UA48160C2 - Method of encapsulated pesticide and micro-capsule producing - Google Patents

Abstract

This invention relates to the microencapsulation of various materials, in particular pesticidal materials, to produce both wet and dry formulations. In particular, the invention relates to encapsulating such materials by incorporating a PVA into an interfacial polycondensation system for producing microcapsulcs, and subsequently spray drying the resulting microcapsules in the presence of the PVA, and optionally a further quantity of PVA which may be the same or different from the one adopted in the microencapsulation step, so that the encapsulated product can be diluted in water, in order to produce aqueous pesticidal compositions, which can be applied by conventional spray techniques.

Description

Description of the invention

This invention relates to the microencapsulation of various materials, in particular, pesticide materials, to produce both wet and dry compositions.

In particular, the invention relates to the encapsulation of such materials so that the product can be diluted with water to produce aqueous pesticide compositions that can be applied by conventional spraying methods.

Encapsulation of pesticides, plant growth regulators, etc. is an industry that has attracted growing interest in recent years. For safety and ease of distribution, such materials are particularly conveniently 710 supplied in the form of aqueous dispersions of solids that can be easily dispersed in water for use in the field.

Various proposals have been made in recent years in the field of microencapsulation of various pesticide materials.

For example, US patent Mo A-5160530 (in the name of Sigiep) describes a method of encapsulating pesticides (eg, trifluralin) by melting the active material and mixing the molten material with a film-forming polymer such as polyvinyl alcohol (PVA). After that, the materials are emulsified together and spray-dried.

US Patent No. 4,244,836 (Noesnzi) describes a similar method of encapsulating pesticide materials by spray drying a dispersion of active material and polyvinyl alcohol.

Although the methods described in these original sources are suitable for some systems, they have a number of disadvantages, such as the fact that the active material can diffuse into the product, resulting in the crystallization of the active material in the polyvinyl alcohol matrix, and that (especially in the Griffin method) that upon cooling to normal temperature, undesirable polymorphic modifications of the molten active material may form.

US patent MoA-4936901 (Mopzapio) describes another method of encapsulation, according to which microcapsules containing an active material are formed by carrying out an interphase polycondensation reaction using the mechanism of isocyanate interaction with polyamine. The resulting microcapsules with a polymerized interface are then subjected to spray drying. According to this original source, polyvinyl alcohol can be used as a suspension adjuvant in the spray drying stage. According to this method, microcapsules with uncontrolled release parameters are also obtained. In addition, some active materials show the ability to diffuse out of microcapsules with a polymerized interface during storage, which leads to crystallization (in the case of active substances that are in a solid state at moderate temperatures). Another complication associated with this method , is that all the obtained products have slow indicators - separation due to a significant distribution of particles by size and a thick polymer wall.

One of the problems that this primary source does not affect at all is the production of microcapsules that provide 325 rapid release of the active material, and not its prolonged or delayed release. Compositions with controlled release are often required to exhibit a rapid biological effect ("impact") followed by prolonged release ("retention") of the active substance. Capsules for rapid release are usually required to have small dimensions (typically a volume averaged diameter (VMA) of less than 5 " micrometers) or extremely thin polymer shell walls. None of the systems that were obtained under the patent of Z

USA Mo A-4936901, does not have the small particle size that is usually required to ensure a quick impact effect. the only one

In addition to the particle size information provided in this original source, the particle size distribution (not the volume-averaged diameter) ranges from 1 to 5 µm. Surface-active substances, which are essential for this source, belong to the type that is unsuitable for the formation of such capsules with a volume-averaged diameter of less than 5 micrometers. t- In addition, it is known, for example, from patents EP Mo A-0611253, US Mo A-5332584 and US Mo A-5324584,

Ge | the use of polyvinyl alcohols as surfactants or protective colloids in pesticide encapsulation processes. But in these sources, it is not assumed that polyvinyl alcohol takes an active part - in the formation of the wall of the shell, so that it can exert its influence and provide effective control over the release characteristics of the obtained microcapsules.

