CA1303498C

CA1303498C - Composition and method for treatment of copper deficiency

Info

Publication number: CA1303498C
Application number: CA000540782A
Authority: CA
Inventors: Emanuel Revici
Original assignee: Individual
Current assignee: Individual
Priority date: 1985-10-01
Filing date: 1987-06-29
Publication date: 1992-06-16
Anticipated expiration: 2009-06-16
Also published as: WO1989000040A1

Abstract

COMPOSITION AND METHOD
FOR TREATMENT OF COPPER DEFICIENCY

ABSTRACT

A method for making a composition containing a fatty acid or fatty ester compound and copper. The compositions produced by the method. Administration of these compositions to a patient to increase the copper content of cells or tissue having a copper deficiency or to treat at least some of the symptoms of diseases or adverse effects caused by this copper deficiency.

Description

COMPOSITION AND ME HOD
FOR TREATMENT OF COPPER DEFICIENCY

Technical Field The present disclosure concerns a method to treat various conditions resulting from copper deficiency and preparations for same.

Back~round It is known that the abnor~al cells in ~eneral and the neoplastic cells in particular are poor in copper, a fact which is considered as including and enhancing their abnormal character. It is also known that the blood plasma o~ subjects 15 with such abnormal condltions is especially rich in copper, ; apparently due to the body's attempt t~ correct the cellular copper deficiency. The form under which the copper is circulating in the blood, that is, mainly as ceruloplasmin, however, is not the proper form from which the copper can be 20 taken by the abnormal cells.

Summarv of the Invention The invention comprises novel compositions of fatty 25 acids, ester, or oils which include copper incorporated therein. These composition are mads by heating the oil component to a temperature of at least above 230~C for a sufficient time to incorporate a predetermined amount of copper into the oil. At least about 0.1% can be used, a~though 30 between l and 10% is preferred.
These compositions of the invention may ~e administered to a patient who has cells or tissue which are deficient in copper to increase the copper content as well as ~o treat the symptoms of diseases or adverse effects caused by the copper deficient cells or tissue.
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Detailed Descriptîon of the Invention I have found that in general, the abnormal cells and tissues in the body have free lipids. Thus, a lipid or compound having a lipidic character introduced into the body can be selectively taken by the abnormal cells. Accordingly, it is believed that a copper compound having lipidic properties is useful as a therapeutic agent for patients who have such abnormal cells~
I have found that copper can be incorporated in the 10 molecule of a fatty acid by heating together an organic or inorganic salt of copper with a fatty acid or its oil.
Preferably, the fatty acid or oil i5 previously oxidized by being heated and mixed with air or oxygen3 The mixtures of copper and fatty acids or oil are heated at a temperature above 15 about 230C for a time until an exothermic reaction is observed, which reaction indicates that the incorporation is taking place.
Examples of ~he copper/fatty acid or oil compositions that can be used according to the invention include the 20 reaction products of allylic unsaturated fatty acids or esters and a copper salt. These reaction products are produced by heating a liquid composition containing a fatty acid or fatty ester, structurally characterized by allylic unsaturation with a copper salt. Applicant believes that any copper salt is 25 suitable for thi~i invention. Preferably, the copper salt is an organic copper salt such as cupric acetate, and the liquid is preferably oxidized for example, by bubbling air or oxygen through the reaction mixture.
The allylically unsaturated compound is preferably a 30 naturally occurring oil containing polyunsturated fatty esters, such as an animal, vegetable, or ish oil, and, particularly, polyunsaturated vegetable oils. Sesame oil, a vegetable oil consisting largely of triglycerides, is the most advantageous composition found to date in the practice of this invention.

