• 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:
    This invention relates to new stable sulpho-adenosyl- L-methionine (SAMe) salts and the relative production process. Said salts have the following general formula: where m can be zero or 1; n is 1.5 when p is 2, and is 3 when p is 1; R is chosen from the group consisting of alkyl, phenylalkyl and carboxyalkyl, in which the linear or branched alkyl chain contains from 8 to 18 carbon atoms. In particular, the salts according to the present invention are SAMe salts of sulphonic acids, or of sulphuric acid esters, or of dioctylsulphosuccinic acid, which fall within formula (I). The process for producing said salts consists of: a) enriching the starting yeast with SAMe; b) lysing the cells and recovering an aqueous solution rich in SAMe (cell lysate); c) purifying the lysate by ultrafiltration; d) precipitating the SAMe by treatment with one of the aforesaid acids or esters; e) separating the precipitated product, washing it and drying it under vacuum.
    公开号:SU1487816A3
    申请号:SU85
    申请日:1985-05-15
    公开日:1989-06-15
    发明作者:Геннари Федерико (It)
    申请人:Bioresearch Spa；
    IPC主号:
    专利说明:

    The invention relates to chemical-pharmaceutical disinfection and relates to methods for the preparation of sulfo-adenosyl-K-m ethionine salts. The aim of the invention is to simplify the method. The method is carried out by mixing acetylacetate, water and yeast, the invention relates to methods for producing a drug, namely, sulfo-adenosyl-a {- salts. methionine chemical and pharmaceutical industry.
    The purpose of the invention is to simplify the method of obtaining salts of sulfo-adenosyl · "(-methionine.
    Note 1. Obtaining the sodium salts of the sulfonic acid of the formula KNW ^ Ma
    80 liters of distilled water, 10 liters of 95% ethanol and 10 liters of n-butanol are added to 20.7 kg (100 mol). 1-bromo Tetra-Cecan. Anhydrous sodium sulfate is added in an amount of G3.9 kg. Po2
    enriched with sulfo-adenosyl-C / -methionium (CAM) of the formula (CAM) n E (O / n (5O 3 H) p ^ where ha is 0 or 1; η = 1.5, if p = 2, η = 3 if p = 1; K. is selected from the group including alkyl, phenyl alkyl, carboxyalkyl, where the alkyl and branched alkyl chain contains 8-18 carbon atoms, sulfuric acid is added, the mixture is subjected to ultrafiltration on membranes with a nominal limit of 10,000, precipitated CAM using sulphonic acid or sulfuric acid esters, or dioctylsulfo-succinic acid with the molar ratio of the specified agent and CAM 3: 1 to 3.5: 1, precipitated washing product t, dried at 40 ° C and residual pressure of 0.5 mm Hg When the method excludes a number of steps associated with the isolation and purification in the preparation of the desired product.
    The mixture is heated by refluxing for 5 days.
    After enrolling the reaction, the mixture obtained is diluted with 300 liters of distilled water, and then heated until complete dissolution. The resulting crystallization product overnight at 15 ° C.
    The tetradecansulphonic acid sodium salt thus obtained is filtered off, washed with 50 liters of distilled water and then 50 liters of acetone in an excess amount. · '
    The resulting product is suspended in 50 l of acetone, heated to 50 ° C.
    Memory ,,, 1487816 A 5
    3
    four
    '148781
    carrying out the extraction of myristyl alcohol, which was formed during the reaction. The mixture is then cooled and the product is filtered off. The resulting product is washed with acetone and dried under vacuum.
    The result is 24 kg of sodium tetradecansulphonic acid (82X) in the form of a white crystalline powder, the solubility of which in water is 1% at 40 ° C while obtaining a pure colorless solution.
    Calculated C 56; H 9.7; 8 10.7. 15
    С ^ Н ^ дДНЯПа
    Found,%: C 56; II 9.6; 5 10.6 / 4.
    Using 1-broshdodecane in the amount of 24.5 kg and conducting the process in accordance with the procedure similar to the 20 • described, 21.7 kg of the sodium <dodecansulphonic acid salt are obtained.
    Using 1-bromhexadecane in the amount of 30.5 kg, 26.3 kg of sodium salt of hexadecanesulfonic acid are obtained, 25 lots.