We have found that the introduction of polyvinyl alcohol into the interfacial polycondensation system to produce c microcapsules, followed by spray drying of the resulting microcapsules in the presence of PVA and, optionally, an additional amount of PVA, which may be the same or different from that used in the microencapsulation step , makes it possible to obtain microcapsules that have improved stability during storage, especially 25 according to the indicator of fading of the active material from the obtained microcapsules, in particular in the case of small ones

GF) microcapsules (for example, less than 5 micrometers). According to this, according to the first embodiment of the invention, a method of obtaining an encapsulated material is proposed, which includes the formation of microcapsules containing the material by an interphase polycondensation reaction, and spray drying of the obtained microcapsules in the presence of polyvinyl alcohol (PVA), and PVA is 60 present under reaction time of interphase polycondensation during the formation of microcapsules.

As mentioned above, an additional amount of PVA, which is preferably different from that used in the interfacial polycondensation step, can be added to the mixture containing the microcapsules before the spray drying step.

The PVA used in the microencapsulation step can be one that has a degree of polymerization of 50 to 5000 and a degree of hydrolysis of 7095 to 10095. Desirable properties for a PVA are that it should be an effective emulsifier before the polycondensation step, have the ability to promoting the stabilization of capsules during their formation, as well as having the ability to promote rewetting of capsules after spray drying when used as intended. One brand of PVA does not allow optimal satisfaction of all these requirements.

A material having a degree of polymerization of about 300 and a degree of hydrolysis of about 88,965 has been found to provide a good compromise.

Additional PVA, which may be added prior to the spray drying stage, is chosen mostly for its poor solubility of the encapsulated material and ease of rewetting with cold (and possibly hard) water. Chemically modified PVAs, such as 7/0 sulfonated or carboxylated PVAs, are particularly suitable for this purpose.

Interfacial polycondensation to form microcapsules can be accomplished by any of a variety of methods known to those skilled in the art.

In a preferred embodiment, the interfacial polycondensation reaction in the presence of PVA is carried out using a polyisocyanate and a polyamine. Because PVA is present during the 7/5 polycondensation reaction when the microcapsule walls are formed, and because it has a surface-active nature that ensures its high concentration and preferential orientation at the oil/water interface, PVA, having free

OH groups, reacts with isocyanate, which leads to the introduction of polyurethane groups to the polymer walls of the microcapsule. The permeability of polyurethane polymers is completely different from the indicators for polyurea, which is formed by the reaction of polyisocyanate with polyamine. other interfacial polycondensation reactions that may be used are, for example, isocyanate/polyol, isocyanate/water, and isocyanate/chloro-containing acid reactions.

Encapsulable material can be a pesticide material, for example:

F

- so zv " " and i s . Mr. so -

Fo s o yu 60 - - y y flufenoxuron profenofos y iya nn EI 111110 triagofos with the following fungicides: sch zv o o zo o - so zv - the following herbicides: « - s i

Etofumesate Pendimethalin 11111702 Trisluralin

Other pesticides can be used, such as the nitrification inhibitor nitrapyrin. The compositions of the invention may also contain mixtures of two or more pesticides, which in some embodiments may form a eutectic mixture having a melting point lower than the corresponding points of the individual components.

The pesticide may be a soluble organic solvent derivative of a pesticide compound that is itself sparingly soluble or insoluble.

The content of the active material can be, for example, from 30 to 90 95 wt., preferably from 60 to 85, even more preferably from 75 to 80 95 wt. from the mass of the spray-dried composition.

As indicated earlier, the method of the invention is particularly advantageous for the production of microcapsules having a small particle size, for example, those having a volume average diameter of 5 micrometers or less, preferably 2 micrometers or less. The main advantages of such small capsules are that they provide a larger specific surface per unit mass than large particles, and thus a higher release rate and an improved impact effect. In addition, such small capsules can penetrate the soil or through grass porosity better than larger capsules, and thus are more effective for some applications that require such mobility in soil or grass. Another advantage of such small capsules is that by reducing the size (from the volume-averaged diameter, it becomes possible to store a significantly increased amount of supercooled active substance in a liquid state. Thus, it becomes possible to reliably manufacture capsules with a liquid e, inside without using solvents, which in turn gives advantages from the point of view of ecology, as well as "-- ensures a higher content of the active substance in the finished product.

