Note: Descriptions are shown in the official language in which they were submitted.
2~ 3~g
~'0 90/1~636 PCI/Al~'9~/002~2
- ~ r ~ - o - - ~ , c r - - r c e
^ ~ e !_ O c ~ he T nve~ cn
Th~s .nver.~,o~i -re ~a~es ;5 ce~v- ces _^~ ~o~ov_d~g
~oe, cu-aneous æccess to the bo~, anc' mo-e p2r~ c~12~
mate. iale ~nc s ~ res a~ cabi~ ~In anchc s~.c`. cev~ ces
with~n she boe:v ~or sub5;2~ 21 perio~s Oc .~.e.
~e~ c- ~ ~t ~ o~. o ' ~._ ~ ~
?erc~ ~a~.ec~_~ 4Cce~-- ' 9 ^~ e- . e~ e- f ^. t~.e de!ive-~,
lC Oc ~ erape~~ ~ 2s~:~;s, ~~.e ?~CV_sio?. c. D ~ e,, ~r` cz', pne~mz'~-
or si:~ 12- .rn~_`~ses or ~he re~novei Oc e~co~es~us'y or
exsce:~ously Jr.a~ 2C~UreC r.2~er.z' . The `:leb` 1 ity Oc L;:lo~
access devices (COJ.DCnly -e~'e-~e~ to as c~theters) to bcn.d
effec~cively to or ~o ~ w~ CO~ _O~s ~ss~e,
15 pa~lcular'v a. t;r~ de~:na:/e~.derma~ _~er'2ce o~ ex't site,
n e f2s~i~r. a.;cloco~s to no~ r2~Ls5-esse~ c~ ~:n~ro~en s.~l
.'~c~ ates ecress c' :~c.~e-ne. 'l~_~ds ar~.c. i-~.g-ess of
biologica pa~hogen.s.
P~t..o~ en ca' ",~ ~le'- e ~ec i,.';a,..~z' i c.. a the e~ s te
20 leacs ~o ~iscor~. ort ~n^, ~epe-.~,n~ ~po~. 'che seve. ity, a~
aest~etical~v :3~?ieasa-t a~l~ezra;lce and oc~ou~ . Such
~nfectlo~ le~ ~nche~ke~'. o~ if it p-o~esses in a~
ur~co~.trollabi~ ~as~.ior., h'i~ 1 t_acl; ~lor.~ ~he in v~vo po~tion
o4 the cathe~e~ ar.c Ca.. le?- t~ sy5te-.i^ ' r ~ectio~ o~
5 i;~'ect~or o' o;le or ~o~e o~ the -ecipier.~s ~:~tern21 orsa~s.
Con~inuou~s a~ 'a~c~ e-~ c-.ec ~.alysis is æ~. exa.
0~ G the~Gpy -ec~ i-.o ch~c._c s~able pe c~aneous a~-esC
2 ~ 3 ? 3 ~ 6
~ ,0ll5636 PCT/A~90/002$2
_ ~ _
Co~.ri~.~o~c a~ lG;o-S pe- ~one~' c_a'ys~s ~e~u~-es
ap?ro~r.,e~e`~ ~ 'itres c' hy~er~o..,_ s__~~ o.. D^ ~..5 ~' ' le~
ar.d be cr~_ned ~rc~. -he pe-i~oneO: cav_~v o,' the pz~ie,. four
Simes p~- ~ay. Fl~i~ 2c-ess ~ the pe-itcneum is ~aine~ vi~
a ~-c~aneously posi-ioneA ca~heter. ~etie~-c, wi'~ b~
mz~tzir.e~ o.-, 'kis thera?y ur.~'i s~ m~ as they re~ove-
~id~ey '~c.-~ior., a-e g~ve~. a ccr.o. ~ An'~, ~ acec o~
~.lte~r.~ t~.e~cr~es ^~ ~.e~ 'i F~ r~ls O~r
ma~..ta'ned c-. co~.ti-,uous a~ z~c-~, pe-i~onea' ~ia'ysis ~c
~0 ~hree ~o ~ou- yea.s z'~h~_ n so~e patie~ts have bee~ o., he
t~era?y ~o_ as 1O~5 as lC yeo-s. ~Y.~. site an~ cathete-
tunne' _r.fec~ior. a~.c pe-_~snit's 2sso-_a;ec w ~h a poorly
main;a~r.e~ exi ~ si ce has bee~ c cause c cor~sidera~le
~o~b~d~ty in these patients who ~-~m.be~ a~o~.im~tel~,~ 50,00
li w~ridwice si~ce l99G.
'.. ~he ~ r a ~en~ has. .he~efo~e, foc~ssed
~or. ~ he de~z~ iec cor.s~ructio- 2-.~ co~?os~on o~ tha; F~-
o' the -~e~c_~aneous access dev-ce w~.~. r: ~e~ai~s ~ co~.ac~
wl~h the ~6- s~r. laye-s fo- e~:~e~.ie~ per~o~s Oc t~me when
.20 ~he ~e,c~ar.eous acoess device is ~n use.
Particul2-ly the p-lor z t disc_oses var~ous for~s o.
cu~f h~; ch en~a~e the ~e~phe-y o~ ~u~_r.s a~ .e '~e a~ t~e
: poir.t where the tubir.~ ~r.~e-s the body in su-h a manne~ as ~o
~: provice a physical ~uf~e~ be~ween ~he s'~ aye.s 2~ .hc
25 entry p^ rt an_ the tub~ r.~ ma~e-ia` ' ~sel~ .
A COl;~ Gn fcrm Oc c~Cc Jr,~e._a:, ~acron ('r~ace ~5ar';1, is
~sclosed ~ ela~ion ~G a relat~ve y COJr.~ie~ "rP-air.e.~"
s~--~c.u-e ~ US ~,2?6,09~ (3O-sa-.~ e; -'`.
