AU2001269701A1 - Method for treatment and prevention of mastitis - Google Patents
Method for treatment and prevention of mastitisInfo
- Publication number
- AU2001269701A1 AU2001269701A1 AU2001269701A AU2001269701A AU2001269701A1 AU 2001269701 A1 AU2001269701 A1 AU 2001269701A1 AU 2001269701 A AU2001269701 A AU 2001269701A AU 2001269701 A AU2001269701 A AU 2001269701A AU 2001269701 A1 AU2001269701 A1 AU 2001269701A1
- Authority
- AU
- Australia
- Prior art keywords
- oxazolidinone
- administration
- mammal
- lactoferrin
- mastitis
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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- 238000000034 method Methods 0.000 title claims description 37
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- 230000002265 prevention Effects 0.000 title claims description 12
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims description 87
- 235000021242 lactoferrin Nutrition 0.000 claims description 44
- 241000124008 Mammalia Species 0.000 claims description 37
- 102000010445 Lactoferrin Human genes 0.000 claims description 32
- 108010063045 Lactoferrin Proteins 0.000 claims description 32
- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 claims description 32
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- 150000003839 salts Chemical class 0.000 claims description 11
- 208000015181 infectious disease Diseases 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- TYZROVQLWOKYKF-ZDUSSCGKSA-N linezolid Chemical compound O=C1O[C@@H](CNC(=O)C)CN1C(C=C1F)=CC=C1N1CCOCC1 TYZROVQLWOKYKF-ZDUSSCGKSA-N 0.000 claims description 8
- 238000002347 injection Methods 0.000 claims description 6
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- FNDDDNOJWPQCBZ-ZDUSSCGKSA-N sutezolid Chemical compound O=C1O[C@@H](CNC(=O)C)CN1C(C=C1F)=CC=C1N1CCSCC1 FNDDDNOJWPQCBZ-ZDUSSCGKSA-N 0.000 claims description 6
- 230000001225 therapeutic effect Effects 0.000 claims description 6
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- 101000798100 Bos taurus Lactotransferrin Proteins 0.000 claims description 4
- 229940072440 bovine lactoferrin Drugs 0.000 claims description 4
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- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
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- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
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- WQVJHHACXVLGBL-GOVYWFKWSA-N polymyxin B1 Polymers N1C(=O)[C@H](CCN)NC(=O)[C@@H](NC(=O)[C@H](CCN)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)CCCC[C@H](C)CC)CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1CC1=CC=CC=C1 WQVJHHACXVLGBL-GOVYWFKWSA-N 0.000 description 1
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 1
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Description
METHOD FOR TREATMENT AND PREVENTION OF MASTITIS BACKGROUND OF THE INVENTION
1. Field of the Invention The present invention relates to the treatment and prevention of mastitis with known oxazolidinones, alone or in combination with exogenous lactoferrins.
2. Description of the Related Art Mastitis, which has been known and treated for many years, is an inflammatory disease of the mammary gland of a mammal caused by infection of a multitude of bacteria. Bovine mastitis is one of the most difficult cattle diseases to deal with and is of considerable economic significance to the dairy industry. Bovine mastitis may be caused by Gram-negative bacteria such as Escherichia coli and Klebsiella spp, as well as Gram-positive bacteria such as Staphylcoccus aureus and Streptococcus agalactiae. The primary treatment for bovine mastitis so far has been the administration of antibiotics such as penicillin. However, the antibiotic therapies currently available for bovine mastitis do not always work, partly because these antibiotics are effective only against Gram-positive pathogens but have poor or strain- dependent activity against Gram-negative pathogens. Thus, there is clearly a need for more effective treatment for mastitis.
The oxazolidinones in the present invention are disclosed in, e.g., US Pat. Nos. 5,688,792 and 6,040,306 and International Publication WO 98/54161, none of which discloses the use of oxazolidinones for treating or preventing mastitis.
