U.S. patent application number 10/721373 was filed with the patent office on 2004-07-08 for liposomal analgesic formulation and use.
This patent application is currently assigned to IDEXX Laboratories, Inc.. Invention is credited to Hepler, Douglas I., Lynn, Randy Carl.
Application Number | 20040131667 10/721373 |
Document ID | / |
Family ID | 32594293 |
Filed Date | 2004-07-08 |
United States Patent
Application |
20040131667 |
Kind Code |
A1 |
Hepler, Douglas I. ; et
al. |
July 8, 2004 |
Liposomal analgesic formulation and use
Abstract
The invention provides methods and compositions for the
treatment of lameness, navicular syndrome, osteoarthritis, or
combinations thereof in horses.
Inventors: |
Hepler, Douglas I.;
(McLeansville, NC) ; Lynn, Randy Carl;
(Greensboro, NC) |
Correspondence
Address: |
Patrick G. Gattari
McDonnell Boehnen Hulbert & Berghoff
32nd Floor
300 S. Wacker Drive
Chicago
IL
60606
US
|
Assignee: |
IDEXX Laboratories, Inc.
Westbrook
ME
|
Family ID: |
32594293 |
Appl. No.: |
10/721373 |
Filed: |
November 25, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10721373 |
Nov 25, 2003 |
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10327575 |
Dec 20, 2002 |
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Current U.S.
Class: |
424/450 ;
514/458; 514/567; 514/78 |
Current CPC
Class: |
A61K 9/0017 20130101;
A61K 9/127 20130101; A61K 31/685 20130101; A61K 31/196 20130101;
A61K 31/195 20130101; A61K 45/06 20130101; A61K 31/355 20130101;
A61K 31/195 20130101; A61K 2300/00 20130101; A61K 31/196 20130101;
A61K 2300/00 20130101; A61K 31/355 20130101; A61K 2300/00 20130101;
A61K 31/685 20130101; A61K 2300/00 20130101 |
Class at
Publication: |
424/450 ;
514/078; 514/567; 514/458 |
International
Class: |
A61K 031/685; A61K
009/127; A61K 031/355; A61K 031/195 |
Claims
What is claimed is:
1. A method for treating lameness in a horse comprising topically
administering to the horse a formulation comprising: (a) about 0.1%
to about 5% diclofenac; and (b) about 0.5% to about 20%
phospholipids; whereby lameness in the horse is treated.
2. The method of claim 1, wherein the formulation further comprises
about 0.1% to about 10% vitamin E.
3. The method of claim 1, wherein the formulation further comprises
about 1% to about 20% alkylane glycol; and about 1% to about 50%
(C.sub.1-C.sub.6) alcohol.
3. The method of claim 1, wherein the formulation comprises: (a)
about 1% diclofenac salt, (b) about 5% propylene glycol, (c) about
6% ethanol, (d) about 1% vitamin E acetate, (e) about 10%
phospholipid, and (f) about 77% water.
4. The method of claim 1, wherein the formulation comprises about 2
to about 10 micron liposomes.
5. The method of claim 1, wherein the formulation is topically
administered twice daily.
6. The method of claim 1, wherein about 20 mg to about 120 mg of
diclofenac is applied as a single dose to the horse.
7. The method of claim 1, wherein about 70 mg to about 80 mg of
diclofenac is applied as a single dose to the horse.
8. The method of claim 5, wherein two doses per day are applied to
the horse for at least about three days.
9. The method of claim 2, wherein the vitamin E is a
C.sub.2-C.sub.6 ester of vitamin E.
10. The method of claim 2, wherein the vitamin E is vitamin E
acetate.
11. The method claim 1, wherein the diclofenac is a diclofenac
salt.
12. The method of claim 3, wherein the alkylane glycol is propylene
glycol.
13. The method of claim 3, wherein the C.sub.1-C.sub.6 alcohol is
ethanol.
14. A method for treating osteoarthritis in a horse comprising
topically administering to a horse a formulation comprising: (a)
about 1% to about 5% diclofenac; and (b) about 0.5% to about 20%
phospholipids; whereby osteoarthritis in the horse is treated.
15. The method of claim 14, wherein the formulation further
comprises about 0.1% to about 10% vitamin E.
16. The method of claim 14, wherein the formulation further
comprises about 1% to about 20% alkylane glycol; and about 1% to
about 50% (C.sub.1-C.sub.6) alcohol.
