JP2005060330A - Globular protein powder and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a globular protein powder being such fine as to selectively deliver a drug to a target site by e.g., a powder inhalation method and being uniform in particle diameter and to provide a method for producing the same. <P>SOLUTION: While a protein solution is sprayed from a nozzle, the solution is comminuted into microparticles by the action of an air stream. Ultramicroparticles having particle diameters of 11 μm or smaller are separated and withdrawn from the microparticles. The ultramicroparticles are spray-dried in warm air or a dry atmosphere. Thus, an amorphous globular protein powder having a mean particle diameter of 11 μm or smaller and a standard deviation of particle diameters of 0.085 or smaller can be obtained. The globular protein powder is such fine as to selectively deliver a drug to the target site by e.g., a powder inhalation method and is uniform in particle diameter. Therefore, it can be selectively delivered to the target site by e.g. a powder inhalation method. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a globular protein powder and a production technique thereof.

  One factor that determines the pharmacokinetics of drugs is the particle size. By adjusting the particle diameter of the drug to be administered, the drug can reach a specific target site. For example, in the case of drug administration by the powder inhalation method, as shown in FIG. 13, by administering a drug powder with the particle diameter appropriately adjusted and matched to the target site, the throat, trachea, bronchus It is possible to selectively introduce a drug into the alveoli (see Patent Document 1).

  However, in the conventional method for producing a drug, since the powder or material to be used as the drug or drug carrier is finely powdered and dried, particle destruction, friction, overheating, etc. occur, so the drug powder is fine and has a uniform particle size. It was difficult to manufacture.

In particular, proteins are easily damaged and deteriorated by friction, overheating, etc., so that they are fine enough to selectively introduce a drug into a target site by a powder inhalation method, that is, an average particle diameter of 11 μm or less and a spherical shape with a uniform particle diameter. Producing protein powder has been very difficult with the prior art.
JP 2003-62074 A

  The problem to be solved by the present invention is to provide a spherical protein powder that is so fine that the drug can be selectively introduced into the target site by a powder inhalation method or the like and has a uniform particle size, and a method for producing the same.

  In order to solve the above problems, the spherical protein powder of the present invention is characterized in that the average particle size is 11 μm or less and the standard deviation of the particle size is 0.085 or less.

  This spherical protein powder is so fine that the drug can be selectively introduced into the target site by a powder inhalation method or the like and the particle size is uniform, so that the drug is selectively introduced into the target site by a powder inhalation method or the like. be able to.

  The globular protein powder of the present invention is preferably composed of an amorphous protein. When the globular protein powder is made of an amorphous protein, it is easier to adjust the easiness of dissolution of the globular protein powder in the body (difficult to dissolve) than when the globular protein powder is made of crystalline protein. By adjusting the ease of dissolution of the globular protein powder in the body, the expression timing and expression time of the physiological action can be controlled. Moreover, when this globular protein powder is applied to a drug carrier, it is possible to control the onset timing and the onset time of the drug effect.

  In addition, by selecting any one of albumin, α globulin, β globulin, and γ globulin as the protein, it is possible to give the spherical protein powder a function of expressing physiological action according to the selected substance.

  In addition, by administering a powder containing another protein preparation using a protein different from the powder raw material, insulin, or steroid to the spherical protein powder of the present invention by a powder inhalation method, the other protein Formulations, insulin, or steroids can be selectively introduced at the target site.

  In order to solve the above problems, a method for producing a spherical protein powder according to the present invention includes a fine particle generation step of generating a fine particle of a solution by crushing a protein solution from an nozzle while discharging the protein solution from a nozzle, and the fine particle generation step. A separation step of separating and taking out ultrafine particles having a particle diameter of 11 μm or less from the generated fine particles, and a drying step of spray-drying the ultrafine particles taken out in the separation step in warm air or a dry atmosphere; It is characterized by having.

  According to this method, it is possible to produce an amorphous spherical protein powder having an average particle size of 11 μm or less and a standard deviation of the particle size of 0.085 or less and having a uniform particle size. .

