U.S. patent application number 12/943294 was filed with the patent office on 2011-11-17 for cosmetic use of botulinum toxin for the treatment of eyebrow and forehead ptosis, and unwanted eyebrow expression.
Invention is credited to KENNETH D. STEINSAPIR.
Application Number | 20110280978 12/943294 |
Document ID | / |
Family ID | 38661433 |
Filed Date | 2011-11-17 |
United States Patent
Application |
20110280978 |
Kind Code |
A1 |
STEINSAPIR; KENNETH D. |
November 17, 2011 |
COSMETIC USE OF BOTULINUM TOXIN FOR THE TREATMENT OF EYEBROW AND
FOREHEAD PTOSIS, AND UNWANTED EYEBROW EXPRESSION
Abstract
A method of temporarily elevating the eyebrow position and
softening undesirable glabellar muscle activity to affect a more
desirable appearance. In a broad aspect the invention comprises
injecting small quantities of botulinum toxin (BTX) dissolved in
microdroplets of injectable saline carrier to treat the septal and
orbital orbicularis oculi muscles, on each side of a patient's
face. In sufficient numbers, injected microdroplets of BTX are able
to selectively weaken these muscles. This method preferably also
includes using microdroplets of BTX to treat: a) the depressor
supercilii muscle, on each side; b) the procerus muscle; c) the
corrugator supercilii muscle, on each side; and d) the inferior
limit of the frontalis muscle where it meets the superior aspect of
the orbital portion of the orbicularis oculi muscle.
Inventors: |
STEINSAPIR; KENNETH D.; (LOS
ANGELES, CA) |
Family ID: |
38661433 |
Appl. No.: |
12/943294 |
Filed: |
November 10, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11429057 |
May 4, 2006 |
7846457 |
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12943294 |
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Current U.S.
Class: |
424/780 |
Current CPC
Class: |
Y02A 50/30 20180101;
A61Q 19/08 20130101; A61K 8/64 20130101; Y02A 50/469 20180101; C12Y
304/24069 20130101; A61K 38/4893 20130101 |
Class at
Publication: |
424/780 |
International
Class: |
A61K 38/16 20060101
A61K038/16; A61Q 90/00 20090101 A61Q090/00 |
Claims
1. A method of temporarily elevating the eyebrow position and
softening undesirable glabellar muscle activity to effect a more
desirable appearance, comprising: injecting small quantities of
botulinum toxin (BTX) dissolved in microdroplets of injectable
saline carrier to treat the septal and orbital orbicularis oculi
muscles, on each side of a patient's face, said microdroplets in
large enough numbers being sufficient to selectively weaken these
muscles.
2. The method of claim 1, further including the step of injecting
small quantities of BTX dissolved in microdroplets to treat the
depressor supercilii muscle, on each side.
3. The method of claim 1, further including the step of injecting
small quantities of BTX dissolved in microdroplets to treat the
procerus muscle.
4. The method of claim 1, further including the step of injecting
small quantities of BTX dissolved in microdroplets to treat the
corrugator supercilii muscle, on each side.
5. The method of claim 1, further including the step of injecting
small quantities of BTX dissolved in microdroplets to treat the
inferior limit of the frontalis muscle where it meets the superior
aspect of the orbital portion of the orbicularis oculi muscle.
6. The method of claim 1, further including the steps of injecting
small quantities of BTX dissolved in microdroplets to treat: a) the
depressor supercilii muscle, on each side; b) the procerus muscle;
c) the corrugator supercilii muscle, on each side; and d) the
inferior limit of the frontalis muscle where it meets the superior
aspect of the orbital portion of the orbicularis oculi muscle.
7. The method of claim 1, wherein said microdroplet injections are
placed 0.5 to 1 millimeter below the skin surface to distribute the
BTX between the skin and the underlying muscles to limit the
diffusion of the BTX.
8. The method of claim 1, wherein the BTX is locally administered
using microdroplet volumes of BTX solution in amounts between about
0.01 milliliters and 0.05 milliliters.
