Claims:WE CLAIM:
1. A packaging unit (100) to package a tissue (1), comprising:
a. a primary packaging (110) including an inner tray (111) with an inner cavity (111a) to hold the tissue (1), and an inner lid (115) to seal the inner tray (111); and
b. a secondary packaging (130) including an outer tray (131) with an outer cavity (131b’) to hold the inner tray (111) and an outer lid (133) to seal the outer tray (131);
wherein,
a sheet (113) is disposed between the tissue (1) and the inner lid (115); and
the inner cavity (111a) and the outer cavity (131b’) include a predefined environment.
2. The packaging unit (100) as claimed in claim (1), wherein the pre-defined environment includes one of an oxidizing environment, a reducing environment, a low oxygen environment or an inert environment.
3. The packaging unit (100) as claimed in claim 1, wherein the sheet (113) include a plurality of perforations (113a) for even spread of a sterilant around the tissue (1).
4. The packaging unit (100) as claimed in claim 1, wherein the inner tray (111) and the outer tray (131) is made of a rigid or flexible medical grade plastic including one or more of polyethylene terephthalate glycol (PETG), Polyethylene terephthalate (PET), and acrylonitrile butadiene styrene (ABS).
5. The packaging unit (100) as claimed in claim 1, wherein the inner lid (115) and the outer lid (133) is made of a gas permeable or impermeable material including Tyvek, coated papers, nonporous foil laminates or other flexible films.
6. The packaging unit (100) as claimed in claim 1, wherein the sheet (113) is made of a material including one of aluminum, SS, CoCr, or metalized plastics.
7. A method (200) to package a tissue (1), the method comprising:
a. creating a predefined environment;
b. dehydrating a tissue (1);
c. placing the tissue (1) in an inner tray (111) of a primary packaging (110) of a packaging unit (100);
d. providing a sheet (113) over the tissue (1) in the primary packaging (110);
e. packaging the tissue (1) and the sheet (113) in the primary packaging (110);
f. sterilizing the primary packaging (110); and
g. sealing of the packaging unit (100) in a pouch.
8. The method (200) as claimed in claim 7, wherein before sealing the packaging unit (100) in a pouch, packaging the tissue (1) and the sheet (113) along with the primary packaging (110) in a secondary packaging (130) of the packaging unit (100).
9. The method (200) as claimed in claim 7, wherein the creating a pre-defined environment includes providing one of an oxidizing environment, a reducing environment, a low oxygen environment or an inert environment.
10. The method (200) as claimed in claim 7, wherein dehydrating the tissue (1) includes submerging the tissue (1) in an alcohol-polyol solution.
11. The method (200) as claimed in claim 7, wherein placing the tissue (1) in an inner tray (111) includes placing the tissue (1) within the inner cavity (111a) of the inner tray (111).
12. The method (200) as claimed in claim 7, wherein t sterilizing the primary packaging (110) includes subjecting the primary packaging (110) to a sterilization process including gas sterilization or radiation sterilization.
13. The method (200) as claimed in claim 7, wherein sealing of the packaging unit (100) in a pouch includes sealing the packaging unit (100) within a sterile pouch flushed with an inert gas.
14. The method (200) as claimed in claim 13, wherein sealing the packaging unit (100) within a sterile pouch flushed with an inert gas includes sealing the packaging unit (100) within a sterile aluminum pouch flushed with nitrogen.
15. A method (300) to package a tissue (1), the method comprising:
a. creating a predefined environment;
b. dehydrating a tissue (1);
c. placing the tissue (1) in an inner tray (111) of a primary packaging (110) of a packaging unit (100);
d. providing a sheet (113) over the tissue (1) in the primary packaging (110);
e. packaging the tissue (1) and the sheet (113) in the primary packaging (110);
f. packaging the tissue (1) and the sheet (113) along with the primary packaging (110) in a secondary packaging (130) of the packaging unit (100);
g. sterilizing the secondary packaging (130); and
h. sealing of the packaging unit (100) in a pouch.
16. The method (300) as claimed in claim 15, wherein the creating a pre-defined environment includes providing one of an oxidizing environment, a reducing environment, a low oxygen environment or an inert environment.
17. The method (300) as claimed in claim 15, wherein dehydrating the tissue (1) includes submerging the tissue (1) in an alcohol-polyol solution.
18. The method (300) as claimed in claim 15, wherein placing the tissue (1) in an inner tray (111) includes placing the tissue (1) within the inner cavity (111a) of the inner tray (111).