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The composition utilized should contain a significant percentage of molecular species having allylic moieties to render the compositions useful according to the invention~
Such moieties are indicated by the following partial structures -CH-CH-CH2-CH=CH- and/or -CH CH-CH=CH-CE~2- As indicated, the unsaturation can be conjugated or nonconjugated, but the composition must contain allylic methylene hydrogen.
Such compGsitions may initially be oxidized or heated in the presence of air or oxygen at the temperature range between about 100C and about 150C. The oxygen can be 10 obtained by merely heating the composition in a vessel which is open to the atmosphere, but preferably and advantageously, the source of oxygen i5 a gas such as air which i5 injected into the heated oil. Introduction of air also provides a source of agitation.
The heating step ls conducted for a period of from about 15 minutes to about two hours. The temperature should be maintained at an upper limit within the range of about 230~C to 250~C, and preferably about 235UC to 240C. These temperature limitations are based on a heating time of about one half hour.
20 The temperatures can be altered within limits depending on the time of heating For example, when the temperature is about 235C, the time is about one-half hour, while temperatures as high as 250C require a shorter period of time for heating.
Higher temperatures for a prolonged period of time tend to 25 degrade the composition and should thus be avoided.
Agitation, by stirring for example, aids in the reaction, and experiments to date indicate that a fairly violen~ stirring is advantageous. The introduction of air into ~he mix~ure during the heating is also very advantageous, 30 particularly when the mixture is not subjected to prolonged heating and thus, is the preferred me~hod. The mixing or stirring can be accomplished with the introduction of the air.
After the reaction has taken place, the mixture is cooled. The remaining fluid is ready for use after appropriate , .
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sterilization for injection or incorporated into capsules, such as gelatin, for oral administration.
The precise nature of the compositions which result from the above-described treatment or the identity of the effective component or components is no~ presently known. It is known, however, that these compositions do include copper and that a proportion of copper in the range of about 1 to 10 weight percent has been found to be effective.
As mentioned above, although any copper salt may be used, an organic salt of copper, such as cupric acetate, is 0preferred, wi~h the copper bonding the eleostearic acid present in this oil. Although any amount above 0.1% of copper incorporated into the composition i~ useful, the preferred amount ranges between about 1 to 10 weight percent.
The products obtained have the copper incorporated in 5general at the level o~ the double bonds of the different unsaturated fatty acids, this causes their toxicity to be exceptionally low. The injection of 1 ml of a product having 5% copper to a mouse does not kill it.
The incorporated copper composition may be 20administered orally, by injections, sublingually or rectally in ~he appropriate formulation.
The incorporated copper is believed to be absorbed by the abnormal cells, thus compensating for their low copper content. This treatment produces objective and subjective 25improvement in the conditions, of patient~ having a variety of diseases based upon such abnormal cells. The neoplastic diseases are examples of diseased in which low cellular copper abnormal cells are found.
Such low cellular copper abnormal cells are believed 30to cause an anabolic imbalance in the body~ This anabolic imbalance can be analyzed and dia~nosed by blood and urine analyses. An eosinophilia (above 100/cmm), a low red cell sedimentation rate (below 15 ml/l hour), a low serum potassium (below 4~5 mEq), a urinary alkaline pH (above 7), low specific 3~ravity (below 1.016), high surace tension (above 89 . ~
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dynes/cm), and high calcium or chloride excretio~ are indications of an anabolic imbalance. (The opposite analyses would indicate a catabolic imbalance.~
These analyses and clinical manifestations have to be changed by the administration of the incorporated copper compound. In a 5% copper incorporated preparation, amounts from about 2 to lO ml daily are predilectly used for the treatment of this anabolic imbalanceO For the neoplastic conditions with catabolic imbalances, low doses from l/lO to 2 ml daily are predilectly used. In general the higher the dose used, the better are the clinical results.
Interesting results are those concerning pain, the changes induced in the lesions manifesting first an ation upon pain. Manifest changes in the tumors and in the subjective manifestations of the neoplastic diseases are ohtained even in a very short time. Thus~ the incorporated copper appears as a predilect treatment of the symptoms of neoplastic conditions, and possibly to the treatment of such condition themselves.
Good results were also obtained in the use of the incorporated copper compounds for the different manifes~ations 20 of AIDS ~acquired immune deficiency syndrome) as well as for the ARC (AIDS related complex).
Interesting also are the resul~s in almost all the different conditions, such as neurological conditions, epilepsy and others, the problem of cellular copper deficiency being a 25 general pathological occurrence. Interesting is the action of the lipidic copper products on the viral infections.
The incorporated copper composition may be administered together with different other agents.
While it is apparen~ that the invention herein 30 disclosed is well calculated to ful~ill the objects above stated, it will be appreciated that numerous modifications and embodiments may be devised by those skilled in the art, and it is intended that ~he appended claims cover all such modifications and embodiments as fall within the true spirit 35 and scope of the present invention.

