CA2104930A1 - Nutritive composition and a process for its preparation - Google Patents
Nutritive composition and a process for its preparationInfo
- Publication number
- CA2104930A1 CA2104930A1 CA002104930A CA2104930A CA2104930A1 CA 2104930 A1 CA2104930 A1 CA 2104930A1 CA 002104930 A CA002104930 A CA 002104930A CA 2104930 A CA2104930 A CA 2104930A CA 2104930 A1 CA2104930 A1 CA 2104930A1
- Authority
- CA
- Canada
- Prior art keywords
- emulsion
- composition
- nutritive
- prepared
- ratio
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
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Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0029—Parenteral nutrition; Parenteral nutrition compositions as drug carriers
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23J—PROTEIN COMPOSITIONS FOR FOODSTUFFS; WORKING-UP PROTEINS FOR FOODSTUFFS; PHOSPHATIDE COMPOSITIONS FOR FOODSTUFFS
- A23J7/00—Phosphatide compositions for foodstuffs, e.g. lecithin
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/10—Foods or foodstuffs containing additives; Preparation or treatment thereof containing emulsifiers
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/18—Lipids
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/18—Lipids
- A23V2250/184—Emulsifier
- A23V2250/1846—Phosphatidyl Choline
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/18—Lipids
- A23V2250/184—Emulsifier
- A23V2250/1848—Phosphatidyl Ethanolamine
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Nutrition Science (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Mycology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dermatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Biochemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Epidemiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- General Preparation And Processing Of Foods (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Edible Oils And Fats (AREA)
Abstract
Abstract A nutritive composition and a process for its production The invention relates to a nutritive composition suitable for use in parenteral feeding, to which a small quantity of an emulsifying compound is added. The invention also relates to a process for the preparation of this composition.
Description
21 O ~
This invention relates to a nutritive composition in the form of an oil-in-water emulsion preferably intended for parenteral administration. The invention also relates to a process for the production of this nutritive CompOSitiQn.
Nutritive compositions in the form of oil-in-water emulsions containing 20% lipids are known in principle. Nutritive compositions containing 10% lipids are also known. These nutritive compositions, which are intended for parenteral administration, have to meet strict requirements and, in particular, have to be completely sterile. Now, it is known that the effect of sterilization is in particular to destabilize the oil-in-water emulsions which thus separate into two or more phases. To solve this problem, an emulsifier is gener-ally added to the emulsion during its preparation.
Lecithin in particular is added as the emulsifier in a quantity of 1.2% to 2% by weight, enabling the nutritive composition to be sterilized without destabilization.
This is illustrated, for example, in the Article by Masson et al. published in Revue Française des Corps Gras (0ct. 1984) 10, 391-394.
Now, in nutritive compositions of low lipid content, the presence of a significant quantity of free phospholipids, which are the majority constituents of lecithin, gives rise to disadvantages. This is par-ticularly noticeable in the case of 10% emulsions in which the ratio of phospholipids to lipids can be of the order of 10 to 15:100. It has been found that, when there are too many free phosolipids in an emulsion, they tend to form micelles of which the effect is to de-stabilize the emulsion even further, particularly during sterilization.
. ,. :
- ~ .
:. . .
,:, ~ ., . . : ', .
This invention relates to a nutritive composition in the form of an oil-in-water emulsion preferably intended for parenteral administration. The invention also relates to a process for the production of this nutritive CompOSitiQn.
Nutritive compositions in the form of oil-in-water emulsions containing 20% lipids are known in principle. Nutritive compositions containing 10% lipids are also known. These nutritive compositions, which are intended for parenteral administration, have to meet strict requirements and, in particular, have to be completely sterile. Now, it is known that the effect of sterilization is in particular to destabilize the oil-in-water emulsions which thus separate into two or more phases. To solve this problem, an emulsifier is gener-ally added to the emulsion during its preparation.
Lecithin in particular is added as the emulsifier in a quantity of 1.2% to 2% by weight, enabling the nutritive composition to be sterilized without destabilization.
This is illustrated, for example, in the Article by Masson et al. published in Revue Française des Corps Gras (0ct. 1984) 10, 391-394.
Now, in nutritive compositions of low lipid content, the presence of a significant quantity of free phospholipids, which are the majority constituents of lecithin, gives rise to disadvantages. This is par-ticularly noticeable in the case of 10% emulsions in which the ratio of phospholipids to lipids can be of the order of 10 to 15:100. It has been found that, when there are too many free phosolipids in an emulsion, they tend to form micelles of which the effect is to de-stabilize the emulsion even further, particularly during sterilization.
. ,. :
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On the other hand, it has been found that, when a 10~ emulsion containing 1.2% lecithin is administered to infants, the concentration of triglycerides in the blood plasma increases considerably by comparlson with the increase obtained where a 20% emulsion is used.
This problem is addressed in the Article by Haumont et al. in "The Journal of Pediatrics" (1989), 115, 787-793.
An accumulation of cholesterol and low-density lipopro-teins in the blood is also observed.
The problem addressed by the present invention was to obviate these disadvantages and to provide a nutritive composition which would be stable, even after sterilizat~on, and which would contain a very small quantity of an emulsifying compound.
Accordingly, the present invention relates to a composition in the form of an oil-in-water emulsion containing at least 10% by weight lipids and at least 0.4% by weight of an emulsifying compound comprising phosphatidyl choline (PC) and phosphatidyl ethanolamine (PE) in a ratio of PC to PE of 2 to 10:1.
The present invention also relates to a process for the production of this composition, in which an aqueous phase and a lipid phase are prepared, at least 0.4% of an emulsifying compound comprising phosphatidyl choline (PC) and phosphatidyl ethanolamine (PE) in a ratio of PC to PE of 2 to 10l is added to one and/or the other of the phases, the two resulting phases are mixed to form an emulsion containing at least 10% by weight lipids and the emulsion obtained is sterilized.
It has been found that the use of an emulsifying compound comprising phosphatidyl choline and phosphati-dyl ethanolamine in a PC to PE ratio of 2 to 10:1 enables the quantity of emulsi~ier to be added to be considerably reduced, particularly in compositions of low lipid content, such as 10% emulsions. The use of `' ' . . : .' '.
2 ~ J ~ ~3 the emulsifying compound in question al50 enables amino acids to be added to the composition without causing destabilization during sterilization. Yet another advantage is that nutritive compositions can be prepared without any undesirable odour and/or colour by virtue of the small quantity of emulsifying compound added.
In the context of the invention, stability is understood to be the property of an emulsion whereby it has no tendency to separate into phases or into its constituents.
The features and advantages of the present invention will become apparent from the following description in which parts and percentages are by weight and the following abbreviations are used:
. PC : phosphatidyl choline PE : phosphatidyl ethanolamine.
To carry out the process according to the inven-tion, an oil-in-water emulsion is prepared in the form of a mixture of an aqueous phase and a lipid phase. The lipid phase may be formed by oils of vegetable origin, such as palm oil, corn oil, canola oil, soybean oil, ; olive oil and sunflower oil, or by oils of animal origin, such as butter oil or fish oil or even by medium-chain triglycerides. A mixture of these various oils may also be used. The aqueous phase consists mainly of water, preferably distilled or demineralized water, to which glucides may be added. The glucides may be selected from the group consisting of monosaccharides or polysaccharides, such as maltose, fructose or glu-cose, maltodextrins having a dextrose equivalent (DE) of 10 to 50 and preferably of the order of 45 and poly-alcohols, such as glycerol, sorbitol or xylitol.
