JP2997099B2 - System for producing sterile aqueous solution - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

FIELD OF THE INVENTION The present invention relates to a method and system for producing purified water, sterile water or sterile aqueous solution for biological and medical applications. The present invention more particularly relates to a method and apparatus for producing a sterile aqueous solution that satisfies all user specifications, including bacteriological specifications, which allow for direct or indirect administration to a patient.

[0002]

BACKGROUND OF THE INVENTION Conventional water purification systems using well-known techniques such as reverse osmosis, deionization and ultrafiltration are capable of producing chemically and biologically pure water for short periods of time.
When operating continuously these systems, bacteria and pyrogens, the period the system is Ru is actuated, it is common to keep a low level. This period varies depending on the temperature at which the system is operated.
Wrong. During the operation of the system, biologically active substances such as bacteria, yeasts, molds, and pyrogens grow to unacceptably high levels in the system, producing the normally pure This leads to biological contamination of water. Some conventional systems restore the ability to produce biologically pure water by rinsing the system with a sanitizing agent such as formalin or chlorine to control biological contaminants. These sanitizers perform well, but are highly toxic to humans, difficult to handle and difficult to rinse out of the purification system. Moreover, the use of these chemicals, ring
It has a major not evil influence of Sakaikami. A second way to ensure the biological purity of the water treated with the membrane filter system is to treat the system with a second process that ensures control of the whole organism. One such method is to heat the water in a Pasteur sterilization process. However, components in the system, such as certain reverse osmosis membranes, cannot withstand Pasteur sterilization temperatures. Thus, when using a system sanitized with hot water, undesirable bypass loops and valves to the reverse osmosis membrane are introduced. Therefore, this method does not clean and sanitize the reverse osmosis unit. A third method is to pass purified water through a filter that can filter all biologically active substances from the water. However, this process requires that the initial filtration process reduce bacterial contamination to a sufficiently low level so that the bacteria removal filter does not prematurely block. This is a very expensive and infeasible plan. Thus, after initial filtration, chemical sanitizing agents are still needed to keep the bacterial levels in the system low.

[0003] Sterile urological lavage fluids (related to the urinary tract)
U.S. Pat. No. 3,300,035 to provide a composition used to wash or clean body parts) by continuously passing the composition through a filter designed to remove bacteria. No. 578,774. However, this device requires an on-site source of non-pyrogenic water and urological lavage fluid. Also, a reverse osmosis unit for removing pyrogens, a dissolved solids and a pyrogen may be used to produce a pyrogen-free, bacteria-free cleaning solution that can be administered directly to a patient. By using a combination of a deionization unit for removal and a filter for removal of bacteria, on-site production is disclosed in US Pat.
No. 3,457. However, while this system is claimed to remove pyrogens by deionization, it is limited to removing some pyrogens and is necessary to produce bacteria- and pyrogen-free water. It cannot be used to produce bacteria- and pyrogen-free water, as it is not all-removed. In addition, the system requires chemical sanitization and cleaning, thereby increasing the risk to the patient. U.S. Pat. No. 3,578,774 or 4,253
All of the means disclosed in US Pat. No. 457 produce water that meets the USP XXII standards for water for injection or flushing for a long period of time without the need for personnel to monitor, care and chemically sanitize the unit. Can not do. GB 1,450,030 and 2,034,584 also disclose means for providing pyrogen-free and bacterial-free aqueous solutions at the point of use of the solution. However, each of these systems heats the water used to form a chemical disinfectant such as formalin or an aqueous solution to sanitize the equipment, typically from 150 ° to 1 ° C.
Relies on using flash sterilization to reach a temperature of 60 ° C. The use of chemical sanitization, even if it is an effective means of killing microorganisms, is undesirable because it also introduces harmful chemicals into the system, which can be accidentally administered to patients. Moreover, heat sterilization of the water used to form the aqueous solution is undesirable because sterilization is only accomplished in some parts of the system that are exposed to high temperatures. Sterilization and pyrogens continue to grow in the rest of the system, thereby failing to achieve the desired liquid quality.

