Method for producing spherical polylactic acid microparticles

Abstract

To provide a simple method for producing spherical polylactic acid fine particles having excellent heat resistance suitable for skin care applications such as cosmetics, facial cleansing agents, and body soaps.SOLUTION: Provided is a method for producing polylactic acid fine particles, comprising: a step of forming droplets by mixing a polylactic acid solution, prepared by dissolving polylactic acid having a D-body content of 10% or more in a solvent, and an aqueous solution of polyvinyl alcohol having a saponification degree of 68 to 85%, followed by stirring the mixture; a step of obtaining polylactic acid particles by removing the solvent from the droplets; and a step of adding a phosphate compound(s) to a solution containing polylactic acid particles and calcium ions under a basic condition.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a method for producing spherical polylactic acid microparticles from polylactic acid. [Background technology]

[0002] Organic microparticles synthesized from raw materials such as methyl methacrylate, styrene, nylon, and urethane, and having particle sizes on the nano- or micro-order, are being used for skin care purposes such as cosmetic additives and scrubbing agents in facial cleansers and body soaps, taking advantage of their extensibility and light-diffusing properties.

[0003] In skin care applications such as cosmetics, facial cleansers, and body soaps, it is expected that these will be washed away after use and released into the environment as wastewater, and therefore, in recent years, organic fine particles have been required to be biodegradable, meaning they can be broken down by microorganisms in the environment.

[0004] Known biodegradable resins include polylactic acid, polycaprolactone, polyhydroxyalkanoate, etc. However, these resins are usually handled in the form of pellets, and in order to exert the above-mentioned functions in skin care applications, they need to be processed into spherical microparticles. [Prior art documents] [Patent documents]

[0005] Patent Document 1 discloses a cosmetic containing biodegradable polyester particles with an average particle size of 3 to 50 μm. However, the specific particles disclosed are polyhydroxyalkanoate particles, and no consideration has been given to application to polylactic acid, a more general-purpose biodegradable resin. Patent Document 2 discloses a body cleanser composition containing a biodegradable plastic powder having an average particle size of 30 to 500 μm. However, since the powder is obtained by pulverization, it is not spherical, and there is room for improvement in terms of spreadability and tactile feel.

[0006] Patent Document 3 discloses a method for producing biodegradable polyester resin microparticles, but since it requires melt-kneading using a twin-screw extruder, special equipment is required and the process is complicated, leaving room for improvement.

[0007] Patent Document 4 discloses a simple method for producing spherical polylactic acid microparticles, but there is room for improvement in terms of heat resistance. [Patent Document 1] Japanese Patent Application Publication No. 5-194141 [Patent Document 2] Japanese Patent Application Publication No. 10-25239 [Patent Document 3] Japanese Patent Application Laid-Open No. 2002-363291 [Patent Document 4] Japanese Patent Application Laid-Open No. 2016-164240 Summary of the Invention [Problem to be solved by the invention]

[0008] An object of the present invention is to provide a simple method for producing spherical polylactic acid microparticles having excellent heat resistance and suitable for skin care applications such as cosmetics, face washes, and body soaps. [Means for solving the problem]

[0009] The present invention provides a method for producing polylactic acid microparticles, which comprises the steps of: forming droplets by mixing and stirring a polylactic acid solution in which polylactic acid having a D-isomer content of 10% or more is dissolved in a solvent with an aqueous polyvinyl alcohol solution having a saponification degree of 68 to 85%; removing the solvent from the droplets to obtain polylactic acid particles; and adding a phosphate compound to a solution containing polylactic acid particles and calcium ions under basic conditions. [Effects of the Invention]

[0010] The production method of the present invention makes it possible to easily obtain spherical polylactic acid microparticles with excellent heat resistance that are suitable for skin care applications such as cosmetics, facial cleansers, body soaps, etc. In particular, the method is advantageous in that it does not require special equipment, produces only a small amount of by-products, and is easy to handle. DETAILED DESCRIPTION OF THE INVENTION

[0011] The method for producing polylactic acid microparticles of the present invention includes a step of forming droplets by mixing and stirring a polylactic acid solution in which polylactic acid having a D-isomer content of 10% or more is dissolved in a solvent with an aqueous polyvinyl alcohol solution having a saponification degree of 68 to 85% (liquid formation step), and a step of adding a phosphate compound to a solution containing polylactic acid particles and calcium ions under basic conditions (coating step).

