DD148926A1 - CHEMICAL PRAEPARATES WITH INCREASED FLUID COMPOSITION AND A METHOD OF PREPARING THEM - Google Patents

Abstract

The invention relates to a powder or paste preparation which forms a stable dispersion in the aqueous medium and in which the particles of the water-insoluble or sparingly soluble component or components are coated with water-soluble polymer or a polymer mixture. Furthermore, the invention relates to a method for improving the beating capacity of the solid particles dispersed in aqueous medium, in which the water-insoluble or sparingly soluble particles are coated with a water-soluble polymer or polymer mixture before being dispersed. The process according to the invention can be used, for example, in the pharmaceutical industry, in the preparation of crop protection agents, in the cosmetic or in the dyestuff industry for the production of aqueous suspensions which are distinguished by a high stability.

Description

12 835 55

21 8863-1-

Increased fluidity chemical preparation and method of making the same

Field of application of the invention:

The invention relates to a chemical product with increased flexibility and a method for producing the same.

Characteristic of the known technical solutions:

In various fields of chemistry, such as in the pharmaceutical industry, in the pesticide industry, in the cosmetics industry and in the dye industry, the problem frequently arises of ensuring a good stability of aqueous suspensions or a homogeneous concentration of the active ingredient.

The sedimentation or creaming is more usually reduced by an increase in the viscosity of the outer phase of the suspension with the aid of macromolecules, which

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dissolve in the outer phase or swell in this. These macromolecules are to be used in relatively high concentrations «

It is also known from colloid literature (Alfred Kuhn: Handbuch der Kolloid-Chemie, 1963) that the water-soluble macromolecules exert a protective colloid effect in a generally very low concentration.

The stabilizing effect of the polymers on the colloidal sols is explained in particular by the change in the adsorption ratios below:

The macromolecule, which stabilizes the dispersion from a certain concentration, at a concentration, which is smaller than the critical, causes a reduction in stability and exerts a so-called sensitizing effect. This so-called eensitizing concentration depends inter alia on the quality of the polymer.

Object of the invention:

The invention is intended to improve the settling ability of water-dispersed solid particles.

presentation; of the invention:

The invention has for its object to provide preparations available, which ensure a stable aqueous dispersion. In connection with this, a method for producing these preparations should be further provided.

The invention is based on the finding that, even in the case of the aqueous dispersions, the particles containing a pulverulent polymer and containing larger particles than the colloids

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the powders associated with the adsorption of the polymer appear phenomena.

Due to theoretical considerations, it has been recognized that an intermediate state causing instability of a suspension does not occur when the particles are completely coated with the polymer from the beginning.

According to the invention, the powder or paste preparations forming a stable dispersion in the aqueous medium are prepared by coating the water-insoluble or soluble particles of the solid component or components with a water-soluble polymer or polymer mixture, if necessary simultaneously or subsequently dries and the resulting powder or the phase obtained if desired3 converted by the addition of known additives in pharmaceutical preparations, pesticides, cosmetic products, dyes or X-ray contrast agents.

As the water-soluble polymers, polyvinyl alcohol, polyvinylpyrrolidone, ethyl cellulose, carboxyethylethylcellulose sodium or a mixture thereof may be used. The polymer is used in a concentration at which greater than the sensitizing concentration is achieved after the dispersion of the powder or powder mixture in the outer phase. For example, polyvinyl alcohol prepared from at least 40 % hydrolyzed polyvinyl acetate is used in a concentration of 10 to 10 g / l and polyvinylpyrrolidone is preferably used in a concentration of 10 to 10 g / l. When working with methylcellulose, the concentration is between 10 and 10 g / l.

The water-insoluble or sparingly soluble component or the corresponding components may consist of one or more active pharmaceutical ingredients and, if desired, excipients customary in pharmacy or

consist of one or more plant protection products - active substances and, where appropriate, excipients or auxiliary substances customary in the crop protection industry. It is also possible to use cosmetic substances and, if desired, additives customary in the cosmetic industry or else dyes and conventional auxiliaries customary in the dye industry or also X-ray contrast substances and customary corresponding additives.