[0004] US Pat. No. 4,610,790 discloses a USP from tap water that includes a carbon-based filtration unit, a reverse osmosis unit, a deionization unit and an ultrafiltration unit.
A system for producing XX grade water is disclosed. The ultrafiltration unit and the deionization unit are flushed with heated water in order to disinfect the system of accumulated microorganisms and pyrogens. Flush the reverse osmosis unit with unheated water and periodically replace the carbon-based filtration unit. Since the carbon-based filtration and reverse osmosis units are not exposed to hot water, additional bypass loops and valves must be added to the system. Unsanitized filter units may eventually produce unacceptable quality products.
In addition, this system requires an extra filtration unit to remove bacteria and pyrogens since the reverse osmosis unit cannot be heat sanitized. Thus, the corner care and maintenance is a minimum, and automatically sanitizing system operation and monitoring
It would be desirable to provide a means for producing sterile water which eliminates chemical sanitization, bypass loops and extra filtration steps.

[0005]

According to the present invention, AA is used for dialysis standards.
A method and system for producing water quality satisfying MI water, USP XXII water for injection and sterile water for injection specifications. The portable water is passed through a pre-filtration stage, a carbon adsorption module and a reverse osmosis module to produce a water quality that meets AAMI water standards for dialysis. To produce a water quality that satisfies USP XXII water for injection, an ion exchange filtration step is added to the system, if necessary, to produce AAMI water from water containing undesirably high salt concentrations. To produce sterile water for injection, a disposable sterile microfilter is added as a final element to produce USP XXII grade water. The system can be used to produce solutions such as peritoneal dialysis fluids, intravenous infusions and other medical fluids. Liquid production is achieved by accurately metering the concentrated liquid into the high purity water produced by the system at a predetermined ratio. For example, US chloride for injection to concentrate (20 times concentration) for sodium chloride injection
PXXII grade water is mixed at 19 parts water to 1 part concentrate and then passed through a disposable sterile microfilter to produce a sterile sodium chloride injection solution. The final solution can either be filled into sterile intravenous (IV) containers or used directly for medical applications. Similarly, peritoneal dialysate can be made by adding concentrated peritoneal dialysate to the AAMI reference water generated by the system, and then passing the solution through a disposable sterile microfilter. The final solution can be filled into sterile containers or administered directly to the patient's peritoneal cavity. Microbiological growth control in all of the above systems includes pre-filters, carbon sorption modules, reverse osmosis modules, and ion exchange filtration modules, and includes all filters in the system except for periodically changing items such as disposable sterile microfilters. This is accomplished by circulating and / or flushing hot water periodically over a permanent wet surface for a predetermined period of time. If a semi-permanent sterile microfilter such as a ceramic microfilter is utilized, it can also be sanitized during the sanitization phase.

[0006] According to the description the present invention particular embodiment, injection USP XXII grade sterile water, generated by performing pre-filtering to portable water, carbon adsorption, reverse osmosis, deionization and finally sterile microfiltration Is done. The USP XXII standard for water injection, The United, dated January 1, 1990
States Pharmacopeia Conv
ention, Inc. XXII, 1456 and 14
This is described in detail on page 57. The specifications include tolerance limits for heavy metals and other chemical (organic and inorganic) contaminants, pH and total dissolved solids. Purified water must be sterile and non-pyrogenic. Chemical impurities in the portable water are removed by various filtration methods that have entered the system. The pre-filter element removes any particulate matter present in the water. The carbon filter element satisfies the dual requirement of removing halogens and dissolved organics present in the influent. Reverse osmosis elements remove dissolved ionic impurities, certain organisms, and also provide a barrier to bacteria and pyrogens present in the water. The deionization element removes traces of ionic impurities remaining in the purified water from the reverse osmosis module. Finally, the sterile microfilter provides a sterile barrier for any residual bacteria in the system.