9. The method of claim 1, wherein the botulinum toxin (BTX) is
selected from the group consisting of botulinum toxin types A, B,
C, D, E, F, and G as produced by the Clostridium botulinum
bacterium.
10. The method of claim 1, wherein the BTX is botulinum toxin A
(BTX-A).
11. The method of claim 1, wherein each microdroplet injected
contains 0.001 to 1.0 Units of Botulinum toxin A adjusted based on
the desired degree of muscle weakening.
12. The method of claim 1, wherein the concentration of the BTX
solution prepared for microdroplet administration is adjusted based
on the relative strength of the BTX product used and the desired
degree of muscle weakening.
13. The method of claim 1, wherein each microdroplet contains 0.25
to 0.5 Units of BTX-A.
14. The method of claim 1, wherein 30 to 90 microdroplet injections
are distributed over the muscle groups to be treated.
15. The method of claim 1, wherein the distribution of the
microdroplet injections are adjusted to enhance brow shape and
symmetry.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This is a continuation of U.S. Ser. No. 11/429,057 entitled
"Cosmetic Use of Botulinum Toxin for the Treatment of Eyebrow and
Forehead Ptosis, and Unwanted Eyebrow Expression", filed May 4,
2006. The content of U.S. Ser. No. 11/429,057 is incorporated by
reference herein in its entirety.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates generally to the cosmetic use
of neurotoxin agents and more particularly to an improved method
for injecting botulinum toxin (BTX).
[0004] 2. Description of the Related Art
[0005] The position and appearance of the eyebrows is determined at
rest and dynamically by the opposing action of several groups of
muscles that act on the eyebrow. The frontalis muscle primarily
performs eyebrow elevation. Brow elevation is opposed by the septal
and orbital portions of the orbicularis oculi muscle, including the
depressor supercilii component of the orbicularis oculi muscle, and
the procerus muscle (D. Knize (1996) An anatomically based study of
the mechanisms of eyebrow ptosis; Plast. Reconstr. Surg.
97:1321-33). The medial position of the eyebrow is also determined
by the activity of the corragator supercilii muscle. Additionally
the shape of the brows is also determined by the activities of the
eyebrow elevators and the eyebrow depressor muscles where they
interdigitate along the eyebrow to create facial expression (A.
Karacalar, et al (2005) Compensatory brow asymmetry: anatomic study
and clinical experience; Aesthetic Plast. Surg 29: 119-23).
[0006] An aesthetically pleasing appearance is associated with
relatively few lines in the forehead, no creasing between the
eyebrows at the root of the nose, commonly known as the worry line,
no lines across the bridge of the nose, and an absence of facial
lines lateral to the eyes, commonly known as crow's feet.
Additionally, with age there is a gradual fall in the position of
the eyebrows creating hooding over the upper eyelids, which is
known as brow ptosis. Aesthetically this change makes the eyes look
small and is not desirable. Hooding of the upper eyelids by the
descending eyebrow tissue results in a neural reflex that increases
the activity of the frontalis muscle in an effort to keep the
vision clear of the descending tissue that would otherwise obstruct
vision or interfere with eyelid function (S. Teske, et. al. (1998)
Hering's law and eyebrow position; Ophthal. Plast. Reconstr. Surg.
14: 105-6).
[0007] Botulinum toxin (BTX), which is produced by the bacterium
Clostridium botulinum, inhibits the release of acetylcholine at the
neuromuscular junction weakening muscle contraction. The degree of
muscle paralysis will vary with the intensity of neuromusclular
blockade. Several immunologically distinct botulinum toxin
serotypes have been identified including A, B, C, D, E, F, and G.
