1. Patent Search
  2. Details

SYRINGE AND KIT FOR INTRAVESICAL USE

20210308308 · 2021-10-07

    Inventors

    Cpc classification

    International classification

    Abstract

    The present invention relates to a method for producing a sterile oxybutynin-comprising composition in a preferably ready-to-use piston syringe or for producing a preferably ready-to-use sterile piston syringe filled with an oxybutynin-comprising composition as well as a sterile oxybutynin-comprising composition and piston syringe as such.

    Claims

    1. A method for producing a sterile oxybutynin-comprising composition in a ready-to-use piston syringe filled with the oxybutynin-comprising composition, wherein the piston syringe comprises a syringe body in the form of a syringe cylinder, on the one hand, and a syringe piston with a piston plug, on the other hand, wherein the syringe body is formed from a cycloolefin-(co)polymer and wherein the piston plug is formed from a halobutyl rubber; wherein the method comprises the following steps: a) filling the piston syringe with the oxybutynin-comprising composition and providing the oxybutynin-comprising composition in the piston syringe, wherein the oxybutynin is used in the form of the hydrochloride, wherein the oxybutynin-comprising composition is configured as an aqueous composition and wherein the oxybutynin-comprising composition comprises, in combination and in each case in pharmaceutically effective amounts: oxybutynin hydrochloride in a concentration of (1±0.5) mg/ml and sodium chloride, calculated as sodium, in a concentration of (3.5±0.5) mg/ml, wherein the oxybutynin-comprising composition is adjusted to a pH value in the range of from 3 to 5; and subsequently: b) performing a vapor sterilization of the oxybutynin-comprising composition in the piston syringe and of the piston syringe filled with the oxybutynin-comprising composition.

    2. The method according to claim 1, wherein the oxybutynin-comprising composition comprises the oxybutynin hydrochloride in a concentration of (1±0.1) mg/ml; wherein the oxybutynin-comprising composition comprises the sodium chloride, calculated as sodium, in a concentration of (3.5±0.1) mg/ml; wherein the pH value of the oxybutynin-comprising composition is adjusted using hydrochloric acid.

    3. The method according to claim 1, wherein vapor sterilization is carried out as a steam sterilization for a duration in the range of from 1 min to 500 min at temperatures in the range of from 105° C. to 160° C. and under pressurization at an absolute pressure in the range of from 1.1 bar to 10 bar in the presence of an atmosphere comprising a mixture of steam with at least one gas selected among inert gases, oxygen, air and mixtures thereof in a closed autoclave apparatus.

    4. The method according to claim 1, wherein vapor sterilization is carried out under overkill conditions at about 121° C. and for a duration of at least 15 min.

    5. The method according to claim 1, wherein vapor sterilization is carried out according to the conditions of Pharmacopoea Europaea (Ph. Eur.), Chapter 5.1.1, Edition 07/2017: 50101, under overkill conditions and at about 121° C. and for a duration of at least 15 min.

    6. The method according to claim 1, wherein the piston syringe filled with the oxybutynin-comprising composition has been inserted, prior to the performance of the vapor sterilization, into a packaging closed or sealed in a water-proof and germ-proof manner, wherein at least part of the packaging is configured to be steam-permeable, wherein the packaging is also sterilized when the vapor sterilization is performed.

    7. The method according to claim 1, wherein a plurality of piston syringes filled with the oxybutynin-comprising composition is sterilized simultaneously, wherein during the performance of the vapor sterilization said plurality of piston syringes are brought together on a syringe carrier.

    8. The method according to claim 1, wherein the sterile oxybutynin-comprising composition obtained after vapor sterilization and the sterile piston syringe filled with the oxybutynin-comprising composition obtained after vapor sterilization have a SAL (Sterility Assurance Level) value of at least 10.sup.−5.

    9. The method according to claim 1, wherein the sterile oxybutynin-comprising composition obtained after vapor sterilization comprises a content of oxybutynin degradation products of at most 5% by weight, based on oxybutynin hydrochloride.

    10. A method for producing a sterile oxybutynin-comprising composition in a ready-to-use piston syringe filled with the oxybutynin-comprising composition, wherein the piston syringe comprises a syringe body in the form of a syringe cylinder, on the one hand, and a syringe piston with a piston plug, on the other hand, wherein the syringe body is formed from a cycloolefin-(co)polymer and wherein the piston plug is formed from a halobutyl rubber; wherein the method comprises the following steps: a) filling the piston syringe with the oxybutynin-comprising composition and providing the oxybutynin-comprising composition in the piston syringe, wherein the oxybutynin is used in the form of the hydrochloride, the oxybutynin-comprising composition is configured as an aqueous composition and the oxybutynin-comprising composition comprises, in combination and in each case in pharmaceutically effective amounts: oxybutynin hydrochloride (oxybutynin-HCl) in a concentration of about 1 mg/ml and sodium chloride, calculated as sodium, in a concentration of about wherein the oxybutynin-comprising composition is adjusted to a pH value in the range of from 3.8 to 4.5; and subsequently: b) performing a vapor sterilization as a steam sterilization of the oxybutynin-comprising composition in the piston syringe and of the piston syringe filled with the oxybutynin-comprising composition, wherein the vapor sterilization is carried out under overkill conditions and at about 121° C. and for a duration of at least 15 min under the conditions of Pharmacopoea Europaea (Ph. Eur.), Chapter 5.1.1, Edition 07/2017: 50101.

    11. A sterile oxybutynin-comprising composition to be used in the treatment of a neurogenic bladder dysfunction of a human patient, wherein the oxybutynin-comprising composition is obtained by a method according to claim 1.

    12. A sterile oxybutynin-comprising composition to be used in the treatment of a neurogenic bladder dysfunction of a human patient, wherein the oxybutynin-comprising composition is present in a ready-to-use piston syringe, wherein the piston syringe comprises a syringe body in the form of a syringe cylinder, on the one hand, and a syringe piston with a piston plug, on the other hand, wherein the syringe body is formed from a cycloolefin-(co)polymer and wherein the piston plug is formed from a halobutyl rubber; wherein the oxybutynin-comprising composition comprises the oxybutynin in the form of the hydrochloride, wherein the oxybutynin-comprising composition is configured as an aqueous composition and wherein the oxybutynin-comprising composition comprises, in combination and in each case in pharmaceutically effective amounts: oxybutynin hydrochloride in a concentration of (1±0.5) mg/ml and sodium chloride, calculated as sodium, in a concentration of (3.5±0.5) mg/ml, wherein the oxybutynin-comprising composition has a pH value in the range of from 3 to 5; and wherein the oxybutynin-comprising composition comprised in the piston syringe, including the piston syringe, is vapor-sterilized via steam-sterilization.

    13. The composition according to claim 12, wherein the oxybutynin-comprising composition comprises the oxybutynin hydrochloride in a concentration of (1±0.1) mg/ml; wherein the oxybutynin-comprising composition comprises the sodium chloride, calculated as sodium, in a concentration of (3.5±0.1) mg/ml; wherein the pH value of the oxybutynin-comprising composition is adjusted using hydrochloric acid.

    14. The composition according to claim 12, wherein the sterile oxybutynin-comprising composition obtained after vapor sterilization and the sterile piston syringe filled with the oxybutynin-comprising composition obtained after vapor sterilization have a SAL (Sterility Assurance Level) value of at least 10.sup.−5.

    15. The composition according to claim 12, wherein the sterile oxybutynin-comprising composition obtained after vapor sterilization comprises a content of oxybutynin degradation products of at most 5% by weight, based on oxybutynin hydrochloride.

    16. The composition according to claim 12, wherein the sterile oxybutynin-comprising composition obtained after vapor sterilization comprises a content of oxybutynin degradation products of at most 1% by weight, based on oxybutynin hydrochloride.

    17. A ready-to-use piston syringe, wherein the piston syringe comprises a syringe body in the form of a syringe cylinder, on the one hand, and a syringe piston with a piston plug, on the other hand, wherein the syringe body is formed from a cycloolefin-(co)polymer and wherein the piston plug is formed from a halobutyl rubber; wherein the piston syringe is filled with a sterile oxybutynin-comprising composition, wherein the oxybutynin is used in the form of the hydrochloride, wherein the oxybutynin-comprising composition is configured as an aqueous composition and wherein the oxybutynin-comprising composition comprises, in combination and in each case in pharmaceutically effective amounts: oxybutynin hydrochloride in a concentration of (1±0.5) mg/ml and sodium chloride, calculated as sodium, in a concentration of (3.5±0.5) mg/ml, wherein the oxybutynin-comprising composition is adjusted to a pH value in the range of from 3 to 5; wherein the oxybutynin-comprising composition comprised in the piston syringe, including the piston syringe, has been vapor sterilized by steam-sterilization.

