WO2015032011A1 - 含有亚铁氨基酸螯合物的组合物在制备抗癌症的药物中的用途 - Google Patents
含有亚铁氨基酸螯合物的组合物在制备抗癌症的药物中的用途 Download PDFInfo
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- WO2015032011A1 WO2015032011A1 PCT/CN2013/001043 CN2013001043W WO2015032011A1 WO 2015032011 A1 WO2015032011 A1 WO 2015032011A1 CN 2013001043 W CN2013001043 W CN 2013001043W WO 2015032011 A1 WO2015032011 A1 WO 2015032011A1
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- cancer
- amino acid
- ferrous
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- acid chelate
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- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
- A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
-
- 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
- A61K31/28—Compounds containing heavy metals
- A61K31/295—Iron group metal compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
Definitions
- composition containing a ferrous amino acid chelate compound for preparing an anticancer drug
- the present invention relates to the use of a composition comprising a ferrous amino acid chelate, and to the use of the composition in the manufacture of a medicament for the fight against cancer. Background technique
- Cancer or malignant tumor is one of the leading causes of death in the world's population.
- the cancer death rate is ranked mainly for lung cancer, stomach cancer, liver cancer, colorectal cancer, breast cancer and cervical cancer. According to the statistics of the World Health Organization, nearly 20 years The lung cancer mortality rate is the fastest.
- the lung cancer is divided into small cell lung cancer and non-small cell lung carcinoma (NSCLC) according to its cell characteristics and clinical manifestations.
- Small cell lung cancer occurs mostly in men and is closely related to smoking, accounting for 25% of all lung cancer patients; and small cells grow fast and easily spread from lymph or blood to other organs.
- Non-small cell carcinoma accounts for 75% of all lung cancer patients. Common include: squamous cell carcinoma, adenocarcinoma, large cell carcinoma.
- Squamous cell carcinoma also known as epidermoid carcinoma
- epidermoid carcinoma is common in male smokers. It is mostly localized outward extension in the early stage and spreads through the bloodstream in the later stage.
- Adenocarcinoma is the most common type of lung cancer, often after distant metastasis. Clinical symptoms appear, and lung cancer is often the case in non-smokers; large cell carcinoma, which grows slowly, but also spreads through the blood and lymph.
- Small cell lung cancer is quite sensitive to chemical and radiation therapy, but after treatment, most cases will recur and develop drug resistance within two years. Although non-small cell lung cancer grows slowly, only about four minutes can be treated with early surgery. One, and most of them are not sensitive to chemical drugs and radiation therapy; for the above reasons, lung cancer patients are generally less and better.
- liver cancer is the top ten cancers. Apart from surgical resection, it is not only treated by chemotherapy or radiation therapy, but the above treatments often cause unbearable pain and side effects, so the prior art is Targeted therapeutic drugs are used for anti-hepatocarcinoma treatment, and therapeutic purposes are aimed at inhibiting the pathway of mutation, proliferation or proliferation involved in the progression of liver cancer cells, inhibiting angiogenesis of liver cancer cells or promoting the death of liver cancer cells or preventing the spread of cancer cells. Since there is no obvious symptom in the early stage of liver cancer, prevention has become more and more important.
- compositions containing a ferrous amino acid chelate compound for use in the preparation of a medicament for combating cancer which comprises ferrous metal sequestration
- the composition of the composition has an anticancer effect.
- the present invention provides a use of a composition comprising a ferrous amino acid chelate compound for the preparation of a medicament for preventing cancer, wherein the medicament comprises a composition effective for anticancer dose comprising a ferrous amino acid chelate compound and A pharmaceutically acceptable carrier.
- the "composition containing a ferrous amino acid chelate” is a composition containing a ferrous amino acid chelate prepared by mixing inorganic iron with an amino acid; preferably, The inorganic iron includes, but is not limited to, ferrous sulfate, ferrous chloride, and ferrous pyrophosphate; preferably, the amino acid is glycine.
