Use of zanamivir in the preparation of a medicament for treating or preventing preeclampsia

Abstract

The present invention provides a use of zanamivir in the preparation of a drug for treating or preventing preeclampsia, as well as the drug and a method for treatment. Zanamivir can effectively improve the symptoms of preeclampsia, such as high blood pressure, proteinuria, elevated creatinine, neuraminidase, and sialic acid, increase NO levels, and improve pregnancy outcomes. Zanamivir shows better efficacy when used in combination with hydroxyprogesterone caproate.

Description

[Technical field]

[0001] [CROSS REFERENCE TO RELATED APPLICATIONS] This application claims priority to a Chinese patent application filed with the China Patent Office on November 24, 2020, bearing application number 202011331782.9 and entitled "Method for Treating Preeclampsia," the entire contents of which are incorporated herein by reference.

[0002] This application claims priority to a Chinese patent application filed with the China Patent Office on December 1, 2020, bearing application number 202011388482.4 and entitled "Method for Treating Preeclampsia," the entire contents of which are incorporated herein by reference.

[0003] This application claims priority to a Chinese patent application filed with the China Patent Office on November 24, 2021, bearing application number 202111400709.7 and entitled "Use of Zanamivir in Preparing a Medicament for Treating or Preventing Preeclampsia," the entire contents of which are incorporated herein by reference.

[0004] [Technical field] The present application provides the use of zanamivir in the preparation of a medicament for treating or preventing pre-eclampsia, such a medicament, and a method of treatment. [Background technology]

[0005] Preeclampsia, also known as preeclampsia or pregnancy toxemia, is a clinical syndrome that appears after the 20th week of pregnancy, with high blood pressure, proteinuria and edema as its main symptoms, accompanied by headache, blurred vision, vomiting, abdominal discomfort, etc. Preeclampsia not only affects fetal development, but also often endangers the life safety of pregnant women. According to statistics, preeclampsia affects about 8.5 million pregnant women worldwide every year, resulting in about 63,000 maternal and infant deaths and about 500,000 infant deaths, and is one of the important factors causing morbidity and mortality of pregnant women and infants. There is also evidence that the incidence of preeclampsia is higher in developing countries, about 9.4% in China. The pathological process of this disease can be roughly divided into two stages. 1) Abnormal placentation, especially uterine spiral arteriolar dilation disorder, affects the blood flow supply from the mother to the fetus. Reduced placental blood perfusion activates placental release-related cytokines, leading to changes in systemic hemodynamics. 2) Pregnant women develop clinical symptoms that are primarily due to circulatory disorders caused by dysfunction of maternal vascular endothelial cells, including altered vascular reactivity, activation of the coagulation cascade, and destruction of vascular integrity. Preeclampsia affects most organs in pregnant women, but primarily affects the kidneys, liver, and brain.

[0006] There has been a large amount of preclinical and clinical research on preeclampsia, but at present, its pathogenesis is known to be complex, but is still unclear, and the relevant treatment methods are quite scarce, and generally only blood pressure reduction, diuresis, sedative treatment, etc. according to the disease condition are used. When severe eclampsia appears, magnesium sulfate can be used to eliminate convulsive symptoms, and currently, terminating pregnancy is still the most effective clinical treatment measure. In addition to polygenic genetic factors, the etiology of preeclampsia may cause cell immune abnormalities due to susceptibility factors, placental and trophoblast hypoxia and ischemia, oxidative stress response abnormalities, and secondary systemic vascular endothelial cell damage, which may lead to the occurrence of this disease. For this reason, in order to elucidate the pathogenesis of preeclampsia, a series of mechanism theories have been proposed in the scientific community, including the placental and trophoblast ischemia theory, oxidative stress theory, immune dysregulation theory, genetic theory, and vascular endothelial damage theory. Placental spiral arteriolar remodeling disorder and shallow placental implantation, hypoxia and ischemia of trophoblasts, and damage to vascular endothelial cells are usually considered to be the pathophysiological basis of the onset of preeclampsia. A large amount of research has shown that hypoxia and ischemia in the placenta and the release of angiogenic circulating factors, including vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor-1 (sFlt-1), angiotensin II receptor 1 autoantibodies and tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and IL-6, pentraxin 3 (PTX3), etc., can cause damage to maternal vascular endothelial function through different pathways. In addition, the ratio of vasodilator and vasoconstrictor in the blood of preeclampsia patients is inconsistent, and the damage to the vascular endothelium increases the sensitivity of blood vessels to vasoconstrictors and decreases the sensitivity to vasodilator, resulting in systemic arteriolar spasm. Patients with hypertension, diabetes, obesity, and hyperlipidemia may have oxidative stress and vascular endothelial dysfunction before pregnancy, making them more susceptible to developing preeclampsia after pregnancy.