    18. The ready-to-use piston syringe of claim 17, wherein the piston syringe is configured and adapted to be used in the treatment of a neurogenic bladder dysfunction of a human patient.

    19. The ready-to-use piston syringe of claim 17, wherein the piston syringe has a volume in the range of from 4 ml to 25 ml; and wherein the piston syringe comprises the oxybutynin-comprising composition in an amount in the range of from 4 ml to 25 ml.

    20. The ready-to-use piston syringe of claim 17, wherein the piston syringe comprises a first opening for receiving a syringe piston and wherein the piston syringe comprises a syringe piston formed from a polypropylene or from a cycloolefin-(co)polymer, and wherein the piston syringe comprises a second opening for discharging and applying the oxybutynin-comprising composition, wherein the piston syringe comprises a closing cap for closing the second opening, wherein the closing cap is formed from a halobutyl rubber.

    21. The ready-to-use piston syringe of claim 17, wherein vapor sterilization is carried out under overkill conditions and at about 121° C. and for a duration of at least 15 min.

    22. The ready-to-use piston syringe of claim 17, wherein vapor sterilization is carried out under the conditions according to Pharmacopoea Europaea (Ph. Eur.), Chapter 5.1.1, Edition 07/2017: 50101, under overkill conditions and at about 121° C. and for a duration of at least 15 min.

    23. The ready-to-use piston syringe of claim 17, wherein the sterile piston syringe filled with the sterile oxybutynin-comprising composition obtained after vapor sterilization and the oxybutynin-comprising composition obtained after vapor sterilization comprise a Sterility Assurance (SAL) value of at least 10.sup.−5.

    24. A kit comprising an instillation system, with the kit comprising: (i) at least one sterile oxybutynin-comprising composition as defined in claim 12 and present in a ready-to-use piston syringe as defined in claim 17; (ii) at least one instillation device connectable to the piston syringe; and (iii) at least one instillation manual comprising application instructions.

    Description

    [0209] Hereinafter, the present invention will also be described on the basis of a FIGURE elucidation using a preferred embodiment or configuration. In connection with the explanation of this preferred embodiment or configuration of the present invention, which however is in no way restrictive with respect to the present invention, further advantages, properties, aspects and features of the present invention are also shown.

    [0210] The FIGURE representation according to

    [0211] FIG. 1 shows a schematic sectional view of a piston syringe used in the method according to the invention or a piston syringe filled with the sterile oxybutynin-comprising composition as such according to the invention in side view.

    [0212] Especially, FIG. 1 also shows the sterile oxybutynin-comprising composition 1 according to the invention, with which the piston syringe 2 is filled, wherein the piston syringe 2 is especially configured as a disposable piston syringe and wherein the piston syringe 2 comprises a syringe body 2a, especially a syringe cylinder, on the one hand and a syringe piston 2b with a piston plug 3 on the other hand. In this context, the syringe body 2a is formed from a cycloolefin-(co)polymer (COP or COC), and the piston plug 3 is formed from a halobutyl rubber, especially from a chlorobutyl rubber or from a bromobutyl rubber, preferably from a bromobutyl rubber. FIG. 1 shows that the piston syringe 2 is filled with the sterile oxybutynin-comprising composition 1 according to the present invention. FIG. 1 further illustrates that the piston syringe 2 according to the invention comprises a first opening 2c for receiving the syringe piston 2b with the piston plug 3 and that the piston syringe 2 according to the invention also comprises a second opening 2d, especially opposite of the first opening 2c, especially a discharge opening. The second opening 2d is closed with a closing element 4 in the form of a closing cap, wherein the closing element or the closing cap is formed from a halobutyl rubber, especially from a chlorobutyl rubber or from a bromobutyl rubber, preferably from a bromobutyl rubber. FIG. 1 thus shows the closed state of the piston syringe with the oxybutynin-comprising composition therein according to the invention. Within the scope of the method according to the invention, this unit consisting of a sealed piston syringe with the oxybutynin-comprising composition comprised can be vapor sterilized, so that in this way a corresponding sterile oxybutynin-comprising composition or a sterile piston syringe filled with the composition according to the invention is obtained.

    [0213] Further configurations, modifications and variations as well as advantages of the present invention are easily recognizable and realizable for the person skilled in the art reading the description without leaving the scope of the present invention.

    [0214] The following examples are merely intended to illustrate the present invention, but without limiting the present invention to this.

    Exemplary Embodiments

    [0215] The explanations described below show the improved properties of the sterile oxybutynin-comprising composition provided on the basis of the method according to the invention, namely with respect to the improved stability of the composition during sterilization with the reduction of degradation products of oxybutynin hydrochloride.

    [0216] Particularly in the case of terminal vapor sterilization of a composition for instillation into the bladder, which comprises the active ingredient oxybutynin hydrochloride in a concentration of 1 mg/ml at a pH value of the composition of 4.0, and which—in contrast to the present invention—is prefilled in polypropylene syringes with piston plugs made of a conventional rubber material, it behaves in such a way that after the vapor sterilization has been carried out, the oxybutynin content drops to 85 to 90% of the previously present active ingredient content. During vapor sterilization in piston syringes made of polypropylene with piston plugs made of a conventional rubber material the oxybutynin decomposition product phenylcyclohexylglycolic acid is formed, and in such quantities that are a factor of 2 to 3 above the specification limit. In addition, further impurities result in quantities sometimes exceeding 0.5%.

    [0217] Without being bound to any theory, the acid resistance sometimes is—in contrast to the materials used according to the present invention—very low for polypropylene, wherein the high temperatures during vapor sterilization also promote possible reactions between the composition and the syringe material, which can also lead to the formation of further impurities. In this context, the degradation product of oxybutynin hydrochloride in the form of phenylcyclohexylglycolic acid can particularly be produced by two different reactions, namely saponification in alkaline solution on the one hand and hydrolysis in acidic solution on the other hand. Since the pH value of the composition is in the acidic range, it can be assumed—without being bound to this theory—that the degradation product is primarily the result of a hydrolysis of oxybutynin hydrochloride, wherein this reaction is further intensified by the high temperatures present during sterilization. The hydrolysis of the active ingredient results in both a reduction of the active ingredient content and the formation of phenylcyclohexylglycolic acid during vapor sterilization. Furthermore, in contrast to the present invention, the formation of phenylcyclohexylglycolic acid is further enhanced or accelerated as a result of the rubber material normally used for the piston plug. Without limiting this theory, it is generally the case that rubber materials commonly used for piston plugs generally comprise a high proportion of unsaturated C—C double bonds, which results in an increased reactivity of the material. In addition, and without limiting this theory, phenylcyclohexylglycolic acid is more reactive than the active ingredient due to the free acid group, so that phenylcyclohexylglycolic acid formed during sterilization reacts at least partially with the rubber material and is thus removed from the reaction equilibrium, which favors the degradation of the active ingredient.

    [0218] In contrast, the present invention uses piston syringes based on cycloolefin-(co)polymers (COP or COC) and piston plugs or closing caps based on halobutyl rubber, especially chlorobutyl rubber or bromobutyl rubber, preferably bromobutyl rubber, and a respective oxybutynin-comprising composition, a significantly improved stability of the composition is observed with a lower degradation of the active ingredient and thus a reduced formation of degradation products, especially phenylcyclohexylglycolic acid, under defined vapor sterilization. In contrast to polypropylene, the cycloolefin-(co)polymer (COP or COC) used for the piston syringe according to the invention has a high stability even against acidic compositions. In addition, it behaves in relation to the piston plug or the closing cap in such a way that the halobutyl rubber used for this purpose according to the invention comprises a considerably lower number of C—C double bonds and is therefore less reactive than rubber materials normally used. In addition, halobutyl rubber comprises improved heat stability and improved aging properties and low gas permeability.

    [0219] On this basis, within the scope of the present invention, a respective sterile oxybutynin-comprising composition with improved properties can be obtained by vapor sterilization, both with respect to the guarantee of a high sterility and with respect to the guarantee of a high or unchanged active ingredient content, due to a significant reduction of the formation of corresponding degradation products.

    [0220] Overall, it can thus be stated that, on the basis of the method according to the invention, using a special oxybutynin-comprising composition and using a special piston syringe with special components in this respect, an efficient and at the same time gentle vapor sterilization of the underlying composition can be carried out, wherein the degradation of the active ingredient is reduced, so that, in this respect, corresponding stable compositions are also provided.

