Use of iron-containing substances

Abstract

The invention discloses application of an iron-containing substance. The invention finds that the iron-containing substance can be used for preparing the medicine for treating leucopenia and / or thrombocytopenia; the iron-containing substance is selected from myoglobin and a derivative thereof, hemoglobin and a derivative thereof, ferrous sulfate, ferrous fumarate, ferrous gluconate, a polyferose compound, ferrous succinate, iron amino acid chelate, heme, heme iron polypeptide, ferric hydroxide polymaltose, ferrous lactate, ferric pyrophosphate and iron dextran; and one or more of iron hydroxymaltose. The iron-containing substance can effectively increase the number of leukocytes and / or platelets.

Description

Technical Field

[0001] This invention relates to the use of an iron-containing substance. Background Technology

[0002] Myelosuppression caused by cancer treatment drugs (such as chemotherapy drugs, targeted drugs, and immunotherapy drugs) is a common and serious clinical complication. Its core mechanism lies in the direct damage of these drugs to bone marrow hematopoietic stem cells and progenitor cells, or in the disruption of the hematopoietic microenvironment, leading to thrombocytopenia and / or leukopenia. Bone marrow, as the body's primary hematopoietic organ, continuously generates red blood cells, white blood cells, and platelets through the differentiation and proliferation of hematopoietic stem cells. Chemotherapy drugs, by interfering with DNA synthesis or directly disrupting the biological functions of dividing cells, indiscriminately attack highly proliferating cells, including hematopoietic stem cells, leading to myelosuppression. Targeted drugs indirectly interfere with the hematopoietic process by specifically inhibiting signaling pathways. Immune checkpoint inhibitors, by excessively activating T cells and releasing large amounts of inflammatory factors, damage the supporting function of bone marrow stromal cells, indirectly causing hematopoietic stem cell apoptosis or differentiation imbalance.

[0003] Currently, the main treatments for thrombocytopenia include platelet transfusions, recombinant human interleukin-11 (rhIL-11), recombinant human thrombopoietin (rhTPO), and thrombopoietin receptor agonists (TPO-RA). Repeated platelet transfusions may lead to alloimmune reactions or ineffective platelet transfusions. rhIL-11 has significant adverse effects, and the efficacy of repeated rhTPO and TPO-RA transfusions decreases over time. The core strategies for treating drug-induced leukopenia include discontinuing the suspected drug, supportive care, and targeted interventions. Supportive care is necessary for patients with severe neutropenia or concurrent infections. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) can accelerate neutrophil recovery by activating the proliferation and differentiation of bone marrow granulocyte progenitor cells, but it may cause bone pain, allergic reactions, and long-term use carries a potential risk of myelodysplastic syndromes. Granulocyte colony-stimulating factor accelerates neutrophil recovery by stimulating myeloid progenitor cell differentiation, but its effects are limited to the leukocyte lineage and have no direct effect on platelet production.

[0004] CN118027155A discloses the use of a TPOR-binding peptide in the preparation of a drug for treating thrombocytopenia. CN105903020A discloses the use of fullerene and / or metallofullerene micro / nanomaterials in the preparation of a drug or drug carrier having at least one of the following properties: (1) prevention and / or treatment of myelosuppression; (2) prevention and / or treatment of at least one of leukopenia, thrombocytopenia, hemoglobin deficiency, and monocyte deficiency caused by myelosuppression; (3) protection of liver, spleen, and kidney tissues. CN110548133A discloses the use of hemoglobin and hemoglobin derivatives in the preparation of injectable drug formulations for enhancing immune function.

[0005] Currently, there are no reports on the use of iron-containing substances in the treatment of leukopenia and / or thrombocytopenia. Summary of the Invention

[0006] In view of this, the object of the present invention is to provide a use for an iron-containing substance that can effectively increase the number of white blood cells and / or platelets. Preferably, the iron-containing substance of the present invention can increase the number of both white blood cells and platelets simultaneously.

[0007] The present invention achieves the above objectives through the following technical solutions.

[0008] This invention provides the use of an iron-containing substance in the preparation of a medicament for treating leukopenia and / or thrombocytopenia, wherein the iron-containing substance is selected from one or more of myoglobin and its derivatives, hemoglobin and its derivatives, ferrous sulfate, ferrous fumarate, ferrous gluconate, polysaccharide iron complex, ferrous succinate, amino acid chelated iron, heme, heme iron polypeptide, ferric hydroxide polymaltose, ferrous lactate, ferric pyrophosphate, dextran iron, and hydroxymaltose iron.

