Patent Publication Number: US-4368204-A

Title: Nutrition composition for pediatrics

Description:
BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates to a novel nutritional composition for pediatric use. 
     2. Description of the Prior Art 
     Elemental diet compositions, comprising amino acids, carbohydrates such as mono- and oligosaccharides, fats, vitamins, minerals, and additives such as preservatives and emulsifiers have been proposed for the nutrition of children in special circumstances. 
     However, currently available manufactured elemental diet compositions are not always suitable for children having various conditions or illnesses that normally call for the use of such compositions in adults. 
     For example, irregular or poor metabolism of amino acids can often occur in a child, particularly in a sick or weak child. In such cases, a nutritional composition that varies in the composition and concentration of amino acids present, as in known manufactured compositions, may be ineffective. Therefore, known manufactured compositions are sometimes unable to satisfy the nutritional requirements of children suffering from these conditions. 
     SUMMARY OF THE INVENTION 
     Accordingly, it is an object of this invention to provide an elemental nutritional composition that satisfies the nutritional requirements of children. 
     It is another object of the invention to provide an elemental nutritional composition having a balanced amino acid content suitable for the nutritional requirements of children. 
     These and other objects of the invention which will hereinafter become more readily apparent have been accomplished by providing a nutritional composition for pediatrics comprising amino acids wherein the following amino acids are present in the indicated amounts: 
     
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              % by Weight of Total                                        
Amino Acid    Amino Acids                                                 
______________________________________                                    
L-isoleucine  4.50 to 6.08                                                
L-leucine      8.70 to 11.78                                              
L-lysine      6.58 to 8.90                                                
L-methionine  1.38 to 1.86                                                
L-cysteine    1.87 to 2.53                                                
L-phenylalanine                                                           
              2.69 to 3.63                                                
L-tyrosine    3.79 to 5.13                                                
L-threonine   4.30 to 5.82                                                
L-tryptophan  1.62 to 2.19                                                
L-valine      4.65 to 6.29                                                
L-histidine   2.43 to 3.29                                                
L-alanine      8.32 to 11.26                                              
L-arginine    6.00 to 8.12                                                
L-aspartic acid                                                           
              3.62 to 4.90                                                
L-glutamic acid                                                           
              6.47 to 8.76                                                
glycine       1.96 to 2.66                                                
L-proline      8.46 to 11.44                                              
L-serine       7.66 to 10.36                                              
Total         100                                                         
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     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     The inventors have investigated the nutritional requirements of children up to about ten years of age, particularly from neonate to about six years of age, and have completed the present invention based on these findings. 
     As a result of these studies, the inventors have discovered that the nutritional requirements of children are provided for by a nutritional composition for pediatrics comprising amino acids wherein the following amino acids are present in the indicated amounts: 
     