- the composition containing the ferrous amino acid chelate compound contains 95% by weight to 100% ferrous glycine acid chelate; more preferably, 98% to 99.9% by weight of ferrous glycine chelate.
- the composition of the ferrous amino acid chelate is obtained by heating ferrous sulfate and glycine at 60 ° C to 90 ° C for 8 hours to 48 hours, wherein the ferrous sulfate The weight ratio to glycine is between 1: 1.2 and 1: 1.5.
- the ferrous metal amino acid chelate-containing composition comprises at least one ferrous amino acid chelate compound, and the ferrous metal chelate compound has a chelating ratio of ferrous to amino acid of 1:1 to 1 Between: 4; more preferably, the ratio of ferrous and amino acid chelating of the ferrous amino acid chelate is between 1:1.5 and 1:2.5.
- the composition containing the ferrous amino acid chelate compound comprises a reducing agent which maintains the oxidation state of the ferrous iron of the composition containing the ferrous amino acid chelate compound, and also enhances the ferrous iron content.
- the composition of the amino acid chelate is in the intestinal absorption rate of the receptor, wherein the reducing agent includes, but is not limited to, ascorbic acid, citric acid, acetic acid, propionic acid. ), butyric acid, lactic acid, 3 ⁇ 4: malic acid, sulfonic acid, and succinic acid.
- anti-cancer means an effective inhibition or soothing of cancer
- effective dose means an amount effective to achieve a desired or inhibited cancer result at a dose and for a desired period of time; It means that the growth of lung cancer or liver cancer tumor can be slowed down, stopped, and even killed.
- the dose for effectively inhibiting or relieving lung cancer or liver cancer tumor can be administered by administering a specific range of ferrous metal-containing chelate The composition of the composition is obtained by measuring the change in tumor volume over a specific time frame.
- pharmaceutically acceptable carrier includes any and all solvents, dispersion media, clothing, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, which are physiologically compatible.
- pharmaceutically acceptable carriers include one or more of water, saline, phosphate buffered saline, dextrose, glycerol, ethanol, and the like, and combinations thereof.
- preferred compositions include isotonic agents, such as sugars, mannitol, sorbitol polyols or sodium chloride.
- the pharmaceutically acceptable carrier may further comprise minor amounts of auxiliary substances such as wetting or emulsifying agents, preservatives or buffers.
- the effective dose of the composition containing the ferrous amino acid chelate is between 0.2 mg/kg/day (mg/kg/day) and 15 mg/kg/day; more preferably, 0.3 mg/kg/day to 14 mg/kg/day; preferably, 0.4 mg/kg/day to 12 mg/kg/day.
- the medicaments of the invention may exist in a variety of forms. Such forms include, but are not limited to, liquid, semi-solid, and solid pharmaceutical forms such as liquid solutions (e.g., injectable and infusible solutions), dispersions or suspensions, lozenges, pills, powders, liposomes, and suppositories.
- liquid solutions e.g., injectable and infusible solutions
- dispersions or suspensions lozenges
- pills pills, powders, liposomes, and suppositories.
- the preferred form depends on the intended mode of administration and therapeutic application;
- the medicament of the present invention is in the form of an orally or infusible solution, and the preferred mode of administration is enteral mode, such as oral administration.
- the medicament comprising a composition effective for anti-cancer dose containing a ferrous amino acid chelate is administered orally.
- the medicament further comprises an excipient to render the medicament suitable for enteral or parenteral dosage forms.
- the enteral dosage form is an oral dosage form including, but not limited to, solutions, suspensions, conjugates, and capsules.
- the cancer includes, but is not limited to, melanoma.
- the cancer includes, but is not limited to, a brain tumor, a low-grade astrocytoma, a high-grade astrocytoma, a pituitary adenoma ( Pituitary adenoma), meningioma, central nervous lymphoma (CNS lymphoma) oligodendroglioma, craniopharyngioma, ependymoma glial cell Brain stem tumor, head and neck tumor, laryngeal cancer, mouth.
