News Column

Patent Issued for Pharmaceutical Compositions of Dextran Polymer Derivatives and a Carrier Material

September 8, 2014



By a News Reporter-Staff News Editor at Pharma Business Week -- According to news reporting originating from Alexandria, Virginia, by NewsRx journalists, a patent by the inventors Friesen, Dwayne T. (Bend, OR); Vodak, David T. (Bend, OR), filed on August 31, 2011, was published online on August 26, 2014 (see also Bend Research, Inc.).

The assignee for this patent, patent number 8815294, is Bend Research, Inc. (Bend, OR).

Reporters obtained the following quote from the background information supplied by the inventors: "Pharmaceutically active agents are generally formulated as solid or liquid dosage forms for administration. Such dosage forms generally comprise the active agent combined with excipients to form materials that may be conveniently and reliably administered to a patient in need of such therapy, and following administration, the active agent is absorbed and distributed in the patient in a way that leads to good efficacy and safety.

"It is known that poorly water-soluble drugs may be formulated as nanoparticles. Nanoparticles are of interest for a variety of reasons, such as to improve the bioavailability of poorly water-soluble drugs, to provide targeted drug delivery to specific areas of the body, to reduce side effects, or to reduce variability in vivo.

"A variety of approaches have been taken to formulate drugs as nanoparticles. One approach is to decrease the size of crystalline drug by grinding or milling the drug in the presence of a surface modifier. Another approach to forming nanoparticles is to precipitate the drug in the presence of a film forming material such as a polymer.

"There remain a number of problems associated with the use of nanoparticles to deliver pharmaceutical compounds to the body. The nanoparticles must be stabilized so that they do not aggregate into larger particles in aqueous suspensions. Often surface modifiers such as surfactants are used to stabilize the nanoparticles, but such materials can have adverse physiological effects when administered in vivo. In addition, without a surface modifier present, the surface of the nanoparticles is unprotected, leading to a decrease in performance and stability.

"In addition, it is often desirable to formulate nanoparticles as a dry material to improve patient compliance and facilitate incorporating the nanoparticles into a suitable dosage form. However, when liquids are removed from suspensions of nanoparticles, the nanoparticles often agglomerate or aggregate. When the resulting dry material is then administered to an aqueous solution (either in vitro or in vivo), large particles are formed, corresponding to the agglomerated or aggregated nanoparticles. These aggregates or agglomerated particles reduce the performance of the formulation.

"Accordingly, there is a continuing need for nanoparticles that are stable, in the sense of not aggregating into larger particles, and that improve the bioavailability of active agents."

In addition to obtaining background information on this patent, NewsRx editors also obtained the inventors' summary information for this patent: "A pharmaceutical composition comprises (a) nanoparticles comprising an active agent and a dextran polymer derivative, and (b) a carrier material. The nanoparticles have an average size of less than 1000 nm. The carrier material constitutes from 5 wt % to 99 wt % of the combined mass of (1) said nanoparticles and (2) said carrier material. The dextran polymer derivative is selected from dextran acetate, dextran propionate, dextran succinate, dextran acetate propionate, dextran acetate succinate, dextran propionate succinate, dextran acetate propionate succinate, and mixtures thereof.

"In one embodiment, the carrier material is selected from synthetic polymers, polysaccharides, derivatized polysaccharides, sugars, sugar alcohols, organic acids, salts of organic acids, inorganic salts, proteins, amino acids, phospholipids, and pharmaceutically acceptable forms, derivatives, and mixtures thereof.

"In one embodiment, the carrier material is selected from polyvinyl pyrrolidone (PVP), polyethyleneoxide (PEO), poly(vinyl pyrrolidone-co-vinyl acetate), polymethacrylates, polyoxyethylene alkyl ethers, polyoxyethylene castor oils, polycaprolactam, polylactic acid, polyglycolic acid, poly(lactic-glycolic)acid, cellulose, pullulan, dextran, maltodextrin, hyaluronic acid, polysialic acid, chondroitin sulfate, heparin, fucoidan, pentosan polysulfate, spirulan, hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), carboxymethyl ethylcellulose (CMEC), hydroxypropyl methylcellulose acetate succinate (HPMCAS), ethyl cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, trehalose, glucose, sucrose, raffinose, lactose, mannitol, erythritol, xylitol, polydextrose, oleic acid, citric acid, tartaric acid, edetic acid, malic acid, sodium citrate, sodium bicarbonate, albumin, gelatin, acacia, casein, caseinate, glycine, leucine, serine, alanine, isoleucine, tri-leucine, lecithin, phosphatidylcholine, and pharmaceutically acceptable forms, derivatives, and mixtures thereof.

