CN1994352A - Use of total glucosides extract of cocklebur fruit in preparation of product for resisting inflammatory reaction - Google Patents
Use of total glucosides extract of cocklebur fruit in preparation of product for resisting inflammatory reaction Download PDFInfo
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Abstract
The invention relates to an application of xanthostrumarin extractive, wherein said xanthostrumarin extractive comprises diterpene compound, phenolic acid compound and other extractives while their contents are 0.5%-99%, 0.5%-99%, and 0.5%. And the production uses general extraction, separation and purification. The extraction is solvent extraction method; the separation and purification uses solvent extraction method and porous adsorption resin method. The inventive extractive can treat coryza, nasal sinusitis, etc. It has simple production and stable property.
Description
The application is dividing an application of application for a patent for invention " Fructus Xanthii total glucosides extract being used to prepare the purposes of anti-inflammatory response product ", the applying date of original application is on 03 28th, 2005, application number is 200510024693.9, and invention and created name is: Fructus Xanthii total glucosides extract is used to prepare the purposes of anti-inflammatory response product.
Technical field
The present invention relates to medicine, food, technical field of beverage, specifically relate to the purposes of Chinese medicine extract, more particularly relate to the purposes that the Chinese medicine Fructus Xanthii total glucosides extract is used to prepare the anti-inflammatory response product.
Background technology
(1) research overview of Fructus Xanthii
1, plant resources and application scenario
Fructus Xanthii (Fructus Xanthii), fruit for the drying and ripening band involucre of feverfew Herba Xanthii (Xanthium sibirium Patr.), have another name called that wild eggplant, sheep band is returned, Indian Skullcap Herb, thorn class, sticking certain herbaceous plants with big flowers, grey son etc., be the Chinese Pharmacopoeia kind, China all produces in most of area, and resource is extremely abundant.The traditional Chinese medical science is thought its acrid in the mouth hardship, warm in nature, returns lung, liver two warps, has diaphoresis, an effect of loose rheumatism, clearing the nasal passage, pain relieving.Tradition is used for the treatment of headche due to wind-cold, the nasal sinusitis watery nasal discharge, and the rubella pruritus, arthralgia chiefly caused by damp pathogen contracture etc. (Pharmacopoeia of People's Republic of China committee. Pharmacopoeia of People's Republic of China [S]. one one. Beijing: Chemical Industry Press, 2000:128); Modern clinical treat with it dermatosiss such as acute and chronic rhinitis, sinusitis, tracheitis, lumbago and skelalgia and rubella, mange (State Administration of Traditional Chinese Medicine. China's book on Chinese herbal medicine [M]. the 7th. Shanghai: Shanghai science tech publishing house, 1999:1013-1016).
2, chemical constituent
Studies show that the contained chemical constituent of cocklebur mainly is sesquiterpene lactones, volatile oil and water solublity glycoside, division is as follows:
(1) mainly contains the guainane type in the sesquiterpene lactones chemical compound cocklebur and split guainane type lactone compound, mainly contain xanthinin (xanthinin, promptly latent Herba Xanthii lactone), xanthumin (xanthumin, it is the Herba Xanthii lactone, stereoisomer for xanthinin), Herba Xanthii booth (xanthatin, i.e. xanthinin) and their derivant etc.Also have xanthanol (xanthanol), xanthinosin in addition, and the xantholide A among the X.canadense, xantholide B, pungiolide A among ziniolide among the X.catharticum, lasidiol p-methoxybenzoate and the X.pungens, multiple chemical compound (Salinas-A such as pungiolide B, De-Ruiz-RE, Ruiz-SO.Sterols, flavonoids and sesquiterpenic lactonesfrom Xanthiun spinosum (Asteraceae) .Acta Farm Bonaerense, 1998,17:297; And Kis-I, Racz-G.Glycoside contents of sitosterol from leaves of Xanthiun spinosum and X.italicum.FarmaciaBucharest, 1988,36 (1): 55; And Ahmed-AA.New vomifoliol derivative from Xanthiun pungens.Pharmazie, 1990,45:698).
(2) volatile oil Ahijja-MM etc. extracts volatile oil (Ahijja-MM in the Herba Xanthii X..strumarium leaf with steam distillation, Nigam-SS.Chemical examination of the essential oil from the leaves of Xanthiunstmmarium (Linn.) .Flavour Ind, 1970,1:627), discovery contains d-limonene (d-limonene, 35%), p-Cymene (p-cymene, 5%), β-Flos Caryophylli alkene (beta-caryophyllene, 6%), terpinolene (terpinolene, 7.3%), 1-α-Zi Luolantong (1-alpha-ionone, 10.9%), the high terpene alcohol of d-(d-carveol, 25%) and australene (alpha-pinene, 0.4%).Taher-HA etc. have analyzed the volatile oil component (Taher-HA among the X.cavanillesii, Ubiergo-GO, Talenti-ECJ.Constituents of the essential oil of Xanthiun cavanillesii.J Nat Prod, 1985,48:857.), wherein contain monoterpene hydrocarbon 55.2%, the monoterpenoid 14.2% of oxidation, sesquiterpene hydro carbons 11.3%.Guo Yahong etc. from the volatile oil of Fructus Xanthii, analyze 17 chemical constituents and calculated its relative percentage composition (Pan Jiongguang is etc. the research of volatile oil in the Fructus Xanthii for Guo Yahong, Li Jiashi. CHINA JOURNAL OF CHINESE MATERIA MEDICA, 1994,19 (4): 235).
(3) water solublity glycoside Song Zhen jade etc. has been isolated a kind of material (AA2 by name temporarily) with glycoside character from the water logging agent of Fructus Xanthii as far back as the sixties in last century, may be the main toxic component (Song Zhenyu of Fructus Xanthii, Zhang Lingyun, thank to wisdom, Deng. toxic component of Fructus Xanthii and pharmacological action thereof. Acta Pharmaceutica Sinica, 1962,9 (11): 678).MacLeod-JK etc. extract from the bur of noogoora burr X.pungens and have obtained two kinds of deleterious kaurene glucosides of water solublity (kaureneglycoside) constituents (MacLeod-JK, Moeller-PD, Franke-FP.Two toxic glycosides from the burrs ofXanthiun pungens.J Nat Prod, 1990,53:451), identify through two dimensional NMR and mass-spectrometric technique, determine that its structure is the derivant of carboxyl atractyloside (carboxyatractyloside).In addition, also from Fructus Xanthii and Herba Xanthii mongolici, extract with a kind of water solublity poison glycosides, through be accredited as atractyloside (atracyloside) (Sun Zeren is etc. the toxic component in the Herba Xanthii mongolici kernel for Wang Suxian, Ren Lijuan. Chinese herbal medicine, 1983,14 (12): 1).
(4) also contain xanthostrumarin (strumaroside, i.e. cupreol glucoside), 8-(Δ 3-isopentene group)-5,7,3 ' in other Herba Xanthiis, 4 '-kaempferol, and caffeic acid and 1, the 4-dicaffeoylquinic acid.In addition, still contain alkaloid, tannin, chalcone derivative, triterpenoid compound, glucose, fructose, aminoacid, tartaric acid etc.
3, pharmacologically active
(1) anti-microbial effect Fructus Xanthii decoct has stronger inhibitory action external to multiple microorganisms such as staphylococcus aureus, anthrax bacillus, streptococcus pneumoniae, group B streptococcus and diphtheria corynebacteriums.Fructus Xanthii acetone or alcohol extract is to trichophyton purpureatum, and its water extract has antifungic action to trichophyton.Open and just equaling to studies confirm that in 1988 the Fructus Xanthii decoct is 25%～50% at external direct suppression ratio to the hepatitis B virus DNA polysaccharide, show that it has the hepatitis virus resisting effect (just opening, permitted eastwards, Du Shaocai, experimentation Deng .60 kind Chinese herbal medicine anti-hepatitis virus. journal of Beijing Medical University, 1988,20 (3): 211).
(2) the effect Fructus Xanthii decoct to cardiovascular system has inhibitory action to isolated frog heart and guinea pig heart, makes decreased heart rate, and heart contractility weakens, and can expand rabbit ear blood vessel, frog blood vessel is then expanded after-contraction earlier, and the Fructus Xanthii injection can make rabbit and the of short duration decline of dog blood pressure.Glycoside composition AA2 has slight hypotensive activity to rat, and can strengthen vascular permeability (Song Zhenyu, Zhang Lingyun thank to wisdom, etc. toxic component of Fructus Xanthii and pharmacological action thereof. Acta Pharmaceutica Sinica, 1962,9 (11): 678).
(3) to the effect Fructus Xanthii extract (being equivalent to crude drug 0.2g/ml) of blood system can significant prolongation thrombin of beef cohesion human fibrinogen time, obvious antithrombase effect is arranged.The Fructus Xanthii methanolic extract can recover the reduction because of rabbit cholesterol due to the fasting and triglyceride rapidly, also can make content of phospholipid that to a certain degree rise is arranged.
(4) the Immune Effects Fructus Xanthii all there is obvious inhibitory action to cellular immunization and the humoral immune function of the purebred mice of C57/BL.Fructus Xanthii makes auxiliary type T cell, and (be called for short: TH) (be called for short: TS) cell number reduces, and TH/TS ratio is reduced with inhibition type T cell.Fructus Xanthii all has remarkable reduction effect to the beta-endorphin in hypothalamus and the blood plasma.In addition, Fructus Xanthii still can reduce interleukin II and (be called for short: IL-2) active and IL-2 content receptor, can obviously reduce the release of histamine in the cell, this can be used for one of mechanism for the treatment of anaphylactic disease (Wang Longmei for Fructus Xanthii, Fu Huidi, Zhou Zhilan. Fructus Lycii, the Rhizoma Atractylodis Macrocephalae, Herba Asari, Fructus Xanthii are to the influence of interleukin II expression of receptor. Chinese clinical pharmacy magazine, 2000,9 (3): 172).
(5) the antioxidation Fan Jing slope antioxidation of studying Fructus Xanthii in 1994, show Fructus Xanthii decoct 0.5g crude drug/only irritate stomach, every day 1 time, continuous 10d, can reduce lipid peroxidation effectively, reduce and organize lipid peroxide (to be called for short: LPO) content, (be called for short: SOD) activity has raising trend to superoxide dismutase, show the removing ability of Fructus Xanthii energy enhancing body to free radical, the infringement of minimizing radical pair body (Fan Jingpo. Fructus Xanthii, Herba Asari, Fructus Lycii, the Rhizoma Atractylodis Macrocephalae is to the influence of mouse tissue Radical Metabolism. Chinese medicine information, 1994, (2): 48).
(6) antiinflammatory and analgesic activity Liu Qing increase etc. 1988 pharmacologically actives of having set forth Fructus Xanthii extract (Liu Qingzeng, Wang Jinlan. Japan is to some progress of Chinese medicine pharmacological research in recent years. Pharmacology and Clinics of Chinese Materia Medica, 1988,4 (2): 50).Fructus Xanthii methanolic extract 250mg/kg lumbar injection is to the bullate suppression ratio 30%～60% of rat carrageenan foot; The 1000mg/kg subcutaneous injection, the suppression ratio that the mice acetic acid twisting is reacted is 10%～30%, shows that this product has certain antiinflammatory and analgesic activity.Add flavor Fructus Xanthii ball and have good antiinflammation, comprising: can significantly reduce acetic acid induced mice abdominal cavity azovan blue seepage discharge, can significantly reduce the swelling degree of dimethylbenzene induced mice otitis disease.Still have good analgesic activity, but significant prolongation acetic acid induced mice writhing response time of occurrence (Ma Ping, Li Hong. the progress of Fructus Xanthii. Chinese herbal medicine, 1999,30 (8): 634).
(7) other there are some researches show that also the Fructus Xanthii water extract reaches 50%～70% at external suppression ratio to cervical cancer cell; Fructus Xanthii extract (is called for short: HMG-Co-A), calcium channel blocker receptor and cholecystokinin etc. have inhibitory action in various degree angiotensin receptor, beta-hydroxy-Beta-methyl 1,3-propanedicarboxylic acid coenzyme A.
4, the clinical practice of folk prescription and compound recipe (Li Hong, week scheme, the pharmacological action of Fructus Xanthii and compound preparation and clinical progress. Mountain Western Medicine S University's journal, 2004,35 (3): 313-314)
(1) treatment cacorhinia
Treatment rhinitis chronic rhinitis is a kind of commonly encountered diseases, frequently-occurring disease.Someone is the plus-minus sanction on the basis of former Fructus Xanthii powder, and at random 96 routine patients are divided into treatment group and matched group, 1 month is 1 course of treatment, clinical observation, there was no significant difference between two groups, add flavor Fructus Xanthii pill for curing chronic rhinitis and ' Biyanwan ' for treating rhinitis near and be better than ' Biyanwan ' for treating rhinitis slightly.
