As the large group of so-called baby-boomers advances in age, there are increasing demands for effective, non-invasive treatment of vascular diseases or dysfunctions affecting the vascular system. There are also increasing demands for non-invasive cosmetic surgery to repair conditions that have vascular origins.
Venous insufficiency is a very common condition resulting from decreased blood flow from the leg veins up to the heart, with pooling of blood in the veins. Normally, one-way valves in the veins keep blood flowing toward the heart, against the force of gravity. When the valves become weak and do not close properly, they allow blood to flow backward, a condition called reflux. The blood collects in the veins and they enlarge.
Veins that have lost their valve effectiveness, become elongated, rope-like, bulged, and thickened. These enlarged, swollen vessels are known as varicose veins and are a direct result of increased pressure from reflux. Varicose veins are distinguished from reticular veins (blue veins) and telangiectasias (spider veins), which also involve valvular insufficiency, by the size and location of the veins.
A common cause of varicose veins in the legs is reflux in a leg and thigh vein called the great saphenous vein, which leads to visible pooling close to the skin, called varicose veins. The reflux in the great saphenous vein can also lead to reticular veins (blue veins) and telangiectasias (spider veins). Besides cosmetic problems, varicose veins are often painful, especially when standing or walking. They often itch, and scratching them can cause ulcers.
By closing a section of the great saphenous vein leading to the varicose or spider veins, the twisted and varicosed branch veins shrink and improve in appearance. Once the diseased vein is closed, other healthy veins take over to carry blood from the leg, re-establishing normal flow.
Non-surgical treatments for an incompetent saphenous vein include sclerotherapy. Sclerotherapy involves the injection of a solution into the vein that causes the vein walls to swell, stick together, and seal shut. This stops the flow of blood and the vein turns into scar tissue. Microsclerotherapy uses special solutions and injection techniques that can increase the success rate for removal of smaller spider veins. Ultrasound-guided sclerotherapy involves an interventional radiologist passing a thin tube called a catheter into the vein using ultrasound guidance and injecting substance that causes the veins to scar and close, rerouting the blood to healthier veins. The affected vein forms a knot of scar tissue that is absorbed by the body over time.
Sclerotherapy involves tedious, hard to learn injection techniques. It can lead to side effects like stinging or painful cramps where the injection was made, or temporary red raised patches of skin, or skin sores, or bruises. The treated vein can also become inflamed or develop lumps of clotted blood. Applying heat and taking aspirin or antibiotics can relieve inflammation. Lumps of coagulated blood can be drained.
Laser surgery can be used to treat varicose and spider veins in the legs. Laser surgery sends very strong bursts of light onto the vein, which makes the vein slowly fade and disappear. Laser surgery is more appealing to some patients because it does not use needles or incisions. Still, when the laser hits the skin, the patient can feel a heat sensation that can be quite painful. Laser surgery can cause redness or swelling of the skin, and can cause burns and scars. Depending on the severity of the veins, two to five treatments (15 to 20 minutes each) are generally needed to remove veins in the legs. Moreover, for veins larger than 3 mm, laser therapy is not very practical. Furthermore, the capital cost for purchasing trans-dermal lasers can be quite high, making the treatment relatively costly.
Minimally invasive vein ablation treatment can also be used to treat varicose veins. This minimally-invasive treatment is an outpatient procedure performed using imaging guidance. After applying local anesthetic to the vein, the interventional radiologist inserts a thin catheter, about the size of a strand of spaghetti, into the vein and guides it up the great saphenous vein in the thigh. Then laser or radiofrequency energy is applied to the inside of the vein. This heats the vein and seals the vein closed.
There is need for devices, systems, methods, and protocols that provide minimally invasive, cost effective, and patient-friendly surgical and/or cosmetic surgical treatment of superficial venous malformations, such as e.g., in the treatment of varicose or spider veins. There is also a need for devices, systems, methods, and protocols that provide minimally invasive, cost effective, and patient-friendly treatment of diseases or dysfunctions in any region of the body that can be readily accessed by treatment agents carried by blood; e.g., cancers like breast and prostrate cancer; ear, nose, and throat conditions; periodontal disease; and diseases of the eye.
