JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, FlowLine Bipore ® Heparin

JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, www.jotec.net

FlowLine Bipore® Heparin



medical device class III

FlowLine Bipore vascular graft

heparin coating of inner surface

wall thickness: 0,4 mm (thin wall) 0,7 mm (standard wall) length: 100 - 1000 mm diameter: 5 - 10 mm helical PTFE-monofilament reinforcement

Product Description



guideline:JOTEC FlowLine Bipore Heparin Xmm TW

coating not visible

shelf life: 2 years

no resterilization

nomenclature: i.e. 15TW6006S

length diameter

S: fully reinforced N: no reinforcement

FlowLine Bipore Heparin

Product Description



additional label FlowLine Bipore Heparin

Heparin

covalent bonded

Product Description



Same indications as FlowLine Bipore®

primarily in the periperal vascular region

- femoralpopliteal

- axillofemoral

- iliacoiliacal

- tibial and peroneal arteria

arteriovenous shunt prothesis in hemodialysis

Indications



same contraindications as FlowLine Bipore®

patients with hypersensitivity to heparin

HIT Type II (heparin-induced thrombocytopenia) - immunologic disease

- activation of platelets in presence of heparin

- 0,5 - 3% of patients after dosage of 20.000 IU/d

- occurence within 20 days

- decrease of platelets < 50%

- thrombosis and bleeding

Contraindications



lower incidence of HIT Type II with porcine heparin than

with bovine heparin (0.4% vs 1.6%)

dependent of applied heparin dose

Number of patients Thrombocytopenia(<50 000 / µl)

Thrombocytopenia (<100 000 / µl)

Thrombotic Complications

Full-Dose Heparin(> 20.000 IU/d)

7/981 (0,7%) 26/1080 (2,4%) 4/1080 (0,4%)

Low-Dose Heparin(< 15.000 IU/d)

0/362 (0%) 1/362 (0,3%) no

Warketing T., Kelton J., Prog Hemost Thromb 10, 1-34, 1991

Thrombocytopenia



Coating of FlowLine Bipore Heparin

heparin from porcine intestinal mucosa

release of at most 20 IU in the case of largest graft

no complications may be expected!

Thrombocytopenia



physiological coagulation inhibitor

liver, lung and intestinal mucosa

physiological blood concentration: 100 µg/l

enzymatic degradation by Heparinase

half-life: 90 – 120 min

partially excretion by urine

Heparin in General



binding of Antithrombin III in the blood plasma

inhibition of coagulation

imitation of the antithrombotic effect of heparansulfate

as in the case of the natural endothelium

creation of a „blood friendly“ surface by binding of

selected plasma proteins

Functional Principle



Name Producer Market entry Bonding Application

Carmeda BioActive Surface®

Medtronic 1985 covalent ECC, ventricular assist devices, central venous catheter, coronary stent, ePTFE vascular graft (Gore)

Duraflo II® Baxter 1988 ionic ECC

Bioline Coating®

Jostra AG 1992 covalent with ionic interaction

ECC, centrifugal pump, catheter, canules, tubes

Established Heparin Coatings



InterVascular

InterGard™ Heparin

W.L. Gore & Associates

GORE-TEX® PROPATEN Vascular Graft

JOTEC


Heparin Coating of Vascular Grafts



Product name Material Heparin Bonding Registration

InterGardTM Heparin

Polyester

Collagenporcine /

high molecular ionic 1991

GORE-TEX® Propaten

ePTFEporcine /

low molecularcovalent 2002


ePTFEporcine /

high molecular

covalent with ionic interaction

2003

Product Comparison



InterGard™ Heparin

Polyester Collagen Heparin + Adhesive agent

GORE-TEX® PROPATEN

ePTFE

HeparinAdhesive agent

Activated

surface

FlowLine Bipore® HeparinHeparin

Adhesive agent ePTFE

Structural Comparison



ePTFE

Adhesive agent

Heparin

Covalent bonding

+

–

FlowLine Bipore® Heparin – Coating



InterGard™ Heparin – Coating

ionic binding of high molecular heparin to polyester

TDMAC (Tridodecyl-methyl-ammoniumchloride) as

adhesive agent

impregnation of heparinized polyester graft with

collagen


FlowLine Bipore® HeparinInterGard™ Heparin

Just a fractional amount of heparin in contact with blood after implantation!


