Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Food or edible as carrier for pharmaceutical
Reexamination Certificate
2001-06-08
2003-09-16
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Food or edible as carrier for pharmaceutical
C424S400000, C424S600000, C426S601000
Reexamination Certificate
active
06620427
ABSTRACT:
The present invention relates to a method for increasing bone mineralization in a pediatric population. Other aspects of the invention relate to methods for improving the nutritional status of infants and toddlers.
BACKGROUND
Bone serves an important physiologic role. It provides mechanical strength. All of the bones collectively, need to be strong enough to support the entire weight of the body, and any additional mechanical burden. It is widely accepted that bone mineral content and density, are directly correlated with the mechanical strength of the bone.
Bone is composed primarily of matrix proteins and calcium salts. Bone growth involves not only an increase in bone size, but an increase in the amount of such components as well. Bone growth is controlled by osteoblasts. These osteoblasts adhere to the terminal portion of existing bone and secrete bone matrix proteins, which differentiate into bone cells (osteocytes) and become part of the tissue of the bone. These osteoid tissues are then mineralized, primarily by calcium and phosphorus. The mineralization gives the bone its mechanical strength and allows it to serve its physiologic role. Substantial bone growth continues for up to the first 20 years of life.
However, after age 35, bone mass and mineral content begin declining gradually reducing the strength of the bone tissue. Consequently, when mechanical strength declines to a certain level, the individual is at greater risk of bone fracture. This is often referred to as osteoporosis.
Medical research has focused on ways of preventing the occurrence of osteoporosis. This research has shown that one of the most effective means of preventing osteoporosis is the establishment of a high bone mass during the childhood years. The establishment of significant bone mass allows a greater loss of bone before osteoporosis becomes problematic. Investigators have started to study childhood diets and their impact on bone formation. Consumption of calcium is an important dietary variable in promoting the development of substantial bone mass in the individual.
Part of this research has examined what impact, if any, infant formula has on bone development. Nelson et al, Journal of the American College of Nutrition, Vol. 17, No. 4, 327-332 (1998), evaluated whether the fatty acid content of infant formula impacted calcium absorption. Nelson et al determined that oil blends did have an impact on calcium absorption. Nelson et al found that the presence of palm olein oil reduced calcium absorption by approximately 35%, when compared to formula which did not contain palm olein oil. The authors concluded that this reduced calcium absorption was unlikely to have any significant physiologic impact on the infant, including bone mineralization. The authors stated that the most likely adverse effect is constipation in the infant.
Nelson et al also evaluated the impact of palm olein on calcium absorption in a different group of infants Am J Clin Nutr 1996;64:291-6 (1996). The results obtained in this study were consistent with the results described by Nelson et al supra. Infants consuming formula containing palm olein oil had lower rates of calcium absorption. The authors emphasized that the clinical significance of such reduced absorption is unknown.
Motil commented on the work of Nelson et al supra, in the Journal of the American College of Nutrition, Vol. 17, No. 4, 303-305 (1998). Motil reiterated that Nelson et al had documented that infants consuming palm olein oil had lower relative calcium absorption, when compared to a group of infants consuming alternative fats. However Motil emphasized that these findings were insignificant from a clinical standpoint. Motil emphasized that calcium homeostasis is a highly regulated process and is not dependent solely upon the amount of calcium that is absorbed. Further, infants in the palm olein group were receiving 100 mg/day of calcium, which is the established RDA. Thus, a fair reading of Motil is that the presence of palm olein is expected to have no impact upon the rate of bone mass development in an infant.
Kennedy et al evaluated an infant formula which contained a synthetic triglyceride (STG) Am J Clin Nutr 1999:70:920-7. This STG contained palmitic acid in the sn-2 position of the glycerol nucleus (i.e. the center carbon atom). This STG is structurally similar to the triglyceride contained in human breast milk. An infant formula containing this STG was compared against a formula containing triglycerides, in which the palmitic acid was contained primarily in the 1- and 3-positions of the glycerol nucleus. These triglycerides are typically contained in infant formula and are obtained from vegetable oils. Kennedy et al evaluated growth rates, fat absorption, and bone mineralization of the two groups. Similar parameters were observed in a group of infants consuming breast milk. Kennedy found that infants consuming the STG had rates of bone mineralization comparable to the breast fed group. Infants receiving the triglycerides obtained from vegetable oils had lower rates of bone mineralization than infants consuming the STG.
Kennedy noted that enhanced calcium absorption had previously been observed with formulae having reduced palmitate content. However, the fatty acid profile of such formula differs substantially from that of breast milk and therefore caution should exercised in its consumption. Kennedy emphasized that palmitic acid is the predominant fatty acid in human milk and the clinical significance of omitting this fatty acid needs further study.
Thus while the prior art clearly establishes that palmitic acid frombovine and vegetable sources negatively impacts the absorption of calcium, the clinical significance of this finding is unknown. Numerous authors agree that the impact of this finding on bone mass is unknown, but probably is clinically insignificant. Other authors suggest caution in the utilization of low palmitic acid formula since it's fatty acid profile differs so significantly from human milk.
SUMMARY OF THE INVENTION
In accordance with the present invention, it has been discovered that it is possible to enhance bone mass accretion in an infant or toddler. This increased bone mass can be accomplished by enterally feeding the juvenile a formula containing a source of calcium and a source of fat, in which the fatty acid profile is characterized by having a palmitic acid content of about 19 w/w %, or less. Such a feeding regimen will result in an enhanced rate of bone mineralization and ultimately enhanced skeletal strength.
The pediatric formula utilized in the method of the present invention will typically be an infant formula. It should contain sufficient nutrients to promote the growth and development of the juvenile. It typically will contain protein, carbohydrate, vitamins, and minerals, as is known in the art. The formula will contain calcium as is known in the art. The key to the invention is the utilization of a fat blend that is low in palmitic acid. While the prior art demonstrates that palmitic acid interferes with the absorption of calcium, the enclosed human clinical studies demonstrate that diminished absorption is associated with decreased levels of bone mass in a human infant. Such a finding contradicts the teachings of the prior art, which taught that this diminished calcium absorption had no clinical significance on bone mass accretion.
The fat blend utilized in the pediatric formula of the present invention must be low in palmitic acid, but yet contain sufficient fatty acids to support optimal infant growth and development. This may be accomplished by a blend having a fatty acid profile characterized by about 9.5-21 weight % lauric acid, about 19 weight %, or less, palmitic acid, and about 34-48 weight % oleic acid. In a further embodiment, palmitic acid content is maintained at about 15 weight %, or less, and often at about 10 weight %, or less. In an additional embodiment, the oil blend may additionally contain about 2.7-3.1 w/w % of stearic acid, about 17-29 w/w % of linoleic acid and about 1.7-3.2 w/w %
Benson John D.
Lasekan John B.
Masor Marc L.
Montalto Michael B.
Abbott Laboratories
Brainard Thomas D.
Evans Charesse
Page Thurman K.
Winter William J.
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