U.S. patent application number 10/073978 was filed with the patent office on 2002-08-15 for ultrafine l-carnitine, methods of preparing the same, compositions containing the same, and methods of using the same.
This patent application is currently assigned to Sigma-Tau HealthScience S.p.A.. Invention is credited to Hassen, Ken.
Application Number | 20020111383 10/073978 |
Document ID | / |
Family ID | 26849378 |
Filed Date | 2002-08-15 |
United States Patent
Application |
20020111383 |
Kind Code |
A1 |
Hassen, Ken |
August 15, 2002 |
Ultrafine L-carnitine, methods of preparing the same, compositions
containing the same, and methods of using the same
Abstract
L-carnitine which has a particle size such that it substantially
passes through a 100 USBS mesh sieve exhibits an increased
bioavailability, a decreased hygroscopicity, and may be
conveniently formulated with oil-based materials.
Inventors: |
Hassen, Ken; (Malvern,
PA) |
Correspondence
Address: |
OBLON SPIVAK MCCLELLAND MAIER & NEUSTADT PC
FOURTH FLOOR
1755 JEFFERSON DAVIS HIGHWAY
ARLINGTON
VA
22202
US
|
Assignee: |
Sigma-Tau HealthScience
S.p.A.
Pomezia RM
IT
|
Family ID: |
26849378 |
Appl. No.: |
10/073978 |
Filed: |
February 14, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10073978 |
Feb 14, 2002 |
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09653861 |
Sep 1, 2000 |
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60152240 |
Sep 3, 1999 |
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60158245 |
Oct 8, 1999 |
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Current U.S.
Class: |
514/547 ; 514/23;
514/561 |
Current CPC
Class: |
A23V 2002/00 20130101;
A61P 3/00 20180101; A23L 33/175 20160801; A61K 31/205 20130101;
A61K 9/14 20130101; A61P 9/00 20180101; A61P 3/04 20180101; A61P
3/06 20180101; A23V 2002/00 20130101; A23V 2250/0612 20130101 |
Class at
Publication: |
514/547 ;
514/561; 514/23 |
International
Class: |
A61K 031/225; A61K
031/198; A61K 031/70 |
Claims
What is claimed as new and desired to be secured by Letters Patent
of the United States is:
1. L-carnitine, having a particle size such that it substantially
passes through a 100 USBS mesh sieve.
2. The L-carnitine of claim 1, which is selected from the group
consisting of L-carnitine, salts of L-carnitine, alkanoyl
L-carnitines, and salts of alkanoyl L-carnitine .
3. The L-carnitine of claim 1, which is selected from the group
consisting of L-carnitine chloride, L-carnitine bromide,
L-carnitine orotate, L-carnitine acid aspartate, L-carnitine acid
phosphate, L-carnitine fumarate, L-carnitine lactate, L-carnitine
maleate, L-carnitine acid maleate, L-carnitine acid oxalate,
L-carnitine acid sulfate, L-carnitine glucose phosphate,
L-carnitine tartrate, L-carnitine acid tartrate, L-carnitine
iodate, L-carnitine aspartate, L-carnitine citrate, L-carnitine
acid citrate, L-carnitine acid fumarate, L-carnitine
glycerophosphate, L-carnitine mucate, L-carnitine orotate,
L-carnitine oxalate, L-carnitine sulfate, L-carnitine
trichloroacetate, L-carnitine trifluoroacetate, L-carnitine
methanesulfonate, L-carnitine pamoate, L-carnitine acid pamoate,
C.sub.2-8 alkanoyl L-carnitines, C.sub.2-8 alkanoyl L-carnitine
chloride, C.sub.2-8 alkanoyl L-carnitine bromide, C.sub.2-8
alkanoyl L-carnitine orotate, C.sub.2-8 alkanoyl L-carnitine acid
aspartate, C.sub.2-8 alkanoyl L-carnitine acid phosphate, C.sub.2-8
alkanoyl L-carnitine fumarate, C.sub.2-8 alkanoyl L-carnitine
lactate, C.sub.2-8 alkanoyl L-carnitine maleate, C.sub.2-8,
alkanoyl L-carnitine acid maleate, C.sub.2-8 alkanoyl L-carnitine
