WO2008031322A1

WO2008031322A1 - Application of acetylcholine esterase inhibitor medication of leonurus extractive as cholinomimetic

Info

Publication number: WO2008031322A1
Application number: PCT/CN2007/002456
Authority: WO
Inventors: Shuping Hao; Hui Hao; Shuyu Xiao
Original assignee: Shuping Hao; Hui Hao; Shuyu Xiao
Priority date: 2006-09-10
Filing date: 2007-08-15
Publication date: 2008-03-20
Also published as: CN1915292A

Abstract

Novel application of acetylcholine esterase inhibitor medication of Leonurus extractive as cholinomimetic. The active ingredients of the present extractive are leonurinine, leonurine, general leonurines, leonurine A, cadabine, or mixtures thereof or mixtures of pharmaceutically acceptable salts thereof or mixtures of both, having inhibitory effects on acetylcholine esterase, useful in treating and preventing diseases such as dementia praesenilis, Alzheimer's disease, Parkinson's disease, hysteria, schizophrenia, rheumatoid arthritis, systematic lupus erythematodes, myasthenia, progressive amyotrophy, lower varicosity, thromboangiitis obliterans, ecthyma, psoriasis, vitiligo, anserine disease, hypertension, coronary heart disease, hyperlipidemia, cardio- and cerebro-vascular diseases, aplastic anemia, purpura, intravascular agglutination disseminata, menoxenia and the like.

Description

Description Use of Motherwort Extract as a acetylcholinesterase inhibitor drug for cholinergic compounds

The present invention relates to the use of motherwort extract, in particular to the use of motherwort extract as a acetylcholinesterase inhibitor of a cholinergic agent in the pharmaceutical field.

Background technique:

Lemium (Leomirus) is a Labiatae plant, formerly known as Yu Wei, traditional understanding and indications: irregular menstruation, dysmenorrhea, amenorrhea, postpartum blood stasis, water, blood in the urine, red eyes and swelling, dizziness and pain. Yuweizi is the mature fruit of Motherwort. It has a sweet taste, sweetness, slight cold, and enters the liver. Its function of promoting blood circulation and regulating menstruation is the same as that of motherwort. It has the functions of clearing the liver and improving eyesight, promoting blood circulation and qi, and is used for clinical use in redness, swelling or pain. Eye disease. Motherwort extract includes the existing on the market: Motherwort granules, motherwort cream, motherwort syrup, motherwort oral liquid, motherwort capsule, 茺蔚丸, motherwort injection, people's understanding of the above-mentioned motherwort extract is mainly limited to the traditional treatment of motherwort range. Modern medical research: The main active ingredients of Motherwort are alkaloids, such as: motherwort base, motherwort, motherwort total base, motherwort A and stachydrine. Among them, motherwort (C ₁₃ H ₂₁ 0 ₅ N ₃ ), motherwort total base, and stachydrine have been reported in the existing literature to have direct excitatory effects on various animals in the uterus, which can cause uterine contraction frequency, amplitude, and Increased tension, and the effect of promoting blood circulation, stopping bleeding. The main ingredient of 茺蔚子, 母母草子 is motherwort Ning (Le ₀ mirinine, C ₁₍₎ H ₁₄ 0 ₃ N ₂ ), stachysine and oleic acid. The main components of oleic acid are: linoleic acid (42.62 % ), linolenic acid (29.93%), oleic acid (20.23%), palmitic acid (5.40%), stearic acid (1.57%), etc., in addition to 17 amino acids and 24 mineral elements, and vitamins

Confirmation A-like substance, 茺蔚油 is an extract of 茺蔚子, which contains motherwort, stachydrine and oleic acid. The therapeutic effect of guanwei oil as a drug has not been reported.

Summary of the invention:

The object of the present invention is to provide a new use of motherwort extract, specifically related to motherwort extract, motherwort granules, motherwort cream, motherwort syrup, motherwort oral liquid, motherwort capsule, 茺蔚丸, 茺蔚油, 茺蔚散, 茺蔚 granules , 茺膏、, 茺糖 syrup, 茺口服 oral liquid, 茺胶囊 capsule, motherwort injection as a choline acetylcholine esterase inhibitor in the pharmaceutical field.

In fact, the present invention relates to motherwort extract: motherwort cream, motherwort syrup, motherwort granules, motherwort oral solution, motherwort capsule, 茺蔚丸, 茺蔚油, 茺蔚散, 茺冲冲、, 茺膏、, 茺糖 syrup Agent, Qiwei oral liquid, Qiwei capsule, and motherwort injection as acetylcholinesterase inhibitors of cholinergic drugs.

The present invention relates to the main active ingredients in the extract of Motherwort: motherwort base, motherwort, motherwort total base, motherwort A, stachydrine or a pharmaceutically acceptable salt thereof as an acetylcholinesterase inhibitor of the cholinergic agent.

Involving the main active ingredients in the extract of Motherwort: a mixture of motherwort base, motherwort, motherwort total base, motherwort A, stachyphylline or a pharmaceutically acceptable salt thereof or a mixture of the two as the choline acetylcholine Esterase inhibitor.

It is related to the main active ingredient of motherwort extract, estramustine, stachysine, or pharmaceutically acceptable salt thereof, as an acetylcholinesterase inhibitor of cholinergic drugs.

The motherwort extract is used as a cholestyramine inhibitor of acetylcholine in the preparation and treatment of Alzheimer's disease, Alzheimer's disease, Parkinson's disease, rickets, schizophrenia, and Rheumatoid arthritis, systemic lupus erythematosus, myasthenia gravis, progressive muscular atrophy, varicose veins of the lower extremities, thromboangiitis obliterans, acne, psoriasis, vitiligo, goose wind, hypertension, coronary heart disease, hyperlipidemia , cardiovascular and cerebrovascular disease, aplastic anemia, purpura, disseminated intravascular coagulation, irregular menstruation, cancer, leukemia, hepatitis B, jaundice hepatitis, cirrhosis, glaucoma, cataract, tinnitus, deafness, hair loss, The application of drugs for nephritis, uremia, prostatitis, benign prostatic hyperplasia, prostatic hypertrophy, diabetes insipidus, diabetes, gastroptosis, uterine prolapse, drooping eyelids, hyperthyroidism, and spleen disease.

The method for treating and preventing a disease, comprising administering to a patient a therapeutically effective amount of an active ingredient selected from the group consisting of motherwort, motherwort, motherwort total base, motherwort A, and water stasis. a mixture of a base or a mixture thereof or a pharmaceutically acceptable salt thereof or a mixture of the two.

An extract active ingredient of the use of the active ingredient, motherwort base, motherwort, motherwort total base, motherwort alpha, stachydrine or a mixture thereof or a pharmaceutically acceptable salt thereof, or a mixture of the two together with an adjuvant to form a tablet , capsules, injections, oral liquids, syrups, powders, ointments, oils, pills, granules.

The motherwort extract is used as a acetylcholinesterase inhibitor drug for a cholinergic agent, and a therapeutically effective dose of the active ingredient is administered at a dose of 0.005 to 0.4 g/kg per day per day.

The active ingredient of the motherwort extract 茺蔚油 or motherwort extract is added as an additive to an edible oil or a rubbing cosmetic or a washing daily necessities or an oral care daily necessities.

The ratio of the additive to the additive is 1/5000 to 1/10. In order to better understand the essence of the present invention, the following will separately use the motherwort granules, motherwort cream, motherwort sugar granules, motherwort oral liquid, motherwort capsules, 茺丸丸, 茺油 oil, 茺散、, 茺冲冲、, 茺Pharmacological tests and results of Weiwei, Yuwei syrup, Qiwei oral liquid, Qiwei capsule and motherwort injection to illustrate its new use in the pharmaceutical field. The above five substances have the same pharmacological effects, and the difference is only in the amount used and the time of marked effect.

