CN109498771B - Targeting composition for improving mild cognitive dysfunction and preparation method thereof - Google Patents
Targeting composition for improving mild cognitive dysfunction and preparation method thereof Download PDFInfo
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
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- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/16—Ginkgophyta, e.g. Ginkgoaceae (Ginkgo family)
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
- A61K36/815—Lycium (desert-thorn)
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
- A61K36/9062—Alpinia, e.g. red ginger or galangal
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
Abstract
The invention belongs to the technical field of medicines, and particularly relates to a targeted composition for improving mild cognitive dysfunction and a preparation method thereof.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a targeted composition for improving mild cognitive dysfunction and a preparation method thereof.
Background
Mild Cognitive Impairment (MCI) generally refers to various degrees of Cognitive decline caused by various causes. It is a clinical state intermediate between normal aging and dementia.
Mild cognitive dysfunction short (MCI) is a prodromal stage of alzheimer's disease, senile dementia (AD). Approximately 10-15% of patients with MCI may progress to conversion to AD each year; about 80% of the years have been converted to AD, and thus MCI is a high risk factor for developing AD.
The incidence of MCI is closely related to age. Epidemiological investigation shows that the number of AD people in China is 1000 million, the prevalence rate is 5.0-7.0% in people over 65 years old, and 1/3 in people over 80 years old may suffer from AD. The incidence of AD is reported to be 3-8% abroad.
MCI disease is manifested reversibly. MCI patients generally do not affect daily life, and the process appears to be reversible, remaining stable or reversing to a healthy state over time. Unfortunately, 10-15% of the exacerbations become severe AD that is difficult to reverse.
China is a big population country and is also an aging population country in the world. The population of the elderly by the end of 2017 years has reached 2.4 billion. How to prevent and treat diseases of aging population in the health field becomes a problem of high social concern.
AD is a disease difficult to diagnose and treat, no ideal therapeutic drug is found at present, heavy mental and economic burden is brought to patients, families and society, the economic burden of AD reaches 8180 billion dollars in 2015 throughout the world, and the AD is a very realistic social problem for the aging society. Chinese patent application No. 201611194946.1 discloses a composition for improving AD cognitive dysfunction, which comprises blueberry extract, ginkgo biloba extract, vitamin B6, vitamin B12, vitamin E, vitamin C, folic acid, docosahexaenoic acid, tea polyphenol extract, zinc lactate and selenium yeast.
According to the characteristics of the MCI development process, early discovery and early nutritional intervention are generally advocated, the MCI is improved as early as possible, the cognitive function of the old is improved, and the memory and learning and memory functions are improved, so that the prevention of AD is delayed.
There are many factors affecting mild cognitive impairment, and the results of foreign survey reports are inconsistent due to lack of uniform standards. The most common clinical criteria at present are those proposed by Petersen et al in 1999 (1) complaints of memory decline confirmed by informed persons; (2) objectively examining cognitive impairment that does not match age and education; (3) normal overall cognitive function; (4) preserving the daily life capacity; (5) not meeting the diagnosis standard of dementia. Studies have shown that MCI is a high risk group for dementia and converts to AD at a rate of 10% to 20% per year. Therefore, treatment of MCI is considered to be an important stage in the prevention and treatment of senile dementia.
The traditional Chinese medicine for preventing and treating mild cognitive impairment, Zhangtianli, Anhongmei, a journal of Chinese traditional medicine, No. 33, No. 2, 2015 for 2 months, researches the application of the Chinese herbal medicines in preparing mild cognitive impairment, researches that the traditional Chinese medicines such as radix polygoni multiflori preparata, herba epimedii, ginseng and the like or components thereof can improve the symptoms of cognitive impairment, and the traditional Chinese medicine compound has the following components: naokang No. II decoction (composition: radix polygoni multiflori preparata, radix rehmanniae preparata, pseudo-ginseng, calamus and polygala tenuifolia), yiqiaozhi sharpleaf galangal decoction (25 g of poria cocos, 15g of rhizoma acori graminei, 10g of prepared pinellia ternate, 6g of dried orange peel, 15g of codonopsis pilosula, 15g of prepared fleece-flower root, 15g of prepared rehmannia root, 15g of sharpleaf galangal fruit, 20g of arisaema cum bile and 3g of honey-fried licorice root), phlegm-reducing and resuscitation-dredging decoction, lipid-lowering and intelligence-improving granules, coptis chinensis gallbladder-warming decoction and brain-refreshing liquid.
