U.S. patent application number 12/167720 was filed with the patent office on 2008-10-30 for method and apparatus for treating wrinkles in skin using radiation.
Invention is credited to R. Rox Anderson, James C. Hsia, Kathleen McMillan, Edward Victor Ross.
Application Number | 20080269733 12/167720 |
Document ID | / |
Family ID | 25163957 |
Filed Date | 2008-10-30 |
United States Patent
Application |
20080269733 |
Kind Code |
A1 |
Anderson; R. Rox ; et
al. |
October 30, 2008 |
METHOD AND APPARATUS FOR TREATING WRINKLES IN SKIN USING
RADIATION
Abstract
A method for treating wrinkles in skin involves the use of a
beam of pulsed, scanned or gated continuous wave laser or
incoherent radiation. The method comprises generating a beam of
radiation, directing the beam of radiation to a targeted dermal
region between 100 microns and 1.2 millimeters below a wrinkle in
the skin, and thermally injuring collagen in the targeted dermal
region. The beam of radiation has a wavelength of between 1.3 and
1.8 microns. The method may include cooling an area of the skin
above the targeted dermal region while partially denaturing the
collagen in the targeted dermal region. The method may also include
cooling an area of the skin above the targeted dermal region prior
to thermally injuring collagen in the targeted dermal region.
Inventors: |
Anderson; R. Rox;
(Lexington, MA) ; Ross; Edward Victor; (San Diego,
CA) ; Hsia; James C.; (Weston, MA) ; McMillan;
Kathleen; (Concord, MA) |
Correspondence
Address: |
PROSKAUER ROSE LLP
ONE INTERNATIONAL PLACE
BOSTON
MA
02110
US
|
Family ID: |
25163957 |
Appl. No.: |
12/167720 |
Filed: |
July 3, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10698970 |
Oct 31, 2003 |
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12167720 |
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09587156 |
Jun 5, 2000 |
6659999 |
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10698970 |
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09153052 |
Sep 15, 1998 |
6120497 |
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09587156 |
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08794876 |
Feb 5, 1997 |
5810801 |
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09153052 |
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Current U.S.
Class: |
606/9 |
Current CPC
Class: |
A61B 2018/0047 20130101;
A61N 2005/067 20130101; A61B 2018/00029 20130101; A61B 18/203
20130101; A61B 2018/00452 20130101; A61B 2017/00761 20130101; A61B
2018/00023 20130101 |
Class at
Publication: |
606/9 |
International
Class: |
A61B 18/28 20060101
A61B018/28 |
Claims
1-15. (canceled)
16. An apparatus for treating a wrinkle in human skin, comprising:
a source generating a beam of radiation having a wavelength within
a range at which a tissue absorption coefficient is in the range of
between 1 and 20 cm.sup.-1; a delivery system coupled to the source
for directing the beam of radiation to a targeted dermal region to
cause thermal injury sufficient to elicit a healing response that
produces substantially unwrinkled skin; and a cooling system for
cooling an epidermal region of the skin above the targeted dermal
region, to thereby minimize injury to the epidermal region.
17. The apparatus of claim 16 wherein the beam of radiation has a
fluence of between 10 and 150 joules per square centimeter.
18. The apparatus of claim 16 wherein the beam of radiation has a
power density of between 5 and 100 watts per square centimeter.
19. The apparatus of claim 16 wherein the beam of radiation has a
wavelength of between about 1.3 and 1.8 microns.
20. The apparatus of claim 16 wherein the beam of radiation is
directed to a targeted dermal region between 100 microns and 1.2
millimeters below a wrinkle in the skin.
21. The apparatus of claim 16 wherein the cooling system comprises
a container of cold fluid, wherein the cold fluid can be sprayed
onto the skin to extract heat from the skin on contact.
22. The apparatus of claim 16 wherein the cooling system further
comprises a skin contacting portion having a first end in optical
communication with a fiber coupled to the source and a second end,
the skin contacting portion projecting the beam of radiation to the
targeted dermal region through second end of the skin contacting
portion.
23. The apparatus of claim 16 wherein: the skin contacting portion
further comprises a window located at the second end of the skin
contacting portion, the window being in optical communication with
the fiber; and the skin contacting portion includes a fluid passage
extending across at least a portion of the window, the fluid
passage circulating a cooling fluid across the window.
