阅读说明：本技术 一种药物组合、其制备方法及在制备抗颈椎病药物中的应用 (Medicine composition, preparation method thereof and application thereof in preparation of anti-cervical-vertebra medicine ) 是由 江玉娟 刘杰 高超 王莉 崔阳 胡文芳 王振 郝洪慧 于 2021-01-29 设计创作，主要内容包括：本发明具体涉及一种药物组合、其制备方法及在制备抗颈椎病药物中的应用。为了解决现有药物作用效果单一的问题,本发明目的在于提供了一种内外兼治的治疗方法,通过内外和外用同时进行,实现缩短神经根颈椎病的治疗周期,降低复发概率。为了实现该技术目的,本发明针对现有的颈痛颗粒剂及东方活血膏进行了优化,通过合理调整药味及用量,优化后的外用制剂安全性更好,两者联合的治疗效果显著优于将颈痛颗粒和东方活血膏减半给药的效果,将其应用于临床治疗有望收获良好的治疗效果。(The invention particularly relates to a pharmaceutical composition, a preparation method thereof and application thereof in preparing a cervical spondylosis resisting medicine. In order to solve the problem of single action effect of the existing medicine, the invention aims to provide a treatment method for internal and external application, which realizes the shortening of the treatment period of the cervical spondylopathy of nerve roots and the reduction of the recurrence probability by simultaneously carrying out internal and external application. In order to realize the technical purpose, the invention optimizes the prior cervicodynia granules and the oriental blood circulation promoting ointment, the optimized external preparation has better safety by reasonably adjusting the medicine flavor and the dosage, the combined treatment effect of the cervicodynia granules and the oriental blood circulation promoting ointment is obviously superior to the effect of halving the administration of the cervicodynia granules and the oriental blood circulation promoting ointment, and the application of the cervicodynia granules and the oriental blood circulation promoting ointment in clinical treatment is expected to obtain good treatment effect.)

1. A pharmaceutical composition, which comprises the following ingredients: pseudo-ginseng, corydalis tuber, white paeony root, clematis root, kudzu-vine root, notopterygium root, dried ginger, safflower, szechuan lovage rhizome, rhizoma corydalis, frankincense (prepared), myrrh (prepared), twotooth achyranthes root, incised notopterygium rhizome, doubleteeth pubescent angelica root, Chinese angelica, turmeric, scorpion, dragon's blood, native copper, tall gastrodia tuber, dog bone, eucommia bark, cochinchina momordica seed, black fungus, realgar, alum, pepper, common cnidium fruit, costustoot, sandalwood, borneol, common clubmoss herb, honeysuckle flower, gypsum, catechu;

8-12 parts of pseudo-ginseng, 9-13 parts of ligusticum wallichii, 5-9 parts of corydalis tuber, 9-14 parts of radix paeoniae alba, 11-16 parts of radix clematidis, 9-16 parts of radix puerariae and 9-15 parts of notopterygium root are used for preparing oral preparations;

13-17 parts of dried ginger, 8-12 parts of safflower, 3-7 parts of ligusticum wallichii, 2-5 parts of rhizoma corydalis, 8-12 parts of prepared frankincense, 8-12 parts of prepared myrrh, 8-12 parts of achyranthes bidentata, 10-14 parts of notopterygium root, 9-13 parts of radix angelicae pubescentis, 10-14 parts of angelica sinensis, 5-8 parts of turmeric, 2-5 parts of scorpion, 2-5 parts of dragon's blood, 2-5 parts of native copper, 3-7 parts of gastrodia elata, 9-15 parts of dog bone, 9-13 parts of eucommia ulmoides, 5-9 parts of cochinchina momordica seed, 3-6 parts of black fungus, 6-10 parts of realgar, 6-10 parts of alum, 6-10 parts of pepper, 5-9 parts of fructus cnidii, 3-7 parts of elecampane, 5-9 parts of sandalwood, 10-14 parts of borneol, 10-14 parts of lycopodium clavatum, 10-14 parts of honeysuckle, 4-8 parts of gypsum, 6-10 parts of catechu, 1-3 parts of.

2. The pharmaceutical composition of claim 1, wherein the oral preparation includes but is not limited to oral liquid preparations such as decoction, suspension, syrup, mixture, tincture, etc., and can be ointment, granule, pill, powder, tablet, capsule, granule or drop;

or, the external preparation includes, but is not limited to, lotion, ointment, tincture, liniment, spirit, powder, oil, paste, plastics or aerosol;

preferably, the lotion comprises a solution type, a suspension type and an emulsion type;

preferably, the ointment comprises ointment, plaster, cream and gel.

3. The pharmaceutical composition of claim 1, wherein the oral medicament comprises the following ingredients in parts by weight: 10 parts of pseudo-ginseng, 11 parts of ligusticum wallichii, 7 parts of corydalis tuber, 12 parts of white paeony root, 14 parts of clematis root, 12 parts of kudzu root and 11 parts of notopterygium root;

or 8 parts of pseudo-ginseng, 9 parts of ligusticum wallichii, 5 parts of corydalis tuber, 9 parts of radix paeoniae alba, 11 parts of radix clematidis, 9 parts of radix puerariae and 9 parts of notopterygium root;

or 12 parts of pseudo-ginseng, 13 parts of ligusticum wallichii, 9 parts of corydalis tuber, 14 parts of radix paeoniae alba, 15 parts of radix clematidis, 16 parts of radix puerariae and 15 parts of notopterygium root.

4. The pharmaceutical composition of claim 1, wherein the oral preparation further comprises pharmaceutically necessary excipients, such as but not limited to fillers, disintegrants, wetting agents or binders; the filler is one or more of starch, sucrose, dextrin, calcium sulfate, calcium hydrogen phosphate, magnesium oxide, calcium carbonate, microcrystalline cellulose, mannitol and lactose; the disintegrant is one or more of dry starch, sodium carboxymethyl starch, hydroxypropyl cellulose, crospovidone and surfactant; the wetting agent is distilled water or ethanol; the adhesive is one or more of sugar powder, syrup, starch slurry and polyvinylpyrrolidone.

