CN109432306A - Pharmaceutical composition and its application - Google Patents

Pharmaceutical composition and its application Download PDF

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Publication number
CN109432306A
CN109432306A CN201811563718.6A CN201811563718A CN109432306A CN 109432306 A CN109432306 A CN 109432306A CN 201811563718 A CN201811563718 A CN 201811563718A CN 109432306 A CN109432306 A CN 109432306A
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parts
extract
weight
pharmaceutical composition
drug
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Inventor
刘振国
魏江磊
吴娜
宋璐
万赢
张煜
干静
袁伟恩
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XinHua Hospital Affiliated To Shanghai JiaoTong University School of Medicine
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XinHua Hospital Affiliated To Shanghai JiaoTong University School of Medicine
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/898Orchidaceae (Orchid family)
    • A61K36/8988Gastrodia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56Materials from animals other than mammals
    • A61K35/63Arthropods
    • A61K35/64Insects, e.g. bees, wasps or fleas
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/23Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/232Angelica
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/48Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/481Astragalus (milkvetch)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/65Paeoniaceae (Peony family), e.g. Chinese peony
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/71Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/74Rubiaceae (Madder family)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/80Scrophulariaceae (Figwort family)
    • A61K36/804Rehmannia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16Anti-Parkinson drugs

Abstract

The present invention provides a kind of pharmaceutical composition and its application, pharmaceutical composition includes the drug of following parts by weight: 10-20 parts of Rhizoma Gastrodiae extract, 20-40 parts of Astragalus Root P.E, 8-16 parts of prepared rehmannia root extract, 8-16 parts of radix paeoniae alba extraction, 10-20 parts of angelica extract, 8-16 parts of uncaria extract, 5-15 parts of Bombyx Batryticatus extract, and the weight of extract is pressed the weight after being dried and calculated.Pharmaceutical composition of the invention can be substantially reduced the effect of rotation AIM value compared with Western medicine.

Description

Pharmaceutical composition and its application
Technical field
The present invention relates to a kind of pharmaceutical compositions, and the invention further relates to the applications of this pharmaceutical composition, belong to Chinese medicine neck Domain.
Background technique
Parkinson's disease (Parkinson ' s disease, PD) is one kind with substantia nigra of midbrain compact part dopaminergic neuron Denaturation is the nervous system degenerative disease of major pathologic features, and disease incidence in global over-65s crowd is up to 2%.It is left-handed DOPA (L-dopa) is the precursor of dopamine (dopamine, DA), is that treatment PD is most effective, most common drug.But take L- After dopa 3-5, Most patients will appear different degrees of complication, including " on-off phenomenon ", curative effect decline and exception Involuntary movement, i.e. the unusual fluctuation disease (L-dopa induced dyskinesias, LIDs) of levodopa.LID can be serious The quality of life of PD patient is influenced, treatment means are deficient, and the treatment for being classified as middle and advanced stage PD patient by domestic and international treatment guidelines is difficult Point.Therefore, the pathogenesis for studying LID finds the hot spot that new drug target is current PD research.
Clinical research for LID, domestic and foreign scholars mostly focus on the Clinical symptoms such as its occurrence and development influence factor and Pesticide application strategy.The clinical problem that this project is also taken the lead at home using Evidence-based Medicine Approach analysis and summary motor complication: to PD The Clinical symptoms of motor complication and non-motor symptoms has carried out 6 years follow-up investigations, for the first time Primary Construction PD motor complication Assessment of risks scale carries out the analysis of PD long-term life quality of patients and Therapeutic strategy for high.The pathogenesis of LID is still not clear, The Summary of Research Advance obtained at present is as follows:
1, the fluctuation sexual stimulus of exogenous DA:
PD patient's black substance DA serotonergic neuron progressive is lost, and exogenous L-dopa half-life short used in supplementary therapy is led The DA for causing intracerebral to generate is discharged in pulse sample.In addition, serotonin (5-HT) serotonergic neuron substitutes DA serotonergic neuron, external source is carried out Conversion, storage, the release of property L-dopa.But the mode that 5-HT serotonergic neuron discharges DA is different from normal physiological status.This two Kind factor causes the fluctuation of extracellular DA to change, and leads to the fluctuation sexual stimulus to DA receptor, this is considered as the primary of LID Reason.