They vary in the severity and duration of the neuromuscular
blockade and, consequently, the severity of the paralysis they
produce (J. Melling, et. al. (1988) Clostridium botulinum toxins:
nature and preparation for clinical use; Eye 2: 16-23). The term
BTX is the generic term for this family of neurotoxins. Botulinum
toxin A (BTX-A) is currently available from two commercial sources:
Allergan Inc., Irvine, Calif., under the trade name BOTOX.RTM., and
from Ipsen Ltd., Slough, UK under the trade names Dysport.RTM. and
Reloxin.RTM.. Botulinum toxin B (BTX-B) is available from Solstice
Neurosciences, Inc, South San Francisco, Calif., under the trade
name Myobloc.RTM.. The relative strengths of these products vary.
For purposes of clarity, dose and dilutions in the following
discussions will refer to the widely available botulinum toxin A
product by Allergan Inc. (BOTOX.RTM.). The dose and dilution must
be adjusted for the other commercially available botulinum products
according to their relative strength.
[0008] The first clinical application of botulinum toxin was by Dr.
Allan Scott for the treatment of strabismus and then for a form of
localized eyelid dystonia known as blepharospasm (A. Scott, et. al.
(1973) Pharmacologic weakening of extraocular muscles; Invest
Ophthalmol. 12:924-7). These were the first clinical applications
approved by the FDA for treatment with botulinum toxin A (P. Savino
and M. Maus (1991) Botulinum toxin therapy; Neurol. Clin.
9:205-24). Clinical use of botulinum toxin A in the treatment of
spastic facial disorders lead to the clinical observation that many
of the treated patients had improvement in the deep glabellar
furrows between the eyebrows (J. Carruthers and A. Carruthers
(1992) Treatment of glabellar frown lines with C. botulinum-A
exotoxin; J. Dermatol. Surg. Oncol. 18:17-21). Recently, FDA
approval was granted for the cosmetic use of botulinum toxin A for
the treatment of the worry line between the eyebrows. Other FDA
indications for botulinum toxin A include treatment for cervical
dystonia, a type of neck spasm, and axillary hyperhydrosis, also
known as excessive armpit sweating (R. Bhidayasiri and D. Truong
(2005) Expanding use of botulinum toxin; J. Neurol. Sci.
235:1-9).
[0009] Botulinum toxin A is clinically used more broadly than what
is approved by the FDA. This wider usage is permissible for
licensed physicians and is referred to as "off label" use (J.
Carruthers and A. Carruthers (2004) Botox: beyond wrinkles; Clin.
Dermatol. 22:89-93). Cosmetically, BTX is used to soften dimpling
in the chin, relax the depressor anguli oris muscle that
contributes to a turned down corners of the mouth as detailed by
Carruthers in U.S. Pat. No. 6,358,917, and a range of locations and
effects around the eyes and in the forehead. Previously, BTX has
been used to elevate the eyebrow position by treating between the
eyebrows and at the lateral eyebrow with relatively few injection
sites (2-4) and with relatively large quantities of BTX (1.5-2.5
Units Botulinum toxin A) (W. Huang, et. al. (2000) Browlift with
botulinum toxin; Dermatol. Surg. 26:55-60). This technique is
limited by fear of inducing the undesired side effect of ptosis of
the upper eyelid, where the upper eyelid droops causing visual
obstruction. This can be caused by the unwanted diffusion of BTX
into the eyelid affecting the levator palpebrae superioris muscle
responsible for eyelid elevation (A. Trindade De Alemeida and S.
Cernea (2001) Regarding browlift with botulinum toxin; Dermatol.
Surg. 27:848-849).
[0010] As will be disclosed below, the present inventor has found
that it is possible to treat the eyebrow depressors extensively yet
avoid the unwanted side effects by using a microdroplet injection
technique and trapping the injected BTX between the skin and the
orbicularis oculi muscle, the most important eyebrow depressor.
SUMMARY OF THE INVENTION
[0011] The present invention is a method of temporarily elevating
the eyebrow position and softening undesirable glabellar muscle
activity to affect a more desirable appearance. In a broad aspect
the invention comprises injecting small quantities of botulinum
toxin (BTX) dissolved in microdroplets of injectable saline carrier
to treat the septal and orbital orbicularis oculi muscles, on each
side of a patient's face. In sufficient numbers, injected
microdroplets of BTX are able to selectively weaken these muscles.
