CN106344609A

CN106344609A - Application of ozonized oil in preventing and controlling nervous system diseases

Info

Publication number: CN106344609A
Application number: CN201610967762.8A
Authority: CN
Inventors: 李新平; 侯建生
Original assignee: Individual
Current assignee: Individual
Priority date: 2016-11-01
Filing date: 2016-11-01
Publication date: 2017-01-25

Abstract

The invention relates to ozonized oil used for preventing and treating nervous system diseases and a drug combined with the medicine for treating the nervous system diseases. The invention specifically relates to the ozonized oil which is orally taken for preventing and treating depressive disorder, anxiety disorder, senile dementia and parkinson disease.

Description

Control and application in nervous system disease for the ozone carburetion

Technical field

The invention belongs to pharmaceutical technology field, by ozone carburetion be used for the prevention of nervous system disease, treatment and with treatment The drug combination of nervous system disease agent.Specifically related to ozone carburetion prevents and treats depression, anxiety by oral route Disease, senile dementia, parkinson disease.

Background technology

Velio bocci outlines in " ozone therapy " book and can play many using the ozone gas of low dosage Beneficial functions, and have no side effect, i.e. ozone therapy (" the oxygen-ozone therapy " writing see velio bocci, Beijing University Hospital publishing house, 2004).Ozone therapy can be realized by multiple route of administration, and produces not for various disease Same effect.Ozone carburetion external is used for the treating for skin disease medicine such as decubital ulcer and ulcer as antibacterial, deodorizer.Therefore, Know that ozone has oxidation and antibacterial action.Direct for ozone carburetion gavage is used for controlling of the gastritis that helicobacter pylori causes Treat.Muscle or subcutaneous injection ozone gas are treating slow viruss hepatitis and vascular conditions.Vagina is passed directly into ozone gas Inflammation and bacterium infection can be cured.Ozone gas are directly mixed in vitro with the blood of certain volume, then feed back to patient It is referred to as autologous hemotherapy, human internal environment can be nursed one's health, reduce sensitivity and the enhancing human body immunity power of body.Rectum is direct Blowing ozone's gas can improve Parkinsonian symptom (see lamberto re, mohamed n. mawsouf, silvia Menendez, olga s. leon, gregorio m. the sanchez, " ozone that and frank hernandez writes Therapy:clinical and basic evidence of its therapeutic potential ", archives Of medical research, 2008,39:17-26).Abdominal cavity can cardioprotection obstruct from Acute myocardial to ozone gas Damage (clara di filippo, margherita luongo, the raffaele marfella, franca of plug Ferraraccio, biagio lettieri, annalisa capuano, francesco rossi, michele d' " the oxygen/ozone protects the heart from acute myocardial infarction that amico writes through local increase of enos activity and endothelial progenitor cells Recruitment ", naunyn-schmied arch pharmacol, 2010,382:287 291).From structure, although Ozone carburetion and ozone gas (: o-o-o) it is not same substance, but ozone carburetion is by obtaining to oily addition ozone, Therefore there is ozonide structure in the molecule thereof, the functional similarity with ozone gas.Any of the above route of administration all shows ozone Directly can be absorbed by organisms in the way of gas and function.The function of ozone gas may by three below approach Lai Realize: (1), ozone pass through biochemical reaction in vivo, generate material (the hydroxyl radical free radical oh of similar active oxygen^-, super oxygen cloudy Ion o₂ ^-Deng), extensively affect body oxidation-reduction system；(2), ozone can cause endothelial progenitor cells to assemble and promote an oxygen Change the generation of nitrogen (no), play vasodilatory effect；(3), ozone can inducing bone marrow stem cell to vascular injury site, promote Enter injured blood vessel reconstruction, but concrete mechanism is still not clear.

There is many defects in above-mentioned route of administration: contact with too many material on the way it is difficult to ensure that gas enters having of body Effect concentration.If giving the excessive body that easily induces to produce uncomfortable reaction, and operating process being loaded down with trivial details, along with the course for the treatment of is longer, patient Difficult to accept.Especially autologous hemotherapy, 2～3 times weekly, continuous 10 weeks be a course for the treatment of.The present invention is with oil and ozone addition Mode, obtains ozone carburetion, then this oil is wrapped up with enteric coated capsule, can overcome the shortcomings directly using ozone gas. Both ensured that ozone carburetion was not contacted with extraneous any material, also can preserve steadily in the long term under normal conditions；Can also fixing quantity ozone Carburetion enters body, thus avoiding being administered by other administering modes, artificially causes dose improper.Ozone carburetion enteric coated capsule Route of administration is directly to be administered orally, and body is injured minimum, operation is simple, is convenient for carrying, and has established good for its popularization Basis.

In ozonisation oil product, ozonisation olive oil, sunflower oil, soybean oil are used for decubital ulcer as antibacterial, deodorizer List with the topical drug of the treating for skin disease such as ulcer.But the form that ozone carburetion is made enteric coated capsule is passed through directly Oral mode enters body and produces effect, there is no report at present.In the present invention, by ozone carburetion enteric is directly administered orally Capsule, the mode of lumbar injection, coloclysis, gavage, intravenous injection, subcutaneous injection, intramuscular injection and suppository, medicine can be produced and make With.

The pathogenesis of senile dementia (also known as alzheimer's disease) are still unclear so far.Medicine master in the market The medicine of cholinergic function to be increased, such as cholinesterase inhibitor galantamine, donepezil (Aricept), m receptor agonism medicine Xanomeline etc., these medicines are only capable of delaying pathogenic process, but can not cure senile dementia, and with cardiovascular and gastrointestinal Road side effect.And other conventional medicine such as medicines such as antidepressant, anxiety, sedative hypnotic, psychosis are to old age The symptom improvement of dementia is limited, and has the side reaction of nervous system.In consideration of it, needing a kind of more efficient and safe treating The medicament of senile dementia.