In recent years, the cost of AD drugs is measured in tens of millions of dollars through global research and development, but the failure rate accounts for 99.6%, no new drugs are available on the market in the past 16 years, and only four symptomatic drugs which cannot be used for treating the cause are available at present.
Why developed modern medicine development does not find AD effective drugs? This is the single target point for traditional mainstream drug design, and MIC and AD are not considered to be caused by multiple etiologies.
Disclosure of Invention
The invention aims to provide a targeted composition for improving mild cognitive impairment and a preparation method thereof.
The targeted composition for improving mild cognitive dysfunction comprises, by weight, 20-30% of L-carnitine, 15-30% of fructus alpiniae oxyphyllae extract, 10-30% of ginkgo leaf extract, 10-30% of herba semiaquilegiae extract, 0.005-0.02% of cyanocobalamin, 0.01-0.03% of L-5-methyl-tetrahydrofolic acid and 10-30% of auxiliary materials.
Preferably, the composition comprises, by weight, 25-30% of L-carnitine, 20-25% of fructus alpiniae oxyphyllae extract, 10-20% of ginkgo leaf extract, 10-20% of herba semiaquilegiae extract, 0.005-0.02% of cyanocobalamin, 0.01-0.03% of L-5-methyl-tetrahydrofolic acid and 15-25% of auxiliary materials.
The L-carnitine comprises L-carnitine tartrate, L-carnitine fumarate or acetyl L-carnitine salt.
The preparation method of the extractive of the semiaquilegia root comprises the steps of drying and crushing the tender leaf of the semiaquilegia root to obtain semiaquilegia root powder, mixing the semiaquilegia root powder, water and glycyrrhizin, wherein the weight ratio of the semiaquilegia root powder, the water and the glycyrrhizin is 100: 500: 700: 0.2-1; soaking at 50-70 deg.C, microwave extracting, separating, concentrating, and drying to obtain herba Sedi Aizoon extract.
The invention compares the influence of different content of glycyrrhizin on the extraction rate of the Tianjing grass extract, and concretely refers to the table 1.
TABLE 1 Effect of glycyrrhizin on the extraction yield of Tianjing grass extract
The preparation method of the fructus alpiniae oxyphyllae extract comprises the steps of mixing fructus alpiniae oxyphyllae powder, water and glycyrrhizin, wherein the fineness of the fructus alpiniae oxyphyllae powder is 80 meshes, and the weight ratio of the fructus alpiniae oxyphyllae powder to the water to the glycyrrhizin is 100:500-700: 0.2-1; soaking at 50-70 deg.C, microwave extracting, separating, concentrating, and drying to obtain fructus Alpinae Oxyphyllae extract.
The invention compares the influence of different content of glycyrrhizin on the extraction rate of sharpleaf galangal fruit extract, and concretely shows that the content of glycyrrhizin in the sharpleaf galangal fruit extract is shown in Table 2
TABLE 2 Effect of glycyrrhizin on the extraction yield of Alpinia oxyphylla extract
The preparation method of the ginkgo leaf extract comprises the steps of mixing ginkgo leaf powder and water, wherein the weight ratio of the ginkgo leaf powder to the water is 1:5-20, and decocting to obtain the ginkgo leaf extract.
The glycyrrhizin is from traditional Chinese medicine liquorice, the liquorice is a traditional Chinese medicine prescription, "monarch, minister, assistant and guide", plays the role of a messenger "in compatibility, is beneficial to the performance of medicine properties, has the functions of reducing blood fat and detoxifying, and is safe and nontoxic.
Most of the existing surfactants are only used for in vitro detergents, and even safe sodium dodecyl benzene sulfonate has certain potential risks. The invention can obviously improve the extraction rate, and can improve the extraction rate by 22.12 to 97.05 percent within the range of 0.2 to 1.0 percent.
