CN106309417A - Pharmaceutical composition for treating diseases related to Parkinson's diseases - Google Patents
Pharmaceutical composition for treating diseases related to Parkinson's diseases Download PDFInfo
- Publication number
- CN106309417A CN106309417A CN201610712574.0A CN201610712574A CN106309417A CN 106309417 A CN106309417 A CN 106309417A CN 201610712574 A CN201610712574 A CN 201610712574A CN 106309417 A CN106309417 A CN 106309417A
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- CN
- China
- Prior art keywords
- fanselin
- fce
- methanesulfonic acid
- tartaric acid
- parkinson
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- 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.)
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4468—Non condensed piperidines, e.g. piperocaine having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
Abstract
The invention relates to the field of a medical technology and particularly relates to a composition including Safinamide Mesylate and Pimavanserin Tartrate. The composition can be used for treating Parkinson's diseases and mental diseases related to Parkinson's diseases.
Description
Technical field
The present invention relates to pharmaceutical technology field, more particularly to a kind of methanesulfonic acid FCE-26743A and tartaric acid Mo Fanselin
Compositions, can be used for treating parkinson disease and the mental sickness relevant to parkinson disease.
Background technology
Methanesulfonic acid FCE-26743A (safinamide mesylate) is by being devoted to exploitation central nervous system disease medicine
Drugmaker's knob grand (Newron) and marketing partner thereof praise the exploitation of nation (Zambon) joint research and development.Methanesulfonic acid FCE-26743A is
A kind of sodium channel and calcium channel complex blocking agent, release glutamate, be again selectivity MAO-B inhibitor, can selectivity impact put
Electricity abnormal neuron and do not change the activity of normal neurons.
Methanesulfonic acid FCE-26743A has two advantages compared with its competing product.First, it has high special to MAO-B
Property, therefore can limit or eliminate dietary restrictions (dietary restrictions), this in other similar medicine still
It it is a problem the biggest；Second, methanesulfonic acid FCE-26743A has double action mechanism, in addition to can suppressing MAO-B, also has suppression
The additional function of glutamic neuron (glutamate release), in theory, this may produce neuroprotective, compares
Providing only the situation of symptomatic treatment at present, it more can meet the unmet demand of the key on market, current MAO-B suppression
Agent, rasagiline particularly, also been proposed and there is neuroprotective, but clinical data can not fully support this
Assume.Therefore, methanesulfonic acid FCE-26743A is likely to become the medicine more favored by doctor.In any case, doctor is to this medicine
Thing medicine is placed high hopes, it is believed that it can slow down the progress of disease.
Tartaric acid Mo Fanselin (pimavanserin tartrate) is to be developed by ACADIA drugmaker of the U.S. to open
, played a role by the serotonin 5-hydroxy tryptamine 2A receptor on blocking-up neopallium, think of when neopallium is for being responsible for sensation, regaining consciousness
Dimension and the brain area of language, also relevant with visual hallucination and illusion.Tartaric acid Mo Fanselin can be used for treating parkinson disease
Relevant mental symptom, this indication has been obtained for the granted listing of accreditation of FDA at present；Can also be used for and alzheimer disease
Relevant mental sickness, this indication is in second phase clinical investigation phase；It addition, can be additionally used in treatment schizophrenia etc..This
Product will become the first medicine being specifically designed to parkinson disease related psychiatric conditions in the whole world.
Parkinson disease (Parkinson's disease, PD) are a kind of common nervous system degeneration diseases.Clinical main
Show as the motor system symptoms such as static tremor, bradykinesia, myotonia and posture abnormal gait, can merge simultaneously hallucination,
The psychotic symptoms such as vain hope, depression.These neuropsychic symptoms not only health to patient becomes grievous injury, and gives patient
Psychology brings the impact that can not be ignored, and makes the quality of life of patient decline further, thus increases the weight of family and burden on society.Its
In, it has been reported that, parkinson merge depressed sickness rate and are easier to patients complicated with depression from 2.7%-90%, female patient.Cause
This, the treatment of PD patient mental's symptom can not be ignored.
At present, merging the medicine of mental sickness the most temporarily without being specifically designed for parkinson, in this research, methanesulfonic acid is husky
Fragrant amide is a kind of anti-Parkinson new drug with multiple mechanism of action, and tartaric acid Mo Fanselin is the treatment handkerchief of a kind of novelty
The medicine of the gloomy related psychiatric conditions of gold, both share, and will provide effectively for the concurrent psychiatric patient of the most numerous parkinson
Medicine.
Summary of the invention
It is an object of the invention to provide a kind of methanesulfonic acid FCE-26743A and tartaric acid Mo Fanselin compositions, solve handkerchief
Jin Sen merges the mental sickness problem currently without special for treating medicine.Parkinsonian is in the process of drug administration, generally
There will be, hallucination, vain hope, the psychotic symptoms such as depressed, had a strong impact on quality of life and health status.Methanesulfonic acid FCE-26743A
With tartaric acid Mo Fanselin use in conjunction, parkinson symptom can be improved, the psychiatric disorders of patient can be alleviated again.