The emulsion according to the invention is distinguished in particular by the fact that it contains ' ' .
- . - . .
.
2~
at least 10% lipids and a~ least 0.4% o~ an emulsifying compound comprising phosphatidyl choline and phosphati-dyl ethanolamine in a ratio of PC ~o PE of 2 to lO:l~
Depending on its solubility, this emulsifying compound may be added to the aqueous phase or to the lipid phase before they are mixed.
To prepare the oil-in-water emulsion, the aqueous and lipid phases may be separately heated with con-tinuous stirring to a temperature in the range from 40 to 60C, preferably in an inert gas atmospher2, for example in a nitrogen atmosphere, in order to avoid possible contamination or oxidation of the fats. The two phases may then be mixed, for example by addition of lO to 40 parts lipid phase to lO0 parts aqueous phase with continuous stirring at a temperature in the range from 40 to 60C.
To improve the stability of the emulsion ob-tained, the average size of the droplets of the lipid phase may be reduced, for example by homogenization. It is also possible in this way to establish the narrowest possible particle size distribution. To this end, the emulsion may be prehomogenized under a pressure of 15 to 25 bar to obtain an average droplet size of the order of l.5 to 2.5 ~m and then homogenized under high pressure (2 to 1200 bar), for example in a homogenizer. This last step may be repeated several times to obtain an emulsion of which the average droplet size of the lipid phase is of the order of 0.15 to 0.35 ~m. The homogeni-zation step is preferably carried out at 40 to 60C.
Th~ homogenized emulsion is then continuously stirred in an inert gas atmosphere, for example of nitrogen. After homogenization, the emulsion is left to cool to ambient temperature and then neutralized, for example by addi-tion of sodium hydroxide, t4 obtain a pH value of 7 to 7.5. The emulsion may then be sterilized, for example .. - '~', ~ .:-,,:
.
.
~lo~ 3n by heat treatment for 8 to 30 minutes at 120 to 130C, and then packed under aseptic conditions in cans, cartons or bottles.
An oil-in-water emulsion havin~ a lipid content of at least 10% is obtained in this way. The emulsion, which contains at least 0.~% of an emulsifying compound comprising PC and PE in a ratio of PC to PE of 2 to 10:1, is capable of retaining its stability for long periods.
The emulsion may be used in the field of paren-teral feeding either as such or after dilution.
Thus, in one particular application, a nutritive composition containing 1 part emuIsion to 0-15 parts wateroptionally containing an amino acid source may be prepared from the emulsion.
The amino acid source may be added, preferably in the form of an aqueous solution, to the prepared emul-sion eithar before or after homogeni~ation and/or sterilization. The amino acid source may also be addad to the aqueous phase before preparation of the emulsion.
The amino acid source may be formed, for example, b~
amino acids and/or peptides. It has been found that, by virtue of the present invention, up to 6% of an amino acid source may be added to a 10 or 20% emulsion of lipids without causing destabilization of the composi-tion after sterilization. A stable nutritive composi-tion containing amino acids which is suitable for use in the ~ield of parenteral feeding is thus obtained after sterilization.
The invention is illustrated by khe ~ollowing Examples in which the various measurements are carried out as follows:
~' ` ; ' 2 1 ~
1) Measurement of osmolality Osmolalitv is understood to be the number of osmotically active moles per kilogram of product taken as reference, in the present case per kilogram,of water (unit Osm/kg water). Osmolality is measured with a Roe~ling osmometer by measurement of the cryoscopic depression of the solution using pure water as refer-ence.
2) Measurement,of,t e fats content The fats content of the composition is determined by measurement of the quantity of lipids as follows:
~ ., - an exact quantity - between 10 and 50 g - of the liquid to be analyzed is removed, - this liquid is diluted with 20 ml of a 10%
aqueous NaCl solution, - a pH value of 3 is adjusted by addition of a 0.1 N aqueous HCl solution, - the lipids are extracted four times with 50 ml of a solution containing parts n-hexane and 2 parts isopropanol, ;
- the organic phase obtained is washed with 30 ml 10% NaCl while the aqueous phase obtained is washed with 30 ml n-hexane, - the organic phases aræ. combined and dried over anhydrous sodium sulfate and then filtered.
The organic solvents are then evaporated under 30 reduced pressure and the quantity of lipids is obtained by weighing. The fats content T, expressed in ~, is obtained by establishing a ratio between the weighed quantity of lipids and the quantity of liquid initially removed.
:: , : .. . .~ :
,, . . . . -' ~ " ' :: ' , :- ' : . ' ~ :
.
- , : : . , .. . . . .
2~0~
On the other hand, it has been found that, when a 10~ emulsion containing 1.2% lecithin is administered to infants, the concentration of triglycerides in the blood plasma increases considerably by comparlson with the increase obtained where a 20% emulsion is used.
This problem is addressed in the Article by Haumont et al. in "The Journal of Pediatrics" (1989), 115, 787-793.
An accumulation of cholesterol and low-density lipopro-teins in the blood is also observed.
The problem addressed by the present invention was to obviate these disadvantages and to provide a nutritive composition which would be stable, even after sterilizat~on, and which would contain a very small quantity of an emulsifying compound.
Accordingly, the present invention relates to a composition in the form of an oil-in-water emulsion containing at least 10% by weight lipids and at least 0.4% by weight of an emulsifying compound comprising phosphatidyl choline (PC) and phosphatidyl ethanolamine (PE) in a ratio of PC to PE of 2 to 10:1.
The present invention also relates to a process for the production of this composition, in which an aqueous phase and a lipid phase are prepared, at least 0.4% of an emulsifying compound comprising phosphatidyl choline (PC) and phosphatidyl ethanolamine (PE) in a ratio of PC to PE of 2 to 10l is added to one and/or the other of the phases, the two resulting phases are mixed to form an emulsion containing at least 10% by weight lipids and the emulsion obtained is sterilized.
It has been found that the use of an emulsifying compound comprising phosphatidyl choline and phosphati-dyl ethanolamine in a PC to PE ratio of 2 to 10:1 enables the quantity of emulsi~ier to be added to be considerably reduced, particularly in compositions of low lipid content, such as 10% emulsions. The use of `' ' . . : .' '.
2 ~ J ~ ~3 the emulsifying compound in question al50 enables amino acids to be added to the composition without causing destabilization during sterilization. Yet another advantage is that nutritive compositions can be prepared without any undesirable odour and/or colour by virtue of the small quantity of emulsifying compound added.
In the context of the invention, stability is understood to be the property of an emulsion whereby it has no tendency to separate into phases or into its constituents.
The features and advantages of the present invention will become apparent from the following description in which parts and percentages are by weight and the following abbreviations are used:
. PC : phosphatidyl choline PE : phosphatidyl ethanolamine.
