patent ductus arteriosus occlusion device david brogan *, darci phillips *, daniel schultz *, dr....

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Patent Ductus Arteriosus Occlusion Device David Brogan * , Darci Phillips * , Daniel Schultz * , Dr. Thomas Doyle * Vanderbilt University Biomedical Engineering Department Vanderbilt University Medical Center, Pediatric Cardiology Abstract Patent ductus arteriosus is the persistence after birth of an in-utero shunt from the pulmonary artery to the aorta. To correct this deficiency, an elective procedure is performed at five to ten years of age to close the hole. Current treatment involves catheter insertion of fibrous coils into the duct, relying on endothelialization to completely occlude flow. This project sought to build on two previous groups efforts to design an alternative closure device. Biocompatible materials were investigated, a prototype built, and tests performed to measure the effectiveness of the design. A polymer specialty firm was contacted to make a certified prototype and preliminary work has been completed in the application for a patent. Introduction Objectives It was determined that the Patent Ductus Arteriosus Occlusion Device must meet the following conditions: •Made from biocompatible materials •Conforms to the shape of the PDA and causes occlusion •Be delivered via a catheter <2mm in diameter (6-7F) •Provide an initial success rate of 100% •Quick endotheliazation (~1 month) •Can be easily repositioned •Cost effective (<$200) •Simple implantation system •More patient friendly Patent ductus arteriosus (PDA) is the persistence of a normal fetal structure between the left pulmonary artery and the descending aorta. Persistence of this fetal structure beyond 18 days of life is considered abnormal. This condition accounts for 10-12% of all congenital defects and has an estimated incidence of more than 20,000 cases in the United States alone. It is responsible for many adverse effects including growth retardation, breathlessness, lack of appetite, bacterial endocarditis, and congestive heart failure. Multiple treatments have been developed for PDA, including drug therapy (indomethacin), invasive surgical ligation and transcatheter implantable devices. The most common devices used to date are the Cook Coils and the Amplatzer Duct Occluder (ADO) (Figs. 1 & 2). A major disadvantage of these methods is being thick and rigid, forcing the PDA to conform to their shape, causing undesirable stress and tension on the walls of the PDA. Thus, the demand remains for a cost-effective device that can be delivered through a small catheter and successfully occlude the PDA. Fig. 2 Cook Coil Fig. 1 Amplatzer Duct Occluder Methods Discussion & Results Conclusions Future Work and Recommendations •Work with PTG, Inc to build and manufacture device prototype of correct size, shape and biomaterials •Obtain IRB approval for animal testing of this device on canines •Work with VUMC Cardiology Department to begin animal testing •Produce finalized design drawings for patent filing and continue work with Office of Tech Transfer •Run final in vitro tests using canine blood as opposed to References Market Analysis & Patent •Market: •Children: birth – 15 years •Adults: varying in ages •Projected sales: •Year 1: $2.7 million •Year 5: $3.6 million •Selling price of PDA device: $200 •Costs of goods sold per device: •Polyurethane foam: $3.25 •Nitinol wire: $0.90 •Manufacturing costs: $12.00 •Manufacture insurance: $36.00 •Incremental cost: $85.00 Fig 3. Prototype Sketch Fig 4. Close-up of PDA Simulati on Fig 5. In Vitro Testing •Patent fees: $20,000 •In process of filing preliminary patent with Office of Technology Transfer •Dr. Paul King •Dr. Robert Galloway •John Warmath •Len Pinchuk •Brian Cox •Garson, Arthur et al. The science and practice of pediatric cardiology. Baltimore: Williams & Wilkins, 1998. pg. 1055-1069. •Refinement of this device to its current design provides much potential for successful occlusion of PDA •Using available resources, we have reached the final stages of this design process and must now resort to a third party for future development •Quality control requires a sterile building and manufacturing for actual implantation in future testing •To complete design process, third party support must be obtained for improved facilities and additional expenses Design Refinement & Tests After several brainstorming sessions and Internet searches of current occluders, a design similar to last years group was decided upon. A mushroom shaped foam would yield flexibility that could conform to PDA shapes, with a Nitinol wire backbone to infuse strength and support. Fig. 3 shows a rendering of the conceptual design decided upon at the brainstorming sessions. Two separate tests were conducted to ensure proper functioning of the device design. First, it was necessary to ensure that the foam plug could withstand a maximum pressure difference of 100 mmHg using tubing and a column of water. Second, a flow test using an in-vitro PDA simulation was conducted to determine if the device would indeed occlude the flow between the pulmonary artery and aorta. Search for Materials Several epistaxis strip producers were contacted about using their foam, with little success. Most makers of biocompatible foams will not certify their foam for use in the body, thus few commercial foams were available. A materials expert in Florida was able to outline the steps and chemicals necessary to manufacture a biocompatible foam independently. One particular chemical proved impossible to procure by students. The Nitinol memory wire was easy to secure and relatively inexpensive. Thus, for testing purposes, generic foam was used with copper wire. In-vitro testing (Fig. 4 & Fig. 5) demonstrated that water would slowly move through the device, however the flow should be minimized in the body due to the thrombogenic nature of the blood. Pressure testing also yielded promising results with the foam device. Leakage did occur, but the device was not dislodged by the pressure. Two prototypes were built, reflecting the stages of design. First, a clay model was built to determine the proportions of the materials and aid in discussions (Fig. 6). Second, a silicone device was made with a wire wrap backbone to simulate the size and structure of the final design (Fig. 7). Fig 6. Initial clay device. Fig 7. Final silicone prototype. Sales ofPD A D evice Vs.Profits 0 1,000,000 2,000,000 3,000,000 4,000,000 5,000,000 6,000,000 7,000,000 0 1 2 3 4 5 6 Tim e (Years) Dollars Sales Profits

