WO2008104867A1 - High calorie and easily digestible food - Google Patents

Abstract

This invention relates to the medicinal field. Specifically, the invention refers to a solid or semi-solid, high calorie food for patients suffering from malnutrition and various degrees of pancreatic insufficiency, because it contains a large amount of fats from various origins and digestive enzymes from various origins that exhibit lipolytic, proteolytic or amylolytic activity.

Description

"HIGH CALORIE AND EASILY DIGESTIBLE FOOD"

STATE OF THE ART OF THE INVENTION

Scope of the Invention

This invention is related to the medical field. Li particular, the invention involves a solid or semi-solid food with a high caloric content, which would preferably be administered to patients suffering from malnutrition and various degrees of pancreatic disorders as this is a food type containing large amounts of fats from various origins and digestive enzymes from various sources that exhibit lipolytic, proteolytic and amylolytic activity.

Description of Prior Art

Before starting to describe this invention, it is best to explain the current situation concerning this problem as regards the absorption of foods ingested by a large percentage of the world's population. Typically malabsorption may result from the failure to absorb sugars, fats, proteins or specific vitamins, or it maybe a general lack of nutritional absorption.

Malabsorption may be accompanied by diarrhea, swelling or colic, growth retardation, frequent and sizeable bowel movements, muscular weakness and abdominal distention. The decrease in caloric uptake, even when eating properly, is, in many cases, due to a problem with absorbing the ingested food. Malabsorption syndrome (MAS) is characterized by an inadequate absorption of fats, liposoluble and other vitamins, proteins, carbohydrates, electrolytes, minerals and water.

Under normal circumstances, foods comprised of fats, proteins, carbohydrates, vitamins and other components, must be reduced by digestive enzymes, in particular the first three elements listed above, since they are complex compounds until broken down into simple units that allow for their absorption.

Basically, malabsorption results from a modification of at least one of the following digestive functions: 1. Intraluminal digestion, in which proteins, carbohydrates and fats are broken down into assimilable forms. The digestive process begins in the mouth with saliva, continues in the stomach with the peptic digestion of proteins and ends in the small intestine with the emulsive action of biliary salts and of pancreatic enzymes.

2. Terminal digestion, which affects the hydrolysis of the carbohydrates by disaccharidases and peptidases in the brush border of the apical end of the intestinal epithelial cells.

3. Transepithelial transport, where nutrients, liquids and electrolytes are transported across the epithelium of the small intestine to be distributed by intestinal vascularization, hi particular, the fatty acids thus absorbed are then combined as triglycerides and, together with cholesterol, join with chylomicrons and are distributed by the intestinal lymphatic system.

Many are the illnesses and pathological processes that produce MAS. hi many of the poor absorption processes, the dysfunction of some of the physiopathological mechanisms is predominant, but other mechanisms may also contribute to the problem. These may be classified as: a) Hydrolysis defects or intraluminal solubilization- examples include: Primary pancreatic insufficiency;

Secondary pancreatic insufficiency;

Lack of intraluminal biliary salts;

Excessive bacterial growth such as: blind loops, multiple stenosis, jejunal diverticula and fistula. Post gastrectomies;

Scleroderma; and

Neuromuscular dysfunction. b) Primary alterations of mucous cells, examples of which are: Disaccharidase intolerance and monosaccharide malabsorption; Abetalipoproteinemia;

Malabsorption of vitamin B 12;

Loss of parietal cells (pernicious anemia); Ileal dysfunction or resection; and Cystinuria and Hartnup's disease. c) Reduced surface of the small intestine, examples of which include: Gluten-sensitive enteropathy (celiac disease);

Refractory disease; Whipple's disease; Short bowel syndrome; Crohn's disease; Eosinophilic and allergic gastroenteritis; and

Diffuse enteritis associated with lymphoma. d) Infections, examples of which include: Acute infectious enteritis;

Parasitic infections; and Tropical diseases. e) Lymphatic obstructions, examples of which include: Lymphoma;

Tuberculosis and tuberculous lymphadenitis; and

Lymphangiectasia. f) Iatrogenic diseases, for example:

Total or subtotal gastrectomy;

Distal or by-pass ileal resection; and

Post-radiation enteritis. g) Induced by drugs, for example: Cholestyramine;

Colchicine;

Irritating laxatives;

Neomycin; para-aminosalicylic acid, and phenindione h) Unknown mechanisms, such as, for example:

Hypogammaglobulinemia; Carcinoid syndrome; Diabetes mellitus; Mastocytosis; Hyperthyroidism; Hyperthyroidism; [sic]

Hypocorticism; and Hypoparathyroidism.

Clinically, the similarities among MASs appear to be more than the differences. Malabsorption may affect growth and development or it may lead to specific illnesses the consequences of which affect many organic systems and produce several pathologies, some of which we will attempt to discuss below. With regard to the digestive tract the following is seen:

Diarrhea (due both to poor absorption of nutrients and to excessive intestinal discharge); Flatulence;

Abdominal pain; Loss of weight; and Mucositis due to a lack of vitamins.

Within the hematopoietic system the following can be observed: Anemia from iron deficiency;

Pyridoxine;

Foliates or vitamin B 12; and hemorrhaging from vitamin K deficiency.

