Method and device for fast dissolution of solid protein composition

Patent metadata

Field	Value
Publication number	US-11634473-B2
Application number	US-202016814088-A
Country	US
Kind code	B2
Filing date	Mar 10, 2020
Priority date	Dec 29, 2011
Publication date	Apr 25, 2023
Grant date	Apr 25, 2023

Abstract

Provided are methods and devices for dissolving solid protein compositions, such as solid compositions comprising fibrinogen, in an aqueous solvent. The methods comprise use of a closed container containing a volume of solid fibrinogen composition and a head space wherein the pressure within the headspace is sub-atmospheric. Aqueous solvent is introduced into the container while maintain the sub-atmospheric pressure, and subsequent to addition of the solvent, the size of the headspace is decreased to bring the pressure to atmospheric pressure. The devices are suitable for use in the disclosed method.

First claim

The invention claimed is:

1. A device suitable for dissolving a solid composition in an aqueous solvent, the device comprising:
a first closed container holding a first solid composition comprising low-density fibrinogen in the form of a porous sponge, the first closed container including a first closed container inlet having a closed state and an open state, wherein in the closed state the first closed container inlet is sealed to the passage of fluid and in the open state the first closed container inlet provides a path for fluid communication into the first closed container;
a first movable seal element arranged within the first closed container, for sealing the first closed container and configured to maintain sealing of the first closed container while moving therein between at least a first and a second position within the first closed container, to decrease the internal volume of the first closed container; the first movable seal element is configured to be releasably held in a first position within the first closed container;
a first controller for controlling changing of the first closed container inlet between a closed state and an open state,
a first reservoir suitable for holding a first aqueous solvent, the first reservoir comprising a first reservoir outlet adapted to be in fluid communication with the first closed container inlet; and
a second moveable seal element arranged within the first reservoir configured to maintain sealing of the first reservoir,
wherein: (i) when the first closed container inlet is in a closed state while the first movable seal element is in the second position, and subsequently the first movable seal element is moved to the first position and is kept held, a headspace having a sub-atmospheric pressure is formed, or
(ii) the device is provided with the closed container further containing a headspace with a sub-atmospheric pressure; a closed container inlet; and the first movable seal element being held in the first position;
wherein the first movable seal element is configured to be fixed in the first position while the aqueous solvent is allowed to flow into the interior volume of the closed container, thereby maintaining the headspace at a sub-atmospheric pressure;
and wherein the first closed container and the first reservoir are configured to allow agitation by repeated transfer of the aqueous solvent between the first reservoir and the first closed container;
the device being configured such that: when the container inlet is in the open state, the aqueous solvent is allowed to flow into the container; the container inlet is configured to be in the closed state after the aqueous solvent has flowed within the container; and when the container inlet is in the closed state, the first movable seal element is further configured to be released and to move from the first to the second position within the first closed container by a difference between atmospheric pressure outside the closed container and the sub-atmospheric pressure in the headspace, thereby decreasing the internal volume of the first closed container, such that the internal pressure within the first closed container is increased without allowing entry of gas into the container.

2. The device according to claim 1 , further comprising a controller actuator which when actuated, causes the first controller to move from the closed state to the open state.

3. The device according to claim 1 , wherein the first closed container comprises a first syringe barrel having a front end and a back end, wherein the front end comprises the first closed container inlet, and wherein the first moveable seal element comprises a first piston arranged within the first syringe barrel slidingly displaceable from the back end towards the front end of the first syringe barrel and connected to a first piston rod.

4. The device according to claim 3 , wherein the first piston is attached to a piston rod having at least one recess.

5. The device according to claim 1 , wherein the first reservoir comprises a second syringe barrel having a front end and a back end, wherein the front end comprises the first reservoir outlet, and the second moveable seal element comprises a second piston arranged within the second syringe barrel slidingly displaceable from the back end towards the front end of the second syringe barrel and connected to a second piston rod.

6. The device according to claim 1 , further comprising:
a second closed container suitable for holding a second solid composition, the second closed container including a second closed container inlet having a closed state and an open state, wherein in the closed state the second closed container is sealed to the passage of fluid and in the open state the second closed container inlet provides a path for fluid communication into the second closed container;
a third movable seal element arranged within the second closed container, for sealing the second closed container and configured to maintain sealing of the second closed container while moving therein between at least a first and a second position within the second closed container, to decrease the internal volume of the second closed container; and
a second controller for controlling changing of the second closed container inlet between a closed state and an open state,
wherein the device is provided with the second closed container further containing a headspace with a sub-atmospheric pressure; a closed container inlet; and the third movable seal element is kept hold in the first position; or when the second closed container inlet is in a closed state while the third movable seal element is in the second position, and subsequently the third movable seal element is moved to the first position and the third movable seal element is kept hold, a headspace having a sub-atmospheric pressure is formed.

7. The device according to claim 6 , wherein the second solid composition comprises solid thrombin.

8. The device according to claim 5 or 6 , further comprising a second reservoir suitable for holding a second aqueous solvent and a fourth moveable seal element arranged within the second reservoir configured to maintain sealing of the second reservoir, the second reservoir comprising a second fluid outlet adapted to be in fluid communication with the second container inlet.

9. The device according to claim 8 , wherein:
the first closed container is a first syringe barrel having a front end and a back end, wherein the front end of the first syringe barrel comprises the first closed container inlet and wherein the first moveable seal element of the first closed container comprises a first piston arranged within the first syringe barrel slidingly displaceable from the back end towards the front end of the first syringe barrel;
wherein the first reservoir comprises a second syringe barrel having a front end and a back end, wherein the front end of the second syringe barrel comprises the first reservoir outlet and wherein the second moveable seal element comprises a second piston arranged within the second syringe barrel slidingly displaceable from the back end towards the front end of the second syringe barrel;
wherein the second closed container is a third syringe barrel having a front end and a back end, wherein the front end of the third syringe barrel comprises the second closed container inlet and wherein the third moveable seal element comprises a third piston arranged within the third syringe barrel slidingly displaceable from the back end towards the front end of the third syringe barrel and connected to a third piston rod; and
wherein the second reservoir comprises a fourth syringe barrel having a front end and a back end, wherein the front end of the fourth

Assignees

• Omrix Biopharmaceuticals Ltd
• Ethicon Inc

Inventors

• Ilan Erez
• Regev Kfir
• Leitman Dana
• Nur Israel
• Meron Moti
• Goodman John

Classifications

• B01F35/7163

  the containers being connected in a mouth-to-mouth, end-to-end disposition, i.e. the openings are juxtaposed before contacting the contents · CPC title

• B01F33/50112

  of the syringe or cartridge type · CPC title

• B01F25/4512

  with reciprocating pistons · CPC title

• B01F33/251

  using balls as loose mixing element · CPC title

• B01F35/718

  using vacuum, under pressure in a closed receptacle or circuit system · CPC title