CN108578678A - A kind of antiepileptic compositions and preparation method thereof - Google Patents
A kind of antiepileptic compositions and preparation method thereof Download PDFInfo
- Publication number
- CN108578678A CN108578678A CN201810226923.7A CN201810226923A CN108578678A CN 108578678 A CN108578678 A CN 108578678A CN 201810226923 A CN201810226923 A CN 201810226923A CN 108578678 A CN108578678 A CN 108578678A
- Authority
- CN
- China
- Prior art keywords
- parts
- antiepileptic
- compositions
- preparation
- compositions according
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/05—Dipeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
- A61K36/9062—Alpinia, e.g. red ginger or galangal
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
Abstract
The present invention relates to pharmaceutical composition technical fields, and in particular to a kind of antiepileptic compositions and preparation method thereof.The antiepileptic compositions include the raw material of following parts by weight：20 65 parts of magnesium valprote, 10 30 parts of L carnosines, 5 20 parts of Fructus Alpinae Oxyphyllae extract, 38 parts of PVP K30,26 parts of magnesium stearate, 3 10 parts of Brij30,28 parts of antioxidant, 16 parts of surfactant, 60 100 parts of Lactis Anhydrous；Preparation method includes major ingredient mixed processing, mixing sterilizing, compacting.The antiepileptic compositions preparation process of the present invention is simple, the effect of being suitble to industrialized production, the side reaction of current antiepileptic compositions can be reduced after medication, is improved to epilepsy.
Description
Technical field
The present invention relates to pharmaceutical composition technical fields, and in particular to a kind of antiepileptic compositions and its preparation side
Method.
Background technology
Epilepsy is a kind of the nervous system disease, be due to cerebral neuron lesion or damage and paroxysmal abnormality electric discharge cause
Of short duration cerebral disorder.Epilepsy invasion mechanism is more complicated, and the essence of breaking-out is the excessive Synchronous Radio of cerebral neuron
Electricity.And the paradoxical discharge of neuron and neurotransmitter, ion channel, cynapse plasticity, many factors such as Deiter's cells
There is substantial connection.
The treatment of epilepsy at present includes drug therapy, operative treatment, neuromodulation treatment etc., both at home and abroad controlling for epilepsy
It treats mainly based on drug therapy.Phenobarbital, dilantin sodium, carbamazepine, magnesium valprote are the lines being widely used at present
Antiepileptic, but the problems such as these drug generally existings need to take for a long time, and side effect is big.Wherein, magnesium valprote can be used for
A plurality of types of epilepsies are treated, side effect is mainly shown as the symptoms of digestive tract such as nausea,vomiting,diarrhea, sitophobia, flesh then occurs
Inability, trembling of limbs, incoordination, drowsiness, clouding of consciousness or stupor.Therefore, it is necessary to a kind for the treatment of both manifestation and root cause of disease, significant in efficacy anti-
Epilepsy drugs composition.
The patent of publication No. CN105770973A discloses a kind of antiepileptic and its preparation method and application, this is anti-insane
Epilepsy agent is by Nattokinase, red kojic rice powder, γ-aminobutyric acid, taurine, ascorbic acid, haematococcus pluvialis, blueberry powder, breast
The biotic components such as albumin powder, dietary fiber, lutein form, can be used pulvis, tablet and pulvis joint, tablet and tablet,
The mode that capsule and pulvis are used in combination.Although each group of substance for belonging to integration of drinking and medicinal herbs, without toxic side effect, avoid each
Kind of adverse reaction, but inventor needs long-term administration the study found that the antiepileptic cost is higher, can not fundamentally root
Epilepsy is controlled, and flexible drug combination mode needs to adjust for patient and symptom.
The patent of publication No. CN104147020A discloses a kind of anti-epileptic composition of medicine and preparation method thereof, by Ah Si
The tablet that woods, caffeine, sodium phenobarbital, dilantin sodium, auxiliary material wet granulation obtain has preferable therapeutic effect to epilepsy,
And it is cheap, toxicity is smaller.But the incidence of side effects of its composition remains to reach 16%, and recurrence rate after half a year of being discontinued
Reach 11.1%, illustrating it, there are certain side effects, and for the Drug combination of different primary symptom shapes, to nerve cell and
There are certain degree of harm for brain cell oxygen supply.
The present invention is short for antiepileptic compositions curative effect lasting time common at present, and there are many chronic side reactions
Defect is selected from adjusting nerve cell function, improving cell oxygen supply, enhancing cytotrophy with the antiepileptic third of wide spectrum
Valeric acid magnesium is main component, and the active constituent in conjunction used and auxiliary material and dosage are largely groped and studied,
To obtain that related side effect can be reduced and improve the antiepileptic compositions of curative effect.
