Polyethylene glycol and method for producing the same

Abstract

This invention provides polyethylene glycol with excellent mixing uniformity and a method for producing the same. [Solution] A polyethylene glycol having a number average molecular weight of 2000 to 10000, wherein the particle size D50 at which the cumulative volume from the smallest particles accounts for 50% of the volume frequency particle size distribution measured by laser diffraction scattering using a dry powder disperser is 100 μm or more and 250 μm or less. Preferably, the polyethylene glycol has a particle size D10 at which the cumulative volume from the smallest particles accounts for 10% of the volume frequency particle size distribution measured by laser diffraction scattering is 30 μm or more and 130 μm or less.

Description

Technical Field

[0001] The present invention relates to polyethylene glycol and a method for producing the same.

Background Art

[0002] Conventionally, polyethylene glycol having a number average molecular weight of 2000 to 10000 has been known as a material for bath agents and pharmaceuticals. For example, Patent Documents 1 and 2 describe that polyethylene glycol can be used as an additive for bath agents.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0004] When polyethylene glycol is used as an additive, it is usually mixed with other components. However, when known polyethylene glycol is mixed with other components, a uniform mixture may not be obtained even after mixing for 30 minutes or more, and improvement is required.

[0005] The present invention has been made in view of the above problems, and an object thereof is to provide a polyethylene glycol having excellent mixing uniformity with other components and a method for producing the same.

Means for Solving the Problems

[0006] As a result of intensive studies to solve the above problems, the present inventors have arrived at the present invention. That is, the present invention is as follows. [1] A polyethylene glycol having a number average molecular weight of 2000 to 10000, wherein the particle size D50 at which the cumulative volume from the smallest particles accounts for 50% of the volume frequency particle size distribution, measured by laser diffraction scattering using a dry powder disperser, is 100 μm or more and 250 μm or less. [2] The polyethylene glycol according to [1], wherein the polyethylene glycol has a particle diameter D10 of 30 μm or more and 130 μm or less at which the cumulative volume from the small particle side in the volume frequency particle size distribution, measured by laser diffraction scattering using a dry powder disperser, is 10%. [3] The polyethylene glycol according to [1] or [2], wherein the polyethylene glycol has a particle diameter D90 of 200 μm or more and 440 μm or less in the volume frequency particle size distribution measured by laser diffraction scattering using a dry powder disperser, where the cumulative volume from the small particle side accounts for 90% of the distribution. [4] The polyethylene glycol according to any one of the following [1] to [3], wherein the CV value of the polyethylene glycol measured by laser diffraction scattering using a dry powder disperser is 80% or less. A method for producing polyethylene glycol according to any one of items [5][1] to [4], comprising the step of crushing polyethylene glycol having a number average molecular weight of 2000 to 10000 as a raw material. [Effects of the Invention]

[0007] According to the present invention, polyethylene glycol exhibiting excellent mixing uniformity with other components and a method for producing the same can be provided. [Modes for carrying out the invention]

[0008] [Polyethylene glycol] The polyethylene glycol of the present invention is a polyethylene glycol having a number average molecular weight of 2000 to 10000, and having a particle diameter D50 at which the cumulative volume from the smallest particle side accounts for 50% of the volume frequency particle size distribution, as measured by laser diffraction scattering using a dry powder disperser, is between 100 μm and 250 μm. The "particle diameter D50 at which the cumulative volume from the smallest particle side accounts for 50% of the volume frequency particle size distribution" is also called the "50% diameter (D50) in the volume-based cumulative particle size distribution."

[0009] The polyethylene glycol of the present invention has a number-average molecular weight (hereinafter also referred to as "Mn") of 2000 to 10000. Polyethylene glycol with Mn of 2000 to 10000 is in solid form. From the viewpoint of excellent handling properties, the Mn of polyethylene glycol is preferably 2500 or more, more preferably 2600 or more, preferably 9400 or less, and more preferably 9350 or less.

