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1. 发明申请

WO1991000855A1 NOVEL VITAMIN D ANALOGUES 审中-公开
标题翻译：新维生素D类似物
公开(公告)号：WO1991000855A1
公开(公告)日：1991-01-24
申请号：PCT/DK1990000168
申请日：1990-07-04
申请人： LEO PHARMACEUTICAL PRODUCTS LTD. A/S (LOVENS ... , BINDERUP, Ernst, Torndal , CALVERLEY, Martin, John
发明人： LEO PHARMACEUTICAL PRODUCTS LTD. A/S (LOVENS ...
IPC分类号： C07C401/00
CPC分类号： C07F9/117 , C07C401/00
摘要： The present invention relates to compounds of formula (I), in which formula n is 2 or 3, m is 0 or an integer from 1-4; R?1 and R2¿ (which may be the same or different) stand for hydrogen or C¿1?-C8-hydrocarbyl, hydrocarbyl indicating the residue after removal of a hydrogen atom from a straight, branched or cyclic saturated or unsaturated hydrocarbon, or taken together with the carbon bearing the hydroxyl group (starred in formula (I)), R?1 and R2¿ can form a saturated or unsaturated C¿3?-C8 carboxylic ring; in addition, R?1¿ and/or R2 and/or one of the m carbons designated by the ''°'' may be optionally substituted with one or more chlorine or fluorine atom(s); and finally one of the carbons designated ''°'' may optionally be substituted by one or two C¿1?-C2 alkyl groups(s); and derivatives of the compounds of formula (I) in which one or more hydroxy have been transformed into -O-acyl or O-glycosyl or phosphate ester groups; such masked groups being hydrolyzable in vivo. The present compounds find use in both the human and veterinary practice in the treatment and prophylaxis of autoimmune diseases (including diabetes mellitus), hypertension, acne, alopecia, skin ageing, imbalance in the immune system, inflammatory diseases such as as rheumatoid arthritis and asthma as well as diseases characterized by abnormal cell differentiation and/or cell proliferation, such as e.g. psoriasis and cancer.

2. 发明申请

WO1989009775A1 N-HETEROCYCLIC PROPYLIDENE-1,1-BISPHOSPHONIC ACIDS, THEIR PRODUCTION AND A PHARMACEUTICAL COMPOSITION 审中-公开
标题翻译： N-杂环戊二烯-1,1-二磷酸，其生产和药物组合物
公开(公告)号：WO1989009775A1
公开(公告)日：1989-10-19
申请号：PCT/DK1989000071
申请日：1989-03-29
申请人： LEO PHARMACEUTICAL PRODUCTS LTD. A/S (LOVENS ... , BINDERUP, Ernst, Torndal , LIISBERG, Sven
发明人： LEO PHARMACEUTICAL PRODUCTS LTD. A/S (LOVENS ...
IPC分类号： C07F09/56
CPC分类号： C07F9/5728 , C07F9/572
摘要： The present invention relates to compounds of formula (I) in which R1-R8 can be the same or different and stand for hydrogen or a straight or branched aliphatic C1-C10 hydrocarbon radical. In addition, R3 when taken together with either R1 or R5 can form a saturated aliphatic 5-, 6- or 7-membered ring, which may be substituted with one or more C1-C4-alkyl radicals. The present compounds are effective e.g. in drugs influencing calcium metabolism.
摘要翻译：本发明涉及式（I）化合物，其中R 1 -R 8可以相同或不同，代表氢或直链或支链脂族C 1 -C 10烃基。另外，R 3与R 1或R 5一起可以形成可被一个或多个C 1 -C 4 - 烷基取代的饱和脂肪族5-，6-或7-元环。本发明化合物是有效的。在影响钙代谢的药物中。

