CN105194608A - Micro-powder capsule for treating peptic ulcers - Google Patents
Micro-powder capsule for treating peptic ulcers Download PDFInfo
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Abstract
The invention discloses a micro-powder capsule for treating peptic ulcers. The micro-powder capsule is prepared by evenly mixing, by weight, 100 parts of drug particles with 1-5 parts of lubricants and encapsulating the mixture. The drug particles are prepared according to a method including: (1), weighing active pharmaceutical ingredients including, by weight, 7-13 parts of bighead atractylodes rhizomes, 7-13 parts of poria cocos, 7-13 parts of phaseolus calcaratus, 5-10 parts of astragalus membranaceus, 5-10 parts of capillary wormwood herbs, 5-10 parts of dandelion, 3-7 parts of bitter almonds, 3-7 parts of platycodon grandiflorum, 3-7 parts of pogostemon cablin, 2-3 parts of rhizoma zingiberis and 2-3 parts of ginseng; (2), smashing the active pharmaceutical ingredients until the particle size is 300-500 meshes, and evenly mixing the active pharmaceutical ingredients to obtain active pharmaceutical ingredient powder; (3), mixing the active pharmaceutical ingredient powder with dextrin according to the ratio of the active pharmaceutical ingredient powder to the dextrin being 100: (20-50)w/w, and performing wet granulation to obtain the drug particles. The micro-powder capsule has the advantages that the pharmaceutical composition plays a synergistic interaction role and can treat gastric ulcers, duodenal ulcers and erosive gastritis effectively after reasonable compatibility, and a new medication choice is provided for clinical peptic ulcer treatment.
Description
Technical field
The present invention relates to a kind of micro powder capsules agent for the treatment of peptic ulcer.
Background technology
Taste-blindness rate refers to the circular or oval full-thickness defects of the limitation of Grastiodudenal mucosa, and muscularis mucosae is penetrated, and inevitably leaves fibrous scar after healing, and surface is covered by one deck epithelium, and muscularis mucosae can not regenerate.It is because many reasons causes gastric acid, pepsin to be destroyed the self-digestion of gastric mucosa or gastric mucosal barrier that its cause of disease sums up.Think that the formation of ulcer and gastric Helicobacter pylori infection also have important relationship in recent years.
Chronic erosive gastritis, also known as gastritis verrucosa or varioliform gastritis generally rarely seen glutted, indigestion symptom such as pantothenic acid, belch, irregularities stomachache after meal.There is multiple excipuliform in Stomach in Patients mucosa, expands folded shape or pimple sample protuberance, diameter 5 ~ 10mm, the visible mucomembranous defect in top or umbilicus sample depression, and there is erosion at center, and protuberance is many without blush around, but the normal erythema similar with size, with gastric antrum, portion is common.
The medicine of the above-mentioned disease of Current therapeutic mostly is chemical drugs, and it is expensive, and side effect is large, and it is long to cure required time.Therefore, urgent need one is economical and practical, toxic and side effects is low, and the medicine of the above-mentioned disease of energy rapid healing.
And Chinese medicine in treatment of chronic diseases one to all playing an important role.Report, with Concha Arcae 75% and Radix Glycyrrhizae 25%, red in pulv, treatment gastric and duodenal ulcers, cure rate reaches 76% (" Chinese medicine voluminous dictionary " second edition, Shanghai science tech publishing house, in March, 2006,548th ~ 549 pages); Also people is had with Os Sepiae (life) 250g, Concha Arcae (calcined) 250g, Radix Et Rhizoma Rhei 200g, Radix Glycyrrhizae Preparata 200g, grinds to the powder, and boiled water is taken after mixing it with water after meal, each 15g, every day 3 ~ 4 times, be used for the treatment of peptic ulcer (Gu Linjiang, Cuttlefish Bone Powder for Peptic Ulcer, journal of shanghai Chinese medicine, phase calendar year 2001 9.Also there is people to treat peptic ulcer with Fructus Amomi Rotundus 10g, Rhizoma Atractylodis Macrocephalae 20g, Poria 20g, Herba Pogostemonis 15g, Herba Taraxaci 15g, Radix Ginseng 5g, Folium Perillae 10g, Semen Armeniacae Amarum 10g, Semen Coicis 20g, Herba Artemisiae Scopariae 15g, there is certain therapeutic effect.In Chinese patent 201110413686.3, provide the pharmaceutical composition of the good treatment peptic ulcer of a kind of drug activity, be prepared from by Semen Coicis 20 parts, Semen Benincasae 20 parts, Herba Artemisiae Scopariae 15 parts, the Rhizoma Atractylodis Macrocephalae 15 parts, Folium Perillae 10 parts, Semen Armeniacae Amarum 10 parts, Semen Lablab Album 10 parts, Semen Myristicae 10 parts, the Radix Astragali 10 parts, Radix Ginseng 5 parts, Fructus Forsythiae 5 parts.
