NL1002937C2 - Ready-to-use infusion set. - Google Patents

Description

Title: Finished infusion set Description

The invention relates to a finished infusion set for parenteral administration of infusion solutions, in particular of thioctic acid-containing finished drugs for infusion / injection therapy.

Infusion setups and administration forms for parenteral use are already known. These are preferably presented as ampoules, alone or in combination with infusion accessories.

Such embodiments are also known for thioctic acid. These are preferably monopreparations of racemic thioctic acid, but also those of the pure enantiomers or also combinations with other medicinally active substances or vitamins, amino acids, endogenous cofactors and trace elements.

For example, ampoules for 4 ml, 10 ml, 24 ml infusion application or multi-component infusion solutions are known. These combination packs consist of a drug concentrate (thioctic acid ampoules) plus carrier solution (eg bottles with physiological table salt solution) plus infusion set plus pull-up syringe.

These known arrangements associated with the dosage forms present several drawbacks. This usually requires several steps, such as mixing the solution and setting the infusion rate. The number of steps also increases the possibilities for contamination. Standard diameters for the cannulas and tubing material lead to infusion times that are very variable.

Especially the administration of solutions of thioctic acid has been taking place for decades via a conventional ampoule form, although parenteral therapy with thioctic acid has an important place in medical practice.

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To date, the ampoules have been injected undiluted and slowly, partly with special dispensers, or the ampoules have been diluted and injected with sodium chloride solution.

The stabilizing or sterilizing excipients used in the ampoules could lead to tissue irritations at the insertion site.

The aim of the innovation is the development of a storage-stable and well-tolerated finished infusion solution with administration unit, consisting of a galenically stable infusion product and an appropriate infusion set.

The object is solved by providing a ready infusion and a special infusion set associated with the product.

The finished infusion solution consists of a water-soluble salt of thioctic acid, preferably the tromethamine salt. The molar ratio of thioctic acid to tromethamine is 1: 1.1 to 1: 3.2, preferably 1: 1.4 to 1: 2.8.

Other or more organic and inorganic (e.g. alkali metal salts) salt former can also be used in a free molar ratio.

When using ethylenediamine as a salt former, the 25 mol ratio of thioctic acid: ethylenediamine can be 1: 0.8 to 1: 2.

Other or more salt formers can be added to adjust the pH. The solution with the salt former is adjusted to a pH value in the range from 5 to 10, preferably to a pH value from 7.5 to 9, most preferably 8.5.

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

The absolute amount of thioctic acid used is 20 to 2000 mg, preferably 600 mg per filling.

Further auxiliary substances according to the rules of galenic science for stabilization and sterilization 1002937 3 can be used, as well as substances that must promote solution, such as propylene glycol. Preferably, the finished infusion is a substantially isotonic solution without substances to promote solution.

The volume of a ready infusion should be below 300 ml, preferably below 100 ml, to reduce the burden on the patient with NaCl.

The solution can already be made ready for use, but it can also only be prepared in the container from the solid galenic active substances and auxiliary substances and added liquid shortly before application.

The finished infusion is filled into containers for finished infusion resp. in injection bottles, the volumes of which can be between 10 and 500 ml, preferably in 15 finished infusion or injection bottles with a volume of 50 ml.

Containers of white glass or of colored glass, preferably of brown glass for protection against light, can also be used, but holders of suitable, optionally colored plastic materials, all of which have only a little free space above the solution . The containers can be closed sterile and airtight with various qualities of stoppers. A transparent or colored bag is used for the suspension.

The provision of the described finished infusion was surprising because the realization for the skilled person is not trivial and obvious in practice. Obvious would have been the introduction of 600 mg of active ingredient into 250 ml of physiological sodium chloride-30 solution, as in the practice of using ampoules. However, this solution was unsuccessful because, unexpectedly, in parenteral forms of administration of thioctic acid, there is a narrow range for the concentration of the active substance beyond which galenically stable forms of administration cannot be realized.

The special infusion assembly associated with the product consists of a drip chamber formed of the construction groups and resp. construction parts lower part, cast ring, 1002937 4 upper part, aeration valve, bacteria filter, protective cap and a filter of 15 μπι. A hose connects to this with a roller clamp formed from the housing and the wheel, which comprises the hose, to which a butterfly connects via a reducing piece and a cone with protective cap.

