阅读说明：本技术 一种治疗颈椎病的纳米中药制剂及其制备方法 (Nanometer Chinese medicinal preparation for treating cervical spondylosis, and its preparation method ) 是由 刘杰 江玉娟 郝红慧 许敏 高超 潘瑞雪 王莉 张亚欣 陈克欣 于 2020-08-05 设计创作，主要内容包括：本发明提供一种治疗颈椎病的纳米中药制剂,所述纳米中药制剂的原料包括：三七1-15份,川芎3-20份,延胡索2-15份,白芍3-20份,威灵仙4-25份,葛根3-20份,羌活4-25份和一种或多种药学上可接受的辅料,通过一定的制备方法将该组方制备成纳米级别的纳米中药制剂,提高该中药组方的肠胃吸收率、药物溶解度以及生物利用度,并且将上述中药组方制备成纳米中药制剂可以使药物中的挥发油及其水溶性成分和水溶性、脂溶性都较差的成分能够很好地进行结合,提高药物稳定性的同时毒副作用小。(The invention provides a nano traditional Chinese medicine preparation for treating cervical spondylosis, which comprises the following raw materials: 1-15 parts of pseudo-ginseng, 3-20 parts of ligusticum wallichii, 2-15 parts of corydalis tuber, 3-20 parts of radix paeoniae alba, 4-25 parts of radix clematidis, 3-20 parts of radix puerariae, 4-25 parts of notopterygium root and one or more pharmaceutically acceptable auxiliary materials.)

1. A nanometer Chinese medicinal preparation for treating cervical spondylosis is characterized by comprising: 1-15 parts of pseudo-ginseng, 3-20 parts of ligusticum wallichii, 2-15 parts of corydalis tuber, 3-20 parts of radix paeoniae alba, 4-25 parts of radix clematidis, 3-20 parts of radix puerariae, 4-25 parts of notopterygium root and one or more pharmaceutically acceptable auxiliary materials;

the preparation method of the nano traditional Chinese medicine preparation for treating cervical spondylosis comprises the following steps:

(1) weighing pseudo-ginseng with the compatible amount, primarily crushing, and then preparing pseudo-ginseng fine powder into nano-powder through wet ball milling, wherein the particle size of pseudo-ginseng nano-particles is 200-400 nm;

(2) weighing the notopterygium root and the clematis root according to the compatibility, extracting the notopterygium root and the clematis root by an ultrasonic-assisted method, collecting volatile oil, concentrating the extracting solution into clear paste, mixing the volatile oil and the clear paste, and homogenizing by adopting a dynamic ultrahigh-pressure micro-jet homogenizer to obtain a nano dispersion liquid of the notopterygium root and the clematis root;

(3) weighing radix puerariae with the compatible amount, primarily crushing, and then preparing the radix puerariae fine powder into nano powder through wet ball milling, wherein the particle size of the radix puerariae nano particles is 200-400 nm;

(4) weighing radix Paeoniae alba, decocting in water twice for 2 hr and 1 hr, concentrating the filtrate, precipitating with ethanol, recovering ethanol, and concentrating to obtain fluid extract with relative density of 1.25-1.30 at 50 deg.C; homogenizing the fluid extract with dynamic ultrahigh pressure micro jet homogenizer to obtain radix Paeoniae alba nanometer dispersion;

(5) weighing rhizoma Ligustici Chuanxiong and rhizoma corydalis at a certain ratio, reflux-extracting rhizoma Ligustici Chuanxiong and rhizoma corydalis with ethanol, removing residue, recovering ethanol from the extractive solution, and concentrating to obtain fluid extract with relative density of 1.25-1.30 at 50 deg.C; homogenizing the fluid extract with dynamic ultrahigh pressure micro jet homogenizer to obtain rhizoma Ligustici Chuanxiong and rhizoma corydalis nanometer dispersion;

(6) dissolving adjuvants in water, mixing the above Notoginseng radix nanopowder, Notopterygii rhizoma, radix Clematidis nanodispersion, radix Puerariae nanodispersion, radix Paeoniae alba nanodispersion and rhizoma Ligustici Chuanxiong and rhizoma corydalis nanodispersion at a certain ratio, adding into water solution of stabilizer, and stirring to obtain nanometer Chinese medicinal preparation for treating cervical spondylosis.

2. The nano-sized traditional Chinese medicine preparation for treating cervical spondylosis as claimed in claim 1, wherein in the step (1), the notoginseng is firstly crushed into 100 meshes and sieved, and vacuum-dried at 60-70 ℃ for 60 min; taking the dried pseudo-ginseng fine powder, and carrying out wet ball milling for 15-20 h;

preferably, the particle size of the kudzu root nanoparticles is 250-350 nm.