As a solid component, for example, a chemotherapeutic agent, e.g. a nitrofuran derivative, preferably 3- (5-nitro-furylideneamino) -2-oxazolidinone (furazolidone). As a fixed component, you can use ^. Example, a herbicidal, fungicidal, acaricidal, growth-regulating, or nematozides agent can be used. As the herbicidally active benzoic acid derivative, e.g. 2,5-dichloro-3-amino-benzoic acid, etc. Likewise, herbicidal active compounds of the general formula I or a mixture thereof can be used.

In the formula I stands

R is an optionally substituted by a heterocyclic radical alkyl, cycloalkyl or an optionally substituted by halogen and / or alkyl and / or haloalkyl and / or alkoxy and / or alkyl mercapto aryl or aralkyl,

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R is hydrogen or alkyl, where R and R together with the nitrogen atom to which they are attached can form an optionally N- or O-atom-containing heterocyclic ring,

R is optionally substituted by halogen-substituted alkyl, and

R ^ is hydrogen or alkyl. ,

Examples are methyl-N- / 3-N '~ 3 ^I methyl-phenyl- (carbamoyloxy) ethyl phenyl7carbamat and W / 3- (N'-phenyl-car-

218863

bamoyloxy) phenyl7carbamate (drodin). As the insecticidal agent, a benzofuran derivative such as 2,3-dihydro-2,2-dimethyl-7-benzofurahiolmethylcarbamate (carbofuran) can be used.

As the solid component, an inorganic extender or metal oxide, e.g. the barium sulfate usable as the X-ray contrast agent or the titanium dioxide used in the dyestuff industry.

The protective effect polymer is applied to the surface of the particles of the water-insoluble or sparingly soluble dispersible solid powders or powder mixtures from the solution of the polymer by plating, wetting with solvent and spraying. These operations can be carried out simultaneously with the drying. The drying can also be done later. The application and drying can thus be combined into one operation, whereby the process can be carried out continuously. For applying the polymer or the various polymers, V / asser,. organic solvent, e.g. Aliphatic alcohol, ketone, ether or a mixture thereof and a mixture of water and the above-mentioned organic solvents are used.

It is also possible to prepare the solid particles in the solution of the polymer. In another embodiment, the coated particles are prepared by drying, fluidizing or spray-drying the solution containing the solid granules and the polymer or polymers. The particles to be coated may also be desired to be formed in such a way that the individual components from the solution or from a melt or from the liquid state at room temperature are previously applied to a water-insoluble carrier. The superfluous solvent can be removed if necessary.

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The further processing and formulation of the polymer-coated particles can be achieved, if desired, by the use of other additives and e.g. done by grinding. The coated particles may be mixed with other additives, e.g. with water or with water-miscible organic solvents, possibly with a mixture of water and organic solvent, processed to a paste (concentrated suspension) v / earth. The paste can be prepared by mixing the remaining additives, e.g. surface-active substances, dyes, surfactants, pH adjuster are dissolved or dispersed in a liquid phase and the powder consisting of the coated particles is mixed with this solution.

The solid particles may also be coated with the polymer by forming a paste from the finely granulated solid or a mixture thereof and a concentrated solution of the polymer in water, organic solvent or solvent mixture.

The solid particles take up the polymer from the concentrated solution during the panning.

The liquid phase used during the paste formation may also contain the other necessary additives.

Ausführun ^ sbeispiele:

The advantages of the invention will be explained in more detail with reference to the following examples. The settling ability of the 0.5% aqueous dispersion (based on the active ingredient) was used as a characteristic property. For comparison, the settling ability of preparations containing no polymer but tested under the same conditions and otherwise the same composition is determined.

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on iron. The beating capacity was determined in tap water. The stabilizing concentration of the polymers listed in the examples was determined in a separate test series.

The examples show that the preparations according to the invention show a beating capacity which is better by 2 to 10% than the preparations which do not contain the polymer but which are otherwise identical and which have a beating capacity of 1 to 8 % better than the preparations in which the polymer was not previously applied.

It should be emphasized that the invention is not limited to the pesticides mentioned in the examples. Rather, the process may be applied to any water-insoluble or sparingly soluble, room temperature, solid material from which a stable aqueous dispersion is to be prepared for any purpose.

example 1

Active ingredient: 3- (5-nitrofurylideneamino) -2-oxazolidinone Polymer: Polyvinylpyrrolidone in 8 / Siger ethanoleth

solution

Dispersant: Tensopol SP USP (Na-Pett3äurealcoholsulphonat).

