WO2005092489A1

WO2005092489A1 - Particularization condition determining method and device, and particle manufacturing method and apparatus

Info

Publication number: WO2005092489A1
Application number: PCT/JP2005/004444
Authority: WO
Inventors: Tomonori Kawakami; Mitsuo Hiramatsu; Tokio Takagi
Original assignee: Hamamatsu Photonics K.K.
Priority date: 2004-03-26
Filing date: 2005-03-14
Publication date: 2005-10-06
Also published as: JP4593144B2; JP2005279328A

Abstract

A manufacturing apparatus (1A) comprises a determining device (10) for determining the particularization condition including a process chamber (3) containing a solvent (4) and a liquid (2) to be processed and composed of material particles (5) of a substance to be particularized, a laser light source (20) for irradiating the liquid (2) with a laser beam, and a controller (25) for controlling the laser beam irradiation condition. The determining device (10) includes an emitted light measuring instrument (11) for measuring the emitted light emitted in particularization caused when the liquid (2) is irradiated with a laser beam and an analyzer (15) for determining the laser beam irradiation condition for the liquid (2) depending on the emission characteristic determined from the results of the measurement of the emitted light. Thus, particularization condition determining method and device capable of preferably controlling the condition of irradiation of the liquid with a laser beam while judging that particularization by laser beam irradiation has occurred and a particle manufacturing method and apparatus are realized.

Description

Method and apparatus for determining micronization conditions, and method and apparatus for producing fine particles

Technical field

The present invention relates to a method and a device for determining fine-particle conditions for finely dividing a substance, and a method and a device for producing fine particles using the same.

Background art

[0002] Particulation of a substance results in an extremely large surface area. For this reason, there is an advantage that by making the substance into fine particles, properties inherent to the substance can easily appear. In the case of a substance that is hardly soluble or insoluble, the fine particles are quasi-solubilized in a solvent such as water due to the formation of fine particles (the fine particles are suspended in the solvent, but the light scattering is low). For the sake of simplicity, it is also possible to make it look like a pseudo-soluble one).

[0003] As such a method of forming fine particles, there is a method disclosed in Patent Document 1 (Japanese Patent Application Laid-Open No. 2001-113159). Here, a method of producing fine particles of an organic pigment or a condensed aromatic polycyclic compound by irradiating a laser beam is disclosed. Non-Patent Documents 13 to 13 also describe fine particles of organic compounds by laser light irradiation. Patent Document 1: JP 2001-113159 A

Non-Patent Document 1: Y. Tamaki et al., Tailoring nanoparticles of aromatic and dye molecules by excimer laser irradiation ", Applied Surface Science Vol. 168, p.85-88 (2000)

Non-Patent Document 2: Y. Tamaki et al., Nanoparticle Formation of Vanadyl Phthalocyanine by Laser Ablation of Its Crystalline Powder in a Poor Solvent, J. Phys. Chem. A 2002, 106, p.2135-2139 (2002)

Non-Patent Document 3: B 丄 i et al., "Enhancement of organic nanoparticle preparation by laser ablation in aqueous solution using surfactants, Applied Surface Science Vol. 210, p.171-176 (2003)

Disclosure of the invention Problems the invention is trying to solve

[0004] If the above-described micronization technology is used, there is a possibility that a new raw material and a preparation method can be provided, and application in a wide range of fields is expected. For example, in the field of materials, we develop new materials based on fine particles.In the field of drug discovery, ADME tests (absorption, distribution, metabolism, excretion tests) of drug candidates that are hardly soluble or insoluble due to micronization There is a possibility that it can be implemented.

[0005] However, in the method of performing atomization treatment by light crushing on a liquid to be treated in which a substance to be atomized and a solvent are mixed, it is necessary to determine whether or not actual atomization by laser light irradiation is performed. Is difficult. For this reason, there is a problem that it is not possible to easily determine whether or not the irradiation condition of the laser beam to the liquid to be treated is appropriately set.

[0006] For example, when the atomization treatment is performed by irradiating a laser beam under certain irradiation conditions, the presence or absence of the atomization actually occurring in the liquid to be treated at that time depends on the degree of coloring of the solvent accompanying the atomization. Alternatively, it is possible to make judgments based on the results of particle size measurement using electron microscope images (SEM). However, in any of these methods, it is impossible to determine the presence or absence of micronization only after the micronization treatment has been performed to some extent.

[0007] The present invention has been made to solve the above problems, and it is determined whether or not fine particles are formed by laser light irradiation, and the laser light irradiation conditions for the liquid to be treated are appropriately controlled. It is an object of the present invention to provide a method and a device for determining micronization conditions that can be controlled, and a method and an apparatus for producing fine particles using the same.

Means for solving the problem

[0008] The inventors of the present application have investigated a wide variety of substances with respect to the above-described laser light irradiation conditions and the presence or absence of fine particles due to laser light irradiation. As a result, they found that the optimum laser beam irradiation conditions differed greatly for each substance to be atomized. This indicates that it is necessary to optimize the irradiation conditions of the laser beam by some method when executing the processing for realizing the rapid atomization processing for each substance.

[0009] Further, based on the above findings, the inventor of the present application has studied a method for optimizing the irradiation condition of laser light. As a result, in the atomization treatment performed by irradiating the material particles of the substance with laser light, light emission occurs under the irradiation conditions that enable atomization. And arrived at the present invention.

[0010] That is, the method for determining micronization conditions according to the present invention includes the steps of (1) irradiating a treatment target liquid containing a substance to be micronized in a solvent with a laser beam of a predetermined wavelength to obtain a substance in the solvent. (2) measurement results of luminescence in the luminescence measurement step; and (2) a measurement result of the luminescence in the luminescence measurement step. And a condition determining step of determining irradiation conditions.

[0011] Further, the apparatus for determining micronization conditions according to the present invention includes: (a) a processing chamber for storing a processing target liquid containing a substance to be micronized in a solvent; and (b) a processing chamber stored in the processing chamber. Luminescence measuring means for measuring the luminescence accompanying the micronization generated when the treatment liquid is irradiated with laser light of a predetermined wavelength for micronizing a substance in the solvent; and (c) luminescence measurement by the luminescence measurement means. And a condition determining means for determining a laser light irradiation condition for the liquid to be treated based on the emission characteristics obtained from the measurement results.