[0012] In the droplet formation process, a polylactic acid solution is used in which polylactic acid with a D-isomer content of 10% or more is dissolved in a solvent. Polylactic acid with a D-isomer content of less than 10% is not preferred due to its poor solubility in the solvent. Any solvent can be used as long as it can dissolve polylactic acid, but a solvent with high solubility is preferred because low solubility of polylactic acid reduces the yield. Furthermore, when removing the solvent and water in the removal process, the solvent must be removed preferentially over water, so a solvent with a lower boiling point than water is preferred. A lower boiling point than water allows it to be easily removed preferentially over water by reducing pressure. Ethyl acetate is a preferred solvent that meets these conditions.

[0013] The concentration of the polylactic acid solution is not particularly limited as long as it is a concentration that allows polylactic acid to dissolve. When the solvent is ethyl acetate, it is possible to prepare a solution up to about 20% by weight.

[0014] The aqueous polyvinyl alcohol solution is prepared using polyvinyl alcohol with a degree of saponification of 68 to 85%. Using only polyvinyl alcohol with a degree of saponification of more than 85% is not preferable because the particles become unstable and tend to aggregate during the removal process, but it is possible to use it in combination with polyvinyl alcohol with a degree of saponification of 68 to 85%. The concentration of the aqueous polyvinyl alcohol solution is preferably 1 to 20% by weight. By setting the concentration within this range, droplets are easily formed and the droplet diameter can be easily adjusted.

[0015] The polylactic acid solution and aqueous polyvinyl alcohol solution prepared as described above are mixed and stirred to form droplets. When the two are mixed at rest, they do not mix and separate into two layers. However, by applying shear force with a stirring blade or the like and stirring, droplets are formed in which the polylactic acid solution is emulsified and dispersed in the aqueous polyvinyl alcohol solution. The stronger the shear force and the longer the stirring time, the smaller the droplet diameter becomes. Therefore, by selecting the stirring means, adjusting the stirring rotation speed, and stirring time appropriately, droplets with the desired diameter can be formed.

[0016] The mixing ratio of the polylactic acid solution to the aqueous polyvinyl alcohol solution is preferably 100:10 to 100:40 by weight, which makes it easier to form droplets and also makes it easier to adjust the droplet diameter.

[0017] After forming the droplets in this way, the solvent is removed from the droplets to obtain polylactic acid particles, and then the coating process is carried out. The method for removing the solvent from the droplets is not particularly limited, but examples include vacuum concentration at a temperature corresponding to the boiling point of the solvent. For example, if the solvent is ethyl acetate, vacuum concentration is carried out at 45°C and 3 Torr for 3 hours. It is acceptable if some of the water is removed during this process. Note that if the viscosity of the droplets is high, it is difficult to remove the solvent, so water may be added to dilute the droplets as needed.

[0018] Next, by adding a phosphate compound to the polylactic acid particle dispersion and a solution containing calcium ions, the polylactic acid microparticles are converted into hydroxyapatite, which suppresses aggregation when extracted as a powder and improves heat resistance, making them easier to handle as microparticles.

[0019] As the calcium ion source, known water-soluble calcium compounds can be used, such as calcium nitrate, calcium nitrate tetrahydrate, calcium chloride, calcium chloride mono- to hexahydrate, calcium lactate, calcium chlorate dihydrate, calcium perchlorate, calcium bromide, calcium acetate, calcium glutamate, etc. These can be used alone or in combination of two or more. It is preferable to use 0.5 to 50 parts by weight of the calcium ion source compound per 100 parts by weight of polylactic acid.

[0020] As the phosphate compound, known water-soluble phosphate compounds can be used, such as diammonium hydrogen phosphate, ammonium dihydrogen phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate monohydrate, sodium dihydrogen phosphate dihydrate, potassium phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, etc. These can be used alone or in combination of two or more. It is preferable to use 0.5 to 50 parts by weight of the phosphate compound per 100 parts by weight of polylactic acid.

[0021] When adding a phosphate compound, it is preferable to make the solution basic, specifically, to maintain a pH of 7.8 or higher, preferably a pH of 8 or higher, and more preferably a pH of 9 or higher. By maintaining a pH of 9 or higher, the precipitation rate of hydroxyapatite becomes optimal, making it easier to form a hydroxyapatite coating layer. Examples of additives for making the solution basic include ammonia, sodium hydroxide, potassium hydroxide, etc. Among these, ammonia is preferred because it is easy to remove during drying. The amount of ammonia to be added is not particularly limited as long as it is within the range that satisfies the above basic condition.