5. The pharmaceutical combination of claim 1, wherein the external preparation further comprises an emulsifier, stabilizer, preservative, antioxidant, flavoring or coloring agent;

the emulsifier comprises an oil phase emulsifier and a water phase emulsifier, the oil phase emulsifier comprises vaseline, lanolin and the like, and the water phase emulsifier comprises triethanolamine and glycerol; the preservative is one or more of but not limited to benzoic acid, sorbic acid, ethanol, paraben, propylene glycol and phenol; the antioxidant comprises a water-soluble antioxidant and an oil-soluble antioxidant, and the water-soluble antioxidant comprises sodium bisulfite, sodium metabisulfite, sodium sulfite, dry sodium sulfite, ascorbic acid, thiourea and phosphoric acid; the oil-soluble antioxidant comprises tert-butyl p-hydroxyanisole, tert-butyl p-cresol, nordihydroguaiaretic acid or tocopherol.

6. The process for preparing a pharmaceutical composition according to any one of claims 1 to 5, wherein the process for preparing comprises a process for preparing an oral preparation and a process for preparing an external preparation;

the preparation method of the oral preparation comprises the following steps: dividing Notoginseng radix into fine powder; extracting volatile oil from the notopterygium root and the clematis root by a steam distillation method, mixing the remained water decoction with the water decoction of the kudzuvine root and the white paeony root, and carrying out alcohol precipitation to obtain concentrated clear paste; extracting rhizoma Ligustici Chuanxiong and rhizoma corydalis with ethanol, and concentrating to obtain fluid extract; mixing the above two fluid extracts, Notoginseng radix powder and volatile oil, and adding adjuvants to obtain oral preparation;

the preparation method of the external preparation comprises the following steps: pulverizing Olibanum, Myrrha, Catechu, Alumen, Gypsum Fibrosum, Pyritum, Realgar, sanguis Draxonis, and Borneolum Syntheticum, and grinding into powder; adding alcohol solution into rhizoma Zingiberis, flos Carthami, rhizoma Chuanxiong, rhizoma corydalis, radix Achyranthis bidentatae, rhizoma Et radix Notopterygii, radix Angelicae Pubescentis, radix Angelicae sinensis, rhizoma Curcumae Longae, Scorpio, rhizoma Gastrodiae, Os Canitis, cortex Eucommiae, semen Momordicae, Auricularia, pericarpium Zanthoxyli, fructus Cnidii, radix aucklandiae, lignum Santali albi, herba Lycopodii, flos Lonicerae, and herba asari, reflux-extracting, concentrating the extractive solution to obtain extract, and adding semen Sinapis to the extract.

7. The method for preparing the pharmaceutical composition according to claim 6, wherein the method for preparing the oral preparation comprises the steps of combining the two fluid extracts, adding the pseudo-ginseng powder, mixing, adding a proper amount of dextrin, mixing uniformly, spraying the volatile oil, and tabletting to obtain an oral tablet;

preferably, in the preparation method of the oral preparation, the two clear pastes are combined, added with pseudo-ginseng powder, mixed with a proper amount of dextrin, mixed uniformly, added with a small amount of ethanol to form a mass, sieved and granulated, and sprayed with the notopterygium root and clematis root volatile oil after granules are dried to obtain the oral granules.

8. The method for preparing the pharmaceutical composition of claim 6, wherein in the method for preparing the external preparation, the prepared frankincense, the prepared myrrh, the catechu, the alum, the gypsum, the native copper, the realgar, the dragon's blood and the borneol are ground and sieved by a sieve of 130 to 150 meshes to obtain the pharmaceutical powder;

or in the preparation method of the external preparation, the alcoholic solution is a 65-75% ethanol solution with 2-4 times volume;

or, the external preparation is paste, and the preparation method comprises mixing the powder, extract and semen Sinapis Albae oil, adding glycerol, and mixing to obtain paste;

preferably, the white mustard oil and the extract are mixed to obtain an oil-phase medicament, the medicament powder is dissolved in triethanolamine to obtain a water-phase medicament, and the oil-phase medicament and the water-phase medicament are mixed to obtain the ointment;

preferably, the white mustard oil is added into the extract, a small amount of medicinal powder is mixed into the extract, and then the phenol solution is added to adjust the viscosity to obtain the ointment.

9. Use of the pharmaceutical combination of any one of claims 1 to 5 for the preparation of a product for the treatment of cervical spondylosis;

preferably, the cervical spondylosis is cervical spondylotic radiculopathy;

preferably, the application also comprises the application of the pharmaceutical composition in preparing foods, health products, medicines or cosmetics for treating or improving cervical spondylosis and pains thereof.

10. A method of treatment of cervical spondylotic radiculopathy, which comprises treatment with a pharmaceutical combination according to any one of claims 1 to 5;

preferably, the external preparation is applied to the affected part while the oral preparation is taken in the treatment mode.

Technical Field

The invention belongs to the technical field of medicaments for treating cervical spondylosis, and particularly relates to a medicament combination, a preparation method of the medicament combination and application of the medicament combination in preparing medicaments for resisting nerve roots and cervical spondylosis.

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 refers to the condition that the nerve root is compressed and the innervated area is painful, numb, sensory loss and reflex change to some extent due to the degeneration of cervical vertebra. The main symptom of cervical spondylotic radiculopathy is radicular pain. Nerve roots are more susceptible to various mechanical factors than peripheral nerves. The main reason is that the amount and arrangement of the connective tissue around it are different from those of the peripheral nerves. Nerve fibers within a typical nerve root are arranged in parallel with no dense connective tissue therebetween and are therefore more susceptible to traction. In addition, the nerve roots are not protected by the nerve adventitia and are more easily damaged by pressure. The cervical spinal root ganglion is a special part of the spinal nerve, with the cell bodies of the sensory neurons. Cervical root ganglia are sensitive to mechanical stimulation and it is critical that the ganglia be stressed by a herniated disc, hypertrophic ligament or osteophyte to produce a root symptom. Cervical root ganglia are present in intervertebral foramina, and the radicular pain is mainly caused by mechanical compression caused by intervertebral disc diseases or intervertebral foramina stenosis which involve intervertebral foramina, and can also be caused by pain generators whose periphery is involved by nerve root diseases. Pain is caused by stimulation of demyelinated slow-conducting nerve fibers, i.e., C-fibers. The C fibers accompany the peripheral nerve roots, causing the cervical root ganglia to release neurotransmitters and nerve impulses to travel up the spinothalamic tract on the contralateral dorsal lateral side to the thalamus and then to the cerebral cortex, producing radicular pain. At present, the understanding of the pathophysiology of the radicular cervical spondylosis in the field is mainly based on the study on the lumbar disc pathology and the nerve injury of animals and human beings, but the pathogenesis of the radicular cervical spondylosis is not completely clear.

