Abstract:
A method of lowering blood cholesterol in a non-diabetic patient by at least 30% is described. The method involves orally administering for 30 consecutive days a fenugreek seed extract composition. Various methods of preparation and various formulations are described. Physiologically effective pharmaceutical compositions and beverages containing fenugreek seed extracts and other active components are also disclosed.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS  
       [0001]     This application claims benefit under 35 U.S.C. § 119(e) of U.S. provisional patent application No. 60/535,731, filed Jan. 10, 2004, the disclosure of which is herein incorporated by reference. 
     
    
     BACKGROUND OF THE INVENTION  
       [0002]     The present invention is directed to relatively stable, convenient and patient-friendly compositions of fenugreek seed extract, including pharmaceutically acceptable compositions thereof. The invention further provides a method for preparing such compositions. The compositions of this invention are advantageously used in methods for treating a non-diabetic individual having a disorder associated with high cholesterol. Specifically, the present invention includes employing fenugreek seed extract, or compositions or formulations comprising them, to lower cholesterol in a non-diabetic to a greater degree compared to conventional preparations. Fenugreek seed extracts, or compositions or formulations comprising them, have several advantages, including: the capability of daily oral dosing, ease of use in suspension form, safety, efficacy, purity, relative stability, and resuspendability over a short period of time.  
         [0003]     The invention relates to an extraction process that uses fenugreek, fenugreek extracts or grinds (herein referred to as “juice” or “extract”). The instant compositions also encompass carbonated or non-carbonated beverages and formulations containing the aforementioned fenugreek extract which may further contain minerals, vitamins, nutrients, standard excipients, carriers, physiologically active agents, etc. The formulation may be in a ready-to-drink form in a container, a concentrate, or as a powder mix to be reconstituted with water or other ingestible liquids. Moreover, it may be compounded in the form of a pill, capsule, granules, microparticles, nanoparticles or liposomes.  
         [0004]     The instant inventors have discovered that treating non-diabetic patients suffering from high cholesterol levels with the above-mentioned composition(s) significantly lowers the patient&#39;s cholesterol levels. While it may be anticipated that any soluble fiber may achieve a decrease in the blood cholesterol level (U.S. Pat. Nos. 4,834,990, 5,009,819, 5,558,897 and 5,851,578, incorporated herein by reference), the instant process yields the following unexpected result. While the prior art generally discloses a reduction of several points using “juices” such as those of fenugreek often in the range of 5-15 points (which is in the general range of 2-10%), the inventors compositions(s) derived via the specific extraction process yields invariably reductions in the range of 30% or higher (Table 1). For instance, consuming little amounts of fenugreek “juice” over thirty days of consecutive usage provides dramatic results enumerated herein. This data is unprecedented in the literature. In fact, such a result is neither disclosed in the prior art nor would it be obvious to one of ordinary skill in the art.  
         [0005]     As stated above, the present invention also provides a ready-to-drink beverage or a concentrate in a solid (e.g., powder mix) or a liquid form for reconstitution into a beverage. Furthermore, such beverages may be supplemented with soluble minerals (e.g., calcium), vitamins, soluble fibers, flavors, colors, adjuvants, taste-masking agents, conventional solvents and carriers.  
         [0006]     Commercially marketed fiber-containing products are not often well received by patients with respect to taste and appearance of the final product at the time of consumption. The present invention alleviates these problems.  
         [0007]     The present invention also has the advantage of simplicity of extraction. The present inventors have discovered that simply boiling fenugreek seeds in water results in an extraction (the “juice” or “extract”) that can be directly employed in the claimed compositions to lower cholesterol to the specified degree.  
         [0008]     Furthermore, the instant inventors have also noted the following benefits of using fenugreek “juice” (without any observed side effects): 
    1) alleviation of a woman&#39;s birth pains;     2) aiding women suffering from a lack of estrogen;     3) regulating menstrual period;     4) assisting in milk production in nursing women;     5) treating rheumatism;     6) treating cough and sore throat pain; and    
 
         [0015]     7) acting as a sexual stimulant in women.  
