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Patent Searching and Data


Title:
COMPOSITIONS OF GALLIUM (III) COMPLEXES FOR ORAL ADMINISTRATION
Document Type and Number:
WIPO Patent Application WO/2018/146551
Kind Code:
A4
Abstract:
The present invention relates to oral dosage forms of GaQ3 derivatives with an enteric or delayed release coating, wherein said GaQ3 is admixed with a dispersant and in amorphous or nanoparticulate form. The preparation of said oral dosage forms is also disclosed. Such dosage forms are useful for the treatment of disease, including, but not limited to, cancer.

Inventors:
RHINEBARGER RICKEY (CA)
STETSKO GINA (CA)
Application Number:
PCT/IB2018/000213
Publication Date:
November 22, 2018
Filing Date:
February 09, 2018
Export Citation:
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Assignee:
ALTUM PHARMACEUTICALS INC (CA)
International Classes:
A61K31/47; A61K9/00; A61P35/00
Attorney, Agent or Firm:
SMART & BIGGAR (CA)
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Claims:
AMENDED CLAIMS

received by the International Bureau on 20 September 2018 (20.09.2018)

1. An oral dosage form which comprises GaQ3 including derivatives thereof protected by an enteric or delayed release coating, wherein said GaQ3 is in amorphous or nanoparticulate form , wherein said GaQ3 is admixed with a dispersant.

2. The oral dosage form of claim 1 wherein said encapsulated GaQ3 is contained in a capsule, tablet, microparticle or mini tablet.

3. The oral dosage form of claim 1, which when administered to dogs at a dose of GaQ3 of 10 mg/kg, provides a Cmax in plasma at least 100 times the Cmax in plasma of dogs administered 10 mg/kg of crystalline GaQ3.

4. The oral dosage form of claim 1, which when administered to dogs at a dose of GaQ3 of 10 mg/kg, provides an AUC in plasma at least 200 times the AUC in plasma of dogs administered 10 mg/kg of crystalline GaQ3.

5. The oral dosage form of claim 1, which when administered to dogs at a dose of GaQ3 of 10 mg/kg, provides a Cmax in plasma equivalent to 2336 ng/ml.

6. The oral dosage form of claim 1 , which when administered to dogs at a dose of GaQ3 of 10 mg/kg, provides an AUC in plasma equivalent to 60546 ng*hr/mL

7. The oral dosage form of claim 1 , which when administered to fasted female dogs at a dose of GaQ3 of 1 mg/kg, provides an AUC in plasma equivalent to 4381 ng*hr/niL

8. The oral dosage form of claim 1, which when administered to fasted male dogs at a dose of GaQ3 of 1 mg/kg, provides an AUC in plasma equivalent to 4227 ng*hr/ml.

9. The oral dosage form of claim 1, which when administered to fasted female dogs at a dose of GaQ3 of 1 mg/kg, provides provides a Cmax in plasma equivalent to 330 ng/ml.

10. The oral dosage form of claim 1, which when administered to fasted male dogs at a dose of GaQ3 of 1 mg/kg, provides provides a Cmax in plasma equivalent to 310 ng/ml.

11. The oral dosage formula of claim 1 wherein said dispersed GaQ3 maintains its amorphous or nanocrystalline state when exposed to water or to 75% relative humidity.

12. The oral dosage formula of claim 1 wherein said GaQ3 is amorphous or nanocrystalline tris (8-quinolinolato) gallium (III) in a 1 :1 wt/wt dispersion with Eudragit L- 100 and has the powder X-ray diffraction pattern (XRD) shown in Figure 1, curve A,

13. The oral dosage formula of claim 1 wherein the GaQ3 contained therein exhibits an immediate peak of dissolution when mixed with aqueous medium.

14. The oral dosage formula of claim 1 wherein the enteric or delayed release coating comprises shellac (esters of aleurtic acid), cellulose acetate phthalate (CAP), poly (methacrylic acid-co -methyl methacrylate), cellulose acetate trimellitate (CAT), polyvinyl acetate phthalate) (PVAP), hydroxypropyl methylcellulose phthalate (HPMCP), plant fibers, plastics, hydroxypropylmethylcellulose, hydroxypropylcellulose, methacrylic acid :

methacrylate copolymers, ammoalkyl methacrylate copolymers, cellulose acetate, triacetin, triethylcitrate, polyols such as glycerol, propylene glycol, polyethylene glycols PEG or organic esters such as phthalate esters (diethyl, dibutyl), citrate esters (triethyl, acetyl triethyl, acetyl tributyl), or oils/glycerides, acetylated monoglycerides or fractionated coconut oil or combinations thereof,

15. The oral dosage formula of claim 1 wherein the dispersant comprises gelatin, casein, lecithin, gum acacia, cholesterol, tragacanth, stearic acid, ben..alkonium chloride, calcium stearate. glyceryl monostearate, cetostearyl alcohol, cetomacrogol emulsifying wax, sorbitan esters, polyoxyethylene alkyl ethers, polyoxyethylene caster oil derivatives, polyoxyethylene sorbitan fatty acid esters, polyethyleneglycols, methacrylic acid : methacrylate copolymers, aminoalkyl methacrylate copolymers, polyoxyethylene stearates, colloidol silicon dioxide, phosphates, sodium dodecylsulfate, carboxy methylcellulose calcium, carboxymethylcellulose sodium, methylcellulose, hydroxyethylcellulose,

hydtoxypropylcellulose, hydioxypropylmethycellulose phthalate, noncrystalline cellulose, magnesium aluminum silicate, triethanolamine, polyvinyl alcohol, or polyvinylpyrrolidone or combinations thereof.

16, The oral dosage formula of claim 1 wherein the enteric or delayed release coating comprises a methacrylic acid : methacrylate copolymer.

17. The oral dosage formula of claim 15 wherein the dispersant comprises a methacrylic acid : methacrylate copolymer,

18, A method to administer a gallium complex to a subject which method comprises providing said subject with the formulation of claim 1.

19. The method of claim 18 wherein the subject is human or a laboratory animal model.

20. The method of claim 18 wherein the subject requires treatment for cancer.

21 , The method of claim 18 wherein the GaQ3 is tris (8-quinolinolato) gallium (III),