Summary of the invention
The object of the present invention is to provide a kind of micro powder capsules agent for the treatment of peptic ulcer.
A kind of micro powder capsules agent for the treatment of peptic ulcer of the present invention, it is by drug particles 100 weight portion, lubricant 1 ~ 5 weight portion, after mixing, prepares in incapsulating; Wherein, drug particles prepares by the following method:
(1) by following weight proportion weighting raw materials:
Rhizoma Atractylodis Macrocephalae 7-13 part, Poria 7-13 part, Semen Phaseoli 7-13 part, Radix Astragali 5-10 part, Herba Artemisiae Scopariae 5-10 part, Herba Taraxaci 5-10 part, Semen Armeniacae Amarum 3-7 part, Radix Platycodonis 3-7 part, Herba Pogostemonis 3-7 part, Rhizoma Zingiberis 2-3 part, Radix Ginseng 2-3 part;
(2) crude drug being crushed to particle diameter is 300-500 order, after mixing, obtains raw material medicated powder;
(3) according to raw material medicated powder: dextrin=100:20 ~ 50w/w, add dextrin and raw material medicated powder mixes, wet granulation, obtain drug particles.
Further, crude drug weight proportion is as follows:
Rhizoma Atractylodis Macrocephalae 9-11 part, Poria 9-11 part, Semen Phaseoli 9-11 part, Radix Astragali 7-8 part, Herba Artemisiae Scopariae 7-8 part, Herba Taraxaci 7-8 part, Semen Armeniacae Amarum 4-6 part, Radix Platycodonis 4-6 part, Herba Pogostemonis 4-6 part, Rhizoma Zingiberis 2-3 part, Radix Ginseng 2-3 part.
Preferably, crude drug weight proportion is as follows:
The Rhizoma Atractylodis Macrocephalae 10 parts, 10 parts, Poria, Semen Phaseoli 10 parts, the Radix Astragali 7.5 parts, Herba Artemisiae Scopariae 7.5 parts, Herba Taraxaci 7.5 parts, Semen Armeniacae Amarum 5 parts, Radix Platycodonis 5 parts, Herba Pogostemonis 5 parts, Rhizoma Zingiberis 2.5 parts, Radix Ginseng 2.5 parts.
The present invention studies discovery, and when crude drug powder footpath is 400 order, the antiulcer activity of prescription is significantly better than other particle diameter groups, and the present invention preferably uses the raw material medicated powder of 400 order particle diameters to prepare drug particles and capsule.
Wherein, wet granulation adhesive therefor is selected from starch slurry, water or ethanol.
Further, described concentration of alcohol is 70%v/v.
Further, described lubricant is selected from magnesium stearate or Pulvis Talci.
Further, described lubricant quantity is 2 ~ 4 parts, is preferably 3 parts.
In the present invention, Poria is the dry sclerotia of On Polyporaceae Poria Poriacocos (Schw.) Wolf.Sweet, light, flat.GUIXIN, lung, spleen, kidney channel.Promoting diuresis to eliminate damp pathogen, spleen invigorating, mind calming.For edema oliguria, phlegm retention vertigo and palpitation, insufficiency of the spleen lack of appetite, have loose bowels in loose stool, irritability, palpitation with fear insomnia.
Semen Phaseoli is the dry mature seed of leguminous plant Semen Phaseoli VignaumbeuataOhwietOhashi or Semen Phaseoli VignaangularisohwietOhashi.Sweet, sour, flat.GUIXIN, small intestine meridian.Inducing diuresis to remove edema, removing toxic substances and promoting pus discharge.For edema distension, beriberi edema, jaundice dark coloured urine, beriberoid pyretic arthralgia, carbuncle sore tumefacting virus, abdominalgia with intestinal abscess.
Herba Taraxaci is Herba Taraxaci TaraxacummongolicumHand.Mazz, alkali ground Herba Taraxaci TaraxacumborealisinenseKitam. or belong to the dry herb of several plants together.Bitter, sweet, cold.Return liver, stomach warp.Heat-clearing and toxic substances removing, dispersing swelling and dissipating binds, inducing diuresis for treating stranguria syndrome.For furuncle swelling toxin, acute mastitis, scrofula, conjunctival congestion, pharyngalgia, lung abscess, acute appendicitis, jaundice due to damp-heat, the puckery pain of pyretic stranguria.
Herba Artemisiae Scopariae is that the quadrate part dryly of feverfew Artemisia scoparia Waldst. et Kit. ArtemisiascopariaWaldst.EtKit. or Herba Artemisiae Scopariae ArtemisiacapillariesThunb. divides.Bitter, pungent, be slightly cold, return spleen, stomach, liver, gallbladder meridian.Eliminating damp-heat, promoting the function of the gallbladder to alleviate jaundice.For jaundice oliguria, hygropyrexia heat-damp in summer, eczema pruritus.
