1. A radioactive metal complex based on bispidine and the derivatives thereof as chelating agent having the following general formula (I)
in which
A and B are independently of one another H, \u2014OR1, \u2014SR1, \u2014NHR1, \u2014OC(O)R1, \u2014NHC(O)R1 or a straight-chain or branched-chain (C1-8) alkyl radical, or A and B together are \u2550O or \u2550S, where R1 is hydrogen, a straight-chain or branched-chain (C1-8) alkyl radical, a substituted or unsubstituted (C6-10) aryl radical,
D is in each case a carboxyl group or a derivative derived therefrom and selected from esters, amides and peptides,
X, Y and Z are independently of one another an unsubstituted or substituted heterocycle selected from pyridine, pyrimidine, pyrazine, thiophene, furan, pyrazole, imidazole, thiazole, quinoline, quinazoline and quinoxaline, where the substituents may have been selected from straight-chain or branched-chain (C1-8) alkyl radicals, halogen, straight-chain or branched-chain (C1-8) alkoxy radicals, sulfonate, carboxylate, nitro, cyano, hydroxy, benzyl or phenyl,
the radical R in the respective alkylene bridge is independently of one another hydrogen, hydroxy, a straight-chain or branched-chain (C1-8) alkyl radical, a straight-chain or branched-chain (C1-8) alkoxy radical, \u2014OC(O)R1 or \u2014NHC(O)R1, where the radical R1 is as defined above,
M* is a radioactive metal, and
m and n is in each case an integer between 1 and 5.
2. The radioactive metal complex as claimed in claim 1, wherein, in formula (I), A and B are independently of one another H, \u2014OR1, \u2014OC(O)R1 or \u2014NHC(O)R1, or A and B are together \u2550O,
D is in each case a carboxyl group or an ester derivative derived therefrom,
X, Y and Z are in each case an unsubstituted or substituted pyridine, and
the radical R in the respective alkylene bridge is independently of one another hydrogen, hydroxy, a straight-chain or branched-chain (C1-8) alkyl radical, a straight-chain or branched-chain (C1-8) alkoxy radical, \u2014OC(O)R1 or \u2014NHC(O)R1, where the radical R1 is as defined above.
3. The radioactive metal complex as claimed in claim 1, wherein, in formula (I), A and B are respectively H and OH,
D is in each case a \u2014COOH group or a \u2014COOMe group,
X, Y and Z are in each case 2-pyridinyl, and
the radical R in the respective alkylene bridge is in each case hydrogen,
and m and n are each 1.
4. The radioactive metal complex as claimed in claim 1, wherein the radioactive metal M* is a nuclide of copper, of rare earths, Tc, In, Ga, Y or Re.
5. The radioactive metal complex as claimed in claim 1, wherein the radioactive metal M* is 64Cu or 188Re.
6. A method of nuclear medical diagnosis, comprising administering to a living body the radioactive metal complex as claimed in claim 1.
7. A method of internal radio nuclide therapy, comprising administering to a living body the radioactive metal complex as claimed in claim 1.
8. A method for preparing the radioactive metal complexes based on bispidine and the derivatives thereof as chelating agents as claimed in claim 1, in which a radioactive metal is mixed with the bispidine or derivative thereof in an aqueous or aqueous-organic solution and brought to a temperature between 20 and 50\xb0 C. and kept at this temperature for one hour.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A sleep awaking system comprising:
a sign parameter collecting module configured to collecting a sign parameter of a human body;
a time determining module configured to determining whether the present time is a REM determining time;
a REM determining module configured to obtaining the sign parameter and determining whether the human body is in a REM stage according to the sign parameter in a REM determining period when the time determining module determines that the present time is the REM determining time;
an awaking module configured to awaking the human body after a pre-awaking period when the REM determining module determines that the human body is in the REM stage, and causing the human body to enter the REM stage within the pre-awaking period and awaking the human body after the pre-awaking period when the REM determining module determines that the human body is not in the REM stage,
wherein the REM determining period and the pre-awaking period pass in turn from the REM determining time to the awaking time.
2. The sleep awaking system according to claim 1, wherein the sign parameter collecting module comprises an acceleration collecting unit configured to collecting acceleration signals of body movement.
