CN113842388A - Application of huperzine A in treating chronic ischemic cerebrovascular disease - Google Patents

Application of huperzine A in treating chronic ischemic cerebrovascular disease Download PDF

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CN113842388A
CN113842388A CN202010601914.9A CN202010601914A CN113842388A CN 113842388 A CN113842388 A CN 113842388A CN 202010601914 A CN202010601914 A CN 202010601914A CN 113842388 A CN113842388 A CN 113842388A
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dementia
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vascular dementia
huperzine
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Shanghai Tin Tsz Bio Valley Biological Engineering Co ltd
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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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4748—Quinolines; Isoquinolines forming part of bridged ring systems
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

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Abstract

The invention provides an application of huperzine A in treating chronic ischemic cerebrovascular diseases. Experiments prove that the huperzine A can safely and effectively treat chronic ischemic cerebrovascular diseases.

Description

Application of huperzine A in treating chronic ischemic cerebrovascular disease
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to application of huperzine A in treating chronic ischemic cerebrovascular diseases, in particular to vascular dementia.
Background
Chronic ischemic cerebrovascular diseases are common diseases which harm human health, patients can suffer from diffuse lacunar choking and encephalatrophy caused by long-term cerebral ischemia, and then a series of symptoms such as dizziness, memory decline, reaction retardation, cognitive and motor dysfunction and the like appear, and the chronic ischemic cerebrovascular diseases increasingly cause people's attention. Chronic ischemic cerebrovascular disease can lead to vascular cognitive impairment. Vascular Cognitive Impairment (VCI) is a syndrome characterized by cerebrovascular damage with or without significant clinical stroke symptoms accompanied by cognitive impairment affecting at least one cognitive region. Vascular cognitive disorders (VCI) include non-dementia vascular cognitive disorders, mild dementia vascular cognitive disorders, vascular dementia (VaD), with vascular dementia (VaD) being the most severe vascular cognitive disorder.
The nerve dysfunction of movement, sensation, cognition and the like of the chronic ischemic cerebrovascular disease seriously affects the life quality of patients, and has huge medical and social burden, so an effective treatment method is still lacked.
Therefore, there is a need in the art to provide safe and effective drugs for treating chronic ischemic cerebrovascular diseases.
Disclosure of Invention
The invention aims to provide the application of huperzine A in treating chronic ischemic cerebrovascular diseases, and the huperzine A can safely and effectively treat the chronic ischemic cerebrovascular diseases.
In a first aspect of the present invention, there is provided a use of huperzine a or a pharmaceutically acceptable salt thereof for preparing a pharmaceutical composition or preparation for preventing and/or treating chronic ischemic cerebrovascular diseases.
In another preferred embodiment, the chronic ischemic cerebrovascular disease comprises vascular cognitive disorders.
In another preferred embodiment, the vascular cognitive disorder (VCI) is selected from the group consisting of: non-dementia vascular cognitive disorder, mild dementia vascular cognitive disorder, vascular dementia (VaD), or a combination thereof, preferably vascular dementia (VaD).
In another preferred example, the vascular dementia is vascular dementia caused by chronic ischemic cerebrovascular disease.
In another preferred example, the vascular dementia is vascular dementia caused by ischemia and hypoxic hypoperfusion, subcortical white matter lesions, hemorrhagic lesions, and/or inflammatory cerebrovascular lesions.
In another preferred example, the vascular dementia is vascular dementia in patients with cerebral lacunar infarction, subcortical arterial infarction, basal ganglia hemorrhage and/or apical lobe infarction.
In another preferred embodiment, the vascular dementia is mild dementia (MMSE score of 18-24) or moderate dementia (MMSE score of 12-17).
In another preferred embodiment, the pharmaceutical composition or formulation further comprises a pharmaceutically acceptable carrier.
In another preferred embodiment, the pharmaceutical composition or formulation is in a dosage form selected from the group consisting of: liquid formulations (e.g., solutions, emulsions, suspensions), solid formulations (e.g., lyophilized formulations).
In another preferred embodiment, the dosage form of the pharmaceutical composition is selected from the group consisting of: injection (such as injection or powder injection), and oral preparation (such as capsule, tablet, pill, powder, granule, syrup, oral liquid or tincture), preferably, the dosage form is oral preparation.
