WO2023109747A1 - Utilisation d'acide 2,4-dihydroxybenzoïque dans un médicament pour le traitement de maladies liées à une surcharge en fer - Google Patents

Utilisation d'acide 2,4-dihydroxybenzoïque dans un médicament pour le traitement de maladies liées à une surcharge en fer Download PDF

Info

Publication number
WO2023109747A1
WO2023109747A1 PCT/CN2022/138376 CN2022138376W WO2023109747A1 WO 2023109747 A1 WO2023109747 A1 WO 2023109747A1 CN 2022138376 W CN2022138376 W CN 2022138376W WO 2023109747 A1 WO2023109747 A1 WO 2023109747A1
Authority
WO
WIPO (PCT)
Prior art keywords
iron overload
iron
dihydroxybenzoic acid
disease
diseases
Prior art date
Application number
PCT/CN2022/138376
Other languages
English (en)
Chinese (zh)
Inventor
张建国
李成
任武贤
韩应兵
堐榜琴
Original Assignee
好啦好了(山西)科技有限公司
张建国
李成
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 好啦好了(山西)科技有限公司, 张建国, 李成 filed Critical 好啦好了(山西)科技有限公司
Publication of WO2023109747A1 publication Critical patent/WO2023109747A1/fr

Links

Images

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
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • 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
    • A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis

Definitions

  • the invention belongs to the field of iron-lowering medicines, and in particular relates to the application of 2,4-dihydroxybenzoic acid or its salt compounds in medicines for treating iron overload diseases.
  • Iron overload includes two aspects: one is exogenous iron overload, and the other is endogenous iron overload.
  • Exogenous iron overload mainly refers to the iron overload caused by long-term dependence on blood transfusion to maintain life, such as: thalassemia, myelodysplastic syndrome, bone marrow aplastic anemia, hemochromatosis, etc., which is blank in China. There is still no corresponding treatment drug.
  • Endogenous iron overload is also called natural iron overload. It is an inevitable result of increasing age and improving living standards. Iron has no obvious excretion mechanism in the human body. As we grow older, there will be more and more iron in the cells, which has become an important factor that endangers human health.
  • diseases related to iron overload covering almost all common human diseases and chronic diseases, such as: diabetes, hypertension, hyperlipidemia, hyperuricemia, coronary heart disease, stroke, vascular sclerosis, liver cirrhosis, pulmonary fibrosis , rheumatoid arthritis, osteoporosis, Alzheimer's disease, tumors, aging, etc.
  • iron overload cannot be treated with iron removal; iron removal cannot replace drug treatment. Its purpose is to make the original therapeutic drugs and Methods to obtain the maximum clinical efficacy.
  • the only clinical first-line iron-removing drug is deferaros, and it is only suitable for exogenous iron overload, that is, iron overload formed after blood transfusion.
  • the serum ferritin value exceeds 1000 ⁇ g/L.
  • iron chelating agents are needed, but the main working principle of iron chelating agents is to compete with serum ferritin for iron.
  • serum ferritin When serum ferritin When the value is lower than 1000 ⁇ g/L, the advantage of competing for iron will decrease, which is manifested clinically in that the speed of iron removal is very slow, and even the goal of effective iron removal cannot be achieved.
  • the iron overload of common diseases and chronic diseases belongs to endogenous iron overload.
  • the serum ferritin value is between 200 and 600 ⁇ g/L. In this area, it is difficult for Delarose to play a role.
  • the iron in serum ferritin has no activity, it will not cause any damage to the cells, on the contrary it is an antioxidant, so why must eliminate the iron in serum ferritin? What we want to eliminate is iron that can cause lipid peroxidation in cells. This iron can only be free iron ions in cells, not iron in serum ferritin. Targeting serum ferritin removal is itself The research and development of iron-removing drugs deviated from the direction.
  • iron complexes such as citric acid, ATP, DTP, GTP and phospholipids.
  • This part belongs to low molecular weight non-protein complex iron and has the properties of free iron. , can catalyze the Haber- Stamms reaction, also known as fluid free iron, this part of iron plays a vital role in the growth, development and metabolism of cells. At the same time, it is most closely related to diseases, and it is the initial substance that triggers free radical reactions.
  • the purpose of removing iron is to reduce this part of iron, which forms a balance relationship with ferritin in cells. It reduces, and iron in cells The protein is reduced, and the serum ferritin is naturally reduced.
  • the present invention provides a compound with a small molecular weight - 2,4-dihydroxybenzoic acid or its salt compound used in medicines for treating iron overload diseases.
  • One aspect of the present invention provides the application of 2,4-dihydroxybenzoic acid or its salt compounds in the preparation of medicines for treating iron overload diseases.
  • the iron overload includes: exogenous iron overload and endogenous iron overload.
  • the exogenous iron overload refers to iron overload caused by long-term dependence on blood transfusion
  • the exogenous iron overload-related diseases are selected from thalassemia, myelodysplastic syndrome, bone marrow Aplastic anemia or hemochromatosis
  • the endogenous iron overload-related diseases are selected from diabetes, hypertension, hyperlipidemia, hyperuricemia, coronary heart disease, stroke, vascular sclerosis, liver cirrhosis, pulmonary fibrosis, rheumatoid arthritis , osteoporosis, Alzheimer's disease, tumors or aging.
  • the exogenous iron overload refers to iron overload caused by myelodysplastic syndrome or bone marrow aplasia anemia.
  • the endogenous iron overload-related diseases are tumors.
  • the endogenous iron overload-related disease is hyperuricemia.
  • the medicine for treating iron overload disease may be in the form of a preparation, and the preparation form is selected from one of oral liquid, injection, tablet, granule, capsule or other dosage forms.
  • the 2,4-dihydroxybenzoic acid in the medicine for treating iron overload disease is administered at a daily dose of 2-6 g, preferably at a daily dose of 3 g.
  • the 2,4-dihydroxybenzoic acid or its salt compound can be taken three times a day, 1-2g each time, and the dosage can be reduced based on body weight.
  • the present invention also provides a pharmaceutical composition for treating iron overload disease in a single dose form, the pharmaceutical composition comprising 2,4-dihydroxybenzoic acid or its salt compound, the single dose form comprising 2,4- 1-2g of 2,4-dihydroxybenzoic acid or its salt compounds in terms of dihydroxybenzoic acid.
  • the single dosage form contains 1 g of 2,4-dihydroxybenzoic acid or its salt compounds in terms of 2,4-dihydroxybenzoic acid.
  • the invention provides the application of the pharmaceutical composition in the treatment of iron overload diseases;
  • the iron overload includes exogenous iron overload and endogenous iron overload;
  • the exogenous iron overload refers to the disease caused by long-term dependence on blood transfusion iron overload,
  • the exogenous iron overload-related diseases are selected from thalassemia, myelodysplastic syndrome, bone marrow aplasia anemia or hemochromatosis;