3. 发明申请

WO1987003598A1 NOVEL BISPHOSPHONIC DERIVATIVES, A METHOD FOR THEIR PRODUCTION AND A PHARMACEUTICAL COMPOSITION 审中-公开
标题翻译：新型双膦衍生物，其生产方法和药物组合物
公开(公告)号：WO1987003598A1
公开(公告)日：1987-06-18
申请号：PCT/DK1986000132
申请日：1986-12-10
申请人： LEO PHARMACEUTICAL PRODUCTS LTD. A/S (LOVENS ... , BINDERUP, Ernst, Torndal , LIISBERG, Sven
发明人： LEO PHARMACEUTICAL PRODUCTS LTD. A/S (LOVENS ...
IPC分类号： C07F09/65
CPC分类号： C07F9/6544 , C07F9/6536
摘要： Novel compounds of formula (I), in which R1-R11 can be the same or different and stand for hydrogen, a straight or branched aliphatic or alicyclic C1-C10 hydrocarbon radical, an aryl or an aryl-C1-C4-alkyl radical; n is zero or one, and m is zero, one or two; or R2 and R4 when taken together form a saturated aliphatic 5-, 6- or 7-membered ring which may be substituted with one or more C1-C4-alkyl radicals; and pharmaceutically acceptable salts and easily hydrolyzable esters thereof, methods for producing said new compounds, pharmaceutical compositions containing the new compounds, dosage units of the compositions, and methods of treating patients using said compositions and dosage units. The present compounds are valuable in the human and veterinary practice by reducing bone resorption and surprisingly also stimulating bone alkaline phosphatase. A substantial increase in bone mass is actually observed during treatment with the present compounds.

4. 发明申请

WO1987000834A1 NOVEL VITAMIN D ANALOGUES 审中-公开
标题翻译：新维生素D类似物
公开(公告)号：WO1987000834A1
公开(公告)日：1987-02-12
申请号：PCT/DK1986000081
申请日：1986-07-14
申请人： LEO PHARMACEUTICAL PRODUCTS LTD. A/S , CALVERLEY, Martin, John , BINDERUP, Ernst, Torndal
发明人： LEO PHARMACEUTICAL PRODUCTS LTD. A/S
IPC分类号： C07C172/00
CPC分类号： C07C401/00
摘要： Vitamin D analogues represented by general formula (I), in which formula X stands for hydrogen, lower alkyl, halogen or hydroxy; Y stands for hydrogen or hydroxy; R and R , which may be the same or different, stand for lower alkyl, optionally substitutedwith halogen or hydroxy with the proviso that R and R cannot both be methyl when X is other than lower alkyl, or, taken together with the carbon atom numbered 25, R and R can form a saturated or unsaturated C3-C9 carbocyclic ring which may optionally be substituted at any possible position(s) with lower alkyl, halogen or hydroxy; R stands for hydrogen or lower alkyl; R and R represent either each hydrogen, or when taken together constitute a bond, with the result that a double bond connects carbon atoms numbered 22 and 23; and bioreversible derivatives thereof. The compounds of the invention have a favourable therapeutic index and are particularly useful in the treatment of human and veterinary disorders which are characterized by abnormal cell proliferation and/or cell differentiation.
摘要翻译：由通式（I）表示的维生素D类似物，其中式X代表氢，低级烷基，卤素或羟基; Y代表氢或羟基; R 1和R 2可以相同或不同，代表低级烷基，任选地被卤素或羟基取代，条件是当X不是二烷基时，R 1和R 2不能都是甲基或者与25号碳原子一起，R 1和R 2可以形成饱和或不饱和的C 3 -C 9碳环，其可任选地在任何可能的位置被低级烷基取代，卤素或羟基; R 3代表氢或低级烷基; R 4和R 5代表每个氢，或者当它们一起构成键时，结果是双键连接22和23的碳原子; 及其生物可逆衍生物。本发明的化合物具有有利的治疗指数，特别可用于治疗以异常细胞增殖和/或细胞分化为特征的人和兽医病症。

