Macroporous Granules of Alkaline Earth Phosphates Using Cement Technology and Gas Evolving Porogen

Patent metadata

Field	Value
Publication number	US-2016279280-A1
Application number	US-201415038218-A
Country	US
Kind code	A1
Filing date	Nov 21, 2014
Priority date	Nov 21, 2013
Publication date	Sep 29, 2016
Grant date	—

Abstract

Macroporous cement compositions, methods of making the same, and methods of using the same, are described.

First claim

1 . A macroporous cement composition comprising a composition having pores made from a hydrogen-evolving process, wherein the pores range from about 100 μm to about 1 mm in size.

2 . The macroporous cement composition of claim 1 , wherein the hydrogen-evolving process is a reaction between a metal and water present in a liquid.

3 . The macroporous cement composition of claim 2 , wherein the metal is selected from the group consisting of magnesium, iron, and aluminum.

4 . (canceled)

5 . The macroporous cement composition of claim 3 , wherein the magnesium is in the form of spherical particles.

6 . The macroporous cement composition of claim 5 , wherein the magnesium particles are about 45 μm in diameter.

7 . The macroporous cement composition of claim 3 , wherein the magnesium is present in an alloy with one or more of Al, Zn, or a rare-earth metal.

8 . The macroporous cement composition of claim 1 , wherein the liquid further comprises silica.

9 . The macroporous cement composition of claim 1 , wherein the macroporous cement composition further comprises a biopolymer or polysaccharide.

10 . The macroporous cement composition of claim 9 , wherein the macroporous cement composition comprises alginate.

11 . The macroporous cement composition of claim 9 , wherein the macroporous cement composition comprises chitosan.

12 . The macroporous cement composition of claim 1 , wherein the macroporous cement composition comprises a post-microwaved powder comprised of a calcium phosphate that has been irradiated by microwaves.

13 . The macroporous cement composition of claim 1 , wherein the macroporous cement composition comprises a calcium phosphate selected from the group consisting of monetite, brushite, hydroxyapatite, tetracalcium phosphate, tricalcium phosphate, and octacalcium phosphate.

14 . The macroporous cement composition of claim 1 , wherein the macroporous cement composition comprises a magnesium phosphate.

15 . The macroporous cement composition of claim 1 , wherein the macroporous cement composition comprises a strontium-doped calcium phosphate or a strontium-doped magnesium phosphate.

16 . The macroporous cement composition of claim 1 , wherein the macroporous cement composition is configured to be injectable during the hydrogen-evolving process.

17 . The macroporous cement composition of claim 1 , further comprising drug molecules in the pores.

18 . The macroporous cement composition of claim 1 , further comprising an antibiotic.