1. Acute toxicity test of mice

Oral administration: 10 healthy male mice, weighing 17~24 _g , administered by oral administration of motherwort extract of motherwort, motherwort cream, motherwort syrup, motherwort oral solution, motherwort capsule, 茺蔚丸, 茺蔚油, 茺散、, 茺冲冲、, 茺膏、, 茺糖 syrup, 茺口服 oral liquid, 茺胶囊 capsule, motherwort injection LD50 (ip) = 2452.8 ± 5.42mg / kg (calculated according to motherwort). Injection administration: 10 male mice, weighing 17~24 _g , calculated according to the simplified probability unit method of the motherwort, the LD50(iv)=601.2±45.1mg/kg, and the sudden weakness of the body after 4 to 6 hours of observation. The lower limbs are inactive or paralyzed, but they are conscious and have no effect on body temperature, breathing, and heart rate. The symptoms can return to normal after about four hours, and no death is observed for three days.

2. Biological activity experiment

Ellman analysis

Suitable acetylcholinesterase inhibitors were screened by Ellman analysis. Add human acetylcholinesterase (hAchE) in the buffer to the test chemical / TCM extract, then add Acetylthiocholine (ATCI) substrate and Ellman's reagent (5 ' 5 - disulfide - double - (2-nitrate) Benzoate), DTNB :). By releasing the thiocholine pair AchE inhibitory activity was monitored and the thiocholine was subsequently reacted with DTNB to form a bright yellow product. The optical density of the resulting color developing product was measured using a spectrophotometer.

Motherwort from the aqueous extract was dissolved in 20m _g I ml 50% DMSO, then diluted to become 10, 20, 50, 80, 1 00 Mg / ml for Ellman analysis.

Ellman analysis was performed on 96-well plates as follows: Pre-quantified DOF aqueous extracts in assay buffer (100 mM sodium phosphate buffer, pH 7.4) were mixed with 0.1 unit hAChE (purchased in Sigma). After a brief pre-incubation (ie 10 minutes), the same amount of 12.5 mM Acetylthiocholine (ATC1) was mixed with 10 mM (5'5-dithio-bis-(2-nitrobenzoate), DTNB) Then add the mixture to the well. After 10 minutes, the optical density was measured on a 96-well plate at 415iim. The optical density is inversely proportional to the inhibitory activity.

The test results are shown in Figure 1. The 50Mg I ml of motherwort water extract inhibited MChE activity by more than 80%.

Also selected for the motherwort extract of motherwort extract, motherwort cream, motherwort syrup, motherwort oral liquid, motherwort capsule, 茺蔚丸, 茺蔚油, 茺蔚散, 茺冲冲、, 茺膏、, 茺糖 syrup The anti-acetylcholinesterase activities of the active ingredients of Qiwei Oral Liquid, Qiwei Capsule and Yimucao Injection were tested. They were motherwort (C10H14O3N2), motherwort (C13H2105N3, molecular weight 311.33), motherwort total alkali, Motherwort A, stachydrine (C7H13N02, molecular weight 143.0). All of these are from the China National Institute for the Control of Pharmaceutical and Biological Products of the China Food and Drug Administration.

The selected active ingredient is dissolved in 50% DMS0 below, and 100% DMS0 is not recommended in this assay because it reduces enzyme activity. Ellman analysis was performed on the selected active ingredients, motherwort base, motherwort, motherwort total base, motherwort A, and stachydrine, and the 10-fold dilution was performed at a maximum concentration of 40 M (Fig. 2).

Among all the tested chemicals, motherwort base, motherwort, motherwort total base, motherwort A, and stachydrine showed strong AChE inhibition, and their IC50 were about 5-8 mm (Fig. 2).

To determine the specificity of the motherwort, the motherwort, the motherwort total base, the motherwort A, and the stachydrine for AChE, butyl Acetylcholinesterase (hBchE) was used in the Ellman analysis to replace AchE. hBchE is enriched in red blood cells and is named pseudoesterase, which has a very high homology with AChE. Non-specific binding to hBchE gives severe cholinergic side effects.

Ellman analysis was performed as described above except that hBchE (purchased from sigma) was used. AChE was also used in parallel for Ellman analysis for comparison. Compared with BchE, it showed that motherwort, motherwort, motherwort total base, motherwort A, and stachydrine had higher selectivity for AchE (Figs. 3, 4, 5, 6, and 7).

MTT analysis

The toxicity of selected major MchE inhibitors was tested by MTT assay. Considering that only metabolically active cells can remove the tetrazolium salt MTT to form the formazen dye, the 0D detection at 540 nm is directly proportional to the number of viable cells.

In the neuronal cell line SHSYSY and the mouse neuronal cell line NIE-511, no significant cytotoxicity was detected in 1-50 M of motherwort base, motherwort, motherwort total base, motherwort A, and stachydrine. 8, Figure 9). In the present invention, the term "pharmaceutically acceptable salt" is defined as a soluble salt of an inorganic or organic acid such as motherwort sulfate, motherwort acetate, stachysine hydrochloride or the like. The term "active ingredient" as used in the present invention is defined as the motherwort extract of the motherwort extract, motherwort cream, motherwort syrup, motherwort oral solution, motherwort capsule, 茺蔚丸, 茺蔚油, 茺蔚散, 茺Wei Chong, Qi Wei Ointment, Yu Wei Syrup, Qiwei Oral Liquid, Qiwei Capsule, Motherwort Injection or Motherwort Alkaloids: Motherwort Ning, Motherwort, Motherwort Total Alkaloids, Motherwort A, Stachyphylline or its Drugs An acceptable salt or a mixture of the two. The motherwort granules, motherwort cream, motherwort syrup, motherwort oral liquid, motherwort capsule, and glutinous rice granules of the present invention are all available products, and those skilled in the art can obtain them through existing production processes. The dosage forms of the following motherwort extracts are 茺油、, 茺散、, 茺冲冲、, 茺膏、, 茺糖 syrup, 茺口服 oral liquid, 茺胶囊 capsule, and motherwort injection, which are the same as the existing corresponding dosage forms. The active ingredient alkaloids therein and their extraction in pharmaceutically acceptable salts are known in the art, and the stachysine may also be derived from stachys.

The plant of the present invention is preferably selected from the group consisting of motherwort whole grass, and the motherwort extract used in the present invention is selected from the group consisting of 茺蔚子(益母草子).

The extract of Motherwort includes an extract of water extract, ethanol extract, pressed extract, or other existing methods.

The extract of Motherwort or the alkaloid, alkali salt or a mixture thereof of the above motherwort is made into a pharmaceutically acceptable carrier, and the "pharmaceutically acceptable carrier" refers to an excipient or adjuvant used in the pharmaceutical to promote the processing of the active ingredient into a preparation. . The preparation can be administered orally, intramuscularly, intraperitoneally, subcutaneously or intravenously. Preferred are the preparations, especially those such as tablets, ointments, granules, syrups, capsules, pills, granules and injections, and suitable solutions. Suitable excipients for use in the present invention include fillers such as polysaccharides such as lactose or sucrose, mannitol or sorbitol, cellulose derivatives, magnesium sulfate, calcium phosphate such as tricalcium phosphate or calcium hydrogen phosphate, and such as corn starch , a binder of starch paste such as wheat starch. Suitable adjuvants for use include fluid conditioning agents and lubricants such as talc, silica, stearic acid. The extract of the present invention can be formulated into an injection method such as intravenous, subcutaneous and intramuscular injection, an oral preparation, a suppository or a sublingual tablet. It is prepared by methods generally accepted in the art. Pharmaceutical preparations such as injections, sublingual tablets, tablets, syrups and capsules. Stabilizers and preservatives may be added as needed in the preparation. In the present invention, when the active ingredient or composition is administered orally, it may be in the form of a tablet or a capsule, or an aqueous solution or suspension. When a tablet is used, carriers which are usually used include lactose, mannitol and corn starch, and a lubricant such as magnesium stearate is usually added. If in the form of a capsule, the active compound is administered in a dry gelatin capsule in a dry form, or in a suitable gel or liquid carrier, such as liquid polyethylene glycol or cross-gel, in a soft gelatin capsule. .

