Spherical microparticles with polyester walls

Abstract

The present invention relates to compositions of spherical microparticles composed of a wall material and at least one cavity that comprises a gas and/or a liquid, which have pores on the surface thereof, wherein the spherical microparticles have a mean particle diameter of 10-600 μm and wherein at least 80% of those microparticles, the particle diameter of which does not deviate from the mean particle diameter of the microparticles of the composition by more than 20%, each have on average at least 10 pores, the diameter of which is in the range from 1/5000 to ⅕ of the mean particle diameter, and, furthermore, the diameter of each of these pores is at least 20 nm, wherein the wall material consists of a composition comprising at least one aliphatic-aromatic polyester, and the wall material has a solubility at 25° C. of at least 50 g/l in dichloromethane, a method for the preparation thereof and also the use thereof.

Claims

1. A composition consisting essentially of spherical microparticles composed of a wall material and at least one cavity that comprises a gas and/or a liquid, which have pores on the surface thereof, wherein the spherical microparticles have a mean particle diameter of 10-600 gm; and wherein at least 80% of microparticles whose particle diameter does not deviate from the mean particle diameter of the microparticles of the composition by more than 20%, each have on average at least 10 pores with a diameter in the range from 1/5000 to ⅕ of the mean particle diameter, with the proviso that the diameter of each of the at least 10 pores is at least 20 nm, wherein the wall material is formed of a composition comprising at least one aliphatic-aromatic polyester selected from the group consisting of polybutylene azelate-co-butylene terephthalate (PBAzeT), polybutylene brassylate-co-butylene terephthalate (PBBrasT), polybutylene adipate terephthalate (P BAT), polybutylene sebacate terephthalate (PBSeT) and polybutylene succinate terephthalate (PBST), wherein the wall material has a solubility in dichloromethane of at least 50 g/l at 25° C.; and wherein the pores are in the walls of the microparticles.

2. The composition of spherical microparticles according to claim 1, wherein the composition forming the wall material comprises at least one polymer having a glass transition temperature or a melting point in the range from 45 to 140° C.

3. The composition of spherical microparticles according to claim 1, wherein the wall material is formed of a composition comprising the at least one aliphatic-aromatic polyester and also at least one further polymer selected from the group consisting of polyacrylate, polyamide, polycarbonate, polystyrene, aliphatic-aliphatic polyester, aromatic-aromatic polyester, polyolefin, polyurea and polyurethane.

4. The composition of spherical microparticles according to claim 1, wherein the wall material is formed of a composition comprising the at least one aliphatic-aromatic polyester and also at least one aliphatic-aliphatic polyester.

5. A carrier substance for filling with at least one aroma chemical comprising the spherical microparticles according to claim 1.

6. A perfume, washing or cleaning agent, cosmetic agent, body care agent, hygiene article, food, food supplement, scent dispenser or fragrance comprising the composition according to claim 1.

7. An agent composition comprising the composition according to claim 1, in a proportion by weight of 0.01 to 99.9 wt % based on the total weight of the composition.

8. A method for controlled release of aroma chemicals comprising utilizing the composition according to claim 1.

9. A liquid suspension comprising the composition according to claim 1.

10. The liquid suspension of according to claim 9, wherein the spherical microparticles are suspended in an aqueous suspension.

11. The composition according to claim 1, wherein the wall material is formed of a composition comprising the at least one aliphatic-aromatic polyester and at least one further polymer is selected from the group consisting of polyacrylate, polyamide, polycarbonate, polystyrene, aliphatic-aliphatic polyester, aromatic-aromatic polyester, polyolefin, polyurea, and polyurethane, and wherein the proportion of the at least one aliphatic-aromatic polyester is 30 to 99 wt % based on the total weight of the at least one aliphatic-aromatic polyester and the at least one further polymer.

12. The composition of spherical microparticles according to claim 11, wherein the aliphatic-aliphatic polyester is selected from the group consisting of polylactide, polylactic acid copolymers, and poly(lactic-co-glycolic acids).

Description

EXAMPLES

(1) The examples below are intended to illustrate the invention in more detail. The percentages in the examples are weight percentages unless otherwise indicated.

(2) Determining the mean particle diameter in aqueous suspension/emulsion using light scattering: The particle diameter of the w/o/w emulsion or the particle suspension is determined with a Malvern Mastersizer 2000 from Malvern Instruments, England, sample dispersion unit Hydro 2000S according to a standard measurement method which is documented in the literature. The value D[4,3] is the volume-weighted average.

