Abstract:
A process and formulation for a soft gel capsule that results in at least half the normal daily requirement of Coenzyme Q 10  being absorbed by a healthy human from a capsule having a reduced amount of Coenzyme Q 10 , GelOil SC, Vitamin E and an optional additional antioxidant.

Description:
FIELD OF THE INVENTION  
         [0001]    This invention relates to an improved formulation and process methodology of Coenzyme Q 10  for producing soft gel capsules with improved absorption.  
         BACKGROUND OF THE INVENTION  
         [0002]    Coenzyme Q 10  (CoQ 10  or Ubiquinone) is a large molecular weight (863.63 grams) lipid compound that is produced in the liver and perhaps other body organs. The total human body content is estimated to be 1.4 to 1.8 grams, depending on the age and the physical fitness of the individual. Although CoQ 10  is found in the mitochondria and other organelles of every living cell, it appears to be most abundant in tissues with a high number of mitochondria and a high level of metabolic activity. For example, in the metabolically inactive blood there is approximately 4 mg, in the heart, and in the skeletal muscle 1000 mg. The blood acts as a CoQ 10  reservoir and transport media between endogenous CoQ 10  synthesis in the liver, exogenous CoQ 10  absorption from digested food substances in the intestinal tract, and the body cells. Endogenous synthesis appears to be responsible for 56 percent and exogenous sources for 44 percent of the body is CoQ 10 , requirements. These numbers are currently being studied and endogenous CoQ 10  synthesis may be significantly deficient in the elderly. Furthermore, certain disease states, such as mitochondrial myopathy, and prescription drugs, such as cholesterol-lowering statin drugs, seem to deplete the endogenous CoQ 10  levels in the body. These deficiencies are not related to the total caloric intake, but rather to the vitamin content of ingested foods as the body requires multiple vitamins for the synthesis of CoQ 10 .  
           [0003]    CoQ 10  requirements of the body are also variable between individuals and are dependent on age, physical activity, and disease. It is estimated that the body CoQ 10  utilization is between 5 and 9 mg per day. Intercellular CoQ 10  is required for the synthesis of energy and therefore essential for life. Energy synthesis occurs in the mitochondria, where CoQ 10  provides an electron for the electron transport chain in the cytochrome system, in which adenosine tripohosphate (ATP) is synthesized. As CoQ 10  gives up an electron for ATP synthesis, it gets oxidized. If CoQ 10  is used as an antioxidant, it gets oxidized and is no longer available to provide electrons and function in the synthesis of ATP. Under conditions of high metabolic stress, endogenous sources may become inadequate to meet the body is CoQ 10  requirement for ATP synthesis. Under such conditions, dietary CoQ 10  supplementation has been shown to be an effective source. An improved soft gel formulation and process of CoQ 10  soft gel capsule manufacturing has used to treat heart failure, chronic fatigue and patients with psoriasis and planter warts. In all cases, it has been found that the improved soft gel formulation, at doses of 30-100 mg/day of CoQ 10 , have been proven to be superior to commercially available 60 mg dry powder capsules, and existing 100 mg/day CoQ 10  soft gel formulations.  
           [0004]    An appropriate CoQ 10  dosage for a normal individual compared to the dosage necessary for a diseased individual has been difficult to ascertain. Recommended doses of 10 to 30 mg/day were found to be ineffective for patients with significant CoQ 10  deficiencies. In the past 15 years, it has become generally accepted that poor intestinal absorption of certain CoQ 10  formulations limits their effective use. For this reason, 50 and 150 or even 200 mg tablets or capsules are commercially available to the consumer, at a considerable higher cost, the main cost driver being the CoQ 10 .  
           [0005]    Folkers et al. (U.S. Pat. No. 4,824,669) addresses a soft gel capsule with CoQ 10  and at least one vegetable oil. This formulation was determined to increase blood CoQ 10  levels to 2.5 μg/ml compared to 1.6 μg/ml for an equivalent 100 mg dose of dry powder CoQ 10 . Many different CoQ 10  formulations have appeared which are claimed to increase intestinal absorption. However, intestinal absorption data, collected under near basal conditions, which compare CoQ 10  alone in oil with dry powder CoQ 10 , are inconclusive.  
         SUMMARY OF THE INVENTION  
         [0006]    The present invention comprises a stable and nontoxic soft gel Coenzyme Q 10  formulation and process methodology of Coenzyme Q 10  for increased Coenzyme Q 10  absorption levels in the human intestinal tract. A preferred soft gel formulation includes Coenzyme Q 10  Gel Oil SC and Vitamin E (mixed tocopherols) added as a functional antioxidant. An additional ingredient, an antioxidant, may be added to this formula for additional antioxidant benefits. The preferred soft gel Coenzyme Q 10  formulation is administered twice a day in dosages of about 30 mg, thereby reducing the Coenzyme Q 10  cost while producing the desired retained Coenzyme Q 10 , in the human body.  