To carry out the process according to the inven-tion, an oil-in-water emulsion is prepared in the form of a mixture of an aqueous phase and a lipid phase. The lipid phase may be formed by oils of vegetable origin, such as palm oil, corn oil, canola oil, soybean oil, ; olive oil and sunflower oil, or by oils of animal origin, such as butter oil or fish oil or even by medium-chain triglycerides. A mixture of these various oils may also be used. The aqueous phase consists mainly of water, preferably distilled or demineralized water, to which glucides may be added. The glucides may be selected from the group consisting of monosaccharides or polysaccharides, such as maltose, fructose or glu-cose, maltodextrins having a dextrose equivalent (DE) of 10 to 50 and preferably of the order of 45 and poly-alcohols, such as glycerol, sorbitol or xylitol.
The emulsion according to the invention is distinguished in particular by the fact that it contains ' ' .
- . - . .
.
2~
at least 10% lipids and a~ least 0.4% o~ an emulsifying compound comprising phosphatidyl choline and phosphati-dyl ethanolamine in a ratio of PC ~o PE of 2 to lO:l~
Depending on its solubility, this emulsifying compound may be added to the aqueous phase or to the lipid phase before they are mixed.
To prepare the oil-in-water emulsion, the aqueous and lipid phases may be separately heated with con-tinuous stirring to a temperature in the range from 40 to 60C, preferably in an inert gas atmospher2, for example in a nitrogen atmosphere, in order to avoid possible contamination or oxidation of the fats. The two phases may then be mixed, for example by addition of lO to 40 parts lipid phase to lO0 parts aqueous phase with continuous stirring at a temperature in the range from 40 to 60C.
To improve the stability of the emulsion ob-tained, the average size of the droplets of the lipid phase may be reduced, for example by homogenization. It is also possible in this way to establish the narrowest possible particle size distribution. To this end, the emulsion may be prehomogenized under a pressure of 15 to 25 bar to obtain an average droplet size of the order of l.5 to 2.5 ~m and then homogenized under high pressure (2 to 1200 bar), for example in a homogenizer. This last step may be repeated several times to obtain an emulsion of which the average droplet size of the lipid phase is of the order of 0.15 to 0.35 ~m. The homogeni-zation step is preferably carried out at 40 to 60C.
Th~ homogenized emulsion is then continuously stirred in an inert gas atmosphere, for example of nitrogen. After homogenization, the emulsion is left to cool to ambient temperature and then neutralized, for example by addi-tion of sodium hydroxide, t4 obtain a pH value of 7 to 7.5. The emulsion may then be sterilized, for example .. - '~', ~ .:-,,:
.
.
~lo~ 3n by heat treatment for 8 to 30 minutes at 120 to 130C, and then packed under aseptic conditions in cans, cartons or bottles.
An oil-in-water emulsion havin~ a lipid content of at least 10% is obtained in this way. The emulsion, which contains at least 0.~% of an emulsifying compound comprising PC and PE in a ratio of PC to PE of 2 to 10:1, is capable of retaining its stability for long periods.
The emulsion may be used in the field of paren-teral feeding either as such or after dilution.
Thus, in one particular application, a nutritive composition containing 1 part emuIsion to 0-15 parts wateroptionally containing an amino acid source may be prepared from the emulsion.
The amino acid source may be added, preferably in the form of an aqueous solution, to the prepared emul-sion eithar before or after homogeni~ation and/or sterilization. The amino acid source may also be addad to the aqueous phase before preparation of the emulsion.
The amino acid source may be formed, for example, b~
amino acids and/or peptides. It has been found that, by virtue of the present invention, up to 6% of an amino acid source may be added to a 10 or 20% emulsion of lipids without causing destabilization of the composi-tion after sterilization. A stable nutritive composi-tion containing amino acids which is suitable for use in the ~ield of parenteral feeding is thus obtained after sterilization.
The invention is illustrated by khe ~ollowing Examples in which the various measurements are carried out as follows:
~' ` ; ' 2 1 ~
1) Measurement of osmolality Osmolalitv is understood to be the number of osmotically active moles per kilogram of product taken as reference, in the present case per kilogram,of water (unit Osm/kg water). Osmolality is measured with a Roe~ling osmometer by measurement of the cryoscopic depression of the solution using pure water as refer-ence.
2) Measurement,of,t e fats content The fats content of the composition is determined by measurement of the quantity of lipids as follows:
~ ., - an exact quantity - between 10 and 50 g - of the liquid to be analyzed is removed, - this liquid is diluted with 20 ml of a 10%
aqueous NaCl solution, - a pH value of 3 is adjusted by addition of a 0.1 N aqueous HCl solution, - the lipids are extracted four times with 50 ml of a solution containing parts n-hexane and 2 parts isopropanol, ;
- the organic phase obtained is washed with 30 ml 10% NaCl while the aqueous phase obtained is washed with 30 ml n-hexane, - the organic phases aræ. combined and dried over anhydrous sodium sulfate and then filtered.
The organic solvents are then evaporated under 30 reduced pressure and the quantity of lipids is obtained by weighing. The fats content T, expressed in ~, is obtained by establishing a ratio between the weighed quantity of lipids and the quantity of liquid initially removed.
:: , : .. . .~ :
,, . . . . -' ~ " ' :: ' , :- ' : . ' ~ :
.
- , : : . , .. . . . .
2~0~
3) Determination of the stability index In order quantitatively to characterize the physical stability of the nutritive compositions pre-pared, the stability index (SI) is determined as fol-lows:
- a first sample of the prepared composition is removed and its fats content T1 is determined, - a second sample is removed and centrifuged for 15 minutes at 1000 r.p.m~/25C; this yenerally results in separation into two more or less distinct phases; ,~ '' - the fats content T2 of the 'lower phase of the centrifuged sample is determined and - the stability index SI (in %) is obtained by ~, establishing the ratio: T 2 x 100 4) Preparation of the PC/PE compounds Some of the emulsifying compounds used in the following Examples were prepared as follows:
- a quantity Ql of lecithin with a PC:PE ratio of 4 :1 is weighed and dissolved in 100 ml of a 2:1 mixture of dichloromethane and methanol, - a quantity Q2 of lecithin with a PC:PE ratio of 10:8 (or a quantity Q3 of pure PE3 is added and the whole is thoroughly mixed, - the solvent is evaporated to dryness, ~' - 100 ml water are added and the product obtained is redispersed with stirring and then freeze-dried.
., . . ~
; ~ ' " -2 1 o ~ ~ ? n Quantities to be added for the various PC:PE mixtures:
PC:PE 2.5.1 6:1 8:1 Q1 1 ~2 g 1 g ~2 1.832 g 3.223 g Q3 0.125 g Example An aqueous phase is prepared by mixing 14.6 ml ~0 water, 0.4 ml glycerol and egg lecithin with a PC:P~
ratio of 4.1:1 in the quantity defined in the following Table with stirring at 45C. 3.8 g of a soybean oil are then slowly added to this aqueous phase with continuous stirring, the temperature being kept at approximately 45~.