The effective dose that each preparation unit of said composition contains methanesulfonic acid FCE-26743A is 25mg～200mg, containing wine
The effective content of a stone acid Mo Fanselin is 10～60mg.The methanesulfonic acid FCE-26743A that the most each preparation unit contains is
50mg, is 20mg containing tartaric acid Mo Fanselin.For a person skilled in the art, dosage rate is can be according to disease
Situation condition, determines after the combined factors evaluation such as age.
Said composition is used for treating parkinson and parkinson relevant disease, and developable dosage form has tablet, capsule, dispersion
Sheet, slow releasing tablet, the dosage form such as oral administration solution, preferred tablet, dispersible tablet.
The above-mentioned tablet preferred adjuvant of use: polyvidone (PVP), microcrystalline Cellulose, carboxymethyl starch sodium, lactose hydrous,
Magnesium stearate, hypromellose, Polyethylene Glycol, mannitol, pregelatinized Starch, hand over sodium carboxymethyl cellulose, hypromellose
Element, Opadry, one or more in Brazil wax.
A kind of methanesulfonic acid FCE-26743A of present invention offer and tartaric acid Mo Fanselin compositions, wherein methanesulfonic acid sand is fragrant
Amide is a kind of sodium channel and calcium channel complex blocking agent, release glutamate, is again selectivity MAO-B inhibitor, can selectivity
Affecting and discharge abnormal neuron and do not change the activity of normal neurons, side effect is little.Tartaric acid Mo Fanselin passes through
Block the serotonin 5-hydroxy tryptamine 2A receptor on neopallium and play a role, neopallium for be responsible for sensation, clear-headed time thinking and
The brain area of language, also relevant with visual hallucination and illusion.Said composition can provide more preferable medication to select to clinical patients,
Fill up clinical blank.
Detailed description of the invention
In order to be better understood from the present invention, below by the description to invention preferred embodiment, explain in detail this
Bright, but limit the present invention the most in any form.
The preparation of embodiment 1 tablet
Preparation technology: methanesulfonic acid FCE-26743A, tartaric acid Mo Fanselin and polyvinylpolypyrrolidone, microcrystalline Cellulose, hydroxypropyl
Methylcellulose mix homogeneously, adds appropriate purified water and makes soft material, then crosses 16 mesh sieves and pelletizes.Wet granular is dried at 60 DEG C,
Dry granule crosses 16 mesh sieve granulate, sifts out the fine powder in dry granular, mixes with magnesium stearate, mixes with dry granule, tabletting, both the most again
?.Methanesulfonic acid FCE-26743A and tartaric acid Mo Fanselin compositions are for the psychotic clinical research of disturbances in patients with Parkinson disease:
Object of study: this test totally 207 example patients enter people's screening, and participation randomized grouping completes baseline estimate, and person is total to
207 examples, errorless at lose-lose personal data blind review, and open-blind after lock database, enter people and treat patient 207 example of phase, first sulphur
Acid FCE-26743A and tartaric acid Mo Fanselin combination group (A group) 69 examples, methanesulfonic acid FCE-26743A group (B group) 69 examples, tartaric acid
Mo Fanselin (C group) 69 examples.Baseline period M-F be the mean age of 140:67, A group be (63.95 ± 9.84) year, flat
All individual month of courses of disease (63.29 ± 50.76)；Year mean age (65.64 ± 8.16) of B group, average course of disease (65.26 ± 48.45)
Individual month, year mean age (63.64 ± 9.16) of C group, individual month of average course of disease (64.26 ± 45.45).Between baseline condition two groups poor
Different equal not statistically significant.
Experiment packet: methanesulfonic acid FCE-26743A and tartaric acid Mo Fanselin combination group (A group), methanesulfonic acid FCE-26743A group
(B group), tartaric acid Mo Fanselin (C group).
Dosage regimen: A group: 50mg/20mg compositions, tablet；B group: 50mg tablet；C group: 20mg tablet.Medicining cycle 4
Week, it is not necessary to adjust dosage.Add with A, B, C group medicine on the basis of the medicine that patient previously takes.
Efficacy assessment standard: leading indicator is the motion inspection of unified parkinson disease rating scale the IIIth part (UPDRS III)
Look into the change of overall score versus baseline；The change of the daily life active ability overall score versus baseline of the IIth part.Secondary finger
It is designated as UPDRS I (spirit, behavior and emotion) and the change of IV (complication for the treatment of) overall score versus baseline；UPDRS II to IV
The ratio of the patient of the change 30% of middle any portion total score versus baseline；The change of levodopa daily dosage versus baseline；
To share levodopa and occur the patient of " on-off phenomenon ", based on Patients Diary, evaluate time "ON" phase, the "Off" phase is when accounting for awakening
Between percent and the overall evaluation of clinical efficacy.
