Dialysing and rinsing solution for intraperitoneal dispensing.
Abstract
Dialysier- und Spül-Lösungen zur intraperitonealen Verabreichung mit üblicher Elektrolytzusammensetzung in physiologischen Mengen und einem Aminosäuregemisch als osmotisch wirksame Substanz sowie gegebenenfalls zusätzlich organische Säure bzw. Salze derselben und gegebenenfalls weiteren Zusatzstoffen.
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15 claims: 1 independent, 14 dependent
- c-de-00011. Aqueous dialysis and rinsing solution for intraperitoneal administration containing electrolytes in physiological amounts, an amino acid mixture as osmotically active substance and optionally further additives, characterized In that the amino acid mixture, the following amino acids in the following relative amounts, expressed in parts by weight, contains:L-histidine 4 to 6 Parts by weight L-isoleucine 6 to 9 Parts by weight L-leucine 9 to 13.5 Parts by weight L-methionine 9 to 12 Parts by weight L-valine 13.5 to 20.5 Parts by weight L-lysine hydrochloride 6.5 to 10 Parts by weight L-phenylalanine 6 to 9.5 Parts by weight L-threonine 6.5 to 10 Parts by weight L-tyrosine 7.5 to 12 Parts by weight L-Taurine 2 to 8th Parts by weight L-Tryptophan 1 to 5 Parts by weight
39 paragraphs, as filed
p0001The present invention relates to aqueous dialysis and rinsing solutions for intraperitoneal administration containing electrolytes in physiological amounts, an amino acid mixture as osmotic substance and optionally other additives.
p0002In patients with acute or chronic renal insufficiency, renal function must be compensated by alternative methods. Such alternative methods are hemodialysis and peritoneal dialysis. In hemodialysis, the blood of the patient is cleaned extracorporeally using an artificial semipermeable membrane. In peritoneal dialysis, the peritoneum acts as a semipermeable membrane. The Dialysier solution is introduced via a catheter into the peritoneal cavity. After a certain equilibration time, ie after konzentrationsabhängigem exchange of substances of the dialysate to the blood, then the Dialysier solution is "consumed" removed from the peritoneal cavity and replaced by a new Dialysier solution. Peritoneal dialysis, for example, continuous ambulatory peritoneal dialysis (CAPD) or intermittent peritoneal dialysis are increasingly gaining in importance. While the majority of uremia caused by manifestation can be well controlled at a long-term peritoneal dialysis, there are a number of metabolic defects that may be associated with the osmotically active substance or the buffer of the dialysate used.
p0003The essential function of a Dialysier solution for renal failure patients is the one hand, to take excess water and harnpflichtige substances, and on the other hand is, substances that metabolically conditioned at low concentrations in the organism occur (electrolyte balance) feed. Moreover, to be achieved through a Peritonealdialysier solution for the patient a positive nutritive effect, which in this regard is particularly important, as the CAPD patient emits a day in the dialysate about 5 to 12 grams of protein and some amino acids g.
p0004The most common glucose was used as osmotically active substance so far. Thus, all commercially available Peritonealdialysier solutions contain glucose as the osmotically active substance in order to ensure an appropriate ultrafiltration. However, glucose shows some disadvantages. absorb CAPD patients per day 150 to 300 g glucose from the dialysate. This amount corresponds to approximately one third of the daily caloric requirement and contributes to obesity in. Especially in diabetic patients hyperglycaemia are described with increased insulin requirements. This is especially evident in the intermittent peritoneal dialysis. Hyperglycaemia lead further to hyperlipidemia, which atherosclerotic changes can be caused as a result. From peritoneal glucose is rapidly absorbed, thereby reducing the osmotic gradient between peritoneal dialysis solution and plasma decreased. This in turn is associated with a reduction of ultrafiltration. A further disadvantage of glucose is that it represents an excellent substrate for many microorganisms and thereby the development of a microbial peritonitis is favored.
p0005In order to eliminate these disadvantages and problems associated with the use of glucose as the osmotically active substance in Dialysier solutions, many investigations have been made for alternative osmotic substances. It has already been proposed for some time to use amino acid solutions in place of glucose as the osmotically active substances (see FIG. Lancet, Vol. 2, 1968, page 812).
