized, for example. On the other hand, as the shape of the horn portion 12, a so-called conical type, step type, exponential type, or the like can be used. The horn unit 12 shown in FIG. 8 corresponds to a so-called step type.

  The mesh member 20 may be manufactured by electroforming (so-called electroforming) using a metal such as nickel as a base material, manufactured by molding ceramics, or manufactured by etching silicon.

  A cylindrical guide member 34 is attached to the connection portion 32 of the housing 31. The guide member 34 has a step portion at a predetermined position on its inner peripheral surface. The biasing spring 36 is disposed inside the connecting portion 32, and one end thereof is fitted into the above-described stepped portion, and the other end is in contact with the mesh member 20. Thereby, the mesh member 20 is pressed and fixed to the atomizing surface 12 a of the horn portion 12 by the urging force of the urging spring 36.

  The space inside the cylindrical guide part constituted by the connection part 32 and the guide member 34 becomes a lead-out path for the chemical liquid particles sprayed from the atomization part. Then, the end of the guide member 34 opposite to the end connected to the connecting portion 32 becomes an open end 34b against which the patient's face is pressed, and by pressing the periphery of the eye against this open end, The patient's eyes are arranged on the opening surface 34 a of the guide member 34.

  FIG. 9 is a diagram schematically showing a state in which the eye drops are sprayed toward the eyeball surface using the eye drop spray supply apparatus according to the present embodiment. In FIG. 9, the specific configuration of the ophthalmic spray supply apparatus 1 is omitted, and only the ultrasonic mesh atomizing mechanism 2 and the eyeball 100 are illustrated.

  When using the ophthalmic spray supply apparatus 1, first, the housing 31 is tilted so that the opening surface 34 a of the guide member 34 attached to the housing 31 faces upward, and the guide member 34 passes through the opening surface 34 a of the guide member 34. A very small amount (for example, about 1 [μl] to several [μl]) of a chemical solution is dropped toward the atomizing portion. The dropped chemical solution is held by the atomizing section due to its surface tension. Thereafter, the tilted casing 31 is returned to the state shown in FIG. 8, and the patient's face is pressed toward the open end 34b. Then, the ultrasonic transducer 10 is driven. The posture of the patient at that time may be a sitting position or a standing posture. In any case, the posture is such that the face is oriented almost horizontally.

  As already described, by driving the ultrasonic transducer 10, the chemical liquid is pushed out from the micro holes 21 of the mesh member 20 by the vibration of the horn part 12 and the mesh member 20, and the liquid chemical is split in the extruded chemical liquid. It occurs and mist-like chemical liquid particles 51 are generated. Since the generated chemical liquid particles 51 are given a fine particle inertia force, as shown in FIG. 9, the chemical liquid particles 51 are sprayed from the other main surface 20b of the mesh member 20 toward the space by using the inertia force as a thrust. Then, the sprayed drug particles 51 are supplied toward the eyeball surface.

  In addition, in the ophthalmic spray supply apparatus 1 according to the present embodiment, a fine particle inertia force is imparted to the chemical liquid particles by adopting the ultrasonic mesh atomization mechanism 2, and the chemical liquid particles are applied to the surface of the eyeball based on the inertia force. Therefore, it is not necessary to generate an airflow in the lead-out path. However, when the patient presses the face against the open end 34b of the guide member 34 and the lead-out path becomes a completely sealed space, the flow of the chemical liquid particles may not be smooth depending on the spraying conditions. Therefore, in such a case, it is good also as providing a communicating hole as needed in the surrounding wall of the connection part 32 or the guide member 34, and maintaining the state where a derivation | leading-out path is not sealed completely by this communicating hole.

In the ophthalmic spray supply apparatus 1 according to the present embodiment, the Stokes number Stk at the position where the eyeball surface to which the chemical liquid particles are sprayed is arranged is ρ, the density of the chemical liquid particles is ρ, and the average radius of the chemical liquid particles at the above position is Where r is the average velocity of the chemical liquid particles at the position u, the viscosity constant of the air is μ, and the distance from the other principal surface of the mesh member to the position is L, Stk = (ρ × r ² × u) / (μ × L) ≧ 0.09. Specifically, the above condition is satisfied by adjusting the size of the opening diameter of the microhole 21 provided in the mesh member 20 and the applied voltage for driving the ultrasonic transducer 10. Has been. This is because the Stokes number Stk depends on the radius r and the velocity u of the chemical liquid particles, and the adjustment of the radius r of the chemical liquid particles is the size of the opening diameter of the micropores 21 provided in the mesh member 20. This is because it is possible to adjust the velocity u of the chemical liquid particles and the applied voltage for driving the ultrasonic transducer 10.

