CN112915063B - 一种用于治疗子宫平滑肌高频率强直性收缩相关疾病的化合物 - Google Patents
一种用于治疗子宫平滑肌高频率强直性收缩相关疾病的化合物 Download PDFInfo
- Publication number
- CN112915063B CN112915063B CN202110099693.4A CN202110099693A CN112915063B CN 112915063 B CN112915063 B CN 112915063B CN 202110099693 A CN202110099693 A CN 202110099693A CN 112915063 B CN112915063 B CN 112915063B
- Authority
- CN
- China
- Prior art keywords
- compound
- pluronic
- suppository
- parts
- smooth muscle
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 43
- 210000002460 smooth muscle Anatomy 0.000 title claims abstract description 20
- 230000036977 tonic contraction Effects 0.000 title claims abstract description 10
- 201000010099 disease Diseases 0.000 title claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 9
- 239000000829 suppository Substances 0.000 claims abstract description 27
- 239000003814 drug Substances 0.000 claims abstract description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 30
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 28
- 235000011187 glycerol Nutrition 0.000 claims description 12
- 229940057995 liquid paraffin Drugs 0.000 claims description 7
- 239000010687 lubricating oil Substances 0.000 claims description 7
- 238000004806 packaging method and process Methods 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 238000002844 melting Methods 0.000 claims description 4
- 230000008018 melting Effects 0.000 claims description 4
- 238000005303 weighing Methods 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 1
- 238000007711 solidification Methods 0.000 claims 1
- 230000008023 solidification Effects 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 15
- XNOPRXBHLZRZKH-UHFFFAOYSA-N Oxytocin Natural products N1C(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CC(C)C)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(C(C)CC)NC(=O)C1CC1=CC=C(O)C=C1 XNOPRXBHLZRZKH-UHFFFAOYSA-N 0.000 abstract description 5
- 101800000989 Oxytocin Proteins 0.000 abstract description 5
- 102100031951 Oxytocin-neurophysin 1 Human genes 0.000 abstract description 5
- XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 abstract description 5
- 229960001723 oxytocin Drugs 0.000 abstract description 5
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- 210000001215 vagina Anatomy 0.000 abstract description 2
- 230000008602 contraction Effects 0.000 description 9
- 229940079593 drug Drugs 0.000 description 7
- 230000001186 cumulative effect Effects 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 5
- 210000004291 uterus Anatomy 0.000 description 5
- 241000700159 Rattus Species 0.000 description 4
- 238000005520 cutting process Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- -1 nitroglycerin) Chemical class 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 2