- a brain tumor a low-grade astrocytoma
- a high-grade astrocytoma a pituitary adenoma
- Pituitary adenoma pituitary adenoma
- meningioma oligodendroglioma
- craniopharyngioma ependymoma glial cell Brain stem tumor, head and neck tumor, laryngeal cancer, mouth.
- ⁇ Yue-like carcinoma thyroid cancer
- oral cancer oral cavity tumor
- thoracic tumor chest wall tumors
- small cell lung cancer non-small cell lung cancer (NSCLC) > thymoma, mediastinal tumor, male breast cancer (male Breast cancer), abdomen-pelvis tumor, hepatoma, liver adenocarcinoma, gallbladder cancer, biliary tract cancer, pancreatic Cancer), small intestinal tumor, large intestinal tumor, anal cancer, bladder cancer, renal cell carcinoma, cervical cancer (cervix cancer), endometrial cancer, ovarian cancer, uterine sarcoma, and skin cancer.
- the cancer is liver cancer or lung cancer.
- the composition containing the ferrous amino acid chelate compound according to the present invention can be passed through the stomach while maintaining a chelated state with the ferrous iron due to the small molecular weight of the amino acid, and is subjected to the composition containing the ferrous amino acid chelate compound by the present invention. Does not affect the body weight change of the receptor; in addition, in the present invention, a composition containing a ferrous amino acid chelate is compared
- the application of the commercially available amino acid ferrous iron and inorganic iron (such as ferrous sulfate) has the effect of inhibiting or relieving lung cancer or liver cancer tumor, and therefore, the composition of the ferrous metal chelate-containing composition of the present invention may be used. Used to suppress or soothe cancer, especially lung cancer or liver cancer.
- Fig. 1 is a graph showing changes in lung cancer tumor volume of a lung cancer tumor cell after administration of a composition containing a ferrous amino acid chelate compound in a rat (BALB/c nu/nu mice) for 1 week;
- Figure 2 is a bar graph of body weight change after administration of a composition containing a ferrous amino acid chelate compound to rats for 6 weeks
- Figure 3 is a Severe Combined Immunodeficiency Mice (SCID mice) (hereinafter noted as SCID mouse) a curve of fold change in liver cancer tumor volume of a liver cancer tumor cell after administration of a composition containing a ferrous amino acid chelate for 1 week;
- SCID mice Severe Combined Immunodeficiency Mice
- Figure 4 is a graph showing the survival rate of SCID mice injected with liver cancer tumor cells within 5 weeks;
- Fig. 5 shows the rats divided into five groups, wherein the control group is administered with a phosphate solution, and A is a composition containing a ferrous amino acid chelate compound at a dose of 1.2 mg/kg/day, respectively, containing a ferrous amino acid chelate compound. a composition, 12 mg/kg/day of a composition containing a ferrous amino acid chelate; B is an amino acid ferrous (Ferrochel®) at a dose of
- the tumor volume changes of lung cancer tumor cells were injected into the lung cancer cells after 7 days in each group.
- Figure 6 shows the rats divided into five groups, wherein the control group is administered with a citrate solution, and A is a composition containing a ferrous amino acid chelate, at a dose of 4 mg/kg/day, respectively, containing ferrous amino acid chelate.
- A is a composition containing a ferrous amino acid chelate, at a dose of 4 mg/kg/day, respectively, containing ferrous amino acid chelate.
- B is an amino acid ferrous (Ferrochel®) at a dose of 4 mg/kg/day
- C ferrous sulfate at a dose of The dose is 4 mg/kg/day.
- Each group was given a rat
- a composition containing a ferrous amino acid chelate of the present invention is used against cancer, wherein the composition containing a ferrous amino acid chelate is mixed with its pharmaceutically acceptable carrier as an inhibitor or treatment Cancer drugs.