19. The method (300) as claimed in claim 15, wherein sterilizing the secondary packaging (130) includes subjecting the secondary packaging (130) to a sterilization process including gas sterilization or radiation sterilization.
20. The method (300) as claimed in claim 15, wherein sealing of the packaging unit (100) in a pouch includes sealing the packaging unit (100) within a sterile pouch flushed with an inert gas.
21. The method (300) as claimed in claim 20, wherein sealing the packaging unit (100) within a sterile pouch flushed with an inert gas includes sealing the packaging unit (100) within a sterile aluminum pouch flushed with nitrogen. , Description:FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
COMPLETE SPECIFICATION
(Section 10 and Rule 13)

1. TITLE OF THE INVENTION:
METHOD TO PACKAGE TISSUE WITHIN PACKAGING UNIT

2. APPLICANT:
Meril Life Sciences Pvt. Ltd., an Indian company of the address Survey No. 135/139 Bilakhia House, Muktanand Marg, Chala, Vapi- 396191, Gujarat, India

The following specification particularly describes the invention and the manner in which it is to be performed:

FIELD OF INVENTION
[001] The present invention relates to a packaging unit. More specifically, the present invention relates to a packaging unit used to package a tissue in a low oxygen environment.
BACKGROUND
[002] Bioprosthetic tissue and related devices such as heart valves, stent-grafts, and patches are typically stored in jars or containers with a preserving (storage) solution. Generally, glutaraldehyde is used as a storage solution because of its sterilant properties. Many other chemical agents having sterilant properties such as azides, aldehydes, carbimides, etc. can also be used for the storage of tissue based devices.
[003] However, if the jar containing the tissue in the preservation solution is exposed to light, the properties of the solution may get compromised resulting in either decomposition of the tissue or triggering its calcification property. Moreover, tissue stored within a preservation solution requires thorough saline rinsing before application as glutaraldehyde is a known carcinogen.
[004] Further, there is always a chance of contamination of the storage solution which results in unwanted growth of microbes thereby, diminishing tissue properties.
[005] Conventional solutions to the above described problems provide a packaging for dry tissues. However, the said packaging is vulnerable to severe oxidative stress during storage which results in deterioration of the tissue’s integrity. Further, any residual moisture and/or protective agent provided on the tissue seeps out through the packaging and/or the lid of the packaging rendering the tissue unacceptable for implantation.
[006] The dry tissue is sterilized by methods including ethylene oxide (EtO), gamma radiation, electron beam radiation, etc. However, EtO sterilization reveals that the tissue endures increased temperatures and water vapor which causes oxidative damage to the tissue. Whereas, gamma radiation generates reactive oxygen species in the collagenous substrates of the tissue which induces backbone scission causing damage to the collagen fibrils. This damage tends to compromise mechanical and biochemical function of the tissue. Similarly, electron-beam irradiation splits the collagen backbone causing deterioration of the tissue structure. This damage from oxidation through sterilization and, to some extent, during storage may lead to tissue/valve deterioration and structural failure.
[007] Therefore, there arises a requirement of a packaging unit which overcomes the aforementioned challenges associated with the conventional packaging.
SUMMARY
[008] The present invention relates to a packaging unit used to package a tissue. The packaging unit includes a primary packaging having an inner tray with an inner cavity to hold the tissue, and an inner lid to seal the inner tray. The packaging unit further includes a secondary packaging having an outer tray with an outer cavity to hold the inner tray and an outer lid to seal the outer tray. A sheet is disposed between the tissue and the inner lid. The inner cavity and the outer cavity include a predefined environment.
[009] The present invention also relates to a method to package a tissue. The method including creating a predefined environment, dehydrating a tissue, placing the tissue in an inner tray of a primary packaging of a packaging unit, providing a sheet over the tissue in the primary packaging, packaging the tissue and the sheet in the primary packaging, sterilizing the primary packaging, and sealing of the packaging unit in a pouch.
[0010] The present invention relates to another method to package a tissue. The method including creating a predefined environment, dehydrating a tissue, placing the tissue in an inner tray of a primary packaging of a packaging unit, providing a sheet over the tissue in the primary packaging, packaging the tissue and the sheet in the primary packaging, packaging the tissue and the sheet along with the primary packaging in a secondary packaging of the packaging unit, sterilizing the secondary packaging and sealing of the packaging unit in a pouch.
