FR2628318A1 - Solid, esp. granular, compsn. for prepn. of haemodialysis soln. - contg. sodium, potassium, calcium, magnesium, acetate and chloride ions, providing solns. of reproducible compsn. - Google Patents

Abstract

Pharmaceutical compsn. for prepn. of haemodialysis solns. is in solid, esp. granular, form. Solns., conc. or dilute, prepd. by diluting this compsn. with sterile water are also new. The compsn. contains Na, K, Ca, Mg, acetate and chloride ions, opt. also hydrogencarbonate and acidic ions. It is esp. packaged in a plastic pouch. USE/ADVANTAGE - Solns. prepd. from this compsn. are used for extrarenal treatment of kidney : and for some cases of acute poisoning. Compared with use of liq. concentrates, the granular prods. provide a use soln. of more consistent composition and are easier to work with. Also, all components can be present in a single formulation (contrast 2 liq. concentrates, mixed just before use).

Description

PELLETS FOR HEMODIALYSIS
The present invention relates to a pharmaceutical composition in the form of granules for the preparation of solutes and to the solutes thus obtained, intended for the treatment of renal insufficiency by extrarenal purification.

Pharmaceutical preparations for hemodialysis commonly used in medical practice are presented in the form of concentrated solutes which must be diluted before administration to the patient so that the final concentration of ions per liter of the most common active ingredients is in the intervals. following
130 to 145.0 mmol for the Sodium ion
- from C to 3.0 mmol for Potassium ion
from 1.0 to 2.0 mmol for the Calcium ion
from 0.25 to 1.0 mmol for the magnesium ion
from 32 to 40 mmol for the Acetate ion
from 95 to 115 mmol for the chloride ion.

 However, repeated measurements have shown that these solutions frequently exhibit variations of + or - 2.5% for the Sodium ion and + or - 5% for the other constituents (Potassium, Calcium, Magnesium and Chlorine ions). ). These variations in ionic concentrations of important elements, however weak, are likely to cause serious disorders on weakened organisms.

 The method of the invention makes it possible to overcome this important disadvantage.

Indeed, the solid form of the granules of the invention provides a better homogeneity and greater reliability in the composition.

 The granular form of the invention additionally has the advantages of great ease in handling, filling and packaging in plastic bags as well as in the preparation of concentrated solutes or dialysate ready for administration after dilution with the sterile water.

In addition, a number of preparations of this type are often presented as two concentrated solutions A and B which should be mixed only at the time of use in different proportions according to the purpose. Thus, for example, solutions A containing sodium hydrogen carbonate and sodium chloride and solutions B containing acetic acid and chlorides of sodium, calcium, magnesium and
Potassium. In this type of extemporaneous mixing preparations (sodium hydrogen carbonate is decomposed in an acidic medium), the granular form makes it possible to make a single final product by replacing the acetic acid with an acid in solid form.

 The preparation of the granules is carried out in a conventional manner: the various components are sieved and the granulation is obtained in the presence of a solvent in a conventional granulator mixer. The granulate is then dried in such a way that the residual humidity is less than 1 96. It is then sieved, if necessary.

 The following nonlimiting examples are given by way of illustration of the invention.

 1. Preparation of a granulate with sodium acetate.

 The quantity of granules sufficient for making thirteen plastic bags is prepared, each bag providing, by dilution, the quantity of solute required for a hemodialysis session.

 17.803 Kg Sodium acetate were passed through a sieve of about 1250 um mesh opening and then dried in a dryer at a temperature not exceeding 130oc.

The dried sodium acetate is then mixed with the sieved sodium chloride in the same manner and the. The mixture thus prepared is introduced into a granulator mixer. The solution A and then the solution B are then sprayed under vacuum continuously for about 3 minutes while stirring at 150 rpm.
- solution A: Calcium chloride 0.760 Kg
Magnesium chloride 0.376 Kg
acetic acid 0.028 Kg
purified water 0.600 Kg
- solution B: potassium chloride 0.331 Kg
purified water 1,187 Kg.

 The drying is then carried out under vacuum in a dryer at a temperature which must not exceed 1300 ° C. so that the residual humidity is equal to or less than 1 96 ° C.

 The granulate thus obtained is then screened through a vibrating sieve with a mesh size of 1250 μm and recovered in a moisture-tight container and then packaged in plastic bags.

The contents of each plastic bag having the composition below will be diluted as follows before use:

<tb> Acetate <SEP> of <SEP> Sodium <SEP> 3H, O <SEP> 1080.06 <SEP> g <SEP> 166.70 <SEP> g <SEP> 35 <SEP> mmol <SEP> 138 #l
<tb> Chloride <SEP> of <SEP> Sodium <SEP> 1366.72 <SEP> f <SEP><SEP> 210.68 <SEP><SEP> g <SEP> 1 (, 3 <SEP><SEP> total
<tb> Chloride <SEP> of <SEP> Calcium <SEP> 2H <SEP> O <SEP><SEP> 58.33 <SEP> g <SEP> 9.00 <SEP> g <SEP> 1.75 <SEP> mmol
<tb> Chloride <SEP> of <SEP> Magnesium <SEP> bH20 <SEP><SEP> 28.84 <SEP> g <SEP> 4.45 <SEP> g <SEP> 0.625 <SEP> mmol <SEP> 109.25 <SEP> mmol
<tb> Chloride <SEP> of <SEP> Potassium <SEP> 26.55 <SEP> g <SEP> 3.91 <SEP> g <SEP> 1.50 <SEP> mmol <SEP> of <SEP> Cl <SEP> total
<tb> Acid <SEP> Acetic acid <SEP> qs <SEP> pH <SEP> 7-7,8
<tb><SEP> For <SEP> 6.5 <SEP> 1 <SEP> 1 <SEP> liter <SEP> of <SEP> 1 <SEP> liter <SEP> of
<tb><SEP> of <SEP> concen- <SEP> Concentrate <SEP> solution <SEP> di
<tb><SEP> very <SEP> (envi- <SEP> read <SEP> at
<tb><SEP> ron <SEP> for <SEP> 1 <SEP> 1/35 <SEP> ready
<tb><SEP> meeting <SEP> of <SEP> for <SEP><SEP> dialysis
<tb><SEP> dialysis)
<Tb>
In order to verify the composition of the solutions obtained, controls are carried out under eight doses ceased This 8.23 and 82.25 g. The results of the assays are reported below.
a) 8.23 g (qs 25 ml of concentrate)
Na + K Ca.Mg Cl
Theoretical values 138 1.50 3.50 1.25 109.25
Averages 137.9 1.51 3.46 1.25 109.9
Deviation Type 0.694 0.0271 0.0729 0.0261 0.704
Precision (0.95) 1.19 4.26 4.99 4.95 1.52 for a test in
b) 82.25 g (qs 250 ml of concentrate)
Na h Ca ++ Mg Ci
Averages 138 1.50 3.48 1.25 109.7
Distance Type 0 0.00641 0.0259 0.00552 0.704
Accuracy (0.95) 0 1 1.76 1.04 1.52 for a test in
It can be seen that in the final product, the amounts of active ingredient used are found with great precision.

2. Preparation of granulation for hemodialysis with acid carbonate of
Sodium, acidified with an acid in solid form.

This granulate, after dilution, provides a solute whose composition per liter is as follows

<tb> Bicarbonate <SEP> of <SEP> Sodium <SEP> 3,275 <SEP> 39 <SEP>
<tb> Chloride <SEP><SEP> of <SEP> Sodium <SEP><SEP> 6,136 <SEP> 105 <SEP> mmol
<tb> Chloride <SEP> of <SEP> Potassium <SEP> IT <SEP> Na <SEP> total
<tb> Chloride <SEP> of <SEP> Calcium <SEP> 2H <SEP> O <SEP><SEP> 0.257 <SEP> 1.75 <SEP> mmol <SEP>
<tb> Chloride <SEP> of <SEP> Magnesium <SEP> gH2O <SEP><SEP> 0.127 <SEP> 0.625 <SEP> mmol <SEP> 110.75 <SEP><SEP> mmol
<tb> Citric acid <SEP><SEP> 2 <SEP> 4 <SEP> mmol <SEP> Cl <SEP> total
<Tb>
The sodium chloride is sieved and then introduced into a granulator mixer with stirring. Aqueous solution of the potassium, magnesium and citric acid salts is added. The granule is dried, sieved and then re-introduced into the mixer with sodium hydrogen carbonate for 20 minutes.

 From the end of drying, all operations must be carried out in a dehumidified atmosphere (moisture less than or equal to 30%) and the granule preserved in the absence of moisture to prevent the decomposition of sodium hydrogen carbonate. in the presence of citric acid.

 The controls carried out as above demonstrate the good stability of this preparation and a high fidelity in the composition.

Assay results on eight test portions of 10.13 g (qs 1 liter of dialysate)
Ka Ca Mg Cl Theoretical values 144 1 3.50 1.25 110.75
Averages iL3, ct 1,1 3,51 1,255 110,80
Difference Type 0.710 0.0201 0.0705 0.0230 0.702
Accuracy (0.95) 1.17 4.72 4.76 4.34 1.50 for a test in%
These solutes, prepared by dilution of the granules of the invention, are used in apparatus of the artificial kidney type. They are intended to constitute the bath against which will be dialyzed, by means of the artificial kidney, the plasma of the patient.

 They are used in the treatment of acute or chronic renal insufficiency and in certain acute intoxications.

Claims (7)

 1. Pharmaceutical composition for the preparation of hemodialysis solutes, CHARACTERIZED IN THAT it is presented in solid form.  2. Composition according to claim 1, CHARACTERIZED IN THAT the Bolide form is the granular form.  3. Composition according to claims 1 and 2, CHARACTERIZED IN THIS It contains Sodium, Potassium, Calcium, Magnesium, Acetate and Chloride ions.  4. Composition according to one of claims 1 to 3, CHARACTERIZED IN WHAT it contains acidic carbonate ions and acid ions.  5. Composition according to claim 4, CHARACTERIZED IN THAT the acidic ions are in solid form.  6. Composition according to one of claims 1 to 5, CHARACTERIZED IN WHAT it is packed in a plastic bag.  7. Concentrated or diluted solution, CHARACTERIZED IN THAT it is prepared by diluting the composition according to one of claims 1 to 5, with sterile water.