The presence of a liquid internal medium in capsules made using a supercooled active substance has several advantages, the most significant of which from the point of view of this invention is that, in general, a liquid internal medium will release the active substance faster than a solid. This, in combination with the small size of the particles, gives a significant increase in the rate of release of the active substance. A second advantage is that the internal medium does not crystallize, causing the capsules to rupture, which can lead to premature release and instability of the composition during storage. The third advantage of storing the active substance in the "liquid state" is that there is no possibility of formation of a less biologically active polymorphic modification due to crystallization - this problem is solved in another way in the US patent Mo A-5160530 (in the name of OGIAA) . Obviously, when the active substance is dissolved in a solvent, these problems do not arise. If the use of a solvent is considered desirable, any water-insoluble solvent can be used. Examples

Typical solvents are aromatic solvents, particularly alkyl-substituted benzenes, such as xylene or "propylbenzene" fractions, and mixed naphthalene and alkylnaphthalene fractions; mineral oils; kerosene, dialkylamides of fatty acids, such as dimethylamides of fatty acids, in particular dimethylamide of caprylic acid; chlorinated aliphatic and aromatic hydrocarbons, such as 1,1,1-trichloroethane and chlorobenzene, esters of glycol derivatives, such as acetate - n-butyl, ethyl or methyl ether of dipropylene glycol, ketones, such as isophorone and trimethylcyclohexanone (dihydroisophorone) and acetic esters acids such as hexyl or heptyl acetate. b Preferred organic liquids are xylene and propylbenzene fractions, alkyl acetates, and alkylnaphthalene fractions.

An advantage of the encapsulation method, in which polyvinyl alcohol is present during the encapsulation reaction, is that by changing the time period before the introduction of the polyamine, it is possible to control to some extent

The amount of polyurethane and polyurea in the walls of the capsule. Since these two polymers have very different diffusion coefficients of the encapsulated material, this polyurethane/polyurea ratio provides another

F, an independent method of controlling the rate of release of the active substance in addition to the control provided by adjusting the thickness of the capsule walls and the size of the capsules.

According to another embodiment, the solvent can be a polymerizable monomer, for example, an ethylenically unsaturated monomer (such as styrene, alpha-methylstyrene, (m)ethyl methacrylate, vinyl halide or acrylonitrile), which is subsequently polymerized to create a matrix of the internal environment of the capsules, which also provides it is possible to control the rate of release of the active substance.

Another advantage of the encapsulation method, according to which polyvinyl alcohol is present during the encapsulation reaction, is that due to the presence of a large number of OH groups, polyvinyl alcohol forms chemical bonds with the walls of the capsule during the shell formation reaction. Such binding leads to the formation of a certain amount of terminally attached PVA ("tails"), a certain amount of PVA attached at two points ("loops"), and a certain amount of PVA attached at several points ("chains"). The presence of unbound PVA, especially at the later stage of spray drying to obtain a dry product, can be a disadvantage. During spray drying, the concentration (of PVA, capsules and any added solutes) increases very quickly. The purpose of this is to create a uniform layer of water-soluble polymer around each capsule, which should form a film when dry. Obviously, as a result of the increase in concentration during the drying process, exhaustion flocculation may occur. At the same time, capsule-capsule contacts can be formed, which lead to irreversible coagulation. The presence of loops and chains largely protects against both of these causes of poor rewetting and colloidal instability. They also provide an additional 7/o significant advantage in that they allow the addition of a significant amount of electrolyte to the capsule suspension, which will facilitate rapid wetting of the dried product, as described in EP Mo A2-0568379 (to Kopyt and Naaghz). Addition of any high concentration of electrolyte to a normal capsule suspension generally causes irreversible coagulation of the capsules.

Another advantage of the encapsulation method according to the invention is that it allows to obtain dry compositions containing two or more active materials, and these materials are such that the direct manufacture of their composition (ie, without encapsulation of one or both of them) will lead to obtaining a product that will be chemically or physically unstable. Alternatively, said active substances may be encapsulated separately, but in a preferred alternative, one or more of the active materials (or a portion of one of the active materials) may be encapsulated by the method of the present invention, with the remainder remaining unencapsulated. . Thus, the unencapsulated active material will be bioavailable immediately after application, while the encapsulated material will be released more slowly. The amount of each of the materials used in these various forms will vary depending on the particular application, but in general each of such materials can be from 0.1 to 99.995 wt. from the total amount of encapsulated material. high school

Microcapsules according to the invention can be obtained by mixing with a high shear load a solution or melt containing an active material (for example, a pesticide), PVA (in the form of an aqueous solution) and one of the materials for interfacial polycondensation (for example, isocyanate). PVA acts as an emulsifier, and in some systems additional emulsifier may not be necessary. However, it is desirable to use additional emulsifiers, which may generally belong to the known type, to obtain the desired o

