WO2003084604A1 - Method for measuring blood urea level by reverse iontophoresis - Google Patents
Method for measuring blood urea level by reverse iontophoresis Download PDFInfo
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- WO2003084604A1 WO2003084604A1 PCT/TR2003/000032 TR0300032W WO03084604A1 WO 2003084604 A1 WO2003084604 A1 WO 2003084604A1 TR 0300032 W TR0300032 W TR 0300032W WO 03084604 A1 WO03084604 A1 WO 03084604A1
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- Prior art keywords
- solution
- urea
- determining
- urea level
- blood
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- 239000004202 carbamide Substances 0.000 title claims abstract description 48
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 title claims abstract description 47
- 239000008280 blood Substances 0.000 title claims abstract description 35
- 210000004369 blood Anatomy 0.000 title claims abstract description 35
- 238000000034 method Methods 0.000 title claims abstract description 28
- 108010046334 Urease Proteins 0.000 claims description 7
- 230000008859 change Effects 0.000 claims description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 5
- 108090000790 Enzymes Proteins 0.000 claims description 2
- 102000004190 Enzymes Human genes 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 238000002798 spectrophotometry method Methods 0.000 claims description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 10
- 239000008103 glucose Substances 0.000 description 10
- 239000012528 membrane Substances 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 6
- 150000002500 ions Chemical class 0.000 description 5
- 238000012546 transfer Methods 0.000 description 5
- 238000009792 diffusion process Methods 0.000 description 4
- 238000005259 measurement Methods 0.000 description 3
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- 208000037157 Azotemia Diseases 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 238000005370 electroosmosis Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000009852 uremia Diseases 0.000 description 2
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 208000031220 Hemophilia Diseases 0.000 description 1
- 208000009292 Hemophilia A Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 208000015294 blood coagulation disease Diseases 0.000 description 1
- 230000009852 coagulant defect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 210000000245 forearm Anatomy 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 238000011169 microbiological contamination Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000001139 pH measurement Methods 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14539—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring pH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/20—Applying electric currents by contact electrodes continuous direct currents
- A61N1/30—Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
Definitions
- This invention relates to a method for measuring urea level in human blood by reverse iontophoresis and a device -urea meter- using the method.
- Measurement and determination of urea level is particularly important for patients with insufficient kidney function, neonates, pregnant women, or for the epidemiological screening.
- Patients with uremia are influenced both emotionally and physically due to giving blood samples frequently for undergoing subsequent dialysis.
- Proposed invention relates to reverse iontophoresis.
- Such a method has been in use for example in WO 03000340 disclosing a method for non-invasively determining the relative levels of two substances present in a biological system includes the steps of extracting by reverse iontophoresis charged and uncharged substances from said biological system.
- WO 03000340 solely discloses the use of reverse iontophoresis for a biological system and does not teach or suggest any method for measuring and determining the urea level in human blood.
- WO 03010538 discloses a method and a device for increasing reverse iontophoresis flux so that non-invasive extraction of uncharged and charged permanent molecules alike through the skin.
- WO 03010538 does not suggest a solution for measuring and determining urea level in human blood.
- Iontophoresis usage is known from various applications as in attached reference list, to pass some compounds through the human skin or to enhance the permeability.
- Reverse iontophoresis is utilized for taking glucose from the blood to measure the blood glucose level.
- the object of the present invention is to measure and determine urea level in human blood securely and without involving any contamination risk.
- Another object of the present invention is to measure and determine urea level in human blood painlessly.
- Yet further object of the present invention is to monitor of urea level in human blood.
- the urea level can be obtained in a very short period of time without taking blood or any other biological samples from the patient.
- ions molecules or atoms having a net charge or partially charged
- Electrodes or similar tools are provided to the both side of the membrane and the applied electrical current or potential (direct or alternative current, square, sinus or triangular or even different frequencies and/or currencies) can be applied as needed.
