U.S. patent application number 11/202014 was filed with the patent office on 2006-06-15 for method of treating acne.
This patent application is currently assigned to Cynosure, Inc.. Invention is credited to Jennifer R. Lloyd, Mirko Mirkov.
Application Number | 20060128771 11/202014 |
Document ID | / |
Family ID | 25449789 |
Filed Date | 2006-06-15 |
United States Patent
Application |
20060128771 |
Kind Code |
A1 |
Mirkov; Mirko ; et
al. |
June 15, 2006 |
Method of treating acne
Abstract
A method of selectively enhancing photothermal sebaceous gland
disruption and treatment of acne is disclosed. The method provides
for alleviation of the acne symptoms as well as preventing acne
recurrence and new acne from occurring.
Inventors: |
Mirkov; Mirko; (Chelmsford,
MA) ; Lloyd; Jennifer R.; (Poland, OH) |
Correspondence
Address: |
BANNER & WITCOFF, LTD.
28 STATE STREET
28th FLOOR
BOSTON
MA
02109-9601
US
|
Assignee: |
Cynosure, Inc.
Chelmsford
MA
|
Family ID: |
25449789 |
Appl. No.: |
11/202014 |
Filed: |
August 11, 2005 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
09924156 |
Aug 7, 2001 |
7018396 |
|
|
11202014 |
Aug 11, 2005 |
|
|
|
Current U.S.
Class: |
514/369 ;
514/414; 604/20; 607/86 |
Current CPC
Class: |
A61N 5/0616 20130101;
A61N 2005/067 20130101; A61N 5/062 20130101; A61B 18/203 20130101;
A61B 2018/00452 20130101 |
Class at
Publication: |
514/369 ;
514/414; 604/020; 607/086 |
International
Class: |
A61K 31/427 20060101
A61K031/427; A61K 31/405 20060101 A61K031/405; A61N 1/30 20060101
A61N001/30 |
Claims
1-14. (canceled)
15. A method of treating a patient who has an unwanted skin
condition associated with the production of sebum, the method
comprising: generating, on the patient's skin, a target region
having substantially clear pores, wherein generating the target
region comprises applying an acidic composition to an area of the
patient's skin and heating or mechanically abrading the area;
topically administering an exogenous chromophore onto the target
region, wherein the chromophore absorbs laser light having a
wavelength between about 700 nm to about 1200 nm; and irradiating
the target region with laser light having a wavelength between
about 700 nm to about 1200 nm for a time sufficient to inhibit
subsequent sebum production.
16. The method of claim 15, wherein applying an acidic composition
to an area of the patient's skin comprises topically applying a
glycolic acid solution or a salicylic acid preparation to the
area.
17. The method of claim 16, wherein the acidic solution is a
blycolic acid solution and the method further comprises the step of
neutralizing the glycolic acid solution by administering at least
one neutralizing agent.
18. The method of claim 17, wherein the neutralizing agent is
water, a sodium bicarbonate solution, or GLYTONE.RTM..
19. The method of claim 15, wherein the glycolic acid solution is a
70% glycolic acid solution.
20. The method of claim 15, further comprising, prior to the step
of generating the target region, a step of wiping an area of the
patient's skin with alcohol, wherein the area subject to wiping is
substantially the same as the target region.
21. The method of claim 15, wherein the unwanted skin condition is
acne.
22. The method of claim 15, wherein the chromophore is a lipophilic
chromophore.
23. The method of claim 22, wherein the lipophilic chromophore is
beta-carotene.
24. The method of claim 15, wherein the chromophore is a dye.
25. The method of claim 24, wherein the dye is indocyanine green,
Rhodamine B, or cresyl violet.
26. The method of claim 15, wherein the chromophore is combined
with a lipophilic carrier.
27. The method of claim 26, wherein the lipophilic carrier is a
liposome.
28. The method of claim 26, wherein the lipophilic carrier is a
lipid suspension.
29. The method of claim 28, wherein the lipid suspension comprises
an oil or a surfactant.
30. The method of claim 29, wherein the oil is a sunflower oil, an
olive oil, or a safflower oil.
31. The method of claim 15, wherein the wavelength is between abut
750 nm and about 850 nm.
32. The method of claim 15, wherein the wavelength is between about
800 nm and about 820 nm.
33. The method of claim 15, wherein irradiating the target region
with laser light comprises irradiating the target region with laser
light having a pulse duration of about 200 msec.
34. The method of claim 15, wherein irradiating the target region
with laser light comprises irradiating the target region with laser
light having a pulse duration of about 500 msec.
Description
RELATED U.S. APPLICATION(S)
[0001] This application claims priority from U.S. patent
application Ser. No. 09/924,156, filed Aug. 7, 2001, which is
hereby incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] Embodiments of the present invention relate in general to
the combined use of laser therapy and laser light absorbing agents
in the treatment of skin conditions associated with the production
of sebum by sebaceous glands. More particularly, embodiments of the
present invention relate to methods of preventing, reducing,
eliminating, or otherwise treating unwanted skin conditions, such
as acne, using laser light and one or more exogenous chromophores
to disrupt production of sebum without significant harm to
surrounding normal tissue.
[0004] 2. Description of Related Art
[0005] Unwanted skin conditions associated with the production or
overproduction of sebum are well known. One example of such an
unwanted skin condition includes common acne which is a major
treatment concern of many dermatologists. It is estimated that as
many as 32 million Americans exhibit some form of unwanted
acne.
[0006] The treatment of acne is of major concern to dermatologists.
Acne accounts for more than four million visits to dermatologists
each year. Typically, acne arises in the early teen years and
subsides by the mid twenties. In many cases, particularly in women,
acne remains a chronic problem well into the adult years. It is
estimated that as many as 32 million Americans suffer from
acne.
[0007] Acne vulgaris, the most common form of acne, is the result
of the secretion of sebum by the sebaceous gland into a blocked
pore. Continued secretion results in buildup of the sebum in the
blocked pore. Bacteria in the pore gives rise to infection and a
common unsightly skin condition known as pimples. Sebaceous gland
hyperplasia is also a common form of acne in which the sebaceous
gland grows or become enlarged as a result of overproduction of
sebum. A pimple is formed even if the gland is not blocked.
[0008] Sebaceous glands and the sebum they produce apparently have
no commonly accepted significant function in humans. The skin of
young children does not appear to be negatively affected by the
almost total lack of sebum. The only known role of sebum in humans
is in the pathogenesis of acne. In the past, physicians treated
acne with radiation therapy to destroy the sebaceous gland.
