Patent Application
20240197969
The present disclosure relates to medical procedures for the isolation, concentration and delivery of Alpha-2 Macroglobulin (α2M) molecules in an allogeneic or xenogeneic manner to treat musculoskeletal and/or respiratory conditions.
Medical study and research continues to reveal ever more detail about processes that occur in the bodies of human beings and other creatures, including details about the healing process that is triggered in response to injuries to a variety of tissues. By way of example, it has been found that injuries to at least musculoskeletal and respiratory tissues, whether caused by physical trauma, allergy response or disease, triggers a complex combination of both regenerative and destructive activities.
More specifically, there is a combination of growth of new tissue to repair and/or replace damaged tissue, and a remodeling of both old and new tissues to recreate the structure that was damaged with a correct shape and size. The remodeling process is effected by the provision of proteases at the location of the tissue damage to effectively “sculpt” the tissue structures that result from the growth process through the selective breakdown of the proteins making up portions of both old and new tissues. In effect, the healing process is meant to be a balance of both a growth process, and a selective destruction process in which excess portions of tissue are “trimmed” away.
Unfortunately, it is not uncommon for such “sculpting” to go too far as a result of an overabundance and/or hyperactivity of the proteases. The result may be misshapen tissue structures, the excessive formation of fibrotic tissue (e.g., scar tissue) in place of normal tissue, and/or the destruction of existing tissue that is not accompanied by replacement thereof.
In particular regarding musculoskeletal conditions, the result may be misshapen musculoskeletal structures (e.g., misshapen portions of bones), the excessive formation of fibrotic tissue (e.g., scar tissue) in place of normal musculoskeletal structures, and/or the destruction of existing musculoskeletal structures without repair (e.g., partial or complete loss of cartilage at a joint). By way of example, it may be that a physical injury to a joint triggers a misperformed healing process in which the proteases become overactive, thereby damaging the cartilage at the joint, and thereby triggering the onset of arthritis at the joint. The reduction in the cushioning provided by the cartilage may lead to inflammation at the joint, which can repeatedly re-trigger the same misperformed healing process. Over time, this may cause the destruction and loss of all cartilage at the joint, and a misshapening of portions of the bones at the joint.
In particular regarding respiratory conditions, the result may be misshapen air sac structures (e.g., enlarged and floppy air sac structures that are less effective), the excessive formation of fibrotic tissue (e.g., thickened air sac tissue), and/or the destruction of air sac tissue without repair (e.g., a reduction in the overall quantity of air sacs). By way of example, it may be that the inhalation of airborne allergens (e.g., fungi in a dusty feeding trough for horses), and/or particles having a microscopically sharp geometry that causes irritation (e.g., asbestos particles) triggers the inflammation of lung tissue, leading to a misperformed healing process in which the proteases become overactive. This may lead to thickening of air sac tissue that reduces the efficiency of blood oxygenation, and/or that causes the lungs to become less elastic such that physical act of breathing in and out requires more physical exertion.
Further, regarding respiratory conditions, for reasons that have remained unclear, rates of occurrence of various respiratory conditions, including asthma and obstructive pulmonary disease, have been observed to be increasing in recent years for a wide variety of creatures, including in various pets and farm animals (e.g., camels, dogs, horses, pigs, etc.). By way of example, in horses, rates of equine asthma (EA), including recurrent airway obstruction (RAO) and summer pasture-associated obstructive pulmonary disease (SPAOPD), have been observed to be increasing over the last couple of decades. These increasing rates also seem to mirror similar increasing rates of respiratory conditions in humans over a similar period of time.
Where humans are concerned, the increasing rates of respiratory conditions have already prompted increased efforts to discern the causes, and to develop treatments and/or cures. This has already resulted in an increasing variety of treatments available both over the counter and by prescription. A number of these treatments involve the delivery of a saline solution, and/or a solution of a pharmaceutical, in aerosolized form (e.g., through the use of a nebulizer). However, and regardless of the exact choice of delivery mechanism, many of such treatments are based on the use steroids that can have a variety of undesirable side effects.
Where horses are concerned, these increasing rates of occurrence of respiratory conditions such as EA have prompted a consensus in the veterinary community that there is now a pressing need for a similar increase in efforts to discern the causes, and to develop treatments and/or cures. Given the numerous biological similarities between humans and horses, and given the apparent similarities in increases in rates of respiratory conditions over a similar time period for both, a tendency has developed for treatments that were originally created for respiratory conditions in humans to be applied (at least experimentally) to treating respiratory conditions in horses. Unfortunately, this has also created at least the risk of having a similar variety of undesirable side effects in horses, such as those presented by the use of steroids.
An approach is needed to control the healing process for at least musculoskeletal and respiratory tissues to cause the healing process to proceed, as it should, with a better balance between the growth of new respiratory tissues and the “sculpting” of both old and new respiratory tissues.
Technologies are described for more efficiently isolating α2M molecules in a non-laboratory setting for use in treating musculoskeletal conditions.
A method for treating a medical condition of a patient with Alpha-2 Macroglobulin (α2M) molecules in an allogeneic or xenogeneic manner includes: drawing whole blood from a donor; separating plasma containing α2M molecules from other components of the whole blood; isolating the α2M molecules from the other components of the plasma; and administering at least some of the isolated α2M molecules to the patient via injection or inhalation, wherein the donor and the patient are different individuals.
A kit for treating a respiratory condition of a patient with Alpha-2 Macroglobulin (α2M) molecules in an allogeneic or xenogeneic manner includes at least one separator tube, wherein each separator tube of the at least one separator tube includes: an elongate transparent tube that defines an opening at one end that is sealed with a cap that is penetrable to receive whole blood drawn from a donor; and an amount of separator gel disposed within the separator tube to cooperate with a first centrifugal force exerted on the separator tube for a first period of time during a first centrifuging stage to separate plasma containing α2M molecules from other components of the whole blood. The kit also includes at least one isolator, wherein each isolator of the at least one isolator includes: a filter; a first cylinder defined by a first cylindrical wall having a first end that is configured to be closable with a septum cap that is penetrable to receive the plasma containing the α2M molecules following the first centrifuging stage, and having a second end that is closed with the filter; and a second cylinder defined by a second cylindrical wall having a first end that is closed where the second cylindrical wall narrows to form a conically-shaped end portion, and having a second end that defines an opening that is configured to be coupled to the filter in a manner that causes a first interior space of the first cylinder and a second interior space of the second cylinder to be separated by the filter, wherein the filter is configured to cooperate with a second centrifugal force exerted on the isolator for a second period of time during a second centrifuging stage to isolate the α2M molecules from other components of the plasma in preparation for administering the isolated α2M molecules to the patient. The kit further includes a transfer device, including a separator tube port configured to receive each separator tube of the at least one separator tube, one at a time, wherein the separator tube port comprises at least one hollow needle configured to penetrate the cap of each separator tube to couple the separator tube to a syringe port of the transfer device, and a syringe port configured to receive an end connector of a transfer syringe that is configured to be coupled to a transfer needle, wherein, following the first centrifuging stage and prior to the second centrifuging stage: while each separator tube of the at least one separator tube is coupled to the separator tube port, a plunger of the transfer syringe is operable to withdraw at least some of the plasma from within the separator tube and into the transfer syringe through the transfer device; and following transfer of plasma from each separator tube of the at least one separator tube, and with the transfer needle coupled to the end connector to penetrate the septum cap of each isolator of the at least one isolator, the plunger of the transfer syringe is operable to inject the plasma within the transfer syringe into the at least one isolator.