- the ions in the solution migrate according to their charges and their movement is in proportional to the current. For instance, positively charged ions migrate to the negative electrode side and vice versa. While the charged ions are migrating according to the electrical current, they also drag the uncharged molecules along with themselves. At this instance, traveling from one side to the other side of the membrane creates a flow, a turbulence occurs (this is so called an electro-osmotic flow). Therefore the unchanged particles (atoms/molecules) can also be able to pass through the membrane by being pulled into this vortex or into the motion and, this passage occurs at a much faster rate than that of passive diffusion.
- the amount of urea drawn into the solution (5) is measured-calculated according to the change of pH induced by the urease.
- Urease is an enzyme specific to urea. When it comes across with urea, NH 3 is produced, and it raises the pH value of the solution. This is directly related with the amount of urea.
- One ml of 1 % urease in the isotonic saline solution is added into the 5 ml of solution obtained form the reverse iontophoresis procedure (which contains urea drawn through the patient's skin). After 10 minutes, the mixture-new solution's pH is measured. The relationship between the patient's blood urea level and the pH values obtained in our experiment is shown in Figure-5.
- the composition of the electrodes is Ag for the anode and AgCI for the cathode. These electrodes do not cause any pH level change, but other electrodes can also be used such as cupper, wanadium, steel, gold etc.
- determination of urea level in solution is performed by measuring thereof through using spectrophotometric methods or by determining the change in the electrical properties of the skin in replace of the above-mentioned determination of change in pH.
- the method in the scope of the present invention is performed by practicing on a device i.e. an arm watch-like device or might be called as a urea-meter.
- the urea watch comprises a (+) electrode (6); and a solution (5) containing NaCI and urease in the inside of the watch casing-container (3) being in touch with the skin surface (7).
- the watch further comprises a dialysis membrane which protects from any leakage of the solution and provides the transfer of urea through (this membrane can be a hemodialysis membrane).
- a gel comprising a collection medium instead of solution mentioned above can be utilized.
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- Life Sciences & Earth Sciences (AREA)
- Physics & Mathematics (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Pathology (AREA)
- Molecular Biology (AREA)
- Surgery (AREA)
- Medical Informatics (AREA)
- Heart & Thoracic Surgery (AREA)
- Biophysics (AREA)
- Optics & Photonics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Radiology & Medical Imaging (AREA)
- Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
A method for measuring and determining urea level in human blood by reverse iontophoresis comprising the following steps of; -placing an anode electrode on skin,- placing a container comprising a solution and a cathode electrode on skin- applying electric current to the anode electrode and the cathode electrode so that an electrical circuit is established there between. whereby urea molecules migrate from blood into the container.
Description
METHOD FOR MEASURING BLOOD UREA LEVEL BY REVERSE
IONTOPHORESIS
TECHNICAL FIELD
This invention relates to a method for measuring urea level in human blood by reverse iontophoresis and a device -urea meter- using the method.
Measurement and determination of urea level is particularly important for patients with insufficient kidney function, neonates, pregnant women, or for the epidemiological screening.
BACKGROUND ART
Various attempts have been observed for measuring and determining urea level in human blood, including biological-based methods and sampling of human blood.
These conventionally utilized methods offer some reasonable outcomes in the sense of determining urea level in human blood. However, as it is acknowledged by a person skilled in the art, these practices accompany with some disadvantages comprising microbiological contamination, embolism as well as causing pain to the patient, since these exercised methods are associated with taking biologic or blood samples and subsequently analyzing these samples so as to determine the urea level in the blood.
The risks involved are not limited with the present practices as set forth above, since taking blood samples is particularly important for patients with diabetes, hemophilia or some coagulation disorders and more particularly the hemophiliacs.
Further disadvantages with the present practices apply for neonates and infants with regard to the risk of infection and the difficulty for performing such taking blood samples from the neonates and infants.
As for epidemiological screening for uremia, there exists possibility of mixing up the samples/injectors and thus lead to a greater infectious contamination.
Yet another disadvantage with the existing practices is obvious for pregnant women, since taking blood thereof also poses additional discomfort and difficulty.
Patients with uremia are influenced both emotionally and physically due to giving blood samples frequently for undergoing subsequent dialysis.
Proposed invention relates to reverse iontophoresis. Such a method has been in use for example in WO 03000340 disclosing a method for non-invasively determining the relative levels of two substances present in a biological system includes the steps of extracting by reverse iontophoresis charged and uncharged substances from said biological system.
