EP1154760A1

EP1154760A1 - Biodegradable composite material for the production of microcapsules

Info

Publication number: EP1154760A1
Application number: EP00925026A
Authority: EP
Inventors: Marianne Teller; Hans-Werner Heinrich; Joachim Teller; Udo Meyer
Original assignee: Bioserv AG
Current assignee: Bioserv AG
Priority date: 1999-02-19
Filing date: 2000-02-20
Publication date: 2001-11-21
Also published as: CN1339964A; DE10008880A1; CA2362263A1; RU2001125666A; US20020147296A1; AU4390200A; JP2002537415A; WO2000048573A1

Abstract

The invention relates to a biodegradable polymeric composite material for the production of microcapsules containing any type of substances, e.g. foodstuffs, medicine and immunogens or technical materials such as oils, colorants, enzymes and the like. According to the invention, a polymeric composition of general formula R1n-P?1-(Q-P2)¿i-R2m is provided, wherein P?1 and P2¿ represent the same or different macromolecular structures; R?1 and R2¿ represent the same or different end groups or protective groups or receptor molecule or marker; i, n and m are natural numbers and can individually be zero or one and Q represents an at least bifunctional structure with hydrophilic properties derived from the polyols, polyamides and polyesters, wherein the composition has an enzymatic recognition site and/or interface for splitting the bonds between substructures R, P and/or inside Q.

Description

Biodegradable composites for the production of microcapsules

The invention relates to biodegradable polymer composites for the production of microcapsules of any ingredients, such as e.g. Food, pharmaceuticals and immunogens or materials of the art such as e.g. Oils, dyes, enzymes etc.

The encapsulation of liquid or solid substances to protect against external influences and in the form of small particles or capsules plays a major role for different areas of application, for example in the food industry, pharmacy and technology. The physical, chemical and biological properties of the microparticles are determined by

• the technology of manufacture (spray drying, coacervation, extrusion, encapsulation (emulsion and dispersion process), copolymerization, micronization through supercritical gases)

• The matrix, shell / capsule materials used (mono-, di- and polysaccharides, proteins, polyamino acids, polycarboxylic acids, poly (lactide-co-glycolide), acrylates, polyalcohols and their copolymers, liposomes, silicate, etc. in various combinations and mixing ratios ) and

Possible surface modification (immunoglobulins, lectins, poly (ethylene glycol), ganglioside GM1, pharmacologically active compounds)

While the technologies for producing small capsules or particles are state of the art, new capsule materials are being sought for the ever-growing fields of application.

In particular, for the targeted release of medicinal products, solutions are sought which protect the encapsulated active ingredient from external influences, as

Transport vehicle functions in the intended area of activity and only at the destination

Active ingredient releases.

US Pat. No. 5,700,486 discloses biodegradable polymers or copolymers in pharmaceutical compositions for the formation of particles which are used for the controlled release of pharmacologically active substances. The compositions listed consistently represent physical mixtures of the uniform polymers and copolymers, the proportions of which are varied before the encapsulation process. The disadvantage of such biodegradable polymers is that the substance release is neither targeted nor by defined enzyme action.

US-A 5,686,113 describes the microencapsulation in aqueous solutions. The biodegradable capsule material used is a mixture of an anionic polymer or its salts and an amino-functionalized monomer, the formation of the Reaction product takes place during the microencapsulation. Such mixtures have the disadvantage that the formation reaction of microcapsules cannot take place simultaneously in aqueous and also in non-aqueous systems. With the surface modifications described, the particles can bind selectively to certain ligands, but a specific dissolution of the capsule wall at the binding site is not possible.

The object of the invention is to find biodegradable components which allow a technically simple process for the production of microcapsules of any ingredients and both for the temporary separation of any materials, such as e.g. Oils, dyes, enzymes, drugs, immunogens, nucleic acids, etc. from the surrounding environment, as well as or for a targeted transport and controllable release of active pharmaceutical ingredients.

Surprisingly, a polymer composite is suitable as the capsule wall material, which is a uniform reaction product and has covalent bonds between the substructures, at least one of the components used having hydrophilic properties. This composite allows the formation of microcapsules from solid or dissolved substances or preparations in both aqueous and non-aqueous systems.

The biodegradable polymers according to the invention only bind to defined ligands and are only broken down into subunits under the influence of known factors. The new polymers can be used for different applications.

