Title of Invention

"DIETARY SUPPLEMENT COMPOSITION FOR BLOOD LIPID HEALTH"

Abstract

ABSTRACT "Dietary Supplement Composition for Blood Lipid Health" A human or animal dietary supplement composition comprising one or more long chain (C24-C36) primary alcohols (policosanols) dispersed in food-grade oils or fats where the policosanol particle size is substantially less than ten (10) microns. The composition (Nanocosanol™) is effective and convenient for supporting blood lipid health. 23

Full Text

Related Application tOOOl] This application is based upon prior filed copending provisional application Serial No. 60/771,003 filed February 1, 2006, the entire subject matter of which is incorporated herein by reference in its entirety. Field of the Invention [0002] The present invention relates to dietary supplements, and, more particularly to the formulation of such supplements containing fatty alcohols. ['•' . ^ z ^ " ^ Background of the Invention [0003] Cholesterol effects have been studied for years. Examples of research are found in the following references, the disclosures which are hereby incorporated by reference in their entirety. [0004] . Albert, CM., K Oh, W Whang, JE Manson, CU Chae, MJ Stampfer, WC Willett and FB Hu. 2005. Dietary a-linolenic acid intake and risk of sudden cardiac death and coronary heart disaese. Cir-culation 112: 3232-3238. [00051 Castano, G, R Mas, M Arruzazabala et al. 1999. Effects of policcosanol and pravastatin on lipid profile, platelet aggregation and endothelemia in older hyperecholesterolemic patients. Jnt J Clin Phsrm Res. 4: 105. *• 2 'i * • w [0006] Gershkovich, P, A Hoffman. 2005. Uptake of l i p o p h i l i c d r u g s by plasma d e r i v e d i s o l a t ed c h y l o m i c r o n s : L i n t e r a l c o r e l a t i o n with' i n t e s t i n al l y m p h a t i c b i o a v a i l a b i l i t y . Eur J Pharm Sci. 26: 394- 404 . [0007] Law, MR, NJ Wald and SG Thompson. 1994. By houw much and how q u i c k l y d o e s r e d u c t i o n i n serum c h o l e s t e r o l c o n c e n t r a t i o n l o w e r r i s k of i s c h a e m i c h e a rt d i s e a s e ? BMJ" 3 0 8 : 367-372. [0008] Lusis, AJ. 2000. A t h e r o s c l e r o s i s . Nature. 4 0 7 ; 233-241. [0009] Mantzioris, E . , LG C l e l a n d , RA Gibson, MA Neumann, M Demasi and MJ J a m e s . 2000. Biochmical e f f e c t s of a d i e t c o n t a i n i n g foods e n r i c h e d with n-3 f a t t y a c i d s . Am J Clin Nutr 72: 4 2 - 4 8. [OOIO] Mas R. 2000. P o l i c o s a n o l . Drugs Future- 25: 5 6 9 - 5 8 6 . [0011] Oh, SY, J Ryeu, C H s i e h and DE B e l l . 1991. Eggs e n r i c h e d i n o-3 f a t t y a c i d s and a l t e r a t i o n s in l i p i d c o n c e n t r a t i o n s i n p l a s m a and l i p o p r o t e i n s and in b l o o d p r e s s u r e . Am J Clin Nutr. 54: 6 8 9 - 6 9 5. [0012] Rang, HP, MM D a l e and JM R i t t e r . 1999. Pharmacology. 4*^*' ed. C h u r c h i l l L i v i n g s t o n e , London. 8 3 0 . [0013] Simopoulos, AP. 1 9 9 9 . E s s e n t i a l f a t t y a c i ds i n h e a l t h and c h r o n i c d i s e s a s e . Am J Clin Nutr 7 0 ( s u p p l ) : 560S-9S. [0014] Taylor, JC, L R a p p o r t and GB Lockwood. 2003. O c t a c o s a n o l i n humeui h e a l t h . N u t r i t i o n . 19: 192-195. [0015] Zhao, G, TD E t h e r t o n , KR M a r t i n , SG West, PJ G i l l e s and PM K r i s - E t h e r t o n . 2004. D i e t a r y a - l i n o l e n ic a c i d reduces inflammatory a n d l i p i d c a r d i o v a s c u l a r r i s k . f a c t o r s in h y p e r c h o l e s t e r o l e m i c men and women. J Nutr 1 3 4 : 2991-2997. 3 - •i . . [0016] Cholesterol i s an essential component in the body and used in cell membranes. Excessive l e v e l s, however, can lead to hypercholesterolemia and a t h e r o s c l e r o s i s , which can result in coronary heart disease. Cholesterol i s transported v i a : high-, low-, intermediate-, and very low-density lipoproteins,- i chylomicron remants; and chylomicrons. High levels of J high-density lipoproteins are desirable because they i transport cholesterol from the peripheral tissues to the liver, thereby maintaining cholesterol homeostasis. The main transport mechanism, however, is low-density lipoprotein, which moves cholesterol in the blodd plasma and incorporates it into cell membranes. Increased levels of low-density lipoprotein, however, can interfere with uptake binding mechanisms. [0017J Statin drugs such as atorvastatin, fluvastatin, pravastatin and simvastatin are often administered to those suffering from cholesterol issues. These drugs inhibit competitively 3-hydjroxy-3- methylglutaryl coenzyme A reductase, thereby reducing cholesterol synthesis. Side effects of statins can ^ include myositis, headache, rash, angioederaa, gastrointestinal effects and altered liver functions. In addition, these drugs should not be used in patients with renal failure or in people with compromised liver function (Taylor et al. 2003). [0018] Dietary fatty acid intake can influence many health factors, but much interest has been placed on the n - 3 (omega-3) fatty acids. These essential fatty acids include a-linolenic (ALA), eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) . Various studies have shown that n - 3 fatty acids are essential for normal growth and development. They may also play a critical role in the prevention and treatment of coronary heart 4 - - m d i s e a s e , h y p e r t e n s i o n , d i a b e t e s and o t h e r inflammatory and autoimmune d i s o r d e r s (Siraopoulos 1999) . ALA is p r e s e n t i n c e r t a i n v e g e t a b l e o i l s ( f l a x s e e d , cranberrys e e d , c a n o l a and c h i a ) whereas EPA and DHA a r e found in f i s h , f i s h o i l and a l g a e p r o d u c t s. [0019] Between e t h n i c d i e t a r y g r o u p s i t has been shovm t h a t t h e h i g h e r r a t i o of n - 6 t o n - 3 in thrombocyte p h o s p h o l i p i d s can be a c a u s e for a h i g h er d e a t h r a t e from c a r d i o v a s c u l a r d i s e a s e . This i n c r e a s ed r a t i o a l s o r e s u l t s i n i n c r e a s e d r a t e s of type 2 d i a b e t e s , of which a t h e r o s c l e r o s i s i s a major c o m p l i c a t i o n (Weber, 1991) . Achieving t a r g e t l e v e l s of n - 3 f a t t y a c i d s can be d i f f i c u l t w i t h modem western. d i e t s d e f i c i e n t in ALA, EPA and DHA, and. e x c e s s i v e in t h e n - 6 l i n o l e i c a c i d . Target t i s s u e c o n c e n t r a t i o ns f o r ALA a n d EPA can be met with c o n s u m p t i o n of ALA ( M a n t z i o r i s et a l . 2000) . A p r i m a r y c a r d i o v a s c u l ar b e n e f i t from n - 3 f a t t y a c i d i n g e s t i o n can be r e d u c ed b l o o d c l o t t i n g in v e s s e l w a l l s and r e d u c e d v e n t r i c u l ar a r r h y t h m i a s , (Zhao e t a l . (2004)). Some s t u d i e s have found a d o s e - r e s p o n s e r e l a t i o n between n - 3 i n t a k e and b e n e f i c i a l e f f e c t s on c a r d i o v a s c u l a r d i s e a s e r i sk f a c t o r s . Some s t u d i e s have shown an i n v e r se r e l a t i o n s h i p between ALA i n t a k e and r i s k of sudden c a r d i a c d e a t h (Albert e t a l . (2005.)). [0020] Policosanols can be d e f i n e d a s a mibcture of l o n g c h a i n (C24-C36) a l i p h a t i c p r i m a r y a l c o h o l s , which a r e commonly d e r i v e d from sugar c a n e , r i c e bran, beeswax, wheat or sorghum. Predominant a l c o h o l s in t h i s group a r e t e t r a c o s a n o l , h e x a c o s a n o l , o c t a c o s a n ol and t r i a c o n t a n o l. [0021] Policosanols can lower c h o l e s t e r o l l e v e l s by i n h i b i t i n g c h o l e s t e r o l b i o s y n t h e s i s v i a d o w n r p g u l a t i on of 3 - h y d r o x y - 3 - m e t h y l g l u t a r y l Coenzyme A enzyme • 5 - expression (Menendez e t a l . 1994, McCarty 2002) . A study by Hernandez et a l . (1992) found a reduction in serum c h o l e s t e r o l l e v e l s of subjects talcing 20 mg policosanol per day for 4 weeks. S i g n i f i c a n t decreases in LDL l e v e l s , with i n c r e a s e d l e v e l s of HDL were also noticed. Another double-blind randomized study by . Castano, e t a l . (1999) i n v e s t i g a t e d the e f f e c t s of policosanol and p r a v a s t a t i n on the l i p i d p r o f i l e 'in older hypercholesterelemic patients. Policosanol was foxind t o increase HDL l e v e l s , but was a l s o more | e f f e c t i v e than pravastatin in lowering LDL l e v e l s and i the LDL:HDL r a t i o. [00221 Policosanols can a l s o protect l i p o p r o t e i ns from peroxidation, in b o t h l i p i d and p r o t e i n moieties . (Menendez e t a l . 1999) . This can be an important e f f e c t , s i n c e LDL o x i d a t i o n i s thought t o be a necessary s t e p in the development of a t h e r o s c l e r o s i s. [0023] Policocemols may provide fewer s i d e e f f e c ts them s t a t i n s , increase HDL cholesterol l e v e l s and have a reduced c o s t (Taylor e t a l . 2003) . [0024] One issue with policosanols are poor s o l u b i l i t y , and d i f f i c u l t y with absorbtion in the gut. Human s t u d i e s with fH] -octacosouiol showed the majority (81-91%) of total r a d i o a c t i v i t y was e x c r e d t e d in the feces, and only 1.2% of t o t a l r a d i o a c t i v i t y was found in urine (Mas, 2000) . [0025] Reducing the p a r t i c l e s i z e of poorly soluble compounds such as p o l i c o s a n o l to a micron or sub-micron range, improved autjsorbtion ahd b i o a v a i l a b i l t y is desiraJjle. Dl as WO 03/103632 uses a reduced p a r t i c l6 s i z e f o r . p o l i c o s a n ol that ±« l e s s than 2,000 nanometers, i . e . , 2 microns. The i n c r e a s e d surface area of the smaller nanoparticulate p a r t i c l e s requires the use of a surface s t a b i l i z e r . It i s p o s s i b l e to a l s o use pharmaceutically acceptable c a r r i e r with the 6 surface stabilizer. D2 as WO 02/052955 is directed to pharmaceutical and dietary compositions and functional food stuffs useful as coadjuvants for treating and preventing an aging process amd related conditions. It is directed to a lipidic mixture rich in polyunsaturated acids and vitamins, in.combination with at least two components