Note: Descriptions are shown in the official language in which they were submitted.
PATENT APPLICATION
ANALGESIC NOSE PLUGS
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part application of U.S.
Patent Application
No. 16/345,452, entitled "Hemostatic Nose Plugs", filed on April 26, 2019,
which is a 371
National Stage of International Application No. PCT/CA2017/051285, entitled
"Hemostatic Nose
Plugs", filed on October 27, 2017, which claims priority to and the benefit of
U.S. Provisional
Patent Application No. 62/413,527, entitled "Hemostatic Nose Plugs", filed on
October 27, 2016,
and the specification and claims thereof are incorporated herein by reference.
TECHNICAL FIELD
[0002] This disclosure generally relates to non-invasive techniques for
delivering
medicaments. In particular, the disclosure relates to hemostatic-coated nose
plugs configured to
deliver medicaments through intranasal pathways.
BACKGROUND
[0003] Intranasal pathways may be used to deliver certain medicaments to
the
bloodstream. In more detail, the nasal cavity is covered by a thin mucosa that
is well-
vascularized. Medicaments administered via the intranasal pathways thus need
only transfer
across a single epithelial cell layer for systematic blood circulation. As
well, because the
medicaments are administered via the intranasal pathways, they avoid the first
pass effect,
which simplifies the determination of their dosages. In some cases, the
medicaments may also
avoid the blood brain barrier.
[0004] Medicaments designed for intranasal delivery are typically
incorporated into
nasal sprays. The nasal sprays produce a mist of a solution containing the
medicament that
coats the nostril and/or nasal passage. The medicament is then transferred
across the mucosa
and into the bloodstream. However, as will be appreciated, nasal sprays are
not well suited for
prolonged delivery of a medicament, as the coating provided by the mist is
quickly degraded by
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Date Recue/Date Received 2021-09-24
a user's breathing. As a result, several applications may be necessary.
Further, it may therefore
also be difficult to determine if an appropriate dose has been delivered.
[0005] One approach to addressing the limitations of medicament delivery
via nasal
spray has been to coat a cotton ball or the like in a medicament and insert
the coated cotton ball
into a patient's nose. The coated cotton ball contacts the inside of the
nostril and/or nasal
passage to deliver the medicament thereto. However, as will be appreciated, it
is also difficult to
determine the dosage administered to a patient, as it may be challenging to
determine how
much of the medicament is coated onto the cotton ball as well as the surface
area of the cotton
ball that is in contact with the patient's nostril and/or nasal cavity to
deliver the medicament
thereto.
BRIEF SUMMARY
[0006] The present disclosure relates to analgesic nose plugs for treating
and/or
preventing pain and optionally other ailments.
[0007] According to one example embodiment of the present disclosure, there
is
provided a deformable analgesic nose plug. The deformable analgesic nose plug
comprises a
deformable core material comprising a multi-phasic core material. The multi-
phasic core
material has a first phase characterized by a solid or a semi-solid structure
at a temperature of
35 C or less and a second phase characterized by liquefaction at a
temperature of 37 C or
greater. The deformable analgesic nose plug also comprises one or more
analgesic
compounds. In one aspect, the nose plug has a tapered distal end for insertion
into a nostril and
a proximal end whereby the nose plug is inserted into the nostril.
[0008] The analgesic nose plugs of the present disclosure may provide a
number of
advantages. For example, the nose plugs may provide rapid relief of pain such
as head, face,
and/or neck pain. In more detail, medicaments administered intranasally may be
transferred
directly to the blood stream via the mucosa. However, most over-the-counter
treatments
available are for administration in the form of pills or tablets. Such
treatments may, in contrast,
take up to an hour to provide relief of pain or other related symptoms,
depending on when the
patient last ate, how much they ate, and other such events. The nose plugs of
the present
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disclosure are not affected by such factors and may consistently provide rapid
administration of
medicaments and thus rapid relief of pain.
[0009] Another advantage of the nose plugs of the present disclosure is
that they may
deliver medicaments non-invasively. As described above, treatments
administered by way of
pills or tablets may take a significant amount of time to take effect. One
alternative used by
medical practitioners is to administer the treatment intravenously by way of a
needle, which
affords a more rapid delivery of the medicament than the pills or tablets.
