CN103933100A - Preparation method of total alkaloid of Chinese mahonia stem and applications of total alkaloid of Chinese mahonia stem in preparation of drugs for preventing and treating gastric ulcer - Google Patents
Preparation method of total alkaloid of Chinese mahonia stem and applications of total alkaloid of Chinese mahonia stem in preparation of drugs for preventing and treating gastric ulcer Download PDFInfo
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Abstract
The invention relates to a method for extracting and purifying total alkaloid of Chinese mahonia stem; wherein the total alkaloid can be used to prevent and treat gastric ulcer, is mainly composed of berberine hydrochloride, jatrorrhizine hydrochloride, palmatine hydrochloride, and other alkaloids, and can be solely used or cooperatively used with pharmaceutically-acceptable carriers to prepare drugs for preventing and treating gastric ulcer.
Description
Technical field:
The present invention relates to the preparation of Caulis Mahoniae total alkaloids, and this total alkaloids and the application of pharmaceutical composition in prevention and treatment Gastric Ulcer Treatment thereof.
Background technology:
Gastric ulcer is one of a kind of common clinical, frequently-occurring disease, and complication is many, healing digestive system disease slow and that easily recur, and sickness rate is the trend rising year by year.Aspect epidemiology, peptic ulcer is a kind of commonly encountered diseases, and its sickness rate is at different times, and different regions difference is larger, and total sickness rate accounts for 10～20% of population.U.S. peptic ulcer patient approximately 10%, Germany is 12.3%; China is according to the investigation of minority area, and digestive tract disease sickness rate is 11.43%, and wherein peptic ulcer rate is 4.54%.The pathogenesis of gastric ulcer is comparatively complicated, illustrates not yet completely so far.At present, the clinical main medication of medicament for anti-gastric ulcer is: acid inhibitor, bisfentidine, proton pump inhibitor, pyloric spirobacterium inhibitor, gastric mucosa protective agent, medicine for stomach dynamic etc.Many drug combinations when clinical treatment gastric ulcer, along with increasing of medicament categories, digestive tract is lost infections cure rate and is greatly improved, and the medication cycle significantly shortens, and relapse rate obviously reduces, but drug combination expense is high, has certain side effect, and easily recurrence.Therefore,, for overcoming these shortcomings of Western medicine, be necessary to find the advantage effective ingredient in Chinese such as research has multicomponent, many target spots, toxic and side effects is little, the rear relapse rate of application is low, inexpensive.
Caulis Mahoniae is the dry stem of Berberidaceae plant Mahonia bealei (Fort.) Carr. Mahonia bealei (Fort.) Carr. or mahonia fortuneiFedde Mahonia fortunei (Lindl.) Fedde or south China Mahonia fortunei (Lindl.) Fedde Mahonia japonica (Thunb.) DC..It is cold in nature, and bitter in the mouth has heat clearing and damp drying, effect of eliminating fire and detoxication, the clinical damp-heat dysentery that is mainly used in, jaundice dark coloured urine, conjunctival congestion and swelling pain, toothache due to stomach-fire, the diseases such as furuncle carbuncle.Mahonia fortunei (Lindl.) Fedde platymiscium has multiple pharmacologically active: antibacterial, antiviral, antitumor, antiinflammatory, anti-increment activity, suppress the effects such as IL-8 generation, reversing multiple medicine resistance of tumor cells effect, blood vessel dilating and infection, free radical resisting and antioxidation.The multiple biological activitys such as the extract of Mahonia fortunei (Lindl.) Fedde platymiscium and chemical composition thereof have the lipoxidase of inhibition, suppress horn cell hypertrophy, remove oxygen-derived free radicals, anticomplementary, antibacterial and mutation.
Through retrieval, the rarely seen 74 sections of documents of the domestic research for Caulis Mahoniae at present, be mainly the mensuration of the content of extraction, the alkaloid (example hydrochloric acid berberine hydrochloric acid palmatine and Jatrorrhizine chloride) of the little ?alkali of chemical composition, single component to Caulis Mahoniae, the report of the reverse effect of Caulis Mahoniae extract to tumor, but there is not yet relevant report and patent for single Caulis Mahoniae, chemical composition and treatment and the preventive effect of effective site to gastric ulcer thereof wherein.
