WO2008002116A1 - Formulation of argan oil-based lipid emulsion for parenteral nutrition - Google Patents

Abstract

The purpose of the present invention is to introduce argan oil for the first time into preparations for enteral and parenteral nutrition. Parental nutrition preparations take the form of argan oil-based, injectable lipid emulsions. Enteral nutrition preparations take the form of mixtures that are mixed or not mixed with polymeric or monomeric nutrients of food components: that is, glucids, lipids, protids, trace elements, and water incorporating argan oil as a lipid component. Justification for using argan lipids in enteral and parenteral nutrition lies mainly in the fact that argan lipids provide essential fatty acids that the organism itself is not capable of synthesizing in the same manner as other oils utilized in this field, but in a proportion and combination very specific to it. This compositional specificity in fatty acids gives argan oil qualities that merit widespread use for nutrition purposes in the medical field. Thus, the distinctive feature of this invention is its use, for the first time, of a traditional oil, argan oil, as a component of enteral and parenteral preparations. Parenteral nutrition is indispensable as compensation for nutritional deficiencies accompanying many diseases. It has undergone major development with the manufacture of patient-specific and ready-made parenteral nutrition bags. Lipid emulsions for parenteral nutrition currently on the market are soy oil-based and olive oil-based. Vegetable oils are known for their content of fatty acids, an important energy source playing a structural role in the cell membrane to ensure fluidity and neurotransmission. Argan oil, due to its exceptional unsaturated fatty acid composition, combines the fatty acid composition of olive oil, with its important monounsaturated fatty acid content, especially oleic acid, and the fatty acid composition of soy oil, with its polyunsaturated fatty acid content, especially linoleic acid (omega 6) and linolenic acid (omega 3). The latter and their metabolites are indispensable fatty acids for normal growth and for the physiological functions of all tissues but are not synthesized by the organism itself. The dietary contribution of argan oil no longer requires proof. Parenteral administration for diseases is an entirely worthwhile endeavor. Unsaturated fatty acids of argan oil regulate cholesterol rate, especially the omega 6 [fatty acids] that are indispensable to the growth of children and the regeneration of skin tissue. For all these reasons, we have considered parenterally administering argan oil in an aqueous emulsion form for use on certain diseases. Formulating an oil-type lipid emulsion in argan oil-based water is delicate. The stable formula that has been obtained is not far removed from formulas for other emulsions on the market.

Description

 Formulation of a lipid emulsion based on argan oil for parenteral nutrition

INTRODUCTION:

Parenteral nutrition has made considerable progress since the first venous passage of 2 liters of 10% glucose solute supplemented with Na, K and vitamin B.

Today we know how to achieve parenteral nutrition very suitable for each patient to ensure a perfect nutritional situation.

Parenteral nutrition is the last resort in the patient after enteral nutrition, it is used in many digestive diseases: acute esophagitis, gastric disease type Zollinger-Ellison syndrome, pancreatitis or pancreatic fistula, hail disease or Crohn's disease and finally some digestive neoplasias. It must be complete, that is to say include carbohydrates, amino acids, lipids, electrolytes, vitamins and trace elements.

The lipids provided by parenteral nutrition represent 35 to 40% of the total caloric intake. The lipid emulsions currently used are based on soybean oil and olive oil and are used especially when it is necessary to provide a considerable calorie intake.

Vegetable oils are the most used in parenteral nutrition for their unsaturated fatty acid content, especially in essential fatty acids.

The most important fatty acids are: monounsaturated fatty acid, oleic acid, which plays a major antioxidant role and intervenes by limiting the cellular oxidation process and the polyunsaturated fatty acids including essential fatty acids. linoleic acid and linolenic acid. Linoleic acid plays a role in the constitution of cell membranes. Linolenic acid, on the other hand, provides an essential function for the structure of nerve cells.

The idea of using argan oil in parenteral nutrition in some specific patients is fully justified. First for to valorize the products of the soil and then for the particular content in unsaturated fatty acids.