~WO90~l5636 PCT/A~90/00~
293~3~6
~c, ;.6~_,5~ c Lee et ~1) cis~oses ~ re:~ e:v
c~r;~te:~ cu'' w~.~c~ c'~_~es ~ a~ '.t ~e ~e~me~ 2 _'S~
a~ e~ ~ e~ w~'' a~ o~ tn~ w.~:c~
s~r.ounds ~;5 ZS to he~s c~c~_- th.e c~ 4 ar.~ .be _r. plzce.
~he ~s: por~ion _r,c~udes a pl~ral_~y o~ Aoles adepted ~o ~_c
~he ir.~row.~. Gf b~Ay ~terial.
T_. c~r~er; practice, cert2i~.'y ~r. Australia, surgEs~s
h~.re ~pte~ ~O~ c~.~.F'ici~ s_oA ~
c-.a.ae~e-_st~ C5 C ~ tre eY.?er.Se C. F~ssi~;e ~.e~_ur~ t~ 'or.s
0 '~-~ so~ _ss"e C2-,-'~CZ~'O~.S. Spe~_f_-z:'y, ~ccess .5 V'c
a s'l'con cat~.e~e~ w '.~ a ~acror. (~racie r.a~'-) felt c~
Lr~'ace~ ~r. the s~bc~ar.~e.., ~ 5 t_ ~ r~ e~ es r-or ~.e
s~. ex~ site. ~ s 'c-2 o' s_~cu~aneo~s ~'~C4 is ~esi~ne~
;o z~cho~ the cathete , ~-cvi~e ~r.~t5~_ ~ ' sz~on ~n~,
-heo-e~ical'y, ~re-~en~ e~_~err~c'~ ~owr.~ro~ .. r.~. acc't'c~.c'
cu~' is us~z'ly place~ severc` ce~ e-res dee~e. be~oh the
s.;_r. s-_rface ~o r~eve~ ea';z~e o_ d_~ysate fro~ the
pe~ ~onO~
he ~a~cr fa_lu.-e ~.odes C4 ~hese c~-he~ers r~_ate ~G
so ~ ~issue cor.;p:ic2~ior.s su;h Z5 eY.it S' ~e in~ec~o~ a~.~
cu,r e~:trus'sr. w~.~c~. is ~.y?othes~se~' to be p~irari~y d~le ~o
po~- co~.~a~bi,~ty 04 ~he Dacror. cu~ and/o~ e c' ~he
c 4~ to 2-eve~.~ s r.uc fo ~tior..
~he Dzc-on fe't cu~f is a wove~ s~~uct~-e z~, 2s
2; suc~, is no~ a t-~ly ~orous s~ruo~u.e ~ t~.e sense use~
this spec_~ic~or..
WO 9011C,fi36 PCr/AI,:901002~ ~
2~333~
4-
~ he ~-ic,- a~ he ' 2~ ~ C pe~c~_ ~z~.e-,~s a~.c
subcutaneous cuC~ devicGc z_~o~ler~e~ tt.e~ so~.e a~te~ Os
neecs -o be pa~ tc t:~,e rc.cs..y c~ ~he cu f mate-ic`, z~
;eas ~ 2- the c~f f /s~i.. ir.~e.face. ~ ~a?er e-,.itled
"Pe_s.ar.e~.t ?erc~aneous De~ ces" ~ Ja~a.5~, 19~; ~ssue
(Vol.5) ~ ~RC _ itica'~ Revlews ~n B.oeo.cinee~~r.; provides G
co...p~eher~s~ve summzry, as 2~ th2~ ~a~, c. such dev~ces zr._,
~t pa~e SC~ et ce~ o es ~lcel~ p-~ _C`_lZ-_'J' 10 ~~.e ~,a;~er
of per_u~aneouo d~ e-s'.;~ er~c~ior.. ~ os~y is
speci.ical y ~_scusse~ he~
~ /US~5/~18~9 ~066~0;?29) ~c Ya~amo~o e~ a' ~scioses
a p2-~ cula,, d_s.e~ ,;e cuff s~r~u,e ar.d r.otes thal t~e
surfaee cc the cu~ struc~u~e ~ust have tissue seali~s
proper~ies "whic~. ca~ b~ co~fe-re~ by (:~ the a-~ch~,er.~ o~
porous, ~issue insrow~:~ romoti~g m~ter~ . s~eh as wove~.
4el~s, 2~C ve'ours, ~ex~ure~ riGlymers~ ~r.~ foa-, c~ sp-~oe-
li~e mzte.`zls. (~ ~he s-:r~ace te~..ur_n~ o' t~e sleeve
~a~e-ia' ~y high ene~y bo~oa-dme~t o~ sz1:in~ o~ ~.e~hods:
~3) the att2ch~er.~ o~ ;r.corpo~2tior. 5' ~issue a~:~esive
biomolec~les s~ch as lec'ins~". Ya~a~.ato uses ~he te~m
"porous~ . a 'oose, brozd se~se.
E~0164~g6 ~o The-~edics d~scloses ~ s~-ucture h2vir.s
eavities whl~h a e ~r.~conne~ted ~y a ~o~ou~ pcth . .he
~PO~O~Y" GL s~ch c. s~-;c.~:-e i5 somewha~ c~
~5 Generc~ can be sa_d th,~- the p io~ a-t ~ icztes
t~ the so'~ior.s ~5 t~.e p-o~lems c, obta.r.in~ a
s~tls aclory a~cho~i~g syste~ fo~ 2 ~e--u~aneous 2ccess
2g33~
WO90~15636 PCT/A~I90/002~'
_ ,_
S~ ~e ~ e ~ 6a~ c~ e~:~ty c. ~e^~,e~-~a1
s~ c~u-e of eu'-s use~ z~ ,hC bocv er. l ~ co_~.: fo- s~h
cet~es a.,c~ ecse- cor~'e:it~ of c;.e..~c~.' cor,~os_t_-.. t~
che~.~cc! trea;m~-~ Oc the s~i~. cortac~ o~tio~.s Oc those
-- dev~ces. Ir. practice s~rseor.s have se.-;e~ fc- relat~velv
s~mle s~uc~_res wh~ch ancho- reliably anc are e2sy to
ir.s t all, but ~h'ch s-''' h-~ve tis_ue ir~e~ a C ~ . on a~d
infect~' or. p-o'~'em~ and S~hG-eCO-e -e-u~ c o ~c.~cn. e~ s ~-
ca~e.