    Using 1-bromooctadecane in the amount of 33.3 kg, sodium octadecan sulfonic acid is obtained in the amount of 28.5 kg. thirty
    Example 2. Preparation of sulfoadenosyl-sb-methionine 3-hexadecan sulfonate (816).
    220 l of acetylacetate and 220 l of water are added at ambient temperature to 1800 kg of yeast, enriched with sulfo-adenosyl-c / -methionine in the amount of 6.88 g / kg according to the Schlenk technique, Enzymology, 1965, 29.283 ^ 1
    After intensive mixing for! 30 l add 1000 l 0.35 n. sulfuric acid and the mixture is stirred for another 1.5 hours
    The resulting mixture is filtered through a rotary filter, washed with water, and 2800 l of a solution containing 4.40 g / l of sulfo-adenosyl-c4-methionine, equivalent to 99.57, is present, the amount that was present in the starting material.
    The resulting solution of sulfo-adenosyl-o (methionine at pH 2.5 is directed to an ultrafiltration unit which utilizes the tubular Membe x wound with a nominal limit of 10000. ^ 5
    The material that has penetrated through the membranes collects the containers, and the concentrate is sent continuously to recycling to
    6
    obtain a final volume of 200 liters. At this point, distilled water is added and the process retsiklirova- 1 Nia continued until complete extraction sulpho-adenosyl-e / -metianina. The result is 3500 l of ultrafiltered lysate containing 12.2 kg of sulfo-adenosyl-o / -methionine ion.
    35 kg of sodium hexadecanesulfonate are dissolved separately in * 2500 l of deionized water at 50 ° С and 6 kg of concentrated sulfuric acid are added.
    The resulting solution is added to the cell lysate, and a precipitate immediately forms. The resulting mixture is cooled to 20 ° C and stirred for 30 minutes. The precipitate formed is filtered off using a filter press and washed with 300 l of distilled water.
    This product is dried in a vacuum dryer at 40 ° C and a residual pressure of 0.5 mm Hg. until the residual moisture content in the product is less than 1%.
    The result is 37 kg of white powder of the following composition, ”:
    Sulfo-adenosyl-οί ”methionine 30.2
    Hexadecan sulfonic acid 69.6
    Water 0,2
    This composition corresponds to the salt of 3-hexadecan sulfonate sulfo-adenosyl - </ - methionine.
    | The product is obtained as a white powder, insoluble, in water and poorly soluble in methanol, ethanol and acetone. The powder is soluble in a mixture consisting of methanol and chloroform in the ratio of 2: 1, up to 5% at 25 ° C with the formation of a colorless solution.
    The analysis carried out by chromatography in thin layers and carried out in accordance with the procedure described in Apa1, WosNesh, 1 1971, 4,16-28, showed that the product. does not contain any impurities.
    . Calculated, And 6.4; C 57.4;
    H 9.4.,
    - ss and n 34
    • Found ', * ’: M 6.4; C 57.3; H 9.4,
    Analysis of the ultraviolet spectrum of the obtained product (3 mg in 100 ml of a mixture consisting of water and methanol
    five
    148781 ,
    6
    in a 1: 1 ratio, showed the presence of an absorption maximum at 259 nm with E, * = 106.7.
    Example Preparation of sulfo-adenosyl-g / methionine 3-octadecan sulfonate (518).
    The process is carried out analogously to example 2 and receive 3500 ml ultrafilter.
    • in ana- lyse atomic, which contains 12.2 kg of the sulfo-adenosyl-o1-methionine ion.
    Oktadekansulfonat sodium in an amount of 38 kg was dissolved in 3400 liters of deionised water at 50 C and then added to 6 kg of concentrated sulfuric acid. Using techniques; in example 2, get 40 kg of white powder. The product has the following composition
    Sulfo-adenosyl-L-methionine 28.5
    Octadecan sulfonic acid 71.3
    Water 0,2
    The specified composition corresponds
    salts of sulfo-adenosyl-c (-methionine 3-octadecanesulfonate. This product is obtained as a white powder, insoluble in water, as well as methanol, ethanol, acetone.
    The product is soluble in a mixture consisting of methanol and chloroform in a 1: 1 ratio, up to 5% at 20 ° С with the formation of a colorless solution as a result. The analysis carried out by chromatography in thin layers and carried out in accordance with the procedure described in Ap1, Bros., 1971, 4,16-28, showed that the product does not contain any impurities.