The disclosure will be better understood and when consideration is given to the drawings and the detailed description which follows. Such description makes reference to the annexed drawings wherein:
In the following detailed description, reference is made to the accompanying drawings that form a part hereof. In the drawings, similar symbols typically identify similar components, unless context dictates otherwise. The illustrative embodiments described in the detailed description, drawings, and claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented herein. It will be readily understood that the aspects of the present disclosure, as generally described herein, and illustrated in the Figures, can be arranged, substituted, combined, separated, and designed in a wide variety of different configurations, all of which are explicitly contemplated herein.
Broadly speaking, disclosed herein is a system and a method for isolating and concentrating α2M molecules from whole blood, and then administering those α2M molecules to a patient to treat either a musculoskeletal or respiratory condition. More specifically, the isolating and concentration of α2M molecules may entail the use of a centrifuge together with a set of separator tubes to perform centrifugation, followed by the use of one or more bags of plasma from the centrifugation with a peristaltic pump to isolate and concentrate the α2M molecules. The administration of the isolated and concentrated α2M molecules may entail the preparation and use of a syringe to inject those α2M molecules into a musculoskeletal structure in an allogeneic or xenogeneic manner, or may entail the preparation and use of a solution of those α2M molecules with the nebulizer in an allogeneic or xenogeneic manner.
A method for treating a medical condition of a patient with Alpha-2 Macroglobulin (α2M) molecules in an allogeneic or xenogeneic manner includes: drawing whole blood from a donor; separating plasma containing α2M molecules from other components of the whole blood; isolating the α2M molecules from the other components of the plasma; and administering at least some of the isolated α2M molecules to the patient via injection or inhalation, wherein the donor and the patient are different individuals.
A kit for treating a respiratory condition of a patient with Alpha-2 Macroglobulin (α2M) molecules in an allogeneic or xenogeneic manner includes at least one separator tube, wherein each separator tube of the at least one separator tube includes: an elongate transparent tube that defines an opening at one end that is sealed with a cap that is penetrable to receive whole blood drawn from a donor; and an amount of separator gel disposed within the separator tube to cooperate with a first centrifugal force exerted on the separator tube for a first period of time during a first centrifuging stage to separate plasma containing α2M molecules from other components of the whole blood. The kit also includes at least one isolator, wherein each isolator of the at least one isolator includes: a filter; a first cylinder defined by a first cylindrical wall having a first end that is configured to be closable with a septum cap that is penetrable to receive the plasma containing the α2M molecules following the first centrifuging stage, and having a second end that is closed with the filter; and a second cylinder defined by a second cylindrical wall having a first end that is closed where the second cylindrical wall narrows to form a conically-shaped end portion, and having a second end that defines an opening that is configured to be coupled to the filter in a manner that causes a first interior space of the first cylinder and a second interior space of the second cylinder to be separated by the filter, wherein the filter is configured to cooperate with a second centrifugal force exerted on the isolator for a second period of time during a second centrifuging stage to isolate the α2M molecules from other components of the plasma in preparation for administering the isolated α2M molecules to the patient. The kit further includes a transfer device, including a separator tube port configured to receive each separator tube of the at least one separator tube, one at a time, wherein the separator tube port comprises at least one hollow needle configured to penetrate the cap of each separator tube to couple the separator tube to a syringe port of the transfer device, and a syringe port configured to receive an end connector of a transfer syringe that is configured to be coupled to a transfer needle, wherein, following the first centrifuging stage and prior to the second centrifuging stage: while each separator tube of the at least one separator tube is coupled to the separator tube port, a plunger of the transfer syringe is operable to withdraw at least some of the plasma from within the separator tube and into the transfer syringe through the transfer device; and following transfer of plasma from each separator tube of the at least one separator tube, and with the transfer needle coupled to the end connector to penetrate the septum cap of each isolator of the at least one isolator, the plunger of the transfer syringe is operable to inject the plasma within the transfer syringe into the at least one isolator.
It has been found that α2M molecules, a component of blood in a great many creatures (e.g., camels, dogs, horses, humans and pigs) may be used in an autologous manner to treat such areas of damaged tissue to prevent such misperformances of the healing process. More specifically, it has been found that a concentrated dose of α2M molecules from a patient's own blood may be isolated and concentrated, and then introduced into damaged musculoskeletal or respiratory tissues of that patient by injection to prevent such hyperactivity of proteases at that location, and thus promote effective healing thereat.
Apart from such autologous use of α2M molecules (which is the subject of some of the aforementioned earlier applications) experimental work by the inventors in the present application has revealed that α2M molecules may be used in an allogeneic or xenogeneic manner to treat the same variety of conditions involving tissue damage and protease overactivity. In particular, it has been found that α2M molecules collected from one individual serving as a donor of a species (e.g., a human being or other type of creature) may be injected, in concentrated form, into a joint of another individual of the same species to successfully treat damage to the musculoskeletal structures of that joint, including damage arising from the onset of arthritis. It has also been found that α2M molecules collected from one individual of a species may be provided, in concentrated form and via a nebulizer, to another individual of the same species to successfully treat various respiratory conditions in that other individual, including various types of equine asthma (EA).
Medical research and testing are ongoing to explore and better understand the possible compatibility limitations of such use of α2M molecules in an allogeneic or xenogeneic manner. More specifically, the degree to which α2M molecules are transplantable between different individuals of either the same or different species is currently still uncertain. For example, of particular concern in allogeneic use is compatibility among blood types in some species. As is widely known, among human beings, there are just four blood types, of which type O negative is the one blood type that is deemed to be “universal” such that type O negative blood may be transfused into individuals of any of the other three blood types.
However, while there are many aspects of biology and medicine that may be relatively transferrable among different species, aspects of blood type has not proven to be one of them. For example, in a marked contrast to four types for human beings, among horses, it is estimated that there may be as many as 400,000 blood types. Over time, various criteria have been developed for identifying a subset of equine blood types that are able to be deemed to “universal” to a sufficient degree that blood from horses of that subset may be transfused to other horses with at least a greatly reduced likelihood of causing an adverse reaction. However, with so many blood types, it is usually the case that most transfusions of blood between two horses represents a first instance of a transfer of blood between two horses having their two particular blood types.
This situation concerning horse blood types has served to hamper efforts to determine whether there is such a thing as one or more truly universal blood types. As a result, concerns remain over whether it is possible for blood or blood components from one horse fitting the current criteria for being of a “universal” blood type are able to be repeatedly provided to another horse over a relatively lengthy period of time without that other horse developing a adverse immune response to the further provision of blood or blood components from that very same one horse.
In response to such issues as may exist in horses and/or other species, and in addition to the use of appropriate criteria for identifying donors having a universal blood type, a system and method of tagging and tracking may be implemented together with a system and method for isolating, concentrating and administering α2M molecules from the donors in an allogeneic or xenogeneic manner. Based on the ongoing medical research and experimental work for each species, a set of rules may be developed for distinguishing between combinations of donors and patients that are deemed to be safe for the transfer of α2M molecules therebetween, and combinations of donors and patients that are deemed to be unsafe for such a transfer.
Turning to
Thus, within each enrichment system 1000, 2000 or 3000, various techniques are employed to separate α2M molecules 17 from other components of that whole blood 11, to concentrate the α2M molecules 17, and to provide the concentrated α2M molecules 17 as multiple aliquots in separate ones of a set of multiple vials 800. From each such vial 800 in such a set, one or more α2M syringes 900 and/or a nebulizer of the inhalation system 4000 may be used in administering the α2M molecules 17 derived from the whole blood 11 to the patient 90. As also depicted, it may be that the patient 90 and the α2M vials 800 are provided with identifier tags 5090 and 5800, respectively, of the tracking system 5000 to enable tracking of at least patients 90 and the α2M vials 800 from which the α2M molecules 17 may be administered thereto.