                                                                                             TABLE 1                                       Cholesterol       Cholesterol       Cholesterol                           levels       levels       levels                   Cholesterol   following       following three       following                   levels prior   one month       months of       one year of                   to fenugreek   of fenugreek       fenugreek       fenugreek                   treatment   treatment   %   treatment   %   treatment   %       Case #   Age   Sex   (mg/100 ml)   (mg/100 ml)   Decrease   (mg/100 ml)   Decrease   (mg/100 ml)   Decrease                                1   33   M   320   280   12.5   240   25   190   40.6       2   41   M   280   220   21.4   180   35.7   150   46.4       3   48   M   330   280   15   240   27   180   45.5       4   57   M   285   255   10.5   215   24.6   205   28.1       5   52   M   337   245   27.3   200   40.7   165   51       6   44   M   295   265   10.2   215   27.1   198   33       7   48   M   305   285   7   255   16.4   204   33.1       8   39   M   440   380   13.6   285   35.2   205   53.4       9   65   M   276   245   11.2   205   25.7   155   43.8       10   58   M   288   238   17.4   220   23.6   210   27.1       11   48   M   305   245   19.7   185   39.3   175   42.6       12   47   M   265   245   7.5   235   11.3   215   18.9       13   55   M   276   266   3.6   260   5.8   235   14.9       14   62   M   457   352   23   320   30   265   42       15   27   M   305   265   13.1   255   16.4   210   31.1       16   55   M   330   290   12.1   260   21.1   199   39.7       17   25   M   345   245   29   235   32   225   35       18   36   M   294   230   22   210   29   189   36       19   47   M   282   252   11   222   21.3   185   34.4       20   32   M   288   232   19.4   210   27.1   155   46.2       21   53   M   270   235   13   215   20.4   195   28       22   60   M   284   235   17.3   185   35   175   38.4       23   61   M   295   245   17   215   27.1   200   32.2       24   33   M   340   240   29.4   200   41.2   192   44       25   22   M   290   210   27.6   190   34.5   182   37.2       26   42   M   287   255   11.1   220   23.3   185   35.5       27   60   M   290   265   8.6   240   17.2   185   36.2       28   58   M   280   270   3.6   230   17.9   220   21.4       29   40   M   275   245   10.9   220   20   185   32.7       30   32   M   455   380   16.5   290   36.3   220   51.6       31   45   M   295   220   25.4   190   35.6   170   42.4       32   43   M   270   245   9.3   210   22.2   200   26       33   24   M   290   265   8.6   210   27.6   195   32.8       34   47   M   290   245   15.5   205   29.3   175   39.7       35   45   M   297   265   10.8   220   26   200   32.7       36   51   M   330   285   13.6   245   25.8   199   40       37   47   M   280   210   25   200   28.6   185   40       38   78   M   295   235   20.3   215   27.1   193   34.6       39   41   M   260   210   19.2   200   23.1   185   29       40   29   M   299   236   21.1   205   31.5   198   33.8       41   16   M   335   285   19.8   220   38   195   45.1       42   46   M   298   256   14.1   225   24.5   205   31.2       43   24   M   270   225   16.7   205   24   200   26       44   45   M   260   215   17.3   195   25   180   30.8       45   41   M   250   210   16   200   20   190   24       46   55   M   270   245   9.3   215   20.4   195   27.8       47   28   M   280   250   10.7   210   25   200   28.6       48   22   M   310   290   6.5   245   20.9   198   36.1       49   35   M   295   290   0   310   0   295   0       50   48   M   345   355   0   340   0   348   0       51   55   M   295   298   0   290   0   310   0       52   45   M   280   280   0   275   0   285   0       53   38   F   390   320   18   260   33.3   230   41       54   41   F   355   280   21.1   220   38   185   47.9       55   42   F   450   350   22.2   320   28.9   230   48.9       56   47   F   290   270   6.9   220   24.1   175   39.7       57   55   F   425   375   11.8   325   23.5   240   43.5       58   45   F   335   285   14.9   265   20.9   185   44.8       59   43   F   296   221   25.3   185   37.5   155   47.6       60   35   F   270   245   9.2   205   24.1   145   46.3       61   32   F   265   205   22.7   165   37.7   110   58.5       62   31   F   260   195   25   175   32.7   135   48.1       63   37   F   245   195   20.4   