WO2022016827A1 - 一种神经再生复方制剂及其制备方法和用途 - Google Patents

一种神经再生复方制剂及其制备方法和用途 Download PDF

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WO2022016827A1
WO2022016827A1 PCT/CN2021/070266 CN2021070266W WO2022016827A1 WO 2022016827 A1 WO2022016827 A1 WO 2022016827A1 CN 2021070266 W CN2021070266 W CN 2021070266W WO 2022016827 A1 WO2022016827 A1 WO 2022016827A1
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parts
compound preparation
preparation
servings
fried
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French (fr)
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顾晓松
汤淳康
丁斐
杨晓明
程琼
孙华林
徐来
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Nantong University
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Nantong University
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Priority to EP21845721.6A priority Critical patent/EP4082556B1/en
Priority to US17/790,646 priority patent/US12115204B2/en
Priority to KR1020227025335A priority patent/KR102957466B1/ko
Priority to JP2022523397A priority patent/JP7498983B2/ja
Publication of WO2022016827A1 publication Critical patent/WO2022016827A1/zh
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/481—Astragalus (milkvetch)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/58—Reptiles
    • A61K35/583—Snakes; Lizards, e.g. chameleons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/07—Basidiomycota, e.g. Cryptococcus
    • A61K36/076—Poria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/21—Amaranthaceae (Amaranth family), e.g. pigweed, rockwort or globe amaranth
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/232—Angelica
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/284—Atractylodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/286—Carthamus (distaff thistle)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/64—Orobanchaceae (Broom-rape family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/72—Rhamnaceae (Buckthorn family), e.g. buckthorn, chewstick or umbrella-tree
    • A61K36/725—Ziziphus, e.g. jujube
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/80—Scrophulariaceae (Figwort family)
    • A61K36/804—Rehmannia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • A61K36/815—Lycium (desert-thorn)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/10—Preparation or pretreatment of starting material
    • A61K2236/13—Preparation or pretreatment of starting material involving cleaning, e.g. washing or peeling
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50—Methods involving additional extraction steps
    • A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • the invention belongs to the technical field of traditional Chinese medicine preparations, and in particular relates to a nerve regeneration compound preparation and a preparation method and application thereof.
  • Nerve damage can lead to partial or total loss of sensory and motor functions, with a high disability rate.
  • the clinical manifestations include muscle relaxation, muscle weakness, skin numbness, human weakness, numbness of limbs, and even paralysis.
  • Dialectical in traditional Chinese medicine is "atrophic disease”. , "Paralysis” and other categories. Due to modern traffic, industrial accidents, earthquake disasters, wars, and nerve trauma during tumor surgery, the incidence of nerve injury is increasing year by year, which seriously affects the quality of life of patients and brings heavy economic and social burdens to society and families. For more than 100 years, how to promote the repair and regeneration of damaged nerves has been a major problem and hotspot in the fields of pharmacy, neuroscience and medicine.
  • the purpose of the present invention is to: in view of the above problems, and provide a kind of nerve regeneration compound preparation and its preparation method and use, the compound preparation has obvious nerve growth promotion, promote the myelination of the regeneration nerve, promote the nerve of the denervated target muscle Reinnervation and protection after nerve injury provide a scientific basis for traditional Chinese medicine to promote nerve regeneration after injury, and provide a solid foundation for the clinical application of this prescription.
  • the present invention adopts the following technical scheme: a compound preparation for nerve regeneration, wherein, the ratio of parts by weight of each raw medicinal material in the compound preparation is: 10-20 parts of Astragalus membranaceus, 10-20 parts of Rehmannia glutinosa , 10-20 parts of Achyranthes, 6-15 parts of jujube, 6-15 parts of wolfberry, 6-15 parts of fried jujube seeds, 6-12 parts of Angelica, 3-9 parts of safflower, 6-15 parts of Poria, Stir-fried Atractylodes 6-15 servings and Wushao Snake 10-20 servings.