    [0221] The present invention will be better understood by the following aspects, which form part of the present invention:

    Aspect 1:

    [0222] 1. A method for producing a sterile oxybutynin-comprising composition in a preferably ready-to-use piston syringe, especially a disposable piston syringe, and/or for producing a preferably ready-to-use sterile piston syringe filled with an oxybutynin-comprising composition, especially a disposable piston syringe, [0223] wherein the piston syringe comprises a syringe body, especially a syringe cylinder, on the one hand and a syringe piston with a piston plug on the other hand, wherein the syringe body is formed from a cycloolefin-(co)polymer (COP or COC) and wherein the piston plug is formed from a halobutyl rubber; [0224] wherein the method comprises the following steps: [0225] a) filling the piston syringe with the oxybutynin-comprising composition and/or providing the oxybutynin-comprising composition in the piston syringe, [0226] wherein the oxybutynin is used in the form of the hydrochloride, the oxybutynin-comprising composition is configured as an aqueous composition and the oxybutynin-comprising composition comprises, in combination and in each case in effective, especially pharmaceutically effective, amounts, [0227] oxybutynin hydrochloride (oxybutynin-HCl) in a concentration of (1±0.5) mg/ml and [0228] sodium chloride, calculated as sodium, in a concentration of (3.5±0.5) mg/ml, [0229] wherein the oxybutynin-comprising composition is adjusted to a pH value in the range of from 3 to 5, especially in the range of from 3.8 to 4.5, and/or wherein the oxybutynin-comprising composition comprises a pH value in the range of from 3 to 5, especially in the range of from 3.8 to 4.5; [0230] and subsequently [0231] b) vapor sterilization, especially steam sterilization, of the oxybutynin-comprising composition in the piston syringe and/or of the piston syringe filled with the oxybutynin-comprising composition.

    Aspect 2:

    [0232] 2. The method according to aspect 1, [0233] wherein the oxybutynin-comprising composition comprises the oxybutynin hydrochloride (oxybutynin-HCl) in a concentration of (1±0.4) mg/ml, especially in a concentration of (1±0.3) mg/ml, preferably in a concentration of (1±0.2) mg/ml, preferably in a concentration of (1±0.1) mg/ml, more preferably in a concentration of about 1 mg/ml.

    Aspect 3:

    [0234] 3. The method according to aspect 1 or 2, [0235] wherein the oxybutynin-comprising composition comprises the sodium chloride, calculated as sodium, in a concentration of (3.5±0.4) mg/ml, especially in a concentration of (3.5±0.3) mg/ml, preferably in a concentration of (3.5±0.2) mg/ml, preferably in a concentration of (3.5±0.1) mg/ml, more preferably in a concentration of about 3.5 mg/ml.

    Aspect 4:

    [0236] 4. The method according to any of the preceding aspects, [0237] wherein the pH value of the oxybutynin-comprising composition is adjusted using and/or by means of hydrochloric acid.

    Aspect 5:

    [0238] 5. The method according to any of the preceding aspects, [0239] wherein the piston syringe has a volume, especially a receiving volume for the oxybutynin-comprising composition, in the range of from 4 ml to 25 ml, especially in the range of from 6 ml to 20 ml, preferably in the range of from 8 ml to 15 ml, preferably in the range of from 9 ml to 12 ml, more preferably of about 10 ml; and/or [0240] wherein the piston syringe comprises the oxybutynin-comprising composition in an amount in the range of from 4 ml to 25 ml, especially in the range of from 6 ml to 20 ml, preferably in the range of from 8 ml to 15 ml, preferably in the range of from 9 ml to 12 ml, more preferably of about 10 ml.

    Aspect 6:

    [0241] 6. The method according to any of the preceding aspects, [0242] wherein the piston plug is formed from a chlorobutyl rubber or from a bromobutyl rubber, preferably from a bromobutyl rubber.

    Aspect 7:

    [0243] 7. The method according to any of the preceding aspects, [0244] wherein the piston syringe, especially the syringe cylinder, comprises a first opening, especially for receiving a syringe piston; and/or [0245] wherein the piston syringe comprises a syringe piston, especially wherein the syringe piston is formed from polypropylene or especially wherein the syringe piston is formed from a cycloolefin-(co)polymer (COP or COC).

    Aspect 8:

    [0246] 8. The method according to any of the preceding aspects, [0247] wherein the piston syringe comprises a second opening, especially a discharge opening, preferably for discharging and/or applying the oxybutynin-comprising composition.

    Aspect 9:

    [0248] 9. The method according to any of the preceding aspects, [0249] wherein the piston syringe comprises a closing element, especially a closing cap, preferably for closing the second opening, especially wherein the closing element is formed from a halobutyl rubber, especially from a chlorobutyl rubber or from a bromobutyl rubber, preferably from a bromobutyl rubber.

    Aspect 10:

    [0250] 10. The method according to any of the preceding aspects, [0251] wherein vapor sterilization is carried out under the application of temperature (heating); and/or [0252] wherein vapor sterilization is carried out at temperatures of at least 105° C., especially of at least 110° C., preferably of at least 115° C., preferably of at least 120° C.; and/or [0253] wherein vapor sterilization is carried out at temperatures of at most 160° C., especially of at most 150° C., preferably of at most 140° C., preferably of at most 130° C.; and/or [0254] wherein vapor sterilization is carried out at temperatures in the range of from 105° C. to 160° C., especially in the range of from 110° C. to 150° C., preferably in the range of from 115° C. to 140° C., preferably in the range of from 20° C. to 130° C., more preferably of about 121° C.

    Aspect 11:

    [0255] 11. The method according to any of the preceding aspects, [0256] wherein vapor sterilization is carried out for a duration of at least 1 min, especially of at least 2 min, preferably of at least 3 min, preferably of at least 5 min, more preferably of at least 8 min, most preferably of at least 10 min, even more preferably of at least 15 min, yet even more preferably of at least 17 min; and/or [0257] wherein vapor sterilization is carried out for a duration of at most 500 min, especially of at most 400 min, preferably of at most 200 min, preferably of at most 100 min, more preferably of at most 60 min, most preferably of at most 45 min, even more preferably of at most 30 min, yet even more preferably of at most 25 min; and/or [0258] wherein vapor sterilization is carried out for a duration in the range of from 1 min to 500 min, especially in the range of from 2 min to 400 min, preferably in the range of from 3 min to 200 min, preferably in the range of from 5 min to 100 min, more preferably in the range of from 8 min to 60 min, most preferably in the range of from 10 min to 45 min, even more preferably in the range of from 15 min to 30 min, yet even more preferably in the range of from 17 min to 25 min, yet again more preferably of about 20 min.

    Aspect 12:

    [0259] 12. The method according to any of the preceding aspects, [0260] wherein vapor sterilization is carried out under pressurization.

    Aspect 13:

    [0261] 13. The method according to any of the preceding aspects, [0262] wherein vapor sterilization is carried out at a relative pressure in the range of from 0.1 bar to 10 bar, especially in the range of from 0.5 bar to 5 bar, preferably in the range of from 1 bar to 3.5 bar, preferably in the range of from 1.5 bar to 3 bar; and/or [0263] wherein vapor sterilization is carried out at an absolute pressure in the range of from 1.1 bar to 10 bar, especially in the range of from 1.5 bar to 6 bar, preferably in the range of from 2 bar to 4.5 bar.

    Aspect 14:

    [0264] 14. The method according to any of the preceding aspects, [0265] wherein vapor sterilization is carried out in the presence of an atmosphere comprising especially pure steam and/or as a saturated steam process; or wherein vapor sterilization is carried out in the presence of a steam/gas mixture, especially a mixture of steam with inert gas, especially nitrogen, and/or oxygen, preferably a steam/air mixture.

    Aspect 15:

    [0266] 15. The method according to any of the preceding aspects, [0267] wherein vapor sterilization is carried out in a preferably closed sterilization device, especially in a gas-tightly closed pressure vessel, preferably in an autoclave apparatus (autoclave); [0268] especially wherein the sterilization atmosphere is generated by injecting steam and/or steam/compressed air mixtures, preferably steam/compressed air mixtures, into the sterilization device; and/or [0269] especially wherein the sterilization atmosphere is generated by injection of already premixed steam/compressed air mixtures and/or by separate injections of steam and compressed air into the sterilization device.

    Aspect 16:

    [0270] 16. The method according to any of the preceding aspects, [0271] wherein, during vapor sterilization, steam is generated from distilled and/or demineralized water; and/or [0272] wherein, during vapor sterilization, compressed air is generated from sterile air, especially wherein the air is cleaned and/or sterilized by passing through filters.

    Aspect 17:

    [0273] 17. The method according to any of the preceding aspects, [0274] wherein vapor sterilization is carried out under overkill conditions and/or at about 121° C. and/or for a duration of at least 15 min, especially of at least 20 min, preferably of about 20 min; and/or [0275] wherein vapor sterilization is carried out according to Pharmacopoea Europaea (Ph. Eur.), chapter 5.1.1 (07/2017:50101), especially under overkill conditions and/or at about 121° C. and/or for a duration of at least 15 min, especially of at least 20 min, preferably of about 20 min.

