CN116687921A - Application of Sha Kuba triptan in preparation of neurotoxicity and cognitive dysfunction medicines - Google Patents
Application of Sha Kuba triptan in preparation of neurotoxicity and cognitive dysfunction medicines Download PDFInfo
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- CN116687921A CN116687921A CN202310709424.4A CN202310709424A CN116687921A CN 116687921 A CN116687921 A CN 116687921A CN 202310709424 A CN202310709424 A CN 202310709424A CN 116687921 A CN116687921 A CN 116687921A
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- valsartan
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- 239000003814 drug Substances 0.000 title claims abstract description 35
- 208000010877 cognitive disease Diseases 0.000 title claims abstract description 28
- 206010029350 Neurotoxicity Diseases 0.000 title claims abstract description 21
- 206010044221 Toxic encephalopathy Diseases 0.000 title claims abstract description 21
- 230000007135 neurotoxicity Effects 0.000 title claims abstract description 21
- 231100000228 neurotoxicity Toxicity 0.000 title claims abstract description 21
- ZISSAWUMDACLOM-UHFFFAOYSA-N triptane Chemical compound CC(C)C(C)(C)C ZISSAWUMDACLOM-UHFFFAOYSA-N 0.000 title claims description 32
- 229940079593 drug Drugs 0.000 title abstract description 17
- 239000004072 C09CA03 - Valsartan Substances 0.000 claims abstract description 23
- 239000000126 substance Substances 0.000 claims abstract description 23
- 229960004699 valsartan Drugs 0.000 claims abstract description 23
- SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 claims abstract description 17
- 239000000178 monomer Substances 0.000 claims abstract description 10
- 229940001470 psychoactive drug Drugs 0.000 claims abstract description 8
- 239000004089 psychotropic agent Substances 0.000 claims abstract description 8
- 150000003839 salts Chemical class 0.000 claims abstract description 8
- -1 valsartan compound Chemical class 0.000 claims abstract description 7
- 150000004104 valsartan derivatives Chemical class 0.000 claims abstract description 3
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 2
- 159000000000 sodium salts Chemical group 0.000 claims description 2
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- 230000000694 effects Effects 0.000 abstract description 6
- 208000028698 Cognitive impairment Diseases 0.000 abstract description 3
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- 229960001252 methamphetamine Drugs 0.000 description 32
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- 238000001514 detection method Methods 0.000 description 10
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- 230000001225 therapeutic effect Effects 0.000 description 7
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- 230000001988 toxicity Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical group C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
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- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 2
- 229940083542 sodium Drugs 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 2
- 230000031836 visual learning Effects 0.000 description 2
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- HRYZPBSOAMTFEL-UHFFFAOYSA-N 1,3-diazinane-2,4,6-trione;sodium Chemical compound [Na].O=C1CC(=O)NC(=O)N1 HRYZPBSOAMTFEL-UHFFFAOYSA-N 0.000 description 1
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- 102000005862 Angiotensin II Human genes 0.000 description 1
- 102000008873 Angiotensin II receptor Human genes 0.000 description 1
- 108050000824 Angiotensin II receptor Proteins 0.000 description 1
- 101800000733 Angiotensin-2 Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000011597 CGF1 Diseases 0.000 description 1
- 229940122586 Enkephalinase inhibitor Drugs 0.000 description 1
- 241001539473 Euphoria Species 0.000 description 1
- 206010015535 Euphoric mood Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 1
- NQRAWXHLZGWKRS-FTBISJDPSA-N [Na].C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NNN=N1 Chemical compound [Na].C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NNN=N1 NQRAWXHLZGWKRS-FTBISJDPSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
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- 229940025084 amphetamine Drugs 0.000 description 1
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- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- DCSUBABJRXZOMT-IRLDBZIGSA-N cisapride Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=CC(N)=C(Cl)C=2)OC)OC)N1CCCOC1=CC=C(F)C=C1 DCSUBABJRXZOMT-IRLDBZIGSA-N 0.000 description 1
- 229960005132 cisapride Drugs 0.000 description 1
- DCSUBABJRXZOMT-UHFFFAOYSA-N cisapride Natural products C1CC(NC(=O)C=2C(=CC(N)=C(Cl)C=2)OC)C(OC)CN1CCCOC1=CC=C(F)C=C1 DCSUBABJRXZOMT-UHFFFAOYSA-N 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 229940000425 combination drug Drugs 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000002792 enkephalinase inhibitor Substances 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 208000029790 metamphetamine dependence Diseases 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000004039 social cognition Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000006886 spatial memory Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 229960005294 triamcinolone Drugs 0.000 description 1
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
- 229960002117 triamcinolone acetonide Drugs 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Emergency Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The application relates to an application of Sha Kuba valsartan substances in preparing neurotoxicity and cognitive impairment medicines, wherein the Sha Kuba valsartan substances comprise at least one of Sha Kuba koji monomers, sha Kuba koji derivatives, sha Kuba koji pharmacologically acceptable salts, valsartan monomers, valsartan derivatives, valsartan pharmacologically acceptable salts and Sha Kuba valsartan compound medicines. Compared with the prior art, the Sha Kuba trovaptan substance has remarkable effect in treating cognitive impairment caused by psychotropic drugs.
