U.S. patent application number 10/365082 was filed with the patent office on 2003-08-21 for method for treating a non-rhinorrhea cholinergic influenced secretion.
Invention is credited to Aoki, Kei Roger, Grayston, Michael W..
Application Number | 20030157134 10/365082 |
Document ID | / |
Family ID | 27390366 |
Filed Date | 2003-08-21 |
United States Patent
Application |
20030157134 |
Kind Code |
A1 |
Aoki, Kei Roger ; et
al. |
August 21, 2003 |
Method for treating a non-rhinorrhea cholinergic influenced
secretion
Abstract
A method and composition for treating a patient suffering from
an excessive glandular secretion includes administration to the
patient of a therapeutically effective amount of a botulinum toxin
type A, B, C, D, E, F and/or G.
Inventors: |
Aoki, Kei Roger; (Coto de
caza, CA) ; Grayston, Michael W.; (Irvine,
CA) |
Correspondence
Address: |
Stephen Donovan
Allergan, Inc.
2525 Dupont Drive, T2-7H
Irvine
CA
92612
US
|
Family ID: |
27390366 |
Appl. No.: |
10/365082 |
Filed: |
February 11, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10365082 |
Feb 11, 2003 |
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10008722 |
Dec 6, 2001 |
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10008722 |
Dec 6, 2001 |
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09487477 |
Jan 19, 2000 |
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09487477 |
Jan 19, 2000 |
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08627118 |
Apr 3, 1996 |
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08627118 |
Apr 3, 1996 |
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08173996 |
Dec 28, 1993 |
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Current U.S.
Class: |
424/239.1 |
Current CPC
Class: |
A61K 38/4893
20130101 |
Class at
Publication: |
424/239.1 |
International
Class: |
A61K 039/08 |
Claims
What is claimed is:
1. A method for treating an excessively secreting cholinergically
influenced gland, the method comprising the step of injecting an
excessively secreting cholinergically influenced gland, or the
local area of the gland, with a botulinum toxin in order to reduce
an excessive secretory activity of the gland, wherein the secretion
is not a symptom of rhinorrhea.
2. The method of claim 1, wherein the botulinum toxin is botulinum
toxin type A.
3. The method of claim 1, wherein the botulinum toxin is selected
from the group consisting of botulinum toxin types A, B, C, D, E, F
and G.
4. The method of claim 1, wherein the botulinum toxin is
administered in an amount of between 0.01 units and 5000 units.
5. The method of claim 1, wherein the botulinum toxin is
administered in an amount of between 0.01 unit and 500 units.
6. A method for treating an excessively secreting cholinergically
influenced gland, the method comprising the step of injecting an
excessively secreting cholinergically influenced gland, or the
local area of the gland, with a botulinum toxin type A in order to
reduce an excessive secretory activity of the gland, wherein the
secretion is not a symptom of rhinorrhea.
7. A method for treating an excessively secreting gland, the method
comprising the step of injecting an excessively secreting gland, or
the local area of the gland, with a botulinum toxin in order to
reduce an excessive secretory activity of the gland, wherein the
secretion is not a symptom of rhinorrhea.
8. The method of claim 7, wherein the botulinum toxin is selected
from the group consisting of botulinum toxin types A, B, C, D, E, F
and G.
Description
CROSS-REFERENCE
[0001] This application is a continuation of application Ser. No.
10/008,722, filed Dec. 6, 2001, which is a continuation-in-part of
Ser. No. 09/487,477, filed Jan. 19, 2000, which is a divisional of
Ser. No. 08/627,118, filed Apr. 3, 1996, which is a continuation of
Ser No. 08/173,996, filed Dec. 28, 1993, now abandoned. The
contents of these prior filed applications are hereby incorporated
by referenced in their entireties.
FIELD OF THE INVENTION
[0002] The present invention provides novel methods for treating
various disorders and conditions, with a botulinum toxin, including
excessive mucus secretions. Importantly, the present invention
provides methods useful in relieving pain related to muscle
activity or contracture and therefore is of advantage in the
treatment of, for example, muscle spasm such as Temporomandibular
Joint Disease, low back pain, myofascial pain, pain related to
spasticity and dystonia, as well as sports injuries, and pain
related to contractures in arthritis.
