Abstract: Chemotherapeutic agents comprising an antigen binding dimer derived from an immunoglobulin covalently bound to a drug are disclosed. The dimer and drug are bound, while preserving both the antibody activity of the dimer and the pharmacological activity of the drug.

Abstract: The invention concerns orthoester and orthocarbonate polymers having a repeating mer comprising a hydrocarbon radical and a symmetrical dioxycarbon unit of the general formula: ##STR1## WHEREIN R.sub.1 is a multivalent hydrocarbon radical, R.sub.2 and R.sub.3 are hydrocarbon radicals with at least one of R.sub.2 or R.sub.3 bonded to the dioxycarbon through an oxygen linkage, and which polymers are synthesized by reacting a polyol with an orthoester or orthocarbonate. The polymers are useful for making articles of manufacture, including devices and coatings for delivering beneficial agents.

Abstract: Method for imparting compensatory vestibular-proprioceptive stimulation to a premature infant to prevent apnea in which the infant is placed on a waterbed and random oscillations of low amplitude and predetermined frequency are generated in the bed by an oscillator placed under the bed.

Abstract: A high speed process and apparatus are disclosed for forming outlet passageways of accurate, predetermined size in the walls of pills which dispense their contents by osmotically pumping said contents out said outlet passageways. The pills are moved in succession by an indexer past a passageway forming station where the pills are tracked seriatim at the velocity at which they are moving by an optical tracking system focused on the pill wall and into which a laser beam is directed. During the tracking the laser is fired and the laser beam is transmitted by the optical tracking system onto the wall of the moving pill, the laser power, laser beam dimensions and firing duration being such as to cause the laser beam to heat and pierce the pill wall, thereby forming said outlet passageway.

Abstract: Poly(orthoester carbonates) and poly(orthocarbonate carbonates) having a repeating linear carbonate unit and a recurring symmetrical dioxycarbon moiety with a plurality of organic groups pendant from the carbon atom thereof are disclosed. The polymers are represented by the structural formula: ##STR1## WHEREIN A IS 0 TO 1, B IS 2 TO 6 WHEN A IS 0, B IS 2 TO 5 WHEN A IS 1, AND N IS GREATER THAN 10.

Abstract: An osmotic device for delivering an active agent is disclosed. The device is comprised of a wall surrounding a compartment and has a passageway through the wall for releasing the agent. The wall is formed of a multiplicity of materials comprising a material permeable to an external fluid and substantially impermeable to agent and at least one additional material selected from a material that imparts stability to the wall, enhances the permeability of the wall to fluids, or aids in forming the wall. The compartment comprises an active agent that exhibits an osmotic pressure gradient against an external fluid, or the agent is mixed with an osmotically effective compound that exhibits an osmotic pressure gradient against the fluid.

Abstract: Poly(orthoester) co- and homopolymers and poly(orthocarbonate) co- and homopolymers comprising (1) a repeating dioxycarbon unit in the polymeric backbone having a plurality of organic groups pendant therefrom, and (2) a bridging moiety having at least one carbonyloxy group contained therein are disclosed. The polymers are represented by the formula: ##STR1## wherein R is a bridging moiety and is either R.sub.1 or R.sub.2 arranged in a random manner along the polymeric backbone to form a copolymer containing both R.sub.1 and R.sub.2 with R.sub.1 an aliphatic, an alicyclic or an aromatic group and R.sub.2 is a ##STR2## GROUP WITH R.sub.1 as defined and R.sub.3 an aliphatic, an alicyclic or aromatic group, or wherein R is a bridging moiety and is only R.sub.2 to form a homopolymer with R.sub.1, R.sub.2 and R.sub.3 as defined above, and a is 0 to 1, b is 2 to 6, and n and the sum of x and y are positive integers.

Abstract: This invention concerns polymeric orthoesters having a repeating mer comprising a hydrocarbon radical and an orthoester functionality of the general formula: ##STR1## wherein R.sub.1 is a monovalent radical, R.sub.2 is a hydrocarbon radical, a is 2 to 3, and n is at least 10. The polymers are useful for making articles of manufacture and as coatings for beneficial agents.

Abstract: This invention concerns pharmaceutically acceptable intramolecularly cross-linked, stromal-free hemoglobin. The intramolecularly cross-linked, stromal-free hemoglobin is useful as a blood substitute for carrying oxygen to tissues and vital organs, as a blood plasma expander, and for supplying oxygen to oxygen-requiring environments.

Abstract: Method and therapeutic system in the form of a bandage for providing chemotherapy transdermally by administering certain drugs to unbroken skin in an initial priming dose that quickly brings the systemic concentration of drug to a therapeutic level, followed by a substantially constant dosage that holds said level. The bandage is a four-layer laminate of, from the top: a protective backing; a drug reservoir lamina that is the source of the constant dosage; a microporous membrane that controls the constant dosage rate; and an adhesive layer that is the source of the priming dose and the means by which the bandage is attached to the skin.

Abstract: An osmotic system for delivering an agent is disclosed. The system comprises a wall surrounding a compartment and has a passageway for delivering agent from the compartment. The wall is formed of a laminae comprising a lamina consisting of a multiplicity of materials in laminar arrangement with a lamina consisting of a material or of a multiplicity of materials to provide a laminated wall that is permeable to agents and maintains its integrity during the delivery of agent. The compartment contains an agent that is soluble in an external fluid and exhibits an osmotic pressure gradient across the wall against the fluid, or the agent has limited solubility in the fluid and is mixed with an osmotically effective compound soluble in the fluid and exhibits an osmotic pressure gradient across the wall against the fluid.