An emulsion containing 20~ lipids is obtained in this way and is subsequently homogenized after five pas- ~-sages through a suitable apparatus of the "Microfluid-izer" type under a pressure of 1100 bar and at a temper-ature of 20C to 50C in order to obtain an average droplet size in the lipid phase of 250 to 950 nm. The pH of the emulsion thus prepared is ad~usted to 7.4 with 0.5 N sodium hydroxide, after which the emulsion is packed in 100 ml bottles which are sterilized for 9 minutes at 126C.
The osmolality and the pH of the emulsion are determined before and after sterilization. The stabil-ity of the emulsion is also Yisually observed.
The following results are obtained:
Al A2 A3 A4 A5 A6 % 1.28 1.05 0.83 0.62 0.41 0.21 Osmo 1 342 346 351 327 353 327 pH 1 3.87 3.99 4017 4.67 5.06 5.82 Osmo 2 343 349 353 325 353 328 ~.
2 i ~ 3~
Al A2 A3 A4 A5 A6 pH 2 ~.76 5. ns 5.08 5.3~ 5.29 5.23 T0 -~ t + ~ +
T1 + ~ +
T2 +
~ : percentage of lecithin in the emulsion Osmo 1 : osmolality before sterilization (in mOsm/kg) pH 1 : pH before sterilization Osmo 2 : osmolality after sterilization (in mOsm/kg) pH 2 : pH after sterilization T0 : observation just after prepara~ion of th emulsion Tl : observation after storage for 1 month at ambient temperature T2 : observation after storage for 2 months at ambient temperature + : stable emulsion 0 : slight trace of separation, emulsion homogeneous again after stirring 1 : incipient separation, flocculation and/or sedimen-tation - : distinct separation, emulsion irreversibly broken Accordingly, it can be selen that the addition of a quantity of 0.21% lecithin with a PC:PE ratio of 4.1~il is not sufficient to obtain an emulsion which remains stable after storage for one or two monthsO The addi- .-tion of a quantity of 0.4% of a lecithin having a PC:PE
ratio of 4.1:1 is sufficient to keep the emulsion stable for at least two months.
A nutritive composition is then prepared. An aqueous solution containing amino acids, namely L
leucine, glycine, L-alanine and L-proline, in a total ,. . . .,, , , . . - . . :. ~ .: . : :i ~ :
:: , :
:. . - . .
: , , - .:: ~.:. . :
2 ~
quantity of 6.0 g in 75 ml water is initially prepared.
81 g of this aqueous solution are added to l9 g of the emulsion prepared as described above. The nutritive composition obtained is sterilized for 1 minute at 126C.
The osmolality and pH of the nutritive composi-tion before and after sterilization are determined. The stability of the composition is also visually observed.
The following results are obtained:
Bl B2 B3 B4 B5 B6 % 0.2~ 0.20 0.16 0.12 0.08 0.04 Osmo 1 753 784 611 752 755 746 pH 1 8.01 8.09 8.08 8.16 8.25 8.35 Osmo 2 756 789 614 752 758 744 pH 2 8.07 8.09 7.99 8.02 8.21 8.33 T0 ~ + + + + o T2 o 0 0 % : percentage of lecithin in the final nutritive composition Osmo 1 : osmolality before stlerilization (in mOsm/kg) Osmo 2 : osmolality after sterilization (in mOsm/kg) 25 pH l/pH 2 : pH before/after sterilization T0 : observation just after preparation of the composition Tl/T2 : observation after storage for 1 month and 2 months at ambient temperature + : stable nutritive composition 0 : slight trace of separation, emulsion homogen~ous again after stirring l : incipient separation, flocculation and/or sedimen-~':
-.............................. . . ~ -:
.: . . - : .. : -- .
. .. .... . .
. ~
~, , '.,:: ~ .
21~'~9 3~
tation - : distinct separation, emulsion irreversibly broken Accordingly, it can be seen that the addition of a quantity of 0.04% lecithin with a PC:PE ratio of 4.1:1 is not sufficient to obtain a stable nutritive composi tion. The addition of a quantity of 0.08% lecithin with a PC:PE ratio of 4.1:1 is sufficient to obtain a stable nutritive composition containing 20% lipids and also amino acids, but not to keep it stable during storage for several months.
Ex~mple 2 An aqueous phase is prepared by mixing 14.6 ml water, 0.4 ml glycerol and egg lecithin with a PC:PE
ratio of 4.8:1 in the quantity defined in the following Table with stirring at 4~C. 3.8 g of a soybean oil are slowly added to the aqueous phase thus prepared with continuous stirring, the temperature being kept at approximately 45C. An emulsion containing 20~ lipids is obtained in this way and is homogenized in the same way as before to obtain an average droplet size in the lipid phase of 250 to ~50 nm. The pH of the emulsion thus prepared is adjusted to 7.4 with 0.5 N sodium hydroxide solution, after which the emulsion is packed in 100 ml bottles which are sterilized for 9 minutes at 126C.
The osmolality and pH of the emulsion are deter-mined before and after sterilization. The stability of the emulsion is also visually observed: ~
The following results are obtainedo Cl C2 C3 C4 C5 C6 % 1.28 1.05 0.83 0.62 0.41 0.21 Osmo 1 333 321 331 341 341 376 . ~
, - -; :
.
. ' ' ' .
- : ., : . . , 2 ~ 3 t3 f~
C1 C2 C3 C~ C5 C6 p~ 1 ~.26 ~.58 ~.59 5.18 5.05 6.20 Osmo 2 331 325 333 342 339 377 pH 2 5.33 5.68 6.02 5.41 5.52 5.30 T0 + + + ~ + o Tl + + -~ + -~ -T2 + + + 1 - -% : percentage of lecithin in the emulsion Osmo 1 : osmolality before sterilization (in mOsm/kg) Osmo 2 : osmolality after sterilization (in mOsm/kg) pH l/p~ 2 : pH before/after sterilization TO : observation just after preparation of the emulsion Tl/T2 : observation after storage for 1 month and 2 months at ambient temperature + : stable emulsion 0 0 : slight trace of separation, emulsion homogeneous again after stirring 1 : incipient separation, flocculation and/or sedimen-tation - : distinct separation, emulsion irreversibly broken Accordingly, it can be seen that the addition of a quantity of 0.21% lecithin with a PC:PE ratio of 4.8:1 is nvt sufficient to obtain an emulsion which remains stable after storage for one or two months. The addi-tion of a quantity of 0.4% of a lecithin having a PC:PEratio of 4.8:1 is sufficient to keep the emulsion stable fo~ at least one month.
A nutritive composition is then prepared. An aqueous solution containing amino acids, namely L-leucine, glycine, L-alanine and L-proline, in a total ,, : .' 2 ~
quantity of 6.0 g in 75 ml water is initially prepared.
81 g of this aqueous solution are added to 19 g of the emulsion prepared as described above. The nutritive composition obtained i5 sterilized for 1 minute at 1~6C.
The osmolality and pH of the nutritive composi-tion before and after sterilization are determined. The stability of the composition is also visually observed.