    Aspect 18:

    [0276] 18. The method according to any of the preceding aspects, [0277] wherein vapor sterilization is carried out multi-cyclically, especially wherein at least the final and/or terminal cycle is carried out under at least one of the conditions defined in Aspects 10 to 17 and/or especially wherein at least the final and/or terminal cycle is carried out under overkill conditions and/or at about 121° C. and/or for a duration of at least 15 min, especially of at least 20 min, preferably of about 20 min.

    Aspect 19:

    [0278] 19. The method according to any of the preceding aspects, [0279] wherein the piston syringe filled with the oxybutynin-comprising composition has been inserted, especially prior to the performance of the vapor sterilization, into a packaging, especially a stand-by packaging, which is closed and/or sealed, especially in a water- and/or germ-proof manner, especially wherein at least part of the packaging is configured to be at least steam-permeable, especially steam- and/or gas-permeable, especially wherein the packaging is also sterilized when the vapor sterilization is performed.

    Aspect 20:

    [0280] 20. The method according to any of the preceding aspects, [0281] wherein a plurality of piston syringes filled with the oxybutynin-comprising composition is sterilized simultaneously, especially wherein preferably, during the performance of the vapor sterilization, several piston syringes are brought together on a (syringe) carrier.

    Aspect 21:

    [0282] 21. The method according to any of the preceding aspects, [0283] wherein the sterile oxybutynin-comprising composition obtained after vapor sterilization and/or the sterile piston syringe filled with the oxybutynin-comprising composition obtained after vapor sterilization has a SAL (Sterility Assurance Level) value of at least 105, especially of at least 10.sup.−6, preferably of at least 10.sup.−7.

    Aspect 22:

    [0284] 22. The method according to any of the preceding aspects, [0285] wherein the sterile oxybutynin-comprising composition obtained after vapor sterilization has a content of degradation product(s) of oxybutynin, especially a content of phenylcyclohexylglycolic acid, of at most 10% by weight, especially of at most 7.5% by weight, preferably of at most 5% by weight, preferably of at most 2% by weight, more preferably of at most 1% by weight, based on oxybutynin hydrochloride.

    Aspect 23:

    [0286] 23. A method for producing a sterile oxybutynin-comprising composition in a preferably ready-to-use piston syringe, especially a disposable piston syringe, and/or for producing a preferably ready-to-use, sterile piston syringe filled with an oxybutynin-comprising composition, especially a disposable piston syringe, especially a method according to any of the preceding aspects, [0287] wherein the piston syringe comprises a syringe body, especially a syringe cylinder, on the one hand and a syringe piston with a piston plug on the other hand, wherein the syringe body is formed from a cycloolefin-(co)polymer (COP or COC) and wherein the piston plug is formed from a halobutyl rubber, especially from a chlorobutyl rubber or from a bromobutyl rubber, preferably from a bromobutyl rubber; [0288] wherein the method comprises the following steps: [0289] a) filling the piston syringe with the oxybutynin-comprising composition and/or providing the oxybutynin-comprising composition in the piston syringe, [0290] wherein the oxybutynin is used in the form of the hydrochloride, the oxybutynin-comprising composition is configured as an aqueous composition and the oxybutynin-comprising composition comprises, in combination and in each case in effective, especially pharmaceutically effective, amounts, [0291] oxybutynin hydrochloride (oxybutynin-HCl) in a concentration of (1±0.4) mg/ml, especially in a concentration of (1±0.3) mg/ml, preferably in a concentration of (1±0.2) mg/ml, preferably in a concentration of (1±0.1) mg/ml, more preferably in a concentration of about 1 mg/ml, and [0292] sodium chloride, calculated as sodium, in a concentration of (3.5±0.4) mg/ml, especially in a concentration of (3.5±0.3) mg/ml, preferably in a concentration of (3.5±0.2) mg/ml, preferably in a concentration of (3.5±0.1) mg/ml, more preferably in a concentration of about 3.5 mg/ml, [0293] wherein the oxybutynin-comprising composition is adjusted to a pH value in the range of from 3 to 5, especially in the range of from 3.8 to 4.5, and/or wherein the oxybutynin-comprising composition has a pH value in the range of from 3 to 5, especially in the range of from 3.8 to 4.5; [0294] and subsequently [0295] b) vapor sterilization, especially steam sterilization, of the oxybutynin-comprising composition in the piston syringe and/or of the piston syringe filled with the oxybutynin-comprising composition.

    Aspect 24:

    [0296] 24. A method for producing a sterile oxybutynin-comprising composition in a preferably ready-to-use piston syringe, especially a disposable piston syringe, and/or for producing a preferably ready-to-use sterile piston syringe filled with an oxybutynin-comprising composition, especially a disposable piston syringe, especially a method according to any of the preceding aspects, [0297] wherein the piston syringe comprises a syringe body, especially a syringe cylinder, on the one hand and a syringe piston with a piston plug on the other hand, wherein the syringe body is formed from a cycloolefin-(co)polymer (COP or COC) and wherein the piston plug is formed from a halobutyl rubber, especially from a chlorobutyl rubber or from a bromobutyl rubber, preferably from a bromobutyl rubber; [0298] wherein the method comprises the following steps: [0299] a) filling the piston syringe with the oxybutynin-comprising composition and/or providing the oxybutynin-comprising composition in the piston syringe, [0300] wherein the oxybutynin is used in the form of the hydrochloride, the oxybutynin-comprising composition is configured as an aqueous composition and the oxybutynin-comprising composition comprises, in combination and in each case in effective, especially pharmaceutically effective, amounts, [0301] oxybutynin hydrochloride (oxybutynin-HCl) in a concentration of about 1 mg/ml and [0302] sodium chloride, calculated as sodium, in a concentration of about 3.5 mg/ml, [0303] wherein the oxybutynin-comprising composition is adjusted to a pH value in the range of from 3.8 to 4.5 and/or wherein the oxybutynin-comprising composition has a pH value in the range of from 3.8 to 4.5; [0304] and subsequently [0305] b) vapor sterilization, especially steam sterilization, of the oxybutynin-comprising composition in the piston syringe and/or of the piston syringe filled with the oxybutynin-comprising composition.

    Aspect 25:

    [0306] 25. A method for producing a sterile oxybutynin-comprising composition in a preferably ready-to-use piston syringe, especially a disposable piston syringe, and/or for producing a preferably ready-to-use sterile piston syringe filled with an oxybutynin-comprising composition, especially a disposable piston syringe, especially method according to any of the preceding aspects, [0307] wherein the piston syringe comprises a syringe body, especially a syringe cylinder, on the one hand and a syringe piston with a piston plug on the other hand, wherein the syringe body is formed from a cycloolefin-(co)polymer (COP or COC) and wherein the piston plug is formed from a halobutyl rubber, especially from a chlorobutyl rubber or from a bromobutyl rubber, preferably from a bromobutyl rubber; [0308] wherein the method comprises the following steps: [0309] a) filling the piston syringe with the oxybutynin-comprising composition and/or providing the oxybutynin-comprising composition in the piston syringe, [0310] wherein the oxybutynin is used in the form of the hydrochloride, the oxybutynin-comprising composition is configured as an aqueous composition and the oxybutynin-comprising composition comprises, in combination and in each case in effective, especially pharmaceutically effective, amounts, [0311] oxybutynin hydrochloride (oxybutynin-HCl) in a concentration of about 1 mg/ml and [0312] sodium chloride, calculated as sodium, in a concentration of about 3.5 mg/ml, [0313] wherein the oxybutynin-comprising composition is adjusted to a pH value in the range of from 3.8 to 4.5 and/or wherein the oxybutynin-comprising composition has a pH value in the range of from 3.8 to 4.5; [0314] and subsequently [0315] b) vapor sterilization, especially steam sterilization, of the oxybutynin-comprising composition in the piston syringe and/or of the piston syringe filled with the oxybutynin-comprising composition, [0316] wherein the vapor sterilization is carried out under overkill conditions and/or at about 121° C. and/or for a duration of at least 15 min, especially of at least 20 min, preferably of about 20 min, and/or [0317] wherein the vapor sterilization is carried out according to Pharmacopoea Europaea (Ph. Eur.), chapter 5.1.1 (07/2017:50101), especially under overkill conditions and/or at about 121° C. and/or for a duration of at least 15 min, especially of at least 20 min, preferably of about 20 min.