17. The method of claim 14, wherein the formulation comprises: (a)
about 1% diclofenac salt, (b) about 5% propylene glycol, (c) about
6% ethanol, (d) about 1% vitamin E acetate, (e) about 10%
phospholipid, and (g) about 77% water.
18. The method of claim 14, wherein the formulation comprises about
2 to about 10 micron liposomes.
19. The method of claim 14, wherein the formulation is topically
administered twice daily.
20. The method of claim 14, wherein about 20 mg to about 120 mg of
diclofenac is applied as a single dose to the horse.
21. The method of claim 14, wherein about 70 mg to about 80 mg of
diclofenac is applied as a single dose to the horse.
22. The method of claim 19, wherein two doses per day are applied
to the horse for at least about three days.
23. The method of claim 15, wherein the vitamin E is a
C.sub.2-C.sub.6 ester of vitamin E.
24. The method of claim 15, wherein the vitamin E is vitamin E
acetate.
25. The method claim 14, wherein the diclofenac is a diclofenac
salt.
26. The method of claim 16, wherein the alkylane glycol is
propylene glycol.
27. The method of claim 16, wherein the C.sub.1-C.sub.6 alcohol is
ethanol.
28. A method for treating navicular syndrome in a horse comprising
topically administering to the a horse a formulation comprising:
(a) about 0.1% to about 5% diclofenac; and (b) about 0.5% to about
20% phospholipids; whereby navicular syndrome in the horse is
treated.
29. The method of claim 28, wherein the formulation further
comprises about 0.1% to about 10% vitamin E.
30. The method of claim 28, wherein the formulation further
comprises about 1% to about 20% alkylane glycol; and about 1% to
about 50% (C.sub.1-C.sub.6) alcohol.
31. The method of claim 28, wherein the formulation comprises: (a)
about 1% diclofenac salt, (b) about 5% propylene glycol, (c) about
6% ethanol, (d) about 1% vitamin E acetate, (e) about 10%
phospholipid, and (h) about 77% water.
32. The method of claim 28, wherein the formulation comprises about
2 to about 10 micron liposomes.
33. The method of claim 28, wherein the formulation is topically
administered twice daily.
34. The method of claim 28, wherein about 20 mg to about 120 mg of
diclofenac is applied as a single dose to the horse.
35. The method of claim 28, wherein about 70 mg to about 80 mg of
diclofenac is applied as a single dose to the horse.
36. The method of claim 33, wherein two doses per day are applied
to the horse for at least about three days.
37. The method of claim 29, wherein the vitamin E is a
C.sub.2-C.sub.6 ester of vitamin E.
38. The method of claim 29, wherein the vitamin E is vitamin E
acetate.
39. The method claim 28, wherein the diclofenac is a diclofenac
salt.
40. The method of claim 30, wherein the alkylane glycol is
propylene glycol.
41. The method of claim 30, wherein the C.sub.1-C.sub.6 alcohol is
ethanol.
Description
PRIORITY INFORMATION
[0001] This application is a continuation in part of U.S.
application Ser. No. 10/327,575, filed Dec. 20, 2002, which is
incorporated herein in its entirety.
FIELD OF THE INVENTION
[0002] This invention is in the field of liposomal non-steroidal
anti-inflammatory formulations.
SUMMARY OF THE INVENTION
[0003] One embodiment of the invention provides a method for
treating lameness, navicular syndrome, osteoarthritis or a
combination thereof in a horse. The method comprises topically
administering to the a horse a formulation comprising: about 0.1%
to about 5% diclofenac and about 0.5% to about 20% phospholipids,
whereby lameness, navicular syndrome, osteoarthritis or a
combination thereof in the horse is treated. The formulation can
further comprise about 0.1% to about 10% vitamin E. The formulation
can further comprise about 1% to about 20% alkylane glycol, and
about 1% to about 50% (C.sub.1-C.sub.6) alcohol. The formulation
can comprise about 1% diclofenac salt, about 5% propylene glycol,
about 6% ethanol, about 1% vitamin E acetate, about 10%
phospholipid, and about 77% water. The formulation can comprise
about 2 to about 10 micron liposomes. The formulation can be
topically administered twice daily. About 20 mg to about 120 mg of
diclofenac can be applied as a single dose to the horse. About 70
mg to about 80 mg of diclofenac can be applied as a single dose to
the horse. Two doses per day can be applied to the horse for at
least about three days. The vitamin E can be a C.sub.2-C.sub.6
ester of vitamin E. The vitamin E can be vitamin E acetate. The
diclofenac can be a diclofenac salt. The alkylane glycol can be
propylene glycol. The C.sub.1-C.sub.6 alcohol can be ethanol.
