U.S. patent application number 12/606541 was filed with the patent office on 2011-03-24 for use of secondary optical emission as a novel biofilm targeting technology.
This patent application is currently assigned to NOMIR MEDICAL TECHNOLOGIES INC. Invention is credited to Eric Bornstein.
Application Number | 20110070552 12/606541 |
Document ID | / |
Family ID | 34435011 |
Filed Date | 2011-03-24 |
United States Patent
Application |
20110070552 |
Kind Code |
A1 |
Bornstein; Eric |
March 24, 2011 |
USE OF SECONDARY OPTICAL EMISSION AS A NOVEL BIOFILM TARGETING
TECHNOLOGY
Abstract
Provided herein are methods and compositions useful for the
treatment of periodontal disease exploiting optical and thermal
emissions of near-infrared laser systems and fibers in order to
target chromophore-stained biofilm while minimizing damage to
healthy tissues.
Inventors: |
Bornstein; Eric; (Natick,
MA) |
Assignee: |
NOMIR MEDICAL TECHNOLOGIES
INC
|
Family ID: |
34435011 |
Appl. No.: |
12/606541 |
Filed: |
October 27, 2009 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10961796 |
Oct 8, 2004 |
7621745 |
|
|
12606541 |
|
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60509685 |
Oct 8, 2003 |
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Current U.S.
Class: |
433/29 ;
433/217.1 |
Current CPC
Class: |
A61C 1/0046 20130101;
A61N 5/0601 20130101; A61N 5/062 20130101; A61N 2005/0606 20130101;
A61N 2005/0659 20130101; A61C 19/063 20130101; A61N 2005/067
20130101; A61P 1/02 20180101; A61N 5/0603 20130101 |
Class at
Publication: |
433/29 ;
433/217.1 |
International
Class: |
A61C 19/06 20060101
A61C019/06; A61N 5/067 20060101 A61N005/067 |
Claims
1. A kit for the treatment of periodontal disease in a periodontal
or periimplant tissue of a patient having periodontal disease
comprising: A. a optical fiber extending between a proximal end and
a distal end, the proximal end being adapted to receive optical
energy incident thereon in a near infrared spectral range, the
optical fiber being adapted to transmit the received optical energy
to the distal end, and the distal end being adapted to respond to
the transmitted optical energy incident thereon, to emit, upon
contact with at least a portion of the tissue, optical energy in a
predetermined spectral range, wherein the predetermined spectral
range differs from the near infrared spectral range; B. a reservoir
adapted to store a chromophore dye, the dye characterized by an
absorption spectrum in the predetermined spectral range, the
reservoir including an applicator assembly adapted to effect
selective application of the chromophore dye to a region of the
tissue.
2. A kit according to claim 1, wherein the predetermined spectral
range is from about 600 nm to about 700 nm.
3. A kit according to claim 2, wherein the optical energy is at a
wavelength of about 830 nm.
4. A kit according to claim 1, further comprising an optical energy
source for generating optical energy in the near infrared spectrum,
and an associated coupling assembly for coupling the optical energy
to the proximal end of the optical fiber.
5. The kit according to claim 4, wherein the predetermined spectral
range is from about 600 nm to about 700 nm.
6. The kit according to claim 5, wherein the generated optical
energy is coherent.
7. The kit according to claim 6, wherein the optical energy source
is a diode laser operating at about 500-1200 mW, for generating the
optical energy at a wavelength of about 830 nm.
8. The kit according to claim 1, wherein the chromophore dye is
selected from the group consisting of Methylene Blue, Toludine
Blue, Congo Red, and Malachite Green, the dye being disposed in the
reservoir.
9. The kit according to claim 1, wherein the distal end of the
optical fiber is fused silica.
10. The kit according to claim 1, wherein lateral surfaces of the
optical fiber extending from the distal end toward the proximal
end, are adapted to cause optical radiation incident thereon and
propagating in the optical fiber from the distal end, to be
refracted and pass through the lateral surfaces.
11. A method for the treatment of periodontal disease in a
periodontal or periimplant tissue of a patient having periodontal
disease comprising the steps of: applying a chromophore dye
composition to the tissue, the dye composition comprising at least
one dye that absorbs light energy comprising at least one
wavelength in a range of about 600 nm to 700 nm; and irradiating
the periodontal or periimplant tissue with laser energy comprising
at least one wavelength in a range from about 800 nm to about 1064
nm emanating from an optical fiber.
12. The method according to claim 11, wherein the energy is
coherent.
13. The method according to claim 11, wherein the laser energy is
in the near infrared spectrum and is coherent.
14. The method according to claim 11, wherein the laser energy is
generated by a diode laser operating at 500-1200 mW.
15. The method according to claim 11, wherein the laser energy
comprises a wavelength of 830 nm.
16. The method according to claim 11, wherein the dye composition
is selected from the group consisting of Methylene Blue, Toludine
Blue, Congo Red, and Malachite Green.
17. The method according to claim 11, wherein the optical fiber is
contacted with at least a portion of the tissue.
18. The method according to claim 11, wherein the step of
irradiating the periodontal or periimplant tissue is for a
therapeutically effective time in a moving pattern.
19. The method according to claim 11, wherein a solid coagulum is
formed in proximity of the periodontal or periimplant tissue upon
irradiating the tissue with laser energy.
20. The method according to claim 18, further including the step of
mechanically removing the solid coagulum from the tissue by
conventional periodontal scalers or ultrasonic scalers.
21. The method according to claim 17, further including the step of
administering a therapeutically effective amount of an antibiotic
to the patient having periodontal disease.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Ser. No. 60/509,685
filed on Oct. 8, 2004.
BACKGROUND
[0002] 1. Field of the Invention
[0003] The present invention relates to live biofilm targeting and
subsequent bacterial thermolysis for its eradication in the human
body, utilizing secondary quantum optical and thermal emissions
from the distal end of near infrared laser delivery fibers.
[0004] 2. Relevant Technologies
[0005] To date, in excess of 300 different species of bacteria have
been described in the human oral cavity (Moore W. E., The Bacteria
of Periodontal Diseases, Periodontol. 2000). Most bacteria are
found in dental plaque and in the sub-gingival periodontal and
periimplant pockets. These sub-gingival bacteria have evolved to
fight and inhibit the normal host defense system creating a unique
ecological niche in the periodontal pocket.
[0006] Subgingival bacteria find their nutrient base in the
crevicular fluid of the periodontal pocket. Even though these
bacteria are in direct proximity to the highly vascularized
periodontal and periimplant epithelium, they continue to grow and
thrive. Despite (and arguably because of) the host's immune and
inflammatory responses seeking to inhibit bacterial colonization
and intrusion into the tissues (e.g., mediated by lysozymes,
complement formation, bradykinin, thrombin, fibrinogen, antibodies
and lymphocytes), subgingival bacteria tend to prevail in the
periodontal and/or periimplant pocket providing a unique
environmental niche (Cimasoni, Monogr. Oral Sci. 12:III-VII, 1-152
(1983)).
[0007] To successfully treat the periodontal and/or periimplant
pocket and periodontal/periimplant disease as a whole, the local
inflammation and its cause must be eliminated, in an effort to
re-establish an intact barrier against the root of the tooth. A
newly regenerated periodontal ligament or epithelial barrier
connected to the root of the tooth or implant will limit the space
available for bacterial growth. Once the cause of the immune and
inflammatory responses is eliminated, the periodontal tissues will
likely heal. When dealing with implants, the disease is even more
recalcitrant and difficult to eliminate, because of the unique and
foreign three dimensional architecture and roughened surface of
most commercial dental implants.