    Calculated 7: V 6,0; C, 59.71;
    H 9.7.
    With 1 H g1 ^ O, 5-ZS 1y N 39 O 5 5
    Found,%: K 6,1, C 59,2; H 9.7.
    Analysis of the ultraviolet spectrum of the obtained product (3 mg in 100 ml of a mixture consisting of 10% chloroform, 60% methanol and 30% water) showed the presence of an absorption maximum at a wavelength of 259 nm with KGS | k = 100.3.
    PRI me R 4. Obtaining sulfoadenosyl- ((-methionine 3-tetradecansulphonate (514).
    The process is carried out analogously to example 2 and receive 3500 l of ultrafiltered lysate, which contains
    12.2 kg sulfo-adenosyl-o ion (-methionine.
    Sodium tetradecansulfonate in an amount of 32 kg is dissolved in 200 l of deionized water at 50 ° C and then 6 kg of concentrated sulfuric acid are added.
    Using the method of example 2, get 34 kg of white powder, which according to the analysis has the following composition,%:
    Sul pho-adenosyl- 1 methionine 32.3
    Tetradecan sulfonic acid 67.5
    Water 0,2
    The specified composition corresponds to the salt of sulfo-adenosyl-c! -Metxnine
    20 3-tetradecansulphonate.
    The product is obtained in the form of a white powder, insoluble in water and soluble in methanol or ethanol up to 5% with the formation of a colorless solution. The analysis carried out by chromatography in thin layers and carried out in accordance with the procedure described in Ap1, Worth 1971, 4.16-28, showed that the product does not contain any impurities.
    Calculated,%: V 6,8; From 55.6; ·
    H 9.1.
    С ίί Η · 30, „(), 5
    35 % found: M 6.8; C 55.5; H 9.2. Analysis of the ultraviolet spectrum of the obtained product (3 mg per 100 ml
    • a mixture consisting of water and methanol in a 1: 1 ratio) showed the presence of
    40 maximum absorption at a wavelength of 259 nm with E = 114.
    Example 5. Preparation of sulfoad enosyl-o (-methionine 3-dodecansulphonate (812).
    45 The process is carried out analogously to example 2 and 3500 l of ultrafiltered lysate containing 12.2 kg of sulfo-adenosyl-e / -methionine ion are obtained.
    The pH is adjusted to 6 by
    50 add 2 n sodium hydroxide. A column containing 200 liters of Amberlite C050 resin in the H + form is prepared and washed thoroughly with water.
    55 The obtained lysate is passed through a column filled with the specified resin at a feed rate of 600 l / h and this speed is kept constant throughout the procedure. Further
    7
    eight
    1487811
    200 liters of distilled water are successively passed through the column,
    400 liters of acetic acid with a concentration of 0.1 M and 200 liters of distilled water, Sulfo-adenosyl-L-methionone, are eluted with 500 liters of 0.25 n. sulfuric acid.
    500 l of the eluate is obtained, which contains 11.5 kg of the sulfo-adenosyl ~ s -Methionine ion.
    Dodecane sulfonate in the amount of
    23.5 kg are dissolved in 1000 l of deionized water at 40 ° C and then concentrated acid ^ 5 is added in the amount of 4.5 kg.
    The resulting solution is added to the eluate containing sulfo-adenosyl ~ o (-methionine, and a precipitate immediately forms, 20
    The resulting mixture is cooled to 0 ° C and perematiut within 30 minutes.
    The resulting residue is filtered with a filter press and washed with 300 ml of distilled 25 water. Next, the residue is dried in a vacuum dryer at 40 and a residual pressure of 0.5 mm Hg. until the residual moisture content in the resulting product is less than 30% or more than 1%.
    Get 30.3 kg of white powder of the following composition,
    Sulfo-adenosyl - </ methionine 34.6 ^ 5
    Dodecansulfonate 65.2
    Water 0,2
    This composition corresponds to the salt of sulfo-adenosyl-o -Methionine 3-dodeud cansulfonate. ·
    The product is obtained in the form of a white powder, insoluble in water and soluble in methanol, ethanol, and isopropanol up to 5% with the formation of a colorless solution.