For find the active component for the treatment of gastric ulcer from Caulis Mahoniae, the present invention has carried out extraction purification to Caulis Mahoniae total alkaloids, obtain the total alkaloids effective site that purity is greater than 50%, this effective site is mainly berberine hydrochloride, palmatine hydrochloride, Jatrorrhizine chloride, and the activity research of total alkaloids is proved to it has the effect of prevention and treatment gastric ulcer.
Summary of the invention:
The technical problem that the present invention solves is to adopt water-soluble solvent to extract total alkaloids in Caulis Mahoniae, and is further purified acquisition Caulis Mahoniae total alkaloids, and studies the application of this total alkaloids in prevention and treatment Gastric Ulcer Treatment.
The technical problem that the present invention solves also comprises that Caulis Mahoniae total alkaloids can be for the preparation method of suitability for industrialized production, and the composition of Caulis Mahoniae total alkaloids, in view of the main chemical compositions of this total alkaloids explicit, this is by the quality control being conducive in suitability for industrialized production, thus the stability of guarantee curative effect and the quality of the pharmaceutical preparations.
Caulis Mahoniae total alkaloids of the present invention can be used as active constituents of medicine and is prepared into various clinical medicine preparations, wherein contains Caulis Mahoniae total alkaloids and the pharmaceutically acceptable carrier for the treatment of effective dose; Can also be the pharmaceutical composition of the common preparation of Caulis Mahoniae total alkaloids and other Chinese medicine or Chinese medicine extract or effective ingredient in Chinese or chemical composition or adjuvant, for prevention and treatment gastric ulcer.
For addressing the above problem, provide following technical scheme:
A Caulis Mahoniae total alkaloids for prevention and treatment gastric ulcer, mainly by Jatrorrhizine chloride, palmatine hydrochloride, N and related alkaloids form, by weight percentage, contain total alkaloids 30-99%.
Described total alkaloids, derive from Han little ?the alkaloidal medical material of bases, preferably Berberidaceae Mahonia bealei (Fort.) Carr. wood and leaf, mahonia fortuneiFedde wood and leaf, south China Gaulis Mahoniae and leaf.
The preparation method of described Caulis Mahoniae total alkaloids, comprises the following steps:
Method 1:
Medical material extracts under 50-100 DEG C of condition with water-soluble solvent, reclaim after solvent, again with 0.01-5% sulphuric acid solution extraction, alkali is adjusted pH value 7-14, leave standstill, filter, filtrate adds 5-30% sodium chloride, regulate pH value 1-7 with acid, filter, precipitation washing, 80 DEG C are dried to obtain dry extract, by this dry extract with water dissolution, again with 0.01-5% sulphuric acid solution extraction, alkali is adjusted pH value 7-14, leave standstill, filter, filtrate adds 5-30% sodium chloride, regulate PH1-7 with acid, filter, precipitation washing, 80 DEG C dry, obtain the total alkaloids that purity is greater than 30%, wherein said water-soluble solvent preferred water, a kind of solvent of ethanol or the mixed solvent of two kinds of solvent compositions, acid is hydrochloric acid or sulphuric acid preferably, the preferred ammonia of alkali or sodium hydroxide,
Method 2:
Medical material extracts under 50-100 DEG C of condition with water-soluble solvent, reclaim after solvent, again with 0.01-5% sulphuric acid solution extraction, alkali is adjusted pH value 7-14, leave standstill, filter, filtrate adds 5-30% sodium chloride, regulate pH value 1-7 with acid, filter, precipitation washing, 80 DEG C dry, obtain extractum, with water dissolution extractum, be splined on macroporous resin chromatographic column, first use distilled water remove impurity, again with water-soluble solvent eluting, reclaim eluent, dry, obtain the total alkaloids that purity is greater than 30%, wherein said water-soluble solvent preferred water, a kind of solvent of ethanol or the mixed solvent of two kinds of solvent compositions, acid is hydrochloric acid or sulphuric acid preferably, the preferred ammonia of alkali or sodium hydroxide, the preferred AB-8 of macroporous resin, D101, HPD100, HPD722, HPD700,
