Title Of Invention: A DEVICE ENHANCING THE BLOOD CIRCULATION AT THE EXTREMITI ES USI NG COMPRESSED CARBON DIOXIDE-SATURATED WATER

Technical Field

Biomedical engineering

Background Art

Diabetes mellitus

Diabetes is a chronic condition that occurs when the body cannot produce enough insulin or cannot use insulin, and is diagnosed by observing raised levels of glucose in the blood. Insulin is required to transport glucose from the bloodstream into the body's cells where it is used as energy. The lack, or ineffectiveness, of insulin in a person with diabetes means that glucose remains circulating in the blood. Over time, the resulting high levels of glucose in the blood (known as hyperglycemia) causes damage to many tissues in the body, leading to the development of disabling and life-threatening health complications[l].

Diabetes is one of the largest global health emergencies of the 21st century. Each year more and more people live with this condition, which can result in life-changing complications. In addition to the 415 million adults who are estimated to currently have diabetes, there are 318 million adults with impaired glucose tolerance, which puts them at high risk of developing the disease in the future, in 2015 One out of every eleven adults has diabetes (9.09% of world population)and the ratio will rise to one out of every ten adults in 2040 (10% of world population)[l].

In Sub-Saharan Africa contains 33 of the 50 poorest countries in the world, and this region will experience the greatest rise in the prevalence of diabetes in the next 20 years, and locally in Sudan there are over 1.4 million cases of diabetes in Sudan in 2015[2].

Diabetic foot

Diabetic foot is an infection, ulceration, or destruction of deep tissues of the foot associated with neuropathy and/or peripheral arterial disease in the lower extremity of people with diabetes[3].

People with diabetes can experience problems with poor circulation to the feet, as a result of damage to blood vessels. These problems increase the risk of ulceration, infection and amputation. People with diabetes face a risk of amputation that may be more than 25 times greater than that in people without diabetes. With good management however, a large proportion of amputations can be avoided. In view of these risks, it is important that people with diabetes examine their feet regularly[l][3][3].

The diabetes affects 15% of people with diabetes that That means 1.4% of the world's population (more than 11 million people around the world). Amputation

The end stage of the diabetic foot syndrome is the requirement for amputation as many as 6 - 10% of all patients with diabetes will undergo amputation for treatment of infection, accounting for 57% of no traumatic lower extremity amputations[4], patients with diabetes have a 15 times increased risk of amputation relative to the normal population[5].

In United States More than half of lower limb amputations occur in people with diagnosed diabetes[6], In Sudan and other developing countries, 80% - 60% of amputations due to diabetes according to the National Authority for prosthetics and Aesthetics estimates[7].

Artificial Carbon Dioxide Bath

In 1624 medical scholar van helmont confirmed that gases contain carbon dioxide. The anti- infective properties of carbon dioxide were discovered and analyze by boyel and Lavoisier. The first systematic medical research of C02 use was conducted by lalouette in 1777, who showed that chronic and invent rated skin damage cured by serial application of C02[8].

Carboxytherapy is the use of C02-rich water bathing which was developed in France in 1930. It was found that C02 helped in wound healing and fat accumulation in arteries[9].

In 1997, Hartmann et al. reported that immersion in water enriched with carbon dioxide (C02) had positive microcirculatory effects. In 2002, we demonstrated that C02 immersion increased the blood flow of feet to the much higher extent than the plain water, and it improved the limb salvage rate in CLI patients without revascularization option[10]

Carbon dioxide is easily absorbed percutaneously. Consequently, it is inherently the end product of metabolism, can be artificially increased in the tissues by absorbing carbon dioxide percutaneously from a carbonated water bath. As a result, blood vessels can be dilated and blood flow volume can be increased. As a result of this action, blood vessels are temporarily dilated. Alternatively, dysfunctional finer vessels can be opened again to increase blood flow volume or allow blood to enter peripheral tissues. This technique for alleviating symptoms is actively used in the form of carbonated springs therapy[ll]

Artificial C02-enriched water has been prepared by various methods, for example by dissolving tablets containing sodium bicarbonate and succinic acid in hot fresh water or by bubbling C02 gas into ordinary bath water[12] Or through mechanical pressure as in the manufacture of soft drinks.

