SUNFLOWER PHOSPHOLIPID COMPOSITION CONTAINING PHOSPHATIDYLCHOLINE

Abstract

The present invention relates to sunflower phospholipid compositions containing phosphatidylcholine and containing less than 0.1% by weight, in particular less than 0.08% by weight or less than 0.05% by weight and especially less than 0.02% by weight of chlorogenic acids, based on the total weight of the sunflower phospholipid composition, and combination thereof with at least one anionic stabilizer compound comprising at least one anionic phospholipid compound. These combinations are particularly useful as emulsifiers in aqueous oil-in-water emulsions. The present invention also relates to aqueous oil-in-water emulsions containing such combinations of a sunflower phospholipid composition with at least one anionic stabilizer compound comprising at least one anionic phospholipid compound. The invention also relates to a method for the production of such emulsions. The present invention relates in particular to sunflower phospholipid compositions containing an amount of phosphatidylcholine of 45% by weight or higher and having a low content of chlorogenic acids of less than 0.1% by weight and at least one anionic phospholipid compound.

Claims

1. The use of a sunflower phospholipid composition containing phosphatidylcholine and containing less than 0.1% by weight of chlorogenic acids, based on the total weight of the sunflower phospholipid composition, in combination with at least one anionic stabilizer compound comprising at least one anionic phospholipid compound as an emulsifier in an aqueous oil-in-water emulsion for parenteral administration.

2. The use of claim 1, where the sunflower phospholipid composition contains at least one anionic phospholipid compound in addition to the phosphatidylcholine.

3. The use of any one of claim 1 or 2, where the anionic phospholipid compound is selected from the group consisting of phosphatidylglycerol, phosphatidylinositol, PEGylated phosphatidylethanolamine, phosphatidylserine, phosphatidic acid, 1,3-bis(sn-3′-phosphatidyl)-sn-glycerol and combinations thereof.

4. The use of claim 3, where the anionic phospholipid compound is phosphatidylglycerol, in particular 1,2-dimyristoyl-sn-glycero-3-phosphorylglycerol.

5. The use of any one of claims 1 to 4, where the weight ratio of the anionic phospholipid compound and sunflower phospholipid composition is in the range of 0.2:99.8 to 20:80.

6. The use of any one of the preceding claims, where the sunflower phospholipid composition contains phosphatidylethanolamine.

7. The use of any one of the preceding claims, where the sunflower phospholipid composition contains phosphatidylcholine in an amount of at least 45% by weight, based on the total weight of the phospholipid composition.

8. The use of any one of the preceding claims, where the sunflower phospholipid composition is used in such an amount that the concentration of phosphatidylcholine in the oil-in-water emulsion is in the range of 0.1 to 20% by weight, based on the total weight of the water-in-oil emulsion.

9. The use of any one of the preceding claims, where the oil-in-water emulsion for parenteral administration is an oil-in-water emulsion for parenteral nutrition.

10. A combination of a sunflower phospholipid composition containing phosphatidylcholine in an amount of at least 45% by weight, based on the total weight of the sunflower phospholipid composition and having a content of chlorogenic acids of less than 0.1% by weight, based on the total weight of the sunflower phospholipid composition, with at least one anionic stabilizer compound comprising at least one anionic phospholipid compound.

11. A sunflower phospholipid composition containing phosphatidylcholine in an amount of at least 45% by weight, based on the total weight of the sunflower phospholipid composition, and at least one anionic stabilizer compound comprising at least one anionic phospholipid compound and having a content of chlorogenic acids of less than 0.1% by weight, based on the total weight of the sunflower phospholipid composition.

12. The combination of claim 10 or the composition of claim 11, where the anionic phospholipid compound is selected from the group consisting of phosphatidylglycerol, phosphatidylinositol, PEGylated phosphatidylethanolamine, phosphatidylserine, phosphatidic acid, 1,3-bis(sn-3′-phosphatidyl)-sn-glycerol and combinations thereof.

13. The combination or composition of claim 12, where the anionic phospholipid compound is phosphatidylglycerol, in particular 1,2-dimyristoyl-sn-glycero-3-phosphorylglycerol.