Additive against sticking together the granules of the powder preparation: Aerosil

Preparation: 80 % furazolidone-containing dispersible powder.

To fine powder of 'furazolidone is added such an amount of the polymer solution that the total amount of the polymer - based on 80 % active ingredient of the preparation - 2 %

The suspension is homogenized and concentrated vigorously. To 82 % powder are added 15 % dispersant and 3 % aerosol.

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sil, to prevent sticking together. The mixture is ground. A homogeneous flowable and suspendable powder is obtained. To a product without polymer is added 17 % dispersant

Beating capacity: without polymer 83 %

with polymer in the form

of a powder 85 %

90 % according to the invention

Example 2

Active ingredient: 3 ~ (5-nitrofurylideneamino) -2-oxazolidinone Product: 50 % dispersible powder

The procedure is as in Example 1, with the difference that -man used in addition to the active ingredient as an excipient finely powdered dry kaolin, so that the active ingredient content based on the total weight of the preparation - 50 ^c and the kaolin content is 30 %

Beating capacity: without polymer 69 %

with polymer in the form ·

a powder 79%

80 % according to the invention

Example β

Active ingredient: 3- (5-nitrofurylideneamino) -2-oxazolidinone Product: 40 % dispersible paste

$ 3.85 PVP is dissolved in 96.15 % anhydrous glycerol with mild heating. To a solution of PVP in 86.7 parts by weight of glycerol are added 13 * 3 parts by weight of surface-active agent, and it forms a homogeneous solution with mild heating. Composition of Surfactant: 13.6 parts by weight Span 20 (sorbitan lionolaurate),

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2T 8863

86.4 parts by weight Tween 20 (polyoxyethylene sorbitan LIonolaurat). With 60 parts by weight of polymer and surface-active mixture enthaltexidem glycerol 40 parts by weight of the finely pulverized active ingredient are mixed. The mixture is homogenized. A paste is obtained.

Beating capacity: without polymer 84 %

90 % according to the invention

Example 4

Active ingredient: 2,5-dichloro-3-aminobenzoic acid Product: 80 % dispersible powder Method according to Example 1

Beating capacity: without polymer 82 %

with polymer in the form

of a powder 86 %

according to example 4 92 %

Example 5

Active ingredient: 2,5-Dichloro-3-amino-benzoic acid Product: 50 % pure paste

The procedure is as described in Example 1, with the difference that the surfactant used is Tween. 50 parts by weight of the finely powdered active ingredient are dispersed in 50 parts by weight of the non-acidic glycerol containing the polymer and the surface-active agent and are converted into a paste by homogenization. Polymer content of the product: 1.7 % · Beating capacity: without polymer 82 %

according to example 98 %

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Example 6

Active ingredient: 2,5-dichloro-3-amino-benzoic acid Product: 50 % paste

The active ingredient is coated with PVP according to Example 1. The coated drug thus obtained is pulverized. In 86,7. Parts by weight of anhydrous glycerol is dissolved with mild heating 13.3 parts by wt. Tween 80 surfactant. 54 parts by weight of the polymer-coated active ingredient with fine Granulen.werden converted into 46 parts by weight of surfactant-containing anhydrous glycerin in a smooth paste. Beating capacity: without. Polymer 82 %

after example 6 97 %

Example 7

Active substance: 2,5-dichloro-3-aminobenzoic acid Preparation: 80 / Siges dispersible powder

The procedure is as in Example 1, but instead of the ethanolic solution of PVP, a 4% strength distillate aqueous solution of polyvinyl alcohol (hydrolyzed in 98 %, water-soluble) is used,

The coating polymer is polyvinyl alcohol. Beating capacity: without polymer 82 %

with powdery polymer 83 % according to Example 7 89 %

Example 8

Active ingredient: 2,3-dihydro-2,2-dimethyl-7-ben7, ofuranol-methyl

-carbamate Product: 45 saw paste

218863

Polymer: PVP *

Surfactant mixture · Brij 35 (polyoxyethylene lauryl ether)

33.3 parts by weight

Mirj 51 (polyoxyethylene stearate)

66.7 parts by weight, homogenized by heating.

