US3616543A - Method of producing a multicomponent lyophilized product - Google Patents
Method of producing a multicomponent lyophilized product Download PDFInfo
- Publication number
- US3616543A US3616543A US873111A US3616543DA US3616543A US 3616543 A US3616543 A US 3616543A US 873111 A US873111 A US 873111A US 3616543D A US3616543D A US 3616543DA US 3616543 A US3616543 A US 3616543A
- Authority
- US
- United States
- Prior art keywords
- container
- frozen
- solution
- multicomponent
- lyophilized
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title abstract description 22
- 239000007788 liquid Substances 0.000 description 14
- 239000000203 mixture Substances 0.000 description 14
- 239000000243 solution Substances 0.000 description 13
- 230000008014 freezing Effects 0.000 description 7
- 238000007710 freezing Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 6
- 229940031348 multivalent vaccine Drugs 0.000 description 5
- 229930003270 Vitamin B Natural products 0.000 description 4
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 4
- 239000011720 vitamin B Substances 0.000 description 4
- 235000019156 vitamin B Nutrition 0.000 description 4
- 239000000126 substance Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 2
- 208000007502 anemia Diseases 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical group C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 2
- 229960000258 corticotropin Drugs 0.000 description 2
- 229960000304 folic acid Drugs 0.000 description 2
- 235000019152 folic acid Nutrition 0.000 description 2
- 239000011724 folic acid Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 101800000414 Corticotropin Proteins 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- 208000005647 Mumps Diseases 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940041323 measles vaccine Drugs 0.000 description 1
- 208000010805 mumps infectious disease Diseases 0.000 description 1
- 229940095293 mumps vaccine Drugs 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 201000005404 rubella Diseases 0.000 description 1
- 229960003131 rubella vaccine Drugs 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
Images
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65B—MACHINES, APPARATUS OR DEVICES FOR, OR METHODS OF, PACKAGING ARTICLES OR MATERIALS; UNPACKING
- B65B63/00—Auxiliary devices, not otherwise provided for, for operating on articles or materials to be packaged
- B65B63/08—Auxiliary devices, not otherwise provided for, for operating on articles or materials to be packaged for heating or cooling articles or materials to facilitate packaging
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
Definitions
- This invention relates to a method of packaging a plurality of lyophilized components in a single container in which no component is in contact with another component.
- the method finds its principle utility wherein incompatibility exists between any of the components in the presence of moisture.
- the invention also relates to the package produced by the novel process of this invention.
- An object of this invention is the provision of a dry product including two or more components each adjacent another arrayed about and adhered to the wall of a single container. Another object is the provision of a package consisting of a container having received therein at least two adjacent masses of lyophilized materials in which at least one of such masses includes a substance different from that contained in another of such masses. A special object is to provide a pharmaceutical package as described in which each of such masses includes a biological or physiological factor.
- multicomponent products useable in the novel procedure of this invention are those containing vitamin B an anti-anemia liver concentrate, and folic acid. Another system is adrenocorticotropin substances and vitamin B Additional examples are multivalent vaccines such as one containing measles, mumps and rubella antigens.
- the present invention obviates this shortcoming by providing that the various components are never in contact with one another either in the frozen, liquid or lyophilized states.
- the process of the present invention contemplates adding a solution of a first component to a container and freezing the solution on the wall of the container. The position of the container is then changed so that when a solution of a second component is added thereto it is adjacent but not touching the first frozen component. This second solution is then frozen in its position. This process is repeated for as many different components as required by the particular product.
- FIGS. 1 to 4 represent the process in two views.
- the container 1 with a means 2 for introducing a liquid composition is immersed in a freezing bath 3.
- a second liquid composition 5 is introduced slowly 6.
- FIG. 3 represents the container 1 with two frozen compositions 4 and 5 connected to a means 7 for applying a high vacuum for the lophilization step.
- FIG. 4 is a cross-sectional view of the container 1 with three frozen or lyophilized compositions 4, S and 8.
