Patent · US10994045B2 · B2 · US

Process for making dry and stable hemostatic compositions

(11) Publication number

US10994045B2

(21) Application number

16/272,302

(22) Filing date

2019-02-11

(30) Priority date

2010-06-01

(43) Publication date

2021-05-04

(45) Date of grant

2021-05-04

(51) IPC

A61K 38/39; A61K 38/48; A61K 9/00; A61K 9/16; A61K 9/19; A61L 24/00; A61L 24/04; A61L 24/10; B32B 1/00; B65B 3/00; B65B 5/12; B65B 55/02

(52) CPC

A61L Methods or apparatus for sterilising materials or objects in general; disinfection, sterilisation or deodorisation of air; chemical aspects of bandages, dressings, absorbent pads or surgical articles; materials for bandages, dressings, absorbent pads or surgical articles: 24/043, 2300/418, 2300/802, 24/0015, 24/10, 24/106, 2400/04, 2400/06
A61K Preparations for medical, dental or toiletry purposes: 38/39, 38/4833, 9/0014, 9/06, 9/16, 9/1658, 9/19
A61P Specific therapeutic activity of chemical compounds or medicinal preparations: 17/02, 43/00, 7/04
B65B Machines, apparatus or devices for, or methods of, packaging articles or materials; unpacking: 3/003, 5/12, 55/02
C12Y Enzymes: 304/21005
Y10T Technical subjects covered by former us classification: 428/13

(73) Assignee

Baxter Healthcare SA; Baxter International Inc

(72) Inventors

Andreas Goessl; Atsushi Edward Osawa; Cary J. Reich

(54) Title

Process for making dry and stable hemostatic compositions

(57) Abstract

Described is a process for making a dry and stable hemostatic composition, said process comprising a) providing a first component comprising a dry preparation of a coagulation inducing agent, b) providing a second component comprising a dry preparation of a biocompatible polymer suitable for use in hemostasis, c) providing said first component and said second component in a combined form in a final container, c1) either by filling said first component and said second component into said final container so as to obtain a dry mixture in said final container, c2) or by providing said first component or said second component in said final container and adding said second component or said first component so as to obtain a combination of said first component with said second component in said final container, d) finishing the final container to a storable pharmaceutical device containing said first component and said second component in a combined form as a dry and stable hemostatic composition.

Full text

View on Google Patents

Claims (20)

A process for making a dry and stable hemostatic composition, said process comprising a) mixing in a solid state a first component comprising a dry preparation of a coagulation inducing agent and a second component comprising a dry preparation of a biocompatible polymer suitable for use in hemostasis to obtain said first component and said second component in a combined form, b) filling said first component and said second component in the combined form into a final container so as to obtain a dry mixture in said final container, and c) finishing the final container to a storable pharmaceutical device containing said first component and said second component in the dry mixture as a dry and stable hemostatic composition.
The process according to claim 1, wherein steps a) and b) are performed under aseptic conditions.
The process according to claim 1, wherein the dry preparation of a coagulation inducing agent is prepared by lyophilizing an aqueous preparation of a coagulation inducing agent.
The process according to claim 1, wherein step c) comprises an ethylene oxide sterilization step or a treatment with ionizing irradiation.
The process according to claim 1, wherein the first component is a dry thrombin preparation.
The process according to claim 1, wherein the first component is a dry particulate thrombin preparation.
The process according to claim 1, wherein the first component is a dry thrombin powder.
The process according to claim 1, wherein the first component contains thrombin obtained by spray drying or aseptic spray drying.
The process according to claim 1, wherein the final container is a syringe.
The process according to claim 9, wherein the syringe is a syringe finished together with a diluent syringe with a pharmaceutically acceptable diluent for reconstituting said dry and stable hemostatic composition.
The process according to claim 1, wherein the first component comprises human thrombin.
The process according to claim 1, wherein the first component comprises recombinant human thrombin.
The process according to claim 1, wherein the biocompatible polymer suitable for use in hemostasis contains a protein selected from the group consisting of gelatin, soluble collagen, albumin, hemoglobin, fibrinogen, fibrin, casein, fibronectin, elastin, keratin, and laminin; or derivatives or combinations thereof.
The process according to claim 1, wherein the biocompatible polymer suitable for use in hemostasis contains a polysaccharide selected from the group consisting of glycosaminoglycans, starch derivatives, cellulose derivatives, hemicellulose derivatives, xylan, agarose, alginate, and chitosan; or derivatives or combinations thereof.
The process according to claim 1, wherein the biocompatible polymer suitable for use in hemostasis contains a polymer selected from the group consisting of polyacrylates, polymethacrylates, polyacrylamides, polyvinyl resins, polylactide-glycolides, polycaprolactones, and polyoxyethlenes; and derivatives and combinations thereof.
The process according to claim 1, wherein the biocompatible polymer suitable for use in hemostasis contains a crosslinked polysaccharide, a crosslinked protein, or a crosslinked non-biologic polymer; or mixtures thereof.
The process according to claim 1, wherein the biocompatible polymer suitable for use in hemostasis is a particulate material.
The process according to claim 1, wherein the biocompatible polymer suitable for use in hemostasis is a granular material.
The process according to claim 1, wherein the biocompatible polymer suitable for use in hemostasis is a cross-linked gelatin.
The process according to claim 1, wherein the final container further contains an amount of a stabilizer effective to inhibit modification of the polymer when exposed to the sterilizing radiation, preferably ascorbic acid, sodium ascorbate, other salts of ascorbic acid, or an antioxidant.

