Growth-promoting and immunizing subcutaneous implant

• US 20060252049A1
• Filed: 05/04/2005
• Published: 11/09/2006
• Est. Priority Date: 05/04/2005
• Status: Abandoned Application

• Current Assignee: Ivy Animal Health, Inc. (Elanco Animal Health, Inc.)
• Original Assignee: Ivy Animal Health, Inc. (Elanco Animal Health, Inc.)
• Inventors: Shuler, Richard O., Cravens, Ronald
• Application Number:
  US11/121,535
• Publication Number:
  US 20060252049A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 2039/552 Veterinary vaccine
• CPC Class Codes: A61K 39/02 Bacterial antigens
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: C12N 2770/24334 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Abstract

The present invention relates generally to an implant for use in animals. More particularly, the present invention relates to an implant including a pharmaceutical agent and a biological agent for use in animals to promote growth, regulate metabolism and prevent illness or disease. A method for promoting growth and immunity in animal using an implant including a pharmaceutical agent and a biological agent. The implant is preferably administered to an animal subcutaneously.

Claims

1. A growth-promoting and immunizing implant for use in animals comprising:

an effective amount of at least one biological agent; and

an effective amount of at least one pharmaceutical agent.

2. The implant of claim 1, said effective amount of said biological agent being from about 1-100% by weight of said implant.

3. The implant of claim 1, said effective amount of said biological agent being from about 50-99% by weight of said implant.

4. The implant of claim 1, said effective amount of said biological agent being from about 60-75% by weight of said implant.

5. The implant of claim 1, wherein said biological agent is a compound that stimulates an immune response in an animal.

6. The implant of claim 5, wherein said biological agent is selected from the group consisting of vaccines, bacterins, toxoids, bacterin-toxoids, and mixtures thereof.

7. The implant of claim 6, wherein said biological agent is selected from the group consisting of infectious bovine rhinotracheitis virus, bovine viral diarrhea virus, bovine parainfluenza 3 virus, bovine respiratory syncytial virus, Haemophilus somnus, Mannheimia haemolytica, Pasteurella multocida, Leptospira spp., Campylobacterfetus, Clostridium spp., rotavirus, coronavirus, Escherichia coli, Moraxella bovis, Bordetella bronchiseptica, Erysipelothrix rhusiopathiae, Actinobacillus pleuropneumoniae, Mycoplasma hyopneumoniae, Mycoplasma bovis, Mycoplasma dispar, porcine respiratory reproductive syndrome virus, porcine parvovirus, transmissible gastroenteritis virus, pseudorabies virus, Salmonella spp., Lawsonia ssp., Coccidia spp., Anaplasma spp., Babbesia spp., canine parvovirus, canine adenovirus, canine distemper, canine parainfluenza, rabies, feline leukemia, feline vital rhinotracheitis, feline calivirus, feline panleukopenia, Chlamydia psittaci, combinations and mixtures thereof.

8. The implant of claim 1, said effective amount of said pharmaceutical agent being from about 1-100% by weight of said implant.

9. The implant of claim 1, said effective amount of said pharmaceutical agent being from about 50-99% by weight of said implant.

10. The implant of claim 1, said effective amount of said pharmaceutical agent being from about 60-75% by weight of said implant.

11. The implant of claim 1, wherein said pharmaceutical agent is selected from the group consisting of parasiticides, pesticides, germicides, biocides, fungicides, insecticides, antioxidants, growth promotants, growth inhibitors, disinfectants, sterilization agents, catalysts, nutrients, vitamins, steroid hormones, prostaglandins, antibiotics, anti-inflammatory agents, chemotherapeutic agents, cardiovascular agents, antihypertensive agents, estrus suppressors, fertility promotors, somatotropins, gonadotropins, and mixtures thereof.

12. The implant of claim 11, wherein said parasiticide is selected from the group consisting of polyketide ivermectins, milbemycins, milbemycin oximes, fenbendazole, oxfendazole, luferon, and mixtures thereof.

13. The implant of claim 11, wherein said growth promotant is selected from the group consisting of progesterone, estradiol, estradiol benzoate, trenbolone acetate, zeranol, derivatives thereof, and mixtures thereof.

14. The implant of claim 11, wherein said antibiotic is selected from the group consisting of macrolide antibiotics, penicillin, tetracycline, derivatives thereof, and mixtures thereof.

