CA2642723C - Medical balloons and methods of making the same - Google Patents
Medical balloons and methods of making the same Download PDFInfo
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- CA2642723C CA2642723C CA2642723A CA2642723A CA2642723C CA 2642723 C CA2642723 C CA 2642723C CA 2642723 A CA2642723 A CA 2642723A CA 2642723 A CA2642723 A CA 2642723A CA 2642723 C CA2642723 C CA 2642723C
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- Prior art keywords
- balloon
- base polymer
- region
- polymer material
- carbonized
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/082—Inorganic materials
- A61L31/084—Carbon; Graphite
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/28—Materials for coating prostheses
- A61L27/30—Inorganic materials
- A61L27/303—Carbon
Abstract
Medical balloons are provided that have enhanced properties, such as enhanced puncture and scratch resistance.
Description
_MEDICAL BALLOONS AND METHODS _OF MA.K1NQ THE:
SAME
TECH NfCAL FIELD
This diselosure, relate.4 ka= medical balloons, Wid to methods of making. the BAC:KGROUND
The body includes varioits passageways :such as :arteries, other blood vessels, and other body lumens: These passageways semetiines: beef:nue occluded, e.g., by a tinuor orrestrieted by plague. To widen im occluded body vessel, balloon catheters in pan be used, e,g.,a angioplasty A balloon catheter MI include an inflatable and deflatable balloon carried by a long :and narrow catheter body. The balloon is initially folded around the catheter body to reduce the. radial profile of the balloon catheter for easy insertion into tile body.
Wring use, the Nded balloon can be delivered to a target keation in the vessel, e.g.õ a portion occluded by plaque, by threading the balloon Catheter over guide wire emplaCed in thti:Ves*., The balloon is then inflated, e..gõ by introducing a fluid WO the interior ofthe:balloon. Inflating the balloon can radially expand the vessel so that the vessel can pentiit an increased Tatt ofbkvd flow. After use, the balloon i8 deflated :and withdraWn fren the body.
In another technique, the :balloon catheter can also be used to position a medical device; such as a stent or a stent,graft, topen wilor to reinforce:a blocked passageway. For exanipie, the gent Can be delivered inside the body by a balloon catheter that supports :the stent in a conipacted or reduced-sic fonn as. the stent is transportt4 to the :target site: Upon re:401141,g the site, the balloon cap be inflated to defonn and to fix the expanded stent at a predetermined position in contact with the Ininen wat. Thc balloon can then be deflated and the catheter withdrawn. Stent delivery is further discusscd in Heath; US.:6.:29%7Z1., the entire disclosure of which is beithY indorPerated by reference herein.
One common balloon catheter design includes a coaxial arrangement of an inner tube surrounded by an outer tube. The inner tube typically includes a lumen that can be used for delivering the device over a guide wire. Inflation fluid passes between the inner and outer tubes. An example of this design is described in Arney, U.S.
5,047,045.
In another common design, the catheter includes a body defining a guide wire lumen and an inflation lumen arranged side-by-side. Examples of this arrangement are described in Wang, U.S. 5,195,969.
SUMMARY
In one aspect, the disclosure features a medical balloon that includes a balloon wall having a base polymer system with an integral modified region including carbonized base polymer material.
In another aspect, the disclosure features a balloon catheter that includes a balloon wall having a base polymer system with an integral modified region including a carbonized base polymer material.
In another aspect, the disclosure features a method of making a medical balloon that, includes providing a polymer system; treating the polymer system by plasma immersion ion implantation; and utilizing the treated polymer system in a medical balloon.
In another aspect, the disclosure features a method of making a medical balloon that includes providing a polymer system; treating the polymer system by ion implantation to modify the polymer system without substantial deposition of non-polymer system material; and utilizing the treated system in a medical balloon.
In another aspect, the disclosure features a medical balloon formed by any of the above described methods.
In another aspect, the disclosure features a medical device that includes a base polymer system including coextruded polymers, the base polymer system having an integral modified region of carbonized base polymer system material.
SAME
TECH NfCAL FIELD
This diselosure, relate.4 ka= medical balloons, Wid to methods of making. the BAC:KGROUND
The body includes varioits passageways :such as :arteries, other blood vessels, and other body lumens: These passageways semetiines: beef:nue occluded, e.g., by a tinuor orrestrieted by plague. To widen im occluded body vessel, balloon catheters in pan be used, e,g.,a angioplasty A balloon catheter MI include an inflatable and deflatable balloon carried by a long :and narrow catheter body. The balloon is initially folded around the catheter body to reduce the. radial profile of the balloon catheter for easy insertion into tile body.
Wring use, the Nded balloon can be delivered to a target keation in the vessel, e.g.õ a portion occluded by plaque, by threading the balloon Catheter over guide wire emplaCed in thti:Ves*., The balloon is then inflated, e..gõ by introducing a fluid WO the interior ofthe:balloon. Inflating the balloon can radially expand the vessel so that the vessel can pentiit an increased Tatt ofbkvd flow. After use, the balloon i8 deflated :and withdraWn fren the body.
In another technique, the :balloon catheter can also be used to position a medical device; such as a stent or a stent,graft, topen wilor to reinforce:a blocked passageway. For exanipie, the gent Can be delivered inside the body by a balloon catheter that supports :the stent in a conipacted or reduced-sic fonn as. the stent is transportt4 to the :target site: Upon re:401141,g the site, the balloon cap be inflated to defonn and to fix the expanded stent at a predetermined position in contact with the Ininen wat. Thc balloon can then be deflated and the catheter withdrawn. Stent delivery is further discusscd in Heath; US.:6.:29%7Z1., the entire disclosure of which is beithY indorPerated by reference herein.
One common balloon catheter design includes a coaxial arrangement of an inner tube surrounded by an outer tube. The inner tube typically includes a lumen that can be used for delivering the device over a guide wire. Inflation fluid passes between the inner and outer tubes. An example of this design is described in Arney, U.S.
5,047,045.
In another common design, the catheter includes a body defining a guide wire lumen and an inflation lumen arranged side-by-side. Examples of this arrangement are described in Wang, U.S. 5,195,969.
SUMMARY
In one aspect, the disclosure features a medical balloon that includes a balloon wall having a base polymer system with an integral modified region including carbonized base polymer material.
In another aspect, the disclosure features a balloon catheter that includes a balloon wall having a base polymer system with an integral modified region including a carbonized base polymer material.
In another aspect, the disclosure features a method of making a medical balloon that, includes providing a polymer system; treating the polymer system by plasma immersion ion implantation; and utilizing the treated polymer system in a medical balloon.
In another aspect, the disclosure features a method of making a medical balloon that includes providing a polymer system; treating the polymer system by ion implantation to modify the polymer system without substantial deposition of non-polymer system material; and utilizing the treated system in a medical balloon.
In another aspect, the disclosure features a medical balloon formed by any of the above described methods.
In another aspect, the disclosure features a medical device that includes a base polymer system including coextruded polymers, the base polymer system having an integral modified region of carbonized base polymer system material.
2 In another aspect, the disclosure features medical ballooliS Whirl exhibit a D
peak andior a Ci pm& in Raman.
Other aspects or embodiments may include combinations of the features in the aspects above and/or one or more: of the following. The carbonized region includes diamond-like material and/or the carbonized region includes graphitic m.aterial. The modified region includes a region of crosslinked base polymer material. The crosslinked region is directly 'bonded to the carbonized base polymer material and to substantially unmodified base polymer material. The medical balloon can include a region of oxidized base polymer material, the oxidized region being directly bonded to the carbonized material without further bonding to the base polymer system.
The modified region extends front an exposed surface of the base polymer system.
The moduhis of elasticity of the base polymer system is within about il-10% of the base polymer system without the modified. region. The thickness of the modified region is-a.bout 10 to about 200 rim. The modified region is about 1% or less of the overall thickness of th.e base polymer system. A hardness coefficient of the carbonized base polymer material is about 500 Vickers liardnms (kemin2) or more. The ballocm has a fractured surface maiphology having a surface fracture density of about five percent or more. The base polymer system carries a therapeutic agent. The base polymer system .includes coextruded polymer layers. A compliancy of the balloon is less than percent of an initial diameter of the balloon between an internal pressure from about 2 bar to about 15 bar. The balloon catheter is sized for .use in the vascular system. The balloon catheter is sized for use in. the coronary arteries. The balloon catheter includes a stent positioned over the balloon. The ion energy and dose is -controlled to form a carbonized region in the polymer system. The ion energy in a.
range of about 15 keV or more and a dose of about I X1.015 ions/en-12 or more.
A
stent is about the medical balloon. The treating of the polymer system utilizes an ion selmted from the group consisting of hydrogen, "helium, boron, neon, carbon, oxygen, nitrogen, argon, or mixtures of these. The modified region includes an interfitce of coextruded polymers.
peak andior a Ci pm& in Raman.
Other aspects or embodiments may include combinations of the features in the aspects above and/or one or more: of the following. The carbonized region includes diamond-like material and/or the carbonized region includes graphitic m.aterial. The modified region includes a region of crosslinked base polymer material. The crosslinked region is directly 'bonded to the carbonized base polymer material and to substantially unmodified base polymer material. The medical balloon can include a region of oxidized base polymer material, the oxidized region being directly bonded to the carbonized material without further bonding to the base polymer system.
The modified region extends front an exposed surface of the base polymer system.
The moduhis of elasticity of the base polymer system is within about il-10% of the base polymer system without the modified. region. The thickness of the modified region is-a.bout 10 to about 200 rim. The modified region is about 1% or less of the overall thickness of th.e base polymer system. A hardness coefficient of the carbonized base polymer material is about 500 Vickers liardnms (kemin2) or more. The ballocm has a fractured surface maiphology having a surface fracture density of about five percent or more. The base polymer system carries a therapeutic agent. The base polymer system .includes coextruded polymer layers. A compliancy of the balloon is less than percent of an initial diameter of the balloon between an internal pressure from about 2 bar to about 15 bar. The balloon catheter is sized for .use in the vascular system. The balloon catheter is sized for use in. the coronary arteries. The balloon catheter includes a stent positioned over the balloon. The ion energy and dose is -controlled to form a carbonized region in the polymer system. The ion energy in a.
range of about 15 keV or more and a dose of about I X1.015 ions/en-12 or more.
A
stent is about the medical balloon. The treating of the polymer system utilizes an ion selmted from the group consisting of hydrogen, "helium, boron, neon, carbon, oxygen, nitrogen, argon, or mixtures of these. The modified region includes an interfitce of coextruded polymers.
3 EiTibodinnt.tits may have one:or more.of the following:advantages; A balloon is provided in which properties, such as puncture reSistailee, seiatehresistance, flexibility;.butSt Strength; and drug release...:are.enhariced fiir a:.given application. In particular,: stent.da.vesty balloon s provided with .a hg .scratch resistance.
The.
SCratCh rtSjstancevftho..bailotni is enhaneedlyproviding.a. balloon wall that incittOei a itlatively hard re0on, 04õ including a diamptid-like material (e.gõ diamond like eaition.or arnorpliolis diamon4 which Is.fightly adhered to a base. polynier sy-stein.
.forthetfeatutes, embodithentS, and adVantages. Wow:
DESCRIPTION OF DRAWINGS
it) 'FIGS. I A. IC are partial longitudinal .cross-sectional .views, illustrating delivery 07.n:sten:thin collapsed state expansion tif the :stmt.:, and .deplo yment of the stein: in a. bodyltimen., FIG :2A is a transverse end. on prosssectional. view-through a Wan of n halloon,..showing an unmodified ba,se polymer systentregion.and. hard base.polymer modified region, :FIG:2B is a schematic...illustration of the compositional makeup:of a portion of the :balloon. wall astratod in Fla A.
Fix 3A is A.sithelitilti: eroSs-seetional. ''''''''''' of n plasma inunerSion ion implantittion:("Pla") apparatus..
2o Fig, 3:ffis a .sehematic top view of ten ballooria ih a.sampleholder (metal god etrxt íy ternoyed front View), FIG 3:e is a detailed cross-sectional view. of the plasma immersionion..
implantation apparatuS. of FIG A.