- An example of this method for preparing a multivalent vaccine involves adding to a sterilized 10 cc. pharmaceutical vial 1.5 ml. of sterile measles vaccine. The vial is then laid on its side in a freezer chest at a temperature of 60 C. until the liquid is frozen. The vial is rotated through and 1.52.0 ml. of sterile mumps vaccine is added and it is frozen as described above. The vial is rotated through another 120 and a third solution consisting of 1.5-2.0 ml. of rubella vaccine is added and then frozen. The contents of the vial is then lyophilized in the usual manner to provide a sterile, dry multivalent vaccine. The lyophilized product obtained in this process can be reconstituted with a liquid vehicle to produce a multivalent vaccine suitable for parenteral injection.
- a process for obtaining a package containing at least two masses of dry matter which comprises the steps of charging a first liquid composition into a container, freezing said composition, rotating said container about an axis, charging to said container a second liquid composition adjacent but not touching the frozen first composition, freezing said second liquid composition, and simultaneously lyophilizing the frozen masses.
- each of the materials charged into the container is a liquid composition of a pharmaceutical agent.
- each of the materials charged into the container is a liquid composition of an antigen suitable for use in a multivalent vaccine.
- one of the mate- References Cited rials charged into the container is a liquid composition UNITED STATES PATENTS of vitamin B wherein another of the materials is a solution or suspension of folic acid, and another of the 3 449 3 5 19 9 Starkey, J1" 34 5 materials is a solution or suspension of anti-anemia liver 5 concentrate.
- one of the mate- R C CAPOSSELA Assistant Examincr rials charged into the container is a liquid composition of adrenocorticotrophin and another of the materials C1 charged is a solution or suspension of vitamin B 10 6.
- the process of claim 1 wherein the container is 34-15; 6260; 206-47 A a glass pharmaceutical vial.
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Mechanical Engineering (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
A SOLUTION IS CHARGED TO A CONTAINER, THE SOLUTION IS FROZEN, THE CONTAINER IS ROTATED ABOUT AN AXIS IN SUCH A MANNER THAT SECOND SOLUTION INTRODUCED TO THE CONTAINER DOES NOT COME IN CONTACT WITH THE FROZEN FIRST SOLUTION AND THEN IT IS FROZEN. THIS PROCESS IS REPEATED AS OFTEN AS DESIRED OR AS OFTEN AS THE RELATIVE SIZED OF THE CONTAINER AND SOLUTION VOLUMES WILL PERMIT. THE FROZEN MASSES ARE THEN SIMULTANEOUSLY LYOPHILIZED.
Description
Nov. 2, 1971 E. s. BARCLAY 3,616,543
METHOD OF PRODUCING A MULTICOMPONENT LYOPHILIZED PRODUCT Filed Oct. 31, 1969 5 FIG.1 6
INVENTOR. EUGENE $.BARCLAY United States Patent 3,616,543 METHOD OF PRODUCING A MULTICOMPONENT LYOPHILIZED PRODUCT Eugene S. Barclay, West Chester, Pa., assignor to Merck & Co., Inc., Rahway, NJ. Filed Oct. 31, 1969, Ser. No. 873,111 Int. Cl. F26b 5/06 US. Cl. 34-5 6 Claims ABSTRACT OF THE DISCLOSURE A solution is charged to a container, the solution is frozen, the container is rotated about an axis in such a manner that a second solution introduced to the container does not come in contact with the frozen first solution and then it is frozen. This process is repeated as often as desired or as often as the relative sizes of the container and solution volumes will permit. The frozen masses are then simultaneously lyophilized.
This invention relates to a method of packaging a plurality of lyophilized components in a single container in which no component is in contact with another component. The method finds its principle utility wherein incompatibility exists between any of the components in the presence of moisture. The invention also relates to the package produced by the novel process of this invention.
An object of this invention is the provision of a dry product including two or more components each adjacent another arrayed about and adhered to the wall of a single container. Another object is the provision of a package consisting of a container having received therein at least two adjacent masses of lyophilized materials in which at least one of such masses includes a substance different from that contained in another of such masses. A special object is to provide a pharmaceutical package as described in which each of such masses includes a biological or physiological factor.