~ s a~. c~,ec: c ,,.~ 5 irve~ o~ c~ide ar.
~prove~ ye~ s~r~.~ y co~lst,~c~e~ pere~a~.eo~lC ~~cess dev~`ce
wh~c~ bor.~ tc cr b~r.~ w ~ h cont~guo~_ ~issue to ~
s~f'c~er.~ ce~ee zr.- in s~ch a wzy so 25 ~o ove-come ~o at
leas~ so~.e exter.~ the ~-c_lems assoc.z~e~~1ith p~ior a~S;
catheters ar.~ the~r ~:~chor~ns sys~ems.
Su~.ma~v c~ ~n~ 'nven~or.
Accor~_n~ so the ~ er.~icn ~here ss ~rov~de~ a
pereu.2r.e~ cess c~t~_ce co~?-is_r.s z o.~ ada~ted ~o be
passed t~.rouS~ the s'~n ~o def~.e ~ portc' to an~ _ror- the
~0 body anc a po-ous cuf o~ ~iocom.pat~ble mater~21 aro~r.~ the
cond~t: s2id b~oco~ t~bie ~ate.~l h~v~ .omogeneous
~r.~e~-o~.~ected porous st~uctu-e o' t~e ty~e which can be
p-oduced by ~.e reria~nefor. tech~ ue; s,~ c~_'' a~ap~ed ~o
be s~rs,c2!1y placed so as to zn_ho- s2'J csnd~ with~. tr.e
body as a resu't c' tissue ~r.~rowth ir.~- sa;~ cu.~.
The po~es o: the cu'' ar~ _r.~e~cor.ne-t~nc ar.~ 2n
ar.alosy between '~. s pc-sus sc-uc~ure m~; be m~de, for
` ~090/1~636 PCT/A~9~ æ ~3 3 3 g
~,
eY.~, lr, W' ~ t~.e s~u~-.u~e c. ccnre` _G'''5 0~ s~on~5~ bo~e, t~.e
t-a~e__~ce~ e s ~~u:;~_~es ~ n ~.is 5 ~c; or. be ~ n.~
cor.st-u:~ed o~ the bioccrpG~~ble 3ate-ia~ o~ .ir.~ a 7G.~lce
on w~ h tissue is ~ recte~, rs~rru~e-~ an~ s~ppo~te~.
S~e c~ ~ o'-~he ~ve-~:icn ~ay be man~C~c.~red by
establishe~ techniques suc}~. 25 tne repla~.~ne'or~ process in
whic~ t~.~ s~eletal st~c~res c' ~a-_r.e .~.ver~e'~ra~es are
se~' zc tar~ c.
~ he s~ .e ~ro-~acer b~,~ t:ee -e?'ar..ir.e~crr p~ocess hcs
been desc. ~` by ~s c~i~~r.~~o~ 25 C "P:'`OC'iC rb~-.'m~
surface" ~w~. -e ~.A. II-VZi~G~ On O' SmG~ ame.er Gr2~t
Pe-amete~s usin~ Re~ia-'neform vas~ui~ os~hes~s" at pase
3;5 i-. vasc~'e- G a~t nG, e~.. Jchr. Wr~gh~, P~S.G., Inc.,
Mas~acnuset~s, 383). Su-h 2 5~C2c' ' S ~t~C~ ~n the sa~e
art~cle ~o divide sace 'n~c ~wc ~nte~pene~rat~n~ networks,
.
eac~. h~vin- pores an^ i~e-co~ne:;~ons betweer. tne po~es oÇ
essent~ t~e same c~er.sic... mhe re~l~m,nefo~^m process
: uses the ric:o po~ous s~eleta~ s~-.~c~ure o~ seleoted ma~.r~e
~pecies as e ~em~late ~o ODt~ ' n ~e desire~ ~orous netwo ~ b~J
the p~ocess c_ ~ ng the void spaces in the s~eleta
structu~e ~ith the ~esire~ biccorpat~_'e materizl an~ the~
etchi.~g away the s~eletzl structu-e itsel to leave only the
b~ocomp~t'ble mate~ial. T~e process is charac~erised b5~ ~s
abil;ty ~o p~oduce po~o~s struc~ures o~ the abo~e des_~ibed
type. ~h~oughout th.s spe~ificatic~ t~.e use o' the ~erm
"homo~e.~eouc, i~te~-~n~e~tec ~o-o~s s~.uc~u~e1~ h_~l be use~
to denote a pcrous s r~oture ~s Ges~~ibe~ b~ W~._te a~
2~3~33~
WO 90/1~636 PCI /~1~90~002~2
-7-
~a~,2~ ~ cc b~ r"- r~ .ce- ~ e E~ ~ia~ .e~or~ ~. oc~s~ .
A ~".o~c..i~ ar:e c' c se~~ior. tho~ ch 2 '~00 n!.`C-C., po e
s`7e 5~-UC-U~c ~o~ce- b~ ~he -C?~ar.~r.e~G ~r. p~ocess i~
re~ro~uce~ in ~ig . 3 o' th~ s svecif c I or. . ~he seade- of
_5 spec~ _ca~c~ s eiSO .e e.rer to cther i' 'ussra~o~.s c'
su-!~. porous s .r~c~u-es pro~uce by the :e~ r.e~o:- pO ocess
a5, fot~ e~a~ ,le, _17us~-a~e-' r ~ pa~e ~75 o~ ~ om6~e-_~5,
Yo ', ~, J~~ 1, h~he ~e ~ 2 ~ . ~c~ ~ 3 ~ ~ c ~ . c ~ ~--c ~,c
~he p~ecurs~. ..a;e-ia: ~9 showr ~ sec~.G:I ar.d -als~ ~c ~ ~ç.
