CN110548034A - 一种怀孕阻断药物 - Google Patents
一种怀孕阻断药物 Download PDFInfo
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- CN110548034A CN110548034A CN201910630763.7A CN201910630763A CN110548034A CN 110548034 A CN110548034 A CN 110548034A CN 201910630763 A CN201910630763 A CN 201910630763A CN 110548034 A CN110548034 A CN 110548034A
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- norethindrone
- norethindrone acetate
- drospirenone
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- 239000003814 drug Substances 0.000 title claims abstract description 26
- IMONTRJLAWHYGT-ZCPXKWAGSA-N Norethindrone Acetate Chemical compound C1CC2=CC(=O)CC[C@@H]2[C@@H]2[C@@H]1[C@@H]1CC[C@](C#C)(OC(=O)C)[C@@]1(C)CC2 IMONTRJLAWHYGT-ZCPXKWAGSA-N 0.000 claims abstract description 42
- 229960001652 norethindrone acetate Drugs 0.000 claims abstract description 42
- METQSPRSQINEEU-UHFFFAOYSA-N dihydrospirorenone Natural products CC12CCC(C3(CCC(=O)C=C3C3CC33)C)C3C1C1CC1C21CCC(=O)O1 METQSPRSQINEEU-UHFFFAOYSA-N 0.000 claims abstract description 27
- 229960004845 drospirenone Drugs 0.000 claims abstract description 27
- METQSPRSQINEEU-HXCATZOESA-N drospirenone Chemical compound C([C@]12[C@H]3C[C@H]3[C@H]3[C@H]4[C@@H]([C@]5(CCC(=O)C=C5[C@@H]5C[C@@H]54)C)CC[C@@]31C)CC(=O)O2 METQSPRSQINEEU-HXCATZOESA-N 0.000 claims abstract description 27
- 229960003843 cyproterone Drugs 0.000 claims abstract description 18
- DUSHUSLJJMDGTE-ZJPMUUANSA-N cyproterone Chemical compound C1=C(Cl)C2=CC(=O)[C@@H]3C[C@@H]3[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)C)(O)[C@@]1(C)CC2 DUSHUSLJJMDGTE-ZJPMUUANSA-N 0.000 claims abstract description 18
- IMSSROKUHAOUJS-MJCUULBUSA-N mestranol Chemical compound C1C[C@]2(C)[C@@](C#C)(O)CC[C@H]2[C@@H]2CCC3=CC(OC)=CC=C3[C@H]21 IMSSROKUHAOUJS-MJCUULBUSA-N 0.000 claims abstract description 17
- 229960001390 mestranol Drugs 0.000 claims abstract description 17
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- VKHAHZOOUSRJNA-GCNJZUOMSA-N mifepristone Chemical compound C1([C@@H]2C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]3CC[C@@]([C@]3(C2)C)(O)C#CC)=CC=C(N(C)C)C=C1 VKHAHZOOUSRJNA-GCNJZUOMSA-N 0.000 claims abstract description 17
