RELEASE OF ACTIVE INGREDIENTS USING SILICON-CONTAINING POLYMERS

Abstract

Active substances for which controlled release is desired, are released by a process in which a shaped body (S) containing a composition (C) comprises a silicone-containing polymer (P) containing at least one Si—C bonded amino acid group and active substance (A) is contacted with water, resulting in the release of active substance (A) from the composition (C).

Claims

1.-13. (canceled)

14. A shaped body comprising at least one composition comprising a silicone-containing polymer (P) and an active substance (A), wherein the silicone-containing polymer (P) contains at least one siloxane unit of the formula I and optionally one or more units of the formula II
R.sup.1.sub.b(X).sub.cSiO.sub.[4−(b+c)]/2  (I),
R.sup.2.sub.aSiO.sub.(4−a)/2  (II), in which R.sup.1 and R.sup.2 independently represent hydrogen or an unbranched, branched or cyclic, saturated or unsaturated alkyl group having 1 to 20 carbon atoms, an aryl group, or an aralkyl group, wherein individual nonadjacent methylene units are optionally replaced by —O—, —CO—, —COO—, —OCO— or —OCOO—, —S— or NR.sup.x groups or by an oxyalkylene group of the formula (—O—CH.sub.2—CHR.sup.3—).sub.d, R.sup.3 represents hydrogen or alkyl, R.sup.x represents hydrogen or a C.sub.1-C.sub.10 hydrocarbon radical that is unsubstituted or substituted with —CN or halogen, X represents a radical bearing at least one amino acid unit and attached to a silicon atom of the silicon-containing polymer via a carbon atom, and having the formula
—Y—NR.sup.4—(CH.sub.2).sub.e—CR.sup.5R.sup.6—COOM, wherein M represents hydrogen, metal or an ammonium moiety NR.sup.10.sub.4.sub.+, R.sup.10 independently represents hydrogen or C.sub.1-C.sub.12, alkyl, aryl or aralkyl, R.sup.4 represents hydrogen or a straight-chain, branched or cyclic, saturated or unsaturated alkyl group having 1 to 20 carbon atoms or aryl group or aralkyl group, wherein individual nonadjacent methylene units are optionally replaced by —O—, —CO—, —COO—, —OCO— or —OCOO—, —S— or NR.sup.x groups or by an oxyalkylene group of the general formula (—O—CH.sub.2—CHR.sup.3—).sub.d, R.sup.5 and R.sup.6 independently represent hydrogen or straight-chain, branched or cyclic, saturated or unsaturated alkyl groups having 1 to 20 carbon atoms or aryl groups or aralkyl groups, wherein individual nonadjacent methylene units are optionally replaced by —O—, —CO—, —COO—, —OCO— or —OCOO—, —S— or NR.sup.x groups, wherein R.sup.5 or R.sup.6 are optionally attached to R.sup.4, Y represents a straight-chain, branched, cyclic, saturated or mono- or polyunsaturated C.sub.1 to C.sub.100 alkylene radical attached to the organosilicon compound via a carbon atom, in which individual carbon atoms are optionally replaced by oxygen, nitrogen or sulphur atoms, a is 0, 1, 2 or 3, b is 0, 1, or 2, c is 1, 2 or 3 d is an integer from 1 to 100. b+c is 1, 2, 3 or 4, and f is an integer from 0 to 50.

15. The shaped body of claim 14, in which R.sup.1 and R.sup.2 independently represent an unbranched, branched, or cyclic, saturated or unsaturated alkyl group having 1 to 6 carbon atoms.

16. The shaped body of claim 14, in which M is independently from hydrogen, sodium, potassium, or ammonium moiety.

17. The shaped body of claim 15, in which M is independently from hydrogen, sodium, potassium, or ammonium moiety.

18. The shaped body of claim 14, in which e represents values from 0 to 5.

19. The shaped body of claim 15, in which e represents values from 0 to 5.

20. The shaped body of claim 16, in which cerepresents values from 0 to 5.

21. The shaped body of claim 14, in which the shaped body contains further polymers other than silicone-containing polymer (P).

22. The shaped body of claim 14, in which the silicone-containing polymer (P) contains blocks of siloxane units of the formula and optionally one or more units of the formula II, and organic blocks which interrupt blocks of siloxane units.

23. The shaped body of claim 14, in which the active substance (A) exerts an effect on a biological system.

24. The shaped body of claim 14, in which the release of the active substance (A) occurs over a period of not less than 1 minute to not more than 5 years.

25. The shaped body of claim 13, wherein the shaped body has the form of granules, sticks, flakes, films or materials containing cavities.

26. The shaped body of claim 25, wherein the films or materials containing cavities are membranes, foams, or honeycomb structures.

27. A process for the production of a shaped body of claim 14, in which a solution of the silicone-containing polymer (P) is admixed with the active substance (A) in the desired amount and the resulting mixture is concentrated by evaporation to form the composition.

28. The process of claim 27, wherein the composition is a solid composition which has been comminuted after concentration by evaporation.

29. A process for the release of an active substance (A) from a shaped body of claim 14, wherein the composition is brought into contact with a damp material, damp surfaces, aqueous liquids, or directly with water in a gas phase.

