Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
  • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
  • A61M1/3472—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
  • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
  • A61M1/342—Adding solutions to the blood, e.g. substitution solutions
  • A61M1/3424—Substitution fluid path
  • A61M1/3431—Substitution fluid path upstream of the filter
  • A61M1/3434—Substitution fluid path upstream of the filter with pre-dilution and post-dilution
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
  • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
  • A61M1/342—Adding solutions to the blood, e.g. substitution solutions
  • A61M1/3424—Substitution fluid path
  • A61M1/3437—Substitution fluid path downstream of the filter, e.g. post-dilution with filtrate
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
  • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
  • A61M1/342—Adding solutions to the blood, e.g. substitution solutions
  • A61M1/3455—Substitution fluids
  • A61M1/3458—Substitution fluids having electrolytes not present in the dialysate
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
  • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
  • A61M1/342—Adding solutions to the blood, e.g. substitution solutions
  • A61M1/3455—Substitution fluids
  • A61M1/3468—Substitution fluids using treated filtrate as substitution fluid
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
  • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
  • A61M1/3472—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate
  • A61M1/3486—Biological, chemical treatment, e.g. chemical precipitation; treatment by absorbents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
  • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
  • A61M1/3601—Extra-corporeal circuits in which the blood fluid passes more than once through the treatment unit
  • A61M1/3603—Extra-corporeal circuits in which the blood fluid passes more than once through the treatment unit in the same direction
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M2205/00—General characteristics of the apparatus
  • A61M2205/75—General characteristics of the apparatus with filters
  • A61M2205/7563—General characteristics of the apparatus with filters with means preventing clogging of filters
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M2206/00—Characteristics of a physical parameter; associated device therefor
  • A61M2206/10—Flow characteristics
  • A61M2206/16—Rotating swirling helical flow, e.g. by tangential inflows

Definitions

• This invention relates generally to an improved method fo filtering biological fluids including blood and, more specifically, to a method for filtering the blood of the kidney patient in order to remove accumulated waste components.
• the best known methods for removing waste materials from blood comprise various forms of dialysis.
• a portion of the blood water and low to moderate molecular weight waste materials diffuse through the membrane into the dialyzing fluid which must be continuously supplied in order to avoid electrolyte and toxin build-up which would stop or reduce the transfer of such materials from the blood.
• units based on this principle are widely available and fairly reliable, they have several disadvantages.
• the system as a whole is relatively complex and cannot be made readily portable.
• trained operator is required. Treatment typically involves a visit to the hospital or the like on the order of three times a week to remove the accumulated toxic waste build-up, adjust electrolytes in the body and remove any excess water.
• Treatment typically involves a visit to the hospital or the like on the order of three times a week to remove the accumulated toxic waste build-up, adjust electro
• efficient ultrafiltration is achieved by spiral geometry filter means with the blood flow parallel to the axis of the spiral an filtrate removal along the spiral in order to provide efficient blood filtration.
• the ultrafiltration method includes the use of a spiral filter and recirculation through the filter of a major fraction of the blood leaving the filter.
• Figure 1 shows the rejection characteristics of exemplary filters for use in this application.
• Figure 2 shows schematically a portion of a filter syste for removal, as an example, of middle molecular weight materi from a feed fluid.
• Figure 3 depicts important components of human blo including waste materials as a function of their molecular weig or cell size.
• Figure 4 shows the filtrate rate versus pressur characteristics of a filter suitable for removal of low an middle molecular weight materials from the blood.
• Figure 5 shows the clearance or removal rate versus th molecular weight of dissolved species as a function of th quantity of rejected materials (e.g. very high molecular weight proteins and/or cells) present on the filter membrane surface.
• rejected materials e.g. very high molecular weight proteins and/or cells
• Figure 6 is a schematic representation of an ultrafiltratio system suitable for blood and the like.
• Figure 7 is a plan view of a filter configuration suitable for use with the present invention.
• FIG. 8 illustrates the effect of recirculation through the convective feed path of the filter on its efficiency as a function of the blood composition and operating variables.
• the major fractions A and B spanning low and moderate molecular weights, include the electrolytes and at least a major portion of the toxins removed by the normal kidney.
• a third and fourth major fractions, C and D, of the blood have larger molecular weights and include proteins and antibodies.
• Fractions A, B, C and D together constitute the plasma portion of blood.