p0006According to the PCT patent application WO 82/03773 a Dialysier solution is proposed, containing an aqueous solution of physiological salts for osmotic compatibility with the blood sufficient concentration, a mixture of physiological amino acids and insulin in an amount sufficient for the patient a significant assimilation the amino acids thereto. As an example of a suitable amino acid mixture is disclosed in PCT patent application, the commercial product Travasol, which may be contained in the Dialysier solution in amounts of from 1 to 4 g per liter, called. Preferably the Dialysier solutions included under this patent application nor glucose in amounts of 0.5 to 4 g per liter. The addition of insulin to Dialysier solution to both the metabolism of glucose and the amino acids and the assimilation of the amino acids in the cells be facilitated.
p0007Although the problems of hyperglycaemia by these Dialysier solutions mitigated or avoided and reaches appropriate osmotic effects, however, it is with these known amino acid-containing solutions Dialysier not possible to achieve a sufficient nutritional effect in patients with renal failure.
p0008Therefore, there is still a considerable need for osmotically effective Dialysier solutions that can be administered for long periods to patients without attributable complications or microbial complications occur to osmotic phenomena, the sufficient removal of water and uremic substances, a correction ensure the electrolyte balance and an effective nutritive effect in patients with renal failure.
p0009Object of the present invention is therefore to provide osmotically effective dialysis and rinsing solutions available that can be administered over a long period of patient intraperitoneally without occur on osmotic He phenomena attributable complications, and the previously known dialysis rinsing solutions occurring microbial and peritoneal dialytic complications are avoided, a sufficient removal of water and urinary metabolites and correction of electrolyte balance be ensured as well as for the patient by the Dialysier solution an effective nutritive contribution will be ensured.
p0010This object was achieved by a dialysis and rinsing solution having as osmotically active substance is an amino acid mixture, which contains the following amino acids in the following relative amounts, expressed in parts by weight: <tables id="tabl0001" num="0001"><table frame="all"><tgroup cols="5" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="31.50mm" /><colspec colnum="2" colname="col2" colwidth="31.50mm" /><colspec colnum="3" colname="col3" colwidth="31.50mm" /><colspec colnum="4" colname="col4" colwidth="31.50mm" /><colspec colnum="5" colname="col5" colwidth="31.50mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">L-histidine</entry><entry namest="col2" nameend="col2" align="char" char=",">4</entry><entry namest="col3" nameend="col3" align="left">to</entry><entry namest="col4" nameend="col4" align="char" char=",">6</entry><entry namest="col5" nameend="col5" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-isoleucine</entry><entry namest="col2" nameend="col2" align="char" char=",">6</entry><entry namest="col3" nameend="col3" align="left">to</entry><entry namest="col4" nameend="col4" align="char" char=",">9</entry><entry namest="col5" nameend="col5" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-leucine</entry><entry namest="col2" nameend="col2" align="char" char=",">9</entry><entry namest="col3" nameend="col3" align="left">to</entry><entry namest="col4" nameend="col4" align="char" char=",">13.5</entry><entry namest="col5" nameend="col5" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-methionine</entry><entry namest="col2" nameend="col2" align="char" char=",">9</entry><entry namest="col3" nameend="col3" align="left">to</entry><entry namest="col4" nameend="col4" align="char" char=",">12</entry><entry namest="col5" nameend="col5" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-valine</entry><entry namest="col2" nameend="col2" align="char" char=",">13.5</entry><entry namest="col3" nameend="col3" align="left">to</entry><entry namest="col4" nameend="col4" align="char" char=",">20.5</entry><entry namest="col5" nameend="col5" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-lysine hydrochloride</entry><entry namest="col2" nameend="col2" align="char" char=",">6.5</entry><entry namest="col3" nameend="col3" align="left">to</entry><entry namest="col4" nameend="col4" align="char" char=",">10</entry><entry