The following xesults are obtained:
Dl D2 D3 D4 D5 D6 % 0.24 0.20 0.16 0.12 0.08 0.04 osmo 1 797 780 627 747 746 761 pH 1 8.06 8.08 8.05 8.22 8030 8.29 Osmo 2 751 779 625 750 758 758 pH 2 8.01 8.07 8.00 8.31 8.30 8.26 T0 ~ + + + + o Tl 0 0 0 % : percentage of lecithin in the final nutritive composition Osmo 1 : osmolality before sterilization (in mOsm/kg) Osmo 2 : osmolality after sterilization ~in mOsm/kg) 25 pH l/pH 2 : pH before/after sterilization T0 : observation just after preparation of the composition Tl/T2 : observation after storage for 1 month and 2 months at ambient temperature + : stable nutritive composition 0 : slight trace of separation, emulsion homogeneous again after stirring 1 : incipient separation, flocculation and/or ~edimen-.. . ; ..
' - , :'. .' .' - -.
.. . ~ . .
. .
tf~ t? i~
tation - : distinct separation, emulsion irreversibly broken The addition of a quantity of 0~04% lecithin with a 5 PC:PE ratio of 4.8:1 is not sufficient to obtain a stable nutritive composition. The addition of a ~uan-tity of 0.12~ lecithin with a PC:PE ratio of 4.8:1 is sufficient to obtain a stable nutritive composition containing 20% lipids and also amino acids.
Example 3 An aqueous phase is prepared by mixing 14.6 ml water, 0.4 ml glycerol and an emulsifying compound with a PC:PE ratio in the concentrations defined in the 15 following Table with stirring at 45C. 3.8 g of a soybean oil are then slowly added to this aqueous phase with continuous stirring, the temperature being kept at approximately 45C. An emulsion containing 20% lipids is thus obtained and is homogenized in the same way as 20 before. The pH of the emulsion thus prepared is ad-justed to 7.4 with 0.5N sodium hydroxide.
A nutritive composition is then prepared. An aqueous solution containing amino acids, namely L-leucine, glycine, L-alanine and L-proline, in a total 25 quantity of 6.0 g in 75 ml water is initially prepared.
81 g of this aqueous solution are added to 19 g of the emulsion prepared as described above. The nutriti~e composition obtained is sterilized for 1 minute at 126C.
The osmolality and pH of the nutritive composi-tion before and after sterilization are determined. The stability of the composition is also visually observed.
. - . ~ : . . ~, : ,. . . . . . .
. ,, . ~ . ~ , .
2~a~ 3."`~
The following results are ~btained:
Remarks ~ PC/PE Osmo 1 osmo 2 pH 1 p~ 2 T0 T1 T~ SI
0.16 2.5/1 709 711 7.92 7.88 + 1 87 0.04 4.1/1 746 745 8.35 8.33 0 - -.08 " 755 758 8.25 8.21 + 1 - 72 0.12 " 752 751 8.16 8.02 + 1 1 92 0.16 " 611 614 8.08 7.99 + 0 0 95 0.20 " 784 789 8.09 8.09 + 0 0 96 :
0.24 " 754 757 8.01 8.07 ~ 0 0 0.04 4.8/l 761 758 8.29 8.26 0 - -0.08 " 746 749 8.30 8.30 + - - ;
0.12 " 747 750 8.22 8.31 + 1 1 89 0.16 " 627 625 8.05 8.00 + 0 l 90 0.20 " 780 779 8.03 8.07 ~ 0 1 93 0.24 " 797 751 8.06 8.01 + 0 0 0.16 6.0/1 709 709 8.02 7.82 + 1 87 0.16 8.0/1 697 698 7.91 7.80 + 1 87 0.04 10.8/1 705 701 8.00 7.89 0.08 " 694 697 8.06 8.03 0 0.12 " 702 699 8.03 7.99 0 - 34 0.16 " 679 680 8.08 8.03 + - 34 0.20 " 684 676 7.80 7.92 + - 24 0.24 " 737 736 8.1~ 7.92 ~ -% : percentage of lecithin in the ~inal nutri-tive composition PC/PE : PC:PE ratio of the emulsifying compound .
Osmo 1 : osmolality before sterilization (in mOsm/kg) Osmo 2 : osmolality after sterilization (in mOsm/kg) . . . .:
- . : .
,, : - . :
.
' 2~O~?!~
pH 1/pH 2 : pH before/after sterilization T0 : observation just after preparation o~ the final nutritive composition T1/T2 : observation after storage for 1 month and 2 months at ambient temperature + : stable nutritive composition 0 : slight trace of separation, composition homogeneous again after stirring 1 : incipient separation, 1Occulation and/or sedimen-tation - : distinct separation, emulsion irreversibly broken SI O stability index Accordingly, it can be seen that a quantity of 0.08% emulsifying compound is sufficient to keep a nutritive composition containinq 20% lipids and having a dry matter content of approximately 10% stable provid-ing the emulis~ying compound has a PC:PE ratio o 2 to 10~
,, ~ .
Example 4 An aqueous phase is prepared by mixing 14.6 ml water, 0.4 ml glycerol and an emulsifying compound with a PC:PE ratio in the concentrations defined in the following Table with stirring at 45C. 3.8 g of a soybean oil are then slowly added to this aqueous phase with continuous stirring, the temperature being kept at approximately 45C. An emulsion containing 20% lipids is thus obtained and is homogenized in the same way as before. The pH of the emulsion thus prepared is ad-justed to 7.~ with 0.5N sodium hydroxide.
A nutritive composition is then prepared. An aqueous solution containing amino acids, namely L-`. :"
, :' '~:
,,, , ,, ., . , ~ , .
,.
' 17 leucine, glycine, L-alanine and L-proline, in a total quantity of 6.0 g in 75 ml water is initially prepared~
~1 g of this aqueous solution are added to 19 g of the emulsion prepared as described above, The nutritive composition obtained is sterilized for 1 minute at 12~C.
The stability index of the various nutritive compositions is determined as a function of the storage time.
The ~ollowing results are obtained:
Stability index SI (%) % PC/PE T0 ~1 T2 T3 0.08 4.1 76 73 77 76 0.12 4.8 94 87 86 84 0.20 4.8 85 85 85 83 0O20 10.8 55 54 54 56 % : percentage of emulsifying compound in the final nutritive composition It can be seen that these nutritive compositions have a relatively constant and. high stability index which means that they remain stable for at least 3 months.
Example 5 ~n aqueous phase is prepared by mixing 14.6 ml water, 0.4 ml glycerol and an emulsifying compound,with a PC:PE ratio as defined in the following Table in a concentration of 0.16% in the final composition ~0.83%
in the emulsion) with stirring at 45C. 3.8 g of a soybean oil are then slowly added to this aqueous phase with continuous stirring, the temperature being kept at .... . . . .
~;'' ' ' ' ~, ' , ', '.
- 2 1 0~~tf3 approximately ~5C. An emulsion containing 20% lipids is thus obtained and is homogenized in the same way as before. The pH of the emulsion thus prepared is ad-justed to 7.4 with 0.5N sodium hydroxide.
A nutritive composition is then prepared. An aqueous solution containing amino acids, namely L- -leucine, glycine, L-alanine and L-proline, in a total quantity of 6.0 g in 75 ml water is initially prepared.
81 g of this aqueous solution are added to 19 g of the ~0 emulsion prepared as described above. The nutritive composition obtained is sterilized for 1 minute at 126C.
The stability index of the various nutritive compositions obtained is determined.