Argan oil has many virtues. It is used in food for seasoning thanks to its nutty taste and in dietetics for its hypolipidemic and antihypertensive properties due to the polyunsaturated fatty acids it contains. It is also used in cosmetology in body and hair care products, for its high content of tocopherols known to be an antioxidant cells delaying their aging.

Argan oil has a composition of the most balanced. It has a unique combination of unsaturated fatty acids with 50% mono-unsaturated fatty acids including oleic acid and more than 30% polyunsaturated fatty acids including linoleic acid from the omega 6 family.

Fatty acids are an important source of energy and especially omega 6 fatty acids are essential for the growth of the child, the regeneration of skin tissues and the mediation of nerve endings.

Argan oil is an important source of fatty acids. A deficiency of fatty acids can cause in the infant and the young child cutaneous disorders such as atopic dermatitis. Fatty acid deficiency in adults can lead to cardiovascular disorders.

Argan oil is an important source of essential fatty acids. A deficiency of essential fatty acids causes in humans a decrease in the growth rate, eczema, reproductive disorder, coagulation disorder, immune system disorder, reduction of prostaglandin biosynthesis and dehydration.

Sometimes, even if the intake of linoleic fatty acid is sufficient in the diet, it is possible that its metabolism is disrupted by an enzyme deficiency such as a too small amount of D 6 desaturase (metabolic enzyme). Vitamin deficiencies can cause abnormalities in the mechanism of D 6 desaturase, which is controlled by zinc and magnesium. In these cases, the administration of oils rich in essential fatty acids, such as argan oil, is important.

In some patients, the administration of argan oil can be of great benefit and can be done only parenterally. Our work presents a test of formulation of a sand lipid emulsion with argan oil base and then make pouches used in parenteral nutrition.

The benefit would not only be clinical but also economic. The pocket of the injectable lipid emulsion based on argan oil, produced locally, would be cheaper than the imported bags that are currently marketed.

MATERIAL AND METHOD :

-The oil of argane:

The argan oil we have chosen to study is pharmaceutical grade argan oil obtained by cold pressing of unroasted fines.

The argan oil we've been working on has been analyzed and found within the set standards. The following table shows the fatty acid and tocopherol composition of the argan oil used.

Table I: composition Argan oil

Fatty acids

les tocophérols :

tocopherols:

Egg lecithin or phosphatidylcholine is a nonionic surfactant more hydrophilic than lipophilic, it acts sterically hindered to reduce the interfacial tension between water and oil to bring them closer together. The emulsion is thus stabilized by the pure and injectable quality lecithin of egg corresponding to levels of nearly 92% of phosphatidylcholine.

-The formulation :

The basic formula we have worked on is, in general, that of injectable lipid emulsions:

Aqueous phase represents 60 to 99.9%

Eppi

Isotonizing: glycerol

Isophisant: soda

Tensio-active represents 0.5 to 2% (% taken from the aqueous phase) Egg lecithin +/- nonionic surfactant +/- Co-emulsifier: sodium oleate

Oily phase represents 0.1 to 40%

Argan oil

+/- antioxidant: alpha-tocopherol

In the formulation tests we integrated these compositions in ternary diagrams to have the most stable emulsion. The/\ Emulsion controls obtained are expressed as a score to facilitate evaluation.

-The protocol :

The protocol is that of a conventional emulsion with the preparation of the two phases separately and then mixing the two phases with stirring followed by ripening and then homogenization.

The checks carried out are:

-the colour

-the particle size

-meaning

-the pH

-the viscosity

stability: centrifugation and the temperature of the oven.

RESULTS:

The formulas with which we have worked are represented in the form of ternary diagrams and the proportions of the components of each emulsion are represented in the following table:

below an example of studied emulsions.

0.09 g

With the results of the controls expressed in the diagram below

= UNSTABLE EMULSION

= EMULSION STABLE A + de 6 mois= STABLE EMULSION Short term (<one month)

= STABLE EMULSION A + 6 months

The stability zone of the emulsion is on the left and bottom of the ternary diagram.