Statistical analysis: this research efficacy analysis is by Intentionality treatment (IT) population analysis and meets therapeutic scheme (PP) people
Cluster analysis.The Baseline Data of study population carries out corresponding descriptive statistic amount (average of continuous variable and the frequency of classified variable
Number distribution) calculating.Curative effect is to be analyzed from baseline to each observation period, the change of efficacy evaluation index by comparing two groups.
With treatment group and research center as the factor, the change before and after two groups of treatments is carried out variance analysis and covariance analysis.
Use the model getting rid of research center and treatment reciprocal effect that therapeutic effect is carried out statistical test.By major variable
The equivalent boundary of UPDRS II, III overall score is set to 1.0 and 2.0 respectively, carries out non-bad effect and analyzes.By X 2 test to two groups
Between the percent of effective patient compare analysis.Patient's number of the abnormal laboratory examination results occurred after confirming treatment
With untoward reaction relative frequency, and the difference to two groups is accurately checked to compare analysis with Fisher.
Interpretation of result: in Intentionality treatment crowd, compare with baseline after treating 4 weeks, the UPDRS III of A group, B group and C group is total
Scoring average declines 11.60 points, 10.01 points and 9.86 points respectively；UPDRS II overall score average decline respectively 3.79 points, 2.22
Divide and 2.60 points；A group is excellent imitates in B group and C group.Experimenter's ratio, researcher in UPDRS II～IV overall score change >=30%
Overall clinical evaluates the aspects such as the onset time with medicine, and A group is superior to B group and C group (P < 0.05).
The comparison of UPDRS scoring before and after ABC tri-groups treatment
Note: compare with baseline,*P < 0.01,#P < 0.05: do not do.
Claims (4)
1. methanesulfonic acid FCE-26743A and a tartaric acid Mo Fanselin compositions, is characterized in that being to live as follows containing effective dose
Property composition: methanesulfonic acid FCE-26743A and tartaric acid Mo Fanselin.
2. methanesulfonic acid FCE-26743A as claimed in claim 1 and tartaric acid Mo Fanselin compositions, it is characterised in that described
Compositions in, the effective dose that each preparation unit contains methanesulfonic acid FCE-26743A is 25mg～200mg, containing tartaric acid not
The effective content of Fan Selin is 10～60mg.
3. methanesulfonic acid FCE-26743A as claimed in claim 2 and tartaric acid Mo Fanselin compositions, it is characterised in that described
Compositions in, the effective dose that each preparation unit contains methanesulfonic acid FCE-26743A is 50mg, containing tartaric acid Mo Fanselin
Effective content be 20mg.
4. methanesulfonic acid FCE-26743A as claimed in claim 3 and tartaric acid Mo Fanselin compositions, it is characterised in that combination
Thing is for treating parkinson disease and the mental sickness relevant to parkinson disease.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610712574.0A CN106309417A (en) | 2016-08-23 | 2016-08-23 | Pharmaceutical composition for treating diseases related to Parkinson's diseases |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610712574.0A CN106309417A (en) | 2016-08-23 | 2016-08-23 | Pharmaceutical composition for treating diseases related to Parkinson's diseases |
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| Publication Number | Publication Date |
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| CN106309417A true CN106309417A (en) | 2017-01-11 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201610712574.0A Pending CN106309417A (en) | 2016-08-23 | 2016-08-23 | Pharmaceutical composition for treating diseases related to Parkinson's diseases |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050119249A1 (en) * | 2003-12-02 | 2005-06-02 | Erik Buntinx | Method of treating neurodegenerative diseases using D4 and 5-HT2A antagonists, inverse agonists or partial agonists |
-
2016
- 2016-08-23 CN CN201610712574.0A patent/CN106309417A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050119249A1 (en) * | 2003-12-02 | 2005-06-02 | Erik Buntinx | Method of treating neurodegenerative diseases using D4 and 5-HT2A antagonists, inverse agonists or partial agonists |
Non-Patent Citations (3)
| Title |
|---|
| HERBERT Y MELTZER,ET AL.: "Pimavanserin, a Serotonin2A Receptor Inverse Agonist, for the Treatment of Parkinson’s Disease Psychosis", 《NEUROPSYCHOPHARMACOLOGY》 * |
| OLIVIER RASCOL,ET AL.: "New Treatments for Levodopa-Induced Motor Complications", 《MOVEMENT DISORDERS》 * |
| SAMANTHA HOLDEN,ET AL.: "Treatment of Psychosis and Dementia in Parkinson’s Disease", 《CURR TREAT OPTIONS NEUROL》 * |
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Application publication date: 20170111 |