WO2019120162A1 - Compositions, kits and methods for treating type ii diabetes mellitus - Google Patents

Compositions, kits and methods for treating type ii diabetes mellitus Download PDF

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Publication number
WO2019120162A1
WO2019120162A1 PCT/CN2018/121463 CN2018121463W WO2019120162A1 WO 2019120162 A1 WO2019120162 A1 WO 2019120162A1 CN 2018121463 W CN2018121463 W CN 2018121463W WO 2019120162 A1 WO2019120162 A1 WO 2019120162A1
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WO
WIPO (PCT)
Prior art keywords
inhibitor
blood glucose
biguanide
reduction agent
dpp
Prior art date
Application number
PCT/CN2018/121463
Other languages
English (en)
French (fr)
Inventor
Pei-Ran Wang
Original Assignee
Vitnovo, Inc.
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 Vitnovo, Inc. filed Critical Vitnovo, Inc.
Priority to CN201880080992.XA priority Critical patent/CN111655275B/zh
Priority to AU2018391714A priority patent/AU2018391714A1/en
Publication of WO2019120162A1 publication Critical patent/WO2019120162A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine

Definitions

  • the present method comprises administered to the subject the plant extract of Hedychium coronarium Koenig and a combination of biguanide and SGLT2 inhibitor.
  • the biguanide is metformin
  • theSGLT2 inhibitor is ertugliflozin.
  • FIG 1B is the HPLC spectrums of the HC extract prepared in accordance with Example 1.2 of this invention.
  • Effective amount will vary with such factors as the particular condition being treated, the physical condition of the patient (e.g., the patient's body mass, age, or gender) , the type of mammal or animal being treated, the duration of the treatment, the nature of concurrent therapy (if any) , and the specific formulations employed and the like. Effective amount may be expressed, for example, as the total mass of the active agent (e.g., in grams, milligrams or micrograms) per day, or as the weight of the active agent per Kg of the body weight. The effective amount may be divided into one, two or more doses in a suitable form to be administered at one, two or more times throughout a designated time period.
  • the present plant extract of Hedychium coronarium Koenig is prepared by a method that comprises steps of:
  • the thus produced plant extract of Hedychium coronarium Koenig may be further subject to at least one chromatography (e.g., high performance liquid chromatography (HPLC) ) treatment.
  • HPLC high performance liquid chromatography
  • the plant extract of Hedychium coronarium Koenig is subjected to one run of HPLC treatment.
  • the plant extract of Hedychium coronarium Koenig is subjected to at least two runs of HPLC treatment for further purification.
  • the present plant extract of Hedychium coronarium Koenig is characterized in having a HPLC spectrum substantially as depicted in FIG 1A.
  • the present plant extract of Hedychium coronarium Koenig is characterized in having a HPLC spectrum substantially as depicted in FIG 1B.
  • insulin refers to purified, synthetic and/or biotechnologically derived products that are the same as, or similar to, naturally occurring insulins in structure, use, and intended effect and are of value in the treatment of diabetes mellitus.
  • insulin may be directly recovered from pancreatic tissues of a mammal, such as pancreas glands of farm animals (e.g., pig) .
  • pancreas glands of farm animals e.g., pig
  • insulin may be produced by recombinant technology.
  • Suitable examples of sulfonylurea include, but are not limited to, glibenclamide, gliclazide, glimepiride, and glipizide.
  • TZD examples include, but are not limited to, pioglitazone, rosiglitazone, lobeglitazone, ciglitazone, darglitazone, englitazone, netoglitazone, rivoglitazone, and troglitazone.
  • GLP-1 receptor agonist examples include, but are not limited to, liraglutide, exenatide, albiglutide or LY2189265.
  • the plant extract of Hedychium coronarium Koenig is administered to a subject in need thereof along with a SGLT2 inhibitor (e.g., ertugliflozin) , in which the combined treatment results in synergistically reduction in the levels of blood glucose.
  • a SGLT2 inhibitor e.g., ertugliflozin
  • the plant extract of Hedychium coronarium Koenig is administered to a subject in need thereof along with biguanide (e.g., metformin) and a DDP-4 inhibitor (e.g., sitagliptin) , in which the combined treatment results in synergistically reduction in the levels of blood glucose.
  • biguanide e.g., metformin
  • DDP-4 inhibitor e.g., sitagliptin
  • the plant extract of Hedychium coronarium Koenig and the blood glucose reduction agent may be respectively administered to the subject in need of such treatment in the amount of 0.1 to 2,000 mg/day, such as 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90
  • the plant extract of Hedychium coronarium Koenig and the blood glucose reduction agent are respectively administered in the amount of about 11 mg/Kg and about 3.5 mg/Kg to a human subject.
  • the blood glucose reduction agent is a dipeptidyl peptidase-4 (DPP-4) inhibitor, insulin, an insulin analogue, biguanide, sulfonylurea, thiazolidinedione (TZD) , sodium-glucose co-transporter 2 (SGLT2) inhibitor, ⁇ –glycosidase inhibitor, a glucagon-like peptide 1 (GLP-1) receptor agonist, or a combination thereof.