Preferably, the opening diameter of the micro holes 21 provided in the mesh member 20 is 3 [μm] to 20 [μm]. The applied voltage for driving the ultrasonic transducer 10 varies depending on the specific configurations of the vibration unit 11 and the horn unit 12, but is considered to be preferably approximately AC 20 [V] to AC 30 [V]. . By adjusting the opening diameter of the minute hole 21 and the voltage applied to the ultrasonic transducer 10 within these ranges, the above-described condition that the Stokes number Stk at the position where the eyeball surface is disposed is 0.09 or more is satisfied. It will be. The distance L from the atomizing portion to the eyeball surface is preferably adjusted to 3 [mm] or more and 30 [mm] or less (more preferably about 10 [mm]). By setting the distance L within the above range, the above-described conditions can be realized more reliably. In the ophthalmic spray supply apparatus 1 according to the present embodiment, the distance L is generally determined by the length L _{A of the} lead-out path (the distance from the main surface 20b of the mesh member 20 to the open end 34b of the guide member 34). Because of the configuration, the length L _A of the lead-out path may be adjusted to 3 [mm] or more and 30 [mm] or less (more preferably about 10 [mm] to 20 [mm]). It should be noted that a spray condition is realized such that the Stokes number Stk is 0.09 or more at any point where the distance L is 3 [mm] or more and 30 [mm] or less, and the eyeball surface is arranged at the point. If the ophthalmic spray supply apparatus is configured, the ophthalmic spray supply apparatus in which at least the deposition rate is maintained at 50% or more can be obtained. In addition, if the Stokes number Stk at the above point is adjusted to 0.11, 0.12, 0.17, the ophthalmic solution in which the deposition rate is kept at 80% or more, 90% or more, and 98% or more, respectively. It can be set as a spray supply device.

  By using the ophthalmic spray supply apparatus as described above, it is possible to administer a very small amount of ophthalmic drug with high administration efficiency. Based on the result of the above-described verification test, it is possible to deposit almost the entire amount of the chemical solution supplied to the atomizing section on the eyeball surface, and it is possible to spray and supply the eyedrop to the eyeball surface with almost no loss. In addition, it is possible to administer ophthalmic drugs in a very short time. Overflow of chemicals from the eyes, the risk of side effects due to overdose, and the face faced vertically upward, which were the problems of conventional eye drops. There is no need for troubles such as necessity and generation of economic loss, and the ophthalmic drug can be administered to the patient simply and efficiently. Therefore, it is possible to realize a new and useful ophthalmic administration method that replaces the conventional eye drop method.

  By the way, if the inertial force is not applied in the direction toward the eyeball surface to the chemical liquid particles atomized by the atomization unit, the deposition rate is significantly reduced. On the other hand, since the surface of the eyeball is covered with tears, the drug particles deposited on the surface of the eyeball immediately diffuse over the entire surface of the eyeball. Therefore, when spraying ophthalmic drugs, it is important to spray the medicinal liquid particles to be sprayed with directivity toward the eyeball surface. More specifically, it is preferable to impart directivity to each of the generated chemical liquid particles so that the chemical liquid particles sprayed from the atomizing portion are sprayed in a concentrated manner at the center position on the eyeball surface. From such a viewpoint, a modified example in which the ophthalmic spray supply device in the present embodiment described above is modified will be described in detail below.

  10 and 11 are schematic cross-sectional views showing modifications of the ophthalmic spray supply device in the present embodiment described above. 10 and 11, the specific configuration of the ophthalmic spray supply apparatus is omitted, and only the ultrasonic mesh atomization mechanism 2 and the eyeball 100 are illustrated.

  In the ophthalmic spray supply apparatus shown in FIG. 10, the atomizing surface 12 a of the horn unit 12 of the ultrasonic transducer 10 is formed in a curved concave shape, and the mesh member 20 is placed on the atomizing surface 12 a side of the horn unit 12. The curved shape is convex toward the head. The curved mesh member 20 can be manufactured, for example, by bending a mesh member formed into a plate shape by the above-described electroforming (electroforming) using its rollability.

  In the curved mesh member 20 formed by such a method, it is possible to configure the extending directions of the numerous micro holes 21 to be non-parallel (more specifically, to be concentrated toward the inside). Become. Therefore, by adopting the configuration as described above, the generated medicinal liquid particles 51 are concentrated and sprayed toward the center position on the surface of the eyeball, so that the ophthalmic spray supply capable of realizing high administration efficiency. It can be a device.

