# US 5,352,462 A · Anti-inflammatory factor, method of isolation, and use

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- Number: US 5,352,462 A
- Document ID: US5352462A
- Status: Granted
- Kind: A
- Application number: 07/966,741
- Filed: 1992-10-27
- Granted: 1994-10-04
- Earliest claimed: 1982-06-03
- Assignees: Stolle Research & Development Corporation
- Inventors: Lee R. Beck
- Web page: https://patentgrep.com/patent/US5352462A

## CPC

- A23C 9/20: Dietetic milk products not covered by groups A23C9/12 - A23C9/18
- A24B 15/30: by organic substances {(A24B15/281 takes precedence)}
- A61K 9/1647: {Polyesters, e.g. poly(lactide-co-glycolide)}
- A61K 35/20: Milk; Whey; Colostrum
- A61K 39/39508: {from milk, i.e. lactoglobulins}
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 2317/11: isolated from eggs
- A23C: DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; PREPARATION THEREOF (preservation thereof A23B11/00)
- A24B: MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
- 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)

## Abstract

The invention relates to an anti-inflammatory factor isolated from milk and to methods for using this factor to remove adhered neutrophils from endothelial cells, to prevent the emigration of cells from the vasculature and to suppress the response of lymphocytes to foreign antigens.

## Claims

### Claim 1

A composition comprising an anti-inflammatory factor, in purified form, wherein:
a) said factor is present in the whey of pasteurized skimmed milk;
b) said factor occurs in both aggregated and non-aggregated form;
c) the percentage of said factor present in aggregated form increases as the salt concentration of said composition decreases;
d) both the aggregated and non-aggregated forms of said factor have anti-inflammatory activity;
e) the molecular weight of said factor in non-aggregated form is less than about 10,000 daltons as determined by ultrafiltration;
f) said factor carries a negative charge at pH 7.0 as determined by its binding characteristics to ion exchange columns;
g) said factor is not a peptide or protein;
h) said factor is not inactivated when boiled for 30 minutes; and
i) said factor binds to a chromatography medium having an affinity for cis hydroxyl groups when such binding takes place in 0.25M ammonium acetate at pH 7.0 and detaches from said medium in 0.1M formic acid at pH 2.8.

### Claim 2 (depends on 1)

A method for inhibiting neutrophils from adhering to endothelial cells in a mammal, wherein said method comprises administering to said mammal the composition of claim 1 at a dose sufficient to inhibit said adherence.

### Claim 3 (depends on 1)

A method for detaching neutrophils which have adhered to endothelial cells in a mammal, wherein said method comprises administering to said mammal the composition of claim 1 at a dose sufficient to cause said detachment.

### Claim 4 (depends on 3)

The method of claim 3, wherein said neutrophils have adhered to said endothelial cells in response to platelet activating factor.

### Claim 5 (depends on 1)

A method for inhibiting the interaction between CD18 cell-surface antigens present in a mammal and molecules which are capable of binding to said antigens, wherein said method comprises administering the composition of claim 1 to said mammal at a dose sufficient to inhibit said interaction.

### Claim 6 (depends on 1)

A method for inhibiting the emigration of leukocytes from the venous system of a mammal, wherein said method comprises administering the composition of claim 1 to said mammal at a dose sufficient to inhibit said emigration.

### Claim 7 (depends on 6)

The method of claim 6, wherein said leukocytes are neutrophils.

### Claim 8 (depends on 1)

A method for suppressing the mitogenic response of lymphocytes in a host mammal to foreign antigens, wherein said method comprises administering the composition of claim 1 to said mammal at a dose sufficient to suppress said mitogenic response.

### Claim 9 (depends on 8)

The method of claim 8, wherein said antigens are on the surface of cells.

### Claim 10 (depends on 9)

The method of claim 9, wherein said cells are leukocytes.

### Claim 11 (depends on 9)

The method of claim 9, wherein said cells are lymphocytes.