JPS58500563A - Dialysate containing glucose, amino acids and insulin - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] Dialysate technology field including glucose, amino acids and insulin Currently, hundreds of patients with end-stage renal disease who have lost or damaged kidney function are being treated by dialysis procedures. I'm still alive. Many patients survive with hemodialysis, others with peritoneal dialysis, e.g. For example, continuous ambulatory peritoneal dialysis (C He is survived by a medical procedure known as APD. This latter technique Clinical use as the technique of choice for the survival of large numbers of patients with lost or damaged function. Its use is rapidly expanding.

In a CAPD operation, peritoneal dialysis fluid is injected into the peritoneal cavity, thereby dissolving the solution and blood. Diffusion exchange occurs across the natural body between the bloodstream and The waste products excreted from substances, as well as other substances normally excreted by the body, such as urea and creatinine. water is removed.

The types and proportions of substances removed from the living body by peritoneal dialysis are determined by the amount present in the peritoneal dialysis fluid. This is a relationship between the solutes present. chloride) IJium, sodium lactate and sodium acetate Physiological salts such as calcium generally have slightly hypotonic concentrations (with the exception of calcium). The excess of ions present in the peritoneal dialysis fluid and thus forming such a contaminant in the bloodstream Excess concentration will diffuse into the desorption solution for removal.

to generate the necessary osmotic pressure to remove water from the patient as is generally required. Other solutions can be added to the sea urchin. In a typical WI dialysate, This solute is glucose, which is typically 0.5 to 4.25 am can be present in the dialysate at a concentration of %. Ultrasonic flow of water from the patient If promotion 1 is desired, high sugar concentrations within this range are used.

However, a drawback of this system is that water diffuses into the peritoneal dialysate during the peritoneal dialysis procedure. Le-a’l! The sugar present in the dialysate diffuses into the bloodstream to a small extent. . Therefore, this system is safe but not effective for increasing peritoneal dialysis. However, patients receive a high calorie burden from the sugar that diffuses into the bloodstream during each peritoneal dialysis procedure. Take the yōgyō uke. This is often associated with weight gain and obesity, as well as plasma lipids. This high caloric dose is undesirable as it results in an increased number of especially if you have diabetes , transfer of significant amounts of sugars, such as glucose, from the WjIFIk dialysate into the patient's bloodstream. This can lead to complications in the patient's medical survival.

The components of the solutions of the invention are all individually known as components of parenteral solutions; Not all of them have ever been used as components of dialysate. For example, The Lan On page 812 of the October 12, 1968 issue of ce; It is predicted that amino acids will be added to the dialysate of patients undergoing regular peritoneal dialysis therapy. and? Reporting. As stated in it: 1. Many amino acids are transported by the a-membrane easily absorbed. however, it passes through the peritoneum or other membranes to enter the bloodstream. Difficulties in assimilating free amino acids may be encountered. Chronic high levels of amino acids in the ml stream Amino acids are toxic and dangerous, and patients with end-stage renal disease can eliminate excess plasma amino acid concentrations through the kidneys. It is known that it cannot be excreted.

Therefore, many patients with renal failure are known to have chronic negative nitrogen balance. However, the amine rilt is added to the dialysate so that the amino acids pass into the bloodstream. Problems are not always easily solved by doing so.

Similarly, 25% of patients with end-stage renal disease who have diabetes mellitus receive peritoneal dialysis therapy. Their survival may be difficult, and immersion is recommended to remove water from the patient. Relatively high glucose levels have traditionally been added to peritoneal dialysis solutions to increase osmotic pressure. Considering the concentration, it is possible that it may have serious side effects. Glucose is in the patient's bloodstream Transition to and encourage during the above? bring it up.

According to the invention, the addition of insulin to the solution is a substitute for glucose and Npaku? Provides benefits associated with both the assimilation of amino acids into cells to produce do. These are known functions of insulin, but until now patients have not been able to combinations in the dialysate to simultaneously facilitate the metabolism of acid and glucose or other sugars. It has never been used as a combination ingredient.

As a result, the osmolality of the solution is increased so that ultrafiltration of water from the patient occurs during the dialysis procedure. Initially measured amounts of amino acids and glucose were used in the lI & dialysate to increase can be used.

