# US 2013/0280232 A1 · Use of alkaline phosphatase for the detoxification of lps present at mucosal barriers

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- Number: US 2013/0280232 A1
- Document ID: US20130280232A1
- Status: Published application
- Kind: A1
- Application number: 13/768,866
- Filed: 2013-02-15
- Published: 2013-10-24
- Earliest claimed: 2004-02-04
- Assignees: Pharmaaware Sepsis B.V.
- Inventors: Rudi BRANDS; Klaas POELSTRA
- Web page: https://patentgrep.com/patent/US20130280232A1

## CPC

- A61K 38/465: {acting on ester bonds (3.1), e.g. lipases, ribonucleases}
- A23C 9/1216: {Other enzymes}
- A23L 29/06: {Enzymes}
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/02: Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 13/12: of the kidneys
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/04: Antibacterial agents
- A61P 35/00: Antineoplastic agents
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 39/02: Antidotes
- A61P 41/00: Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
- C12Y 301/03001: Alkaline phosphatase (3.1.3.1)
- 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)
- A23C: DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; PREPARATION THEREOF (preservation thereof A23B11/00)
- A23L: FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF (preservation thereof A23B)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12Y: ENZYMES

## Abstract

The present invention provides a use for alkaline phosphatase for the manufacture of a medicament for the prevention or reduction of toxic LPS influx through a mucosal lining of a mammalian body cavity. A source of alkaline phosphatase is administered for the prophylaxis or treatment of LPS mediated or exacerbated diseases. The invention also provides compositions comprising a source of alkaline phosphatase for the prevention or reduction of (toxic) LPS influx or passage through mucosal layers.

## Claims

### Claim at position 1

1-27. (canceled)

### Claim 28

A method for preventing or reducing LPS toxicity in a subject, comprising administering a composition comprising an alkaline phosphatase (AP) that is suitable for preventing or reducing LPS-induced toxicity in a subject suffering from or at risk of suffering from a liver disease, wherein the AP is delivered to the gastro-intestinal tract of the subject to prevent or reduce said LPS toxicity.

### Claim 29 (depends on 28)

The method according to claim 28, wherein the subject suffers from an LPS mediated or LPS exacerbated disease or condition.

### Claim 30 (depends on 29)

The method according to claim 29, wherein the LPS mediated or LPS exacerbated disease or condition i s selected from the group consisting of inflammatory diseases of the gastro-intestinal tract, inflammatory bowel disease, sepsis/septic shock, systemic inflammatory response syndrome (SIRS), meningococcemia, trauma/hemorrhagic shock, burn injuries, cardiovascular surgery/cardiopulmonary bypass, liver surgery/transplant, (necrotizing) enterocolitis, periodontal disease, pneumonia, cystic fibrosis, asthma, coronary heart disease, congestive heart failure, renal disease, hemolytic uremic syndrome, kidney dialysis, autoimmune diseases, cancer, Alzheimer, rheumatoid arthritis, lupus, systemic lupus erythematosus, decreased perfusion of the gastro-intestinal tract and ischemia of the gastro-intestinal tract.

### Claim 31 (depends on 28)

The method according to claim 28, wherein the liver disease is caused by cirrhosis, alcohol abuse, or obstructive jaundice.

### Claim 32 (depends on 28)

The method according to claim 28, wherein the liver disease is selected from the group consisting of hepatobiliary disease, hepatitis B, hepatitis C, liver cirrhosis, liver fibrosis, bile duct inflammation, and biliary obstruction.

### Claim 33 (depends on 28)

The method according to claim 28, wherein the composition is administered orally.

### Claim 34 (depends on 28)

The method according to claim 28, wherein the composition is administered topically to the mucosa of the gastro-intestinal tract.

### Claim 35 (depends on 34)

The method according to claim 34, wherein the composition further comprises a pharmaceutically acceptable (i) stabilizer, (ii) activator, (iii) carrier, (iv) permeator, (v) propellant, (vi) disinfectant, (vii) protectant, (viii) diluent, (ix) nutrient or (x) another excipients that promotes AP delivery to said gastro-intestinal tract.

### Claim 36 (depends on 28)

The method according to claim 28, wherein the LPS is detoxified, neutralized, or complexed in situ in the gastro-intestinal tract.