Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1986-02-28
1987-11-17
Brown, J. R.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
536 46, 536103, A61K 3173
Patent
active
047074728
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to cycloartenol ferulate/cyclodextrin complex.
BACKGROUND ART
It has been known that hardly water-soluble pharmaceuticals will be ineffectively absorbed through digestive tracts. It is important to elevate the dissolution rate of these pharmaceuticals in order to improve these absorption through digestive tracts. Therefore it has been attempted to elevate the dissolution rate of hardly water-soluble pharmaceuticals to thereby improve the absorption of the same.
On the other hand, it is believed that cycloartenol ferulate, which is a component of .gamma.-oryzanol, has antiarteriosclerotic, gonadotropic and antioxidant effects and is effective in treating various diseases including autonomic imbalance, hypertension and hepatic disorder.
However it is very difficult to isolate cycloartenol ferulate in high purity from .gamma.-oryzanol. Further since cycloartenol ferulate is insoluble in water, it is ineffectively absorbed through digestive tracts and hardly transfers into blood when orally administered.
Thus it is believed that cycloartenol ferulate will insufficiently exert its pharmacological and physiological effects when administered alone or as a component of .gamma.-oryzanol.
DISCLOSURE OF THE INVENTION
It is an object of the present invention to overcome the above problem that cycloartenol ferulate is hardly soluble in water so that it is ineffectively absorbed through digestive tracts and exerts its pharmacological and physiological effects insufficiently, by improving the absorption of the same through digestive tracts to thereby elevate its pharmacological and physiological effects.
As a result of our studies, we have confirmed the formation of a complex of cycloartenol ferulate with cyclodextrin. We have further found that the formation of said complex will elevate the dissolution rate of cycloartenol ferulate and improve the absorption of the same through digestive tracts in animal tests, thus completing the present invention.
Accordingly the present invention relates to a cycloartenol ferulate/cyclodextrin complex which comprises cycloartenol ferulate included with cyclodextrin.
Cycloartenol ferulate as mentioned herein may be isolated from .gamma.-oryzanol and purified, e.g., in the following manner.
That is, 500 g of .gamma.-oryzanol is dissolved in 1.5 to 2.0 l of heated chloroform and methanol is added thereto until crystals separate out. The mixture is heated again to thereby dissolve the crystals and then allowed to stand at room temperature. Thus crystals separate out. The crystals thus obtained are washed with n-hexane. 100 g of the resulting crude cycloartenol ferulate is dissolved in chloroform, absorbed by a reverse phase column packing and developed with methanol/chloroform/water at a volume ratio of 6:2:1. Main fractions are combined and the solvent is distilled off therefrom. The residue is recrystallized from chloroform/methanol at a volume ratio of 1:1 to thereby give 60 g of cycloartenol ferulate.
Cycloartenol ferulate thus obtained is identified by high-performance liquid chromatography (HPLC), mass spectrometry (MS), infrared spectroscopy (IR) and nuclear magnetic resonance spectroscopy (NMR).
Thus its HPLC shows a single peak as shown in FIG. 1.
Its MS shows a molecular ion peak (602) of cycloartenol ferulate as shown in FIG. 2.
Its IR shows a streching vibration of C.dbd.0 at 1670 cm.sup.-1, vibrations of methyl groups at 1470 cm.sup.-1 to 1430 cm.sup.-1 and at 1380.sup.-1 to 1350 cm.sup.-1 and characteristic vibration pattern of a cyclopropane ring at 1020 cm.sup.-1 as shown in FIG. 3. Its NMR shows signals of a cyclopropane ring, an --OCH.sub.3 group, a hydroxyl group of phenol and ##STR1## at .delta. values of 0.58 ppm, 3.92 ppm, 5.92 ppm, and 6.15 ppm and 7.47 ppm, respectively as shown in FIG. 4. Furthermore it shows a signal of ##STR2## at 6.93 ppm.
These results prove that the product is cycloartenol ferulate.
Available cyclodextrins include .alpha.-cyclodextrin, .beta.-cyclodextrin, .gamma.-cyclodextrin, 2,6-di-O-methyl-.b
REFERENCES:
patent: 4352793 (1982-10-01), Yamahira et al.
patent: 4407795 (1983-10-01), Nicolau et al.
Aikawa Hiroyasu
Aoki Hidemi
Inagaki Tetsuya
Takahashi Masao
Brown J. R.
Peselev Elli
ZEria Shinyaku Kogyo Kabushiki Kaisha
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