CN112121176A - 一种顺铂微粒系统组成、制备方法及应用 - Google Patents

一种顺铂微粒系统组成、制备方法及应用 Download PDF

Info

Publication number
CN112121176A
CN112121176A CN201910547554.6A CN201910547554A CN112121176A CN 112121176 A CN112121176 A CN 112121176A CN 201910547554 A CN201910547554 A CN 201910547554A CN 112121176 A CN112121176 A CN 112121176A
Authority
CN
China
Prior art keywords
cisplatin
coo
calculated
preparing
peg
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.)
Granted
Application number
CN201910547554.6A
Other languages
English (en)
Other versions
CN112121176B (zh
Inventor
张震
李军
王维剑
牛冲
董朋伟
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shandong Hubble Kisen Biological Technology Co ltd
Original Assignee
Shandong Hubble Kisen Biological Technology Co ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Shandong Hubble Kisen Biological Technology Co ltd filed Critical Shandong Hubble Kisen Biological Technology Co ltd
Priority to CN201910547554.6A priority Critical patent/CN112121176B/zh
Publication of CN112121176A publication Critical patent/CN112121176A/zh
Application granted granted Critical
Publication of CN112121176B publication Critical patent/CN112121176B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • 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
    • A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6921—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
    • A61K47/6927—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
    • A61K47/6929—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle
    • A61K47/6931—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer
    • A61K47/6935—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/243—Platinum; Compounds thereof
    • 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
    • A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nanotechnology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

本发明涉及一种成本更低，但具有较高顺铂载药量及屏蔽巨噬细胞吞噬效果的顺铂微粒系统组成及制备方法。以甲氧基聚乙二醇2000‑聚谷氨酸钠共聚物(MPEG2000‑P(GluNa)2000)为载体与顺铂在专利要求的制备方法条件下，制备的顺铂纳米粒具有更高的载药量，体内血循环过程中，能够更好地屏蔽巨噬细胞的吞噬，具有更好的肿瘤组织分布。

