U.S. patent application number 11/703269 was filed with the patent office on 2007-09-27 for method for treating cellulite.
This patent application is currently assigned to The Research Foundation of the State University of New York. Invention is credited to Marie A. Badalemente, Alexander B. Dagum.
Application Number | 20070224184 11/703269 |
Document ID | / |
Family ID | 38325147 |
Filed Date | 2007-09-27 |
United States Patent
Application |
20070224184 |
Kind Code |
A1 |
Badalemente; Marie A. ; et
al. |
September 27, 2007 |
Method for treating cellulite
Abstract
The invention relates to the discovery that collagenase
injections are effective in dissolving and lysing the collagenase
septa network in the skin that comprises cellulite. As such, the
invention relates to methods of treating cellulite in a patient in
need of such treatment comprising injecting or otherwise delivering
the effective amount of purified collagenase to the collagenase
septa network of cellulite in the skin. The invention also relates
to the use of collagenase in the manufacture of a medicament to
treat cellulite of the skin.
Inventors: |
Badalemente; Marie A.;
(Mount Sinai, NY) ; Dagum; Alexander B.; (Stony
Brook, NY) |
Correspondence
Address: |
THE FARRELL LAW FIRM, P.C.
333 EARLE OVINGTON BOULEVARD
SUITE 701
UNIONDALE
NY
11553
US
|
Assignee: |
The Research Foundation of the
State University of New York
Stony Brook
NY
|
Family ID: |
38325147 |
Appl. No.: |
11/703269 |
Filed: |
February 7, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60775690 |
Feb 22, 2006 |
|
|
|
Current U.S.
Class: |
424/94.63 |
Current CPC
Class: |
A61K 8/66 20130101; A61K
2800/91 20130101; A61P 43/00 20180101; A61K 38/4886 20130101; A61P
17/00 20180101; A61Q 19/06 20130101; A61K 2800/30 20130101; A61P
3/06 20180101; A61P 3/00 20180101 |
Class at
Publication: |
424/094.63 |
International
Class: |
A61K 38/48 20060101
A61K038/48 |
Goverment Interests
GOVERNMENT SUPPORT
[0002] The invention was supported, in part, by a grant M01RR10710
from the National Institutes of Health. The U.S. Government has
certain rights in the invention.
Claims
1. A method of treating cellulite in a subject in need of such
treatment, the method comprising delivering an effective amount of
purified collagenase to the collagenous septa network of
cellulite.
2. The method according to claim 1, wherein the collagenase
(Clostridiopeptidase A) is derived from the bacterium Clostridium
hisolyticum.
3. The method according to claim 1, wherein the purified
collagenase is administered alone.
4. The method according to claim 1, wherein the purified
collagenase is administered in an absence of traimcinolone or other
corticosteroids.
5. The method according to claim 1, wherein the purified
collagenase is injected in a dose comprising at least about 700 SRC
units, applied in one or more injections.
6. The method according to claim 1, wherein the purified
collagenase is injected in a dose comprising at least about 1000
SRC units, applied in one or more injections.
7. The method according to claim 1, wherein the purified
collagenase is injected in a dose comprising at least about 1500
SRC units, applied in one or more injections.
8. The method according to claim 1, wherein the purified
collagenase is injected in a dose comprising at least about 10000
ABC units, applied in one or more injections.
9. The method according to claim 1, wherein the purified
collagenase is injected in a volume of about 1.0 ml.
10. The method according to claim 1, wherein the purified
collagenase is injected at multiple sites.
11. The method according to claim 1, wherein the purified
collagenase is comprised of collagenase I and collagenase II.
12. The method, according to claim 9, wherein the injection is
delivered in the area of cellulite, characterized by skin
dimpling.
13. The method according to claim 1, wherein the subject is a human
patient.
14. The method according to claim 1, wherein the treatment is
repeated after about four to six weeks.
15. The method according to claim 1, wherein after one month of
receiving at least one administration of collagenase, the patient
achieves a significant visual reduction in the appearance of
cellulite.
16. The method according to claim 1, wherein the purified
collagenase is injected in a dose comprising from about 500 SRC
units/mg to about 15,000 SRC units/mg, applied in one or more
injections.
Description
PRIORITY
[0001] This application claims priority to application Ser. No.
60/775,690, which was filed with the U.S. Patent and Trademark
Office on Feb. 22, 2006.