Capsule materials are produced which bind to target cells according to their intended use, can be absorbed by them or dissolve on the cell surface or inside the cell. This basic concept of the chemical connection of non-degradable or poorly degradable substances with substances that are specifically split by certain enzymes (composites) is used for a wide variety of biological and technical fields of application

- Use of these new materials

- variations in particle size (nm - μm)

- Multi-layer capsule wall design using different composites and

- Using different methods of microparticle production by "core-shell encapsulation" or copolymerization, new types of drug transport systems are created. Through targeted surface modification and selection of interfaces that can only be split by defined endogenous or enzymes from pathogens, it was possible to to achieve particularly high concentrations of active substances in locations with pathological reaction patterns.

Composites of the general formula are preferred

R ^l _n _ p ^l _ (Q _ p ² ₎ . _ _R ² _m where

P ¹ and P ² for identical or different macromolecular structures, preferably from the

Areas of polyester, polyamides or polysaccharides,

R ¹ and R ² denote the same or different end groups or protective groups or receptor molecules or markers, i, n and m are from the range of natural numbers and can assume zero or one in individual cases,

Q is an at least bifunctional structure with hydrophilic properties, derived from the

Fields of polyols, polyamides and polyesters, means used as capsule wall material, which is used to split the bonds between the

Substructures R, P and / or as well as within Q an enzymatic recognition and / or

Have interface.

Polymers with structural elements of hydroxycarboxylic acids, their salts or esters are particularly preferred for P ¹ and P ". They are preferably polyesters, such as polyglycolides, polylactides, poly (hydroxybutyric acids) or copolymers resulting therefrom, polysaccharides, such as polygalacturonic acid or alginic acid. The end or protective groups R ¹ and / or R ² are acyl, alkyl or alkoxycarbonyl groups In another embodiment variant, R ¹ and / or R ^{2 are} markers, receptors or other molecules which bind specifically to structures, preferably from the substance classes of the oligopeptides, proteins, glycoproteins and oligonucleotides Receptor molecules are preferably lectins, receptor ligands or antibodies.

Compounds which are derived from mono-, oligo- or polysaccharides and which optionally have amino or carboxy groups or for compounds which are derived from di-, oligo- or polypeptides are particularly suitable as structural element Q. The structural element Q preferably has enzyme recognition and cut parts, preferably it has a di- or polysaccharide. or an oligopeptide with a defined protease interface.

Mixtures of composites in which i = zero or i = 1 are particularly preferably used as encapsulation material. According to the invention, the composite material according to the invention is used to produce microcapsules of substances, for example pollutants, such as mineral oil, for temporary separation from the surrounding environment.

The use of the composites according to the invention with different marker or receptor molecules R ¹ and / or R ² has the advantage that they recognize extracellular and / or intracellular structures. Through the use of the composites and through the connection of a marker via molecular recognition, a targeted transport and a targeted release of active substances can take place at the site of action of immunologically and or pharmacologically / toxicically active substances.

The production of microcapsules with any ingredients, e.g. Solid or dissolved materials from the fields of food, pharmaceutical preparations or technical products or additives using the composites according to the invention are carried out according to processes known per se in organic solvents or aqueous emulsions, e.g. through core-shell processes.

Preferred composites can be found in Table 1 below.

Abbreviations:

Ac-PLA 17000 O-acetyl polylactide 17000

Ac-PLA 2000 O-acetyl polylactide 2000

BSA Bovine Serum Albumin

ClAc-PLA 2000 O-chloroacetyl polylactide 2000

DBU 1,8-diazabicyclo [5.4.0] undec-7-ene

DMAP 4-Dtmethyl-ammopyridine

EDC N-ethyl-N '- (3-dimethylaminopropyl) carbodiimide hydrochloride

Lectin Lectin UEA I (Ulex Europaeus)

MS-PLA 2000 O-maleoyl polylactide 2000

MES buffer morpholino ethanesulfonic acid

PGAS polygalacturonic acid 25000 - 50000

PLA 17000 polylactide 17000

PLA 2000 polylactide 2000

PGlu polyglutamic acid 2000 - 15000 Example 1: Composite of O-acetyl polylactide 2000 and dilysin

Solutions of EDC (95.6 mg in 1 ml water) and DMAP (122 mg in 2 ml acetonitrile) are added in one portion to a solution of Ac-PLA 2000 (1 g) in acetonitrile (40 ml). The reaction mixture is activated for 30 min at RT in an ultrasonic bath. A solution of H-Lys-Lys-OH ^• 2 HCl (80.3 mg in 2 ml of water) is added to the activated mixture and the entire batch is stirred at 50 ° C. for 2 h. The reaction mixture is then concentrated in vacuo to about 10 ml. The remaining oil is first washed with 30 ml ethanol / water (v / v: 50/50). The solid formed is centrifuged (5000 rpm, 5 min), washed with 20 ml of water, centrifuged again and dried in vacuo.