BACKGROUND OF THE INVENTION
[0003] Heretofore, Botulinum toxins, in particular Botulinum toxin
type A, has been used in the treatment of a number of neuromuscular
disorders and conditions involving muscular spasm; for example,
strabismus, blepharospasm, spasmodic torticollis (cervical
dystonia), oromandibular dystonia and spasmodic dysphonia
(laryngeal dystonia). The toxin binds rapidly and strongly to
presynaptic cholinergic nerve terminals and inhibits the exocytosis
of acetylcholine by decreasing the frequency of acetylcholine
release. This results in local paralysis and hence relaxation of
the muscle afflicted by spasm.
[0004] For one example of treating neuromuscular disorders, see
U.S. Pat. No. 5,053,005 to Borodic, which suggests treating
curvature of the juvenile spine, i.e., scoliosis, with an
acetylcholine release inhibitor, preferably Botulinum toxin A.
[0005] For the treatment of strabismus with Botulinum toxin type A,
see Elston, J. S., et al., British Journal of Ophthalmology, 1985,
69, 718-724 and 891-896. For the treatment of blepharospasm with
Botulinum toxin type A, see Adenis, J. P., et al., J. Fr.
Ophthalmol, 1990,13 (5) at pages 259-264. For treating squint, see
Elston, J. S., Eye, 1990, 4(4):VII. For treating spasmodic and
oromandibular dystonia torticollis, see Jankovic et al., Neurology,
1987, 37, 616-623.
[0006] Spasmodic dysphonia has been treated with Botulinum toxin
type A. See Blitzer et al., Ann. Otol. Rhino. Latyngol, 1985, 94,
591-594. Lingual dystonia was treated with Botulinum toxin type A
according to Brin et al., Adv. Neurol. (1987) 50, 599-608. Finally,
Cohen et al., Neurology (1987) 37 (Suppl. 1), 123-4, discloses the
treatment of writer's cramp with Botulinum toxin type A.
[0007] The term Botulinum toxin is a generic term embracing the
family of toxins produced by the anaerobic bacterium Clostridium
botulinum and, to date, seven immunologically distinct neurotoxins
have been identified. These have been given the designations A, B,
C, D, E, F and G. For further information concerning the properties
of the various Botulinum toxins, reference is made to the article
by Jankovic and Brin, The New England Journal of Medicine, No. 17,
1990, pp. 1186-1194, and to the review by Charles L. Hatheway in
Chapter 1 of the book entitled Botulinum Neurotoxin and Tetanus
Toxin, L. L. Simpson, Ed., published by Academic Press Inc. of San
Diego, Calif., 1989, the disclosures in which are incorporated
herein by reference.
[0008] The neurotoxic component of Botulinum toxin has a molecular
weight of about 150 kilodaltons and is thought to comprise a short
polypeptide chain of about 50 kD which is considered to be
responsible for the toxic properties of the toxin, i.e., by
interfering with the exocytosis of acetylcholine, by decreasing the
frequency of acetylcholine release, and a larger polypeptide chain
of about 100 kD which is believed to be necessary to enable the
toxin to bind to the presynaptic membrane.
[0009] The "short" and "long" chains are linked together by means
of a simple disulfide bridge. (It is noted that certain serotypes
of Botulinum toxin, e.g., type E, may exist in the form of a single
chain un-nicked protein, as opposed to a dichain. The single chain
form is less active but may be converted to the corresponding
dichain by nicking with a protease, e.g., trypsin. Both the single
and the dichain are useful in the method of the present
invention.)
[0010] In general, four physiologic groups of C. botulinum are
recognized (I, II, III, IV). The organisms capable of producing a
serologically distinct toxin may come from more than one
physiological group. For example, Type B and F toxins can be
produced by strains from Group I or II. In addition, other strains
of clostridial species (C. baratii, type F; C. butyricum, type E;
C. novyi, type C.sub.1 or D) have been identified which can produce
botulinum neurotoxins.
