Ultrasonic manometry process in a fluid by means of microbubbles

• US 5,195,520 A
• Filed: 12/12/1991
• Issued: 03/23/1993
• Est. Priority Date: 11/05/1986
• Status: Expired due to Term

• Current Assignee: Schering Ag (Merck & Co., Inc.)
• Original Assignee: Schering Ag (Merck & Co., Inc.)
• Inventors: Poland, Hans, Schlief, Reinhard
• Primary Examiner(s): JAWORSKI, FRANCIS J
• Application Number:
  US07/806,794
• Time in Patent Office: 467 Days
• Field of Search: 128/660.02, 128/662.02, 424/9
• US Class Current: 600/438
• CPC Class Codes: A61B 8/04 Measuring blood pressure
• CPC Class Codes: A61B 8/481 involving the use of contrast agent, e.g. microbubbles introduced into the bloodstream analysis of echo signal exploiting properties of a contrast enhancer in devices for short-range imaging with acoustic waves G01S7/52039
• CPC Class Codes: A61K 49/223 Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
• CPC Class Codes: G01L 11/04 by acoustic means

Abstract

The invention relates to an ultrasonic manometry process in a fluid containing stabilized micro bubbles in an ensemble, wherein ultrasonic impulses are radiated into the fluid and brought to interact with the micro bubbles. The amplitude and/or frequency alterations in the ultrasonic scatter signals are recorded and evaluated compared with the ultrasonic impulses radiated in and/or previously recieved. Preparations for measuring blood pressure which can be used with the manometry process are described.

Claims

1. An ultrasonic manometry process in a fluid comprising introducing microbubbles into a fluid, radiating ultrasonic impulses into the fluid, and receiving and evaluating ultrasonic impulses after interaction of the radiated ultrasonic impulses with the microbubbles to determine fluid pressure, wherein the frequency range of ultrasonic impulses which are received and evaluated lie outside of the frequency range of the ultrasonic impulses radiated into the fluid and wherein the microbubbles are those created by introducing into the fluid an ensemble comprising the microbubbles and microparticles of a mixture of a semi-solid or fluid boundary surface active substance with a non-boundary surface active solid in a fluid carrier.

2. A process according to claim 1, wherein an ensemble with a known or standardized resonance spectrum is introduced into the fluid, ultrasonic impulses with a predetermined frequency range are radiated and frequencies are registered and evaluated which lie outside of the frequency range of the radiated ultrasonic impulses.

3. A process according to claim 2, wherein

ultrasonic impulses are radiated whose frequencies are in an n-th harmonic or sub-harmonic ratio to the resonance frequencies of the ensemble.

4. A process according to claim 1, wherein

signal spectra in the frequency range above the resonance frequency of the ensemble are registered and evaluated.

5. A process according to claim 1, wherein microbubbles with diameters in the range of 0.1 to 500 μ

m are used.

6. A process according to claim 1, wherein ultrasonic frequencies in the range from 800 kHz to 5 MHz are radiated in.

7. A process according to claim 1, wherein the ensemble contains as the semi-solid or fluid boundary surface active substance lecithins, polyoxyethylene fatty acid esters, glycerine polyethylene glycol ricinoleate, polyoxyethylene polyoxypropylene polymers, saccharose esters, xyloglycerides, unsaturated (C₄ -C₂₀) fatty alcohols, unsaturated (C₄ -C₂₀) fatty acids, mono-, di-, or triglycerides, or fatty acid esters as microparticles in a volume of 0.01 to 10 percent by weight.

8. A process according to claim 7, wherein the ensemble contains as the semi-solid or fluid boundary surface active substance butyl stearate, soya oil saccharose glyceride or polyethylene glycol sorbitane monostearate in a concention of 0.01 to 5 percent by weight.

9. A process according to claim 7, wherein the ensemble contains as the non-boundary surface active solid cyclodextrins, monosaccharides, disaccharides, trisaccharides, polyols or inorganic or organic salts with a concention of 5 to 50 percent by weight.

10. A process according to claim 7, wherein the ensemble contains as the non-boundary surface active solid galactose, lactose, or α

-cyclodextrin in a concentration of 5 to 50 percent by weight.

11. A process according to 7, wherein the ensemble contains as the fluid carrier which is physiologically compatible water, physiological electrolyte solution, an aqueous solution of single or multi-valent alcohols or the aqueous solution of a mono- or disaccharide.

12. A process according to claim 7, wherein the ensemble contains microparticles of a mixture of butyl stearate and galactose in water.

13. A process according to claim 7, wherein the ensemble contains microparticles of a mixture of soya oil saccharose glyceride and galactose in water.

14. A process according to claim 7, wherein the ensemble contains microparticles of a mixture of polyethylene glycol sorbitane monostearate and galactose in a physiological cooking salt solution.

15. A process according to claim 7, wherein the ensemble contains microparticles of maltose, dextrose, lactose, or galactose and gas bubbles in a fluid carrier wherein the fluid carrier consists of water, physiological electrolyte solution, or an aqueous solution of maltose, dextrose, lactose, or galactose.

16. A process according to claim 15, wherein the ensemble contains microparticles of lactose in up to 25% (percent by weight) aqueous lactose solution.