DETAILED DESCRIPTION OF THE INVENTION
[0004] It has been discovered that a liposome formulation
containing about 0.1% to about 5% diclofenac is an effective
topical anti-inflammatory treatment for lameness, navicular
syndrome, osteoarthritis, or a combination thereof in horses. More
particularly it has been discovered that a formulation containing,
for example, vitamin E, phospholipid and diclofenac salt such as
the sodium or potassium salt is a highly effective topical
anti-inflammatory formulation that is particularly effective in
treating lameness in horses.
[0005] Compositions
[0006] A formulation refers to a composition in a form suitable for
topical administration to a subject. A subject can be a member of
the Equidae family, for example, a horse.
[0007] A formulation of the invention comprises about 0.1% to about
5% diclofenac. All percentages are based on total weight of the
formulation. Diclofenac is described in U.S. Pat. No. 3,558,690 and
in Merck Index 3071 eleventh Edition. Various diclofenac products
are described in Physicians Desk Reference. In one embodiment, a
formulation of the invention comprises about 0.7 to about 1.3%
diclofenac, and in another embodiment, a formulation comprises
about 1% diclofenac. Diclofenac can be a salt of diclofenac such as
diclofenac sodium salt, diclofenac potassium salt, diclofenac
diethylammonium salt, diclofenac hydroxyethylpyrrolidine salt,
diclofenac diethylamine salt, diclofenac rubidium salt, diclofenac
caesium salt, or diclofenac calcium salt.
[0008] A formulation of the invention can comprise about 0.1% to
about 10% vitamin E. In one embodiment of the invention, vitamin E
comprises about 0.5 to about 1.5% of a formulation, in another
embodiment of the invention the formulation comprises about 1%
vitamin E. Vitamin E can be a C.sub.2-C.sub.6 ester of vitamin E,
for example, vitamin E acetate.
[0009] A formulation of the invention can comprise about 0.5 to
about 20% phospholipids. In another embodiment of the invention,
the formulation can comprise about 5% to about 15% phospholipids.
In one embodiment of the invention, a formulation. can comprise
about 10% phospholipids. Any phospholipid suitable for topical
administration can be used in a formulation of the invention. See
e.g., Gennaro, Remington: The Science and Practice of Pharmacy,
(June 2003), Lippincott Williams & Wilkins Publishers,
Philadelphia, Pa.; Ansel et al., Pharmaceutical Dosage Forms and
Drug Delivery Systems, 7th edition (July 2004), Lippincott Williams
& Wilkins Publishers, Philadelphia, Pa.; U.S. Pat. No.
4,937,078.
[0010] In one embodiment of the invention a phospholipid is
phospholipon 90H HYD Lechthin (Aventis, Bridgewater Crossings,
N.J., USA ). Other useful lipids are obtainable from a number of
sources. Natural phosphatide mixtures from egg or soy containing
more than 70% phosphatidylcholine are obtained from a number of
commercial sources such as Sigma Chemical of St. Louis, Mo., and
Lipoid KG, Ludwigshafen, West Ger., Hepar of Franklin, Ohio. Hepar
supplies egg phosphatidylcholine. Other sources of lipid such as
soy phosphatidylcholine are American Lecithin, Woodside, L.I.,
N.Y., and Riceland Foods, Little Rock, Ark. Phosphatidic acid of
99% purity is obtained from Avanti Chemical of Birmingham, Ala.
Purified natural soybean lecithin having about 80%
phosphotidylcholine 2% lysophosphatidylcholine, 4% phosphatic acid
and about 1% monophosphatidyllinosilol are also suitable for
practicing the invention. Those skilled in the art will recognize a
variety of suitable phospholipid compositions useful in the present
invention. For example, U.S. Pat. No. 5,154,930 describes the use
of liposomes in the delivery of diclofenac. U.S. Pat. No. 5,738,869
describes a phospholipid transdermal drug delivery system
containing .alpha.-tocopherol, aliphatic alcohol and dicblfenac.