Description

一种顺铂微粒系统组成、制备方法及应用
发明领域
本发明属于药物技术领域，具体涉及一种成本更低，但具有较高顺铂载药量及屏蔽巨噬细胞吞噬效果的微粒系统组成及制备方法。
背景技术
顺铂(顺式二氯二氨合铂，CISP)是1965年由美国科学家Rosenborg等人发现的第一个具有抗癌活性的金属配合物，属于细胞非特异性药物。顺铂作为一种广谱的抗癌药物，对许多癌症，如乳腺癌、卵巢癌、宫颈癌、食道癌、非小球细胞肺癌和胃癌等在临床中具有疗效确切、抗癌活性高等特点，但其严重的肾毒性、听觉衰减等毒副作用限制了顺铂及其铂类化合物在临床上的广泛应用。人体肾脏对外来异物粒径的清除阈值在5.5nm左右，大于5.5nm 的粒子不会被肾脏清除。Kataoka及其同事报道30nm以上的颗粒对渗透性较差的肿瘤疗效较差(Nat Nanotechnol,2011)，Jain等人也证实粒径为12nm的纳米制剂对渗透性较差的肿瘤具有较好的渗透性(Nat Nanotechnol,2012)。
发明内容
NC-6004是日本Nanocarrier公司开发的顺铂聚合物纳米胶束，它降低了顺铂的肾毒性，目前在美国进行III期临床试验。NC-6004是采用聚乙二醇-聚谷氨酸嵌段聚合物(见式1)
Figure BDA0002104448130000011
与顺铂发生配位反应制备的纳米药物。但是，NC-6004顺铂载药量仅为39％，且其选用的载体为甲氧基聚乙二醇12000-聚谷氨酸钠6000(MPEG12000-P(GluNa)6000)，其亲水段MPEG12000，成本远高于甲氧基聚乙二醇2000，此外我们通过分析吸附在由两种亲水段载体制备的纳米粒上的蛋白，也发现MPEG2000形成的微粒所形成的的“蛋白冠”中蛋白的种类与MPEG12000 有不同，其被巨噬细胞吞噬的程度也不同。
我们申请保护的甲氧基聚乙二醇2000和聚谷氨酸苄酯羧酸酐聚合而成的甲氧基聚乙二醇2000-聚谷氨酸钠共聚物(MPEG2000-P(GluNa)2000)，在共聚物中氧烯单元(m)为43～48，谷氨酸钠单元(n)为11～15，其平均分子量为3600～4400。而NC-6004所用的载体为甲氧基聚乙二醇12000-聚谷氨酸钠6000共聚物MPEG12000-P(GluNa)6000，其共聚物中氧烯单元(m)为258～288，谷氨酸钠单元(n)为33～45；在等质量的条件下，我们MPEG2000-P(GluNa)2000所带有的COO-摩尔数要高于MPEG12000-P(GluNa)6000，因此我们所制备的顺铂微粒系统载药量可达42％以上，高于NC-6004的39％。此外MPEG12000成本远高于我们的MPEG2000，并且我们通过液质对由MPEG2000-P(GluNa)2000和MPEG12000-P(GluNa)6000与顺铂组成的纳米粒与血浆孵化，对其形成的“蛋白冠”进行蛋白分析，发现其蛋白谱也不同，而蛋白谱不同，直接会影响纳米粒在体内的分布、药效，通过实验结果对比，表明我们的MPEG2000-P(GluNa) 2000制备的顺铂纳米粒具有更好的蛋白屏蔽效果。此外，PEG属于非生物降解材料，PEG分子量越大，其降解速度越慢，对于肿瘤这种长期用药疾病，PEG在体内长期积累会带来诸多未知毒副作用。
另一方面，我们发明提供了三种制备顺铂纳米药物的方法，要不同且优于专利CN1476330，CN10207634所述制备方法，具体方法如下：
方法一：
Figure 100002_DEST_PATH_IMAGE001
AgNO3：PEG-PGlu-Na(以COO-计)的摩尔比(即Ag+/COO-)为1：1以上，顺铂(以 Cl-计)：PEG-PGlu-Ag(以Ag+计)的摩尔比(即Cl-/Ag+)为1：1以上。
方法二：
Figure 100002_DEST_PATH_IMAGE002
AgNO3：顺铂(以Cl-计)的摩尔比(即Ag+/Cl-)为1：1以上，硝酸铂(以NO3 -计)： PEG-PGlu-Na(以COO-计)的摩尔比(即NO3 -/COO-)为1：1以上。
方法三：
Figure DEST_PATH_IMAGE003
AgNO3：顺铂(以Cl-计)：PEG-PGlu-Na(以COO-计)的摩尔比(即Ag+/Cl-/COO-)为 1～3:1～1.5:1。
此外，所述的微粒系统制备方法，该方法的反应温度为25℃～60℃，条件均在避光条件下反应，反应时间为4～72小时。
由上述方法及本发明后续实施例可以知道，本发明负载顺铂的微粒系统，具有以下特点：
1)本发明负载顺铂所用载体为MPEG2000-P(GluNa)2000，区别现有任何文献专利报道所采用的嵌段比。
2)本发明负载顺铂所用载体为MPEG2000-P(GluNa)2000，所采用的MPEG2000具有更好的生物相容性及蛋白屏蔽效果。
3)本发明提供的顺铂微粒系统，具有更高的载药量，更低的成本。
4)本发明提供的顺铂微粒制备工艺，简单、高效、收率更高。
综上所述，本发明提供一种成本更低、及较好屏蔽巨噬细胞吞噬效果的微粒系统组成；并且所提供的制备方法具有更高载药、更高收率优势。
附图说明
