Zeaxanthin formulations for human ingestion

Abstract

Preparations are disclosed containing the 3R-3′R stereoisomer of zeaxanthin as a sole detectable isomer, packaged for oral ingestion by humans as a therapeutic drug or nutritional supplement. Zeaxanthin is a yellow carotenoid pigment found in the macula (in the center of the human retina), which helps protect retinal cells against phototoxic damage. The pure R-R stereoisomer can be prepared by fermenting cells, such as Flavobacterium multivorum (ATCC 55238), which do not create any detectable quantity of the undesired and potentially toxic S-S or S-R isomers, and which do not synthesize any other carotenoids. The R-R isomer can be concentrated, in large quantities and at low cost, into a viscous oily fluid containing about 5 to 20% zeaxanthin, by means of a simple solvent extraction process. This oily fluid can be mixed with a carrier such as vegetable oil and enclosed within a digestible capsule, comparable to a conventional capsule containing Vitamin E. Alternately, a zeaxanthin fluid can be added to various types of foods, such as margarine, dairy products, syrup, cookie dough, and certain types of meat preparations which are not subjected to harsh cooking. Additional purification steps can also be used to purify zeaxanthin to a granular or powdered state which contains nearly pure zeaxanthin. Such processing can be used to create formulations such as ingestible tablets, and particulate formulations that can be added to soups, salads, drinks, or other foods. Preferred stabilizers and anti-oxidants are also disclosed herein. When consumed by humans in any of these modes, the purified R-R stereoisomer of zeaxanthin can help treat and prevent macular degeneration, one of the leading causes of blindness and vision loss, especially among the elderly.

We claim:  
     
       1. A composition of matter comprising a digestible watertight capsule and a fluid contained therein, wherein the capsule and fluid are sized and designed for oral ingestion by a human and are pharmacologically acceptable, wherein the fluid contains a 3R-3′R stereoisomer of zeaxanthin, wherein the 3R-3′R stereoisomer of zeaxanthin constitutes at least about 90 percent of all zeaxanthin in the fluid while S-S and S-R stereoisomers constitute less than about 10 percent of all zeaxanthin in the fluid, and wherein the capsule contains at least about 3 milligrams of the 3R-3′R stereoisomer of zeaxanthin. 
     
     
       2. The composition of  claim 1  wherein the fluid contains no detectable quantity of S-S and R-S stereoisomers of zeaxanthin, and wherein the 3R-3′R stereoisomer of zeaxanthin is present as a sole detectable stereoisomer of zeaxanthin. 
     
     
       3. The composition of  claim 1  wherein the capsule contains at least about 10 milligrams of the 3R-3′R stereoisomer of zeaxanthin. 
     
     
       4. The composition of  claim 1  wherein the 3R-3′R stereoisomer of zeaxanthin constitutes at least about 90 percent by weight of total carotenoids in the fluid, and wherein other carotenoids which might compete against zeaxanthin for alimentary uptake or tissue deposition after ingestion constitute less than about 10 percent, by weight, of total carotenoids in the drug formulation. 
     
     
       5. The composition of  claim 1  wherein the 3R-3′R stereoisomer of zeaxanthin is synthesized by a method which comprises the step of culturing, under conditions which promote zeaxanthin biosynthesis, bacterial cells descended from a strain of Flavobacterium multivorum which has been given ATCC accession number 55238. 
     
     
       6. The composition of  claim 1  wherein the 3R-3′R stereoisomer of zeaxanthin is synthesized by culturing, under conditions which promote zeaxanthin biosynthesis, cells which have been genetically engineered to contain at least one zeaxanthin-synthesis gene containing a DNA sequence obtained from cells descended from a strain of Flavobacterium multivorum which has been given ATCC accession number 55238. 
     
     
       7. The composition of  claim 1  wherein the 3R-3′R stereoisomer of zeaxanthin is enclosed within micelles that were created using a bile salt. 
     