In 57.5 parts by weight of butyl glycol (butyl cellosolve) is dissolved with heating 42.5 parts by weight of PVP. To 85.32 parts by weight of the solution are added 14.68 parts by weight of surfactant mixture. The mixture is homogenized with heating. This gives a thick paste. , -.

Beating capacity: without polymer 85 %

according to example 8 94 %

Example ft

Main component: barium sulphate

Product: 80% diopergable powder

Polymer: CarboxymethylcelluloGO-lia in 2 z

distilled / aqueous solution.

The product is prepared according to Example 1, with the difference that PVP CLIC-Na is used as the coating polymer.

Beating capacity: without polymer 32, 5 %

with powdered polymer 38.0 % according to Example 9 42.6%

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Example 10 .

Active ingredient: Methyl-1 ^ - / 3- (N ^T -3 '-methylphenyl- (carbamoyloxy) -phenyl-7-carbamate and ethyl-N- / 3- (N'-phenyl-carbamoyloxy) -phenyl-7-carbamate in a 50:50 homogeneous mixture

Product: 80% dispersible powder Polymer: PVP, in 8 / Siger ethanolic solution Surfactants:

Atlox 4862 and Na lauryl sulphate: Additives to prevent sticking of the powder: Aerosil

The product is prepared as in Example 1 except that the PVP is added so that the ratio of the PVP and the powder mixture is 3 % : 80 % . Atlox 4862 is used in an amount of 11 parts by weight, Na lauryl sulphate of 3 parts by weight and Aerosil of 3 parts by weight.

Beat capacity: without polymer 91.9 %

with powdery polymer 92.7 %

93.5 % by the process according to the invention

Example 11

Main component: titanium dioxide

Product: 80 / dispersible powder

A fine powder (80 parts by weight) of the main component is mixed with a 5 / Sigen CMC-Na solution in an amount such that the amount of CMC-Na is 20 parts by weight. The suspension is homogenized and dried. Beating capacity: without polymer 5.0 %

with powdered polymer 6.0 / 5

according to the process of the invention 8.2 %

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Example 12

On 58 parts by weight of finely powdered diatomaceous earth is used 10 parts by weight of dimethyl phthalate. A dry powdery product is obtained. In 200 parts by weight of a 4% aqueous solution of PVP, the product is suspended. The suspension is dried in vacuo. 11.6 parts by weight of Atlas Renex 35 and 8.4 parts by weight of Tensopol SP USP dispersant and 5 parts by weight of hydrophilic Aerosil are added to the powder. After grinding and homogenization, fine, easily flowing powder is obtained. Beating capacity: without polymer 70.1 %

with powdery !.

Polymer. 78.3 %

84.0% according to the process of the invention

Example 13

To a 10 parts by weight of barium chloride and 1 part by weight of PVP-containing aqueous solution is added with stirring dilute sulfuric acid in an equimolar amount (based on barium chloride). The precipitated Bariurnculphat is concentrated. To 82 parts by weight of PVP-containing barium sulphate powder, 15 parts by weight of Tensopol SP USP dispersant and 3 parts by weight of additive Aerosil (to prevent sticking together) are ground and homogenized to give a fine powder

Beating capacity: without polymer 32.5 %

with powdery

Polymer 39.3 %

prepared according to Example 13 44.2 %.

Claims (39)

