Catheter lubricating gel with increased stability

Description

[0001] The invention relates to a gel composition for topical medical use as a lubricant, in particular as a catheter lubricant. The gel composition contains an antiseptic and preferably also an anesthetic.

[0002] Some medical procedures require the insertion of medical devices such as catheters, endoscopes, probes, or other medical equipment into a patient's body orifice, such as the urethra. These procedures are generally uncomfortable or even painful for the patient, and injuries to the orifice in question are possible. To minimize discomfort, prevent injuries, and generally simplify these procedures, it is common practice to instill a lubricant into the orifice in question or, if necessary, to apply it to the devices before they are inserted into the orifice. Hydrogels, among others, are used for this purpose. These may be drug-free or may contain local anesthetics such as lidocaine and antiseptics such as chlorhexidine.

[0003] However, stability issues can arise with such lubricants. For example, active ingredients can degrade over time. For example, chlorhexidine, although suitable for a variety of purposes, can, under certain conditions, form the harmful 4-chloroaniline as a degradation product. Furthermore, antiseptics can interact with active ingredients such as local anesthetics or at least reduce their solubility in the gel. For example, chlorhexidine interacts with some salts such as lidocaine hydrochloride in a way that significantly reduces the solubility product of these substances and leads to undesirable precipitation reactions. While reactive antiseptics such as chlorhexidine can be replaced with other antiseptics, such as parabens, this usually comes at the expense of effectiveness and also tolerability or safety.

[0004] Catheter lubricants containing lidocaine, chlorhexidine, and butylene glycol are known in the prior art from WO 2006 / 099259 A2. WO 2015 / 074730 A1 and WO 2020 / 136502 A1 also describe catheter lubricants containing dissolved local anesthetics and antiseptics.

[0005] The object of the invention is to provide a generic galenic gel composition containing an antiseptic and preferably also an anesthetic, in which the aforementioned undesirable effects are reduced and whose stability and shelf life are consequently improved. The aim is to significantly increase the performance and safety of corresponding products compared to the prior art.

[0006] Against this background, the invention relates to a gel composition comprising an antiseptic and preferably further an anesthetic, wherein the gel composition further contains a diol component which is hexylene glycol, pentylene glycol or structural isomers thereof.

[0007] Presumably due to its chemical structure and surface-active properties, the diol component as defined above leads to improved solubility of the anesthetic and antiseptic, and to increased stability of the active ingredients as well as the physicochemical properties of the galenic gel composition. This effect could not be achieved with other, particularly low-chain polyols such as glycerol or propylene glycol.

[0008] The gel composition is preferably a hydrogel. Polyalcohols of natural or synthetic origin, for example, can be used as gel-forming hydrophilic polymers. Preferred examples include cellulose derivatives such as hydroxyethylcellulose.

[0009] The water content (excluding dissolved ingredients) typically accounts for 40-99% of the total mass of the hydrogel. The content of gel-forming polymers, measured in relation to the total mass of the moist gel composition, is preferably between 0.1 wt% and 5 wt%, more preferably between 0.5 wt% and 3 wt%.

[0010] The anesthetic is preferably a topical local anesthetic of the ester or aminoamide type. Examples include benzocaine, procaine, and tetracaine (all ester types) or lidocaine, prilocaine, etidocaine, ropivacaine, mepivacaine, and bupivacaine (all amide types). A particularly preferred example includes lidocaine.

[0011] The content of anesthetic measured in relation to the total mass of the moist gel composition is preferably between 0.1 wt% and 7 wt%, more preferably between 0.5 wt% and 5 wt%.

[0012] The antiseptic is preferably a guanidine derivative, especially a biguanide compound. Examples include chlorhexidine, polyhexanide, or hexamidine. Chlorhexidine is particularly preferred.

[0013] The content of antiseptic measured in relation to the total mass of the moist gel composition is preferably between 0.01 and 4 wt%, preferably between 0.02 and 2 wt%, more preferably between 0.03 and 1 wt%.

[0014] According to the invention, the diol component is hexylene glycol, pentylene glycol, and structurally isomeric alkanediols of these compounds. Hexylene glycol is particularly preferred.

[0015] The content of the diol component measured in relation to the total mass of the moist gel composition is preferably between 5 wt% and 50 wt%, more preferably between 10 wt% and 30 wt%.

[0016] Preferably, the antiseptic and, if present, the anesthetic in the gel composition are present mainly as salts of a hydroxycarboxylic acid in the gel composition.

[0017] The hydroxycarboxylic acid can be an α-hydroxycarboxylic acid, with carbon numbers of less than six being preferred. Examples include glycolic acid or lactic acid. Lactic acid is particularly preferred. The acid can be present in the gel composition partly as a salt and, in particular, as a mixture of salt and free acid, thus acting as a buffer component.

[0018] Until now, pH adjustment with hydrochloric acid has been common practice in generic gel compositions. However, the introduction of additional chloride ions, or generally inorganic ions such as phosphate ions, potentially results in the formation of poorly soluble salts with the antiseptic. In this case, the active ingredients can be added as a free base and form salts with the hydroxycarboxylic acid in the composition. The content of inorganic ions should be reduced as much as possible. However, a small amount can be tolerated as long as the hydroxycarboxylic acid is present in sufficient concentration.

[0019] Preferably, the gel composition comprises less than 1.5 wt.%, more preferably less than 1.0 wt.% chloride or generally inorganic anions.

[0020] The content of hydroxycarboxylic acid measured in relation to the total mass of the moist gel composition is preferably between 0.01 wt% and 10 wt%, more preferably between 0.5 wt% and 5 wt%.

