Method for producing medicine-containing particle and medicine-containing particle

Abstract

To provide a method for producing medicine-containing particles which is excellent in stability.SOLUTION: A method for producing medicine-containing particles includes: an emulsification step of emulsifying a functional medicine and converting it into an O / W type medicine emulsion; a second emulsification step of dripping the medicine emulsion into alkoxysilane, after the emulsification step; and an outer shell formation step of dropping the alkoxysilane into the medicine emulsion dropped into the alcohol, and coating an outer shell containing a siloxane bond as a main skeleton therewith. The produced medicine-containing particles are, for example, blended with a wood protective coating material. In wood where that is coated with wood protective coating material blended with the medicine-containing particles is coated and where a coating film is formed, after a while after coating, a functional medicine contained in the medicine-containing particles is eluted to the coating film, and the wood exhibits a function possessed by the functional medicine with time.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The technical field of the present specification relates to a method for producing drug-containing particles and drug-containing particles. [Background technology]

[0002] As a conventional drug-containing particle, Patent Document 1 describes a drug-containing particle using a liposome, and Patent Document 2 describes a drug-containing particle using an amphiphilic block polymer. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] JP 2008-133195 A [Patent Document 2] International Publication No. WO2018 / 055681 Summary of the Invention [Problem to be solved by the invention]

[0004] Conventional drug-containing particles have the problem that they may not be sufficiently stable.

[0005] The technology of the present specification has been made in consideration of the above points, and aims to provide a method for producing drug-containing particles with excellent stability. [Means for solving the problem]

[0006] The manufacturing method of drug-containing particles according to an embodiment of the present specification is characterized by having an emulsification step in which a functional drug is emulsified to form an O / W type drug emulsion, and an outer shell formation step in which the drug emulsion is coated with alkoxysilane to form an outer shell having a siloxane bond as the main skeleton.

[0007] According to the method for producing drug-containing particles of the embodiment, the drug emulsion is coated with an outer shell having a siloxane bond as the main skeleton, so that drug-containing particles with excellent stability can be produced.

[0008] The above-mentioned method for producing drug-encapsulated particles is characterized by comprising a second emulsification step, which is performed after the emulsification step and before the shell formation step, of dropping the drug emulsion into alcohol.

[0009] This makes it possible to preferably form an outer shell having a siloxane bond as the main skeleton in the drug emulsion.

[0010] Here, the drug-encapsulating particle according to the embodiment is characterized by having a drug emulsion and an outer shell having a siloxane bond as a main skeleton that encapsulates the drug emulsion.

[0011] According to the drug-containing particles of the embodiment, the functional drug is coated with an outer shell having a siloxane bond as the main skeleton, and therefore the particles can have excellent stability.

[0012] In the drug-containing particles, the drug emulsion may be emulsified with alcohol.

[0013] This allows the drug-containing particles to be easily coated with the drug emulsion to form an outer shell having a siloxane bond as the main skeleton.

[0014] The drug-containing particles may have an average particle size of 5 to 500 nm.

[0015] This allows the drug-containing particles to have excellent stability. Effect of the Invention

[0016] According to the method for producing drug-containing particles of the embodiment, drug-containing particles with excellent stability can be produced. [Brief description of the drawings]

[0017] [Figure 1] FIG. 2 is a flow chart showing a manufacturing process of the drug-containing particles according to the embodiment. [Diagram 2] FIG. 2 is a diagram showing a TEM (transmission electron microscope) photograph of a drug-containing particle of an embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0018] The method for producing the drug-containing particles according to the embodiment will be described below. The method for producing the drug-containing particles according to the embodiment includes an emulsification step of emulsifying a functional drug to form an O / W type drug emulsion, a second emulsification step performed after the emulsification step of dropping the drug emulsion into alcohol, and an outer shell formation step performed after the second emulsification step of dropping an alkoxysilane onto the drug emulsion dropped into the alcohol to coat the outer shell having a siloxane bond as the main skeleton.

[0019] The drug-containing particles manufactured by the method for manufacturing drug-containing particles according to the embodiment are, for example, mixed into a wood protective coating. When a wood substrate is coated with a wood protective coating containing the drug-containing particles and a coating film is formed, the functional drug contained in the drug-containing particles is dissolved into the coating film some time after coating, and the functional drug exerts its function over time.

[0020] In an embodiment, the functional agent may be, for example, a component having a function of suppressing deterioration of the coating film formed from the wood protective coating material, or a component that exerts a new function on the coating film. Examples of components having a function of suppressing deterioration of the coating film include preservatives, antifungal agents, anti-algae agents, and ultraviolet absorbers. Examples of components that exert a new function on the coating film include volatile oils such as aromatic oils, plasticizers, and the like. The functional agent may be a commercially available product according to these applications. The functional agent is mixed with a surfactant and purified water in the emulsification process to form an O / W type agent emulsion.

[0021] Surfactant is an emulsifier that covers the surface of functional drug particles and forms an emulsion that can be dispersed in water.In the embodiment, the surfactant can be used without any particular limitation as long as it is a surfactant that is usually used in paints such as wood protection paints, but in another embodiment, anionic surfactants and nonionic surfactants can be used, and in yet another embodiment, anionic surfactants can be used.

