DESCRIPTION
COMPOSITIONS AND METHODS FOR NUTRIENT DELIVERY
TECHNICAL FIELD
[0001] The present disclosure relates to improved enteral nutritional compositions
ซึ่งประกอบรวมด้วย docosahexaenoic acid ("DHA") and arachidonic acid ("ARA") and also to methods for providing nutritional support in the form of a stabilized emulsion to a population of subjects suffering from nutritional deficiencies, such as preterm and/or low-birth-weight infants. The liquid nutritional composition of the present disclosure may contain a lipid component that contains an emulsion of DHA and/or ARA that is dispersed in an เอเควียส component.
[0002] The nutritional composition may be suitable for enteral delivery via nasogastric tube, intragastric feeding, transpyloric administration and/or any other means of administration that results in the introduction of the nutritional composition directly into the digestive tract of a subject.
BACKGROUND ART
[0003] The present disclosure relates to an improved enteral nutritional composition that addresses nutritional deficiencies in ill populations as well as other physiological consequences often arising from those deficiencies. In particular, the disclosure addresses nutritional
deficiencies that may arise in preterm and/or low-birth-weight infants.
[0004] Nutritional support for a preterm infant is of great importance since short-term survival and long-term growth and development are at stake. Important goals when providing nutritional support to preterm infants include promoting growth rates and nutrient accretion, thereby optimizing neurodevelopmental outcomes and laying strong foundations for long-term health. These goals are not easily attained in a low-birth-weight infant, as often the premature infant may be critically ill and cannot tolerate traditional enteral feeding due to a variety of
factors ที่รวมถึง concomitant pathologies, immature gastrointestinal system, and other
immature organ systems.
[0005] Often, total parenteral nutrition ("TPN") is indicated as either the only or the preferred method of providing nutrition support for preterm infants. However, although TPN can be life saving, it is not a perfect means of nutritional support. Traditionally, nutritional
compositions administered as part of the TPN regimen lack many critical nutrients, which may induce long-lasting physiological and developmental consequences for preterm infants.
[0006] Low-birth-weight and very-low-birth-weight infants are particularly susceptible to both postnatal growth failure and nutrient deficiencies. Yet, TPN fails to provide an adequate supply of valuable nutrients, such as DHA and ARA. Accordingly, many preterm infants do not receive an adequate supply of DHA or ARA.
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[0007] In healthy subjects consuming a normal diet, โดยที่ the normal diet provides sufficient DHA and ARA, there is generally no need for DHA or ARA supplementation.
Consuming a certain amount of DHA nad ARA as an infant is important because considerable amounts of both DHA and ARA are deposited in the human brain and other tissues during intrauterine and postnatal growth. (Clandinin MT et al., Requirements of newborn infants for long chain polyunsaturated fatty acids. Acta Paediatr Scand 1989; 351 Suppl: 63-71.) In fact, the fetus accumulates long chain polyunsaturated fatty acids ("LCPUFAs") such as DHA and ARA during the last trimester of pregnancy, as the placenta provides the fetus with DHA and ARA. (A. Lapitlonne et. Al, Reevaluation of the DHA requirement for the premature infant. Prostaglandins, Leukotrienes and Essential Fatty Acids 81 (2009) 143-150.) But in cases of preterm birth, an infant faces the sudden loss of the placental LCPUFA supply. Accordingly, premature infants may rapidly exhaust their available LCPUFA stores, and the resulting
LCPUFA deficit may increase the more premature the infant.
[0008] Meeting the nutritional needs of preterm infants is problematic due to their
gastrointestinal immaturity, poor nutrient stores and the high demand for nutrients to support growth. (L.G. Smithers et al., Effect of two doses of docosahexaenoic acid in the diet of
preterm infants on infant fatty acid status: Results from the DINO trial. Prostaglandins,
Leukotrienes and Essential Fatty Acids 79 (2008) 141-146.) Yet, in critically ill, preterm infants, it appears that an inadequate supply of essential fatty acids and their derivatives may lead to long-term impairments in visual function and in neurodevelopment. (D. Driscoll et al.,
Pharmaceutical and clinical aspects of parenteral lipid emulsions in neonatology. Clinical
Nutrition (2008) 27, 497-503.) These problems are exacerbated by the absence of LCPUFAs, such as DHA and ARA, in parenteral and TPN nutritional compositions.