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- 238000006243 chemical reaction Methods 0.000 claims abstract description 8
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 claims abstract description 5
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- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 21
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Classifications
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/567—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in position 17 alpha, e.g. mestranol, norethandrolone
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
- A61K31/585—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin containing lactone rings, e.g. oxandrolone, bufalin
-
- 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
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/18—Feminine contraceptives
Abstract
本发明属于医药技术领域,提供一种怀孕阻断药物,单次计量单元包括如下组分:0.2mg‑0.5mg炔诺酮醋酸脂、10μg‑50μg孕二烯酮、0.1mg‑2mg屈螺酮、3μg‑20μg美雌醇和40g‑60g一水乳糖;通过炔诺酮醋酸脂、环丙孕酮、米非司酮与屈螺酮产生化学反应,达到怀孕阻断功效,同时通过炔雌醇刺激促性腺激素分泌,从而抑制卵巢的排卵,达到抗生育作用,通过美雌醇治疗暖巢功能不全、闭经、功能性子宫出血和跟年期综合症等症状,以解决目前市场上的怀孕阻断药物,副作用力大,使用者容易产生月经不调、子宫功能性出血和子宫内膜异位症等病状的问题。
Description
技术领域
本发明属于医药技术领域,具体涉及一种怀孕阻断药物。
背景技术
计划生育是我国的一项基本国策,保证公民知情选择安全、有效、适宜的避孕节育措施,加强免费避孕药具的管理、发放、使用和服务,是落实计划生育政策的有力保障。
目前市场上的怀孕阻断药物,副作用力大,使用者容易产生月经不调、子宫功能性出血和子宫内膜异位症等病状。
发明内容
本发明在于提供一种怀孕阻断药物,以解决目前市场上的怀孕阻断药物,副作用力大,使用者容易产生月经不调、子宫功能性出血和子宫内膜异位症等病状的问题。
本发明是这样实现的,本发明提供一种怀孕阻断药物,单次计量单元包括如下组分:0.2mg-0.5mg炔诺酮醋酸脂、10μg-50μg孕二烯酮、0.1mg-2mg屈螺酮、3μg-20μg美雌醇和40g-60g一水乳糖。
优选的,还包括6μg-15μg炔雌醇,其中,所述炔雌醇和所述美雌醇的含量之和不超过25μg。
优选的,还包括3mg-8mg环丙孕酮,其中,所述环丙孕酮、孕二烯酮、炔诺酮醋酸脂和屈螺酮的含量之和在3.2mg-15mg之间。
优选的,还包括0.1mg-1mg米非司酮,其中,所述米非司铜和炔诺酮醋酸脂的含量之和不超过1.5mg。
优选的,还包括1.5mg-3.5mg地屈孕酮,其中,所述地屈孕酮的用量小于所述炔诺酮醋酸脂、屈螺酮和米非司酮的用量之和。
优选的,所述炔诺酮醋酸脂的制备材料为炔诺酮。
优选的,所述炔诺酮醋酸脂的制备过程包括如下步骤:
步骤A:将1.0g炔诺酮放置于50ml圆底烧杯中,加入10ml醋酐和10ml二甲苯,搅拌并加热至160摄氏度使之回流,并用3A分子筛脱水,反应6小时,
步骤B:向50ml圆底烧杯加入0.5g醋酸钠,通水汽蒸馏去除二甲苯,并将残留物冷至室温,过滤得1.1g淡黄色固体,
步骤C:加入10ml甲醇并用10%碳酸钾水溶液将淡黄色固体PH 值调至7-8,室温搅拌2小时,对反应过程中生成的炔诺酮双酯进行水解,加20ml水过滤,通过乙酸乙酯重结晶制得炔诺酮醋酸脂。