[0022] During such a hydroxyapatite treatment, the temperature may be constant or may be changed during or at each stage, for example, from 0 to 95°C. The method for adding the phosphate compound is not particularly limited, and known methods can be used, such as charging the entire amount all at once at the beginning, charging a portion at the beginning and adding the remainder as a continuous feed, or adding intermittently. The time for adding the solution containing the phosphate compound is also not particularly limited and can be set as appropriate, for example, from 0.5 to 120 minutes from start to finish. The reaction time after adding the phosphate compound is also not particularly limited and can be set as appropriate depending on the progress of the reaction, for example, from 5 to 180 minutes.

[0023] Polylactic acid particles are obtained by removing water from an aqueous dispersion of hydroxyapatite-modified polylactic acid particles. Water removal is carried out by known methods such as filtration, centrifugal dehydration, and vacuum drying, and it is preferable to also perform washing to remove polyvinyl alcohol. Since the polylactic acid microparticles obtained in this manner may contain secondary aggregates or coarse particles, they may be purified, if necessary, by pulverization using a hammer mill or the like, sieving, or air classification.

[0024] The polylactic acid microparticles obtained in this way are roughly spherical with particle diameters of about 3 to 20 μm, and can therefore be used in a variety of applications where organic microparticles are used. In particular, they can be used in the same way as conventional organic microparticles in skin care applications such as cosmetics, facial cleansers, and body soaps, and they are biodegradable, so even if they are washed after use and released into the environment as wastewater, they pose a small environmental burden.

[0025] EXAMPLES The present invention will be described in more detail below with reference to examples and comparative examples, but these are given as specific examples and are not intended to limit the scope of the present invention. [Example]

[0026] Preparation of polylactic acid microparticle dispersion A polylactic acid solution was prepared by adding 120 parts by weight of pellet-like polylactic acid with a D-isomer content of 12% to 480 parts by weight of ethyl acetate and stirring. An aqueous polyvinyl alcohol solution was prepared by dispersing 4 parts by weight of polyvinyl alcohol (PVA 420H, product name, manufactured by Kuraray Co., Ltd.) with a saponification degree of 78 to 81.5% in 116 parts by weight of water and stirring at room temperature.

[0027] 600 parts by weight of the polylactic acid solution and 120 parts by weight of the polyvinyl alcohol aqueous solution were mixed and stirred with an anchor-shaped stirring blade to apply shear force, and it was confirmed that the mixture became cloudy and droplets were formed.