U.S. Pat. No. 4,761,288 discloses the use of multilamellar lipid
vesicles having a saturated solution and solid form of a drug
captured therein. U.S. Pat. No. 4,897,269 relates to topical
administration of drugs using drugs captured in lipid vesicles.
U.S. Pat. No. 6,423,338 describes phospholipids containing
microcrystals of drugs.
[0011] In one embodiment of the invention, the phospholipids form
liposomes or vesicles of, for example, about 1 to about 30 microns,
more preferably from about 2 to about 10 microns
[0012] A formulation of the invention can comprise about 1% to
about 20% alkylane glycol, in another embodiment a formulation can
comprise about 3% to about 7% alkylane glycol, and in another
embodiment of the invention a formulation can comprise about 5%
alkylane glycol. Any alkylane glycol suitable for topical
administration can be used in the invention. See e.g., Gennaro,
Remington: The Science and Practice of Pharmacy; Ansel et al.,
Pharmaceutical Dosage Forms and Drug Delivery Systems. In one
embodiment of the invention an alkylane glycol is propylene
glycol.
[0013] A formulation of the invention can comprise about 1% to
about 50% (C.sub.1-C.sub.6) alcohol, in another embodiment a
formulation can comprise about 3% to about 9% (C.sub.1-C.sub.6)
alcohol, and in another embodiment of the invention a formulation
can comprise about 6% (C.sub.1-C.sub.6) alcohol. Any alkylane
glycol suitable for topical administration can be used in the
invention. See e.g., Gennaro, Remington: The Science and Practice
of Pharmacy; Ansel et al., Pharmaceutical Dosage Formns and Drug
Delivery Systems. In one embodiment of the invention an alkylane
glycol is propylene glycol.
[0014] Formulations of the invention can comprise about 99% to
about 30% water, excipients, or other minor ingredients (i.e.
preservatives, perfumes, colorants and the like). In one embodiment
of the invention, a formulation comprises about 90%, about 80%,
about 77%, about 70%, about 60%, about 50%, about 40%, or about 30%
water. Excipients and minor ingredients suitable for the
formulations of the invention are described in, for example,
Gennaro, Remington: The Science and Practice of Pharmacy; Ansel et
al., Pharmaceutical Dosage Forms and Drug Delivery Systems.
[0015] One embodiment of the invention provides a formulation that
comprises about 1% vitamin E acetate, about 10% phospholipid, about
1% diclofenac, about 5% propylene glycol, about 6% ethanol and
about 77% water. The formulation can comprise about 2 to about 10
micron lipid vesicles or liposomes that contain diclofenac. The
composition can also contain small amounts of benzethonium chloride
or other preservative.
[0016] One embodiment of the invention provides a formulation
having about 0.5% to about 1.5% of Vitamin E ester, about 5% to
about 15% of phospholipid, about 0.7% to about 1.3% diclofenac,
about 3% to about 7% alkylane glycol, about 3% to about 9% of
(C.sub.1-C.sub.6) alcohol and the remainder water or other minor
ingredients (i.e. preservatives, perfumes, colorants and the
like).
[0017] One embodiment of the invention provides a formulation
comprising about 0.5% to about 1.5% of vitamin E, or a
C.sub.2-C.sub.6 ester of vitamin E; about 5% to about15%
phospholipid; about 3 to about 7% alkylane glycol comprising about
2-5 carbon atoms, preferably propylene glycol; about 3% to about 9%
of (C.sub.1-C.sub.6) alcohol, preferably ethanol; about 0.7% to
about 1.3% diclofenac, preferably about 1%; and the remainder
water, wherein the formulation contains about 2 to about 10 micron
lipid vesicles.
[0018] Methods of Treatment
[0019] Formulations of the invention can be used to treat members
of the Equidae family, including, for example, horses. Treatment
means the elimination or reduction of one or more symptoms of
lameness, osteoarthritis, navicular syndrome, or combinations
thereof.
[0020] Lameness is an irregular gait caused by perception of a pain
by partially or fully bearing weight on one or more legs. Lameness
can be intermittent or continuous for a period of days, weeks or
months.
