CA2146857A1 - Intravascular catheter with infusion array - Google Patents

Abstract

An intravascular catheter provides means for infusing an agent into a treatment site in a body lumen and means for de-ploying the infusing means adjacent the treatment site which operate independently of one another. In a preferred embodiment a flexible catheter body (20) has an expansion member (28) attached to its distal end in communication with an inflation passage (54), and an infusion array (30) disposed about the expansion member in communication with one or more delivery passages (36).
The infusion array includes a plurality of delivery conduits (32) having laterally oriented orifices (34). The delivery conduits (32) may be extended radially from the catheter body (20) to contact a treatment site by expanding the expansion member (28) with an inflation fluid. An agent may be introduced into the delivery passages (36) and infused into the treatement site through orifices (34) in the delivery conduits (32). The expansion member (28) may be expanded for dilation of the lumen before, during, or after infusion.

Description

W O 94/09845 2 1 ~ 6 8 5 7 PC~r/US93/09454 INTRAVASCULAR CA 1 H~ 1 ~K WITH INFUSION ARRAY

CROSS-RE~RENCE TO RELATED APPLICATIONS
This is a con~inll~tion-in-part of appli~tion Serial No. 07/969,595, filed November 2, 1992, the complete ~licclosllre of which is inco-~ul~ted herein by reference.

BACKGROIJND OF THE INVENTION
This invention relates genPr~lly to drug-delivery devices, and more specific~lly to intravascular catheters ~or delivery of therapeutic agents from within a lumen of a blood vessel or other body organ.
In percutaneous tr~nclnmin~l angioplasty procedures, a catheter having an S e~p~nA~hle distal end, usually in the form of a balloon, is positioned in a lumen of a blood vessel with the distal end disposed within a stenotic atherosclerotic region of the vessel. The exp~nA~hle end is then exp~nAPA to dilatate the vessel and restore adequate blood flow through the region of stpnosic.
Whereas angioplasty has gained wide acceptance, it co..l;....es to be 10 pl~gued by two major problems, abrupt closure and restPno~cis. Abrupt closure refers he acute ccrl-lcion of a vessel imm~Ai~tPly after or within the initial hours following the dilatation procedure. This type of complir~tion, occ~lrring in ayp.u~ tely one in twenty cases, frequently results in myoca.~lial infarction and death if blood flow is not quickly ~ ored. The ~ dly meçll~nicmc of abrupt closures are arterial Aicsection15 and/or thrombosis. It is pOSh~i~p~ that the ability to deliver agent (e.g. ana ~ -o--,botic drug) directly into the arterial wall at the ti ne of angioplasty would reduce the in~iA~Pnce of thrombotic acute closure.
~ steno~sic refers to the re-ll~.uwillg of an artery after an initially successfi-l angioplasty. Restenosis usually occurs within the initial six monthc after 20 angioplasty. It is pos~ tPd that the delivery of certain agents directly into the arterial wall would interrupt the ce~ r events I~Aing to restpnosic.

WO 94/09845 Pcr/uss3/o9454 21468~7 2 ~
The potentiai utility of local intr~mllral drug delivery is not ~imited to atherosclerotic coronary artery disease. Other sites of atherosclerosis (e.g. renal, iliac, femoral, distal leg and carotid arteries as well as saphenous vein grafts, synthetic grafts and arteriovenous shunts used for hemo~i~lysis) would also be approl)liaLe for local S ;~ dl drug delivery. Local illLI~ulluldl therapy may also prove effir~rious in non-arterial structures, inrhl~ing the prostate via the prostatic urethra (benign prostatic l~y~;lLIv~hy~ pro~ ;l;c and adenocarcinoma), fallopian tubes via its lumen (strictures), and brain parenchyma (p~rkinson~s Disease).
At present, intravenous mP~ ti~ c are delivered ~y~lf .~iç~lly by vein or 10 regionally (e.g. intracoronary inf(-cit n). Systemic delivery is generally not well suited to the L-~ P---t of disease entities with a single site or several discrete sites of illL~
(e.g., corol~a-~ artery disease) in that it npcec~it~tps: tl) exposing sites other than the site of interest to mPdic~tion where it may have an adverse effect; (2) inf~lcing sllfficient qu~nti*Ps of agent to achieve the conrenttation throughout the entire volume 15 of distribution; and (3) exposing the agent to depr~*on and çlimin~tion by one or more organ systems remote from the site of in~lf~L. Fu.Lll~,l.llore, the tissue con- ent~tion that can be achieved at the site of in~l~ sl is often li nited by the effects of the agent at distant sites. Local illll~LlllUldl delivery obviates these problems.
Therefore, it is of particular l.ll~ol~ce to deliver the the.~ e~l;c agent directly to the 20 ~ t site by cont~ct with or ~nçt~l;on into the tissue, rather than simply relP~cing the agent into the blood ~tre~n in the vicinity of the tre~tmPnt site.
While various c~ have been developed for delivery of agents to a L~ l site within a vessel or organ lumen, such devices have ~llr~l~d from certain drawbacks. Ln particular, known agent delivery c~th~t~rs gçne!~lly do not permit25 delivery of an agent directly to a t,e~ t site indepen~çr.tly of the deploy.,.ent of the delivery ~ çh~ rent the lumen wall. For eY~mplP, known agent delivery r~thPters frequently employ an exr~n~l~hle member such as a balloon which is eYp~nded near the L~ t.-.~ -t site and brought into contact with the lumen wall. A
Ihel~ c agent is usually delivered ~hrough pores on the surface of the balloon. In 30 such devices, the pressllri7~d fluid which expands the balloon is also the vehicle for the agent. Therefore, the balloon cannot be eYr~ndPd without expell~ng the drug/vehicle n~ixture. This sch~me is in~.fficien~, in that agent is expelled before the ~ hely of Wo 94/09845 2 1 ~ 6 8 5 7 PCr/US93/09454 .. .. .
the balloon is adjacent to the lumen wall. This scheme also prevents delivery of agent without at least partly exp~n~ing the balloon. The deployment rnech~nicm (i.e. balloon exp~ncion) and the drug delivery m~ch~ni~m are inextri~hly linked.
Thus, where it would be desirable to ~ t~t~ a region of stenQcic in an 5 artery without ~im~llt~neously infusing an agent, known drug delivery c~tl-~t~l~ are of little use. Moreover, where it would be d~cir~hlP- to infuse an agent within a body lumen without deploying the balloon, known drug delivery c~th~t~rs are .cimil~rly in~ffective. FurthPrmc-re, in devices which employ the agent/vehicle u~u~Lul~ topresC.-ri7~ and eYr~n~ the balloon, the reversal of fluid flow ~ u~d to retract the 10 balloon tends to draw blood into the device, preventing fiurther use of the device until the blood has been e-xpelle~. Typically, this prevents mlllti~le l~ -t~ without withdrawing the r~th~rer for purging or repl~ce.~
A further drawback of known drug deliverv devices stems from their inc~r~rity for selective delivery of agent to various sectors of an organ lumen. Such 15 direction~ c~l llf.~l may be adv~nt~geolls, where, for eY~mpl~, only a particular portion of a vessel wall is ~iic~ced and infiJci~n to non--lice~cP~i regions is Imc~esir~hle.
Further, in certain procedures, the ability to selectively infuse different agents in dirrer~,lL areas of the lumen may be adv~nt~geous. In known devices, it is not possible to deliver agent selectively into a particular sector of the artery, or to deliver two or 20 more dirrere,.L agents into dirrt;lent sectors cim~-lt~neollcly Moreover, known drug delivery c~ti.e~l~ which infuse an agent through a porous balloon genpr~lly release the agent at relatively low l,,es~u~_s so as to merely bathe or coat the vessel wall where it is cont~rt~1 by the infi-cion ..~e..~l.cr. With such devices, the agent will g~n~lly not ~ te the lumen wall and may not provide 25 effective t~eld~y. Tlr-~ would be more effective if the ~ eu~;c agent were odelivered at yies~ules s~-ffit ient to achieve ~ l;on to the adventitial layer of the organ wall.
A drug delivery c~tl.e~r is therefore desired which can be used to ~lmini~tpr ll.elAl-e~ll;c agents to a tre~tm~nt site within a lumen of a body organ by 30 direct contact with the lumen wall tissue. Most desirably, the drug delivery c~thPtPr will be deployable ~g~in~t the ~ r~l site indepçndently of the delivery of the agent to the site. The c~thPtPr should also allow ~ t~tion of a vessel with or without WO 94/09845 ~ PCr/US9~7/094~4 21L~6857 4 delivery of a drug or other tnerapeu~c agent. Preferably, the r~thPtPr should becapable of iniecting an agent at pressures sufficient to penetrate the adventitial layer of an artery. In addition, the catheter should allow selective inf~lcior~ of an agent in various radial directions, and cin~.lllt~nPous infusion of two or more dir~rL,nt agents in 5 di~rel~L radial directions. The c~thPtPr should further be useful for tre~ttnPnt of blood vessels as well as a variety of other body organs.