- U - 218863 Invention claim :. , " 1. A chemical, in a aqueous Medirjü a stable dispersion forming powder or paste preparation, characterized in that the granules of the water-insoluble or sparingly soluble solid component or components with a water-soluble polymer or a water-soluble polymer mixture coated wind. , 2. Preparation nach'Punkt 1, characterized in that the granules are coated with Polyvinylalkohl, polyvinylpyrrolidone, Me methyl cellulose or carboxymethylcellulose sodium or with a mixture derselbe.n. Preparation according to items 1 and 2, characterized in that the polymer or the polymer mixture is present in the preparation in a concentration which, after dispersion in the external phase, ensures a higher concentration than the sentient concentration, i. that this polyvinyl alcohol is preferably greater than 10 to 10 g / l, _5 in the case of polyvinylpyrrolidone, preferably higher than 10 to 10 g / l and in the case of methyl cellulose preferably higher than 10 ~ ⁴ to 10 g / l. 4 · preparation according to items 1 to 3, characterized in that the granules of the solid component or components are applied to a water-insoluble carrier. 5. Preparation according to claim 1, characterized in that the solid component is formed by one or more pharmaceutical excipients and, if desired, pharmaceutically acceptable additives. 6. A preparation according to item 1 and 5, characterized in that the solid component is a chemotherapeutic agent. -is- 218863 7. A preparation according to item 1 and 6, characterized in that the chemotherapeutic agent is an iJ-furofuran derivative. 8. A preparation according to item 1 and 7, characterized in that the nitrofuran derivative is 3- (5-nitrofurylideneamino) -2-oxazolidinone. 9. A preparation according to item 1, characterized in that the solid component is formed by one or more crop protection agents and, if desired, the customary in crop protection agents Ililfsstoffe, 10. A preparation according to item 1 and 9, characterized in that the herbicidal agent is a benzoic acid derivative. 11. Preparation according to items 1 and 9 »characterized in that the solid component is a herbicides, fungicides, growth regulators, acaricides or nematocides. 12 * Preparation according to items 1 and 10, characterized in that the benzoic acid derivative is 2,5-dichloro-3-amino-benzoic acid. 13. A preparation according to item 1 and 10, characterized in that the herbicidal agent is a compound or mixture of the compounds of general formula I, wherein R is optionally substituted by a heterocyclic radical alkyl, cycloalkyl, optionally substituted by halogen and / or alkyl, and and / or haloalkyl and / or alkoxy and / or alkylmercapto-substituted aryl or aralkyl and R is hydrogen or alkyl, 1 2 R and R may form, with the nitrogen atom to which they are attached, a heterocyclic ring optionally containing IJ or O atoms, - 16 - - 16, 3 218863 represents optionally halogen-substituted alkyl and R Y / oxygen or alkyl. 14. The preparation according to items 1 and 13 »characterized in that the herbicidal composition is a mixture of Iaethyl-N- / 3-N'-3- ^t- methylphenyl (carbamoyloxy) phenyl] jiarbamate and ethyl N- / 3- ( n ·-phenylcarbamoyloxy) phenyl / tarbamate. The preparation according to 1 and 10, characterized in that the insecticidal agent is a benzofuran derivative. 16. A preparation according to item 1 and 15 »characterized in that the benzofuran derivative is 2,3-dihydro-2,2-dimethyl-7-benzofuranol methylcarbamate. 17. A preparation according to item 1, characterized in that the solid component is an inorganic extender. 18. A preparation according to item 1, characterized in that the solid component is barium sulfate. Preparation according to item 1, characterized in that the solid component is a metal oxide. 20. A preparation according to item 1, characterized in that the solid component is titanium oxide. 21. A process for preparing a powder or paste preparation forming a stable dispersion in an aqueous medium, characterized in that the particles of the water-insoluble or soluble solid component or components are coated with a water-soluble polymer or polymer mixture and dried simultaneously or subsequently and the powder or paste thus obtained, if desired, by adding 218863 would be processed from known additives to pharmaceutical preparations, pesticides, cosmetics, dyes or Röntgenkontra3tstoffen. 22. The method according to item 21, characterized in that one uses as the polymer polyvinyl alcohol, polyvinylpyrrolidone, methyl cellulose or carboxymethyl cellulose sodium or a mixture thereof. Method according to item 21, characterized in that the solid component (s) is / are used or previously applied to a water-insoluble carrier and then used or vided. 24. The method according to item 21, characterized in that one or more pharmaceutical active ingredients and desired case α pharmaceutically customary auxiliaries used as a solid component. 25. The method according to item 1 and 2, characterized in that one uses as a solid component a chemotherapeutic agent. 26. The method according to item 21 and 25, characterized in that one uses as a chemotherapeutic agent a nitrofuran derivative. 27. The method according to item 21 and 26, characterized in that one uses as nitrofuran derivative 3- (5-nitrofurylideneamino) -2-oxazolidinone. 