GB2581592A

GB2581592A - Preparation procedure for panax notoginseng medicinal liquor for oral administration for treating rheumatic ostalgia

Info

Publication number: GB2581592A
Application number: GB2004346.9A
Authority: GB
Inventors: Hu Jiangning; Chen Peng; Kong Qiongrong; Wu Jian; Wu Hualing; Feng Yifan; Xu Hongming; Wang Ruwei
Original assignee: Yunnan Conba Xitao Pharmaceutical Co Ltd
Current assignee: Yunnan Conba Xitao Pharmaceutical Co Ltd
Priority date: 2017-10-20
Filing date: 2017-12-22
Publication date: 2020-08-26
Anticipated expiration: 2037-12-22
Also published as: WO2019077400A1; CN109692302B; GB202004346D0; GB2581592B; CN109692302A

Abstract

A preparation process for a Panax notoginseng medicinal liquor for oral administration for treating rheumatic ostalgia, which mostly consists of steps of enzymolysis, gel column filtration, soaking, diacolation and clarification.

Description

PREPARATION PROCEDURE OF ORALLY TAKEN PANAX NOTOGINSENG MEDICINAL LIQUOR FOR TREATING RHEUMATIC OSTALGIA

FIELD OF THE INVENTION

The present invcntion relates to the field of traditional Chinese medicine technology, particularly relates to a preparation procedure of orally taken PCIMIX Nologinseng medicinal liquor for treating rheumatic ostalgia.

BACKGROUND OF THE INVENTION

The common rheumatic osteopathy include osteoarthritis, rheumatic arthritis, rheumatoid arthritis, periarthritis, cervical spondylosis, lumbar spondylopathy, gout, anlwlosing spondylitis, femoral head necrosis, sports injury (the old and new traumatic injury), varices, nameless swelling and pain, hemiplegia, synovitis, tenosvnovitis, pleurisy, tennis elbow and so on. According to survey reports from the World Health Organization (WHO) in recent years, more than 2.5 billion people (about 40% of the world's population) arc suffering from different degrees of rheumatic osteopathy, of which 1.08% are suffering from paralysis that caused by rheumatoid or gout. Preliminary epidemiological investigation suggested that the total incidence of osteoarthritis in China is about 15%, the incidence in population under age 40 is 2 -3%, the incidence in population aged 40 to 60 is 25 -30%, the incidence in population over 60 is up to 65% (higher incidence in western countries). For this disease alone, there are more than 200 million patients with varying degrees in middle-aged and elder mainly. Current therapies for rheumatic osteopathy include dialectical therapy of traditional Chinese medicine, analgesic chemical treatment (celebrcx, loxonin, etc.), physiotherapy, acupuncture and massage, block therapy, etc. However, the majority of chemical medicines such as celebrex arc used to relieve pain, cure the symptoms but not the root cause. And they also have long-term side effects of medication. In addition, surgery and other treatment have high risk, high cost, and high risk of recurrence. The rheumatism belongs to "arthralgia-syndromc" in traditional Chinese medicine, which is caused by physical weakness with pathogenic wind-cold, dampness pathogen, and poor blood flow. Traditional Chinese medicine has mild and long-lasting effects, less toxic and side effects, and good tolerance in long-term treatment. The Chinese medicine compounds can play an integrated regulatory role in multiple pathological stages of rheumatism through multi-approach, multi-link, and multi-target. The Chinese medicine compounds can also improve symptoms of patients, enhance physical fitness, delay the development of the disease, prevent and improve bone destruction. Chinese ancient books record a large number of traditional Chinese medicines for rheumatic ostalgia. For example, Shanghan Lun (Treatise on Cold Pathogenic Diseases) records "The wind pathogen and dampness pathogen can congregate to make joints painful, the joints are too painful to flex or stretch. With the developing of the disease, patient will feel jonits arc more painful than before, sweating, shortness of breath, and unfavorable in urination. Gancao Fuzi Tang can be used to treat these symptoms above". Jingui Yaolue (Synopsis of Golden Chamber) records "Guizhi Shaoyao Zhimu Tang can be used to treat pain in limb and joint, body weak, swollen feet such as prolapse, dizziness, shortness of breath, feeling like vomiting". At present, the sales of rheumatic osteopathy medicines such as Hongmao Yaojiu, Hulisan, Panlongqi, and Panax Notoginseng medicinal liquor have reached hundreds of millions yuan in the market.

As an ethnodmg of Yunnan province, Panax Notoginseng medicinal liquor has several medicinal functions such as relieving rigidity of muscles and activating collaterals, stasis-dissipating and pain-easing, expelling wind-evil and removing wetness, strengthening tendons and boncs. It is used to treat traumatic injury, rheumatic bone pain and numbness of limbs. Its quality standards are included in the standards issued by the Ministry of Health, which records medical prescription with 21 kinds of Chinese medicinal materials including Nologinseng Radix el Rhizome, Curcumae Rhizoma, Scorpio, Eapolyphaga Sea Steleophaga, Psoraleae Fructus, Epimedii Folium, Henry chloranthus herb, Herba Ainslicteae, Angelicae sinensis Radix, Achyranthis Bidenialae Radix, Acanihopanacis Cortex, Aconili Radix coda, Sappan Lignum, Sargentodoxae can/is, Chuanxiong Rhizoma, Draconis San guts. Carthami.flos, Ohbanum (processing with vinegar), Myrrha (processing with vinegar), Rhizome Corydalis (processing with vinegar), Operi Rhizoma (processing with vinegar). The quality standards also record the preparation method of the medicinal liquor as follows: crushing Noioginseng Radix el Rhizome, Scorpio, Eupolyphaga Sea Steleophaga, Draconis San guts into coarse powders, crushing the other medicinal materials into coarsest powders, mixing the coarse powders and the coarsest powders. According to percolation method under liquid extracts and extracts (General Rule 0189), using more than 50% Chinese white liquor as solvent, soaking for 15 days in a closed atmosphere, infiltrating slowly, collecting 8400 mL of infiltrating solution, resting, filtering, then getting the product. For one thing, the Panax notoginseng medicinal liquor contains poisonous medicinal materials such as Scorpio, Enpolyphaga Sen Sieleophaga, Rhizoma el Radix Chloranthi, Herba Aincliaeae, and Aconiti Radix cocta, and its quality standard only identifies the Panax notoginseng medicinal liquor and does not control the efficacy indicators. These medicinal materials usually work through a certain amount of toxic ingredients to relieve rigidity of muscles mid activate collaterals, relieve stasis and relieve pain, expel wind-evil and remove wetness, and strengthen muscles mid bones, just as colchicine's effect on treating rheumatoid arthritis. Furthermore, low dosage of medicinal content may lead to clinical ineffectiveness, and high dosage may lead to liver injury, renal injury, heart injury and nervous system injury. Thus, controlling medicinal content strict is an important measure to ensure the safety and effectiveness of medicine. Such simple production process and quality control standards may hide some dangers for clinical applications. For another, there may be many problems such as precipitation and poor taste during medicinal liquor production and sales process. Therefore, the research on the traditional Chinese medicines production technology of complex prescription such as Panax notoginseng medicinal liquor is the current research hotspot and also an urgent problem to be solved.