[0012] According to the above-described method and apparatus for determining the atomization conditions, when the liquid to be treated containing the substance to be atomized is irradiated with laser light, the liquid to be treated is accompanied by the atomization. The resulting light emission is measured, and the laser light irradiation conditions are determined with reference to the light emission characteristics. As described above, by performing the emission measurement when performing the atomization processing, it is possible to determine during the execution of the processing the presence or absence of the atomization due to laser beam irradiation and the state of the atomization such as the processing speed. Then, by determining the irradiation conditions of the laser beam based on the emission characteristics that reflect the state of atomization of the liquid to be treated, the irradiation conditions are optimized such that the treatment speed is increased. It becomes possible to control the irradiation condition of the laser beam to the liquid quickly and reliably. In particular, in the method using luminescence measurement, it is possible to easily determine the state of micronization and determine the irradiation conditions of laser light.

[0013] A method for producing fine particles according to the present invention is a method for producing fine particles by subjecting a substance in a solvent of a liquid to be treated to light crushing, and includes the above-described method for determining fine particle formation conditions. By irradiating the liquid to be treated with laser light based on the irradiation conditions determined in the preparation step of preparing the liquid to be treated mixed with the solvent and the condition determining step, the solvent Laser irradiation step of atomizing the substance in Features.

Further, an apparatus for producing fine particles according to the present invention is an apparatus for producing fine particles by subjecting a substance in a solvent of a liquid to be treated to light crushing, wherein the apparatus for determining the above-mentioned fine particle-forming conditions includes: A laser light source for irradiating the treatment liquid with laser light for atomizing substances in the solvent, and a laser light irradiation condition for the laser light source based on the irradiation conditions determined by the condition determining means. And control means for controlling the

According to the above-described method and apparatus for producing fine particles, the irradiation conditions of laser light determined based on! / ヽ based on the emission characteristics are reflected by reflecting the state of fine particles in the liquid to be treated. And performing atomization processing. This makes it possible to suitably execute the atomization processing by laser light irradiation on the substance to be atomized contained in the liquid to be treated.

The invention's effect

According to the present invention, the emission measurement is performed when the atomization treatment is performed, and the irradiation condition of the laser beam is adjusted based on the emission characteristics reflecting the state of the atomization in the liquid to be treated. By making the determination, it becomes possible to control the irradiation condition of the laser beam to the liquid to be treated quickly and reliably.

Brief Description of Drawings

FIG. 1 is a configuration diagram schematically showing an embodiment of an apparatus for determining micronization conditions and an apparatus for producing microparticles using the apparatus.

FIG. 2 is a graph showing the relationship between emission intensity and laser light wavelength.

FIG. 3 is a graph showing the relationship between light emission intensity and laser light intensity.

FIG. 4 is a graph showing the relationship between emission intensity and laser light irradiation time.

FIG. 5 is a graph showing changes over time in laser light intensity and light emission intensity.

FIG. 6 is a graph showing wavelength dependence of emission intensity.

FIG. 7 is a graph showing time waveforms of laser light and light emission.

FIG. 8 is a graph showing a relationship between light emission intensity and laser light intensity.

FIG. 9 is a graph showing a particle size distribution of VOPc.

FIG. 10 is a graph showing the relationship between emission intensity and laser light irradiation time.

Explanation of reference numerals [0018] 1A: an apparatus for producing fine particles; 2, a liquid to be treated; 3, a processing chamber; 4, a solvent; 5, a raw material particle (substance); Measurement device, 12 ··· Irradiation light measurement device, 13 ··· Half mirror, 15 ··· Analysis device, 20 ··· Laser light source, 25 ··· Control device, 26 ··· Display device.

BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, preferred embodiments of a method for determining micronization conditions, a determination apparatus, a method for producing fine particles, and a production apparatus according to the present invention will be described in detail with reference to the drawings. In the description of the drawings, the same elements will be denoted by the same reference symbols, without redundant description. Also, the dimensional ratios in the drawings do not always match those in the description.

FIG. 1 is a configuration diagram schematically showing an embodiment of an apparatus for determining micronization conditions and an apparatus for producing microparticles using the apparatus according to the present invention. The fine particle producing apparatus 1A is an apparatus for producing fine particles by subjecting a substance in a solvent of a liquid to be treated to light crushing. The liquid to be treated 2 is composed of a solvent 4 such as water in a liquid phase, and raw material particles 5 of a substance to be micronized contained in the solvent 4.

[0021] The apparatus 1A for producing fine particles comprises: a determining apparatus 10 for determining fine-particle conditions for performing fine-particle processing by photo-crushing on raw material particles 5 of a substance in a solvent 4; And a control device 25 for controlling the atomization processing.

First, the configuration of the device 10 for determining the micronization conditions will be described. As shown in FIG. 1, the determination device 10 includes a processing chamber 3 for containing the liquid 2 to be processed. The processing chamber 3 is formed of, for example, a material such as quartz through which laser light for fine particle processing and light emission from the liquid to be processed 2 described later are transmitted. In addition, the processing chamber 3 and the liquid to be processed 2 are stirred, if necessary, with a magnet stick and a magnet stirrer for dispersing the raw material particles 5 in the solvent 4 by stirring the liquid to be processed 2 and the processing chamber 3 as required. A constant temperature device that maintains the temperature may be installed.

In the method for determining the micronization conditions by the present determination device 10, first, a liquid having a predetermined wavelength used for photo-crushing is applied to the liquid 2 to be treated containing the raw material particles 5 of the substance to be micronized in the solvent 4. By irradiating the light, the substance in the solvent 4 is finely divided. At the same time, The luminescence generated in the liquid to be treated 2 is measured. Then, based on the light emission characteristics obtained from the measurement result of the light emission, the irradiation conditions of the laser light to the liquid to be treated 2 are determined. As described above, such a method for determining the atomization conditions is based on the light emission phenomenon found by the inventors of the present invention and accompanying the atomization treatment by laser beam irradiation.

In the configuration shown in FIG. 1, the luminescence measuring device 11 is provided at a predetermined position with respect to the processing chamber 3 in which the liquid 2 to be irradiated with the laser beam is stored. The luminescence measuring device 11 measures the light from the processing chamber 3 and, in particular, measures the luminescence associated with the generation of fine particles generated when the liquid 2 to be treated is irradiated with laser light for crushing light. It is.

[0025] A half mirror 13 is disposed between the processing chamber 3 and the luminescence measuring device 11 as a light branching unit. At a position where light from the processing chamber 3 branched by the half mirror 13 is incident, an irradiation light measuring device 12 for monitoring light irradiated to the liquid 2 to be processed is installed. The irradiation light measuring device 12 detects the light component reflected and scattered by the liquid 2 or the processing chamber 3 in the laser light for crushing the light irradiating the liquid 2 to be treated, thereby performing the treatment. Monitor the laser beam irradiating liquid 2.