acid oxalate, C.sub.2-8 alkanoyl L-carnitine acid sulfate,
C.sub.2-8 alkanoyl L-carnitine glucose phosphate, C.sub.2-8
alkanoyl L-carnitine tartrate, C.sub.2-8, alkanoyl L-carnitine acid
tartrate, C.sub.2-8, alkanoyl L-carnitine iodate, C.sub.2-8
alkanoyl L-carnitine aspartate, C.sub.2-8 alkanoyl L-carnitine
citrate, C.sub.2-8 alkanoyl L-carnitine acid citrate, C.sub.2-8
alkanoyl L-carnitine acid fimarate, C.sub.2-8 alkanoyl L-carnitine
glycerophosphate, C.sub.2-8 alkanoyl L-carnitine mucate, C.sub.2-8
alkanoyl L-carnitine orotate, C.sub.2-8 alkanoyl L-carnitine
oxalate, C.sub.2-8 alkanoyl L-carnitine sulfate, C.sub.2-8 alkanoyl
L-carnitine trichloroacetate, C.sub.2-8 alkanoyl L-carnitine
trifluoroacetate, C.sub.2-8 alkanoyl L-carnitine methanesulfonate,
C.sub.2-8 alkanoyl L-carnitine pamoate, and C.sub.2-8 alkanoyl
L-carnitine acid pamoate.
4. A method of preparing L-carnitine, having a particle size such
that it substantially passes through a 100 USBS mesh sieve,
comprising: (1) subjecting L-carnitine having a particle size such
that it does not pass through a 100 USBS mesh sieve to size
reduction, to obtain size-reduced L-carnitine; and (2) subjecting
said size-reduced L-carnitine to sieving through a 100 USBS mesh
sieve and selecting that portion which passes through said 100 USBS
mesh sieve.
5. The method of claim 4, wherein said L-carnitine is selected from
the group consisting of L-carnitine, salts of L-carnitine, alkanoyl
L-carnitines, and salts of alkanoyl L-carnitine.
6. The method of claim 4, wherein said L-carnitine is selected from
the group consisting of L-carnitine chloride, L-carnitine bromide,
L-carnitine orotate, L-carnitine acid aspartate, L-carnitine acid
phosphate, L-carnitine fumarate, L-carnitine lactate, L-carnitine
maleate, L-carnitine acid maleate, L-carnitine acid oxalate,
L-carnitine acid sulfate, L-carnitine glucose phosphate,
L-carnitine tartrate, L-carnitine acid tartrate, L-carnitine
iodate, L-carnitine aspartate, L-carnitine citrate, L-carnitine
acid citrate, L-carnitine acid fumarate, L-carnitine
glycerophosphate, L-carnitine mucate, L-carnitine orotate,
L-carnitine oxalate, L-carnitine sulfate, L-carnitine
trichloroacetate, L-carnitine trifluoroacetate, L-carnitine
methanesulfonate, L-carnitine pamoate, L-carnitine acid pamoate,
C.sub.2-8 alkanoyl L-carnitines, C.sub.2-8 alkanoyl L-carnitine
chloride, C.sub.2-8 alkanoyl L-carnitine bromide, C.sub.2-8
alkanoyl L-carnitine orotate, C.sub.2-8 alkanoyl L-carnitine acid
aspartate, C.sub.2-8 alkanoyl L-carnitine acid phosphate, C.sub.2-8
alkanoyl L-carnitine fumarate, C.sub.2-8 alkanoyl L-carnitine
lactate, C.sub.2-8 alkanoyl L-carnitine maleate, C.sub.2-8 alkanoyl
L-carnitine acid maleate, C.sub.2-8 alkanoyl L-carnitine acid
oxalate, C.sub.2-8 alkanoyl L-carnitine acid sulfate, C.sub.2-8,
alkanoyl L-carnitine glucose phosphate, C.sub.2-8 alkanoyl
L-carnitine tartrate, C.sub.2-8 alkanoyl L-carnitine acid tartrate,
C.sub.2-8 alkanoyl L-carnitine iodate, C.sub.2-8 alkanoyl
L-carnitine aspartate, C.sub.2-8 alkanoyl L-carnitine citrate,
C.sub.2-8 alkanoyl L-carnitine acid citrate, C.sub.2-8 alkanoyl
L-carnitine acid fumarate, C.sub.2-8 alkanoyl L-carnitine
glycerophosphate, C.sub.2-8 alkanoyl L-carnitine mucate, C.sub.2-8
alkanoyl L-carnitine orotate, C.sub.2-8 alkanoyl L-carnitine
oxalate, C.sub.2-8 alkanoyl L-carnitine sulfate, C.sub.2-8 alkanoyl
L-carnitine trichloroacetate, C.sub.2-8 alkanoyl L-carnitine
trifluoroacetate, C.sub.2-8 alkanoyl L-carnitine methanesulfonate,
C.sub.2-8 alkanoyl L-carnitine pamoate, and C.sub.2-8 alkanoyl
L-carnitine acid pamoate.