The treatment sinusitis is closed Fructus Xanthii powder treatment chronic sinusitis with Radix Scutellariae Decoction, clinical observation 108 examples, and total effective rate 94.4%, can obviously take effect a course of treatment after the general medication.It is remarkable to share treatment chronic sinusitis in children effect with Fructus Xanthii mixture and hismanal.Fructus Xanthii bakes into brown back levigation or powder system honeyed pill, treatment of allergic rhinitis, and most of patients transference cure or improvement, or outbreak reduces.Also useful ancient prescription Fructus Xanthii powder adds treatment chronic sinusitis 67 examples such as Fructus Chebulae, Pheretima, 42 examples of fully recovering, 20 examples that take a turn for the better, invalid 5 examples, total effective rate 92.54%.
The treatment nasal sinusitis traditional Chinese medical science is classified as nasal sinusitis with acute purulent nasosinusitis.With Fructus Xanthii mixture treatment acute purulent nasosinusitis 200 examples, treatment is organized 100 examples and is taken the Fructus Xanthii mixture, and matched group 100 examples are selected symptomatic treatments such as penicillin, bactrim for use.Clinical treatment is the result show, treatment group and matched group total effective rate are respectively 99% and 95% (P＞0.05), no significant difference.Grey, hot decoct also commonly used is clinically treated nasal sinusitis and allergic rhinitis, and the report of also useful jade screen Fructus Xanthii powder treatment of allergic rhinitis etc. have all illustrated the contribution of Fructus Xanthii in the treatment cacorhinia.
(2) treatment cancer Fructus Xanthii becomes compound preparation with different prescription forms, effectively cures many cases nasopharyngeal carcinoma, tumor of nasal cavity clinically; Treatment carcinoma of penis 3 examples, and cooperate the operation clinical cure; And treat intracranial tumor, nervous system malignant tumor, cerebroma etc. and all play certain curative effect.
(3) treatment odontopathy bibliographical information is treated intractable toothache 98 examples, satisfactory effect with folk prescription handed down from one's ancestors.Also useful Fructus Xanthii, each 15g of Radix Scrophulariae add and are decocted in water for oral dose, the treatment medicable report of having a toothache.
(4) treatment dermatitis 25 examples (accounting for 65.8%) of in 38 routine dermatitis patients, fully recovering, produce effects 10 examples (accounting for 26.8%), invalid 3 examples (accounting for 7.9%), total effective rate 92.1%.
(5) out-patient of treatment upper respiratory tract infection bibliographical information 30 routine upper respiratory tract infection uses to add the flavor Herba Xanthii in treating, 26 examples of fully recovering (accounting for 86.7%), 3 examples that take a turn for the better (accounting for 10.0%), invalid 1 example; Total effective rate reaches 96.7%.Take medicine minimum 2 doses, maximum 5 doses.
(6) treatment diarrhoea Herba Xanthii is in about 50g～70g, and after adding the 3000ml clear water and soaking 30min, the back reuse 15min at a simmer that is fried boiling with high heat leaches medicinal liquid, and is cool to 35 ℃～38 ℃, with warm liquid dipping bath or immersion shank and sufficient every day 3 times; Cure 46 examples, cure rate is 95.77%, effective 1 example, and effective percentage is 2.15%, invalid 1 example (accounting for 2.15%).
(7) the treatment otitis media has bibliographical information to adopt Herba Xanthii to cooperate antibiotic xeraphium treatment simple type suppurative otitis media to receive excellent curative in loosing clinically.
(8) treatment typhoid fever Herba Xanthii was soaked heated and boiled 1h in 6000g with clear water, leached decocting liquid, fry in shallow oil 3 times with connecting with quadrat method, 3 decocting liquids are mixed, filter, slow fire is concentrated into 2000ml, add nipalgin 10g, shake up, effectively treat typhoid fever 15 examples, the fastest 10h of fever time, 7 routine blood, excrement, bile Bacillus typhi positive person all turn out cloudy after the treatment.
(9) the bright Herba Xanthii of treatment dysentery is cleaned and mashes in 100g, adds decocting 15min, removes slag, and squeezes into 2～3 in egg, in medicinal liquid, boil, before outbreak with medicinal liquid and egg with clothes, do not heal for 1 time, the method that can connect is obeyed again, it is good to treat the dysentery curative effect.
(10) treatment furuncle Herba Xanthii is in, Fructus Arctii, Radix Et Rhizoma Rhei etc., and 1 dose of every day, decocting divides clothes 2 times; Example surplus the 4-8 agent continuously, treatment furuncle 30 all obtains good effect.
(11) other clinical practices utilize in addition clinically Herba Xanthii in and the report of compound preparation treatment lumbago and skelalgia, parotitis, ulcer of the lower limb, all received certain curative effect.
Fructus Xanthii is singly used clinically or forms compound recipe with other Chinese medicines, be used for the treatment of the common and difficult and complicated illness of nose section such as acute and chronic rhinitis, sinusitis and allergic rhinitis, all obtained curative effect preferably, as " grey hot nasal drop ", " Fructus Xanthii powder ", " Herba Xanthii Radix Angelicae Sinensis drink ", " grey hot fish root of Dahurian angelica soup " etc., all be hot and suffocating clearly, removing dampness is turbid, open the famous prescription of nose key, used for many years clinically, curative effect is better.But because to its chemical constitution study not deeply, the pharmacological screening deficiency causes active site and active component indeterminate and do not have feasible quality standard, has limited the further development and utilization of Fructus Xanthii.
(2) progress of sinusitis
Sinusitis (sinusitis) is because antibacterial is invaded nasal sinuses, destroys sinus tissue, the acute or chronic inflammatory disease that causes nasal sinuses to take place.Site of pathological change is the highest with the sickness rate of maxillary sinusitis, secondly is ethmoiditis, frontal sinusitis and sphenoiditis, and getting involved as all nasal sinuses then is called pansinusitis (pansinusitis).
Acute and chronic sinusitis is a kind of commonly encountered diseases and frequently-occurring disease, and according to the literature, only just there are 3,700 ten thousand chronic sinusitis patients in the U.S.; Some American Studies personnel think that global sinusitis patient accounts for 14% (about 800,014,000 populations) of world's total population, and the case load of sinusitis is year by year all in quick increase.In China, because the region difference, various places sinusitis sickness rate fluctuates between 10.7%～44.5%.According to the clinical data statistics, chronic sinusitis morbidity number accounts for department of otorhinolaryngology first visit patient's 13.02%.Especially in southern area of China, owing to have a humid climate, the sinusitis sickness rate is very high, having approximately more than 1/3 among the first visit patient of Shanghai Changhai Hospital department of otorhinolaryngology outpatient service is all kinds of sinusitis patients, wherein patient age accounted for 76.0% below 30 years old, there be 6.4%, 50 years old between 40～50 years old and still have 1% or 2% later on.
Since the hole stenostomy, factors such as unfavorable drainage and allergic constitution, primary disease Chang Fanfu outbreak, delay is difficult.And should the disease course of disease long, often again with symptoms such as headache, dizziness, hypomnesis, thereby bring utmost point adverse effect for patient's study, work, life.
In addition, after sinusitis took place, inflammation can be expanded the infringement adjacent tissue, very easily causes osteomyelitis, eye socket cellulitis, piitis, brain abscess, and serious purulent sinusitis even also can cause septicemia directly jeopardizes patient's life.Repetitious stimulation that there are some researches prove chronic sinusitis also can cause canceration.
Modern study shows that chronic sinusitis is by the coefficient result of multiple factor, and still wherein many factors still fail to be understood by people, and its pathogenesis is not illustrated as yet fully.In external scholar the research of its pathogenic factors is mainly concentrated on the following aspects: 1. antibacterial or viral infection; 2. hole mouth nasal meatus complex (is called for short: OMC) block; 3. mucomembranous cilium dysfunction; 4. immunologic function disorder etc.
The pathogenic bacterium of sinusitis morbidity mostly are pyococcus, as Diplococcus pneumoniae, haemolysis type streptococcus, staphylococcus etc., are bacillus secondly, as hemophilus influenza, Bacillus proteus etc.The generation of sinusitis is most because due to two kinds of pathogenic bacteria mixed infections clinically.The intrusion of antibacterial makes host resistance impaired, and the nasal mucosa fibre function reduces, even makes the defense mechanism paralysis of mucosa.
Hole mouth nasal meatus complex that studies show that in recent years, a variety of causes are caused block cause ventilation and drain obstacle be cause the sinusitis protracted course of disease and the main diseases of showing effect repeatedly because of.Simultaneously, above-mentioned each link is not isolated the existence, but influences each other, interacts, and has caused persistence inflammatory reaction of nasal sinuses mucosa and irreversible pathological change.
The sickness rate height of sinusitis, inflammation easily expansion cause severe complications, and easily outbreak repeatedly, and delay is difficult.Western medicine at present commonly used clinically mainly is antibiotic, go congested agent, the agent of reducing phlegm, analgesic, steroid and nasal spray etc., be only applicable to light disease and early stage patient and preoperative patient, and majority can only improve symptom in various degree, and sinusitis thoroughly can't be effected a radical cure.Side effect in various degree can appear in about 2/3 sinusitis patient in external or after taking these Western medicine, as modal be the ephedrine nasal drop, prolonged and repeated use can cause nasal cavity vasomotion dysfunction, and the degeneration slightly of nervi olfactory end forms medicamentous rhinitis at last; The antibiotic abuse then makes pathogenic bacterium produce drug resistance easily, also may destroy the balance of normal flora, makes it imbalance, causes adverse consequences.In sum, though the medicine of treatment sinusitis is many on the market, curative effect instability, in various degree drawbacks limit such as side effect have been arranged its application clinically.
(3) progress of inflammation
Exogenous damage factor and endogenous damage factor all can cause the various damaging pathological changes of cell, meanwhile complex series of reactions then takes place in the part of body and whole body, with limitation with eliminate these damage factors, removing and absorption slough, cell, and repair and damage, the defensive reaction of Here it is body, i.e. inflammation (inflammation).
The local Clinical symptoms of inflammation is red, swollen, pain and dysfunction, and the caused general reaction of inflammation comprises that heating and tip blood leukocytes are counted and increases.Inflammation is the first line of defence that health is resisted viral infection originally, is the protection to health.But serious or when developing into chronic inflammatory disease when degree of inflammation, it just might cause heart attack, colon cancer and a series of other diseases of senile dementia disease etc. morning.
Clinical anti-inflammation analgesia medicine commonly used is mainly nonsteroidal antiinflammatory drug (abbreviation: NSAIDs) at present.NSAIDs has been widely used in rheumatoid disease patient and non-rheumatism patient's analgesia, comprises abdominal pain and menstrual pain such as acute postoperative pain, chronic pain, biliary colic and renal colic.Traditional nonsteroidal anti-inflammatory drug the infringement of gastrointestinal tract, coagulation function and renal function aspect occurs inevitably because of the increase of dosage, the course of treatment and patient age, has restricted its range of application.
NSAIDs mechanism of action: be the activity that suppresses Cycloxygenase (cyclooxyRenase) COX, thereby reduced the synthetic of prostaglandin PGs, reach the effect of anti-inflammatory analgesic.The COX enzyme has two kinds of isozymes, the COX-1 of basal expression, and major function is to keep the normal physiological function of gastrointestinal, kidney and other organs; The COX-2 of abduction delivering can find in brain and inflammation part and play a role.The antiinflammatory action mechanism of NSAIDs thinks to have suppressed COX-2, and untoward reaction is because suppressed COX-1.
Non-specific NSAIDs class medicine commonly used such as ibuprofen (ibuprofen), naproxen (naproxen), diclofenac sodium etc. are long and narrow because of structure, there is not selectivity, can combine with the active site of COX-1 and COX-2 simultaneously, both can suppress COX-1, can suppress the activity of COX-2 again.Thereby existing anti-inflammatory analgesic action, with untoward reaction such as gastrointestinal tract, coagulation function and renal function are arranged often.
The subject matter of NSAIDs treatment is untoward reaction.Along with increasing progressively of age, untoward reaction is remarkable more, comprises gastrointestinal tract, kidney, cardiovascular system, central nervous system.