14. The combination or composition of any one of claims 10 to 13, where the weight ratio of the anionic phospholipid compound and phosphatidylcholine is in the range of 0.2:99.8 to 30:70.

15. An aqueous oil-in-water emulsion for parenteral administration, in particular for parenteral nutrition which contains a) an oil phase comprising a triglyceride composition suitable for parenteral administration, in particular for parenteral nutrition, b) a combination of the sunflower phospholipid composition containing less than 0.1% by weight of chlorogenic acids, based on the total weight of the sunflower phospholipid composition, with at least one anionic stabilizer compound comprising at least one phospholipid compound, as defined in any one of claims 1 to 10,  or the sunflower phospholipid composition of any one of claims 11 to 14, and c) water.

16. The aqueous oil-in-water emulsion of claim 15, where the oil phase essentially consists of a triglyceride composition suitable for parenteral administration.

17. The aqueous oil-in-water emulsion of any one of claim 15 or 16, where the anionic phospholipid compound is selected from the group consisting of phosphatidylglycerol, phosphatidylinositol, PEGylated phosphatidylethanolamine, phosphatidylserine, phosphatidic acid, 1,3-bis(sn-3′-phosphatidyl)-sn-glycerol and combinations thereof.

18. The aqueous oil-in-water emulsion of any one of claims 15 to 17, where the weight ratio of the anionic phospholipid compound and phosphatidylcholine is in the range of 0.2:99.8 to 15:85.

19. The aqueous oil-in-water emulsion of any one of claims 15 to 18, which contains a) 5 to 35 by weight%, based on the total weight of the aqueous oil-in-water emulsion, of the oil phase, b) the combination of the sunflower phospholipid composition containing less than 0.1% by weight of chlorogenic acids, based on the total weight of the sunflower phospholipid composition, with at least one anionic phospholipid compound, as defined in any one of claims 1 to 10,  or the sunflower phospholipid composition of any one of claims 11 to 14, where the amount of the sunflower composition is such that the concentration of phosphatidylcholine in the oil-in-water emulsion is in the range of 0.1 to 20% by weight, based on the total weight of the oil-in-water emulsion, and c) water.

20. The aqueous oil-in-water emulsion of any one of claims 15 to 19, which contains less than 100 ppm of chlorogenic acids.

21. The aqueous oil-in-water emulsion of any one of claims 15 to 20, which has a pH value in the range of pH 4 to pH 10, as determined at 20° C. and 1 bar.

22. A process for preparing an aqueous oil-in-water emulsion for parenteral administration as claimed in any one of claims 15 to 21 comprising i. Providing an aqueous phase and an oil phase; ii. Emulsifying the oil phase in the aqueous phase in the presence of the combination of the sunflower phospholipid composition containing less than 0.1% by weight of chlorogenic acids, based on the total weight of the sunflower phospholipid composition, with at least one anionic stabilizer compound comprising an anionic phospholipid compound, as defined in any one of claims 1 to 10 or in the presence of the sunflower phospholipid composition of any one of claims 11 to 14; iii. Homogenizing the emulsion obtained in step to a droplet size suitable for parenteral administration.

23. The process of claim 22, which further comprises mixing the sunflower phospholipid composition containing phosphatidylcholine with one or more anionic phospholipids prior to dispersing the mixture in water.

24. The process of any one of claim 22 or 23, which further comprises sterilizing the homogenized emulsion of step iii. by autoclaving.

25. An oil-in-water emulsion for parenteral administration which is obtainable by a method of any one of claims 22 to 24.

26. A process for producing a sunflower phospholipid composition of any one of claims 11 to 14, which comprises the following steps: i) extracting a sunflower lecithin with a solvent selected from acetone and mixtures thereof with water, to obtain an extract and a residue, followed by ii) repeated extraction of the residue with ethanol or a mixture thereof with water to obtain ethanolic extracts, iii) combining the ethanolic extracts and removing the ethanol and optional water to obtain sunflower phospholipid composition containing phosphatidylcholine in an amount of at least 45% by weight, based on the total weight of the sunflower phospholipid composition, and having a content of chlorogenic acids of less than 0.1% by weight, based on the total weight of the sunflower phospholipid composition, iv) dissolving the sunflower phospholipid composition obtained in step iii) and at least one further anionic phospholipid compound in an organic solvent and evaporating the solvent.

