Note: Descriptions are shown in the official language in which they were submitted.
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COSMETIC USE OF BO7'ULINUM TOXIN FOR
TREAT142ENT OF DOVVNTURNED MOUTH
5= FIELD OF THE PP/Ell-MON
This invention relates to cosmetic uses of neuroparalytic toxins.
BACKGROUND OF TIIE INVENTION
Marionette lines are cosmetic defects of the human face often caused by a
loss of derrnal collagen in the lower lips and chin area as a result of aging.
These
lines are usually accompanied by a downturn at the corners of the mouth,
producing
a"sadA appearance, hence the term "sad mouth". In this condition, the
horizontal
symmetry of the mouth is offset in a downward or inferior directzon as a
result of
the downturn at the corners of the mouth.
Some facial wrinkles and unsightly facial expressions are due to overactivity
of the underlying facial musculature. Neuroparalytic toxins have been used for
treatment of wrinkles and in other treatments for facial rejuvenation. A toxin
capable of bloclcing neuromuscular activity is administered to a facial muscle
responsible for the facial defect or lesion. Resulting paralysis of the facial
muscle
alleviates the facial defect. The preferred toxin for cosmetic use is
Botulinum toxin
(BTX).
BTX, produced by the bacterium Clostridlum botulinurn reversibly paralyzes
striated muscle when administered in sub-lethal doses. BTX has been used in
the
treatment in a number of neuromuscular disorders and conditions involving
muscular spasm including various forms of dystonia, hemifacial spasm, tremor,
spasticity (e.g. resulting from Multiple sclerosis), anal fismres and various
ophthalmologic conditions (c.f. A. Carruthers et at (1996), Botulinum A
Exotoxin
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Use in Clinical Dermatology; Journal of the American Academy of Dermatology
34: 788-797).
BTX is a generic term covering a family of toxins produced by C. botulinum
comprising up to eight serologically distinct forms (A, B, C,, C2, D, E, F and
G).
These toxins which are among the most powerfiul neuroparalytic agents known
(c.f. Melling, J. et al (1988) Clostridium Botulinum: Nature and Preparation
for
Clinical Use; Eye 2: 16-23). Serotypes A, B and F are the most potent. The
mode
of action is to inhibit the release of acetylcholine by the presynaptic nerve.
BTX-A serotyn is available commercially under the trademarks BOTOXTm
(Allergan, Inc., Irvine, California, U.S.A.) and DYSPORT' (Speywood
Phannaceuticals, Ltd., Maidenhead, U.K.). The initial cosmetic use of BTX was
for treatment of forehead frown lines as reported in J. Carruthers and A.
Carrttthers
(1992) "Treatment of G1abeBar Frown I.ines witb C. Botnlinum A Exotoxin";
J. Dermatol. Surg. Oncol. 18: 17-21. Subsequently, various facial treatments
employing BTX have been reported but use of BTX for treatment of midfacial
defects has been limited.
Application of BTX near the mouth has been limited to treatment of
neuromuscular disorder. For example, hemifacial spasm has been treated by BTX
injection to the zygomaticus muscle but the modeolus adjacent the corner of
the
mouth is avoided (J. Carruthers and A. Carruthers (1996) Bomlimun A Exotoxin
in
Clinical Ophthalmology; Can. J. Ophthalmol. 31: 389-400).
It has been reported that BTX injection to a group of muscles on one side of
a patient's face has been used to treat facial synicfnesis and vertical
asymmetry
caused by facial nerve palsy (Armstrong, M.W.J. et al. (1996) "Treatment of
Facial
Synkinesis and Facial Asymmetry with Botulinum Toxin Type A Following Nerve
Palsy", Clin. Otolaryngol. 21:15-20). In the latter procedure, the levator
anguli
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oris, zygoinaticus major, rizorius and depressor anguli oris muscles
associated with
the mouth together with various muscles associated with the eye on the normal
side
of a patient's face were all treated as a group in order to affect the entire
vertical
symmetry of a patient's face to compensate for effects of nerve palsy on the
untreated side of the face.
While BTX treatment of the platysma muscle has -been performed for
treatment of neck lines and banding, it has also been noted that injection of
BTX
into the platysma produces an uplift of the mouth (F.S. Brandt and B. Bellman
(1998) Cosmetic Use of Botulinum A Exotoxin for the Aging Neck; Dermatol.