IR spectrum: 3342, 3335 (NR), 1759 (ester), 1647 (amide)

1H-NMR: δ = 1.44-1.61 (m, CH ₃ ), 2.58-3.27 (m, CH ₂ ), 5.08-5.15 (m, CH), 6.58-6.61 (m, NH), 8.15-8.17 (m, NH); ¹³ C-NMR: δ = 14.6, 15.5, 16.5, 17.6, 20.4, 20.5 (CH ₃ , PLA), 25.6, 34.9, 35.5, 36.7 (CH ₂ ), 39.5, 40.9, 43.1 (CH), 55.6 (CH ₂ ), 68.9 (CH, PLA), 106.5, 143.6 (CH), 169.5, 169.6, 169.8, 170.3 (CO, PLA), 175.0 (COOH, PLA), 175.8 (COOH)

Example 2: Composite of O-acetyl polylactide 2000 and dihistidine

Solutions of EDC (95.6 mg in 1 ml water) and DMAP (122 mg in 2 ml acetonitrile) are added in one portion to a solution of Ac-PLA 2000 (1 g) in acetonitrile (40 ml). The reaction mixture is activated for 30 min at RT in an ultrasonic bath. A solution of H-His-His-OH ^• trifluoroacetic acid (101.6 mg in 2 ml of water) is added to the activated mixture and the entire batch is stirred at 50 ° C. for 2 h. The reaction mixture is then concentrated in vacuo to about 10 ml. The remaining oil is first washed with 30 ml of ethanol / water (50/50). The solid formed is centrifuged (5000 rpm, 5 min), washed with 20 ml of water, centrifuged again and dried in vacuo. IR spectrum: 3504, 3496 (NH), 1759 (ester), 1648 (amide)

Example 3: Composite of O-chloroacetyl polylactide 17000 and a cysteine-rich peptide

A solution of H-Lys-Cys-Thr-Cys-Cys-Ala-OH ^• trifluoroacetic acid (25 mg in 1 ml of water) and DBU (20 μl.) Are added to a solution of ClAc-PLA 17000 (1.73 g in 50 ml of acetonitrile) ) and stirred at 50 ° C for 3 h. The reaction mixture is then concentrated in vacuo to about 10 ml. The remaining oil is washed with 40 ml ethanol / water (50/50) and the solution carefully poured off. This procedure is repeated with 30 ml of ethanol and the product is dried in vacuo. Elemental analysis: calculated: N 0.19; found: N 0.25 IR spectrum: 3504 (NH), 1751 (ester), 1648 (amide)

Example 4: Composite of polygalacturonic acid and dilysin

BrCN solution (35 μl, c = 0.1 g / 1 in acetonitrile) is diluted in 10 ml of water and added dropwise to a solution of polygalacturonic acid (1.25 g) in Na ₂ CO ₃ buffer (100 ml). After stirring for 15 min, a solution of H-Lys-Lys-OH ^• 2 HCl (5,335 mg) in water (5 ml) is added and the reaction mixture is stirred overnight at room temperature. The product is precipitated with ethanol, centrifuged (4000 rpm, 5 min) and freeze-dried. IR spectrum: 3600-3100 (OH, NH), 1606 (bs sh, COOH, COO ^~ amide), 1098 (COC)

Example 5: Composite of polygalacturonic acid and dihistidine

BrCN solution (35 μl, c = 0.1 g / 1 in acetonitrile) is diluted in 10 ml of water and added dropwise to a solution of polygalacturonic acid (1.25 g) in Na ₂ CO ₃ buffer (100 ml). After stirring for 15 min, a solution of H-His-His-OH ^• trifluoroacetic acid (6.24 mg) in water (5 ml) is added and the reaction mixture is stirred overnight at room temperature. The product is precipitated with ethanol, centrifuged (4000 rpm, 5 min) and freeze-dried. IR spectrum: 3600-3100 (OH, NH), 1608 (bs sh, COOH, COO ^~ amide), 1098 (COC)

