Method of treatment of atherosclerosis and a balloon catheter for same

[54] METHOD OF TREATMENT OF

ATHEROSCLEROSIS AND A BALLOON
CATHETER FOR SAME

[75] Inventor: James R. Spears, Boston, Mass.

[73] Assignee: The Beth Israel Hospital Association,

Boston, Mass.

[21] Appl. No.: 443,958

[22] Filed: Nov. 23, 1982

[51] Int. CI.' A61B 6/08

[52] U.S. CI 604/21; 604/53;

128/666; 128/303.1; 128/398

[58] Field of Search 604/20, 21, 49-53,

604/96-100; 128/303.1, 303.11, 325, 344, 630, 653, 654, 656, 658, 665, 666, 398

[56] References Cited

U.S. PATENT DOCUMENTS

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3,557,783 1/1971 Castner 604/20

3,661,148 5/2972 Kolin .

4,266,549 5/1981 Kimura 128/303.1

4,315,512 2/1982 Fogarty 604/97

4,323,071 4/1982 Simpson et al 604/53

4,336,809 6/1982 Clark 128/303.1

4,384,584 5/1983 Chen 604/98

OTHER PUBLICATIONS

Aqueous Peroxyoxalate Chemiluminescence, Final Report to the Office of Naval Research, Contract N0O014-77-C-0634, A. Mohan et al., Discovery Research Department, Chemical Research Div., American Cyanamid Company, Bound Brook, NJ, pp. 1-156 (Jan. 1982).

"Atherosclerosis", H. Wolinsky, Cardiovascular Diseases (U.S.A.), vol. XIV, pp. 1218-1222. "The Photodynamic Properties of a Particular Hematoporphyrin Derivative", R. Lipson et al., Archives of Dermatology (U.S.A.), vol. 82, No. 4, pp. 76/508-84/516 (I960).

R. Lipson et al., "Hematoporphyrin Derivative for Detection and Management of Cancer", Cancer (U.S.A.), vol. 20, No. 12, pp. 2255-2257 (Dec. 1967). R. Lipson et al., "The Use of a Derivative of Hematoporphyrin in Tumor Detection", Journal of the Na

tional Cancer Institute (U.S.A.) vol. 26, No. 1, pp. 1-8 (Jan. 1961).

D. Sanderson et al., "Hematoporphyrin as a Diagnostic Tool", (U.S.A.), vol. 30, No. 5, pp. 1368-1372 (Nov. 1972).

Cancer Therapy Abstracts (U.S.A.), 79-0299, T. Dou-
gherty, "Photoradiation in the Treatment of Recurrent
Breast Carcinoma", p. 69 (1979).
Cancer Therapy Abstracts (U.S.A.), 79-0463, T. Sery,
"Photodynamic Killing of Retinoblastoma Cells with
Hematoporphyrin and Light", pp. 160-161 (1979).
Cancer Therapy Abstracts (U.S.A.), 79-2363, J. Moan,
"The Mechanism of Photodynamic Inactivation of
Human Cells in Vitro in the Presence of Haematopor-
phyrin", pp. 735-736 (1979).

F. Gollan et al., "Oxygen Transport of Colloidal Fluorocarbon Suspensions in Asanguineous Rabbits," American Journal of Physiology (U.S.A.), vol. 229, No. 4, pp. 1045-1049 (Oct. 1975).

(Continued on next page.)

Primary Examiner—C. Fred Rosenbaum
Assistant Examiner—Michelle N. Lester
Attorney, Agent, or Firm—Anthony M. Lorusso

[57] ABSTRACT

A method for the treatment of atherosclerosis in a mammal by destruction of atheromatous plaque is disclosed. The disclosed method includes injecting a hematoporphyrin into the mammal for selective uptake into the atheromatous plaque, and delivering light to the diseased vessel so that the light activates the hematoporphyrin for lysis of the plaque. The preferred method utilizes a balloon catheter equipped with flexible optical fibers for transmission of light from an external source for illumination of the interior of the inflated balloon. By inflation of the balloon, the opaque blood between the balloon and the atheromatous plaque is displaced to facilitate activation of the hematoporphyrin. The balloon may be illuminated and inflated and deflated in a cycle responsive to the patient's pulse so as to minimize interference with blood flow.

8 Claims, 2 Drawing Figures

OTHER PUBLICATIONS K. Kanter et al., "Superiority of Perfluorocarbon Cardioplegia Over Blood or Crystalloid Cardioplegia, " Circulation (U.S.A.), vol. 64, Supplement II, pp. II-75-II-80 (Aug. 1981).

"Fluorescence of Experimental Atheromatous Plaques with Hematoporphyrin Derivative", J. Richard Spears,

Juan Serur, Deborah Shropshire and Sven Paulin J. Clin. Invest., 71:395-399 (1983).

"In Vivo Coronary Angioscopy", J. Richard Spears, H. John Marais, Juan Serur, Oleg Pomerantzeff, Robert Geyer, Robert S. Sipzener, Ronald Weintraub, Robert Thurer, Sven Paulin, Richard Gerstin, William Grossman, J. Am. Coll. Cardiol., 1:1311-1:1314 (1983).