[0011] Immunotoxin conjugates of ricin and antibodies, which are
characterized as having enhanced cytotoxicity through improving
cell surface affinity, are disclosed in European Patent
Specification 0 129 434. The inventors note that botulinum toxin
may be utilized in place of ricin.
[0012] Botulinum toxin is obtained commercially by establishing and
growing cultures of C. botulinum in a fermenter and then harvesting
and purifying the fermented mixture in accordance with known
techniques.
[0013] Botulinum toxin type A, the toxin type generally utilized in
treating neuromuscular conditions, is currently available
commercially from several sources; for example, from Porton
Products Ltd. UK, under the trade name "DYSPORT," and from
Allergan, Inc., Irvine, Calif., under the trade name
BOTOX.RTM..
[0014] It is one object of the invention to provide novel
treatments of neuromuscular disorders and conditions with various
Botulinum toxin types. It is another object of the present
invention to relieve pain with various Botulinum toxin types.
SUMMARY OF THE INVENTION
[0015] The present invention provides a method for relieving pain,
associated with muscle contractions, a composition and a method of
treating conditions such as cholinergic controlled secretions
including excessive sweating, lacrimation and mucus secretions and
a method for treating smooth muscle disorders including, but not
limited to, spasms in the sphincter of the cardiovascular
arteriole, gastrointestinal system, urinary, gall bladder and
rectum, which method comprises administering to the patient
suffering from said disorder or condition a therapeutically
effective amount of Botulinum toxin selected from the group
consisting of Botulinum toxin types B, C, D, E, F and G.
[0016] Each serotype of Botulinum toxin has been identified as
immunologically different proteins through the use of specific
antibodies. For example, if the antibody (antitoxin) recognizes,
that is, neutralizes the biological activity of, for example, type
A it will not recognize types B, C, D, E, For G.
[0017] While all of the Botulinum toxins appear to be zinc
endopeptidases, the mechanism of action of different serotypes, for
example, A and E within the neuron appear to be different than that
of Type B. In addition, the neuronal surface "receptor" for the
toxin appears to be different for the serotypes.
[0018] In the area of use of the Botulinum toxins in accordance
with the present invention with regard to organ systems which
involve the release of neurotransmitter, it is expected to
introduce the toxins A, B, C, D, E, F, and G directly by local
injections.
[0019] The present invention comprises a method for treating a
mucus secretion of a patient by local administration to a patient
an effective amount of a botulinum toxin (A, B, C, D, E, F or G) in
order to reduce a mucus secretion of the patient. The mucus
secretion is not a symptom of rhinorrhea. The mucus secretion can
be a cholinergic influenced mucus secretion. The botulinum toxin
can be administered in an amount of between 0.01 units and 5000
units, such as between 0.01 unit and 500 units.
[0020] A detailed embodiment of the present invention comprises a
method for treating a cholinergic influenced mucus secretion of a
human patient by administering to a human patient a therapeutically
effective amount of botulinum toxin type A in order to reduce the
mucus secretion, wherein the mucus secretion is not a symptom of
rhinorrhea. A further method for treating a mucus secreting gland
can comprise the step of administering to a mucus secreting gland a
botulinum toxin thereby reducing a mucus secretory activity of the
gland, wherein the mucus secretion is not a symptom of rhinorrhea.
The gland can be an excessively secreting mucus gland influenced by
the cholinergic nervous system. The botulinum toxin can be
administered by injection into the mucus gland or into the local
area of the mucus gland.
[0021] Another detailed embodiment of the present invention can
comprise a method for treating an excessively secreting mucus
gland, the method comprising the step of injecting an excessively
secreting, cholinergic nervous system influenced mucus gland or
local mucus gland area of a human patient with a therapeutically
effective amount of botulinum toxin type A in order to reduce the
excessive mucus gland secretion, wherein the mucus secretion is not
a symptom of rhinorrhea.