155   36.7   125   49       64   35   F   280   240   14.3   192   31.4   180   35.7       65   49   F   285   220   22.8   210   26.3   205   28.1       66   56   F   295   215   27.1   205   30.5   185   37.3       67   41   F   268   210   21.6   196   26.9   145   45.9       68   46   F   295   255   13.6   195   33.9   190   35.6       69   59   F   278   244   12.2   215   22.7   202   27.3       70   55   F   245   185   24.5   155   36.7   135   44.9       71   50   F   560   495   11.6   432   22.9   298   46.8       72   66   F   332   285   14.2   234   29.5   200   39.8       73   44   F   260   220   15.4   195   25   165   36.5       74   59   F   290   240   17.2   195   32.8   165   43.1       75   37   F   305   205   32.8   175   42.6   155   49.2       76   69   F   295   265   10.2   210   28.8   200   32.2       77   55   F   275   255   7.3   215   21.8   195   29.1       78   24   F   290   230   20.7   198   31.7   170   41.4       79   47   F   310   265   14.5   245   21   200   35.5       80   48   F   270   210   22.2   190   29.6   180   33.3       81   38   F   310   255   17.7   220   29   185   40.3       82   57   F   277   210   24.2   185   33.2   155   44       82   33   F   288   245   14.9   198   31.3   185   35.8       84   68   F   280   200   28.6   192   31.4   165   41.1       85   44   F   285   255   10.5   210   26.3   195   31.6       86   37   F   275   225   18.2   205   25.5   173   37.1       87   82   F   310   255   17.7   225   27.4   196   36.8       88   75   F   286   255   10.8   210   26.6   200   30.1       89   53   F   265   210   20.8   195   26.4   190   28.3       90   42   F   280   255   8.9   220   21.4   200   28.6       91   47   F   291   240   17.5   210   27.8   195   33       92   77   F   295   265   10.2   225   23.7   195   33.9       93   44   F   288   265   8   235   18.4   215   25.3       94   48   F   350   285   18.6   235   32.9   200   42.9       95   52   F   285   235   17.5   200   29.8   175   38.6       96   39   F   275   245   10.9   215   21.8   200   27.3       97   57   F   265   210   20.8   200   24.5   180   30.1       98   28   F   285   285   0   275   0   290   0       99   62   F   315   310   0   320   0   305   0                  
 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0016]     Unless otherwise defined herein, scientific and technical terms used in connection with the present invention shall have the meanings that are commonly understood by those of ordinary skill in the art. Furthermore, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. Generally, nomenclatures used in connection with, and standard techniques described herein are those well known and commonly used in the art.  
         [0017]     For millennia, fenugreek ( Trigonella foenum graecum ) has been used both as a medicine and as a food spice in India and the Middle East. Fenugreek seeds have been used for centuries by practitioners of Indian Ayurvedic medicine as well as traditional Chinese Medicine. The fenugreek plant is native to the Mediterranean areas of Europe and to India. Fenugreek is generally regarded as safe and non-toxic. In India its leaves are cooked as a vegetable and also used as animal feed. Fresh seeds are often used as flavoring or sprouted and eaten as a salad green. Fenugreek seeds have a slight maple taste and are often used in production of imitation maple flavorings. The fenugreek plant produces small white flowers in late summer and after the flowers die, large pods that contain 10-20 irregularly-shaped yellow seeds develop. In some parts of the world, dried fenugreek seeds are ground for a curry spice. However, they may also be boiled to produce a yellow dye, roasted as a coffee substitute, or used to flavor foods and tobacco. After the seeds are collected from the plants, the plants may be chopped and used as fertilizer.  
         [0018]     Recent interest in fenugreek focuses on its potential benefits to lower blood sugar in diabetics. In some individuals dietary intake of soluble fiber can slow absorption and subsequent digestion of food that results in a slower rise in blood sugar levels. Some clinical studies have demonstrated that fenugreek seeds reduce blood glucose levels and decrease insulin resistance in mild type-2 diabetic patients. Fenugreek contains the amino acid, 4-hydroxyisoleucine, which appears to increase the body&#39;s production of insulin when blood sugar levels are elevated.  
