CN109793774A - A kind of substance application and preparation method for alzheimer's disease prevention and treatment - Google Patents
A kind of substance application and preparation method for alzheimer's disease prevention and treatment Download PDFInfo
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- CN109793774A CN109793774A CN201711136367.6A CN201711136367A CN109793774A CN 109793774 A CN109793774 A CN 109793774A CN 201711136367 A CN201711136367 A CN 201711136367A CN 109793774 A CN109793774 A CN 109793774A
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Abstract
The present invention discloses product of distillation and its application of the fatty contents of seeds of rubber tree.The substance is the product of distillation of the fatty contents of the seed of rubber tree, can be applied to drug, health food, in food, the prevention and treatment for Alzheimer's.The preparation method of the substance is under vacuum conditions, to raw material heat temperature raising, and to be passed through water vapour to extract from the liposoluble substance of seeds of rubber tree as raw material and distilled.The gaseous molecular that water vapour carries out is condensed, the grease floated on condensed water is the product of distillation of the fatty contents of seeds of rubber tree.Alzheimer's pass through daily to be taken or the edible drug, health food, food for being added to the substance can be obtained good prevention and treatment effect.
Description
Technical field
The invention belongs to biomedicine fields, and specifically the present invention relates to one kind carries out for Alzheimer's
The product of distillation of the fatty contents of the substance of prevention and treatment -- seeds of rubber tree and its application.
Background technique
In history, president Rigen of resignation, Britain former prime minister Mrs Thatcher, " century-old lonely " author's marc this and
The father Gao Kun that Nobel Prize in physics in 2009 obtains main fiber has suffered from alzheimer's disease in the evening of life.
The sea A Erzi nurse is sick (AD), is commonly called as senile dementia, is a kind of neurodegenerative disease, with progressive failure of memory and
It obtains sex knowledge to lose, until daily life active ability completely loses and is characterized, brings heavy burden to society and family, at
For serious society and health care problem.Alzheimer's disease is threatened old after cardiovascular disease, cerebrovascular disease and tumour
The important diseases reason of year people's health.
The cause of disease and its pathogenesis of Alzheimer's disease are still not clear, at present it is believed that Alzheimer's disease and something lost
The factors such as biography, aging, immunologic dysfunction, sex hormone level, environment are related.Propose Different types of etiopathogenises hypothesis, including gallbladder
Alkali energy hypothesis, A β abnormal deposition hypothesis, Tau albumen hypothesis, radical damage hypothesis, gene mutation hypothesis etc., wherein choline
It can hypothesis, A β abnormal deposition hypothesis, Tau albumen hypothesis influence power maximum.
According to the statistics made by the departments concerned, by 2015, global Alzheimer patient was 46,800,000 people, it is contemplated that the year two thousand thirty will
Up to 74,700,000 people, the year two thousand fifty will more break through 131,500,000 people.
It is shown according to epidemiological survey data, by 2013, there are about 62% dull-witted cases to concentrate in development in the whole world
National (low income and middle income country) will have 71% patient to concentrate on developing country by the year two thousand fifty, wherein aged
Changing progress is most rapidly China, India and South Asia, West Pacific region.
Only between 1998 to 2015 years, major pharmacy giant is proposed the drug of 123 kinds for the treatment of alzheimer's diseases altogether,
The listing for only adding a kind of combined treatment successively to obtain FDA there are three types of drug is ratified.However, without exception, this 123 kinds of drugs
Alzheimer's disease can be cured without one kind, or even disease process is delayed all not accomplish.Even obtaining controlling for FDA approval
Treatment scheme also only plays the role of alleviating partial symptoms.
Alzheimer's common drug mainly include the following types:
1, improve choline neurotransmission drug, such as acetylcholinesterase (AchE) inhibitor, including Tacrine, Aricept, Ai Si
Energy, galanthamine etc..Tacrine is since it has serious hepatotoxicity wind agitation, and dosage is big, half-life short, is washed in a pan by China's clinic
It eliminates.Aricept, Exelon and galanthamine have the intestines and stomaches adverse reaction such as Nausea and vomiting, can disappear after drug withdrawal.Australia
Adverse drug reaction Advisory Board (ADRAC) is after receiving 68 parts of adverse drug reaction reports, and warning doctors are it should be noted that control
Treat the cholinesterase inhibitor proarrhythmia of Alzheimer's disease, the especially potentiality of bradycardia.
2, improve brain blood circulation and brain cell metabolism drug, as piracetam, Duxil, hydergene, pentoxifylline,
Brain is logical etc..Piracetam and Duxil have the adverse reaction of digestive system and central nervous system, as Nausea and vomiting, abdominal pain, easily
Excitement, headache and sleep disturbance etc., symptom weight is directly related with medication metering, and symptom disappears after drug withdrawal.
3, calcium antagonist: such drug is easy to through blood-brain barrier, selective expansion of cerebral vascular, reduces because of flow of calcium ions
Caused by neural cell injury or death, so as to improve memory and cognitive function.The most commonly used is Nimodipines, do not have gastrointestinal tract
Adverse reaction, but there are the side effects such as thrombopenia, tachycardia, low blood pressure.
4, hormone medicine can improve secondary AD symptom, but be easy to induce breast cancer, carcinoma of endometrium, coronary heart disease, soldier
In, phlebothrombosis etc..
5, nonsteroidal anti-inflammatory drug, such as brufen, Diclofenac, naproxen are likely to become treatment senile dementia
Active drug.Main adverse reaction in addition in terms of gastrointestinal tract and kidney, still have central nervous system, hematological system, skin and
The side effects such as liver, and the degree of these side effects and probability of happening are related to medication metering.