[0008] Healing can be seen as new collagenous and epithelial
attachments begin to form in the area just inferior to the base of
the periodontal pocket. These new periodontal ligament fibers
generally occur only in areas not previously exposed to live
bacteria in the pocket. In contrast, the epithelial seal known as
long junctional epithelium (i.e., a strong epithelial adaptation to
the root surface) generally will occur in areas that were exposed
to the live biofilm of the periodontal pocket. With implants (where
a periodontal ligament does not exist) new bone formation and/or
long junctional epithelium are sought to reduce the available space
for bacterial growth.
Traditional Approaches
[0009] Periodontal/periimplant instruments have been invented and
designed over the years for the specific goal of plaque and
calculus removal, root planing and debridement, and removal of
diseased periodontal/periimplant tissues. In particular,
periodontal scaling, root planing and curettage instruments are the
mechanical approaches of choice to remove dental plaque, calculus,
diseased cementum, and diseased pocket soft tissues.
[0010] A number of pharmacological approaches have been developed
as an adjunct to traditional mechanical approaches to attack
bacteria (e.g., extended release antimicrobial formulations for
delivery in the periodontal/periimplant pocket after mechanical
debridement). However, these pharmacological modalities have
significant limitations because to be effective they must (a) reach
the intended site of action (a deep three-dimensional pocket), (b)
remain at an adequate concentration, and (c) last for a sufficient
duration of time.
[0011] To remain at an adequate concentration and last for a
sufficient duration of time, the intrasulcular delivery vectors of
the antimicrobials (e.g., resorbable gels, resorbable microspheres,
and antimicrobial impregnated chips) must fill the physical space
of the periodontal pocket. Most of these vectors stay in place in
the periodontal pocket for the duration of the drug delivery
therapy (up to three weeks), and hence prevent the immediate
healing process of new periodontal attachment and long junctional
epithelium formation at the tooth/implant pocket interface after
mechanical debridement. In addition, the majority of local
antimicrobials used are bacteriostatic, and never fully eliminate
periodontal and/or periimplant pathogens from the treatment site.
Long term resistant strains often arise in the periodontal pocket
in response to sub-lethal antimicrobial absorption. Not
surprisingly, these local pharmacological modalities have been
reported to have only marginal success rates (The Role of
Controlled Drug Delivery for Periodontitis, Position Paper from
AAP, 2000) and to have severe limitations ultimately leading to
re-infection and continued disease progression.
Recent Developments: the Biofilm Paradigm
[0012] The recognition that subgingival dental plaque exists as a
living biofilm has shed some light on the underlying mechanism at
work (Periodontology 2000 (supra); and Chen, J. Calif. Dent. Assoc.
(2001).
[0013] Costerton et al., J. of Bacteriol. (1994), have described
biofilms as matrix enclosed bacterial populations adherent to each
other and/or to surfaces or interfaces. The same researchers have
also described biofilms as ecological communities that have evolved
to permit survival of bacterial the community as a whole, with
specialized nutrient channels within in the biofilm matrix (a
primitive circulatory system) to facilitate the movement of
metabolic wastes within the colony. If dental plaque and sub
gingival bacterial colonies are now viewed as a living biofilm,
there is a need (not only limited to dentistry) for effective
biofilm targeting techniques.
[0014] Current understanding of biofilms has conferred upon them
some basic properties (Marsh et al., Adv. Dent. Res. (1997)). These
include but are not limited to actual community cooperation between
different types of microorganisms, distinct and separate
microcolonies within the biofilm matrix, a protective matrix
surrounding the bacterial colonies, different distinct
microenvironments within different microcolonies, primitive
communication systems, and unique protection from and resistance to
antibiotics, antimicrobials, and the immunological and inflammatory
host response.
[0015] Most previous attempts to control periodontal diseases have
been performed based on traditional understanding of periodontal
and periimplant bacteria in in vitro. As a living biofilm (in vivo)
however, subgingival plaque and periodontal bacteria act and
function quite differently than the classical laboratory models
would predict. Periodontal and periimplant bacteria in a live
biofilm produce different and more harmful chemicals and enzymes
than they do in culture in the laboratory. Also, within a biofilm,
there is an increase in the spread of antibiotic resistance through
inter-species relationships.
[0016] The biofilm (a proteinaceous slimy matrix) itself serves as
an effective barrier of protection from many classical therapeutic
regimens targeting bacteria. Antibiotics may fail to even penetrate
the biofilm and reach the causative bacteria if they are
neutralized by resistant enzymatic reactions within the
biofilm.
[0017] This new understanding of the ethiology underlying
periodontal disease has thus identified a void and a need for novel
procedures targeting the biofilm directly to combat periodontal
disease and the recalcitrant biofilms that harbor and protect the
pathogenic bacteria. Such techniques are hereinafter referred to as
Biofilm Targeting Technologies (BTT).
[0018] Various dyes and other compounds have been proposed for the
express purpose of disinfecting or sterilizing tissues in the oral
cavity. It has been proposed to selectively target bacteria for
laser irradiation with chromophores in the oral environment to
expedite bacterial thermolysis. Specifically, there are proposals
for treating inflammatory periodontal and periimplant diseases
along with other lesions in the oral cavity, by: (a) contacting the
tissues, wound or lesion, with a redox agent (dye) such that the
bacteria themselves take up the compound, and are inhibited over
time, by the exogenous agent in the absence of a laser; or by (b)
contacting the tissues, wound or lesion, with a photosensitizing
compound (dye) such that the bacteria and/or tissues themselves
take up the compound, and then irradiating the tissues or lesion
with laser light (generally soft visible red lasers) at the
specific wavelength absorbed by the photosensitizing and targeting
chromophore.
[0019] Despite the large literature relating to the use of dyes and
laser irradiation in the context of treatment of oral cavity
tissues, there remains a need for effective direct targeting and
thermolysis in vivo of the biofilm which would minimize harm to
healthy tissues and promote healing.
[0020] In view of the foregoing, it would be an advancement in the
art to provide new approaches for use in treating periodontal and
periimplant disease that addressed the drawbacks of the approaches
presently available. In particular, it would be an advancement to
provide approaches for the treatment of bacterial fueled
inflammatory diseases by effectively targeting and destroying the
whole live biofilm (and consequently the bacteria) in the three
dimensional periodontal/periimplant space, without harming the
healthy dental or other tissues. In particular it would be an
advancement to provide novel methods for treating a diseased tissue
exploiting optical and thermal emissions of near-infrared diode
laser systems and fibers in order to target chromophore stained
biofilm while minimizing damage to healthy tissues. Furthermore, it
would be a desirable advancement to identify methods and means for
targeting disease tissue with increased specificity as evidenced by
a better control of the coagulation zone of incision with reduced
deeper effects.
SUMMARY OF THE INVENTION
[0021] The present invention provides a novel approach and
compositions (including kits) to expand the therapeutic window of
opportunity currently available with conventional dental solid
state diode and Nd:YAG lasers in the near infrared spectrum to
coagulate live biofilm and kill bacteria thermally without harming
the healthy dental structures and tissues of the patient.
