Drug – bio-affecting and body treating compositions – Enzyme or coenzyme containing – Hydrolases
Reexamination Certificate
1995-06-06
2002-08-06
Witz, Jean C. (Department: 1651)
Drug, bio-affecting and body treating compositions
Enzyme or coenzyme containing
Hydrolases
C424S094610
Reexamination Certificate
active
06428786
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a composition and method for the enzymatic hydrolysis of lactose and, more particularly, to treating and controlling the symptoms of lactose intolerance.
BACKGROUND OF THE INVENTION
The human digestive system uses a series of enzymes to break down complex foods into simple molecules that can be absorbed by the body. Milk products contain lactose, which, when hydrolyzed, yield glucose and galactose. This hydrolysis is enzymatically catalyzed by lactase or &bgr;-D-galactosidase.
Decreased or non-existent intestinal lactase activity, known as lactose intolerance, is a deficiency that appears in pediatric, adolescent and adult populations. The inability to hydrolyze lactose into its component sugars results in bloating, cramping, abdominal pain, or flatulence after the ingestion of milk or dairy products. In severe cases, malabsorption resulting from lactose intolerance may result in anorexia and weight loss.
Lactose intolerance in humans can be treated in several ways. Prehydrolyzed milk and dairy products, having significantly reduced levels of lactose, are commercially available. Supplements in the form of fungal or yeast-derived lactases that are added to lactose-containing liquids are also available. The lactose may also be in the form of a tablet, which is ingested immediately before the consumption of milk products. Orally administrable tablets containing lactase derived from
Aspergillus oryzae
are available from Lactaid, Inc., Pleasantville, N.J.
A variety of factors influence the effectiveness of lactase-containing tablets in lactose intolerant patients. Tablets containing lactase derived from
Aspergillus oryzae
are intended to hydrolyze lactose in the acidic environment of the stomach. The empty stomach of a healthy human has a pH of 3 or less, but upon the ingestion of food, rises to about 5 or 6. Merki, H. S. et al., “Pattern of 24 Hour Intragastric Acidity in Active Duodenal Ulcer Disease and in Healthy Controls”,
Gut,
29, pp. 1583-87 (1988). Lactases derived from
Asperaillus oryzae
have an optimum pH of approximately 5, and are therefore suitable for the hydrolysis of lactose in the stomach environment. Gekas, V. et al., “Hydrolysis of Lactose: A Literature Review”,
Process Biochem,
20(1), pp. 2-12 (1985).
If a tablet containing lactase derived from
Aspergillus oryzae
is ingested too far in advance of the consumption of lactose-containing food, the lactase may be passed into the more neutral environment of the intestines, having a pH between about 6 and 8. Since the acid-active lactase is relatively inactive in this environment, the lactose may not be enzymatically hydrolyzed, and the symptoms of lactose intolerance may appear. Even if the lactase-containing tablet is ingested at the optimum time before a meal, if a sufficiently large amount of lactose-containing food products is consumed, some undigested lactose may pass to the intestines, resulting in discomfort in the lactose-intolerant patient.
Advances in medicine have increased the life expectancy of the Western world population. The elderly tend to have more neutral stomach pH due to the increase incidence of achlorhydria. There is also an increase in the use of H
2
blockers, which results in a more neutral stomach pH. As a result of these trends, the pH profile of the stomach environment for a significant portion of the population is moving out of the optimal range for enzymes derived from
Aspergillus oryzae.
A need, therefore, exists for a composition which in addition to hydrolyzing lactose under the normal acidic conditions found in a healthy stomach, has enzymatic activity in the more neutral environment of the intestines and in the stomachs of the elderly and users of H
2
blockers.
SUMMARY OF THE INVENTION
The present invention provides a composition for the enzymatic hydrolysis of lactose. This composition contains a first, active lactase having a first optimum pH range and a second, active lactase having a second optimum pH range. The first and second optimum pH ranges are of a different magnitude, which enables the composition to enzymatically hydrolyze lactose in environments having different or varying pHs. In a preferred embodiment, the first optimum pH range is about pH 3.0 to about pH 6.0, while the second optimum pH range is about pH 6.0 to about pH 8.0. A process for enzymatically hydrolyzing lactose using the first and second active lactases is also included in the present invention.
In a further embodiment of the present invention, a composition for treating or controlling the symptoms of lactose intolerance is provided. This composition contains a first lactase having an optimum pH range corresponding to the pH of the stomach environment and a second lactase having an optimum pH range corresponding to the pH of the intestinal environment. The composition may further contain a pharmaceutically acceptable, orally administrable carrier material. A method for treating or controlling the symptoms of lactose intolerance using the aforementioned composition is also disclosed.
The compositions and methods of the present invention provide for the enzymatic hydrolysis of lactose under the acidic conditions found in a healthy, human stomach as well as in the more neutral conditions of the intestines and stomachs of H
2
blocker users and the elderly suffering from achlorhydria.
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Eisenhardt Peter F.
Smith Leonard P.
Mc-Neil-PPC, Inc.
Witz Jean C.
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