namest="col5" nameend="col5" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-phenylalanine</entry><entry namest="col2" nameend="col2" align="char" char=",">6</entry><entry namest="col3" nameend="col3" align="left">to</entry><entry namest="col4" nameend="col4" align="char" char=",">9.5</entry><entry namest="col5" nameend="col5" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-threonine</entry><entry namest="col2" nameend="col2" align="char" char=",">6.5</entry><entry namest="col3" nameend="col3" align="left">to</entry><entry namest="col4" nameend="col4" align="char" char=",">10</entry><entry namest="col5" nameend="col5" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-tyrosine</entry><entry namest="col2" nameend="col2" align="char" char=",">7.5</entry><entry namest="col3" nameend="col3" align="left">to</entry><entry namest="col4" nameend="col4" align="char" char=",">12</entry><entry namest="col5" nameend="col5" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-Taurine</entry><entry namest="col2" nameend="col2" align="char" char=",">2</entry><entry namest="col3" nameend="col3" align="left">to</entry><entry namest="col4" nameend="col4" align="char" char=",">8th</entry><entry namest="col5" nameend="col5" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-Tryptophan</entry><entry namest="col2" nameend="col2" align="char" char=",">1</entry><entry namest="col3" nameend="col3" align="left">to</entry><entry namest="col4" nameend="col4" align="char" char=",">5</entry><entry namest="col5" nameend="col5" align="left">Parts by weight.</entry></row></tbody></tgroup></table></tables>
p0011Preferably, the amino acid mixture used in this invention has the following amino acids in the following relative amounts, expressed in parts by weight, of: <tables id="tabl0002" num="0002"><table frame="all"><tgroup cols="5" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="31.50mm" /><colspec colnum="2" colname="col2" colwidth="31.50mm" /><colspec colnum="3" colname="col3" colwidth="31.50mm" /><colspec colnum="4" colname="col4" colwidth="31.50mm" /><colspec colnum="5" colname="col5" colwidth="31.50mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">L-histidine</entry><entry namest="col2" nameend="col2" align="char" char=",">4.5</entry><entry namest="col3" nameend="col3" align="left">to</entry><entry namest="col4" nameend="col4" align="char" char=",">5</entry><entry namest="col5" nameend="col5" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-isoleucine</entry><entry namest="col2" nameend="col2" align="char" char=",">6</entry><entry namest="col3" nameend="col3" align="left">to</entry><entry namest="col4" nameend="col4" align="char" char=",">6.5</entry><entry namest="col5" nameend="col5" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-leucine</entry><entry namest="col2" nameend="col2" align="char" char=",">9</entry><entry namest="col3" nameend="col3" align="left">to</entry><entry namest="col4" nameend="col4" align="char" char=",">10</entry><entry namest="col5" nameend="col5" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-methionine</entry><entry namest="col2" nameend="col2" align="char" char=",">9</entry><entry namest="col3" nameend="col3" align="left">to</entry><entry namest="col4" nameend="col4" align="char" char=",">10</entry><entry namest="col5" nameend="col5" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-valine</entry><entry namest="col2" nameend="col2" align="char" char=",">13.5</entry><entry namest="col3" nameend="col3" align="left">to</entry><entry namest="col4" nameend="col4" align="char" char=",">15</entry><entry namest="col5" nameend="col5" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-lysine hydrochloride</entry><entry namest="col2" nameend="col2" align="char" char=",">6.5</entry><entry namest="col3" nameend="col3" align="left">to</entry><entry namest="col4" nameend="col4" align="char" char=",">8th</entry><entry namest="col5" nameend="col5" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-phenylalanine</entry><entry namest="col2" nameend="col2" align="char" char=",">6</entry><entry namest="col3" nameend="col3" align="left">to</entry><entry namest="col4" nameend="col4" align="char" char=",">6.8</entry><entry namest="col5" nameend="col5" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-threonine</entry><entry namest="col2" nameend="col2" align="char" char=",">6.5</entry><entry namest="col3" nameend="col3" align="left">to</entry><entry namest="col4" nameend="col4" align="char" char=",">7</entry><entry namest="col5" nameend="col5" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-tyrosine</entry><entry