- composition containing a ferrous amino acid chelate is mixed with inorganic iron and amino acid and heated A composition containing a ferrous amino acid chelate prepared at one time.
- the composition containing a ferrous amino acid chelate compound includes a reducing agent; wherein the reducing agent is ascorbic acid, citric acid, acetic acid, propionic acid, butyric acid, lactic acid, hydroxysuccinic acid, Sulfonic acid or succinic acid.
- the reducing agent is ascorbic acid, citric acid, acetic acid, propionic acid, butyric acid, lactic acid, hydroxysuccinic acid, Sulfonic acid or succinic acid.
- the amino acid is glycine, thereby forming a combination containing a ferrous glycoside chelate And have been shown to have the effect of inhibiting cancer cell cells.
- This example is a composition for preparing a ferrous metal chelating composition which is prepared in the following manner.
- the ferrous sulfate and the glycine are mixed at a weight ratio of 1:1.3 and heated at 60 ° C to 90 ° C for 8 hours to 48 hours to obtain the composition containing the ferrous amino acid chelate, wherein the ferrous iron
- the ratio of the ferrous iron to the amino acid chelate of the amino acid chelate is between 1:1 and 1:4; and the obtained composition containing the ferrous amino acid chelate is prepared to a concentration of 0.1 ⁇ / ⁇ , ie, per 100 A microliter containing 10 micrograms), 0.3 ⁇ ⁇ / ⁇ 1, 1 ⁇ ⁇ / ⁇ 1 and 3 compositions.
- the lung cancer cell line ( ⁇ 549) was contained with 10% fetal bovine serum (FBS), 1% penicillin (100 U/mL)-streptomycin (100 g/mL) (penicillin-streptomycin) and 1% glutamine.
- FBS fetal bovine serum
- penicillin 100 U/mL
- penicillin-streptomycin 100 g/mL
- glutamine 200 mM
- Dulbecco's Modified Eagle's medium (DMEM) was cultured in a 37 ° C, 5% carbon dioxide incubator until the cells were attached at 7 to 8 minutes. Subculture is carried out.
- Wipe liver cancer cells (SK Hepl) with Du's modified Inge with 10% fetal bovine serum (FBS), 1% non-essential amino acid (NEAA) and 1% penicillin-streptomycin Dulbecco's Modified Eagle's medium (DMEM) was cultured in a 37 ° C, 5% carbon dioxide incubator and subcultured for about 3 days to 4 days.
- FBS fetal bovine serum
- NEAA non-essential amino acid
- DMEM penicillin-streptomycin Dulbecco's Modified Eagle's medium
- Preparation Example 1 was prepared at a concentration of 0.1 ⁇ ⁇ / ⁇ 0.3 ⁇ ⁇ / amino acid composition comprising iron chelate ⁇ 1 ⁇ ⁇ / ⁇ 1 respectively at a dose of 0.4 mg / kg / day, 1.2 mg / Feeding rats (B ALB/c nu/nu mice) at kg/day or 4 mg/kg/day [purchased from National Laboratory Animal Center (Taipei, Taiwan), approximately 5 weeks to 6 weeks of age], and sterile Water as a control group, after applying ferrous amino acid chelate or sterile water for 7 days, the above
- the resulting culture prepared in Example 2 1 10 7 cell / mL of mouse lung cancer cells were injected into hind trees brachial artery near the subcutaneous tissue, after every 7 days vernier valve and foot volume measuring tumor size, and mice were sacrificed after 6 weeks.
- the formula for calculating the tumor volume is as follows:
- the tumor volume is (a X b 2 )/2 and the unit is mm cubic (mm 3 ).