Lactoferrin, a glycoprotein present in mammary gland secretions and many other exocrine secretions of mammals, is well known to those skilled in the art. The increased concentrations of endogenous lactoferrin in milk during dry period and the bacteriostatic or bactericidal effects of exogenous lactoferrins are disclosed. See, for example, Smith KL and Oliver SP, Exp. Med. Biol. 137:535-554 (1981); Lohuis, J.A.C.M., Hesen, SM, and Beers H, pages 110-111 in Proc. 3rd. Int. IDF Mastitis Sem., Tel Aviv, Israel, A. Saran and S. Soback, ed. M. Lachmann Printers LTD., Haifa, Israel (1995). None of these documents disclose the use of lactoferrin for treating or preventing mastitis.
Under in vitro conditions lactoferrin may enhance the antimicrobial effect of antibiotics against strains of Salmonellae and Escherichia coli. See, for example, A. S. Naidu and R. R. Arnold, Diagn. Microbiol. Infect. Dis 20:69-75 (1994); M. S.
Sanchez and J. L. Watts, J Dairy Sci. 82: 494-499 (1999). Such enhancing effect of lactoferrins is, however, antibiotic specific. For example, lactoferrins can enhance the antimicrobial effect of erythromycin, ampicillin, ciprofloxacin, chloramphenicol, and rifampicin, but not cefalexin, gentamycin, or polymycin B, against Salmonellae. (A. S. Naidu and R. R. Arnold, Diagn. Microbiol. Infect. Dis 20:69-75 (1994). Thus, none of the prior art teaches or even suggests that lactoferrins may enhance the anti-mastitis effect of the oxazolidinones as disclosed in the present invention.
SUMMARY OF INVENTION It has been surprisingly found that oxazolidinone is effective in treating and preventing mastitis caused by Gram-negative, as well as by Gram-positive, pathogens in mammals. It has also been surprisingly found that the anti-mastitis effect of oxazolidinone is enhanced by lactoferrins. The oxazolidinones in the present invention are disclosed in, e.g., U.S. Pat. Nos. 5,688,792 and 6,040,306 and International Publication WO 98/54161, none of which discloses the use of oxazolidinones for treating or preventing mastitis. The disclosure of each of U.S. Pat. Nos. 5,688,792 and 6,040,306 and International Publication WO 98/54161 is incorporated here by reference.
Disclosed is a method of treating or preventing mastitis in a mammal, comprising administration to said mammal during dry period of an therapeutically effective amount of an oxazolidinone selected from the group consisting of (S)-N-[[3- [3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide and N- [[(5S)-3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-l,3-oxazolidin-5- yl]methyl]acetamide and pharmaceutically acceptable salts thereof.
Also disclosed is a method of treating or preventing mastitis in a mammal, comprising administration to said mammal of an therapeutically effective amount of an oxazolidinone selected from the group consisting of (S)-N-[[3-[3-fluoro-4-(4- morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide and N-[[(5S)-3-[3- fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-l,3-oxazolidin-5-yl]methyl]acetamide and pharmaceutically acceptable salts thereof, in combination with intramammary administration of a lactoferrin in an amount effective to enhance the therapeutic effect of the oxazolidinone.
Further disclosed is a composition for use in the treatment or prevention of mastitis in a mammal, comprising
(a) an oxazolidinone selected from (S)-N-[[3-[3-fluoro-4-(4-mo holinyl)phenyl]-2- oxo-5-oxazolidinyl]methyl]acetamide and N-[[(5S)-3-[3-fluoro-4-(4- thiomorpholinyl)phenyl]-2-oxo- 1 ,3-oxazolidin-5-yl]methyl]acetamide or pharmaceutically acceptable salts thereof, and (b) a lactoferrin at an amount effective to enhance the therapeutic effect of said oxazolidinone.
DETAILED DESCRIPTION OF THE INVENTION In one embodiment the invention is directed to a method of treating or preventing mastitis in a mammal comprising administering to said mammal a therapeutically effective amount of an oxazolidinone. In another embodiment the invention is directed to a method of treating or preventing mastitis in a mammal comprising administering to said mammal a therapeutically effective amount of an oxazolidinone in combination with administration of an exogenous lactoferrin at amount effective to enhance the therapeutic effect of the oxazolidinone. Li a preferred embodiment the present invention is directed to a method of treating or preventing conform mastitis in a cow by intramammary infusion of an oxazolidinone during the dry period. These and other embodiments of the present invention will readily occur to those of ordinary skill in the art in view of the disclosure therein.