Within the muscular-skeletal system the following is usually observed: Osteopenia and tetany from the malabsorption of calcium, magnesium, vitamin D and proteins.

Within the endocrine system the following may be observed: Amenorrhea; Impotence; sterility due to generalized malnutrition; and

Hyperparathyroidism due to chronic calcium and vitamin D deficiency. The following may be observed on the skin:

Purpura and petechia due to vitamin K deficiency; Edema from protein deficiency;

Dermatitis and hyperkeratosis from a lack of vitamin A, zinc, essential fatty acids and niacin.

Within the nervous system: peripheral neuropathy due to vitamin A and B 12 deficiency.

The classic symptoms of malabsorption (steatorrhea) are: the production of bulky, frothy, oily, yellowish to grayish feces, together with loss of weight, anorexia, abdominal bloating, and borborygmus and muscular atrophy. The most frequent MASs are celiac disease, chronic pancreatitis and frequent intestinal parasitosis in children, caused by the protozoan Giardia lamblia (Giardiasis). Acute pancreatitis is an inflammation (irritation and bloating) of the pancreas, an elongated gland located behind the stomach that secretes digestive enzymes and insulin and glucagon hormones. The principal causes of acute pancreatitis in adults are calculi, other illnesses of the gallbladder (gallstones) and alcohol consumption. Other causes include:

Viral infections (mumps, Coxsackie B virus, pneumonia from Mycoplasma and Campylobacter); Traumatic injury

Pancreatic surgical procedures; Surgical procedures in the common bile duct Certain medicines (especially estrogen, corticosteroids, thiazide diuretics and azathioprine); Acute pancreatitis may also be caused by an abnormal pancreas structure, genetic factors (hereditary pancreatitis), high lipid levels in the blood (hypertriglyceridemia) and cystic fibrosis complications. The cause of pancreatitis is not well known. It is believed that the enzymes that are secreted normally by the pancreas in an inactive way are activated within the pancreas and begin to absorb the pancreatic tissue. This process is called autodigestion and causes inflammation, hemorrhaging and damage to the blood vessels. This illness affects men more frequently than women and excessive alcohol consumption is an important risk factor.

Chronic pancreatitis is often related to a progressive destruction of the pancreas from repeated outbreaks of acute pancreatitis, with minor symptoms. It develops in the same type of patients who are likely to suffer from acute pancreatitis, especially male alcoholics who are middle aged and, less frequently, in patients with bile duct disorders. Hypercalcimia and hyperlipidemia also predispose people to chronic pancreatitis. There exist relatively infrequently special forms of chronic pancreatitis such as tropical non-alcoholic pancreatitis and hereditary pancreatitis whose cause is not well known. About 12% of patients with chronic pancreatitis present with a divided pancreas [Pancreas Divisum] together with an anomalous duct system and stenosis of the duodenal papilla. Nevertheless in up to 40% of patients with chronic pancreatitis no predisposing factor has been identified.

The pathology of chronic pancreatitis is varied. It has been proposed that it can be triggered by certain factors such as:

1. Obstruction of the ducts by concretions, due to changes caused by alcohol both in duct and acinar secretions as well as in the biosynthesis of lithostatins (protein from the pancreatic calculi). Under normal circumstances, this protein inhibits the intraluminal precipitation of calcium carbonate. Its deficiency would favor calcium precipitation, even though the increase in intraluminal calcium may exceed the inhibiting capacity of lithostathine, with a tendency to form caculi that obstruct light.

2. Fat necrosis and interstitial bleeding, which start a succession of processes: perilobular fibrosis, duct deformation and changes in the pancreatic secretion of the duct flow, which through a process of retroalimentation causes inflammation, necrosis and new fibrosis, and can even destroy much of the parenchyma.

Chronic pancreatitis causes inflammation and scarring of the pancreas' tissue, which causes the inability of this organ to produce the correct amount of chemicals (enzymes) that are necessary for the digestion of fats. It furthermore interferes with insulin production, which can result in diabetes. People with chronic pancreatitis have abdominal pain attacks and digestive disorders. The symptoms may become more frequent as the condition worsens and they may simulate pancreatic cancer.

Clinically, chronic pancreatitis may appear in the form of repeated attacks of pain in the abdomen that are of between a slight and a moderate intensity, mainly in the upper abdomen. The pain may last from hours to days until ultimately becoming continuous. Cases have also been documented in which the pain has worsened upon eating or drinking and in some cases the pain has also been observed to irradiate towards the back. Nevertheless, in many cases, the illness is asymptomatic until the patient finally develops pancreatic failure, in the endocrine sector as well as in the exocrine sector. Chronic pancreatic failure in the exocrine sector leads to the failure to produce pancreatic secretion that is rich in digestive enzymes such as lipase, amylase and trypsin, a protease. Thus, the decrease in lipase produces a decrease in the lipolytic capacity of the digestive tract, which causes the inability to break down triglycerides into its component parts, glycerol and fatty acids, thereby making them unable to be absorbed by the intestinal epithelium. The presence of undigested triglycerides in the digestive tract causes feces with an elevated fat content (steatorrhea) with a distended abdomen, flatulence, changes in the intestinal microbial flora and changes in bowel movements, with bulky and doughy feces, always having a bad odor. At the same time, the non digestion of fats impedes or makes difficult the absorption of liposoluble vitamins, such as A, D, E and K, for which cause, in the course of time, the patient may present with hypovitaminosis. Changes in bowel movements and the lack of fat absorption quickly lead to a set of malnutrition symptoms mainly characterized by a decrease in the amount of energy assimilated, although may also subsequently decrease the amount of plastic foods such as proteins and sources of calcium that are assimilated (), thereby making the malnutrition complete.