- the lung cancer tumor volume increased with the number of days, but the composition containing the ferrous amino acid chelate at a dose of 1.2 mg/kg/day or 4 mg/kg/day has a better inhibition of lung cancer tumor volume. Effect. Further, as shown in Fig. 2, the composition containing the ferrous amino acid chelate compound at the aforementioned concentration did not inhibit the normal growth of the rat.
- the 4 mg/kg/day ferrous amino acid chelate was administered to SCID mice (purchased from the Animal Center of Taiwan University Medical College) 5 times a week (about 6 weeks old), and the sterile water was used as a control group.
- SCID mice purchased from the Animal Center of Taiwan University Medical College
- 10 7 cells/mL of liver cancer cells (100 ⁇ M) obtained in the above Preparation Example 3 were injected into the subcutaneous tissue near the lower back of SCID mice. Tumor size and volume were measured with a vernier valve rule every 7 days and sacrificed after 4 weeks.
- the tumor volume of liver cancer increased with the number of weeks, and at week 4, the volume of liver cancer tumors in SCID mice of the control group increased 3.5 times, but the concentration of administration was 4 mg/kg/day.
- the volume of the liver cancer tumor of the SCID mouse containing the composition of the ferrous amino acid chelate compound is only increased by 1.8 times as much as the original, and accordingly, the composition containing the ferrous amino acid chelate compound described in the present invention has the tumor volume inhibiting the liver cancer. effect.
- the survival rate of the SCID mice of the control group was 75%, but the administration concentration was 4 mg/
- the viability of the ferrous/day ferrous metal chelate-containing composition was 100%, thus indicating that administration of a composition containing a ferrous amino acid chelate can increase the survival rate of SCID mice.
- the rats were divided into 5 groups, and the first group was given phosphate buffered saline.
- PBS PBS
- the composition of the fourth group was administered at a dose of 1.2 mg/kg/day of ferrous iron (Ferrochel®) (purchased from Albion, USA), and the fifth group was administered at a dose of 1.2 mg/kg/day of ferrous ferrous ( After 7 days, the 1 ⁇ 10 7 cell/mL lung cancer cells (100 ⁇ 1 ) obtained in the above Preparation Example 2 were injected into the subcutaneous tissue near the hind leg artery ankle, and then traveled every 7 days. The size and volume of the tumor were measured with a standard valve rule, and the mice were sacrificed after 6 weeks.
- the dose of 12 mg/kg/day or 1.2 mg/kg/day of the composition containing ferrous amino acid chelate (group A) was 5 weeks later.
- the composition containing the ferrous amino acid chelate compound has an effect of suppressing the tumor volume of the lung cancer as compared with the amino acid ferrous iron (Ferrochel®) (group B), ferrous sulfate, and the control group.
- the rats were divided into 5 groups, the first group was given buffered physiological saline as the control group, the second group was administered with the dose of 4 mg/kg/day of the composition containing the ferrous amino acid chelate, and the third group was applied.
- the 10 7 cell/mL liver cancer fine color (100 ⁇ l injection) obtained in the above Preparation Example 2 was injected into the subcutaneous tissue near the lower back of the rat, and then every 7 days. Tumor size and volume were measured with a vernier valve ruler and sacrificed after 5 weeks.
- a composition containing a ferrous amino acid chelate compound (group A) at a dose of 4 mg/kg/day or 12 mg/kg/day, after 5 weeks, contains a combination of ferrous amino acid chelate Compared with the amino acid ferrous iron (Ferrochel®) (group B), ferrous sulfate (group C) and the control group, the substance has an effect of suppressing the tumor volume of liver cancer.