Invention content
In view of this, a kind of antiepileptic compositions of present invention offer and preparation method thereof, from adjusting nerve cell, change
Kind cell oxygen supply function is set out, using wide spectrum antiepileptic magnesium valprote as main component, with N-BETA-Alanyl-L-histidine, Fructus Alpinae Oxyphyllae extract, more
Kind auxiliary material compounding, preparation process is simple, is suitble to industrialized production, the pair of current antiepileptic compositions can be reduced after medication
Reaction, the effect of raising to epilepsy.
In order to achieve the above-mentioned object of the invention, the present invention provides following technical scheme：
One of the objects of the present invention is to provide a kind of antiepileptic compositions, include the raw material of following parts by weight：Third
20-65 parts of valeric acid magnesium, 10-30 parts of N-BETA-Alanyl-L-histidine, 5-20 parts of Fructus Alpinae Oxyphyllae extract, 3-8 parts of PVP K30,2-6 parts of magnesium stearate,
3-10 parts of Brij30,2-8 parts of antioxidant, 1-6 parts of surfactant, 60-100 parts of Lactis Anhydrous.
Antiepileptic of the magnesium valprote as wide spectrum, antiepileptic action are shifted with Reverse transcriptase γ-aminobutyric acid
Enzyme is related, its metabolism can be made to reduce and improve the content of intracerebral neurotransmitter γ-aminobutyric acid, shies to various different degrees of
Fainting has different degrees of antagonism.Magnesium valprote is in intrahepatic metabolism, and through kidney excretion, the half-life period of hepatic lesion patient obviously prolongs
It is long.For a variety of side reaction symptoms being likely to occur, in order to not influence the blood concentration of magnesium valprote and the apparent change of half-life period
Change, inventor has carried out the screening and research of compounding ingredient.
N-BETA-Alanyl-L-histidine (β-alanyl-L-histidin) is the dipeptides found from skeletal muscle, is that the water solubility in organism is anti-
Oxygen agent can realize the function of stabilizing cell membrane by the peroxidating or elimination superoxide anion of block film inner lipid.
N-BETA-Alanyl-L-histidine is also simultaneously a kind of neurotransmitter, enzyme activity conditioning agent and metal ion chelation agent, can treat rheumatoid joint
Scorching, duodenal ulcer and the related inflammation of gastric ulcer.
As the common knowledge of this field, wound inflammation can cause epileptogenic focus, epileptic attack that intracerebral inflammatory can be caused anti-
It answers.N-BETA-Alanyl-L-histidine coordinates with magnesium valprote, can improve the content of intracerebral neurotransmitter, slows down and effect a radical cure related inflammation, and treatment is insane
The related symptoms of epilepsy, additionally it is possible to improve cell oxygen supply function, to provide neurotransmitter in vivo, reduce inflammation caused by magnesium valprote
The side reaction of class.
Fructus alpiniae oxyphyllae is the fruit of zingiberaceous plant intelligence development.Acrid flavour is bitter, returns spleen kidney channel.Pungent person dissipates, and bitter person lets out, promoting blood circulation of working hard
Dissolving stasis is conducive to cerebrovascular blood supply and supplies oxygen.Return kidney channel, kidney qi is solid, and kidney is the mother of liver, then increases the store blood function of liver, make up
Deficiecny of liver-YIN keeps qi-blood circulating normal.
Modern pharmacology research shows that fructus alpiniae oxyphyllae is rich in taurine, choline, tyrosine, 22 carbon especially contained by it
The nutritional ingredients such as acid (DHA) are all the substances for increasing neurotrophic, there is improvement to sleep, adjust human endocrine,
The effect of intelligence promoting and tranquilization.
The extract of fructus alpiniae oxyphyllae is used in combination with magnesium valprote, and nutriment can be provided for nerve cell, improves kidney
With the function of liver, keep qi-blood circulating smooth, reduces magnesium valprote to related side effect symptom caused by liver and kidney.
Become larger in view of poor fluidity, hardness after magnesium valprote moisture absorption, causes to store and using process inconvenience.Inventor passes through
Excessive quantifier elimination and screening choose magnesium stearate, Brij30 as lubricant, choose PVP K30 conduct
Adhesive chooses the good Lactis Anhydrous of mobility, compressibility as filler, and to antioxidant, surfactant and its dosage
It is screened, obtains the antiepileptic compositions, good fluidity is not easy to moisture absorption to be hardened, and stability is good.
Preferably, the antiepileptic includes the raw material of following parts by weight：32-40 parts of magnesium valprote, N-BETA-Alanyl-L-histidine 16-
23 parts, 10-15 parts of Fructus Alpinae Oxyphyllae extract, 4-6 parts of PVP K30,3-5 parts of magnesium stearate, 5-8 parts of Brij30,
4-7 parts of antioxidant, 2-4 parts of surfactant, 70-88 parts of Lactis Anhydrous.