    The analysis carried out by chromatography in thin layers and carried out in accordance with the method described in APA1. Bye
    1971, 4.16-28, showed that the product does not contain any impurities.
    Calculated, / : And 7.3; C 53.3;
    H 8.7.
    C (, 0 58 "ZS SCHN. 2. ^ 0 ^ 3
    Found, ( / : VI 7.4; C 53.3; H 8.8.
    Analysis of the ultraviolet spectrum obtained product (3 mg in 100 ml of a mixture consisting of water and methanol
    45
    55
    in a 1: 1 ratio, showed the presence of an absorption maximum at a wavelength of 259 nm with E ί <% = 1 22.3.
    PRI me R 6. Preparation of sulfoadenosyl-yA-methionine 3-lauryl sulfonate (8012).
    The process is carried out analogously to example 5 and receive 500 l of eluate containing 11.5 kg of ion sulfo-adenosyl -Methionine.
    According to this example, 27.7 kg of industrially produced 90 / sodium lauryl sulfate υ.δ.Ρ. dissolved in 500 ml distilled-. 1 of water, and then add 4.5 kg of concentrated sulfuric acid.
    According to the method described in example 5, get 30,6 white powder 5 which according to the analysis has a barely following composition,%:
    Sulfo-adenosylmethionine 33.3
    Lauryl sulfonic acid 66.5
    Water 0,2
    The composition indicated corresponds to the sulfo-adenosyl-β-methionine 3-lauryl sulfate salt.
    The product is obtained as a white powder, insoluble in water and soluble in methanol and ethanol up to 5 / to form a colorless solution.
    The analysis carried out by chromatography in thin layers and carried out in accordance with the method described in APA1. ViosNesh, 1971, 4, 16-28, showed that the product does not contain any impurities.
    Calculated,%: V 7,0; C, 51.2;
    H 8.4.
    C 15 L ‘ZS-, 1 N, C Od 8
    Found, ’: and 7.0; C 51.3, H 8.3.
    Analysis · ultraviolet spectrum of the obtained product (3 mg in 100 ml of a mixture consisting of water and methanol in the ratio 1: 1) showed the presence of absorption peak at a wavelength of 259 nm with E g <th = 117.4.
    Example 7. Preparation of sulfoad enosyl-U-methionine 3-dodecylbenzenesulfonate (SG 12).
    The process is carried out analogously to example 5 and receive 500 ml of eluate containing 11.5 kg of sulfo-adenosyl-4! -Methionine ion.
    In accordance with this example
    35.5 kg industrially produced
    9
    1487816
    ten
    £ 85 of sodium dodecylbenol sulfonate is dissolved in 600 liters of deionized water, and then concentrated sulfuric acid is added in an amount
    4.5 kg sodium dodecylbenzenesulfonate - a mixture consisting of sodium alkylbenzenesulfonates having the following average compositions,%: C 70 5;
    C 45-50; 35; C 10-15,
    less than 0.05, which corresponds to the empirical formula
    S, e N go O and 8Na.
    Using the method of example 5, get 35 kg of powder slightly yellow color, which according to the analysis has the following composition:
    Sulfo-ad enosyl-ι / methionine thirty Dodecylbeneolsul phacid 69,8 Water 0.2. The specified composition corresponds
    salts sulfo-adenosyl - </ - methionine 3-dodecylbenzene sulfonate.
    The product is obtained in the form of a yellow powder, insoluble in water and soluble in methanol and ethanol up to 5% with the formation of a clear solution.
    The analysis carried out by chromatography in thin layers and carried out in accordance with the method described in APA1; ViosNesh, 1971, 4, 16-28, showed that the product does not contain any impurities.
    Calculated, / : And 6.1; C 60.2;
    H 8.1
    β γί Η 2 ^ Ο 5 8 · 3ί β π „0.8
    Found,%: And 6.2; C 60.1; H 8.1.
    Analysis of the ultraviolet spectrum of the obtained product (3 mg in 100 ml of a mixture consisting of water and methanol in a 1: 1 ratio) showed the presence of an absorption maximum at a wavelength of 259 nm with E 109.
    Example Preparation of sulfoadenosyl-βί-methionine 3-dioctyl sulfo: succinate.
