Patent Application: US-201314379488-A

Abstract:
a system and method are provided for minimally - invasive removal of fat from a target area by injecting the area with a solution of photo - absorbing nanoparticles and irradiating the injected area with a beam of near infrared light . the nir emission wavelength excites the nanoparticles to melt and liquefy fat within the target area so that the liquefied fat can be aspirated from the target area . the nanoparticles may be gold nanorods having aspect ratios selected to produce surface plasmon resonance when irradiated with nir light around 800 nm .

Description:
disclosed herein are a method and system which combine gold nanorods , near infrared light and minor medical procedures to reduce and remove fatty tissue . by injecting a small volume of a solution of gold nanorods into the targeted area , the invention provides for the selective melting of fat and the tightening of skin upon illumination using a low power , biologically benign near infrared ( nir ) laser . fig1 illustrates the process flow for the inventive method , with each process step linked by an arrow to a diagrammatic image of the step as performed on a target area of a patient . the flexibility in the laser diameter , shape and intensity allows precise control over the target area , which may vary from very small , on the order of a few millimeters , to relatively large , e . g ., several centimeters in diameter . in step 102 , the physician administers a subcutaneous injection into the target area of a solution of gold nanorods ( gnrs ) suspended in a sterile , inert liquid , e . g ., distilled water , using a fine syringe . in step 104 , the gnr solution diffuses through the adipose tissue to be targeted immediately after injection , or as soon as practically possible , nir laser light is focused onto the target area ( step 106 ) for a period that may range from a few seconds to several minutes , depending on the area and volume of the targeted fat , and at least for a sufficient period of time to induce surface plasmon resonance within the gnrs . the laser light has a wavelength within the range of 600 nm to 950 nm , preferably within the range of 700 nm to 900 nm , and more preferably about 800 nm . in step 108 , spr is induced , producing localized heating which , in step 110 , causes the solid fat to liquefy . finally , in step 112 , the physician inserts a syringe into the targeted area to aspirate the liquefied fat . a similar procedure may be used to heat and thus stimulate the surrounding skin to minimize sagging after adipose tissue removal . in such a procedure , the gnr solution may be applied directly to the skin or injected intradermally prior to irradiation by the nir laser light . fig2 is a representative schematic diagram of the components of the system 10 of the present invention . the gnrs 8 ( in solution ) are injected into the target tissue 20 using syringe 24 . the gnrs are preferably suitable for in vivo use , for example , a polymer coating can be added for long circulation . the gnr &# 39 ; s should be sterilized and certified endotoxin - free . the nir laser energy 6 from the energy source 14 is directed into delivery device 16 via a delivery channel 18 , which may be a fiber optic , articulated arm , or other appropriate optical waveguide . in preferred embodiments , the nir laser is tunable to allow selection of a wavelength that is optimized for different size gnrs . the laser should preferably have adjustable power to modulate the degree of heating . control system 22 provides a user interface for use by the physician , or assisting nurse or technician , to select the appropriate laser wavelength , intensity , duration and other parameters that may affect the treatment . at the distal end of delivery device 16 is an energy directing means 28 for directing the pulsed energy toward the surface tissue 12 overlying the target tissue ( fat ) 20 . the directing means 28 may be one or more optical elements such as a lens or other focusing element , beam shaping optics , slits , apertures , gratings , an array of lenses and other optics or other focusing configuration , which focuses the beam within the targeted volume of fat containing the gnrs . in a preferred embodiment , the optical elements may include beam expanding lenses to allow adjustment of the beam spread to cover different size target areas . following irradiation of the gnrs in the fatty tissue to liquefy the fat 20 , the liquid is aspirated using syringe 26 that is inserted into the pocket of liquefied fat . the invention further includes a kit for performing selective fat removal in conjunction with an existing nir laser unit . the kit includes the gnrs 8 in solution and syringes 24 and 26 . the syringe for extracting the liquefied fat may be replaced by a fine cannula connected to a vacuum source that is capable of generating suction at the distal end of the cannula sufficient to draw the liquefied fat from the target area and into a collection vessel . the inventive technique is possible because nir light of low power is minimally absorbed by endogenous components in the body , such as skin , water , hemoglobin . furthermore , low power near infrared light does not cause photodamage to tissue . nir light is currently used for imaging using indocyanine green ( icg ), an fda approved imaging agent able to absorb and emit in this region . while skin and adipose tissue do not absorb the nir wavelengths , gnrs do , enabling fine tuning of the spatiotemporal parameters of heating . because the fat is actually