  • the ratio of parts by weight of each raw medicinal material in the compound preparation is: 10-20 parts of Astragalus membranaceus, 10-20 parts of Rehmannia glutinosa , 10-20 parts of Achyranthes, 6-15 parts of jujube, 6-15 parts of wolfberry, 6-15 parts of fried jujube seeds, 6-12 parts of Angelica, 3-9 parts of
  • the weight-to-number ratio of each raw medicinal material in the compound preparation is: 15 parts of raw astragalus, 15 parts of Rehmannia glutinosa, 15 parts of Achyranthes huai, 10 parts of jujube, 10 parts of wolfberry fruit, 10 parts of fried jujube kernels, 6 parts of Angelica, 3 parts of safflower, 10 parts of Poria, 10 parts of Fried Atractylodes and 15 parts of Wushao Snake.
  • the compound preparation also includes an effective dose of the compound preparation formula components and pharmaceutically acceptable excipients.
  • the dosage forms of the compound preparation for nerve regeneration include oral liquid, granules, granules and tablets.
  • the present invention also provides a preparation method of a nerve regeneration compound preparation, when the dosage form of the compound preparation is an oral liquid, its preparation method comprises the following steps:
  • the present invention also provides a compound preparation in the form of granules, the preparation method comprising the following steps:
  • the monarch medicine of described compound preparation raw Astragalus, Rehmannia glutinosa, Achyranthes fragrans, jujube, wolfberry fruit, fried Suan Zao Ren;
  • Subject medicine Angelica sinensis, safflower;
  • Adjuvant Poria, stir-fried Atractylodes;
  • Use medicine Black Snake.
  • the function of the compound preparation is: invigorating qi and blood, nourishing the five internal organs, promoting nerve growth, promoting myelin formation, dredging meridians and activating collaterals, suitable for nerve injury after qi deficiency and blood less, choroid disharmony, muscle weakness, skin numbness, Weak limbs.
  • the compound preparation for nerve regeneration provided by the present invention has the advantages of low toxicity and safety, and has the unique advantages of "coordination and overall comprehensive efficacy of multiple active ingredients, multi-level and multi-target points". On the basis of traditional empirical prescriptions, combined with the needs of modern nerve regeneration theory, it has formed characteristics in the composition of traditional Chinese medicine formulations.
  • the prescription uses astragalus to invigorate the middle and replenish qi, jujube to invigorate the qi and nourish the kidney, nourish the liver and soothe the nerves, rehmannia glutinosa nourishes the yin and nourishes the blood, nourishes the essence and fills the marrow, and the wolfberry nourishes the liver, improves eyesight, nourishes the kidney and moistens the nerves.
  • Lungs, Achyranthes, tonifying marrow and filling essence, and stir-fried Suanzaoren, etc. are used in combination to tonify qi, blood, yin and yang, and the deficiency of the five internal organs. The effect is reliable.
  • this recipe uses angelica and safflower. Poria cocos infiltrates dampness and invigorates the spleen and stomach, stir-frying Atractylodes to nourish the spleen and nourish the stomach, dry dampness and neutralize the middle, together with the effect of Wushao Snake to dispel wind and activate meridians, this formula is helpful for functional recovery after nerve injury.
  • the nerve regeneration compound preparation provided by the invention can obviously promote the growth of nerves, promote the myelination of the regenerated nerves, promote the reinnervation of the denervated target muscles and the protection after the nerve injury, which provides a scientific basis for the traditional Chinese medicine to promote the nerve regeneration after the injury. It provides a solid foundation for the clinical application of the prescription.
  • the present invention adopts the following technical scheme: a compound preparation for nerve regeneration, wherein the ratio of parts by weight of each raw medicinal material in the compound preparation is: 10-20 parts of Astragalus membranaceus, 10-20 parts of Rehmannia glutinosa, 10-20 parts of Achyranthes 20 servings, 6-15 servings of jujube, 6-15 servings of wolfberry fruit, 6-15 servings of fried sour jujube kernels, 6-12 servings of Angelica sinensis, 3-9 servings of safflower, 6-15 servings of Poria cocos, 6-15 servings of fried Atractylodes And black snake 10-20 servings.
