A new membrane or matrix for regulation of permeability of drugs
(57) Abstract:Describes a method of regulating the permeability of the drug over an extended period of time using elastomer-based siloxane comprising dispersing the above drugs in the above elastomer-based siloxane with the formation of the matrix, or the conclusion of the above drugs as the core of the membrane containing the above-mentioned elastomer-based siloxane, and the above-mentioned elastomer contains 3,3,3-triptoreline group attached to the Si-atoms of parts of the siloxane, with from 1 to about 50% of the substituents attached to the Si atoms in the siloxane units are 3,3,3-triptoreline groups, and elastomer made of or from (i) a mixture consisting of (a) unsubstituted fluorine-based polymer of siloxane and (b) fluorinated polymer-based siloxane, and the above polymer contains 3,3,3-triptoreline group attached to the Si-atoms of parts of the siloxane, or ii) a single polymer-based siloxane containing 3,3,3-triptoreline group attached to the Si-atoms of parts of the siloxane, where the above-mentioned polymer or smester, through which the drug permeates with the desired speed and which is attached to the membrane mechanical properties. 4 C.p. f-crystals, 6 PL. The scope of the inventionThis invention relates to a new membrane or matrix for regulation of permeability of drugs, and the above membrane or matrix is based on the siloxane polymer. The invention relates to a method for producing the above-mentioned elastomer.The BACKGROUND TO the INVENTIONUsed in this publication and other materials describing the background to the invention, in particular cases, describing additional details of practical application, included in this text by reference.Polysiloxane, such as poly(dimethylsiloxane) (PDMS), are highly suitable for use as a membrane or matrix, regulating the permeability of drugs in different dosage forms, in particular, implants and intrauterine (IU) systems. Polysiloxane are physiologically inert, and it turned out that a wide group of medicines shows the ability to penetrate through polysilk the sources is known, that adding groups of poly(aquisition), i.e. REO-groups, PDMS is a polymer can increase the permeability of drugs. Publication KL Ullman et al., Journal of Controlled Release 10 (1989), 251-260, describes a membrane made of blockcopolymer, which contains REO and PDMS, and the penetration of various steroids through these membranes. In addition, it is known that membrane based on modified PDMS-polymers, in which a certain number of methyl substituents at the Si-atoms substituted triptoreline groups, reduce the penetration of drugs. Publication Ying Sun et al., Journal of Controlled Release, 5 (1987), 69-78, describes the impact of the membranes, made of PDMS, replaced by cryptocaryon PDMS and PDMS/REO/emission spectra obtained for pure (where represents the emission spectra obtained for pure poly(methyl methacrylate)) on the permeability of androgen and gestagennah steroids. The study shows that the permeability for both groups of steroids was lower for membranes made from substituted cryptocaryon PDMS than for membranes made of unmodified PDMS. However, the publication does not disclose any elastomer derived from substituted cryptocaryon PDMS.The PURPOSE of the INVENTIONThe aim of the invention is to develop a method of regulation carstone agent reaches the desired speed and which is attached to the membrane mechanical properties.The aim of the invention is, in particular, a method of regulating drugs with hormonal activity, using elastomer, the penetration of drugs through which you can control.A particularly important aim of this invention is to provide elastomer, which retards the penetration of drugs compared with elastomers from normal PDMS.BRIEF description of the INVENTIONThe invention relates to a method of regulating the permeability of the drug over an extended period of time using a membrane or matrix consisting of elastomer-based siloxane comprising dispersing the drug in a specific elastomer-based siloxane with the formation of the membrane or matrix, or the conclusion of the above drugs as the core of the membrane containing the above-mentioned elastomer-based siloxane, and the specified elastomer contains 3,3,3-triptoreline group attached to the Si-atoms of parts of the siloxane, with from 1 to about 50% of the substituents attached to the Si atoms in the siloxane units, are 3,3,3-triptorelin the basis of siloxane and (b) fluorinated polymer-based siloxane, moreover, the above polymer contains 3,3,3-triptoreline group attached to the Si-atoms of parts of the siloxane, orii) a single polymer-based siloxane containing 3,3,3-triptoreline group attached to the Si-atoms of parts of the siloxane, with the above-mentioned polymer or mixture of polymers cross linked with the formation of the elastomer.DETAILED description of the INVENTIONGeneral description elastomerThe term “elastomer-based siloxane” should be understood as covering the elastomers obtained from poly(disubstituted siloxanes), in which the substituents are primarily lower alkyl, preferably alkyl groups of 1-6 carbon atoms, or phenyl group, where the above-mentioned alkyl or phenyl can be substituted or unsubstituted. Widely used and preferred polymer of this type is poly(dimethylsiloxane) or PDMS.According to the invention a certain number of substituents attached to the Si-atoms of parts of the siloxane in the elastomer must be 3,3,3-triptoreline groups. This elastomer can be obtained in various ways. According to one variant of the elastomer alkylsilanes), in which a certain number of alkyl groups in the Si atoms substituted 3,3,3-triptoreline groups. A