Description

PREPARATION EXAMPLES

[0172] In the following preparation examples glycerol was used as a tonicity agent in an amount of 2.25% by weight. In each example, the amount of water was chosen such that the batch size was 500 g.

Example 1 (Not According to the Invention)

[0173] Glycerol and water for injection were mixed. Phospholipid composition P1 (6.0 g) was added and the mixture was stirred at 50° C., until the phospholipid was completely dispersed. Purified soybean oil (100 g) was heated separately to 60° C. The aqueous phase was mixed with a high-shear mixer at 10.000 rpm. Mixing was continued while the heated oil phase was added slowly. pH was adjusted to 8.5 by adding a sodium hydroxide solution in water (0.5M). The resulting pre-emulsion was then homogenized using a high-pressure homogenizer in five passes at a pressure of 800 bar. Temperature was kept at 50° C. to 70° C. during homogenization. Prior to the 5.sup.th pass, pH was again adjusted to 8.5. After the homogenization, the emulsion was cooled below 30° C., filled in glass vials and autoclaved.

[0174] Analytical data:

[0175] Homogenous, white liquid

[0176] pH value: 7.4

[0177] Average particle size (PdI): 229 nm (0.046)

[0178] Stability: Free fat visible after 3 months storage at RT

Example 2

[0179] Glycerol and water for injection were mixed. Phospholipid composition P1 (6.0 g) and DMPG-Na (0.30 g) were added and the mixture was stirred at 50° C., until the phospholipids were completely dispersed. Purified soybean oil (100 g) was heated separately to 60° C. The aqueous phase was mixed with a high-shear mixer at 10.000 rpm. Mixing was continued while the heated oil phase was added slowly. pH was adjusted to 7.5 by adding a sodium hydroxide solution in water (0.5M). The resulting pre-emulsion was then homogenized using a high-pressure homogenizer in five passes at a pressure of 800 bar. Temperature was kept at 50° C. to 70° C. during homogenization. Prior to the 5.sup.th pass, pH was again adjusted to 7.5. After the homogenization, the emulsion was cooled below 30° C., filled in glass vials and autoclaved.

[0180] Analytical data:

[0181] Homogenous, white liquid

[0182] pH value: 6.8

[0183] Average particle size (PdI): 220 nm (0.099)

[0184] Stability: 3 m at 45° C.:

[0185] Homogenous, white liquid

[0186] pH value: 6.5

[0187] Average particle size: 234 nm

[0188] 6 m at room temperature:

[0189] Homogenous, white liquid

[0190] pH value: 7.7

[0191] Average particle size: 234 nm

[0192] 18 m at room temperature:

[0193] Homogenous, white liquid

[0194] pH value: 7.6

[0195] Average particle size: 238 nm

Example 3

[0196] Glycerol and water for injection were mixed. The phospholipid composition P5 (6.0 g) was added and the mixture was stirred at 50° C., until the phospholipids were completely dispersed. Purified soybean oil (100 g) was heated separately to 60° C. The aqueous phase was mixed with a high-shear mixer at 10.000 rpm. Mixing was continued while the heated oil phase was added slowly. pH was adjusted to 8.3 by adding a sodium hydroxide solution in water (0.5M). The resulting pre-emulsion was then homogenized using a high-pressure homogenizer in five passes at a pressure of 800 bar. Temperature was kept at 50° C. to 70° C. during homogenization. Prior to the 5.sup.th pass, pH was again adjusted to 8.5. After the homogenization, the emulsion was cooled below 30° C., filled in glass vials and autoclaved.