[0022] To accomplish biofilm coagulation and bacterial thermolysis
with a laser (e.g., a dental diode or Nd:YAG laser), there is a
small therapeutic window of opportunity available to eliminate the
live biofilm and oral pathogenic bacteria from periodontal and
periimplant sites. This is accomplished as the optical energy from
the laser is converted to local thermal energy in the target site
and tissue. Because this therapeutic window is so small, a method
is presented to expand the range of the dental diode and Nd:YAG
laser to make live biofilm coagulation and bacterial elimination
through the thermal deposition of energy a safer and more
predictable process. The present invention uses localized delivery
of targeting chromophore for the live biofilm in the periodontal or
periimplant site. This allows the two parameters, of (1) energy
output of the laser and (2) time of laser application, to be
lowered to accomplish the tasks of live biofilm coagulation and
subsequent bacterial thermolysis in a safer environment.
BRIEF DESCRIPTION OF DRAWINGS
[0023] For a fuller understanding of the nature and objects of the
present invention, reference is made to the following
specification, which is to be taken in connection with the
accompanying drawings wherein:
[0024] FIG. 1 is a graph illustrating the spectral radiant exitance
of a blackbody radiator at different temperatures. On the ordinate
(y axis) are shown various optical densities and on the abscissa (x
axis) are shown various wavelengths.
[0025] FIG. 2 is a diagram illustrating a chromaticity map for a
representative chromophore dye according to the invention:
Methylene Blue.
[0026] FIG. 3A is a diagram illustrating a clean cleaved optical
fiber tip before blackbody reaction according to the invention.
[0027] FIG. 3B is a diagram illustrating the secondary optical and
thermal energy generated from a carbonized laser delivery fiber
according to the invention.
[0028] FIG. 4. is a diagram illustrating the optical fiber now
converted to an incandescent blackbody radiator (the "hot tip" of
the invention) in contact with the tissue being treated (i.e., the
periodontal pocket).
[0029] FIG. 5 is a diagram illustrating a syringe as an example of
a delivery system for the delivery of Methylene Blue to the
periodontal or periimplant pocket by use of a syringe.
[0030] FIG. 6 is a photograph showing the optical fiber now
converted to the "hot tip" of the invention identifiable as an
incandescence.
[0031] FIG. 7 is a diagram illustrating an especially adapted
optical fiber tip according to one of the embodiments of the
invention, showing the etched fiber wall and the distal end of the
optical fiber.
DETAILED DESCRIPTION
[0032] The present invention capitalizes on the discovery that
significant and factual quantum interactions occur with the distal
end of near-infrared laser delivery optical fibers, when the tip of
the optical fiber of a near-infrared diode or Nd:YAG laser comes
into contact with periodontal/periimplant tissues and instantly
becomes a carbonized "hot tip". These quantum and thermodynamic
realities are exploited to achieve targeted live biofilm
thermolysis using near-infrared lasers and the secondary quantum
emissions from the optical fiber (delivery tips) used according to
the invention.
[0033] The inventor has devised inter alia novel contact "hot tip"
techniques exploiting the instantaneous transformation of the laser
optical fibers (e.g., the silica fibers) in the delivery device of
conventional near-infrared diode or Nd:YAG lasers into incandescent
blackbody radiators capable of cutting and vaporizing tissues (see
FIG. 1 showing the spectral radiance of a blackbody radiator at
different temperatures). Such incandescent blackbody radiators have
been found to have quantum and thermodynamic properties useful for
the treatment of diseased periodontal and/or periimplant tissues
and specifically for the reduction of live biofilm.
[0034] When an unclad optical fiber tip emitting photons (FIG. 3A)
to a target tissue comes in contact with a live biofilm, or other
biological matter such as blood, it will immediately accumulate
debris that "stick" to the fiber itself. This debris has been found
to immediately absorb the intense near-infrared laser energy
propagating through the optical fiber thereby causing an increase
in temperature and carbonization of the same (hence the term "hot
tip" henceforth designating the blackbody incandescent tip and the
carbonized coagulum). The temperature escalates as the energy from
the infrared laser photons continues to bombard (and be absorbed
by) the newly carbonized hot tip. Upon its conversion to a
blackbody radiator (and as it becomes incandescent and it glows,
see FIG. 3B), the optical fiber generates a secondary visible
optical emission (see FIG. 6).
[0035] As used in this specification, the singular forms "a," "an"
and "the" specifically also encompass the plural forms of the terms
to which they refer, unless the content clearly dictates otherwise.
As used in this specification, whether in a transitional phrase or
in the body of the claim, the terms "comprise(s)" and "comprising"
are to be interpreted as having an open-ended meaning. That is, the
terms are to be interpreted synonymously with the phrases "having
at least" or "including at least". When used in the context of a
method, the term "comprising" means that the process includes at
least the recited steps, but may include additional steps. When
used in the context of a composition, formulation or a kit the term
"comprising" means that the compound or composition includes at
least the recited features or components, but may also include
additional features or components.
[0036] The methods and compositions according to the invention thus
combine the primary emissions of conventional near-infrared diode
or Nd:YAG lasers with the secondary quantum emissions from the
optical laser used according to the invention for the treatment of
chromophore-stained periodontal or periimplat tissue to target live
biofilm thus treating periodontal disease in a tissue (e.g., in the
oral cavity). One of skill will appreciate that while the invention
is exemplified in the dental field, it may be applied in many other
fields targeting infections in virtually any tissue. Hence, for
example the tissue could be the hip, where irrigation with a
chromophore (e.g., 1% Methylene Blue solution) and the subsequent
use of a laser according to the invention will coagulate the
targeted infection in that area of the body. Furthermore, while the
invention is exemplified in human patients, the methods and
compositions of the present invention are intended for use with any
mammal that may experience the benefits of the method and
composition of the invention. Foremost among such mammals are
humans, although the invention is not intended to be so limited,
and is also applicable to veterinary uses. Thus, in accordance with
the invention, "mammals," or "mammal in need," or "patient" include
humans as well as non-human mammals, particularly domesticated
animals including, without limitation, cats, dogs, and horses.
[0037] A large number of laser sources in the infrared spectrum
have been used to kill pathogenic bacteria in dentistry and
medicine. For the last few years near infrared solid state diode
and Nd:YAG lasers have been used in the field of dentistry for
tissue cutting, cautery, and bacterial thermolysis. The four most
widely used dental near infrared wavelengths are 810 nm, 830 nm,
980 nm and 1064 nm. These near infrared lasers have very low
absorption curve in water, and have a very deep tissue penetration
values as detailed infra.
[0038] The patents, published applications, and scientific
literature referred to herein establish the knowledge of those with
skill in the art and are hereby incorporated by reference in their
entirety to the same extent as if each was specifically and
individually indicated to be incorporated by reference. Any
conflict between any reference cited herein and the specific
teachings of this specification shall be resolved in favor of the
latter. Likewise, any conflict between an art-understood definition
of a word or phrase and a definition of the word or phrase as
specifically taught in this specification shall be resolved in
favor of the latter.
[0039] Technical and scientific terms used herein have the meaning
commonly understood by one of skill in the art to which the present
invention pertains, unless otherwise defined. Reference is made
herein to various methodologies and materials known to those of
skill in the art.
[0040] An aspect of the invention provides novel methods for the
treatment of periodontal disease in a periodontal or periimplant
tissue of a patient having periodontal disease. The tissue being
treated by the methods of the invention is contracted with a heat
sink moiety including at least a dye absorbing at a predetermined
spectral range. A "heat sink" moiety is any entity capable of
receiving, absorbing, or otherwise diverting heat from the tissue
being irradiated. Heat sink moieties according to the invention
include compounds known to act as chromophore dyes (i.e., molecules
that preferentially absorb optical energy). The term "predetermined
spectral range" is from about 400 nm to about 1100 nm. In certain
embodiments, the chromophore dye has absorption bands (and thus a
predetermined spectral range of) from about 600 to about 700 nm. A
heat sink moiety needs to be essentially non-toxic to tissues,
needs to be able to penetrate live biofilm, and--most
important--needs to be selectively absorbed by the live biofilm to
target the same without damaging the patient tissues.