The existing treatment method for the cervical spondylotic radiculopathy comprises two modes of internal administration and external application, wherein the internal administration mainly adopts internal treatment medicines, and the external application mainly adopts external medicines, massage or acupuncture and moxibustion and the like. Because the cervical spondylotic radiculopathy belongs to degenerative diseases, the cervical spondylotic radiculopathy is good for the old. According to the traditional Chinese medicine, the liver governs tendons, the kidney governs bones, and the liver and kidney govern the movement function of the human body. The traditional Chinese medicine has advantages in the treatment of the cervical spondylotic radiculopathy, and the traditional Chinese medicine can give consideration to the whole and local parts by combining the mode of oral administration and external treatment, so that the aim of quickly eliminating symptoms is fulfilled.

Disclosure of Invention

Based on the technical background, the invention aims to provide a treatment scheme, and solves the problem that the existing medicine has single effect on the cervical spondylotic radiculopathy. Therefore, the invention provides a treatment mode of internal and external concurrent treatment, which can shorten the treatment period of the cervical spondylotic radiculopathy, reduce the recurrence probability and enhance the treatment effect of the cervical spondylopathy.

Based on the technical effects, the invention provides the following technical scheme:

in a first aspect of the present invention, a pharmaceutical composition is provided, which comprises the following ingredients: pseudo-ginseng, corydalis tuber, white paeony root, clematis root, kudzu-vine root, notopterygium root, dried ginger, safflower, szechuan lovage rhizome, rhizoma corydalis, frankincense (prepared), myrrh (prepared), twotooth achyranthes root, incised notopterygium rhizome, doubleteeth pubescent angelica root, Chinese angelica, turmeric, scorpion, dragon's blood, native copper, tall gastrodia tuber, dog bone, eucommia bark, cochinchina momordica seed, black fungus, realgar, alum, pepper, common cnidium fruit, costustoot, sandalwood, borneol, common clubmoss herb, honeysuckle flower, gypsum, catechu;

8-12 parts of pseudo-ginseng, 9-13 parts of ligusticum wallichii, 5-9 parts of corydalis tuber, 9-14 parts of radix paeoniae alba, 11-16 parts of radix clematidis, 9-16 parts of radix puerariae and 9-15 parts of notopterygium root are used for preparing oral preparations;

13-17 parts of dried ginger, 8-12 parts of safflower, 3-7 parts of ligusticum wallichii, 2-5 parts of rhizoma corydalis, 8-12 parts of frankincense (prepared), 8-12 parts of myrrh (prepared), 8-12 parts of achyranthes bidentata, 10-14 parts of notopterygium root, 9-13 parts of radix angelicae pubescentis, 10-14 parts of angelica sinensis, 5-8 parts of turmeric, 2-5 parts of scorpion, 2-5 parts of dragon's blood, 2-5 parts of native copper, 3-7 parts of gastrodia elata, 9-15 parts of dog bone, 9-13 parts of eucommia ulmoides, 5-9 parts of cochinchina momordica seed, 3-6 parts of black fungus, 6-10 parts of realgar, 6-10 parts of alum, 6-10 parts of pepper, 5-9 parts of fructus cnidii, 3-7 parts of elecampane, 5-9 parts of sandalwood, 10-14 parts of borneol, 10-14 parts of lycopodium clavatum, 10-14 parts of honeysuckle, 4-8 parts of gypsum, 6-10 parts of catechu, 1-3 parts of asarum.

The patent CN105250933B provides a traditional Chinese medicine composition with the effects of activating blood and dissolving stasis, namely an oriental blood-activating plaster, which has good treatment effect on various symptoms of anemofrigid-damp arthralgia. However, the raw aconite and kusnezoff monkshood root of the above drugs have certain toxicity, and the toxicity of the drugs needs to be removed by processing methods such as long-term decoction. The oriental blood circulation promoting plaster is used as a traditional black plaster, the traditional Chinese medicine materials are fried in oil in the preparation process, the toxicity of the raw radix aconiti and the raw radix aconiti agrestis can be effectively removed by the high-temperature processing method, but the cleaning of the lead plaster in the black plaster is difficult after the lead plaster is used, lead ions have certain adverse effect on human bodies, the air permeability of the rubber adhesive plaster is poor, and the sensitization rate is high.

The invention designs a medicine combination form for oral administration and external use, thereby optimizing the oriental blood circulation promoting ointment and being suitable for treating the cervical spondylotic radiculopathy. The inventor removes raw radix aconiti and raw radix aconiti kusnezoffii which may have toxicity in the optimized medicine formula, removes the national regulated medicine pangolin, adds the dried ginger with lower cost in the optimized medicine formula, increases the effect of warming middle-jiao and dispelling cold, and simultaneously properly adjusts the medicinal taste composition of the original cervicodynia granules. According to the experimental result, the pain symptoms before and after the administration are obviously different, which shows that the product of the invention has the functions of dispelling wind and clearing heat, detoxifying and resolving masses, and activating blood and dissolving stasis, and has obvious curative effects on treating and promoting recovery of cervical spondylosis. In addition, the invention adopts a method of internal and external simultaneous treatment, can shorten the treatment period of cervical spondylosis and enhance the treatment effect of cervical spondylosis. The external product and the internal product of the invention can be used independently, and can also be used in combination in any proportion.

