WO2023016495A1 - 含有白果内酯和大麻二酚的药物组合物及其在医药上的应用 - Google Patents

含有白果内酯和大麻二酚的药物组合物及其在医药上的应用 Download PDF

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WO2023016495A1
WO2023016495A1 PCT/CN2022/111484 CN2022111484W WO2023016495A1 WO 2023016495 A1 WO2023016495 A1 WO 2023016495A1 CN 2022111484 W CN2022111484 W CN 2022111484W WO 2023016495 A1 WO2023016495 A1 WO 2023016495A1
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pharmaceutically acceptable
cannabidiol
bilobalide
pharmaceutical composition
stereoisomers
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PCT/CN2022/111484
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French (fr)
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张靖
魏用刚
王美微
高志文
孙毅
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成都百裕制药股份有限公司
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Priority to CN202280054096.2A priority Critical patent/CN117897154A/zh
Publication of WO2023016495A1 publication Critical patent/WO2023016495A1/zh

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    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/20—Hypnotics; Sedatives

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  • the application generally belongs to the field of medicine, and specifically relates to a pharmaceutical composition containing bilobalide and cannabidiol and its application in medicine.
  • Ginkgo is an important traditional Chinese medicine in my country, and its medical value has attracted widespread attention at home and abroad.
  • Scholars at home and abroad have conducted extensive research on the chemistry, pharmacology, and preparations of Ginkgo biloba, and developed a series of drugs on this basis.
  • Bilobalide is an important component of Ginkgo biloba extract, and it is the only sesquiterpene lactone compound found in Ginkgo biloba. Pharmacological and clinical studies have shown that bilobalide has the effects of neuron protection, nerve function repair and reconstruction, and has a protective effect on the central nervous system.
  • Marijuana (Cannabis sativa L.) is an annual herb of the genus Moraceae, which originated in Central and East Asia and is widely distributed in the United States, India, Brazil and other places. Cannabis has a long history of medicinal use, but its addictive and hallucinogenic effects have greatly limited its clinical application. Cannabis contains hundreds of different chemical substances, about 70 kinds of ingredients are called cannabinoids, mainly including cannabidiol (CBD), cannabinol (CBN), tetrahydrocannabinol (Tetrahydrocannabinol, THC) and its homologues, etc. Among them, cannabidiol (CBD) has the highest content. CBD has a wide range of pharmacological activities.
  • CBD cannabidiol
  • cannabinoid-related drugs have been developed successively, for example; GW Pharmaceuticals' cannabinoid oral mucosal spray (Sative), which is used to treat multiple sclerosis spasticity, another cannabinoid oral solution (Epidiolex ) for the treatment of childhood onset epilepsy.
  • Sative cannabinoid oral mucosal spray
  • Epidiolex another cannabinoid oral solution
  • the present invention provides a pharmaceutical composition of bilobalide and cannabidiol, as well as its use in the preparation of medicines.
  • One or more embodiments of the present application provide a pharmaceutical composition
  • a pharmaceutical composition comprising bilobalide or its stereoisomers, hydrates, metabolites, solvates, pharmaceutically acceptable salts or co-crystals, and cannabidiol Or its stereoisomer, hydrate, metabolite, solvate, pharmaceutically acceptable salt or co-crystal.
  • the bilobalide or its stereoisomer, hydrate, metabolite, solvate, pharmaceutically acceptable salt or co-crystal and cannabidiol or its stereoisomer The weight ratio of hydrate, metabolite, solvate, pharmaceutically acceptable salt or co-crystal is 1:(0.1-10).
  • the bilobalide or its stereoisomer, hydrate, metabolite, solvate, pharmaceutically acceptable salt or co-crystal and cannabidiol or its stereoisomer The weight ratio of hydrate, metabolite, solvate, pharmaceutically acceptable salt or co-crystal is 1:0.1, 1:0.2, 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9 or 1:10.
  • the bilobalide or its stereoisomer, hydrate, metabolite, solvate, pharmaceutically acceptable salt or co-crystal and cannabidiol or its stereoisomer The weight ratio of hydrate, metabolite, solvate, pharmaceutically acceptable salt or co-crystal is 1:(0.8-1.2).
  • the bilobalide or its stereoisomer, hydrate, metabolite, solvate, pharmaceutically acceptable salt or co-crystal and cannabidiol or its stereoisomer The weight ratio of hydrate, metabolite, solvate, pharmaceutically acceptable salt or co-crystal is 1:(0.9-1.1).
  • the bilobalide or its stereoisomer, hydrate, metabolite, solvate, pharmaceutically acceptable salt or co-crystal and cannabidiol or its stereoisomer The weight ratio of hydrate, metabolite, solvate, pharmaceutically acceptable salt or co-crystal is 1:1.
  • the pharmaceutical composition of the present application also includes:
  • One or more embodiments of the present application provide the use of the pharmaceutical composition of the present application in the preparation of sedative drugs.