The following description of the invention concerns mainly with dairy cows; however, it is to be understood that the invention is contemplated with the treatment and prevention of mastitis in all types of mammals.
The oxazolidinones in the present invention are disclosed in, e.g., US Pat. Nos. 5,688,792 and 6,040,306 and International Publication WO 98/54161. Examples of suitable oxazolidinones include (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo- 5-oxazolidinyl]methyl]acetamide and N-[[(5S)-3-[3-fluoro-4-(4- thiomorpholinyl)phenyl]-2-oxo- 1 ,3-oxazolidin-5-yl]methyl]acetamide, and pharmaceutically acceptable salts thereof.
The active agents of the subject invention can be given to a mammal either after the onset of mastitis, thus serving as a treatment, or prior to the onset of mastitis, thus serving as a preventive measure. The preventive use of the subject invention is particularly important, for instance, in case mastitis has been detected in some animals in the same herd. It is often desirable to treat all animals in same herd affected in order to eliminate the infection from the whole herd.
Regardless of whether the oxazolidinones are used to treat or prevent mastitis, the oxazolidinones can either be used individually, in combination with each other, or in combination with exogenous lactoferrins. When used during the dry period, the oxazolidinones are preferred to be administered without exogenous lactoferrins. When used during lactation period, the oxazolidinones are preferred to be administered in combination with the administration of exogenous lactoferrins.
Regardless of whether or not lactoferrins are administered, the oxazolidinones are administered either intramammarily or systemically. Intramammary administration, however, is the preferred route when the oxazolidinones are administered in combination with lactoferrins.
When administered intramammarily, the oxazolidinones are administered by injection into the mammary gland, typically by infusion into the teat through the milk canal. The dosage of the oxazolidinones by intramammary injection is from about 25 mg to about 1000 mg, and preferably from about 125 mg to about 500 mg. The oxazolidinones are typically given once.
When administered systemically, the oxazolidinones are administered parenterally or orally, and typically once per day for three or more consecutive days.
When administered orally, the oxazolidinones can be administered in tablet, capsule or liquid (suspension or solution) dosage form in a pharmaceutically acceptable vehicle. The oxazolidinones can also be administered in feed or drinking water. Oral administration in any of these dosage forms is well known in the art and may be carried out in ways common in the animal veterinary medical art. Regardless of the dosage form, the anti-mastitis effective amount of the oxazolidinones is from about 1 mg/kg/day to about 10 mg/kg/day, and preferably from about 2.5 mg/kg/day to about 5 mg/kg/day.
When administered parenterally, the oxazolidinones are administered by subcutaneous, intradermal, intramuscular, or intravenous injection. Parenteral administration is well known in the art and may be carried out in ways common in the animal veterinary or human medical art. When prepared as injectables, the oxazolidinones are usually prepared as liquid formulations in a pharmaceutically acceptable vehicle as is known to those skilled in the art. Regardless of the route, the daily dosage of the oxazolidinones by patrenteral administration is from about 1
mg/kg/day to about 10 mg/kg/day, and preferably from about 2.5 mg/kg/day to about 5 mg/kg/day.
The exact dosage and frequency duration of administration of the oxazolidinones may be changed in response to numerous variables such as the particular oxazolidinone used, the severity of the condition being treated, the general physical condition of the animal, the response of the animal to the treatment, the size of the animal, and whether lactoferrin is used and the dosage thereof.
When lactoferrin is used in combination with the oxazolidinones, the lactoferrin should be administered via intramammary injection, typically by infusion into the teat through the milk canal, and in the same frequency and duration as the oxazolidinones.