15. The implant of claim 14, wherein said antibiotic is selected from the group consisting of tylosin, tylosin tartrate, oxytetracycline, neomycin, tilmicosin phosphate, ceftiofur hydrochloride, ceftiofur sodium, sulfadimethoxine, derivatives thereof, and mixtures thereof.

16. The implant of claim 11, wherein said antibiotic is selected from the group consisting of bacteriostats, anti-inflammatory agents, and mixtures thereof.

17. The implant of claim 11, wherein said steroid hormone is selected from the group consisting of levonorgestrel, estradiol 17β

, testosterone, testosterone propionate, ethynyl estradiol, derivatives thereof, and mixtures thereof.

18. The implant of claim 11, wherein said estrus suppressor is selected from the group consisting of melengesterol acetate, norgestomet, derivatives thereof, and mixtures thereof.

19. The implant of claim 1, wherein said pharmaceutical agent is an inorganic or organic macromolecular bioactive agent.

20. The implant of claim 19, wherein said bioactive agent is selected from the group consisting of acetylcholine esterase inhibitors, aminoglycocides, angiotensin-converting enzyme inhibitors, antiarrhythmics, antibacterial agents, anticancer agents, antidepressants, antidiabetics, antiepileptics, anti-viral agents, antihistamines, antihypertensives, antinauseants, antiprostaglandins, antirheumatics, antiseptics, barbiturates, beta-blockers, betalactamase inhibitors, calcium channel blockers, cardiac glycosides, cephalosporins, immune reagents, immunostimulators, immuno-suppressives, liposaccharide complexing agents, methylxanthines, minerals, O-beta-hydroxyethylated rutins, propxyphenes, salicyclates, tetracyclin compounds, vasodilators, acetaminiophen, acetazolamide, acetophenetidin, achromycine hydrochloride, bendofluazide, benzthiozide, betamethasone, calcium and salts, thereof including, leucovorin calcium, carbamazepine, clindamycin, chlorpropamide, chlorothalidone, chlorothiazide, clofibrate, cortisone acetate, cyclopenthiazide, dexamethazone, dextroamphetamine sulphate, diclofenac sodium, dioxin, dimethindene and salts thereof, diprophylline, disopyramide and salts thereof, dipyrone, doxycycline, fenbufen, fenoprofen, ferrous fumarate, flurbiprofen, frusemide, furosemide, glibenclamide, haloperidol, hydralazine, hydrochloride hydrochlorothiazide, hydroflumethiazide ibuprofen, indomethacin, indoprofen, iron salts, kanamycin, ketoprofen, L-Dopa, lithium salts, metaclopramide, methazolamide, methotrexate, fluoro-uracil, methotrexate sodium, methyl Dopa, metronidazole, minocyclin hydrochloride, mofebutazone, morphine, naproxen, nifedipine, oxyphenbutazone, penicillin, peridinol and salts thereof, phenylbutazone, phenobarbital, phenylpropanolamine, phenytoin, pindolol, piroxicam, pirprofen, potassium chloride, prazosin, propanolol, proxyphilline, pyrvinium emboate, quinidine, reserpine, salicylamide, salicyl salicyclic acid, sodium fluoride, spironolactone, sulfadiazine, sulfamerazine, tetracyclin compounds, tolbutamide, trihexylphenidyl hydrochloride, triethoprim, valproic acid, vancomycin, zoxazolamine, carbonic anhydrase inhibitors, anti-glaucoma agents, benzalkonium chloride, benzocaine, amilorid, hypnotics, sedatives, psychic energizers, tranquillizers, anticonvulsants, muscle relaxants, anti-Parkinson agents, analgesics, steroidal anti-inflammatories, anti-autoimmune agents, local and systemic anesthetics, contraceptives, sympathomimetrics, parasympathomimetrics, lipid regulating agents, anti-androgenics, antiparasitics, neoplastics, anti-AIDS agents, mutagens, teratogens, hypoglycaemic, nutritionals, fats, ophthalmics, otolaryngolmics, electrolytes, diagnostic agents, diuretics, nonsteroidal anti-inflammatories, antihistamines, chlomethazine, clemastine, hydroxyzine, terfenadine promethazine, astemizole, loratadine, mast cell stabilizers, bronchodilators, isoetharine hydrochloride, theophylline, albuterol, epinedrine, norepinedrine, adrenaline, noradrenaline, corticosteroids, prednisolone, hydrocortisone, cortisone acetate, flunisolide and triamincinolone acetate, anti cholesterol agents, estradiol, progesterones, testosterone, amino acids, thyroxine, peptides, histamines, fatty acids and fatty acid derivatives, inositol phosphates, gamma-aminobutyric acid, ketone bodies, acetylcholine, protein, DNA, carbohydrates, immunoglobulins G, M, A, D and E and their fragments and sub-chains, hormones, somatotropins, growth hormones, somatomedins, erythromycin, adrenocorticotropic hormone (ACTH), parahormone, follicle stimulating hormone, inhibin, renin, leuteinizing hormone, thyroid stimulating hormone, hypothalamic releasing hormones, TSH releasing factor, gastrointestinal hormones, vasopressin (ADH), somatostatin, immunomodulators, immunostimulators, immunoinhibitors colony stimulating factors (CSF), growth factors, cell chemotactic factors, antihemophilic factors, surface receptors and co-receptors, mineral oils, detergents, surfactants, derivatives thereof, and mixtures thereof.