Radiation, however, does not specifically target the sebaceous
glands, and can cause significant morbidity to normal tissue
because of its mutagenic toxicity. Increased risk of cutaneous
carcinoma has also been associated with radiation therapy. Current
acne treatments do not eradicate the sebaceous glands selectively
and without harm to surrounding normal tissue, and therefore remain
non-curative and inadequate. The result is years of chronic therapy
and potential scarring for the patient.
[0009] Selective photothermolysis is a method of causing selective
and irreversible photothermal damage to tissue structures
containing a chromophore that can be used to distinguish that
target structure from surrounding tissue. For a light source,
typically a laser, to be useful for selective photothermolysis, it
must emit with sufficient intensity at a wavelength preferentially
absorbed by the target chromophore. The pulse duration or exposure
time of the source must be less than the thermal relaxation time of
the target to minimize temperature increases in tissue surrounding
the target. Techniques based on this concept using well known laser
systems are well established for treatment of benign cutaneous
vascular lesions such as portwine stain (PWS), birthmarks,
telangiectasias, hemangiomas, warts, psoriasis, arthritis in which
hemoglobin in the abnormal ectatic lesional vasculature serves as
the chromophore and the target is the vessel wall, as well as,
atherosclerotic plaque and other desired applications. See U.S.
Pat. No. 5,312,395; U.S. Pat. No. 5,749,868; U.S. Pat. No.
5,257,970; U.S. Pat. No. 5,066,293, U.S. Pat. No. 5,346,488,
"Selective Photothermolysis: Precise Microsurgery by Selective
Absorption of Pulsed Radiation", Anderson et al., Science,
220:524-527 (1983); Spears et al. J. Clin. Invest, 71, 39-399
(1983), the disclosure of each of which is hereby incorporated by
reference in their entireties for all purposes. The deepest blood
vessels contributing to the color of PWS lesions are approximately
1 mm below the skin surface, and are accessible to selective
photothermal targeting using available lasers such as the 585 nm
pulsed dye laser. The theoretical advantages of selective
photothermolysis have been borne out in clinical studies showing
that PDL (pulsed dye laser) treatment of benign cutaneous vascular
lesions is associated with very low risk of scarring. However,
photothermolysis techniques involving the direction of laser light
onto the surface of skin would be more effective if the laser light
was not substantially absorbed by components of skin and
particularly if an exogenous chromophore was used which selectively
collected in the targeted tissue and which absorbed laser light at
a wavelength substantially outside that absorbed by normal skin
components.
[0010] One approach to the treatment of acne is to reduce the
production of sebum by disrupting or even destroying the sebaceous
gland. One such method described in U.S. Pat. No. 5,817,089
includes forcing, for example by the use of ultrasound, an
exogenous chromophore into spaces within or adjacent sebaceous
glands. The chromophore is then illuminated with short pulses of
laser light so as to provide sufficient energy to the chromophore
to create explosions which blow off layers of dead skin cells
and/or destroy tissue responsible for hair growth and/or sebum
production.
[0011] The use of beta-carotene as an exogenous chromophore along
with lasers to treat acne is considered in U.S. Pat. No. 5,304,170.
However, the laser light has a wavelength between 425 nm and 550 nm
which suffers from poor penetration within the tissues. Further,
while beta-carotene does collect in sebaceous glands, it also
collects in the tissue between the glands and surrounding tissue
and skin components, resulting in poor selectivity and yellowing of
the skin.
[0012] Efforts to use lasers to treat certain skin conditions and
to effect hair removal include Manuskiatti et al., J. Am. Acad.
Dermatol., vol. 41, Number 2, Part 1, pp. 176-180 (1999),
Friedlander, Pediatric Dermatology, vol. 15, No. 5, pp. 396-398
(1998), Shuster, Acta Dermatovener (Stockh) Suppl., 120, pp. 43-46,
Sigurdsson et al., Dermatology, 194, pp. 256-260 (1997), Sumian et
al., J. Am. Acad. Dermatol., Vol. 41, Number 2, Part 1, pp. 172-175
(1999), the disclosure of each of which is hereby incorporated by
reference in their entireties for all purposes. However, these
efforts do not recognize the use of laser light having a wavelength
outside that significantly absorbed by skin or skin components or
the use of an exogenous chromophore which can be selectively
introduced to sebaceous glands.
[0013] Accordingly, there is a need in the art to provide methods
of treating unwanted skin conditions associated with sebum
production or overproduction which employ laser light having a
wavelength outside that substantially absorbed by skin or skin
components. There is also a further need in the art to selectively
localize the effects of photothermolysis to sebaceous glands using
a chromophore which absorbs laser light having a wavelength outside
that substantially absorbed by skin or skin components and further
without significantly harming surrounding normal tissue. There is a
further need to develop methods for introducing an exogenous
chromophore into sebaceous glands where such chromophore would
normally lack affinity for sebaceous gland material.
BRIEF SUMMARY OF THE INVENTION
[0014] Embodiments of the present invention are directed to methods
in humans which are useful in treating skin conditions associated
with the production or overproduction of sebum by sebaceous glands.
Sebaceous glands are treated according to one method of the present
invention in a manner to reduce or prevent the production of sebum
without significantly harming or otherwise adversely affecting
surrounding normal tissue. Methods of the present invention also
include treating unwanted skin conditions associated with sebum
production, such as acne. According to the present invention, the
production of sebum is reduced in a manner to reduce, prevent or
eliminate the occurrence or reoccurrence of unwanted skin
conditions, such as acne.
[0015] According to one embodiment of the present invention, a
chromophore, such as a dye, is administered to the site of
irradiation. The term "chromophore" also includes compounds having
chromophoric groups such as nitro groups, azo, alkylene units,
esters, carbonyl groups, aldehydes, alkynes, aromatic rings,
heterocyclics, carboxylic acids and the like. The chromophore acts
to selectively absorb the chosen wavelength of laser light thereby
enhancing the effectiveness of the irradiation. Other chromophores
or photoactive or photoabsorbable compounds can be used which
themselves act as therapeutic or cytotoxic agents upon irradiation.
According to the methods of the present invention, an exogenous
chromophore is selectively introduced into a holocrine gland, such
as a sebaceous gland, selected for treatment. The exogenous
chromophore preferably absorbs laser light having a wavelength
significantly outside the wavelengths absorbed by skin or skin
components. According to one embodiment, an otherwise lipophobic
exogenous chromophore is rendered substantially lipophilic so as to
be selectively introduced into sebaceous glands. The sebaceous
glands having the chromophores introduced therein are then
irradiated with laser light having a wavelength, duration, fluence
and spot size selected to preferentially heat the sebaceous glands
in a manner to disrupt, reduce, eliminate or otherwise interfere
with the production of sebum. According to one embodiment, the
sebaceous glands are heated to the point of denaturation and to
effectively prevent the production of sebum that is required for
the development or continued presence of unwanted skin conditions
such as acne.