         [0019]     Studies have also shown that fenugreek may lower levels of triglycerides and serum cholesterol levels in diabetics. In terms of weight control, the soluble fiber in fenugreek seeds can reduce dietary fat absorption by binding to fatty acids as well as create a sensation of “fullness,” thereby reducing appetite. Finally, because fenugreek seeds contain estrogen-like saponins, blood levels of total cholesterol, LDL and triglycerides can be reduced (with no change in HDL). Although it is by no means the only major risk factor, elevated serum cholesterol is associated with a greater risk of heart disease. Cholesterol levels under 200 mg/dl are considered optimal. However a low cholesterol level is not any guarantee of good heart health, since some people with low cholesterol levels do suffer heart attacks. Evaluation of changes in cholesterol requires consultation with a healthcare professional and should include measurement of total serum cholesterol, as well as HDL and LDL cholesterol. The present inventors observed no side effects or poisoning as a result of consuming the fenugreek “juice,” even in large quantities. In fact, it was observed that doping or consuming mega-dose has no effect versus dosing in light quantity. The inventors found that amounts as little as two ounces per day for 30 days provided the therapeutic effect. Other patients consumed as much as about five cups a day to derive the identical beneficial effect.  
         [0020]     Fenugreek seed extracts may also have other medical uses. It may reduce the amounts of calcium oxalate in the kidneys, often a contributing factor in kidney stones. In animal studies, fenugreek also appeared to lessen the chance of developing colon cancer by blocking the action of certain enzymes. Topically, the gelatinous texture of fenugreek seed may have some benefit for soothing skin that is irritated by eczema or other conditions. It has also been applied as a warm poultice to relieve muscle aches and gout pain. To be applied topically, fenugreek seeds can be ground into a powder, and then soaked in hot water to form a thick gel. Fenugreek is a mild but effective laxative.  
         [0021]     The instant fenugreek extract or “juice” can be combined with any pharmaceutically acceptable excipient. According to this invention, a “pharmaceutically acceptable excipient” is an excipient that acts as filler or a combination of fillers used in pharmaceutical compositions. Preferred excipients included in this category are: 1) amino acids, such as glycine, arginine, aspartic acid, glutamic acid, lysine, asparagine, glutamine, proline; 2) carbohydrates, e.g., monosaccharides such as glucose, fructose, galactose, mannose, arabinose, xylose, ribose; 3) disaccharides, such as lactose, trehalose, maltose, sucrose; 4) polysaccharides, such as maltodextrins, dextrans, starch, glycogen; 5) alditols, such as mannitol, xylitol, lactitol, sorbitol; 6) glucuronic acid, galacturonic acid; 7) cyclodextrins, such as methyl cyclodextrin, hydroxypropyl-β-cyclodextrin and alike; 8) inorganic molecules, such as sodium chloride, potassium chloride, magnesium chloride, phosphates of sodium and potassium, boric acid, ammonium carbonate and ammonium phosphate; 9) organic molecules, such as acetates, citrate, ascorbate, lactate; 10) emulsifying or solubilizing/stabilizing agents like acacia, diethanolamine, glyceryl monostearate, lecithin, monoethanolamine, oleic acid, oleyl alcohol, poloxamer, polysorbates, sodium lauryl sulfate, stearic acid, sorbitan monolaurate, sorbitan monostearate, and other sorbitan derivatives, polyoxyl derivatives, wax, polyoxyethylene derivatives, sorbitan derivatives; and 11) viscosity increasing reagents like, agar, alginic acid and its salts, guar gum, pectin, polyvinyl alcohol, polyethylene oxide, cellulose and its derivatives propylene carbonate, polyethylene glycol, hexylene glycol, tyloxapol. Salts of such compounds may also be used. A further preferred group of excipients includes sucrose, trehalose, lactose, sorbitol, lactitol, mannitol, inositol, salts of sodium and potassium, such as acetate, phosphates, citrates and borate, glycine, arginine, polyethylene oxide, polyvinyl alcohol, polyethylene glycol, hexylene glycol, methoxy polyethylene glycol, gelatin, hydroxypropyl-β-cyclodextrin, polylysine and polyarginine.  