Dcscl;~l~on of the Background Art Balloon-tipped catheters a~l.ro~l;dte for angioplasty tre~tmPnt procedures are described in, for example, U.S. Patent No. 5,041,089, U.S. Patent No. 4,323,071, U.S. Patent No. 4,292,974, U.S. Patent No. 4,762,129, and U.S. Patent No.
4,775,371. A catheter for locally applying mPr~ic~tinn to the wall of a blood vessel or other lumen is described in U.S. Patent No. 5,087,244, the catheter having a balloon near its distal end which is exp~n~ed with a mP~ic~tion, which then flows through minute holes in the balloon surface at a low flow rate. U.S. Patent No. 4,994,033 15 desrrihes an intravascular drug delivery c~thPt~Pr having a pair of e~ icn ...F...h~,~
concçntric~lly ~rr~nge~l near its distal end whe.~in an agent is delivered to the outer exp~ncion member, after which the inner exp~ncion member is eYp~n~Pd, thereby exp~ntling the outer member against the vessel wall and forcing the agent through minute holes in the outer member to bathe the vessel wall. U.S. Patent No. 5,021,044 2û describes an intravascular drug delivery catheter having a plurality of holes on the outer surface of the ~Ihetel body through which an agent may be delivered to a site within a vessel. U.S. Patent No. 5,112,305 describes a c~thPte~ for delivery of Illeld~eu~c agents to an interior wall of a vessel, the c~th~tpr having a balloon near itc distal end with tubular ex~pncions capable of pro~cting from its outer surface. An agent is25 delivered to the balloon which both exp~n-lc the balloon and flows through the tubular extçncior-c into the vessel wall. Other drug delivery devices are described in U.S.
Patent No. 4,693,243, U.S. Patent No. 4,406,656, U.S. Patent No. 5,015,232, U.S.Patent No. 5,087,247, and U.S. Patent No. 4,850,969.

WO 94/09845 ~ 21 ~:6 8 ,S 7 PCr/US93/09454 SUMMARY OF T~E INVENTION
The present invention provides an intravascular catheter for ~imini~tering a therapeutic agent to a L~e~ PI~ site in the wall of a vessel. The catheter will have particular usefulness in treating arterial stenoses in conjunction with angioplasty, but S will have further appli~tion in treating ~lice~ce~C affecting other body organs, such as the ~rosLaLe, biliary ducts and genital-uretal system. The c~thetPr of the ~lese.,t invention is particularly advantageous over known devices because it ~e~
deploy,l.en~ of the delivery mrch~nicm adjacent to the L~at,nent site inr~epen~çntly of the delivery of the agent to the L~ el~ site. The invention thereby f~cilit~tes 10 ~ t~tion to be l e.rolll,ed with or without infilciQ~ of an agent, as well as infusion of an agent before, during, after, or without rlil~t~tion. The catheter of the ~l, sent invention further l~el"liLs directional infiusion of one or more agents within a body lumen. Moreover, the c~thPtPr improves the effectiveness of drug tre~tment by infilcing the agent at pressures s.-fficiPnt to achieve penetration into the adventi~ial layer 15 of the organ.
In a specific embo~imP~t, an ~)~dtUS for infiusing an agent to a tre~tment site in a body lumen comrric~s a c~thPtPr body having a distal end, a ~ro~ lal end and first and second p~cc~pes th~,rcbeLween; a guidewire ÇxtPn~ling from the distal end of the c~thPtçr body; an e~r~ncion member ~tt~t~hP~l to the c ~I.çl~r body 20 near the distal end, the interior of the e~cp~ncion member being in fluid col.~ *on with the first passage; and an infilcion a~Tay in commllniç~tion with the second p~c.c~ge and disposed adjacent a lateral surface of the ex~ ;on mPmber so as to be deployable Pnt to the tre~tment site by deploylllenl of the e,c~ ;on ...e~..her, wherein the infusion array is operable for infilcing an agent to the L~ ..F ~t site in-iepçntlçntly Of 25 deployment of the e,~ ;on .~~---h~r.
In a preferred embodim~nt~ the infilcion a~ay comprises at least a first tubular delivery conduit having a plurality of orifices on a surface thereof and an axial p~Cs~ge which is in col~ ullication with the second p~c~e in the c~tlletPr body.Usually, the infusion array will inrhlde a plurality of tubular delivery conduits disposed 30 at various positions about the periphery of the balloon. The orifices in the delivery cor~ C will typically be radially-oriented so as to open directly onto the tre~tmP-nt site when the conduits are positionPd adjacent to the vessel wall.

W0 94/09845 ,~ Pcr/uss3/o9454 2i4~7 6 ~
The delivery conduits may be connectPd to a single delivery passage in the c~th~t~r, but in a plcre~l~d embo~im~nt~ the c~th~tPr body will include a plurality of delivery p~C~ges~ each p~cs~ge being in co~ iÇ~tio~ with one delivery conduit.
An agent may be infilced through sel~c~d delivery conduits by delivering the agent S through the collc;s~onding delivery p~c~e or p~C~gec. In this way, infilci~n may be pelr~ ,ed at selec~d directions, and two or more agents may be infilsed through s~lPcted delivery conduits .cim~llt~nPQucly.
The e~ ..s-on ...F ..I~ei may comrrice a balloon similar to those of conventional balloon ~ t~tit~n c~th~t~rs. In a preferred embo~lim~nt, the exl.~ ;on 10 member and delivery cond~litc will be integrated into a single, monolithic extrusion, the conduits comprising p~cc~ges in or along the wall of the e~p~ n memher.
Alternatively, the delivery conduits may be structurally separate from the balloon and disposed on its exterior surface.
The e~p~ncion member may ~lt~rn~tively comprise a balloon fixed to an 15 entirely separate ~ t~tion c~thPter removably disposed in an axial p~c~e through the c~ll.r~r-l body. In this embo~im~nt, the delivery conduitc will usually be mounted to an eYp~nr3~1-1e support member disposed about an opening in the catheter body in which the balloon of the removable rlil~t~tion c~thP-ter resides.
The e~cr~ncion mPmber will be e7cr~ndPd using an eXl~n~;on fluid 20 supplied through the first p~c~e in the c~thet~r body. Rec~-lse the e~ ion ~l~ell~bcr is fluidly i~ol~ted from the delivery conduils, ~ihe ek~ s;on fluid will not irtcl--de the infilcion agent, which is infilsed sepaldLely via the device.
Deploy,l,ent of the e~ n member brings its lateral wall along with the delivery cQn~llitC of the infilcion array ~di~rPrlt to the ~ t site. The25 exp~ncic~ ne"lbcr is used only for deploying the infilcion array adjacent the vessel wall and/or t~ t~ltillg the vessel, and plays no part in infilcing an agent through the infusion array. The infilcion con~illitc retain their fluid-con~llc*ng capacity whether positionPd against the trp~tment site or retract_d toward the center c~thP~r body.
Thus, an agent may be infused through the infi(l~ion array irrespective of whe~er the 30 exp~ncion member is exp~nded or retracted.
The infusion array will be configured to infuse an agent at s~ffiriPnt plt;S~ to ~ n~LIate to a depth of at least the media, and preferably into the adventitia 2~ ~68S7 Pcr/US93/09454 of the anerial wall. In a preferred embo-1imP~t, the delivery conduits of the infusion array will be composed of polyester, with an inner diameter on the order of 0.1-0.2mm, a wall thi~kness on the order of 0.05-O.lmm, and orifices of 10-50 ,um inAi~mPtpr. The use of a plurality of delivery con~llitc of relatively high stiffnPss and S small cross-section, each supplied through indepen~lçnt delivery p~C~es from the )J.`OAilllal er.d of the device, rather than a single delivery p~c~ge with a manifold at the distal end, provides a stiffer hydraulic system. This allows for the infusion of more precisely-ll,e~elGd doses than is possible in known devices and results in a s~lhst~nti~lly more effi~ient metho~l of agent delivery.
In a preferred aspect of the method of the presellt invention, an agent delivery catheter is position~Pd in a blood vessel with an infi-~ion array at the distal end of the c~thPt~r near the tre~tment site. An e~p~ncinn member at the distal snd of the c~thPter, which is fluidly isolated from the infilcio~ array, is deployed so as to position the infusion array adjacent a L~G~t~..e.~l site in the vessel lumen. Thereafter, an agent is 15 delivered to the infusion array through at least one delivery p~cs~gP~ in the c~he~
The agent is then inftlced into the trc~tmPnt site through a plurality of orifi~ es in the inftlcinn array.
In a particular emborlim~nt~ the agent is delivered from the ylo~ al end of the c~th~o~r through a plurality of se~.t~ delivery p~cs~ges to a p~ y of 20 delivery contlnitc at the distal end of the device, the orifices of the infilcion array being arranged on the outerrnost snrf~ees of the delivery conduits. In t~us way, delivery of the agent to each delivery conduit may be controlled inAepen~ently. Thus, an agent may be infilsp~d through a first delivery corA~Iit without infilcing the agent through a second delivery CQ-~dll;l, or a first agent may be infilceA through a first delivery co~.d~
25 while a second agent is infilspd through a second delivery cond~lit Ln a speçifi~ embo~;...el-t, the rnethnd will be used for ~ of COlOn~ artery disease, whel~in the c~th~tPr is posi*o~Pd with the inftlcion array near a stenotic or otherwise Aicp~ced site in an artery. Usuall~, a fL~ced guidewire mollnt~PA
at the dis~al end of the c~hPtPr, or a movable guidewire e~ g through a guidewire 30 pas age in the catheter, will be used to guide the c~thPtPr into the vessel. The eYp~ncinn m~-rnher may be deployed to dil~t~t~p the artery for l~s~o.~;orl of ~e~ tP
blood flow, with or without infilcion of an agent through the inf~lciorl array. Before, WO 94/09845 . 2 1 46857 Pcr/us9~/09454 during, after, or without ~ t~tion, one or more agents may be inft-ced through the infi-cinn array into the lle ~ pt~t site.
In alL~,..aLi~e emboflimPntc, the metnod of the invention may be used for tre~tmPnt of various other body organs, inrlutling the biliary ducts, or the genital-uretal S organs.
A further underst~n~ling of the nature and adv~nt~ges of the invention may be rea~ized by reference to tne re~ g portions of the sperific~tion and the drawings.