7. A composition, comprising: (A) L-carnitine having a particle
size such that it substantially passes through a 100 USBS mesh
sieve; and (B) a pharmaceutically acceptable excipient or
carrier.
8. The composition of claim 7, wherein said L-carnitine is selected
from the group consisting of L-carnitine, salts of L-carnitine,
alkanoyl L-carnitines, and salts of alkanoyl L-carnitine.
9. The composition of claim 7, wherein said L-carnitine is selected
from the group consisting of L-carnitine chloride, L-carnitine
bromide, L-carnitine orotate, L-carnitine acid aspartate,
L-carnitine acid phosphate, L-carnitine fumarate, L-carnitine
lactate, L-carnitine maleate, L-carnitine acid maleate, L-carnitine
acid oxalate, L-carnitine acid sulfate, L-carnitine glucose
phosphate, L-carnitine tartrate, L-carnitine acid tartrate,
L-carnitine iodate, L-carnitine aspartate, L-carnitine citrate,
L-carnitine acid citrate, L-carnitine acid fumarate, L-carnitine
glycerophosphate, L-carnitine mucate, L-carnitine orotate,
L-carnitine oxalate, L-carnitine sulfate, L-carnitine
trichloroacetate, L-carnitine trifluoroacetate, L-carnitine
methanesulfonate, L-carnitine pamoate, L-carnitine acid pamoate,
C.sub.2-8 alkanoyl L-carnitines, C.sub.2-8 alkanoyl L-carnitine
chloride, C.sub.2-8 alkanoyl L-carnitine bromide, C.sub.2-8
alkanoyl L-carnitine orotate, C.sub.2-8 alkanoyl L-carnitine acid
aspartate, C.sub.2-8 alkanoyl L-carnitine acid phosphate, C.sub.2-8
alkanoyl L-carnitine fumarate, C.sub.2-8 alkanoyl L-carnitine
lactate, C.sub.2-8 alkanoyl L-carnitine maleate, C.sub.2-8 alkanoyl
L-carnitine acid maleate, C.sub.2-8 alkanoyl L-carnitine acid
oxalate, C.sub.2-8 alkanoyl L-carnitine acid sulfate, C.sub.2-8
alkanoyl L-carnitine glucose phosphate, C.sub.2-8 alkanoyl
L-carnitine tartrate, C.sub.2-8 alkanoyl L-carnitine acid tartrate,
C.sub.2-8 alkanoyl L-carnitine iodate, C.sub.2-8 alkanoyl
L-carnitine aspartate, C.sub.2-8 alkanoyl L-carnitine citrate,
C.sub.2-8 alkanoyl L-carnitine acid citrate, C.sub.2-8 alkanoyl
L-carnitine acid fumarate, C.sub.2-8 alkanoyl L-carnitine
glycerophosphate, C.sub.2-8 alkanoyl L-carnitine mucate, C.sub.2-8
alkanoyl L-carnitine orotate, C.sub.2-8 alkanoyl L-carnitine
oxalate, C.sub.2-8 alkanoyl L-carnitine sulfate, C.sub.2-8,
alkanoyl L-carnitine trichloroacetate, C.sub.2-8 alkanoyl
L-carnitine trifluoroacetate, C.sub.2-8 alkanoyl L-carnitine
methanesulfonate, C.sub.2-8 alkanoyl L-carnitine pamoate, and
C.sub.2-8 alkanoyl L-carnitine acid pamoate.