Preferably, the antioxidant is butyl anisole, butyl hydroxytoluene, ascorbic acid or sodium sulfite.
Preferably, the surfactant is triglycerin aliphatic ester, fatty acid sorbitan or poloxamer.
Preferably, the preparation method of the Fructus Alpinae Oxyphyllae extract is specially：Full fructus alpiniae oxyphyllae is chosen, shell is removed,
It is put into the sodium chloride solution of 0.2-0.6wt% and impregnates 10-16h, taking-up drains, and after grinder is fully ground, is added 3-5 times and weighs
70% ethyl alcohol of amount, stirs evenly；Slurries are boiled by slow fire 40-60mi n, 100-200 mesh filter-cloth filterings；It is equal that filtrate is placed in high pressure
In matter machine, under 10-15MPa pressure after homogeneous, 110-120 DEG C of high-temperature sterilization, dry, ultramicro grinding obtains.
Modern pharmacology research proves that fructus alpiniae oxyphyllae ethanol extract has protective effect to mouse nerve, to glutamic acid excitement
Neural cell injury caused by toxicity is significantly reduced effect, and can effectively inhibit the nerve of glutamate excitotoxicity induction
Apoptosis.Fructus alpiniae oxyphyllae is soaked in the sodium chloride solution of partial neutral by the present invention first, vegetable protein can be made to expand, and is easy
It is dissolved out, is conducive to absorption of human body；Be ground later, alcohol extracting, decoction, filtering, homogeneous, sterilizing, drying, ultramicro grinding, work
Skill reasonable design is accurate, can make active constituent such as daucosterol, daucosterol palmitate, β-in fructus alpiniae oxyphyllae to the maximum extent
Sitosterol, yakuchinone etc. are broken to be released, and is played protection nerve, strengthen immunity, is alleviated the effect of epilepsy.
It is a further object of the present invention to provide the preparation methods of above-mentioned antiepileptic compositions, include the following steps：
1) major ingredient mixed processing：Magnesium valprote, N-BETA-Alanyl-L-histidine, Fructus Alpinae Oxyphyllae extract are weighed, after mixing in 20-30 DEG C,
200-300 mesh sieve is crossed, is fitted into hermetic bag, 10-15 DEG C of freezen protective is spare；
2) mixing sterilizing：Weigh magnesium stearate, Brij30, antioxidant, surfactant, Lactis Anhydrous,
PVP K30 is added in the major ingredient of freezen protective, is uniformly mixed, and crosses 60-80 mesh sieve, and 80-90 DEG C of instantaneous sterilizing 3-6s is obtained
Mixture；
3) it suppresses：It is using powder direct pressure closing that mixture is tabletted.
The present invention has selected master according to the physico-chemical property of each raw material and auxiliary material in antiepileptic compositions and compounding characteristic
The step of material mixed processing, mixing sterilizing, powder vertical compression, prepares the antiepileptic compositions, reasonable design, major ingredient it is cold
Freeze to vacuumize to preserve and can protect the active constituent of Fructus Alpinae Oxyphyllae extract to the maximum extent, magnesium stearate, polyoxyethylene in auxiliary material
Lauryl alcohol can keep bonding and the mixing of major ingredient, antioxidant as lubricant, stable PVP K30 as adhesive
It can ensure the antioxidant of active constituent with surfactant, and slowly release active constituent in vivo, play therapeutic effect.
Preferably, the step 1) needs to do vacuumize process after being packed into hermetic bag.
Preferably, the steam pressure of the step 2) instantaneous sterilizing is 0.5-0.7MPa, drop temperature is less than 55 DEG C.
Preferably, the piece weight for the tablet that the step 3) is pressed into is 200-220mg.
The invention has the advantages that：
1, antiepileptic compositions of the invention, wide magnesium valprote is composed with anti-epileptic, is provided neurotransmitter, is improved carefully
Born of the same parents supply oxygen the N-BETA-Alanyl-L-histidine of function, and it is main component to inhibit the fructus alpiniae oxyphyllae alcohol extract of nerve cell apoptosis, and auxiliary material selects lubricant, resists
Oxygen agent, surfactant, proportioning is scientific and reasonable, is prepared using powder direct pressure closing, and preparation method is simple, is suitble to industry metaplasia
Production, to epilepsy the effect of, are notable, and total effective rate can reach 95%, Small side effects.
2, antiepileptic compositions of the invention, Nausea and vomiting, abdomen caused by magnesium valprote after patient takes for a long time
Rush down, the symptoms of digestive tract such as sitophobia are slowed down, liver and renal function significantly improve.
Specific implementation mode
The following examples will make the present invention more specifically to explain, but the present invention is not limited only to these implementations
Example, these same embodiments are not also limit the invention in any way.
