Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Reexamination Certificate
2002-10-21
2003-10-14
Krass, Frederick (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
C554S077000, C424S702000, C514S475000
Reexamination Certificate
active
06632837
ABSTRACT:
FIELD OF INVENTION
The invention relates to compositions of selenium monobromide-oil reaction product and further relates to pharmaceutical compositions containing these reaction products. Methods of making and using such compositions for treating the symptoms of neoplastic conditions are also encompassed.
BACKGROUND ART
The antitumoral and antineoplastic activity of selenium derivatives has already been described in earlier patents. For example, U.S. Pat. No. 4,564,634 discloses compositions of selenium incorporated in tung oil, while U.S. Pat. No. 4,681,753 discloses compositions of certain dialkyl diselenides and ketones.
These compositions are effective for the treatment of certain neoplastic conditions, but I have found that pharmaceutical compositions containing a selenium monobromide-oil reaction product in combination and preferably with epichlorohydrin provide improved performance and are effective in treating a wide range of neoplastic conditions.
SUMMARY OF THE INVENTION
The invention relates to a composition of selenium monobromide-oil reaction product useful in treating a subject suffering from neoplastic conditions. The selenium monobromide-oil reaction product typically exhibits ultraviolet absorption maxima typical of conjugated trienes and conjugated dienes. The reaction product comprises of selenium monobromide-in-oil which contains at least about 0.1 weight percent of selenium monobromide, prepared from an oil containing eleostearic acid and selenium monobromide.
Pharmaceutical compositions containing these reaction products and a pharmaceutically acceptable carrier are also encompassed by the invention
A process of preparing a selenium monobromide-oil reaction product is another embodiment of the invention. The process comprises reacting sufficient amounts of an eleostearic acid containing oil and selenium monobromide at a sufficient temperature and for a sufficient time to incorporate at least about 0.1 weight percent of selenium monobromide in the oil. The process generally involves reacting about 50 to 150 parts of oil with about 1 to 10 parts of powdered selenium monobromide at a temperature of 200 to 250° C. for a period of about 1 to 4 hours, until the reaction product becomes substantially clear, continuing heating the reaction product for about an additional 15 minutes to an hour, and decanting off the selenium monobromide which has not reacted.
A further embodiment is a method of treating a subject affected with a neoplastic condition, such as cancer. The method usually involves administering a therapeutically effective amount of a pharmaceutical composition containing a selenium monobromide-oil reaction product. The pharmaceutical composition is typically administered to the subject 2 to 4 times daily in capsule form, although a combination between oral and intradermal administration is also often used.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention relates to compositions of selenium monobromide-oil reaction product that exhibits a substantial antineoplastic activity. More specifically the invention encompasses compositions comprising a reaction product of selenium momobromide-in-oil prepared from oil containing eleostearic acid and selenium monobromide. The reaction product generally contains at least about 0.1 weight percent selenium monobromide and preferably between about 0.1 to 5 weight percent. Typically the reaction product exhibits ultraviolet absorption maxima associated with conjugated trienes and conjugated dienes.
Generally, any oil containing eleostearic acid can be used. Most preferably, however, the oils containing eleostearic acid in the form of 9, 11, 13-octadecatrienoic acid of formula CH
3
—(CH
2
)
3
—CH═CH—CH═CH—CH═CH—(CH
2
)
7
—COOH are preferred.
This acid is a fatty acid and is the chief component in “tung oil.” By warming selenium monobromide with oil containing eleostearic acid at a temperature of about 200 to 250° C., a selenium monobromide reaction product is formed.
Typically, the percentage of selenium monobromide in compositions prepared in this manner may vary within a broad range, but is preferably between about 0.1 to 5 weight percent for therapeutical use, compounds containing between about 2 to 4 weight percent by weight of selenium monobromide-oil reaction product are particularly useful.
The invention further relates to pharmaceutical compositions for administration to a human subject suffering from a neoplastic condition such as cancer. The pharmaceutical compositions typically include a reaction product of selenium momobromide-in-oil prepared from eleostearic acid and selenium monobromide, and a pharmaceutically acceptable carrier. Advantageously the pharmaceutical composition generally contains at least 0.1 weight percent. Preferably, however, the composition comprises about 0.1 to 5 weight percent of selenium monobromide-oil reaction product, more preferably about 2 to 4 weight percent and most preferably about 3 weight percent. The balance of the composition is usually composed of a pharmaceutically acceptable carrier. A liquid such as an oil, water or saline solution is typically used. If an oil is used as a carrier, vegetable, animal, fish oil, tung oil, sesame oil or combinations thereof can be used. Preferred oils are tung and sesame oils and combinations thereof.
The pharmaceutical composition usually further includes epichlorohydrin to enhance the antineoplastic properties of the reaction product. Epichlorohydrin is often included in an amount of between about 0.1 and 5 weight percent of the composition and more preferably between 0.5 and 1 weight percent. The epichlorohydrin used is preferably hydrolyzed.
Besides epichlorohydrin other epoxy agents can be used together or as an alternative to enhance the antineoplastic properties of the reaction product. Examples include epibromohydrine, 1,2-epoxy butane, 1,2-epoxy, 3 allyloxypropane, epoxyoctoxypropane, and 2,3-epoxypropylacrylate.
The pharmaceutical composition is usually sterilized by heating.
Generally the pharmaceutical composition is prepared as a single dosage form wherein the selenium monobromide-oil reaction product is present in an amount of from about 0.1 ml to 200 ml and more preferably about 05. to 5 ml per unit. Advantageously, a epichlorohydrin solution is present in an amount of from about 0.1 ml to 50 ml and more preferably about 1 to 5 ml per unit.
A further embodiment of the invention relates to a process of preparing a selenium monobromide-oil reaction product from eleostearic acid containing oil and selenium monobromide. The process typically comprises reacting sufficient amounts of an eleostearic acid containing oil and selenium monobromide at a sufficient temperature and for a sufficient time to incorporate at least about 0.1% of selenium monobromide in the oil.
A preferred embodiment of the inventive process consists of warming selenium monobromide with an oil, preferably a combination of sesame and “tung oil” up to a point when the mixture becomes clear, so that the elementary selenium monobromide substantially disappears. This process typically consists of reacting 50 to 150 parts, more preferably 75 to 125 parts and most preferably 97 parts oil containing eleostearic acid with 1 to 10 parts, more preferably 2 to 5 parts and most preferably 3 parts of powdered selenium monobromide at a temperature of about 200 to 250° C. for a period of about 1 to 4 hours and most preferably about 2 to 3 hours, until the reaction product becomes substantially clear. This is followed by continuing to heat the reaction product for about an additional 15 minutes to hour and most preferably for about a half hour, followed by decanting off the selenium monobromide that has not reacted.
During heating, the mixture is typically oxidized or heated in the presence of oxygen. The oxygen can be obtained by merely heating the formulation open to the atmosphere but preferably and advantageously, the source of oxygen is an oxygen-containing gas, such as air, injected into or bubbled through a heated oil, such as s
Krass Frederick
Winston & Strawn
LandOfFree
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