Subject of invention: Thrombosis resistant mechanical prosthetic heart valve

Technical background of invention

Medical equipment using Nano technology

Technical problem & objectives of invention

Inventing surgery method to replace mechanical prosthetic heart valve since 1960s resulted in significant improvement of patients' outcome suffering from heart valve disorders. Annually, about 280,000 patients undergo heart valve replacement surgery all over the world. In spite of significant improvement of prognosis, these patients now face another problem, i.e. prosthetic heart valve disorders related to its durability, and thrombosis formation. It requires careful selection of patients, medical treatment, and appropriate follow-up to prevent its potential complications. Thromboembolic event is one of the most important complications of mechanical heart valves. It may be manifested as thrombosis (figure 1) and result in obstruction or severe insufficiency of the valve or even systemic emboli (mainly cerebral). The risk of thromboembolic events increases within three first months after surgery, replacement of mitral valve, and other risk factors of thromboembolism (atrial fibrillation, left ventricular dysfunction, left atrial enlargement, and past history of thromboembolism). For this reason, all patients with mechanical valves have to take anticoagulants mainly Warfarin all over their life. Desired INR limit varies in these patients and it should be considered in prescribing medicine. However, it is not easy considering severe food and medicinal interactions in decrease or increase of warfarin effect, unpredictability of its effect from one person to another and even in different times in one person, and severe variation of INR. Then increase of INR may lead to hemorrhage complications including gastrointestinal, cerebral and other organs. Additionally, its decrease provides conditions for thromboembolic complications and patient's life is threatened in both cases. Therefore, continuous changes of INR serves as the strongest independent predictor of low survival rate in patients with mechanical heart valve so patients with prosthetic valve should undergo frequent blood tests at least once a month in order to determine dosage of warfarin. In spite of careful follow-up, desired control is not achieved in most cases.

The present invention aims at making mechanical heart valves using Nano technology through adding Nano-materials of Ti0 ₂ and Si0 ₂ or ZnO to all surfaces of mechanical valve including leaflets and their surrounding ring. Creating superhydrophobia, establishing negative charge and creating Nanowire pattern, it significantly decreases the time and area of contact between valve surfaces and blood cells, platelets and protein molecules which prevents their accumulation on the different parts of the valve such as leaflets and valve ring, subsequently nor thrombosis and neither its severe mentioned complications are occurred therefore there will be no need to prescribe anticoagulant (warfarin).

If there is not required to take warfarin, the most important cause of mortality of patients with prosthetic valve disappears and exorbitant costs spent to treat and follow up hemorrhage and thromboembolic complications of these patients decrease significantly.

A description of former technical knowledge

The first prosthetic valve replacement surgery (caged ball valve) was successfully done in 1960. Afterwards, different kinds of prosthetic valves have been invented and classified in two mechanical and biological categories (figure 2).

Caged ball valve is no longer used but the other two types are still used. Bileaflet mechanical valve is the most applicable prosthetic valve. Appropriate prosthetic valve is selected for every patient considering different factors.

Biological valves do not require long-term treatment with anticoagulants. In comparison with mechanical ones, however, they are less durable and used in older-than-65-years patients, women in reproductive ages, patients with lower life expectancy, and when it is not possible to establish appropriate level of anticoagulants. In the rest cases, mechanical valves are used.

Manuel T. Aloson plan, registered under No.US4935030 in 1990, claims that special design of valve leaflets in this plan results in better hemodynamic performance.

Mechanical valves No.WO2001030274 Al (2001) are of the recent innovations. They are consisted of a tubular structure surrounding mechanical valve. The leaflets are made of absorbable polymeric materials used to replace aorta valve in patients suffering from severe dilation of Valsalva sinus.

Po-Chien Lu et al (2005) designed a tricuspid mechanical valve registered under No. US6896700 B2 but not widely used in practice.

Mechanical valve with two horizontal and two vertical surfaces is the most recent design registered under No. US8470026 B2 in 2013 but has not used clinically. It is noteworthy that all of the above-mentioned designs need warfarin and thromboembolism is of the most important complication of mechanical heart valves. Suggesting solution for the mentioned technical problem along with exact, accurate, and integrated description of the invention:

Available conventional mechanical valves are made from metal and consisted of a ring and one or two leaflets (figure 3). The most important complication of these valves includes thromboembolic events in the form of valve thrombosis, its severe obstruction or insufficiency, and systemic emboli.

