BR112017001623B1 - Sal de adição ácido-base em uma forma substancialmente pura, composição farmacêutica compreendendo uma quantidade do referido sal e seus usos - Google Patents

Sal de adição ácido-base em uma forma substancialmente pura, composição farmacêutica compreendendo uma quantidade do referido sal e seus usos Download PDF

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Publication number
BR112017001623B1
BR112017001623B1 BR112017001623-0A BR112017001623A BR112017001623B1 BR 112017001623 B1 BR112017001623 B1 BR 112017001623B1 BR 112017001623 A BR112017001623 A BR 112017001623A BR 112017001623 B1 BR112017001623 B1 BR 112017001623B1
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Brazil
Prior art keywords
acid
liver
berberine
disease
diseases
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BR112017001623-0A
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English (en)
Portuguese (pt)
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BR112017001623A2 (pt
Inventor
Liping Liu
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Shenzhen Hightide Biopharmaceutical, Ltd
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Publication of BR112017001623A2 publication Critical patent/BR112017001623A2/pt
Publication of BR112017001623B1 publication Critical patent/BR112017001623B1/pt

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
    • C07D455/03—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/07—Retinol compounds, e.g. vitamin A
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
    • A—HUMAN NECESSITIES
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    • 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 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
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    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
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    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
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    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
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    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
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    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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    • A—HUMAN NECESSITIES
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
    • C07D471/14—Ortho-condensed systems
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    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Immunology (AREA)
  • Cardiology (AREA)
  • Urology & Nephrology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Oncology (AREA)
  • Psychology (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Vascular Medicine (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Transplantation (AREA)
  • Hospice & Palliative Care (AREA)
  • Ophthalmology & Optometry (AREA)
  • Communicable Diseases (AREA)
BR112017001623-0A 2014-07-29 2015-07-28 Sal de adição ácido-base em uma forma substancialmente pura, composição farmacêutica compreendendo uma quantidade do referido sal e seus usos BR112017001623B1 (pt)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US201462030147P 2014-07-29 2014-07-29
US201462030140P 2014-07-29 2014-07-29
US62/030,140 2014-07-29
US62/030,147 2014-07-29
US201562128077P 2015-03-04 2015-03-04
US62/128,077 2015-03-04
PCT/CN2015/085350 WO2016015634A1 (en) 2014-07-29 2015-07-28 Berberine salts, ursodeoxycholic salts and combinations, methods of preparation and application thereof

Publications (2)

Publication Number Publication Date
BR112017001623A2 BR112017001623A2 (pt) 2017-11-21
BR112017001623B1 true BR112017001623B1 (pt) 2022-11-29

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BR112017001623-0A BR112017001623B1 (pt) 2014-07-29 2015-07-28 Sal de adição ácido-base em uma forma substancialmente pura, composição farmacêutica compreendendo uma quantidade do referido sal e seus usos

