U.S. patent application number 10/944992 was filed with the patent office on 2005-02-10 for formulation and manufacturing process for coenzyme q10 soft gel capsules.
Invention is credited to Hari, Siva P., Naguib, Yousry M.A., Udell, Ronalds G..
Application Number | 20050031681 10/944992 |
Document ID | / |
Family ID | 34119694 |
Filed Date | 2005-02-10 |
United States Patent
Application |
20050031681 |
Kind Code |
A1 |
Udell, Ronalds G. ; et
al. |
February 10, 2005 |
Formulation and manufacturing process for Coenzyme Q10 soft gel
capsules
Abstract
A soft gelatine capsule formulation improved manufacturing of
Coenzyme Q10, comprising Coenzyme Q10 in a thixotropic gelatine
carrier capable of admixing without heating with Coenzyme Q10, and
capable of keeping Coenzyme Q10 in suspension at ambient
temperature.
Inventors: |
Udell, Ronalds G.; (Beverly
Hills, CA) ; Naguib, Yousry M.A.; (Arcadia, CA)
; Hari, Siva P.; (Irvine, CA) |
Correspondence
Address: |
Scott D. Rothenberger, Esq.
DORSEY & WHITNEY LLP
Intellectual Property Department
50 South Sixth Street Suite 500
Minneapolis
MN
55402-1498
US
|
Family ID: |
34119694 |
Appl. No.: |
10/944992 |
Filed: |
September 20, 2004 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
10944992 |
Sep 20, 2004 |
|
|
|
10368260 |
Feb 18, 2003 |
|
|
|
10368260 |
Feb 18, 2003 |
|
|
|
09873156 |
Jun 1, 2001 |
|
|
|
60263953 |
Jan 24, 2001 |
|
|
|
Current U.S.
Class: |
424/456 ;
424/94.1; 514/690 |
Current CPC
Class: |
A23V 2002/00 20130101;
A61K 31/122 20130101; A61K 31/355 20130101; A23L 33/10 20160801;
A23V 2250/182 20130101; A61K 2300/00 20130101; A61K 2300/00
20130101; A61K 9/4858 20130101; A61K 31/122 20130101; A23V 2002/00
20130101; A23V 2250/194 20130101; A23V 2250/314 20130101; A23V
2250/712 20130101; A61K 45/06 20130101; A61K 31/355 20130101; Y10S
514/962 20130101; A23V 2250/192 20130101 |
Class at
Publication: |
424/456 ;
424/094.1; 514/690 |
International
Class: |
A61K 038/43; A61K
009/64; A61K 031/12 |
Claims
What is claimed is:
1. A composition comprising Coenzyme Q10 in combination with an
antioxidant in a thixatropic gelatine carrier for manufacturing
soft gel capsules at a temperature of about 27.degree. C. to about
30.degree. C. containing a stable uniform suspension of Coenzyme
Q10.
2. A soft gel capsule comprising Coenzyme Q10 and a thixatropic
gelatine carrier.
3. The soft gel capsule of claim 2, wherein the thixatropic
gelatine carrier is a semi-solid at a temperature of about
23.degree. C. to about 28.degree. C. and becomes fluid when
stirred.
4. The soft gel capsule of claim 2, wherein the thixatropic
gelatine carrier comprises: from about 84% to about 95% vegetable
oil selected from the group consisting of soybean oil, rapeseed
oil, palm oil, and cotton seed oil; from about 1% to about 9% of a
viscosity modifier selected from the group consisting of a glyceryl
palmito stearate and glyceryl behenate; and from about 1% to about
15% of a surface active agent comprising polyglyceryl oleate.
5. The soft gel capsule of claim 2, wherein the amount of Coenzyme
Q10 in the soft gel capsule ranges from 8 to 40% by weight.
6. A process of manufacturing a soft gel capsule comprising
Coenzyme Q10, said process comprising the steps of: (a) stirring a
thixatropic gelatine carrier until the thixatropic gelatine carrier
is liquefied; (b) adding Coenzyme Q10 to the liquefied carrier to
form a mixture; and (c) encapsulating the mixture in a soft gel
capsule.
7. The process of claim 6, wherein the thixatropic gelatine carrier
comprises: from about 84% to about 95% vegetable oil selected from
the group consisting of soybean oil, rapeseed oil, palm oil, and
cotton seed oil; from about 1% to about 9% of a viscosity modifier
selected from the group consisting of a glyceryl palmito stearate
and glyceryl behenate; and from about 1% to about 15% of a surface
active agent comprising polyglyceryl oleate.