The motherwort alkaloids motherwort base, motherwort, motherwort total base, motherwort A, stachydrine, and sputum oil are used as acetylcholinesterase inhibitor drugs for cholinergic drugs for health purposes, The ratio of the above alkaloid or the eucalyptus oil is added to the edible oil, and the addition ratio of the additive and the edible oil is 1/5000 to 1/10, and the preferred addition ratio is 1/500 to 1/50.茺油 oil contains alkaloids motherwort, stachydrine and vitamin A-like substances, 24 mineral elements and a variety of amino acids, which are added to edible oil for long-term consumption. It has the function of positively regulating the human body, improving immunity, supplementing nutrients and trace elements, and achieving health care effects. Or add a certain proportion of the above alkaloids or oyster sauce to various products such as shampoo, moisturizing cosmetics, oral care products, etc., in order to achieve the health care effect of the medicine. 005-0. 4 mg/kg·day The effective dosage of the active ingredient is about 005-0. 4 mg/kg·day. The dosage of the active ingredient is about 005-0. 4 mg/kg·day. Dosing is preferably administered at a dose of 0.01 mg to 1.0 mg per day per day. It is taken every morning and evening, and after taking it for three days, it is taken in half, and seven days is a course of treatment. Take a slight excess, generally do not need drug treatment, adverse reactions can disappear after three to four hours, severe cases: M-like reaction is severely rescued with atropine; N-like reaction can be countered with a small amount of myostatin; Shock: Available Norepinephrine is rescued. After oral administration, it can be digested and absorbed in the small intestine. It can easily penetrate into the cell membrane and easily pass through the blood-brain barrier. Therefore, the central role is strong. In the process of diarrhea, it can be reabsorbed in the kidney, and the post-release effect of synaptic transmission leads to drug efficacy. Long-lasting formation; injection and administration can make the drug rapid and effective, and the transdermal absorption of the drug is good.

The term "effective therapeutic dose" or "effective dose" as used herein means an effective dose of the active ingredient to achieve its intended purpose. The dosage should be varied depending on the condition, sex, age and weight of the patient, the method of administration, the time and interval of administration, and the characteristics, modulation, type, specific effective component, and the like of the pharmaceutical preparation.

Clinical treatment and analysis:

Pharmacology: From the above, we can know that motherwort extract, motherwort granules, motherwort cream, motherwort syrup, motherwort oral liquid, motherwort capsule, 茺蔚丸, 茺蔚油, 茺蔚散, 茺冲冲、, 茺膏、, 茺糖 syrup, Qiwei Oral Liquid, Qiwei Capsule and Motherwort Injection are all acetylcholinesterase inhibitors of cholinergic drugs. Specifically, the motherwort base, the motherwort, the motherwort total base, the motherwort A, and the stachydrine are all acetylcholinesterase inhibitors of the cholinergic agent, namely the acetylcholinesterase inhibitor (AchEI). It can inhibit the activity of acetylcholinesterase for a long time, It can reduce the degradation of the neurotransmitter acetylcholine; acetylcholinesterase inhibitor can inhibit the degradation of acetylcholine in the synaptic cleft space, and can enter the cell, and can excite the cholinergic nerve endings, release Ach, and form the concentration of acetylcholine. High, showing long-lasting M-like and N-like effects, plays a role in the functional activities of the human body: neuromodulation and humoral regulation based on normal, healthy and upward physiological effects, this regulation is positive regulation, and the mode of action is dual The sorghum can be reduced to normal, and the low can rise to normal, which can promote the restoration of the relative stable balance of various physical and chemical factors in the human body. In addition, acetylcholine has neuroprotective effects on muscarinic receptor and nicotinic receptor agonism.

Motherwort granules, motherwort cream, motherwort syrup, motherwort oral solution, motherwort capsule, 茺蔚丸, 茺蔚油, 茺蔚散, 茺蔚冲, 茺蔚膏, 茺蔚 syrup, 茺蔚 oral solution, 茺蔚胶囊M-like effects of the active ingredients of Motherwort Injection, Motherwort, Motherwort, Motherwort, Motherwort A and Stachyphylline: (1) Increased glandular secretion: enhanced fluid regulation, hormones and nerves in the body The secretion of the normal mass ratio increases or decreases, thereby forming a unified equilibrium mechanism between the two, and the function of the neuromodulation is strengthened by the regulation of body fluids, thereby forming a benign cycle of humoral regulation and neuromodulation. Relative enhancement and inhibition of hormones and neurotransmitters, increased or decreased fluid between organ tissues (such as decreased muscle moisture in the legs, increased water in the blood vessels), promotes metabolism, enhances human growth, development and reproductive function. Immune Function. The medicine of the invention can enhance the purifying function of blood, establish a long-term blood improvement mechanism, and the main leading role is: the liver is the largest gland of the human body, its secretion is strengthened, and the function of promoting liver biotransformation is strengthened. Reducing the toxins in the blood, combined with the M-like action of the drug, causes the blood vessels of the body to dilate and relax, resulting in an increase in the volume of the blood vessels, and the volume of the blood vessels needs to be replenished in time, so the plasma The colloid osmotic pressure is physically increased, and the extravascular blood is passively infiltrated into the capillaries. The extravascular lymph and tissue fluids are also expanded accordingly, thereby improving the rheological parameters of the blood and reducing the viscosity of the blood. Delayed dissolution, blood toxins reduced or disappeared. (2) urinary tract: detrusor contraction, sphincter relaxation, bladder emptying effect, showing diuretic swelling. Clinically, it can be used for abdominal bloating and urinary retention after surgery. (3) Vascular system: There are vasodilatation and dilation combined with diuretic effect, which can lower blood pressure, comfortable head, smooth blood circulation, blood stagnation, and hemorrhagic depression. (4) Eye: The pupil sphincter and ciliary muscle contract, shrinking the pupil, lowering the intraocular pressure, restoring eyesight, adjusting sputum (myopia), and partial comfort. (5) Gastrointestinal function: Increased contraction amplitude and tension, increased gastrointestinal secretion, and enhanced digestive capacity. N-like effect: (1) Exciting ganglia! ^Receptors, excite muscles, resist aging; (2) Excite the adrenal medullary N _M receptor, adrenaline, norepinephrine release; this effect can excite the β 2 receptor of bronchial smooth muscle, so that the bronchus does not shrink too much avoid causing respiratory adverse reactions; (3) the excitement of skeletal muscle _Ν Μ receptors: the performance of muscle contraction in the lesion site can establish a pinching effect of around efflux.

