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CN119523988A - A pharmaceutical composition for treating nervous system diseases - Google Patents

A pharmaceutical composition for treating nervous system diseases Download PDF

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Publication number
CN119523988A
CN119523988A CN202411888770.4A CN202411888770A CN119523988A CN 119523988 A CN119523988 A CN 119523988A CN 202411888770 A CN202411888770 A CN 202411888770A CN 119523988 A CN119523988 A CN 119523988A
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China
Prior art keywords
borneol
pharmaceutical composition
eslicarbazepine acetate
group
nervous system
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Pending
Application number
CN202411888770.4A
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Chinese (zh)
Inventor
王进
霍颖浩
王永静
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Second Hospital of Hebei Medical University
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Second Hospital of Hebei Medical University
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Priority to CN202411888770.4A priority Critical patent/CN119523988A/en
Publication of CN119523988A publication Critical patent/CN119523988A/en
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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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs

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  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Psychology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

本发明提供了一种治疗神经系统疾病的药物组合物，活性成分由醋酸艾司利卡西平和天然冰片组成，醋酸艾司利卡西平和天然冰片的重量比为4.5～7.5：1；所述药物组合物可以用于制备治疗神经系统疾病的药物，尤其是帕金森病，改善运动障碍。The invention provides a pharmaceutical composition for treating nervous system diseases, wherein the active ingredients are composed of eslicarbazepine acetate and natural borneol, and the weight ratio of eslicarbazepine acetate to natural borneol is 4.5-7.5:1; the pharmaceutical composition can be used to prepare drugs for treating nervous system diseases, especially Parkinson's disease, and improving movement disorders.