(3) Determining the Mean Particle Diameter of the Solid:

(4) The microparticles are determined as powder with a Malvern Mastersizer 2000 from Malvern Instruments, England, including powder feed unit Scirocco 2000 according to a standard measurement method which is documented in the literature. The value D[4,3] is the volume-weighted average.

(5) Determining the Pore Diameter:

(6) The pore diameters were determined by means of scanning electron microscopy (Phenom Pro X). For this purpose, various close-up images were taken and these were retrospectively automatically measured using the ProSuite (FibreMetric) software from Phenom. The pores of a selected region of a particle were identified using the difference in contrast and the surfaces thereof were automatically measured. The diameter for each surface was calculated with the assumption that the surfaces were circular. (Sample size 100 pores).

(7) In the context of the evaluation, only those pores whose pore diameter was at least 20 nm were taken into consideration. Depending on the particle size, the images were recorded, for larger particles with 1600- to 2400-times magnification, and for smaller particles with up to 8000-times magnification.

(8) In order to determine the size of at least 10 pores, only those microparticles whose particle diameter does not deviate from the mean particle diameter of the composition of microparticles by more than 20% were taken into consideration.

(9) The following assumptions were made for evaluation of the number of pores based on the total surface area of the microparticle: Since these are spherical particles, the image only shows half the surface of the particle. If the image of a microparticle shows at least 5 pores whose diameter is at least 20 nm and whose diameter is in the range from 1/5000 to ⅕ of the mean particle diameter, then the total surface comprises at least 10 pores.

(10) The evaluation was carried out according to the following procedure:

(11) 1. The mean particle diameter D[4,3] of the microparticles was already determined in the microparticle dispersion, using light scattering. The upper and lower limits of the particle diameter of the microparticles which are taken into consideration for determining the pores (±20%) can be calculated from this.

(12) 2. The microparticle dispersion was dried.

(13) 3. From a sample, in each case 20 images showing multiple microparticles were taken by means of scanning electron microscopy.

(14) 4. 20 microparticles were selected whose particle diameter is in the range ±20% of the mean particle diameter of the microparticles. The particle diameter thereof was thus measured with the ProSuite (FibreMetric) software from Phenom.

(15) 5. The pores of each of these 20 microparticles were measured. For this purpose, the surface areas of the visible pores were measured automatically and the diameter thereof was calculated.

(16) 6. The individual values of the pore diameters were checked as to whether their diameter met the condition of being in the range from 1/5000 to ⅕ of the mean particle diameter and being at least 20 nm.

(17) 7. The number of pores meeting this condition was determined and multiplied by two.

(18) 8. It was verified whether at least 16 microparticles had on average at least 10 pores.

(19) Determining the Bulk Density:

(20) The bulk density was determined as specified in DIN-EN ISO 60: 1999;

(21) Determining the Water Content of the Microparticle Composition

(22) Karl Fischer titration (DIN 51777): For this, approx. 2 g of powder were precisely weighed in and titrated with a 799 GPT titrino by the Karl-Fischer method.

(23) Abbreviations: PBSeT—polybutylene sebacate terephthalate PBAT—polybutylene adipate terephthalate PLA—polylactide PS—polystyrene PC—polycarbonate PBA—polybutylene adipate PLGA—polylactide-co-glycolide PVA—polyvinyl alcohol

Example 1: Procedure for Preparing the Fillable Spherical Microparticles

(24) Pore former solution: 0.5 g of ammonium carbonate were dissolved in 54.0 g of water (pore former).

(25) Solution of the aliphatic-aromatic polyester: 21.6 g of PBSeT were stirred into 270.0 g of dichloromethane and dissolved at 25° C. while stirring.

(26) In order to prepare the w/o emulsion, 54.5 g of pore former solution were emulsified in the solution of the aliphatic-aromatic polyester for 1 minute at 10 000 rpm with a rotor-stator.

(27) The resultant w/o emulsion was transferred into the polyvinyl alcohol solution (having a degree of hydrolysis of 88 mol % and a viscosity of 25 mPa*s and proportion of carboxyl groups of 3 mol %) and likewise emulsified with shear and energy input (one minute at 10 000 rpm with a rotor-stator).

(28) The w/o/w emulsion produced in this way was subsequently further stirred at 150 rpm with an anchor stirrer, heated slowly to 40° C. while being stirred, and kept at this temperature for 4 hours with a nitrogen flow of 100 I/hour. Thereafter, the microparticle suspension was cooled to room temperature and freeze-dried.

(29) The particle diameter after freeze-drying was 5 μm,

(30) Water content: 0.5%

Examples 2 to 4 and 6 to 7

(31) Analogously to example 1, fillable spherical microparticles were prepared with the remaining pore formers given in table 1 at the respective concentrations and also the polymer mixtures given in table 1 (made of aliphatic-aromatic polyester and a further polymer).

