Microparticulate material and method of making such material

• US 3,959,457 A
• Filed: 02/08/1973
• Issued: 05/25/1976
• Est. Priority Date: 06/05/1970
• Status: Expired due to Term

• Current Assignee: Temple University
• Original Assignee: Temple University
• Inventors: Speaker, Tully J., Lesko, Lawrence J.
• Primary Examiner(s): Lovering, Richard D.
• Application Number:
  US05/330,476
• Time in Patent Office: 1,202 Days
• Field of Search: 252/316, 117/100 A, 424/19, 424/22, 424/34, 424/35, 264/4, 106/208, 106/186, 106/205, 106/197 C, 260/209 R
• US Class Current: 424/1.25
• CPC Class Codes: A61K 9/5036 Polysaccharides, e.g. gums, alginate; Cyclodextrin
• CPC Class Codes: A61K 9/5089 Processes
• CPC Class Codes: Y10T 428/2989 Microcapsule with solid core [includes liposome]

Abstract

In a finely dispersed emulsion of a water immiscible solution of an organic polyfunctional Lewis base and an aqueous solution of a partially hydrophilic, partially lipophilic polyfunctional Lewis acid, a reaction occurs at the phase interface to produce a novel microparticulate material comprised of the reaction product of the Lewis acid and the Lewis base. The maximum particle size dimensions of the microparticulate material depends on the degree of dispersion in the emulsified reaction mixture and may be as low as 2 microns or smaller.

Claims

1. Microparticulate material, consisting essentially of the ionically bonded reaction product of an emulsion of

a. a water immiscible solution of piperazine, and

b. an aqueous solution of a partially hydrophilic, partially lipophilic, polyfunctional Lewis acid selected from the group consisting of acacia gum, arabic acid, carboxymethyl-cellulose, ghatti gum, guar gum, methylcellulose, oxidized cellulose, pectin, tragacanth, polyethylene glycol and agar, and wherein said water immiscible solution comprises, as the solvent thereof, a polar solvent having a dielectric constant of no less than 4 Debye units.

2. Microparticulate material, consisting essentially of the ionically bonded reaction product of an emulsion of

a. a water immiscible solution of a Lewis base, and

b. an aqueous solution of acacia, wherein said Lewis base is selected from the group consisting of hexylamine, isopentylamine, n-methylpiperidine, piperidine, dimethylenediamine, hexanediamine, piperazine, triethylene diamine, ethylenediamine, hexamethylrosanilium cation, rosanilium cation, tetramethylrosanilium cation, melamine, tetraethylpentamine and triethyltetramine, and wherein said water immiscible solution comprises, as the solvent thereof, a polar solvent having a dielectric constant of no less than 4 Debye units.

3. Microparticulate material, as recited in claim 2, wherein said solvent is chloroform and said base is piperazine.

4. Microparticulate material, consisting essentially of the ionically bonded reaction product of an emulsion of

a. a water immiscible solution of a Lewis base, and

b. an aqueous solution of a partially hydrophilic, partially lipophilic, polyfunctional Lewis acid, wherein said Lewis base is selected from the group consisting of hexylamine, isopentylamine, n-methylpiperidine, piperidine, dimethylethylenediamine, hexanediamine, piperazine, triethylene diamine, ethylenediamine, hexamethylrosanilium cation, rosanilium cation, tetramethylrosanilium cation, melamine, tetraethylpentamine and triethyltetramine, and said Lewis acid is selected from the group consisting of acacia gum, arabic acid, carboxymethylcellulose, ghatti gum, guar gum, methylcellulose, oxidized cellulose, pectin, tragacanth, polyethylene glycol and agar, wherein said water immiscible solution comprises, as the solvent thereof, a polar solvent having a dielectric constant of no less than 4 Debye units, and wherein said microparticulate material further includes, entrapped in said reaction product, a material essentially non-reactive with the reactants and reaction product therein and which is diffusible through said reaction product.

5. Microparticulate material, as recited in claim 4, wherein said entrapped material has pharmaceutical activity.

6. A method of producing a microparticulate material, said method comprising

a. adding to an aqueous solution of a partially hydrophilic, partially lipophilic, polyfunctional Lewis acid, a water immiscible solution of a Lewis base,

b. maintaining said solutions in an agitated condition during and after the mixing thereof,

c. separating and washing the water immiscible phase, and

d. removing any remaining solvent in said water immiscible phase,

wherein said polyfunctional Lewis acid is selected from the group consisting of acacia gum, arabic acid, carboxmethylcellulose, ghatti gum, guar gum, methylcellulose, oxidized cellulose, pectin, tragacanth, polyethylene glycol and agar, and said polyfunctional Lewis base is selected from the group consisting of hexylamine, isopentylamine, N-methylpiperidine, piperidine, dimethylethylenediamine, hexanediamine, piperazine, triethylene diamine, ethylenediamine hexamethylrosanilinium cation, rosanilinium cation, tetramethylrosanilinium cation, melamine, tetraethylpentamine and triethyltetramine, and said water immiscible solution comprises, as the solvent thereof, a polar solvent having a dielectric constant of no less than 4 Debye units.

7. Method, as recited in claim 6, wherein said solvent is selected from the group consisting of bromoform, chloroform, dichloromethane, dichloroethane, diethyl ether, diisopropyl ether, methyl ethyl ketone and nitrobenzene.

8. Method, as recited in claim 6, wherein said solvent is chloroform.

9. Method, as recited in claim 6, wherein said polyfunctional Lewis base is piperazine.

10. Method, as recited in claim 6, wherein said polyfunctional Lewis acid is acacia.