    Analogously to Example 5, ^ 500 l of an eluate containing 11.5 kg of the sulfo-adenosyl - </ - methionine ion is obtained.
    38.5 kg of industrially produced sodium salt of dioctyl sulfosuccinate is dissolved in 2000 l of deionized water at 40 ° C and
    then add concentrated
    sulfuric acid in the amount of 4.5 kg.
    Continuing the process is similar
    example 5 get 43.5 kg of white
    powder of the following composition,%:
    Sulfo-adenosyl-amethionine 24
    Dioctyl sulfosuccinic acid 75.8
    Water 0,2
    This composition corresponds to salt
    sulfo-adenosyl- <7-methionine 3-dioctylsulfosuccinate.
    The product is obtained as a white porcine, insoluble in water and soluble in methanol and ethanol up to 5% with the formation of a colorless transparent solution.
    The analysis carried out by chromatography in thin layers and carried out in accordance with the method described in APA1. No,
    1971, 4, 16-28, showed that the product does not contain any impurities.
    Calculated, ^: And 5.0; C, 54.1;
    H 8.2.
    С, 5 Н ^ 4 О 5 8. ЗС 1в Н 3 , 0 7 8
    Found X: V 5,1; C, 54.1; H 8.3.
    An analysis of the ultraviolet spectrum of the product obtained (3 mg in 100 ml of a mixture consisting of water and methanol at a ratio of 1: 1) showed the presence of an absorption maximum at a wavelength of 259 nm with E t = 84.4.
    PRI me R 9. Obtained with> lfoadenoyl-o (-methionine 3-undecansulphonate.
    The process is carried out analogously to example 5 and receive 500 l of eluate containing 11.5 kg of the ion sulfo-adenosyl - (/ methionine.
    In accordance with this example, sodium uvdecansulphonate in the amount of
    22.5 kg are dissolved in 500 mp of water at 40 ° C, and then 4.5 g of concentrated sulfuric acid are added.
    Using the technique described in. Example 5, get 29 kg of white powder of the following composition, / :
    Sulfo-adenosyl-o / methionine 36
    Undecane sulfonic acid 63.8
    Water 0,2
    This composition corresponds to the salt sulfo-adenosyl-e (-methionine 3-undecansulphonate.
    1487816 '
    I 2
    The product is obtained in the form of a white threshold, insoluble in water and soluble in methanol and ethanol up to 10% with the formation of a colorless transparent solution.
    The analysis carried out by chromatography in thin layers and carried out in accordance with the method described in APA1. No,
    1971, 4, 16-28, showed that the product does not contain any impurities.
    Calculated,%: V 7,6; C, 52.1;
    H 8.5.
    Found,%: And 7.6; C, 62.2; H 8.6.
    Analysis of the ultraviolet spectrum of the obtained product (3 mg in 100 ml of a mixture consisting of water and methanol in the ratio 1: 1) showed the presence of an absorption maximum at a wavelength of 259 nm with 1 <νι = 127.
    I'll try it on. Preparation of sulfoad enosis il - </ - methyonin 3-dec antisulfonate.
    According to the procedure described in example 5, 500 l of an eluate containing 11.5 kg of sulfo-adenosyl-4-’methionine ion is obtained.
    In accordance with this example, sodium decanesulfonate in the amount of
    21.5 kg are dissolved in 400 l of deionized water at 40 ° C and then 4.5 kg of concentrated sulfuric acid is added. Continuing the process as in example 5, get
    26.6 kg of white powder, which according to the analysis has the following composition,%:
    Sulfo-adenosyl-οί methionine 37.5
    Decane sulfonic acid 62.3
    Water 0,2
    The specified composition corresponds to the salt of sulfo-adenosyl-4-methionine 3-decanesulfonate.
    The product is obtained in the form of a white threshold, insoluble in water and soluble in methanol and ethanol up to 10% with the formation of a pure colorless solution. The analysis carried out by chromatography in thin
    layers and carried out in accordance with the methodology described in APA1. WcNet, 1971, 4 "16-28, showed that the product does not contain any impurities.
    Calculated,%: V 7,9; C 50.8;
    H 8.3.
