DD270900A1 - NEW UREASE INHIBITER POLYMER COMBINATIONS - Google Patents

Abstract

The invention relates to novel urease inhibitor-polymer combinations consisting of a low molecular weight urease inhibitor and a synthetic or natural polymer matrix as Traeger. The aim of the invention is to protect and release delayed by combining PPDA with synthetic and natural polymers while maintaining the biological activity of the low molecular weight urease inhibitor from environmental influences and rapid biological and / or hydrolytic degradation. According to the invention, this object is achieved by adding the urease inhibitor, preferably PPDA, to a solution of the polymer and casting films, films or moldings from the dissolved or suspended state and then granulating them, or by precipitation PPDA-containing polymer granules are obtained directly , The active ingredient-containing granules can additionally be enveloped with a polymer layer in order to achieve an extension of the active ingredient release. The content of PPDA may be between 5 to 90% by mass and the average particle diameter may be 0.05 to 5 mm.

Description

Title of the invention New urease inhibitor polymer combinations Field of application of the invention

The invention relates to urease-inhibiting combinations consisting of a low molecular weight urease inhibitor and a synthetic or natural polymer matrix as a carrier. The inhibition of urease mioht sioh especially when using urea in agricultural fertilization and in animal nutrition required to delay the enzymatisohen urea degradation and thus to avoid N-losses and harmful Neb'enwirkungen by the cleavage products.

Characteristics of the known state of Teohnik

A number of low molecular weight urease inhibitors are known; among which the Phosphorsäurephenylesterdiamid (PPDA) is particularly effective (see H.-M. Miohel: The Pharmacy 21 (1980) 63). Their application takes the form of powders, solutions, suspensions or emulsions. As a result of flushing or degradation duroh environmental influences or microorganisms arise-high losses, which high or repeated drug inputs are necessary, which are associated with a considerable economic outlay. It is known that to eliminate these Naohteile the drug PPDA ohemisoh can be fixed in polymer chains (DD-WP 159004). The essential Naohteil these polymeric Ureaseinhibitoren is the high cost of their production. In addition to these complex synthetic work usually additional Verfahrenssohritte necessary to bring the polymer-drug combinations in a corresponding application form.

Object of the invention

The aim of the invention is to protect and delay the release of the biological activity of the low molecular weight urease inhibitor by combining PPDA with synthetic and natural polymers to protect it against environmental influences and rapid biological and / or hydrolytic degradation.

Explanation of the essence of the invention

According to the invention this object is achieved daduroh that the Ureaseinhibitor, preferably PPDA, is added to a solution of the polymer and cast from the dissolved or suspended Zuetand films, films or moldings and then granulated, or that duroh failures PPDA-containing PolymergranuäjLte be obtained directly , The active ingredient-containing granules can additionally be coated with a polymer alcohol to achieve an extension of the active ingredient release. The coating m.'x the film-forming polymer can Naoh the known method of fluidized bed or in a simple manner duroh mixing the active ingredient-containing granules with a 0.5 to 5% solution or dispersion of the film-forming polymer with simultaneous evaporation of the solvent. The average partial diameter may be varied within the limits of 0.05 to 5 mm, preferably 0.08 to 0.5 mm, and the content of PPDA may be varied from 5 to 90 % by mass.

As polymers are used:

Polyvinyl alcohol, polyvinyl acetate, copolymers of vinyl alcohol and vinyl acetate with a vinyl acetate content of 1 to 99 mol %, alternating copolymers of maleic anhydride (MSA) with styrene, vinyl acetate, alkyl vinyl ether or 1-olefins, such as ethene, propene or isobutene and mixtures of the polymers listed above and copolymers, furthermore cellulose and cellulose derivatives, in particular carboxymethyl cellulose and salts thereof.

The choice of the polymer matrix riohto so close to the Eineatz the combination and can hinsiohtlioh with the listed polymers and copolymers or their Misohungenhs. the water solubility can be varied depending on the pH of the surrounding medium. Cellulosic acetate is preferably used as the film-forming substance for the coating of the carrier active ingredient particles. Dooh can be used in other polymeric substances, e.g. Cellulose nitrate, polyvinyl alcohol, polyvinyl acetate, copolymers of vinyl acetate and vinyl alcohol and copolymers of maleic anhydride and styrene.

The following examples illustrate the invention without limiting it.

A'usführungsbei games Example 1:

1 g maleic anhydride / Vinylaoetat copolymer and 1.2 g FPDA are dissolved in 5 ml Aoeton and the solution poured into a Petri dish where SiOH forms duroh evaporation of Aoetons at room temperature for a 5k mass% PPDA containing opaque, brittle film that Nooh 2 h dried in vacuo and then granulated. In the soil test, these granules, in addition to other similar combinations of MSA copolymers, show a similar effect to PPDA. The results are summarized in Table 1 (Sample Nos. 1 to 3).

Example 2:

1 g of a vinyl alcohol / vinyl acetate copolymer having a vinyl acetate content of 31 mol % and 0.5 g of PPDA are dissolved in aoeton and a film prepared as in Example 1 and then granulated. The monolithic combination contains 37.7 % by weight of PPDA and is effective as a ureease inhibitor (Sample No. k in Table 1).

Example 3:

The samples prepared in Example 1 are thermostated in bidistilled water at 30 ° C. and the concentration of the active ingredient released from the PPDA-polymer combinations is monitored over time. The concentration-time profile is shown for samples Nos. 1 and 2 in Figure 1, where the comparison shows the hydrolytic degradation of the pure PPDA. From Figure 1 it can be seen that by combining PPDA with a polymer over an extended period of time, an effective PPDA concentration due to controlled release from the polymer can be adjusted.