  In the production method of the present invention, it is preferable that the drying step includes a charge supply step for supplying a charge to the ultrafine particles. That is, when spraying and drying ultrafine particles in warm air or in a dry atmosphere, electric charges are supplied to the ultrafine particles to control the charged state of the ultrafine particles. Thereby, adhesion of ultrafine particles and adhesion to the inner wall of the apparatus used for production can be prevented, and spherical protein powder having a uniform particle diameter can be produced efficiently.

  In addition, if any one of albumin, α globulin, β globulin, and γ globulin is selected as the protein, a spherical protein powder having a uniform particle size composed of albumin, α globulin, β globulin, or γ globulin is efficiently used. Can be manufactured well.

  In addition, by making the protein solution contain other protein preparation, insulin, or steroid different from the protein in the solution, a spherical protein powder containing other protein preparation, insulin, or steroid can be produced. it can.

  The spherical protein powder of the present invention is so fine that the drug can be selectively introduced into the target site by a powder inhalation method or the like, and the particle size is uniform, so that it is selectively introduced into the target site by a powder inhalation method or the like. be able to.

  According to the production method of the present invention, an amorphous spherical protein powder having an average particle diameter of 11 μm or less and a standard deviation of particle diameter of 0.085 or less and having a uniform particle diameter is produced. be able to.

  Embodiments of the present invention will be described below with reference to the drawings.

  FIG. 1 is a configuration diagram of an ultrafine particle production apparatus for producing a globular protein powder by the production method of the present invention. The ultrafine particle production apparatus 1 includes an ultrafine particle generator 2 and a spray dryer 4.

  FIG. 2 is a diagram showing the configuration of the ultrafine particle generator 2 constituting the ultrafine particle production apparatus. As shown in this figure, the ultrafine particle generator 2 includes a cylindrical particle separation container 10 having a lower end closed and a lid 10a at the upper end. The lid 10 a of the fine particle sorting container 10 is provided with a two-fluid nozzle (fine particle generating nozzle) 12 that crushes and refines the protein aqueous solution with gas. Here, the two-fluid nozzle 12 ejects gas from the gas outlet to the outer periphery of the protein aqueous solution ejected from the liquid jet provided at the tip of the nozzle, and crushes and refines the protein aqueous solution with the gas. The fine particles of the aqueous solution are ejected.

  A rectifying cone (rectifying member) 14 for rectifying and guiding fine particles generated by the two-fluid nozzle 12 to the lower part of the fine particle sorting container 10 is provided in the fine particle sorting container 10. Here, the tip of the two-fluid nozzle 12 is disposed in the opening of the upper part of the rectifying cone 14. Further, a secondary gas supply pipe 18 extending from the secondary gas compressor 16 is disposed in the fine particle separation container 10, and the secondary gas from the secondary gas compressor 16 is opened at the lower portion of the rectifying cone 14. Supplied near the section. Further, in the fine particle sorting container 10, three fine particle sorting plates 20, 22, 24 are provided for suppressing the floating of the fine particles guided to the lower part of the fine particle sorting container 10 by the rectifying cone 14 and sorting the fine particles. ing.

  As shown in FIG. 3, the fine particle sorting plate 20 is a disk-shaped plate-like member having an opening 20a through which the rectifying cone 14 penetrates at the center, and a large number of fine particle passage holes 20b are provided. . Further, as shown in FIG. 4, the fine particle sorting plate 22 is a disk-shaped plate-like member having an opening 22a through which the rectifying cone 14 penetrates at the center, and a large number of fine particle passage holes 22b are provided. ing. The fine particle passage hole 22b is formed larger than the size of the fine particle passage hole 20b of the fine particle sorting plate 20. Further, as shown in FIG. 5, the fine particle sorting plate 24 is a disk-shaped plate-like member provided with an opening 24a through which the rectifying cone 14 penetrates in the center, and has a large number of fine particle passage holes 24b. Yes. The fine particle passage hole 24 b is formed larger than the size of the fine particle passage hole 22 b of the fine particle sorting plate 22.