24. An apparatus for treating a wrinkle in human skin, comprising:
a source generating a beam of radiation having a wavelength within
a range at which a tissue absorption coefficient is in the range of
between 1 and 20 cm.sup.-1; a delivery system coupled to the source
for directing the beam of radiation to a targeted dermal region
between 100 microns and 1.2 millimeters below a wrinkle in the
skin, wherein the beam of radiation causes thermal injury to the
targeted dermal region sufficient to elicit a healing response that
produces substantially unwrinkled skin; and a cooling system for
contact cooling an epidermal region of the skin above the targeted
dermal region, to thereby minimize injury to the epidermal
region.
25. The apparatus of claim 24 wherein the beam of radiation has a
fluence of between 10 and 150 joules per square centimeter.
26. The apparatus of claim 24 wherein the beam of radiation has a
power density of between 5 and 100 watts per square centimeter.
27. The apparatus of claim 24 wherein the beam of radiation has a
wavelength of between about 1.3 and 1.8 microns.
28. The apparatus of claim 24 wherein the delivery system further
comprises a fiber coupled to the source, the fiber carrying the
beam of radiation; and wherein the cooling system further comprises
a skin contacting portion having a first end in optical
communication with the fiber and a second end, the skin contacting
portion projecting the beam of radiation toward the targeted dermal
region through the second end of the skin contacting portion.
29. The apparatus of claim 28 wherein the skin contacting portion
further comprises a window located at the second end of the skin
contacting portion, the window being in optical communication with
the fiber; and wherein the skin contacting portion has a fluid
passage extending across at least a portion of the window, the
fluid passage circulating a cooling fluid past the window.
30. An apparatus for treating a wrinkle in human skin, comprising:
means for generating a beam of radiation having a wavelength of
between about 1.3 and 1.8 microns or having a wavelength within a
range at which a tissue absorption coefficient is in the range of
between 1 and 20 cm.sup.-1; means for directing the beam of
radiation to a targeted dermal region to cause thermal injury
sufficient to elicit a healing response that produces substantially
unwrinkled skin; and means for cooling an epidermal region of the
skin above the targeted dermal region, to thereby minimize injury
to the epidermal region.
Description
FIELD OF THE INVENTION
[0001] The invention relates generally to the treatment of wrinkles
in human skin using radiation. In particular, the invention relates
to a method for treating wrinkles in human skin using a beam of
laser or incoherent radiation to cause thermal injury in the dermal
region of the skin sufficient to elicit a healing response that
produces substantially unwrinkled skin.
BACKGROUND OF THE INVENTION
[0002] Undesired wrinkles in skin are commonly seen in dermatologic
practice. Wrinkles in skin may be caused by age and by exposure to
the sun's ultraviolet rays. Human skin consists mainly of two
layers: the top layer of skin known as the epidermis; and the layer
beneath the epidermis known as the dermis. The dermis is primarily
acellular and is composed of water, the protein collagen, and
glycosaminoglycans. Water constitutes approximately 70 percent of
the total weight of the dermis. Collagen constitutes approximately
70 percent of the dry weight of the dermis, and glycosaminoglycans
constitute between approximately 0.1 and 0.3 percent of the dry
weight of the dermis. Collagen and glycosaminoglycans are
constantly produced by fibroblasts, a type of connective tissue
cell, and degraded by enzymes. Collagen degradation relies
primarily on specific proteinases known as collagenases.
[0003] Collagen provides the dermis with the majority of its
structural integrity. With aging, the amount of dermal collagen
decreases and is replaced by the protein elastin. In addition, the
remaining collagen tends to be chaotically oriented as compared to
the more organized patterns found in youthful skin.
Glycosaminoglycans are very hydrophilic, and increased amounts of
these carbohydrates are associated with the increased skin vigor
found in youthful skin. One major difference between the smooth,
supple skin of newborns and the drier, thinned skin of older
individuals is the far greater relative amount of
glycosaminoglycans found in newborn skin. The glycosaminoglycans
found in newborns can bind up to 1000 times their weight in water.
As the skin ages and the amount of glycosaminoglycans decreases,
the skin may become less hydrated and lose some of the suppleness
found in youth. Also, the remaining glycosaminoglycans in
photo-aged skin are deposited on the haphazardly arranged elastin
fibers which have replaced the collagen fibers. The placement of
the remaining glycosaminoglycans may partially account for the
weather-beaten appearance of photo-aged skin.