0 G~ page :~ c' -~*mz~~ ~, " V~ ,ul~ 198~ e
s .-..uc~_-es a~ e avzilabl e corr.me~ c_a' 1~ ~-or.. I:~te-pore
'r,7;erna.~0nc' r.e. ir. _~ inC, ~a'i orni~, Ur.-ted S;a;ee c.
Ame- ' ca .
Pre~e~ably, the rorous cu ' is :~a~e o~ me~ cal g~ade
15 s ~ ., i cor.e rubDe~ _s pos _ . ~ o ~.d e ~ the- subeu ,.ane~-:s 1~
(u:~der ~h6 s~ .) or ~e.~u~aneous'y (I.hrough tr.e s'.;ir.` t~ereby
c;low~3 ~bro~ a-.~ eice-.~a' ~ssue i~Lrow:h ir.~o ~he pores
r~e~ 5tir.s i-,~ia..: ar.'y:osic a..~ t_ssue slasil~~y ~eeded ~o
preYer.~ ~r.fe_~ on o the s~ro_n~_~.s an~ u~er!yir.s tisseC
a-,d~c- avulsion zrd ex~e~ o-isa~'c. o~ the c~ r~,
I~. a f~-the. preferre~ f~r~, the porous c1.~ is ~ad~
fro~ hyd-oxyapa.~te or t~?niu~ .
~ alte-n~ive pre.erre~ fo,m, the p5-OUS C__c is
3ace from ~ ocompat~'e ma.er.e~ com~.is'~. one D- more c'
s_'icone rubbe-. se~ ri~ c'y~-e~.ar.e or o~h.~ so'~,
elastome~_c ~.a~e~
The s~7e z-.d d~s~ga o~ l~.e c~C~ ~ - be ~e~ender.~ ~pO,.
WO 90/~636 PCI/A~O~O`~ 3
~he si-e c~ ;h.c co~.dui ~ ~~Gns ,-essi-., tr~e skir.. .Io~eve~ e
l~nç~ ' ran~e ucu~: y f-o~. or.e to sever~ times t:~e
ei:ter~a' ~ 2me~er o' ~h~ co~ he t;.,ck~ess c~ ~he ~-,c,
~2~.~ b~ vzr~a~'~e dever.~ ~u upon po-e si~e and 2pplica~c-..
Pore s ,ze ic se ~ected such t;hat :t wili a' low in5sow r.
asl~ nur~~rin~, Of ~:` b~rcbizsts which lzy down colla$e?. fo~
'i~ro~s t~sue to ar.ky1ose the cor.du t ~hich the ?orcus
mater~al sUsro~Ac.
Prefer2blv, ~he pore size o the cuCc (tha~ ic. tr.e
averz~e ~ia~.e~er c the --egul2rly shape~ i..te~co~h~ ~ir.-
; pore~ w~hin the c~ te-ia!) is ....... the ranse o' 3v t~ 5~0
u~ o~e pre'erc~'y the pcre size of ~he c~ff m~er~G! !ies
; ir. the rance ~5 tc ~00 ~ o~.etr~ ar.~ yet mo.e p-efe~ab's~ in
the ranse 100 to 22~ ~ic~ometres. A. p~-~icu12~ pre~e-re~
fc-~ of the ~nve~ o~ has ~ po-e s~2e o' ~pproxi~ate,y 2
c-o~e ~,r~5,
Tt ~ 5 21so ?refe rec ;hc~ the orosi~y o~' th.e CUCc
(tha~ is. the f~a-~o. cc bul~ vo~ume o~ the ~ate~ial
cc~u~ied bv vo~ds~ .s g~ea.e~ than ~C~. ~ore ~referab'~
~s desired tha~ ~.e pc-os'ty o~ the c~ff ma~erial l~es _r. the
san~e ~$ to R'i%.
P~efe~a~' y where elasto~er~ mate-ia7s are used fo- the
bio~o~pa~ble mate~ial ai~ comp'iance is in the range o' 2:
~o 8; o- ~.o~ pre~e~a~y ~ to ~O Sho~e A po~nts ~ased on
s~2ncar~ ~ST~ ~es;s, Fio-e pre~era~ls~ _n the ran~e ~5 ,O ~e
S~.ore A po_nts an~. ye' ~Dre p~e_erab'y, zippro~.~mate'y 4
Shore A points.
W090/t5636 PCT/AU90/o~ 323 3 6
e~_rs~ar.ceC ! ~.c :r~e.- co ~c~ves o~ ~c~ve s~
~ p~o~e t.re ~ ow~.. ~ . ss~ 2~ nh.~b~ th~
grow~h. c~ bac~e -_ ~.a, b~ cs~oc 2te~ e s~~~G~es c
ir.te~s~ices cf ~h,~ po~es. ~ ssue ç;ow~h p.omoters w~ll
~.r:uce t~e che~.o.~ot_c ~ac~o~s suc~ cs p ateie~ de-'ve~
~row~h fa^~
The su:face o~ tr.e ro-es can be ~ .'ie~ tc ~m~rove
t~ n~.ate ~_~z-~ t~,~ e~ , r! b~ e~ . a~
~.~c oP~ '; t~ S-- ~.ec~.~e~.~ w~:. ~olys yccl c 2ric.
~ab~le su~s~ar. es s c~. as gro~ h 'CctC.5 car. be p_ace~ h'~
~he ~o;res ~. 2 s~c_~ing ~eium s_ch as c coi'age~ oe~l.
Rob~st b~olos~Cc' 2:~1ve s~ec~es a~c ~bs~ces i~ te:~s o'
the_~ ab l i ~y . o ~ ths;2r.~ subsecuent c;e~.~cc~ pu'ation
. ~y be ~-zfted 'o o~ h'~'~.' r. th.e ~lyme~ faee by a v2~ie~y
o~ che~.ical tec;~ es suc~. ~c ~iasmc ~r~'t_~g o~
incorporz~io.. ~ -h~ po yme: F~ o c~'f ~cr.uC2 - ~ e.