[0011] The foregoing features and other features as well as the advantages of the invention will become more apparent from the following detailed description, which proceeds with reference to the accompanying figures.
BRIEF DESCRIPTION OF DRAWINGS
[0012] The summary above, as well as the following detailed description of illustrative embodiments, is better understood when read in conjunction with the apportioned drawings. For the purpose of illustrating the present disclosure, exemplary constructions of the disclosure are shown in the drawings. However, the disclosure is not limited to specific methods and instrumentalities disclosed herein. Moreover, those in the art will understand that the drawings are not to scale.
[0013] Fig. 1 depicts an exploded view of a packaging unit 100 for a tissue 1 in accordance with an embodiment of the present invention.
[0014] Fig. 1a depicts a top view of a packaging unit 100 for the tissue 1 in accordance with an embodiment of the present invention.
[0015] Fig. 2 depicts an exploded view of a quadrilateral primary packaging 110 for a heart valve 2 in accordance with an embodiment of the present invention.
[0016] Fig. 3 illustrates a flowchart of a method 200 to package the tissue 1 (and/or heart valve 2) in the packaging unit 100 in accordance with an embodiment of the present invention.
[0017] Fig. 4 illustrates a flowchart of a method 300 to package the tissue 1 (and/or heart valve 2) in the packaging unit 100 in accordance with an embodiment of the present invention.
DETAILED DESCRIPTION OF THE DRAWINGS
[0018] Prior to describing the invention in detail, definitions of certain words or phrases used throughout this patent document will be defined: the terms "include" and "comprise", as well as derivatives thereof, mean inclusion without limitation; the term "or" is inclusive, meaning and/or; the phrases "coupled with" and "associated therewith", as well as derivatives thereof, may mean to include, be included within, interconnect with, contain, be contained within, connect to or with, couple to or with, be communicable with, cooperate with, interleave, juxtapose, be proximate to, be bound to or with, have a property of, or the like; Definitions of certain words and phrases are provided throughout this patent document, and those of ordinary skill in the art will understand that such definitions apply in many, if not most, instances to prior as well as future uses of such defined words and phrases.
[0019] Reference throughout this specification to “one embodiment,” “an embodiment,” or similar language means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, appearances of the phrases “in one embodiment,” “in an embodiment,” and similar language throughout this specification may, but do not necessarily, all refer to the same embodiment, but mean “one or more but not all embodiments” unless expressly specified otherwise. The terms “including,” “comprising,” “having,” and variations thereof mean “including but not limited to” unless expressly specified otherwise. An enumerated listing of items does not imply that any or all of the items are mutually exclusive and/or mutually inclusive, unless expressly specified otherwise. The terms “a,” “an,” and “the” also refer to “one or more” unless expressly specified otherwise.
[0020] Although the operations of exemplary embodiments of the disclosed method may be described in a particular, sequential order for convenient presentation, it should be understood that the disclosed embodiments can encompass an order of operations other than the particular, sequential order disclosed. For example, operations described sequentially may in some cases be rearranged or performed concurrently. Further, descriptions and disclosures provided in association with one particular embodiment are not limited to that embodiment, and may be applied to any embodiment disclosed herein. Moreover, for the sake of simplicity, the attached figures may not show the various ways in which the disclosed system, method, and apparatus can be used in combination with other systems, methods, and apparatuses.
[0021] Furthermore, the described features, advantages, and characteristics of the embodiments may be combined in any suitable manner. One skilled in the relevant art will recognize that the embodiments may be practiced without one or more of the specific features or advantages of a particular embodiment. In other instances, additional features and advantages may be recognized in certain embodiments that may not be present in all embodiments. These features and advantages of the embodiments will become more fully apparent from the following description and apportioned claims, or may be learned by the practice of embodiments as set forth hereinafter.
[0022] In accordance with the present disclosure, a packaging unit and corresponding method used to package a tissue in a predefined environment is disclosed. The tissue may be an animal tissue utilized for medical applications such as in artificial heart valves, stent-grafts, patches, aortic valve conduits etc. In an embodiment, the tissue is a bovine pericardium tissue.