  • the endogenous iron overload-related diseases are selected from diabetes, hypertension, Hyperlipidemia, high uric acid, coronary heart disease, stroke, vascular sclerosis, liver cirrhosis, pulmonary fibrosis, rheumatoid arthritis, osteoporosis, Alzheimer's disease, tumor or aging.
  • the invention provides the pharmaceutical composition for treating thalassemia, myelodysplastic syndrome, bone marrow aplasia anemia, hemochromatosis, diabetes, hypertension, hyperlipidemia, hyperuric acid, coronary heart disease, stroke, arteriosclerosis , liver cirrhosis, pulmonary fibrosis, rheumatoid arthritis, osteoporosis, Alzheimer's disease, tumors, or aging.
  • said thalassemia, myelodysplastic syndrome, myelodysplastic anemia and hemochromatosis are caused by exogenous iron overload, for example, thalassemia caused by iron overload caused by long-term dependence on blood transfusion , myelodysplastic syndrome, bone marrow aplasia anemia and hemochromatosis; said diabetes, hypertension, hyperlipidemia, hyperuricemia, coronary heart disease, stroke, vascular sclerosis, liver cirrhosis, pulmonary fibrosis, rheumatoid arthritis, Osteoporosis, Alzheimer's disease, tumors and aging are caused by endogenous iron overload.
  • exogenous iron overload for example, thalassemia caused by iron overload caused by long-term dependence on blood transfusion , myelodysplastic syndrome, bone marrow aplasia anemia and hemochromatosis
  • the inventor refined iron removal into three conditions, that is, not only can it enter the cell, but also the ability to complex iron is smaller than that of "ferritin", and at the same time, the ability to complex iron is lower than that of "non-protein protein” in the cell. Iron complexation is large, and only by meeting these three conditions can the purpose of iron removal be achieved quickly, accurately and with little side effects.
  • the essence of the treatment of iron overload is to enter the cell to reduce the ferric iron in the "non-protein complex iron", and then achieve the purpose of reducing the "free iron in the cell".
  • 2,4-dihydroxybenzoic acid of the present invention meets three conditions of iron removal:
  • 2,4-dihydroxybenzoic acid complexed with iron can be detected in urine of mice taking 2,4-dihydroxybenzoic acid, indicating that complexed iron can be excreted from urine; and this compound is Iron reagent, without toxic side effects, is listed as a food additive or spice in the United States and Europe.
  • the present invention directly takes 2,4-dihydroxybenzoic acid or its salt compounds to achieve the purpose of directly reducing "free iron” in non-protein complex iron in cells, and then quickly removes excess iron in the body.
  • 2,4-dihydroxybenzoic acid or its salt compounds have significant iron-lowering effects on serum ferritin, serum iron, liver, kidney, spleen, heart and other tissues, and have short onset time, fast iron-lowering speed,
  • the invention has the obvious advantages of large iron range, good clinical effect and high safety, so it can be used to prepare medicines for treating iron overload diseases.
  • Fig. 1 is the figure of serum ferritin content
  • Figure 2 is a diagram of serum iron concentration
  • Figure 3 is a map of liver iron content
  • Figure 4 is a diagram of iron content in the kidney
  • Figure 5 is a map of iron content in the spleen
  • Figure 6 is a map of heart iron content.
  • Embodiment 1 The animal iron removal experiment is as follows:
  • Modeling reagent iron dextran, production unit: Aladdin, iron content 35-40% (W/W).
  • Gender half male and half male
  • the configuration of the compound 2,4-dihydroxybenzoic acid accurately weigh the powder of 2,4-dihydroxybenzoic acid, dissolve it in 0.5% normal saline containing methylcellulose in a sterile environment of a biological safety cabinet, and grind it thoroughly After dissolving, administer (preparation as it is used now).
  • deferarose accurately weigh deferarose powder, dissolve in 0.5% physiological saline containing methylcellulose in the aseptic environment of the biological safety cabinet, after grinding and fully dissolving, administer ).
  • Preparation of iron dextran Precisely weigh iron dextran powder, dissolve it in physiological saline for injection in a sterile environment of a biological safety cabinet, and administer it after it is fully dissolved (preparation for current use).
  • the model group was intraperitoneally injected with 250 mg/kg of iron dextran (concentration: 25 mg/mL), and the control group was injected with the same amount of normal saline intraperitoneally.
  • the administration frequency was once every three days for 4 weeks.
  • one male mouse in the model group died, and no major organ abnormalities were found after dissection. It may be due to individual differences that the mice could not tolerate high-concentration iron in the abdominal cavity.
  • mice in the modeling group were divided into five groups: 15 mice in the vehicle (vehicle group) control group, including 8 males and 7 males; 16 mice in the positive drug (deferasirox, 150mg/kg) group, Half male and half male; 16 rats in the compound 2,4-dihydroxybenzoic acid low dose (200 mg/kg) group, half male and half male; 16 rats in the compound 2,4-dihydroxybenzoic acid medium dose (400 mg/kg) group, male and female half; the compound 2,4-dihydroxybenzoic acid high dose (600mg/kg) group included 16 rats, half male and half male.
  • the solvent control group was given intragastric administration of 0.5% methylcellulose 0.2mL once a day for 14 days; the positive drug group was given intragastric administration according to body weight once a day for 14 days; each dose of compound 2,4-dihydroxybenzoic acid According to the body weight, the group was orally administered twice a day, and the administration time was eight o'clock in the morning and eight o'clock in the evening. The drug was stopped every day, and the drug was continued for 9 days after the drug was stopped, and the drug cycle was 14 days in total. The test results are shown in Figure 1-Figure 6.
  • Embodiment 2 clinical iron removal experiment is as follows:
  • the preparation method of the capsules of the product of the present invention Weigh 1000g of 2,4-dihydroxybenzoic acid and 500g of sodium bicarbonate, mix and stir evenly, and put them into capsules.
  • the accurate filling capacity of each capsule is 0.5g.
  • Each capsule contains 0.33g of 2,4-dihydroxybenzoic acid.