BR~F DESCRIPIION OF TEIE DRAVVINGS
Fig. 1 is a perspective view of an agent delivery catneter constructed in accordance with the princi~hPs of the ~1eSe;nL invention.
Fig. lA is a transverse cross-section of a distal portion of the c~ll.PtPI of Fig. 1.
Fig. lB is a transverse cross-section of the c~thPter shaft of the c~theter of Fig. 1.
Fig. lC is a side cross-section of the pLuAi~ end of the c~h~t . of Fig.
1.
Fig. lD is a transverse cross-section through the ~o~ al end of the C~ l of Fig. lC.
rig. lE is a longitl-l1in~l cross-section of the distal end of the c~thPter of Fig. 1 cutting through two drug delivery conduits.
Figs. 2A-2C are transverse cross-sections of a portion of the ~ ;on member and delivery cor~ its of the c~thPteI of Fig. 1., showing various ~ t;~reembo~l;..,,..~ thereof.
Fig. 3A is a perspective view of a further ernbo~imP!nt of an agent delivery c~the~,r constructed in accordance with the principles of the ~1eSellL inven~on.
Fig. 3B is a transverse cross-section of a l)~o~.l,lal end of the c~thPt~r of Fig. 3A.
Fig. 3C is a transverse cross-section of the c~thP~ter shaft of the c~thP~r of Fig. 3A.

WO 94/09845 r . j~" ~ PCI'/US93/09454 Figs. 4A and 4B are perspective views of a further embodim~nt of an agent delivery catheter constructed in accordance with the prin~iplPs of the ~lcscn invention, showing the e~cp~ncion member in the nnc~ nqed and e~p~nrie~
configl-r~tions, respectively.
Fig. 4C is a transverse cross-section of a distal portion of the c~l.Pl~r of Fig. 4B.
Fig. 4D is a transverse cross-section of the c~thPter shaft of the c~th~t~.
of Fig. 4B.
Fig. 4E is a longitnrlin~l cross-section of the distal end of the c~thPt~r of Fig. 4B.
Fig. 5 is a perspective view of a further embo~imPnt of an agent delivery catheter constructed in accordance with the principles of the ~l~senl invention.Fig. 6 is a perspective view of still another emborlimPnt of a drug delivery c~thPter construct~d in accoldance with the principles of the ~l~,senL invention.
Fig. 7 is a side view of a distal end of a further embo-iimPnt of a c~ . t constructed in accordance with the prin~iplPs of the ~ senl invention.
Figs. 7A-7B are transverse cross-sectionc of the c~theter of Fig. 7 through the c~thPter shaft and through the e~r~ncion Ille-l~ber, respectively.
Fig. 8A and 8B are side views of the c~thPter of Fig. 1 po,citiorpd within a body lumen accold,ng to the principl~ps of the mPthoc~ of the ~r,se.l~ invention.
Fig. 9 is a perspective view of a further embodimPnt of an agent delivery c~thP~çr constructed in acco~lallce with the principles of the invention.
Figs. lOA and lOB are side elevational views of a distal portion of the c~h~t~r of Fig. 9 in un~eployed and deployed configl-r~t~ c~ respectively.
Fig. 11 is a transverse cross-section through line 11-11 in a ~lo~ullal portion of the shaft of the c~l.elel of Fig. 9.
Figs. 12A-12E are transverse cross-sectionC through line 12-12 at the dis~al end of the shaft in the catheter of Fig. 9 illustrating various embo~limentc of the ~;rfG.~ g ele...ell~c in the infi-ciorl array.
Fig. 12F is a top elevational view of a further embo~1imPnt of the i~;r~4.-;..g elemPnt in the c~thpter of Fig. 9.

W O 94/09845 ~2 1 4 6 8 S 7 PC~r/US93/09454 Fig. 13 is a side cross-section of a further embodiment of the infusion array of the catheter of Fig. 9 wherein the delivery conduits are secured to theperiphery of an el~ctomeric sleeve.
Fig. 14A is a transverse cross-section of the infilcion array of Fig. 13.
S Fig. 14B is a transverse cross-section through the infusion array Whefeill the elastomeric sleeve is disposed exsern~l to the delivery con~--itc.
Figs. lSA-lSB are a side cross-section and a ~~ ,ec~/e view, respectively, of the distal tip of the c~thPter of Fig. 9.
Fig. 15C is a side cross-sectional view of a further emboriimPnt of a distal tip constructed in accordance with the principles of ~e invention.
Fig. 16 is a side cross-section of the manifold assembly at the l)ro~ al end of the c~thPter of Fig. 9.
Figs. 17A-17D are side views illustrating the C~ r of Fig. 9 positir)n~
in a body lumen acco~ling to the method of the invention.
lS Figs. 18A-18C are side cross-sec*nn~l views of a distal portion of the infusion c~thP~r of Fig. 9 illustr~ting the radiopaque markers on the :,I;rL..;.Ig elP l.,p,,,lc.