The measurement signal from the luminescence measuring device 11 and the measurement signal from the irradiation light measuring device 12 are input to the analyzer 15. The analyzer 15 is a condition determining means for determining the conditions for irradiating the liquid 2 to be treated with laser light based on the luminescence characteristics obtained from the luminescence measurement results of the luminescence measuring device 11.

Specifically, the analysis device 15 obtains information on the luminescence of two liquids to be treated, based on the measurement signal from the luminescence measurement device 11. In addition, the analyzer 15 obtains information on the laser beam irradiating the liquid 2 to be treated, based on the measurement signal of the irradiation light measuring device 12. Then, from the measurement results indicated by these pieces of information, the luminescence characteristics of the luminescence generated in the liquid to be treated 2 due to the atomization are obtained. The emission characteristics required here reflect the state of fine particles in the liquid 2 to be treated, such as the presence / absence of fine particles due to laser beam irradiation and the processing speed. The analyzer 15 determines the irradiation condition of the laser light to the liquid 2 to be treated by referring to the emission characteristics and taking into account processing conditions such as a desired processing speed.

Next, the configuration of a fine particle manufacturing apparatus 1A having the fine particle generation condition determining apparatus 10 having the above configuration will be described. The manufacturing apparatus 1 A includes, in addition to the determining apparatus 10, a high-power laser light source 20 that irradiates the liquid 2 to be treated contained in the processing chamber 3 with laser light for photocrushing having a predetermined wavelength. I have. The laser light source 20 supplies a laser beam having a wavelength suitable for atomizing the raw material particles 5 of the substance in the solvent 4 of the liquid 2 to be treated.

As the laser light source 20, a fixed-wavelength laser light source can be used when the wavelength to be set in the laser light is already a component. Alternatively, a tunable laser light source may be used as the laser light source 20. In this case, it is possible to appropriately set and irradiate laser light having an appropriate wavelength based on the light absorption characteristics of the substance. If necessary, the laser light source 20 may be provided with light intensity adjusting means such as an attenuation filter or an optical attenuator.

In particular, as shown in FIG. 1, in the configuration in which the determining device 10 determines the irradiation condition of the laser beam for light crushing, it is preferable to use a laser light source whose laser beam intensity can be easily adjusted. When it is necessary to adjust the wavelength of the laser beam, it is preferable to use a wavelength variable laser light source. Alternatively, a laser light source group including a plurality of fixed wavelength laser light sources having different laser light wavelengths may be used. Such a configuration is useful in that the determination device 10 can also determine the laser beam intensity dependence and laser beam wavelength dependence of micronization even when finding suitable laser beam irradiation conditions.

The laser light source 20 and the analyzing device 15 of the determining device 10 are connected to a powerful control device 25 such as a computer. The control device 25 controls the production of the fine particles by controlling the operation of each unit of the production device 1A including the above-described determination device 10. In particular, in the present embodiment, the control device 25 actually irradiates the liquid 2 to be processed by the laser light source 20 based on the suitable laser light irradiation conditions determined by the analyzer 15 which is the condition determining means. Laser beam irradiation conditions are controlled. With respect to specific laser light irradiation conditions controlled by the control device 25, conditions such as the power of the configuration of the laser light source 20, for example, the intensity of the irradiated laser light and the wavelength of the laser light, are controlled.

A display device 26 is connected to the control device 25. The control device 25 displays on the display device 26 a screen necessary for determining the atomization conditions by the determination device 10 or a screen related to the atomization process in the manufacturing apparatus 1A. Next, a method for determining the micronization conditions and a method for producing fine particles according to the present invention using the fine particle production apparatus 1A shown in FIG. 1 will be described.

First, water 4 as a solvent and raw material particles 5 of a substance to be atomized are mixed to prepare a liquid 2 to be treated, and the liquid 2 to be treated is introduced into the processing chamber 3 ( Preparation steps). At this time, the raw material particles 5 are contained in the solvent 4 in a state of a dissolved substance or a non-dissolved substance. Next, the laser light source 20 is controlled by the control device 25, and the laser light for light breaking having a predetermined wavelength is irradiated from the laser light source 20 onto the liquid 2 to be treated. By this laser light irradiation, the raw material particles 5 in the solvent 4 are turned into fine particles in the liquid 2 to be processed in the processing chamber 3 (laser light irradiation step).

On the other hand, the luminescence measurement device 11 measures the luminescence from the liquid 2 to be treated due to the generation of fine particles by laser beam irradiation (luminescence measurement step). Further, the irradiation light measuring device 12 monitors the laser light irradiated on the liquid 2 to be treated. The analysis device 15 obtains the light emission characteristics as a result of the light emission measurement by the light emission measurement device 11, and determines suitable irradiation conditions of the laser light based on the light emission characteristics (condition determination step). Then, the control device 25 controls the irradiation condition of the laser light to the liquid 2 to be treated by the laser light source 20, based on the irradiation condition determined by the analysis device 15. As a result, in the liquid 2 to be treated, the material particles 5 of the substance in the solvent 4 are subjected to the atomization treatment under desired conditions (laser beam irradiation step).

A description will be given of the method and apparatus for determining micronization conditions, the method for producing fine particles, and the effects of the apparatus according to the present embodiment.

According to the apparatus and method for determining micronization conditions shown in FIG. 1, when the processing target liquid 2 containing the raw material particles 5 of the substance to be micronized is irradiated with laser light, In the treatment liquid 2, the light emission caused by the generation of fine particles is measured, and the irradiation condition of the laser light is determined with reference to the light emission characteristics. As described above, by performing luminescence measurement using the luminescence measuring device 11 when performing the atomization process, it is possible to determine during the execution of the process the presence / absence of the atomization by the laser beam and the state of the atomization such as the processing speed. be able to.

The processing speed is increased by determining the laser beam irradiation conditions in the analysis device 15 based on the light emission characteristics reflecting the state of micronization in the liquid 2 to be processed. like For example, it is possible to control the irradiation condition of the laser light to the liquid 2 to be treated by the laser light source 20 quickly and surely, for example, by optimizing the irradiation condition. In particular, in the above-described method using the luminescence measurement by the luminescence measuring device 11, it is possible to easily and in real time determine the state of atomization and determine the irradiation condition of the laser beam.

[0040] Further, according to the fine particle production apparatus 1A and the production method using the apparatus 10 and the method for determining the micronization condition, the state of micronization in the liquid to be treated 2 is reflected. By performing the atomization process with reference to the laser light irradiation conditions determined based on the optical characteristics, the material particles 5 of the substance to be atomized contained in the liquid 2 to be treated are irradiated with the laser beam. It is possible to suitably execute the micronization process. The light emission phenomenon caused by the formation of fine particles will be specifically described later.