BACKGROUND OF THE INVENTION
[0003] Dimpling of the skin or the "mattress phenomenon" of the
thighs and buttocks is commonly referred to as cellulite. This
condition is common and appears in otherwise healthy individuals
afflicting women much more frequently than men. Over the counter
topical therapies abound for the elimination of cellulite. These
products and other over the counter topical applications have
proved to be useless, costly, and in fact, have never undergone
proper placebo controlled clinical trials. Recent randomized,
placebo controlled trails of topical retinol and retinol containing
caffeine and ruscogenine have also failed to show merit for the
elimination of cellulite.
[0004] If the treatment of cellulite is to be successful, then the
basic pathophysiology of the condition requires clear definition.
It was only in 1999 that Rosenbaum, et al. undertook an
investigation of the morphology and biochemistry of cellulite
(Rosenbaum, M. Prieto, V., Hellmer, J., Boschmann, M., Krueger, J.,
Leibel, R. L., Ship, A. G., An Exploratory Investigation of the
Morphology and Biochemistry of Cellulite, Plastic & Reconst
Surg 101(7): 1934-9, 1998). Seven healthy adult subjects, five
women and two men, four affected, three unaffected, underwent
sonography of the thigh, measurement of regional in vivo
subcutaneous adipose tissue metabolism and full thickness wedge
biopsy of the thigh under local anesthesia. The presence of
cellulite was defined as evidence of dimpling of the skin of the
posterolateral thigh. Any continuous area of skin at least 3 cm in
diameter in which no dimpling was evident was designated as
unaffected. In all affected individuals studies were performed to
include both affected and unaffected areas of the thigh.
Microscopic examination of the wedge biopsies and in vivo
sonographic examination of the thigh both showed a diffuse pattern
of extrusion of underlying adipose tissue and to the retinacular
dermis in affected, but not unaffected, subjects. The study also
demonstrated that women had a diffuse pattern of irregular and
discontinuous connective tissue immediately below the dermis but
the same layer of connective tissue was smooth and continuous in
men. This connective tissue layer was more irregular and
discontinuous in affected vs. unaffected individuals. No
significant differences were noted in subcutaneous adipose tissue
morphology, lipolytic responsiveness, or regional blood flow
between affected and unaffected sites within individuals. This
study demonstrated that there is a sexual dimorphism in the
structural characteristics of the dermal connective tissue that
pre-disposes women to develop the irregular extrusion of adipose
tissue into the dermis which characterized cellulite. This study
concluded that there was no evidence of any primary role for
adipose tissue physiology, blood flow or adipose tissue
biochemistry in the etiology of cellulite but that the connective
tissue of the female thigh and buttocks is structured to accentuate
differences in small sub-dermal adipose tissue deposits.
[0005] This conclusion was substantiated by the work of Pierard, et
al. who examined 39 autopsy specimens microscopically
(Pierard-Franchimont, C., Pierard G. E., Henry, F., Vroome, V.
& Cauwenbergh, G. A Randomized, Placebo-Controlled Trial of
Topical Retinol in the Treatment of Cellulite, Amer. J. Clin.
Dermatology, 1(6):369-74, 2000). Their control group consisted of
four adult women and eleven adult men showing no evidence of
cellulite. They state that the lumpy aspect of the dermal
hypodermal interface appeared to represent a gender linked (female)
characteristic of the thighs and buttocks. Cellulite was identified
by this mattress phenomenon microscopically and presented as
focally enlarged fibrosclerotic strands partitioning the subcutis.
They speculated that these structures might represent a reactive
process to sustained hypodermal pressure caused by fat
accumulation.
[0006] In a more recent study by Querleux, et al. the anatomy and
physiology of subcutaneous adipose tissue by in vivo magnetic
resonance imaging and spectroscopy was studies in relation to sex
and the presence of cellulite (Querleux, B., Cornillon, C.,
Jolivet, O., Bittoun, J., Anatomy and Physiology of Subcutaneous
Adipose Tissue by in vivo Magnetic Resonance Imaging and
Spectroscopy: Relationship with Sex and Presence of Cellulite, Skin
Research And Tech 8(2):118-124, May 2002). These authors concluded
that 3D reconstruction of the fibrous septae network showed a
higher percentage of septae in the direction perpendicular to the
skin surface in women with cellulite.
[0007] There remains no effective treatment of cellulite up to
date. It is the object of invention to provide such methods for
treatment of cellulite.