  A liquid discharge port 10 b communicating with the liquid storage container 26 is provided at the bottom of the fine particle sorting container 10. The protein aqueous solution accumulated at the bottom of the fine particle sorting container 10 is discharged from the liquid discharge port 10 b and stored in the liquid storage container 26.

  The lid 10 a of the fine particle sorting container 10 is provided with a discharge unit 28 for discharging ultra fine particles separated from the fine particles in the fine particle sorting container 10. Here, the discharge part 28 is comprised by the guide part 28b connected to the attaching part 28a attached to the cover part 10a of the particulate sorting container 10, and the attaching part 28a. A power supply device 40 is connected to the guide tube 28b for supplying electric charges to the ultrafine particles discharged from the discharge unit 28.

  The power supply device 40 supplies a desired DC high voltage to the guide tube 28b of the discharge unit 28, and supplies and charges the ultrafine particles discharged from the discharge unit 28. By charging the ultrafine particles and controlling the charge amount in this way, it is possible to prevent the discharged ultrafine particles from adhering to the inner wall of the apparatus or the particles from adhering again.

  Further, a liquid supply pipe 30 for supplying the protein aqueous solution to the two-fluid nozzle 12 is provided between the liquid storage container 26 and the two-fluid nozzle 12. The liquid supply pipe 30 is provided with an electromagnetic valve 32 for adjusting the amount of liquid supplied to the two-fluid nozzle 12. The solution can be supplied to the two-fluid nozzle 12 from other than the liquid storage container 26 via the branch supply pipe 30a. A gas supply pipe 36 for supplying nozzle gas to the two-fluid nozzle 12 is provided between the nozzle supply compressor 34 and the two-fluid nozzle 12.

  The pressure of the secondary gas supplied into the fine particle separation container 10 by the above-described secondary gas compressor 16, the pressure of the nozzle gas supplied to the secondary fluid nozzle 12 by the nozzle supply compressor 34, and the solenoid valve 32. The amount of the protein aqueous solution supplied to the two-fluid nozzle 12 is controlled by the control device 42. Further, the control device 42 controls the amount of charge supplied to the guide tube 28b of the discharge unit 28 by the power supply device 40.

  Further, the control device 42 is connected to a particle size detection unit S1 for detecting the particle size distribution of the ultrafine particles discharged from the discharge unit 28 and a particle amount detection unit S2 for detecting the particle amount of the ultrafine particles. Detection values are input from the detection unit S1 and the particle amount detection unit S2. The particle size detection unit S1 and the particle amount detection unit S2 determine the distribution of the particle size of the ultrafine particles taken out from the ultrafine particle outlet (not shown) provided in the guide tube 28b and the amount of the ultrafine particles. To detect.

  Further, the control device 42 includes a particle diameter setting unit 44a for setting the particle diameter of the ultrafine particles discharged from the discharge unit 28, a particle amount setting unit 44b for setting the particle amount of the ultrafine particles, and a charge amount (supplied charge) of the ultrafine particles. A charge amount setting unit 44c for setting (amount) is connected.

  FIG. 6 is a diagram showing a configuration of the spray dryer 4 constituting the ultrafine particle manufacturing apparatus. As shown in this figure, the spray dryer 4 has a drying container 50, and the guide tube 28 b of the discharge part 28 of the ultrafine particle generator 2 is connected to the upper part of the drying container 50, so that the ultrafine particle Ultrafine particles generated by the generator 2 are supplied into the drying container 50. A blower 56 is connected to the upper portion of the drying container 50 via a heater 52 and a filter 54, and hot air is supplied into the drying container 50 by the operation of the blower 56.

  One end of a pipe 58 is connected to the discharge port 50 a of the drying container 50, and the other end of the pipe 58 is connected to the first cyclone 60. An exhaust port 60 a is provided at the lower end portion of the first cyclone 60, and the upper end portion is connected to the upper end portion of the second cyclone 64 through a pipe 62. An outlet 64 a is provided at the lower end of the second cyclone 64.