(4) progress of viral disease and treatment thereof
According to statistics, 60%～65% epidemic infectious diseases is caused by viral infection.The 7th part of virus type journal that propose in world's virusology conference that Paris, FRA is held in August, 2002 accused and pointed out to make human disease's virus that 29 sections are arranged, 7 subfamilies, and virus is planted in 53 residences more 1200.Sickness rate height, the viral disease that hazardness is big have 6 kinds, as the acute, chronic hepatitis due to the hepatitis virus; 8 kinds of cytomegalovirus (abbreviations: CMV) retinitis, interstitial pneumonia, herpes simplex encephalitis, eye keratitis, genital herpes, herpes zoster, herpes labialis that the herpes virus hominis causes; Bronchitis, pneumonia, measles, parotitis, poliomyelitis that respiratory virus infection causes; Acute gastroenteritis and infantile diarrhea etc. and human immunodeficiency virus due to the enterovirus (be called for short: the acquired immune deficiency syndrome (AIDS) HIV) (be called for short: AIDS) or the like.
Though from being familiar with viral first day, human just the searching constantly resisted viral effective weapon, the treatment of viral disease, the present strong medicine of specificity that still lacks.Chang Yong medicine has following a few class clinically: the antiviral agents that 1. suppresses virus replication; 2. the immunity regulatin remedy medicine of enhancing human body immunity function; 3. at the cough-relieving of clinical symptoms, ease pain, bring down a fever and curative such as antiinflammatory; 4. prevent the anti-infective of secondary infection; 5. the vaccine of prophylaxis of viral infections; 6. the disinfectant propagated of blocking virus etc.
(5) analgesic progress
Pain is human total and the very big a kind of impression of individual variation is the alarm signal that health and internal organs suffer damage.Because pain is normal and autonomic nerve activity, psychology and emotional response weave in, and great variability is arranged, and therefore feels more difficult research than other.People are to pain for a long time, the cause of disease, the pathological knowledge that comprise migraine, rheumatic arthritis, osteoarthritis, backache, cancerous pain and neuropathic pain are still very shallow, therefore, especially the treatment of neuropathic pain is still very difficult for the pain that most of disease is caused.Though the effort through more than 30 years does not all obtain satisfied the solution, its basic reason is that the etiology of pain and pharmacological understanding are made slow progress.At present the most frequently used analgesic be the non-steroidal anti-inflammatory medicine (be called for short: NSAIDs) and opiates, conventional NSAID s has 18 kinds, among studying nearly more than 100 kinds.Though their clinical efficacy is better, untoward reaction is bound to arouse fear, as gastrointestinal reaction, gastric ulcer, gastrorrhagia and the allergy etc. of NSAIDs.Opiates then limits the use of because of its addiction in accordance with the law.Particularly to nociceptive pain (nociceptive pain), complexity local pain syndrome (complex regional pain syndrome, be called for short: CRPS) and wound, inflammation or other diseases etc. cause that the neuropathic pain treatment difficulty due to nerve injury or the pathological changes is bigger, potent opioid analgesics also is difficult to prove effective.The good news is, recent years, etiology and the pharmacological understanding to chronic pain had breakthrough, make pathology, physiology and the therapeutic notion of chronic pain that fundamental shifts take place, break away from the out-moded convention of traditional NSAIDs and opioid drug, developed a collection of novel analgesics.But major part is in development or the clinical trial.In addition, external scholar is a target with N type voltage-sensitive calcium channel, trk C, Adenosine kinase, P material receptor and cannabinol receptor in recent years, also doing a lot of work aspect the medicine of exploitation neuropathic pain, seeking treatment neuropathic pain analgesics has become advanced subject clinical and basis and medicine research.
(6) pharmacology activity research of phenolic acid compound progress
1, antiplatelet aggregation and prevent that seven water soluble ingredients that thrombosis gives the quiet notes Radix Salviae Miltiorrhizae of rat from showing that salvianolic acid A and salvianolic acid B have stronger inhibitory action to collagen-induced platelet aggregation, its IC to the result of study of rat platelet aggregation
50Be respectively 0.32mmol/L and 0.26mmol/L, to the inductive gathering of ADP, then salvianolic acid A effectively and salvianolic acid B is invalid.Rosmarinic acid has the gentle thrombotic effect that prevents, it is one of effective ingredient of Radix Salviae Miltiorrhizae anti thrombotic action.Rosmarinic acid is 50mg/kg (iv), and 100mg/kg is 41% and 55.8% (P＜0.05) to the thrombotic suppression ratio of rat vein.
2, the microcirculation improvement obstacle is by observing mice mesentery arteriole external caliber, blood flow rate and the change situation of flow under different condition, show salvianolic acid A and salvianolic acid B topical to the effect of having clear improvement of epinephrine induced mice mesentery microcirculation disturbance, quiet notes salvianolic acid A also has same purpose.
3, (be called for short: MDA) inhibitory action of Sheng Chenging is all strong than vitamin E to the mouse liver even slurry malonaldehyde for anti peroxidation of lipid salvianolic acid A, salvianolic acid B, salvianolic acid C and rosmarinic acid, its inhibition strength is followed successively by salvianolic acid A＞salvianolic acid C＞salvianolic acid B＞rosmarinic acid, and four kinds of compositions are stronger 10～100 times than mannitol to the scavenging action of hydroxy radical.The mice that oral 50% ethanol 15ml/kg is caused acute alcoholism, (100mg/kg * 3, po) after the treatment, mouse liver MDA content significantly reduces with rosmarinic acid.Salvianolic acid A, salvianolic acid B and rosmarinic acid are to (being called for short: NADPH) or by Fe by vitamin C-nicotinamide-adenine dinucleotide phosphate
2+The rat brain that-cysteine brings out, liver, the MC lipid peroxidation of kidney all have very strong inhibitory action, and its effect power is followed successively by salvianolic acid A, salvianolic acid B, rosmarinic acid, and be stronger 100～1000 times than the support one's family effect of case E of antioxidant.Salvianolic acid A can suppress Fe
2+The forfeiture of the rat heart that-cysteine causes and the mitochondrial lipid peroxidation of liver and atpase activity suppresses mitochondrial swelling and the decline of liver mitochondrion membrane fluidity that lipid peroxidation causes.
4, the cardiac toxicity to the preventive effect amycin of amycin cardiac toxicity is because of it produces free radical at heart, due to the injury of myocardium mitochondrion.Salvianolic acid A can be removed the 0H that is produced by amycin, and the cardiac toxicity that Ah mould's index is risen has preventive effect, and the amycin antitumor action is not had influence.
5, the anti-gastric-ulcer salvianolic acid A has the Gaster Sus domestica of inhibition H
+-K
+The effect of/ATP enzyme and PNPP enzyme, IC
50Be respectively 5.2 * 10
-7With 1.7 * 10
-6Mol/L.Salvianolic acid A (25mg/kg, ip) rat tolerance secretion to pylorus ligation has very strong inhibitory action, and same dosage salvianolic acid A can weaken owing to water logging or the mandatory stomach damage that stress cause.These results show that salvianolic acid A is by suppressing stomach H
+-K
+/ ATP enzyme and have gastric acid inhibitory secretion and antiulcer activity.
6, the magnesium salt that alleviates uremic symptom salvianolic acid B can reduce owing to taking adenine and cause the concentration of urinary nitrogen in the uremic mouse blood, kreatinin, methyl amidine guanidine, guanidinosuccinic acid, thereby significantly alleviates mouse retention toxication shape.
7, suppress adenyl cyclase rosmarinic acid and alkannic acid and methyl ester thereof and all have stronger inhibitory action to the basic adenyl cyclase of Mus brain with the activatory adenyl cyclase of 5umol/L forskolin.
8, other are Radix Ginseng defying age main active as ginsenoside and some compound of phenolic acid; Tea polyphenols is the general name of multiple phenol derivatives, accounts for 25%, and it comprises catechin, anthocyanidin, flavone and flavonol, phenolic acid four compounds.They contain polyhydroxy, have the character of phenol, and significant pharmacological action is arranged, if can blood sugar lowering, blood fat, prevent atherosclerosis; Can with the protein bound of source of disease bacterium such as antibacterial such as escherichia coli in the human body, streptococcus and typhoid fever, cholera, make it precipitation, suppress the growth of antibacterial, impel the various bacteria loss of activity; Can also make harmful heavy metals such as noxious substance such as nicotine in the human body, apomorphine, quinine and lead, cobalt, silver, copper produce precipitation, weaken or eliminate hazardness.
By literature search etc., up to the present, still find no the report that active site or the active component of single Fructus Xanthii are followed the trail of screening, also do not see relevant report about the purposes aspect of Fructus Xanthii active site extract.
Summary of the invention
The technical problem that will solve required for the present invention is the new purposes that discloses the total extract of a kind of Chinese medicine Fructus Xanthii, to overcome the above-mentioned defective that prior art exists.
That is to say, the invention is intended to the active site of clear and definite Chinese medicine Fructus Xanthii and active component and preparation method thereof, and then the total extract of Fructus Xanthii is used to prepare the anti-inflammatory response product; Promptly the present invention relates to Chinese medicine Fructus Xanthii total glucosides extract and preparation method thereof, and this total glycosides extractive and the application in preparation anti-inflammatory response product such as compositions such as pharmaceutical composition thereof.
Described anti-inflammatory response product is meant the product that is used for antiinflammatory and associated conditions, the product of antiviral and associated conditions, the product of analgesia and associated conditions, diagnosis, detect, the product of treatment or research acute and chronic rhinitis and associated conditions, or diagnosis, detect, the product of treatment or research sinusitis and associated conditions; Wherein, described anti-inflammatory response product is to comprise in anti-inflammatory response medicine, anti-inflammatory response reagent, anti-inflammatory response food or the anti-inflammatory response beverage etc. one or more, preferably anti-inflammatory reaction medicine.
(1) technical conceive
The independent development original new drug is a present urgent task of China.China's Chinese medicine and pharmacy has a long history, and has also accumulated rich experience with Chinese herbal medicine prevention and treatment disease aspect, and therefore seeking effective active component from Chinese medicine is a valid approach, also is the place of the advantage of Chinese original new drug development.
The inventor has retrieved " newly organized national Chinese patent medicine ", " books such as clinical prescription handbook commonly used, " China's Chinese patent medicine complete works commonly used ", and department of eye patient's hospital administration and commercially available medicine carried out the investigation statistics analysis, discovery is in 30 kinds of conventional Chinese medicine prescriptions of treatment rhinitis, sinusitis, have 23 kinds that contain Fructus Xanthii, account for 76.7%, and all use, be nose section key medicine as monarch drug or ministerial drug.Therefore infer the material or the material group that in Fructus Xanthii, very likely have antiinflammatory, antibiotic, antiviral activity.But because to its chemical constitution study not deeply, the pharmacological screening deficiency causes active site and active component indeterminate and do not have feasible quality standard, has limited the further development and utilization of Fructus Xanthii.
Therefore, the present invention carries out the chemical constitution study of system by the total extract to single Fructus Xanthii medical material, and screens and prove the activity and the purposes of this total extract.
Through chemical constitution study, prove that the main component in the Fructus Xanthii active site is diterpene glycosides compound and phenolic acid compound.And according to literature search, the inventor finds that phenolic acid compound has the number of significant pharmacologically active mostly, as famous salvianolic acid, gingkolic acid or the like (the scape technology of passing away part), thereby the inventor infers anti-inflammatory and antalgic, the antiviral activity of Fructus Xanthii and treats the clinical drug effect of multiple cacorhinia, should mainly be to bring into play by the drug effect of active site Fructus Xanthii total glycosides, result of study also proves and has confirmed that Fructus Xanthii total glucosides extract has significant pharmacologically active.
(2) Fructus Xanthii total glucosides extract
1, the composition of Fructus Xanthii total glucosides extract
The inventor finds mainly to contain a large amount of volatile oil, sesquiterpene lactones and water solublity glycosides compound in the Fructus Xanthii by the Fructus Xanthii medical material being carried out the experimentatioies such as chemical constituent separation, purification and structure evaluation of system.
Composition in the Fructus Xanthii total glucosides extract mainly comprises two compounds such as diterpene glycosides compound and phenolic acid compound; Above-described two compounds are the main effective ingredient in the Fructus Xanthii total glucosides extract, also comprise other compositions.
Wherein, the content range of diterpene glycosides compound in this total glycosides extractive is 0.5%～99% (W/W, i.e. percentage by weight), preferred 5.0%～95.0%;
Wherein, the content range of phenolic acid compound in this total glycosides extractive is 0.5%～99% (W/W), preferred 5.0%～95.0%.
Wherein, the content range of other compositions in this total glycosides extractive is below 0.5%, and other compositions are to comprise in tannin, monosaccharide or polysaccharide, xanthene ketone (xanthones) or the carotenoid etc. one or more.
Existing studies show that, other compositions do not have negative influence at least to the aspects such as use of drug effect or medicine, and it is higher to separate these composition costs, therefore the necessity that is not further purified at present.