[0009] The myoglobin derivative is selected from one or more of oxymyoglobin, metmyoglobin, and carboxymyoglobin.

[0010] Hemoglobin derivatives are selected from one or more of carboxyhemoglobin, oxyhemoglobin, methemoglobin, sulfhemoglobin, polymerized hemoglobin, and intramolecular cross-linked hemoglobin.

[0011] According to the use of the invention, preferably, the leukopenia and / or thrombocytopenia are caused by bone marrow suppression.

[0012] According to the use of the invention, preferably, the leukopenia and / or thrombocytopenia are caused by an anti-tumor drug selected from one or more chemotherapy drugs, targeted drugs, and immune checkpoint inhibitors.

[0013] According to the use of the invention, preferably, the iron-containing substance is administered orally.

[0014] According to the use of the invention, preferably, the iron-containing substance is used in a dosage form shown in one of the following:

[0015] (A) Liquid dosage form;

[0016] (B) Solid dosage form.

[0017] According to the intended use of the invention, preferably, the iron-containing substance is used in capsules or oral liquid.

[0018] According to the present invention, preferably, the amount of iron-containing substance added in a unit formulation is 2.5 to 120 mg.

[0019] According to the present invention, preferably, the iron-containing substance is selected from one or more of myoglobin and its derivatives, hemoglobin and its derivatives, polysaccharide iron complex, ferrous sulfate, ferrous lactate, heme iron polypeptide, ferric pyrophosphate, and dextran iron.

[0020] According to the use of the invention, preferably, the iron-containing substance is selected from one of the following:

[0021] (1) Carboxyhemoglobin;

[0022] (2) Oxyhemoglobin and methemoglobin;

[0023] (3) Polysaccharide-iron complex;

[0024] (4) Ferrous sulfate;

[0025] (5) Myoglobin and ferrous lactate;

[0026] (6) Heme iron polypeptide;

[0027] (7) Ferric pyrophosphate;

[0028] (8) Dextran iron.

[0029] According to the present invention, preferably, the ratio of oxyhemoglobin to methemoglobin is (2-10):5, and the ratio of myoglobin to ferrous lactate is (1-8):5; wherein the mass of oxyhemoglobin, methemoglobin, myoglobin and ferrous lactate is based on the mass of iron.

[0030] The iron-containing substance of this invention can effectively increase the number of white blood cells and / or platelets. Furthermore, the iron-containing substance of this invention can simultaneously increase the number of white blood cells and platelets. The iron-containing substance of this invention can be administered orally, improving patient compliance. The iron-containing substance of this invention has high safety and few side effects. Detailed Implementation

[0031] The present invention will be further described below with reference to specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0032] This invention provides the use of an iron-containing substance in the preparation of a medicament for treating leukopenia and / or thrombocytopenia.

[0033] The iron-containing substances of the present invention are selected from one or more of myoglobin and its derivatives, hemoglobin and its derivatives, ferrous sulfate, ferrous fumarate, ferrous gluconate, polysaccharide iron complex, ferrous succinate, amino acid chelated iron, heme, heme iron polypeptide, ferric hydroxide polymaltose, ferrous lactate, ferric pyrophosphate, dextran iron, and hydroxymaltose iron.

[0034] The myoglobin derivative is selected from one or more of oxymyoglobin, metmyoglobin, and carboxymyoglobin. In some embodiments, the muscle protein derivative is selected from one or more of metmyoglobin and carboxymyoglobin.

[0035] The hemoglobin derivative is selected from one or more of carboxyhemoglobin, oxyhemoglobin, methemoglobin, sulfhemoglobin, polymerized hemoglobin, and intramolecularly cross-linked hemoglobin. Preferably, the hemoglobin derivative is selected from one or more of carboxyhemoglobin, oxyhemoglobin, and methemoglobin.

[0036] Myoglobin can be derived from animals. Preferably, myoglobin is derived from mammals. More preferably, myoglobin is derived from humans, pigs, sheep, or cattle. In some embodiments, hemoglobin is derived from pigs or cattle.

[0037] Myoglobin is a recombinant protein obtained through genetic engineering. It can be obtained through in vivo or in vitro methods.