G.~f~r.c ~c~ e.c~~,~as~ covclen~ or ~o-e 'a~ile ~nter~olecula~
zt~rac~ions su_:~ zs t.~ose ir.vo!v~ .v~:osen bor.~ ns, ~ipole
inte~ctions ar.- Var. de~ Waals 4Orces.
I~. a fu~r.e- ~oz~ fo~. Oc ~he _~ven~ion the~e is
p~ovi~ed a method o~ ~o~ing a CU44 from bioco~p~ti~le
ma~e-.~' for enclos r.~ ~ co~ for ~he pur~ose oÇ a~chor~s
~ai~ con~uit w ':~_n s'i~. laye-s an~ prC~Ctir.s a biOiosicâi
sea'j S2~ me~hc_ cor.p~ ormi~ 2_~ b~oco~pztible
~ate-ia' ~r. s~oh a ~an~e~ thz~ ^ s st~ct~Ye i~ludes
plurallty o~ po~es w~ h are h shly i~.tercon~e~te~.
WO 9~/1!;636 . PCrtA U90/002~2
2~333~
--10--
~ -e~e-~'y saic` ~,e;hc~ ~c_~cee us~ Or .~e
repla~ e'or.~. p-oces5 ~c p-od~-e sc_~ b~ooompa~ie ~.z;e-_G'.
~ .~ ye~ fu~s;r~e~ b-oa~ fo-.-. o~ ~he ~ve.~~~c~ t~.~.e _
~rovi~e~ ~ .issuC '~.te:~ce whe-eir~ a ~ssue se~l is 20~e~`
betwee:~ a CO~`lit anc' sl~r. i~.te-,ace, s~ tissue ~n~e-.ace
co~.p-_s rg b_~com~zt_~'e ~a~e~ial ~ade ~y -he replar.inefc~~.
process whe~e~y ~ ~tr~ c~re .~a~ing con.-o;led porosity ~d z
r~ornpliar;c~ ~n ~ ~rese~ecte~ -zn,e ~ t_ine~.
~ ~e~er~b'~ sa ~ poroci-y (.:.a~ i~, th~ fr2ct_0~ c^ '~
volu~.e~c~ t;~e rzse~_a' occupie~ by voids) ~s çre2le~ ~h2-. ~C~
ar.d r~ore ~re~erG~ly i~ e rar,ge 2'% .o 85~ eCe-ablv wr.ere
elas-o~.e~c mzleria's ar~ used for ~"e ~ cco~.pz~ib'e m~e~s z`
sa~d cor,~l'zn~e i5 _n the rar.g_ o' ^: lo 6~ S~.o.e A ~oi~ts
based on s.~n~zrd AS-~ tests, r.o-e p-e ~-c~ e ~cr.ge ~5
to 45 Shoro A ?oi~s an~, ~e~ ~ore ~.e~e~~ , a~pro~.imc.oly
~0 Sho~e ~. ~c~ s.
3 e R ~ 5 . . ~ Gh ~ c s
'~; o~Ge- the~ .~.e i?.~ea-io~ ~a-~ oe mor~ reaci'~
unàe-s~ooc ard ps- .nto pr~:'ic21 e''e-:, re~e.ence w_l: no~
be ma~e ~_ ~he accompanying drawir.gs in which:-
F 5 ' ~s 2 sc~e~a~'c view o' ~ pe~-utc~.e~ls zccess
device acco~din~ to one embodimen~ o~ the
inventio~ ~laced subcutaneo~sly, an~,
Fi~ 2 is a view s~r.'l~ ~o Fi~re ; wi~h. the
perc-~;z~eous access ~evice p~aced percu~aneo~s'v.
F~s ~ is a photomicrograph c' c ^~ m_c-cn po~e s'~e
str~c~ure of Pn embodimen~ G~ the st-uc~ e
zec- b~ e inve-.~ic...
~'0 90/l~636 PCr/AI.9~/00'42
2Q333~6
_ ~ s ~ c ~. c ' r. ? r e ~ 2 ---c r _ - - 5 r~
-~ 7. i S;'~0W~ G p~~C`.~;cneO~'` access ~evice co7r,~~~s_n c
c~r.d~ 1 O o4 ar~rop-ia e cor~os- t~o:~ a~ e~ ;'^.. FG:
~e-~tone..; di21vs.6, 40r e..~mp' e, t~.e cathe ~e~ ~ s m~:~e 6, or
s :~.or~e 5 1 ~-one ~ 25 ~r, o~ rsi_e d~amete~ etwee~
a~o.~ 7 .n~ llimetres ~ The cc~ passes th-ou5h an.
ir.cisio.. :; .r. th~ s~ c th~ b~y ~ssue 1~ Ir. the
case o~ E)e. i ~or.ec;.L ci~lys s ~ ~ is der- i ~ed ~o ' ea~ hD oub~
O .~ ;a~e ~D- 2s io-~c ~s. poss~_1e_ f~ ~rr,~ OC~;s,
~r.cr.+~ or e~e.~ yea. s .
~ rO reme~ ~r. pla~e, the tube ~ C re~,u re~ ~G be ~eliG~'y
2~-h_-ec' wit~. r, ~he bo~ issue 1~ ~c~ ~his p~ ose z
'p'-_ _US C'_'4 ~ is 2~ .ache~' tc the pe. iphe-y o4 t.~e tube c;;
.Loc2~.~or~ mme_iately be_oh ~he s,.~ r. su~ ~ce. ~ no~-?orous
sieeve 15 w~ic~ r.~eS-,a:l ~ connec; e~7 O t.~e ~si~e
s~ ace 9~ ~he ~~o~s c~ s pe~-mzne.~'y co~.r.eete~ ~c .he
o~e.-s_rC ce o t~ be :~ b; ~c ~he s~e? o' ~'_ ..~ c~.
be pe--or~e~ c~ ;he ~ ~e c' mæ~.~f2ct~re c' tube ;0 o~ i. c2e.
w pe-.ormeA d~ he o?e~ra+io~. ~o ~nse-~ the tl~e ~ ir.tG
the ~o~y t~ssue 1~" The no?.-po~us sleeve 15 se~ves to
~solate the pGrOUS s~r~_tu-e cc the cu~ ;2 '-o~ t~e slue
Porous ma~e~~al from w~'ch the generally ~ylin~i-ica'
CU5' ~ is ~,ade ~s ~,iocompc;~ble ma~eric! const,~e~e~ by the
re~ia~lr.e'or~ ~r~cess so as .o ~cvi~e the blocompa;lble
ma+~er'a' with ~ ho~oçe~eous ~.terco~-.eeted porous ~ruc~ure.