[0022] The anionic surfactant is a surfactant represented by the following general formula (1). (chemical 1) RO-(CH2CH2O) n -SO3M (1) (In the formula, R is an aromatic group or an aliphatic group having 8 to 16 carbon atoms, n is 0 to 10, and M is triethanolamine, ammonium, or sodium.) As the anionic surfactant represented by the general formula (1), for example, alkyl ether sulfates include triethanolamine alkyl ether sulfate, ammonium alkyl ether sulfate, and sodium alkyl ether sulfate; polyoxyethylene alkyl ether sulfates include triethanolamine polyoxyethylene alkyl ether sulfate, ammonium polyoxyethylene alkyl ether sulfate, and sodium polyoxyethylene alkyl ether sulfate; polyoxyethylene aryl ether sulfates include triethanolamine polyoxyethylene aryl ether sulfate, ammonium polyoxyethylene aryl ether sulfate, and sodium polyoxyethylene aryl ether sulfate. In another embodiment, polyoxyethylene aryl ether sulfates that have excellent emulsion stability of drug emulsions can be used. These anionic surfactants can be commercially available products.

[0023] The nonionic surfactant is a nonionic surfactant such as polyoxyethylene alkyl ether. For example, polyoxyethylene alkyl ether, polyoxyethylene lauric acid amide, polyoxyethylene nonylphenyl ether, polyoxyethylene dinonylphenyl ether, polyoxyethylene octylphenyl ether, polyoxyethylene dioctylphenyl ether, polyoxyethylene lauryl ether, polyoxyethylene stearyl ether, polyoxyethylene oleyl ether, polyoxyethylene cetyl ether, etc. can be used as the nonionic surfactant. Commercially available products can be used as the nonionic surfactant.

[0024] The functional drug is mixed with the surfactant and purified water in the emulsification step to form an O / W type drug emulsion. The surfactant can be blended in an amount of 1 to 20 parts by mass relative to 100 parts by mass of the functional drug. This is because a suitable particle diameter (5 to 500 nm) for the drug-containing particles can be obtained. When the blending amount of the surfactant relative to 100 parts by mass of the functional drug is less than 1 part by mass, the amount of the surfactant relative to the amount of the functional drug is small, and the drug emulsion may become large (1000 nm or more), and the stability of the drug emulsion or the drug-containing particles may be deteriorated. On the other hand, when the blending amount exceeds 20 parts by mass, although a suitable particle diameter is obtained, the amount of the surfactant relative to the amount of the functional drug is large, and the water resistance of the drug-containing particles may be poor, and ultimately the water resistance of the wood protective coating material containing the drug-containing particles may be poor. In another embodiment, the blending amount of the surfactant relative to 100 parts by mass of the functional drug can be 2 to 10 parts by mass, and in yet another embodiment, it can be 3 to 8 parts by mass.

[0025] The purified water can be blended in an amount of 10 to 200 parts by mass per 100 parts by mass of the functional drug. This is because it can be emulsified favorably. When the blending amount of purified water per 100 parts by mass of the functional drug is less than 10 parts by mass, the amount of water surrounding the drug emulsion is small, and the drug emulsion may aggregate. On the other hand, when it exceeds 200 parts by mass, the volatile content is high, and the handling may be poor. In another embodiment, the blending amount of purified water per 100 parts by mass of the functional drug can be 20 to 100 parts by mass, and in yet another embodiment, it can be 30 to 80 parts by mass.

[0026] The drug emulsion is dropped into alcohol, and then alkoxysilane is dropped into the drug emulsion dispersed in alcohol, thereby forming drug-containing silica particles.

[0027] The alcohol that the drug emulsion is dropped into can be ethanol and / or methanol, and the alcohol can be adjusted to be alkaline. The alkoxysilane that coats the drug emulsion is easily dissolved in an alcohol environment, and furthermore, the alkoxysilane can be made more soluble by adjusting the alcohol to be alkaline.

[0028] An alkoxysilane is a silane compound having an alkoxy group, which is hydrolyzed to produce silanol, which is condensed to produce a siloxane bond that covers the surface of the drug emulsion and becomes the outer shell of the drug-containing particle. In the drug-containing particle of the embodiment, the alkoxysilane can be used without any particular limitation, and examples thereof include tetramethoxysilane (Si(OCH3)4), methyltrimethoxysilane (SiCH3(OCH3)3), dimethyldimethoxysilane (Si(CH3)2(OCH3)2), trimethylmethoxysilane (Si(CH3)3OCH3), ethyltrimethoxysilane (SiC2H5(OCH3)3), diethyldimethoxysilane (Si(C2H5)2(OCH3)2), triethylmethoxysilane (Si(C2H5)3OCH3), propyltrimethoxysilane (SiC3H7 (OCH3)3), tetraethoxysilane (Si(OC2H5)4), methyltriethoxysilane (SiCH3(OC2H5)3), dimethyldiethoxysilane (Si(CH3)2(OC2H5)2), trimethylethoxysilane (Si(CH3)3OC2H5), ethyltriethoxysilane (SiC2H5(OC2H5)3), diethyldiethoxysilane (Si(C2H5)2(OC2H5)2), triethylethoxysilane (Si(C2H5)3OC2H5), propyltriethoxysilane (SiC3H7(OC2H5)3), or mixtures thereof.