In a second aspect of the present invention, a method for preparing the pharmaceutical composition of the first aspect is provided, wherein the method for preparing the pharmaceutical composition comprises a method for preparing an oral preparation and a method for preparing an external preparation;

the preparation method of the oral preparation comprises the following steps: dividing Notoginseng radix into fine powder; extracting volatile oil from the notopterygium root and the clematis root by a steam distillation method, mixing the remained water decoction with the water decoction of the kudzuvine root and the white paeony root, and carrying out alcohol precipitation to obtain concentrated clear paste; extracting rhizoma Ligustici Chuanxiong and rhizoma corydalis with ethanol, and concentrating to obtain fluid extract; mixing the above two fluid extracts, Notoginseng radix powder and volatile oil, and adding adjuvants to obtain oral preparation;

the preparation method of the external preparation comprises the following steps: pulverizing Olibanum (preparata), Myrrha (preparata), Catechu, Alumen, Gypsum Fibrosum, Pyritum, Realgar, sanguis Draxonis, and Borneolum Syntheticum, and grinding into powder; adding alcohol solution into rhizoma Zingiberis, flos Carthami, rhizoma Chuanxiong, rhizoma corydalis, radix Achyranthis bidentatae, rhizoma Et radix Notopterygii, radix Angelicae Pubescentis, radix Angelicae sinensis, rhizoma Curcumae Longae, Scorpio, rhizoma Gastrodiae, Os Canitis, cortex Eucommiae, semen Momordicae, Auricularia, pericarpium Zanthoxyli, fructus Cnidii, radix aucklandiae, lignum Santali albi, herba Lycopodii, flos Lonicerae, and herba asari, reflux-extracting, concentrating the extractive solution to obtain extract, and adding semen Sinapis to the extract.

In the optimized preparation method, the effective components in the external preparation are extracted by an alcohol extraction mode, the preparation process is simple, the extraction effect is more sufficient compared with an oil-decocting mode, the prepared medicine is preferably a paste, and the defects of the traditional black paste are overcome.

In a third aspect of the present invention, an application of the pharmaceutical composition of the first aspect in preparing a medicament for resisting cervical spondylosis is provided.

In a fourth aspect of the invention, there is provided a method of treatment of cervical spondylotic radiculopathy, said method of treatment comprising treatment with a combination of drugs according to the first aspect.

The beneficial effects of one or more technical schemes are as follows:

the invention conjectures that the external medicine is used for treating cervical spondylotic radiculopathy, and provides an internal and external treatment mode by combining with internal medicines. The oriental blood circulation promoting plaster is used for treating joint swelling and pain caused by rheumatism, and the monarch drugs including raw radix aconiti and raw radix aconiti agrestis in the formula have good effects of dispelling wind and removing dampness, warming channels and relieving pain. The regulated medicinal composition omits toxic medicinal materials such as raw radix aconiti, raw radix aconiti agrestis and the like, adds the dried ginger with lower cost, and removes national regulated medicaments such as pangolin scales and the like. The total cost of the medicine is lower, however, the experimental result shows that the effect of the medicine combination is obviously better than the combined treatment effect of the oriental blood circulation promoting ointment and the neck pain granules. Meanwhile, the external preparation provided by the invention is safer to use.

Detailed Description

It is to be understood that the following detailed description is exemplary and is intended to provide further explanation of the invention as claimed. 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 to which this invention belongs.

It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of exemplary embodiments according to the invention. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, and it should be understood that when the terms "comprises" and/or "comprising" are used in this specification, they specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof, unless the context clearly indicates otherwise.

As described in the background, in order to solve the above technical problems, the present invention proposes a pharmaceutical composition for treating cervical spondylotic radiculopathy.

In a first aspect of the present invention, a pharmaceutical composition is provided, which comprises the following ingredients: pseudo-ginseng, corydalis tuber, white paeony root, clematis root, kudzu-vine root, notopterygium root, dried ginger, safflower, szechuan lovage rhizome, rhizoma corydalis, frankincense (prepared), myrrh (prepared), twotooth achyranthes root, incised notopterygium rhizome, doubleteeth pubescent angelica root, Chinese angelica, turmeric, scorpion, dragon's blood, native copper, tall gastrodia tuber, dog bone, eucommia bark, cochinchina momordica seed, black fungus, realgar, alum, pepper, common cnidium fruit, costustoot, sandalwood, borneol, common clubmoss herb, honeysuckle flower, gypsum, catechu;

8-12 parts of pseudo-ginseng, 9-13 parts of ligusticum wallichii, 5-9 parts of corydalis tuber, 9-14 parts of radix paeoniae alba, 11-16 parts of radix clematidis, 9-16 parts of radix puerariae and 9-15 parts of notopterygium root are used for preparing oral preparations;

13-17 parts of dried ginger, 8-12 parts of safflower, 3-7 parts of ligusticum wallichii, 2-5 parts of rhizoma corydalis, 8-12 parts of frankincense (prepared), 8-12 parts of myrrh (prepared), 8-12 parts of achyranthes bidentata, 10-14 parts of notopterygium root, 9-13 parts of radix angelicae pubescentis, 10-14 parts of angelica sinensis, 5-8 parts of turmeric, 2-5 parts of scorpion, 2-5 parts of dragon's blood, 2-5 parts of native copper, 3-7 parts of gastrodia elata, 9-15 parts of dog bone, 9-13 parts of eucommia ulmoides, 5-9 parts of cochinchina momordica seed, 3-6 parts of black fungus, 6-10 parts of realgar, 6-10 parts of alum, 6-10 parts of pepper, 5-9 parts of fructus cnidii, 3-7 parts of elecampane, 5-9 parts of sandalwood, 10-14 parts of borneol, 10-14 parts of lycopodium clavatum, 10-14 parts of honeysuckle, 4-8 parts of gypsum, 6-10 parts of catechu, 1-3 parts of asarum.