6, free radical scavenger and antioxidant, such as vitamin E, epiphysin, curcumin, vitamin C.Vitamin E and
The intake of curcumin long-term, high-dose can increase hemorrhagic apoplexy and cause danger, and curcumin also results in liver and gall-bladder poisoning, add
Diabetes are had serious side effects, easily cause complication by weight gall stone.Epiphysin has daytime drowsiness, headache, dizziness etc. are secondary to make
With high dose will affect ovulation, increase pregnancy difficulty.Vitamin C long-term, high-dose, which is taken, can cause gastrointestinal reaction, and stomach is caused to be burst
The pain increased or even bleeding for ulcer, also has damage to urinary system republicanism hematological system.
7, agonists of muscarinic receptors: high dose takes muscarine M1 receptor stimulating agent xanomeline, can obviously improve old
The cognitive function and action behavior ability of dementia patient.But due to serious side effects of the medicine in terms of stomach and intestine and angiocarpy,
Many patients are unable to continual cure.
Alzheimer's disease is considered as a kind of neurodegenerative disease that can not be cured at present, hundreds of in global implication
The health of ten thousand people, the drug of Current therapeutic Alzheimer often cause apparent body side effect.In face of Alzheimer
The huge ever-increasing patient populations of morbidity cardinal sum of disease are badly in need of developing more effective, less side effect or medicine without side-effects
Object is ailing to mitigate patient, while reducing because of the other physical impairments of drug side-effect bring.
Summary of the invention
The purpose of the present invention is to provide a kind of substance -- rubbers that prevention and treatment is carried out for Alzheimer's
The product of distillation of the fatty contents of gum seed and application.The substance is that the distillation of the fatty contents of the seed of rubber tree produces
Object can be applied to drug, health food, in food, the prevention and treatment for Alzheimer's.Alzheimer
Disease patient passes through daily to take or the edible drug, health food, food for being added to the substance can be obtained good prevention
With therapeutic effect.
In order to realize above-mentioned purpose of the invention, the present invention provides the following technical solutions:
The product of distillation of the fatty contents of seeds of rubber tree, the product of distillation of the fatty contents of the seeds of rubber tree by
Following methods are prepared:
Using virgin rubber tree species as raw material, after drying shelling, kernel is prepared, kernel passes through mechanical presses method, extraction
The lipoclastic of seeds of rubber tree is made in one or more of method, supercritical extraction.
Using the lipoclastic of seeds of rubber tree as raw material, under vacuum conditions, the absolute pressure range of vacuum degree is 0.01-
400Pa；Stop heating when heating to 250-260 DEG C to raw material, the temperature is maintained to terminate up to distillation, meanwhile, in raw material
Start to be passed through water vapour when being warming up to 160 DEG C and be distilled, the gaseous molecular that water vapour carries out is condensed, is floated on cold
Grease on condensate is the product of distillation of the fatty contents of seeds of rubber tree.
The present invention also provides the product of distillation of the seeds of rubber tree fatty contents containing therapeutically effective amount and pharmaceutically
The pharmaceutical composition of acceptable carrier.
And health food, it is made of the product of distillation and health food common carrier of seeds of rubber tree fatty contents.
With food is made of the product of distillation and food common carrier of seeds of rubber tree fatty contents.
Invention also provides the product of distillation of the fatty contents of seeds of rubber tree to treat Alzheimer in preparation
Application in the drug of disease.
Application as mentioned, wherein the product of distillation of the fatty contents of seeds of rubber tree is drug sole active agent.
Present invention further provides the product of distillation of the fatty contents of seeds of rubber tree in the sea preparation treatment A Erzi
Application in the health food of silent disease.
Application as mentioned, wherein the product of distillation of the fatty contents of seeds of rubber tree is the sole active of health food
Ingredient.
The present invention still further provides the product of distillation of the fatty contents of seeds of rubber tree in the sea preparation treatment A Erzi
Application in the food of silent disease.
As mentioned application, wherein the product of distillation of the fatty contents of seeds of rubber tree be food sole active at
Point.
According to the experimental data of alzheimer's disease animal model, and other experimental datas, with it is existing for Ah
The drug that the silent disease patient in Wurz sea carries out prevention and treatment is compared, the present invention has the advantage that
1, a kind of completely new substance is provided for the prevention and treatment of alzheimer's disease；
2, without side-effects, it can be used for a long time for Alzheimer's；
3, improve memory, enhancing distinguishes and judgement；
4, alleviate disease process, effectively the symptoms such as mitigation aphasia, appraxia and agnosia.
Specific embodiment
Embodiment 1
Using 100kg virgin rubber tree species as raw material, after drying shelling, kernel 40kg is prepared.Kernel material arrives 80- in heat
100 DEG C, then by static extruding, pressure 50MPa, squeezing out 12kg liquid is substance rubber tree species of the invention
Sub- fatty contents.
The liposoluble substance of seeds of rubber tree is extracted from as raw material using 10kg, under vacuum conditions, to raw material heat temperature raising,
And it is passed through water vapour and is distilled.The gaseous molecular that water vapour carries out is condensed, the oily on condensed water is floated on
Object is the product of distillation of the fatty contents of seeds of rubber tree.Distillation condition are as follows: the absolute pressure of vacuum degree is 0.01Pa；It is right
Raw material starts to be passed through water vapour when being heated to 160 DEG C, and heat is warming up to 250 DEG C and stops heating, maintains the temperature until steaming
End is evaporated, the product of distillation of the fatty contents of 0.9kg seeds of rubber tree is finally obtained.
The senile plaque of A β peptide formation is the main reason for causing a series of Alzheimer symptoms (AD symptom), in mouse pair
Parahippocampal gyrus injection A β tire in side can prepare the animal model of Alzheimer symptom (AD symptom).