与现有的方法相比,本发明的有益效果是:通过炔诺酮醋酸脂、环丙孕酮、米非司酮与屈螺酮产生化学反应,达到怀孕阻断功效,同时通过炔雌醇刺激促性腺激素分泌,从而抑制卵巢的排卵,达到抗生育作用,同时通过美雌醇治疗暖巢功能不全、闭经、功能性子宫出血和跟年期综合症等症状,以解决目前市场上的怀孕阻断药物,副作用力大,使用者容易产生月经不调、子宫功能性出血和子宫内膜异位症等病状的问题。
具体实施方式
下面将结合发明实施例对发明实施例中的技术方法进行清楚、完整地描述,显然,所描述的实施例仅仅是发明一部分实施例,而不是全部的实施例。基于发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于发明保护的范围。
实施例1
本发明提供一种怀孕阻断药物,单次计量单元包括如下组分: 0.2mg-0.5mg炔诺酮醋酸脂、10μg-50μg孕二烯酮、0.1mg-2mg屈螺酮、3μg-20μg美雌醇和40g-60g一水乳糖。
在本实施方式中,炔诺酮醋酸酯是一种孕激素,常用于月经不调、子宫功能性出血、子宫内膜异位症等病状,屈螺酮抑制排卵和改变宫颈粘液,同时屈螺酮可以调节月经周期,使女性月经周期规律,痛经减少和出血量少,屈螺酮具有扛盐皮质激素活性,能防止由于体液潴留而引起的体重增加和其他症状,屈螺酮对抗与雌激素相关的钠潴留,提供良好的耐受性,并对经前期综合征有积极作用,与炔雌醇组成复方,屈螺酮增高了高密酯蛋白水平,显示良好的脂质谱,屈螺酮的抗雄激素活性对皮肤有良好的作用,减少痤疮损伤及皮酯的产生,美雌醇临床用于暖巢功能不全、闭经、功能性子宫出血和更年期综合症等,一水乳糖是片剂和胶囊制剂生产中所需的重要物质,是医药、营养和治疗片剂中较常选用的糖类,能溶于水,无刺激性气味,在空气中具有高度稳定性,可长期储存,易于操作掌握,且与大多数活性药物成分不起作用。
进一步的,还包括6μg-15μg炔雌醇,其中,所述炔雌醇和所述美雌醇的含量之和不超过25μg。
在本实施方式中,炔雌醇对下丘脑和垂体有正、负反馈作用,小计量可刺激促性腺激素分泌,大剂量则抑制其分泌,从而抑制卵巢的排卵,达到抗生育作用,绝雌醇能刺激垂体合成和释放促性腺激素,促性腺激素则刺激性腺释放性激素,下丘脑分泌促性腺激素释放素受多种因素的调控,其中包括循环中的性激素,其中包括循环中的性激素,单剂量使用时能增加循环中的性激素;连续使用可致腺垂体中促性腺激素释放素受体下调,从而减少性激素的分泌,通过设置炔雌醇和所述美雌醇的含量之和不超过15μg降低炔雌醇连续使用时可致腺垂体中促性腺激素释放素受体下调,从而减少性激素的分泌的副作用。
进一步的,还包括3mg-8mg环丙孕酮,其中,所述环丙孕酮、孕二烯酮、炔诺酮醋酸脂和屈螺酮的含量之和在3.2mg-15mg之间。
在本实施方式中,环丙孕酮为17-羟孕酮类衍生物,具有很强的抗雄性激素作用,能抑制垂体促性腺的分泌,使体内睾酮水平降低,减少精子数及其活动度,降低精子生化组成及精子穿透宫颈黏液的能力,同时对有避孕要求的女性痤疮患者可作为第一线药物,通过设置环丙孕酮、孕二烯酮、炔诺酮醋酸脂和屈螺酮的含量之和在 3.2mg-15mg之间减少环丙孕酮的大量使用,环丙孕酮大量使用容易出现肝功能受损、气喘等不良影响
进一步的,还包括0.1mg-1mg米非司酮,其中,所述米非司铜和炔诺酮醋酸脂的含量之和不超过1.5mg。
在本实施方式中,米菲司酮为新型抗孕激素,并无孕激素、雌激素、雄激素及抗雌激素活性,能与孕酮受体及糖皮质激素受体结合,对子宫内膜孕酮受体的亲和力比黄体酮强五倍,对受孕动物各期妊娠均有引产效应,可作为非手术性抗早孕药,在有效剂量下对皮质醇水平无明显影响,由于米非司酮不能引发足够的子宫活性,单用与抗早孕时不完全流产率高,能增强子宫对前列腺的敏感性,故在产品中通过设置米非司铜和炔诺酮醋酸脂的含量之和不超过1.5mg可达到抗早孕、催经止孕等避孕效果。
进一步的,还包括1.5mg-3.5mg地屈孕酮,其中,所述地屈孕酮的用量小于所述炔诺酮醋酸脂、屈螺酮和米非司酮的用量之和。
在本实施方式中,地屈孕酮是一种口服孕激素,可使子宫内膜进入完全的分泌相,从而可防止雄性激素引起的子宫内膜增生和癌变风险,地屈孕酮可用于内源性孕激素不足的各种疾病,地屈孕酮无雌激素,雄激素及肾上腺皮质激素作用,地屈孕酮不产热,且对脂代谢无影响,通过设置地屈孕酮的用量小于所述炔诺酮醋酸脂、屈螺酮和米非司酮的用量之和,炔诺酮醋酸脂、屈螺酮和米非司酮对人体产生避孕功效时,调节人体由于内源性孕激素不足产生的各种病状。
进一步的,所述炔诺酮醋酸脂的制备材料为炔诺酮。
在本实施方式中,炔诺酮醋酸脂在临床上主要作为女用口服避孕药,炔诺酮酸脂的合成以炔诺酮为原料,在吡啶存在下,用醋酐酰化或以对甲苯磺酸为催化剂,用醋酐酰化生成,炔诺酮醋酸酯在产出时容易出现少量炔酮酸脂影响炔诺酮醋酸酯纯度。
进一步的,所述炔诺酮醋酸脂的制备过程包括如下步骤:
步骤A:将1.0g炔诺酮放置于50ml圆底烧杯中,加入10ml醋酐和10ml二甲苯,搅拌并加热至160摄氏度使之回流,并用3A分子筛脱水,反应6小时,
步骤B:向50ml圆底烧杯加入0.5g醋酸钠,通水汽蒸馏去除二甲苯,并将残留物冷至室温,过滤得1.1g淡黄色固体,
