WO2007147330A1 - Application des composés de bakuchiol - Google Patents

Application des composés de bakuchiol Download PDF

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Publication number
WO2007147330A1
WO2007147330A1 PCT/CN2007/001840 CN2007001840W WO2007147330A1 WO 2007147330 A1 WO2007147330 A1 WO 2007147330A1 CN 2007001840 W CN2007001840 W CN 2007001840W WO 2007147330 A1 WO2007147330 A1 WO 2007147330A1
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Prior art keywords
disease
psoralen
disorder
phenolic compound
neurological
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PCT/CN2007/001840
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English (en)
Chinese (zh)
Inventor
Lihe Guo
Gang Zhao
Xuesong Wang
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Cell Star Bio-Technologies Co., Limited
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Publication of WO2007147330A1 publication Critical patent/WO2007147330A1/fr

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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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
    • 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
    • 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • 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
    • A61P25/06—Antimigraine agents
    • 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
    • A61P25/08—Antiepileptics; Anticonvulsants
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • 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
    • A61P25/20—Hypnotics; Sedatives
    • 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
    • A61P25/22—Anxiolytics
    • 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
    • A61P25/24—Antidepressants
    • 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
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • 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

Definitions

  • the present invention relates to a novel use of a psoralen phenolic compound, and more particularly to the use of a psoralen phenolic compound in the preparation of a medicament. technical background .
  • Depression is one of the most psychiatric diseases that are depressed, depressed, pessimistic, negative, and can be accompanied by suicidal tendencies. It is the most common mental illness that harms human body and mind health today, and its incidence accounts for 11% of the world population. about. The annual report released by the World Health Organization recently showed: Depression is currently ranked fourth in the world's top ten diseases. The page counts to 2020, 'will be the second largest disease that threatens human health and shortens life expectancy before cancer.
  • Other common psychiatric and neurological diseases include: anxiety disorders, mood disorders, schizophrenia, personality disorders, sychosexual disorders, substance abuse. Drug abuse and dependence, etc. These diseases last from a few weeks to decades, seriously affecting the lives of people in all ages.
  • Dopamine is a major monoamine neurotransmitter in the mammalian brain that controls many functions such as exercise, cognition, emotion, positive reinforcement, feeding, and endocrine regulation. Dopamine plays a key regulatory role in our physical and mental health.
  • the main mechanism of inactivation of dopamine is the reuptake of dopamine by the dopamine transporter (DAT) on the presynaptic membrane.
  • DAT is a 12-transmembrane domain structural protein with sodium ions and chloride ions in the presynaptic membrane, which is the basis for terminating dopamine and maintaining the balance of extracellular dopamine concentration.
  • dopamine transporter the main function of dopamine transporter is to mediate dopamine reuptake, P stripe low synaptic gap dopamine concentration, regulation of dopaminergic signaling in time course and intensity, is the most important factor regulating and maintaining dopamine neurological homeostasis (Giros et al. Nature 1996, 379, 696).
  • Dopamine transporters have been the hallmark of some drugs for the treatment of psychotic neuropathic drugs (methylphenidate, pemoline, bupropion).
  • Norepinephrine is an important monoamine neurotransmitter in the mammalian brain and a physiological hormone. Make As a hormone, it can increase the body's blood pressure rise, vasodilation, and rapid heartbeat under stressful conditions. As a neurotransmitter, norepinephrine mainly regulates activities such as awakening, emotion, and dreams. It is widely present in the post-ganglionic sympathetic and central nervous systems. In neural activity, norepinephrine transporter (NET) can actively release pre-neurocytes into the synaptic cleft, which determines the function of adrenergic neurons, and NET is still a large class of neuropharmaceutical sites. .