    S 1u N 21 M 4 O / 1 · ZO, O N gg O 8 _ Found,%: And 7.8; C 50.7; H8.2. The analysis carried out to determine the ultraviolet spectrum of the obtained product (3 mg per 100 mp of a mixture consisting of water and methanol in a 1: 1 ratio) showed the presence of an absorption maximum at a wavelength of 259 nm with E 1% = 132.
    The proposed method in comparison with the known excludes a number of stages associated with the isolation and purification upon receipt of the target product, which simplifies the preparation of sulfo-adenosyl-4-methionine salts.
    权利要求:
    Claims (1)
    [1]
    Claim
    The method of obtaining sulfoadenosyl-4-methionine salts by precipitating the target substance in the presence of sulfuric acid, an organic solvent, characterized in that, in order to simplify the process, the yeast sulfo-adenosyl-4-methionine (CAM) of the formula (CAM) η K (0) w ( YAO and N) p, where w-0 or 1; p-1,5, if ”p = 2; n = 3 if p = 1; K is selected from the group consisting of alkyl, phenylalkyl, carboxyalkyl, where the alkyl and branched alkyl chain contains 8-18 carbon atoms, the cells are lyssed by treatment with water and acetylacetate, then with a solution of 0.1-0.5 n. sulfuric acid, the cell lysate is purified by ultrafiltration on membranes with a nominal limit of 10,000, precipitated by CAM using sulfonic acid or sulfuric acid esters or dioctyl sulfosuccinic acid at a molar ratio of said precipitating agent and CAM 3: 1-3.5; 1, the precipitated product is separated, washed it and dried at 40 ° C and a residual pressure of 0.5 mm Hg.
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    IE37913B1|1972-08-02|1977-11-09|Bioresearch Sas|Salt of s-adenosyl-l-methionine|
    IE39517B1|1973-06-27|1978-10-25|Bioresearch Sas|Double salts of s-adenosyl-l-methhionine|
    AR221676A1|1974-07-12|1981-03-13|Bioresearch Sas|PROCEDURE FOR THE PREPARATION OF SULPHONIC AND / OR SULFURIC STABLE SALTS OF S-ADENOSIL-L-METIONINE, PARTICULARLY USEFUL AS SPECIFIC METHYL DONORS FOR THE CH3, ELAMIBLI-TRANSFERRING BIOCHEMICAL AND LATIN-GLOBAL ELEMENTS PROTILICO AND GLUCIDICO|
    JPS53107485A|1977-02-28|1978-09-19|Yamasa Shoyu Co Ltd|Preparation of s-adenosyl-l-methionine salt|
    GB2064523B|1979-12-04|1983-06-29|Kanegafuchi Chemical Ind|Stable composition of s-adenosyl-l-methionine|
    GB2116172B|1982-02-25|1986-07-09|Nippon Zeon Co|Microbial cells containing s-adenosyl methionine in high concentrations and process for production of s adenosyl methionine|
    IT1169773B|1983-08-24|1987-06-03|Bioresearch Spa|PROCESS FOR THE PRODUCTION OF STABLE SALTS OF SULPHO-ADENOSYL-L-METHIONINE|
    JPS60102796A|1983-11-09|1985-06-06|Sanyo Electric Co|Method of connecting terminal of leadless part|
    IT1173990B|1984-05-16|1987-06-24|Bioresearch Spa|STABLE SALTS OF SULPHO-ADENOSYL-METHIONINE PARTICULARLY SUITABLE FOR PARENTERAL USE|IT1173990B|1984-05-16|1987-06-24|Bioresearch Spa|STABLE SALTS OF SULPHO-ADENOSYL-METHIONINEPARTICULARLY SUITABLE FOR PARENTERAL USE|
    IT1177373B|1984-12-06|1987-08-26|Bioresearch Spa|SALTS OF 5'-METHYLLIUM-5'-DEOXYDENOSINE WITH LONG ALCHYLIC CHAIN SULPHONIC ACIDS|
    IT1200589B|1985-02-14|1989-01-27|Gibipharma Spa|NATURAL DERIVATIVES PHARMAGOLOGICAL ACTIVITY|
    AT80165T|1987-10-09|1992-09-15|Vincenzo Zappia|LIPOPHILE SALTS OF S-ADENOSYL-L-METHIONINEWITH ACYLTAURINE DERIVATIVES.|
    GB9211779D0|1992-06-03|1992-07-15|Ciba Geigy Ag|Amine salts|