4A is .n.1011gAti4imil crosssectional vi ncoexinided balloon, illustrating the ballepn A.,vall prior to modification.
FIG, 4g iS.n longitudinal crosseetional vie of thecoettuded balloon of 4A, illustrating hallopn wall after .modification.
FIG 5A is .aphototnicrograph a balk= surface prior to modification...
FIG 513 iS..a photornierograph .of a balloon Surface After modification.
The.
SCratCh rtSjstancevftho..bailotni is enhaneedlyproviding.a. balloon wall that incittOei a itlatively hard re0on, 04õ including a diamptid-like material (e.gõ diamond like eaition.or arnorpliolis diamon4 which Is.fightly adhered to a base. polynier sy-stein.
.forthetfeatutes, embodithentS, and adVantages. Wow:
DESCRIPTION OF DRAWINGS
it) 'FIGS. I A. IC are partial longitudinal .cross-sectional .views, illustrating delivery 07.n:sten:thin collapsed state expansion tif the :stmt.:, and .deplo yment of the stein: in a. bodyltimen., FIG :2A is a transverse end. on prosssectional. view-through a Wan of n halloon,..showing an unmodified ba,se polymer systentregion.and. hard base.polymer modified region, :FIG:2B is a schematic...illustration of the compositional makeup:of a portion of the :balloon. wall astratod in Fla A.
Fix 3A is A.sithelitilti: eroSs-seetional. ''''''''''' of n plasma inunerSion ion implantittion:("Pla") apparatus..
2o Fig, 3:ffis a .sehematic top view of ten ballooria ih a.sampleholder (metal god etrxt íy ternoyed front View), FIG 3:e is a detailed cross-sectional view. of the plasma immersionion..
implantation apparatuS. of FIG A.
4A is .n.1011gAti4imil crosssectional vi ncoexinided balloon, illustrating the ballepn A.,vall prior to modification.
FIG, 4g iS.n longitudinal crosseetional vie of thecoettuded balloon of 4A, illustrating hallopn wall after .modification.
FIG 5A is .aphototnicrograph a balk= surface prior to modification...
FIG 513 iS..a photornierograph .of a balloon Surface After modification.
4 FIG. 5C is a schematic top vie.w ()f a balloon surface atter modification, showing fissures and "islands" that are defined by the fissures.
FIG 6 is a. seties of FTIR MR spectra of fAX 7033, films taken from 1850 cin to 900 cm-1 atter P111 treatment at 30 keV., the bottont spectrwn.
being the untreatmi film, the other spectra being films treated respectively with 5 X
1014, 1015, 5 X 1015, 1016, 5 X 1016 and= 1017 ions:jet=-n.2, FIG, 7 ìsa series of FTIRAF1. spectra of PE.BAX41. 7033 films taken livrn 3700 cm-1 to 2550 cm-1 after Pill treatment at 30 keV, the bottom spectrum being the untreated film, the Other spectra being fihris treated respectively with 5 X
1014, 101', 5 X 101', X 101'6 and 1011 ionsicm2.
8 is a series of Raman spectra of PE.BAX. 7033 films taken from 1900 cm.1 to 7'75 enfi itfita7 Pill treatment at 20 keV, the bottom spectrum being the untreated film, the other spectra being is treated respectively with 5 X 1014, 10'5, 5 X 101', 1.0'6 and 5 X 1016 ions/cull.
Pia 9 is a series of Raman spectra of 1)EBAX41' 7033 films tak.en from 1900 .1 to 775 cm-1 atter P111 treatment at 30 keV; the bottom spectrurn being the untreated film, the other spectra being films treated respectively with 5 X
1014, 1015, 5 =X 1015, le, 5 X 1016 and 1017 ionslcm2.
FIG 10A is a series of 1.IV-Vis transmission Spectra of PEBAX 7033 films take from 500 ran to 240 nrn after Pril treatment at 20 keV; the bottom spectrum being the untreated fihn, the other spectra being films t.reated respectively with 5 X
1014, 10's, 5 X 1015, 10'6, 5 X 10'6 and 1017 ionslcm2.
FIG, 1 013, is a series auv-vis transmission spectra of PEBAKQ 7033 films taken from 500 nm to 240 TIT11 after PIII treatment at 30 keV, the bottom spectrum being the untreated film, the other spectra being films treated respectively with 5 X
1014, 1015, 5 X 1015, 1016,5 :x 101' and 1017 ionsicm2, FIG. 11A shovvs optical density of PEBAX 7033 films at 250 nm as a function P111 dose at 20 keV and 30 keV, FIa 11B shows optical density of1)F.BAX = 7033 films at 55 as as a fillietion P[ii dose at 20 keV and 30 keV:
FIG 6 is a. seties of FTIR MR spectra of fAX 7033, films taken from 1850 cin to 900 cm-1 atter P111 treatment at 30 keV., the bottont spectrwn.
being the untreatmi film, the other spectra being films treated respectively with 5 X
1014, 1015, 5 X 1015, 1016, 5 X 1016 and= 1017 ions:jet=-n.2, FIG, 7 ìsa series of FTIRAF1. spectra of PE.BAX41. 7033 films taken livrn 3700 cm-1 to 2550 cm-1 after Pill treatment at 30 keV, the bottom spectrum being the untreated film, the Other spectra being fihris treated respectively with 5 X
1014, 101', 5 X 101', X 101'6 and 1011 ionsicm2.
8 is a series of Raman spectra of PE.BAX. 7033 films taken from 1900 cm.1 to 7'75 enfi itfita7 Pill treatment at 20 keV, the bottom spectrum being the untreated film, the other spectra being is treated respectively with 5 X 1014, 10'5, 5 X 101', 1.0'6 and 5 X 1016 ions/cull.
Pia 9 is a series of Raman spectra of 1)EBAX41' 7033 films tak.en from 1900 .1 to 775 cm-1 atter P111 treatment at 30 keV; the bottom spectrurn being the untreated film, the other spectra being films treated respectively with 5 X
1014, 1015, 5 =X 1015, le, 5 X 1016 and 1017 ionslcm2.
FIG 10A is a series of 1.IV-Vis transmission Spectra of PEBAX 7033 films take from 500 ran to 240 nrn after Pril treatment at 20 keV; the bottom spectrum being the untreated fihn, the other spectra being films t.reated respectively with 5 X
1014, 10's, 5 X 1015, 10'6, 5 X 10'6 and 1017 ionslcm2.
FIG, 1 013, is a series auv-vis transmission spectra of PEBAKQ 7033 films taken from 500 nm to 240 TIT11 after PIII treatment at 30 keV, the bottom spectrum being the untreated film, the other spectra being films treated respectively with 5 X
1014, 1015, 5 X 1015, 1016,5 :x 101' and 1017 ionsicm2, FIG. 11A shovvs optical density of PEBAX 7033 films at 250 nm as a function P111 dose at 20 keV and 30 keV, FIa 11B shows optical density of1)F.BAX = 7033 films at 55 as as a fillietion P[ii dose at 20 keV and 30 keV:
5 Flci. :12. shows optical density Pflow-deosity.polyethytene, .(LDPE). films.at 250 mu as a function PM..dOse at..5=:keV, 10 keV., 20.keV arid30 keV.
ìS aphOtOtnicrograph a PE B AIX, 7033 balloon. surface after treatment with le ísfn2 at .30 keV
ìS aphOtOtnicrograph a PE B AIX, 7033 balloon. surface after treatment with le ísfn2 at .30 keV
6 FIG. .14. shows .stresS-stain curVosiOr Sevetal P.EBAX 7033 films treated. ..with P111, Fla 15 sows :strength ot'PEBAX4 7033 filinsAreated=With NE 46 a &action of dose at '20 '<eV and 30keV:
FIG 16 slU)ws.pereent. elongation at brealc. of PEBAX!' 7033 films.as l'uriction. of dose. at 20 keVand 30 kW.
FIG. 1.7 shows.imOdtilus Of elasticity of PEB.A.X* 7033 Mills as a fupetioriof dose at '20 keV. and 30 keV.
FIG. 1 8 shows:serateb testin&GIPIEBAX* 7033 plates at a variety a doWsat 20 UV (dose in box is. expressed in multiples el015 .FIG.1..4.shows.scratctitesting of PEBAXs 7033 ..06:tes at a .variety of doses at.
30 keV ((lbsein.boxis-expressedin Intiltiples of 1015 ions/CIO.
'MG 20 shoWs.:hardneSS coefficient of.PERAXs .7033 plates as. a function .of dose at 20 4110.30 .keV.
.FIG .21 shows load ..curves 'obtained tising atothiCforee microscopy (AF M)tr 20 a bard Silicon plate Oa refel'ence) and an. untroa* PV,BAX1') 7033 plate.
FIG. 22 shows .load.curves.ob.tained. using AF M for a PEBAXs 7033 plate treated with.PHI. at a dme.of 1.01*4' ions/cm:2' and 30 .keV.
FIG,23 .shows.loadeurves.obtained using AF M: Ibr a PEBAXs 7033 plate -1,eated with PHI at Cif= Of 1015. ìcinsfcrri2 and 30 keV
2.5 IFIG 24 :Shows loadcurves 'obtained usingAFM for a PEBAX, 7033 plate treated :krith 1IT1 at a dose of 5 X 10" ions.e.'en? and FIG 25 .shows apparent hardness toefEcient a .first part of a loadourve .(module it and al seeond..part ofa load curve (thOdule forP:f.3BAX,' 7033 pla.tes.
=tteated at. yarious doses at 10 keV.
3.0 Fla 26: shows mo.dults cif dastkityof PE3AXt'7033. funetion.of (Jost,- at 10 keV, 20 keV and 30. lieV.
FIG 27 shows a normalized dose distribution as a function of balloon angle.
FIG 28 shows a dose distribution for a Plil apparatus having an additional.
electrode.
FIG. 29 is the dose distribution of FIG. 28 in an X-Y plane.
DETAILED DESCRIPTION
Referring to FIGS. 1A-1C, stern 10 is placed over a balloon 12 carried near a distal end of a catheter 14, and is directed through a lumen 16, e.g., a blood vessel such as the wronary artery,- until the portion carrying the balloon and stent reaches the region of an occlusion 18 (FIG IA). The stent 10 is then radially expanded by o inflating the balloon 12, and is pressed against the vessel wall with.
the result that occlusion 18 is compressed, and the vessel wall surrounding it undergoes a radial expansion (FI(ì 1E4). The pressure is then released from the balloon and the catheter is withdrawn from the vessel (FIG 1C).
Referring to FIG 2A., balloon wall 20 having overall thickness TI includes an outer surface 22 exposed to the stent and an inner surface 29 exposed to inflation fluid in the balloon interim The balloon wall is formed of a base polymer system including an unmodified region 2( and a hard, modified region 28 of thickness Tm.
The unmodified base polymer has a thickness TB that is the difference between the overall wall thickness Tw and thickness Tm of the modified region.
Referring to FIG. 213, the modified region has a series of sub-regions, including an oxidized region 30 (e.g., having carbonyl groups, aldehyde groups, carboxylic acid groups and/or alcohol groups), a -carbonized. region 32 (e.g., having increased sp2'bonding, particularly aromatic carbon-carbon bonds and/or sp3 diamond-like carbon-carbon bonds), and a crosMinked region :44. In particular embodiments, the crosalinked region 34 is a region of increased polymer crosslinking that is bonded directly to th.e unmodified base polymer system and to the carbonized region 32. The carbonized region 32 is a band that typically includes- a high-level of sp -hybridized carbon atoms, e.g., greater than .25 percent sp3, greater than 40 percent., or CVOI1 greater than 50 percent sp3-hyridized carbon atoms, such as exists in ao diamond-like carbon (DI,C). The oxidized region 30 that is txynded to the carbonized
FIG 16 slU)ws.pereent. elongation at brealc. of PEBAX!' 7033 films.as l'uriction. of dose. at 20 keVand 30 kW.
FIG. 1.7 shows.imOdtilus Of elasticity of PEB.A.X* 7033 Mills as a fupetioriof dose at '20 keV. and 30 keV.