However, needles are
uncomfortable and may be painful. The nose plugs of the present disclosure, in
contrast, may
provide similar delivery of medicaments to the bloodstream while also avoiding
the discomfort
and pain caused by needles.
[0010] Yet another advantage of the nose plugs of the present disclosure is
that they
may provide prolonged administration of medicaments to a patient. In more
detail, the nose
plugs are inserted into a patient's nose and allowed to deliver medicaments
for an extended
period of time, which may be particularly useful for anesthetics.
Conventionally, for prolonged
administration, medicaments are administered intravenously, which has a number
of
disadvantages such as those described above.
[0011] Further advantages will be discussed below and will be readily
apparent to those
of ordinary skill in the art upon reading the present disclosure.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] The accompanying drawings, which are incorporated into and form a
part of the
specification, illustrate one or more embodiments of the present invention
and, together with the
description, serve to explain the principles of the invention. The drawings
are only for the
purpose of illustrating one or more embodiments of the invention and are not
to be construed as
limiting the invention. The embodiments of the present disclosure will be
described with
reference to the following drawings in which:
[0013] Fig. 1A is a side view of the nose plug according to one embodiment
of the
present disclosure, and Fig. 1B is a cross-sectional view of the nose plug;
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[0014] Fig. 2 is a cross -sectional side view of another embodiment of
another nose plug
according to of the present disclosure;
[0015] Fig. 3 is a cross-sectional side view of another embodiment of
another nose plug
according to the present disclosure; and
[0016] Fig. 4 is a cross-sectional side view of another embodiment of
another nose plug
according to the present disclosure.
DETAILED DESCRIPTION
[0017] Some embodiments of the present disclosure generally pertain to nose
plugs
having hemostatic coatings thereon for affecting immediate cessation of
nosebleeds upon
insertion of the nose plugs into nasal cavities. According to one aspect, the
present nose plugs
comprise a core material for receiving and supporting thereon a coating
comprising a compound
with hemostatic properties. According to another aspect, each of the present
nose plugs may
additionally comprise an applicator stick engaged with the core material.
Alternatively, each of
the present nose plugs may comprise a pliable material engaged with the core
material wherein
a portion of the pliable material extends outward from the core material.
[0018] As used herein, "nose plug" refers to a device to be inserted into a
nostril. The
nose plugs generally sized such that, when inserted into the nostril, the nose
plug contacts the
inner surfaces of the nostril in order to maintain its position therein.
[0019] As used herein, the term "core material" refers to the material or
materials that
form the body of the nose plugs of the present disclosure. The core material
is deformable in
that it is capable of being reshaped, which facilitates the insertion of the
nose plugs into nostrils
of different sizes.
[0020] An embodiment of a nose plug 10 according to the present disclosure
is shown in
Figs. 1A and 1B and comprises a multi-phasic core material 25 that has been
coated with a
hemostatic composition 20.
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[0021] A suitable multi-phasic core material 25 may be formed from a
mixture of
materials that are solids or semi-solids at temperatures lower than about 36
C (i.e., a first
phase) and that liquefy at a temperature of 37 C or higher (i.e., a second
phase). Examples of
suitable mixtures of materials for preparing the multi-phasic core material 25
include of two or
more of cocoa butter, polyethylene glycols, hydrogels, glycerin,
polyglycolysed glycerides, and
glycerinated gelatin. Suitable polyglycolysed glycerides include but are not
limited to arachidic
acid, lauric acid, myristic acid, aleic acid, palmitic acid, and steric acid.
The core material 25
may additionally comprise an excipient exemplified by monodecanoyl-glycerol,
monolauroyl-
glycerol, fatty acid triglycerides, thylene glycol, triethylene glycol,
propylene glycol, butylene
glycols, 1,2-propylene glycol, and the like. The multi-phasic core material 25
may additionally
comprise a lubricant exemplified by mineral oil, vegetable oil, polyisobutene,
polyalkyleglycol,
polyolefin, diester, polymerester, vegetable stearin, magnesium stearate,
hydrogenated
vegetable oils, cocoa butter, theobroma oil, hydrogenated corn oil, palm oil,
palm kernel oil,
coconut oil, stearic acid, and the like. The multi-phasic core material 25 may
additionally
comprise an emollient exemplified by salicylic acid, ammonium lactate, urea,
dimenticone, and
the like.