[0038] Hemoglobin can be derived from animals. Preferably, hemoglobin is derived from mammals. More preferably, hemoglobin is derived from humans, pigs, sheep, or cattle. In some embodiments, hemoglobin is derived from pigs or cattle.

[0039] Hemoglobin can be a recombinant protein obtained through genetic engineering. It can be obtained through in vivo or in vitro methods.

[0040] In some embodiments, the iron-containing substance is selected from one or more of myoglobin, oxymyoglobin, hemoglobin, carboxyhemoglobin, oxyhemoglobin, methemoglobin, polysaccharide iron complex, ferrous fumarate, ferrous gluconate, ferrous succinate, ferrous sulfate, ferrous lactate, heme iron polypeptide, ferric pyrophosphate, and dextran iron.

[0041] In some preferred embodiments, the iron-containing substance is selected from one or more of carboxyhemoglobin, oxyhemoglobin, methemoglobin, myoglobin, polysaccharide iron complex, ferrous sulfate, ferrous lactate, heme iron polypeptide, ferric pyrophosphate, and dextran iron.

[0042] In some embodiments, the iron-containing substance is selected from one of the following:

[0043] (1) Carboxyhemoglobin;

[0044] (2) Oxyhemoglobin and methemoglobin;

[0045] (3) Polysaccharide-iron complex;

[0046] (4) Ferrous sulfate;

[0047] (5) Myoglobin and ferrous lactate;

[0048] (6) Heme iron polypeptide;

[0049] (7) Ferric pyrophosphate;

[0050] (8) Dextran iron.

[0051] In this invention, the ratio of oxyhemoglobin to methemoglobin can be (2-10):5; preferably (3-8):5; more preferably (5-7):5. The mass of both oxyhemoglobin and methemoglobin is based on the mass of iron.

[0052] In this invention, the ratio of myoglobin to ferrous lactate can be (1-8):5; preferably (2-6):5; more preferably (3-5):5. The mass of both myoglobin and ferrous lactate is based on the mass of iron.

[0053] The iron-containing substances mentioned above can effectively increase the number of white blood cells and / or platelets.

[0054] In some embodiments, the present invention provides the use of an iron-containing substance in the preparation of a medicament for treating leukopenia.

[0055] In other embodiments, the present invention provides the use of an iron-containing substance in the preparation of a medicament for treating thrombocytopenia.

[0056] In some other embodiments, the present invention provides the use of an iron-containing substance in the preparation of a medicament for treating leukopenia and thrombocytopenia.

[0057] The iron-containing substance of the present invention can increase the number of white blood cells and platelets, either individually or simultaneously, thereby reducing the risk of drug interactions and treatment costs.

[0058] In some embodiments, the present invention provides the use of an iron-containing substance in the preparation of a medicament for treating leukopenia and / or thrombocytopenia, said iron-containing substance being selected from one or more of carboxyhemoglobin, oxyhemoglobin and methemoglobin, iron polysaccharide complexes, ferrous sulfate, myoglobin and ferrous lactate. Preferably, the iron-containing substance is selected from one or more of carboxyhemoglobin, myoglobin and ferrous lactate, and ferrous sulfate. More preferably, the iron-containing substance is carboxyhemoglobin.

[0059] In other embodiments, the present invention provides the use of an iron-containing substance in the preparation of a medicament for treating thrombocytopenia, wherein the iron-containing substance is selected from one or more of heme iron polypeptide, ferric pyrophosphate, and dextran iron. Preferably, the iron-containing substance is selected from one or more of heme iron polypeptide and ferric pyrophosphate. More preferably, the iron-containing substance is heme iron polypeptide.

[0060] In this invention, the leukopenia and / or thrombocytopenia may be caused by bone marrow suppression.

[0061] In this invention, the leukopenia and / or thrombocytopenia can be caused by tumor treatment drugs. Tumor treatment drugs can be selected from chemotherapy drugs, targeted drugs, or immune checkpoint inhibitors. Preferably, the leukopenia and / or thrombocytopenia are caused by chemotherapy drugs.

[0062] Chemotherapy drugs can be selected from one or more of alkylating agents and antimetabolites.

[0063] Examples of alkylating agents include, but are not limited to, cyclophosphamide, ifosfamide, carmustine, lomustine, cisplatin, carboplatin, busulfan, and dacarbazine. According to one embodiment of the invention, the alkylating agent is cyclophosphamide.