附图1MPEG2000-P(GluNa)2000顺铂纳米粒(HK038)冻干粉、负载顺铂纳米粒水溶液
附图2MPEG2000-P(GluNa)2000顺铂纳米粒(HK038)水溶液的粒径分布图；
附图3MPEG2000-P(GluNa)2000顺铂纳米粒(HK038)水溶液透射电镜图；
附图4MPEG2000-P(GluNa)2000顺铂纳米粒(HK038)与MPEG12000-P(GluNa)6000(NC6004)与血浆孵化，通过质谱检测得所吸附的蛋白量。
附图5顺铂纳米粒HK038与比较例NC-6004在体内组织分布示意图(A)肝，(B)肿瘤
具体实施方式
下面将结合具体实施例详细阐述本发明。应理解，这些实施例仅用于阐述和解释本发明，而并不限制本发明的范围。下列实施例中未注明具体条件的实验方法，通常按照本领域的常规条件或制造厂商所建议的条件。
实施例1
称取MPEG2000-P(GluNa)2000约38.85mg，硝酸银48mg，置100m圆底烧瓶中，加30ml 蒸馏水，40℃水浴振荡反应10小时；离心除掉上清液，收集沉淀物，再用30ml纯化水分散沉淀物，加入顺铂原料45mg，置40℃水浴振荡反应96小时；待沉淀物全部溶解后，取溶液用10KDa超滤离心，进行浓缩，将浓缩后液体合并后，过0.22μm滤膜后分装冻干。
实施例2
称取顺铂原料45mg，硝酸银48mg，加30ml蒸馏水，37℃水浴振荡反应4小时；离心取上清液，而后加入MPEG2000-P(GluNa)2000约38.85mg，置圆底烧瓶中，振摇使溶解，置37℃水浴振荡反应72小时；而后10KDa超滤离心，进行浓缩，将浓缩液多次清洗，将浓缩后液体合并后，过0.22μm滤膜后分装冻干。
实施例3
称取顺铂原料149mg，硝酸银161.5mg，MPEG2000-P(GluNa)2000 298mg置100m圆底烧瓶中，加50ml蒸馏水，37℃水浴振荡反应4～10小时；过滤，除去氯化银，取续滤液10KDa 超滤离心进行浓缩；将浓缩后液体分装冻干。
实施例4
称取顺铂原料45mg，硝酸银48mg，加30ml蒸馏水，50℃水浴振荡反应2小时；离心后，除去氯化银，将续滤液加入MPEG2000-P(GluNa)2000约38.85mg，振摇使溶解，置50℃水浴振荡反应72小时；取续滤液10KDa超滤离心进行浓缩；将浓缩后液体分装冻干。
以下为比较例：
比较例1
参考专利CN1476330，CN10207634所述制备方法：
取顺铂70mg溶解于注射用水而形成的溶液，而后加入MPEG12000-P(GluNa)6000共聚物 105mg，加入注射用水使总量达到50mL。使该溶液在37℃反应3天。而后10KDa超滤离心进行浓缩；将浓缩后液体分装冻干。
对各实施例及比较例制备的样品进行测定，结果如下：
批号 顺铂含量 平均粒径nm 包封率％
实施例1 43.14 26.7 89.06
实施例2 42.37 27.5 88.96
实施例3 42.91 26.5 89.32
实施例4 43.02 28.6 88.55
比较例1 38.98 27.4 83.21
说明采用我们专利方法制备的顺铂微粒具有更高的载药量和包封率。
血浆蛋白吸附实验：
以实施例1所制备顺铂纳米粒(HK038)与比较例1制备顺铂纳米粒(NC-6004)为样品，考察其在血浆中对蛋白的吸附数量及区别。
取健康人血，加入肝素防止凝结，以标准结晶牛血清清蛋白(BSA)为标准蛋白溶液，采用Thermo Pierce的660nm Protein Assay确定蛋白浓度66mg/ml。为剔除可能聚集的蛋白，在使用前20000g转离心1h。取相同质量的HK038和NC-6004超纯水复溶后，在相同体积的表面皿血浆中加入相同质量的纳米粒子，37℃孵化1h，而后将通过20000g离心1h收集纳米粒子，将纳米粒子用PBS再分散、冲洗、再离心(20000g离心1h)，收集再分散，重复6 次。而后分散液转移新的EP管中，吸附在纳米粒子的蛋白通过加入300ul 7Murea(尿素),2Mthiourea(硫脲),4％CHAPS(3-[(3-胆固醇氨丙基)二甲基氨基]丙磺酸)缓冲液洗脱下来，通过Thermo Pierce的660nm Protein Assay测定。结果见附图3，HK038所吸附的蛋白数量少于 NC-6004，说明MPEG2000的蛋白屏蔽效果优于MPEG12000。这对顺铂纳米粒子体内躲避巨噬细胞的吞噬无疑是有利的。
静脉给药组织分布研究
取生长良好的鼠源乳腺癌4T1细胞，通过细胞计数法，用生理盐水调整细胞浓度为6×106/mL，每只健康Balb/C小鼠皮下处接种0.2mL，含1.2×106个细胞，正常饲养7天，观察成瘤，当肿瘤体积长到150mm3时，将18只荷瘤Balb/C小鼠随机分成两组，每组9只，分别为HK038 组(4mg/kg)，NC-6004(4mg/kg)组。
HK038与NC-6004临用前用葡萄糖注射液稀释溶解。小鼠给药剂量均为4mg/kg，以顺铂计。两组实验动物分别尾静脉注射HK038与NC-6004溶液，于给药后2、6、12h各断颈处死3 只小鼠，取肝、肿瘤等组织处理，采用ICP-MS测定Pt含量，将结果见附图4。