    WO1994005299A1|1992-09-04|1994-03-17|Fuji Kagaku Kogyo Kabushiki Kaisha|Medicinal composition|
    US6255295B1|1996-12-23|2001-07-03|Nutramax Laboratories, Inc.|Aminosugar, glycosaminoglycan or glycosaminoglycan-like compounds, and s-adenosylmethionine composition for the protection, treatment, repair, and reduction of inflammation of connective tissue|
    US6492349B1|1993-03-31|2002-12-10|Nutramax Laboratories, Inc.|Aminosugar and glycosaminoglycan composition for the treatment and repair of connective tissue|
    IT1317920B1|2000-10-20|2003-07-15|Univ Roma|S-ADENOSYLMETHIONINE AND ITS DERIVATIVES FOR THE TREATMENT AND PREVENTION OF ALZHEIMER DISEASE.|
    US6759395B2|2000-12-18|2004-07-06|Orchid Chemicals & Pharmaceuticals, Ltd.|Soft-gelatin capsule comprising S-adenosylmethionine and a method for producing the same|
    AU2832102A|2000-12-18|2002-07-01|Orchid Chemicals & Pharm Ltd|A novel soft-gelatin capsule comprising s-adenosylmethionine and a method for producing the same|
    US6649753B2|2001-06-07|2003-11-18|Orchid Chemicals & Pharmaceuticals Ltd.|Stable salts of S-adenosyl-L-methionineand the process for their preparation|
    WO2002102823A1|2001-06-14|2002-12-27|Orchid Chemicals & Pharmaceuticals Limited|Stable salts of s-adenosyl-l-methionineand the process for their preparation|
    DK1325740T3|2001-12-12|2004-08-16|Chemistry & Health Int Bv|Stable granules containing s-adenosylmethionine and process for their preparation|
    US20090012036A1|2005-05-24|2009-01-08|Hebert Rolland F|Stable S-adenosyl-L-methionine|
    US20050272687A1|2004-06-08|2005-12-08|Hebert Rolland F|Stable S-adenosyl-l-methionine|
    US8148348B2|2006-01-17|2012-04-03|Mitsubishi Gas Chemical Company, Inc.|Method of stabilizing S-adenosyl-L-methionine and stabilized composition|
    US20090088404A1|2007-01-31|2009-04-02|Methylation Sciences International Srl|Extended Release Pharmaceutical Formulations of S-Adenosylmethionine|
    US20090197824A1|2008-01-31|2009-08-06|Methylation Sciences International Srl|Extended Release Pharmaceutical Formulations of S-Adenosylmethionine|
    AU2008210327B2|2007-01-31|2011-06-16|Methylation Sciences International Srl|Extended release pharmaceutical formulations of S-adenosylmethionine|
    US20100004191A1|2008-07-01|2010-01-07|Rolland F Hebert|Compositions of S-adenosyl-L-methionine.|
    US20110027342A1|2009-07-28|2011-02-03|Msi Methylation Sciences, Inc.|S-adenosylmethionine formulations with enhanced bioavailability|
    US8329208B2|2009-07-28|2012-12-11|Methylation Sciences International Srl|Pharmacokinetics of S-adenosylmethionine formulations|
    KR101748053B1|2012-10-17|2017-06-15|메틸레이션 사이언시즈 인터내셔널 에스알엘|Compositions comprising s-adenosylmethionine and a gallic acid ester|
    KR102186066B1|2013-01-16|2020-12-04|허버트 샘-이 엘엘씨|Stable indole-3-propionate salts of s-adenosyl-l-methionine|
    CN103265595B|2013-05-21|2015-12-23|南京基准生物科技有限公司|The method of S-adenosylmethionine is extracted in a kind of fermentation by saccharomyces cerevisiae liquid|
    法律状态:
    2005-10-10| REG| Reference to a code of a succession state|Ref country code: RU Ref legal event code: MM4A Effective date: 19870516 |
    优先权:
    申请号 | 申请日 | 专利标题
    IT20940/84A|IT1173992B|1984-05-16|1984-05-16|STABLE SALTS OF SULPHO-ADENOSYL-METHIONINEPARTICULARLY SUITABLE FOR ORAL PHARMACEUTICAL USE|
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