CN105078952A - Levodopa preparation and application thereof - Google Patents
Levodopa preparation and application thereof Download PDFInfo
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Abstract
The invention relates to levodopa preparation and application thereof. The levodopa preparation comprises, by weight percentage, 70-90% of levodopa and 10-30% of benserazide. The levodopa preparation has the advantages that the levodopa preparation contains the levodopa and the benserazide of fixed content, is applicable to rehabilitation treatment of cerebral dysfunction after cerebral resuscitation, and provides medicine for treating cerebral dysfunction caused by hypoxia-ischemia brain damage after cardio-pulmonary resuscitation; the preparation can be used to prepare medicine for repairing cerebral ischemia-reperfusion injury, medicine for the rehabilitation treatment of cerebral dysfunction after cerebral resuscitation, medicine for treating hypoxia-ischemia brain damage and medicine for replenishing body dopamine; meanwhile, a new purpose of levodopa is provided.
Description
Technical field
The present invention relates to field of medicaments, in particular to a kind of Dopar and application thereof.
Background technology
Along with the continuous progress of medical level, cardio-pulmonary resuscitation technology in recent years improves constantly, but the brain function after success of cardiopulmonary resuscitation recovers not exclusively to remain the significant obstacle affecting Rehabilitation.
According to statistics, the patient of cardiopulmonary successful resuscitation only has 10% ~ 30% to recover good, and in survivor, great majority exist the disordered brain functioies such as consciousness, language, cognition, motion.Up to now, remedy measures for cerebral resuscitation is very limited, relatively more conventional is early stage shortening to greatest extent cycle interruption time (no-flowtime) and brain Low perfusion time (low-flowtime), namely the cardio-pulmonary-cerebral resuscitation (CPCR) of effective rhythm of the heart is recovered rapidly, and cryotherapy, hyperbaric oxygen therapy etc.
The early cerebral protection measure of relatively generally acknowledging at present is cryotherapy; but there is serious obstacle in it; namely while induced low temperature, can with the side reaction such as rising occurring shiver with cold, catecholamine and corticoid level, and then significantly reduce the speed of induced low temperature, degree and treatment curative effect.In addition, in prior art, almost do not report specially for the medicine that the brain of the early intervention of the disordered brain function occurred because of ischemic-hypoxic brain injury after cardio-pulmonary resuscitation is protected.
In view of this, special proposition the present invention.
Summary of the invention
An object of the present invention is to provide a kind of Dopar, said preparation contains levodopa and the benserazide of set content, can be used in the handicapped rehabilitation of cerebral resuscitation hindbrain, for the disordered brain function occurred because of ischemic-hypoxic brain injury after cardio-pulmonary resuscitation provides Drug therapy.
Two of object of the present invention is to provide the purposes of described Dopar, applies in the many-side of the rehabilitation of disordered brain function to realize said preparation.
In order to realize above object, spy of the present invention by the following technical solutions:
A kind of Dopar, it is characterized in that, according to percent by weight, it comprises: levodopa 70% ~ 90%, benserazide 10% ~ 30%.
The maintenance of body tissue organ homergy, function, depends on good blood circulation.The local organization organ ischemia that a variety of causes causes, usually make histiocyte generation ischemia injury, meanwhile, after recovering blood reperfusion under certain condition, body cell functional metabolism obstacle and structural deterioration not only do not alleviate and increase the weight of further on the contrary, are ischemical reperfusion injury (ischemia-reperfusioninjury).
Patient after success cardio-pulmonary resuscitation, the disordered brain function occurred because of ischemic-hypoxic brain injury becomes a large difficult point for the treatment of and rehabilitation after cerebral resuscitation.Have research display, after Therapy of Severe Brain Injury cerebral cortex function infringement and Limbic system of brain is impaired substantial connection, particularly dopaminergic neuron is impaired relevant.Dopaminergic neuron relies on aerobic metabolism, very responsive to anoxia.After there is cerebral hypoxia ischemia damage, dopaminergic neuron is destroyed.After ischemia-reperfusion, dopamine D_2 receptors minimizing causes dopamine related neurotransmitters system imbalance.Therefore, the Therapeutic Method supplementing dopamine can improve the problem of dopamine related neurotransmitters system imbalance, but dopamine itself is not by blood brain barrier, and levodopa can be exchanged into dopamine under the effect of aromatic series L2 amino acid decarboxylases, thus supplement dopamine.
