CN108542879A - A kind of injection Citicolini pharmaceutical composition and its preparation method and application - Google Patents
A kind of injection Citicolini pharmaceutical composition and its preparation method and application Download PDFInfo
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Abstract
Present invention relates particularly to a kind of injection Citicolinis and its preparation method and application.Injection Citicolini supplementary material provided by the invention includes：Citicoline, activated carbon, Chinese medical extract and water for injection；The preparation method of injection Citicolini is as follows：(1) prepare and weigh various supplementary materials by prescription；(2) first add suitable water for injection into dense preparing tank, then be sequentially added into corresponding supplementary material and stir, wait for that it is completely dissolved, activated carbon is added and simultaneously stirs, is filtered after the completion of stirring, obtains concentrated wiring liquid；(3) it send to dilute preparing tank, then water for injection is added inward to full dose, return stirring；Ph values are then adjusted, configuration amount is finally injected water to；(4) above-mentioned liquid is detected, filling and sterilizing.Function and the disturbance of consciousness caused by obstacle and other central nervous system acute injuries of the injection made from preparation method of the present invention to hemiplegia and four limbs function caused by headstroke have good therapeutic effect.
Description
Technical field
The present invention relates to biomedicine technical fields, and in particular to a kind of injection Citicolini pharmaceutical composition, its
Preparation method and application.
Background technology
Data show, by the end of the year 2016, China 60 years old and the above elderly population are more than 2.3 hundred million, account for total population
16.7%；65 years old and the above elderly population are more than 1.5 hundred million, account for the 10.8% of total population.Expect the year two thousand fifty, Aged in China population
Be up to 4.8 hundred million, account for about 2/5ths of the Asia elderly population at that time, a quarter of global elderly population, than it is now beautiful,
Three English, moral countries population's summations are more, and above-mentioned data show that China enters aging society in advance, to the elderly's
It takes care of, the elderly's excessively upper happy old age is allowed to become one important topic of Chinese society.
The problem of most critical wherein is become for the treatment of the elderly, because the elderly is with the increase at age, body machine
It also can gradually fail, be easy to suffer from various disease image height blood pressures, diabetes, heart disease chronic diseases；And with diet knot
The variation of structure, more than the elderly, present more and more young men suffer from the various diseases such as hyperglycemia, hyperlipidemia, fatty liver, these
Disease is other than their own damages human body health, it is often more important that, the complication that they cause, some meetings cause
Apoplexy, some meetings cause internal organs impaired, and some meetings cause serious injury to the nervous system of human body, these all seriously affect people
Quality of life, cause heavy financial burden to personal, family and society, seriously affected happy family life and social harmony.
Meanwhile the elderly, because older, action is more slow, and body reaction and the coordination ability are also poor, reacts meeting
It is slower than young man, it is easy to fall down, be easy to cause various tumble injuries and damage, wherein head the most serious is wounded, can cause
The acute injury of cranium brain, gently then can cerebral concussion, cause consciousness behavior disorder, heavy then craniocerebral injury can be caused, threat to life to treat
It is hard to work that craniocerebral injury relies solely on drug sometimes, generally requires to carry out operative treatment, and performing the operation has prodigious technology hardly possible
Degree, easily causes postoperative sequelae, wherein the relatively conventional consciousness for thering is nervous centralis acute injury to cause and limbs behavior
Obstacle；Currently, consciousness and physical handicaps and medicine that nervous centralis acute injury caused by performing the operation for this respect causes
It is also less, and citicoline is the obstacle side of nervous centralis acute injury causes after current iatrotechnics consciousness and limbs behavior
One of the key agents in face, there is a preferable therapeutic effect, but the preparation of citicoline drug at present, mainly with Western medicine preparation
Based on, the pharmaceutical preparation that less Combined with Chinese Herbal uses, which has limited the further performances of the raising of its curative effect and effect.
Invention content
For currently, clinically still having above-mentioned problem, present invention aims at provide a kind of citicoline note
Penetrate liquid and its preparation method and application.
The present invention is used in combination by the way that Chinese medicine is carried out Chinese and Western medicine with citicoline, is made chinese-western medicine preparation, can be helped
In the therapeutic effect for further increasing drug, contribute to limbs work(caused by the nervous centralis acute injury such as hemiplegia and operations on cranium and brain
The recovery of energy sexual dysfunction and cognitive disorder patient, the present invention are combined by Chinese and Western medicine, can play the synergistic effect of the two,
Enhance therapeutic effect, patient is contributed to faster to restore.