Representative non-limiting examples of chromophore dyes include
Toludine Blue (with absorption spectra between 600 to 700 nm),
Methylene Blue (MB, with absorption peaks at 609 (orange) and 668
nm (red)), Congo Red (with strong absorption band at 340 nm in the
near-ultraviolet region and another at 500 nm near the blue-green
transition region), and Malachite Green (with a strong absorption
band centered at 600 nm near the yellow-red transition region, and
any other tissue safe biological dye). One of skill will appreciate
that chromophore dyes may be administered in a composition form
including any known pharmacologically acceptable vehicle with any
of the well known pharmaceutically acceptable carriers, including
diluents and excipients (see Remington's Pharmaceutical Sciences,
18.sup.th Ed., Gennaro, Mack Publishing Co., Easton, Pa. 1990 and
Remington: The Science and Practice of Pharmacy, Lippincott,
Williams & Wilkins, 1995).
[0041] The term "about" is used herein to mean approximately, in
the region of, roughly, or around. When the term "about" is used in
conjunction with a numerical range, it modifies that range by
extending the boundaries above and below the numerical values set
forth. In general, the term "about" is used herein to modify a
numerical value above and below the stated value by a variance of
20%.
[0042] According to the methods of the invention, the
periodontal/periimplant tissue stained with the chromophore dye
(composition) is irradiated with optical energy in the near
infrared spectral range.
[0043] The skilled practitioner will realize that the instant
invention combining live biofilm chromophore targeting and
thermolysis, may be used to augment traditional approaches by
promoting healing upon removal of the live biofilm. Accordingly,
the methods and compositions of the invention could be used to
target the live biofilm in the periodontal or periimplant pocket
(see FIG. 4) followed by mechanical debridement of the denatured
biofilm (now reduced to a denatured and inactive solid coagulum
entrapping live and dead bacteria within their matrix in the
periodontal or periimplant pocket) and its constituent flora. By
this approach, the periodontal/periimplant instruments (e.g.,
periodontal scalers or ultrasonic scalers) are able to scale and
debride the denatured biofilm out of the local area with much
greater success than would be possible if the slimy live biofilm
remained uncoagulated. Live biofilm chromophore targeting thus,
achieves the goals of traditional bacterial removal by traditional
scaling and mechanical debridement. Moreover, it seeks out and
target previously inaccessible areas for periodontal/periimplant
pocket treatment and concurrently kills and removes the living
biofilm as a denatured inactive solid coagulum.
[0044] Similarly, the instant methods and compositions may be
combined with traditional approaches involving antibacterial
modalities found in the literature such as for example antibiotic
treatment (for a standard reference works setting forth the general
principles of pharmacology see, Goodman and Gilman's The
Pharmacological Basis of Therapeutics, 10.sup.th Ed., McGraw Hill
Companies Inc., New York (2001); for a general reference relating
to the use of antibiotics in dentistry see for example, Rose et
al., Periodontics: Medicine, Surgery, and Implants, June 2004 in
concomitance with or following laser treatment. Hence, as
exemplified hereinafter (see Example 2) a patient may be treated
with a penicillin to prevent reinfection. Such combinations may be
effected prior to, in conjunction with, and/or following laser
treatment (irradiation). Hence, formulations of compositions
according to the invention may contain more than one type of
chromophore dye according to the invention, as well any other
pharmacologically active ingredient useful for the treatment of the
symptom/condition being treated. Hence, in some instances the
practitioner may opt to co-administer other active or inactive
components including, but not limited to, antibiotics, analgesics,
and anesthetics. Examples of useful antibiotic or antimicrobial
agents include, but are not limited to, chlorhexidine gluconate,
triclosan, cetyl pyridinium chloride, cetyl pyridinium bromide,
benzalkonium chloride, tetracycline, methyl benzoate, and propyl
benzoate. Examples of useful anesthetic agents include, but are not
limited to, benzocaine, lidocaine, tetracaine, butacaine,
dyclonine, pramoxine, dibucaine, cocaine, and hydrochlorides of the
foregoing.
[0045] As used herein, by "treating" is meant reducing, preventing,
and/or reversing the symptoms in the patient being treated
according to the invention, as compared to the symptoms of an
individual not being treated according to the invention. A
practitioner will appreciate that the compounds, compositions, and
methods described herein are to be used in concomitance with
continuous clinical evaluations by a skilled practitioner
(physician or veterinarian) to determine subsequent therapy. Hence,
following treatment the practitioners will evaluate any improvement
in the treatment of the disease according to standard
methodologies. Such evaluation will aid and inform in evaluating
whether to increase, reduce or continue a particular treatment
dose, mode of administration, etc.
[0046] Live biofilm targeting and secondary emission coagulation of
the biofilm can be accomplished without harming collateral tissues,
healthy periodontal/periimplant architecture or the tooth. Further,
this can be accomplished without (necessarily) introducing
antibiotics or resorbable delivery vectors into the system or
periodontal pocket, and will allow for the immediate healing and
reattachment of periodontal tissues to begin.
[0047] The bacteria targeted in accordance with the present
invention are those specifically involved in art-known periodontal
and periimplant infections (e.g., Actinobacillis
actinomycetemcomitans, Porphyromonas gingivalis, Prevotella
intermedia/nigrescens, Bacteroides forsythus, Fusobacterium
species, Peptostreptococcus micros, Eubacterium species,
Camplobacter rectus, streptococci, and Candida species). Also
contemplated are art-known periimplant infectious bacteria (e.g.,
Fusobacterium spp., Prevotella intermedia, Porphyromonas
gingivalis, Actinobacillus actinomycetemcomitans, Peptostreptoccus
micros, Bacteroides spp., Capnocytophaga spp., Prevotella spp.,
Spriochetes, Staphylococcus spp., Enteric gram-negative bacteria,
Campylobacter gracilis, Streptoccus intermedius, Streptococcuc
constellatus, Candida albicans, and Eikenella corrodens).
[0048] The energy may be provided by any suitable source of
coherent energy, e.g., a laser, capable of emitting optical energy
having a wavelength from about 500 to about 1500 nm, if necessary
or convenient using optical fibers or other known optical devices
to deliver the energy to the periodontal and/or the periimplant
being treated. In certain embodiments, the optical energy generated
is coherent energy (e.g., generated by a laser such as a diode
laser or a Nd:YAG laser operating at 350-1200 mW, preferably at
500-1200 mW, or at 800-1200 mW). Thus, lasers according to the
invention include those emitting optical energy having a wavelength
of from about 500 to about 1500 nm, preferably from about 600 to
1100 nm, or from about 800 to about 1100 nm. In representative
non-limiting examples shown herein the wavelength is from about 800
to about 1064 nm.
[0049] There are generally five factors to consider regarding heat
generation by the primary emissions of near infrared lasers when
the distal end of the laser fiber is clean and well cleaved (as a
general reference, see Niemz M, Laser-Tissue Interactions.
Fundamentals and Applications, Berlin, Springer, pp 45-80, 2002)).