The technical problem to be solved is for above-mentioned state of the art, provides and can effectively alleviate old being crazy about Slow-witted disease symptom, slows down the Memory Impairment of senile dementia, slows down the cognitive dysfunction of senile dementia, prevents old silly A kind of medicament for treating senile dementia of the neuronal damage that slow-witted disease leads to.

Parkinson disease (pd) also known as Parkinsonism, are one of modal neurodegenerative diseases.Main disease clinically Reason change is that substantia nigra of midbrain compact part dopamine (da) serotonergic neuron is optionally dead, lacks, and leads to striatum da not enough, from And lead to the disorder of Basal ganglia dysfunction of nervous regulation, the cause of disease of its morbidity is not yet clear so far.But research channel syndrome Reality, this disease has substantial connection with oxidative stress and mitochondrial function exception etc., and therefore, mitigating oxidativestress damage can conduct Drug target is treating parkinson disease.Additionally, up-to-date research shows, ozone can improve the nervous system such as parkinson disease and move back The clinical symptoms of row disease, show clear and definite anti-oxidation protection effect, and have certain effect in terms of neuroprotective. The black substance dense area apoptosis of Parkinsonian, are the important pathologic basis of this disease, suppress this kind of apoptosis, this disease is controlled Treat and also can play a positive role.Ozone, because it is universally present in common air, has multiple biological activities, such as: Cardiovascular protective effect, antioxidation, uvioresistant and radiation resistance, antimutagenic and antitumaous effect, antibacterial action, antiviral Effect, blood lipid-reducing blood sugar-decreasing effect, immunoregulation effect etc..All have a wide range of applications in the field such as medication chemistry and food.

Content of the invention

The purpose of the present invention is to prevent and treat depression, anxiety neurosis, old using ozonisation oil formulation and route of administration Dementia disease, parkinson disease, prepare easy, with low cost.Verify by clinic application, the present invention has evident in efficacy, oral agents Amount is low, has no toxic side effect, the advantages of effective percentage is high.

In the present invention, why select one of various oil described in claim 1,2, two kinds and two or more, It is because that these oily unsaturated fatty acid contents are higher, wherein the unsaturated fatty acid of walnut oil up to more than 92%, in unsaturation At least one olefinic double bond in fatty acid structure.If by one of claim 1,2, two kinds and two or more containing insatiable hunger One of the oil high with fatty acid and claim 3～7, two kinds and two or more surfactants mix, also can with smelly There is additive reaction in oxygen.As long as it can be seen that there is alkene unsaturated bond in the structure of addition product with ozone, additive reaction can occur, Unsaturated bond number is more, and reaction is more susceptible to, and more with the amount of ozone addition, and addition product can carry ozone molecule Number is also more.

For reaching above-mentioned purpose, the technical solution used in the present invention will be carried out with reference to following Making programme and embodiment Simple illustration.

1st, ozone gas are prepared.

2nd, prepare ozone carburetion.

3rd, prepare ozone carburetion enteric coated capsule.

4th, the ozone carburetion containing surfactant for the preparation.

5th, the ozone carburetion enteric coated capsule containing surfactant for the preparation.

6th, the preventing and treating experiment of ozonisation olive oil Capsule on Senile dementia.

7th, the preventive and therapeutic effect to depression for the ozonisation Fructus Canarii albi oil capsule.

8th, the preventive and therapeutic effect of disease is considered in the focusing of ozonisation Fructus Canarii albi oil capsule.

9th, the preventive and therapeutic effect to Parkinson's disease for the ozonisation Fructus Canarii albi oil capsule.

Specific embodiment

Following non-limiting examples are used for the present invention is described.

Prepared by embodiment 1 ozonisation olive oil enteric coated capsule

1st, ozone gas are prepared.The present invention prepares ozone gas using medical oxygen by ozonator.

The dro3-a type ozone machine (power 55w) producing selected from Xi'an Derun Bio-Technology Co., Ltd.'s design.

2nd, prepare ozone carburetion and ozone carburetion enteric coated capsule whole process need carry out at 20～25 DEG C it is ensured that ozonisation Oil will not occur pyrolytic reaction.

3rd, olive oil 3kg inserts in reactor；Ozone is with 150m³/ h flow velocity adds, and total reaction time is 20 hours.Reaction After end, residual air inactivates.

4th, obtaining ozonisation Fructus Canarii albi oil concentration is 40 mg/l, and 25 DEG C can stably preserve ten months.

5th, prepare ozonisation olive oil enteric coated capsule.

(1), the preparation of capsule material: the ratio by weight 3:3:1:1 weighs water, gelatin, glycerol and glutinous rice flour or starch falls Enter in glue tank, during colloidal sol, temperature is first arranged to 75 DEG C, start to add water when temperature reaches 60 DEG C, add water 10 minutes, use handss Touching has micro- boiling hot sensation, is initially added into glycerol, stirs 2 minutes, takes 2 times from glue pot bottom, refund in glue tank, rapidly plus gelatin, Mixing time is 2 hours, and after stirring, temperature is set as 60 DEG C, standing de-bubbled 8 hours.

(2), pressing is adopted to prepare ozonisation olive oil enteric coated capsule, capacity 0.25ml.