  • DPP-4 dipeptidyl peptidase-4
  • ZTD thiazolidinedione
  • SGLT2 sodium-glucose co-transporter 2
  • SGLT2 sodium-glucose co-transporter 2
  • GLP-1 glucagon-like peptide 1
  • GLP-1 receptor agonist examples include, but are not limited to, liraglutide, exenatide, albiglutide or LY2189265.
  • the liquid may include a solution, suspension, emulsion, precipitate, or any other desired liquid media carrying the plant extract of Hedychium coronarium Koenig and the blood glucose reduction agent.
  • the liquid may be designed to improve the solubility of the plant extract of Hedychium coronarium Koenig and the blood glucose reduction agent upon release, or may be designed to form a drug-containing emulsion or dispersed phase upon release. Examples of such techniques are well known in the related art.
  • Soft gelatin capsules may be coated, as desired, with a functional coating, such as to delay the release of the drug.
  • the plant extract of Hedychium coronarium Koenig and the blood glucose reduction agent may be formulated into injectable forms for intravenous, subcutaneous or intramuscular administration.
  • An injection can be prepared by dissolving the plant extract of Hedychium coronarium Koenig and the blood glucose reduction agent in water soluble solution such as physiological saline, or water insoluble solution consisting of organic esters such as propylene glycol, polyethylene glycol, or vegetable oils (e.g., sesame oil) .
  • a powdery formulation it may contain water-absorbing materials such as water-soluble polyacrylates, cellulose low-alkyl esters, polyethylene glycol polyvinyl pyrrolidone, amylase and etc, and non-water absorbing materials such as cellulose, starches, gums, vegetable oils or cross-linked polymers. Further, antioxidants, colorants, preservatives may be added to the powdery formulation.
  • the liquid or powdery formulation may be administered by use of a spray apparatus.
  • a further aspect of the present invention relates to a kit for the treatment of type II diabetes mellitus.
  • the kit includes, at least, a first container containing the present plant extract of Hedychium coronarium Koenig; and a second container containing therein a blood glucose reduction agent; and a legend providing instruction to the user on how to administer the plant extract of Hedychium coronarium Koenig and the blood glucose reduction agent for the treatment of type II diabetes.
  • NIDDM Non-insulin dependent diabetic mellitus
  • BKS. Cg-Dock 7 m +/+ Lepr db /JNarl Non-insulin dependent diabetic mellitus male db/db
  • HC extract the extract of the overground part of Hedychium coronarium Koenig
  • Example 1 the effects of the HC extract of Example 1 and/or sitagliptin (i.e., DDP-4 inhibitor) on blood glucose level and glucose tolerance were evaluated by use of NIDDM mice, which were born with mild defects in the insulin signaling cascade that gave rise to insulin resistance and subsequent progression to a diabetic phenotype. The animals were treated by the manner described in the “Material and Methods” section.
  • sitagliptin i.e., DDP-4 inhibitor
  • the HC extract (80 mg/Kg) and sitagliptin (40 mg/Kg) independently resulted in a reduction in the fasting blood glucose level in NIDDM mice; however, what was more surprised was, when the HC extract and sitagliptin were administered together, a synergistic reduction in the fasting blood glucose level was found 30 minutes post glucose treatment, as compared with that of NIDDM mice treated with HC extract alone or sitagliptin alone (FIG 2) .
  • the present HC extract is more effective in facilitating the action of metformin in reducing blood glucose level than that of other known agents, such as DPP-4 inhibitor, and SGLT2 inhibitor.
  • FIG 5 depicts the combined treatments of HC extract (80 mg/Kg) , metformin (150 mg/Kg) , and sitagliptin (40 mg/Kg) on the fasted blood glucose.
  • HC extract alone was slightly more effective than the combination of metformin and sitagliptin in reducing the blood glucose levels on day 29.
  • HC extract alone was slightly more effective than the combination of metformin and sitagliptin in reducing the blood glucose levels on day 29.
  • HC extract alone was slightly more effective than the combination of metformin and sitagliptin in reducing the blood glucose levels on day 29.
  • HC extract alone was slightly more effective than the combination of metformin and sitagliptin in reducing the blood glucose levels on day 29.
  • HC extract alone was slightly more effective than the combination of metformin and sitagliptin in reducing the blood glucose levels on day 29.
  • HC extract alone was slightly more effective than the combination of metformin and sitagliptin in reducing the blood glucose levels on
  • the trial study was carried out in patients aged 20-70 years old diagnosed with Type II diabetes in Taiwan, each receiving the designated treatments. OGTT was performed and blood samples were taken at designated times as set forth in the “Materials and Methods” section.
  • ⁇ Acceptable forms include:
  • Impaired renal function defined as serum-creatinine at least 1.3 mg/dL (at least 115 ⁇ mol/L) for males and at least 1.2 mg/dL (at least 106 ⁇ mol/L) for females

