Bicarbonate containing solutions for use during medical treatment are provided. The bicarbonate containing solution of the present invention includes at least two separate components including a bicarbonate concentrate and an electrolyte concentrate which can be readily and sterilely mixed to form a ready-to-use formulation for patient administration, particularly as applied to the treatment of acute renal failure associated with critically ill patients in an intensive care setting.

SUMMARY OF THE INVENTION

The present invention provides improved bicarbonate containing solutions that can be effectively administered during dialysis therapy, such as continuous renal replacement therapy. The bicarbonate containing solution of the present invention includes at least two separate components including a bicarbonate concentrate and an electrolyte concentrate which can be readily and sterilely mixed to form a ready-to-use formulation for patient administration, particularly as applied to treat acute renal failure associated with critically ill patients in an intensive care setting.

In an embodiment, a two part dialysis solution is provided. The two part dialysis solution at least includes a first component and a second component. The first component at least includes a bicarbonate concentrate and the second component at least includes an electrolyte concentrate. The first and second components can include a variety of other suitable constituents to ensure that the first and second components can be readily and sterilely mixed to form ready-to-use formulations.

For example, the first and second components, in an embodiment, each include physiological acceptable amounts of sodium, such as an amount of 160 mmol/L or less. In an embodiment, the first and second components each include physiological acceptable amounts of potassium, such as an amount that ranges from about 0.1 mmol/L to about 5 mmol/L. Alternatively, the first component which contains the bicarbonate concentrate does not include potassium where the second component does include potassium.

The ready-to-use formulations of the present invention can be prepared in a number of suitable ways. In an embodiment, the first and second components are separately stored from each other, such as in separate and hydraulically connected chambers of a multi-chamber container, until mixed together to form a mixed solution. In this regard, the ready-to-use formulation can be prepared within the container by mixing its two components within one chamber of the container. This can effectively eliminate the need to manually inject all or at least a portion of the components into the container to form the mixed solution, thus ensuring that the ready-to-use formulation can be readily prepared under sterile conditions.

Further, the container can be configured such that one of the components can be placed in direct fluid communication with the patient prior to mixing while the other component cannot be placed in direct fluid communication with the patient prior to mixing. This can provide an added level of safety with respect to the preparation and administration of the ready-to-use formulation of the present invention as the component that cannot be placed in direct fluid communication with the patient physically cannot be fed to the patient unless it is first mixed with the other component. In this regard, if, by chance, the component that physically cannot be placed in direct fluid communication with the patient were to have an undesirable concentration of constituents, such as potassium, sodium or the like, this configuration would necessarily ensure that the undesirable level of constituents is not fed or administered to the patient.

In another embodiment, the present invention provides a method of providing hemofiltration. The method includes the steps of providing a first component and a second components as previously discussed, mixing the first and second components to form a mixed solution and using the mixed solution during hemofiltration.

In an embodiment, the mixed solution is used as a dialysate. Alternatively, in an embodiment, the mixed solution is administered as an infusion solution during continuous renal replacement therapy.

An advantage of the present invention is to provide improved bicarbonate-based solutions.

Another advantage of the present invention is to provide improved bicarbonate containing solutions which include a number of components, such as an electrolyte concentrate and a bicarbonate concentrate, that can be readily and sterilely mixed to form a ready-to-use formulation suitable for administration to a patient during medical therapy including dialysis therapy.

Still another advantage of the present invention is to provide improved systems and methods for providing bicarbonate-based solutions to patients during dialysis therapy.

Yet another advantage of the present invention is to provide medical treatments that employ improved bicarbonate-based solutions to treat, for example, acute renal failure during continuous renal replacement therapy.

A further advantage of the present invention is to provide two-part bicarbonate containing solutions that can be readily and sterilely formed to facilitate their use during medical therapy, particularly in an intensive care setting.