5. 发明申请

WO2004037781A1 VITAMIN D ANALOGUES, COMPOSITIONS COMPRISING SAID ANALOGUES AND THEIR USE 审中-公开
标题翻译：维生素D类似物，包含类似物的组合物及其用途
公开(公告)号：WO2004037781A1
公开(公告)日：2004-05-06
申请号：PCT/DK2003/000718
申请日：2003-10-23
申请人： LEO PHARMA A/S , BINDERUP, Ernst, Torndal , HANSEN, Kai, Holst , BRETTING, Claus, Aage, Svensgaard , CALVERLEY, Martin, John
发明人： BINDERUP, Ernst, Torndal , HANSEN, Kai, Holst , BRETTING, Claus, Aage, Svensgaard , CALVERLEY, Martin, John
IPC分类号： C07C401/00
CPC分类号： C07C401/00 , A61K31/59 , A61K31/593
摘要： Compounds according to formula I: in which formula R1 and R2, which may be the same or different, represent halogen, (C 1 -C 6 ) hydrocarbyl, optionally substituted with one or two hydroxyl group on one or more fluorine atoms, or, together with the carbon atom to which they are both attached, R1 and R2 form a (C 3 -C 6 )carbocyclic ring, or one of R1 and R2 taken together with R3 forms a direct bond, such that a triple bond is constituted, or R1 and R2 represent both hydrogen; R3 when not forming a direct bond with one of R1 and R2 represents hydrogen or (C 1 -C3)hydrocarbyl; X represents (E)-ethylene, (Z)-ethylene, ethynylene, or a bond; Y and Z independently represent hydrogen or methyl; the bond between C#16 and C#17 is depicted with a dotted line to illustrate that said bond may be either a single bond, in which case the projection of the ring substituents is beta, or a double bond; A represents hydroxyl, fluorine or hydrogen; B represents CH 2 or H 2 ; the configuration is the 3-position corresponds to the same configuration as in natural vitamine D 3 (normal), or the configuration in the configuration in the 3-position is opposite to that of natural vitamin D 3 (epi); with the proviso that when X represents (E)-ethylene or (Z)-ethylene, one of R1 and R2 taken together with R3 may not form a direct bond, such that a triple bond is constituted; with the further proviso that when X represents a bond R1 ands R2 are nor hydrogen; with the further proviso that the compound of formula I is not 3(S)-hyroxy-9, 10-secocholesta-5(Z),7(E),10(19),22(E),24-penta-ene; and prodrugs and stereo isomeric forms thereof are provided together with their use in therapy, and their use in the manufacture of medicaments.
摘要翻译：根据式I的化合物：其中可以相同或不同的式R 1和R 2表示卤素，（C 1 -C 6）烃基，任选被一个或多个氟原子上的一个或两个羟基取代，或者与它们所连接的碳原子，R 1和R 2形成（C 3 -C 6）碳环，R 1和R 2中的一个与R 3一起形成直接键，从而构成三键或R1和R2 代表氢; 当不与R 1和R 2中的一个直接键合时，R 3表示氢或（C 1 -C 3）烃基; X表示（E） - 亚乙基，（Z） - 亚乙基，亚乙炔基或键; Y和Z独立地表示氢或甲基; 以虚线描绘C＃16和C＃17之间的键，以说明所述键可以是单键，在这种情况下，环取代基的投影为β或双键; A表示羟基，氟或氢; B表示CH 2或H 2; 该配置是与天然维生素D3（正常）相同的配置，或3位置的配置与天然维生素D3（epi）相反的配置; 条件是当X表示（E） - 亚乙基或（Z） - 亚乙基时，R 1和R 2中的一个与R 3一起可以不形成直接键，从而构成三键; 进一步的条件是当X表示键R1和R2不是氢时; 进一步的条件是式I化合物不是3（S） - 羟基-9,10-半胱胆甾-5（Z），7（E），10（19），22（E），24-戊烯 ; 并且其前体药物和立体异构形式与其在治疗中的用途一起提供，以及它们在制备药物中的用途。

6. 发明申请

WO2003097601A1 CYANOGUANIDINE PRODRUGS 审中-公开
公开(公告)号：WO2003097601A1
公开(公告)日：2003-11-27
申请号：PCT/DK2003/000318
申请日：2003-05-15
申请人： LEO PHARMA A/S , BINDERUP, Ernst, Torndal , DUVOLD, Tore
发明人： BINDERUP, Ernst, Torndal , DUVOLD, Tore
IPC分类号： C07D213/02
CPC分类号： C07D213/75 , A61K31/444
摘要： Pyridyl cyanoguanidine compounds of the general formula I wherein A, X 1 , X 2 , X 3 , Y 1 , Y 2 , Y 3 , R 1 , R 2 , R 5 , R 6 and n are as indicated in the description are suitable as prodrugs in human and veterinary therapy of proliferative diseases such as cancers.
摘要翻译：其中A，X 1，X 2，X 3，Y 1，Y 2，Y 3，R 1，R 2，R 5，R 6和n如说明书中所示的通式I的吡啶基氰基胍化合物适合作为增殖性疾病的人和兽医疗法中的前药如癌症。

