1. Field of Invention
The subject matter of the invention is a multichamber bag for holding concentrates and preparing a medicinal solution of the concentrates as well as a method for preparing a medicinal solution from several concentrates.
2. Description of the Prior Art
Patients in renal failure suffer from restricted functioning of the kidneys so that the required excretion of urine-bound substances from the patient's body is prevented. Toxic metabolites must be removed from the patient by purifying the blood in a dialysis treatment. In dialysis, the blood is purified through a mass exchange membrane which comes in contact with the patient's blood on one side and with a cleaning fluid on the other side. The cleaning fluid is the so-called dialysis solutions which take up certain substances intended for secretion and remove them from the patient's blood. In general, dialysis solutions consist of an aqueous composition of physiologically important dissolved components, electrolytes, buffers or osmotically active reagents such as glucose, for example.
In peritoneal dialysis (PD), the dialysis solution is infused into the peritoneum of the patient. The patient's diaphragm then serves as a mass exchange membrane through which the blood is purified. The mass transport is determined by diffusive transport processes of urinary substances from the blood side through the diaphragm membrane and into the peritoneum, which is filled with dialysis solution. An osmotic agent is added to the dialysis solution, so that a higher osmotic pressure prevails in the peritoneum than in the blood. Based on the osmotic pressure gradient, there is a transfer of water through the membrane into the space of the peritoneum. In the course of the treatment or toward the end of the treatment the peritoneum is emptied and the dialysis solution is discarded.
In hemodialysis (HD) the patient's blood to be cleaned is passed through an extracorporeal blood circulation and brought in contact with a mass exchange membrane. The opposite side of the mass exchange membrane is brought in contact with dialysis solution, so that membrane-permeable substances can be removed from the blood by membrane transfer with the dialysis solution. The process of mass transfer can take place through diffusive or convective transport processes in the conventional HD therapies. Through convective transport processes in particular it is possible to withdraw fluid from the patient, so that a solution for HD dialysis must in general have a lower osmotic pressure for cleaning of the blood than solutions suitable for PD dialysis.
In the case of both HD and PD dialysis, the dialysis solutions contain typical dissolved substances, for example:                electrolytes Na, K, Mg, Ca to maintain an acceptable electrolyte balance for the patient;        buffers (for example bicarbonate, acetate, lactate . . . );        glucose (or other osmotic agents) as osmotic agent in peritoneal dialysis or for maintaining the blood sugar level during hemodialysis;        acids or salts of acids (for example HCl and/or Cl−, acetic acid, citric acid, . . . ), which might contribute toward neutralization of basic partial dialysis solutions or as counterions in the electrochemical equilibrium.        
The substances used for the dialysis solution cannot in general be stored in a ready-to-use mixture because the substances may cause mutual degradation. The required stability in storage of a component may presuppose storage conditions which result in degradation of other components. For example, glucose, depending on its concentration in solution, is storable for prolonged periods of time without being subject to unwanted degradation processes to an excessive extent only at a certain acidic pH. At the same time, the compound sodium bicarbonate, which is often used as a buffer in dialysis solutions is not stable in storage under such acidic conditions because bicarbonate tends to decompose as a function of the pH and can release CO2. Under decomposition conditions, the concentration of bicarbonate changes, which is unacceptable from a therapeutic standpoint. The increase in the CO2 partial pressure also makes demands of the medical dialysis equipment leading to technical problems.
A variety of alternative compositions, storage conditions and dosage forms of dialysis solutions or concentrates are known which enable a prolonged storage. It is known that the solution components can be divided into a combination of partial solutions or concentrates so that only acceptable components of a partial solution or of a partial concentrate are stored together. For peritoneal dialysis solutions, a first partial solution comprising glucose, which assumes the function of the osmotic agent, is usually stored at an acidic pH with additional electrolytes, for example, sodium, calcium, magnesium. Another basic or buffered partial solution is necessary to supply a physiological mixed solution that is ready-to-use at least for treatment from the first part and the second part when using the first acidic partial solution. The second part often consists of a solution or a concentrate of sodium bicarbonate and sodium chloride. The partial solutions or concentrates are stored in multiple containers or in multiple chambers of one container. The partial solutions or partial concentrates are present separately so that there is no mutual influence. Immediately prior to use of the dialysis solution, the separate partial solutions or partial concentrates are mixed, possibly adding additional aqueous components, and supplied for the treatment.
In hemodialysis the partial solutions or partial concentrates are often mixed in the dialysis machine before and during the course of the treatment and prepared to yield a finished dialysis solution. Partial concentrates in solid or liquid form which are present in individual containers and are diluted through a connection to the dialysis machine with the help of a prepared hydraulic system are mixed and prepared to the finished ready-to-use dialysis solution. For this purpose partial concentrates in solid or liquid form are often used; these are present in individual containers and are diluted, mixed and processed to yield the finished ready-to-use dialysis solution through a connection to the dialysis machine with the help of a prepared hydraulic system.
Other developments in dialysis have tended toward keeping the necessary concentrates in a single container. First of all, this simplifies preparation and handling of the containers, and secondly this also simplifies the hydraulic system of the dialysis machine because in the meantime only one holding unit is necessary for the partial solutions and fewer connections are necessary to process the solution through the hydraulic system. This trend can be observed in particular in acute dialysis because a greater mobility of the treatment system is required there.