A still further advantage of the present invention is to provide a multi-chamber container that separately houses bicarbonate and electrolyte concentrates such that ready-to-use bicarbonate based formulations can be prepared by mixing the bicarbonate and electrolyte concentrates in the multi-chamber container thereby effectively eliminating the need to add one or more components, such as potassium chloride, to the bicarbonate based formulation via manual injection.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides improved bicarbonate-based solutions that can be effectively administered to a patient during medical therapy, particularly dialysis therapy. The bicarbonate containing solution of the present invention includes at least two separate components including a bicarbonate concentrate and an electrolyte concentrate which can be readily and sterilely mixed to form a ready-to-use formulation for patient administration. The bicarbonate-based solution can be effectively utilized in a number of different medical applications including, for example, dialysis therapy.

With respect to dialysis therapy, the present invention can be used in a variety of different dialysis therapies to treat kidney failure. Dialysis therapy as the term or like terms are used throughout the text is meant to include and encompass any and all forms of therapies that utilize the patient's blood to remove waste, toxins and excess water from the patient. Such therapies, such as hemodialysis, hemofiltration and hemodiafiltration, include both intermittent therapies and continuous therapies used for continuous renal replacement therapy (CRRT). The continuous therapies include, for example, slow continuous ultrafiltration (SCUF), continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), continuous venovenous hemodiafiltration (CVVHDF), continuous arteriovenous hemofiltration (CAVH), continuous arteriovenous hemodialysis (CAVHD), continuous arteriovenous hemodiafiltration (CAVHDF), continuous ultrafiltration periodic intermittent hemodialysis or the like. Further, although the present invention, in an embodiment, can be utilized in methods providing a dialysis therapy for patients having chronic kidney failure or disease, it should be appreciated that the present invention can be used for acute dialysis needs, for example, in an emergency room setting. Lastly, as one of skill in the art appreciates, the intermittent forms of therapy (i.e., hemofiltration, hemodialysis and hemodiafiltration) may be used in the in center, self/limited care as well as the home settings.

In an embodiment, the bicarbonate-based solution can be used as a dialysate during any suitable dialysis therapy. In an embodiment, the solutions of the present invention can be administered or infused to a patient as a replacement solution, infusion solution or the like during dialysis therapy, particularly during continuous renal replacement therapy. As previously discussed, replacement solutions, infusion solutions or the like must necessarily be continuously fed to a patient as a substitute for an excessive amount of plasma water that is typically removed during continuous renal replacement therapy. In this regard, a proper water balance in the patient's body can be effectively maintained.

In an embodiment, the bicarbonate-based solution includes sodium (Na.sup.+), calcium (Ca.sup.++), magnesium (Mg.sup.++), potassium (K.sup.+), bicarbonate (HCO.sub.3.sup.-), chloride (Cl.sup.-), lactate (CH.sub.3CHOHCOO.sup.-), acetate (CH.sub.3COO.sup.-), anhydrous glucose or dextrose, hydrous glucose or dextrose, like constituents and combinations thereof. The solution can include any suitable and physiological acceptable and effective amounts of the constituents. The term "physiological acceptable" as used herein means any suitable amount of a constituent or constituents of the bicarbonate based solution of the present invention (e.g., potassium, sodium or the like) that can be administered to a patient in a safe, acceptable and/or tolerable manner.

In an embodiment, the solution includes about 100 mmol/L to about 160 mmol/L of sodium, preferably about 130 mmol/L to about 150 mmol/L of sodium; about 0 mmol/L to about 2.0 mmol/L of calcium, preferably about 0 mmol/L to about 1.75 mmol/L of calcium, more preferably about 0.2 mmol/L to about 2.0 mmol/L of calcium; about 0 mmol/L to about 1.5 mmol/L of magnesium, preferably about 0.25 mmol/L to about 0.75 mmol/L of magnesium; about 0 mmol/L to about 5 mmol/L of potassium, preferably about 0 mmol/L to about 4 mmol/L of potassium; about 20 mmol/L to about 45 mmol/L of bicarbonate, preferably about 25 mmol/L to about 35 mmol/L of bicarbonate; about 70 mmol/L to about 130 mmol/L of chloride, preferably about 70 mmol/L to about 120 mmol/L of chloride, more preferably about 91 mmol/L to about 128 mmol/L of chloride; about 0 mmol/L to about 45 mmol/L of lactate, preferably about 0 mmol/L to about 35 mmol/L of lactate; about 0 mmol/L to about 45 mmol/L of acetate, preferably about 0 mmol/L to about 35 mmol/L of acetate; about 0 g/L to about 2.5 g/L glucose, preferably about 0 g/L to about 2.0 g/L of glucose; or combinations thereof. Applicants have found that the bicarbonate-based solutions of the present invention are stable for over a six month period at a physiological acceptable pH ranging from about 6.5 to about 8.0 at 25.degree. C., preferably at a pH ranging from about 7.1 to about 7.4.

