GB2300121A

GB2300121A - Complete infusion set with thioctic acid solution

Info

Publication number: GB2300121A
Application number: GB9608214A
Authority: GB
Inventors: Heinz Ulrich; Reinhard Muckenschnabel; Michael Lobisch; Robert Hermann
Original assignee: Asta Medica GmbH
Current assignee: Asta Medica GmbH
Priority date: 1995-04-25
Filing date: 1996-04-19
Publication date: 1996-10-30
Anticipated expiration: 2016-04-19
Also published as: ITTO960094V0; PT102071A; PT102071B; ES2125800B1; BE1009699A6; PT9273T; ITTO960331A1; IT1285056B1; ES2125800A1; AT1314U1; GB9608214D0; NL1002937C2; FR2733428B3; ITTO960094U3; NL1002937A1; ITTO960331A0; ITTO960331A3; DE29506604U1; FR2733428A1; GB2300121B

Abstract

A complete infusion set for parenteral use comprises a preconstituted infusion and an infusion set wherein the infusion consists of thioctic acid of a concentration of 5 to 50 mg/ml and a water-soluble salt former thereof to establish a pH of 5 to 10, together with further auxiliary substances and optionally solubilising agents in preconstituted infusion or injection containers having a volume of 10 to 500 ml, and the infusion set consists of a drip chamber, tube with roller clamp, reducing piece, cone with protective cap and butterfly cannula, wherein the tube and cannula have small diameter. The infusion preferably contains trometamol as the water-soluble salt with a molar ratio of thioctic acid to trometamol of 1:1.1 to 1:3.2. It is useful in the treatment of paraethesia in diabetic polyneuropathy.

Description

Complete infusion set This invention relates to a complete infusion set for the parenteral administration of infusion solutions, in particular of pharmaceutical preparations for infusion/injection therapy.

Infusion arrangements and dosage forms for parenteral use are known.

These are preferably offered for sale as ampoules, alone or in combination with an infusion set.

Such developments are also known for thioctic acid.

These are preferably single substance preparations of racemic thioctic acid, but may also be of the pure enantiomers or also combinations with other pharmaceutically active substances or vitamins, amino acids, endogenous cofactors and trace elements.

4, 10, 24 ml ampoules for infusion use or multi-component infusion solutions are, for example, known.

These combination packs consist of a pharmaceutical concentrate (thioctic acid ampoules) , plus a carrier solution (for example bottles containing physiological saline), plus an infusion set, plus a syringe for drawing up.

These known arrangements in conjunction with the dosage forms have various disadvantages.

Thus, two or more preparation stages are usually required, such as mixing the solution and setting the infusion rate.

The possibility of contamination increases in line with the number of preparation stages.

The standard diameters of the cannulas and the tube material result in very variable infusion times.

Solutions of thioctic acid in particular have for decades been administered in a conventional ampoule form, although parenteral therapy with thioctic acid is assuming great significance in medical practice.

The ampoules have hitherto been injected slowly in undiluted form, sometimes with special metering devices, or the ampoules have been diluted with sodium chloride solution and injected.

The auxiliaries used in the ampoules for stabilisation and sterilisation sometimes led to tissue irritation at the injection site.

The object of the innovation is to develop a highly compatible preconstituted infusion solution which is stable in storage with an administration unit, consisting of a pharmaceutically stable infusion product and an infusion set adapted thereto.

This object is achieved by the provision of a preconstituted infusion and a special infusion set associated with the product.

The preconstituted solution consists of a water-soluble salt of thioctic acid, preferably the trometamol salt.

The molar ratio of thioctic acid to trometamol is 1:1.1 to 1:3.2, preferably 1:1.4 to 1:2.8.

Other or two or more organic and inorganic (for example alkali metal salts) salt formers may also be used in a freely selectable molar ratio.

When ethylenediamine is used as the salt former, the molar ratio of thioctic acid:ethylenediamine may be 1:0.8 to 1:2.

Other or two or more salt formers may be used in order to establish the pH.

The solution is adjusted with the salt former to a pH value in the range from 5 to 10, advantageously to a pH value of 7.5 to 9, preferably of 8.5.

The concentration of the solution is in the range from 5 to 50 mg of thioctic acid per ml, preferably from 8 to 14 mg per ml, but preferably 12 mg per ml.

In absolute terms, the quantity of thioctic acid used is 20 to 2000 mg, preferably 600 mg per filling.

Further auxiliary substances may be used in accordance with the rules of pharmaceutical science for stabilisation and sterilisation, for example solubilising agents, such as propylene glycol.

The preconstituted infusion is preferably a virtually isotonic solution without a solubilising agent.

The volume of a preconstituted infusion should be below 300 ml, preferably below 100 ml, in order to reduce the patient's NaCl intake.

The solution may be already preconstituted, but it may, however, also be mixed in the container shortly before use from the solid pharmaceutical active and auxiliary substances and added liquid.

The preconstituted infusion is packaged in containers for preconstituted infusions or in injection bottles, the volume of which may be between 10 and 500 ml, preferably in preconstituted infusion or injection bottles having a volume of 50 ml.

Containers which may be used are made from white glass or coloured glasses, advantageously from brown glass for protection from light, but containers made from suitable, optionally coloured plastic materials may also be used, all of which containers have only a small headspace above the solution.