Method 3:
Medical material extracts under 50-100 DEG C of condition with water-soluble solvent, reclaim after solvent, again with 0.01-5% sulphuric acid solution extraction, alkali is adjusted pH value 7-14, leave standstill, filter, filtrate is adjusted pH value 1-7 with acid, be splined on cation exchange resin layer and analyse post, first use distilled water remove impurity, again with water-soluble solvent eluting, reclaim eluent, dry, obtain the total alkaloids that purity is greater than 30%, wherein said water-soluble solvent preferred water, a kind of solvent of ethanol or the mixed solvent of two kinds of solvent compositions, acid is hydrochloric acid or sulphuric acid preferably, the preferred ammonia of alkali or sodium hydroxide, the preferred D152 of cation exchange resin, D113, D151,
Method 4:
Medical material extracts under 50-100 DEG C of condition with water-soluble solvent, after reclaiming solvent, obtain concentrated solution, regulate pH value 1-7, be splined on chromatographic column, water remove impurity, acid water soluble solvent eluting, reclaim solvent and obtain extractum, extractum dissolves with water-soluble solvent again, be splined on chromatographic column, first use distilled water remove impurity, again with water-soluble solvent eluting, reclaim solvent, dry, obtain the total alkaloids that purity is greater than 30%, wherein said water-soluble solvent preferred water, a kind of solvent of ethanol or the mixed solvent of two kinds of solvent compositions, acid is hydrochloric acid or sulphuric acid preferably, the preferred ammonia of alkali or sodium hydroxide, the preferred macroporous resin of chromatographic column or cation exchange resin, the preferred AB-8 of macroporous resin, D101, HPD100, HPD722, HPD700, the preferred D152 of cation exchange resin, D113, D151.
The application of described Caulis Mahoniae total alkaloids in preparation prevention and treatment Gastric Ulcer Treatment.
A kind of Pharmaceutical composition, contains described Caulis Mahoniae total alkaloids, and contains pharmaceutically acceptable carrier.
Described Caulis Mahoniae total alkaloids or Pharmaceutical composition can be prepared into oral formulations, injection, suction preparation or external preparation.
For addressing the above problem, provide following technical scheme:
Detailed description of the invention:
The preparation of embodiment 1 Caulis Mahoniae total alkaloids
Take 100g broad-leaved Caulis Mahoniae powder, add 50% ethanol 1200ml, 90 DEG C of reflux, extract, filter, reclaim ethanol, to 200ml, again with 2% sulphuric acid reflux, extract, filter, regulate PH8-9, leave standstill, filter, obtain filtrate, add after 15% sodium chloride, regulate PH1-2, filter, precipitation washing, 80 DEG C dry, after this precipitation is dissolved with distilled water, again with 2% sulphuric acid reflux, extract, filtrate regulates PH8-9, leave standstill, filter, obtain filtrate, add after 15% sodium chloride, regulate PH1-2, filter, precipitation washing, 80 DEG C dry, obtaining purity is 52.12% (wherein Jatrorrhizine chloride, palmatine hydrochloride, the content of Jian is respectively 21.89%, 2.72%, 27.51%) total alkaloids.
The preparation of embodiment 2 Caulis Mahoniae total alkaloidss
Take 100g broad-leaved Caulis Mahoniae powder, add 50% ethanol 1200ml, 90 DEG C of reflux, extract, filter, reclaim ethanol, to 200ml, again with 2% sulphuric acid extraction, filter, regulate PH8-9, leave standstill, filter, obtain filtrate, add sodium chloride by 15%, stirring and dissolving, add hydrochloric acid, regulate PH1-2, filter, precipitation washing, 80 DEG C dry, obtain extractum, this extractum is dissolved in distilled water, get equal portions, go up respectively on D113 and HPD100 resin column, distilled water and 10% ethanol remove impurity, 50% acid alcohol eluting, obtaining purity is respectively 67.94% (wherein Jatrorrhizine chloride, palmatine hydrochloride, the content of Jian is respectively 40.11%, 16.58%, 11.26%) and 59.55% (wherein Jatrorrhizine chloride, palmatine hydrochloride, the content of Jian is respectively 31.22%, 17.13%, 11.20%) total alkaloids.
