Method and apparatus for making mixtures of pharmaceutical liquids

• US 4,625,494 A
• Filed: 12/13/1985
• Issued: 12/02/1986
• Est. Priority Date: 04/28/1983
• Status: Expired due to Term

• Current Assignee: Pfrimmer + Company Pharmazeutische Werke Erlangen GmbH + Company KG
• Original Assignee: Pfrimmer + Company Pharmazeutische Werke Erlangen GmbH + Company KG
• Inventors: Iwatschenko, Peter, Giebler, Fritz
• Primary Examiner(s): Sipos, John
• Assistant Examiner(s): NOT, DEFINED
• Application Number:
  US06/808,668
• Time in Patent Office: 354 Days
• Field of Search: 53/86, 53/237, 53/434, 53/469, 53/474, 53/502, 53/512, 137/154, 137/205, 141/83, 141/94, 141/96, 141/100, 141/104, 141/105, 141/114, 141/315, 141/317, 604/80-83, 604/122, 604/245
• US Class Current: 53/432
• CPC Class Codes: A61J 2200/74 for weight
• CPC Class Codes: A61J 3/002 Compounding apparatus specially for enteral or parenteral nutritive solutions bottling liquids B67C
• CPC Class Codes: A61M 39/281 Automatic tube cut-off devices, e.g. squeezing tube on detection of air
• CPC Class Codes: A61M 5/1408 in parallel, e.g. manifolds, sequencing valves access sites A61M39/02; tube connectors A61M39/10
• CPC Class Codes: A61M 5/1409 in series, e.g. first substance passing through container holding second substance, e.g. reconstitution systems needle sets A61M5/162
• CPC Class Codes: A61M 5/16827 controlling delivery of multiple fluids, e.g. sequencing, mixing or via separate flow-paths infusion of multiple fluids without using a controller A61M5/1407
• CPC Class Codes: A61M 5/16881 Regulating valves on-off valves, e.g. clamps A61M39/28
• CPC Class Codes: B01F 2101/2202 Mixing compositions or mixers in the medical or veterinary field
• CPC Class Codes: B01F 33/84 Mixing plants with mixing receptacles receiving material dispensed from several component receptacles, e.g. paint tins
• CPC Class Codes: G01G 17/06 having means for controlling the supply or discharge
• CPC Class Codes: G05D 11/133 with discontinuous action

Abstract

Method for the preparation of mixtures of pharmaceutical liquids, for example infusion solutions, from storage containers containing at least two of the individual mixture components, in an arrangement with a vacuum chamber to receive the containers to be filled and with a connecting hose for each storage container as well as a tube connected to the container to be filled and also connected with the connection hoses of the storage containers via a hose connection, with the attainment of the desired predetermined amount of each mixture component being indicated by registering air intake into the individual connection hoses, clamping the respective connecting tube and sealing and cutting the hose downstream from the clamping following corresponding registration of air intake into all present connection hoses.

Claims

1. Apparatus for the automatic preparation and accurate mixing of predetermined amounts of pharmaceutical liquid contamination-free in a closed system, comprising a plurality of closed supply containers containing the liquid components to be mixed, a supply tube leading from each of said containers, a cannula connecting each respective supply container and supply tube, a connector means having a plurality of connector inlets and a connector outlet with each of said connector inlets being in communication with said connector outlet, each of said supply tubes being connected to one of said connector inlets of said connector means, a sensor means in each of said supply tubes located between said supply container and said connector means, said sensor means including means to sense emptying of the respective supply container by sensing air in the respective supply tube, closure means in each of said supply tubes located between said sensor means and said connector means and operable to close off the respective supply tube when said sensor means senses emptying of the respective supply container, a vacuum chamber, a receptacle to be filled with the mixed pharmaceutical liquid, said receptacle being disposed within said vacuum chamber, a conduit leading from said outlet connection of said connector means and passing sealingly into said vacuum chamber for connection to said receptacle, said cannulas, said supply tubes, said connector means, said conduit, and said receptacle being formed as a single connected unit which is packaged in a sterile condition, a sealing means located along said conduit downstream of said closure means and said connector means to seal said conduit after said receptacle receives the pharmaceutical liquid from said supply containers, whereby the apparatus is operable to pass the liquid simultaneously from all of said closed supply containers to said receptacle in said vacuum chamber along a sealed flow path sealed from the outside atmosphere while air is prevented from entering said receptacle upon emptying of the respective supply container by the sensor means which operates the respective closure means to close off the respective supply tube when air is present in the respective supply tube upon emptying of the respective supply container, the apparatus thereby providing for automatic and exact filling of the receptacle under sterile conditions.