22 DEG C of glue capsules of room temperature, rubber thickness is 0.7mm, and capacity is 0.25ml, and prepared soft capsule cools down 8 in rotating cage Hour, come out of steamer, be drying to obtain ozonisation olive oil enteric coated capsule, standby in 4 DEG C of lucifuge cold preservations.

The enteric coated capsule preparation of embodiment 2 ozonisation olive oil, soybean oil and Oleum Arachidis hypogaeae semen miscella

3rd, olive oil 1kg, soybean oil 1kg and Oleum Arachidis hypogaeae semen 1kg insert in reactor；Ozone is with 150m³/ h flow velocity adds, always Response time is 20 hours.After reaction terminates, residual air inactivates.

4th, obtaining ozonisation miscella concentration is 40mg/l, and 25 DEG C can stably preserve ten months.

5th, prepare ozonisation miscella enteric coated capsule.

(2), pressing is adopted to prepare ozonisation miscella enteric coated capsule, capacity 0.25ml.

22 DEG C of glue capsules of room temperature, rubber thickness is 0.7mm, and capacity is 0.25ml, and prepared soft capsule cools down 8 in rotating cage Hour, come out of steamer, be drying to obtain ozonisation miscella enteric coated capsule, standby in 4 DEG C of lucifuge cold preservations.

Embodiment 3 contains the ozonisation olive oil enteric coated capsule preparation of surfactant

3rd, olive oil 3kg inserts in reactor, is slowly added to sorbitan monooleate polyoxyethylene ether (Tween 80) 20ml, mixes, ozone is with 150m³/ h flow velocity adds, and total reaction time is 20 hours.After reaction terminates, residual air inactivates.

5th, the ozonisation olive oil enteric coated capsule containing surfactant for the preparation.

22 DEG C of glue capsules of room temperature, rubber thickness is 0.7mm, and capacity is 0.25ml, and prepared soft capsule cools down 8 in rotating cage Hour, come out of steamer, be drying to obtain the ozonisation olive oil enteric coated capsule containing surfactant, standby in 4 DEG C of lucifuge cold preservations.

Embodiment 4 contains the ozonisation olive oil enteric coated capsule preparation of surfactant and cosurfactant

3rd, olive oil 3kg inserts in reactor, is slowly added to sorbitan monooleate polyoxyethylene ether (Tween 80) 20ml and straight alcohol 20ml, mixes, ozone is with 150m³/ h flow velocity adds, and total reaction time is 20 hours.After reaction terminates, remaining Gas inactivates.

5th, the ozonisation olive oil enteric coated capsule containing surfactant and cosurfactant for the preparation.

22 DEG C of glue capsules of room temperature, rubber thickness is 0.7mm, and capacity is 0.25ml, and prepared soft capsule cools down 8 in rotating cage Hour, come out of steamer, be drying to obtain the ozonisation olive oil enteric coated capsule containing surfactant and cosurfactant, in 4 DEG C of lucifuges Cold preservation is standby.

The preventing and treating experiment of embodiment 5 ozonisation olive oil Capsule on Senile dementia

The present invention solves the technical scheme that above-mentioned technical problem is adopted

1st, laboratory animal:

Experiment is using male icr mice, body weight 22-28g.It is divided into 4 groups, Normal group, a amyloid beta (a β) group is smelly Oxidation olive oil administration group 2.5mg//d empty stomach gavage, a β and ozonisation Fructus Canarii albi oil capsule administration group, every group 8.Daily Test period is fixed on 9:00am-4:30pm.Experimental implementation follows nih laboratory animal guide for use (nih publications No.80-23,1996).

2nd, the foundation of senile dementia animal model:

To injected in mice chloral hydrate, dosage 10mg/kg, anaesthetized, be fixed on stereotaxic instrument, cut head hair, Expose skin, with the midpoint of two lines as starting point, one otch is cut off for terminal, before exposure in the midpoint of two ear trailing edge lines Halogen, with bregma as zero, retreats 1.5 mm, opens 1.2mm by left and right, this two points are the coordinate in Hippocampus cal area, bore Hole, inserting needle 1.5mm, inject a β l μ g, matched group and ozonisation olive oil administration group injecting normal saline, skin suture, sterilize, Put back to and raise in cage.

3rd, it is administered:

Model is set up after completing, matched group injecting normal saline, and the administration of ozonisation olive oil takes gavage 2.5mg//d, often It is administered once on an empty stomach, is administered continuously 14 days, carries out behavioristicss' inspection afterwards.

4th, behavioristicss' inspection (water maze laboratory) of learning and memory ability:

Water maze device is a circular black pond, diameter 110cm, high 50cm, and the inside fills water, depth of water 24cm, water temperature 22-24 DEG C, at the 1cm of underwater, there is the platform of a diameter 8cm, the curtain that peripheral pool has black blocks, and surrounding hangs with visible So that mouse memory locality, water maze is artificially divided into 4 quadrants to label, and training all enters mice from different quadrants every time Water, 4 quadrants terminate as a cycle of training, mice free swimming in water, until finding platform, if in mice 90 seconds no Method finds platform, then artificially guiding mice, to platform, allows it to stop on platform 15 seconds.The daily training of every mice 8 times (2 Cycle), continuous training 4 days.5th day, remove underwater platform, quadrant puts into mice from original platform opposite, allows it in water maze Free swimming 60 seconds in device.Using video monitoring system tracking picture-recording.After experiment terminates, software analysis mouse movement track.