FlowLine Bipore® HeparinInterGard™ Heparin

in vitro stability of heparin coating over 4 weeks with minimal loss after 7 days

prospektive randomized clinical trial in comparison to

uncoated ePTFE vascular graft

(Devine et al.J Vasc Surg 2001)

• lower amputation rate (6 vs 17)

• significantly higher patency rates


FlowLine Bipore® HeparinInterGard™ Heparin – Randomized Clinical Trial

Product brochure InterGard Heparin P/N: 7366/2


FlowLine Bipore® HeparinGORE-TEX® PROPATEN Vascular Graft – Coating

heparin coating of ePTFE vascular grafts

• surface activation

• application of adhesive agent

• covalent binding of low molecular heparin by end-point attachment

interaction of active heparin sequences with circulating blood


FlowLine Bipore® HeparinGORE-TEX® PROPATEN Vascular Graft

stability proven in vitro – marginal heparin release within

24 h

improved patency rates after 6 months ( Fig. 1)

• Test animal: dog

• Implantation site: Arteria carotis shunt model

• Ø: 3mm, length: no statement

no thrombus formation on bioactive surface after

implantation for 2 h ( Fig. 2)


FlowLine Bipore® HeparinFlowLine Bipore® Heparin – Coating

alternating coating consisting of adhesive agent and high molecular heparin high heparin loading to the inner surface!

synthetic protein as adhesive agentavoidance of toxic substances!

covalent cross linking by EDC (carbodiimide) avoidance of toxic substances!

covalent bonding and ionic interactions bioactive sequences freely accessible!

stable bonding of heparin!



FlowLine Bipore® Heparin – Coating

no effect on the graft handling

• implantation technique

• anticoagulation

no modification of mechanical features of ePTFE graft



H.P. Wendel Clinical Research Laboratory, Dept. of Thoracic and Cardiovascular Surgery, University of Tübingen

Dynamic Blood Test Using a Chandler Loop Model

37 °C

ePTFE graftØ: 6 mm, l: 50 cm

blood: 18 mlheparin: 1,2 IU/mlcontact time: 2h

37 °C



Platelets [x103/µl]

C P H C P H C P H

C: ControlP: ePTFE graft

H: FlowLine Bipore®

Heparin

Dynamic Blood Test Using a Chandler Loop Model


FlowLine Bipore® HeparinDynamic Blood Test Using a Chandler Loop Model

ePTFE graft after 2 hours of blood contact

FlowLine Bipore® Heparin after 2 hours of blood contact


FlowLine Bipore® HeparinComparison of Product Range JOTEC vs GORE-TEX

JOTEC Thin Wall, w/o reinforcement

Gore Thin Wall, w/o reinforcement

Length [cm] Ø [mm] Catalogue-No.

40 5 15TW4005N not available

50 678

15TW5006N15TW5007N15TW5008N

6not available

8

80 678

15TW8006N15TW8007N15TW8008N

6not available

8


FlowLine Bipore® HeparinComparison of Product Range JOTEC vs GORE-TEX

JOTEC Thin Wall, reinforced Gore Thin Wall, reinforced

Length [cm] Ø [mm] Catalogue-No.

40 5 15TW4005S not available

50678

15TW5006S15TW5007S15TW5008S

not availablenot availablenot available

70 5 15TW7005Snot available

6

80678

15TW8006S15TW8007S15TW8008S

6not available

8



Thin Wall Standard Wall

w/oreinforcement reinforced w/o reinforcement reinforced

L [cm] Ø [mm] L [cm] Ø [mm] L [cm] Ø [mm] L [cm] Ø [mm]

10 5 10 5 2067

40 5 40 5 40 5 - -

50678

50 678

50678

50678

70 5 70 5 70 5 - -

80678

80678

- - 80678

JOTEC Product Range



Product Advantages

coating of inner surface

no toxic substances

stable covalent binding of heparin

bioactive heparin sequences freely accessible

high permanent hemocompatibility

widest product spectrum


FlowLine Bipore® HeparinGORE-TEX® PROPATEN Vascular Graft

Product brochure GORE-TEX PROPATEN June 2002

Fig. 1



GORE-TEX® PROPATEN Vascular Graft

Product brochure GORE-TEX PROPATEN June 2002

Fig. 2

Documents

JOTEC GmbH, Lotzenäcker 23, 72379 Hechingen, Germany, FlowLine Bipore ® Heparin