8. The process of claim 6, further comprising the step of heating
the thixatropic gelatine carrier from about 27.degree. C. to about
30.degree. C. prior to the addition of the Coenzyme Q10.
9. The process of claim 6, wherein 30 to 100 mg of the Coenzyme Q10
are in each capsule.
10. The process of claim 6, wherein the mixture is cooled from
about 23.degree. C. to 28.degree. C.
11. The process of claim 6, wherein 50 to 500 mg of the thixatropic
gelatine carrier is in each capsule.
12. A soft gel capsule, prepared by a process comprising the steps
of: (a) heating a thixatropic gelatine carrier to a temperature
that liquefies the carrier; (b) blending the heated thixatropic
gelatine carrier and Coenzyme Q10; (c) cooling the blended mixture
to a temperature, thereby causing the mixture to form a viscous
semi-solid; and (e) encapsulating the mixed, cooled mixture in a
soft gel capsule.
13. The soft gel capsule prepared by the process of claim 12,
wherein the thixatropic gelatine carrier comprises: from about 84%
to about 95% vegetable oil selected from the group consisting of
soybean oil, rapeseed oil, palm oil, and cotton seed oil; from
about 1% to about 9% of a viscosity modifier selected from the
group consisting of a glyceryl palmito stearate and glyceryl
behenate; and from about 1% to about 15% of a surface active agent
comprising polyglyceryl oleate.
14. The soft gel capsule prepared by the process of claim 12,
wherein the thixatropic gelatine carrier is heated from about
27.degree. C. to about 30.degree. C.
15. The soft gel capsule prepared by the process of claim 12,
wherein 30 to 100 mg of the Coenzyme Q10 are in each capsule.
16. The soft gel capsule prepared by the process of claim 12,
wherein the mixture is cooled from about 23.degree. C. to
28.degree. C.
17. The soft gel capsule prepared by the process of claim 12,
wherein 50 to 500 mg of the thixatropic gelatine carrier is in each
capsule.
18. A process of manufacturing a soft gel capsule comprising
Coenzyme Q10, said process comprising the steps of: (a) mixing a
thixatropic gelatine carrier and Coenzyme Q10 to form a mixture;
and (b) encapsulating the mixture in a soft gel capsule.
19. The process of claim 18, wherein the thixatropic gelatine
carrier comprises: from about 84% to about 95% vegetable oil
selected from the group consisting of soybean oil, rapeseed oil,
palm oil, and cotton seed oil; from about 1% to about 9% of a
viscosity modifier selected from the group consisting of a glyceryl
palmito stearate and glyceryl behenate; and from about 1% to about
15% of a surface active agent comprising polyglyceryl oleate.
20. The process of claim 18, further comprising the step of heating
the mixture from about 27.degree. C. to about 30.degree. C.
21. The process of claim 18, wherein 30 to 100 mg of the Coenzyme
Q10 are in each capsule.
22. The process of claim 18, wherein the mixture is cooled from
about 23.degree. C. to 28.degree. C.
23. The process of claim 18, wherein 50 to 500 mg of the
thixatropic gelatine carrier is in each capsule.
24. A process of manufacturing a soft gel capsule comprising
Coenzyme Q10, said process comprising the steps of: (a) stirring a
thixatropic gelatine carrier until the thixatropic gelatine carrier
is liquefied; (b) adding Coenzyme Q10 and an antioxidant to the
liquefied carrier to form a mixture; and (c) encapsulating the
mixture in a soft gel capsule.
25. The process of claim 24, wherein the thixatropic gelatine
carrier comprises: from about 84% to about 95% vegetable oil
selected from the group consisting of soybean oil, rapeseed oil,
palm oil, and cotton seed oil; from about 1% to about 9% of a
viscosity modifier selected from the group consisting of a glyceryl
palmito stearate and glyceryl behenate; and from about 1% to about
15% of a surface active agent comprising polyglyceryl oleate.
26. The process of claim 24, further comprising the step of heating
the thixatropic gelatine carrier from about 27.degree. C. to about
30.degree. C. prior to the addition of the Coenzyme Q10 and
antioxidant.
27. The process of claim 24, wherein 30 to 100 mg of the Coenzyme
Q10 are in each capsule.
28. The process of claim 24, wherein 10 to 100 mg of the
antioxidant are in each capsule.