Mice water maze experiment is a kind of forced experimental animal (rat, mouse) swimming, and study is found to hide and be put down in water
A kind of experiment of platform, test program are divided into orientation navigation experiment and space exploration experiment, are mainly used for test experiments animal to sky
Between position sense and sense of direction (space orientation) ability of learning and memory.For in orientation navigation experiment, mouse escapes in labyrinth
It is shorter to keep away incubation period, then illustrates that its ability of learning and memory is strong；In space exploration experiment, mouse is got in the original platform quadrant residence time
Length, more its ability of learning and memory of explanation of traversing times are stronger.Alzheimer symptom (AD disease processed for different pharmaceutical
Shape) mouse, detects its escape latent time in water maze, spanning platform number, it can be estimated that these drugs of drug therapy
For treating the effect of Alzheimer's disease.
The healthy Kunming mouse 75 of SPF grades of test selection, half male and half female, weight is 20 ± 2g, by Chinese Academy of Sciences elder brother
Bright Institute of Botany provides, production licence number: the Yunnan SCXK() K2016-0001.5 groups are randomly divided into, sham-operation group, model group
(A β group) and substance high dose group of the present invention (stomach-filling amount is 3g/kg, is equivalent to 30 times of human body high dose 100mg/kg), middle dose
The distillation of amount group (stomach-filling amount is 1.5g/kg, is equivalent to 30 times of human body middle dosage 50mg/kg), olive fruit fatty contents produces
Object group (abbreviation olive group, stomach-filling amount are 1.5g/kg).
After 5% chloraldurate 0.7ml/100g anesthesia is injected intraperitoneally, mouse is fixed on both arms stereotaxic apparatus, office
Size top unhairing, disinfection, median sagittal position notch by periosteum separation, strip, determine forward and backward fontanel, and be allowed in same level
On face, taking bregma is 0 point, selects to be returned by bilateral hippocampus as injection target area after incision (referring to George Paxinos and Keith
The mouse brain map of B.J.Franklin, using Bregma point as origin, 3.0mm after bregma, middle line or so is other to open 2.2mm, firmly
2.8mm under meninx).It is drilled after positioning with cranium, respectively by 10uLA β (A β25-35, lot number A2005, purchased from Sigma Co., USA) and slow
By slow injection bilateral hippocampus, injection time 10min, let the acupuncture needle remain at a certain point after every side injection 5min are sealed with dental base acrylic resin powder and 502 glue mixtures
Drilling is closed to sew up the incision.Sham-operation group gives isometric artificial cerebrospinal fluid.Operation is put into cage after terminating mouse revival, and operation is complete
Claim to keep sterile, to avoid mouse infection, appropriate penicillin is injected intraperitoneally.Restore 3d after mouse modeling and gives drug progress in fact
It tests.
Morris water maze test carries out water maze test after 10d is administered, and Morris water maze diameter is 100cm, height
The high 40cm of 60cm, platform, depth of water 42cm.Using 4 points of pool edge equal distribution as place of entry, round pool is divided into
4 quadrants, platform is located in a certain quadrant, at the 2cm of underwater.Prepared Chinese ink is added in water, maintains water temperature at 25 ± 1 DEG C, water fan
Visual cues are relatively fixed outside palace.
Test includes: 1) orientation navigation experiment: experiment is carried out in daily same time period, for three days on end, 1 times/day, and respectively
Mouse head is entered into water towards pool wall from 4 1/2 radians of quadrant edge, allow mouse found with 60s hide it is underwater escape it is flat
Platform allows to stop 10s on platform after finding platform, if can not find platform at the appointed time, it is flat that experimenter helps it to find
Platform simultaneously allows to stop 10s on platform, and entering water to the time for finding platform is escape latency.4th day, successively from second and third,
Four-quadrant place of entry by mouse towards pool wall into the water, record escape latency respectively.2) space exploration is tested: the 5th day (fixed
Position navigation experiment is one day after), platform is removed, allows mouse free swimming, in limited time 60s.Whole experiment process is carried out with camera system
Real time monitoring, and record the number of mouse spanning platform position in 60s.
The activity for closing (NOS) to AD model mice A amyloid beta precipitating and hippocampal tissue nitric oxide carries out detection point
Analysis, assesses anti-AD effect.The result shows that there is a large amount of A amyloid beta precipitating, and water fan in AD model mice hippocampus
Longer escape latency, ability of learning and memory decline are shown in the test of palace, it was demonstrated that the success of AD model construction.Carrying out 10d
Stomach-filling processing after, substance middle dose group hippocampus of mice area of the present invention A amyloid beta precipitating substantially reduce, substance of the present invention
The reduction that high dose group precipitates A amyloid beta is the most obvious.
1 water maze orientation navigation of table and space exploration experimental result (n=10,)
| Group | 1st day | 2nd day | 3rd day | 4th day | Spanning platform (secondary) |
| Sham-operation group | 23.92±11.02 | 19.46±4.23 | 14.78±6.45 | 9.46±3.48 | 2.75±2.11 |
| A β group | 36.24±10.57a | 30.14±6.78a | 23.36±8.56a | 17.48±7.56a | 1.03±0.97a |
| Substance middle dose group of the present invention | 28.65±8.32 | 21.32±6.86b | 16.24±7.56b | 10.78±3.21b | 3.03±2.27b |
| Substance high dose group of the present invention | 26.25±7.87b | 20.36±5.98b | 15.21±7.33b | 10.19±3.14b | 3.12±2.02b |
| Olive group | 35.13±10.86 | 29.67±6.85 | 23.37±8.35 | 16.64±7.63 | 1.18±1.04 |
Note: compared with sham-operation group, a:p < 0.05, compared with A β group, b:p < 0.05
With the increase of experiment number of days, the escape latency of all experimental mices is all gradually shortened, and illustrates that each group mouse has
Certain ability of learning and memory；Compared with sham-operation group, A β group mouse escape latency significantly extends (p < 0.05), with A β group phase
Than, the escape latency of olive group at the 1-4 days without significant difference, and the middle dose group and high dose group of substance of the present invention exist
There were significant differences (p < 0.05) with A β group within the 1-4 days.
