|Title of Invention||
A SYSTEM AND A METHOD OF REMOVAL OF CONDENSED WATER FROM BLOOD BAG SYSTEM
|Abstract||A system having blood bag sealed within plastic cover, further enclosed,within a second protective cover, forming a very narrow annular space inbetween, having dehydrating agent in the said annular space, wherin the second protective outer cover is impervious and multilayered having atleast three layers, an inner polyethylene lalyer, an outer polyester layer and a central aluminium foil|
|Full Text||Field of Invention:
The invention relates to sterilization of medical products, more specifically blood bag system. The best way to sterilize medical products within collapsible plastic containers is to seal them within a permeable protective plastic outer cover and autoclave the system. This procedure ensures that the inner containers are sterile both inside and outside. Sterility of the outer surface is particularly desirable in the case of products such as blood bags, constant Ambulatory Peritoneal Dialysis bags, containers for umbilical cord blood and such other critical healthcare system as it guarantees that no transfer of microorganisms could take place from the outer surface of containers to the site of phlebotomy or other procedures. This process is covered by Indian Patent No. 179473 (1992).
A difficulty associated with the above mentioned sterilization procedure as known in the prior is the accumulation of some quantity of water in the space between the inner container and its protective outer cover. This water is derived from two sources: -
1. From the steam within the autoclave
2. From the anticoagulant solution within the inner container.
The actual contribution of moisture from the two sources mentioned above varies depending upon the thickness of the inner bag and its protective outer cover, the types of plastic materials used and the water vapour permeability of the types of sheets used. If the water vapour permeability of the outer protective cover is high, the contribution of moisture
from the autoclave to the total condensed water could be as high as 65 percent. This implies that the loss of moisture from the anticoagulant solution will be low which is a very desirable feature.
The removal of the condensed water from within the outer protective cover is covered by two Indian Patents as foUows:-
(1) Indian Patent No.l79474 (1992) and
(2) Indian Patent No.l79475 (1992)
The former Patent advocates the drying of the system after autoclaving, in chambers in the temperature range 40 to 70'oC. The removal of water is best done at the rate of 0.02 to 0.03 g/hour, which is achieved at around 60-65*^C. The second Patent advocates the removal of a good part of the air from the space between the inner container and its outer protective cover before the autoclaving operation, which results in the condensation of less quantity of water within the outer cover. Consequently, the time required for drying at 40-70°C is considerably reduced from 20-24 hours to 10-12 hours for 450 ml capacity single blood bags. The quantity of condensed water is higher for double, triple and quadruple bag systems - up to 0.70 g and consequently the drying time required is also higher. In a blood bag manufacturing facility working at high capacity, the drying operation would be crucial and would be the rate controlling operation.
Objects of the Invention:
The main invention is to achieve a method of manufacture of autoclavable plastic container ilood bags, wherein the water vapour permeability of the blood bags and outer cover are not unduly altered in drying chamber at elevated temperature, during the process for removal of water condensed within the space between blood bags and the protective covers after the process of sterhzation.
Brief Description of invention:
The blood bags or other plastic containers sealed within protective outer covers made of polymeric films after sterilization by autoclaving are freed of moisture adhering on the outer surface by mechanical means such as tilting or shaking if necessary, followed by a short period of drying in a heated chamber within air circulation. They are then placed within an impermeable outer cover/container where low humidity is maintained. The low humidity promotes the diffusion of moisture from within the protective cover to the outside. Maintaining a higher temperature in the chamber would increase the water vapour transmission rate of the protective outer cover and would help in reducing the period required for drying. However the temperature above TO'^C is counter productive because of the marked increase in permeability of the inner bag itself.
Description of drawings:
The blood bag system are further illustrated in figure-1 & 2,
Figl. Illustrates quadruple bags sealed in first set of plastic cover (1), sealed further within the second set of protective multilayered cover (2) alongwith the dehydrating agent sachet (3) placed within the interspace.
Fig2. Illustrates single bag sealed in first set of plastic cover (1), sealed further within the second set of protective multilayered cover (2) alongwith the dehydrating agent sachet (3) placed within the interspace
Description of the Invention:
The approach applicable to blood bags, constant ambulatory peritoneal dialysis bags and similar devices developed by us is as follows: -
Various procedures have been tried by us to reduce the quantity of water, which accumulated within the protective outer cover and for its easy removal. We have achieved good success when the permeability of the outer cover was increased by the use of more permeable materials. Outer covers based on cellulose materials, polyesters, nylon, non woven polyolefin's and multi-layered films based on one or more of the above materials have been found to make distinct improvements. When high permeable materials such as those mentioned above are used for outer cover, steam penetration into the outer cover is predominant and hence up to 65% of the water condensed is derived from this source. The contribution from the anticoagulant solution being much less, the change in concentration of anticoagulant chemicals is very small, which is a very desirable advantage. The drying time required in such case is significantly reduced by 20 to 50 per cent. Considerations such as cost and the availability of permeable films having the desired characteristics such as clarify strength, sterilisability with steam, resistance to abrasion, and sealability, limit the range of materials suitable for manufacturing operations.