  • the weight-to-number ratio of each raw medicinal material in the compound preparation is: 15 parts of raw astragalus, 15 parts of Rehmannia glutinosa, 15 parts of Achyranthes huai, 10 parts of jujube, 10 parts of wolfberry fruit, 10 parts of fried sour jujube kernel, 6 parts of Angelica, 3 parts of safflower, 10 parts of Poria, 10 parts of Fried Atractylodes and 15 parts of Wushao Snake.
  • the compound preparation further includes an effective dose of the compound preparation formula components and pharmaceutically acceptable excipients.
  • the dosage forms of the compound preparation for nerve regeneration include oral liquid, granules, granules and tablets.
  • the present invention also provides a preparation method of a compound preparation for nerve regeneration.
  • the dosage form of the compound preparation is an oral liquid
  • the preparation method includes the following steps:
  • the present invention also provides a compound preparation when the dosage form is granules, and its preparation method comprises the following steps:
  • the monarch medicine of the compound preparation raw Astragalus, Rehmannia glutinosa, Achyranthes huai, jujube, wolfberry fruit, fried Suan Zao Ren; minister medicine: Angelica sinensis, safflower; adjuvant: Poria, stir-fried Atractylodes; medicine: Black Snake.
  • the functions of the compound preparation are: invigorating qi and blood, nourishing the five internal organs, promoting nerve growth, promoting myelin formation, dredging meridians and activating collaterals, suitable for after nerve injury, qi deficiency and blood less, choroid disharmony, muscle weakness, skin numbness, Weak limbs.
  • Example 1 Nerve regeneration compound preparation is oral liquid
  • the preparation process of the oral liquid of the present invention is as follows: take 150 parts of raw astragalus, 150 parts of Rehmannia glutinosa, 150 parts of Achyranthes, 100 parts of jujube, 100 parts of wolfberry fruit, 100 parts of fried jujube kernel, 60 parts of Angelica sinensis and 30 parts of safflower , 100 parts of Poria, 100 parts of fried Atractylodes and 150 parts of Wushao snake;
  • Example 2 Nerve regeneration compound preparation as granules
  • the preparation process of the oral liquid of the present invention is as follows: take 150 parts of raw astragalus, 150 parts of Rehmannia glutinosa, 150 parts of Achyranthes, 100 parts of jujube, 100 parts of wolfberry fruit, 100 parts of fried jujube kernel, 60 parts of Angelica sinensis and 30 parts of safflower , 100 parts of Poria, 100 parts of Fried Atractylodes and 150 parts of Wushao Snake.
  • Example 3 Experimental study on the nerve regeneration compound preparation in promoting the regeneration of the sciatic nerve in rats
  • the rat sciatic nerve injury model was prepared by referring to the methods published by Smith GM et al.
  • the sciatic nerve function index (SFI) was measured, histological examination, and data statistical processing.
  • Example 4 Study on the protective effect of nerve regeneration compound preparation on ischemic brain injury in rats
  • mice 60 SD rats were randomly divided into 5 groups: low, medium and high groups of nerve regeneration compound oral liquid, Huatuo Zaizao pill group (positive control), ischemia group (negative control).
  • the traditional Chinese medicine low-dose, middle-dose and high-dose groups were given 0.9g/kg, 1.8g/kg, 3.6g/kg respectively;
  • Huatuo Zaizaowan group was given 1.44g/kg;
  • the ischemia control group was given equal volume of double distilled water.
  • Neurological function scoring standard (Modern Pharmacological Test Methodology (Volume 2)) (Note: scoring standard, the full score is 11 points, the higher the score, the more severe the animal behavior disorder); Serum SOD activity and MDA content determination, infarct volume determination, pathological tissue Observation, ultrastructural observation, and statistical processing of data.
  • the oral liquid of the compound preparation for nerve regeneration of the present invention can improve the recovery of nerve function in rats with cerebral ischemia, showing a dose-effect relationship; it can significantly improve the activity of SOD and the level of MDA, showing that it has a good protective effect on nerve damage.