[0064] Antimetabolites may be selected from one or more of folic acid antagonists, purine antagonists, pyrimidine antagonists, and cladribine. Examples of folic acid antagonists include, but are not limited to, methotrexate and pemetrexed. Examples of purine antagonists include, but are not limited to, mercaptopurine and fludarabine. Examples of pyrimidine antagonists include, but are not limited to, 5-fluorouracil, capecitabine, gemcitabine, and cytarabine. According to one embodiment of the present invention, the antimetabolite is 5-fluorouracil.

[0065] Examples of targeted therapies include, but are not limited to, PI3K inhibitors and CDK4 / 6 inhibitors. Examples of CDK4 / 6 inhibitors include, but are not limited to, palbociclib, reboxiclib, abeciclib, and dalciribé. Examples of PI3K inhibitors include, but are not limited to, apeliximab, duverithione, ederaglixil, and cobimetinib.

[0066] Immune checkpoint inhibitors can be PD-1 / PD-L1 monoclonal antibodies. Examples of PD-1 / PD-L1 monoclonal antibodies include, but are not limited to, tislelizumab, nivolumab, pentazolizumab, atezolizumab, duvastatin, and acimetidine.

[0067] The iron-containing substance of this invention is administered orally. Currently, drugs for treating leukopenia or thrombocytopenia are typically administered subcutaneously or intravenously, which are difficult to administer, cause patient discomfort, and result in low patient compliance. The iron-containing substance of this invention, administered orally, improves patient compliance.

[0068] The iron-containing substance of the present invention can be used in the form of liquid or solid dosage forms. It can be used in the form of oral liquids, capsules, tablets, or granules. Preferably, the iron-containing substance of the present invention is used in the form of capsules or oral liquids. Examples of capsules include, but are not limited to, hard capsules and soft capsules. The capsule dosage form helps to ensure that the iron in the iron-containing substance exists in the form of ferrous ions, thereby improving the absorption rate of ferrous ions.

[0069] The active ingredient in a pharmaceutical preparation containing iron may be solely the iron-containing substance of this invention, or it may contain other active ingredients. In addition to the active ingredient, the pharmaceutical preparation may also contain excipients.

[0070] Examples of excipients include, but are not limited to, capsule forming materials, plasticizers, preservatives, colorants, lubricants, thickeners, and stabilizers. Examples of capsule forming materials include, but are not limited to, gelatin and cellulose. Examples of plasticizers include, but are not limited to, diethyl phthalate and propylene glycol. Examples of preservatives include, but are not limited to, benzoic acid, sodium benzoate, sorbic acid, potassium sorbate, parabens, and calcium propionate. Examples of colorants include, but are not limited to, amaranth, brilliant blue, carmine, tartrazine, and sunset yellow. Examples of lubricants include, but are not limited to, magnesium stearate, microcrystalline silica gel, talc, hydrogenated vegetable oil, polyethylene glycol, and magnesium lauryl sulfate. Examples of thickeners include, but are not limited to, starch, modified starch, lactose, microcrystalline cellulose, and sodium carboxymethyl cellulose. Examples of stabilizers include, but are not limited to, sodium bisulfite, ascorbic acid, tert-butylhydroxyanisole, and butylated hydroxytoluene.

[0071] The amount of iron-containing substance can be 0.05–2 mg / kg; preferably 0.6–1.5 mg / kg; more preferably 0.9–1.2 mg / kg, and the mass of the iron-containing substance is based on the mass of iron element contained therein.

[0072] In a unit formulation, the amount of iron-containing substance added is 2.5–120 mg, preferably 10–60 mg; more preferably 15–30 mg.

[0073] The following describes the drugs used in the examples:

[0074] Cyclophosphamide (CTX): Trade name Andosheng, purchased from Baxter Oncology GmbH (Germany).

[0075] Polyethylene glycol-modified recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) injection: trade name Xinruibai, purchased from Qilu Pharmaceutical Co., Ltd.

[0076] Recombinant human interleukin-11 for injection (rhIL-11): Trade name Juheli, purchased from Qilu Pharmaceutical Co., Ltd.

[0077] Fluorouracil injection: purchased from Southwest Pharmaceutical Co., Ltd.

