阅读说明：本技术 用于预防流感病毒传播的化合物和方法 (Compounds and methods for preventing influenza virus transmission ) 是由 熨斗武志 野田阳弘 吉田立 宍户贵雄 马场薰 A·C·赫特 L·Y·Y·李 S·维尔杜 于 2020-03-26 设计创作，主要内容包括：本发明涉及用于预防流感传播的方法,其中所述方法包括对具有流感病毒感染的患者、本文称作“源头患者”施用有效量的化合物或其药学上可接受的盐,其中所述化合物具有式(I)和(II)之一。用于本发明的化合物降低源头患者的流感病毒的传染性,且由此与对照患者相比降低源头患者触发流感流行或流感大流行的风险。因此,本发明的一个方面涉及用于预防流感流行或流感大流行的方法,其中所述方法包括对具有流感病毒感染的患者(源头患者)施用有效量的化合物,其中将所述化合物施用于城市或国家人口的全部流感感染者的至少10％,且其中所述化合物具有式(I)和(II)之一或为其药学上可接受的盐。(The present invention relates to a method for preventing the spread of influenza, wherein said method comprises administering to a patient having an influenza virus infection, herein referred to as the "source patient", an effective amount of a compound, or a pharmaceutically acceptable salt thereof, wherein said compound has one of the formulae (I) and (II). The compounds for use in the present invention reduce the infectivity of influenza virus in a source patient, and thereby reduce the risk of triggering an influenza pandemic or flu pandemic in the source patient compared to a control patient. Accordingly, one aspect of the present invention relates to a method for preventing influenza pandemics or flu pandemics, wherein said method comprises administering an effective amount of a compound to a patient having an influenza virus infection (source patient), wherein said compound is administered to at least 10% of all influenza infected persons of a city or national population, and wherein said compound has one of the formulae (I) and (II) or is a pharmaceutically acceptable salt thereof.)

1. A compound for use in treating an influenza virus infection in a patient (the patient of origin), wherein the compound has one of the following formulae I and II:

or a pharmaceutically acceptable salt thereof;

and wherein the compound prevents influenza virus transmission.

2. The compound for use of claim 1, wherein the compound reduces the infectivity of influenza virus in a source patient.

3. The compound for use of claim 1 or 2, wherein the rate of transmission of influenza virus from a source patient is reduced within 1 hour to 32 hours from the 1 st administration of the compound.

4. The compound for use of any one of claims 1-3, wherein the transmission rate of influenza virus from a source patient is reduced within 2,4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, or 32 hours from the 1 st administration of the compound.

5. The compound for use according to any one of claims 1 to 4, wherein the transmission rate of influenza virus from a patient of origin receiving treatment is reduced to 70% or less, preferably to 50% or less, more preferably to 30% or less, compared to the transmission rate of influenza virus from a control patient.

6. The compound for use of claim 5, wherein a control patient has an influenza virus infection but is not administered the compound.

7. The compound for use of claim 5 or 6, wherein an anti-influenza agent other than a compound of formula (I) or (II) or a pharmaceutically acceptable salt thereof is administered to a control patient.

8. The compound for use of any one of claims 5-7, wherein the anti-influenza agent is not administered to a control patient.

9. The compound for use according to any one of claims 1 to 8, wherein transmission occurs when at least one of the contacts of the source patient receiving treatment or the control patient obtains an influenza virus infection after the person contact with the source patient receiving treatment or the control patient, respectively.

10. The compound for use of claim 9, wherein the source patient to be treated is exposed to:

(i) a person who has not developed an influenza virus infection at the time point of the first administration of the compound to the source patient; and

(ii) a person who has had personal contact with a source patient undergoing treatment during an influenza virus infection of the source patient.

11. The compound for use of claim 10(ii), wherein the contacter has had a person contact with the source patient receiving treatment within 10 days of administration of the compound to the source patient.