10. The composition of claim 7, which is suitable for oral
ingestion.
11. The composition of claim 7, which further comprises
hydroxycitric acid, Co-enzyme Q10, chromium picolinate, gamma
linolenic acid, resveratrol, omega 3 acids, an antioxidant, or a
vitamin.
12. In a method of treatment, therapy, or prevention, comprising
orally administering an effective amount of L-carnitine to a
subject in need thereof, the improvement being said L-carnitine has
a particle size such that it substantially passes through a 100
USBS mesh sieve.
13. The method of claim 12, wherein said L-carnitine is selected
from the group consisting of L-carnitine, salts of L-carnitine,
alkanoyl L-carnitines, and salts of alkanoyl L-carnitine.
14. The method of claim 12, wherein said L-carnitine is selected
from the group consisting of L-carnitine chloride, L-carnitine
bromide, L-carnitine orotate, L-carnitine acid aspartate,
L-carnitine acid phosphate, L-carnitine fumarate, L-carnitine
lactate, L-carnitine maleate, L-carnitine acid maleate, L-carnitine
acid oxalate, L-carnitine acid sulfate, L-carnitine glucose
phosphate, L-carnitine tartrate, L-carnitine acid tartrate,
L-carnitine iodate, L-carnitine aspartate, L-carnitine citrate,
L-carnitine acid citrate, L-carnitine acid fumarate, L-carnitine
glycerophosphate, L-carnitine mucate, L-carnitine orotate,
L-carnitine oxalate, L-carnitine sulfate, L-carnitine
trichloroacetate, L-carnitine trifluoroacetate, L-carnitine
methanesulfonate, L-carnitine pamoate, L-carnitine acid pamoate,
C.sub.2-8 alkanoyl L-carnitines, C.sub.2-8-alkanoyl L-carnitine
chloride, C.sub.2-8 alkanoyl L-carnitine bromide, C.sub.2-8
alkanoyl L-carnitine orotate, C.sub.2-8 alkanoyl L-carnitine acid
aspartate, C.sub.2-8 alkanoyl L-carnitine acid phosphate, C.sub.2-8
alkanoyl L-carnitine fumarate, C.sub.2-8 alkanoyl L-carnitine
lactate, C.sub.2-8 alkanoyl L-carnitine maleate, C.sub.2-8 alkanoyl
L-carnitine acid maleate, C.sub.2-8 alkanoyl L-carnitine acid
oxalate, C.sub.2-8 alkanoyl L-carnitine acid sulfate, C.sub.2-8
alkanoyl L-carnitine glucose phosphate, C.sub.2-8 alkanoyl
L-carnitine tartrate, C.sub.2-8 alkanoyl L-carnitine acid tartrate,
C.sub.2-8 alkanoyl L-carnitine iodate, C.sub.2-8 alkanoyl
L-carnitine aspartate, C.sub.2-8 alkanoyl L-carnitine citrate,
C.sub.2-8, alkanoyl L-carnitine acid citrate, C.sub.2-8 alkanoyl
L-carnitine acid fumarate, C.sub.2-8 alkanoyl L-carnitine
glycerophosphate, C.sub.2-8 alkanoyl L-carnitine mucate, C.sub.2-8
alkanoyl L-carnitine orotate, C.sub.2-8 alkanoyl L-carnitine
oxalate, C.sub.2-8 alkanoyl L-carnitine sulfate, C.sub.2-8 alkanoyl
L-carnitine trichloroacetate, C.sub.2-8 alkanoyl L-carnitine
trifluoroacetate, C.sub.2-8 alkanoyl L-carnitine methanesulfonate,
C.sub.2-8 alkanoyl L-carnitine pamoate, and C.sub.2-8 alkanoyl
L-carnitine acid pamoate.