selected from one or more terpenes selected from monoterpenes and/or sesquiterpenes, 1-piperoylpiperidine in the pure form and/or extracts or purified fractions enriched in black pepper containing it, one or more pollcosanols and/or policosanolic acids. There is no teaching concerning the policoseuiol in a micron or sub-micron range for improved absorption in bioavailability. Sxunmary of the Invention [0026] A human or animal dietary supplement composition comprises a blood lipid health-effective \ A 7 amount of one or more long chain (C24-C36) primaryalcohols (policosanols) dispersed in one or more foodgrade fats or oils, wherein the particle sizes of the alcohols are substantially less than 10 microns. [0027] The particle sizes of the alcohols can be substantially greater than 0.2 microns and substantially less than 5.0 microns. The alcohols can be selected from one of at least octacosanol, triacontanol and hexacosanol. The alcohols can also be | i derived from natural sources, including rice bran, beeswax, sugar cane, sorghum or wheat. [0028] In another aspect, the food-grade fats or oils contain one of at least: (a) not less than twenty five percent (25%) by weight of polyunsaturated fatty acids; (b) not less than ten percent (10%) by weight of omega-3 fatty acids; (c) not less than two and one-half percent (2.5%) by weight of squalene; and (d) not less than eight fifty parts per million (850 ppm) by weight of tocopherols and tocotrienols in total. [0029] The food-grade fats or oils could include at least one of cranberry seed oil, amaranth seed oil, fish and raarine/algal oils, safflower oil, sunflower seed oil, soybean oil, canola oil, olive oil, linseed oil, flax oil, hemp oil, borage oil, evening primrose oil, chia oil and hibiscus oil. [0030] In yet another aspect, the policosanols include about 0.1 percent by weight of the fats or oils to about 6.0 percent by weight of the fats or oils. The policosanols could also include about 0.5% by weight of the fats or oils to about 5.0%, by weight of the fats or oils, or from about 1.0% by weight of the 8 r fats or o i l s to about 5.0% by weight of the fats or o i l s . [0031] The composition could be formed from b i o l o g i c a l l y active e x t r a c t s and compounds, including vitamins, minerals, antioxidants, carotenoids, tocopherols, tocotrienols, phytosterols, polyphenols, } polysaccharides and bioflavonoids.. [0032] A vehicle for the composition could be an emulsion, solution, dispersion, cream, t a b l e t , capsules and powder. A vehicle for carirying the composition could be food, feed or beverage. [0033] A method aspect i s also set forth. Detailed Description of the Preferred Embodiments [0034] Different embodiments will now be described more f u l l y hereinafter with reference to the accompanying drawings, in which p r e f e r r e d embodiments are shown. Many d i f f e r e n t forms can be set forth and described embodiments should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so t h a t t h i s disclosure will be thorough and complete, and w i l l fully convey the scope t o those s k i l l e d in the a r t. [0035] The natural d i e t a r y supplement industry represents a $300 b i l l i o n dollar marJcetplace worldwide. Many natural botanical materials and e x t r a c t s have been used by mankind for h e a l t h purposes for thousands of years. In some parts of the world, n a t u r a l health products are preferred over chemical or pharmaceutical ones due t o reasons of r e l i g i o n , c u l t u r e, safety, cost and demonstrated efficacy. [0036] Among the b o t a n i c a l products that have a history of use in support of human blood l i p i d health are c e r t a i n f a t t y alcohols derived from botanical 9 waxes, for example, sugar cane wax, rice bran and other cereal waxes and bees wax. The most important of these are the long chain (C24-C36) primary alcohols, octacosanol, triacontanol and hexacosanol. [0037] Policosanols, as noted above, are known to have a number of beneficial effects on blood lipid health. These beneficial effects include lowering blood cholesterol levels, reducing Low Density Lipoproteins (LDL), increasing High Density Lipoproteins (HDL) and reducing blood triglycrerides. [0038] Some difficulties have been experienced in using policosanols to improve blood lipid health. For example, these fatty alcohols are poorly soluble in lipid carriers and completely insoliible in aqueous carriers. This greatly reduces their availability in the digestive tract. Normal digestion of fats and oils in the mammalian diet is achieved by emulsification with bile salts and phospholipids followed by direct adsorption of the resulting chylomicrons through the gut wall. Typical chylomicron sizes are 0.5 microns to 2 microns. [0039] Modem emulsification technology (nanotechnology) now makes it possible to produce dispersed particle sizes in liquid carriers into the 1 micron size. As noted above, many different physical emulsification techniques are available. [0040] In accordance with a non-limiting example of the present invention, one or more of these technologies is used to prepare a dietary supplement