The containers may be sealed in a sterile and air-tight manner with various grades of bungs.

A transparent or coloured bag is used for hanging.

Creating the described preconstituted infusion was surprising as it is neither routine nor obvious for the person skilled in the art to achieve this in practice. It would have been obvious to introduce 600 mg of active ingredient into 250 ml of physiological sodium chloride solution, as was conventional practice when using ampoules.

This solution did not, however, achieve the goal because, unexpectedly, there is a narrow range of active ingredient concentrations for parenteral dosage forms of thioctic acid, outside which pharmaceutically stable dosage forms cannot be obtained.

The special infusion set associated with the product consists of a drip chamber comprising the sub-units or assemblies, bottom part, injection port, upper part, vent flap, bacterial filter, protective cap and a 15 4m filter.

To this is connected a tube enclosed by a roller clamp comprising a housing and wheel, to which is connected a butterfly via a reducing piece and a cone with a protective cap.

A small internal diameter of the tube and of the butterfly cannula, conveniently of some 0.3 mm, prevents too much of the solution containing thioctic acid from being infused at once. The roller clamp may be used to reduce the quantity of solution, but never to increase it.

By virtue of the specific geometry of the tube and of the associated butterfly, which throttles flow, this special infusion set ensures, without adjustment, a constant, compatible infusion time of at least 12 minutes, relative to a liquid throughput of 50 ml.

The duration of infusion may also be extended to more than 30 minutes.

The complete infusion set contains, in addition to the preconstituted infusion, the special infusion set. All the component parts may be provided with sterile packaging, individually or advantageously together. The individual component parts may also be partially or completely connected together or integrated functionally into a single product.

The complete infusion set may be combined in packs of 1 to 500 units per outer pack, preferably in single, 5 unit and 10 unit outer packs.

This complete infusion set according to the invention may be used for the treatment of paraesthesia in diabetic polyneuropathy.

In comparison with the prior art in the form of ampoules for infusion use or combination packs, the complete infusion set has practical advantages.

- NaCl intake is reduced, - improved local compatibility by dispensing with propylene glycol, so rendering the solution isotonic, - shortening of administration time by elimination of preparation stages, such as drawing up in a syringe, mixing and setting the drip rate, - increased safety of use due to fixed infusion times and reduced possibility of contamination, - reduction of waste, such as sodium chloride bottles, ampoules, syringes for drawing up, - oxidation sensitivity of active material overcome by minimising the free volume and thus the oxygen content in the headspace of the container.

Practical example Figure 1 is intended to illustrate the embodiment of the special infusion set.

The set consists of a drip chamber 1, consisting of the subassemblies bottom part injection port upper part vent flap bacterial filter protective cap 15 4m filter.

The tube attached hereto, which is enclosed by a roller clamp comprising a housing and wheel, leads, via a reducing piece and a cone with a protective cap, to a 25 G butterfly 2. A bottle hanger 3 holds the preconstituted infusion or injection bottle and receives the drip chamber.

Using the bottle hanger, an injection bottle is set at a height of 1 m between the level of liquid in the bottle and the connection to the patient and connected to the set.

The 50 ml of solution in the injection bottle containing 50 ml of injection solution with the constituents 952.3 mg of the trometamol salt of thioctic acid, corresponding to 600 mg of thioctic acid, together with the remaining constituents trometamol, sodium chloride and water for injection, flow through the infusion device in 12 minutes.

Claims

1. Complete infusion set for parenteral use comprising a preconstituted infusion and an infusion set, characterised by - a preconstituted infusion consisting of thioctic acid of a concentration of 5 to 50 mg/ml and a water-soluble salt former thereof, with a salt former establishing a pH value of 5 to 10, together with further auxiliary substances and optionally solubilising agents in preconstituted infusion or injection containers having a volume of 10 to 500 ml, together with - a special infusion set consisting of a drip chamber, tube with roller clamp, reducing piece, cone with protective cap and butterfly cannula, wherein the tube and butterfly cannula have a small diameter.

2. Complete infusion set according to claim 1, characterised by trometamol as the water-soluble salt former, wherein the molar ratio of thioctic acid to trometamol is 1:1.1 to 1:3.2, preferably 1:1.4 to 1:2.8.

3. Complete infusion set according to claims 1 and 2, characterised by other or two or more organic or inorganic salt formers in a freely selectable molar ratio.

4. Complete infusion set according to claim 1, characterised by a pH value established with other or two or more salt formers of 7.5 to 9, preferably of

8.5.

5. Complete infusion set according to claim 1, characterised by a preconstituted infusion with a thioctic acid concentration of 8 to 14 mg/ml, preferably of 12 mg/ml.

6. Complete infusion set according to claims 1 to 5, characterised by an isotonic solution of the preconstituted infusion without a solubilising agent.

7. Complete infusion set according to claims 1 to 6, characterised by a volume of the preconstituted infusion of less than 300 ml, preferably of less than 100 ml, preferably of 50 ml.

8. Complete infusion set according to claims 1 to 7, characterised by the coloured, preferably brown coloured, containers containing the preconstituted infusion.

9. Complete infusion set according to claims 1 to 8, characterised by a sterile-packed set, partially or completely connected together and comprising a preconstituted infusion and special infusion set.

10. Complete infusion set for parenteral use comprising a preconstituted infusion and an infusion set substantially as hereinbefore described with reference to the example.