Description
[0001] This application claims priority to U.S. Provisional
Application No. 60/152,240 filed on Sep. 3, 1999, and U.S.
Provisional Application No. 60/158,245 filed on Oct. 8, 1999.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates to an ultra-fine L-carnitine
and salts thereof. In particular, the present invention relates to
L-carnitine and salts thereof which exist in the form of ultra-fine
particles. The present ultra-fine L-carnitine is capable of being
uniformly blended with fine particles of other raw materials, while
maintaining its own discrete shape. The overall fineness of the
present ultra-fine L-carnitine makes it ideal for blending with
oil-based raw materials with which conventional bulk carnitine is
not entirely miscible. The overall fineness of the present
ultra-fine L-carnitine also facilitates the ready absorption in the
gut due to the increased overall surface area of the fine material.
The present invention also relates to methods for preparing such
ultra-fine L-carnitine and salts thereof. The present invention
further relates to compositions which comprise such ultra-fine
L-carnitine and salts thereof. The present invention additionally
relates to methods of using such ultra-fine L-carnitine and salts
thereof.
[0004] 2. Description of the Background
[0005] L-carnitine is known to have many uses. In particular, the
oral administration of L-carnitine has been shown to be an
effective therapy for cardiovascular diseases. L-carnitine and its
salts are also known to be useful as dietary supplements, in
particular for the facilitation of the metabolism of lipids.
[0006] However, it is desired to increase the bioavailability of
L-Carnitine and its well known salts. It is also desired to prepare
compositions which contain L-carnitine and one or more other
ingredients with which bulk L-carnitine is not miscible, e.g.,
oil-based raw materials. It is further desired to reduce the
hygroscopicity of L-carnitine.
[0007] Thus, there remains a need for forms of L-carnitine and
salts thereof which exhibit increased bioavailability upon oral
administration. There also remains a need for forms of L-carnitine
and salts thereof which can be easily formulated with other
ingredients with which bulk L-carnitine is not miscible, e.g.,
oil-based raw materials. There also remains a need for forms of
L-carnitine and salts thereof which exhibit a decreased
hygroscopicity.
SUMMARY OF THE INVENTION
[0008] Accordingly, it is one object of the present invention to
provide novel forms of L-carnitine and salts thereof which exhibit
an increased bioavailability upon oral administration.
[0009] It is another object of the present invention to provide
novel forms of L-carnitine and salts thereof which can be easily
formulated with other ingredients with which bulk L-carnitine is
not miscible, e.g., oil-based raw materials.
[0010] It is another object of the present invention to provide
novel forms of L-carnitine and salts thereof which exhibit a
reduced hygroscopicity.
[0011] It is another object of the present invention to provide
novel methods of preparing such L-carnitine.
[0012] It is another object of the present invention to provide
novel compositions which contain such L-carnitine.
[0013] It is another object of the present invention to provide
novel methods of using such L-carnitine.
[0014] These and other objects, which will become apparent during
the following detailed description, have been achieved by the
inventors' discovery that L-carnitine and salts thereof which exist
in the form of ultra-fine particles exhibit a high bioavailability
upon oral administration. The inventors have also discovered that
such L-carnitine may be conveniently formulated with oil-based raw
materials. The inventors have also discovered that such L-carnitine
exhibits a reduced hygroscopicity.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0015] Thus, in a first embodiment, the present invention provides
ultra-fine L-carnitine and salts thereof. In the context of the
present invention, the term L-carnitine and salts thereof includes
not only L-carnitine itself, but also salts of L-carnitine ,
alkanoyl L-carnitines, and salts of alkanoyl L-carnitine. Suitable
salts of L-carnitine include L-carnitine chloride, L-carnitine
bromide, L-carnitine orotate, L-carnitine acid aspartate,
L-carnitine acid phosphate, L-carnitine fumarate, L-carnitine
lactate, L-carnitine maleate, L-carnitine acid maleate, L-carnitine
acid oxalate, L-carnitine acid sulfate, L-carnitine glucose
phosphate, L-carnitine tartrate, L-carnitine acid tartrate,
L-carnitine iodate, L-carnitine aspartate, L-carnitine citrate,
L-carnitine acid citrate, L-carnitine acid fumarate, L-carnitine
glycerophosphate, L-carnitine mucate, L-carnitine orotate,
L-carnitine oxalate, L-carnitine sulfate, L-carnitine
trichloroacetate, L-carnitine trifluoroacetate, L-carnitine
methanesulfonate, L-carnitine pamoate, and L-carnitine acid
pamoate.