FIG. 1 8 shows:serateb testin&GIPIEBAX* 7033 plates at a variety a doWsat 20 UV (dose in box is. expressed in multiples el015 .FIG.1..4.shows.scratctitesting of PEBAXs 7033 ..06:tes at a .variety of doses at.
30 keV ((lbsein.boxis-expressedin Intiltiples of 1015 ions/CIO.
'MG 20 shoWs.:hardneSS coefficient of.PERAXs .7033 plates as. a function .of dose at 20 4110.30 .keV.
.FIG .21 shows load ..curves 'obtained tising atothiCforee microscopy (AF M)tr 20 a bard Silicon plate Oa refel'ence) and an. untroa* PV,BAX1') 7033 plate.
FIG. 22 shows .load.curves.ob.tained. using AF M for a PEBAXs 7033 plate treated with.PHI. at a dme.of 1.01*4' ions/cm:2' and 30 .keV.
FIG,23 .shows.loadeurves.obtained using AF M: Ibr a PEBAXs 7033 plate -1,eated with PHI at Cif= Of 1015. ìcinsfcrri2 and 30 keV
2.5 IFIG 24 :Shows loadcurves 'obtained usingAFM for a PEBAX, 7033 plate treated :krith 1IT1 at a dose of 5 X 10" ions.e.'en? and FIG 25 .shows apparent hardness toefEcient a .first part of a loadourve .(module it and al seeond..part ofa load curve (thOdule forP:f.3BAX,' 7033 pla.tes.
=tteated at. yarious doses at 10 keV.
3.0 Fla 26: shows mo.dults cif dastkityof PE3AXt'7033. funetion.of (Jost,- at 10 keV, 20 keV and 30. lieV.
FIG 27 shows a normalized dose distribution as a function of balloon angle.
FIG 28 shows a dose distribution for a Plil apparatus having an additional.
electrode.
FIG. 29 is the dose distribution of FIG. 28 in an X-Y plane.
DETAILED DESCRIPTION
Referring to FIGS. 1A-1C, stern 10 is placed over a balloon 12 carried near a distal end of a catheter 14, and is directed through a lumen 16, e.g., a blood vessel such as the wronary artery,- until the portion carrying the balloon and stent reaches the region of an occlusion 18 (FIG IA). The stent 10 is then radially expanded by o inflating the balloon 12, and is pressed against the vessel wall with.
the result that occlusion 18 is compressed, and the vessel wall surrounding it undergoes a radial expansion (FI(ì 1E4). The pressure is then released from the balloon and the catheter is withdrawn from the vessel (FIG 1C).
Referring to FIG 2A., balloon wall 20 having overall thickness TI includes an outer surface 22 exposed to the stent and an inner surface 29 exposed to inflation fluid in the balloon interim The balloon wall is formed of a base polymer system including an unmodified region 2( and a hard, modified region 28 of thickness Tm.
The unmodified base polymer has a thickness TB that is the difference between the overall wall thickness Tw and thickness Tm of the modified region.
Referring to FIG. 213, the modified region has a series of sub-regions, including an oxidized region 30 (e.g., having carbonyl groups, aldehyde groups, carboxylic acid groups and/or alcohol groups), a -carbonized. region 32 (e.g., having increased sp2'bonding, particularly aromatic carbon-carbon bonds and/or sp3 diamond-like carbon-carbon bonds), and a crosMinked region :44. In particular embodiments, the crosalinked region 34 is a region of increased polymer crosslinking that is bonded directly to th.e unmodified base polymer system and to the carbonized region 32. The carbonized region 32 is a band that typically includes- a high-level of sp -hybridized carbon atoms, e.g., greater than .25 percent sp3, greater than 40 percent., or CVOI1 greater than 50 percent sp3-hyridized carbon atoms, such as exists in ao diamond-like carbon (DI,C). The oxidized region 30 that is txynded to the carbonized
7 layer 32 and exposed to atmosphere includes an enhanced oxygen content relative to the base polymer system. The hard, scratch resistant nature of the carbonized region reduces pinhole formation, which can occur, e.g., during crimping of stents.
For example, a dust particle disposed between the stent and an outer balloon surface can be compressed into the balloon during the crimping, penetrating the balloon and forming a pinhole. The graduated multi-region structure of the modified region enhances adhesion of the modified layer to the unmodified base polymer, reducing the likelihood of delamination. In addition, the graduated nature of the structure and low thickness of the modified region relative to the overall wall thickness enables the balloon to substantially maintain mechanical properties of the unmodified balloon.
The presence of various regions, e.g., carbonized regions, oxidized regions, and cross linked regions, can be detected using, e.g., infrared, Raman and UV-vis spectroscopy.
For example, Raman spectroscopy measurements are sensitive to changes in translational symmetry and are often useful in the study of disorder and crystallite formation in carbon films. In Raman studies, graphite can exhibit a characteristic peak at 1580 cm -I (labeled 'G' for graphite). Disordered graphite has a second peak at 1350 cm-' (labeled 'D' for disorder), which has been reported to be associated with the degree of sp3 bonding present in the material. The appearance of the D-peak in disordered graphite can indicate the presence in structure of six-fold rings and clusters, thus indicating the presence of sp3 bonding in the material. XPS is another technique that has been used to distinguish the diamond phase from the graphite and amorphous carbon components. By deconvoluting the spectra, inferences can be made as to the type of bonding present within the material. This approach has been applied to determine the sp3/sp2 ratios in DLC material (see, e.g., Rao, Surface &
Coatings Technology 197, 154-160, 2005.
The balloon can be modified using plasma immersion ion implantation ("P111"). Referring to FIGS. 3A and 3B, during P111, charged species in a plasma 40, such as a nitrogen plasma, are accelerated at high velocity towards balloons 15 that are in a nominal, unexpanded state, and which are positioned on a sample holder 41.
Acceleration of the charged species of the plasma towards the balloons is driven by an
For example, a dust particle disposed between the stent and an outer balloon surface can be compressed into the balloon during the crimping, penetrating the balloon and forming a pinhole. The graduated multi-region structure of the modified region enhances adhesion of the modified layer to the unmodified base polymer, reducing the likelihood of delamination. In addition, the graduated nature of the structure and low thickness of the modified region relative to the overall wall thickness enables the balloon to substantially maintain mechanical properties of the unmodified balloon.
The presence of various regions, e.g., carbonized regions, oxidized regions, and cross linked regions, can be detected using, e.g., infrared, Raman and UV-vis spectroscopy.
For example, Raman spectroscopy measurements are sensitive to changes in translational symmetry and are often useful in the study of disorder and crystallite formation in carbon films. In Raman studies, graphite can exhibit a characteristic peak at 1580 cm -I (labeled 'G' for graphite). Disordered graphite has a second peak at 1350 cm-' (labeled 'D' for disorder), which has been reported to be associated with the degree of sp3 bonding present in the material. The appearance of the D-peak in disordered graphite can indicate the presence in structure of six-fold rings and clusters, thus indicating the presence of sp3 bonding in the material. XPS is another technique that has been used to distinguish the diamond phase from the graphite and amorphous carbon components. By deconvoluting the spectra, inferences can be made as to the type of bonding present within the material. This approach has been applied to determine the sp3/sp2 ratios in DLC material (see, e.g., Rao, Surface &
Coatings Technology 197, 154-160, 2005.
The balloon can be modified using plasma immersion ion implantation ("P111"). Referring to FIGS. 3A and 3B, during P111, charged species in a plasma 40, such as a nitrogen plasma, are accelerated at high velocity towards balloons 15 that are in a nominal, unexpanded state, and which are positioned on a sample holder 41.
Acceleration of the charged species of the plasma towards the balloons is driven by an
8 electrical potential difference between the plasma and an electrode under the balloon.
Upon impact with a balloon, the charged species, due to their high velocity, penetrate a distance into the balloon and react with the material of the balloon, forming the regions discussed above. Generally, the penetration depth is controlled, at least in part, by the potential difference between the plasma and the electrode under the balloon. If desired, an additional electrode, e.g., in the form of a metal grid 43 positioned above the sample holder, can be utilized. Such a metal grid can be advantageous to prevent direct contact of the balloons with the rf-plasma between high-voltage pulses and can reduce charging effects of the balloon material.
Referring to FIG. 3C, an embodiment of a PIII processing system 80 includes a vacuum chamber 82 having a vacuum port 84 connected to a vacuum pump and a gas source 130 for delivering a gas, e.g., nitrogen, to chamber 82 to generate a plasma.
System 80 includes a series of dielectric windows 86, e.g., made of glass or quartz, sealed by o-rings 90 to maintain a vacuum in chamber 82, Removably attached in some of the windows 86 are RF plasma sources 92, each source having a helical antenna 96 located within a grounded shield 98, The windows without attached RF
plasma sources are usably, e.g. as viewing ports into chamber 82. Each antenna electrically communicates with an RF generator 100 through a network 102 and a coupling capacitor 104. Each antenna 96 also electrically communicates with a tuning capacitor 106. Each tuning capacitor 106 is controlled by a signal D, D', D"
from a controller 110. By adjusting each tuning capacitor 106, the output power from each RF antenna 96 can he adjusted to maintain homogeneity of the generated plasma.
The regions of the balloons directly exposed to ions from the plasma can he controlled by rotating the balloons about their axis. The balloons can be rotated continuously during treatment to enhance a homogenous modification of the entire balloon.
Alternatively, rotation can he intermittent, or selected regions can he masked to exclude treatment of those masked regions. Additional details of PIII is described hy Chu, U.S.
Patent No.
6,120,260; Brukner, Surface and Coatings Technology, 103-104, 227-230 (1998);
and Kutsenko, Acta Materialia 52, 4329-4335 (2004).
Upon impact with a balloon, the charged species, due to their high velocity, penetrate a distance into the balloon and react with the material of the balloon, forming the regions discussed above. Generally, the penetration depth is controlled, at least in part, by the potential difference between the plasma and the electrode under the balloon. If desired, an additional electrode, e.g., in the form of a metal grid 43 positioned above the sample holder, can be utilized. Such a metal grid can be advantageous to prevent direct contact of the balloons with the rf-plasma between high-voltage pulses and can reduce charging effects of the balloon material.
Referring to FIG. 3C, an embodiment of a PIII processing system 80 includes a vacuum chamber 82 having a vacuum port 84 connected to a vacuum pump and a gas source 130 for delivering a gas, e.g., nitrogen, to chamber 82 to generate a plasma.
System 80 includes a series of dielectric windows 86, e.g., made of glass or quartz, sealed by o-rings 90 to maintain a vacuum in chamber 82, Removably attached in some of the windows 86 are RF plasma sources 92, each source having a helical antenna 96 located within a grounded shield 98, The windows without attached RF
plasma sources are usably, e.g. as viewing ports into chamber 82. Each antenna electrically communicates with an RF generator 100 through a network 102 and a coupling capacitor 104. Each antenna 96 also electrically communicates with a tuning capacitor 106. Each tuning capacitor 106 is controlled by a signal D, D', D"
from a controller 110. By adjusting each tuning capacitor 106, the output power from each RF antenna 96 can he adjusted to maintain homogeneity of the generated plasma.
The regions of the balloons directly exposed to ions from the plasma can he controlled by rotating the balloons about their axis. The balloons can be rotated continuously during treatment to enhance a homogenous modification of the entire balloon.
Alternatively, rotation can he intermittent, or selected regions can he masked to exclude treatment of those masked regions. Additional details of PIII is described hy Chu, U.S.
Patent No.
6,120,260; Brukner, Surface and Coatings Technology, 103-104, 227-230 (1998);
and Kutsenko, Acta Materialia 52, 4329-4335 (2004).
9 .:Palloon modification is eontrolle.d to prodncea desired type of inedificafion:at a selected depth, The nature .and depthof the ModifiCation iSalso controlled :to adjust the :overall meehanical properties of theballoon, laparticular embodiments,:
the modification iscontrolled SO that the mechanical properties, .suelt as.
tenSileStrengtk elopg4tori.and modulus of elaSticity of the base polymer system are .not substantially thanged by tbe.preseTipe :Of the.rnodifieati on I.n enthodimems, the .tensile strength, elongation and -modulus. of elasticity o.f the: modified .pOlYiner ìs substantially the .Sartie las or greater than those respective values' ofthe uninodified polymer. In addition, :the mOdification is controlled ..so that 'balloon. pertbrmanee properties, ucb. as burst.