  • Patient 3 MDS (myelodysplastic syndrome); patient 4: secondary hemochromatosis; patient 5: MDS; patient 6: AA disease.
  • the serum ferritin value increased by 400 ⁇ g/L.
  • 2,4-dihydroxybenzoic acid has the obvious advantages of short onset time, fast iron-lowering speed and large iron-lowering range.
  • the patients took deferaros to reduce serum ferritin, with an average reduction rate of 38% in 12 months, and an average reduction in serum ferritin value of 372 ⁇ g/L in 3 months.
  • the patient who took 2,4-dihydroxybenzoic acid reduced serum ferritin by more than 50% in one month, which achieved the effect that Degraros could achieve in one year, and the average daily reduction in serum ferritin value exceeded 100 ⁇ g/L.
  • Patient No. 4 The decrease in serum ferritin was the smallest, with a decrease of 1120 ⁇ g/L in one month, but it was much higher than the level of 372 ⁇ g/L in three months of deferaros.
  • 2,4-dihydroxybenzoic acid is far more effective than deferasole in clinical practice. In clinical application, patients often have poor or even ineffective effects after taking deferarost. The main reason is that it is an iron chelating agent with a large molecular weight, and it is often difficult to excrete through the glomerulus within the half-life. 2,4-dihydroxybenzoic acid belongs to the detection agent of iron, its molecular weight is small, there is no excretion obstacle, and there is basically no invalid phenomenon after taking it clinically.
  • the initial serum ferritin value of patient 1 was greater than 40,000 ⁇ g/L, and the serum ferritin value remained basically unchanged after taking Deraros for two months ;
  • the serum ferritin value dropped from more than 40,000 ⁇ g/L to 18354 ⁇ g/L, a decrease of 21646 ⁇ g/L;
  • the initial serum ferritin value of patient No. 5 was 2200 ⁇ g/L, taking After four months of Derarose, the serum ferritin value only dropped to 1600 ⁇ g/L, and then continued to take it for several days, but never dropped below 1000 ⁇ g/L.
  • the serum ferritin value dropped from 1251 ⁇ g/L to 690 ⁇ g/L, and the drop value was 561 ⁇ g/L.
  • 2,4-dihydroxybenzoic acid is clinically safer.
  • Common adverse reactions of Derarose include: diarrhea, vomiting, headache, abdominal pain, fever, rash, increased serum creatinine, etc., as well as increased liver enzymes, elevated transaminases, cough, throat inflammation, urticaria, etc.
  • 2,4-dihydroxybenzoic acid has more advantages than deferaros.
  • the principle of action of Derarose is to compete for iron in serum ferritin in the blood, and finally achieve the purpose of reducing ferritin in cells. There is no balance relationship, and the two can only be connected through free iron ions. Therefore, to solve the problem of iron deposition in Delaros, it is necessary to continuously change several balance systems to achieve the goal.
  • the principle of action of 2,4-dihydroxybenzoic acid is to enter the cell and directly combine with free iron ions. When the iron ions are reduced, the deposited iron will continue to dissolve. This mode of action is more direct, faster and more effective than that of delarose. Targeted, it can not only solve the iron overload caused by blood transfusion, but also cooperate with clinical treatment to effectively solve various diseases caused by iron deposition.
  • Embodiment 3 Example of clinical observation on patients with endogenous iron overload
  • 2,4 dihydroxybenzoic acid can assist in the treatment of diseases related to endogenous iron overload, the clinical trial examples of three common diseases such as diabetes, high uric acid and tumor are given here. Other diseases can also be treated by taking 2,4 dihydroxybenzoic acid. Hydroxybenzoic acid is used for iron-lowering auxiliary disease treatment, which is not listed here.
  • Serum ferritin values for normal adults are: 15-200 ⁇ g/L for males and 12-150 ⁇ g/L for females;
  • the normal value of uric acid is 210-420 ⁇ mol/L for men and 150-360 ⁇ mol/L for women.
  • Serum ferritin values in patients with chronic diseases and common diseases are generally higher than normal values. Reducing the serum ferritin level of such patients can promote and synergize the treatment of the disease. Whether the endogenous iron overload can be reduced is the main problem to be solved at present.
  • the serum ferritin value of diabetic patients is generally higher than the normal value. The higher the ferritin value, the lower the response sensitivity to hypoglycemic drugs and the worse the hypoglycemic effect. In the above table, 18 diabetic patients (9 males and 9 females) took 2,4-dihydroxybenzoic acid for 2 months, and all serum ferritin values decreased without exception.
  • the average value of protein was 243.28 ⁇ g/L, and the average value after taking it for two months was 167.70 ⁇ g/L, an average decrease of 75.58 ⁇ g/L; the average decrease was 31.07%; the average value of serum ferritin in 9 female patients before taking it was 242.67 ⁇ g /L, the average value was 141.82 ⁇ g/L after taking it for two months, an average decrease of 100.85 ⁇ g/L; an average decrease of 41.56%.
  • the decrease of serum ferritin value plays an important role in promoting the treatment of diabetes.
  • Serum ferritin value before taking Serum ferritin value after taking ( ⁇ g/L) 19 female 128.00 (2020.04.01 Xijing value) 91.70 (2020.06.13 county hospital value) 20 male 469.38 (2020.03.30 county hospital value) 65.36 (2020.08.07 County Hospital) twenty one female 239.66 (220.04.01 County Hospital) 28.20 (2020.06.07 County Hospital)
  • the serum ferritin value of tumor patients is generally higher than the normal value, and iron overload is an important factor for drug resistance in tumor patients.
  • the serum ferritin value of tumor patients keeps rising with the development of the disease, and it rarely drops automatically. It is difficult to lower the serum ferritin value.
  • Table 4 after 2 months of taking 2,4-dihydroxybenzoic acid for 3 tumor patients, the serum ferritin values all dropped to normal levels, which improved the clinical symptoms of the tumor patients and improved the clinical treatment effect.
  • Table 5 Change table of serum ferritin value and uric acid value in patients with hyperuricemia
  • the uric acid value of patients with uric acid is generally higher than the normal value of uric acid.