- 206010049816 Muscle tightness Diseases 0.000 description 2
- 230000006838 adverse reaction Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 210000000754 myometrium Anatomy 0.000 description 2
- 239000000050 smooth muscle relaxant Substances 0.000 description 2
- 230000013948 uterine smooth muscle contraction Effects 0.000 description 2
- IOVGROKTTNBUGK-SJKOYZFVSA-N (1S,2R)-ritodrine Chemical compound N([C@H](C)[C@@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJKOYZFVSA-N 0.000 description 1
- MOQVHOPVBREXLY-UHFFFAOYSA-N 3h-dioxol-4-ylmethanol Chemical compound OCC1=COOC1 MOQVHOPVBREXLY-UHFFFAOYSA-N 0.000 description 1
- UYIFTLBWAOGQBI-BZDYCCQFSA-N Benzhormovarine Chemical compound C([C@@H]1[C@@H](C2=CC=3)CC[C@]4([C@H]1CC[C@@H]4O)C)CC2=CC=3OC(=O)C1=CC=CC=C1 UYIFTLBWAOGQBI-BZDYCCQFSA-N 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical class O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 1
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
- 239000000006 Nitroglycerin Substances 0.000 description 1
- 208000005107 Premature Birth Diseases 0.000 description 1
- 206010036590 Premature baby Diseases 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- 206010046809 Uterine pain Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000012069 chiral reagent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 229950002007 estradiol benzoate Drugs 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229960003711 glyceryl trinitrate Drugs 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 229960001597 nifedipine Drugs 0.000 description 1
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
- 239000002840 nitric oxide donor Substances 0.000 description 1
- 150000002926 oxygen Chemical class 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 229960000720 ritodrine hydrochloride Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Preparation (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Inorganic Chemistry (AREA)
Abstract
本发明属于药物化学领域,提供了一种用于治疗子宫高频率平滑肌强直性收缩疾病的化合物
Description
技术领域
本发明属于药物化学领域,具体涉及一种用于诱导子宫平滑肌收缩的化合物及其药物制剂。
背景技术
子宫平滑肌过度收缩可引起青春期少女、未婚及已婚未育妇女痛经,孕期妇女早产等现象,是妇女常见病,严重影响妇女健康和工作效率。目前,临床上常用的子宫平滑肌松弛药主要有环氧化酶抑制剂(如吲哚美辛)、一氧化氮供体(如硝酸甘油)、β2受体激动剂(如盐酸利托君)及钙离子通道阻滞剂(如硝苯地平)等,这些药物可不同程度的缓解子宫疼痛症状,但具有明显的消化道、心脏、肝脏、肾脏等不良反应,疗效不持久且不宜长期服用,临床使用时具有明显的局限性。
因此,开发具有疗效确切、不良反应小的新型子宫平滑肌舒张药十分必要。
发明内容
一些实施方案中,所述R任选为F、Cl或Br;优选为Cl。
另一方面,本发明提供了一种式G化合物或其药学上可接受的盐,用于预防和/或治疗子宫平滑肌高频率强直性收缩引起的疾病或疾病状态。
另一方面,本发明提供了一种式G-01化合物或其药学上可接受的盐,用于预防和/或治疗子宫平滑肌高频率强直性收缩引起的疾病或疾病状态。
另一方面,本发明提供了一种式G化合物或其药学上可接受的盐在制备用于预防或治疗子宫平滑肌高频率强直性收缩引起的疾病或疾病状态的药物中的用途。
另一方面,本发明提供了一种式G-01化合物或其药学上可接受的盐在制备用于预防或治疗子宫平滑肌高频率强直性收缩引起的疾病或疾病状态的药物中的用途。
另一方面,本发明提供了一种栓剂,所述栓剂由Pluronic F-108、Pluronic L31、甘油和化合物G组成。
在一些优选的实施方案中,所述栓剂含由100份Pluronic F-108、1-3份PluronicL31、5 份甘油和1份化合物G组成。
