CN106580914A - 一种盐酸维拉佐酮软胶囊及其制备方法 - Google Patents
一种盐酸维拉佐酮软胶囊及其制备方法 Download PDFInfo
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- CN106580914A CN106580914A CN201710109065.3A CN201710109065A CN106580914A CN 106580914 A CN106580914 A CN 106580914A CN 201710109065 A CN201710109065 A CN 201710109065A CN 106580914 A CN106580914 A CN 106580914A
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- vilazodone hydrochloride
- soft capsule
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- softgel shell
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- RPZBRGFNBNQSOP-UHFFFAOYSA-N vilazodone hydrochloride Chemical compound Cl.C1=C(C#N)C=C2C(CCCCN3CCN(CC3)C=3C=C4C=C(OC4=CC=3)C(=O)N)=CNC2=C1 RPZBRGFNBNQSOP-UHFFFAOYSA-N 0.000 title claims abstract description 58
- 229960003381 vilazodone hydrochloride Drugs 0.000 title claims abstract description 56
- 238000002360 preparation method Methods 0.000 title claims abstract description 30
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 75
- 239000007901 soft capsule Substances 0.000 claims description 42
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 36
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 28
- 229960002216 methylparaben Drugs 0.000 claims description 27
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 claims description 26
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 claims description 26
- 235000011187 glycerol Nutrition 0.000 claims description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
- 239000002775 capsule Substances 0.000 claims description 19
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- 239000000203 mixture Substances 0.000 claims description 14
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- 229960003740 vilazodone Drugs 0.000 claims description 12
- SGEGOXDYSFKCPT-UHFFFAOYSA-N vilazodone Chemical compound C1=C(C#N)C=C2C(CCCCN3CCN(CC3)C=3C=C4C=C(OC4=CC=3)C(=O)N)=CNC2=C1 SGEGOXDYSFKCPT-UHFFFAOYSA-N 0.000 claims description 12
- -1 ethyl hydroxyl Chemical group 0.000 claims description 11