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Page 1: Patent Ductus Arteriosus Occlusion Device David Brogan *, Darci Phillips *, Daniel Schultz *, Dr. Thomas Doyle ‡ * Vanderbilt University Biomedical Engineering

Patent Ductus Arteriosus Occlusion DeviceDavid Brogan*, Darci Phillips*, Daniel Schultz*, Dr. Thomas Doyle‡

*Vanderbilt University Biomedical Engineering Department‡Vanderbilt University Medical Center, Pediatric Cardiology

Abstract

Patent ductus arteriosus is the persistence after birth of an in-utero shunt from the pulmonary artery to the aorta. To correct this deficiency, an elective procedure is performed at five to ten years of age to close the hole. Current treatment involves catheter insertion of fibrous coils into the duct, relying on endothelialization to completely occlude flow. This project sought to build on two previous groups efforts to design an alternative closure device. Biocompatible materials were investigated, a prototype built, and tests performed to measure the effectiveness of the design. A polymer specialty firm was contacted to make a certified prototype and preliminary work has been completed in the application for a patent.

Introduction

ObjectivesIt was determined that the Patent Ductus Arteriosus Occlusion Device must meet the following conditions: •Made from biocompatible materials •Conforms to the shape of the PDA and causes occlusion•Be delivered via a catheter <2mm in diameter (6-7F)•Provide an initial success rate of 100%•Quick endotheliazation (~1 month) •Can be easily repositioned•Cost effective (<$200)•Simple implantation system •More patient friendly

Patent ductus arteriosus (PDA) is the persistence of a normal fetal structure between the left pulmonary artery and the descending aorta. Persistence of this fetal structure beyond 18 days of life is considered abnormal. This condition accounts for 10-12% of all congenital defects and has an estimated incidence of more than 20,000 cases in the United States alone. It is responsible for many adverse effects including growth retardation, breathlessness, lack of appetite, bacterial endocarditis, and congestive heart failure. Multiple treatments have been developed for PDA, including drug therapy (indomethacin), invasive surgical ligation and transcatheter implantable devices. The most common devices used to date are the Cook Coils and the Amplatzer Duct Occluder (ADO) (Figs. 1 & 2). A major disadvantage of these methods is being thick and rigid, forcing the PDA to conform to their shape, causing undesirable stress and tension on the walls of the PDA. Thus, the demand remains for a cost-effective device that can be delivered through a small catheter and successfully occlude the PDA.