Example 4:

5 g of sodium carboxymethyloellulose and 1.5 g of PPDA are dissolved in 50 ml of water and the polymer is precipitated by dropwise addition to a solution of calcium chloride, water and ethanol (7: 3: 2) and filtered off with suction in vacuo over P 2 O 3 getrooknet. The calcium oxymethyloellulose granules thus prepared contain 14.3 mass % PPDA and have a better urease inhibiting action in the soil after 9 days than PPDA alone (Sample No. 5 in Table 2).

Example 5:

3 g of Caloiumoarboxymethyloellulose-PPDA granules shown in Example 4 are impregnated with 15 ml of a 5 7 * igen solution of cellulose triacetate in dichloromethane and the solvent removed in a stream of air. The coated granules contain 13.2 % by weight of PPDA and have a comparable dom PPDA (Sample No. 6 in Table 2).

Example 6:

The PPDA polymer granules prepared in Examples 4 and 5 are subjected, as in Example 3, to release studies. From Figure 2 it can be seen that by means of the delayed release of PPDA from the caliumooxymethylcellulose granules, the urease-inhibiting PPDA concentration can be kept almost constant over a period of 80-300 hours. Duroh enveloping the PPDA-containing Calciumoarboxymethyloellulose with cellulose acetate can eioh further delay the drug release and adjust over a longer period of time a constant urease-inhibiting PPDA concentration, but at a lower level.

Example 7:

5 g Natriumoarboxymethyloellulose and 1.2 g of PPDA are dissolved in 50 ml of water and the polymer by dropwise addition of the aqueous solution in 300 ml of THF ausgeftU.lt and NaOH the filtered under vacuum over P ^ O ^ Q dried. The PPDA-containing sodium oxyoxymethyloellulose granules thus obtained are impregnated with 25 ml of a 5% solution of cellulose triacetate in dioctomethane and the solvent removed in a stream of air. The coated granules contain 12.0 % by weight of PPDA and show an effect comparable to PPDA (Sample No. 7 in Table 2).

Example 8:

5 g Perloellulose be suspended in 50 ml of a 2 Äigen solution of PPDA in Aoeton, decanted off the excess solution and the solvent removed from the residue in the air stream. The granules contain 6.8 % by weight of PPDA and show a potential for pure PPDA (Sample No. 8 in Table 2).

Table 1: Urea Assay of Harnetof PPDA / Polymer Gemisohen in the Soil (Effective Efficiency 1 %)

Rehearse- copolymer PPDA share inhibition the NH ₃ -N- No. in % losses in % naoh meet 3. 5. 7th 10th PPDA 100 97 92 60 29 1. Maleic anhydride / styrene 70.5 97 82 39 ?8th Second Malic acid anhydride / vinyl acetate 54.1 97 85 45 28 Third Maleic anhydride / propene 73.8 98 86 45 24 4th Vinyl alcohol / vinyl acetate 37.7 58 24 19

Table 2: Urea-Utilization of Urea «PPDA / Polymer-Gemisohen in the soil (drug expenditure staggered)

Sample no.

Drug expenditure in %.

PPDA share in %

Inhibition of NH ~ -N losses in % of days

4th

7th

9th

PPDA

0.5 1.0 2.0

0.5 1.0 2.0

0.5 1.0 2.0

0.5 1.0 2.0

0.5 1.0 2.0

100 94 31 9 100 97 32 8th 100 97 44 12 14.3 97 40 21 14.3 90 31 12 14.3 92 31 11 13.2 91 25 7 13.2 94 31 9 13.2 96 35 14 12.0 92 · 33 9 12.0 93 34 21 12.0 93 39 15 6.8 96 23 5 6.8 92 23 3 6.8 97 33 8th

Claims (5)

273) 9 OO S claim 1. New urease inhibitor-polymer combinations, characterized in that the urease inhibitor, preferably PPDA, is embedded in a solid polymer matrix and the polymer protects the urease inhibitor from environmental influences and rapid biological and / or hydrolytic degradation and only after application on receipt of the bio-logical effect is released delayed. ι 2. New urease inhibitor-polymer combinations of Aiispruoh 1, characterized in that the PPDA-containing polyser granules are coated, using as encapsulating polymer. , cellulose acetate, cellulose nitrate, polyvinyl alcohol, polyvinyl acetate, copolymers of vinyl acetate and vinyl alcohol, such as copolymers of maleic anhydride and styrene. 3. New Ureaseinhibitor polymer combinations Anspruoh 1 and 2, characterized daduroh that as a polymeric matrix polyvinyl alcohol, polyvinyl acetate, copolymers of vinyl alcohol and vinyl acetate having a Vinylaoetatgehalt 1-99% by weight , copolymers of maleic anhydride with styrene, vinyl acetate, alkyl vinyl ether or 1-olefins, such as ethene, propene or isobutene, cellulose and cellulose derivatives, in particular carboxymethylcellulose and salts thereof, and mixtures of the polymers and copolymers listed above are used. 4. New urease inhibitor polymer combinations according to the claims 1, 2 and 3, characterized in that it contains 5 to 90 % by mass of urease inhibitor :. 5. New urea inhibitor-polymer combinations Na Anapruoh 1, 2, 3 and Λ, characterized daduroh that their Teilohengrößen 0.05 to 5 mm, preferably 0.08 to 0.5 mm.