Thus, as depicted, one or more whole blood syringes 100 may be used to draw whole blood 11 from a donor 10 that may be selected from among multiple donors 10, and to provide the whole blood 11 as an input to one of the enrichment systems 1000, 2000 or 3000. It should be noted that it may be envisioned that the whole blood 11 of multiple donors 10 is to never be combined, mixed or otherwise aggregated. Similarly, it may be envisioned that the α2M molecules 17 of multiple donors 10 are also to never be combined, mixed or otherwise aggregated. Within each enrichment system 1000, 2000 or 3000, various techniques are employed to separate α2M molecules 17 from other components of that whole blood 11, to concentrate the α2M molecules 17, and to provide the concentrated α2M molecules 17 as multiple aliquots in separate ones of a set of multiple vials 800. From each such vial 800 in such a set, one or more α2M syringes 900 may be used in administering the α2M molecules 17 derived from the whole blood 11 of a single donor 10 to at least one patient 90. Such administration may be via injection using the α2M syringe(s) 900, directly, or via inhalation using a nebulizer 4900.
As also depicted, it may be that one or more of the donors 10, the α2M vials 800 and the patients 90 are provided with one or more identifier tags 5010, 5800 and 5090, respectively, to enable tracking of the identities of the donors 10 and the patients 90. Such tracking may be used, along with a set of rules derived from research and observations of immune responses, to identify and distinguish between safe combinations of donors 10 and patients 90 between which α2M molecules 17 may be safely transferred, and unsafe combinations of donors 10 and patients 90 where the risk of an adverse immune response is deemed to be unacceptably high.
As is about to become apparent, the enrichment system 1000, unlike the enrichment systems 2000 and 3000 that are about to be described, entails the use of relatively small, lightweight and inexpensive components and devices. In particular, unlike the enrichment systems 2000 and 3000 that are about to be described, the enrichment system 1000 does not include a peristaltic pump. Thus, as will be appreciated by those skilled in the art, it is significantly more feasible to bring the components and devices of the enrichment system 1000 on a house call to a farm or other location at which larger animals may be kept, and away from a medical facility. Additionally, the enrichment system 1000 enables the isolation and concentration of α2M molecules 17 from the whole blood 11 of a donor 10 in less time than is possible using either of the enrichment systems 2000 or 3000.
The enrichment system 1000 is depicted and described in greater detail in
Thus, in a manner similar to the enrichment system 1000 of
Following the separation of the plasma from the other blood components, and in a manner similar to the enrichment system 2000 of
While the enrichment system 1000 may be capable of isolating and concentrating α2M molecules 17 from the whole blood 11 of a donor 10 in less time than is possible using either of the enrichment systems 2000 or 3000, the use of a peristaltic pump is more amenable to being scaled up to provide a greater volume of α2M molecules 17 from each donor 10. The enrichment system 3000 is depicted and described in greater detail in
Turning to
In embodiments of the enrichment system 1000 that include the set of vacuum separator tubes 1200b, each of the vacuum separator tubes 1200b may be a VACUTAINER® tube of a type offered by Becton, Dickson and Company of Franklin Lakes, New Jersey, USA. As will be familiar to those skilled in the art, each such vacuum separator tube 1200b, in its new and unused condition, may be pre-provided with a vacuum therein that the seal provided by the cap 1210 is used to maintain.
Regardless of which of the separator tubes 1200a or 1200b are used, the quantity of separator tubes 1200a or 1200b that are used may vary based on such factors as the volume of whole blood 11 that may be safely drawn from the donor 10, and/or the maximum quantity of separator tubes 1200a or 1200b that may be used with the centrifuge 1500 at a time. As those skilled in the art will readily recognize, the volume of whole blood 11 that may be safely drawn from a donor 10 may depend on at least the species of the donor 10, which again, may include and not be limited to, a camel, a dog, a horse, a human, a pig, etc. Thus, in embodiments of the system 6000 that incorporate the enrichment system 1000, it is contemplated that the system 6000 may be offered in differently-sized variants of kits, such as a smaller variant of kit that may include 1 to 4 separator tubes 1200a or 1200b, a mid-sized variant of kit that may include 5 to 8 separator tubes 1200a or 1200b, and/or a larger variant of kit that may include 9 to 16 (or still more) separator tubes 1200a or 1200b.
A plunger 110 of the whole blood syringe 100 may be operated to draw whole blood 11 from a blood vessel of a donor 10 (whether a human being or other type of creature) and into the whole blood syringe 100 via a needle 101 thereof. The whole blood syringe 100 may include a human-readable scale by which the volume of whole blood that is drawn is able to be measured as the plunger 110 is so operated to ensure that just the amount of whole blood 11 that is needed for the chosen quantity of separator tubes 1200a or 1200b is successfully drawn. After the appropriate volume of whole blood 11 is drawn, the whole blood syringe 100 may then be used to inject a portion of the drawn whole blood 11 into each of the separator tubes 1200a or 1200b through the cap 1210 via the needle 101.
As additionally depicted, in some embodiments, and prior to being used to draw whole blood 11 from a donor 10, the whole blood syringe 100 may be partially pre-filled (e.g., by the nurse, medical technician, veterinarian technician, doctor, veterinarian, etc.) with an amount of an anticoagulent 150, such as a citrate dextrose solution (ACD-A), to prevent the drawn whole blood from coagulating therein.
As also additionally depicted, each of the separator tubes 1200a or 1200b may carry an identifier (ID) tag 5200 that is indicative of identity of the donor 10 to associate the whole blood 11 therein with the individual from which it was drawn. In some embodiments, it may be that the ID tags 5200 are stickers that carry a one-dimensional or two-dimensional bar code that is associated with the donor 10. It may be that such stickers are printed on or about the time that the whole blood 11 is drawn from the donor 10 as part of a procedure that is meant to ensure that each of those particular ID tags 5200 does indeed carry a bar code indicative of the identity of that particular donor 10, and that the set of separator tubes 1200a or 1200b to which those particular ID tags 5200 are applied are indeed caused to contain the whole blood 11 of that particular donor 10. In other embodiments, it may be that the ID tags 5200 are radio frequency identification (RFID) tags that store data serving as an identifier of the donor 10. It may be that such an identifier is caused to be stored within such RFID tags on or about the time that the whole blood 11 is drawn from the donor 10 as part of a procedure that is meant to ensure that each of those particular RFID tags does indeed store an identifier associated with that particular donor 10, and that the set of separator tubes 1200a or 1200b that carry those particular RFID tags is indeed caused to contain the whole blood 11 of that particular donor 10.
Turning to
With the set of separator tubes 1200a or 1200b so filled with portions of whole blood 11, the set of separator tubes 1200a or 1200b may be placed within the centrifuge 1500 to be subjected to centrifugal force for a first period of time that is deemed sufficient to fully separate the plasma 13 thereof from the red and white blood cells 12 thereof. More specifically, and as depicted, the centrifuge 1500 may be used in conjunction with the separator gel 1250 to effect such a separation of components of the whole blood 11. Thus, when such isolation of the plasma 13 is complete, the separator gel 1250 within each of the separator tubes 1200a or 1200b should occupy a position that physically separates the plasma 13 from the red and white blood cells 12, thereby preventing these blood components 12 and 13 from becoming mixed together, again.
As depicted, and as will be familiar to those skilled in the art, the centrifuge 1500 may include a rotor 1552 that defines a set of holding positions 1520 that each have a shape and dimensions selected to hold a tube of matching shape and dimensions, such as one of the separator tubes 1200a or 1200b. As also depicted, it may be that the quantity and placement of such holding positions 1520, as defined by the rotor 1552, may be selected to enable various quantities of such tubes to be distributed among the holding positions 1520 in a manner that distributes the weight thereof in a balanced manner that enables relatively smooth operation of the centrifuge 1500.