The preparation of embodiment 3 Caulis Mahoniae total alkaloidss
Take 150g broad-leaved Caulis Mahoniae powder, add 50% ethanol 1800ml, 90 DEG C of reflux, extract, filter, reclaim ethanol, to 300ml, again with 2% sulphuric acid solution extraction, filter, ammonia regulates PH8-9, leave standstill, filter, obtain filtrate, adjust PH1-2 with hydrochloric acid respectively, PH3-4, PH5-6, go up respectively on macroporous resin HPD100, first with distilled water remove impurity, again with 30% ethanol elution, it is 44.79% (wherein Jatrorrhizine chloride that recovery eluent obtains purity respectively, palmatine hydrochloride, the content of Jian is respectively 22.14%, 11.91%, 10.74%), 43.25% (wherein Jatrorrhizine chloride, palmatine hydrochloride, the content of Jian is respectively 21.54%, 11.94%, 10.22%), 43.90% (wherein Jatrorrhizine chloride, palmatine hydrochloride, the content of Jian is respectively 21.69%, 11.71%, 10.50%) total alkaloids.
The preparation of embodiment 4 Caulis Mahoniae total alkaloidss
Take 150g spire Caulis Mahoniae powder, add 50% ethanol 1800ml, 90 DEG C of reflux, extract, filter, reclaim ethanol to being about 1500ml, regulating PH is 2, be splined on cation exchange resin D113 post, with distilled water, 10%, 30% ethanol remove impurity, then use 40% acidic ethanol eluting, reclaim acid ethanol solution, obtain extractum, extractum is dissolved in distilled water, be splined on macroporous resin HPD100, use distilled water remove impurity, 30% ethanol elution, it is 58.27% (wherein Jatrorrhizine chloride that recovery ethanol obtains purity, palmatine hydrochloride, the content of Jian is respectively 30.67%, 16.34%, 11.27%) total alkaloids.
The preparation of embodiment 5. Caulis Mahoniae total alkaloidss
Take 400g spire Caulis Mahoniae powder, add 50% ethanol 4800ml, at 90 DEG C, extract, reclaim ethanol, regulating the PH of concentrated solution is 2, be splined on macroporous resin HPD100 resin column, use distilled water remove impurity, 30% ethanol elution, reclaim solvent, obtain extractum, this extractum is dissolved in distilled water, be splined on positive on exchanger resin D113 post, use successively distilled water, 10%, 30%, 50% ethanol remove impurity, then use 50% acid alcohol eluting, reclaim elute soln, dry that purity is 61.32% (wherein Jatrorrhizine chloride, palmatine hydrochloride, the content of Jian is respectively 28.07%, 17.48%, 15.77%) Caulis Mahoniae total alkaloids.
The preparation of embodiment 6. Caulis Mahoniae total alkaloidss
Take 150g Caulis Mahoniae powder, add 50% ethanol 1800ml, 90 DEG C of reflux, extract,, filter, reclaim ethanol to being about 1500ml, regulating PH is 2, be splined on the cation exchange resin D113 handling well, with distilled water, 10%, 30% ethanol remove impurity, then use 40-50% acidic ethanol eluting, reclaim acid ethanol solution, dry that purity purity is the Caulis Mahoniae total alkaloids of 52.87% (wherein Jatrorrhizine chloride, palmatine hydrochloride, N content are respectively 30.11%, 12.50%, 10.26%)
The preparation of embodiment 7. Caulis Mahoniae total alkaloidss
Take 45g broad-leaved Caulis Mahoniae leaf powder, add 50% ethanol 540ml, 90 DEG C of reflux, extract,, reclaim ethanol, and adjusting PH is 3-4, is splined on cation exchange resin D113 post.With distilled water and 10% ethanol remove impurity, then with 50% acid alcohol eluting, reclaim solvent, be drying to obtain purity and be 41.8% total alkaloids of (wherein Jatrorrhizine chloride, palmatine hydrochloride, the content of Jian are respectively 22.93%, 10.68%, 8.20%).