5th, the inspection (new object identification) of cognitive competence:

New object identification experiment is carried out in a homemade white plastic behavior case, and the length, width and height of behavior case are respectively 50*50* 30cm, 33 days stages of whole experiment point complete.First stage, the 1st day laundering period, mice is put into and allows it in behavior case freely Explore 5 minutes, in this stage, there is no data collection.Second stage, the 2nd day training period, two identical objects are placed into row For in case, object distance behavior case about 5cm, two objects, at a distance of 20cm, are put into mice and allow it freely explore 5 minutes.We Exploratory behaviour is defined: the nose of mice touches object apart from object less than 2cm or with nose.Walk around object Move or lie prone and cannot function as exploratory behaviour in its near vicinity.In this stage, record mice and explore, the time of each object, knot Shu Hou, mice puts back to original cage at once.Phase III, the 3rd day test phase, mice is put back into original behavior case and freely explores 5 minutes, one of object changed a new object into.Weigh the cognitive function of mice, resolving index=spy using resolving index The time of Suo Xin object/(exploring the time of the time+exploration past heritage body of new object).

6th, statistical analysiss are processed

The data of this part is all represented with the form of mean ± sd (mean ± standard deviation).Data variance analyses (one-way anova).It is statistically significant that p < 0.05 is set to significant difference.

Experimental result:

(1) ozonisation Fructus Canarii albi oil processing improves senile dementia model mice Spatial learning and memory (as shown in table 1):

The 4th day training period, measure the time that mice flees from platform from water, after injection a β mice find platform spend longer Time.After ozonisation olive oil gavage (2.5mg//d), the time that mice finds platform substantially shortens (p < 0.05).? 5 day probe phase, the platform of the second quadrant is removed by we, to detect the memory ability of mice.Result shows, a β mice is second The distance of quadrant is considerably less than Normal group (p < 0.0l), and after a β injection, ozonisation olive oil gavage group is spent more than a β injection group Many time is at the second quadrant (p < 0.0l).The number of times statistics that mice is passed through with original position of platform finds, stereotaxical injection a After β, the number of times that mice passes through original position of platform is considerably less than normal group (p < 0.0l), after ozonisation olive oil gavage, mice The number of times passing through original position of platform substantially increases (p < 0.0l).

The impact to senile dementia model mice Spatial learning and memory for the table 1 ozonisation olive oil

Compare with model group, * * p < 0.0l

(2) ozonisation Fructus Canarii albi oil processing improves senile dementia model mice cognitive function (as shown in table 2):

Explore the time scale of new and old object by new object identification experiment test mice.Resolving index=identification object 1 when Between/(identification object 1 time+identification object 2 time), find in table 2 that mice explores the resolving index of two same object with always The exploration time is of substantially equal, compares that there was no significant difference between each group.Show in table 2 that (object 1 changes test phase mice to new object Become one before not in contact with the new object crossed, object 2 is constant) resolving index.In the test phase, the resolving index of a β mice is more right Reduce according to group, difference is statistically significant;The resolving index of ozonisation Fructus Canarii albi oil processing mice significantly raises compared with a β mice.Respectively Group and a β positioning group compare, and difference is statistically significant;After a β positioning group gavage ozonisation olive oil, resolving index compares compared with a β Group improves.

The impact to senile dementia model mice cognitive function for the table 2 ozonisation olive oil

Compare with model group, * p < 0.05

Conclusion: ozonisation olive oil can be effectively improved Memory Impairment and the cerebral damage of senile dementia.Cause This, the medicament for treating senile dementia of the present invention has significant clinical meaning and using value.

Highly preferred embodiment of the present invention illustrates, and the various change made by those of ordinary skill in the art or remodeling are not Can depart from the scope of the present invention.

Relevant clinical experimental data is as follows:

1st, clinical data

1.1 data are selected from 2013 2 months in December, 2015 patients 50, with the ratio of 1:l be randomly divided into treatment group with right According to group each 25.Wherein treatment group man 20, female 5;Age 60-80 (67.2 ± 5.4) year;Course of disease 1-12 (4.4 ± 1.3) Year;Symptom score 10-28 (16.1 ± 1.6) point.Matched group man 18, female 7;Age 62-85(68.9 ± 4.5) year；The course of disease 1-10 (4.2 ± 1.4) year;Symptom score 11-28 (17.2 ± 1.7) point.Two groups of patients are in sex, age, the course of disease, state of an illness etc. There was no significant difference (p > 0.05) through statistical analysis for physical data, has comparability.

2nd, diagnostic criteria

The dull-witted diagnosis mark of American Psychiatry disease association fourth edition " psychotic diagnostic and statistical manual (dsm-iv) " person in middle and old age's property Accurate.

(1) occur many-sided cognitive defect, be changed into following both:

A. memory defects (ability of study fresh information is impaired or can not recall the former information acquired)；

B. one of at least following cognitive disorder: (1) aphasia (2) agnosia (3) apraxia (4) executes the obstacle of operating capability；

(2) above-mentioned performance leads to the defect of social activity or occupational function, and can find that these functions are substantially not so good as in the past;

(3) the onset feature of the course of disease is gradually onset, continuous downturn；

(4) above-mentioned cognitive defect is not caused by underlying cause；

A. other lead to memory or central nervous system's situation of cognitive progressive defect, such as: cerebrovascular etc.

What b. reason was bright leads to the general disease of dementia；

(5) caused by not due to delirium；

(6) caused by not due to Serious depression and schizophrenia；

3rd, inclusive criteria:

(1) meet Americanism obstacle to dull-witted clinical criteria, mmse scoring all 10-24/, schooling is equal More than junior middle school, belonging to light moderate senile dementia, will be with seriousness patient with nervous system disease, seriousness cardiopulmonary, Liver and kidney disease Disease is all excluded;(2) all with dysmnesia, the symptom such as apraxia and judgment obstacle;(3) age is in 60-85 year;(4) agree to ginseng Plus experiment, sign Informed Consent Form.