A small internal diameter of the tubing and wing cannula, which is preferably 0.3 mm, prevents too much thioctic acid solution from being infused at one time. With the roller clamp less solution can be set, but never again.

Due to the special geometry of the hoses and the associated butterfly valve acting as flow limiter, this special infusion set ensures a constant infusion time even without adjustment of at least 15 12 minutes, based on a liquid flow of 50 ml.

The infusion time can also be extended beyond 30 minutes.

The finished infusion set contains, in addition to the finished infusion, the special infusion set. All ingredients may be included separately, but preferably they are packaged together sterile. The individual components can also be partially or completely ready to be joined together or functionally integrated into a single product.

The finished infusion set may be subdivided in the range of 1 to 500 units per outer package, preferably in 1st, 5th and 10th outer packages.

This finished infusion set according to the invention can be used for the therapy of sensory disturbances in diabetic polyneuropathy.

The finished infusion set has advantages over the prior art in use in the form of ampoules for infusion use, respectively. combination packaging. The NaCl load is reduced, the local tolerance is improved by refraining from propylene glycol and thereby isotonization, the useful life is shortened by the elimination of steps, as evidenced by the pull-up of the syringe, mixing and setting of the dripping speed, 1002937 5 the reliability of use is increased by fixed infusion times and smaller contamination possibilities, waste, such as sodium chloride bottles, ampoules, pull-up syringes, is avoided, 5 - the oxidation sensitivity of the active substance is solved by minimizing the free volume and thus the oxygen content in the head space of the container .

10 Implementation example

The implementation of the special infusion set is illustrated with reference to a drawing in Figure 1.

The assembly consists of a drip chamber l, consisting of the assemblies 15 · bottom part • molded ring • top part • aeration valve • bacteria filter 20 · protective cap • filter of 15 μπι.

The connecting hose with a roller clamp formed from the housing and the wheel, which comprises this hose, leads via a reducer piece to a cone with protective cap, to which a 25 G 25 butterfly 2 connects. A bottle hanger 3 serves to receive the finished infusion or injection bottle and to pass through the drip chamber.

By means of bottle hangers, an injection bottle is fixed at 1 m between the liquid level of the bottle and the connection to the patient at 1 m and connected to the assembly.

The 50 ml solution flows continuously from the injection bottle with 50 ml of the injection solution containing the components 952.3 mg of the thromic acid tromethamine salt, which corresponds to 600 mg of thioctic acid, and the further 35 components of tromethamine, sodium chloride and water for injection purposes. in 12 min through the infusion equipment.

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Claims (9)

1. Ready-to-use parenteral infusion set consisting of a ready infusion and an infusion set, characterized by: a ready infusion consisting of thioctic acid in the concentration of 5 to 50 mg / ml and its water-soluble salt former, with a pH value from 5 to 10 adjusting salt former, as well as further excipients and optionally substances that promote solution, in containers for finished infusion or finished injection with volumes of 10 to 10 500 ml, and a special infusion set consisting of drip chamber, hose with roller clamp , reducer, cone with protective cap and wing cannula exists, with hose and wing cannula having a small diameter. Finished infusion set according to claim 1, characterized by tromethamine as a water-soluble salt former, wherein the molar ratio of thioctic acid to tromethamine is 1: 1.1 to 1: 3.2, preferably 1: 1.4 to 1: 2.8 . Finished infusion set according to claims 1 and 2, characterized by other or more organic or inorganic salt formers in a free molar ratio. Finished infusion set according to claim 1, characterized by a pH value of 7.5 to 9, preferably 8.5, adjusted with other or more salt formers. Finished infusion set according to claim 1, characterized by a ready infusion with a thioctic acid concentration of 8 to 14 mg / ml, preferably 12 mg / ml. Finished infusion set according to claims 1 to 30, characterized by an isotonic solution of the finished infusion without substances to promote solution. Finished infusion set according to claims 1 to 6, characterized by a volume of the finished infusion of 1002937 less than 300 ml, preferably less than 100 ml, most preferably 50 ml. Finished infusion set according to claims 1 to 7, characterized by the finished infusion containing 5 colored, preferably brown colored, containers. Ready-to-use infusion set according to claims 1 to 8, characterized by a sterile packaged set consisting of a ready-made infusion and a special infusion set, partially or completely connected. 1002937