# US 2014/0193343 A1 · Measurement of body fluid volumes

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- Number: US 2014/0193343 A1
- Document ID: US20140193343A1
- Status: Published application
- Kind: A1
- Application number: 14/208,828
- Filed: 2014-03-13
- Published: 2014-07-10
- Earliest claimed: 2009-04-30
- Assignees: Pharmacophotonics, Inc. D/B/A Fast Diagnostics
- Applicants: Pharmacophotonics, Inc. D/B/A Fast Diagnostics
- Inventors: Bruce A. Molitoris; Exing Wang; Roben M. Sandoval, JR.
- Web page: https://patentgrep.com/patent/US20140193343A1

## CPC

- A61K 49/0054: {Macromolecular compounds, i.e. oligomers, polymers, dendrimers}
- A61B 5/1451: {for interstitial fluid}
- A61B 5/1455: using optical sensors, e.g. spectral photometrical oximeters
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/007: {Pulmonary tract; Aromatherapy}
- A61K 49/0002: {General or multifunctional contrast agents, e.g. chelated agents}
- A61K 49/0041: {Xanthene dyes, used in vivo, e.g. administered to a mice, e.g. rhodamines, rose Bengal (in vivo G01N)}
- A61K 49/0043: {Fluorescein, used in vivo}
- A61K 49/0052: {Small organic molecules (oligomers, polymers, dendrimers A61K49/0054)}
- G01N 33/582: {with fluorescent label}
- G01N 33/6893: {related to diseases not provided for elsewhere}
- G01N 2800/347: Renal failures; Glomerular diseases; Tubulointerstitial diseases, e.g. nephritic syndrome, glomerulonephritis; Renovascular diseases, e.g. renal artery occlusion, nephropathy
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present invention is related generally to measurement of body fluid volumes in an animal subject. The body fluid volumes of interest include extracellular fluid volume (ECFV), total vascular plasma volume (TVPV) and interstitial fluid volume (IFV). The methods are especially beneficial for subjects suffering from renal failure and particularly those undergoing renal dialysis. ECFV can be measured by administering a first molecule which is non-metabolized and permeable to vessel walls of the vascular system wherein the first molecule is distributed within the total vascular space as well as the interstitial space. TVPV can be measured by administering a second molecule which is non-metabolized and impermeable to vessel walls of the vascular system wherein the second molecule is distributed within only the vascular space. IFV can then be calculated using the equation IFV=ECFV−TVPV.

## Claims

### Claim 1

A method for measuring extracellular fluid volume (ECVF) in an animal with renal failure comprising: (a) administering a sufficient amount (A1) of a first molecule to the vascular system of the animal wherein the first molecule is non-metabolized and permeable to vessel walls of the vascular system; (b) allowing the first molecule to reach a first equilibrium steady state concentration (C1) in the vascular system of the animal; (c) measuring the C1 in the vascular system of the animal; and (d) calculating the ECFV using the equation: ECFV=A1/C1.

### Claim 2 (depends on 1)

The method of claim 1 wherein the administration of the first molecule is by intravenous injection of a first injectate containing the first molecule.

### Claim 3 (depends on 2)

The method of claim 2 wherein the injection is a bolus injection or an infusion.

### Claim 4 (depends on 1)

The method of claim 1 wherein the administration is by inhalation.

### Claim 5 (depends on 1)

The method of claim 1 wherein the first molecule has a molecular size of from about 1 kDa to about 20 kDa.

### Claim 6 (depends on 1)

The method of claim 1 wherein the first molecule is a dextran.

### Claim 7 (depends on 1)

The method of claim 1 wherein the first molecule is labeled with a first fluorescent dye having a first excitation wavelength and a first emission wavelength.

### Claim 8 (depends on 7)

The method of claim 7 wherein the first fluorescent dye is selected from the group consisting of xanthene dye, CAL FLOUR®, ALEXA FLUOR®, OREGON GREEN®, carbocyanine, fluorescein, fluorescein isothiocyanate (FITC), carboxy fluoresecein, cyanine, rhodamine, tetramethylrhodamine (Tamra), tetramethyl rhodamine isothiocyanate (TRITC), X rhodamine isothiocyanate (XRITC), TEXAS RED® and indocyanine green (ICG).

