# US 11,305,045 B2 · Blood processing apparatus and method for detoxifying bacterial lipopolysaccharide

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- Number: US 11,305,045 B2
- Document ID: US11305045B2
- Status: Granted
- Kind: B2
- Application number: 17/395,267
- Filed: 2021-08-05
- Published: 2021-11-25
- Granted: 2022-04-19
- Earliest claimed: 2020-04-29
- Assignees: Orth Consulting, LLC
- Applicants: Orth Consulting, LLC
- Inventors: Donald S. Orth
- Web page: https://patentgrep.com/patent/US11305045B2

## CPC

- A61M 1/3679: {by absorption (A61M1/3675 takes precedence)}
- A61M 1/3687: {Chemical treatment (A61M1/3675 takes precedence)}
- A61K 8/66: Enzymes
- A61M 1/3618: {Magnetic separation}
- A61M 1/3623: {Means for actively controlling temperature of blood}
- A61M 1/3653: {Interfaces between patient blood circulation and extra-corporal blood circuit}
- B01J 20/22: comprising organic material
- C12N 11/14: Enzymes or microbial cells immobilised on or in an inorganic carrier
- C12N 11/18: Multi-enzyme systems
- C12Q 1/42: involving phosphatase
- C12Y 301/03001: Alkaline phosphatase (3.1.3.1)
- C12Y 306/01005: Apyrase (3.6.1.5), i.e. ATP diphosphohydrolase
- A61M 2202/20: Pathogenic agents
- A61M 2202/203: Bacteria
- A61M 2202/206: Viruses
- A61M 2205/103: rotating
- A61M 2205/12: with interchangeable cassettes forming partially or totally the fluid circuit
- A61M 2205/3303: Using a biosensor
- A61M 2205/3368: Temperature
- A61M 2205/36: related to heating or cooling
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}
- 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)
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Y: ENZYMES

## Abstract

A detoxification method includes the steps of inducing flow of patient blood through an extracorporeal device inlet and outlet in fluid connection to the circulatory system of a patient. Biological agents including lipopolysaccharide (LPS) contained within patient blood can be detoxified by passing patient blood over a biochemical reactor surface having attached or immobilized Saccharomyces boulardii alkaline phosphatase enzyme, with the biochemical reactor being contained within the extracorporeal device. An acyloxyacyl hydrolase enzyme may also be used on the biochemical reactor surface.

## Claims

### Claim 1

A detoxification method, comprising:
inducing flow of blood of a patient through an extracorporeal device inlet and outlet; and
detoxifying at least one biological agent contained within the blood by passing the blood over at least one biochemical reactor surface having attached phosphatase enzyme and acyloxyacyl hydrolase enzyme, with the at least one biochemical reactor surface being contained within the extracorporeal device and wherein the at least one biological agent is selected from the group consisting of:
Gram negative bacterial lipopolysaccharide (LPS);
Gram negative bacterial flagellin;
Gram positive bacterial extracellular lipoteichoic acid;
Gram positive bacterial flagellin;
one or more bacterial extracellular nucleotides selected from adenosine triphosphate (ATP), adenosine diphosphate (ADP), deoxyribonucleic acid (DNA), and ribonucleic acid (RNA),
one or more yeast extracellular nucleotides selected from ATP, ADP, DNA and RNA,
one or more fungal extracellular nucleotides selected from ATP, ADP, DNA and RNA,
one or more viral extracellular nucleotides selected from DNA and RNA, and
one or more host extracellular nucleotides selected from ATP, ADP, DNA, and RNA, and combinations thereof.

### Claim 2 (depends on 1)

The detoxification method of claim 1, further comprising connecting the extracorporeal device inlet and outlet to the patient.

### Claim 3 (depends on 1)

The detoxification method of claim 1, wherein inducing the flow of the blood of the patient through the extracorporeal device inlet and outlet is performed continuously.

### Claim 4 (depends on 1)

The detoxification method of claim 1, wherein the inducing the flow of blood of the patient through the extracorporeal device inlet and outlet comprises removing batches of blood from the patient and, for each batch of the batches of blood, passing the batch through the extracorporeal device inlet and outlet and returning the batch to the patient.

### Claim 5 (depends on 1)

The detoxification method of claim 1, wherein the phosphatase enzyme detoxifies the at least one biological agents contained within the blood by dephosphorylation.

### Claim 6 (depends on 1)

The detoxification method of claim 1, wherein the acyloxyacyl hydrolase enzyme detoxifies the at least one biological agent contained within the blood by deacylation.

### Claim 7 (depends on 1)

The detoxification method of claim 1, wherein detoxifying the at least one biological agent contained within the blood of the patient therapeutically treats at least one of sepsis, septic shock, inflammation, bacteremia, a yeast infection, a fungal infection, a viral infections, systemic inflammatory response syndrome (SIRS), Gram negative bacterial lipopolysaccharide (LPS) in the blood, IBD, IBS, Crohn's disease, ulcerative colitis, enterocolitis, NEC, meningitis, meningococcemia, trauma, hemorrhagic shock, a burns, liver disease, pancreatitis, periodontal disease, pneumonia, cystic fibrosis, asthma, A1AT deficiency, COPD, pulmonary fibrosis, tuberculosis, coronary heart disease, congestive heart failure, renal disease, hemolytic uremic syndrome, kidney disease, an autoimmune diseases, rheumatoid arthritis, systemic lupus erythematosus, a mast cell activation disorders, cancer, Alzheimer's disease, diabetes, infection resulting in LPS or lipoteichoic acid in the blood, an abscess resulting in LPS or lipoteichoic acid in the blood, a protein aggregation disorder, a neurodegenerative disease, Parkinson's disease, amyloidosis, and a condition following surgery.

### Claim 8 (depends on 1)

The detoxification method of claim 1, wherein the phosphatase enzyme and the acyloxyacyl hydrolase enzyme are covalently attached to the at least one biochemical reactor surface.

### Claim 9 (depends on 1)

The detoxification method of claim 1, wherein the at least one biochemical reactor surface comprises at least one of one or more surfaces of capillary tubing and surfaces of microbeads.

### Claim 10 (depends on 1)

The detoxification method of claim 1, wherein the at least one biochemical reactor surface comprises surfaces of magnetic microbeads.

### Claim 11 (depends on 1)

The detoxification method of claim 1, wherein the at least one biochemical reactor surface is provided with continuous flow of the blood that continues until the at least one biological agents being detoxified has each been reduced to predetermined levels in the blood.