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Country Link
US (4) US10301303B2 (enExample)
EP (1) EP3174874B1 (enExample)
JP (4) JP6917144B2 (enExample)
KR (3) KR20250008786A (enExample)
CN (2) CN110179792A (enExample)
AU (2) AU2015296098B2 (enExample)
BR (1) BR112017001623B1 (enExample)
CA (2) CA3194562A1 (enExample)
DK (1) DK3174874T3 (enExample)
EA (1) EA032971B1 (enExample)
ES (1) ES2835874T3 (enExample)
IL (3) IL294063B2 (enExample)
MX (3) MX373840B (enExample)
NZ (1) NZ728488A (enExample)
SG (1) SG11201700481YA (enExample)
WO (1) WO2016015634A1 (enExample)

Families Citing this family (87)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011140441A2 (en) 2010-05-06 2011-11-10 Children's Hospital Medical Center Methods and systems for converting precursor cells into intestinal tissues through directed differentiation
US10155003B2 (en) 2014-05-05 2018-12-18 The Board Of Regents Of The University Of Texas System Methods and compositions comprising ursolic acid and/or resveratrol for treating diabetes, or cancer
WO2015183794A1 (en) * 2014-05-27 2015-12-03 City Of Hope Tgr5 agonist complexes for treating diabetes and cancer
JP6687544B2 (ja) 2014-05-28 2020-04-22 チルドレンズ ホスピタル メディカル センター 前駆細胞を指向性分化によって胃組織に変換するための方法及びシステム
AU2015296098B2 (en) * 2014-07-29 2019-06-27 Shenzhen Hightide Biopharmaceutical, Ltd. Berberine salts, ursodeoxycholic salts and combinations, methods of preparation and application thereof
US11584916B2 (en) 2014-10-17 2023-02-21 Children's Hospital Medical Center Method of making in vivo human small intestine organoids from pluripotent stem cells
CN108137575A (zh) * 2015-04-06 2018-06-08 深圳君圣泰生物技术有限公司 熊去氧胆酸与小檗碱或左旋肉碱的共轭化合物和其组合物及其方法
US12137716B2 (en) 2015-04-16 2024-11-12 Michael Hudnall Methods of liver disease treatment
CN105168228B (zh) * 2015-11-04 2016-06-22 北京凯因科技股份有限公司 奥贝胆酸和小檗碱的复方组合物及其应用
CN116492339A (zh) * 2015-11-13 2023-07-28 深圳君圣泰生物技术有限公司 一种组合物及其用途、药物制剂
CN105693805A (zh) * 2016-03-15 2016-06-22 合肥华方医药科技有限公司 一种胆酸类小檗碱偶合物的制备及医药用途
CN105801663A (zh) * 2016-03-15 2016-07-27 合肥华方医药科技有限公司 一种熊果酸小檗碱偶合物的制备方法及医药用途
GB201605013D0 (en) * 2016-03-24 2016-05-11 Inst Of Food Res S-methylcysteine sulfoxide for prostate cancer treatment
ITUA20163025A1 (it) 2016-04-29 2017-10-29 Sochim Int S P A Composizione per il trattamento della sindrome dell’ovaio policistico
CN109415685B (zh) 2016-05-05 2023-07-04 儿童医院医疗中心 用于体外制造胃底组织的方法和与其相关的组合物
EP3456328A4 (en) * 2016-05-10 2020-02-26 Shenzhen Hightide Biopharmaceutical., Ltd. Composition, and application and pharmaceutical preparation thereof
WO2017218004A1 (en) * 2016-06-17 2017-12-21 Michael Hudnall Medical food for patients with chronic liver disease
CN105963306B (zh) * 2016-07-05 2018-08-17 福州大学 一种具有协同抗肿瘤转移活性的药物组合物
US10702567B2 (en) 2016-09-14 2020-07-07 Phoenix Biotechnology, Inc. Method and compositions for treating viral infection
US10729735B1 (en) 2016-09-14 2020-08-04 Phoenix Biotechnology, Inc. Method and compostitions for treating coronavirus infection
US10596186B2 (en) 2016-09-14 2020-03-24 Phoenix Biotechnology, Inc. Method and compositions for treating viral infections
ES2874187T3 (es) * 2016-09-14 2021-11-04 Phoenix Biotechnology Inc Método y composiciones para el tratamiento de una infección viral
US10703761B2 (en) * 2016-10-18 2020-07-07 City Of Hope Bile acid receptor modulators and methods of use thereof
SG11201903697WA (en) 2016-11-04 2019-05-30 Childrens Hospital Med Ct Liver organoid compositions and methods of making and using same
NZ753873A (en) 2016-12-05 2023-01-27 Children’S Hospital Medical Center Colonic organoids and methods of making and using same
US10471007B2 (en) * 2016-12-16 2019-11-12 Jeffrey R Olynyk Sublingual therapeutic solutions and methods
IT201700032960A1 (it) * 2017-03-24 2018-09-24 Akademy Pharma S R L Composto nutraceutico per il trattamento dell’eccesso di peso e della moderata ipercolesterolemia e disglicemia
MX2019011678A (es) * 2017-03-28 2020-02-12 IRP Health Pty Ltd Alcaloides de berberina en la prevencion y/o tratamiento de una enfermedad intestinal.