SUMMARY OF THE INVENTION
[0008] The invention relates to the discovery that collagenase
injections are effective in lysing the collagen septae network of
cellulite in humans to treat cellulite and restore a smooth skin
appearance. The invention related to methods of treating cellulite
in a subject in need of such treatment, which involves injecting an
effective amount of purified collagenase in the manufacture of a
medicament to treat cellulite. The collagenase is preferably
purified and substantially free of other enzymes, such as proteases
and/or hyaluronidase.
DETAILED DESCRIPTION OF THE INVENTION
[0009] The invention related to the discovery that collagenase
injections are effective in lysing the collagen septae network of
cellulite in humans to treat cellulite and restore a smooth skin
appearance. The invention relates to methods of treating cellulite
in a subject in need of such treatment, which involves injecting an
effective amount of collagenase to the thigh and/or buttocks. The
invention also relates to the use of collagenase in the manufacture
of a medicament to treat cellulite.
[0010] Collagenase injections have been proposed for the treatment
of diseases such as Dupuytren's disease, adhesive capsulitis and
Peyronie's disease. These diseases are all associated with collagen
cords or plaques. (Wegman, Thomas L. U.S. Pat. No. 5,589,171 Dec.
31, 1996, U.S. Pat. No. 6,086,872 Jul. 11, 2000, U.S. Pat. No.
6,022,539, Feb. 8, 2000, Adhesive Capsulitis-patent Pending, all of
which are incorporated herein by reference in their entirety).
[0011] Collagenase injections have also been proposed for the
treatment of cellulite when combined with hyaluronidase, a soluble
enzyme product prepared from mammalian testes (see Pinelle, Sheldon
R. U.S. Pat. No. 4,645,668 Mar. 27, 1985). The patent disclosed one
working example for cellulite with a low dose of collagenase (100
units) in combination with hyaluronidase (150 units) for only in
female patient. No further details in the improvement of cellulite
after the injections was presented.
[0012] The use of intralesional injection of purified Clostridial
collagenase has been shown to be clinically safe and effective in
clinical trials in Dupuytren's disease in correcting the flexion
contracture deformity of the hand(s). Additionally, the use of
extracapsular injection of purifies Clostridial collagenase has
been shown to be clinically safe and effective in the treatment of
adhesive capsulitis (frozen shoulder) in clinical trials in
restoring injection has also been used by others in clinical trials
in Peyronie's disease, a contracture deformity of the penis.
[0013] The published work of the inventor, Dr. Badalamente, in
Dupuytren's disease forms the rationale for the proposed invention
(Starkweather, K., Lattuga, S., Hurst, L. C., Badalamente, M. A.,
Guilak, F., Sampson, S. P., Dowd, A., Wisch, D. Collagenase in the
Treatment of Dupuvtren's Disease: An in vitro Study, J. Hand Surg.
21A:490-95, 1996; Badalamente, M. A., Hurst, L. C., Enzyme
Injection as a Non-operative Treatment for Dupuytren's Disease, J.
Drug-Delivery 3(1):35-40, 1996; Hurst, L. C., Badalamente, M. A.
(invited authorship) Non-operative Treatment of Dupuytren's
Disease, Hand Clinics, G. M. Rayan (ed). W.B. Saunders 15(1),
97-107, 1999; Hurst, L. C., Badalamente, M. A. (invited editors
& authorship), Dulpuytren's Disease, R. Tubinana, R. Tubiana,
C. Leclercq, L. C. Hurst, M. A. Badalamente (eds), Martin Dunitz
Publisher, London (2000); Badalamente, M. A., Hurst, L. C. Enzyme
Iniection as a Non-operative Treatment of Dupuytren's Disease, J.
Hands Surg. 25A(4); 629-36, 2000; Badalamente, M. A., Hurst, L. C.,
Hentz, V. R. Collagen as a Clinical Target: Non-operative Treatment
of Dupuytren's Disease, J. Hand Surg. 27A(5):788-98, 2002) In
Dupuytren's disease, the pathognomonic fibrous cord is often
interspersed with a septa-like arrangement of adipose tissue. These
present clinically as mattress-type "lumps" of varying sizes and in
Dupuytren's disease, are termed nodules. It has been a consistent
clinical finding in both Phase 2 and 3 trials for Dupuytren's
disease that after purified Clostridial collagenase injection, not
only does the collagenous cord dissolve and rupture when subjected
to pressure in extention, but the fibro-fatty nodules, also
resolve, and harmlessly resorb. Therefore, collagenase injected
subcutaneously into an area of cellulite was postulated to be a
safe and effective treatment for this condition in restoring a
smooth appearance of the skin of the thighs and/or buttocks.