In order to realize that above-mentioned target, the present invention are achieved by the following technical programs：
A kind of injection Citicolini pharmaceutical composition, in terms of parts by weight including 45~150 parts of citicoline,
0.2~0.5 part of activated carbon, 5~15 parts of Chinese medical extracts and 850~950 parts of waters for injection.
Preferably, the injection Citicolini, in terms of parts by weight including 50~130 parts of citicoline,
0.25~0.45 part of activated carbon, 7~12 parts of Chinese medical extracts and 870~920 parts of waters for injection.
Preferably, the Chinese medical extract includes 15~35 parts of Notogineng Extracts, 25~40 parts of spirits in terms of parts by weight
Sesame extract and 25~45 parts of Rhizoma Gastrodiae extracts.
It is highly preferred that the Chinese medical extract, in terms of parts by weight comprising 20~35 parts of Notogineng Extracts, 25~35 parts
Ganodenna Lucidum P.E and 30~45 parts of Rhizoma Gastrodiae extracts.
Preferably, the Notogineng Extract is prepared by the following method：Radix Notoginseng is weighed, is carried with 50%~80% alcohol reflux
It takes 3~6 times, filtrate was collected by filtration in 0.5~2 hour extraction time, and filtrate recycling ethanol concentrates, obtains Radix Notoginseng after drying and crushing
Extract；The Ganodenna Lucidum P.E is prepared by the following method：Ganoderma lucidum is taken, inward the water of 15~50 times of amounts of addition, extraction 5~
12 hours, 50~75 DEG C of Extracting temperature, refluxing extraction 2~5 times；Filtrate is filtered off, concentration, drying and crushing obtain ganoderma lucidum extraction
Object；Rhizoma Gastrodiae is taken, Rhizoma Gastrodiae is crushed, refluxing extraction is carried out 2~6 times with absolute ethyl alcohol, 45~75 DEG C of Extracting temperature, when extraction
Between 3~8 hours, filter to take filtrate, filtrate extracted with petroleum ether, phase of fetching water, then concentrated, be dried to obtain Rhizoma Gastrodiae and carry
Take object.
It is highly preferred that the Notogineng Extract is prepared by the following method：Radix Notoginseng is weighed, 4 are extracted with 65% alcohol reflux
Secondary, filtrate was collected by filtration in 1 hour extraction time, and filtrate recycling ethanol concentrates, obtains Notogineng Extract after drying and crushing；It is described
Ganodenna Lucidum P.E prepare by the following method：Ganoderma lucidum is taken, the water of 35 times of amounts is added inward, is extracted 6 hours, Extracting temperature 65
DEG C, refluxing extraction 3 times；Filtrate is filtered off, concentration, drying and crushing obtain Ganodenna Lucidum P.E；Rhizoma Gastrodiae is taken, Rhizoma Gastrodiae is crushed,
Refluxing extraction is carried out with absolute ethyl alcohol 3 times, and 60 DEG C of Extracting temperature, filters to take filtrate at 5 hours extraction times, with petroleum ether to filter
Liquid is extracted, phase of fetching water, then is concentrated, is dried to obtain Rhizoma Gastrodiae extract.
Preferably, the specification of the injection Citicolini is 2ml：0.1g and 2ml：0.25g, packing specification are
2ml × 6/box × 160 boxes/case.
Preferably, the preparation method of the injection Citicolini pharmaceutical composition, comprises the steps of：
S1. prepare and weigh various raw materials by prescription and prepare ampoule needed for liquid drug；
S2. drug solution preparing is carried out, the water for injection of total configuration volume 40%~60% is added into dense preparing tank, prescription is added
Citicoline is measured, is stirred while adding 3~8 minutes, until whole dissolvings；
S3. Radix Notoginseng, ganoderma lucidum and Rhizoma Gastrodiae extract then, then is inward added, after stirring is completely dissolved to Chinese medical extract, then
The activated carbon of recipe quantity is added, stirring and adsorbing 5~15 minutes is filtered through 0.8um studs filter and 0.45um filters to dilute
Distribution tank；
S4. water for injection is added by several times to dense preparing tank, dilute preparing tank is injected by delivery pump.Benefit adds to the full amount of water for injection,
It is finally stirred at reflux 7~15 minutes.It opens cooling and is water-cooled to fluid temperature at 25~50 DEG C, regulating liquid medicine pH value makes its holding
Between 5.0~9.0；
S5. then, after above-mentioned liquid being filtered by 0.22 μm of bacterial filter, filling, filling speed 300~450 is carried out
Branch/point, filling loading amount is 2.00~2.25ml/ branch, and entire pouring process control is completed in 10 hours, is needed toward ampoule when filling
The nitrogen being inside filled with, protects liquid；
S6. canned semi-finished product are sterilized, sterilizing parameter：Steam pressure >=0.3MPa, compressed air pressure >=
0.4MPa；Embedding terminates to sterilization process to must not exceed 3 hours；
S7. it after the completion of sterilizing, then is hunted leak to semi-finished product, lamp inspection, labeling and packaging.