WO2018191673A1 (en) 2017-04-14 2018-10-18 Children's Hospital Medical Center Multi donor stem cell compositions and methods of making same
US20200188327A1 (en) * 2017-04-25 2020-06-18 Buck Institute For Research On Aging Formulations for extending lifespan and healthspan
CN108864077B (zh) 2017-05-12 2020-05-22 深圳君圣泰生物技术有限公司 小檗碱有机酸盐的固体形式及其制备方法
US20210121493A1 (en) * 2017-07-25 2021-04-29 Cedars-Sinai Medical Center Methods for treating liver diseases
EP3664850A4 (en) * 2017-08-11 2021-05-05 Shenzhen Hightide Biopharmaceutical Ltd. METHODS AND COMPOSITIONS FOR TREATMENT OF INFLAMMATORY INTESTINAL DISEASES
JP2020536529A (ja) 2017-10-10 2020-12-17 チルドレンズ ホスピタル メディカル センター 食道組織および／または臓器組成物およびそれを作製する方法
WO2019105780A1 (en) * 2017-11-29 2019-06-06 Basf Se Compositions, their manufacture and use
EP3727394A4 (en) 2017-12-21 2021-09-08 Children's Hospital Medical Center DIGITALIZED HUMAN ORGANOIDS AND METHOD OF USING THEREOF
CN112543635A (zh) 2018-05-29 2021-03-23 Irp健康股份有限公司 硝基咪唑制剂
CA3106634A1 (en) 2018-07-26 2020-01-30 Children's Hospital Medical Center Hepato-biliary-pancreatic tissues and methods of making same
AU2019339410A1 (en) 2018-09-12 2021-04-15 Children's Hospital Medical Center Organoid compositions for the production of hematopoietic stem cells and derivatives thereof
SG11202102204PA (en) 2018-09-25 2021-04-29 Ponce De Leon Health Designated Activity Company Process of making calcium alpha-ketoglutarate
CN109303921B (zh) * 2018-10-30 2021-02-09 中国药科大学 Fxr激动剂与sirt1激动剂联用在制备抗肝纤维化药物中的应用
IT201800011155A1 (it) * 2018-12-17 2020-06-17 S&R Farm S P A uso di una miscela di berberina e resveratrolo per il controllo delle dislipidemie
CN111499626A (zh) * 2019-01-31 2020-08-07 西南大学 一种表小檗碱的合成方法及应用
CN109999034A (zh) * 2019-02-11 2019-07-12 浙江理工大学 肿瘤蛋白tnik激酶靶向天然小分子抑制剂及其应用
WO2020179747A1 (ja) * 2019-03-01 2020-09-10 学校法人慶應義塾 Ｈｉｆ抑制用組成物
CN109806264B (zh) * 2019-04-10 2021-04-02 江苏海钥医药科技有限公司 药物组合物及其应用
JP7610533B2 (ja) 2019-05-31 2025-01-08 チルドレンズ ホスピタル メディカル センター 造血幹細胞の生成および拡大方法
CN112076199A (zh) * 2019-06-13 2020-12-15 谢亚坚 一种降血糖降血脂和降血胆固醇方剂
CN110368392A (zh) * 2019-08-20 2019-10-25 延边大学 科罗索酸在制备抗肝损伤药物或抗肝损伤保健品中的应用
CN112851660B (zh) * 2019-11-12 2022-03-18 广东药科大学 含有小檗碱的酸-碱加成盐、其制备方法及其作为药物的用途
CN111116578B (zh) * 2019-12-26 2021-06-04 深圳市老年医学研究所 去亚甲基小檗碱的制备方法及其应用
KR102150821B1 (ko) * 2020-01-22 2020-09-03 주식회사 에이스바이오메드 간 질환 치료용 또는 치료 효과 증진을 위한 콜히친 복합제제
US11806359B2 (en) 2020-03-31 2023-11-07 Phoenix Biotechnology, Inc. Method and compositions for treating Coronavirus infection
US20230181547A1 (en) * 2020-05-15 2023-06-15 Nguyen Anh VAN Solid lipid nano-composition containing berberine and cinnamonaldehyde effective in treating diabetes, dyslipidemia, and method of preparing the same
WO2021247293A1 (en) * 2020-06-02 2021-12-09 Glykon Technologies Group, Llc Methods and pharmaceutical preparations for elevating ketone utilization
BR112023002457A2 (pt) * 2020-08-12 2023-05-02 Archer Daniels Midland Co Processo para purificar uma composição bruta compreendendo ácido 2,5-furanodicarboxílico, éster de dimetila (fdme)