Space exploration experiment in, the number that A β group mouse passes through original platform position be considerably less than sham-operation group (p <
0.05)；Compared with A β group, traversing times significantly increase (p < 0.05) for substance middle dosage of the present invention, high dose group, and olive group with
A β group is not significant compared to difference.
This example demonstrates that substance middle dosage of the present invention and high dose group learn Alzheimer symptom (AD symptom) mouse
Habit memory capability improves significantly and humidification, and fish oil effect is unobvious, this illustrates that substance of the invention has treatment
The effect of alzheimer's disease.
Embodiment 2
Using 100kg virgin rubber tree species as raw material, after drying shelling, kernel 40kg is prepared.Kernel material arrives 80- in heat
100 DEG C, then by static extruding, pressure 50MPa, squeezing out 12kg liquid is substance rubber tree species of the invention
Sub- fatty contents.
The liposoluble substance of seeds of rubber tree is extracted from as raw material using 10kg, under vacuum conditions, to raw material heat temperature raising,
And it is passed through water vapour and is distilled.The gaseous molecular that water vapour carries out is condensed, the oily on condensed water is floated on
Object is the product of distillation of the fatty contents of seeds of rubber tree.Distillation condition are as follows: the absolute pressure of vacuum degree is 0.01Pa；It is right
Raw material starts to be passed through water vapour when being heated to 160 DEG C, and heat is warming up to 250 DEG C and stops heating, maintains the temperature until steaming
End is evaporated, the product of distillation of the fatty contents of 0.9kg seeds of rubber tree is finally obtained.
The senile plaque of A β peptide formation is the main reason for causing a series of Alzheimer symptoms (AD symptom), in mouse pair
Parahippocampal gyrus injection A β tire in side can prepare the animal model of Alzheimer symptom (AD symptom).
Elevated plus-maze (High plus maze) be using animal to strange environment probe into characteristic and to uphanging it is spacious
The frightened of open arms forms contradiction behavior to investigate the anxiety state of animal.Rodent can tend to due to thermophilic dark property
It is movable to close in arm, but out of curiosity with inquiry again can in open arms it is movable, when in face of novel stimulus, animal generates simultaneously
The impulsion and frightened, this conflict behavior that has resulted in probing into and avoid probed into, to generate anxious psychology.Relative to normal small
Mouse (including sham-operation mouse), number of Alzheimer symptom (AD symptom) model mice in the open arms of Elevated plus-maze
It all can be less with the time.With different drug-treated Alzheimer symptom (AD symptom) model mices, detect they
Number and time in the open arms of Elevated plus-maze, it can be estimated that effect of these drugs on treatment alzheimer's disease.
The healthy Kunming mouse 75 of SPF grades of test selection, half male and half female, weight is 20 ± 2g, by Chinese Academy of Sciences elder brother
Bright Institute of Botany provides, production licence number: the Yunnan SCXK() K2016-0001.5 groups are randomly divided into, sham-operation group, model group
(A β group) and substance high dose group of the present invention (stomach-filling amount is 3g/kg, is equivalent to 30 times of human body high dose 100mg/kg), middle dose
The distillation of amount group (stomach-filling amount is 1.5g/kg, is equivalent to 30 times of human body middle dosage 50mg/kg), olive fruit fatty contents produces
Object group (abbreviation olive group, stomach-filling amount are 1.5g/kg).
After 5% chloraldurate 0.7ml/100g anesthesia is injected intraperitoneally, mouse is fixed on both arms stereotaxic apparatus, office
Size top unhairing, disinfection, median sagittal position notch by periosteum separation, strip, determine forward and backward fontanel, and be allowed in same level
On face, taking bregma is 0 point, selects to be returned by bilateral hippocampus as injection target area after incision (referring to George Paxinos and Keith
The mouse brain map of B.J.Franklin, using Bregma point as origin, 3.0mm after bregma, middle line or so is other to open 2.2mm, firmly
2.8mm under meninx).It is drilled after positioning with cranium, 10uLA β is slowly injected by bilateral hippocampus respectively, injection time 10min, every side
Let the acupuncture needle remain at a certain point after injection 5min is sewed up the incision with dental base acrylic resin powder and the closing drilling of 502 glue mixtures.Sham-operation group gives isometric people
Work cerebrospinal fluid.Operation is put into cage after terminating mouse revival, and operation full name keeps sterile, to avoid mouse infection, intraperitoneal injection
Appropriate penicillin.Recovery 3d gives drug and is tested after mouse modeling.
Experimental provision by having a size of 50cm × 5cm(long × wide) two open arms and two close arm intersection and form, wherein
Closure arm is closed by the opaque wall of high 30cm, and middle section size is 5cm × 5cm, is closed without wall.Whole device from
The height on ground is 45cm.After experiment starts, mouse is put into labyrinth towards open arms, it is allowed freely to explore 5min.Experiment
Observation index: open arms enter number, open arms residence time, closure arm enter number, closure arm residence time.Into opening
The anxiety of arm number and residence time and rat is negatively correlated, and fewer into open arms number, the residence time is shorter, explanation
The anxiety of mouse is more serious.