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Abstract

一种神经再生复方制剂及其制备方法和用途，所述神经再生复方制剂中各原料药材的重量份数比为：生黄芪10-20份、熟地黄10-20份、怀牛膝10-20份、大枣6-15份、枸杞子6-15份、炒酸枣仁6-15份、当归6-12份、红花3-9份、茯苓6-15份、炒白术6-15份和乌梢蛇10-20份。所述复方制剂可用于制备治疗神经损伤疾病的药物，可制成口服液、颗粒剂、冲剂、片剂。

Description

一种神经再生复方制剂及其制备方法和用途 技术领域
本发明属于中药制剂技术领域，尤其涉及一种神经再生复方制剂及其制备方法和用途。
背景技术
神经损伤可导致感觉与运动功能的部分或全部丧失，致残率高，临床表现为，筋脉弛缓、肌无力、皮肤麻木、人体软弱、肢体麻木不仁、甚至瘫痪，中医学辩证属“痿症”、“痹症”等范畴。由于现代交通、工伤事故、地震灾害、战争、以及肿瘤手术中神经创伤等，神经损伤发生率逐年上升，严重影响患者生活质量，并给社会、家庭带来沉重的经济与社会负担。一百多年以来，如何促进受损的神经修复与再生一直是药学、神经科学与医学领域的重大难题和热点。
目前在临床上，针对神经损伤的药物稀少，中枢神经损伤采用神经生长因子治疗有一定疗效，但因神经生长因子(NGF)是从脑胶质瘤细胞培养液中提取的，因此，NGF临床试用存在着诱发肿瘤的潜在风险，周围神经损伤后，临床采用维生素B6，甲钴胺(弥可保)是维生素衍生物，具有一定的疗效。几十年来的临床实践告诉我们，“一病一药一靶点”的药物治疗模式，存在着极大的局限性，临床疗效欠佳。
为此，研发安全、有效的促神经再生中药，是广大患者的期盼，是社会重大需求，也是人类神经科学、药学与医学创新的需求。
如何解决上述技术问题为本发明面临的课题。
发明内容
本发明的目的在于：针对以上问题，而提供一种神经再生复方制剂及其制备方法和用途，该复方制剂具有明显的促神经生长，促再生神经的髓鞘形成，促失神经靶肌的神经再支配及神经损伤后的保护作用，为中药促损伤后的神经再生提供了科学依据，为该方剂临床应用提供了坚实的基础。
为了实现上述发明目的，本发明采用以下技术方案：一种神经再生复方制剂，其中，所述复方制剂中各原料药材的重量份数比为：生黄芪10-20份、熟地黄10-20份、怀牛膝10-20份、大枣6-15份、枸杞子6-15份、炒酸枣仁6-15份、当归6-12份、红花3-9份、茯苓6-15份、炒白术6-15份和乌梢蛇10-20份。
进一步地，所述复方制剂中各原料药材的重量份数比为：生黄芪15份、熟地黄15份、怀牛膝15份、大枣10份、枸杞子10份、炒酸枣仁10份、当归6份、红花3份、茯苓10份、炒白术10份和乌梢蛇15份。
进一步地，所述复方制剂还包括有效剂量的所述的复方制剂配方组分和药学上可接受的辅料。
进一步地，所述神经再生复方制剂的剂型包括口服液、颗粒剂、冲剂和片剂。
为了更好地实现上述发明目的，本发明还提供了一种神经再生复方制剂的制备方 法，所述复方制剂的剂型为口服液时，其制备方法包括以下步骤：
(1)按照所述重量份数的原料比例准备原料：生黄芪15份、大枣10份、熟地黄15份、枸杞子10份、怀牛膝15份、炒酸枣仁10份、当归6份、红花3份、茯苓10份、炒白术10份和乌梢蛇15份，水冲洗药材，去杂质；
(2)用去离子水浸泡，25℃，120分钟；
(3)水提，100℃，煎20分钟；
(4)取煎液，4℃，在无菌条件下静置12小时，滤过，浓缩，添加苯甲酸或苯甲酸钠；
(5)灌封，灭菌，即得所述口服液。