Example 6: Composite of polyglutamic acid and dihistidine

Polyglutamic acid (100 mg) is suspended in acetonitrile (10 ml). Solutions of EDC (2.24 mg in 1 ml water) and DMAP (2.144 mg in 1 ml acetonitrile) are added in one portion. The mixture is activated at 30 ° C in an ultrasonic bath for 30 min. A solution of H-His-His-OH ^■ trifluoroacetic acid (2.4 mg) in water (1 ml) is added and the mixture is stirred at 50 ° C. for 2 h. The solid is then centrifuged (4000 rpm, 5 min), washed with 5 ml of ethanol / water (50/50) and centrifuged again. This procedure is repeated with 5 ml of water. The product is then freeze-dried. IR spectrum: 3342, 3287 (NH), 1733 (CO), 1645 (amide)

Example 7: Composite of O-acetyl polylactide 2000 and lactose

To a solution of Ac-PLA 2000 (1.0 g) in acetonitrile (150 ml), solutions of EDC (960 mg in 5 ml water) and DMAP (610 mg in 10 ml acetonitrile) are added in one portion. The reaction mixture is activated for 30 min at room temperature in an ultrasonic bath. A solution of lactose (1.8 g in 25 ml of water) is added to the activated mixture and the mixture is stirred at 50 ° C. for 2 h. The reaction mixture is then concentrated in vacuo to about 20 ml. The remaining residue is washed with 100 ml of water, centrifuged (3500 rpm, 10 min) and dried in vacuo.

NMR NMR: δ = 1.13-1.35 (m, CH ₃ ), 1.45-1.62 (m, CH _: -, PLA), 2.10 (s, CH ₃ ), 2.57-2.71 (m, CH), 3.17 (s, CH), 4.30-4.37 (m, CH), 5.10-5.19 (CH. PLA); ^ι:, C-NMR: δ = 14.6, 16.6, 16.7. 17.4, 20.5 (CH ₃ ), 39.8, 42.77, 42.81, 43.0 (CH), 66-6, 68.2, 68.5, 68.7, 68.8, 68.9, 69.1, 69.4, (CH), 169.16, 169.2, 169.3, 169.6, 169.7 , 170.3, 170.4 (C = O), 175.2 (COOH)

Example 8: Composite of O-acetyl polylactide 17000 and lactose

Solutions of EDC (96 mg in 1 ml water) and DMAP (61 mg in 1 ml acetonitrile) are added in one portion to a solution of Ac-PLA 17000 (8.5 g) in acetonitrile (100 ml). The reaction mixture is activated for 30 min at RT in an ultrasonic bath. A solution of lactose (90 mg in 5 ml of water) is added to the activated mixture and the mixture is stirred at 50 ° C. for 2 h. The reaction mixture is then concentrated in vacuo to about 20 ml. The remaining residue is washed with 100 ml of ethanol / water (50/50) and the solution carefully poured off. This procedure is repeated with 100 ml of ethanol / water (50/50) and 50 ml of ethanol. The product is then dried in vacuo.

Η NMR: δ = 1.18-1.26 (m, CH ₃ ), 1.41-1.56 (m, CH ₃ , PLA), 1.98 (s, CH ₃ ), 2.70 (s, CH), 3.12 (s, CH), 3.68 (dd, CH), 4.13-4.21 (m, CH), 4.29-4.37 (m, CH), 5.06-5.23 (CH, PLA); ¹³ C-NMR: δ = 14.0, 16.6, 16.7, 18.4, 20.5 (CH ₃ ), 58.3, 61.5 (CH ₂ ), 66.57, 66.63, 68.9, 69.1, 69.2, 69.4 (CH), 169.1, 169.2, 169.3, 169.4, 169.5 (C = O) MALDI-TOF-MS: confirms the structure AcO-PLA-lactose-PLA-OAc

Example 9: Composite of O-acetyl polylactide 2000 and dextran 6000

Solutions of EDC (95.6 mg in 1 ml water) and DMAP (61 mg in 1 ml acetonitrile) are added in one portion to a solution of Ac-PLA2000 (1 g) in acetonitrile (40 ml). A solution of dextran 6000 (3 g) in water is added to the mixture and the entire batch is stirred at 50 ° C. for 2 h. A white precipitate precipitates, which is centrifuged (3000 rpm, 10 min) and washed with 40 ml of water. The mixture is then centrifuged again and the solid is dried in vacuo.