As will also be familiar to those skilled in the art, it may be that the depicted rotor 1552 is exchangeable with one or more other rotors to thereby enable the centrifuge 1500 to be reconfigured to work with various different quantities and/or combinations of various tubes and/or other varieties of containers of differing shapes and/or sizes. Alternatively or additionally, it may be that the centrifuge 1500 is fitted with (or otherwise includes) a rotor with 2 or more “buckets.” Each such bucket may be able to be fitted with any of a variety of differing types of holder that may each be designed to provide holding position(s) for a differing quantity of and/or combination of various tubes and/or other varieties of containers of differing shapes and/or sizes.
Turning to
Each of the different types of transfer device 1300a, 1300b and 1300c may incorporate at least the depicted combination of a separator tube port 1320 and a syringe port 1340. Each of the different types of transfer device 1300b and 1300c may additionally incorporate a filtered air port 1330. As is about to be described, each of the different types of transfer device 1300a, 1300b and 1300c is configured to enable plasma 13 to be transferred from a separator tube 1200a or 1200b coupled to the separator tube port 1320, and to a transfer syringe 1400 coupled to the syringe port 1340. Additionally, and as is also about to be described, each of the different types of transfer device 1300b and 1300c is additionally configured to also enable external air surrounding the transfer device 1300b or 1300c to be drawn in through an air filter 1350 at the filtered air port 1330, and conveyed to the separator tube 1200a or 1200b that coupled to the separator tube port 1320.
It is envisioned that the interior volume of the transfer syringe 1400 is sufficiently large that all of the sum total of the amounts of the plasma 13 isolated within all of the separator tubes 1200a or 1200b (as a result of being subjected to centrifugal force by the centrifuge 1500, as earlier described) is able to be combined and retained within the transfer syringe 1400. As a result, it is envisioned that the transfer syringe 1400 is to remain connected to the syringe port 1340 by its end connector 1410 throughout the time that the plasma 13 is being transferred from each of the separator tubes 1200a or 1200b, and into the transfer syringe 1400.
As depicted, with a separator tube 1200a or 1200b coupled to the separator tube port 1320 such that the plasma needle 1321 penetrates the cap 1210 thereof, and with the end connector 1410 of the transfer syringe 1400 coupled to the syringe port 1340, there may be an initial equalization of pressures thereamong. However, it has been discovered by that the operation of the single-flow transfer device 1300a is not significantly changed by whether non-vacuum separator tubes 1200a or vacuum separator tubes 1200b are coupled to the separator tube port 1320. Thus, regardless of which type of separator tube 1200a or 1200b is coupled to the separator tube port 1320, pulling the plunger 1440 of the transfer syringe 1400 in a direction away from the end connector 1410 thereof may draw plasma 13 from within the separator tube 1200a or 1200b, and into the transfer syringe 1440, via the plasma needle 1321 and the end connector 1410.
As depicted, with a separator tube 1200a or 1200b coupled to the separator tube port 1320 such that the needles 1321 and 1329 penetrate the cap 1210 thereof, and with the end connector 1410 of the transfer syringe 1400 coupled to the syringe port 1340, there may be an initial equalization of pressures thereamong. More specifically, and especially where a vacuum separator tube 1200b is coupled to the separator tube port 1320, external air 99 may be drawn into the dual-flow device 1300a through the air filter 1350 of the filtered air port 1330, and then the resulting filtered air 93 may be conveyed into a separator tube 1200a or 1200b at the separator tube port 1320 via the air needle 1329. Pulling the plunger 1440 of the transfer syringe 1400 in a direction away from the end connector 1410 thereof may then draw plasma 13 from within the separator tube 1200a or 1200b, and into the transfer syringe 1440, via the plasma needle 1321 and the end connector 1410. In turn, more filtered air 93 may be drawn into the separator tube 1200a or 1200b to replace the plasma 13 that is so drawn out.
The three-way valve 1300c may incorporate a manually-operable valve (not specifically shown) of a type that is operable between at least two positions, where each position of the at least two positions causes one of the three ports 1320, 1330 or 1340 to be closed off from the other two of these two ports, while allowing gases and/or liquids to flow freely between the other two.
As depicted, for each separator tube 1200a or 1200b that is connected to the separator tube port 1320, the transfer of plasma 13 therefrom, and into the transfer syringe 1400, may begin with the three-way valve 1300b being operated to close off the separator tube port 1320, thereby connecting the syringe port 1340 to the filtered air port 1330. With the separator tube port 1320 so closed off, the plunger 1440 of the transfer syringe 1400 may be operated to draw filtered air 93 into the transfer syringe 1400. More precisely, the plunger 1440 of the transfer syringe 1400 may be operated to cause external air 99 that surrounds the three-way valve 1300b to be drawn in through the air filter 1350, thereby being filtered to become the filtered air 93 that is drawn into the transfer syringe 1400.
With an amount of such filtered air 93 now within the transfer syringe 1400, the three-way valve 1300b may then operated to close off the filtered air port 1330, thereby connecting the syringe port 1340 to the separator tube port 1320. With the filtered air port 1330 so closed off, the plunger 1440 of the transfer syringe 1400 may be operated to send filtered air 93 out of the transfer syringe 1400, through the three-way valve 1300b, through the plasma needle 1321, and into the separator tube 1200a or 1200b that is coupled to the separator tube port 1320. With filtered air 993 so conveyed into the separator tube 1200a or 1200b, the plunger 1440 of the transfer syringe 1400 may then be operated to draw most, if not all, of the plasma 13 out of the separator tube 1200a or 1200b, through the plasma needle 1321, through the three-way valve 1300b, and into transfer syringe 1400.
Referring back to each of
Turning
Turning to
One end of the first cylinder 1601 may be sealed (or sealable) with a septum cap 1610 that may provide a self-sealing aperture through which a needle or other form of tube of relatively small diameter tube may be inserted to effect the transfer of gases and/or liquids into and/or out of the interior volume of the first cylinder 1601. The other end of the first cylinder 1601 may incorporate a membrane filter 1650. In some embodiments, the membrane filter 1650 may have a molecular weight cutoff ranging from 100 kD to 500 kD.
The second cylinder 1602 may be configured to make the isolator 1600 more amenable for use with the centrifuge 1500. More specifically, one end of the second cylinder 1602 may be closed off with a conical end to ease insertion into the centrifuge 1500, while the other end may be open to enable the two cylinders 1601 and 1602 to be assembled by inserting part of the end of the first cylinder 1601 that includes the membrane filter 1650 therein.
It should be noted (and as depicted) that, in some embodiments, the isolator 1600 may be of an extended length variant 1600a in which the volume of the first cylinder 1601 is increased by sealing the end opposite the membrane filter 1650 with an extended variant of the septum cap 1610 that provides a cylindrical extension 1611 to the cylindrical wall of the first cylinder 1601 to increase the length of the first cylinder 1601. Alternatively, in other embodiments, the isolator 1600 may be of a standard length variant 1600b in which the volume of the first cylinder 1601 is not so increased. More precisely, instead of sealing the end opposite the membrane filter 1650 with the extended variant of the septum cap 1610, a standard variant of the septum cap 1610 is used in the standard length variant 1600b that does not provide the cylindrical extension 1611 of the extended length variant 1600a.
As additionally depicted, the isolator 1600 may carry an ID tag 5600 that is indicative of identity of the donor 10. In a manner similar to the ID tags 5200, it may be that the ID tag 5600, regardless of the technology it is based upon, may be printed and/or caused to store an identifier at a time on or about the time that the whole blood 11 is drawn from the donor 10. In this way, like the ID tags 5200, the ID tag 5600 is caused to store an indication of the identity of the individual from which the whole blood 11 is drawn.