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (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)

Abstract

L'invention concerne une utilisation d'acide 2,4-dihydroxybenzoïque ou d'un composé de sel de celui-ci dans la préparation d'un médicament destiné au traitement de maladies liées à une surcharge en fer. La surcharge en fer comprend une surcharge en fer exogène et une surcharge en fer endogène. Une surcharge en fer exogène fait référence à une surcharge en fer provoquée par une dépendance sur le long terme à la transfusion sanguine. Les maladies associées provoquées par une surcharge en fer exogène sont sélectionnées parmi la thalassémie, le syndrome myélodysplasique, l'anémie myélodysplasique ou l'hémochromatose. Les maladies associées provoquées par une surcharge en fer endogène sont sélectionnées parmi le diabète, l'hypertension, l'hyperlipidémie, l'hyperuricémie, la coronaropathie, l'accident vasculaire cérébral, la sclérose vasculaire, la cirrhose, la fibrose pulmonaire, l'arthrite rhumatismale, l'ostéoporose, la maladie d'Alzheimer, les tumeurs ou le vieillissement.
PCT/CN2022/138376 2021-12-13 2022-12-12 Utilisation d'acide 2,4-dihydroxybenzoïque dans un médicament pour le traitement de maladies liées à une surcharge en fer WO2023109747A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202111518870.4 2021-12-13
CN202111518870.4A CN114191425A (zh) 2021-12-13 2021-12-13 2,4-二羟基苯甲酸在治疗铁过载疾病食品药品中的应用

Publications (1)

Publication Number Publication Date
WO2023109747A1 true WO2023109747A1 (fr) 2023-06-22

Family

ID=80653059

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2022/138376 WO2023109747A1 (fr) 2021-12-13 2022-12-12 Utilisation d'acide 2,4-dihydroxybenzoïque dans un médicament pour le traitement de maladies liées à une surcharge en fer

Country Status (2)

Country Link
CN (1) CN114191425A (fr)
WO (1) WO2023109747A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114191425A (zh) * 2021-12-13 2022-03-18 亚宝药业集团股份有限公司 2,4-二羟基苯甲酸在治疗铁过载疾病食品药品中的应用
CN117122588A (zh) * 2022-05-18 2023-11-28 兰州大学 一种酚酸衍生物用于治疗缺血性脑卒中的应用

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998020905A2 (fr) * 1996-11-08 1998-05-22 Biomedical Frontiers, Inc. Traitement des troubles relatifs a une surcharge en fer
US20030220230A1 (en) * 2002-03-14 2003-11-27 Children's Hospital & Research Center At Oakland Enhancement of iron chelation therapy
US20130056211A1 (en) * 2010-03-02 2013-03-07 Cory Berkland Polyamine-dihydroxybenzoic acid conjugate hydrogels as iron chelators
WO2021057680A1 (fr) * 2019-09-23 2021-04-01 张建国 Application de l'acide 2,4-dihydroxybenzoïque ou d'un isomère de celui-ci dans des maladies ou etats associés provoqués par une surcharge en fer
CN114191425A (zh) * 2021-12-13 2022-03-18 亚宝药业集团股份有限公司 2,4-二羟基苯甲酸在治疗铁过载疾病食品药品中的应用