Actually, several related process researches have been reported, but most of these studies reported extraction in simple recipe, or compound recipe with simple soaking and percolation extraction. Most of diem only consider the extraction of active ingredients such as Ponca notoginseng, and do not involve the content control of various toxic medicinal materials. For example, percolation extraction process of Panax notoginseng has been reported, which has investigated different effects in methods conditions (such as ethanol concentration, solvent fold amount and infiltration rate in percolation) during Panax notoginseng extraction preparation (Tan Chaoyang, el al. Study on percolation extraction process of Panax notoginseng [J], Chinese Journal of Information on Traditional Chinese Medicine, 2010, 17(4): 51 -52). The optimum condition for the extraction with total notoginseng saponin and total amino acids 7.801% and 1.771% respectively, was adding 12-fold volume of 50% ethanol and percolating at a rate of 1 -3 mL/(mitrkg). However this extraction method has some disadvantages. Firstly, this method has low leaching concentration of medicinal materials by adding 12-fold volume of 50% ethanol, which means surplus ethanol should be recovered. Secondly, this method's low infiltration percolation velocity decreases production efficiency, which means industrial production should be restricted. Thirdly, this method just investigates Panax notoginseng without mention of extraction or content control of others medicinal materials in compound preparation. Besides, patent CN10462607A "Traditional Chinese medicine composition for treating rheumatic and rheumatoid diseases" discloses a traditional Chinese medicine composition which comprises parts by weight of 50 -90 parts of Nologirmeng Radix el Rhizome, 30 -60 parts of Olibanum, 30 -60 parts of Alyrrhet, I() -20 parts of Strychni semen, 20 -30 parts of stir-baked Squama marlins, 20 -60 parts of Angelicae sinensis Radix, 20 -60 parts of Chuanx-iong Rhizotna, 20 -60 parts of Aconiti Radix, 20 -60 parts of Aconite Kusnezeii Radix, 30 -90 parts of Eupotyphaga Seu Steleophaga, 20 -90 parts of Radix Angelicae Dahuricae, 30 -90 parts of Carthami.fins, 15 -30 parts of Akebiae Can/is. 30 -50 parts of Centipede, 10 -15 parts of Scorpio, 30 -90 parts of Radix Dtpsaci from Sichuan of China, 10 -15 parts of Zaocys, 30 -60 parts of Pheretima, 30 -60 parts of Cc-tulis Sinomenii, 30 -60 parts of Piperis Kadsurae Cauhs, 30 -60 parts of Trachelospermi Cauhs et To//um, 60 -90 parts of Zingiberis Rhizoma. The composition was extracted by following steps: adding 4000 m L anhydrous ethanol, soaking hermetically at room temperature for 7 days, filtrating and collecting filtrate to yield Panax notoginseng medicinal liquor. The patent also discloses the composition's clinical administration method is to dip and apply the medicine composition gauze. From the foregoing, the patent employs conventional preparation process and focuses on the composition of the traditional Chinese medicine. It does not analyze the factors affecting the extraction of toxic medicinal materials such as Aconiti Radix, Eupolyphaga Seu Steleophaga and Scorpion, and sovereign herb Notoginseng Radix et Rhizome. There may be problems such as unstable active ingredients and toxic ingredients in medicine composition, which is not suitable for oral administration.

BRIEF SUMMARY OF THE INVENTION

The subject invention provides a preparation procedure of orally taken Parma Nologinseng medicinal liquor for treating rheumatic ostalgia, which is mainly composed of enmmolysis, gel column filtration, soaking, percolation and clarification The preparation procedure is eeo-friendly, economical, and is used in producing clinically safe, effective and quality controlled medicinal liquor.

Panax Nologinseng medicinal liquor prescription comprises parts by weight of 50 parts of Notoginseng Radix et Rhizome, 40 parts of Curcumae Rhizome, 10 parts of Scorpio, 30 parts of Eupolyphaga Seu Sieleophaga, 50 parts of Psoraleae Free/us, 50 parts of Epimedii F0117117 7, 60 parts of Henry ehloranthus herb, 80 parts of Herba Ainsliaeae, 60 parts of Angelicae sinensis Radix, 50 parts of Achyranthis Bidentatae Radix, 60 parts of Accmthopanacis Cortex, 20 parts of Aconiti Radix coda, 40 parts of Sappall Lignum, 60 parts of Sargentodoxae cauhs, 30 parts of Chuanxiong Rhizoma, 10 parts of Draconis Sanguis, 20 parts of Carthami fibs, 30 parts of Ohbanum (processing with vinegar), 30 parts of Myrrh(' (processing with vinegar), 40 parts of Rhizome Corydahs (processing with vinegar), 40 parts of Cyperi Rhizoma (processing with vinegar) . Further, Notoginseng Radix et Rhizome is sovereign drug iii this medicinal liquor. It has effect of promoting blood circulation for removing blood stasis, swelling and pain. It is suitable for treating blood stasis syndromes in traumatism. It acts on liver, stanch bleeding and disperse blood stasis without affecting other body fimctions.

Minister drug from this medicinal liquor can promote qi and invigorate the circulation of blood, regulate menstruation and stop pain. For example, Curcumae Rhizoma is acrid and intense in flavor, specializes in qi and blood, mainly used for removing stasis and accumulation lump. Eupolyphaga See Steleophaga invigorates blood circulation to remove blood stasis, induces menstruation to stop pain. Angel/cue sinensis Radix is sweet and warm, has efficacy of replenishing blood and regulating menstruation. And it is also acrid and warm, has efficacy of invigorating the circulation of blood and relieving pain..cichttan lovage rhizome is acrid and warm, invigorates blood circulation to remove stasis, promotes the circulation of qi and stops pain. Combining Angelicae sinensis Radix and Sichuan lovage rhizome can improve therapeutic effect. Sappan Lignum is acrid and salty, invigorates blood circulation to remove stasis, diminishes swelling and stops pain. Draconis Sanguis can act on blood, remove blood stasis to stop pain, is an important medicine in traumatology and other stasis pain syndromes. Combining Myrrha and Ohbanum can improve therapeutic effect in traumatic injury and stasis pain. Cyperi Rhizoma is acrid and bitter, soothes liver and resolves depression, regulates menstruation and relieves pain, is a significant medicine for regulating menstruation in gynaecology. Rhizome Coudalis is warm and acrid, is suitable for invigorating blood circulation, promoting the circulation of qi and relieving pain. It is said that Rhizome Corydalis can promote the qi stagnation in blood and the blood stasis in qi, treat various pain syndromes throughout the body specially. A combination of minister drugs can promote the qi, remove stasis and relieve pain.

There are several minister drugs that can expel wind-evil and remove wetness, relax tendons and activate collateral For example, Scorpio is wandering, acts in liver mainly, calms hepatic wind, removes obstruction in collateral, and relieves spasm by calming endogenous wind. It is an important medicine for convulsion. Aconite Radir cocta is acrid, hot, ascending, dispersive, bitter and thy. It is said that the medicine can dredge quickly, open joint and skin, and expel cold and wet. It has efficacy of dispelling wind-dampness, warming meridians to eliminate cold, and obvious analgesic effect. It is used for wind chills and arthromyodynia. Acanthopanacis Cortex is acrid, bitter and warm, good at dispelling wind, drying dampness, dispelling cold, tonifying the liver and kidney, and is mostly used by the elderly and weakness those who have been sick for a long time. A combination of those minister drugs that works to dispel wind-dampness, relax tendons and activate collateral.