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- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 11
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- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
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- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
- 239000005711 Benzoic acid Substances 0.000 claims description 2
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 claims description 2
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- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
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- RWPGFSMJFRPDDP-UHFFFAOYSA-L potassium metabisulfite Chemical compound [K+].[K+].[O-]S(=O)S([O-])(=O)=O RWPGFSMJFRPDDP-UHFFFAOYSA-L 0.000 claims description 2
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- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims description 2
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- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 claims 1
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- UDEWPOVQBGFNGE-UHFFFAOYSA-N propyl benzoate Chemical compound CCCOC(=O)C1=CC=CC=C1 UDEWPOVQBGFNGE-UHFFFAOYSA-N 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
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- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
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- SNIXRMIHFOIVBB-UHFFFAOYSA-N N-Hydroxyl-tryptamine Chemical compound C1=CC=C2C(CCNO)=CNC2=C1 SNIXRMIHFOIVBB-UHFFFAOYSA-N 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
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- YJYPHIXNFHFHND-UHFFFAOYSA-N agomelatine Chemical compound C1=CC=C(CCNC(C)=O)C2=CC(OC)=CC=C21 YJYPHIXNFHFHND-UHFFFAOYSA-N 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
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- 230000001430 anti-depressive effect Effects 0.000 description 1
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- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