The preparation method of the fructus alpiniae oxyphyllae extract is a preparation method of extracting the fructus alpiniae oxyphyllae extract by using surfactant glycyrrhizin in cooperation with microwave. The preferable technical parameters of the extraction conditions are as follows: the powder fineness is 80 meshes, the solid-liquid ratio is 1:5, the dosage of the surfactant is 0.2-1.0%, the extraction time is 25min, and the microwave power is 300 w. Centrifuging to separate the third-stage extractive solution, vacuum concentrating and drying to obtain fructus Alpinae Oxyphyllae extract.
The preparation method of the extractive of the semiaquilegia root is a preparation method of the extractive of the semiaquilegia root by using surfactant glycyrrhizin to cooperate with microwave, and the preferred technical parameters of the extraction conditions are as follows: the powder fineness is 20 meshes, the solid-liquid ratio is 1:7, the dosage of surfactant glycyrrhizin is 0.2-1.0%, the extraction time is 20min, and the microwave power is 200 w. Centrifuging to separate the third-stage extractive solution, vacuum concentrating, and drying to obtain herba Sedi Aizoon extract.
The auxiliary materials are one or more of calcium hydrophosphate, hydroxymethyl propyl cellulose, liquid paraffin, silicon dioxide and magnesium stearate.
The invention also provides a preparation method of the targeted composition, which comprises the following steps of mixing the L-carnitine, the sharpleaf galangal fruit extract, the ginkgo leaf extract, the semiaquilegia root extract, the cyanocobalamin, the L-5-methyl-tetrahydrofolic acid and auxiliary materials, granulating and preparing tablets or capsules. The preferable steps are that cyanocobalamin, L-5-methyl-tetrahydrofolic acid, calcium hydrophosphate and hydroxymethyl propyl cellulose are mixed, dried and granulated; mixing fructus Alpinae Oxyphyllae extract, herba Veronicastri extract, folium Ginkgo extract and ethanol solution, drying, and granulating; mixing L-carnitine and liquid paraffin, and granulating; and finally, mixing the three granules, adding proper auxiliary materials, and preparing the tablets or capsules.
1. L-carnitine:
the brain neurotransmitter, levoacetylcholine, is the most basic substance for the functioning of the palm in memory and cognition. The human body has the function of synthesizing and manufacturing the substance, but the self synthesis capability of the human body is reduced after the middle-aged 45 years old, so that the cholinergic is reduced and lost, the memory is reduced, and then the level of the human body is lower and lower in the body due to the reduction of the liver and kidney functions, and the memory is declined to cause mild cognitive impairment.
Therefore, the acetylcholine donor, L-carnitine, must be supplemented as early as possible to ensure that memory impairment due to old acetylcholine deficiency does not occur.
L-carnitine has a chemical structure very similar to that of acetyl L-choline and is easily converted into acetylcholine in human body. L-carnitine has therefore been called acetylcholine precursor or acetylcholine donor. However, the supply of acetylcarnitine precursor is not enough, and the acetylcholine generated by the conversion of the acetylcarnitine precursor is easily destroyed by cholinesterase in vivo, so a protective agent should be matched.
The experiment of the invention shows that the L-carnitine can improve the learning and memory ability of the old animals, the L-carnitine can improve the function of mitochondria for generating energy, and the physical strength is recovered to make people in a light state. The L-carnitine also has the function of detoxification, and can transport and eliminate waste toxins generated after fat is burnt by mitochondria to outside cells to achieve the effect of detoxification.
2. Fructus alpiniae oxyphyllae extract: the sharpleaf galangal fruit is one of the traditional Chinese medicines for benefiting intelligence and strengthening brain in China, has the functions of warming kidney, securing essence, reducing urination, wetting spleen, stimulating appetite and absorbing saliva, and has the effects of benefiting intelligence and strengthening brain proved by the discovery of various active ingredients such as sesquiterpenes and flavonols contained in the sharpleaf galangal fruit through modern pharmacological research in recent years.
The current research shows that cognitive dysfunction and senile dementia are related to the increase of the activity of acetylcholine lipase in organisms, and the enzyme can hydrolyze acetylcholine, so that the acetylcholine level in vivo is reduced, and acetylcholine deficiency and central nervous system dysfunction are caused, thereby the learning, memory and cognitive dysfunction appear.