7. 发明申请

WO0242265A3 CYANOGUANIDINE PRODRUGS 审中-公开
公开(公告)号：WO0242265A3
公开(公告)日：2002-08-15
申请号：PCT/DK0100750
申请日：2001-11-14
申请人： LEO PHARMA AS , BINDERUP ERNST TORNDAL , HJARNAA PERNILL-JULIA VIG
发明人： BINDERUP ERNST TORNDAL , HJARNAA PERNILL-JULIA VIG
IPC分类号： A61K31/196 , A61K31/198 , A61K31/282 , A61K31/337 , A61K31/4422 , A61K31/4425 , A61K31/475 , A61K31/513 , A61K31/675 , A61K31/704 , A61K31/7048 , A61K31/7068 , A61K45/00 , A61P35/00 , A61P35/02 , A61P43/00 , C07D211/84 , C07D213/50 , C07D213/74 , C07D213/75 , C07D217/22 , A61K31/44
CPC分类号： C07D213/75 , C07D211/84 , C07D213/50 , C07D217/22
摘要： The invention relates to compounds of formula (I), wherein X1 and X2 independently represent a bond; a straight, branched and/or cyclic hydrocarbon diradical, optionally substituted with one or more hydroxy, halogen, nitro, amino, cyano, aminosulfonyl, alkylsulfonylamino, alkylcarbonyl, formyl, aminocarbonyl or alkylcarbonylamino; a heteroarylene or non-aromatic heterocyclic hydrocarbon diradical, all of which are optionally substituted with one or more straight, branched and/or cyclic non-aromatic hycrocarbon radical, hydroxyl, halogen, amino, nitro, cyano, aminosulfonyl, alkylsulfonylamino, alkylcarbonyl, formyl, aminocarbonyl or alkylcarbonylamino; Y1 and Y2 independently represent a bond, an ether diradical (R'-O-R''), an amine diradical (R'-N-R''), O, S, S(O), S(O)2, C(O), NH-CO, CO-NH, SO2-N(R'), methylene or N(R')-SO2 wherein R' et R'' independently represent straight or branched hydrocarbon diradicals containing up to 4 carbon atoms; Y3 represents O, O-C(O), C(O)-O, N(R8), R8 being hydrogen or C1-4alkyl; R1 represents hydrogen or straight, branched and/or cyclic alkyl, optionally substituted with phenyl; or an aromatic hydrocarbon radical; R2 represents aryl, heteroaryl or a non-aromatic heterocyclic hydrocarbon radical, all of which are optionally substituted; tetrahydropyranyloxy, di-(C1-4 alkoxy)phosphinoyloxy or C1-4 alkoxycarbonylamino; R3 represents hydrogen; a straight, branched and/or cyclic hydrocarbon radical, optionally substituted with one or more amino, hydroxy, carboxy, halogen, nitro, cyano, alcoxy, aminocarbonyl, C1-4alkoxycarbonyl, C1-4alkoxycarbonylamino, sulfo, hydroxysulfonyloxy, dihydroxyphosphinoyloxy, phosphono, sulfamino, aminosulfonyl, aminoacylamino or dialkoxyphosphinoyl; heteroaryl or a non-aromatic heterocyclic hydrocarbon radical, all of which are optionally substituted with one or more straight, branched and/or cyclic hydrocarbon radical, amino, hydroxy, carboxy, halogen, nitro, cyano, alkoxy, aminocarbonyl, C1-4alkoxycarbonyl, C1-4alkoxycarbonylamino, sulfo, hydroxysulfonyloxy, dihydroxyphosphinoyloxy, phosphono, sulfamino, aminosulfonyl, aminoacylamino or dialkoxyphosphinoyl; (a) wherein s is an integer from 1 to 200; R6 is hydrogen or an optionally substituted non-aromatic hydrocarbon radical; R7 Is independently hydrogen or methyl; R4 and R5 Independently represent hydrogen; a straight, branched and/or cyclic hydrocarbon radical, optionally substituted with halogen, hydroxyl, halogen, amino, nitro or cyano; A represents hydrogen, an optionally substituted, straight, branched and/or cyclic hydrocarbon radical, hydroxy, halogen, nitro, cyano, heteroaryl, heteroaralkyl or thiol; m and r are independently integers from 0 to 4; and n is 0 or 1; Z- is a pharmaceutically acceptable anion, such as chloride, bromide, iodide, sulfate, methanesulfonate, p-toluenesulfonate, nitrate or phosphate. The compounds are well suited as prodrugs in human and veterinary therapy.
摘要翻译：本发明涉及式（I）化合物，其中X 1和X 2独立地表示键; 任选被一个或多个羟基，卤素，硝基，氨基，氰基，氨基磺酰基，烷基磺酰基氨基，烷基羰基，甲酰基，氨基羰基或烷基羰基氨基取代的直链，支链和/ 所有这些都可以被一个或多个直链，支链和/或环状的非芳族羟基羰基，羟基，卤素，氨基，硝基，氰基，氨基磺酰基，烷基磺酰基氨基，烷基羰基，甲酰基，氨基羰基或烷基羰基氨基; Y1和Y2独立地表示键，醚二价（R'-O-R“），胺二价（R'-N-R”），O，S，S（O），S（O）2 ，C（O），NH-CO，CO-NH，SO2-N（R'），亚甲基或N（R'） - SO 2，其中R'和R'独立地表示含有至多4个碳的直链或支链烃基原子; Y 3表示O，O-C（O），C（O）-O，N（R 8），R 8为氢或C 1-4烷基; R 1表示氢或任选被苯基取代的直链，支链和/或环状烷基; 或芳族烃基; R 2表示芳基，杂芳基或非芳族杂环烃基，所有这些都是任选取代的; 二（C 1-4烷氧基）膦酰氧基或C 1-4烷氧基羰基氨基; R3表示氢; 任选被一个或多个氨基，羟基，羧基，卤素，硝基，氰基，烷氧基，氨基羰基，C 1-4烷氧基羰基，C 1-4烷氧基羰基氨基，磺基，羟基磺酰氧基，二羟基亚磷酰基氧基，膦酰基，磺基氨基取代的直链，支链和/或环状烃基氨基磺酰基，氨基酰氨基或二烷氧基膦酰基; 杂芳基或非芳族杂环烃基，它们全部被一个或多个直链，支链和/或环状烃基，氨基，羟基，羧基，卤素，硝基，氰基，烷氧基，氨基羰基，C 1-4烷氧基羰基， C 1-4烷氧基羰基氨基，磺基，羟基磺酰氧基，二羟基磷酰氧基，膦酰基，磺氨基，氨基磺酰基，氨基酰氨基或二烷氧基膦酰基; （a）其中s是1至200的整数; R6是氢或任选取代的非芳族烃基; R7独立地是氢或甲基; R4和R5独立代表氢; 任选被卤素，羟基，卤素，氨基，硝基或氰基取代的直链，支链和/或环状烃基; A表示氢，任选取代的直链，支链和/或环状烃基，羟基，卤素，硝基，氰基，杂芳基，杂芳烷基或硫醇; m和r独立地为0至4的整数; 并且n为0或1; Z-是药学上可接受的阴离子，例如氯化物，溴化物，碘化物，硫酸盐，甲磺酸盐，对甲苯磺酸盐，硝酸盐或磷酸盐。该化合物在人和兽医治疗中非常适合作为前药。