In one study One hundred patient with diabetic foot attend to Alnajaf endocrine and diabetic center treated by CAR BOTH ERA device [11] ( C02 water bath therapy ), 60 female and 40 male with averageage50 year ,The result 65% of patient healed and 35% have partial response to treatment or recurrence after cure of same lesion or recurrence in another area of foot[8].

Carbon Dioxide Therapy (CDT)

Carbon dioxide (C02) therapy refers to the transcutaneous or subcutaneous administration of C02 for therapeutic purposes. One example of this is the use of spa therapy that emerged as an important treatment in Europe during the 1800s, another example is the use of artificial C02 enriched water for bathing, which has been clinically applied to improve ischemic limb symptom. These therapeutic effects of C02 are caused by an increase in blood flow and microcirculation assessed by Laser Doppler, and an increase of tcP02 in ischemic tissues, which is explained by the Bohr effect[13].

At international conference in Freibourg-en-Brisgau (1989) a consensus summarizing the effects of Carboxytherapy that increase of local blood supply by opening of functionally closed capillaries and by dilatation of precapillary segments (the vascularization therapy), improvement of oxygenation by increased release of oxygen from hemoglobin (Bohr ^' s effect - in lower pH and higher pC02 - partial pressure of C02- hemoglobin ^' s affinity to oxygen is decreased), increase of erythrocytes ^' deformability and antiseptic effect[14].

Vascularization therapy

A vascularization therapy that increases the number of newly formed blood vessels of an affected site by immersing in carbonated warm water having a carbon dioxide concentration of 700 ppm or more and a water temperature of 33 to 42° C[ll].

A vascularization therapy that increases the number of vascular endothelial cells in tissue of an affected site by 1.5 times or more and that increases the number of endothelial precursor cells in the peripheral blood at an affected site by 1.1 times or more by immersing the affected site of a peripheral blood vessel in the aforementioned carbonated warm water[ll]

Bohr effect

For hemoglobin to carry the required oxygen molecules to cells from the lungs, hemoglobin carries two final products of cellular respiration H+ and C02 from the tissues to the lungs and kidneys, The C02 produced by oxidation of organic fuels in mitochondria, is hydrated to form bicarbonate:

C02 + H20 = H+ + HC03- (1)

This reaction is catalyzed by carbonic anhydrase, an enzyme particularly abundant in erythrocytes. Carbon dioxide is not very soluble in aqueous solution, and bubbles of C02 would form in the tissues and blood if it were not converted to bicarbonate. As you can see from the reaction catalyzed by carbonic anhydrase, the hydration of C02 results in an increase in the H+ concentration (a decrease in pH) in the tissues. The binding of oxygen by hemoglobin is profoundly influenced by pH and C02 concentration, so the inter conversion of C02 and bicarbonate is of great importance to the regulation of oxygen binding and release in the blood [15].

The binding of H+ and C02 is inversely related to the binding of oxygen. At the relatively low pH and high C02 concentration of peripheral tissues, the affinity of hemoglobin for oxygen decreases as Hland C02 are bound, and 02 is released to the tissues. Conversely, in the capillaries of the lung, as C02 is excreted and the blood pH consequently, rises, the affinity of hemoglobin for oxygen increases and the protein binds more 02 for transport to the peripheral tissues. This effect of pH and C02 concentration on the binding and release of oxygen by hemoglobin is called the Bohr effect, after Christian Bohr, the Danish physiologist (and father of physicist Niels Bohr) who discovered it in 1904[15].

The binding equilibrium for hemoglobin and one molecule of oxygen can be designated by the reaction:

Hb + 02 = Hb02 (2) but this is not a complete statement. To account for the effect of H+ concentration on this binding equilibrium, we rewrite the reaction as:

HHb+ + 02 = Hb02 + H+ (3) where HHb+ denotes a protonated form of hemoglobin. This equation tells us that the 02- saturation curve of hemoglobin is influenced by the H+ concentration.