Description
Technical Field
The application belongs to the technical field of biological medicines, relates to a new application of Sha Kuba trovaptan substances, and in particular relates to an application of Sha Kuba trovaptan substances in preparing medicines for treating neurotoxicity and cognitive impairment caused by psychotropic medicines.
Background
Psychotropic drug use disorders can lead to neurotoxicity, which in turn can lead to impaired cognitive function, including spatial learning and memory, executive abilities, social cognition, language/language fluency, attention, and the like.
Taking methamphetamine (METH, commonly known as ice toxin) as an amphetamine-type stimulant, the methamphetamine-type stimulant can produce euphoria and suppress appetite after use. Long term use may cause neurotoxicity and cognitive dysfunction.
Sha Kuba triptan is a compound drug consisting of an enkephalinase inhibitor (Sha Kuba koji) and an angiotensin receptor inhibitor (valsartan), and is mainly used for treating heart failure and hypertension in temporary production. For example, [ Yes, et al front Cell Dev Biol ] and [ Menndez JT. Card Fail Rev ] reported a significant therapeutic effect of Sha Kuba triamcinolone on heart failure. [ Xu X, et al food Chem Toxicol ] reports the correlation of angiotensin II with methamphetamine addiction in pathogenesis.
The application patent No. 202211034360.4 of the inventor (Sha Kuba) discloses the application of Sha Kuba triptan substances in preparing medicament addiction and re-absorption medicaments (the application of the patent No. CN 115317478B) and proves that Sha Kuba triptan can treat medicament addiction and re-absorption after administration, and the medicament has no addiction.
While Sha Kuba cisapride has not been studied in psychology-induced neurotoxicity and cognitive dysfunction.
Disclosure of Invention
Aiming at the current state of the art, the technical problem to be solved by the application is to provide the application of the sarcandesartan cilexetil in preparing the medicines for treating the neurotoxicity and the cognitive disorder caused by the psychotropic medicines.
The technical scheme adopted for solving the technical problems is as follows: the application of Sha Kuba triptan substances in preparing neurotoxicity and cognitive disorder medicaments comprises Sha Kuba triptan substances including at least one of Sha Kuba triptan monomers, sha Kuba triptan derivatives, sha Kuba triptan pharmacologically acceptable salts, valsartan monomers, valsartan derivatives, valsartan pharmacologically acceptable salts and Sha Kuba triptan compound medicaments.
The chemical formula of the Sha Kuba valsartan compound medicine is as follows, wherein the left side is Sha Kuba Qu Shanti, the right side is valsartan monomer, and the valsartan compound medicine and the valsartan monomer form Sha Kuba valsartan compound medicine:
preferably, the derivative is an acetyl or an esterified compound.