namest="col2" nameend="col2" align="char" char=",">7.5</entry><entry namest="col3" nameend="col3" align="left">to</entry><entry namest="col4" nameend="col4" align="char" char=",">8.5</entry><entry namest="col5" nameend="col5" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-Taurine</entry><entry namest="col2" nameend="col2" align="char" char=",">4.5</entry><entry namest="col3" nameend="col3" align="left">to</entry><entry namest="col4" nameend="col4" align="char" char=",">6</entry><entry namest="col5" nameend="col5" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-Tryptophan</entry><entry namest="col2" nameend="col2" align="char" char=",">2</entry><entry namest="col3" nameend="col3" align="left">to</entry><entry namest="col4" nameend="col4" align="char" char=",">3</entry><entry namest="col5" nameend="col5" align="left">Parts by weight.</entry></row></tbody></tgroup></table></tables>
p0012Particularly preferred is a mixture of amino acids containing the amino acids in the following relative amounts: <tables id="tabl0003" num="0003"><table frame="all"><tgroup cols="3" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="52.50mm" /><colspec colnum="2" colname="col2" colwidth="52.50mm" /><colspec colnum="3" colname="col3" colwidth="52.50mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">L-histidine</entry><entry namest="col2" nameend="col2" align="right">4.9</entry><entry namest="col3" nameend="col3" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-isoleucine</entry><entry namest="col2" nameend="col2" align="right">6.0</entry><entry namest="col3" nameend="col3" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-leucine</entry><entry namest="col2" nameend="col2" align="right">9.0</entry><entry namest="col3" nameend="col3" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-methionine</entry><entry namest="col2" nameend="col2" align="right">9.0</entry><entry namest="col3" nameend="col3" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-valine</entry><entry namest="col2" nameend="col2" align="right">13.5</entry><entry namest="col3" nameend="col3" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-lysine hydrochloride</entry><entry namest="col2" nameend="col2" align="right">6.5</entry><entry namest="col3" nameend="col3" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-phenylalanine</entry><entry namest="col2" nameend="col2" align="right">6.0</entry><entry namest="col3" nameend="col3" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-threonine</entry><entry namest="col2" nameend="col2" align="right">6.5</entry><entry namest="col3" nameend="col3" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-tyrosine</entry><entry namest="col2" nameend="col2" align="right">7.5</entry><entry namest="col3" nameend="col3" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-Taurine</entry><entry namest="col2" nameend="col2" align="right">4.9</entry><entry namest="col3" nameend="col3" align="left">Parts by weight</entry></row><row><entry namest="col1" nameend="col1" align="left">L-Tryptophan</entry><entry namest="col2" nameend="col2" align="right">2.5.</entry><entry namest="col3" nameend="col3" align="left">Parts by weight.</entry></row></tbody></tgroup></table></tables>
p0013When the amino acid mixtures employed in this invention, it is essential that certain ratios of isoleucine: leucine: valine are respected. Thus, this ratio should be such that isoleucine <leucine <valine. Preferably, the ratio isoleucine: leucine: valine 1: 1.5: 2.15 to 2.25 by weight and is in particular 1: 1.5: 2.25.
p0014Similarly, the ratio of tyrosine: phenylalanine> 1 be. Preferably it should be 1.05 to 1.30: 1 and especially 1.25: 1.
p0015The amino acid mixture used in this invention is used in the dialysis and rinsing solutions of the invention in an amount of 2.0 to 50.0 g amino acid mixture per liter. Preferably, the inventive dialysis and rinsing solutions containing 7.5 to 20 g amino acids per liter and in particular 7.5 to 12.5 g amino acid mixture / l, for example, 10 g amino acid mixture per liter.
p0016The present inventors have surprisingly found that it is possible using the above-mentioned amino acid mixture, to make an effective nutritional contribution in the treatment of patients with renal failure. The composition of the present invention applied amino acid mixture is adjusted to the needs of patients with renal failure. The basis for the composition of the amino acid mixture according to the invention not the plasma amino acid pattern, but the amino acid pattern of intracellular relevant amino acid pools (muscle).