2 elevated plus-maze test result of table compare (n=10,)
| Group | Into open arms number | The percentage of total degree is accounted for into open arms number | The open arms residence time | The percentage of total residence time is accounted in the open arms residence time |
| Sham-operation group | 15.9±3.1 | 42.1±4.8 | 72.8±8.14 | 23.5±6.1 |
| A β group | 10.6±2.1a | 24.6±3.4a | 40.8±6.04a | 12.8±2.8a |
| Substance middle dose group of the present invention | 16.1±2.5b | 41.3±4.7b | 68.9±6.0b | 22.8±5.3b |
| Substance high dose group of the present invention | 16.0±2.8b | 39.8±5.2b | 70.4±5.7b | 21.6±5.0b |
| Olive group | 10.9±2.2 | 25.2±3.5 | 43.6±6.2 | 12.3±2.8 |
Note: compared with sham-operation group, a:p < 0.05, compared with A β group, b:p < 0.05
As shown in table 2, compared with sham-operation group, A β group mouse enters open arms number, open arms residence time, into open arms
Number account for total degree percentage, the percentage that the open arms residence time accounts for total residence time reduce and significant difference (P <
0.05).Compared with A β group, olive group enters number, residence time etc. without significant difference (P > 0.05) in open arms, and this hair
Bright substance middle dose group, high dose group mouse are entering open arms number, open arms residence time, total into open arms number Zhan
The percentage of number, the equal significant difference of percentage (P < 0.05) for accounting for total residence time in the open arms residence time, object of the present invention
Matter middle dose group, high dose group mouse are significant (P < 0.05) in the percentage difference for accounting for total degree into open arms number.
This illustrates that substance of the invention has the function for the treatment of alzheimer's disease.
Embodiment 3
Using 100kg virgin rubber tree species as raw material, after drying shelling, kernel 40kg is prepared.Kernel material arrives 80- in heat
100 DEG C, then by static extruding, pressure 50MPa, squeezing out 12kg liquid is substance rubber tree species of the invention
Sub- fatty contents.
The liposoluble substance of seeds of rubber tree is extracted from as raw material using 10kg, under vacuum conditions, to raw material heat temperature raising,
And it is passed through water vapour and is distilled.The gaseous molecular that water vapour carries out is condensed, the oily on condensed water is floated on
Object is the product of distillation of the fatty contents of seeds of rubber tree.Distillation condition are as follows: the absolute pressure of vacuum degree is 0.01Pa；It is right
Raw material starts to be passed through water vapour when being heated to 160 DEG C, and heat is warming up to 250 DEG C and stops heating, maintains the temperature until steaming
End is evaporated, the product of distillation of the fatty contents of 0.9kg seeds of rubber tree is finally obtained.
A pair of of identical twin's Alzheimer's, female, the age 67 years old, two people almost fell ill simultaneously, using simple
Mental status examination scale, daily life self-care scale inspection, two people's severity extents are identical.Two people use identical after morbidity
The basic pharmaceutical of kind and dosage starts to treat.Basic pharmaceutical is Nimodipine.
The daystart that first (elder sister) is treated from basic pharmaceutical is additionally taken disclosed by the invention for Alzheimer
Drug made of the substance that disease patient is treated, dose are that 1 gram/day (is suffered from substance of the present invention for alzheimer's disease
What person was treated uses meter).After 4 months, the dosage of the basic pharmaceutical (Nimodipine) of first is kept to original half, according to letter
Easy mental status examination scale, daily life self-care scale inspection, the state of an illness maintain to stablize.According still further to the basic pharmaceutical (Buddhist nun halved
Not Horizon) plus basic pharmaceutical (Ni Modi is deactivated (behind 1 year of morbidity treatment) after Substance treatment 8 months of 1 gram/Japanese invention
It is flat), drug made of the substance disclosed by the invention treated for Alzheimer's is only taken, dose is still
For 1 gram/day (in terms of the substance treated for Alzheimer's), patient is according to mini-mentalstate examination amount
Table, daily life self-care scale inspection, the state of an illness remain always stable, not further development and deterioration.
Second (younger sister) is treated with basic pharmaceutical always, other than normal diet, does not take any substance additionally,
But according to mini-mentalstate examination scale, daily life self-care scale inspection, the state of an illness is compared with first and is being sent out forward always
Exhibition, symptom are increasingly serious.
Embodiment 4
Using 100kg virgin rubber tree species as raw material, after drying shelling, kernel 40kg is prepared.Kernel material arrives 80- in heat
100 DEG C, then pass through dynamic screw extrusion, the screw extrusion time is 45 seconds or so, and squeezing out 15kg liquid is this hair
Bright substance seeds of rubber tree fatty contents.
The liposoluble substance of seeds of rubber tree is extracted from as raw material using 10kg, under vacuum conditions, to raw material heat temperature raising,
And it is passed through water vapour and is distilled.The gaseous molecular that water vapour carries out is condensed, the oily on condensed water is floated on
Object is the product of distillation of the fatty contents of seeds of rubber tree.Distillation condition are as follows: the absolute pressure of vacuum degree is 0.3Pa；It is right
Raw material starts to be passed through water vapour when being heated to 160 DEG C, and heat is warming up to 253 DEG C and stops heating, maintains the temperature until steaming
End is evaporated, the product of distillation of the fatty contents of 0.9kg seeds of rubber tree is finally obtained.
A pair of of identical twin's Alzheimer's, female, the age 70 years old, two people almost fell ill simultaneously, using simple
Mental status examination scale, daily life self-care scale inspection, two people's severity extents are identical.Two people use identical after morbidity
The memantine (1-amino-3,5-dimethylglycine amine hydrochlorate) of dosage is that basic drug is treated.