29. The process of claim 28, wherein the antioxidant is vitamin
E.
30. The process of claim 24, wherein the mixture is cooled from
about 23.degree. C. to 28.degree. C.
31. The process of claim 24, wherein 50 to 500 mg of the
thixatropic gelatine carrier is in each capsule.
Description
[0001] This is a Continuation of U.S. application Ser. No.
10/368,260 filed on Feb. 18, 2003, which is a Continuation-In-Part
of U.S. application Ser. No. 09/873,156 which was filed Jun. 1,
2001, now abandoned, that in turn claims priority benefit of U.S.
Provisional Application Ser. No. 60/263,953 filed Jan. 24, 201, the
contents of which are incorporated herein in their entirety.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] This invention relates to a composition and process of
manufacturing Coenzyme Q10 with improved human absorption
characteristics in a thixotropic gelatin carrier capable of
admixing without heating the Coenzyme Q10, and capable of
suspending Coenzyme Q10 in a uniform dispersion.
[0004] 2. Background go of the Invention
[0005] Coenzyme Q10 (CoQ10 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 CoQ10 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, there is
approximately 4 mg of CoQ10 in the heart tissues, and about 1000 mg
in the skeletal muscle. The blood acts as a CoQ10 reservoir and
transport media between endogenous CoQ10 synthesis in the
intestinal liver, exogenous CoQ10 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's CoQ10 requirements. These
numbers are currently being studied and endogenous CoQ10 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 CoQ10 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 CoQ10.
[0006] CoQ10 requirements of the body are also variable between
individuals and are dependent on age, physical activity, and
disease. It is estimated that the body CoQ10 utilization is between
5 and 9 mg per day. Intercellular CoQ10 is required for the
synthesis of energy and therefore essential for life. Energy
synthesis occurs in the mitochondria, where CoQ10 provides an
electron for the electron transport chain in the cytochrome system,
in which adenosine triphosphate (ATP) is synthesized. As CoQ10
gives up an electron for the ATP synthesis, it gets oxidized. If
CoQ10 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's CoQ10 requirement for ATP
synthesis. Under such conditions, dietary CoQ10 supplementation has
been shown to be an effective source. CoQ10 has been 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 CoQ10, have been
proven to be superior to commercially available 60 mg dry powder
capsules, and existing 100 mg/day CoQ10 soft gel formulations.
[0007] An appropriate CoQ10 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 CoQ10
deficiencies. In the past 15 years, it has become generally
accepted that poor intestinal absorption of certain CoQ10
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 CoQ10.
[0008] Folkers et al. (U.S. Pat. No. 4,824,669) addresses a soft
gel capsule with CoQ10 and at least one vegetable oil. This
formulation was determined to increase blood CoQ10 levels to 2.5
.mu.g/ml compared to 1.6 .mu.g/ml for an equivalent 100 mg dose of
dry powder CoQ10. Many different CoQ10 formulations have appeared
which are claimed to increase intestinal absorption. However,
intestinal absorption data, collected under near basal conditions,
which compare CoQ10 alone in oil with dry powder CoQ10, are
inconclusive.
SUMMARY OF THE INVENTION
[0009] The present invention comprises a formulation of Coenzyme
Q10 for improved manufacturing of soft gelatine capsules containing
Coenzyme Q10.
[0010] According to the present invention, a preferred soft gel
formulation includes Coenzyme Q10, Vitamin E (mixed tocopherols)
added as a functional antioxidant, and a thixatropic gelatin
carrier which has the ability of enhancing the solubility and
stability of the active ingredient and provides for better
absorption thereof in humans. An additional ingredient, an
antioxidant, either from natural or synthetic sources, can be added
in order to prepare a potent combination antioxidant formulation.
The preferred soft gel Coenzyme Q10 formulation is administered
twice a day in dosages of about 30 mg, thereby reducing the
Coenzyme Q10 cost while producing the desired retained Coenzyme Q10
in the human body.
[0011] Other features and advantages of the present invention will
become more apparent from the following detailed description, which
illustrate, byway of example, the principles of the invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0012] The present invention utilizes a gelatine carrier with
thixatropic properties and substantial capacity to suspend active
ingredients in a uniform dispersion. The carrier composition used
in the present invention is described in U.S. Pat. No. 6,365,181
(issued to Matthews), and is a thixatropic carrier gel comprising a
homogeneous dispersion of viscosity modifiers and surface active
agents in vegetable oil. When the carrier composition is agitated,
such as by slow stirring, it becomes fluid, and when the agitation
is stopped, it becomes a highly viscous semi-solid. Active agents
are easily admixed with the carrier composition by stirring and
high loadings of the active agents can be used to make a stable
uniform dispersion within the carrier composition because the
composition becomes semi-solid when stirring is stopped.