The raw materials and consumption (parts by weight) of the antiepileptic compositions of embodiment 1-6 is as shown in table 1：
1. embodiment 1-6 antiepileptics composition material of table and dosage (parts by weight)
Wherein, the preparation method of above-mentioned Fructus Alpinae Oxyphyllae extract is specially：Full fructus alpiniae oxyphyllae is chosen, shell is removed, is put into
10-16h is impregnated in the sodium chloride solution of 0.2-0.6wt%, taking-up drains, after grinder is fully ground, 3-5 times of weight of addition
70% ethyl alcohol, stirs evenly；Slurries are boiled by slow fire 40-60min, 200-400 mesh filter-cloth filterings；Filtrate is placed in high pressure homogenizer
In, under 10-15MPa pressure after homogeneous, 110-120 DEG C of high-temperature sterilization, dry, ultramicro grinding obtains.
The preparation method of above-mentioned antiepileptic compositions, includes the following steps：
1) major ingredient mixed processing：Magnesium valprote, N-BETA-Alanyl-L-histidine, Fructus Alpinae Oxyphyllae extract are weighed, after mixing in 20-30 DEG C,
200-300 mesh sieve is crossed, is fitted into vacuumize process in hermetic bag, 10-15 DEG C of freezen protective is spare；
2) mixing sterilizing：Weigh magnesium stearate, Brij30, antioxidant, surfactant, Lactis Anhydrous,
PVP K30 is added in the major ingredient of freezen protective, is uniformly mixed, and crosses 60-80 mesh sieve, and 80-90 DEG C of instantaneous sterilizing 3-6s is obtained
Mixture；Wherein, the steam pressure of instantaneous sterilizing is 0.5-0.7MPa, and drop temperature is less than 55 DEG C.
3) it suppresses：Using powder direct pressure closing by the tablet of the tabletted heavy 200-220mg of mixture.
Comparative example 1
It is identical as the preparation method of embodiment 3, lack the addition of Fructus Alpinae Oxyphyllae extract.
Comparative example 2
It is identical as the preparation method of embodiment 3, lack the addition of N-BETA-Alanyl-L-histidine.
Comparative example 3
It is identical as the preparation method of embodiment 3, lack the addition of Brij30.
Comparative example 4
It is identical as the preparation method of embodiment 3, lack the addition of antioxidant butyl anisole.
Comparative example 5
It is identical as the preparation method of embodiment 3, lack the addition of surface agent poloxamer.
Comparative example 6
It is identical as the preparation method of embodiment 3, lack the addition of PVP K30.
Comparative example 7
The valproic acid magnesium sheet for selecting Xiangzhong Pharmaceutical Co Ltd, Hunan Prov's production, pulverizes rear tabletted heavy 200-220mg
Tablet.
Comparative example 8
The anti-epileptic composition of embodiment 1 in the patent of reference publication No. CN105770973A, the anti-epileptic composition
It is 330 parts of Nattokinase, 100 parts of red bean rice flour, 240 parts of γ-aminobutyric acid, 400 parts of taurine, Vitamin C to be formulated (parts by weight)
400 parts of acid, 520 parts of haematococcus pluvialis, 1500 parts of blueberry powder, 1500 parts of PURE WHEY, 150 parts of dietary fiber, lutein
0.012 part；The tablet of piece weight 200mg is made after mixing of powder direct pressure closing.
Comparative example 9
The anti-epileptic composition of medicine of embodiment 3, the anti-epileptic combine medicine in the patent of reference publication No. CN104147020A
Object includes aspirin 20mg, caffeine 10mg, sodium phenobarbital 30mg, dilantin sodium 50mg, lactose 240mg, microcrystalline cellulose
Plain 110mg, carboxylic formaldehyde fibers element calcium 10mg, silicic acid anhydride 10mg, Carboxypropionyl cellulose 15mg, magnesium stearate 5mg, use are wet
Method granulation, dry, the tablet of piece weight 200mg is made in tabletting after whole grain.
Zoopery
Experimental subjects：256 adult Wistar rats, 180 ± 10g of weight are chosen, male and female have concurrently, are tested by Shandong Province dynamic
Object monitoring center provides.