Description

The present invention relates to processes for making hemostatic compositions in storage-stable form.

Hemostatic compositions in dry storage-stable form that comprise biocompatible, biodegradable, dry stable granular material are known e.g. from WO 98/008550 A or WO 2003/007845 A. These products have been successfully applied on the art for hemostasis. Floseal® is an example for a powerful and versatile hemostatic agent consisting of a granular gelatin matrix swollen in a thrombin-containing solution to form a flow-able paste.

Since such products have to be applied to humans, it is necessary to provide highest safety standards for quality, storage-stability and sterility of the final products and the components thereof. On the other hand, manufacturing and handling should be made as convenient and efficient as possible. If the Hemostatic compositions require a thrombin component for use, provision of this thrombin component in the final product is challenging. Since thrombin and the matrix material usually have different properties concerning manufacture requirements, they have to be manufactured and provided separately. For example, sterilization requirements may differ significantly between relatively stable granular (often also crosslinked) matrix material and proteinaceous components, such as thrombin. Whereas such matrix materials can usually be sterilized by powerful sterilization methods (such as autoclaving, gamma-irradiation, etc.), thrombin (as an enzyme) has to be treated with more care.

Citations (202)

US2507244A
US2558395A
US4124705A
JPS51125156A
US4013078A
US4164559A
US4347234A
US4265233A
US4179400A
US4291013A
US4377572A
US4298598A
US4362567A
US4300494A
US4292972A
US4554156A
US4453939A
US4424208A
US4536387A
US4482386A
US4543332A
US4540410A
JPS59113889A
EP0132983A1
EP0132983B2
US5061492A
US4515637A
US4640834A
US4600574A
US4837285A
WO1986000912A1
US4655211A
US4746514A
US4749689A
US5165938A
US5178883A
EP0376931A1
US5007916A
US4818517A
US5023082A
US5300494A
US4946870A
US4832686A
US4803075A
US5407671A
EP0282316A2
US4885161A
US4752466A
US5350573A
US5080893A
US5140016A
US5447966A
US5041292A
US4925677A
US5135751A
US5126141A
US5162430A
US5328955A
US5324775A
US5510418A
US5614587A
US4891359A
US5135755A
EP0493387A1
US5672336A
US5356614A
US5196185A
KR910007847A
US5061274A
US5219328A
US5134229A
US5149540A
US5306501A
US5595735A
US5017229A
US5209776A
US5292362A
US5275616A
US5108421A
US5192300A
US5275616B1
US5478352A
US5304377A
US5330446A
US5129882A
US6391343B1
US5690675A
WO1992021354A1
US5418222A
WO1992022252A1
US5714370A
US5352715A
US5204382A
US5428024A
US5384333A
US5507744A
US5512301A
US5399361A
JPH05308969A
US5648506A
US5385606A
US5540715A
US5428022A
US5514379A
US5520925A
EP0612252B1
US5437672A
US5667839A
JPH06254148A
WO1994027630A1
JPH0790241A
JPH09504719A
WO1995012371A1
WO1995015747A1
US5618551A
US5674275A
US5531759A
US5770229A
JPH0824325A
US5658592A
WO1996004025A1
US5853749A
US5516532A
WO1996006883A1
US5931165A
WO1996010428A1
WO1996010374A1
WO1996014368A1
US5698213A
US5580923A
WO1996039159A1
US6129761A
US5752974A
US5874500A
US6458889B1
US6166130A
US5959735A
US6649162B1
WO1997037694A1
EP0891193A1
WO1997044015A1
US5902832A
US7871637B2
US6066325A
US7320962B2
US6063061A
WO1998008550A1
US20080085316A1
US20020193448A1
US6458386B1
US5908054A
US6096309A
WO1999013902A1
US5997895A
US6179872B1
US6274090B1
US20070255238A1
US6277394B1
US6110484A
US6328229B1
US6312725B1
US6624245B2
US6706690B2
US6312474B1
EP1084720A1
CN1270240A
WO2001097871A2
WO2002022184A2
WO2002070594A2
WO2003007845A1
US20030064109A1
US20080286376A1
US7547446B2
US7435425B2
EP1414370B1
EP1283063A1
US20030224056A1
US20080109002A1
EP1484070A1
WO2004108179A1
US20060167561A1
US20060204490A1
US20060147492A1
US20050287215A1
WO2006031358A2
US20080091277A1
US20060088518A1
EP1649867A1
US20070225640A1
WO2006118460A1
WO2007001926A2
WO2007137839A3
WO2007137839A2
US20100028309A1
WO2008016983A2
US20090142396A1
WO2009123903A1
US20100292717A1
US20100318048A1
US20120021058A1
US20120128653A1
US9084728B2

