Mesalamine thermosensitive gel enema and preparation method thereof

Abstract

The invention discloses a temperature-sensitive gel enema capable of prolonging the detention time of mesalazine in colons and a preparation method of the temperature-sensitive gel enema. The mesalazine temperature-sensitive gel enema is prepared from mesalazine as a main drug, temperature-sensitive gel substrate poloxamer, a bio-adhesive material, a stabilizer and an appropriate amount of water. The mesalazine temperature-sensitive gel enema for colons disclosed by the invention is a liquid freely flowing at a room temperature, is injected to the colons in a liquid form, and has the advantages of uniform drug distribution and good spreadability. Then, the mesalazine temperature-sensitive gel enema is subjected to phase transformation fast under a body temperature condition to form non-chemically-crosslinked semisolid gel, thereby prolonging the detention time of the drug in the colons in addition to the mucous membrane adhesion effect of the bio-adhesive material. Compared with a conventional mesalazine enema, the mesalazine temperature-sensitive gel enema disclosed by the invention can be used for effectively reducing drug liquid leakage and improving the curative effect, and has the advantages of simple preparation and low irritation.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to a mesalamine temperature-sensitive gel enema and a preparation method thereof. Background technique [0002] Ulcerative colitis (Ulcerative colitis, UC) is a chronic non-specific intestinal inflammation whose etiology is not very clear. The lesions are mainly in the colorectal mucosa and submucosa, and can form visible erosions and ulcers. The range of lesions mostly starts from the distal colon and develops reversibly to the proximal end, even involving the entire colon, and occasionally involving the terminal ileum, showing a continuous distribution. The incidence of UC is high in Europe and America, and relatively low in Asian and African countries. In recent years, the number of reported cases in China has gradually increased, and the incidence of UC in my country has shown an upward trend. Since the etiology and pathogenesis of the disease have not yet been elucidat...

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Problems solved by technology

[0009] Bostan et al. crosslinked chitosan and poly-N-isopropylacrylamide, and used the crosslinked product as the gel material to prepare a mesalazine temperature and pH dual-sensitive gel (Bostan MS, et al. Int J Biol Macromol,2013,52:177-83.), this study has not yet involved pharmacodynamics and irritation evaluation, etc. From the perspective of preparation technology, the cross-linking reaction process is complicated, and the organic solvent introduced affects to a certain extent The safety of the preparation

Ramadass et al. used collagen as the gel matrix to prepare mesalamine rectal administration in situ gel, which was also pH and temperature sensitive (RamadassSK, et al. Eur J Pharm Sci, 2013, 48(1-2) :104-10.), due to the poor stability of the carrier material collagen, the gel system must be kept below 10°C, which brings inconvenience to the storage of the preparation

The pH of the above two dual-sensitivity gel systems are both designed at 4~5, and the pH at which the phase transition occurs is 7~8. Due to the very limited buffering capacity of the intestinal tract and the large volume of an enema, the pH of the preparation in actual medication It is difficult to achieve the pH required for phase transition in a short time, so pH sensitivity may be difficult to show

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