为了更好地实现上述发明目的，本发明还提供了一种复方制剂的剂型为颗粒剂时，其制备方法包括以下步骤：
(1)按照所述重量份数的原料比例准备原料：生黄芪15份、大枣10份、熟地黄15份、枸杞子10份、怀牛膝15份、炒酸枣仁10份、当归6份、红花3份、茯苓10份、炒白术10份、乌梢蛇15份；水冲洗药材，去杂质；
(2)用去离子水浸泡，25℃，120分钟；
(3)水提，100℃，煎20分钟；
(4)取煎液，4℃，在无菌条件下静置12小时，滤过，浓缩，添加苯甲酸或苯甲酸钠；
(5)干燥，制粒，封装，灭菌即得所述颗粒剂。
进一步地，所述的神经再生复方制剂在治疗神经损伤疾病的药物中的应用。
进一步地，所述复方制剂的君药：生黄芪、熟地黄、怀牛膝、大枣、枸杞子、炒酸枣仁；臣药：当归、红花；佐药：茯苓，炒白术；使药：乌梢蛇。
进一步地，所述复方制剂的功能是：益气补血，补益五脏，促神经生长，促髓鞘形成，通经活络，适用于神经损伤后气虚血少，脉络失和，肌无力，皮肤麻木，肢端软弱。
与现有的技术相比较，本发明的有益效果为：
(1)本发明提供的一种神经再生复方制剂具有低毒、安全的优势，更有“多种有效成份、多层面、多靶点的协调与整体综合功效”的独特优势，为此，我们在传统经验方剂基础上，结合现代神经再生理论需求，在中药药物配方组成方面形成特色。
(2)本方药物功效的创新点在于，针对神经损伤后主要病理机制，正气虚、气血虚、肝肾虚、五脏虚。中医理论“虚则补之”，用方采用黄芪补中益气，大枣益气养肾、补肝安神，熟地黄滋阴补血、益精填髓，枸杞子补肝明目、滋肾润肺，牛膝补髓填精，及炒酸枣仁等合用，补气补血补阴补阳，补五脏虚损，功效可靠。
(3)神经损伤肢体瘫痪，血不通，气血不畅，针对血瘀气阻，本方采用当归、红花。茯苓渗湿利水、益脾和胃，炒白术补脾养胃、燥湿和中，加之乌梢蛇祛风通经活络作用，本方剂有助于神经损伤后的功能恢复。
(4)本方剂药理学系列研究发现，本方剂具有明显的促神经生长，促再生神经的髓鞘形成，促失神经靶肌的神经再支配及神经损伤后的保护作用，为中药促损伤后的神经再生提供了科学依据，为该方剂临床应用提供了坚实的基础。
具体实施方式
发明提供的神经再生复方制剂具有明显的促神经生长，促再生神经的髓鞘形成， 促失神经靶肌的神经再支配及神经损伤后的保护作用，为中药促损伤后的神经再生提供了科学依据，为该方剂临床应用提供了坚实的基础。
本发明采用以下技术方案：一种神经再生复方制剂，其中，所述复方制剂中各原料药材的重量份数比为：生黄芪10-20份、熟地黄10-20份、怀牛膝10-20份、大枣6-15份、枸杞子6-15份、炒酸枣仁6-15份、当归6-12份、红花3-9份、茯苓6-15份、炒白术6-15份和乌梢蛇10-20份。
具体地，所述复方制剂中各原料药材的重量份数比为：生黄芪15份、熟地黄15份、怀牛膝15份、大枣10份、枸杞子10份、炒酸枣仁10份、当归6份、红花3份、茯苓10份、炒白术10份和乌梢蛇15份。
具体地，所述复方制剂还包括有效剂量的所述的复方制剂配方组分和药学上可接受的辅料。
具体地，所述神经再生复方制剂的剂型包括口服液、颗粒剂、冲剂和片剂。
为了更好地实现本发明的目的，本发明还提供了一种神经再生复方制剂的制备方法，所述复方制剂的剂型为口服液时，其制备方法包括以下步骤：
(1)按照所述重量份数的原料比例准备原料：生黄芪15份、大枣10份、熟地黄15份、枸杞子10份、怀牛膝15份、炒酸枣仁10份、当归6份、红花3份、茯苓10份、炒白术10份和乌梢蛇15份，水冲洗药材，去杂质；
(2)用去离子水浸泡，25℃，120分钟；