To maintain control of the hygiene system, ie the bacterial population and pyrogen levels in the system, a new periodic, preferably daily, system sanitization method is used. Sanitization is by circulating or flushing hot water into the system for a combination of temperatures sufficient for sanitizing the system, but for a period of time less than the decomposition of the material in the module occurs. Achieved. For example, water at a temperature of about 80 ° -100 ° C. can be circulated through the system for up to 2 hours. The heated water is passed over all wet surfaces in the system, thereby limiting bacterial growth during operation and / or play of the system. Operation of the system, during play time, and pyrogens generated during the sanitization, excluding flushed in flush after sanitizing system. During operation, the reverse osmosis module remains a barrier for bacteria and pyrogens. At the end of the operating period (during sanitization), the heated water kills bacteria on the inlet side of the reverse osmosis module as well as bacteria that may have passed through the reverse osmosis module. After the heat-generating substance, it was sanitized
While flushing , flush out all sections of the system. The disposable sterile microfilter becomes a barrier for all bacteria in the system and is always used during operation, but is removed before sanitizing. The microfilter changes periodically and therefore does not need to be sanitized. Certain microfilters, such as ceramic microfilters, can be semi-permanent and can therefore be sanitized with other components. The ability of the system to produce sterile water for injection depends on a combination of three main modes of operation. They are as follows: (1) generation of sterile water for injection; (2) sanitization of the system and (3) flushing of the system. A typical mode of operation for operating the system involves producing sterile water for approximately 22 hours. The system is then sanitized with heated water such as 80 ° C. for 2 hours, after which the system is flushed with cold water for about 15 minutes. After flushing, the system is ready to produce sterile water again according to the method described above. During the water generation stage, the filter removes impurities from the incoming portable water as described above. The prefilter element, the carbon element and the deionization element retain their respective impurities and are discarded when capacity is exhausted. The reverse osmosis element is a tangential flow device consisting of three separate streams, feed, waste and product. Water from the feed side passes laterally across the surface of the semi-permeable membrane in the element (sweep) and is discarded via a waste stream. Part of the feed water passes through the membrane as purified water and is processed further if necessary.
Microbial impurities from the feedwater are retained and / or discarded via a waste stream.

Very small amounts of microbiological contaminants can pass through the reverse osmosis element and contaminate elements located downstream of the reverse osmosis element. These contaminants are then captured by a disposable sterile filter element located downstream. The system can produce sterile water by this means. It is a well-established fact that if bacteria are left uncontrolled in aqueous systems, they will grow and eventually produce water quality below the desired specification for microbiological contaminants. . To manage the bacteriological population in the system,
Develop innovative methods. The method involves controlling the entire system at a temperature and time to control the microbial population to the desired level as required by user requirements, e.g., about 80 on a daily basis.
It involves sanitizing at about 2 ° C or higher for about 2 hours. Circulating and / or flushing the heated water through the system reduces the growth of bacteria present in the inlet and outlet sides of the pre-filter element, carbon element, reverse osmosis element and associated piping and appendages in the fluid passage. prevent.
At the conclusion of the sanitization period, the system can be flushed to carry away destroyed bacteria and liquor production can begin again. By using this periodic heat sanitization, the biofilm formed in the system is inactivated because the heat of destruction penetrates the entire thickness of the formed biofilm. This is in contrast to chemical sanitization, which is usually less effective at controlling biofilms.