DESCRIPIION OF SPECI~IC EMBODlMENTS
Referring to Fig. 1, the intravascular drug delivery c~lhe~r of the ~l~ sWlt 20 invention int~ ies an elong~t~ flexible shaft 20 having a distal end 2~ and a l,lo~
end 24. A movable guide wire 26 çyt~nrls through the c~th~tPr and beyond its distal end 22. An eXp~ncion member 28 is ~tt~h~ci to the c~th~t~r shaft 20 near distal end 22. An irlfilci~m array 30 comrricing delivery con-lllitc 32 and orifices 34 is disposed about the exterior sllrf~re of e~ ;on m~.ml~er 28. Cond-~itc 32 are in cu...~ tion with delivery p~c~Ees 36 in c~sh~ter shaft 20. A h~lcing 38 is mollnt~l to ~ro~
end 24 of catheter shaft 20. ~o~cing 38 in~ es an agent introduction port 40 and an infl~tion fluid intro~uction port 42.
A distal portion of the c~theter will now be described with reference to Figs. lA and lE. A guidewire p~CC~ge 44 is disposed cen~rally in shaft core 46, through wnich guidewire 26 is slidably disposed. F.xp~nci~ll member 28 s-l~.ounds shaft core 46, with delivery co~ itc 32 disposed about its ~)c.;~hc.y Delivery WO 94/09845 ~ 68~ 7 Pcr/us93/09454 il conri~litc 32 incl~lde an axial pAC~ge 50 in commllnirA*on with orifires 34. Distal ends 33 of delivery cond~litc 32 are sealed. In a preferred embo~liment delivery collrh-itc 32 and ex~Ancion member 28 comprise a single integ~AtP~, monolithic extrusion, with the delivery conduitc forming lnngitllrlin~l pAcc~ges in the wall of the e~A..~;on ,..~...1~. ,.
S It will be understood that the cAth~ t~r of the p~senl inven*on may have any of a varie~y of guidewire co~fig~ *r)rls. For example, as shown in Figs. 7, 7A
and 7B, rather than being licrose(l cçntr-lly in the shaft core, guidewire pAcsAg~ 244 may be offset from the center axis in-lç~e.~c..l of and PA~1lP1 to inflAtirn lumen 54.
Moreover, such a guidewire pAcsAge need not extend through the entire length of shaft 20, but may instead have a lateral opening 245 at a point aiong shaft 20 through which guidewire 26 exits the offset guidewire p~Cs~ge 244 and shaft 20, such that guidewire 26 and shaft 20 are indepenr~ent of each other at the plo~ al end of the device. Such an offset guidewire is riescrihed in U.S. Patent No. 4,748,982, the comrlrtP r~icrlocllre of which is incol~uldlcd herein by lefere.lce. I~LI1lhP ~ ...ore, a fixed guidewire (not 15 shown) extPnrling from distal end æ may be used in lieu of movable guidewire 26.
As illnstr~trd in Figs. 2A-2C, delivery con~ itc 32 may be integr~tPA
with e~l~A~ ;on memher 28 at various pocitinns relative to e-Ytçnor surface 48. In the embo~iimPnt of Fig. 2A, delivery cQn~]~ C 32 are disposed e~tP ior to surface 48 so as to protrude lhcfcr,u-ll. In the embo~ .t of Fig. 2B, delivery con~ it.c 32 are 20 disposed plill~ily in the interior of e~l~A~tC;on ~llel.lbcr 28 with orifices 34 eY~ nrl;.,g through the ~hirl~ness of the çxrAncion member, such that surface 48 has a :~ib:~lAIll;Ally smooth contour about the lJ~ el ~ of the e~ ;nn .-- ..bef. Fig. 2C shows Anothçrembo.1imPnt whel~in delivery conduits 32 are dicpos~pd centr~lly in the wall of exrAncion ...e-..l,cr 28, producing only a slight ~ro~ e~,ce on surface 48.
The ~ her of delivery con~ it-c 32 may vary from one to eight or more, but in a ~r~ d emborlimP-nt, there will be four delivery con~--itC spaced at a~rox;...~t~ly 9o degrees about the circumference of e~ nC;or member 28. Delivery con~-itc 32 may be disposed in various ~ nge.... -l~ about the ~ he.y of ex~A~;on memher 28, both sy.~.~..Pl~ ;CA11Y and a~y...~ Ally. For example, the delivery 30 con~itC may be arranged such that a majority or all of the con~--its are on one side of the ex~A.~cion member. Or, the delivery col-du;~ may be A~nged with two pairs ofclosely-spaced conrlnitc on opposing sides of eXpAQcion member 28. Moreover, the W094/09845 ~ 6~57 12 Pcr/uss3io94s4 delivery co~A-.itc may be of different Ai~mPters, and may have varying sizes, shapes and ~rr~nge~ of orifices 34. Orifices 34 may be in a single row, but may also bein a non-linear arrangement, or in multiple rows or groups on each delivery conduit.
Delivery conduits 32 will preferably have sufficient rigidity in the S transverse direction so as to remain l-ncoll~rs~P~ when pocition-P,d by exr~ncion member 28 against a wall of artery.
Delivery con~l--itc 32 and orifi~^~es 34 will preferably be co~fig1~red to infuse an agent at s--fficiP-nt plGS~ul~ to pC-~Ul~t'~- into the adventitial layer of the organ wall. Usually, the device will achieve ~ PI. .I;on to at least the media. P~s~ures of at least 4 ~tmos~llfrG5 are generally necec~y to achieve such yel-PL~ation. The preSGIlt invention, in an exemplary emboAimPrt, will infuse the agent at a ~leS~ , of up to l0 atrnos~heres or more. This will be acsomplished by delivering the agent under pressure from the ~roxilllal end of the catheter through delivery p~C~ges 36. Inaddition, the geometry and m~teri~l of the delivery conA~litc 32 will be s~lecteA to f~rilit~tç ~cnP~ e infusion. In a ~lefeiled embo(limpnt~ the delivery cond,li~ 32 will be co--,~osed of polyester, with an intprior ~ tel of about 0.1-0.2 mrn, and a wall thirlrnPsc of about 0.05-0.l0 mm. Orifices 34 will have a Ai~ f te~ in the range of 10 to 50 ,um.
Referring now to Fig. lB, c~thPter shaft 20 ~lo"i,.,al to exp~ncior~
n,e."ber 28 inçlllAe5 shaft core 46 with guidewire 26 extenAing through guidewire p~ P. 44. An outer body 52 of ~ne c~li,rler shaft ~ lo~mds an infl~*~ln p~c~ge 54.
Delivery p~Cs~es 36 and outer body 52, in a l,ler~ ,d embo~ t, comprise a monolithic extrusion, with a variety of possible config~ tionc. In the embodiment of Fig. lB, the delivery conAnitc 36 are disposed on the eYt~rior surface 56 of outer body 52. Other possible config~ tiQnc will be similar to those ilTI~st~teA in Figs. 2B and 2C and described above in connec~2on with delivery conduits 32. Further embo l;", --lc are shown in Figs. 4A-4E and Fig. 5, descrihed more fully below.
F~tp~ncinn mPmher 28 may be adhesively ~tt~rhed to c~thete- shaft 20, but will preferably be formed as a single extrusion, along with delivery p~cs~ges 36 and delivery conduits 32, forming a contin~lollc~ monQIithic structure from p~oxi~
end 24 to distal end 22. While known c~thrter f~hrir~h~n tecl~ ues have been used to forrn a baUoon at the distal end of a tubular shaft, it is her~ toÇo.~ unknown to form a WO 94/09845 13 ~ ~ ~ 68S 7 PCr/US93/09454 balloon at the distal end of a monolithic extruded structure with delivery conduits wit'nin tne wall of the balloon and delivery p~Cc~gec within the wall of the shaft ir.
col...--.-.-it~*on with the delivery conr~nitc Referring now to Figs. lC and lD, housing 38 in~ln~es an ~nmll~r S rnanifold 58 in co.. ;~*on with a p~Cc~ge 60 t'nrough agent intro-l.. c*on port 40.
Distribution p~c~gPs 62 e~tend distally from manifold 58 to c~thPter body 20, where they connect to delivery p~Cs~ges 36. Infla*on p~e~ge 54 extPn~C through hollcing 38 and connectc to p~c~ge 64 in infl~*nn port 42. Shaft core 46 is disposed within inflation p~Cc~ge 54, with guidewire 26 e~t~n~ing through guidewire p~Cs~ge 44.
A further embodiment of the c~thP,ter of the ~r~se.ll invention is illustrated in Figs. 3A-3C. In this embo~iment housing 38 at the ylo~ulllal end of the device has a plurality of agent introduction ports 140, each introduction port being in comm--ni~tion witn one of deliver,v p~c~ges 36 in c~thetPr shaft 20 via connPction passages 162. In other respects, the c~thPtPr is much like that described above in 15 cormection with Figs. lA-lE, except that delivery p~Cc~ges 36 and delivery con~ itc 32 (not visible) have the configuration illllstr~tpd in Figs. 2B and 3~, respectively.
By providing Se~ d~e intro~ction ports 140 for each delivery p~Cc~ge 36 and delivery conduit 32, the invention as embodied in Figs. 3A-3C ~ell,.i~ direction~l infusion of one or more agents through orifices 34 in different delivery conduits 32 of 20 infilsion array 30. This may be advantageous where only a particular portion of a vessel is to be treated, and in~l~ion to other portions is l~nr~ir~hle. Direction~l infusion may further be useful to infuse a first agent through one or more delivery conduits 32 at sel~c~d directions, while ciml~lt~nPously infi~cing one or more other IhP~ agents through other delivery COn1~I;I`; In this way, for example, a growth-25 inhibiting agent may be delivered to a stenodc region of the vessel through the delivery Oco~ on one side of the c~thet~r, while an anti-co~glll~nt is delivered through the delivery conduits on another side of the c~thPter.
A further embo~imPnt of the c~thPtPr of the ~Sell~ invention, illllst~tpll in Figs. 4A-4E, comprises a se~dte ~ t~tion c~thPt~r 70 of conventinn~l construction 30 removably disposed in an axial passage 72 in catheter body 20. An exp~nd~ble support member 74 is ~tt~çhP,I to the distal end of c~thPtPr body 20, more clearly illllctr~tpd L'l Figs. 4C and 4E. Support member 74 compri~S a tubular structure having a plurality , 2 1 ~ 14 Pcr/uss3/o94s4 of separate support sections 75. Delivery conduits 32 are disposed on a lateral surface of support sections 75, and are in co,.~ ic~tion with delivery passages 36 in c~thPter body 20. Orifices 34 are disposed on a lateral surface of delivery conduits 32, with distal ends 33 of delivery conduits 32 sealed. While support member 74 and delivery 5 conduits 32 are shown as separate structures mounted to c~thPter body 20, it will be understood that catheter body 20, SuyyOl~ member 74 and delivery co.,duils 32 may comprise a single (monolithic) extrusion, as described above in connection with Figs.
lA-lE.
Removable rlil~t~tion catheter 70 is slidably disposed in axial passage 72 10 in c~thPtPr body 20. The f~ t~tion c~thPter 70 will be of conventional construction, and inrllldes a guidewire passage 76 in a core 80 as shown in Fig. 4D, through which guidewire 26 is slidably inserted. An outer casing 82 surrounds core 80, defining an inflation passage 78. An expansion member 84 is formed from, or adhesively mounted to the distal end of casing 82, and is sealed at distal end 22 about core 80. When ~ t~tion catheter 70 is positionp~ in c~thPtPr body 20, exr~n~iQn member 84 resides within interior lumen 86 of support mPmber 74. Guidewire 26 and/or core member 80 extend distally hrough a distal opening 88 in Suy~ulL mpmber 74.
Support member 74 will be constructed of a ll,atelial similar to that of exr~n~inn l~,ember 84 so as to expand Lher~wiLh. When e~ ion member 84 is 20 infl~tPd, as shown in Figs. 4B and 4C, support section~ 75 are distended and se~ d as uhey expand oulw~u~d with the e~ n~ion member.
A further ~lt~prn~tive embo~impnt of the c~thPt~r of the yl~selll invention is ill--ctratP~ in Fig. 5. In this embo.limP-nt the c~thPtPr comprises a plurality of delivery conduits 90 e~rt~Pr1(ling from the distal end 22 over exl-~ ;on member 28 to the ~o~ lal end (not shown) of c~t~.et~r shaft 20. Delivery conduits 9G have orifices 34 on a lateral surf~ce thereof oyyOSik; e~cr~nd~hle ~I.ellll)er 28. Delivery c~n-~litC 90 be f~c~Pned at distal end 22 and to the extpric)r of e~th~PtPr shaft 20, but will be nn~tt~ Pd tû e~Yp~ncion nl~lllber 28. This ln~lllU~:i delivery conduits 90 to be ~lisp~ d as exp~n~iQn member 28 is infl~tPd, without creating stress concPntrations on the 30 surface of expansion member 28 as might be created by direct ~ chmPnt of the cûn~uil~ thereto. Fur~ermore, e~ ion member 28 may be compliant. ~'~thPt~r shaft 20 and exp~ncion member 28 will otherwise be subst~nti~lly si~rilar to those of W094/09845 5 ~ ?1~68~7 Pcr/us93/o94s4 Figs lA-lE or 3A-3C. Delivery co~ itc 90 may be manifolded at the ~ro~ lal end of the c~thPt~ as in the emboriim~P~t of Figs. lA-lE, or conn~ct~d to separate agent introrluction ports as in Figs. 3A-3C for direction~l infusion. The invention asembodied in Fig. S p;ovides a c~theter of very simple, low-cost COI.sL,.lction with 5 indepe~ient infusion and exl,~n~ior- as well as direction~l infi-cion c~r~biliti~os.
Figure 6 illustrates a further embo~iim~nt of the c~theter of the pl~ se.lt invention. The e~tl.e~er inclllAes a body 20 having an e~ .C;on memher 28 near its distal end 22, a guidewire lumen 44 ~ f..~ through the body 20, and a pl~lrality of delivery p~c~ges 36 integrated with body 20 in a lorlgih-riin~l di~e~oll. In this 10 embo iim~nt, a ~ro~....al infilcion array 30a is disposed on the e;~ shaft lJio~i,llal to expansion member 28, while a distal infusion array 30b is disposed on the c~ll.el~r shaft distally of exp~ncion member 28. ~nfi)cion arrays 30a, 30b incl~de a plurality of orifi~es 34 disposed on a lateral surface of delivery con~llitc 32, which are in fluid connP-ction with delivery p~Cs~ges 36. Distal portion of c~th~t~ body 20 distally of lS eYp~n.cin~ e~ er 28 may be of reduced ,i;,.. t~-~ to f~-ilit~tP po~i*nning in a vessel.
In this emboriimpnt~ the c ~t~.~ter of the ~l~sel-~ invention facilit~tPs riil~t~tion using eYp~ncion me,llber 28, while i..r-~;..g an agent through infilsion arrays 30a, 30b.
~nfi~cion may be pt:lroll.,ed inriepen~ently of riil~t~tion, pe~ ;.lg infilsiol~ of the agent before, during, after, or without riil~t~ti~m. rul~ r, as in other embo~ -f -l~, each 20 delivery p~Cc~ge 36 and delivery condllit 32 col~ -ation is in~lependent of each other, so as to f~ilit~tP direction~l inî~Cior and/or inf~l~iolt of two or more dirre~ t agents cimlllt~nPo~lcly. It is also understood that the c~thpt~r may inr~ le only one of either distal infusion array 30b or ~iu.~i."al infilc~ array 30a, and that orifi~s 34 may be in~lllded only on selçcted ones of delivery con~ tc 32. rulther, the c~ f may 25 cornpric~ in ~d~iition to infil~iorl arrays 30a and/or 30b, asl infilsion array about the periphery of the e~p~ncion mPmher in the ...~ r descrihe~ above with lefe.~ nce to Figs. 1-3.
~thPters constructed in accolda.lce with the prinrirles of the pn senl invention may optionally be modifiP(l to provide for perfusion or by-pass blood flow, as generally described in U.S. Patent Nos. 4,661,094, and 4,892,519, the disclosures of which are incol~t.,dL~d herein by reference. (~enpr~lly~ such per{i~cinn flow can be provided by one or a series of perfusion ports on tlle ~ro~ lal side of the ex~ ;on Wo 94/09845 ~ 6 8 5 7 Pcr/US9~/09454 16 ~
member 28, which ports permit the flow of blood into the shaft core 46 and eventually out through the distal opening of said core. In this way, blood flow can be m~int~in even when the e~p~n~ n member 28 is exr~ndçd and would (in the absence of the perfusion capability) block blood flow.
S It should be understood that the catneter of the l~lese,-t invention is suitable for delivery of a variety of thelayc;.lLic agents inclll~ing ph~rrn~rentir~lc~