As previously discussed, the bicarbonate-based solution of the present invention includes a number of constituents or components that are separately housed such that the components can be readily and sterilely mixed to form the resulting bicarbonate-based solution. Applicants have discovered that the bicarbonate-based solution of the present invention can eliminate the need of excessive handling of one or more of its components prior to mixing as compared to conventional solutions which necessarily require a physician or other medical care provider to manually inject one or more components, such as bicarbonate, potassium chloride and the like, during the formulation of the bicarbonate solution.

In this regard, the ready-to-use bicarbonate-based formulations of the present invention can decrease the amount of time and effort with respect to the preparation and administration of the formulations of the present invention as compared to conventional bicarbonate formulations. The ready-to-use formulations of the present invention can also effectively eliminate, or at least greatly minimize, the potential of the spread of biological contamination during the preparation, administration and/or general use thereof. Such attributes of the bicarbonate-based formulations of the present invention are desirable as applied to medical therapies, particularly in an intensive care setting.

It should be appreciated that the components of the solution can be housed or contained in any suitable manner such that the bicarbonate-based solutions of the present invention can be effectively prepared and administered. In an embodiment, the present invention includes a two part bicarbonate-containing solution in which each part or component are formulated and stored separately, and then mixed just prior to use. A variety of containers can be used to house the two part bicarbonate-containing solution, such as separate containers (i.e., flasks or bags) that are connected by a suitable fluid communication mechanism. In an embodiment, a multi-chamber container or bag can be used to house the separate components of the solution.

FIG. 1 illustrates a suitable container for storing, formulating and administering a bicarbonate-based solution of the present invention. The multi-chamber bag 10 has a first chamber 12 and a second chamber 14. The interior of the container is divided by a heat seal 16 into two chambers. It should be appreciated that the container can be divided into separate chambers by any suitable seal. In an embodiment, the container can be divided into separate chambers, such as two chambers, by a peel seal. The multi-chamber container 10 also has a frangible connector 18 to sealingly couple the first chamber 12 to the second chamber 4. To mix the solution within the multi-chamber bag 10, the frangible connector 18 is broken.

The first container or chamber 12 includes two port tubes having, for example, different lengths. As shown in FIG. 1, the short port tube 20 can be utilized to add other constituents to the first chamber 12 during formulation of the solution of the present invention, if necessary. The long port tube 22 can be utilized to adaptedly couple the first chamber 12 to the patient via, for example, a patient's administration line (not shown). The second container or chamber 14 has a single port tube 24 extending therefrom which is closed by, for example, a solid rod (not shown). In this regard, it is not possible to add any additional constituents to this chamber and/or connect this chamber to a patient's administration line such that the chamber 14 cannot be adapted to deliver its constituents to the patient.

In an embodiment, the transfer of product within the multi-chamber bag 10 is thereby initiated from the second chamber 14 to the first chamber 12 such that the components of each chamber can be properly mixed to form the bicarbonate-based solution of the present invention. In this regard, the first chamber 12 is larger in volume than the second chamber 14 such that the components of each chamber can be properly mixed once the transfer from the second chamber to the first chamber has occurred. Thus, the multi-chamber bag 10 can house at least two non-compatible solutions that after mixture will result in a ready-to-use dialysis solution. An example of the multi-chamber container is set forth in U.S. Pat. No. 5,431,496, the disclosure of which is incorporated herein by reference. The multi-chamber bag can be made from a gas permeable material, such as polypropylene, polyvinyl chloride or the like.