Both 02 and H+ are bound by hemoglobin, but with inverse affinity. When the oxygen concentration is high, as in the lungs, hemoglobin binds 02 and releases protons. When the oxygen concentration is low, as in the peripheral tissues, H+ is bound and 02 is released.

The pH of blood is 7.6 in the lungs and 7.2 in the tissues. Experimental measurements on hemoglobin binding are often performed at pH 7.4 as in the figure 3 in the drawings file[15].

Thus we see that the four polypeptide chains of hemoglobin communicate with each other not only about 02 binding to their heme groups but also about H+ binding to specific amino acid residues. And there is still more to the story. Hemoglobin also binds C02, again in a manner inversely related to the binding of oxygen. Carbon dioxide binds as a carbonate group to thect- amino group at the amino-terminal end of each globin chain, forming Carbaminohemoglobin.

This reaction produces H+, contributing to the Bohr effect. When the concentration of carbon dioxide is high, as in peripheral tissues, some C02 binds to hemoglobin and the affinity for 02 decreases, causing its release. Conversely, when hemoglobin reaches the lungs, the high oxygen concentration promotes binding of 02 and release of C02. It is the capacity to communicate ligand-binding information from one polypeptide subunit to the others that makes the hemoglobin molecule so beautifully adapted to integrating the transport of 02, C02, and H+ by erythrocytes[15].

The optimal Therapeutic conditions

The CDT required carbonated warm water having a carbon dioxide concentration higher than700 ppm and a water temperature of 33 to 42° C (more preferably from 35 to 39° C near body temperature).

If the water temperature is lower than 33° C, vascularization action is unable to be adequately obtained, and it becomes difficult to immerse the affected area for the required amount of time since the carbonated water feels cold to the patient. And if the water temperature is higher than 42° C, metabolism is accelerated excessively which has a detrimental effect on tissue regeneration, while also making it difficult to immerse the affected area for the required amount of time since the carbonated water feels hot to the patient. The amount of carbon dioxide percutaneous absorption from a carbonated warm water bath increases proportionately to the concentration of carbon dioxide dissolved in the carbonated warm water. The frequency of immersion is preferably at least once every 24 hours. Moreover, if the frequency of immersion is from 1 to 2 times every 24 hours, adequate effects are obtained and the load on the patient is not excessively large, thereby making this preferable[ll].

In order to allow the action of the carbon dioxide to reach deeper, the immersion time of a single treatment is preferably at least 10 minutes. Moreover, if the duration of a single immersion is within the range of 10 to 30 minutes, adequate effects are obtained and the burden on the patient is not excessively large[ll].

The CDT performed by the highly concentrated carbonated warm water is associated with a high degree of safety, and can be performed easily without requiring any special complicated apparatuses or equipment[ll].

In order to achieve the maximum benefit of carbon dioxide therapeutic effect; a Hydro-thermo- Mechanical system has been designed to deliver a carbon dioxide saturated water with a concentration higher than 700 parts per million, a temperature between 35-39 ° C and applied contact pressure between the solution and the surface of the skin around 100 millimeters of mercury.

Technical Problem

In spite of the effectiveness of carboxytherapy, the shortage of tools and techniques stands in the way of relying on it as a proper method of preventing and healing blood circulation issues and diabetic foot ulcers.

The prior technology and tools of carboxytherapy focuses on the production of the C02 saturated water instead of focusing on the therapy operation itself (the transcutaneous absorption of C02 for therapeutic purposes).

Solution to Problem

To get the maximum effectiveness of carboxytherapy, our invented system works on compressing the C02 saturated water on the skin to increase both the amount of absorbed gas and the bohr effect to enhance the blood flow and circulation in the extremities and heal diabetic foot ulcers.