Exclusion standard: 1. the age is below 60 one full year of life or 85 one full year of life above person;2. it is associated with cardiovascular, lung, liver, kidney and make The severe primary disease patient such as blood system;3. psychotic;It is 4. all that by regulation medication or data, congruent affecting the treatment is not sentenced Disconnected person.

4th, therapeutic scheme

4.1 matched group patients all give donepezil hydrochloride (Tianjin Li Sheng pharmaceutcal corporation, Ltd produces, every 5mg) 5mg, before sleeping 10min is administered orally.

Ozonisation Fructus Canarii albi oil capsule of the present invention is taken by 4.2 treatment groups, and on an empty stomach, 1 every time, once a day, 90 days be a treatment Journey, counts two groups of curative effects after a course for the treatment of.

4.3 curative effect determinate standards are according to " diagnosis of senile dementia, differentiation of symptoms and signs for classification of syndrome and efficacy assessment standard ":

Effective: cardinal symptom is recovered substantially, sanity, accurate positioning, answer a question correct, be quick on the draw, take care of oneself, energy Carry out mass society activity;

Effective: main spirits symptom has mitigated or partial disappearance, life is basic to take care of oneself, and answers a question and is in the main true, but reaction Blunt, intelligence, personality still have obstacle;Control: main spirits state no increases, situation of taking care of oneself change is inconspicuous, reaction is late Blunt, intelligence, personality still have obstacle but no increase;

Invalid: cardinal symptom no changes, the state of an illness has development can't take care of oneself, and answers a question incorrect, mental dementia.

Treatment always effectively=(effective+effective)/total number of persons.

5th, statistical procedures

5.1 efficacy evaluations: using intelligent comprehensive point system, (1) memory (6 points);(2) orientation force (4 points);(3) ability of thinking (4 points);(4) computing power (4 points);(5) affective activity (3 points);(6) two just function (3 points) (7) activity of daily living (4 points).

5.2 efficacy assessment standards: efficacy evaluation is carried out according to mmse scoring increase and decrease situation after treating before patient's treatment.Curative effect Index: integration x 100% before (integration before integration-treatment after treatment)/treatment.

Effective therapeutic index >=20%

Effectively treatment index >=12%

Futile treatment index < 12%

Deteriorate therapeutic index < -12%

Curative effect judging standard

Effective integration increases > 8 points or reach 28 points;

Effective integral increases 4-7 and divides;

Invalid integration increases < 3 points.

All cases through one course for the treatment of of ozonisation olive oil capsule for treating of the present invention, before and after being treated by above-mentioned standard Compare, to judge curative effect.It is shown in Table 1.

1 liang of group Clinical efficacy comparison example (%) of table

Note: compare with matched group, * p < 0.05

6th, conclusion

Abundant raw material of the present invention, cheap, effective for treating senile dementia, good effect, drug safety, there is clinical meaning Justice.

The preventive and therapeutic effect to depression for the embodiment 6 ozonisation Fructus Canarii albi oil capsule

Incidence of depression is very high at this stage, common with brain worker.Social elite that is ambitious, shouldering heavy responsibilities, It is susceptible to suffer from this disease, it industry is more common.Teenager is also added thereto in a large number.Electronic product is popularized, and uncontrolled use, to this Disease has acted the effect of adding fuel to the flames.This disease concealment, medically detection meanss shortage, patient is dog-tired, merely desires to ask dead, is not desired to ask Doctor, people is difficult to discover again at one's side, is neglectful in taking precautions.According to World Health Organization's statistics, it is the fourth-largest that depression has become as the world at present Disease.Expect the year two thousand twenty, be likely to become and be only second to the second largest disease of the cardiopathic mankind.Medical expert is had to claim, depression is such as Fruit is not treated, or controls inadequate, and 30% can suffer First-episode, but can show effect again after a while again;30% drag into chronic, Delay lifelong;30% commits suicide and die.At this moment look for psychologist to convince by patient analysis or allow patient suitably to rest, be not solve problem Main method.The task of top priority is intended to carry out correct righting conditioning and treating to patient, improves body interior environment, it appears extremely Important.The purpose of the present embodiment is to provide a kind of ozone carburetion of specific treatment depression.

First, clinical efficacy

1st, physical data

Treatment case 50.

2nd, therapeutic effect

Subjective symptomss curative effect: cure 40, effective 8, invalid 2, total effective rate 96 %.

It is below the several Typical cases using ozonisation Fructus Canarii albi oil capsule, daily on an empty stomach one a time, 3 months 1 courses for the treatment of.

Medical record 1:

What so-and-so, female, 46 years old, teacher, first visit in 1989.Patient is engaged in teaching job one's early years, and mental work intensity is very big, brain It is chronically at extremely tired state so that patient suffers from depression in three teens, lasts the more than ten years, period commits suiside not for 2 times Then.Afterwards with this ozonisation olive oil capsule for treating, on an empty stomach, 1 every time, once a day, 90 days be a course for the treatment of.Took at 3 months Afterwards, diet sleep recovers normal quickly.Tired, depressed, pessimistic and worldweary sensation does not occur again.Familiar therewith have together per capita Sense, its people becomes optimistic talkative.Appetite, sleep, the mental status are good all the time.

Medical record 2:

Thank so-and-so, man, 51 years old, civil servant, first visit in 2004., often using computer, extended sleep appetite is poor, often feels tired for patient Labor.Take this ozonisation olive oil capsule for treating, on an empty stomach, 1 every time, once a day, 90 days be a course for the treatment of.Took at 3 months Afterwards, recover.