In another variant dialysis solutions for hemodialysis are not prepared from concentrates during the course of the treatment but instead the total required volume of the dialysis solution is prepared in one batch in a step prior to the treatment. The batch is kept on stock in a tank which is prepared to be connected to a dialysis machine. In many cases the tank is an integral component of a dialysis treatment unit or in certain cases can also be moved again separately from it. Batch dialysis may thus have the advantage of selecting the treatment site relatively independently of location through a single preparation of the batch. Treatment stations at various locations can thus be used without having to rely on a preparation unit of dialysis solution or a water connection but supplies the required water for dilution of the concentrates. In these cases, the dialysis solution is mixed together from concentrates at an apparatus provided for this purpose and then is usually stored in a mobile tank.
It is known that the required concentrates for preparing a dialysis solution batch may be kept in just one drum unit. Thus, for example, there are known dry concentrates whose granular particles have a multilayer or multicomponent structure. Each layer of granules or each component contains the substances needed for preparation of the dialysis solution.
In another development different dry concentrates are placed in a drum unit. Various granules corresponding to different solution components are poured into a container layer by layer. The components in one layer are thus present essentially separately from the components of the next layer. Then they are in contact with components of the neighboring layers only through the interfaces between two neighboring layers.
However, in reviewing these developments, it has been found that even in the case of such a layered structure of a granular particle or in a layered presentation of dry concentrates of corresponding solution components, negative interactions may occur among the various concentrates.
Dry concentrates make increased demands in storage in comparison with partial solutions or solution-type partial concentrates. The dry concentrates must not only overcome the aspect of degradation of parts of the concentrates of the solution components during their guaranteed storage time but must also be able to fulfill the aspect of good solubility with a diluent. Observations from the state of the art in storage of dry concentrates have shown that particulate concentrates may undergo agglomeration under the influence of moisture. In an agglomerated state, however, the concentrate is not readily miscible with another aqueous diluent, so that the solution times of such concentrates in clinical use may not be acceptable. The prerequisite is thus that concentrates, in particular when they are dry concentrates, must be rapidly and thoroughly miscible with diluents or other solutions.
An all-purpose concentrate, which contains all the ingredients required for dialysis, is not usually stable in storage. Therefore the concentrate is separated into partial concentrates so that only solution components that are compatible and stable in storage with one another are present in each partial concentrate. A set of concentrates or partial solutions prepared for producing medicinal solutions may thus consist of two, three or more partial concentrates or partial solutions which are stored in a container or bag.
EP 1 458 433 discloses a concentrate container in which the solution components or partial concentrates are arranged in layers and therefore mutually incompatible components are separated from one another.
EP 1 059 083 discloses granules in which the grains have a layered structure. Mutually incompatible solution components can be kept separate from one another by soluble buffer layers.
WO 2007/144427 discloses a system for producing dialysis solutions using a multichamber bag containing a partial concentrate in each chamber. By adding a fluid, the dividing lines between the chambers are broken and the dialysis solution is prepared.
U.S. Pat. No. 4,386,634 discloses a large-volume container, in which dry concentrates for preparing a dialysis solution are stored. By adding water a liquid concentrate is prepared.
U.S. Pat. No. 7,544,301 and EP 0 846 470 disclose methods for monitoring the dissolving process in the preparation of a batch of a dialysis solution based on electrical conductivity measurements.
It is described in the state of the art that different partial concentrates or partial solutions may be used for preparation of dialysis solutions in a multicompartment container. Adequate stability in storage cannot be achieved in storage of the components of the solution, divided among various partial concentrates or partial solutions. The partial concentrates or partial solutions are stored in different containers or in different chambers of a container. The chambers are separated from one another by separating means. The contents are released by dissolving the separating means and yield a finished ready-to-use medicinal solution by aqueous dilution or simple mixing, for example.
For monitoring the preparation process of medicinal solutions, it is important to have clarity about whether all the partial concentrates were mixed in the process. In general the dissolving process and/or dilution process of the partial concentrates is easy to monitor by measuring the electrical conductivity. If the partial concentrates contain ionic substances, then they make a contribution toward the electrical conductivity when dissolved and/or diluted. An end to the dissolving process may be indicated in particular by achieving a final conductivity value in the solution/dilution process. It is thus possible to reliably conclude that all partial concentrate parts or solution parts have been mixed and no other partial concentrates or partial solutions are present in undissolved and/or unmixed form. Similarly, a conductivity value, which does not correspond to a previously defined final conductivity value indicates that a partial concentrate or partial solution may not have been diluted and/or mixed. A monitoring unit may thus be used in an action mode so that an alarm or additional dissolving steps are initiated, for example.
However, the conductivity measurement may provide inadequate information if individual concentrates make only a very minor contribution to the conductivity or none at all. In the worst case, a final conductivity value may already be indicated in the process of preparing the solution, although components of the solution which do not make any contribution toward the electrical conductivity are undissolved, unmixed or undiluted. Solution components which are used for medicinal solutions and can make only a minor contribution toward the electrical conductivity of an aqueous mixed solution or none at all, for example, organic substances, may include:                active ingredients, pharmaceutical drugs;        in particular osmotic agents in the dialysis field: glucose, fructose, galactose, amino acids; acids: acetic acid, citric acid, lactic acid, succinic acid, fumaric acid, oxalic acid, malic acid . . . .        
In this technical context the term “low electrical conductivity” is understood to refer to aqueous solutions which have a conductivity value of 0.5 mS/cm or lower. Or these are compositions, for example, concentrates with or without diluents or partial solutions or suspensions, which cause a conductivity change of 0.5 mS/cm or less in an expected solution after dilution. In this sense, the aforementioned organic acids are also to be classified as substances which make this low conductivity contribution to the total solution, depending on the concentration.
Thus there is the problem of monitoring the dissolving process of multiple concentrates, solutions or partial solutions by conductivity measurements, such that at least one of the concentrates consists of substances which do not make any contribution toward the electrical conductivity in the ready-to-use solution.
USPTO Backgrounds
USPTO Backgrounds