2, the chemical structure of general formula of the diterpene glycosides compound in the Fructus Xanthii is as follows:
Wherein, R
1A kind of in hydrogen, methyl or the carboxyl; R
2, R
3A kind of in hydrogen, sulfonic group, acetyl group, propiono or the dimethyl propylene acyl group.
Table 1 has been listed in the structural formula of part diterpene glycosides compound and R
1, R
2, R
3The corresponding relation of group:
Work as R
1=COOH, R
2=R
3During=H, expression diterpene glycosides compound A;
Work as R
1=COOH, R
2=H, R
3=COCH
2CH (CH
3)
2The time, expression diterpene glycosides compound B;
Work as R
1=COOH, R
2=SO
3 -, R
3=COCH
2CH (CH
3)
2The time, expression diterpene glycosides compound C;
Work as R
1=H, R
2=H, R
3=COCH
2CH (CH
3)
2The time, expression diterpene glycosides compound D;
Work as R
1=H, R
2=SO
3 -, R
3=COCH
2CH (CH
3)
2The time, expression diterpene glycosides compound E.
Several diterpene glycosides compound chemical structural formulas in table 1, the Fructus Xanthii
| R 1 | R 2 | R 3 | |
| A | COOH | H | H |
| B | COOH | H | -COCH 2CH(CH 3) 2 |
| C | COOH | SO 3 - | -COCH 2CH(CH 3) 2 |
| D | H | H | -COCH 2CH(CH 3) 2 |
| E | H | SO 3 - | -COCH 2CH(CH 3) 2 |
3, the chemical structure of general formula of the phenolic acid compound in the Fructus Xanthii is as follows:
Wherein, R
1A kind of in hydrogen or the alkali metal; R
2, R
3And R
4A kind of in hydrogen or the coffee acyl.Coffee acyl is Caffeoyl, and structure is as follows:
Table 2 has been listed in the structural formula of part phenolic acid compound and R
1, R
2, R
3The corresponding relation of group.
Work as R
1=H, R
2=R
3=R
4During=Caffeoyl, expression phenolic acid compound A;
Work as R
1=R
3=H, R
2=R
4During=Caffeoyl, expression phenolic acid compound B;
Work as R
1=R
2=H, R
3=R
4During=Caffeoyl, expression phenolic acid compound C;
Work as R
1=K, R
2=R
4=H, R
3During=Caffeoyl, expression phenolic acid compound D.
The chemical structural formula of several phenolic acid compounds in table 2, the Fructus Xanthii
| R 1 | R 2 | R 3 | R 4 | |
| A | H | Caffeoyl | Caffeoyl | Caffeoyl |
| B | H | Caffeoyl | H | Caffeoyl |
| C | H | H | Caffeoyl | Caffeoyl |
| D | K | H | Caffeoyl | H |
(3) preparation method of Fructus Xanthii total glucosides extract
The preparation method of the said Fructus Xanthii total glucosides extract of the present invention comprises the steps:
(1) extract: it is some to get the Fructus Xanthii raw material, extracts, and gets extracting solution, i.e. Fructus Xanthii total extract;
(2) separation and purification:, promptly get Fructus Xanthii total glucosides extract with the extracting solution separation and purification.
Described extracting method comprises all operable methods well known in the art such as solvent extraction method.
The extracting method of solvent extraction method mentioned above is the conventional extracting method of this area, that is to say to comprise ultrasonic extraction commonly used, dipping extraction method, percolation extraction method, decoct in extraction method, heating and refluxing extraction method or the continuous backflow extraction method etc. one or more; Extraction time can be once or repeatedly.Simultaneously, factors such as the degree of grinding of raw material, extraction time, extraction temperature, appointed condition also can both influence extraction efficiency, must take in.Various extracting method comprise all technical data of ins and outs, all can be referring to relevant teaching material and relevant technical literature etc.
The routine that the employed extraction solvent of solvent extraction method mentioned above is this area is extracted solvent, that is to say one or more of extraction such as three classes that comprise common water reagent, hydrophilic organic solvent or lipophilic organic solvent solvent;
Described water reagent is to comprise a kind of in water, sour water or the aqueous alkali etc.;
Described hydrophilic organic solvent is general said and the miscible organic solvent of water, comprise in ethanol, ethanol water or the methanol etc. one or more, in preferred alcohol or the Different concentrations of alcohol aqueous solution etc. one or more, further preferred Different concentrations of alcohol aqueous solution;
Described lipophilic organic solvent is the organic solvent that generally said and water can not be miscible, comprise in petroleum ether, chloroform, ether, ethyl acetate, dichloromethane or the dichloroethanes etc. one or more, in preferred petroleum ether, chloroform, ether, ethyl acetate, dichloromethane or the dichloroethanes etc. one or more, one or more in further preferred chloroform, ether, ethyl acetate or the dichloromethane etc.
The resulting Fructus Xanthii total extract of said extracted method needs further separation and purification.
Described isolation and purification method is all operable methods well known in the art, comprise solvent segregation, solvent extraction (comprise in extraction, counter current continuous extraction method, counter-current distribution method or the drop counter-current distribution method etc. one or more), the macroporous adsorbent resin method, the sedimentation method, salting out method, one or more in column chromatography or crystallization and recrystallization and the Steppecd crystallization etc.; These methods all are known technologies of this area, at needs further in the conclusive evidence, are easy to find all technical data that comprise ins and outs from relevant teaching material and relevant technical literature etc.
In order to make product property stable, easy to use and preserve, and the bioavailability that improves product, also can increase the step of an optimization, i.e. step 3:
(3) drying.
Described drying means is an operable method well known in the art, comprises that atmosphere pressure desiccation is as in oven for drying, hypobaric drying method, boulton process, spray drying method, freeze-drying, far infrared heating drying method or micro-wave drying method etc. one or more.
In the specific implementation, need adopt wherein suitable method, and choose measures necessary such as appropriate condition to reach the set goal according to existing fund, technology and relevant requirement.And these methods also all are known technologies of this area, at needs further in the conclusive evidence, all are to be easy to find all technical data that comprise ins and outs from relevant teaching material and relevant technical literature etc.
(4) purposes of Fructus Xanthii total glucosides extract
1, general introduction
Further purpose of the present invention provides the new purposes in preparation anti-inflammatory response product of Fructus Xanthii total glucosides extract, and product is to comprise in medicine, reagent, the Foods or drinks etc. one or more, preferred agents.
By pharmacologically active screening proof, the Fructus Xanthii total glucosides extract that adopts n-butanol extraction position or macroporous adsorbent resin 5～75% ethanol elution positions to obtain is the active site of its antiinflammatory, analgesia, antiviral or diagnosis, detection, treatment and research cacorhinia and associated conditions.Completed acute toxicity testing proves, the mouse stomach administration surpasses 2.0g/kg to the maximum tolerated dose of this active site, be equivalent to 440 times of clinical recommended drug dosage, show that this effective site is safe and reliable, solved complicated component in the Chinese medicine compound, active constituent content is low and has contained the problem of toxic component.
The inventor finds that Fructus Xanthii total glucosides extract has antiinflammatory action and analgesic activity, can significantly reduce inflammation swelling degree, suppress capillary permeability, and have antivirus action.
Simultaneously, the inventor finds that Fructus Xanthii total glucosides extract can alleviate the rhinitis cellular infiltration due to rhinitis, the sinusitis, eliminate the nasal mucosa edema, thereby connective tissue proliferation can improve nasal mucosa swelling and ventilatory function under the inhibition mucosa, reduce nose and secrete thing, thereby inflammation is disappeared, and effect is better than clinical medicine BIYUANSHU KOUFUYE commonly used etc.
2, the using method of Fructus Xanthii total glucosides extract and compositions thereof and requirement
Fructus Xanthii total glucosides extract of the present invention can be united use separately or with other active component, comprises being used to prepare the product that is used to diagnose, detect, treat or study relevant disease, comprises medicine, reagent, Foods or drinks etc., especially medicine.
Aspect concrete use, Fructus Xanthii total glucosides extract of the present invention can use separately, can also use with other many chemical substances.These chemical substances biologically active or have the function of treatment disease whether no matter, comprise miscellaneous function as collaborative amplification, antagonism or alleviate the side effect etc. of Fructus Xanthii total glucosides extract, these chemical substances are to comprise in pharmaceutically acceptable carrier, food, natural product, chemical synthetic drug or the human medication etc. one or more; Preferably include in pharmaceutically acceptable carrier or the food etc. one or more; Further preferred pharmaceutically acceptable carrier.
" pharmaceutically acceptable carrier " used herein comprises one or more in any He all physiology suitable solvent, disperse medium, afterbirth, antibacterial and antifungal, isotonic agent or the absorption delay agent etc.The example of pharmaceutically acceptable carrier comprises one or more in one or more water, saline, phosphate-buffered saline, glucose, glycerol or ethanol or the like and the compositions thereof.In many cases, in said composition, preferably include isotonic agent, for example, sugar, such as in the polyhydric alcohol of mannitol, sorbitol, sorbitol or the sodium chloride etc. one or more.Pharmaceutically acceptable carrier can also comprise a spot of auxiliary substance, one or more in wetting agent or emulsifying agent, antiseptic or the buffer etc. for example, and they have strengthened the effect duration or the effectiveness of this Fructus Xanthii total glucosides extract.
From concrete classification, said pharmaceutically acceptable carrier is meant the pharmaceutical carrier of medicine and pharmacology field routine, comprises excipient, as in starch or the water etc. one or more; Lubricant is as in glycerol or the magnesium stearate etc. one or more; Disintegrating agent is as microcrystalline Cellulose etc.; Filler is as in starch or the lactose etc. one or more; Bonding agent is as in pregelatinized Starch, dextrin, cellulose derivative, alginate, gelatin or the polyvinylpyrrolidone etc. one or more; Osmotic pressure regulator is as in glucose, sucrose, sorbitol or the mannitol etc. one or more; Diluent is as water etc.; Disintegrating agent is as in agar, calcium carbonate or the sodium bicarbonate etc. one or more; Absorption enhancer is as quaternary ammonium compound etc.; Surfactant is as hexadecanol etc.; Absorption carrier is as in Kaolin or the soap clay etc. one or more; Lubricant is as in Pulvis Talci, calcium stearate, magnesium stearate or the Polyethylene Glycol etc. one or more; In addition, can also in compositions, add other adjuvant, as in flavouring agent or the sweeting agent etc. one or more.
For example, the active component Fructus Xanthii total glucosides extract is dissolved, suspendible or (for example be emulsifiable in the suitable aqueous solvent, distilled water, in normal saline or the Green's solution etc. one or more) or in the oil-based solvent (for example, vegetable oil is olive oil for example, Oleum sesami, Oleum Gossypii semen, in Semen Maydis oil or the propylene glycol etc. one or more) in, can make ejection preparation, wherein (for example can contain dispersant in the solvent, polyoxyethylene sorbitan monoleate, polyoxyethylene hardened castor oil 60, Polyethylene Glycol, benzyl alcohol, in chlorobutanol or the phenol etc. one or more), osmotic pressure regulator (for example, sodium chloride, glycerol, the D9-mannose, in D-sorbitol or the glucose etc. one or more).In this case, if necessary, can add additive, for example solubilizing agent (for example, one or more in sodium salicylate or the sodium acetate etc.), stabilizing agent (for example, human serum albumin etc.), analgesic (for example, benzyl alcohol etc.) etc.
Of the present invention and Fructus Xanthii total glucosides extract can also unite use with the form of compositions, particularly with other chemical substance such as medicine animal especially mammal is comprised that people or other animals treat compositions for use or similar compositions.Described mammal comprises in people, mice, rat, sheep, monkey, cattle, pig, horse, rabbit, dog, chimpanzee, baboon, Adeps seu carnis Rhiopithecus roxellanae, macaque or the Rhesus Macacus etc. one or more.For example, Fructus Xanthii total glucosides extract of the present invention can be added be suitable for to curee's Pharmaceutical composition in.Usually, this Pharmaceutical composition comprises Fructus Xanthii total glucosides extract of the present invention and pharmaceutically acceptable carrier.
The compositions of Fructus Xanthii total glucosides extract particularly pharmaceutical composition can have various forms, comprises in the dosage forms such as liquid, semisolid and solid for example one or more; Wherein said pharmaceutical composition comprises that the Fructus Xanthii total glucosides extract for the treatment of effective dose is an active component, and one or more pharmaceutically acceptable carriers.