proteins, peptides, nucleotides, carbohydrates, poly~rrh~rides, muccopoly.c~rch~ri~es, sirnple sugars, glyco~.~ oglycans and steroids. The yl~se.-t invention f~cilit~tes delivery of such agents in a variety of forml~l~tio~c, inrlll~ing aqueous vehicle or liposome. The drug delivery catheter is furtner useful for delivery of viral particles to f~cilit~tP gene transfer. The agents delivered may ~t~roill. a variety of fi-nrtio~c, inrl~lding a~ uo-l~botics antiplatelets, ~n*met~holics, growth factor inhibitors, growth promoters, ~ntiro~ulants~ ~ntimitotics~ and antibio~ics.
In a further embo-limPnt, illnctr~t~d in Figs. 9-17, the agent infusion catheter is configured to slidably receive a conventinn~ t~tion c~ll.ft l within an axial guide p~c~ge in the infusion c~thPtçr shaft. This allows the ~ t~tiQll C5~11.f ~l t to serve as a guide wire for the infilcion c~thPter to guide the r~thçtPr to the Ll- ~I.,.P-~
site, f~rilit~t~s ~ t~ti~ln of a s~notic vessel indepe~ld~ntly of agent infilcion, and ~lll~i~ the use of any of a variety of commercially-available r~ t~tiQn c~thPter~ in conjnnrtion with the agent infusion c~th~tPr of ~e invention. Dilatation r~thPters suitable for use with the infilcion c~thPt~r illllssr~t~d in Figs. 9-17 are clescrihe~, for eY~mrlP, in U.S. Patent No. 5,041,089, U.S. Patent No. 4,323,071, U.S. Patent No.
4,292,974, U.S. Patent No. 4,762,129 and U.S. Patent No. 4,775,371, the coi~.r'~P
dicclosl~res of which are incorporated herein by reference. Such ~ t:ltion c~itl~e~ ;~ are co~ elc;ally available from, for exarnple, Advanced Cardiovascular Systems, LnC., of Santa Clara, California.
Referring to Fig. 9, in a preferred embo~imPnt agent infusion c~thPt~Pr 200 in~ludes an elo~gate flexible shaft 202 having a distal end 204 and a ~ uual end 206. A manifold assembly 20% is fLxed to the ~lu~ llal end of the shaft and inr~ ie~
~ t~tion catheter port 210 on i~ plo~il"al end and an agent introduction port 212 in a fitting 214 provided with a Luer lock (not shown), securecl to the ~scemhly. At the distal end of the shaft 202 is an inf~lcion array 216 having a plurality of orifices 218 W O 94/09845 ~ 6 8 PC~r/US93/09454 along lateral surfaces of the shaft. Shaft 202 comprises a plurality of axially disposed agent delivery passages 220 extending from the ~loximal end which are connloc~d to a corresponding number of agent delivery conduits 222 at the distal end. Orifices 218 - are in communication with interior axial lumens 233 in delivery conduits 222. An axial S cut or slot 224 is formed in shaft 202 between each of delivery conduits 222 such that the delivery conduits are separated from one another by the slots. A stiffening element 226 is disposed in at least a single delivery conduit 222, as described more fully below.
A conically tapered distal tip 228 is fixed to the distal end 204 of the shaft.
In a preferred embodiment, shaft 202 will be constructed of materials and will have dimensions selected as al)pro~.iate for insertion of the shaft tr~n.cll~min~lly inside a guiding catheter (not shown), in a blood vessel. In an exemplary embodiment, shaft 202 will have a length in the range of 110 to 150cm, and an outer dian~eler of l.lmm-2.3mm (0.04 to 0.09 inches). Infusion array 216 will be approximately 10 to 60 mm in length. C~th~ter shaft 202 may be any of a variety of biocompatible, flexible materials inclllding, for exarnple, polyester, polyethylene or polyamide. Preferably, as described above, catheter shaft 202 (inr.l~lr~ing delivery p~ es 220) and delivery conduits 222 will comprise a single, monolithic extrusion from proximal end 206 to distal end 204.
As shown in Fig. 10A, in an undeployed configuration, infusion array 216 is ~ligne~l with and has an outer diameter generally equal to that of the proximal portion of shaft 202. As shown in Fig. 10B, a dilatation catheter 230 may be positioned through an axial guide passage of shaft 202 (described below) such that a balloon or other expansion member 232 at the distal end of the t~ t~tion ca~,e~r is within infusion array 216 ~dj~cent delivery condllit~ 2æ. By e~cp~n.ling balloon 232, infusion array 216 is deployed radially outward to bring orifices 218 ~dj~cent to a treatment site on a vessel wall.
Fig. 11 illustrates a transverse cross-section through a ~,roxin.al portion of shaft 202. A guide p~s~e 234 extends longihldin~lly through the catheter sllaft for slidably receiving a dilatation catheter. Guide p~ge 234 may be coated with a lubricious material such as a hydrogel or fluorocarbon polymer, for example, fluorinated ethylene-propylene or polytetrafluoroethylene, available co,l"~ercially under the trademark Teflon0 from DuPont. Such a coating facilitates longihltlin~l positioning WO 94/0984~ 4~8 5 7 18 PCr/US93/094~4 and ~lignment of a ~ t~fion catheter in guide p~ge 234 when catheter 200 is disposed in a tortuous configuration in a vessel. Guide passage 234 will have a di~ ter of 0.7-2.0mm (0.03-0.08 inches), preferably 1.2-1.8mm (0.05-0.07 inches), suitable for receiving most commercially-available dilatation c~th~ters in current use.
S Delivery p~ges æo run parallel to guide pa~ge 234. In an exemplary embodiment, delivery passages 220 are disposed in longih.~lin~l ribs 236 which protrude radially outward from shaft 202. Delivery passages 220 will have an interior height (or ~ meter, if round) in the range of O.Olmm to 0.7mm (~0.005-0.03 inches).
Figs. 12A-12E illustrate transverse cross-sections of the distal portion of shaft 202 through infusion array 216 in various embor~iment~. In the embodiment of Fig. 12A, delivery conduits 222 are separated from each other by slots 224 so as to permit lateral expansion for deployment of the delivery conduits. Delivery conduits 222 have an axial lumen 238 which is in comml-ni~tion with delivery passages 220 in the catheter shaft. Delivery conduits 222 surround guide passage 234. Stiffeningelements 226 are disposed within axial lumen 238 and occupy only a portion thereof to permit flow of agent through the lumen. In the embodiment of Fig. 12A, stiffenerelements 226 comprise ribbon or bar-shaped rods of generally rect~ng~ r cross-section. The rods may be unrestr~ined in the axial lumens of the delivery conduits, secured at their distal end to the distal tip as described below, or co-extruded in the walls of the delivery conduits, also described below. Stiffener elements 226 may be any of a variety of materials such as st~inl~s~ steel, t~nt~lllm, nickel-tit~nillm, or tungsten and having a geometrical configuration leading to greater axial rigidity but being latelally more flexible and resilient. The stiffetling elements may extend from distal end 204 to proxirnal end 206 of shaft 202 through the delivery p~ges, or may have a shorter length, e.g. 30-70 mm, so as to extend from a point near distal end 204 to a point just proximal to infusion array 216.
Stiffener elements 226 serve several functions. First, the stiffener elements help to m~int~in the patency of axial lumens 238 in ~e delivery conduits.
Second, ~lirr~l.e,- elements 226 provide stiffness and resilience to delivery conduits 222 such that, following expansion of the delivery conduits, ~ey will recoil back to the undeployed configuration. Third, stiffener elements 226 serve to m~int~in the relative WO 94/09845 1~ ~S7 gnment be ween the delivery conduits during longitn~in~l positioning and later exr~ncion, so that the delivery conduits remain a~lo~din~ately equally se~dld~d from each other when deployed, f~cilit~ting uniforrn tre~tment of an area of the vessel wall.
I~ul~lellllore, a stiff~on~r el~ment 226 of rect~ngnl~r cross-section allows controlling the S relative m~gnitnde of lateral versus radial stiffnPss. In the confi~l~r~tion shown, the ben-ling stiffnPcs of stiffener elpmpnt 226 is subst~nti~l1y less in the radial direction about a first axis perpenrlic~ r to the shaft than in the lateral direction about a second axis perpen~icnl~r to the shaft and ~el~en~licl~l~r to the first axis.
Fig. 12B illnctr~tes a further embo~iim~nt of delivery con~l-itc 222 and s~;rr~,-;.. g elPmPntc 2~6. In this embodimp~nt~ slot 224 is cignifi~ntly wider than in previous embo-1imPntc, such that sl~kst~nti~lly all of the m~tPri~l between delivery conduits 222 is removed. Further, in this embo~im~nt, stiffçner elementc 226 comprise rods having a round cross-section With such a shape, the stiffen~r ele...f-.-lc are particularly effective in ~ lt~ g the patency of axial lumen 238. Further, the 15 stiffener elemPntc of round cross-section will not tend to block p~Cc~ge of an agent through orifices 218 if the rods float to the outer s~rf~te of the axia~ lumen.
In the embo-limP!nt of Fig. 12C, ~I;rLnpr ÇIP..~P.lllc 226 CQ-..p. ;.ce rods round in cross-section embedded in the outer wall 240 of delivery cor-~nit 222. It should be understood that sl;rr~ er el ... ~ of various cross-sect~nn~l shapes may be 20 embedded in the wall of the delivery cond~it~ in the ..I~".~er shown in Fig. 12C.
In the embo~iment of Fig. i2D, snTTen~r elelnPnt~ 226 are disposed exterior to delivery con~itc 222. In an exernr!~ry embo~imPnt, the s~;rre..~l elomentc are disposed along a side sl..f~ce of each delivery condl~it so as not to i.~t~. re~e with cont~rt between the outer lateral surfaces of the delivery conrh~itc and the wall of the 25 vesseL Again, s~;rr~ ek- .lf ~lc of various corfigl~r~tiorlc may be used, inrhl(ling round, rect~ng~ r, and other cross-sectinn~l shapes.
In Fig. 12E, several additional embo~imentc of sl;rre~-er el~ tc 226 are illustrated. In these embo~i...e -t~, the stiff~oner elPrnPntC have a surface contour which prevents the stiffer-er el~mPntc from blocking flow of agent through orifices 218 should 30 the stiffener elemPntc float outward against the outer wall of the axial lumen. In one embo liment7 slirræl~er el~PnlPnt 226a has a zig-zag cross-sectinn. In a second embo~imPnt ~I;rr~ .~Pr element 226b has a double curve or wave cross-section. In a WO 94/09845 2 1 ~ 6 g ~ 7 Pcr/uss~/o94s4 20 ~--third embo~iimpnt~ stiffener element 226c has a longihl~in~l ridge 242. In theseemb~imP-ntc, a plurality of transverse slots (not shown) may be provided at various points along the length of the stiffenPr elPmPntc to reduce radial stiffnPsc and enh~nce the free flow of agent from one side of the stiffenPr elPment to the other.
S In another exemplary embo~limpnt~ illllstr~tPd in Fig. 12F, 7l;rræ-~-Fr elPmPntc 226 will have a plurality of cut-outs 227 along their length, which may take the form of inrlent~tions along the longitlldin~l edges as shown, or, ~ltern~tively, slots or holes through a middle portion of the ,I;rre ~Pr elPmPntc. Cut ou~, 227 f~t`ilit~tP
flow of agent from one side of the stiffener elemPntc to the other to ensure the agent is not blocked from flowing ~hrough orifices 218.
In a further emboriim~nt of infusion array 216, illustrated in Figs. 13 and 14A, an elActnrnPric sleeve 248 is mounted in guide p~Cc~ge 234, with delivery cond~-its 222 disposed about the l~el;phery of the ela7lo-l-e,;c sleeve. Fl~lo~le~;c sleeve 248 will comprise a tubular ehPmP-nt of a flexible and resiliPnt el~lo..-elic 15 polymer, such as silicon or Ul~ th~h~e. Usually, delivery con~ tc 222 will be fixed to the exterior of el~c~o.--P,;c sleeve 248. In this way, the el~(o,..f ~ic sleeve serves to f~ilit~t~ resilient return of t'ne delivery contlllitc from tne deployed to tne lndeployed poCition. In ~rlriition7 t7ne Pl~ctorneriC sleeve serves to ....;..~ ligllll.P.~t of the delivery conduits as tney are exp~nded so as to m~intAin proper spA-ring between~ acçnt delivery con~itc. W7nile stiffenPr elpmpntc 226 are inrlllded in Figs. 13 and i4, the use of elasLul"e"c sleeve 248 may obviate t7ne need for ,I;rL -;..g eie ..P~ , as the sleeve may adequately IllA~ Aliglllllf~t and provide resiliP~re.
In an alternative embo~limpnt~ ls~tPd in Fig. 14B, el~c~o...~.ic sleeve 248 is disposed ~torn~l to delivery confi~itc æ2, with the delivery cor-d~.itc secured to the interior of the sleeve. Orifices 218 extend from axial lumen 238 through delivery con~ itc 2æ as well as through el~ . ;c sleeve 248. ln a preferred embo-lim~rt the el~ctompric sleeve is co~figl-red so as to ~en~r~lly conform to the exterior contuLIr of the delivery conduits, ~ g the profile of the distal portion of the catheter, as well as accommori~ting the expansion of the delivery conduits.
Referring now to Figs. lSA-lSC, distal tip 228 will be more fully described. Distal tip 228 provides a ",;.~ lly tr~--m~tiC leading edge to catheter 200, as well as f~rilit~tps slidable tracking of c~thetPr 200 over a r~ t~tion c~thPtPr, as WO94/09845 2~ 8S7 described more fully below. In addition, the distal tip 228 provides a seal for the distal ends of delivery conduits 222. In an e~empl~ry embodiment, shown ir. Figs. lSA-15B, distal tip 228 has an axial passage 250 ~lignP~d with guide passage 234 in shaft 202.
Distal tip 228 has a conically tapered exterior to enh~nre navigation of the c~thPter S through a vessel lumen. Usually, distal tip 228 will have a length of 1 to 5mm and rinr ~ lP~I at ~ ;al end 254 genlor~lly equal to that of the outer s--rf~r,e of the delivery co.-d.-;t~ 222, with distal end 252 being a~plox;.~.~tP-ly 30% smaller in ~-~---r~r than lJru~Ll..al end 254. Distal tip 228 further inr~ es a pl-~ y of ~f~ lly-extPn~ing prongs 260, which fit within axial lumens 238 at the distal ends of delivery conduits 222. Prongs 260 thereby provide a seal for the distal end of the delivery conduits and provide the ~h~sio~ to shaft 202 required to plope,ly retain distal tip 228 with the catheter. Prongs 260 can also be employed to retain the distal ends of ~I;fre~.çr elPment~ 226 within axial lumens 238. In one embo-iim~ont~ distal tip 228 may be mol~e~i urethane, formed by a process in which urethane is poured into a 15 mold and the distal end of shaft 202 is inserted into the mold while the ~ ha..c is liquid, ~cllllilLing the ~lleth~le to wick into axial lumens 238, thereby forming prongs 260.
In an ~lt~ tive embo.1im~nt of the distal tip, illustrated in Fig. lSC, distal tip 228 has a trumpet shape wh~,leill axial p~cc~ge 250 tapers radially outward in 20 the distal direction. The outer yel;~kel~ of dist~l tip 228 may be tal,el~d inward near the distal end 252 to f~cilit~t~- navigation through a vessel lumen. The L..~ et-shaped distal tip of Fig. lSC f~ilit~tt~s smooth retraction of the e~p~ncion ll.eillber (e.g.
balloon) of a dilatation c~rh~ter from a position distal to distal tip 228 to a position within guide p~cs~gç 234 ~ cent delivery con~litc 222.
Fig. l5C further illl-s~tes the retention of distal ends 229 of stiffçn~r cle ..~ c 226 by enc~rsul~tirJn in prongs 260 of the distal tip. In this embo~limPnt, when distal tip 228 is to be formed, ~l;rr~.~Pr elem~ntc 226 are pocitione~i in axial lllmPnc 238 of the delivery cQn~lllitc with distal ends Z29 near the distal end 204 of shaft 202. Distai tip 228 is then formed as described above, by pouring a polymer 30 such as urethane into a mold and putting the distal end of the c~th~tPr shaft in the mold while the ulc;tll~ule is liquid. The urethane then wicks into axial lnm~onc 234,e~r~rsul~ting the distal ends of the stiffen~r elPm~n~c.