Using Nano technology, creating Nanowire patterns on surface of a material using Nano- materials such as Ti0 ₂ and Si0 ₂ and establishing negative charge may lead to severe superhydrophobia and significant decreases of contact time and area with other materials and considerable decrease of its adhesion. For this purpose, following measures are taken in two stages:

1. Covering all surfaces of leaflets and ring of mechanical valves using Si0 ₂ or ZnO nanowires with Electrophoretic Deposition method (or each of the Evaporation- Condensation growth, Vapor liquid solid growth, Template base synthesis, or Lithography methods): diameter of these nanowires varies from 20 to 50 nanometers (nm) and they are insulated against heat and electrical current.

2. Then, Ti0 ₂ nanowires (dimension: 30-60nm) are dressed up on the mentioned layers with a regular Nano-pattern using Electrophoretic Deposition or each of the mentioned methods such that maximum thickness of the mentioned two layers does not exceed lOOnm. (figure 4)

Presence of this Nano pattern results in forming of two kinds of barrier at Nano scale (10 ^~9 ) in order to prevent thrombosis at the surface of leaflets or ring. Non-conductivity of silicon or ZnO Nanowires creates an electrical barrier in all surfaces of different parts of mechanical valve through accumulation of negative charge at Nano pattern surface. Since protein molecules of coagulation factors and wall of blood cells have negative charges too, they repel each other so they will not adhere and accumulate which is mandatory to thrombosis formation.

Arrangement of Ti0 ₂ Nano-material (dimensions: 30-60 nm) which is very less than the smallest blood cell, i.e. platelet with average diameter of 2.8 micrometers (about 65 times smaller), significantly decreases contact time and area available for platelets and other blood cells as well as big protein molecules and surfaces of the mechanical valve through creating a mechanical barrier. Thus, both mechanical and electrical barriers found on the outermost layer of all surfaces of the mechanical prosthetic valve practically prevents from adhesion and accumulation of blood cells (such as platelets and blood red cells) and coagulation proteins (such as fibrin)therefore thrombosis, clots, and its embolic complications do not occur.

Advantages of invention in detail

a. Preventing from accumulation and adhesion of blood cells (platelets, red and white blood cells) and protein molecules (including fibrin strands) in all surfaces of mechanical valve which are in direct contact with blood is the most important advantage of this plan. It prevents formation of clot or thrombosis on all surfaces of mechanical prosthetic valve. b. It prevents from thromboembolic events in patients with prosthetic valve (including thrombosis formation on valve leading to its severe stenosis or insufficiency, and systemic emboli (mainly cerebral).

c. Precluding thromboembolic events, the patients with mechanical valves will not be required to use lifelong anticoagulants such as warfarin.

d. Eliminating the need to take anticoagulants such as warfarin, most problems related to adjustment of desired INR, repetitive tests, and continuous variations of INR are also resolved.

e. Eliminating the need to take anticoagulants significantly decreases complications such as life-threating hemorrhages (gastrointestinal bleeding, retroperitoneal, epistaxis, and etc.) and hospitalizations and prevents from frequent INR discrepancies, (as already renowned as the most important independent predictor of mortality in patients with prosthetic valves)

f. Significant decrease of infection of prosthesis due to preventing from accumulation, adhesion, and colonization of bacteria on surfaces of prosthetic valve.

g. The above-mentioned factors lead to significant decrease of valve destruction and dysfunction such as its stenosis or insufficiency, hospitalization, mortality rate, and increase of durability of mechanical prosthetic valve and survival rate

h. Significant decrease of treatment costs of these patients and improvement of state treatment economy through decreasing of the mentioned complications and eliminating the need to conduct repetitive tests and hospitalization. Explaining at least one practical method to use the invention

The invention may be ideally used in following cases:

All patients requiring prosthetic valve because of severe stenosis or insufficiency of the valve or destruction of the valve due to infection (endocarditis)

Since these valves do not require anticoagulants, they may be used in all patients who are candidate to receive bio prosthesis valves. Therefore, it will not be required to use bio valves along with all its restrictions.

Explicit explanation of industrial application of invention

Considering recent progress of Nano technology in Iran, the above-mentioned Nano-materials are currently produced in mass and with economical price. Thus, performing this plan in a high scale will lead to insignificant increase of prices for every mechanical prosthetic valve which is completely justifiable considering the above-mentioned advantages as well as significant decrease of treatment costs.