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.

Description

BACKGROUND OF THE INVENTIONThis invention is in the field of pharmacology, and relates to human use of a yellow pigment called zeaxanthin (ZX) in preventing or treating macular degeneration, a disease which damages retinal tissue and causes blindness.This application is being simultaneously filed with a related patent application entitled, "Method of Making Pure 3R-3'R Stereoisomer of Zeaxanthin for Human Ingestion," Ser. No. 08 / 551,166. Both of these two patent applications are assigned to the same assignee (Applied Food Biotechnology, Inc. of O'Fallon, Mo.). The contents of that related application are incorporated herein by reference; upon issuance of a US patent based upon this current application, that related application will be opened for public inspection, if it has not already issued as a US patent.In addition to describing methods of manufacturing and purifying commercially useful quantities of isomerically pure R-R zeaxanthin, that related patent application contains a fa...

AI Technical Summary

Benefits of technology

This invention discloses zeaxanthin preparations which contain the 3R-3'R stereoisomer of zeaxanthin as a sole detectable isomer, packaged in a form that is intended and suitable 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 undesirable 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 pure 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.

Problems solved by technology

AMD affects millions of Americans over the age of 60, and is the leading cause of new blindness among the elderly.

These types of cellular debris may accumulate to abnormal levels for a number of reasons, including: (1) retinal cell damage caused by repeated exposure to too much light; (2) inherited genetic factors; (3) poor overall health of an individual; and (4) insufficient quantities of anti-oxidant compounds such as vitamins A, C, and E and selenium in a person's diet.

Accumulation of drusen occurs within the capillaries and in the Bruck's membrane, and can impede the transport of oxygen and nutrients to the retinal tissues, and the removal of metabolic wastes from the tissues.

Accumulation of one or both of these types of debris can disrupt the normal metabolic and cellular processes which must occur in order to maintain retinal and visual health.

Although the presence and the apparent or likely protective role of zeaxanthin in the retina have been recognized for more than a decade, no one has previously been able to create purified zeaxanthin preparations suitable for human consumption, either as drugs for treating macular degeneration, or as vitamin / nutritional supplements for reducing the risk of macular degeneration later in life.

This has been a major shortcoming, since there are no other effective means for treating or preventing macular degeneration; although .beta.-carotene, vitamin A, and vitamin E have generally beneficial anti-oxidant effects and may slightly retard the rate of macular degeneration, they do not rise to the level of truly effective treatments.

The primary (and previously insurmountable) problems that have been encountered in prior efforts to create purified forms of zeaxanthin for human ingestion include: (1) the extremely high level of chemical similarity between zeaxanthin and other less desirable carotenoids, including lutein and .beta.-carotene, make it extremely difficult to separate zeaxanthin from lutein and .beta.-carotene on any commercial scale; and, (2)zeaxanthin itself has three different stereoisomers, called the 3R-3'R isomer (which is desirable, and which is present in retinal cells), the 3S-3'S isomer (which is undesirable and which is not believed to exist naturally in retinal cells) and the S-R meso isomer.

Although hard scientific evidence of its roles and effects in the retina is not yet available, the S-R meso isomer of zeaxanthin is presumably less desirable than the naturally occurring R-R isomer.

It is effectively impossible to separate these three isomers of zeaxanthin from each other in commercial quantities; therefore, synthetic methods of creating racemic (mixed-isomer) mixtures of zeaxanthin are effectively useless in efforts to create zeaxanthin for human ingestion.

In addition, although it is theoretically possible to chemically synthesize enriched formulations having reduced quantities of the undesired S-S and S-R isomers, the necessary chemical techniques are extremely difficult and expensive, and have never been commercialized.

However, no one prior to this invention has ever been able to synthesize the purified R-R stereoisomer of zeaxanthin in any quantities sufficient for human consumption.

This failure can be attributed to the extraordinary difficulties of (1) separating zeaxanthin from other carotenoids, and (2) isolating the desired R-R isomer of zeaxanthin and removing the undesirable S-S and S-R isomers.

Clearly, zeaxanthin is not a widely available chemical, and is not available to the public except in extremely small trace quantities, in mixtures of other carotenoids.

Both of these patents are limited to using zeaxanthin in poultry or fish feed; although zeaxanthin is much more expensive than lutein, it is several times more effective (on a per-weight basis) than lutein in imparting color to animal flesh or chicken yolks.

However, non-fermentation processes suffer from several disadvantages.

They typically require numerous reaction steps, and each step has a less-than-100% yield, so that the final yield of zeaxanthin at the end of the multi-step processing tends to be relatively poor.

In addition, chemical synthesis tends to yield undesirable S-S and S-R stereoisomers of zeaxanthin, as well as various conversion products such as oxidized zeaxanthin, and zeaxanthin molecules which have lost one or more of the double bonds in the straight portion or end rings.

Accordingly, the entire process that would be required for both synthesis and purification using this technique would make production on a commercial scale very difficult, and extremely expensive.

However, the total carotenoid content of these feed additives is very low (only about 100 milligrams of total carotenoids per pound of poultry feed).

However, even though at least one commercially available carotenoid mixture that is sold in health food stores (the "Beta-Carotene Formula Preparation," sold by General Nutrition Corporation) lists zeaxanthin as one of the carotenoids contained in their carotenoid mixtures, none of the commercially available carotenoid mixtures contains more than extremely small, trace quantities of zeaxanthin.

Accordingly, as of late 1995, there are no available sources of concentrated or purified zeaxanthin for human use, either as a drug or as a nutritional supplement.

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