Example 5

(32) Analogously to example 1, spherical microparticles were prepared, with the difference that for producing the w/o/w emulsion, emulsification was carried out with an anchor stirrer at 150 rpm.

(33) TABLE-US-00001 TABLE 1 Fillable spherical microparticles using various pore formers Concentration Mean of pore former particle diameter Ex. Pore former [wt %] Polymer D[4,3] [μm].sup.1) 1 Ammonium carbonate 0.5 PBSeT 5 2 Ammonium 1.0 Mixture (55% PBAT 42 hydrogencarbonate with 45% PLA) 3 Sucrose 1.0 Mixture (55% PBAT 9 with 45% PLA) 4 Sucrose 10.0 Mixture (55% PBAT 8 with 45% PLA) 5 Ammonium sulfate 40.0 PBSeT 200 6 Sodium chloride 10.0 Mixture (55% PBAT 11 with 45% PLA) 7 Ammonium 1.0 Mixture (55% PBAT 48 oxalate with 45% PLA) .sup.1)Determining the particle diameter of the microparticle in the aqueous suspension.

Examples 8, 11 and 12

(34) The procedure was conducted analogously to example 1, with the difference that the polymer mixtures found in table 2 were used.

Examples 9 and 10

(35) The procedure was conducted analogously to example 5, with the difference that the polymer mixtures found in table 2 were used.

(36) TABLE-US-00002 TABLE 2 Fillable spherical microparticles using various polymers Mean particle diameter Example Polymer D[4,3] [μm].sup.1) 8 Mixture (55% PBSeT + 45% PLA) 11 9 Mixture 90% PBSeT + 10% PS 200 10 Mixture (70% PBSeT + 30% PC) 250 11 Mixture (50% PBSeT + 50% PBA) 8 12 Mixture (55% PBSeT + 45% PLGA) 5 .sup.1)Determining the particle diameter of the microparticle in the aqueous suspension.

Example 13-20 Preparation of Various Particle Sizes

(37) 21.6 g of PBSeT were stirred into 270.0 g of dichloromethane and dissolved at 25° C. while stirring. 54.5 g of pore former solution (5 g ammonium carbonate dissolved in 54.0 g water) were emulsified in this solution for 1 minute at 10 000 rpm with a rotor-stator.

(38) The resultant w/o emulsion was transferred into the polyvinyl alcohol solution (having a degree of hydrolysis of 88 mol % and a viscosity of 25 mPa*s and proportion of carboxyl groups of 3 mol %) and likewise emulsified with shear and energy input (found in table 3).

(39) The w/o/w emulsion produced in this way was subsequently further stirred at 150 rpm with an anchor stirrer, heated slowly to 40° C. while being stirred, and kept at this temperature for 4 hours with a nitrogen flow of 100 l/hour. Thereafter, the microparticle suspension was cooled to room temperature and freeze-dried.

(40) TABLE-US-00003 TABLE 3 Emulsification of the w/o emulsion in water to give the w/o/w emulsion Mean Emulsifying Duration [min] at particle diameter Example apparatus rpm [μm].sup.1) 13 Anchor stirrer 1 min, 800 rpm 500 14 Rotor-stator 1 min at 3500 rpm 130 15 Rotor-stator 1 min at 6000 rpm 75 16 Rotor-stator 1 min at 10 000 rpm 6 17 Rotor-stator 1 min at 15 000 rpm 4 18 Rotor-stator 1 min at 20 000 rpm 2 19 Rotor-stator 1 min at 26 000 rpm 2.5 20 Ultrasound 1 min at 400 W, 24 kHz 1.0 rpm: revolutions per minute .sup.1)Determining the particle diameter of the microparticle in the aqueous suspension.

(41) General Procedure: Filling and Closing the Capsules

(42) 20 g of the fillable spherical microparticles obtained from example 5 were stirred with 40 g of a solution of an aroma chemical (see table 4) on a roller mixer for five hours.

(43) Subsequently, the entire suspension was heated to 60° C. (jacket temperature) and kept at this temperature for five hours. This suspension was then cooled to room temperature, filtered and rinsed three times with ethanol. Subsequently, the microparticles were dried for four hours in a drying oven at 40° C.

(44) According to this procedure, the filled microparticles of examples 21 to 23 were obtained.