Summary of Invention

The effectiveness of the therapy can also be greatly increased by compressing the C02 saturated water on the skin of the extremities which will increase the amount of transcutaneous absorbed gas, in turn increasing the positive effect on the blood circulation according to the bohr effect law (as explained in the background).

Our invented system works on compressing the C02 saturated water on the skin to increase both the amount of absorbed gas and the bohr effect to enhance the blood flow and circulation in the extremities and heal diabetic foot ulcers. summarized description of invention

(A DEVICE ENHANCING THE BLOOD CIRCULATION AT THE EXTREMITIES USING COMPRESSED CARBON DIOXIDE-SATURATED WATER).

Compresses the C02 saturated water on the skin which increases the amount of absorbed gas and enhances the blood flow and circulation according to the bohr effect as shown in figure 3. Figures 1 and 2 show the simple system mechanism which depends on the compression of C02 saturated water on the skin either by an external air inflatable membrane as shown in figure 1, or by pumping a suitable amount of C02 saturated water in the enclosed environment of the system which in turn compresses the fluid on the skin as shown in Figure 2. Advantageous Effects of Invention

The system will be used by both diabetic patients who already has diabetic foot ulcers for therapeutic purposes, and diabetic patients who doesn't have diabetic foot issues for preventive purposes.

The system can also be used as a physiotherapy to enhance blood circulation for people who has blood flow issues.

Brief Description of Drawings

The drawings file contains three illustrative figures.

Figure 1

The figure shows the systems mechanism in case of depending on applying extra pressure on the fluid and the extremity together.

Figure 2

Shows the systems mechanism in case of depending only on the fluids pressure inside the closed chamber including the skin of the effected limb.

The next table shows the main components in the figures pointed out with numbers:

figure 3

explains how hydrogen ions and carbon dioxide affect the affinity of oxygen in Hemoglobin (bohr effect). Detailed description

A device enhancing the blood circulation at the extremities using compressed C02 saturated water.

The system works on compressing the carbon dioxide saturated water on the skin of the body which increases the absorbability of the gas and enhance the blood circulation according to the Bohr effects shown in figure 3. Figures 1 and 2 show the simple system mechanism which depends on the compression of C02 saturated water on the skin either by an external air inflatable membrane as shown in figure 1, or by pumping a suitable amount of C02 saturated water in the enclosed environment of the system which in turn compresses the fluid on the skin as shown in Figure 2.

The invention consists of two main units:

1- carbon dioxide saturated water production unit, which is responsible for the compressing of the gas and it's dissolving, and controlling its temperature.

It's a separate unit to provide the fluid in the required chemical and physical conditions.

After preparing the fluid, this unit transfers it to the second unit (containment and compression unit through the carbon dioxide saturated water inlet shown as element number 9 in the attached figures.

2- containment and compression unit: shown in figure 1 and figure 2, it consists of a plastic bag shown as element number 5 in the figures, connected to a carbon dioxide saturated water inlet shown as element 9, the bag contains the carbon dioxide saturated water (element 4) and the patient inserts the affected limb (element 1) inside the bag and seal it near the knee.

The bag (element 5) is surrounded by a two layers sock shaped rubber, the inner layer is inflatable (element 3) and the external layer is a hard and static (shown as element 6 in the figures).

The compressed air (shown as element 7 in the figures) is pumped between the two layers of the rubber sock. Which will get the inflatable layer (element 3) to expand and towards the plastic bag (element 5) Which will in turn compress the bag and the carbon dioxide saturated water against the skin. Compressed air will come through the inlet a shown as element 2, increasing the pressure of the fluid against the skin, and exits through the outlet shown as element 8 causing the pressure to decrease on the internal components (the plastic bag and the affected limb).

The system works in Two modes:

1- air pressure mode:

compressing the C02 saturated water on the skin depends on air compression, using less amount of the fluid as shown in (figure 1).

2- fluid pressure mode:

compressing the C02 saturated water on the skin depends on the amount of carbon dioxide saturated water compressed in the plastic bag.