    Aspect 26:

    [0318] 26. A sterile oxybutynin-comprising composition, especially for use in the prophylactic and/or therapeutic treatment of neurogenic bladder dysfunction, especially neurogenic bladder voiding disorders, preferably neurogenic bladder dysfunction associated with detrusor hyperactivity and/or detrusor sphincter dyssynergy, [0319] wherein the oxybutynin-comprising composition is obtainable by a method according to any of Aspects 1 to 25; and/or [0320] wherein the oxybutynin-comprising composition has been vapor sterilized, especially steam-sterilized, by a method according to any of Aspects 1 to 25.

    Aspect 27:

    [0321] 27. A sterile oxybutynin-comprising composition, especially for use in the prophylactic and/or therapeutic treatment of neurogenic bladder dysfunction, especially neurogenic bladder voiding disorders, preferably neurogenic bladder dysfunction associated with detrusor hyperactivity and/or detrusor sphincter dyssynergy, especially the composition according to aspect 26, [0322] wherein the oxybutynin-comprising composition is present in a preferably ready-to-use piston syringe, especially a disposable piston syringe, [0323] wherein the piston syringe comprises a syringe body, especially a syringe cylinder, on the one hand and a syringe piston with a piston plug on the other hand, wherein the syringe body is formed from a cycloolefin-(co)polymer (COP or COC) and wherein the piston plug is formed from a halobutyl rubber; [0324] wherein the oxybutynin-comprising composition comprises the oxybutynin in the form of the hydrochloride, the oxybutynin-comprising composition is configured as an aqueous composition and the oxybutynin-comprising composition comprises, in combination and in each case in effective, especially pharmaceutically effective, amounts, [0325] oxybutynin hydrochloride (oxybutynin-HCl) in a concentration of (1±0.5) mg/ml and [0326] sodium chloride, calculated as sodium, in a concentration of (3.5±0.5) mg/ml, [0327] wherein the oxybutynin-comprising composition is adjusted to a pH value in the range of from 3 to 5, especially in the range of from 3.8 to 4.5, and/or wherein the oxybutynin-comprising composition has a pH value in the range of from 3 to 5, especially in the range of from 3.8 to 4.5; and [0328] wherein the oxybutynin-comprising composition comprised in the piston syringe, including the piston syringe, is vapor sterilized, especially steam-sterilized.

    Aspect 28:

    [0329] 28. The composition according to aspect 26 or 27, [0330] wherein the oxybutynin-comprising composition comprises the oxybutynin hydrochloride (oxybutynin-HCl) in a concentration of (1±0.4) mg/ml, especially in a concentration of (1±0.3) mg/ml, preferably in a concentration of (1±0.2) mg/ml, preferably in a concentration of (1±0.1) mg/ml, more preferably in a concentration of about 1 mg/ml; and/or [0331] wherein the oxybutynin-comprising composition comprises the sodium chloride, calculated as sodium, in a concentration of (3.5±0.4) mg/ml, especially in a concentration of (3.5±0.3) mg/ml, preferably in a concentration of (3.5±0.2) mg/ml, preferably in a concentration of (3.5±0.1) mg/ml, more preferably in a concentration of about 3.5 mg/ml.

    Aspect 29:

    [0332] 29. The composition according to any of aspects 26 to 28, [0333] wherein the piston plug is formed from a chlorobutyl rubber or from a bromobutyl rubber, preferably from a bromobutyl rubber.

    Aspect 30:

    [0334] 30. The composition according to any of aspects 26 to 29, [0335] wherein the oxybutynin-comprising composition is vapor sterilized under at least one of the conditions defined in Aspects 10 to 18; and/or [0336] wherein the oxybutynin-comprising composition is vapor sterilized under overkill conditions and/or at about 121° C. and/or for a duration of at least 15 min, especially of at least 20 min, preferably of about 20 min; and/or [0337] wherein the oxybutynin-comprising composition is vapor sterilized according to Pharmacopoea Europaea (Ph. Eur.), chapter 5.1.1 (07/2017:50101), especially under overkill conditions and/or at about 121° C. and/or for a duration of at least 15 min, especially of at least 20 min, preferably of about 20 min.

    Aspect 31:

    [0338] 31. The composition according to any of aspects 26 to 30, [0339] wherein the sterile oxybutynin-comprising composition obtained after vapor sterilization and/or the sterile piston syringe filled with the oxybutynin-comprising composition obtained after vapor sterilization has a SAL (Sterility Assurance) value of at least 10.sup.−5, especially of at least 10.sup.−6, preferably of at least 10.sup.−7.

    Aspect 32:

    [0340] 32. The composition according to any of aspects 26 to 31, [0341] wherein the sterile oxybutynin-comprising composition obtained after vapor sterilization has a content of degradation product(s) of oxybutynin, especially a content of phenylcyclohexylglycolic acid, of at most 10% by weight, especially of at most 7.5% by weight, preferably of at most 5% by weight, preferably of at most 2% by weight, more preferably of at most 1% by weight, based on oxybutynin hydrochloride.

    Aspect 33:

    [0342] 33. The composition according to any of aspects 26 to 32, [0343] wherein the neurogenic bladder dysfunctions are associated with and/or characterized by detrusor overactivity and/or detrusor-sphincter dyssynergia, especially overactive detrusor; and/or [0344] herein the neurogenic bladder dysfunctions are associated with or caused by spinal cord injury, especially paraplegia, spina bifida, diabetes, multiple sclerosis, stroke or Parkinson's disease.

    Aspect 34:

    [0345] 34. A sterile oxybutynin-comprising composition, especially for use in the prophylactic and/or therapeutic treatment of neurogenic bladder dysfunction, especially neurogenic voiding disorders, preferably neurogenic bladder dysfunction associated with detrusor hyperactivity and/or detrusor sphincter dyssynergy, especially composition according to any of aspects 26 to 33, [0346] wherein the oxybutynin-comprising composition is present in a preferably ready-to-use piston syringe, especially a disposable piston syringe, [0347] wherein the piston syringe comprises a syringe body, especially a syringe cylinder, on the one hand and a syringe piston with a piston plug on the other hand, wherein the syringe body is formed from a cycloolefin-(co)polymer (COP or COC) and wherein the piston plug is formed from a halobutyl rubber, especially from a chlorobutyl rubber or bromobutyl rubber, preferably from a bromobutyl rubber; [0348] wherein the oxybutynin-comprising composition comprises the oxybutynin in the form of the hydrochloride, the oxybutynin-comprising composition is configured as an aqueous composition and the oxybutynin-comprising composition comprises, in combination and in each case in effective, especially pharmaceutically effective, amounts, [0349] oxybutynin hydrochloride (oxybutynin-HCl) in a concentration of (1±0.4) mg/ml, especially in a concentration of (1±0.3) mg/ml, preferably in a concentration of (1±0.2) mg/ml, preferably in a concentration of (1±0.1) mg/ml, more preferably in a concentration of about 1 mg/ml, and [0350] sodium chloride, calculated as sodium, in a concentration of (3.5±0.4) mg/ml, especially in a concentration of (3.5±0.3) mg/ml, preferably in a concentration of (3.5±0.2) mg/ml, preferably in a concentration of (3.5±0.1) mg/ml, more preferably in a concentration of about 3.5 mg/ml, [0351] wherein the oxybutynin-comprising composition is adjusted to a pH value in the range of from 3 to 5, especially in the range of from 3.8 to 4.5, and/or wherein the oxybutynin-comprising composition has a pH value in the range of from 3 to 5, especially in the range of from 3.8 to 4.5; and [0352] wherein the oxybutynin-comprising composition comprised in the piston syringe, including the piston syringe, is vapor sterilized, especially steam-sterilized.

    Aspect 35:

    [0353] 35. A sterile oxybutynin-comprising composition, especially for use in the prophylactic and/or therapeutic treatment of neurogenic bladder dysfunction, especially neurogenic bladder voiding disorders, preferably neurogenic bladder dysfunction associated with detrusor hyperactivity and/or detrusor sphincter dyssynergy, especially composition according to any of aspects 26 to 34, [0354] wherein the oxybutynin-comprising composition is present in a preferably ready-to-use piston syringe, especially a disposable piston syringe, [0355] wherein the piston syringe comprises a syringe body, especially a syringe cylinder, on the one hand and a syringe piston with a piston plug on the other hand, wherein the syringe body is formed from a cycloolefin-(co)polymer (COP or COC) and wherein the piston plug is formed from a halobutyl rubber, especially from a chlorobutyl rubber or from a bromobutyl rubber, preferably from a bromobutyl rubber; [0356] wherein the oxybutynin-comprising composition comprises the oxybutynin in the form of the hydrochloride, the oxybutynin-comprising composition is configured as an aqueous composition and the oxybutynin-comprising composition comprises, in combination and in each case in effective, especially pharmaceutically effective, amounts, [0357] oxybutynin hydrochloride (oxybutynin-HCl) in a concentration of about 1 mg/ml and [0358] sodium chloride, calculated as sodium, in a concentration of about 3.5 mg/ml, [0359] wherein the oxybutynin-comprising composition is adjusted to a pH value in the range of from 3.8 to 4.5, and/or wherein the oxybutynin-comprising composition has a pH value in the range of from 3.8 to 4.5; and [0360] wherein the oxybutynin-comprising composition comprised in the piston syringe, including the piston syringe, is vapor sterilized, especially steam-sterilized.