After this, insulin absorbs glucose and glucose, which diffuses from the dialysate into the patient's bloodstream. Works to facilitate the metabolism of amino acids. The amount of insulin you need is can be predetermined depending on the concentration of amino acids and substances in the diabetes mellitus For the combined benefit of dialysis in protein-deficient uremic patients, pre-measured lysate The fluid can be prepared for dialysis operation, and if the patient is diabetic. delivered without having to recalculate their regular insulin dosing schedule. Their substitution of amino acids and sugars facilitates the receipt of optimal amounts of insulin. take. It is also possible to use a smaller shield by partially or completely substituting amino acids. I can do it.

Description of the invention According to the invention, for administration to a patient, typically for use as a dialysis fluid. A medical solution is provided. The solution should be sufficiently concentrated to be osmotically compatible with blood. A bathing liquid with the presence of physiological saline at a certain degree. Also, a mixture of physiological amino acids Contains, and carbohydrate nutrients such as glucose are present in the diet. Also diabetes carbohydrate nutritional sources, and amino acids when present, by other types of patients. Insulin is added at a rate sufficient to allow substantial assimilation. If desired It can be used as an equivalent substitute for other sugar alcohols such as fructose. can be done.

Charcoal mataglucose polymers and other sugar alcohols such as glycerol Can be used as a hydrate nutrient source. "Glucose" used below The term is intended to include these chewable materials as alternatives.

A relatively high osmolarity is desired for this solution to facilitate ultra-salt passage of water from the patient. It is not specifically intended for use as a peritoneal dialysis solution, but it may be used as an intravenous nutrient solution or It can also be used as a hemodialysate.

Initially, the mixture of glucose and amino acids had a high external oral permeability? Osmotic pressure increasing agent for providing It acts as. During the dialysis procedure, amino acids, glucose and insulin are diffuses into the bloodstream. Therefore, glucose and amino acids provide nutrients to the patient. , glucose and amino acids are present in the prior art operation due to the presence of insulin. Therefore, it is possible to reverse the negative nitrogen balance typically seen in treated renal failure patients. And it is easily provided to help you.

The pre-measured amount of insulin present in this medical solution is His prescribed dose of insulin is given without changing his usual therapy. This solution also aids in the management of diabetic patients as it facilitates the assimilation of glucose. Ru. Instead, all of the patient's insulin needs are met with insulin in the solution of the present invention. The patient receives continuous daily CAPDf, changing the dialysate several times each day. This can reduce the number of injections that patients themselves have to receive. Ru.

The solutions of the present invention are typically contained in separate, interconnected container systems, each in a After separate sterilization of separate solution parts containing glucose and amino acids, the system Sterile condition? Can be pre-mixed by mixing without breaking . This circumvents known incompatibility issues encountered when sterilizing mixtures of sugars and amino acids. avoid

Instead, the glucose and amino acid solutions are sterilized separately in separate containers and then to aseptically mix the two solutions to produce the medical solution of the invention. No. 4,157,723, which provides a reliable sterile connection for may be combined by the use of sterile connectors and other similar sterile connectors.

As a further alternative, glucose and amino acid solutions can be prepared in a substantially sterile but However, pre-mixing immediately before injection is not necessarily required under completely sterile conditions. I can do it.

Preferably, the amount of glucose or equivalent in the solution of the invention is 0°5 to 4y/ preferably contains at least 50% by weight of essential amino acids and optionally other non-essential amino acids. Amino acid mixture containing essential amino acids or 41! can exist with /l Wear. For example, Travenol Laboratories, Tierfield, Illinois; Found in the ``Travasol'' amino acid solution sold by Encophorated. A mixture of amino acids can be used to formulate the solutions of the invention, or or any other available amino acid mixture for parenteral administration. Ru. To this, for the above-mentioned beneficial purposes, preferably an infusion of You can add turin.

The term amino acid refers to short chain polypeptides suitable as equivalent substitutes for free amino acids. intended to include peptides.

Typically, the concentration of glucose is typically up to 4,25% found in prior art solutions. can be reduced in this manner from high glucose concentrations, while the presence of amino acids The osmotic pressure of the yoshi solution can be kept high. In this way, we can provide better care to patients. A dialysate having the desired hyperosmotic pressure combined with a nutrient mix is provided, in which nutrients are better assimilated or metabolized by the patient due to the presence of insulin. Ru.