     
       8. A composition of matter comprising a tablet designed for oral ingestion by a human, wherein the tablet contains: 
       a. a 3R-3′R stereoisomer of zeaxanthin, and  
       b. a compressible binder material which is compatible with zeaxanthin and which causes a mixture of zeaxanthin and the binder material to retain its shape after compression under suitable pressure,  
       and wherein the tablet is pharmacologically acceptable and sized for oral ingestion by a human, and wherein the 3R-3′R stereoisomer of zeaxanthin constitutes at least about 90 percent of all zeaxanthin in the tablet while S-S and S-R stereoisomers constitute less than about 10 percent of all zeaxanthin in the tablet, and wherein the capsule  tablet contains at least about 3 milligrams of the 3R-3′R stereoisomer of zeaxanthin.  
     
     
       9. The composition of matter of  claim 8 , wherein the tablet is enclosed within a digestible coating layer that helps protect the zeaxanthin against oxidation. 
     
     
       10. A composition of matter comprising a formulation that is intended for oral ingestion by humans, wherein the formulation contains: 
       a. a nutritionally acceptable and tasteful food substance for human consumption as a carrier for zeaxanthin, and  
       b. a 3R-3′R stereoisomer of zeaxanthin which has been added to the food substance as a nutritional additive, in a quantity sufficient to provide a concentration of at least about 1% zeaxanthin by weight, wherein the 3R-3′R stereoisomer of zeaxanthin constitutes at least about 90 percent of all zeaxanthin in the food substance while S-S and S-R stereoisomers constitute less than about 10 percent of all zeaxanthin in the food substance.  
     
     
       11. The composition of matter of  claim 10  wherein the food substance is selected from the group consisting of margarine, dairy products, syrup, baked foodstuffs, cookie dough, brownie batter, meat preparations, and soup ingredients. 
     
     
       12. The composition of matter of  claim 10  wherein the zeaxanthin is microencapsulated and is enclosed within a protective coating that reduces degradation of the zeaxanthin by stomach acid. 
     
     
       13. The composition of matter of  claim 10  wherein the food substance comprises a granula formulation. 
     
     
       14. The composition of matter of  claim 13  wherein the granular formulation is selected from the group consisting of salt-containing flavoring mixtures, spice-containing flavoring mixtures, soup additives, baking mixes, and flavored additives for milk. 
     
     
       15. The composition of matter of  claim 13  wherein the zeaxanthin in the granular formulation is enclosed within a protective coating that reduces degradation of the zeaxanthin by stomach acid. 
     
     
       16. The composition of matter of  claim 10  wherein the foodstuff is selected from the group consisting of cheese, yogurt, milk, and beer. 
     
     
       17. A composition of matter comprising a digestible watertight capsule and a fluid contained therein, wherein the capsule and fluid are sized and designed for oral ingestion by a human and are pharmacologically acceptable, wherein the fluid contains a 3R-3′R stereoisomer of zeaxanthin, wherein the 3R-3′R stereoisomer of zeaxanthin constitutes at least about 90 percent of all zeaxanthin in the fluid while S-S and S-R stereoisomers constitute less than about 10 percent of all zeaxanthin in the fluid, and wherein at least a portion of the zeaxanthin in the capsule is created by a step comprising fermentation of cells which synthesize zeaxanthin. 
     
     
       18. A composition of matter comprising a tablet designed for oral ingestion by a human, wherein the tablet contains: 
       a. a 3R-3′R stereoisomer of zeaxanthin, and  
       b. a compressible binder material which is compatible with zeaxanthin and which causes a mixture of zeaxanthin and the binder material to retain its shape after compression under suitable pressure,  
       and wherein the tablet is pharmacologically acceptable and sized for oral ingestion by a human, and wherein the 3R-3′R stereoisomer of zeaxanthin constitutes at least about 90 percent of all zeaxanthin in the tablet while S-S and S-R stereoisomers constitute less than about 10 percent of all zeaxanthin in the tablet, and wherein at least a portion of the zeaxanthin in the capsule  tablet is created by a step comprising fermentation of cells which synthesize zeaxanthin.  
     