8. 发明申请

WO2006024296A1 EPIMERISATION OF ALLYLIC ALCOHOLS 审中-公开
标题翻译：各种酒精的消除
公开(公告)号：WO2006024296A1
公开(公告)日：2006-03-09
申请号：PCT/DK2005/000533
申请日：2005-08-22
申请人： LEO PHARMA A/S , PEDERSEN, Henrik , BRETTING, Claus, Aage, Svensgaard , BINDERUP, Ernst, Torndal
发明人： PEDERSEN, Henrik , BRETTING, Claus, Aage, Svensgaard , BINDERUP, Ernst, Torndal
IPC分类号： C07C401/00 , C07J9/00
CPC分类号： C07J9/00 , C07C401/00 , C07C2601/02
摘要： The present invention relates to processes for epimerising alcohols of compounds having a hydroxyl substituent on an asymmetric allylic carbon, such as compounds useful for the synthesis of vitamin D analogues where the epimeric hydroxyl substituent is at the 24 position. The invention further relates to methods of producing intermediates useful for the synthesis of calcipotriol by said epimerisation processes.
摘要翻译：本发明涉及在不对称烯丙基碳上具有羟基取代基的化合物的差向异构化方法，例如可用于合成维甲酸类似物的化合物，其中差向异构羟基取代基在24位。本发明还涉及通过所述差向异构化方法生产可用于合成卡泊三醇的中间体的方法。