[0007] Vascular endothelial cells are distributed on the luminal surface of blood vessels and are the direct receivers and responders of flow shear force. Endothelial cells convert extracellular mechanical signals into intracellular signals through various pathways, and further induce downstream biochemical reactions. The endothelial cell glycocalyx is a villus-like polysaccharide-protein complex located on the apical membrane of endothelial cells. It is interposed between the vascular wall and blood, and is a dynamic natural barrier on the endothelial cell surface, mediating the force-transmitting function of endothelial cells. The endothelial cell glycocalyx is a highly negatively charged endothelial cell surface layer composed of oligosaccharide chain glycoproteins with terminal sialic acid residues and proteoglycans with glycosaminoglycan side chains. In addition to being a selective permeability barrier of the vascular wall, regulating the rheological properties of the microcirculation, and participating in vascular protection and signal transduction, a large amount of evidence has demonstrated that the endothelial cell glycocalyx is also involved in the sensing and transmission of flow shear force. Manolis et al. used a selective enzymatic degradation method to simultaneously selectively degrade sialic acid, heparin sulfate, chondroitin sulfate, and hyaluronic acid in the glycocalyx, and found that the synthesis of nitric oxide (NO) induced by flow shear stress was inhibited in bovine thoracic aortic endothelial cells, indicating that an intact glycocalyx plays an important role in shear stress-induced NO synthesis. Studies have also confirmed that when the glycocalyx is intact and intact, flow shear stress is transmitted to the actin cytoskeleton via the core protein or directly to the cell membrane via the core protein, mediating downstream signaling, such as NO production and cytoskeleton recombination. On the other hand, when the glycocalyx is damaged, the normal function of vascular endothelial cells is affected. Recent clinical studies have detected more glycocalyx degradation in patients with early-onset preeclampsia, and, along with increased levels of heparan sulfate proteoglycan and hyaluronic acid, which are glycocalyx components, in the blood, it has been shown that vascular endothelial glycocalyx degradation is closely related to the development of early-onset preeclampsia.

[0008] Degradation of vascular endothelial glycocalyx is usually mediated by a variety of specific enzymes. Neuraminidase, also known as sialidase, acts on oligosaccharide glycoproteins containing sialic acid residues at the glycocalyx end, hydrolyzing the ketoglycosidic bond to release sialic acid, ultimately causing glycocalyx degradation and corresponding damage to vascular endothelial function. Some literature has demonstrated that elevated neuraminidase levels can be detected in the blood of patients with some cardiovascular-related diseases, such as type II diabetes, and that inhibiting neuraminidase can improve vascular endothelial function and the overall function of the cardiovascular system by inhibiting glycocalyx degradation. At present, there is no effective drug in clinical practice for the prevention and treatment of preeclampsia, and there is a great demand in the field for drugs used to prevent and treat this disease. Drugs that inhibit neuraminidase provide a completely new concept and means for the development of drugs to prevent and treat preeclampsia. Summary of the Invention

[0009] In one aspect, the present application relates to the use of zanamivir in the preparation of a medicament for treating or preventing pre-eclampsia, comprising: The zanamivir provided uses include the compound zanamivir and its medically or pharma- ceutically acceptable derivatives or salts.

[0010] Furthermore, the dosage form of the drug is an injection, an oral preparation or an external preparation, preferably an injection or an oral preparation, and particularly preferably an injection.

[0011] Furthermore, the injection preparations include injection liquids and powder injections, the oral preparations include tablets, capsules, oral liquids, throat sprays or nasal sprays, and the external preparations include ointments, sprays and patches.

[0012] Further, the treatment or prevention of preeclampsia includes improvement of headache, dizziness, nausea, vomiting, abdominal discomfort, hypertension, proteinuria, edema, liver and kidney function, thrombocytopenia and / or coagulation system abnormalities; increased creatinine, neuraminidase and sialic acid, decreased blood NO level; and improvement of pregnancy outcome.

[0013] In another aspect, the present application provides a method for treating or preventing pre-eclampsia comprising administering zanamivir to a patient at risk for or suffering from pre-eclampsia.