The preparation of embodiment 8. Caulis Mahoniae total alkaloidss
Take the narrow leaf Caulis Mahoniae of 45g powder, add 50% ethanol 540ml, reflux, extract, twice under 90 DEG C of conditions, reclaims ethanol, and adjusting PH is 3-4, is splined on cation exchange resin D151 post.With distilled water, 10%, 30% ethanol remove impurity, 50% acid alcohol eluting, reclaim acid alcohol, be drying to obtain purity and be 47.75% total alkaloids of (wherein Jatrorrhizine chloride, palmatine hydrochloride, the content of N are respectively 26.32%, 12.14%, 9.29%).
The preparation of embodiment 9. Caulis Mahoniae total alkaloidss
Take 45g south China Caulis Mahoniae powder, add 50% ethanol 540ml, 90 DEG C of reflux, extract,, reclaim ethanol, regulate PH as 3-4 taking hydrochloric acid, are splined on cation exchange resin D151 post.With distilled water, 10%, 30% ethanol remove impurity, 50% acid alcohol eluting, reclaim acid alcohol, be drying to obtain purity and be 52.69% total alkaloids of (wherein Jatrorrhizine chloride, palmatine hydrochloride, the content of N are respectively 28.73%, 13.44%, 10.52%).
The preparation of embodiment 10. Caulis Mahoniae total alkaloidss
Take 45g Caulis Mahoniae powder, add 50% ethanol 540ml, reflux, extract, twice under 90 DEG C of conditions, reclaims ethanol, and adjusting PH is 3-4, is splined on the D113 resin of handling well.With distilled water, 10%, 30%, 50% ethanol remove impurity, 50% acid alcohol eluting, reclaim acid alcohol, be dried to obtain extractum, dry extract is splined in HPD100 macroporous resin column after dissolving with 100ml distilled water, use distilled water remove impurity, 30% ethanol elution, reclaims eluent, and wherein Jatrorrhizine chloride, palmatine hydrochloride, the content of Jian are respectively 37.20%, 18.00%, 13.52% to be drying to obtain purity and to be 68.72%) total alkaloids.
Embodiment 11. impacts of Caulis Mahoniae total alkaloids on dehydrated alcohol type gastric ulcer
Adopt randomized that mice is divided into 7 groups, 10 every group, male and female half and half, are divided into dosage group, medicine high dose group in blank group, model group, omeprazole group, stomach-recovering capsule group, medicine low dose group, medicine.Every day gastric infusion 1 time, continuous 7 days, dehydrated alcohol (0.1mL/10g) gavage modeling after last administration 1h.Before modeling, water 24h is can't help in fasting.After induction 1h, de-cervical vertebra is put to death mice, operating scissors is opened mouse peritoneal and is found stomach, after ligation cardia, pylorus, get stomach respectively, inject 2% formalin 1ml to gastric, full stomach is placed in to the beaker that 2% formalin is housed and fixes 30min, cut off along greater gastric curvature, with normal saline flushing 3 times, use filter paper suck dry moisture, flatten, in order to the mensuration of ulcer index.Calculate ulcer inhibition rate (%)=(model group ulcer area-administration group ulcer area)
*100%/model group ulcer area
The impact of table 1 Caulis Mahoniae total alkaloids on dehydrated alcohol type gastric ulcer (
n=10)
| Group | Dosage (mg/kg) | Ulcer area (pixels2) | Suppression ratio (%) |
| Blank group | - | 0 | - |
| Model group | - | 10278.26±3313.09 | - |
| Omeprazole group | 6.067 | 2263.33±130.62 * | 77.98 |
| Stomach-recovering capsule group | 728 | 3255.00±484.91 * | 68.33 |
| Medicine low dose group | 12.5 | 6899.00±2167.17 | 32.88 |
| Dosage group in medicine | 37.5 | 3358.33±826.09 * | 67.33 |
| Medicine high dose group | 112.5 | 2718.00±397.89 * | 73.56 |
As can be seen from Table 1; the gastric ulcer that Caulis Mahoniae total alkaloids 12.5mg/kg, 37.5mg/kg, tri-dosage of 112.5mg/kg are induced dehydrated alcohol is all inhibited; suppression ratio is respectively 32.88%, 67.33% and 73.56%; wherein middle dosage and high dose have significant inhibitory action to mouse gastric ulcer, illustrate that contribution art total alkaloids has preventive effect to dehydrated alcohol type gastric ulcer.