Description

Pharmaceutical composition for treating nervous system diseases
Technical Field
The invention belongs to the technical field of medicines, and in particular relates to a pharmaceutical composition for treating nervous system diseases.
Background
The nervous system diseases are a group of nervous system degenerative diseases with undefined etiology and unclear pathological mechanism, but are mostly caused by abnormal aggregation of proteins in nerve cells, so that neurons are denatured and apoptotic. At present, no mature and effective method exists in the aspect of treating nervous system diseases.
Parkinson's Disease (PD) is a serious degenerative nervous system disease, and researches on the PD of people with the disease mainly comprise middle-aged and elderly people show that the PD incidence rate of people over 60 years old in China is about 1% -2%, and the PD incidence rate of people with the disease accounts for about 300 ten thousand Parkinson patients, and accounts for 50% of the people with the disease worldwide, so that the PD has become a large national parkinsonism.
At present, no clear etiology of Parkinson's disease is known, and it is presumed that the cause may be related to genetic factors, living environment, age of patients and the like. The disease has the characteristics of long disease course, incapability of self-healing, multiple complications and the like, the early stage of the patient mainly shows stationary tremors, gait abnormality, slow action and other symptoms can also appear along with the aggravation of the disease course, and simultaneously, the patient seriously reduces the life quality of the patient along with non-movement symptoms such as cognitive dysfunction, sleep disorder, anxiety, depression, constipation, dysphagia and the like.
The drug for treating epilepsy developed by the pharmaceutical company of the eslicarbazepine acetate family of portugal Bial was approved and marketed in europe in 2009, and the structure is shown below. It is a novel sodium ion channel blocker, specifically acting on ion channels, preventing it from returning to active state, thereby further reducing its repeated activation efficiency.
Borneol is a common traditional Chinese medicine, is an extraction processing product of fresh branches and leaves of camphor of Lauraceae, mainly comprises D-borneol (borneo um), the content of the D-borneol is not less than 96%, blumea balsamifera tablet is crystal of fresh leaves of blumea balsamifera of Compositae, mainly comprises L-borneol, the content of the L-borneol is not less than 85% calculated by borneol, and synthetic borneol is a refined product (also called as machine-made borneol) synthesized by a chemical method by taking turpentine as a raw material, is a racemate and contains a certain of isoborneol (isoborneo 1), and the content of the borneol is not less than 55%.
In addition, D-borneol is also called (+) -2-camphol and D-camphol, and L-borneol is also called (-) -2-camphol and is also called blumea balsamifera.
Natural borneol has the best effect, but because of resource limitation, synthetic borneol is mostly used for replacing natural borneol in the traditional Chinese patent medicines. In addition, the content of the dextroborneol in the natural borneol is 96 percent, and a certain amount of impurities still exist, so that the medication safety is possibly influenced, and therefore, people purify the natural borneol, and the (+) -2-camphol with the purity of more than or equal to 98 percent is commercially available at present.
There is no report in the prior art that eslicarbazepine acetate is used in combination with borneol for treating neurological diseases, especially parkinsonism.
Disclosure of Invention
The inventor unexpectedly discovers in the research that the pharmaceutical composition of eslicarbazepine acetate and borneol, which have synergistic effect, can obviously improve the nervous system diseases, especially the dyskinesia of the parkinsonism, and provides a new thought for safely, effectively and economically treating the parkinsonism clinically.
The invention aims to provide a pharmaceutical composition for treating nervous system diseases, the active ingredients of the pharmaceutical composition are eslicarbazepine acetate and borneol, and the pharmaceutical composition has a synergistic effect and can obviously improve the symptoms of parkinsonism.
In order to achieve the above purpose, the invention adopts the following technical scheme:
A pharmaceutical composition for treating nervous system diseases comprises licarbazepine acetate and Borneolum Syntheticum as active ingredients.
In the pharmaceutical composition, the borneol is preferably natural borneol, and more preferably natural borneol with the content of the right camphol not lower than 98 percent.
In the pharmaceutical composition, the weight ratio of eslicarbazepine acetate to borneol is 20:1-1:20, the preferable weight ratio is 1-20:1, the more preferable weight ratio is 2-20:1, the more preferable weight ratio is 3-10:1, and the most preferable weight ratio is 4.5-7.5:1.
Further, in the composition, the weight ratio of eslicarbazepine acetate to natural borneol is 4.5-7.5:1, and more preferably 6:1.
The pharmaceutical composition can also contain pharmaceutically acceptable auxiliary materials to prepare oral preparations or injections, wherein the oral preparations comprise, but are not limited to, capsules, tablets, granules and oral liquid, the injections comprise, but are not limited to, sterile powder for injection, water injection, sodium chloride or glucose intravenous transfusion, and the oral preparations are further preferably prepared.
In the above pharmaceutical composition, the pharmaceutically acceptable auxiliary materials include additives, wherein the additives are at least one selected from a filler, a diluent, a disintegrating agent, an adhesive, a lubricant, a glidant, a surfactant, a solvent, a flavoring agent and a preservative.