There are several minister drugs that can tonify kidney and strengthen yang, strengthen tendons and bones. For example, l'soraleae Fruchis warms kidney, generates yang from yin, is used for strengthening huo and tonifying tu. Epimedii Voltam is acrid and warm, dispels cold, is mostly used for tonifying kidney and strengthening yang, acts on liver and kidney, strengthens tendons and bones, and dispels wind-dampness. A combination of those minister drugs can tonify kidney and strengthen yang Adjunctive drugs: Saigentodoxtre can/is invigorates the circulation of blood and menstruation, dispels wind-dampness. Henry chloranihus herb dispels wind-dampness, invigorates blood circulation to remove blood stasis. Herba Ainshaeae promotes the qi, invigorates blood, reunites fractured tendons and bones, dispels wet and stops pain.

Envoy drugs: Achyranthis Bidentatae Radix is good at inducing qi and blood to descend, is mostly used for chmmel affinity to induce down. It also can invigorate blood circulation to remove stasis efficiently, tonify the liver and kidney, strengthen the tendons and bones, dispel wind-dampness. Chinese white liquor is only solvent, which works with Achyranthis Bidentatae Radix on ascending, descending, exiting and entering the qi and blood.

The medicinal liquor, including 21 kinds of traditional Chinese medicine, is acrid and warm, moderates the relationship between promoting and reliving, moistening and dryness, ascending and descending, reinforcement and elimination. It removes stasis to stop pain without damaging blood, expels wind mid removes cold without damaging yin, relaxes tendons and activates collateral without damaging healthy energy, strengthens tendons and bones without collecting exogenous pathogen. Those Chinese medicines work together to improve efficiency, and perform their duties respectively The preparation of Panax Notoginseng medicinal liquor in the present invention employs the following methods: (1) crushing the Scorpio and the kupollphaga Seu Steleophaga into coarse powders, adding 0.8 -2 volumes of 30% -50% Chinese white liquor to extract the coarse powders, adding 0.08% -0.12% weight of the coarse powders bromclain at 50 -60°C, infiltrating and dissolving for 3 -5 hours, performing purification in Superdex peptide column, eluting with 1 -2 volumes of 30% -50% Chinese white liquor and discarding the eluent, then eluting with 2 -4 vohunes of 30% -50% Chinese white liquor and collecting the eluting solvent to reserve; (2) crushing the Aconite Radix cocta, Henry chloranthus herb, Herber Ainshaeae, Cyperi rhizoina, Chuanxiong Rhizoina into coarse powders, adding those coarse powders into percolation apparatus, adding reserving eluting solvent prepared in step (1) and 1 -2 volumes of 50% -60% Chinese white liquor, soaking hermetically at room temperature for 12 -36 hours, then crushing the remaining medicinal materials into coarse powders, adding those coarse powders into the above percolation apparatus, adding 3 -7 volumes of 50% -60% Chinese white liquor, soaking hermetically for 10 -20 days with light-proof packing materials; (3) adjusting flow rate of percolation to 3 -5 mL/(min*kg), adding 50% -60% Chinese white liquor constantly, collecting 8400 mL percolate for each prescription, resting the percolate, then filtrating through filter plate with particle size of 74 um to yield Panax nologinseng medicinal liquor.

Further, the extraction solvent in step (1) is 1.5 volumes of 40% Chinese white liquor, and the eluting solvent in step (1) is 3 volumes of 40% Chinese white liquor. The amount of bromelain added in step (1) is 0.10% weight of the coarse powders.

The present invention provides a preparation procedure of Panax Notoginseng medicinal liquor for oral administration for treating rheumatic ostalgia. The medicinal liquor is bright red-brown in color, can be stored at room temperature for a long time without precipitation, and treats rheumatic ostalgia significantly. The specifically beneficial effects of the medicinal liquor are as follows: (1) Scorpio and Eupolyphaga Seu Stethophaga are two kinds of toxic animal medicinal materials, which are rarely reported for rheumatism currently. The present invention uses 1.5 volumes of Chinese white liquor to soak Scorpio and Eupolyphaga S'eu Steleophaga, then uses fibrinolytic enzyme from Eupolyphaga Seu Steleophaga and 0.10% bromelain io decompose long-chain scorpion venom proteins (such as BmK-11IM, BmP09, NIX, CTX iii Scorpio) to reduce some effects such as muscle depression of these ingredients on the body. Besides, the present invention employs 1.5 volumes of Chinese white liquor to soak medicinal materials in preparation, which reduces the amount of soaking solvent significantly. It facilitates subsequent infiltration to yield liquor, reduces solvent recovery process and production costs.

(2) The present invention performs bromelain enzymatic hydrolyzate purification in Superdex peptide column to remove impurity and macromolecule such as undecomposed long-chain scorpion venom protein, then elutes with 3 volumes of 40% Chinese white liquor to enrich composition whose molecular weight below 6.5 KDa effectively, adds Aconni Radix coda, Henry chthranthus herb, Herber Ainshaeae, Open rhizoma, Chuanxiong Rhizoma into eluting solvent from step(1) and soaks hermetically. During long-term experimental research, it is found that soaking process of those five Chinese medicinal materials can reduce toxicity of Aconiti Radix coda, Henry chloranthas herb, Herba Ainsliaeae. In particular, the content of aconitine in Chuanxiong Rhizoma can be significantly reduced through the attenuating effect of compatibility. The experiment results suggest that aconitine is not detected in the Punta notoginseng medicinal liquor which is prepared by the above process. The long-term toxicity experiments in rats suggest that there is no adverse reaction of the Pan ax nologinseng medicinal liquor, which is prepared by this process, at a high dose of 1.0 g/kg/day in rats. And rats have no toxic side effect after continuous intragastric administration for 6 months.

(3) The main medicinal ingredients such as notoginsenoside, icariin, psoralen and isopsoralen in the Pan ax notoginseng medicinal liquor, which is prepared by the preparation process from the present invention, have stable content, controllable quality, 90% -98% transfer rate. Animal experiments show that the Panax notoginseng medicinal liquor can effectively inhibit delayed t)Te hypersensitivity (DTH) reaction in mice which are induced by dimethyl chlorobenzene (DNCB), and effectively.-reduce button granuloma and toe swelling in rats.

The prevent invention provides a safe, effective mid quality controllable preparation process for a Panax notoginseng medicinal liquor. Chinese white liquor with different concentrations is used as the only solvent in the whole preparation process, and it doesn't need to recover because of its low dosage, which makes the process economical and environment-friendly. The medicinal liquor has clear main medicinal ingredients, stable contents, 110 obvious side effects It is safe and suitable for long-tenn use.