  Next, a method for producing a spherical protein particle using the ultrafine particle production apparatus 1 of this embodiment will be described by taking a method for producing a spherical albumin particle as an example.

  First, the particle size of the ultrafine particles discharged from the discharge unit 28 is set by the particle size setting unit 44a of the ultrafine particle generator 2, and the particle amount of the ultrafine particles discharged from the discharge unit 28 is set by the particle amount setting unit 44b. . Here, the set value of the particle diameter of the ultrafine particles is set to an arbitrary value of 11 μm (preferably 7 μm) or less according to the average particle diameter of the spherical albumin particles to be produced. Further, the charge amount setting unit 44c sets the charge amount of the ultrafine particles discharged from the discharge unit 28. Here, the charge amount is set such that ultrafine particles do not adhere to unnecessary portions such as the guide tube 28b of the discharge unit 28 and the inner wall of the spray drying device 4, and preferably the generated ultrafine particles do not recombine with each other. Set as appropriate. In order to prevent recombination of the ultrafine particles, it is preferable to make the ultrafine particles electrically neutral.

  After the setting of the particle size of the ultrafine particles, the setting of the particle amount of the ultrafine particles, and the setting of the charge amount of the ultrafine particles are completed, the ultrafine particles of the albumin aqueous solution are generated. That is, in the ultrafine particle generator 2, when air (nozzle gas) is supplied from the nozzle supply compressor 34 to the two-fluid nozzle 12 via the gas supply pipe 36, this air is supplied to the tip of the two-fluid nozzle 12. The aqueous solution of albumin in the liquid storage container 26 is sucked up by the jet output and supplied to the two-fluid nozzle 12 through the liquid supply pipe 30.

  In the two-fluid nozzle 12, the solution ejected from the liquid ejection port is crushed and refined by the air ejected from the gas ejection port, and the fine particles of the albumin aqueous solution are ejected. The fine particles of the albumin aqueous solution ejected from the two-fluid nozzle 12 are guided to the lower part of the fine particle sorting container 10 through the rectifying cone 14. On the other hand, air (secondary gas) from the secondary gas compressor 16 is supplied to the vicinity of the opening at the lower portion of the rectifying cone 14 via the secondary gas supply pipe 18.

  The fine particles of the albumin aqueous solution guided to the lower part of the fine particle sorting container 10 are controlled to rise by the fine particle sorting plates 20, 22, and 24 due to the upward flow of the air and the secondary gas ejected from the two-fluid nozzle 12. Through the fine particle passage holes 20b, 22b, and 24b provided in the sorting plates 20, 22, and 24, the inside of the fine particle separation container 10 is gradually lifted. That is, the fine particles having first passed through the fine particle sorting plate 24 are suppressed from floating by the fine particle sorting plate 22, and fine particles having a predetermined particle diameter are retained between the fine particle sorting plate 24 and the fine particle sorting plate 22. Here, fine particles having a large particle diameter fall to the bottom of the fine particle sorting container 10 by gravity.

  Further, the fine particles having passed through the fine particle sorting plate 22 are prevented from floating by the fine particle sorting plate 20, and fine particles having a predetermined particle diameter are retained between the fine particle sorting plate 22 and the fine particle sorting plate 20. Here, fine particles having a large particle diameter fall to the bottom of the fine particle sorting container 10 by gravity. The particle size of the fine particles staying between the fine particle sorting plate 22 and the fine particle sorting plate 20 is smaller than the particle size of the fine particles staying between the fine particle sorting plate 24 and the fine particle sorting plate 22.

  As the microparticles float in the fine particle sorting container 10 in this way, the fine particles having a large particle size fall to the bottom of the fine particle sorting container 10 and only the ultrafine particles having a uniform particle size with an average particle size of 7 μm or less are obtained. It is discharged from the discharge part 28 of the fine particle sorting container 10. Here, the ultrafine particles discharged from the discharge unit 28 have a charge corresponding to the charge amount set by the charge amount setting unit 44c. That is, the control device 42 outputs a control signal to the power supply device 40 based on the value set by the charge amount setting unit 44c, and the amount of charge supplied to the guide tube 28b of the discharge unit 28 by the power supply device 40. Take control. Note that the albumin aqueous solution accumulated at the bottom of the fine particle sorting container 10 is discharged from the liquid discharge port 10b, stored in the liquid storage container 26, and reused.