[0016] Suitable alkanoyl L-carnitines include C.sub.2-8 alkanoyl
L-carnitines, particularly acetyl, butyryl, isobutyryl, valeryl,
isovaleryl and more particularly propionyl L-carnitine.
[0017] Suitable salts of alkanoyl L-carnitines include C.sub.2-8
alkanoyl L-carnitine chloride, C.sub.2-8 alkanoyl L-carnitine
bromide, C.sub.2-8 alkanoyl L-carnitine orotate, C.sub.2-8 alkanoyl
L-carnitine acid aspartate, C.sub.2-8 alkanoyl L-carnitine acid
phosphate, C.sub.2-8 alkanoyl L-carnitine fumarate, C.sub.2-8
alkanoyl L-carnitine lactate, C.sub.2-8 alkanoyl L-carnitine
maleate, C.sub.2-8 alkanoyl L-carnitine acid maleate, C.sub.2-8
alkanoyl L-carnitine acid oxalate, C.sub.2-8 alkanoyl L-carnitine
acid sulfate, C.sub.2-8 alkanoyl L-carnitine glucose phosphate,
C.sub.2-8 alkanoyl L-carnitine tartrate, C.sub.2-8 alkanoyl
L-carnitine acid tartrate, C.sub.2-8 alkanoyl L-carnitine iodate,
C.sub.2-8 alkanoyl L-carnitine aspartate, C.sub.2-8 alkanoyl
L-carnitine citrate, C.sub.2-8 alkanoyl L-carnitine acid citrate,
C.sub.2-8 alkanoyl L-carnitine acid fumarate, C.sub.2-8 alkanoyl
L-carnitine glycerophosphate, C.sub.2-8 alkanoyl L-carnitine
mucate, C.sub.2-8, alkanoyl L-carnitine orotate, C.sub.2-8 alkanoyl
L-carnitine oxalate, C.sub.2-8 alkanoyl L-carnitine sulfate,
C.sub.2-8 alkanoyl L-carnitine trichloroacetate, C.sub.2-8 alkanoyl
L-carnitine trifluoroacetate, C.sub.2-8 alkanoyl L-carnitine
methanesulfonate, C.sub.2-8 alkanoyl L-carnitine pamoate, and
C.sub.2-8 alkanoyl L-carnitine acid pamoate.
[0018] Thus, the present invention provides ultra-fine particles of
L-carnitine, as well as ultra-fine particles of a salt of
L-carnitine. The present invention also provides mixtures of
ultra-fine particles of L-carnitine and ultra-fine particles of one
or more salts of L-carnitine, as well as mixtures of ultra-fine
particles of two or more salts of L-carnitine.
[0019] The ultra-fine L-carnitine and salts thereof of the present
invention has a particle sufficiently small that substantially all
of it passes through a 100 United State Bureau of Standards (USBS)
mesh screen. In a preferred embodiment, the ultra-fine L-carnitine
and salts thereof of the present invention has a particle
sufficiently small that substantially all of it passes through a
150 USBS mesh screen. In a particularly preferred embodiment, the
ultra-fine L-carnitine and salts thereof of the present invention
has a particle sufficiently small that substantially all of it
passes through a 200 USBS mesh screen.
[0020] The ultra-fine L-carnitine and salts thereof of the present
invention may be prepared by reducing the size of conventional
L-carnitine and salts thereof and selecting the appropriately sized
particles by sieving. Currently, L-carnitine and salts thereof are
conveniently prepared by the methods described in U.S. Pat. Nos.
