Drug introducing agent for administration into a living body and manufacturing method
First Claim
1. A method of manufacturing a carbonate apatite encapsulating a drug, the method comprising the step of incubating, without treating with ultrasound waves, a mixture comprising a calcium ion, a phosphate ion, a hydrogen carbonate ion, and a drug at an incubation temperature of 1°
- C. to 8°
C. and an incubation time of 1 minute or less to obtain a population of carbonate apatites encapsulating the drug, and wherein at least one of;
(i) 90% or more of the population of carbonate apatites have a particle size of 700 nm or less, and (ii) average particle size of the population of carbonate apatites is 50 nm or less.
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Abstract
The present invention provides carbonate apatites with a suitable particle size (average particle size and maximum particle size) as well as small variance (σ2) of particle sizes.
Provided is a method of manufacturing a carbonate apatite, the method comprising the step of incubating a mixture comprising a calcium ion, a phosphate ion, and a hydrocarbon ion, wherein an incubation temperature is 10° C. or lower and an incubation time of 10 minutes or less. Further, a carbonate apatite made by this method (e.g., carbonate apatite with a maximum particle size of 700 nm, average particle size of 30 nm and drug encapsulation rate of 98%, all in nanometer size) is provided.
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Citations
13 Claims
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1. A method of manufacturing a carbonate apatite encapsulating a drug, the method comprising the step of incubating, without treating with ultrasound waves, a mixture comprising a calcium ion, a phosphate ion, a hydrogen carbonate ion, and a drug at an incubation temperature of 1°
- C. to 8°
C. and an incubation time of 1 minute or less to obtain a population of carbonate apatites encapsulating the drug, and wherein at least one of;
(i) 90% or more of the population of carbonate apatites have a particle size of 700 nm or less, and (ii) average particle size of the population of carbonate apatites is 50 nm or less. - View Dependent Claims (2, 3, 4)
- C. to 8°
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5. A method of preparing an aqueous dispersion comprising a population of carbonate apatites which comprise a drug encapsulated therein, comprising the steps of:
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(a) incubating, without treating with ultrasound waves, a mixture comprising a calcium ion, a phosphate ion, a hydrogen carbonate ion, and a drug at an incubation temperature of 1°
C. to 8°
C. and an incubation time of 1 minute or less, to produce in the mixture a population of carbonate apatites encapsulating the drug;(b) subjecting the mixture after completion of incubation to high-speed centrifugation to produce a precipitate which comprises the population of carbonate apatites encapsulating the drug; and (c) dispersing the precipitate produced in step (b) in an aqueous solution to obtain the aqueous dispersion, and wherein at least one of;
(i) 90% or more of the population of carbonate apatites have a particle size of 700 nm or less, and (ii) average particle size of the population of carbonate apatites is 50 nm or less. - View Dependent Claims (6, 7, 8, 9)
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10. A method of manufacturing a carbonate apatite encapsulating a drug, comprising the steps of:
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(a) loading water, which is manufactured by an RO water manufacturing apparatus or by a distilled water manufacturing apparatus, into a container for stirring; (b) loading a phosphate ion and a hydrogen carbonate ion into the water of step (a) to produce a mixture; (c) adjusting pH of the mixture produced in step (b) to a pH value of 6.0 to 9.0, to obtain a pH-adjusted mixture; (d) loading a calcium ion and a drug into the pH-adjusted mixture obtained in step (c) and incubating the mixture at a temperature of 1°
C. to 8°
C. for 1 minute or less;(e) adding an emulsifying oily substance to the pH-adjusted mixture obtained in step (c) before or after said incubating in step (d); (f) centrifuging the pH-adjusted mixture to which the emulsifying oily substance has been added in step (e) in a centrifuge and discarding a supernatant to obtain a precipitate that comprises a population of carbonate apatites comprising the carbonate apatite-encapsulated drug; and (g) dispersing, without treating with ultrasound waves, the precipitate obtained in step (f) in a substance selected from air, distilled water, saline, and a thickener to obtain a dispersion comprising the population of carbonate apatites, and therefrom collecting the carbonate apatite-encapsulated drug, and wherein at least one of;
(i) 90% or more of the population of carbonate apatites have a particle size of 700 nm or less, and (ii) average particle size of the population of carbonate apatites is 50 nm or less. - View Dependent Claims (11, 12, 13)
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Specification