The pharmaceutical composition of Fructus Xanthii total glucosides extract can adopt conventional production method well known in the art to make various dosage forms, and active component is mixed with one or more carriers, is made into required dosage form then.Described dosage form comprises one or more in tablet, capsule, granule, suspensoid, Emulsion, solution, syrup or the injection etc., takes one or more route of administration in oral or injection (comprise in intravenous injection, intravenous drip, intramuscular injection or the subcutaneous injection etc. one or more), the mucosa dialysis etc. to carry out diagnosis, detection, treatment or the scientific research of antiinflammatory, antiviral, analgesia and acute and chronic rhinitis, sinusitis and associated conditions.
It is 0.5%～99% active component Fructus Xanthii total glucosides extract that pharmaceutical composition preferably contains weight ratio, further preferably contain weight ratio and be 1%～95% active component Fructus Xanthii total glucosides extract, most preferably contain weight ratio and be 5%～90% active component Fructus Xanthii total glucosides extract.
The pharmaceutical composition of Fructus Xanthii total glucosides extract generally must be aseptic and stable under the production condition of storage.Said composition can be mixed with solution, microemulsion, dispersion liquid, liposome or other is suitable for the ordered structure of high drug level.By with a kind of of this Fructus Xanthii total glucosides extract of aequum and required mentioned component or combine to add in the appropriate solvent and then carry out aseptic filtration and prepare aseptic parenteral solution.Generally speaking, prepare dispersion liquid by this Fructus Xanthii total glucosides extract being added in the aseptic solvent that contains basic disperse medium and required above-mentioned other composition.Under the situation of the sterile powder that is used to prepare aseptic parenteral solution, the preparation method of recommendation is vacuum drying and lyophilized preparation.For example, by passing through to keep required granular size such as the coating of lecithin, under the situation of dispersion liquid and, can keeping the adequate liquidity of solution by using surfactant.By comprising that in said composition the medicament (for example Monostearate or gelatin) that postpones to absorb can reach the prolongation absorption of injectable composition.
When being used for the patient, Fructus Xanthii total glucosides extract dosage of the present invention is 5～20mg/kgd, and this dosage or consumption decide according to the age of patient or user and the situation of body weight and health or patient's symptom usually.
Fructus Xanthii total glucosides extract of the present invention and Pharmaceutical composition thereof can comprise the Fructus Xanthii total glucosides extract of the present invention of " treatment effective dose " or " prevention effective dose "." treatment effective dose " is meant at the dosage of necessity and effectively reaches the amount of required therapeutic effect under the time.The treatment effective dose of Fructus Xanthii total glucosides extract can cause that at this individuality the factors such as ability of required reaction change according to the patient's condition, age, sex and body weight and this Fructus Xanthii total glucosides extract such as individuality.The treatment effective dose also refers to that the useful therapeutic effect of this Fructus Xanthii total glucosides extract surpasses the amount of its any toxicity or harmful effect." prevention effective dose " is meant the amount that effectively reaches required preventive effect under necessary dosage and time.Because preventive dose is used for the ill preceding or early stage curee of disease, the prevention effective dose is usually less than the treatment effective dose.The typical non-limiting scope of the treatment of Fructus Xanthii total glucosides extract of the present invention or prevention effective dose is 5～20mg/kg, more preferably 5～10mg/kg.Should note, dose value will change according to disease type of desiring to alleviate and seriousness, that is to say when being used for the patient that the dosage of Fructus Xanthii total glucosides extract of the present invention or consumption decide according to the age of patient or user and the situation of body weight and health or patient's symptom usually.In addition; should understand; for any specific curee; should along with the time according to individual need and give with or supervision give with the people's of described compositions professional judgement and adjust the given dose system; and the dosage range that this paper sets only be illustrative, the scope or the practice of the compositions of can't requirement for restriction protecting.
That is to say, need be according to object, route of administration, institute's disease of treat and the situation etc. of treatment, variation Fructus Xanthii total glucosides extract of the present invention at every turn and/or dosage or the consumption of every day.For example, give mammal through vein, adult (as body weight 60kg) especially, the single dose of described Fructus Xanthii total glucosides extract is about 5～10mg, preferably about 10mg, preferred administration every day 1～3 time.Can adjust dosage unit, to propose the best required reaction of arch (for example treatment or prevention are replied).For example, can single heavy dose of administration can give several divided doses or reduce or increase dosage in proportion according to the urgency of treatment situation in a period of time.The non-intestinal compositions that preparation is easy to the unified dosage unit form of administration and dosage is especially favourable.Dosage unit form used herein refers to be suitable for the physical separation unit of dosage unit of the mammalian subject of desire treatment; The calculating that each unit contains scheduled volume is used for together producing with required pharmaceutical carrier the active matter Fructus Xanthii total glucosides extract of required therapeutic effect.The specification of dosage unit form of the present invention, determine and directly depend on the specific characteristic of following (a) this Fructus Xanthii total glucosides extract and the particular treatment of desiring to reach or preventive effect and (b) interior in mixing this technology that is used for the treatment of the individual sensitivity Fructus Xanthii total glucosides extract by following in restriction.
3, the pharmaceutical dosage form of Fructus Xanthii total glucosides extract and compositions thereof and route of administration
Fructus Xanthii total glucosides extract of the present invention and preparation of compositions anti-inflammatory response product thereof wherein can antiinflammatory, antiviral, analgesia and diagnosis, detection, treatments according to the product of the requirement of beverage, food technology field preparation or study acute and chronic rhinitis, sinusitis and associated conditions thereof; Can be used in patient's treatment or health care according to the product of the requirement of medical technical field preparation, can either be directly used in the medicine of preparation treatment or health care separately, also can mix with many chemical substances or make up, directly or indirectly be used to prepare the medicine of treatment or health care.Chemical substance described here is above described identical with this section.
In the present invention, required material comprises raw material of the present invention, above-mentioned matching used chemical substance etc., all should adopt the material of food stage or pharmaceutical grade according to practical situation and needs.
Fructus Xanthii total glucosides extract of the present invention and compositions thereof can be with the whole bag of tricks administration known in the art, although route of administration/administering mode of recommending in many therapeutic use is spray or oral administration.But the technical staff will appreciate that route of administration/administering mode changes with required result.In some concrete enforcement, the carrier that this reactive compound can avoid rapid release with this chemical compound of protection is preparation example such as empty release formulation together, comprises that graft transmission system, transdermal paste one or more in transmission system or the microcapsule transmission system etc.In addition, can also use biodegradable, biocompatible polymer, for example one or more in ethylene-ethyl acetate, polyanhydride, polyglycolic acid, collagen protein, polyorthoesters or the polylactic acid etc.Prepare the equal patent applied for of many methods of this preparation or generally known to those skilled in the art (referring to for example Sustained and Controlled Release Drug Delivery Systems, J.R.Robinson edits, Marcel Dekker, Inc., New York, 1978).
Fructus Xanthii total glucosides extract of the present invention and compositions thereof, usually by oral, snuffing is gone into, one or more modes in rectum or the parenteral etc., is applied to the patient who needs this treatment.
Be used for when oral, can be made into conventional solid preparation such as in tablet, powder, granule or the capsule etc. one or more.When implementing, Fructus Xanthii total glucosides extract of the present invention can be together oral with for example inert diluent or assimilable edible carrier.This Fructus Xanthii total glucosides extract (with its composition altogether, if desired) can also be wrapped in hard or soft shell gelatin capsules, is pressed into tablet or directly adds in curee's the meals.About oral therapeutic administration, described Fructus Xanthii total glucosides extract can be added with excipient and use with one or more forms in edible tablet, buccal tablet agent, tincture, capsule, suspension, syrup or wafer or the like.
For to give Fructus Xanthii total glucosides extract of the present invention outside the parenterai administration, may need with preventing that the material of its inactivation from together giving to this Fructus Xanthii total glucosides extract coating or with this Fructus Xanthii total glucosides extract.The reactive compound that replenishes can also be added in the said composition.In the specific implementation, Fructus Xanthii total glucosides extract of the present invention and one or more other medicines that can be used for the treatment of disease are prepared altogether and/or given altogether.Thisly unite use, can utilize this medicine that gives primely, therefore avoid possible toxicity or the complication relevant with various monotherapies than low dosage.
Make in liquid preparation such as water preparation, oil-suspending agent or other liquid preparation one or more, as in syrup or the elixir etc. one or more; When being used for parenteral, can be made in solution, water preparation or the oiliness suspending agent etc. of injection one or more.
In the above-described type of service, preferred form is one or more in tablet, coated tablet, capsule, suppository, nasal spray, nasal drop or the injection etc., in further preferred nasal spray, nasal drop or the tablet etc. one or more, preferred especially nasal spray.
In addition, the employed medicinal raw material of Fructus Xanthii total glucosides extract also can be directly used in preparation anti-inflammatory response product in some cases separately, also can mix with many chemical substances or make up, directly or indirectly be used to prepare the anti-inflammatory response product with the form of compositions.Chemical substance described here is above described identical with this section.
For example, the powder of the employed medicinal raw material of Fructus Xanthii total glucosides extract is used to prepare the particularly various dosage forms of medicine of anti-inflammatory response product, or the powder of the employed medicinal raw material of Fructus Xanthii total glucosides extract is used to prepare the especially various dosage forms of medicine of anti-inflammatory response product with relevant adjuvant, or the powder of the employed medicinal raw material of Fructus Xanthii total glucosides extract and relevant preparation anti-inflammatory response product such as medicine one are used from the various dosage forms of preparation anti-inflammatory response product such as medicine, or the powder of the employed medicinal raw material of Fructus Xanthii total glucosides extract and relevant ancillary drug one are used from the various dosage forms of preparation anti-inflammatory response product such as medicine, as tablet, capsule, in granule or the suspensoid etc. one or more, preferred capsule.
One of described method is that the powder fill with the employed medicinal raw material of Fructus Xanthii total glucosides extract is a capsule, two of method is to be capsule with the powder of the employed medicinal raw material of Fructus Xanthii total glucosides extract and relevant preparation anti-inflammatory response product such as medicine fill together, and three of method is to be capsule with the powder of the employed medicinal raw material of Fructus Xanthii total glucosides extract with relevant ancillary drug fill together; Four of method is the powder of the employed medicinal raw material of Fructus Xanthii total glucosides extract directly to be pressed together according to a conventional method with relevant adjuvant be tablet or granule, five of method is the powder of the employed medicinal raw material of Fructus Xanthii total glucosides extract, relevant preparation anti-inflammatory response product such as medicine directly to be pressed according to a conventional method with relevant adjuvant together be that tablet or granule, six of method are the powder of the employed medicinal raw material of Fructus Xanthii total glucosides extract, relevant ancillary drug directly to be pressed according to a conventional method with relevant adjuvant together be tablet or granule etc.
Except that six kinds of above-mentioned basic skills, can also select other forms of the employed medicinal raw material of Fructus Xanthii total glucosides extract or the employed medicinal raw material of Fructus Xanthii total glucosides extract is carried out after method well known in the art handles, prepare the product that contains the employed medicinal raw material of Fructus Xanthii total glucosides extract such as the medicine of various dosage forms.But, it should be noted that, in the employed medicinal raw material of above-mentioned direct use Fructus Xanthii total glucosides extract, should be earlier according to the dosage requirement of employed Fructus Xanthii total glucosides extract, conversion obtains the consumption of the employed medicinal raw material of Fructus Xanthii total glucosides extract of required use.
In sum, Fructus Xanthii total glucosides extract of the present invention and compositions thereof can be used for preparing the anti-inflammatory response product, preferred agents and food, further preferred agents.
(5) technology speciality
The present invention studies Fructus Xanthii total glucosides extract targetedly, and this raw material is safe in utilization, takes into account each other, one-object-many-purposes has been brought into play effect to greatest extent, and the scope of application is wide especially, therefore apply easily, can have a tremendous social and economic benefits in the short period of time.
That is to say, result of study of the present invention can further deeply be developed as have a potential applicability in clinical practice prevent and treat especially new drug of rhinitis, sinusitis, anti-inflammatory and antalgic and anti-virus product.This product has the advantage that determined curative effect, effective dose are low, have no side effect, and domestic with China, international like product is compared has significant advantage.Acute and chronic sinusitis is common clinical, frequently-occurring disease, the deterioration of the serious day by day and environment that pollutes along with global atmosphere, and the sickness rate of respiratory system diseases such as expectation sinusitis will constantly rise.Therefore, the present invention also can be follow-up new drug research and lays a good foundation, and further produces bigger economic benefit and social benefit.
Through secular pharmacology test, Fructus Xanthii total glucosides extract has antiinflammatory, antiviral, analgesia and treats activity acute and chronic rhinitis, sinusitis and associated conditions thereof, directly use Fructus Xanthii total glucosides extract, need not be through the metabolism of gastrointestinal tract antibacterial, make effect more direct, avoid that gastrointestinal bacterial flora between the individuality is active variantly to be caused the difference of metabolite and produce difference on the drug effect, thereby overcome the unmanageable problem of Chinese medicine dosage, and improved bioavailability.