EXAMPLES

The following further describes the present invention with reference to following examples. The examples below further illustrate the invention, rather than limiting the scope thereof

EXAMPLE1

The preparation processing method included the following steps in sequence: (1) crushing the Scorpio 10 g and the kupolyphaga Seu Stekophaga 30 g into coarse powders, adding 1.5 volumes of 40% Chinese white liquor to extract the coarse powders, adding 0.10% weight of the coarse powders bromelain at 55 "C, infiltrating and dissolving for 4 hours, performing purification in Superdex peptide column, eluting with 1.5 volumes of 40% Chinese white liquor and discarding the eluent, then eluting with 3.0 volumes of 40% Chinese white liquor and collecting the eluting solvent to reserve; (2) cnishing the Aconiti Radix coda 20 g, Henry chloranthus herb 60 g, Herba Ainsliaeae 80 g, Cyperi rhizome, 40 g, Chuanxiong Rhizome, 30 g into coarse powders, adding those coarse powders into percolation apparatus, adding reserving eluting solvent prepared in step (1) and 1.5 volumes of 55% Chinese white liquor, soaking hermetically at room temperature for 24 hours, then crushing the Radix et Rhizome 50 g, Curcumae Rhizome, 40 g, Psorathae kructus 50 g, Epimedii Fohum 50 g, Angehcae sinensis Radix 60 g, Sappan Lignum 40 g, SargeModoxae can/is 60 g, Draconis Sanguis 10 g, Carthami.flos 20 g, Olibanum (processing with vinegar) 30 g, Myrrha (processing with vinegar) 30 g, Rhizome Corydahs (processing with vinegar) 40 g, Achyranthis Bickntatae Radix 50 g, Acanthopanacis Cortex 60 g into coarse powders, adding those coarse powders into the above percolation apparatus, adding 5.0 volumes of 55% Chinese white liquor, soaking hermetically for 15 days with light-proof packing materials; (3) adjusting flow rate of percolation to 3 -5 mUonin.kg), adding 55% Chinese white liquor constantly, collecting 8400 inL percolate for each prescription, resting the percolate (0 -4 °C), and filtrating through filter plate with particle size of 74 vim to yield Panax notoginseng medicinal liquor.

EXAMPLE2

The preparation processing method included the following steps in sequence: (1) crushing the Scorpio 10 g and the Eupolyphaga Sea Stekophaga 30 g into coarse powders, adding 0.8 volumes of 30% Chinese white liquor to extract the coarse powders, adding 0.08% weight of the coarse powder bromelain at 50 C. infiltrating and dissolving for 5 hours, performing purification in Superdex peptide column, eluting with 2.0 volumes of 30% Chinese white liquor and discarding the eluent, then eluting with 4.0 volumes of 300/ Chinese white liquor and collecting the eluting solvent to reserve; (2) crushing the Aconite Radix coda 20 g, Henry chloranthus herb 60 g, Herba A inshaeae 80 g, Operi rhizoma 40 g, Chuanxiong Rhizoma 30 g into coarse powders, adding those coarse powders into percolation apparatus, adding reserving eluting solvent prepared in step (1) and 1.0 volume of 60% Chinese white liquor, soaking hermetically at room temperature for 12 hours, then crushing the Radix et Rhizome 50 g, Curcumae Rhizoma 40 g. Psorakae Fructus 50 g. Epimedii Folium 50 g. Angel/cue sinensis Radix 60 g. Sappan Lignum 40 g. Sargentodoxae caulis 60 g, Draconis Sanguis 10 g, Carthami flos 20 g, Olibamun (processing with vinegar) 30 g, Myrrha (processing with vinegar) 30 g, Rhizome Cotydalis (processing with vinegar) 40 g, Achyranthis Bidentatae Radix 50 g, Acanthopanacis Cortex 60 g into coarse powders, adding those coarse powders into the above percolation apparatus, adding 7.0 volumes of 50% Chinese white liquor, soaking hermetically for 20 days with light-proof packing materials; (3) adjusting flow rate of percolation to 3-5 mL/(min-kg), adding 60% Chinese white liquor constantly, collecting 8400 mL percolate for each prescription, resting the percolate (0 -4 °C), then filtrating through filter plate with particle size of 74 [an to yield P ((MIX nologinseng medicinal liquor.

EXAMPLE 3 10

The preparation processing method included the following steps in sequence: (1) crushing the Scorpio 10 g and the Enpotyphaga Sen Steleophaga 30 g into coarse powders, adding 1.5 volumes of 50% Chinese white liquor to extract the coarse powders, adding 0.12% weight of the coarse powders bromelain at 6012, infiltrating and dissolving for 3 hours, performing purification in Superdex peptide column, eluting with 1.0 volume of 50% Chinese white liquor and discarding the cluent, then eluting with 2.0 volumes of 50% Chinese white liquor mid collecting the eluting solvent to reserve; (2) crushing the Aconite Radix cocta 20 g, Henry chloranthus herb 60 g, Herba A thshaeae 80 g, (yperi rhizoma 40 g, Chuanxiong Rhizoma 30 g into coarse powders, adding those coarse powders into percolation apparatus, adding reserving eluting solvent prepared in step(1) and 2.0 volumes of 50% Chinese white liquor" soaking hermetically at room temperature for 36 hours, then crushing the Radix et Rhizome 50 g, Curcumae Rhizoma 40 g, Psoraleae Fructus 50 g, Epimedii Fohum 50 g, Angehcae sinensis Radix 60 g, &ippon Lignum 40 g, SargeModoxae can/is 60 g, DracoMs Sanguis 10 g, Carthami.flos 20 g, Olibanum (processing with vinegar) 30 g, Myrrha (processing with vinegar) 30 g, Rhizome Corydahs (processing with vinegar) 40 g, Achyranthis Bidentatae Radix 50 g, Acanthopanacis Cortex 60 g into coarse powders, adding those coarse powders into the above percolation apparatus, adding 3.0 volumes of 50% Chinese white liquor, soaking hermetically for 10 days with light-proof packing materials; (3) adjusting flow rate of percolation to 3-5 mu(minlg), adding 60% Chinese white liquor constantly, collecting 8400 itiL percolate for each prescription, resting the percolate (0 -4 °C), then filtrating through filter plate with particle size of 74 pm to yield Panax notoginseng medicinal liquor.

EXAMPLE 4: CONTENT DETECTION METHODS (1) Content Detection Method of Notoginsenoside Ginsenoside Rgl was determined by EIPLC (Chinese pharmacopoeia version 2015 general rule 0512).

Chromatographic conditions and system suitability tests with chromatographic condition -was C18 column, mobile phase A was acetonitrile and mobile phase B was water, gradient elution followed the table below with flow rate of 1 5 mL/min, at detection wavelength of 203 nm and temperature at 25 "C. The number of theoretical plates calculated from the gmsenoside Rgl peak should be no less than 6000.

Time (minutes) ) Mobile phase A (%) Mobile phase B (%) 0 20 80 20 80 46 54 ss 55 45 55 45 61 90 10 90 10 Preparation of reference solution: the proper ginsenoside Rgl was weighted accurately, added 50% ethanol to make a solution containing ginsertoside Rgl 0.3 mg/mL Preparation of test sample solution: the medicinal liquor was measured 10 mL precisely, added to 0900 macroporous anion decolorizing resin chromatographic column ( d= 1.2-1.5 cm, V = 20 cm3), eluted by 60 mL 50% ethanol and collected the eluent, concentrated under reduced pressure to dry, added 15 m L water, extracted with methylene chloride twice times by shaking 15 mL once a time, abandoned the methylene chloride liquid. The water solution was concentrated under reduced pressure to dry, added 50% ethanol solution and moved into 10 mL volumetric flask, added 50% ethanol to scale, shaken well, filtered and collected the filtrate.