This preparation provided by the invention, its active component is levodopa, and after medication, levodopa, in body, is dopamine by the role transformation of decarboxylase.The mechanism that dopamine can be used as, behavior subconscious on cortex and motor adjustment plays the neurotransmitter of last activation/impact.Under normal circumstances, dopaminergic neuron is present in substantia nigra of midbrain compact part, Ventral Midbrain tegmental region [of Forel and hypothalamus.Wherein, be positioned at the dopaminergic neuron (also known as A10 neuron) of Ventral Midbrain tegmental region [of Forel, mainly send Fiber Projections to limbic system's cortex as before central forebrain (orbitofrontal cortex), intranasal district, cingulum time, septal area, amygdaloid body etc.; Therefore, these Fiber Projections are otherwise known as mesolimbic dopaminergic system, and its function and the consciousness of people, awake, emotion, ergasia etc. adjustment are relevant.
Comprehensive, in cerebral resuscitation process, use Dopaminergic Drugs (if active substance is the medicine of levodopa) replacement therapy, contribute to DA-ergic nervous pathway in rebuilding body, thus make disordered brain function repaired.In addition, after levodopa is taken, about have 95% can change into dopamine in periphery through DOPA decarboxylase decarboxylation and consume, only have an appointment in the levodopa arrival brain of 1%.Therefore, levodopa is suppressed to be necessary especially at the outer decarboxylation of brain.This preparation of the present invention, it contains a certain amount of benserazide, and benserazide is periphery dopa decarboxylase inhibitor, can effectively prevent this levodopa outer by decarboxylation at brain.Therefore, the preparation be made up of levodopa and benserazide its periphery DOPA decarboxylation can be stoped to become dopamine, make in blood, have more levodopa to enter in brain and become dopamine, the requirement of levodopa can be made like this to reduce (about 75-80%), periphery side effect can be reduced or eliminated again.Make said preparation effectively can play the handicapped rehabilitation effect of cerebral resuscitation hindbrain, thus make up the blank of this field Chinese medicine and overcome many defects that traditional cryotherapy exists.
Preferably, according to percent by weight, it comprises: levodopa 75% ~ 85%, benserazide 15% ~ 25%.
Preferably, according to percent by weight, it comprises: levodopa 75% ~ 85%, benserazide 15% ~ 25%.
Preferably, the dosage form of said preparation is tablet.
Preferably, described Dopar is madopar.
Dopar is applied in for the preparation of reparation cerebral ischemia reperfusion injury medicine.
Dopar is applied in the medicine for the preparation of the handicapped rehabilitation of cerebral resuscitation hindbrain.
Dopar is applied in the medicine for the preparation of the damage for the treatment of cerebral hypoxia ischemia.
Dopar supplements application in the medicine of dopamine being prepared as body.
The application of Dopar in the medicine of preparation treatment disturbance of consciousness.
Compared with prior art, technique effect of the present invention comprises the following aspects:
1), said preparation is that rehabilitation after cerebral resuscitation provides a kind of brain-protection drugs; this medicine can improve the disturbance of consciousness of the patient of persistent coma after cerebral resuscitation significantly; overcome the defect of the side reaction such as rising of shiver with cold that traditional cryotherapy exists, catecholamine and corticoid level, also compensate for the blank of the therapeutic process Chinese medicine of cerebral resuscitation simultaneously.
2), ripe madopar can be adopted as Dopar; Because madopar have passed clinical experiment, therefore can be directly used in the cerebral resuscitation first aid of patient, for this medicine provides a kind of new purposes.
3), this Dopar (comprising madopar), test known by interior animal experiment and external in vitro cell culture, said preparation is by supplementary dopamine and then obviously reduce cerebral ischemia reperfusion injury, so imply that said preparation as or for the preparation of the medicine of the handicapped rehabilitation of cerebral resuscitation hindbrain, the damage for the treatment of cerebral hypoxia ischemia medicine, supplement for body dopamine medicine and repair in the application of cerebral ischemia reperfusion injury medicine.