[0022] The multi-phasic core material may be prepared by mixing together
the selected
materials in heated water, for example, at a temperature from a range of 40 C
to 90 C and
anywhere therebetween, and then pouring the mixture into molds for curing and
forming. One
example of a suitable mixture of material for the multi-phasic core is about
14% gelatin plus
about 70% glycerol plus about 16% water. Another example of a suitable mixture
is about 33%
PEG 4000 plus about 47% PEG 6000 plus about 20 % water. Suitable molds for
forming the
multi-phasic core material into nose plugs include metal molds, flexible
rubber molds, silicone
molds, and the like. Alternatively, the multi-phasic core material may be
formed into the nose
plug 10 using a suppository-manufacturing device, which are known in the art.
Each nose plug
of the present disclosure generally comprises about 0.5 g, about 0.6 g, about
0.7 g, about 0.8 g,
about 0.9 g, about 1.0 g, about 1.1 g, about 1.2 g, about 1.3 g, about 1.4 g,
about 1.5 g of
material and therebetween. Particularly suitable is about 1.0 g of core
material.
[0023] The nose plugs of the present disclosure generally have an elongate
cylindrical
shape with a tapered conical distal end 12 (i.e., the end that is inserted
into a nostril). Such
shapes are commonly referred to as bullet-shaped or torpedo-shaped. It is
optional for the distal
end 12 of the nose plugs 10 to have a frusticonical taper terminating with a
rounded end. The
Date Recue/Date Received 2021-09-24
proximal end 14 of a nose plug 10 of the present disclosure, may be flat.
Alternatively, the
proximal end of the nose plug may be concave. Alternatively, the proximal end
of the nose plug
may be convex. The diameter of the multi-phasic core material of the nose
plugs 10 may be
selected from a range of about 0.5 cm to about 1.75 cm and therebetween. The
diameter of a
nose plug 10 approximate its proximal end 14 may be same as the diameter of
the central body
portion of the nose plug 10, i.e., the nose plug 10 may have the same diameter
from its proximal
end 14 until the onset of tapering to its distal end 12. Alternatively, the
diameter of a nose plug
according to the present disclosure, may be slightly flared outward
approximate its proximal
end. Alternatively, the diameter of a nose plug according to the present
disclosure, may be
slightly flared outward approximate its proximal end. The length of the multi-
phasic core material
of the nose plugs may be selected from a range of about 1.5 cm to about 3.5 cm
and
therebetween. The multi-phasic nature of the core material makes it deformable
as the present
nose plug is inserted into a nostril so that a large portion of the outer
covering of the nose plug
is in at least partial and preferably full contact with the nasal membranes
lining the nostril.
[0024] After the multi-phasic cores of the nose plugs have been formed and
solidified, a
solution comprising one or more hemostatic compounds is coated onto the outer
surface of the
nose plug cores, for example, by dipping or by spraying or other suitable
coating processes,
after which the coated nasal plugs are dried. Suitable hemostatic compounds
include but are
not limited to ferrous sulfate, ferric sulfate, aluminum sulfate, ammonium
sulfate, aluminum
potassium sulfate, aluminum chloride, tannic acid, zinc chloride, the like,
and mixtures thereof.
Particularly suitable hemostatic compounds are ferrous sulfate, ferric
sulfate, and mixtures
thereof.
[0025] For use to stop a nosebleed, the present nose plug may be taken out
of its
container and simply inserted into the nostril such that some or all of the
elongate outer surface
of the nose plug is in contact with the nasal tissues lining the nostril
and/or nasal passage. The
hemostatic compound in the outer coating of the nose plug will cause cessation
of bleeding at a
capillary source(s) within the nostril and/or nasal passage. Additionally,
because the of the
deformable nature of the multi-phasic core material and the resiliently
compressible substrate,
the present nose plugs will provide a compression pressure onto and about the
bleeding areas
within the nostril and nasal passage. After insertion of the present nose plug
into a nostril, the
core material will slowly liquefy as the nose plug is warmed to body
temperature (i.e., 37 C)
and will slowly flow to the back of the nasal cavity, toward the pharynx from
where it may be spit
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out, or alternatively, pass into the esophagus and moved to the stomach where
it will digested.