These factors are: (1) wavelength and optical penetration depth of
the laser; (2) absorption characteristics of exposed tissue; (3)
temporal mode (pulsed or continuous); (4) exposure time; and (5)
power density of the laser beam.
[0050] Diode lasers in the near infrared range have a very low
absorption coefficient in water, hence they achieve deep optical
penetration in tissues that contain 80% water (including the oral
mucosa, bone and gingiva). This means that for a conventional
dental diode soft tissue laser the depth of penetration per pulse
is estimated by Niemz to be about 4 cm. The shorter wavelengths of
the near-infrared diode and Nd:YAG lasers have very high absorption
peaks in molecules (chromophores) such as melanin and hemoglobin.
This will allow the laser energy to pass with minimal absorption
through water, producing thermal effects much deeper in the tissue
(as photons are absorbed by the deeper tissue pigments). This
photobiology allows for controlled deeper soft-tissue coagulation,
as the photons that emerge (in a cone pattern of energy) from the
distal end of a clean cleaved near-infrared diode laser fiber, are
absorbed by blood and other tissue pigments.
[0051] The next parameter to bear in mind is the heat effect on the
tissue being irradiated, based on the pulse mode of currently
available near-infrared systems. Presently, for periodontal
treatment, near-infrared lasers either emit photons in the
Continuous Wave (CW) or Gated CW Pulsed Mode for Diode systems, and
Free Running Pulsed (FRP) for Nd:YAG's. Thus, because the length
(duration) of the tissue exposure to the photon energy of the laser
will govern the thermal tissue interaction that is achieved.
[0052] In the CW or Gated CW mode, laser photons are emitted at one
single power level, in a continuous stream. When the stream is
Gated, there is an intermittent shuttering of the beam, as a
mechanical gate is positioned in the path of the beam, essentially
turning the laser energy on and off. The duration of on and off
times, of this type of laser system is generally on the order of
milliseconds (1 millisecond= 1/1000th of a second), and the
"power-per-pulse" stays at the average power of the CW beam. Nd:YAG
lasers (in the FRP mode) can produce very large peak energies of
laser energy, for extremely short time intervals on the order of
microseconds (1 microsecond= 1/1,000,000th sec). As an example, one
of these lasers with a temporal pulse duration of 100 microseconds,
with pulses delivered at ten per second (10 Hz), would mean that
the laser photons are hitting the tissue for only 1/1000th of a
second (total time) and the laser is "off" for the remainder of
that second. This will give the tissue significant time to cool
before the next pulse of laser energy is emitted. These longer
intervals between pulses will benefit the thermal relaxation time
of the tissue. The CW mode of operation will always generate more
heat than a pulsed energy application.
[0053] If the temporal pulses are too long (or the exposure in CW
is too long), the thermal relaxation effect in the tissues is
overcome and irreversible damage to non-target areas can occur. An
added safety feature is provided by the Methylene Blue acting as a
"heat sink" around vital tissues providing a larger margin of error
cooling and appropriate exposure times are miscalculated. So, not
only the ultimate temperature reached in the tissue interaction
with the laser energy is of concern, but also the temporal duration
of this temperature increase plays a significant role for the
induction of desired tissued effects, and the inhibition of
irreversable tissue damage. For nano- and pico-second pulses, heat
diffusion during the laser pulse would be negligible, however
presently available dental lasers cannot achieve such pulses.
[0054] The power density of the beam is determined by the peak
power generated by the laser, divided by the area of the focused
beam. This means that the smaller the diameter of the fiber used to
deliver the energy (200 .mu.m, 400 .mu.m, 600 .mu.m), and the
closer the fiber is to the tissue (i.e., a smaller "spot size", not
touching the tissue), the greater the power density (amount of
emitted photons per square mm of the beam) and the greater the
thermal interaction. With a non-contact "clean" fiber tip, the two
most important considerations are the spot size of the beam, and
the distance of the fiber tip to the tissue.
[0055] There is an immediate and profound change in the quantum
emissions of the laser fiber, and an immediate and profound change
in the tissue response and photobiology when an unclad "naked"
fiber tip comes in contact with periodontal and/or periimplant
tissue at any fluence above about 300 mW continuous output. This
occurs in 100% of all intrasulcular periodontal procedures using
simple naked unclad fibers, regardless of the diode laser or Nd:YAG
wavelength from approximately 600 nm to 1100 nm. When an unclad
"naked" fiber tip comes in contact with periodontal tissue and
intrasulcular fluids, cellular debris and biofilm will immediately
accumulate on the unclad tip, and this debris will instantly absorb
the intense infrared laser energy propagating through the fiber,
which will cause the tip to heat and immediately carbonize. As the
energy from the infrared laser photons continues to be absorbed by
this newly carbonized tip, (within as short a time as a single
second) the tip will become red hot (above 726.degree. C.). This
resulting secondary quantum emission of the "hot tip" energy to the
tissue is associated with different heat transfer and photobiologic
events in the periodontal pocket and periodontal tissues. That is
the primary focus of this invention. This allows the two
parameters, of (1) energy output of the laser and (2) time of laser
application, to be lowered to accomplish the tasks of live biofilm
coagulation and subsequent bacterial thermolysis in a safer
environment.
[0056] By direct live biofilm chromophore targeting, and for the
first time exploiting the inherent secondary quantum emissions with
this hot tip technique and the chromophore Methylene Blue, the
operator of an 800 nm-1064 nm dental laser can decrease the power
of the laser to approximately 0.05-1.5 Watts, and decrease the time
needed in the area of treatment. Even with turning down the
energies, and treating the area of the periodontal or periimplant
pocket for less time than would be necessary without the
chromophore heat sink, live biofilm phase change through
coagulation and thermolysis of the bacteria within the biofilm will
occur. This will lead to a safer procedure for the patient, and
preserve more collagen, bone, and mucosa in the
periodontal/periimplant pocket from irreversible thermal damage
during the procedure.
[0057] With the "hot tip" technique the deeply penetrating primary
laser energy is substantially reduced, and the photobiology and
laser-tissue interaction is different from what is found when using
a non-carbonized fiber that emits only the primary emission,
near-infrared photons. To accomplish safe and predictable
periodontal/periimplant procedures with a "hot tip", the clinician
must be mindful of the very narrow therapeutic window afforded by
the tip's thermal interactions with the tissue. When radiant
optical and thermal energy is applied to biological tissues with a
"hot tip", the temperature of the contact area rises immediately.
At 45.degree. C., the tissue becomes hyperthermic. At 50.degree.
C., there is reduction in cellular enzyme activity and some cell
immobility. At 60.degree. C., proteins denature, and there is
evidence of coagulation. At 80.degree. C., cell membranes become
permeable, and at 100.degree. C., water and tissue begin to
vaporize.
[0058] If the temperature increases for 2 to 5 seconds beyond
80.degree. C., there will be irreversible damage to the mucosa,
bone, periodontal, and dental structures. These considerations are
of direct importance for contact tip procedures such as a
gingivectomy, gingivoplasty, frenectomy, incision and drainage,
removal of a fibroma, and periodontal sulcular currettage (see
Rossman, J. Periodontol. 73:1231-1239 (2002)).