    Aspect 36:

    [0361] 36. A sterile oxybutynin-comprising composition, especially for use in the prophylactic and/or therapeutic treatment of neurogenic bladder dysfunction, especially neurogenic bladder voiding disorders, preferably neurogenic bladder dysfunction associated with detrusor hyperactivity and/or detrusor sphincter dyssynergy, especially composition according to any of aspects 26 to 35, [0362] wherein the oxybutynin-comprising composition is present in a preferably ready-to-use piston syringe, especially a disposable piston syringe, [0363] wherein the piston syringe comprises a syringe body, especially a syringe cylinder, on the one hand and a syringe piston with a piston plug on the other hand, wherein the syringe body is formed from a cycloolefin-(co)polymer (COP or COC) and wherein the piston plug is formed from a halobutyl rubber, especially from a chlorobutyl rubber or from a bromobutyl rubber, preferably from a bromobutyl rubber; [0364] wherein the oxybutynin-comprising composition comprises the oxybutynin in the form of the hydrochloride, the oxybutynin-comprising composition is configured as an aqueous composition and the oxybutynin-comprising composition comprises, in combination and in each case in effective, especially pharmaceutically effective, amounts, [0365] oxybutynin hydrochloride (oxybutynin-HCl) in a concentration of about 1 mg/ml and [0366] sodium chloride, calculated as sodium, in a concentration of about 3.5 mg/ml, [0367] wherein the oxybutynin-comprising composition is adjusted to a pH value in the range of from 3.8 to 4.5, and/or wherein the oxybutynin-comprising composition has a pH value in the range of from 3.8 to 4.5; and [0368] wherein the oxybutynin-comprising composition comprised in the piston syringe, including the piston syringe, is vapor sterilized, especially steam-sterilized, [0369] wherein the vapor sterilization is carried out under overkill conditions and/or at about 121° C. and/or for a duration of at least 15 min, especially of at least 20 min, preferably of about 20 min, and/or [0370] wherein the vapor sterilization is carried out according to Pharmacopoea Europaea (Ph. Eur.), chapter 5.1.1 (07/2017:50101), especially under overkill conditions and/or at about 121° C. and/or for a duration of at least 15 min, especially of at least 20 min, preferably of about 20 min.

    Aspect 37:

    [0371] 37. The composition according to any of aspects 26 to 36, [0372] for use in the prophylactic and/or therapeutic treatment of neurogenic bladder dysfunction, especially neurogenic bladder voiding disorders, preferably neurogenic bladder dysfunction associated with detrusor hyperactivity and/or detrusor sphincter dyssynergy, [0373] especially wherein the neurogenic bladder dysfunction is associated with and/or characterized by detrusor overactivity and/or detrusor-sphincter dyssynergia, especially overactive detrusor; and/or [0374] especially wherein the neurogenic bladder dysfunction is associated with or caused by a spinal cord injury, especially paraplegia, spina bifida, diabetes, multiple sclerosis, stroke or Parkinson's disease; and/or [0375] for instillation and/or for preferred topical application into the urogenital region, especially into the bladder; and/or [0376] wherein the oxybutynin-comprising composition is prepared for administration and/or for instillation and/or for preferably topical application into the urogenital tract, especially into the bladder, and/or wherein the oxybutynin-comprising composition is administered by instillation and/or for preferably topical application into the urogenital tract, especially into the bladder.

    Aspect 38:

    [0377] 38. A piston syringe, especially a disposable piston syringe, wherein the piston syringe comprises a syringe body, especially a syringe cylinder, on the one hand and a syringe piston with a piston plug on the other hand, wherein the syringe body is formed from a cycloolefin-(co)polymer (COP or COC) and wherein the piston plug is formed from a halobutyl rubber, [0378] wherein the piston syringe is filled with a sterile oxybutynin-comprising composition, especially for use in the prophylactic and/or therapeutic treatment of neurogenic bladder dysfunction, especially neurogenic bladder voiding disorders, preferably neurogenic bladder dysfunction associated with detrusor hyperactivity and/or detrusor sphincter dyssynergy, especially as defined in any of Aspects 26 to 37, [0379] wherein the piston syringe is obtainable by a method according to any of Aspects 1 to 25; and/or [0380] wherein the oxybutynin-comprising composition comprised in the piston syringe, including the piston syringe, has been vapor sterilized, especially steam-sterilized, by a method according to any of Aspects 1 to 25.

    Aspect 39:

    [0381] 39. A piston syringe, especially a disposable piston syringe, wherein the piston syringe comprises a syringe body, especially a syringe cylinder, on the one hand and a syringe piston with a piston plug on the other hand, wherein the syringe body is formed from a cycloolefin-(co)polymer (COP or COC) and wherein the piston plug is formed from a halobutyl rubber, especially piston syringe according to aspect 38, [0382] wherein the piston syringe is filled with a sterile oxybutynin-comprising composition, especially for use in the prophylactic and/or therapeutic treatment of neurogenic bladder dysfunction, especially neurogenic bladder voiding disorders, preferably neurogenic bladder dysfunction associated with detrusor hyperactivity and/or detrusor sphincter dyssynergia, [0383] wherein the oxybutynin-comprising composition comprises the oxybutynin in the form of the hydrochloride, the oxybutynin-comprising composition is configured as an aqueous composition and the oxybutynin-comprising composition comprises, in combination and each in effective, especially pharmaceutically effective, amounts, [0384] oxybutynin hydrochloride (oxybutynin-HCl) in a concentration of (1±0.5) mg/ml and [0385] sodium chloride, calculated as sodium, in a concentration of (3.5±0.5) mg/ml, [0386] wherein the oxybutynin-comprising composition is adjusted to a pH value in the range of from 3 to 5, especially in the range of from 3.8 to 4.5, and/or wherein the oxybutynin-comprising composition has a pH value in the range of from 3 to 5, especially in the range of from 3.8 to 4.5; and [0387] wherein the oxybutynin-comprising composition comprised in the piston syringe, including the piston syringe, is vapor sterilized, especially steam-sterilized.

    Aspect 40:

    [0388] 40. The piston syringe according to aspect 38 or 39, [0389] wherein the oxybutynin-comprising composition comprises the oxybutynin hydrochloride (oxybutynin-HCl) in a concentration of (1±0.4) mg/ml, especially in a concentration of (1±0.3) mg/ml, preferably in a concentration of (1±0.2) mg/ml, preferably in a concentration of (1±0.1) mg/ml, more preferably in a concentration of about 1 mg/ml.

    Aspect 41:

    [0390] 41. The piston syringe according to any of aspects 38 to 40, [0391] wherein the oxybutynin-comprising composition comprises the sodium chloride, calculated as sodium, in a concentration of (3.5±0.4) mg/ml, especially in a concentration of (3.5±0.3) mg/ml, preferably in a concentration of (3.5±0.2) mg/ml, preferably in a concentration of (3.5±0.1) mg/ml, more preferably in a concentration of about 3.5 mg/ml.

    Aspect 42:

    [0392] 42. The piston syringe according to any of aspects 38 to 41, [0393] wherein the piston syringe has a volume, especially a receiving volume for the oxybutynin-comprising composition, in the range of from 4 ml to 25 ml, especially in the [0394] range of from 6 ml to 20 ml, preferably in the range of from 8 ml to 15 ml, preferably in the range of from 9 ml to 12 ml, more preferably of about 10 ml; and/or [0395] wherein the piston syringe comprises the oxybutynin-comprising composition in an amount in the range of from 4 ml to 25 ml, especially in the range of from 6 ml to 20 ml, preferably in the range of from 8 ml to 15 ml, preferably in the range of from 9 ml to 12 ml, more preferably of about 10 ml.

    Aspect 43:

    [0396] 43. The piston syringe according to any of aspects 38 to 42, [0397] wherein the piston plug is formed from a chlorobutyl rubber or from a bromobutyl rubber, preferably from a bromobutyl rubber.

    Aspect 44:

    [0398] 44. The piston syringe according to any of aspects 38 to 43, [0399] wherein the piston syringe, especially the syringe cylinder, comprises a first opening, especially for receiving a syringe piston; and/or [0400] wherein the piston syringe comprises a syringe piston, especially wherein the syringe piston is formed from polypropylene or especially wherein the syringe piston is formed from a cycloolefin-(co)polymer (COP or COC).