[0014] Collagenase is an enzyme that has specific ability to digest
collagen. A preferred form of a collagenase is derived from
fermentation by Clostridium histoliticum and is purified by a
chromatographic technique, such as that disclosed in U.S.
Application Ser. No. 60/763,470 filed on Jan. 20, 2006 (Attorney
Docket Number 4024.3001 US), which is incorporated herein by
reference. Collagenase naturally produced by Clostridium
histoliticum once purified will exhibit tow distinct peaks when run
on an electrophoresis SDS gel. It is these two distinct peaks that
are referred to as collagenase I and collagenase II.
[0015] Sterilized lyophilized collagenase powder is commercially
available having a minimum assay of 50 units per mg. The assay may
range considerably above that from batch to batch, but is taken
into account in determining the weight of the powder to use with a
pharmaceutically acceptable carrier, for example, normal saline, in
preparing a desired concentration for treatment.
[0016] The collagenase is applied in a liquid carrier that is
pharmaceutically acceptable, including inertness towards the
collagenase. Examples are normal saline, aqueous, NaCl/CaCl.sub.2
buffer, aqueous dextran solution, aqueous hetastarch solution.
[0017] One form of the Purified Collagenase used for Injection, is
comprised of two microbial collagenases, referred to as
"Collagenase ABC I" and "Collagenase ABC II". Both collagenases are
isolated and purified from the fermentation of the bacterium
Clostidium histolyticum and belong to the same metalloprotease.
[0018] Collagenase ABC I is a single polypeptide chain consisting
of approximately 1000 amino acids of known sequence. It has an
observed molecular weight of 115 kiloDalton (kD), an isoelectric
point (pI) between 5.63-5.68 and an extinction coefficient of
1.480. From its activity behavior toward synthetic substrate, it
has been determined that Collagenase ABC I is the class I
Clostidium histolyticum collagenase in the literature.
[0019] Collagenase ABC II is also a single polypeptide chain
consisting of about 1000 amino acids of deduced sequence. It has an
observed molecular weight of 110 kD, an isoelectric point between
5.46-5.57 and an extinction coefficient of 1.576. Collagenase ABC
II functionally belongs to the class II Clostidium histolyticum
collagenase in the literature.
[0020] The drug substance may have a 1 to 1 mass ratio for
collagenase ABC-I and ABC-II with an extinction coefficient of
1.528. Both collagenases require tightly bound zinc and loosely
bound calcium for their activity. Collagenase ABC I and Collagenase
ABC II are not immunologically crossreactive and have a very broad
hydrolyzing reactivity toward all types of collagen. Even though
each collagenase shows different specificity, together they
synergistic activity toward collagen.
[0021] Lyophilized Collagen for Injection is purified clostridial
collagenase prepared as lyophilized formulation and may contain
about 0.1 mg lactose monohydrate USP per 1,000 ABC units of
collagenase activity.
[0022] A preferred collagenase composition comprises a mixture of
collagenase I and collagenase II in a mass ratio of about 1 to 1
and having specific activity from about 500 SRC units/mg to about
15,000 SRC units/mg, preferably of at least about 700 SRC units/mg,
more preferably of at least about 1000 SRC units/mg, even more
preferably at least about 1500 SRC units/mg. One SRC unit will
solubilize rat tail collagen into ninhydrin reaction material
equivalent to 1 nanomole of leucine per minute, at 25 degrees, C,
pH 7.4. Collagenase has been described in ABC units as well. The
potency assay of collagenase is based on the digestion of
undenatured collagen (from bovine tendon) at pH 7.2 and 37 degrees
C. for 20-24 hours. The number of peptide bonds cleaved are
measured by reaction with ninhydrin. Amino groups released by a
solubilize digestion control are subtracted. One net ABC unit of
collagenase will solubilize ninhydrin reactive material equivalent
to 1.09 nanomoles of leucine per minute. One SRC unit equals
approximately 6.3 ABC units.
[0023] The collagenase is preferably administered via injection in
a liquid carrier that is pharmaceutically acceptable. Preferably,
the carrier does not interact or deactivate the collagenase.
Examples are normal saline, aqueous NaCl/CaCl, buffer (containing
0.9% NaC 1 and 2 mM CaCl.sub.2). For example, the lyophilized
formulation can contain 0.1 mg lactose monohydrate per 1,000 ABC
units. Each glass vial used below contained 5,150 ABC units
collagenase.