~he p.ocess itseiC ~s ~esc-ibe~ c~ examp'e,
e-~ e ~?r~ c^~-o2-~ ?. z +_c;e bv Whi~e~ R.~ e~ ~:
. . ~ . .
W090/1~636 ~Cq~90/~02~2
2a3333~
en~le~ "Re~:a~. ne,o~r,: '. Ne~ ocese ~c~ P~epa~i~ Po.o-~s
Ce~2.~ . Me~z:, ~nr ~cly.m~ . ~~OS ~he. - ~z~e._zls".
~ he ~ec~ e is use~ fo. du~'ic~~ir.s the
microstr_^t-~re of carbcn2te s~eletc' com~or.er.~C ir. cerz~.ic,
met~' or ~G'yme- ~a;e~ials. ~he ~ocess 2:10ws ccr.trol of
pore size and the s~ze o' the l~te-connec ~ion between
ad~acent pores. ~he process is p2-ticu' 2~ se'u' whe~e
relat~vely ~lr.i~o~ p~re sl_e ~ pe--.ezb 1~ cc.~.e~
since c~-~o~ate skeletc st-_-.u es havir~ s~ac~.
cha~2cte-is-lcs z-e cc~.~.c~. ~ na~_-e.
Fo- pe-itonea' ~_clys~s, the heish~ (dl~.er.sio~ A ~n
F_5. 1) of .he gene.~ y c;' nc~~cz' c_~c ~trl-c~ e is i~ the
rzn~e Cf C.5 to 2 cer.time -es. Dimersion B i~ F's. : (the
thic~ness o~ the ~oro~s s'~uct~re o' the c~') is i-. the
~znge O.S mi:''metre to ~ r,~l'imet~es. ~hese d~mens on6 vary
accord~r.~ to the phyciczl size G' the patier.- or ar.i~l, the
~oy .oc~.ic~ o w~.^c~ e 'C ~s to be ~r~se~te~ ~n~
the pa-~_cula- tas~ which is ~o be per~o:me~ by the ~ube 10.
Fo- uses othe- thz~ pe~i~cnea' di~lysis, gener2~1y the
~imensior. P. wi' l be in the ra~gt 1 to S tin~es the outs~de
di~meter o~ the tubla7 element e:~c 1 osed ~y the c~;f.
Di~ensior~s generally ~^e sele~te~' c~ d~ to the pz. r.cu;z-
2p~ ic~tio:~.
~ :~ the su~cu.aneous a-~an~e~er.~ c Fi~ he c_ff 1~
is id~ally io~ated wi~h~ n ' centim.e ~, e o' t~.e sur.aco o~ the
ski:, 11. i.e. the to~ of the cu^f '2 a~ ~l'us~rate~' is wi;h_r.
ce-.timete o' the su~^Cc~e CL Ihe s~ ~r. :.
2~3333~
~''" 90~1S636 PCI/AU90/~0242
~`n6 i~.s~de diA~,ete- c.~ ti~e cu~ is selected to ~.c~c~.
the o~e~s'de d~ .r ~c- c~ I 'r.e tU~C '~'~.'s cl~r,er.s~c~
va--~ a-co~ ne t2s:~ w,._r;~ hc .'.~b~ C~ is ~c pe~ G.-r
he po-e s,-e withl~. the porou~s s- ~c ~ure of the cu. '
S ' ~ ~ wn~ -o~.ceA GCCC~di r,g ,0 tr.e , e~ic~ e'orm process, ~ s
rq~;tivel~J~ con~ nt, ucu~ . e se~r.c~ rio.C~ ur.
0~ of ~che ave-~5e p~re si~e c' the ~ ~r~:c ~ure .
Ave~G~e ;?o~e s ~ ze c~ e ~e'~ ec ' e~ e ~ .~r.ge
~C to ~OC Jr.ic~c~. . ~x~e-imer.t~' res.-' T.5 ~0 ea;e s-~g~est q5
10 ~o 3C~ ~.cror~.s c a p-~fer~ed -~o~^e si2s ranse C.orn ~;-~lch to
select w;~ ~s~ :C0 ~o .~2C r~ c~or.s _s the rn,os ~ c~esired .2n~e
from wr.lch ~o se~ect. hs ~.c'~ca~ec~ beloh~, the ~xper~me..~2'
. esults snow tha~ t~e ve~y smz' 1 pore s_-es do ~.ot ;llow good
flbrous tissue ;~ DW~. wh.ls' ve-y '~ se ~o-~ sizes ter.~ tc
p~od~_ce st_ue ~u. G charzc .e ~ s~_cs which ~~e mechan,cally not
des~ ~2bi~ .
~he pl~.ctoJ~.'crc ~rz~lz seow.n -.. ~ig. ~ is a sect.on
th-o~h c 2~0 r;. _~5~. po-e si7e c~ a~u~e ~.2de acco~ .s
to che repi~mine~ c~ m 5. ccecs '. o~ ,'ysyloxane . T~a~. cross
sec~l 3~. is ~ icz' o~ e~oss sec~_caC ~o ~e eY.~e_~ed irl the
po~o~s c~l~r str ~c~ e ;2 cf em~c~mer,~s c' the ..nve~.t~o:-.