[0059] According to the invention, the optical fiber emitting
optical energy in the near infrared spectral range is contacted
with at least a portion of the tissue previously stained with the
chromophore dye. According to the invention, the tissue should be
irradiated for a therapeutically effective amount of time in a
moving pattern. The expression "therapeutically effective amount of
time" and "therapeutically effective time window" is used to denote
treatments for periods of time effective to achieve the therapeutic
result sought. Because of the immediacy of the result sought (i.e.,
the formation of the coagulum from the biofilm) the practitioner is
able to tailor and ascertain therapeutically effective times
visually. The invention therefore provides a method to tailor the
administration/treatment to the particular exigencies specific to a
given patient. As illustrated in the following examples,
therapeutically effective amounts may be easily determined for
example empirically by starting with a relative short time period
and by step-wise increments with concurrent evaluation of
beneficial effects.
[0060] Prior to the invention, the objective when using a laser
with a "hot tip" in the periodontal pocket, was to generate
sufficient thermal energy at the tip to cause immediate tissue
vaporization and ablation limited to the inflamed epithelial
periodontal lining, otherwise known as sulcular curettage. To
accomplish it, the tissue must be rapidly heated to several hundred
degrees Celsius at the contact point of the tip. A diode or Nd:YAG
laser can readily accomplish this when used in the contact mode. As
the optical and thermal energy (of the secondary blackbody
emission) is directly transferred to the tissue in the vicinity of
the tip, a poorly controlled vaporization of sulcular epithelium
ensues.
[0061] During these procedures, it is imperative to keep treatment
contact intervals in any one spot relatively short (1 second),
since any extra exposure of periodontal tissues (including tooth
and bone) the tip will damage these peripheral tissues. The will
occur because the heat will be transferred deeper into the tissues
via heat conduction, and will not be rapidly dissipated by the
tissues if there are any prolonged periods of contact. If the
contact exposure time is too long (more than 2-3 seconds in one
area), the ability of the tissues to dissipate heat is overcome,
and irreversible damage occurs to non-target tissues.
[0062] As stated, in the contact mode a large percentage of the
near-infrared photons (the primary emission of the laser) are
absorbed by the blackbody tip and carbonized coagulum. As a result,
the emission, and hence penetration and absorption of these primary
(single wavelength) infrared photons generated from the laser, are
greatly decreased. Therefore, the danger to peripheral tissues
(around the periodontal pocket) is directly dependent on the
exposure time of the "hot tip" to the tissue and the heat
conduction from the tip to the tissue. These greatly decreased
primary emissions of the laser through a carbonized tip were
studied in detail by Grant et al., Lasers in Surgery and Medicine
21:65-71 (1997), as they specifically looked at the "fiber
interaction" during contact laser surgery. Grant showed that with
tissue deposits at the tip of the fiber absorbing larger amounts of
laser light, immediate carbonization occurs. The carbonization of
the fiber tip leads to an increase in temperature, and this can
result in significant damage to the optical quality of the fiber
(the temperature spikes to greater than 900.degree. C.). Grant also
found that once the carbonization of the tip occurs, the tip no
longer functions as an adequate forward light guide (i.e., there is
now limited primary photon forward progression of laser energy).
The laser will no longer adequately photocoagulate, but rather it
incises and cauterizes the tissue because of the intense heat at
the tip. While the hot tip described in Grant et al. has direct and
unimpeded energy effecting the tissues within the sulcus, the
current invention's hot tip is exploited by making it possible to
coagulate the target biofilm in total (because of the heat
sink/chromophore), while at the same time the peripheral tissues
are left protected.
[0063] It is also important to remember that the silica portion of
a typical optical fiber consists of two regions--the core that runs
through the center of the strand, and the cladding that surrounds
the core. The cladding has a different refractive index than the
core, and acts as a mirror that causes the laser light to reflect
back into the core during its transmission through the fiber.
Furthermore, longer lasing times and higher power drastically
reduce the forward power transmission of the laser light, as the
fiber tip sustains more and more heat induced damage. When a 360
micron fiber (with a 830 nm diode laser at 3 watts CW, with a laser
power meter) was tested, it was found that an immediate 30% loss of
forward power transmission is observed with fiber carbonization
from tissue detritus. Further power loss was observed as lasing
time continued and tissue debris accumulated.
[0064] Willems et al., Lasers in Surgery and Medicine 28(4):324-329
(2001) elucidated this phenomenon in vivo using diode and Nd:YAG
lasers. Conventional fiber tips and coated fiber tips were compared
for ablation efficiency in rabbit cerebral tissue. With the
conventional fiber tips, histology and thermal imaging demonstrated
deleterious effects deep into the tissue. When using the coated
fiber tip, they reported that almost all laser light was
transformed into thermal energy (as the tip carbonized), and
instantly produced ablative temperatures at the tip itself.
Further, they reported that ablation was observed at relatively low
energy and power (1 W for 1 second) with thermal effects restricted
only to the superficial structures. This restriction of thermal
effects to superficial structures can be explained, as the forward
power transmission of the laser light is attenuated when a larger
percentage of the primary emissions of the laser are absorbed by
the tip. As a result, the optical transmission qualities are
damaged. In order to protect deeper tissues, they altered the
distal end of the tip to completely inhibit any forward progression
of primary infrared photons, whereas the present invention utilizes
a chromophore/heat sink to both target the biofilm and protect the
surrounding tissues. Also of significance, as the quality of the
fiber transmission diminishes as a result of damage to the tip, the
energy, focus, and homogeneity of the energy being transmitted from
the tip is affected. The primary energy that is still available for
forward power transmission out of the tip is far less efficient for
tissue penetration and photocoagulation. This inventor has
developed a novel system to exploit these quantum realities, with
biofilm targeting technology.
[0065] Furthermore, (Proebstle et al., Dermatol. Surg. 28:596-600
(2002)) in a study evaluating the thermal damage to the interior
walls of veins with 600 .mu.m fibers in endovenous laser treatment,
found no major differences could be detected between the three
diode laser wavelengths of 810 nm, 940 nm, and 980 nm. The laser
wavelength interaction with the blood immediately transferred the
optical energy completely into heat at all wavelengths, even with
new, uncarbonized fibers. In essence, what Proebstle's data
confirms, is that when delivery tip carbonization occurs (now
understood to be a universal event with these lasers), and tip
preferentially absorbed the laser energy causing extremely high
temperature generation and a "hot tip" (all intra-pocket
periodontal and periimplant procedures) any subtle wavelength
differences in the near infrared 800-1100 nm are not critical to
the procedure being performed.
[0066] It is now understood that optical fiber tips used with near
infrared lasers (600 nm-1100 nm) at moderate fluences (about 350 mw
and above) experience heat induced carbonization almost immediately
upon contact with oral tissues and/or blood. The carbonization is
thermally driven, and causes degradation of the forward power
transmission potential from the tip, as the tip absorbs the primary
infrared photons from the laser and becomes red hot and
incandescent. Upon carbonization, this tip can be referred to as a
blackbody emitter of secondary radiation (ultraviolet, visible, and
infrared light), and has a thermal interaction and photobiology
distinctly different from what occurs with clean, uncarbonized
non-contact fibers. It is no longer single primary emitter of
monochromatic laser energy.
[0067] With all visible and infrared light, after the energy of the
photons is absorbed by a chrompohore, it is converted to kinetic
energy within the target molecules (i.e., heat). The energy
transferred may cause damage (e.g., excessive dosimetry). It has
been found that a heat sink is ideally suited in conjunction with
near infrared laser periodontal treatment with secondary quantum
emissions generated from a "hot tip" blackbody radiator. Heat
deposition may be due to local conversion of optical energy from
the laser in the tissue to heat energy, or to heat conduction from
the hot-tip (quantum secondary blackbody emissions) of the naked or
unclad optical silicate delivery fiber within the periodontal or
periimplant pocket.