[0004] Existing procedures for eliminating or reducing the severity
of wrinkles include chemical peels, mechanical abrasion and laser
ablation. All of these methods remove the top layer of skin. A new
top layer forms during healing. Cosmetic improvement is seen when
the skin containing wrinkles is replaced by a new layer of
horizontally oriented neocollagen in the superficial dermis.
However, all of these methods disrupt and completely remove the
epidermis. The resulting open wounds require daily care to optimize
wound healing. Epidermal destruction and subsequent healing has
several undesirable side effects. These undesirable side effects
include prolonged hypopigmentation, hyperpigmentation, erythema and
edema. Hyperpigmentation occurs frequently in darker skin types as
a result of an inflammatory response of the skin. Hyperpigmentation
results in the treated area of the subject's skin turning darker
than the surrounding untreated skin. Hyperpigmentation can be slow
to clear, sometimes taking up to a year to disappear.
Hypopigmentation is attributable to damage to the melanin-producing
cells in the skin. While generally transient, hypopigmentation can
be permanent, and is cosmetically undesirable while it persists.
Also, erythema or redness of the skin may be significant for weeks
to months after the procedure, requiring the patients to wear
conspicuous amounts of make-up.
[0005] A known property of collagen fibers, such as those found in
the skin, is that the fibers shrink when elevated to a temperature
in the range of 60 to 70 degrees Celsius, which is about 30 degrees
Celsius above normal body temperature. Temperature elevation
ruptures the collagen ultrastructural stabilizing cross-links, and
results in immediate contraction in the collagen fibers to about
one-third of their original length without changing the structural
integrity of the fibers. One known technique shrinks the collagen
fibers in the cornea of the eye to change the shape of the cornea
and correct refractive disorders. This technique involves the use
of laser energy in a wavelength range of about 1.80 to about 2.55
microns. The laser energy is used to irradiate the collagen in the
cornea to elevate the collagen to at least 23 degrees Celsius above
normal body temperature and thereby achieve collagen shrinkage.
U.S. Pat. Nos. 4,976,709, 5,137,530, 5,304,169, 5,374,265, and
5,484,432 to Sand disclose a technique and apparatus for controlled
thermal shrinkage of collagen fibers in the cornea.
[0006] However, this technique cannot be effectively used to remove
wrinkles in skin by shrinking dermal collagen. The bulk of the
shrunken, thermally denatured, collagen fibers do not remain in the
skin after treatment with this technique. Unlike the cornea, which
is avascular, an aggressive healing response in the skin degrades
the denatured collagen in the superficial dermis by collagenases,
thereby rapidly eliminating the bulk of the shrunken collagen from
the skin.
[0007] Additionally, in the 1.80 to 2.55 micron wavelength range,
strong absorption of the laser energy by water present in the skin
limits the penetration depth of the laser radiation to a small
fraction of a millimeter. The depths of thermal injury which can be
achieved in skin using the wavelengths in this range are therefore
limited to the most superficial layer of the skin. Such superficial
injury leads to an inflammatory healing response characterized by
prolonged visible edema and erythema, as well as the possibility
for long lasting pigmentary disturbances.
SUMMARY OF THE INVENTION
[0008] The present invention addresses the foregoing problems and
provides a method for inducing remodeling of the skin's
extracellular matrix by partially denaturing the dermal collagen
deeper in the skin, below the surface, while avoiding injury to the
epidermis and upper layers of the dermis. The invention offers
numerous advantages over existing dermatologic procedures and
devices. The surface of the skin remains intact, thereby avoiding
the need for dressing wounds; pigmentary disturbances are
minimized; and any inflammatory response to the injury is mild and
less visually evident.
[0009] In general, the present invention features a method for
treating wrinkles in skin, without removing a layer of skin, using
a beam of pulsed, scanned or gated continuous wave (CW) laser or
incoherent radiation. The method comprises generating a beam of
radiation having a wavelength between 1.3 and 1.8 microns,
directing the beam of radiation to a targeted dermal region between
100 microns and 1.2 millimeters below a wrinkle in the skin, and
thermally injuring the targeted dermal region to elicit a healing
response that produces substantially less wrinkles.
[0010] More specifically, causing selective thermal injury to the
dermis activates fibroblasts which deposit increased amounts of
extracellular matrix constituents (i.e., collagen and
glycosaminoglycans). These increases in extracellular matrix
constituents are responsible for dermal skin rejuvenation and the
reduced appearance of wrinkles.