After sterilization by autoclaving the blood bags or other devices sealed within protective outer covers are subjected to a tilting procedure to drain out water droplets on the surface. The autoclave trolleys in which the blood bags are positioned could be tilted to achieve the water removal.
The autoclave trolleys are then directly transferred into drying chambers where temperature is maintained at 80-90°C with air circulation inside. This operation would remove moisture on the surface of the protective outer covers. The time required for the drying step would be 1 to 2 hours at 80-90°C. This operation does not remove the condensed water within the outer covers significantly.
In the next step, the blood bags within their protective covers are immediately packed within impervious multi-layered covers having aluminium film as the central layer. The air within the outer cover is displaced with nitrogen or carbon dioxide. Sachets containing an appropriate quantity of a dehydrating agent are positioned within the cover, which is then sealed. The sachet of dehydrating agent helps to maintain a dry atmosphere around the outer cover of blood bags which promotes the transport of moisture from within the protective outer cover of blood bags to the outside and is ultimately absorbed and fixed by the dehydrating agent.
In this system, the water vapour permeability of the blood bag and outer cover are not unduly altered unlike what happens when the bags are kept in a drying chamber at elevated temperatures. Plasticized PVC has a high permeability to water vapour of around 8-18g per square meter per 24 hours whereas polypropylene film of 50 microns has permeability of around 4.0 - 6.0 g/m2/24h. At elevated temperatures, the permeabilities may increase several
times for the inner bag as well as for the outer cover. This can cause more moisture to come out of the inner bag from the anticoagulant than that which could go out through the polypropylene outer cover at temperatures more than 60oC. This could cause build up of moisture within the outer cover. When dry conditions are maintained around the outer cover at lower temperatures such as 20-30oC, there is no alteration in the relative permeability of the plastic films. However there is an increase in permeability of the protective outer cover because of the reduced humidity outside.
Many dehydrating agents could be used for the process described above. Silica gel, alumina gel, zeolites of various types and even organic polymers having high water absorbing characteristics have been found to be effective by us.
The preferred dehydrating agent should be a solid, should have high capacity for absorption of water, should not deliquesce to a sticky product, should not be susceptible to bacterial or fungal growth and should be sterilisable by heat. Silica gels, alumina gels, fused alums, fused aluminium sulphate and zeolites meet all these requirements. Costs and availability of the materials are also important considerations. Considering all these factors, silica gel with fine pore structure and surface area in the range 300-500 square meters per gram and capable of absorbing up to 40% of its weight of water was found to be the best option. The dehydrating agent should be packed within sachets made of highly permeable outer covers. Sachets made of woven/non-woven polyethylene; polyesters, nylon, rayon or other polymers have very desirable characteristics since they combine high permeability with high wet strength.
A very important consideration for the process to be successful is the quantity of the dehydrating agent to be used, which is meant to remove only the water condensed within the outer protective cover. Presence of excess dehydrating agent would cause the removal of moisture from the anticoagulant itself, which is not desirable. Under normal conditions of autoclaving when an outer cover of poly propylene of 60-65 micron thickness is used, the condensed water would be around 0.3 - 0.6 g for double bags (450 ml capacity main bag and 400 ml capacity satellite bags), and 0.6 - 0.7 g for triple and quadruple bags (main bag - 450 ml capacity and satellite bags of 400 ml capacity). The moisture removing capacity of the silica gel should be assessed and its quantity adjusted to remove only the quantities of condensed water as described earlier. The silica gel may be used as a single sachet or as multiple sachets. In the case of multiple bags, we find that it is advantageous to place more than one sachet within the impervious outer packing, whereas in the case of single blood bags use of one sachet is usually sufficient.
The success of the process depends upon the non-permeability to moisture of the final outer packaging. A multi layer outer pouch fabricated from polyethylene - aluminium foil polyester is fairly reliable in this regard provided that the aluminium foil is at least 8-12 microns thick. The inner layer may be made of multi-layered films consisting of one or more polyolefin's to give good strength to the package. The outer layer may be made of polyesters or nylon to provide strength and abrasion resistance. Impermeability to moisture is provided by the aluminium foil in the middle layer. Under the normal situation the following configuration has been found to be most suitable.
1. Polyethylene inner layer - 80-110 microns - consisting of one or more polyolefin layers
2. Aluminium foil -8-10 microns
3. Polyester nylon outer layer - 10-12 microns
Moisture removal from the protective outer cover of blood bags by the invented process is a rather slow process. The time required for the complete removal of the condensed water varies depending upon the type of blood bag being processed. Around 12 days would be required for 450 ml capacity single bags packed in an impervious outer cover. More time was needed for multiple bags - 12-13 days for triple bags, 13-20 days for triple bags -SAGM, and quadruple bags when stored at 30±2°C.
