Method of treating protozoal gastrointestinal disorders by administering hyperimmune milk product

• US 5,106,618 A
• Filed: 05/22/1989
• Issued: 04/21/1992
• Est. Priority Date: 07/02/1987
• Status: Expired due to Term

• Current Assignee: Stolle Milk Biologics, Inc.
• Original Assignee: Stolle Research & Development Corporation
• Inventors: Beck, Lee R., Kotler, Donald P.
• Primary Examiner(s): Doll, John
• Assistant Examiner(s): Feisee, Lila
• Application Number:
  US07/355,786
• Time in Patent Office: 1,065 Days
• Field of Search: 424/85.8, 424/86, 424/87, 424/93, 424/95, 424/101, 424/88, 424/89, 514/2, 514/8, 514/21, 514/10, 514/12, 530/387, 530/388, 530/395
• US Class Current: 424/157.1
• CPC Class Codes: 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
• CPC Class Codes: C07K 16/04 from milk
• CPC Class Codes: C07K 16/12 against material from bacteria
• CPC Class Codes: Y10S 530/832 Milk; colostrum

Abstract

The invention comprises treatment of gastrointestinal disorders of parasitic protozoan and bacterial origin in immunocompromised and immunocompetent animals by administration hyperimmune milk products.

Claims

1. A method of treating cryptosporidiosis or isosporiasis in an immunocompromised animal which comprises:

administering to said immunocompromised animal a hyperimmune milk product containing a biologically active component which reduces the number of oocysts in the stool, reduces the number of Cryptosporidia or Isospora parasites in the intestine or alleviates the symptoms of cryptosporidiosis or isosporiasis in a subject infected with Cryptosporidia or Isospora from a hyperimmunized milk-producing mammal selected from the group consisting of cows, sheep, and goats, in amounts sufficient to treat said cryptosporidiosis or isosporiasis, wherein said hyperimmune milk product is selected from the group consisting of hyperimmune whole milk, hyperimmune whole milk fractions, and derivatives of hyperimmune whole milk which contain said biologically active component and is prepared by a process comprising;

(i) hyperimmunizing said milk-producing mammal with a mixture of non-protozoan bacterial antigens;

(ii) collecting milk from said milk-producing mammal after said milk-producing mammal reaches a hyperimmune state;

(iii) filtering said milk through a molecular sieve which excludes proteins of molecular weight greater than 100,000 daltons; and

(iv) testing the retentate of step (iii) for its ability to reduce the number of oocysts in the stool, reduce the number of Cryptosporidia or Isospora parasites in the intestine or alleviate symptoms of cryptosporidiosis or isosporiasis in a subject infected with Cryptosporidia or Isospora by administering to said subject the retentate of step (iii) and measuring the reduction of said oocysts, parasites, or symptoms.

3. The method of claim 1 wherein said immunocompromised animal is a human.

4. The method of claim 3 wherein said human comprises a human with acquired immunodeficiency syndrome.

5. The method of claim 1 wherein said hyperimmune milk product is in fluid form.

6. The method of claim 1 wherein said hyperimmune milk product is in solid form.

7. The method of claim 1 wherein said hyperimmune milk product is in concentrated form.

8. The method of claim 1 wherein after said collecting and prior to said filtering, said hyperimmune milk product is prepared by a process which comprises:

(i) pasteurizing said collected milk under low temperature at reduced pressure;

(ii) removing the fat from said milk.

9. The method of claim 8 wherein said retentate is concentrated greater than 10-fold.

10. The method of claim 1 wherein said milk-producing mammal is a bovid.

11. The method of claim 1 wherein said milk-producing animal is hyperimmunized by administration of a mixture of bacterial antigens comprising Stapholococcus aureus;

Stapholoccocus epidermidis;

Streptococcus pyogenes, A Type 1;

Streptococcus pyogenes, A. Type 3;

Streptococcus pyogenes, A. Type 5;

Streptococcus pyogenes, A. Type 8;

Streptococcus pyogenes, A. Type 12;

Streptococcus pyogenes, A. Type 14;

Streptococcus pyogenes, A. Type 18;

Streptococcus pyogenes, A. Type 22;

Aerobacter aerogenes;

Escherichia coli;

Pseudomonas aeruginosa;

Klebsiella pneumoniae;

Salmonella typhimurium;

Haemophilus influenzae;

Streptococcus mitis;

Proteus vulgaris;

Shigella dysenteriae;

Diplococcus pneumoniae;

Proprionibacter acnes Actinomyces (anaerobe);

Streptococcus mutans; and

Streptococcus agalactiae.

12. The method of claim 1 wherein said bacterial antigen is administered to said animal orally.

13. The method of claim 12 wherein said oral dose comprises 10⁶ to 10²⁰ cells.

14. The method of claim 1 wherein said bacterial antigen is administered parenterally.

15. The method of claim 1 wherein said bacterial antigen is administered by parenteral route in liquid form.

16. The method of claim 1 wherein said bacterial antigen is administered by parenteral route in microencapsulated form.

17. The method of claim 1 wherein said hyperimmune milk product is administered periodically to said subject.

18. The method of claim 7 wherein said periodic administration is by oral means.

19. The method of claim 17 wherein said periodic administration is by parenteral means.

20. The method of claim 17 wherein said periodic administration is by intranasal means.

21. The method of claim 17 wherein said periodic administration is by rectal means.

2. A method of treating cryptosporidiosis or isosporiasis in an AIDS patient which comprises:

orally administering to said AIDS patient a hyperimmune milk product from a hyperimmunized milk-producing bovid in amounts sufficient to treat said cryptosporidiosis or isosporiasis, wherein said hyperimmune milk product is prepared by a process comprising

i. intramuscularly hyperimmunizing said bovid with an injection of a microencapsulated slow-release vaccine wherein said vaccine comprises a mixture of nonprotozoan bacterial antigens selected from the group consisting of Staphylococcus aureus;

Staphylococcus epidermidis;

Streptococcus pyogenes, A. Type 1;

Streptococcus pyogenes, A. Type 3;

Streptococcus pyogenes, A. Type 5;

Streptococcus pyogenes, A. Type 8;

Streptococcus pyogenes, A. Type 12;

Streptococcus pyogenes, A. Type 14;

Streptococcus pyogenes, A. Type 18;

Streptococcus pyogenes, A. Type 22;

Aerobacter aerogenes;

Escherichia coli;

Pseudomonas aeruginosa;

Klebsiella pneumoniae;

Salmonella typhimurium;

Haemophilus influenzae;

Streptococcus mitis;

Proteus vulgaris;

Shigella dysenteriae;

Diplococcus pneumoniae;

Proprionibacter acnes Actinomyces (anaerobe);

Streptococcus mutans; and

Streptococcus agalactiae;

ii. collecting the milk from said bovid after said bovid reaches a hyperimmune state;

iii. pasteurizing said collected milk under low temperature at reduced pressure;

iv. removing the fat from said pasteurized milk;

v. filtering said defatted milk through molecular sieves which excludes proteins of molecular weight greater than 100,000; and

vi. concentrating the milk proteins in the retentate of said sieve approximately 30-fold prior to administration to said AIDS patient.