9. 发明申请

WO1989010351A1 NOVEL VITAMIN D ANALOGUES 审中-公开
标题翻译：新维生素D类似物
公开(公告)号：WO1989010351A1
公开(公告)日：1989-11-02
申请号：PCT/DK1989000079
申请日：1989-04-07
申请人： LEO PHARMACEUTICAL PRODUCTS LTD. A/S (LOVENS ... , CALVERLEY, Martin, John , BINDERUP, Lise , BINDERUP, Ernst, Torndal
发明人： LEO PHARMACEUTICAL PRODUCTS LTD. A/S (LOVENS ...
IPC分类号： C07C172/00
CPC分类号： C07C401/00
摘要： The present invention relates to compounds of formula (I), in which formula, n is an integer from 1-7; and R and R , which may be the same or different, stand for hydrogen, or lower alkyl (but with the proviso that when n = 1, R and R cannot simultaneously be hydrogen, nor can R and R simultaneously be an alkyl group independently chosen from methyl, ethyl and normal-propyl, and when n = 2, R and R cannot simultaneously be methyl), or lower cyclo-alkyl, or, taken together with the carbon (starred in formula I) bearing the hydroxyl group, R and R can form a saturated or unsaturated C3-C9 carbocyclic ring; and R and R represent either simultaneously hydrogen, or when taken together constitute a bond, such that a double bond connects carbons 22 and 23; including diastereoisomeric forms (e.g. E or Z configuration of the 22,23-double bond; R or S configuration at the starred carbona atom) of the compounds of formula (I), in pure form or in mixtures. The present compounds find use in both the human and veterinary practice and show antiinflammatory and immuno-modulating effects as well as strong activity in inducing differentiation and inhibiting undesirable proliferation of certain cells, including cancer cells and skin cells.
摘要翻译：本发明涉及式（I）化合物，其中n为1-7的整数; 和R 1和R 2可以相同或不同，代表氢或低级烷基（但条件是当n = 1时，R 1和R 2不能同时为氢 R 1和R 2也可以同时为独立地选自甲基，乙基和正丙基的烷基，当n = 2时，R 1和R 2不能同时为甲基），或或者与带有羟基的碳（主要配方I）一起，R 1和R 2可以形成饱和或不饱和的C 3 -C 9碳环; 并且R 3和R 4同时代表氢，或者当它们一起构成键时，使得双键连接碳22和23; 包括式（I）化合物的纯粹形式或混合物中的非对映异构形式（例如22,23-双键的E或Z构型;在星形碳原子上的R或S构型）。本发明化合物在人和兽医学实践中都有用，显示出抗炎和免疫调节作用，并且在诱导分化和抑制某些细胞（包括癌细胞和皮肤细胞）的不期望的增殖方面具有很强的活性。

10. 发明申请

WO1988000829A1 PHARMACEUTICAL COMPOSITIONS CONTAINING A BISPHOSPHONATE AND THEIR USE FOR NASAL ADMINISTRATION 审中-公开
标题翻译：含有二磷酸酯的药物组合物及其用于NASAL管理的药物组合物
公开(公告)号：WO1988000829A1
公开(公告)日：1988-02-11
申请号：PCT/DK1987000084
申请日：1987-07-03
申请人： LEO PHARMACEUTICAL PRODUCTS LTD. A/S (LOVENS ... , RASTRUP ANDERSEN, Niels, Smidt , BINDERUP, Ernst, Torndal
发明人： LEO PHARMACEUTICAL PRODUCTS LTD. A/S (LOVENS ...
IPC分类号： A61K31/66
CPC分类号： A61K47/28 , A61K9/0043 , A61K31/66
摘要： Pharmaceutical compositions containing a bisphosphonate or a salt thereof, optionally together with an enhancer for nasal absorption, and their use for nasal administration. The enhancer for the nasal absorption preferably is sodium tauro-24,25-dihydrofusidate (STDF).
摘要翻译：含有双膦酸盐或其盐的药物组合物，任选与鼻吸收用增强剂一起使用，以及用于鼻内给药。用于鼻吸收的增强剂优选为牛磺-24,25-二氢孕芥酸钠（STDF）。

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