Storage-stable formulations

Abstract

The present invention relates to storage-stable formulations of 3-nitrooxypropanol and derivatives thereof as well as to the production of such formulations.

Claims

1. A storage-stable powderous formulation comprising: (i) at least 0.1 weight-% (wt-%), based on the total weight of the powderous formulation, of a compound of formula (I): ##STR00002## wherein n is an integer from 1 to 15; R.sup.1 is selected from the group consisting of H, C.sub.1-C.sub.6 alkyl, phenyl, OH, NH.sub.2, CN, COOH, O(CO)R.sup.8, NHC(O)R.sup.8, SO.sub.2NHR.sup.8, and ONO.sub.2, and R.sup.8 is C.sub.1-C.sub.6 alkyl, phenyl or pyridyl; with the proviso that when n is >3 the hydrocarbon chain may be interrupted by O or NH; (ii) 0 to 40 wt-%, based on the total weight of the powderous formulation, of an edible oil, and (iii) at least 25 wt-%, based on the total weight of the powderous formulation, of silica having a particle size D(v, 0.5) of 320 m.

2. The storage-stable powderous formulation according to claim 1 which further comprises: (iv) 0 to 10 wt-%, based on the total weight of the powderous formulation, of water and/or an additive.

3. The storage-stable powderous formulation according to claim 2, wherein the additive is a thickener selected from the group consisting of gums and/or cellulose derivatives.

4. The storage-stable powderous formulation according to claim 3, wherein the additive is a thickener selected from the group consisting of xanthan gum, karaya gum and/or ethylcellulose.

5. The storage-stable powderous formulation according to claim 1 consisting of (i) 2 to 20 wt-%, based on the total weight of the powderous formulation, of the compound of formula (I), (ii) 10 wt-% to 45 wt-%, based on the total weight of the powderous formulation, of the edible oil, (iii) at least 35 wt-%, based on the total weight of the powderous formulation, of the silica having a D(v, 0.5) of 320 m, and (iv) 0 to 10 wt-%, based on the total weight of the powderous formulation, of water and/or an additive.

6. The storage-stable powderous formulation according to claim 1, wherein n is an integer between 3 and 9 and R.sup.1 is OH, COOH or ONO.sub.2.

7. The storage-stable powderous formulation according to claim 1, wherein the compound of formula (I) is selected from the group consisting of 3-nitrooxypropanol, 9-nitrooxynonanol, 5-nitrooxy pentanoic acid, 6-nitrooxy hexanoic acid, bis(2-hydroxyethyl)amine dinitrate, 1,4-bis-nitrooxybutane and 1,5-bis-nitrooxypentane.

8. The storage-stable powderous formulation according to claim 1, wherein the edible oil is selected from the group consisting of propyleneglycol, corn oil, rapeseed oil, sunflower oil, middle chain triglyceride (MCT), glycerol and mixtures thereof.

9. The storage-stable powderous formulation according to claim 1, wherein the edible oil is propyleneglycol.

10. The storage-stable powderous formulation according to claim 1 consisting of: (i) 2 to 12 wt-%, based on the total weight of the powderous formulation, of 3-nitrooxypropanol, (ii) 20 to 40 wt-%, based on the total weight of the powderous formulation, of propyleneglycol, (iii) at least 40 wt-%, based on the total weight of the powderous formulation, of the silica having a particle size D(v, 0.5) of 320 m, and (iv) 0 to 7 wt-%, based on the total weight of the powderous formulation, of water.

11. The storage-stable powderous formulation according to claim 1, wherein the particle size D(v, 0.5) of the silica is a range of 100 to 320 m.

12. The storage-stable powderous formulation according to claim 1, wherein the particle size D(v, 0.5) of the silica is a range of 200 to 300 m.

13. The storage-stable powderous formulation according to claim 1, wherein the silica exhibits a pH in a range of 6 to 7.