[0021] The pH of the gel composition is preferably adjusted by a buffer formed partially or entirely from the hydroxycarboxylic acid and a salt of the hydroxycarboxylic acid (where the cation may be at least partially the antiseptic or, if present, anesthetic). Examples include lactate buffers, glycolate buffers, or combinations thereof.

[0022] The pH of the gel composition is preferably in a range of pH 3 to pH 8, preferably between pH 4 and pH 7. Deviating pH values ​​favor precipitation reactions of the components, particularly antiseptics or anesthetics. Furthermore, the natural pH in the urogenital tract is approximately pH 4 to pH 7, whereby optimal tolerability is ensured for corresponding applications within these ranges.

[0023] In the gel composition according to the invention, the active ingredients, in particular the antiseptic and any anesthetic present, are preferably present in solution. In other words, it is preferred that no emulsion particles or solid carrier particles carrying or containing the active ingredients are present in the gel composition. The invention therefore preferably relates to a single-phase system. The possibility of providing a stable composition as a solution is facilitated by the diol component.

[0024] The invention further relates to the use of a gel composition according to the invention for instillation into body orifices, in particular into the urethra, or for application to areas of medical devices whose intended use includes introduction into a body orifice, in particular the urethra, rectum, or bronchial space, or use in the insertion of a suprapubic catheter. Use as a catheter lubricant is particularly preferred.

[0025] Further details and advantages of the invention will become apparent from the embodiment described below.

[0026] A catheter lubricant is manufactured with the ingredients listed in Table 1. Table 1: Composition raw material g / 100g Water [g] 70,22 Chlorhexidine*2HCl [g] 0,05 Na-Lactate solution 50% [g] 6,00 Lidocaine [g] free base 1,73 HEC [g] 2,00 Hexylene glycol [g] 20,00 LacAc 90% [g] qs NaOH [ml] qs Total amount of solution 100

[0027] A similar catheter lubricant with a different buffer, with lidocaine as hydrochloride and, in particular, without hexylene glycol, is state of the art and is marketed by Pharmazeutische Fabrik Montavit Ges.mbH under the trade name Cathejell Lidocain C.

[0028] In the composition described above, it was surprisingly observed that hexylene glycol has a positive influence on the shelf life and stability of the gel composition. In particular, the solubility of chlorhexidine can be significantly increased. One possible explanation is that the higher glycols, especially those with a carbon number of four, are suitable as solubilizers due to their nonpolar carbon chain and polar hydroxyl groups. Furthermore, these substances have good tissue compatibility and, in appropriate concentrations, skin-care properties. The use of lidocaine as the free base also prevents the introduction of chloride ions, which prevents the formation of poorly soluble chlorhexidine crystals.

Claims

1. Gel composition comprising an antiseptic agent and preferably also an anaesthetic agent, characterised in that the gel composition further contains a diol component, which is hexylene glycol, pentylene glycol or structural isomers.

2. Gel composition according to claim 1, characterised in that the gel composition is a hydrogel, the water content of which is preferably between 40 and 99 wt.%.

3. Gel composition according to any of the preceding claims, characterised in that the anaesthetic agent is a topical local anaesthetic of the ester type or the amino-amide type, in particular the amino-amide type, and is particularly preferably lidocaine.

4. Gel composition according to any of the preceding claims, characterised in that the content of anaesthetic agent, measured on the basis of the total mass of the moist gel composition, is between 0.1 wt.% and 7 wt.%, preferably between 0.5 wt.% and 5 wt.%.

5. Gel composition according to any of the preceding claims, characterised in that the antiseptic agent is a guanidine derivative, preferably chlorhexidine, polyhexanide or hexamidine, and particularly preferably chlorhexidine.

6. Gel composition according to any of the preceding claims, characterised in that the content of anaesthetic agent, measured on the basis of the total mass of the moist gel composition, is between 0.01 and 4 wt.%, preferably between 0.02 and 2 wt. %, more preferably between 0.03 and 1 wt.%.

7. Gel composition according to any of the preceding claims, characterised in that the content of the diol component, measured on the basis of the total mass of the moist gel composition, is between 5 wt.% and 50 wt.%, preferably between 10 wt.% and 30 wt.%.

8. Gel composition according to any of the preceding claims, characterised in that the antiseptic agent and, if provided, the anaesthetic agent are mainly present as salts of a hydroxycarboxylic acid in the gel composition.

9. Gel composition according to claim 8, characterised in that the hydroxycarboxylic acid is an ?-hydroxycarboxylic acid, preferably an ?-hydroxycarboxylic acid having less than six carbon atoms, and particularly preferably is glycolic acid or lactic acid.

10. Gel composition according to any of the preceding claims, characterised in that the gel composition comprises less than 1.5 wt.%, preferably less than 1.0 wt.%, chloride and preferably generally inorganic anions.

11. Gel composition according to any of the preceding claims, characterised in that the pH of the gel composition is pH 3 to pH 8, preferably pH 4 to pH 7.

12. Gel composition according to any of the preceding claims, characterised in that the antiseptic agent and the potentially provided anaesthetic agent are present in a form dissolved in the gel composition.

13. Gel composition according to any of the preceding claims for use for instilling in body orifices, in particular in the urethra, or for application to regions of medical devices, the intended use of which involves insertion into a body orifice, in particular the urethra, the rectum or the bronchial system, or for use when inserting a suprapubic catheter.

14. Gel composition according to any of claims 1-12 for use according to claim 13, characterised in that the gel composition is used as a catheter lubricant gel.