Once the nosebleed has stopped, the nose plug can be removed simply by blowing
the nose.
[0026] It is within the scope of the present disclosure to incorporate
components into the
multi-phasic core material if so desired. Suitable components that may be
incorporated including
clotting factors such as thrombin, prothrombin, thromboplastin, fibrinogen,
and the like; antibiotic
compositions such as penicillin, cephalosporin, tetracycline, macrolides, and
the like;
antimicrobial agents such as ivermectin, thymol, benzoic acid, phenolic acid,
sorbic acids,
alcohols, benzethonium chloride, bronopol, butylparaben, cetrimide,
chlorhexidine,
chlorobutanol, chlorocresol, cresol, ethylparaben, imidurea, methylparaben,
phenol,
phenoxyethanol, phenylethyl alcohol, phenylmercuric acetate, phenylmercuric
borate,
phenylmercuric nitrate, potassium sorbate, propylparaben, sodium propionate,
thimerosalaminoclycosides, glycopepetides, macrocodes, quinolones,
streptogramins,
carbapenems, and the like; antihistamines such as chlorpheniramine,
clemastine,
brompheniramine, diphenhydramine, loratadine, cetirizine, fexofenadine,
capsaicin, and the like;
decongestants such as pseudoephedrine, phenylephrine, oxymetazoline,
epinephrine,
xylometazoline, cocaine, and the like; and combinations thereof.
[0027] Other suitable components for incorporation into the multi-phasic
core material
include emollients exemplified by mineral oil, mixtures of mineral oil and
lanolin alcohols, cetyl
alcohol, cetostearyl alcohol, petrolatum, petrolatum and lanolin alcohols,
cetyl esters wax,
cholesterol, glycerin, glyceryl monostearate, isopropyl myristate, isopropyl
palmitate, lecithin,
allyl caproate, althea officinalis extract, arachidyl alcohol, argobase EUC,
butylene glycol,
dicaprylate/dicaprate, acacia, allantoin, carrageenan, cetyl dimethicone,
cyclome hicone, diethyl
succinate, dihydroabietyl behenate, dioctyl adipate, ethyl laurate, ethyl
palmitate, ethyl stearate,
isoamyl laurate, octanoate, PEG-75, lanolin, sorbitan laurate, walnut oil,
wheat germ oil, super
refined almond, super refined sesame, super refined soyabean, octyl palmitate,
caprylic/capric
triglyceride, glyceryl cocoate, and the like. An emollient, if present, is
present in the
compositions described herein in an amount by weight of the composition of
about 1% to about
30%, about 3% to about 25%, or about 5% to about 15%. Illustratively, one or
more emollients
are present in a total amount of about 1% by weight, about 2%, about 3%, about
4%, about 5%,
about 6%, about 7%, about 8%, about 9%, about 10%, about 1 1%, about 12%,
about 13%,
about 14%, about 1 %, about 16%, about 17%, about 18%, about 19%, about 20%,
about 21%,
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about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%,
about 29%,
or about 30%, and therebetween.
[0028] Other suitable components for incorporation into the multi-phasic
core material
include antioxidants exemplified by citric acid, butylated hydroxytoluene
(BHT), ascorbic acid,
glutathione, retinol, a-tocopherol, 8-carotene, a-carotene, ubiquinone,
butylated hydroxyanisole,
ethyl enediaminetetraacetic acid, selenium, zinc, lignan, uric acid, lipoic
acid, N-acetylcysteine,
and the like. An antioxidant, if present, is present in the compositions
described herein in a total
amount selected from the range of about 0.025% to about 1.0% by weight.
[0029] It is optional to insert an applicator stick 30 into the multi-
phasic core material 25
of a nasal plug 10 as it is solidifying in a mold so that about 0.5 cm to
about 1.5 cm of the
applicator stick extends outward from the proximal end of the nasal plug (Fig.