.Strength, withdrawal force, torque and securement,..are not sUbStatitially changed, or are imprOved by the:preset:lee:of themodifieati on:
Thetype. and depth Of modification is.. controlled: in the .P.M.proceSs .by selection of the type :of ioo,. the ion energy and ion dose, to embodiments, a three Sub-.
region modifieation as described .above is provided. In .other embodimentsõ.theremay be more, or less than threesubtregions.fonned=by .controlling the PHI process parameters, or by post processing to remove one ot.more /aye's by, ..e.g., solvent diSsolution,or inectunietillyrertiOving.layers by cutting, abrasion, or hot treating. lin.
p.artienlar, 4 higherion.energyand dose enhances the formation of carbonized regions, particularly:regions .),Vith DLE or graphític eontponents. Lo erthOdimehts, the ion.
energy is about 5 or greater, $14ehas 2.5. keV. or greater, e.g. about 3ØkeVot greater and abont..75'keV or less Tbeion..dosage in.einbodittienta.iS in the range of :about 1 x or greater, surh..as 1 X 10-1.6ionsicit2 or gjeater,:e.g,.abotit 5 X 1916 ionsicteor greater, and .about X 1019.ionsfcm2 or less. 'The. oxidized region can be characterized, .and the process .conditions .modified basedonlFTIR ATR
spectrOseopy results .on: carbonyl.gmup .and hydroXyl group absorptions. . s.o, the .crosslinked region eanbe. eharacterized using Frm t Rspectroscppy.; UV-vis spectroseopy and.
Raman. spectroscopy by .analyzing C=C group :absorptions, and the process eonditions.
modifml based :on the.restilts. ho. aditiok.the process .eorghtiOs can he :modified based .on Int analysis of the gel fracfion .of thecrosslitiked region. The gel fraction of a:sample can be tieternfirtedby extraction of the .=sample in a boiling scilVent..SUCh as o-xylene. for 24 'hours tising,.
a..Soxliet extractor. . After 24 hours,: the :solvent: is removed from the extracted .material, and then the sample is further dried in a vacuum oven at 50 C ntiI a constant weight is achieved. 'liege! fraction is the difference.
between the initial weight of the sample and the dry weight of the sample that was extracted, divided by the total initial weight of the sample, In embodiments, the thickness Tm Of the modified region 28 is less than about 1500 .am, e.g., less than about 1000 tun, less than about 750 nm, less than about 500 nm, lt,..ss than about 250 nm, less than about 150 run, less than -about 100 rim or less than about 50 TIM. In embodiments, the oxidized region 30 can have a thickness T1 of less than about 5 inn, e.g., less than about 2 tim or less than about 1 ran.
In etribodiments, the carbonized region 32 can have a thickness T2 of less than about 500 rim, e.g., less than about 350 am, less than about 250 nin, less than about 150 run or less than about 100 mm, and can occur at a depth -from outer surface-22 of less than 10 nm, e.g., less than 5 mn or less than 1 nm. in embodiments, the crosslinked region 34 has a thickness T3 of less than about 1500 rim, e.g., less than about 1000 nm, or less th.an about 500 nm, and can occur at a depth from outer surface 22 of iess than about 500 nm, e.g., less than about 350 TIM, 1CSS than about 250 nm or less than about 100 11111.
In embodiments, burst strength, withdrawal force, torqueand socutement of the modified balloons are within about 35% oriess, e.g. + 15%, e.g. 5% or 20 of those values for the unmodified balloon. In particular embodiments, withdrawal force and securement are increased by about 15% or more, e.g. about 25% or more by modification of the balloon wall. To minimize the influence of the modified region on overall mechanical properties of the balloon., the depth of the modification can be selected so that the mechanical properties of the modified region do not substantially 25 affect the overall mechanical propertiesof the balloon. In embodiments,.
the thickness Tm of the modified region is about 1% or less, e.g. about. 0.5% or less or about 0.05%
or more, of the thickness TB of the unmodified base polymer system. In embodiments, the balloon CLIT1 be modified to vary the mechanical properties of the polymer or the balloon performance. For example, a balloon stiffness can be 30 enhanced by modifying the balloon to include, arelativelythick cathinized or crosslinked layer. in embodiments, the thickness Tm of the modified layer can be 11.
4b01.4:251,.4.t)r Marc, .p.g.
to.90c.'/.0 of the overall thickness T f thetatimodifti base.' polymer system In ettibodiments, the wall has: art overall. thickness o.f less tlian abOut (LOOS:inch, e.l.tõ less than: about 0.0025 inch, less than .abont.0,Q02 inch, les.s than aboutØ001 ineh (telesstban about .ØQ905 inch.
.11). ,P411,iattar 41n L'AltdiblentS the..hallooti is sh?..ed for use inthe vascular system, such as die cormary..arteriesfor'atigioplasty and/Or Stem delivery. The balloonhas.:a burst strength ofIthotit.5bar...or more,. e.g.,.abotit 15:bar or mare.
Thi!'.1base .po trier system is, e.g., &polymer;a polyitner blends cr layer'strueture.ofpolymer that providm desirable properties te.. the balloon, particular -embodiments, the base pi ye includes:a low .distendinility, high burst :strength polymer. .Polytners ineludebiagially oriented .polymers,. thernitiplastic elaStomers, engineering. thermoplastic elastomers, polyethylene's, PolYethYletietereplithalate(PKr..), polybutylmcs, polyainides.(e.g.
nylon 66), polyetherblock :amides .(e.g.,.:PEBAX"), polyprop:vlette(PY),polYstyrene (PS)., polyvinyl ChlOrides. (PVC), poi ytettatioortthytetie. (eTFE.),.
polyinethyltnelhaciylate.(PMMA), polyimide,.polyearbonate (PC),..polyisoptene lubber (PD., nitrile..rubbarsõ silitoteruhhers,:..'ethyleno-propyle.ne client rubbers (UM), butyl.rubbeil4 (MI, thermoplastic polyurethanes (Pt.3..)..(e,g. those based. on a gy ether and an isocyanate,..such as PTiLLETHANte;), In particular embodiments, a poly(etlier-amide) blook...eopolymer .having :the general formula o.
.in Which :PA represents a polyamide segment, e.gnylon..1.2, and PE, represents a pOlyether segpient,.:e::g.,.:poiy(tetramethylene glyeol)isIitilized. Such polymers are .coranterciallyaVailable from AT)FINA under the traderiaine.PEBAX!.
:Kt.Jerring to FIGS. ..4A and 413, in a particular embodimwt,:the base polynter 25. :iyStelli is fOrrned by totigtrudingimultiplo polymer layers a hcsan.e r differpnt pob..mer, A balloon 61.irte1tides.afg.,all.f0 that has .a ti. rst polymei=
layer.63 and a second pol yrne.r layer 65 that are bonded 'at.: an irite.rface 67. Balloon .i61 can he.
modified using:P1i to provide :a .modified balloOn 71, hi the embo.ditnent..shown...in FIG. 43, the first layer 63 and interface 67 of balloon 61 is modified with PHI to produce modified layer 73 and modified interface 75 of balloon 71. In this particular embodiment, layer 65 is substantially unmodified. Modification of the first layer 63 of balloon 61 provides a hard, pinhole resistant layer, while modification across the interface enhances adhesion between the adjacent layers in balloon 71. In embodiments such as this, tie layers can be reduced or avoided, In particular embodiments, the balloon cars have three or more layers, e.g., five, seven or more layers, e.g., with ail or just some of the layers being modified. Balloons formed of coextruded polymer layers are described in Wang, U.S. Patent Nos. 5,366,442 and 5,195,969, Hamlin, U.S. Patent No. 5,270,086, and Chin, U.S. Patent No. 6,951 ,675.
The balloon can used, e.g., to deliver a stent. The stent can be a stent such as a biocredible stent that has been treated using PIII. Suitable stents are described in U.S.
Published Patent Application No. 2007/0191931, entitled "BIOERODIBLE
ENDOPROSTHESES AND METHODS OF MAKING THE SAME".
A balloon can also be modified to provide a desirable surface morphology.
Referring to FIG. 5 A, & balloon, surface 50 prior to modification is illustrated to include a relatively flat and featureless polymer profile (balloon is formed from PEBAX 7033). Referring to FIG. 5B, alter modification by PIII, the surface includes a plurality of fissures 52. The size and density of the fissures can affect surface roughness, which can enhance the friction between the stent and balloon, improving retention of the stent during delivery into the body. Referring to FIG. 5C, in some embodiments, the fracture density is such that non-fractured "islands" 53 of surface defined by fracture lines 52 are not more than about 20 pm2, e.g., not more than about
the modification iscontrolled SO that the mechanical properties, .suelt as.
tenSileStrengtk elopg4tori.and modulus of elaSticity of the base polymer system are .not substantially thanged by tbe.preseTipe :Of the.rnodifieati on I.n enthodimems, the .tensile strength, elongation and -modulus. of elasticity o.f the: modified .pOlYiner ìs substantially the .Sartie las or greater than those respective values' ofthe uninodified polymer. In addition, :the mOdification is controlled ..so that 'balloon. pertbrmanee properties, ucb. as burst.
.Strength, withdrawal force, torque and securement,..are not sUbStatitially changed, or are imprOved by the:preset:lee:of themodifieati on:
Thetype. and depth Of modification is.. controlled: in the .P.M.proceSs .by selection of the type :of ioo,. the ion energy and ion dose, to embodiments, a three Sub-.
region modifieation as described .above is provided. In .other embodimentsõ.theremay be more, or less than threesubtregions.fonned=by .controlling the PHI process parameters, or by post processing to remove one ot.more /aye's by, ..e.g., solvent diSsolution,or inectunietillyrertiOving.layers by cutting, abrasion, or hot treating. lin.
p.artienlar, 4 higherion.energyand dose enhances the formation of carbonized regions, particularly:regions .),Vith DLE or graphític eontponents. Lo erthOdimehts, the ion.
energy is about 5 or greater, $14ehas 2.5. keV. or greater, e.g. about 3ØkeVot greater and abont..75'keV or less Tbeion..dosage in.einbodittienta.iS in the range of :about 1 x or greater, surh..as 1 X 10-1.6ionsicit2 or gjeater,:e.g,.abotit 5 X 1916 ionsicteor greater, and .about X 1019.ionsfcm2 or less. 'The. oxidized region can be characterized, .and the process .conditions .modified basedonlFTIR ATR
spectrOseopy results .on: carbonyl.gmup .and hydroXyl group absorptions. . s.o, the .crosslinked region eanbe. eharacterized using Frm t Rspectroscppy.; UV-vis spectroseopy and.
Raman. spectroscopy by .analyzing C=C group :absorptions, and the process eonditions.
modifml based :on the.restilts. ho. aditiok.the process .eorghtiOs can he :modified based .on Int analysis of the gel fracfion .of thecrosslitiked region. The gel fraction of a:sample can be tieternfirtedby extraction of the .=sample in a boiling scilVent..SUCh as o-xylene. for 24 'hours tising,.
a..Soxliet extractor. . After 24 hours,: the :solvent: is removed from the extracted .material, and then the sample is further dried in a vacuum oven at 50 C ntiI a constant weight is achieved. 'liege! fraction is the difference.
between the initial weight of the sample and the dry weight of the sample that was extracted, divided by the total initial weight of the sample, In embodiments, the thickness Tm Of the modified region 28 is less than about 1500 .am, e.g., less than about 1000 tun, less than about 750 nm, less than about 500 nm, lt,..ss than about 250 nm, less than about 150 run, less than -about 100 rim or less than about 50 TIM. In embodiments, the oxidized region 30 can have a thickness T1 of less than about 5 inn, e.g., less than about 2 tim or less than about 1 ran.
