Other

Akagera Medicines, Inc.

Zoneone Pharma, Inc.

Ipsen Biopharm Limited

Celator Pharmaceuticals, Inc.

Charles Noble

Mark Eamon Hayes

Dmitri B Kirpotin

Daryl C Drummond

Francis C Szoka, Jr

Alexander Koshkaryev

Suresh K Tipparaju

Kevin Kesper

Antoine M Awad

Douglas J Moore

Andrew J O'Brien

Compositions and methods for the treatment of tuberculosis, as well as other mycobacterial and gram positive bacterial infections are disclosed. These compositions contain a highly potent and selective oxazolidinone encapsulated with high efficiency to maximize dosing potential of low toxicity drugs, and are stable in the presence of plasma. The compositions are long circulating and retain their encapsulated drug while in the circulation following intravenous dosing to allow for efficient accumulation at the site of the bacterial or mycobacterial infection. The high doses that can be achieved when combined with the long circulating properties and highly stable retention of the drug allow for a reduced frequency of administration when compared to daily or twice daily administrations of other drugs typically utilized to treat these infections.

Oxazolidinone compounds, liposome compositions comprising oxazolidinone compounds and method of use thereof

The present invention provides liposome compositions containing sparingly soluble drugs that are used to treat life-threatening diseases. A preferred method of encapsulating a drug inside a liposome is by remote or active loading. Remote loading of a drug into liposomes containing a transmembrane electrochemical gradient is initiated by co-mixing a liposome suspension with a solution of drug, whereby the neutral form of the compound freely enters the liposome and becomes electrostatically charged thereby preventing the reverse transfer out of the liposome. There is a continuous build-up of compound within the liposome interior until the electrochemical gradient is dissipated or all the drug is encapsulated in the liposome. However, this process as described in the literature has been limited to drugs that are freely soluble in aqueous solution or solubilized as a water-soluble complex. This invention describes compositions and methods for remote loading drugs with low water solubility (<2 mg/mL). In the preferred embodiment the drug in the solubilizing agent is mixed with the liposomes in aqueous suspension so that the concentration of solubilizing agent is lowered to below its capacity to completely solubilize the drug. This results in the drug precipitating but remote loading is capability retained. The process is scalable and the resulting drug-loaded liposomes are characterized by a high drug-to-lipid ratios and predictable drug retention when the liposome encapsulated drug is administered in patients.

Remote loading of sparingly water-soluble drugs into lipid vesicles

Irinotecan phospholipid liposomes with improved storage stability are provided, with related methods of treatment and manufacture. The irinotecan liposomes can have reduced formation of lyso-phosphatidylcholine (lyso-PC) during storage, and prior to administration to a patient.

Stabilizing camptothecin pharmaceutical compositions

The present invention provides liposome compositions containing sparingly soluble drugs that are used to treat life-threatening diseases. A preferred method of encapsulating a drug inside a liposome is by remote or active loading. Remote loading of a drug into liposomes containing a transmembrane electrochemical gradient is initiated by co-mixing a liposome suspension with a solution of drug, whereby the neutral form of the compound freely enters the liposome and becomes electrostatically charged thereby preventing the reverse transfer out of the liposome. There is a continuous build-up of compound within the liposome interior until the electrochemical gradient is dissipated or all the drug is encapsulated in the liposome. However, this process as described in the literature has been limited to drugs that are freely soluble in aqueous solution or solubilized as a water-soluble complex. This invention describes compositions and methods for remote loading drugs with low water solubility (&#x3c;2 mg/mL). In the preferred embodiment the drug in the solubilizing agent is mixed with the liposomes in aqueous suspension so that the concentration of solubilizing agent is lowered to below its capacity to completely solubilize the drug. This results in the drug precipitating but remote loading is capability retained. The process is scalable and the resulting drug-loaded liposomes are characterized by a high drug-to-lipid ratios and predictable drug retention when the liposome encapsulated drug is administered in patients.