composition in which the policosanol particle sizes are substantially less than 10 micron range within an acceptable oil carrier (Nanocosanol'"') . The composition may include the use of food-grade emulsifiers, for example, polysorbates, lecithin, hydrolyzed lecithin, 10 mono- and di-glycerides, and acylated mono- and di-glycerides. The presence of the emulsifiers inhibits the tendency of the particles to adhere under electrostatic attractive forces. Such a composition has the advantage of increased digestability and stability on storage. [00411 In one aspect, the composition includes the selection of an oil carrier with beneficial blood lipid properties. Such fats and oils may include polyunsaturated fatty acids, omega-3 fatty acids, squalene, phytosterols, tocopherols and tocotrienols. Typical fats and oils, include, for example, fish oils, shark liver oil, cranberry seed oil, amaranth seed oil, sunflower seed oil, linseed oil, chia oil artd evening primrose seed oil. [0042] In another aspect, the composition.optimizes the balanced intake of both policosanols and the beneficial lipid carrier. By suitable selection of the ratio of the carrier oil to the policosanols, it is possible to produce the composition such that preferred intakes of both policosanols and the beneficial lipid can be conveniently administered in acceptable unit and daily doses. [00431 Such a composition as (Nanocosanol™) can be used to promote and support blood lipid health. Daily intake of such composition, in the preferred dose range, will provide the subject with the desired daily intakes of policosanols and lipid carrier, resulting in improved blood lipid profiles. This can include, for example, lower cholesterol, lower triglycerides, lower Low Density Lipoprotein (LDL) and higher High Density Lipoprotein (HDL). [0044] In accordance with one aspect of the present invention, a dietary supplement composition is 11 d i s c l o s e d (Nanocosanol™) i n which p o o r l y s o l u b le p o l i c o s a n o l s a r e d i s p e r s e d i n food-grade o i l s or f a t s, i n which t h e p o l i c o s a n o l p a r t i c l e s i z e s i n t he c o m p o s i t i o n a r e s u b s t a n t i a l l y l e s s than lO microns and p r e f e r a b l y in t h e range of from about 0,2 microns to a b o u t 5.0 m i c r o n s. [0045] In a c c o r d a n c e w i t h a n o t h e r a s p e c t of the p r e s e n t i n v e n t i o n , the b o d y ' s a b s o r p t i o n and u t i l i z a t i o n of t h e p o l i c o s a n o l s from t h e c o m p o s i t i o n is s u b s t a n t i a l l y enhanced as compared w i t h t h e a b s o r p t i on and u t i l i z a t i o n of p o l i c o s a n o l s a d m i n i s t e r e d i n s o l id o r t a b l e t form. The p o l i c o s a n o l d i s p e r s i o n of the c o m p o s i t i o n i s s t a b l e on s t o r a g e and d o e s n o t s e p a r a te from the l i p i d c a r r i e r. [004 6] The d i s c l o s e d l i p i d c a r r i e r u s e d i n the c o m p o s i t i o n may be s e l e c t e d from a group of o i l s and or f a t s t h a t a r e Icnown t o have b e n e f i c i a l e f f e c t s on b l o od l i p i d h e a l t h . .Such b e n e f i c i a l l i p i d s , f o r example, may c o n t a i n one o r more of p o l y u n s a t u r a t e d f a t t y a c i d s, p h y t o s t e r o l s , omega-3 f a t t y a c i d s , s q u a l e n e, t o c o p h e r o l s and t o c o t r i e n o l s. [0047] The c o n c e n t r a t i o n of p o l i c o s a n o l s of the c o m p o s i t i o n o p t i m i z e s t h e d a i l y i n t a k e of b o th p o l i c o s a n o l s and the b e n e f i c i a l l i p i d c a r r i e r . The p r e f e r r e d d a i l y i n t a k e of p o l i c o s a n o l s c a n be about 2 0 - 3 0 mg p e r day for an a d u l t . The p r e f e r r e d d a i ly i n t a k e for b e n e f i c i a l l i p i d s , however, i s o f t e n as h i gh a s from about 500 mg t o 5 , 0 0 0 mg per day f o r an a d u l t. The weight of p o l i c o s a n o l s i n t h e d i s c l o s e d c o m p o s i t i on i s from about 0 . 3 percent by weight of b e n e f i c i a l l i p id t o about 5.0 p e r c e n t by w e i g h t of b e n e f i c i a l l i p i d. Such a d i s c l o s e d c o a p o s i t i o n allows t h e r a t i o of b e n e f i c i a l l i p i d t o p o l i c o s a n o l s to r a n g e from about 3 3 3 : 1 t o about 2 0 : 1 . This r a t i o e n s u r e s t h a t a 12 p o l i c o s a n o l i n t a k e of about 25 mg p e r day i s always in combination w i t h from a b o u t 500 mg p e r day t o about 5,000 mg p e r day of t h e b e n e f i c i a l l i p i d . The d i s c l o s e d c o m p o s i t i o n a l l o w s d e l i v e r y of a p r e f e r r ed d a i l y dose of both p o l i c o s a n o l s and b e n e f i c i a l l i p i d in a s i n g l e f o r m u l a t i o n. [0048] It w i l l be un4|^aigtood by t h o s e i n t h e a rt t h a t l i q u i d d i e t a r y supplement d a i l y d o s e s of from about 500 mg t o about 5,000 mg can be c o n v e n i e n t ly d e l i v e r e d i n c a p s u l e s from about 500 mg t o about 1,000 mg. For example, a t h r e e p e r c e n t d i s p e r s i