"In another embodiment, the carrier material is selected from lactose, mannitol, trehalose, sucrose, citric acid, sodium citrate, leucine, glycine, dextran, and pharmaceutically acceptable forms, derivatives, and mixtures thereof.

"In one embodiment, the nanoparticles comprise from 0.01 to 99 wt % of an active agent and from 1 to 99.99 wt % of a dextran polymer derivative. In another embodiment, the active agent and the dextran polymer derivative constitute at least 75 wt % of the nanoparticles. In still another embodiment, the active agent and the dextran polymer derivative constitute at least 90 wt % of the nanoparticles. In yet another embodiment, the nanoparticles consist essentially of the active agent and the dextran polymer derivative.

"In one embodiment, the dextran polymer derivative is selected from dextran succinate, dextran acetate succinate, dextran propionate succinate, dextran acetate propionate succinate, and mixtures thereof. In another embodiment, the dextran polymer derivative is selected from dextran acetate succinate, dextran propionate succinate, dextran acetate propionate succinate, and mixtures thereof.

"In one embodiment, the dextran polymer derivative has a degree of substitution (DS) for acetate substituents of 0 to 2.8, a DS for propionate substituents of 0 to 2.8, and a DS for succinate substituents of 0 to 2.8. In another embodiment, the dextran polymer derivative has a degree of substitution for succinate of at least 0.05.

"In one embodiment, the dextran polymer derivative has a molecular weight ranging from 3000 daltons to 100,000 daltons. In another embodiment, the dextran polymer derivative has a molecular weight ranging from 3000 daltons to 70,000 daltons.

"In one embodiment, the composition is formulated for inhalation, and the dextran polymer derivative is at least one of aqueous soluble and enteric.

"In one embodiment, the dextran polymer derivative is dextran acetate. In another embodiment, the dextran polymer derivative is dextran propionate. In another embodiment, the dextran polymer derivative is dextran succinate. In yet another embodiment, the dextran polymer derivative is dextran acetate propionate. In another embodiment, the dextran polymer derivative is dextran acetate succinate. In another embodiment, the dextran polymer derivative is dextran propionate succinate. In still another embodiment, the dextran polymer derivative is dextran acetate propionate succinate.

"In one embodiment, the composition is administered to an animal via a mode selected from oral, buccal, mucosal, sublingual, intravenous, intra-arterial, intramuscular, subcutaneous, intraperitoneal, intraarticular, infusion, intrathecal, intraurethral, topical, subdermal, transdermal, intranasal, inhalation, pulmonary tract, intratracheal, intraocular, ocular, intraaural, vaginal, and rectal.

"In one embodiment, the composition comprises a plurality of particles having a mass median aerodynamic diameter of 0.5 to 100 .mu.m for inhalation. In another embodiment, the composition comprises a plurality of particles having a mass median aerodynamic diameter of 10 to 100 .mu.m for inhalation, wherein a weight fraction of particles having a mass median aerodynamic diameter of less than 10 .mu.m is less than 0.1. In yet another embodiment, the composition comprises a plurality of particles having a mass median aerodynamic diameter of 0.5 to 10 .mu.m for delivering an active agent to lower airways, wherein a weight fraction of particles having a mass median aerodynamic diameter of greater than 10 .mu.m is less than 0.1.

"Disclosed embodiments of the pharmaceutical composition provide one or more of the following advantages. Because the pharmaceutical composition comprises (a) nanoparticles comprising an active agent and a dextran polymer derivative, and (b) a carrier material, when added to an aqueous solution the composition rapidly forms a nanoparticle suspension.

"The dextran polymer derivatives have a combination of substituent degrees of substitution tailored to provide utility for nanoparticle compositions.

"When used to form combinations of active agents, such polymers provide enhanced concentrations of dissolved active agent in a use environment. When used in combination with active agents that are prone to rapid crystallization from supersaturated aqueous solutions, such polymers are particularly effective at sustaining high concentrations of the active agent and thereby enhancing absorption of active agent in vivo. The compositions also provide a more stable composition.

"The foregoing and other objectives, features, and advantages of the invention will be more readily understood upon consideration of the following detailed description of the invention."

For more information, see this patent: Friesen, Dwayne T.; Vodak, David T.. Pharmaceutical Compositions of Dextran Polymer Derivatives and a Carrier Material. U.S. Patent Number 8815294, filed August 31, 2011, and published online on August 26, 2014. Patent URL: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=8815294.PN.&OS=PN/8815294RS=PN/8815294

Keywords for this news article include: Acyclic Acids, Bend Research, Bend Research Inc., Branched-Chain Amino Acids, Dicarboxylic Acids, Emerging Technologies, Essential Amino Acids, Leucine, Nanoparticle, Nanotechnology, Propionates, Succinates, Succinic Acids.

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Source: Pharma Business Week


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