From the emulsion of small-sized particles. When the size of the emulsion particles reaches the desired value, a second polymeric crosslinking agent (for example, a polyamine) is added to complete the interfacial polycondensation. ise)

As indicated above, the preferred polycondensation reagent is a polyamine, which is usually a water-soluble reactive polyamine such as diethylenetriamine or tetraethylenepentamine. These amines react with isocyanate at the interfacial surface immediately after their introduction into the emulsion. More complete control can in some cases be achieved by using either a water-soluble or an oil-soluble salt of the amine, which is dissolved, respectively, in the water phase or in the oil phase at the initial stage of the process (eg, before emulsification). Because they are salts, they do not immediately react with the isocyanate, but readily do so after a pH has been established at which the free amine is released, resulting in crosslinking. "

High-shear mixing can be batch-wise or can be continuous (continuous). In the former case, the time of introduction or release of the reactive amine; is determined by the time required to carry out the technological process of emulsion formation with the desired particle size distribution (which obviously depends on the batch size), while in the second case

The interfacial reaction can be better controlled because amines can be added/released at any point in time by simply selecting the injection point on the process line, providing essentially complete control over the urea/urethane ratio. As mentioned above, the entire amount of PVA used in the process according to the invention to form microcapsules can be added at the beginning of the process. However, preference is usually given to the options according to which

After the formation of the microcapsules, but before spray drying, an additional amount of PVA is introduced. The quantitative ratio between the PVA introduced in the second stage to that which was added initially is typically not less than 0.5:1.

Other common additives such as emulsifiers, dispersants, dispersing agents, salts and film-forming polymers can also be added to the composition.

A number of preferred embodiments of the invention are described in the following Examples, and some of these Examples are illustrated in the accompanying drawings, wherein:

F) Figure 1 depicts the dependence of crystallinity on the value of the volume averaged diameter, and Figure 2 depicts the effect of crystallinity on the ability to remain.

Example 1 in The emulsion is obtained by mixing with a high shear load an aqueous solution of PVA (01 03, firm

Mirrop Sopvei, degree of hydrolysis 8895, degree of polymerization approximately 300) of a concentration of 2095 wt., which is maintained in a water bath at 55"C. Molten chlorpyrifos is mixed with polymeric isocyanate (MOKAMATE M220) in the amounts given below, and the mixture is added to the PVA solution in a water bath under conditions of high shear load. b5 - -

Chlorpyrifos technical 93.3g and and and and

For samples with a total mass of about 100g, a mixing time of about 30 seconds was sufficient to reduce the volume-averaged particle diameter below 1 micrometer, while for larger samples (500g) to achieve a volume-averaged diameter of about 1 micrometer it took about 90 seconds.

After reaching the desired value of the volume-averaged diameter, diethylenetriamine was added under conditions of /0 High shear load.

As a result of the reaction of isocyanate with polyamine and PVA, microcapsules containing the active substance dispersed in the aqueous phase were formed.

To obtain the dry product, the wet phase containing the capsules is then mixed (kg) with 0.855 kg of 103 in the form of 21956 aqueous solution and deionized water to set the viscosity of the solution to /5 suitable for spray drying (usually around 100 mPas) . The microcapsule suspension is spray-dried to give a dry product containing approximately 7595 wt. Chlorpyrifos. The amount of additional PVA was such that the ratio of the first portion to the additional portion of PVA in the dry product was approximately 6690 and 3390.

Spray drying was carried out at an inlet temperature of 1207 to 150"C and an outlet temperature of 657 to 85"C. The product is an off-white, free-flowing powder with a water content of approximately 0.595. The particle size (averaged by volume) of both the dry and liquid encapsulated product after dispersing the dry product in water was in both cases about 1 micrometer.