As shown in figure 2 fluid pressure in limited space will lead to fluid pressure on the surface of the skin.

in this mode no air compression is used to apply external pressure, instead the pressure of the fluid itself is considered enough as shown in (figure 2).

References:

[I] F. Aguiree, A. Brown, N. H. Cho, G. Dahlquist, S. Dodd, T. Dunning, M. Hirst, C. Hwang, D.

Magliano, and C. Patterson, "IDF diabetes atlas," 2015.

[2] A. J. M. Boulton, L. Vileikyte, D. Armstrong, and I. D. Federation, "The global burden of diabetic foot disease.," Lancet (London, England), vol. 366, no. 9498, pp. 1719-24, Nov. 2005.

[3] N. Singh, D. G. Armstrong, and B. A. Lipsky, "Preventing foot ulcers in patients with diabetes.," JAMA, vol. 293, no. 2, pp. 217-28, Jan. 2005.

[4] M. G. Hochman, Y. Cheung, D. P. Brophy, and J. A. Parker, "Imaging of the Diabetic Foot," in The Diabetic Foot, Springer, 2006, pp. 227-253.

[5] E. J. G. Peters, "The infected diabetic foot," in High risk diabetic foot: treatment and prevention, 2010, pp. 92-126.

[6] N. D. D. Group, N. I. of Diabetes, Digestive, and K. Diseases, "Lower Extremity Foot Ulcers and

Amputations in Diabetes," in Diabetes in America, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney diseases, 1995.

[7] Napo, "napo estimates," 2015.

[8] SAMEER ALKHAWAJA, "CARBAL THERAPY FOR TREATMENT OF DIABETIC FOOT ( C02 WATER BATH )," Kufa Med.Journal, vol. 15, no. 1, pp. 211-222, 2012.

[9] N. Shalan, A. Al-bazzaz, I. Al-ani, F. Najem, and M. Al-masri, "Effect of Carbon Dioxide Therapy on Diabetic Foot Ulcer," J. Diabetes Mellit, no. November, pp. 284-289, 2015.

[10] H. Hayashi, S. Yamada, Y. Kumada, H. Matsuo, T. Toriyama, and H. Kawahara, "Immersing Feet in Carbon Dioxide-enriched Water Prevents Expansion and Formation of Ischemic Ulcers after Surgical Revascularization in Diabetic Patients with Critical Limb Ischemia.," Ann. Vase. Dis., vol. 1, no. 2, pp. 111-7, 2008.

[II] Hiroki Sakakibara, Ken Ooyachi, and Hiroaki Matsubara, "Vascularization therapy by highly

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[12] N. Nishimura, J. Sugenoya, T. Matsumoto, M. Kato, H. Sakakibara, T. Nishiyama, Y. Inukai, T.

Okagawa, and A. Ogata, "Effects of repeated carbon dioxide-rich water bathing on core temperature, cutaneous blood flow and thermal sensation," Eur. J. Appl. Physiol., vol. 87, no. 4-5, pp. 337-342, Jan. 2002.

[13] Y. Sakai, M. Miwa, K. Oe, T. Ueha, A. Koh, T. Niikura, T. Iwakura, S. Y. Lee, M. Tanaka, and M.

Kurosaka, "A Novel System for Transcutaneous Application of Carbon Dioxide Causing an 'Artificial Bohr Effect' in the Human Body," PLoS One, vol. 6, no. 9, p. e24137, Sep. 2011.

[14] N. Koutna, "Carboxytherapy - new, non-invasive method of aesthetic medicine," Casopis lekaru ceskych, vol. 145, no. 11, pp. 841-3, 2006.

[15] D. L. Nelson and M. M. Cox, Lehninger Principles of Biochemistry 6th ed. 2013.

Patent Literature

[11] Hiroki Sakakibara, Ken Ooyachi, and Hiroaki Matsubara, "Vascularization therapy by highly

concentrated carbonated warm water bath," US20050037092 Al, 2003.