12. The compound for use of claim 10(ii) or 11, wherein the contacter has had human contact with the subject to be treated within a time period starting from the start of administration of the compound to the end of 5-10 days after administration of the compound.

13. The compound for use of any one of claims 9-12, wherein the contact of the control patient is:

(i) a human that has not developed an influenza virus infection at the time point of the first administration of an anti-influenza drug to a control patient; or, a human that is not infected with influenza virus at the corresponding time point in the disease process for influenza if no anti-influenza drug is administered to the control patient; and

(ii) a person who has had a person in contact with a control patient during influenza virus infection in the control patient.

14. The compound for use of claim 13(ii), wherein within 10 days from administration of the anti-influenza drug to a control patient; alternatively, if no anti-influenza drug is administered, the contacter has been in human contact with a control patient within a corresponding time frame of the disease process for influenza.

15. The compound for use of claim 13(ii) or 14, wherein the contacter has been in contact with the control patient for a period of time starting from the administration of the anti-influenza drug to the control patient, or if no anti-influenza drug is administered, starting from the corresponding point in time of the course of disease for influenza, until 5-10 days after the administration of the anti-influenza drug, or if no anti-influenza drug is administered, until the corresponding point in time of the course of disease for influenza.

16. The compound for use according to claim 10 or 13, wherein at the time points defined in (i) the contacter is influenza PCR-negative.

17. The compound for use according to any one of claims 9 to 16, wherein the human contact is a contact allowing airborne and/or direct contact transmission, preferably only airborne.

18. The compound for use according to any one of claims 9 to 17, wherein transmission from a patient of therapeutic origin occurs when influenza virus can be detected in at least one contacter of a patient of therapeutic origin.

19. The compound for use of claim 18, wherein transmission from a patient of therapeutic origin occurs if influenza virus is detectable in at least one of the contacts of the patient of therapeutic origin within 15 days from administration of the compound.

20. The compound for use of any one of claims 9-19, wherein transmission from a control patient occurs if influenza virus can be detected in at least one of the contacts of the control patient.

21. The compound for use of claim 20, wherein the anti-influenza drug is effective if within 15 days of administration of the other anti-influenza drug to a control patient; or if no anti-influenza drug is administered to the control patient, transmission from the control patient occurs when influenza virus can be detected in at least one of the contacts of the control patient within a corresponding time period of the disease process for influenza.

22. The compound for use according to any one of claims 3 to 21, wherein the transmission rate is determined by: at least one contacter of a source patient receiving treatment or a control group of patients, respectively, is tested for influenza virus infection within 10 days from administration of the compound to the source patient receiving treatment, or within 10 days from administration of another anti-influenza drug to a control patient, or within 10 days from the corresponding time point in the course of the flu illness if no anti-influenza drug is administered to a control patient.

23. The compound for use of any one of claims 1-22, wherein if an influenza virus can be detected, an influenza virus infection is present.

24. The compound for use of claim 23, wherein influenza virus is detected by PCR.

25. The compound for use of claim 23, wherein influenza virus is detected by using an influenza test kit.

26. The compound for use according to any one of claims 1 to 25, wherein transmission from a source patient receiving treatment occurs when at least one contacter of the source patient receiving treatment has an influenza virus infection with an influenza virus strain that is the same as the influenza virus strain of the source patient receiving treatment, and wherein transmission from a control patient occurs when at least one contacter of the control patient has an influenza virus infection with an influenza virus strain that is the same as the influenza virus strain of the control patient.

27. The compound for use according to any one of claims 1 to 26, wherein the transmission of influenza virus is direct contact transmission and/or airborne transmission.

28. The compound for use according to any one of claims 1 to 27, wherein the patient of origin to be treated has been in contact with at least one person of an influenza risk group or at least one person essential to social functioning after administration of the compound and during his/her influenza virus infection.