[0023] The packaging unit of the present invention includes a tray having a predefined shape and a corresponding lid to cover the tray. The tray may be utilized to enclose the tissue with the aid of the lid. Further, the packaging unit may include a sheet disposed between the tray and the lid. In an embodiment of the present invention, the sheet is placed over the tissue (placed in the tray) before covering the tray with the lid. The sheet prevents absorption/seepage of any residual solvent/chemical present on the tissue through the lid thereby improving shelf-life of the tissue without any change in tissue integrity. Further, the risk of contamination of the tissue is reduced as the tissue does not come in direct contact with the lid.
[0024] The packaging unit may be gas sterilized. During gas sterilization, a plurality of perforations provided on the sheet ensures even spread of the sterilization gas around the tissue thereby facilitating efficient sterilization of the tissue.
[0025] The packaging unit preserves tissue integrity and properties for a long span of time. Further, the packaging unit provides an easy to handle, easy to assemble and/or microbe free packaging of the tissue. The packaging unit as disclosed in the present invention overcomes the calcification reactions and toxicity of conventional storage solution (like glutaraldehyde) while maintaining quality of the tissue.
[0026] The tissue may be packaged in the packaging unit in a low oxygen environment. The low oxygen environment prevents oxidative damage of the tissue and enhances its shelf life.
[0027] Now referring specifically to drawings, Fig. 1 depicts a packaging unit 100 used to package a tissue 1. The tissue 1 may be a bovine pericardium tissue.
[0028] The packaging unit 100 may include one or more layers of packaging. In an embodiment, the packaging unit 100 includes a double layered packaging namely, a primary packaging 110 and a secondary packaging 130. Alternatively, the packaging unit 100 may include only the primary packaging 110. The primary packaging 110 and the secondary packaging 130 together provide a dual barrier/seal thereby further reducing any risk of microbial contamination.
[0029] The primary packaging 110 may include an inner tray 111, a sheet 113 and an inner lid 115. The inner tray 111 may be made of any rigid or flexible medical grade plastic including but not limited to polyethylene terephthalate glycol (PETG), Polyethylene terephthalate (PET), acrylonitrile butadiene styrene (ABS), etc. In an embodiment, the inner tray 111 is made of rigid PETG owing to its high melting temperature.
[0030] The packaging unit 100 may have any shape and dimension. The shape and dimension of the packaging unit 100 may vary according to the shape and size of the tissue 1 and/or other parameters including but not limited to controlling movement of the tissue 1, sterilant penetration within the packaging unit 100 for sterilization and easy handling of the packaging unit 100 and/or tissue 1. The inner tray 111 may have a length ranging from 150mm to 250mm. The inner tray 111 may have a width ranging from 100mm to 200mm. In an embodiment, the length and width of the inner tray 111 is 197mm and 148.6mm respectively.
[0031] The inner tray 111 may be defined by an extruded perimeter 111’. The inner tray 111 may include a plurality of sides to define a two-dimensional shape. In an embodiment (depicted in Fig. 1 and 1a), the inner tray 111 includes five sides defining a pentagonal shape. In an alternate embodiment (depicted in Fig. 2), the inner tray 111 includes four sides defining a quadrilateral shape.
[0032] The inner tray 111 may include at least one inner cavity 111a to hold the tissue 1. In an embodiment, the inner tray 111 includes the inner cavity 111a disposed at a center of the inner tray 111. The inner cavity 111a may have any shape and dimension corresponding to the size of the tissue 1. In an embodiment (depicted in Fig. 1 and 1a), the inner cavity 111a is elliptical in shape to hold the tissue 1. The inner cavity 111a may have a diameter ranging from 95mm to 110mm. In an embodiment, the diameter of the inner cavity 111a is 102mm. The inner cavity 111a may have a depth ranging from 01mm to 10mm. In an embodiment, the depth of the inner cavity 111a is 3mm. The inner cavity 111a may provide a snug or loose fit to the tissue 1. In an embodiment, the inner cavity 111a provides a snug fit to the tissue 1. The inner cavity 111a helps in restricting any stray movement of the tissue 1 while handling and transportation of the packaging unit 100.
[0033] The inner cavity 111a of the primary packaging 110 may include a pre-defined environment including but not limited to an oxidizing environment, a reducing environment, a low oxygen environment, or an inert environment. In an embodiment, the inner cavity 111a includes an oxidizing environment with 8-10% of oxygen.
[0034] Optionally, the inner tray 111 may include one or more inner side panels 111b (as shown in Fig. 1 and 1a). The inner side panel 111b may make an angle ‘i’ with the extruded perimeter 111’ of the inner tray 111 (shown in Fig. 1a). The angle ‘i’ may range from 60 degree to 90 degree. In an embodiment, the angle ‘i’ is 75 degree. The inner side panel 111b helps in easy handling of the primary packaging 110.