Preferably, the medical solution of the invention contains 130 to 140 mEcy of sodium. '1. Chlorine 100 to 1 40 mEq//, Calcium 0 to 6 mF, q/l, magnesium 0 to 4 mEq/l, and if desired, lactic acid, 30 to 30% of bicarbonate precursors such as acetic acid, malic acid and/or succinate ions It consists of an aqueous solution containing 40 mEq/l and having a pH of 5.0 to 7.4.

The ions are added according to known requirements for proper ion balance in the dialysate. Added sodium chloride, calcium chloride, sodium lactate, sodium acetate , plus common physiological salts like potassium chloride, magnesium chloride and other trace amounts. It can be supplied by the addition of

The osmolality of the solution according to the invention is between 272 and 700 mOsmol/l, preferably between 2 79 to 480 mOsmol/l is generally preferred.

The precursor acid ions to the aforementioned heavy carbon #, and other acid ions in the Kreves cycle, are present in the present invention. can be added to provide benefits in pH control of peritoneal dialysis solutions. Ru. For example, the sodium or potassium salts of such ions, or free 1I f - can be used for this purpose. Sulfhydryl type antioxidants, such as N- Acylcysteine is added to stabilize amino acids in the peritoneal dialysis fluid of the present invention. be able to.

Description of preferred specific examples Preferably, the peritoneal dialysis solution according to the invention contains 11 parts water, 5.55 parts sodium chloride. y, sodium lactate 3.92y, calcium chloride dihydrate 0.257y, chloride mag of nesium hexahydrate 0.152y, glucose 1y, essential and other amino acids Prepared by adding 3.25y of the mixture, and 3 units of 11 diinsulin. Articles can be made.

As mentioned above, the various components of the solution include glucose on one side and amino acids on the other. can be separated for separate sterilization into two solutions, one on the other. Each solution 2, connected by tubing so that the fluids can be sterilized separately and any desired Place in a conventional flexible soakable container sealed by an internal tube seal. be able to. Then break the inner seal of the tube and pour the solution into the tube by breaking the sterile seal. can be combined into a single solution of the present invention without any complications.

The solution container ultimately used to store the mixed sterile solution of the present invention is substantially Top made of polypropylene plastic, e.g. U.S. Pat. No. 4,232,7 It can be stored in a container having the structure shown in No. 21. connection tube to the other container. - It can be closed with a heat seal and separated using the container mixing method.

The foregoing is provided for illustrative purposes only and does not apply to the claims set out in the international search report.

Claims (1)

[Claims] 1. Physiological salts at a sufficient concentration to be osmotically compatible with blood and physiological amino acids. a mixture of acids and sufficient to permit substantial assimilation of said amino acids by the patient. an aqueous solution having a suitable proportion of insulin for administration to a patient. medical solution for treatment. 2. The solution of claim 1 containing a carbohydrate nutrient source. 3. The solution according to claim 2, which is a @desorption precipitation solution. 4. The solution of claim 3, wherein said carbohydrate nutrient source is glucose. 5. The solution according to claim 3, wherein the carbohydrate nutrient source is glycerol. 6. 0.5 to 4 y/l of the carbohydrate nutrients and a physiological amino acid mixture. Claim 3 comprising 42/l and 10 units of insulin. solution of. 7. Sodium 130 to 140 mEq//, chlorine 100 to 140 m Eq/1. Calcium 0 to 6 mEq/l and magnesium 0 to 4 The solution according to claim 3, comprising mEq/l. 8. At least one selected from the following: lactic acid, acetic acid, malic acid and succinic acid. A solution according to claim 3 containing 30 to 40 mEq/f of bicarbonate precursor ions. liquid. 9. A solution according to claim 3 having an osmotic pressure of between 272 and 700 milliosmoles. . 10, pns, o to 7.2, the solution according to claim 3. 11. N-acylcysti in an amount sufficient to improve the stability of the amino acids present. 4. A solution according to claim 3, comprising a sulfhydryl type antioxidant, such as a sulfhydryl type antioxidant.