[0010] The manganese (Mn) of polyethylene glycol in the present invention can be measured by the method specified in "JIS K 1557" for calculating the hydroxyl value, or by the method specified in the "Average Molecular Weight Test" of the 18th edition of the Japanese Pharmacopoeia, "Macrogol 4000".

[0011] In this invention, the particle size D50 at which the cumulative volume from the smallest particles accounts for 50% of the volume frequency particle size distribution of polyethylene glycol (PEG), measured by laser diffraction scattering using a dry powder disperser, is determined from the volume-based cumulative particle size distribution curve of the PEG dispersion. In this invention, the laser diffraction scattering measurement is performed using a dry powder disperser. The cumulative particle size distribution curve can be obtained by measuring the particle size distribution of PEG dispersed by compressed gas (preferably compressed air) using a dry powder disperser, using a laser diffraction particle size distribution analyzer (for example, Malvern Panalytical's "Mastersizer 3000").

[0012] The D50 of the PEG in this invention is between 100 μm and 250 μm. This allows for excellent mixability, resulting in superior uniformity with other components. From the viewpoint of excellent mixing uniformity, D50 is preferably 120 μm or more, more preferably 130 μm or more, preferably 220 μm or less, and more preferably 200 μm or less.

[0013] In this invention, D10 of PEG is the particle size at which the cumulative volume from the smallest particle side in the volume frequency particle size distribution, as measured by laser diffraction scattering, accounts for 10%. D10, like D50, is determined from the volume-based cumulative particle size distribution curve of the PEG dispersion.

[0014] From the viewpoint of excellent mixing uniformity, the D10 of the PEG of the present invention is preferably 30 μm or more, more preferably 35 μm or more, preferably 130 μm or less, and more preferably 110 μm or less.

[0015] In this invention, D90 for PEG is the particle size at which the cumulative volume from the smallest particle side accounts for 90% of the volume frequency particle size distribution, as measured by laser diffraction scattering. D90, like D50, is determined from the volume-based cumulative particle size distribution curve of the PEG dispersion.

[0016] From the viewpoint of excellent mixing uniformity, the D90 of the PEG of the present invention is preferably 200 μm or more, more preferably 240 μm or more, preferably 440 μm or less, and more preferably 400 μm or less.

[0017] The coefficient of variation (CV) measured by the laser diffraction scattering method of the PEG of the present invention is preferably 80% or less, more preferably 60% or less. A larger CV value indicates a wider distribution, while a smaller CV value indicates a narrower distribution.

[0018] The CV value can be calculated by determining the standard deviation S1 in the volume-based cumulative particle size distribution and using the following formula. In the formula, "volume-average diameter" is the average particle diameter in the volume frequency particle size distribution measured by the PEG laser diffraction scattering method. CV value (%) = [(S1) / Volume-average diameter] × 100

[0019] [Method for producing polyethylene glycol] The PEG of the present invention is preferably produced by a production method including a step of crushing polyethylene glycol having a number average molecular weight Mn of 2000 to 10000 as a raw material.

[0020] The polyethylene glycol having Mn of 2000 to 10000 as a raw material (hereinafter also referred to as "raw material PEG") may be synthesized or a commercially available product may be used. Commercially available products include the PEG series manufactured by Sanyo Chemical Industries, Ltd. (having Mn of 2000 to 10000) [for example, "PEG2000 (Mn2000)", "PEG-4000S (Mn3400)", "PEG-4000N (Mn3100)", "PEG-6000P (Mn8300)", "PEG-6000S (Mn8300)", "PEG-10000 (Mn11000)", "PEG―20000 (Mn20000)", etc.], the Macrogol series manufactured by Sanyo Chemical Industries, Ltd. (having Mn of 2000 to 10000) [for example, "Macrogol 4000 (Mn3100)", "Macrogol 6000 (Mn8600)", etc.], "Polyethylene Glycol 4000" (Mn4000) manufactured by Sigma-Aldrich Co., LLC, etc.