Testing the speed of allocation

The test of the release rate of the product was carried out by spraying the diluted composition, which contained 1000 ml of active material, on glass plates, and determining the amount that remained after the plates were stored in an environment with a constant temperature of 20 °C and a constant flow of air for 24 hours. For the product of Example 1, 9595 of the material remained on the glass plate. and)

Example 2

Wet capsules were obtained similarly to Example 1, but in a continuous mode using a "current" mixer, using the following composition of the composition: o - -

F

- so : : : o «

This wet phase containing the capsules (5 kg) was then mixed with 200 g of a 1095% solution of carboxylated PVA (trademark KM118) and spray-dried as described above to obtain a dry product containing approximately 7595 wt. Chlorpyrifos. The particle size (volume averaged) of both the dry and liquid encapsulated product after dispersing the dry product in water was in both cases about 0.6 µm. Glass plate residue tests for this product showed that only 3095 remained after -o storage for 24 hours, indicating the possibility of adjusting the selection parameters according to the present invention. The main differences between Examples 1 and 2 are as follows: (I) In Example 1, the isocyanate content is higher and, as a result, the walls are thicker than in Example 2. (I) The product of Example 1 has a larger volume-averaged diameter , than the product of Example 2, and thus a smaller value of the interfacial area, (NP) Since the product of Example 2 was obtained by a continuous process, and the product of Example 1 - (ee) batchwise, the amine of Example 2 was added earlier, than in Example 1. - (IM) Due to the larger particle size (volume-averaged diameter equal to 1 micrometer), the product of Example 1 has a greater degree of crystallinity than the product of Example 2, and near 1095 is (o) 50 in in solid form, compared to the values of a volume-averaged diameter of about 0.55 μm and a crystallinity bluntness of about 395 for Example 2.

Each of these factors leads to a higher release rate in Example 2 compared to Example 1, as clearly demonstrated by the significantly lower amount of active substance remaining after 24 hours, as

Example 2 compared to Example 1. An excellent correlation between the degree of crystallinity (90) and the 96 residue after 59 24 hours on a glass plate is shown in Figure 2.

GF) Examples 3-6 7 Using the same general method as described in Example 1, by changing the amount of materials other compositions characterized in Table 1 (amounts are given in grams) were prepared. In Table 1, we show how easy it is to adjust the output parameters. 5 bo Mogapaye 7.09 7.091 0.79) 0.79

00 ozmravsyuktovh ovi oo ov, penu vmu entn M/N Z shi 70 All these wet systems, which contain capsules, were mixed with 1 03 in a sufficient amount to obtain a product with a content of chlorpyrifos 75956 and dried by spraying in accordance with the above method. When conducting comparative studies using a nonionic surface-active substance with terminal methyl groups (AT OKH 48498) instead of PVA in the above Example 6, particles with a size of 0.45 microns were obtained. This product was spray dried unsuccessfully with a waxy 75 deposit in the spray dryer.

All products according to the invention according to Examples 1-6 were obtained by spray drying with a high yield and were stable during storage.

Examples 7-9

Three products were obtained according to the following recipe: - pi sch 29 All components were emulsified at a temperature of 50"C to obtain an emulsion, to which was then added: He) diethylenetriamine 1.90 g in 77.7 g of water.

In each of these Examples, the amount of time before the introduction of diethylenetriamine was varied in order to (av) change the ratio between polyurea and polyurethane in the capsule wall. This indicator was measured using the infrared measurement method. The separation rates for these three different batches were determined as previously described. "- so" - (minutes) micron urethane residue) vyyabv000000236111000yu a 1111bhvyliani 7 oil71111lev1111111111vBi ch sho | | - c It can be seen that changing the ratio of urea : urethane according to this technique is a useful tool that allows you to control the parameters of the product release. Similarly, a number of products were obtained in which the "z" release rate varied from about 10095 retention after 24 hours to less than 1095, simply by varying the urea:urethane ratio as described above.

Example 10 Chlorpyrifos-methyl was dissolved in an aromatic solvent (Zopimezzo 200) and then encapsulated according to the method described above, using the following formulation of the composition: (ee) -

Fo sz

This wet phase containing the capsules had a particle size (volume averaged) of 1.72 microns. Product 99 was mixed with a sufficient amount of PVA solution (0103) to obtain a dry product containing

GF) approximately 5095 wt. chlorpyrifos-methyl after spray drying, according to the method described above with 7 obtaining a free-flowing powder, which contains approximately 5095 wt. chlorpyrifos-methyl in the form of an encapsulated product. This product was shelf stable but readily released small capsules when added to water. After addition to water, the product had a particle size (volume averaged) of 1.66 microns, 60 demonstrating the ability of such products to redisperse when added to water to the particle size distribution of the wet product containing the capsules.