The decrease in amylase is evidenced by an inability to digest starches and complex polysaccharides that allow for the absorption of their monomelic components. Thus, complex sugars pass into the colon where they are broken down by intestinal bacteria, producing a large quantity of lactic acid, hydrogen and methane, causing abdominal bloating, flatulence, widespread abdominal pains and borborygmus. The decrease in sugar absorption also leads to an energy deficiency that is added to the deficiency produced by the lack of absorption of fats.

The decrease in the trypsin, pancreatic protease, leads to failure to digest proteins into their constitutive elements, amino acids, judging by the fact that they may not be properly absorbed. As time goes on, signs of protein malnutrition and essential amino acid deficiency begin to become evident. All of this contributes to the set of symptoms of malnutrition exhibited by individuals who develop clinically manifest pancreatic insufficiency. The increase in intestinal passage and all changes in intestinal functions also cause a deficiency in the absorption of other nutrients such as hydrosoluble vitamins and trace elements and essential minerals such as iron, copper, zinc, magnesium manganese, selenium, etc.

The treatment for this type of pathology for the most part attempts to reduce the pancreas' stimulation, prevent indigestion, reduce pain and treat diabetes (if present). The same treatment may consist of consuming a low fat diet, obtaining adequate liposoluble vitamins and calcium in the diet, taking analgesics or surgically blocking nerves to alleviate pain, administering insulin to control blood sugar levels, and administering pancreatic enzyme supplements to correct inadequate production. Patients should not drink alcohol. In the event of finding an obstruction, surgical treatment is recommended and, in advanced cases, all or part of the pancreas may be surgically removed.

Even though in absolute terms pancreatic failure associated with a paradigmatic genetic illness, cystic fibrosis, is infrequent, its high incidence among those who have the illness and its interference with those patients¹ quality of life from an early age, makes this pancreatic failure the preferred target for the exogenous administration of replacement enzymes.

Cystic fibrosis (CF) is the most common cause of chronic pulmonary disease in children and youths and the most common mortal genetic/hereditary disorder affecting Caucasians in the United States, affecting one in 5,000 live births, and characterized by much thicker than usual corporal secretions. Thus, these patients develop plugs of secretions in the bronchi, that make them susceptible to infections and irreversible pulmonary damage and plucks of thick secretion in the pancreatic duct which quickly leads to a failure in the producer organ of the principal digestive enzymes (lipase, amylase and protease), thereby causing poor digestion of foods, especially fats, and given the fact that they are not properly absorbed, leading to a state of chronic malnutrition. Pathogenetically, the disease is characterized by a primary defect in the regulation of chloride transport in the epithelial cells. In normal epithelia, chloride is transported by special channels in the plasma membrane, the chloride channels, whose opening is governed by an increase in the cyclic AMP followed by the activation of a protein kinase A that phosphorizes the channel. The lack of chloride transport in the sudoriferous gland ducts leads to a decrease in the reabsorption of sodium chloride from light, thereby increasing the secretion of this salt in the sweat, hi the epithelium of the respiratory paths, chloride deficiency in the chlorine channels gives rise to a loss or reduction in chloride secretion in the airways. Active sodium absorption also becomes increased in cystic fibrosis. These two ionic changes increase the reabsorption of acute [sic] from light, thereby decreasing the hydric content of mucus that coats the cells of the respiratory mucosa. Dehydration of the layer of mucus leads to a defective mucociliary activity and an accumulation of viscose and hyperconcentrated secretions that obstruct the airways and predispose patients to recurring pulmonary infections. Other organs, such as pancreatic ducts and biliary ducts, or male sexual ducts suffer the same consequences.

The genetic anomaly in CF is found in the gene codifying the protein that acts as the chlorine channel, located in chromosome 7, in band q31-32. The protein, known as CFTR (cystic fibrosis transmembrane conductance regulator) contains various functional regions and a regulatory region that contain phosphorylation points for protein kinases A and C. Some two hundred mutations of the CF gene have been identified. Seventy percent of those cases contain a deletion of three nucleotides that codify Phenylalanine at the 508 position of the amino acid chain, leading to the protein's degradation before it is secreted by the Golgi apparatus. Other mutations affect other CFTR regions leading to somewhat important dysfunctions. The gravity of the resulting disease is generally correlated with the degree to which the transport of secondary chloride to the mutation is affected: at one end of the spectrum is the F508 homozygote, which is associated with an almost complete absence of the membrane's CFTR, pancreatic failure and pulmonary affectation of variable intensity. In the middle are certain F508 heterozygotes that may have a proper pancreatic function in the long term but are not protected against pulmonary injuries. At the other end are mutations of the transmembrane regions, wherein the chlorine transport is relatively normal and the clinical signs are minimal. The life expectancy of these patients was no more than 26 years, but with the establishment of new effective therapies, the life expectancy has increased to almost normal ages. Pulmonary infection is combated with a nebulizable antibiotic drug and digestive problems are solved using capsules with enzymes originating from pigs.