Turning to
Turning to
In a manner similar to what was discussed in reference to
It should be noted that, although a variant of the rotor 1556 that provides a pair of the holding positions 1560 is depicted and described herein, other embodiments are possible in which the rotor 1556 may have more or fewer of such holding positions 1560. Further, to address situations in which the centrifuge is to be operated with a variant of the rotor 1556 that includes a quantity of holding positions 1560 that differ from the quantity of isolators 1600 that are to be inserted therein, one or more dummy weights of a shape, size and/or weight similar to an isolator 1600 may be used to enable balancing of the centrifuge 1500. Alternatively, an extra isolator 1600 filled with water may be used to serve such a purpose.
As will also be familiar to those skilled in the art, it may be that the depicted rotor 1556 is exchangeable with one or more other rotors (e.g., the rotor 1552 of
It should be noted that such use of the isolator 1600 with the centrifuge 1500 to perform the separation of the α2M molecules 17 from the rest of the plasma 13 originally transferred into the first cylinder 1601 has been found to provide a simpler approach than a peristaltic pump. The centrifuge 1500 is also a far simpler and far less expensive piece of equipment than a peristaltic pump. As a result, the enrichment system 1000 may be more suitable for being carried by and/or installed within a vehicle used to make house calls.
Turning to
It is envisioned that the amount of the α2M molecules 17 that are isolated from the whole blood 11 originally drawn from the donor 10 will be more than enough to fill more than one of the vials 800. In some embodiments, it may be deemed desirable to provide an amount within each of the vials 800 that is large enough to support multiple administrations of a dose, or of multiple doses, to the patient 90 (e.g., multiple administrations over the course of one or more hours). However, in other embodiments, it may be deemed desirable to provide an amount within each of the vials 800 that is small enough to support just a single dose or single administration of a dose to the patient 90, thereby enabling each dose or administration of a dose to be kept frozen in a separate vial 800 until the time comes that it is needed. Thus, it is envisioned that each aliquot is to be sized to enable one of the aliquots to be used to deliver a first amount to the patient 90, while one or more other aliquots may remain stored in a freezer to be preserved for the later instances of delivery to the same patient 90. In this way, the provision of multiple administrations and/or doses over the course of multiple days, weeks, months, etc. may be more easily supported.
As additionally depicted, each of the vials 800 may carry an ID tag 5800 that is indicative of identity of the donor 10. In a manner similar to the ID tags 5200 and 5600, it may be that the ID tags 5800, regardless of the technology on which they are based, may be printed and/or caused to store an identifier at a time on or about the time that the whole blood 11 is drawn from the donor 10.
Turning to
Turning to
The α2M reservoir 2600 may be a bag formed of flexible material, and may incorporate multiple ports by which needles of syringes may be connected thereto to inject fluids into the α2M reservoir 2600 and/or withdraw fluids therefrom. Such ports may also enable ends of various flexible tubes to be connected to the α2M reservoir 2600 to enable flows of gas and/or liquid into and/or out the α2M reservoir 2600. More specifically, the α2M reservoir 2600 may incorporate a filling port 2640 through which the transfer syringe 1400 may provide the plasma 13, as just described, and an extraction port 2670 from which α2M molecules 17 may later be extracted, as will be described.
Turning to
As will be familiar to those skilled in the art, the peristaltic pump 2500 may incorporate a rotary component (not specifically shown) that carries multiple rollers configured to repeatedly squeeze a flexible tube in a manner that moves along a portion of its length to thereby cause a flow of fluid therealong. An advantage of the peristaltic pump 2500 is that the fluid is caused too flow in a manner in which it is never directly exposed to any component of the peristaltic pump 2500, thereby simplifying efforts to maintain sanitary and non-contaminant conditions for the fluid. In this way, the need to clean components of the peristaltic pump 2500, itself, due to direct contact with the fluid is entirely obviated, as is the need to manufacture components of the peristaltic pump 2500 from materials specifically chosen to not chemically interact with and/or otherwise contaminate the fluid. Peristaltic pumps have long been favored for use in pumping blood and/or other bodily fluids for at least these reasons.
Thus, a portion of the output tube 2563 extending from the output port 2630 of the α2M reservoir 2600, and to the portion of the filter module 2300 that includes the cross-flow filter 2356, may be inserted into the portion of the peristaltic pump 2500 that incorporates such a rotary component to cause the output tube 2563 to be used in pumping the plasma 13 from the α2M reservoir 2600, and to the cross-flow filter 2356.
As will be familiar to those skilled in the art, the cross-flow filter 2356 may be physically shaped and/or otherwise configured to direct a flow of fluid in a tangential direction relative to the face of its filter media such that the flow of fluid essentially flows cross-wise relative to a face of its filter media. In some embodiments, it may be that the filter media of the cross-flow filter 2356 is selected to prevent molecules larger in weight than 500 kDa from passing therethrough.
With the output tube 2563 inserted into a portion of the peristaltic pump 2500, and with the peristaltic pump 2500 operated to cause a flow of the plasma 13 out of the α2M reservoir 2600 and toward the cross-flow filter 2356, the plasma 13 from the α2M reservoir 2600 may be caused to flow tangentially across the face of the filter media of the cross-flow filter 2356. As a result, molecules of the plasma 13 that are small enough to permeate through the filter media of the cross-flow filter 2356 are allowed to do so, and are caused by the pressure of the pumping of the plasma 13 into the cross-flow filter 2356 to leave the cross-flow filter 2356 via a permeate tube 2364, and to be deposited within a waste bag 2400 via a permeate port 2460 thereof. At the same time, components of the plasma 13 that do not permeate the filter media of the cross-flow filter 2356 are caused by the same pressure to leave the cross-flow filter 2356 via the retentate tube 2366, and to be returned to the α2M reservoir 2600 via the retentate port 2660 thereof.
Like the α2M reservoir 2600, the waste bag 2400 may also be formed of flexible material. The waste bag 2400 may also incorporate at least the aforementioned permeate port 2460 by which one end of the permeate tube 2364 may be connected thereto to enable at least a flow of gas and/or liquid into the waste bag 2400.
In this manner, the plasma 13 within the α2M reservoir 2600 is able to be repeatedly circulated in a cross-wise manner relative to the filter media of the cross-flow filter 2356 until at least most, if not all, of the components of the plasma 13 that are able to permeate the filter media have done so. As a result, the α2M reservoir 2600 is caused to retain the α2M molecules 17, while other components of the plasma 13 are separated therefrom, and deposited within the waste bag 2400.
As also additionally depicted, the α2M reservoir 2600 may carry an identifier (ID) tag 5600 that is indicative of identity of the donor 10. Again, in some embodiments, it may be that the ID tag 5600 is a sticker that carries a one-dimensional or two-dimensional bar code that is associated with the donor 10. It may be that such a sticker is printed on or about the time that the whole blood 11 is drawn from the donor 10 as part of a procedure that is meant to ensure that the ID tag 5600 does indeed carry a bar code indicative of the identity of the donor 10, and that the α2M reservoir 2600 to which the ID tag 5600 is applied is indeed caused to contain the plasma 13 of that particular donor 10. In other embodiments, it may be that the ID tag 5600 is a radio frequency identification (RFID) tag that stores data serving as an identifier of the donor 10. It may be that such an identifier is caused to be stored within such an RFID tag on or about the time that the whole blood 11 is drawn from the donor 10 as part of a procedure that is meant to ensure that the RFID tag does indeed store an identifier associated with that particular donor 10, and that the α2M reservoir 2600 that carries the RFID tag is indeed caused to contain the plasma 13 of that particular donor 10.