The daystart that first (elder sister) is treated from basic pharmaceutical is additionally taken disclosed by the invention for Alzheimer
Disease patient prevent and the substance treated made of health food, dose is 2 grams/day (to suffer from for alzheimer's disease
The substance meter that person prevents and treats).After 4 months, the dosage of the basic pharmaceutical (memantine) of first is kept to original one
Half, according to mini-mentalstate examination scale, daily life self-care scale inspection, the state of an illness maintains to stablize.According still further to the base halved
Basic medicine is deactivated (behind 1 year of morbidity treatment) behind Substance treatment 8 months of plinth drug (memantine) plus 2 grams/Japanese invention
Object (memantine) is only taken the substance disclosed by the invention for being prevented and being treated for Alzheimer's and is made
Health food, dose remains as the 2 grams/day (object for being prevented and being treated for Alzheimer's with the present invention
Matter meter), the state of an illness remains always stable, does not deteriorate further.
The daystart that second (younger sister) is treated from basic pharmaceutical, the additional edible fat-soluble object extracted from flex seed
Food made of the product of distillation of matter, amount are that 2 grams/day (are produced with the distillation of the liposoluble substance extracted from flex seed
Object meter).But according to mini-mentalstate examination scale, daily life self-care scale inspection as a result, second and first are compared, disease
Feelings are advancing always, and symptom is increasingly serious.
Embodiment 5
Using 100kg virgin rubber tree species as raw material, after drying shelling, kernel 40kg is prepared.Then kernel is subjected to extruding
After processing, it is put into the leaching container of sealing, the solvent of 2 times of weight is added.In 55 DEG C of (being lower than solvent boiling point) conditions and normal pressure
Under, material is stirred and is mixed with solvent, material is allowed to come into full contact with solvent.It staticly settles later, leaches solvent, then
120 DEG C (being higher than solvent boiling point temperature) under 100Pa vacuum condition, solvent is allowed to volatilize, staying 18kg liquid is
Substance seeds of rubber tree fatty contents of the invention.
The liposoluble substance of seeds of rubber tree is extracted from as raw material using 10kg, under vacuum conditions, to raw material heat temperature raising,
And it is passed through water vapour and is distilled.The gaseous molecular that water vapour carries out is condensed, the oily on condensed water is floated on
Object is the product of distillation of the fatty contents of seeds of rubber tree.Distillation condition are as follows: the absolute pressure of vacuum degree is 15Pa；To original
Material starts to be passed through water vapour when being heated to 160 DEG C, and heat is warming up to 257 DEG C and stops heating, maintains the temperature until distillation
Terminate, finally obtains the product of distillation of the fatty contents of 1.0kg seeds of rubber tree.
A pair of of identical twin's Alzheimer's, female, the age 72 years old, two people almost fell ill simultaneously, according to simple
Mental status examination scale, daily life self-care scale check that two people's severity extents are identical.Two people use identical after morbidity
The memantine (1-amino-3,5-dimethylglycine amine hydrochlorate) of dosage is that basic drug is treated.
The daystart that first (elder sister) is treated from basic pharmaceutical is additionally taken disclosed by the invention for Alzheimer
Disease patient prevent and the substance treated made of food, amount be 4 grams/day (with for Alzheimer's into
The substance meter of row prevention and treatment).After 4 months, the dosage of the basic pharmaceutical (memantine) of first is kept to original half, root
According to mini-mentalstate examination scale, daily life self-care scale inspection as a result, the state of an illness maintain stablize.According still further to the base halved
Basic medicine is deactivated (behind 1 year of morbidity treatment) behind Substance treatment 8 months of plinth drug (memantine) plus 4 grams/Japanese invention
Object (memantine) only eats the substance disclosed by the invention for being prevented and being treated for Alzheimer's and is made
Food, amount remain as 4 grams/day (by prevented for Alzheimer's and the substance treated in terms of), according to
Mini-mentalstate examination scale, daily life self-care scale inspection as a result, the state of an illness remains always stable, further development
And deterioration.
The daystart that second (younger sister) is treated from basic pharmaceutical, the additional edible fat-soluble object extracted from purple perilla seed
Food made of the product of distillation of matter, amount are that 4 grams/day (are produced with the distillation of the liposoluble substance extracted from purple perilla seed
Object meter), but compare the state of an illness with first and advancing always, symptom is got worse.
Embodiment 6
Using 100kg virgin rubber tree species as raw material, after drying shelling, kernel 40kg is prepared.Kernel is subjected to granulation processing
Later, it is put into the supercritical extract container of sealing pressure resistance, solvent is added, solvent quality is 2 times of quality of material.At 35 DEG C,
10MPa(is more than the critical-temperature and critical pressure of solvent) under conditions of, material is stirred and is mixed with solvent, allows material
It is come into full contact with solvent.It staticly settles later, leaches solvent, then under room temperature at 25 DEG C, reduce pressure to normal pressure
(0.1MPa), allows solvent to volatilize, and staying 18kg liquid is substance seeds of rubber tree fatty contents of the invention.
The liposoluble substance of seeds of rubber tree is extracted from as raw material using 10kg, under vacuum conditions, to raw material heat temperature raising,
And it is passed through water vapour and is distilled.The gaseous molecular that water vapour carries out is condensed, the oily on condensed water is floated on
Object is the product of distillation of the fatty contents of seeds of rubber tree.Distillation condition are as follows: the absolute pressure of vacuum degree is 400Pa；It is right
Raw material starts to be passed through water vapour when being heated to 160 DEG C, and heat is warming up to 260 DEG C and stops heating, maintains the temperature until steaming
End is evaporated, the product of distillation of the fatty contents of 1.1kg seeds of rubber tree is finally obtained.
A pair of of identical twin's Alzheimer's, male, the age 64 years old, two people almost fell ill simultaneously, according to simple
Mental status examination scale, daily life self-care scale check that two people's severity extents are identical.Two people use identical after morbidity
The memantine (1-amino-3,5-dimethylglycine amine hydrochlorate) of dosage is that basic drug is treated.