[0035] In an alternate embodiment (depicted in Fig. 2), the inner cavity 111a is shaped as a rounded square to hold a tissue based prosthetic heart valve 2. The inner cavity 111a may have a dimension corresponding to the size of the heart valve 2. The inner cavity 111a may include one or more extruded hubs 111a’ to further hold the heart valve 2. The inner cavity 111a along with the extruded hub 111a’ helps in restricting any stray movement of the heart valve 2 while handling and transportation of the packaging unit 100.
[0036] The tissue 1 and/or heart valve 2 may be placed within the inner cavity 111a of the inner tray 111 sealed with the inner lid 115 (described below). The sheet 113 may be disposed between the tissue 1 and the inner lid 115. The sheet 113 may prevent absorption/seepage of any residual solvent/chemical present on the tissue 1 through the lid thereby improving shelf-life of the tissue 1 without any change in tissue integrity. Further, the risk of contamination of the tissue 1 is reduced as the tissue 1 does not come in direct contact with the inner lid 115 due to the sheet 113.
[0037] The sheet 113 may be made of a material including but not limited to aluminum, SS, CoCr, metalized plastics, etc. In an embodiment, the sheet 113 is made of aluminum. The sheet 113 may have a shape and dimension corresponding to the dimensions of the inner tray 111. In an embodiment, the sheet 113 is shaped corresponding to the extruded perimeter 111’ of the inner tray 111. The sheet 113 may have a length ranging from 2cm to 20cm. The sheet 113 may have a width ranging from 2cm to 20 cm. In an embodiment, the length and width of the sheet 113 is 125mm and 165mm respectively. In an alternate embodiment, the sheet 113 is shaped corresponding to the inner cavity 111a.
[0038] The sheet 113 may also have a thickness ranging from 10 microns to 20 microns. In an embodiment, the thickness of the sheet 113 is 16 microns. A plurality of edges of the sheet 113 may be contoured towards the inner tray 111 to stabilize the sheet 113 over the inner tray 111.
[0039] The sheet 113 may include a plurality of perforations 113a arranged in any random or uniform order. The perforation 113a may have any shape. In an embodiment, the perforation 113a is circular in shape and disposed uniformly over the entire sheet 113. The perforation 113a may have a diameter ranging from 0.5mm to 30mm. In an embodiment, the diameter of the perforation 113a is 3mm. During gas sterilization, the perforations 113a ensure even spread of gas or any other sterilant around the tissue 1 for efficient sterilization.
[0040] The inner tray 111 may be sealed by the inner lid 115. The inner lid 115 may be mounted over the inner tray 111 and sealed by pressure heat sealing process. The pressure heat sealing process may be performed in a blister sealing machine.
[0041] The inner lid 115 may be made of a gas permeable or impermeable material including but not limited to Tyvek, coated papers, nonporous foil laminates and other flexible films. In an embodiment, the inner lid 115 is made of gas permeable Tyvek. The inner lid 115 may have any shape and dimension corresponding to the inner tray 111. In an embodiment, the inner lid 115 is shaped corresponding to the extruded perimeter 111’ of the inner tray 111. The inner lid 115 enables the sterilization gas to pass through while restricting microbial movement across the inner lid 115.
[0042] The primary packaging 110 may be housed within the secondary packaging 130 of the packaging unit 100. The secondary packaging 130 may include an outer tray 131 and an outer lid 133. The outer tray 131 may be made of any rigid or flexible medical grade plastic including but not limited to polyethylene terephthalate glycol (PETG), Polyethylene terephthalate (PET), acrylonitrile butadiene styrene (ABS), etc. In an embodiment, the outer tray 131 is made of rigid PETG. The outer tray 131 may have any shape and dimension corresponding to the primary packaging 110. The outer tray 131 may have a length ranging from 250mm to 300mm. The outer tray 131 may have a width ranging from 150 to 200. In an embodiment, the length and width of the outer tray 131 is 270mm and 180mm respectively.
[0043] The outer tray 131 may include a one or more stepped extruded perimeter. In an embodiment, the outer tray 131 includes a two-step extruded perimeter namely, an outer step 131a and an inner step 131b. The outer tray 131 may be defined by the outer step 131a. The outer tray 131 may include a plurality of sides to define a two-dimensional shape corresponding to the inner tray 111.