[0016] Other features and advantages of certain embodiments of the
present invention will become more fully apparent from the
following description taken in conjunction with the accompanying
figures and claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] In the course of the detailed description of certain
preferred embodiments to follow, reference will be made to the
attached figures, in which,
[0018] FIG. 1 is a photomicrograph showing tissue containing
sebaceous glands viewed under normal illumination with white light
wherein the tissue has been treated with a topical administration
of indocyanine green which has been rendered lipophilic.
[0019] FIG. 2 is a photomicrograph of the same tissue shown in FIG.
1 but illuminated at 810 nm and observed through an 840 nm bandpass
filter. FIG. 2 shows that indocyanine green is present in the
sebaceous glands but not in the tissue between the glands.
[0020] FIG. 3 is a sample of human skin treated with an indocyanine
green microemulsion for 24 hours before excision.
[0021] FIGS. 4A and 4B are histological studies from a human
volunteer with active acne.
[0022] FIGS. 5A-5D are photographs showing a reduction in acne
after treatment using the invention described here.
DETAILED DESCRIPTION OF CERTAIN PREFERRED EMBODIMENTS
[0023] The principles of the present invention may be applied with
particular advantage to treat unwanted skin conditions or disorders
associated with the production or overproduction of sebum by
sebaceous glands. According to the teachings of the present
invention, sebaceous glands or other components of the
pilosebaceous unit such as the infundibulum opening are altered,
modified or disrupted by selectively introducing one or more
exogenous agents, dyes or chromophores to the sebaceous glands in
the affected area of skin to enhance the absorption of laser light
at a site of irradiation within the skin and to also aid in the
selective absorption of laser light. Exogenous chromophores or
compounds including chromophoric groups are administered to take
advantage of the deeper tissue penetration of longer visible or
near-infrared wavelengths. One or more photoactivated compounds can
also be administered as necessary to therapeutically treat the
affected area of the skin. The amount, duration and mode of
administration of the chromophore or other photoactive agent will
depend on its properties and the makeup of the individual on which
the treatment is to be carried out.
[0024] The affected area of skin is then irradiated with light
having a wavelength strongly absorbed by the chromophore. The light
has a wavelength, duration, fluence, and spot size sufficient to
result in heating of the chromophore in the sebaceous glands such
that the sebaceous glands are modified, altered, destroyed,
damaged, disrupted or otherwise rendered incapable of producing
sebum at excessive or normal levels. According to one embodiment,
the sebaceous glands are prevented from producing sebum necessary
to promote or sustain unwanted skin conditions such as acne. In
other embodiments, the sebaceous glands may be disrupted to
alleviate symptoms of medical conditions other than acne, e.g.
seborrheic dermatitis commonly seen in infants and in HIV
patients.
[0025] In one embodiment, the laser light is produced by a tunable
pulsed dye laser system or diode laser system and is characterized
as having a wavelength corresponding to that which is absorbed by
the selected chromophore. Preferably, the laser light also has a
wavelength that is substantially transmitted by the outer layers of
the skin, i.e., the first 1 to 2 millimeters of skin.
"Substantially transmitted" is used herein to indicate that not
less than 60% of the laser light is transmitted through the first 2
millimeters of skin, or alternatively, not less than 60% of the
laser light reaches target sebaceous glands. In general, suitable
pulsed dye laser systems useful in the present invention include a
power source, a flashlamp capable of emitting multiple pulses of
light, a dye reservoir containing a dye suitable for stimulated
emission of light, and an optical resonator having an output
coupler. The power source, flashlamp, dye reservoir and optical
resonator are operatively connected so as to generate multiple
pulses of laser light having a defined wavelength and pulse
duration. An optical fiber is optically coupled to the optical
resonator in a manner to allow the multiple pulses of laser light
to travel from the optical resonator through the optical fiber to
the tissue area to be irradiated with a defined pulse fluence. A
handpiece delivery system incorporating the terminal end of the
optical fiber is used to effectively direct the laser light source
to the target area.
[0026] In a second embodiment, light is produced by a tunable dye
system that emits light continuously. That is, light is emitted
continuously from the source. Preferably, the light has a
wavelength that is substantially transmitted by the outer layers of
skin. Suitable light system have a light source, such as an arc
lamp, a dye reservoir for selecting the wavelength of light emitted
from the system, a monochromator, and one or more shutters to
prevent passage of the light. The shutter can be opened and closed
using a pre-selected delay time to provide for pulsing of the
light. For example, the shutter can be opened for about 1 ms and
then closed for about 1 second to provide for a pulse duration of
about 1 ms with a delay time of about 1 second. An optical fiber is
optically coupled to the light system in a manner to allow the
multiple pulses of light to travel from the optical resonator
through the optical fiber to the tissue area to be irradiated with
a defined pulse fluence. A handpiece delivery system incorporating
the terminal end of the optical fiber is used to effectively direct
the light source to the target area.
[0027] According to one embodiment, useful wavelengths are between
about 700 nm and about 1200 nm, preferably between about 750 nm and
about 850 nm and more preferably between about 800 nm and about 820
nm. 810 nm is a particularly preferable wavelength since melanin,
the primary human skin pigment, does not absorb strongly at that
wavelength. Additionally, commonly used topical acne treatments,
such as Retin-A.RTM. (all-trans-retinoic acid), typically absorb
light at about 351 nm. Thus, acne patients may undergo the
treatment methods described here while continuing with other
topical acne treatments. The laser light has a pulse duration less
than the thermal relaxation time of the volume of tissue being
irradiated. Specific pulse durations include between 0.1 msec and
about 500 msec, preferably between about 1 msec and about 200 msec.