Record as JSON

{
  "publication_number": "US10994045B2",
  "country": "US",
  "kind": "B2",
  "title": "Process for making dry and stable hemostatic compositions",
  "abstract": "Described is a process for making a dry and stable hemostatic composition, said process comprising a) providing a first component comprising a dry preparation of a coagulation inducing agent, b) providing a second component comprising a dry preparation of a biocompatible polymer suitable for use in hemostasis, c) providing said first component and said second component in a combined form in a final container, c1) either by filling said first component and said second component into said final container so as to obtain a dry mixture in said final container, c2) or by providing said first component or said second component in said final container and adding said second component or said first component so as to obtain a combination of said first component with said second component in said final container, d) finishing the final container to a storable pharmaceutical device containing said first component and said second component in a combined form as a dry and stable hemostatic composition.",
  "claims": [
    "1. A process for making a dry and stable hemostatic composition, said process comprising a) mixing in a solid state a first component comprising a dry preparation of a coagulation inducing agent and a second component comprising a dry preparation of a biocompatible polymer suitable for use in hemostasis to obtain said first component and said second component in a combined form, b) filling said first component and said second component in the combined form into a final container so as to obtain a dry mixture in said final container, and c) finishing the final container to a storable pharmaceutical device containing said first component and said second component in the dry mixture as a dry and stable hemostatic composition.",
    "2. The process according to claim 1, wherein steps a) and b) are performed under aseptic conditions.",
    "3. The process according to claim 1, wherein the dry preparation of a coagulation inducing agent is prepared by lyophilizing an aqueous preparation of a coagulation inducing agent.",
    "4. The process according to claim 1, wherein step c) comprises an ethylene oxide sterilization step or a treatment with ionizing irradiation.",
    "5. The process according to claim 1, wherein the first component is a dry thrombin preparation.",
    "6. The process according to claim 1, wherein the first component is a dry particulate thrombin preparation.",
    "7. The process according to claim 1, wherein the first component is a dry thrombin powder.",
    "8. The process according to claim 1, wherein the first component contains thrombin obtained by spray drying or aseptic spray drying.",
    "9. The process according to claim 1, wherein the final container is a syringe.",
    "10. The process according to claim 9, wherein the syringe is a syringe finished together with a diluent syringe with a pharmaceutically acceptable diluent for reconstituting said dry and stable hemostatic composition.",
    "11. The process according to claim 1, wherein the first component comprises human thrombin.",
    "12. The process according to claim 1, wherein the first component comprises recombinant human thrombin.",
    "13. The process according to claim 1, wherein the biocompatible polymer suitable for use in hemostasis contains a protein selected from the group consisting of gelatin, soluble collagen, albumin, hemoglobin, fibrinogen, fibrin, casein, fibronectin, elastin, keratin, and laminin; or derivatives or combinations thereof.",
    "14. The process according to claim 1, wherein the biocompatible polymer suitable for use in hemostasis contains a polysaccharide selected from the group consisting of glycosaminoglycans, starch derivatives, cellulose derivatives, hemicellulose derivatives, xylan, agarose, alginate, and chitosan; or derivatives or combinations thereof.",
