Poly(methylidene malonate) microspheres, preparation method and pharmaceutical compositions containing them

Microspheres having an average diameter of between 1 μm and 100 μm comprising a continuous network of a supports material, in which a substance is dispersed, said network being selected from the group consisting of a dense network and a network incorporating a dispersed aqueous phase, said support material contains at least 70% by weight of a homopolymer comprising recurring units of a general formula (I):

• in which:
• R1 represents a radical selected from the group consisting of an alkyl group having 1 to 6 carbon atoms and a (CH2)m —COOR3 group in which m is an integer of between 1 and 5 and R3 represents an alkyl group having 1 to 6 carbon atoms;
• ad R2 represents an alkyl group having 1 to 6 carbon atoms;
• and
• n is an integer of between 1 and 5;
• said homopolymer having a molecular weight of 1,000 to 100,000.

A method of preparing microspheres having an average diameter of between 1μm and 100 μm, constituted of a continuous network of a support material, said network incorporating a dispersed aqueous phase;

• said support material containing at least 70% by weight of a homopolymer constituted of recurring units of the following general formula (I):
• in which:
• R1 represents a radical selected from the group consisting of an alkyl group having 1 to 6 carbon atoms and a (CH2)m —COOR3 group in which m is an integer of between 1 and 5 and R3 represents an alkyl group having 1 to 6 carbon atoms;
• R2 represents an alkyl group having 1 to 6 carbon atoms;
• and
• n is an integer of between 1 and 5;
• said homopolymer having a molecular weight of 1,000 to 100,000,
• comprising the steps of:
• a) preparing a first solution of the polymer comprising the support material in a volatile organic solvent;
• b) preparing a second solution non-miscible with the solution obtained in step a);
• c) preparing a first emulsion by dispersing the second solution in the first solution, the solution of polymer forming a continuous phase;
• d) preparing a second emulsion either by dispersing, with agitation, the first emulsion obtained in step c) in a dispersing medium non-miscible with said first emulsion, or by pouring with agitation, into said first emulsion, a solution comprising a medium non-miscible with said first emulsion;
• and
• e) evaporating said organic solvent with agitation.

A method of preparing microspheres having an average diameter of between 1μm and 100μm, constituted of a continues network of a support material, said network incorporating a dispersed aqueous phase;

• said support material containing at least 70% by weight of a homopolymer constituted of recurring units of the following general formula (I):
• in which:
• R1 represents a radical selected from the group consisting of an alkyl group having 1 to 6 carbon atoms and a (CH2)m —COQR3 group in which is an integer of between 1 and 5 and R3 represents an alkyl group having 1 to 6 carbon atoms;
• R2 represents an alkyl group having 1 to 6 carbon atoms;
• and
• n is an integer of between 1 and 5;
• said homopolymer having a molecular weight of 1,000 to 100,000,
• comprising the steps of:
• a) preparing a first solution of the polymer comprising the support material in a volatile organic solvent;
• b) preparing a second solution non-miscible with the solution obtained in step a), containing said substance to be dispersed;
• c) preparing a first emulsion by dispersing the second solution in the first solution, the solution of polymer forming a continuous phase;
• d) preparing a second emulsion either by dispersing, with agitation, the first emulsion obtained in step c) in a dispersing medium non-miscible with said first emulsion, or by pouring with agitation, into said first emulsion, a solution comprising a medium non-miscible with said first emulsion;
• and
• e) evaporating said organic solvent with agitation.

A method of preparing microspheres having an average diameter of between 1μm and 100μm, constituted of a continuous network of a support material, said network incorporating a dispersed aqueous phase;

• said support material containing at least 70% by weight of a homopolymer constituted of recurring units of the following general formula (I):
• in which:
• R1 represents a radical selected from the group consisting of an alkyl group having 1 to 6 carbon atoms and a (CH2)m —COOR3 group in which m is an integer of between 1 and 5 and R3 represents an alkyl group having 1 to 6 carbon atoms;
• R2 represents an alkyl group having 1 to 6 carbon atoms;
• and
• n is an integer of between 1 and 5;
• said homopolymer having a molecular weight of 1,000 to 100,000,
• comprising the steps of:
• a) preparing a first solution of the polymer mentioned above comprising the support material in a volatile organic solvent, containing a surfactant agent;
• b) preparing a second solution non-miscible with the solution obtained in step a), and a surfactant agent;
• c) preparing a first emulsion by dispersing the second solution in the first solution, the solution of polymer forming a continuous phase;
• d) preparing a second emulsion either by dispersing, with agitation, the first-emulsion obtained in step c) in a dispersing medium non-miscible with said first emulsion, said dispersing medium containing a stabilizing agent, or by pouring with agitation, into said first emulsion, a solution comprising a medium non-miscible with said first emulsion, said medium containing a stabilizing agent;
• and
• e) evaporating said organic solvent with agitation.

A method of preparing microspheres having an average diameter of between 1 μm and 100 μm, constituted of a continuous network of a support material, said network incorporating a dispersed aqueous phase;

• said support material containing at least 70% by weight of a homopolymer constituted of recurring units of the following general formula (I):
• in which:
• R1 represents a radical selected from the group consisting of an alkyl group having 1 to 6 carbon atoms and a (CH2)m —COOR3 group in which m is an integer of between 1 and 5 and R3 represents an alkyl group having 1 to 6 carbon atoms;
• R2 represents an alkyl group having 1 to 6 carbon atoms;
• and
• n is an integer of between 1 and 5;
• said homopolymer having a molecular weight of 1,000 to 100,000,
• comprising the steps of:
• a) preparing a first solution of the polymer comprising the support material in a volatile organic solvent, containing a surfactant agent;
• b) preparing a second solution non-miscible with the solution obtained in a), containing said substance to be dispersed, and a surfactant agent;
• c) preparing a first emulsion by dispersing the second solution in the first solution, the solution of polymer forming a continuous phase;
• d) preparing a second emulsion either by dispersing, with agitation, the first emulsion obtained in c) in a dispersing medium non-miscible with said first emulsion, said dispersing medium containing a stabilizing agent, or by pouring with agitation, into said first emulsion, a solution comprising a medium non-miscible with said first emulsion, said medium containing a stabilizing agent;
• and
• e) evaporating said organic solvent with agitation.