Turning to
Again, as additionally depicted, each of the vials 800 may carry an ID tag 5800 that is indicative of identity of the donor 10. In a manner similar to the ID tag 5600, it may be that the ID tags 5800, regardless of the technology on which they are based, may be printed and/or caused to store an identifier at a time on or about when the whole blood 11 is drawn from the donor 10.
Turning to
One end of the medication cup 4901 may be closeable with a cap 4910. The other end of the medication cup 4901 may incorporate a nebulizing diffuser 4950. In various embodiments, the nebulizing diffuser 4950 may employ any of a variety of techniques to generate an aerosol of whatever liquid may be placed within the interior volume of the medication cup 4901 between the cap 4910 and the nebulizing diffuser 4950. Such techniques for aerosolizing such liquids, include, but are not limited to, heating, ultrasonic vibration, etc.
One end of the aerosol chamber 4902 may be closeable with a cap 4980 that may be configured to enable the connection of the end (or other portion) of the medication cup 4901 that incorporates the nebulizing diffuser 4950 thereto in a manner that allows aerosols generated by the nebulizing diffuser 4950 to enter the interior volume of the aerosol chamber 4902. The cap 4980 may additionally include one or more inhalation inlets 4981 that may incorporate one-way valves that enable the entry of surrounding air into the aerosol chamber 4902, while preventing (or at least restricting) the release of the aerosols generated by the nebulizing diffuser 4950 into the surrounding air. The other end of the aerosol chamber 4902 may be configured to be connected to the inhalation mask 4903 in a manner that allows relatively free passage of air and aerosols from within the aerosol chamber 4902 and into the inhalation mask 4903.
The inhalation mask 4903 may incorporate an opening configured to allow the muzzle or snout of such a creature as a camel or a horse (i.e., where the patient 90 is such a creature) to enter into the interior space thereof, and may be further configured for connection to the aerosol chamber 4902 to receive air and aerosols therefrom. There may be still another opening formed in the inhalation mask 4903 that may be closeable with a cap 4990 that may additionally include one or more exhalation outlets 4991 that may incorporate one-way valves that enable the release of gases exhaled from the nose and/or mouth of the muzzle or snout of the patient 90 into the surrounding air, while preventing (or at least restricting) the entry of the surrounding air directly into the inhalation mask 4903. In this way, when then patient 90 inhales while wearing the inhalation mask 4903, the inhaled air is forced to pass through the aerosol chamber 4902, thereby enabling an aerosol generated by the nebulizing diffuser 4950 to be drawn into the inhalation mask 4903 along with the inhaled air.
Turning to
More specifically, and referring back to either of
Alternatively, and as also depicted in
It is envisioned that the amount of the α2M molecules 17 that are isolated from the whole blood 11 will be more than enough to support multiple instances of administering α2M molecules 17 to the patient 90 via inhalation. Thus, it is envisioned that at least one vial 800 will be filled with an aliquot of the α2M molecules 17 that is not meant to be used immediately in an administration of α2M molecules 17 to the patient 90.
Experiments conducted so far by the inventors in treating horses for EA have shown considerable effectiveness with 6 doses delivered at a rate of 1 dose every other day. As will shortly be explained, in these experiments, each dose is diluted with an equal volume of either 0.9% saline solution or lactated Ringer's solution. In these studies, all other medications and/or treatments for EA (if any) were discontinued for all horses. The results were promising, with most of the horses showing improvement. One horse experienced a transient episode of increased coughing associated with one instance of nebulization, and no horses demonstrated epistaxis. Subsequently, many of the horses demonstrated a decrease in clinical signs of EA for a period of 1 to 6 months, and while not being provided with any other medications. Several of the horses that began the study with more severe cases of EA have been able to be maintained with a single nebulization once every 4 weeks. A small number of these horses have additionally been provided with intermittent doses of medications to treat specific clinical signs associated with EA.
It should be noted that further experiments are planned by Applicant to attempt to derive more optimal parameters for the delivery of treatment, including and not limited to, the quantity of α2M molecules 17 to be delivered overall and/or for each aliquot, the number of doses (aliquots) to be delivered and/or their frequency, the ratio of mixture with saline solution and/or another form of dilution liquid, etc.
Turning to
Turning to
As the patient 90 exhales, the valves within the inhalation inlets 4981 and/or within the exhalation outlets 4991 cooperate with the pressure behind the exhalation by the patient 90 to stop the flow of air 99 and α2M solution aerosol 519 into the inhalation mask 4903 from the aerosol chamber 4902, thereby allowing another amount of the α2M solution aerosol 519 to collect within the aerosol chamber 4902 in preparation for the next inhalation by the patient 90. The valves within the inhalation inlets 4981 and/or the exhalation outlets 4991 also cooperate with the pressure behind the exhalation by the patient 90 to cause the exhaled gases from the patient 90 to be released from within the inhalation mask 4903 through the exhalation outlets 4991.
At 7110, a quantity of separator tubes may be prepared with separator gel deposited within each, and with each carrying an ID tag that carries an identifier of a donor (e.g., the separator tubes 1200, each with separator gel 1250 therein, and each carrying an ID tag 5200 with an identifier of one of multiple donors 10). At 7112, a quantity of aliquot vials may be prepared with each carrying an ID tag that carries the identifier of the donor (e.g., the aliquot vials 800, each carrying an ID tag 5800).
At 7120, one or more whole blood syringes may be used to draw whole blood from the donor (e.g., the one or more whole blood syringes 100 used to draw whole blood 11 from the one multiple donors 10), and to transfer that whole blood to the separator tubes.
At 7130, the separator tubes may be placed within a centrifuge (e.g., the centrifuge 1500), and the centrifuge may be operated to exert centrifugal force on the separator tubes. In this way, a combination of the exerted centrifugal force and the separator gel within each separator tube may be used to separate the plasma containing α2M molecules from other components of the whole blood (e.g., separating the plasma 13 from the red and white blood cells 12).
At 7140, a transfer device may be used to transfer the plasma from within each of the separator tubes to one or more transfer syringes (e.g., one of the transfer devices 1300a, 1300b or 1300c, to one or more of the transfer syringes 1400). At 7242, the one or more transfer syringes may be used to transfer the plasma into an α2M reservoir (e.g., the α2M reservoir 2600).
At 7150, the α2M reservoir may be connected to a filtration module and a waste bag (e.g., the filtration module 2300 and the waste bag 2400), and a peristaltic pump may then be used to circulate the plasma among the α2M reservoir, a cross-flow filter of the filter module and the waste bag (e.g., the peristaltic pump 2500). In this way, the plasma is repeatedly circulated through the filter module for a period of time sufficient to cause α2M molecules to remain within the α2M reservoir, while other components of the plasma pass through the cross-flow filter of the filter module, and into the waste bag.
At 7160, one or more α2M syringes may be used to transfer the α2M molecules from the α2M reservoir, and to the aliquot vials (e.g., the α2M syringes 1700 transferring α2M molecules 17 to the vials 800). With the α2M molecules so transferred to the aliquot vials, at 7162, the aliquot vials may be stored within a freezing environment (e.g., a freezer) to preserve the α2M molecules in storage for an extended period of time, or until needed to treat a patient.
Thus, at 7170, at a later time, an amount α2M molecules to administer to a patient in that dose may be determined. At 7172, a quantity of aliquot vials required to provide the dose to a patient may be retrieved from the freezing environment in which the aliquot vials were stored.
At 7174, the ID tag carried by each retrieved aliquot vial may be used to confirm that the α2M molecules stored therein are from a donor meeting the safety requirements for the patient. At 7176, each of such retrieved and confirmed aliquot vials may be thawed as part of preparing the α2M molecules stored therein for being administered to the patient.
If, at 7180, the thawed α2M molecules are to be administered by injection, then at 7182, one or more α2M syringes (e.g., the α2M syringes 900) may be used to so inject the patient with the thawed α2M molecules.