28. The method according to item 21, characterized in that verv / ends as a solid component one or more crop protection agents and, if desired, the usual additives in the crop protection industry. 216863 Method according to points 21 and 28, characterized in that the solid component used is a controlling, herbicidal, insecticidal, fungicidal, acaricidal or nematocidal agent. 30. The method of item 21 and 29 », characterized in that the herbicidal agent used is a benzoic acid derivative. 31. The method of item 21 and 30, characterized in that is used as the benzoic acid derivative 2,5-dichloro-3-aminobenzoic acid. 32. The method according to item 21 and 29, characterized in that as a herbicidal agent, a compound of the general formula I or the mixture thereof, wherein R is optionally substituted by a heterocyclic radical alkyl, cycloalkyl, optionally substituted by halogen and / or alkyl, and / or haloalkyl and / or alkoxy and / or alkyl mercapto aryl or aralkyl and
2 R is hydrogen or alkyl, 1 2 R and R with the nitrogen atom to which they are attached are able to form a heterocyclic ring optionally containing N or O atoms, 3 K is optionally substituted by halogen alkyl and R ^ is hydrogen or alkyl. 33. Method according to items 21 and 32, characterized in that the herbicidal composition is a mixture of methyl 1T- / 3-N'-3'-methylphenyl (carbamoyloxy) phenyl / carbamate and ethyl-N - / - ( N '-phenylcarbamoyloxy) phenyl / carbamate. - 19 - 218863 34. The method according to item 21 and 29, 'characterized in that the insecticidal agent used is a benzofuran derivative. 35. The method of item 21 and 34, characterized in that as the benzofuran derivative ^^ - dihydro ^^ - dimethyl- 7-benzofuranolmethylcarbamat verv / ends. 36 »Method according to item 21, characterized in that the solid component used is an inorganic extender. 37. Method according to item 21, characterized in that barium sulfate is used as the solid component, 38. The method according to item 21, characterized in that verv / as a solid component ketalloxyd ends. 39. The method of item 21, characterized in that verv / ends as a solid component titanium oxide. 40. The method according to item 21 to 39, characterized in that applying the polymer or polymers in a concentration on the surface of the granules, which ensures a higher concentration after the dispersion in the outer phase than the sensitisieren.de concentration, ie in Pail of polyvinyl alcohol is preferably higher. -5
in the case of polyvinylpyrrolidone, preferably higher than 10 to 10 g / l, and in the pail of methylcellulose, preferably higher than 10 to 10 g / l. 41. The method according to item 21, characterized in that the coating of the particles using a solution of polymer or of polymers in water or in an organic solvent, preferably aliphatic! 218863 Alcohol, ketone or ether or their mixture by fluidization, atomization or wetting with solvent. 42. The method according to item 21, characterized in that one prepares the solid component in the solution of the polymer. Method according to item 21, characterized in that the production of the coated particles takes place by fluidization, drying or spray-drying of the solution containing the granules of the solid component and the polymer. 44. A process for improving the buoyancy of particles dispersed in an aqueous medium, characterized in that the water-insoluble or sparingly soluble particles are coated with a water-soluble polymer or a polymer mixture before dispersion. Method according to item 44, characterized in that polyvinyl alcohol, polyvinylpyrrolidone, methylcellulose or carboxymethylcellulose-sodium or their mixture is used as the polymer. 46. The method according to item 44, characterized in that one uses the solid component or the solid components per se or previously applied to a water-insoluble support. 47. The method according to item 44, characterized in that one or more active pharmaceutical ingredients, one or more crop protection agents or an inorganic extender or a metal oxide and, if desired, pharmaceutically acceptable excipients or customary in the manufacture of pesticides additives used as the solid component. - 21 - 2t 8863 Process according to items 44 to 47, characterized in that the polymer or polymers are applied in a concentration to the surface of the granules which after dispersing in water in the external phase. a higher concentration assures than the sensitizing concentration; So in the pail of polyvinyl alcohol -5
preferably greater than 10 to 10 g / l, in the case of -5 Polyvinylpyrrolidone preferably higher than 10 to 10 g / l and in the case of methyl cellulose is preferably higher than 10 ~ ⁴ to 10 g / l. 49e The method of item 44 to 48, characterized in that the particles by atomization, fluidization or wetting with solvent using a solution of the polymer or polymers in water or in an organic solvent, preferably aliphatic alcohol, ketone or ether, or in a Mixture of the same covers. 50. The method according to item 44 to 49, characterized in that one prepares the solid component in a solution of the polymer. 51. The method according to item 44 to 49, characterized in that the preparation of the coated particles by fluidization, by drying or spray-drying of the granules of the solid component and the polymer or polymers containing solution coated. .Seiten formulas