The measurement method: reference solution and test sample solution were precisely sucked lthiL respectively, injected into the liquid chromatograph, then determined.

The content of Radix et Rhizome which was calculated by ginsenoside Rgl (C42H72014) was 0.20 mg/mL in Pan ax Notoginseng medicinal liquor prepared in example 1, (2) Content Detection Method of icariin leariin was determined by H PLC (Chinese pharmacopoeia version 2015 general rule 0512).

Chromatographic conditions and system suitability tests with chromatographic condition was C18 column, mobile phase A was aeetonitrile and mobile phase B was water, gradient elution followed the table below with flow rate of 1.0 mL/min, at detection wavelength of 270 nm and temperature at 25 t. The number of theoretical plates calculated from the icariin peak should be no less than 1500.

Time (minutes) Mobile phase A (%) Mobile phase B (% ) 0 30 70 30 70 90 10 90 10 Preparation of reference solution: the proper icariin was weighted accurately, added 50% ethanol to make a solution containing icariin 0.1 mg/ mL.

Preparation of test sample solution: the medicinal liquor was measured 10 mL precisely, added into D900 macroporous anion decolorizing resin chromatographic column ( d= 1.2-1.5 cm, V = 20 ere), eluted with 60 mL 50% ethanol and collected the eluent, concentrated under reduced pressure to dry, added 25 mL ethyl acetate to residual, extracted by ultrasound for 30 min, then filtered and added another ethyl acetate 25 mL to residual, extracted by ultrasound for 30 minutes again, combined extracts and concentrated to dry. The dry extract was added 50% ethanol to dissolve, transferred into a 10 mL volumetric flask, diluted to the mark, shaken well, then filtered and collected the filtrate.

The measurement method: reference solution and test sample solution were precisely sucked 10 [IL respectively, injected into the liquid chromatograph, then determined.

The content of Epimedii Fannin which was calculated by icariin (C331140015) was 32.22 jig/mL in Panax Notoginseng medicinal liquor prepared in example 1.

(3) Content Detection Method of psoralen and isopsoralen Psoralen and isopsoralen were determined by HPLC (Chinese pharmacopoeia version 2015 general rule 0512).

Chromatographic conditions and system suitability tests with chromatographic condition was C18 column, mobile phase A was methanol and mobile phase B was water, gradient elution followed the table below with flow rate of 1.0 m L/m in, at detection wavelength of 245 nm and temperature at 25 t, The number of theoretical plates calculated from the psoralen peak should be no less than 2000.

Time ninutes) Mobile phase A ( %) Mobile phase B ( % ) 0 50 50 50 50 90 10 90 10 Preparation of reference solution: the proper psoralen and isopsoralen were weighted accurately, added methanol to make a solution containing psoralen 20 jig/mL and isopsoralcn 20 ug/mL.

Preparation of test sample solution: the medicinal liquor was measured 10 mL precisely, adding to 0900 macroporous anion decolorizing resin chromatographic column ( d = I.2-1.5 cm, V = 20 cm3), eluted with 60 mL 50% ethanol and collected the eluent, concentrated under reduced pressure to dry, added 25 m L dithloromethane to residual, extracted by ultrasound for 30 minutes, then filtered and added another 25 mL dichloromethane to residual, extracted by ultrasound for 30 min again, combined extracts and concentrated to dry. The dry extract was added 50% ethanol to dissolve and transferred to a 10 mL volumetric flask, diluted to the mark, shaken well, then filtered and collected the filtrate.

The measurement method: reference solution and test sample solution were precisely sucked 10 jt1_, respectively, injected into die liquid chromatograph, then determined.

The content of Psoraleae Fruclus which were calculated by psoralen (CIIH603) and isopsoralen (CHH603) was 60.54 ug /m L in Panax Notoginseng medicinal liquor prepared in example 1.

(4) Examination of Long Chain Scorpion Venom Protein By SOS-PAGE Sample processing and addition: Scorpio and Eupolyphaga Seu Steleophaga were measured proper amount precisely, freeze-dried, added proper amount of standard molecular protein, added 5-fold 5X SDS-PAGE loading buffer, mixed well, boiled for 2-5 min, taken out and cooled down, the medicinal liquor was added 5X SOS-PAGE loading buffer, then transferred to an eppendorf tube and mixed, covered with a lid, heated for 2-5 mm in water bath with constant temperature (100 °C), and centrifuged (15000 xg) for 15 mm. Protein Marker and sample solution should be slowly added to the bottom of the sample hole with a micro injector of 5jd each.

Electrophoresis: motor plug was connected with the appropriate electrode and placed it in the freezer, set the voltage to 200 V and the current to 10 mA. When the sample has been entered the separation gel, set the voltage to 300 V and the current to 30 mA. When the leading edge of bromocresol blue dye have migrated to 1 cm from the bottom of the gel, stopped the electrophoresis. removed the gel glass plate from the electrophoresis tank, pried it open gently, removed the plastic, cleaned the gel with &ionized water, and removed the electrode buffer of the gel.

Staining and decoloring: gloves were wore, the gel was transferred into a large Petri dish which contained a small amount of coomassic brilliant blue, covered the lid, and shaken the stain slowly on a shaker (frequency: 40 -60 Hz, time: 2 -3 h.), discarded the stain, rinsed the gel several times in water, added decolorizing solution and decoloured overnight.

The results showed that the molecular weight of Pan ax Notoginseng medicinal liquor prepared in example 1 was less than 6.5 kDa.

(5) Content Detection Method of di-ester type of aconitine Di-ester type of aconitine was determined by HPLC (Chinese pharmacopoeia version 2015 general rule 0512).

Chromatographic conditions and system suitability tests with chromatographic condition was C18 column, mobile phase A was acetonitrile-tetrahydrofuran ( 25: 15) and mobile phase B was 0.1 mol/L ammonium acetate (adding 0.5 mL glacial acetic acid to per 1000 mL). gradient elution followed the table below with flow rate of 1 0 mumin, at detection wavelength of 225 nm and temperature at 25 "C: . The number of theoretical plates calculated from the aconitine peak should be no less than 2000.

Time (minutes) Mobile phase A (%) Mobile phase B (')/0) 0 15 85 48 26 74 49 35 65 58 35 65 15 85 Preparation of reference solution: the proper aconitine was weighted accurately, added phase A-phase B (15:85) to make a solution containing aconitine 50 mg /mL.

Preparation of test sample solution: the medicinal liquor was measured 50-100 m L precisely, added to D900 macroporous anion decolorizing resin chromatographic column ( d = 1.2-1.5 cm, V = 20 cm3), eluted with 60 mL 50% ethanol and collected the eluent, concentrated under reduced pressure to dry, added phase A-phase B ( 15: 85) 2 mL to residual, shaken well, then filtered and collected the filtrate.

The result showed that aconitine (C341447N010 was not detected in Panay Notoginseng medicinal liquor prepared in examplel.