The formulas of the most stable emulsions taken into account are represented in the following table:

Argan oil 20g

Surfactant 1,2g to 2,4g

Glycerol o to 5g

Sodium oleate 0.015 to 0.045g

Water ppi QSP Iooml DISCUSSION:

The Argan tree, Argania spinosa L., family of sapotaceae, is a specifically Moroccan tree, protected by DAHIR and classified as a biosphere reserve by UNESCO. Argan oil is precious, it takes the production of 6 to 7 trees for 1 liter of oil!

The interest of using argan oil in dietetics is due to the presence of unsaturated fatty acids: more than 80% of unsaturated fatty acids and less than 20% of saturated fatty acids. Argan oil has superior nutritional and dietary properties to extra virgin olive oil that is less rich in polyunsaturated fatty acids. Monounsaturated fatty acid content of argan oil is more important than soybean oil. Table II shows that the fatty acid composition of argan oil is close to the composition of soybean oil and olive oil. Argan oil is recommended by nutritionists for its hypocholesterolemic and antiatherogenic action by the presence of mainly oleic acid and linoleic acid. Oleic acid has a regulatory role in the metabolism of lipids and cholesterol. The linoleic acid (omega 6) essential for life, plays an important role in the growth and physiological functions of all tissues (cardiac function, renal, skin ...). It is involved in the metabolism of prostaglandins and leukotrienes which controls inflammatory reactions and enters into the constitution of membrane lipids. Linoleic acid helps prevent cardiovascular disease by helping to lower cholesterol levels by turning cholesterol into fluid and preventing atherosclerosis.

Pour ses propriétés diététiques favorables, l'huile d'argane se révèle intéressante dans les carences nutritionnelles ou malnutrition protéino- énergétique surtout chez l'enfant. Sa richesse en acide oléique et acide linoléique lui confère une place intermédiaire entre l'huile de soja et l'huile d'argane. Dans le commerce, il existe des émulsions lipidiques injectables à base de l'huile de soja riche en acide linoléique et linolénique supplémenter d'huile d'olive pour l'apport de l'acide oléique. L'émulsion lipidique injectable à base d'huile d'argan sera non seulement une innovation sur le plan galénique mais aussi sur le plan clinique.

For its favorable dietary properties, argan oil is interesting in nutritional deficiencies or protein-energy malnutrition especially in children. Its richness in oleic acid and linoleic acid gives it an intermediate place between soybean oil and argan oil. In commerce, there are injectable lipid emulsions based on soybean oil rich in linoleic acid and linolenic supplement with olive oil for the supply of oleic acid. The injectable lipid emulsion based on argan oil will be not only an innovation in terms of galenic but also clinically.

The formula considered stable does not deviate from the basic formula and formulas already marketed based on soybean oil. The formulation of an emulsion is always difficult because the emulsion is a thermo dynamically unstable system. Our work will continue in the sense of optimizing working conditions to achieve stability over a longer period. A longer stability would be useful in practice for the sterilization, storage and then administration of the injectable lipid emulsion based on argan oil.

CONCLUSION:

Argan oil is used orally and cutaneously but never before injection. This oil has all the assets to expand its use to the clinic. This project is part of the development of argan oil, a product of the soil so precious.

In addition to dietary intake of argan oil, the economic gain would not be negligible since it involves using a Moroccan product in specific patients in our hospitals during their parenteral nutrition.

Claims

CLAIMS - Formulation of a lipid emulsion for parenteral nutrition characterized in that it contains argan oil in its lipophilic phase. Formulation of a lipid emulsion for parenteral nutrition, according to claim 1, characterized in that it contains pharmaceutically acceptable excipients and adapted for parenteral administration. - Pharmaceutical preparation according to claims 1 and 2, characterized in that the argan oil is used alone or in combination with other total or fractionated oils of natural origin (vegetable or animal), semi-synthetic or synthetic, - Preparation according to claims 1 and 3, characterized in that the lipid concentration is between 0, 1 and 40% by weight of the total preparation, - Use of a preparation according to one of claims 1 to 4 for the artificial feeding, enteral or parenteral.