[0197] Analytical data:

[0198] Homogenous, white liquid

[0199] pH value: 7.7

[0200] Average particle size (PdI): 245 nm (0.070)

[0201] Stability: 6 w at 45° C.:

[0202] Homogenous, white liquid

[0203] pH value: 7.9

[0204] Average particle size: 239 nm

[0205] 3 m at 45° C.:

[0206] Homogenous, white liquid

[0207] pH value: 7.9

[0208] Average particle size: 241 nm

[0209] 12 m at room temperature:

[0210] Homogenous, white liquid

[0211] pH value: 7.9

[0212] Average particle size: 241 nm

Example 4

[0213] Example 4 was carried out according to the protocol of example 1 using phospholipid composition P3 (6.0 g) instead of phospholipid composition P1 (6.0 g).

[0214] Analytical data:

[0215] Homogenous, white liquid

[0216] pH value: 7.7

[0217] Average particle size (PdI): 242 nm (0.095)

[0218] Stability: 3 m at 45° C.:

[0219] Homogenous, white liquid

[0220] pH value: 7.6

[0221] Average particle size: 250 nm 12 m at room temperature:

[0222] Homogenous, white liquid

[0223] pH value: 7.6

[0224] Average particle size: 260 nm

Example 5 (Not According to the Invention)

[0225] Example 5 was carried out according to the protocol of example 1 using phospholipid composition P2 (6.0 g) instead of phospholipid composition P1 (6.0 g). After first pH adjustment, the pre-emulsion turned green. After autoclaving, the green color had faded and the emulsion had an off-white color.

[0226] Analytical data:

[0227] Homogenous, off-white liquid

[0228] pH value: 7.6

[0229] Average particle size (PdI): 253 nm (0.094)

[0230] Stability: 6 w at 45° C.:

[0231] Off-white liquid with small oil droplets on the surface

[0232] pH value: 7.0

[0233] Average particle size: 239 nm

[0234] 3 m at 45° C.:

[0235] Off-white liquid with free fat on the surface

[0236] pH value: 6.9

[0237] Average particle size: n.d.

[0238] 12 m at room temperature:

[0239] Off-white liquid with small oil droplets on the surface

[0240] pH value: 7.2

[0241] Average particle size: 237 nm

Example 6 (Not According to the Invention)

[0242] Example 6 was carried out according to the protocol of example 1 using a mixture of purified soybean oil (50 g) and purified medium-chain triglycerides (50 g) instead of purified soybean oil (100 g).

[0243] Analytical data:

[0244] Homogenous, white liquid

[0245] pH value: 7.5

[0246] Average particle size (PdI): 270 nm (0.023)

[0247] Stability: 3 m at 45° C.:

[0248] White liquid with small oil droplets on the surface

[0249] pH value: 6.9

[0250] Average particle size: 259 nm

[0251] 12 m at room temperature:

[0252] White liquid with small oil droplets on the surface

[0253] pH value: 7.9

[0254] Average particle size: 276 nm

Example 7

[0255] Glycerol and water for injection were mixed. Phospholipid composition P1 (6.0 g) and DMPG-Na (0.30 g) were added and the mixture was stirred at 50° C., until the phospholipids were completely dispersed. A mixture of purified soybean oil (50 g) and purified medium- chain triglycerides (50 g) was heated separately to 60° C. The aqueous phase was mixed with a high-shear mixer at 10.000 rpm. Mixing was continued while the heated oil phase was added slowly. pH was adjusted to 8.5 by adding a sodium hydroxide solution in water (0.5M). The resulting pre-emulsion was then homogenized using a high-pressure homogenizer in five passes at a pressure of 800 bar. Temperature was kept at 50° C. to 70° C. during homogenization. Prior to the 5.sup.th pass, pH was again adjusted to 8.5. After the homogenization, the emulsion was cooled below 30° C., filled in glass vials and autoclaved.

[0256] Analytical data:

[0257] Homogenous, white liquid

[0258] pH value: 7.8

[0259] Average particle size (PdI): 227 nm (0.065)

Example 8

[0260] Example 8 was carried out according to the protocol of example 3 using a mixture of purified soybean oil (50 g) and purified medium-chain triglycerides (50 g) instead of purified soybean oil (100 g). As in example 3 a homogeneous mixture of phospholipid composition P1 and DMPG-Na in a weight ratio of 20:1 was used (6 g of P5 instead of P1).