The following results are obtained:
Total lipids SI
PC/PE % %
0.5 4.2 25 2.5 4.5 87 4.1 4.
4.8 4.2 90 6.0 3.9 87 8.0 3.9 87 ;
10.8 401 34 ~he stability index SI is determined after ;~
centrifugation for 15 minutes at 2000 r.p.m.
The stability index is relatively high except for the compositions containing an emulsifying compound with a PC:PE ratio that is not between 2 and 10:1. ;~
"
, .
, ~
. - ~
- a first sample of the prepared composition is removed and its fats content T1 is determined, - a second sample is removed and centrifuged for 15 minutes at 1000 r.p.m~/25C; this yenerally results in separation into two more or less distinct phases; ,~ '' - the fats content T2 of the 'lower phase of the centrifuged sample is determined and - the stability index SI (in %) is obtained by ~, establishing the ratio: T 2 x 100 4) Preparation of the PC/PE compounds Some of the emulsifying compounds used in the following Examples were prepared as follows:
- a quantity Ql of lecithin with a PC:PE ratio of 4 :1 is weighed and dissolved in 100 ml of a 2:1 mixture of dichloromethane and methanol, - a quantity Q2 of lecithin with a PC:PE ratio of 10:8 (or a quantity Q3 of pure PE3 is added and the whole is thoroughly mixed, - the solvent is evaporated to dryness, ~' - 100 ml water are added and the product obtained is redispersed with stirring and then freeze-dried.
., . . ~
; ~ ' " -2 1 o ~ ~ ? n Quantities to be added for the various PC:PE mixtures:
PC:PE 2.5.1 6:1 8:1 Q1 1 ~2 g 1 g ~2 1.832 g 3.223 g Q3 0.125 g Example An aqueous phase is prepared by mixing 14.6 ml ~0 water, 0.4 ml glycerol and egg lecithin with a PC:P~
ratio of 4.1:1 in the quantity defined in the following Table with stirring at 45C. 3.8 g of a soybean oil are then slowly added to this aqueous phase with continuous stirring, the temperature being kept at approximately 45~.
An emulsion containing 20~ lipids is obtained in this way and is subsequently homogenized after five pas- ~-sages through a suitable apparatus of the "Microfluid-izer" type under a pressure of 1100 bar and at a temper-ature of 20C to 50C in order to obtain an average droplet size in the lipid phase of 250 to 950 nm. The pH of the emulsion thus prepared is ad~usted to 7.4 with 0.5 N sodium hydroxide, after which the emulsion is packed in 100 ml bottles which are sterilized for 9 minutes at 126C.
The osmolality and the pH of the emulsion are determined before and after sterilization. The stabil-ity of the emulsion is also Yisually observed.
The following results are obtained:
Al A2 A3 A4 A5 A6 % 1.28 1.05 0.83 0.62 0.41 0.21 Osmo 1 342 346 351 327 353 327 pH 1 3.87 3.99 4017 4.67 5.06 5.82 Osmo 2 343 349 353 325 353 328 ~.
2 i ~ 3~
Al A2 A3 A4 A5 A6 pH 2 ~.76 5. ns 5.08 5.3~ 5.29 5.23 T0 -~ t + ~ +
T1 + ~ +
T2 +
~ : percentage of lecithin in the emulsion Osmo 1 : osmolality before sterilization (in mOsm/kg) pH 1 : pH before sterilization Osmo 2 : osmolality after sterilization (in mOsm/kg) pH 2 : pH after sterilization T0 : observation just after prepara~ion of th emulsion Tl : observation after storage for 1 month at ambient temperature T2 : observation after storage for 2 months at ambient temperature + : stable emulsion 0 : slight trace of separation, emulsion homogeneous again after stirring 1 : incipient separation, flocculation and/or sedimen-tation - : distinct separation, emulsion irreversibly broken Accordingly, it can be selen that the addition of a quantity of 0.21% lecithin with a PC:PE ratio of 4.1~il is not sufficient to obtain an emulsion which remains stable after storage for one or two monthsO The addi- .-tion of a quantity of 0.4% of a lecithin having a PC:PE
ratio of 4.1:1 is sufficient to keep the emulsion stable for at least two months.
A nutritive composition is then prepared. An aqueous solution containing amino acids, namely L
leucine, glycine, L-alanine and L-proline, in a total ,. . . .,, , , . . - . . :. ~ .: . : :i ~ :
:: , :
:. . - . .
: , , - .:: ~.:. . :
2 ~
quantity of 6.0 g in 75 ml water is initially prepared.
81 g of this aqueous solution are added to l9 g of the emulsion prepared as described above. The nutritive composition obtained is sterilized for 1 minute at 126C.
The osmolality and pH of the nutritive composi-tion before and after sterilization are determined. The stability of the composition is also visually observed.
The following results are obtained:
Bl B2 B3 B4 B5 B6 % 0.2~ 0.20 0.16 0.12 0.08 0.04 Osmo 1 753 784 611 752 755 746 pH 1 8.01 8.09 8.08 8.16 8.25 8.35 Osmo 2 756 789 614 752 758 744 pH 2 8.07 8.09 7.99 8.02 8.21 8.33 T0 ~ + + + + o T2 o 0 0 % : percentage of lecithin in the final nutritive composition Osmo 1 : osmolality before stlerilization (in mOsm/kg) Osmo 2 : osmolality after sterilization (in mOsm/kg) 25 pH l/pH 2 : pH before/after sterilization T0 : observation just after preparation of the composition Tl/T2 : observation after storage for 1 month and 2 months at ambient temperature + : stable nutritive composition 0 : slight trace of separation, emulsion homogen~ous again after stirring l : incipient separation, flocculation and/or sedimen-~':
-.............................. . . ~ -:
.: . . - : .. : -- .
. .. .... . .
. ~
~, , '.,:: ~ .
21~'~9 3~
tation - : distinct separation, emulsion irreversibly broken Accordingly, it can be seen that the addition of a quantity of 0.04% lecithin with a PC:PE ratio of 4.1:1 is not sufficient to obtain a stable nutritive composi tion. The addition of a quantity of 0.08% lecithin with a PC:PE ratio of 4.1:1 is sufficient to obtain a stable nutritive composition containing 20% lipids and also amino acids, but not to keep it stable during storage for several months.
Ex~mple 2 An aqueous phase is prepared by mixing 14.6 ml water, 0.4 ml glycerol and egg lecithin with a PC:PE
ratio of 4.8:1 in the quantity defined in the following Table with stirring at 4~C. 3.8 g of a soybean oil are slowly added to the aqueous phase thus prepared with continuous stirring, the temperature being kept at approximately 45C. An emulsion containing 20~ lipids is obtained in this way and is homogenized in the same way as before to obtain an average droplet size in the lipid phase of 250 to ~50 nm. The pH of the emulsion thus prepared is adjusted to 7.4 with 0.5 N sodium hydroxide solution, after which the emulsion is packed in 100 ml bottles which are sterilized for 9 minutes at 126C.
The osmolality and pH of the emulsion are deter-mined before and after sterilization. The stability of the emulsion is also visually observed: ~
The following results are obtainedo Cl C2 C3 C4 C5 C6 % 1.28 1.05 0.83 0.62 0.41 0.21 Osmo 1 333 321 331 341 341 376 . ~
, - -; :
.