It is highly preferred that the preparation method of the injection Citicolini, which is characterized in that comprise the steps of：S1.
By place
Side prepares and weighs various raw materials and prepares ampoule needed for liquid drug；
S2. drug solution preparing is carried out, the water for injection of total configuration volume 45%~55% is added into dense preparing tank, prescription is added
Citicoline is measured, is stirred while adding 4~7 minutes, until whole dissolvings；
S3. Radix Notoginseng, ganoderma lucidum and Rhizoma Gastrodiae extract then, then is inward added, after stirring is completely dissolved to Chinese medical extract, then
The activated carbon of recipe quantity is added, stirring and adsorbing 7~12 minutes is filtered through 0.8um studs filter and 0.45um filters to dilute
Distribution tank；
S4. water for injection is added by several times to dense preparing tank, dilute preparing tank is injected by delivery pump.Benefit adds to the full amount of water for injection,
It is finally stirred at reflux 8~12 minutes.It opens cooling and is water-cooled to fluid temperature at 30~40 DEG C, regulating liquid medicine pH value makes its holding
Between 5.0~9.0；
S5. then, after above-mentioned liquid being filtered by 0.22 μm of bacterial filter, filling, filling speed 350~450 is carried out
Branch/point, filling loading amount is 2.05~2.20ml/ branch, and entire pouring process control is completed in 10 hours, is needed toward ampoule when filling
The nitrogen being inside filled with, protects liquid；
S6. canned semi-finished product are sterilized, sterilizing parameter：Steam pressure >=0.3MPa, compressed air pressure >=
0.4MPa；Embedding terminates to sterilization process to must not exceed 3 hours；
S7. it after the completion of sterilizing, then is hunted leak to semi-finished product, lamp inspection, labeling and packaging.
Preferably, the filling quality requirement of the liquid is：Liquid is nothing in colourless or faint yellow clear liquid, liquid
The content of citicoline should be the 90.0%~110.0% of labelled amount in naked eyes visible foreign matters and liquid.
Preferably, disturbance of consciousness medicine of the citicoline after preparing Acute Brain Injury and cerebral operations
Application in object.
Preferably, limbs disturbance of the citicoline caused by preparing headstroke and other central nervous systems
Application in the function and disturbance of consciousness medicine caused by acute injury of uniting.
Description of the drawings
Fig. 1 is the schematic process flow diagram of the present invention.
Specific implementation mode
The present invention is further elaborated with reference to specific embodiment, the embodiment is served only for explaining this hair
It is bright, it is not intended to limit the scope of the present invention.Test method used in following embodiments is routine unless otherwise specified
Method；Used material, reagent etc., unless otherwise specified, for the reagent and material commercially obtained.
Embodiment 1
A kind of injection Citicolini, in terms of parts by weight including 50 parts of citicoline, 0.25 part of activated carbon, 5 parts
Chinese medical extract and 950 parts of waters for injection.
A kind of preparation method of injection Citicolini, comprises the steps of：
S1. prepare and weigh various raw materials by prescription and prepare ampoule needed for liquid drug；
S2. drug solution preparing is carried out, the water for injection of total configuration volume 40% is added into dense preparing tank, recipe quantity born of the same parents two are added
Phosphorus choline stirs while adding 3 minutes, until whole dissolvings；
S3. Radix Notoginseng, ganoderma lucidum and Rhizoma Gastrodiae extract then, then is inward added, after stirring is completely dissolved to Chinese medical extract, then
Be added recipe quantity 0.25 part of activated carbon, stirring and adsorbing 5 minutes, through 0.8um studs filter and 0.45um filters filter to
Dilute preparing tank；
S4. water for injection is added by several times to dense preparing tank, dilute preparing tank is injected by delivery pump.Benefit adds to the full amount of water for injection,
It is finally stirred at reflux 7~15 minutes.It opens cooling and is water-cooled to fluid temperature at 30 DEG C, regulating liquid medicine pH value is kept it in
5.2；
S5. then, after above-mentioned liquid being filtered by 0.22 μm of bacterial filter, filling, 330/point of filling speed is carried out,
Filling loading amount is 2.05ml/ branch, and entire pouring process control is completed in 10 hours, and the nitrogen being filled in ampoule is needed when filling
Gas protects liquid；
S6. canned semi-finished product are sterilized, sterilizing parameter：Steam pressure >=0.3MPa, compressed air pressure >=
0.4MPa；Embedding terminates to sterilization process to must not exceed 3 hours；
S7. it after the completion of sterilizing, then is hunted leak to semi-finished product, lamp inspection, labeling and packaging.