     
       19. A composition of matter comprising a digestible watertight capsule and a fluid contained therein, wherein the capsule and fluid are sized and designed for oral ingestion by a human and are pharmacologically acceptable, wherein the fluid contains a  3 R-   3 ′R stereoisomer of zeaxanthin, wherein the  3 R -   3 ′R stereoisomer of zeaxanthin constitutes at least about  90  percent of all zeaxanthin in the fluid while S - S and S - R stereoisomers constitute less than about  10  percent of all zeaxanthin in the fluid, and wherein the capsule contains a sufficient quantity of the  3 R -   3 ′R stereoisomer of zeaxanthin to treat or retard macular degeneration when used as a drug by patients suffering from macular degeneration.   
     
     
       20. The composition of matter of  claim 19 , wherein the capsule contains the  3 R-   3 ′R stereoisomer of zeaxanthin at a concentration of at least about  2  percent, by weight.   
     
     
       21. The composition of matter of  claim 19 , wherein the capsule contains at least about  3  milligrams of the  3 R-   3 ′R stereoisomer of zeaxanthin.   
     
     
       22. A composition of matter comprising a digestible watertight capsule and a fluid contained therein, wherein the capsule and fluid are sized and designed for oral ingestion by a human and are pharmacologically acceptable, wherein the fluid contains a  3 R-   3 ′R stereoisomer of zeaxanthin, where the  3 R -   3 ′R stereoisomer of zeaxanthin constitutes at least about  90  percent of all zeaxanthin in the fluid while S - S and S - R stereoisomers constitute less than about  10  percent of all zeaxanthin in the fluid, and wherein the capsule contains a sufficient quantity of the  3 R -   3 ′R stereoisomer of zeaxanthin to reduce long - term risk of macular degeneration in humans.   
     
     
       23. The composition of matter of  claim 19 , wherein the capsule contains a quantity of the  3 R-   3 ′R stereoisomer of zeaxanthin in a range of about  0 . 5  to  25  milligrams.   
     
     
       24. A nutritional supplement, comprising a  3 R-   3 ′R stereoisomer of zeaxanthin in a digestible capsule or tablet designed and sized for human ingestion, wherein the  3 R -   3 ′R stereoisomer of zeaxanthin constitutes at least about  90  percent of all zeaxanthin while S - S and S - R stereoisomers constitute less than about  10  percent of all zeaxanthin, and wherein the  3 R -   3 ′R stereoisomer of zeaxanthin constitutes at least about  90  percent of total carotenoids in the capsule or tablet, and wherein other carotenoids which might compete against zeaxanthin for alimentary uptake or tissue deposition after ingestion constitute less than about  10  percent, by weight, of total carotenoids in the capsule or tablet, and wherein the capsule or tablet contains a sufficient quantity of the  3 R -   3 ′R stereoisomer of zeaxanthin to reduce long - term risk of macular degeneration when such capsules or tablets are taken daily by humans.   
     
     
       25. A nutritional supplement, comprising a  3 R-   3 ′R stereoisomer of zeaxanthin in a digestible capsule or tablet designed and sized for human ingestion, wherein the  3 R -   3 ′R stereoisomer of zeaxanthin constitutes at least about  90  percent of all zeaxanthin while S - S and S - R stereoisomers constitute less than about  10  percent of all zeaxanthin, and wherein the  3 R -   3 ′R stereoisomer of zeaxanthin constitutes at least about  90  percent of total carotenoids in the capsule or tablet, and wherein other carotenoids which might compete against zeaxanthin for alimentary uptake or tissue deposition after ingestion constitute less than about  10  percent, by weight, of total carotenoids in the capsule or tablet, and wherein the capsule or tablet contains at least about  0 . 5  milligrams of the  3 R -   3 ′R stereoisomer of zeaxanthin.   
     