(45) The loading of the microparticles was calculated as follows:
Loading [%]=(weight loaded M−weight unloaded M).Math.100/weight loaded M

(46) M: microparticles

(47) TABLE-US-00004 TABLE 4 Concentration Loading of of the aroma the micro- Exam- Aroma chemical particles ple chemical Solvent [wt %] [%] 21 L-Menthol 1,2-propylene 10 44 glycol 22 Rose Oxide 1,2-propylene 10 52 glycol 23 Dihydrorosan 1,2-propylene 10 50 glycol

Example 24: Procedure for Preparing Fillable Spherical Microparticles (Small Particles)

(48) Pore Former: Ammonium Sulfate

(49) Solution of the aliphatic-aromatic polyester: 1.8 g of PBSeT were stirred into 22.5 g of dichloromethane and dissolved at 25° C. while stirring.

(50) In order to prepare the w/o emulsion, 4.5 g of a 0.5% pore former solution were emulsified in the solution of the aliphatic-aromatic polyester for 1 minute at 10 000 rpm with a rotor-stator.

(51) The resultant w/o emulsion was transferred into the polyvinyl alcohol solution (having a degree of hydrolysis of 88 mol % and a viscosity of 25 mPa*s and proportion of carboxyl groups of 3 mol %) and likewise emulsified with shear and energy input (one minute at 8 000 rpm with a rotor-stator).

(52) The w/o/w emulsion produced in this way was subsequently further stirred at 400 rpm with an anchor stirrer and kept at 25° C. for 4 hours with a nitrogen flow of 60 l/hour.

(53) The mean particle diameter of the microparticles D[4,3] was 11.1 μm. Pores were only measured from those microparticles whose particle diameter was in the range from 9.99 to 12.21 μm as determined by scanning electron microscopy. The lower limit calculated for pores that met this condition was 0.02 μm and the upper limit was 2.22 μm. Evaluation of the SEM images showed that the measured microparticles each had more than 5 pores in the image that met the condition, and thus on average more than 10 pores on the surface of each microparticle. The number of pores was also met for the preferred pore size range 4/100 to ⅕ of the mean particle diameter (calculated lower and upper limits: 0.44 μm to 2.22 μm).

Examples 25-28

(54) Analogously to example 5, spherical microparticles were prepared, with the difference that the pore formers given in table 5 were used instead of ammonium sulfate.

(55) TABLE-US-00005 TABLE 5 Fillable spherical microparticles using various pore formers Concentration Mean of pore former particle diameter Ex. Pore former [% by wt.] Polymer D [4,3] .sup.1) [μm] 25 Ammonium carbonate 1.0 Mixture (55% PBAT 150 with 45% PLA)  .sub. 26 .sup.2) — 1.0 Mixture (55% PBAT 104 with 45% PLA) 27 — — Mixture (55% PBAT 155 with 45% PLA) 28 Ammonium carbonate  0.25 Mixture (55% PBAT 399 with 45% PLA) .sup.1) Determining the particle diameter of the microparticle in the aqueous suspension. .sup.2) Water-soluble pore formers were not used, rather the surfactant sorbitan monooleate (Span 80) was used.

(56) TABLE-US-00006 TABLE 6 Detailled characterization of spherical microparticles using various pore formers Smallest and largest pore Calculated upper and lower limits Mean particle diameter measured [μm] of the pore diameter [μm] Number of Ex. diameter [μm] min max Lower limit.sup.1) Upper limit.sup.2) pores ≥10 25 150 0.3 4.94 0.03 30.0 Met 26 104 2.0 12.8 0.02 20.8 Met 27 155 0.3 2.8 0.31 31.0 Met 28 399 0.9 6 0.08 79.8 Met .sup.1)1/5000 of the mean particle diameter of the microparticles .sup.2)1/5 of the mean particle diameter of the microparticles

Examples 29-31: Filling and Closing the Microparticles

(57) 20 g of each of the fillable spherical microparticles obtained from examples 25-27 were stirred with 40 g of a solution of an aroma chemical mixture on a roller mixer for five hours. Subsequently, the entire suspension was heated to 60° C. and kept at this temperature for five hours. This suspension was then cooled to room temperature, filtered and rinsed three times with a 10 wt % aqueous propanediol solution. Subsequently, the microparticles were dried for four hours in a drying oven at 40° C.

(58) The loading of the microparticles was calculated as follows:
Loading [%]=(weight loaded M−weight unloaded M).Math.100/weight loaded M
M: microparticles

(59) TABLE-US-00007 TABLE 7 Filling Capsules used Loading of the Example (example no.) microparticles [%] 29 25 74 30 26 65 31 27 69

(60) The filled microparticles according to the invention demonstrate good loading. Furthermore, they have good storability, especially with respect to moisture. The preferred microparticles with small pores of examples 25 and 27 also especially have good tightness.