在一些优选的实施方案中,所述栓剂含由100份Pluronic F-108、1份PluronicL31、5份甘油和1份化合物G组成。
在一些优选的实施方案中,所述化合物G优选为化合物G-01。
另一方面,本发明提供了一种栓剂,在制备用于预防或治疗高频率子宫平滑肌强直性收缩引起的疾病或疾病状态的药物中的用途,其中所述栓剂由Pluronic F-108、Pluronic L31、甘油和化合物G组成。
在一些优选的实施方案中,所述栓剂的制备方法如下:取100份Pluronic F-108熔融,另称取1份化合物G-01溶于5份甘油中,倒入熔融的Pluronic F-108中,趁热加入1-3份Pluronic L31,搅拌2h,脱泡,并倒入预先涂以液体石蜡的栓模中。置于4℃固化1h,取出,削去多余部分,吸去表面润滑油,包装即得。
本法所述的化合物对缩宫素引起的子宫平滑肌强直性收缩频率、幅度和活力均有显著的抑制作用,且制备得到的栓剂能够明显增强药物释放,具有显著的长效缓释效果,能够减少给药次数,增加患者的顺应性。同时栓剂可阴道给药,降低患者的副作用。
附图说明
图1为实施例3、实施例4和实施例5的累计释放曲线图。
具体实施方式
相关定义
除非有特定说明,下列用在说明书和权利要求书中的术语具有下述含义:
本发明所述的“化合物”包括所有的立体异构体和互变异构体。
本发明化合物可以是不对称的,例如,具有一个或多个立体异构体。除非另有说明,所有立体异构体都包括,如对映异构体和非对映异构体。本发明的含有不对称碳原子的化合物可以以光学活性纯的形式或外消旋形式被分离出来。光学活性纯的形式可以从外消旋混合物拆分,或通过使用手性原料或手性试剂合成。外消旋体、非对映异构体、对映异构体都包括在本发明的范围之内。
术语“任选”是指随后描述的事件或情况可能发生或可能不发生,该描述包括发生所述事件或情况和不发生所述事件或情况。
实施例1
按照专利申请CN1195353A实施例1的制备方案,将亚硝酸异戊酯加入到含[3aR-(3aα, 4α,6α,6aα)]-6-[5-氨基-6-氯-2-(丙硫基)-4-嘧啶基氨基]-四氢-2,2-二甲基-4H-环戊基-1,3-二噁环戊烯-4-甲醇的乙腈溶液中,70℃加热1h。冷却后将反应混合物浓缩纯化(SiO2,洗脱剂,二氯甲烷:乙酸乙酯,4:1)得到式G-01化合物。
实施例2
按照文献方法,制备大鼠离体子宫平滑肌条,取未孕雌性大鼠,实验前5天每天注射 2mg/kg的苯甲酸雌二醇造模。5天后,处死大鼠迅速剖取子宫,两个子宫角各取2里面长的子宫段,分别沿肌肉纹理纵向剖开,得2厘米长的子宫肌条4段,将其悬挂置于De-Jalon液中,子宫平滑肌条一段固定在浴槽内T形钩上,一段与肌肉张力换能器连接,加药前负荷1.0g,恒温37℃、饱和氧气孵育。肌肉张力换能器通过Med lab生物信号采集处理系统记录肌肉的收缩情况。
子宫平滑肌条在De-Jalon液中平衡15min,描记正常子宫平滑肌收缩活动的运动波形曲线,然后按下表加入不同的药物处理,记录子宫收缩频率和收缩幅度,计算子宫活力,即子宫活力=收缩频率×收缩幅度,每组实验平行6次。实验结果见下表。
实验结果显示,与空白对照组相比,缩宫素可显著增强大鼠子宫平滑肌运动波形,对子宫平滑肌收缩的频率、幅度和子宫活力具有显著的激动作用(P<0.01);不同浓度的化合物 G-01均对缩宫素诱导的子宫平滑肌收缩具有抑制作用(P<0.01),且随着化合物G-01浓度的升高,对缩宫素诱导的子宫平滑肌收缩的抑制作用越强。
实施例3
取1000g Pluronic F-108熔融,另称取10g化合物G-01溶于50g甘油中,倒入熔融的 Pluronic F-108中,趁热加入10gL31,磁力搅拌2h,脱泡,并倒入预先涂以液体石蜡的栓模中。置于4℃固化1h,取出,削去多余部分,吸去表面润滑油,包装即得。平均栓重1g,每枚栓剂含化合物G-01为10mg。(体外黏附时间为164.62s,24h药物累积释放率约为86.2%)
实施例4
取1010g Pluronic F-108熔融,另称取10g化合物G-01溶于50g甘油中,倒入熔融的 Pluronic F-108中,磁力搅拌2h,脱泡,并倒入预先涂以液体石蜡的栓模中。置于4℃固化1h,取出,削去多余部分,吸去表面润滑油,包装即得。平均栓重1g,每枚栓剂含化合物G-01 为10mg。(体外黏附时间为87.83s,24h药物累积释放率约为45.1%)
实施例5
称取聚氧乙烯单硬脂酸酯10g,加入PEG 400 1000g于水浴中加热,使熔融,加入化合物 G-01 10g充分搅拌至药物至溶解至匀,脱泡,将其倒入预先涂以液体石蜡的酸模型中。置于 4℃固化1h,取出,削去多余部分,吸去表面润滑油,包装即得。平均栓重1g,每枚栓剂含化合物G-01为10mg。(体外黏附时间为29.21s,24h药物累积释放率约为26.3%)
实施例6
取1000g Pluronic F-108熔融,另称取10g化合物G-01溶于50g甘油中,倒入熔融的Pluronic F-108中,趁热加入20gL31,磁力搅拌2h,脱泡,并倒入预先涂以液体石蜡的栓模中。置于4℃固化1h,取出,削去多余部分,吸去表面润滑油,包装即得。平均栓重1g,每枚栓剂含化合物G-01为10mg。(体外黏附时间为153.19s,24h药物累积释放率约为84.9%)
实施例7
Claims (6)
2.如权利要求1所述的栓剂,其中所述化合物G中,R任选为F、Cl或Br。
4.如权利要求1所述的栓剂,由100份Pluronic F-108、1份Pluronic L31、5份甘油和1份化合物G组成。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110099693.4A CN112915063B (zh) | 2021-01-25 | 2021-01-25 | 一种用于治疗子宫平滑肌高频率强直性收缩相关疾病的化合物 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110099693.4A CN112915063B (zh) | 2021-01-25 | 2021-01-25 | 一种用于治疗子宫平滑肌高频率强直性收缩相关疾病的化合物 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN112915063A CN112915063A (zh) | 2021-06-08 |
CN112915063B true CN112915063B (zh) | 2022-12-20 |