Embodiment 12 impacts of Caulis Mahoniae total alkaloids on Pylorus Ligated Gastric Ulcer
Adopt randomized that rat is divided into 7 groups, 8 every group, male and female half and half, are divided into dosage group, medicine high dose group in blank group, model group, omeprazole group, stomach-recovering capsule group, medicine low dose group, medicine.Every day gastric infusion 1 time, continuous 7 days, after last administration 1h, the modeling of ligation pylorus, water 24h is can't help in fasting before modeling.10% chloral hydrate, by after rat anesthesia, is fixed on operation plate, cuts off belly wool, routine disinfection is opened an otch that is about 2cm along hunter's line under xiphoid-process, carefully mentions stomach, in pylorus and the ligation of duodenum joint portion, after ligation is good, send original place back to surgical thread, after sewing-up cut, sterilize, send back in cage, postoperative fasting is prohibited after water 6h, puts to death rat, open abdominal cavity, after ligation cardia, get stomach, collect gastric juice, centrifugal, measure gastric juice volume and gastric juice pH value.
The impact of table 2 Caulis Mahoniae total alkaloids on gastric acid (
n=8)
| Group | Dosage (mg/kg) | Gastric juice amount (ml) | Gastric juice pH value |
| Model | - | 10.34±0.79 | 2.29±0.71 |
| Omeprazole group | 6.067 | 3.54±0.59 ** | 4.15±0.49 * |
| Stomach-recovering capsule group | 728 | 7.30±0.92 * | 3.64±0.42 * |
| Medicine low dose group | 12.5 | 7.78±1.56 | 2.98±0.39 |
| Dosage group in medicine | 37.5 | 7.08±1.33 * | 3.80±0.61 * |
| Medicine high dose group | 112.5 | 4.57±0.62 ** | 4.02±0.33 * |
As shown in Table 2, high, the middle dosage of Caulis Mahoniae total alkaloids can significantly suppress pylorus ligation rat gastric secretion, rising gastric juice pH value, and prompting Caulis Mahoniae total alkaloids anti-ulcer effect may be relevant with gastric acid secretion inhibiting, rising gastric juice pH value.
Embodiment 13. impacts of Caulis Mahoniae total alkaloids on acetic acid type gastric ulcer
SD rat, male and female half and half, rat is opened abdominal cavity under narcotism, exposes stomach, the filter paper that is 5mm with diameter sticks 2 times at gastric antrum portion serosal surface, each 30s, covers nethike embrane after end of operation, sew up stomach wall, the each layer tissue of stomach wall, skin, adopt randomized that rat is divided into 7 groups, every group 8, male and female half and half, are divided into dosage group, medicine high dose group in blank group, model group, omeprazole group, stomach-recovering capsule group, medicine low dose group, medicine.Second day after operation starts gastric infusion, and giving animal conventional raising, successive administration 10 days, gets blood, put to death animal, take out stomach, inject 2% formalin 10ml to gastric, then stomach is soaked in to 30min in 2% formalin, to fix gastric skin, along greater gastric curvature, stomach is cut off, rinsed, flatten on glass plate.HE dyes and detects superoxide dismutase in serum (SOD), prostaglandin E
2(PGE
2) and epidermal growth factor (EGF).
