阅读说明：本技术 一种用于迟滞早期帕金森发展进程的药物组合物 (Pharmaceutical composition for delaying early Parkinson development process ) 是由 沈洁 沈艳 于 2020-07-02 设计创作，主要内容包括：本发明提供一种包含NMN的药物组合物及其制备方法,用于迟滞早期帕金森病的发展进程。NMN对迟滞PD模型小鼠早期帕金森发展进程有一定的作用效力,且呈现剂量依赖性,不如药物组合物的迟滞效果,在相同用药时长时,组合物对迟滞PD模型小鼠早期帕金森发展效果显著优于NMN。组合物对迟滞PD模型小鼠早期帕金森发展进程呈时间依赖性,用药时间越长,迟滞效果越好,但是治疗效果不及预防效果。(The invention provides a pharmaceutical composition containing NMN and a preparation method thereof, which are used for delaying the development process of early-stage Parkinson's disease. The NMN has certain effect efficacy on the delayed PD model mouse early-stage Parkinson development process, presents dose dependence, is not as good as the delayed effect of a pharmaceutical composition, and has a remarkably better effect on the delayed PD model mouse early-stage Parkinson development than the NMN when the dosage is the same. The composition is time-dependent on the early Parkinson development process of the delayed PD model mouse, the longer the administration time is, the better the delayed effect is, but the treatment effect is not as good as the prevention effect.)

1. A pharmaceutical composition comprising NMN and an extract of Leontopodium alpinum, wherein said extract of Leontopodium alpinum is prepared by the steps of:

1) adding an organic reagent into the extraction raw material and uniformly mixing;

2) carrying out ultrasonic wall breaking treatment on the mixed product;

3) carrying out high-temperature water leaching on the wall-broken treatment product;

4) carrying out solid-liquid separation on the leaching product and reserving liquid;

5) concentrating the separated liquid, and freeze-drying to obtain the extract of the Hibiscus alpinus Leontopodium.

2. The composition of claim 1, wherein: NMN: the mass part ratio of the alpine edelweiss extract is 1-10: 40-100.

3. The composition of claim 1, wherein: NMN: the mass part ratio of the alpine edelweiss extract is 2-5: 50-80.

4. The composition of claim 1, wherein: NMN: the mass part ratio of the alpine edelweiss extract is 1: 20.

5. the composition of claim 1, wherein: the raw material for extracting the edelweiss extract is fresh edelweiss or plant cell culture.

6. The composition according to claim 1 or 6, characterized in that: the raw material for extracting the alpine edelweiss extract is plant cell culture.

7. A preparation process of a pharmaceutical composition comprises the following steps:

1) adding 2 times of lower alcohol (the material-liquid ratio is 1:2(m/v)) into 1 part of fresh alpine edelweiss grass powder or fresh alpine edelweiss cell culture by mass, and uniformly mixing;

2) the mixed product is subjected to 200-300W ultrasonic wall breaking treatment at the temperature of 25-30 ℃ for 10-30 min;

3) adding 5-10 times volume of pure water into the product of the ultrasonic wall breaking treatment, and leaching for 1-2h at 80-120 ℃;

4) centrifuging the leaching product by 4000-10000g for solid-liquid separation and reserving liquid;

5) concentrating the separated liquid, and freeze-drying to obtain Hibiscus alpinus extract;

6) weighing NMN with formula amount, and mixing with the extract of the leontopodium alpinum at equal ratio to obtain the pharmaceutical composition;

7) adding a proper amount of pharmaceutically acceptable auxiliary materials into the pharmaceutical composition, and forming the preparation to obtain the NMN medicament for treating AD.

8. The process according to claim 7, characterized in that: the lower alcohol is ethanol or butanediol.

9. The production process according to claim 7 or 8, characterized in that: the lower alcohol is ethanol.

10. A pharmaceutical composition comprises NMN, an extract of Leontopodium alpinum and pharmaceutically acceptable excipients, and is characterized in that the pharmaceutical composition is used for delaying the development process of early Parkinson's disease.

Technical Field

The invention belongs to the technical field of medicines, and particularly provides a pharmaceutical composition for delaying early Parkinson development.

Background

Parkinson's Disease (PD) is a common chronic progressive nervous system degeneration lifelong disease in the elderly, and the disease cases are characterized in that the DA (nerve neuron) of the nigra-striatum pathway changes and is deficient, so that the content of the midbrain nigra dopamine transmitter is obviously reduced. Oxidative stress injury is considered as one of the important causes of parkinson's disease, and the pathogenesis is: a free radical scavenging system exists in a normal organism, superoxide dismutase, glutathione peroxidase, reduced glutathione and the like are mainly contained in the brain, redundant free radicals can be timely scavenged, and cells in the brain are prevented from being damaged by the free radicals. Under normal conditions, the production and elimination of free radicals are in equilibrium, and once the equilibrium is broken, the production of free radicals increases or the elimination capacity decreases, with the result that the toxic effects of free radicals dominate, causing cell and body damage, and thus inducing parkinson.