  • One or more embodiments of the present application provide the use of the pharmaceutical composition of the present application in the preparation of a medicament for preventing and/or treating a disease or condition related to a non-sedated state.
  • “Pharmaceutical composition” refers to a mixture of one or more compounds of the present invention, their pharmaceutically acceptable salts and other chemical components, wherein “other chemical components” refer to pharmaceutically acceptable carriers , excipients, and/or one or more other therapeutic agents.
  • Stepoisomer refers to isomers produced by different arrangements of atoms in a molecule in space, including cis-trans isomers, enantiomers and conformational isomers.
  • “Pharmaceutically acceptable salt” or “pharmaceutically acceptable salt thereof” means that the compound of the present invention maintains the biological effectiveness and characteristics of free acid or free base, and the free acid is mixed with a non-toxic inorganic base or Organic base, the salt obtained by reacting the free base with a non-toxic inorganic acid or organic acid.
  • Co-crystal refers to a crystal formed by combining the active pharmaceutical ingredient and the co-crystal former under the action of hydrogen bonding or other non-covalent bonds, wherein the pure state of API and CCF are solid at room temperature, and each component There is a fixed stoichiometric ratio between them.
  • a co-crystal is a multi-component crystal, including a binary co-crystal formed between two neutral solids, and a multi-component co-crystal formed between a neutral solid and a solvate.
  • Carrier refers to a material that does not produce significant irritation to an organism and that does not abrogate the biological activity and properties of the administered compound.
  • Excipient refers to an inert substance added to a pharmaceutical composition to facilitate administration of the compound.
  • Non-limiting examples include calcium carbonate, calcium phosphate, sugars, starches, cellulose derivatives (including microcrystalline cellulose), gelatin, vegetable oils, polyethylene glycols, diluents, granulating agents, lubricants, binders agents and disintegrants.
  • Optional or “optionally” or “optional” or “optionally” means that the subsequently described event or circumstance may, but need not, occur, and that the description includes the circumstances in which the event or circumstance occurs and the circumstances in which it is not what happened.
  • heterocyclyl optionally substituted with an alkyl group means that the alkyl group may but need not be present, and the description includes cases where the heterocyclyl group is substituted with an alkyl group, and cases where the heterocyclyl group is not substituted with an alkyl group.
  • Figure 1 shows the onset time of sedation in each group.
  • Figure 2 shows the duration of sedation for each group.
  • the pharmaceutical composition is prepared according to the following components and weight ratio: (1) bilobalide, (2) cannabidiol; the weight ratio of bilobalide to cannabidiol is 1:0.8.
  • the pharmaceutical composition is prepared according to the following components and weight ratio: (1) bilobalide, (2) cannabidiol; the weight ratio of bilobalide to cannabidiol is 1:0.9.
  • the pharmaceutical composition is prepared according to the following components and weight ratio: (1) bilobalide, (2) cannabidiol; the weight ratio of bilobalide to cannabidiol is 1:1.
  • the pharmaceutical composition is prepared according to the following components and weight ratio: (1) bilobalide, (2) cannabidiol; the weight ratio of bilobalide to cannabidiol is 1:1.1.
  • the pharmaceutical composition is prepared according to the following components and weight ratio: (1) bilobalide, (2) cannabidiol; the weight ratio of bilobalide to cannabidiol is 1:1.2.
  • the pharmaceutical composition is prepared according to the following components and weight ratio: (1) bilobalide, (2) cannabidiol, (3) optional one or more other active ingredients, (4) pharmaceutically acceptable carrier and/or excipients; the weight ratio of bilobalide to cannabidiol is 1:1.
  • Bilobalide (provided by Chengdu Baiyu Pharmaceutical Co., Ltd., with a content of not less than 98%);
  • Cannabidiol purchased from Ryss Lab, Inc., with a purity of 99% by HPLC;
  • Vehicle DMSO+HS-15+NS (normal saline) (1:1:8, v/v/v).
  • bilobalide and cannabidiol dissolve them in the solvent [DMSO+HS-15+NS (normal saline) (1:1:8, v/v/v)], and prepare the final concentrations of 10mg/ mL of bilobalide solution, 10 mg/mL cannabidiol solution, a composition solution of bilobalide and cannabidiol (containing 10 mg/mL bilobalide and 10 mg/mL cannabidiol).
  • mice After the ICR mice were adapted to the laboratory environment, they were fasted the day before the experiment. On the day of the experiment, 40 animals were selected according to body weight and divided into 4 groups with 10 animals in each group. On the day of grouping, intragastric administration was administered, and the grouping regimen is shown in Table 1 for details.
  • i.g. refers to intragastric administration.
  • Sedation latency period first sedation time point - administration time point, the shorter the sedation onset time, the stronger the sedation effect, the results are shown in Figure 1.