2. Apparatus according to claim 1, wherein said sealing means comprises two sealing elements spaced from one another and operable to seal said conduit at two spaced locations, and cutting means located in said space between said two sealing elements for cutting said conduit between said two spaced locations.

3. Apparatus according to claim 2, wherein said sealing means comprises two metal sleeves, each situated around said conduit at said respective spaced locations.

4. Apparatus according to claim 2, wherein said sealing means is pneumatically actuated.

5. Apparatus according to claim 2, wherein said sealing means is hydraulicallly actuated.

6. Apparatus according to claim 1, wherein said sealing means is disposed outside said vacuum chamber.

7. Apparatus according to claim 1, wherein said sealing means is disposed inside said vacuum chamber.

8. Apparatus according to claim 1, wherein said closure means is magnetically actuated.

9. Apparatus for the automatic preparation and accurate mixing of predetermined amounts of pharmaceutical liquids contamination-free in a closed system, comprising a plurality of closed supply containers containing the liquid components to be mixed, a supply tube leading from each of said containers, a connector means having a plurality of connector inlets and a plurality of connector outlets with each of said connector inlets being in communication with each of said connector outlets, each of said supply tubes being connected to one of said connector inlets of said connector means, a sensor means in each of said supply tubes located between said supply container and said connector means, said sensor means including means to sense emptying of the respective supply container by sensing air in the respective supply tube, closure means in each of said supply tubes located between said sensor means and said connector means and operable to close off the respective supply tube when said sensor means senses emptying of the respective supply container, a vacuum chamber, a plurality of receptacles to be filled with the mixed pharmaceutical liquid, one of said receptacles being disposed within said vacuum chamber, a conduit connected to each of said connector outlets of said connector means and connected to each of said respective receptacles, one of said conduits connected to said one receptacle passing sealingly into said vacuum chamber, a scale means operable to weigh said one receptacle, a control means connected between said scale means and said closure means and operable to selectively open and close said closure means to effect sequential flow of predetermined amounts and weights of liquid from each of said supply containers into said one receptacle, and a sealing means located along said one conduit downstream of said closure means and said connector means to seal said one conduit after said one receptacle receives said predetermined amounts and weights of pharmaceutical liquids from said supply containers, whereby the apparatus is operable to sequentially pass predetermined amounts and weights of the pharmaceutical liquids from said supply containers to said one receptacle in said vacuum chamber in a flow path closed from the surrounding atmosphere, the apparatus also being operable to prevent air from entering said one receptacle upon eventual emptying of the respective supply container by the sensor means which operates the respective closure means to close off the respective supply tube when air is present in the respective supply tube upon emptying of the respective supply container, the apparatus thereby providing for automatic and exact filling of receptacles under sterile conditions, said one receptacle, upon receiving said predetermined amount of weights of pharmaceutical liquids and being sealed, being removed from said vacuum chamber and another of said receptacles connected to another of said conduits being placed into said vacuum chamber to receive predetermined amounts of weights of pharmaceutical liquids from said supply containers along a flow path which is closed and which was closed when said one receptacle was receiving said pharmaceutical liquids, whereby sterile conditions are maintained during filling of said plurality of receptacles, said other receptacle being precluded from receiving pharmaceutical liquids from said supply containers during filling of said one receptacle due to the differential pressure about said one and said other receptacle during filling of said one receptacle.