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- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
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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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4816—Wall or shell material
- A61K9/4825—Proteins, e.g. gelatin
-
- 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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明涉及一种盐酸维拉佐酮软胶囊的制备方法。制备得到的依维莫司软胶囊具有稳定性好,性状稳定的优点。本发明的治疗抑郁症的药物组合,配比合理,可以快速释放药物,对所述病症能产生很好的疗效。
Description
技术领域
本发明属于药物制剂领域,涉及一种含有盐酸维拉佐酮的软胶囊及其制备方法。
背景技术
盐酸维拉佐酮由美国Trovis Pharmaceuticals LLC公司开发,是第一个吲哚烷基胺类新型治疗成人重度抑郁症的药物,具有选择性的5羟色胺再摄取抑制剂和5-HT1A受体部分激动剂双重作用。2011年1月美国食品药品管理局(FDA)批准盐酸维拉佐酮片用于治疗成年人中重度抑郁症(Major depressive disorder,MDD)的治疗,维拉唑酮的商品名为Viibryd。 盐酸维拉唑酮(vilazodone)为一种新型抗抑郁药,盐酸维拉佐酮与5-羟色胺再摄取位点高亲和力结合(Ki= 0.1 nM),但与去甲肾上腺素(Ki=56 nM)或多巴胺(Ki=37 nM)再摄取位点没有高亲和力。盐酸维拉佐酮选择性地抑制5-羟色胺再摄取(IC50= 1.6 nM)。维拉佐酮还高亲和力与5-HT1A受体结合(IC50=2.1 nM),是5-HT1A受体部分激动剂。 产品优势临床数据试验表明,盐酸维拉佐酮具有起效快,不增体重,也不影响性功能,其疗效明显优于安慰剂,耐受性好,不良反应小。其常见(发生率≥5%和至少是安慰剂率发生率的2倍)不良反应为腹泻、恶心、呕吐和失眠。这些不良反应发生在治疗早期,不会导致终止盐酸维拉唑酮的治疗。 市场预测预计Viibryd的年销售额有望突破10亿美元。新产品在全球7大市场的上市将会使抑郁症药物市场迅速扩容,预计将从2010年的119亿美元增长到2020年的140亿美元,复合年均增长率为2.5%,使抑郁症药物市场成为中枢神经系统疾病领域最大的分支。目前的在研抑郁症新药未来将会作为二线和三线治疗药物争夺抑郁症药物市场份额。根据相关治疗指南,医师处方的抑郁症药物通常是首选一种常用的ssris类药的仿制药,然后再搭配一种药物(如阿戈美拉汀,维拉佐酮或lu aa21004)作为初始治疗,所以市场前景非常值得期待。
发明内容
针对现有的盐酸维拉佐酮胶囊溶出率低的特点,本发明提供一种盐酸维拉佐酮软胶囊。
具体而言,本发明所述软胶囊包括囊壳和内容物,按重量份,其原料包括如下组分:
囊壳:明胶10份、甘油3.5-4.5份、水10份,防腐剂1.0-3.5份;
内容物:盐酸维拉佐酮1-10份、稀释剂40-90份、助悬剂1-5份、抗氧剂0-3份、防腐剂0-3份;
所述囊壳和内容物的重量比为2:5。
本发明中,所述稀释剂包括聚乙二醇类或植物油的一种或两种,其中聚乙二醇类选自聚乙二醇400、聚乙二醇2000,植物油选自玉米油、大豆油、花生油、麻油、橄榄油、葵花籽油、色拉油、棉籽油或菜籽油。所述稀释剂优选为聚乙二醇400、聚乙二醇2000。采用该稀释剂有利于保证含量准确和制剂的稳定性,从而确保药品的安全有效性。
本发明中,所述助悬剂包括乙基羟乙基纤维、甲壳糖、甲基纤维素、乙基纤维素、琼脂、羟乙基甲基纤维素、羟乙基纤维素、羟丙基甲基纤维素、羟丙基纤维素、苯甲酸、聚乙二醇等中一种或几种,所述助悬剂优选为乙基纤维素、羟丙基甲基纤维素,采用该助悬剂有利于增加分散介质的黏度以降低微粒的沉降速度或增加微粒亲水性。
本发明中,所述抗氧剂包括亚硫酸氢钠、焦亚硫酸钠、焦亚硫酸钾、乙二胺四乙酸、枸橼酸、苹果酸、抗坏血酸、肌醇等中的一种或几种,优选为抗坏血酸、乙二胺四乙酸,采用该抗氧化剂有利于防止药物氧化变质、囊壁老化导致药物崩解延长等问题,还可以起到金属离子螯合剂的作用。
