• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    Prostacyclin and prostacyclin derivatives form inclusion complexes with cyclodextrins. The complexes may be prepared by contacting an aqueous solution of the cyclodextrin with prostacyclin or a derivative thereof, preferably in organic solvent solution. The inclusion complexes have an improved stability, especially in aqueous solution, compared to the uncomplexed compounds and are extremely potent in inhibiting thrombus formation and inducing the disaggregation of thrombi already formed. The complexes can be formulated into pharmaceutical compositions in conventional manner.
    公开号:SU847914A3
    申请号:SU782668853
    申请日:1978-09-22
    公开日:1981-07-15
    发明作者:Сейтли Йожеф；Сейтли Магдолна；Чех Дьердь；Штадлер Иштван
    申请人:Хиноин Дьедьсер Еш Ведьесети Термекекдьяра,Pt(Инопредприятие)；
    IPC主号:
    专利说明:

    (54) METHOD FOR OBTAINING COMPLEXES OF INCLUSION WITH fb-- CYCLODEXTRIN DERIVATIVES The invention relates to methods for producing inclusion complexes of | b-cyclodextrin derivatives of tacyclines of general formula I and 5Ni, where R is hydrogen or lower alk having pharmacological identity. A known method for producing p glandin X of the formula -.- ,. .dgHij, it is 6n in that the endop of the formula - - COOH HE is subjected to acidic hydrolysis of PROSTACYCLINES. The purpose of the invention is to expand the range of pharmacologically active prostacyclin derivatives. According to the invention, a method for the preparation of inclusion complexes with Jb-cyclodextrin of prostacyclin derivatives of general formula 1 is described, which consists in adding a solution of a prustycline derivative of general formula 1 to a phosphate-containing buffer with pH 7.5-8.5 organic solvent —Grost ether, the solution of I-cyclodextrin contains 15-35 mol))) -cyclodextrin per liter, and the prostacyclin solution 0.5-15 mol of prostacyclin derivative per liter at a molar ratio crystals from 5: 1 to 10: 1, after which the desired products are isolated. Diethyl ether is preferably used as an organic solvent. The most preferred inclusion complexes of this method are complexes with prostacyclin derivatives of general formula 1, where R is hydrogen or methyl.
    Inclusion complexes with α-cyclodextrin derivatives of prostacyclin. The general formula 1 is substantially more stable and has a longer duration of action than free prostacyclin derivatives. These complexes can be used as effective drugs in the presence of blood clots and to prevent their formation.
    Example 1. K1 ml of phosphate buffer solution at pH-8 was added 6 ml of distilled water. 190 mg (L-cyclodextrin (water content 14%)) is dissolved in a solution heated to 30 ° C. After complete dissolution, a solution of 8 mg of prostaglandin X in 31 ml of ether is introduced into the solution with constant stirring. the ether is distilled off at a slight discharge. After complete distillation of the ether, the mixture can be cooled to room temperature with constant stirring (approximately
    1h) Then the solution is frozen and lyophilized in the usual way. The weight of the dried prostacyclin-b-cyclodextrin complex is 182 mg. The complex is a white, amorphous, easily soluble powder in water.
    Example 2. 10 mg of prostacyclin methyl ester is dissolved in
    2 ml diethyl ether. Solution The mixture is added to a mixture consisting of 1 ml of phosphate buffer with a pH of 8 and 5.5 ml of distilled water, in which 200 mg of anhydrous 5B-cyclodextrin is dissolved at 30-C. The mixture was stirred at low temperature for 1 h and then shaken at room temperature for 2 h and the solution was frozen and lyophilized. 198 mg of prostacyclin methyl ester-p-cyclodextrin complex is obtained in the form of an amorphous, white, water-soluble powder, which decomposes when heated without melting.
    权利要求:
    Claims (4)
    [1]
    Invention Formula
    1, Method for preparing inclusion complexes with p-cyclodextrin derivatives of prostacyclins of formula 1
    From the UN
    5H, 1
    he he
    where R is hydrogen or lower alkyl, characterized in that a solution of a prostacyclin derivative of general formula 1, where R is jiMseT is a reduced value, is added to a phosphate buffer containing pH 7.58, an aqueous solution of p, α-cyclodextrin, and an organic solvent ether, the β-cyclodextrin solution contains 15-35 mol of p, α-cyclodextrin per liter, and the prostacyclin solution 0.5-15 mol of the derivative. prostacyclin per liter with a molar ratio of both components ranging from 5: 1 to 10: 1, after which target products are isolated.
    [2]
    2. The method according to claim 1, characterized in that diethyl ether is used as an organic solvent.
    [3]
    3. Method according to paragraphs. one
    and 2, o tl l ichto R means that, em em.
    [4]
    4. Method according to paragraphs.
    1 and 2, that is, R is methyl.