3. The nano-sized traditional Chinese medicine preparation for treating cervical spondylosis as claimed in claim 1,

in the step (2), the technological conditions for extracting the volatile oil by the ultrasonic-assisted method are as follows: the ultrasonic power is 700-900W, preferably 800W; the ultrasonic temperature is 55-65 ℃, and preferably 60 ℃; the ultrasonic treatment time is 10-20min, preferably 15 min; the ratio of the feed to the liquid is 1:12-15(g/ml), preferably 1:12 (g/ml).

4. The nano-sized traditional Chinese medicine preparation for treating cervical spondylosis as claimed in claim 1, wherein in the step (3), kudzu root is firstly crushed into 100 meshes and sieved, and vacuum-dried at 60-70 ℃ for 60 min; taking dry radix Puerariae fine powder, and processing by wet ball milling for 18-20 h;

preferably, the particle size of the kudzu root nanoparticles is 250-350 nm.

5. The nano-sized traditional Chinese medicine preparation for treating cervical spondylosis as claimed in claim 1, wherein the stabilizer is one or more selected from sodium dodecyl sulfate, poloxamer 188, lecithin and PVP-K-30.

6. The nano traditional Chinese medicine preparation for treating cervical spondylosis as claimed in claim 1, wherein the amount of the stabilizer is 2% -4% of the mass of the traditional Chinese medicine raw materials.

7. The nano traditional Chinese medicine preparation for treating cervical spondylosis as claimed in claim 5, wherein the stabilizer is a mixture of poloxamer 188 and lecithin.

8. The nano traditional Chinese medicine preparation for treating cervical spondylosis as claimed in claim 7, wherein the mass ratio of poloxamer 188 to lecithin is 1: 2-3;

preferably, the mass ratio of poloxamer 188 to lecithin is 1: 2.

9. The nano traditional Chinese medicine preparation for treating cervical spondylosis as claimed in claim 1, wherein the parameters for homogenization treatment by using the dynamic ultrahigh pressure micro-jet homogenizer are as follows: the pre-homogenization is carried out by adopting the homogenization pressure of 500-1000bar, and then the homogenization is carried out for 15-20 times by adopting the homogenization pressure of 1500-2000 bar.

10. The use of the nano-sized traditional Chinese medicine preparation of any one of claims 1 to 9 for the treatment of cervical spondylosis.

Technical Field

The invention relates to the technical field of traditional Chinese medicine preparations for treating cervical spondylosis, in particular to a nanometer traditional Chinese medicine preparation for treating cervical spondylosis and a preparation method thereof.

Background

The information in this background section is only for enhancement of understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art that is already known to a person of ordinary skill in the art.

Cervical spondylotic radiculopathy (blood stasis, qi stagnation and venation block) belongs to the category of arthralgia in traditional Chinese medicine, cervical intervertebral disc degeneration is taken as a guide, and on the basis of intervertebral foraminal stenosis, nerve roots are subjected to mechanical compression and chemical stimulation to generate congestion, edema and inflammatory reaction to cause diseases.

Disclosure of Invention

In order to overcome the technical problems, the invention improves the preparation process of the traditional Chinese medicine formula consisting of pseudo-ginseng, ligusticum wallichii, corydalis tuber, white peony root, clematis root, kudzu root and notopterygium root, provides a nano traditional Chinese medicine preparation for treating cervical spondylosis and a preparation method thereof, improves the gastrointestinal absorption rate, the medicine solubility and the bioavailability of the traditional Chinese medicine formula, and can well combine volatile oil and water-soluble components thereof in the medicine with components with poor water solubility and fat solubility and improve the stability of the medicine and have small toxic and side effects.

Specifically, the technical scheme of the invention is as follows:

in a first aspect of the present invention, a nano-sized traditional Chinese medicine preparation for treating cervical spondylosis is provided, wherein the nano-sized traditional Chinese medicine preparation comprises the following raw materials: 1-15 parts of pseudo-ginseng, 3-20 parts of ligusticum wallichii, 2-15 parts of corydalis tuber, 3-20 parts of radix paeoniae alba, 4-25 parts of radix clematidis, 3-20 parts of radix puerariae, 4-25 parts of notopterygium root and one or more pharmaceutically acceptable auxiliary materials.