o n of p o l i c o s a n o l s in a b e n e f i c i a l l i p i d can c o n v e n i e n t ly supply 24 mg of p o l i c o s a n o l s per day t o g e t h e r w i t h 800 rag of b e n e f i c i a l l i p i d , when taken a s two 400 mg c a p s u l e s d a i l y. [0049] It w i l l be u n d e r s t o o d by t h o s e i n t h e a rt t h a t such a c o m p o s i t i o n , in c a p s u l e o r l i q u i d form, may be c o n v e n i e n t l y supplemented with o t h e r b i o l o g i c a l ly a c t i v e e x t r a c t s and compounds, i n c l u d i n g , for example, v i t a m i n s , m i n e r a l s , a n t i o x i d a n t s , c a r o t e n o i d s, t o c o p h e r o l s , t o c o t r i e n o l s , p h y t o s t e r o l s , f a t ty a l c o h o l s , p o l y s a c c h a r i d e s and b i o f l a v o n o i d s. [0050] The d i s c l o s e d d i e t a r y supplement c o m p o s i t i on (Nanocosanol^^) i s a n o v e l , improved, more e f f i c i e nt v e h i c l e f o r • t h e a d m i n i s t r a t i o n of p o l i c o s a n o l s in support of b l o o d l i p i d h e a l t h . I t i s e f f e c t i v e in lowering t h e blood serum c h o l e s t e r o l l e v e l of b o th normal and h y p e r c h o l e s t e r o l e m i c s u b j e c t s. 10051] The f o l l o w i n g examples a r e i l l u s t r a t i v e of t h e p r e s e n t i n v e n t i o n , and a r e not t o be c o n s t r u e d as l i m i t i n g t h e r e o f. 13 EXAMPLE 1 [0052] Supercritical CO2 Extracts of Cranberry (Vacclnium macrocarpon) Seed, Amaranth {AmaxanthuS' s hypochondriacus) Seed and Rice (Oryza sativa) bran wax were individually manufactured in a commercial 150 liter extraction unit. Within a heated vessel, the policosanol containing rice bran wax extract was dissolved into a mixture of cranberry and amaranth seed oily extracts at €5°C. After cooling to ambient temperature, soybean lecithin was combined. This resultant formulation was processed in a high pressure homogenization unit to obtain a stable dispersion of rice bran wax. The homogenizer is designed to produce high rates of shear and cavitation. Using light microscopy, average particle size was determined. Composition of the dispersion was as follows: Policosanols: 1.45%, average particle size 0.3 - 2.6 um. alpha-Linolenic acid: 13.2% Squalene: 3% Tocopherols: 499 pg/g Tocotrienols: 709 pg/g Phytosterols: 4.4 mg/g > EXAMPLE 2 [0053] The Nanocosanol f o r m u l a t i o n from Example 1 was e n c a p s u l a t e d i n s t a n d a r d g e l a t i n s o f t g e l s by a t h i r d p a r t y m a n u f a c t u r e r . Softgels were 690 mg nominal f i l l weight and e a c h c o n t a i n e d 10 mg p o l i c o s a n o l , 21 mg s q u a l e n e , 91 mg n - 3 f a t t y a c i d s ( a l p h a - l i n o l e n i c ) , 3.0 mg p h y t o s t e r o l s , 489 pg t o c o t r i e n o l s and 344 pg t o c o p h e r o l s , EXAMPLE 3 [0054] Nanocosanol^ s o f t g e l s , manufactured a c c o r d i n g . t o Example 2 were a d m i n i s t e r e d t o 11 s x i b j e c t s over an a p p r o x i m a t e l y 3-month p e r i o d . The s t u d y was a non- 14 placebo controlled open l a b e l t r i a l and used volunteers with normal and modestly elevated levels of serum cholesterol. Starting point individual cholesterol levels ranged from about 14 0 ho about 258. Dosage was 2 X 600 mg capsules per day providing 20 mg per day of policosanols together with 1200 mg per day of a 50:50 mixture of Cranberry and Amaranth Seed o i l s . In addition to the Policosonols, the Nanocosanol™ formulation provided tocopherols, t o c o t r i e n o l s , omega-6 and omega-3 f a t t y acids, polyunsaturated f a t t y acids and squalene. [0055] Subject blood samples were taken by an independent c l i n i c at 0 (Base), 30, 60 and 90 days. The blood samples were subjected to Blood Lipid by an authorized independent laboratory. [0056] Variables measured were Triglycerides, Cholesterol, LDL Cholesterol and HDL Cholesterol. [0057] All data were expressed as a difference (change) from the Base l e v e l for that subject and that variable. One subject did not complete a blood sample at 90 days so the total number of observations was 32 (11, 11, 10) . Analyses were based the combined data over a l l three periods. The mean changes for the Blood Lipid v a r i a b l e s were: Triglycerides - 4.72* p= 0.175 LDL Choi. - 10.06% p= 0.125 HDL Choi. + X.85% p« 0.175 OTHER Choi. - 5.23% p= 0.125 Choi. - 5.96% p= 0.050 LDL/HDL - 11.73% p= 0.050 Chol/HDL - 7.43% p= 0.05O [0058] The Cholesterol reduction of 5.96% was significant at the 5% l e v e l of p r o b a b i l i t y using the One-sided t - t e s t with 31 DF, as were the LDL/HDL r a t io and the Chol/HDL r a t i o . The other Blood Lipid decreases 15 are not s i g n i f i c a n t at the 5% Level but have only a 1 i n 6 to about 1 in 8 chance of occurring by chance. [0059] Analysis of Covariance was used t o estimate the linear regression of v a r i a b l e change on variable -Base level. Both the pooled within period regression coefficient and the overall regression c o e f f i c i e n t for most variables were negative, highly s i g n i f i c a n t at the 1% level (1 and 30 DF) and v i r t u a l l y i d e n t i c a l. [0060] Using the estimated regression equation, an estimate of the varieible reduction r e s u l t i n g from a "typical high-quartile" Base level was c a l c u l a t e d for each variable. These are shown as follows: T r i g l y c e r i d e b= - 0 . 