The delivered fluence of the pulsed laser light is between about 1
J/cm.sup.2 and about 50 J/cm.sup.2, preferably between about 5
J/cm.sup.2 and about 40 J/cm.sup.2 and more preferably about 10
J/cm.sup.2. The irradiated spot size is sufficient to include the
manifestation of the unwanted skin condition of interest as a whole
or portions thereof. According to an additional embodiment, the
spot size is sufficient to include not only the acne, but also an
area of normal tissue adjacent to or surrounding the acne to be
treated which may include sebaceous glands which have not yet
developed into visible acne, e.g. preferentially the entire
holocrine gland and surrounding tissue including other sebaceous
glands are treated. The area of visibly normal tissue adjacent to
or surrounding the acne to be treated is referred to herein as the
"margin" or "margin of tissue." Alternatively, the laser light has
a spot size sufficient to irradiate only the margin or portions
thereof, or part of the margin and part of the acne. Spot sizes in
accordance with the present invention include those between about 1
mm to about 20 mm, preferably about 5 mm to about 15 mm. Depending
upon the intended use and the size of the subject's sebaceous
glands, the spot size may be smaller, e.g. about 500 .mu.m to about
1 mm for use in infants, or larger, e.g. about 20 mm to about 30 mm
for use in adults having larger sebaceous glands. In preferred
embodiments, the spot size may be reduced during use by adjustment
of the optical fiber aperture, e.g. the spot size can be increased
or decreased during use.
[0028] According to the present invention, the area of the
individual to be treated should be irradiated at least once with
laser light having the above parameters, with the appropriate
number of pulses necessary to treat the entire area. The complete
treatment may be repeated up to five times with at least one week
between each treatment.
[0029] It is to be understood that other lasers, such as yellow,
green and blue wavelength lasers which produce laser light suitable
of being absorbed by an exogenous chromophore taken up by or
otherwise introduced into sebaceous glands, are useful within the
scope of the present invention and include Argon ion lasers,
Copper-vapor lasers, alexandrite lasers, ruby lasers, semiconductor
diode lasers, frequency-doubled Nd:YAG lasers, and other dye lasers
pumped by a Nitrogen laser or Argon-ion laser and the like. The
lasers and other light sources within the scope of the present
invention are preferably pulsed but may also operate in a
continuous-wave (cw) mode with a scanner to automatically scan the
treatment area and provide temporal modulation of the laser
intensity on the treatment site.
[0030] The advantage of the selective photothermal sebaceous gland
targeting over conventional methods of disrupting sebaceous gland
activity include the more efficient use of laser light should a
chromophore be used that absorbs at a wavelength substantially
transmitted by skin or skin components. In addition, such a
chromophore when rendered substantially lipophilic provides
selective loading of the chromophore into the sebaceous glands
versus surrounding tissue. This allows for a method of
discriminating between sebaceous glands as opposed to surrounding
tissue for purposes of absorption of laser light.
[0031] According to the invention, the sebaceous glands are
irradiated to the extent to cause irreversible damage to the
sebaceous glands but also in a manner to spare surrounding tissue,
e.g. the thermal damage to surrounding tissue is minimal. This
method is implemented, depending on the area of skin to be treated,
by means of the pulsed dye laser or any other source of radiation
preferentially absorbed by the exogenous chromophore selectively
introduced into sebaceous glands.
[0032] According to additional embodiments, the methods described
here may be used to treat skin conditions other than acne. For
example, lipophilic chromophores may be administered or disposed on
skin lesions. Because the rate of uptake of compounds by certain
skin lesions may be larger than the rate of uptake in normal
tissue, the skin lesions may be selectively destroyed using the
methods described here. That is, the concentration of chromophores
inside the skin lesion cells typically can be much larger than the
concentration inside normal cellular tissue. Therefore,
administration of light to the region of the skin lesions, destroys
the skin lesions while minimizing the amount of normal tissue
surrounding the skin lesions that is destroyed. Alternatively, the
skin lesion can be injected with a chromophore prior to irradiation
of the skin lesion.
[0033] The following examples are set forth as representative of
the present invention. These examples are not to be construed as
limiting the scope of the invention as these and other equivalent
embodiments will become apparent in view of the present disclosure,
figures and accompanying claims.
EXAMPLE I
Introduction of a Chromophore to Sebaceous Glands
[0034] The selective introduction of a chromophore to sebaceous
glands is accomplished by topically applying a selected chromophore
to the skin under conditions that permit the chromophore to
selectively localize to the sebaceous glands. The selective
introduction of a chromophore to sebaceous glands is most readily
accomplished using lipophilic chromophores, or alternatively, by
preparing less lipophilic chromophores in a carrier that renders
them more lipophilic.
[0035] Chromophores useful in the methods of the invention should
meet at least the following criteria. First, chromophores of use in
the methods of the invention must strongly absorb light at a
selected wavelength or portion of the spectrum. There are a large
number of chromophores known in the art that meet this criterion,
but particularly preferred among them are those that strongly
absorb light energy at a wavelength or portion of the spectrum that
is not strongly absorbed by natural skin pigments such as melanin,
which absorbs at between about 500 nm to 600 nm.
[0036] A second criterion for a chromophore useful in the methods
of the invention is that it be lipophilic, i.e., substantially
soluble in a fat or lipid. The lipophilic nature of the chromophore
facilitates the selective introduction of the chromophore to the
sebaceous gland. Lipophilic chromophores include, for example,
organic tissue stains and beta-carotene. Lipophilic chromophores
may be dissolved in an acceptable oil and then applied directly to
the area of skin one wishes to treat. Alternatively, the pores of
the skin may be opened using heat, steam and the like to facilitate
entry of the chomophores into the sebaceous glands.
[0037] It is recognized herein that a number of chromophores that
absorb light energy at a wavelength or portion of the spectrum that
is not absorbed by natural skin pigments, and thus might be
expected to be useful for the methods of the invention, are not
lipophilic. That is, there are a number of chromophores,
particularly organic dye molecules, that would be useful in the
methods of the invention except that they are not soluble in lipid
or fat. Such chromophores include indocyanine green, methylene blue
and other common dyes such as Rhodamine B and cresyl violet and the
like. See also other chromophores useful in the present invention
identified in U.S. Pat. No. 4,651,739, the disclosure of which is
hereby incorporated by reference in its entirety for all purposes.
The methods of the invention overcome this limitation by combining
such chromophores with a lipophilic carrier preparation. In this
way, the non-lipophilic chromophores are rendered lipophilic,
allowing their selective introduction to the sebaceous gland.
[0038] Finally, a chromophore useful in the methods of the
invention must be safe to apply to human skin. The chromophore must
not be toxic or carcinogenic in the amounts to be applied. Data
regarding toxicity and carcinogenicity of chemical compounds are
widely known in the art.
EXAMPLE II
Rendering Non-Lipophilic Chromophores Lipophilic
[0039] According to one aspect of the present invention,
non-lipophilic chromophores, for example, indocyanine green, are
rendered lipophilic by several possible methods, including the use
of liposomes and lipid suspensions. By associating a non-lipophilic
chromophore with a lipid in either a liposome or a lipid
suspension, the chromophore is selectively deposited within the
sebaceous glands.