    Aspect 45:

    [0401] 45. The piston syringe according to any of aspects 38 to 44, [0402] wherein the piston syringe comprises a second opening, especially a discharge opening, preferably for discharging and/or applying the oxybutynin-comprising composition.

    Aspect 46:

    [0403] 46. The piston syringe according to any of aspects 38 to 45, [0404] wherein the piston syringe comprises a closing element, especially a closing cap, preferably for closing the second opening, especially wherein the closing element is formed from a halobutyl rubber, especially from a chlorobutyl rubber or from a bromobutyl rubber, preferably from a bromobutyl rubber.

    Aspect 47:

    [0405] 47. The piston syringe according to any of aspects 38 to 46, [0406] wherein vapor sterilization is carried out under at least one of the conditions defined in Aspects 10 to 18; and/or [0407] wherein vapor sterilization is carried out under overkill conditions and/or at about 121° C. and/or for a duration of at least 15 min, especially of at least 20 min, preferably of about 20 min; and/or [0408] wherein vapor sterilization is carried out according to Pharmacopoea Europaea (Ph. Eur.), chapter 5.1.1 (07/2017:50101), especially under overkill conditions and/or at about 121° C. and/or for a duration of at least 15 min, especially of at least 20 min, preferably of about 20 min.

    Aspect 48:

    [0409] 48. The piston syringe according to any of aspects 38 to 47, [0410] wherein the sterile piston syringe filled with the sterile oxybutynin-comprising composition obtained after vapor sterilization and/or the oxybutynin-comprising composition obtained after vapor sterilization comprises a Sterility Assurance (SAL) value of at least 10.sup.−5, especially of at least 10.sup.−6, preferably of at least 10.sup.−7; and/or [0411] for instillation and/or for the preferred topical application of the oxybutynin-comprising composition into the urogenital region, especially into the bladder.

    Aspect 49:

    [0412] 49. A piston syringe, especially a disposable piston syringe, wherein the piston syringe comprises a syringe body, especially a syringe cylinder, on the one hand and a syringe piston with a piston plug on the other hand, wherein the syringe body is formed from a cycloolefin-(co)polymer (COP or COC) and wherein the piston plug is formed from a halobutyl rubber, especially from a chlorobutyl rubber or from a bromobutyl rubber, preferably from a bromobutyl rubber, especially piston syringe according to any of aspects 38 to 48, [0413] wherein the piston syringe is filled with a sterile oxybutynin-comprising composition, especially for use in the prophylactic and/or therapeutic treatment of neurogenic bladder dysfunction, especially neurogenic bladder voiding disorders, preferably neurogenic bladder dysfunction associated with detrusor hyperactivity and/or detrusor sphincter dyssynergy, [0414] wherein the oxybutynin-comprising composition comprises the oxybutynin in the form of the hydrochloride, the oxybutynin-comprising composition is configured as an aqueous composition and the oxybutynin-comprising composition comprises, in combination and each in effective, especially pharmaceutically effective, amounts, [0415] oxybutynin hydrochloride (oxybutynin-HCl) in a concentration of (1±0.4) mg/ml, especially in a concentration of (1±0.3) mg/ml, preferably in a concentration of (1±0.2) mg/ml, preferably in a concentration of (1±0.1) mg/ml, more preferably in a concentration of about 1 mg/ml, and [0416] sodium chloride, calculated as sodium, in a concentration of (3.5±0.4) mg/ml, especially in a concentration of (3.5±0.3) mg/ml, preferably in a concentration of (3.5±0.2) mg/ml, preferably in a concentration of (3.5±0.1) mg/ml, more preferably in a concentration of about 3.5 mg/ml, [0417] wherein the oxybutynin-comprising composition is adjusted to a pH value in the range of from 3 to 5, especially in the range of from 3.8 to 4.5, and/or wherein the oxybutynin-comprising composition has a pH value in the range of from 3 to 5, especially in the range of from 3.8 to 4.5; and [0418] wherein the oxybutynin-comprising composition comprised in the piston syringe, including the piston syringe, is vapor sterilized, especially steam-sterilized.

    Aspect 50:

    [0419] 50. A piston syringe, especially a disposable piston syringe, wherein the piston syringe comprises a syringe body, especially a syringe cylinder, on the one hand and a syringe piston with a piston plug on the other hand, wherein the syringe body is formed from a cycloolefin-(co)polymer (COP or COC) and wherein the piston plug is formed from a halobutyl rubber, especially from a chlorobutyl rubber or from a bromobutyl rubber, preferably from a bromobutyl rubber, especially piston syringe according to any of aspects 38 to 49, [0420] wherein the piston syringe is filled with a sterile oxybutynin-comprising composition, especially for use in the prophylactic and/or therapeutic treatment of neurogenic bladder dysfunction, especially neurogenic bladder voiding disorders, preferably neurogenic bladder dysfunction associated with detrusor hyperactivity and/or detrusor sphincter dyssynergy, [0421] wherein the oxybutynin-comprising composition comprises the oxybutynin in the form of the hydrochloride, the oxybutynin-comprising composition is configured as an aqueous composition and the oxybutynin-comprising composition comprises, in combination and each in effective, especially pharmaceutically effective, amounts, [0422] oxybutynin hydrochloride (oxybutynin-HCl) in a concentration of (1±0.4) mg/ml, especially in a concentration of (1±0.3) mg/ml, preferably in a concentration of (1±0.2) mg/ml, preferably in a concentration of (1±0.1) mg/ml, more preferably in a concentration of about 1 mg/ml, and [0423] sodium chloride, calculated as sodium, in a concentration of (3.5±0.4) mg/ml, especially in a concentration of (3.5±0.3) mg/ml, preferably in a concentration of (3.5±0.2) mg/ml, preferably in a concentration of (3.5±0.1) mg/ml, more preferably in a concentration of about 3.5 mg/ml, [0424] wherein the oxybutynin-comprising composition is adjusted to a pH value in the range of from 3 to 5, especially in the range of from 3.8 to 4.5, and/or wherein the oxybutynin-comprising composition has a pH value in the range of from 3 to 5, especially in the range of from 3.8 to 4.5; and [0425] wherein the oxybutynin-comprising composition comprised in the piston syringe, including the piston syringe, is vapor sterilized, especially steam-sterilized.

    Aspect 51:

    [0426] 51. A piston syringe, especially a disposable piston syringe, wherein the piston syringe comprises a syringe body, especially a syringe cylinder, on the one hand and a syringe piston with a piston plug on the other hand, wherein the syringe body is formed from a cycloolefin-(co)polymer (COP or COC) and wherein the piston plug is formed from a halobutyl rubber, especially from a chlorobutyl rubber or from a bromobutyl rubber, preferably from a bromobutyl rubber, especially piston syringe according to any of aspects 38 to 50, [0427] wherein the piston syringe is filled with a sterile oxybutynin-comprising composition, especially for use in the prophylactic and/or therapeutic treatment of neurogenic bladder dysfunction, especially neurogenic bladder voiding disorders, preferably neurogenic bladder dysfunction associated with detrusor hyperactivity and/or detrusor sphincter dyssynergy, [0428] wherein the oxybutynin-comprising composition comprises the oxybutynin in the form of the hydrochloride, the oxybutynin-comprising composition is configured as an aqueous composition and the oxybutynin-comprising composition comprises, in combination and each in effective, especially pharmaceutically effective, amounts, [0429] oxybutynin hydrochloride (oxybutynin-HCl) in a concentration of about 1 mg/ml and [0430] sodium chloride, calculated as sodium, in a concentration of about 3.5 mg/ml, [0431] wherein the oxybutynin-comprising composition is adjusted to a pH value in the range of from 3.8 to 4.5 and/or wherein the oxybutynin-comprising composition has a pH value in the range of from 3.8 to 4.5; and [0432] wherein the oxybutynin-comprising composition comprised in the piston syringe, including the piston syringe, is vapor sterilized, especially steam-sterilized.