DETAILED DESCRIPTION
[0022] The Botulinum toxins used according to the present invention
are Botulinum toxins type A, B, C, D, E, F and G.
[0023] The physiologic groups of Clostridium botulinum types are
listed in Table I.
1TABLE I Physiologic Groups of Clostridium botulinum Phenotypically
Toxin Glucose Phages Related Sero- Milk Fermen- & Clostridium
Group Type Biochemistry Digest tation Lipase Plasmids
(nontoxigenic) I A, B, F proteolytic saccharolytic + + + + C.
sporogenes nonproteolytic saccharolytic II B, E, F psychotrophic -
+ + + III C, D nonproteolytic saccharolytic .+-. + + + C. novyi IV
G proteolytic nonsaccharolytic + - - - C. subterminale
[0024] These toxin types may be produced by selection from the
appropriate physiologic group of Clostridium botulinum organisms.
The organisms designated as Group I are usually referred to as
proteolytic and produce Botulinum toxins of types A, B and F. The
organisms designated as Group II are saccharolytic and produce
Botulinum toxins of types B, E and F. The organisms designated as
Group III produce only Botulinum toxin types C and D and are
distinguished from organisms of Groups I and II by the production
of significant amounts of propionic acid. Group IV organisms only
produce neurotoxin of type G. The production of any and all of the
Botulinum toxin types A, B, C, D, E, F and G are described in
Chapter 1 of Botulinum Neurotoxin and Tetanus Toxin, cited above,
and/or the references cited therein. Botulinum toxins types B, C,
D, E, F and G are also available from various species of
clostridia.
[0025] Currently fourteen species of clostridia are considered
pathogenic. Most of the pathogenic strains produce toxins which are
responsible for the various pathological signs and symptoms.
Organisms which produce Botulinum toxins have been isolated from
botulism outbreaks in humans (types A, B, E and F) and animals
(types C and D). Their identities were described through the use of
specific antitoxins (antibodies) developed against the earlier
toxins. Type G toxin was found in soil and has low toxigenicity.
However, it has been isolated from autopsy specimens, but thus far
there has not been adequate evidence that type G botulism has
occurred in humans.
[0026] Preferably, the toxin is administered by means of
intramuscular injection directly into a local area such as a
spastic muscle, preferably in the region of the neuromuscular
junction, although alternative types of administration (e.g.,
subcutaneous injection), which can deliver the toxin directly to
the affected region, may be employed where appropriate. The toxin
can be presented as a sterile pyrogen-free aqueous solution or
dispersion and as a sterile powder for reconstitution into a
sterile solution or dispersion.
[0027] Where desired, tonicity adjusting agents such as sodium
chloride, glycerol and various sugars can be added. Stabilizers
such as human serum albumin may also be included. The formulation
may be preserved by means of a suitable pharmaceutically acceptable
preservative such as a paraben, although preferably it is
unpreserved.
[0028] It is preferred that the toxin is formulated in unit dosage
form; for example, it can be provided as a sterile solution in a
vial or as a vial or sachet containing a lyophilized powder for
reconstituting a suitable vehicle such as saline for injection.
[0029] In one embodiment, the Botulinum toxin is formulated in a
solution containing saline and pasteurized human serum albumin,
which stabilizes the toxin and minimizes loss through non-specific
adsorption. The solution is sterile filtered (0.2 micron filter),
filled into individual vials and then vacuum-dried to give a
sterile lyophilized powder. In use, the powder can be reconstituted
by the addition of sterile unpreserved normal saline (sodium
chloride 0.9% for injection).
[0030] The dose of toxin administered to the patient will depend
upon the severity of the condition; e.g., the number of muscle
groups requiring treatment, the age and size of the patient and the
potency of the toxin. The potency of the toxin is expressed as a
multiple of the LD.sub.50 value for the mouse, one unit (U) of
toxin being defined as being equivalent to that amount of toxin
that kills 50% of a group of 18 to 20 female Swiss-Webster mice,
weighing between 17-22 grams each.