         [0022]     The fenugreek extract or “juice” according to this invention can also be combined with a carrier or excipient, a substance that, when added to a therapeutic, speeds or improves its action. Examples of carriers or excipients include, for example, buffer substances, such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, waters, salts or electrolytes, such as Protamine sulfate, disodium hydrogen phosphate, sodium chloride, zinc slats, colloidal silica, magnesium, trisilicate, cellulose-based substances and polyethylene glycol.  
         [0023]     This invention advantageously permits consumption of the instant fenugreek extract or “juice” by a human. In one embodiment, the compositions according to this invention are administered about once a day. In another embodiment, the compositions according to this invention are administered about once a day for a month. In yet another embodiment, the compositions according to this invention are administered for a period longer than a month. It will be appreciated by those of skill in the art that the specific treatment regimen will depend upon factors such as the cholesterol level in the patient, the age and weight of the patient to be treated, general physical condition of the patient and the judgment of the treating physician.  
         [0024]     In order that this invention may be better understood, the following examples are set forth. These examples are for the purpose of illustration only and are not to be construed as limiting the scope of the invention in any manner. Numerous other variations of the present invention will be appreciated by those skilled in the art, in view of the disclosure herein. The exact compositions, methods of preparation and embodiments shown are not limiting of the invention, and any obvious modifications will be apparent to one skilled in the art.  
       EXAMPLE 1  
       [0000]     Extraction may be carried out in one of the following three ways:  
         [0000]     Simple Extraction: Soak about ⅓ cup of fenugreek seeds in about 15 cups of water for 8-10 hours. Bring the mixture to a boil for about 5-7 minutes. Cool, strain and refrigerate the extracted “juice.” 
         [0000]     Quick Extraction: Combine about ⅓ cup fenugreek seeds in about 15 cups of water and bring to a boil for about 10 minutes. Cool, strain and refrigerate the extracted “juice.” 
         [0000]     Preferred Extraction: Grind about ⅓ cup of fenugreek seed to a powder. Combine the resulting powder with about 15 cups of water and bring to a boil for 10 minutes. Cool, strain and refrigerate the extracted “juice.” 
         [0025]     Note: The noted boiling times above are only preferred embodiments and may be considerably shorter or longer. Similarly, the proportion of seed to water employed may be scaled appropriately. The simple extraction method described above produces a slightly more opaque product. The best way to store fenugreek is to keep the seed in a cool and dry place. This allows for it to be kept for several months without loss in activity. Once the seed is ground or powdered, it does not keep well and must be used promptly. As soon as the “juice” is extracted, whether from the seed or the grind, it is preferred that it be kept refrigerated.  
       EXAMPLE 2  
       [0000]     Reconstitution of the extracted “Juice” may be accomplished by the following method:  
         [0026]     As stated earlier, while the exact composition of the final beverage may be in the form of the extracted “juice,” tea or carbonated beverage, a small quantity taken each day for 30 consecutive days provides a reduction in blood cholesterol of 30% or more. An individual serving of tea may be prepared by boiling a teaspoon of fresh powdered/ground fenugreek seed in a cup of water for ten minutes. Appropriate flavors, conventional carriers, excipients or additives may be additionally incorporated into the extracted “juice.” Examples include sweeteners (e.g., honey, sugar, aspartame, etc.) or flavors (e.g., lemon, anise, mint, etc.). Additionally, these beverages may be supplemented with various nutrients, vitamins, minerals, pharmaceutically active agents, fibers, liposomes and herbal extracts.  
         [0027]     It is understood that the invention is not limited to the disclosed compositions, methods of preparation and embodiments shown, including any embodiments that may be apparent to one of ordinary skill in the art. Although the foregoing invention has been described in some detail by way of illustration and examples for purposes of clarity of understanding, it will be readily apparent to those of ordinary skill in the art in light of the teachings of this invention that certain variations and modifications may be made thereto without departing from the spirit or scope of the disclosure herein, including the specific embodiments.