Lactoferrin is formulated as a liquid dosage form (solution or suspension) in a pharmaceutically acceptable vehicle as is known to those skilled in the art, and is preferably formulated together with the oxazolidinone as a liquid dosage form (solution or suspension) in a composite formulation.
In another embodiment, the invention is directed to a composition for use in the treatment or prevention of mastitis in a mammal, comprising (a) an oxazolidinone and (b) a lactoferrin at an amount effective to enhance the therapeutic effect of said oxazolidinone. The composition should be prepared in liquid dosage forms in any pharmaceutically acceptable carriers as are known in the art. The composition is preferably administered by intramammary injection.
When formulated together with the oxazolidinone in a composite formulation, the lactoferrin is administered simultaneously with the oxazolidinones. When formulated separately from the oxazolidinones, the lactoferrin is typically administered within 1 hour of the oxazolidinone administration. The amount of lactoferrin effective to enhance the anti-mastitis effect of the oxazolidinones is from about 0.5 g to about 5 gram, and preferably from about 2 g to about 3 g, regardless of the size and species of the animal being treated. The exact dosage and frequency and duration of administration of the lactoferrin may be changed in response to numerous variables, such as the particular oxazolidinone used and the dosage thereof, the severity of the condition being treated, the general physical condition of the animal, the response of the animal to the treatment, and levels of endogenous lactoferrins.
DEFINITIONS AND CONVENTIONS
The definitions and explanations below are for the terms as used throughout this entire document including both the specification and the claims.
DEFINITIONS A "therapeutically effective amount" of oxazolidinones refers to any amount of the oxazolidinones, administered either individually, in combination with each other or with lactoferrin, that is sufficient to either treat or prevent mastitis in a mammal to which the oxazolidinones are administered.
"Pharmaceutically acceptable" refers to those properties and/or substances which are acceptable to the animal from a pharmacological/toxicological point of view and to the manufacturing pharmaceutical chemist from a physical/chemical point of view regarding composition, formulation, stability, animal tolerance and bioavail- ability.
"Oxazolidinones" refer to the compounds of EXAMPLES 1 and 2. "Treating mastitis" refers to ameliorating an animal that has contacted mastitis.
"Preventing mastitis" refers to suppressing the occurrence, severity, and duration of mastitis if it is later contacted.
"Dry period" refers to the time period during which the mammal is non- lactating. EXAMPLES
Without further elaboration, it is believed that one skilled in the art can, using the preceding description, practice the present invention to its fullest extent. The following detailed examples describe how to practice the invention and are to be construed as merely illustrative, and not limitations of the preceding disclosure in any way whatsoever. EXAMPLE 1
(S)-N-[[3-[3-fluoro-4-(4-morpholinyl)ρhenyl]-2-oxo-5- oxazolidinyl]methyl]acetamide EXAMPLE 2 (2) N-[[(5S)-3-[3-fluoro-4-(4-thiomorρholinyl)phenyl]-2-oxo-l,3-oxazolidin-
5-yI]methyl]acetamide. EXAMPLE 3
A 3-lactation cow in dry period with moderate mastitis is administered 300 mg of the oxazolidinone in EXAMPLE 1, once per day for 5 days. The oxazolidinone is formulated as a solution and administered by intramammary infusion. At the end of the treatment the cow is examined and the mastitis is gone. EXAMPLE 4
A 2-lactation cow without mastitis is administered a single dose of 250 mg of the oxazolidinone in EXAMPLE 2 at the start of dry off period. The oxazolidinone is formulated as a solution and administered by intramammary infusion. Although mastitis occurs in other dry cows that are in the same herd but are not treated with the oxazolidinones, the cow treated is not infected. EXAMPLE 5
A 3-lactation cow in lactation with moderate mastitis is administered 300 mg of the oxazolidinone in EXAMPLE 2 in combination with administration of 3 g of bovine lactoferrin, once per day for 5 consecutive days. The oxazolidinone and the lactoferrin are prepared in a composite suspension formulation and administered by intramammary infusion. At the end of the treatment the cow is examined and the mastitis is gone.