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Abstract

一种药物组合物，其包含白果内酯或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶，以及大麻二酚或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶，该组合物用于预防和/或治疗与非镇静状态相关的疾病或病症。

Description

含有白果内酯和大麻二酚的药物组合物及其在医药上的应用 技术领域
本申请大体上属于医药领域，具体涉及含有白果内酯和大麻二酚的药物组合物及其在医药上的应用。
背景技术
银杏是我国重要的中药，其医用价值已引起国内外的广泛关注，国内外学者对银杏叶的化学、药理、制剂等进行了广泛的研究，并在此基础上开发了一系列药物。白果内酯为银杏叶提取物中一种重要成分，是目前从银杏叶中发现的唯一的一个倍半萜内酯化合物。药理和临床研究表明，白果内酯具有神经元保护、神经功能修复及重构的作用，对中枢神经系统具有保护作用。
大麻(Cannabis sativa L.)为桑科大麻属一年生草本植物，起源于中亚和东亚，广泛分布于美国、印度、巴西等地。大麻的药用历史悠久，但成瘾性和精神致幻作用，使其临床应用受到极大限制。大麻含有数百种不同的化学物质，大约有70多种成分被称为大麻素，主要包括大麻二酚(cannabidiol，CBD)、大麻酚(cannabinol，CBN)、四氢大麻酚(Tetrahydrocannabinol，THC)及其同系物等。其中大麻二酚(CBD)含量最高。CBD具有广泛的药理活性，近年来，大麻素相关药品被陆续开发，例如；GW Pharmaceuticals的大麻素口腔黏膜喷雾剂(Sative)，用于治疗多发性硬化症痉挛，另一个大麻素口服溶液(Epidiolex)用于治疗儿童发作性癫痫。
目前，白果内酯和大麻二酚都是单独使用，发挥各自的药效，将白果内酯与大麻二酚制备成药物组合物尚未见报道。
发明内容
为了满足临床疗效的需要，本发明提供白果内酯与大麻二酚的药物组合物，以及其在制备药物的用途。
本申请的一个或多个实施方式提供了药物组合物，其包含白果内酯或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶，以及大麻二酚或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶。
在一个或多个实施方式中，所述白果内酯或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶与大麻二酚或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶的重量比为1:(0.1～10)。
在一个或多个实施方式中，所述白果内酯或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶与大麻二酚或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶的重量比为1:0.1、1:0.2、1:0.3、1:0.4、1:0.5、1:0.6、1:0.7、1:0.8、1:0.9、1:1、1:2、1:3、1:4、1:5、1:6、1:7、1:8、1:9或1:10。
在一个或多个实施方式中，所述白果内酯或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶与大麻二酚或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶的重量比为1:(0.8～1.2)。
在一个或多个实施方式中，所述白果内酯或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶与大麻二酚或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶的重量比为1:(0.9～1.1)。
在一个或多个实施方式中，所述白果内酯或其立体异构体、水合物、代谢产物、溶剂 化物、药学上可接受的盐或共晶与大麻二酚或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶的重量比为1:1。
在一个或多个实施方式中，本申请的药物组合物还包含：
任选的一种或多种其他活性成分；以及
药学上可接受的载体和/或赋形剂。
本申请的一个或多个实施方式提供了本申请的药物组合物在制备镇静药物中的用途。
本申请的一个或多个实施方式提供了本申请的药物组合物在制备用于预防和/或治疗与非镇静状态相关的疾病或病症的药物中的用途。
发明详述