[0068] With these thermodynamic realities now understood, it is
easily explained that excess power output from the laser, or excess
time in a dental surgical procedure can induce heat related
deleterious effects to the patient and irradiated tissues.
[0069] To accomplish safe and predictable periodontal therapy (and
biofilm coagulation with bacterial cell death) with near infrared
dental diode lasers, the operator must be cognizant of the very
narrow therapeutic window afforded by the lasers thermal
interactions with human tissues.
[0070] To achieve photothermolysis (heat induced death) and live
biofilm coagulation with the near infrared dental laser, a
significant temperature increase must occur for a given amount of
time in the target tissue or tissue area of the periodontal pocket.
From 60.degree. C. to 80.degree. C. is the range of temperature in
the surrounding tissue that must be achieved for short periods of
time, under skilled control and delivery, for the live biofilm
phase shift to occur, and transform from a slimy proteinacious
matrix to a solid coagulum. This must occur for the near infrared
dental laser to be effective at biofilm thermolysis without causing
undue harm to healthy oral tissues.
[0071] As the tip begins to glow (i.e., as it becomes a "hot tip"),
it emits first red, and then orange visible light as is evidenced
by a C.I.E. Chromaticity Map that is overlaid with a blackbody
locus (FIG. 2) (in the 600 nm to 700 nm range). This emission falls
exactly within the absorption band for Methylene Blue. Thus the
biofilm stained therewith selectively absorb the energy emitted by
the hot tip.
[0072] The invention provides a kit for treating an in vivo biofilm
and tissue on a periodontal or periimplant surface including an
optical fiber extending between a proximal end and a distal end.
According to the invention, the proximal end receives optical
energy incident thereon in a near infrared spectral range, and the
optical fiber transmits the received optical energy to the distal
end emitting optical energy in the predetermined spectral range.
The terms and specific features of the elements in the kits of the
invention are as described above in connection with the methods of
the invention. In certain embodiments, the predetermined spectral
range is from about 600 to about 700 nm.
[0073] The distal end of the optical fiber may be made of silica,
zircon glass or other compatible material capable of generating a
"hot tip" (e.g., fused silica). For each different procedure and
patient, the old blackbody tip is cleaved off and the fiber
sterilized to prepare the fiber for a new patient.
[0074] Kits according to the invention further include a reservoir
to store a chromophore dye having an absorption spectrum in the
spectral range of a blackbody radiator described herein the
invention. In certain embodiments, the reservoir includes an
applicator assembly for the selective application of the
chromophore dye to the biofilm and tissue on the periodontal or
periimplant surface (such as for example a small fiber brush, or a
syringe, see FIG. 5 exemplifying a syringe and a reservoir
containing a 0.1% MB solution).
[0075] Kits according to the invention may further comprise an
optical energy source for generating optical energy in the near
infrared spectrum, and an associated coupling assembly for coupling
the optical energy to the proximal end of an optical fiber. In
certain embodiments, the optical energy generated is coherent. In
other embodiments, the optical energy source is a diode laser
operating at 350-1200 mW generating energy having a wavelength of
about 830 nm.
[0076] The kits according to this aspect of the invention may also
include heat sink moieties as discussed infra. Accordingly, some
kits include a chromophore dye such as MB. The heat sink moieities
of the invention may be provided in a reservoir adapted to store a
chromophore dye characterized by an absorption spectrum in the
spectral range of a blackbody radiator described herein the
invention. The reservoir may further include an applicator assembly
adapted to effect selective application of the chromophore dye to a
region of the biofilm on a periodontal or periimplant surface. The
chromophore dye may be pre-packed in a reservoir with a light foil
cover. In some embodiments, the practitioner pushes on the brush,
breaks the foil, and wets the bristles with the dye (e.g., MB) for
topical deposition to the area of the oral cavity to be treated.
These areas include the periodontal pocket, the periimplant site,
and or any other site in the oral cavity requiring treatment
according to the invention.
[0077] The laser energy may be delivered through a commercially
available surgical fiber from 200 microns to 1000 microns in
diameter with an unclad and cleaved distal end, in contact or
non-contact mode (FIG. 3A). The laser energy is delivered from a
solid state continuous wave or pulsed dental diode or Nd:YAG laser
ranging from 800 nm to 1064 nm to make use of the secondary
emission blackbody reaction with the hot tip and the absorption
peak in MB. The laser energy is delivered from 1 to 120 seconds per
area in a moving pattern that never stays stationary for more than
2-3 seconds. The energy production from the laser at the distal end
of the conical tip fiber is no less than 200 mW and no more than
4000 mW.
[0078] When a lasers output powers (W) and beam area (cm.sup.2) are
known with a clean cleaved fiber, the remaining parameters of
effective treatment can be calculated to allow the precise dosage
measurement and delivery of energy for effective and safe treatment
to oral tissues. In the periodontal pocket however, with the fiber
tip immediately becoming an incandescent blackbody radiator, the
normal power equations will not reflect the reality of the new
quantum mechanics. Even with the generation of secondary blackbody
emissions, the output power of a laser does not change, and simply
refers to the number of photons emitted at the given wavelength of
the laser.
[0079] Before the fiber touches tissue, the power density of the
laser will measures the potential thermal effect of laser photons
at a treatment irradiation area. Power Density is a function of
Laser Output Power and Beam area (again with a clean cleaved
fiber), and is calculated with the following equations:
Power Density = ( W / cm 2 ) = Laser Output Power Beam Diameter (
cm ) 2 ( 1 ) ##EQU00001##
[0080] Hence, the total photonic energy delivered into the oral
tissues by a dental near-infrared laser (before the clean tip
touches the tissues) is measured in Joules, and is calculated as
follows:
Total Energy(Joules)=Laser Output Power(W).times.Time(Secs) (2)
[0081] Once the tip touches biofilm or tissue and becomes an
incandescent blackbody radiator, approximately 70+% of the output
power of the laser is converted to local heat, it no longer emits
significant monochromatic light (i.e., because the carbonized tip
is absorbing it) and it now produces light in a continuous
distribution of wavelengths (continuous spectrum) and in all
directions. Hence, there is no "spot size" available for a "power
density" equation. For this reason, the total energy equation (2),
will be used.
[0082] In some applications, it may be desirable to broaden or
increase the effective surface area from which incandescent light
(that falls within the absorption band of the dyed biofilm) is
emitted, for example by causing incandescent radiation to be
emitted from areas of the optical fiber other than the narrow
distal tip alone. In this way, an increased amount of incandescent
light may be available to be absorbed by the stained biofilm, at a
faster speed, thereby more effectively accomplishing the desired
thermolysis of the dyed biofilm in the tissue treated.
[0083] In some embodiments, such an increase in the effective
surface area from which incandescent light is emitted is
accomplished by causing at least some light propagating from the
distal tip (toward the proximal end) to be directed onto the dyed
biofilm or other target tissue, through the lateral walls of the
optical fiber. As explained above, not all of the incandescent
radiation (or "secondary quantum emission") that is generated from
the carbonized fiber optic tip is transmitted onto the target
tissue (e.g. the biofilm stained with Methylene Blue). Rather, some
of the incandescent radiation generated from the glowing carbonized
tip of the fiber propagates in "reverse" through the fiber optic
core, from the distal end toward the proximal end of the optical
fiber. In some embodiments, this back-propagating incandescent
radiation can be directed onto target tissue, as described
below.