The filler or diluent comprises saccharides such as lactose, sucrose, glucose, mannitol, sorbitol, and dextrin, starches such as starch, pregelatinized starch, alpha-starch, and dextrin, celluloses such as microcrystalline cellulose, gum arabic, and dextran, and inorganic salts such as calcium sulfate, calcium hydrogen phosphate, medicinal calcium carbonate, light anhydrous silicic acid, synthetic aluminum silicate, calcium silicate, and magnesium aluminosilicate.
The lubricant or glidant or antisticking agent comprises stearic acid, metal stearate such as calcium stearate or magnesium stearate, talcum powder, colloidal silicon dioxide, micro-powder silica gel, hydrogenated vegetable oil, polyethylene glycol, lauryl sulfate such as sodium lauryl sulfate or magnesium lauryl sulfate, silicate such as silicic anhydride or silicate hydrate, etc.
The binder comprises distilled water, ethanol with different concentrations, starch slurry, hydroxypropyl methylcellulose, hydroxypropyl cellulose, povidone, ethylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, polyethylene glycol and compounds similar to the excipients.
The disintegrating agent comprises cellulose derivatives such as low-substituted hydroxypropyl cellulose, carboxymethyl cellulose calcium or cross-linked sodium carboxymethyl cellulose, cross-linked polyvinylpyrrolidone, and chemically modified starch/cellulose such as carboxymethyl starch or sodium carboxymethyl starch.
The surfactant comprises tween-80, sodium dodecyl sulfate, sodium stearate sulfonate and the like.
The antioxidant comprises sodium bisulphite, sodium metabisulfite, sodium sulfite, dried sodium sulfite, sodium thiosulfate, ascorbic acid, methionine (methionine), thiourea, phosphoric acid, citric acid and the like.
The antiseptic or antibacterial agent comprises benzoic acid, sodium benzoate, sorbic acid, ethanol, parahydroxybenzoates (parabens), benzalkonium bromide, o-phenylphenol, benzyl alcohol, phenethyl alcohol, sodium propionate, sorbic acid, eucalyptus oil, cassia oil, peppermint oil and the like.
The flavoring agent comprises sweetener such as saccharin sodium, aspartame, syrup, stevioside, mannitol, sorbitol, mannose, galactose, maltose, fructose, glucose, sucrose, etc., sour flavoring agent such as citric acid, malic acid or tartaric acid, and aromatic agent such as oleum Foeniculi, oleum Menthae Dementholatum, menthol, peppermint water, oleum Cinnamomi, lemon essence, lemon oil, and flavoring agent with various flavors.
The pharmaceutical composition of the present invention may be formulated into various dosage forms suitable for clinical administration as described above using appropriate excipients according to any method conventionally used well known in the pharmaceutical arts.
The invention also aims to provide the application of the pharmaceutical composition, namely the application of the pharmaceutical composition in preparing medicines for treating nervous system diseases, preferably Parkinson's disease, and the pharmaceutical composition can significantly improve dyskinesia caused by nervous system diseases.
Compared with the prior art, the invention has the following advantages:
according to the invention, the eslicarbazepine acetate and the natural borneol in a specific dosage proportion are combined for the first time, so that the illness state of a Parkinson model mouse can be effectively improved, the effect is obviously better than that of the eslicarbazepine acetate or the natural borneol in the same dosage, and the eslicarbazepine acetate and the natural borneol have obvious synergistic effect.
The pharmaceutical composition can be developed into a pharmaceutical composition for treating nervous system diseases, and is expected to have good social and economic benefits.
Detailed Description
The invention discloses a pharmaceutical composition for treating nervous system diseases and a preparation method thereof, and a person skilled in the art can refer to the content of the invention and combine related principles of pharmacy and pharmacology to properly improve technological parameters. It is expressly noted that all such similar substitutions and modifications will be apparent to those skilled in the art, and are deemed to be included within the scope of the present invention. While the invention has been described with reference to preferred embodiments, it will be apparent to those skilled in the relevant art that variations and modifications can be made in the methods and applications described herein, or in appropriate changes and combinations, without departing from the spirit and scope of the invention.
For a better understanding of the present application, and not to limit its scope, all numbers expressing quantities, percentages, and other values used in the present application are to be understood as being modified in all instances by the term "about". Each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.
The content of natural borneol, namely, right borneol (right borneol) is 98.5 percent.
The content of L-borneol in the ai pian is 88.7 percent.
The content of synthetic borneol, borneol is 63.1 percent.
Test example 1 parkinsonism mouse neural function test
1 Animal experiment Material
1.1 Medicine:
The test medicine comprises eslicarbazepine acetate, natural borneol, synthetic borneol (synthetic borneol), eslicarbazepine acetate and natural borneol composition, eslicarbazepine acetate and synthetic borneol composition.
1.2 Test animals and groups
C57BL/6 mice, male, 6-8 weeks old, were acclimatized for one week in a standard feeding environment (free diet and drinking water, alternating day and night, 12 hours each).
Training the rotating rod 5 days before molding, training the rotating rod 2 times a day, and training the rotating rod 1 day before molding, wherein the rotating rod can be put into groups after being qualified.