Referring to FIG. 1, the system used in the present invention includes a portable tap water inlet 10. The tap water is regulated by a valve (V1) 12 and a pressure regulator (PR) 14. A heat exchanger (HE) 16 is installed to collect waste heat from the system. Tap water is supplied by a pump (MI) 20. The supply flow rate to the reverse osmosis element is adjusted using the bypass valve (V2) 18. Tap water heater (H)
Towards 22, the system can be activated to maintain the desired temperature of the system. Water and then the pre-filter (P
F), and a differential pressure monitor (ΔP) 23 is set on the pre-filter 24. The differential pressure monitor 23 determines when the prefilter pressure difference exceeds a predetermined limit for replacing the filter. The water is then passed through an adsorption element (C) 26 containing a refractory ion exchange resin, activated carbon particles or a mixture thereof. The adsorbent particles used in step 26 can withstand the heat of water used to sanitize the system in a subsequent sanitization step. Differential pressure monitor (△
P) 25 may be used to determine when the pressure differential of an element exceeds a predetermined standard pressure for replacement. The filtered water is then passed through a reverse osmosis unit (RO) 28 containing a heat resistant membrane that can withstand the heat of the water used in the subsequent sanitization step. Conductivity monitor (C1), (C
2), 27 and 29 monitor the performance of the reverse osmosis unit (RO) 28. The conductivity monitor (C2) 29 also ensures the quality of the water produced. Reverse osmosis unit (R
O) The waste conduit from 28 passes through back pressure regulator V3 (33). Back pressure regulator V3 allows adjustment of the product to waste ratio. Valve (V4) 32 remains closed during operation and while sanitizing, reverse osmosis unit (RO) 28
To operate at a high sanitizing temperature, a minimum back pressure is desired, so it is left open. During normal operation, purified water can be passed through valve (V5) 30 and then used as dialysis water. The valve (V6) 34
It remains closed during normal operation. If the system is sanitized with water heated by a heater (H) 22, the water passes through a pre-filter (PF) 24, an adsorption unit (C) 26, a reverse osmosis unit (RO) 28 and then discarded The valve (V4) 32 on the product conduit side and the valve (V6) 34 on the product side, while the valve (V5) 3
0 remains closed during sanitization. The water from the waste conduit side and the valve (V6) 34 are combined at location 35 and passed to a wastewater channel 36 after heat is recovered through heat exchanger (HE) 16. The heater (H) 22 is then rendered inactive at the completion of sanitization and flushes the heated water from the system with incoming portable water. An air break or check valve (CV) 51 is placed in the drain to prevent contaminated water from flowing back into the product.

Referring to FIG. 2, the elements of FIG.
They are included in the diagram system and bear the same reference numbers. The system in FIG.
If necessary, the system can be produced from a water source containing an undesirably high salt concentration to produce a water quality equal to or better than the standard specified for USP XXII water for injection. An ion exchange module (IX) 37 is included. Conductivity monitors (C2) and (C3), 29 and 38 monitor the efficiency of the ion exchange module (IX) 37. The conductivity monitor (C3) 38 also ensures the quality of the water produced. When sanitizing the system with warm water, the heater (H) 22 is activated as the water passes through the reverse osmosis unit (RO) 28 as discussed in FIG. Water from the product side of the reverse osmosis unit (RO) 28 passes through an ion exchange module (IX) 37, then through a valve (V6) 34, and with the water from valve (V4) 32, and then into a heat exchanger. After passing through (HE) 16, it is discarded from waste water channel 36. Valve (V5) 30 remains closed during sanitization. The system is then flushed as described above. Referring to FIG. 3, the elements of FIG. 2 are included in the system of FIG. 3 and are numbered the same. The system of FIG. 3 includes a sterile microfilter (MF) 39, which is disposed of after a cycle that produces sterile water for injection. During the sanitization phase, heater (H) 22 is activated and hot water is circulated through modules 24, 26, 28 and 37 and then through 34 to 16 to wastewater channel 36. The system is then flushed with water to elute remaining pyrogens and directed to waste water channel 36.

Referring to FIG. 4, there is shown a system for producing a solution containing a drug, such as a peritoneal dialysis solution. The system shown in FIG. 4 is the same as the system shown in FIG. 1 except that a means for proportionally distributing purified water and a concentrated drug is provided. All other components function as described above. The concentrated peritoneal dialysis (drug) solution is stored in a container 44 and a proportioning module 46
And is mixed with purified water from a reverse osmosis unit (RO) 28. The proportioned solution is then used through a sterile microfilter (MF) 39. The sanitization of the system is the same as shown in FIG. 1, but if desired, the container (CN) 44 and associated piping are placed in a high temperature sanitization loop to maintain bacterial and pyrogen control. The system is then flushed as described above. Referring to FIG. 5, the elements of FIG. 4 functioning as described above are placed in the system and an ion exchange module (IX) 37 is added. The concentrated medical solution is in a container (C
N) 50, dispensed via the proportioning module 46 and placed in an admixture with purified water from the ion exchange module (IX) 37. The purified diluted medical solution is passed through a sterile microfilter 39 for use. The sanitization of the system is the same as shown in FIG. 2, but if desired, the container (CN) 50 and associated piping can be placed in a high temperature sanitization loop to maintain bacterial and pyrogen control. The system is then flushed as described above. It should be understood that the above description of the drawings illustrates preferred embodiments of the invention. The adsorption stage (C) 26 and the reverse osmosis stage (RO) 28 can be in any order. For example, if the incoming impure water does not contain chlorine or if the reverse osmosis membrane is resistant to chlorine, the reverse osmosis stage (RO) 28 can precede the adsorption stage (C) 26. However, when producing sterile products, a sterile microfilter (MF) 39 is always used downstream of the reverse osmosis and / or adsorption step.