1

METHOD OF TREATMENT OF
ATHEROSCLEROSIS AND A BALLOON
CATHETER FOR SAME

5

BACKGROUND OF THE INVENTION

Atherosclerosis is a coronary disease wherein fatty substances (lipids), hereinafter referred to as atheromatous plaques, form deposits in and beneath the intima which is the innermost membrane lining arteries and 10 veins. Atherosclerosis tends to involve large and medium-sized arteries. Most commonly affected are the aorta and the iliac, femoral, coronary, and cerebral arteries. Clinical symptoms occur because the mass of the atherosclerotic plaque reduces blood flow through 15 the involved artery and thereby compromises tissue or organ function distal to it.

Modern treatment of atherosclerosis revolves around highly sophisticated coronary care units. In general, modern medicine follows one of two approaches to the 20 care of patients suffering from atherosclerotic complications: either (1) the diseased vascular segments are replaced with prosthetic or natural grafts, even going as far as heart transplantation or (2) drugs such as antiarrhythmic agents, anticoagulants and plasma lipid lower- 25 ing agents are administered to enable the patient to live with the condition. Neither approach contemplates a cure of the diseased members.

SUMMARY OF THE INVENTION 30

The present invention provides for treatment of a main artery or other blood vessel afflicted with atherosclerosis. The method involves administration of a hematoporphyrin, preferably by intravenous injection, to the mammal to be treated. The invention resides, in 35 part, in the discovery that the hematoporphyrin so administered is selectively absorbed into the atheromatous plaque, with little or no absorption into healthy areas of the arterial wall. Upon illumination of the atheromatous plaque, containing absorbed hematoporphyrin, the 40 hematoporphyrin is activated and destroys the host atheromatous plaque tissue. Illumination of the plaque may be achieved with either one of two different techniques. With one technique, the patient is catheterized with a light-emitting catheter inserted into the diseased 45 artery or other vessel so that the light-emitting portion of the catheter is adjacent the atheromatous plaque. Alternatively, a form of liquid light is injected into the vascular tree such that the liquid light, which mixes freely with blood or a blood replacement, perfuses the 50 diseased artery.

In the preferred embodiment a special light-emitting balloon catheter is employed. The balloon catheter includes an inflatable balloon secured to one end of the catheter tube, for inflation of a gas from a remote 55 source, and optical fibers which extend through the tube lumen for transmission of light from an external light source to the interior of the balloon. Preferably, the light-transmitting optical fibers are optically joined to a light scattering device within the balloon in the 60 form of a hollow, liquid-filled fiber or tube. The liquid filling is selected for optimum transmission of light and maximum light scattering.

Use of the preferred balloon catheter provides for displacement of the light-opaque blood between the 65 external balloon surface and the atherosclerosis plaque by inflation of the balloon. Use of the preferred catheter also allows for intermittent and cyclical illumination

2

and inflation/ deflation of the balloon so as to minimize interruption of blood flow to the vital organs and to avoid potential problems attendent to heating of the balloon material and the blood of the mammal undergoing treatment.

Activation of hematoporphyrin within atheromatous plaques may also be achieved by injecting a form of liquid light into the vascular tree. Examples of lightemitting liquids are the bioluminescent system of firefly lucerin/lucerase and the chemiluminescent system of the Cyalume Lightstick manufactured by the American Cyanamid Company. Although the organic liquidbased Cyalume Lightstick is incompatible with blood, an aqueous liquid-based chemiluminescent system has recently been developed. See "Aqueous Peroxyoxalate Chemiluminescence, Final Report to the Office of Naval Research, Contact N00014-77-C-0634" by A. G. Mohan et al. at the American Cyanamid Company, Bound Brook, N.J., January, 1982. Although the light intensity of any liquid light is less than that which is achievable with the fiberoptic delivery of a laser, activation of hematoporphyrin is a function of the product of light intensity times the duration of illumination, so that a relatively low level of light intensity for a long duration is sufficient to activate hematoporphyrin. A potential advantage of the use of liquid light is that all diseased vessels can be perfused with the liquid light, once intravascular injection of the liquid light and mixing with blood have been completed. Knowledge of the exact location of atheromatous plaques would be unnecessary, since all plaques would be exposed to the light. Should blood prove to be too light-opaque to allow a sufficient quantity of light to reach a plaque, blood replacement with more translucent liquids, such as perfluorocarbon emulsion-containing blood substitutes, may be performed prior to injecting the liquid light. For an example, in animals, of total blood exchange with perfluorocarbon chemicals, see Gollan et al, Am J. Physiol 229:1045 (1975). Fluosol-DA, a commercially available perfluorocarbon-containing blood substitute from Alpha Therapeutics, a subsidiary of the Green Cross Corporation, is currently undergoing clinical trials and has been used for massive transfusions in patients with a remarkable lack of side effects.

Since both the firefly luciferin/lucerifase system and the aqueous peroxyoxylate system can be too toxic in the doses that are required to activate hematoporphyrin within atheromatous plaques, the toxicity of these systems can be reduced markedly by modifications such as microencapsulation of some or all of the reactants in these liquids.

Accordingly, it is an object of the present invention to provide a method for treatment of atherosclerosis by destruction of the atheromatous plaque.

It is a further object of the present invention to provide a catheter for transmission of activating light directly into atheromatous plaque by displacement of light-opaque blood between the light-emitting portion of the catheter and the atheromatous plaque.

It is yet a further object of the present invention to illuminate atheromatous plaques, containing absorbed hematoporphyrin, with minimal interruption of the flow of blood to the vital organs.

Yet another objective is to illuminate atheromatous plaques with minimal elevation of the temperature of the mammal's blood.