[0021] Examples of the method for crushing the raw material PEG in the step of crushing the raw material PEG include a method of crushing using a crushing device such as a pin mill, a hammer mill, or a jet mill.

[0022] The production method of the PEG of the present invention may include a classification step. From the viewpoint of easily adjusting the particle size D50 to the range of 100 μm to 250 μm, the classification step is preferably performed after the step of crushing the raw material PEG. The classification step can be performed by using a sieve with a predetermined mesh size.

[0023] [Use] The PEG of the present invention has a predetermined particle size distribution and excellent uniformity in mixing with other components, making it suitable as an additive for bath additives, pharmaceuticals, etc. Other components can be selected according to the purpose of use. Examples of other components to be mixed with PEG include inorganic salts (sodium carbonate, calcium carbonate, sodium bicarbonate, sodium sesquicarbonate, sodium chloride, potassium chloride, sodium sulfate, magnesium sulfate, sodium metasilicate, etc.), organic acids (succinic acid, fumaric acid, malic acid, citric acid, maleic acid, tartaric acid, lactic acid) and their salts (alkali metal salts, alkaline earth metal salts), crude drugs (fennel, scutellaria baicalensis, phellodendron bark, chamomile, magnolia bark, rice fermentation extract, houttuynia cordata, calamus, chuanxiong, citrus peel, angelica root, spruce, chili pepper, ginseng, yuzu, mugwort, saposhnikovia root, mint leaf, ginger, licorice, cinnamon bark), enzymes, humectants, colorants, etc. These can be used individually or in combination of two or more types.

[0024] Regarding other components, from the viewpoint of mixing uniformity, it is preferable that the particle size distribution of the component differs from the particle size distribution of the PEG of the present invention in small amounts. Specifically, it is preferable that the difference between the particle size D50 of the other component and the particle size D50 of the PEG of the present invention is about -20 μm to 60 μm. It is preferable that the difference between the particle size D10 of the other component and the particle size D10 of the PEG of the present invention is about -20 μm to 70 μm. It is preferable that the difference between the particle size D90 of the other component and the particle size D90 of the PEG of the present invention is about -70 μm to 100 μm. When two or more compounds are used as other components, it is preferable that the difference between the particle size distribution of each compound and the particle size distribution of the PEG of the present invention is small. [Examples]

[0025] The present invention will be further described below with reference to examples and comparative examples, but the present invention is not limited thereto.

[0026] <Manufacturing Example 1> Polyethylene glycol [PEG-4000S, Mn3400, manufactured by Sanyo Chemical Industries, Ltd.] was used as the raw material PEG. This raw material PEG was crushed using a pin mill (crushing rotor rotation speed: 770 rpm), then passed through a sieve with a mesh size of 355 μm, and the sieved product with a mesh size of 63 μm was collected to obtain polyethylene glycol powder (A-1).

[0027] <Manufacturing Example 2> Polyethylene glycol [PEG-4000S, Mn3400, manufactured by Sanyo Chemical Industries, Ltd.] was used as the raw material PEG. This raw material PEG was crushed using a pin mill (crushing rotor rotation speed: 900 rpm), then passed through a sieve with a mesh size of 355 μm, and the sieved product with a mesh size of 90 μm was collected to obtain polyethylene glycol powder (A-2).

[0028] <Manufacturing Example 3> Polyethylene glycol [PEG-4000S, Mn3400, manufactured by Sanyo Chemical Industries, Ltd.] was used as the raw material PEG. This raw material PEG was crushed using a pin mill (crushing rotor rotation speed: 900 rpm), then passed through a sieve with a mesh size of 355 μm, and the sieved product with a mesh size of 63 μm was collected to obtain polyethylene glycol powder (A-3).