In Argentina statistics show that there are some 1,500 registered cases and others that have not been recorded (because they have not been diagnosed even though perinatal diagnosis is mandated by Law).

The majority of CF deaths are caused by pulmonary infections due to the fact that natural barriers against infections, such as bronchial secretion and sweeping movement of mucus towards the exterior, are no longer present in patients with CF. The accumulation of mucus in the bronchial lumina, apart from obstructing the normal flow of air, act as a breeding ground for the proliferation of bacteria, including Pseudomona aeruginosa, which is extremely difficult to eradicate in these patients. Practically all patients with moderate to severe CF (the majority of clinical forms) have Pseudomona infections.

On the other hand, given the fact that patients with CF do not have pancreatic sufficiency, they are unable to completely digest food; hence, they become malnourished and present with what is called malabsorption syndrome, characterized by the inability to digest fats in food because of a lack of the lipase enzyme, and therefore eliminate them in fecal material. Together with their inability to absorb fat, they are also unable to absorb the liposoluble vitamins A, D, E, and K.

Between 85 to 90% of the patients suffering from pancreatic insufficiency, the prescription of pancreatic extracts (PEs), generally porcine, is justified. These extracts provide enzymes the purpose of which is to facilitate digestion of the following food groups: fats, proteins and sugars. This involves lipase, trypsin and amylase. Thanks to these extracts, the feeding may be hypercaloric and rich in lipids.

PEs are provided in the form of "gastro-protected" capsules, i^, they resist the stomach's acidity. They may be micro-tablets (micro-capsules of the same size) or microspheres (micro capsules of unequal size). PEs should be taken before meals. For very small children, the capsules may be opened and mixed in a drink or acidic food as they are not pleasant tasting (e.g. apple juice). They should never be chewed.

The FDA has recently given the green light to change the origin of the enzymes administered to patients with CF. Within a relatively short period of time - no more than 2 years - all the enzymes for CF will have to be of a microbial or other origin, and the use of porcine enzymes will be prohibited.

For this reason, a product that combines lipase with biliary salts is being tested, with very good results now in phase II stages. Fats and glucides provide energy to our organism, since every gram of fat produces more than double the amount of energy as other nutrients, and they are also essential for the absorption of vitamins (liposoluble vitamins), for synthesizing hormones, for filling organs, for cellular membranes and for sheaths that cover nerves. In the foods we eat daily we find saturated and unsaturated fats. The saturated fats are more difficult for an organism to use as it is with difficulty they combine with other molecules, and, in certain conditions, are the fats that accumulate in the interior of arteries forming plaque (atherosclerosis). Cholesterol and phospholipids also rate among the nutritionally important as they form the walls of our cellular membranes.

It is recommended that fats comprise between 20 and 30% of the energy in our diet, and it should be made up of 10% saturated fats (animal fats), 5% unsaturated fats (olive oil) and 5% polyunsaturated fats (fats from dried fruit and seeds). In cystic fibrosis fat is an indispensable part of the daily diet. It is important to point out the excessive consumption of animal fats in any person increases the risk of diseases such as myocardial infarction, embolisms or arteriosclerosis. Acute or chronic malnutrition is a frequent sign in patients with CF; nevertheless there is no reason to accept deficient growth, unless in terminal cases when the possibility of a transplant is not being considered. The same malnutrition relates to multiple causes. Different mechanisms related to the physiopathology of the disease cause an increase in the energy requirements and deficiencies in vitamins and micronutrients. hi a comparative study between two important CF centers, one in Toronto, Canada and the other in Boston, United States, a significant difference was demonstrated in the mean survival. While the patients in Toronto were given diets rich in fats and high doses of pancreatic enzymes, as this was the therapeutic strategy used since the 1970's, those in Boston received diets with a low fat content and low doses of enzymes. There were no significant differences in the treatment of the disease with respiratory apparatuses, and the best survival was ascribed to the nutritional state. This study also demonstrated that restrictions in the percentage of ingested fats were not necessary and marked the beginning of different nutritional interventions, designed to increase caloric consumption, hi this way, by implementing new ways of implementing nutritional management, approximately 20% of the prevalence of malnutrition was reduced in patients with CF in the United States between the years 1986 and 1996 was reduced. hi another study carried out by Corey and Farewell, patients from the

Canadian CF registry were analyzed, and malnutrition was found to be an independent factor for predicting mortality, a fact that was corroborated by other authors.

Depending on the state of the pulmonary disease, physical activity and the degree of malabsorption, exceeding the nutritional recommendations for healthy individuals of the same age by approximately 50%, with about 35% - 40% of fat content in the diet is clearly recommended. hi this regard, several products are offered on the market as calorie supplements. In general, they are not accepted because of their taste and, in the case of children, because of the need to not feel different from their peers.