The invention discovers that the fructus alpiniae oxyphyllae extract has great value for improving MCI. It may inhibit acetylcholinesterase, and has cholinesterase inhibitor effect, so as to raise acetylcholine level and improve cognitive function.
3. Extractive of Tianjing grass: the herba Geranii is tender leaf (commonly called herba Geranii) collected from deciduous shrub of Lycium of Solanaceae in spring. The compendium of materia medica records that it has the functions of relieving restlessness, benefiting intelligence and tonifying five consumptions and seven impairments; strengthening heart-qi; remove wind in bone and joints, clear away heat and toxic material. Dispelling swelling of sores, dispelling wind and improving eyesight. Modern nutrition studies contain abundant nutritional ingredients: comprises protein, amino acid, mineral iron and trace element zinc; modern pharmacological studies contain a variety of active ingredients: including alkaloids, flavonoids, terpenes, steroids, etc. However, the influence of betaine, an alkaloid contained in the compound, on the human body's cognition is lacking in research, and in recent years, the betaine is found to reduce homotype cysteine level and improve HCY.
Hyperhomocysteinemia (hyperhomocystin leveisis HHCY), a recognized risk factor for cognitive dysfunction in the elderly. Adverse manifestations of high HCY include promotion of cognitive decline, resulting in oxidative damage to brain tissue, and neurotoxic effects on neural excitotoxicity; promoting brain cell apoptosis; promoting atherosclerosis; affecting nerve conduction function, and accelerating MCI process to form senile dementia.
It was found by the methionine conversion process in vivo that homocysteine produced in the absence of nutrients (methylated betaine, methyltetrahydrofolate, vitamin B12) could not be converted into the beneficial antioxidant glutathione and the beneficial S-adenosylmethionine (active methyl donor). Therefore, the above-mentioned deficient nutrient components must be supplemented so as to promote the conversion of hyperhomocysteine into S-adenosylmethionine or methionine by means of methylation, so that the homocysteine level can be reduced, and the damage to heart, brain, nerve and blood vessel can be eliminated.
The extract betaine of Geranium strictipes is an excellent methyl donor, which contains three active methyl groups in the molecule and is a direct and efficient methyl donor. It plays an important role in the process of homocysteine remethylation. It can promote the conversion of homocysteine into beneficial S-adenosylmethionine by combining with the nutritional ingredients such as carrier methyltetrahydrofolic acid, coenzyme cyanocobalamine, zinc, selenium and the like, thereby eliminating the damage of HCY to the organism. Methylation plays an important role in the nervous system and the cardiovascular and cerebrovascular systems, and can increase the synthesis capacity of neurotransmitter acetylcholine (brain hippocampal memory function marker). The elderly lack acetylcholine and memory and cognitive function will decline.
4. L-5-methyl-tetrahydrofolic Acid (methyl tetrahydrofolic Acid Lovo-Mefolic Acid): common folic acid is unstable in property, is easily damaged by gastric acid when being taken orally, and has absorption rate of only 50%. After being absorbed by small intestine, the active folic acid, namely L-5-methyl-tetrahydrofolic acid, can be directly used by human body without enzyme catalysis through a complex conversion process. The research of the invention finds that the L-5-methyl-tetrahydrofolic acid has better stability in a human body than natural folic acid, is not easy to damage, can be directly absorbed by the human body, and has the absorption rate which is 170 percent higher than that of the common folic acid, which is the reason for the composition to select the methyl tetrahydrofolic acid to replace the common folic acid.
The research of the invention finds that the HCY can be reduced by 17% by singly taking high-dose folic acid orally; the single oral administration of vitamin B12 can reduce HCY by 19%, and the combined oral administration of the two can reduce HCY by 57%, so that the effect of using common folic acid alone is not obvious, and active methyltetrahydrofolic acid is required to be combined with the heaven-grass extract (betaine) and cyanocobalamine to exert better effect of reducing HCY.