• the D fraction comprise molecular weights which range from approximately 45,000 to in excess of one million. Primarily platelets, red cells and white cells (the formed elements) exist in blood above the D fraction range .
• ultraf iltration has the potential to permit selective removal of undesired constituents without disturbing the rejected major fractions (Fraction D and the formed elements). For example, removal of the water/electrolyte/ toxin reactions (A and B) by filtration of blood through a membrane having a pore size
• Figures 1 and 2 Because most present filters have distribution of pore sizes, rejection may not occur precisely at and above a given particle size or molecular weight, but rathe increases over a limited range of particle sizes or molecula weights. To the extent that this range can be made to coincide with low concentration regions of the blood constituent spectrum, separation of the major blood constituents is possible. An intermediate component may be removed by the method depicted i
• the feed fluid i passed essentially normal to the plane of the filter.
• batch filtratio is feasible as a semi-continuous process because the water ca continue to flow through the sand which builds up on the upstrea side of the filter and filtration continues with only moderat increases in pressure.
• Batch filtration is not suitable fo continuous use with whole blood because the larger constituents effectively clog the filter and engender large pressure increase for a given filtrate rate. Filtration of blood can be made mor efficient and continuous"by the use of a convective filter wher the feed fluid flows approximately parallel to the filte membrane and thus tends to carry off those constituents of th fluid which decrease the filtrate rate.
• the clogging referred to herein can be two types ? surfa clogging and membrane pore clogging. Surfaceclogging is cause
• OMPI • / j .. IPO -* by rejected materials which accumulate on the surface (feed flui side) of the filter membrane The amount and density of thi type can be controlled by the methods, devices, and procedures described or referenced in this disclosure.
• the second type o clogging refers to constituents of the blood or other body fluid becoming immeshed within the membrane ultrastructure. This is, in general, less affected by convective events within the feed channel although there is still a possible mino contribution from events within the feed channel.
• the basic membrane filtration characteristics would be altered in the latter case wherein a different straight line buffered saline limit could be encountered (e.g. the straight line of Figure 4 would be rotated clockwise).
• Figure 4 shows how surface clogging affects the efficiency of filtration through its influence on the filtrate rate versus
• FIG. 6 shows schematically a preferred embodiment of this invention in the form of a kidney machine suitable for long term therapy.
• Input blood is extracted, as an example, from the patient's artery or internal fistula/shunt and passes to the input port 30 of the apparatus.
• the blood then passes to inpu port 3 of the convective ultrafilter 1.
• a pressure differentia TMP, across the filter membrane 9 causes water and wast components to separate from the blood circuit chamber 4 and pass through the membrane to the filtrate plenum 6.
• a portion of the filtrate withdrawn from the filter 1 may be discarded as indicated by W to withdraw excess water from the patient.
• the remainder of the filtrate is passed through a processor 11
• ⁇ COT ⁇ TUT ⁇ SHEET e.g. cartridges, secondary filters, etc. which removes waste materials (end products of metabolism, toxins) and adjusts the electrolyte concentration.
• the output of the processor 11 consists of water, electrolytes and nutrients at a rate F which is a fraction f of the input blood flow rate FF.
• This purified stream is returned to the patient and/or to the filter 1 as described in more detail hereinafter. That portion of the input blood which is not withdrawn as filtrate passes through and out of the convective filter at output port 5 of the filter and is returned to the patient's vein by way of apparatus output port
• Filter 11 preferably comprises a series of filters/cartridges each especially adapted to remove or change one or more of the plasma components. Suitable filters/cartridges are known to those skilled in the art and will not be described in detail here. Small quantities of makeup electrolytes, (such as calcium and magnesium), nutrients (such as glucose and/or amino acids) or medications (such as sodium bicarbonate, vitamins, etc.) may be added to the filtrate stream F which preferably also passes through a final bacterial filter before being returned to the patient; these details are not specifically shown in Figure 6.
• makeup electrolytes such as calcium and magnesium
• nutrients such as glucose and/or amino acids
• medications such as sodium bicarbonate, vitamins, etc.
• the convective filter 1 In order to achieve and maintain efficient ultrafiltration through filter 1, the convective filter 1 must be especially configured and operated using one or more forms of augmentation
• the input blood FF passes through th length L of the filter between the membrane elements 90.
