Formulas for diagnosing and treating hormone-dependent cancers and cancers of the organs responsible for steroid hormone synthesis

Patent metadata

Field	Value
Publication number	US-9707305-B2
Application number	US-201214349822-A
Country	US
Kind code	B2
Filing date	Sep 26, 2012
Priority date	Oct 5, 2011
Publication date	Jul 18, 2017
Grant date	Jul 18, 2017

Abstract

The present invention relates to a formulation of a therapeutic or diagnostic agent in the form of a nano-emulsion, to its preparation method and to the use of this formulation for treating or diagnosing hormone-dependent cancers or cancers of organs synthesizing steroidal hormones.

First claim

The invention claimed is:

1. A formulation of a therapeutic or diagnostic agent in the form of a nano-emulsion, comprising a continuous aqueous phase and at least one dispersed oily phase, wherein:
the oily phase comprises:
at least one amphiphilic lipid,
at least one solubilizing lipid,
at least one compound of the following formula (I):
(R-L) n -A  (I),

wherein :
n represents an integer from 1 to 5
L represents a simple bond or a divalent group selected from —O—, —COO—, —OOC—, —CO—NR′—, —NR′—CO—, —S—, —NR′—CO—NR′—, —O—CO—O—,
wherein R′ and R″ represent independently H or a linear or branched alkyl with 1 to 20 carbon atoms and
R represents a linear or branched alkyl comprising at least 11 carbon atoms or a linear or branched alkenyl comprising at least 11 carbon atoms, and
A represents a steriodic or sterolic group,

and
the aqueous phase includes at least one co-surfactant comprising at least one chain consisting of alkylene oxide units;

the proportion of the compound of formula (I) being from 0.05% to 3% by weight based on the weight of the dispersed oily phase, the weight of the dispersed oily phase including the weight of the co-surfactant.

2. The formulation of a therapeutic or diagnostic agent according to claim 1 , wherein the oily phase comprises at least one therapeutic agent for treating hormone-dependent cancers or cancers of organs synthesizing steroidal hormones, or one diagnostic agent.

3. The formulation of a therapeutic or diagnostic agent according to claim 1 , wherein the group A is a group having one of the following formulae:

wherein one or several of the carbon atoms are substituted with an -L-R group as defined in claim 1 .

4. The formulation of a therapeutic or diagnostic agent according to claim 1 , wherein L represents —O— or —COO—.

5. The formulation of a therapeutic or diagnostic agent according to claim 1 , wherein the amphiphilic lipid is a phospholipid.

6. The formulation of a therapeutic or diagnostic agent according to claim 1 , wherein the solubilizing lipid comprises at least one glyceride of fatty acids.

7. The formulation of a therapeutic or diagnostic agent according to claim 6 , wherein the solubilizing lipid comprises a mixture of saturated fatty acid glycerides including:
at least 10% by weight of C12 fatty acids,
at least 5% by weight of C14 fatty acids,
at least 5% by weight of C16 fatty acids, and
at least 5% by weight of C18 fatty acids.

8. The formulation of a therapeutic or diagnostic agent according to claim 1 , wherein the oily phase further includes at least one oil.

9. The formulation of a therapeutic or diagnostic agent according to claim 1 , wherein the co-surfactant includes at least one chain consisting of ethylene oxide or ethylene oxide and propylene oxide units.

10. The formulation of a therapeutic agent according to claim 1 , comprising a therapeutic agent for treating hormone-dependent cancers or cancers of organs synthesizing steroidal hormones selected from the group consisting of:
agonists of gonadotropin releasing hormone,
antagonists of aromatase,
anti-estrogens, and
anti-androgens.

11. The formulation of a diagnostic agent according to claim 1 , wherein the diagnostic agent is selected from the group consisting of a liphophilic fluorophore, fatty acid analogs, phospholipids functionalized with a fluorescent group, amphiphilic derivatives of dialkylcarbocyanines, fluorescent probes derived from sphingolipids, steroids or lipopolysaccharides, amphiphilic derivatives of cyanines, rhodamines, fluoresceins or cumarins, and diphenylhexatriene and its derivatives.

12. A method for preparing a formulation of a therapeutic or diagnostic agent in the form of a nano-emulsion according to claim 1 , comprising at least one continuous aqueous phase and at least one dispersed oily phase, comprising:
(i) preparing the oily phase comprising at least one solubilizing lipid, at least one amphiphilic lipid, optionally at least one therapeutic or diagnostic agent and at least one compound of formula (I);
(ii) preparing an aqueous phase comprising a polyalkoxylated co-surfactant;
(iii) dispersing the oily phase in the aqueous phase under the action of sufficient shearing for forming a nano-emulsion; and
(iv) recovering the thereby formed nano-emulsion.

13. A therapeutic treatment method for hormone-dependent cancers, or cancers of organs synthesizing steroidal hormones comprising administering to a mammal in need thereof a therapeutically effective amount of the formulation of a therapeutic agent according to claim 1 .

14. A method for diagnosing hormone-dependent cancers or cancers of organs synthesizing steroidal hormones comprising administering to a subject a formulation of a diagnostic agent according to claim 1 .

15. The formulation of a therapeutic agent according to claim 10 , comprising a therapeutic agent for treating hormone-dependent cancers or cancers of organs synthesizing steroidal hormones selected from the group consisting of estrogen, progestins, Formestane, Exemestane, Aminoglutethimide, Anastrozole, Fadrozole, Letrozole, Megestrol acetate, Medroxyprogesterone acetate, Mifepristone, Tamoxifene, Fulvestrant, abiraterone acetate and cyproterone acetate.

16. The formulation of a diagnostic agent according to claim 11 , wherein the diagnostic agent is indocyanine green or 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindodicarbocyanine perchlorate.

17. The therapeutic treatment method according to claim 13 , wherein the method is used to treat breast cancer, prostate cancer, cancer of the ovaries, or cancer of the adrenal glands.

18. The method for diagnosing according to claim 14 , wherein the method is used to diagnose breast cancer, prostate cancer, cancer of the ovaries, or cancer of the adrenal glands.

Assignees

• Commissariat L Energie Atomique Et Aux Energies Alternatives
• Commissariat Energie Atomique

Inventors

• Merian Juliette
• Boisgard Raphaël
• Tavitian Bertrand
• Texier-Nogues Isabelle

Classifications

• A61K51/122

  Microemulsions, nanoemulsions · CPC title

• A61K31/565

  not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol · CPC title

• A61K9/1075

  Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers (A61K9/0026 takes precedence) · CPC title

• G01N33/743

  Steroid hormones · CPC title

• G01N2333/723

  Steroid/thyroid hormone superfamily, e.g. GR, EcR, androgen receptor, oestrogen receptor · CPC title