3. The sleep awaking system according to claim 1, wherein the REM determining module comprises:
a sleepwake determining unit configured to obtaining acceleration signals of respective times within the REM determining period when the time determining module determines that the present time is the REM determining time, calculating the total variation of the acceleration signals within the REM determining period, and comparing the total variation of the acceleration signals with a threshold for the total variation of the acceleration signals within the REM determining period, determining that the human body is in a sleep state when the total variation of the acceleration signals is smaller than or equal to the threshold for the total variation of the acceleration signals, and determining that the human body is in a wake state when the total variation of the acceleration signals is larger than the threshold for the total variation of the acceleration signals; and
a REM determining unit configured to calculating variations of acceleration signals at adjacent times within the REM determining period, when the sleepwake determining unit determines that the human body is in the sleep state, comparing the variations of the acceleration signals with a threshold for the variations of the acceleration signals one by one, and determining whether variation of the acceleration signals is periodic, determining that the human body is in the REM stage when at least one variation of the acceleration signals is larger than the threshold for the variations of the acceleration signals at adjacent times andor the variation of the acceleration signals is not periodic, and determining that the human body is not in the REM stage when all the variations of the acceleration signals are smaller than or equal to the threshold for the variations of the acceleration signals at adjacent times and the variation of the acceleration signals is periodic.
4. The sleep awaking system according to claim 3, wherein the sign parameter collecting module further comprises a heart rate collecting unit configured to collecting heart rate signals;
the sleepwake determining unit of the REM determining module is configured to obtain heart rate signals of respective times within the REM determining period when the time determining module determines that the present time is the REM determining time, calculate the average of the heart rate signals within the REM determining period, compare the average of the heart rate signals with a threshold for the average of the heart rate signals within the REM determining period, determine that the human body is in the sleep state when the average of the heart rate signals is smaller than or equal to the threshold for the average of the heart rate signals and the total variation of the acceleration signals is smaller than or equal to the threshold for the total variation of the acceleration signals, and determine that the human body is in a wake state when the average of the heart rate signals is larger than the threshold for the average of the heart rate signals andor the total variation of the acceleration signals is larger than the threshold for the total variation of the acceleration signals; and
the REM determining unit of the REM determining module is configured to calculate variations of the heart rate signals at adjacent times within the REM determining period when the sleepwake determining unit determines that the human body is in the seep state, compare the variations of the heart rate signals with a threshold for the variations of the heart rate signals at adjacent times one by one, and determine whether variation of the heart rate signals is periodic, determine the human body is in the REM stage when any one or more of the determination results of the four determinations that at least one variation of the heart rate signals is larger than the threshold for the variations of the heart rate signals at adjacent times, that the variation of the heart rate signals is not periodic, that at least one variation of the acceleration signals is larger than the threshold for the variations of the acceleration signals at adjacent times and that the variation of the acceleration signals is not periodic is true, and determine that the human body is not in the REM stage when all the variations of the heart rate signals are smaller than or equal to the threshold for the variations of the heart rate signals at adjacent times, all the variations of the acceleration signals are smaller than or equal to the threshold for the variations of the acceleration signals at adjacent times, and the variation of the heart rate signals and the variation of the acceleration signals are both periodic.
5. The sleep awaking system according to claim 3, wherein the sign parameter collecting module further comprises a body temperature collecting unit configured to collecting body temperature signals; and
the REM determining unit of the REM determining module is configured to obtain a variation curve of the body temperature signals with respect to time within the REM determining period when the time determining module determines that the present time is the REM determining time, calculate a difference degree between the variation curve of the body temperature signals with respect to time and the ideal variation curve of the body temperature signals of the human body in the REM stage with respective to time, determine the human body is in the REM stage when any one or more of the determination results of the five determinations that the difference degree is smaller than or equal to a threshold for the difference degree, that at least one variation of the acceleration signals is larger than the threshold for the variations of the acceleration signals at adjacent times, that the variation of the acceleration signals is not periodic, that at least one variation of the heart rate signals is larger than the threshold for the variations of the heart rate signals at adjacent times and that the variation of the heart rate signals is not periodic is true, and determine that the human body is not in the REM stage when the difference degree is larger than the threshold for the difference degree, all the variations of the acceleration signals are smaller than or equal to the threshold for the variations of the acceleration signals at adjacent times, all the variations of the heart rate signals are smaller than or equal to the threshold for the variations of the heart rate signals at adjacent times, and the variation of the heart rate signals and the variation of the acceleration signals are both periodic.
