Internet for Pharmaceutical and Biotech Communities
| Newsletter | Advertising |
 
 
 

  

Pharm/Biotech
Resources

Outsourcing Guide

Cont. Education

Software/Reports

Training Courses

Web Seminars

Jobs

Buyer's Guide

Home Page

Pharm Patents /
Licensing

Pharm News

Federal Register

Pharm Stocks

FDA Links

FDA Warning Letters

FDA Doc/cGMP

Pharm/Biotech Events

Consultants

Advertiser Info

Newsletter Subscription

Web Links

Suggestions

Site Map
 

 
   



 

Title:  Composition and method for treating age-related disorders
United States Patent: 
7,033,612
Issued: 
April 25, 2006

Inventors:
 Kang; David S. (16 Forest Gate Cir., Oakbrook, IL 60523); Kang; Chunghee Kimberly (16 Forest Gate Cir., Oakbrook, IL 60523)
Appl. No.:
 336150
Filed:
 January 3, 2003


 

Pharm/Biotech Jobs


Abstract

There is provided a composition for the prevention and treatment of age-related physical and mental disorders that includes phospholipids that have been extracted from chick embryos aged between about 6 days old and about 14 days old. Also provided is a method for extracting these phospholipids by incubating them for between about 6 days to about 14 days. The chick embryos are then prepared for chemical extraction, and the lipids are extracted from the chick embryos. Further provided is a method for preventing and treating age-related physical and mental disorders, in human subjects in need thereof, by administering a sufficient dosage of a composition including phospholipids extracted from chick embryos incubated for between about 6 days and about 14 days to a human subject.

BRIEF SUMMARY OF THE INVENTION

According to one aspect of the present invention, there is provided a composition for the prevention and treatment of age-related physical and mental disorders. This composition includes phospholipids that have been extracted from chick embryos aged between about 6 days old and about 14 days old.

According to another aspect of the present invention, there is provided a method for extracting phospholipids from chick embryos for use in a composition for alleviating age-related physical and mental disorders. The fertilized eggs are incubated for between about 6 days to about 14 days. The chick embryos are separated and the lipids of chick embryos are extracted by organic solvents. Phospholipids are separated from solvents and residual water by evaporation and freeze-drying.

According to yet another aspect of the present invention, there is provided a method for using a composition for preventing and treating age-related physical and mental disorders, in a human subject in need thereof. A dosage of a composition including phospholipids extracted from chick embryos incubated for between about 6 days and about 14 days is administered to the subject. The dosage is of a sufficient amount to increase physical endurance.

According to still another aspect of the present invention there is provided a method for treating age-related physical and mental disorders, in a human subject in need thereof. A dosage of the composition including phospholipids extracted from chick embryos incubated for between about 6 days and about 14 days is administered to the patient. The dosage is of a sufficient amount to increase physical endurance.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates generally to the field of therapeutic uses of embryonic phospholipids, particularly plasmalogens of phosphoglycerides prepared from chicken embryo tissues, for prevention and treatment of age-related disorders. The present invention provides a composition for preventing and treating these age-related physical and cognitive disorders that comprises a phospholipid extract collected from 6 to 14 day-old chick embryos. The present invention comprises pharmaceutical compositions containing early chick embryo phospholipids, particularly those including plasmalogens, mixed into an inert, nontoxic carrier for oral or sublingual administration, and methods of preparing and administering these compositions.

There are generally two groups of phospholipids present in embryonic and post-natal chicken brains. The first group comprises phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol. The second group comprises plasmalogens of choline, ethanolamine and serine. This second group also includes sphingomyelin, and ethanolamine ether phosphatides. In young chicken embryos, the phospholipids of the first group dominate the chemical makeup of the embryos. Up until chick embryos are about 16 days old, the phospholipids of the first group are synthesized very rapidly, while there is only a slight increase in the amount of phospholipids of the second group. When chick embryos are aged between about 16 and about 20 days old, the phospholipids of the second group begin to rapidly synthesize as well, bringing the level of phospholipids of the second group close to that of the first group. For the purposes of preventing and treating age-related illnesses, the preferred embryo age is between about 6 and about 14 days old; more preferably, the embryo age is between about 9 and about 10 days old.

Phospholipids in early to mid-stage embryos—those aged from about 6 to about 14 days—contain strikingly different phosphoglycerides than late-stage embryos. These mid-stage phosphogeycerides contain alkenyl and acyl groups not typically present in late stage phosphoglycerides. For example, mid-stage phosphoglycerides comprise ethanolamine plasmalogens with short chain lauric or myristic ester linkages and palmityl ether linkages.