Preferably, the oral preparation includes, but is not limited to, oral liquid preparations such as decoction, suspension, syrup, mixture, tincture and the like, and can also be prepared into paste, granules, pills (honeyed pills, water pills, paste pills, wax pills and concentrated pills), powder, tablets (enteric-coated tablets, film-coated tablets, sugar-coated tablets, extract tablets, dispersible tablets, scratch tablets), capsules, granules, drops and the like.

Preferably, the external preparation includes, but is not limited to, lotion, ointment, tincture, liniment, spirit, powder, oil, paste, plastics, aerosol, etc.

Further, the lotion comprises a solution type, a suspension type and an emulsion type.

Further, the ointment comprises ointment, plaster, cream and gel.

The oral preparation and the external preparation are prepared according to the conventional preparation method in the field, and the selection of different auxiliary materials in the preparation form has no significant influence on the curative effect of the medicine. In some embodiments with better effects, the oral medicament comprises the following medicinal ingredients in parts by weight: 10 parts of pseudo-ginseng, 11 parts of ligusticum wallichii, 7 parts of corydalis tuber, 12 parts of white paeony root, 14 parts of clematis root, 12 parts of kudzu root and 11 parts of notopterygium root;

or 8 parts of pseudo-ginseng, 9 parts of ligusticum wallichii, 5 parts of corydalis tuber, 9 parts of radix paeoniae alba, 11 parts of radix clematidis, 9 parts of radix puerariae and 9 parts of notopterygium root;

or 12 parts of pseudo-ginseng, 13 parts of ligusticum wallichii, 9 parts of corydalis tuber, 14 parts of radix paeoniae alba, 15 parts of radix clematidis, 16 parts of radix puerariae and 15 parts of notopterygium root.

The oral preparation also comprises pharmaceutically necessary auxiliary materials, wherein the auxiliary materials comprise but are not limited to a filling agent, a disintegrating agent, a wetting agent or a binding agent and the like; the filler is one or more of starch, sucrose, dextrin, calcium sulfate, calcium hydrogen phosphate, magnesium oxide, calcium carbonate, microcrystalline cellulose, mannitol and lactose; the disintegrant is one or more of dry starch, sodium carboxymethyl starch, hydroxypropyl cellulose, crospovidone and surfactant; the wetting agent is distilled water or ethanol; the adhesive is one or more of sugar powder, syrup, starch slurry and polyvinylpyrrolidone.

The external preparation also comprises an emulsifier, a stabilizer, a preservative, an antioxidant, a flavoring agent or a coloring agent and the like. The emulsifier comprises an oil phase emulsifier and a water phase emulsifier, the oil phase emulsifier comprises vaseline, lanolin and the like, and the water phase emulsifier comprises triethanolamine and glycerol; the preservative is one or more of benzoic acid, sorbic acid, ethanol, paraben, propylene glycol and phenol. The antioxidant comprises a water-soluble antioxidant and an oil-soluble antioxidant, and the water-soluble antioxidant comprises sodium bisulfite, sodium metabisulfite, sodium sulfite, dry sodium sulfite, ascorbic acid, thiourea, phosphoric acid and the like; the oil-soluble antioxidant comprises tert-butyl p-hydroxyanisole, tert-butyl p-cresol, nordihydroguaiaretic acid or tocopherol, etc.

In a second aspect of the present invention, a method for preparing the pharmaceutical composition of the first aspect is provided, wherein the method for preparing the pharmaceutical composition comprises a method for preparing an oral preparation and a method for preparing an external preparation;

the preparation method of the oral preparation comprises the following steps: dividing Notoginseng radix into fine powder; extracting volatile oil from the notopterygium root and the clematis root by a steam distillation method, mixing the remained water decoction with the water decoction of the kudzuvine root and the white paeony root, and carrying out alcohol precipitation to obtain concentrated clear paste; extracting rhizoma Ligustici Chuanxiong and rhizoma corydalis with ethanol, and concentrating to obtain fluid extract; mixing the above two fluid extracts, Notoginseng radix powder and volatile oil, and adding adjuvants to obtain oral preparation;

the preparation method of the external preparation comprises the following steps: pulverizing Olibanum (preparata), Myrrha (preparata), Catechu, Alumen, Gypsum Fibrosum, Pyritum, Realgar, sanguis Draxonis, and Borneolum Syntheticum, and grinding into powder; adding alcohol solution into rhizoma Zingiberis, flos Carthami, rhizoma Chuanxiong, rhizoma corydalis, radix Achyranthis bidentatae, rhizoma Et radix Notopterygii, radix Angelicae Pubescentis, radix Angelicae sinensis, rhizoma Curcumae Longae, Scorpio, rhizoma Gastrodiae, Os Canitis, cortex Eucommiae, semen Momordicae, Auricularia, pericarpium Zanthoxyli, fructus Cnidii, radix aucklandiae, lignum Santali albi, herba Lycopodii, flos Lonicerae, and herba asari, reflux-extracting, concentrating the extractive solution to obtain extract, and adding semen Sinapis to the extract.

Preferably, in the preparation method of the oral preparation, the two clear pastes are combined, added with pseudo-ginseng powder, mixed with a proper amount of dextrin, mixed uniformly, sprayed with the volatile oil and tableted to obtain an oral tablet.

Preferably, in the preparation method of the oral preparation, the two clear pastes are combined, added with pseudo-ginseng powder, mixed with a proper amount of dextrin, mixed uniformly, added with a small amount of ethanol to form a mass, sieved and granulated, and sprayed with the notopterygium root and clematis root volatile oil after granules are dried to obtain the oral granules.

Preferably, in the preparation method of the external preparation, the frankincense (prepared), the myrrh (prepared), the catechu, the alum, the gypsum, the native copper, the realgar, the dragon's blood and the borneol are ground and sieved by a sieve of 130-150 meshes to obtain the medicine powder.

Preferably, in the preparation method of the external preparation, the alcohol solution is a 65-75% ethanol solution with 2-4 times volume.

Preferably, the external preparation is paste, and the preparation method comprises mixing the powder, extract and white mustard seed oil, adding glycerol, and mixing to obtain paste;

or mixing the white mustard oil and the extract to obtain an oil-phase medicament, dissolving the medicament powder in triethanolamine to obtain a water-phase medicament, and mixing the oil-phase medicament and the water-phase medicament to obtain the ointment;

or adding the white mustard oil into the extract, mixing a small amount of the medicinal powder into the extract, and adding a phenol solution to adjust the viscosity to obtain the paste.