Clinical toxicology: Excessive can cause cholinergic crisis: (1) Stomach discomfort, slang words, generally do not vomit, no pain (stomach smooth muscle is too excited to contract). (2) The lower abdomen is longitudinal, ventral, and weak (intra-abdominal smooth muscle, abdominal wall muscle contraction). (3) Sudden general weakness, lower limbs can not move or paralyzed (reflective center is too excited, forming fasciculation, increased muscle weakness, conduction center upper and lower nerve pathways excitatory block, forming a reversible vertebral body bundle syndrome of about four hours) . (4) cold hands and feet (sputum-like effect, slow heart rate, heart block, heart temperature can not be extended by the extremities of the extremities). (5) sweating (the sympathetic post-ganglionic fibers are too excited to cause a large amount of sweat gland secretion). (6) chest tightness, chest pain, back pain, back pain, neck stiffness or body numbness pain (the skeletal muscles of the erector spinae are too contracted to stimulate the nerve roots, forming root pain, etc. Reaction). (7) Even breathing paralysis (breathing muscles and airway smooth muscles are too contracted and the respiratory center is too excited and then caused by inhibition, often occurs when a single dose exceeds the amount). (8) Excessive to abortion in pregnant women (caused by excessive contraction of uterine smooth muscle).

After taking the therapeutic amount for 10 days, the following effects may occur: (1) Head headband (the head skeletal muscle mainly composed of the frontal muscle of the occipital front is caused by the contraction of the scalp aponeurosis causing the scalp tightness); (2) In the long-term work, the middle finger is the first finger, the back is strong and slightly painful, and the toe is intermittently slightly painful (the finger back muscle and the tendon sheath are pulled, this effect is remindative, protective, therapeutic) (3) neck back (caused by erector spinae mainly caused by excitatory contraction of the back muscle) (4) one or two saliva can be swallowed or swallowed from the mouth during sleep (caused by healthy secretion of salivary glands) (5) calf wrinkles ( Increased renal function, bladder smooth muscle contraction, diuretic effect caused by sphincter relaxation) (6) The upper and lower eyelids are neurologically spurted for a while (the ganglion excitability causes nerve endings).

Motherwort extract: Motherwort granules, motherwort cream, motherwort syrup, motherwort oral solution, motherwort capsule, 茺蔚丸, 茺蔚油, 茺蔚散, 茺蔚冲, 茺蔚膏, 茺蔚 syrup, 茺蔚 oral solution The active ingredients of Yiwei capsule, Yimucao injection or its extracts, such as motherwort, motherwort, motherwort total alkaloid, motherwort A and stachydrine, are all acetylcholinesterase inhibitors.

Treatment and prevention of Alzheimer's disease, Alzheimer's disease, Parkinson's disease, rickets, schizophrenia. M-like effect, enhance the secretion of glands including hypothalamus and pituitary, so that the hormone levels in the body reach a unified balance of opposites, resisting neurological disorders. The medicament of the present invention is effective for treating Alzheimer's disease (AD), and has the functions of enhancing central cholinergic nerves, and slowing or stopping the formation of amyloid β-amyloid precursor protein (ΑΡΡ) fragments. Central role It can last for several months, which can improve the memory, understanding and behavior of AD patients, and at the same time facilitate the transfer of neuromuscular junctions. After clinical trials, the results are significantly reliable. N-like effect, the contraction of the frontal muscles of the forehead makes the upper part of the head form a tight-fitting effect, which can physically control abnormal brain activity, continuous contraction of skeletal muscle, and inhibition of pathological spastic contraction. Acetylcholinesterase inhibitors have good physiological functions in protecting dopaminergic neurons and improving PD dyskinesia. By inhibiting acetylcholinesterase to prevent neuronal apoptosis, the patient's dopaminergic neurons are protected, and the function of the nigrostriatal dopaminergic nervous system is enhanced: inhibition of acetylcholinesterase can also increase endogenous acetylcholine Concentration, which regulates the release of striatal dopamine through nicotinic cholinergic β 2 receptor, achieves the effect of treating both PD and PD, especially for PD patients with dementia. Clinically, 10 drugs of Alzheimer's disease, 6 cases of Parkinson's disease, 3 cases of rickets, and 10 cases of schizophrenia were treated with the drug of the present invention, and all of them achieved satisfactory effects.

Treatment of rheumatoid arthritis, systemic lupus erythematosus, myasthenia gravis, progressive muscular atrophy, varicose veins of the lower extremities, thromboangiitis obliterans, acne, psoriasis, vitiligo, and goose wind.

M-like effect, enhanced by neuromodulation and humoral regulation and self-regulation, balance of body hormone levels, abundant tissue fluid, reduction of endotoxin, fresh blood, enhanced immunity, alleviation of syndromes, lower extremity edema is the main cause of acne the reason.

Pathology: The central part of the limbs, the torso, the head surface of some pairs of nerves on the same section or adjacent to several sections, long-term loss of excitation (related to superior neurological factors), resulting in the corresponding nerve roots, nodes, tips The inflammatory reflexes diminish or disappear, causing their counterparts to lose their neurotrophic protection and dominance control. Symmetrical local functional waste lesions, referred to as symmetrical changes, pathologically reflected in the joints are rheumatoid arthritis, reflected in the facial systemic lupus erythematosus, reflected in the body's muscle weakness, reflected in the muscle spindle For progressive muscular atrophy, plus Exogenous wind, cold, dampness, heat, poison and labor injuries make the symptoms worse.

Pharmacology: M-like action, excitatory nerve exudation, reflex caused by afferent nerve movement, exercise strong reflex arc, so that the same organ where the receptor and effector are located, forming continuous excitement, local function improvement and recovery, inhibition The proliferation and atrophy of organ tissues, the activation of 2 receptors, the slow and long excitatory contraction of the back muscles of the fingers, toes and the back muscles of the spine, which promoted the recovery and enhancement of a series of physiological functions at the site, thereby improving Symptoms, reduced deformity. Due to the excitatory contraction of the back muscles, which are mainly erector spinae, this effect can treat spinal diseases such as cervical spondylosis, lumbar disc herniation and ankylosing spondylitis. Clinically, 33 cases of rheumatoid arthritis were treated, 15 cases of light patients with joint symptoms were relieved, 13 cases of moderate patients with joint symptoms disappeared, 5 cases of severe joints with different degrees of improvement; systemic lupus erythematosus 3 cases, of which 1 case was cured, 2 cases were relieved; 5 cases were treated with muscle weakness, progressive muscular atrophy, 20 cases of varicose veins of lower extremities, 5 cases of thromboangiitis obliterans, 5 cases of hemorrhoids, 15 cases of psoriasis, 15 cases of vitiligo, goose Six cases of palm wind achieved satisfactory results.

Treatment of hypertension, coronary heart disease, hyperlipidemia, cardiovascular and cerebrovascular diseases. Cholinergic excitatory, M-like effect, increase glandular secretion, increase or decrease of hormones and neurotransmitters, form a virtuous cycle of neuromodulation and humoral regulation in vivo, and enhance the blood purification function of the present invention. The toxic substances in the body are reduced or disappeared, the blood quality is improved, the enamel is ablated, the blood rheology is improved, the blood is moist and fresh, and the blood vessels are dilated, the blood circulation is smooth, and the blood is not smashed. The hemorrhagic disease stops, the blood disease is relieved and controlled, and the blood pressure is lowered by blood quality improvement, vasodilation, and diuretic effect. The M effect relaxes the coronary artery, and the heart rate is relieved at a level of about 80 beats/min, which reduces the cardiac load and improves the symptoms of myocardial ischemia and hypoxia. Motherwort, motherwort, motherwort total alkaloids, motherwort A, and stachydrine can improve myocardial blood supply, lower blood pressure, lower blood viscosity, inhibit platelet aggregation, anticoagulation, antithrombotic, and fibrinolysis. Cardioprotective effects: The production of a large number of free radicals and the lipid peroxidation induced by them are the main mechanisms of myocardial ischemia-reperfusion injury. Myocardial ischemia is caused by ligation of rabbit coronary arteries. Injection, compared with the control group after 10 minutes of treatment, found that Motherwort can significantly reduce the content of malondialdehyde (MDA) in myocardial tissue and enhance superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX). Activity, improving the ischemic manifestations of the ECG. It indicated that the active constituents of Leonurus extract could protect the activity of the antioxidant free radical enzyme system, inhibit the lipid reaction during myocardial ischemia and reperfusion, and alleviate myocardial cell damage caused by excessive oxygen free radicals.