(3)水提，100℃，煎20分钟；
(4)取煎液，4℃，在无菌条件下静置12小时，滤过，浓缩，添加苯甲酸或苯甲酸钠；
(5)灌封，灭菌，即得所述口服液。
为了更好地实现本发明的目的，本发明还提供了一种复方制剂的剂型为颗粒剂时，其制备方法包括以下步骤：
(1)按照所述重量份数的原料比例准备原料：生黄芪15份、大枣10份、熟地黄15份、枸杞子10份、怀牛膝15份、炒酸枣仁10份、当归6份、红花3份、茯苓10份、炒白术10份、乌梢蛇15份；水冲洗药材，去杂质；
(2)用去离子水浸泡，25℃，120分钟；
(3)水提，100℃，煎20分钟；
(4)取煎液，4℃，在无菌条件下静置12小时，滤过，浓缩，添加苯甲酸或苯甲酸钠；
(5)干燥，制粒，封装，灭菌即得所述颗粒剂。
具体地，所述的神经再生复方制剂在治疗神经损伤疾病的药物中的应用。
具体地，所述复方制剂的君药：生黄芪、熟地黄、怀牛膝、大枣、枸杞子、炒酸枣仁；臣药：当归、红花；佐药：茯苓，炒白术；使药：乌梢蛇。
具体地，所述复方制剂的功能是：益气补血，补益五脏，促神经生长，促髓鞘形成，通经活络，适用于神经损伤后气虚血少，脉络失和，肌无力，皮肤麻木，肢端软弱。
实施例1：神经再生复方制剂为口服液
本发明口服液的制作过程为：取生黄芪150份、熟地黄150份、怀牛膝150份、大枣100份、枸杞子100份、炒酸枣仁100份、当归60份、红花30份、茯苓100份、炒白术100份和乌梢蛇150份；
其制备方法与步骤如下：
(1)水冲洗所述重量份数的药材，去杂质；
(2)配制成1190体积份，用去离子水浸泡，25℃，120分钟；
(3)水提，100℃，煎20分钟；
(4)取煎液，4℃，无菌条件下静置12小时，滤过，浓缩，添加甲苯酸或甲苯酸钠；
(5)灌封，灭菌，即得口服液制剂。
实施例2：神经再生复方制剂为颗粒剂
本发明口服液的制作过程为：取生黄芪150份、熟地黄150份、怀牛膝150份、大枣100份、枸杞子100份、炒酸枣仁100份、当归60份、红花30份、茯苓100份、炒白术100份和乌梢蛇150份。
其制备方法与步骤如下：
(1)水冲洗药材，去杂质；
(2)配制成1190体积份，用去离子水浸泡，25℃，120分钟；
(3)水提，100℃，煎20分钟；
(4)取煎液，4℃，无菌条件下静置12小时，滤过，浓缩，添加甲苯酸或甲苯酸钠；
(5)干燥，制粒，封装，灭菌即得颗粒剂。
实施例3：神经再生复方制剂促大鼠坐骨神经再生的实验研究
材料与方法：SD大鼠50只，随机分成5组，神经再生复方制剂口服液低、中、高剂量组，分别按生药0.9g/kg、1.8g/kg、3.6g/kg给药，弥可保组按625μg/kg给药，对照组给予等量体积的双蒸水。
借鉴Smith GM等发表的论文方法制备大鼠坐骨神经损伤模型，坐骨神经功能指数(SFI)测定，组织学检查，数据统计学处理。
结果：坐骨神经功能指数(SFI)，用中药组与弥可保组明显优于空白对照组，统计学分析P<0.05，差异呈显著性；组织学检查，用本发明的神经再生复方制剂的中药组可见再生神经纤维较密，髓鞘较厚，明显优于空白对照组，统计学分析P<0.05，差异呈显著性。
结果表明：本发明的神经再生复方制剂可促损伤后的大鼠坐骨神经再生，髓鞘形成与功能恢复。
实施例4：神经再生复方制剂对大鼠缺血性脑损伤的保护作用研究
材料与方法：SD大鼠60只，随机分为5组，神经再生复方制剂口服液低、中、高组，华佗再造丸组(阳性对照)，缺血组(阴性对照)。中药低、中、高剂量组分别按0.9g/kg、1.8g/kg、3.6g/kg给药；华佗再造丸组1.44g/kg给药；缺血对照组给予等体积双蒸水。神经功能评分标准(现代药理试验方法学(下册))(注：评分标准，满分11分，分数越高，动物行为障碍越严重)；血清SOD活性和MDA含量测定，梗死体积测定，病理组织观察，超微结构观察，数据统计学处理。