[0013] As described in the Matthews patent, the components of the
carrier composition include from about 84% to 95% of a vegetable
oil, from about 1% to 9% of a viscosity modifier, and from about 1%
to 15% of a surface active agent such that the total amounts to
100%. Other details of the thixatropic gelatine carrier used in the
present invention are described in the Matthews patent, and are
incorporated herein by reference.
[0014] The unique formulation of the present invention involves the
following sequence of ingredients and process methodology:
[0015] (A) Heat the thixatropic gelatine carrier to a temperature
of about 25.degree. C. to about 35.degree. C. (preferably about
27.degree. C. to about 30.degree. C.);
[0016] (B) Simultaneously add in a container under vacuum the
following ingredients to the pre-heated thixatropic gelatine
carrier: Coenzyme Q10, Vitamin E, and if desired, additional
antioxidant in compatible form, the vacuum being to prevent
oxidation of any of the ingredients;
[0017] (C) Blend and continuously stir all of the ingredients into
a mixture;
[0018] (D) Cool the mixture to a temperature of about 23.degree. C.
to 28.degree. C. (preferably about 25.degree. C.);
[0019] (E) Mix the mixture within the container under a blanket of
nitrogen gas to prevent oxidation of any of the ingredients;
and
[0020] (F) Encapsulate the mixture in a soft gel capsule.
[0021] 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 homogenous mixture for encapsulation.
[0022] Typical amounts of ingredients per capsule are:
[0023] -50 to 500 mg of the thixatropic gelatine carrier, described
above;
[0024] -30 to 100 mg of Coenzyme Q10;
[0025] -10 to 100 IU Vitamin E; and if desired
[0026] -0.5 to 500 mg of additional antioxidant.
[0027] The bioavailability or intestinal absorption of CoQ10 has
been a major controversy in the international CoQ10 research
community. Previous data indicate that only 1 to 3% of a dry powder
CoQ10 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 .mu.g/ml have been reported,
when taking 30 to 60 mg/day dry powder CoQ10 formulation for 30
days. It has been reported that when a dry powder CoQ10 formulation
is taken with a fat, such a peanut butter, steady-state blood
levels of 2.0 to 2.8 .mu.g/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 .mu.g/ml depending on the laboratory conducting the
measurement.
[0028] The present invention's 30 mg CoQ10 soft gel formulation of
CoQ10 provides approximately 50%, and with two capsules 100%, of
the daily CoQ10 requirements of a normal sedentary individual. It
would take at least three of the dry powder 30 mg CoQ10 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 CoQ10 capsules to
produce the same effect as two of the present invention 30 mg CoQ10
soft gel capsules.
[0029] Regardless of the absorption mechanism, the significantly
higher basal blood CoQ10 levels (167%) and the 273% greater
absorption rate found in studies, establish that the present
invention soft gel formulation is indeed a superior product to the
dry powder CoQ10 formulations. This may be especially true for
those individuals whose daily CoQ10 requirement is elevated due to:
high physical activity; a need for CoQ10 as an antioxidant; or
active disease associated with known CoQ10 deficiencies.
[0030] Cellular CoQ10 content is a function of the number and
quality of the cellular mitochondria. For example, the failing
heart muscle has 2.2 .mu.g CoQ10 per mg tissue and a blood CoQ10
deficiency (0.3-0.5 .mu.g/ml). The normal conditioned heart has 6.3
.mu.g/gm in its tissue, and a low basal blood level (0.5-0.6
.mu.g/ml). These results indicate that supplemental CoQ10 enters
the cell. This observation has also been reported for skeletal
muscles of trained and non-trained athletes.
[0031] The subjective and objective responses to supplemental CoQ10
in the normal individual appear more rapidly compared to that of
the physically unfit or the diseased individual with a CoQ10
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.
[0032] Thus, there has been described a novel CoQ10 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. All
such changes, modifications, alterations and other uses and
applications which do not depart from the spirit and scope of the
invention are deemed to be covered by the invention which is
limited only by the claims that follow.
* * * * *