    "15. The process according to claim 1, wherein the biocompatible polymer suitable for use in hemostasis contains a polymer selected from the group consisting of polyacrylates, polymethacrylates, polyacrylamides, polyvinyl resins, polylactide-glycolides, polycaprolactones, and polyoxyethlenes; and derivatives and combinations thereof.",
    "16. The process according to claim 1, wherein the biocompatible polymer suitable for use in hemostasis contains a crosslinked polysaccharide, a crosslinked protein, or a crosslinked non-biologic polymer; or mixtures thereof.",
    "17. The process according to claim 1, wherein the biocompatible polymer suitable for use in hemostasis is a particulate material.",
    "18. The process according to claim 1, wherein the biocompatible polymer suitable for use in hemostasis is a granular material.",
    "19. The process according to claim 1, wherein the biocompatible polymer suitable for use in hemostasis is a cross-linked gelatin.",
    "20. The process according to claim 1, wherein the final container further contains an amount of a stabilizer effective to inhibit modification of the polymer when exposed to the sterilizing radiation, preferably ascorbic acid, sodium ascorbate, other salts of ascorbic acid, or an antioxidant."
  ],
  "description_excerpt": "The present invention relates to processes for making hemostatic compositions in storage-stable form.\n\nHemostatic compositions in dry storage-stable form that comprise biocompatible, biodegradable, dry stable granular material are known e.g. from WO 98/008550 A or WO 2003/007845 A. These products have been successfully applied on the art for hemostasis. Floseal® is an example for a powerful and versatile hemostatic agent consisting of a granular gelatin matrix swollen in a thrombin-containing solution to form a flow-able paste.\n\nSince such products have to be applied to humans, it is necessary to provide highest safety standards for quality, storage-stability and sterility of the final products and the components thereof. On the other hand, manufacturing and handling should be made as convenient and efficient as possible. If the Hemostatic compositions require a thrombin component for use, provision of this thrombin component in the final product is challenging. Since thrombin and the matrix material usually have different properties concerning manufacture requirements, they have to be manufactured and provided separately. For example, sterilization requirements may differ significantly between relatively stable granular (often also crosslinked) matrix material and proteinaceous components, such as thrombin. Whereas such matrix materials can usually be sterilized by powerful sterilization methods (such as autoclaving, gamma-irradiation, etc.), thrombin (as an enzyme) has to be treated with more care.",
  "cpc": [
    "A61L 24/043",
    "A61K 38/39",
    "A61K 38/4833",
    "A61K 9/0014",
    "A61K 9/06",
    "A61K 9/16",
    "A61K 9/1658",
    "A61K 9/19",
    "A61L 2300/418",
    "A61L 2300/802",
    "A61L 24/0015",
    "A61L 24/10",
    "A61L 24/106",
    "A61L 2400/04",
    "A61L 2400/06",
    "A61P 17/02",
    "A61P 43/00",
    "A61P 7/04",
    "B65B 3/003",
    "B65B 5/12",
    "B65B 55/02",
    "C12Y 304/21005",
    "Y10T 428/13"
  ],
  "ipc": [
    "A61K 38/39",
    "A61K 38/48",
    "A61K 9/00",
    "A61K 9/16",
    "A61K 9/19",
    "A61L 24/00",
    "A61L 24/04",
    "A61L 24/10",
    "B32B 1/00",
    "B65B 3/00",
    "B65B 5/12",
    "B65B 55/02"
  ],
  "assignees": [
    "Baxter Healthcare SA",
    "Baxter International Inc"
  ],
  "inventors": [
    "Andreas Goessl",
    "Atsushi Edward Osawa",
    "Cary J. Reich"
  ],
  "filing_date": "2019-02-11",
  "publication_date": "2021-05-04",
  "grant_date": "2021-05-04",
  "priority_date": "2010-06-01",
  "application_number": "US-201916272302-A",
  "family_id": "44626900",
  "cited_by_count": 12,
  "citations": [