Preferably, the pharmacologically acceptable salt is a sodium or potassium salt. Wherein the chemical formula of the sodium salt is as follows:
preferably, the effective dose of the Sha Kuba valsartan substance on mice is 20-200mg/kg/d.
More preferably, the effective dose of Sha Kuba trovasartan on mice is 60mg/kg/d.
In each of the above regimens, preferably, the neurotoxicity and cognitive disorder is caused by a psychotropic drug, and the psychotropic drug comprises an opioid, barbituric sodium, benzodiazepine or amphetamine drug.
Compared with the prior art, the application has the advantages that:
1. aiming at the current situation of lack of medicines for clinically treating neurotoxicity and cognitive dysfunction caused by psychotropic medicines, the application provides a novel application of Sha Kuba trovaptan substances in preparing medicines for treating neurotoxicity and cognitive dysfunction caused by psychotropic medicines.
2. The application provides Sha Kuba troxartan substances which obviously improve neurotoxicity and cognitive dysfunction caused by psychotropic drugs after administration, and proves that Sha Kuba troxartan substances have obvious effects in treating the cognitive dysfunction caused by the psychotropic drugs.
3. Sha Kuba the administration of sartan does not have any adverse effect.
Drawings
FIG. 1 is a model of methamphetamine-impaired cognition in example 1 of the present application;
FIG. 2 is a model of methamphetamine-impaired cognition in example 1 of the present application;
fig. 3 is a graph showing the therapeutic effect of Sha Kuba troxartan cilexetil complex in example 2 of the application on cognitive disorders caused by methamphetamine;
fig. 4 is a graph showing the therapeutic effect of Sha Kuba troxartan cilexetil complex in example 2 of the application on cognitive disorders caused by methamphetamine;
FIG. 5 is a graph showing the therapeutic effect of Sha Kuba of the compound pharmaceutical composition of the present application on neurotoxicity caused by neuroblastoma cells after methamphetamine treatment.
Detailed Description
The application is described in further detail below with reference to the embodiments of the drawings.
The methamphetamine used in the embodiment of the application is a standard substance and comes from the Ningbo public security bureau of forbidden teams. Sha Kuba the sartan compound medicine is from Shanghai ruihui chemical industry.
Example 1: experimental modeling of cognitive dysfunction caused by methamphetamine
The new object identification is an experimental model for evaluating cognitive memory, and the Y maze is a model for evaluating spatial learning memory capacity, and the cognitive dysfunction caused by the mental medicines is evaluated by the two models.
Male mice 16 (variety C57BL/6J,6-8 weeks old, body weight 22-25 g) were housed in SPF-class animal houses, and after 1 week of adaptive feeding, they were randomly divided into physiological saline groups (8), methamphetamine groups (8).
The new object identification and Y maze test were performed as follows:
methamphetamine (2.5 mg/kg/day) was administered by intraperitoneal injection in the methamphetamine group from day 1 to day 5, and physiological saline was administered by intraperitoneal injection in the physiological saline group. On day 6, two identical objects a were placed in the apparatus, allowing the mice to explore for 10min. The time the mice remained on each object was recorded by a camera (AniLab software instruments limited, ningbo, china). On day 7, one of the two identical objects a in the device was replaced with object B, which was not used for object a, and the mice were allowed to explore for 10min, recording the time spent on each object. During exploration, each mouse is independently explored in the equipment, and after the previous mouse is explored and before the next mouse is explored, the explored object and the equipment are wiped by alcohol to eliminate odor clues. The main outcome index is the preference index and exploration time for the new object. Preference index = (new object detection time-old object detection time)/(new object detection time + old object detection time) ×100%. Wherein, the new object in the formula refers to an object B, the old object refers to an object A, and the detection time refers to the time when the mouse touches the object.