  The particle size distribution of the ultrafine particles discharged from the discharge unit 28 is detected by the particle size detection unit S1, and the particle amount of the ultrafine particles is detected by the particle amount detection unit S2. The detection values detected by the particle diameter detection unit S1 and the particle amount detection unit S2 are input to the control device 42. In the control device 42, the particle size of the ultrafine particles discharged from the discharge unit 28 is set to the value set by the particle size setting unit 44a, and the particle amount of the ultrafine particles is set by the particle amount setting unit 44b. The control signal is output to the secondary gas compressor 16, the solenoid valve 32, and the nozzle supply compressor 34 so as to obtain the value, and the air pressure supplied to the two-fluid nozzle 12 and the two-fluid nozzle 12 are supplied. The amount of the solution to be controlled is controlled, and the pressure of the secondary gas supplied into the fine particle separation container 10 is controlled.

  That is, the control device 42 controls the nozzle supply compressor 34 when the particle size of the ultrafine particles detected by the particle size detection unit S1 is larger than the size set by the particle size setting unit 44a. The pressure of the air supplied to the two-fluid nozzle 12 is increased. Further, the secondary gas compressor 16 is controlled to increase the pressure of the air supplied into the fine particle separation container 10. Thereby, the particle diameter of the ultrafine particles discharged from the discharge unit 28 is reduced.

  On the other hand, when the particle size of the ultrafine particles detected by the particle size detection unit S1 is smaller than the size set by the particle size setting unit 44a, the nozzle supply compressor 34 is controlled and supplied to the two-fluid nozzle 12. Reduce the air pressure. Further, the pressure of the air supplied into the fine particle separation container 10 is lowered by controlling the secondary gas compressor 16. Thereby, the particle diameter of the ultrafine particles discharged from the discharge unit 28 is increased.

  The particle size of the ultrafine particles discharged from the discharge unit 28 is controlled by controlling either the pressure of the air supplied to the two-fluid nozzle 12 or the pressure of the air supplied to the fine particle sorting container 10. Although it is possible to control both the pressure of the air supplied to the two-fluid nozzle 12 and the pressure of the air supplied to the fine particle separation container 10, the particle diameter of the ultrafine particles can be controlled more accurately. Can do.

  When the amount of fine particles detected by the particle amount detection unit S2 is smaller than the amount set by the particle amount setting unit 44b, a control signal is output to the electromagnetic valve 32 and supplied to the two-fluid nozzle 12. Increase the amount of solution being made. As a result, the amount of ultrafine particles discharged from the discharge unit 28 increases. On the other hand, when the amount of fine particles detected by the particle amount detection unit S2 is larger than the amount set by the particle amount setting unit 44b, a control signal is output to the electromagnetic valve 32 and supplied to the two-fluid nozzle 12. Reduce the amount of solution being made. As a result, the amount of ultrafine particles discharged from the discharge unit 28 is reduced.

  In this ultrafine particle generator 2, the particle diameter of the ultrafine particles detected by the particle diameter detection unit S1 is set by the particle diameter setting unit 44a to become the particle size, and the particle amount detected by the particle amount detection unit S2 is the particle amount. The above-described control is repeated until the amount of particles set by the setting unit 44b is reached. Thereafter, the ultrafine particles generated in the ultrafine particle generator 2 are supplied to the spray dryer 4.

  The ultrafine particles supplied into the drying container 50 of the spray dryer 4 are dried while being floated (flowed) by the hot air supplied into the drying container 50 through the heater 52 and the filter 54 by the operation of the blower 56, and then powdered. And gradually falls and is supplied to the first cyclone 60 from the outlet 50a. The ultrafine particles supplied to the first cyclone 60 are further supplied to the second cyclone 64, and the hot air is exhausted from the exhaust port 60 a of the first cyclone 60. The dried ultrafine particles are taken out from the outlet 64a of the second cyclone 64.