[0011] In one embodiment, the beam of radiation causes partial
denaturation of the collagen in the targeted dermal region. The
partial denaturation of the collagen accelerates the collagen
synthesis process by the fibroblasts and the deposition of new
glycosaminoglycans, leading to the elimination or a reduction in
the severity of the wrinkle. The method may also include cooling
the surface of the skin and epidermal tissue above the targeted
dermal region while irradiating the skin. The method may also
include cooling the surface of the skin prior to irradiating the
skin.
[0012] In a detailed embodiment, the method also includes
stretching the skin along the wrinkle before directing the beam of
radiation to the targeted dermal region below the wrinkle.
Stretching the skin causes thermal injury to the collagen fibers
across the wrinkle, while not affecting the fibers along the
wrinkle.
[0013] The invention also relates to an apparatus for treating
wrinkles in skin. The apparatus includes a radiation source and a
delivery system which includes a cooling system. The radiation
source generates a beam of radiation having a wavelength between
1.3 and 1.8 microns. The delivery system directs the beam of
radiation to a targeted dermal region between 100 microns and 1.2
millimeters below a wrinkle in the skin. The cooling system cools
the epidermal tissue above the targeted dermal region to minimize
injury to the surface of the skin.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] The foregoing and other objects, features and advantages of
the invention will become apparent from the following more
particular description of preferred embodiments of the invention,
as illustrated in the accompanying drawings. The drawings are not
necessarily to scale, emphasis instead being placed on illustrating
the principles of the present invention.
[0015] FIG. 1 is an illustration of an apparatus including a
radiation source and a delivery system for practicing the
invention.
[0016] FIG. 2 is an enlarged perspective view of a delivery system
incorporating the principles of the invention.
[0017] FIG. 3 is an illustration of a wrinkle in skin exposed to a
plurality of radiation pulses.
[0018] FIG. 4 is an illustration of a region of skin exposed to a
highly convergent beam of radiation.
DETAILED DESCRIPTION OF THE INVENTION
[0019] The present invention contemplates a system and method for
removing wrinkles which includes delivering a beam of laser or
incoherent radiation to cause sufficient thermal injury in the
dermal region of the skin to elicit a healing response to cause the
skin to remodel itself, resulting in more youthful looking (i.e.,
substantially unwrinkled) skin. In particular, thermal injury may
be in the form of partial denaturation of the collagen fibers in
the targeted dermal region of skin. In one embodiment, the
radiation beam has a set of parameter ranges carefully selected to
partially denature collagen in the dermis while protecting the
epidermis by surface cooling. As a result, a subject treated using
the method of the invention is able to have the appearance of
wrinkles lessened without damage to the epidermis.
[0020] FIG. 1 is an illustration of a system 10 for practicing the
invention. The system 10 includes a radiation source 12 and a
delivery system 13. A beam of radiation generated by the radiation
source 12 is directed to a target region of a subject's skin
including a wrinkle via the delivery system 13. In one embodiment,
the radiation source 12 is a laser. The laser may generate a beam
of pulsed, scanned or gated CW laser radiation. In another
embodiment, the radiation source 12 generates incoherent
radiation.
[0021] The beam of radiation is directed to a targeted dermal
region of skin between 100 microns and 1.2 millimeters below the
wrinkle. The parameter ranges for the beam have been specifically
selected to cause thermal injury to the dermis while avoiding
injury to the epidermis and upper layers of the dermis. In
particular, the wavelength of the radiation beam has been chosen to
maximize absorption in the targeted region of the dermis, and the
fluence or power density, depending on the type of radiation, has
been chosen to minimize erythema. The wavelength range chosen has a
tissue absorption coefficient preferably in the range of about 1 to
20 cm.sup.-1. Thus, the beam preferably has a wavelength of between
about 1.3 and 1.8 microns in one embodiment. Within this wavelength
range, radiation energy applied through the surface of the skin is
deposited predominantly in the dermal region of the skin. In one
embodiment, the radiation beam has a nominal wavelength of
approximately 1.5 microns. Lasers which produce radiation having
wavelengths in the range of between about 1.3 and 1.8 microns
include the 1.33 micron Nd:YAG laser, the 1.44 micron Nd:YAG laser
and the 1.54 micron Er:Glass laser. The radiation beam may be
pulsed, scanned or gated continuous wave laser radiation. In
embodiments having a laser as the radiation source 12, the laser
radiation generated preferably has a fluence of between about 10
and 150 joules.