The ongoing method for realizing duration DA stimulation of clinical at present or research, has respective shortcoming, such as uses The problems such as medicine is inconvenient, costly and side effect.This seminar had carried out two kinds of researchs for realizing duration DA stimulation in the past: (1) 5-HT is used1AReceptor stimulating agent regulates and controls 5-HT neuronal function, improves LID after finding its medication;(2) degradable material is utilized Expect poly lactide-glycolide acid (PLGA) package L-dopa/ benserazide make nanosphere, this dosage form can slow release its The L-dopa/ benserazide of package achievees the purpose that duration DA is stimulated, and can improve and prevent LID.
2, lose DA innervation after Striatum DA receptor and non-DA receptor and signal transduction pathway variation:
Corpus straitum receives the DA energy projection neuron from midbrain, also receives from the Glutamatergic of cortex and thalamus nerve Member is incoming.Expression d1 dopamine receptor MSNs, the MSNs of expression d2 dopamine receptor are direct respectively as Basal ganglia in corpus straitum The projection neuron of projection neuron (the directpathway MSNs, dMSNs) and indirect pathway of access (indirectpathway MSNs, iMSNs) release information rolls into a ball transfer through cores such as globus pallidus, subthalamic nucleis, then is transferred to cortex Loop is formed, to play the functions such as control and the coordinated movement of various economic factors.Wherein, indirect pathway, which generates cortical motor neurons, inhibits to make With, and direct path then generates the effect of disinthibiting.
Except DA receptor, there is also non-DA receptors simultaneously on MSNs, such as N-methyl-D-aspartate type glutamate receptor (NMDA) receptor, rush ionic ɑ-methylol isoxazolepropionic acid type glutamic acid (AMPA) receptor, metabotropic glutamate receptor (Metabotropic glutamate receptor, mGluR), adenosine A2AReceptor, 1 (cannabinoid of Cannabined receptor Receptor 1, CBR1) etc..D1 receptor caused by denervation it is super quick, it is considered to be LID occur the main reason for it One, this super quick signal transduction mechanism for being attributed to abnormal activation.Intrastriatal non-DA receptor, which is recognized as, takes part in LID's Occur.
This seminar for a long time to LID occur in striatal NMDA receptors, ampa receptor, metabotropic glutamate receptor, Adenosine A2AReceptor, CBR1Expression characterization and function changes and systematic research has been done in the variation of downstream signaling pathway.Wherein We have found that the expression of glutamate receptor (NMDA, AMPA, mGluR5 receptor) and function change are especially relevant with the generation of LID.
3, the Changes of Plasticity of LID striatal neuron cynapse:
With the variation of external environment, neuron, neural circuitry function adaptive change, i.e. Changes of Plasticity can also occur. Cynapse is the sensitive part of neural plasticity variation.Synaptic plasticity includes two aspect of structure and function.Synaptic structure plasticity Quantity, volume, postsynaptic density thickness including dendritic spines etc..Dendritic spines are that the main of excitatory synapse is formed between neuron Position, metamorphosis are the important indicators of Glutamatergic neurotransmission function.The plasticity of synaptic function shows as cynapse biography Pass the enhancing or decrease of function.The long changing course of cynapse transfer function is the important behaviour form of synaptic function plasticity, packet Include long term potentiation (Long-termpotentiation, LTP), long-term depression (Long-term depression, LTD) With remove gain current potential (depotentiation).It is this plastic to sexually revise in addition, journey synaptic plasticity is also gradually realized in short-term Occur in journey in short-term (it is generally acknowledged that less than tens seconds), can restore rapidly.Journey synaptic plasticity can reinforce cynapse biography in short-term The certainty passed has an important influence on the expression of long term synaptic plasticity.Journey synaptic plasticity increases including journey in short-term in short-term (Short-term enhancement, STE), in short-term journey inhibition (Short-term depression, STD) by force.It is this two-way Synaptic plasticity can be allowed to the variation with environmental stimuli with flexible modulation synaptic function and enhance or weaken.
It is now recognized that LID is related with the synaptic plasticity variation of striatal neuron.For synaptic structure plasticity, most Closely, Suarez etc. has found that the dendritic spines density of LID mouse iMSNs has raising compared with PD group, and the dendritic spines quantity of dMSNs is restored not Obviously, but volume expands, and the cynapse transmission efficiency of dMSNs and iMSNs is prompted to have difference.For synaptic function the study found that In LID model, there are the LTP of aberrant continuation, iMSN then to show as LTD by dMSN.These results prompt LID may be with corpus straitum The change of MSNs neuron-specific sexual function is related, is related to two-way plastic sexual maladjustment, makes MSN that can not remove previous motor function and refer to Enable information.But the variation for whether being related to short term plasticity about the generation of LID at present is still not clear.