WO 94/09845 '2 1 4 ~ 8 5~ 22 PCr/US93/09454 Referring now to Fig. 16, manifold assembly 208 will be more fully descnbe~. The manifold assembly in~ des a housing 262 which may be a metal or any of a variety of rigid plastics, in~ riing acrylonitrile-bllt~ np-styrene (ABS), Delrin~, polycarbonate and the like. Shaft 202 ext~n-ls through a flexible polymeric S strain relief 264 into an imerior chamber 266 witnin ho~lcing 262. The ~lo~ ,al end 270 of s'naft 202 is secured about a cylinrlrir~l mandrel 272 formed in hollcing 262.
Mandrel 272 has an axial bore 274 which conn~ctic ~ t~tirJn c~th~t~-r port 210 to guide p~cc~ge 234. In a preferred embo-iim~nt, a diaphragm 275 is mollnt~d in a pro~ al portion of bore 274 near catheter port 210. Diaphragm 275 has a p~Cc~ge 277 which may comFIri~ a hole or slit which el~ctir~lly exp~nric when a ~ t~tior~ c~th~ter of larger ~i~...eler is inserted through it. The diaphragm thus provides a sealed entrance for introducing a riil~t~tion c~tht~r into guide passage 234.
Ch~llber 266 is in co~ tion with agent intro~uction port 212 in Luer fitting 214. The pr~ ,al end of shaft 202 will have circumfelc.l~ial notches 268 providing fluid co.. ir~tion between chamber 266 and agent delivery p~cc~ges 220.
Luer fitting 214 will be configured for conn~c~on to a precision agent delivery device.
In this way, an agent delivered through delivery port 212 will flow into delivery p~C~ges 220 for delivery to infusion array 216.
In a preferred embo~lim~r t of the method of the l.~esenL invention, 20 i~ str~ted in Figs. 8A and 8B, the c~th~t~r is posi~ionPd tr~ncl--min~lly in a body lumen or vessel V, which will typically be an artery. 'l'he vessel will have a wall comprising three layers, int~ln(ling intima I, media M and adventitia A. The c~th~t~r will be position~d such that orifices 34 in delivery conduits 32 are disposed near the L~
site, which will most often be an atherosclerot~c region of st~nocic S in the artery.
25 Usually, a movable guide wire 26 will be used to guide the c~th~tçr through the artery.
A fixed guidewire ~tt~ch~od to the distal end 22 of the calhe~r may be used inct~d.
When the catheter has been positioned near the l~e~t.-.ent site S, the exr~n~inn m~mher 28 is infl~t~c~ with an inflation fluid introduced through inflation fluid introduction port 42 in housing 38 at the pro~ al end of the c~th~tPr.
30 Preferably, e~cr~n~ion member 28 is e~cp~n~ed s--ffici~ntly to bring delivery conr~it~ 32 into contact with the t~e~tm~-nt site S. If desired, ~ t~tion of the vessel may be ~lrull,led by infl~ting e~r~n~ion member 28 sufficiently to expand the interior of the WO 94/09845 ~ 6 PCr/uSs3/09454 vessel lumen in the region of stenosis so as to effectively restore blood flow to an appru~iate level.
Frequently, it will be desirable to impregnate the tre~tmPnt site S with an agent before, during or after such ~ t~*on. Advantageously, the physician may S position the de}ivery conduiLs 32 against the tre~tmPnt site and l c-ro~ll. any desired t~tion wi~hout infilcing any agent through o~ifices 34 in conduits 32. When agent delivery is desired, an agent is introduced through agent introductirn port 40 in ~ro~ al honcing 38, from which it is co.. ~.. ir~tPd through delivery p~cc~gPs 36 to delivery conduits 32. The agent will be infused through orifices 34 to lJ~nellnte the 0 ~ t site S. Usually, the agent will be infilcPd into the l.e~ site at pressures sufficiPnt to attain per-Pt~tion to at least the media M, and preferably into the adventitia A of the vessel.
In an ~ltprn~tive mPthod, an agent may be infilced into the lumen before eYp~n(iing the e~p~ncicn member. After infilsion, or while it is col.~ ;..g, an infl~*on 15 fluid may be introduced into the device to exr~n~ the ex~ ;on member, pocitionin~
the delivery con~l~-itc adjacent the lumen wall. Infusion of the agent may col.l;..ue, or a dir~rellt agent may be infilsed through the delivery cond~-itc to ~)enelldte a L-~t~..e-~site within the lumen wall.
In a sperific embo~imPnt, the mPtho~l may comprice infilcinp an agent 20 tnrough one or more selP-cted delivery condnitc 32 without infilcing the agent through other sPl~cted delivery con-l--itc. Using the c~thPter illustrated in Figs. 3A-3C, the agent will be introduced th~rough one or more agent introduction ports 140 c~ to the delivery con~--itc 32 which are to be used for infilcion. For example, in Figs. 8A
and 8B, an agent may be infilser~ through delivery cond~itc 32a, 32b, but not through 25 delivery con(lnit 32c, by introd-~ring the agent through the col,~syonding introductiQn ports 140 at the ~r~ llal end of the c ~ tr..
In a further embo-limPnt the m~thod may inr~ e infi~cing a first agent through selPcted ones of delivery con~nitC 32 while infi~cing one or more different agents through others of delivery cond--itc 32. Referring to Figs. 8A and 8B, a first 30 agent, such as a growth inhibitor, may be infilsed through delivery con~uit 32c, while infilcing a second agen~, such as an anticoagulant, through delivery conduits 32a, 32b.
This is accomplished by introdll~ing the first agent through the ap~lopliate introduction :2 ~ ~ 6 8 5 7 24 Pcr/uSs3/094s4 port 140 (Fig. 3A) co.-.-e.:lrd to cond~-itc 32a, 32b, while introduçing the second agent through the intro~..ction port 140 connPcted to delivery conduit 32c.
Once tre~tmpnt at a particular site has been completed, drug delivery may be t~ t~i, and, if desired, e~p~c;orl member 28 deflated by withdrawing the S e~pancinn fluid through inflation passage 54. Dilatation and/or agent infusion may be repeatPd at the 1~ site S. When tlc~ P ~l of the site is cornplete, the cz.tllPt~;r may be repositinned without removing it from the body to ~elrul~ t~ti~n and/or agent infusion at a new tre~tment site. It can be seen that the device and method of the lJlcselll invention f~ilitat~ infusion of an agent with or without ~lilat~*on, ~ilat~tinn 10 with or without infusion, infusion of multiple agents cim~llt~nPollcly, direction~l infusion, and tre~tTnent of multiple sites, without removing the device from the body between such tre~trnPntc.
A further embodiment of the method of the invention is i~ ctratpd in Figs. 17A-17D. In this embo-limPnt, utili7ing the agent infusion catheter 200 described 15 above in connPction with Figs. 9-16, a balloon rlilat~tion c~thPtPr DC of convelltio construction is ~nclllmin~lly positionptl in a blood vessel V such that a balloon or other eyr~nci~n ,..~ her 280 (in an ~...;..ll~d corlfi~-~*on) is near a ~e~l...e..~ site S.
Typically"lil~tatiQn c~l~.eter DC will be pocitionPd over a movable flexible guide wire GW. During this step, agent infilcion c~thPt~Pr 200 need not be, but may be, positioned 20 slidably over ~ilatation c~ r DC. In some embo~limpnts~ it would be desirable to position a niiat~tion cathpter in the vessel first, do a ~ t~tion and then remove the t~tion c~tl.Ftr r. Subsequently, c~thPter 200 is introduced over the ~ t~tinrl C~ ,tf r and both c~thPt~s are introduced together into the vessel. In other in~t~nces~ c~theter 200 will be pocitionPd over the ~ t~tion c~thetPr outside of the body, and both 25 c~thet~ls will be tranclnminally po-citio;-pd in the vessel together. The ~ t~tisn c~thPter may then be used to pelrollll rlil~tation as ~esçrihed below.
As shown in Fig. 17B, balloon ~lilat~tiorl c~thet.~Pr DC is pocitioned such that e~pancion mernber 280 is disposed distal to the distal end of agent infusion c~thPter 200. Flcp~ncion member 280 is then inflated using known techniques, ~ t:qting vessel 30 V at ~e~l-.-e~l site S.
F~Cp~ncion member 280 is then deflated ar.d, as shown in Fig. 17C, dil~t~tion catheter DC is drawn proximaUy relative to agent infusion c~h~!~r 200.