[0084] In the embodiment illustrated in FIG. 7, the effective
surface area from which incandescent light is emitted is increased,
by modifying the surface geometry of the distal end of the optical
fiber in such a way that at least some of the back-propagating
incandescent radiation can be diverted and re-directed toward
target tissue by transmission through the lateral walls of the
optical fiber. Specifically, the surface geometry of the lateral
walls of at least a portion of the distal end of the optical fiber
is modified, for example by etching, roughening, frosting, or other
methods well known in the art, so that at least some of the
back-propagating radiation no longer undergoes total internal
reflection at the boundary between the core 30 and the cladding 35
of the optical fiber, but rather is transmitted through the lateral
walls and towards off-axis target tissue. When such transmitted
light has sufficient energy density, then the sidewalls become
carbonized, as did the distal tip. Again, at sufficient energy
density, the carbonized lateral surfaces generate incandescent
radiation, which interacts with the dyed biofilm to effect
thermolysis of the biofilm.
[0085] FIG. 7 illustrates an exaggerated saw-tooth geometry of a
surface of the lateral walls of a portion of the distal end of the
optical fiber, modified in the manner described above. FIG. 7 is
not drawn to scale, and is meant to provide an exemplary schematic
rendition of the etched or otherwise modified surface geometry of
the optical fiber lateral walls, which is illustrative of the
principles explained above.
[0086] As well known, optical fibers are configured so as to guide
light from one end of the optical fiber to the other end, by
causing the light to undergo total internal reflection at the
boundary between the core and the cladding of the optical fiber, so
that light is guided through the optical fiber core, from one end
of the fiber to the other. The differences between the indices of
refraction of the optical fiber core and the optical fiber are such
that, for a smooth unmodified surface geometry of the (typically
cylindrical) optical fiber, the light traveling through the core is
reflected off the cladding glass and stays within the core, so that
the fiber core acts as a waveguide for the transmitted light.
[0087] As seen in FIG. 7, in one embodiment the smooth surface of
the lateral walls of a portion of the distal end is modified or
etched in such a way that the surface is no longer smooth, but
jagged or serrated. In particular, the etching or serrating of the
surface of the optical fiber walls is performed in such a way that
the angle of incidence, at which the back-propagating light is
incident upon the boundary, is no longer greater than the critical
angle, thereby preventing the back-scattering light from undergoing
total internal reflection. In this way, back-propagating
incandescent light which, in the absence of the modification or
etching of the fiber optic wall surface, would have bounced off the
cladding and would have stayed within the core to reverse-propagate
towards the proximal end of the optical fiber, no longer undergoes
total internal reflection at the core-cladding boundary. Rather,
the back-propagating radiation incident upon the core-cladding
boundary is refracted, so that at least a portion of the
back-scattered radiation incident upon the boundary is transmitted
through the cladding glass forming the optical fiber wall, and is
directed onto the dyed film.
EXAMPLES
[0088] The laser used to exemplify the invention was a 830 nm diode
laser with a power output of between 800 mW-1200 mW in the
Continuous Wave mode of operation, through a 600 micron silica
laser delivery fiber. The live human patients (in vivo) all
presented with some advanced state of periodontal or periimplant
disease and/or active infection. Presented below are data for two
representative patients. Notably, the procedure has been performed
on 50 patients in the last 24 months. In this time period both the
chromophore Methylene Blue and Toludine Blue have been used with
successful outcomes, specifically using this invention at the given
parameters, in periodontal and periimplant pockets and
infections.
[0089] The following examples are intended to further illustrate
certain preferred embodiments of the invention and are not limiting
in nature. Those skilled in the art will recognize, or be able to
ascertain, using no more than routine experimentation, numerous
equivalents to the specific substances and procedures described
herein. Reference is made hereinafter in detail to specific
embodiments of the invention. While the invention will be described
in conjunction with these specific embodiments, it will be
understood that it is not intended to limit the invention to such
specific embodiments. On the contrary, it is intended to cover
alternatives, modifications, and equivalents as may be included
within the spirit and scope of the invention as defined by the
appended claims. In the instant description, numerous specific
details are set forth in order to provide a thorough understanding
of the present invention. The present invention may be practiced
without some or all of these specific details. In other instances,
well known process operations have not been described in detail, in
order not to unnecessarily obscure the present invention.
Example 1
Treatment of a Recalcitrant 10 Mm Periodontal Pocket
[0090] Presented as a healthy 24 year old with a recalcitrant 10 mm
periodontal pocket on the facial aspect of the maxillary canine
(tooth #6) after a regular dental cleaning and scaling. In a
minimally invasive procedure, the patient was anesthetized with
xylocaine, and the periodontal pocket was infused with 0.1% MB
solution via a small bristled brush that easily fits into the
volume of the pocket. The MB solution was left for approximately 2
minutes in the area, and then surface irrigation of H.sub.2O was
applied.
[0091] A 600 nm silica fiber connected to a 830 nm dental diode
laser (sold by Lumenis Technologies, Yokneam, Israel) was then
activated at 1000 mW and the fiber was placed into the periodontal
pocket, where it immediately came in contact with biofilm, tissue,
and blood products. The tip of the fiber immediately carbonized,
and became incandescent. The fiber (with the secondary quantum
emissions emanating from the carbonized tip), was then moved around
the three dimensional area of the periodontal pocket for a period
of 30 to 45 seconds in rapid movements, never staying in one direct
area for more than 1 second at a time. The area was then scaled
with traditional gracey periodontal scalers (sold by Hu-Friedy
Chicago, Ill.), and then irrigated with copious water. The patient
was sent home with administration of 600 mg of Ibuprophen (sold by
Wyeth, Madison, N.J.) analgesic given chair-side, and no
antibiotics.
[0092] Results: At eight days post-op, the periodontal pocket was
completely closed, with tissue attachment present that would
"blanch" under pressure from a periodontal probe. The area
presented with pink and healthy gingival surrounding the previous
pocket area. At six weeks, and then four months, the area was only
probing at 3 mm (gingival and periodontal health) and the patient
was placed on regular six month recall.
Example 2
Treatment of Infected Periimplant Tissue
[0093] Presented as a brittle diabetic with an infected titanium
implant and a fistula draining the infection. Radiographic
appearance detailed 8 mm of lost bone, and generalized radiolucency
around the medial half of the implant. Three different antibiotic
regimens failed to cure the patient of the infection. The area was
surgically opened with a conventional trapezoidal shaped flap, and
the infection and biofilm effected area was bathed in a 0.1% MB
solution (sold by Vista Dental Products, Racine, Wis.) for
approximately 2 minutes. The area was then irrigated with copious
H.sub.2O, leaving the targeted biofilm behind, and washing away
excess stain. A 600 nm silica fiber connected to an 830 nm dental
diode laser was then activated at 1200 mW and the fiber was placed
in contact with biofilm and blood products and immediately
carbonized. The fiber, with the secondary quantum emissions
emanating from the carbonized tip were then moved around the near
proximity to the area and implant (within 1/2 mm) for a period of
60 to 90 seconds, never staying in one direct area for more than 2
seconds at a time. The area was then scaled with plastic implant
scalers, and irrigated with copious water and sutured closed. The
patient was given a 5 day regimen of 500 mg Amoxicillin, (sold by
Ranbaxy Pharmaceuticals, Jacksonville, Fla.) three times/day.
[0094] Result: At three weeks post-op, the area was completely free
of infection with pink and healthy gingival surrounding the area.
At four months, a fixed porcelain to gold bridge was cemented onto
the implant. At 9 months, the area was still infection free.
* * * * *