The daystart that first (elder brother) is treated from basic pharmaceutical is additionally taken disclosed by the invention for Alzheimer
Disease patient prevent and the substance treated made of food, amount be 6 grams/day (with for Alzheimer's into
The substance meter of row prevention and treatment).After 12 months, the dosage of the basic pharmaceutical (memantine) of first is kept to original half,
The state of an illness maintains to stablize.After Substance treatment 12 months of the basic pharmaceutical (memantine) plus 6 grams/Japanese invention that halve
(behind 2 years of morbidity treatment), deactivate basic pharmaceutical (memantine), only eat disclosed by the invention for alzheimer's disease
Patient prevent and the substance treated made of food, amount remains as 6 grams/day (for Alzheimer's
The substance meter for being prevented and being treated).During entire, examined according to mini-mentalstate examination scale, daily life self-care scale
It looks into, the state of an illness of first remains always stable, non-developing deeply, deterioration.
The daystart that second (younger brother) is treated from basic pharmaceutical, the additional edible fat-soluble object extracted from maize germ
Food made of the product of distillation of matter, amount are that 6 grams/day (are produced with the distillation of the liposoluble substance extracted from maize germ
Object meter), but according to mini-mentalstate examination scale, daily life self-care scale inspection as a result, compared with first, second
The state of an illness is advancing always, and symptom is increasingly serious.
Embodiment 7:
The product of distillation of seeds of rubber tree fatty contents of the invention is made by the method in embodiment 3-6, by the part with
Excipient, pelletizing press sheet is added in the ratio of excipient weight ratio 1:1 or 1:2.Tablet can be used as drug, health food or food
Product.
Embodiment 8:
The product of distillation of seeds of rubber tree fatty contents of the invention is made by the method in embodiment 3-6, by the part, packet
It is rolled in soft capsule material, routinely soft capsule is made in capsule preparations method.Soft capsule can be used as drug, health food or
Food.
Embodiment 9:
Added by the product of distillation that seeds of rubber tree fatty contents of the invention are made in the method in embodiment 3-6 with the part
Upper emulsifier, osmotic pressure regulator and water obtain emulsion for injection by high-pressure homogeneous emulsification.The emulsion for injection can be made
For drug.
Embodiment 10:
The product of distillation of seeds of rubber tree fatty contents of the invention is made by the method in embodiment 3-6, by the part, then
Tablet is made as follows:
Tablet: the product of distillation 100mg of seeds of rubber tree fatty contents
Appropriate starch
Appropriate corn pulp
Magnesium Stearate proper quantity
Preparation method: the product of distillation of seeds of rubber tree fatty contents is mixed with auxiliary agent, sieving, in suitable container
Even mixing, obtained granulating mixture tabletting.
Embodiment 11:
The product of distillation of seeds of rubber tree fatty contents of the invention is made by the method in embodiment 3-6, by the part, then
Soft capsule is made as follows:
Soft capsule: the product of distillation 500mg of seeds of rubber tree fatty contents
Appropriate gelatin
Appropriate glycerol
Appropriate amount of water
Preparation method: gelatin, glycerol, which are put into distilled water, to impregnate makes gelatin expansion, softening, is then uniformly mixed, obtains
Capsule material glue.Prepared capsule material glue is taken out, is coated in flat plate surface, keeps thickness uniform, then with 90 DEG C or so
Temperature heating, evaporates surface moisture, becomes the cushion compound for having certain toughness, having certain elasticity.Finally with pelleting mold or
Automatic rotation rolling capsule machine, the product of distillation (500mg) of seeds of rubber tree fatty contents is fitted into soft capsule skin, is produced soft
Capsule.
Embodiment 12:
The product of distillation of seeds of rubber tree fatty contents of the invention is made by the method in embodiment 3-6, by the part, then
Emulsion for injection is made as follows:
Emulsion for injection: the product of distillation 200g of seeds of rubber tree fatty contents
Appropriate lecithin
Appropriate glycerol
Appropriate sodium chloride
Appropriate amount of water
Preparation method: according to formula, by the product of distillation of seeds of rubber tree fatty contents, lecithin, glycerol mixing is added water to
1000mL, high-pressure homogeneous emulsification, 121 DEG C of sterilizings are down to room temperature to get emulsion for injection is arrived.
Embodiment 13:
Tablet: the product of distillation 10mg of seeds of rubber tree fatty contents of the invention being made by the method in embodiment 3-6, cream
Sugared 180mg, starch 55mg, magnesium stearate 5mg；
Preparation method: by be made by the method in embodiment 3-6 seeds of rubber tree fatty contents of the invention product of distillation,
Newborn sugar and starch mixing, is uniformly moistened with water, and the mixture after moistening is sieved and is dried, re-sieving, magnesium stearate is added, so
Afterwards by mixture tabletting, every slice weight 250mg, the product of distillation content of seeds of rubber tree fatty contents of the invention is 10mg.
Embodiment 14:
Capsule: the product of distillation of seeds of rubber tree fatty contents of the invention is made by the method in embodiment 3-6
2000g, gelatin 1000g, glycerol 500g, water 1000g；
Preparation method: by gelatin 1000g, glycerol 500g, being put into 1000g water to impregnate makes gelatin expansion, softening, and then stirring is mixed
It closes uniformly, obtains capsule material glue.Prepared capsule material glue is taken out, is coated in flat plate surface, keeps thickness uniform, then uses
90 DEG C or so of temperature heating, evaporates surface moisture, becomes the cushion compound for having certain toughness, having certain elasticity.Finally with pressure
Ball mold rotates rolling capsule machine automatically, and the product of distillation 500mg of seeds of rubber tree fatty contents is fitted into soft capsule skin,
Soft capsule is made.Every soft capsule weight 800mg, the product of distillation content of seeds of rubber tree fatty contents of the invention are
500mg。
Embodiment 15:
Emulsion for injection: the product of distillation of seeds of rubber tree fatty contents of the invention is made by the method in embodiment 3-6
200g, glycerol 25g, lecithin 12g, water 1000g, sodium chloride 1g,.
