Colloidal suspension of submicronic particles as vectors for active principles and method for preparing same

a technology of submicronic particles and colloidal suspensions, which is applied in the field of colloidal suspensions of vector particles, can solve the problems that the composition gel microparticles do not meet the specifications, and achieve the effect of high bioavailability and easy and economical production

Inactive Publication Date: 2007-10-25
FLAMEL TECHNOLOGIES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0038] Another essential objective of the invention is to provide injectable medicinal suspensions. The specifications, which are required for such suspensions, are a low volume for injection and a low viscosity. It is important for the mass of colloidal particles per injection dose to be as low as possible, without limiting the quantity of active principle PA transported by these particles, so as not to damage the therapeutic efficacy.
[0048] Another objective of the present invention is to provide a medicament, such as the system for prolonged release of active principles, which is easy and economical to produce and which is, in addition, biocompatible and capable of providing a very high level of bioavailability of the PA.

Problems solved by technology

Under these conditions, it is obvious that the composite gel microparticles do not meet the specifications, and in particular not the specifications relating to injectability and to the capacity for combination and for release in relation to insulin.

Method used

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  • Colloidal suspension of submicronic particles as vectors for active principles and method for preparing same
  • Colloidal suspension of submicronic particles as vectors for active principles and method for preparing same
  • Colloidal suspension of submicronic particles as vectors for active principles and method for preparing same

Examples

Experimental program
Comparison scheme
Effect test

example 1

Production, in Aqueous Stable Colloidal Suspension and in Pulverulent Solid Form, of Vector Particles, from a Block Polyamino Acid, Poly(Leu / Glu) 40 / 80 Diblock

[0174] 112.4 g of NCA-GluOMe (0.60 mol) and 449 g of N-methyl-2-pyrrolidinone (NMP) are introduced, with stirring, into a 1 liter reactor thermostated at 20° C. After dissolution, 21.38 g of a 0.34 M solution of ammonia in 1,4-dioxane (1.25 mol % / NCA) are added. The polymerization is monitored by measuring the carbon dioxide emitted into a gas bell jar and verified by disappearance of vibration bands characteristic of the NCAs at 1860 and 1790 cm−1. After 30 min, a solution of 47.17 g of NCA Leucine (0.30 mol) in 631 g of NMP is introduced. After 10 min of reaction, the temperature is increased to 60° C. The polymerization is monitored as above and is complete after 2 hours. The temperature of the reaction mixture obtained is increased to 80° C. 31.5 g of aqueous concentrated hydrochloric acid (35%, 12 M) are added, with mech...

example 2

Combination of Insulin with the Nanoparticles of Poly(Leu / Glu) 40 / 80

[0177] The procedure Ma is used. The concentration of free insulin, assayed by HPLC chromatography is equal to 0.59 mg / ml and the combined insulin concentration equal to 1.51 mg / ml is deduced therefrom. The load capacity for a colloidal solution of 10 mg / ml reaches 1.51 mg / ml of insulin. Thus, the ratio of the mass of combined insulin to the bLE (Ta) mass is 15.1%.

example 3

Production, in Stable Colloidal Aqueous Suspension and in Pulverulent Solid Form, of Vector Particles from a Block PAA Poly(Leu / Glu) 25 / 70 Biblock

[0178] 146.4 g of NCA GluOMe are dissolved in 586 g of NMP to which 18.43 g of a 0.48 M solution of ammonia in methanol are added. When the polymerization of the NCA GluOMe is complete, a solution of 43.9 g of NCA Leu in 708 g of NMP is introduced and the polymerization of the NCAs Leu is continued until disappearance of the monomers is obtained. The medium is then heated to 80° C. and 129.4 g of 35% HCl are added dropwise thereto over 30 min to 1 hour. A 600 mBar vacuum is applied for 6 hours, and then an additional 129.4 g of 35% HCl are added as a mixture with 517.5 g of water. A 250 mBar vacuum is then applied for 18 hours. After this step, the temperature is reduced to 50° C., 1 liter of water is introduced, followed by 280 ml of 35% NaOH in order to bring the pH to 7.4. The suspension is then filtered (5 μm), dialyzed (cut-off 1 000...

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Abstract

A suspension of vector particles (PV) based on polyamino acids and have a mean hydrodynamic diameter between 30 and 120 nm, and an insulin load factor of from 5 to 25% of associated insulin volume relative to the polyamino acid volume forming the vector particles. The polyamino acids are double-block polymers containing hydrophilic and hydrophobic monomers. The suspension may be prepared by copolymerizing N-carboxy anhydrides of hydrophobic monomers and precursors of hydrophilic monomers, in the presence of N-methyl pyrrolidone and methanol. The copolymer is optionally neutralized, subjected to dialysis, concentrated and water is eliminated to produce a solid powder, which can be suspended in a liquid to produce the colloidal suspension. Active principles such as insulin or vaccines are associated with the carrier particles to prepare special pharmaceutical products.

Description

TECHNICAL FIELD [0001] The field of the present invention is that of Vector Particles (PV), which are useful for the administration of active principles (PA). The latter are preferably medicaments or nutrients for administration to an animal or human organism by the oral, nasal, vaginal, ocular, subcutaneous, intravenous, intramuscular, intradermal, intraperitoneal, intracerebral or parenteral route, or the like. However, this may also involve cosmetic products or plant-production products, such as herbicides, pesticides, insecticides or fungicides, or the like. In terms of chemical nature, the PAs most particularly, but without limitation, involved in the invention are, for example, proteins, glycoproteins, peptides, polysaccharides, lipopolysaccharides, oligonucleotides, polynuclides and organic molecules. [0002] The present invention relates, more precisely, to colloidal suspensions of Vector Particles, advantageously of the submicronic type, based on polyamino acids (PAA). The p...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K9/14A61K31/7042A61K31/7088A61K31/715A61K31/727A61K39/00A61K8/02C12N15/09A61K8/04A61K8/30A61K8/64A61K8/90A61K9/107A61K9/16A61K9/51A61K9/52A61K38/28A61K47/42A61P3/10A61Q19/00B01J13/00
CPCA61K8/044A61K8/90A61K9/5138B82Y5/00A61Q19/00B01J13/0021A61K2800/413A61P3/10A61K9/16
Inventor TOURAUD, FRANCKBRYSON, NATHAN
Owner FLAMEL TECHNOLOGIES
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