Experimental method：Rat is randomly divided into 16 groups：I.e. epilepsy model group, embodiment 1-6 treatment groups, comparative example 1-9 are controlled
Treatment group, each group are 16, and the preceding ad lib under laboratory environment of experiment, drinking-water control 23 ± 8 DEG C of laboratory temperature, daytime
Night circulation light shines.Using pentylenetetrazole intraperitoneal injection modeling, injected to rat according to the standard of sub- seizure dose 32mg/kg, even
Continuous injection 30 days.Consecutive identical dosage is injected intraperitoneally 5 days again after stopping seven days, after be changed to every 3 days once abdominal cavity injections.Modeling at
After work(, according to the dosage of 0.05mg/g, rat is filled using the antiepileptic compositions of embodiment, comparative example treatment group
Stomach, once a day, continuous 3 months, epilepsy model group normal water, feeding observed and recorded the behaviouristics of each treatment group rat
Variation.The results are shown in Table 2 for influence of the antiepileptic to EEG of epileptic rats degree：
According to standard (the Racine RJ.Modification of seizure activity by of Racine
electrical stimulation：II motor seizure.Electroenceph Clin Neurophysiol, 1972,
32：281-294)：0 grade, no significant reaction；I grades, rhythmicity face is twitched；It II grades, nods or wet dog sample is shaken, scratched；III
Grade, single limb are twitched；IV grades, more limbs twitches or tetanic；V grades, generalized tonic-clonic seizure.) in table number for statistics each hair
Make the number of rats amount of rank, the adduction of 0-V grades and The dead quantity is 16, and 0 grade indicates that epilepsy is cured, and I grades of-V grades of expressions are also deposited
In different degrees of epileptic symptom.
2. antiepileptic compositions of table influence EEG of epileptic rats degree
| Group | 0 grade | I grades | II grades | III level | IV grades | V grades | It is dead |
| Model group | 0 | 0 | 0 | 3 | 5 | 3 | 5 |
| Embodiment 1 | 9 | 5 | 2 | 0 | 0 | 0 | 0 |
| Embodiment 2 | 10 | 3 | 3 | 0 | 0 | 0 | 0 |
| Embodiment 3 | 12 | 4 | 0 | 0 | 0 | 0 | 0 |
| Embodiment 4 | 10 | 4 | 2 | 0 | 0 | 0 | 0 |
| Embodiment 5 | 10 | 3 | 2 | 1 | 0 | 0 | 0 |
| Embodiment 6 | 9 | 3 | 3 | 1 | 0 | 0 | 0 |
| Comparative example 1 | 5 | 3 | 3 | 2 | 1 | 1 | 1 |
| Comparative example 2 | 4 | 5 | 2 | 1 | 1 | 1 | 2 |
| Comparative example 3 | 5 | 3 | 4 | 2 | 2 | 0 | 0 |
| Comparative example 4 | 7 | 3 | 3 | 1 | 2 | 0 | 0 |
| Comparative example 5 | 8 | 1 | 4 | 2 | 1 | 0 | 0 |
| Comparative example 6 | 6 | 3 | 3 | 2 | 2 | 0 | 0 |
| Comparative example 7 | 9 | 2 | 3 | 1 | 1 | 0 | 0 |
| Comparative example 8 | 7 | 3 | 2 | 1 | 2 | 0 | 1 |
| Comparative example 9 | 5 | 1 | 2 | 2 | 3 | 1 | 2 |
As can be seen from the above table, the antiepileptic of the embodiment of the present invention is higher to the cure rate of mouse, and embodiment 3 reaches
75% cure rate, and compared with comparative example, there is only the epileptic symptoms that slight I grades arrive III level after treatment, without dead
Die generation；Comparative example 1, comparative example 2 lack Fructus Alpinae Oxyphyllae extract, N-BETA-Alanyl-L-histidine, and the improvement of function is supplied oxygen to nerve modulation and cell
Declines, epilepsy therapy significant effect reduce, and high-level symptom exists, and also death condition occurs；Comparative example 3- comparative examples 6
It is compared than embodiment 3, due to lacking lubricant Brij30, antioxidant butyl anisole, surface-active respectively
Agent poloxamer, adhesive poloxamer are prepared rear stability in tablet, have a certain impact in curative effect, high level
Symptom occurs, but does not have death condition.Comparative example 7 uses commercially available magnesium valprote, is still not so good as the present invention in curative effect
The antiepileptic compositions of embodiment.To sum up, the epilepsy type symptom curative effect of antiepileptic compositions of the invention to rat
It is good, and safety is higher than the prior art.
Clinical treatment is tested
Treatment object：300 all kinds of epileptics of selection, wherein male 184, women 116, age 12-65 Sui, with
Machine is divided into 15 groups, embodiment 1-6 treatment groups and comparative example 1-9 treatment groups, every group 20；It is required that patient without hypertension, diabetes,
Heart disease, gastric ulcer, duodenal ulcer, gestation and to magnesium valprote, N-BETA-Alanyl-L-histidine, Fructus Alpinae Oxyphyllae extract allergy sufferers.
Therapy：The antiepileptic for being formulated and being prepared in table 1 is taken respectively by embodiment treatment group, comparative example treatment group
Compositions, each taking antiepileptic compositions 200mg, twice daily, daily maximum dose level be no more than 600mg, 3 months
1 course for the treatment of, takes 12 months；Side effect performance includes nausea,vomiting,diarrhea, sitophobia, myasthenia, trembling of limbs, drowsiness, confused
Fan, incidence of side effects statistics is the incidence situation treated first 3 months, and specific treatment results are shown in Table 3.