WO 03000340 solely discloses the use of reverse iontophoresis for a biological system and does not teach or suggest any method for measuring and determining the urea level in human blood.
WO 03010538 discloses a method and a device for increasing reverse iontophoresis flux so that non-invasive extraction of uncharged and charged permanent molecules alike through the skin.
Therefore WO 03010538 does not suggest a solution for measuring and determining urea level in human blood.
Iontophoresis usage is known from various applications as in attached reference list, to pass some compounds through the human skin or to enhance the permeability. Reverse iontophoresis, however, is utilized for taking glucose from the blood to measure the blood glucose level.
DISCLOSURE OF THE INVENTION
The object of the present invention is to measure and determine urea level in human blood securely and without involving any contamination risk.
Another object of the present invention is to measure and determine urea level in human blood painlessly.
Yet further object of the present invention is to monitor of urea level in human blood.
With this proposed invention, the urea level can be obtained in a very short period of time without taking blood or any other biological samples from the patient.
In iontophoresis procedure, by using an electrical current (producing an electrical gradient), the ions (molecules or atoms having a net charge or partially charged) can be carried to the other side of the membrane according to applied current and electrical charge and it is possible to control by iontophoresis. Electrodes or similar tools are provided to the both side of the membrane and the applied electrical current or potential (direct or alternative current, square, sinus or triangular or even different frequencies and/or currencies) can be applied as needed.
The ions in the solution migrate according to their charges and their movement is in proportional to the current. For instance, positively charged ions migrate to the negative electrode side and vice versa. While the charged ions are
migrating according to the electrical current, they also drag the uncharged molecules along with themselves. At this instance, traveling from one side to the other side of the membrane creates a flow, a turbulence occurs (this is so called an electro-osmotic flow). Therefore the unchanged particles (atoms/molecules) can also be able to pass through the membrane by being pulled into this vortex or into the motion and, this passage occurs at a much faster rate than that of passive diffusion.
When the molecular structure of urea investigated as in Figure-1 , although it is known to behave as not charged molecules, it is seen that some local charges are present on the molecule. According to the experiments conducted, the higher urea transportation was observed than passive diffusion when urea was present at the positive electrode side because of the positive local charges on the molecule as in Figure-2. There is also a possibility that the electro-osmotic flow was partially influential for this transfer. However, during the transfer, if the other small but charged ions like potassium and sodium are present in the solution, the transfer rate decreases; but still the transfer is much larger and faster than the passive diffusion.
These experiments were repeated using human skin (7) as the membrane, and similar results were obtained. So, since the urea molecules are partially charged with + load the 'reverse- iontophoresis' can be applied. For this, an anode, (+) electrode (6), can be placed right on the skin (7) surface in the forearm, and near this place, a cathode (4), (-) electrode, is inserted into a container (3) which contains an isotonic saline solution (5). When the electrical current is applied by a power supplier (1 ), the urea molecules will migrate from blood to the container (3) on the outside (Figure-3). This will be in direct proportion to the current and area used.
In experiments conducted, 10 ml isotonic saline solution has been placed into the container (3). The area of the container is 12.5 cm2. The current is supplied with a 1000 uA, measured by an ampere-meter (2), level and applied for 5
minutes. After the current is terminated the values in the solution are measured. These experiments have been conducted on volunteers as it is explained above with the reverse iontophoresis procedure and the solution (5) in the container (3) in which urea is accumulated is taken and the amount of urea in this solution is determined.
The levels of urea in this solution were analyzed in biochemistry laboratory using urease method. In the process of this analysis, after adding a reactive agent, the ultraviolet absorbency at 305 nm is measured. The measured absorbency values placed into the calibration equation and the urea levels have been measured in 'mg/dl' terms. When the blood urea levels and the results obtained by reverse iontophoresis procedure are compared, (when all else like current, surface and time period held constant), it has been observed that there has been a definite relationship in between the two methods (Figure-4).