[0029] <Manufacturing Example 4> As the raw material PEG, polyethylene glycol ["Polyethylene Glycol 4000", Mn4000, manufactured by Sigma-Aldrich LLC] was classified using sieves with mesh sizes of 355 μm, 212 μm, and 180 μm. Particles between the 355 μm and 212 μm sieves, particles between the 212 μm and 180 μm sieves, and the material that passed through the 180 μm sieve were recovered. Polyethylene glycol powder (A-4) was obtained by mixing the particles between the 355 μm and 212 μm sieves at a ratio of 15% by weight, the particles between the 212 μm and 180 μm sieves at a ratio of 10% by weight, and the material that passed through the 180 μm sieve at a ratio of 75% by weight.

[0030] <Manufacturing Example 5> As the raw material PEG, polyethylene glycol [manufactured by Sanyo Chemical Industries, Ltd., "Macrogol 4000" Mn3100] was classified with a sieve having an aperture of 355 μm, and the passed product was collected to obtain polyethylene glycol powder (A-7).

[0031] <PEGs used in Examples and Comparative Examples> (A-1): Polyethylene glycol powder manufactured in Production Example 1 (A-2): Polyethylene glycol powder manufactured in Production Example 2 (A-3): Polyethylene glycol powder manufactured in Production Example 3 (A-4): Polyethylene glycol powder manufactured in Production Example 4 (A-5): "Macrogol 6000" (polyethylene glycol powder with Mn8600) manufactured by Sanyo Chemical Industries, Ltd. (A-6): "Macrogol 4000" (polyethylene glycol powder with Mn3100) manufactured by Sanyo Chemical Industries, Ltd. (A-7): Polyethylene glycol powder manufactured in Production Example 5

[0032] <Measurement of particle size distribution of PEG> (A-1) to (A-7) of the PEG particle size distribution was measured by laser diffraction method using a laser diffraction particle size distribution measuring device (manufactured by Malvern Panalytical, "Mastersizer 3000"). The compressed air pressure in the dry powder disperser during measurement was set to 0 bar. The particle size distribution of (A-1) to (A-7) of the PEG is shown in Table 1.

[0033]

Table 1

[0034] <Evaluation test: Mixing uniformity> The mixing uniformity of PEG and other components was evaluated by the following method. The PEG in (A-1) was the PEG from Examples 1-1 and 1-2, the PEG in (A-2) was the PEG from Examples 2-1 and 2-2, the PEG in (A-3) was the PEG from Examples 3-1 and 3-2, the PEG in (A-4) was the PEG from Examples 4-1 and 4-2, and the PEG in (A-5) was the PEG from Examples 5-1 and 5-2. The PEG in (A-6) was replaced with the PEG in Comparative Examples 1-1 and 1-2, and the PEG in (A-7) was replaced with the PEG in Comparative Examples 2-1 and 2-2. Two other ingredients commonly used in bath additives were used: [Ingredient (a): Sodium bicarbonate and magnesium sulfate; Ingredient (b): Sodium chloride, sodium bicarbonate, and potassium chloride]. For the other ingredients, the particle size distribution was measured using the same method as for PEG. The measurement results for the particle size distribution of the other ingredients [Ingredient (a) and Ingredient (b)] are shown in Table 2.

[0035] (1) Evaluation of mixing uniformity after 2 minutes of mixing (1-1-1) Sample preparation [using component (a) as another component] 2.5g (10.0 wt%) of sodium bicarbonate [Tosoh Corporation's "Sodium Bicarbonate"], 2.5g (10.0 wt%) of magnesium sulfate [Fujifilm Wako Pure Chemical Industries, Ltd.'s "Anhydrous Magnesium Sulfate"], and 20g (80.0 wt%) of polyethylene glycol powder listed in Table 1 were placed in a small mayonnaise bottle and mixed for 2 minutes to obtain a mixed powder. A "Pot Blender Mini PBS-MINI-SF" manufactured by Makino Sangyo Co., Ltd. was used as the mixer. The mixed powder was divided into three parts after mixing: the top, middle, and bottom. The total weight of the mixed powder was divided into three equal parts. Ultrapure water was added to each of the three divided parts of the mixed powder to a concentration of 10% by weight, and samples were prepared.