The mechanism of the Striatum LID synaptic plasticity variation is still not clear.The basic research of Striatum electrophysiological mechanism Some clues can be provided.The LTD of Striatum iMSN is formed and CBR1, D2 receptor and adenosine A2AThe signal transduction of receptor has It closes.It is related with the activation of D1/NMDA compound in the LTP recorded on MSN after high frequency stimulation Glutamatergic afferent neuron.Line Shape body goes gain current potential may be with muscarine choline receptor (M4Muscarinic Receptor), 5-HT1AReceptor, ERK access Activity it is related.
LID rat model Striatum CBR is found in this seminar early-stage study1, adenosine A2AReceptor and its downstream signal Transduction changes, and whether this is related with the LTP disappearance of LID animal model iMSN, and it is still necessary to further confirm;Nmda receptor subunit Phosphorylation increase, cell membrane distribution increases, and the combination of D1 receptor enhances, the existing relationship that continues of these and LTP also need Further research;CBR1Agonist, adenosine A2AReceptor antagonist and nmda receptor antagonist can alleviate LID symptom, need to be into one Walking clear these can be relieved regulating and controlling effect of the drug to synaptic structure, function plasticity of LID symptom.
Summary of the invention
The purpose of the present invention is to provide a kind of pharmaceutical composition and its applications, to solve the above problems.
Present invention employs following technical solutions:
A kind of pharmaceutical composition, which is characterized in that the drug including following parts by weight: 10-20 parts of Rhizoma Gastrodiae extract, Radix Astragali 20-40 parts of extract, 8-16 parts of prepared rehmannia root extract, 8-16 parts of radix paeoniae alba extraction, 10-20 parts of angelica extract, uncaria extract 8-16 parts of object, 5-15 parts of Bombyx Batryticatus extract, the weight of extract are pressed the weight after being dried and are calculated.
Preferably, pharmaceutical composition of the invention, which is characterized in that the drug including following parts by weight: Rhizoma Gastrodiae extracts 13-18 parts of object, 25-35 parts of Astragalus Root P.E, 11-14 parts of prepared rehmannia root extract, 10-14 parts of radix paeoniae alba extraction, angelica extract 11-14 parts, 11-14 parts of uncaria extract, 8-12 parts of Bombyx Batryticatus extract.
Preferably, pharmaceutical composition of the invention, which is characterized in that the drug including following parts by weight: Rhizoma Gastrodiae extracts Object 15g, Astragalus Root P.E 30g, prepared rehmannia root extract 12g, radix paeoniae alba extraction 12g, angelica extract 15g, uncaria extract 12g, Bombyx Batryticatus extract 10g.
The present invention also provides a kind of application of pharmaceutical composition in drug, which is characterized in that including following parts by weight Drug: 10-20 parts of Rhizoma Gastrodiae extract, 20-40 parts of Astragalus Root P.E, 8-16 parts of prepared rehmannia root extract, 8-16 parts of radix paeoniae alba extraction, 10-20 parts of angelica extract, 8-16 parts of uncaria extract, 5-15 parts of Bombyx Batryticatus extract, the weight of extract presses drying process Weight afterwards calculates.
Preferably, the application of pharmaceutical composition of the invention in drug, which is characterized in that including following parts by weight Drug: 13-18 parts of Rhizoma Gastrodiae extract, 25-35 parts of Astragalus Root P.E, 11-14 parts of prepared rehmannia root extract, radix paeoniae alba extraction 10-14 Part, 11-14 parts of angelica extract, 11-14 parts of uncaria extract, 8-12 parts of Bombyx Batryticatus extract.
Preferably, the application of pharmaceutical composition of the invention in drug, which is characterized in that including following parts by weight Drug: Rhizoma Gastrodiae extract 15g, Astragalus Root P.E 30g, prepared rehmannia root extract 12g, radix paeoniae alba extraction 12g, angelica extract 15g, Uncaria extract 12g, Bombyx Batryticatus extract 10g.
Further, above-mentioned application, including by the Chinese medicine composition be prepared into tablet, capsule, granule, mixture, The step of oral solution or syrup.