In this proposed system, the amount of urea drawn into the solution (5) is measured-calculated according to the change of pH induced by the urease. Urease is an enzyme specific to urea. When it comes across with urea, NH3 is produced, and it raises the pH value of the solution. This is directly related with the amount of urea. One ml of 1 % urease in the isotonic saline solution is added into the 5 ml of solution obtained form the reverse iontophoresis procedure (which contains urea drawn through the patient's skin). After 10 minutes, the mixture-new solution's pH is measured. The relationship between the patient's blood urea level and the pH values obtained in our experiment is shown in Figure-5. In the experiments, the composition of the electrodes is Ag for the anode and AgCI for the cathode. These electrodes do not cause any pH level change, but other electrodes can also be used such as cupper, wanadium, steel, gold etc.
Alternatively, determination of urea level in solution is performed by measuring thereof through using spectrophotometric methods or by determining the
change in the electrical properties of the skin in replace of the above-mentioned determination of change in pH.
The method in the scope of the present invention is performed by practicing on a device i.e. an arm watch-like device or might be called as a urea-meter. The urea watch comprises a (+) electrode (6); and a solution (5) containing NaCI and urease in the inside of the watch casing-container (3) being in touch with the skin surface (7). The watch further comprises a dialysis membrane which protects from any leakage of the solution and provides the transfer of urea through (this membrane can be a hemodialysis membrane). There is also a (-) electrode (4) at the other side of the skin (7) which can be mounted at the strap of the watch, the pH measurement and the batteries must be present to provide a current.
In an alternative embodiment, the possibility of using a gel comprising a collection medium instead of solution mentioned above can be utilized. There is also a microcomputer/microprocessor and the software for the measurement of the urea level in blood and the pre-calibrated pH values and can be indicated the urea level in blood.
References
1-Tiemey M.J, Tamada J.A., Potts R.O.,. Jovanovic L, Garg S., Clinical evaluation of the GlucoWatch® biographer: a continual, non-invasive glucose monitor for patients with diabetes, Biosensors & Bioelectronics 16 (2001 ) 621— 629.
2-Brunner, G.A., Ellmerer, M., Sendlhofer, G., et al., 1998. Validation of home blood glucose meters with respect to clinical and analytical approaches. Diab. Care 21 (4), 585-590.
3-Cambiaso, A., Delfino, L., Grattarola, M., Verreschi, G., Ashworth, D., Maines, A., et al., 1996. Modelling and simulation of a diffusion limited glucose biosensor. Sens. Act. B. 33, 203-207.
4-Tiemey, M.J., Tamada, J.A., Potts, R.O., et al., 2000. The Gluco-Watch biographer: a frequent, automatic, and noninvasive glucose monitor. Ann. Med. 32, 632-641.
5-Zhang, Y., Hu, Y., Wilson, G.W., Moatti-Sirat, D., Poitout, V., Reach, G., 1994. Elimination of the acetaminophen interference in an implantable glucose sensor. Anal. Chem. 66, 1183-1188.
6-Clarke, W.L., Cox, D., Gonder-Frederick, L.A., Carter, W., Pohl, S.L., 1987. Evaluating clinical accuracy of systems for self-monitoring of blood glucose. Diab. Care 10 (5), 622-628.
Deming, W.E., 1943. Statistical Adjustment of Data. Wiley, New York.
7-Garg, S.K., Potts, R.O., Ackerman, N.R., Fermi, S.J., Tamada, J.A., Chase, H.P., 1999. Correlation of fingerstick blood glucose measurements with GlucoWatch biographer glucose results in young subjects with type 1 diabetes. Diab. Care 22, 1708-1714.
8-Ginsberg, B.H., 1992. An overview of minimally invasive technologies. Clin. Chem. 38, 1596-1600.
9-Kilpatrick, E.S., McLeod, M.J., Rumley, A.G., Small, M., 1994. A ward comparison between the One Touch II and Glucometer II blood glucose meters. Diab. Med. 11 , 214-217.
10-Kurnik, R.T., Oliver, J.J., Waterhouse, S.R., Dunn, T., Jayalakshmi, Y., Lesho, M., et al., 1999. Application of the mixtures of experts algorithm for signal processing in a noninvasive glucose monitoring system. Sens. Act. B. 60, 1-8.