29. The compound for use of claim 28, wherein at least one human in the influenza risk group is at least one human at increased risk of acquiring an influenza virus infection or at increased risk of acquiring an influenza-related complication.

30. The compound for use of claim 29, wherein the influenza-associated complication is at least one complication selected from hospitalization, sinusitis, otitis media, bronchitis, and pneumonia.

31. The compound for use of claim 29 or 30, wherein the at least one human at increased risk of developing an influenza-associated complication is at increased risk of death from influenza virus infection.

32. The compound for use according to any one of claims 29 to 31, wherein the at least one human at increased risk of having an influenza-associated complication is an individual as follows:

(i) those suffering from chronic cardiovascular disease, chronic lung disease, chronic metabolic disease, chronic kidney disease, cardiopulmonary disease, and/or immune hypofunction; and/or

(ii) At least 65 years or less than 5 years old.

33. The compound for use according to any one of claims 29 to 32, wherein the at least one person at increased risk of acquiring an influenza virus infection is an individual contraindicated for influenza vaccination.

34. The compound for use of any one of claims 28-33, wherein the at least one person essential to social functioning is a person providing basic services, including firefighters, police officers, healthcare personnel, emergency response services personnel, military or government personnel.

35. The compound for use according to any one of claims 1 to 34, wherein the patient of origin to be treated has been in human contact with a number of people after administration of the compound and during his/her influenza virus infection.

36. The compound for use according to any one of claims 1 to 35, wherein the patient of origin is treated after administration of the compound and during his/her influenza virus infection

(i) To a care facility, educational facility, public facility, transportation facility, vehicle, aircraft and/or store, and

(ii) have had personal contact with many people.

37. The compound for use of claim 35 or 36, wherein the compound is administered at least 1 hour prior to the human contact.

38. The compound for use of any one of claims 35-37, wherein the compound is administered at least 2,4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, or 32 hours prior to the human contact.

39. The compound for use of any one of claims 1-38, wherein the compound is administered within 48 hours from the onset of influenza symptoms.

40. The compound for use according to any one of claims 1-39, wherein the compound is administered 1 time as a single treatment.

41. The compound for use according to any one of claims 1 to 40, wherein the effective amount is about 40mg for a patient of <80kg and about 80mg for a patient of ≥ 80 kg.

42. The compound for use of any one of claims 1-41, wherein the compound is administered orally.

43. The compound for use of any one of claims 1-42, wherein the source patient is at least 12 years of age.

44. The compound for use according to any one of claims 1 to 43, wherein the patient of origin receiving the treatment has a reduced risk of triggering an influenza pandemic or flu pandemic compared to a control patient.

45. The compound for use of any one of claims 1-44, wherein the influenza virus is an influenza A virus or an influenza B virus.

46. The compound for use of any one of claims 1-45, wherein the influenza virus is a pandemic influenza virus strain or a pandemic influenza virus strain.

47. The compound for use of any one of claims 1-46, wherein the influenza virus is antigenically different as compared to the parent influenza virus strain as a result of antigenic drift and/or antigenic shift.

48. The compound for use of any one of claims 1-47, wherein the influenza strain is a recycled virus that has caused a pandemic or pandemic in the past.

49. The compound for use of any one of claims 1-48, wherein the influenza strain does not carry the I38X mutation, including the I38T mutation.

50. A compound for use in treating a patient having an influenza virus infection (source patient), wherein the compound is administered to at least 10% of all influenza infected persons of an urban or national population, wherein the compound prevents influenza epidemics or influenza pandemics, and wherein the compound has one of the following formulae I and II:

or a pharmaceutically acceptable salt thereof.

51. The compound for use of claim 50, wherein the compound is for preventing influenza epidemics and wherein at least 10% of all influenza infected persons of a city or national population are treated with the compound.

52. The compound for use of claim 50, wherein the compound is for preventing influenza pandemics, and wherein at least 25% of all influenza infected persons of the national population are treated with the compound.