Surg. 24: 1232-1234). Injection of BTX into the point of the 'chin has also
been
done for treatment of prominent mental crease (A. Carruthers and J.
Carruthers;
"Cosmetic Uses of Botulinum A Exotoxin"; In: James, W.D.. et al Eds. Advances
in Dermatology (1997) Mosby-Yearbook, Chicago: at pages 325-48).
The inventors have now found that "sad mouth" may be treated by
simultaneous bilateral BTX injection to depressor anguli oris (triangularis)
muscle
(termed herein DAO) thereby affectizig the horizontal symmetry of the mouth,
without embarrassment to the appearance and function of the mouth. The normal
function of the patient's lips is not impeded.
SUMMARY OF THE I1ITVENTION
This invention provides the use of Botulinum toxin (BTX) to cause paralysis
of a depressor anguli oris (DAO) musculature in a patient to alleviate
downturn at
corners of the patient's mouth.
This invention provides Aimthod of alleviating downtura of corners of a
patient's mouth comprising:
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a) locating a depressor anguli oris (DAO) muscle adjacent each corner
of said mouth; and
b) injecting into a DAO adjacent each corner of the mouth, a quantity of
Botulinum toxin (BTX) sufficient to cause paralysis of a DAO.
In this invention, BTX is simultaneously injected into each DAO adjacent
each corner of the patient's mouth. By simultaneously, it is meant that the
injection
into each DAO occurs as part of the same treatment, although a DAO on one side
of
the mouth may be selected for injection before the other DAO during a
treatment
session.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1: is a frontal view showing musculature of the human face and
neck.
Figure 2: is a frontal view of a human face and neck showing the
general location of the DAO muscles and sites for BTX
injection according to this invention.
DETAILED DESCRIPTION OF EMBODIIVIENTS OF THE 1NVENTION
The term "BTX" as used herein includes any neurotoxin produced by
C. botulinum or derivatives thereof. Preferably, the neurotoxin will be the
Botulinum A exotoxin, termed herein "BTX-A".
The term "Unit equivalents" as used herein, is an amount of BTX which is
equivalent to staniarcl Units of BTX-A. A standard Unit of BTX-A is defined as
the
mean L..D50 for female Swiss Webster mice weighing 18-20 grams (E.J. Schantz
and
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D.A. Kaultner (1978) Standardized Assay for Clostridium botulinum Toxins;
J. Assoc. Anal. Chem. 61: 96-99). The estimated human LD50 for a 70-kg person
is
40 Units/kg or about 2500-3000 Units.
BOTOXTM is sold in 100 Unit vials. DYSPC3RTTM is sold in 500 Unit vials.
For cosmetic uses, the vial contents are typically diluted i or 2 ml of with
sterile
saline solution, which for BOTOV' provides a 100 or 50 Unitlml dilution.
DYSPORTTm BTX-A is rougWy tenfold less toxic than BOTOXTm and
approxzrnately fourfold greater amounts of the DYSPORT' product will usually
be
injected to achieve the same result as would is obtained using a specific
number of
Units of BOTOX"m.
Commercially available toxin is typically freeze dried and is stored froxen
(e.g. at -4 C) until ready for use. The toxin is diluted just prior to use.
The
resulting solution should be used within several hours of preparation. Care
should
be taken to avoid foaming of the solution by slowing the entry of saline into
the
vacuum of the storage vial. The solution should not be shaken. Once used,
remaining toxin, vial, needles and syringes should be disposed of in a manner
appropriate for biohazardous waste.
Typical injection technique involves the use of a short, narrow needle
(e.g. ih inch or 8mnn; 30-gage) with an insulin or taberculzn type syringe.
Patients
are typicaily treated in the seated position. The skin area is cleaned with an
alcohol
swab. A single syringe may be used for multiple injections to treat different
locations in a single muscle or different locations on a patient's face.
Typically, the
plunger of the syringe is depressed as the needle is withdrawn so that toxin
is evenly
distributed at the injection site. Pressure or gentle massage may be applied
at the
injection site to assist in dissipating the toxin. The toxin wiIl typically
migrate
approximately 1 cm from the site of injection.