The preparation method of the nano traditional Chinese medicine preparation for treating cervical spondylosis comprises the following steps:

(1) weighing pseudo-ginseng with the compatible amount, primarily crushing, and then preparing pseudo-ginseng fine powder into nano-powder through wet ball milling, wherein the particle size of pseudo-ginseng nano-particles is 200-400 nm;

(2) weighing the notopterygium root and the clematis root according to the compatibility, extracting the notopterygium root and the clematis root by an ultrasonic-assisted method, collecting volatile oil, concentrating the extracting solution into clear paste, mixing the volatile oil and the clear paste, and homogenizing by adopting a dynamic ultrahigh-pressure micro-jet homogenizer to obtain a nano dispersion liquid of the notopterygium root and the clematis root;

the technological conditions for extracting the volatile oil by the ultrasonic-assisted method are as follows: the ultrasonic power is 700-900W, preferably 800W, the ultrasonic temperature is 55-65 ℃, preferably 60 ℃, the ultrasonic time is 10-20min, preferably 15min, and the material-liquid ratio is 1:12-15 (g/ml);

(3) weighing radix puerariae with the compatible amount, primarily crushing, and then preparing the radix puerariae fine powder into nano powder through wet ball milling, wherein the particle size of the radix puerariae nano particles is 200-400 nm;

(4) weighing radix Paeoniae alba, decocting in water twice for 2 hr and 1 hr, concentrating the filtrate, precipitating with ethanol, recovering ethanol, and concentrating to obtain fluid extract with relative density of 1.25-1.30 at 50 deg.C; homogenizing the fluid extract with dynamic ultrahigh pressure micro jet homogenizer to obtain radix Paeoniae alba nanometer dispersion;

(5) weighing rhizoma Ligustici Chuanxiong and rhizoma corydalis at a certain ratio, reflux-extracting rhizoma Ligustici Chuanxiong and rhizoma corydalis with ethanol, removing residue, recovering ethanol from the extractive solution, and concentrating to obtain fluid extract with relative density of 1.25-1.30 at 50 deg.C; homogenizing the fluid extract with dynamic ultrahigh pressure micro jet homogenizer to obtain rhizoma Ligustici Chuanxiong and rhizoma corydalis nanometer dispersion;

(6) dissolving stabilizer in water, mixing the above Notoginseng radix nanopowder, Notopterygii rhizoma, radix Clematidis nanodispersion, radix Puerariae nanodispersion, radix Paeoniae alba nanodispersion and rhizoma Ligustici Chuanxiong, and rhizoma corydalis nanodispersion at a certain ratio, adding into stabilizer water solution, and stirring to obtain nanometer Chinese medicinal preparation for treating cervical spondylosis;

the stabilizer is selected from one or more of sodium dodecyl sulfate, poloxamer 188, lecithin and PVP-K-30;

the dosage of the stabilizer is 2-4% of the mass of the traditional Chinese medicine raw materials.

In a second aspect of the invention, an application of the nano traditional Chinese medicine preparation for treating cervical spondylosis in treating cervical spondylosis is provided.

The specific embodiment of the invention has the following beneficial effects:

the prepared nano traditional Chinese medicine preparation for treating cervical spondylosis has uniform granularity, good dispersion and high stability due to the screening and adding of the stabilizer, is not easy to generate coagulation, and can promote the dissolution and the utilization of the effective components of the medicine;

according to the traditional medicament for treating cervical spondylosis, the preparation method firstly extracts effective components from raw materials in a traditional Chinese medicine formula and then prepares the medicament, but because some medicinal components have poor solubility, such as isoflavone substances in the root of kudzu vine, only part of the effective components can be extracted by the existing extraction technology, so that the waste of the effective components in a large amount of traditional Chinese medicines is caused, the root of kudzu vine is subjected to nanocrystallization, so that the effective components in the root of kudzu vine can be effectively dissolved out and utilized, the waste of medicinal materials is reduced, and the utilization rate of the medicinal materials is improved;

the nanometer preparation has small particle size, so that the medicine has great specific surface area, high effective component dissolving rate, long retention period in gastrointestinal tract and high bioavailability.

Drawings

The accompanying drawings, which are incorporated in and constitute a part of this specification, are included to provide a further understanding of the invention, and are incorporated in and constitute a part of this specification, illustrate exemplary embodiments of the invention and together with the description serve to explain the invention and not to limit the invention.

FIG. 1 is a high performance liquid chromatogram of ginsenoside Rg1 in the serum of example 1 group of mice at 8 h;

FIG. 2 is a high performance liquid chromatogram of ginsenoside Rg1 in serum of comparative example 1 group of mice for 8 h.

Detailed Description

The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out according to conventional conditions or according to conditions recommended by the manufacturers.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. The reagents or starting materials used in the present invention can be purchased from conventional sources, and unless otherwise specified, the reagents or starting materials used in the present invention can be used in a conventional manner in the art or in accordance with the product specifications. In addition, any methods and materials similar or equivalent to those described herein can be used in the methods of the present invention. The preferred embodiments and materials described herein are intended to be exemplary only.