Claims
1. A method of treating or preventing mastitis in a mammal, comprising administration to said mammal during dry period of an therapeutically effective amount of an oxazolidinone selected from the group consisting of (S)-N-[[3-[3- fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide and N- [[(5S)-3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-l,3-oxazolidin-5- yl]methyl]acetamide and pharmaceutically acceptable salts thereof.
2. The method of claim 1 wherein said administration is done prior to the onset of the infection.
3. The method of claim 1 wherein said administration is done after the onset of the infection.
4. The method of claim 1 wherein the mastitis is caused by Escherichia coli.
5. The method of claim 1 wherein the mammal is a cow, goat, or ewe.
6. The method of claim 5 wherein the mammal is a cow.
7. The method of claim 1 wherein the administration of the oxazolidinone is via intramammary injection.
8. The method of claim 7 wherein the oxazolidinone is administered at an amount from about 25 mg to about 1000 mg.
9. The method of claim 8 wherein the oxazolidinone is administered at an amount from about 125 mg to about 500 mg.
10. The method of claim 1 wherein the administration of the oxazolidinone is done systemically.
11. The method of claim 10 wherein the daily dose of the oxazolidinone is from about 1 mg/kg to about 10 mg/kg.
12. The method of claim 11 wherein the daily dose of the oxazolidinone is from about 2.5 mg/kg to about 5 mg/kg.
13. The method of claim 1 wherein the administration of the oxazolidinone is during dry period.
14. A method of treating or preventing mastitis in a mammal, comprising administration to said mammal of an therapeutically effective amount of an oxazolidinone selected from the group consisting of (S)-N-[[3-[3-fluoro-4-(4- morpholinyl)phenyl] -2-oxo-5-oxazolidinyl]methylJacetamide and N- [[(5S )-3 - [3 - fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo- 1 ,3-oxazolidin-5-yl]methyl]acetamide and pharmaceutically acceptable salts thereof, in combination with intramammary administration of a lactoferrin in an amount effective to enhance the therapeutic effect of the oxazolidinone.
15. The method of claim 14 wherein the lactoferrin is a bovine lactoferrin.
16. The method of claim 14 wherein the administration of both the oxazolidinone and lactoferrin is done prior to the onset of the infection.
17. The method of claim 14 wherein the administration of both the oxazolidinone and lactoferrin is done after the onset of the infection.
18. The method of claim 14 wherein the mastitis is caused by Escherichia coli.
19. The method of claim 14 wherein the mammal is a cow, goat, or ewe.
20. The method of claim 14 wherein the mammal is a cow.
21. The method of claim 14 wherein the administration of the oxazolidinone is via intramammary injection.
22. The method of claim 21 wherein the amount of oxazolidinone to be administered is from about 25 mg to about 1000 mg.
23. The method of claim 21 wherein the amount of the oxazolidinone to be administered is from about 125 mg to about 500 mg.
24. The method of claim 14 wherein the administration of the oxazolidinone is done systemically.
25. The method of claim 24 wherein the daily dose of the oxazolidinone to be administered is from about 1 mg/kg/day to about 10 mg/kg/day.
26. The method of claim 24 wherein the daily dose of the oxazolidinone to be administered is from about 2.5 mg/kg/day to about 5 mg/kg/day.
27. The method of claim 14 wherein the amount of lactoferrin to be administered , is from about 0.5 g to about 5 g.
28. The method of claim 14 wherein the amount of lactoferrin to be administered is from about 2 g to about 3 g.
29. The method of claim 14 wherein the administration of both the oxazolidinone and the lactoferrin is done during dry period.
30. The method of claim 14 wherein the administration of both the oxazolidinone and the lactoferrin is done during lactation period.
31. A composition for use in the treatment or prevention of mastitis in a mammal, comprising (a) an oxazolidinone selected from (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2- oxo-5-oxazolidinyl]methyl]acetamide and N-[[(5S)-3-[3-fluoro-4-(4- thiomorpholinyl)phenyl]-2-oxo- 1 ,3-oxazolidin-5-yl]methyl]acetamide or pharmaceutically acceptable salts thereof, and (b) a lactoferrin at an amount effective to enhance the therapeutic effect of said oxazolidinone.