[0078] Polysaccharide Iron Complex (PIC) Capsules: Trade name Hongyuanda, purchased from Shanghai Pharmaceuticals Group Qingdao Guofeng Pharmaceutical Co., Ltd.

[0079] Ferrous sulfate (Fe2SO4) tablets were purchased from Shanxi Lijiu Pharmaceutical Co., Ltd.

[0080] Heme iron polypeptide, purchased from Newroots, Canada.

[0081] Ferric pyrophosphate was purchased from Guangdong Kangda Biotechnology Co., Ltd.

[0082] Dextran iron dispersible tablets, marketed as Huatai Xiesusheng, were purchased from Jiangxi Huatai Pharmaceutical Co., Ltd.

[0083] Carboxyhemoglobin solution is a physiological saline solution of carboxyhemoglobin (COHb) with a concentration of 0.2 mg / mL. The mass of carboxyhemoglobin is expressed as the mass of iron.

[0084] The oxyhemoglobin-methemoglobin mixture is a physiological saline solution of oxyhemoglobin (O2Hb) and methemoglobin (MetHb). The concentration of oxyhemoglobin is 0.14 mg / mL, and the concentration of methemoglobin is 0.1 mg / mL. The mass of both oxyhemoglobin and methemoglobin is expressed as the mass of iron.

[0085] The myoglobin (Mb)-ferrous lactate (FL) mixture is an aqueous solution of myoglobin and ferrous lactate. The concentration of myoglobin is 0.3 mg / mL, and the concentration of ferrous lactate is 0.5 mg / mL. The mass of both myoglobin and ferrous lactate is expressed as the mass of iron.

[0086] The aforementioned hemoglobin or myoglobin are all derived from pigs.

[0087] The test methods used in the embodiments are described below:

[0088] Platelet count was tested using the following method:

[0089] 1. Prepare a diluted solution of procaine hydrochloride: Take 2g of procaine hydrochloride, add distilled water to make up to 100mL, mix well and filter, and store at 4℃.

[0090] 2. Add diluent: Take a test tube and accurately add 380 μL of procaine hydrochloride diluent.

[0091] 3. Blood collection and addition: Fix the rat to be tested, locate the tail vein, wipe the blood collection site once with warm water and once with alcohol, use a syringe to puncture the rat's tail vein, wipe away the first drop of blood, and use a pipette to draw 20μL of venous whole blood and add it to the test tube.

[0092] 4. Hemolysis and standing: Shake the test tube thoroughly for 2-3 minutes to dilute the red blood cells, then let it stand for 5-10 minutes to obtain a well-mixed cell suspension.

[0093] 5. Filling the cell: Use a pipette to draw a small amount of the mixed cell suspension. Wipe the counting chamber and coverslip clean with a soft cloth, and place the coverslip firmly over the counting cell. Place the tip of the pipette close to the edge where the counting chamber and coverslip meet, allowing the liquid to fill the counting cell naturally through capillary action. Let it stand for 10-15 minutes before counting.

[0094] 6. Microscopic Counting: Under high magnification (10×40), use dark-field method or reduce the aperture to increase contrast, and count all platelets in the five middle squares within the large central square. The counting follows the principle of "counting the top, not the bottom; counting the left, not the right."

[0095] Total platelet count / L = Total platelet count (N) in 5 squares × 5 × 10 × 20 × 10 6 / L

[0096] White blood cell count was tested using the following method:

[0097] 1. Prepare leukocyte diluent: Take 2 mL of glacial acetic acid and dilute with distilled water to 100 mL to prepare a 2% glacial acetic acid diluent.

[0098] 2. Add diluent: Take a small test tube and accurately add 0.38 mL of white blood cell diluent.

[0099] 3. Blood Collection and Addition: Fix the rat to be tested, locate the tail vein, and wipe the blood collection site once with warm water and once with alcohol. Use a syringe to puncture the rat's tail vein, wipe away the first drop of blood, and use a pipette to draw 20 μL of venous whole blood. Gently blow the blood into the leukocyte diluent at the bottom of the test tube, and repeat the blowing and washing 2-3 times to obtain a well-mixed cell suspension.

[0100] 4. Filling the cell: Use a pipette to draw a small amount of the well-mixed cell suspension. Wipe the counting chamber and coverslip clean with a soft cloth, and place the coverslip firmly over the counting cell. Place the tip of the pipette close to the edge where the counting chamber and coverslip meet, allowing the liquid to fill the counting cell naturally through capillary action. Let it stand for 2-3 minutes before counting.