Η NMR: δ = 1.44, 1.46 (CH ₃ , PLA), 3.04-3.71 (m, CH, CH ₂ , dextran), 4.66 (bd), 5.15-5.22 (m, CH, PLA); ¹³ C-NMR: δ = 16.7 (CH ₃ ), 66.2 (CH ₂ ), 68.9, 70.3, 70.6, 72.0, 72.7, 73.5, 98.4 (CH), 169.4 (C = O)

Example 10: Composite of O-Maleoyl-polylactide 2000 and the lectin UEA I

MS-PLA2000 (0.736 mg) and EDC (0.269 mg) are suspended in 0.1 M MES buffer solution (1 ml) and activated for 30 min at room temperature in an ultrasonic bath. The lectin UEA I (10 mg) is added and the mixture is shaken at room temperature for 2 h. The solid is then centrifuged (3000 rpm, 10 min), washed twice with water and freeze-dried.

Example 11: Composite of O-Maleoyl-Polylactid 2000 and Albumin (BSA) MS-PLA2000 (0.736 mg) and EDC (0.269 mg) are suspended in 0.1 M MES buffer solution (1 ml) and activated for 30 min at room temperature in an ultrasonic bath. BSA (20 mg) is added and the mixture is shaken at room temperature for 2 hours. The solid is then centrifuged (3000 rpm, 10 min), washed twice with water and freeze-dried.

Example 12: Microencapsulation of a Rabbit IgG preparation with a composite according to Example 8

1 g of a lyophilized Rabbit IgG preparation (grain size 1 to 5 μm) is suspended in 100 ml of petroleum ether (80 - 110 ° C) by stirring. A solution of 1 g of composite from Example 8 and 5 ml of acetone in 10 portions is added dropwise within 5 h. Allow to stir for another hour. After sedimentation, the suspension is filtered, washed with 20 ml of petroleum ether and air-dried.

For a comparative analysis of the mode of action of an enzymatic interface, polylactide 17000 and the corresponding composite material according to Example 8 were used as

Envelope material used and treated analogously.

The release studies are carried out in an incubation shaker at 37 ° C in PBS buffer at pH 7.3. 200 mg of particles are suspended in 10 ml of PBS buffer. To study the

Influence of the enzyme on the stability of the particle shell is ß-

Galactosidase (20 units) added. 500 μl of solution are removed at intervals of 30 min, centrifuged at 5000 rpm for 5 min and the supernatant for the rabbit content

IgG analyzed by ELISA.

The results are summarized in Fig. 1 and 2.

Example 13: Microencapsulation of albumin (BSA) with a composite according to Example 7

1 g of composite according to Example 7 is dissolved in 10 ml of methylene chloride. A solution of 20 mg BSA in 500 μl water is added with dispersing. The emulsion is added dropwise at 500 1 / min to 300 ml of a 1% polyvinyl alcohol solution. The mixture is stirred for 30 min, centrifuged at 1800 rpm for 5 min. The supernatant solution is separated off. The particles are resuspended with a little water, centrifuged again and dried in vacuo.

Example 14: Microencapsulation of albumin (BSA) with a composite according to Example 7 by means of spray drying

400 mg BSA are dissolved in 200 ml water. A solution of 20 g composite according to Example 7 is dispersed in 100 ml methylene chloride in such a way that the methylene chloride almost completely evaporated and a stable emulsion is formed. This emulsion is then spray dried.

Device conditions: inlet temperature 93 ° C, outlet temperature 63-66 ° C, aspirator: 98%, pump: 10%

Example 15: Core-Shell Encapsulation of Rabbit IgG / PLA 17000 Cores with Composites According to Example 10

1 g of Rabbit IgG / PLA 17000 cores (produced in analogy to Example 12, d = 1-10 μm) are resuspended in 50 ml of petroleum ether (80-110 ° C.) with stirring. A solution of 0.05 g of composite according to Example 10 and 0.05 g of PLA 17000 in 2 ml of acetone is added dropwise. Allow to stir for another hour. After sedimentation, the suspension is filtered, washed with 20 ml of petroleum ether and air-dried.