The invention provides devices, systems, methods, and protocols that provide minimally invasive, cost effective, and patient-friendly surgical and/or cosmetic surgical treatment of superficial venous malformations, e.g., varicose or spider veins.
The invention also provides devices, systems, methods, and protocols that provide minimally invasive, cost effective, and patient-friendly surgical treatment of diseases or dysfunctions in regions of the body that can be readily accessed by treatment agents carried by blood; e.g., cancers like breast and prostrate cancer; ear, nose, and throat conditions; periodontal disease; and diseases of the eye.
According to one aspect of the invention, the devices, systems and methods distribute a reactive agent at, in, or near an inner wall of a vein. The reactive agent is characterized in that it can be controllably activated by the application of a prescribed form of energy. The devices, systems, and methods activate the reactive agent by applying the prescribed form of energy to activate the reactive agent by use of an intravascular device. The activation of the agent causes localized injury to the inner wall of the vein. The prescribed form of energy can comprise, e.g., electromagnetic radiation, and, more particularly, light energy.
According to another aspect of the invention, the devices, systems, and methods distribute a light-reactive agent at, in, or near an inner wall of a vein. The devices, systems, and methods activate the light-reactive agent by applying light energy using an intravascular device at a wavelength that activates the light-reactive agent to cause localized injury to the inner wall of the vein. The light energy is desirably non-thermal and is generated by a low voltage intravascular photoactivation device, comprising, e.g., one or more light-emitting diodes. In one embodiment, the light-reactive agent comprises LS11 (Talaporfin Sodium) that is administered intravenously. In another embodiment, the light-reactive agent comprises verteporfin that is administered intravenously. Devices, systems, and methods that incorporate this aspect of the invention can treat superficial venous disease, like spider veins.
The devices, systems, and methods improve the quality of patient care. The devices, systems, and methods eliminate side effects such as brusing, burning, and skin discoloration. The devices, systems, and methods do not require tedious, hard to learn injection techniques. They do not require high cost trans-dermal lasers. The devices, systems, and method are usable by a large group of practitioners, such as dermatologists, phlebologists, vascular surgeons, and interventional radiologists.
Although the disclosure hereof is detailed and exact to enable those skilled in the art to practice the invention, the physical embodiments herein disclosed merely exemplify the invention which may be embodied in other specific structures. While the preferred embodiment has been described, the details may be changed without departing from the invention, which is defined by the claims.
As
The great saphenous vein (GSV) is the large superficial vein of the leg and thigh. As
In a number of places in the leg, the superficial saphenous veins and deep veins are linked by perforating veins (or ‘perforators’) (see
All leg veins have delicate valves inside them, which normally function to allow the blood to flow only upwards (towards the heart), or from the superficial veins to the deep veins through the perforating veins. The valves protect against the head of pressure that would otherwise exist in the veins of the legs on standing, which would drive blood downward toward the feet. A valve occurs every five to ten centimeters in the main superficial veins of the legs.
Normally, the valves in the perforating veins allow blood to flow only inwards, from the superficial veins to the deep veins. If the valves stop working properly, then blood is pushed out into the superficial veins when the muscles contract. A superficial vein can become varicose because a perforating vein is allowing blood to flow the wrong way (outwards).
In almost any part of the leg, a perforating vein can develop incompetent valves. This allows blood to be pumped outwards under pressure into superficial veins, causing them to become stretched and varicose. The great saphenous vein and its tributaries are the ones that most often form varicose veins. The small saphenous vein and its tributaries can also become varicose, but it is affected much less often than the great saphenous vein.