Family
ID=76167639
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202110099693.4A Active CN112915063B (zh) | 2021-01-25 | 2021-01-25 | 一种用于治疗子宫平滑肌高频率强直性收缩相关疾病的化合物 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN112915063B (zh) |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE69621021T2 (de) * | 1995-07-11 | 2002-10-31 | Astrazeneca Ab | Inhibitoren der plättchenaggregation |
US6197327B1 (en) * | 1997-06-11 | 2001-03-06 | Umd, Inc. | Device and method for treatment of dysmenorrhea |
SE9904129D0 (sv) * | 1999-11-15 | 1999-11-15 | Astra Pharma Prod | Novel compounds |
CN102924457A (zh) * | 2011-08-12 | 2013-02-13 | 上海恒瑞医药有限公司 | 三唑并嘧啶类衍生物、其制备方法及其用途 |
-
2021
- 2021-01-25 CN CN202110099693.4A patent/CN112915063B/zh active Active
Also Published As
Publication number | Publication date |
---|---|
CN112915063A (zh) | 2021-06-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN101516840B (zh) | 取代的n-酰基苯胺及其应用方法 | |
KR101986272B1 (ko) | 삼환식 화합물, 이를 포함하는 조성물 및 그의 용도 | |
SU988190A3 (ru) | Способ получени гидантоина | |
JP2000511203A (ja) | ピラジン化合物 | |
JP2001525322A (ja) | 胃酸分泌を抑制する複素環式化合物、それらの製造法およびそれらの医薬組成物 | |
JP2021532108A (ja) | ビス第四級アンモニウム化合物及びその製造方法と使用 | |
EP1202729A1 (en) | Phosphate transport inhibitors | |
KR20190025989A (ko) | sGC 자극제의 고체 형태 | |
EP3458448A1 (en) | Methods of using fasn inhibitors | |
JP2020518676A (ja) | トランス−[テトラクロロビス(1h−インダゾール)ルテニウム酸(iii)]及びその組成物の製造 | |
CN112915063B (zh) | 一种用于治疗子宫平滑肌高频率强直性收缩相关疾病的化合物 | |
WO2001087294A1 (en) | Phosphate transport inhibitors | |
CN112876485A (zh) | 一种用于治疗子宫平滑肌高频率强直性收缩相关疾病的化合物 | |
EP2767533B1 (en) | Derivative of butylphthalide and preparation method and use thereof | |
JP2019531353A (ja) | 重水素化化合物及びその医薬的用途 | |
JPH05213755A (ja) | 肝臓障害治療薬 | |
CN103193792A (zh) | 一种治疗缺血性心脑血管疾病的新化合物 | |
JP2014503501A (ja) | 治療的有用性を伴う受容体調節因子としての新規化合物 | |
JP2017513934A (ja) | フェナントロリンホスホン酸誘導体及びその調製方法と応用 | |
CA2690945A1 (en) | Transdermal or transmucosal pharmaceutical composition comprising 1-(benzofuran-2-yl)-2-propylaminopentane | |
KR100816798B1 (ko) | 의약용 트리에틸렌테트라민 이염산염의 제조방법 | |
JP2022531570A (ja) | ジアミノピリミジン化合物を使用することによって、子宮内膜症性疼痛を治療する方法 | |
US10183908B2 (en) | Compositions for the treatment of kidney and/or liver disease | |
CN112500413B (zh) | 一类黄嘌呤芳酸醚衍生物,其制备方法及用途 | |
US20220387364A1 (en) | Methods to decrease triglyceride synthesis in the liver |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20221130 Address after: 238014 Room 904, Unit 2, Building 20, Phoenix City, Dongfeng Neighborhood Committee, Chaohu City, Anhui Province Applicant after: Liu Hongmei Address before: No.353, East Changjiang Road, Huangdao District, Qingdao City, Shandong Province 266555 Applicant before: Guo Liwei |
|
TA01 | Transfer of patent application right | ||
GR01 | Patent grant | ||
GR01 | Patent grant |