本发明中,所述防腐剂包括山梨酸、对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯等中一种或几种,所述防腐剂优选对羟基苯甲酸甲酯、山梨酸。这两种防腐剂是广谱型防腐剂,具有性质稳定毒性低的特点。
本发明中,内容物中还可添加潜溶剂,所述潜溶剂选自乙醇、甘油或丙二醇。
进一步,本发明优选所述软胶囊,按重量份,原料包括如下组分:
囊壳:明胶10份、甘油3.5-4.5份、水10份,对羟基苯甲酸甲酯1.0-3.5份;
内容物:盐酸维拉佐酮1-10份,稀释剂聚乙二醇400,50-60份,助悬剂甲壳糖1-4份、羟丙基甲基纤维素1-4份,抗氧剂抗坏血酸1-2份,防腐剂对羟基苯甲酸甲酯1-2份;
所述囊壳和内容物的重量比为2:5。
本发明同时提供了上述盐酸维拉佐酮软胶囊的制备方法,所述制备方法包括如下步骤:
1)囊壳液的制备:将明胶、甘油和水按比例混合均匀,80-90℃水浴加热溶解,加入适量防腐剂,搅拌,抽真空脱气后,50-70℃保温备用;
2)内容物的制备:将该固体分散体与稀释剂、助悬剂、抗氧剂、防腐剂充分混合均匀;
3)将内容物与囊壳液制成软胶囊。所述所述步骤2)中还可加入潜溶剂。
具体实施方式
以下实施例用于说明本发明,但不用来限制本发明的范围。
实施例1盐酸维拉佐酮软胶囊
囊壳:明胶1.25g、甘油0.45g、水.12g、对羟基苯甲酸甲酯0.15g。
内容物: 盐酸维拉佐酮20mg、聚乙二醇400 3g、甲壳糖0.25g、羟丙基甲基纤维素0.13g、抗坏血酸0.1g、对羟基苯甲酸甲酯0.05g。
实施例2 盐酸维拉佐酮软胶囊
囊壳:明胶1.35g,甘油0.50g,水1.21g,对羟基苯甲酸甲酯0.23g。
内容物:称取盐酸维拉佐酮20mg、聚乙二醇400 4g、甘油0.25g、羟丙基甲基纤维素0.1g、抗坏血酸0.12g、对羟基苯甲酸甲酯0.03g。
实施例3 盐酸维拉佐酮软胶囊
囊壳:明胶1.45g,甘油0.60g,水1.3g,对羟基苯甲酸甲酯0.15g。
内容物:称取盐酸维拉佐酮40mg、聚乙二醇400 4.3g、甲壳糖0.2g、羟丙基甲基纤维素0.1g、抗坏血酸0.10g、对羟基苯甲酸甲酯0.02g。
实施例4盐酸维拉佐酮软胶囊
囊壳:明胶1.26g、甘油0.58g、水1.13g、对羟基苯甲酸甲酯0.45g。
内容物:称取盐酸维拉佐酮50mg、聚乙二醇2000 4g、乙基纤维素0.22g、羟丙基甲基纤维素0.1g、抗坏血酸0.13g、对羟基苯甲酸甲酯0.04g。
实施例5盐酸维拉佐酮软胶囊
囊壳:明胶1.22g、甘油0.51g、水1.1g、对羟基苯甲酸甲酯0.4g。
内容物:称取盐酸维拉佐酮50mg、聚乙二醇2000 6g、乙基纤维素0.5g、羟丙基甲基纤维素0.1g。
实施例6盐酸维拉佐酮软胶囊
囊壳:明胶1.2g、甘油0.55g、水1.1g、对羟基苯甲酸甲酯0.42g。
内容物:称取盐酸维拉佐酮100mg、聚乙二醇2000 3g、乙基纤维素0.21g、羟丙基甲基纤维素0.2g、抗坏血酸0.2g、对羟基苯甲酸甲酯0.2g。
实施例7盐酸维拉佐酮软胶囊的制备
按照实施例1处方制备盐酸维拉佐酮软胶囊,其步骤如下:
1)囊壳液的制备:将明胶、甘油和水混合均匀,80℃水浴加热溶解,加入对羟基苯甲酸甲酯,经搅拌,抽真空脱气后,70℃保温备用;
2)囊壳内容物的制备:称取盐酸维拉佐酮固体分散体、聚乙二醇400、甲壳糖、羟丙基甲基纤维素、抗坏血酸、对羟基苯甲酸甲酯混合均匀,备用;
3)将上述的囊壳内容物与囊壳液装入自动旋转轧囊机中,温度控制在40-50℃,制备成盐酸维拉佐酮软胶囊。
实施例8 盐酸维拉佐酮软胶囊的制备
按照实施例2配方制备盐酸维拉佐酮软胶囊,其步骤如下:
1)囊壳液的制备:称取明胶,甘油,水,混合均匀,80℃水浴加热溶解,加入对羟基苯甲酸甲酯经搅拌,抽真空脱气后,70℃保温备用;
2)囊壳内容物的制备:称取盐酸维拉佐酮固体分散体4g、聚乙二醇、甘油、羟丙基甲基纤维素、抗坏血酸、对羟基苯甲酸甲酯,混合均匀,备用;
3)将上述的囊壳内容物与囊壳装入自动旋转轧囊机中,温度控制在40-50℃,制备成盐酸维拉佐酮软胶囊。
实施例9盐酸维拉佐酮软胶囊的制备
按照实施例3的配方制备盐酸维拉佐酮软胶囊,其步骤如下:
1)囊壳液的制备:称取明胶,甘油,水,混合均匀,80℃水浴加热溶解,加入对羟基苯甲酸甲酯经搅拌,抽真空脱气后,70℃保温备用;
2)囊壳内容物的制备:称取盐酸维拉佐酮固体分散体4g、聚乙二醇、甘油、羟丙基甲基纤维素、抗坏血酸、对羟基苯甲酸甲酯,混合均匀,备用;
3)将上述的囊壳内容物与囊壳装入自动旋转轧囊机中,温度控制在40-50℃,制备成盐酸维拉佐酮软胶囊。