Clinical use of motherwort, motherwort, motherwort total alkaloids, motherwort A, and stachydrine for the treatment of hypertension, a total of 214 cases, including 134 cases of primary hypertension, 52 cases of secondary hypertension, three high There were 28 cases of blood pressure, and the results were 132 cases, 40 cases, and 21 cases. The effective rates were 2 cases, 10 cases, and 4 cases. The ineffectiveness was 0 cases, 2 cases, and 3 cases. The effective rates are 100%, 96%, and 89%. The above results indicate that the therapy has a good effect on all stages of hypertension. And can relieve angina,

Lowering blood viscosity: 105 patients with blood hyperviscosity were treated with active ingredients of motherwort extract. Clinical symptoms such as dizziness, headache, insomnia and numbness were mostly alleviated. Blood rheology indicators such as whole blood specific viscosity (high cut and low cut), whole blood reduction specific viscosity (low cut) viscosity index, whole blood reduction specific viscosity (high cut), red blood cell deformability TK value, platelet aggregation rate, Both fibrinogen content and erythrocyte electrophoresis time were significantly improved, and the difference was significant before and after treatment (P <0.05). Inhibition of platelet aggregation, anticoagulation, antithrombotic, in vitro observation of active ingredients of Leonurus extract against platelet aggregation experiments showed that the active ingredient of Motherwort extract can maintain the platelet aggregation ratio of burned rats in the normal range, while the control group significantly reduced the ratio In the ice stress test, the pre-injection of motherwort alkaloids, the incidence of myocardial small blood vessel platelet aggregates in rats was significantly reduced. Rats after pre-injection of motherwort alkaloids were further instilled with adenosine diphosphate (ADP), and the incidence of platelets and their aggregates in the blood and alveolar wall capillaries was significantly reduced.

In addition, the active ingredient of Motherwort extract also enhances fibrinolysis, thereby inhibiting thrombus formation. The mother of the motherwort extract of the present invention is fed with the active ingredient preparation, and then blood is taken from the common carotid artery for blood coagulation measurement. The results show that the above preparation can inhibit platelet function, reduce internal and external coagulation function, and promote fibrinolytic activity. The formation of extracorporeal thrombosis. In the fibrinolysis experiment using urokinase-type plasminogen activator (ιι-ΡΑ) and tissue plasminogen activator (t-PA) to activate plasminogen, 20 kinds of traditional Chinese medicine for promoting blood circulation and removing blood stasis were observed. The effect on fibrinolysis showed that the extract of Motherwort had the strongest fibrinolytic activity.

Treatment of aplastic anemia, purpura and disseminated intravascular coagulation prevention. The M-like action of the active ingredient of the motherwort extract of the present invention has the effects of improving blood quality, blood circulation, improving the immunity of the body, and effectively controlling the symptoms of skin, mucous membrane and internal organs caused by it. The N-like effect causes the dorsal muscles of the erector spinae to excite and contract, and the central cholinergic nerves excite. The spine, nerve center and spinal cord form a series of functional improvements, which restore and strengthen the hematopoietic system and blood cell functions.

M-like blood quality improved, reducing the occurrence of purpura. In clinical application, 20 cases of aplastic anemia were treated with the drug of the invention, 17 cases were cured, 2 cases were obviously improved, 1 case was ineffective, the effective rate was 95%, and the cure rate was 85%. Clinical treatment of 60 cases of purpura, purpura phenomenon disappeared. For the prevention of disseminated intravascular coagulation (DIC), through more than 1,000 cases of birth control surgery in 3 years For clinical application, the drug of the present invention was administered three days before the operation, and no DIC symptom occurred in the operation room.

Treatment of menstrual irregularities: The application of motherwort extract as an acetylcholinesterase inhibitor has a strong excitatory effect on the uterus, which can enhance the amplitude, frequency and tension of uterine contractions. The active ingredient of the motherwort extract can make the rat uterus in the early stage of estrus change from a small amplitude irregular spontaneous contraction to a large amplitude regular contraction. The contraction can last for several hours, but it can be recovered after washing. The excitability of cholinergic nerve can enhance the secretion function of the largest glandular liver in the human body, increase the bioconversion rate, promote the toxicity reduction and excretion rate of toxic substances in the body, thus reducing the toxins and impurities in the blood. Increased fluids in certain parts including blood, especially in the blood vessels, improve blood quality, blood is fresh and flawless, and blood vessels are dilated, blood circulation is smooth, menstrual pain is relieved or disappeared, and uterine smooth muscle function The healthy contraction inhibits the permeability of the endometrial capillaries, so that the blood from the menstruation is not much more, and the amount of formation is moderate.

Treatment of tumors, leukemia: In the clinic, there is a case of a large egg with a large egg on the back of the ridge. After taking the motherwort extract for two weeks, the tumor shrinks by about one-third and becomes soft. Take February. The tumor disappeared afterwards. An elderly male with a large table tennis ball on the right eyebrow bone for more than seven years, taking the motherwort extract 茺油 oil twice a day, each time 2ml, gradually reduced after 5 days, after 2 months of tumor disappear. Clinically applied to the treatment of 10 cases of leukemia, can effectively control bleeding, improve symptoms. Through the use of motherwort extract: Yuwei Oil and Yimu Ointment for the clinical treatment of 30 cases of malignant tumors (including 10 cases of gastric cancer, 5 cases of lung cancer, 5 cases of liver cancer, 6 cases of breast cancer, 4 cases of uterine cancer), the conclusions are as follows:

(1) This drug preparation for treating tumor has a strong anti-tumor effect, and most of the cases in this group are In the advanced stage, the effective rate (PR+mR) was 42.9%, indicating that the growth of the tumor was inhibited, and if the course of treatment was prolonged, the effect could be increased.

(2) can significantly improve the patient's symptoms, fatigue, anorexia, symptom relief rate of 73.5% compared with the control group, there is a significant difference.

(3) It has obvious immunomodulatory effects and increases the patient's ability to resist disease.

Pharmacological analysis: (1) The concentration of acetylcholine is increased, and the M effect can increase or decrease the ratio of hormones secreted by all glands including pituitary and adrenal medulla to Ach, thereby achieving hormone and neurotransmitter pairs. The uniform balance of the interaction of cells enhances the protection and control of nerves on cells, thereby reducing the probability of cell mutation and mutation. (2) The relative balance between the ligands of the cell receptors can also inhibit the infiltration of the secretions of cancer cells into normal cells, thereby reducing the rate of cancer spread. (3) The enhancement of glandular secretion activity and the long-term continuous excitatory contraction of smooth muscle and skeletal muscle also reduce the space of the placeholder from the physical point of view and inhibit the development of the tumor. (4) Through the regulation of neuromodulation and humoral regulation and self-regulation, the homeostasis of the body's internal environment is consolidated and strengthened, the immunity is enhanced, and the reduction of toxins in the body is reduced, which fundamentally resists the occurrence and development of tumors.