The replzr''~e~or~. p:ocess ~reco~ ar..ly ~lows co-.tro!
over po~e s~ ze an~ 2c:e size conc' s cer~.c-~ a-.d ;?ore
~n~ercor.r~ec~1vl~ . conj~_-.c:ion w'~. t~.is ~:ima~y
2~ cha zcte~ ~ s: c, co,. -~o, is a,co exerteo ove- ~.e "~?oros ~ t~ "
~de~ine~' zc the ~ra-tio~. o ~ e b~; vol~:n.e o~ the ~.2~e~ c
occupie~ by voids ) c' the b~ocom~c~ ~ ~ e ma~e- ,a; ar.c', by
2~3333~
WO 90/l5636 PCr/AlJ90/002~2
~l~o~ a ~;.,de choice c. b,o~om.p2~ e ...a~e-~ci clss ~:lows
~:C'`,~,C; QVe~ the c~rr~.;?;iG~:e c~ the ~r.cte- G .
he e.~.~s~i~e-.~ cc -~. ~h,e j?c cs t~r sho~
g~ea~e- :;~a-. 20~ ~r._, idec;l~, sho~ e ~r. ~he ~Z~s~ 2~ ~c
~sO, Wh.e-e ~he pr~ oaC s~-_ctur~ c. tl~e c~a'~ is ~.ade fro~,
e~astome- c mzte~G:, ~he com~liance sno.~l ' be in the ra~g~
2; .o ~ S~o~e A po'nts az_ i~eally -. ti~ ge ~ to ~5
Sho~e ~ r~ rrc. ~h~ ~ t-~tc.~ 5~t ~ C ~ ber
p-evio~-s ~ es ibec a~ ._s--a ~e~ -S . - hac 2
C~.. P_~G~e O' a~?ro~ r.G~e'~ s".o e ~ E~C ~.~s a.. - a po,~s
O f arou~.ct. 30~,
r ~ ~, . , c' srloses ~ secorld emb~ e~.~ c; ';~e ~ e..~ i or.
where };e p~s have ~ ~.e szme nu:~be~s ~s ~rl Fi~ Th~
str_c~ a;~ ts compos't~c~. s _~. c:` -espects t~.~ same as
that desc. 1 bed wi ~h respGc~ ~o Fi~ . ', SGtre t~a . ~he c
's ~'aceo' pe~ .ar,eous,y so +h~ ~..cies e few
.e-~es z.bov e the s~,.~'ace o' trle S\ i1~. 12y~5 ~ . The
e~:pe~i~er.~r: -es._'~s ~o be desc._~e~ ~e_ow r.-icc~e ~hc.. ~hi5
p'zcemer.; o' ~ha cl; ' is r~ot as p~efe-re~ Z5 ~he 2~range...er.
o- ~ 5 .
Res.~l~s ~^ dzte ir.~'~cate t~z. t~e s~r~c~ure o' +he
~irs' embo~i~en~ describ~d w't~. re~rer~oe ~o Fis. . zllows
use o~ the s~ple, ge~erc.l'y cyli~.d~icl cu C str_cture
hzvir.~ isr.ztely th~ same di~e~.s ' or.s z.s the c ~- er.~ly
pre.er~e_ Da--o~ e c... -fs use~ ~or zr.c~o-ing p~ poses.
~iowever the pa~ ticulzr struc~ure desor,be ~ here a' lows ~he
possl~ y o~ placi~ the ~ eve~. ciose~ ~e tne s,~
WO 90/1 j636 Pcr/Al-lg~/~o~4~ 3 3 6
s` ~caCG ~2^~ ' 5 des_. ab' e w~ .e ~a~ . c:C ' s ~-~c ~_. ec
t~e~ebv m2~ ., st:- ~cz~ i-.s~ o.. G2s~er ~ lesse~r.
--2'C.~ . ~ ~ ` O~`.Z ~ tne s ~~uc ~rs show= ~ron~i ~2 o .
~irovld'n~ 2-`. i.~proveG sec' a~2ins~ the o~s de enJ~-~r~.e~-
c~ce _-.g-ow~h o~ ~o~y ce' ls int~ ~e porous ~ c~ e has
tar~e~ C12Ce~ oveY a s ~ x wee'r~ or so pe-ic,~ .
SY.a.. ~`' e
Su~ c .~ . ~r. e ~ c ' ~, r ~ 5 '; " ~ d _ s c c ~ e - c _ 1 8 ~ _ . . . a
c~ove ~he s. ?e-~ic,a' fascic ~G S ~.UC.~' t~ mpo-t2nce o~ eo-
~s~ _c~ e z~c. ro:e s~e? c-. ~.SS';E ~~cs~;~`a.
The ~r~ z' samr~le ct:'' s~~~c ~:-es we-e made ~'rc.
_one r_~be-, so~ a~.e an~ hycrcxyzpc~te usir.~ .3ae
~ es~!2~ .e'o~. p-ocess so ~s te p-o~_ce s2s!~.r~e s~r~_c~-es
;~av~:~5 res~ective'~ ~r ~._C~C.. ~ve-ase po~e C';7~, lC~ c o~,
2~e~2se pc~^ s_-e, 2C'' ~.~ c~o-. 2ve~c~ ?ore s-'-e a~ 50C
--. --ro.. ~ve~aSe po~e s ~e .
'rhe ^C .,. ~o-. ?or~ 5_2~ Ea~ es ~ eGC'~: C~
r_:e-- z;s showe- ' ~ ~ t e , ~ ~-o~_s : ~ S5~.16 _;`,'--Oh--~ i"...C
pc-es z~te- fo~_r weel;~ _~r.r~ ' or. . ~ . a~?ecred ~ho ~ the
pore size wzs si~p'y too s~ o ~r- 6 ~fe--ive .
~ hc 100 ~r.ic-o~ s ~ c~u-es pe~f~rme~ well glvir~g ~a~ure
c^;~ge-. arl~ 50O~ lng~owth 24te~ _o~r wee~s wlt~. the ~,a~c: ty
c' ?ose ';'le~. ~ e '~.y~roY.yapa~~e ca-:se~ ~hr leas~
; .~,amm~tio:~ w~. 1st ~lyure-~ar~.~ c2use~ t:~Le ~.os:.