  In the ophthalmic spray supply apparatus shown in FIG. 11, the mesh member 20 has a bent shape that is convex toward the atomizing surface 12 a side of the horn portion 12. The bent mesh member 20 can be manufactured, for example, by bending a mesh member formed into a plate shape by the above-described electroforming (electroforming) using its rollability.

  In the bent mesh member 20 formed by such a method, the extending directions of the numerous micro holes 21 can be configured to be non-parallel (more specifically, to be concentrated toward the inside). Become. Therefore, by adopting the configuration as described above, the generated medicinal liquid particles 51 are concentrated and sprayed toward the center position on the surface of the eyeball, so that the ophthalmic spray supply capable of realizing high administration efficiency. It can be a device.

  In addition, the said embodiment disclosed this time and its modification are illustrations in all the points, Comprising: It is not restrictive. The technical scope of the present invention is defined by the terms of the claims, and is intended to include any modifications within the scope and meaning equivalent to the terms of the claims.

It is a schematic diagram which shows the structure of the ultrasonic mesh type atomization mechanism used for the verification test. It is the expansion perspective view which cut and expanded some mesh members shown in FIG. In the ultrasonic mesh type atomization mechanism shown in FIG. 1, it is a schematic cross section for demonstrating the principle in which a chemical | medical solution is atomized in an atomization part. It is a model figure of the test apparatus used for the verification test. It is a model figure of the test apparatus for measuring the particle diameter of a chemical | medical solution particle. It is a model figure of the test apparatus for measuring the speed | velocity | rate of a chemical | medical solution particle. It is the correlation diagram which plotted on the coordinate the relationship between the deposition rate of a chemical | medical solution particle | grain, and the value of the square root of the Stokes number as an inertia parameter based on the test result of a verification test. It is a schematic cross section which shows the structure of the ophthalmic spray supply apparatus in embodiment of this invention. It is the figure which showed typically the state which is spraying toward the eyeball surface using the ophthalmic spray supply apparatus in embodiment of this invention. It is a schematic cross section which shows the modification of the ophthalmic spray supply apparatus in embodiment of this invention. It is a schematic cross section which shows the modification of the ophthalmic spray supply apparatus in embodiment of this invention.

Explanation of symbols

  DESCRIPTION OF SYMBOLS 1 Ophthalmic spray supply apparatus, 2 Ultrasonic mesh type atomization mechanism, 10 Ultrasonic vibrator, 11 Vibration part, 12 Horn part, 12a Atomization surface, 14 AC power supply, 20 Mesh member, 20a, 20b Main surface, 21 Micropore, 31 housing, 32 connection part, 34 guide member, 34a opening surface, 34b opening end, 36 biasing spring, 50 chemical liquid, 51 chemical liquid particle, 100 eyeball, 110 eyeball model, 111 slide glass, 112 pseudo corneal model , 113 silicon oil, 201, 221 laser irradiation device, 202 filter, 203, 205 condenser lens, 204 optical fiber, 207 control unit, 211 imaging device, 212 objective lens, 222 diffusion plate.

Claims (4)

An ophthalmic spray supply device that atomizes eye drops in an atomization unit to form atomized liquid chemical particles, and sprays this toward the patient's eyeball surface,
The atomizing portion includes a plate-shaped mesh member including a large number of micropores reaching from one main surface to the other main surface, a horn portion disposed opposite to one main surface of the mesh member, and the horn portion. An ultrasonic vibrator including a vibrating portion as a vibration source to vibrate,
The Stokes number Stk at the position where the surface of the eyeball to which the chemical liquid particles are sprayed is arranged is ρ, the density of the chemical liquid particles is ρ, the average radius of the chemical liquid particles at the position is r, and the average velocity of the chemical liquid particles at the position is u, where the air viscosity constant is μ, and the distance from the other principal surface of the mesh member to the position is L, Stk = (ρ × r ² × u) / (μ × L) ≧ 0. An ophthalmic spray supply device that satisfies the condition of 09.   The ophthalmic spray supply apparatus according to claim 1, wherein a diameter of the micropore provided in the mesh member is 3 [μm] or more and 20 [μm] or less. Further comprising a cylindrical guide part for defining a lead-out path for guiding the chemical liquid particles sprayed from the atomizing part,
The guide portion has an open end against which a patient's face is pressed,
The ophthalmic spray supply apparatus according to claim 1 or 2, wherein a length from the atomization portion to the opening end is 3 [mm] or more and 30 [mm] or less.   The ophthalmic spray supply apparatus according to any one of claims 1 to 3, wherein the mesh member has a curved shape or a bent shape that is convex toward the horn portion side.

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