Here, as for the emission characteristics obtained by the analysis device 15 and used for determining the irradiation condition of the laser beam, specifically, it is preferable to obtain the characteristics of the emission intensity. Alternatively, it is preferable to obtain the characteristics of the light emission timing. Further, a time waveform of light emission according to a time change of the light emission intensity may be obtained. By referring to these emission characteristics, it is possible to suitably evaluate the state of fine particles in the liquid 2 to be treated.

[0042] In this case, it is preferable to select and use the luminescence measuring device 11 that can measure necessary luminescence parameters in accordance with the luminescence characteristics used for evaluating the state of micronization by the analyzer 15. . The luminescence parameters measured by the luminescence measuring device 11 include, for example, luminescence intensity, luminescence timing, time waveform due to luminescence time change, and the like.

In addition, in the case where the characteristic of the emission wavelength is obtained as the emission characteristic, it is preferable to use an emission measurement device 11 that can measure the emission wavelength. As such a configuration, there is a configuration in which a wavelength filter is provided to measure only the emission component in a specific wavelength band. Alternatively, a device capable of measuring an emission spectrum may be used as the emission measurement device 11. As a result, it is possible to evaluate various characteristics of light emission accompanying fine particle formation.

In the configuration in which the emission spectrum is measured by the emission measurement device 11, the analysis device 15 refers to the measured emission spectrum to separate the emission associated with the atomization from the emission of the particles themselves. Is possible. As a result, the luminous phenomenon associated with micronization can be selected. Alternatively, measurement can be performed to more accurately evaluate the state of micronization. For example, if the material of the raw material particles 5 to be micronized originally emits light, light emission occurs in advance with the micronization, and an emission spectrum is obtained in a state beforehand, and the emission spectrum is obtained using this emission spectrum. It is preferable to selectively separate the light emission accompanying the chemical conversion.

[0045] As a specific configuration of the luminescence measuring device 11 in such a case, for example, a photodetector used for measuring luminescence intensity, luminescence timing, and the like, and a multi-detector used for measuring a luminescence spectrum are provided. A configuration in which the spectrum analyzer used is combined can be used. Further, other configurations may be used.

Further, the irradiating light measuring device 12 for monitoring the laser light emitted from the laser light source 20 to the liquid 2 to be treated has a certain sensitivity to the wavelength of the emitted laser light. Therefore, it is preferable to use a photodetector capable of measuring a laser beam irradiation timing and a time waveform due to a time change of the laser beam.

[0047] The laser beam irradiation conditions determined by the analyzer 15 as the condition determining means include at least one of a laser beam irradiation time, a laser beam wavelength, a laser beam intensity, and a laser beam waveform. Is preferably determined. The irradiation conditions can be controlled by other parameters.

[0048] The material of the raw material particles 5 to be finely divided by laser light irradiation may be various substances. Such substances include organic compounds. Examples of the organic compound include an organic pigment, a condensed aromatic polycyclic compound, a drug (drug, drug-related substance), and the like. In the case of a drug, the photochemical reaction of the drug by the laser beam irradiation is sufficiently prevented by appropriately setting the irradiation conditions of the laser beam and efficiently forming the fine particles. Therefore, the fine particles can be produced without losing the medicinal effect of the drug. For the photochemical reaction, preferably select the wavelength of the laser beam applied to the liquid 2 to be treated (for example, select a wavelength in the infrared region that can avoid photodegradation due to the photochemical reaction, or a wavelength of 900 nm or more. ) Can further suppress the occurrence of photochemical reactions.

[0049] More specifically, an organic compound used as a drug often has a relatively weak chemical bond in its molecular structure. When such an organic compound is irradiated with light such as ultraviolet light, Although fine particles can be partially generated, at the same time, impurities may be generated due to a photochemical reaction of an organic compound in some parts via an electronically excited state. In particular, in the case of drugs (pharmaceuticals) to which organic compounds are administered into the body, such impurities must be avoided as much as possible because such impurities may cause side effects and adversely affect the living body. No. On the other hand, by producing fine particles of an organic compound by the above-described production method capable of efficiently performing the fine particle treatment and suppressing the occurrence of photochemical reaction, the generation of impurities can be sufficiently suppressed. Becomes possible.

[0050] In addition, as described above, by realizing micronization of a drug while maintaining its efficacy without losing its medicinal properties, it is possible to evaluate powerful physic studies, screening, etc. that cannot be evaluated in the form before micronization. It will enable the search and determination of compounds, ADME tests, general toxicity in animal preclinical studies, general pharmacology, pharmacology, biochemical studies, and clinical studies. Further, by the above-mentioned production method, it is possible to obtain an extremely wide variety of drugs that can be administered to living bodies. For this reason, the range of drug selection can be dramatically expanded. Further, since the surface area of the drug is increased by the microparticulation of the drug and the absorbability of the drug in living tissue is improved, effective drug fine particles can be obtained in a small amount. Such a micronization treatment is also effective for organic compounds other than drugs.

[0051] Specific examples of the organic compound to be micronized include, for example, a hardly soluble or insoluble drug such as a drug, clobetasone butyrate / carbamazepine. In addition, the above-described method and apparatus for determining micronization conditions and the method and apparatus for producing microparticles can be applied to drug candidate substances (natural products, compound libraries, etc.), quasi-drugs, cosmetics, etc., in addition to the above-mentioned drug substances. Is also applicable.

[0052] As a solvent for an organic compound such as a drug, a small amount of alcohols, sugars, and salts which preferably use water as described above may be contained. Alternatively, a solvent other than water may be used. Examples of such a solvent include ethyl alcohol which is a monohydric alcohol, glycols which are dihydric alcohols (such as propylene glycol and polyethylene glycol), and glycerol which is a trihydric alcohol. Vegetable oils such as soybean oil, corn oil, sesame oil and laccase oil can also be used as solvents. When these solvents are used as injections, they are preferably used as organic solvents for non-aqueous injections. it can.

[0053] The emission characteristics used for evaluating the state of atomization of the liquid to be treated 2 and the determination of the laser light irradiation conditions will be described more specifically. Note that the following description focuses on the measurement of the emission characteristics and the determination of the laser beam irradiation conditions, but generally such a measurement-determination operation is performed as a pre-stage of the atomization process. It may be performed, or may be performed together with the atomization treatment.

First, a method of using the relationship between the light emission intensity and the laser light wavelength as the light emission characteristics will be described.