[0044] The inner step 131b may define an outer cavity 131b’. The outer cavity 131b’ may have any dimension corresponding to the dimensions of the inner tray 111. The outer cavity 131b’ may have a length ranging from 200 mm to 300mm. The outer cavity 131b’ may have a width ranging from 150mm to 230mm. In an embodiment, the length and width of the outer cavity 131b’ is 265mm and 180 mm respectively.
[0045] The outer cavity 131b’ of the primary packaging 110 may include a pre-defined environment including but not limited to a oxidizing environment, a reducing environment, a low oxygen environment, an inert environment. In an embodiment, the outer cavity 131b’ includes 8-10% of oxygen.
[0046] The inner tray 111 may be placed over the inner step 131b. The outer step 131a may prevent any stray movement of the inner tray 111 while handling and transportation of the packaging unit 100.
[0047] Optionally, the outer tray 131 may also include one or more outer side panels 131c (as shown in Fig. 1 and 1a). The outer side panel 131c may make an angle ‘o’ with the outer step 131a of the outer tray 131 (shown in Fig.1a). The angle ‘o’ may range from 45degree to 80degree. In an embodiment, the angle ‘o’ is 60 degree. The outer side panel 131c helps in easy handling of the secondary packaging 130.
[0048] The outer tray 131 may be sealed by the outer lid 133. The outer lid 133 may be mounted over the inner tray 111 and sealed by pressure heat sealing process. The pressure heat sealing process may be performed in a blister sealing machine.
[0049] The outer lid 133 may be made of a gas permeable or impermeable material including but not limited to Tyvek, coated papers, nonporous foil laminates and other flexible films. In an embodiment, the outer lid 133 is made of gas permeable Tyvek. The outer lid 133 may have any shape and dimension corresponding to the outer tray 131. In an embodiment, the outer lid 133 is shaped corresponding to the outer step 131a of the outer tray 131. The outer lid 133 enables the sterilization gas to pass through while restricting microbial movement across the outer lid 133.
[0050] The packaging unit 100 may further be sealed in a pouch made of a gas permeable or impermeable material including but not limited to Tyvek, aluminum, coated papers, nonporous foil laminates and other flexible films. In an embodiment, the packaging unit 100 is sealed within a gas impermeable aluminum pouch (not shown). The pouch may be flushed with an inert gas before sealing the pouch. In an embodiment, the pouch is flushed with nitrogen before sealing. The inert atmosphere within the pouch will prevent any potential oxidative damage to the tissue 1 during storage while preserving its fundamental properties.
[0051] Fig. 3 is a flowchart illustrating a method 200 used to package the tissue 1 (and/or heart valve 2) in the packaging unit 100. The tissue 1 may be pre-processed with one or more chemical agents/solutions before packaging. The one or more chemical agents/solutions may be used for tissue fixation, anti-calcification treatment, etc.
[0052] The method 200 begins at step 201, where a predefined environment is created. In an embodiment, a low oxygen environment is created. The low oxygen environment corresponds to an environment having oxygen concentration ranging from 8% to 10%. In an embodiment, the oxygen concentration in the low oxygen environment is 8%. The low oxygen environment may be maintained by any known methods like by purging an inert gas (for example, nitrogen) within a laminar air flow (LAF) chamber or a clean room. The low oxygen environment created prevents oxidative damage to the tissue 1 during sterilization and/or storage of the tissue 1.
[0053] At step 203, the tissue 1 may be dehydrated. Dehydrating a tissue corresponds to a tissue and/or a tissue based device (bioprosthesis) having reduced moisture content on a tissue surface, preferably around 20%. This 20% moisture is necessary for maintaining tissue integrity and its fundamental properties. Further, a bulk of the tissue and/or the tissue based device (bioprosthesis) may also be free of any excessive fixative agent (such as glutaraldehyde) thereby existing in a “dry” state instead of a “wet” state with excessive glutaraldehyde.
[0054] The tissue 1 may be dehydrated by submerging the tissue 1 in an alcohol-polyol solution. Thereafter, the tissue 1 may be dried to remove any excess moisture and/or alcohol-polyol solution. The alcohol used for dehydration may include but not limited to ethanol, methanol, ether, etc. The polyol used for dehydration may include but not limited to glycerol, polyethylene gycol, sorbitol, mannitol etc.