The present invention provides liposome compositions containing sparingly soluble drugs that are used to treat life-threatening diseases. A preferred method of encapsulating a drug inside a liposome is by remote or active loading. Remote loading of a drug into liposomes containing a transmembrane electrochemical gradient is initiated by co-mixing a liposome suspension with a solution of drug, whereby the neutral form of the compound freely enters the liposome and becomes electrostatically charged thereby preventing the reverse transfer out of the liposome. There is a continuous build-up of compound within the liposome interior until the electrochemical gradient is dissipated or all the drug is encapsulated in the liposome. However, this process as described in the literature has been limited to drugs that are freely soluble in aqueous solution or solubilized as a water-soluble complex. This invention describes compositions and methods for remote loading drugs with low water solubility (&#x3c;2 mg/mL). In the preferred embodiment the drug in the solubilizing agent is mixed with the liposomes in aqueous suspension so that the concentration of solubilizing agent is lowered to below its capacity to completely solubilize the drug. This results in the drug precipitating but remote loading capability is retained. The process is scalable and, in liposomes in which the lipid composition and remote loading agent are optimized, the resulting drug-loaded liposomes are characterized by a high drug-to-lipid ratios and prolonged drug retention when the liposome encapsulated drug is administered to a subject.

Remote loading of sparingly water-soluble drugs into liposomes

The present invention provides liposome compositions containing sparingly soluble drugs that are used to treat life-threatening diseases. A preferred method of encapsulating a drug inside a liposome is by remote or active loading. However, this process as described in the literature has been limited to drugs that are freely soluble in aqueous solution or solubilized as a water-soluble complex. This invention describes compositions and methods for remote loading drugs with low water solubility (&#x3c;2 mg/mL). In the preferred embodiment the drug in the solubilizing agent is mixed with the liposomes in aqueous suspension so that the concentration of solubilizing agent is lowered to below its capacity to completely solubilize the drug. This results in the drug precipitating but remote loading is capability retained. The process is scalable and the resulting drug-loaded liposomes are characterized by a high drug-to-lipid ratios and predictable drug retention when the liposome encapsulated drug is administered in patients.

A method and apparatus for centrifugal casting of metal articles uses a rotating mold body that can be pivoted from a vertical orientation to a horizontal orientation during the centrifugal casting of the metal article. The resulting metal article has a closed end and an open end defining a hollow cavity. The mold body has a closed end that is oriented in a vertical position with the longitudinal axis extending vertically. While the mold body is rotated, an amount of molten metal is introduced into the mold body so that the molten metal is distributed along the closed end of the mold body. In one embodiment, the bottom end of the mold body has a frustoconical shaped surface defining the mold cavity. The mold body is then pivoted to a horizontal position while continuously rotating to distribute and cast the metal against the inner surface of the mold body. In one embodiment, the mold body has a refractory lining of a compacted refractory material. The refractory material is introduced into the rotating mold and a blade is contacted with the layer of the refractory material formed on the inner surface while the mold is rotated in a first direction to compact and densify the layer of particles with a flat end of the blade. The rotation of the mold body is then reversed and the sharp edge of the blade is contacted with the compacted layer to shape and contour the mold lining.

Method and apparatus for centrifugal casting of metal

A method and apparatus for use in centrifugal casting of metal articles forms a compacted lining of a particulate refractory material on an inner surface of the mold. An amount of a dry binderless particulate refractory material is dispensed on the inner surface of a rotating mold body to form a centrifugally densified layer. A plowing tool is brought into contact with a layer of refractory material while continuously rotating the mold body to plow and compact the layer of particles. The tool is oriented at an angle with respect to the direction of travel of the layer of particles to penetrate the layer and compact the particles toward the inner surface of the mold body. The combination of the centrifugal force and the mechanical compaction of the particles results in a dense, air impervious, compacted mold lining having interlocked particles and voids between the particles that are not interconnected with an adjacent void. The mold is formed with at least one air inlet and at least one air outlet communicating with an inner surface of the mold. A porous lining is formed on the inner surface of the mold in communication with the air inlet and the air outlet. Rotation of the mold draws air through the inlet and the porous lining and out through the outlet to cool the lining during casting.

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San Francisco, CA, United States of America

Charles Noble