[0040] Liposomes containing a non-lipophilic chromophore are
prepared using the following protocol. Appropriate amounts of the
lipids are mixed in a beaker and melted at 75.degree. C. The melt
is then drawn into a syringe preheated in a water-bath at
75.degree. C. A second syringe containing 0.05 M isotonic HEPES
buffer, pH 7.4, is preheated to 70.degree. C. The two syringes are
then connected via a 3-way Teflon or metal stopcock. The aqueous
buffer is then injected into the lipid phase syringe. The mixture
is mixed back and forth between the two syringes rapidly several
times while being cooled under cold tap water. This process is
continued until the mixture is at room temperature. The resulting
liposomal suspensions are then examined using a light microscope to
assure integrity and quality of the liposomal preparations. A
non-lipophilic chromophore may alternatively be prepared in a lipid
suspension to facilitate selective introduction of the chromophore
to sebaceous glands. Specifically, a chromophore may be placed in a
lipid suspension by mixing an oil, a chromophore, which has been
previously dissolved in a small amount (relative to the amount of
oil) of water or alcohol, and one or more surfactants. Following
vigorous stirring or shaking, the chromophore, dissolved in small
water droplets, is suspended as an emulsion in the lipid. Following
topical application, the suspended chromophore is then carried to
the sebaceous glands due to its close association with the
lipid.
[0041] The exact makeup of the lipid chromophore suspension may
vary, and can include at least one pharmaceutically acceptable oil,
at least one surfactant, and at least one chromophore dissolved in
water or alcohol. Pharmaceutically acceptable oils for use in
preparing lipid chromophore suspensions include, but are not
limited to olive oil, sesame oil, corn oil, and safflower oil.
Alternatively, the chromophore may be solubilized in one or more
liquid vitamins, such as a tocopherol (Vitamin E), to provide for
delivery of the chromophore and to promote epidermal health and
maintenance.
[0042] As a general guideline, the ratio of oil to dissolved
chromophore solution used to prepare a lipid chromophore suspension
should be at least about 5:1, about 10:1, about 20:1, about 50:1,
about 100:1, or even as high as 200:1 or more by volume. The
chromophore is preferably, but not necessarily, dissolved in water
or an alcohol acceptable for human topical administration at a
concentration close to the limit of solubility for that
chromophore. A preferred method of delivering ICG to the sebaceous
gland would be a lotion with liposome-encapsulated ICG. The
absorption and fluorescence characteristics of such lotion must be
known to properly design the in vitro and in vivo experiments. A
lipid suspension of ICG was prepared using the following protocol.
6 mg of ICG were dissolved in 20 g of water. 3 g of the solution
were mixed with 9 g Tween 80, 15 g Span 80 and 23 g olive oil. The
mixture was shaken for 1 min and left to settle for 3 days. The
resulting solution is a uniform transparent liquid with negligible
scattering. An identical clear lipid mix was prepared without
dissolving ICG in water.
[0043] In this way, the concentration of the chromophore is kept as
high as possible after mixing with surfactant and oil. Alcohols
acceptable for topical administration include, but are not limited
to ethanol, isopropanol and the like.
[0044] Surfactants useful in preparing lipid chromophore
suspensions include, but are not limited to Tween 80 and Span 80.
Generally, the surfactant comprises from 0.1% to 70% (w/v) of the
lipid chromophore suspension. The amount may be varied depending
primarily upon the amount and type of oil used and on the ratio of
oil to dissolved chromophore solution used. Generally, the amount
(mass or volume) of surfactant required varies in direct proportion
to the volume of dissolved chromophore solution used; the greater
the volume of chromophore dissolved in water or alcohol, the
greater the proportion of surfactant necessary to maintain the
lipid chromophore suspension.
[0045] The amount of chromophore added to a lipid chromophore
suspension can vary from about 0.01% to about 25% by weight of the
entire lipid chromophore suspension. The amount of chromophore used
is determined empirically, using, for example, varied proportions
of chromophore in lipid suspensions applied to the skin of an
animal, followed by microscopic inspection to evaluate the density
of chromophore localized in the sebaceous glands. Generally, the
better a chromophore suspension localizes to sebaceous glands, the
lower the relative proportion of chromophore necessary in the lipid
chromophore suspension.
[0046] A specific lipid chromophore suspension was prepared as
follows. 15 mg of ICG powder was dissolved in 1 g (1 ml) of water,
followed by the addition of 3 g of Tween 80, 5 g of Span 80, and
7.667 g of olive oil. The suspension was vigorously shaken in a
covered 50 ml tube for 5 minutes. The absorption coefficient for
the resulting lipid chromophore suspension was measured and was
typically between 350 cm.sup.-1 and 690 cm.sup.-1.
EXAMPLE III
Selective Introduction of a Chromophore to Sebaceous Glands
[0047] The manner in which a chromophore is selectively introduced
to sebaceous glands depends upon whether the chromophore is
lipophilic or non-lipophilic. A lipophilic chromophore is dissolved
in a pharmaceutically acceptable oil and applied directly to the
area of skin one wishes to treat. A lipophilic chromophore is
dissolved in oil at a final concentration from about 0.001% to
about 20% (w/v), with the proportion determined empirically using
an animal model (e.g., the hamster ear model described herein or
other appropriate model for human skin as known in the art).
[0048] A non-lipophilic chromophore is applied as
chromophore-bearing liposomes or as a lipid chromophore suspension
prepared as described herein. Following application of either a
lipophilic chromophore in oil, chromophore-bearing liposomes or a
lipid chromophore suspension, either by swabbing, for example with
a cotton swab, a cotton ball or a paint brush, or by spraying or
pouring the chromophore-oil mixture on the area to be treated, the
mixture may be manually rubbed into the affected area to enhance
the degree and/or rate of penetration of the mixture into the
sebaceous glands. Generally, the mixture is contacted with the skin
for about 2 minutes to about 24 hours prior to irradiation. The
time of contact of the mixture and the concentration of chromophore
applied is determined empirically using an animal model for a given
chromophore preparation. The mixture may be applied to an entire
area, for example, the face, or to a smaller portion of the area
(e.g., a small portion of the face or back) one ultimately wishes
to treat.