         ______________________________________                                    
              % by Weight of Total                                        
Amino Acid    Amino Acids                                                 
______________________________________                                    
L-isoleucine  4.50 to 6.08                                                
L-leucine      8.70 to 11.78                                              
L-lysine      6.58 to 8.90                                                
L-methionine  1.38 to 1.86                                                
L-cysteine    1.87 to 2.53                                                
L-phenylalanine                                                           
              2.69 to 3.63                                                
L-tyrosine    3.79 to 5.13                                                
L-threonine   4.30 to 5.82                                                
L-tryptophan  1.62 to 2.19                                                
L valine      4.65 to 6.29                                                
L-histidine   2.43 to 3.29                                                
L-alanine      8.32 to 11.26                                              
L-arginine    6.00 to 8.12                                                
L-aspartic acid                                                           
              3.62 to 4.90                                                
L-glutamic acid                                                           
              6.47 to 8.76                                                
glycine       1.96 to 2.66                                                
L-proline      8.46 to 11.44                                              
L-serine       7.66 to 10.36                                              
Total         100                                                         
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     In the composition listed above, values for weights of the above-mentioned amino acids are indicated in the free form. However, derivatives or adducts of amino acids which can be metabolized to amino acids in the human body can also be used. 
     For example, suitable derivatives of amino acids include amine salts with mineral acids, such as hydrochloric acid, or organic acids; carboxylic acid metal salts, such as sodium, potassium, calcium, and magnesium salts; peptides; N-acylated amino acids; and hydrates. For example, amino acids such as lysine, cysteine, histidine, and arginine can be used in the form of a hydrochloric or acetic acid salt. Tyrosine can be used as the ethyl ester hydrochloride or N-acetylated derivative, and aspartic acid can be used as a metal salt, such as a potassium or magnesium salt. 
     When derivatives of amino acids are used, the required weight of each derivative can be easily calculated from the molecular weights of the derivative and the free forms as is well known in the art. 
     The total amino acid content in the composition of the present invention may be from about 5 to about 20% of the total weight of the composition. 
     Various combinations of additional ingredients may be used in the composition of the invention along with the indicated amounts of amino acids. For example, dextrin may be employed as the carbohydrate. Mono- and oligosaccharides may also be employed. The carbohydrate content of the composition is usually about 75 to 85%, but can be higher, if necessary. 
     Various plant oils, such as corn, soybean, and cotton seed oil, can be employed as fats with the present invention. When a low amount of fat, for example, about 2 to 4% by weight, is used, the solubility and emulsifiability of the composition are improved, and the occurrence of diarrhea in patients sensitive to fats is lessened. 
     Vitamins in many forms are also suitable for use in the present invention. Some examples include vitamin A as retinole acetate, vitamin B 1  as thiamine hydrochloride, vitamin B 2  as riboflavine sodium phosphate, vitamin B 6  is pyridoxine hydrochloride, vitamin B 12  as cyanocobalamin, vitamin C as ascorbic acid, vitamin D 2  as ergocalciferol, vitamin E as tocopherol acetate, and vitamin K 1  as phytonadione. Also suitable are calcium pantothenic acid, nicotinamide, biotin, folic acid, and choline bitartarate, among others. 
     Generally, about 50 to 100 mg of vitamins are present in 80 g of the nutritional composition, and as such, the concentration of vitamins is about 0.1% by weight. 
     Particularly useful are compositions containing vitamin C and vitamin D 2  in amounts greater than the amounts presently used in elemental diets in view of the growth requirements of children. For example, about 20 to 40 mg of ascorbic acid or about 5 to 15 μg of ergocalciferol is desirably employed per 80 g of the nutritional composition. 
     Minerals may also be employed in the nutritional composition. Minerals in suitable form include iron as gluconic acid iron salt dihydrate, copper as cupric sulfate pentahydrate, manganese as manganese sulfate pentahydrate, zinc as zinc sulfate heptahydrate, potassium as potassium iodide or potassium chloride, sodium as sodium citrate dihydrate, calcium as calcium glycerophosphate, magnesium as magnesium sulfate heptahydrate, and others. About 3,000 to 5,000 mg of minerals are employed per 80 g of the nutritional composition, and, as such, the concentration of minerals is about 2 to 8% by weight. 
     Particularly useful are compositions containing iron and calcium in amounts greater than those presently employed in known elemental nutritional diets, in view of the growth requirements of children. For example, about 30 to 60 mg of gluconic acid iron salt dihydrate or 1,400 to 2,000 mg of calcium glycerophosphate may be employed per 80 g of the nutritional composition. 
     When the nutritional composition of the present invention is manufactured as a finished good, preservatives, such as potassium sorbate, and emulsifiers, such as polysorbate and soy phosphatides, can be added, thereby reducing the ability of the composition to support growth of contaminating microogransims while in powder form or in solution and making the dissolution or emulsification of the composition easier. 
     When the nutritional composition produced in accordance with the present invention is administered to a small child, emulsified and homogenized material is preferred for ease of administration and digestion. 
     The nutritional composition of the present invention is widely useful, since it can be administered either by intestional intubation or oral ingestion. A non-toxic carrier suitable for human use, such as water, milk, or an aqueous solution or suspension of various non-toxic organic or inorganic substances, may be used as an aid in the administration of the composition. 
     When the composition is administered orally, it is employed in the form of a paste or solution and is administered together with milk. Further, the nutritional composition may contain flavors, seasonings, acidophilus-containing-drinks, or other materials to increase pleasure of eating and drinking. 
     When the nutritional composition is administered by intestional intubation, it may be used as a water solution or mixture, e.g., with warm water, in the concentration of, for example, about 5 to 40% (w/v). 
     Products according to the present invention can be used widely for the nutrition of sick children. Examples include controlled nutrition before or after a surgical operation and improvement of nutrition in cases of poor digestion or malabsorption. 
    