The resuspended particles agglutinate with anti-Ulex-coated, fluorescent silicate particles (d = 800 nm) quantitatively.

Example 16: Microencapsulation of silicate particles (impregnated with amaranth) with a composite according to Example 7

Synthetic silicate particles (d = 800 nm) are used as the core material. 2 g of silicate particles are shaken in an aqueous amaranth solution (50 mg / 50 ml of water) for 10 minutes, centrifuged and dried. 1 g of these particles are suspended in 100 ml of petroleum ether (80-110 ° C). A solution of 1 g of composite from Example 7 and 5 ml of acetone in 10 portions is added dropwise within 5 h. Allow to stir for another hour. After sedimentation, the suspension is filtered, washed with 20 ml of petroleum ether and air-dried.

The release studies are carried out in an incubation shaker at 37 ° C in PBS buffer at pH 7.3. 200 mg of particles are suspended in 10 ml of PBS buffer. To study the influence of the enzyme on the stability of the particle shell, ß-galactosidase (20 units) is added before the particle is added. 500 μl of solution are removed at intervals of 30 minutes and analyzed for the content of amaranth by spectrophotometry at a wavelength of 520 nm. The results are summarized in Fig. 3.

Claims

claims

1. Biodegradable polymer composites for the production of microcapsules from solid or dissolved substances or preparations in organic solvents or aqueous emulsions, characterized in that they have a polymeric composition of the general formula

R ^, _n - P ¹ - (Q - P ² ) _I - R ² _ra , where P ¹ and P ² stand for identical or different macromolecular structures,

R ¹ and R ^{2 are the} same or different end groups or protective groups or

Receptor molecules or markers mean i, n and m are from the range of natural numbers and can assume zero or one in individual cases, and

Q denotes an at least bifunctional structure with hydrophilic properties, derived from the areas of polyols, polyamides and polyesters, the composition for cleaving the bonds between the substructures R,

P and / or within Q has an enzymatic recognition and / or interface.

2. Composites according to claim 1, characterized in that P ¹ and P ^" polymers with structural elements from the fields of polyester, polyamides / amines or polysaccharides or of hydroxycarboxylic acids, their salts or esters.

3. Composites according to claim 2, characterized in that polyesters are polyglycolides, polylactides, poly (hydroxybutyric acids) or copolymers resulting therefrom.

4. Composites according to claim 2, characterized in that polysaccharides are polygalacturonic acid or alginic acid.

5. Composites according to claim 1 to 5, characterized in that the end or protective groups R ¹ and / or R ^{2 are} acyl, - alkyl or alkoxycarbonyl groups.

6. Composites according to claim 1 to 5, characterized in that R ¹ and / or R ^" markers. Receptor or otherwise represent molecules specifically binding to structures, preferably from the substance classes of the oligopeptides, proteins, glycoproteins and oligonucleotides.

7. Composites according to claims 1-6, characterized in that the structural element Q stands for a compound which is derived from mono-, oligo- or polysaccharides which optionally have amino or carboxy groups, or that Q stands for a compound derived from di-, oligo- or polypeptides.

8. Composites according to claim 1 to 7, characterized in that the structural element Q is a molecule that can be cleaved by enzymes.

9. Composite according to claim 8, characterized in that the structural element Q has a di or polysaccharide.

10. Composite according to claim 8, characterized in that the structural element Q has an oligopeptide with a defined protease interface.

11. Composites according to claim 1 to 10, characterized in that compounds of the general formula are used in which i = zero or i = 1.

12. Use of polymeric composite material according to claim 1 to 11 for the temporary separation of substances from the surrounding environment.

13. Use according to claim 12 in a plurality of sleeves with different enzyme recognition and interfaces.

14. Use according to claim 12 and 13 with different marker or receptor molecules R ¹ and or R ² .

15. Use according to claim 14 with different marker or receptor molecules R ¹ and / or R ² , which recognize extra- and / or intracellular structures.

16. Use of composites after 12 to 15 for the targeted transport and release of immunologically and / or pharmacologically / toxic substances.

17. A process for the preparation of microcapsules from solid or dissolved substances or preparations, characterized in that composites according to claims 1 to 1 1 are dissolved in organic solvents or aqueous emulsions are prepared therefrom and the encapsulation is carried out according to techniques known per se.