Fig. 2 Cook CoilFig. 1 Amplatzer Duct Occluder

Methods

Discussion & Results

Conclusions

Future Work and Recommendations

•Work with PTG, Inc to build and manufacture device prototype of correct size, shape and biomaterials•Obtain IRB approval for animal testing of this device on canines •Work with VUMC Cardiology Department to begin animal testing•Produce finalized design drawings for patent filing and continue work with Office of Tech Transfer •Run final in vitro tests using canine blood as opposed to water •Continue to refine design based upon strength and durability test results

References

Market Analysis & Patent•Market:

•Children: birth – 15 years•Adults: varying in ages

•Projected sales: •Year 1: $2.7 million•Year 5: $3.6 million

•Selling price of PDA device: $200•Costs of goods sold per device:

•Polyurethane foam: $3.25•Nitinol wire: $0.90•Manufacturing costs: $12.00•Manufacture insurance: $36.00•Incremental cost: $85.00

Fig 3. Prototype Sketch

Fig 4.

Close-up

of PDA

Simulation

Fig 5.

In Vitro Testing

•Patent fees: $20,000•In process of filing preliminary patent with Office of Technology Transfer

•Dr. Paul King•Dr. Robert Galloway •John Warmath •Len Pinchuk •Brian Cox

•Garson, Arthur et al. The science and practice of pediatric cardiology. Baltimore: Williams & Wilkins, 1998. pg. 1055-1069.

•Refinement of this device to its current design provides much potential for successful occlusion of PDA•Using available resources, we have reached the final stages of this design process and must now resort to a third party for future development•Quality control requires a sterile building and manufacturing for actual implantation in future testing •To complete design process, third party support must be obtained for improved facilities and additional expenses

Design Refinement & TestsAfter several brainstorming sessions and Internet searches of current occluders, a design similar to last years group was decided upon. A mushroom shaped foam would yield flexibility that could conform to PDA shapes, with a Nitinol wire backbone to infuse strength and support. Fig. 3 shows a rendering of the conceptual design decided upon at the brainstorming sessions.Two separate tests were conducted to ensure proper functioning of the device design. First, it was necessary to ensure that the foam plug could withstand a maximum pressure difference of 100 mmHg using tubing and a column of water. Second, a flow test using an in-vitro PDA simulation was conducted to determine if the device would indeed occlude the flow between the pulmonary artery and aorta.

Search for MaterialsSeveral epistaxis strip producers were contacted about using their foam, with little success. Most makers of biocompatible foams will not certify their foam for use in the body, thus few commercial foams were available. A materials expert in Florida was able to outline the steps and chemicals necessary to manufacture a biocompatible foam independently. One particular chemical proved impossible to procure by students. The Nitinol memory wire was easy to secure and relatively inexpensive. Thus, for testing purposes, generic foam was used with copper wire.

• In-vitro testing (Fig. 4 & Fig. 5) demonstrated that water would slowly move through the device, however the flow should be minimized in the body due to the thrombogenic nature of the blood.

• Pressure testing also yielded promising results with the foam device. Leakage did occur, but the device was not dislodged by the pressure.

• Two prototypes were built, reflecting the stages of design. First, a clay model was built to determine the proportions of the materials and aid in discussions (Fig. 6). Second, a silicone device was made with a wire wrap backbone to simulate the size and structure of the final design (Fig. 7).

Fig 6. Initial clay device. Fig 7. Final silicone prototype.

Sales of PDA Device Vs. Profits

0

1,000,000

2,000,000

3,000,000

4,000,000

5,000,000

6,000,000

7,000,000

0 1 2 3 4 5 6

Time (Years)

Dol

lars

Sales

Profits