    Sources of information taken into account in the examination
    1. Corey E. |. et a1. Synthesis of Vanes Prostag I andins, X. 1. Amer Chem. Soc. 1977, 99, 2006.
    类似技术:
    公开号 | 公开日 | 专利标题
    CA1309087C|1992-10-20|Cyclodextrin clathrates of carbacyclin derivatives and their use as medicinal agents
    US5196406A|1993-03-23|Cyclodextrin complex of fumagillin derivative
    JPH0662634B2|1994-08-17|Therapeutically active compound
    JPH0742351B2|1995-05-10|Method for producing water-soluble cyclodextrin polymer substituted with ionic group
    JP2706090B2|1998-01-28|3-Unsaturated alkylcephems from 3-trifurylcephems
    JP2636847B2|1997-07-30|Diacetyl line salts and their use in the treatment of arthritis
    SU847914A3|1981-07-15|Method of preparing inclusion complexes with beta-cyclodextrine of prostacycline derivatives
    JPH0764808B2|1995-07-12|Novel 9-halogen prostaglandins and their manufacturing method
    IE47304B1|1984-02-22|Prostaglandin i2 derivatives and process for their production
    FR2626003A1|1989-07-21|CEPHALOSPORIN SALTS, MIXTURES CONTAINING SUCH SALTS AND PROCESS FOR THE PREPARATION OF SULFURIC ACID ADDED SALT
    RU2506258C2|2014-02-10|Method of obtaining activated esters
    CZ293041B6|2004-01-14|Neuraminic acid compounds
    US20040077850A1|2004-04-22|Method for preparation of cefuroxime axetil
    Xi et al.1991|Synthesis of furo [2, 3-c] pyran-β-d-nucleosides by radical-cyclization & their conformational analysis by 500 mhz 1h-nmr spectroscopy
    HU191150B|1987-01-28|Process for producing new prostacycline derivatives
    EP0499322A1|1992-08-19|alkyloxyalkyl derivatives of cyclodextrins
    KR910004585A|1991-03-29|1,5-benzothiazepine derivative and preparation method thereof
    US4330553A|1982-05-18|7-Oxo-PGI2 -derivatives and process for the preparation thereof and pharmaceutical compositions containing same
    IL33226A|1973-10-25|Omega-nor and omega-homo pgf2beta derivatives and process for their preparation
    JP6871942B2|2021-05-19|Method for producing sodium epoprostenol with improved stability
    HU184735B|1984-10-29|Process for preparing new prostaglandin derivatives of the 6-oxo-pge down 1 series
    JP3473949B2|2003-12-08|Tetrahydrofuran phosphate and hydroxyester as prodrugs for corresponding antifungal agents
    US2853497A|1958-09-23|6, 8-bis | 5-hydroxycaprylic acids and delta-lactones thereof
    KR102376668B1|2022-03-21|Method for preparing epoprostenol sodium with improved stability
    JP2000248258A|2000-09-12|Gelling agent comprising sugar derivative having metal coordination ability
    同族专利:
    公开号 | 公开日
    IL55569D0|1978-12-17|
    SE447574B|1986-11-24|
    DE2840142A1|1979-04-05|
    CS200242B2|1980-08-29|
    GB2006193B|1982-05-26|
    FR2404006B1|1981-07-31|
    JPS5456685A|1979-05-07|
    CH637388A5|1983-07-29|
    FI782878A|1979-03-24|
    FR2404006A1|1979-04-20|
    GR65001B|1980-06-12|
    FI65912B|1984-04-30|
    IT7869160D0|1978-09-19|
    DD138600A5|1979-11-14|
    SE7809946L|1979-03-24|
    IL55569A|1981-12-31|
    YU220678A|1983-10-31|
    PL121664B1|1982-05-31|
    NL7809643A|1979-03-27|
    ATA677478A|1982-05-15|
    DK420778A|1979-03-24|
    BE870646A|1979-01-15|
    IT1160661B|1987-03-11|
    HU179141B|1982-08-28|
    FI65912C|1984-08-10|
    PL209773A1|1979-06-04|
    GB2006193A|1979-05-02|
    AT369362B|1982-12-27|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    JPS503362B1|1970-06-10|1975-02-04|
    US3953435A|1974-01-10|1976-04-27|Ono Pharmaceutical Company|Aldehyde derivatives of prostaglandins|
    JPS5395958A|1977-01-31|1978-08-22|Ono Pharmaceut Co Ltd|Prostaglandin analogues and process for their preparation|
    US4178367A|1977-02-21|1979-12-11|Ono Pharmaceutical Co. Ltd.|Prostaglandin I2 analogues|
    JPS53136513A|1977-05-06|1978-11-29|Ono Pharmaceut Co Ltd|Stabilization of prostaglandin-x-related compounds|JPS53136513A|1977-05-06|1978-11-29|Ono Pharmaceut Co Ltd|Stabilization of prostaglandin-x-related compounds|
    US4352793A|1979-04-26|1982-10-05|Sumitomo Chemical Company, Limited|Pharmaceutical composition comprising bencyclane fumarate and cyclodextrin|
    JPS5920230A|1982-07-19|1984-02-01|Ciba Geigy Ag|Drug containing piruprophen|
    JPH0566929B2|1985-06-17|1993-09-22|Teijin Ltd|
    DE3608088C2|1986-03-07|1995-11-16|Schering Ag|Pharmaceutical preparations containing cyclodextrin clathrates of carbacyclin derivatives|
    DE3740838A1|1987-11-27|1989-06-08|Schering Ag|CYCLODEXTRINCLATHRATE OF 5-CYANO-PROSTACYCLINE DERIVATIVES AND THEIR USE AS MEDICINAL PRODUCTS|
    CA2553573A1|2004-01-29|2005-08-11|Eisai R & D Management Co., Ltd.|Method for stabilizing macrolide compound|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    HU77CI1770A|HU179141B|1977-09-23|1977-09-23|
    [返回顶部]