Research shows that NMN can improve the survival rate of nerve cells, reduce apoptosis, recover NPD + and ATP levels, inhibit apoptosis, resist oxidative stress damage of organisms and improve energy metabolism disorder induced by mitochondrial inhibitors, and is a potential clinical medicine for treating Parkinson. However, the high manufacturing cost and the ultra-high drug concentration limit the clinical popularization and application of the NMN for treating PD, so that the reduction of the manufacturing cost or the reduction of the drug concentration becomes the key for applying the NMN to the PD treatment.

Disclosure of Invention

The invention provides a pharmaceutical composition containing NMN, which is used for delaying the development process of early-stage Parkinson's disease. The invention also provides a preparation method of the NMN pharmaceutical composition for delaying the development process of early Parkinson's disease.

The pharmaceutical composition provided by the invention comprises NMN and an extract of edelweiss. The pharmaceutical composition is a composition with medical activity for preparing a medicament, and comprises a proper amount of pharmaceutically acceptable auxiliary materials besides the medical active composition.

Further, in the pharmaceutical composition of the present invention, the ratio of NMN: the mass ratio of the alpine edelweiss extract is 1-10: 40-100, preferably 2-5:50-80, more preferably 1: 20.

when fresh grass of alpine edelweiss or plant cell culture is used as an extraction raw material, the extraction method preferably comprises the following steps:

1) adding an organic reagent into the extraction raw material and uniformly mixing;

2) carrying out ultrasonic wall breaking treatment on the mixed product;

3) carrying out high-temperature water leaching on the wall-broken treatment product;

4) carrying out solid-liquid separation on the leaching product and reserving liquid;

5) concentrating the separated liquid, and freeze-drying to obtain the extract of the Hibiscus alpinus Leontopodium.

Preferably, the raw material for extracting the edelweiss is a plant cell culture of the edelweiss.

Furthermore, the NMN with the formula amount is weighed and evenly mixed with the extract of the leontopodium alpinum to obtain the pharmaceutical composition.

Furthermore, a proper amount of pharmaceutically acceptable auxiliary materials are added into the medicine composition, and the preparation is formed to obtain the medicine for delaying the development process of early Parkinson.

In the preparation process of the pharmaceutical composition, the preparation method comprising the following processes is preferred:

1) adding 2 times of lower alcohol (the material-liquid ratio is 1:2(m/v)) into 1 part of fresh alpine edelweiss grass powder or fresh alpine edelweiss cell culture by mass, and uniformly mixing;

2) the mixed product is subjected to 200-300W ultrasonic wall breaking treatment at the temperature of 25-30 ℃ for 10-30 min;

3) adding 5-10 times volume of pure water into the product of the ultrasonic wall breaking treatment, and leaching for 1-2h at 80-120 ℃;

4) centrifuging the leaching product by 4000-10000g for solid-liquid separation and reserving liquid;

5) concentrating the separated liquid, and freeze-drying to obtain Hibiscus alpinus extract;

6) weighing NMN with formula amount, and mixing with the extract of the leontopodium alpinum at equal ratio to obtain the pharmaceutical composition;

7) adding a proper amount of pharmaceutically acceptable auxiliary materials into the medicinal composition, and forming a preparation to obtain the medicament for delaying the early development process of the Parkinson's disease.

Preferably, the lower alcohol in the process for the preparation of the pharmaceutical composition is ethanol or butanediol, more preferably ethanol.

Preferably, the concentration in the process for preparing the pharmaceutical composition means concentration under reduced pressure.

In the present invention, the term "pharmaceutically acceptable excipient" includes pharmaceutically acceptable carriers, excipients, diluents and the like, which are compatible with the pharmaceutically active ingredient. The use of pharmaceutically acceptable excipients for the preparation of pharmaceutical preparations is well known to those skilled in the art.

The pharmaceutical composition of the present invention comprises the NMN and leontopodium alpinum extract composition of the present invention as an active ingredient, and the composition is combined with pharmaceutically acceptable adjuvants (such as carriers, excipients, diluents, etc. well known to those of ordinary skill in the art) to be formulated into various formulations, preferably solid formulations and liquid formulations, such as tablets, pills, capsules, powders, suspensions, granules, syrups, emulsions, suspensions, etc., and various sustained release formulations, preferably in oral administration form.

The medicine composition is used for delaying the development process of early Parkinson's disease.

The inventor finds that the content of caffeoylquinic acid substances in the alpine edelweiss extract can obviously influence the effect of the pharmaceutical composition, the caffeoylquinic acid substances are easy to lose in the processing (freeze thawing or drying) process of the alpine edelweiss, and the efficacy of the pharmaceutical composition can be ensured only when fresh alpine edelweiss or cell cultures are used as extraction raw materials. The caffeoylquinic acid substances are probably main components for improving the transfer of choline in the brain, and can be used together with NMN to remarkably reduce the drug concentration of NMN in the process of delaying early Parkinson development and improve the action efficacy of NMN.

Detailed Description

Hereinafter, specific embodiments of the present invention will be described in detail. Well-known structures or functions may not be described in detail in the following embodiments in order to avoid unnecessarily obscuring the details. Unless defined otherwise, technical and scientific terms used in the following examples have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.