5. Ginkgo leaf extract: improving blood circulation and cerebral blood circulation disorder, cerebral ischemia, anoxia and glucose deficiency are important factors causing hypomnesis, mild cognitive impairment and vascular occlusive dementia (VD). The folium Ginkgo extract contains ginkgolide and multiple flavonol glycosides, and has multiple active ingredients beneficial for improving cardiovascular and cerebrovascular blood circulation and enhancing memory.
A. Oxidation resistance
Improving activity of superoxide dismutase (SOD), protecting blood vessel endothelial cells, softening blood vessel, removing plaque deposited on blood vessel wall, reducing blood vessel resistance, and increasing cerebral blood flow. In addition, the ginkgo biloba extract can also improve the blood supply of the peripheral nervous system, thereby improving cognitive, memory, voice, orientation and mental disorders caused by nerve cell degeneration and aging.
B. Reduce blood viscosity, enhance erythrocyte deformability, avoid tiny blood vessel blockage, and promote smooth blood flow.
C. Anticoagulant and antithrombotic effects. Platelet activating factor is an important factor in thrombosis and atherosclerosis. The ginkgolide has the function of specifically antagonizing platelet activating factor, and is an unavailable natural anticoagulant antithrombotic active ingredient.
The invention has the advantages of supplementing cholinergic neurotransmitter; antagonizing cholinesterase activity with a cholinesterase inhibitor; supplementing methyl donor, reducing high HCY level, protecting brain nerve cells, preventing vascular endothelial cells from being damaged, and relieving encephalatrophy; resisting damage of free radical oxidative stress to nerve cells and vascular endothelial cells; improving erythrocyte deformability and blood viscosity; platelet aggregation resistance, prevention of blood clots and thrombosis; improving the blood circulation of heart and brain; the compound multi-target intervention and comprehensive nutrition treatment measures achieve the aims of dredging cerebral blood flow, improving cerebral nerves, brain cells and cerebral vascular degeneration and senilism, improving memory function, improving learning ability and improving cognitive dysfunction.
The invention aims at the main factors influencing the decline of cognitive functions, including: cholinergic neurotransmitter deficiency, free radical oxidation damage, hyperhomocysteine damage; the invention implements multi-target coordinated nutritional intervention to improve cognitive function.
The coordination and coordination of the compositions:
A. supplementation of cholinergic neurotransmitter insufficiency:
the L-carnitine, the fructus alpiniae oxyphyllae extract and the semiaquilegia root extract coordinate to improve the content of the cholinergic neurotransmitter L-acetylcholine;
B. reduction of homocysteine:
the ginkgo biloba extract, the semiaquilegia extract, the L-5-methyl-tetrahydrofolic acid and the cyanocobalamine synergistically reduce the damage of homocysteine;
C. oxidation resistance and free radical toxicity removal:
the components are combined to resist oxidation and eliminate the toxicity of free radicals;
D. the ginkgo leaf extract, the semiaquilegia root extract, the cyanocobalamine and the L-5-methyl-tetrahydrofolic acid which improve the blood circulation synergistically reduce homocysteine, and simultaneously synergistically prevent coagulation and thrombosis, reduce blood viscosity and improve the strain capacity of red blood cells, and the factors coordinate to improve the brain blood circulation, thereby ensuring the supply of necessary nutrient components of brain nerve cells and the elimination of nerve excitotoxicity.
E. The combination of multiple target points exerts greater effect
MCI is formed by a combination of multiple deleterious factors, and therefore its strategy must also be multi-targeted for combination therapy and nutritional intervention.
