# US 5,344,822 A · Methods useful in endotoxin prophylaxis and therapy

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- Number: US 5,344,822 A
- Document ID: US5344822A
- Status: Granted
- Kind: A
- Application number: 07/928,930
- Filed: 1992-08-12
- Granted: 1994-09-06
- Earliest claimed: 1992-08-12
- Assignees: The Rogosin Institute
- Inventors: Daniel M. Levine; Thomas S. Parker; Albert L. Rubin
- Web page: https://patentgrep.com/patent/US5344822A

## CPC

- A61K 31/685: one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
- A61K 9/1275: Lipoproteins or protein-free species thereof, e.g. chylomicrons; Artificial high-density lipoproteins [HDL], low-density lipoproteins [LDL] or very-low-density lipoproteins [VLDL]; Precursors thereof
- A61P 3/06: Antihyperlipidemics
- A61P 39/02: Antidotes
- C07K 14/775: Apolipopeptides
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Treatment and prophylaxis of endotoxin caused toxicity is disclosed. This is accomplished by administering a lipid into which the endotoxin of concern is associated, preferably together with a peptide which is not an apolipoprotein. Preferably, the two components are administered in the form of a reconstituted particle, although this is by no means required.

## Claims

### Claim 1

Method for alleviating endotoxin caused toxicity in a subject comprising administering to a subject in need thereof an amount of (i) a peptide consisting of the amino acid sequence set forth in SEQ ID NO; 1 and (ii) a phosphatidylcholine, wherein (i) and (ii) are present in the form of an HDL like particle with which said endotoxin associates, in an amount sufficient to alleviate said toxicity.

### Claim 2 (depends on 1)

Method of claim 1, wherein said endotoxin is an E. coli endotoxin.

### Claim 3 (depends on 1)

Method of claim 1, wherein said endotoxin is an S. tymphimurium endotoxin.

### Claim 4

Method for alleviating endotoxin caused toxicity in a subject comprising administering to a subject in need thereof, separate and consecutive administrations of (i) a peptide consisting of the amino acid sequence f SEQ ID NO: 1 and (ii) a phosphatidylcholine with which said endotoxin associates, wherein (i) and (ii) are administered in an amount of each sufficient to alleviate said toxicity.

### Claim 5 (depends on 4)

Method of claim 4, wherein said endotoxin is an E. coli endotoxin.

### Claim 6 (depends on 4)

Method of claim 4, wherein said endotoxin is an S. typhimurium endotoxin.

### Claim 7

Method for reducing risk of endotoxin caused toxicity in a subject comprising administering to a subject who is to be subjected to exposure to an endotoxin an amount of (i) a peptide consisting of the amino acid sequence set forth in SEQ ID NO 1 and (ii) a phosphatidylcholine with which said endotoxin associates, wherein (i) and (ii) are present in the form of an HDL like particle, in an amount sufficient to reduce risk of endotoxin caused toxicity.