6. The sleep awaking system according to claim 3, wherein an awaking buffering period is included after the REM determining period and the pre-awaking period pass in turn from the REM determining time to the awaking time, and the time length from the REM determining time to the awaking time is equal to the sum of the REM determining period, the pre-awaking period and the awaking buffering period.
7. The sleep awaking system according to claim 6, wherein the awaking module comprises:
a white light emitting unit configured to emitting white light changing gradually from weak to strong within the awaking buffering period after the pre-awaking period until the human body is awaked or the awaking buffering period is over and stopping emitting the white light changing gradually from weak to strong then;
a blue light emitting unit configured to emitting blue light changing gradually from weak to strong within the pre-awaking period when the REM determining module determines that the human body is not in the REM stage to cause the human body to enter the REM stage until the pre-awaking period is over, and stopping emitting the blue light changing gradually from weak to strong then;
a sound generating unit configured to generating a sound to awake the human body when the human body is not awaked at the end of the awaking buffering period.
8. The sleep awaking system according to claim 7, wherein the sleepwake determining unit of the REM determining module is also configured to determine whether the human body is in the sleep state or the wake state within the awaking buffering period, and trigger the white light emitting unit to stop emitting the white light changing gradually from weak to strong when it is determined that the human body is in the wake state.
9. The sleep awaking system according to claim 6, wherein the time length of the REM determining period is 8 minutes\u02dc12 minutes, the time length of the pre-awaking period is 15 minutes\u02dc25 minutes, and the time length of the awaking buffering period is 10 minutes\u02dc20 minutes.
10. The sleep awaking system according to claim 1, wherein the time length from the REM determining time to the awaking time is equal to the sum of the REM determining period and the pre-awaking period.
11. A sleep awaking method comprising:
a step S1 of collecting a sign parameter of a human body;
a step S2 of determining whether the present time is a REM determining time, and entering a step S3 if yes;
the step S3 of obtaining the sign parameter, determining whether the human body is in a REM stage according to the sign parameter within the REM determining period, entering a step S4 if yes, and entering a step S5 if no;
the step S4 of awaking the human body after a pre-awaking period;
the step S5 of causing the human body to enter the REM stage within the pre-awaking period, and awaking the human body after the pre-awaking period,
wherein the REM determining period and the pre-awaking period pass in turn from the REM determining time to the awaking time.
12. The sleep awaking method according to claim 11, wherein the step S1 comprises collecting acceleration signals of body movement.
13. The sleep awaking method according to claim 12, wherein the step S3 comprises:
a step S31 of obtaining acceleration signals of respective times within the REM determining period, calculating the total variation of the acceleration signals within the REM determining period, comparing the total variation of the acceleration signals with a threshold for the total variation of the acceleration signals within the REM determining period, determining that the human body is in a sleep state and entering a step S32 if the total variation of the acceleration signals is smaller than or equal to the threshold for the total variation of the acceleration signals, and determining that the human body is in a wake state if the total variation of the acceleration signals is larger than the threshold for the total variation of the acceleration signals; and
the step S32 of calculating variations of acceleration signals at adjacent times within the REM determining period, comparing the variations of the acceleration signals with a threshold for the variations of the acceleration signals at adjacent times one by one, determining whether variation of the acceleration signals is periodic, determining that the human body is in the REM stage and entering the step S4 when at least one variation of the acceleration signals is larger than the threshold for the variations of the acceleration signals at adjacent times andor the variation of the acceleration signals is not periodic, and determining that the human body is not in the REM stage and entering the step S5 when all the variations of the acceleration signals are smaller than or equal to the threshold for the variations of the acceleration signals at adjacent times and the variation of the acceleration signals is periodic.