The experimental animals were divided into a normal control group, a model control group, a positive drug group (levodopa), a drug administration group 11 of the present invention (eslicarbazepine acetate group, natural borneol group, synthetic borneol group, tablet group, eslicarbazepine acetate+natural borneol 1 group (weight ratio of 3:1), eslicarbazepine acetate+natural borneol 2 group (weight ratio of 4.5:1), eslicarbazepine acetate+natural borneol 3 group (weight ratio of 6:1), eslicarbazepine acetate+synthetic borneol group (weight ratio of 6:1), eslicarbazepine acetate+tablet group (weight ratio of 6:1), eslicarbazepine acetate+natural borneol 4 group (weight ratio of 7.5:1), eslicarbazepine acetate+natural borneol 5 group (weight ratio of 10:1)), and 8 animals each.
Molding, namely injecting 30mg/kg physiological saline into the abdominal cavity of a normal control group, and continuously injecting for 7d, wherein the physiological saline is injected 1 time a day. The model control group, the positive drug group and the administration group 11 of the invention were subjected to intraperitoneal injection of MPTP at a dose of 30mg/kg, 1 time a day, and 7 days continuously.
After the molding, the administration of the gastric lavage was started from day 8. Each group of mice was weighed before daily lavage experiments and the dose was calculated from body weight. The administration group 11 of the present invention was subjected to intragastric administration of 10 mg/kg-1 of the levodopa suspension according to the administration of 10 mg/kg-1 of the drug or the pharmaceutical composition and the positive administration group. The normal control group and the model control group were given purified water corresponding to 10ml kg-1 for gastric lavage. 1 time a day for 28 consecutive days.
Stick rotation behavior test after 1h of gastric lavage on day 28.
The mice were placed on a rotating rod of 3cm diameter and the rotational speed was adjusted to 30r/min, 8 mice were measured simultaneously at a time, 1 in each compartment. The time elapsed from the start of rotation of the rotor to the drop of the rotor was recorded within 5 minutes. The scoring standard is 0-10s-0 min, 10-30s-1 min, 30-50s-2 min, 50-70s-3 min, 70-90s-4 min, 90-120s-5 min, and more than 120s-6 min
2. Test results
Note that ※※ P <0.01, compared to the normal control group (C57 BL/6)
Note that P <0.05, P <0.01, compared to model control group
Note #P<0.05,## P <0.01, compared to eslicarbazepine acetate group
As can be seen from table 1:
(1) Compared with the normal control group (C57 BL/6), the model control group has significantly reduced rod turning time, significantly reduced rod turning score (p < 0.01), and very significant difference, which indicates that the Parkinson model is successful.
(2) The eslicarbazepine acetate group showed an increase in the time to rod compared to the model control group, an increase in rod score, but no significant difference (P > 0.05), indicating only a weak improvement in parkinsonism mice when used alone.
(3) Compared with the model control group, the time for turning the sticks of the natural borneol group, the synthetic borneol group and the moxa slice group is slightly increased, the scores of the turning the sticks are slightly increased, and the sticks have no obvious difference (P is more than 0.05), which indicates that when the natural borneol, the synthetic borneol and the moxa slice are independently used, the improvement effect on parkinsonism mice is basically not generated.
(4) Compared with a model control group, eslicarbazepine acetate, a natural borneol composition group and eslicarbazepine acetate and natural borneol composition group with the weight ratio of 3:1 are compared, the rod turning time is obviously prolonged, the rod turning score is obviously increased, obvious difference (P < 0.05) is provided, the effect of obviously improving parkinsonism mice is shown, parkinsonism can be treated, but compared with eslicarbazepine acetate, the effect of obviously improving parkinsonism is not provided (P > 0.05).
(5) Compared with a model control group, eslicarbazepine acetate, a natural borneol composition group and eslicarbazepine acetate, a natural borneol composition group, a weight ratio of 7.5:1, wherein the weight ratio of eslicarbazepine acetate to natural borneol composition group is 4.5:1, the rotating rod time is obviously prolonged, the rotating rod score is obviously increased, the significant difference (P < 0.01) is shown, the significant improvement effect on parkinsonism mice is shown, parkinsonism can be treated, and compared with eslicarbazepine acetate, the significant difference (P < 0.05) is obviously better than that of eslicarbazepine acetate. The eslicarbazepine acetate and natural borneol composition with the weight ratio of 4.5-7.5:1 are indicated to have a synergistic effect and a remarkably enhanced treatment effect, and particularly the eslicarbazepine acetate and natural borneol composition with the weight ratio of 6:1 have better treatment effect.
(6) Eslicarbazepine acetate, synthetic borneol composition group with the weight ratio of 6:1, eslicarbazepine acetate and tablet composition group with the weight ratio of 6:1, the rod turning time is prolonged, the rod turning score is increased, but the remarkable difference (P > 0.05) is not caused, the treatment effect is remarkably inferior to that of eslicarbazepine acetate and natural borneol composition group with the weight ratio of 6:1, and the treatment effect is only slightly improved on parkinsonism mice.
The experiment shows that the composition of eslicarbazepine acetate and natural borneol can greatly improve dyskinesia of parkinsonism mice, and the effect is obviously higher than that of single administration of eslicarbazepine acetate or natural borneol and slightly better than that of control levodopa. The experimental result shows that the composition of eslicarbazepine acetate and natural borneol can be used for preparing medicaments for treating and preventing the parkinsonism.
The experiment shows that the composition of eslicarbazepine acetate and natural borneol has obvious synergistic effect. The pharmaceutical composition has the prospect of being developed into a medicament for treating nervous system diseases, in particular to a medicament for treating parkinsonism, and has good prospect.

