STORAGE STABLE MIXTURES

Abstract

The present invention relates to improved formulations of propandiol mononitrate and derivatives thereof as well as to the production of such formulations.

Claims

1. A storage stable mixture comprising (a1) a powderous formulation comprising (i) 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.6alkyl, 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.6alkyl, phenyl, pyridyl such as preferably 2-pyridyl with the proviso that when n is >3 the hydrocarbon chain may be interrupted by O or NH, and (ii) silica, and (a2) native starch.

2. The storage stable mixture according to claim 1, wherein the compound according to formula (I) is propandiol mononitrate.

3. The storage stable mixture according to claim 1, wherein the native starch is derived from potatoes, wheat, maize, rice, and/or cassava.

4. The storage stable mixture according to claim 1, wherein the weight-ratio (w/w) of the starch to the powderous formulation is selected in the range of 50:1 to 1:5, preferably in the range of 40:1 to 1:2, most preferably in the range of 30:1 to 1:1 or 20:1 to 1:1.

5. The storage stable mixture according to claim 1, wherein the powderous formulation consists essentially of (i) 2 to 20 wt-%, based on the total weight of the powderous formulation, of a compound of formula (I), and (iii) at least 25 wt-%, based on the total weight of the powderous formulation, of silica, and (iv) 10 wt-% to 45 wt-%, based on the total weight of the powderous formulation, of an edible oil, and (v) 0 to 10 wt-%, based on the total weight of the powderous formulation, of an additive.

6. The storage stable mixture according to claim 5, wherein the edible oil in the powderous formulation is selected from the group consisting of propyleneglycol, canola oil, corn oil, rapeseed oil, sunflower oil, middle chain triglyceride (MCT) and glycerol as well as mixtures thereof.

7. The storage stable mixture according to claim 5, wherein the additive is a thickener selected from the group consisting of gums and/or cellulose derivatives, preferably from xanthan gum, karaya gum and/or ethylcellulose.

8. The storage stable mixture according to claim 5, wherein the edible oil is propyleneglycol.

9. The storage stable mixture according to claim 1, wherein the powderous formulation consists essentially of (i) 2 to 15 wt-%, based on the total weight of the powderous formulation, of propandiol mononitrate, and (ii) at least 45 wt-%, based on the total weight of the powderous formulation, of silica, and (iii) 20 to 40 wt-%, based on the total weight of the powderous formulation, of propyleneglycol.

10. The storage mixture according to claim 1, wherein the mixture is a premix consisting essentially of (a1) and (a2).

11. The storage mixture according to claim 1, wherein the mixture is a premix further comprising (a3) at least one active ingredient selected from the group of water-soluble and/or fat-soluble vitamins, trace and/or macro minerals, amino acids as well as mixtures thereof, and optionally (a4) at least one edible oil, with the proviso that the amount of ingredients (a1) to (a4) sum up to 100 wt.-%.

12. The storage mixture according to claim 1, wherein the mixture is a feed product further comprising (a3/1) at least one active ingredient selected from the group consisting of water-soluble and/or fat-soluble vitamins, trace and/or macro minerals, amino acids as well as mixtures thereof and (a3/2 at least one feed ingredient selected from the group of roughage and concentrates, and optionally (a4) at least one edible oil.

13. Use of native starch to enhance the retention of a compound of formula (I) ##STR00003## 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.6alkyl, 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.6alkyl, phenyl, pyridyl such as preferably 2-pyridyl with the proviso that when n is >3 the hydrocarbon chain may be interrupted by O or NH in a powderous formulation comprising (i) the compound according to formula (I), and (ii) silica.

14. A method of improving the retention of a compound of formula (I) ##STR00004## 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.6alkyl, 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.6alkyl, phenyl, pyridyl such as preferably 2-pyridyl with the proviso that when n is >3 the hydrocarbon chain may be interrupted by O or NH in a powderous formulation comprising (i) the compound according to formula (I), and (ii) (ii) silica, said method comprising admixing the powderous formulation with native starch.

15. Use according to claim 13, wherein the retention after at least 4 weeks is at least 80%, preferably at least 85% most preferably at least 90% such as in particular at least 95%.

Description

EXAMPLES

General Information

[0126] A.) HPLC Method

[0127] 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.

[0128] B.) Powderous Formulation Comprising Propandiol Mononitrate (PF-PDMN)

[0129] To 80 g of silica (Newsil C50) placed on a beaker, are added 80 g of a 20 wt.-% propandiol mononitrate (PDMN) solution in propyleneglycol under gentle agitation at room temperature. After 5 minutes agitation, the adsorption is completed and a free-flowing powder is obtained.

Example 1: Retention of PDMN in PF-PDMN Admixed with Different Carriers

[0130] 10 g of PF-PDMN and 90 g of an organic carrier as outlined in table 1 have been mixed with a TURBULA Shaker-Mixer (64 rotations/min) for 10 min, sieved through a 2 mm sieve and mixed again for 10 min to obtain homogenous mixtures (100 g batches). Then 10 g of the respective mixtures were stored in reclosed PE bags at 25 C. under controlled atmosphere (50% r.H) for 1 month. Afterwards the remaining content of PDMN was determined by HPLC. The results (as relative concentration to the initial value set to 100%) are presented Table 1.

TABLE-US-00001 TABLE 1 Retention of PDMN in PF-PDMN in dependence of various organic carriers # Organic carrier Retention [%] Inv 1 Maize starch 93 Ref 1 Rice Hulls 89 Ref 2 Modified starch* 48 *starch sodium octenyl succinate (OSA-starch).

[0131] As can be retrieved from table 1, the use of the starch according to the present invention resulted in an improved retention of the active compared to other organic carriers commonly used in the feed industry.

Example 2: Retention of PDMN in PF-PDMN Admixed with Different Carriers

[0132] 11 g of PF-PDMN and 11 g of the respective starch/starch derivative as outlined in table 2 have been mixed with a TURBULA Shaker-Mixer (64 rotations/min) for 10 min, sieved through a 2 mm sieve and mixed again for 10 min to obtain homogenous mixtures (22 g batches). Then two samples (5 g each) of the respective mixtures were stored in reclosed PE bags at 40 C. under controlled atmosphere (75% r.H) for 1 week. Afterwards the remaining content of PDMN was determined by HPLC. The results (as relative concentration to the initial value set to 100%) are presented Table 2.

TABLE-US-00002 TABLE 2 Retention of PDMN in PF-PDMN admixed with different starch types in a 1:1 ratio # Organic carrier Retention [%] Inv 2 Maize starch 92 Ref 3 Modified starch* 88 *starch sodium octenyl succinate (OSA-starch). As can be retrieved from table 2, also at lower starch ratios the use of native starch resulted in an improved retention of the active compared to the use of modified (OSA) starch, even under stress conditions (i.e. high temperature and high humidity).