     
       26. A nutritional supplement, comprising a  3 R-   3 ′R stereoisomer of zeaxanthin in a digestible capsule or tablet designed and sized for human ingestion, wherein the capsule or tablet contains a  3 R -   3 ′R stereoisomer of zeaxanthin, wherein the  3 R -   3 ′R stereoisomer of zeaxanthin constitutes at least about  90  percent of all zeaxanthin in the capsule or tablet while S - S and S - R stereoisomers constitute less than about  10  percent of all zeaxanthin, and wherein the capsule or tablet contains a sufficient quantity of the  3 R -   3 ′R stereoisomer of zeaxanthin to cause deposition of detectable quantities of additional zeaxanthin in retinal tissue if one capsule or tablet is ingested daily.   
     
     
       27. The composition of matter of  claim 26 , wherein the  3 R-   3 ′R stereoisomer of zeaxanthin constitutes at least about  90  percent of all carotenoids in the capsule or tablet.   
     
     
       28. A nutritional supplement, comprising a  3 R-   3 ′R stereoisomer of zeaxanthin in a digestible capsule or tablet designed and sized for human ingestion, wherein the  3 R -   3 ′R stereoisomer of zeaxanthin constitutes at least about  90  percent of all zeaxanthin while S - S and S - R stereoisomers constitute less than about  10  percent of all zeaxanthin, and wherein the  3 R -   3 ′R stereoisomer of zeaxanthin constitutes at least about  90  percent of total carotenoids in the capsule or tablet, and wherein other carotenoids constitute less than about  10  percent, by weight, of total carotenoids in the capsule or tablet.   
     
     
       29. The nutritional supplement of  claim 28 , wherein the capsule or tablet contains at least about  0 . 5  milligrams of the  3 R-   3 ′R stereoisomer of zeaxanthin.   
     
     
       30. A nutritional supplement, comprising a  3 R-   3 ′R stereoisomer of zeaxanthin in a digestible capsule or tablet designed and sized for human ingestion, wherein the  3 R -   3 ′R stereoisomer of zeaxanthin constitutes at least about  90  percent of all zeaxanthin while S - S and S - R stereoisomers constitute less than about  10  percent of all zeaxanthin, and wherein the capsule or tablet contains at least about  0 . 5  milligrams of the  3 R -   3 ′R stereoisomer of zeaxanthin.   
     
     
       31. A nutritional supplement, comprising a  3 R-   3 ′R stereoisomer of zeaxanthin in a digestible capsule or tablet designed and sized for human ingestion, wherein the  3 R -   3 ′R stereoisomer of zeaxanthin constitutes at least about  90  percent of all zeaxanthin while S - S and S - R stereoisomers constitute less than about  10  percent of all zeaxanthin.   
     
     
       32. The nutritional supplement of  claim 31 , wherein the capsule or tablet contains at least about  0 . 5  milligrams of the  3 R-   3 ′R stereoisomer of zeaxanthin.   
     
     
       33. A nutritional supplement, comprising a  3 R-   3 ′R stereoisomer of zeaxanthin in a digestible capsule or tablet designed and sized for human ingestion, wherein the capsule or tablet contains a  3 R -   3 ′R stereoisomer of zeaxanthin, wherein the  3 R -   3 ′R stereoisomer of zeaxanthin constitutes at least about  90  percent of all zeaxanthin in the capsule or tablet while S - S and S - R stereoisomers constitute less than about  10  percent of all zeaxanthin, and wherein the capsule or tablet contains a sufficient quantity of the  3 R -   3 ′R stereoisomer of zeaxanthin to cause a detectable increase in zeaxanthin concentration in retinal tissue if one capsule or tablet is ingested daily.