[0055] In an embodiment, the tissue is dehydrated by submerging the tissue in an ethanol-glycerol mixture having a % ratio of 25:75 and then air dried in an air-lap within a clean hood. The alcohol-polyol solution prevents oxidation of the tissue during sterilization as well as storage. Moreover, by dehydrating the tissue 1, the tissue 1 can be stored without any toxic preserving solution and does not require thorough rinsing with saline solution before application (during surgery). The tissue 1 is rendered as a ready to use device which reduces surgery and preparation time without compromising on any risks of contamination.
[0056] At step 205, the tissue 1 may be placed within the inner cavity 111a of the inner tray 111 and the sheet 113 may be placed over the tissue 1. Thereafter the inner tray 111 of the primary packaging 110 may be sealed with the inner lid 115. The sheet 113 prevents absorption/seepage of any residual solvent/chemical present on the tissue 1 through the inner lid 115 thereby improving shelf-life of the tissue 1 without any change in tissue integrity.
[0057] At step 207, the primary packaging 110 may be subjected to a sterilization process including but not limited to gas sterilization, radiation sterilization, etc. In an embodiment, the primary packaging 110 is sterilized by 100% Ethylene Oxide gas (sterilant) in a predefined environment. In an exemplary embodiment, the sterilization process is carried out at 42 ± 3°C temperature, relative humidity (%RH) less than or equal to 40%, vacuum pressure set point less than 160mbar, aeration time 140-200minutes and exposure time 120-280 minutes. During gas sterilization, the perforations 113a of the sheet 113 ensure even spread of gas around the tissue 1 for efficient sterilization.
[0058] At an optional step 209, the inner tray 111 may be placed over the inner step 131b of the outer tray 131. Further, the outer tray 131 of the secondary packaging 130 may be sealed with the outer lid 133.
[0059] At step 211, the primary packaging 110 alone and/or the primary packaging 110 along with the secondary packaging 130 may be sealed inside a sterile pouch flushed with an inert gas. In an embodiment, the packaging unit 100 is sealed inside an aluminum pouch having a low oxygen environment. The low oxygen environment inside the aluminum pouch may be generated by flushing the aluminum pouch with nitrogen or other functionally equivalent means. The low oxygen environment inside the pouch prevents any oxidative damage of the tissue 1 thereby enhances the shelf life of the tissue 1 without damaging the packaging unit 100.
[0060] Fig. 4 is a flowchart illustrating another method 300 used to package the tissue 1 (and/or heart valve 2) in the packaging unit 100. The tissue 1 may be pre-processed with one or more chemical agents/solutions before packaging. The one or more chemical agents/solutions may be used for tissue fixation, anti-calcification treatment, etc.
[0061] The method 300 begins at step 301, where a predefined environment is created. In an embodiment, a low oxygen environment is created. The low oxygen environment corresponds to an environment having oxygen concentration ranging from 8% to 10%. In an embodiment, the oxygen concentration in the low oxygen environment is 8%. The low oxygen environment may be maintained by any known methods like by purging an inert gas (for example, nitrogen) within a laminar air flow (LAF) chamber or a clean room. The low oxygen environment created prevents oxidative damage to the tissue 1 during sterilization and/or storage of the tissue 1.
[0062] At step 303, the tissue 1 may be dehydrated. Dehydrating a tissue corresponds to a tissue and/or a tissue based device (bioprosthesis) having reduced moisture content on a tissue surface, preferably around 20%. This 20% moisture is necessary for maintaining tissue integrity and its fundamental properties. Further, a bulk of the tissue and/or the tissue based device (bioprosthesis) may also be free of any excessive fixative agent (such as glutaraldehyde) thereby existing in a “dry” state instead of a “wet” state with excessive glutaraldehyde.
[0063] The tissue 1 may be dehydrated by submerging the tissue 1 in an alcohol-polyol solution. Thereafter, the tissue 1 may be dried to remove any excess moisture and/or alcohol-polyol solution. The alcohol used for dehydration may include but not limited to ethanol, methanol, ether, etc. The polyol used for dehydration may include but not limited to glycerol, polyethylene gycol, sorbitol, mannitol etc.