FIG. 2 is a graph showing the relationship between emission intensity and laser light wavelength. In this case, the wavelength range of the laser beam to be measured is limited, and the laser beam intensity at which light emission accompanying fine particles is obtained is set in the wavelength range. Next, while the light intensity is fixed by the control device 25, only the laser light wavelength is changed, and the laser light is irradiated from the laser light source 20 to the liquid 2 to be treated. Then, the change in the luminescence intensity with respect to the wavelength is measured by the luminescence measurement device 11 and the analysis device 15, and the measurement result as illustrated in the graph of FIG. 2 is obtained as the luminescence characteristics. By referring to such emission characteristics, it is possible to suitably determine a laser light wavelength as a laser light irradiation condition for the liquid 2 to be treated.

Next, a method using the relationship between the light emission intensity and the laser light intensity as the light emission characteristics will be described.

FIG. 3 is a graph showing the relationship between the light emission intensity and the laser light intensity. In this case, set the wavelength of the laser beam to be measured. Next, while the wavelength is fixed by the control device 25, only the laser light intensity is changed, and the laser light is irradiated from the laser light source 20 to the liquid 2 to be treated. Then, a change in the light emission intensity with respect to the light intensity is measured by the light emission measurement device 11 and the analysis device 15, and the measurement result as illustrated in the graph of FIG. 3 is obtained as the light emission characteristics. By referring to such emission characteristics, it is possible to suitably determine the laser light intensity as a laser light irradiation condition for the liquid 2 to be treated.

Next, a method using the relationship between the light emission intensity and the laser light waveform as the light emission characteristics will be described.

In this case, the laser light wavelength and light intensity to be measured are set. Next, while the wavelength and the light intensity are fixed by the control device 25, only the pulse waveform of the pulse laser light is changed, and the laser light is irradiated from the laser light source 20 to the liquid 2 to be treated. Then, a change in the light emission intensity with respect to the light waveform is measured by the light emission measurement device 11 and the analysis device 15, and the measurement result is emitted. Obtained as optical characteristics. By referring to such emission characteristics, it is possible to suitably determine a laser light waveform as a laser light irradiation condition for the liquid 2 to be treated.

In such a case, specific conditions for the laser light waveform include, for example, waveform conditions such as rise time, fall time, and pulse width of the pulse light of the laser light. In addition, when measuring the light emission characteristics and controlling the irradiation conditions of the laser light with respect to such waveform conditions, it is necessary to use a laser light source having a variable laser light waveform as the laser light source 20. In each of the above-described methods, the emission measurement by the emission measurement device 11 needs to be performed a plurality of times by changing the wavelength, intensity, and pulse waveform of the laser light.

Next, a method using the relationship between the light emission intensity and the laser light irradiation time as the light emission characteristics will be described. FIG. 4 is a graph showing the relationship between the emission intensity and the laser light irradiation time. In this case, set the laser light wavelength and light intensity to be measured. Next, while the wavelength and the light intensity are fixed by the control device 25, the laser light is irradiated from the laser light source 20 to the liquid 2 to be treated. Then, the time change of the light emission intensity due to the laser light irradiation time is measured by the light emission measurement device 11 and the analysis device 15, and the measurement result as illustrated in the graph of FIG. 4 is obtained as the light emission characteristics.

[0059] According to the results of the study by the present inventors, as described above, under irradiation conditions that allow finer particles, light emission occurs with the finer particles due to light crushing. In addition, it was evident that the emission intensity decreased as the micronization process progressed, and no emission occurred in the sample that had been micronized to such an extent that the micronization hardly progressed. Therefore, by referring to the time change of the light emission intensity as shown in FIG. 4 as the light emission characteristic, the laser light irradiation time as the laser light irradiation condition for the liquid to be treated 2 is determined by the time T until the light emission stops. It can be suitably determined.

Here, as a specific method of determining the laser light irradiation time T, for example, a threshold is set for the light emission intensity, and the laser light irradiation time T is determined by the time until the light emission intensity changes to become equal to or less than the threshold. There is a method of determining the light irradiation time T. Alternatively, there is a method in which a threshold value is set for the change rate of the light emission intensity with time, and the laser light irradiation time T is determined based on the time until the change rate of the light emission intensity becomes equal to or less than the threshold value. Also, if other methods are used, good.

Next, a method of using light emission timing as light emission characteristics will be described.

As a method of determining the laser light irradiation condition with reference to the light emission timing, there is a method of referring to the light emission start timing with respect to the laser light irradiation timing as the light emission characteristic. This start timing corresponds to a delay time of light emission with respect to laser light irradiation. In this case, it is preferable to calculate the lower limit of the pulse width of the laser beam necessary for atomization of the obtained start timing force and determine the laser beam pulse width as the irradiation condition with reference to the lower limit.

As a light emission characteristic, there is a method of referring to a light emission end timing with respect to a laser light irradiation timing. This end timing corresponds to the duration of light emission with respect to laser beam irradiation. In this case, it is preferable to calculate the upper limit value of the pulse width of the laser beam necessary for atomization from the obtained end timing and determine the laser beam pulse width as the irradiation condition with reference to the upper limit value. Better ,.

A specific example of a method for determining the irradiation condition of the laser beam using the light emission timing will be described. FIG. 5 is a graph showing a time change of the laser light intensity and the light emission intensity. Here, the laser beam is irradiated with a pulse laser beam having a wide pulse width to perform atomization processing, and the timing of the emitted laser beam and light emission at this time is measured by the light emission measurement device 11, the irradiation light measurement device 12, and the analysis device 15. Measure and analyze.

In the example shown in FIG. 5, light emission starts at a start timing delayed by time t with respect to the laser light irradiation timing, and ends at the end timing of time t. This is

2

This indicates that fine particles are generated during the time t1 to the light irradiation. This

1 2

In the case of, the start timing t of emission is the lower limit and the end timing t is the upper limit,

1 2

It is preferable to set the pulse width W within the range of t <w≤t. This allows laser light illumination

1 2

It is possible to efficiently perform the atomization processing by the irradiation. Note that the pulse width of the laser beam may be set to a pulse width that is somewhat wider than the upper limit value t.

2

Next, the contents of the present invention will be described more specifically with specific data.

First, an emission spectrum and a time waveform of light emission when various substances are targeted for atomization will be described. Here, graphite, carbon Nanotubes, Si, VOPc (vanadyl phthalocyanine: pigment), clobetasone butyrate (pharmaceutical), carbamazepine (pharmaceutical), ibuprofen (pharmaceutical), and econazole nitrate (pharmaceutical) were selected as samples. Then, a suspension (liquid to be treated) of each sample was prepared at a concentration of lmgZml in water as a solvent 4, and 3 ml of the liquid to be treated 2 was placed in a quartz chamber cell (10 mm X 10 mm X 40 mm) as a processing chamber 3. Then, laser light irradiation for light crushing was performed.