Given the state of the art regarding caloric and enzymatic supplements available on the market that are intended for these deficiencies, it would he helpful to have a supplement that would allow for a better quality of life in those patients who suffer from pancreatitis and malnutrition.

BRIEF DESCRIPTION OF THE INVENTION A high calorie, easily digestible food, intended for persons with nutritional deficiencies and digestive problems.

The product in its various applications provides a solid or semisolid high calorie food supplemented with selected digestive enzymes from the enzyme group with lipolytic, proteolytic and amylolytic activity and a high fat content. High calorie food is composed of fats, carbohydrates and proteins, of different origins and can be easily digested.

High calorie food may be considered to provide a fat substance selected from the cocoa butter and peanut butter group.

High calorie food includes enzymes which may be of animal, microbial or biotechnological origin in which the said enzymes are protected by an enteric coating consisting of a complex polymer, where the polymer is preferably Eudragit. High calorie food may be supplemented with other nutrients from the groups of vitamins, fibers, oligoelements, substances with therapeutic activity, and substances with pharmacological activity. It also provides a preparation method for the final mix of high calorie food and a method of preparation of high calorie food in the form of a solid little bar.

DETAILED DESCRIPTION OF THE INVENTION Referring now specifically to the invention, it is comprised of a solid or semisolid food with a high caloric content supplemented by digestive enzymes selected from the group of enzymes with lipolytic, proteolytic and amylolytic properties and a high fat content. The invention also provides a method of preparation of the final mix of the high calorie food.

More particularly, the invention refers to a solid or semi-solid sustenance with a high caloric content which is characterized by having a nutritional composition with a large amount of fats from different sources. During its preparation a number of digestive enzymes from any origin that increase the absorption of nutrients and show a lipolytic, proteolytic and/or amylolytic activity, is added, being careful not to apply enough heat during its preparation to denaturalize the digestive enzymes. In another of its forms, the food consists of digestive enzymes in a fat paste or in a fat based material mixed with flavorings, agglutinating agents and complex sugars. These components may be from varied origins, including animal, vegetable and synthetic. The flavorings, agglutinating agents and sugars and other components may be mixed in a wide variety of proportions, depending on the individual objectives and the given patient population. A person of ordinary skill in the art will appreciate the fact that the selection and amount of the components listed may vary without compromising the desired objective or the utility of the food. In one of its forms the fat substance comprises between 10% and 70% of the wet weight of the high calorie food. hi one of its forms, the food contains a cocoa and/or peanut butter paste combined in adequate proportions with the other ingredients so that it can be delivered in the form of a bar, containing a sufficient quantity of enzymes. The said enzymes, whether a single enzyme or various combinations of enzymes, shall have a value of between 400 and 2,000 international units expressed as the lipolytic function per gram of fat incorporated in every food ration and more preferably, that value will be 1000 units per gram of fat. The food may be made more palatable and pleasant to the taste when coatings are added with different flavors, textures and colors, without modifying in any way the energy function that the food should provide and the amount of enzymes sufficient to supplement the deficit with which the individual for whom it is intended presents. The indications of the food are for any patient suffering from malnutrition and various degrees of pancreatic insufficiency.

The fats of which the food may be composed may be selected from the following list, the list not excluding other fats that a person of ordinary skill in the art may select and add to the product without difficulties: Lard; Fats of animal origin;

Margarine; Hydrogenated fats of a synthetic origin; Cocoa butter; Peanut butter; Fats of vegetable origin; Saturated fatty acids; Unsaturated fatty acids;

By-products of the same; and Mixtures of the same.

The proteins included in the food may be selected from the following list, without limiting the use of other ingredients not included on the list, and which a person of ordinary skill in the art may select and add to the product without difficulties:

Whey;

Powdered whole milk; Powdered nonfat milk; Vegetable proteins;

Soy proteins; Ovalbumin; Lactalbumin; Albumin; Gluten;

Proteins and synthetic polypeptides; By-products derived from those above; and Mixtures of the same.

The same proteins are preferably present between 10% and 70% of the wet weight of the high calorie food.

Sugars included in the food may be selected from the following list, without this limiting the use of other ingredients not included here, and a person of ordinary skill in the art being able to select and add to the product without difficulties:

Sucrose; Mactose;

Maltose; Maltodextrins; Fructose;

Complex polysaccharides;

Starch;

Glycogen; Vegetable syrups;

Corn syrup;

Insulin;

Pectin;

Dextrose; Alginic acid;

Agar;

Cellulose;

Carboxymethyl cellulose;

Fructooligosaccharides; Honey;

By-products derived from the above; and mixtures of the same. Preferably, these carbohydrates make up between 10% and 70% of the wet weight of the high calorie food.

The food may include other ingredients including the following, without this list limiting the use of other ingredients that a person of ordinary skill in the art may select and add to the product without causing problems: natural and synthetic agglutinating agents;

Trace elements;

Zinc, copper, iron, magnesium, manganese, selenium and their salts; Hydrosoluble vitamins;

Vitamin C, Vitamin B-complex, folic acid and their salts;

Liposoluble vitamins;

Vitamins A, D, E and K;

Natural fiber; Fibers of animal origin;

Fibers of vegetable origin;

Various flavorings; Various preservatives; Whole or fragments of fruits; Dry or desiccated fruits; Grains and cereals; Processed grains and cereals ("puffed");

Small seeds and preserves; and Various coatings.