[0031] The dosages used in human therapeutic applications are
roughly proportional to the mass of muscle being injected.
Typically, the dose administered to the patient may be up from
about 0.01 to about 1,000 units; for example, up to about 500
units, and preferably in the range from about 80 to about 460 units
per patient per treatment, although smaller of larger doses may be
administered in appropriate circumstances such as up to about 50
units for the relief of pain and in controlling cholinergic
secretions.
[0032] As the physicians become more familiar with the use of this
product, the dose may be changed. In the Botulinum toxin type A,
available from Porton, DYSPORT, 1 nanogram (ng) contains 40 units.
1 ng of the Botulinum toxin type A, available from Allergan, Inc.,
i.e., BOTOX.RTM., contains 4 units. The potency of Botulinum toxin
and its long duration of action mean that doses will tend to be
administered on an infrequent basis. Ultimately, however, both the
quantity of toxin administered and the frequency of its
administration will be at the discretion of the physician
responsible for the treatment and will be commensurate with
questions of safety and the effects produced by the toxin.
[0033] In some circumstances, particularly in the relief of pain
associated with sports injuries, such as, for example,
charleyhorse, botulinum type F, having a short duration activity,
is preferred.
[0034] Mucus coats many epithelial surfaces and is secreted into
fluids such as saliva. Mucus is composed chiefly of mucins and
inorganic salts suspended in water. Mucus adheres to many
epithelial surfaces where it serves as a diffusion barrier against
contact with noxious substances (such as gastric acid and smoke)
and as a lubricant to minimize shear stresses. Mucus coatings are
particularly prominent on the epithelia of the respiratory,
gastrointestinal and genital tracts, including on the cervix. Mucus
is also an abundant and important component of saliva. Mucus
secreting cells are widely distributed through the body. Thus,
goblet cells are abundant in the epithelium of the gastrointestinal
and respiratory tracts and mucous glands in these same organs
deliver their products through ducts into the intestine and
respiratory system. Between 0.01 units (i.e. of a botulinum toxin
type A) and 5,000 units (i.e. of a botulinum toxin type B) of a
botulinum toxin can be local administered to treat an excessive
mucus secretion (where the excessive mucus secretion in not due to
rhinorrhea) such as an excessive mucus secretion by the
gastrointestinal tract, genital tract or by the respiratory tract.
Rhinorrhea is characterized by a free discharge of thin, nasal
mucus, due to inflamed or infected sinuses. U.S. Pat. No. 5,766,605
discusses use of a botulinum toxin to treat a symptom of
rhinorrhea. A treatment of an excessive mucus secretion according
to the present invention excludes treatment of rhinorrhea because
of inter alia: (a) the possibility that local administration of a
botulinum toxin to the highly vascularized nasal mucosal cells can
result in entry of botulinum toxin into the systemic circulation;
(b) the considerable sensitivity of inflamed nasal mucosal glands
to local administration of a pharmaceutical, and; (c) the typically
brief duration of the condition of rhinorrhea (days), as compared
to the longevity of the effect of administration of a botulinum
toxin (months).
[0035] The invention will now be illustrated by reference to the
following nonlimiting examples.
[0036] In each of the examples, appropriate areas of each patient
are injected with a sterile solution containing the confirmation of
Botulinum toxin. Total patient doses range from about 0.01 units to
about 10,000 units (i.e. of type B toxin) of a botulinum toxin.
Before injecting any muscle group, careful consideration is given
to the anatomy of the muscle group, the aim being to inject the
area with the highest concentration of neuromuscular junctions, if
known. Before injecting the muscle, the position of the needle in
the muscle is confirmed by putting the muscle through its range of
motion and observing the resultant motion of the needle end.
General anaesthesia, local anaesthesia and sedation are used
according to the age of the patient, the number of sites to be
injected, and the particular needs of the patient. More than one
injection and/or sites of injection may be necessary to achieve the
desired result. Also, some injections, depending on the muscle to
be injected, may require the use of fine, hollow, teflon-coated
needles, guided by electromyography.