Detailed Description
Example 1
A targeted health product for improving mild cognitive dysfunction is in the form of tablet, and comprises L-carnitine, fructus Alpinae Oxyphyllae extract, folium Ginkgo extract, herba Semiaquilegiae extract, cyanocobalamin, L-5-methyl-tetrahydrofolic acid, and adjuvants such as calcium hydrogen phosphate, hydroxymethyl propyl cellulose, silicon dioxide, magnesium stearate, and liquid paraffin. The weight percentage of each component is as follows:
the preparation method of the two raw materials of the targeted nutriment for improving the mild cognitive dysfunction and the tablets and capsules comprises the following steps:
1. preparing raw materials:
the preparation method of the fructus alpiniae oxyphyllae extract comprises the following steps: a method for extracting fructus Alpinae Oxyphyllae extract with surfactant and glycyrrhizin in cooperation with microwave is provided. Removing impurities and foreign matters from fructus Alpinae Oxyphyllae, pulverizing with a pulverizer, sieving with 80 mesh sieve to obtain fructus Alpinae Oxyphyllae powder, weighing 100 parts of fructus Alpinae Oxyphyllae powder, 0.4 part of surfactant glycyrrhizin, adding 500 parts of water, soaking at 60 deg.C for 1 hr, extracting with microwave oven for 25min with microwave power of 300w, separating the obtained mixture with a 4000r/min centrifuge to obtain centrifugate, repeating for 2 times, mixing the centrifugates for 3 times, and vacuum concentrating and drying to obtain fructus Alpinae Oxyphyllae extract.
The preparation method of the semiaquilegia root extract comprises the following steps: a method for extracting herba Geranii extract with surfactant and glycyrrhizin in cooperation with microwave is provided. Collecting the tender leaf of the new-born Tianjing grass, drying in the shade, crushing by a crusher, and sieving by a 20-mesh sieve to obtain the crude Tianjing grass powder. Taking 100 parts of semiaquilegia root coarse powder, 0.6 part of surfactant glycyrrhizin, adding 700 parts of water, soaking for 1 hour at a constant temperature of 60 ℃, moving to a microwave oven for auxiliary extraction for 20 minutes, performing microwave power of 200w, separating the obtained mixture by a centrifuge of 4000r/min to obtain centrifugate, repeating for 2 times, combining 3 centrifugates, and performing vacuum concentration and drying to obtain the semiaquilegia root extract.
The preparation method of the ginkgo leaf extract comprises the following steps: collecting folium Ginkgo, drying, pulverizing with a pulverizer, and sieving with 50 mesh sieve to obtain folium Ginkgo powder. Taking 100 parts of ginkgo leaf powder, adding 650 parts of water, and decocting to obtain the ginkgo leaf extract.
The fructus alpiniae oxyphyllae extract and the herba semiaquilegiae extract obtained by the preparation method are beneficial to exerting the drug effect and have better effect.
2. Preparation of tablets:
b, ingredient granulation a: weighing cyanocobalamine and L-5-methyl-tetrahydrofolic acid, uniformly mixing, adding equivalent calcium hydrogen phosphate, uniformly mixing by 4 times of equivalent increment, adding calcium hydrogen phosphate, uniformly mixing by two times of equivalent increment, mixing for 30 minutes, adding hydroxymethyl propyl cellulose, granulating by a 14-mesh stainless steel screen, drying at 60-80 ℃, grading by a 16-mesh stainless steel screen, and controlling the moisture of the granules to be 3.0-4.0%.
B, ingredient granulation: mixing fructus Alpinae Oxyphyllae extract, herba Veronicastri extract, and folium Ginkgo extract, dry mixing for 30 min, adding 80% ethanol, granulating with 14 mesh stainless steel sieve, drying at 60-80 deg.C, grading with 16 mesh stainless steel sieve, and controlling water content of the granule to 3.0-4.0%.
And (c) material preparation and granulation: the L-carnitine is taken and added with liquid paraffin to be mixed for 30 minutes, and then granulated through a 16-mesh stainless steel screen.
Tabletting: and (3) uniformly mixing the 3 granules, adding hydroxymethyl propyl cellulose, silicon dioxide and magnesium stearate, uniformly mixing for 20 minutes, and tabletting to obtain tablets with the weight of 0.6 g.
The composition has certain moisture absorption, and the relative humidity of a tabletting workshop is preferably controlled at 50%.
Coating: and (5) coating a compact film coat.