Medical record 3:

Suddenly so-and-so, female, four teens, office worker, first visit in 2006.Patient's cesarean in 2003, before computer, task is numerous at ordinary times Weight, suffers from depression in 2005.Afterwards with this ozonisation olive oil capsule for treating, on an empty stomach, 1 every time, once a day, 90 days be one The individual course for the treatment of.After taking at 3 months, recover.Symptom of shaving one's head and on the face mottle also disappear simultaneously.

The preventive and therapeutic effect of disease is considered in the focusing of embodiment 7 ozonisation Fructus Canarii albi oil capsule

It is used for the present invention is described below in conjunction with non-limiting example.

Ozonisation olive oil capsule for treating anxiety neurosis clinical research

1 general data: ozonisation Fructus Canarii albi oil capsule is applied to clinical observation anxiety neurosis case 100, wherein man 55, and female 45 Example, age 23-62 year.The course of disease the shortest person's half a year, elder reaches 3 years, average 1.5 years.

2 diagnostic criterias: clinical manifestation (1) mental maladjustment: subjective doubt, lather, sensitive excitation, attention do not collect In, terrified very much, dying sense.(2) somatization: xerostomia, uncomfortable in chest, tachycardia, frequent micturition, diarrhoea, constipation, shake perspiration, the heart Throb with fear, dyspnea.(3) motor symptoms: hand shaking, muscular tone, uneasily walk up and down.(4) typing: generalized anxiety disorder and terrified Outbreak clinic can have acute and chronic two classes.Diagnosis basis: (1) generalized anxiety disorder 1. undue anxiety persistent period is in half a year More than;2. with vegetative nerve function is hyperfunction, mobility is uneasy and too vigilant;3. obsession, phobia, depressibility are not met Neurosal diagnostic criteria, and anxiety not organic disease causes.(2) 1. no obvious cause suddenly panic attack occurs Strongly terrified, with dying sense or sense out of control;With serious vegetative nerve symptom when 2. showing effect;3. outbreak of short duration (every time As be less than 2 hours), outbreak significantly affect routine work;4. at least show effect 3 times within 1 month;5. it is important to note that excluding first shape Adenohypersthenia and adrenal gland's chromaffin cell tumor, cardiovascular diseasess, spontaneous hypoglycemia, endocrinopathy, drug withdrawal reaction and temporo Similar outbreak caused by leaf epilepsy.6. do not meet the diagnostic criteria of hysteria and phobia.7. electroencephalogram shows that x activity reduces, b activity Increase.

3 test methods: ozonisation Fructus Canarii albi oil capsule clinical sample, specification is grain 0.25ml, three months is a course for the treatment of, one day Once, early (medicine) being taken before meal is used.2 courses for the treatment of of treatment.

4 criterions of therapeutical effect: (1) recovery from illness: clinical symptom disappearance, normal work and work can be participated in.(2) take a turn for the better: clinical symptoms Mitigate.(3) invalid: symptom is no improved.

5 therapeutic effect: be shown in Table 1

1 liang of group comparitive study of table

It can be seen that, the medicine that the present invention is obtained safely and effectively can treat anxiety neurosis, and has no toxic side effect.

The preventive and therapeutic effect to Parkinson's disease for the embodiment 8 ozonisation Fructus Canarii albi oil capsule

The treatment to mouse model of Parkinson's disease for the zoopery ozonisation olive oil

1. experiment material

1.1 experiment reagents and instrument

Rotenone (sigma), sough (dmso, sigma) for dimethyl Asia, Semen Maydis oil (Luhua Group Co., Ltd., Shandong), malonaldehyde (biological engineering is built up in Nanjing to be had for content and superoxide dismutase, glutathion peroxidase and hydroperoxidase reagent box Limit company).It is pure that remaining reagent is domestic commercially available analysis.

1.2 animal models and packet

This experiment adopts the method for subcutaneous injection rotenone to build Parkinsonian mouse model.Buy bull c57bl/6 Mice 30, body weight 25-28g, provided by Chinese Academy of Sciences's Shanghai Experimental Animal Center.It is normally right that mice is divided into by body weight stochastic averagina According to group (nc group, n=10), rotenone (pd model group, n=10), ozonisation olive oil treatment group (n=10).In experiment, by Radix seu Caulis Derridis Trifoliatae Ketone is first dissolved in the dmso of extremely low volume, is then dissolved in Semen Maydis oil (being made into 2mg/ml oil solution).Rotenone group (pd model group) is every Day, Normal group (nc group) was in the subcutaneous note of nape part in nape part subcutaneous injection rotenone oil solution (3mg/kg Mouse Weight) Penetrate isopyknic Semen Maydis oil (dmso containing respective volume), ozonisation olive oil treatment group is daily in nape part subcutaneous injection Radix seu Caulis Derridis Trifoliatae Ketone, simultaneously according to dosage 2.5mg/ only/d empty stomach gavage ozonisation olive oil.The free diet of all mices and drinking-water, temperature during experiment 25 ± 2 DEG C of degree, relative humidity (65 ± 15) %.Daily animal general state of observing shows and records animal behavior change, continues 5 Week.

2. test Testing index

2.1 wmt-200 water are got lost

Wmt-200 water gets lost video analytic system (Chengdu TME Technology Co., Ltd.) using computer vision related algorithm, real When follow the tracks of the behavior state of animal, and analyze and record after animal enters water the time needed for search target: before experiment, mice is put Adapt to 20s on platform, subsequently mice is faced the wall and meditated from different quadrants at random and insert in pond, mice terminates note after climbing up platform 5s Record, the longest record time is that 30s (if can not appear on the stage in 30s, climb up platform and adapt to 10s, finally dries mice and puts by guiding mice People's mouse cage).So mice is inserted swimming pool, be 1 group 5 times, measure the average slip time of four groups of mices respectively, empty to evaluate it Between learning capacity.Tested by above-mentioned steps within the 2nd, 3,4 and 5 week after experiment process.