In a second aspect of the present invention, there is provided a method for the treatment and prevention and/or treatment of chronic ischemic cerebrovascular disease, comprising the step of administering a therapeutically effective amount of huperzine a or a pharmaceutically acceptable salt thereof to a subject in need thereof.
In another preferred embodiment, the subject is a mammal, preferably a human, rat, mouse, dog or cat.
It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be reiterated herein, but to the extent of space.
Detailed Description
The inventor provides the application of huperzine A in treating chronic ischemic cerebrovascular diseases through extensive and intensive research and extensive screening and testing. Experiments of the invention prove that the huperzine A can obviously improve the cognitive function of a patient with vascular dementia, reduce the dementia degree and improve the life self-care ability of the patient, and the cerebral lesion of the patient taking the huperzine A is obviously improved, which indicates that the huperzine A can be used as a medicine for treating chronic ischemic cerebrovascular diseases, in particular vascular dementia. The present invention has been completed based on this finding.
Term(s) for
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
As used herein, the term "about" when used in reference to a specifically recited value means that the value may vary by no more than 1% from the recited value. For example, as used herein, the expression "about 100" includes 99 and 101 and all values in between (e.g., 99.1, 99.2, 99.3, 99.4, etc.).
As used herein, the term "comprising" or "includes" can be open, semi-closed, and closed. In other words, the term also includes "consisting essentially of …," or "consisting of ….
The term "room temperature" as used herein means a temperature of 4-40 ℃, preferably 25 ± 5 ℃.
As used herein, the terms "prevention" or "treatment" include disease-modifying treatment and symptomatic treatment, either of which may be prophylactic (i.e., to prevent, delay or lessen the severity of a symptom prior to the onset of the symptom)) or therapeutic (i.e., to lessen the severity and/or duration of a symptom after the onset of the symptom). "prevention" and "treatment" as used herein include delaying and stopping the progression of the disease, and do not require 100% inhibition, eradication, or reversal. In some embodiments, the reduction, prevention, inhibition, and/or reversal is, e.g., at least about 1%, 10%, at least about 30%, at least about 50%, or at least about 80% as compared to a pharmaceutical composition comprising a compound of formula I in the absence of a compound of formula I of the present invention.
Active ingredient
Huperzine A (formula I, Huperzine-A) or pharmaceutically acceptable salt thereof serving as an active ingredient of the Huperzine A compound;
Figure BDA0002558789970000031
as used herein, "pharmaceutically acceptable salt" refers to a salt formed by a compound of the present invention with an acid or base that is suitable for use as a pharmaceutical. Pharmaceutically acceptable salts include inorganic and organic salts. One preferred class of salts is that formed by reacting a compound of the present invention with an acid. Suitable acids for forming the salts include, but are not limited to: inorganic acids such as hydrochloric acid, hydrobromic acid, hydrofluoric acid, sulfuric acid, nitric acid, phosphoric acid, etc., organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, picric acid, methanesulfonic acid, phenylmethanesulfonic acid, benzenesulfonic acid, etc.; and acidic amino acids such as aspartic acid and glutamic acid. One preferred class of salts is that formed by reacting a compound of the present invention with a base. Suitable bases for salt formation include, but are not limited to: inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate and sodium phosphate, and organic bases such as ammonia, triethylamine, diethylamine and piperazine.
The compounds of the present invention may be amorphous, crystalline or mixtures thereof.
The compounds of the present invention may be stereoisomers thereof.
The compound of formula I of the present invention can be obtained by extraction from plants such as huperzia serrata (tnunb) through alcohol extraction, chromatography, etc., and can be purchased commercially or synthesized by synthesis methods in the prior art using commercially available raw materials. The compounds of the present invention can be extracted or synthesized by one of ordinary skill in the art according to the prior art. The extract or synthesized compound can be further purified by column chromatography, high performance liquid chromatography or crystallization.
They can also be chemically synthesized by methods known in the art.
Pharmaceutical compositions, methods of administration and uses
The active ingredient of the present invention has the effect of preventing and/or treating chronic ischemic cerebrovascular diseases, and thus can be used for preparing pharmaceutical compositions for preventing and/or treating chronic ischemic cerebrovascular diseases.
Preferably, the chronic ischemic cerebrovascular disease is Vascular Cognitive Impairment (VCI).