Example 11

A number of products containing chlorpyrifos with different particle size distributions were obtained and these products were stored at moderate temperature. Chlorpyrifos has a melting point of about 40-42 "C. At moderate temperatures, such encapsulated products can be expected to crystallize over time. The fact of crystallization can be established by differential scanning calorimetry (DSC), and the endothermic peak can be used to determine the amount of product in the crystallized state Using this technique, it was found that extremely low amounts of chlorpyrifos crystallized in the systems of the invention compared to the product obtained under US Patent No. 5,160,530 (in the name of sgInip), in which chlorpyrifos was emulsified in a PVA solution and then subjected to spray drying to obtain a dry product.Figure 1 shows the dependence of the determined crystallinity on the volume-averaged particle size for a number of compositions obtained according to the invention, compared to the corresponding Example obtained according to US Pat. Mo

A-5160530 ("Example according to Griffin"). It can be seen that the Griffin Example has a degree of crystallinity of about 3095 at 7/0 A volume averaged diameter of 0.4 micrometers, while the expected value for a material of this particle size encapsulated in accordance with the invention is about 395 It is obvious that the encapsulation leads to an unexpected stabilization of the metastable liquid state. The effect of crystallinity (and thus, indirectly, particle size) on retention rates is illustrated in Figure 2. For the products of the invention, a very low degree of crystallization is observed (up to 15956 for capsules with a volume-averaged /5 diameter of 2.2 microns), and for the product obtained by the Griffin method (which had a volume-averaged emulsion particle size of about 0.4 micrometers) - about 3090.

Claims (18)

The formula of the invention , and , , 1. The method of obtaining an encapsulated pesticide, which includes the formation of microcapsules containing a pesticide by an interphase polycondensation reaction that occurs in the presence of the first polyvinyl alcohol (PVA), which is used as an emulsifier before the polycondensation reaction, and adding, after the polycondensation reaction, an additional amount of the first PVA or of the second PVA and spray drying of the resulting mixture containing microcapsules. 2. The method according to claim 1, in which the additional amount of PVA added before the specified stage (o) of spray drying is different from the PVA that was used during interphase polycondensation. 3. The method according to any of the previous items, in which the first PVA has a degree of hydrolysis from 70 to 10095 and a degree of polymerization of at least 50. 4. The method according to claim 3, in which the first PVA has a degree of hydrolysis of 8895 and a degree of polymerization of 300. 5. The method according to any of the previous items, in which the second PVA is carboxylated or sulfonylated PVE. "- 6. The method according to any of the previous items, in which microcapsules are formed by the reaction of polyisocyanate with polyamine. co 7. The method according to any of the previous items, in which the content of the encapsulated material is from 30 to 95 wt. 9o from the total mass of spray-dried microcapsules. 8. The method according to claim 7, in which the content of the encapsulated material is from 60 to 85 wt. 95 from the total mass of spray-dried microcapsules. 9. The method according to claim 7, in which the content of the encapsulated material is from 75 to 80 wt. 95 of the total « 70 Masses of spray-dried microcapsules. w-in the village 10. The method according to any of the previous items, in which the spray-dried microcapsules have a volume-averaged particle size of 5 micrometers or less. :with" 11. The method according to claim 10, in which the spray-dried microcapsules have a volume-averaged particle size of 2 micrometers or less. 12. The method according to any of the previous items, in which the pesticide to be encapsulated is in the form of a solution in a solvent. 13. The method according to any of the previous items, in which the specified pesticide can be a mixture of at least two different pesticides. - 14. Microcapsules obtained by forming microcapsules containing a pesticide by an interfacial polycondensation reaction that occurs in the presence of a first polyvinyl alcohol (PVA) used as (2) an emulsifier before the polycondensation reaction, and adding an additional amount of the first PVA after the polycondensation reaction or a second PVA and spray drying the resulting mixture containing microcapsules. 15. Microcapsules according to claim 14, in which the encapsulated material is in the microcapsules in a liquid state. 16. Microcapsules according to claim 14 or claim 15, which contain at least two different pesticides. 17. Microcapsules according to claim 16, in which at least two different pesticides are encapsulated separately. 18. Microcapsules according to claim 16 or claim 17, which contain microcapsules with both relatively slow and relatively (F) fast release. name) 60 b5