[0029] Next, the method for producing the drug-containing particles is described. The method for producing the drug-containing particles includes an emulsification step of emulsifying a functional drug to obtain an O / W type drug emulsion, a second emulsification step performed after the emulsification step of dropping the drug emulsion into alcohol, and an outer shell forming step performed after the second emulsification step of dropping an alkoxysilane into the drug emulsion dropped into alcohol to cover the outer shell having a siloxane bond as the main skeleton.

[0030] The emulsification process is a process in which a functional drug, a surfactant, and purified water are put into a single container and stirred all at once with a dissolver mixer or the like to emulsify the functional drug into a drug emulsion. If the emulsification is insufficient, such as when the functional drug and purified water immediately separate after stirring, stirring is performed again until the functional drug is emulsified.

[0031] In the second emulsification step, the drug emulsion is dropped into ethanol that has been adjusted to be alkaline with ammonia water, and the surface of the drug emulsion is made compatible with the alkaline ethanol. The dropwise addition is carried out with stirring at room temperature (20 to 35°C) over 2 to 5 minutes, and stirring is continued for 20 to 40 minutes after the dropwise addition.

[0032] In the shell formation process, alkoxysilane is dropped onto the drug emulsion whose surface has an affinity for alkaline ethanol, and the drug emulsion is covered with a shell made of siloxane bonds. The drop is performed at room temperature (20 to 35°C) over 2 to 5 minutes while stirring, and stirring is continued for 18 to 30 hours after the drop. EXAMPLES

[0033] A flow diagram showing the manufacturing process of drug-containing particles is shown in Figure 1. Drug-containing particles were obtained through the following steps.

[0034] (emulsification process) ·Functional medicine 100mL Emulsifier (sodium polyoxyethylene aryl ether sulfate) 5mL ·Purified water 50mL These were placed in a container and stirred quickly with a dissolver mixer to emulsify the functional drug to form a drug emulsion.

[0035] (Second emulsification process) Ethanol 1500mL 40mL of 28% ammonia water The entire amount of the drug emulsion emulsified in the emulsification process was added dropwise to the alkaline ethanol composed of these components over a period of 3 minutes at room temperature (25 to 30°C) with stirring, and after addition, stirring was continued for 30 minutes to obtain a drug emulsion whose surface was compatible with the alkaline ethanol.

[0036] (Outer shell forming process) While stirring the drug emulsion, the surface of which is alkaline and compatible with ethanol, ·Alkoxysilane (tetraethoxysilane) 60mL After dropping, the mixture was stirred for 24 hours to coat the drug emulsion with a shell made of siloxane bonds.Then, the mixture was centrifuged (8000 rpm for 10 minutes) to remove water, and the mixture was dried (50°C for 24 hours) to obtain drug-encapsulated particles.

[0037] Example 1 In Example 1, aromatic oil (commercially available cypress oil) was used as a functional drug, and drug-containing particles containing cypress oil were obtained. A TEM (transmission electron microscope) photograph of the drug-containing particles obtained in Example 1 is shown in FIG. 2. The scale bar in FIG. 2 is 50 nm, and drug-containing particles with a particle diameter of 50 to 100 nm were obtained. The drug-containing particles obtained in Example 1 were blended into a wood protective paint, and this wood protective paint was applied to wood. After a while after painting, the wood coated with this wood protective paint had cypress oil as a functional drug encapsulated in the drug-containing particles dissolved into the coating film formed from the wood protective paint, and the wood was able to exude the scent of cypress oil.

[0038] Example 2 In Example 2, an ultraviolet absorber (triazine-based ultraviolet absorber) was used as a functional drug, and drug-containing particles containing the triazine-based ultraviolet absorber were obtained. In Example 2, drug-containing particles with a particle diameter of 50 to 200 nm were obtained. The drug-containing particles obtained in Example 2 were blended into a wood protective coating, and this wood protective coating was applied to wood. After a while after the wood protective coating was applied to the wood, the triazine-based ultraviolet absorber as a functional drug encapsulated in the drug-containing particles was dissolved into the coating film formed from the wood protective coating, and deterioration of the coating film was suppressed.

Claims

1. A method for producing drug-containing particles, comprising: an emulsification step of emulsifying a functional drug to form an O / W type drug emulsion; and an outer shell formation step of coating the drug emulsion with alkoxysilane to form an outer shell having a siloxane bond as its main skeleton.

2. The method for producing drug-containing particles according to claim 1, further comprising a second emulsification step of dropping the drug emulsion into alcohol after the emulsification step and before the shell formation step.

3. A drug-containing particle comprising a drug emulsion and an outer shell having a main skeleton of siloxane bonds and encapsulating the drug emulsion.

4. 4. The drug-containing particle according to claim 3, wherein the drug emulsion is emulsified with alcohol.

5. The drug-containing particle according to claim 3, characterized in that the average particle size is 5 to 500 nm.

Images