In a third aspect of the invention, the application of the pharmaceutical composition of the first aspect in preparing a product for resisting cervical spondylosis is provided.

Preferably, the cervical spondylosis is cervical spondylotic radiculopathy.

Preferably, the invention also provides application of the pharmaceutical composition in preparing foods, health products, medicines or cosmetics for treating or improving cervical spondylosis and pains thereof.

In a fourth aspect of the invention, there is provided a method of treatment of cervical spondylotic radiculopathy, said method of treatment comprising treatment with a combination of drugs according to the first aspect.

Preferably, the external preparation is applied to the affected part while the oral preparation is taken in the treatment mode.

In order to make the technical solutions of the present invention more clearly understood by those skilled in the art, the technical solutions of the present invention will be described in detail below with reference to specific embodiments.

Example 1

In the embodiment, the treatment medicine for treating the cervical spondylotic radiculopathy comprises an oral medicine and an external application medicine, wherein the oral medicine comprises the following medicines in parts by weight: 10 parts of pseudo-ginseng, 11 parts of ligusticum wallichii, 7 parts of corydalis tuber, 12 parts of white paeony root, 14 parts of clematis root, 12 parts of kudzu root and 11 parts of notopterygium root.

The preparation method of the oral medicine comprises the following steps:

(1) firstly, grinding pseudo-ginseng into fine powder of 110 meshes;

(2) extracting volatile oil from Notopterygii rhizoma and radix Clematidis, collecting the distilled water solution in another container, decocting the residue with water for 1 hr, and filtering to obtain filtrate;

(3) decocting radix Puerariae and radix Paeoniae alba with water twice (2 hr for the first time and 1 hr for the second time), mixing the filtrate with the above two water solutions, concentrating, precipitating with ethanol, recovering ethanol, and concentrating to obtain fluid extract with relative density of 1.25(50 deg.C);

(4) 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 1.30(50 deg.C);

(5) mixing the above two fluid extracts, adding Notoginseng radix powder, mixing, drying, pulverizing into fine powder, adding appropriate amount of dextrin, mixing, spraying the volatile oil of Notopterygii rhizoma and radix Clematidis, and tabletting.

The using method comprises the following steps: it is taken 4 tablets at a time 3 times a day after meals.

The external application medicine comprises the following medicinal ingredients in parts by weight: 15 parts of dried ginger, 10 parts of safflower, 5 parts of szechuan lovage rhizome, 3 parts of rhizoma corydalis, 10 parts of frankincense (prepared), 10 parts of myrrh (prepared), 10 parts of twotooth achyranthes root, 12 parts of incised notopterygium rhizome, 11 parts of doubleteeth pubescent angelica root, 12 parts of Chinese angelica, 6 parts of turmeric, 3 parts of scorpion, 3 parts of dragon's blood, 3 parts of native copper, 5 parts of tall gastrodia tuber, 11 parts of dog bone, 11 parts of eucommia bark, 7 parts of cochinchina momordica seed, 4 parts of black fungus, 8 parts of realgar, 8 parts of alum, 8 parts of pepper, 7 parts of common cnidium fruit, 5 parts of costustoot, 7 parts of sandalwood, 12 parts of borneol, 12 parts of common clubmoss herb, 12 parts of honeysuckle flower, 6 parts.

The preparation method of the externally applied medicine comprises the following steps:

(1) pulverizing Olibanum (preparata), Myrrha (preparata), Catechu, Alumen, Gypsum Fibrosum, Pyritum, Realgar, sanguis Draxonis, and Borneolum Syntheticum, grinding, and sieving with 150 mesh sieve to obtain powder;

(2) adding rhizoma Zingiberis, flos Carthami, rhizoma Chuanxiong, rhizoma corydalis, radix Achyranthis bidentatae, rhizoma Et radix Notopterygii, radix Angelicae Pubescentis, radix Angelicae sinensis, rhizoma Curcumae Longae, Scorpio, rhizoma Gastrodiae, Os Canitis, cortex Eucommiae, semen Momordicae, Auricularia, pericarpium Zanthoxyli, fructus Cnidii, radix aucklandiae, lignum Santali albi, herba Lycopodii, flos Lonicerae, and herba asari into 70% ethanol solution 3 times the volume of which is added to perform reflux extraction for 40min, repeating extraction for three times, mixing filtrates, and concentrating under reduced pressure to obtain an extract with a density of 1.20 (measured at 80 ℃).

(3) Adding the white mustard oil into the extract obtained in the step (2), melting the extract into uniform paste, adding a small amount of the powder obtained in the step (1) into the paste for multiple times, and adding a proper amount of glycerin according to the thickening condition of the paste for adjustment.

The using method comprises the following steps: the ointment is applied to the affected part 1-2 times per day.

Example 2

In the embodiment, the treatment medicine for treating the cervical spondylotic radiculopathy comprises an oral medicine and an external application medicine, wherein the oral medicine comprises the following medicines in parts by weight: 8 parts of pseudo-ginseng, 9 parts of ligusticum wallichii, 5 parts of corydalis tuber, 9 parts of white paeony root, 11 parts of clematis root, 9 parts of kudzu root and 9 parts of notopterygium root.

The preparation method of the oral medicine comprises the following steps:

(1) firstly, grinding the pseudo-ginseng into fine powder of 100 meshes;

(2) extracting volatile oil from Notopterygii rhizoma and radix Clematidis, collecting the distilled water solution in another container, decocting the residue with water for 0.8 hr, and filtering to obtain filtrate;

(3) decocting radix Puerariae and radix Paeoniae alba with water twice, the first time for 1.5 hr and the second time for 0.8 hr, mixing the filtrate with the above two water solutions, concentrating, precipitating with ethanol, recovering ethanol, and concentrating to obtain fluid extract with relative density of 1.30(50 deg.C);

(4) 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(50 deg.C);

(5) mixing the above fluid extracts and Notoginseng radix powder, adding appropriate amount of dextrin, mixing with 95 alcohol to obtain a ball, sieving, granulating, and spraying the volatile oil of Notopterygii rhizoma and radix Clematidis to obtain granule.