In etribodiments, the carbonized region 32 can have a thickness T2 of less than about 500 rim, e.g., less than about 350 am, less than about 250 nin, less than about 150 run or less than about 100 mm, and can occur at a depth -from outer surface-22 of less than 10 nm, e.g., less than 5 mn or less than 1 nm. in embodiments, the crosslinked region 34 has a thickness T3 of less than about 1500 rim, e.g., less than about 1000 nm, or less th.an about 500 nm, and can occur at a depth from outer surface 22 of iess than about 500 nm, e.g., less than about 350 TIM, 1CSS than about 250 nm or less than about 100 11111.
In embodiments, burst strength, withdrawal force, torqueand socutement of the modified balloons are within about 35% oriess, e.g. + 15%, e.g. 5% or 20 of those values for the unmodified balloon. In particular embodiments, withdrawal force and securement are increased by about 15% or more, e.g. about 25% or more by modification of the balloon wall. To minimize the influence of the modified region on overall mechanical properties of the balloon., the depth of the modification can be selected so that the mechanical properties of the modified region do not substantially 25 affect the overall mechanical propertiesof the balloon. In embodiments,.
the thickness Tm of the modified region is about 1% or less, e.g. about. 0.5% or less or about 0.05%
or more, of the thickness TB of the unmodified base polymer system. In embodiments, the balloon CLIT1 be modified to vary the mechanical properties of the polymer or the balloon performance. For example, a balloon stiffness can be 30 enhanced by modifying the balloon to include, arelativelythick cathinized or crosslinked layer. in embodiments, the thickness Tm of the modified layer can be 11.
4b01.4:251,.4.t)r Marc, .p.g.
to.90c.'/.0 of the overall thickness T f thetatimodifti base.' polymer system In ettibodiments, the wall has: art overall. thickness o.f less tlian abOut (LOOS:inch, e.l.tõ less than: about 0.0025 inch, less than .abont.0,Q02 inch, les.s than aboutØ001 ineh (telesstban about .ØQ905 inch.
.11). ,P411,iattar 41n L'AltdiblentS the..hallooti is sh?..ed for use inthe vascular system, such as die cormary..arteriesfor'atigioplasty and/Or Stem delivery. The balloonhas.:a burst strength ofIthotit.5bar...or more,. e.g.,.abotit 15:bar or mare.
Thi!'.1base .po trier system is, e.g., &polymer;a polyitner blends cr layer'strueture.ofpolymer that providm desirable properties te.. the balloon, particular -embodiments, the base pi ye includes:a low .distendinility, high burst :strength polymer. .Polytners ineludebiagially oriented .polymers,. thernitiplastic elaStomers, engineering. thermoplastic elastomers, polyethylene's, PolYethYletietereplithalate(PKr..), polybutylmcs, polyainides.(e.g.
nylon 66), polyetherblock :amides .(e.g.,.:PEBAX"), polyprop:vlette(PY),polYstyrene (PS)., polyvinyl ChlOrides. (PVC), poi ytettatioortthytetie. (eTFE.),.
polyinethyltnelhaciylate.(PMMA), polyimide,.polyearbonate (PC),..polyisoptene lubber (PD., nitrile..rubbarsõ silitoteruhhers,:..'ethyleno-propyle.ne client rubbers (UM), butyl.rubbeil4 (MI, thermoplastic polyurethanes (Pt.3..)..(e,g. those based. on a gy ether and an isocyanate,..such as PTiLLETHANte;), In particular embodiments, a poly(etlier-amide) blook...eopolymer .having :the general formula o.
.in Which :PA represents a polyamide segment, e.gnylon..1.2, and PE, represents a pOlyether segpient,.:e::g.,.:poiy(tetramethylene glyeol)isIitilized. Such polymers are .coranterciallyaVailable from AT)FINA under the traderiaine.PEBAX!.
:Kt.Jerring to FIGS. ..4A and 413, in a particular embodimwt,:the base polynter 25. :iyStelli is fOrrned by totigtrudingimultiplo polymer layers a hcsan.e r differpnt pob..mer, A balloon 61.irte1tides.afg.,all.f0 that has .a ti. rst polymei=
layer.63 and a second pol yrne.r layer 65 that are bonded 'at.: an irite.rface 67. Balloon .i61 can he.
modified using:P1i to provide :a .modified balloOn 71, hi the embo.ditnent..shown...in FIG. 43, the first layer 63 and interface 67 of balloon 61 is modified with PHI to produce modified layer 73 and modified interface 75 of balloon 71. In this particular embodiment, layer 65 is substantially unmodified. Modification of the first layer 63 of balloon 61 provides a hard, pinhole resistant layer, while modification across the interface enhances adhesion between the adjacent layers in balloon 71. In embodiments such as this, tie layers can be reduced or avoided, In particular embodiments, the balloon cars have three or more layers, e.g., five, seven or more layers, e.g., with ail or just some of the layers being modified. Balloons formed of coextruded polymer layers are described in Wang, U.S. Patent Nos. 5,366,442 and 5,195,969, Hamlin, U.S. Patent No. 5,270,086, and Chin, U.S. Patent No. 6,951 ,675.
The balloon can used, e.g., to deliver a stent. The stent can be a stent such as a biocredible stent that has been treated using PIII. Suitable stents are described in U.S.
Published Patent Application No. 2007/0191931, entitled "BIOERODIBLE
ENDOPROSTHESES AND METHODS OF MAKING THE SAME".
A balloon can also be modified to provide a desirable surface morphology.
Referring to FIG. 5 A, & balloon, surface 50 prior to modification is illustrated to include a relatively flat and featureless polymer profile (balloon is formed from PEBAX 7033). Referring to FIG. 5B, alter modification by PIII, the surface includes a plurality of fissures 52. The size and density of the fissures can affect surface roughness, which can enhance the friction between the stent and balloon, improving retention of the stent during delivery into the body. Referring to FIG. 5C, in some embodiments, the fracture density is such that non-fractured "islands" 53 of surface defined by fracture lines 52 are not more than about 20 pm2, e.g., not more than about
10 lam2, or not more than about 5 lam2. In embodiments, the fracture lines are, e.g., less 10 pm wide, e.g., less than 5 p,m, less than 2.5 pm, less than 1 jam, less than 0.5 [tm, or even less than 0.1 lam wide. The fissures or fracture lines cars also be utilized as a reservoir for a therapeutic agent, such as an anti-thrombogeme agent, an anesthetic agent or an anti-inflammatory agent. A suitable agent is paclitaxel. The agent can be applied to the balloon surface by soaking or dipping. Other agents are described in U.S. Published Patent Application No. 2005/0215074. The balloon can be coated with a protective or release layer such as a salt, sugar or sugar derivative.
Suitable layers are described in U.S. Patent No. 6,939,320.
Further embodiments are in the following examples.
EXAMPLES
Materials Tests are conducted on 2 and 4 mm diameter balloons of PEBA X 7033, having a Shore D hardness of 69, are manufactured by Boston Scientific, Natick, MA, Before PIII treatment, the balloons are cleaned with alcohol. Tests are also conducted on 20 x 20 x 1 mm PEBAX 7033 plates which are made by pressing PEBAX 7033 pellets between polished PTFE plates at 250-300 C for several minutes. Low-density polyethylene (LDPH) films having a thickness of 50 mkm are used as purchased, as are silicon plates having a thickness of 1 mm, Methods and Equipment The large chamber of Rossendorf Research Center is used for PHI (see, e.g., Guenzel, Surface & Coatings Technology, 136, 47-50, 2001, or Guenzel, i Vacuum Science & Tech. B, 17(2), 895-899, 1999). The pressure of residual air is 10 Pa and the working pressure of nitrogen during PIII was 10' Pa. Plasma is generated by a radio frequency generator operating at 13.56 MHz. High voltage pulses of 5 ps duration and 30, 20, 10 and 5 kV peak voltages is used. Pulse repetition frequency from 0.2 Hz to 200 Hz is used to prevent overheating. The PIII treatment of the samples are carried out with doses ranging from 5-10'4 to 10'7 ions/cm'. The position of the balloons are fixed using a sample holder. Balloons are turned three times (120 degrees each time) during treatment so as to homogeneously treat the outer surface of the balloons. An additional electrode in the form of a metal grid is mounted on the top of the sample holder to prevent direct contact of the samples with rf-plasma between high voltage pulses .and to prevent chargiaag of the polymeric material. FTIR
Ant spectra can be recorded on either a Nicolet 230 with a diamond ATR crystal or on a Nicolet Magna 750 with a Ge AIR crystal. The number of scans is 100 and resolution is 2 cm-'. The spectra are analyzed with Nieolet OMN1C software. mi transmission spectra can be recorded with a 10 inn step in 200-700 nm.
wavelength s.3.-sectral region. The optical density scale is used fir quantitative analysis to determine the homogeneity of the dose distribution along the polymer surface.
The regime of spectral mapping on xy-coordinates is used for analysis of dose distribution to homogeneity on a polymer surface. The space resolution at the mapping is approximately 4 x 4 min. Micro-Raman spectra are recorded in hackseattering mode, excited by Nd:YAO laser irradiation (.2e), A=532.14 run), on a jobin Yvon HR800 with 1..abRam analysis software. An optical microscope is used for focusing of the laser beam. and for collection of the Raman scattered light. The. intensity alma bean) is controlled to prevent overheating of the samples. Spectral resolution is 4 cm-1. The number of scans acquired is between 100 and 4000, the actual number depending upon the signal-to-noise for the sample.
Tensile tests are perthmed on a2.wick tensile machine; PEBAX*7033 strips of 30 x 2 x 0.03 mm are used. For strips, the balloons are cut using multi-blade knife including six blades joined together through 2 mm plates. The ends Utile strips are bonded to aluminum foil lasing epoxy glue for strong mechanical fixing to the clamps.
Five strips are used for one sample analysis. Load direction of the test corresponds to the longitudinal aXiS of the balloon. A crosshead speed of 5 mmimin is applied.. The analysis of the results is done by strain-stress diagram. 1N/10dt:his, elongation and 2s stress at breaking are analyzed. Modulus is determined by the beginning of the linear Ind of strain-stress curve.
S.cratch tests are performed with a tester that includes a table having a fixed sample and a balance with a diamond indenter having a tip that is 1 micron.
The table moves with .a speed of 0.15 mintsec. The diamond indenter can. be loaded with 1, 2, ao 5, 10,20 and 50 grams :of weight. Plates of PEBAX* .7033 are used tbr the scrateh test. The depth and width of the scratch is determined by optical profilometry. The scratch tester is calibrated on polyethylene, polyamide and polytetrafluorethylene plates. Hardness is determined by the AIN: method in contact mode using a silicon tip having a 20 an diameter and a cantilever with a constant of 80 nrslinni (see, e.g., Prikryl, Surface di Coatings 'technology, 200, 4(8-471, 2005, the entire disclosure of which is hereby incorporated by reference herein).
.fitrnetural changes in 1EBAX4' 7033 Samples .After Treatment with.PIII
FIG 6 is a series of FTIR. ATR spectra of PEBAXs 7033 films taken from 1850 em.1 to 900 tat'l after PHI treatinent at 30 keV. The bottom spectrum is the lo untreated film, and the other spectra are films treated respectively with 5 X 1014,1015, 5 X 1015, 1016, 5 X 1016 and 1017 ionsiem2. A broadening of 1633 cm-1 peak and the appearance -(yl. a doublet at 1720/1737 011'1 with PEI dose is believed caused by new, overlapping lines in the regions of 1650-1750 errfl. These new lines are vibrations of carbon-carbon double limds and carbon-oxygen double- bonds. The appearance of such lines is connected with the carbonization and oxidation the PEBAXs polymer under the ion source.
FIG 7 is a series of FTIR ATR spectra of PEB.AX4 7033 films taken from 3700 ern"1 to 2550 enfl -after P111 treatment at 30 keV. The bottom spectrum is the untreated film, and the other spectra are films treated respectively with. 5 X
1014, 1015, 2D 5 X 10150016., 5 X 1016 and. 1017 ionsicm2. A new line at 3600-320.0 em-1 region is observed in spectre-1. This broad peak corresponds to 0-H vibrations of hydroxyl groups. While 0-1-1 groups exist in the untreated macrornolecules of PEBAXs (at chain endS), their concentration is much lower than after PHI treatment. The appeanmce of intensive 0-11 lines in the spectra of the treated samples results from depolymerization processes in -which broken. polymer thain ends react with oxygen, effectively increasing the 041 concentration in the sample.
