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) at least one clay mineral, with the proviso that the weight-ratio of the clay mineral to the powderous formulation is at least 1.

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 at least one clay mineral is selected from the group consisting of Bentonite, Sepiolite Kaolinite, and Montmorillonite, preferably from Bentonite and Sepiolite as well as mixtures thereof.

4. The storage stable mixture according to claim 1, wherein the weight-ratio of the mineral clay to the powderous formulation is selected in the range of 100:1 to 1:1, 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 stable mixture according to claim 1, wherein the mixture is a premix consisting essentially of (a1) and (a2).

11. The storage stable 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 stable 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 a clay mineral 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) (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) silica, said method comprising admixing the powderous formulation with a mineral clay with the proviso that the weight-ratio of the clay mineral to the powderous formulation is at least 1.

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

A.) HPLC Method

[0117] 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.

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

[0118] 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 Inorganic Carriers

[0119] 10 g of PF-PDMN and 90 g of an inorganic 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.Math.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 inorganic carriers # Inorganic carrier Retention [%] Inv 1 Bentonite 96 Inv 2 Sepiolite 97 Ref 1 Zeolite 45 Ref 2 Diatomaceous earth (Kieselgur) 31

[0120] As can be retrieved from table 1, the use of the mineral clays according to the present invention results in an improved retention of the active compared to other inorganic carriers commonly used in the feed industry.

Example 2: Retention of PDMN in Mixtures with Different Amounts of Sepiolite.

[0121] Mixtures of PF-PDMN and different amounts of Sepiolite as outlined in Table 2 have been prepared as outlined in Example 1 (200 g batches). Then 200 g of the respective mixtures were stored in reclosed aluminium bags at 25 C. under controlled atmosphere (50% r.Math.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 2 (values above 100% are most likely due to a slight reduction in moisture content of the samples during storage).

TABLE-US-00002 TABLE 2 Retention of PDMN in a premix consisting of PF-PDMN and Sepiolite Sepiolite PF-PDMN Retention # [wt.-%] [w-%] [%] Inv 3 95 5 100 Inv 4 90 10 97 Inv 5 80 20 101 Inv 6 70 30 105 Inv 7 60 40 105

[0122] As can be retrieved, in all cases an excellent retention of PDMN was observed.

Example 3: Retention of PDMN in a Premix with Different Amounts of Sepiolite

[0123] A mineral premix consisting of vitamins (Rovimix AD3 1000/200 (0.1 wt.-%) & Rovimix E 50 Ads (1 wt.-%)), minerals (91.9 wt.-%), PF-PDMN (5 wt.-%) and soy bean oil (1 wt.-%) was admixed with various amounts of Sepiolite as illustrated in Table 3 with a TURBULA Shaker-Mixer as outlined in Example 1 (200 g batches). Then 200 g of the respective mixtures were stored in reclosed aluminium bags at 25 C. under controlled atmosphere (50% r.Math.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 3.

TABLE-US-00003 TABLE 3 Retention of PDMN in a premix Mineral Premix PF-PDMN Sepiolite Retention [wt.-%] [w-%] [wt.-%] [%] Ref 3 95 5 0 74 Inv 8 85 5 10 83 Inv 9 75 5 20 89 Inv 10 65 5 30 92 Inv 11 55 5 40 96

[0124] As can be seen the addition of Sepiolite to the mineral premix containing the powderous formulation significantly improved the retention of propandiol mononitrate.

Example 4: Retention of PDMN in a Premix Comprising Different Carriers

[0125] In a comparative trial, 80 g of a mineral premix consisting of vitamins (Rovimix AD3 1000/200 (0.1 wt.-%) & Rovimix E 50 Ads (1 wt.-%)), minerals (92.9 wt.-%) and PF-PDMN (6 wt.-%) was admixed with 20 g of either sepiolite or diatomaceous earth (Kieselgur) and then stored for 3 months in reclosed PE bags at 25 C. under controlled atmosphere (50% r.Math.H). 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 4.

TABLE-US-00004 TABLE 4 # Mineral premix Inorganic carrier Retention Inv 12 80 wt.-% Sepiolite 20 wt.-% 83% Ref 4 80 wt.-% Diatomaceous earth 66% (Kieselgur) 20 wt.-%

[0126] As can be seen the addition of Sepiolite to the mineral premix containing PF-PDMN results in a significantly better retention of PDMN compared to another inorganic carrier commonly used in the feed industry.

Example 5: Retention of PDMN in a Vitamin Premix Comprising Different Clay Minerals

[0127] 80 g of a vitamin premix consisting of vitamins (Rovimix AD3 1000/200 (0.125 wt.-%) & Rovimix E 50 Ads (2.5 wt.-%)), Bentonite (10 wt.-%), Corn Starch (20 wt.-%), Limestone (27.375 wt.-%) and PF-PDMN (20 wt.-%) were admixed with 20 g of either Sepiolite or Talc as outlined in example 1 and then stored for 3 months in reclosed PE bags at 25 C. under controlled atmosphere (50% r.Math.H). 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 4.

TABLE-US-00005 TABLE 5 Vitamin premix Clay mineral Retention Inv 13 80 wt.-% Sepiolite 20 wt.-% 91% Inv 14 80 wt.-% Talc 20 wt.-% 78%

Example 6: Retention of PDMN in a Mineral Premix Comprising Different Clay Minerals

[0128] 80 g of a mineral premix consisting of vitamins (Rovimix AD3 1000/200 (0.022 wt.-%) & Rovimix E 50 Ads (0.441 wt.-%)), minerals (50 wt.-%), Bentonite (10 w.-%) Rice hulls (16.01 wt.-%) and PF-PDMN (3.527 wt.-%) was admixed with 20 wt.-% of either Sepiolite or Talc as outlined in example 1 and then stored for 3 months in reclosed PE bags at 25 C. under controlled atmosphere (50% r.Math.H). 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 6.

TABLE-US-00006 TABLE 6 Mineral premix Clay mineral Retention Inv 15 80 wt.-% Sepiolite 20 wt.-% 97% Inv 16 80 wt.-% Talc 20 wt.-% 77%