[0014] Furthermore, the dosage form of the zanamivir is an injection, an oral preparation or an external preparation, preferably an injection or an oral preparation, and particularly preferably an injection.

[0015] The injection preparations include injection liquids and powder injections, the oral preparations include tablets, capsules, oral liquids, throat or nose sprays, and the external preparations include ointments, sprays, and patches.

[0016] Further, the treatment or prevention of preeclampsia includes improvement of headache, dizziness, nausea, vomiting, abdominal discomfort, hypertension, proteinuria, edema, liver and kidney function, thrombocytopenia and / or coagulation system abnormalities; increased creatinine, neuraminidase and sialic acid, decreased blood NO level; and improvement of pregnancy outcome.

[0017] Furthermore, the method of administration of said zanamivir is optionally intramuscular injection, intravenous injection, intravenous drip infusion, preferably intramuscular injection, administered 1 to 7 times, preferably 1 to 4 times, more preferably 1 to 2 times per week, and the duration of administration is 1 to 30 days, preferably 1 to 7 days, more preferably 1 to 7 days.

[0018] In another aspect, the present application provides a medicament for treating or preventing pre-eclampsia.

[0019] Furthermore, the dosage form of the drug is an injection, an oral preparation or an external preparation, preferably an injection or an oral preparation, particularly preferably an injection, and further preferably an intramuscular injection.

[0020] Further, the drug includes instructions stating that the method of administration of zanamivir is 1 to 7 times a week, preferably 1 to 4 times a week, and more preferably 1 to 2 times a week, and the duration of administration is 1 to 30 days, preferably 1 to 7 days, and more preferably 1 to 7 days.

[0021] Further, the treatment or prevention of preeclampsia includes improvement of headache, dizziness, nausea, vomiting, abdominal discomfort, hypertension, proteinuria, edema, liver and kidney function, thrombocytopenia and / or coagulation system abnormalities; increased creatinine, neuraminidase and sialic acid, decreased blood NO level; and improvement of pregnancy outcome.

[0022] Furthermore, when the methods or medicaments of the present application are administered, the dosage is 20-40 mg / day, 90 mg / kg, or 120 mg / kg, preferably 20 mg / day.

[0023] Additionally, the drug further comprises pharma- ceutically acceptable excipients, including, but not limited to, solvents, cosolvents, stabilizers, dispersants, viscosity modifiers, antioxidants, sweeteners, binders, and gas generating agents.

[0024] Additionally, zanamivir may be the only active ingredient in the method or medicament, or the method may further comprise administering other active ingredients, or the medicament may further comprise other active ingredients, including, but not limited to, antihypertensive drugs, protein supplements, anti-vertigo drugs, and drugs for treating cardiovascular disease.

[0025] In another aspect, the present application provides the use of a neuraminidase inhibitor in the preparation of a medicament for treating or preventing pre-eclampsia.

[0026] The neuraminidase inhibitors include the compound neuraminidase inhibitors and medically or pharma- ceutically acceptable derivatives or salts thereof.

[0027] Furthermore, the dosage form of the drug is an injection, an oral preparation or an external preparation, preferably an injection or an oral preparation, and particularly preferably an injection.

[0028] Furthermore, the injection preparations include injection liquids and powder injections, the oral preparations include tablets, capsules, oral liquids, throat sprays or nasal sprays, and the external preparations include ointments, sprays and patches.

[0029] Further, the treatment or prevention of preeclampsia includes improvement of headache, dizziness, nausea, vomiting, abdominal discomfort, hypertension, proteinuria, edema, liver and kidney function, thrombocytopenia and / or coagulation system abnormalities; increased creatinine, neuraminidase and sialic acid, decreased blood NO level; and improvement of pregnancy outcome.

[0030] In another aspect, the present application provides a method for treating or preventing pre-eclampsia comprising administering a neuraminidase inhibitor to a patient at risk for or suffering from pre-eclampsia.

[0031] Furthermore, the dosage form of the neuraminidase inhibitor includes an injection, an oral preparation, or an external preparation, preferably an injection or an oral preparation, and particularly preferably an injection.

[0032] The injection preparations include injection liquids and powder injections, the oral preparations include tablets, capsules, oral liquids, throat sprays or nasal sprays, and the external preparations include ointments, sprays and patches.