21. The implant of claim 1 further comprising from about 0.1-50% by weight of an excipient.

22. The implant of claim 21, wherein said excipient is selected from the group consisting of starch, talc, glucose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, calcium stearate, sodium stearate fumarate, stearic acid, sodium lauryl sulfonate, sodium stearate, glycerol monostearate, sodium chloride, polyethylene glycol, polyoxyethylene, glycerol behenate, hydrogenated vegetable oils, magnesium stearate, precipitated or fumed silicas, soidum starch glycolates, calcium phosphate, caldium carbonate, dextrins, polyvinyl pyrrolidone, polylactic acid, magnesium aluminum silicates, cellulose and its derivatives, especially ethylcellulose and microcrystalline cellulose, sodium carboxymethylcellulose, lactose, dried skim milk, derivatives thereof, and mixtures thereof.

23. The implant of claim 1 further comprising from about 0.1-50% by weight of an additive selected from the group consisting of inert and functional fillers, glidants, disintegrants, lubricants, adjuvants, antibiotic preservatives, polymeric supports, binders, coloring agents, and mixtures thereof.

24. The implant of claim 1 wherein said implant is a single pellet.

25. The implant of claim 1 wherein said implant comprises at least one discrete biological agent pellet and at least one discrete pharmaceutical agent pellet.

26. The implant of claim 24 wherein said pellet is selected from the group consisting of immediate release formulations, sustained release formulations, and mixtures thereof.

27. The implant of claim 25 wherein said discrete pellets are independently selected from the group consisting of immediate release formulations, sustained release formulations, and mixtures thereof.

28. The implant of claim 1 wherein said implant is suitable for subcutaneous implantation, vaginal administration, nasal administration, or sublingual administration.

29. The implant of claim 1 wherein said implant is suitable for subcutaneous implantation in an animal'"'"'s ear.

30. A method for promoting growth in and/or immunizing animals comprising the steps of:

providing an implant including an effective amount of at least one biological agent, and an effective amount of at least one pharmaceutical agent;

administering said implant to an animal.

31. The method of claim 30, said effective amount of said biological agent being from about 1-100% by weight of said implant.

32. The method of claim 30, said effective amount of said biological agent being from about 50-99% by weight of said implant.

33. The method of claim 30, said effective amount of said biological agent being from about 60-75% by weight of said implant.

34. The method of claim 30, wherein said biological agent is a compound that stimulates an immune response in an animal.

35. The method of claim 34, wherein said biological agent is selected from the group consisting of vaccines, bacterins, toxoids, bacterin-toxoids, and mixtures thereof.

36. The method of claim 35, wherein said biological agent is selected from the group consisting of infectious bovine rhinotracheitis virus, bovine viral diarrhea virus, bovine parainfluenza 3 virus, bovine respiratory syncytial virus, Haemophilus somnus, Mannheimia haemolytica, Pasteurella multocida, Leptospira spp., Campylobacterfetus, Clostridium spp., rotavirus, coronavirus, Escherichia coli, Moraxella bovis, Bordetella bronchiseptica, Erysipelothrix rhusiopathiae, Actinobacillus pleuropneumoniae, Mycoplasma hyopneumoniae, Mycoplasma bovis, Mycoplasma dispar, porcine respiratory reproductive syndrome virus, porcine parvovirus, transmissible gastroenteritis virus, pseudorabies virus, Salmonella spp., Lawsonia ssp., Coccidia spp., Anaplasma spp., Babbesia spp., canine parvovirus, canine adenovirus, canine distemper, canine parainfluenza, rabies, feline leukemia, feline vital rhinotracheitis, feline calivirus, feline panleukopenia, Chlamydia psittaci, combinations and mixtures thereof.