### Claim 9 (depends on 1)

The method of claim 1 wherein the animal is a mammal.

### Claim 10 (depends on 1)

The method of claim 1 wherein the mammal is a human.

### Claim 11 (depends on 1)

The method of claim 1 wherein the renal failure is acute or chronic.

### Claim 12 (depends on 1)

The method of claim 1 wherein the renal failure is temporary or permanent.

### Claim 13 (depends on 1)

The method of claim 1 wherein the step (c) of measuring C1 includes: (a) withdrawing a sample of blood from the vascular system of the animal; (b) obtaining a plasma supernatant from the blood sample; and (c) measuring C1 in the supernatant of the sample.

### Claim 14 (depends on 13)

The method of claim 13 wherein C1 is detected and quantified in vitro by the fluorescence intensity of the molecule.

### Claim 15 (depends on 13)

The method of claim 13 wherein C1 is detected and quantified in vitro using an ELISA assay containing antibodies to the fluorescent dye.

### Claim 16 (depends on 1)

The method of claim 1 wherein the step (c) is performed in vivo.

### Claim 17

A method for measuring total vascular plasma volume (TVPV) of an animal comprising: (a) administering a sufficient amount (A2) of a second molecule to the vascular system of the animal, wherein the second molecule is non-metabolized and impermeable to vessel walls of the vascular system; (b) allowing the second molecule to reach a second equilibrium steady state concentration in the plasma within the vascular system of the animal; (c) measuring the second equilibrium steady state concentration (C2) of the second molecule; and (d) calculating the TVPV using the equation: TVPV=A2/C2.

### Claim 18 (depends on 17)

The method of claim 17 wherein the administration of the second molecule is by intravenous injection of a second injectate containing the second molecule.

### Claim 19 (depends on 18)

The method of claim 18 wherein the injection is a bolus injection or an infusion.

### Claim 20 (depends on 18)

The method of claim 18 wherein the administration is by inhalation.

### Claim 21 (depends on 17)

The method of claim 17 wherein the first molecule has a molecular size of from about 70 kDa to about 500 kDa.

### Claim 22 (depends on 17)

The method of claim 17 wherein the first molecule is a dextran.

### Claim 23 (depends on 17)

The method of claim 17 wherein the second molecule is labeled with a second fluorescent dye having a second excitation wavelength and a second emission wavelength.

### Claim 24 (depends on 17)

The method of claim 17 wherein the second fluorescent dye is selected from the group consisting of xanthene dye, CAL FLOUR®, ALEXA FLUOR®, OREGON GREEN®, carbocyanine, fluorescein, fluorescein isothiocyanate (FITC), carboxy fluoresecein, cyanine, rhodamine, tetramethylrhodamine (Tamra), tetramethyl rhodamine isothiocyanate (TRITC), X rhodamine isothiocyanate (XRITC), TEXAS RED® and indocyanine green (ICG).

### Claim 25 (depends on 17)

The method of claim 17 wherein the step (c) of measuring C2 includes: (a) withdrawing a sample of blood from the vascular system of the animal; (b) obtaining a plasma supernatant from the blood sample; and (c) measuring C2 in the supernatant of the sample.

### Claim 26 (depends on 25)

The method of claim 25 wherein C2 is detected and quantified in vitro by the fluorescence intensity of the molecule.

### Claim 27 (depends on 25)

The method of claim 25 wherein C2 is detected and quantified in vitro using an ELISA assay containing antibodies to the fluorescent dye.

### Claim 28 (depends on 25)

The method of claim 25 wherein the step (c) is performed in vivo.

### Claim 29

A method for determining the interstitial fluid volume (IFV) in an animal comprising: (a) determining the extracellular fluid volume (ECFV) of the animal; (b) determining the total vascular plasma volume (TVPV) of the animal; and (c) calculating the IFV of the animal using the equation: IFV=ECFV−TVPV.