[0028] 540 parts of water was added to the resulting droplets to dilute the system, and the mixture was then concentrated under reduced pressure at 45° C. and 3 Torr for 3 hours to remove ethyl acetate, yielding an aqueous dispersion of polylactic acid microparticles. Example 1 720 parts by weight of the polylactic acid microparticle aqueous dispersion was placed in a separable flask equipped with a stirrer. Next, 58.2 parts by weight of a 28.6% calcium chloride monohydrate aqueous solution was added, followed by 10 parts by weight of 28% ammonia water to adjust the pH of the dispersion to 10.5. To this dispersion, 222 parts by weight of 4.0% ammonium dihydrogen phosphate was added 53.4 parts by weight of 28% ammonia water to adjust the pH to 11.2. 3.2% ammonium dihydrogen phosphate was added dropwise over 30 minutes, and the mixture was allowed to react at room temperature for 1 hour to obtain a dispersion of hydroxyapatite-coated polylactic acid microparticles. The resulting dispersion was centrifuged and vacuum dried to remove water, yielding hydroxyapatite-coated polylactic acid microparticles. The volume-average particle size of the resulting particles was measured using an electrical resistance particle size distribution analyzer (Beckman Coulter, Inc., Multisizer 3) and found to be 5.8 μm. Example 2 720 parts by weight of the polylactic acid microparticle aqueous dispersion was placed in a separable flask equipped with a stirrer. Next, 29.1 parts by weight of a 28.6% calcium chloride monohydrate aqueous solution was added, followed by 7.5 parts by weight of ammonia water to adjust the pH of the dispersion to 10.5. To this dispersion, 111 parts by weight of 4.0% ammonium dihydrogen phosphate was added to 26.7 parts by weight of 28% ammonia water to adjust the pH to 11.2. 3.2% ammonium dihydrogen phosphate was added dropwise over 30 minutes, and the mixture was allowed to react at room temperature for 1 hour to obtain a dispersion of hydroxyapatite-coated polylactic acid microparticles. The resulting dispersion was centrifuged and vacuum dried to remove water, yielding hydroxyapatite-coated polylactic acid microparticles. The volume-average particle diameter of the resulting particles was measured using an electrical resistance particle size distribution analyzer (Beckman Coulter, Inc., Multisizer 3) and found to be 6.2 μm. Example 3 720 parts by weight of the polylactic acid microparticle aqueous dispersion was placed in a separable flask equipped with a stirrer. Next, 17.5 parts by weight of a 28.6% calcium chloride monohydrate aqueous solution was added, followed by 5.0 parts by weight of 28% ammonia water to adjust the pH of the dispersion to 10.5. 3.2% by weight ammonium dihydrogen phosphate (3.2% by weight) was added dropwise to this dispersion over 30 minutes, with 67 parts by weight of 4.0% ammonium dihydrogen phosphate and 16 parts by weight of 28% ammonia water adjusted to pH 11.2. The mixture was then allowed to react at room temperature for 1 hour to obtain a dispersion of hydroxyapatite-coated polylactic acid microparticles. The resulting dispersion was centrifuged and vacuum dried to remove water, yielding hydroxyapatite-coated polylactic acid microparticles. The volume-average particle size of the resulting particles was measured using an electrical resistance particle size distribution analyzer (Beckman Coulter, Inc., Multisizer 3) and found to be 6.0 μm. Comparative Example 1 The aqueous dispersion of polylactic acid microparticles was subjected to a centrifugal dehydrator and a vacuum dryer to remove the water, yielding polylactic acid microparticles without a hydroxyapatite coating. The volume-average particle diameter of the resulting particles was measured using an electrical resistance particle size distribution analyzer (Beckman Coulter, Inc., Multisizer 3) and found to be 6.5 μm. Sieving evaluation The obtained stearic acid microparticles were passed through a vibrating sieve or an ultrasonic vibrating sieve with a mesh opening of 35 μm, and the numerical value was calculated from the mass of the microparticles that passed through the sieve. Evaluation was made as follows: 70% or more passed through; 20% or more but less than 70% passed through; and x passed through less than 20%. Comparative Example 1, which was evaluated as x, was not further evaluated. Tactile evaluation Ten panelists evaluated the texture. Industrially produced and used polymethyl methacrylate particles (Ganzpearl GMX-0610, product name, manufactured by Aica Kogyo Co., Ltd.) were used as a reference sample (Reference Example 1). The evaluation method involved taking 0.1 g of the powder, spreading it on the back of the hand, and rubbing it with the fingers. Sensory evaluations were compared for "smoothness," "whether or not there was a creaky feeling," and "feel" (comfort). A score of 0 was given if seven or more panelists rated it as good, a score of △ if four to six panelists rated it as good, and an × if three or fewer panelists rated it as good.

[0029] [Table 1]

[0030] As described above, in each example that met the required requirements of the present invention, approximately spherical polylactic acid microparticles with a particle diameter of several μm were obtained, but in each comparative example, problems occurred during the process and polylactic acid microparticles could not be obtained.

Claims

1. A method for producing polylactic acid microparticles, comprising the steps of: mixing and stirring a polylactic acid solution in which polylactic acid having a D-isomer content of 10% or more is dissolved in a solvent with an aqueous polyvinyl alcohol solution having a saponification degree of 68 to 85% to form droplets; removing the solvent from the droplets to obtain polylactic acid particles; and adding a phosphate compound to a solution containing polylactic acid particles and calcium ions under basic conditions.

2. 2. The method for producing polylactic acid microparticles according to claim 1, wherein the basic conditions are pH 9 or higher.

3. 3. The method for producing polylactic acid microparticles according to claim 1, wherein the amount of the phosphate compound added is 0.5 to 50 parts by weight per 100 parts by weight of polylactic acid.

4. 4. The method for producing polylactic acid microparticles according to claim 1, wherein the particle diameter of the obtained polylactic acid microparticles is 3 to 20 μm.

Images