37. The method of claim 30, said effective amount of said pharmaceutical agent being from about 1-100% by weight of said implant.

38. The method of claim 30, said effective amount of said pharmaceutical agent being from about 50-99% by weight of said implant.

39. The method of claim 30, said effective amount of said pharmaceutical agent being from about 60-75% by weight of said implant.

40. The method of claim 30, wherein said pharmaceutical agent is selected from the group consisting of parasiticides, pesticides, germicides, biocides, fungicides, insecticides, antioxidants, growth promotants, growth inhibitors, disinfectants, sterilization agents, catalysts, nutrients, vitamins, steroid hormones, prostaglandins, antibiotics, anti-inflammatory agents, chemotherapeutic agents, cardiovascular agents, antihypertensive agents, estrus suppressors, fertility promotors, somatotropins, gonadotropins, and mixtures thereof.

41. The method of claim 40, wherein said parasiticide is selected from the group consisting of polyketide ivermectins, milbemycins, milbemycin oximes, fenbendazole, oxfendazole, luferon, and mixtures thereof.

42. The method of claim 40, wherein said growth promotant is selected from the group consisting of progesterone, estradiol, estradiol benzoate, trenbolone acetate, zeranol, derivatives thereof, and mixtures thereof.

43. The method of claim 40, wherein said antibiotic is selected from the group consisting of macrolide antibiotics, penicillin, tetracycline, derivatives thereof, and mixtures thereof.

44. The method of claim 43, wherein said antibiotic is selected from the group consisting of tylosin, tylosin tartrate, oxytetracycline, neomycin, tilmicosin phosphate, ceftiofur hydrochloride, ceftiofur sodium, sulfadimethoxine, derivatives thereof, and mixtures thereof.

45. The method of claim 40, wherein said antibiotic is selected from the group consisting of bacteriostats, anti-inflammatory agents, and mixtures thereof.

46. The method of claim 40, wherein said steroid hormone is selected from the group consisting of levonorgestrel, estradiol 17β

, testosterone, testosterone propionate, ethynyl estradiol, derivatives thereof, and mixtures thereof.

47. The method of claim 40, wherein said estrus suppressor is selected from the group consisting of melengesterol acetate, norgestomet, derivatives thereof, and mixtures thereof.