[Brief description of the drawings]

FIG. 1 is a schematic diagram of the method and system of the present invention for producing water satisfying the standard value of AAMI standard water for dialysis.

FIG. 2 is a schematic diagram of the method and system of the present invention for producing water quality that meets USP XXII specifications for injection quality water.

FIG. 3. USP XXI for sterile water for injection quality water
1 is a schematic diagram of the method and system of the present invention, including a sterile microfilter, for producing water quality that meets I specifications.

FIG. 4 is a schematic diagram of the method and system of the present invention for producing a sterile peritoneal dialysis solution.

FIG. 5 is a schematic diagram of the method and system of the present invention for producing a sterile medical solution.

[Explanation of symbols]

 Reference Signs List 16 heat exchanger 22 heater 23 differential pressure monitor 24 prefilter 25 differential pressure monitor 26 adsorption element 27 conductivity monitor 28 reverse osmosis unit 29 conductivity monitor 37 ion exchange module 38 conductivity monitor 39 microfilter

──────────────────────────────────────────────────の Continuation of the front page (51) Int.Cl. ⁷ Identification code FI C02F 9/00 503 C02F 9/00 503B 504 504E (72) Inventor Ralph Kryel 330, Dartmouth Street, Boston, Mass., USA ) Surveyed field (Int.Cl. ⁷ , DB name) C02F 9/00 502-504

Claims (9)

(57) [Claims] 1. (a) filtration means adapted to remove particulate impurities from water; (b) adsorption means containing an adsorbent for removing chlorine and dissolved organic matter; (c) organic matter, dissolved solids min, microorganisms and pyrogens reverse osmosis separation means, adapted to remove from the water; means for passing (d) Portable water filtration means, the intake Chakushudan and reverse osmosis separation means;
And (e) filtering means heated water, periodically the suction Chakushudan and reverse osmosis means through, so the production of pure water from a portable water source comprising means for controlling microorganisms in the flash vital system the accumulated pyrogens system. 2. A deionization means adapted to remove dissolved solids from water, a reverse osmosis separation means, a means for passing water from the reverse osmosis means to the deionization means, and a means for periodically transferring heated water to the deionization means. 2. The system of claim 1 wherein the pyrogen accumulated through the system is flushed and located downstream of the means for controlling microorganisms in the system. 3. The system of claim 1, wherein a sterile microfiltration means adapted to remove bacteria from the water is located downstream of the reverse osmosis separation means. 4. A deionization means adapted to remove dissolved solids from water, a reverse osmosis separation means, a means for passing water from the reverse osmosis means to the deionization means, and a means for periodically transferring heated water to the deionization means. 4. The system of claim 3 wherein the pyrogen accumulated through the system is flushed and located downstream of the means for controlling the microorganisms in the system. 5. The system of claim 3 including means for proportioning the peritoneal water with the water exiting the reverse osmosis means and entering the sterile microfiltration means. 6. The system of claim 3 including means for proportioning the concentrated drug solution with water exiting the reverse osmosis means and entering the sterile microfiltration means. 7. Steps (a) and (b) in which portable water is successively used
And (c). 8. A portable water, successively filtering means, intake Chakushudan The system of claim 3 through the reverse osmosis separation means and sterile filtration means. 9. through reverse osmosis separation means initially the portable water, then any one of the system through to請 Motomeko 1-8 adsorption means.