WO94/09845 25 21~68~7 Dilatation cAth~ter DC is positio~d such that expansion member 280 is adjacent inf~lcion array 216 in the interior guide p~cs~ge of c~theter 200, described above.
Agent inf(lsion catheter 200 is then positionPd within vessel V such that infilcion array 216 is near Llc~ -P-~ site S.
S FYpancir~n member 280 is then inflAt~d so as to position delivery con~1--itc 222 in ap~osiL,on to treAtm~nt site S on the vessel wall. An agent is then delivered through delivery pAC~Ees 220 in catheter 200 to delivery contl~itC æ2. The agent is infi~ under preSau~ through the delivery cond~litc and through orifi~ec 218 to ~nrl.~tt~ the vessel waU in the region of LI~A~ e"t site S. When lleAIl.~F ~t is complete at the site, agent delivery is ~icco~tinlle~ and exp~ncion member 280 deflated to return delivery cor(lllitc 222 to an undeployed position as in Fig. 17C. If further tre~trnent is desired at the same or different site, dil~t~tinn catheter DC may be extender~ distal to infusion c~theter 200 to the position shown in Fig. 17A. Dilatation and/or agentinfusion may be repeated at the same or a different site.
To f~cilit~te longitlldin~l positioning of infilcion catheter 200 in a vessel lumen, as well as to assist proper axial ~lig.. P.. ~ of the e~p~ncion ,.. e.nbGr (e.g.
baUoon) of the ~ t~tinn c~thlot~r with inf~lcion array 216, radiopaque l.~LGl~ may be provided on infusion c~thet~r 200. In a ~lc~Gl~d embodiment, shown in Figs. 18A-18C, radiopaque m~Lels 282 are disposed on one or more of stiffer er ek .~ 226.
20 ~rkPrs 282 are formed by, for example, plating a radiopa~ue m~t~l such as gold or pl2~ onto stiff~nPr elpmpntc 226. Dil~t~tion c~th~ter DC wiU also have a radiopa~ue marker 284, which is typically formed on the inner shaft 286 of c~thlot~r DC in the interior of eYp~ncion el~nent 280. In one embo~iment shown in Fig. 18A, at least two IlldlkGl:i 282 are disposed on ~I;I~..er elemtontc 226 in a central portion of 25 infi~cion array 216, the IlldlkGl~ being sep~r~t~?~ a rlict~nce from one another usually about equal to or slightly greater than the length of marker 284 on ~ t~tion ç~thet~-r DC. In this way, by vic~li7~*on through a radiographic im~ging device, Ill~ls 282 f~`ilit~t~ axial ~lignmPnt of expansion element 280 with infilciorl array 216 by ~ligning t~*Qn catheter marker 284 between markers 282 on sLirre..el el~m.ontc æ6.
Markers 282 filrther provide visual in~ic~*on of the locahon of infusion c~thet~r 200 within the vessel so that infusion a~ay 216 may be poci*on~d adjacent to a ~ u.,.
site.