  • NET norepinephrine transporter
  • Serotonin is widely distributed in animals and plants. In the human body, the role of serotonin is mainly to transmit neural information. Serotonin can directly affect people's psychological and physiological functions, such as human emotions, sleep, appetite and so on. When the concentration of serotonin is too high, people will be over-excited; if the concentration of serotonin is too low, it will produce a series of mental and psychological morbidities, such as anxiety, panic, tremor paralysis, migraine, phenylketonuria. Symptoms, rheumatoid arthritis, the most important is depression, which causes phobia, obsessive-compulsive disorder and so on.
  • 5-HT is rapidly released from chromaffin cells or serotonergic nerves, but the functioning 5-HT must be transported by a protein called serotonin transporter (SERT).
  • SERT serotonin transporter
  • chromaffin cells or serotonergic neurons the nerve impulse signal is terminated. Therefore, SERT plays an important role in regulating the concentration of 5-HT, thus ensuring normal human function.
  • antidepressant drugs mainly achieve therapeutic purposes by interfering with the activity of the above three neurotransmitters in the brain.
  • clinical antidepressants are mainly second-generation antidepressants (ie, new antidepressants), including selective serotonin (5-HT) reuptake inhibitors (SSRI), and SSRI is fluoxetine.
  • SSRI selective serotonin
  • SSRI SSRI is fluoxetine.
  • Paroxetine Sertraline
  • Sertraline Sertraline
  • Citalopram Fluvoxamine which share a common pharmacological effect: inhibition of 5-HT transporter reuptake of the presynaptic membrane,
  • the 5-HT concentration in the synaptic cleft is antidepressant, but the study found that the existing drugs have no effect on many patients with psychotic diseases.
  • the psoralen phenolic compound is a kind of compound isolated from the traditional Chinese medicine psoralen, which can inhibit the growth of Staphylococcus aureus in vitro, and is mainly used for antibacterial drugs. Since the substance is derived from natural substances, has low toxicity and side effects, and whether it can be used for the treatment of mental diseases and neurological diseases, it will have very important clinical value. Summary of the invention
  • the technical problem to be solved by the present invention is to disclose the application of a psoralen phenolic compound in the preparation of a medicament for treating a mental disease or a neurological disease, to expand the application range of the psoralen phenolic compound, and to satisfy the clinical treatment of mental diseases and The need for neurological diseases.
  • Another technical problem to be solved by the present invention is to disclose a method for treating psychotic diseases and neurological diseases.
  • the structural formula of the psoralen phenolic compound of the present invention is:
  • R 2 , 3 are respectively hydrogen or a halogen group.
  • the acyl group of 8 refers to an acyl group of a branched or branched carboxylic acid having 1 to 8 carbon atoms, such as formyl group, acetyl group, propionyl group, isopropionyl group, butyryl group, tert-butanoyl group, pentyl group Acyl, pivaloyl, hexanoyl, heptanoyl, octanoyl and the like.
  • the above halogen group means a fluorine, chlorine, bromine or iodine atom.
  • a chlorine atom is preferred.
  • the present invention also relates to a pharmaceutically acceptable salt of a bakuchiol phenolic compound, the pharmaceutically acceptable salt comprising a mineral acid salt or an organic acid salt, preferably a hydrochloride salt, a sulfate salt, a nitrate salt, a phosphoric acid salt a salt, an acetate, an oxalate, a succinate, a tartrate, a methanesulfonate, a maleate, an alkali metal or an alkaline earth metal salt;
  • the present invention also relates to the form of an ester, a carbamate or other conventional "prodrug" of a bakuchiol phenolic compound which, when administered in this form, can be converted into an active moiety in vivo;
  • the most preferred salt is selected from the hydrochloride salt of a psoralen phenolic compound or the acetate of a psoralen phenolic compound;