The systems, methods, and devices disclosed herein are directed to the distribution of a selected reactive agent at, in, or near an inner wall of a vein feeding a varicose or spider vein, such as incompetent segments of a superficial veins such as the great saphenous vein, small saphenous vein, accessory saphenous vein, and perforators. The selected reactive agent is characterized in that it can be reliably and controllably activating in situ by the application of a prescribed form of energy. Once distributed to the targeted site, the reactive agent can be activated in situ by applying the prescribed form of energy. The activation of the reactive agent causes localized injury to the inner wall of the vein. The prescribed form of energy can comprise, e.g., electromagnetic radiation, and, more particularly, electromagnetic radiation in the wavelength spectrum comprising light energy. The devices and system, and their associated methods of use, are particularly well suited for treating superficial venous diseases, such as varicose veins and spider veins.
Still, it should be appreciated that the disclosed devices and system 10, and their associated methods of use are applicable for use in treating other diseases or dysfunctions elsewhere in the body that are not necessarily related to varicose veins or spider veins or their cause, but are nevertheless capable of treatment by light-reactive agents carried by blood. Other conditions that can be treated by light reactive agents using the system 10 or a form of the system 10 include cancer, e.g., breast or prostrate cancer; conditions of the ear, nose, or throat; periodontal disease; and conditions of the eye or sight (opthalmology).
As
The light reactive agent 14 can comprise any light-reactive drug suited for photodynamic therapy (PDT). PDT is a treatment that uses an agent or drug, also called a photosensitizer or photosensitizing agent, and light energy of a particular selected wavelength. The photosensitizers, which are inert by themselves, bind to proteins found in blood, e.g., lipoproteins. The proteins act as carriers, transporting the photosensitizers to cells targeted for treatment. When exposed to light of the particular wavelength (which varies according to the photosensitizer), the photosensitizer reacts with oxygen. The reaction transforms the oxygen into singlet oxygen and free radicals. The singlet oxygen and free radicals disrupt normal cellular functions and cause cell death.
The light reactive agent 14 can be selected among a group of photosensitizers, depending upon type and location of tissue being treated, as well as the mode contemplated for its introduction into body tissue. Each photosensitizer is activated by light of a specific wavelength. This wavelength determines how far the light can travel into the body. Thus, the physician can select a specific photosensitizer and wavelength(s) of light to treat different areas of the body.
The photosensitizer selected desirably possesses all or some of the following clinically relevant criteria: a commercially available pure chemical; low dark toxicity but strong photocytotoxicity; good selectivity toward target cells; long-wavelength absorbing; rapid removal from the body; and ease of administration through various routes.
Candidate photosensitizers include, but are not limited, to: PHOTOFRIN® (Porfimer sodium—Axcan Pharma, Inc.); FOSCAN® (temoporfin, meta-tetrahydroxyphenylchlorin, mTHPC—Biolitec AG); VISUDYNE® (verteporfin, benzoporphyrin derivative monoacid ring A, BPD-MA—Novartis Pharmaceuticals); LEVULAN® (5-aminolevulinic acid, ALA—DUSA Pharmaceuticals, Inc.); METVIX® (methyl aminolevulinate, MLA or M-ALA—Photocure, ASA); HPPH (2-[1-hexy-loxyethyl]-2-devinyl pyropheophorbide-a, PHOTOCCHLOR—Rosewell Park Cancer Institute); motexafin lutetium (MLu, lutetium(III) texaphyrin, LU-TEX, ANTRIN—Pharmacuclics Inc.); Npe6 (mono-L-aspartyl chlorine e6, taporfin sodium, talaporfin, LS11—Light Science Oncology Inc., Snoqualmie, Wash.); and SnET2 (tin ethyl—etiopurpurin, Sn etiopurpurin, rostaporfin, PHOTREX—Miravant Medical Technologies).