This method preferably also includes using microdroplets of BTX to
treat: a) the depressor supercilii muscle, on each side; b) the
procerus muscle; c) the corrugator supercilii muscle, on each side;
and d) the inferior limit of the frontalis muscle where it meets
the superior aspect of the orbital portion of the orbicularis oculi
muscle. As the term is used herein, a microdroplet is defined as
0.01 to 0.05 milliliters of injectable saline, which is used as an
injectable carrier for a dissolved quantity of BTX, creating a BTX
solution. The quantity of BTX dissolved in a microdroplet will vary
with the BTX product chosen and the clinical effect desired. BTX is
highly potent so that even with the highest doses of BTX used
clinically, the solution comprising the microdroplet will be mostly
water by weight and volume. While the quantity of BTX in a
microdroplet may vary from 0.001 to 1.0 Units of botulinum toxin A
(BOTOX.RTM., Allergan Inc.), in the preferred embodiment, a
microdroplet will typically contain 0.25 to 0.5 Units of botulinum
toxin A. As noted above, microdroplets of other botulinum toxin
products must be adjusted by the number of Units based on their
relative strength.
[0012] The microdroplet injections are preferably placed
approximately 0.5 to 1 millimeter below the skin surface to
distribute the BTX between the skin and the underlying muscle to
limit the diffusion of the BTX.
[0013] The present method alleviates or improves eyebrow ptosis.
This method makes use of the fact that the orbital orbicularis
oculi muscle inserts into the skin and therefore resides just below
the dermis layer of the skin. Small quantities of BTX placed
superficially by needle between the dermis and the orbicularis
oculi muscle will tend to be trapped at the site of placement
causing a more localized effect than larger quantities of BTX
injected deep to the orbicularis oculi muscle. Limiting the volume
and quantity of BTX injected into each site further reduces the
risk of BTX diffusion.
[0014] As noted above, the microdroplet injection volume at each
site is in a range between 0.01 to 0.05 ml. Each microdroplet of
BTX injected contains 0.001 to 1.0 Units of botulinum toxin A
adjusted based on the desired degree of muscle weakening. In the
current preferred embodiment, the BTX solution is prepared so that
each microdroplet contains 0.25 to 0.5 Units of botulunum toxin A.
Typical total dosages of BTX-A administered during a treatment vary
between 25-75 Units adjusted based on the muscle mass of the
individual being treated and the desired degree of muscle
weakening. The cumulative effect of these microdroplet injections
of BTX is selective weakening of the eyebrow depressor effect of
the orbicularis oculi muscle, including the depressor supercilli
portion of this muscle. The microdroplet treatment also preferably
includes the procerous muscle and the corragator muscle to weaken
all of the muscles at the orbital rim that contribute to eyebrow
depression.
[0015] The method of BTX administration of the present invention
makes it possible to extensively treat the area below the eyebrow
without unwanted side effects. Previous treatments methods avoided
this area because they commonly produced a fall in the position of
the eyelid with visual obstruction known as upper eyelid
ptosis.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] FIG. 1 is an illustration of the facial muscles showing the
location of the muscles to be injected in accordance with the
principles of the present invention.
[0017] FIG. 2 illustrates a typical periocular microdroplet BTX
treatment, in accordance with the principles of the present
invention, in which each individually injected microdroplet is
depicted with a circle.
[0018] FIG. 3 is an illustration of the cross-section of the orbit
that shows the relationship of the levator palbepra superioris
muscle to the orbicularis oculi muscle.