19 . The macroporous cement composition of claim 18 , wherein the antibiotic is selected from the group consisting of: clindamycin, tigecycline, vancomycin, ciprofloxacin, ofloxacin, sulfamethoxazole, trimethoprim/sulfamethoxazole, amoxicillin, penicillin V, penicillin G, procaine penicillin, benzathine penicillin, carbencillin, mezlocillin, ampicillin, piperacillin, bacampicillin, tiearcillin, ticarcillin, piperacillin/tazobactam, aztreonam, cefotetan, loracarbef, mefoxin, merrem, levofloxacin, lomefioxacin, primaxim, cycloserine, kanamycin, dicloxacillin, demeclocycline, minocycline, doxycycline, oxytetracycline, tobramycin, gentamicin, neomycin, amikacin, craramyein, nebcin, erythromycin/sulfisoxazole, netromycin, streptomycin, tobramycin, cefotaxime, cefuroxime, cefazoline, ceffibuten, ceffizoxime, cefaclor, cefopoerazone, cefprozil, cefadroxil monohydrate, ceftazidime, trimethoprim/sulfamethoxazole, cephalexin, cefazolin, cefamandole nafate, cefepime, cefonicid, sulfadiazine, norfloxacin, enoxacin, cefdinir, seromycin, ceftriaxone, cefixime, ceftazidime, clarithromycin, dirithromycin, methenamine, ethionamide, trovafioxacin, sparfloxacin, interfon-α, indinavir, ganciclovir, foscamet, lamivudine, famciclovir, rimantadine, zalcitabine, interferon-β, indinavir, ganciclovir, saquinavir, ritonavir, ribavirin, erythromycin, troleandomycin, azithromycin, eliiidamycin, colistin, amphotericin B, flucytosine, fluconazole, griseofulvin, grepafloxacin, ultramicrosize griseofulvin, terbinafine, ketoconazole, clotrimazole, dapsone, delavirdine, ziduvudine, amantadine, palivizumab, valacyclovir, didanosine, nelfinavir, nevirapine, ribavirin, cidofovir, pyrimethamine, metronidazole, furazolidone, atovaquone, stavudine, lamiduvine, acyclovir, mionazole, nystatin, itraconazole, chloroquine, pyrimethamine, mefloquine, hydroxychloroquine, capreomycin, permethrin, crotamiton, lindane, fluoro-uracil, ethambutol, rifabutin, isoniazid, aminosalicyclic acid, rifapentine, pyrazinamide, coenzoyl peroxide, chlorhexidine gluconate, sodium oxychlorosene, benzoyl peroxide, rifampin, rifampin/isoniazid, rifampin/isoniazid/pyrazinamide, nitrofurantoin, linezolid, nitrofurantoin, fosfomycin, nalidixic acid, atropine, oxytetracycline/sulfamethizole/phenazopyridine, mupirocin, chloramphenical, neomycin/polymyxin, tfimetorpim/polythyxin, tobramycin/dexamethasone, vidatabine, ciprofloxacin, ofioxacin, sulfacetamide, mupirocin, povidoneodine, gentamicin, nystatin, chloramphenicol, bacitracin, sulconazole, terbinafine, tetrachlorosalicylanilide, metronidazole, metromdazole, ciclopiroxolamine, clotrimazole, clotrimazole/betamethasone, butenafine, clotrimazole, nattifine, oxiconazole, selenium, econazole, penciclovir, and pharmaceutically acceptable salts thereof.

20 . The macroporous cement composition of claim 1 , further comprising a growth factor.

21 . The macroporous cement composition of claim 20 , wherein the growth factor is selected from the group consisting of BMP1, BMP2, BMP3, BMP4, BMP5, BMP6, BMP7, BMP8a, BMP8b, BMP10, and BMP15.

22 . A cement composition comprising:
a powder component; a liquid component; and a porogen capable of reacting with the liquid component to produce a gas; wherein the powder component is mixed with the porogen and the liquid component to form a gaseous solution, the gaseous solution setting to form a hardened porous mass.

23 . A cement composition convertible by bodily processes into a macroporous cement composition of claim 1 .

24 . (canceled)

25 . (canceled)

26 . A method for making a cement composition comprising:
mixing a powder component with a liquid component and a metal to form a gaseous solution, wherein the metal is capable of reacting with water in a liquid to produce hydrogen gas; and allowing the gaseous solution to set into a hardened porous mass, wherein the hydrogen gas bubbles create pores in the hardened mass.

27 . A method for making a cement composition comprising:
mixing a powder component with a setting solution to form a paste; irradiating the paste with microwaves to form post-microwaved powder; mixing the post-microwaved powder with magnesium particles and a liquid to form hydrogen gas bubbles in a gaseous solution; and allowing the gaseous solution to set into a hardened porous mass, wherein the hydrogen gas bubbles create pores in the hardened porous mass.

28 . The method of claim 27 , wherein the liquid comprises silica.

29 . The method of claim 27 , wherein at least one of alginate or chitosan is mixed with the post-microwaved powder, magnesium particles, and liquid.

30 . The method of claim 27 , wherein the hardening of the paste occurs simultaneously with the production of hydrogen bubbles in the gaseous solution.

31 . The method of claim 27 , wherein the composition is configured go be extru

Assignees

• Univ Toledo

Inventors

• Bhaduri Sarit B
• Zhou Huan
• Agarwal Anand K
• Goel Vijay K
• Saleh Sameh

Classifications

• A61P31/04

  Antibacterial agents · CPC title

• A61K6/864

  Phosphate cements (apatite A61K6/838) · CPC title

• A61K6/86

  Al-cements · CPC title

• A61L27/047

  Other specific metals or alloys not covered by A61L27/042 - A61L27/045 or A61L27/06 · CPC title

• C04B2111/00836

  for medical or dental applications · CPC title