[0021] Lameness can result from, for example, painful lesions on
bone structure, cartilage, ligaments, the synovial membrane or
connective tissue; from a change in bone architecture and/or in the
bone growth cartilages at the site of lameness, such as, losses of
bone substance, the formation of cysts, deformation of the bone or
excessive thickening of the growth cartilages; from a change in the
structure of the articular cartilages, such as, for example,
erosions of the cartilaginous surfaces and/or a change in the
synovial membrane and/or a change in the articular ligaments; from
an anomaly of local vascularization, for example, a reduction in
vascularization; from a change in muscle development, such as
muscular atrophy, or a combination thereof.
[0022] Navicular syndrome is one of several conditions leading to
heel soreness or lameness. Navicular syndrome is usually a chronic
bilateral foreleg lameness. Horses with navicular syndrome can have
a choppy, shuffling type gait and can wear the toes of their feet
leaving the heels to grow longer. Horses with an upright
conformation, small feet, or that are improperly shod can be at
higher risk for the syndrome since they transmit more concussive
force through the navicular region. The more pressure that is
applied to the navicular bone from the deep flexor tendon, the more
likely the horse will suffer from navicular disease. This
repetitive force can result in damage and inflammation to the
navicular bone resulting in navicular syndrome. Diagnosis of
navicular syndrome is based on a clinical examination
(characteristic gait, hoof tester response, specific nerve blocks,
and palpation) and radiographic evaluation.
[0023] Osteoarthritis is a degenerative joint disease. The
condition is characterized by degeneration of the articular
cartilage, hypertrophy of bone at the margins and changes in the
synovial membrane. Osteoarthritis primarily affects weight-bearing
joints in horses such as the hocks (ankles) where it can be
referred to as bone spavins, fetlocks, pastern joints and coffin
joints, where it is referred to as ringbone when more severe, knee
joints, spine (neck and back). Osteoarthritis can affect other
joints especially where previous injury has occurred or areas where
there has been repetitive or abnormal stress. Osteoarthritis can
result from injury, loose joints, an abnormal growth pattern, or
inherited factors.
[0024] Administration
[0025] A formulation of the invention is topically administered to
a subject. Topical administration means directly layering, applying
or spreading upon epidermal tissue, especially outer skin or
membrane, including the hoof. A formulation is applied to or near
the affected area of the subject, for example to the area of a
joint affected by lameness. The formulation can be administered to
any affected area of the subject.
[0026] A three to seven inch ribbon, preferably about a five inch
ribbon, of a formulation is generally applied once or twice daily
for about 3 to about 10 days. This equates to between about 20 mg
to about 120 mg diclofenac, preferably between about 70 mg to about
80 mg per dose (i.e., per application). Other dosages can be used,
such as those disclosed in U.S. Pat. No. 4,937,078. A formulation
can also be administered as one, two, three or more doses per day.
Administration can continue for anywhere between 1 and 30 days or
longer.
[0027] The following examples are intended to illustrate but not
limit the invention. While they are typical of those that might be
used, other procedures known to those of ordinary skill in the art
may alternatively be used.
[0028] All patents and publications mentioned in the specification
are indicative of the levels of skill of those skilled in the art
to which the invention pertains. All references cited in this
disclosure are incorporated by reference to the same extent as if
each reference had been incorporated by reference in its entirety
individually.
[0029] The methods and compositions described herein as presently
representative of preferred embodiments are exemplary and are not
intended as limitations on the scope of the invention. Changes
therein and other uses will occur to those skilled in the art,
which are encompassed within the spirit of the invention, are
defined by the scope of the claims.
[0030] The invention illustratively described herein suitably can
be practiced in the absence of any element or elements, limitation
or limitations that are not specifically disclosed herein. Thus,
for example, in each instance herein any of the terms "comprising",
"consisting essentially of", and "consisting of" may be replaced
with either of the other two terms. The terms and expressions which
have been employed are used as terms of description and not of
limitation, and there is no intention that in the use of such terms
and expressions of excluding any equivalents of the features shown
and described or portions thereof, but it is recognized that
various modifications are possible within the scope of the
invention claimed. Thus, it should be understood that although the
present invention has been specifically disclosed by preferred
embodiments, optional features, modification and variation of the
concepts herein disclosed may be resorted to by those skilled in
the art, and that such modifications and variations are considered
to be within the scope of this invention as defined by the
description and the appended claims.
[0031] In addition, where features or aspects of the invention are
described in terms of Markush groups or other grouping of
alternatives, those skilled in the art will recognize that the
invention is also thereby described in terms of any individual
member or subgroup of members of the Markush group or other
group.