  As described above, in this manufacturing method, the albumin aqueous solution is crushed and refined by the airflow by ejecting the gas from the gas ejection port of the two-fluid nozzle 12 while ejecting the albumin aqueous solution from the liquid ejection port of the two-fluid nozzle 12. A fine particle generation step for generating fine particles of an albumin aqueous solution, and ultrafine particles having a particle diameter of 11 μm or less are separated from the fine particles generated in the fine particle generation step using the fine particle sorting plates 24, 22, 20 and the like. A separate separation step, a drying step for drying the ultrafine particles taken out in the separation step while being suspended in the drying container 50 of the spray dryer 4 by warm air, and an ultrafine particle in executing the drying step A spherical albumin powder by passing through a charge supplying step of supplying a charge to

  According to this production method, fine particles of an albumin aqueous solution are generated, and the fine particles are sorted by the fine particle size (mass) to generate an ultrafine particle group of an albumin solution having a uniform particle size of 11 μm or less in average particle size. Can do. Therefore, the spherical albumin powder consisting of ultrafine particles finally produced by drying can have an average particle size of 11 μm or less and a uniform particle size.

  In addition, when the albumin solution ultrafine particles were dried while being suspended by warm air, the superfine particles were supplied with electric charges to control the charged state of the ultrafine particles. Spherical albumin powder having a uniform particle diameter and shape can be efficiently produced by suppressing collision and adhesion of fine particles. That is, it is possible to produce spherical albumin powder with less dents and breakage by preventing damage to ultrafine particles during the drying process.

  Scanning electron micrographs of the spherical albumin powder produced by the method of the present invention are shown in FIG. 7, FIG. 8, and FIG. Further, scanning electron micrographs of spherical albumin powder produced by a conventional method using freeze-drying are shown in FIGS. 7 and 10 are 700 times, FIGS. 8 and 11 are 470 times, and FIG. 9 is 20000 times.

  The spherical albumin powder (spherical albumin powder of the present invention) shown in FIGS. 7, 8 and 9 has an average particle diameter of about 2 μm and a uniform particle diameter and shape. On the other hand, the spherical albumin powder (conventional spherical albumin powder) shown in FIG. 10 and FIG. 11 has an average particle diameter of about 20 μm, and the particle diameter and shape are not uniform.

  FIG. 12 shows the relationship (actual measurement result) between the particle diameter of spherical albumin powder and the number of particles present (relative particle amount). Table 1 below shows the median, mode, average value, and standard deviation of the particle diameter in each measurement result I, II, and III in FIG. The measurement results I and II show the results when the spherical albumin powder is produced by the production method of the present invention, and the measurement results III show the results when the particle sorting (sorting step) in the production method of the present invention is not performed.

  From this measurement result, it can be seen that according to the production method of the present invention, a uniform spherical albumin powder having a standard deviation of 0.085 or less can be produced. On the other hand, when the particle selection is not performed, the standard deviation is twice or more that in the production method of the present invention, and it can be seen that only spherical albumin powder having a non-uniform particle diameter can be produced.

  The spherical albumin powder produced by the production method of the present invention is so fine that the drug can be selectively introduced into the target site by a powder inhalation method or the like and has a uniform particle size. Can be selectively introduced.

  Further, when the crystal structure of the spherical albumin powder produced by the production method of the present invention was examined, it was found that it was composed of amorphous albumin. It is considered that the ultrafine particles of the aqueous albumin solution were rapidly dried while being suspended with warm air, so that the drying of the ultrafine particles was completed before crystallization, so that the particles became amorphous. When the spherical albumin powder is made of amorphous albumin, it is easier to adjust the easiness of dissolution of the spherical albumin powder in the body (difficult to dissolve) than when it is made of crystalline albumin. By adjusting the ease of dissolution of the spherical albumin powder in the body, the expression timing and expression time of the physiological action can be controlled. Moreover, when this spherical albumin powder is applied to a drug carrier, the onset timing and the onset time of the drug effect can be controlled.