Accompanying drawing explanation
The water maze movement locus figure that Fig. 1 provides for test example 1 of the present invention;
Wherein, 1 is sham operated rats, and 2-a is model group 1w subgroup, and 2-b is model group 2w subgroup, and 3-a is small dose group 1w subgroup, and 3-b is small dose group 2w subgroup, and 4-a is heavy dose of group 2w subgroup, and 4-b is heavy dose of 1w subgroup;
Fig. 2 is that in test example 1 of the present invention, after Reperfu-sion 1w and 2w, each group rat escape latency compares;
Wherein, 2-1 is after Reperfu-sion 1w, and 2-2 is after Reperfu-sion 2w;
Fig. 3 be in test example 2 of the present invention HT22 cell glycosyloxy deprive/reoxygenation model in cytoactive result;
Fig. 4 be in test example 2 of the present invention dopamine on HT22 cell glycosyloxy deprive/reoxygenation injury cellular morphology affect result figure;
Fig. 5 be in test example 2 of the present invention HT22 cell glycosyloxy deprive/reoxygenation injury in dopamine hydrochloride result is affected on cytoactive;
Fig. 6 be in test example 2 of the present invention HT22 cell glycosyloxy deprive/reoxygenation injury in dopamine hydrochloride result is affected on cell survival rate.
Detailed description of the invention
Below in conjunction with embodiment, embodiment of the present invention are described in detail, but it will be understood to those of skill in the art that the following example only for illustration of the present invention, and should not be considered as limiting the scope of the invention.Unreceipted actual conditions person in embodiment, the condition of conveniently conditioned disjunction manufacturer suggestion is carried out.Agents useful for same or the unreceipted preparation manufacturer person of instrument, be and can buy by commercially available the conventional products obtained.
Embodiment 1
Dopar, according to percent by weight, comprises levodopa 70%, benserazide 30%; Conventional preparation method is adopted to make tablet.
Embodiment 2
Dopar, according to percent by weight, comprises levodopa 80%, benserazide 20%, adopts conventional preparation method to make tablet.
Embodiment 3
Dopar, according to percent by weight, comprises levodopa 90%, benserazide 10%, adopts conventional preparation method to make tablet.
Embodiment 4
Dopar, according to percent by weight, comprises levodopa 75%, benserazide 25%, adopts conventional preparation method to make tablet.
Embodiment 5
Dopar, according to percent by weight, comprises levodopa 85%, benserazide 15%, adopts conventional preparation method to make tablet.
Embodiment 6
This Dopar is madopar, and dosage form is tablet (125mg specification), containing levodopa 100mg and benserazide 25mg.
Embodiment 7
This Dopar is madopar, and dosage form is tablet (200mg specification), containing levodopa 200mg and benserazide 50mg.
Should be understood that described levodopa and benserazide are only the active ingredient of said preparation in above-mentioned all embodiments and claimed Dopar, namely both percentage by weights are only the ratio at active ingredient.
Test example 1 active component levodopa affects the neuroethology of global cerebral ischemia/reperfusion rat
1 research contents and method
Healthy adult male SD rat 176, is divided into sham operated rats (n=20) at random, model group (n=52), low dose of levodopa intervention group (n=52), heavy dose of levodopa intervention group (n=52).Model group and pharmaceutical intervention group are divided into 1 week group, 2 weeks groups and 4 weeks groups after modeling according to the difference of time point.
Improvement Pu1Sinelli tetra-vascular occlusion method (4-VO) is adopted to make global cerebral ischemic-reperfusion rat model.Pharmaceutical intervention group rat in Reperfu-sion at once, 1d, 2d, 3d, 4d, 5d, 6d intraperitoneal injection levodopa 25mg/kg (low dose of intervention group) or 50mg/kg (heavy dose of intervention group), sham-operation and model control group give normal saline 25mg/kg lumbar injection at same time point.
Observe each group of rat improvement neural reflex (NSS) scoring respectively.After Reperfu-sion, wherein during 1w, choose 32 rats (often organize 6), choose 24 rats (model group and two medicine group each 8) during 2w and carry out Morris water maze laboratory.
2 results of study
(1) NSS scoring is improved
The score value difference of four groups of rats after Reperfu-sion when 6h, 24h, 72h, 1w has statistical significance (p<0.05), wherein model group scoring is higher than sham operated rats and medicine group (p<0.05), but the indifference opposite sex (p>0.05) between various dose medicine group.Extend in time, each group scoring is all on a declining curve.After Reperfu-sion when 2w, 3w, 4w, 4 groups of scorings no difference of science of statistics (p>0.05), the results are shown in Table 1.
Table 1 levodopa experimental group respectively organizes rat Reperfu-sion one week interior improvement NSS scoring
* compared with sham operated rats, p<0.05; # compared with model group, p<0.05.
(2) Morris water maze laboratory
Please refer to Fig. 1 and Fig. 2, result explanation, difference between each group of rat escape latency every day has statistical significance (p<0.05), wherein, sham operated rats incubation period is compared with other three groups short (p<0.05), pharmaceutical intervention group is starkly lower than model group (p<0.05), but no difference of science of statistics incubation period (p>0.05) of various dose medicine group.Along with the increase of frequency of training, the incubation period of each group rat shortens (p<0.05) all gradually.In explorative experiment, model group and two medicine groups are starkly lower than sham operated rats (p<0.05) at the second quadrant holdup time percentage ratio, and medicine group longer than model group (p<0.05), but there was no significant difference (p<0.05) between two different dose drug groups.
Test example 2 in vitro cell culture experimental section
(1) research contents and method
1 neuronal cell cultures
HT22 cell is a kind of hippocampus neurons in mice cell line, is a kind of sub-clone of mice T4 cell line.In cerebral tissue, hippocampal neuron is more responsive to anoxia, and therefore, this test example selects HT22 cell as object of study.HT22 cell culture used medium is the DMEM in high glucose culture medium containing 10% hyclone.HT22 cell routine is incubated at 37 DEG C, equilibrium humidity, cultivates containing in the standard CO2 gas incubator of 5% carbon dioxide.
2 glycosyloxies deprive the foundation of/reoxygenation (OGD/R) HT22 cell model
In vitro models is the ischemical reperfusion injury that the mode using glycosyloxy to deprive complex sugar reoxygenation again simulates at body.Plating cells, in 96 orifice plates, changes sugar-free serum-free medium in second day, is then positioned over 37 DEG C, equilibrium humidity, cultivates containing in the incubator of 5% carbon dioxide and 95% nitrogen.
Anoxia is tested:
1. glycosyloxy deprives group, by cultured cells by above-mentioned steps anoxia 3h, 8h, 12h, 18h respectively;
2. matched group, has the cultivation of serum normally to cultivate based on containing in the standard CO2 gas incubator of 5% carbon dioxide with there being sugar cultured cells.
Reoxygenation is tested:
1. reoxygenation group, first by after cell as stated above anoxia 18h, cultured cells being changed sugar has the cultivation of serum to cultivate 10h and 20h based on containing normal in the standard CO2 gas incubator of 5% carbon dioxide;
2. matched group, normally cultivates.
3 dosage regimens
Carry out 4 groups of experiments, comprise matched group, glycosyloxy deprives/reoxygenation model group, dopamine hydrochloride medicine group.Because isolated experiment does not relate to the problem of agent permeates therethrough blood brain barrier, therefore, medicine is directly dissolved in culture medium can reaches administration object.Levodopa by blood brain barrier, but water insoluble, be difficult to add in culture medium, therefore isolated experiment dopamine hydrochloride replaces, and reaches the object of dopamine administration.Medicine arranges 25 μm of ol/L, 50 μm of ol/L and 100 μm ol/L, tri-kinds of concentration.And at following 4 time points, medicine is added in cell culture substrate respectively, detect after cell reoxygenation terminates:
(OGD) 2h (before anoxia 2h administration) before the phase is deprived at glycosyloxy;
(anoxia administration) in phase process is deprived at glycosyloxy;
The reoxygenation phase (reoxygenation administration);
Whole experimentation all adds medicine (omnidistance administration).
4 image acquisition analyses
Cell image adopts Nikon ECLIPSETi series microscope imaging system to gather under X10 times of object lens, and application AdobePhotoshopCS2 and imageJ software carries out picture analyzing.
5.LDH cell viability detects
Cell viability detects and uses LDH detection means, after cell model completes or after drug treating completes, every hole adds 150 μ lLDH releasing agents, and cell culture incubator hatches 2h.Get 120 μ l supernatants and add 60 μ lLDH testing liquid, in microplate reader, then carry out 490nm and 650nm dual wavelength measure absorbance.Result optical density value represents (opticaldensity (OD)).
6AnnexinVPE/7-AAD FCM analysis method
After cell model completes, use AnnexinVPE/7-AAD test kit (BDBiosciencesPharmingen, SanJose, CA), control tube, mend and long pipe is set and sample tube dyes simultaneously, get single cell suspension cell 1 × BingdingBuffer and cell is adjusted to 1 × 10
6/ ml concentration, gets 100 microlitres and goes to 5 milliliters of streaming Special test tubes, add 5 microlitre AV-PE respectively.Mixing cell, after lucifuge hatches 15min, adds upper machine (BDAriaII) within 5 microlitre 7-AAD solution and 400 microlitre 1xBingdingBuffer1h and detects.
(2) result
1HT22 cell glycosyloxy deprives/reoxygenation (OGD/R) cell model result
In order to determine that best glycosyloxy deprives time and reoxygenation time, glycosyloxy deprive the phase and glycosyloxy deprive/vigor of reoxygenation phase damaging cells and the vigor of cellular control unit compare, the experimental technique of employing is LDH experiment.
When only anoxia 18h not reoxygenation time, cell viability obviously declines (OD0.983 ± 0.129, p < 0.05 and contrast ratio) (Fig. 3, A).When anoxia duration is 18h, 2 the reoxygenation durations (10h and 20h) selected all can cause obvious damage (Fig. 3 of cell, B), wherein the damage difference of OGD18h/R10h extremely significantly (OD0.689 ± 0.082, p < 0.01 and contrast ratio).The condition that this experiment will select OGD18h/R20h (OD1.230 ± 0.096, p < 0.05 and contrast ratio) to set up as model, because this time point is conducive to the performance of medicament adjusting effect.
In figure 3, show HT22 cell glycosyloxy to deprive/reoxygenation model under cytoactive situation, wherein, cytoactive situation by LDH cytoactive test determine.Concrete, A: when reoxygenation duration is 0h, HT22 cytoactive situation under different anoxia duration; B: when anoxia duration is 18h, HT22 cytoactive situation under different reoxygenation duration; * p < 0.05, * * p < 0.01 is compared with respective contrast.
2 dopamine hydrochlorides deprive the effect of reoxygenation injury to HT22 cell glycosyloxy
2.1 reoxygenation administrations affect HT22 morphocytology
HT22 cell is observed under an optical microscope, and cell space is tapered or circular, and projection is long, is interconnected to network-like.Neuron is deprived after reoxygenation process 38h through glycosyloxy again, and most cells maintains normal cell form, and partial nerve unit projection length shortens, and impaired severe patient even disappears (in Fig. 4 C and D).Before anoxia, 2h, anoxia, reoxygenation and whole process add 25mol/l, 50mol/l, 100mol/l dopamine hydrochloride respectively, can be observed Growth of Cells in reoxygenation administration group intensive and maintain normal cellular morphology (K in Fig. 4, L and M), and due to glycosyloxy deprive/shrinkage round cell that reoxygenation causes almost disappears.
The cell great majority of 2h administration before anoxia maintain normal cell form (in Fig. 4 E, F and G).In anoxia administration group and omnidistance administration group, cell does not almost have the cell of normal morphology, and most cells is crimped to circle, and forms bulk, cell injury serious (in Fig. 4 H, I, J, N, O and P).During variable concentrations administration, cellular morphology no significant difference.
Wherein, to be dopamine deprive the/impact of reoxygenation injury cellular morphology to HT22 cell glycosyloxy to Fig. 4.A, B are matched group; C, D are model group; E, F, G are 2h administration group before anoxia; H, I, J are anoxia administration group; K, L, M are reoxygenation administration group; N, O, P are omnidistance administration group.Wherein, the administration concentration of E, H, K, N is 25mol/l; The administration concentration of F, I, L, O is 50mol/l; The administration concentration of G, J, M, P is 100mol/l.Length of the scale is 50 μm.
2.2 reoxygenation administrations are on the impact of Cell viability
2.2.1.LDH drug detection experimental result
The detection that dopamine hydrochloride variable concentrations and time point administration affect for cell viability, the statistical method of employing is two-way analysis of variance.
Experimental result (Fig. 5) shows, when reoxygenation administration, cell viability (is 0.204 with the equal value difference of OD value of model group higher than OGD18h/R20h model group, p < 0.05 and model ratio), but be still less than matched group (be-0.451, p < 0.01 and contrast ratio with the equal value difference of OD value of matched group).
When before anoxia during 2h administration, cell viability and model group zero difference.But, when anoxia administration or omnidistance administration, increase the weight of (Wei-0.538 and-0.543 with the OD value mean difference of model group, be p < 0.01 with model ratio) than cell injury with model.But, zero difference between three kinds of drug level.
In Figure 5, show HT22 cell glycosyloxy to deprive/reoxygenation injury in dopamine hydrochloride on the impact of cytoactive.Wherein, matched group and the not administration of OGD18h/R20h model group, the administration concentration of other groups is 25 μm of ol/L, 50 μm of ol/L and 100 μm ol/L; * p < 0.01 and contrast ratio; #p < 0.05, ##p < 0.01 and OGD18h/R20h model ratio.
2.2.2.AnnexinVPE/7-AAD flow cytomery result
The testing result of morphocytology result and LDH release all shows dopamine hydrochloride and has nothing to do to the repair of HT22 cell ischemical reperfusion injury and concentration, therefore, only AnnexinVPE/7-AAD flow cytometer detection is done to dopamine hydrochloride 50mol/L, to reaffirm that dopamine hydrochloride deprives some repair time of reoxygenation injury to HT22 cell glycosyloxy.Statistical method used is one factor analysis of variance.As shown in Figure 6, the percent living cells in reoxygenation administration group is higher than OGD18h/R20h model group (be 0.1266667, p < 0.05 with the equal value difference of percent living cells value of model group, with model than) for streaming result.When before anoxia during 2h administration, cell viability and model group zero difference.But when anoxia administration or omnidistance administration, with model ratio, cell injury increases the weight of (Wei-0.764000 and-0.764333 with the percent living cells value mean difference of model group, be p < 0.01 with model ratio).Not but, zero difference between three kinds of drug level.
In Fig. 6, show HT22 cell glycosyloxy to deprive/reoxygenation injury in dopamine hydrochloride on the impact of cytoactive.Wherein, matched group and the not administration of OGD18h/R20h model group, administration concentration is 50 μm of ol/L; * p < 0.05, * * p < 0.01 and contrast ratio; #p < 0.05, ##p < 0.01 and OGD18h/R20h model ratio.
Result shows, and when reoxygenation, supplements dopamine (providing preparation directly to provide by the embodiment of the present invention) have the effect that anti-glycosyloxy deprives reoxygenation injury to Hippocampal Neuron Cells.The experiment in vivo result that this result and pre-stage test example 1 are lifted and the clinical study results that following test example 3 is lifted conform to, and namely after Reperfu-sion administration, the consciousness of patient there occurs improvement.Therefore, supplement this therapeutic modality of dopamine during reoxygenation, for cerebral ischemia reperfusion injury, there is protective effect.
Test example 3
Case: totally 4 examples; Take to for examination person the Dopar (madopar) that the embodiment of the present invention 7 provides, usage is oral, a 250mg, three administrations on the one.
Protopathy or the CA cause of disease of each patient are respectively:
Patient 1, sleep apnea syndrome;
Patient 2, bacterial pneumonia, CPM, intractable hyponatremia;
Patient 3, emphysema, pulmonary heart disease, respiratory failure;
Patient 4, hypertension, coronary heart disease, respiratory failure.
In addition, for age, the sex of patient, CA (cardiacarrest) time-histories, restoration of spontaneous circulation (restorationofspontaneouscirculation, ROSC) time-histories (cardio-pulmonary resuscitation starts, to circulation recover time-histories) etc. information refer to following table.
In addition, table 2 also show process, the prognosis information of each case; Concrete outcome please refer to table 2.
The table 2 patient CA cause of disease, time-histories, ROSC time-histories, process and prognosis situation
Therapeutic process: medication respectively, every day 2-3 time.After CA 5-20d use, continuous 7-21d or to during patient awoke stop using.All stupor is just there is in disease in patient after generation acute ischemia anoxic brain injury.After CA in 3d Glasgow Coma Score (GCS) between 3-6 divides, average 3.4 points.Within after recovery 11d-3 month, again carry out GCS scoring, mark, between 8-15, is equally divided into 13 points.Wherein have 2 examples to reach full marks 15 points, neurological functional recovery, can take care of oneself daily life; 1 example is 14 points; 1 routine state of consciousness is lethargy.
This experimental result finds, the 4 routine patients after a procedure all state of consciousness of 1d to 1 make moderate progress.Above result prompting, in the therapeutic process of cerebral resuscitation, by supplementary neurotransmitter, patient's disturbance of consciousness may obtain recovery to a certain extent.
In sum, binding tests example 1,2 and 3 known, this Dopar (comprising madopar) provided by the invention, after making cerebral resuscitation, the disturbance of consciousness of the patient of persistent coma makes moderate progress; And by showing with isolated experiment in body, supplementary dopamine obviously can reduce cerebral ischemia reperfusion injury; Therefore, this Dopar can as the brain-protection drugs of the rehabilitation after cerebral resuscitation, also for madopar opens a kind of new purposes; Imply that the medicine madopar of this Dopar or maturation, it can for the preparation of the medicine of the handicapped rehabilitation of cerebral resuscitation hindbrain, for the preparation of the medicine for the treatment of cerebral hypoxia ischemia damage, for the preparation of repairing cerebral ischemia reperfusion injury medicine, being prepared as in the application that body supplements in the medicine of dopamine and the medicine of preparation treatment disturbance of consciousness.
In addition, the active component due to said preparation is levodopa (having another name called levodopa (L-dopa)), is antiparkinsonian drug.It enters cerebral tissue by blood brain barrier, plays a role.Be applicable to primary parkinsonism and non-medicine originality Parkinsonism.And in the present invention; make use of another performance of levodopa, it can be used in the handicapped rehabilitation of cerebral resuscitation hindbrain, therefore; the present invention also provides new purposes for levodopa, and namely the purposes of levodopa in above-mentioned enumerated several fields also belongs to protection scope of the present invention.
Although illustrate and describe the present invention with specific embodiment, however it will be appreciated that can to make when not deviating from the spirit and scope of the present invention many other change and amendment.Therefore, this means to comprise all such changes and modifications belonged in the scope of the invention in the following claims.
Claims (10)
1. a Dopar, is characterized in that, according to percent by weight, it comprises:
Levodopa 70% ~ 90%, benserazide 10% ~ 30%.
2. Dopar as claimed in claim 1, it is characterized in that, according to percent by weight, it comprises:
Levodopa 75% ~ 85%, benserazide 15% ~ 25%.
3. Dopar as claimed in claim 1, it is characterized in that, according to percent by weight, it comprises:
Levodopa 80%, benserazide 20%.
4. the Dopar as described in any one of claim 1-3, is characterized in that, the dosage form of said preparation is tablet.
5. Dopar as claimed in claim 4, it is characterized in that, described Dopar is madopar.
6. the Dopar described in any one of claim 1-5 is applied in for the preparation of reparation cerebral ischemia reperfusion injury medicine.
7. the Dopar described in any one of claim 1-5 is applied in the medicine for the preparation of the handicapped rehabilitation of cerebral resuscitation hindbrain.
8. the Dopar described in any one of claim 1-5 is applied in the medicine for the preparation of the damage for the treatment of cerebral hypoxia ischemia.
9. the Dopar described in any one of claim 1-5 supplements application in the medicine of dopamine being prepared as body.
10. the application of the Dopar described in any one of claim 1-5 in the medicine of preparation treatment disturbance of consciousness.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107951875A (en) * | 2017-12-05 | 2018-04-24 | 王增强 | A kind of composite preparation containing levodopa |
| CN113081994A (en) * | 2021-04-20 | 2021-07-09 | 杭州泓友医药科技有限公司 | Compound medicine for treating Parkinson's disease and preparation method thereof |
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| CN113081994A (en) * | 2021-04-20 | 2021-07-09 | 杭州泓友医药科技有限公司 | Compound medicine for treating Parkinson's disease and preparation method thereof |
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