MG, 8 is a series of Raman spectra of PEBAXs 7033 films taken from 1900 ernT1 to 775 cm-1 after P111 treatment at 20 keV, The bottom Spectrum is the untreaaxl film, and the other spectra are films treated respectively with 5. X 1.014, 1015, 5 X 1015, iOu':and 5 X. 1016 ionsicin2. ln the spectrum of the -untreattx1PEBAe, a lines at 1645, 1446, 1381, 1305, 1121 , 1074 cm-1 corresponded to the vibrations of polyamide-polyether macromolecule (PEBAX'). In spectra of treated samples, the intensity of such lines decreases with increasing PIII dose, and a new wide peak centered at 1510 cm-1 appears. This peak corresponds to vibrations of amorphous carbon. At high doses, the vibrations associated with the PEBAX essentially disappear and are replaced by the broad peak, associated with amorphous diamond.
These strong changes in the Raman spectra is observed only in outer portions of the film, indicating that only outer portions of the film are carbonized.
Defocusing, or shifting laser focus to deeper portions of the film gives the spectrum of untreated PEBAX .
FIG. 9 is a series of Raman spectra of PEBAX''' 7033 films taken from 1900 cm-' to 775 cm-' after PIII treatment at 30 keV. The bottom spectrum is the untreated film, and the other spectra are films treated respectively with 5 X 10'4, 10'5, 5 X le, 106, 5 X 1016 and 10'7 ions/cm". After PIII treatment with 30 keV energy, the Raman spectra of the samples treated at relatively low doses (5 X 10'4¨ 1 X 10'5 ions/cm') appear to be very similar to those shown in FIG. 8. However, at relatively high doses (5 X 101' and above), the Raman spectra contain two relatively sharp peaks at and 1350 cm'. These lines correspond to carbon in the form of graphitie structures and DLC structures. The peak at 1580 cm-' is called the G-peak and the peak at cm-' is called the D-peak. These lines are observed only in samples treated by ions with energy of 30 keV and at higher doses Raman spectra of diamond-like carbon materials are described by Shiao, Thin Solid Films, v. 283, 145-150 (1996).
Referring to FIGS. 10A and 10B, the structural transformations in PEBAX
under PIII can also be observed by transmission spectra in the ultraviolet and visual region. FIG. 10A is a series of UV-Vis transmission specira of PEBAX' films taken from 500 nm to 240 nm after PIII treatment at 20 keV, while FIG. 10B is a series after treatment at 30 keV. In both figures, the bottom spectrum is the untreated film, and the other spectra are turns treated respectively with 5 X 10'4, 1015, 5 X
10'5, 1016, 5 X
1016 and 10'7 ions/cm". P111 modification leads to a formation of additional overlapping lines in the spectra. From the spectra, it is apparent that the short wavelength lines have a stronger intensity than long wavelength lines and that the intensity of absorption increases with increasing dose. These additional lines are attributed to absorption of light by rt-eleetrons in unsaturated carbon-carbon structures, including condensed aromatic and polyene structures. An inerease in the .number of condensed structures shifts the position of the absorbing lines to red side of the spectrum, indicating the formation of long conjugated unsaturated carbon-carbon groups.
RefetTing to FIGS. II A and 11B, quantitative analysis of the unsaturated carbon-carbon structures in PEBAX 7033 fihns is done by optical density .at two separate s,vavelengths. Iri suet' an analysis, 250 nm corresponds to n 1 and 550 nm corresponds to n 4, where n is nuntber of conjugated aromatic structures. At low dose, the rate of unsaturated carhon-carbon structures collection is low.
However, a strong increase in absorption starts from a dose of about 1015 ions/cm:1. The formation Of T1 "z I structures starts at lower dose, and the highly conjugated carbon-carbon structures with 11 zzz 4 appears at higher dose.
Referring now to FIG 12, when comparing the UV spectra of PEBAX 7033 films and those of I.DPE, the FEBA.X* films have a lesser level of unsaturated carbon-carbon structures. Because transmission spectra do not contain absorption lines for initial films of PEBA)e films and LDM the optical density at 250 .nin can he interpreted as absorption only from the modified polymu region. Therefore, the value of the optical density at thesame dose of Pill can be used for quantitative comparison. The estimation of unsaturated carbon-carbon Structures itt PEBAX
films gives 68 +8% in. comparison with I.:DPE for all doses of PIII. This number means that approximately two-thirds of the PF.BAX takespart in formation of carbonized layer.
Referring to FIG: 13, the surface morphology-of the PEBAJe 7033 films change strongly at high dose of P111 treatment which is observable in photornicTographs. At low doseS :of treatment, the surface morphology does not significantly change. At dose of 1015 ionslan2, the surface co.ntains some cracks and fissures. However, at higher doses, an extensive network of cracks and fissures is observed. :Despite the crack and fissure network, peeling of the carbonized region from the bulk polymer is not observed.
Mechanical Properties of PEBA,le Films A.fter Treatment with Ulf Refening to FIG 14, stress-strain curves of Pill treated PEBA:e 7033 films are nearly identical to the corresponding stress-strain curves a untreated films. The curves of all PESAXs films tested are similar for all dose and energies:
Referring to FIG 15, strength at breaking also does not appear to change after P111 treatment. In addition, referring to FIGS. 16 and 17, .percent elongation at break and -modulus of elasticity are statistically unaffected by P111 treatment.
The thickness of the modified region (for these samples. estimated at. less Inn) relative to the thickness of the unmodified region for these samples estimated at around 30,000-nm) can be used to explain why Plif modification of PELiAX films -does not lead to significant changes in the mechanical properties tested of those films.
Surface Hardness of PEBAXP Films After PIII Treatment and Scratch Testing 16 Referring to FIG 21, a load curve for a silicon .plate is used as reference, and shows -typical deformation behavior of a cantilever on hard surface..
Note.that the slope of the curve is relatively steep (indicating a high modulus of elasticity) and little or no hysteresis occurs. In contrast, the load curve for untreated PEI3AX 7033 -film is not as steep (indicating a low modulus-of elasticity) and shows sigcant hysteresis. Initially, the PEBAX1 load curve goes lower, corresponding to deformation of the polymeric material under tip load, The unload curve corresponds to retrace movement of the tip, and sincethe load and unload curve are not identical, hysteresis is observed. likysteresis is caused by mech.anical energy loss due to tnovement and conformational transitions of polymer macrom.olecules under the load.
26 Such behavior is typical of relatively soft materials.
Refetring now to FIG 22, which is a load curve fbr a PEBAX* 7033 plate treated with Pill at a dose of 1.016 ionstem2 and 30 keV Note that the curve is generally steeper than the untreated plate curve shown in FIG 21, and the hysteresis has nearly disappeared. Such is curve is similar to the silicon reference curve, and is indicative that the PEBA.X4 plate has a hard surthee.
Referring to FIGS, 23 and 24, at relatively low doses, the load curve for "
treated PAX''= plates are more comOcx. Generally, there are two part i4 to these load, chives: The first part has steep curve, corresponding to a high MOdtall$, while the second part of the, atityp is pot ::as Am., corresponding to a lower moduli:1s. The' Observed comPlex character of the: load clime is believed to be caused by penetTation of the ADA tip through carbdnized region. At relatively low doses, this layer is not hard and thick enough to stop penetration by the tip.
FIG 25 Shows the dependence of the knodtilus of elaSticity Of the two parts of the load Curves tieseribedlibove. As can be s..v.p in FIG:25, the moddlos of elasticity io of the first part initially grows, µvhile the modulus:of elasticity of tk Second part Of the load turVe rettaing relatively cost. HoweVer: at a doSe of 110th ions/ere, the curve becomes linear and:the modulus of elasticity of each part becomes equal.
It :is believed that at this dose, the carbonized layer becomes hard enough to hold the tip load.
Referring to :FIGS. IS and I the results of scratch tests are shown. Different loads are apphed to Plif3AX1' 7033 plates treated at a variety of doses at 20 keV and 30 keV (dose in box is expivsSed trnuiltiples Of 10" ion$1eni2).
No:significant :differences are found between the modified and 3,mmodifi,ed PhiõBAX4 plates, ReferringflOW to FIG 20, also no Significant differences arer found ih the 2o hardness coefficient Of untreated PERAXt. plates when: compared to treated PliI3AX*
plates at a varictyof doses at 20 keY and 30 ke'V Since the thiekness of the:modified region is very small, the scratch tester is not sensitive enotigh to measure the Changes in the modified region. It is believed that the:diamond :indenter of thescratch tester penetrates through the thin modified region.
Referring to FIG 26, the modulus of elaStieity of the msboniod rcgion :dependS on the energy of penetrating ions, with higher energies :giving a higher moduhis. An especially high :modulus WaS Obsetved for an energy of 30 keV:
Sharp increase Of the modulus after 30 keV can be cOnfteeted With -forination ofgriphitie andiOLC structures.
liomogeneitv of Surface Hardness of PEBAX1' Films After Plii Treatment As discussed above, the hardness of the modified region is a function of dose and ion -energy. For homogeneity of surface hardness, the dose should be distributed equally over an entire surface. Because-the balloons are cylinder in fc.nin, the dose distribution has angular dependence, as shown in FIG. 27. Continuous rotation of the balloons during Pill treatment would provide the most homogenous surface hardness.
ffowever, if this is not possible, turning the balloons three times. 020 degrees each time) provides a reasonable homogeneity, with only a 10 percent deviation in the surflice hardness. To prepare the balloon samples desctibed above, the. three turns method was employed.
.Another reason for surface hardness inhomogeneity is plasma variation and corresponding variations of the ion &anent near the treated surface. This effect is caused by plasma density variations in volume and the charging &ex.:A of the polymer surface during high voltage pulse. This effect can be greatly reduced by positioning an additional electrode over balloon samples. For this purpose, a metal grid was utilized that was in electrical communication with the sample holden This arrangement allows ions to pass through the grid on their way to the balloon surlitee.
Dose distribution can be mapped using UV-vis spectra from 1.11E film. Such a mapping is shown in FIG 28.
As shown in FIGS. 28 and 29, the central part of the sample holder provides a dose that does not vary by more than 10%. The size of comtral part depends on size of additional electrodes. In the case of absence of die additional electrode, the dose distribution is uncontrolled. In the saniples discussed above, the area of homogenous.
dose has a diameter of approximately 50 mm. The balloons discussed above are all -treated in the central portion of the sample holder.
Withdrawal, Burst. Torque and Securement for Unmodified and Modified Balloons 'fbe table below provides data for balloon withdrawal, burst, torque and securement for unmodified and modified balloons. 'Me modified balloons are treated with Mlles described above using a dose of I0 ions/en-112 at 30 keV.
BALLOON PROPERTY UNMODIFIED MODIFIED BALLOON
Balloon Withdrawal Force 115 grams 81 grams Average Burst Pressure 293 PSI 294 PSI
Torque 1.07 N(mm) 1.26 N(mm) Securement 0.50 LB 0.96 LB
Balloon, withdrawal force Is measured using the method outlined by Devens, published U.S. Patent Application Publication No. 2004/0210211. Briefly, balloon withdrawal force is measured by determining the force required to remove a balloon from a torturous path defined by a polymer tube. Forces on the catheter and the tube can be measured by a series of transducers, as described by Devens. Torque is measured by turning the balloon in the same torturous path as used tor the balloon withdrawal force test, and determining the resistance to rotation. Average burst strength is measured by determining an inflation pressure at which the balloon bursts at 20 C, US described in Wang, U.S. Patent No. 6,171,278, and Levy, U.S.
Patent No. 4,490,421. Securement is measured using ASTM F2393-04.
In embodiments, the balloons can be used in various vascular or nonvascular applications. Exemplary applications include neuro, carotid, esophageal, or ureteral.
After treatment as described above, the balloon cars be further processed, e.g., to include a further coating, e.g., a hydro gel, or a polymer matrix coating including a drug. In embodiments, a balloon can be treated with a drug, or a polymer matrix that includes a drug, and subsequently treated by ions to modify the drug, the matrix and/or underlying balloon. Such a treatment can enhance or retard release of the drug from the balloon. In embodiments, other medical devices, e.g., coextruded medical devices, such as coextruded shafts, are treated by ions, as described above.