It should be appreciated that the multi-chamber bag can be manufactured from a variety of different and suitable materials and configured in a number of suitable ways such that the bicarbonate-based solution of the present invention can be effectively formulated and administered to the patient during medical therapy. For example, the second chamber can be larger in volume than the first chamber such that the bicarbonate-based solution of the present invention can be readily and effectively made and administered to the patient from the second chamber.

Although the multi-chamber container disclosed herein is designed to be used for any medical procedure that requires bicarbonate, the embodiment illustrated in FIG. 1 is conveniently used for dialysis therapy including, for example, continuous renal replacement therapy. To this end, in an embodiment, the components of the bicarbonate-based solution of the present invention are separately housed in either of the first chamber 12 and the second chamber 14 such that a mixed solution of the components of the first chamber 12 and the second chamber 14 can be sterilely and readily formed upon mixing within the multi-chamber container.

In an embodiment, the first chamber 12 contains a bicarbonate concentrate and the second chamber 14 contains an electrolyte concentrate. The bicarbonate and electrolyte concentrates can include any variety of different and suitable constituents in varying and suitable amounts such that, when mixed, a desirable and suitable bicarbonate based solution can be formed. In an embodiment, the bicarbonate concentrate includes sodium chloride (NaCl), sodium hydroxide (NaOH), sodium bicarbonate (NaHCO.sub.3), the like or suitable combinations thereof, and the electrolyte concentrate includes hydrated calcium chloride (CaCl.sub.2.2H.sub.2O), hydrated magnesium chloride (MgCl.sub.2.6H.sub.2O), sodium chloride (NaCl), potassium chloride (KCl), glucose including, for example, anhydrous glucose or dextrose, hydrous glucose or dextrose, the like or suitable combinations thereof.

It should be appreciated that the bicarbonate and electrolyte concentrates can include any suitable pH such that a physiological acceptable pH of the final or reconstituted bicarbonate-based solution can be achieved. In an embodiment, the bicarbonate-based solution can be formulated under moderate or extreme pH conditions. It should be appreciated that the bicarbonate-based solution can be formulated in any suitable manner under moderate or extreme pH conditions.

For example, in an embodiment, the bicarbonate-based solution can be formulated under extreme pH conditions as disclosed in U.S. Pat. No. 6,309,673, the disclosure of which is incorporated herein by reference. Such a formulation allows the product to be packaged without an over pouch.

In an embodiment, the bicarbonate-based solution of the present invention is formulated under moderate pH conditions. Preferably, such a product is placed in a container that includes a gas barrier over pouch.

Under moderate pH conditions, the bicarbonate-based solution of the present invention is formulated by the mixing of a bicarbonate concentrate with a pH ranging from about 7.2 to about 7.9, preferably from about 7.4 to about 7.6, and an electrolyte concentrate with a pH ranging from about 3.0 to about 5.0, preferably from about 4.3 to about 4.5. Under extreme pH conditions, a bicarbonate concentrate with a pH ranging from about 8.6 to about 9.5, preferably from about 8.9 to about 9.0, is mixed with an electrolyte concentrate having a pH that ranges from about 1.7 to about 2.2, preferably about 1.9.

A variety of different and suitable acidic and/or basic agents can be utilized to adjust the pH of the bicarbonate and/or electrolyte concentrates. For example, a variety of inorganic acids and bases can be utilized including hydrochloric acid, sulfuric acid, nitric acid, hydrogen bromide, hydrogen iodide, sodium hydroxide, the like or combinations thereof.

As previously discussed, the present invention provides method and systems for effectively providing a bicarbonate containing solution to a patient during medical therapy. In an embodiment, the present invention can be effectively utilized to treat acute renal failure, particularly with respect to critically ill patients in an intensive care setting. In this regard, Applicants have uniquely discovered that the present invention can provide ready-to-use bicarbonate-based solutions that can be effectively and sterilely administered to the patient during therapy. The ready-to-use formulations can include a number of integrated mechanisms to facilitate the safe and effective use of the bicarbonate-based solutions of the present invention during medical therapy.

In an embodiment, the bicarbonate concentrate and the electrolyte concentrate include a physiological acceptable amount of sodium. To achieve the physiological acceptable level of sodium, the sodium chloride content can be distributed between the bicarbonate concentrate and the electrolyte concentrate such that each contains an equimolar and physiological acceptable concentration of sodium.