[0261] Analytical data:

[0262] Homogenous, white liquid

[0263] pH value: 7.5

[0264] Average particle size (PdI): 232 nm (0.026)

[0265] Stability: 3 m at 45° C.:

[0266] Homogenous, white liquid

[0267] pH value: 7.2

[0268] Average particle size: 212 nm

Example 9

[0269] Example 9 was carried out according to the protocol of example 1 using a mixture of purified soybean oil (50 g) and purified medium-chain triglycerides (50 g) instead of purified soybean oil (100 g) and using phospholipid composition P3 instead of the phospholipid composition P1.

[0270] Analytical data:

[0271] Homogenous, white liquid

[0272] pH value: 7.8

[0273] Average particle size (PdI): 240 nm (0.002)

[0274] Stability: 3 m at 45° C.:

[0275] Homogenous, white liquid

[0276] pH value: 7.1

[0277] Average particle size: 224 nm

Example 10 (Not According to the Invention)

[0278] Glycerol and water for injection were mixed. Phospholipid composition P2 (6.0 g) was added and the mixture was stirred at 50° C., until the phospholipids were completely dispersed. A mixture of purified soybean oil (50 g) and purified medium-chain triglycerides (50 g) was heated separately to 60° C. The aqueous phase was mixed with a high-shear mixer at 10.000 rpm. Mixing was continued while the heated oil phase was added slowly. pH was adjusted to 8.5 by adding a sodium hydroxide solution in water (0.5M). After pH adjustment, the pre-emulsion turned green. The pre-emulsion was then homogenized using a high-pressure homogenizer in five passes at a pressure of 800 bar. Temperature was kept at 50° C. to 70° C. during homogenization. Prior to the 5.sup.th pass, pH was again adjusted to 8.5. After the homogenization, the emulsion was cooled below 30° C., filled in glass vials and autoclaved. After autoclaving, the green color had faded and the emulsion had an off-white to greyish color.

[0279] Analytical data:

[0280] Homogenous, off-white liquid

[0281] pH value: 7.6

[0282] Average particle size (PdI): 243 nm (0.005)

[0283] Stability: 3 m at 45° C.:

[0284] Homogenous, greyish liquid

[0285] pH value: 7.0

[0286] Average particle size: 230 nm

[0287] 12 m at room temperature:

[0288] Greyish liquid with small oil droplets on the surface

[0289] pH value: 7.7

[0290] Average particle size: 265 nm

Example 11

[0291] Glycerol and water for injection were mixed. Phospholipid composition P1 (6.0 g) and DMPG-Na (0.30 g) were added and the mixture was stirred at 50° C., until the phospholipids were completely dispersed. Purified soybean oil (100 g) was heated separately to 60° C. Glycine (0.05 g) and lysine dihydrochloride (0.05 g) were added to the water phase and stirring was continued, until the amino acids were dissolved (ca. 2 min). The aqueous phase was mixed with a high-shear mixer at 10.000 rpm. Mixing was continued while the heated oil phase was added slowly. pH was adjusted to 7.5 by adding a sodium hydroxide solution in water (0.5M). The resulting pre-emulsion was then homogenized using a high-pressure homogenizer in five passes at a pressure of 800 bar. Temperature was kept at 50° C. to 70° C. during homogenization. Prior to the 5.sup.th pass, pH was adjusted to 8.5. After the homogenization, the emulsion was cooled below 30° C., filled in glass vials and autoclaved.

