United States Patent:   6,008,027

Appl. No.:  896210

A lactase-containing preparation is prepared for use by mammals having a lactase deficiency. A dried bacterial culture containing lactase is mixed with a desiccant such as silicon oxide to stabilize water content of the dried culture. A unit dosage of the resultant stabilized dried bacterial culture is encapsulated in an ingestible capsule such as gelatin capsule. The capsule is coated with an enteric polymer, and the coated capsule is treated under vacuum pressure to remove oxygen and moisture. The treated coated capsule has an extended shelf-life at room and elevated temperatures, and provides lactase activity for at least 10 hours after ingestion. The dried bacterial culture may be in freeze dried form. Suitable bacterial cultures are Lactobacillus acidophillus, Lactobacillus bulgaricus and Streptococcus thermophilus.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

In accordance with the present invention a lactase replacement preparation in the form of a capsule that is readily ingestible by a human or animal and which is available to provide the desired lactase replacement for extended periods of time after ingestion, e.g., for at least ten hours and preferably to about twenty-four hours is provided. The lactase replacement capsule of the present invention is formed by using bacterial/fungal cultures, including, for example, Lactobacillus acidophillus, Lactobacillus bulgaricus, and Streptococcus thermophilus supplied in freeze dried colony form. The bacterial culture in powder form is mixed with stabilizing dessicants such as silicon oxide, silicon dioxide, microcrystalline cellulose, or redried starches and loaded in unit dosage gelatin capsules. The gelatin capsules are then banded and sealed with an aqueous enteric polymer coat using known capsule coating technique, such as an aromatic fluid bed coating, with a known polymer coating suspension such as Eudragit. The capsule is then placed in a chamber under a vacuum of approximately 55-70 microns for 24 to 144 hours, and preferably for 72 hours, using a vacuum pump.

The manufacture of the lactase replacement of the invention in unit dosage capsule form, using L. acidophillus as an example, will now be described. L. aciclophillus supplied in a freeze dried colony form containing an amount in the range of from about 50% weight percent to about 100% weight percent and preferably from about 90% weight percent to about 95% weight percent is mixed with silicon dioxide in proportions to provide from about 95% volume of L. acidophillus in a 250 mg capsule (minimum concentration about 250,000) mixed with 5% silicon dioxide. The encapsulated mixture is sealed with an aqueous enteric polymer coating using an Eudragit polymer. The capsule is then placed in a vacuum chamber at about 55-70 microns for seventy-two hours using a vacuum pump, thereby removing oxygen and moisture from the capsule.

Various experiments conducted where capsules were formed and enterically coated but not subjected to vacuum treatment to remove moisture resulted in capsules that did not survive at elevated temperatures (35^oC. or higher) for extended periods. When desiccants were used along with vacuum suctioning, enzyme activity capsules survived elevated temperature (35^oC.) and moisture levels for periods as long as 18 months, and even longer. Furthermore, it was found that using Eudragit for the enteric coat had several advantages over using other types of polymers for the coating. For example, this coating could be applied at low temperatures, such as 25^oC., and it was possible to eliminate the use of the opadry coating steps typically used before. The elimination of these steps speeds the coating process, allowing less heat exposure per unit time.

The lactase replacement composition of the present invention also overcomes the disadvantages of currently available lactase replacement products in two significant ways. First, the capsule of the present invention provides a capsule form of replacement that has long acting capability after ingestion by preventing premature release of the bacterial culture. Secondly, the capsule provides an increased shelf life.

First of all, the lactase replacement capsule of the invention by utilizing a combination of desiccant within a capsule in conjunction with an enteric coating is sturdy enough to prevent stomach acid, such as hydrochloric acid, from destroying the capsule and prematurely releasing the bacterial culture. Once the capsule is opened in an elevated alkaline environment, e.g., the alkalinity of the small bowel, the culture is able to "implant" itself onto the small bowel, proliferate, and produce continual lactase replacement activity for the consumer for approximately 24 hours. Moreover, because the bacteria replacement capsule of the invention is capable of withstanding gastric acids and getting into the small intestine without destruction, the bacterial culture is present after 3-5 days from ingestion and is able to continue to produce lactase enzyme for the 3-5 days without the need for the individual to consume additional cultures. In general, individual serving size will initially require two capsules in the morning and two capsules ten hours later for seven days. After the seven days, the individual will require one to two capsules every twenty-four hours, depending upon the degree of lactose intolerance.

The cumulative effect of these microorganisms is to control the composition and metabolic activity of the intestinal microflora. This optimum balance has been associated with good nutrition and health. These organisms produce antibiotics, lower pH, promote oxidation reduction augmenting antimicrobial actions, and deconjugate bile acids in the intestinal tract exerting an influence on the presence of other types of bacteria. Studies indicate a cholesterol lowering property for coronary artery disease and biodegradation of nitrates implicated as a causative factor in colon cancer.

Secondly, the shelf life of the capsules is increased as a result of the use of drying agents, highly concentrated bacterial colony count, and exposure of the capsules to vacuum pressure over a set period of time. Variables resulting in the premature death of most bacterial cultures include elevated temperatures, low pH, elevated pressures, and elevated moisture levels. Small changes in moisture and temperature appear to be the most deleterious. In the present invention, the capsules have been found to withstand elevated temperatures, such as 35^oC., and moisture levels as a result of the combination of the drying agent, high concentration of bacterial culture, and exposure to vacuum pressure. Therefore, the previous ineffectiveness of the bacterial culture after three to six months of shelf life, has been prolonged to eighteen months at room temperature and to four months at continuous elevated temperatures and to four months at continuous elevated temperatures and moisture. Competitive products have a 100% death rate after 24 hours at this elevated temperature.

Claim 1 of 8 Claims

1. A preparation containing lactase for supplying lactase to mammals having a lactase deficiency which comprises:

an encapsulated stabilized dried bacterial culture containing lactase of a unit dosage amount having a bacterial colony count of at least 250,000, said stabilized dried bacterial culture being a mixture of a dried bacterial culture containing lactase and an amount of a desiccant sufficient to stabilize water content of the dried bacterial culture, said encapsulated stabilized dried bacterial culture being sealed with a polymeric enteric coating and treated under vacuum for a time sufficient to substantially remove oxygen and moisture content thereof and provide desired lactase activity for at least about 10 hours after ingestion.

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