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA2898771A CA2898771C (en) | 2013-09-05 | 2013-09-05 | Use of composition containing ferrous amino acid chelate in preparation of anti-cancer medicament |
AU2013400082A AU2013400082B2 (en) | 2013-09-05 | 2013-09-05 | Use of composition containing ferrous amino acid chelate in preparation of anti-cancer medicament |
CN201380071525.8A CN104955452B (zh) | 2013-09-05 | 2013-09-05 | 含有亚铁氨基酸螯合物的组合物在制备抗癌症的药物中的用途 |
PCT/CN2013/001043 WO2015032011A1 (zh) | 2013-09-05 | 2013-09-05 | 含有亚铁氨基酸螯合物的组合物在制备抗癌症的药物中的用途 |
EP13893164.7A EP3042652B1 (en) | 2013-09-05 | 2013-09-05 | Use of composition containing ferrous amino acid chelate in preparation of anti-cancer medicament |
JP2015559400A JP5973684B2 (ja) | 2013-09-05 | 2013-09-05 | 癌治療のための使用 |
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PCT/CN2013/001043 WO2015032011A1 (zh) | 2013-09-05 | 2013-09-05 | 含有亚铁氨基酸螯合物的组合物在制备抗癌症的药物中的用途 |
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WO2015032011A1 true WO2015032011A1 (zh) | 2015-03-12 |
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PCT/CN2013/001043 WO2015032011A1 (zh) | 2013-09-05 | 2013-09-05 | 含有亚铁氨基酸螯合物的组合物在制备抗癌症的药物中的用途 |
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EP (1) | EP3042652B1 (zh) |
JP (1) | JP5973684B2 (zh) |
CN (1) | CN104955452B (zh) |
AU (1) | AU2013400082B2 (zh) |
CA (1) | CA2898771C (zh) |
WO (1) | WO2015032011A1 (zh) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI645848B (zh) * | 2016-12-02 | 2019-01-01 | 普惠德生技股份有限公司 | Use of a composition containing a ferrous amino acid chelate compound for the manufacture of a medicament for preventing cancer metastasis |
WO2019127295A1 (zh) * | 2017-12-29 | 2019-07-04 | 普惠德生技股份有限公司 | 含有亚铁氨基酸螯合物的组合物用于制造抑制血管新生的医药品的用途 |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA3023964A1 (en) * | 2016-05-26 | 2017-11-30 | Profeat Biotechnology Co., Ltd. | Use of composition comprising ferrous amino acid chelate for manufacture of medicine for reducing lactic acid |
CN110198709A (zh) * | 2017-02-17 | 2019-09-03 | 普惠德生技股份有限公司 | 含有亚铁氨基酸螯合物的组合物用于制造治疗肝功能异常的医药品的用途 |
TWI732164B (zh) * | 2018-03-06 | 2021-07-01 | 普惠德生技股份有限公司 | 經燒結的胺基酸亞鐵粒子及其抗病毒的用途 |
TWI710370B (zh) * | 2018-12-20 | 2020-11-21 | 普惠德生技股份有限公司 | 含有亞鐵胺基酸螯合物粒子的組合物用於製備治療或減緩阿茲海默症或帕金森氏症的醫藥品的用途 |
TWI695719B (zh) * | 2018-12-20 | 2020-06-11 | 普惠德生技股份有限公司 | 含有亞鐵胺基酸粒子的組合物及其用於製造治療或改善胰臟相關疾病的醫藥品的用途 |
JP6998087B2 (ja) * | 2018-12-20 | 2022-02-04 | 普惠徳生技股▲ふん▼有限公司 | 第一鉄アミノ酸粒子を含む組成物、およびその組成物を含む、膵臓関連疾患の治療または改善のための薬剤 |
CN112168843A (zh) * | 2019-07-05 | 2021-01-05 | 普惠德生技股份有限公司 | 经烧结的纳米粒子及其抗病毒的用途 |
US20230012448A1 (en) * | 2021-06-30 | 2023-01-12 | Getwing Biotechnology Medical Co., Ltd | Methods for alleviating kidney disease and fibrosis of organ |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101102762A (zh) * | 2004-12-22 | 2008-01-09 | 药物技术公司 | 含铁组合物 |