[0022] In another embodiment, the radiation used to thermally
injure the dermis is incoherent radiation. In embodiments using
incoherent radiation, the incoherent radiation generated by the
radiation source 12 preferably has a power density of between about
5 and 100 watts per square centimeter.
[0023] FIG. 2 is an enlarged perspective view of a delivery system
13 incorporating the principles of the invention. The delivery
system 13 includes a fiber 14 having a circular cross-section and a
handpiece 16. A beam of radiation having a circular cross-section
is delivered by the fiber 14 to the handpiece 16. An optical system
within the handpiece 16 projects an output beam of radiation to a
targeted region of the subject's skin. A user holding the handpiece
16 irradiates the targeted region of the subject's skin including
the wrinkle with output pulses from the beam.
[0024] To minimize thermal injury to the epidermis and the upper
layers of the dermis, in one embodiment, the delivery system 13
includes a cooling system for cooling the surface of the skin prior
to and/or during application of the radiation. In this embodiment,
the delivery system 13 is multi-functional and is capable of
delivering radiation and cooling the surface of the skin at the
same time. FIG. 3 shows one embodiment of a delivery system 13
which includes a cooling system. The handpiece 16 includes a skin
contacting portion 20 which is brought into contact with the region
of skin 22 receiving the beam of radiation 24. The skin contacting
portion 20 cools the epidermal region of skin 22 receiving the beam
of radiation. The skin contacting portion 20 includes a sapphire
window 26 and a fluid passage 28 which contains a cooling fluid.
The cooling fluid may be a fluorocarbon type cooling fluid. The
cooling fluid circulates through the fluid passage 28 and past the
sapphire window 26 which is in contact with the epidermal region of
skin 22 receiving the beam of radiation 24.
[0025] In another embodiment, the delivery system 13 and the
cooling system are separate systems. The cooling system may
comprise a container of a cold fluid. Cooling of the surface of the
skin is accomplished by briefly spraying the skin with the cold
fluid which extracts heat from the skin on contact. The fluid used
can also be a non-toxic substance with high vapor pressure at
normal body temperature, such as a freon. These fluids extract heat
from the skin by the virtue of evaporative cooling.
[0026] FIG. 3 illustrates the treatment of a wrinkle 30 in
accordance with the invention. Radiation pulses are produced using
the radiation source 12, which may be a pulsed, scanned or gated CW
laser or incoherent radiation source. The radiation pulses are
directed toward the region 22 of the subject's skin containing the
wrinkle 30 by the delivery system 13. The radiation pulses are
preferably directed to a targeted dermal region between 100 microns
and 1.2 millimeters below the surface of the skin. In a detailed
embodiment, the radiation pulses are focused to a region centered
at a depth of about 750 microns. The targeted dermal region
including a portion of the wrinkle 30 is then irradiated with
radiation pulses exiting from the handpiece 16 until collagen in
that region is partially denatured. To accomplish this, the
collagen at the selected depth in the targeted dermal region is
preferably heated to a temperature in the range of about 50 to 70
degrees Celsius. Partially denaturing collagen in the dermis
accelerates the collagen synthesis process by the fibroblasts. The
thermal injury caused by the radiation is mild and is only
sufficient to elicit a healing response and cause the fibroblasts
to produce new collagen. Excessive denaturation of collagen in the
dermis causes prolonged edema, erythema, and potentially
scarring.
[0027] The skin contacting portion 20 preferably cools the area of
the skin above the targeted dermal region to temperatures below
approximately 50 to 70 degrees Celsius during application of the
radiation, so as not to cause collateral thermal damage to the
epidermis. The radiation beam, due to its wavelength, does not
sufficiently penetrate into depths below the targeted dermal region
to cause thermal damage deeper in the skin. In one detailed
embodiment, the skin contacting portion 20 cools an area of the
skin above the targeted dermal region before the radiation is
applied. The relative timing of cooling the surface of the skin to
applying radiation depends, in part, on the depth to which thermal
injury is to be prevented. Longer periods of cooling prior to the
application of radiation allow more time for heat to diffuse out of
the skin and cause a thicker layer of skin to be cooled, as
compared to the thickness of the layer cooled by a short period of
cooling. This thicker layer of cooled tissue sustains less thermal
injury when the radiation energy is subsequently applied. Continued
cooling of the surface of the skin during the delivery of radiation
energy extracts heat from the upper layers of the skin as heat is
deposited by the radiation, thereby further protecting the upper
layers from thermal injury.