48. The method of claim 30, wherein said pharmaceutical agent is an inorganic or organic macromolecular bioactive agent.

49. The method of claim 48, wherein said bioactive agent is selected from the group consisting of acetylcholine esterase inhibitors, aminoglycocides, angiotensin-converting enzyme inhibitors, antiarrhythmics, antibacterial agents, anticancer agents, antidepressants, antidiabetics, antiepileptics, anti-viral agents, antihistamines, antihypertensives, antinauseants, antiprostaglandins, antirheumatics, antiseptics, barbiturates, beta-blockers, betalactamase inhibitors, calcium channel blockers, cardiac glycosides, cephalosporins, immune reagents, immunostimulators, immuno-suppressives, liposaccharide complexing agents, methylxanthines, minerals, O-beta-hydroxyethylated rutins, propxyphenes, salicyclates, tetracyclin compounds, vasodilators, acetaminiophen, acetazolamide, acetophenetidin, achromycine hydrochloride, bendofluazide, benzthiozide, betamethasone, calcium and salts, thereof including, leucovorin calcium, carbamazepine, clindamycin, chlorpropamide, chlorothalidone, chlorothiazide, clofibrate, cortisone acetate, cyclopenthiazide, dexamethazone, dextroamphetamine sulphate, diclofenac sodium, dioxin, dimethindene and salts thereof, diprophylline, disopyramide and salts thereof, dipyrone, doxycycline, fenbufen, fenoprofen, ferrous fumarate, flurbiprofen, frusemide, furosemide, glibenclamide, haloperidol, hydralazine, hydrochloride hydrochlorothiazide, hydroflumethiazide ibuprofen, indomethacin, indoprofen, iron salts, kanamycin, ketoprofen, L-Dopa, lithium salts, metaclopramide, methazolamide, methotrexate, fluoro-uracil, methotrexate sodium, methyl Dopa, metronidazole, minocyclin hydrochloride, mofebutazone, morphine, naproxen, nifedipine, oxyphenbutazone, penicillin, peridinol and salts thereof, phenylbutazone, phenobarbital, phenylpropanolamine, phenytoin, pindolol, piroxicam, pirprofen, potassium chloride, prazosin, propanolol, proxyphilline, pyrvinium emboate, quinidine, reserpine, salicylamide, salicyl salicyclic acid, sodium fluoride, spironolactone, sulfadiazine, sulfamerazine, tetracyclin compounds, tolbutamide, trihexylphenidyl hydrochloride, triethoprim, valproic acid, vancomycin, zoxazolamine, carbonic anhydrase inhibitors, anti-glaucoma agents, benzalkonium chloride, benzocaine, amilorid, hypnotics, sedatives, psychic energizers, tranquillizers, anticonvulsants, muscle relaxants, anti-Parkinson agents, analgesics, steroidal anti-inflammatories, anti-autoimmune agents, local and systemic anesthetics, contraceptives, sympathomimetrics, parasympathomimetrics, lipid regulating agents, anti-androgenics, antiparasitics, neoplastics, anti-AIDS agents, mutagens, teratogens, hypoglycaemic, nutritionals, fats, ophthalmics, otolaryngolmics, electrolytes, diagnostic agents, diuretics, nonsteroidal anti-inflammatories, antihistamines, chlomethazine, clemastine, hydroxyzine, terfenadine promethazine, astemizole, loratadine, mast cell stabilizers, bronchodilators, isoetharine hydrochloride, theophylline, albuterol, epinedrine, norepinedrine, adrenaline, noradrenaline, corticosteroids, prednisolone, hydrocortisone, cortisone acetate, flunisolide and triamincinolone acetate, anti cholesterol agents, estradiol, progesterones, testosterone, amino acids, thyroxine, peptides, histamines, fatty acids and fatty acid derivatives, inositol phosphates, gamma-aminobutyric acid, ketone bodies, acetylcholine, protein, DNA, carbohydrates, immunoglobulins G, M, A, D and E and their fragments and sub-chains, hormones, somatotropins, growth hormones, somatomedins, erythromycin, adrenocorticotropic hormone (ACTH), parahormone, follicle stimulating hormone, inhibin, renin, leuteinizing hormone, thyroid stimulating hormone, hypothalamic releasing hormones, TSH releasing factor, gastrointestinal hormones, vasopressin (ADH), somatostatin, immunomodulators, immunostimulators, immunoinhibitors colony stimulating factors (CSF), growth factors, cell chemotactic factors, antihemophilic factors, surface receptors and co-receptors, mineral oils, detergents, surfactants, derivatives thereof, and mixtures thereof.

50. The method of claim 30 further comprising from about 0.1-50% by weight of an excipient.

51. The method of claim 50, wherein said excipient is selected from the group consisting of starch, talc, glucose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, calcium stearate, sodium stearate fumarate, stearic acid, sodium lauryl sulfonate, sodium stearate, glycerol monostearate, sodium chloride, polyethylene glycol, polyoxyethylene, glycerol behenate, hydrogenated vegetable oils, magnesium stearate, precipitated or fumed silicas, soidum starch glycolates, calcium phosphate, caldium carbonate, dextrins, polyvinyl pyrrolidone, polylactic acid, magnesium aluminum silicates, cellulose and its derivatives, especially ethylcellulose and microcrystalline cellulose, sodium carboxymethylcellulose, lactose, dried skim milk, derivatives thereof, and mixtures thereof.

52. The method of claim 30 further comprising from about 0.1-50% by weight of an additive selected from the group consisting of inert and functional fillers, glidants, disintegrants, lubricants, adjuvants, antibiotic preservatives, polymeric supports, binders, coloring agents, and mixtures thereof.

53. The method of claim 30 wherein said implant is a single pellet.

54. The method of claim 30 wherein said implant comprises at least one discrete biological agent pellet and at least one discrete pharmaceutical agent pellet.

55. The method of claim 53 wherein said pellet is selected from the group consisting of immediate release formulations, sustained release formulations, and mixtures thereof.

56. The method of claim 54 wherein said discrete pellets are independently selected from the group consisting of immediate release formulations, sustained release formulations, and mixtures thereof.

57. The method of claim 30 wherein said administering step is selected from the group consisting of subcutaneous implantation, vaginal administration, nasal administration, or sublingual administration.

58. The method of claim 30 wherein said administering step is subcutaneous implantation in an animal'"'"'s ear.