2 9 1 8 p L.DL b= - 0 . 8 2 3 4 p HDL b= ^ 0 . 0 8 5 4 p-0.175 OTHER Choi b= - 0 . 2 8 7 0 p Choi b=. - 0 . 7 7 0 4 pi225 Chng= - 2 4 . 2 7 (-10.78%) LDL/HDL • b= - 0 . 4 5 3 4 p Chol/HDL b= - 0 . 3 5 7 7 p [0061] It can be seen from the r e s u l t i n g data that the Ncuaocosanol'"* treatment resulted in s i g n i f i c a n t and near significant reductions over base l e v e l -for a ll Blood Lipid variables except HDL which showed a small increase. Nanocosamol™ was c l e a r l y and demonstrably responsible for a significant improvement in Blood Lipid health. This is most c l e a r l y e s t a b l i s h e d for Total Cholesterol and the c r i t i c a l LDL/HDL and Chol/HDL r a t i o s . It i s also l i k e l y t h a t in a l a r g e r sample s i z e , the reductions in Triglycerides and LDL and the increase in HDL, both d e s i r a b l e treatment effects, would be confirmed as s i g n i f i c a n t. [0062] It i s also clear from the r e g r e s s i o n analysis t h a t decreases in Blood Lipid values are a function of the Base l e v e l . These r e s u l t s suggest t h a t for those subjects in the population with highly elevated serum 16 cholesterol values, Nanocosanol™ has the p o t e n t i a l to bring about 15% -20% reductions. [0063] Many modifications and other embodiments of the invention will come t o the mind of one s k i l l e d in the art having the benefit of the teachings presented in the foregoing d e s c r i p t i o n s and the associated drawings. Therefore, i t is understood that the invention i s not to be limited to the specific embodiments disclosed, and that modifications and embodiments are intended to be included within the scope of the appended claims. T 17 We claim: 1. A method of supporting the maintenance of healthy blood lipid levels, reducing blood serum cholesterol levels and treating hypercholesterolemy in human and animal subjects by the oral administration of a human or animal dietary supplement composition comprising a blood lipid health-effective amount of one or more long chain (C24-C36) primary alcohols comprising policosanols dispersed in food-grade fats or oils, wherein the average particle sizes of the alcohols are greater than 2.0 microns, wherein the food-grade fats and oils comprise: not less than twenty five (25%) by weight of polyunsaturated fatty acids; not less than ten percent (10%) by weight of omega-3 fatty acids; not less than eight fifty parts per million (850 ppm) by weight of tocopherols and tocotrienols in total; and wherein the policonsanols comprise from about 0.1 percent by weight of the fats or oils to about 6.0 percent by weight of the fats and oils, and further comprising a food-grade emulsifier. 2. The method as claimed in claim 1, wherein the composition is administered to the human or animal subjects in an amount to provide a daily intake of from about 0.125 mg of the policosanols per kilogram of body weight per day to about 0.750 mg of the policosanols per kilogram of body weight per day and preferably in the range of about 0.3 mg of policosanols per kilogram of body weight per day. 3. The method as claimed in claim 1, wherein the average particle sizes of the alcohols are greater than 2.0 microns and less than 10.0 microns. 4. The method as claimed in claim 1, wherein the alcohols comprise at least one of octacosanol, triacontanol and hexacosanoi. 5. The method as claimed in claim 1, and further comprising forming the alcohols from natural sources comprising at least one of rice bran, beeswax, sugar cane, sorghum and wheat. 18 6. The method as claimed in claim 1, wherein the food-grade fats or oils further comprise: not less than two and one-half percent (2.5%) by weight of squalene. 7. The method as claimed in claim 1, wherein the food-grade fats or oils comprise at least one of cranberry seed oil, amaranth seed oil, fish and marine/algal oils, safflower oil, sunflower seed oil, soybean oil, canola oil, olive oil, linseed oil, flax oil, hemp oil, borage oil, evening primrose oil, chia oil and hibiscus oil. 8. The method as claimed in claim 1, wherein the pollcosanols comprise from about 0.5% by weight of the fats or oils to about 5.0% by weight of the fats or oils. 9. The method as claimed in claim 1, wherein the pollcosanols comprise from about 1.0% by weight of the fats or oils to about 5.0% by weight of the fats or oils. 10. The method as claimed in claim 1, further comprising adding biologically active extracts and compounds selected from at least one of minerals, carotenoids, tocopherols, tocotrienols, phytosterols, polyphenols, polysaccharides and bioflavonoids. 11. The method as claimed in claim 1, further comprising forming a delivery vehicle as an emulsion, solution, dispersion, cream, tablet, capsules or powder. 12. The method as claimed in claim 1, further comprising forming a delivery vehicle as a food, feed or beverage. 