CN114195851B (zh) * 2020-09-18 2023-04-21 成都贝诺科成生物科技有限公司 一种用于防治肝病的化合物及其药用组合物
KR102636847B1 (ko) * 2020-09-18 2024-02-19 경북대학교 산학협력단 티아민 유도체를 포함하는 이식편대숙주질환 예방 또는 치료용 약학적 조성물
WO2022083713A1 (en) * 2020-10-23 2022-04-28 Shenzhen Hightide Biopharmaceutical Ltd. Compositions of berberine ursodeoxycholate and methods thereof for treating fatty liver disease, diabetes and hyperlipidemia
WO2022161468A1 (en) * 2021-01-28 2022-08-04 Shenzhen Hightide Biopharmaceutical Ltd. Compositions of berberine ursodeoxycholate and methods thereof for treating primary sclerosing cholangitis
CN113143962B (zh) * 2021-05-11 2022-08-05 四川九章生物科技有限公司 一种治疗高脂血症的药物组合物及其制备方法
WO2023027994A1 (en) * 2021-08-23 2023-03-02 Paxmedica, Inc. Methods for treating nervous system disorders with antipurinergic agents
CN113577064B (zh) * 2021-09-09 2023-07-04 浙江中医药大学 一种增强肿瘤免疫的联合用药物组合物及其应用
WO2023074894A1 (ja) * 2021-11-01 2023-05-04 小林製薬株式会社 軟骨再生促進剤
WO2023091173A1 (en) * 2021-11-16 2023-05-25 Michael Hudnall Methods of liver disease treatment
WO2023088463A1 (en) * 2021-11-22 2023-05-25 Shenzhen Hightide Biopharmaceutical Ltd. Compositions and methods of berberine ursodeoxycholate for modulating gut microbiome compositions
CN116178384A (zh) * 2021-11-29 2023-05-30 湖南师范大学 四种小檗碱中短链脂肪酸盐的制备
CN114716498B (zh) * 2022-01-20 2024-01-23 成都贝诺科成生物科技有限公司 一种高稳定性的失碳熊去氧胆酸小檗碱盐晶型及其制备方法
KR20230156533A (ko) * 2022-05-06 2023-11-14 동아대학교 산학협력단 이소퀴놀린 유도체 화합물을 유효성분으로 포함하는 미토파지 활성 촉진용 조성물 및 이의 용도
WO2024006537A1 (en) * 2022-07-01 2024-01-04 Intercept Pharmaceuticals, Inc. Methods for ameliorating cognitive impairment using bile acid derivatives
CN115011661B (zh) * 2022-07-22 2024-06-21 湖南科瑞生物制药股份有限公司 一种3β-熊去氧胆酸的合成方法
KR102828609B1 (ko) * 2022-10-11 2025-07-02 주식회사 알트메디칼 이소퀴놀린 유도체를 유효성분으로 포함하는 파킨슨병의 예방 또는 치료용 조성물
KR20240052403A (ko) * 2022-10-14 2024-04-23 주식회사 알트메디칼 이소퀴놀린 유도체를 유효성분으로 포함하는 말초신경병증의 예방 또는 치료용 조성물
KR20240054685A (ko) * 2022-10-19 2024-04-26 주식회사 알트메디칼 이소퀴놀린 유도체를 유효성분으로 포함하는 멜라스증후군의 예방 또는 치료용 조성물
WO2024120452A1 (en) * 2022-12-07 2024-06-13 Shenzhen Hightide Biopharmaceutical Ltd. Compositions and methods for prophylaxis and treatment of covid-19
TW202432104A (zh) * 2022-12-30 2024-08-16 大陸商深圳君聖泰生物技術有限公司 藥物組合、藥物組合物及其應用
EP4665727A1 (en) * 2023-02-15 2025-12-24 Shenzhen Hightide Biopharmaceutical Ltd. Berberine tauroursodeoxycholate compositions and methods thereof
WO2024179570A1 (en) * 2023-03-01 2024-09-06 Shenzhen Hightide Biopharmaceutical Ltd. Compositions and methods for treating severe hypertriglyceridemia
WO2024222408A1 (zh) * 2023-04-28 2024-10-31 杭州居维叶生物医药有限公司 一种黄连素维生素c盐组合物、制备方法及其应用
WO2024245371A1 (zh) * 2023-05-31 2024-12-05 上海复宏汉霖生物技术股份有限公司 一种组合产品、盐及其用于治疗神经退行性疾病或病症的用途
WO2024245370A1 (zh) * 2023-05-31 2024-12-05 上海复宏汉霖生物技术股份有限公司 一种组合产品、盐及其用途
CN116850186A (zh) * 2023-06-02 2023-10-10 深圳市第二人民医院(深圳市转化医学研究院) 一种多靶点神经元保护剂在防治神经系统退行性疾病中的应用
WO2025053283A1 (ja) * 2023-09-07 2025-03-13 株式会社マイトジェニック ベルベルビン関連化合物