Fructus Xanthii total glucosides extract pharmacological action of the present invention is stronger, and its raw material sources are abundant, and preparation technology is simple, the yield height.
Fructus Xanthii total glucosides extract also is the activity form in the gastrointestinal tract biotransformation, directly uses Fructus Xanthii total glucosides extract, and the bioavailability of medicament height can accurately be controlled dosage.The Fructus Xanthii total glucosides extract stable in properties uses the quality of the pharmaceutical preparations of Fructus Xanthii total glucosides extract preparation stable.
In addition, the Fructus Xanthii total glucosides extract chemical property is stable, antiinflammatory, antiviral, analgesia and to treat effect acute and chronic rhinitis, sinusitis and associated conditions thereof obvious are so it is more suitable for antiinflammatory, antiviral, analgesia and treats suitability for industrialized production acute and chronic rhinitis, sinusitis and associated conditions medicine thereof.
In a word, active adaption of the present invention the job demand of modern medical service, food, beverage and scientific research field and the needs of human nature service, be the safe raw material that is used to prepare the anti-inflammatory response product, directly or indirectly antiinflammatory, antiviral, analgesia and diagnosis, detection, treatment or study acute and chronic rhinitis, sinusitis and associated conditions thereof.
The specific embodiment
The present invention has studied the purposes of Fructus Xanthii total glucosides extract, a kind of particularly raw material of medicine of preparation anti-inflammatory response product such as medicine etc. or anti-inflammatory response product that can be used in is provided, be convenient to the safe handling in medical industry and fields such as relevant industries such as food, beverage, comprise diagnosis, detection, treatment or the scientific research etc. of disease.
Be example with the solvent extraction method below, elaborate the concrete operation method of preparation Fructus Xanthii total glucosides extract.
(1) extraction: it is some to get the Fructus Xanthii medical material, adds the extraction solvent and mixes, and extracts, and with extracting liquid filtering, concentrated, promptly gets Fructus Xanthii medical material total extract.
(2) separation and purification: Fructus Xanthii medical material total extract through purification procedures, is obtained Fructus Xanthii total glucosides extract.
Here said extraction, isolation and purification method comprise solvent extraction method as indicated above, solvent extraction or extraction well known in the art, isolation and purification methods such as macroporous adsorbent resin method, column chromatography.Specifically:
In step 1:
1. in the solvent extraction method that is adopted, extracting solvent is to comprise water, in alcohols or other organic solvents etc. one or more, described alcohols extracts solvent and comprises methanol, ethanol, ethanol water, in propanol or the butanols etc. one or more, described other organic solvents comprise ethyl acetate, acetone etc., preferred water, methanol, ethanol, ethanol water, propanol, butanols, ethyl acetate, in acetone and other organic solvent or its mixed solvent one or more, further preferably include a kind of in ethanol or the ethanol water etc., preferred especially 60%～90% ethanol water.
2. in the solvent extraction method that is adopted, one or more in the preferred ultrasonic extraction of extracting method, percolation extraction method or the heating and refluxing extraction method etc., further preferred heating and refluxing extraction method; Extraction time can be one or many.
3. with the extracting solution filtration under diminished pressure, concentrate Fructus Xanthii medical material total extract, the yield of Fructus Xanthii medical material total extract is 5.0%～20%, promptly Fructus Xanthii medical material total extract accounts for 5.0%～20% of Fructus Xanthii medical material gross weight.
In step 2:
1. the isolation and purification method preferred solvent extraction that is adopted is about to the aqueous dispersion of Fructus Xanthii medical material total extract, behind defat with petroleum ether, adopts suitable organic solvent extraction with the weeding of grease soluble components again, obtains extraction leftover; Or directly extract with the weeding of grease soluble components with suitable organic solvent, obtain extraction leftover; Described suitable organic solvent can select for use in chloroform, dichloromethane, ether or the ethyl acetate etc. one or more to extract; Extraction times can be one or many.
2. in the solvent extraction that is adopted, also need extraction leftover, continue to adopt n-butanol extraction gained behind the extraction liposoluble constituent, divide and get n-butanol layer, after adding anhydrous sodium sulfate dehydration, the concentrating under reduced pressure n-butanol portion promptly gets Fructus Xanthii total glucosides extract.At this moment, the yield of Fructus Xanthii total glucosides extract is 1%～10%, and promptly Fructus Xanthii total glucosides extract accounts for 1%～10% of Fructus Xanthii medical material gross weight.
3. the isolation and purification method that is adopted also can adopt the macroporous adsorbent resin method.The macroporous adsorbent resin method that is adopted, can be with Fructus Xanthii medical material total glycosides extractive reclaim under reduced pressure to there not being the alcohol flavor, filter to get filtrate, filtrate is transferred to relative density 1.0～1.1 with distilled water, last macroporous adsorptive resins, wash the solubility impurity that anhydrates with water, continue and carry out eluting, collect 5～75% ethanol elution positions, promptly get the eluent that is rich in phenolic acids and diterpene glycosides compound with eluting solvent such as Different concentrations of alcohol aqueous solution, reclaim under reduced pressure promptly gets Fructus Xanthii total glucosides extract to doing.At this moment, the yield of Fructus Xanthii total glucosides extract is 0.5%～10%, and promptly Fructus Xanthii total glucosides extract accounts for 0.5%～10% of Fructus Xanthii medical material gross weight.Preferred eluting solvent is that concentration is 40% ethanol water.
4. the macroporous adsorbent resin preparation method thereof of Fructus Xanthii total glucosides extract, can adopt the macroporous adsorbent resin of multiple model, comprise in the nonpolar and low pole resin such as D101, D520, D4006, H103, AB-8, Dianion HP 20 or XAD-7 one or more, also can be other can replace above-mentioned resin on performance filler, among preferred AB-8, D101 or the D520 etc. one or more, preferred especially AB-8.
Generally speaking, in the preparation method of Fructus Xanthii total glucosides extract, be to be raw material based on fresh medical material of Fructus Xanthii or commercially available medical material; After the raw material pulverizing, adopt in solvent extraction method, solvent extraction or the macroporous adsorbent resin method etc. one or more in turn, promptly get the crude product of Fructus Xanthii total glucosides extract; If in conjunction with in the conventional drying method such as concentrating under reduced pressure drying, spray drying, lyophilization one or more, then can prepare the extractum or the dry thing of Fructus Xanthii total glucosides extract crude product.
If further adopt column chromatography etc. to separate purification process, then can access phenolic acid compound in the Fructus Xanthii total glucosides extract and diterpene glycosides compound etc.; At this moment, phenolic acid compound that obtains and diterpene glycosides compound account for the content of Fructus Xanthii total glucosides extract 50%～100%, wherein, the diterpene glycosides compound accounts for 0.5%～99% (W/W) of Fructus Xanthii total glucosides extract content, and phenolic acid accounts for 0.5%～99% (W/W) of total glycosides extractive content.
Be example with several representative dosage forms below, elaborate the concrete preparation method of the various dosage forms of Fructus Xanthii total glucosides extract.
The present invention prepares injectable powder and generally adopts conventional freeze-drying, as solvent, the steps include: to get Fructus Xanthii total glucosides extract with water, adds excipient, is dissolved in water, and adds active carbon, filtration sterilization, and plug is partly rolled in fill, and lyophilization, tamponade are rolled lid and are got final product.Used excipient is selected from one or more in mannitol, gelatin hydrolysate, glucose, lactose or the dextran etc.Every bottle contains Fructus Xanthii total glucosides extract 10～100mg.
The present invention prepares injectable powder also can adopt spray drying method, as solvent, the steps include: to get Fructus Xanthii total glucosides extract with water, adds or do not add excipient (excipient is the same), be dissolved in water, add active carbon, filtration sterilization, spray drying, aseptic subpackaged, tamponade is rolled lid and is got final product.Every bottle contains Fructus Xanthii total glucosides extract 10～100mg.
When the present invention prepared small-volume injection, preparation got final product as solvent with water for injection, also can add appropriate amount of auxiliary materials, and adjuvant is selected from one or more in ethanol, propylene glycol, glycerol, Polyethylene Glycol, benzyl benzoate or the dimethyl acetylamide etc.Every contains Fructus Xanthii total glucosides extract 10～100mg.
The present invention prepares glucose infusion liquid or sodium chloride transfusion, with water for injection as solvent, add the preparation of an amount of glucose or sodium chloride and get final product, also can add appropriate amount of auxiliary materials, adjuvant is selected from one or more in ethanol, propylene glycol, glycerol, Polyethylene Glycol, benzyl benzoate or the dimethyl acetylamide etc.Every bottle contains Fructus Xanthii total glucosides extract 10～100mg.
The present invention prepares oral formulations such as tablet, capsule, granule, oral liquid, and adjuvant can be lactose, starch, dextrin, stearate etc., technology preparation routinely.
In the present invention, the example of the above-described specific embodiment and the following stated all is in order to set forth the present invention better, is not to be used for limiting scope of invention.
Below by embodiment the present invention is described in detail.
The preparation method 1 of embodiment 1, Fructus Xanthii total glucosides extract
The dry medical material 2.5Kg of Fructus Xanthii, with 50 liters of reflux, extract, of 90% alcoholic solution 2 times, each 2 hours, merge extracted twice liquid, concentrating under reduced pressure obtains extractum 350g, after the dispersion of 2 premium on currency, divide three extraction defats with 6 liters of petroleum ether in turn, respectively with 6 liters of chloroforms, 6 liters of each three abstraction impurity removal matter of ethyl acetate; Extraction leftover divides three extractions with 6 liters of n-butyl alcohol, combining extraction liquid, and lyophilization gets Fructus Xanthii total glucosides extract 21g.
The preparation method 2 of embodiment 2, Fructus Xanthii total glucosides extract
The dry medical material 2.5Kg of Fructus Xanthii, with 50 liters of supersound extraction of 70% alcoholic solution 2 times, each 2 hours, merge extracted twice liquid, concentrating under reduced pressure obtains extractum 208g, after the dispersion of 2 premium on currency, divide three extraction defats with 6 liters of petroleum ether in turn, respectively with 6 liters of chloroforms, 6 liters of each three abstraction impurity removal matter of ethyl acetate; Extraction leftover divides three extractions with 6 liters of n-butyl alcohol, combining extraction liquid, and reclaim under reduced pressure gets Fructus Xanthii total glucosides extract 17g to doing.
The preparation method 3 of embodiment 3, Fructus Xanthii total glucosides extract
The dry medical material 2.5Kg of Fructus Xanthii, extract 2 times with 50 liters of percolation of 75% alcoholic solution, each 24 hours, merge extracted twice liquid, concentrating under reduced pressure obtains extractum 285g, after the dispersion of 2 premium on currency, divide three extraction defats with 6 liters of petroleum ether in turn, respectively with 6 liters of chloroforms, 6 liters of each three abstraction impurity removal matter of ethyl acetate; Extraction leftover divides three extractions with 6 liters of n-butyl alcohol, combining extraction liquid, and reclaim under reduced pressure gets Fructus Xanthii total glucosides extract 19g to doing.
The preparation method 4 of embodiment 4, Fructus Xanthii total glucosides extract
The dry medical material 2.5Kg of Fructus Xanthii, with 50 liters of reflux, extract, of 75% alcoholic solution 2 times, each 2 hours, merge extracted twice liquid, reclaim under reduced pressure filters to get filtrate to there not being the alcohol flavor, filtrate transfers to relative density 1.05 with distilled water, last D101 macroporous adsorptive resins washes the solubility impurity that anhydrates with water, continues and uses the different concentration ethanol eluting, collect 50% ethanol elution position, promptly get the eluent that is rich in phenolic acid glycoside and diterpene glycosides compound, reclaim under reduced pressure gets Fructus Xanthii total glucosides extract 15g to doing.
The preparation method 5 of embodiment 5, Fructus Xanthii total glucosides extract
The dry medical material 2.5Kg of Fructus Xanthii, with 50 liters of reflux, extract, of 75% alcoholic solution 2 times, each 2 hours, merge extracted twice liquid, reclaim under reduced pressure filters to get filtrate to there not being the alcohol flavor, filtrate transfers to relative density 1.05 with distilled water, last AB-8 macroporous adsorptive resins washes the solubility impurity that anhydrates with water, continues and uses the different concentration ethanol eluting, collect 50% ethanol elution position, promptly get the eluent that is rich in phenolic acid glycoside and diterpene glycosides compound, reclaim under reduced pressure gets Fructus Xanthii total glucosides extract 20g to doing.