p0017According to a preferred embodiment of the invention dialysis and rinsing solutions contain one or more carboxylic acids in the form of their salts, for example the sodium, potassium or calcium salts. is used Examples of suitable salts are the succinate, fumarate, malate, oxaloacetate, and the like. Preferably malate.
p0018These acids or their salts are present in the inventive solutions in amounts of 2 to 12 g / l, preferably in an amount of 6.53 g / l.
p0019Examples of electrolyte additives for dialysis and rinsing solutions of the invention are sodium, potassium, calcium or magnesium ion-containing electrolytes. The electrolyte salts may be present according to the invention in a known manner in the form of the acetate, lactate, chloride and / or bicarbonate. The ion concentrations in the dialysis and rinsing solutions of the invention are advantageously 125 to 150, in particular 132-140 mmol / l Na +; 0-8, insbesondee 0 to 4 mmol / l K⁺; 0 to 3, especially 0.5 to 2 mmol / l Ca⁺⁺; 0 to 2.5, in particular 0.3 to 1 mmol / l Mg⁺⁺; 10 to 60, in particular 30 to 50 mmol / l ions selected from the group of lactate, acetate and bicarbonate ions and residual Cl⁻.
p0020The dialysis according to the invention and rinse solutions may also contain other suitable physiologically acceptable additives which are added in the form of solutions or emulsions, the solutions of the invention. Examples of such additives are vitamins, water-soluble carbohydrates, protein metabolism influencing hormones, fatty acids and / or fats, glycerol, glycerides and optionally suitable emulsifiers. These additives may be used according to the invention in amounts such as are common in pharmacology.
p0021Examples of vitamins are water-soluble and fat-soluble vitamins such as vitamins A, D, E, B₁, B₂, B₆ and B₁₂, vitamin K, vitamin C, niacin, pantothenic acid, biotin and folic acid. vitamins of the vitamin B group, such as vitamin B₁, B₂ and B₆, pantothenic acid, niacin, biotin and vitamin C. The vitamins are used preferably may be used in a mixture or individually. The dialysis according to the invention and rinse solutions contain vitamins usually in an amount of 10 to 500 mg / l, preferably in an amount of 100 to 200 mg / l, for example in an amount of 150 mg / l.
p0022Examples of water-soluble carbohydrates are monosaccharides such as glucose, fructose, galactose, and sugar alcohols such as sorbitol or xylitol. The carbohydrates can be used singly or in admixture. Preferably, glucose is used. The novel solutions may contain carbohydrates in an amount of 0 to 10 wt .-%, preferably in an amount of 0 to 5 wt .-%, for example, 1 wt .-% contained.
p0023Examples of protein metabolism influencing hormones are androstanolone or nortestosterone. The hormones may be employed individually or in admixture. In the mixtures according to the invention, these hormones can be generally present in a pharmacologically effective amount.
p0024Examples of suitable fatty acids are fatty acids having 5 to 24 carbon atoms. Examples of suitable fats are unsaturated fats such as soybean oil, cotton seed oil or fish oil.
p0025For example, soybean lecithin or purified lecithin from egg According to the invention in general, the fats in the form of emulsions using a suitable emulsifier, such as lecithins, eg. Employed. The fats and / or fatty acids and glycerol or glycerides, 0 to 200 g / l are employed in the solutions according to the invention in amounts of from 0 to 300 g / l, preferably.
p0026The pH of the solutions according to the invention is in the acidic range, preferably in the range of 5.5 to 6.5 and is for example 5.6.
p0027The osmotic pressure of the dialysis solutions according to the invention and rinsing is suitably from 300 to 700 mosm / l, preferably 320-550 mosm / l and especially 350 to 500 mosm / l.
p0028The preparation of the dialysis invention and rinse solutions can to de done n known for producing dialysis and rinsing solutions process. For example, the preparation be such as is described in PCT patent application WO 82/03773. For example, can be done in the case of the additional use of carbohydrates sterilization in a two-compartment bag, wherein the carbohydrate solution (eg., Glucose solution) and in the other chamber, the amino acid solution is in a chamber with the other ingredients, and can after sterilization while maintaining the sterile conditions a compound of the chambers with each other, the two separately prepared and sterilized solutions can be mixed.