[0049] A chromophore is considered "selectively introduced" to
sebaceous glands according to the invention if greater than or
equal to about 90% of the chromophore remaining associated with the
skin after removal of excess chromophore preparation from the skin
surface is observed in sebaceous glands. The proportion of a
particular chromophore localized to sebaceous glands from a
particular chromophore preparation (e.g., chromophore in oil or
chromophore in liposomes or lipid suspension) is determined using
an appropriate animal model, such as the hamster ear model
described herein. Hamsters are known to have sebaceous glands in
their ears. These glands are typically on the order of 200 .mu.m in
diameter, making them somewhat larger than typical sebaceous glands
in humans. Nonetheless, the hamster ear is a convenient and
instructive model for human skin and sebaceous glands.
[0050] For example, the non-lipophilic chromophore indocyanine
green was introduced to sebaceous glands present in skin of the
hamster ear according to the following method. The lipid
chromophore suspension was topically applied to hamster ears and
allowed to travel into the pores and sebaceous glands for 24 hours.
After this time, the hamsters were euthanized and their ears were
examined for evidence of ICG in the sebaceous glands. FIG. 1 shows
a photomicrograph of skin from a hamster ear treated with ICG,
illuminated under white light, and FIG. 2 shows the same region
illuminated under 810 nm light and observed through an 840 nm
bandpass filter. ICG fluorescence (840 nm) is stimulated by
irradiation with 810 nm light. Both the white light and
fluorescence micrographs of the treated region show the chromophore
is primarily localized to the sebaceous glands. Experimentally, it
is estimated that approximately 5% of sebaceous gland lipid is ICG
lipid.
[0051] Another method for evaluation of the ICG uptake is based on
the use of Sebutape.RTM. adhesive patches commercially available
from CuDerm Corp. (Dallas, Tex.). The patch consists of a
microporous film acting as a passive collector of sebum. After the
application of the ICG microemulsion and cleaning of the skin, a
Sebutape.RTM. patch will be applied to the skin and analyzed for
fluorescence. The lipid ICG microemulsion, if present on the skin
surface, would penetrate into the patch and the patch would
fluoresce under illumination with 810 nm light. The skin will be
cleaned and a new patch will be applied until there is no
fluorescence from the patch, thus indicating that the skin surface
is clean from ICG. A fresh patch will be applied to the clean skin
surface and kept there for an hour. After an hour on the skin, that
patch will be examined for sebum collection and fluorescence. If
the patch were applied to a skin site without active sebaceous
glands there would be no sebum collected in the patch and thus no
fluorescence. If the patch collects sebum, but there is no
fluorescence, the ICG microemulsion did not penetrate in the sebum
contained in the sebaceous gland. Such result would indicate that
the application procedure for the ICG microemulsion has to be
improved, e.g. it has to be applied for a longer time. If the patch
collects sebum and there is fluorescence, the sebaceous glands are
successfully loaded with ICG and they can be treated with the
laser. The intensity of the fluorescence signal can be related to
the ICG concentration in the sebum and the treatment fluence can be
adjusted accordingly.
[0052] Another method for evaluation of the ICG uptake is with an
appropriate imaging system. This imaging system will incorporate a
monochrome CCD camera with a removable band-pass filter designed to
selectively detect the ICG fluorescence. It will also incorporate
various objectives to allow either large field, low resolution
imaging or narrow field, higher resolution imaging. The camera will
be connected to a frame grabber in a computer in order to digitally
record the images and perform image treatment. It would be possible
to identify the ICG loaded sebaceous glands and hair follicles on
the fluorescence image. In addition, it is possible that the
fluorescence image would reveal a residual layer of ICG
microemulsion on the skin surface. Such layer would have a
deteriorating effect on the penetration ability of the laser during
the treatment and would contribute to unnecessary heating of the
epidermis. The presence of such residual layer would indicate that
the skin cleaning procedure would have to be repeated. The
intensity of the fluorescence signal from the sebaceous glands can
be related to the ICG concentration in the sebum and the treatment
fluence can be adjusted accordingly.
[0053] Selective delivery of ICG in the sebaceous glands in human
skin using a biopsy sample was performed. For this study, an
eligible patient was scheduled to have some undesirable skin
lesions surgically excised. The day before the surgery, an
ICG-containing lipid solution was applied to the margin area of the
skin that is normally excised around the skin lesion. After the
surgical excision of the lesion and the margin area, the margin
area was sent for fluorescence analysis. The samples of excised
marginal skin were sectioned as thin slices and mounted on
microscope slides. FIG. 3 shows the images obtained from such
sample with normal light (left panels) and with a fluorescence
band-pass filter under illumination with the 810 nm diode laser
(right panels). The dashed arrow points to a pilosebaceous unit
with attached sebaceous gland.
[0054] The fluorescence photographs confirm the selective delivery
of the ICG microemulsion to the sebaceous glands in the human skin.
The absence of fluorescence at the skin surface means that the
excess ICG microemulsion was removed from the skin surface and thus
there is no risk of injuring the epidermis with heat generated in a
residual ICG film.
EXAMPLE IV
Methods of Clearing Obstructed Pores Prior to Chromophore
Administration
[0055] According to an additional embodiment of the present
invention, the surface of the skin to be treated with the
chromophore is cleaned prior to chromophore administration to
remove any excess surface oils and debris which could potentially
block the lipophilic absorption of the chromophore into the
targeted sebaceous glands. When subjected to the cleaning step,
pores which may be either partially or wholly obstructed by buildup
of sebum, oil, dirt, cosmetics or other foreign material are
partially or wholly cleared to allow or otherwise improve access of
the chromophore to the sebaceous gland. In this manner, delivery of
the chromophore to the targeted sebaceous gland is enhanced when
compared to administrations of chromophores where the skin has not
been cleaned and the pores have not been cleared.
[0056] According to this aspect of the present invention, a 10
cm.times.10 cm area of skin to be treated was wiped with an alcohol
swab. A 70% glycolic acid solution was then applied to the skin
surface and then left on for about 5 minutes. The glycolic acid
solution was then neutralized with GLYTONE.RTM. post peel
neutralizer available from Genesis Pharmaceutical Inc. (Morristown,
N.J.), and the area was dried. Other suitable neutralizing agents
include but are not limited to water, sodium bicarbonate solutions,
e.g. 5% sodium bicarbonate, etc. The neutralization process was
performed by wiping the area with water, e.g. using a water-soaked
gauze pad, and subsequently applying a liberal amount of the
neutralizer on the treated skin area. The treated area was then
rinsed liberally with water. A lipophilic formulation of
indocyanine green was then topically applied to the skin area and
covered with an occlusive dressing for 24 hours.