Wo 94/09845 2 1 4 ~ 8 ~ 7 PCr/US93/09454 Alternative embo~imPntc of radiopaque markers 282 are illn$tr~tPd in Figs. 18B and 18C. In Fig. 18B, marker 282 is disposed on a distal portion of stiffenPr e~PmPnt 226. In this way, r~ t~tion c~th~tPr DC and/or infllcion catheter 200 are axi~lly re-positioned relative to one another until marker 284 on the ~ t~tion S r~thPter is exposed on the plo~unal side of marker 282. In the embo-iiment of Fig.
18C, marker 282 is disposed on a prox,lllal portion of stiffener elPrnPnt 226 wlleltl)y the r~thPt~rs are axially aligned by positinning riil~t~tion catllt~r Ill~h~r 284 distal ~o ~h~;r 282 on the sl;r~ elPment While the above is a complete description of the preferred emborli..,~l"~
10 of the invention, various ~ltPrn~tives, moflific~tinns, and equivalents may be used.
Therefore, the above description should not be taken as limiting the scope of the invention which is ~efinP~ by the appended claims.

Claims (30)

WHAT IS CLAIMED IS:

1. Apparatus for infusing an agent in a body lumen, the apparatus comprising:
a catheter body having a distal end, a proximal end, a guide passage, and at least one agent delivery passage;
an expansion member movably received within the guide passage of the catheter body near the distal end; and agent delivery means disposed along the catheter body near the distal end and in communication with said agent delivery passage.

2. Apparatus for infusing an agent to a treatment site on a wall of a body lumen, the apparatus comprising:
a flexible shaft having a distal end, a proximal end and first and second passages therebetween;
an expansion member disposed at the distal end of the shaft, the interior of the expansion member being in fluid communication with the first passage;
at least one laterally-deflectable delivery conduit secured at the distal end of the shaft adjacent the expansion member, the delivery conduit having a plurality of orifices on a lateral surface thereof and an axial lumen connecting the orifices to the second passage in the shaft; and an axially rigid stiffening element disposed axially in the delivery conduit.

3. Apparatus for infusing an agent to a treatment site on the wall of a body lumen, the apparatus comprising:
a flexible shaft having a distal end and a proximal end, with a guide passage and at least one delivery passage extending axially through the shaft, the guide passage being open at the distal end;
an inflation tube slidably disposed in the guide passage having a distal end, a proximal end, an axial inflation lumen therebetween, and an expansion member attached to the distal end in communication with the inflation lumen, wherein the expansion member may be advanced distally from the distal end of the shaft; and a plurality of laterally-deflectable delivery conduits attached to the distal end of the shaft generally parallel thereto, each delivery conduit having an axial lumen in communication with at least one of the delivery passages and a plurality of orifices on a lateral surface thereof, wherein the expansion member is axially positionable adjacent to the delivery conduits for laterally positioning the delivery conduits in apposition to the treatment site.

4. The apparatus of claim 2 or 3 further comprising a plurality of fluidly independent delivery passages in the shaft, wherein at least a first of the delivery conduits is in communication with a different delivery passage than at least a second of the delivery conduits so as to allow independent delivery of agents to the first and second delivery conduits.

5. The apparatus of claim 2 or 3 further comprising means for maintaining relative alignment of the delivery conduits during lateral deflection thereof, wherein said means resiliently biases the delivery conduits to an undeflected configuration.

6. The apparatus of claim 5 wherein the alignment maintaining means comprises a stiffening element disposed axially in at least one delivery conduit.

7. The apparatus of claim 2 or 3 further comprising a flexible distal tip having a proximal end secured to the distal end of the shaft, an open distal end, and an axial passage between the proximal and distal ends aligned with the guide passage of the catheter.

8. Apparatus of claim 2 or 3 further comprising a housing having a plenum at the proximal end of the flexible shaft, said plenum being in fluid communication with each of the delivery conduits.

9. Apparatus of claim 2 or 3 further comprising at least one marker on the flexible shaft and at least one marker on the inflation tube, wherein said markers are aligned in a predetermined manner when the expansion member is aligned with the delivery conduits.

10. Apparatus of claim 2 or 3 wherein the delivery conduits are separated from each other so that they can move apart as the expansion member is expanded therein.

11. A method of delivering an agent to a diseased treatment site on an interior wall of a blood vessel, the method comprising:
positioning a catheter in the blood vessel so that an infusion array at the distal end of the catheter is disposed at the treatment site;
positioning and expanding a expansion member within the distal end of the catheter to radially expand the infusion array against the treatment site, the expansion member being fluidly isolated from the infusion array;
delivering an agent to the infusion array; and infusing the agent into the treatment site through a plurality of orifices in the infusion array while the expansion member remains expanded and the infusion array remains in contact with the treatment site.

12. A method as in claim 11, wherein the infusion array comprises a delivery conduit disposed adjacent a lateral surface of the expansion member, the orifices disposed on a surface of the delivery conduit.

13. A method as in claim 12, wherein the infusion array further comprises a plurality of delivery conduits disposed adjacent lateral surfaces of the expansion member.

14. A method as in claim 13 wherein the agent is delivered through a plurality of separate delivery passages such that delivery of the agent to each delivery conduit may be controlled independently.

15. A method as in claim 14 wherein an agent is infused through a selected delivery conduit without infusing the agent through at least one other delivery conduit.

16. A method as in claim 14 wherein a first agent is infused through a first delivery conduit while a second agent is infused through a second delivery conduit.

17. A method as in claim 11 wherein the expansion member is attached to a dilation device removably disposed in an axial passage in the catheter, the method further comprising the step of positioning the dilatation catheter in the axial passage.

18. A method as in claim 11 wherein step of positioning the catheter in the blood vessel comprises guiding the catheter into the vessel using a guidewire.

19. A method as in claim 11 wherein the treatment site comprises a atherosclerotic region of the blood vessel.

20. A method as in claim 19 further comprising expanding the expansion member to dilatate the vessel.

21. A method as in claim 20 wherein the step of dilatating is performed before the step of infusing.

22. A method as in claim 20 wherein the step of dilatating is performed after the step of infusing.

23. A method as in claim 20 wherein the step of dilatating is performed during the step of infusing.

24. A method for positioning a catheter over an expansion member, said method comprising:
visualizing a target location in a body lumen;
introducing the expansion member though the lumen to the target location;
moving the catheter relative to the expansion member; and aligning a marker visible on the catheter with a marker visible on the expansion member to position the catheter and expansion member in a predetermined relationship relative to each other.

25. A method of delivering an agent to a diseased treatment site on a wall of a biliary duct, the method comprising:
positioning an agent delivery catheter in the biliary duct so that an infusion array at the distal end of the catheter is disposed at the treatment site;
positioning and expanding an expansion member within the distal end of the catheter to radially expand the infusion array against the treatment site, the expansion member being fluidly isolated from the infusion array:
delivering an agent to the infusion array; and infusing the agent into the treatment site through a plurality of orifices in the infusion array while the expansion member remains expanded and the infusion array remains in contact with the treatment site.

26. A method of delivering an agent to a diseased treatment site in a lumen of the genital-ureteral system, the method comprising:
positioning an agent delivery catheter in the lumen so that an infusion array at the distal end of the catheter is disposed at the treatment site;

positioning and expanding an expansion member within this distal end of the catheter to radially expand the infusion array against the treatment site, the expansion member being fluidly isolated from the infusion array;
delivering an agent to the infusion array; and infusing the agent into the treatment site through a plurality of orifices in the infusion array while the expansion member remains expanded and the infusion array remains in contact with the treatment site.

27. A method of delivering an agent to a treatment site on an interior wall of a blood vessel, the method comprising:
positioning a first catheter in the blood vessel with an expansion member at a distal end of the first catheter near the treatment site;
positioning a second catheter over the first catheter such that the first catheter is slidably disposed in an axial passage in the second catheter, whereby an infusion array at a distal end of the second catheter is near the treatment site with the expansion member of the first catheter positioned distal to the distal end of the second catheter;
expanding the expansion member to dilatate the blood vessel at the treatment site;
contracting the expansion member;
axially aligning both catheters such that the infusion array is aligned with the treatment site and the expansion member is adjacent to the infusion array;
expanding the expansion member so as to position the infusion array is adjacent to the treatment site; and infusing an agent into the treatment site through a plurality of orifices in the infusion array.

28. The method of claim 27 wherein the infusion array comprises a plurality of delivery conduits secured to the distal end of the second catheter, the delivery conduits having axial lumens for delivering an agent through said orifices.

29. The method of claim 27 wherein the step of axially aligning comprises aligning a radiopaque marker on the first catheter with at least one radiopaque marker on the second catheter.

30. The method of claim 29 wherein the radiopaque marker on the second catheter is disposed on a metallic stiffening element in the infusion array.