The preparation of embodiment 6, Fructus Xanthii total glucosides extract nasal drop
Get the above-mentioned Fructus Xanthii total glucosides extract 45g that obtains, add Fel Sus domestica unguentum 20g, chlorphenamine maleate 0.5g, Sodium Houttuyfonate 8g, add 10 times of distilled water dilutings, elimination is not tolerant, bottling, and sterilization is sealed and is promptly got the Fructus Xanthii total glucosides extract nasal drop.
Embodiment 7, Fructus Xanthii total glucosides extract drip capsular preparation
Get the above-mentioned Fructus Xanthii total glucosides extract 40g that obtains, add Fel Sus domestica unguentum 15, chlorphenamine maleate 0.3g, Sodium Houttuyfonate 6g, adding filler, 0.5～10% disintegrating agent carboxymethyl base sodium cellulosate, hydroxypropyl celluloses such as 40%～60% starch, dextrin, carboxymethyl starch, calcium hydrogen phosphate makes granule and makes it dry, and add fluidizer magnesium stearate, differential silica gel, make it dry, in incapsulating then, obtain product, i.e. the Fructus Xanthii total glucosides extract capsule.
The preparation of embodiment 8, Fructus Xanthii total glucosides extract capsule
(1) prescription
Fructus Xanthii total glucosides extract 1000.0g
Microcrystalline Cellulose 1000g
Carboxymethyl starch sodium 140g
Dehydrated alcohol is an amount of
Pulvis Talci 80g
Make 10000 capsules altogether
(2) preparation technology gets in crude drug Fructus Xanthii total glucosides extract and the prescription other adjuvant respectively by above prescription and crosses 100 mesh sieves respectively, put 60 ℃ of oven dry, take by weighing recipe quantity Fructus Xanthii total glucosides extract and microcrystalline Cellulose, the carboxymethyl starch sodium equivalent method mix homogeneously that progressively increases, with an amount of dehydrated alcohol system soft material, 30 mesh sieves are granulated, 50～60 ℃ of dryings 2 hours with 30 mesh sieve granulate, add the Pulvis Talci and the carboxymethyl starch sodium mix homogeneously of recipe quantity.
The preparation of embodiment 9, Fructus Xanthii total glucosides extract injectable powder
Get Fructus Xanthii total glucosides extract 30g, add dextran 30g, add 500ml water for injection, stir and make its dissolving; Add the injection water to 2000ml, add the 3.0g needle-use activated carbon, fully stirred 30 minutes; Decarbonization filtering; With 0.22 μ m filtering with microporous membrane; Be filled in the aseptic cillin bottle, every bottle of 2ml partly rolls plug; Lyophilization, tamponade is rolled lid and is got final product again.
The preparation of embodiment 10, Fructus Xanthii total glucosides extract injectable powder
Get Fructus Xanthii total glucosides extract 60g, add 500ml water for injection, stir and make its dissolving; Add the injection water to 1000ml, add the 1g needle-use activated carbon, fully stirred 30 minutes; Decarbonization filtering; With 0.22 μ m filtering with microporous membrane; Lyophilization gets sterilized powder, is distributed into 1000 bottles.
The preparation of embodiment 11, Fructus Xanthii total glucosides extract injectable powder
Get Fructus Xanthii total glucosides extract 40g, add lactose 50g, add 100ml water for injection, stir and make its dissolving; Add the injection water to 1000ml, add the 1.5g needle-use activated carbon, fully stirred 30 minutes; Decarbonization filtering; With 0.22 μ m filtering with microporous membrane; Spray drying gets sterilized powder, is distributed into 1000 bottles.
The preparation of embodiment 12, Fructus Xanthii total glucosides extract injectable powder
(1) prescription
Injection Fructus Xanthii total glucosides extract semi-finished product 150g
Mannitol 400g
Water for injection adds to 10000ml
Make 10000 bottles altogether
(2) preparation technology
Take by weighing the recipe quantity Fructus Xanthii total glucosides extract by above prescription, join in an amount of water for injection, stir and make its dissolving; Add recipe quantity mannitol, stir and make dissolving fully, add to the full amount of water for injection; Add 0.1% needle-use activated carbon of amount of liquid, fully stirred 30 minutes; Decarbonization filtering; With 0.22 μ m filtering with microporous membrane; Plug is partly rolled in fill; Lyophilization, lid is rolled in tamponade.Make 9735 bottles altogether, yield rate is 97.35%.
The preparation of embodiment 13, Fructus Xanthii total glucosides extract small-volume injection
Get Fructus Xanthii total glucosides extract 5g, add 100ml water for injection, stir and make its dissolving; Add the injection water to 1000ml, with 0.22 μ m filtering with microporous membrane; The packing embedding, every bottle of 10ml, sterilization gets final product.
The preparation of embodiment 14, Fructus Xanthii total glucosides extract small-volume injection
Get Fructus Xanthii total glucosides extract 10g, add propylene glycol 30g, add 200ml water for injection, stir and make its dissolving; Add the injection water to 1000ml, add the 1.5g needle-use activated carbon, fully stirred 30 minutes; Decarbonization filtering; With 0.22 μ m filtering with microporous membrane; The packing embedding, every bottle of 5ml, sterilization gets final product.
The preparation of embodiment 15, Fructus Xanthii total glucosides extract glucose infusion liquid
Get Fructus Xanthii total glucosides extract 2g, add Polyethylene Glycol 10g, add glucose 500g, add 2000ml water for injection, stir and make its dissolving; Add the injection water to 5000ml; With 0.22 μ m filtering with microporous membrane; The packing embedding, every bottle of 100ml, sterilization gets final product.
The preparation of embodiment 16, Fructus Xanthii total glucosides extract glucose infusion liquid
Get Fructus Xanthii total glucosides extract 2g, add glucose 250g, add 1000ml water for injection, stir and make its dissolving; Add the injection water to 5000ml; With 0.22 μ m filtering with microporous membrane; The packing embedding, every bottle of 250ml, sterilization gets final product.
The preparation of embodiment 17, the transfusion of Fructus Xanthii total glucosides extract sodium chloride
Get Fructus Xanthii total glucosides extract 1g, add sodium chloride 90g, add 1000ml water for injection, stir and make its dissolving; Add the injection water to 10000ml; With 0.22 μ m filtering with microporous membrane; The packing embedding, every bottle of 250ml, sterilization gets final product.
The preparation of embodiment 18, Fructus Xanthii total glucosides extract tablet
Get Fructus Xanthii total glucosides extract 80g, microcrystalline Cellulose 80g, lactose 15g, pregelatinized Starch 60g sieve, and mix homogeneously with an amount of 10%PVP alcoholic solution system soft material, is granulated, and drying adds magnesium stearate 3g, granulate, and tabletting is made 1000.
The preparation of embodiment 19, Fructus Xanthii total glucosides extract tablet
(1) prescription
Fructus Xanthii total glucosides extract 1000.0g
Microcrystalline Cellulose 1170.0g
Pregelatinized Starch 690.0g
Lactose 125.0g
The 5%PVP dehydrated alcohol is an amount of
Magnesium stearate 15.0g
Make 10000 altogether
(2) preparation technology
Take by weighing the principal agent and the adjuvant of recipe quantity respectively by above prescription, progressively increase behind the method mix homogeneously according to making soft material, system granule under the formulation and technology item by equivalent, dry, processes such as granulate, the heavy back of sheet single punch tablet machine and 10.5mm shallow concave punch tabletting have been calculated, control nude film hardness 5～7kg makes 9698 in tablet altogether, and yield rate is 96.98%.Adopt lift-over nebulization coating, art for coating is as follows:
The preparation of coating solution: gastric solubleness thin film dress material: 85G61235 is provided by Shanghai Colorcon Coating Technology Co., Ltd
Art for coating: will treat that (hardness 5kg～7kg) puts into coating pan to the coating nude film, start agitating device and air blast heater, when treating that the nude film temperature rises to 40 ℃, last 1/3 place that begins to open spray gun alignment tab bed sprays into the coating solution coating, 38 ℃～42 ℃ of control strip bed tempertaures, gas pound pressure 6kg, the coating solution flow velocity is 50mL/min, coating membrane heavily account for coated tablet heavy 3%.
The analgesic activity of embodiment 20, Fructus Xanthii total glucosides extract
Getting the above-mentioned Fructus Xanthii total glucosides extract that obtains (is called for short: CE) in right amount, adopt acetic acid induced mice writhing response model, observe the analgesic activity of Fructus Xanthii total glycosides.
(1) experimental technique
Get 60 of 20 ± 2g mices, male and female half and half, random packet.Each group press dosage successive administration 3d in the table 6 respectively, and before the last administration 30min lumbar injection 0.7% glacial acetic acid solution (0.1ml/10g Mus), the interior mouse writhing number of times of observed and recorded 10min the results are shown in Table 3 behind the 5min.
(2) experimental result
Table 3 is the result show, each group of CE can significantly reduce acetic acid induced mice writhing response number of times, has analgesic activity.
The influence of table 3, CE Dichlorodiphenyl Acetate induced mice writhing response (X ± SD, n=10)
| Group | Dosage | Route of administration | Turn round the body number of times |
| The normal saline group | 2ml/kg | Ig | 21.2±11.0 |
| The aspirin group | 0.1g/kg | Ig | 8.5±6.6 ** |
| The CE group | 10g/kg | Ig | 8.0±5.3 ** |
| 5.0g/kg | Ig | 8.8±7.0 ** | |
| 2.5g/kg | Ig | 11.9±7.8 * |
Compare with the normal saline group,
*P＜0.05,
*P＜0.01
Embodiment 21, Fructus Xanthii total glucosides extract are to the therapeutical effect of experimental sinusitis
(be called for short: CE) in right amount, adopt rabbit experiment sinusitis model, om observation Fructus Xanthii total glycosides is to the influence of rabbit nasal mucosa tectology to get the above-mentioned Fructus Xanthii total glucosides extract that obtains.
(1) experimental technique
Choose about body weight 2.5kg 56 of healthy new zealand white rabbits, male and female half and half, random packet.First day, left side maxillary sinus Dou Kou was opened in general anesthesia, blocks one-sided Dou Kou, operation stitching with gelfoam.Overall process is undertaken by the sterile working.Inject 108 CFU/ml streptococcus pneumoniae suspension 0.5ml next day, the administration group is tied medicine 10d continuously by dosage in the table 1, after the last administration separation and Culture cell, draw materials, make section.Light microscopic is observed down following index: 1. nasal mucosa thickness, for ease of the location relatively, with eyepiece micrometer record every part of specimen mucosal protrusion summit to the thickness (comprising epithelial layer and lamina propria) of nasal septal cartilage place lateral margin as mucosal thickness; 2. body of gland number in the proper mucous membrane is as the criterion with the average of body of gland number under the bilateral mucosal protrusion; 3. mucous epithelium goblet cell number is as the criterion with the average of counting 5 high power field goblet cell sums at random; 4. lymphatic nodule number in the proper mucous membrane is the sum of lymphatic nodule in the section.
(2) experimental result
Observation analysis is respectively organized the nasal mucosa tectology and is changed, and the results are shown in Table 4.
Table 3, table 4 presentation of results, the middle and high dosage group of CE significantly alleviates the rhinitis cellular infiltration, eliminate the nasal mucosa edema, suppress connective tissue proliferation under the mucosa, alleviate the effect of glandular hyperplasia in nasal mucosa epithelial goblet cell and the proper mucous membrane, the every index of tectology totally is better than the levofloxacin group, and high dose group is better than the BIYUANSHU group.
Table 4, CE to the influence of rabbit nasal sinuses mucosal tissue morphological indexes (X ± SD, n=8)
| Group | Dosage | Route of administration | Mucosal thickness (m) | Glandular tube number (individual) under the mucosal protrusion | Mucous epithelium goblet cell (individual) | Lymphatic nodule number (individual) |
| Normal group | - | - | 0.185±0.036 | 7.71±1.50 | 5.38±1.69 | 2.00±0.82 |
| Model group | - | - | 0.402±0.120 | 17.86±1.95 | 14.00±2.83 | 7.29±3.86 |
| The levofloxacin group | 120mg/kg | ig | 0.388±0.083 | 12.58±2.63 * | 12.34±3.22 | 5.77±1.98 * |
| The BIYUANSHU group | 2ml/kg | ig | 0.257±0.060 ** | 10.44±1.29 * | 10.56±1.88 * | 4.26±0.95 * |
| The CE group | 10g/kg | ig | 0.230±0.035 ** | 8.71±1.75 ** | 6.88±1.64 ** | 3.14±0.57 ** |
| 5.0g/kg | ig | 0.260±0.087 ** | 8.85±2.06 ** | 7.02±1.59 ** | 3.45±1.08 * | |
| 2.5g/kg | ig | 0.343±0.108 | 10.08±2.46 * | 11.23±1.20 * | 4.54±0.80 * |
Compare with model group,
*P＜0.05,
*P＜0.01
Embodiment 22, Fructus Xanthii total glucosides extract influenza virus inhibitory action
(1) experimental technique
1. MDCK (Madin darby canin kidney) passage and influenza virus (first 1 influenza virus) are cultivated: press document (Guo Yuanji, Cheng Xiaowen; 1997) method is carried out.
