Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Food or edible as carrier for pharmaceutical
Reexamination Certificate
2000-09-25
2001-06-26
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
C424S464000, C424S451000, C424S484000, C424S486000, C424S489000, C424S466000, C424S501000, C424S738000, C514S772400
Reexamination Certificate
active
06251421
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to pharmaceutical compositions containing an inhibitor of gastrointestinal lipase, and at least one compound selected from the group consisting of psyllium husk, its derivatives and salts thereof.
Psyllium husk, has a long history of use in traditional and herbal medicine and has been in use in the United States over 60 years ago. Psyllium husk is derived from the seed or leaves of the
Plantago ovata
plant. Besides
Plantago ovata
, psyllium is also known as Ispaghula and Ispagol.
Plantago ovata
is an annual herb native to Asia, the Mediterranean region, and North Africa. Psyllium grows in sand and silty soils. Currently, psyllium is extensively cultivated in India and Pakistan. India provides about 85% of the psyllium available in the world market. The US is the world's largest importer of psyllium husk. Psyllium has a long history of use through the world and has been used in traditional medicine in the United States, Europe, India, and China. Some of the uses of psyllium in traditional medicine are as laxative, emollient, demulcent, and diuretic.
Currently in the United States, psyllium husk is most often used as a bulk fiber laxative, in foods or in various fiber supplements. In 1998, the Food and Drug Administration (FDA) authorized the use in a health claim in the labeling of foods and dietary supplements containing psyllium husk. The health claim may state that diets low in saturated fat and cholesterol that include 7 grams of soluble fiber per day from psyllium may reduce the risk of heart disease by lowering cholesterol levels in the blood.
Psyllium is a bulk forming fiber. Other fibers that belong to the class of bulk forming fibers are cellulose, methylcellulose, sodium carboxymethylcellulose, karaya, malt soup extract, polycarbophil, and wheat bran. Bulk forming fibers are laxatives because of their water holding properties. They exert their action primarily through mechanical effects by bulking the colonic contents and shortening transit time.
Anal leakage of oil (oily spotting) is an adverse effect which is occasionally observed in patients treated with lipase inhibitors. It results from physical separation of some liquid unabsorbed dietary fat from the bulk of the fecal mass in the lower large intestine.
SUMMARY OF THE INVENTION
It has now been found that by combining a lipase inhibitor with effective amounts of psyllium, psyllium husk or the seeds or leaves thereof, the phenomenon of anal leakage of oil can be strongly reduced. The present invention is directed to pharmaceutical compositions containing an effective amount of an inhibitor of gastrointestinal lipase, and an effective amount of at least one compound selected from the group consisting of psyllium fiber or husk, its derivatives and salts thereof. The compositions of the present invention also optionally include auxiliary excipients.
The present invention is also concerned with the use of psyllium, psyllium husk or the seeds or leaves thereof for the combined simultaneous, separate or chronologically spaced use with an inhibitor of gastrointestinal lipase, such as orlistat or Pluronic L101, in the treatment of obesity and hyperlipaemia and their comorbidities, such as type II diabetes mellitus.
Artificial non-absorbed fats, mostly sucrose polyester, are used in the food industry for the production of low fat foods, such as low fat potato chips, low fat cookies, low fat salad dressings and low fat ice cream. The ingestion of higher amounts of such foodstuffs containing non-absorbable fats can induce oily leakage.
The pharmaceutical compositions of the present invention reduce fat absorption through inhibition of gastrointestinal lipase. The invention is further concerned with the use of psyllium, psyllium husk or the seeds or leaves thereof for treating or preventing the syndrome of anal leakage of oil occurring after the administration of an inhibitor of gastrointestinal lipase, such as orlistat or Pluronic L101, or after ingestion of food containing poorly absorbable or non-absorbable fats or oils or of undigestible oily fat substitutes.