EXAMPLES
Example 1
Formulation Preparation
[0032] To a 600 gallon jacketed stainless steel kettle equipped
with a primary scraper and a secondary mixer is added 396 grams of
benzethonium chloride in about 602 grams of purified water at a
temperature of 550 to 65.degree. C. The benzethonium chloride
container is rinsed with an addition of 602 grams of water. To the
solution in the kettle is added 118.8 kg of ethanol and 99.0 kg of
propylene glycol.
[0033] 19.8 kg of vitamin E acetate, 200.6 kg of phospholipon 90H
HYD lecithin, and 19.8 kg of diclofenac sodium is added in sequence
to an auxiliary tank at 55.degree. C. to 65.degree. C. and mixed
for about 15 minutes. The auxiliary tank is weighed and evaporated
alcohol is replaced. The material in the auxiliary tank is passed
into the manufacturing kettle at a rate of 3 to 5 kg/minute and the
auxiliary tank is rinsed twice with 13.2 kg of water at 55.degree.
C. to 65.degree. C. The bulk material in the manufacturing kettle
is passed through a 60 mesh screen during circulation. The
circulation rate is about 95 kg to 105 kg per minute.
[0034] The vessel bulk mixture is stirred and cooled to 30.degree.
C. and after cooling for about 45 minutes a sample is removed and
tested for temperature and mean volume vesicle particle size. When
the temperature is about 32.degree. C. and the liposome vesicle
particle size is between about 2 and 10 microns agitation is
stopped.
Example 2
Clinical Study-Osteoarthritis
[0035] A clinical study was performed in horses with osteoarthritis
utilizing the 1% of diclofenac formulation described in Example 1.
Lameness was graded using the AAEP (American Association of Equine
Practitioners) lameness scale. Pain, joint mobility and lameness
were also evaluated. The clinical investigator was completely
masked to study treatment. Each tube of test article was identified
only by study case number. The study was conducted for five days.
During the study, between about 20 to 114 mg diclofenac were
applied twice daily. On average, each dose was achieved by applying
a five-inch ribbon of suspension (approximately 73 mg diclofenac
per dose).
[0036] The study was performed on 116 horses in eight states. The
test article had a significant positive effect on lameness, pain
and owner's evaluation of lameness. There was no significant effect
on joint mobility in this study.
[0037] Results
1 Parameter Placebo Diclofenac Comments Lameness .DELTA.L (S.D.)
-0.02 (1.12) -1.48 (1.07) p < 0.0001 Lameness Improved 17/56
(30%) 46/60 (77%) p < 0.0001 Pain .DELTA.P (S.D.) 0.00 (0.91)
-0.48 (0.68) p = 0.0025 Pain Improved 15/56 (27%) 23/60 (38%) p =
0.1299 Mobility Improved 9/56 (16%) 15/60 (25%) p = 0.1694 Owner
Improved 21/56 (38%) 47/59 (80%) p < 0.0001
[0038] Of the 60 horses that received the test article, no adverse
reactions were attributable to topical administration of
diclofenac.
[0039] This study showed that the presently disclosed 1% diclofenac
liposomal suspension, applied twice daily was effective in
improving three of the four study parameters. Statistically, the
effect was highly significant.
[0040] Pivotal target animal safety studies were conducted with
treatment doses of 0.6, 1.7, 2.8 and 5.6 times the effective dose
of 73 mg twice daily. There were no toxic reactions observed, based
upon physical examination, CBC, serum biochemistry, gastroscopy
gross necropsy and histopathology. These data support the safety of
doses above 73 mg twice daily and treatment duration of 10
days.
[0041] A preparation containing 2% diclofenac processed in a
similar manner did not contain phospholipid vesicles and was not
effective.
Example 3
Clinical Study-Navicular Syndrome
[0042] Exploratory clinical studies were conducted by veterinarians
in California, Colorado and Kentucky. Each veterinarian identified
horses with chronic navicular syndrome. Each veterinarian applied a
five-inch ribbon of 1% of diclofenac formulation described in
Example 1 twice daily for 10 days. The formulation was applied to
the coronary band and bulbs of the heals. Approximately 10 horses
were treated. In this study, the veterinarians judged all the
treated horses were improved after treatment with the diclofenac
suspension. The horses retained that improvement for approximately
seven (7) days after the application was discontinued.
* * * * *