Still further embodiments arc in the following claims.
Suitable layers are described in U.S. Patent No. 6,939,320.
Further embodiments are in the following examples.
EXAMPLES
Materials Tests are conducted on 2 and 4 mm diameter balloons of PEBA X 7033, having a Shore D hardness of 69, are manufactured by Boston Scientific, Natick, MA, Before PIII treatment, the balloons are cleaned with alcohol. Tests are also conducted on 20 x 20 x 1 mm PEBAX 7033 plates which are made by pressing PEBAX 7033 pellets between polished PTFE plates at 250-300 C for several minutes. Low-density polyethylene (LDPH) films having a thickness of 50 mkm are used as purchased, as are silicon plates having a thickness of 1 mm, Methods and Equipment The large chamber of Rossendorf Research Center is used for PHI (see, e.g., Guenzel, Surface & Coatings Technology, 136, 47-50, 2001, or Guenzel, i Vacuum Science & Tech. B, 17(2), 895-899, 1999). The pressure of residual air is 10 Pa and the working pressure of nitrogen during PIII was 10' Pa. Plasma is generated by a radio frequency generator operating at 13.56 MHz. High voltage pulses of 5 ps duration and 30, 20, 10 and 5 kV peak voltages is used. Pulse repetition frequency from 0.2 Hz to 200 Hz is used to prevent overheating. The PIII treatment of the samples are carried out with doses ranging from 5-10'4 to 10'7 ions/cm'. The position of the balloons are fixed using a sample holder. Balloons are turned three times (120 degrees each time) during treatment so as to homogeneously treat the outer surface of the balloons. An additional electrode in the form of a metal grid is mounted on the top of the sample holder to prevent direct contact of the samples with rf-plasma between high voltage pulses .and to prevent chargiaag of the polymeric material. FTIR
Ant spectra can be recorded on either a Nicolet 230 with a diamond ATR crystal or on a Nicolet Magna 750 with a Ge AIR crystal. The number of scans is 100 and resolution is 2 cm-'. The spectra are analyzed with Nieolet OMN1C software. mi transmission spectra can be recorded with a 10 inn step in 200-700 nm.
wavelength s.3.-sectral region. The optical density scale is used fir quantitative analysis to determine the homogeneity of the dose distribution along the polymer surface.
The regime of spectral mapping on xy-coordinates is used for analysis of dose distribution to homogeneity on a polymer surface. The space resolution at the mapping is approximately 4 x 4 min. Micro-Raman spectra are recorded in hackseattering mode, excited by Nd:YAO laser irradiation (.2e), A=532.14 run), on a jobin Yvon HR800 with 1..abRam analysis software. An optical microscope is used for focusing of the laser beam. and for collection of the Raman scattered light. The. intensity alma bean) is controlled to prevent overheating of the samples. Spectral resolution is 4 cm-1. The number of scans acquired is between 100 and 4000, the actual number depending upon the signal-to-noise for the sample.
Tensile tests are perthmed on a2.wick tensile machine; PEBAX*7033 strips of 30 x 2 x 0.03 mm are used. For strips, the balloons are cut using multi-blade knife including six blades joined together through 2 mm plates. The ends Utile strips are bonded to aluminum foil lasing epoxy glue for strong mechanical fixing to the clamps.
Five strips are used for one sample analysis. Load direction of the test corresponds to the longitudinal aXiS of the balloon. A crosshead speed of 5 mmimin is applied.. The analysis of the results is done by strain-stress diagram. 1N/10dt:his, elongation and 2s stress at breaking are analyzed. Modulus is determined by the beginning of the linear Ind of strain-stress curve.
S.cratch tests are performed with a tester that includes a table having a fixed sample and a balance with a diamond indenter having a tip that is 1 micron.
The table moves with .a speed of 0.15 mintsec. The diamond indenter can. be loaded with 1, 2, ao 5, 10,20 and 50 grams :of weight. Plates of PEBAX* .7033 are used tbr the scrateh test. The depth and width of the scratch is determined by optical profilometry. The scratch tester is calibrated on polyethylene, polyamide and polytetrafluorethylene plates. Hardness is determined by the AIN: method in contact mode using a silicon tip having a 20 an diameter and a cantilever with a constant of 80 nrslinni (see, e.g., Prikryl, Surface di Coatings 'technology, 200, 4(8-471, 2005, the entire disclosure of which is hereby incorporated by reference herein).
.fitrnetural changes in 1EBAX4' 7033 Samples .After Treatment with.PIII
FIG 6 is a series of FTIR. ATR spectra of PEBAXs 7033 films taken from 1850 em.1 to 900 tat'l after PHI treatinent at 30 keV. The bottom spectrum is the lo untreated film, and the other spectra are films treated respectively with 5 X 1014,1015, 5 X 1015, 1016, 5 X 1016 and 1017 ionsiem2. A broadening of 1633 cm-1 peak and the appearance -(yl. a doublet at 1720/1737 011'1 with PEI dose is believed caused by new, overlapping lines in the regions of 1650-1750 errfl. These new lines are vibrations of carbon-carbon double limds and carbon-oxygen double- bonds. The appearance of such lines is connected with the carbonization and oxidation the PEBAXs polymer under the ion source.
FIG 7 is a series of FTIR ATR spectra of PEB.AX4 7033 films taken from 3700 ern"1 to 2550 enfl -after P111 treatment at 30 keV. The bottom spectrum is the untreated film, and the other spectra are films treated respectively with. 5 X
1014, 1015, 2D 5 X 10150016., 5 X 1016 and. 1017 ionsicm2. A new line at 3600-320.0 em-1 region is observed in spectre-1. This broad peak corresponds to 0-H vibrations of hydroxyl groups. While 0-1-1 groups exist in the untreated macrornolecules of PEBAXs (at chain endS), their concentration is much lower than after PHI treatment. The appeanmce of intensive 0-11 lines in the spectra of the treated samples results from depolymerization processes in -which broken. polymer thain ends react with oxygen, effectively increasing the 041 concentration in the sample.
MG, 8 is a series of Raman spectra of PEBAXs 7033 films taken from 1900 ernT1 to 775 cm-1 after P111 treatment at 20 keV, The bottom Spectrum is the untreaaxl film, and the other spectra are films treated respectively with 5. X 1.014, 1015, 5 X 1015, iOu':and 5 X. 1016 ionsicin2. ln the spectrum of the -untreattx1PEBAe, a lines at 1645, 1446, 1381, 1305, 1121 , 1074 cm-1 corresponded to the vibrations of polyamide-polyether macromolecule (PEBAX'). In spectra of treated samples, the intensity of such lines decreases with increasing PIII dose, and a new wide peak centered at 1510 cm-1 appears. This peak corresponds to vibrations of amorphous carbon. At high doses, the vibrations associated with the PEBAX essentially disappear and are replaced by the broad peak, associated with amorphous diamond.
These strong changes in the Raman spectra is observed only in outer portions of the film, indicating that only outer portions of the film are carbonized.
Defocusing, or shifting laser focus to deeper portions of the film gives the spectrum of untreated PEBAX .
FIG. 9 is a series of Raman spectra of PEBAX''' 7033 films taken from 1900 cm-' to 775 cm-' after PIII treatment at 30 keV. The bottom spectrum is the untreated film, and the other spectra are films treated respectively with 5 X 10'4, 10'5, 5 X le, 106, 5 X 1016 and 10'7 ions/cm". After PIII treatment with 30 keV energy, the Raman spectra of the samples treated at relatively low doses (5 X 10'4¨ 1 X 10'5 ions/cm') appear to be very similar to those shown in FIG. 8. However, at relatively high doses (5 X 101' and above), the Raman spectra contain two relatively sharp peaks at and 1350 cm'. These lines correspond to carbon in the form of graphitie structures and DLC structures. The peak at 1580 cm-' is called the G-peak and the peak at cm-' is called the D-peak. These lines are observed only in samples treated by ions with energy of 30 keV and at higher doses Raman spectra of diamond-like carbon materials are described by Shiao, Thin Solid Films, v. 283, 145-150 (1996).
Referring to FIGS. 10A and 10B, the structural transformations in PEBAX
under PIII can also be observed by transmission spectra in the ultraviolet and visual region. FIG. 10A is a series of UV-Vis transmission specira of PEBAX' films taken from 500 nm to 240 nm after PIII treatment at 20 keV, while FIG. 10B is a series after treatment at 30 keV. In both figures, the bottom spectrum is the untreated film, and the other spectra are turns treated respectively with 5 X 10'4, 1015, 5 X
10'5, 1016, 5 X
1016 and 10'7 ions/cm". P111 modification leads to a formation of additional overlapping lines in the spectra. From the spectra, it is apparent that the short wavelength lines have a stronger intensity than long wavelength lines and that the intensity of absorption increases with increasing dose. These additional lines are attributed to absorption of light by rt-eleetrons in unsaturated carbon-carbon structures, including condensed aromatic and polyene structures. An inerease in the .number of condensed structures shifts the position of the absorbing lines to red side of the spectrum, indicating the formation of long conjugated unsaturated carbon-carbon groups.
RefetTing to FIGS. II A and 11B, quantitative analysis of the unsaturated carbon-carbon structures in PEBAX 7033 fihns is done by optical density .at two separate s,vavelengths. Iri suet' an analysis, 250 nm corresponds to n 1 and 550 nm corresponds to n 4, where n is nuntber of conjugated aromatic structures. At low dose, the rate of unsaturated carhon-carbon structures collection is low.
However, a strong increase in absorption starts from a dose of about 1015 ions/cm:1. The formation Of T1 "z I structures starts at lower dose, and the highly conjugated carbon-carbon structures with 11 zzz 4 appears at higher dose.
Referring now to FIG 12, when comparing the UV spectra of PEBAX 7033 films and those of I.DPE, the FEBA.X* films have a lesser level of unsaturated carbon-carbon structures. Because transmission spectra do not contain absorption lines for initial films of PEBA)e films and LDM the optical density at 250 .nin can he interpreted as absorption only from the modified polymu region. Therefore, the value of the optical density at thesame dose of Pill can be used for quantitative comparison. The estimation of unsaturated carbon-carbon Structures itt PEBAX
films gives 68 +8% in. comparison with I.:DPE for all doses of PIII. This number means that approximately two-thirds of the PF.BAX takespart in formation of carbonized layer.
Referring to FIG: 13, the surface morphology-of the PEBAJe 7033 films change strongly at high dose of P111 treatment which is observable in photornicTographs. At low doseS :of treatment, the surface morphology does not significantly change. At dose of 1015 ionslan2, the surface co.ntains some cracks and fissures. However, at higher doses, an extensive network of cracks and fissures is observed. :Despite the crack and fissure network, peeling of the carbonized region from the bulk polymer is not observed.
Mechanical Properties of PEBA,le Films A.fter Treatment with Ulf Refening to FIG 14, stress-strain curves of Pill treated PEBA:e 7033 films are nearly identical to the corresponding stress-strain curves a untreated films. The curves of all PESAXs films tested are similar for all dose and energies:
Referring to FIG 15, strength at breaking also does not appear to change after P111 treatment. In addition, referring to FIGS. 16 and 17, .percent elongation at break and -modulus of elasticity are statistically unaffected by P111 treatment.
The thickness of the modified region (for these samples. estimated at. less Inn) relative to the thickness of the unmodified region for these samples estimated at around 30,000-nm) can be used to explain why Plif modification of PELiAX films -does not lead to significant changes in the mechanical properties tested of those films.
Surface Hardness of PEBAXP Films After PIII Treatment and Scratch Testing 16 Referring to FIG 21, a load curve for a silicon .plate is used as reference, and shows -typical deformation behavior of a cantilever on hard surface..