10. Apparatus according to claim 9, wherein said sealing means comprises two sealing elements spaced from one another and operable to seal said conduit at two spaced locations, and cutting means located in said space between said two sealing elements for cutting said conduit between said two spaced locations.

11. Apparatus according to claim 9, wherein said scale means is disposed in said vacuum chamber.

12. Apparatus according to claim 10, wherein said sealing means comprises two metal sleeves, each situated around said conduit at said respective spaced locations.

13. Apparatus according to claim 10, wherein said sealing means is pneumatically actuated.

14. Apparatus according to claim 9, wherein said sealing means is hydraulically actuated.

15. Apparatus according to claim 9, wherein said sealing means is disposed outside said vacuum chamber.

16. Apparatus according to claim 9, wherein said sealing means is disposed inside said vacuum chamber.

17. Apparatus according to claim 9, wherein said closure means comprises a magnetically actuated drive.

18. A method for automatically preparing and accurately mixing predetermined amounts of pharmaceutical liquids under sterile conditions, comprising the steps of passing the liquid to be mixed from separate closed supply containers along separate supply paths, combining said separate supply paths into a combined flow path leading to the receptacle to be filled with the pharmaceutical liquids, maintaining the outside of said receptacle under vacuum conditions, maintaining said separate supply paths and said combined flow path closed from the surrounding atmosphere, sensing the emptying of each of said supply containers by sensing means which sense the air in the respective separate supply path, closing off the respective supply path by closure means upon sensing said air to thereby prevent air from entering the supply path downstream of said closure means upon emptying of the respective supply container, and thereafter sealing off the contents of said receptacle, whereby the receptacle thereby receives a predetermined amount of pharmaceutical liquid from each of said supply containers along a flow path closed from the surrounding atmosphere and air is prevented from entering said receptacle upon emptying of the respective supply container, thereby providing for automatic and exact filling of the receptacle under sterile conditions.

19. A method for automatically preparing and accurately mixing predetermined amounts of pharmaceutical liquids under sterile conditions, comprising the steps of establishing separate supply paths for the liquid to be mixed, each of said supply paths leading from a separate closed supply container, combining said separate supply paths into a combined flow path leading to the receptacle to be filled with the liquids, maintaining the outside of said receptacle under vacuum conditions, maintaining said separate supply paths and said combined flow path closed from the surrounding atmosphere, initiating flow of pharmaceutical liquid from one of said supply containers along one of said separate supply paths to said receptacle by opening a first closure means in said one supply path, weighing said receptacle as the pharmaceutical liquid flows along said one supply path to said receptacle, closing off said one supply path by closing said first closure means after a predetermined amount and weight of pharmaceutical liquid has passed from said one supply container to said receptacle, initiating flow of pharmaceutical liquid from another of said supply containers along another of said separate supply paths to said receptacle by opening a second closure means in said other supply path, weighing said receptacle as the pharmaceutical liquid flows along said other supply path to said receptacle, closing off said other supply path by closing said second closure means after a predetermined amount and weight of pharmaceutical liquid has passed from said other supply container to said receptacle, repeating the aforesaid steps sequentially for each one of said supply containers and associated separate flow paths, sensing the eventual emptying of said supply containers by sensing means which sense air in the respective separate supply path, closing off the respective separate supply path by the respective closure means upon sensing the presence of air to thereby prevent air from entering the supply path downstream of the respective closure means upon emptying of the respective supply container, and thereafter sealing off the contents of said receptacle, whereby the receptacle thereby receives a predetermined amount and weight of pharmaceutical liquid from each of said supply containers along a flow path closed from the surrounding atmosphere and upon eventual emptying of each supply container, air is prevented form entering said receptacle, thereby providing for automatic and exact filling of the receptacle under sterile conditions.