[0033] Further, the treatment or prevention of preeclampsia includes improvement of headache, dizziness, nausea, vomiting, abdominal discomfort, hypertension, proteinuria, edema, liver and kidney function, thrombocytopenia and / or coagulation system abnormalities; increased creatinine, neuraminidase and sialic acid, decreased blood NO level; and improvement of pregnancy outcome.

[0034] Furthermore, the method of administration of the neuraminidase inhibitor is optionally intramuscular injection, intravenous injection, or intravenous drip, preferably intramuscular injection, administered 1 to 7 times, preferably 1 to 4 times, more preferably 1 to 2 times per week, and the duration of administration is 1 to 30 days, preferably 1 to 7 days, more preferably 1 to 7 days.

[0035] In another aspect, the present application provides a medicament for treating or preventing pre-eclampsia.

[0036] Furthermore, the dosage form of the drug is an injection, an oral preparation or an external preparation, preferably an injection or an oral preparation, particularly preferably an injection, and further preferably an intramuscular injection.

[0037] Furthermore, the drug includes an instruction manual stating that the method of administration of the neuraminidase inhibitor is 1 to 7 times a week, preferably 1 to 4 times a week, and more preferably 1 to 2 times a week, and the duration of administration is 1 to 30 days, preferably 1 to 7 days, and more preferably 1 to 7 days.

[0038] Further, the treatment or prevention of preeclampsia includes improvement of headache, dizziness, nausea, vomiting, abdominal discomfort, hypertension, proteinuria, edema, liver and kidney function, thrombocytopenia and / or coagulation system abnormalities; increased creatinine, neuraminidase and sialic acid, decreased blood NO level; and improvement of pregnancy outcome.

[0039] Furthermore, when the methods or medicaments of the present application are administered, the dosage is 20-40 mg / day, 90 mg / kg, or 120 mg / kg, preferably 20 mg / day.

[0040] Additionally, the drug further comprises pharma- ceutically acceptable excipients, including, but not limited to, solvents, cosolvents, stabilizers, dispersants, viscosity modifiers, antioxidants, sweeteners, binders, and gas generating agents.

[0041] Moreover, the neuraminidase inhibitor may be the only active ingredient of the method or medicament, or the method may further comprise administering other active ingredients or the medicament may further comprise other active ingredients, including, but not limited to, antihypertensive drugs, protein supplements, anti-vertigo drugs, and drugs for treating cardiovascular disease.

[0042] The zanamivir of the present application is not limited to the chemical structure of CAS number 139110-90-8 (i.e., 5-acetylamino-4-[(aminoiminomethyl)-amino]-2,6-hydro-3,4,5-trideoxy-D-glycerol-D-galactose-2-enolic acid, or 4-guanidino-2-deoxy-2,3-didehydro-N-acetylneuraminic acid), but also includes other medically or pharma- ceutical acceptable derivatives or salts. The neuraminidase inhibitor of the present application refers to a compound or composition having an activity of inhibiting neuraminidase, and includes various neuraminidase inhibitors known in the art and under investigation, including, but not limited to, zanamivir.

[0043] As used herein, hydroxyprogesterone caproate is also known as 17-alpha hydroxyprogesterone caproate, 17-HPC, 17-hydroxyprogesterone caproate, 17-hydroxyprogesterone caproate, and has the CAS number 630-56-8.

[0044] The preeclampsia of the present application is a clinical syndrome during pregnancy characterized by the main symptoms of hypertension, proteinuria and edema, and accompanied by headache, dizziness, nausea, vomiting, abdominal discomfort, etc. The main symptoms also include increases in creatinine, neuraminidase and sialic acid, and decreases in blood NO levels, but are not limited to these.

[0045] In the present application, zanamivir may be administered as the sole active ingredient to treat pre-eclampsia or to prepare a corresponding drug, or may be administered in combination with known or investigational drugs to treat pre-eclampsia or pre-eclampsia-related conditions or to prepare a drug combination or pharmaceutical composition, including but not limited to antihypertensive drugs, protein supplements, anti-vertigo drugs, drugs for treating cardiovascular disease, etc.

[0046] The method of administration of zanamivir by injection in the present application may be intramuscular injection, intravenous injection, intravenous drip infusion, etc., but is preferably intramuscular injection.

[0047] Depending on the dosage form and the condition, the administration frequency of zanamivir in the present application may be 1 to 7 times a week, but is preferably 1 to 4 times, and more preferably 1 to 2 times a week, and the administration duration may be 1 to 30 days, but is preferably 1 to 14 days, and more preferably 1 to 7 days.