The enzymes that may be incorporated into the product may be selected from the following list, without this list limiting the use of other enzymes that a person of ordinary skill in the art may select and add to the product without causing problems: Porcine pancreatine; Desiccated porcine pancreas; Bovine pancreatine; Porcine pancrelipase; Bovine pancrelipase;

Desiccated bovine pancreas; Lipase from animal origin; Trypsin of animal origin; Amylase of animal origin; Lipase of microbial origin;

Trypsin of microbial origin; Amylase of microbial origin; Lactase or beta-galactosidase of microbial origin; Lactase or beta-galactosidase synthesized by genetic engineering; Lipase synthesized by genetic engineering;

Amylase synthesized by genetic engineering;

Trypsin synthesized by genetic engineering; Proteases of animal origin; Proteases of microbial origin; Proteases synthesized by genetic engineering;

Phospholipases of animal origin; Phospho lipases of microbial origin; Phospholipases synthesized by genetic engineering; Animal nucleases; Microbial nucleases;

Nucleases synthesized by genetic engineering. In one of the product's forms, the enzymes are protected by an enteric coating that protects them from being degraded by gastric juices. The enteric coating may be a complex polymer and preferably, the polymer complex is Eudragit®. The enteric coating of the enzymes is developed using available conventional techniques. The manner of presentation of the enzymes with the enteric coating may be in the form of sugar-coated pills, mini-sugar coated pills, microencapsulates, microspheres, mini-microspheres, pellets, minipellets, minitablets. Micro tablets and any other form that may be obvious to the eyes of a skilled person.

The food may be packaged in commercially available containers that are made of different materials such as cardboard, plastic, aluminum, polyethylene, silica paper, paper, wax paper, glass, tinplate, and others.

The product may contain functional nutrients that the body may eventually lack either permanently or temporarily, a deficiency that is easily detectable by a person of ordinary skill in the art. These nutrients may be of a pharmacological nature, or they may be elements with pharmacological activity of a different nature, that may provide a benefit to patients who also suffer from other pathologies or health related conditions. Among these the following may be cited without limiting the scope of this invention:

Taurine and its salts Taurocholic acid;

Deoxycholic acid; Chenodeoxycholic acid; Biliary salts; Biliary acids; Essential amino acids and their salts;

Amino acids and their salts Lipoic acid and derivatives; Choline and its derivatives; Omega 3 fatty acids; Omega 6 fatty acids;

Omega 9 fatty acids; Cisternae

Acetylcysteine; Prebiotics; Prebiotics [sic]; and

Orally administered pharmacopoeic medicines. These may be mixed with the product which is the subject of the invention in proportions that are adequate to obtain a therapeutic or prophylactic effect.

The product created in this manner is designed for patients suffering from diverse conditions or pathologies in which it is necessary to reinforce or increase the caloric intake and in which there is a deficit or lack of digestive enzymes. Among these conditions or pathologies are malnutrition associated with pancreatic insufficiency and cystic fibrosis.

Given this nutritional problem in these types of patients, a food was designed that brings a high number of calories, and which in turn that contains sufficient amounts of replacement enzymes so that the consumer may not need to consume a determinate number of pancreatine capsules to compensate for the increase in calories provided. This food (functional) may replace the functional foods that exist on the market today because it contains a number of digestive enzymes that are capable of producing therapeutic or prophylactic effects, it is highly palatable, and is widely accepted by patients. The food was designed to be eaten between meals, and outside of the patient's house (for example, during school recess).

The food designed in this manner looks like a bar that is similar to a candy bar. This form of presentation does not rule out other forms such as, for example, powder, paste, cream, ice cream, etc., and this list does not limit the forms of presentation to the above mentioned presentations, since the food may be presented in other ways.

Among the advantages of presenting the sustenance in the form of a solid little bar are the following: 1) It is not necessary for the patient to bring enzymes in order to be able to ingest a high calorie food such as the bar in this invention.

2) It is not necessary to eat the entire bar, as it may be divided because the enzymes are distributed evenly and proportionally to the amount of fat. 3) It is a functional food, which means it is easy to register in a regulatory sense.

4) It is extremely practical, compared to other energy products that exist on the market, which are presented as a powder to be prepared in shakes or added to food. 5) It is easy to decide on the dosage, as 1 , 2 or more bars or portions thereof may be prescribed depending on the case.

6) The patient does not suffer social inconveniences by having to stop their routines to prepare a shake or publicly take the enzymes he or she needs.

7) The number of Kcal per bar is greater than the calories provided by commercial other products used as hypercaloric supplements.

8) It is innocuous for people who do not suffer from malnutrition or pancreatic insufficiency.

9) The option of adding other enzymes to the product prevents the inconvenience of having to ingest medications together with hypercaloric supplements.

This invention is best illustrated by the following examples, which are only illustrative and should not be interpreted as a limitation imposed on the scope of the [sic] exclusive right invoked herein.