2.2 oxidative stress Indexs measure

After 5 weeks behavioral value, brain is taken using the rapid broken end of de- cervical approach, substantia nigra of midbrain and striatum is rapidly separated out on ice face, Glass homogenizer makes 10% tissue homogenate, -80 DEG C of Refrigerator stores.With bca standard measure albumen during experiment, illustrate according to test kit Book, using sod, gsh-px, cat activity and mda content in chemical colorimetry detection cerebral tissue.

2.3 statistical procedures

Using spss19.0 statistical software, p < 0.05 is statistically significant.

3. experimental result

The behavior state of 3.1 each group mices and body weight

Pd model group mice starts to occur for the 11st day lethargy from experiment, and activity is slow, and hair is loose and matt, and appetite is bright Aobvious go down, start in succession to occur within the 17th day body flexing, hypokinesia, when and with tetanic, performance of trembling, display parkinson Typical behaviour feature, shows parkinsonian mouse modeling success.Body flexing in remaining 2 groups of mice, hypokinesia, by force Directly, tremble performance.To each group mice, daily measured body weight finds, pd model group Mouse Weight increases more other each groups slowly, but The difference that compares between group that there are no significant.

3.2 each group mice substantia nigra oxidative stress indexs

The measurement result of the black substance oxidative stress index of each group mice is shown, the mice of pd model group, its determined item Biochemical indicator all deviates the value that the mice of nc group is measured.The mice items oxidative stress index of ozonisation olive oil treatment group is equal Obtain largely recovering.The result being measured is as shown in table 1:

Table 1 mice substantia nigra of midbrain oxidative stress index (x ± sd, n=10)

Compare * p < 0.05 with model group

Compare between each group of data of ozonisation olive oil treatment group and pd model group and all have significant difference (p < 0. 05).

(1) mice water lost neurobehavioral analysis

At 2nd, 3,4 and 5 weekend after experiment process, measure the average slip time of mice respectively, result shows, pd model group mice exists 3rd weekend average slip time is significantly higher than nc group (p < 0.05), and the 4th and 5 weekend differences are extremely notable (p < 0.01).And ozonisation Olive oil treatment group mice is substantially less than pd model group (p < 0.05), the 4th and 5 weekend differences in the 3rd weekend average slip time Extremely notable (p < 0.01), experiment concrete outcome is as shown in table 2:

Table 2 mice each weekend after experiment process average slip time (x ± sd, n=5)

Compare * p < 0.05, * * p < 0.01 with model group；## p < 0.01, is compared with nc group.

In sum, ozonisation olive oil can be effectively improved the pathological symptom of the parkinson mouse model of rotenone making, Reduce the toxicity of substantia nigra neuron, there is to parkinson disease the effect of prevention and treatment.

Be presented herein below patient use medicine of the present invention clinical statisticses data:

First, physical data

Accept patient 100, wherein male 62 people, women 38 people for medical treatment, in age 50-80 year, 68 years old mean age, course of disease 2-8 is not Deng.

2nd, Therapeutic Method

According to ozonisation Fructus Canarii albi oil capsule of the present invention, daily empty stomach one a time, 3 months is a course for the treatment of.

3rd, efficacy assessment standard:

1st, cure: clinical symptom disappearance, trembling of limbs, muscular rigidity, lumbering phenomenon disappear, and sensation and function of deglutition are equal Normally, life can take care of oneself;

2nd, take a turn for the better: clinical symptoms are controlled, and every physical signs have all taken a turn for the better;

3rd, do not heal: patient clinical symptom is without any improvement or even increases.

4th, therapeutic outcome statistics

It can be seen from the results above that ozonisation olive oil capsule for treating parkinson disease of the present invention have good clinical effectiveness, The cure rate for the treatment of can be effectively improved, be worth promoting in clinical practice.

Model case:

Case one, Zhu, man, 49 years old, extremity involuntary vibration occurred before patient's half a year, tremble after shifting one's position and mitigate or disappear Lose, and have slight moving obstacle, patient is diagnosed as parkinson disease, using ozonisation olive oil capsule for treating of the present invention, daily On an empty stomach one a time, it is within 3 months a course for the treatment of.After taking two courses for the treatment of, the phenomenon of patient's trembling of limbs is clearly better, muscular rigidity Phenomenon be wholly absent, again continue to take a course for the treatment of afterwards, than substantially flexible before, life can take care of oneself patient's Ambulatory Activity.

Case two, turn round and look at certain, female, 62 years old, patient household's narration suffered from parkinson disease 1 year about, deadlock of lurching on foot Firmly, there is obvious festination, patient adopts ozonisation olive oil capsule preparations treatment of the present invention, daily on an empty stomach one a time, 3 The moon is a course for the treatment of.After taking two courses for the treatment of, patient's action and linguistic competence get a promotion, and can normally exchange, limbs Flutter phenomenon is taken a turn for the better, and is continuing with two courses for the treatment of, and patient's walking and activity are all very flexible, can do some simple families Business, life can take care of oneself.

The foregoing is only presently preferred embodiments of the present invention, not in order to limit the present invention, all essences in the present invention Any modification, equivalent and improvement made within god and principle etc., should be included within the scope of the present invention.