[0048] In the present application, the dosage of zanamivir is not limited to the ranges set forth in the specification and claims, and the clinician may adjust the dosage depending on factors such as the patient's condition and the drug formulation.

[0049] The available dosage forms of zanamivir of the present application may be injections such as injection solutions and powder injections, tablets, capsules, oral liquids, oral preparations such as throat sprays or nasal sprays, and external preparations such as ointments, sprays, and patches, preferably injections and oral preparations, and particularly preferably injections.

[0050] For purposes of this application, improving pregnancy outcomes includes, but is not limited to, preventing pre-eclampsia or blood pressure related miscarriage and fetal and infant health problems.

[0051] Those skilled in the art can select suitable auxiliary agents for the drug of the present application based on their general knowledge in the pharmaceutical field. The types of auxiliary agents that can be used include, but are not limited to, solvents, cosolvents, stabilizers, dispersants, viscosity adjusters, antioxidants, sweeteners, binders, gas generating agents, etc.

[0052] In the present invention, the dosage of a neuraminidase inhibitor such as zanamivir may be 90 mg / kg to 120 mg / kg, but is preferably 120 mg / kg. Effect of the Invention

[0053] The experimental results show that zanamivir can improve the hypertension and proteinuria symptoms of preeclampsia, reduce urinary creatinine levels, reduce blood neuraminidase and sialic acid levels, and increase blood NO levels. The combination of zanamivir with hydroxyprogesterone caproate shows better preventive and therapeutic effects on preeclampsia, providing a completely new concept and method for the development of preventive and therapeutic drugs for preeclampsia. [Brief description of the drawings]

[0054] [Figure 1] Figure 1 shows the mean arterial pressure of pregnant rats in each group on day 12 of pregnancy, demonstrating that zanamivir (120 mg / kg) can significantly reduce the increase in mean arterial pressure in pregnant rats induced by L-NAME (data are mean ± standard error, N=9-22, *p<0.05). [Diagram 2] This figure shows the diastolic blood pressure of pregnant rats in each group on day 12 of pregnancy, demonstrating that zanamivir (120 mg / kg) can significantly reduce the increase in diastolic blood pressure in pregnant rats caused by L-NAME (data are mean ± standard error, N = 9-22, *p < 0.05). [Diagram 3] Systolic blood pressure diagrams of pregnant rats in each group on day 12 of pregnancy, showing that zanamivir (120 mg / kg) could significantly reduce the increase in systolic blood pressure in pregnant rats caused by L-NAME (data are mean ± standard error, N=9-22, **p<0.01). [Figure 4] This figure shows the 24-hour urinary protein of pregnant mice in each group on days 17-18 of pregnancy, demonstrating that zanamivir can significantly reduce the increase in 24-hour urinary protein in pregnant rats caused by L-NAME (data are mean ± standard error, N=5-22, **p<0.01, ***p<0.001). [Diagram 5] This figure shows the number of births in pregnant mice in each group, and indicates that zanamivir can significantly improve the reduction in the number of births in pregnant rats caused by L-NAME (data are mean ± standard error, N = 9-16, *p < 0.05). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0055] Example 1: Creation of an animal model of preeclampsia Pregnant CD-1 mice (8-10 weeks old) were randomly divided into a control group and a preeclampsia model group. On days 7-16 of the pregnancy cycle, the model group mice were subcutaneously injected with 50 mg / kg N-nitro-L-methylarginine (L-NAME) daily to induce preeclampsia. The control group mice were subcutaneously injected with the same volume of vehicle.

[0056] Example 2 Experimental Grouping TIFF0007650537000001.tif72164

[0057] Example 3 Evaluation of therapeutic effect According to literature reports, in the L-NAME-induced preeclampsia animal model, hypertension symptoms appeared 2 days after the first administration of L-NAME and continued for at least 5 days after the first administration of L-NAME. The appearance of proteinuria symptoms was relatively delayed. Therefore, in this experiment, we focused on monitoring changes in blood pressure in pregnant mice on day 12 of gestation (5 days after the first administration of L-NAME), and collected 24-hour urine samples on days 17-18 of gestation to measure the total protein level. We also recorded the number of pups born by each group of pregnant mice.