[0037] Following injection, it is noted that there are no systemic
or local side effects and none of the patients are found to develop
extensive local hypotonicity. The majority of patients show an
improvement in function both subjectively and when measured
objectively.
EXAMPLE 1
The Use of Botulinum Toxin Type in the Treatment of Tardive
Dyskinesia
[0038] A male patient, age 45, suffering from tardive dyskinesia
resulting from the treatment with an antipsychotic drug, such as
Thorazine or Haldol, is treated with 150 units of Botulinum toxin
type B by direct injection of such toxin into the facial muscles.
After 1-3 days, the symptoms of tardive dyskinesia, i.e., orofacial
dyskinesia, athetosis, dystonia, chorea, tics and facial grimacing,
etc. are markedly reduced.
Example 1(a)
[0039] The method of Example 1 is repeated, except that a patient
suffering from tardive dyskinesia is injected with 50-200 units of
Botulinum toxin type C. A similar result is obtained.
Example 1(b)
[0040] The method of Example 1 is repeated, except that a patient
suffering from tardive dyskinesia is injected with 50-200 units of
Botulinum toxin type D. A similar result is obtained.
Example 1(c)
[0041] The method of Example 1 is repeated, except that a patient
suffering from tardive dyskinesia is injected with 50-200 units of
Botulinum toxin type E. A similar result is obtained.
Example 1(d)
[0042] The method of Example 1 is repeated, except that a patient
suffering from tardive dyskinesia is injected with 50-200 units of
Botulinum toxin type F. A similar result is obtained.
Example 1(e)
[0043] The method of Example 1 is repeated, except that a patient
suffering from tardive dyskinesia is injected with 50-200 units of
Botulinum toxin type G. A similar result is obtained.
EXAMPLE 2
The Use of Botulinum Toxin Type B in the Treatment of Spasmodic
Torticollis
[0044] A male, age 45, suffering from spasmodic torticollis, as
manifested by spasmodic or tonic contractions of the neck
musculature, producing stereotyped abnormal deviations of the head,
the chin being rotated to one side, and the shoulder being elevated
toward the side at which the head is rotated, is treated by
injection with 100-1,000 units of Botulinum toxin type E. After 3-7
days, the symptoms are substantially alleviated; i.e., the patient
is able to hold his head and shoulder in a normal position.
Example 2(a)
[0045] The method of Example 2 is repeated, except that a patient
suffering from spasmodic torticollis is injected with 100-1,000
units of Botulinum toxin type B. A similar result is obtained.
Example 2(b)
[0046] The method of Example 2 is repeated, except that a patient
suffering from spasmodic torticollis is injected with 100-1,000
units of Botulinum toxin type C. A similar result is obtained.
Example 2(c)
[0047] The method of Example 2 is repeated, except that a patient
suffering from spasmodic torticollis is injected with 100-1,000
units of Botulinum toxin type D. A similar result is obtained.
Example 2(d)
[0048] The method of Example 2 is repeated, except that a patient
suffering from spasmodic torticollis is injected with 100-1,000
units of Botulinum toxin type E. A similar result is obtained.
Example 2(e)
[0049] The method of Example 2 is repeated, except that a patient
suffering from spasmodic torticollis is injected with 100-1,000
units of Botulinum toxin type F. A similar result is obtained.
Example 2(f)
[0050] The method of Example 2 is repeated, except that a patient
suffering from spasmodic torticollis is injected with 100-1,000
units of Botulinum toxin type G. A similar result is obtained.
EXAMPLE 3
The Use of Botulinum Toxin in the Treatment of Essential Tremor
[0051] A male, age 45, suffering from essential tremor, which is
manifested as a rhythmical oscillation of head or hand muscles and
is provoked by maintenance of posture or movement, is treated by
injection with 50-1,000 units of Botulinum toxin type B. After two
to eight weeks, the symptoms are substantially alleviated; i.e.,
the patient's head or hand ceases to oscillate.