In another preferred embodiment, the vascular cognitive disorder is selected from the group consisting of: non-dementia vascular cognitive disorder, mild dementia vascular cognitive disorder, vascular dementia (VaD), or a combination thereof, preferably vascular dementia (VaD).
In another preferred example, the vascular dementia is vascular dementia caused by chronic ischemic cerebrovascular disease.
In another preferred example, the vascular dementia is vascular dementia caused by ischemia and hypoxic hypoperfusion, subcortical white matter lesions, hemorrhagic lesions, and/or inflammatory cerebrovascular lesions.
In another preferred example, the vascular dementia is vascular dementia in patients with cerebral lacunar infarction, subcortical arterial infarction, basal ganglia hemorrhage and/or apical lobe infarction.
In another preferred embodiment, the vascular dementia is mild dementia (MMSE score of 18-24) or moderate dementia (MMSE score of 12-17).
The active ingredients of the present invention may be administered alone or in combination with other pharmaceutically acceptable compounds, including (but not limited to): hypotensive agents (e.g., angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers (e.g., valsartan, losartan, alisartan medoxomil, etc.)), hypolipidemic agents (e.g., statins, fibrates, nicotinic acids, cholesterol absorption inhibitors); a medicament for treating senile dementia, such as donepezil hydrochloride, or a combination thereof.
The pharmaceutical composition of the present invention can be used for preventing and/or treating chronic ischemic cerebrovascular diseases.
In another preferred embodiment, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier.
In the pharmaceutical composition of the present invention, the first active ingredient and the second active ingredient may be formulated separately or mixed together to make a formulation.
As used herein, "safe and effective amount" refers to: the amount of the compound is sufficient to significantly improve the condition without causing serious side effects. Typically, the pharmaceutical composition contains 1-2000mg of a compound of the invention per dose, more preferably, 10-500mg of a compound of the invention per dose. Preferably, said "dose" is a capsule or tablet.
"pharmaceutically acceptable carrier" refers to: one or more compatible solid or liquid fillers or gel substances which are suitable for human use and must be of sufficient purity and sufficiently low toxicity. By "compatible" is meant herein that the components of the composition are capable of intermixing with the compound of formula I without significantly diminishing the pharmaceutical efficacy of the compound. Examples of pharmaceutically acceptable carrier moieties are cellulose and derivatives thereofBiological (such as sodium carboxymethylcellulose, sodium ethyl cellulose, cellulose acetate, etc.), gelatin, pulvis Talci, solid lubricant (such as stearic acid, magnesium stearate), calcium sulfate, vegetable oil (such as soybean oil, oleum Sesami, peanut oil, oleum Olivarum, etc.), polyalcohol (such as propylene glycol, glycerol, mannitol, sorbitol, etc.), emulsifier (such as Tween, etc.)
Figure BDA0002558789970000051
) Wetting agents (e.g., sodium lauryl sulfate), coloring agents, flavoring agents, stabilizers, antioxidants, preservatives, pyrogen-free water, and the like.
The mode of administration of the pharmaceutical composition of the present invention is not particularly limited, and representative modes of administration include (but are not limited to): oral, rectal, parenteral (intravenous, intramuscular, or subcutaneous), and topical administration.
Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In these solid dosage forms, the active compound is mixed with at least one conventional inert excipient (or carrier), such as sodium citrate or dicalcium phosphate, or with the following ingredients: (a) fillers or extenders, for example, starch, lactose, sucrose, glucose, mannitol and silicic acid; (b) binders, for example, hydroxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose and acacia; (c) humectants, for example, glycerol; (d) disintegrating agents, for example, agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain complex silicates, and sodium carbonate; (e) slow solvents, such as paraffin; (f) absorption accelerators, e.g., quaternary ammonium compounds; (g) wetting agents, such as cetyl alcohol and glycerol monostearate; (h) adsorbents, for example, kaolin; and (i) lubricants, for example, talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, or mixtures thereof. In capsules, tablets and pills, the dosage forms may also comprise buffering agents.
Solid dosage forms such as tablets, dragees, capsules, pills, and granules can be prepared using coatings and shells such as enteric coatings and other materials well known in the art. They may contain opacifying agents and the release of the active compound or compounds in such compositions may be delayed in release in a certain part of the digestive tract. Examples of embedding components which can be used are polymeric substances and wax-like substances. If desired, the active compound may also be in microencapsulated form with one or more of the above-mentioned excipients.
Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups or tinctures. In addition to the active ingredient, the liquid dosage forms may contain inert diluents commonly employed in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, propylene glycol, 1, 3-butylene glycol, dimethylformamide and oils, especially cottonseed, groundnut, corn germ, olive, castor and sesame oils or mixtures of such materials and the like.
In addition to these inert diluents, the compositions can also contain adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents.
Suspensions, in addition to the active ingredients, may contain suspending agents as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum methoxide and agar, or mixtures of these materials, and the like.
Compositions for parenteral injection may comprise physiologically acceptable sterile aqueous or anhydrous solutions, dispersions, suspensions or emulsions, and sterile powders for reconstitution into sterile injectable solutions or dispersions. Suitable aqueous and nonaqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols and suitable mixtures thereof.
Dosage forms for topical administration of the compounds of the present invention include ointments, powders, patches, sprays, and inhalants. The active ingredient is mixed under sterile conditions with a physiologically acceptable carrier and any preservatives, buffers, or propellants which may be required if necessary.
In the present invention, the general range of therapeutically effective dosages for compounds of formula I will be: about 1 to 2000 mg/day, about 10 to about 1000 mg/day, about 10 to about 500 mg/day, about 10 to about 250 mg/day, or about 10 to 100 mg/day. A therapeutically effective dose will be administered in one or more doses. It will be understood, however, that the specific dose of the active ingredients of the invention for any particular patient will depend upon a variety of factors such as the age, sex, body weight, general health, diet, individual response, time of administration, severity of the condition to be treated, the activity of the particular compound administered, the dosage form, mode of application and concomitant drugs. A therapeutically effective amount for a given situation can be determined using routine experimentation and is within the ability and judgment of the clinician or physician. In any event, the active ingredient will be administered in multiple doses based on the individual condition of the patient and in a manner that allows for the delivery of a therapeutically effective amount.
The main advantages of the invention include:
1. the huperzine A can obviously improve the cognitive function of a patient with vascular dementia, reduce the dementia degree and improve the life self-care ability of the patient, and the cerebral lesion of the patient taking the huperzine A is obviously improved, which indicates that the huperzine A can be used as a medicine for treating chronic ischemic cerebrovascular diseases, in particular to vascular dementia.
2. The huperzine A is a known compound, has definite safety, and can provide a convenient choice for rapidly developing a medicament for treating chronic ischemic cerebrovascular diseases.
The invention is further illustrated with reference to specific embodiments. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Experimental procedures without specific conditions noted in the following examples, generally followed by conventional conditions, such as Sambrook et al, molecular cloning: the conditions described in the Laboratory Manual (New York: Cold Spring Harbor Laboratory Press,1989), or according to the manufacturer's recommendations. Unless otherwise indicated, percentages and parts are by weight.
Example 1
(one) case selection
The following cases were excluded: history of psychiatric disorders; acute phase of cerebral ischemic attack; history of central nervous system infections; patients with nervous system diseases such as multiple sclerosis, myasthenia, demyelinating diseases, etc.; history of neurological tumors; history of brain trauma; sequelae of cerebral hemorrhage or cerebral infarction; patients with epilepsy, renal insufficiency, mechanical intestinal obstruction, angina pectoris; patients with poor cardiac function and chronic heart failure.
The eligible cases were selected as 180 trial cases, with a balance of male and female cases aged 50-75 years.
(II) inclusion criteria
Cerebral ischemia or cerebral infarction can be induced by ischemia and hypoxic hypoperfusion, subcortical white matter lesion, hemorrhagic lesion, inflammatory cerebrovascular lesion and other diseases, thereby causing vascular dementia. Neuroimaging is very helpful for the confirmation of vascular dementia and the identification of specific vascular dementia subtypes, and the two types of subcortical dementia are easy to distinguish whether the white matter disease is the main or lacunar infarction is the main.
In order to meet the requirement of completely meeting the vascular dementia case, the key index is set as the skull MRI or CT to prompt the lacunar infarction; cranial CTA had no significant cerebrovascular stenosis (less than 30%), or occlusion.