DETAILED DESCRIPTION OF THE INVENTION
[0019] Botulinum toxin is a general term for any of the neurotoxins
produced by any of the members the bacterial organisms that belong
to the Clostridium botulinum species. Fourteen pathogenic strains
of this species have been isolated from botulism outbreaks in
humans and animals. These organisms have been shown to produce
seven immunologically distinct types of neurotoxin (types A, B, C,
D, E, F, and G). The term "BTX" is used to refer to this family of
neurotoxins. Currently only botulinum toxin types A and B are
commercially available for clinical use: Botulinum toxin A from
Allergan Inc., Irvine, Calif., under the trade name BOTOX.RTM., and
from Ipsen Ltd., Slough, UK, under the trade name Dysport.RTM. and
Reloxin.RTM.. Botulinum toxin B is available from Solstice
Neurosciences, Inc, South San Francisco, Calif., under the trade
name Myobloc.RTM..
[0020] The treatment dose of BTX is measured in "Unit" equivalents,
which is defined on the basis of a biological assay. One Unit
equivalent is defined as the mean LD.sub.50 (the dose that is
lethal for 50% of the animals tested) for female Swiss Webster mice
with a weight of 18-20 grams (Schantz E J, Kaultner D A (1978)
Standardized assay for Clostridium botulinum toxins. J Assoc Anal
Chem 61:96-99. The estimated LD.sub.50 for BOTOX.RTM. (botulinum
toxin A) for a 70 kg adult human is 2800 Units (40 Units/kg).
Dysport.RTM. is roughly ten times less potent than the BOTOX.RTM.
product. The Botulinum toxin B product Myobloc.RTM. is 30 to 50
times less potent than the BOTOX.RTM. product. Consequently, the
dose of these agents must be adjusted to achieve an equivalent
treatment effect.
[0021] Commercially available BTX-A comes in a unit dose form that
is reconstituted just prior to use. Currently the only BTX-A
approved by the FDA is BOTOX.RTM. from Allergan Inc. This product
is packaged in a 100 Unit vial as a sterile lyophilized powder
stored at 8 degrees C. or less until use. The toxin is dissolved
with unpreserved normal saline (sodium chloride 0.9% for injection)
just prior to use to form a solution of a given dilution based on
the volume of saline used to reconstitute the BTX-A. The
manufacturer recommends that it be used within 4 hours after
reconstitution to avoid loss of potency. The saline is introduced
after breaking the vacuum present in the unit vial to avoid foaming
of the solution, which may affect the potency.
[0022] The vial that the commercially available BTX products come
in have a rubber stopper which permits the reconstituted solution
to be drawn up without removing the rubber stopper that seals the
vial. This stopper is cleaned with an alcohol wipe and allowed to
dry. An 18-gauge needle on a tuberculin type syringe is used to
draw up the desired volume of solution. In the case of BOTOX.RTM.,
the concentration of the solution is determined by the quantity of
saline used to reconstitute the BTX-A in the vial. For this method,
typically 2 to 4 ml of unpreserved saline are used to reconstitute
the lyophilized product. These volumes of dilution produce
concentrations that vary from 25 Units to 50 Units per milliliter
or 2.5 Units to 5 Units per 0.1 milliliter or 0.25 to 0.5 Units per
0.01 milliliter. Prior to treatment the 18-gauge needle is removed
and replaced with a 30, 31 or 32 gauge needle with 8 to 13 mm
length. The presently available BTX-B product comes as a solution
containing 5000 Units per milliliter and can be diluted as
needed.
[0023] Referring now to FIG. 1, an illustration of the facial
muscles is shown, illustrating the location of the muscles to be
injected and other surrounding muscles. The muscles to be injected
include portions of the orbicularis oculi muscle, designated
generally as 1, including the orbital portion 1a and the septal
portion 1b. The tarsal portion 1c is generally avoided to prevent
weakness of lid closure. Other muscles preferably injected include
the depressor supercilli muscle 2, the procerous muscle 3, the
frontalis muscle 4, the corragator supercilli muscle 5, and d) the
inferior limit of the frontalis muscle where it meets the superior
aspect of the orbital portion 1a of the orbicularis oculi muscle
(as shown by numeral designation 6). Treatment of the frontalis
muscle is strictly limited to the inferior portion on each side
that interdigitates with the opposing orbital portion of the
orbicularis oculi muscle. Interaction of these two muscle groups at
this location is responsible for muscular pinching along the
eyebrow, which is generally undesirable.