p0029The dialysis invention and rinsing solutions are excellent for peritoneal administration. They are highly effective (adequate removal of water and urinary metabolites and appropriate correction of electrolyte balance) and can be administered without the hitherto known for Dialysier solutions microbial and peritonealdialytischen complications occur over longer periods. By dialysis and rinsing solutions of the invention are hyperglycemia, obesity, lack of appetite, hyperlipidemia, particularly in diabetic patients, avoided. The ultrafiltration maximum is reached much earlier than in the prior art, containing glucose as the osmotically active substance Dialysier solutions through the solutions of the invention, making them particularly well suited for rapid drainage. By inventive solutions effective nutritive contribution to Nierenisuffizienten ensures beyond. The daily amino acid loss is corrected by these means and thus stimulates protein synthesis, thus a general improvement of the patient status will be ensured.
p0030The following examples serve to further illustrate the present invention:
Example 1:
p0031a) In one liter of water of injection quality a solution of the following amino acids is produced: <tables id="tabl0004" num="0004"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">L-histidine</entry><entry namest="col2" nameend="col2" align="right">4.9 g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">L-isoleucine</entry><entry namest="col2" nameend="col2" align="right">6.0 g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">L-leucine</entry><entry namest="col2" nameend="col2" align="right">9.0 g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">L-methionine</entry><entry namest="col2" nameend="col2" align="right">9.0 g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">L-valine</entry><entry namest="col2" nameend="col2" align="right">13.5 g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">L-lysine hydrochloride</entry><entry namest="col2" nameend="col2" align="right">6.5 g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">L-phenylalanine</entry><entry namest="col2" nameend="col2" align="right">6.0 g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">L-threonine</entry><entry namest="col2" nameend="col2" align="right">6.5 g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">L-tyrosine</entry><entry namest="col2" nameend="col2" align="right">7.5 g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">L-Taurine</entry><entry namest="col2" nameend="col2" align="right">4.9 g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">L-Tryptophan</entry><entry namest="col2" nameend="col2" align="right">2.5 g / l.</entry></row></tbody></tgroup></table></tables> This solution was diluted to a final concentration of 10 g / l amino acids. b) Using the solution described above, a dialysis invention and rinsing solution was prepared. This solution contained in a liter of water of injection quality, the following ingredients:<tables id="tabl0005" num="0005"><table frame="all"><tgroup cols="3" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="52.50mm" /><colspec colnum="2" colname="col2" colwidth="52.50mm" /><colspec colnum="3" colname="col3" colwidth="52.50mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Amino acid mixture in accordance with a)</entry><entry namest="col2" nameend="col2" align="char" char=",">10</entry><entry namest="col3" nameend="col3" align="left">g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">L-malic acid</entry><entry namest="col2" nameend="col2" align="char" char=",">6.53</entry><entry namest="col3" nameend="col3" align="left">g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">NaCL</entry><entry namest="col2" nameend="col2" align="char" char=",">5,785</entry><entry namest="col3" nameend="col3" align="left">g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">CaCl₂x2H₂O</entry><entry namest="col2" nameend="col2" align="char" char=",">.2573</entry><entry namest="col3" nameend="col3" align="left">g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">MgCl₂x6H₂O</entry><entry namest="col2" nameend="col2" align="char" char=",">.1017</entry><entry namest="col3" nameend="col3" align="left">g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">Na-lactate, 50% solution</entry><entry namest="col2" nameend="col2" align="char" char=",">10.76</entry><entry namest="col3" nameend="col3" align="left">g / l (48 mmol / l)</entry></row><row><entry namest="col1" nameend="col1" align="left">glucose</entry><entry namest="col2" nameend="col2" align="char" char=",">10.0</entry><entry namest="col3" nameend="col3" align="left">g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">Pyridoxine HCL</entry><entry namest="col2" nameend="col2" align="char" char=",">40.0</entry><entry namest="col3" nameend="col3" align="left">mg / l</entry></row><row><entry namest="col1" nameend="col1" align="left">Riboflavin-5-phosphate</entry><entry namest="col2" nameend="col2" align="char" char=",">2.5</entry><entry namest="col3" nameend="col3" align="left">mg / l</entry></row><row><entry namest="col1" nameend="col1" align="left">nicotinamide</entry><entry namest="col2" nameend="col2" align="char" char=",">60</entry><entry namest="col3" nameend="col3" align="left">mg / l</entry></row><row><entry namest="col1" nameend="col1" align="left">thiamin</entry><entry namest="col2" nameend="col2" align="char" char=",">10</entry><entry namest="col3" nameend="col3" align="left">mg / l</entry></row></tbody></tgroup></table></tables> The theoretical osmotic pressure of this solution thus prepared was 500 mOsm / l; pH: 5.6.