Methods are provided for treating or preventing the syndrome of anal leakage of oil in a patient to whom a composition containing an inhibitor of gastrointestinal lipase is orally administered in unit dosage form.
DETAILED DESCRIPTION OF THE, INVENTION
Examples of lipase inhibitors which can be used in the compositions of the present invention are orlistat or Pluronic L101, lipstatin, panclicins, hesperidin, ebelactones, esterastin and their derivatives, and valilactone or such natural compounds as
Cassia Nomame
. The most preferred lipase inhibitor is orlistat or Pluronic L101.
Orlistat reduces the absorption of dietary fat. Its use for the control or prevention of obesity and hyperlipaemia, is described in U.S. Pat. No. 4,598,089. Orlistat is an N-formyl-L-leucine ester with (3S,4S)-3-hexyl-4-[(2S)-2-hydroxytridecyl]-2-oxetanone. Its chemical structure is as follows:
Another example of gastrointestinal lipase inhibitor is Pluronic L101 which is a hydrophobic surface-active agent, and potent in-vitro inhibitor of human pancreatic lipase. When administered as a 1 percent or 3 percent dietary admix to meal-fed rats, pluronic L-101 produced a significant and dose-dependent decrease in body weight gain while not affecting food consumption. Excretion of dietary fat in the feces was enhanced significantly in a dose-dependent manner during Pluronic L-101 treatment.
Pluronic is a poloxamer, a nononionic surfactant, and a block copolymer of propyleneoxide and ethylene oxide. The propylene oxide block is sandwiched between two ethylene oxide blocks, as follows:
(HO—(CH
2
CH
2
O)
x
(CH
2
CH
3
CHO)
y
(CH
2
CH
2
O)
z
—H
where x,z=2-128 y=16-67
In Pluronic L101, x, z=7; y=54
Any conventional auxiliary excipients can be used in formulating the dosage forms of the present invention. Examples of auxiliary excipients which can be used in the pharmaceutical compositions of the invention are binders, dilutens and lubricants, such as AVICEL, polyvinyl pyrrolidone (povidone), talc and sodium stearyl fumarate; sweeteners, such as sorbitol, glucose, saccharose, saccharine-sodium salt and sodium cyclamate; flavor agents, such as passion fruit, citron and limette; flavor enhancers, such as citric acid, monosodium citrate, sodium chloride and chinine sulfate; effervescing agents, such as sodium bicarbonate and tartaric acid, disintegrants, antimicrobial agents, such as p-hydroxybenzoic acid methyl or propyl ester; detergents and coloring agents, such as beta-carotene.
The experiment for loss of free fecal oil is based on the observation that mice, due to steadily grooming their furs, distribute any excreted free fecal oil all over their bodies. This results in an easily visible brownish coloring of the fur (oily fur greasing). In mice weighing 20-25 g, excretion of free oil is provoked by administering an excessive dose of orlistat or Pluronic L101 (300 .mu.mol/kg/day) together with a diet containing 7% fat, resulting in a daily fat intake of 1 g/day. The diet consists of mashed Hamburger, butter, French fries and string beans. When the diet contained psyllium, the extent of oily fur greasing is reduced, when compared to controls.
The compositions of the present invention reduce fat absorption in a patient through the use of a gastrointestinal lipase inhibitor to inhibit gastrointestinal lipase. The compositions also treat and prevent the syndrome of anal leakage of oil that can occur in a patient upon administration of the gastrointestinal lipase inhibitor. The compositions of the invention contain from 10 to 50, preferably from 20 to 40, parts by weight of psyllium, psyllium husk, seeds or leaves from 10 to 200, preferably from 20 to 80, parts by weight of auxiliary excipients for 1 part by weight of an inhibitor of gastrointestinal lipase, such as orlistat or Pluronic L101. The inhibitor of gastrointestinal lipase in the compositions of the invention is present in an amount at leas
Bennett Rachel M.
Page Thurman K.
Welsh & Katz Ltd.
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