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  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Diabetes (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Botany (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Biotechnology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
PCT/CN2018/121463 2017-12-18 2018-12-17 Compositions, kits and methods for treating type ii diabetes mellitus WO2019120162A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CN201880080992.XA CN111655275B (zh) 2017-12-18 2018-12-17 用以治疗第二型糖尿病的组合物、试剂盒及方法
AU2018391714A AU2018391714A1 (en) 2017-12-18 2018-12-17 Compositions, kits and methods for treating type II diabetes mellitus

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201762599822P 2017-12-18 2017-12-18
US62/599,822 2017-12-18

Publications (1)

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WO2019120162A1 true WO2019120162A1 (en) 2019-06-27

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CN (1) CN111655275B (zh)
AU (1) AU2018391714A1 (zh)
TW (1) TWI756500B (zh)
WO (1) WO2019120162A1 (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021258851A1 (zh) * 2020-06-22 2021-12-30 广州市力鑫药业有限公司 一种治疗糖尿病的药物组合物及其制备方法
WO2023007511A1 (en) * 2021-07-26 2023-02-02 Unison Pharmaceuticals Pvt. Ltd. A pharmaceutical composition comprising combination of sglt2 inhibitor and dpp-iv inhibitor

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2353605A1 (en) * 2010-02-08 2011-08-10 Development Center For Biotechnology Use of overground part of hedychium coronarium koenig in reducing blood glucose; extracts and compositions of overground part of hedychium coronarium koenig and their uses
CN102160889A (zh) * 2010-02-08 2011-08-24 财团法人生物技术开发中心 姜花地上部分的提取物和组合物与其用途
US20130040004A1 (en) * 2011-08-08 2013-02-14 Development Center For Biotechnology Plant extract for treating diabetes and process for making same
TWI387461B (zh) * 2010-02-08 2013-03-01 Dev Center Biotechnology 野薑花（ｈｅｄｙｃｈｉｕｍ ｃｏｒｏｎａｒｉｕｍ ｋｏｅｎｉｇ）地上部份於降低血糖之用途；野薑花地上部份之萃取物及組合物與其用途

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9150482B2 (en) * 2012-06-06 2015-10-06 Development Center For Biotechnology GLP-1 potentiators from hedychium coronarium and their applications
CN104758772A (zh) * 2015-04-03 2015-07-08 周佩龙 一种提高糖耐量的山姜花提取物及其用途

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2353605A1 (en) * 2010-02-08 2011-08-10 Development Center For Biotechnology Use of overground part of hedychium coronarium koenig in reducing blood glucose; extracts and compositions of overground part of hedychium coronarium koenig and their uses
CN102160889A (zh) * 2010-02-08 2011-08-24 财团法人生物技术开发中心 姜花地上部分的提取物和组合物与其用途
TWI387461B (zh) * 2010-02-08 2013-03-01 Dev Center Biotechnology 野薑花（ｈｅｄｙｃｈｉｕｍ ｃｏｒｏｎａｒｉｕｍ ｋｏｅｎｉｇ）地上部份於降低血糖之用途；野薑花地上部份之萃取物及組合物與其用途
US20130040004A1 (en) * 2011-08-08 2013-02-14 Development Center For Biotechnology Plant extract for treating diabetes and process for making same

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
PRABHAKAR P.K. ET AL.: "Combination therapy: A new strategy to manage diabetes and its complications", PHYTOMEDICINE, vol. 21, no. 2, 15 January 2014 (2014-01-15) - 31 December 2014 (2014-12-31), pages 123 - 130, XP055619697 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021258851A1 (zh) * 2020-06-22 2021-12-30 广州市力鑫药业有限公司 一种治疗糖尿病的药物组合物及其制备方法
WO2023007511A1 (en) * 2021-07-26 2023-02-02 Unison Pharmaceuticals Pvt. Ltd. A pharmaceutical composition comprising combination of sglt2 inhibitor and dpp-iv inhibitor

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CN111655275A (zh) 2020-09-11
AU2018391714A1 (en) 2020-07-02
CN111655275B (zh) 2022-05-24
TW201927329A (zh) 2019-07-16
TWI756500B (zh) 2022-03-01

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