Curative effect determinate standard：Symptomatic condition, the side effect profile for observing and recording each course for the treatment of are sent out for first 3 months with treatment
Working frequency is control to calculate the variation of seizure trequency.It is specifically divided into following several Judging index：
It cures：Clinic remains dormant, and symptom disappears substantially；
It is effective：Seizure trequency is reduced to 25% or less；
Effectively：Seizure trequency is reduced to 25%-50%；
In vain：Seizure frequency is reduced to 50% or more；
Total effective rate=(cure+effective+effectively)/total number of cases.
3. antiepileptic compositions clinical treatment outcome of table
The treatment group that can be seen that the embodiment of the present invention by the therapeutic effect of antiepileptic compositions controls patient
More rate, total effective rate are compared with comparative example height, and the total effective rate of embodiment 3 reaches 95%, and incidence of side effects is relatively low, illustrates this hair
Bright antiepileptic compositions good effect, it is safe.Comparative example 1-6 lacks Fructus Alpinae Oxyphyllae extract, N-BETA-Alanyl-L-histidine or auxiliary material
Addition, medicine stability and curative effect are substantially reduced, and total effective rate has certain reduction；Comparative example 7 uses magnesium valprote, still deposits
In more side reaction symptom.
Model case
Case 1：Lee, male, 53 years old, ictal olfactory hallucination 50 days, apocleisis, unconsciousness broke out one time 1 for 1-2 days, breaking-out
When tic of limbs, spit out white foams, lockjaw, continue 3-4 minute after, twitch stop, about after half an hour realize gradually recovery, no
Episode process can be recalled, took Carbamazepine Tablets, epilepsy health, phenytoin sodium tablet before, broken out after drug withdrawal frequent.Take this hair
After bright antiepileptic after 2 courses for the treatment of, symptom is substantially reduced, and the side effects such as vomiting, diarrhea, digestive discomfort fade away, 3
The check of course for the treatment of Hou Qu hospitals has been cured, and appetite improves, and complexion takes a turn for the better.
Case 2：Zhang, women, 14 years old, initial representation was to be vomitted after falling asleep, and liver and renal function are poor, and when sleep goes out
Existing right side face is twitched, and then right upper extremity and right lower extremity twitch, spit out white foams, and gatism is clouded in mind, continues 30 seconds left sides
Alleviated on the right side.Slow-releasing magnesium propylvalerate tablet, Sustained-release Sodium Valproate were taken, occasionally has breaking-out after drug withdrawal, and with vomiting, abdomen
It rushes down, the side effects such as stomach angina.After 1 course for the treatment of of antiepileptic compositions for taking the present invention, symptom is just alleviated substantially, sleep
Shi Xiangtian will not occur face twitch and tic of limbs, cured substantially in hospital's check after 2 courses for the treatment of, liver and kidney
Function also take a favorable turn, be discontinued later six months after in and have epileptic attack.
Case 3：Mr. Wang, male's property 36 years old, is broken out 3-5 times weekly, when breaking-out tetany, two mesh turn over, spit out white foams,
Obnubilation is waken up after about 3-5min.Usually in case of scaring, breakfast skipping, upper sense fever then easily induce.Previous tretament is with anti-insane
It based on epilepsy Chinese medicine, does not reaccess, cures after taking three courses for the treatment of of drug of the present invention, asymptomatic appearance in half a year.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (9)
1. a kind of antiepileptic compositions, which is characterized in that include the raw material of following parts by weight：20-65 parts of magnesium valprote, L-
10-30 parts of carnosine, 5-20 parts of Fructus Alpinae Oxyphyllae extract, 3-8 parts of PVP K30,2-6 parts of magnesium stearate, Brij30
3-10 parts, 2-8 parts of antioxidant, 1-6 parts of surfactant, 60-100 parts of Lactis Anhydrous.
2. antiepileptic compositions according to claim 1, which is characterized in that the antiepileptic includes following heavy
Measure the raw material of part：32-40 parts of magnesium valprote, 16-23 parts of N-BETA-Alanyl-L-histidine, 10-15 parts of Fructus Alpinae Oxyphyllae extract, 4-6 parts of PVP K30,
3-5 parts of magnesium stearate, 5-8 parts of Brij30,4-7 parts of antioxidant, 2-4 parts of surfactant, Lactis Anhydrous 70-88
Part.
3. antiepileptic compositions according to claim 1, which is characterized in that the antioxidant is fourth hydroxyl fennel
Ether, butyl hydroxytoluene, ascorbic acid or sodium sulfite.
4. antiepileptic compositions according to claim 1, which is characterized in that the surfactant is triglyceride
Fat acid esters, fatty acid sorbitan or poloxamer.