The using method comprises the following steps: the medicine is taken 8-10 g at a time 3 times a day after meals.

The external application medicine comprises the following medicinal ingredients in parts by weight: 13 parts of dried ginger, 8 parts of safflower, 3 parts of szechuan lovage rhizome, 2 parts of rhizoma corydalis, 8 parts of frankincense (prepared), 8 parts of myrrh (prepared), 8 parts of twotooth achyranthes root, 10 parts of incised notopterygium rhizome, 9 parts of pubescent angelica root, 10 parts of Chinese angelica, 5 parts of turmeric, 2 parts of scorpion, 2 parts of dragon's blood, 2 parts of native copper, 3 parts of tall gastrodia tuber, 9 parts of dog bone, 9 parts of eucommia bark, 5 parts of cochinchina momordica seed, 3 parts of black fungus, 6 parts of realgar, 6 parts of alum, 6 parts of pepper, 5 parts of common cnidium fruit, 3 parts of costustoot, 5 parts of sandalwood, 10 parts of borneol, 10 parts of common clubmoss herb, 10 parts of honeysuckle flower, 4 parts of gypsum, 6.

The preparation method of the externally applied medicine comprises the following steps:

(1) pulverizing Olibanum (preparata), Myrrha (preparata), Catechu, Alumen, Gypsum Fibrosum, Pyritum, Realgar, sanguis Draxonis, and Borneolum Syntheticum, grinding, and sieving with 130 mesh sieve to obtain powder;

(2) adding rhizoma Zingiberis, flos Carthami, rhizoma Chuanxiong, rhizoma corydalis, radix Achyranthis bidentatae, rhizoma Et radix Notopterygii, radix Angelicae Pubescentis, radix Angelicae sinensis, rhizoma Curcumae Longae, Scorpio, rhizoma Gastrodiae, Os Canitis, cortex Eucommiae, semen Momordicae, Auricularia, pericarpium Zanthoxyli, fructus Cnidii, radix aucklandiae, lignum Santali albi, herba Lycopodii, flos Lonicerae, and herba asari into a 4-fold volume of 65% ethanol solution, reflux-extracting for 50min, repeating the extraction for three times, mixing filtrates, and concentrating under reduced pressure to obtain an extract with a density of 1.25(80 deg.C).

(3) Adding white mustard oil into the extract obtained in the step (2), melting the extract into uniform paste, dissolving the powder obtained in the step (1) into triethanolamine, adding the triethanolamine medicinal solution into the ointment, and adding a proper amount of vaseline or lanolin according to the viscosity condition of the ointment for adjustment. The using method comprises the following steps: the ointment is applied to the affected part 1-2 times per day.

Example 3

In the embodiment, the treatment medicine for treating the cervical spondylotic radiculopathy comprises an oral medicine and an external application medicine, wherein the oral medicine comprises the following medicines in parts by weight: 12 parts of pseudo-ginseng, 13 parts of ligusticum wallichii, 9 parts of corydalis tuber, 14 parts of white paeony root, 15 parts of clematis root, 16 parts of kudzu root and 15 parts of notopterygium root.

The preparation method of the oral medicine comprises the following steps:

(1) firstly, grinding pseudo-ginseng into fine powder of 120 meshes;

(2) extracting volatile oil from Notopterygii rhizoma and radix Clematidis, collecting the distilled water solution in another container, decocting the residue with water for 0.8 hr, and filtering to obtain filtrate;

(3) decocting radix Puerariae and radix Paeoniae alba with water twice (2.5 hr for the first time and 1.2 hr for the second time), mixing the filtrate with the above two water solutions, concentrating, precipitating with ethanol, recovering ethanol, and concentrating to obtain fluid extract with relative density of 1.35(50 deg.C);

(4) 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 1.35(50 deg.C);

(5) mixing the above two fluid extracts, adding Notoginseng radix powder, mixing, drying, pulverizing into fine powder, adding appropriate amount of dextrin, mixing, spraying the volatile oil of Notopterygii rhizoma and radix Clematidis, and tabletting.

The using method comprises the following steps: it is taken 4 tablets at a time 3 times a day after meals.

The external application medicine comprises the following medicinal ingredients in parts by weight: 17 parts of dried ginger, 12 parts of safflower, 7 parts of szechuan lovage rhizome, 5 parts of rhizoma corydalis, 12 parts of frankincense (prepared), 12 parts of myrrh (prepared), 12 parts of twotooth achyranthes root, 14 parts of incised notopterygium rhizome, 13 parts of pubescent angelica root, 14 parts of Chinese angelica, 8 parts of turmeric, 5 parts of scorpion, 5 parts of dragon's blood, 5 parts of native copper, 7 parts of tall gastrodia tuber, 15 parts of dog bone, 13 parts of eucommia bark, 9 parts of cochinchina momordica seed, 6 parts of black fungus, 10 parts of realgar, 10 parts of alum, 10 parts of pepper, 9 parts of common cnidium fruit, 7 parts of costustoot, 9 parts of sandalwood, 14 parts of borneol, 14 parts of common clubmoss herb, 14 parts of honeysuckle flower, 8 parts of gypsum.

The preparation method of the externally applied medicine comprises the following steps:

(1) pulverizing Olibanum (preparata), Myrrha (preparata), Catechu, Alumen, Gypsum Fibrosum, Pyritum, Realgar, sanguis Draxonis, and Borneolum Syntheticum, grinding, and sieving with 130 mesh sieve to obtain powder;

(2) adding rhizoma Zingiberis, flos Carthami, rhizoma Chuanxiong, rhizoma corydalis, radix Achyranthis bidentatae, rhizoma Et radix Notopterygii, radix Angelicae Pubescentis, radix Angelicae sinensis, rhizoma Curcumae Longae, Scorpio, rhizoma Gastrodiae, Os Canitis, cortex Eucommiae, semen Momordicae, Auricularia, pericarpium Zanthoxyli, fructus Cnidii, radix aucklandiae, lignum Santali albi, herba Lycopodii, flos Lonicerae, and herba asari into a 4-fold volume of 65% ethanol solution, reflux-extracting for 50min, repeating the extraction for three times, mixing filtrates, and concentrating under reduced pressure to obtain an extract with a density of 1.25(80 deg.C).

