HEPOKUR CEYLAN (TR)
HEPOKUR ALI IHSAN (TR)
ANISHKUMAR GUPTA ET AL: "Interpenetrating polymeric network hydrogel for stomach-specific drug delivery of clarithromycin: Preparation and evaluation", ASIAN JOURNAL OF PHARMACEUTICS, vol. 4, no. 4, 1 January 2010 (2010-01-01), IN, pages 179, XP055359956, ISSN: 0973-8398, DOI: 10.4103/0973-8398.76738
A. L. VICOSA ET AL: "Effect of sepiolite on the physical properties and swelling behavior of rifampicin-loaded nanocomposite hydrogels", EXPRESS POLYMER LETTERS, vol. 3, no. 8, 1 January 2009 (2009-01-01), pages 518 - 524, XP055360045, ISSN: 1788-618X, DOI: 10.3144/expresspolymlett.2009.64
NURSEVIN ÖZTOP H ET AL: "Poly(acrylamide/maleic acid)-sepiolite composite hydrogels for immobilization of invertase", POLYMER BULLETIN, SPRINGER, BERLIN, DE, vol. 64, no. 1, 18 July 2009 (2009-07-18), pages 27 - 40, XP019779321, ISSN: 1436-2449
CEYLAN HEPOKUR ET AL: "The Interaction of Clarithromycin with a New Polymer-Based Nipam-Sepiolite", LATIN AMERICAN JOURNAL OF PHARMACY AM. J. PHARM, vol. 36, no. 2, 1 January 2017 (2017-01-01), pages 301 - 307, XP055359940, ISSN: 2362-3853
| CLAIMS 1. A production method (100) developed for obtaining polymeric hydrogel to be used in drug release; comprising the steps of - preparing the monomer mixture (101), dissolving the mixture in distilled water (102), adding initiator and accelerator to the solution (103), shaping the hydrogels formed upon allowing the polymeric material produced as a result of the reaction to rest (104), - washing and drying the polymeric hydrogels (105); - and characterized in that 8.1-10.1 mmol nipam, 1-3 mmol acrylamide, 0.9- 1.1 mmol maleic acid and 0.5-0.7 mmol Ν,Ν'-methylenebisacrylamide are used in the step of preparing the monomer mixture (101). 2. Method (100) for polymeric hydrogel production for use in drug release according to Claim 1, characterized by the step of preparing the monomer mixture (101) wherein 50-70 mg sepiolite is also added to the mixture and thus a composite structure is formed. 3. Method (100) for polymeric hydrogel production for use in drug release according to Claim 1 or 2, characterized by the step of dissolving the mixture in 4.5 ml distilled water (102)adding initiator and accelerator to the solution as in. 4. Method (100) for polymeric hydrogel production for use in drug release according to Claim 3, characterized by the step of adding 0.1 mmol ammonium persulfate (APS) as initiator and 1.67 mmol Ν,Ν,Ν',Ν'- tetramethylethylenediamine (TEMED) as accelerator to the solution (103). 5. Method (100) for polymeric hydrogel production for use in drug release according to Claim 4, characterized by the step of filling the polymeric material produced as a result of the reaction into pipettes and shaping the hydrogels, which are formed upon resting the polymeric material at a temperature of 22-25 °C for 24-30 hours, by cutting them in 3-4 mm sizes (104). 6. Method (100) for polymeric hydrogel production for use in drug release according to Claim 4, characterized by the step of washing the shaped polymeric hydrogels finally with double-distilled water and drying them in a drying oven (105). 7. Composite polymeric hydrogels produced with a method according to Claim 2, which combine the ability of clay adsorbing different components and the elasticity and permeability features of the hydrogel structure in one body. 8. Composite polymeric hydrogels according to Claim 7, which are suitable for controlled release of clarithromycin active ingredient. |
IN DRUG RELEASE
DESCRIPTION
Field of the Invention
The present invention relates to composite polymeric hydrogels used for controlled drug release in biomedical field by means of their improved water- swelling property and the production method thereof.