5. antiepileptic compositions according to claim 1, which is characterized in that the preparation side of the Fructus Alpinae Oxyphyllae extract
Method is specially：Full fructus alpiniae oxyphyllae is chosen, shell is removed, is put into the sodium chloride solution of 0.2-0.6wt% and impregnates 10-16h, take
Go out to drain, after grinder is fully ground, 70% ethyl alcohol of 3-5 times of weight is added, stirs evenly；Slurries are boiled by slow fire 40-
60min, 100-200 mesh filter-cloth filtering；Filtrate is placed in high pressure homogenizer, under 10-15MPa pressure after homogeneous, 110-120 DEG C
High-temperature sterilization, dry, ultramicro grinding obtain.
6. according to the preparation method of claim 1-5 any one of them antiepileptic compositions, which is characterized in that including with
Lower step：
1) major ingredient mixed processing：Weigh magnesium valprote, N-BETA-Alanyl-L-histidine, Fructus Alpinae Oxyphyllae extract, after mixing in 20-30 DEG C, mistake
200-300 mesh sieves, and is fitted into hermetic bag, 10-15 DEG C of freezen protective is spare；
2) mixing sterilizing：Weigh magnesium stearate, Brij30, antioxidant, surfactant, Lactis Anhydrous, poly- dimension
Ketone K30, is added in the major ingredient of freezen protective, is uniformly mixed, and crosses 60-80 mesh sieve, and 80-90 DEG C of instantaneous sterilizing 3-6s is mixed
Material；
3) it suppresses：It is using powder direct pressure closing that mixture is tabletted.
7. the preparation method of antiepileptic compositions according to claim 6, which is characterized in that the step 1) is packed into
It needs to do vacuumize process after hermetic bag.
8. the preparation method of antiepileptic compositions according to claim 6, which is characterized in that the step 2) is instantaneous
The steam pressure of sterilizing is 0.5-0.7MPa, and drop temperature is less than 55 DEG C.
9. the preparation method of antiepileptic compositions according to claim 6, which is characterized in that the step 3) compacting
At tablet piece weight be 200-220mg.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810226923.7A CN108578678A (en) | 2018-03-13 | 2018-03-13 | A kind of antiepileptic compositions and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810226923.7A CN108578678A (en) | 2018-03-13 | 2018-03-13 | A kind of antiepileptic compositions and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108578678A true CN108578678A (en) | 2018-09-28 |
Family
ID=63626643
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810226923.7A Withdrawn CN108578678A (en) | 2018-03-13 | 2018-03-13 | A kind of antiepileptic compositions and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108578678A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112439049A (en) * | 2019-09-04 | 2021-03-05 | 天津诚意堂生物科技有限公司 | Specific combination formula for epilepsy |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5017613A (en) * | 1983-07-20 | 1991-05-21 | Sanofi, S. A. | Valproic acid preparations |
| CN1265889A (en) * | 1999-03-06 | 2000-09-13 | 王学勇 | Medicine for treating epilepsy |
| CN1302607A (en) * | 2000-03-24 | 2001-07-11 | 湖南省湘中制药有限公司 | Slow-releasing magnesium propylvalerate tablet and its preparing process |
| WO2003013514A1 (en) * | 2001-08-08 | 2003-02-20 | Carn-Aware Llc | Improving neurological functions |
| WO2004064866A1 (en) * | 2003-01-20 | 2004-08-05 | Innovative Vision Products, Inc. | Combined use of carnosinase inhibitor with l-carnosines and composition |
| CN101693113A (en) * | 2009-10-21 | 2010-04-14 | 严洁 | Divalproex sodium medicine composition with improved oral absorptivity |
| WO2011011376A2 (en) * | 2009-07-20 | 2011-01-27 | Biolink Life Sciences, Inc. | Methods for the preparation and use of aqueous solutions of magnesium valproate hydrate and l-carnitine |
| CN102895201A (en) * | 2011-07-26 | 2013-01-30 | 北大方正集团有限公司 | Valproate semisodium tablet and its preparation method |
| CN104146976A (en) * | 2014-08-06 | 2014-11-19 | 沈阳药科大学 | Heavy-load valproic acid drug sustained release tablet and preparation method thereof |
| CN106727386A (en) * | 2017-02-27 | 2017-05-31 | 佛山市弘泰药物研发有限公司 | A kind of divalproex sodium dispersible tablet and preparation method thereof |
-
2018
- 2018-03-13 CN CN201810226923.7A patent/CN108578678A/en not_active Withdrawn
Patent Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5017613A (en) * | 1983-07-20 | 1991-05-21 | Sanofi, S. A. | Valproic acid preparations |
| CN1265889A (en) * | 1999-03-06 | 2000-09-13 | 王学勇 | Medicine for treating epilepsy |
| CN1302607A (en) * | 2000-03-24 | 2001-07-11 | 湖南省湘中制药有限公司 | Slow-releasing magnesium propylvalerate tablet and its preparing process |
| WO2003013514A1 (en) * | 2001-08-08 | 2003-02-20 | Carn-Aware Llc | Improving neurological functions |