Plasmalogens and phospholipids extracted from mid-stage embryos play an important role in the prevention and treatment of age-related disorders. For example, the presence of plasmalogens in substantial amounts in the inner layer of biological membranes is well-documented, indicating that these lipids are involved in signal transduction following binding regulatory mechanisms within these membranes. It is believed that there is specific participation by ether lipids in the chemiosmotic process, similar to the participation of such inner mitochondrial membrane components as coenzyme Q, NADH, FMN and cytochrome a 3. It is also believed that membrane lipid composition is strongly influenced by lipid shape, and that the observed changes in lipid composition serve to stabilize the bilayer arrangement of cellular and subcellular membranes. All these factors can strengthen the membranes of the cell's surface, as well as those of subcellular organelles, reducing the effects of age-related illnesses.

Plasmalogens also are potential protectors against the oxidation of LDL proteins. About 3% to about 5% of total LDL phospholipids are plasmalogens. In vitro oxidation of LDL using an oxidizing agent induces a selective reduction of plasmalogen subgroups in phosphatidylcholine and phosphatidylethanolamine. VLDL and LDL plasmalogens were oxidized to a greater extent (99% decrease) compared to HDL plasmalogens (35%), suggesting that plasmalogens play a protecting role with respect to atherogenesis, the build-up of fats and fatty acids in the blood stream. This also contributes to the regulation the blood pressure, which is also affected by age.

The content of cholesterol and phospholipids in 8 and 16 day old chick embryo fibroblasts has also been compared. Cholesterol content did not change, whereas total phospholipids decreased with time change, resulting in an increase of the cholesterol to phospholipid ratio. Further, the fatty acid composition of phosphatidylcholine and phosphatidylethanolamine in these fibroblasts showed unique features. For example, the content of myristic acid was depleted by more than two-thirds from the 8 to 16 day old fibroblast. This indicates a change in the fluidity of membranes during development, a change that aids in keeping cells relatively strong and helps to assuage age-related conditions.

To prepare a composition for preventing and treating age-related conditions, chick embryos are selected that are aged between about 6 days and about 14 days; preferably, between about 9 days and about 10 days. These embryos have been preferably incubated for the duration of aging at a temperature between about 90° F. to about 100° F., preferably between about 95° F. to about 100° F., more preferably between about 99° F. to about 100° F. The embryos are then stored until use by immediately freezing the embryos and storing them in a freezer at a temperature between about -70° C. to about -90° C., preferably between about -75° C. to about -85° C., more preferably between about -80° C. to about -85° C.

To prepare the frozen embryos for use, they are first thawed, and then briefly minced with a blender. The minced embryo pieces are then centrifuged by any method known to one of skill in the art. The centrifugation is performed in order to separate out the liquid portions of the embryos. Any residual water in the solid phase is then removed by further centrifugation methods after mixing with ethanol. The residual water may also be removed by freeze-drying methods, warm air currents, or any other dessication method known to one of skill in the art. If centrifugation methods are used with ethanol, acetone may be added to the ethanol to improve drying properties. In a large scale preparation, minced embryo tissues may be dried in an evaporator having a partial vacuum. In such an evaporator, the vacuum pressure should be maintained such that the boiling point of the minced tissues is between about 50° C. and about 60° C. Preferably, the vacuum pressure is maintained such that the boiling point is between about 54° C. and about 57° C. If necessary, a warm air current is used to further dry the condensed minced embryo mixtures. The air current should be maintained at about 180° C. to about 200° C., preferably at about 188° C. to about 192° C., for best results in drying the embryo pieces without chemically destroying the biological compounds.

The minced, dried embryo tissues are then mixed with suitable organic solvents, such as a hexane-ethanol solution, wherein the lipids in the minced embryo tissues are extracted into the organic solvent. Preferably, the lipids are extracted under stirring. As a result, a lipid extract is removed from the liquid phase, and the lipid extract is temporarily set aside. The liquid phase left after lipid extraction is then concentrated to about 5% to about 15% of the original volume, preferably concentrated to about 9% to about 11% of the original volume. This may be done by any method known in the art, but is preferably performed by using a flash evaporator at less than about 40° C. to about 50° C., more preferably at about 43° C. to about 46° C.

The liquid phase is then separated into an aqueous and organic layer. The organic layer is then further concentrated to create a phospholipid extract. In order to eliminate any residual water and organic solvents from the phospholipid extract, the extracted phospholipids can be lyophilized after mixing them with a portion of inactive ingredients. For example, an alimentary antioxidizing agent and isoleucine can be added to the lyophilized mixture. The phospholipid extract is preferably lyophilized by a standard freeze-drying method, but may be purified by any method known to those of skill in the art.