In use, whatever the form, the selected light reactive agent 14 is administered by the system 10 for delivery to a targeted tissue treatment site 64 at, in, or near an inner wall of a vein. In the context of the illustrated embodiment, the targeted tissue site 64 is a sub-dermal region where one or more superficial veins such as the great saphenous vein, small saphenous vein, accessory saphenous vein, and perforators exist that feed or lead to incompetent (varicose or spider) vein segments (this is shown
The form for administration will depend upon the form of the source 12. The light reactive agent 14 can be provided in tablet or capsule form 54 (see
Alternatively, the light reactive agent 14 can be incorporated onto a platform form 58 (see
Alternatively, the light reactive agent 14 can be incorporated into a cream form 56 (see
It has been discovered that an injectable form of Talaporfin Sodium—available from Light Sciences Oncology, Inc as LS11—can be intravenously administered to effectively treat varicose or spider veins using the system 10 shown in
Talaporfin Sodium, together with a special array of light emitting diodes (LEDs), has been tested by Light Sciences Oncology, Inc. in both preclinical and human clinical trials in the United States, Europe and Japan, and has shown efficacy in treating cancer (solid tumors). LS11 material can be activated by shining a LED array at a particular wavelength (664 nm) by a light source into the affected area of tissue.
It has also been discovered that an injectable form of the porphyrin-based photosensitizer called verteporfin—commercially available from QLT, Inc. as VISUDYNE® material (verteporfin for injection)—can be intravenously administered to effectively treat varicose or spider veins using the system 10 shown in
VISUDYNE® material has been used, together with a special laser light, to treat abnormal blood vessel formation in the eye, called age-related macular degeneration (AMD) (which, if untreated, can lead to loss of eyesight). VISUDYNE® material can be activated by shining a pre-calculated dose of light at a particular wavelength (689 nm) by a low-energy laser or light source 12 into the affected area of tissue.
In the context of the illustrated embodiment, where the source 12 comprises an injectable solution of the light reactive agent 14, the device can take the form of a conventional hand-held syringe 18 (as
As
The proximal end region 24 of the elongated shaft 22 includes a handle 28, as
The distal end region 26 of the elongated shaft 22 carries at least one or more light sources 32, as
The light source or sources 32 have a wavelength or a range of wavelengths. The photoactivation device 20 can include means for controlling the intensity or a range of intensities, spot size or a range of spot sizes, and other operating characteristics of the light source or sources 32 that are conducive to activation the light reactive agent 14 in a desired manner. Desirably, the photoactivation device 20 comprises non-thermal light energy generated by a low-voltage power source (not greater than 12 Volts).
In this arrangement, the system 10 includes a power source 34, as
The photoactive device 20 may, alternatively, deliver light through fiber optic cables (e.g., quartz fiber optic cables) and the like through the elongated shaft 22. Alternatively, a fiber optic cable can be inserted through an endoscope or catheter into a targeted internal tissue region (e.g., within a blood vessel or hollow organ) to treat a dysfunction.
Alternatively, as
The light sources 32 can comprise, e.g., lasers, fluorescent, or incandescent lights. The light sources 32 can also comprise light emitting diodes (LED's). LED's can generate high energy light of desired wavelengths and can be assembled in a range of geometry and sizes. The LED's, emitting light in the wave-length(s) that activates the light reactive agent 14. The LED's of a single photoactivation device 20 can be conditioned to deliver multiple wavelengths, so that the photoactivation device 20 can provide a universal platform for different light reactive agents 14. In the illustrated embodiment, where the light reactive agent 14 is LS11, at least one of the wavelengths is 664 nm. Where the light reactive agent 14 is verteporfin, at least one of the wavelengths is 689 nm.
When the reactive agent is activated by another wavelength within the spectrum of electromagnetic energy, e.g., infrared and ultraviolet light, or X-rays and gamma-rays, the source of activating energy comprises a source of the electromagnetic radiation having the other prescribed wavelength.
The light sources 32 can be arranged in an array sized and configured to focus at common point, as
The pattern of light sources 32 can comprise a single linear or curvilinear array (as shown in
As
The distal end region 26 may include one or more steering wires coupled to a controller on the handle 28. Operating the controller, the caregiver can remotely bend or flex the distal end region 26 within the intravascular path to aid its advancement and desired alignment with the targeted tissue site. The distal end region 26 can include one or more radiopaque markers or bands facilitate visualization and alignment of the light sources 32 with the targeted tissue region within the intravascular path.
As
In the illustrated embodiment, every component of the system 10 is contained within the kit 52. Of course, various components can be provided in separate packaging. In this arrangement, the directions 62 still instruct use of the various components separately provided as a system 10.