结果：(1)中药高剂量组和华佗再造丸组，24h、48h、72h的大鼠神经功能评分显著下降(P<0.05与0.01)。
(2)中药中剂量、高剂量组与华佗再造丸组与缺血组相比较，梗死体积显著降低(P<0.05与0.01)。
(3)中药中剂量、高剂量组及华佗再造丸组与缺血组相比较，SOD活性显著增加， MDA含量显著降低(P<0.05与0.01)。
结果表明：本发明的神经再生复方制剂口服液可改善大鼠脑缺血的神经功能恢复，呈剂量——效应关系；并可明显提高SOD活力和MDA水平显示，具有良好的神经损伤保护作用。
以上所述仅为本发明的较佳实施例，并不用以限制本发明，任何在此基础上，对其中配方和工艺的局部变动，都应在本发明的保护范围之内。

Claims (7)

  1. 一种神经再生复方制剂，其特征在于，所述复方制剂中各原料药材的重量份数比为：生黄芪10-20份、熟地黄10-20份、怀牛膝10-20份、大枣6-15份、枸杞子6-15份、炒酸枣仁6-15份、当归6-12份、红花3-9份、茯苓6-15份、炒白术6-15份和乌梢蛇10-20份。
  2. 根据权利要求1所述的神经再生复方制剂，其特征在于，所述复方制剂中各原料药材的重量份数比为：生黄芪15份、熟地黄15份、怀牛膝15份、大枣10份、枸杞子10份、炒酸枣仁10份、当归6份、红花3份、茯苓10份、炒白术10份和乌梢蛇15份。
  3. 根据权利要求1或2所述的神经再生复方制剂，其特征在于，所述复方制剂还包括有效剂量的所述的复方制剂配方组分和药学上可接受的辅料。
  4. 根据权利要求1-3任一项所述的神经再生复方制剂，其特征在于，所述神经再生复方制剂的剂型包括口服液、颗粒剂、冲剂和片剂。
  5. 根据权利要求1-4任一项所述的神经再生复方制剂的制备方法，其特征在于，所述复方制剂的剂型为口服液时，其制备方法包括以下步骤：
    (1)按照所述重量份数的原料比例准备原料：生黄芪15份、大枣10份、熟地黄15份、枸杞子10份、怀牛膝15份、炒酸枣仁10份、当归6份、红花3份、茯苓10份、炒白术10份和乌梢蛇15份，水冲洗药材，去杂质；
    (2)用去离子水浸泡，25℃，120分钟；
    (3)水提，100℃，煎20分钟；
    (4)取煎液，4℃，在无菌条件下静置12小时，滤过，浓缩，添加苯甲酸或苯甲酸钠；
    (5)灌封，灭菌，即得所述口服液。
  6. 根据权利要求1-4任一项所述的神经再生复方制剂的制备方法，其特征在于，所述复方制剂的剂型为颗粒剂时，其制备方法包括以下步骤：
    (1)按照所述重量份数的原料比例准备原料：生黄芪15份、大枣10份、熟地黄15份、枸杞子10份、怀牛膝15份、炒酸枣仁10份、当归6份、红花3份、茯苓10份、炒白术10份、乌梢蛇15份；水冲洗药材，去杂质；
    (2)用去离子水浸泡，25℃，120分钟；
    (3)水提，100℃，煎20分钟；
    (4)取煎液，4℃，在无菌条件下静置12小时，滤过，浓缩，添加苯甲酸或苯甲酸钠；
    (5)干燥，制粒，封装，灭菌即得所述颗粒剂。
  7. 根据权利要求1-4任一项所述的神经再生复方制剂在治疗神经损伤疾病的药物中的应用。
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