[0009] Indeed, TPN and other parenteral nutritional supplements that are currently on the market provide, at best, only negligible amounts of preformed DHA and ARA. DHA is an omega-3-fatty acid and is the most abundant LCPUFA in the brain and retina and is thought to be essential for proper brain and vision development of infants. Although a metabolic pathway exists for biosynthesis from dietary linolenic acid, the pathway is bioenergetically unfavorable, and mammals obtain most of their DHA from preformed DHA provided via dietary sources. For infants, then, the source of DHA is typically human milk; however, DHA is typically absent from parenteral formulas provided to preterm infants.
[0010] Parenteral formulas also generally fail to provide sufficient amounts of ARA. ARA is an omega-6 LCPUFA that serves a major role as a structural lipid associated with
phospholipids in the blood, liver, muscle and other major organ systems. ARA is synthesized by the elongation and desaturation of linoleic acid. However, most ARA must be provided in the diet. ARA is especially important during periods of rapid body growth, and is, therefore, an important component of infant nutrition.
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[0011] Numerous studies have indicated that unsupplemented preterm milk provided to infants provides inadequate quantities of several nutrients required to meet the needs of
preterm infants (Davis, D.P., "Adequacy of expressed breast milk for early growth of preterm infants", Archives of Disease in Childhood, 52, p. 296-301, 1997). While exact needs vary
among infants due to differences in activity, energy expenditure, efficiency of nutrient
absorptioh, illness and the ability to utilize energy for tissue synthesis, presently available
parenteral nutritional sources are inadequate.
[0012] Moreover, feeding volume is often not well tolerated in preterm infants, and nutrients must be provided in an acceptable volume, often via enteral administration. An
appropriate method of enteral feeding for a preterm infant is based on gestational age, birth weight, clinical condition and on the opinion of presiding medical personnel. Specific feeding decisions are made based on an infant's ability to coordinate sucking, swallowing and
breathing. Frequently, preterm infants or infants who are less mature, weak or critically ill require feeding by tube to avoid risks of aspiration and to conserve energy.
[0013] Nasogastric feedings are commonly used in neonatal intensive care units and may be accomplished with bolus or continuous infusions of fortified human milk or other
nutritional supplements. Continuous feedings may be better tolerated by very low birth weight infants and infants who have not previously tolerated bolus feedings; however, as previously discussed, reduced or deficient nutrient delivery is a problem associated with continuous
feeding methods known in the art.
[0014] Accordingly, there exists a need in the art to provide a nutritional composition ซึ่งประกอบรวมด้วย valuable nutrients that support infant development, such as DHA and ARA.
Therefore, the nutritional compositions and methods of the present disclosure provide enteral nutritional support to subjects suffering from nutritional deficiencies in order to promote
optimum health and development. The nutritional composition(s) disclosed herein deliver
important nutrients that are either absent from or provided in inadequate amounts in parenteral nutrition compositions and other infant formulas.
DISCLOSURE OF THE การประดิษฐ์
[0015] Briefly, therefore, the present disclosure is directed to a stable nutritional
composition for addressing nutritional deficiencies in subjects, such as preterm infants,
requiring small-volume nutritional support and to methods for promoting healthy development of those subjects. The present disclosure provides compositions for administering fatty acids, such as DHA and/or ARA and other nutrients to a subject in order to prevent development of nutritional deficiencies and/or to correct existing nutritional deficiencies.
[0016] In one embodiment, the present disclosure ประกอบรวมด้วย a nutritional composition, ซึ่งประกอบรวมด้วย an emulsion of DHA and/or ARA. In some embodiments, the nutritional
composition is appropriate for enteral administration in a pediatric subject.
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[0017] Yet another embodiment ประกอบรวมด้วย a nutritional supplement ซึ่งประกอบรวมด้วย DHA and/or ARA for fortifying human milk or infant formula suitable for oral administration.
[0018] In another embodiment, the present disclosure ประกอบรวมด้วย a method for providing
nutritional support to a subject, the method ซึ่งประกอบรวมด้วย administering to the subject a nutritional composition ซึ่งประกอบรวมด้วย an emulsion of DHA and/or ARA.
[0019] It is to be understood that both the foregoing general description and the
following detailed description present embodiments of the disclosure and are intended to
provide an overview or framework for understanding the nature and character of the disclosure