[0292] Analytical data:

[0293] Homogenous, white liquid

[0294] pH value: 8.6

[0295] Average particle size (PdI): 245 nm (0.100)

[0296] Stability: 3 m at 45° C.:

[0297] Homogenous, white liquid

[0298] pH value: 7.9

[0299] Average particle size: 240 nm

[0300] 12 m at room temperature:

[0301] Homogenous, white liquid

[0302] pH value: 8.4

[0303] Average particle size: 262 nm

Example 12 (Not According to the Invention)

[0304] Glycerol and water for injection were mixed. Phospholipid composition P4 (6.0 g) and DMPG-Na (0.30 g) were added and the mixture was stirred at 50° C., until the phospholipids were completely dispersed. Purified soybean oil (100 g) was heated separately to 60° C. Glycine (0.05 g) and lysine dihydrochloride (0.05 g) were added to the water phase and stirring was continued, until the amino acids were dissolved (ca. 2 min). The aqueous phase was mixed with a high-shear mixer at 10.000 rpm. Mixing was continued while the heated oil phase was added slowly. pH was adjusted to 7.7 by adding a sodium hydroxide solution in water (0.5M). After pH adjustment, the pre-emulsion turned green. The resulting pre-emulsion was then homogenized using a high-pressure homogenizer in five passes at a pressure of 800 bar. Temperature was kept at 50° C. to 70° C. during homogenization. Prior to the 5.sup.th pass, pH was adjusted to 8.5. After the homogenization, the emulsion was cooled below 30° C., filled in glass vials and autoclaved. After autoclaving, the green color had faded and the emulsion had a greyish color.

[0305] Analytical data:

[0306] Homogenous, greyish liquid

[0307] pH value: 8.6

[0308] Average particle size (PdI): 240 nm (0.033)

[0309] Stability: 3 m at 45° C.:

[0310] Homogenous, greyish liquid

[0311] pH value: 7.7

[0312] Average particle size: 234 nm

[0313] 12 m at room temperature:

[0314] Greyish liquid with small oil droplets on the surface

[0315] pH value: 8.2

[0316] Average particle size: 260 nm

Example 13

[0317] Example 13 was carried out according to the protocol of example 11 using a mixture of purified soybean oil (50 g) and purified medium-chain triglycerides (50 g) instead of purified soybean oil (100 g).

[0318] Analytical data:

[0319] Homogenous, white liquid

[0320] pH value: 8.3

[0321] Average particle size (PdI): 226 nm (0.102)

[0322] Stability: 3 m at 45° C.:

[0323] Homogenous, white liquid

[0324] pH value: 8.1

[0325] Average particle size: 224 nm

Example 14 (Not According to the Invention)

[0326] Example 14 was carried out according to the protocol of example 12 using a mixture of purified soybean oil (50 g) and purified medium-chain triglycerides (50 g) instead of purified soybean oil (100 g). First pH adjustment was pH 7.8 instead of pH 7.7. After first pH adjustment, the pre-emulsion turned green. After autoclaving, the green color had faded and the emulsion had a greyish appearance.

[0327] Analytical data:

[0328] Homogenous, greyish liquid

[0329] pH value: 8.3

[0330] Average particle size (PdI): 237 nm (0.014)

[0331] Stability: 3 m at 45° C.:

[0332] Homogenous, greyish liquid

[0333] pH value: 7.4

[0334] Average particle size: 227 nm

[0335] 12 m at room temperature:

[0336] Greyish liquid with small oil droplets on the surface

[0337] pH value: 8.1

[0338] Average particle size: 224 nm

Example 15

[0339] Example 15 was carried out according to the protocol of example 2 using 0.4 g of DMPG-Na (0.08% b.w. based on the emulsion) instead of 0.3 g of DMPG-Na.

[0340] Analytical data:

[0341] Homogenous, white liquid

[0342] pH value: 7.2

[0343] Average particle size (PdI): 229 nm (0.105)

[0344] Stability: 3 m at 45° C.:

[0345] Homogenous, white liquid

[0346] pH value: 6.8

[0347] Average particle size: 244 nm

[0348] 18 m at room temperature:

[0349] Homogenous, white liquid

[0350] pH value: 7.8

[0351] Average particle size: 246 nm

Example 16

[0352] Example 16 was carried out according to the protocol of example 2 using 0.1 g of DMPG-Na (0.02% b.w. based on the emulsion) instead of 0.3 g of DMPG-Na.

