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  Clathrate of azithromycin hydrate with 1,2-propyleneglycol, method for the manufacture thereof, and pharmaceutical composition containing sameUSPTO Application #: 20080076725Title: Clathrate of azithromycin hydrate with 1,2-propyleneglycol, method for the manufacture thereof, and pharmaceutical composition containing same Abstract: wherein m ranges from 1 to 2 and n, from 0.30 to 0.45. The present invention relates to a clathrate of azithromycin hydrate with 1,2-propyleneglycol of formula (I), a method for the manufacture thereof, and a pharmaceutical composition containing same. The inventive compound is much less hygroscopic than azithromycin hydrate or crystals known in the art, therefore, it can be useful for the preparation of a medicine for treating various microbial infections. (end of abstract) Agent: - , USPTO Applicaton #: 20080076725 - Class: 514029000 (USPTO) Related Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), O-glycoside, , Oxygen Of The Saccharide Radical Bonded Directly To A Nonsaccharide Hetero Ring Or A Polycyclo Ring System Which Contains A Nonsaccharide Hetero Ring, The Hetero Ring Has 8 Or More Ring Carbons, The Hetero Ring Has Exactly 13 Ring Carbons (e.g., Erythromycin, Etc.) The Patent Description & Claims data below is from USPTO Patent Application 20080076725. Brief Patent Description - Full Patent Description - Patent Application Claims
BRIEF DESCRIPTION OF DRAWINGS [0001] FIG. 1: a powder X-ray diffraction spectrum of the compound of the present invention; [0002] FIG. 2: a powder X-ray diffraction spectrum of azithromycin monohydrate; [0003] FIG. 3: a powder X-ray diffraction spectrum of azithromycin dihydrate; [0004] FIG. 4: a differential scanning calorimetric scan of the compound of the present invention; [0005] FIG. 5: a differential scanning calorimetric scan of azithromycin monohydrate; [0006] FIG. 6: a differential scanning calorimetric scan of azithromycin dihydrate; [0007] FIG. 7: comparative hygroscopic properties of the compound of the present invention, azithromycin anhydride, monohydrate, and dihydrate. DETAILED DESCRIPTION OF THE INVENTION [0008] This invention relates to a novel clathrate of azithromycin hydrate with 1,2-propyleneglycol, a method for its manufacture, and a pharmaceutical composition containing the clathrate. [0009] Azithromycin, 9-deoxo-9a-aza-9a-methyl-9a-homoerythromycin A (N-methyl-11-aza-10-deoxo-10-dehydroerythromycin A: IUPAC) of formula (II) disclosed in U.S. Pat. Nos. 4,517,358 and 4,474,768, is an azalide-type semi-synthetic macrolide antibiotic, useful for treating bronchial infection, sexual contact infection and dermatological infection (see Kirste and Sides; Antimicrob. Agents Chemother., 33, 1419 (1989)). [0010] Azithromycin is known to exist in three forms, the anhydride, monohydrate and dihydrate forms. These forms have been identified by powder X-ray diffraction and differential scanning calorimetric studies, and have different water stabilities. [0011] As disclosed in U.S. Pat. No. 4,517,359, azithromycin anhydride (m.p. 113-115.degree. C.) can be obtained by evaporating solvent (e.g., chloroform) in the course of preparing azithromycin. However, since azithromycin anhydride is non-crystalline product, its highly hygroscopic property is not suitable for pharmaceutical formulation. [0012] Further, azithromycin monohydrate (m.p. 136.degree. C.), as described in U.S. Pat. No. 4,474,768 and WO Publication No. 89/00576, is crystalline but it has also hygroscopic property, making it difficult to maintain its water content at a constant level. [0013] WO Publication No. 89/00576 discloses a process for preparing azithromycin dihydrate (m.p. 126.degree. C.) from azithromycin monohydrate by recrystallizing from a mixture of tetrahydrofuran, water and a C.sub.5.about.C.sub.7 aliphatic hydrocarbon. [0014] Although the dihydrate is less hydroscopic than the monohydrate, the water content thereof must be carefully maintained during a vacuum drying (controlled to be a water content of 4.6%.+-.0.2, and a volatile component content of less than 0.25%) step at a relatively low temperature. Such a water content controlling procedure is, however, not sufficient for removing the toxic aliphatic hydrocarbon solvent such as n-hexane (classified as second grade by ICH (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use)) rigorously used in the recrystallization procedure. On the other hand, vacuum drying in higher temperature may result in formation of azithromycin dihydrate having undesirable water content. Further, the preparation of the dihydrate requires a high production cost. [0015] Accordingly, many attempts have been made to develop a novel crystal or solvate form of azithromycin. For example, EP Publication No. 0,984,020 discloses a clathrate of azithromycin monohydrate with isopropanol of formula (III). [0016] WO Publication No. 00/32203 discloses an ethanol solvate of azithromycin hydrate of formula (IV). [0017] wherein, x is a molar equivalent of water such that the water content can range from 2.0 to 4.0%, and y a molar equivalent of ethanol such that the ethanol content can range from 1.5 to 3.0%. [0018] Further, WO Publication No. 99/58541 discloses a solvate of azithromycin with a non-halogenated solvent, European Patent No, 0,941,999 A and U.S. Pat. No. 5,869,629 discloses a method for preparing azithromycin dihydrate from azithromycin monohydrate using acetone and water. However, there has existed a need to develop an improved crystal form of azithromycin crystal suitable for pharmaceutical applications. [0019] The present inventors have endeavored to develop a novel clathrate of azithromycin having good water-stability, and found that a clathrate of azithromycin hydrate with 1,2-propyleneglycol obtained by dissolving azithromycin in acetone containing 1,2-propyleneglycol and then recrystallizing with water can be prepared at a high yield and be useful for the preparation of a medicine for treating various microbial infections [0020] It is, therefore, an object of the present invention to provide a novel clathrate form of azithromycin, a method for the manufacture thereof, and a pharmaceutical composition comprising same. [0021] In accordance with the present invention, there is provided a novel clathrate of azithromycin hydrate with 1,2-propyleneglycol of formula (I): wherein m ranges from 1 to 2 and n, from 0.30 to 0.45. [0022] The present invention further provides a process for preparing the clathrate of formula (I), comprising the steps of: (1) dissolving azithromycin in acetone then adding 1,2-propyleneglycol and water thereto to obtain a crystalline product; and (2) filtering the crystals formed, washing the crystals with water and drying at 40 to 45.degree. C. for 12 to 24 hours. Continue reading... Full patent description for Clathrate of azithromycin hydrate with 1,2-propyleneglycol, method for the manufacture thereof, and pharmaceutical composition containing same Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Clathrate of azithromycin hydrate with 1,2-propyleneglycol, method for the manufacture thereof, and pharmaceutical composition containing same patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. 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