13. A human or animal dietary supplement composition comprising a blood lipid healtheffective amount of one or more long chain (C24-C36) primary alcohols comprising pollcosanols, dispersed in food-grade fats or oils, wherein the average particle sizes of the alcohols are greater than 2.0 microns, wherein the food-grade fats or oils comprise: (a) not less than twenty five percent (25%) by weight of polyunsaturated fatty acids; (b) not less than ten percent (10%) by weight of omega-3 fatty acids; 19 (c) not less than eight fifty parts per million (850 ppm) by weight of tocopherols and tocotrlenols in total; and wherein the policosanols comprise from about 0.1 percent by weight of the fats or oils to about 6.0 percent by weight of the fats or oils, and further comprising a food-grade emulsifier. 14. The composition as claimed in claim 13, wherein the average particle sizes of the alcohols are greater than 2.0 microns and less than 10.0 microns. 15. The composition as claimed in claim 13, wherein the alcohols are selected from at least one of octacosanol, triacontanol and hexacosanol. 16. The composition as claimed in claim 13, wherein the alcohols are selected from natural sources comprising at least one of rice bran, beeswax, sugar cane, sorghum and wheat. 17. The composition as claimed in claim 13, wherein the food-grade fats or oils comprise at least one of cranberry seed oil, amaranth seed oil, fish and marine/algal oils, safflower oil, sunflower seed oil, soybean oil, canola oil, olive oil, linseed oil, flax oil, hemp oil, borage oil, evening primrose oil, chia oil and hibiscus oil. 18. The composition as claimed in claim 13, wherein the policosanols comprise from about 0.5% by weight of the fats or oils to about 5.0% by weight of the fats or oils. 19. The composition as claimed in claim 13, wherein the policosanols comprise from about 1.0% by weight of the fats or oils to about 5.0% by weight of the fats or oils. 20. The composition as claimed in claim 13, and further comprising biologically active extracts and compounds, including at least one of carotenoids, phytosterols, polyphenols, polysaccharides and bioflavonoids. 21. The composition as claimed in claim 13, and further comprising a delivery vehicle as an emulsion, solution, dispersion, cream, tablet, capsules or powder. 20 22. The composition as claimed in claim 13, and further comprising a delivery vehicle for carrying the composition comprising food, feed or beverage. 23. The composition as claimed in claim 13, wherein the food-grade fats or oils contain squalene. 24. The composition as claimed in claim 13, wherein the average particle sizes of the alcohols are less than 10 microns. 25. A method for enhancing gastrointestinal motility in humans and other mammals, comprising administering a therapeutically effective amount of a composition having one or more long chain (C24-C36) primary alcohols as policosanols dispersed in one or more food-grade fats or oils, wherein the food-grade fats or oils comprise: (a) not less than twenty five percent (25%) by weight of polyunsaturated fatty acids; (b) not less than ten percent (10%) by weight of omega-3 fatty acids; (c) not less than eight fifty parts per million (850 ppm) by weight of tocopherols and tocotrienols in total; and wherein the policosanols comprise from about 0.1% by weight of the fats or oils to about 6.0% by weight of the fats or oils, and the particle sizes of the alcohols are greater than 2.0 microns. 26. The method as claimed in claim 25, wherein the food-grade fats or oils further comprises not less than two and one-half percent (2.5%) by weight of squalene. 27. The method as claimed in claim 25, wherein the alcohols are selected from natural sources including rice bran, beeswax, sugar cane, sorghum and wheat. 28. The method as claimed in claim 25, wherein the food-grade fats or oils include at least one of cranberry seed oil, amaranth seed oil, fish and marine/algal oils, safflower oil, 21 sunflower seed oil, soybean oil, canola oil, olive oil, linseed oil, flax oil, hemp oil, borage oil, evening primrose oil, cha oil and hibiscus oil. 29. The method as claimed in claim 25, wherein the policosanols comprise from about 0.5% by weight of the fats or oils to about 5.0% by weight of the fats or oils. 30. The method as claimed in claim 25, wherein the policosanols comprise from about 1.0% by weight of the fats or oils to about 5.0% by weight of the fats or oils. 31. The method as claimed in claim 25, the composition further comprising biologically active extracts and compounds, including vitamins, minerals, antioxidants, carotenoids, tocopherols, tocotrienols, phytosterols, polyphenols, polysaccharides and bioflavonoids. 32. The method as claimed in claim 25, the composition further comprising a delivery vehicle as an emulsion, solution, dispersion, cream, tablet, capsules and powder. 33. The method as claimed in claim 25, the composition further comprising a deliver vehicle for carrying the composition comprising food, feed or beverage. Dated this 31** day of July, 2008 ^ ' (N^ti Wilson) Of Anand and Anand Advocates ^ Attorney for the Applicant I ! I 22