  • a preferred psoralen phenolic compound is 13-hydroxypsoralen (also referred to herein as B310)
  • the above-mentioned 13-hydroxypsoralen derivative is a compound which is further modified and modified by using 13-light-based bakuchiol as a lead compound to obtain a therapeutic effect on psychotic diseases and neurological diseases. .
  • the psychiatric diseases and neurological diseases according to the present invention are anxiety disorders, mood disorders, schizophrenia, personality disorders, psychosexual disorders, Addiction ⁇ Depression Alzheimer's ⁇ 3 ⁇ 4 (Alzheimer's disease) ⁇ Schizophrenia ⁇ Parkinson's disease ⁇ Insomnia (sleeping disorders), drugs Drug abuse and dependence emesis, irritable bowel syndrome menstrual dysphoria syndrome ⁇ Wilson's disease ⁇ chorea (Chorea) , Derayel bating disorders , mania , obsessive-compulsive disorder , ADHD : , bipolar disorder Migraine epilepsy > multiple sclerosis > stroke Obesity narcolepsy or Tourette, s syndrome (Tourette's syndrome), tremor palsy, migraine. Depression is preferred.
  • the psoralen phenolic compound can be prepared by a method disclosed in the literature (Cecilia L et al Phytoc emistry 1996, 42(5): 1299) or a commercially available product;
  • the form of the psoralen phenolic compound in the form of an ester, a carbamate or other conventional "prodrug” can be prepared by the method disclosed in the literature; or a commercially available product such as a product of Sigma;
  • the bakuchiol phenolic compound or its salt, and the psoralen phenolic compound of the present invention are serotonin transporters, dopamine in the form of esters, carbamates or other conventional "prodrugs". Transporter and norepinephrine transporter multiple inhibitors;
  • the psoralen phenolic compound provided by the invention can selectively inhibit dopamine transporter, norepinephrine transporter and serotonin transporter, and restore endogenous monoamine neurotransmitters in the synaptic cleft to a normal range. To achieve Treats the effects of mental and or neurological diseases.
  • the test also proves that the bakuchiol phenolic compound or its salt, and the psoralen phenolic compound of the present invention are less toxic in the form of esters, carbamates or other conventional "prodrugs"; It is superior to existing clinical antidepressants such as bupropion hydrochloride in the treatment of mental and neurological diseases, especially in the treatment of depression.
  • the bakuchiol compound or a salt thereof, and the psoralen compound may be in the form of an ester, a carbamate or other conventional "prodrug" in a pharmaceutically acceptable carrier.
  • the form, applied to the patient in need of treatment, the dosage of the bakuchiol phenolic compound is not particularly limited, and any suitable dose may be used, and the general dose is
  • the carrier refers to a conventional pharmaceutical carrier in the pharmaceutical field, such as a diluent, an excipient such as water, a filler such as starch, sucrose, etc., a binder, such as a cellulose derivative gelatin, polyvinylpyrrolidone, etc. , lubricants, such as talcum powder.
  • a conventional pharmaceutical carrier in the pharmaceutical field such as a diluent, an excipient such as water, a filler such as starch, sucrose, etc., a binder, such as a cellulose derivative gelatin, polyvinylpyrrolidone, etc. , lubricants, such as talcum powder.
  • the bakuchiol phenolic compound of the present invention or a salt thereof, and the bakuchiol phenolic compound may be orally administered in the form of an ester, a carbamate or other conventional "prodrug" to the above carrier.
  • the form of snorting, intravenous or subcutaneous injection is applied to a patient in need of such treatment.
  • the psoralen phenolic compound of the present invention or a salt thereof, and various preparations of the psoralen phenolic compound in the form of an ester, a carbamate or other conventional "prodrug" may be used in the pharmaceutical field.
  • Methods of Preparation Examples of specific pharmaceutically acceptable carriers and excipients that can be used in formulating the oral dosage forms of the present invention are described in U.S. Patent No. 3,903,297, issued toS.
  • the bakuchiol phenolic compound or a salt thereof, and the psoralen compound have a weight content of 0.1 to 99.9% in the form of an ester, a carbamate or other conventional "prodrug", preferably The content is 0.5 to 90%.
  • the invention also includes a method of treating a psychiatric disorder and a neurological disorder.