14. The storage-stable powderous formulation according to claim 1, wherein the formulation contains a coating which is selected from the group consisting of glycerine monostearate, carnauba wax, candelilla wax, sugarcane wax, palmitic acid, stearic acid hydrogenated cottonseed oil, hydrogenated palm oil, hydrogenated rapeseed oil and mixtures thereof.

15. The storage-stable powderous formulation according to claim 1, wherein the formulation exhibits retention of the compound of formula (I) which is at least 80%.

16. The storage-stable powderous formulation according to claim 1, wherein R.sup.8 is 2-pyridyl.

17. The storage-stable powderous formulation according to claim 1, wherein the particle size D(v, 0.5) of the silica is in a range of 200 to 310 m.

18. The storage-stable powderous formulation according to claim 1, wherein the formulation exhibits a retention of the compound of formula (I) which is at least 85%.

19. The storage-stable powderous formulation according to claim 1, wherein the formulation exhibits a retention of the compound of formula (I) which is at least 87%.

20. A feed product which comprises the storage-stable formulation according to claim 1.

Description

EXAMPLES

(1) Particle Size Determination:

(2) The methodology described below followed the recommendations outlined in IS013320-1 for diffraction light scattering techniques.

(3) The particle sizes of various silica grades have been measured by a Malvern Master Sizer 2000 following the recommendation of ISO13320-1 for diffraction light scattering techniques. An aliquot of about 5 grams of the material tempered at 25 C.-35 to 55% r.H is sampled into the vibrator hopper of the dry dispersion unit (Sirocco). The flow aperture of the dispenser gate is set up on the way that the product flows for 30 seconds through the measurement zone using a tygon tube, at a vibration feed rate of 50%. A sample measurement at 0.1 bar of disperser pressure is taken for 30 seconds and a snap of 30000. The sample pass through the focused beams of light (Helium-neon laser for the red light and solid state light source for the blue) and scatter the light allowing a measurement of particles between 0.02 and 2000 micrometers. The medium particle diameter in volume, D(v, 50), is determined using Fraunhofer approximation.

(4) pH Determination of the Silica:

(5) a solution or suspension of distillated water with 1% of the respective silica is prepared. After 5 minutes the solution or suspension is stirred magnetically and measured at room temperature with a standard pH-electrode.

(6) Preparation of the Formulation:

(7) To 80 g of different type of silica grades as outlined in table 1) placed on a beaker, is added 80 g of a 20 wt.-% 3-nitrooxypropanol solution in propyleneglycol under gentle agitation at room temperature. After 5 minutes agitation, the adsorption is completed and a free flowing powder is obtained.

(8) Stability Study:

(9) Two aluminium bags containing 5 g of the respective formulation are stored open at 25 C. under controlled atmosphere (50% r.H). The concentration of 3-nitrooxypropanol was determined by HPLC using an Agilent High Performance Liquid Chromatography 1260 Infinity system, using an Aquasil C18, 1503 mm, 3 m column and detecting at 210 nm. The column oven was set to 23 C., the autosampler not temperature controlled. The mobile phase consisted of mobile phase A (940 mL Milli-Q-water+60 ml acetonitrile+1 mL methane sulfonic acid) and mobile phase B (800 ml Milli-Q-water+200 ml acetonitrile+1 mL methane sulfonic acid) which were used in gradient mode (0 min: 0% B, 15 min: 0% B, 15.5 min: 100% B, 21 min: 100% B, 21.5 min: 0% B, 25 min: 0% B (=end of run)) with a flow of 0.4 ml/min. The results (as relative concentration to the initial value set to 100%) are presented Table 1.

(10) TABLE-US-00001 TABLE 1 Silica Particle size Retention [D(v, 0.5) in m] pH initial 12 weeks 296 6.6 100 88 285 7.9 100 87 224 7.0 100 89 339 (Reference) 7.5 100 77

(11) As can be retrieved from table 1, the use of the specific silica according to the present invention results in an improved retention of the active.