CN117731674A (zh) * 2023-12-14 2024-03-22 成都贝诺科成生物科技有限公司 失碳熊去氧胆酸小檗碱盐在制备预防和/或治疗消化道炎症的药物中的用途
WO2025130826A1 (en) * 2023-12-18 2025-06-26 Institute Of Medicinal Biotechnology, Chinese Academy Of Medical Sciences Compositions and methods for treating cancer
KR20250116419A (ko) * 2024-01-25 2025-08-01 주식회사 알트메디칼 이소퀴놀린 유도체 화합물을 유효성분으로 포함하는 당뇨병성 신증의 예방 또는 치료용 약학적 조성물
CN120267634A (zh) * 2025-04-09 2025-07-08 中国药科大学 一种外泌体融合肝靶向脂质体递药系统及其制备方法和应用

Family Cites Families (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5529075B2 (enExample) * 1971-08-20 1980-07-31
IT1136624B (it) * 1981-05-21 1986-09-03 Erregierre Ind Chim Spa Prodotti di salificazione di acidi colici,processo per la loro preparazione e composizioni terapeutiche che li comprendono come principio attivo
JPS60163897A (ja) 1984-02-06 1985-08-26 Tokyo Tanabe Co Ltd ウルソデオキシコ−ル酸メグルミン塩およびその注射剤
JPS6256192A (ja) 1985-09-06 1987-03-11 Hitachi Ltd 感熱転写材
IT1245889B (it) * 1991-04-12 1994-10-25 Alfa Wassermann Spa Formulazioni farmaceutiche per uso orale gastroresistenti contenenti sali di acidi biliari.
JPH06256192A (ja) 1993-03-05 1994-09-13 Nitsusui Seiyaku Kk 液状薬剤の製造法
FR2796551B1 (fr) * 1999-07-23 2003-07-25 Lipha Nouveaux sels de metformine, leur procede d'obtention et les compositions pharmaceutiques en renfermant
KR20050081477A (ko) 2004-02-13 2005-08-19 켐젠주식회사 암로디핀 담즙산염, 그의 제조방법 및 이를 함유하는경구투여용 약학 조성물
CN1759834B (zh) 2004-09-17 2010-06-23 中国医学科学院医药生物技术研究所 黄连素或其与辛伐他汀联合在制备用于预防或治疗与血脂有关疾病或症状的产品中用途
CN1762367A (zh) 2004-10-18 2006-04-26 孙民富 熊去氧胆酸滴丸的处方及其制作方法
WO2007005644A2 (en) 2005-07-01 2007-01-11 Concert Pharmaceuticals Inc. Novel aryloxypropanamines
WO2007005643A2 (en) 2005-07-01 2007-01-11 Concert Pharmaceuticals Inc. Novel aryloxyphenylpropanamines
BRPI0615972A2 (pt) 2005-07-29 2011-05-31 Concert Pharmaceuticals Inc composto isolado, mistura, composição, item de manufatura, uso de um composto, método para determinar a concentração do composto em uma amostra biológica, kit de diagnóstico e método para avaliar a estabilidade metabólica de um composto
KR101380190B1 (ko) 2005-07-29 2014-04-11 콘서트 파마슈티컬즈, 인크. 벤조 〔ｄ〕〔１,３〕―디옥솔 유도체
WO2007090289A1 (en) * 2006-02-09 2007-08-16 National Research Council Of Canada Combinations of botanical extracts for promoting cardiovascular health
CN100509840C (zh) 2006-05-10 2009-07-08 华中科技大学 浙贝乙素和胆汁酸的衍生物及药物组合物
CN101113149B (zh) * 2006-07-25 2011-04-27 复旦大学 小檗碱类生物碱的脂肪族有机酸盐及其制备方法和应用
AU2008220056B2 (en) * 2007-02-28 2014-05-01 Denka Company Limited Reagent for quantitative determination of small, dense LDLs
JP5647519B2 (ja) * 2007-09-13 2014-12-24 コンサート ファーマシューティカルズ インコーポレイテッド 重水素化カテコールおよびベンゾ［ｄ］［１，３］ジオキソールおよびその誘導体の合成
EP2300028A4 (en) * 2008-05-01 2012-10-17 Afexa Life Sciences Inc PHARMACEUTICAL COMPOSITION COMPRISING EFFICIENT HUANGLIAN (COPTIS SINENSIS) AND KU DING CHA EXTRACTS AS HYPOLIPEMANTS
IT1393095B1 (it) * 2009-02-19 2012-04-11 Prodotti Chimici Alimentari Processo per la sintesi del sale disodico dell'acido ursodesossicolico 3,7-disolfato.