20. Apparatus for the automatic preparation and accurate mixing of predetermined amounts of pharmaceutical liquids contamination-free in a closed system, comprising a plurality of closed supply containers containing the liquid components to be mixed, a supply tube leading from each of said containers, a connector means having a plurality of connector inlets and a plurality of connector outlets with each of said connector inlets being connected to each of said connector outlets, each of said supply tubes being connected to one of said connector inlets of said connector means, a sensor means in each of said supply tubes located between said supply container and said connector means, said sensor means including means to sense emptying of the respective supply container by sensing air in the respective supply tube, closure means in each of said supply tubes located between said sensor means and said connector means and operable to close off the respective supply tube when said sensor means senses emptying of the respective supply container, a vacuum chamber, a plurality of receptacles to be filled with the mixed pharmaceutical liquid, one of said receptacles being disposed within said vacuum chamber, a conduit connected to each of said outlet connections of said connector means and connected to each of said receptacles, respectively, one of said conduits connected to one of said receptacles passing sealingly into said vacuum chamber, a sealing means located along said one conduit downstream of said closure means and said connector means to seal said one conduit after said one receptacle receives the pharmaceutical liquid from said supply containers, whereby the apparatus is operable to pass the liquid simultaneously from all of said closed supply containers to said one receptacle in said vacuum chamber along a sealed flow path sealed from the outside atmosphere while air is prevented from entering said one receptacle upon emptying of the respective supply container by the sensor means which operates the respective closure means to close off the respective supply tube when air is present in the respective supply tube upon emptying of the respective supply container, the apparatus thereby providing for automatic and exact filling of said one receptacle under sterile conditions, said one receptacle, upon receiving said pharmaceutical liquid and being sealed, being removed from said vacuum chamber and another of said receptacles connected to another of said conduits being placed into said vacuum chamber to receive pharmaceutical liquid from said supply containers along a flow path which is closed and which was closed when said one receptacle was receiving said pharmaceutical liquid, whereby sterile conditions are maintained during filling of said plurality of receptacles, said other receptacle being precluded from receiving pharmaceutical liquids from said supply containers during filling of said one receptacle due to the differential pressure about said one and said other receptacle during filling of said one receptacle.

21. Apparatus for the automatic preparation and accurate mixing of predetermined amounts of pharmaceutical liquids contamination-free in a closed system, comprising a plurality of closed supply containers containing the liquid components to be mixed, a supply tube leading from each of said containers, a cannula connecting each respective supply container and supply tube, a connector means having a plurality of connector inlets and a connector outlet with each of said connector inlets being in communication with said connector outlet, each of said supply tubes being connected to one of said connector inlets of said connector means, a sensor means in each of said supply tubes located between said supply container and said connector means, said sensor means including means to sense emptying of the respective supply container by sensing air in the respective supply tube, closure means in each of said supply tubes located between said sensor means and said connector means and operable to close off the respective supply tube when said sensor means senses air in the respective supply tube, a vacuum chamber, a receptacle to be filled with the mixed pharmaceutical liquid, said receptacle being disposed within said vacuum chamber, a conduit leading from said connector outlet of said connector means and passing sealingly into said vacuum chamber for connection to said receptacle, said cannulas, said supply tubes, said connector means, said conduit, and said receptacle being formed as a single connected unit which is packaged in a sterile condition, a scale means operable to weigh said receptacle, a control means connected between said scale means and said closure means and operable to selectively open and close said closure means to effect sequential flow of predetermined amounts and weights of liquid from each of said supply containers into said receptacle, and a sealing means located along said conduit downstream of said closure means of said connector means to seal said conduit after said receptacle receives said predetermined amounts and weights of pharmaceutical liquids from said supply containers, whereby the apparatus is operable to sequentially pass predetermined amounts and weights of the pharmaceutical liquids from said supply containers to said receptacle in said vacuum chamber in a flow path closed from the surrounding atmosphere, the apparatus also being operable to prevent air from entering said receptacle upon eventual emptying of the respective supply container by the sensor means which operates the respective closure means to close off the respective supply tube when air is present in the respective supply tube upon emptying of the respective supply container, the apparatus thereby providing for automatic and exact filling of receptacles under sterile conditions.