步骤C:加入10ml甲醇并用10%碳酸钾水溶液将淡黄色固体PH 值调至7-8,室温搅拌2小时,对反应过程中生成的炔诺酮双酯进行水解,加20ml水过滤,通过乙酸乙酯重结晶制得炔诺酮醋酸脂。
在本实施方式中,将1.0g炔诺酮放置于50ml圆底烧杯中,加入 10醋酐和10ml二甲笨,搅拌加热至160摄氏度使之回流,并用3A 分子筛脱水,反应6小时后,向50ml圆底烧杯中加入0.5g醋酸钠,通水汽蒸馏祛除二甲苯,并将残留物冷至室温,过滤得1.1g淡黄色固体,加入10ml甲醇并用10%碳酸钾水溶液将淡黄色固体的PH值调至7-8,室温搅拌2小时,对反应过程中生成的炔诺酮双酯进行水解,加20ml水过滤,通过乙酸乙酯重结晶制得高纯度炔诺酮醋酸酯,通过在原有的的水汽蒸馏操作中加入醋酸钠,使之与醋酐水解生成的醋酸形成缓冲对,从而使整个体系的酸度变弱,抑制炔诺酮醋酸酯的水解,提高炔诺酮醋酸酯纯度。
实施例2
如上述实施例1所述,在本实施例中,
进一步的,所述单次计量单元包括如下组分:0.2mg炔诺酮醋酸酯、10μg孕二烯酮、0.1mg屈螺酮、3μg美雌酮、6μg炔雌酮、3mg 环丙孕酮、0.1mg米非司酮和1.5mg地屈孕酮。
在本实施方式中,3μg美雌酮和6μg炔雌酮含量之和不超过25 μg,通过设置3μg美雌酮降低炔雌醇连续使用时可致腺垂体中促性腺激素释放素受体下调,从而减少性激素的分泌的副作用,同时3μ g美雌醇临床用于暖巢功能不全、闭经、功能性子宫出血和更年期综合症等病状,通过设置3mg环丙孕酮、10μg孕二烯酮、0.2mg炔诺酮醋酸脂和0.1mg屈螺酮的含量之和在3.2mg-15mg之间,3mg环丙孕酮、10μg孕二烯酮、0.2mg炔诺酮醋酸脂和0.1mg屈螺酮产生反应进行怀孕阻断。
实施例3
如上述实施例1所述,在本实施例中,
进一步的,所述单次计量单元包括如下组分:0.5mg炔诺酮醋酸酯、50μg孕二烯酮、2mg屈螺酮、10μg美雌酮、15μg炔雌酮、8mg 环丙孕酮、1mg米非司酮和1.4mg地屈孕酮。
在本实施方式中,10μg美雌酮和15μg炔雌酮含量之和不超过 25μg,通过设置10μg美雌酮降低炔雌醇连续使用时可致腺垂体中促性腺激素释放素受体下调,从而减少性激素的分泌的副作用,15 μg炔雌酮含量的大剂量使用抑制促性腺激素分泌,从而抑制卵巢的排卵,达到抗生育作用,同时10μg美雌醇临床用于暖巢功能不全、闭经、功能性子宫出血和更年期综合症等病状,通过设置8mg环丙孕酮、50μg孕二烯酮、0.5mg炔诺酮醋酸脂和2mg屈螺酮的含量之和在3.2mg-15mg之间,8mg环丙孕酮、50μg孕二烯酮、0.5mg炔诺酮醋酸脂和2mg屈螺酮产生反应进行怀孕阻断。
可以理解在不脱离发明的原理和精神的情况下可以对这些实施例进行多种变化、修改、替换和变型,发明的范围由所附权利要求及其等同物限定。
Claims (7)
1.一种怀孕阻断药物,其特征在于:单次计量单元包括如下组分:0.2mg-0.5mg炔诺酮醋酸脂、10μg-50μg孕二烯酮、0.1mg-2mg屈螺酮、3μg-20μg美雌醇和40g-60g一水乳糖。
2.根据权利要求1所述的一种怀孕阻断药物,其特征在于:还包括6μg-15μg炔雌醇,其中,所述炔雌醇和所述美雌醇的含量之和不超过25μg。
3.根据权利要求1所述的一种怀孕阻断药物,其特征在于:还包括3mg-8mg环丙孕酮,其中,所述环丙孕酮、孕二烯酮、炔诺酮醋酸脂和屈螺酮的含量之和在3.2mg-15mg之间。
4.根据权利要求1所述的一种怀孕阻断药物,其特征在于:还包括0.1mg-1mg米非司酮,其中,所述米非司铜和炔诺酮醋酸脂的含量之和不超过1.5mg。
5.根据权利要求4所述的一种怀孕阻断药物,其特征在于:还包括1.5mg-3.5mg地屈孕酮,其中,所述地屈孕酮的用量小于所述炔诺酮醋酸脂、屈螺酮和米非司酮的用量之和。
6.根据权利要求1所述的一种怀孕阻断药物,其特征在于:所述炔诺酮醋酸脂的制备材料为炔诺酮。
7.根据权利要求6所述的一种怀孕阻断药物,其特征在于:所述炔诺酮醋酸脂的制备过程包括如下步骤:
步骤A:将1.0g炔诺酮放置于50ml圆底烧杯中,加入10ml醋酐和10ml二甲苯,搅拌并加热至160摄氏度使之回流,并用3A分子筛脱水,反应6小时,
步骤B:向50ml圆底烧杯加入0.5g醋酸钠,通水汽蒸馏去除二甲苯,并将残留物冷至室温,过滤得1.1g淡黄色固体,
步骤C:加入10ml甲醇并用10%碳酸钾水溶液将淡黄色固体PH值调至7-8,室温搅拌2小时,对反应过程中生成的炔诺酮双酯进行水解,加20ml水过滤,通过乙酸乙酯重结晶制得炔诺酮醋酸脂。
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Application publication date: 20191210 |
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