除非有相反的陈述，在说明书和权利要求书中使用的术语具有下述含义，否则本申请中出现的术语具有本领域中公知的含义。
“药物组合物”是指一种或多种本发明所述化合物、其药学上可接受的盐和其它化学组分形成的混合物，其中，“其它化学组分”是指药学上可接受的载体、赋形剂和/或一种或多种其它治疗剂。
“立体异构体”是指由分子中原子在空间上排列方式不同所产生的异构体，包括顺反异构体、对映异构体和构象异构体。
“药学上可接受的盐”或者“其药学上可接受的盐”是指本发明化合物保持游离酸或者游离碱的生物有效性和特性，且所述的游离酸通过与无毒的无机碱或者有机碱，所述的游离碱通过与无毒的无机酸或者有机酸反应获得的盐。
“共晶”是指活性药物成分和共晶形成物在氢键或其他非共价键的作用下结合而成的晶体，其中API和CCF的纯态在室温下均为固体，并且各组分间存在固定的化学计量比。共晶是一种多组分晶体，既包含两种中性固体之间形成的二元共晶，也包含中性固体与或溶剂化物形成的多元共晶。
“载体”是指不会对生物体产生明显刺激且不会消除所给予化合物的生物活性和特性的材料。
“赋形剂”是指加入到药物组合物中以促进化合物给药的惰性物质。非限制性实施例包括碳酸钙、磷酸钙、糖、淀粉、纤维素衍生物(包括微晶纤维素)、明胶、植物油、聚乙二醇类、稀释剂、成粒剂、润滑剂、粘合剂和崩解剂。
“任选”或“任选地”或“选择性的”或“选择性地”是指随后所述的事件或状况可以但未必发生，该描述包括其中发生该事件或状况的情况及其中未发生的情况。例如，“选择性地被烷基取代的杂环基”是指该烷基可以但未必存在，该描述包括其中杂环基被烷基取代的情况，及其中杂环基未被烷基取代的情况。
附图说明
图1表示各组的镇静出现时间。
图2表示各组的镇静持续时间。
具体实施方式
本发明说明书对具体实施方案进行了详细描述，本领域技术人员应认识到，上述实施方案是示例性的，不能理解为对本发明的限制，对于本领域技术人员来说，在不脱离本发明原理的前提下，通过对本发明进行若干改进和修饰，这些改进和修饰获得技术方案也落在本发明的权利要求书的保护范围内。以下通过实施例具体说明本发明的有益效果。
实施例
实施例1
按照以下组分和重量比制备药物组合物：(1)白果内酯，(2)大麻二酚；所述白果内酯与大麻二酚的重量比为1：0.8。
实施例2
按照以下组分和重量比制备药物组合物：(1)白果内酯，(2)大麻二酚；所述白果内酯与大麻二酚的重量比为1：0.9。
实施例3
按照以下组分和重量比制备药物组合物：(1)白果内酯，(2)大麻二酚；所述白果内酯与大麻二酚的重量比为1：1。
实施例4
按照以下组分和重量比制备药物组合物：(1)白果内酯，(2)大麻二酚；所述白果内酯与大麻二酚的重量比为1：1.1。
实施例5
按照以下组分和重量比制备药物组合物：(1)白果内酯，(2)大麻二酚；所述白果内酯与大麻二酚的重量比为1：1.2。
实施例6
按照以下组分和重量比制备药物组合物：(1)白果内酯，(2)大麻二酚，(3)任选的一种或者多种其他活性成分，(4)药学上可接受的载体和/或赋形剂；所述白果内酯与大麻二酚的重量比为1：1。
活性实施例：白果内酯和大麻二酚的药物组合物对小鼠的镇静作用
1.实验材料
1.1实验动物
SPF级，ICR小鼠，雄性，50只，18-22g。实验动物来源：成都达硕实验动物有限公司。生产许可证号：SCXK(川)2014-028。
1.2实验试剂
白果内酯(成都百裕制药股份有限公司提供，含量不低于98％)；
大麻二酚(购于Ryss Lab,Inc.，HPLC检测纯度为99％)；
溶媒：DMSO+HS-15+NS(生理盐水)(1:1:8，v/v/v)。
2实验方法
2.1供试品配制
称取白果内酯、大麻二酚适量，溶于溶媒[DMSO+HS-15+NS(生理盐水)(1:1:8，v/v/v)]中，配制成终浓度分别为10mg/mL的白果内酯溶液、10mg/mL的大麻二酚溶液、白果内酯和大麻二酚的组合物溶液(含10mg/mL白果内酯和10mg/mL大麻二酚)。
2.2分组及给药
ICR小鼠实验室环境适应后，在实验前一天禁食。实验当天，根据体重筛选40只动物入组，分为4组，每组10只。分组当天灌胃给药，分组给药方案详见表1。
表1给药方案
Figure PCTCN2022111484-appb-000001
注：i.g.指灌胃给药。
3实验指标
3.1镇静潜伏期(镇静出现时间，min)
给药后记录给药时间，观察记录首次出现镇静的时间，计算镇静潜伏期。镇静潜伏期＝首次出现镇静时间点-给药时间点，镇静出现时间越短，表明镇静效果更强，结果见图1。
3.2镇静持续时间(min)
记录2小时内镇静持续的时间。镇静持续时间越长，表明镇静效果越好，结果见图2。
4结果
在小鼠镇静模型中显示，与白果内酯或者大麻二酚单用组相比，白果内酯和大麻二酚联用组镇静起效更快、持续时间更长。