Embodiment 2
A kind of injection Citicolini, including 135 parts of citicoline, 0.45 part of activated carbon, 13 in terms of parts by weight
Part Chinese medical extract and 850 parts of waters for injection.
A kind of preparation method of injection Citicolini, comprises the steps of：
S1. prepare and weigh various raw materials by prescription and prepare ampoule needed for liquid drug；
S2. drug solution preparing is carried out, the water for injection of total configuration volume 60% is added into dense preparing tank, recipe quantity born of the same parents two are added
Phosphorus choline stirs while adding 7 minutes, until whole dissolvings；
S3. Radix Notoginseng, ganoderma lucidum and Rhizoma Gastrodiae extract then, then is inward added, after stirring is completely dissolved to Chinese medical extract, then
Be added recipe quantity 0.45 part of activated carbon, stirring and adsorbing 13 minutes, through 0.8um studs filter and 0.45um filters filter to
Dilute preparing tank；
S4. water for injection is added by several times to dense preparing tank, dilute preparing tank is injected by delivery pump.Benefit adds to the full amount of water for injection,
It is finally stirred at reflux 7~15 minutes.It opens cooling and is water-cooled to fluid temperature at 48 DEG C, regulating liquid medicine pH value is kept it in
Between 8.5；
S5. then, after above-mentioned liquid being filtered by 0.22 μm of bacterial filter, filling, 420/point of filling speed is carried out,
Filling loading amount is 2.20ml/ branch, and entire pouring process control is completed in 10 hours, and the nitrogen being filled in ampoule is needed when filling
Gas protects liquid；
S6. canned semi-finished product are sterilized, sterilizing parameter：Steam pressure >=0.3MPa, compressed air pressure >=
0.4MPa；Embedding terminates to sterilization process to must not exceed 3 hours；
S7. it after the completion of sterilizing, then is hunted leak to semi-finished product, lamp inspection, labeling and packaging.
Embodiment 3
A kind of injection Citicolini, which is characterized in that in terms of parts by weight including 90 parts of citicoline, 0.35 part
Activated carbon, 10 parts of Chinese medical extracts and 900 parts of waters for injection.
S1. prepare and weigh various raw materials by prescription and prepare ampoule needed for liquid drug；
S2. drug solution preparing is carried out, the water for injection of total configuration volume 50% is added into dense preparing tank, recipe quantity born of the same parents two are added
Phosphorus choline stirs while adding 5 minutes, until whole dissolvings；
S3. Radix Notoginseng, ganoderma lucidum and Rhizoma Gastrodiae extract then, then is inward added, after stirring is completely dissolved to Chinese medical extract, then
0.35 part of the activated carbon of recipe quantity, stirring and adsorbing 5~15 minutes, through 0.8um studs filter and 0.45um filter mistakes is added
It filters to dilute preparing tank；
S4. water for injection is added by several times to dense preparing tank, dilute preparing tank is injected by delivery pump.Benefit adds to the full amount of water for injection,
It is finally stirred at reflux 7~15 minutes.It opens cooling and is water-cooled to fluid temperature at 25~50 DEG C, regulating liquid medicine pH value makes its holding
Between 5.0~9.0；
S5. then, after above-mentioned liquid being filtered by 0.22 μm of bacterial filter, filling, filling speed 300~450 is carried out
Branch/point, filling loading amount is 2.00~2.25ml/ branch, and entire pouring process control is completed in 10 hours, is needed toward ampoule when filling
The nitrogen being inside filled with, protects liquid；
S6. canned semi-finished product are sterilized, sterilizing parameter：Steam pressure >=0.3MPa, compressed air pressure >=
0.4MPa；Embedding terminates to sterilization process to must not exceed 3 hours；
S7. it after the completion of sterilizing, then is hunted leak to semi-finished product, lamp inspection, labeling and packaging.