As discussed in the background art, the agents for treating cervical spondylosis disclosed in the prior art have problems of low gastrointestinal absorption rate, poor membrane permeability, low bioavailability, and single dosage form; in addition, the ingredients in the traditional Chinese medicine are extracted except the pseudo-ginseng in the preparation method, but because the solubility of the active ingredients of part of the raw material medicines is poor, the original extraction method can only extract part of the active ingredients, so that the waste of the active ingredients in a large number of medicinal materials is caused. In view of the above, the invention improves the preparation method of the traditional Chinese medicine preparation for treating cervical spondylosis on the basis of the traditional medicament for treating cervical spondylosis, so as to obtain the nano traditional Chinese medicine preparation which has high gastrointestinal absorption rate, good membrane permeability and high bioavailability and can furthest utilize the effective components in the medicinal materials to treat cervical spondylosis.

In one embodiment of the present invention, a nano-sized traditional Chinese medicine preparation for treating cervical spondylosis is provided, wherein the nano-sized traditional Chinese medicine preparation comprises the following raw materials: 1-15 parts of pseudo-ginseng, 3-20 parts of ligusticum wallichii, 2-15 parts of corydalis tuber, 3-20 parts of radix paeoniae alba, 4-25 parts of radix clematidis, 3-20 parts of radix puerariae, 4-25 parts of notopterygium root and one or more pharmaceutically acceptable auxiliary materials;

the preparation method of the nano traditional Chinese medicine preparation for treating cervical spondylosis comprises the following steps:

(1) weighing pseudo-ginseng with the compatible amount, primarily crushing, and then preparing pseudo-ginseng fine powder into nano-powder through wet ball milling, wherein the particle size of pseudo-ginseng nano-particles is 200-400 nm;

in a specific embodiment, the Notoginseng radix is first pulverized into 100 mesh and sieved, and vacuum dried at 60-70 deg.C for 60 min; taking the dried pseudo-ginseng fine powder, and carrying out wet ball milling for 15-20 h;

in a preferred embodiment, the particle size of the pueraria nanoparticle is 250-350 nm;

the invention finds that the stability of the kudzu root nano particles is poor when the average particle size is below 200nm, aggregation is easy to occur, and the dissolution effect of active ingredients in the drug particles is reduced when the average particle size is above 400 nm.

The nano-scale dispersion liquid prepared from the panax notoginseng is more beneficial to dissolving out the effective medicinal components such as panax notoginseng saponins and the like, and is beneficial to the full absorption and utilization of the medicine in the organism.

(2) Weighing the notopterygium root and the clematis root according to the compatibility, extracting the notopterygium root and the clematis root by an ultrasonic-assisted method, collecting volatile oil, concentrating the extracting solution into clear paste, mixing the volatile oil and the clear paste, and homogenizing by adopting a dynamic ultrahigh-pressure micro-jet homogenizer to obtain a nano dispersion liquid of the notopterygium root and the clematis root;

in a specific embodiment, the process conditions for extracting the volatile oil by the ultrasonic-assisted method are as follows: the ultrasonic power is 700-900W, preferably 800W, the ultrasonic temperature is 55-65 ℃, preferably 60 ℃, the ultrasonic time is 10-20min, preferably 15min, and the material-liquid ratio is 1:12-15(g/ml), preferably 1:12 (g/ml);

the volatile oil extracted by the steam distillation method can cause part of the medicine components to generate denaturation reactions such as polymerization, oxidation and the like, thereby reducing part of the medicine effect; the method adopts an ultrasonic-assisted method to extract the volatile oil, so that the extraction rate of the volatile oil can be improved, the extraction time is shortened, the temperature rise is not obvious in the extraction process, the volatilization of effective components can be inhibited, and the original medicinal properties of the extract can be maintained; the ultrasonic extraction conditions of the invention can maximally extract the volatile oil in notopterygium root and clematis root, and the extracted volatile oil can keep good medicinal activity.

(3) Weighing radix puerariae with the compatible amount, primarily crushing, and then preparing the radix puerariae fine powder into nano powder through wet ball milling, wherein the particle size of the radix puerariae nano particles is 200-400 nm;

the puerarin which is an effective medicinal component in the kudzuvine root is an isoflavone substance, the solubility of the puerarin in water and ethanol is not high, the extraction rate of the puerarin which can be obtained by the existing puerarin extraction method is not high, and the method of extracting the effective component from the kudzuvine root and then combining the effective component into the medicine wastes most of the effective component in the kudzuvine root, so that the effective component can not be fully utilized; therefore, in order to improve the full utilization of the puerarin and increase the dissolution of the puerarin in the medicine, the kudzuvine root is prepared into nano dispersion liquid, so that the puerarin in the kudzuvine root is fully utilized.