2). The applicator
stick 30 may be a wooden stick or a plastic stick or a polymeric stick, and
the like. Alternatively,
a length of a flexible material exemplified by a string, a cord, and the like,
may be inserted into
the multi-phasic core material of a nasal plug as it is solidifying in a mold
so that a portion of
about 0.5 cm to about 1.5 cm of the flexible material extends outward from the
proximal end of
the nasal plug. It is optional to place one end of a flexible material into
one core material of a
nasal plug as it is solidifying in a cavity of a mold and the other end of the
flexible material into
an adjacent core material in and adjacent cavity of the mold so that after the
multi-phasic core
material has solidified, two nose plugs are joined together by the flexible
material that extends
into both plug cores. Once the nosebleed has stopped, the nose plug can be
removed via
pulling on the applicator stick or the flexible material.
[0030] Another embodiment of a nose plug 50 according to the present
disclosure is
shown in Fig. 3. The nose plug 50 has a core material, a distal end 52, and a
proximal end 54.
The core material comprises a porous resiliently compressible substrate 65
into which has been
imbedded an applicator stick 70 that extends outward from the proximal end 54
of the nose plug
50. The porous resiliently compressible core material 65 is coated with a
selected hemostatic
compound 60. Suitable hemostatic compounds include but are not limited to
ferrous sulfate,
ferric sulfate, aluminum sulfate, ammonium sulfate, aluminum potassium
sulfate, aluminum
chloride, tannic acid, zinc chloride, the like, and mixtures thereof.
Particularly suitable
hemostatic compounds are ferrous sulfate, ferric sulfate, and mixtures
thereof.
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[0031] Suitable porous resiliently compressible substrates include
materials that can be
formed to bullet shapes or torpedo shapes or elliptical shapes or cylindrical
shapes, for example
man-made polymeric sponges, naturally occurring sponges, fluffy cellulosic
materials, cotton,
rolled gauze, the like, and mixtures thereof. The porous core substrate 65 is
coated with a
hemostatic composition 60. Suitable hemostatic compositions include but are
not limited to
ferrous sulfate, ferric sulfate, aluminum sulfate, ammonium sulfate, aluminum
potassium sulfate,
aluminum chloride, tannic acid, zinc chloride, the like, and mixtures thereof.
Particularly suitable
hemostatic compounds are ferrous sulfate, ferric sulfate, and mixtures
thereof. It is optional if so
desired, to infiltrate the porous resiliently compressible substrate 65 with a
multi-phasic core
material prepared as previously described in reference to Figs. 1A and 1B.
[0032] If so desired, the applicator stick 70 may be substituted for with a
length of a
flexible material exemplified by a string, a cord, and the like. It is
optional to place one end of a
flexible material into one porous resiliently compressible core material 65 of
a nasal plug 50 and
the other end of the flexible material into an adjacent porous resiliently
compressible core
material 65 so that after the porous resiliently compressible core materials
65 have been coated
with a hemostatic composition 60, two nose plugs 50 are joined together by the
flexible material
that extends into both plug cores.
[0033] The resiliently compressible nature of the porous substrate 65 makes
it
deformable as the present nose plug is inserted into a nostril so that a large
portion of the outer
covering of the nose plug 50 is in full contact with the nasal membranes
lining the nostril. Once
the nosebleed has stopped, the nose plug 50 can be removed via pulling on the
applicator stick
70 or the flexible material.
[0034] A further embodiment of the present disclosure relates to nose plugs
comprising
one or more compounds for treating and/or preventing pain and optionally other
ailments. One
example embodiment relates to a deformable analgesic nose plug, comprising: a
deformable
core material comprising a multi-phasic core material wherein a first phase of
the multi-phasic
core material is characterized by a solid or a semi-solid structure at a
temperature of 35 C or
less, and wherein a second phase of the multi-phasic core material is
characterized by
liquefaction at a temperature of 37 C or greater; and one or more analgesic
compounds,
wherein the nose plug has a tapered distal end for insertion into a nostril
and a proximal end
whereby the nose plug is inserted into the nostril.
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[0035] Referring to Fig. 4, there is shown an analgesic nose plug 100
according one
embodiment of the present disclosure. The analgesic nose plug 100 comprises a
deformable
core material 125 and an optional outer coating of an analgesic composition
120. As well, the
analgesic nose plug 100 has tapered distal end 112 and a proximal end 114.