Claims

1. a kind of control and application in nervous system disease for ozone carburetion is it is characterised in that oil is at least selected from olive oil, bean Oil, Oleum Helianthi, Semen Lini oil, Oleum Brassicae campestriss, Semen setariae oil, Semen Maydis oil, Fructus Maydis oil, Oleum sesami, Oleum Gossypii semen, Oleum Ricini, flower Oil generation, Oleum Camelliae, perilla oil, safflower oil, almond oil, hazelnut oil, walnut oil, pine-seed oil, shinyleaf yellowhorn oil, edible blend oil, One of cod-liver oil and fish oil, by oily electrophilic addition ozone, the ozone carburetion obtaining make capacity be 0.1～ The Oryza glutinosa of 0.75ml or starch material enteric coated capsule, contained with 2～100ml vial, with the dosage of 0.1 ~ 100ml, by oral administration Administration and being given by the way of lumbar injection, coloclysis, gavage, intravenous injection, subcutaneous injection, intramuscular injection and suppository, Can be used in prepare prevent and treat various nervous system disease medicine, nervous system disease be selected from depression, anxiety neurosis, Senile dementia, parkinson disease.

2. oil according to claim 1 is it is characterised in that carry out mixing two-by-two and two to the oil described in claim 1 Plant the mixing to oil, by electrophilic addition ozone, the ozone carburetion obtaining makes the Oryza glutinosa that capacity is 0.1～0.75ml or shallow lake Powder material enteric coated capsule, with 2～100ml vial contain, with the dosage of 0.1 ~ 100ml, be administered by oral route and adopt abdomen Chamber injection, coloclysis, gavage, intravenous injection, the mode of subcutaneous injection, intramuscular injection and suppository give, and can be used in preparation prevention With the medicine treating various nervous system disease, nervous system disease is selected from depression, anxiety neurosis, senile dementia, handkerchief gold Gloomy disease.

3. oil according to claims 1 to 2 is it is characterised in that pass through to select nonionic surfactant, anionic surface One of activating agent and cationic surfactant, two kinds and two or more mixing, with the oil described in claim 1～2 Any one of mixing, by electrophilic addition ozone, the ozone carburetion containing surfactant obtaining make capacity be 0.1～ The Oryza glutinosa of 0.75ml or starch material enteric coated capsule, contained with 2～100ml vial, with the dosage of 0.1 ~ 100ml, by oral administration Administration and being given by the way of lumbar injection, coloclysis, gavage, intravenous injection, subcutaneous injection, intramuscular injection and suppository, Can be used in prepare prevent and treat various nervous system disease medicine, nervous system disease be selected from depression, anxiety neurosis, Senile dementia, parkinson disease.

4. surfactant according to claim 3 is it is characterised in that be selected from glycerol unsaturated fatty acid ester, polyglycereol Unsaturated fatty acid ester, propylene glycol unsaturated fatty acid ester, sorbitan unsaturated fatty acid ester, polyoxyethylene sorbitol Acid anhydride unsaturated fatty acid ester, polyoxyethylene unsaturated fatty acid ester, mannitol unsaturated fatty acid ester, tetramethylolmethane are unsaturated Non- in fatty acid ester, sucrose unsaturated fatty acid ester, Polyethylene Glycol unsaturated alkyl ether and polypropylene glycol unsaturated alkyl ether One of ionic surface active agent, two kinds and two or more.

5. surfactant according to claim 3 is it is characterised in that be selected from unsaturated fatty acid salt, unsaturated fatty acidss Anion surfactant in alcohol sulfuric ester salt, alpha-sulfo unsaturated fatty acid ester, olefin sulphates and alkene sulfonate A kind of, two kinds and two or more.

6. surfactant according to claim 3 is it is characterised in that be selected from the monosubstituted trimethyl of unsaturated aliphatic hydrocarbyl moiety Ammonium salt, unsaturated aliphatic hydrocarbyl moiety two substituted dimethyl ammonium salt, unsaturated aliphatic hydrocarbyl moiety monosubstituted dimethyl benzyl ammonium salt, unsaturation Aliphatic group monosubstituted amine acylate, unsaturated aliphatic hydrocarbyl moiety two replacement amine acylate and n- methyl diethanolamine insatiable hunger With one kind of the cationic surfactant in fatty acid ester hydrochlorate, two kinds and two or more.

7. surfactant according to claim 3 is it is characterised in that be selected from food stage petroleum ether, Polyethylene Glycol insatiable hunger With alkyl ether, one kind of sorbitan monoesters polyoxyethylene ether surface active agent and two kinds.

8. any one ozone carburetion according to claims 1 to 7 it is characterised in that by select ethanol, propylene glycol, One of glycerol, hexanediol, butanediol, pentanediol, butantriol, hexanetriol, two kinds and two or more mixing, by electrophilic Addition ozone obtains the ozone carburetion containing cosurfactant and surfactant, makes the Oryza glutinosa that capacity is 0.1～0.75ml Or starch material enteric coated capsule, with 2～100ml vial contain, with the dosage of 0.1 ~ 100ml, be administered by oral route and adopt Given with the mode of lumbar injection, coloclysis, gavage, intravenous injection, subcutaneous injection, intramuscular injection and suppository, can be used in preparing Prevent and treat the medicine of various nervous system disease, nervous system disease be selected from depression, anxiety neurosis, senile dementia, Parkinson disease.

9. any one according to claims 1 to 8 is made ozone carburetion and its route of administration are it is characterised in that be somebody's turn to do Ozone carburetion can prevent and treat suppression with the combination therapies for the treatment of nervous system disease effectively by described approach Strongly fragrant disease, anxiety neurosis, senile dementia, parkinson disease.