Background of the Invention
In drug release, the polymeric structure, to which the active ingredient is adsorbed and which undertakes the task of carrying the active ingredient, is as important as the active ingredient, because this polymeric structure should convey the active ingredient to the target area in optimum conditions without any damage. In addition, the synthesized polymeric structure should not interact with the active ingredient, should be biocompatible and biodegradable, and should be produced easily and inexpensively. For this reason, a specific polymeric structure carrier is synthesized for each active ingredient and the drug-polymer interactions are analyzed.
Network structured water- swelling substances are called hydrogels. Since polymeric hydrogels have features such as response to pH, temperature and ion concentration, and swelling rapidly and controlling diffusion of the drug molecules by means of its macropores; they are commonly used in biomedical applications and particularly in controlled drug release. Today, many diseases threatening human health can be treated by means of controlled drug release technique. Accordingly, different active ingredients and different polymeric structures which will enable release of these ingredients are developed for treatment of different diseases. Swelling abilities and mechanical stabilities of hydrogels are also still in development process. Summary of the Invention
The objective of the present invention is to provide a polymeric hydrogel production method which makes possible release of many drugs in different periods of time.
Another objective of the present invention is to provide a polymeric hydrogel production method in which monomers such as N-isopropylacrylamide (nipam), acrylamide, maleic acid and Ν,Ν'-methylenebisacrylamide are used. A further objective of the present invention is to provide a composite polymeric hydrogel production method whose swelling property, thermal and mechanical stability are improved by means of clay addition.
Detailed Description of the Invention
The flowchart related to a method for production of polymeric hydrogel to be used in drug release in order to fulfill the objective of the present invention is given in Figure 1. The production method (100) of the present invention comprises the steps of
- preparing the monomer mixture (101),
- dissolving the mixture in distilled water (102),
- adding initiator and accelerator to the solution (103),
- shaping the hydrogels formed upon allowing the polymeric material produced as a result of the reaction to rest (104),
- washing and drying the polymeric hydrogels (105). In the polymeric hydrogel production method (100) of the present invention, firstly the mixture comprising a plurality of monomers is prepared (101). Accordingly, N-isopropylacrylamide (nipam), acrylamide, maleic acid and Ν,Ν'- methylenebisacrylamide monomers are used. In a preferred embodiment of the invention, the range of amounts used are as follows: 8.1-10.1 mmol nipam, 1-3 mmol acrylamide, 0.9-1.1 mmol maleic acid and 0.5-0.7 mmol Ν,Ν'- methylenebisacrylamide. In another embodiment of the invention, when the monomer mixture is being prepared (101), clay material is added therein thereby providing a composite structure. This mixture is preferably comprised of 8.1-10.1 mmol nipam, 1-3 mmol acrylamide, 0.9-1.1 mmol maleic acid, 0.5-0.7 mmol Ν,Ν'- methylenebisacrylamide and 50-70 mg sepiolite.
The prepared monomer mixture is then dissolved in 4.5 ml distilled water (102). In order to initiate and accelerate the reaction, the initiator and accelerator are added into the monomer solution respectively (103). As initiator, 0.1 mmol ammonium persulfate (APS), and as accelerator, 1.67 mmol Ν,Ν,Ν',Ν'- tetramethylethylenediamine (TEMED) are used.
The polymeric material resulting at the end of the reaction is taken to a container to be allowed to rest. It is preferably filled into pipettes and rested at a temperature of 22-25°C for 24-30 hours and then the hydrogels taken out of the pipettes are cut in 3-4 mm sizes and shaped (104).
The shaped polymeric hydrogels are finally washed with double-distilled water and dried in a drying oven (105). In one embodiment of the invention, the polymeric hydrogels that are obtained have a composite structure by means of their clay content. Thus, physical, mechanical and biological features thereof are improved. Hydrogels are cross- linked hydrophilic polymers which can take in a substantial amount of water, and when mixed with clay, a new class of composite material is formed. In the composite polymeric hydrogel of the present invention, the ability of clay adsorbing different components and the elasticity and permeability features of the polymeric hydrogel structure are combined in one body. Thus, swelling ability and thermal and mechanical stability of the hydrogel are enhanced.
When the polymeric hydrogels produced with the method (100) of the present invention are used in controlled drug release, they enable release of the drug in different periods of time. Drug-polymer interaction analysis of the hydrogel of the present invention was also performed and it was observed that it is suitable for clarithromycin active ingredient.
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