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20200143715A (ko) * 2018-04-15 2020-12-24 모데차이 체비온 철분 과다의 치료 조성물 및 방법
CN111467329A (zh) * 2020-05-22 2020-07-31 张建国 1,3-二羟基丙酮与2,4-二羟基苯甲酸配伍在治疗癌症食品药品中应用
CN115969829A (zh) * 2023-01-10 2023-04-18 好啦好了(山西)科技有限公司 2，4-二羟基苯甲酸胶囊产品治疗铁过载疾病食品药品中的应用

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998020905A2 (fr) * 1996-11-08 1998-05-22 Biomedical Frontiers, Inc. Traitement des troubles relatifs a une surcharge en fer
US20030220230A1 (en) * 2002-03-14 2003-11-27 Children's Hospital & Research Center At Oakland Enhancement of iron chelation therapy
US20130056211A1 (en) * 2010-03-02 2013-03-07 Cory Berkland Polyamine-dihydroxybenzoic acid conjugate hydrogels as iron chelators
WO2021057680A1 (fr) * 2019-09-23 2021-04-01 张建国 Application de l'acide 2,4-dihydroxybenzoïque ou d'un isomère de celui-ci dans des maladies ou etats associés provoqués par une surcharge en fer
CN114191425A (zh) * 2021-12-13 2022-03-18 亚宝药业集团股份有限公司 2,4-二羟基苯甲酸在治疗铁过载疾病食品药品中的应用

Also Published As

Publication number Publication date
CN114191425A (zh) 2022-03-18

Similar Documents

Publication Publication Date Title
WO2023109747A1 (fr) Utilisation d'acide 2,4-dihydroxybenzoïque dans un médicament pour le traitement de maladies liées à une surcharge en fer
US20140234416A1 (en) Use of ferric citrate in the treatment of chronic kidney disease patients
US5006551A (en) Composition for destroying malignant tumors
AU691617B2 (en) Use of magnesium-based products for the treatment or prophylaxis of neoplastic and autoimmune diseases
CN108025007A (zh) 曲美他嗪在制备防治肝病的药物中的用途
CN107468705A (zh) 一种复方电解质葡萄糖注射液及其制备方法
US20070218126A1 (en) Compositions and Methods for Reducing Inflammation and Pain Associated with Acidosis
CN102302510B (zh) 一种药物组合物及其用途
CN104688760B (zh) 一种由柴胡皂苷a和牛磺酸组成的药物组合物及其用途
RU2372899C2 (ru) Фармацевтическая композиция для лечения псориаза, содержащая l-серин, l-изолейцин, фолиевую кислоту и микроэлементы
WO2019134159A1 (fr) Préparation d'administration à la muqueuse rectale de pulsatilla chinensis (bge.) regel saponin b4 et son procédé de préparation
CN1217721A (zh) 治疗或预防间质膀胱炎的方法
CN106727480A (zh) Fex－3在制备抗肥胖症药物中的应用
EP1437140B1 (fr) Formulation pharmaceutique orale contenant du charbon actif et utilisation de cette formulation
CN109223740A (zh) 一种氨丁三醇有机酸盐的应用
RU2370264C2 (ru) Способ детоксикации организма в хирургии местнораспространенного гипернефроидного рака
EP0530220A1 (fr) Composition pharmaceutique.
CN113244208B (zh) Hpa在制备治疗非酒精性脂肪性肝病药物中的应用
WO2023109826A1 (fr) Utilisation de carbonate d'argent dans la préparation d'un médicament
JP7293492B2 (ja) 尿酸性疾患を予防又は治療するための組成物
WO2008100997A2 (fr) Procédés de traitement ou de prévention d'une cystite hémorragique en utilisant un sel de glycérophosphate
TW201332557A (zh) 一種提升病患肝臟功能之藍藻提取液
TWI698244B (zh) 小分子褐藻醣膠與藻褐素之組合物用於製備改善非酒精性脂肪肝之組成物的用途
KR102470029B1 (ko) 오메가-3 지방산 및 우르소데옥시콜산(udca)을 포함하는 콜레스테롤 담석 예방 또는 치료용 약학적 조성물 및 이의 제조방법
Hyson et al. A severe multisystem reaction to sulindac

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22906492

Country of ref document: EP

Kind code of ref document: A1