EXAMPLE 5: EFFECT ON RHEUMATIC OSTEOPATHY ANIMALS Material: KM mice, were weighed 18 -22 g, SD rats, were weighed 180 -220g. The Panax notoginseng medicinal liquor used in the present invention was prepared in exam pie 1, whose content of ginscnoside Rgl was 0.20 mg/mL, icariin was 32.22 Rg/mL, psoralen and isopsoralen were 60.54 pg/mL, and aconitine was not detected. Besides, molecular weight of scorpion venom peptide was less than 6.5 kDa in the Fano' notoginseng medicinal liquor. Positive control (Pcmax notoginseng medicinal liquor supported by YUNNAN XITAO GREEN PHARMACEUTICAL CO. LTD, whose content of ginsenoside Rgl was 0.15 mg/mL, icariin was 30.61 ig/mL, psoralen and isopsoralen were 62.76 ug/mL, aconitine is 1.25 tg/nal_. Molecular weight of scorpion venom peptide was less than 20.1 kDa in this medicinal liquor.) The Pcmax nologinseng medicinal liquor was concentrated to the corresponding concentration by reducing pressure in 40 -50 °C before use.

(1) Hemolysin experiment in mice Normal mice group: 50 KM mice, half male and half female, were randomly divided into 5 groups (blank control group, positive control group, Panax notoginseng medicinal liquor model groups with low-dose, middle-dose and high-dose), 10 animals per group. The KM mice in positive control and model group were administrated the corresponding medicines by intragastric gavage. The KM mice in blank control group were administered liquor (concentration equal to that of the model group) by intragastric gay age at a dose of 10 mL/kg/d for 10 days. At the 3rd day of treatment, each KM mouse was sensitized by intraperitoncal injection with 0.2 mL 20% sheep red blood cells (SRBC). At 24 hours after the last intragastric administration, each mouse was taken blood 0.5 mL from the orbits, separated serum routinely and diluted by double dilution on a 96-well microtitre plate, 50 pl per well, added 50 p11% SRBC to each well and mixed, stored in 37 °C oven For 3 hours, observed the degree of agglutination of red blood cell, and calculated the serum antibody numerical value.

Immunocompromised mice group: 60 KM mice were administrated by the same method and injected intraperitoncally with 30 mg/kg cyclophosphamidc (CTX) on the 41' day and the Oh day (excepting blank control group mice), and calculated the serum antibody numerical value.

Antibody numerical value= (S1+2S2+3S3+ +nSn). In this formula, numberl, number2, number3 number n means index of double dilution, S means level of aggregation. The larger Antibody numerical value, the higher antibody levels in serum.

Level 0: all of red blood cells sink, concentrate at the bottom of the hole to form dots, and the liquid around is clear.

Level I: most of red blood cells sink to the bottom of the hole to form a dot, and there arc a few aggregated red blood cells around.

Level II: agglutinated red blood cells form a thin layer at the bottom of the hole, and a loose red dot can be clearly seen in the center.

Level agglutinated red blood cells spread evenly at the bottom of the hole to form a thin layer, and a small red dot is faintly visible in the center.

Level IV: agglutinated red blood cells spread evenly at the bottom of the hole to form a thin layer, and the clot is sometimes rolled.

Table 1 Effect of Panax notoginseng medicinal liquor on serum hemolysin in mice (X+s, n=10) group dose (g/kg) Antibody numerical value Normal mice Immunocompromised mice Blank control 126.5+34.4 38.5+24.0 Positive control 0.31 87.5+29.1A 65.3+26.7' Low-dose 0.16 93.9+31.8 50.9+24.1 Middle-dose 0.31 75.0+27.4A 66.0+23.1s High-dose 0.62 66.5+18.5A 67.4+20.5 A Compared to blank control group, AP<0.05, * P<0.01 For normal mice group, each dose of Pan ax notoginsc 7g medicinal liquor can reduce the Antibody numerical value. Besides, the value of middle-dose group and high-dose group were significantly lower than blank control group (P<0.05 or P<0.01), which means these dose of medicinal liquor have a certain inhibition of humoral immunity. However, when mice were injected CTX to decrease immunity, each dose group of Pan ax notoginseng medicinal liquor has a certain effect of increasing serum hemolysin. The value of middle-dose group and high-dose group were significantly higher than blank control group (P<0.01) in immunocompromised mice group, which means these dose of medicinal liquor have a certain enhancement of humoral immunity.

(2) Experiment of delayed type hypersensitivity in mice Testi 50 KM mice, was weighted 18 -22 g, half male and half female, were randomly divided into 5 groups (blank control group, positive control group, P CHICLY nologinseng medicinal liquor model groups with low-dose, middle-dose and high-dose), 10 animals per group. Each KM mouse was sensitized by subcutaneous injection in the back with 0.02 mL dinitrochlorobenzene acetone (DNCB) solution. Each group was administrated corresponding medicines by intragastric gav age at a dose or 20 mL/kg/d for 10 days. Thirty minutes after the last intragastric administration, the right ear of mice was challenged with 0.3 mL 1% DNCB sesame oil solution. After 24 hours, the animals were sacrificed, the left and right cars were cut, and removed two round pieces at the same location by a hole punch (diameter 9 mm), respectively. Two round pieces were weighed by the electronic balance to calculate the swelling degree (difference between right piece weight and left piece weight) of the auricle in the mouse, and calculate the swelling percentage (swelling degree / left ear's weight).

Test 2: 50 KM mice were operated in the same method as above. During the sensitization period, no administration was performed. The mice were administered by gavagc at 1 h and 13 h after challenge. After the experiment, swelling degree of the auricle of the mouse and swelling percentage were calculated, respectively.

Table 2 Effect of Pan ax nologinseng medicinal liquor on delayed hypersensil ity in mice (X±s, n=10) Groups dose (g/kg) Test 1 antibody titre level Test 2 blank control 3.07+1.64 3.31+1.80 Positive control 0.31 0.96+0.71A 2.66+3.90 A Low-dose 0.16 1.28+1.33 A 3.04+1.6A middle-dose 0.31 0.86+0.62" 1.9+2.7" high-dose 0.62 0.61+0.52" 1.3+2.2" Compared to blank control group, a.P<0.05, * P<0.01. Compared to positive control group, oP<0.05" NP<0.01.

Dosing after sensitization, Pan ax notoginseng medicinal liquor had a significant inhibitory effect on the delayed hypersensitivity induced by DNCB, which was statistically significant compared with die model group (P <0.05 or P <0.01). Each dose group of Puma nologinseng medicinal liquor could suppress delayed hypersensitivity induced by DNCB to a certain extent.

(3) Rat button granuloma experiment SD rats, were weighed 180 -220 g, were randomly divided into 5 groups (blank control group, positive control group. Pan ax notoginseng medicinal liquor model groups with low-dose, middle-dose and high-dose), 10 animals per group. Each rat was anesthetized with 4% pentobarbital (40 mg/kg) , fixed in supine position, removed hair from abdomen, sterilized with iodine and alcohol, cut from midsection of abdomen to both sides of groin, sutured incision. The incision was routinely sterilized, and the entire procedure was aseptically performed. Except the blank control group, the rats in the other groups were given the test drugs by gavage once a day for 10 days. 24 hours after the last administration, the rats were sacrificed. The granulation tissue of rats were taken out, weighed the wet weight, then placed in an 80 'C oven for 24 hours, then taken out and weighed the dry weight. The differences between the groups were compared and the inhibition ratio was calculated.