[0057] Additional methods for removing excess surface oils and
debris from skin and for clearing pores include topical
administration of salicylic acid preparations in the forms of
washes, gels or peels; topical retinoic acid therapy; and
mechanical processes including microdermabrasion. The area of the
skin to be cleaned may optionally be heated to promote pore opening
and to facilitate better cleaning of the skin area. It is to be
understood that additional methods for clearing pores which are
useful in the present invention will become apparent to those
skilled in the art based upon the present disclosure.
EXAMPLE V
Irradiation of Sebaceous Glands Containing Selectively Introduced
Chromophore
[0058] Irradiation of an area of skin being treated by a method of
the present invention is accomplished with a laser that emits light
energy at a wavelength strongly absorbed by the selected
chromophore, but largely transmitted by the outer layers (first 1-2
mm) of the skin. For example, a preferred chromophore, indocyanine
green (ICG; also known as cardio green) absorbs strongly at 810 nm,
a wavelength at which melanin, the primary human skin pigment, does
not absorb strongly. Thus, a laser emitting light at this
wavelength is preferred if ICG is used as the chromophore.
[0059] The laser radiant energy, or fluence of laser light useful
according to the invention will vary with the absorption
coefficient of the chromophore used and may be predicted by a Monte
Carlo simulation of the laser-tissue interaction, or may be
determined empirically using an appropriate animal model. In a
Monte-Carlo computer simulation, the occurrence of each of the
possible mechanisms for interaction between the laser radiation and
the target tissue is assigned a probability. The path of a single
quantum of laser radiation through the target tissue is then
divided into many small steps. At each step, the overall effect of
the radiation is determined by chance consistent with the assigned
probabilities. This process is repeated many times until a
statistically valid picture of the overall effect is obtained. In a
typical application, experimental data are used to determine the
probability assignments. There is a number of Monte-Carlo
simulation packages that are commercially available. The
Monte-Carlo simulation package used here is derived from the work
of L. H. Wang, S. L. Jacques, and L. Q. Zheng, "MCML--Monte Carlo
Modeling of Photon Transport in Multi-layered Tissues", Computer
Methods and Programs in Biomedicine 47, 131-146 (1995) and L. H.
Wang, S. L. Jacques, and L. Q. Zheng, "CONV--Convolution for
Response to a Finite Diameter Photon Beam Incident on Multi-layered
Tissues", Computer Methods and Programs in Biomedicine 54, 141-150
(1997) and is available through the Internet.
[0060] The fluence is directly related to laser intensity, and
should be maintained as low as possible to effect thermal
disruption of sebaceous glands that have concentrated the
chromophore while limiting damage to surrounding tissues. Optimal
fluences range from about 0.1 J/cm.sup.2 to about 50 J/cm.sup.2.
For indocyanine green, for example, it is preferred that the
fluence of the light emitted by the laser is in the range of about
5 J/cm.sup.2 to about 40 J/cm.sup.2.
[0061] It is preferred that the laser be pulsed during the
irradiation of the area being treated. Pulse duration may vary over
a range of approximately 1 .mu.sec to approximately 500 msec,
depending upon the laser used, the chromophore used, and the amount
of chromophore selectively introduced to the sebaceous glands.
Longer pulses are generally more effective for disruption of larger
glands that have longer thermal relaxation times than are short
pulses. When using indocyanine green as the chromophore, for
example, the pulse duration should be about 1 to about 100
msec.
[0062] The pulse duration and fluence determine the laser intensity
delivered to the treated area. The intensity should be low enough
to minimize the formation of a shockwave that can damage
surrounding tissue and to minimize tissue vaporization or explosive
tissue ablation.
[0063] According to the present invention, the amount of ICG that
must be introduced and the fluence required to damage the sebaceous
gland is estimated based upon the estimated temperature rise in the
gland at a given fluence and pulse duration. A temperature rise of
30.degree. C. sustained for more than about 10 msec is sufficient
to disrupt the gland. Tables I and II show the results of such
estimates obtained by means of a Monte Carlo simulation of the
laser:tissue interaction. For this estimate, the gland is assumed
to have 5% ICG lipid. The results depend strongly upon the
absorption coefficient of ICG in the lipid chromophore suspension.
Experimentally, this coefficient was found to lie between the
limits given in the tables (i.e., 350 cm.sup.-1 to 690
cm.sup.-1).
[0064] The expected temperature rise (.DELTA.T) of a gland for the
case in which fluence incident in the tissue is 10 J/cm.sup.2 and
the pulse duration is either 50 or 20 msec are shown in Tables I
and Table II respectively. TABLE-US-00001 TABLE I Calculated
Temperature Rise Expected within the Sebaceous Gland in .degree. C.
Pulse Duration 50 ms, 10 J/cm.sup.2 on the skin surface in a 5 mm
spot (39W) Gland Diameter Lipid ICG 50 .mu.m 100 .mu.m 200 .mu.m 5%
350 cm.sup.-1 3 10 30 5% 690 cm.sup.-1 6 19 55
[0065] TABLE-US-00002 TABLE II Calculated Temperature Rise Expected
in the Sebaceous Gland in .degree. C. Pulse Duration 20 ms, 10
J/cm.sup.2 on the skin surface in a 5 mm spot (98W) Gland Diameter
Lipid ICG 50 .mu.m 100 .mu.m 200 .mu.m 5% 350 cm.sup.-1 5 19 49 5%
690 cm.sup.-1 10 35 89
[0066] The size of the gland has an effect on the expected
temperature rise, as seen in the table, with a nearly 10-fold
increase in expected .DELTA.T in 200 .mu.m glands compared to 50
.mu.m glands at either fluence or pulse duration setting. It is
evident from the table that at 1% lipid solution uptake, and if the
absorption coefficient of the lipid chromophore solution is
actually closer to the lower limit given, that one would need to
increase the fluence above 10 J/cm.sup.2 to achieve disruption of
the gland. On the other hand, at the upper limits of both the
absorption coefficient and lipid chromophore uptake, 10 J/cm.sup.2
suffices to achieve disruption. With a lower pulse, 10 J/cm.sup.2
may be sufficient to achieve disruption in the larger glands.
[0067] Since one experimentally finds approximately 5% of the gland
volume is filled with lipid chromophore solution, the range of 5
J/cm.sup.2 to 40 J/cm.sup.2 for fluence and 1 msec to 100 msec for
fluence will allow the practitioner to achieve disruption of a
broad range of gland sizes.
[0068] Laser energy may be transmitted to the area being treated
by, for example, a commercially available optical fiber. One end of
the fiber is affixed to a laser light source, such as a diode laser
that emits light in a wavelength strongly absorbed by the selected
chromophore, and the other end is directed towards the area to be
irradiated. The size of the optical fiber aperture, e.g. the
diameter of the spot emitted by the optical fiber, is selected
based upon the size of the area to be treated, with smaller fibers
suited to smaller areas and larger fibers suited to larger areas.