[0101] 5. Microscopic Counting: Locate the grid of the counting cell under low magnification (10×10). Switch to high magnification (10×40) to count. Count all white blood cells in the four large squares at the four corners. Follow the principle of "counting the top but not the bottom, counting the left but not the right".

[0102] White blood cell count / L = [Total white blood cells in 4 large squares (N) / 4] × 10 × 20 × 10 6 / L

[0103] Example 1

[0104] Forty-eight SD rats (weighing 250±5g, half male and half female) were used and injected intraperitoneally with cyclophosphamide (CTX) for three consecutive days at a daily dose of 50mg / kg to induce leukopenia and thrombocytopenia, thus obtaining rats with model status.

[0105] After modeling, rats were randomly divided into 8 groups: negative control group, rhG-CSF group, rhIL-11 group, COHb group, O2Hb+MetHb group, PIC group, Fe2SO4 group, and Mb+FL group.

[0106] The negative control group received no treatment during days 4–10.

[0107] The rhG-CSF group received a single intraperitoneal injection of PEG-rhG-CSF (pegylated recombinant human granulocyte colony-stimulating factor) on the fourth day, at a dose of 0.63 mg / kg (calculated as PEG-rhG-CSF).

[0108] The rhIL-11 group received intraperitoneal injection of recombinant human interleukin-11 (rhIL-11) once daily from the fourth to the tenth day, at a dose of 0.15 mg / kg (calculated as recombinant human interleukin-11).

[0109] The COHb group was given carboxyhemoglobin (COHb) solution once daily by gavage from the fourth to the tenth day, at a dose of 1.0 mg / kg per day (based on the mass of iron).

[0110] The O2Hb+MetHb group was given a mixture of oxyhemoglobin (O2Hb) and methemoglobin (MetHb) by gavage once a day from the fourth to the tenth day. The dosage of oxyhemoglobin was 0.7 mg / kg per day (based on the mass of iron) and the dosage of methemoglobin was 0.5 mg / kg per day (based on the mass of iron).

[0111] The PIC group received polysaccharide-iron complex capsules once daily by gavage from day 4 to day 10, at a dose of 0.8 mg / kg (based on the mass of iron).

[0112] The Fe2SO4 group was given ferrous sulfate tablets once daily by gavage from the fourth to the tenth day. The dosage of Fe2SO4 was 1.4 mg / kg per day (based on the mass of iron).

[0113] The Mb+FL group received a myoglobin (Mb)-ferrous lactate mixture once daily by gavage from day 4 to day 10. The dosage of myoglobin was 0.3 mg / kg (based on the mass of iron) per day, and the dosage of ferrous lactate was 0.5 mg / kg (based on the mass of iron) per day.

[0114] The platelet and white blood cell counts of rats in each group were measured during the experiment, and the results are shown in Tables 1 and 2.

[0115] Table 1 Platelet count (unit: ×10) 9 (pieces / L)

[0116]

[0117] Table 2 White blood cell count (unit: ×10) 9 (pieces / L)

[0118]

[0119] Note: The initial state in Tables 1 and 2 refers to the platelet or white blood cell count of rats without any treatment. The initial state and 3-day data in the tables are averages for all rats, and the 7-day and 10-day data are averages for each group of rats.

[0120] As shown in Tables 1 and 2, after three consecutive days of cyclophosphamide injection, the platelet and white blood cell counts of rats in all groups decreased significantly, indicating successful model establishment. After seven consecutive days of administration, the platelet and white blood cell counts in the COHb, O2Hb+MetHb, PIC, Fe2SO4, and Mb+FL groups all increased significantly, demonstrating that the iron-containing substance of this invention can be used to treat leukopenia and / or thrombocytopenia.

[0121] Example 2

[0122] Thirty SD rats (weighing 250±5g, half male and half female) were used and injected intraperitoneally with fluorouracil injection solution at a dose of 70mg / kg to induce thrombocytopenia. The model rats were obtained 7 days after the injection.

[0123] After modeling, rats were randomly divided into 5 groups and fed for another week. The five groups were the negative control group, rhIL-11 group, heme iron polypeptide group, ferric pyrophosphate group, and dextran iron group.

[0124] During the following week of continued feeding, the five groups were treated as follows:

[0125] Negative control group: No treatment was given.