Example 2:
p0032Example 1 was repeated with the exception that the amino acid mixture was a) of Example 1 used in accordance with an amount of 7.5 g / l.
Example 3:
p0033Example 1 was repeated with the exception that the amino acid mixture was a) of Example 1 was used according to in an amount of 12.5 g / l.
Example 4:
p0034A dialysis invention and rinsing solution was prepared from the ingredients listed below: <tables id="tabl0006" num="0006"><table frame="all"><tgroup cols="3" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="52.50mm" /><colspec colnum="2" colname="col2" colwidth="52.50mm" /><colspec colnum="3" colname="col3" colwidth="52.50mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Na⁺</entry><entry namest="col2" nameend="col2" align="char" char=",">134.0</entry><entry namest="col3" nameend="col3" align="left">mmol / l</entry></row><row><entry namest="col1" nameend="col1" align="left">Ca⁺⁺</entry><entry namest="col2" nameend="col2" align="char" char=",">1.75</entry><entry namest="col3" nameend="col3" align="left">mmol / l</entry></row><row><entry namest="col1" nameend="col1" align="left">Mg⁺⁺</entry><entry namest="col2" nameend="col2" align="char" char=",">0.50</entry><entry namest="col3" nameend="col3" align="left">mmol / l</entry></row><row><entry namest="col1" nameend="col1" align="left">Cl⁻</entry><entry namest="col2" nameend="col3" align="center">correspondingly</entry></row><row><entry namest="col1" nameend="col1" align="left">lactate</entry><entry namest="col2" nameend="col2" align="char" char=",">48</entry><entry namest="col3" nameend="col3" align="left">mmol / l</entry></row><row><entry namest="col1" nameend="col1" align="left">L-Histidon</entry><entry namest="col2" nameend="col2" align="char" char=",">0.6</entry><entry namest="col3" nameend="col3" align="left">g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">L-isoleucine</entry><entry namest="col2" nameend="col2" align="char" char=",">0.8</entry><entry namest="col3" nameend="col3" align="left">g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">L-leucine</entry><entry namest="col2" nameend="col2" align="char" char=",">1.2</entry><entry namest="col3" nameend="col3" align="left">g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">L-methionine</entry><entry namest="col2" nameend="col2" align="char" char=",">1.2</entry><entry namest="col3" nameend="col3" align="left">g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">L-valine</entry><entry namest="col2" nameend="col2" align="char" char=",">1.80</entry><entry namest="col3" nameend="col3" align="left">g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">L-lysine hydrochloride</entry><entry namest="col2" nameend="col2" align="char" char=",">0.85</entry><entry namest="col3" nameend="col3" align="left">g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">L-phenylalanine</entry><entry namest="col2" nameend="col2" align="char" char=",">0.8</entry><entry namest="col3" nameend="col3" align="left">g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">L-threonine</entry><entry namest="col2" nameend="col2" align="char" char=",">0.85</entry><entry namest="col3" nameend="col3" align="left">g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">L-tyrosine</entry><entry namest="col2" nameend="col2" align="char" char=",">1.0</entry><entry namest="col3" nameend="col3" align="left">g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">L-Taurine</entry><entry namest="col2" nameend="col2" align="char" char=",">0.65</entry><entry namest="col3" nameend="col3" align="left">g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">L-Tryptophan</entry><entry namest="col2" nameend="col2" align="char" char=",">0.3</entry><entry namest="col3" nameend="col3" align="left">g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">L-malic acid</entry><entry namest="col2" nameend="col2" align="char" char=",">6.5</entry><entry