The Y-maze consisted of three equal arms (50 cm x 18cm x 35 cm) and recorded three arms, arm a, arm B, arm C, respectively, arranged in either clockwise or counterclockwise directions, each arm at an angle of 120 degrees to a movable partition in the center (AniLab software instruments ltd, ningbo, china). On day 8, mice were placed on one arm (as the starting arm) and allowed free exploration of the three open arms within 5 minutes. On day 9, the camera recorded the number of consecutive mouse entries into the three arms. Sequential entries (e.g., arms ABC, BCA, CAB) arranged clockwise or counterclockwise are active and alternating arms BCB, AAC, BAB are inactive. The main outcome index is the alternating percentage, calculated as follows: percentage alternation = number of effective alternations/(total number of entries-2) ×100%. When the mice are explored on days 8 and 9, each mouse is explored in the Y-shaped maze independently, and after the previous mouse is explored and before the next mouse is explored, alcohol is used for wiping the explored Y-shaped maze to eliminate odor clues.
As shown in fig. 1 and 2, in the new object identification experiment, the preference index of methamphetamine group to new objects was significantly lower than that of saline group; also in the Y maze experiment, the effective alternating percentage of methamphetamine group was significantly lower than that of saline group. Indicating that the cognitive function of methamphetamine group was impaired. Wherein "normal saline" in fig. 1 and 2 refers to a normal saline group, and "methamphetamine" refers to a methamphetamine group.
Example 2: sha Kuba effects of treatment on cognitive disorders caused by the combination drug of sartan and methamphetamine the application adopts the following method to establish a cognitive disorder model of mice:
male mice 21 (variety C57BL/6J,6-8 weeks old, body weight 22-25 g) were housed in SPF-class animal houses and after 1 week of adaptive feeding were randomly divided into methamphetamine+ Sha Kuba triamcinolone acetonide group (6), physiological saline group (7) and methamphetamine group (8).
The new object identification and Y maze test were performed as follows:
the methamphetamine + Sha Kuba triptan group was infused with stomach Sha Kuba of the triton (60 mg/kg/day), the normal saline group was administered with normal saline, the methamphetamine + Sha Kuba triptan group was pre-treated with Sha Kuba of the triton on day 10 to day 14, the methamphetamine (2.5 mg/kg/day) was administered by intraperitoneal injection after 1 hour, the normal saline group was first administered with normal saline infusion treatment, the normal saline group was administered by intraperitoneal injection after 1 hour, and the methamphetamine group was administered by intraperitoneal injection (2.5 mg/kg/day). On day 15, mice were allowed to freely move in the object-free device for 10min. On day 16, two identical objects a were placed in the apparatus, allowing the mice to explore for 10min. The time the mice remained on each object was recorded by a camera (AniLab software instruments limited, ningbo, china). On day 17, one of the two identical objects a in the device was replaced with object B, which was not used for object a, and the mice were allowed to explore for 10min, recording the time spent on each object. During exploration, each mouse is independently explored in the equipment, and after the previous mouse is explored and before the next mouse is explored, the explored object and the equipment are wiped by alcohol to eliminate odor clues. The main outcome index is the preference index and exploration time for the new object. Preference index = (new object detection time-old object detection time)/(new object detection time + old object detection time) ×100%. Wherein, the new object in the formula refers to an object B, the old object refers to an object A, and the detection time refers to the time when the mouse touches the object.
The Y-maze consisted of three equal arms (50 cm x 18cm x 35 cm) and recorded three arms, arm a, arm B, arm C, respectively, arranged in either clockwise or counterclockwise directions, each arm at an angle of 120 degrees to a movable partition in the center (AniLab software instruments ltd, ningbo, china). On day 18, mice were placed on one arm (the starting arm) and allowed free exploration of the three open arms within 5 minutes. On day 19, the camera recorded the number of consecutive mouse entries into the three arms. Sequential entries (e.g., arms ABC, BCA, CAB) arranged clockwise or counterclockwise are active and alternating arms BCB, AAC, BAB are inactive. The main outcome index is the alternating percentage, calculated as follows: percentage alternation = number of effective alternations/(total number of entries-2) ×100%. On days 18 and 19, each mouse explored independently in the Y-shaped maze, and after the previous mouse explored and before the next mouse explored, the explored Y-shaped maze was wiped with alcohol to eliminate odor clues.