. ' ' ' .
- : ., : . . , 2 ~ 3 t3 f~
C1 C2 C3 C~ C5 C6 p~ 1 ~.26 ~.58 ~.59 5.18 5.05 6.20 Osmo 2 331 325 333 342 339 377 pH 2 5.33 5.68 6.02 5.41 5.52 5.30 T0 + + + ~ + o Tl + + -~ + -~ -T2 + + + 1 - -% : percentage of lecithin in the emulsion Osmo 1 : osmolality before sterilization (in mOsm/kg) Osmo 2 : osmolality after sterilization (in mOsm/kg) pH l/p~ 2 : pH before/after sterilization TO : observation just after preparation of the emulsion Tl/T2 : observation after storage for 1 month and 2 months at ambient temperature + : stable emulsion 0 0 : slight trace of separation, emulsion homogeneous again after stirring 1 : incipient separation, flocculation and/or sedimen-tation - : distinct separation, emulsion irreversibly broken Accordingly, it can be seen that the addition of a quantity of 0.21% lecithin with a PC:PE ratio of 4.8:1 is nvt sufficient to obtain an emulsion which remains stable after storage for one or two months. The addi-tion of a quantity of 0.4% of a lecithin having a PC:PEratio of 4.8:1 is sufficient to keep the emulsion stable fo~ at least one month.
A nutritive composition is then prepared. An aqueous solution containing amino acids, namely L-leucine, glycine, L-alanine and L-proline, in a total ,, : .' 2 ~
quantity of 6.0 g in 75 ml water is initially prepared.
81 g of this aqueous solution are added to 19 g of the emulsion prepared as described above. The nutritive composition obtained i5 sterilized for 1 minute at 1~6C.
The osmolality and pH of the nutritive composi-tion before and after sterilization are determined. The stability of the composition is also visually observed.
The following xesults are obtained:
Dl D2 D3 D4 D5 D6 % 0.24 0.20 0.16 0.12 0.08 0.04 osmo 1 797 780 627 747 746 761 pH 1 8.06 8.08 8.05 8.22 8030 8.29 Osmo 2 751 779 625 750 758 758 pH 2 8.01 8.07 8.00 8.31 8.30 8.26 T0 ~ + + + + o Tl 0 0 0 % : percentage of lecithin in the final nutritive composition Osmo 1 : osmolality before sterilization (in mOsm/kg) Osmo 2 : osmolality after sterilization ~in mOsm/kg) 25 pH l/pH 2 : pH before/after sterilization T0 : observation just after preparation of the composition Tl/T2 : observation after storage for 1 month and 2 months at ambient temperature + : stable nutritive composition 0 : slight trace of separation, emulsion homogeneous again after stirring 1 : incipient separation, flocculation and/or ~edimen-.. . ; ..
' - , :'. .' .' - -.
.. . ~ . .
. .
tf~ t? i~
tation - : distinct separation, emulsion irreversibly broken The addition of a quantity of 0~04% lecithin with a 5 PC:PE ratio of 4.8:1 is not sufficient to obtain a stable nutritive composition. The addition of a ~uan-tity of 0.12~ lecithin with a PC:PE ratio of 4.8:1 is sufficient to obtain a stable nutritive composition containing 20% lipids and also amino acids.
Example 3 An aqueous phase is prepared by mixing 14.6 ml water, 0.4 ml glycerol and an emulsifying compound with a PC:PE ratio in the concentrations defined in the 15 following Table with stirring at 45C. 3.8 g of a soybean oil are then slowly added to this aqueous phase with continuous stirring, the temperature being kept at approximately 45C. An emulsion containing 20% lipids is thus obtained and is homogenized in the same way as 20 before. The pH of the emulsion thus prepared is ad-justed to 7.4 with 0.5N sodium hydroxide.
A nutritive composition is then prepared. An aqueous solution containing amino acids, namely L-leucine, glycine, L-alanine and L-proline, in a total 25 quantity of 6.0 g in 75 ml water is initially prepared.
81 g of this aqueous solution are added to 19 g of the emulsion prepared as described above. The nutriti~e composition obtained is sterilized for 1 minute at 126C.
The osmolality and pH of the nutritive composi-tion before and after sterilization are determined. The stability of the composition is also visually observed.
. - . ~ : . . ~, : ,. . . . . . .
. ,, . ~ . ~ , .
2~a~ 3."`~
The following results are ~btained:
Remarks ~ PC/PE Osmo 1 osmo 2 pH 1 p~ 2 T0 T1 T~ SI
0.16 2.5/1 709 711 7.92 7.88 + 1 87 0.04 4.1/1 746 745 8.35 8.33 0 - -.08 " 755 758 8.25 8.21 + 1 - 72 0.12 " 752 751 8.16 8.02 + 1 1 92 0.16 " 611 614 8.08 7.99 + 0 0 95 0.20 " 784 789 8.09 8.09 + 0 0 96 :
0.24 " 754 757 8.01 8.07 ~ 0 0 0.04 4.8/l 761 758 8.29 8.26 0 - -0.08 " 746 749 8.30 8.30 + - - ;
0.12 " 747 750 8.22 8.31 + 1 1 89 0.16 " 627 625 8.05 8.00 + 0 l 90 0.20 " 780 779 8.03 8.07 ~ 0 1 93 0.24 " 797 751 8.06 8.01 + 0 0 0.16 6.0/1 709 709 8.02 7.82 + 1 87 0.16 8.0/1 697 698 7.91 7.80 + 1 87 0.04 10.8/1 705 701 8.00 7.89 0.08 " 694 697 8.06 8.03 0 0.12 " 702 699 8.03 7.99 0 - 34 0.16 " 679 680 8.08 8.03 + - 34 0.20 " 684 676 7.80 7.92 + - 24 0.24 " 737 736 8.1~ 7.92 ~ -% : percentage of lecithin in the ~inal nutri-tive composition PC/PE : PC:PE ratio of the emulsifying compound .
Osmo 1 : osmolality before sterilization (in mOsm/kg) Osmo 2 : osmolality after sterilization (in mOsm/kg) . . . .:
- . : .
,, : - . :
.
' 2~O~?!~
pH 1/pH 2 : pH before/after sterilization T0 : observation just after preparation o~ the final nutritive composition T1/T2 : observation after storage for 1 month and 2 months at ambient temperature + : stable nutritive composition 0 : slight trace of separation, composition homogeneous again after stirring 1 : incipient separation, 1Occulation and/or sedimen-tation - : distinct separation, emulsion irreversibly broken SI O stability index Accordingly, it can be seen that a quantity of 0.08% emulsifying compound is sufficient to keep a nutritive composition containinq 20% lipids and having a dry matter content of approximately 10% stable provid-ing the emulis~ying compound has a PC:PE ratio o 2 to 10~
,, ~ .
Example 4 An aqueous phase is prepared by mixing 14.6 ml water, 0.4 ml glycerol and an emulsifying compound with a PC:PE ratio in the concentrations defined in the following Table with stirring at 45C. 3.8 g of a soybean oil are then slowly added to this aqueous phase with continuous stirring, the temperature being kept at approximately 45C. An emulsion containing 20% lipids is thus obtained and is homogenized in the same way as before. The pH of the emulsion thus prepared is ad-justed to 7.~ with 0.5N sodium hydroxide.