EXAMPLES

Example 1 : Composition of the semisolid bar

Given the conditions that this functional food must meet, a hypercaloric bar resembling a sweet with approximately 64 grams of fat and approximately 380 Kcal, was designed; it is easy to transport, pleasant tasting (easily interchangeable with fruit, chocolate, vanilla, coffee, "Mantecol" peanuts, and other flavors), and contains a given number of pancreatic enzymes mixed in the material. Example 2: Production of a nutritious, high calorie

To produce a high calorie nourishing bar the following steps were taken:

Heating a mixture of high fructose syrup and fats in a double boiler to a temperature of 40° C until the fat is mixed in; Adding semisolid peanut butter to the liquefied fat;

Mixing well with a low-speed mixer;

Separately dispersing the pancreatic enzymes in normal table sugar and powdered milk;

Slowly adding the prepared powder to the mixture; Mixing in a low-speed mixer for 15 minutes, until reaching a soft and homogenous paste;

Pouring into a metallic mold in order for the bar to conform to its corresponding weight and measurement;

Cooling Cutting up the remaining ingredients; and

Placing in a chocolate enrober for covering, deposit the bar on a metal rack and allowing the liquefied chocolate to run over the bar until it is completely covered.

Alternatively, a double boiler may be used by completely immersing the bar in liquefied chocolate.

Once out of the enrober, the bar is allowed to cool to a temperature of 18- 20°C for 30 minutes.

Finally, it is packaged.

Example 3: Stability of the lipase contained in the nutrition bar

In order to determine whether the enzymes added to the nutrition bar, created using the techniques described in example 2, maintained their biologic activity over the long term, the following experiment was designed: a) Separation of the enzyme granules: A bar prepared 6 months previously, using the technique described in example 2, which was maintained during that time at room temperature and packaged in an aluminum and plastic heat-sealed vacuum-packed wrapper, was heated on a metal microscope slide to 40° C until softened. Using a spatula, the melted bar was spread out on the same microscope slide and the granules containing the pancreatic enzymes were separated by a machine with bearings. Once separated, they were washed with chlorohexane to remove the fat particles that may have remained attached to their surface. The chlorohexane was allowed to evaporate at room temperature. b) Dissolution of the enteric coating:

The enteric-coated enzyme granules thus obtained were placed, after being weighed, in a salt phosphate buffer with a pH of 7.4 for 3 hours in a double boiler at 37° C, using intermittent agitation, in order to dissolve the enteric coating. c) Determining the lipolytic activity:

The lipolytic activity was measured using a commercial lipase kit (Biosystems S.A., Barcelona, Spain) with the following basic practice:

The lipase catalyzes the hydrolysis of the chromatic substrate 1,2-0- dilauryl-rac-glycero-3-glutaric acid- (6-methylresorufm) -ester yielding 1,2-0- dilauryl-rac-glycerol and the glutaric acid- (6-methylresofurin) -ester, an unstable intermediate product. In an alkaline solution, this spontaneously breaks down into a glutaric acid and methylresofurin. The catalytic concentration is determined starting with the speed at which the red color forms when measured to 570 nm in an automatic analyzer or in a spectrophotometer with a cuvette that is thermostatizable to 37° C for readings to 570 +/- 20 nm.

To make determinations, the enzyme sample obtained was diluted with distilled water (1:10,000) and the ingredients mixed in an 800 uL cuvette of the Reactive A that was provided in the commercial kit along with 12 uL of the diluted sample; the ingredients being preheated to 37° C.

The cuvette was placed in the spectrophotometer and at 5 minutes exactly, 400 uL of the Reactive B from the commercial kit, also preheated to 37° C, was added to it and well mixed.

After 3 minutes, the initial absorbance was noted and then new readings were taken every minute for another three minutes. The increase in absorbance was calculated per average minute (Δ [delta] A/min). At the same time, the same procedure was carried out; however a calibration solution included in the commercial kit, was used in lieu of our enzymatic sample, in order to calculate the concentration of lipase in the sample, in accordance with the following formula: delta Δ /min. sample

X C calibration = U/L

Δ A/min. calibration

As a stability control, the same determinations were carried out on a similar volume of pancreatic enzyme granules belonging to the same portion used for the preparation of the nutrition bars, which were also maintained at room temperature during the same time as the bars.

Results: The lipase activity of the granules contained in the nutrition bar was 48.634 U/L, while the lipase activity of the granules maintained at room temperatures and used as the control were 50.660 U/L. Conclusions: there was a difference of 4% between the lipase activity of the control sample and the lipase activity of the sample contained in the nutrition bar and maintained in the bar for 6 months. This difference may be due to the different sizes of the granules making up each of the samples, and taking into consideration the fact that each granule contains a central enzyme nucleus and a peripheral covering consisting of an enteric coating; it is possible that this difference is due to a different enzymatic concentration between each granule. In any case the difference of 4% is considered to be insignificant, for which reason it is deduced that the lipase contained in the bar does not lose its activity for at least 6 months, or stated in another way, it is stable for 6 months.

REFERENCES

Carey M, Farewell V. Determinants of mortality from cystic fibrosis in Canada, 1970-1989. Am J Epidemiol. 1996 143 (10): 1007-17.