32. The composition of claim 31 wherein said lactoferrin is a bovine lactoferrin.
33. Use of an oxazolidinone for the manufacture of a medicament for administration to a mammal for the treatment or prevention of mastitis, wherein said oxazolidinone is selected from (S)-N-[[3-[3-fluoro-4-(4-moφholinyl)phenyl]-2-oxo- 5-oxazolidinyl]methyl]acetamide and N-[[(5S)-3-[3-fluoro-4-(4- thiomorpholinyl)phenyl]-2-oxo- 1 ,3-oxazolidin-5-yl]methyl]acetamide and pharmaceutically acceptable salts thereof.
34. Use of an oxazolidinone for the manufacture of a medicament for administration to a mammal combined with a lactoferrin for the treatment or prevention of mastitis, wherein said oxazolidinone is selected from (S)-N-[[3-[3- fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide and N- [ [(5 S)-3- [3-fluoro-4-(4-thiomorpholinyl)phenyl] -2-oxo- 1 ,3-oxazolidin-5 - yl]methyl]acetamide and pharmaceutically acceptable salts thereof.
35. The use according to claim 33 or 34 wherein said medicament is for administration to the mammal during dry period.
36. The use according to claim 33 or 34 wherein said medicament is for administration to the mammal during lactation period.
37. The use according to claim 33 or 34 wherein said medicament is for administration to the mammal prior to the onset of the infection.
38. The use according to claim 33 or 34 wherein said medicament is for administration to the mammal after the onset of the infection.
39. The use according to claim 33 or 34 wherein said medicament is for intramammary administration.
40. The use according to claim 33 or 34 wherein said medicament is for systemic administration.
41. Use of a lactoferrin for the treatment or prevention of mastitis for intramammary administration to a mammal receiving concomitantly an oxazolidinone selected from (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]acetamide and N-[[(5S)-3-[3-fluoro-4-(4- thiomorpholinyl)phenyl]-2-oxo-l,3-oxazolidin-5-yl]methyl]acetarnide and pharmaceutically acceptable salts thereof.
42. Use of a lactoferrin for the manufacture of a medicament for the treatment or prevention of mastitis for intramammary administration to a mammal receiving concomitantly an oxazolidinone selected from (S)-N-[[3-[3-fluoro-4-(4- morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide and N-[[(5S)-3-[3- fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-l,3-oxazolidin-5-yl]methyl]acetamide and pharmaceutically acceptable salts thereof.
43. The use according to claim 41 or 42 wherein said medicament is for administration prior to the onset of the infection.