As shown in fig. 3 and 4, the preference index and the effective alternation ratio for the new object are different between the methamphetamine group and the methamphetamine+ Sha Kuba troxartan group, which indicates that 60 mg/kg/day of gastric lavage Sha Kuba troxartan has a therapeutic effect on cognitive dysfunction caused by methamphetamine. In fig. 3 and 4, "normal saline+normal saline" refers to a normal saline group, "methamphetamine+ Sha Kuba triamcinolone acetonide" refers to a methamphetamine+ Sha Kuba triamcinolone acetonide group, and "normal saline+methamphetamine" refers to a methamphetamine group.
Example 3: sha Kuba therapeutic effects of sartan composite drug on toxicity of methamphetamine to human neuroblastoma cell line SH-SY5Y
Human neuroblastoma cells were cultured in an F12 culture medium containing 10% fetal bovine serum and 1% penicillin-streptomycin, and cultured in a carbon dioxide incubator at a constant temperature of 37 degrees celsius, and the cell growth state was observed every two days, and the medium was changed, and the cell density was about 75%, and was passaged for later experiments.
The protective effect of Sha Kuba trovaptan on toxicity of methamphetamine on neuroblastoma cells was investigated as follows:
the therapeutic concentration of Sha Kuba of valsartan on methamphetamine treated neuroblastoma cells was measured using the CCK8 kit from APExBIO company, usa. Neuroblastoma cells were seeded in 96-well plates, pretreated with different concentrations of Sha Kuba troxatan for 30 min, and then pretreated with 2.5mM of METH for 24h. CCK8 solution was prepared at 1:9 was diluted with medium to a mixture, 100ul of the mixture was added to each well, and incubated at 37℃for 2-3 hours. The absorbance of each well at λ=450 nm was measured with a microplate reader.
As shown in fig. 5, sha Kuba valsartan can reduce toxicity of neuroblastoma cells caused by methamphetamine treatment.
In the application, the effects of the above embodiments can be achieved when the effective dose of the Sha Kuba valsartan compound medicine is 20mg/kg/d, 200mg/kg/d or other doses between the two. Meanwhile, experiments show that at least one of Sha Kuba yeast monomers, sha Kuba yeast acetyl or esterified substances, sha Kuba yeast sodium or potassium salts, valsartan monomers, valsartan acetyl or esterified substances and valsartan sodium or potassium salts can also achieve the effects of the above embodiments.
Claims (6)
1. The application of Sha Kuba triptan substances in preparing neurotoxicity and cognitive disorder medicaments comprises Sha Kuba triptan substances including at least one of Sha Kuba triptan monomers, sha Kuba triptan derivatives, sha Kuba triptan pharmacologically acceptable salts, valsartan monomers, valsartan derivatives, valsartan pharmacologically acceptable salts and Sha Kuba triptan compound medicaments.
2. The use of Sha Kuba of a trovaptan according to claim 1, for the preparation of a medicament for the treatment of neurotoxicity and cognitive disorders, characterized in that: the derivative is an acetyl or esterified substance.
3. The use of Sha Kuba of a trovaptan according to claim 1, for the preparation of a medicament for the treatment of neurotoxicity and cognitive disorders, characterized in that: the pharmacologically acceptable salt is a sodium salt or a potassium salt.
4. The use of Sha Kuba of a trovaptan according to claim 1, for the preparation of a medicament for the treatment of neurotoxicity and cognitive disorders, characterized in that: the effective dose of the Sha Kuba valsartan substance on mice is 20-200mg/kg/d.
5. The use of Sha Kuba of a trovaptan according to claim 4, for the preparation of a medicament for neurotoxicity and cognitive disorders, characterized in that: the effective dose of the Sha Kuba valsartan substance on mice is 60mg/kg/d.
6. The use of Sha Kuba trovaptan according to any of claims 1 to 5, for the preparation of a medicament for the treatment of neurotoxicity and cognitive disorders, characterized in that: the neurotoxicity and cognitive disorder is caused by psychotropic drugs, and the psychotropic drugs include opioids, barbiturates, benzodiazepines or amphetamines.
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