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Electromyographic (EMG) guided needles may be used for injection to
determine needle location of a high de;;ree of accuracy, although this
technique is
generally not necessary nor is it required in the instant invention.
In prior applications of BTX, i:otal dose per treatment is variable and is
largely dependent upon the condition being treated and the site of application
of
BTX. For example, a total dose of 20-30 Units will typically be applied to the
glabellar complex and 60-75 Units for platysmal bands (c.f. A. Carruthers and
J. Carruthers (1998) History of the Cosmetic Use of Botulinum A Exotoxin;
Dermatol. Surg. 24: 1168-1170). Doses of up to 200 Units per treatment session
for the platysma have been reported (Brandt and Bellman [supra]). In prior
applications, a typical dose at a single injection point is approximately 5
Units of
toxin in a 100 Unitlml dilution.
Onset of muscle paralysis follow:ing injection usually occurs within hours of
treatment. The duration of paralysis will vary from patient to patient.
Typically,
duration will be from 2-8 months before subsequent treatment is required to
alleviate
the condition.
This invention provides a succes:,ful treatment of Marionette lines and "sad
mouth" by BTX injection into the DAO. In such treatment, the orbicularis oris
muscle surrounding the mouth is normally avoided in view of its sensitivity to
BTX.
However, the orbicularis oris muscle may be treated in conjunction with this
invention to alleviate severe upper lip lines or wrinkles. In such a case, a
small
amount of BTX is injected into the orbicularis oris, with the total dose being
in the
order of 4 Units for the entire upper lip. In general, care must be used in
BTX
treatments close to the mouth because of i_he danger of producing a flaccid
cheek, an
incompetent mouth, or an asymmetric smile.
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The DAO may be found by instructing the patient to voluntarily and forcibly
pull down the corners of the mouth. The DAO can be then felt by pulling
inferiorly
at a point approximately 1 c3n lateral and 8 nun inferior to the commissure.
Alternatively, EMG localization may be performed.
Treatment should take into consideration the pre-existing symmetry bf the
mouth and is performed on both sides of the' face in order to provide a
symmetric
result. The required dosage to each side of the mouth should be judged and if
necessary, altered upon re-treatment.
Injection may be made into any part of the DAO musculature. The injection
is intramuscular and may be performed using the injection techniques used for
other
BTX treatments as descn'bed above. On a typical patient's face, the preferred
point
of injection into the DAO will be approximately 7 mm laterally and 8 mm.
inferior
from the corner of the mouth. A single injection witl usually suff'ice with
the dosage
for a single DAO muscle ranging from 2#101) Units - 5(f109b) iTnits. Tlie best
dose will depend upon the sex of the patient and size of the individual.
Typical
doses for a female will be 2( 10%) Units - 3(f10%) Units for one side of the
mouth; and, for a male, 3(t10gb) Units .- 5 (t10%) Units for'one side of the
mouth.
Contraindications for the use of BTX are known in the art and include
children under 12, pregnancy, lactation, history of . neuromuscular disease
and
known sensitivity to BTX or human albumin. This invention is not be
recommended for patients who are singers, musicians and other individuals who
use
their perioral muscles with intensity. However, treatment according to this
invention will normally not affect normal, speech, whistling or mastication
particularly in cases where the orbicularis oris is not treated.
Follawing application of this invention, laser resurfacing techniques may be
employed to enhance the effect. In the . case of very deep - Marionette lines,
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performance of this invention may be followed by soft tissue filling treatment
such
as collagen, Hylaform", Restlyanel (soft forrn) or Gore Tex7 implants.
The drawings may be referred to for illustration of performance af this
invention. Figure 1 shows the location of various facial muscles and
anatomical
locations referred to herein, including: the DAO 1; orbicularis oris 2;
zygomaticus
3; and, the modeolus 4. The platysma, which overlies the neck muscles and
extends
in part, to region 5, is not illustrated in Figure 1.
In Figure 2, region(s) 6 bounded by dashed lines illustrate the general
location on the patient's skin which overly the DAO. Suitable injection sites
include
the areas within region(s) 6 that are marked with a "X".
While the following claims are intended to recite the features of the
invention, it will be apparent to those of skill in the art that certain
changes may be
made without departing from the scope of this invention.