However, if, at 7180, the thawed α2M molecules are to be administered by inhalation, then at 7184, one or more α2M syringes may be used to transfer the thawed α2M molecules to a nebulizer (e.g., the nebulizer 4900). At 7186, the nebulizer may be used to administer those α2M molecules to the patient via inhalation.
At 7210, the amount of whole blood required to treat a respiratory condition of a patient (e.g., the patient 90—e.g., a camel, a dog, a horse, a human, a pig, etc.) may be determined. More precisely, a kit may be selected that includes sufficient quantities of separator tubes, isolators and aliquot vials to support the provision of enough α2M molecules to treat the patient from the whole blood of a donor (e.g., the α2M molecules 17 from the whole blood 11 of one of the multiple donors 10).
At 7212, the separator tubes may be prepared with separator gel deposited within each, and with each carrying an ID tag that carries an identifier of the patient (e.g., the separator tubes 1200, each with separator gel 1250 therein, and each carrying an ID tag 5200). At 7214, each isolator of the one or more isolators may be prepared with a filter carried within each, and with each carrying an ID tag that carries the identifier of the patient (e.g., the one or more isolators 1600, each with a filter 1650 therein, and each carrying an ID tag 5600). At 7216, the aliquot vials may be prepared with each carrying an ID tag that carries the identifier of the patient (e.g., the aliquot vials 800, each carrying an ID tag 5800).
At 7220, one or more whole blood syringes may be used to draw whole blood from the donor (e.g., the one or more whole blood syringes 100), and to transfer that whole blood to the separator tubes.
At 7230, the separator tubes may be placed within a centrifuge (e.g., the centrifuge 1500), and the centrifuge may be operated to exert centrifugal force on the separator tubes in a first stage of centrifuging (i.e., a first centrifugation) for a first period of time. In this way, a combination of the exerted centrifugal force and the separator gel within each separator tube may be used to separate the plasma containing α2M molecules from other components of the whole blood (e.g., separating the plasma 13 from the red and white blood cells 12).
At 7240, a transfer device may be used to transfer the plasma from within each of the separator tubes to one or more transfer syringes (e.g., one of the transfer devices 1300a, 1300b or 1300c, to one or more of the transfer syringes 1400). At 7242, the one or more transfer syringes may be used to transfer the plasma into one or more isolators.
At 7250, the one or more isolators may be placed within the centrifuge, and the centrifuge may be operated to exert centrifugal force on the isolator(s) in a second stage of centrifuging (i.e., a second centrifugation) for a second period of time. In this way, a combination of the exerted centrifugal force and the filter within each isolator that is filled with plasma may be used to isolate the α2M molecules from other components of the plasma. Again, where just one isolator is filled with plasma, a counterbalancing weight, or other isolator that is filled with water or another substance to serve as a counterbalancing weight, may be required to balance the centrifuge.
If, at 7260, the patient is to receive a dose of the α2M molecules, immediately, then at 7262, one or more α2M syringes may be used to transfer most of the α2M molecules from the isolator(s), and to the aliquot vials (e.g., the α2M syringes 1700 transferring α2M molecules 17 to the vials 800). However, some remaining amount of the α2M molecules may be retained within an α2M syringe for use in providing immediate treatment to the patient. With the α2M molecules so transferred to the aliquot vials, at 7264, the aliquot vials may be stored within a freezing environment (e.g., a freezer) to preserve the α2M molecules therein in storage for an extended period of time. With the most the α2M molecules so frozen, the immediate administration of α2M molecules to the patient may be performed, starting at 7290.
However, if, at 7260, the patient is not to receive a dose of the α2M molecules, immediately, then at 7270, one or more α2M syringes may be used to transfer all of the α2M molecules from the isolator(s). With the α2M molecules so transferred to the aliquot vials, at 7272, the aliquot vials may be stored within a freezing environment. With the most the α2M molecules so frozen, preparations for an administration of α2M molecules to the patient may begin at a later time, starting at 7280.
Thus, at 7280, at a later time, an amount α2M molecules to administer to the patient in that dose may be determined. At 7282, a quantity of aliquot vials required to provide the dose to the patient may be retrieved from the freezing environment in which the aliquot vials were stored.
At 7284, the ID tag carried by each retrieved aliquot vial may be used to confirm that the α2M molecules stored therein are from a donor meeting the safety requirements for the patient. At 7286, each of such retrieved and confirmed aliquot vials may be thawed as part of preparing the α2M molecules stored therein for being administered to the patient.
If, at 7290, the thawed α2M molecules are to be administered by injection, then at 7292, one or more α2M syringes (e.g., the α2M syringes 900) may be used to so inject the patient with the thawed α2M molecules.
However, if, at 7290, the thawed α2M molecules are to be administered by inhalation, then at 7294, one or more α2M syringes may be used to transfer the thawed α2M molecules to a nebulizer (e.g., the nebulizer 4900). At 7296, the nebulizer may be used to administer those α2M molecules to the patient via inhalation.
There is thus disclosed a system and a method for isolating and concentrating α2M molecules from whole blood, and then administering those α2M molecules to a patient to treat either a musculoskeletal or respiratory condition.
A method for treating a medical condition of a patient with Alpha-2 Macroglobulin (α2M) molecules in an allogeneic or xenogeneic manner includes: drawing whole blood from a donor; separating plasma containing α2M molecules from other components of the whole blood; isolating the α2M molecules from the other components of the plasma; and administering at least some of the isolated α2M molecules to the patient via injection or inhalation, wherein the donor and the patient are different individuals.
The medical condition may include at least one of: a musculoskeletal condition entailing damage to musculoskeletal tissue of the patient; or a respiratory condition entail damage to tissue of a respiratory tract of the patient.
The donor and the patient may be of the same species.
The donor and the patient may be of different species.
Drawing the whole blood from the donor may include: using a whole blood syringe comprising a hollow needle to draw the whole blood from the donor; and partially pre-filling the whole blood syringe with an anticoagulant before using the whole blood syringe to draw the whole blood from the donor.
The anticoagulant may include a citrate dextrose solution (ACD-A).
Separating the plasma from other components of the whole blood may include: depositing the whole blood into at least one separator tube, wherein each separator tube of the at least one separator tube contains an amount of separator gel; and subjecting the at least one separator tube to a first centrifugal force in a first centrifuging stage for a first predetermined period of time to cause a combination of the first centrifugal force and the separator gel within each separator tube of the at least one separator tube to separate the plasma of the whole blood within the at least one separator tube from red blood cells and white blood cells of the whole blood within the at least one separator tube.
Each separator tube of the at least one separator tube may include a vacuum separator tube that is pre-provided with a vacuum therein when in an unused condition.
Subjecting the at least one separator tube to the first centrifugal force in the first centrifuging stage may include placing the at least one separator tube within a first holder of a centrifuge; and the first holder may include either a first removable holder configured to be inserted into a bucket of the centrifuge, or a first exchangeable rotor of the centrifuge
Isolating the α2M molecules from the other components of the plasma may include: following the first centrifuging stage, transferring the plasma from the at least one separator tube and into at least one isolator, wherein each isolator of the at least one isolator comprises a filter; and subjecting the at least one isolator to a second centrifugal force in a second centrifuging stage for a second predetermined period of time to cause a combination of the second centrifugal force and the filter within each isolator of the at least one isolator to isolate the α2M molecules from the other components of the plasma within the at least one isolator.