  In the above embodiment, the method for producing a spherical albumin powder has been described. However, if one of α globulin, β globulin, and γ globulin is selected as the raw protein, α globulin, β globulin, or It is possible to efficiently produce a globular protein powder composed of γ globulin and having a uniform particle diameter.

  In addition, by adding other protein preparations using a protein different from the protein dissolved in the solution, insulin, or steroids to the protein solution before ultrafine particles, other protein preparations, insulin, or A spherical protein powder containing a steroid can be produced.

  Moreover, according to the manufacturing method of this invention, it is also possible to manufacture spherical protein powder with an average particle diameter of 1 micrometer or less. Therefore, it is also possible to produce spherical protein powders and drug carriers that can be applied as parenteral preparations and dispersible preparations for intravascular injection.

  Further, in the above embodiment, the spherical protein powder using water-soluble protein as a raw material and the production method thereof have been described. However, when the raw material protein is insoluble in water, other solvents (such as dilute neutral salts) ) To produce a spherical protein powder using water-insoluble protein as a raw material by making ultrafine particles of protein solution in which the raw material protein is dissolved in), selecting the particles, and drying while floating in warm air or a dry atmosphere. It is also possible to do.

  Further, the spherical protein powder produced as described above can be used in place of the conventional protein powder produced by using the freeze-drying method.

It is a block diagram which shows the structural example of the ultrafine particle manufacturing apparatus for manufacturing spherical protein powder with the manufacturing method of this invention.

It is a schematic block diagram which shows the structural example of the ultrafine particle generator in FIG.

It is a top view which shows the structural example of the fine particle selection plate in FIG.

It is a top view which shows the structural example of the fine particle selection plate in FIG.

It is a top view which shows the structural example of the fine particle selection plate in FIG.

It is a schematic block diagram which shows the structural example of the ultrafine particle generator in FIG.

It is a substitute figure of the scanning electron micrograph of the spherical albumin powder manufactured by the method of this invention.

It is a substitute figure of the scanning electron micrograph of the spherical albumin powder manufactured by the method of this invention.

It is a substitute figure of the scanning electron micrograph of the spherical albumin powder manufactured by the method of this invention.

It is a substitute figure of the scanning electron micrograph of the spherical albumin powder manufactured by the conventional method.

It is a substitute figure of the scanning electron micrograph of the spherical albumin powder manufactured by the conventional method.

It is a figure which shows the relationship (measurement result) of the particle diameter of spherical albumin powder, and the number of existence (relative particle amount).

It is explanatory drawing which shows the relationship between the average particle diameter of a chemical | medical agent and an arrival site | part in the case of chemical | medical agent administration by the powder inhalation method.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Ultrafine particle production apparatus 2 Ultrafine particle generator 4 Spray drying apparatus 10 Fine particle separation container 12 Two-fluid nozzle (fine particle generation nozzle)
20, 22, 24 Particle sorting plate 40 Power supply (charge supply source)
44a Particle size setting unit 44c Charge amount setting unit 50 Drying container 56 Blower S1 Particle size detection unit S2 Particle amount detection unit

Claims (6)

  A spherical protein powder having an average particle size of 11 μm or less and a standard deviation of the particle size of 0.085 or less.   2. The globular protein powder according to claim 1, comprising an amorphous protein.   The globular protein powder according to claim 2, wherein the protein is albumin, α globulin, β globulin, or γ globulin. A fine particle generation step of generating a fine particle of the solution by crushing with a gas stream while discharging the protein solution from the nozzle;
A separation step of separating and taking out ultrafine particles having a particle diameter of 11 μm or less from the fine particles generated in the fine particle generation step;
A drying step in which the ultrafine particles taken out in the fractionation step are spray-dried in warm air or a dry atmosphere.   The method for producing a spherical albumin powder according to claim 4, further comprising a charge supplying step for supplying a charge to the ultrafine particles when performing the drying step.   The method for producing a globular protein powder according to claim 4 or 5, wherein the protein is albumin, α globulin, β globulin, or γ globulin.