The each group of table 3 rat blood serum SOD, PGE
2, EGF content detection value (
n=8)
| Group | Dosage (mg/kg) | SOD(u/ml) | PEG 2(ng/L) | EGF(ng/L) |
| Blank | - | 118±36 | 194±25 | 477±57 |
| Model | - | 57±18 | 82±20 | 577±106 |
| Omeprazole group | 6.067 | 108±16 * | 182±20 ** | 865±33 * |
| Stomach-recovering capsule group | 728 | 96±7 * | 159±43 * | 767±100 |
| Medicine low dose group | 12.5 | 66±19 | 122±37 | 718±154 |
| Dosage group in medicine | 37.5 | 97±8 * | 146±34 * | 831±65 * |
| Medicine high dose group | 112.5 | 101±39 * | 175±31 * | 847±45 * |
*p < 0.05, relatively has significant difference with model group
SOD (superoxide dismutase) is one of gastric mucosal protection factor; the height of its vigor has reflected the ability of body removing free radical indirectly; as can be seen from Table 3, omeprazole group, the middle and high dosage group of medicine can obviously improve Organism of Rats radical scavenging activity.
PGE
2(prostaglandin) has the gastric epithelial cells of promotion secretion mucus and bicarbonate; strengthen the effects such as mucosa blood circulation and protein synthesis; it is an important protection factor that strengthens mucosal epithelium cell turnover, maintains mucosal integrity; there is gastric acid secretion inhibiting and stimulate tissue repair to promote the effect of ulcer healing; as can be seen from Table 3; compared with model group, omeprazole group, the middle and high dosage group of medicine can obviously improve PGE in rat body
2content, promotes ulcer healing.
EGF (epidermal growth factor) is that one has gastric acid secretion inhibiting, promotes epithelial cell proliferation; the endogenous material of tissue repair and cytoprotection, avoids damage factor at protection gastric mucosa and destroys, maintains aspect gastrointestinal mucosa integrity and play very important effect.As can be seen from Table 3, compared with model group, in omeprazole group, medicine and high dose group can obviously improve EGF content in rat serum, promote ulcer healing.
In sum, Caulis Mahoniae total alkaloids may be by improving SOD in serum, PGE
2with EGF content, minimizing attack factor and the enhancing gastric mucosal protection factor realize, and are dosage correlation.
Claims (6)
1. prevention and a Caulis Mahoniae total alkaloids for the treatment of gastric ulcer, is characterized in that Caulis Mahoniae total alkaloids is mainly made up of Jatrorrhizine chloride, palmatine hydrochloride, Yan Suan little ?and related alkaloids, by weight percentage, contains total alkaloids 30-99%.
2. the total alkaloids described in claim 1, it is characterized in that deriving from Han little ?the alkaloidal medical material of bases, preferably Berberidaceae Mahonia bealei (Fort.) Carr. wood and leaf, mahonia fortuneiFedde wood and leaf, south China Gaulis Mahoniae and leaf.
3. the preparation method of Caulis Mahoniae total alkaloids claimed in claim 1, is characterized in that comprising the following steps:
Method 1:
Medical material extracts under 50-100 DEG C of condition with water-soluble solvent, reclaim after solvent, again with 0.01-5% sulphuric acid solution extraction, alkali is adjusted pH value 7-14, leave standstill, filter, filtrate adds 5-30% sodium chloride, regulate pH value 1-7 with acid, filter, precipitation washing, 80 DEG C are dried to obtain dry extract, by this dry extract with water dissolution, again with 0.01-5% sulphuric acid solution extraction, alkali is adjusted pH value 7-14, leave standstill, filter, filtrate adds 5-30% sodium chloride, regulate pH value 1-7 with acid, filter, precipitation washing, 80 DEG C dry, obtain the total alkaloids that purity is greater than 30%, wherein said water-soluble solvent preferred water, a kind of solvent of ethanol or the mixed solvent of two kinds of solvent compositions, acid is hydrochloric acid or sulphuric acid preferably, the preferred ammonia of alkali or sodium hydroxide,
Method 2:
Medical material extracts under 50-100 DEG C of condition with water-soluble solvent, reclaim after solvent, again with 0.01-5% sulphuric acid solution extraction, alkali is adjusted pH value 7-14, leave standstill, filter, filtrate adds 5-30% sodium chloride, regulate pH value 1-7 with acid, filter, precipitation washing, 80 DEG C dry, obtain extractum, with water dissolution extractum, be splined on macroporous resin chromatographic column, first use distilled water remove impurity, again with water-soluble solvent eluting, reclaim eluent, dry, obtain the total alkaloids that purity is greater than 30%, wherein said water-soluble solvent preferred water, a kind of solvent of ethanol or the mixed solvent of two kinds of solvent compositions, acid is hydrochloric acid or sulphuric acid preferably, the preferred ammonia of alkali or sodium hydroxide, the preferred AB-8 of macroporous resin, D101, HPD100, HPD722, HPD700,
Method 3:
Medical material extracts under 50-100 DEG C of condition with water-soluble solvent, reclaim after solvent, again with 0.01-5% sulphuric acid solution extraction, alkali is adjusted pH value 7-14, leave standstill, filter, filtrate is adjusted PH1-7 with acid, be splined on cation exchange resin layer and analyse post, first use distilled water remove impurity, again with water-soluble solvent eluting, reclaim eluent, dry, obtain the total alkaloids that purity is greater than 30%, wherein said water-soluble solvent preferred water, a kind of solvent of ethanol or the mixed solvent of two kinds of solvent compositions, acid is hydrochloric acid or sulphuric acid preferably, the preferred ammonia of alkali or sodium hydroxide, the preferred D152 of cation exchange resin, D113, D151,
Method 4:
Medical material extracts under 50-100 DEG C of condition with water-soluble solvent, after reclaiming solvent, obtain concentrated solution, regulate pH value 1-7, be splined on chromatographic column, water remove impurity, acid water soluble solvent eluting, reclaim solvent and obtain extractum, extractum dissolves with water-soluble solvent again, be splined on chromatographic column, first use distilled water remove impurity, again with water-soluble solvent eluting, reclaim solvent, dry, obtain the total alkaloids that purity is greater than 30%, wherein said water-soluble solvent preferred water, a kind of solvent of ethanol or the mixed solvent of two kinds of solvent compositions, acid is hydrochloric acid or sulphuric acid preferably, the preferred ammonia of alkali or sodium hydroxide, the preferred macroporous resin of chromatographic column or cation exchange resin, the wherein preferred AB-8 of macroporous resin, D101, HPD100, HPD722, HPD700, the preferred D152 of cation exchange resin, D113, D151.
4. the application of Caulis Mahoniae total alkaloids claimed in claim 1 in preparation prevention and treatment Gastric Ulcer Treatment.
5. a Pharmaceutical composition, is characterized in that containing Caulis Mahoniae total alkaloids described in claim 1, and contains pharmaceutically acceptable carrier.
6. the application in prevention and treatment Gastric Ulcer Treatment described in claim 1 and 4, is characterized in that described total alkaloids or Pharmaceutical composition can be prepared into oral formulations, injection, suction preparation or external preparation.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104610252A (en) * | 2015-01-07 | 2015-05-13 | 中国药科大学 | Extraction preparation method of palmatine chloride and application thereof to preparation of medicine for preventing and treating colorectal cancer |
| CN105693714A (en) * | 2016-03-09 | 2016-06-22 | 山东省分析测试中心 | Method for separating alkaloidal compounds from Chinese mahonia stems with pH-zone-refining countercurrent chromatography |
| CN107050177A (en) * | 2017-02-28 | 2017-08-18 | 吉林大学 | It is a kind of to be used to treat Chinese medicine composition of acne and preparation method thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104610252A (en) * | 2015-01-07 | 2015-05-13 | 中国药科大学 | Extraction preparation method of palmatine chloride and application thereof to preparation of medicine for preventing and treating colorectal cancer |
| CN105693714A (en) * | 2016-03-09 | 2016-06-22 | 山东省分析测试中心 | Method for separating alkaloidal compounds from Chinese mahonia stems with pH-zone-refining countercurrent chromatography |
| CN105693714B (en) * | 2016-03-09 | 2017-08-25 | 山东省分析测试中心 | The method of alkaloid compound in pH zone refining countercurrent separation leatherleaf mahonia |
| CN107050177A (en) * | 2017-02-28 | 2017-08-18 | 吉林大学 | It is a kind of to be used to treat Chinese medicine composition of acne and preparation method thereof |
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