• Elements 200 schematically represent a blood screen which serves to separate the membrane elements 90 by an appropriate distance, to introduce some resistance to flow into the blood path (whereb uniform flow is obtained) and to induce secondary flows which help keep the membrane clean.
• the model shown contains the membrane cast on a backing 400 sufficiently porous to allow easy flow of the filtrate towards the permeate collecting tube (500).
• Figure 6 is desirably on the order of 0.7 m for average adult intermittent application.
• the height H of the blood flow path is desirably in the range 0.25 to 1 mm? too small a value introduces excessive resistance into the blood flow path while too large a value results in inefficient filtration conditions and an impractically large filter.
• any impediments in the convective path do not appreciably reduce the effective width of the channel (i.e. active membrane) below its nominal value W.
• W effective width of the channel
• the filter consists of multiple hollow fiber membranes in a parallel arrangement, each with a bore diameter H, rapid plugging of a substantial number of the fibers can occur due to feed fluid concentration and the effective area is unacceptably diminished.
• W should be at least large as L.
• FIG. 7B and 7C there is shown a cross- section of a spiral filter.
• the membrane 9 ( Figure 6) comprises an envelope with the backing 400 from two opposing membranes elements 90 in contact 99 and glued together at the outer edges 66.
• the envelope and the blood screen 200 are both wound around central hollow mandrel 500 which serves as a conduit for th filtrate stream F.
• the porous backing 400 from envelope 9 open only onto holes 300 leading to the hollow portion of the mandrel
• the filtrate stream passes from the filter unit 1 throug the axis of the mandrel 500. Similarly, the blood passes throug the filter perpendicular to the drawing. More details of the construction of a spiral filter may be found in the Westmoreland
• the substrate materials have been described by Chevron Corp. Corp. and possibly polymethylmethacralate or other adhesive strategies common in the field.
• the substrate materials have been described by Roman numeral Corp. and possibly polymethylmethacralate or other adhesive strategies common in the field.
• the substrate materials have been described by Roman numeral Corp. and possibly polymethylmethacralate or other adhesive strategies common in the field.
• the substrate materials have been described by Roman numeral Corp. and possibly polymethylmethacralate or other adhesive strategies common in the field.
• the first type is an asymmetric cellulose acetate somewhat similar to the reverse osmosis membranes developed for desalinization.
• the exact annealing conditions will change with different cellulose acetate formulations and still produce an acceptabl membrane.
• the second type of membrane that can be used in hemofiltration is a modification of the newer, thin film composite reverse osmosis technology.
• the thin film composite reverse osmosis technology is, typically, a backing similar to the on
• the second modificatio of the thin film composite reverse osmosis technology would allo a thinner casting of the polysulfone base with an even thinne top film than is used in reverse osmosis.
• the criteria i easy passage of electrolytes and end products of metabolism wit insignificant passage of the larger plasma proteins. All of th modifications outlined above are easily accomplished by technical personnel well versed in membrane technology.
• the blood sid spacer 200 In order to achieve efficient hemof iltration, the blood sid spacer 200 must have certain characteristics. Many thick commercial screens will not work due to their ineffectiveness in
• Vexar made by DuPont (polyethelene), with 12 strands to the inch an measuring a total thickness of approximately 25 mils. (0.025 inches).
• the preferred orientation is to have the mesh lines at an approximate angle of 45° to the flow direction as shown in
• a preferred casting material to enclose the spiral filter and direct the blood and filtrate streams is polycarbonate or an equivalent biocompatible material.
• the same material has been used for the filtrate collection tube onto which the rolled spiral assembly is wound.
• the wound assembly is sufficiently smaller than the inside diameter of the polycarbonate housing, to enable potting of the wound assembly into the polycarbonate shell using medical grade silicone adhesive.
• Dimensions applicable to hemofiltration are a membrane width of 10 inches with a wound assembly diameter of 2 and 2/3 inches. This yields an effective membrane area considered to be a minimum for adult human intermittent application of 0.7 meters squared.
• Other details of construction are similar to existing spiral wound technology in the reverse osmosis field, with the exceptions of having to use biocompatible materials and avoiding turbulence in the blood flow path.