1. influence of the injection Citicolini to Reperfusion Injury of Spinal Cord
Health and the roughly the same small white mouse 50, weight 200g or so of growing state, are randomly divided into 5 groups, and control group lacks
Blood reperfusion injury group, the advance administration group of injection Citicolini of the present embodiment, (the commercially available other born of the same parents two of positive controls 1
The advance administration group of phosphorus choline drug) and positive controls 2 (commercially available other injured nerves resume treatment the advance administration group of drug), respectively
Group is all made of improvement Zivin methods and establishes Reperfusion Injury of Spinal Cord model, and 12,24,48 and 72 hours after perfusion 4
Time point is moved to Spinal Cord of Mouse using improvement Tarlov methods and sensory function carries out scoring comparison, control group and Ischemia Reperfusion
Noting damage group, daily early morning used physiological saline 2ml gavages, the injection Citicolini of the present embodiment advance respectively in preoperative 3 days
Administration group, positive controls 1 (commercially available other advance administration groups of citicoline drug) and positive controls 2 (it is commercially available it is other by
Damage the advance administration group of nerve recovery medicine) use the citicoline of 0.4g/kg the present embodiment to inject respectively in the same period
Liquid, commercially available other citicoline drugs and commercially available other nerve recovery medicine normal saline dilutions are to 2ml gavage (phases
The results are shown in Table 1 for pass).
Reference literature simultaneously establishes spinal cord ischemia/reperfusion model in conjunction with Zivin improved methods.So preoperative animal
Fasting 8h.Using 10% chloraldurate through 0.4ml/100g anesthesia is injected intraperitoneally.After rat dorsal position is fixed, depilatory solution abdomen is normal
It is sterilized after rule depilation, then splits abdominal cavity along hunter's line, encase intestinal tube with warm saline gauze gently touches to the left, detaches and exposes
Go out abdominal aorta, carefully recognizes bilateral renal arteries.The right infrarenal aorta threading of control group, does not ligature；Two phosphorus of born of the same parents of the present embodiment
2 groups of the advance administration group of choline injection, positive controls 1 and positive controls are pressed from both sides between the arteria renalis of left and right with noninvasive artery clamp
Abdominal aorta is closed, disappear in the following abdominal pulse of clamp point and observes that hind leg cyanosis starts timing.It is unclamped after 45min dynamic
Arteries and veins presss from both sides promoting circulation of blood perfusion.It is not damaged and intraperitoneal whether there is or not abdominal cavity is closed after bleeding to check that artery has, wound applies erythromycin ointment outside.
Maintain anus temperature at 36~38 DEG C with heat lamp in art.
Each group is can be seen that from the data of table 1 to be compared with control group reference, the small white mouse limbs work(of the present embodiment group
Energy highest scoring, hence it is evident that be higher than other each groups, this shows that the injection of the present embodiment damages Spinal Cord of Mouse ischemia-reperfusion
The recovery capability of limbs disturbance caused by wound is most strong, and the limb function for being better than positive controls 1 and positive controls 2 restores
Effect, this shows exclusive use by the way that citicoline and Chinese medicine preparation combined effect to be better than to citicoline and commercially available
Some other injured nerve functional treatments drug, citicoline is combined with Chinese medicine preparation can enhance Spinal Cord of Mouse
The recovery capability and therapeutic effect of limbs disturbance caused by impaired.
Small white mouse limb function is influenced after 1 each group Reperfu- sion of table
a：P<0.01, compared with the control group；b：P<0.05, compared with ischemical reperfusion injury group
2.TUNEL detects positive apoptosis cells expression
Health and the roughly the same small white mouse 50, weight 200g or so of growing state, are randomly divided into 5 groups, and control group lacks
Blood reperfusion injury group, the advance administration group of injection Citicolini of the present embodiment, (the commercially available other born of the same parents two of positive controls 1
The advance administration group of phosphorus choline drug) and positive controls 2 (commercially available other injured nerves resume treatment the advance administration group of drug), respectively
Group is all made of improvement Zivin methods and establishes Reperfusion Injury of Spinal Cord model, and 12,24,48 and 72 hours after perfusion 4
Time point is moved to Spinal Cord of Mouse using improvement Tarlov methods and sensory function carries out scoring comparison, control group and Ischemia Reperfusion
Noting damage group, daily early morning used physiological saline 2ml gavages, the injection Citicolini of the present embodiment advance respectively in preoperative 3 days
Administration group, positive controls 1 (commercially available other advance administration groups of citicoline drug) and positive controls 2 (it is commercially available it is other by
Damage the advance administration group of nerve recovery medicine) use the citicoline of 0.4g/kg the present embodiment to inject respectively in the same period
Liquid, commercially available other citicoline drugs and commercially available other nerve recovery medicine normal saline dilutions are to 2ml gavage (phases
The results are shown in Table 2 for pass).
2 each timing node TUNEL positive cells of table expression statistics
a：P<0.01, compared with the control group；b：P<0.05, compared with ischemical reperfusion injury group
TUNEL results are as shown in 2 data of table, compared with the control group, ischemical reperfusion injury group, the present embodiment two phosphorus of born of the same parents
The advance administration group of choline injection, positive controls 1 (commercially available other advance administration groups of citicoline drug) and positive control
Positive apoptotic cells number showed increased can be observed in 2 (commercially available other injured nerves resume treatment the advance administration group of drug) of group；
Compared with ischemical reperfusion injury group, the advance administration group of injection Citicolini, positive controls 1 and the positive of the present embodiment
2 each time point apoptosis cell of control group is reduced, but the positive cell of the present embodiment injection group reduces minimum number, hence it is evident that
Less than other each groups, show that it is most strong to the protective effect of positive cell, it is stronger to more other groups of the inhibiting effect of its reduction.
3. immunohistochemistry detects Bax, Caspase-9 and Bcl-2
Health and the roughly the same small white mouse 40, weight 200g or so of growing state, are randomly divided into 8 groups, and control group lacks
Blood reperfusion injury group, the advance administration group of injection Citicolini of the present embodiment, (the commercially available other born of the same parents two of positive controls 1
The advance administration group of phosphorus choline drug) and positive controls 2 (commercially available other injured nerves resume treatment the advance administration group of drug), respectively
Group is all made of improvement Zivin methods and establishes Reperfusion Injury of Spinal Cord model, and 12,24,48 and 72 hours after perfusion 4
Time point is moved to Spinal Cord of Mouse using improvement Tarlov methods and sensory function carries out scoring comparison, control group and Ischemia Reperfusion
Noting damage group, daily early morning used physiological saline 2ml gavages, the injection Citicolini of the present embodiment advance respectively in preoperative 3 days
Administration group, positive controls 1 (commercially available other advance administration groups of citicoline drug) and positive controls 2 (it is commercially available it is other by
Damage the advance administration group of nerve recovery medicine) use the citicoline of 0.4g/kg the present embodiment to inject respectively in the same period
Liquid, commercially available other citicoline drugs and commercially available other nerve recovery medicine normal saline dilutions are to 2ml gavage (phases
The results are shown in Table 3 for pass).
3 each group Bax, Caspase-9 and Bcl-2 immunohistochemistry positive cell situation of change of table
a：P<0.01, compared with the control group；b：P<0.01, compared with ischemical reperfusion injury group
After Reperfusion Injury of Spinal Cord, Bcl-2 and bax expression increase, this is consistent with related research.Bcl-2 and bax
The ratio of the two can reflect that the apoptosis trend of cell, Bax/Bcl-2 ratios increase to a certain extent, promote the generation of apoptosis,
And Bcl-2/Bax ratios increase, and inhibit Apoptosis.After Reperfusion Injury of Spinal Cord, Bcl-2 and the apparent increasing of Bax expression
Add, prompt Reperfusion Injury of Spinal Cord with the presence of a large amount of Apoptosis, but the reduction of Bcl-2/Bax ratios, nerve cell is to withering
The direction progress died.And Bcl-2 can prevent mitochondria penetrability transhipment hole from opening, and be risen in the generation for inhibiting Apoptosis important
Effect；Correlative study is also shown, and activates caspase systems, caspase is made to increase, and can promote spinal cord neural cell that apoptosis occurs；
As can be seen from Table 3, compared with the control group, Bax, Caspase-9 and Bcl-2 immunohistochemistry positive cell variation of each group
In situation, the Bcl-2 in the present embodiment injection group increases most, Bax/Bcl-2 minimums, and Caspase-9 accelerates also most
It is few；This shows that it plays the role of stronger inhibition nerve cell apoptosis relative to positive controls 1 and positive controls 2, inhibits
Effect is preferably also, and shows that better effect can be played for inhibition nerve cell apoptosis by chinese-western medicine preparation combination.
Finally it should be noted that the above embodiments are merely illustrative of the technical solutions of the present invention, rather than the present invention is protected
The limitation of range is protected, although being explained in detail to the present invention with reference to preferred embodiment, those skilled in the art answer
Work as understanding, technical scheme of the present invention can be modified or replaced equivalently, without departing from the reality of technical solution of the present invention
Matter and range.