Claims (10)

1. A pharmaceutical composition for treating nervous system diseases is characterized in that the active ingredients consist of licarbazepine acetate and borneol.
2. The pharmaceutical composition of claim 1, wherein the borneol is natural borneol.
3. The pharmaceutical composition according to claim 2, wherein the content of right borneol in the natural borneol is not less than 98%.
4. The pharmaceutical composition of claim 3, wherein the weight ratio of licarbazepine acetate to natural borneol is 4.5-7.5:1.
5. A pharmaceutical composition according to claim 3, wherein the weight ratio of licarbazepine acetate to natural borneol is 6:1.
6. The pharmaceutical composition of claim 1, further comprising a pharmaceutically acceptable adjuvant.
7. The pharmaceutical composition of claim 6, which can be an oral preparation or an injection.
8. The pharmaceutical composition according to any one of claims 1 to 7, wherein the neurological disorder is parkinson's disease.
9. Use of a pharmaceutical composition according to any one of claims 1 to 7 for the preparation of a medicament for the treatment of neurological disorders.
10. The use according to claim 8, wherein the neurological disorder is parkinson's disease.
CN202411888770.4A 2024-12-20 2024-12-20 A pharmaceutical composition for treating nervous system diseases Pending CN119523988A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202411888770.4A CN119523988A (en) 2024-12-20 2024-12-20 A pharmaceutical composition for treating nervous system diseases

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202411888770.4A CN119523988A (en) 2024-12-20 2024-12-20 A pharmaceutical composition for treating nervous system diseases

Publications (1)

Publication Number Publication Date
CN119523988A true CN119523988A (en) 2025-02-28

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
CN202411888770.4A Pending CN119523988A (en) 2024-12-20 2024-12-20 A pharmaceutical composition for treating nervous system diseases

Country Status (1)

Country Link
CN (1) CN119523988A (en)

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