preferred example of such polymers is poly(3,3,3-triphosphorylation), whose structure is shown below as compound (IA polymer of this type, in which approximately 50% of methyl substituents at the Si-atoms are replaced by 3,3,3-triptoreline group, is commercially available. The term “approximately 50%” means that the degree of substitution 3,3,3-triptoreline groups is actually slightly below 50%, because the polymer must contain a certain number (about 0.15% of deputies) Poperechnaya groups such as vinyl groups or terminal vinyl groups. Such polymers having a low degree of substitution 3,3,3-triptoreline groups, can be easily synthesized.Action 3,3,3-triptoreline groups on the slow permeability of drugs through the membrane elastomer depends on the number of these groups. In addition, this action depends on the drug. If the elastomer obtained only from a single polymer, it is necessary to obtain and use polymers with yet another variant, which is especially preferred in cases where you want to create suitable elastomers for several different medicines, you must associate transverse bracing mixture containing (a) unsubstituted fluorine-based polymer of siloxane and (b) fluorinated polymer-based siloxane in which the above polymer contains 3,3,3-triptoreline groups associated with the Si atoms of parts of the siloxane. The first ingredient of the mixture, unsubstituted fluorine polymer can be any poly(disubstituted siloxane), where the substituents are primarily lower alkyl, preferably alkyl groups containing 1-6 carbon atoms, or phenyl group, where the above-mentioned alkyl or phenyl can be substituted or unsubstituted. Preferred unsubstituted fluorine polymer is PDMS. The second ingredient of the mixture, fluoro-substituted polymer can be, for example, poly(dialkylzincs), in which a certain number of alkyl groups in Si-atoms are replaced by 3,3,3-triptoreline group. Preferred examples of such polymers, as mentioned above, is a poly(3,3,3-triphosphorylation. Particularly preferred polymer of this type is the polymer Meucci available polymer, in which approximately 50% of methyl substituents at the Si-atoms substituted 3,3,3-triptoreline groups. Elastomer with a large delay permeability effect can be obtained solely or mainly for the use of the above-mentioned polymer. Elastomers with less retarding effect of the permeability of drugs can be obtained by using mixtures with increasing amounts of unsubstituted fluorine-based polymer of siloxane.Preferably the elastomer must contain a filler, such as amorphous silica, to give a membrane made of the above elastomer, a sufficient strength.Description of the method of producing elastomerAccording to one variant of the elastomer get through the cross-linking vinyl-functional polysiloxane component and kremnievykh-functional Poperechnaya agent in the presence of a catalyst.Cross-linking means reaction joining kremnievykh-functional Poperechnaya agent with carbon-carbon double bond wikifunctions polysiloxane component.
General formula (1)mol
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to a therapeutic preparation as granule designated for oral administration and adopted for providing immediate and prolonged release of a medicinal agent. Each granule comprises an internal core prepared by extrusion-spheronization method that comprises at least one medicinal agent with the modified release of one or more water-soluble and/or lipid-soluble vitamins, and external layer including at least one medicinal agent with sustained-release of one or more water-soluble vitamins. Composition involves also a coating between internal core and external layer for sustained-release of components wherein indicated coating regulates releasing a medicinal agent from internal core, and a dosed formulation for oral administration also, a method for preparing and granule preparing by this method. Invention provides preparing a vitamin-containing preparation with sustained-release of therapeutic agent.
EFFECT: valuable pharmaceutical properties of composition.
15 cl, 2 ex
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to a method for treatment of nicotine dependence in a person using a medicinal formulation with controlled release (MFCR) comprising 5,8,14-triazatetracyclo[10.3.02,11.04,9]hexadeca-2(11),3,5,7,9-pentaene or its pharmaceutically acceptable salt taken in the effective dose, and to a method for reducing adverse effect of this active component. Method involves using MFCR that comprises agents of this active component for its administration to a patient at the rate less about 6 mg/h resulting to administration of at least about 0.1 mg of compound or its salt for 24 h. The initial administration of MFCR results to plasma maximal concentration (Cmax) of active component in average from 10% to 80% of the corresponding Cmax determined for the equal dose of active component in form of bolus with immediate release, and to increasing time of value Cmax in plasma (Tmax) in initial administration in average by 50% relatively to the corresponding Tmax value determined for the equal dose of active component in form of bolus of immediate release. Also, MFCR releases active component in vireo at the rate less 6 mg/h in the dissolving testing using device USP-2 (USA Pharmacopoeia) in order to provide the dissolving time of 50 wt.-% of active component from 1 to 15 h. Indicated agents comprise a tablet with matrix, multi-particles, covered multi-particles or tablet with a cover. Invention provides carrying out the effective treatment of nicotine dependence and without symptoms of adverse effects of active component, in particle, without nausea.
EFFECT: improved method of treatment.
7 cl, 19 tbl, 13 ex