The directions 62 can, of course vary. The directions may be physically present in the kit 52, but can also be supplied separately. The directions 62 can be embodied in separate instruction manuals, or in video or audio tapes, CD's, and DVD's. The instructions for use can also be available through an internet web page. The directions 62 instruct the practitioner how to use the system 10 to carry out the intended therapeutic treatment. The directions 62 incorporate a method of treatment using the system 10.
As
In the illustrated embodiment, the light reactive agent 14 is to be administered intravenously. In this arrangement, an appropriate injection site 66 is identified, as shown in
As
Typically, VISUDYNE® material is commercially reconstituted in saline or glucose solution at desired concentration of about verteporfin 2 mg/mL. At this concentration, a typical dose for a spider vein region can be in the order of 1 cc to 5 cc, but this dosage will of course depend upon the physiology of the individual, including the size and depth of the target treatment site 64, the skin type of the individual, and the body size of the individual. The dosage can be determined by clinical study by physical measurements and titration, or can be selected empirically based upon general anatomic considerations, or a combination of these and other considerations.
As
Alternatively (as shown in
The rate of delivery is dependent upon the nature and dosage of the light reactive agent 14 as well as the physiology of the individual being treated. It is desirable to avoid discomfort to the individual, and the rate of delivery selected has this as its primary objective.
It is believed that, given the concentration and volume of the VISUDYNE® material being injected in the illustrated embodiment, an injection period of 20 to 30 seconds is acceptable.
A period of time desirably occurs after injection (as the clocks C in FIGS. 11A/B and 12 indicate), to allow the light reactive agent 14 to become systemic. As
The optimal time period to allow systemic distribution of the light reactive agent 14 in this manner to the targeted treatment site 50 following injection can be determined by clinical study by physical measurements, or can be selected empirically based upon general anatomic considerations, or a combination of these and other considerations.
As the systemic distribution of the light reactive agent 14 occurs, the caretaker can gain access to an intravascular path, e.g., by use of a guide sheath, through which the elongated shaft 22 is passed, or by use of a guide wire, over which the elongated shaft 22 is passed. As
As
As
Treatment by the system 10 and method just described intentionally causes injury to the inner vein walls. By controlling the clinically parameters above described (i.e., the dosage, delivery time and rate, operating conditions of the photoactivation device 20, etc.,) the nature of the injury can be tightly controlled and localized.
The initial injury to the vein wall evokes a healing process (see
It should be appreciated that the devices, systems, methods, and protocols that have been described can provide minimally invasive, cost effective, and patient-friendly treatment of diseases or dysfunctions in all regions of the body that can be readily accessed by treatment agents carried by blood; e.g., cancers like breast and prostrate cancer; ear, nose, and throat conditions; periodontal disease; and diseases of the eye.
The foregoing is considered as illustrative only of the principles of the invention. Furthermore, since numerous modifications and changes will readily occur to those skilled in the art, it is not desired to limit the invention to the exact construction and operation shown and described. While the preferred embodiment has been described, the details may be changed without departing from the invention, which is defined by the claims.
This application is a continuation-in-part of co-pending U.S. patent application Ser. No. 11/799,583, filed May 2, 2007 and entitled “Systems and Methods for Treating Superficial Venous Malformations Like Spider Veins,” which is a continuation-in-part of Unites States patent application Ser. No. 11/446,800, filed Jun. 5, 2006 and entitled “Systems and Methods for Treating Superficial Venous Malformations Like Spider Veins” (now U.S. Pat. No. 7,465,312), which claims the benefit of U.S. Provisional Patent Application Ser. No. 60/796,656, filed May 2, 2006, and entitled “Systems and Methods for Treating Superficial Venous Malformations Like Spider Veins,” which are all incorporated herein by reference.
Number | Date | Country | |
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60796656 | May 2006 | US |
Number | Date | Country | |
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Parent | 11799583 | May 2007 | US |
Child | 12378378 | US | |
Parent | 11446800 | Jun 2006 | US |
Child | 11799583 | US |