As the laser light source 20, a YAG pulse laser was used. Light irradiation conditions are wavelength 1064ηm, repetition frequency 10Hz, FWHM 4.85ns, and energy per pulse is 300mJ Zpulse. Adjustment of the irradiation laser light intensity for causing a light emission phenomenon in each sample was performed by changing the spot diameter using a lens. In order to observe the light emission, a fast response type photodetector (DET210 manufactured by THORLABS: response speed Ins or less), a fast response type oscilloscope (Agilent infiniium: 2.25GHz, 8GSa / s), A channel type spectrometer (PMA11, manufactured by Hamamatsu Photonics KK) was used.

[0069] First, the emission spectrum of the above-described sample, which was generated with the formation of fine particles, was examined. FIGS. 6 (a)-(d) are graphs showing the wavelength dependence of the obtained emission intensity. In each graph, the horizontal axis indicates the emission wavelength (nm), and the vertical axis indicates the emission intensity (A.U.). Graph (1) in Fig. 6 (&) is ¥ 0, A2 is Si, graph (b) B1 is graphite, B2 is carbon nanotube, graph (c) is C1 carbamazepine, and graph (d) is D1 Clobetasone butyrate, D2 shows the emission spectrum of ibuprofen, and D3 shows the emission spectrum of econazole nitrate.

[0070] The irradiation laser light intensity at which the light emission phenomenon can be observed differs depending on the sample. For this reason, in this example, the VOPc and Si particles in Fig. 6 (a) have a light irradiation intensity of 450mjZcm ² 'pulse, the graphite of (b) and the carbon nanotube have a light irradiation intensity of 200miZcm ² ' pulse, and carbamazepine (c) in Fig. 6 (a). The clobetasone butyrate 'ibuprofen' and econazole nitrate in (d) were analyzed under the condition of 3000nj / cm ² · pulse.

As can be seen from these graphs in FIG. 6, emission spectra having almost the same tendency were obtained from all the samples. From this result, it is considered that the luminescence phenomenon was caused not by the physical properties of the sample but by the solvent (in this case, water). As to what caused such a light emission phenomenon, the surface of the raw material particles was exposed when the laser light was irradiated. It is conceivable that high-speed fine particles are emitted from the surface into the water, and light is emitted by the cavitation of the solvent. That is, light emission is observed when the fine particles are released from the raw material particles into the solvent solution at high speed, and the light emission characteristics are considered to be useful for monitoring the generation of fine particles. In this case, for example, when optimizing the laser light irradiation conditions necessary for the substance to be micronized, if the irradiation conditions that increase the emission intensity are determined, it is possible to obtain highly efficient fine particles. Conversion processing can be realized.

FIGS. 7 (a) to 7 (f) are graphs showing the temporal timing and time waveforms of laser light to be irradiated and light emission accompanying finer particles. In each graph, the dotted line indicates laser light, and the solid line indicates light emission accompanying finer particles. The horizontal axis indicates time (5 ns Zdiv), and the vertical axis indicates the detected signal intensity corresponding to the emission intensity. Fig. 7 (a) is a graphite, (b) is a carbon nanotube, (c) is VOPc, (d) is carbamazepine, (e) is ibuprofen, (f) is the time waveform of clobetasone butyrate. Each is shown.

According to these graphs in FIG. 7, in the graphite (a), the carbon nanotube in (b), and the VOPc in (c), light emission occurs without delay at the rise of the irradiation laser light. In other words, in these samples, it is assumed that under these irradiation conditions, the fine particles of the raw material particles are projected into the water almost synchronously with the irradiation. On the other hand, in the samples (d)-(f), which are pharmaceuticals, unlike the above samples, light emission occurs with a delay of about Ins with respect to the irradiation laser light. In other words, under these irradiation conditions, it is considered that a pulse width of at least Ins or more is required for the micronization of pharmaceuticals.

As described above, by comparing the timing between laser light and light emission, it is possible to obtain the lower limit laser light pulse width required for atomization. Conversely, in the case where the time width of light emission due to atomization with a longer laser light pulse width is shorter than that of laser light, the part of the pulse laser light without light emission contributes to atomization, It is presumed that. In this case, the upper limit of the pulse width required for atomization can also be obtained.

Next, the relationship between the light emission intensity and the laser light intensity will be described. Here, using VOPc as a sample, the relationship between the intensity of the irradiated laser beam and the intensity of the luminescence generated due to the atomization by the laser beam was obtained. Light irradiation conditions are wavelength of 1064 nm, repetition frequency of 10 Hz, FWHM of 4.85 ns, and energy per pulse is 300 mjZpulse. Also, The intensity of the emitted laser light was adjusted by varying the spot diameter using a lens. For the liquid to be treated, VOPc raw material particles were suspended in water at a concentration of lmgZml, and 3ml was placed in a quartz square cell to perform fine particle treatment.

FIG. 8 is a graph showing the relationship between the obtained light emission intensity and the laser light intensity. In this graph, the horizontal axis indicates the laser light intensity (mjZcm ² 'pulse), and the vertical axis indicates the light emission intensity (signal intensity corresponding to the maximum value of light emission, mV). In this case the VOPc, luminous phenomenon is observed from the irradiation laser beam intensity of about 30 0mjZcm ² 'pul _se, it tends to more emission intensity increases increase the light intensity was obtained. In other words, it can be seen that in the atomization of VOPc, by setting the irradiation conditions with a laser beam irradiation intensity of 300 mJZcm ² · pulse or more, the atomization treatment can be suitably performed.

[0077] It is to be noted that suitable irradiation conditions can be set for the laser light wavelength in the same manner according to the relationship between the emission intensity and the laser light wavelength. For example, in the relationship between the light emission intensity and the laser light wavelength, by determining the wavelength at which the light emission intensity becomes maximum, it is possible to determine the optimum laser light wavelength for the atomization treatment. In addition, by determining the wavelength range in which light emission can be obtained, a wavelength width that can be selected by fine particle formation can be obtained.

Next, the relationship between the light emission characteristics and the laser light irradiation time will be described. Here, using VOPc as a sample, the relationship between the laser light irradiation time and the emission intensity (the maximum value of the emission) was determined. The light irradiation conditions were a wavelength of 1064 nm, a repetition frequency of 10 Hz, a FWHM of 4.85 ns, a spot size of 3.5 mm φ, and an irradiation laser light intensity of 600 mjZcm ² 'pulse. The liquid to be treated was prepared by suspending VOPc raw material particles in water at a concentration of lmgZml, and placing 3 ml of the suspension in a quartz square cell to perform fine particle treatment.