[0028] The depth of thermal injury caused by the radiation depends
primarily on the penetration depth of the radiation used. The
penetration depth can be approximated by taking the reciprocal of
the absorption coefficient of the skin at the wavelength of the
radiation. The thickness of the tissue overlying the zone of injury
which is spared from injury depends primarily on the cooling
applied prior to and/or during the delivery of radiation energy. By
suitably choosing the radiation wavelength, the timing of the
surface cooling, the cooling temperature, the radiation fluence
and/or the power density as described above, the depth, the
thickness and the degree of thermal injury can be confined to a
zone within the dermis. These parameters can be chosen to optimally
induce the injury required to elicit remodeling within the dermis,
while substantially or completely sparing injury to the overlying
epidermis and upper layers of the dermis.
[0029] In another detailed embodiment, the region of skin including
the wrinkle 30 is stretched along the wrinkle 30 before the beam of
radiation is directed to the targeted dermal region below the
wrinkle 30. Stretching the skin along the wrinkle before
irradiating the skin causes partial denaturation of the collagen
fibers across the wrinkle, while not damaging the fibers along the
wrinkle. Partially denaturing the fibers across the wrinkle
tightens the skin sufficiently to cause the wrinkle to
disappear.
[0030] Referring to FIG. 4, in one embodiment, to counteract the
effects of scattering, the radiation beam is made highly convergent
on the surface of the skin.
Experimental Results
[0031] The method of the present invention for treating wrinkles in
skin using radiation was applied in a series of in vivo experiments
performed on pigs. A pulsed erbium glass laser producing radiation
having a wavelength of approximately 1.54 microns was used as the
radiation source 12. The laser energy was applied to the pig skin
via the skin contacting portion 20 equipped with a cooled sapphire
window 26 at the tip, as described above and shown in FIGS. 1-3.
The inner surface of the sapphire window 26 was cooled by
circulating refrigerated coolant, chilled to approximately minus 25
degrees Celsius through the passage 28. The coolant used was a
halocarbon which is transparent to the 1.54 micron laser radiation.
The laser beam at the outer surface of the sapphire window 26 was
approximately 5 mm in diameter.
[0032] The tip of the skin contacting portion 20 was placed in
contact with the skin to cool the skin prior to applying the laser
radiation. After a set amount of time (hereinafter "the pre-cooling
time"), laser energy was applied to the skin. Various combinations
of pre-cooling times, laser pulse energies, laser pulse repetition
frequencies, time intervals of laser energy delivery, and total
number of laser pulses delivered were studied. It was found that by
the appropriate choice of these parameters, varying degrees of
thermal injury can be achieved at varying depths in the dermis
while preserving the viability of the epidermis and upper
dermis.
[0033] For example, using a pre-cooling time of 5 seconds, a laser
energy in the range of between 0.2 and 0.8 joules per pulse at a
pulse repetition frequency of 4 Hertz (corresponding to an average
laser power in the range between 0.8 to 3.2 watts), and a total of
24 pulses, it was found that varying degrees of thermal injury
could be induced in a zone centered at a depth in the range of
approximately 0.5 to 1.0 millimeters beneath the surface of the
skin, while avoiding injury to the epidermis and upper dermis.
[0034] Histology performed on biopsy samples taken at sites treated
with the above range of parameters revealed collagen denaturation
extending from about 100 microns in the dermis to about 1 mm deep.
The epidermis and upper layers of the dermis were preserved as
confirmed with nitrotetrazolium blue, a viability stain. In the
cases in which only partial collagen denaturation was shown on
histology, clinically, the treated areas showed an intact epidermis
with mild edema and erythema which resolved completely within two
weeks. Histologically, the treated sites showed greatly increased
fibroblast activity, new collagen secretion and degradation of
denatured collagen. By four weeks post treatment, the treated sites
returned to normal, both clinically and histologically.
EQUIVALENTS
[0035] While the invention has been particularly shown and
described with reference to specific embodiments, it should be
understood by those skilled in the art that various changes in form
and detail may be made therein without departing from the spirit
and scope of the invention as defined by the appended claims.
* * * * *