Further, above-mentioned application, further includes: acceptable auxiliary material in pharmacy.
Further, application of the invention also has a feature in that wherein, when being prepared into tablet, capsule, first will in The raw material of drug composition carries out decocting, after filtering out decoction, concentration, then be dried in vacuo, dry extract is obtained, is then made Grain.
Further, application of the invention, also has a feature in that wherein, and the Chinese medicine composition is carried out decocting, filter Out after decoction, concentration, then be dried in vacuo, dry extract is obtained, system needed for oral solution or syrup then is added Acceptable auxiliary material in medicine, is prepared into oral solution or syrup.
Advantageous effect of the invention
Pharmaceutical composition of the invention can be substantially reduced the effect of rotation AIM value compared with Western medicine.
Detailed description of the invention
Fig. 1 is the ImmunohistochemistryResults Results figure of the expression of each group Striatum of Rats phosphorylation DARPP-32 (THr75), In:
Figure 1A: sham-operation group;
Figure 1B: LID model group;
Fig. 1 C: Western medicine group;
Fig. 1 D: Chinese medicine small dose group;
Fig. 1 E: Chinese medicine middle dose group;
Fig. 1 F: Chinese medicine large dosage group.
Specific embodiment
Carry out the technical solution that the present invention will be described in detail below by way of specific embodiment.
The preparation process of pharmaceutical composition:
Embodiment 1
10 parts of Rhizoma Gastrodiae extract, 20 parts of Astragalus Root P.E, 8 parts of prepared rehmannia root extract, 8 parts of radix paeoniae alba extraction, Radix Angelicae Sinensis extract 10 parts of object, 8 parts of uncaria extract, 5 parts of Bombyx Batryticatus extract.
Embodiment 2
13 parts of Rhizoma Gastrodiae extract, 25 parts of Astragalus Root P.E, 11 parts of prepared rehmannia root extract, 10 parts of radix paeoniae alba extraction, Radix Angelicae Sinensis mention Take 11 parts of object, 11 parts of uncaria extract, 8 parts of Bombyx Batryticatus extract.
Embodiment 3
Rhizoma Gastrodiae extract 15g, Astragalus Root P.E 30g, prepared rehmannia root extract 12g, radix paeoniae alba extraction 12g, angelica extract 15g, uncaria extract 12g, Bombyx Batryticatus extract 10g.
Embodiment 4
18 parts of Rhizoma Gastrodiae extract, 35 parts of Astragalus Root P.E, 14 parts of prepared rehmannia root extract, 14 parts of radix paeoniae alba extraction, Radix Angelicae Sinensis mention Take 14 parts of object, 14 parts of uncaria extract, 12 parts of Bombyx Batryticatus extract.
Embodiment 5
20 parts of Rhizoma Gastrodiae extract, 40 parts of Astragalus Root P.E, 16 parts of prepared rehmannia root extract, 16 parts of radix paeoniae alba extraction, Radix Angelicae Sinensis mention Take 20 parts of object, 16 parts of uncaria extract, 15 parts of Bombyx Batryticatus extract.
Embodiment 1 can be prepared into tablet, capsule, particle to Traditional Chinese medicine composition formula provided in embodiment 5 A variety of dosage forms such as agent, mixture, oral solution or syrup.
It is acceptable auxiliary in Ying Tianjia pharmacy when tablet, capsule, granule, mixture, oral solution or syrup is made Material.
When being prepared into tablet, capsule, first the bulk pharmaceutical chemicals of Chinese medicine composition are carried out to carry out water using the water of 5 times of parts by weight It decocts, after filtering out decoction, concentration, then be dried in vacuo, particle is then made.
When preparing oral solution or syrup, Chinese medicine composition is subjected to decocting, after filtering out decoction, concentration, then carry out true Sky is dry, and acceptable auxiliary material in pharmacy needed for oral solution or syrup then is added is prepared into oral solution or syrup.
It, can also be after filtering out decoction when being prepared into oral solution or syrup, addition prepares oral solution or syrup Auxiliary material, be then concentrated, until when required viscosity, stop concentration and obtains oral solution or syrup.