In industry in general, and particularly the chemical and pharmaceutical industries it is often desirable to supply products consisting of more than one component. Occasionally it is found that the components making up a given product are incompatible with each other to some extent either prohibiting their preparation as a single multicomponent system or at least shortening the storage life of the multicomponent product. In such cases it is necessary that the components be sold in separate containers and used individually or mixed immediately before use by the consumer. This is especially true in the pharmaceutical industry where the multicomponent products contain physiological or biological materials which are incompatible one with another, particularly when the products are to be given by injection.
Examples of multicomponent products useable in the novel procedure of this invention are those containing vitamin B an anti-anemia liver concentrate, and folic acid. Another system is adrenocorticotropin substances and vitamin B Additional examples are multivalent vaccines such as one containing measles, mumps and rubella antigens.
The prior art, US. Pat. 3,269,905, has attempted to solve this problem by admitting to a container a first com- Patented Nov. 2,, 1971 ponent, freezing, admitting a second component on top of the first, freezing, admitting a third component on top of the second and freezing and then lyophilizing the entire mass to produce a stratified lyophilized prodnot, each stratum being of a single component. This procedure has a shortcoming in that for a time during the process there is the possibility of interaction between two components at the interface between one frozen component and a newly added liquid component.
The present invention obviates this shortcoming by providing that the various components are never in contact with one another either in the frozen, liquid or lyophilized states. The process of the present invention contemplates adding a solution of a first component to a container and freezing the solution on the wall of the container. The position of the container is then changed so that when a solution of a second component is added thereto it is adjacent but not touching the first frozen component. This second solution is then frozen in its position. This process is repeated for as many different components as required by the particular product.
For a more detailed explanation of the invention reference is made to FIGS. 1 to 4. FIGS. 1 and 2 represent the process in two views. The container 1 with a means 2 for introducing a liquid composition is immersed in a freezing bath 3. After the first liquid composition 4 has been introduced and frozen, the container 1 is rotated, and a second liquid composition 5 is introduced slowly 6. FIG. 3 represents the container 1 with two frozen compositions 4 and 5 connected to a means 7 for applying a high vacuum for the lophilization step. FIG. 4 is a cross-sectional view of the container 1 with three frozen or lyophilized compositions 4, S and 8.
An example of this method for preparing a multivalent vaccine involves adding to a sterilized 10 cc. pharmaceutical vial 1.5 ml. of sterile measles vaccine. The vial is then laid on its side in a freezer chest at a temperature of 60 C. until the liquid is frozen. The vial is rotated through and 1.52.0 ml. of sterile mumps vaccine is added and it is frozen as described above. The vial is rotated through another 120 and a third solution consisting of 1.5-2.0 ml. of rubella vaccine is added and then frozen. The contents of the vial is then lyophilized in the usual manner to provide a sterile, dry multivalent vaccine. The lyophilized product obtained in this process can be reconstituted with a liquid vehicle to produce a multivalent vaccine suitable for parenteral injection.
What is claimed is:
1. A process for obtaining a package containing at least two masses of dry matter which comprises the steps of charging a first liquid composition into a container, freezing said composition, rotating said container about an axis, charging to said container a second liquid composition adjacent but not touching the frozen first composition, freezing said second liquid composition, and simultaneously lyophilizing the frozen masses.
2. The process of claim 1, wherein each of the materials charged into the container is a liquid composition of a pharmaceutical agent.
3. The process of claim 1, wherein each of the materials charged into the container is a liquid composition of an antigen suitable for use in a multivalent vaccine.