[0079] In this experiment, a surfactant (Igapal CA-630: molecular weight 602) was added at a concentration of 0.29 mMolZl in order to prevent aggregation of the generated fine particles. The laser light irradiation time is before processing (0 minutes), 0.5 minutes, 3 minutes, 6 minutes, and 9 minutes. The emission intensity at each irradiation time and DMS (particle size distribution measurement device: Shimadzu SALD7000) The particle size distribution of the sample was also determined.

FIG. 9 is a graph showing the particle size distribution of VOPc in the liquid to be treated at each irradiation time. In this graph, the horizontal axis indicates the particle diameter (m), and the vertical axis indicates the relative particle amount. The According to this graph, the raw material particles of VOPc before treatment are distributed in the particle size range of about 15 to 70 m. On the other hand, if the processing time for atomization by laser beam irradiation is extended, it can be seen that after 6 minutes and 9 minutes, VOPc that is atomized near 200 nm in particle diameter, where the difference almost disappears, is obtained. You.

FIG. 10 is a graph showing the relationship between the light emission intensity and the laser light irradiation time. In this graph, the horizontal axis indicates the laser light irradiation time (minute), and the vertical axis indicates the emission intensity (mV). In this graph, the emission intensity is largest immediately after the irradiation of the laser beam, and gradually decreases as the atomization proceeds. After 6 minutes of irradiation, the luminescence intensity was reduced to about one-tenth of the initial value, and no luminescence could be observed after 9 minutes of irradiation.

This result corresponds to the state of micronization shown in the graph of FIG. In other words, it is estimated that after 9 minutes, the generation of high-speed fine particles that would cause cavitation in the solvent was eliminated. As described above, by monitoring the light emission phenomenon accompanying the atomization, it is possible to obtain information for determining the progress of the atomization and the completion state of the atomization. In addition, by determining the irradiation condition of the laser beam based on the information of the light emission characteristics, it is possible to suitably control the atomization treatment.

[0083] The method and apparatus for determining microparticulation conditions, the method for producing fine particles, and the apparatus for producing microparticles according to the present invention can be variously modified without being limited to the above-described embodiments and examples. For example, regarding the monitoring of laser light for light fracturing, referring to a signal from the laser light source 20 or a control signal sent from the control device 25 to the laser light source 20, the laser light intensity and the laser light irradiation timing are referred to. It is also possible to adopt a configuration for monitoring irradiation conditions such as. In this case, the irradiation light measuring device 12 shown in FIG. 1 is unnecessary.

[0084] The analysis device 15 and the control device 25 may be configured by separate computers, or may be configured by a single computer having both the analysis function and the control function. Further, the display device 26 used for displaying the light emission characteristics or the like may be omitted if unnecessary. Further, when the wavelength of the laser beam to be irradiated overlaps with the emission spectrum band, if it is necessary to give priority to the monitoring of the state of atomization, the laser beam wavelength may be set outside the emission spectrum band.

[0085] The method for determining micronization conditions according to the present invention generally includes (1) a method of determining a substance to be micronized. An emission measurement step of irradiating a liquid to be treated contained in the solvent with a laser beam of a predetermined wavelength to atomize the substance in the solvent and measuring the emission accompanying the atomization; (2) emission measurement It is preferable that the method further comprises a condition determining step of determining a laser light irradiation condition for the liquid to be treated based on the obtained light emission characteristics.

[0086] Further, the apparatus for determining micronization conditions according to the present invention generally includes (a) a processing chamber for accommodating a liquid to be processed containing a substance to be micronized in a solvent, and (b) a processing chamber. Luminescence measuring means for measuring luminescence associated with micronization generated when the liquid to be treated is irradiated with laser light of a predetermined wavelength for micronizing a substance in a solvent in the solvent, (c) It is preferable that the apparatus further includes condition determining means for determining the irradiation condition of the laser light to the liquid to be processed based on the emission characteristics obtained from the emission measurement result by the emission measurement means.

[0087] Further, in the method for determining the micronization condition, it is preferable to obtain a characteristic of the emission intensity as the emission characteristic in the condition determination step. Similarly, it is preferable that the determining device obtains a characteristic regarding the luminous intensity as the luminous characteristic.

In this case, as a specific method of determining irradiation conditions, in a condition determining step, a relationship between light emission intensity and laser light irradiation time is obtained as a light emission characteristic, and laser light irradiation as an irradiation condition is determined from the obtained relationship. A method for determining time can be used.

In the emission measurement step, the emission is measured a plurality of times while changing the wavelength of the laser light. In the condition determination step, the relationship between the emission intensity and the laser light wavelength is determined as the emission characteristic. It is possible to use a method of determining a laser beam wavelength as an irradiation condition.

In the emission measurement step, the emission is measured a plurality of times while changing the intensity of the laser light. In the condition determination step, the relationship between the emission intensity and the intensity of the laser light is determined as the emission characteristic. And a method of determining the laser light intensity as the irradiation condition.

[0091] Alternatively, in the emission measurement step, the emission is measured a plurality of times by changing the pulse waveform of the laser light, and in the condition determination step, the emission intensity and the emission intensity are obtained as the emission characteristics. It is also possible to use a method of determining the relationship with the light waveform and determining the laser light waveform as the irradiation condition. The laser light waveform in this case includes, for example, waveform conditions such as a rise time, a fall time, and a pulse width of the pulse waveform of the laser light.

[0092] Further, in the method for determining the micronization condition, it is preferable that in the condition determination step, a characteristic regarding emission timing is obtained as emission characteristics. Similarly, in the determination device, it is preferable that the condition determination means obtains all the characteristics of the light emission timing as the light emission characteristics.

[0093] As a specific method of determining irradiation conditions in this case, in the condition determining step, the emission start timing with respect to the laser light irradiation timing is obtained as the emission characteristic, and the obtained start timing force necessary for atomization is required. A method of calculating the lower limit of the pulse width of the laser light and determining the pulse width of the laser light as the irradiation condition with reference to the lower limit can be used.

In the condition determining step, the emission end timing with respect to the laser beam irradiation timing is determined as the emission characteristic, and the determined end timing force is determined by the pulse width of the laser light required for atomization. A method of calculating the upper limit and determining the laser light pulse width as the irradiation condition with reference to the upper limit can be used.

[0095] Generally, the laser light irradiation conditions determined based on the measured light emission characteristics include at least one of a laser light irradiation time, a laser light wavelength, a laser light intensity, and a laser light waveform. Is preferably determined. Alternatively, irradiation conditions other than these may be determined.