    
     Having generally described the invention, a more complete understanding can be obtained by reference to certain specific examples, which are provided herein for purposes of illustration only and are not intended to be limiting unless otherwise specified. 
     EXAMPLES 
     The following substances were homogeneously mixed in the powder state: 
     
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Substance                 Weight                                          
______________________________________                                    
L-histidine monohydrochloride monohydrate                                 
                          0.380   g                                       
L-isoleucine              0.519   g                                       
L-leucine                 1.004   g                                       
L-lysine monohydrochloride                                                
                          0.949   g                                       
L-methionine              0.159   g                                       
L-cysteine hydrochloride monohydrate                                      
                          0.313   g                                       
L-phenylalanine           0.310   g                                       
N--acetyl-L-tyrosine      0.538   g                                       
L-threonine               0.496   g                                       
L-tryptophan              0.186   g                                       
L-valine                  0.537   g                                       
L-alanine                 0.960   g                                       
L-arginine                0.693   g                                       
Mixture of di-L-aspartic acid monomagnesium                               
and L-aspartic acid monopotassium in the                                  
ratio 1:1                 0.547   g                                       
glycine                   0.227   g                                       
L-glutamic acid           0.747   g                                       
L-proline                 0.976   g                                       
L-serine                  0.883   g                                       
dextrin                   62.88   g                                       
soybean oil               2.400   g                                       
retinol acetate           0.372   mg                                      
thiamine hydrochloride    0.323   mg                                      
riboflavine sodium phosphate                                              
                          0.427   mg                                      
pyridoxine hydrochloride  0.445   mg                                      
cyanocobalamin            1.200   μg                                   
ascorbic acid             28.600  mg                                      
ergocalciferol            8.532   μg                                   
tocopherol acetate        5.507   mg                                      
phytonadione              14.667  mg                                      
calcium pantothenic acid  1.987   mg                                      
nicotinamide              3.667   mg                                      
biotin                    65.333  μg                                   
folic acid                73.333  μg                                   
choline bitartarate       29.880  mg                                      
gluconic acid iron salt dihydrate                                         
                          43.97   mg                                      
cupric sulfate pentahydrate                                               
                          1.373   mg                                      
manganese sulfate pentahydrate                                            
                          2.173   mg                                      
zinc sulfate heptahydrate 214.7   mg                                      
potassium sorbate         120.    mg                                      
&#34;polysorbate 80&#34;          117.6   mg                                      
soy phosphatide           16.8    mg                                      
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     The above mixture was converted to a paste with water or dissolved in water for oral administration. Eighty grams of the above mixture was dissolved in warm water to give 300 ml of solution (26.7% (w/v); specific gravity, 1.09) to form the standard solution used for administration by intestinal intubation. Further mixtures or solutions having several concentrations in the range from 5 to 40% (w/v) were produced for administration through a fine catheter into the duodenum or jejunum of a child. 
     Having now fully described the invention, it will be apparent to one of ordinary skill in the art that many changes and modifications can be made thereto without departing from the spirit or scope of the invention as set forth herein.