The rate of moisture removal is high during the first day and it gradually tapers off in succeeding days as the silica gel gets saturated with moisture. A storage period of up to 20 days after packaging ensures the complete removal of the condensed water within the protective cover of blood bags when the appropriate quantity of silica gel is used at storage temperature of 30±2°C.
The temperature of storage during the first 20 days is important.
We find that the optimum temperature range for storage of packaged blood bags is 30±2°C. At lower temperatures the time required for moisture removal is higher whereas at higher temperatures such as 40±2'oC there is risk of moisture loss from the anticoagulant also.
The use of silica gel, alumina gel, zeolites and other materials for the removal of moisture is well known. The novelty of the invented process resides in the use of a
predetermined quantity of dehydrating agent such as silica gel to selectively remove the water which condensed within the protective outer cover of blood bags during the process of steam sterilization. The dehydrating agent should get fully exhausted after this so that the water from the anticoagulant within the blood bag is not removed to any significant extent.
An important achievement of the invented process is the simplification of the blood bag manufacturing process. In the earlier process covered by Indian Patents 179473, 179474 & 179475, the blood bag systems could be packaged only after a prolonged drying operation of at least 10-15 hours. The invented process enables final packaging to be done within two hours after steam sterilization. The invented process reduces the period of exposure of sterilized blood bags to the atmosphere and thus minimizes the possibility of microbial and other contamination of the outer surface of the protective cover of blood bags.
The invented process thus consists of a process to remove the water which gets condensed in the annular space between the blood bags and/or other devices and their protective plastic cover by the use of a dehumidifying agent such as silica gel, alumina gel, fused aluminium sulphate and zeolites in the outermost water impermeable protective pack characterized in that the quality and quantity of the dehydrating agent as also the storage temperature are so adjusted as to remove only the condensed water within the space between the blood bag and/or devices and their protective outer cover.
We Claim :-
1. A system having blood bag sealed within a plastic cover, further enclosed within a
second protective cover, forming a very narrow annular space inbetween, having dehydrating agent in the said annular space, wherein the second protective outer cover is impervious and multilayered having atleast three layers, an inner polyethylene layer, an outer polyester layer and a central aluminium foil.
2. A blood bag system as claimed in claim 1, wherein the said outer cover has the inner layer 80-100 microns thick, the outer layer 10-12 microns thick and the central layer 8-10 microns thick.
3. A blood bag system as claimed in claim 1, wherein the said dehydrating agent include anyone of silica gel, aluminium gel, fused alums, fused aluminium sulphate and zeolites in solid form, the said dehydrating agent with pore structure and surface area in the range of 300-500 square meter per gram and capable of absorbing 40% of its weight of water, and said dehydrating agent enclosed within sachets, said sachet being woven or non woven polyethylene group member.
4. A blood bag system as claimed in claim 1, wherein the said plastic film for plastic
cover is so selected herein such that its relative permeability does not alter at 20-3 0°c temperature, and whereas the second plastic cover is so formed such that its relative permeability increases in reduced humidity of 20-30oc temperature.
5. A blood bag system as claimed in claim 1, wherein said sealing means the captured air within is displaced with nitrogen or carbon dioxide.
6. A blood bag system as claimed in claim 1 , wherein said blood bags mentioned therein include peritoneal dialysis bags and other similar medical devices adapted for air tight sealing system.
7. A method for making a sealed sterilized blood bag system comprising the steps of: sealing the blood bags in their protective first plastic cover to form a first assembly, autoclaving the first assembly,
- draining off the water droplets on the outer surface of the outer covers in the first assembly by tilting the autoclaving trolleys mechanically,
- sealing the first assembly within a second protective cover with dehydrate agent placed inbetween to form a second assembly,
drying the second assembly in drying chamber at 80-90°C with air circulation for a duration of 1-2 hours so as to remove the moisture on the outer surface of the second protective cover in second assembly, and
diffusing the moisture from within second protective cover to outside by keeping the second assembly in low humidity chamber at temperature less than 70oc for duration between 12-40 days.
8. A blood bag system and a method for making a sealed structured bag system as claimed in claim 1 & 7, as described in complete specification.
Dated this the 30th day of August 2004.
|Indian Patent Application Number||678/CHE/2003|
|PG Journal Number||34/2011|
|Date of Filing||26-Aug-2003|
|Name of Patentee||TERUMO PENPOL LIMITED|
|Applicant Address||IX/1323, SASTHAMANGALAM, TRIVANDRUM 695 010|
|PCT International Classification Number||A61J1/00|
|PCT International Application Number||N/A|
|PCT International Filing date|