           [0007]    It is therefore an objective of the present invention to provide an improved soft gel formulation of CoQ 10  and a methodology of formulation processing that produce a significantly greater bioavailability of CoQ 10 , than existing soft or dry formulations. To this end, the present formulation contains CoQ 10  and refined soybean oil along with wetting and suspending agents derived from vegetables (GelOil SC) to improve the solubility of CoQ 10 . The composition of GelOil SC includes refined soybean oil (CAS# 8001-22-7), glycerides (mono-, di- and tri-glycerides of  16  to  18  carbon chain length) (CAS# 91052-54-9) and polyglycerol oleate (CAS# 9007-48-1). An additional antioxidant, either from natural or synthetic sources, can be added in order to prepare a potent combination antioxidant formulation.  
           [0008]    It is a further objective of the present invention to provide a soft gel formulation of CoQ 10  and methodology of administration that produces greater absorption in the intestine. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0009]    The unique formulation involves the following sequence of ingredients and process methodology.  
         [0010]    Heat GelOil SC to 25 to 35° C.;  
         [0011]    Simultaneously add in a container under vacuum the following ingredients to the heated GelOil SC:  
         [0012]    Coenzyme Q 10  Vitamin E, and if desired additional antioxidant in compatible form, the vacuum being to prevent oxidation of any of the ingredients;  
         [0013]    Blend and continuously stir of all the ingredients into a mixture;  
         [0014]    Cool the mixture to 25 to 30° C.;  
         [0015]    Mix the mixture within the container under a blanket of nitrogen gas to prevent oxidation of any of the ingredients; and  
         [0016]    Encapsulate the mixture in a soft gel capsule. If the cooled mixture sits for any length of time under its blanket of nitrogen before encapsulation, re-mix under the blanket of nitrogen to assure a homogeneous mixture for encapsulation.  
         [0017]    Typical amounts per capsule are:  
         [0018]    50 to 500 mg of GelOil SC;  
         [0019]    30 to 100 mg of Coenzyme Q 10 ;  
         [0020]    10-100 IU Vitamin E; and if desired  
         [0021]    0.5 to 500 mg of additional antioxidant.  
         [0022]    The bioavailability or intestinal absorption of CoQ 10  has been a major controversy in the international CoQ 10  research community. Previous data indicate that only 1 to 3% of a dry powder CoQ 10  formulation is absorbed through the lacteals in the intestines and appears in the blood over a twelve hour interval. In general, blood levels of 1.2 to 1.6 μg/ml have been reported, when taking 30 to 60 mg/day dry powder CoQ 10  formulation for 30 days. It has been reported that when a dry powder CoQ 10  formulation is taken with a fat, such as peanut butter, steady-state blood levels of 2.0 to 2.8 μg/ml are measurable. Multiple clinical trials were conducted in the United States and Europe using the Folkers (U.S. Pat. No. 4,824,669) soft gel. With a dosage of 100 mg/day multiple investigators have reported group mean blood levels of 2.3 to 3.5 μg/ml depending on the laboratory conducting the measurement.  
         [0023]    The present 30 mg CoQ 10  soft gel formulation of CoQ 10  provides approximately 50%, and with two capsules 100%, of the daily CoQ 10  requirements of a normal sedentary individual. It would take at least three of the dry powder 30 mg CoQ 10  capsules to produce the same effects as one of the present invention in 30 mg soft gel form, and six of the dry powder 30 mg CoQ 10  capsules to produce the same effect as two of the present 30 mg CoQ 10  soft gel capsules. Regardless of the absorption mechanism, the significantly higher basal blood CoQ 10  levels (167%) and the 273% greater absorption rate found in studies, establish that the present soft gel formulation is indeed a superior product to the dry CoQ 10  formulations. This may be especially true for those individuals whose daily CoQ 10  requirement is elevated due to: high physical activity; a need for CoQ 10  as an antioxidant; or active disease associated with known CoQ 10  deficiencies.  
         [0024]    Cellular CoQ 10  content is a function of the number and quality of the cellular mitochondria. For example, the failing heart muscle has 2.2 μg CoQ 10  per mg tissue and a blood CoQ 10  deficiency (0.3-0.5 μg/ml). The normal conditioned heart has 6.3 μg/gm in its tissue, and a low basal blood level (0.5-0.6 μg/ml). These results indicate that supplemental CoQ 10  enters the cell. This observation has also been reported for skeletal muscles of trained and non-trained athletes.  
         [0025]    The subjective and objective responses to supplemental CoQ 10  in the normal individual appear more rapidly compared to that of the physically unfit or the diseased individual with a CoQ 10  deficiency. The most probable reason for this observation is that the metabolic machinery (mitochondria) is viable in the non-diseased normal volunteer, whereas the mitochondria are atrophied in the cells of de-conditioned and diseased individuals. Therefore, it takes time in the diseased individual to build up the mitochondria to a more normal activity level and to normalize their distribution in the organ system involved.  
         [0026]    Thus there has been described a novel CoQ 10  formulation and method of formulation, which fulfill all the objects and advantages sought therefor. Many changes, modifications, variations and applications of the subject invention will become apparent to those skilled in the art after consideration of the specification.