CN101732331B - Composite of monostalotetrahexosylgangliside and glutamate - Google Patents
Composite of monostalotetrahexosylgangliside and glutamate Download PDFInfo
- Publication number
- CN101732331B CN101732331B CN2009100084769A CN200910008476A CN101732331B CN 101732331 B CN101732331 B CN 101732331B CN 2009100084769 A CN2009100084769 A CN 2009100084769A CN 200910008476 A CN200910008476 A CN 200910008476A CN 101732331 B CN101732331 B CN 101732331B
- Authority
- CN
- China
- Prior art keywords
- sodium
- glutamic acid
- monostalotetrahexosylgangliside
- injection
- compositions
- 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.)
- Active
Links
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of medicines, particularly relates to a composite of monostalotetrahexosylgangliside and glutamate, and also provides a method for preparing an injection liquid preparation of the composite, and application in preparing the medicaments for treating vascular or traumatic central lesion and parkinson's disease.
Description
1, technical field
The invention belongs to medical technical field; Be specifically related to the compositions of a kind of Monostalotetrahexosylgangliside sodium and glutamic acid, and said composition is used for treating the purposes of vascular or traumatic central nervous system injury and parkinsonian medicine in preparation.
2, background technology
Ganglioside (Gangliosides) is to contain sialic TANGSHEN through sphingolipid; Be present in the mammal cell membrane; Content is especially abundant in the nervous system, is the constituent of neuron membrane, in nerve generation, growth, atomization, plays requisite effect; Nerve reparation for after the damage is also extremely important, has the neuranagenesis of promotion, neural axon growth and synapse and forms, recovers the innervation function; Improve the recovery of nerve conduction, promotion brain electrical acti and other neuroelectricity physical signs; Effects such as protection cell membrane, the various enzymatic activity recoveries of promotion cell membrane.
Monostalotetrahexosylgangliside (GM1) is one of important ganglioside, in the treatment of central nervous system pathological change, plays an important role.GM1 can also be through keeping the Na on the axoneure film except that the combined effect with above-mentioned ganglioside
+-K
+-ATP enzyme and Ca
2+-Mg
2+The activity of-ATP enzyme plays and keeps the inside and outside ionic equilibrium of cell, alleviates the neurocyte edema, prevents Ca in the cell
2+The effect of gathering; GM1 can resist the neurotoxic effect of excitatory amino acid, reduces the infringement of radical pair neurocyte etc.Therefore, Monostalotetrahexosylgangliside (GM1) can promote nerve remodeling and the functional rehabilitation behind the central nervous system injury that a variety of causes causes, and vascular or traumatic central nervous system injury and parkinson etc. are had curative effect preferably.
Ganglioside molecule water-wet side is close with hydrophobic side length, very easily in water, form stable micelle state, is unfavorable for the preparation of ejection preparation.Patent WO9317691 processes sodium salt with Monostalotetrahexosylgangliside; Injection formulation is cooked buffer with phosphate; Sodium chloride is done isoosmotic adjusting agent, has effectively solved Monostalotetrahexosylgangliside and in water, has formed micellelike state, the difficult problem of medicine preparation.Yet the sodium salt that should write out a prescription influences Monostalotetrahexosylgangliside biomembrane and blood-brain barrier permeability, thereby brain blood drug level is low, and can't maintain for a long time more than the treatment concentration, greatly reduces clinical use curative effect.Therefore be badly in need of seeking a kind of new, can improve Monostalotetrahexosylgangliside sodium and cross biomembrane and blood brain barrier rate, the high method of clinical use curative effect.
Glutamic acid is as the oxidized aminoacid of the unique ability of cerebral tissue, and its intravital product glutamine can be used as the energy matter of cerebral tissue, improves and keeps cerebral function.Glutamic acid is as nerve centre and corticocerebral tonic, for treatment cerebral concussion or nerve injury, epilepsy and to the mentally retarded child certain curative effect arranged all.Therefore we select for use Monostalotetrahexosylgangliside sodium and glutamic acid to prepare compositions research; A large amount of experimental results show; Under certain proportioning; Glutamic acid also demonstrates the effect that increases the GM1 brain targeting in the compositions except containing above-mentioned effect, has promoted the blood-brain barrier permeability of Monostalotetrahexosylgangliside sodium effectively; Simultaneously, glutamic acid also plays the effect that makes GM1 stable.
3, summary of the invention
The purpose of this invention is to provide a kind of have the Monostalotetrahexosylgangliside sodium of good blood-brain barrier permeability and clinical efficacy and the compositions of glutamic acid.
Another object of the present invention provides the preparation of compositions method of a kind of Monostalotetrahexosylgangliside sodium and glutamic acid.
The compositions that an also purpose of the present invention provides Monostalotetrahexosylgangliside sodium of the present invention and glutamic acid is used for treating the purposes of vascular or traumatic central nervous system injury and parkinsonian medicine in preparation.
Technical scheme of the present invention is following:
A kind of compositions that contains Monostalotetrahexosylgangliside sodium and glutamic acid is characterized in that the weight ratio between Monostalotetrahexosylgangliside sodium and the glutamic acid is between 5: 1 to 60: 1.
The described compositions that contains Monostalotetrahexosylgangliside sodium and glutamic acid is characterized in that the weight ratio between Monostalotetrahexosylgangliside sodium and the glutamic acid is between 10: 1 to 40: 1.
The described compositions that contains Monostalotetrahexosylgangliside sodium and glutamic acid is characterized in that the weight ratio between Monostalotetrahexosylgangliside sodium and the glutamic acid is between 15: 1 to 30: 1.
The described compositions that contains Monostalotetrahexosylgangliside sodium and glutamic acid is characterized in that, the weight ratio between Monostalotetrahexosylgangliside sodium and the glutamic acid is 20: 1.
The described compositions that contains Monostalotetrahexosylgangliside sodium and glutamic acid is characterized in that, the described compositions that contains Monostalotetrahexosylgangliside sodium and glutamic acid is an injection formulation.
Described injection, wherein adjuvant is isoosmotic adjusting agent or pH regulator agent, osmotic pressure regulator commonly used comprises sodium chloride, glucose, potassium chloride, magnesium chloride, calcium chloride, sorbitol etc., preferred sodium chloride; PH value regulator commonly used comprises acetic acid-sodium acetate, lactic acid, citric acid-sodium citrate, sodium dihydrogen phosphate-sodium hydrogen phosphate etc., preferably phosphoric acid sodium dihydrogen-sodium hydrogen phosphate.
Described injection is characterized in that, described pH regulator agent is sodium dihydrogen phosphate, sodium hydrogen phosphate and sodium hydroxide.
Described injection is characterized in that, described pH scope is between 7.0～8.0.
The method for preparing of described injection formulation is characterized in that, decides Monostalotetrahexosylgangliside sodium, glutamic acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, sodium chloride by the accurate title of prescription, gets water for injection; Add the Monostalotetrahexosylgangliside sodium that weighs up, slowly be stirred to complete dissolving, add glutamic acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, the sodium chloride that weighs up then successively, stir; The pH value of medicinal liquid is between 7.0～8.0 at this moment, and standardize solution is with 0.22 μ m filtering with microporous membrane, fill; Sealing by fusing, sterilization, cooling; Labeling is packed, and promptly gets the composite injection of Monostalotetrahexosylgangliside sodium and glutamic acid.
The present invention also provides the compositions that contains Monostalotetrahexosylgangliside sodium and glutamic acid, the application in preparation treatment vascular or traumatic central nervous system injury and parkinsonian medicine.
The compositions of Monostalotetrahexosylgangliside sodium of the present invention and glutamic acid, the proportioning of drug component gropes to sum up to draw through the inventor in a large number, and each set of dispense is than all having better curative effect.
Monostalotetrahexosylgangliside sodium of the present invention is compared with immediate prior art with the compositions of glutamic acid, has the following advantages:
1, the compositions of Monostalotetrahexosylgangliside sodium and glutamic acid has better biological film and the penetrating speed of blood brain barrier crossed, and has improved the use curative effect greatly.
2, the injection formulation of the compositions of Monostalotetrahexosylgangliside sodium and glutamic acid stability is better.
3, the compositions of Monostalotetrahexosylgangliside sodium and glutamic acid has long-acting in tissue, and its injection formulation can reduce administration number of times.
Below further set forth the beneficial effect of the compositions of Monostalotetrahexosylgangliside sodium of the present invention and glutamic acid, but should this compositions that is interpreted as Monostalotetrahexosylgangliside sodium of the present invention and glutamic acid only not had following beneficial effect through the pharmacological research experimental example.
Pharmacologically active in the body of the experimental example present composition
Test sample: the injection formulation of the compositions of Monostalotetrahexosylgangliside sodium and glutamic acid (20mg/ props up),
Self-control, method for preparing is seen embodiment.
Reference substance: GM-1 injection (20mg/ props up), commercial, the TRB pharmaceutical factory produces.
(1) mensuration of cerebrospinal fluid Chinese medicine concentration
Get 35 of new zealand rabbits, the about 2.5kg of body weight, male and female are not limit, and are divided into 7 groups at random, i.e. the composite injection group (being called for short the B group) of GM-1 injection group (being called for short the A group) and Monostalotetrahexosylgangliside sodium of the present invention and glutamic acid.Intravenous administration, different time extracts the 0.2mL cerebrospinal fluid and experimentizes after administration, is respectively 30min, 1h, 2h, 4h, 8h behind the injectable drug sample time.Get cerebrospinal fluid 0.1mL and add an amount of solvent suspendible 15min,, get the supernatant 20 μ L sample introductions, use high-performance liquid chromatogram determination with the centrifugal 1min of 10000r/min.The result sees table 1.
The mensuration of table 1 cerebrospinal fluid Chinese medicine concentration
Annotate: compare with the A group:
*P＜0.01.
Experimental result and conclusion: visible by table 1 experimental result; The composite injection preparation of Monostalotetrahexosylgangliside sodium of the present invention and glutamic acid is significantly improved than GM-1 injection formulation through the medication amount of blood brain barrier; The medication amount that the composite injection preparation that Monostalotetrahexosylgangliside sodium of the present invention and glutamic acid is described sees through blood brain barrier obviously increases; Improve the blood drug level in the cerebral tissue, thereby improved therapeutic effect; Experimental data also shows; After the composite injection preparation administration of Monostalotetrahexosylgangliside sodium of the present invention and glutamic acid; The drug level of target tissue raises fast and is stable; In tissue, have long-acting, thereby the composite injection preparation of Monostalotetrahexosylgangliside sodium of the present invention and glutamic acid can reduce administration number of times.Simultaneously; Under the identical dosage; GM1 and the glutamic acid weight proportion brain medication amount in 10: 1 to 40: 1 scopes is higher than GM-1, and GM1 and the effect of glutamic acid weight proportion in 15: 1 to 30: 1 scope all obviously (p＜0.01) be superior to GM-1.
(2) study on the stability
The composite injection preparation (being called for short the B group) of GM-1 injection formulation (being called for short the A group) and Monostalotetrahexosylgangliside sodium of the present invention and glutamic acid is placed in the bottle sealing respectively.In the environment of refrigerator (3～5 ℃), room temperature (20～25 ℃) and 37 ℃ (RH 75%), place, in 0,3,6 and the outward appearance of observing medicine in 12 months.The result sees table 2.
Table 2 stability experiment result
Experimental result and discussion: under all temps and time; The compositions color of Monostalotetrahexosylgangliside sodium of the present invention and glutamic acid is not seen significant change, and it is good that the material redispersibility under the different condition keeps, and no polymerism takes place; Compositions stable fine of Monostalotetrahexosylgangliside sodium of the present invention and glutamic acid is described; With respect to the GM-1 preparation more stable, be more suitable for long term storage, more be adapted to the big production of industry.
(3) to the therapeutical effect of Parkinson's disease (PD)
1, the inclined to one side side P of Rats of selectivity D model preparation
(1) operation is prepared: ripe healthy Wistar rat, male and female are not limit, body weight 150～200g.Animal is routine feeding in the cage at room temperature, non-fasting before the art.6-OHDA (6-OHDA, Sigma chemical Co. product) is dissolved in and is made into 0.2% solution in 0.02% the ascorbic acid liquid, and sealing is kept in Dark Place subsequent use in low temperature (20 ℃) refrigerator.Apomorphine (APO, Sig-chemical Co. product) is made into 0.01% solution for standby with distilled water, and above solution is strict aseptic.
(2) modelling: animal with 0.3% pentobarbital sodium 10mL/kg intraperitoneal injection of anesthesia after, be fixed on (gulf, river I type C) on the stereotaxic instrument.Under the aseptic condition, medisection rat calvarium portion skin is peeled off periosteum, exposes bregma (cross crotch), lambdoid suture.Use the Mus skull to be drilled in the requirements of operation position and bore the skull hole of a diameter, confirm right substantia nigra portion coordinate position as 5mm.At twice 6-OHDA is injected right substantia nigra portion by following coordinate position with 10 μ L microsyringes (production of Shanghai metrical instrument factory), set up right side selectivity P of Rats D animal model.The B coordinate system: external auditory meatus line (the ear bar point line of centres) is lower than tooth plate upper limb 5mm, i.e. level 0 plane to the doorstep.For the first time inject 4 μ L, pinpoint inclined plane is towards the mouth side, and coordinate is (Posterior bregma, PB) 3.0mm, median line right side (Median right lateral.MRL) 2.5mm, cerebral dura mater veutro (Ventral dural, VD) 8.6mm behind the bregma.For the second time inject 3 μ L, pinpoint inclined plane is towards the tail side, and coordinate is PB2.4mm, MRL 2.7mm, VD8.6mm.Injection speed 1 μ l/min, per injection finishes that let the acupuncture needle remain at a certain point 10min slowly pulls out pin (about 10min) with 1.0mm/min speed then.Operation finishes, and stops up the skull hole with the medical gelatin sponge, sews up the incision, and puts back in the cage and feeds.
(3) APO brings out the observation of animal circling behavior: modeling postoperative 14d, and animal lumbar injection 0.01%APO 10mL/kg brings out rat circling behavior (counterclockwise), and checking 6-OHDA is to the damage effect of substantia nigra of midbrain DA serotonergic neuron.Rotary speed reaches 6r/min (Φ 35cm/r) and is regarded as successfully the inclined to one side side form type of PD selectivity, and injection APO 10min opening entry writes down 30min altogether.
2, animal divides into groups and handles
Laboratory animal is divided into the composite injection preparation for treating group (being called for short the C group) of normal control group, PD group, Monostalotetrahexosylgangliside sodium and glutamic acid, 16 every group.By the experimental design requirement, when experiment finished, after the circling behavior that record APO brings out changed, the sacrificed by decapitation animal was got brain fast, in ice pan, separated the right side striatum.The BIAO and BEN of surveying MCa (mitochondrial calcium) adds the nitrated 24h of 0.5N hydrochloric acid, gets supernatant 0.2mL after centrifugal, adds 1%La-C l30.8mL mixing, with PE-503 type atom absorption photometric instrumentation calcium concentration; Another part measured the BIAO and BEN of CaM (calmodulin) and claimed weight in wet base earlier, uses EDTA (ethylenediaminetetraacetic acid) buffer (10mg/mg) homogenate then, measures.The normal control group is except that not all right operation, and all the other processing methods are the same.
Experimental result and discussion:
The content of table 3 normal control group, PD group and C group right side striatum MCa, CaM
Annotate: compare with the normal control group
*P＜0.01; Compare with the PD group
#P＜0.01.
Visible by table 3 experimental result, the composite injection preparation of Monostalotetrahexosylgangliside sodium of the present invention and glutamic acid greatly reduces the content of PD group right side striatum MCa, CaM, and PD is had the obvious treatment effect.
4, the specific embodiment
Below, foregoing of the present invention is done further to specify through the specific embodiment of embodiment form.But should this scope that is interpreted as the above-mentioned theme of the present invention only not limited to following examples.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.
The preparation of the composite injection preparation of embodiment Monostalotetrahexosylgangliside sodium of the present invention and glutamic acid
1, prescription
Prescription 1
Monostalotetrahexosylgangliside sodium 10g
Glutamic acid 1g
Sodium hydrogen phosphate 0.94g
Sodium dihydrogen phosphate 0.15g
Sodium chloride 6.8g
0.1mol/L sodium hydroxide is an amount of
Water for injection adds to 1000mL
Prepare 500 altogether
Prescription 2
Monostalotetrahexosylgangliside sodium 10g
Glutamic acid 0.5g
Sodium hydrogen phosphate 1.12g
Sodium dihydrogen phosphate 0.18g
Sodium chloride 7.0g
0.1mol/L sodium hydroxide is an amount of
Water for injection adds to 1000mL
Prepare 500 altogether
Prescription 3
Monostalotetrahexosylgangliside sodium 20g
Glutamic acid 3g
Sodium hydrogen phosphate 2.38g
Sodium dihydrogen phosphate 0.38g
Sodium chloride 16.0g
0.1mol/L sodium hydroxide is an amount of
Water for injection adds to 2000mL
Prepare 1000 altogether
Prescription 4
Monostalotetrahexosylgangliside sodium 10.0g
Glutamic acid 0.8g
Sodium hydrogen phosphate 1.18g
Sodium dihydrogen phosphate 0.18g
Sodium chloride 8.0g
0.1mol/L sodium hydroxide is an amount of
Water for injection adds to 1000mL
Prepare 500 altogether
Prescription 5
Monostalotetrahexosylgangliside sodium 20g
Glutamic acid 4g
Sodium hydrogen phosphate 2.18g
Sodium dihydrogen phosphate 0.35g
Sodium chloride 20.0g
0.1mol/L sodium hydroxide is an amount of
Water for injection adds to 2000mL
Prepare 1000 altogether
Prescription 6
Monostalotetrahexosylgangliside sodium 10g
Glutamic acid 0.6g
Sodium hydrogen phosphate 1.52g
Sodium dihydrogen phosphate 0.25g
Sodium chloride 8.0g
0.1mol/L sodium hydroxide is an amount of
Water for injection adds to 1000mL
Prepare 500 altogether
Prescription 7
Monostalotetrahexosylgangliside sodium 20g
Glutamic acid 0.5g
Sodium hydrogen phosphate 3.14g
Sodium dihydrogen phosphate 0.57g
Sodium chloride 25.0g
0.1mol/L sodium hydroxide is an amount of
Water for injection adds to 2000mL
Prepare 1000 altogether
2, preparation technology
1) decides Monostalotetrahexosylgangliside sodium, glutamic acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, sodium chloride by the accurate title of prescription;
2) get 60 ℃ of about 1800mL of (± 5 ℃) water for injection, add the Monostalotetrahexosylgangliside sodium that weighs up, slowly be stirred to complete dissolving;
3) add glutamic acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, the sodium chloride that weighs up, stirring and dissolving successively.This moment medicinal liquid pH value about 7.5;
4) put to room temperature, reuse water for injection is settled to 2000mL;
5) with 0.22 μ m filtering with microporous membrane,
6) detect transparency;
7) detection level;
8) getting above-mentioned filled with solution in the ampoule of 2mL through the liquid drugs injection racking room of GMP authentication;
9) sealing by fusing;
10) 120 ℃ of circulation steam sterilizations 30 minutes;
11) leak detection;
12) lamp inspection;
13) finished product is examined entirely;
14) labeling;
15) packing warehouse-in.
Claims (8)
1. a compositions that contains Monostalotetrahexosylgangliside sodium and glutamic acid is characterized in that, the weight ratio between Monostalotetrahexosylgangliside sodium and the glutamic acid is between 15: 1 to 30: 1.
2. the compositions that contains Monostalotetrahexosylgangliside sodium and glutamic acid as claimed in claim 1 is characterized in that, the weight ratio between Monostalotetrahexosylgangliside sodium and the glutamic acid is 20: 1.
3. like any described compositions that contains Monostalotetrahexosylgangliside sodium and glutamic acid of claim 1～2, it is characterized in that the described compositions that contains Monostalotetrahexosylgangliside sodium and glutamic acid is an injection formulation.
4. injection as claimed in claim 3, wherein adjuvant is isoosmotic adjusting agent or pH regulator agent.
5. injection as claimed in claim 4 is characterized in that, described pH regulator agent is sodium dihydrogen phosphate, sodium hydrogen phosphate and sodium hydroxide.
6. injection as claimed in claim 4 is characterized in that, its pH scope is between 7.0～8.0.
7. like the method for preparing of the said injection formulation of claim 3, it is characterized in that, decide Monostalotetrahexosylgangliside sodium, glutamic acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, sodium chloride, get water for injection by the accurate title of prescription; Add the Monostalotetrahexosylgangliside sodium that weighs up, slowly be stirred to complete dissolving, add glutamic acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, the sodium chloride that weighs up then successively, stir; The pH value of medicinal liquid is between 7.0～8.0 at this moment, and standardize solution is with 0.22 μ m filtering with microporous membrane, fill; Sealing by fusing, sterilization, cooling; Labeling is packed, and promptly gets the composite injection of Monostalotetrahexosylgangliside sodium and glutamic acid.
8. like the described application of compositions in preparation treatment vascular or traumatic central nervous system injury and parkinsonian medicine that contains Monostalotetrahexosylgangliside sodium and glutamic acid of any claim of claim 1～2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100084769A CN101732331B (en) | 2008-11-20 | 2009-02-03 | Composite of monostalotetrahexosylgangliside and glutamate |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810180025 | 2008-11-20 | ||
| CN200810180025.9 | 2008-11-20 | ||
| CN2009100084769A CN101732331B (en) | 2008-11-20 | 2009-02-03 | Composite of monostalotetrahexosylgangliside and glutamate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101732331A CN101732331A (en) | 2010-06-16 |
| CN101732331B true CN101732331B (en) | 2012-05-23 |
Family
ID=42456701
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009100084769A Active CN101732331B (en) | 2008-11-20 | 2009-02-03 | Composite of monostalotetrahexosylgangliside and glutamate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101732331B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104473885B (en) * | 2014-12-09 | 2017-02-22 | 山东新时代药业有限公司 | Monosialotetrahexosyl ganglioside sodium sterile powder injection |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993017691A2 (en) * | 1992-03-13 | 1993-09-16 | Fidia S.P.A. | Pharmaceutical compositions containing monosialoganglioside gm1 or a derivative thereof suitable for the treatment of parkinson's disease |
| CN1192139A (en) * | 1995-07-28 | 1998-09-02 | 国家研究委员会 | Use of agonists or antagonists of P2 purinoceptors for the prevention of g lutamate-evoked cytotoxicity |
| CN1413587A (en) * | 2001-10-25 | 2003-04-30 | 杜士明 | Application of ganglioside in preparation of antiepileptic |
| CN1799552A (en) * | 2005-01-06 | 2006-07-12 | 严家定 | Single sialic acid tetrahexose ganglioside preparation method |
-
2009
- 2009-02-03 CN CN2009100084769A patent/CN101732331B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993017691A2 (en) * | 1992-03-13 | 1993-09-16 | Fidia S.P.A. | Pharmaceutical compositions containing monosialoganglioside gm1 or a derivative thereof suitable for the treatment of parkinson's disease |
| CN1192139A (en) * | 1995-07-28 | 1998-09-02 | 国家研究委员会 | Use of agonists or antagonists of P2 purinoceptors for the prevention of g lutamate-evoked cytotoxicity |
| CN1413587A (en) * | 2001-10-25 | 2003-04-30 | 杜士明 | Application of ganglioside in preparation of antiepileptic |
| CN1799552A (en) * | 2005-01-06 | 2006-07-12 | 严家定 | Single sialic acid tetrahexose ganglioside preparation method |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101732331A (en) | 2010-06-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8017623B2 (en) | Dextromethorphan hydrochloride | |
| US11147820B2 (en) | Methods for treating GI tract disorders | |
| CN109748881A (en) | Cystathionie-γ-lyase (CSE) inhibitor | |
| JPH0367045B2 (en) | ||
| CA2781436A1 (en) | Arachidonic acid analogs and methods for analgesic treatment using same | |
| US11896598B2 (en) | Appetite suppressant compositions and methods thereof | |
| CN106413708A (en) | Medical application of nmda receptor antagonist and pharmaceutical composition thereof | |
| DE69821498T2 (en) | USE OF AMIFOSTIN | |
| CN105769846A (en) | GPR35 agonist and application thereof | |
| JP2019001798A (en) | Activity motivation improver | |
| US20030021772A1 (en) | Method for treating effects of sleep deprivation and jet lag with NADPH and NADPH | |
| JPH04230327A (en) | Method for preventing expression of tolerance against analgesic action of morphine and its analog | |
| CN101732331B (en) | Composite of monostalotetrahexosylgangliside and glutamate | |
| CN1961879A (en) | Pharmaceutical composition for nose administered in-situ gel spray of Huperzine A, preparation process and use thereof | |
| CN103110640B (en) | Pharmaceutical composition of injection ceftizoxime sodium and compound amino acid injection | |
| LU101026B1 (en) | Metformin hydrochloride/berbamine hydrochloride compound sustained-release suspension formulation and preparation method thereof. | |
| CN105311622B (en) | A kind of combination medicine that treating pain and its preparation, preparation method | |
| EP0448029B1 (en) | Novel pharmaceutical uses of forskolin derivatives | |
| DE2743704C2 (en) | Medicines containing L- or DL-phenylglycine | |
| CN106177962A (en) | Pharmaceutical composition containing Sarpogrelate is for treating or prevent the purposes of fatty liver, hepatic fibrosis and/or hepatic injury | |
| CN108210879A (en) | A kind of pharmaceutical composition for treating acute Cerebral bleeding and its application | |
| RU2189813C1 (en) | Antihypoxic medicinal agent | |
| US3639626A (en) | Suppressing the activity of plasmin in humans and animals with trans-4-(aminomethyl)-cyclohexane - 1 - carboxylic acid | |
| CN100441589C (en) | Puerarin compound containing water soluble group and its preparation and use | |
| CN114948944B (en) | Application of composition containing sulbactam sodium sulfate and amiodarone in preparation of drugs for treating arrhythmia |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C53 | Correction of patent for invention or patent application | ||
| CB03 | Change of inventor or designer information |
Inventor after: Che Fengsheng Inventor after: Guo Weicheng Inventor after: Huang Xiaoxia Inventor after: Jia Zhongxin Inventor after: Huo Caixia Inventor after: Meng Xianhui Inventor before: Che Fengsheng Inventor before: Guo Weicheng Inventor before: Jia Zhongxin Inventor before: Huo Caixia Inventor before: Meng Xianhui |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: INVENTOR; FROM: CHE FENGSHENG GUO WEICHENG JIA ZHONGXIN HUO CAIXIA MENG XIANHUI TO: CHE FENGSHENG GUO WEICHENG HUANG XIAOXIA JIA ZHONGXIN HUO CAIXIA MENG XIANHUI |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20211028 Address after: 134000 No. 68, Xiangjiang Road, Meihekou City, Tonghua City, Jilin Province Patentee after: Jilin Zhen Ao Pharmaceutical Co.,Ltd. Patentee after: BEIJING SIHUAN PHARMACEUTICAL Co.,Ltd. Patentee after: HAINAN SIHUAN PHARMACEUTICAL Co.,Ltd. Address before: 101114 Beijing city Tongzhou District three Airport Hospital Beijing Sihuan Pharmaceutical Co. Ltd. Patentee before: BEIJING SIHUAN PHARMACEUTICAL Co.,Ltd. Patentee before: HAINAN SIHUAN PHARMACEUTICAL Co.,Ltd. |