The verifying of drug effect:
The preparation of 1.PD rat model
Male 2~3 monthly ages are taken, the SD rat of 180~220g of weight, behavior is laggard without spin through the confirmation of behavioral value repeatedly Row experiment.For the amobarbital (0.15ml/kg weight) of intraperitoneal injection 3% by after rat anesthesia, rat is fixed in stringent flat cranium position On stereo brain orienting instrument, after routine disinfection, scalp is cut off, removes periosteum, the rat brain stereotaxic atlas referring to written by packet new people, Determine right side medial forebrain bundle (MFB) coordinate: (1) 3.7mm after bregma, 1.7mm on the right side of sagittal suture, 7.8mm under cranial periosteum, door Tooth trace -2.4mm;(2) 4.4mm after bregma, 1.2mm on the right side of sagittal suture, 7.8mm, front tooth line -2.4mm under cranial periosteum.Cranial surgery Electric cranial drill drilling is extracted 8 μ l 6-OHDA with the micro syringe of 10 μ l, was configured with the 0.2% vitamin C same day, 4 μ of concentration G/ μ l, every injection 4 μ l, 1 μ l/min of injection speed, let the acupuncture needle remain at a certain point 10min, the slow withdraw of the needle, suture operation wound.After 3 weeks, rat abdomen Chamber injects apomorphine, starts counting after 0.5mg/kg, 10min, records 30min altogether, and 7 times/min of speed > is successful PD Model.
2. prepared by motor complication rat model
The successful part PD rat of preference pattern, give levodopa/benserazide treatment 10mg/ml levodopa and 2.5mg/ml benserazide is dissolved in containing in 0.2% ascorbic disinfection physiological saline, and the injection dosage of levodopa is 12mg/kg Add 12mg/kg benserazide, be injected intraperitoneally 2 times a day, injection time select the morning 9 when and when afternoon 5, continue 21 days.It sees Behaviouristics variation is examined, record extends with administration time, AIMs scoring situation of change.
Material and method
1. experimental animal cleaning grade healthy SD male rat 50,180~220g of weight is mentioned by Xinhua Hospital animal house For (animal certificate number: western Poole-Bi Kai experimental animal Co., Ltd SCXK (Shanghai 2008-0016)), through behavioral value repeatedly Confirm behavior without spin.
Axial AIM scoring is compared: the 8th, 15,22,29 days each comparison among groups, not statistically significant, is shown in Table 1.
2. rotation AIM scoring is compared: the 15th, mean value significant difference between 22,29 days each groups, P < 0.01.8th, 15,22,29 Its small dose group is not statistically significant compared with Western medicine group.15th, 22,29 day middle dose group is compared with small dose group, rotation AIM value is substantially reduced, and difference is statistically significant, P < 0.05.Large dosage group no difference of science of statistics compared with middle dose group, It is shown in Table 1.
1 various dose Chinese medicine group of table and Western medicine group AIM score compared with (Point)
Note: the .*P < 0.05 compared with Chinese medicine small dose group;▲ P < 0.05 compared with Western medicine group;With Chinese medicine middle dose group Compare .#P < 0.05
Pharmaceutical composition of the invention is studied to Parkinson's disease PD motor complication rat abnormal not independent behaviour and line The influence of shape body DARPP-32 (Thr75) Expression of phosphorylated inquires into chronic levodopa using rear pharmaceutical composition to unusual fluctuation disease The mechanism of action of LID.
Method
6- hydroxyl dopamine (6-OHDA) preparation PD rat model simultaneously gives levodopa treatment 4 weeks, prepares LID rat mould LID rat is randomly divided into 5 groups by type, gives rat physiological saline, i.e. LID model group, levodopa, i.e. Western medicine group respectively, with And it is small, in, large dosage of pharmaceutical composition group, set sham-operation group n=5 separately as control group, and with immunohistochemistry and Western Blotting method observes the expression of phosphorylation DARPP-32 (Thr75) in each group rat striatum body.
As a result
After levodopa is used for a long time, there are the behaviouristics such as stereotyped movement and the increased opposite side rotation of progressive and changes in PD rat Become.Pharmaceutical composition can obviously relieve the involuntary movement behavior of LID rat.Such as Fig. 1, Showed by immune group result, Western medicine group Phosphorylation DARPP-32 (THr75) expression reduces ((3.53 ± 0.20) × 10 compared with LID model group4vs.(3.85±0.30)× 104, P < 0.05), large, medium and small dosage Chinese medicine group phosphorylation DARPP-32 (THr75) expression quantity respectively (8.54 ± 0.17) × 104、(8.10±0.31)×104、(7.06±0.69)×104, (P < 0.05) is increased compared with Western medicine group.