[0064] In an embodiment, the tissue is dehydrated by submerging the tissue in an ethanol-glycerol mixture having a % ratio of 25:75 and then air dried in an air-lap within a clean hood. The alcohol-polyol solution prevents oxidation of the tissue during sterilization as well as storage. Moreover, by dehydrating the tissue 1, the tissue 1 can be stored without any toxic preserving solution and does not require thorough rinsing with saline solution before application (during surgery). The tissue 1 is rendered as a ready to use device which reduces surgery and preparation time without compromising on any risks of contamination.
[0065] At step 305, the tissue 1 may be placed within the inner cavity 111a of the inner tray 111 and the sheet 113 may be placed over the tissue 1. Thereafter the inner tray 111 of the primary packaging 110 may be sealed with the inner lid 115. The sheet 113 prevents absorption/seepage of any residual solvent/chemical present on the tissue 1 through the inner lid 115 thereby improving shelf-life of the tissue 1 without any change in tissue integrity.
[0066] At step 307, the inner tray 111 may be placed over the inner step 131b of the outer tray 131. Further, the outer tray 131 of the secondary packaging 130 may be sealed with the outer lid 133.
[0067] At step 309, the secondary packaging 130 may be subjected to a sterilization process including but not limited to gas sterilization, radiation sterilization, etc. In an embodiment, the secondary packaging 130 is sterilized by 100% Ethylene Oxide gas (sterilant) in a predefined environment. In an exemplary embodiment, the sterilization process is carried out at 42 ± 3°C temperature, relative humidity (%RH) less than or equal to 40%, vacuum pressure set point less than 160mbar, aeration time 140-200minutes and exposure time 120-280 minutes. During gas sterilization, the perforations 113a of the sheet 113 ensure even spread of gas around the tissue 1 for efficient sterilization.
[0068] At step 311, the packaging unit 100 may be sealed inside a sterile pouch flushed with an inert gas. In an embodiment, the packaging unit 100 is sealed inside an aluminum pouch having a low oxygen environment. The low oxygen environment inside the aluminum pouch may be generated by flushing the aluminum pouch with nitrogen or other functionally equivalent means. The low oxygen environment inside the pouch prevents any oxidative damage of the tissue 1 thereby enhances the shelf life of the tissue 1 without damaging the packaging unit 100.
[0069] The pouch containing the packaged tissue 1 within the packaging unit 100 may further be placed inside a box (or container). The box may be made of a material including but not limited to cardboard, fiberboard, paperboard, etc. The box may help in easy storage and/or handling.
[0070] Example 1 (Prior Art): A tissue is packaged in a packaging having a double barrier sealing. The double barrier sealing includes an inner packaging and an outer packaging. The tissue was placed within an inner tray of the inner packaging and sealed by a Tyvek lid. Further, the inner packaging was placed within an outer tray of the outer packaging and sealed by a Tyvek lid. The sealing of the Tyvek lids was done inside a blister packaging machine to make the double barrier seal.
[0071] However, during storage and handling, the tissue was in contact with Tyvek lid thereby compromising the properties of Tyvek lid and the tissue. Further, the shelf life of the tissue was drastically reduced due to the oxidative nature of the surrounding environment.
[0072] Example 2 (Present invention): A dehydrated tissue 1 was packaged in a packaging unit 100 of the present invention under a low-oxygen environment. First, the tissue 1 was placed within an inner cavity 111a of a PETG inner tray 111 and an aluminum sheet 113 with perforation 113a was placed over the tissue 1. The inner tray 111 of a primary packaging 110 was sealed with a Tyvek inner lid 115.
[0073] Thereafter, the primary packaging 110 was subjected to Ethylene oxide gas sterilization. During gas sterilization, the perforations 113a ensured even spread of the gas around the tissue 1 for efficient sterilization.
[0074] The primary packaging 110 was then placed over an inner step 131b of a PETG outer tray 131. Further, the outer tray 131 of a secondary packaging 130 was sealed with a Tyvek outer lid 133.
[0075] The packaging unit 100 was then sealed inside an aluminum pouch having a low oxygen environment. The low oxygen environment inside the aluminum pouch was generated by flushing the aluminum pouch with nitrogen. This low oxygen environment inside the aluminum pouch prevented any oxidative damage of the tissue 1 thereby enhances the shelf life of the tissue 1 without damaging the packaging unit 100. Further, the sheet 113 prevented absorption/seepage of any residual solvent/chemical present on the tissue 1 through the inner lid 115 thereby improving shelf-life of the tissue 1 without any change in tissue integrity.
[0076] The scope of the invention is only limited by the appended patent claims. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the teachings of the present invention is/are used.