Abstract: An ocular therapeutic system for releasing a drug to the eye at a controlled and continuous rate for a prolonged period of time is disclosed. The system is shaped, sized and adapted for insertion and retention in the eye. The system contains an ophthalmically acceptable drug and it is formed of a polymeric material permeable to the passage of drug by diffusion. The material is an ethylene-vinyl ester copolymer of the general formula: ##STR1## WHEREIN R is hydrogen, alkyl of 2 to 7 carbons, or aryl, m is (4 to 80)% by weight and n is (100 - m)% by weight.

Abstract: This invention concerns polymerized, cross-linked, stromal-free hemoglobin useful as a blood substitute for carrying oxygen to tissues and organs, as a blood plasma expander and for supplying oxygen to oxygen-requiring environments.

Abstract: An apparatus and method for winding an elastomeric fiber under no or low tension in which a spool of the fiber is placed between a pair of spaced rotating wheels thus causing the spool to rotate at a predetermined linear velocity, and the fiber is first passed from the spool around a take off pulley rotating faster than the spool, then around a substantial portion of the circumferences of a series of guide sheaves, each of which is rotating at the predetermined velocity, and then onto a wind up reel that is also rotating at the predetermined velocity. The speed of the rotating wheels is adjusted during the winding to compensate for the decrease in the spool's diameter as the fiber is unwound from it and for any inherent tension in the spooled fiber in order to keep the spool rotating at substantially the predetermined velocity.

Abstract: An infant waterbed for use in an incubator is disclosed that comprises a tray, a flexible mattress that sits in the tray and holds a fluid, such as water, that is capable of supporting an infant, a cover that fits over the top of the tray to separate the infant from the mattress, a frame that surrounds the cover and fits over the edge of the tray to hold the cover in place, and an oscillator that includes a bladder that sits under the mattress and means for inflating and deflating the bladder randomly at a predetermined frequency. Compensatory vestibular-proprioceptive stimulation is imparted to premature infants by placing them on the above described oscillating waterbed.

Abstract: An adjustable valvuloplasty ring that comprises a C-shaped frame that is sized and shaped to extend about the circumference of the left atrioventricular orifice along the base of the anterior cusp of the mitral valve; an expandable sleeve connected to the frame that together therewith forms a closed annulus, the sleeve being adapted to extend about the remainder of the circumference of the orifice; and a drawstring running through the sleeve by which the sleeve may be contracted to constrict and remodel the orifice and secured in place to maintain such constriction.

Abstract: An osmotic device for releasing a useful agent at different release rate patterns from the device in a selected environment is disclosed. The device is comprised of a wall surrounding and forming a compartment as a means for containing a useful agent and having a passageway for releasing the agent. The wall is comprised in at least a part of a material permeable to an external fluid and impermeable to the agent. A layer of a pattern rate controlling material that erodes in a selected environment for changing the release rate pattern of the device is carried on the semipermeable wall distant from the compartment. The agent is soluble in the fluid and exhibits an osmotic pressure gradient across the semipermeable wall against the fluid, or the agent has limited solubility and is admixed with an osmotically effective solute soluble in the fluid that exhibits an osmotic pressure gradient across the semipermeable wall against the fluid.

Abstract: An anatomically configured stent for a tanned, expanded natural tissue heart valve, a valve prosthesis including the stent, and a process for preparing the prosthesis are disclosed. The stent comprises a frame having three struts, two of which are biased radially inwardly and the third of which is also biased radially inwardly or generally parallel to the frame axis and a fabric cover covering at least the exterior of the frame, the cover having a bead along its perimeter that provides a site for attachment of the valve to the stent.

Abstract: An osmotic device for delivering an active agent is disclosed. The device is comprised of a wall surrounding a compartment and has a passageway through the wall for dispensing the agent. The wall is formed of a material permeable to an external fluid and substantially impermeable to agent and a gas generating means. The compartment is comprised of an active agent and a gas generating means that either exhibits an osmotic pressure gradient against the external fluid, or the means is mixed with an osmotically effective compound that exhibits an osmotic pressure gradient against the fluid. Agent is released by fluid being imbibed through the wall into the compartment at a rate controlled by the permeability of the wall and the osmotic pressure gradient across the wall, which fluid wets the means causing it to react and produce an effervescent solution containing agent that is dispensed under pressure through the passageway to the exterior of the device.

Abstract: An osmotic device for delivering an active agent is disclosed. The device is comprised of a wall surrounding in at least a part, a reservoir containing agent. The wall is formed of a material permeable to an external fluid and impermeable to agent. The reservoir is formed of a microporous material permeable to agent and fluid, and having at least one micropore that is a passageway for release of agent. The agent is soluble in the fluid and exhibits an osmotic pressure gradient against the fluid, or the agent has limited solubility in the fluid and is admixed with an osmotically effective compound soluble in fluid that exhibits an osmotic pressure gradient against fluid. In operation, agent is released by fluid permeating through the wall into the reservoir producing a solution of agent or a solution of compound containing agent, which solution in either instance is released through the micropore to the exterior of the device.