liquefied , the inventive method for selective fat removal has the further advantage of being able to use needles or cannulas that are much smaller in diameter ( on the order of 16 or 18 gauge ) than those required for conventional liposuction , thus reducing patient discomfort , minimizing the risk of damage to surrounding tissue , reducing the risk of scarring and infection , and accelerating healing at the site of the procedure . another major improvement over the prior art methods is the duration of treatment . the highly selective and rapid heating produced by the excited gnrs is capable of producing the desired results within minutes , in contrast with the multiple hours required by typical liposuction procedures . to demonstrate the selective photothermal melting of fat , we performed experiments on a ˜ 2 mm layer of butter sandwiched between two slides separated by a silicone spacer small . gold nanorods ( gnrs ) were procured from nanopartz ™, specifically “ ntracker ™ for in vivo therapeutics ” gold nanorods coated in a proprietary dense layer of hydrophilic polymers , with 10 nm axial diameter and 42 nm length . according to information provided by nanopartz , at this aspect ratio , the plasmon absorption peaks are at 817 nm and 512 nm . laser heating was conducted on butter samples with and without gnrs using an unfocused (˜ 2 mm diameter ) 800 nm beam from a ti - sapphire ( 100 fs , 80 mhz ) laser . the gnr - butter samples were prepared from a mixture of 10 μl of 3 × 10 12 gnr / ml with ˜ 50 mg of butter . melting was monitored by visual inspection . the melting point of butter is 32 - 38 ° c . and its specific heat is ˜ 5 joules / g ° c . this means that with the ˜ 2 mm diameter beam at 800 nm at 0 . 45 w power ( 14 w / cm 2 ), the illuminated butter sample should heat at a rate of approximately 2 degrees every second . the input heat and resulting heating rate is likely less in actuality because of absorption of the microscope slide glass . the butter sample used in these experiments shows no absorption in the region of the laser illumination wavelength , 800 nm , as shown in fig3 a and 3b . the primary contribution to absorption is the fatty acids in the milk fat , which absorb in the visible range of the spectrum . the opacity of the sample limits the transmission of light through the butter so the optical density is high , as shown in the plot of fig3 a . if the contribution of the light scattering to the spectrum is removed , the absorption due to the butter can be better visualized , as shown in fig3 b . experiments on a plain butter sample showed that melting does not occur after 3 minutes , shown in the photos of fig4 , and up to 10 minutes , shown in fig5 a , of illumination with a 0 . 45 w laser beam . in the case of the gnr - butter sample under similar experimental conditions , melting of the butter was observed in the area irradiated by the nir laser beam after 2 . 5 minutes of illumination . fig5 b shows the butter before and after irradiation . testing was also performed on bacon samples to compare the heating behavior in fat versus meat . we added 10 μl of 3 × 10 12 gnr / ml in water onto the fatty sections of the bacon and illuminated the treated sections with a ˜ 2 mm diameter 800 nm beam at 2 . 5 w power . melting of the gnr - injected fat was observed after 45 sec in the volume traversed by the laser beam where gnrs were present . illumination was maintained for a total of 1 . 5 min to further melt the fat and determine whether charring can occur when high temperatures are attained . as shown in fig6 a , charring was observed . the melted fat ( grease ) became so hot that it splattered around the fat sample , indicated by the arrows in the figure . control experiments on similarly irradiated non - gnr fat showed no melting ( fig6 b ). after irradiation , the fat had the same appearance as non - irradiated samples . the irradiated meat sections without gnrs were similarly unaffected ( fig6 c ). these results demonstrate the highly selective nature of the heating in the gnr - injected areas of fat versus untreated areas . experiments indicate that a solution of approximately 3 × 10 12 gnr / ml in water would be an effective injectable photothermal agent for melting adipose tissue upon irradiation with a nir laser as a prelude to in - vivo fat removal . for the removal of 50 ml of fat , less than 10 ml of the gnr may be required . at the price of $ 500 per liter of 3 × 10 12 gnr / ml , the method provides an affordable alternative to conventional liposuction approaches . the application of this technology has many secondary benefits in addition to the cosmetic effect of eliminating body fat . for example , illnesses such as diabetes mellitus are directly related to fat storage and obesity . insulin resistance can be eliminated by reducing body fat content . this scientific fact has significant implications on chronic illnesses such as diabetic nephropathy , diabetic retinopathy and coronary heart disease . to date , existing techniques have not exhibited the ability to remove an effective amount of fatty tissue without causing severe damage to adjacent tissue . in addition , during existing procedures , patients are exposed to the potentially dangerous effects of lidocaine toxicity , which is included in current tumescent solutions . the controlled thermal melting of fat protects all other vital structures , reducing post operative pain and , hence , reducing the amount of lidocaine needed in a tumescent solution and avoid life - 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