Documents:

17013-P2_Refiling.pdf

6669-delnp-2008-abstract.pdf

6669-DELNP-2008-Assignment (07-11-2008).pdf

6669-delnp-2008-Assignment-(09-07-2012).pdf

6669-delnp-2008-Claims-(10-01-2014).pdf

6669-delnp-2008-Claims-(14-12-2011).pdf

6669-delnp-2008-claims.pdf

6669-delnp-2008-Correspondence Others-(09-07-2012).pdf

6669-delnp-2008-Correspondence Others-(10-01-2014).pdf

6669-DELNP-2008-Correspondence Others-(10-09-2012).pdf

6669-delnp-2008-Correspondence Others-(11-05-2012).pdf

6669-delnp-2008-Correspondence Others-(26-12-2013).pdf

6669-DELNP-2008-Correspondence-others (07-11-2008).pdf

6669-DELNP-2008-Correspondence-others (18-12-2008).pdf

6669-delnp-2008-Correspondence-Others-(02-09-2013).pdf

6669-delnp-2008-Correspondence-Others-(04-02-2013).pdf

6669-delnp-2008-Correspondence-Others-(13-08-2013).pdf

6669-delnp-2008-Correspondence-Others-(14-12-2011).pdf

6669-delnp-2008-correspondence-others.pdf

6669-delnp-2008-description (complete).pdf

6669-delnp-2008-form-1.pdf

6669-delnp-2008-Form-13-(14-12-2011).pdf

6669-delnp-2008-form-18.pdf

6669-delnp-2008-form-2.pdf

6669-DELNP-2008-Form-3 (18-12-2008).pdf

6669-delnp-2008-Form-3-(04-02-2013).pdf

6669-delnp-2008-form-3.pdf

6669-delnp-2008-form-5.pdf

6669-DELNP-2008-GPA (07-11-2008).pdf

6669-delnp-2008-pct-210.pdf

6669-delnp-2008-pct-220.pdf

6669-delnp-2008-pct-237.pdf

6669-delnp-2008-pct-401.pdf

6669-delnp-2008-pct-409.pdf

6669-delnp-2008-pct-416.pdf

ABSTRACT.pdf

Form 2 complete specifications.pdf

REVISED CLAIMS.pdf