[0036] (1-1-2) Sample preparation [using component (b) as another component] 0.54 g (2.6 wt%) of sodium chloride [Sodium Chloride manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.], 0.27 g (1.3 wt%) of sodium bicarbonate [Sodium Bicarbonate manufactured by Tosoh Corporation], 0.08 g (0.4 wt%) of potassium chloride [Potassium Chloride manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.], and 20.11 g (95.7 wt%) of polyethylene glycol powder listed in Table 1 were placed in a small mayonnaise bottle and mixed for 2 minutes to obtain a mixed powder. A "Pot Blender Mini PBS-MINI-SF" manufactured by Makino Sangyo Co., Ltd. was used as the mixer. The mixed powder was divided into three parts after mixing: the top, middle, and bottom. The total weight of the mixed powder was divided into three equal parts. Ultrapure water was added to each of the three divided parts of the mixed powder to a concentration of 10% by weight, and samples were prepared.

[0037] (1-2-1) Quantitative determination and evaluation of elements in the sample [using component (a) as another component] For each sample obtained in (1-1-1), the elements (Na, Mg) in the sample were quantified by X-ray fluorescence analysis (XRF), and their content (weight %) was calculated and evaluated according to the following criteria. The results are shown in Table 3. A Rigaku Corporation "Supermini 200" X-ray fluorescence analyzer was used as the XRF measurement device. The elemental content (by weight %) was calculated using the following formula. Elemental content (weight %) = (measured value × dilution ratio) ÷ theoretical content × 100 (Evaluation criteria) The closer the element content is to 100%, the higher the uniformity. ○ (High mixing uniformity): In the upper, middle, and lower parts, the content of each element (Na, Mg) is between 90% and 120% by weight. △(Uniform mixing): At least one element is present in 80% by weight or more and less than 90% by weight and / or more than 120% by weight and 130% by weight or less in at least one of the upper, middle, and lower sections, but does not include samples with an element content of less than 80% by weight or more than 130% by weight. × (Poor mixing uniformity): In at least one of the upper, middle, and lower sections, the content of at least one element is less than 80% by weight and / or greater than 130% by weight.

[0038] (1-2-2) Quantitative determination and evaluation of elements in the sample [using component (b) as another component] For each sample obtained in (1-1-2), the elements (Na, Cl, K) in the sample were quantified by X-ray fluorescence analysis (XRF), and their content (weight %) was calculated and evaluated according to the following criteria. The results are shown in Table 4. A Rigaku Corporation "Supermini 200" X-ray fluorescence analyzer was used as the XRF measurement device. The elemental content (by weight %) was calculated using the following formula. Elemental content (weight %) = (measured value × dilution ratio) ÷ theoretical content × 100 (Evaluation criteria) The closer the element content is to 100%, the higher the uniformity. ○ (High mixing uniformity): In the upper, middle, and lower parts, the content of each element (Na, Cl, K) is between 90% and 120% by weight. △(Uniform mixing): At least one element is present in 80% by weight or more and less than 90% by weight and / or more than 120% by weight and 130% by weight or less in at least one of the upper, middle, and lower sections, but does not include samples with an element content of less than 80% by weight or more than 130% by weight. × (Poor mixing uniformity): In at least one of the upper, middle, and lower sections, the content of at least one element is less than 80% by weight and / or greater than 130% by weight.

[0039] (2) Evaluation of mixing uniformity after 10 minutes of mixing (2-1-1) Sample preparation [using component (a) as another component] The analytical sample was prepared in the same manner as in (1-1-1), except that it was mixed for 10 minutes. The 10 minutes of mixing was performed by changing the direction of rotation every 2 minutes. (2-1-2) Sample preparation [using component (b) as another component] The analytical sample was prepared in the same manner as in (1-1-2), except that it was mixed for 10 minutes. The 10 minutes of mixing was performed by changing the direction of rotation every 2 minutes. (2-2-1) Quantitative determination and evaluation of elements in the sample [using component (a) as another component] In (1-2-1), the elements (Na, Mg) in the sample were quantified and their content (weight %) was calculated and evaluated in the same manner as in (1-2-1), except that the sample obtained in (2-1-1) was used. The results are shown in Table 3. (2-2-2) Quantitative determination and evaluation of elements in the sample [using component (b) as another component] In (1-2-2), the elements (Na, Cl, K) in the sample were quantified and their content (weight %) was calculated and evaluated in the same manner as in (1-2-2), except that the sample obtained in (2-1-2) was used. The results are shown in Table 4.