[0024] Patients are typically seated upright in a chair with a
headrest to prevent movement. The skin is typically lightly
anesthetized with a topical anesthetic or with ice. Next the skin
is cleaned with alcohol and allowed to dry. A tuberculin syringe
holds 1 milliliter of solution. The needle is inserted just below
the dermis, which along the eyebrow is one millimeter below the
skin surface. The goal is to place the medication between the skin
and the muscle to be treated. A microdroplet of BTX is injected at
each site. Each microdroplet contains 0.001 to 1.0 Units of
botulinum toxin A (BOTOX.RTM., Allergan Inc.) in 0.01 to 0.05
milliliters of injectable saline. In the preferred embodiment of
the invention, the typical microdroplet will contain 0.25 to 0.5
Units of BTX-A. Very little diffusion of the BTX occurs when the
medication is placed in this fashion.
[0025] FIG. 2 demonstrates a typical treatment pattern, with each
individually injected micro-droplet depicted with a circle (circles
being designated by numeral designations 7). Patients are advised
not to massage the area or work out for 24 hours to further reduce
the likelihood of dissipation of the toxin. The total dose of BTX-A
may vary from 10 Units to 100 Units depending on the individual
treatment plan. Most patients benefit from doses in the range of 30
to 60 Units. A total treatment may require between 30 and 100
treatment sites.
[0026] In contrast, prior described applications of BTX along the
brow have made no attempt to keep the agent placed between the skin
and the muscle and rely on larger aliquots of medication. (A. Chen
and A. Frankel (2003) Altering brow contour with botulinum toxin;
Facial Plast. Surg. Clin. North Am. 11: 457-64). Consequently, the
injected BTX can diffuse creating unwanted side effects. In
particular, injections below the eyebrow have been avoided because
the risk of diffusion of the agent into the eyelid causing unwanted
weakening of the levator palebebrae superioris, the muscle that
raises the eyelid, producing an unwanted droop of the eyelid (S.
Huilgol, A. Carruthers, and J. Carruthers (1999) Raising eyebrows
with botulinum toxin; Dermatol. Surg. 1999: 373-5).
[0027] Referring to FIG. 3, the close proximity of the levator
palebebrae superioris muscle 8 and its tendon 9 to the orbital 1a,
septal 1b, and tarsal 1c portions of the orbicularis oculi muscle 1
can be appreciated. By placing low volume microdroplets of BTX with
as little as 0.01 milliliters of volume just below the dermis,
unwanted diffusion and side effects are avoided. This permits
treatment of larger areas of the orbicularis oculi muscle in the
upper eyelid and below the eyebrow which results in an elevation of
the eyebrow tissue in a manner that is not possible with previously
described techniques that specifically avoid treating this area. It
is the use of microdroplets of BTX solution placed just below the
skin surface that makes the treatment of this area possible. By
weakening a much larger percentage of the orbicularis oculi muscle,
the muscle primarily responsible for eyebrow depression, in the
upper eyelid above the eyelid crease, in the sub-eyebrow area, at
and just above the eyebrow, laterally in the crows feet area and
along the medial aspect of the nose in this controlled manner, a
profound forehead lift is possible. This degree of lift is not
achievable with previously described methods without the risk of
affecting the levator palebebrae superioris muscle deep in the
eyelid that is responsible for elevating the upper eyelid. When
diffusion of BTX deep into the eyelid occurs, partial or complete
paralysis of the upper eyelid can occur preventing the opening of
the eyelid. This undesired effect while temporary is unacceptable
to those being treated.
[0028] The microdroplet method can also be used to treat the
depressor supercilli, procerus muscle and the corrugators, which
also contribute to brow depression in the center of the brow region
over the root of the nose.
[0029] Other embodiments and configurations may be devised without
departing from the spirit of the invention and the scope of the
appended claims.
* * * * *