Claims (9)

  1. 药物组合物，其包含白果内酯或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶，以及大麻二酚或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶。
  2. 根据权利要求1所述的药物组合物，其中所述白果内酯或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶与大麻二酚或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶的重量比为1:(0.1～10)。
  3. 根据权利要求1所述的药物组合物，其中所述白果内酯或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶与大麻二酚或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶的重量比为1:0.1、1:0.2、1:0.3、1:0.4、1:0.5、1:0.6、1:0.7、1:0.8、1:0.9、1:1、1:2、1:3、1:4、1:5、1:6、1:7、1:8、1:9或1:10。
  4. 根据权利要求1所述的药物组合物，其中所述白果内酯或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶与大麻二酚或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶的重量比为1:(0.8～1.2)。
  5. 根据权利要求1所述的药物组合物，其中所述白果内酯或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶与大麻二酚或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶的重量比为1:(0.9～1.1)。
  6. 根据权利要求1所述的药物组合物，其中所述白果内酯或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶与大麻二酚或其立体异构体、水合物、代谢产物、溶剂化物、药学上可接受的盐或共晶的重量比为1:1。
  7. 根据权利要求1～6中任一项所述的药物组合物，其还包含：
    任选的一种或多种其他活性成分；以及
    药学上可接受的载体和/或赋形剂。
  8. 权利要求1～7中任一项所述的药物组合物在制备镇静药物中的用途。
  9. 权利要求1～7中任一项所述的药物组合物在制备用于预防和/或治疗与非镇静状态相关的疾病或病症的药物中的用途。
PCT/CN2022/111484 2021-08-13 2022-08-10 含有白果内酯和大麻二酚的药物组合物及其在医药上的应用 WO2023016495A1 (zh)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020081513A1 (en) * 2018-10-16 2020-04-23 Systamedic Inc. Novel compositions for the treatment of inflammatory diseases
US20200138737A1 (en) * 2018-11-02 2020-05-07 Canopy Health Innovations Composition comprising cannabinoids for relief of pain
US20200253921A1 (en) * 2017-10-30 2020-08-13 Endocanna Health, Inc. Cannabinoid Formulations
CN113087741A (zh) * 2020-01-08 2021-07-09 成都百裕制药股份有限公司 大麻二酚衍生物及其制备方法和在医药上的应用
CN113087599A (zh) * 2020-01-08 2021-07-09 成都百裕制药股份有限公司 大麻二酚衍生物及其制备方法和在医药上的应用

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20200253921A1 (en) * 2017-10-30 2020-08-13 Endocanna Health, Inc. Cannabinoid Formulations
WO2020081513A1 (en) * 2018-10-16 2020-04-23 Systamedic Inc. Novel compositions for the treatment of inflammatory diseases
US20200138737A1 (en) * 2018-11-02 2020-05-07 Canopy Health Innovations Composition comprising cannabinoids for relief of pain
CN113087741A (zh) * 2020-01-08 2021-07-09 成都百裕制药股份有限公司 大麻二酚衍生物及其制备方法和在医药上的应用
CN113087599A (zh) * 2020-01-08 2021-07-09 成都百裕制药股份有限公司 大麻二酚衍生物及其制备方法和在医药上的应用

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MA LEIGE, WANG SHIYAN, TAI FADAO, YUAN GANG, WU RUIYONG, LIU XIAO, WEI BIN, YANG XIANGPING: "Effects of bilobalide on anxiety, spatial learning, memory and levels of hippocampal glucocorticoid receptors in male Kunming mice", PHYTOMEDICINE, ELSEVIER, AMSTERDAM, NL, vol. 20, no. 1, 1 December 2012 (2012-12-01), AMSTERDAM, NL , pages 89 - 96, XP093035044, ISSN: 0944-7113, DOI: 10.1016/j.phymed.2012.09.015 *

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