    "US2507244A",
    "US2558395A",
    "US4124705A",
    "JPS51125156A",
    "US4013078A",
    "US4164559A",
    "US4347234A",
    "US4265233A",
    "US4179400A",
    "US4291013A",
    "US4377572A",
    "US4298598A",
    "US4362567A",
    "US4300494A",
    "US4292972A",
    "US4554156A",
    "US4453939A",
    "US4424208A",
    "US4536387A",
    "US4482386A",
    "US4543332A",
    "US4540410A",
    "JPS59113889A",
    "EP0132983A1",
    "EP0132983B2",
    "US5061492A",
    "US4515637A",
    "US4640834A",
    "US4600574A",
    "US4837285A",
    "WO1986000912A1",
    "US4655211A",
    "US4746514A",
    "US4749689A",
    "US5165938A",
    "US5178883A",
    "EP0376931A1",
    "US5007916A",
    "US4818517A",
    "US5023082A",
    "US5300494A",
    "US4946870A",
    "US4832686A",
    "US4803075A",
    "US5407671A",
    "EP0282316A2",
    "US4885161A",
    "US4752466A",
    "US5350573A",
    "US5080893A",
    "US5140016A",
    "US5447966A",
    "US5041292A",
    "US4925677A",
    "US5135751A",
    "US5126141A",
    "US5162430A",
    "US5328955A",
    "US5324775A",
    "US5510418A",
    "US5614587A",
    "US4891359A",
    "US5135755A",
    "EP0493387A1",
    "US5672336A",
    "US5356614A",
    "US5196185A",
    "KR910007847A",
    "US5061274A",
    "US5219328A",
    "US5134229A",
    "US5149540A",
    "US5306501A",
    "US5595735A",
    "US5017229A",
    "US5209776A",
    "US5292362A",
    "US5275616A",
    "US5108421A",
    "US5192300A",
    "US5275616B1",
    "US5478352A",
    "US5304377A",
    "US5330446A",
    "US5129882A",
    "US6391343B1",
    "US5690675A",
    "WO1992021354A1",
    "US5418222A",
    "WO1992022252A1",
    "US5714370A",
    "US5352715A",
    "US5204382A",
    "US5428024A",
    "US5384333A",
    "US5507744A",
    "US5512301A",
    "US5399361A",
    "JPH05308969A",
    "US5648506A",
    "US5385606A",
    "US5540715A",
    "US5428022A",
    "US5514379A",
    "US5520925A",
    "EP0612252B1",
    "US5437672A",
    "US5667839A",
    "JPH06254148A",
    "WO1994027630A1",
    "JPH0790241A",
    "JPH09504719A",
    "WO1995012371A1",
    "WO1995015747A1",
    "US5618551A",
    "US5674275A",
    "US5531759A",
    "US5770229A",
    "JPH0824325A",
    "US5658592A",
    "WO1996004025A1",
    "US5853749A",
    "US5516532A",
    "WO1996006883A1",
    "US5931165A",
    "WO1996010428A1",
    "WO1996010374A1",
    "WO1996014368A1",
    "US5698213A",
    "US5580923A",
    "WO1996039159A1",
    "US6129761A",
    "US5752974A",
    "US5874500A",
    "US6458889B1",
    "US6166130A",
    "US5959735A",
    "US6649162B1",
    "WO1997037694A1",
    "EP0891193A1",
    "WO1997044015A1",
    "US5902832A",
    "US7871637B2",
    "US6066325A",
    "US7320962B2",
    "US6063061A",
    "WO1998008550A1",
    "US20080085316A1",
    "US20020193448A1",
    "US6458386B1",
    "US5908054A",
    "US6096309A",
    "WO1999013902A1",
    "US5997895A",
    "US6179872B1",
    "US6274090B1",
    "US20070255238A1",
    "US6277394B1",
    "US6110484A",
    "US6328229B1",
    "US6312725B1",
    "US6624245B2",
    "US6706690B2",
    "US6312474B1",
    "EP1084720A1",
    "CN1270240A",
    "WO2001097871A2",
    "WO2002022184A2",
    "WO2002070594A2",
    "WO2003007845A1",
    "US20030064109A1",
    "US20080286376A1",
    "US7547446B2",
    "US7435425B2",
    "EP1414370B1",
    "EP1283063A1",
    "US20030224056A1",
    "US20080109002A1",
    "EP1484070A1",
    "WO2004108179A1",
    "US20060167561A1",
    "US20060204490A1",
    "US20060147492A1",
    "US20050287215A1",
    "WO2006031358A2",
    "US20080091277A1",
    "US20060088518A1",
    "EP1649867A1",
    "US20070225640A1",
    "WO2006118460A1",
    "WO2007001926A2",
    "WO2007137839A3",
    "WO2007137839A2",
    "US20100028309A1",
    "WO2008016983A2",
    "US20090142396A1",
    "WO2009123903A1",
    "US20100292717A1",
    "US20100318048A1",
    "US20120021058A1",
    "US20120128653A1",
    "US9084728B2"
  ]
}

Record 1,654 of 8,000 in Patents full text (MLC-0201). Request the full dataset.