| WO2004064866A1 (en) * | 2003-01-20 | 2004-08-05 | Innovative Vision Products, Inc. | Combined use of carnosinase inhibitor with l-carnosines and composition |
| US20140086855A1 (en) * | 2003-01-20 | 2014-03-27 | Innovative Vision Products, Inc. | Combined use of a carnosinase inhibitor with l-carnosine or its related substance and a composition containing the same |
| WO2011011376A2 (en) * | 2009-07-20 | 2011-01-27 | Biolink Life Sciences, Inc. | Methods for the preparation and use of aqueous solutions of magnesium valproate hydrate and l-carnitine |
| CN101693113A (en) * | 2009-10-21 | 2010-04-14 | 严洁 | Divalproex sodium medicine composition with improved oral absorptivity |
| CN102895201A (en) * | 2011-07-26 | 2013-01-30 | 北大方正集团有限公司 | Valproate semisodium tablet and its preparation method |
| CN104146976A (en) * | 2014-08-06 | 2014-11-19 | 沈阳药科大学 | Heavy-load valproic acid drug sustained release tablet and preparation method thereof |
| CN106727386A (en) * | 2017-02-27 | 2017-05-31 | 佛山市弘泰药物研发有限公司 | A kind of divalproex sodium dispersible tablet and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| MARINA YAZIGI SOLIS等: "Effects of Beta-Alanine Supplementation on Brain Homocarnosine/Carnosine Signal and Cognitive Function: An Exploratory Study", 《PLOS ONE》 * |
| 李裕倩等: "益智仁乙醇提取物对东莨菪碱痴呆小鼠学习记忆的影响", 《首都师范大学学报(自然科学版)》 * |
| 陈孝治等: "《药物处方手册 第2版》", 30 June 2012, 长沙：湖南科学技术出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112439049A (en) * | 2019-09-04 | 2021-03-05 | 天津诚意堂生物科技有限公司 | Specific combination formula for epilepsy |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103054044B (en) | Sleep-improving health food composition | |
| CN104740412B (en) | A kind of Medicament for Alcoholism composition and preparation method thereof | |
| CN109432195B (en) | Extraction method and application of theanine and gamma-aminobutyric acid | |
| CN101822704A (en) | Drug combination for removing freckles and preparation method thereof | |
| CN103356807A (en) | Drug composite with function of enhancing immunity and preparation method thereof | |
| KR102138348B1 (en) | Composition comprising for preventing or treating epilepsy and Manufacturing method thereof | |
| CN103355655A (en) | Composition with alimentary anemia improving function and preparation method of composition | |
| CN103446525A (en) | Traditional Chinese medicine composition for treating skin diseases as well as preparation method and application of traditional Chinese medicine composition | |
| CN101647951B (en) | Traditional Chinese medicine composition and preparation method and application thereof | |
| CN103142916B (en) | Medicament for preventing and treating senile dementia and preparation method thereof | |
| CN108578678A (en) | A kind of antiepileptic compositions and preparation method thereof | |
| CN106729123A (en) | A kind of composition of three high drop and preparation method thereof | |
| CN103520405A (en) | Pure Chinese medicinal health preservation preparation with effects of clearing heat, nourishing yin, moistening dryness, reinforcing qi, nourishing blood and relaxing bowels | |
| CN110772564A (en) | Traditional Chinese medicine extract composition with depression mood regulating effect, preparation method thereof and traditional Chinese medicine preparation | |
| CN105101817B (en) | Edible composition and preparation method thereof and the food comprising said composition | |
| CN100350954C (en) | Chinese medicine preparation for promoting lead-removal and its preparation process | |
| CN105832877B (en) | A kind of health care product and its preparation method and application with liver-protecting efficacy | |
| CN105767718A (en) | Composition with function of dispelling chloasma and preparation method of composition | |
| CN103610795A (en) | Method for preparing eucommia ulmoides step-down oral preparation | |
| CN103933538A (en) | Medicine for treating spleen-kidney yang deficiency type cirrhosis ascites and preparation method thereof | |
| CN107213197A (en) | A kind of Chinese medicine composition and its application in prevention or treatment hypertension drug is prepared | |
| CN114098085A (en) | Functional food composition with auxiliary memory improving function and application | |
| CN105535587A (en) | Traditional Chinese medicinal preparation for treating heart and kidney disharmony type palpitation and insomnia and preparation method of traditional Chinese medicinal preparation | |
| CN104689151A (en) | Traditional Chinese medicine composition for treating diabetes and use of composition | |
| CN108938718A (en) | A kind of preparation method of Chinese medicine composition and its preparation for treating headstroke |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20180928 |
|
| WW01 | Invention patent application withdrawn after publication |