A nutritive composition is then prepared. An aqueous solution containing amino acids, namely L-`. :"
, :' '~:
,,, , ,, ., . , ~ , .
,.
' 17 leucine, glycine, L-alanine and L-proline, in a total quantity of 6.0 g in 75 ml water is initially prepared~
~1 g of this aqueous solution are added to 19 g of the emulsion prepared as described above, The nutritive composition obtained is sterilized for 1 minute at 12~C.
The stability index of the various nutritive compositions is determined as a function of the storage time.
The ~ollowing results are obtained:
Stability index SI (%) % PC/PE T0 ~1 T2 T3 0.08 4.1 76 73 77 76 0.12 4.8 94 87 86 84 0.20 4.8 85 85 85 83 0O20 10.8 55 54 54 56 % : percentage of emulsifying compound in the final nutritive composition It can be seen that these nutritive compositions have a relatively constant and. high stability index which means that they remain stable for at least 3 months.
Example 5 ~n aqueous phase is prepared by mixing 14.6 ml water, 0.4 ml glycerol and an emulsifying compound,with a PC:PE ratio as defined in the following Table in a concentration of 0.16% in the final composition ~0.83%
in the emulsion) with stirring at 45C. 3.8 g of a soybean oil are then slowly added to this aqueous phase with continuous stirring, the temperature being kept at .... . . . .
~;'' ' ' ' ~, ' , ', '.
- 2 1 0~~tf3 approximately ~5C. An emulsion containing 20% lipids is thus obtained and is homogenized in the same way as before. The pH of the emulsion thus prepared is ad-justed to 7.4 with 0.5N sodium hydroxide.
A nutritive composition is then prepared. An aqueous solution containing amino acids, namely L- -leucine, glycine, L-alanine and L-proline, in a total quantity of 6.0 g in 75 ml water is initially prepared.
81 g of this aqueous solution are added to 19 g of the ~0 emulsion prepared as described above. The nutritive composition obtained is sterilized for 1 minute at 126C.
The stability index of the various nutritive compositions obtained is determined.
The following results are obtained:
Total lipids SI
PC/PE % %
0.5 4.2 25 2.5 4.5 87 4.1 4.
4.8 4.2 90 6.0 3.9 87 8.0 3.9 87 ;
10.8 401 34 ~he stability index SI is determined after ;~
centrifugation for 15 minutes at 2000 r.p.m.
The stability index is relatively high except for the compositions containing an emulsifying compound with a PC:PE ratio that is not between 2 and 10:1. ;~
"
, .
, ~
. - ~
Claims (5)
1. A composition in the form of an oil-in-water emulsion containing at least 10% by weight lipids and at least 0.4% by weight of an emulsifying compound compri-sing phosphatidyl choline (PC) and phosphatidyl ethanol-amine (PE) in a ratio of PC to PE of 2 to 10:1.
2. A nutritive composition containing 1 part by weight of the composition claimed in claim 1 and 0 to 15 parts water optionally containing an amino acid source.
3. A process for the production of a composition in the form of an oil-in-water emulsion, in which an aqueous phase and a lipid phase are prepared, at least 0.4% of an emulsifying compound comprising phosphatidyl choline (PC) and phosphatidyl ethanolamine (PE) in a ratio of PC to PE of 2 to 10:1 is added to one and/or the other of the phases, the two resulting phases are mixed to form an emulsion containing at least 10% by weight lipids and the emulsion obtained is sterilized.
4. A process as claimed in claim 3, in which 0 to 15 parts water optionally containing an amino acid source are added to 1 part by weight of the emulsion before or after its sterilization, after which the nutritive composition thus obtained is sterilized.
5. The use of the compositions claimed in claims 1 and 2 for parenteral feeding.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH2735/92-1 | 1992-09-01 | ||
CH273592 | 1992-09-01 |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2104930A1 true CA2104930A1 (en) | 1994-03-02 |
Family
ID=4240433
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002104930A Abandoned CA2104930A1 (en) | 1992-09-01 | 1993-08-26 | Nutritive composition and a process for its preparation |
Country Status (8)
Country | Link |
---|---|
EP (1) | EP0598989A1 (en) |
JP (1) | JPH06172206A (en) |
KR (1) | KR940006488A (en) |
CN (1) | CN1086102A (en) |
AU (1) | AU4461993A (en) |
CA (1) | CA2104930A1 (en) |
FI (1) | FI933798A (en) |
NO (1) | NO933076L (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002068998A (en) * | 2000-08-29 | 2002-03-08 | Meiji Milk Prod Co Ltd | Composition for preventing occurrence of fatty liver accompanied by transintestine nutrition and intraveneous nutrition |
MXPA03008975A (en) * | 2001-04-03 | 2004-02-17 | Bristol Myers Squibb Pharma Co | Stabilization and terminal sterilization of phospholipid formulations. |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2948607A1 (en) * | 1979-12-03 | 1981-06-11 | Chemische Fabrik Dr. Meyer-Castens & Co Nfg., 2000 Hamburg | METHOD FOR PRODUCING A LECITHIN-BASED EMULSIFIER |
FR2540119B1 (en) * | 1983-02-01 | 1986-10-17 | Synthelabo | PHOSPHATIDE FRACTIONATION PROCESS |
US4563354A (en) * | 1983-10-26 | 1986-01-07 | Kabivitrum Ab | Oil-in-water emulsion for parenteral administration |
EP0313617B1 (en) * | 1987-04-22 | 1992-08-12 | BAXTER INTERNATIONAL INC. (a Delaware corporation) | Lipid emulsion and method for intravenous infusion |
AU612149B2 (en) * | 1987-05-01 | 1991-07-04 | Otsuka Pharmaceutical Co., Ltd. | Nutritive emulsion preparation |
-
1993
- 1993-08-03 EP EP93112386A patent/EP0598989A1/en not_active Withdrawn
- 1993-08-12 AU AU44619/93A patent/AU4461993A/en not_active Abandoned
- 1993-08-26 CA CA002104930A patent/CA2104930A1/en not_active Abandoned
- 1993-08-30 NO NO933076A patent/NO933076L/en unknown
- 1993-08-31 JP JP5216299A patent/JPH06172206A/en not_active Withdrawn
- 1993-08-31 KR KR1019930017238A patent/KR940006488A/en not_active Application Discontinuation
- 1993-08-31 FI FI933798A patent/FI933798A/en not_active Application Discontinuation
- 1993-09-01 CN CN93116436A patent/CN1086102A/en active Pending
Also Published As
Publication number | Publication date |
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KR940006488A (en) | 1994-04-25 |
EP0598989A1 (en) | 1994-06-01 |
FI933798A (en) | 1994-03-02 |
JPH06172206A (en) | 1994-06-21 |
CN1086102A (en) | 1994-05-04 |
NO933076L (en) | 1994-03-02 |
NO933076D0 (en) | 1993-08-30 |
FI933798A0 (en) | 1993-08-31 |
AU4461993A (en) | 1994-03-10 |
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