Example 3(a)
[0052] The method of Example 3 is repeated, except that a patient
suffering from essential tremor is injected with 100-1,000 units of
Botulinum toxin type C. A similar result is obtained.
Example 3(b)
[0053] The method of Example 3 is repeated, except that a patient
suffering from essential tremor is injected with 100-1,000 units of
Botulinum toxin type D. A similar result is obtained.
Example 3(c)
[0054] The method of Example 3 is repeated, except that a patient
suffering from essential tremor is injected with 100-1,000 units of
Botulinum toxin type E. A similar result is obtained.
Example 3(d)
[0055] The method of Example 3 is repeated, except that a patient
suffering from essential tremor is injected with 100-1,000 units of
Botulinum toxin type F. A similar result is obtained.
Example 3(e)
[0056] The method of Example 3 is repeated, except that a patient
suffering from essential tremor is injected with 100-1,000 units of
Botulinum toxin type G. A similar result is obtained.
EXAMPLE 4
The Use of Botulinum Toxin in the Treatment of Spasmodic
Dysphonia
[0057] A male, age 45, unable to speak clearly, due to spasm of the
vocal chords, is treated by injection of the vocal chords with
Botulinum toxin type B, having an activity of 80-500 units. After
3-7 days, the patient is able to speak clearly.
Example 4(a)
[0058] The method of Example 4 is repeated, except that a patient
suffering from spasmodic dysphonia is injected with 80-500 units of
Botulinum toxin type C. A similar result is obtained.
Example 4(b)
[0059] The method of Example 4 is repeated, except that a patient
suffering from spasmodic dysphonia is injected with 80-500 units of
Botulinum toxin type D. A similar result is obtained.
Example 4(c)
[0060] The method of Example 4 is repeated, except that a patient
suffering from spasmodic dysphonia is injected with 80-500 units of
Botulinum toxin type E. A similar result is obtained.
Example 4(d)
[0061] The method of Example 4 is repeated, except that a patient
suffering from spasmodic dysphonia is injected with 80-500 units of
Botulinum toxin type F. A similar result is obtained.
Example 4(e)
[0062] The method of Example 4 is repeated, except that a patient
suffering from spasmodic dysphonia is injected with 8-500 units of
Botulinum toxin type G. A similar result is obtained.
EXAMPLE 5
The Use of Botulinum Toxin Types A-G in the Treatment of Excessive
Sweating, Lacrimation or Mucus Secretion or Other Cholinergic
Controlled Secretions
[0063] A male, age 65, with excessive unilateral sweating is
treated by administering 0.01 to 50 units, of Botulinum toxin,
depending upon degree of desired effect. The larger the dose,
usually the greater spread and duration of effect. Small doses are
used initially. Any serotype toxin alone or in combination could be
used in this indication. The administration is to the gland nerve
plexus, ganglion, spinal cord or central nervous system to be
determined by the physician's knowledge of the anatomy and
physiology of the target glands and secretary cells. In addition,
the appropriate spinal cord level or brain area can be injected
with the toxin (although this would cause many effects, including
general weakness). Thus, the gland (if accessible) or the nerve
plexus or ganglion are the targets of choice. Excessive sweating,
tearing (lacrimation), mucus secretion or gastrointestinal
secretions are positively influenced by the cholinergic nervous
system. Sweating and tearing are under greater cholinergic control
than mucus or gastric secretion and would respond better to toxin
treatment. However, mucus and gastric secretions could be modulated
through the cholinergic system. All symptoms would be reduced or
eliminated with toxin therapy in about 1-7 days. Duration would be
weeks to several months.
[0064] An excessive intestinal mucus secretion can be treated by
injecting about 40 units of a botulinum toxin type A or about 2000
units of a botulinum toxin type B into the hyperactive intestinal
mucosa.
EXAMPLE 6
The Use of Botulinum Toxin Types A-G in the Treatment of Muscle
Spasms in Smooth Muscle Disorders Such As Sphincters of the
Cardiovascular Arteriole, Gastrointestinal System, Urinary or Gall
Bladder, Rectal, Etc.