Example 2
A target health product for improving mild cognitive dysfunction is in the form of capsule, and comprises L-carnitine, fructus Alpinae Oxyphyllae extract, folium Ginkgo extract, herba Semiaquilegiae extract, cyanocobalamin, L-5-methyl-tetrahydrofolic acid, and adjuvants such as calcium hydrogen phosphate, hydroxymethyl propyl cellulose, silicon dioxide, and liquid paraffin. The weight percentage of each component is as follows:
granulating by grouping ingredients a: weighing cyanocobalamine and L-5-methyl-tetrahydrofolic acid, uniformly mixing, adding equivalent calcium hydrophosphate, uniformly mixing by 4 times of equivalent increment, adding calcium hydrophosphate, uniformly mixing by two times of equivalent increment, dry-mixing for 30 minutes, adding hydroxymethyl propyl cellulose, granulating by a 14-mesh stainless steel screen, drying at 60-80 ℃, granulating by a 16-mesh stainless steel screen, and controlling the moisture of the granules to be 3.0-4.0%.
And (b) granulating by grouping ingredients: weighing fructus Alpinae Oxyphyllae extract, herba Semiaquilegiae extract, and folium Ginkgo extract, dry mixing for 30 min, adding 80% ethanol, granulating with 14 mesh stainless steel sieve, drying at 60-80 deg.C, grading with 16 mesh stainless steel sieve, and controlling water content of the granule to 3.0-4.0%.
And (4) granulating by grouping ingredients: the L-carnitine is taken and added with liquid paraffin to be mixed for 30 minutes, and then granulated through a 16-mesh stainless steel screen.
Filling a capsule: mixing the above 3 kinds of granules, adding silicon dioxide, mixing for 20min, and making into capsule. The loading amount is 0.3 g each. The composition has certain moisture absorption, and the temperature of a capsule filling workshop is controlled to be 25 ℃ and the humidity is controlled to be about 50%.
Comparative example 1
A health product for improving mild cognitive dysfunction is in the form of tablet, and comprises L-carnitine, fructus Alpinae Oxyphyllae extract, folium Ginkgo extract, cyanocobalamine, folic acid, and adjuvants such as calcium hydrogen phosphate, hydroxymethyl propyl cellulose, silicon dioxide, magnesium stearate, and liquid paraffin. The weight percentage of each component is as follows:
comparative example 2
A health product for improving mild cognitive dysfunction is in the form of tablet, and comprises folium Ginkgo extract, herba Semiaquilegiae extract, cyanocobalamine, folic acid, and adjuvants such as calcium hydrogen phosphate, hydroxymethyl propyl cellulose, silicon dioxide, magnesium stearate, and liquid paraffin.
The weight percentage of each component is as follows:
the preparation method comprises the following steps:
preparing materials and granulating: weighing cyanocobalamine and folic acid, uniformly mixing, adding equivalent calcium hydrophosphate, uniformly mixing by 4 times of equivalent increment, adding a herba Geranii extract, adding calcium hydrophosphate, uniformly mixing by two times of equivalent increment, dry-mixing for 30 minutes, adding starch, granulating by a 14-mesh stainless steel screen, drying at 60-80 ℃, grading by a 16-mesh stainless steel screen, and controlling the water content of the granules to be 3.0-4.0%.
Preparing materials and granulating: mixing herba Sedi Aizoon extract and folium Ginkgo extract, dry mixing for 30 min, adding 80% ethanol, granulating with 14 mesh stainless steel sieve, drying at 60-80 deg.C, grading with 16 mesh stainless steel sieve, and controlling water content of the granule to 3.0-4.0%.
The other steps were as in example 1.
Comparative example 3
A health product for improving mild cognitive impairment is a tablet, and comprises the following components in percentage by weight:
the preparation is as in example 1. The difference is that the preparation method of the sharpleaf galangal fruit extract, the ginkgo leaf extract and the semiaquilegia root extract is that the extracts are obtained by decocting and concentrating the respective substances.
The patients diagnosed with mild cognitive dysfunction were scored using MMSE scoring, and the patient's condition before and after dosing was compared, with the specific results shown in table 3.
TABLE 3 comparison table of effective rates of different drugs
As can be seen from the data in table 3, the effective rate of the drug of example 1 is 86.67%, the effective rate of comparative example 1 is 41.67%, the effective rate of comparative example 2 is 57.14%, and the effective rate of comparative example 3 is 46.67%. The invention has obvious effect and can effectively improve the cure rate of mild cognitive dysfunction.