• a filter in accordance with the foregoing description will still not result in efficient hemof i ltrat ion unless it i operated as now described. It has been found essential for maintenance of efficiency to recirculate a large fraction of the blood exiting the filter at port 5 by reintroducing it a input port 3 at recirculation rate R times the input blood flo rate FF. R must be substantially larger than 2 with a nominal
• FF 200 to 250 cc/min.; values on the order of 3-8 are require to assure high efficiency with the filter membranes and device used hitherto and described hereinbefore. While there is a present no comprehensive and exact theoretical basis for th relation of the value of R to the filter parameters and bloo composition, most factors are known and at least two factors ar believed substantial.
• R the use of large amounts o recirculation R enhances the compositional homogeneity of th blood along the length of its flow path through the channel 4.
• typical blood input flow rate range is 200-250 cc/minute with typical filtrate rate of 80 cc/minute. Without recirculation, then, the plasma portion of the blood would be depleted o approximately half of its water by the time it reached output port 5.
• the filter input flow rate is in the range 1000-1250 cc/minute so that withdrawal of 80-100 cc/minute of water results in a much lower percentage change in blood composition down the length L of the filter.
• the increased rate of flow through the filter with recirculation is in the range 1000-1250 cc/minute so that withdrawal of 80-100 cc/minute of water results in a much lower percentage change in blood composition down the length L of the filter.
• Figure 8 gives data illustrative of the effect of th recirculation ratio R on the efficiency of the filter
• This efficiency relationship is further dependent on HCT, PH, TMP, and fibrinogen levels for a given filter design, i.e. H, W, L and screen design.
• the limit value for the efficiency ranges above 80% and depends inter alia on th variables indicated as well as other factors listed on Figure 8.
• Another method is to have the membrane supported by an irregula plastic insert with the transmembrane pressure sufficient t deform the membrane over the perturbation typically moded into the plastic support.
• An example of irregular but controlle channel geometries would include tight coiling of the feed channel, having periodic or asymmetric surface waviness paralle to the flow, and folding of the flow channel again in a manne to induce flow diversion in the direction of flow.
• the membrane can be constructed to contain fixed repellant charges.
• a tubular blood channel can benefit by using ribbon to produce spiral flow (secondary flows) in addition to axial flow through the tube. Examples of externally applie forces can include, but are not restricted to, the applicati of surface charge (in the absence of significant membrane charge electrically induced with the insertion of electrodes in eithe
• Ultrasound may be implemented in several ways, including crystals directly exposed to the feed channel. This is the most electrically efficient way of transmitting ultrasound frequency. It is also the least efficient in promoting filtration efficiency while posing the possibility of "heat" damage to the blood.
• a less electrically efficient way of producing ultrasound is to have the transducer face placed parallel to the direction of the feed flow, either in or underneath the membrane structure. Although less electrically efficient, the augmentation of filtration by the membrane is most effective with this orientation. Ultrasound reacts with any and all acoustic interfaces, one such important interface being the membrane/fluid junction.
• SUBSTITUTE SHEET Ultrasound techniques include the use of a single frequency, frequency spectra, and combination of frequencies dependen upon the application. Examples of physical movement include
• washing machine agitation, continuous rotation with speci rotating seals or connectors, or linear vibration, all applied t the entire filtering module.
• Staging of devices includes the use of more than one device arranged in a parallel and/or sequential manner. This allows direct introduction of cleanse filtrate into the feed flow between each module. This dilute the feed flow, allowing more efficient filtration in each module but normally at the price of increased total surface area (mor modules) with concomitant improvement in total clearance o effective filtration.
• Staging may also be of the macrostage variety, in which selected reintroduction of filtrate can be achieved by desig along an otherwise continuous flow channel. Staging is als meant to imply any method of intermittently "mixing up" the fee stream to eliminate any component polarization within the fee stream. Another variation of staging also found to be effectiv is the alternating of active and inactive filtering areas.
• independent control of biochemical and biophysical conditions includes the p H in the feed channel

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• Health & Medical Sciences (AREA)
• Heart & Thoracic Surgery (AREA)
• Life Sciences & Earth Sciences (AREA)
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• Biomedical Technology (AREA)
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• 1982
  • 1982-04-13 EP EP82901649A patent/EP0076320A1/de not_active Withdrawn
  • 1982-04-13 WO PCT/US1982/000449 patent/WO1982003567A1/en not_active Ceased
  • 1982-04-13 GB GB08235450A patent/GB2108400A/en not_active Withdrawn

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