实施例10盐酸维拉佐酮软胶囊的制备
按照实施例4的配方制备盐酸维拉佐酮软胶囊,其步骤如下:
1)囊壳液的制备:称取明胶,甘油,水,混合均匀,80℃水浴加热溶解,加入对羟基苯甲酸甲酯经搅拌,抽真空脱气后,70℃保温备用;
2)囊壳内容物的制备:称取盐酸维拉佐酮固体分散体4g、聚乙二醇、甘油、羟丙基甲基纤维素、抗坏血酸、对羟基苯甲酸甲酯,混合均匀,备用;
3)将上述的囊壳内容物与囊壳装入自动旋转轧囊机中,温度控制在40-50℃,制备成盐酸维拉佐酮软胶囊。
实施例11盐酸维拉佐酮软胶囊的制备
按照实施例5的配方制备盐酸维拉佐酮软胶囊,其步骤如下:
1)囊壳液的制备:称取明胶,甘油,水,混合均匀,80℃水浴加热溶解,加入对羟基苯甲酸甲酯经搅拌,抽真空脱气后,70℃保温备用;
2)囊壳内容物的制备:称取盐酸维拉佐酮固体分散体4g、聚乙二醇、甘油、羟丙基甲基纤维素、抗坏血酸、对羟基苯甲酸甲酯,混合均匀,备用;
3)将上述的囊壳内容物与囊壳装入自动旋转轧囊机中,温度控制在40-50℃,制备成盐酸维拉佐酮软胶囊。
实施例12盐酸维拉佐酮软胶囊的制备
按照实施例6的配方制备盐酸维拉佐酮软胶囊,其步骤如下:
1)囊壳液的制备:称取明胶,甘油,水,混合均匀,80℃水浴加热溶解,加入对羟基苯甲酸甲酯经搅拌,抽真空脱气后,70℃保温备用;
2)囊壳内容物的制备:称取盐酸维拉佐酮固体分散体4g、聚乙二醇、甘油、羟丙基甲基纤维素、抗坏血酸、对羟基苯甲酸甲酯,混合均匀,备用;
3)将上述的囊壳内容物与囊壳装入自动旋转轧囊机中,温度控制在40-50℃,制备成盐酸维拉佐酮软胶囊。
运用本发明提供的方法与配方制成的盐酸维拉佐酮软胶囊,溶出率高,吸收利用效果好。
在不偏离本发明精神的基础上所做的这些修改或改进,均属于本发明要求保护的范围。
Claims (9)
1.一种盐酸维拉佐酮软胶囊,所述软胶囊包括囊壳和内容物,按重量份,其原料包括如下组分:
囊壳:明胶10份、甘油3.5-4.5份、水10份、防腐剂1.0-3.5份;
内容物:盐酸维拉佐酮1-10份、稀释剂40-90份、助悬剂1-5份、抗氧剂0-3份、防腐剂0-3份;
所述囊壳和内容物的重量比为2:5。
2.根据权利要求1所述的盐酸维拉佐酮软胶囊,其特征在于,所述稀释剂包括聚乙二醇类或植物油的一种或两种,所述聚乙二醇类选自聚乙二醇400、聚乙二醇2000,植物油选自玉米油、大豆油、花生油、麻油、橄榄油、葵花籽油、色拉油、棉籽油或菜籽油;所述稀释剂优选为聚乙二醇400、聚乙二醇2000。
3.根据权利要求1所述的盐酸维拉佐酮软胶囊,其特征在于,所述助悬剂包括乙基羟乙基纤维素、甲壳糖、甲基纤维素、乙基纤维素、琼脂、羟乙基甲基纤维素、羟乙基纤维素、羟丙基甲基纤维素、羟丙基纤维素、苯甲酸、聚乙二醇中一种或几种,所述助悬剂优选为乙基纤维素、羟丙基甲基纤维素。
4.根据权利要求1所述的盐酸维拉佐酮软胶囊,其特征在于,所述抗氧剂包括亚硫酸氢钠、焦亚硫酸钠、焦亚硫酸钾、乙二胺四乙酸、枸橼酸、苹果酸、抗坏血酸、肌醇中的一种或几种,所述抗氧剂优选为抗坏血酸、乙二胺四乙酸。
5.根据权利要求1所述的盐酸维拉佐酮软胶囊,其特征在于,所述防腐剂A包括山梨酸、对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯中一种或几种,所述防腐剂优选对羟基苯甲酸甲酯、山梨酸。
6.根据权利要求1所述的盐酸维拉佐酮软胶囊,其特征在于,所述内容物中还加入了潜溶剂,所述潜溶选自乙醇、甘油或丙二醇,所述潜溶剂的添加量按重量份为1-5份。
7.根据权利要求1所述的盐酸维拉佐酮软胶囊,其特征在于,所述固体分散体载体包括聚乙二醇6000、丙烯酸树脂。
8.根据权利要求1-7任一项所述的盐酸维拉佐酮软胶囊,其特征在于,按重量份,其原料包括如下组分:
囊壳:明胶10份、甘油3.5-4.5份、水10份,对羟基苯甲酸甲酯1.0-3.5份;
内容物:盐酸维拉佐酮1-10份,稀释剂聚乙二醇400 50-70份,助悬剂甲壳糖1-4份、羟丙基甲基纤维素1-4份,抗氧剂抗坏血酸1-2份,防腐剂对羟基苯甲酸甲酯1-2份;
所述囊壳和内容物的重量比为2:5。
9.权利要求1-8任一项所述盐酸维拉佐酮软胶囊的制备方法,包括如下步骤:
囊壳液的制备:称取明胶,甘油,水,混合均匀,80℃水浴加热溶解,加入对羟基苯甲酸甲酯经搅拌,抽真空脱气后,70℃保温备用;
囊壳内容物的制备:称取盐酸维拉佐酮固体分散体4g、聚乙二醇、甘油、羟丙基甲基纤维素、抗坏血酸、对羟基苯甲酸甲酯,混合均匀,备用;
将上述的囊壳内容物与囊壳装入自动旋转轧囊机中,温度控制在40-50℃,制备成盐酸维拉佐酮软胶囊。
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