Claims (5)
1. A targeted composition for improving mild cognitive dysfunction is characterized by comprising, by weight, 20-30% of L-carnitine, 15-30% of fructus alpiniae oxyphyllae extract, 10-30% of ginkgo leaf extract, 10-30% of herba semiaquilegiae extract, 0.005-0.02% of cyanocobalamin, 0.01-0.03% of L-5-methyl-tetrahydrofolic acid and 10-30% of auxiliary materials;
the preparation method of the extractive of the semiaquilegia root comprises the steps of drying and crushing the tender leaf of the semiaquilegia root to obtain semiaquilegia root powder, mixing the semiaquilegia root powder, water and glycyrrhizin, wherein the weight ratio of the semiaquilegia root powder, the water and the glycyrrhizin is 100: 500: 700: 0.2-1; soaking at 50-70 deg.C, microwave extracting, separating, concentrating, and drying to obtain herba Sedi Aizoon extract;
the preparation method of the fructus alpiniae oxyphyllae extract comprises the steps of mixing fructus alpiniae oxyphyllae powder, water and glycyrrhizin, wherein the weight ratio of the fructus alpiniae oxyphyllae powder to the water to the glycyrrhizin is 100: 500-; soaking at 50-70 deg.C, microwave extracting, separating, concentrating, and drying to obtain fructus Alpinae Oxyphyllae extract;
the preparation method of the ginkgo leaf extract comprises the steps of mixing ginkgo leaf powder and water, wherein the weight ratio of the ginkgo leaf powder to the water is 1:5-20, and decocting to obtain the ginkgo leaf extract.
2. The targeting composition as set forth in claim 1, which comprises, by weight, 25-30% of L-carnitine, 20-25% of Alpinia oxyphylla extract, 10-20% of Ginkgo biloba extract, 10-20% of Geranium japonicum extract, 0.005-0.02% of cyanocobalamin, 0.01-0.03% of L-5-methyl-tetrahydrofolic acid, and 15-25% of an adjuvant.
3. The targeting composition of claim 1 or 2 wherein said l-carnitine comprises l-carnitine tartrate, l-carnitine fumarate or acetyl l-carnitine salt.
4. The targeting composition according to claim 1 or 2 wherein said excipients are one or more of dibasic calcium phosphate, hydroxymethyl propyl cellulose, liquid paraffin, silicon dioxide, magnesium stearate.
5. A method for preparing a targeted composition according to any one of claims 1 to 4, comprising the steps of mixing L-carnitine, Alpinia oxyphylla extract, Ginkgo biloba extract, Geranium strictipes extract, cyanocobalamin, L-5-methyl-tetrahydrofolic acid and adjuvants, granulating, and preparing into tablets or capsules.
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| KR20230011999A (en) * | 2020-05-15 | 2023-01-25 | 알파시그마 에스.피.에이. | Composition comprising methylfolate |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1985993A (en) * | 2006-12-29 | 2007-06-27 | 淮北市辉克药业有限公司 | Compound preparation for enhancing memory |
| CN102516247A (en) * | 2010-12-15 | 2012-06-27 | 连云港金康医药科技有限公司 | A-type calcium L-5-methyltetrahydrofolate polymorphism and preparation method thereof |
| CN103118743A (en) * | 2010-07-01 | 2013-05-22 | Isis创新有限公司 | Treatment of cognitive disorders |
| EP2303019A4 (en) * | 2008-06-25 | 2013-07-17 | Bermans S Iskandar | (6s)-5-methyltetrahydrofolic acid for therapy of tissue injury |
-
2018
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1985993A (en) * | 2006-12-29 | 2007-06-27 | 淮北市辉克药业有限公司 | Compound preparation for enhancing memory |
| EP2303019A4 (en) * | 2008-06-25 | 2013-07-17 | Bermans S Iskandar | (6s)-5-methyltetrahydrofolic acid for therapy of tissue injury |
| CN103118743A (en) * | 2010-07-01 | 2013-05-22 | Isis创新有限公司 | Treatment of cognitive disorders |
| CN102516247A (en) * | 2010-12-15 | 2012-06-27 | 连云港金康医药科技有限公司 | A-type calcium L-5-methyltetrahydrofolate polymorphism and preparation method thereof |
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