[0024] In accordance with the invention, collagenase in a liquid
carrier is injected into an area of cellulite in the subject's
posterolateral thigh. The amount and concentration of collagenase
used is effective to lyse and dissolve the collagen septa network
of the cellulite.
[0025] The injection is a sterile one and does not exceed 1.0 ml.
The total dosage is injected at five different points into the
posterolateral thigh where the cellulite dimples of the thigh are
most apparent. The objective is to assure good distribution of the
collagenase. Patients preferably rest on the contra lateral thigh,
in bed, for about one, preferably two hours or more.
[0026] In other embodiments, the collagenase can be administrated
locally or topically, such as, a transdermal patch or topical cream
or topical ointment to the area of cellulite or can be administered
via an implant, such as, microcapsules or michrospheres which
release collagenase over time.
[0027] In one embodiment, the patient is characterized as having an
area of at least 10.times.10 cm of cellulite on the posterolateral
thigh. The invention can achieve improvement in restoring normal
and smooth skin appearance in the 10.times.10 cm are of cellulite
on the posterolateral though.
[0028] In another embodiment of the present invention, collagenase
can be administrated locally or topically, such as, a transdermal
patch or topical cream or topical ointment to the area of cellulite
or can be administered via an implant, such as, microcapsules or
michrospheres which release collagenase over time and is
administered in the absence of traimcinolone or other
corticosteroids.
[0029] In cases where results of a single treatment are considered
inadequate, the same procedures, total amount of collagenase and
concentration may be repeated at 4-6 weeks intervals. Areas of
cellulite, other than the posterolateral thigh may also require
treatment, or repeated treatment at 4-6 week intervals. For
example, the front of the thigh and the buttocks may contain areas
of cellulite.
Experimental
[0030] Methods
[0031] Ten patients entered the study protocol, all females, mean
age 41=10 years. The mean body mass index (BMI) was 28.
[0032] The minimum are of cellulite of the posterolateral thigh
needed for inclusion was 10.times.10 cm. All patients had areas of
cellulite of the posterolateral thigh which exceeds the minimum
10.times.10 cm area. Baseline digital photographs were taken of the
treatment area. In a sterile fashion, 10,000 ABC units (0.58 mg)
were injected at five points in the 10.times.10 cm target cellulite
area. The total fluid volume of the injection was 1.0 ml. The
buffer used was sterile 0.9% NaCL and 2 mM CaCl.sub.2. All patients
are flowed post injection, at one day, one week, one, three, and
six months. Post treatment photographs are taken serially.
[0033] Patients had the option of choosing to have a similar
collagenase injection on the opposite side, for cosmetic symmetry,
when they reached the time interval of 4-6 weeks post the first
collagenase injection. Qualification of the reduction/elimination
of cellulite in the target area of the thigh was by visual
inspection and photographic documentation.
[0034] The target area of the cellulite treated was divided into
four equal quadrants in the 10.times.10 cm target treatment area.
Reduction/elimination of cellulite in the target treatment area was
quantified by visual inspection by quadrant, e.g., 4/4=no quadrants
responded to treatment, 3/4=three quadrants responded to treatment,
2/4 two quadrants responded to treatment, 1/4=one quadrant
responded to treatment, 0/4=all quadrants responded to treatment.
The actual are in cm of any remaining cellulite of the
posterolateral target area of cellulite was also measured.
Photographs were also used for documentation.
[0035] Results
[0036] All patients experienced a reduction in cellulite of the
target thigh after collagenase injection. Table 1 shows the results
of the reduction in the cellulite in the quadrants of the thighs in
the patients treated. There was significant reduction in cellulite
appearance of the injected are. Cellulite are was reduced by 77% by
day 1 in comparison to baseline. This result was sustained in the
longer term. In comparison to baseline, cellulite area was reduced
by 74% at 1 week, by 89% at 1 month, by 86% at 3 months and by 76%
at 6 months.