[0353] Analytical data:

[0354] Homogenous, white liquid

[0355] pH value: 6.9

[0356] Average particle size (PdI): 221 nm (0.043)

[0357] Stability: 3 m at 45° C.:

[0358] Homogenous, white liquid

[0359] pH value: 6.8

[0360] Average particle size: 239 nm

[0361] 18 m at room temperature:

[0362] Homogenous, white liquid

[0363] pH value: 7.3

[0364] Average particle size: 244 nm

Example 17

[0365] Example 17 was carried out according to the protocol of example 7 using 0.4 g of DMPG-Na (0.08% b.w. based on the emulsion) instead of 0.3 g of DMPG-Na.

[0366] Analytical data:

[0367] Homogenous, white liquid

[0368] pH value: 7.7

[0369] Average particle size (PdI): 200 nm (0.032)

[0370] Stability: 3 m at 45° C.:

[0371] Homogenous, white liquid

[0372] pH value: 7.6

[0373] Average particle size: 218 nm

[0374] 3 m at room temperature:

[0375] Homogenous, white liquid

[0376] pH value: 7.9

[0377] Average particle size: 209 nm

Example 18

[0378] Example 18 was carried out according to the protocol of example 7 using 0.1 g of DMPG-Na (0.02% b.w. based on the emulsion) instead of 0.3 g of DMPG-Na.

[0379] Analytical data:

[0380] Homogenous, white liquid

[0381] pH value: 7.7

[0382] Average particle size (PdI): 209 nm (0.035)

[0383] Stability: 3 m at 45° C.:

[0384] Homogenous, white liquid

[0385] pH value: 7.2

[0386] Average particle size: 218 nm

[0387] 3 m at room temperature:

[0388] Homogenous, white liquid

[0389] pH value: 7.2

[0390] Average particle size: 225 nm

Example 19

[0391] Example 19 was carried out according to the protocol of example 3 using 6.0 g of phospholipid composition P6 instead of phospholipid composition P5.

[0392] Analytical data:

[0393] Homogenous, white liquid

[0394] pH value: 7.8

[0395] Average particle size (PdI): 232 nm (0.042)

[0396] Stability: 3 m at 45° C.:

[0397] Homogenous, white liquid

[0398] pH value: 7.7

[0399] Average particle size: 246 nm

[0400] 3 m at room temperature:

[0401] Homogenous, white liquid

[0402] pH value: 8.2

[0403] Average particle size: 247 nm

Example 20

[0404] Example 20 was carried out according to the protocol of example 3 using 6.0 g of phospholipid composition P7 instead of phospholipid composition P5.

[0405] Analytical data:

[0406] Homogenous, white liquid

[0407] pH value: 7.7

[0408] Average particle size (PdI): 222 nm (0.096)

[0409] Stability: 3 m at room temperature:

[0410] Homogenous, white liquid

[0411] pH value: 8.0

[0412] Average particle size: 245 nm

Example 21

[0413] Example 21 was carried out according to the protocol of example 8 using 6.0 g of phospholipid composition P6 instead of phospholipid composition P5.

[0414] Analytical data:

[0415] Homogenous, white liquid

[0416] pH value: 7.6

[0417] Average particle size (PdI): 210 nm (0.013)

[0418] Stability: 3 m at room temperature:

[0419] Homogenous, white liquid

[0420] pH value: 8.1

[0421] Average particle size: 221 nm

Example 22

[0422] Example 22 was carried out according to the protocol of example 8 using 6.0 g of phospholipid composition P7 instead of phospholipid composition P5.

[0423] Analytical data:

[0424] Homogenous, white liquid

[0425] pH value: 7.8

[0426] Average particle size (PdI): 206 nm (0.033)

[0427] Stability: 3 m at room temperature:

[0428] Homogenous, white liquid

[0429] pH value: 8.2

[0430] Average particle size: 219 nm

Example 24

[0431] Example 24 was carried out according to the protocol of example 3 using 6.0 g of phospholipid composition P8 instead of phospholipid composition P5.