namest="col3" nameend="col3" align="left">g / l</entry></row><row><entry namest="col1" nameend="col1" align="left">pyridoxine</entry><entry namest="col2" nameend="col2" align="char" char=",">40</entry><entry namest="col3" nameend="col3" align="left">mg / l</entry></row><row><entry namest="col1" nameend="col1" align="left">Riboflavin-5-phosphate</entry><entry namest="col2" nameend="col2" align="char" char=",">2.5</entry><entry namest="col3" nameend="col3" align="left">mg / l</entry></row><row><entry namest="col1" nameend="col1" align="left">nicotinamide</entry><entry namest="col2" nameend="col2" align="char" char=",">60</entry><entry namest="col3" nameend="col3" align="left">mg / l</entry></row><row><entry namest="col1" nameend="col1" align="left">thiamin</entry><entry namest="col2" nameend="col2" align="char" char=",">10</entry><entry namest="col3" nameend="col3" align="left">mg / l</entry></row><row><entry namest="col1" nameend="col1" align="left">pantothenic acid</entry><entry namest="col2" nameend="col2" align="char" char=",">10</entry><entry namest="col3" nameend="col3" align="left">mg / l</entry></row><row><entry namest="col1" nameend="col1" align="left">ascorbic acid</entry><entry namest="col2" nameend="col2" align="char" char=",">35</entry><entry namest="col3" nameend="col3" align="left">mg / l</entry></row><row><entry namest="col1" nameend="col1" align="left">biotin</entry><entry namest="col2" nameend="col2" align="char" char=",">0.1</entry><entry namest="col3" nameend="col3" align="left">mg / l</entry></row></tbody></tgroup></table></tables>
p0035The theoretical osmotic pressure of the solution was 500 mOsm / l; pH: 5.6.
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| Document | Relation | Office | Cited during |
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| WO9513061A1 | Cited by | World Intellectual Property Organization (WIPO) | International search |
| EP2177225A1 | Cited by | European Patent Office (EPO) | Search report |
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| CN1128615C | Cited by | China | Search report |
| US7208479B2 | Cited by | United States of America | Applicant |
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7 members in 4 offices; this record represents the family
Priority claims2
| Document | Office | Kind | Date |
|---|---|---|---|
| 3821043 | Germany | – | |
| 3821043 | Germany | A |
Members7
| Document | Office | Kind | |
|---|---|---|---|
| EP0347714A2This record | European Patent Office (EPO) | A2 | |
| DE3821043A1 | Germany | A1 | |
| AU3663689A | Australia | A | |
| JPH0253723A | Japan | A | |
| EP0347714A3 | European Patent Office (EPO) | A3 | |
| AU615553B2 | Australia | B2 | |
| DE3821043C2 | Germany | C2 |
9 legal events, as the office reported them to INPADOC
Over the term
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| Event | Code | |
|---|---|---|
| Application refused18R | 18R | |
| Information on the status of an ep patent application or granted ep patentGrantedSTATUS: THE APPLICATION HAS BEEN REFUSEDSTAA | STAA | |
| First examination report despatched17Q | 17Q | |
| Request for examination filed17P | 17P | |
| Designated contracting statesAK | AK | |
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Numbers
- Publication
- 0347714
- Application
- 891106502
Titles3
- German
- Dialysier- und Spül-Lösung zur intraperitonealen Verabreichung
- English
- Dialysing and rinsing solution for intraperitoneal dispensing
- French
- Solution de dialyse et de rinçage pour l'administration par voie péritonéale
Classification
- CPC, 5
- A61M1/287
- A61K31/195
- A61K38/01
- A61P3/00
- A61P3/12
- IPC, 7
- A61K9 08
- A61K31 195
- A61K31 198
- A61K38 01
- A61M1 28
- A61P3 00
- A61P3 12
Designated states11
- Contracting states, 11
- Austria
- Belgium
- Switzerland
- Germany
- Spain
- France
- United Kingdom
- Italy
- Liechtenstein
- Netherlands (Kingdom of the)
- Sweden