Inhibition ratio (%) = (dry weight of granulation in blank control group-dry weight of granulation in administration group) / dry weight of granulation in blank control group * 100% Both the middle-dose and high-dose groups of Ponca notoginseng medicinal liquor could reduce the dry weight of granulation tissue, which was statistically significant compared with the blank control group (P<0.05 or P< 0.01), Table 3 Effect of Panax notoginseng medicinal liquor on button granuloma (X±s, n=10) group dose (g/kg) Dry weigh (mg) Inhibition ratio (%) Blank control 252.7+30.5 Positive control 0.20 181.4±26.0A 28.2 Low-dose 0.10 182.4+25.3A 27.8 Middle-dose 0.20 176.0+25.0A 30.3 High-dose 0.40 165.5±27.0A 34.5 Compared to blank control group, AP<0.05, AP<0.01.

(4) Toe swelling experiment in rats male SD rats, were weighted 180 -220 g, were randomly divided into 5 groups (blank control group, positive control group, Pancrx notoginseng medicinal liquor model groups with low-dose, middle-dose and high-dose), 10 rats in each group. Except for the blank control group, rats in each group were given the corresponding test drugs by gavage once a day for 5 days. 1 h after the last administration, the rats were straighten hind limbs, injected a portion of the inflammatory agent (0.1% carrageenan 0.1 in L) from the middle of the toes subcutaneously by a needle NO.26, and then turned down the needles to inject the trace inflammatory agent. The thickness of the toes of rats was measured by a thickness gauge before the inflammatory agent and at 1, 2, 4, and 6 hours after the injection, and the differences between the groups were compared.

Panax nologinseng medicinal liquor has a significant inhibitory effect on toe swelling induced by carrageenan in rats.

Table 4 The effects of Panax nologinseng medicinal liquor on toe swelling (mm, X±s, n=10) group Dosc(g/k Before After injection injection lh 2h 4h 6h 8h Blank 0.20 0.10 0.20 0.40 5.12+0.31 5 13+0 29 5.12+0.23 5.13+0.26 5.11+0.26 5.54+0.14 5 53+0 37 5.54+0.26 5.47±0.18" 5.38+0.22 " 5.910.20 6.40+0.24 6.46+0.22 6 02±0 19A 6.27+0.21s 5.82±0.17A 5.53+0.17A 5.94+0.21A 6.51+0.12 control 5 52±0 301 5 98+0 21A 6 12+0 20k Positive 5.80±0.35A 6.07±0.221 5.550.19 A 6.26+0.20A control 5.510.301 5.500.20A 5.48+0.16A 5.64+0.16A Low-do se Middle-dose High-do se Compared to blank control group, AP<0.05, * P<0.01. Compared to positive control group. oP<0.05. NP<0.01.

EXAMPLE 6: LONG-TERM TOXICITY Materials: SD rats, were weighted 80 -100g. The Panax notoginseng medicinal liquor used in the present invention was prepared in example 1, whose content of ginsenoside Rgl was 0.20 mg/in L, icariin was 32.22 pg/m L, psoralen and isopsoralen were 60.54 pg/mL, aconitine was not detected. Besides, molecular weight of scorpion venom peptide was less than 6.5 kDa in the Panax notoginseng medicinal liquor. Positive control (Panax notoginseng medicinal liquor supported by YUNNAN XITAO GREEN PHARMACEUTICAL CO. LTD, whose content of ginsenoside Rgl was 0.15 mg/mL, icariin was 30.61 pg/m L. psoralen and isopsoralcn were 62.76 jtg/mL, aconitine was 1.25 pg/mL. Molecular weight of scorpion venom peptide was less than 20.1 kDa in this medicinal liquor.) The Panax notoginseng medicinal liquor was concentrated to the corresponding concentration by reducing pressure in 40 -50 "C before use.

Methods: 120 SD rats were randomly divided into 4 groups, 30 animals per group, half male and half female. The SD rats in blank control group were administered liquor (concentration equal to that of the model group) by intragastric gavage at a dose of 10 ml/kg/d. The SD rats in model group were divided into low-dose group, middle-dose group and high-dose group. Three groups were administered Panay notoginseng medicinal liquor by intragastric gavage at doses of 0.1 g/kg/d, 0.6 g/kg/d and 1.0 g/kg/d (calculated by crude drug amount), respectively. All of groups were observed behavioral performance, stool characteristics and other clinical signs once a day; weighted once a week, and adjusted the dose according to the change of rats' weight.

SD rats (half male and half female) were anesthetized (pentobarbital sodium, 80-400 mg/kg) in every group when this therapy were performed for 3 months, 6 months and stopped for 4 weeks, respectively. SD rats were taken blood from abdominal aorta to die, performed blood routine examination including Red Blood Cell Count (RBC), White Blood Cell Cotmt (WBC), Platelet Count (PLT), Hemoglobin (Hgb), blood biochemistry examination including Alkaline Phosphatase (ALP), Aspartate Transaminase (AST), Alan ine am inotransferase (ALT), Blood Urea Nitrogen (BUN) and Creatininc (Cr), dissected the heart, liver, spleen, lung, kidney and performed pathological examination.

The experiment result showed that there were no pathological changes in vital signs and hematology of the main organs and toes in each dose group of Panay notoginseng medicinal liquor. Three doses of the medicinal liquor did not affect the hematopoietic function of die rat bone marrow,and did not damage liver and kidney function in the rat. There was no obvious toxic target organs found in three dose groups. The experiment suggest that there is no adverse reaction of the Panaxnologinseng medicinal liquor at a high dose of 1.0 g/kg/day in rats, and rats have no toxic side effect after continuous intragastric administration for 6 months. It can provide a reference for clinical trials.

Table 5 Results of blood biochemical indicators in SD rats after 3 months administration biochemical indicators Blank control Low-dose Middle-dose High-dose male 176.8+22.9 183.4+25.0 176.6+25.5 145.0+26.9 AST (IU/L) female 162.1+23.4 168.8+23.2 164.5+26.6 137.9+26.2 ALT (IU/L) male 51.4+11.5 50 6+10 3 49.9+10.6 46.4+14.3 ALP (IUM) female 40.8+7.7 43.0+10.9 38.614.3 35.8+13.0 male 147.2+16.9 142.1+14.6 152.5+15.9 161.6+11.9 female 136.6+15.7 135.3+16.5 142.0+13.6 151.7+17.9 male 58.7+8.9 59.2+6.9 57.3+4.1 60.9+2.3 TP (g/L) female 60.0+5.9 58.3+7.9 58.5+2.9 64.0+3.8 male 34.1+9.1 33.1+4.8 33.2+7.6 35.9+8.4 ALB (g/L) female 36.1+7.1 35.3+4.3 35.9+8.9 36.9±9.1 male 4.91+6.56 5.76+14.90 5.63+8.88- 5.64+13.43 BUN (mmol/L) female 5.91+14.35 5.89+15.90 5.94+11.78 5.91+13.09 male 5.26+0.40 5.27+0.49 5.29+0.26 5.28+0.42 Glu (mmol/L) female 5.59+0.62 5.66+0.98 0.640.81 5.661.29 male 50.2+3.1 49.8+2.9 49.1+2.3 50.2+1.8 Cr (gmol/L) female 50.2+3.9 50.3+2.4 50.0+3.6 49.9+4.5 male 1.50+0.47 1.50+1.19 1.49+0.81 1.50+1.02 Tc (mmol/L) female 1.51+0.99 1.50+0.73 1.49+0.62 1.49+0.67 Compared to blank control group, AL<0.05, *P<0.01.