[0432] Analytical data:

[0433] Homogenous, white liquid

[0434] pH value: 8.2

[0435] Average particle size (PdI): 212 nm (0.061)

[0436] Stability: 3 m at 45° C.:

[0437] Homogenous, white liquid

[0438] pH value: 7.7

[0439] Average particle size: 245 nm

[0440] 6 m at room temperature:

[0441] Homogenous, white liquid

[0442] pH value: 8.0

[0443] Average particle size: 245 nm

Example 25

[0444] Example 25 was carried out according to the protocol of example 7 using 6.0 g of phospholipid composition P1 and 0.3 g of DOPS-NA instead of DMPG-Na.

[0445] Analytical data:

[0446] Homogenous, white liquid

[0447] pH value: 8.2

[0448] Average particle size (PdI): 216 nm (0.071)

[0449] Stability: 3 m at 45° C.:

[0450] Homogenous, white liquid

[0451] pH value: 7.3

[0452] Average particle size: 221 nm

Example 26

[0453] Example 26 was carried out according to the protocol of example 8 using 6.0 g of phospholipid composition P8 instead of phospholipid composition P5.

[0454] Analytical data:

[0455] Homogenous, white liquid

[0456] pH value: 8.0

[0457] Average particle size (PdI): 203 nm (0.013)

[0458] Stability: 3 m at 45° C.:

[0459] Homogenous, white liquid

[0460] pH value: 7.3

[0461] Average particle size: 226 nm

[0462] 3 m at room temperature:

[0463] Homogenous, white liquid

[0464] pH value: 7.8

[0465] Average particle size: 228 nm

Example 27

[0466] Example 27 was carried out according to the protocol of example 2 using additionally 0.15 g of sodium oleate (0.03% b.w. based on the emulsion). The sodium oleate was added together with phospholipid composition P1 (6.0 g) and DMPG-Na (0.3 g) to the water/glycerine mixture.

[0467] Analytical data:

[0468] Homogenous, white liquid

[0469] pH value: 8.6

[0470] Average particle size (PdI): 229 nm (0.102)

[0471] Stability: 6 w at 45° C.:

[0472] Homogenous, white liquid

[0473] pH value: 8.0

[0474] Average particle size: 240 nm

Example 28

[0475] Example 28 was carried out according to the protocol of example 7 using additionally 0.15 g of sodium oleate (0.03% b.w. based on the emulsion). The sodium oleate was added together with phospholipid composition P1 (6.0 g) and DMPG-Na (0.3 g) to the water/glycerine mixture.

[0476] Analytical data:

[0477] Homogenous, white liquid

[0478] pH value: 8.5

[0479] Average particle size (PdI): 202 nm (0.064)

[0480] Stability: 6 w at 45° C.:

[0481] Homogenous, white liquid

[0482] pH value: 7.7

[0483] Average particle size: 208 nm

Example 29

[0484] Example 29 was carried out according to the protocol of example 4 using additionally 0.15 g of sodium oleate (0.03% b.w. based on the emulsion). The sodium oleate was added together with phospholipid composition P3 (6.0 g) to the water/glycerine mixture.

[0485] Analytical data:

[0486] Homogenous, white liquid

[0487] pH value: 8.3

[0488] Average particle size (PdI): 236 nm (0.081)

[0489] Stability: 3 m at 45° C.:

[0490] Homogenous, white liquid

[0491] pH value: 7.7

[0492] Average particle size: 230 nm

[0493] 12 m at room temperature:

[0494] Homogenous, white liquid

[0495] pH value: 7.9

[0496] Average particle size: 235 nm

[0497] Example 30 was carried out according to the protocol of example 9 using additionally 0.15 g of sodium oleate (0.03% b.w. based on the emulsion). The sodium oleate was added together with phospholipid composition P3 (6.0 g) to the water/glycerine mixture.

[0498] Analytical data:

[0499] Homogenous, white liquid

[0500] pH value: 8.3

[0501] Average particle size (PdI): 215 nm (0.056)

[0502] Stability: 6 w at 45° C.:

[0503] Homogenous, white liquid

[0504] pH value: 7.6

[0505] Average particle size: 234 nm