    Aspect 52:

    [0433] 52. A piston syringe, especially a disposable piston syringe, wherein the piston syringe comprises a syringe body, especially a syringe cylinder, on the one hand and a syringe piston with a piston plug on the other hand, wherein the syringe body is formed from a cycloolefin-(co)polymer (COP or COC) and wherein the piston plug is formed from a halobutyl rubber, especially from a chlorobutyl rubber or from a bromobutyl rubber, preferably from a bromobutyl rubber, especially piston syringe according to any of aspects 38 to 51, [0434] wherein the piston syringe is filled with a sterile oxybutynin-comprising composition, especially for use in the prophylactic and/or therapeutic treatment of neurogenic bladder dysfunction, especially neurogenic bladder voiding disorders, preferably neurogenic bladder dysfunction associated with detrusor hyperactivity and/or detrusor sphincter dyssynergy, [0435] wherein the oxybutynin-comprising composition comprises the oxybutynin in the form of the hydrochloride, the oxybutynin-comprising composition is configured as an aqueous composition and the oxybutynin-comprising composition comprises, in combination and each in effective, especially pharmaceutically effective, amounts, [0436] oxybutynin hydrochloride (oxybutynin-HCl) in a concentration of about 1 mg/ml and [0437] sodium chloride, calculated as sodium, in a concentration of about 3.5 mg/ml, [0438] wherein the oxybutynin-comprising composition is adjusted to a pH value in the range of from 3.8 to 4.5 and/or wherein the oxybutynin-comprising composition has a pH value in the range of from 3.8 to 4.5; and [0439] wherein the oxybutynin-comprising composition comprised in the piston syringe, including the piston syringe, is vapor sterilized, especially steam-sterilized, [0440] wherein the vapor sterilization is carried out under overkill conditions and/or at about 121° C. and/or for a duration of at least 15 min, especially of at least 20 min, preferably of about 20 min, and/or [0441] wherein the vapor sterilization is carried out according to Pharmacopoea Europaea (Ph. Eur.), chapter 5.1.1 (07/2017:50101), especially under overkill conditions and/or at about 121° C. and/or for a duration of at least 15 min, especially of at least 20 min, preferably of about 20 min.

    Aspect 53:

    [0442] 53. A piston syringe, especially a disposable piston syringe, wherein the piston syringe comprises a syringe body, especially a syringe cylinder, on the one hand and a syringe piston with a piston plug on the other hand, wherein the syringe body is formed from a cycloolefin-(co)polymer (COP or COC) and wherein the piston plug is formed from a halobutyl rubber, especially from a chlorobutyl rubber or from a bromobutyl rubber, preferably from a bromobutyl rubber, especially piston syringe according to any of aspects 38 to 52, [0443] wherein the piston syringe is filled with a sterile oxybutynin-comprising composition, especially for use in the prophylactic and/or therapeutic treatment of neurogenic bladder dysfunction, especially neurogenic bladder voiding disorders, preferably neurogenic bladder dysfunction associated with detrusor hyperactivity and/or detrusor sphincter dyssynergy, [0444] wherein the oxybutynin-comprising composition comprises the oxybutynin in the form of the hydrochloride, the oxybutynin-comprising composition is configured as an aqueous composition and the oxybutynin-comprising composition comprises, in combination and each in effective, especially pharmaceutically effective, amounts, [0445] oxybutynin hydrochloride (oxybutynin-HCl) in a concentration of about 1 mg/ml and [0446] sodium chloride, calculated as sodium, in a concentration of about 3.5 mg/ml, [0447] wherein the oxybutynin-comprising composition is adjusted to a pH value in the range of from 3.8 to 4.5 and/or wherein the oxybutynin-comprising composition has a pH in the range of from 3.8 to 4.5; and [0448] wherein the piston syringe comprises a volume, especially a receiving volume for the oxybutynin-comprising composition, of about 10 ml, and/or wherein the piston syringe comprises the oxybutynin-comprising composition in an amount of about 10 ml, [0449] wherein the oxybutynin-comprising composition comprised in the piston syringe, including the piston syringe, is vapor sterilized, especially steam-sterilized.

    Aspect 54:

    [0450] 54. A packaging unit comprising at least one packaging and at least one piston syringe, especially disposable piston syringe, as defined in one of Aspects 38 to 53, wherein the piston syringe is inserted into the packaging and/or is present in the packaging.

    Aspect 55:

    [0451] 55. A kit, especially an application and/or instillation system, comprising (i) at least one oxybutynin-comprising composition, as defined in one of Aspects 26 to 37, present in a piston syringe, especially disposable piston syringe, especially as defined in one of Aspects 38 to 53; (ii) (a) at least one application and/or instillation device connectable to the piston syringe, especially in the form of an instillation tube or the like, preferably in the form of a (urinary bladder) catheter, and/or (b) at least one connection device, especially an adapter, connectable to the piston syringe for connecting to an application and/or instillation device, especially in the form of an instillation tube or the like, preferably in the form of a (urinary bladder) catheter; and optionally (iii) at least one application and/or instillation manual.

    Aspect 56:

    [0452] 56. A kit, especially an application and/or instillation system, comprising (i) at least one piston syringe, especially a disposable piston syringe, as defined in one of Aspects 38 to 53, and/or at least one packaging unit as defined in Aspect 54; (ii) (a) at least one application and/or instillation device connectable to the piston syringe, especially in the form of an instillation tube or the like, preferably in the form of a (urinary bladder) catheter, and/or (b) at least one connecting device, especially an adapter, connectable to the piston syringe for connecting to an application and/or instillation device, especially in the form of an instillation tube or the like, preferably in the form of a (urinary bladder) catheter; and optionally (iii) at least one application and/or instillation manual.

    Aspect 57:

    [0453] 57. Use of a piston syringe, especially a disposable piston syringe, in a method for producing a sterile oxybutynin-comprising composition, especially as defined in one of Aspects 1 to 25, [0454] wherein the piston syringe comprises a syringe body, especially a syringe cylinder, on the one hand and a syringe piston with a piston plug on the other hand, wherein the syringe body is formed from a cycloolefin-(co)polymer (COP or COC) and wherein the piston plug is formed from a halobutyl rubber, [0455] wherein the piston syringe is filled with the sterile oxybutynin-comprising composition, especially for use in the prophylactic and/or therapeutic treatment of neurogenic bladder dysfunction, especially neurogenic bladder voiding disorders, preferably neurogenic bladder dysfunction associated with detrusor hyperactivity and/or detrusor sphincter dyssynergia, [0456] wherein the oxybutynin-comprising composition comprises the oxybutynin in the form of the hydrochloride, the oxybutynin-comprising composition is configured as an aqueous composition and the oxybutynin-comprising composition comprises, in combination and each in effective, especially pharmaceutically effective, amounts, [0457] oxybutynin hydrochloride (oxybutynin-HCl) in a concentration of (1±0.5) mg/ml and [0458] sodium chloride, calculated as sodium, in a concentration of (3.5±0.5) mg/ml, [0459] wherein the oxybutynin-comprising composition is adjusted to a pH value in the range of from 3 to 5, especially in the range of from 3.8 to 4.5, and/or wherein the oxybutynin-comprising composition has a pH value in the range of from 3 to 5, especially in the range of from 3.8 to 4.5; and [0460] wherein the oxybutynin-comprising composition comprised in the piston syringe, including the piston syringe, is vapor sterilized, especially steam-sterilized.

    Aspect 58:

    [0461] 58. Use of vapor sterilization, especially steam sterilization, in a method for producing a sterile oxybutynin-comprising composition in a preferably ready-to-use piston syringe, especially disposable piston syringe, and/or for producing a preferably ready-to-use, sterile piston syringe filled with an oxybutynin-comprising composition, especially disposable piston syringe, especially as defined in one of aspects 1 to 25, [0462] wherein the piston syringe comprises a syringe body, especially a syringe cylinder, on the one hand and a syringe piston with a piston plug on the other hand, wherein the syringe body is formed from a cycloolefin-(co)polymer (COP or COC) and wherein the piston plug is formed from a halobutyl rubber; [0463] wherein in the oxybutynin-comprising composition the oxybutynin is used in the form of the hydrochloride, the oxybutynin-comprising composition is configured as an aqueous composition and the oxybutynin-comprising composition comprises, in combination and in each case in effective, especially pharmaceutically effective, amounts, [0464] oxybutynin hydrochloride (oxybutynin-HCl) in a concentration of (1±0.5) mg/ml and [0465] sodium chloride, calculated as sodium, in a concentration of (3.5±0.5) mg/ml, [0466] wherein the oxybutynin-comprising composition is adjusted to a pH value in the range of from 3 to 5, especially in the range of from 3.8 to 4.5, and/or wherein the oxybutynin-comprising composition has a pH value in the range of from 3 to 5, especially in the range of from 3.8 to 4.5; and [0467] wherein the piston syringe filled with the oxybutynin-comprising composition and/or the oxybutynin-comprising composition provided in the piston syringe is vapor sterilized, especially steam-sterilized.

    Aspect 59:

    [0468] 59. Piston syringe according to any of Aspects 38 to 53, packaging unit according to Aspect 54, kit according to Aspect 55 or 56, use according to Aspect 57 and/or use
    according to Aspect 58, each characterized by one or more of the features of Aspect 1 to 37.

    [0469] All aspects of the present invention, as delineated hereinabove, form part of the present invention also in their respective combinations.