[0096] Further, in the method for determining the micronization conditions, the emission spectrum is measured in the emission measurement step, and in the condition determination step, the emission accompanying the micronization and the emission of the microparticles themselves are referred to with reference to the emission spectrum. It is preferable to separate light emission. Similarly, in the determination device, it is preferable that the emission measurement unit measures the emission spectrum, and the condition determination unit separates the emission accompanying the atomization from the emission of the particles themselves with reference to the emission vector. Good. According to such a configuration, it is possible to suitably determine the irradiation condition of the laser beam based on the emission characteristics.

[0097] In addition, the determination device performs the measurement for the laser beam irradiated to the liquid to be treated. It may be provided with an emission measuring means. This makes it possible to suitably determine the emission characteristics with reference to the measurement results of the laser beam and the emission.

[0098] The method for producing fine particles according to the present invention is generally a production method for producing fine particles by subjecting a substance in a solvent of a liquid to be treated to light crushing. And irradiating the liquid to be treated with laser light based on the irradiation conditions determined in the preparation step of preparing the liquid to be treated in which the substance and the solvent are mixed, and the condition determining step! It is preferable to include a laser light irradiation step of making the substance in the solvent into fine particles.

[0099] In addition, the apparatus for producing fine particles according to the present invention is generally an apparatus for producing fine particles by subjecting a substance in a solvent of a liquid to be treated to light crushing. A laser light source for irradiating the apparatus, a liquid to be treated with laser light for atomizing a substance in a solvent into fine particles, and a laser light from a laser light source based on the irradiation conditions determined by the condition determining means. And control means for controlling the irradiation conditions. Industrial applicability

The present invention provides a method and apparatus for determining fine particle conditions, which can determine the presence or absence of fine particles by laser light irradiation and can appropriately control the laser light irradiation conditions for the liquid to be treated. And a method and apparatus for producing fine particles using the same.

Claims

The scope of the claims

[1] A liquid to be treated containing a substance to be micronized in a solvent is irradiated with a laser beam of a predetermined wavelength to micronize the substance in the solvent and to measure light emission accompanying the micronization. A luminescence measurement step;

Based on the luminescence characteristics obtained from the luminescence measurement result in the luminescence measurement step

V, a condition determining step for determining an irradiation condition of the laser light to the liquid to be treated;

A method for determining micronization conditions, comprising:

[2] The determination method according to claim 1, wherein in the condition determining step, a characteristic of an emission intensity is obtained as the emission characteristic.

[3] In the condition determining step, a relationship between the light emission intensity and the laser light irradiation time is obtained as the light emission characteristic, and the obtained relationship power is determined as the laser light irradiation time as the irradiation condition. 3. The determination method according to claim 2, wherein:

[4] In the emission measurement step, while measuring the emission a plurality of times while changing the wavelength of the laser light,

In the condition determining step, a relationship between the light emission intensity and the laser light wavelength is obtained as the light emission characteristic, and the obtained relationship power is determined as the laser light wavelength as the irradiation condition. The determination method described in 2.

[5] In the emission measurement step, while measuring the emission a plurality of times while changing the intensity of the laser light,

In the condition determining step, a relationship between the light emission intensity and the laser light intensity is obtained as the light emission characteristic, and the obtained relational force is determined as the irradiation condition. Item 2.

[6] In the emission measurement step, while measuring the emission multiple times by changing the pulse waveform of the laser light,

In the condition determining step, a relationship between the light emission intensity and the laser light waveform is obtained as the light emission characteristic, and the obtained relational force determines a laser light waveform as the irradiation condition. The determination method described in 2.

7. The determination method according to claim 16, wherein in the condition determination step, a characteristic of a light emission timing is obtained as the light emission characteristic.

[8] In the condition determining step, a light emission start timing with respect to the laser light irradiation timing is obtained as the light emission characteristic, and the calculated start timing force calculates a lower limit value of the pulse width of the laser light required for atomization. 8. The method according to claim 7, wherein the laser light pulse width as the irradiation condition is determined with reference to the lower limit value.

[9] In the condition determining step, an emission end timing with respect to the irradiation timing of the laser light is obtained as the emission characteristic, and the obtained end timing force calculates an upper limit value of the pulse width of the laser light required for atomization. 8. The method according to claim 7, wherein the laser light pulse width as the irradiation condition is determined with reference to the upper limit value.

[10] In the emission measurement step, while measuring the emission spectrum,

10. The determination according to claim 11, wherein, in the condition determining step, the emission accompanying the micronization and the emission of the microparticles themselves are separated with reference to the emission spectrum. Method.

[11] A method for producing fine particles by subjecting a substance in a solvent of a liquid to be treated to light crushing, comprising the method for determining microparticulation conditions according to any one of claims 1 to 10, wherein the substance And a preparing step of preparing the liquid to be treated in which the solvent is mixed; and applying the laser beam to the liquid to be treated based on the irradiation conditions determined in the condition determining step. Irradiating a laser beam to irradiate the substance in the solvent to form fine particles.

A method for producing fine particles, comprising:

[12] a processing chamber containing a liquid to be processed containing a substance to be micronized in a solvent,

Luminescence measurement for measuring the luminescence accompanying the atomization that occurs when the liquid to be processed accommodated in the processing chamber is irradiated with laser light of a predetermined wavelength for atomizing the substance in the solvent. Means, Condition determination means for determining an irradiation condition of the laser light with respect to the liquid to be treated, based on a light emission characteristic obtained from the measurement result of the light emission by the light emission measurement means. apparatus.

13. The determining device according to claim 12, wherein the condition determining means obtains a characteristic regarding a light emission intensity as the light emission characteristic.

14. The determining device according to claim 12, wherein the condition determining means obtains a characteristic of an emission timing as the emission characteristic.

15. The method according to claim 12, wherein the condition determining means determines at least one of a laser light irradiation time, a laser light wavelength, a laser light intensity, and a laser light waveform as the irradiation condition. The determination device according to claim 1.

[16] The determination apparatus according to any one of [12] to [15], further comprising irradiation light measuring means for performing measurement on the laser light irradiated on the liquid to be treated.

[17] The emission measurement means measures the emission spectrum,

17. The determining apparatus according to claim 12, wherein the condition determining unit separates the emission accompanying the micronization and the emission of the microparticles themselves with reference to the emission spectrum.

[18] An apparatus for producing fine particles by photo-crushing a substance in a solvent of a liquid to be treated, the apparatus for determining fine-particle conditions according to any one of claims 12 to 17, and

A laser light source for irradiating the liquid to be treated with the laser light for atomizing the substance in the solvent;

Control means for controlling the irradiation condition of the laser light by the laser light source based on the irradiation condition determined by the condition determining means;

An apparatus for producing fine particles, comprising: