CN103127121A - Rasagiline/folic acid compound medicine combination and purpose thereof - Google Patents
Rasagiline/folic acid compound medicine combination and purpose thereof Download PDFInfo
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- CN103127121A CN103127121A CN 201110397772 CN201110397772A CN103127121A CN 103127121 A CN103127121 A CN 103127121A CN 201110397772 CN201110397772 CN 201110397772 CN 201110397772 A CN201110397772 A CN 201110397772A CN 103127121 A CN103127121 A CN 103127121A
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Abstract
The invention relates to a rasagiline/folic acid compound medicine combination and a purpose thereof, and belongs to the technical field of pharmacy. The medicine combination comprises the rasagiline with an officinal dose, the folic acid compounds with an officinal dose, and a carrier which can be accepted in pharmacy. The dose of the rasagiline is 0.5-2 mg, and the dose of the folic acid compounds is 0.2-1.6 mg. The medicine combination has the advantages that through synergistic effect of multiple target points, curative effect on the Parkinson's disease is improved, life quality of a patient is improved, through a homocysteine (Hcy) target point, cerebral apoplexy of the patient with the Parkinson's disease can be effectively prevented, occurring risk of the cerebral apoplexy can be effectively lowered, and in addition, the patient can conveniently take medicine.
Description
Technical field
The present invention relates to a kind of medical composition and its use of rasagiline/folacin compound, belong to pharmaceutical technology.
Background technology
Parkinson disease (Parkinson ' s Disease, PD) be the handicapped chronic progressive disease of a kind of central nervous system's extrapyramidal system.The main pathological manifestations of PD is dopamine (DA) neuronal degeneration in black substance, and central neurotransmitter DA content reduces, and the degree of exhaustion of DA is consistent with the order of severity of PD; Simultaneously also can be with the abnormal and dysequilibrium of the various neurotransmitters such as acetylcholine (Ach), 5-hydroxy tryptamine (5-HT), norepinephrine (NE), γ-aminobutyric acid and neuropeptide, thereby cause a series of clinical symptoms, as muscular tremor, stiff, posture obstacle, dyskinesia etc.It is reported, the existing PD patient of the U.S. approximately 1,500,000, are used for the treatment of the expense of PD every year up to 10,000,000,000 dollars.China PD patient total number of persons has reached 1,720,000, crowd PD prevalence nearly 1% more than 55 years old at present.PD is a kind of lifelong participation disease, in case ill need lifelong treatment, Drug therapy is still present topmost method, and common drug comprises:
(1) anticholinergic: mainly contain benzhexol, usage 1～2mg, every day 3 times.Also have in addition kemadrin, benztropine, scopolamine, cycrimine and BIPERIDEN.Mainly be applicable to the patient that trembles, the patient of atremia generally need not, especially the gerontal patient is cautious use of, narrow cleft glaucoma and prostate hyperplasia patient forbidding.
(2) amantadine: usage 50～100mg, every day 2～3 times, last should be taken before 4 o'clock in the afternoon.To less moving, tetanic, trembling all is improved effect, may be helpful to companion's unusual fluctuation disease patient.Renal insufficiency, epilepsy, serious gastric ulcer, hepatopath are cautious use of, women breast-feeding their children's forbidding.
(3) Benserazide (benserazide levodopa, carbidopa levodopa): predose 62.5～125mg, every day 2～3 times, according to the state of an illness and cumulative dosage to satisfactory effect and the optimal dose when side effect not occurring keep treatment, 1h or took medicine in 1 and a half hours after the meal before the meal.The activeness digestive tract ulcer person be cautious use of, narrow cleft glaucoma, psychotic's forbidding.
(4) DR agonist: mostly praising highly non-Ergota class DR agonist at present is choice drug, is particularly useful for the young patient course of disease initial stage.Stimulate because the long half-lift of this class, preparation can avoid that striatum postsynaptic membrane DR is produced " pulse " sample, thus the generation of prevention or minimizing motor complication.Agonist all should be from low dose, and cumulative dosage is to obtaining satisfactory effect till side effect not occurring.Side effect is similar to Benserazide, and difference is that symptom fluctuation and unusual fluctuation disease incidence rate are low, and postural hypotension and mental symptom incidence rate are higher.The DR agonist has 2 types, and the Ergota class comprises bromocriptine, pergolide, α-dihydroergo cryptine(DCS90), cabergoline and lisuride; Non-Ergota class comprises pramipexole (pramipexole), ropinirole, piribedil, rotigotine and apomorphine.Ergota class DR agonist can cause valve disorder and visceral pleura fibrosis, now do not advocated to use, and pergolide is domestic inactive.Find not yet that at present non-Ergota class DR agonist has this side effect.The non-Ergota class DR agonist of present domestic listing: 1. piribedil slow releasing tablet: predose 50mg, easily produces the side reaction patient and can change 25mg at every day 1 time, every day 2 times, the 2nd week increased to 50mg, every day 2 times, effective dose 150mg/d, minutes 3 times are oral, and maximum is no more than 250mg/d; 2. pramipexole: predose 0.125mg, increase weekly 0.125mg every day 3 times (indivedual easily produce the untoward reaction patients be 1～2 time), every day 3 times, general effective dose 0.50～0.75mg, every day 3 times, maximum is no more than 4.5mg/d.The Ergota class DR agonist of domestic listing: 1. bromocriptine: 0.625mg, increase 0.625mg every 5d every day 1 time, effective dose 3.75～15.0mg/d, minutes 3 times are oral; 2. α-dihydroergo cryptine(DCS90): 2.5mg increases 2.5mg every 5d every day 2 times, effective dose 30～50mg/d, and minutes 3 times are oral.
(5) MAO-B inhibitor: selegiline and rasagiline are arranged at present.The usage of selegiline is 2.5～5.0mg, every day 2 times, should be early, take noon, and not between the lights or use in order to avoid cause insomnia evening, or share (DATATOP scheme) with vitamin E 2000IU; The usage of rasagiline is 1mg, and every day 1 time, take morning.Absorption, effect, the safety of novel form Zydis selegiline (oral mucosa disintegrating agent) all are better than the selegiline standard film, and usage is 1.25～2.50mg/d.Rasagiline be used for 1 time on the 1st single therapy Early Parkinson's disease and as, late period parkinson disease levodopa therapy additional medication, recommended dose is 1mg.
(6) COMT inhibitor: grace tolcapone or tolcapone.Each 100～the 200mg of grace tolcapone takes number of times identical with Benserazide, if it is more to take the Benserazide number of times every day, also can be less than the number of times of taking of Benserazide, and the grace tolcapone needs and the same clothes of Benserazide, and is alone invalid.The each 100mg of tolcapone, every day 3 times, first dose takes with Benserazide is same, and after this interval 6h takes, can be alone, every day, maximal dose was 600mg.Side effect has diarrhoea, headache, hyperhidrosis, xerostomia, aminotransferase rising, stomachache, urine discoloration Huang etc.Tolcapone might cause liver function injury, must tight monitoring liver function, and especially medication 3 months.If treatment might prevent or the generation of lag motion complication to the first-selected Stalevo of untreated early stage patient (by grace tolcapone-levodopa-carbidiopa compound formulation).
Homocysteine (Homocysteine, Hcy) is a kind of sulfur-containing amino acid, is an important intermediate of methionine metabolism in body.Generation and the metabolism disequilibrium of Hcy, cause hyperhomocysteinemiainjury under the various factors such as heredity, age, nutrition, disease.Nineteen ninety-five, at first Allain etc. have reported that parkinson disease (Parkinson ' s disease, PD) patient has higher plasma Hcy level.Hcy promotion PD's is machine-processed as follows:
(1) promote the be overexcited neurotoxicity of N-methyl D-sky (door) winter propylhomoserin receptor (NMDA) and metabotropic glutamate receptors (mGluR) enhancing glutamic acid of the cytotoxicity of excitatory toxicity and calcium: Hcy, and this toxicity of Hcy generation can be weakened by the metabotropic glutamate receptor inhibitor.The oxidative damage that high Hcy causes comes from intracellular calcium [Ca
2+] rising of i level.Hcy causes [Ca in cultured cell by nmda receptor
2+] rising of i level, the calcium ion inhibitor can weaken this increasing.Experiment shows, the Hcy of 0.5mmol/L just can make endochylema [Ca
2+] i increases and have an obvious dose-effect relationship.
(2) accelerating oxidation stress: Upchurch etc. 1997 report Hcy damage glutathione peroxidase active and reduce vitamin A, vitamin C and vitamin E in tissue.N-acetyl-L-cysteine (NAC), vitamin C and vitamin E can reduce the non-neuronal apoptosis that Hcy mediates by removing hydroperoxides.Uric acid fully inhibited oxidation stress, and 3-AB only can play partial action.
(3) promote energy expenditure: Streck etc. to inject the people that takes the photograph that Hcy can reduce tricarboxylic acid cycle product and glucose significantly to animal, affect the activity of succinate dehydrogenase, cytochrome C oxidase.The DNA break that the cultivation neuron that Hcy processed causes in order to repair it finally consumes neuronic ATP and stores.Therefore, in the PD chronic phase, gently accelerate the consumption of the ATP that reduced in old brain to the high Hcy of moderate, thereby aggravate disease.
(4) lesion wire mitochondria function: the measurement of mitochondrial membrane potential discloses the depolarization that Hcy has aggravated film, and uric acid and 3-AB be the at utmost depolarization of the mitochondrial membrane that jointly causes of ground resistance Hcy processed and rotenone and ferrum all.The level of mitochondrial oxidation product increases in rotenone and ferrum cultured cells, and increases more obviously when having Hcy, and above variation has finally suppressed the activity of composite I in the mitochondrial respiratory chain, ATP dyssynthesis and cause cytopathy dead.
(5) accelerate apoptosis: high Hcy causes that by activating Caspase (Caspase) and p53 the reduction of mitochondrion transmembrane voltage causes apoptosis.Experiment discovery 3-AB can suppress the p53 increase that high Hcy induces significantly, stream in calcium, and active chalcogen, the reduction of the active increase of caspase and mitochondrion transmembrane voltage shields to apoptosis.
Summary of the invention
The present invention provides a kind of and obviously is being better than the pharmaceutical composition of rasagiline aspect the anti-parkinson curative effect in order to make up the deficiency of rasagiline in the treatment parkinson disease.
For achieving the above object, the present invention is by the following technical solutions:
A kind of pharmaceutical composition of rasagiline/folacin compound contains the rasagiline of pharmaceutical dosage, acceptable carrier on the folacin compound of pharmaceutical dosage and pharmaceutics.
The dosage range of above-mentioned " pharmaceutical dosage " main reference " Chinese treatment of Parkinson disease guide (second edition) " and each package insert regulation.
The dosage of described rasagiline is 0.5～2.0mg.Described folacin compound is one or more in folic acid, calcium folinate or levoleucovorin calcium, and dosage is 0.2～1.6mg.
This research finds, when rasagiline/folacin compound coupling, the preventive and therapeutic effect that MPTP is caused Parkinson disease mice obviously is better than using rasagiline.
Therefore, the invention provides pharmaceutical composition that the rasagiline of above-mentioned pharmaceutical dosage/folacin compound forms for the preparation of prevention, treat or delay the parkinson disease medicine in purposes.
The dosage form of pharmaceutical composition of the present invention is conventional tablet, conventional capsule, soft capsule, granule, slow releasing tablet, sublingual lozenge, oral cavity quick disintegrating slice, dispersible tablet, enteric coatel tablets, enteric coated capsule, delayed-release tablet, regularly/position releasing piece, slow releasing capsule, controlled release capsule, contain the capsule of micropill or small pieces, contain pH dependent form capsule or the oral liquid of micropill or small pieces.
Also contain the pharmaceutics acceptable carrier in this pharmaceutical composition, can be made into common oral preparation, comprise conventional tablet, conventional capsule etc., when making tablet, described pharmaceutically acceptable carrier includes excipient and the adjuvant that helps reactive compound is mixed with pharmaceutical formulation, compositions as one or more materials of starch, microcrystalline Cellulose, inorganic salts, sucrose, dextrin, lactose, Icing Sugar, glucose, sodium chloride, cysteine, citric acid and sodium sulfite etc. belongs to this area general knowledge.
Also contain the pharmaceutics acceptable carrier in this pharmaceutical composition, can be made into slow releasing tablet, comprise excipient and adjuvant etc.described excipient and adjuvant have comprised that the adjuvant of slow releasing function is solubility/insoluble salt and/or other adjuvant that plays slow releasing function of hypromellose and/or ethyl cellulose and/or polyacrylic resin class and/or polycarboxy ethene and/or alginic acid, the hypromellose employing includes the extensive stock of hydroxypropyl methylcellulose (HPMC) such as U.S. many elegant (Methocel) of all size, ethyl cellulose adopts the extensive stock that includes ethyl cellulose (EC), the polyacrylic resin class adopts and includes polyacrylic resin II, the acrylic resin of III class or analog such as all size (Eudragit).Above-mentioned adjuvant is porogen, binding agent, lubricant, emulsifying agent, membrane material, solvent or other adjuvant, and porogen can adopt sucrose, mannitol, starch, Pulvis Talci, silicon dioxide etc.; Binding agent can adopt polyvinylpyrrolidone, hypromellose etc.; Wetting agent can adopt the ethanol-water solution of water, dehydrated alcohol, various concentration; Lubricant can adopt stearic acid, magnesium stearate, Pulvis Talci, starch, paraffin etc.; Solubilizing agent can be adopted tartaric acid, citric acid etc.; Emulsifying agent can adopt span80 span85 etc.; Membrane material can adopt polyvinyl alcohol, hydroxyl methylcellulose, hydroxyl second fibre object, hymetellose, methylcellulose etc.; Foaming agent can adopt basic magnesium carbonate, sodium bicarbonate etc.; Bleach activator can adopt hexadecanol, octadecanol, Cera Flava etc.; Solvent can adopt dehydrated alcohol, ethanol, water etc.
Also contain the pharmaceutics acceptable carrier in this pharmaceutical composition, can be made into controlled release tablet, comprise that active medicine has reached the adjuvant of controlled release effect.The above-mentioned adjuvant that plays the controlled release effect is polyoxyethylene and/or hypromellose and/or ethyl cellulose and/or sodium chloride and/or lactose and/or mannitol and/or fructose and/or glucose and/or sucrose and/or low-substituted hydroxypropyl cellulose and/or cross-linking sodium carboxymethyl cellulose and/or crospolyvinylpyrrolidone and/or cellulose acetate.Above-mentioned adjuvant is pharmaceutical carrier, expanding material, permeation-promoter, solubilizing agent, binding agent, wetting agent, lubricant, coloring agent, porogen, membrane material, antiplastering aid, plasticizer, lucifuge agent, solvent.Pharmaceutical carrier, expanding material can adopt polyoxyethylene, hypromellose, ethyl cellulose, Glyceryl Behenate class etc.; Permeation-promoter can adopt sodium chloride, lactose, mannitol, fructose, glucose, sucrose etc.; Solubilizing agent can be adopted sodium lauryl sulphate or poloxamer etc.; Binding agent can adopt polyvinylpyrrolidone, hypromellose etc.; Wetting agent can adopt the ethanol-water solution of water, dehydrated alcohol, various concentration; Lubricant can adopt stearic acid, magnesium stearate, Pulvis Talci, starch, paraffin etc.; Coloring agent can adopt iron oxide red, iron oxide yellow etc.; Porogen can adopt sucrose, mannitol, Polyethylene Glycol, titanium dioxide, Pulvis Talci, silicon dioxide etc.; Membrane material can adopt cellulose acetate, ethyl cellulose etc.; Solvent can adopt acetone, dehydrated alcohol, ethanol, water etc.
Also contain the pharmaceutics acceptable carrier in this pharmaceutical composition, can be made into sublingual lozenge, oral cavity quick disintegrating slice or dispersible tablet etc., comprise excipient and adjuvant etc.Described excipient and adjuvant have low substituted hydroxy-propyl methylcellulose, microcrystalline Cellulose, carboxymethyl starch sodium, cross-linked carboxymethyl cellulose sodium, crospolyvinylpyrrolidone, processing agar and mannitol, lactose etc.
also contain the pharmaceutics acceptable carrier in this pharmaceutical composition, can be made into enteric coatel tablets or enteric coated capsule etc., comprise excipient and adjuvant etc., described excipient and adjuvant have starch, microcrystalline Cellulose, inorganic salts, hydroxypropyl emthylcellulose, ethyl cellulose, the polyacrylic resin class, polycarboxy ethene, the solubility of alginic acid/insoluble salt, octadecanol, stearic acid, sucrose, dextrin, lactose, Icing Sugar, glucose, sodium chloride, cysteine, the compositions of one or more materials of citric acid and sodium sulfite etc., enteric-coating material comprises: Lac, CAP, crylic acid resin (as Eudragit L and S type etc.), the polyvinyl acetate phthalic acid ester, Hydroxypropyl Methyl Cellulose Phthalate, succinic acid acetic acid hydroxypropyl methylcellulose, and plasticizer is (as diethyl phthalate, Polyethylene Glycol, propylene glycol, glycerol triacetate, dimethyl phthalate, triethyl citrate, tributyl citrate, CitroflexA-2, the acetylated monoglycerides of Oleum Ricini and percentage etc.) with the various medicaments adjuvant such as porogen (as PEG6000 etc.).
also contain the pharmaceutics acceptable carrier in this pharmaceutical composition, can be made into delayed-release tablet or timing (position) releasing piece, comprise excipient and adjuvant, described excipient and adjuvant have starch, microcrystalline Cellulose, inorganic salts, hydroxypropyl emthylcellulose, ethyl cellulose, the polyacrylic resin class, polycarboxy ethene, the solubility of alginic acid/insoluble salt, octadecanol, stearic acid, sucrose, dextrin, lactose, Icing Sugar, glucose, sodium chloride, cysteine, the compositions of one or more materials of citric acid and sodium sulfite etc., the coating material of described delayed release or regularly (position) release comprises: Lac, CAP, ethyl cellulose, hydroxypropyl emthylcellulose, hydroxypropyl cellulose, crylic acid resin (as Eudragit L and S type etc.), the polyvinyl acetate phthalic acid ester, Hydroxypropyl Methyl Cellulose Phthalate, succinic acid acetic acid hydroxypropyl methylcellulose, hydroxypropylmethylcellulose acetate methylcellulose phthalate ester, and plasticizer is (as diethyl phthalate, Polyethylene Glycol, propylene glycol, glycerol triacetate, dimethyl phthalate, triethyl citrate, tributyl citrate, CitroflexA-2, the acetylated monoglycerides of Oleum Ricini and percentage etc.) with the various medicaments adjuvant such as porogen (as PEG6000 etc.).
also contain the pharmaceutics acceptable carrier in this pharmaceutical composition, can be made into slow releasing capsule, controlled release capsule contains the capsule of micropill or small pieces, contains the PH dependent form capsule of micropill or small pieces etc., comprises excipient and adjuvant, and described excipient and adjuvant have starch, microcrystalline Cellulose, inorganic salts, hydroxypropyl emthylcellulose, ethyl cellulose, the polyacrylic resin class, polycarboxy ethene, the solubility of alginic acid/insoluble salt, octadecanol, stearic acid, sucrose, dextrin, lactose, Icing Sugar, glucose, sodium chloride, cysteine, the compositions of one or more materials of citric acid and sodium sulfite etc., coating material comprises Lac, cellulose acetate, CAP, ethyl cellulose, hydroxypropyl emthylcellulose, hydroxypropyl cellulose, crylic acid resin (as Eudragit series), the polyvinyl acetate phthalic acid ester, Hydroxypropyl Methyl Cellulose Phthalate, succinic acid acetic acid hydroxypropyl methylcellulose, hydroxypropylmethylcellulose acetate methylcellulose phthalate ester, glyceryl monostearate, and plasticizer is (as diethyl phthalate, Polyethylene Glycol, propylene glycol, glycerol triacetate, dimethyl phthalate, triethyl citrate, tributyl citrate, CitroflexA-2, acetylated monoglycerides of Oleum Ricini and percentage etc.) with the various medicaments adjuvant such as porogen (as PEG6000 etc.).
Also contain the pharmaceutics acceptable carrier in this pharmaceutical composition, can be made into the dosage forms such as granule, oral liquid.During the granulation agent, described diluent has starch, sucrose or lactose etc., and disintegrating agent has starch, cellulose derivative etc., and binding agent has water etc.
The invention has the beneficial effects as follows: 1. can effectively work in coordination with anti-parkinson when rasagiline and folacin compound coupling, increase rasagiline anti-parkinson curative effect, overcome the low shortcoming of its drug action; 2. this pharmaceutical composition still can effectively prevent and reduce the risk of the generation of disturbances in patients with Parkinson disease apoplexy by homocysteine (Hcy) target spot; 3. in addition, the patient is taken medicine conveniently.
Below in conjunction with embodiment, the invention will be further described.
The specific embodiment
The preparation of embodiment 1. tablets
Prescription:
Preparation technology:
(1) getting the rasagiline of recipe quantity and folic acid crosses after 100 mesh sieves standby by equivalent incremental method mix homogeneously;
(2) other adjuvant is crossed respectively after 100 mesh sieves 75 ℃ of dryings 2 hours;
(3) press after the starch, microcrystalline Cellulose, CMS.Na mixing of recipe quantity again and mixed crude drug equivalent incremental method mix homogeneously;
(4) add binding agent soft material processed in right amount, 24 mesh sieves are granulated, 20 mesh sieve granulate, 40～75 ℃ of dryings.
(5) dry grain adds appropriate magnesium stearate mixing, tabletting after assay, packing.
Every day 1 time, each 1.
The preparation of embodiment 2. capsules
Prescription:
Preparation technology:
By the prescription proportioning, get lactose, microcrystalline Cellulose, starch, carboxymethylstach sodium in about 100 ℃ dry approximately 2 hours respectively, 100 mesh sieves; After crude drug is crossed 100 mesh sieves, increase progressively mixing with above-mentioned adjuvant by equivalent, the capsule fill.
Every day 1 time, each 1.
The preparation of embodiment 3. slow releasing tablet
Prescription:
Preparation technology:
By the prescription proportioning, with crude drug and hypromellose mixing, citric acid is dissolved in ethanol makes soft material as wetting agent, granulation, and drying, granulate adds the magnesium stearate mixing, tabletting and get final product.
The next day 1 time, each 1.
The preparation of embodiment 4. granules
Preparation technology:
With crude drug and the abundant mixing of proper starch, add appropriate water soft material processed.With soft material with mechanical presses by screen cloth wet granular processed, box-type drying granule, granulate and classification.
Every day 1 time, each 1 bag.
Test case 1. folic acid strengthen the effect of rasagiline anti-parkinson
(1) animal model and grouping administration
Mice is divided into 4 groups at random, 12 every group, is respectively blank group, model control group, rasagiline group (1.0mg/kg) and rasagiline/folic acid group (1.0/0.1mg/kg).The continuous gastric infusion 30d of mice, 1h lumbar injection MPTP 30mg/kg (matched group gives isopyknic normal saline) before the 27th day beginning gastric infusion, continuous 4d, after last 1 administration, 1d carries out behavioristics's index test.
(2) behavioristics's index test
1. autonomic activities experiment: use XZ-4 type mice autonomic activities instrument to measure spontaneous activity in mice and numeration, measure the movable number of times in every mice 5min, carry out statistical procedures.
2. cylinder experiment: use the cylinder behavior performance of SD-2 type mice cylinder instrument test mice.Mice is placed on the cylinder of cylinder instrument, rotating speed 35r/min is set, the test mice begins to rotate to time of leaving cylinder as mouse movement incubation period from cylinder.
(3) experimental result
1. autonomic activities experiment: the MPTP model control group is compared movable number of times and is obviously reduced (P＜0.01) with the blank group, rasagiline group (1.0mg/kg) and rasagiline/folic acid group (1.0/0.1mg/kg) all can obviously increase its movable number of times (P＜0.01), but rasagiline/folic acid group successful is better than rasagiline group (table 1).
The impact of table 1. on the mice autonomic activities
Compare with the blank group
*P＜0.01; Compare with model control group
##P＜0.01; Compare with the rasagiline group
△P＜0.05
2. cylinder experiment: the MPTP model control group is compared with the blank group, ML obviously shortens (P＜0.01), rasagiline group (1.0mg/kg) and rasagiline/folic acid group (1.0/0.1mg/kg) all can obviously increase its ML (P＜0.01), but rasagiline/folic acid group successful is better than rasagiline group (table 2).
Table 2. is on the preclinical impact of mouse movement
Compare with the blank group
*P＜0.01; Compare with model control group
##P＜0.01; Compare with the rasagiline group
△P＜0.05
(4) experiment conclusion
After rasagiline and folic acid were united use, no matter from autonomic activities experiment or cylinder experiment, result showed that all folic acid has strengthened the curative effect of rasagiline anti-parkinson (P＜0.05) significantly, and this is the main vertical topic foundation of this compositions just.
Claims (5)
1. the pharmaceutical composition of a rasagiline/folacin compound, is characterized in that: contain the rasagiline of pharmaceutical dosage, acceptable carrier on the folacin compound of pharmaceutical dosage and pharmaceutics.
2. pharmaceutical composition according to claim 1, it is characterized in that: the dosage of described rasagiline is 0.5～2.0mg.
3. pharmaceutical composition according to claim 1, it is characterized in that: described folacin compound is one or more in folic acid, calcium folinate or levoleucovorin calcium, dosage is 0.2～1.6mg.
4. arbitrary described pharmaceutical composition according to claim 1～3 is characterized in that: the dosage form of described pharmaceutical composition is conventional tablet, conventional capsule, soft capsule, granule, slow releasing tablet, sublingual lozenge, oral cavity quick disintegrating slice, dispersible tablet, enteric coatel tablets, enteric coated capsule, delayed-release tablet, regularly/position releasing piece, slow releasing capsule, controlled release capsule, contain the capsule of micropill or small pieces, contain pH dependent form capsule or the oral liquid of micropill or small pieces.
according to claim 1～3 arbitrary described pharmaceutical composition for the preparation of prevention, treat or delay the parkinson disease medicine in purposes.
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| CN 201110397772 CN103127121A (en) | 2011-12-02 | 2011-12-02 | Rasagiline/folic acid compound medicine combination and purpose thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104473942A (en) * | 2014-12-12 | 2015-04-01 | 青岛大学 | Medicine composition with resistance to Parkinson disease |
| WO2018223895A1 (en) * | 2017-06-07 | 2018-12-13 | 广州帝奇医药技术有限公司 | Long-acting sustained-release preparation of drug against parkinson's disease and preparation method thereof |
-
2011
- 2011-12-02 CN CN 201110397772 patent/CN103127121A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104473942A (en) * | 2014-12-12 | 2015-04-01 | 青岛大学 | Medicine composition with resistance to Parkinson disease |
| WO2018223895A1 (en) * | 2017-06-07 | 2018-12-13 | 广州帝奇医药技术有限公司 | Long-acting sustained-release preparation of drug against parkinson's disease and preparation method thereof |
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Addressee: Suzhou Famo Biological Technology Co., Ltd. Document name: Notification that Application Deemed to be Withdrawn |
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Application publication date: 20130605 |