EP2306187A1 (en) | 2001-11-13 | 2011-04-06 | Signe BioPharma Inc. | Cancer eradication program |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2041M (fr) * | 1962-04-17 | 1963-09-30 | Andre Anselme Marie | Composition thérapeutique a propriétés cytotoxiques a base d'acide ascorbique et d'ions métalliques. |
US5578637A (en) * | 1995-05-03 | 1996-11-26 | University Of Washington | Methods of inhibition or killing cancer cells using an endoperoxide |
EP1658844A1 (en) * | 2004-10-19 | 2006-05-24 | Gerold Schuler | Use of artemisinin derivatives in the manufacture of a medicament for the treatment of melanoma |
US20090035385A1 (en) * | 2004-12-22 | 2009-02-05 | Drugtech Corporation | Compositions including iron |
AU2007300532A1 (en) * | 2006-09-28 | 2008-04-03 | Merck Sharp & Dohme Corp. | Pharmaceutical compositions of HDAC inhibitors and chelatable metal compounds, and metal-HDAC inhibitor chelate complexes |
JP5611548B2 (ja) * | 2009-07-08 | 2014-10-22 | Sbiファーマ株式会社 | 5−アミノレブリン酸若しくはその誘導体、又はそれらの塩を有効成分とするがんの予防・改善剤 |
-
2013
- 2013-09-05 EP EP13893164.7A patent/EP3042652B1/en not_active Not-in-force
- 2013-09-05 CA CA2898771A patent/CA2898771C/en not_active Expired - Fee Related
- 2013-09-05 WO PCT/CN2013/001043 patent/WO2015032011A1/zh active Application Filing
- 2013-09-05 AU AU2013400082A patent/AU2013400082B2/en not_active Ceased
- 2013-09-05 JP JP2015559400A patent/JP5973684B2/ja not_active Expired - Fee Related
- 2013-09-05 CN CN201380071525.8A patent/CN104955452B/zh not_active Expired - Fee Related
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2306187A1 (en) | 2001-11-13 | 2011-04-06 | Signe BioPharma Inc. | Cancer eradication program |
CN101102762A (zh) * | 2004-12-22 | 2008-01-09 | 药物技术公司 | 含铁组合物 |
Non-Patent Citations (4)
Title |
---|
GREEN E, CLIN CANCER RES, vol. 7, 2001, pages 3574 - 3579 |
KATO ET AL., INT. J. CANCER, vol. 80, 1999, pages 693 - 698 |
SIMONART ET AL., GYNECOLOGIC ONCOLOGY, vol. 85, 2002, pages 95 - 102 |
SINGH ET AL., LIFE SCIENCE, vol. 70, 2001, pages 49 - 56 |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI645848B (zh) * | 2016-12-02 | 2019-01-01 | 普惠德生技股份有限公司 | Use of a composition containing a ferrous amino acid chelate compound for the manufacture of a medicament for preventing cancer metastasis |
WO2019127295A1 (zh) * | 2017-12-29 | 2019-07-04 | 普惠德生技股份有限公司 | 含有亚铁氨基酸螯合物的组合物用于制造抑制血管新生的医药品的用途 |
CN111565728A (zh) * | 2017-12-29 | 2020-08-21 | 普惠德生技股份有限公司 | 含有亚铁氨基酸螯合物的组合物用于制造抑制血管新生的医药品的用途 |
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Publication number | Publication date |
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CN104955452B (zh) | 2017-06-09 |
CA2898771A1 (en) | 2015-03-12 |
CN104955452A (zh) | 2015-09-30 |
EP3042652A1 (en) | 2016-07-13 |
JP2016510006A (ja) | 2016-04-04 |
AU2013400082A1 (en) | 2015-08-06 |
EP3042652B1 (en) | 2018-08-29 |
JP5973684B2 (ja) | 2016-08-23 |
AU2013400082B2 (en) | 2016-01-28 |
CA2898771C (en) | 2017-01-03 |
EP3042652A4 (en) | 2017-04-12 |
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