[0065] A male, age 30-40, with a constricted pyloric valve which
prevents his stomach from emptying, is treated by administering
1-50 units of Botulinum toxin. The administration is to the pyloric
valve (which controls release of stomach contents into the
intestine) divided into 2 to 4 quadrants, injections made with any
endoscopic device or during surgery. In about 1-7 days, normal
emptying of the stomach, elimination or drastic reduction in
regurgitation occurs.
EXAMPLE 7
The Use of Botulinum Toxin Types A-G in the Treatment of Muscle
Spasms and Control of Pain Associated with Muscle Spasms in
Temporal Mandibular Joint Disorders
[0066] A female, age 35, is treated by administration of 0.1 to 50
units total of Botulinum toxin. The administration is to the
muscles controlling the closure of the jaw. Overactive muscles may
be identified with EMG (electromyography) guidance. Relief of pain
associated with muscle spasms, possible reduction in jaw clenching
occurs in about 1-3 days.
EXAMPLE 8
The Use of Botulinum Toxin Types A-G in the Treatment of Muscle
Spasms and Control of Pain Associated with Muscle Spasms in
Conditions Secondary to Sports Injuries (Charleyhorse)
[0067] A male, age 20, with severe cramping in thigh after sports
injury is treated by administration of a short duration toxin,
possible low dose (0.1-25 units) of preferably type F to the muscle
and neighboring muscles which are in contraction ("cramped").
Relief of pain occurs in 1-7 days.
EXAMPLE 9
The Use of Botulinum Toxin Types A-G in the Treatment of Muscle
Spasms and Control of Pain Associated with Muscle Spasms in Smooth
Muscle Disorders Such as Gastrointestinal Muscles
[0068] A female, age 35, with spastic colitis, is treated with
1-100 units of Botulinum toxin divided into several areas, enema
(1-5 units) delivered in the standard enema volume, titrate dose,
starting with the lowest dose. Injection is to the rectum or lower
colon or a low dose enema may be employed. Cramps and pain
associated with spastic colon are relieved in 1-10 days.
EXAMPLE 10
The Use of Botulinum Toxin Types A-G in the Treatment of Muscle
Spasms and Control of Pain Associated with Muscle Spasms in
Spasticity Conditions Secondary to Stroke, Traumatic Brain or
Spinal Cord Injury
[0069] A male, age 70, post-stroke or cerebral vascular event, is
injected with 50 to 300 units of Botulinum toxin in the major
muscles involved in severe closing of hand and curling of wrist and
forearm or the muscles involved in the closing of the legs such
that the patient and attendant have difficulty with hygiene. Relief
of these symptoms occurs in 7 to 21 days.
EXAMPLE 11
The Use of Botulinum Toxin Types A-G in the Treatment of Patients
with Swallowing Disorders
[0070] A patient with a swallowing disorder caused by excessive
throat muscle spasms is injected with about 1 to about 300 units of
Botulinum toxin in the throat muscles. Relief the swallowing
disorder occurs in about 7 to about 21 days.
EXAMPLE 12
The Use of Botulinum Toxin Types A-G in the Treatment of Patients
with Tension Headache
[0071] A patient with a tension headache caused by excessive throat
muscle spasms is injected with about 1 to about 300 units of
Botulinum toxin in muscles of the head and upper neck. Relief of
the tension headache occurs in about 1 to about 7 days.
[0072] Although there has been hereinabove described a use of
Botulinum toxins for treating various disorders, conditions and
pain, in accordance with the present invention, for the purpose of
illustrating the manner in which the invention may be used to
advantage, it should be appreciated that the invention is not
limited thereto since many obvious modifications can be made, and
it is intended to include within this invention any such
modifications as will fall within the scope of the appended claims.
Accordingly, any and all modifications, variations, or equivalent
arrangements which may occur to those skilled in the art, should be
considered to be within the scope of the present invention as
defined in the appended claims.
* * * * *