Western blotting result and immunohistochemistry are almost the same, Western medicine group phosphorylation DARPP-32 (THr75) ash Angle value no difference of science of statistics ((0.97 ± 0.24) × 10 compared with LID model group6vs.(1.08±0.12)×106,P>0.05〕, Large, medium and small dosage Chinese medicine group rat striatum phosphorylation DARPP-32 (THr75) gray value respectively (2.40 ± 0.09) × 106、(2.37±0.16)×106、(1.44±0.14)×106, (P < 0.05) is increased compared with Western medicine group.
Conclusion
Pharmaceutical composition of the invention can reduce the Abnormal involuntary movement scoring of LID rat, and mechanism may be by The further decline for reversing phosphorylation DARPP-32 (THr75) expression, to inhibit the overactivity of PKA access;DARPP- 32 phosphorylations take part in the mechanism for the treatment of PD motor complication.

Claims (10)

1. a kind of pharmaceutical composition, which is characterized in that the drug including following parts by weight:
10-20 parts of Rhizoma Gastrodiae extract, 20-40 parts of Astragalus Root P.E, 8-16 parts of prepared rehmannia root extract, 8-16 parts of radix paeoniae alba extraction, 10-20 parts of angelica extract, 8-16 parts of uncaria extract, 5-15 parts of Bombyx Batryticatus extract, the weight of extract presses drying process Weight afterwards calculates.
2. pharmaceutical composition according to claim 1, which is characterized in that the drug including following parts by weight:
13-18 parts of Rhizoma Gastrodiae extract, 25-35 parts of Astragalus Root P.E, 11-14 parts of prepared rehmannia root extract, radix paeoniae alba extraction 10-14 Part, 11-14 parts of angelica extract, 11-14 parts of uncaria extract, 8-12 parts of Bombyx Batryticatus extract.
3. pharmaceutical composition according to claim 1, which is characterized in that the drug including following parts by weight:
Rhizoma Gastrodiae extract 15g, Astragalus Root P.E 30g, prepared rehmannia root extract 12g, radix paeoniae alba extraction 12g, angelica extract 15g, Uncaria extract 12g, Bombyx Batryticatus extract 10g.
4. a kind of application of pharmaceutical composition in drug, which is characterized in that the drug including following parts by weight:
10-20 parts of Rhizoma Gastrodiae extract, 20-40 parts of Astragalus Root P.E, 8-16 parts of prepared rehmannia root extract, 8-16 parts of radix paeoniae alba extraction, 10-20 parts of angelica extract, 8-16 parts of uncaria extract, 5-15 parts of Bombyx Batryticatus extract, the weight of extract presses drying process Weight afterwards calculates.
5. application of the pharmaceutical composition according to claim 4 in drug, which is characterized in that including following parts by weight Drug:
13-18 parts of Rhizoma Gastrodiae extract, 25-35 parts of Astragalus Root P.E, 11-14 parts of prepared rehmannia root extract, radix paeoniae alba extraction 10-14 Part, 11-14 parts of angelica extract, 11-14 parts of uncaria extract, 8-12 parts of Bombyx Batryticatus extract.
6. application of the pharmaceutical composition according to claim 4 in drug, which is characterized in that including following parts by weight Drug:
Rhizoma Gastrodiae extract 15g, Astragalus Root P.E 30g, prepared rehmannia root extract 12g, radix paeoniae alba extraction 12g, angelica extract 15g, Uncaria extract 12g, Bombyx Batryticatus extract 10g.
7. application according to any one of claims 4 to 6, which is characterized in that including preparing the Chinese medicine composition The step of at tablet, capsule, granule, mixture, oral solution or syrup.
8. the application according to any one of claim 7, which is characterized in that further include: acceptable auxiliary material in pharmacy.
9. application according to claim 7, it is characterised in that:
Wherein, when being prepared into tablet, capsule, the raw material of Chinese medicine composition is first subjected to decocting, after filtering out decoction, concentration, then It is dried in vacuo, obtains dry extract, then pelletize.
10. application according to claim 7, it is characterised in that:
Wherein, the Chinese medicine composition is subjected to decocting, after filtering out decoction, concentration, then be dried in vacuo, obtain dry mention Object is taken, acceptable auxiliary material in pharmacy needed for oral solution or syrup then is added is prepared into oral solution or syrup.
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