  • the method comprises: administering to a subject in need of treatment an effective amount of a composition of a bakuchiol phenolic compound or a salt thereof.
  • the psoralen phenolic compound is 13-hydroxypsoralen or a derivative thereof.
  • composition of the bakuchiol phenolic compound or a salt thereof of the present invention can also be used in combination with other drugs for treating mental diseases and neurological diseases, depending on various needs.
  • the psoralen phenolic compound provided by the present invention proves that the compound selectively inhibits the dopamine transporter, the norepinephrine transporter and the serotonin transporter by in vitro experiments and in vivo experiments in animals, and Y -
  • the effects of aminobutyric acid transporter and L-glutamate transporter have no effect, and the compounds are not toxic to cells; at the same dose, the anti-depressant effect of bakuchiol is significantly better than the current clinical antidepressant.
  • Bupropion hydrochloride Therefore, this kind of compound will provide new drug choices for clinical treatment of mental diseases and neurological diseases, and has a good market prospect.
  • Figure 1 13 - Inhibition of the uptake activity of dopamine transporter by light-based bakuchiol (B310).
  • Figure 6 Toxicity of 13-hydroxypsoralen (B310) to CHO cells.
  • Example 1 Establishment of an in vitro screening model.
  • the present invention relates to experimental methods of conventional molecular biology, which are widely known in the art and are
  • the 5-HTT, NET, DAT, and GAT-1 full-length coding sequences of the rat were cloned into the pCDNA3 vector (invitrogen, USA) and transfected into Chinese hamsters by electroporation.
  • Ovarian cell (CHO) cells were cultured 48 hours later in 1640 medium containing G418. After 10 days, all the control cells died, and the experimental group formed many cell clones. After picking up the clone for one week, the cells were covered with the bottom of the well, and the medium was aspirated, and digested with trypsin.
  • the cells in each well are inoculated into the corresponding wells of two 96-well plates. After the cells have filled the bottom of the well, one of the plates is used for isotope flow measurement. The corresponding one of the plates is transported in a highly active well. Cell step by step Expanded culture, each stage is tested for isotope flow rate, and the cell line with higher transport activity is selected. Finally, the cell clones with the highest transport activity (named S6, NET, D8, GAT-1 cells) are selected to preserve the expression. CHO cell line of four neurotransmitters of serotonin, norepinephrine, dopamine, and gamma-aminobutyric acid.
  • S6, NET, D8, and GAT-1 cells were cultured in a 48-well plate (Costar) to plate (about 60,000 cells per well). The culture solution was discarded, washed once with PBS, and the PBS solution was aspirated, 90 ul of HBS (10 mM Hepes, 100 mM NaCl, pH 8.0) was added to each well, and incubated at 25 ° C for 10 minutes, and 10 ul of HBS reaction solution was added to each well.
  • the experimental group and the positive control drug were added with 80 ul of HBS, lOul of different concentrations of 13-hydroxy bakuchiol (B310) and the positive control drug, benzophenone (BPR), and 10 ul of 3 H-labeled substrate (S6 using 3 H-5).
  • the effect on glutamate transporter uptake activity was determined by using COS-7 cells as a screening model.
  • 3 H-Glutamic Acid and 3 H-Asparate Acid were used to replace the isotopes in the above reactions.
  • ImM Glutamic Acid and AsparateAcid were used as negative controls. change.
  • 13-hydroxypsoralen (B310) also showed strong inhibitory activity against dopamine transporter (DAT) at a concentration of 0.1 ⁇ -10 ⁇ M. It can inhibit 21.9% at O.luM concentration, 62.5% at 1 ⁇ M, and 88.7.% at 10uM.
  • DAT dopamine transporter
  • the inhibitory effect of B3i D8 cell dopamine uptake activity was comparable to that of the positive control drug bupropion (BPR), 0.05, and 7 concentrations were taken at a concentration range of 0.1 ⁇ ⁇ -10 ⁇ ⁇ .
  • the IC50 of B310 on dopamine uptake activity was calculated to be 8.3341 ⁇ 4.5702 ⁇ by semi-logarithmic curve correlation analysis.
  • B310 has a significant inhibitory effect on the uptake activity of norepinephrine transporter at ⁇ . ⁇ ⁇ ⁇ -10 ⁇ ⁇ ( ⁇ 0.05) ⁇ 0.1% at 0.1 ⁇ ⁇ , ⁇ ⁇ ⁇ concentration The inhibition was 56.1%, and 89.1% was inhibited at a concentration of 10 ⁇ M. At ⁇ ⁇ ⁇ concentration, the inhibitory effect of B310X inch NET cell uptake was comparable to the positive control drug bupropion (BPR). iPXH is shown in Figure 2.