[0058] Example 4 Experimental Results The blood pressure of pregnant mice was measured on the 12th day of pregnancy (Figures 1-3). The mean arterial pressure, systolic blood pressure, and diastolic blood pressure of the pregnant model group mice were all significantly elevated compared to the pregnant control group, suggesting that this animal model successfully demonstrated the hypertensive symptoms of preeclampsia. No significant change in blood pressure was observed with 90 mg / kg zanamivir. However, administration of 120 mg / kg zanamivir significantly reduced the increase in mean arterial pressure, systolic blood pressure, and diastolic blood pressure of pregnant rats induced by L-NAME, and all were statistically significant.

[0059] The results of measuring the total protein in 24-hour urine on the 17th and 18th days of pregnancy (Figure 4) showed that the 24-hour urinary protein in the pregnant model mice was significantly elevated compared to the pregnant control group, suggesting that this animal model was successful in demonstrating the proteinuric symptoms of preeclampsia. After administration of 90 mg / kg and 120 mg / kg zanamivir, the increase in urinary protein in pregnant rats caused by L-NAME was significantly reduced, with a statistically significant difference.

[0060] In this experiment, the number of pups born by pregnant mice in each group was also recorded. As shown in Figure 5, the number of pups born by pregnant mice in the pregnancy model group was significantly reduced compared to the pregnant control group. After administration of 90 mg / kg and 120 mg / kg of zanamivir, the decrease in the number of births in pregnant mice caused by L-NAME was significantly improved, and the number of births in the 120 mg / kg group recovered to the same level as the pregnant control group, showing a statistically significant difference.

[0061] In conclusion, zanamivir can significantly improve the hypertension and proteinuria symptoms in L-NAME-induced preeclamptic pregnant rats and increase the number of live births in the pregnant rats. The results suggest that zanamivir has preventive and therapeutic effects on preeclampsia, can improve the symptoms of maternal hypertension and proteinuria, and has the potential to protect fetal development.

Claims

1. 1. Use of zanamivir in the preparation of a medicament for treating or preventing pre-eclampsia, wherein said treating or preventing pre-eclampsia is the amelioration of hypertension, proteinuria and reduced birth rate caused by N-nitro-L-arginine methyl ester.

2. The use according to claim 1, wherein the drug is in the form of an injection, an oral preparation or an external preparation.

3. The use according to claim 2, wherein the injectable preparation includes injection liquid, powder injection, the oral preparation includes tablet, capsule, oral liquid, or throat spray, and the external preparation includes ointment, spray, patch.

4. The use according to any one of claims 1 to 3, wherein zanamivir is administered by intramuscular injection, intravenous injection or intravenous infusion, administered 1 to 7 times per week, and the duration of administration is 1 to 30 days.

5. 5. The use according to claim 4, wherein zanamivir is administered 1 to 4 times a week and the duration of administration is 1 to 7 days.

6. 5. The use according to claim 4, wherein zanamivir is administered once or twice a week and the duration of administration is from 1 to 7 days.

7. A drug for treating or preventing preeclampsia, comprising zanamivir, wherein the treatment or prevention of preeclampsia is the improvement of hypertension, proteinuria and reduced birth rate caused by N-nitro-L-arginine methyl.

8. The drug according to claim 7, wherein the drug is in the form of an injection, an oral preparation or an external preparation.

9. 9. The medicament of claim 7 or 8, wherein the medicament includes instructions stating that zanamivir is administered 1-7 times per week and that the duration of administration is 1-30 days.

10. 9. The medicament of claim 7 or 8, wherein the medicament includes instructions stating that zanamivir is to be administered 1-4 times per week and that the duration of administration is 1-7 days.

11. 9. The medicament of claim 7 or 8, comprising instructions stating that zanamivir is to be administered 1-2 times per week and that the duration of administration is 1-7 days.

12. The method according to claim 7 or 8, wherein zanamivir is administered at 20 to 40 mg / day.

13. The drug of claim 7 or 8, further comprising a pharma- ceutically acceptable excipient, including, but not limited to, a solvent, a cosolvent, a stabilizer, a dispersant, a viscosity modifier, an antioxidant, a sweetener, a binder, and a gas generating agent.

14. Zanamivir may be the only active ingredient in the formulation or may further comprise other active ingredients, The use according to any one of claims 1 to 3, wherein the other active ingredients include, but are not limited to, antihypertensive drugs, protein supplements, anti-vertigo drugs, and drugs for treating cardiovascular diseases.

15. The use according to any one of claims 1 to 3, characterized in that zanamivir is administered at 90 mg / kg to 120 mg / kg.

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