(3) Adding the white mustard oil into the extract obtained in the step (2), melting the extract into a uniform paste, adding a small amount of the powder obtained in the step (1) into the paste for multiple times, and adding a proper amount of 0.5% phenol solution for adjustment according to the thickening condition of the paste. The using method comprises the following steps: the ointment is applied to the affected part 1-2 times per day.

Example 4

First, safety verification

The preparation method comprises the steps of preparing two clear pastes and pseudo-ginseng powder according to the medicine proportion of 8 parts of pseudo-ginseng, 9 parts of ligusticum wallichii, 5 parts of corydalis tuber, 9 parts of white paeony root, 11 parts of clematis root, 9 parts of kudzu-vine root and 9 parts of notopterygium root in the mode recorded in the embodiment 1, and directly mixing the two clear pastes and the pseudo-ginseng powder to prepare the suspension with the maximum gavage concentration of 4.0 mg/mL. The daily gavage dosage is 4ml, and the gavage is completed in two times within 12 hours.

Weighing 15 parts of dried ginger, 10 parts of safflower, 5 parts of ligusticum wallichii, 3 parts of rhizoma corydalis, 10 parts of frankincense (prepared), 10 parts of myrrh (prepared), 10 parts of achyranthes bidentata, 12 parts of notopterygium root, 11 parts of radix angelicae pubescentis, 12 parts of angelica sinensis, 6 parts of turmeric, 3 parts of scorpion, 3 parts of dragon's blood, 3 parts of native copper, 5 parts of gastrodia elata, 11 parts of dog bone, 11 parts of eucommia ulmoides, 7 parts of cochinchina momordica seed, 4 parts of black fungus, 8 parts of realgar, 8 parts of alum, 8 parts of pepper, 7 parts of fructus cnidii, 5 parts of elecampane, 7 parts of sandalwood, 12 parts of borneol, 12 parts of lycopodium clavatum, 12 parts of honeysuckle, 6 parts of gypsum, 8 parts of catechu, 2 parts of asarum and 2 parts of.

Selecting 180-220 g SD rats, shaving 1.5 multiplied by 1.5cm of hair behind the neck of the SD rats to expose the skin surface of the SD rats, smearing the externally applied medicine on the exposed skin, simultaneously performing intragastric administration on the externally applied medicine, and continuously administering for 7 days according to the mode. Within 7 days after administration, rats observed normal diet and behavior activities, smooth hair, good glossiness, sensitive response, lively and well-moving, stable respiration and daily weight increase. At 8d, the rats are sacrificed, gross anatomy and pathological histology examination are carried out, and the pathology of the main organs is observed, so that no abnormality is found, which indicates that the oral administration and external application medicines provided by the invention have no adverse effect on animal organisms when being used together.

Second, analysis of therapeutic effects

1.1 therapeutic Standard

The judgment is made according to the 'evaluation of the curative effect of cervical spondylosis based on the standard of the diagnosis curative effect of the traditional Chinese medicine diseases' of the State administration of traditional Chinese medicine. And (3) curing: the symptoms disappear, the muscle strength is normal, the functions of the neck and the limbs are recovered to be normal, and the normal work and the work can be participated; improvement: the symptoms are reduced, the pain of the neck, the shoulder and the back is reduced, and the functions of the neck and the limbs are improved; and (4) invalidation: no improvement in symptoms.

Experimental group (300 cases): the oral medication and the external application medication prepared in example 1 were used for treatment, the external application medication being used twice daily.

Control 1(150 cases): the granule for relieving cervicodynia is taken orally one bag each time, 3 times a day, and half an hour after meal.

Control 2(150 cases): the oriental blood circulation promoting ointment is externally applied, is prepared according to the method described in the patent CN105250933B in the example 1, is heated and softened, is applied to an affected part, and is changed once a week.

Control group 3(150 cases): the oriental blood circulation promoting paste is externally applied while the cervicodynia granules are taken orally, the dosage of the oriental blood circulation promoting paste is halved compared with that of the control group 2, and the dosage of the cervicodynia granules is 0.5 bag each time.

The results of the one month treatment with the above-mentioned regimen are shown in the following table:

TABLE 1

Group of	N	Cure of disease	Improvement of life	Invalidation	Recurrence of disease	Adverse symptoms
							Treatment group	300	212	76	12	2	2
Control group 1	150	20	55	75	70	4
							Control group 2	150	26	31	93	83	19
Control group 3	150	86	34	30	52	12

The effective rate is (cure + improvement)/the total people is x%, and the treatment effects of the three groups are shown in the following table 2:

TABLE 2

Group of	Effective rate%	The recurrence rate%
			Treatment group	96	0.67
Control group 1	50	46.67
			Control group 2	38	55.3
Control group 3	80	34.67

The treatment results show that the effective rate of the oral and external application treatment method is obviously higher than that of other control groups, and the oral and external application medicine combination treatment has better treatment effect. Compared with the pure oral medicine and the pure external medicine, or the combination of the traditional neck pain granules and the oriental blood circulation promoting ointment by halving the dosage is not as good as the treatment effect of the invention.

In addition, in the treatment group and the control group 1, a small number of patients developed rashes during the treatment period and disappeared by themselves after the withdrawal of the drug. In contrast groups 2 and 3, some patients in the process of externally applying the oriental blood circulation promoting ointment have obvious allergy to lead in the rubber patch and the black plaster, so that the patients cannot continuously take the ointment, and the allergy phenomenon of the patients to the externally applied ointment is not found in the treatment group. As can be seen from the above table, the present invention has an overall superior therapeutic effect in treating cervical spondylotic radiculopathy and pain thereof, compared to the control group.

The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.