Claims (7)

1.一种成本更低，但具有较高顺铂载药量及屏蔽巨噬细胞吞噬效果的微粒系统组成及制备方法。其含有式I表示的嵌段共聚物与顺铂通过配位反应制备的微粒系统，特征在于：该嵌段共聚物亲水嵌段由均分子量2000的甲氧基聚乙二醇组成，疏水嵌段由分子量1500～4000的聚谷氨酸钠组成。
Figure FDA0002104448120000011
甲氧基聚乙二醇2000和聚谷氨酸苄酯羧酸酐聚合而成的甲氧基聚乙二醇-聚谷氨酸钠共聚物，在共聚物中氧烯单元(m)为43～48，谷氨酸钠单元(n)为11～15。
2.根据权利要求1所述的微粒系统组成，其特征在于：所述的微粒系统组成进一步含有冻干用的赋形剂，优选甘露醇、蔗糖、乳糖、山梨醇、葡萄糖。
3.根据权利要求1所述的微粒系统制备方法，其特征在于可通过下列任何化学反应制备：
方法一：
Figure DEST_PATH_IMAGE001
方法二：
Figure DEST_PATH_IMAGE002
方法三：
Figure FDA0002104448120000021
4.根据权利要求3所述的微粒系统制备方法，该方法的反应温度为25℃～60℃，条件均在避光条件下反应，反应时间为4～72小时。
5.根据权利要求3所述的微粒系统制备方法，其中方法一：AgNO3：PEG-PGlu-Na(以COO-计)的摩尔比(即Ag+/COO-)为1：1以上，顺铂(以Cl-计)：PEG-PGlu-Ag(以Ag+计)的摩尔比(即Cl-/Ag+)为1：1以上。
6.根据权利要求3所述的微粒系统制备方法，其中方法二：AgNO3：顺铂(以Cl-计)的摩尔比(即Ag+/Cl-)为1：1以上，硝酸铂(以NO3 -计)：PEG-PGlu-Na(以COO-计)的摩尔比(即NO3 -/COO-)为1：1以上。
7.根据权利要求3所述的微粒系统制备方法，其中方法三：AgNO3：顺铂(以Cl-计)：PEG-PGlu-Na(以COO-计)的摩尔比(即Ag+/Cl-/COO-)为1～3:1～1.5:1。
CN201910547554.6A 2019-06-24 2019-06-24 一种顺铂微粒组成、制备方法及应用 Active CN112121176B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201910547554.6A CN112121176B (zh) 2019-06-24 2019-06-24 一种顺铂微粒组成、制备方法及应用

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201910547554.6A CN112121176B (zh) 2019-06-24 2019-06-24 一种顺铂微粒组成、制备方法及应用

Publications (2)

Publication Number Publication Date
CN112121176A true CN112121176A (zh) 2020-12-25
CN112121176B CN112121176B (zh) 2022-07-01

Family

ID=73849392

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201910547554.6A Active CN112121176B (zh) 2019-06-24 2019-06-24 一种顺铂微粒组成、制备方法及应用

Country Status (1)