The auxiliary index is set as: functional and cognitive dysfunction (decline in memory, orientation, attention, language, visual space, performance, motor control, and behavior) occurs.
(III) methods of treatment
Patients meeting the group entry criteria were divided into three groups, high dose huperzine a tablet group, medium dose huperzine a tablet combination, and placebo group.
Each group of patients was treated with huperzine A drug orally for 3 months.
The patients in the high dose huperzine A tablet group will take 4 oral huperzine A tablets (0.05 mg/tablet) 2 times a day, and the patients in the medium dose huperzine A tablet group will take 3 oral huperzine A tablets +1 blank placebo tablet 2 times a day; the control group took 2 times daily 4 tablets each time of the placebo tablet.
A blank placebo tablet. The character is the same as that of huperzine A tablet.
(IV) safety Observation
Before and after treatment, the subjects were compared with tests such as blood routine, urine routine, liver function, kidney function, and electrocardiogram.
(V) therapeutic criteria and judgment
Collecting venous blood by detection indexes, detecting apolipoprotein E by a method of amplifying gene segments by a PCR technology, and biochemically analyzing plasma homocysteine; the method is characterized in that the acetylcholine enzyme, choline acetyltransferase and butyrylcholine enzyme are detected by collecting venous blood plasma and adopting a liquid chromatography-mass spectrometry (LC-MS) mode.
The cognitive function of the patient is detected by MMSE (simple mental state scale), the dementia degree of the patient is detected by CDR (clinical dementia scale), and the self-care ability of the patient in daily life is detected by ADL (daily life activity ability scale). Before and after administration, the patient was examined every 4 weeks for 1 time while observing changes in vital signs (blood pressure, pulse, body weight and respiration), and examined for blood routine, urine routine, liver function, kidney function, electrocardiogram, chest X-ray film, etc., and adverse reactions during administration were recorded.
The effect is shown: the main symptoms are basically recovered, the mind is clear, the orientation is healthy, the answer to the questions is correct, the response is sensitive, the life is self-care, and the general social activities can be carried out.
The method has the following advantages: the main mental symptoms are relieved or partially disappeared, the life is basically self-care, the answer to questions is basically correct, but the reaction is still slow, and the intelligence and personality are still partially impaired.
And (4) invalidation: no change in the main symptoms, or development of disease conditions, inability to take care of life, inaccurate answer to questions, mental stiffness and fool feeling
The statistical method is characterized in that SPSS 13.0 statistical software is used for statistical processing, all data are tested by t, and P <0.05 is the difference with statistical significance.
(VI) results
TABLE 1 administration of huperzine A
Figure BDA0002558789970000091
TABLE 2 comparison of MMSE, CDR, ADL scores before and after treatment
Figure BDA0002558789970000092
After 12 weeks of treatment, the MMSE score of the treatment group is higher than that of the treatment group before and after the control group (P < 0.05); both the ADL scores of the treatment group and the control group are reduced (P <0.05) compared with the ADL score before treatment, and the ADL score after treatment of the treatment group is reduced more obviously (P <0.01) compared with the ADL score of the control group
Note: p <0.05 compared to pre-treatment; p <0.05 compared to control.
TABLE 3 imaging changes (example%) of brain lesions before and after treatment
Figure BDA0002558789970000093
Figure BDA0002558789970000101
The imaging change of the cerebral lesion parts before and after treatment, the subcortical arterial infarction, the basal ganglia hemorrhage and the apical lobe infarction of the patient after treatment are obviously reduced compared with the positions before treatment, and the difference has statistical significance.
TABLE 4 comparison of clinical efficacy of each group
Figure BDA0002558789970000102
Note: p <0.05 compared to control group
By treating 180 patients with vascular dementia with huperzine A and blank placebo, the pathological changes of subcortical artery infarction, basal ganglia hemorrhage and apical lobe infarction are remarkably improved compared with those before treatment; the MMSE, CDR and ADL scores of the patients after treatment are all obviously better than those before treatment.
In conclusion, the experimental results of the invention prove that the huperzine A can obviously improve the near memory and spatial position dysfunction caused by cerebral ischemia, obviously improve the neuron degeneration caused by cerebral blood hypoperfusion, has obvious treatment effect on the vascular dementia caused by cerebral ischemia, has obvious improvement on the symptoms of patients and exact clinical treatment effect, and thus, the huperzine A medicament can be used for preparing the medicament for preventing and/or treating the cerebral ischemic diseases.
All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.