Claims
1. A method for measuring and determining urea level in human blood by reverse iontophoresis comprising the following steps of;
- placing an anode electrode on skin,
- placing a container comprising a solution and a cathode electrode on skin
- applying electric current to the anode electrode and the cathode electrode so that an electrical circuit is established therebetween. whereby urea molecules migrate from blood into the container.
2. The method according to claim 1 , said solution is an isotonic saline solution.
3. The method according to claim 1 , further comprising the following step of;
- measuring the urea level in the solution.
4. The method according to claim 1 , further comprising the following step of;
- determining the urea level in the solution using urease method being an enzyme specific to urea and comprising incorporating a reactive agent and measuring ultraviolet absorbency thereof,
5. The method according to claim 4, further comprising the following step of;
- calculating the urea level according to change of pH induced by the urease.
6. The method according to claim 4, further comprising the following step of; - using spectrophotometric methods for determining the urea level.
7. The method according to claim 4, further comprising the following step of;
- determining the change in the electrical properties of the skin for determining the urea level.
8. A device for measuring and determining urea level in human blood by reverse iontophoresis comprising;
- an anode electrode (6) placed on skin (7), - a container (3) comprising a solution and a cathode electrode (4) placed on skin (7),
- an power supplier (1), said power supplier (1) is connected to the anode electrode (6) and the cathode electrode (4) for establishing an electric circuit between the anode electrode (6) and the cathode electrode (4)
whereby urea molecules migrate from blood into the container (3).
9. The device according to claim 8, characterized in that the anode electrode (6), the container (3) comprising the solution (5) and a cathode electrode (4), the power supplier (1 ) are embodied into an arm watch-like device.
10. The device according to claim 8 to 9, characterized in that the power supplier (1 ) is a direct electric current supplier.
11. The device according to claim 8 to 10, characterized in that said solution is an isotonic saline solution.
12. The device according to claim 8 to 11 , characterized in that the anode electrode (6) is an Ag.
13. The device according to claim 8 to 12, characterized in that the cathode electrode (4) is an AgCI.
14. The device according to claim 8 to 13, characterized in that a gel comprising a collection medium is used instead of the solution.
15. The device according to claim 8 to 14, characterized in that a software controlled micro-computer is provided for determining the urea level in blood.
16. The device according to claim 4 to 9, characterized in that a gel comprising a collection medium is used instead of the solution.
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2003581841A JP4495975B2 (en) | 2002-04-08 | 2003-04-08 | A method for measuring blood urea concentration by reverse iontophoresis. |
| US10/510,779 US7231242B2 (en) | 2002-04-08 | 2003-04-08 | Method for measuring blood urea level by reverse iontophoresis |
| AT03721271T ATE480296T1 (en) | 2002-04-08 | 2003-04-08 | DEVICE FOR MEASURING THE URE NITROGEN LEVEL IN THE BLOOD USING INVERSE IONTOPHORESIS |
| DE60334106T DE60334106D1 (en) | 2002-04-08 | 2003-04-08 | DEVICE FOR MEASURING HARD NITROGEN STATE IN BLOOD WITH INVERSE IONTOPHORESIS |
| EP03721271A EP1526891B1 (en) | 2002-04-08 | 2003-04-08 | Device for measuring blood urea level by reverse iontophoresis |
| AU2003224595A AU2003224595A1 (en) | 2002-04-08 | 2003-04-08 | Method for measuring blood urea level by reverse iontophoresis |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2002/00942 | 2002-04-08 | ||