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Claims

The embodiments of the invention in which an exclusive property or privilege is claimed defined are as follows:

1. A method for making a composition which comprises heating at least one fatty acid or fatty ester compound having an allylic unsaturation of the type -CH=CH-CH2-CH=CH- or -CH=CH-CH=CH-CH2- with a copper salt at a temperature above about 230°C for a sufficient period of time to incorporate at least about 0.1% by weight copper into the composition.

2. The method of claim 1 wherein the fatty acid or fatty ester compound is oxidized by mixing the compound with air heating the mixture.

3. The method of claim 1 wherein the fatty acid or fatty ester compound is heated at a temperature range of about 230 to 250°C for a time of about one-half hour so as to incorporate at least 1% by weight copper into the composition.

4. A method for making a composition which comprises heating a vegetable oil with an organic copper salt at a temperature of above about 230°C for a sufficient period of time to incorporate about 1% by weight copper into the composition.

5. A method for making a composition which comprises heating sesame seed oil, air, and cupric acetate at a temperature from about 230 to 250°C for about one-half hour with agitation to incorporate at least about 1% by weight copper into the composition.

6. The composition produced by the method of claim 1, 2 or 3.

7. The composition produced by the method of claim 4.

8. The composition produced by the method of claim 5.

9. A pharmaceutical composition for use in increasing the copper content of cells or tissue having a copper deficiency which comprises an effective amount of the composition of claim 6.

10. A pharmaceutical composition for use in increasing the copper content of cells or tissue having a copper deficiency which comprises an effective amount of the composition of claim 7.

11. A pharmaceutical composition for use in increasing the copper content of cells or tissue having a copper deficiency which comprises an effective amount of the composition of claim 8.

12. A pharmaceutical composition for use in treating at least some of the symptoms of disease or an adverse effect in a patient caused by cells having a copper deficiency which comprises an effective amount of the composition of claim 6.

13. A pharmaceutical composition for use in treating at least some of the symptoms of disease or an adverse effect in a patient caused by cells having a copper deficiency which comprises an effective amount of the composition of claim 7.

14. A pharmaceutical composition for use in treating at least some of the symptoms of disease or an adverse effect in a patient caused by cells having a copper deficiency which comprises an effective amount of the composition of claim 8.

15. A method of preparing a copper and oil reaction product for pharmaceutical use which comprises heating a mixture of an animal, vegetable or fish oil having an allylic unsaturation of the type -CH=CH-CH2-CH=CH- or -CH=CH-CH=CH-CH2- and an organic copper salt at a temperature of between about 230°C and 250°C for between about 15 minutes and 2 hours to incorporate by exothermic reaction between about 0.1 and 10% by weight copper into the oil.

16. The method of claim 15 where the oil is oxidized before the copper compound is added by mixing the oil with air and heating the mixture.

17. The method of claim 15 wherein the mixture is oxidized by introducing air into the mixture while heating at the state temperature and time ranges.

18. The copper and oil reaction product produced by the method of claim 15, 16 or 17.

19. A pharmaceutical composition for use in increasing the copper content of cells or tissue having a copper deficiency which comprises a therapeutically effective amount of the composition of claim 18.

20. A method of preparing a copper and oil reaction product for pharmaceutical use which comprises oxidizing an unsaturated vegetable oil by heating a mixture of air and the oil, and mixing said oxidized vegetable oil with an organic copper salt at a temperature of between about 230°C and 250°C for about one-half hour to incorporate by exothermic reaction between about 1 and 10% by weight copper into the oil.

21. The copper and oil reaction product produced by the method of claim 20.

22. A pharmaceutical composition for use in increasing the copper content of cells or tissue having a copper deficiency which comprises a therapeutically effective amount of the composition of claim 21.

23. A method of preparing a copper and oil reaction product for pharmaceutical use which comprises heating sesame seed oil, air and cupric acetate at a temperature of between about 235°C and 240°C for about one-half hour with agitation to incorporate by exothermic reaction about 1% by weight copper into the oil.

24. The copper and oil reaction product produced by the method of claim 23.

25. A pharmaceutical composition for use in increasing the copper content of cells or tissue having a copper deficiency which comprises a therapeutically effective amount of the composition of claim 24.