MannKind 2006 Annual Report
May 29, 2018 18:38:58 GMT -5
centralcoastinvestor, peppy, and 3 more like this
Post by mango on May 29, 2018 18:38:58 GMT -5
This is a really cool MannKind artifact, enjoy! ✌️
FORMULATION TECHNOLOGY ■
Technosphere® Insulin’s rapid action may be related to unique characteristics of both our carrier molecule and the insulin in our formulation.
Our Technosphere® formulation technology is centered on a class of pH-sensitive organic molecules that self-assemble into small particles under mildly acidic conditions. Certain drugs, such as insulin, can be loaded onto these particles by combining a mildly acidic solution of the drug with a suspension of Technosphere® material, which is dried to a powder. This powder is then filled into plastic cartridges and packaged.
To administer Technosphere® Insulin, a patient loads a cartridge into our palm-sized inhaler. By inhaling through the inhaler, air is pulled through the cartridge, which aerosolizes the powder and pulls the particles into the air current and out through the mouthpiece. The particles are small and have aerodynamic properties that enable them to travel deep into the lungs.
When the particles contact the moist lung surface with its neutral pH, the Technosphere® particles dissolve immediately. This releases the insulin molecules, which then diffuse across a
thin layer of cells into the bloodstream. Studies indicate that the insulin absorption is a passive process that occurs without disruption of either the cell membranes or the tight junctions between cells.
INSULIN MONOMERS ■
When the Technosphere® particles dissolve, the insulin that is released is in a form that can readily be used by the body.
In most pharmaceutical dosage forms, regular human insulin exists as a hexamer, a complex of six associated insulin molecules. In order to exert a pharmacological effect, the hexamer must first dissociate into three dimers complexes of two insulin molecules — which then further dissociate into individual insulin molecules, or monomers. Only these monomers exert a physiological effect. Rapid-acting insulin analogs are designed to be fragile hexamers that dissociate more quickly than regular insulin, thereby reducing the time required to achieve an effect, but this is still far slower than insulin that is released from a healthy pancreas.
The insulin released from Technosphere® particles is already largely in monomeric form. During the manufacture of Technosphere® Insulin, we cause hexameric insulin to dissociate into insulin monomers before being loaded onto Technosphere® particles.
These properties may explain why the Technosphere® Insulin System produces such a rapid elevation in insulin levels following inhalation. This time-action profile approximates the insulin profile normally seen in healthy individuals immediately following the beginning of a meal, but which is absent in patients with diabetes.
MannKind 2006 Annual Report
FORMULATION TECHNOLOGY ■
Technosphere® Insulin’s rapid action may be related to unique characteristics of both our carrier molecule and the insulin in our formulation.
Our Technosphere® formulation technology is centered on a class of pH-sensitive organic molecules that self-assemble into small particles under mildly acidic conditions. Certain drugs, such as insulin, can be loaded onto these particles by combining a mildly acidic solution of the drug with a suspension of Technosphere® material, which is dried to a powder. This powder is then filled into plastic cartridges and packaged.
To administer Technosphere® Insulin, a patient loads a cartridge into our palm-sized inhaler. By inhaling through the inhaler, air is pulled through the cartridge, which aerosolizes the powder and pulls the particles into the air current and out through the mouthpiece. The particles are small and have aerodynamic properties that enable them to travel deep into the lungs.
When the particles contact the moist lung surface with its neutral pH, the Technosphere® particles dissolve immediately. This releases the insulin molecules, which then diffuse across a
thin layer of cells into the bloodstream. Studies indicate that the insulin absorption is a passive process that occurs without disruption of either the cell membranes or the tight junctions between cells.
INSULIN MONOMERS ■
When the Technosphere® particles dissolve, the insulin that is released is in a form that can readily be used by the body.
In most pharmaceutical dosage forms, regular human insulin exists as a hexamer, a complex of six associated insulin molecules. In order to exert a pharmacological effect, the hexamer must first dissociate into three dimers complexes of two insulin molecules — which then further dissociate into individual insulin molecules, or monomers. Only these monomers exert a physiological effect. Rapid-acting insulin analogs are designed to be fragile hexamers that dissociate more quickly than regular insulin, thereby reducing the time required to achieve an effect, but this is still far slower than insulin that is released from a healthy pancreas.
The insulin released from Technosphere® particles is already largely in monomeric form. During the manufacture of Technosphere® Insulin, we cause hexameric insulin to dissociate into insulin monomers before being loaded onto Technosphere® particles.
These properties may explain why the Technosphere® Insulin System produces such a rapid elevation in insulin levels following inhalation. This time-action profile approximates the insulin profile normally seen in healthy individuals immediately following the beginning of a meal, but which is absent in patients with diabetes.
MannKind 2006 Annual Report