4,254,053; 4,602,039; and 5,412,113 and European Patent Application
EP-A-0150688, which are incorporated herein by reference. Such
procedures typically yield L-carnitine having a size of such that
greater than 10% by weight of the L-carnitine is retained by a 50
mesh sieve and more than 40% by weight is retained by a 100 mesh
sieve. The present ultra-fine L-carnitine may be produced by
subjecting such L-carnitine to size reduction. The size reduction
may be carried out by any suitable technique, such as grinding,
milling, etc. Methods of size reduction are well known and are
described in Kirk-Othmer, Encyclopedia of Chemical Technology,
4.sup.th Ed., Wiley, New York, vol. 22, pp. 279-296, 1999, which is
incorporated herein by reference.
[0021] After the conventionally prepared L-carnitine has been
subjected to size reduction, the ultra-fine 1-carnitine of the
present invention may be selected by subjecting the size-reduced
L-carnitine to sieving. Sieving is a well known technique for
selecting materials of a particular size and is described in
Kirk-Othmer, Encyclopedia of Chemical Technology, 4.sup.th Ed.,
Wiley, New York, vol. 22, pp. 256-278, 1999, which is incorporated
herein by reference. The ultra-fine L-carnitine of the present
invention is obtained by selecting that material which passes
through a 100 USBS mesh sieve, preferably a 150 USBS mesh sieve,
more preferably a 200 mesh USBS mesh sieve.
[0022] In another embodiment, the present invention provides
compositions which contain the ultra-fine L-carnitine and a
pharmaceutically acceptable excipient or carrier. Suitable
pharmaceutically acceptable excipients or carriers are described in
Remington's Pharmaceutical Sciences Handbook, Mack Publishing,
which is incorporated herein by reference.
[0023] In a preferred embodiment, the pharmaceutically acceptable
excipient or carrier is an oil-based material, such as synthetic or
natural oil based vitamins including, but not limited to vitamin E,
oils extracted from any seed or vegetable such as, but not limited
to soy, olive, palm, or corn oil, and any nutritive substance that
maybe previously dissolved suspended or mixed in one or more of
such oils.
[0024] The present compositions will suitably contain the
ultra-fine L-carnitine in an amount of 10 to 99% by weight,
preferably 25 to 95% by weight, more preferably 50 to 90% by
weight, based on the total weight of the composition. The present
composition may take the form of soft gelatin capsules, powders,
pills, tablets, etc. In a preferred embodiment, the present
composition is in the form of a gelatin capsule, pre-mix, sachet or
reconstitutable sports drink mix.
[0025] The present composition may further comprise any of the
additional active ingredients which L-carnitine or salts thereof
are known to be combined with, e.g., hydroxycitric acid, Co-enzyme
Q10, chromium picolinate, gamma linolenic acid, resveratrol, omega
3 acids, antioxidants, vitamins, etc.
[0026] In another embodiment, the present invention provides
methods of treatment, therapy, and prevention involving orally
administering to a subject in need of such treatment, therapy, or
prevention, an effective amount of the ultra-fine L-carnitine or
salt thereof of the present invention. Methods of treatment,
therapy, and/or prevention in which the ultra-fine L-carnitine of
the present invention may be used are described in U.S. Pat. Nos.
4,474,812 and 5,861,434, which are incorporated herein by
reference.
[0027] The compound of the invention will have a minimum active
principle of 57%, and still be capable of extended shelf life in
combination formulations contained within soft gelatin capsules,
pre-mixes, sachets and reconstitutable sports drink mixes. A
transformer (a person or entity which will transform the present
ultrafine L-carnitine into a finished product) will succeed in
planned remote geographic markets for dry products that may be
shipped and warehoused economically, then reconstituted locally,
realizing a cost savings and increased opportunity for
customers.
[0028] There are also peripheral benefits since the present
ultra-fine L-carnitine and salts thereof are probably the best
L-Camitine source for combination formulations such as L-Carnitine
and Co-enzyme Q10, due the similarity of particle sizes.