30. The shaped body of claim 14, which supplies a medicament.

Description

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0056] The silicone-containing polymer (P) may contain blocks of siloxane units of the general formula I and no or at least one unit of the general formula II and organic blocks, through which the blocks of siloxane, units are interrupted. The organic blocks may be attached to the blocks siloxane units, for example through urea moieties, urethane moieties or ester groups. The proportion of organic blocks is preferably not less than 2 and not more than 300 parts by weight, more preferably not more than 30 parts by weight, most preferably not more than 10 parts by weight per 100 parts by weight of siloxane units of the general formula I and II.

[0057] The polymers (P) used for the controlled release of active substances (A) may be crosslinked or uncrosslinked.

[0058] The composition (C) may contain further substances that are present either as solids or in dissolved form.

[0059] Examples of solids that may be used are fillers, for example colloidal silica, silicates, zeolites or carbon-based fillers such as carbon black.

[0060] The composition (C) may also contain liquids or liquid mixtures as additives. These components may accelerate, or reduce the release of the active substance (A).

[0061] The proportion of liquid additives is preferably not less than 0.01 and not more than 1000 parts by weight, more preferably not less than 0.1 and not more than 100 parts by weight, and in particular not less than 1 and not more than 10 parts by weight per 100 parts by weight of siloxane units of the general formula I and II.

[0062] Preferred liquid additives are water, organic liquids or mixtures thereof, for example. further siloxanes, esters, monohydric or polyhydric alcohols, ethers, and/or hydrocarbons.

[0063] The release of one or more active substances (A) is achieved for example through contact of the composition (C) with damp materials and surfaces or aqueous liquids or indirectly through exposure to water via the gas phase.

[0064] Within the shaped body (S) there may be further layers between the composition (C) and the water-containing medium that permit the transport of water in either liquid or gaseous form. The transport of water through these layers in liquid or gaseous form may take place through pores or through channels.

[0065] Examples of shaped bodies (S) are granules, sticks, flakes, films, materials containing cavities, for example, membranes, foams or honeycomb structures.

[0066] Active substances (A) in this context are preferably substances that exert an effect on biological systems.

[0067] These include, drug substances (active pharmaceutical ingredients), hormones, vitamins, trace elements, crop protection agents, pheromones, phytohormones, fragrances, enzymes, coenzymes or antibodies, chelating agent, metals or metal ions, light absorbers, antioxidants, and pigments.

[0068] These active substance groups are defined and classified for example Römpp, Chemie Lexikon Online, Thieme, Stuttgart 2015.

[0069] The shaped body (S) may be produced, for example, by admixing a solution of the polymer (P) with the active substance (A) in the desired amount and then preferably concentrating the resulting mixture by evaporation. This forms composition (C). This ensures, for example, a uniform distribution of the active. substance (A) in the polymeric matrix of the silicone-containing polymer (P).

[0070] Another possibility is to bring the shaped body (S) containing the polymer (P) into contact with liquid, for example water, or with a water containing mixture, that contains the active substance (A). The active substance (A) can in this manner diffuse from the liquid into the polymer (P). This likewise forms composition (C).

[0071] After concentration by evaporation or after contact with liquid, the solid composition (C) may if necessary be comminuted to produce smaller shaped bodies (S). The solution of the polymer (P) containing the active substance (S) may also be transferred to molds and concentrated by evaporation.

[0072] The release, of active substance (A) occurs preferably over periods of not less than 1 minute to not more than 5 years, more preferably over periods of not less than 1 h to not more than 1 year, most preferably over periods of not less than 1 day to 6 months.

[0073] The release of active substance (A) occurs preferably at temperatures of not less than −20° C. aid not more. than +200° C., more preferably of not less than 0° C. and not more. than 100° C., most preferably of not less than +10° C. and not more than +50° C.

[0074] The release of active substance (A) occurs preferably at a pressure between not less than 0.1 mbar to not more than 50 bar, more preferably not less than 100 mbar to not more than 20 bar, especially preferably at not less than 0.9 bar to 10 bar.

[0075] The release of active substance (A) may also be controlled through the pH or change in the pH or also electrically through change in the potential.

[0076] In the examples that follow, unless otherwise stated in each case, all amounts and percentages shown are based on weight and all temperatures are 20° C.

[0077] The meanings of all abovementioned symbols in the abovementioned formulae are in each case independent of one another. The silicon atom is tetravalent in all formulae.

EXAMPLE 1 (PREPARATION OF THE POLYMERIC SILICONE-CONTAINING MATERIAL (P))

[0078] 50 g of a silicone polymer terminally functionalized with glycidoxypropyl groups and having a molecular weight of approximately 900 is dissolved in 75 ml of methanol and added to a solution of 10 g of lysine in 260 g of methanol. The clear polymer solution is boiled under reflux for 9 hours, filtered, and concentrated to a solid content of approximately 40%.

EXAMPLE 2 (INTRODUCTION OF THE ACTIVE SUBSTANCE (A) INTO THE POLYMER MATRIX)

[0079] 352 mg of nicotinic acid is dissolved in 6.0 g of the polymer solution prepared according to example 1. The active substance-containing polymer solution is poured into a Teflon mold. The solvent is evaporated to yield a clear polymer film containing nicotinic acid.

EXAMPLE 3

[0080] 489 mg of the polymer film containing 22.9 mg of nicotinic acid obtained according to example 2 is dissolved in. 3 ml of water at 20° C. After specified times t, the amount of nicotinic acid dissolved in water is determined by NMR spectroscopy.

[0081] The values shown below in Table 1 are obtained:

TABLE-US-00001 TABLE 1 mg nicotinic t (hours) acid in H.sub.2O 0 0 1 0.0369 4 0.0885 24 0.233 96 0.462