2. cell toxicity test: sample is added 0.1mL/ hole in the cell plates that grown up to cell monolayer, and add cell maintenance medium, cultivate 72h, the observation of cell pathological changes in 37 ℃, 5%CO2 incubator to the 1mL/ hole.Establish the mdck cell contrast simultaneously.Experiment repeats 2 times.The result shows: sample does not produce non-specific cell pathological changes (CPE) to mdck cell.
3. sample resisiting influenza virus test: 96 hole mdck cell culture plate cultured cells, establish cell matched group, virus control group, positive controls and test group respectively.First 1 influenza virus is added virus control group and test group, 37 ℃ of absorption 2h, sucking-off virus.The variable concentrations sample is joined each test group respectively, and 37 ℃, 5%CO2 were cultivated 3 days, viewing test result, and calculate the 50% inhibition concentration (IC of different pharmaceutical to virus
50).
(2) experimental result (seeing: table 5)
Experimental result shows that Fructus Xanthii total glucosides extract has the obvious suppression effect to influenza virus.
Table 5, Fructus Xanthii total glucosides extract are to the inhibitory action of influenza virus
| Group | IC 50(mmol/L) |
| CE | 4.2 |
| Ribavirin | 3.9 |
Claims (34)
1. the application of the compositions of Fructus Xanthii total glucosides extract in preparation anti-inflammatory response product, described anti-inflammatory response product is meant the product that is used for antiinflammatory and associated conditions, the product of antiviral and associated conditions, the analgesia and the product of associated conditions, or diagnosis, detect, in the product of treatment or research sinusitis and associated conditions one or more.
2. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 1 is characterized in that, described anti-inflammatory response product is to comprise in medicine, reagent, the Foods or drinks one or more.
3. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 2 is characterized in that, described anti-inflammatory response product is the medicine of diagnosis, detection, treatment or research sinusitis and associated conditions.
4. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 1 is characterized in that, described this total glycosides extractive is the total extract that comprises diterpene glycosides compound, phenolic acid compound and other compositions.
5. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 4, it is characterized in that described diterpene glycosides compound, phenolic acid compound and the content range of other compositions in this total glycosides extractive be respectively 0.5%～99% (percentage by weight), below 0.5%～99% and 0.5%.
6. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 5 is characterized in that, described diterpene glycosides compound and the content range of phenolic acid compound in this total glycosides extractive are respectively 5%～95% and 5%～95%.
7. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 4 is characterized in that, the chemical structure of general formula of diterpene glycosides compound is as follows:
Wherein, R
1A kind of in hydrogen, methyl or the carboxyl; R
2, R
3A kind of in hydrogen, sulfonic group, acetyl group, propiono or the dimethyl propylene acyl group.
8. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 7 is characterized in that, described diterpene glycosides compound is to comprise in the following chemical compound one or more:
Work as R
1=COOH, R
2=R
3During=H, expression diterpene glycosides compound A;
Work as R
1=COOH, R
2=H, R
3=COCH
2CH (CH
3)
2The time, expression diterpene glycosides compound B;
Work as R
1=COOH, R
2=SO
3 -, R
3=COCH
2CH (CH
3)
2The time, expression diterpene glycosides compound C;
Work as R
1=H, R
2=H, R
3=COCH
2CH (CH
3)
2The time, expression diterpene glycosides compound D;
Work as R
1=H, R
2=SO
3 -, R
3=COCH
2CH (CH
3)
2The time, expression diterpene glycosides compound E.
9. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 4 is characterized in that, the chemical structure of general formula of described phenolic acid compound is as follows:
Wherein, R
1A kind of in hydrogen or the alkali metal; R
2, R
3And R
4A kind of in hydrogen or the coffee acyl.
10. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 9 is characterized in that, described phenolic acid compound is to comprise in the following chemical compound one or more:
Work as R
1=H, R
2=R
3=R
4During=coffee acyl, expression phenolic acid compound A;
Work as R
1=R
3=H, R
2=R
4During=coffee acyl, expression phenolic acid compound B;
Work as R
1=R
2=H, R
3=R
4During=coffee acyl, expression phenolic acid compound C;
Work as R
1=K, R
2=R
4=H, R
3During=coffee acyl, expression phenolic acid compound D.
11. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 4 is characterized in that, the preparation method of described Fructus Xanthii total glucosides extract comprises the steps:
(1) extract: it is some to get the Fructus Xanthii raw material, extracts, and gets extracting solution, i.e. Fructus Xanthii total extract;
(2) separation and purification:, promptly get Fructus Xanthii total glucosides extract with the extracting solution separation and purification.
12. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 11 is characterized in that, described extracting method is all the operable methods well known in the art that comprise solvent extraction method.
13. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 12 is characterized in that, described extracting method is a solvent extraction method.
14. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 13, it is characterized in that described solvent extraction method is to comprise ultrasonic extraction commonly used, dipping extraction method, percolation extraction method, decoct in extraction method, heating and refluxing extraction method or the continuous backflow extraction method one or more; Extraction time is an one or many.
15. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 14 is characterized in that, described solvent extraction method is to comprise a kind of in ultrasonic extraction, percolation extraction method or the heating and refluxing extraction method; Extraction time is repeatedly.
16. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 15, it is characterized in that the employed extraction solvent of described solvent extraction method is to comprise that common water reagent, hydrophilic organic solvent or lipophilic organic solvent three classes extract one or more in the solvent.
17. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 16 is characterized in that, described water reagent is to comprise a kind of in water, sour water or the aqueous alkali; Described hydrophilic organic solvent is to comprise in ethanol, ethanol water or the methanol one or more; Described lipophilic organic solvent is to comprise in petroleum ether, chloroform, ether, ethyl acetate, dichloromethane or the dichloroethanes one or more.
18. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 11 is characterized in that, described extracting method is: it is some to get the Fructus Xanthii medical material, add and extract solvent, extract,, promptly get Fructus Xanthii medical material total extract extracting liquid filtering, concentrated.
19. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 18 is characterized in that, described extraction solvent is to comprise in water, alcohols or other organic solvents one or more.
20. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 19, it is characterized in that, it is to comprise in methanol, ethanol, ethanol water, propanol or the butanols one or more that described alcohols extracts solvent, and described other organic solvents are to comprise in ethyl acetate or the acetone one or more.
21. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 20 is characterized in that, it is 60%～90% ethanol water that described alcohols extracts solvent.
22. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 11, it is characterized in that described isolation and purification method is to comprise in solvent segregation, solvent extraction, macroporous adsorbent resin method, the sedimentation method, salting out method, column chromatography or crystallization and recrystallization and the Steppecd crystallization one or more.
23. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 22 is characterized in that, described solvent extraction is to comprise in extraction, counter current continuous extraction method, counter-current distribution method or the drop counter-current distribution method one or more.
24. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 23 is characterized in that, the operating procedure of described solvent extraction is:
(1) with the aqueous dispersion of Fructus Xanthii medical material total extract, behind defat with petroleum ether, adopt suitable organic solvent extraction again with the weeding of grease soluble components, obtain extraction leftover; Extraction times can be an one or many.
(2) extraction leftover is continued to adopt n-butyl alcohol extract, divide and get n-butanol layer, behind the adding anhydrous sodium sulfate dehydration, the concentrating under reduced pressure n-butanol portion promptly gets Fructus Xanthii total glucosides extract.
25. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 23, it is characterized in that, the operation of described solvent extraction comprises the steps: directly with suitable organic solvent Fructus Xanthii medical material total extract to be extracted with the weeding of grease soluble components, obtains extraction leftover; Extraction times can be an one or many.
26. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 25 is characterized in that, described suitable organic solvent is to comprise in chloroform, dichloromethane, ether or the ethyl acetate one or more.
27. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 22 is characterized in that, the operation of described macroporous adsorbent resin method comprises the steps:
(1) Fructus Xanthii medical material total glycosides extractive reclaim under reduced pressure is not distinguished the flavor of to there being alcohol, filter to get filtrate;
(2) filtrate is transferred to relative density 1.0～1.1 with distilled water, last macroporous adsorptive resins washes the solubility impurity that anhydrates with water;
(3) carry out eluting with eluting solvent, collect 5～75%7 pure eluting positions, promptly get the eluent that is rich in phenolic acids and diterpene glycosides compound;
(4) reclaim under reduced pressure promptly gets Fructus Xanthii total glucosides extract to doing.
28. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 27 is characterized in that, described eluting solvent is the Different concentrations of alcohol aqueous solution.
29. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 28 is characterized in that, described eluting solvent is that concentration is 40% ethanol water.
30. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 27 is characterized in that, described macroporous adsorbent resin is the macroporous adsorbent resin that comprises multiple model.
31. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 30 is characterized in that, described macroporous adsorbent resin is to comprise that non-polar resin, low pole resin or other can replace a kind of in the filler of above-mentioned resin on performance.
32. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 31, it is characterized in that described non-polar resin and low pole resin are to comprise a kind of among D101, D520, D4006, H103, AB-8, Dianion HP 20 or the XAD-7.
33. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 11 is characterized in that, also comprises exsiccant step.
34. the application of the compositions of Fructus Xanthii total glucosides extract according to claim 33, it is characterized in that described drying means is to comprise in atmosphere pressure desiccation, hypobaric drying method, boulton process, spray drying method, freeze-drying, far infrared heating drying method or the micro-wave drying method one or more.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100076867A CN1994352B (en) | 2005-03-28 | 2005-03-28 | Use of total glucosides extract of cocklebur fruit in preparation of product for resisting inflammatory reaction |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100076867A CN1994352B (en) | 2005-03-28 | 2005-03-28 | Use of total glucosides extract of cocklebur fruit in preparation of product for resisting inflammatory reaction |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2005100246939A Division CN100464760C (en) | 2005-03-28 | 2005-03-28 | Use of cocklebur fruit total glucoside extract in preparing anti inflammation reaction product |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1994352A true CN1994352A (en) | 2007-07-11 |
| CN1994352B CN1994352B (en) | 2010-11-10 |
Family
ID=38249608
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2007100076867A Expired - Fee Related CN1994352B (en) | 2005-03-28 | 2005-03-28 | Use of total glucosides extract of cocklebur fruit in preparation of product for resisting inflammatory reaction |
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| Country | Link |
|---|---|
| CN (1) | CN1994352B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108514568A (en) * | 2018-05-14 | 2018-09-11 | 黑龙江中医药大学 | The preparation method and its medical usage of thiazides compounds in the achene of Siberian cocklebur |
| CN109528796A (en) * | 2018-12-11 | 2019-03-29 | 江西赣隆药业有限公司 | A kind of Siberian cocklebur grass granule and preparation method thereof |
| CN110038023A (en) * | 2019-04-19 | 2019-07-23 | 温州医科大学 | A kind of pharmaceutical composition for the antiallergic activity substituting the achene of Siberian cocklebur |
| CN110585384A (en) * | 2019-10-11 | 2019-12-20 | 文莉 | Pharmaceutical composition for removing dampness and diminishing inflammation and preparation method and application thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1246008C (en) * | 2003-06-03 | 2006-03-22 | 广西亿康药业股份有限公司 | Chinese medicine preparation for curing acute and chronic rhinitis and its production method |
-
2005
- 2005-03-28 CN CN2007100076867A patent/CN1994352B/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108514568A (en) * | 2018-05-14 | 2018-09-11 | 黑龙江中医药大学 | The preparation method and its medical usage of thiazides compounds in the achene of Siberian cocklebur |
| CN109528796A (en) * | 2018-12-11 | 2019-03-29 | 江西赣隆药业有限公司 | A kind of Siberian cocklebur grass granule and preparation method thereof |
| CN110038023A (en) * | 2019-04-19 | 2019-07-23 | 温州医科大学 | A kind of pharmaceutical composition for the antiallergic activity substituting the achene of Siberian cocklebur |
| CN110038023B (en) * | 2019-04-19 | 2021-05-07 | 温州医科大学 | Anti-allergic pharmaceutical composition for replacing cocklebur fruit |
| CN110585384A (en) * | 2019-10-11 | 2019-12-20 | 文莉 | Pharmaceutical composition for removing dampness and diminishing inflammation and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1994352B (en) | 2010-11-10 |
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