Country Link
CN (1) CN112121176B (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115197433A (zh) * 2022-09-13 2022-10-18 山东华铂凯盛生物科技有限公司 一种纳米药物载体甲氧基聚乙二醇-聚（l-谷氨酸钠）的制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1476330A (zh) * 2000-09-26 2004-02-18 ��ʽ�����ȶ˿�ѧ������������ 包封顺铂的高分子微胶粒及其用途
US20110110881A1 (en) * 2008-06-24 2011-05-12 Kazunori Kataoka Liquid composition of cisplatin coordination compound
CN102863627A (zh) * 2012-10-10 2013-01-09 中国科学院长春应用化学研究所 顺铂配合物及其制备方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1476330A (zh) * 2000-09-26 2004-02-18 ��ʽ�����ȶ˿�ѧ������������ 包封顺铂的高分子微胶粒及其用途
US20110110881A1 (en) * 2008-06-24 2011-05-12 Kazunori Kataoka Liquid composition of cisplatin coordination compound
CN102863627A (zh) * 2012-10-10 2013-01-09 中国科学院长春应用化学研究所 顺铂配合物及其制备方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
YU, HAIYANG等: "Cisplatin loaded poly(L-glutamic acid)-g-methoxy poly(ethylene glycol) complex nanoparticles for potential cancer therapy: preparation, in vitro and in vivo evaluation", 《JOURNAL OF BIOMEDICAL NANOTECHNOLOGY》 *
汤朝晖，陈学思: "聚谷氨酸接枝聚乙二醇抗肿瘤药物靶向输送系统", 《高分子学报》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115197433A (zh) * 2022-09-13 2022-10-18 山东华铂凯盛生物科技有限公司 一种纳米药物载体甲氧基聚乙二醇-聚（l-谷氨酸钠）的制备方法
CN115197433B (zh) * 2022-09-13 2023-01-24 山东华铂凯盛生物科技有限公司 一种纳米药物载体甲氧基聚乙二醇-聚（l-谷氨酸钠）的制备方法

Also Published As

Publication number Publication date
CN112121176B (zh) 2022-07-01

Similar Documents

Publication Publication Date Title
CN106821985B (zh) 一种适配体修饰的携氧载药多功能脂质体复合物
US10517961B2 (en) Drug formulation based on particulates comprising polysaccharide-vitamin conjugate
CN110368374A (zh) 一种抗肿瘤铂类药物矿化蛋白纳米粒及其制备方法和应用
CN114377149B (zh) 一种Mn基可降解MOF纳米反应器及其制备方法和应用
CN110623925B (zh) 一种雷帕霉素纳米缓释剂及其制备方法
CN101254309A (zh) 叶酸受体介导靶向乙酰普鲁兰多糖纳米粒及制备方法
US20200392296A1 (en) Nano coordination polymer and preparation method and application thereof
CN114569577B (zh) 一种聚合物包衣纳米粒及其制备方法
CN107019673A (zh) 一种具有肿瘤主动靶向功能的紫杉醇脂质体制剂及其制备方法和应用
Huang et al. Cytomembrane-mimicking nanocarriers with a scaffold consisting of a CD44-targeted endogenous component for effective asparaginase supramolecule delivery
CN106667963B (zh) Rgd及peg共修饰的pamam树状大分子载三氧化二砷递药系统的制备方法
CN112121176B (zh) 一种顺铂微粒组成、制备方法及应用
CN103976976A (zh) 一种包载重组人生长激素缓释药物微囊的制法
CN104784700B (zh) 一种药物共载复合物、胶束及胶束的制备方法
CN112603908B (zh) 一种基于氨基酸聚合物的纳米载药体系及其制备方法和应用
CN108938663A (zh) 1,2-二羧酸单酰胺聚合物作为化疗的增效剂
CN107007550B (zh) 一种氧化还原响应性两亲性共聚物及其制备方法和应用
CN112569367B (zh) 一种5-氟尿嘧啶-介孔二氧化硅-海藻酸钠药物传递系统及其制备方法
CN113651959A (zh) 一种基于氨基酸-羟基酸共聚物的纳米载药体系及其制备方法和应用
CN111743861A (zh) 靶向三阴性乳腺癌的低氧响应手性药物胶束及其制备方法
CN109481400B (zh) 一种肝靶向阿霉素/Bcl-2 siRNA共载纳米胶束及其制备方法和应用
CN103041403A (zh) 含葡聚糖的药物组合物及其制备方法
CN107412786A (zh) 一种基因载体系统的制备与应用
CN109276720B (zh) 一种金属-有机物配合物纳米材料及其制备方法和应用
CN116077460A (zh) 一种负载化疗药物的灵芝多糖纳米粒

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
CB03 Change of inventor or designer information
CB03 Change of inventor or designer information

Inventor after: Wang Cheng

Inventor after: Zhang Zhen

Inventor after: Li Jun

Inventor after: Wang Weijian

Inventor after: Niu Chong

Inventor after: Dong Pengwei

Inventor before: Zhang Zhen

Inventor before: Li Jun

Inventor before: Wang Weijian

Inventor before: Niu Chong

Inventor before: Dong Pengwei

GR01 Patent grant
GR01 Patent grant