The laser itself is connected to a control panel to enable the user
to turn the laser on and off and to adjust the fluence and pulse
rate of the laser energy.
[0069] The laser energy may be applied by scanning the emitting end
of the optical fiber over the area being treated. Scanning is
accomplished by manually moving the optical fiber or the laser
itself over the area being treated. Alternatively, it is
contemplated that the scanning may be accomplished mechanically by
mounting the laser or the emitting end of the optical fiber on a
scanning apparatus designed to move at a controlled rate. In this
manner the total laser energy applied to any one given area may be
kept constant. Clearly, this latter approach is most useful when
relatively large areas are to be treated.
[0070] While any laser that emits light energy at a wavelength and
intensity sufficient to disrupt the function of sebaceous glands
that have had a chromophore selectively introduced is acceptable
for use in the methods of the invention, a preferred embodiment
employs a diode laser and indocyanine green as the chromophore. It
is preferred that the diode laser have a wavelength range of 750 nm
to 1100 nm, a pulse duration ranging from about 1 to about 100
msec, and a fluence range of about 5 J/cm.sup.2 to about 40
J/cm.sup.2.
[0071] A human volunteer with active acne on the back had a small
area treated with the ICG microemulsion and the laser. Twenty-four
hours after the treatment a punch biopsy sample was taken from the
treated area and it was processed for histological examination.
FIGS. 4A and 4B show the results of a histological examination. The
low power view (FIG. 4A) and the high power view (FIG. 4B) both
show that the folliculosebaceous units have largely been destroyed
with surrounding tissue necrosis. Without wishing to be bound by an
scientific theory, a pathology analysis revealed that the
folliculosebaceous unit at the far left of FIG. 4A had largely been
destroyed with surrounding tissue necrosis. The pathology analysis
further revealed that the folliculosebaceous unit in the middle of
the field in FIG. 4A also was largely destroyed with acute
inflammation and necrosis involving the follicular epithelium.
Without wishing to be bound by any scientific theory, a pathology
analysis under high power (FIG. 4B) revealed that the left
folliculosebaceous unit had a destroyed follicle and the middle
folliculosebaceous unit had acute inflammatory cells present within
follicular epithelium in the middle.
EXAMPLE VI
[0072] The effectiveness of treatment in reducing sebum production
is determined by direct measurement of sebum production following
the laser irradiation. Sebum production is measured, for example,
using a specialized sebum-absorbent tape, SEBU-TAPES.TM. (CuDerm
Corp., Dallas, Tex.) and image analysis techniques. SEBU-TAPES.TM.
are white, open celled, microporous, hydrophobic films coated with
an adhesive layer that adheres to the skin surface. As sebum is
secreted, it is absorbed by the tape, displacing air in the
microcavities. As the microcavities in the tape fill with sebum,
the lipid-filled cavities become transparent. The area covered by
transparent spots per cm.sup.2 is a convenient and reproducible
measure of sebum production (Manuskiatti et al., 1999, J. Amer.
Acad. Dermatol. 41: 176-180). In order to observe a change in sebum
production following treatment with the methods of the invention,
one may either measure a treated area and an untreated nearby area
on the same individual, or one may measure sebum production over a
standard amount of time (e.g., 10 min to 10 hrs) on the area to be
treated both before and after treatment. Sebum production is
considered "reduced" according to the invention if it is at least
20%, preferably at least 40%, more preferably at least 50%, 60%,
70%, 80% or even greater than or equal to 90% lower relative to
sebum production either by untreated skin in a similar location or
by the treated area prior to treatment.
[0073] An alternative method of measuring sebum production is to
examine hematoxylin and eosin-stained sections of punch biopsy
tissue from treated and untreated areas of the same individual,
taking note of the size and morphology of the sebaceous glands
before and after treatment. Altered morphology of sebaceous glands
is generally indicative of successful treatment, since altered
gland morphology is associated with reduced sebum production.
[0074] The reduction of sebum production accomplished through the
inventive method results in a reduction in the presence and/or
severity of acne. The presence or severity of acne may be
quantified according to the method of Michaelsson et al. (1977,
Arch. Determatol. 113: 31-36). Briefly, the number of comedones,
papules, pustules and infiltrates in an area to be treated are
recorded. Each type of lesion is given a severity index: 0.5 for
comedones, 1 for papules, 2 for pustules and 3 for infiltrates. A
total score that corresponds to the severity of the disease is
obtained by multiplying the number of each type of lesion with its
severity index and calculating the sum of the various lesions
(Sigurdsson et al., 1996, Dermatology 194: 256-260). A decrease in
the acne severity score of at least 10% or more, preferably 25% or
more, 50% or more, 75% or more up to and including a decrease to
the score of zero (i.e., no acne), is indicative of reduced acne
severity or presence according to the invention.
EXAMPLE VII
[0075] 10 treatment sites were chosen on the backs of patients with
active acne. Topical indocyanine green dye in a lipophilic carrier
was then applied to a 10 cm.times.10 cm area treatment site and
covered with an occlusive dressing for 24 hours. The area was then
cleaned with alcohol and treated with laser irradiation with a
laser from Cynosure, Inc. (Chelmsford, Mass.). The following laser
parameters were used: wavelength of 800 nm, 4 mm spot size, 50 msec
pulse duration with a pulse fluence of 40 J/cm.sup.2. Photographs
of the treatment area were taken prior to the laser irradiation
(FIG. 5A) as well as 10 days (FIG. 5B), 10 weeks (FIG. 5C), and 10
months (FIG. 5D) post irradiation. The photographs taken 10 days,
10 weeks, and 10 months post treatment showed a significant
reduction in the presence of visible acne (see rectangular regions
in FIGS. 5B, 5C and 5D).
[0076] In addition to the treatment of existing acne, the invention
also provides a way to prevent the development of acne. The method
essentially comprises the steps of selectively introducing a
chromophore to sebaceous glands, and then irradiating the sebaceous
glands and surrounding area with laser light of a wavelength that
is essentially transmitted by the outer layers of human skin and is
strongly absorbed by the chromophore. The irradiation is performed
at a light fluence and for a time sufficient to disrupt sebaceous
gland function such that the development of acne is prevented.
[0077] It is to be understood that the embodiments of the present
invention which have been described are merely illustrative of some
of the applications of the principles of the invention. Numerous
modifications may be made by those skilled in the art based upon
the teachings presented herein without departing from the true
spirit and scope of the invention.
* * * * *