Note.that the slope of the curve is relatively steep (indicating a high modulus of elasticity) and little or no hysteresis occurs. In contrast, the load curve for untreated PEI3AX 7033 -film is not as steep (indicating a low modulus-of elasticity) and shows sigcant hysteresis. Initially, the PEBAX1 load curve goes lower, corresponding to deformation of the polymeric material under tip load, The unload curve corresponds to retrace movement of the tip, and sincethe load and unload curve are not identical, hysteresis is observed. likysteresis is caused by mech.anical energy loss due to tnovement and conformational transitions of polymer macrom.olecules under the load.
26 Such behavior is typical of relatively soft materials.
Refetring now to FIG 22, which is a load curve fbr a PEBAX* 7033 plate treated with Pill at a dose of 1.016 ionstem2 and 30 keV Note that the curve is generally steeper than the untreated plate curve shown in FIG 21, and the hysteresis has nearly disappeared. Such is curve is similar to the silicon reference curve, and is indicative that the PEBA.X4 plate has a hard surthee.
Referring to FIGS, 23 and 24, at relatively low doses, the load curve for "
treated PAX''= plates are more comOcx. Generally, there are two part i4 to these load, chives: The first part has steep curve, corresponding to a high MOdtall$, while the second part of the, atityp is pot ::as Am., corresponding to a lower moduli:1s. The' Observed comPlex character of the: load clime is believed to be caused by penetTation of the ADA tip through carbdnized region. At relatively low doses, this layer is not hard and thick enough to stop penetration by the tip.
FIG 25 Shows the dependence of the knodtilus of elaSticity Of the two parts of the load Curves tieseribedlibove. As can be s..v.p in FIG:25, the moddlos of elasticity io of the first part initially grows, µvhile the modulus:of elasticity of tk Second part Of the load turVe rettaing relatively cost. HoweVer: at a doSe of 110th ions/ere, the curve becomes linear and:the modulus of elasticity of each part becomes equal.
It :is believed that at this dose, the carbonized layer becomes hard enough to hold the tip load.
Referring to :FIGS. IS and I the results of scratch tests are shown. Different loads are apphed to Plif3AX1' 7033 plates treated at a variety of doses at 20 keV and 30 keV (dose in box is expivsSed trnuiltiples Of 10" ion$1eni2).
No:significant :differences are found between the modified and 3,mmodifi,ed PhiõBAX4 plates, ReferringflOW to FIG 20, also no Significant differences arer found ih the 2o hardness coefficient Of untreated PERAXt. plates when: compared to treated PliI3AX*
plates at a varictyof doses at 20 keY and 30 ke'V Since the thiekness of the:modified region is very small, the scratch tester is not sensitive enotigh to measure the Changes in the modified region. It is believed that the:diamond :indenter of thescratch tester penetrates through the thin modified region.
Referring to FIG 26, the modulus of elaStieity of the msboniod rcgion :dependS on the energy of penetrating ions, with higher energies :giving a higher moduhis. An especially high :modulus WaS Obsetved for an energy of 30 keV:
Sharp increase Of the modulus after 30 keV can be cOnfteeted With -forination ofgriphitie andiOLC structures.
liomogeneitv of Surface Hardness of PEBAX1' Films After Plii Treatment As discussed above, the hardness of the modified region is a function of dose and ion -energy. For homogeneity of surface hardness, the dose should be distributed equally over an entire surface. Because-the balloons are cylinder in fc.nin, the dose distribution has angular dependence, as shown in FIG. 27. Continuous rotation of the balloons during Pill treatment would provide the most homogenous surface hardness.
ffowever, if this is not possible, turning the balloons three times. 020 degrees each time) provides a reasonable homogeneity, with only a 10 percent deviation in the surflice hardness. To prepare the balloon samples desctibed above, the. three turns method was employed.
.Another reason for surface hardness inhomogeneity is plasma variation and corresponding variations of the ion &anent near the treated surface. This effect is caused by plasma density variations in volume and the charging &ex.:A of the polymer surface during high voltage pulse. This effect can be greatly reduced by positioning an additional electrode over balloon samples. For this purpose, a metal grid was utilized that was in electrical communication with the sample holden This arrangement allows ions to pass through the grid on their way to the balloon surlitee.
Dose distribution can be mapped using UV-vis spectra from 1.11E film. Such a mapping is shown in FIG 28.
As shown in FIGS. 28 and 29, the central part of the sample holder provides a dose that does not vary by more than 10%. The size of comtral part depends on size of additional electrodes. In the case of absence of die additional electrode, the dose distribution is uncontrolled. In the saniples discussed above, the area of homogenous.
dose has a diameter of approximately 50 mm. The balloons discussed above are all -treated in the central portion of the sample holder.
Withdrawal, Burst. Torque and Securement for Unmodified and Modified Balloons 'fbe table below provides data for balloon withdrawal, burst, torque and securement for unmodified and modified balloons. 'Me modified balloons are treated with Mlles described above using a dose of I0 ions/en-112 at 30 keV.
BALLOON PROPERTY UNMODIFIED MODIFIED BALLOON
Balloon Withdrawal Force 115 grams 81 grams Average Burst Pressure 293 PSI 294 PSI
Torque 1.07 N(mm) 1.26 N(mm) Securement 0.50 LB 0.96 LB
Balloon, withdrawal force Is measured using the method outlined by Devens, published U.S. Patent Application Publication No. 2004/0210211. Briefly, balloon withdrawal force is measured by determining the force required to remove a balloon from a torturous path defined by a polymer tube. Forces on the catheter and the tube can be measured by a series of transducers, as described by Devens. Torque is measured by turning the balloon in the same torturous path as used tor the balloon withdrawal force test, and determining the resistance to rotation. Average burst strength is measured by determining an inflation pressure at which the balloon bursts at 20 C, US described in Wang, U.S. Patent No. 6,171,278, and Levy, U.S.
Patent No. 4,490,421. Securement is measured using ASTM F2393-04.
In embodiments, the balloons can be used in various vascular or nonvascular applications. Exemplary applications include neuro, carotid, esophageal, or ureteral.
After treatment as described above, the balloon cars be further processed, e.g., to include a further coating, e.g., a hydro gel, or a polymer matrix coating including a drug. In embodiments, a balloon can be treated with a drug, or a polymer matrix that includes a drug, and subsequently treated by ions to modify the drug, the matrix and/or underlying balloon. Such a treatment can enhance or retard release of the drug from the balloon. In embodiments, other medical devices, e.g., coextruded medical devices, such as coextruded shafts, are treated by ions, as described above.
Still further embodiments arc in the following claims.
Claims (19)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A medical balloon, comprising:
a balloon wall comprising a base polymer material, the base polymer material comprising an integral modified region of crosslinked base polymer material and carbonized base polymer material, the crosslinked region is directly bonded to the carbonized base polymer material and to substantially unmodified base polymer material, and wherein the crosslinked region is thicker than the carbonized region, the integral modified region having a surface with a fractured surface morphology such that non-fractured islands defined by fracture lines in the surface and said non-fractured islands have an area not more than about 20 µm'.
a balloon wall comprising a base polymer material, the base polymer material comprising an integral modified region of crosslinked base polymer material and carbonized base polymer material, the crosslinked region is directly bonded to the carbonized base polymer material and to substantially unmodified base polymer material, and wherein the crosslinked region is thicker than the carbonized region, the integral modified region having a surface with a fractured surface morphology such that non-fractured islands defined by fracture lines in the surface and said non-fractured islands have an area not more than about 20 µm'.
2. The medical balloon of claim 1, wherein the carbonized region includes diamond-like material.
3. The medical balloon of claim 1, wherein the carbonized region includes graphitic material.
4. The medical balloon of claim 1, wherein the crosslinked region is directly bonded to the carbonized base polymer material and to substantially unmodified base polymer material.
5. The medical balloon of claim 1, including a region of oxidized base polymer material, the oxidized region being directly bonded to the carbonized material without further bonding to the base polymer system.
6. The medical balloon of claim 1, wherein the modified region extends from an exposed surface of the base polymer system.
7. The medical balloon of claim 1, wherein the modulus of elasticity of the base polymer system is within about +/-10% of the base polymer system without the modified region.
8. The medical balloon of claim 1, wherein the thickness of the modified region is about 10 to about 200 nm.
9. The medial balloon of claim 1, wherein the modified region is about 1%
or less of the overall thickness of the base polymer system.
or less of the overall thickness of the base polymer system.
10. The medial balloon of claim 1, wherein a, hardness coefficient of the carbonized base polymer material is about 500 Vickers Hardness (kgf/mm2) or more.
11. The medial balloon of claim 1, wherein the balloon has a fractured surface morphology having a surface fracture density of about five percent or more.
12. The medical balloon of claim 1, wherein the base polymer system carries a therapeutic agent.
13. The medical balloon of claim 1, wherein the base polymer system includes coextruded polymer layers.
14. The balloon of claim 1, wherein a compliancy of the balloon is less than 10 percent of an initial diameter of the balloon between an internal pressure from about 2 bar to about 15 bar.
15. A balloon catheter, comprising:
a balloon wall comprising a base polymer material, the base polymer material comprising an integral modified region of carbonized base polymer material, wherein the modified region includes a region of crosslinked base polymer material.
a balloon wall comprising a base polymer material, the base polymer material comprising an integral modified region of carbonized base polymer material, wherein the modified region includes a region of crosslinked base polymer material.
16. The balloon catheter of claim 15, wherein the balloon catheter is sized for use in the vascular system.
17. The balloon catheter of claim 16, wherein the balloon catheter is sized for use in the coronary arteries.
18. The balloon catheter of claim 15, wherein the balloon catheter includes a stent positioned over the balloon.
19. A balloon catheter, comprising:
a balloon wall comprising a base polymer material, the base polymer material comprising an integral modified region of crosslinked base polymer material and carbonized base polymer material, the crosslinked region is directly bonded to the carbonized base polymer material and to substantially unmodified base polymer material, and wherein the crosslinked region is thicker than the carbonized region, the integral modified region having a surface with a fractured surface morphology such that non-fractured islands defined by fracture lines in the surface and said non-fractured islands have an area not more than about 20 µm2.
a balloon wall comprising a base polymer material, the base polymer material comprising an integral modified region of crosslinked base polymer material and carbonized base polymer material, the crosslinked region is directly bonded to the carbonized base polymer material and to substantially unmodified base polymer material, and wherein the crosslinked region is thicker than the carbonized region, the integral modified region having a surface with a fractured surface morphology such that non-fractured islands defined by fracture lines in the surface and said non-fractured islands have an area not more than about 20 µm2.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11/355,392 US9526814B2 (en) | 2006-02-16 | 2006-02-16 | Medical balloons and methods of making the same |
| US11/355,392 | 2006-02-16 | ||
| PCT/US2007/062042 WO2007098330A2 (en) | 2006-02-16 | 2007-02-13 | Medical balloons and methods of making the same |
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| CA2642723A1 CA2642723A1 (en) | 2007-08-30 |
| CA2642723C true CA2642723C (en) | 2015-05-12 |
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| CA2642723A Expired - Fee Related CA2642723C (en) | 2006-02-16 | 2007-02-13 | Medical balloons and methods of making the same |
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| US (1) | US9526814B2 (en) |
| EP (1) | EP1986710B1 (en) |
| JP (1) | JP5479743B2 (en) |
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2006
- 2006-02-16 US US11/355,392 patent/US9526814B2/en not_active Expired - Fee Related
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2007
- 2007-02-13 JP JP2008555453A patent/JP5479743B2/en active Active
- 2007-02-13 AT AT07756909T patent/ATE519508T1/en not_active IP Right Cessation
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- 2007-02-13 WO PCT/US2007/062042 patent/WO2007098330A2/en active Application Filing
- 2007-02-13 EP EP07756909A patent/EP1986710B1/en active Active
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|---|---|
| ATE519508T1 (en) | 2011-08-15 |
| JP2009527283A (en) | 2009-07-30 |
| WO2007098330A3 (en) | 2008-07-17 |
| JP5479743B2 (en) | 2014-04-23 |
| WO2007098330A2 (en) | 2007-08-30 |
| US9526814B2 (en) | 2016-12-27 |
| CA2642723A1 (en) | 2007-08-30 |
| EP1986710B1 (en) | 2011-08-10 |
| EP1986710A2 (en) | 2008-11-05 |
| US20070191923A1 (en) | 2007-08-16 |
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