A small portion of the phospholipid extract is set aside and saved for quality analysis of the resulting lipids in the composition. Analysis can be performed by thin layer chromatography, high performance liquid chromatography (HPLC), gas chromatography, NMR spectrometry, or any combination of these techniques. Typically, NMR spectroscopy shows that as a result of this method, the phospholipid extract contains phosphatidylcholine comprising about 50% to about 70% of the total phospholipids, more preferably comprising about 55% to about 66% of the total phospholipids. Plasmalogens of phosphatidylcholine are generally not detected in any appreciable amount in the phospholipid extract resulting from this method. Phosphatidylethanolamine and its plasmalogen comprises about 20% to about 30% of the total phospholipids in the phospholipid extract, more preferably 23% to about 26% of the total phospholipids. Further analysis also shows that the major fatty acids found in the phospholipid extract include C18:0 and C16:0 (from phosphatidylethanolamine) and C16:0, C20:4n6, C16:1, C22:6n3, and C18:1 (from phosphatidylcholine). The chemical nomenclature used above indicates the length of the fatty acid (indicated by the number directly after the "C"), as well as the number of double bonds along its backbone (indicated by the number directly after the colon) and the position of these double bonds (indicated by the number after an "n").

To eliminate any residual water and organic solvent, the phospholipid extracts are lyophilized after mixing them with an alimentary antioxidizing agent and amino acids. Amino acids are a basic building block of the human body, and supplements including these amino acids serve to help replenish those levels. Any amino acid that is hydrophobic may be used in this compound. Common amino acids, such as lysine, leucine, isoleucine and cyteine may be used. More preferably, isoleucine is used. A particularly hydrophobic amino acid, isoleucine is often found concentrated in muscle tissues. In particular, isoleucine aids the formation of hemoglobin in the human body. Isoleucine also serves to stabilize and regulate blood sugar and energy levels throughout the body.

Further, the phospholipid extract can be lyophilized or otherwise admixed with an antioxidant. Antioxidant compounds are those that reduce the oxidization of the cellular structure. This slows the cellular aging process, and keeps cells stronger. In the present mixture, the addition of antioxidants serves to help prevent the oxidation of phospholipids. Preferred antioxidants for use in the composition comprise vitamin E, as well as its derivatives, and vitamin C, as well as its derivatives. More preferably, vitamin E and ascorbyl palmitate, a vitamin C derivative, are used. Vitamin E, a fat-soluble, naturally occurring vitamin, has particularly good anti-oxidant properties. Vitamin E has been linked to a reduction in the rate of coronary diseases. Vitamin C serves not only to prevent cellular oxidation, but also to aid the synthesis of collagen in the body, which itself helps to repair aged skin and muscle tissues. Ascorbyl palmitate has been shown to be a particularly effective derivative of vitamin C in supplements. These antioxidants may also replace the amino acids in an embodiment of the present invention.

Additionally, a binding element is preferably added to the phospholipid extract. The binding element serves to hold the ingredients of the composition together. Any stearate-based compound safe for human consumption may be used, such as calcium stearate and zinc stearate. However, a preferred binding element is magnesium stearate. A derivative of magnesium, this chemical compound is often used as a food additive to promote binding in food products.

Polysaccharides, which are carbohydrate-based starches comprising a plurality of sugar molecules, also help to hold the ingredients of the composition together. Any polysaccharide may be used; however, preferred polysaccharides in the composition include lactose, cellulose, and fructose. More preferably, lactose and cellulose are used.

Other ingredients may also be added to improve the taste or consistency of the final formulation, as is known in the art. For example, a flavoring agent may be added to the composition. Such a flavoring agent would improve the taste of the composition upon administration, letting it taste more like mint, fruit, or any taste preferred by the consumer. Use of a flavoring agent is preferable in a composition to be administered in a liquid form, but may also be used in a solid form composition.

After preparing the phospholipid extract, the chosen ingredients are then mixed together to create doses of the final composition. This composition may be in a liquid form or a solid capsule form. The composition may be administered in any form known to those in the art; for example, a solid capsule may be a film-coated tablet or a soft gelatin tablet. As a further example, a liquid composition may be administered as a liquid elixir or as a sublingual or oral spray. While the form of administration may change, the dosage should be calculated such that a single dosage comprises about 40 mg to about 100 mg of phospholipid extract. More preferably, a single dosage comprises about 50 mg to about 80 mg of phospholipid extract.
 


Claim 1 of 31 Claims

1. A composition for alleviating age-related physical and mental disorders, comprising phospholipids extracted from chick embryos aged between about 6 days old and about 14 days old, wherein said phospholipids comprise about 50% to about 70% by weight of phosphatidylcholine and about 20% to about 30% by weight of phosphatidylethanolamine and its plasmalogens.

____________________________________________
If you want to learn more about this patent, please go directly to the U.S. Patent and Trademark Office Web site to access the full patent.

 

 

     
[ Outsourcing Guide ] [ Cont. Education ] [ Software/Reports ] [ Training Courses ]
[ Web Seminars ] [ Jobs ] [ Consultants ] [ Buyer's Guide ] [ Advertiser Info ]

[ Home ] [ Pharm Patents / Licensing ] [ Pharm News ] [ Federal Register ]
[ Pharm Stocks ] [ FDA Links ] [ FDA Warning Letters ] [ FDA Doc/cGMP ]
[ Pharm/Biotech Events ] [ Newsletter Subscription ] [ Web Links ] [ Suggestions ]
[ Site Map ]