Claims (9)
1. a kind of injection Citicolini pharmaceutical composition, which is characterized in that including 45~150 parts of born of the same parents two in terms of parts by weight
Phosphorus choline, 0.2~0.5 part of activated carbon, 5~15 parts of Chinese medical extracts and 850~950 parts of waters for injection.
2. injection Citicolini pharmaceutical composition according to claim 1, which is characterized in that the traditional Chinese medicine extraction
Object is in terms of parts by weight, including 15~35 parts of Notogineng Extracts, 25~40 parts of Ganodenna Lucidum P.Es and 25~45 parts of Rhizoma Gastrodiae extracts.
3. Chinese medical extract according to claim 2, which is characterized in that the Notogineng Extract is made by the following method
It is standby：Radix Notoginseng is weighed, is extracted 3~6 times with 50%~80% alcohol reflux, filtrate was collected by filtration in 0.5~2 hour extraction time, filter
Liquid recycles ethyl alcohol, and Notogineng Extract is obtained after concentration, drying and crushing；The Ganodenna Lucidum P.E is prepared by the following method：It takes
The water of 15~50 times of amounts is added in ganoderma lucidum inward, extracts 5~12 hours, 50~75 DEG C of Extracting temperature, refluxing extraction 2~5 times；It crosses
Filtrate is filtered off, concentration, drying and crushing obtain Ganodenna Lucidum P.E；Rhizoma Gastrodiae is taken, Rhizoma Gastrodiae is crushed, is flowed back with absolute ethyl alcohol
Extraction 2~6 times, 45~75 DEG C of Extracting temperature, filters to take filtrate at 3~8 hours extraction times, is extracted to filtrate with petroleum ether
It takes, phase of fetching water, then is concentrated, is dried to obtain Rhizoma Gastrodiae extract.
4. injection Citicolini according to claim 1, which is characterized in that the injection Citicolini
Specification is 2ml：0.1g and 2ml：0.25g, packing specification are 2ml × 6/box × 160 boxes/case.
5. a kind of preparation method of injection Citicolini pharmaceutical composition described in claim 1, which is characterized in that include
Following steps：
S1. prepare and weigh various raw materials by prescription and prepare ampoule needed for liquid drug；
S2. drug solution preparing is carried out, the water for injection of total configuration volume 40%~60% is added into dense preparing tank, recipe quantity born of the same parents are added
Two phosphorus choline stir while adding 3~8 minutes, until whole dissolvings；
S3. Radix Notoginseng, ganoderma lucidum and Rhizoma Gastrodiae extract then, then inward is added to add after stirring is completely dissolved to Chinese medical extract
The activated carbon of recipe quantity, stirring and adsorbing 5~15 minutes, is filtered through 0.8um studs filter and 0.45um filters to dilute preparing tank；
S4. water for injection is added by several times to dense preparing tank, dilute preparing tank is injected by delivery pump.Benefit adds to the full amount of water for injection, finally
It is stirred at reflux 7~15 minutes.It opens cooling and is water-cooled to fluid temperature at 25~50 DEG C, regulating liquid medicine pH value is kept it in
Between 5.0~9.0；
S5. then, after above-mentioned liquid being filtered by 0.22 μm of bacterial filter, progress is filling, and filling speed 300~450/
Point, filling loading amount is 2.00~2.25ml/ branch, and entire pouring process control is completed in 10 hours, is needed in ampoule when filling
The nitrogen being filled with, protects liquid；
S6. canned semi-finished product are sterilized, sterilizing parameter：Steam pressure >=0.3MPa, compressed air pressure >=
0.4MPa；Embedding terminates to sterilization process to must not exceed 3 hours；
S7. it after the completion of sterilizing, then is hunted leak to semi-finished product, lamp inspection, labeling and packaging.