Claims (10)

1. Use of huperzine a or a pharmaceutically acceptable salt thereof for preparing a pharmaceutical composition or preparation for preventing and/or treating chronic ischemic cerebrovascular diseases.
2. The use of claim 1, wherein said chronic ischemic cerebrovascular disease comprises vascular cognitive impairment.
3. The use according to claim 2, wherein the vascular cognitive disorder (VCI) is selected from the group consisting of: non-dementia vascular cognitive disorder, mild dementia vascular cognitive disorder, vascular dementia (VaD), or a combination thereof, preferably vascular dementia (VaD).
4. The use according to claim 3, wherein the vascular dementia is vascular dementia caused by chronic ischemic cerebrovascular disease.
5. Use according to claim 3, wherein the vascular dementia is vascular dementia caused by ischemia and hypoxic hypoperfusion, subcortical white matter lesions, hemorrhagic lesions and/or inflammatory cerebrovascular lesions.
6. The use according to claim 3, wherein the vascular dementia is vascular dementia in patients with cerebral lacunar infarction, subcortical infarction, basilar hemorrhage and/or apical lobe infarction.
7. The use according to claim 3, wherein the vascular dementia is mild dementia (MMSE score 18-24) or moderate dementia (MMSE score 12-17).
8. The use of claim 1, wherein the pharmaceutical composition or formulation further comprises a pharmaceutically acceptable carrier.
9. The use of claim 1, wherein the pharmaceutical composition or formulation is in a dosage form selected from the group consisting of: liquid formulations (e.g., solutions, emulsions, suspensions), solid formulations (e.g., lyophilized formulations).
10. The use of claim 1, wherein the pharmaceutical composition or formulation is in a dosage form selected from the group consisting of: injection (such as injection or powder injection), and oral preparation (such as capsule, tablet, pill, powder, granule, syrup, oral liquid or tincture), preferably, the dosage form is oral preparation.
CN202010601914.9A 2020-06-28 2020-06-28 Application of huperzine A in treating chronic ischemic cerebrovascular disease Pending CN113842388A (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080090808A1 (en) * 2006-10-17 2008-04-17 Franklin Volvovitz Pharmaceutical compositions and methods for preventing, treating, or reversing neuronal dysfunction
CN102813653A (en) * 2012-08-22 2012-12-12 郭涛 Medicine used for treating cerebral ischemic dementia and preparation method for medicine
CN102872016A (en) * 2012-03-22 2013-01-16 北京阜康仁生物制药科技有限公司 Medicine combination
US20130040982A1 (en) * 2010-04-22 2013-02-14 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Oral sustained release formulation of huperzine a
CN103536698A (en) * 2013-11-04 2014-01-29 华润三九医药股份有限公司 New medicine application of traditional Chinese medicinal composition

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080090808A1 (en) * 2006-10-17 2008-04-17 Franklin Volvovitz Pharmaceutical compositions and methods for preventing, treating, or reversing neuronal dysfunction
US20130040982A1 (en) * 2010-04-22 2013-02-14 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Oral sustained release formulation of huperzine a
CN102872016A (en) * 2012-03-22 2013-01-16 北京阜康仁生物制药科技有限公司 Medicine combination
CN102813653A (en) * 2012-08-22 2012-12-12 郭涛 Medicine used for treating cerebral ischemic dementia and preparation method for medicine
CN103536698A (en) * 2013-11-04 2014-01-29 华润三九医药股份有限公司 New medicine application of traditional Chinese medicinal composition

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
李华丽: "养血清脑颗粒联合石杉碱甲治疗血管性痴呆的效果", 《河南医学研究》, vol. 29, no. 3, 28 January 2020 (2020-01-28), pages 481 - 482 *

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