Treatment of hepatitis B, jaundice hepatitis, cirrhosis. Clinically, the drug of the present invention has a good positive regulation effect on the human body, and the active ingredient of the motherwort extract on the mouse T lymphocyte activated by concanavalin A (conA) is indicated by the ³ H-thymidine intrusion method. It has a strong proliferative effect, and its effect is 5 to 8 times that of conA alone, indicating that it can enhance the cellular immune function of the body. In addition, the M-like action of the drug of the present invention increases the secretion of the liver gland, improves and strengthens the liver function, promotes its detoxification, metabolism, biotransformation speed and intensity, improves blood quality, blood circulation, and reduces portal hypertension and liver. Relaxation of the ampullary sphincter of the pancreatic ampulla, Reduce biliary obstruction, facilitate bile discharge; improve liver function, promote the early emergence of hepatitis B e-antibody, increase the negative rate, and choline substances can resist liver steatosis, diuretic effect can eliminate cirrhosis ascites, so there is treatment And prevention of hepatitis B and cirrhosis. Clinical treatment of 50 cases of hepatitis B, 73 cases of jaundice hepatitis, 21 cases of cirrhosis, have achieved good results.

Treatment of glaucoma, cataract, fundus hemorrhage, tinnitus, deafness, hair loss. Thirty-six patients with glaucoma were treated with oral administration of the drug of the invention for 15 days, 33 patients were markedly effective, 3 patients were effective, and 0 patients without hypotension, with an effective rate of 100%. There were 30 cases of cataract, 11 cases recovered, 16 cases improved symptoms, and 3 cases were ineffective. The treatment of 13 patients with fundus hemorrhage can basically eliminate the symptoms in about 20 days. The neuromodulation effect of the medicament of the present invention can have a significant therapeutic effect on functional tinnitus and deafness, stimulation of cholinergic nerves, improvement of sensitivity of the auditory nerve in the vestibular volute, and improvement of auditory function. In the clinical treatment of 53 cases, their symptoms disappeared. It has obvious inhibitory effect on fat-soluble alopecia, neuro-alopecia and vegetative alopecia. The mechanism is that the skeletal muscle contraction of the occipital skeletal muscle, which is mainly based on the frontal muscle, causes the scalp tightness to increase the scalp tightness and enhance the utilization of local nutrients. The enhanced synthesis of germinal substances and the enhanced function of the spleen are related to the enhanced function of the germinal center in the spleen. By the action of the M-like effect on the eye and the action of vitamin A substances, the intraocular pressure can be lowered, the metabolism of the eye can be accelerated, the absorption of blood in the fundus can be promoted, and the vision can be restored and strengthened.

Treatment of nephritis, uremia. M-like effect, vasodilation makes the renal capillaries smooth, the glomerular filtration rate increases, and the diuretic effect of the bladder, so that the urine excretion is smooth, the edema subsides, the blood rheology index of the drug is improved, and the blood endotoxin is improved. Reduced, can effectively inhibit hematuria. Gland secretion causes liver function to be strong, liver blood is improved, blood toxins that enter the kidney are reduced, thereby reducing the stimulation and destruction of toxic substances on the kidneys, while the sympathetic nerves are excited and stimulated. Recovers kidney function, protects nephron, corrects metabolic acidosis, and resists uremia. Motherwort extract has a certain preventive effect on acute tubular necrosis (ATN) in the initial stage; it has protective effect on the kidney during the occurrence and development of acute renal failure caused by gentamicin; acute in rabbits caused by glycerol physiological saline Renal failure significantly increases renal cortical blood flow, improves renal function, reduces or restores renal tubular cell degeneration, turbid swelling and other pathological changes, with creatinine (cr), urea nitrogen (BCIN), filtered sodium excretion fraction (EFNC) Renal blood flow (RBF) and animal survival were used as indicators to demonstrate that the active ingredients of Leonurus extract have significant effects in the treatment of nephritis, uremia and renal failure. Clinically, 72 patients were treated with the drug of the invention, including 39 males and 33 females, aged 6-81 years old, and 47 patients aged 50 years and older. The effects were as follows: 43 cases of chronic nephritis, including: 25 males, female 18 cases, effective and markedly effective in 42 cases, ineffective in 1 case; 23 cases of acute nephritis, including: male 15 cases, female 8 cases, 8 cases cured in one course (15 days), 11 cases cured in two courses, three courses cured 4 For example, there were 7 cases of uremia, including 5 males and 2 females, 3 cured, 2 improved, and 2 unexplained. The above data indicates that the total effective rate of the motherwort extract of the present invention for treating acute and chronic nephritis and uremia is 95.83%.

Treatment of prostatitis, benign prostatic hyperplasia, and enlarged prostate. The M-like action of the medicament of the present invention can enhance the secretion of prostate function, stimulate the contraction of gland smooth muscle, inhibit the proliferation of prostate, hypertrophy, and improve and eliminate a series of symptoms such as urinary abnormality.

After a course of treatment for prostatitis and benign prostatic hyperplasia with the above drugs, in the 56 cases, 19 cases were cured recently, 29 cases were markedly effective, 7 cases were effective, 2 cases were ineffective, and the total effective rate was 96.43%. During the period, all cases were examined by B-ultrasound before and after treatment to determine the changes in prostate size (cm ³ ) and residual urine volume (ml). The results show that the prostate volume shrinks and residual urine volume There was a significant difference between the reduction and the pre-treatment (P < 0.01). The specific results are shown in the following table:

Clinical treatment showed that: Motherwort extract has significant curative effect on prostatitis and benign prostatic hyperplasia and hypertrophy, which can reduce inflammation, inhibit fibrous tissue proliferation, increase local blood flow, significantly improve clinical symptoms of patients, and reduce the size of prostate. Improve a series of symptoms of urination.

Treatment of diabetes insipidus and diabetes. Pharmacology: M-like effect, the upper gland of salivary gland is more secreted and the mouth is not thirsty. Continuous stimulating contraction of gastrointestinal smooth muscle, resulting in shrinking gastrointestinal space, physical inhibition of food intake, recovery and enhancement of renal medulla secretion function, recovery and improvement of renal tubular concentrating function, and balance regulation of hormone secretion in pituitary gland The urine volume of diabetes insipidus and diabetes can be reduced; the ganglion is excited, the effect function of the target cells acting on insulin is restored, the chance of insulin resistance is reduced, the source of blood sugar is reduced, and the path is increased, thereby lowering blood sugar level. Parasympathetic postganglionic fiber excitement, promote insulin secretion, improve sugar absorption and utilization; N ₂ receptor excitation, muscle paralysis caused by diabetes subsides, limb sensation recovery; M-like effect can restore eyesight caused by diabetes.

Typical case: When a middle-aged woman goes downstairs, she accidentally stepped on the air and flipped it over the stair railing. After a few minutes, she rescued herself. After a week, she had a big thirsty drink, drinking four or five tea bottles during the day and drinking three at night. Four teas of water, the spirits are weak, the tongue is gradually blackening and thickening, each bowl of liquid rice is eaten, and the salty rice is not eaten for several months, but it needs to eat a lot of fruits every day. After many inspections, no results, run many Hospital treatment is invalid, extended to more than half a year, taking this medicine for more than ten days, the condition is basically paralyzed More. In the clinic, 7 cases of diabetes insipidus were treated with the drug of the invention, 3 cases were cured, 3 cases were markedly effective, and 1 case was inaccurate.

The results of the clinical trial of taking the drug of the present invention for clinical treatment of diabetes:

The test statistics showed that: 74 patients with diabetes were treated with the agent of the present invention, 74% of which achieved significant effect, 23% of which were basically effective, 3% of ineffective, and 97% of total effective rate.