14. The sleep awaking method according to claim 13, wherein the step S1 further comprises collecting heart rate signals;
the step S31 comprises: obtaining heart rate signals of respective times within the REM determining period, calculating the average of the heart rate signals within the REM determining period, comparing the average of the heart rate signals with a threshold for the average of the heart rate signals within the REM determining period, determining that the human body is in the sleep state and entering the step S32 if the average of the heart rate signals is smaller than or equal to the threshold for the average of the heart rate signals and the total variation of the acceleration signals is smaller than or equal to the threshold for the total variation of the acceleration signals, and determine that the human body is in a wake state if the average of the heart rate signals is larger than the threshold for the average of the heart rate signals andor the total variation of the acceleration signals is larger than the threshold for the total variation of the acceleration signals; and
the step S32 comprises: calculating variations of the heart rate signals at adjacent times within the REM determining period, comparing the variations of the heart rate signals with a threshold for the variations of the heart rate signals at adjacent times one by one, determining whether variation of the heart rate signals is periodic, determining that the human body is in the REM stage and entering the step S4 if any one or more of the determination results of the four determinations that at least one variation of the heart rate signals is larger than the threshold for the variations of the heart rate signals at adjacent times, that the variation of the heart rate signals is not periodic, that at least one variation of the acceleration signals is larger than the threshold for the variations of the acceleration signals at adjacent times and that the variation of the acceleration signals is not periodic is true, and determining that the human body is not in the REM stage and entering the step S5 if all the variations of the heart rate signals are smaller than or equal to the threshold for the variations of the heart rate signals at adjacent times, all the variations of the acceleration signals are smaller than or equal to the threshold for the variations of the acceleration signals at adjacent times, and the variation of the heart rate signals and the variation of the acceleration signals are both periodic.
15. The sleep awaking method according to claim 14, wherein the step S1 further comprises collecting body temperature signals; and
the step S32 comprises: obtaining a variation curve of the body temperature signals with respect to time within the REM determining period, calculating a difference degree between the variation curve of the body temperature signals with respect to time and the ideal variation curve of the body temperature signals of the human body in the REM stage with respective to time, determining the human body is in the REM stage and entering the step S4 if any one or more of the determination results of the five determinations that the difference degree is smaller than or equal to a threshold for the difference degree, that at least one variation of the acceleration signals is larger than the threshold for the variations of the acceleration signals at adjacent times, that the variation of the acceleration signals is not periodic, that at least one variation of the heart rate signals is larger than the threshold for the variations of the heart rate signals at adjacent times and that the variation of the heart rate signals is not periodic is true, and determine that the human body is not in the REM stage and entering the step S5 if the difference degree is larger than the threshold for the difference degree, all the variations of the acceleration signals are smaller than or equal to the threshold for the variations of the acceleration signals at adjacent times, all the variations of the heart rate signals are smaller than or equal to the threshold for the variations of the heart rate signals at adjacent times, and the variation of the heart rate signals and the variation of the acceleration signals are both periodic.
16. The sleep awaking method according to claim 13, wherein an awaking buffering period is included after the REM determining period and the pre-awaking period pass in turn from the REM determining time to the awaking time, the time length from the REM determining time to the awaking time is equal to the sum of the REM determining period, the pre-awaking period and the awaking buffering period.
17. The sleep awaking method according to claim 16, wherein the step S4 comprises: emitting white light changing gradually from weak to strong within the awaking buffering period after the pre-awaking period until the human body is awaked or the awaking buffering period is over and stopping emitting the white light changing gradually from weak to strong then; and generating a sound to awake the human body if the human body is not awaked at the end of the awaking buffering period;
the step S5 comprises: emitting blue light changing gradually from weak to strong within the pre-awaking period to cause the human body to enter the REM stage until the pre-awaking period is over, and stopping emitting the blue light changing gradually from weak to strong then; emitting white light changing gradually from weak to strong within the awaking buffering period until the human body is awaked or the awaking buffering period is over and stopping emitting the white light changing gradually from weak to strong then; and generating a sound to awake the human body if the human body is not awaked at the end of the awaking buffering period.
18. The sleep awaking method according to claim 17, wherein the step S4 further comprises: determining whether the human body is in the sleep state or the wake state within the awaking buffering period, and stopping emitting the white light changing gradually from weak to strong when it is determined that the human body is in the wake state.
19. The sleep awaking method according to claim 16, wherein the time length of the REM determining period is 8 minutes\u02dc12 minutes, the time length of the pre-awaking period is 15 minutes\u02dc25 minutes, and the time length of the awaking buffering period is 10 minutes\u02dc20 minutes.
20. The sleep awaking system according to claim 11, wherein the time length from the REM determining time to the awaking time is equal to the sum of the REM determining period and the pre-awaking period.