[0029] Ultra-fine L-carnitine fumarate and therefore the compound
of the present invention has been shown to demonstrate an increased
bioavailability through the mitochondrial pathway. This effect is
substantiated with studies that show human plasma levels to equal
those of conventionally sized L-carnitine tartrate for identical
prior dosing. Transformers may therefore accomplish the target
dosage using a reduced active bolus, an efficiency which translates
to cost savings. In principle, consumers purchase nutritionals on a
pure weight/volume (W/V) basis. The marketer who adds more active
weight is judged as having a higher quality product.
[0030] The compound of the invention may be certified "BSE Safe,"
since it contains no animal products and is based upon chemical
synthesis. Avoidance of potential health risks and unnecessary
consumption of unknown organisms, since tartrate is a bioferm.
"International Food Marketing," GreenPeace and others have
published articles on the future risk of BSE. The buying public has
a heightened awareness to this risk.
[0031] The compound of the present invention requires no reworking
(regranulation, conditioning) as tartrate does. Lowered production
costs, labor, environmental exposure. If transformer is not
reworking tartrate, they should, since tablets made with tartrate
as is will not hold up well in gelatine capsules or on shelves.
[0032] The fine particle size (200 Mesh) and coating of hydrophilic
and or hydrophobic silicas provides excellent mixing and content
uniformity properties especially for formulations that use other
finely particled ingredients such as chromium picolinate and
Co-enzyme Q10, as well as extended shelf life due to its inherently
low hygroscopicity. Tooling (punches) and presses theoretically run
cooler, than with tartrate, due to increased lubricity offered by
the silica, which will save expensive downtime thereby reducing
costs.
[0033] The present ultra-fine L-carnitine is particularly useful as
a dietary supplement to ensure a healthy and balanced diet. It is
also useful as a cofactor for weight control and as a dietary
supplement for sport nutrition, vegetarian nutrition, animal
nutrition. It is also useful in veterinary nutrition.
[0034] Other features of the invention will become apparent in the
course of the following descriptions of exemplary embodiments which
are given for illustration of the invention and are not intended to
be limiting thereof.
EXAMPLES
[0035] In the following examples, and throughout this
specification, all parts and percentages are by weight, and all
temperatures are in degrees Celsius, unless expressly stated to be
otherwise. Where the solids content of a dispersion or solution is
reported, it expresses the weight of solids based on the total
weight of the dispersion or solution, respectively. Where a
molecular weight is specified, it is the molecular weight range
ascribed to the product by the commercial supplier, which is
identified. Generally this is believed to be weight average
molecular weight.
Example 1
[0036] L-carnitine fumarate is milled to an over all particle size
so as to minimally pass a number 100 USBS Mesh screen. Particles
utilized to evaluate the efficacy of the invention to date have
actually been milled to pass 150-200 Mesh with outstanding results.
Particles are then blended with a food grade hydrophilic and/or
hydrophobic fumed or precipitated silica(s) of the type available
from Degussa, Inc. that poses an overall surface area of 190-475
square meters per gram and a tapped density of 80-275 grams per
liter.
[0037] Ultra-fine L-carnitine fumarate so prepared has the
following analytical properties:
1 Description: white crystalline powder Assay: 58.0% .+-. 2%
carnitine 41.5% .+-. 1% fumaric acid Water content: .ltoreq.1%
(Karl Fischer) Specific rotation: [.alpha.].sub.D.sup.20 =
17.5.degree. .+-. 1.degree. (1% in water) pH: 3.0 to 4.0 (1% in
water) Solubility: 5 g/100 ml in water Mesh size: Passes 150 mesh
conditioned with fumed food grade silica Toxicity: LD.sub.50 (oral)
> 8,000 mg/kg (rats)
[0038] Obviously, numerous modifications and variations of the
present invention are possible in light of the above teachings. It
is therefore to be understood that, within the scope of the
appended claims, the invention may be practiced otherwise than as
specifically described herein.
[0039] All patents and other references mentioned above are
incorporated in full herein by this reference, the same as if set
forth at length.
[0040] This application is based on U.S. Provisional Application
No. 60/152,240 filed on Sep. 3, 1999, and U.S. Provisional
Application No. 60/158,245 filed on Oct. 8, 1999, both of which are
incorporated herein by reference in their entirety.
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