35 4 4. The process of claim 1 wherein one of the mate- References Cited rials charged into the container is a liquid composition UNITED STATES PATENTS of vitamin B wherein another of the materials is a solution or suspension of folic acid, and another of the 3 449 3 5 19 9 Starkey, J1" 34 5 materials is a solution or suspension of anti-anemia liver 5 concentrate. FREDERICK L. MATTESON, Primary Examiner 5. The process of claim 1, wherein one of the mate- R C CAPOSSELA Assistant Examincr rials charged into the container is a liquid composition of adrenocorticotrophin and another of the materials C1 charged is a solution or suspension of vitamin B 10 6. The process of claim 1 wherein the container is 34-15; 6260; 206-47 A a glass pharmaceutical vial.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US87311169A | 1969-10-31 | 1969-10-31 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3616543A true US3616543A (en) | 1971-11-02 |
Family
ID=25360993
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US873111A Expired - Lifetime US3616543A (en) | 1969-10-31 | 1969-10-31 | Method of producing a multicomponent lyophilized product |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US3616543A (en) |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3698201A (en) * | 1971-04-02 | 1972-10-17 | Katsuji Hirahara | Freeze molding slice material |
| US3789515A (en) * | 1970-10-30 | 1974-02-05 | Air Liquide | Apparatus for conditioning lyophilised products |
| US4162003A (en) * | 1973-06-30 | 1979-07-24 | Dezso Istvan Bartos | Ready-for-use rapid test package for serological tests |
| US4239746A (en) * | 1973-06-30 | 1980-12-16 | Dezso Istvan Bartos | Complement fixation test employing reactants in a disposable package |
| US4295280A (en) * | 1980-03-17 | 1981-10-20 | American Home Products Corporation | Method of obtaining a lyophilized product |
| US4351158A (en) * | 1980-01-22 | 1982-09-28 | American Home Products Corporation | Method of producing multicomponent lyophilized product |
| US4469228A (en) * | 1983-05-31 | 1984-09-04 | Schering Corporation | Interferon kit |
| US4712310A (en) * | 1986-09-15 | 1987-12-15 | E. I. Du Pont De Nemours And Company | Co-spray technique |
| EP0394050A2 (en) * | 1989-04-18 | 1990-10-24 | Sankyo Company Limited | A method of preparing a freeze-dried formulation containing a drug |
| AT509703A4 (en) * | 2010-09-22 | 2011-11-15 | Murray & Pool Entpr Ltd | PROCESS FOR STORING AND TRANSPORTING A FREEZER-DRIED PHYSIOLOGICALLY ACTIVE ACTIVE SUBSTANCE AND A LIQUID |
| US9795745B2 (en) | 2012-06-26 | 2017-10-24 | Bioneer A/S | Syringe with a hollow plunger |
-
1969
- 1969-10-31 US US873111A patent/US3616543A/en not_active Expired - Lifetime
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3789515A (en) * | 1970-10-30 | 1974-02-05 | Air Liquide | Apparatus for conditioning lyophilised products |
| US3698201A (en) * | 1971-04-02 | 1972-10-17 | Katsuji Hirahara | Freeze molding slice material |
| US4162003A (en) * | 1973-06-30 | 1979-07-24 | Dezso Istvan Bartos | Ready-for-use rapid test package for serological tests |
| US4239746A (en) * | 1973-06-30 | 1980-12-16 | Dezso Istvan Bartos | Complement fixation test employing reactants in a disposable package |
| US4351158A (en) * | 1980-01-22 | 1982-09-28 | American Home Products Corporation | Method of producing multicomponent lyophilized product |
| US4295280A (en) * | 1980-03-17 | 1981-10-20 | American Home Products Corporation | Method of obtaining a lyophilized product |
| US4469228A (en) * | 1983-05-31 | 1984-09-04 | Schering Corporation | Interferon kit |
| US4712310A (en) * | 1986-09-15 | 1987-12-15 | E. I. Du Pont De Nemours And Company | Co-spray technique |
| EP0394050A2 (en) * | 1989-04-18 | 1990-10-24 | Sankyo Company Limited | A method of preparing a freeze-dried formulation containing a drug |
| EP0394050A3 (en) * | 1989-04-18 | 1992-06-10 | Sankyo Company Limited | A method of preparing a freeze-dried formulation containing a drug |
| AT509703A4 (en) * | 2010-09-22 | 2011-11-15 | Murray & Pool Entpr Ltd | PROCESS FOR STORING AND TRANSPORTING A FREEZER-DRIED PHYSIOLOGICALLY ACTIVE ACTIVE SUBSTANCE AND A LIQUID |
| AT509703B1 (en) * | 2010-09-22 | 2011-11-15 | Murray & Pool Entpr Ltd | PROCESS FOR STORING AND TRANSPORTING A FREEZER-DRIED PHYSIOLOGICALLY ACTIVE ACTIVE SUBSTANCE AND A LIQUID |
| US9795745B2 (en) | 2012-06-26 | 2017-10-24 | Bioneer A/S | Syringe with a hollow plunger |
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