[0037] Adverse events included tenderness in the injection area,
ecchymosis and mild edema which resolved well in the mean of 10, 18
and 6 days respectively. TABLE-US-00001 Patient 1 day 1 week 1 mo 3
mo 6 mo # Age Sex Thigh Parameter Baseline post 1.sup.st post
1.sup.st post 1.sup.st post 1.sup.st post 1.sup.st LY C-009 37 F
Right BMI 33 33 34 34 34 36 Circumference 68 68 68 68 68 69 (cm)
Area (cm) 12 .times. 14 12 .times. 14 5 .times. 5 5 .times. 5 5
.times. 5 8 .times. 9 Quadrants 4 4 2 2 2 3 Patient 1 day 1 week 1
mo 3 mo 6 mo # Age Sex Thigh Parameters Baseline post 2.sup.nd post
1.sup.st post 1.sup.st post 1.sup.st post 1.sup.st NW C-001 52 F
Right BMI 32 31 31 31 32 32 Circumference 68 66 64 64 64 64 (cm)
Area (cm) 16 .times. 12 2 .times. 2 5 .times. 5 0 5 .times. 1 5
.times. 1 Quadrants 4 1 2 0 1 1 Patient 1 day 1 week 1 mo 3 mo 6 mo
# Age Sex Thigh Parameter Baseline post 2.sup.nd post 2.sup.nd post
2.sup.nd post 2.sup.nd post 2.sup.nd NW C-001 52 F Left BMI 32 32
32 32 31 30 Circumference 68 68 69 66 63 63 (cm) Area (cm) 19
.times. 19 19 .times. 19 5 .times. 5 0 4 .times. 0 0 Quadrants 4 4
2 0 1 0 Patient 1 day 1 week 1 mo 3 mo 6 mo # Age Sex Thigh
Parameter Baseline post 1.sup.st post 1.sup.st post 1.sup.st post
1.sup.st post 1.sup.st PD C-004 44 F Left BMI 24 24 25 24 25 25
Circumference 57 65 66 63 56 56 (cm) Area (cm) 10 .times. 10 0 0 4
.times. 3 4 .times. 3 4 .times. 3 Quadrants 4 0 0 1 1 1 Patient 1
day 1 week 1 mo 3 mo 6 mo # Age Sex Thigh Parameter Baseline post
2.sup.nd post 2.sup.nd post 2.sup.nd post 2.sup.nd post 2.sup.nd PD
C-004 44 F Right BMI 25 25 25 25 25 Circumference 60 62 62 62 62
(cm) Area (cm) 10 .times. 10 0 1 .times. 4 0 0 Quadrants 4 0 1 0 0
Patient 1 day 1 week 1 mo 3 mo 6 mo # Age Sex Thigh Parameter
Baseline post 1.sup.st post 1.sup.st post 1.sup.st post 1.sup.st
post 1.sup.st AP C-012 54 F Right BMI 23 23 23 23 Lost to
Circumference 56 56 56 52 followup (cm) Area (cm) 10 .times. 11 3
.times. 9 3 .times. 5 5 .times. 4 Quadrants 4 2 1 1 ER C-015 44 F
Left BMI 22 22 22 22 21 Circumference 51 54 52 53 53 (cm) Area (cm)
10 .times. 10 5 .times. 9 4 .times. 10 0 0 Quadrants 4 2 3 0 0 AE
C-016 40 F Right BMI 31 31 31 31 31 30 Circumference 67 79 72 69 68
64 (cm) Area (cm) 12 .times. 12 0 9 .times. 5 2 .times. 3 2 .times.
7 2 .times. 7 Quadrants 4 0 3 1 2 2 Patient 1 day 1 week 1 mo 3 mo
6 mo # Age Sex Thigh Parameter Baseline post 2.sup.nd post 2.sup.nd
post 2.sup.nd post 2.sup.nd post 2nd AE C-016 40 F Left BMI 31 31
31 31 31 Circumference 69 71 68 68 68 (cm) Area (cm) 12 .times. 14
0 2 .times. 4 1 .times. 2 0 Quadrants 4 0 1 1 0 Patient 1 day 1
week 1 mo 3 mo 6 mo # Age Sex Thigh Parameter Baseline post
1.sup.st post 1.sup.st post 1.sup.st post 1.sup.st post 1st MM
C-017 27 F Right BMI 37 37 37 37 Lost to Circumference 74 74 74 74
Follow up (cm) Area (cm) 14 .times. 14 0 1 .times. 10 6 .times. 3
Quadrants 4 0 2 1
[0038] Significant improvement in the reduction of cellulite of the
posterolateral thigh were seem in the patients who received
collagenase injection(s). This study has shown that collagenase
injection of areas of cellulite is a safe and effective method.
[0039] While this invention has been particularly shown and
described with reference to preferred embodiments thereof, it will
be understood by those skilled in the art that various changes in
form and details may be made therein without departing from the
scope of the invention encompassed by the appended claims.
* * * * *