In an embodiment, the equimolar amount of sodium is about 160 mmol/L or less. In an embodiment, the equimolar amount of sodium is about 100 mmol/L or more. In an embodiment, the equimolar amount sodium ranges from about 100 mmol/L to about 160 mmol/L, preferably from about 130 mmol/L to about 150 mmol/L, more preferably about 140 mmol/L. In this regard, if the concentrates remain unmixed prior to patient administration (i.e., the frangible connector remains unbroken), this would necessarily ensure that the patient is not overloaded with sodium through the administration of, for example, the bicarbonate concentrate which can be directly coupled to the patient.

As previously discussed, the first chamber 12 of the multi-chamber bag 10 contains the bicarbonate concentrate. In an embodiment, the bicarbonate concentrate includes a physiological acceptable buffered solution of bicarbonate. This ensures that the patient is not overloaded with a number of electrolytes if, for example, the bicarbonate concentrate is separately and mistakenly administered to the patient. This can occur if the frangible connector remains unbroken and, thus, the bicarbonate concentrate and electrolyte concentrate are not mixed prior to administration to the patient where the bicarbonate concentrate is contained in a chamber which is directly coupled to the patient.

In an embodiment, potassium is solely contained in a chamber of the multi-chamber container of the present invention which physically cannot be placed in direct access to the patient. In this regard, the potassium cannot be placed in direct fluid communication with the patient without mixing with the other components of the solution. For example, in an embodiment, the bicarbonate concentrate which can be placed in direct fluid communication with the patient does not contain potassium, such as potassium derived from, for example, potassium chloride or the like. In an embodiment, the potassium chloride is contained solely in the electrolyte concentrate to ensure that the patient cannot receive an undesirable concentration thereof if, by chance, the bicarbonate concentrate and the electrolyte concentrate were not mixed prior to patient administration. In this regard, the bicarbonate-based solution of the present invention can be configured such that the patient cannot receive the electrolyte concentrate directly but rather as a part of a mixed solution of the bicarbonate concentrate and the electrolyte concentrate.

It should be appreciated that a variety of suitable and additional configurations of the present invention can be utilized to facilitate the safe and effective administration of the bicarbonate-based solution to a patient during therapy. In an embodiment, any physiological acceptable amounts of one or more electrolytes can be contained within a chamber of the multi-chamber container (e.g., the first chamber 12 of the multi-bag container 10 as discussed above) of the present invention which can be placed in direct access or fluid communication with the patient. For example, the chamber that can be placed in direct fluid communication with the patient can include a physiological acceptable amount of potassium, sodium, the like or combinations thereof. In an embodiment, the chamber that can be placed in direct access or fluid communication with the patient does not include potassium or the like. In an embodiment, the chamber that can be placed in direct access or fluid communication with the patient houses the bicarbonate concentrate of the present invention.

In an embodiment, each of the bicarbonate concentrate and the electrolyte concentrate include a physiological acceptable amount of potassium prior to mixing such that the resultant solution of bicarbonate and electrolyte concentrates contains a desirable and suitable level of potassium ranging from about 0.1 mmol/L to about 5 mmol/L.
 

Claim 1 of 11 Claims

1. A two part dialysis solution comprising: a bicarbonate concentrate; and an electrolyte concentrate, wherein the bicarbonate concentrate and the electrolyte concentrate include a physiological amount of sodium ranging from 100 mmol/L to 173 mmol/L, and wherein the two part dialysis solution does not include acetate, wherein a mixed solution of the bicarbonate concentrate end the electrolyte concentrate further comprises about 0 mmol/L to about 2.0 mmol/L of calcium, about 0 mmol/L to about 1.5 mmol/L of magnesium, about 0 mmol/L to about 5 mmol/L of potassium, about 20 mmol/L to about 45 mmol/L of bicarbonate, about 70 mmol/L to about 130 mmol/L of chloride, about 0 mmol/L to about 45 mmol/L of lactate, and about 0 g/L to about 2.5 g/L of anhydrous glucose.

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