CN102361642A (zh) * 2009-03-17 2012-02-22 爱克森医药公司 用升高的剂量的熊去氧胆酸治疗非酒精性脂肪性肝炎的方法
JP2010246578A (ja) * 2009-04-10 2010-11-04 Utsunomiya Univ 血中コレステロールの検査方法および検査装置
US20100323031A1 (en) * 2009-06-22 2010-12-23 Glykon Technologies Group, Llc Synergistic combination to enhance blood glucose and insulin metabolism
CN101987860B (zh) 2009-08-06 2011-12-14 中山百灵生物技术有限公司 一种熊去氧胆酸的制备方法
CN101879162A (zh) * 2010-02-23 2010-11-10 江苏格林生物科技有限公司 一种α-亚麻酸乙酯配伍小檗碱的减肥物
US8609098B2 (en) * 2010-06-10 2013-12-17 Adbiotech Co., Ltd. Composition for repression of hyperlipidemia and obesity through suppression of intestinal cholesterol absorption
CN101935319A (zh) 2010-09-09 2011-01-05 陕西科技大学 一种黄连素有机酸盐和黄连素有机酸盐包合物及其制备方法
CN102078418B (zh) 2011-01-14 2012-04-18 广东药学院 一种防治脂代谢紊乱的复方中药提取物及其制备方法
CN102225961A (zh) 2011-04-21 2011-10-26 东北林业大学 小檗碱9位偶合胆酸新衍生物及其制备方法
CN102370643A (zh) 2011-07-20 2012-03-14 吉林敖东集团大连药业股份有限公司 盐酸小檗碱药物组合物及其制备方法
ES2769786T3 (es) * 2011-10-14 2020-06-29 Recordati Ag Anticuerpos y métodos para enfermedades relacionadas con la vía Wnt
CN102580087B (zh) 2012-03-08 2013-08-21 董萍 一种可用于人体局部减肥和美体的原位脂肪细胞系复合抑制剂及其制备方法
CN103319479B (zh) * 2012-03-20 2015-08-26 王从品 大黄酸小檗碱离子对化合物、制备方法及应用
US8652518B2 (en) 2012-04-15 2014-02-18 Jahahreeh Finley Compositions and methods for the prevention and treatment of diseases or conditions associated with oxidative stress, inflammation, and metabolic dysregulation
CN102702190B (zh) * 2012-07-02 2016-04-27 东北制药集团股份有限公司 一种小檗碱静电复合物及其制备方法
BR112015004734A2 (pt) * 2012-09-07 2017-11-21 Sanofi Sa proteínas de fusão para tratar uma síndrome metabólica
CA2912302A1 (en) 2013-05-14 2014-11-20 University Of Prince Edward Island Compositions and methods for treating cardiometabolic diseases and disorders
CN103989677A (zh) 2013-12-20 2014-08-20 中国药科大学 去亚甲基小檗碱在制备降血糖药物中的应用
US20150284406A1 (en) * 2014-04-04 2015-10-08 North American Biomedical Research Center Usa, Inc Berberine-ursodeoxycholic acid conjugate for treating the liver
WO2015183794A1 (en) * 2014-05-27 2015-12-03 City Of Hope Tgr5 agonist complexes for treating diabetes and cancer
AU2015296098B2 (en) * 2014-07-29 2019-06-27 Shenzhen Hightide Biopharmaceutical, Ltd. Berberine salts, ursodeoxycholic salts and combinations, methods of preparation and application thereof

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