Table 6 Results of blood biochemical indicators in SD rats after 6 months' administration biochemical Blank control Low-dose Middle-dose High-dose indicators AST (IU/L) male female male female male female male female male female male female male female male female male female 182.1+24.2 163.2+18.8 51.2+10.3 39.6+9.6 149.1+16.5 139.4+16.3 58.5+4.6 59.6+7.5 36.5+6.9 34.2+7.3 5.53+11.83 5.73+19.75 5.28+0.37 5.65+1.08 49.8+3.0 49.4+4.0 1.50+0.28 1.50+0.79 198.2+22.3 182.6+19.5 49.3+10.4 40.3+12.9 138.2+17.4 127.4+8.9 60.9+7.6 59.0+5.8 38.1+6.4 37.5+3.8 5.34+17.68 5.18+14.90 5.28+0.54 5.63+1.43 48.7+2.1 50.8+2.9 1.50+0.78 1.50+0.60 179.2+20.6 162.4+22.4 47.3+13.3 38.7+16.9 156.7+14.6 148.0+15.0 58.9+6.1 59.5+6.7 33.5+11.6 35.2+9.5' 5.92+4.98 5.24+5.19 5.27+0.44 5.60+0.77 49.9+3.4 51.1+1.5 1.49+0.73 1.51+0.34 156.1+20.0 150.3+22.6 45.4+13.0 32.4+11.2 167.2+10.8 161.8+18.5'1 59.0+5.9 60.4+10.5 35.1+7.3 36.5+10.9 5.61+11.74 5.92+12.67 5.29+0.30 5.66+1.02 49.9+3.0 50.1+2.7 1.4910.48a 1.49+0.94 ALT (1U/L) ALP (I U/L) TP (g/L) ALB (g/L) BUN (mmol/L) Glu (mmol/L) Cr (pmol/L) To (mmol/L) Compared to blank control group, AL<0.05, *P<0.01.

Table 7 Results of blood biochemical indictors in SD rats after recovery biochemical Blank control Low-dose Middle-dose High-dose indicators male 176.2+17.3 173.1+19 176.0+16.9 180.9+19.5 AST (IU/L) female 164.4+18.5 162.7+21. 168,1+15,7 161.7+22.2 male 50.0+11.7 50.5+11.8 51.5+13.4 49.2+37.6 ALT (IU/L) female 39.9+9.3 40.5+15.0 40.4+15.2 37.6+16.8 male 147.8+14.8 143.5+18. 145.2+16.0 146.3+15.8 ALP (IU/L) Female 132.4+15.8 135.6+16 132.1+17.8 133.1+12.5 male 63.4+3.2 58.3+8.1 58.3+6.0 59.4+8.6 TP (g/L) female 59.1+10.2 59.8+8.4 59.6+7.7 59.5+3.1 male 34.3+5.0 35.1+9.2 35.0+5.5 36.9+7.1 ALB (g/L) female 32.2+2.5 36.4+9.0 32.9+1.1 36.8+9.3 male 5.89+5.42 5.37+15.9 5.98+8.42 5.71+12.49

I

BUN (mmol/L) Female 6.01+11.45 5.73+16.2 5.73+12.19 5.39+9.81 male 5.27+0.27 5.27+0.22 5.28+0.58 5.28+0.53 Glu (mmol/L) fern ale 5.63+0.76 5.65+1.60 5.66+1.19 5.63+1.01 male 50.6+3.2 50.6+3.0 49.5+2.3 50.2+2.6 Cr (mon) female 50.2+2.7 49.6+3.6 48.9+2.9 49.7+3.4 male 1.50+0.59 1.50+0.63 4.50+0.84 1.51+0.41 To (mmol/L) female 1.50+0.78 1.49+0.67 1.49+0.88 1.50+0.86 Compared to blank control group, AP<0.05, *P<0.01.

Claims

Cl aim s: 1. A preparation procedure of orally taken Pcmax notoginseng medicinal liquor for treating rheumatic ostalgia, with the Pcmax notoginseng medicinal liquor prescription comprising parts by weight of 50 parts of Notoginseng Radix et Rhizome, 40 parts of Curctunae Rhizoma, 10 parts of Scorpio. 30 parts of Eupolyphaga S'eu Steleophaga, 50 parts of Psorctleae FrUCEUS 50 parts of Epimedii Folium, 60 parts of Henry chloranthus. herb, 80 parts of Herba Ainshaeae, 60 parts of Angel/cue sinensis Radix, 50 parts of Achyranthis Bidentatae Radix, 60 parts of Acanthopanacis Cortex, 20 parts of Aconiti Radix cocta, 40 parts of Sappan lignum, 60 parts of Sargentodoxae can/is, 30 parts of Chuanxiong Rhizoma, 10 parts of Draconis Sanguis, 20 parts of Carthami parts of Oiihamm (processing with vinegar), 30 parts of Myrrha (processing with vinegar), 40 parts of Rhizome Corydalis (processing with vinegar), 40 parts of Cyperi Rhizoma (processing with vinegar), comprising the following steps: (1) crushing the Scorpio and the Eupolyphaga Seu Steleophaga into coarse powders. adding 0.8 -2 volumes of 30% -50% Chinese white liquor to extract the coarse powders, adding 0.08% -0.12% weight of the coarse powders bromelain at 50 -60t, infiltrating and dissolving for 3 -5 hours, performing purification in Superdex peptide column, eluting with 1 -2 volumes of 30% -50% Chinese white liquor and discarding the eluent, then eluting with 2 -4 volumes of 30% 50% Chinese white liquor and collecting the eluting solvent to reserve; (2) crushing the Aconiti Radix coda, Henry chloranihus herb, Herba Ainshaeae, Cyperi rhizoma, Chuanxiong Rhizoma into coarse powders, adding those coarse powders into percolation apparatus, adding reserving eluting solvent prepared in step (1) and 1 -2 volumes of 50% -60% Chinese white liquor, soaking hermetically at room temperature for 12 -36 hours, then crushing the remaining medicinal materials into coarse powders, adding those coarse powders into the above percolation apparatus, adding 3 -7 volumes of 50% -60% Chinese white liquor, soaking hermetically for 10 -20 days with light-proof packing materials; (3) adjusting flow rate of percolation to 3 -5 ml/(min-kg), adding 50% -60% Chinese white liquor constantly, collecting 8400 mL percolate for each prescription, resting the percolate, then filtrating through filter plate with particle size of 74 t.im to yield Panax notoginseng medicinal liquor.
2. A preparation procedure as claimed in claim 1, wherein the extraction solvent in step (1) is 1.5 volumes of 40% Chinese white liquor, the eluting solvent in step (1) is 3 volumes of 40% Chinese white liquor.
3. A preparation procedure as claimed in claim 1, wherein the amount of bromelain added in step (1) is 0.10% weight of the coarse powders.