Treatment of gastroptosis, uterine prolapse, drooping eyelids: sagging disorders are mostly caused by ligament relaxation or decreased muscle tension, Chinese medicine believes that the lack of gas in the system, caused by qi deficiency. The M-like action and the N-like action of the medicament of the present invention can cause contraction of the gastric smooth muscle, contraction of the uterine smooth muscle, excitation of the superior and inferior phrenic nerves, restoration of normal neuromodulation function, and restoration of the organ tissue in situ. Clinical treatment of 33 cases of gastroptosis, 27 cases of uterine prolapse, 9 cases of drooping eyelids. Both completely or substantially completely reset the sagging organs or tissues.

Treatment of hyperthyroidism, spleen disease:

The drug of the present invention forms a balance between hormones and functions secreted by the thyroid gland and the parathyroid gland through neuromodulation and humoral regulation, inhibits hyperthyroidism, supports hypotony, positively regulates, and acts dually to achieve high metabolism caused by thyroxine. Rate and exophthalmia symptoms, M-like effect makes the spleen smooth muscles excite and contract, inhibits spleen enlargement, through humoral regulation, blood rheology refers to The target is improved, the corresponding lymph fluid production is increased, the normal function of the spleen is improved and restored, the immune response ability of the spleen is improved, the platelet accumulation in the spleen and the autoimmune hemorrhagic reaction thus occurring are relieved. Clinical treatment of 70 cases of hyperthyroidism, 11 cases of splenomegaly, have achieved significant results.

From the above results, it can be concluded that the advantages of the present invention are:

1. The present invention has opened up a new application field by excavating new medical uses for the motherwort extracts such as oyster sauce, motherwort cream, motherwort syrup, motherwort granules, motherwort oral liquid, and motherwort capsules.

2. The active ingredients of motherwort extract, motherwort, motherwort, motherwort total alkaloid, motherwort A, and stachydrine are all acetylcholinesterase inhibitors, safe and non-toxic, and have strong pharmacological effects, indicating good medicinal prospects. .

3. The material of the invention has rich source and low cost, simple preparation process, and can be prepared into an oral dosage form, a syrup, an injection form, a tablet, a capsule type, an oil agent, a dropping pill, a granule, etc., and is convenient to use.

4. The medicament prepared by the substance of the invention has the remarkable use of the acetylcholinesterase inhibitor drug of the cholinergic medicine, and can treat and prevent Alzheimer's disease, rickets, schizophrenia, rheumatoid arthritis, psoriasis, vitiligo , goose palm wind, systemic lupus erythematosus, hypertension, cardiovascular and cerebrovascular diseases and other diseases. The most important feature of the invention is that it not only makes the adjustment of the lesion more prominent, but also makes the overall adjustment close to perfection.

5. Use of the substance of the invention as an additive. If added to milk powder or edible oil, it can supplement a variety of amino acids, trace elements and vitamins required by the human body, and can be completely compatible with various oils and fats. The effective active ingredients contained in the oil are not easily destroyed by high temperature, and have a flavor, Good taste, suitable for both medicine and food. Has eyesight, glory, suppresses tinnitus, reduces eye bags, reverses degenerative camel Back bending, inhibiting the relaxation and degenerative aging of organs such as the gastrointestinal, uterus and skeletal muscles, can positively regulate the body's functions, enhance the body's immunity, prevent the occurrence and development of many diseases, improve the sub-health state, prolong life and strengthen the body. Improving the utilization rate of food digestion, improving people's cognitive memory, and improving human health, its application has a positive impact on reducing social medical expenses. If it is added to rubbing cosmetics, washing daily necessities, oral care daily necessities, it can make the touched skin rosy and beautiful. This phenomenon is beneficial to the expansion of blood vessels, smooth blood circulation, and partial blood-rich M-like pharmacological effects. The N-like effect excites the skin muscles and inhibits the skin's regression and aging. At the same time, the effect of the peri-contraction and pinching of the drug in the lesion site can obviously control and eliminate the skin damage caused by diseases such as spots, rashes, sputum and sputum. Acting on the oral cavity, it can enhance the secretion of oral glands, fill the oral blood, keep the mouth moist and not dry, facilitate the exchange of substances in the periodontal matrix, enhance the timely supply of nutrients required by the teeth, strengthen the dentin, and accelerate The elimination of toxic substances in the roots of the teeth inhibits ulceration of the oral mucosa and reduces dental disease. It can also make the muscle smooth muscle of the gums excite and contract, stabilize the teeth and prevent the teeth from loosening. BRIEF DESCRIPTION OF THE DRAWINGS:

Figure 1 shows the percentage of inhibition of hAChE by water extract of Motherwort

Figure 2 shows the percentage inhibition effect of active ingredients of Motherwort on hAChE

Figure 3 shows the percentage of inhibition of hAChE and hBChE by motherwort base.

Figure 4 shows the percentage inhibition of AChE and BChE by motherwort.

Figure 5 shows the percentage inhibition of AChE and BChE by total alkaloids of Motherwort

Figure 6 shows the percentage inhibition of AChE and BChE by motherwort A.

Figure 7 shows the percentage inhibition of AChE and BChE by stachydrine.

Figure 8 MTT cytotoxicity assay of active constituents of Motherwort extract on NIE-115 Fig. 9 MTT cytotoxicity detection of active ingredients of Motherwort extract on SHSY5Y

Example 1: Preparation of Motherwort Water Extract

1000 g of motherwort was purchased from a market pharmacy, and the motherwort whole grass was boiled under reflux in 3000 ml of distilled water for 45 minutes, the cooked extract was filtered, and then the filtrate was freeze-dried, and the freeze-dried product in the form of powder was weighed to 50 g.

Example 2 Preparation of Motherwort Water Extract

In the market Chinese medicine pharmacy, there is a motherwort cream sold, and the motherwort cream is dissolved in steamed water, stirred, filtered, and the filtrate is freeze-dried to form a motherwort water extract.

Example 3 Preparation of tablets

Using motherwort 0.5 _g , corn starch 95. 5 g, magnesium stearate 4 _g , all the components were uniformly mixed and made into 100 pieces. Each tablet contains 5 m _{g of} motherwort base.

Example 4 Preparation of tablets

Using 0.5 _{g of} motherwort, 95.5 _{g of} corn starch, and 4 _{g of} magnesium stearate, all the components were uniformly mixed and made into 100 pieces. Each tablet contains 5 m _{g of the} motherwort component.

Example 5 Preparation of Capsules Containing Yuwei Oil

The capsule containing oyster sauce is prepared by pressing the motherwort (茺蔚子) into oil, and filtering to obtain oyster oil, and each soft gelatin capsule is filled with lml oyster oil to prepare oyster oil capsule.

Example 6 Motherwort Sulfate Oral Liquid (dose with tablet)

Proportion of raw materials: 5m _g / piece as an example

Motherwort sulphate (calculated as motherwort) 5 _g , sucrose 100 _g , citric acid 20 _g , appropriate amount of essence, distilled water 5000 ml, made into 1000, take distilled water, the amount of prescription Add the auxiliary material to the water, stir and dissolve, filter, continue the filtrate and add distilled water to 5000ml, add the essence, stir evenly, sub-package, each 5ml, gland, 100'C, disinfection for 1 hour, check and pass. Example 7 injection (0.5, 1, 1.5, 2.5, 5, 10, 20 mg / support)

The following is an example of the specification of 5m _g / branch: Motherwort sulfate (calculated as motherwort) 5 _g , 5000 ml of water for injection, 1000 pieces. Dissolve the prescribed amount of motherwort sulphate in water for injection, add 0.3% of the needle to the activated carbon, stir for 30 minutes, decarbonize, sterilize and filter (0.22 rn microporous membrane), and dispense under sterile conditions. Melt seal, each 5ml, 100'C sterilization for 1 hour, check, that is.