There is also
illustrated an optional applicator 130 embedded into the nose plug 100. The
nose plug 100, the
tapered distal end 112 thereof, the proximal end 114 thereof, and the optional
applicator 130
may be configured in the same manner as previously described herein in
relation to the nose
plugs 10, 50, the tapered distal ends 12, 52, the proximal ends 14, 54, and
the applicators 30,
70, respectively.
[0036] The core material 125 of the analgesic nose plug 100 may also be
configured in
the same manner as the core materials 25, 65. For example, the core material
125 may
comprise the previously described multi-phasic core material and/or the porous
resiliently
compressible core material.
[0037] In the illustrated embodiment, the core material 125 is coated with
the analgesic
composition 120. However, in other embodiments, the analgesic composition 120
may be
incorporated into the core material 125. In some embodiments, the analgesic
composition 120 is
both incorporated into the core material 125 and coated thereon. The analgesic
composition
120 comprises one or more analgesic compounds. The one or more analgesic
compounds may
comprise bupivacaine, lidocaine, prilocaine, benzocaine, dibucaine, pramoxine,
phenol,
cocaine, tetracaine, or any combination thereof. It is noted that, in
embodiments where the
analgesic composition 120 is coated onto the core material 125, it may be
coated onto the core
material 125 using the techniques described above. In one aspect, the core
material 125 is
coated using a solution comprising each of the one or more analgesic compounds
in an amount
of about 10 vol. % to about 30 vol. %. In a particular aspect, the solution
may comprise each of
the one or more analgesic compounds in an amount of about 20 vol. %. In
embodiments where
the analgesic composition 120 is incorporated into the core material 125, the
analgesic
composition 120 may be incorporated in a concentration of about 10% to about
30%. In a
particular aspect, the analgesic composition 120 may be incorporated in a
concentration of
about 20%.
[0038] Further, according to some aspects, the analgesic nose plug 100 may
further
comprise one or more additional components. The additional components may be
medicaments
Date Recue/Date Received 2021-09-24
or may be compounds that provide another non-medical benefit. The one or more
additional
components may be incorporated into the core material 125 and/or into a
coating provided on
the core material 125. In embodiments where the analgesic composition 120 is
coated onto the
core material 125, the one or more additional components may be incorporated
into the
analgesic composition 120. In some aspects, the nose plug 100 may comprise one
or more of
the clotting factors, antibiotics, antimicrobial agents, antihistamines,
decongestants, emollients,
and antioxidants described above. The nose plug 100 may also comprise a
corticosteroid such
as hydrocortisone, mometasone, fluticasone, budesonide, betamethasone, and the
like; an anti-
dependency agent such as naloxone, naltrexone, methadone, buprenorphine, and
the like; an
odorant such as menthol, peppermint, salicylate, methyl salicylate, and the
like; or any
combination thereof.
[0039] Suitable packaging for the nose plugs disclosed herein include
blister packages
containing multiple numbers of the present nose plugs wherein each nose plug
is sealed within
a single blister. Such blister packages may contain one nose plug or two nose
plugs or three
nose plugs or four nose plugs or five nose plugs or six nose plugs or seven
nose plugs or eight
nose plugs or more. Such blister packages may then be sealed into a cardboard
container, for
example one blister package per container or two blister packages per
container or three blister
packages per container or four blister packages per container or more.
Alternatively, multiples of
the present nose plugs may be sealed in plastic bags that are then sealed in a
cardboard
container. Alternatively, multiples of the present nose plugs may be sealed
into a plastic bottle
or composite bottle or pressed fiber bottle. The multiples of the present nose
plugs may be
sealed in plastic bags before being sealed in the bottles. It is optional if
so desired, to sterilize
the sealed and packed nose plugs prior to distribution, for example by gamma
ray irradiation.
[0040] Although the invention has been described in detail with particular
reference to
these embodiments, other embodiments can achieve the same results. Variations
and
modifications of the present invention will be obvious to those skilled in the
art and it is intended
to cover in the appended claims all such modifications and equivalents. The
entire disclosures
of all references, applications, patents, and publications cited above are
hereby incorporated by
reference
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