Methods and Compositions Related to PLUNC Surfactant Polypeptides

• US 20090110756A1
• Filed: 11/02/2007
• Published: 04/30/2009
• Est. Priority Date: 11/02/2006
• Status: Active Grant

• Current Assignee: University of Iowa Research Foundation
• Original Assignee: University of Iowa Research Foundation
• Inventors: McCray, Paul B. JR., Bartlett, Jennifer, Ramaswamy, Subramanian, Gakhar, Lokesh, Mallampalli, Rama K.
• Granted Patent: US 7,951,781 B2
• Time in Patent Office: Days
• US Class Current: 424/718
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/43 Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula , e.g. penicillins, penems
• CPC Class Codes: A61K 31/66 Phosphorus compounds
• CPC Class Codes: A61K 31/685 one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/395 Alveolar surfactant peptides; Pulmonary surfactant peptides
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system

Abstract

Embodiments include compositions and methods for lower the surface tension of a liquid-air interface by contacting such interface with all or part of a PLUNC polypeptide.

Claims

1. A method of lowering surface tension at a liquid-air interface comprising administering an amount of an isolated PLUNC polypeptide sufficient to lower the surface tension at the liquid-air interface.

2. The method of claim 1, wherein the PLUNC polypeptide is an amino terminal fragment of a PLUNC protein.

3. The method of claim 2, wherein the amino terminal fragment has an amino acid sequence of 10 to 200 amino acids of the amino terminal sequence of SEQ ID NO:

2, SEQ ID NO;

4, SEQ ID NO;

6, SEQ ID;

8, SEQ ID NO;

10, SEQ ID NO;

12, or SEQ ID NO;

14.

4. The method of claim 1, wherein PLUNC polypeptide is administered at a dose of 1 μ

g to 100 mg per kg of body weight.

5. The method of claim 1, wherein the liquid-air interface is part of the respiratory system or auditory system of a subject.

6. The method of claim 5, wherein the liquid-air interface is present in a subject'"'"'s upper respiratory system, trachea, mouth, or lungs.

7. The method of claim 5, wherein the liquid-air interface is present in a subject'"'"'s Eustachian tubes.

8. The method of claim 5, wherein administration is by endotracheal administration.

9. The method of claim 5, wherein administration is by inhalation.

10. The method of claim 5, further comprising a second therapy.

11. The method of claim 10, wherein the second therapy is a respiratory therapy.

12. The method of claim 11, wherein the respiratory therapy is conventional ventilation, high frequency ventilation, or continuous positive airway pressure.

13. The method of claim 10, wherein the second therapy is administration of one or more therapeutic agents.

14. The method of claim 13, wherein the other therapeutic agents are nitric oxide, steroids, antioxidants, vitamins, vitamin derivatives, reactive oxygen scavengers, bronchodilators, diuretics, antimicrobial agents, anti-infective agents, anti-hypertensive agents or anti-inflammatory agents.

15. The method of claim 1, comprising administering a pulmonary surfactant.

16. The method of claim 15, wherein the pulmonary surfactant is Poractant Alfa, Beractant, Bovactant, Colfosceril Palmitate, Surfactant-Ta, Calfactant, Pumactant, Lusupultide or Sinapultide.

17. The method of claim 10, wherein the second therapy is an antibiotic therapy.

18. The method of claim 17, wherein the antibiotic therapy comprises administration of penicillin, ampicillin, amoxycillin, vancomycin, cycloserine, bacitracin, cephalolsporin, imipenem, colistin, methicillin, streptomycin, kanamycin, tobramycin, gentamicin, tetracycline, chlortetracycline, doxycycline, chloramphenicol, lincomycin, clindamycin, erythromycin, oleandomycin, polymyxin nalidixic acid, rifamycin, rifampicin, gantrisin, trimethoprim, isoniazid, paraminosalicylic acid, or ethambutol.

19. A method of enhancing effectiveness of anti-microbial agents comprising administering a PLUNC polypeptide having an amino acid sequence of SEQ ID NO:

2, SEQ ID NO;

4, SEQ ID NO;

6, SEQ ID;

8, SEQ ID NO;

10, SEQ ID NO;

12, or SEQ ID NO;

14 and an anti-microbial, wherein the PLUNC polypeptide lowers the surface tension of a liquid-air interface and enhances dispersion of the anti-microbial.

20. The method of claim 19, wherein the PLUNC polypeptide is an amino terminal fragment of a PLUNC polypeptide having an amino acid sequence of 10 to 200 amino acids of the amino terminal sequence of SEQ ID NO:

2, SEQ ID NO;

4, SEQ ID NO;

6, SEQ ID;

8, SEQ ID NO;

10, SEQ ID NO;

12, or SEQ ID NO;

14.

21. A method of enhancing effectiveness of a surfactant comprising administering a PLUNC polypeptide having an amino acid sequence of SEQ ID NO:

2, SEQ ID NO;

4, SEQ ID NO;

6, SEQ ID;

8, SEQ ID NO;

10, SEQ ID NO;

12, SEQ ID NO;

14, or an amino acid sequence of 10 to 200 amino acids of the amino terminal sequence thereof and a surfactant, wherein the PLUNC polypeptide lowers the surface tension of a liquid-air interface produced by the surfactant alone.

22. A surfactant composition comprising a PLUNC surfactant and a second surfactant.

23. The surfactant composition of claim 22, wherein the second surfactant is a lipid.

24. The surfactant of claim 23 wherein the lipid component is phosphatidylcholines, phospatidylglycerols, phosphatidylethanolamines, phosphatidylserines, phosphatidic acids, phosphatidylinositols, sphingolipids, diacylglycerides, cardiolipin, ceramides, cerebrosides

25. The surfactant of claim 24, wherein the phospholipids is dipalmitoyl phosphatidylcholine (DPPC), dilauryl phosphatidylcholine (DLPC) (C12:

0), dimyristoyl phosphatidylcholine (DMPC) (C14;

0), distearoyl phosphatidylcholine (DSPC), diphytanoyl phosphatidylcholine, nonadecanoyl phosphatidylcholine, arachidoyl phosphatidylcholine, dioleoyl phosphatidylcholine (DOPC) (C18;

1), dipalmitoleoyl phosphatidylcholine (C 16;

1), linoleoyl phosphatidylcholine (C18;

2), myristoyl palmitoyl phosphatidylcholine (MPPC), steroyl myristoyl phosphatidylcholine (SMPC), steroyl palmitoyl phosphatidylcholine (SPPC), palmitoyloleoyl phosphatidylcholine (POPC), palmitoyl palmitooleoyl phosphatidylcholine (PPoPC), dipalmitoyl phosphatidylethanolamine (DPPE), palmitoyloleoyl phosphatidylethanolamine (POPE), dioleoylphosphatidylethanolamine (DOPE), dimyristoyl phosphatidylethanolamine (DMPE), distearoyl phosphatidylethanolamine (DSPE), dioleoyl phosphatidylglycerol (DOPG), palmitoyloleoyl phosphatidylglycerol (POPG), dipalmitoyl phosphatidylglycerol (DPPG), dimyristoyl phosphatidylglycerol (DMPG), distearoyl phosphatidylglycerol (DSPG), dimyristoylphosphatidylserine (DMPS), distearoylphosphatidylserine (DSPS), palmitoyloleoyl phosphatidylserine (POPS), soybean lecithin, egg yolk lecithin, sphingomyelin, phosphatidylinositols, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidic acids, egg phosphatidylcholine (EPC) or combinations thereof.

26. The surfactant of claim 24, wherein the lipid is DPPC.