| TR2002/00942A TR200200942A2 (en) | 2002-04-08 | 2002-04-08 | Urea meter / urea clock: detection of urea in human blood by reverse iontophoresis, without taking blood or biological samples. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2003084604A1 true WO2003084604A1 (en) | 2003-10-16 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/TR2003/000032 WO2003084604A1 (en) | 2002-04-08 | 2003-04-08 | Method for measuring blood urea level by reverse iontophoresis |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US7231242B2 (en) |
| EP (1) | EP1526891B1 (en) |
| JP (1) | JP4495975B2 (en) |
| CN (1) | CN100431641C (en) |
| AT (1) | ATE480296T1 (en) |
| AU (1) | AU2003224595A1 (en) |
| DE (1) | DE60334106D1 (en) |
| RU (1) | RU2373969C2 (en) |
| TR (1) | TR200200942A2 (en) |
| WO (1) | WO2003084604A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6824246B2 (en) * | 2002-11-23 | 2004-11-30 | Kia Silverbrook | Thermal ink jet with thin nozzle plate |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2724115A1 (en) * | 1994-09-02 | 1996-03-08 | Elf Aquitaine | IONOPHORESIS DEVICE FOR TRANSCUTANEOUS DELIVERY OF AN ACTIVE INGREDIENT TO A SUBJECT ENSURING ACCURATE CONTROL OF DOSAGE |
| US5591123A (en) * | 1983-08-18 | 1997-01-07 | Drug Delivery Systems Inc. | Programmable control mounting system for transdermal drug applicator |
| US5771890A (en) * | 1994-06-24 | 1998-06-30 | Cygnus, Inc. | Device and method for sampling of substances using alternating polarity |
| EP1082940A1 (en) * | 1998-06-05 | 2001-03-14 | Hisamitsu Pharmaceutical Co., Inc. | Iontophoresis device structural body and method for detecting in-vivo component |
| WO2003000340A1 (en) | 2001-06-22 | 2003-01-03 | Universite De Geneve | Method for non-invasively determining the relative levels of two biological substances |
| WO2003010538A1 (en) | 2001-07-23 | 2003-02-06 | Aciont Inc. | Method and apparatus for increasing, flux during reverse iontophoresis |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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- 2003-04-08 EP EP03721271A patent/EP1526891B1/en not_active Expired - Lifetime
- 2003-04-08 CN CNB038128624A patent/CN100431641C/en not_active Expired - Fee Related
- 2003-04-08 AT AT03721271T patent/ATE480296T1/en not_active IP Right Cessation
- 2003-04-08 AU AU2003224595A patent/AU2003224595A1/en not_active Abandoned
- 2003-04-08 WO PCT/TR2003/000032 patent/WO2003084604A1/en active Application Filing
- 2003-04-08 US US10/510,779 patent/US7231242B2/en not_active Expired - Fee Related
- 2003-04-08 JP JP2003581841A patent/JP4495975B2/en not_active Expired - Fee Related
- 2003-04-08 RU RU2004133037/14A patent/RU2373969C2/en not_active IP Right Cessation
- 2003-04-08 DE DE60334106T patent/DE60334106D1/en not_active Expired - Lifetime
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| US5591123A (en) * | 1983-08-18 | 1997-01-07 | Drug Delivery Systems Inc. | Programmable control mounting system for transdermal drug applicator |
| US5771890A (en) * | 1994-06-24 | 1998-06-30 | Cygnus, Inc. | Device and method for sampling of substances using alternating polarity |
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| EP1082940A1 (en) * | 1998-06-05 | 2001-03-14 | Hisamitsu Pharmaceutical Co., Inc. | Iontophoresis device structural body and method for detecting in-vivo component |
| WO2003000340A1 (en) | 2001-06-22 | 2003-01-03 | Universite De Geneve | Method for non-invasively determining the relative levels of two biological substances |
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Also Published As
| Publication number | Publication date |
|---|---|
| CN100431641C (en) | 2008-11-12 |
| DE60334106D1 (en) | 2010-10-21 |
| US7231242B2 (en) | 2007-06-12 |
| US20050273045A1 (en) | 2005-12-08 |
| ATE480296T1 (en) | 2010-09-15 |
| EP1526891A1 (en) | 2005-05-04 |
| JP2005522246A (en) | 2005-07-28 |
| AU2003224595A1 (en) | 2003-10-20 |
| TR200200942A2 (en) | 2004-02-23 |
| CN1658925A (en) | 2005-08-24 |
| EP1526891B1 (en) | 2010-09-08 |
| JP4495975B2 (en) | 2010-07-07 |
| RU2373969C2 (en) | 2009-11-27 |
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