44. The use according to claim 41 or 42 wherein said medicament is for administration after the onset of the infection.
45. The use according to claim 41 or 42 wherein said lactoferrin is a bovine lactoferrin.
46. The use according to claim 33, 34, 41 or 42 wherein the mastitis is caused by Escherichia coli.
47. The use according to claim 33, 34, 41 or 42 wherein the mammal is a cow, goat, or ewe.
48. The use of claim 47 wherein the mammal is a cow.
49. Use of the compounds disclosed herein to prepare a medicament for the treatment or prevention of mastitis in a mammal.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US21590000P | 2000-07-05 | 2000-07-05 | |
| US60/215,900 | 2000-07-05 | ||
| PCT/US2001/016496 WO2002002121A2 (en) | 2000-07-05 | 2001-06-25 | Method for treatment and prevention of mastitis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2001269701A1 true AU2001269701A1 (en) | 2002-04-11 |
| AU2001269701B2 AU2001269701B2 (en) | 2005-10-27 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2001269701A Ceased AU2001269701B2 (en) | 2000-07-05 | 2001-06-25 | Method for treatment and prevention of mastitis |
| AU6970101A Pending AU6970101A (en) | 2000-07-05 | 2001-06-25 | Method for treatment and prevention of mastitis |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU6970101A Pending AU6970101A (en) | 2000-07-05 | 2001-06-25 | Method for treatment and prevention of mastitis |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US6562820B2 (en) |
| EP (1) | EP1299106A2 (en) |
| JP (1) | JP2004501973A (en) |
| AR (1) | AR029557A1 (en) |
| AU (2) | AU2001269701B2 (en) |
| CA (1) | CA2410476A1 (en) |
| NZ (1) | NZ523448A (en) |
| PE (1) | PE20020236A1 (en) |
| WO (1) | WO2002002121A2 (en) |
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|---|---|---|---|---|
| JP3597491B2 (en) * | 2001-06-27 | 2004-12-08 | 株式会社ティーセル研究所 | Mammary gland immunostimulant and lactating method in lactating cows |
| EP2138171A1 (en) * | 2008-06-18 | 2009-12-30 | Istituto Superiore Di Sanita' | Veterinarian compositions containing terpinen-4-ol for the treatment and prevention of mastitis |
| CN102271696A (en) * | 2008-12-04 | 2011-12-07 | 梅里亚有限公司 | Intramammary teat sealant |
| NZ600269A (en) | 2009-05-20 | 2014-02-28 | Dec Int Nz Ltd | Delivery device for treatment of mastitis |
| RU2547550C1 (en) * | 2013-12-26 | 2015-04-10 | Государственное научное учреждение Всероссийский научно-исследовательский ветеринарный институт патологии, фармакологии и терапии Российской академии сельскохозяйственных наук (ГНУ ВНИВИПФиТ Россельхозакадемии) | Method of treatment of mastitis in lactating sheep |
| BR112017022768B1 (en) | 2015-04-24 | 2022-05-17 | Sanuwave, Inc | Acoustic pressure shock wave applicator |
| JP2018127399A (en) * | 2015-06-17 | 2018-08-16 | 共立製薬株式会社 | Therapeutic agent and treatment method for cattle acute or acute mastitis during lactation |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5688792A (en) | 1994-08-16 | 1997-11-18 | Pharmacia & Upjohn Company | Substituted oxazine and thiazine oxazolidinone antimicrobials |
| MY115155A (en) | 1993-09-09 | 2003-04-30 | Upjohn Co | Substituted oxazine and thiazine oxazolidinone antimicrobials. |
| NZ501412A (en) | 1997-05-30 | 2001-11-30 | Upjohn Co | Oxazolidinone antibacterial agents having a thiocarbonyl functionality |
| US6040306A (en) | 1997-11-18 | 2000-03-21 | Pharmacia & Upjohn Company | Method of treating psoriasis, arthritis and reducing the toxicity of cancer chemotherapy |
| KR20010015910A (en) | 1998-01-23 | 2001-02-26 | 로렌스 티. 마이젠헬더 | Oxazolidinone Combinatorial Libraries, Compositions and Methods of Preparation |
| MY122454A (en) | 1998-06-05 | 2006-04-29 | Upjohn Co | Use of oxazolidinones for the preparation of a medicament for transdermal delivery |
| HUP0102836A3 (en) | 1998-07-14 | 2003-12-29 | Upjohn Co | Use of oxazolidinones for preparation of pharmaceutical compositions suitable for treating eye infections |
-
2001
- 2001-06-23 US US09/888,634 patent/US6562820B2/en not_active Expired - Fee Related
- 2001-06-25 EP EP01948228A patent/EP1299106A2/en not_active Withdrawn
- 2001-06-25 WO PCT/US2001/016496 patent/WO2002002121A2/en not_active Ceased
- 2001-06-25 AU AU2001269701A patent/AU2001269701B2/en not_active Ceased
- 2001-06-25 NZ NZ523448A patent/NZ523448A/en unknown
- 2001-06-25 CA CA002410476A patent/CA2410476A1/en not_active Abandoned
- 2001-06-25 JP JP2002506743A patent/JP2004501973A/en active Pending
- 2001-06-25 AU AU6970101A patent/AU6970101A/en active Pending
- 2001-07-03 AR ARP010103174A patent/AR029557A1/en unknown
- 2001-07-03 PE PE2001000660A patent/PE20020236A1/en not_active Application Discontinuation
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