Claims

CLAIMSHaving therefore specifically described and determined the nature of this invention and the manner in which the same must be put into practice, the following is claimed as proprietary and exclusive right:

1. A high calorie, easily digestible food product, comprising a component of high fat content and at least one digestive enzyme selected from the group consisting of enzymes with lipolytic activity, enzymes with proteolytic activity, enzymes with amylolytic activity, and mixtures thereof.

2. The food product of claim 1, wherein the high calorie component is selected from fats, carbohydrates, proteins and combinations thereof.

3. The food product of claim 2, wherein the fats are selected from the group consisting of:

Lard;

Fats of animal origin;

Margarine;

Hydrogenated fats of synthetic origin; Cocoa butter;

Peanut butter;

Fats of vegetable origin;

Saturated fatty acids;

Unsaturated fatty acids; By-products of the same; and

Mixtures of the same.

4. The food product of claim 3, wherein the said fatty substance is peanut butter paste.

5. The food product of claim 3, wherein the fatty substance is cocoa butter.

6. The food product of claim 3, wherein said fatty substance is between 10% and 70% by weight of the wet weight of the food product.

7. The food product of claim 1, wherein said enzymes are of an animal origin.

8. The food product of claim 7, wherein said enzymes of animal origin are selected from the group consisting of:

Porcine pancreatine;

Bovine pancreatine;

Porcine pancrelipase; Bovine pancrelipase;

Lipase from animal origin;

Trypsin of animal origin;

Amylase of animal origin;

Proteases of animal origin; Phospholipases of animal origin; and

Nucleases of animal origin.

9. The food product of claim 1, wherein said enzymes are of microbial origin.

10. The food product of claim 9, wherein said enzymes of a microbial origin are selected from the group consisting of:

Lipase of microbial origin; Trypsin of microbial origin; Amylase of microbial origin;

Lactase of microbial origin; Beta-galactosidase of microbial origin; Proteases of microbial origin; Phospholipases of microbial origin; and Nucleases of animal origin.

11. The food product of claim 1 , wherein said enzymes are of biotechnological origin.

12. The food product of claim 11, wherein said enzymes of biotechnological origin, are selected from the group consisting of: Lactase synthesized using genetic engineering;

Beta galactosidase synthesized using genetic engineering;

Lipase synthesized using genetic engineering;

Amylase synthesized using genetic engineering;

Trypsin synthesized using genetic engineering; Proteases synthesized using genetic engineering;

Phospholipases synthesized using genetic engineering; and

Nucleases synthesized using genetic engineering.

13. The food product of claim 1, wherein said enzymes are selected from the pancreatine group.

14. The food product of claim 1, wherein said enzyme has an activity of between 400 and 2,000 international units of enzymatic activity per gram of fat.

15. The food product of claim 14, wherein said enzyme has an activity of

1,000 international units of enzymatic activity per gram of fat included in each food ration.

16. The food product of claim 1, wherein the enzymes are protected by an enteric coating.

17. The food product of claim 16, wherein said enteric coating is a complex polymer.

18. The food product of claim 16, said enteric coating has its shape selected from the group consisting of tablets, minitablets, microcapsules, microspheres, minimicrospheres, pellets, minipellets, minitablets, and microtablets.

19. The food product of claim 2, wherein said proteins are selected from the group consisting of: Whey;

Powdered whole milk;

Powdered nonfat milk;

Vegetable proteins;

Soy proteins; Ovalbumin;

Lactoalbumin;

Albumin;

Gluten;

Proteins and synthetic polypeptides; By-products of the above; and mixtures thereof.

20. The food product of claim 2, wherein said proteins are between 10% and 70% by weight of the wet weight of the food product.

21. The food product of claim 2, wherein said carbohydrates are selected from the group consisting of:

Sucrose;

Lactose; Maltose;

Maltodextrins; Fructose; Complex polysaccharides;

Starch;

Glycogen;

Vegetable syrups; Corn syrup;

Insulin;

Pectin;

Dextrose;

Alginate; Agar;

Cellulose;

Carboxymethyl cellulose;

Fructo-oligosaccharides;

Honey; By-products of the above; and

Mixtures of the same.

22. The food product of claim 2, wherein said carbohydrates are between 10% and 70% by weight of the wet weight of the food product.

23. The food product of claim 1, wherein further comprising nutrients selected from the group consisting of:

Vitamins; Fibers; Trace elements;

Substances with therapeutic activity; and Substances with pharmacological activity.

24. The food product of claim 1, specified because it is supplemented with flavorings and preservatives.

25. The food product of claim 1, in one or more of the following forms: solids, semisolids, cream, paste, powder, solid bars, ice cream.

26. A method of preparation of the food product of in claiml, specified because it includes the following steps:

Heating a mixture of high fructose syrup and fat substance to 40° C until it is blended into the fat substance;

Adding semi-solid peanut butter to fat substance liquefied in the prior step;

Mixing with a low-speed mixer; Breaking up the sugar enzymes and powdered milk;

Adding powdered sugar enzymes and milk slowly to the mixture in the mixer; and

Mixing everything in a low-speed mixer for 15 minutes until a final soft and homogenous mixture is obtained.

27. A method of preparation of the food product of claim 25, further comprising the steps: pouring the soft, homogenous mix into a metallic mold and cooling the product.