17. A process according to claim 15, wherein the ensemble contains microparticles of galactose in up to 20% aqueous galactose solution.

18. An ultrasonic manometry process in a fluid comprising introducing microbubbles into a fluid, radiating ultrasonic impulses into the fluid, and receiving and evaluating ultrasonic impulses after interaction of the radiated ultrasonic impulses with the microbubbles to determine fluid pressure, wherein the frequency range of ultrasonic impulses which are received and evaluated lie outside of the frequency range of the ultrasonic impulses radiated into the fluid and wherein the microbubbles are those created by introducing into the fluid an ensemble comprising the microbubbles and microparticles of a solid boundary surface active substance in combination with microparticles of a non-boundary surface active solid in a fluid carrier.

19. A process according to claim 18, wherein the ensemble contains as the solid boundary active substance lecithins, polyoxyethylene fatty acid esters, glycerine polyethylene glycol ricinoleate, cholesterol, polyoxyethylene polyoxypropylene polymers, saccharose esters, xyloglycerides, saturated or unsaturated (C₄ -C₂₀) fatty alcohols, saturated or unsaturated (C₄ -C₂₀) fatty acids or their metal salts, mono, di-, or triglycerides, or fatty acid esters as microparticles in a volume of 0.01 to 10 percent by weight.

20. A process according to claim 18, wherein the ensemble contains magnesium stearate, ascorbyl palmitate, saccharose monopalmitate, saccharose monostearate, or saccharose distearate as solid boundary surface active substance in the form of microparticles in a concentration of 0.01 to 5 percent by weight.

21. A process according to claim 18, wherein the ensemble contains as the microparticles of a non-boundary surface active solid cyclodextrins, monosaccharides, disaccharides, trisaccharides, polyols, or inorganic or organic salts as the microparticles with a concentration of 5 to 50 percent by weight.

22. A process according to claim 18, wherein the ensemble contains as the non-boundary surface active solid galactose, lactose, or α

-cyclodextrin as microparticles in a concentration of 5 to 50 percent by weight.

23. A process according to claim 18, wherein the ensemble contains as the fluid carrier which is physiologically compatible water, physiological electrolyte solution, an aqueous solution of single or multi-valent alcohols, or an aqueous solution of a mono- or disaccharide.

24. A process according to claim 18, wherein the ensemble contains as the physiologically compatible fluid carrier water, physiologically cooking salt solution, 10% aqueous lactose solution, or 20% aqueous galactose solution.

25. A process according to claim 18, wherein the ensemble contains microparticles of magnesium stearate and galactose, in a 20% aqueous galactose solution.

26. An ultrasonic manometry process in a fluid comprising introducing microbubbles into a fluid, radiating ultrasonic impulses into the fluid, and receiving and evaluating ultrasonic impulses after interaction of the radiated ultrasonic impulses with the microbubbles to determine fluid pressure, wherein the frequency range of ultrasonic impulses which are received and evaluated lie outside of the frequency range of the ultrasonic impulses radiated into the fluid and wherein the microbubbles are those created by introducing into the fluid an ensemble comprising a fluid mixture for absorbing and stabilizing gas bubbles filled with physiologically compatible gas, comprising the mixture of 0.01% to 10% of a tenside or tenside mixture with an aqueous carrier fluid or one miscible with water and the mixture of 0.5% to 50% of a viscosity-increasing substance or a substance mixture in an aqueous carrier fluid or carrier fluid miscible with water.

27. Preparation for measuring blood pressure by means of the ultrasonic manometry process according to claim 26 comprising

a fluid mixture for absorbing and stabilising gas bubbles filled with physiologically compatible gas, consisting of the mixture of 0.01% to 10% of a tenside or tenside mixture with an aqueous carrier fluid or carrier fluid miscible with water and the mixture of 0.5% to 50% of a viscosity-increasing substance or a substance mixture in an aqueous or water-miscible carrier fluid, wherein the two mixtures exist separately or combined.

28. A process according to claim 26, wherein the ensemble contains the mixture of 0.01 to 10% of a tenside or tenside mixture in an aqueous or water-miscible carrier fluid which contains 0.05 to 5% of a physiologically compatible carbonic acid salt and the mixture of 0.5% to 50% of a viscosity increasing substance or a substance mixture with an aqueous or water-miscible carrier fluid which contains an amount of physiologically compatible acid equivalent to the carbonic acid salt.

29. A process according to claim 26, wherein the ensemble contains a non-iongenic tenside.

30. A process according to claim 29, wherein the ensemble contains as a non-iongenic tenside polyoxyethylene polyoxypropylene polymers with the molecular weight 6800 to 8975 or 16250 to 13300.

31. A process according to claim 29, wherein the ensemble contains as a non-iongenic tenside a polyoxyethylene fatty acid ester or polyoxyethylene stearate.

32. A process according to claim 26, wherein the ensemble contains an iongenic tenside which is sodium lauryl sulfate or sodium dioctylsulfosuccinate.

33. A process according to claim 26, wherein the ensemble contains as the carrier fluid water or water-miscible, single or multi-valent alcohols, physiological electrolyte solution, or an infusion solution or mixtures thereof.