Transferring the plasma from the at least one separator tube and into the at least one isolator may include: coupling a transfer syringe to a syringe port of a transfer device, wherein the syringe port is configured to receive an end connector of the transfer syringe that is configured to be coupled to a transfer needle; coupling each separator tube of the at least one separator tube, one at a time, to a separator tube port of the transfer device, wherein the separator tube port comprises at least one hollow needle configured to penetrate the cap of each separator tube to couple the separator tube to the syringe port of the transfer device; while each separator tube of the at least one separator tube is coupled to the separator tube port, operating a plunger of the transfer syringe to withdraw at least some of the plasma from within the separator tube and into the transfer syringe through the transfer device; and following transfer of plasma from each separator tube of the at least one separator tube, using the transfer syringe, with the transfer needle coupled to the end connector, to inject the plasma within the transfer syringe into the at least one isolator.
The filter of each isolator of the at least one isolator may have a molecular weight cut off ranging from 100 kD to 500 kD.
Isolating the α2M molecules from the other components of the plasma may include: following the first centrifuging stage, transferring the plasma from the at least one separator tube and into an α2M reservoir; and using a peristaltic pump to circulate the plasma among the α2M reservoir, a cross-flow filter and a waste bag to cause other components of the plasma to pass through the cross-flow filter and into the waste bag, while the α2M molecules remain within the α2M reservoir.
The cross-flow filter may be selected to prevent molecules of greater than 500 kDa from passing therethrough.
Administering at least some of the isolated α2M molecules to the patient via inhalation may include administering at least some of the isolated α2M molecules to the patient using a nebulizer.
The method may further include storing a remainder of the isolated α2M molecules within at least one vial in a freezing environment to preserve the remainder of the isolated α2M molecules for use in another administration of the isolated α2M molecules to the patient at a later time.
A kit for treating a respiratory condition of a patient with Alpha-2 Macroglobulin (α2M) molecules in an allogeneic or xenogeneic manner includes at least one separator tube, wherein each separator tube of the at least one separator tube includes: an elongate transparent tube that defines an opening at one end that is sealed with a cap that is penetrable to receive whole blood drawn from a donor; and an amount of separator gel disposed within the separator tube to cooperate with a first centrifugal force exerted on the separator tube for a first period of time during a first centrifuging stage to separate plasma containing α2M molecules from other components of the whole blood. The kit also includes at least one isolator, wherein each isolator of the at least one isolator includes: a filter; a first cylinder defined by a first cylindrical wall having a first end that is configured to be closable with a septum cap that is penetrable to receive the plasma containing the α2M molecules following the first centrifuging stage, and having a second end that is closed with the filter; and a second cylinder defined by a second cylindrical wall having a first end that is closed where the second cylindrical wall narrows to form a conically-shaped end portion, and having a second end that defines an opening that is configured to be coupled to the filter in a manner that causes a first interior space of the first cylinder and a second interior space of the second cylinder to be separated by the filter, wherein the filter is configured to cooperate with a second centrifugal force exerted on the isolator for a second period of time during a second centrifuging stage to isolate the α2M molecules from other components of the plasma in preparation for administering the isolated α2M molecules to the patient. The kit further includes a transfer device, including a separator tube port configured to receive each separator tube of the at least one separator tube, one at a time, wherein the separator tube port comprises at least one hollow needle configured to penetrate the cap of each separator tube to couple the separator tube to a syringe port of the transfer device, and a syringe port configured to receive an end connector of a transfer syringe that is configured to be coupled to a transfer needle, wherein, following the first centrifuging stage and prior to the second centrifuging stage: while each separator tube of the at least one separator tube is coupled to the separator tube port, a plunger of the transfer syringe is operable to withdraw at least some of the plasma from within the separator tube and into the transfer syringe through the transfer device; and following transfer of plasma from each separator tube of the at least one separator tube, and with the transfer needle coupled to the end connector to penetrate the septum cap of each isolator of the at least one isolator, the plunger of the transfer syringe is operable to inject the plasma within the transfer syringe into the at least one isolator.
Each isolator of the at least one isolator is may be configured to: receive the injection of the plasma within the first interior space within the first cylinder; and isolate the α2M molecules within the first interior space from the other components of the plasma within the second interior space.
The septum cap may further include a third cylindrical wall configured to serve as an extension to the first cylindrical wall to increase a volume of the first interior space when the first end of the first cylindrical wall is closed with the septum cap.
The kit may further include a nebulizer configured to be provided with the α2M molecules isolated during the second centrifuging stage, and to administer the α2M molecules to the patient via inhalation.
Various other components may be included and called upon for providing for aspects of the teachings herein. For example, additional materials, combinations of materials, and/or omission of materials may be used to provide for added embodiments that are within the scope of the teachings herein.
Standards for performance, selection of materials, functionality, and other discretionary aspects are to be determined by a user, designer, manufacturer, or other similarly interested party. Any standards expressed herein are merely illustrative and are not limiting of the teachings herein.
When introducing elements of the present disclosure or the embodiment(s) thereof, the articles “a,” “an,” and “the” are intended to mean that there are one or more of the elements. Similarly, the adjective “another,” when used to introduce an element, is intended to mean one or more elements. The terms “including” and “having” are intended to be inclusive such that there may be additional elements other than the listed elements.
While the disclosure has been described with reference to illustrative embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. In addition, many modifications will be appreciated by those skilled in the art to adapt a particular instrument, situation or material to the teachings of the invention without departing from the essential scope thereof. Therefore, it is intended that the claimed invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out this invention, but that the invention will include all embodiments falling within the scope of the appended claims.
This application is a continuation-in-part of U.S. patent application Ser. No. 18/535,841 entitled “SYSTEM AND METHOD FOR ISOLATION AND AUTOLOGOUS USE OF α2M MOLECULES TO TREAT RESPIRATORY CONDITIONS” filed Dec. 11, 2023 by Daniel J. Dreyfuss et al. (Attorney Docket No. JL1235.015); which is a continuation-in-part of U.S. patent application Ser. No. 18/215,498 entitled “SYSTEM AND METHOD FOR ISOLATING ALPHA 2M MOLECULES” filed Jun. 28, 2023 by David J. Lutz et al. (Attorney Docket No. JL1235.017); which is a continuation of U.S. patent application Ser. No. 17/837,090 entitled “SYSTEM AND METHOD FOR ISOLATING ALPHA 2M MOLECULES” filed Jun. 10, 2022 by David J. Lutz et al. (Attorney Docket No. JL1235.005); which claims the benefit of the priority date of U.S. Provisional Application 63/209,685 entitled “SYSTEM AND METHOD FOR ISOLATING α2M MOLECULES” filed Jun. 11, 2021 by David J. Lutz et al. (Attorney Docket No. JL1234.004); the disclosures of each of which are incorporated herein by reference for all purposes. This application also claims the benefit of the priority date of each of U.S. Provisional Application 63/467,497 entitled “SYSTEM AND METHOD FOR ISOLATING AND USE OF ALPHA 2M MOLECULES IN TREATING RESPIRATORY CONDITIONS” filed May 18, 2023 by Daniel J. Dreyfuss et al. (Attorney Docket No. JL1235.013); and of U.S. Provisional Application 63/541,116 entitled “SYSTEM AND METHOD FOR ISOLATION AND ALLOGENEIC USE OF α2M MOLECULES TO TREAT MEDICAL CONDITIONS” filed Sep. 28, 2023 by Daniel J. Dreyfuss et al. (Attorney Docket No. JL1235.014); the disclosures of each of which are also incorporated herein by reference for all purposes.
| Number | Date | Country | |
|---|---|---|---|
| 63209685 | Jun 2021 | US | |
| 63467497 | May 2023 | US | |
| 63541116 | Sep 2023 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 17837090 | Jun 2022 | US |
| Child | 18215498 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 18535841 | Dec 2023 | US |
| Child | 18424552 | US | |
| Parent | 18215498 | Jun 2023 | US |
| Child | 18535841 | US |