Th~ 200 ~ o. on sa~.~les pes~-med ;r.c,r ~. ~he sa~e zs ~;~r-
loo ric-on ~ les b_~ w~ c,_a'~5~ c~ ow~. be_~~.~ c
be ~t~ a-.~ t:~e ~r~.s~n ~ ...' lamJr,~-~ c-. be ~.5 - ~~ie
2~333~
W090/l~636 PCT/AU90tO~242
less. ~h~se s~,ples ,,, ~c~cet~ t~.e o~ u~. resul .5 .
O~.ly hy-~c~y2?2t~e sam~ies wer~ made wi~ CC ricro~.
~o-e Q~ze. ~e ,es_;~s Oc t~.~s s~~u~u~e wer~ ~e~e-~'`y t:~e
same as ~or the ;OO zn~ ~OO ~.'e-on pore s'ze ~y~roxya~atite
sarples. P.oweve-, hyc.. oxyap2-ite i5 b~Oac~i~e anG d.ssclves
~ the t~csles ove~ .ime. ~he 500 ~_c-on hy~o~y2pzl'~e
s~p~e s~o~e~ a greater p-edelicticr ~o th~s benaviou- tha.
the s~,~lle ~^~e ~e h~,~c'~c~ya"atite s~,..rl~s.
. ~ener_ ~y ' l_~or. .ubbe- W2S four.~ to ~ave bet~e-
- lO ir.~iar,r.e~ic-. beha~o~ hcn poly~-e~a2~e. ~y~-oxy2p2t' ~e
~-oba 1~ pe:~o-me~ t~.e bes~ ~s ~c- as ~~~lam~2~ior. ~es~lts
are conee-nec ~u. is a~ .here~tly brittle materi21 w~c~
L~ CI~ hav~ the des~r~le co~ ee ehzrecte~-s~
s ~ lcone rub~er or ~oiy~-e-hz~e.
~xa~.~le 2
_s were a;co e-~ cte~ us~r.~ s.~ee,". ~.e c~eC~s ~se-
~r.-luded an ~nteçr~' ~o~o~ ~'an.ce ~zd~ ~ro.~ the sa~.e
t.~e res~ c' ~r.e poro~s s~,~c~ure c~ ~he C~ ' and
eV.~e..- -.~ 2~r_ 0:;' ..-2 ~el~ .'l'imetres ~a~ al!y awzy ~.~r. ~~.e
2C _~' cy''.c-~ca' su-face. 5he ~ 6es we-e ~nco-pora~ed
- ~ere'y 2s 2 ~u~s-~tu~e fo- the s~ 'is~ng effec: r.o~r,a ly
~-ov~e~ by the tube 1~ to ~lch the c~f 1~ is attac~.ed i-,
n~ ' usa~. C~ s:~uc~ures c Dow Co r.~n~ Q~-48~0
s~l'cone r~be. an~ ~o'yurethan~, ~ot~. o~ lC0 ~.crcn ~ve.a_e
pcre size ~n~ 200 ~icsor. ave:age pore size we-e ~ade
acc~-c~r.g ~o ~he se?la_.ir.e'or~. p. ocess an_ ins .~' ie~ ~th
~ o~tæ~eous~y zn- p~r~u.æ~eo~zsly ~n ~hee~. Th.e CU5~
WO 90~1;636 PCr/AI,'~O/OO~ 3 ~ 3 3
S ~ tU~ es ~"e~e f !c-~g~r' ~s ~ . t~ e~' o~C z~ ' e~ hc
~eascns 5' ve~ h ~-e- ~ ol~s exz:r.?les . he "~ ess -' ~h~
i~rla~ ~C O~!er G ~welve wee-: z,.~ ~wer.;~ 5 ~:~ wee!; ~,e-ioc waC
obs e ~vec .
- U' ~imately ~he~ a2peare~ to be ~ ~ ~~ . c- 'fe~e~ce ir.
ep~er~c~ ~ehav_o.- be~wee:~ the ;OG ~icrc.. ~:~d the 202 r~c-or~.
pore s~ze ~ zn~s . T-s-owth t~ ssue wcs se~erai~y s ~ ' e
ha~ing ~ib-o~'~ a~;s a;.~ ' o~ 1 eve:s c ' .,..~-.._c ,..~ am:rcr^r~
ce 1 s . Tiss~e vas. ~la~~ sa' ~ o~ was ar~var.~e~ w~ ~h~ e ;?~ es
lC ~S~ rwe' ve weC.;c . ?e: - -_r..~ ~ .'lam,r~ Ar;' -es~onse W2~
w~ th ~o~e 'occl c~ ~ ;ec ~ o.:s C4 ly~hoc-~tes . Su}~c~ltaneous
c~ ' placeme-.~ a::ower 'o~~m.a~_or. o. a r~c~ e sta~le '~ssue
~nterface a- rhe e~ ~ cite than per_~; ane~uc c~ placerr.en~ .
g~E~ .
. C~ C..-.~CG o r~ . 25 ~ene-~lly i` l:srrc-ted arld
des~_ bed ~ espe~r c~ F_Ç. 1 O- F~ hæv~ns 2 ~
~,c-ous ~ .,ru-r- c5 i; ~u¢--a~ed _n sec~_c~ J n ~; 5 3 was
pre~c -e~ o... Dow Sor~.'r., Q1-~,8~0 s~ ieo~.e ru~ber poro~s
mate-..a: made us~ t:~e re?lar:~e~c-:: process. q'he
~ep'am,neforr, process w2s ca~rie~ c ~t SG 25 to p oduce 2 c'__C
3~avi~ o:slo~eneous . ir. Lercorn~cte~ pO~OU5 s ~ c~u-e ~vin
2 csmpli~nce of approx.m2te'Y ~ Shore A po~s, a ~oros_ty
o' z~proi:imately 30% an~ - pore Size o" app. oxi~ately ~00
~.icrome~e. s .
V2-ious ~4~;'icæ~...c-~.5 ~r.ay be ~ade i:l cetc'is oS esis.;
a~.~ co~.s~ruc~ i or. w:...'~o_~ de?a-t_r.s ~-o~. trle SC0~9 æn' 2r~
^~ t~.e i:~ve-. ~ ~ or. .