[0126] rhIL-11 group: Recombinant human interleukin-11 (rhIL-11) was administered via intraperitoneal injection once daily at a dose of 0.15 mg / kg (calculated as recombinant human interleukin-11).

[0127] Heme iron polypeptide group: Heme iron polypeptide was administered by gavage once a day at a dose of 1.4 mg / kg (based on the mass of iron).

[0128] Ferric pyrophosphate group: Ferric pyrophosphate was administered once daily by gavage at a dose of 1.0 mg / kg (based on the mass of iron).

[0129] Dextran iron group: Dextran iron dispersible tablets were administered by gavage once a day, with a dosage of 0.9 mg / kg per day (based on the mass of iron).

[0130] Platelet counts were measured in each group of rats under the initial conditions, after modeling, and during the following week of continued feeding. The results are shown in Table 3.

[0131] Table 3 Platelet Count (Unit: ×10) 9 (pieces / L)

[0132]

[0133] Note: Initial state refers to the platelet count of rats without any treatment. The data in the table for initial state and after modeling are the average values ​​for all rats, while the data for 3 days and 7 days are the average values ​​for each group of rats.

[0134] Table 3 shows that the platelet count in each group of rats decreased significantly after injection of fluorouracil, indicating successful model establishment. The platelet counts in the heme iron polypeptide group, ferric pyrophosphate group, and dextran iron group increased significantly after 7 days of continuous administration, demonstrating that the iron-containing substance of this invention can be used to treat thrombocytopenia.

[0135] This invention is not limited to the above-described embodiments. Any modifications, improvements, or substitutions that can be conceived by those skilled in the art without departing from the essential content of this invention fall within the scope of this invention.

Claims

1. The use of an iron-containing substance in the preparation of a medicament for treating leukopenia and / or thrombocytopenia, characterized in that, The iron-containing substance is selected from one or more of myoglobin and its derivatives, hemoglobin and its derivatives, ferrous sulfate, ferrous fumarate, ferrous gluconate, polysaccharide iron complex, ferrous succinate, amino acid chelated iron, heme, heme iron polypeptide, ferric hydroxide polymaltose, ferrous lactate, ferric pyrophosphate, dextran iron, and hydroxymaltose iron. The myoglobin derivative is selected from one or more of oxymyoglobin, metmyoglobin, and carboxymyoglobin. Hemoglobin derivatives are selected from one or more of carboxyhemoglobin, oxyhemoglobin, methemoglobin, sulfhemoglobin, polymerized hemoglobin, and intramolecular cross-linked hemoglobin.

2. The use according to claim 1, characterized in that, The leukopenia and / or thrombocytopenia are caused by bone marrow suppression.

3. The use according to claim 1, characterized in that, The leukopenia and / or thrombocytopenia are caused by tumor treatment drugs, which are selected from one or more of chemotherapy drugs, targeted drugs, and immune checkpoint inhibitors.

4. The use according to claim 1, characterized in that, The iron-containing substance is administered orally.

5. The use according to claim 1, characterized in that, The iron-containing substance is used in one of the following dosage forms: (A) Liquid dosage form; (B) Solid dosage form.

6. The use according to claim 5, characterized in that, The iron-containing substance is used in capsules or oral liquids.

7. The use according to claim 1, characterized in that, In a unit formulation, the amount of iron-containing substance added is 2.5–120 mg.

8. The use according to claim 1, characterized in that, The iron-containing substance is selected from one or more of myoglobin and its derivatives, hemoglobin and its derivatives, polysaccharide iron complex, ferrous sulfate, ferrous lactate, heme iron polypeptide, ferric pyrophosphate, and dextran iron.

9. The use according to claim 1, characterized in that, The iron-containing substance is selected from one of the following: (1) Carboxyhemoglobin; (2) Oxyhemoglobin and methemoglobin; (3) Polysaccharide-iron complex; (4) Ferrous sulfate; (5) Myoglobin and ferrous lactate; (6) Heme iron polypeptide; (7) Ferric pyrophosphate; (8) Dextran iron.

10. The use according to claim 9, characterized in that, The ratio of oxyhemoglobin to methemoglobin is (2-10):5, and the ratio of myoglobin to ferrous lactate is (1-8):5; wherein, the mass of oxyhemoglobin, methemoglobin, myoglobin and ferrous lactate are all based on the mass of iron.

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