In a preferred embodiment, the particle size of the pueraria nanoparticle is 250-350 nm;

the invention finds that the stability of the kudzu root nano particles is poor when the average particle size is below 200nm, aggregation is easy to occur, and the dissolution effect of active ingredients in the drug particles is reduced when the average particle size is above 400 nm.

In a specific embodiment, radix Puerariae is first pulverized into 100 mesh and sieved, and vacuum dried at 60-70 deg.C for 60 min; taking the dried fine powder of the kudzuvine root, and carrying out wet ball milling processing for 18-20 h.

(4) Weighing radix Paeoniae alba, decocting in water twice for 2 hr and 1 hr, concentrating the filtrate, precipitating with ethanol, recovering ethanol, and concentrating to obtain fluid extract with relative density of 1.25-1.30 at 50 deg.C; homogenizing the fluid extract with dynamic ultrahigh pressure micro jet homogenizer to obtain radix Paeoniae alba nanometer dispersion;

(5) weighing rhizoma Ligustici Chuanxiong and rhizoma corydalis at a certain ratio, reflux-extracting rhizoma Ligustici Chuanxiong and rhizoma corydalis with ethanol, removing residue, recovering ethanol from the extractive solution, and concentrating to obtain fluid extract with relative density of 1.25-1.30 at 50 deg.C; homogenizing the fluid extract with dynamic ultrahigh pressure micro jet homogenizer to obtain rhizoma Ligustici Chuanxiong and rhizoma corydalis nanometer dispersion;

(6) dissolving stabilizer in water, mixing the above Notoginseng radix nanopowder, Notopterygii rhizoma, radix Clematidis nanodispersion, radix Puerariae nanodispersion, radix Paeoniae alba nanodispersion and rhizoma Ligustici Chuanxiong, and rhizoma corydalis nanodispersion at a certain ratio, adding into stabilizer water solution, and stirring to obtain nanometer Chinese medicinal preparation for treating cervical spondylosis;

the stabilizer is selected from one or more of sodium dodecyl sulfate, poloxamer 188, lecithin and PVP-K-30;

the dosage of the stabilizer is 2-4% of the mass of the traditional Chinese medicine raw materials.

In a specific embodiment, the stabilizer is a mixture of poloxamer 188 and lecithin;

preferably, the mass ratio of the poloxamer 188 to the lecithin is 1: 2-3;

further preferably, the mass ratio of poloxamer 188 to lecithin is 1: 2;

the active action of Chinese medicine in treating diseases depends on its chemical components, such as saponin, flavone and alkaloid, etc. and is closely related to the physical state of medicine, such as granularity and surface area of Chinese medicine material, especially when the granularity of Chinese medicine reaches a certain range, even the quality of Chinese medicine is changed. The nanometer level Chinese medicine grains obtained by dynamic ultrahigh pressure micro jet homogenizing process have small size and great surface energy, so that the nanometer level Chinese medicine grains are unstable and easy to re-aggregate into great grains to affect the medicine effect of nanometer level Chinese medicine preparation. The problem of instability of the nano preparation can be solved by adding the stabilizer, and the stabilizer is screened aiming at the traditional Chinese medicine components of pseudo-ginseng, ligusticum wallichii, corydalis tuber, white paeony root, clematis chinensis, kudzu-vine root and notopterygium root. According to the invention, sodium dodecyl sulfate, poloxamer 188, lecithin and PVP-K-30 in the stabilizer have a good stabilizing effect on the nano preparation of the formula, but the influences of the stabilizer on the dissolution rate of active ingredients in the medicine and the solubility and bioavailability need to be considered, so that the pseudo-ginseng, ligusticum wallichii, corydalis tuber, white paeony root, clematis root, kudzu vine root and notopterygium root nano preparation prepared by combining poloxamer 188 and lecithin has good stability, high dissolution rate and good bioavailability.

In a specific embodiment, the parameters of the homogenization treatment by the dynamic ultrahigh-pressure micro-jet homogenizer are set as follows: the pre-homogenization is carried out by adopting the homogenization pressure of 500-1000bar, and then the homogenization is carried out for 15-20 times by adopting the homogenization pressure of 1500-2000 bar.

In one embodiment of the invention, the application of the nanometer Chinese medicinal preparation for treating cervical spondylosis in treating cervical spondylosis is provided.