Example 8 dry powder needle (specification with injection)

Proportion of raw materials and auxiliary materials: Take 5m _g / branch as an example. Leonurine sulfate (calculated by Leonurine) 5g, mannitol 95 _g, 1,000 made lyophilized. Take the prescribed amount of motherwort sulphate and mannitol, add appropriate amount of water for injection, control the pH value between 4.0~6.5, add water for injection to 1000ml, mix the hook, add 0.3% needle and stir with activated carbon for 30 minutes, decarbonize , sterile filtration (0.22 m microporous membrane), sub-packaged under aseptic conditions, each lml, freeze-dried into a white block or powder, that is.

Example 9 as a food product such as an edible oil additive

The ratio of raw materials and auxiliary materials: On蔚油 lOnil, edible oil 5000ml, add oyster oil to the edible oil and stir to form a health-care edible oil.

Example 10 as a food product such as an edible oil additive

The ratio of raw materials and auxiliary materials: On蔚油 lOnil, edible oil 300ml, add oyster oil to edible oil and stir to form a health-care edible oil.

Example 11 was made as a food product such as an edible oil additive The ratio of raw materials and auxiliary materials: 10ml of oyster sauce oil, 500ml of edible oil, adding oyster oil to edible oil for stirring, it is a health-care edible oil, which can be applied to the recovery of uterine function during pregnancy, accelerate the elimination of stagnation, and alleviate Pain after childbirth can also promote the elimination of pregnancy spots.

Example 12 as a rubbing cosmetic additive

Rubbing cosmetics such as moisturizing lotion, anti-wrinkle milk, mask, etc. The active ingredient of motherwort extract, oyster oil or motherwort extract is added as an additive to the preparation of anti-wrinkle milk.

Preparation of raw materials and auxiliary materials: 100 grams of oyster oil and 15 grams of sodium decyl sulfate are mixed, stirred and mixed for use. In addition, 10 g of vitamin C and 10 g of vitamin E and 0.1 g of ethyl p-hydroxybenzoate were added to 600 g of distilled water to dissolve. Finally, the two solutions prepared above were mixed, and emulsified by thorough stirring, and 0.1 g of the essence was added, and stirring was continued to obtain.

Example 13 as a washing-type commodity additive

Washing daily necessities such as shampoo, soap, shower gel, etc. The active ingredient of motherwort extract, oyster oil or motherwort extract is added as an additive to the preparation of shampoo.

Preparation of each raw material ratio: (1) Dissolve 3 g of calcium pantothenate in 70 g of water, stir until fully dissolved, and use. (2) 80 g of triethanolamine lauryl sulfate, 30 g of fatty acid diethanolamine, 0.2 g of formaldehyde (40% solution), and 3 g of hyaluronic acid were added to the solution prepared in the step (1), and stirred and uniformly mixed. (3) Dissolve 2 g of dragon grass oil and 1 g of stachydrine in ethanol, mix well, pour into the solution prepared in step (2), stir and mix to obtain the finished product.

Example 13 as an oral care-type daily necessities additive

Oral care daily necessities such as mouthwash, tooth powder, toothpaste, chewing gum, etc. The active ingredient of the motherwort extract 茺油 oil or motherwort extract is added as an additive to the preparation of the mouthwash. Preparation of raw materials: 1 g of lemon oil, 1 g of perilla oil, 1 g of clove oil is dissolved in 100 g of ethanol, and then 1 g of motherwort and 800 g of distilled water are mixed with the above substances, and cleaned. The glass rod is mixed and evenly mixed to obtain the finished product.

Claims

Claim

1. The use of motherwort extract as an acetylcholinesterase inhibitor drug for cholinergic drugs, characterized in that: motherwort extract, motherwort granules, motherwort cream, motherwort syrup, motherwort oral solution, motherwort capsule, 茺蔚丸, 茺蔚Oil, 茺散散, 茺冲冲、, 茺膏茺, 茺糖 syrup, 茺口服 oral liquid, 茺胶囊 capsule, motherwort injection as a choline acetylcholine esterase inhibitor.

The use of the motherwort extract according to claim 1, wherein the main active ingredient of the motherwort extract is motherwort base, motherwort, and motherwort total A base, a parenteral base A, a stachysine or a pharmaceutically acceptable salt thereof is used as an acetylcholinesterase inhibitor of a cholinergic agent.

The use of the motherwort extract according to claim 1 as an acetylcholinesterase inhibitor drug of a cholinergic agent, characterized in that: the main active ingredients of the motherwort extract, motherwort base, motherwort, motherwort total base, motherwort A mixture of a base a, a stachysine or a pharmaceutically acceptable salt thereof or a mixture of the two as an acetylcholinesterase inhibitor of the cholinergic.

The use of the motherwort extract according to claim 1 as an acetylcholinesterase inhibitor drug for a cholinergic agent, characterized in that: the main active ingredient of the extract of the scorpion scorpion, the motherwort, the stacolin Or a pharmaceutically acceptable salt thereof as an acetylcholinesterase inhibitor of a cholinergic agent.

The use of the motherwort extract according to any one of claims 1 to 4 as an acetylcholinesterase inhibitor drug of a cholinergic agent, characterized in that the motherwort extract is used as an acetylcholine ester of a cholinergic drug. Enzyme inhibitors in the preparation of treatment and prevention: Alzheimer's disease, Alzheimer's disease, Parkinson's disease, rickets, schizophrenia, rheumatoid arthritis, systemic lupus erythematosus, muscle weakness, progressive muscular atrophy, varicose veins of the lower extremities, thromboangiitis obliterans, acne, silver Psoriasis, vitiligo, goose wind, hypertension, coronary heart disease, hyperlipidemia, cardiovascular and cerebrovascular disease, aplastic anemia, purpura, disseminated intravascular coagulation, irregular menstruation, tumor, leukemia, hepatitis B, yellow Biliary hepatitis, cirrhosis, glaucoma, cataract, fundus hemorrhage, tinnitus, deafness, alopecia, nephritis, uremia, prostatitis, benign prostatic hyperplasia, prostatic hypertrophy, diabetes insipidus, diabetes, ptosis, uterine prolapse, drooping eyelids, The application of drugs for hyperthyroidism and spleen disease.

6. Use of a motherwort extract according to claim 5 as an acetylcholinesterase inhibitor drug for a cholinergic agent, characterized by a method for treating and preventing a disease, comprising administering to a patient an effective therapeutic amount of an active ingredient to a patient The active ingredient is selected from the group consisting of motherwort base, motherwort, motherwort total base, motherwort A, stachydrine or a mixture thereof or a pharmaceutically acceptable salt thereof, or a mixture of the two.

The use of the motherwort extract according to claim 6, as an acetylcholinesterase inhibitor drug of a cholinergic agent, characterized in that the active ingredient is: motherwort base, motherwort, motherwort total base, and motherwort A , a mixture of stachysine or a mixture thereof or a pharmaceutically acceptable salt thereof or a mixture of the two together with an adjuvant to form tablets, capsules, injections, oral liquids, syrups, powders, ointments, oils, pills, granules Agent.

The use of the motherwort extract according to claim 6, as an acetylcholinesterase inhibitor drug of a cholinergic agent, characterized in that the effective therapeutic dose is 0.005-0.4 mg/kg·day of the active ingredient per day. Dosing.

9. The motherwort extract according to claim 6 as an acetylcholine ester of a cholinergic drug The use of the enzyme inhibitor drug is characterized in that: the active ingredient of the motherwort extract 茺蔚油 or motherwort extract is added as an additive to food or edible oil or rubbing cosmetics or washing daily necessities or oral care daily necessities.

The use of the motherwort extract according to claim 9, as an acetylcholinesterase inhibitor drug of a cholinergic agent, characterized in that the ratio of the additive to the additive is 1/5000-1/10 o