[0040] (3) Evaluation of mixing uniformity after 30 minutes of mixing (3-1-1) Sample preparation [using component (a) as another component] The analytical sample was prepared in the same manner as in (1-1-1), except that it was mixed for 30 minutes. During the 30 minutes of mixing, the rotation direction was changed every 2 minutes for the first 10 minutes from the start of mixing, and the rotation direction was changed every 10 minutes after the first 10 minutes from the start of mixing. (3-1-2) Sample preparation [using component (b) as another component] The analytical sample was prepared in the same manner as in (1-1-2), except that it was mixed for 30 minutes. During the 30 minutes of mixing, the rotation direction was changed every 2 minutes for the first 10 minutes from the start of mixing, and the rotation direction was changed every 10 minutes after the 10 minutes from the start of mixing. (3-2-1) Quantitative determination and evaluation of elements in the sample [using component (a) as another component] In (1-2-1), the elements (Na, Mg) in the sample were quantified and their content (weight %) was calculated and evaluated in the same manner as in (1-2-1), except that the sample obtained in (3-1-1) was used. The results are shown in Table 3. (3-2-2) Quantitative determination and evaluation of elements in the sample [using component (b) as another component] In (1-2-2), the elements (Na, Cl, K) in the sample were quantified and their content (weight %) was calculated and evaluated in the same manner as in (1-2-2), except that the sample obtained in (3-1-2) was used. The results are shown in Table 4.

[0041] [Table 2]

[0042] [Table 3]

[0043] [Table 4]

[0044] The results shown in Tables 3 and 4 indicate that when using the PEGs from Examples 1 to 3, good mixing uniformity is achieved at all mixing times. This shows that excellent mixing uniformity is achieved even with short mixing times. When using the PEGs from Examples 4 and 5, there is room for improvement in mixing uniformity at short mixing times (2 minutes), but good mixing uniformity is achieved when the mixing time is 10 minutes or more. On the other hand, it can be seen that sufficient mixing uniformity is not achieved in Comparative Examples 1 and 2 even at long mixing times. Based on the above, the present invention provides polyethylene glycol with excellent mixing uniformity and a method for producing the same.

Claims

1. Polyethylene glycol having a number average molecular weight of 2000 to 10000, Polyethylene glycol in which the particle size D50 at which the cumulative volume from the smallest particles accounts for 50% of the volume frequency particle size distribution, as measured by laser diffraction scattering using a dry powder disperser, is between 100 μm and 250 μm.

2. The polyethylene glycol according to claim 1, wherein the particle size D10 at which the cumulative volume from the smallest particle side in the volume frequency particle size distribution, measured by laser diffraction scattering using a dry powder disperser, is 30 μm or more and 130 μm or less.

3. The polyethylene glycol according to claim 1 or 2, wherein the polyethylene glycol has a particle diameter D90 of 200 μm or more and 440 μm or less, at which the cumulative volume from the small particle side in the volume frequency particle size distribution, measured by laser diffraction scattering using a dry powder disperser, accounts for 90% of the total volume.

4. The polyethylene glycol according to claim 1 or 2, wherein the CV value of the polyethylene glycol measured by laser diffraction scattering using a dry powder disperser is 80% or less.

5. A method for producing polyethylene glycol according to claim 1 or 2, A method for producing polyethylene glycol, comprising a step of crushing polyethylene glycol having a number average molecular weight of 2,000 to 10,000 as a raw material.

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