Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Reexamination Certificate
1998-03-26
2001-06-19
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
C424S489000, C424S491000, C424S494000
Reexamination Certificate
active
06248362
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a composite for delivering active ingredients ingested orally to the large intestine without elution of the ingredients from the composite before reaching the large intestine, and a process for delivering the active ingredients with use of the composite.
2. Background Art
Colon cancer is one of the most prevalent cancers in the western countries. Patients of colon cancer has recently been increased also in Japan with the change of eating habits into western style. It is believed that the crisis of colon cancer can be eliminated by dietary care. However, such care actually can be practiced only with difficulty, since it requires expert knowledge and practice over a long period. Moreover, the prophylaxis of colon cancer with medicines or foods requires the lasting administration of them, so that these medicines or foods are also required to have the safety corresponding to or higher than that of ordinary medicines.
In the meantime, the mechanism of occurrence of colon cancer has been gradually elucidated in these years. It is believed as one of the possible mechanism of oncogenesis that lipid peroxide generated by the catalytic action of iron cation in the large intestine results in the damage of genes, which promotes the canceration of cells. It is thus believed essential for the prophylaxis of cells. It is thus believed essential for the prophylaxis of colon cancer to transform the iron cation into an innocuous form.
One of the present inventors has studied numerous materials which have been ingested by human for a long period and has found that phytins occurring in a wide variety of foods and having epidemiologically and cytologically established availability effectively work for transform the iron cation into an innocuous form in the large intestine (Cereal Chemistry, 59(6),525,1982). Intense lipid peroxide suppressive activity of phytins based on the iron cation scavenging ability is the most important activity for the prophylaxis of colon cancer (Molecular Medicine, 33(4), 404 (1996)).
However, phytins are also known to have a mineral ingestion inhibitory effect, and it is indicated that phytins are harmful when ingested in a large amount. Thus, there is a need of a composite which can pass as an innocuous form through the upper part of the small intestine which is major site of absorbing minerals such as iron or calcium and then release phytins at the large intestine that phytins act on and are absorbed in.
There are also the ingredients in addition to phytins which are preferably delivered only to the large intestine, such as Lactobacillus bifidus, anti-oxidants, and peptides.
There have been described various forms of composites which make possible active ingredients to be delivered to the large intestine including for example those in the form of capsule (Japanese Patent Laid-Open Publication Nos. 41422/1992, 225922/1992, 179618/1994, and 327634/1995), those coated with monolayer (Japanese Patent Laid-Open Publication Nos. 368321/1992, and 2701/1995), and those coated with chitosan and a special polymer (Japanese Patent Laid-Open Publication Nos. 34927/1991, 69333/1992, and 217924/1992). However, all of these composites have problems to be solved.
There is still a need of composites which are safe even in their successive administrations for a long period and can deliver the orally administered an active ingredient to the large intestine without elution of the ingredients from the composite before reaching the aimed site.
SUMMARY OF THE INVENTION
The present inventors have found that a composite in which a core containing an active ingredient is coated with an internal layer containing chitosan, and then coated with an external layer comprising a gastric acid resistant material can deliver the active ingredient only to the large intestine, and thus accomplished the invention on the basis of such finding.
Thus, an object of the present invention is to provide a composite which is safe even in their successive administrations for a long period and can deliver the orally administered an active ingredient only to the large intestine without elution of the ingredients from the composite before reaching the large intestine.
Another object of the present invention is to provide a process for delivering an orally administered active ingredient only to the large intestine without elution of the ingredients from the composite before reaching the large intestine.
According to the present invention, there is provided a composite for delivering an active ingredient to the large intestine, and comprises the active ingredient, a core in which the active ingredients are contained, an internal layer comprising chitosan with which the core is coated, and an external layer comprising a gastric acid resistant material with which the internal layer is coated, wherein all of the materials in the composite have the empirically established safety to humans.
Furthermore, according to the present invention, there is provided a process for delivering an active ingredient only to the large intestine of animals, including humans, which comprises a step for administering orally a composite comprising a core in which the active ingredient is contained, an internal layer comprising chitosan with which the core is coated, and an external layer comprising a gastric acid resistant material with which the internal layer is coated to animals, including humans.
According to the present invention, there is provided a composite having a property that an active ingredient is not eluted at the stomach or the small intestine but eluted at the large intestine. Thus, it can deliver the active ingredient to the large intestine as the aimed site without contact of the active ingredients with the stomach or the small intestine.
The gastric acid resistant material of the external layer prevents chitosan from decomposing by gastric acid and the internal layer containing chitosan prevents the elution of the active ingredients in the core in the small intestine. Then, in the large intestine, chitosan is relaxed and decomposed by the invasion of water with the passage of time due to the effect of intestinal microorganisms and osmotic pressure, and thereby it is believed that the active ingredients are for the first time eluted in the large intestine.
Chitosan contained in the internal layer is a material which is compatible and non-toxic to organisms and has already been applied to many foods and cosmetics, and of which safety to humans have been proved. It is possible to obtain a composite which may be administered consecutively for a long period and has an extremely high safety by constituting the core, the ingredients other than chitosan in the internal layer and the external layer with materials have the established safety to humans. This is a major advantage of the present invention.
REFERENCES:
patent: 5846565 (1998-12-01), Brem et al.
patent: 0454383 A1 (1991-04-01), None
patent: 0466566 A2 (1991-07-01), None
Takizawa Toshio
Tominaga Shigeru
Yamada Masahiko
Benston, Jr. William E.
Meiji Seika Kaisha Ltd.
Page Thurman K.
Wenderoth , Lind & Ponack, L.L.P.
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