  • 13-hydroxypsoralen (B310) has inhibitory activity against dopamine transporter, norepinephrine transporter and serotonin transporter, and the inhibitory effect on the uptake activity of serotonin transporter is strong.
  • the positive control drug bupropion (BPR) had no effect on the ⁇ -aminobutyric acid transporter and glutamate transporter activity. Therefore, 13-light-based bakuchiol (B310) is selective for the inhibition of monoamine neurotransmitter transporters.
  • CHO cells were cultured in 1640 medium (containing 10% calf serum), and after being filled with culture dishes, trypsinized and digested 10 kinds of cells in 48-well cell plates, and continued to culture until the number of cells reached about 10 5 , respectively.
  • the control group was added with ⁇ control solution (HBS containing 1% DMS0), and the different doses of the drug were added with different concentrations of 13-hydroxypsoralen, so that the final concentrations were lmm, 0.1 mM and 0.01, respectively. mM.
  • the culture was continued for 24 hours, and MTT was added at the 20th hour to give a final concentration of 0.5 mg/ml.
  • the culture was aspirated, 100% DMSO was added, and incubation was carried out for 10 minutes at 37 °C. Transfer to a 96-well plate and measure the OD value of each well with a microplate reader at a wavelength of 570 nm.
  • Example 5 Effect of 13-hydroxypsoralen on behavioral despair model animals 21 male Balb/c mice, weighing 20 to 24 g, were purchased from the Experimental Animal Center of Shanghai Institute of Biological Sciences. Free to drink and drink for a week. The mice were randomly divided into three groups: control group, 7 saline containing 10% DMSO, and intraperitoneal injection with the treatment group; 7 positive control group, bupropion hydrochloride (physiology dissolved in 10% DMSO) 10 mg/kg body weight in saline, intraperitoneal injection; 7 in the treatment group, 13-hydroxypsoralen (dissolved in 10% DMSO in normal saline) 10 mg/kg body weight, intraperitoneal injection.
  • control group 7 saline containing 10% DMSO, and intraperitoneal injection with the treatment group
  • 7 positive control group bupropion hydrochloride (physiology dissolved in 10% DMSO) 10 mg/kg body weight in saline, intraperitoneal injection
  • 7 in the treatment group 13-hydroxypsoralen
  • mice After the animals or the control solution were treated for half an hour, the mice were fixed with a tape at the upper end of the cross-bar of the open container, and the head was drooped. The two recorders simultaneously each animal for 6 minutes. No time (desperate time). Struggling and desperate judgment methods: Struggling to show the body of the limbs constantly moving, desperation mainly shows that the animal does not move, the two forelimbs are contracted, and occasionally the hind limbs have slight activity. The average recorded data of the two recorders was used as the immobility time of each animal (Editor Zhang Juntian. Modern Pharmaceutical Research Methods, Beijing Medical University and Peking Union Medical University, 1998, first edition).
  • 5000 mg of l3-light-based bakuchiol was dissolved in 100 mg of water to prepare an aqueous solution, which was dissolved by heating.
  • the mixture is evenly mixed, and the injection solution which is dispensed into a concentration of 10 mg / 2 ml / is filled in a vial and sealed to be sterilized.

Abstract

L'invention concerne l'application des composés de bakuchiol à la préparation d'un médicament pour traiter la psychopathie ou la neuropathie. Les composés de bakuchiol peuvent inhiber de façon sélective l'activité de la protéine de transport de la dopamine, la protéine de transport de la norépinéphrine et la protéine de transport de 5-HT, tout en n'ayant aucune influence sur l'activité de la protéine de transport de la Ϝ-propalanine et de l'acide L-glutamique et en ne présentant pas de cytotoxicité.
PCT/CN2007/001840 2006-06-13 2007-06-11 Application des composés de bakuchiol WO2007147330A1 (fr)

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CN2006100276430A CN101088498B (zh) 2006-06-13 2006-06-13 补骨脂酚类化合物的应用
CN200610027643.0 2006-06-13

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CN103316126A (zh) * 2013-05-23 2013-09-25 太仓市胜舟生物技术有限公司 一种治疗精神***症的中药
CN103263513A (zh) * 2013-05-23 2013-08-28 太仓市胜舟生物技术有限公司 一种中药在制备偏执型精神病药物中的应用

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