6. the preparation method of injection Citicolini according to claim 5, which is characterized in that comprise the steps of：
S1. prepare and weigh various raw materials by prescription and prepare ampoule needed for liquid drug；
S2. drug solution preparing is carried out, the water for injection of total configuration volume 45%~55% is added into dense preparing tank, recipe quantity born of the same parents are added
Two phosphorus choline stir while adding 4~7 minutes, until whole dissolvings；
S3. Radix Notoginseng, ganoderma lucidum and Rhizoma Gastrodiae extract then, then inward is added to add after stirring is completely dissolved to Chinese medical extract
The activated carbon of recipe quantity, stirring and adsorbing 7~12 minutes, is filtered through 0.8um studs filter and 0.45um filters to dilute preparing tank；
S4. water for injection is added by several times to dense preparing tank, dilute preparing tank is injected by delivery pump.Benefit adds to the full amount of water for injection, finally
It is stirred at reflux 8~12 minutes.It opens cooling and is water-cooled to fluid temperature at 30~40 DEG C, regulating liquid medicine pH value is kept it in
Between 5.0~9.0；
S5. then, after above-mentioned liquid being filtered by 0.22 μm of bacterial filter, progress is filling, and filling speed 350~450/
Point, filling loading amount is 2.05~2.20ml/ branch, and entire pouring process control is completed in 10 hours, is needed in ampoule when filling
The nitrogen being filled with, protects liquid；
S6. canned semi-finished product are sterilized, sterilizing parameter：Steam pressure >=0.3MPa, compressed air pressure >=
0.4MPa；Embedding terminates to sterilization process to must not exceed 3 hours；
S7. it after the completion of sterilizing, then is hunted leak to semi-finished product, lamp inspection, labeling and packaging.
7. the preparation method of injection Citicolini pharmaceutical composition according to claim 4, which is characterized in that described
The filling quality requirement of liquid be：Liquid is to be visible by naked eyes foreign matter and liquid in colourless or faint yellow clear liquid, liquid
The content of middle citicoline should be the 90.0%~110.0% of labelled amount.
8. the disturbance of consciousness of the citicoline according to claim 1 after preparing Acute Brain Injury and cerebral operations is controlled
Treat the application in drug.
9. limbs disturbance of the citicoline according to claim 1 caused by preparing headstroke and other maincenters god
Through the application in function and disturbance of consciousness medicine caused by system acute injury.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810629940.5A CN108542879A (en) | 2018-06-19 | 2018-06-19 | A kind of injection Citicolini pharmaceutical composition and its preparation method and application |
| PH12018050518A PH12018050518A1 (en) | 2018-06-19 | 2018-11-27 | Citicoline Pharmaceutical Composition For Injection, Its Preparation Method And Application Thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810629940.5A CN108542879A (en) | 2018-06-19 | 2018-06-19 | A kind of injection Citicolini pharmaceutical composition and its preparation method and application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108542879A true CN108542879A (en) | 2018-09-18 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201810629940.5A Pending CN108542879A (en) | 2018-06-19 | 2018-06-19 | A kind of injection Citicolini pharmaceutical composition and its preparation method and application |
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| Country | Link |
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| CN (1) | CN108542879A (en) |
| PH (1) | PH12018050518A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113244324A (en) * | 2021-03-04 | 2021-08-13 | 南京焰帆生物技术有限公司 | Citicoline combined medicine and preparation method and application thereof |
| CN114955031A (en) * | 2022-05-27 | 2022-08-30 | 山东希尔康泰药业有限公司 | Diclofenac sodium lidocaine hydrochloride injection aseptic preparation system |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1226439A (en) * | 1998-11-20 | 1999-08-25 | 李国荣 | Composite medicinal injection for hemiparalysis |
-
2018
- 2018-06-19 CN CN201810629940.5A patent/CN108542879A/en active Pending
- 2018-11-27 PH PH12018050518A patent/PH12018050518A1/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1226439A (en) * | 1998-11-20 | 1999-08-25 | 李国荣 | Composite medicinal injection for hemiparalysis |
Non-Patent Citations (3)
| Title |
|---|
| Z.-Y.ZHOU,ET AL: "Neuroprotective effects of water-soluble Ganoderma lucidum polysaccharides on cerebral ischemic injury in rats", 《JOURNAL OF ETHNOPHARMACOLOGY》 * |
| 周心宇: "血栓通联合胞二磷胆碱治疗急性脑梗塞60例", 《西部中医药》 * |
| 张安: "天麻素注射液联合大剂量胞二磷胆碱治疗急性脑梗死", 《临床研究》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113244324A (en) * | 2021-03-04 | 2021-08-13 | 南京焰帆生物技术有限公司 | Citicoline combined medicine and preparation method and application thereof |
| CN114955031A (en) * | 2022-05-27 | 2022-08-30 | 山东希尔康泰药业有限公司 | Diclofenac sodium lidocaine hydrochloride injection aseptic preparation system |
| CN114955031B (en) * | 2022-05-27 | 2023-09-22 | 山东希尔康泰药业有限公司 | Sterile preparation system for diclofenac sodium lidocaine hydrochloride injection |
Also Published As
| Publication number | Publication date |
|---|---|
| PH12018050518A1 (en) | 2020-06-01 |
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