Preparation method: the steaming of seeds of rubber tree fatty contents of the invention is made by the method in embodiment 3-6 for accurate weighing
Evaporate product 200g, glycerol 25g, lecithin 12g, mix, add water to 1000mL, add sodium chloride, by osmotic pressure adjust to
350mosm/kg H2O.High-pressure homogeneous emulsification obtains emulsion, and 121 DEG C of sterilizings are down to room temperature, are aseptically filled to
It is encapsulated in the sterile glass vials of 250mL.Every bottle of emulsion for injection specification is 250mL, seeds of rubber tree fatty contents of the invention
Product of distillation content be 50g.
Embodiment 16:
Food: the product of distillation of seeds of rubber tree fatty contents of the invention is made by the method in embodiment 3-6, by the portion
Point, it is reconciled with oil with common edible, is directly becoming food (edible oil).
Preparation method: the distillation of seeds of rubber tree fatty contents of the invention is made by the method in embodiment 3-6 by 1kg
Product is added in 9kg soybean oil, obtains 10kg blending edible oil.By the filling vial at 500g of blending edible oil, this hair
The product of distillation content of bright seeds of rubber tree fatty contents is 50g.
Claims (10)
1. the product of distillation of the fatty contents of seeds of rubber tree, it is characterised in that the steaming of the fatty contents of the seeds of rubber tree
Product is evaporated to be prepared by the following method and obtain
Using virgin rubber tree species as raw material, after drying shelling, kernel is prepared, kernel passes through mechanical presses method, extraction
The lipoclastic of seeds of rubber tree is made in one or more of method, supercritical extraction, then with the lipoclastic of seeds of rubber tree
For raw material, under vacuum conditions, the absolute pressure range of vacuum degree is 0.01-400Pa；250-260 is heated to raw material
DEG C when stop heating, maintain the temperature until distillation terminates, meanwhile, start to be passed through when raw material is warming up to 160 DEG C water vapour into
Row distillation, condenses the gaseous molecular that water vapour carries out, and the grease floated on condensed water is seeds of rubber tree
Fatty contents product of distillation.
2. the product of distillation of the seeds of rubber tree fatty contents described in claim 1 containing therapeutically effective amount and pharmaceutically may be used
The pharmaceutical composition of the carrier of receiving.
3. health food is commonly used by the product of distillation and health food of seeds of rubber tree fatty contents described in claim 1
Carrier composition.
4. food is made of the product of distillation and food common carrier of seeds of rubber tree fatty contents described in claim 1.
5. the product of distillation of the fatty contents of seeds of rubber tree is in preparation prevention or the drug for the treatment of Alzheimer disease
In application.
6. application as claimed in claim 5, which is characterized in that the product of distillation of the fatty contents of seeds of rubber tree is medicine
Object sole active agent.
7. the product of distillation of the fatty contents of seeds of rubber tree is in preparation prevention or the health care for the treatment of Alzheimer disease
Application in food.
8. application as claimed in claim 7, which is characterized in that the product of distillation of the fatty contents of seeds of rubber tree is to protect
The sole active agent of health food.
9. the product of distillation of the fatty contents of seeds of rubber tree answering in the food of preparation rehabilitation Alzheimer disease
With.
10. application as claimed in claim 9, which is characterized in that the product of distillation of the fatty contents of seeds of rubber tree is
The sole active agent of food.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711136367.6A CN109793774A (en) | 2017-11-16 | 2017-11-16 | A kind of substance application and preparation method for alzheimer's disease prevention and treatment |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711136367.6A CN109793774A (en) | 2017-11-16 | 2017-11-16 | A kind of substance application and preparation method for alzheimer's disease prevention and treatment |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109793774A true CN109793774A (en) | 2019-05-24 |
Family
ID=66555346
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| CN201711136367.6A Pending CN109793774A (en) | 2017-11-16 | 2017-11-16 | A kind of substance application and preparation method for alzheimer's disease prevention and treatment |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1154217A (en) * | 1996-12-11 | 1997-07-16 | 曹敏 | Method for making edible health-care kernel and edible oil from seed of rubber tree |
| CN106109274A (en) * | 2016-07-14 | 2016-11-16 | 西双版纳华坤生物科技有限责任公司 | Application of seeds of rubber tree oil and preparation method thereof |
-
2017
- 2017-11-16 CN CN201711136367.6A patent/CN109793774A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1154217A (en) * | 1996-12-11 | 1997-07-16 | 曹敏 | Method for making edible health-care kernel and edible oil from seed of rubber tree |
| CN106109274A (en) * | 2016-07-14 | 2016-11-16 | 西双版纳华坤生物科技有限责任公司 | Application of seeds of rubber tree oil and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| 王慧敏: "橡胶籽油的提取、精炼及其氧化稳定性研究", 《中国优秀硕士学位论文全文数据库（电子期刊）工程科技Ι辑》 * |
| 陈建白: "橡胶种子油与ω-3脂肪酸", 《云南热作科技》 * |
| 高慧: "长期摄入α-亚麻酸对自然衰老大鼠学习记忆能力和阿尔茨海默病样改变的保护作用及机制", 《中国博士学位论文全文数据库（电子期刊）医药卫生科技辑》 * |
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