The Rhizoma Atractylodis Macrocephalae is the dry rhizome of feverfew Rhizoma Atractylodis Macrocephalae AtractylodesmacrocephalaKoidz..Bitter, sweet, temperature, returns spleen, stomach warp.Invigorating the spleen and benefiting QI, dampness diuretic, hidroschesis, antiabortive.For insufficiency of the spleen lack of appetite, abdominal distention is had loose bowels, phlegm retention vertigo and palpitation, edema, spontaneous perspiration, frequent fetal movement.
Semen Armeniacae Amarum is the dry mature seed of rosaceous plant Prunus armeniaca L.var.ansu Maxim. PrunusarmeniacaL.var.ansuMaxim., Siberia Fructus Pruni PrunussibiricaL., prunus mandshuricaKoehne Prunusmandshurica (Maxim.) Koehne or Fructus Pruni PrunusarmeniacaL..Bitter, tepor, slightly poisonous, return lung, large intestine channel.Sending down the abnormal ascending QI relieving cough and asthma, loosening bowel to relieve constipation.For cough and asthma, fullness in the chest abundant expectoration, dryness of the intestine constipation.
The Radix Astragali is the dry root of leguminous plant Radix Astagali Astragalusmembranaceus (Fisch.) Bge.var.mongholicus (Bge.) Hsiao or Radix Astragali Astragalusmembranaceus (Fisch.) Bge..Sweet, tepor.Return lung, spleen channel.Tonifying Qi and lifting yang, strengthening superficial resistance to stop perspiration, inducing diuresis to remove edema, promotes the production of body fluid and nourishes blood, the stagnant blood stasis dispelling of row, detoxification evacuation of pus, expelling pus and promoting granulation.Weak in the deficiency of vital energy, anorexia and loose stool, sinking of QI of middle-JIAO, chronic diarrhea proctoptosis, metrorrhagia of having blood in stool, exterior deficiency spontaneous perspiration, deficiency of vital energy edema, interior-heat is quenched one's thirst, blood deficiency and yellow complexion, hemiplegia, and arthralgia pain is numb, and carbuncle difficulty is burst, and bursts for a long time and does not hold back.
Radix Platycodonis is the dry root of Campanulaceae Radix Platycodonis Platycodongrandiflorum (Jacq.) A.DC..Bitter, pungent, flat.Return lung meridian.Lung qi dispersing, sore-throat relieving, eliminates the phlegm, evacuation of pus.For cough with copious phlegm, uncomfortable in chest not smooth, pharyngalgia hoarseness, lung abscess vomiting pus.
Herba Pogostemonis is that the quadrate part dryly of labiate Herba Pogostemonis Pogostemoncablin (Blanco) Benth. divides.Pungent, tepor.Return spleen, stomach, lung meridian.Eliminating turbid pathogen with aromatics, and middle preventing or arresting vomiting, deliver expelling summer-heat.For turbid damp obstructing in middle-JIAO, gastral cavity painful abdominal mass is vomitted, heat-damp in summer exterior syndrome, hygropyrexia from the beginning of, heating asthenia, uncomfortable in chestly do not relax, cold-damp closes summer-heat, and stomachache is vomited and diarrhoea, nasosinusitis headache.
Rhizoma Zingiberis is the dry rhizome of zingiber ZingiberofficinaleRose..Pungent, heat.Return spleen, stomach, kidney, the heart, lung meridian.Warming spleen and stomach for dispelling cold, recuperating depleted YANG is promoted blood circulation, warming the lung to resolve fluid-retention.For coldness and pain in the epigastrium, vomiting is had loose bowels, and cold extremities faint pulse, cold fluid-retention is breathed with cough.
Radix Ginseng is the dry root welding technology of Araliaceae Radix Ginseng PanaxginsengC.A.Mey..Sweet, micro-hardship, tepor, return spleen, lung, the heart, kidney channel.Strongly invigorating primordial QI, multiple arteries and veins takes off admittedly, and invigorating the spleen to benefit the lung, promotes the production of body fluid and nourish blood, Fructus Alpiniae Oxyphyllae of calming the nerves.For weak body and prostration, cold extremities faint pulse, insufficiency of the spleen lack of appetite, the deficiency of the lung is breathed with cough, and Tianjin wound is thirsty, and interior-heat is quenched one's thirst, deficiency of qi and blood, prolonged illness weakness with emaciation, palpitation with fear insomnia, sexual impotence cold womb.
Pharmaceutical composition of the present invention is after reasonable compatibility, and pharmaceutical composition of the present invention has played synergistic function, can effectively treat gastric ulcer, duodenal ulcer and erosive gastritis, selects for clinical treatment peptic ulcer provides a kind of new medication.
Aforementioned pharmaceutical compositions has also been prepared into the medicated powder of specified particle diameter by the present invention, under this particle diameter condition, this medicated powder effectively can play the inhibit activities to ulcer equally, and this may be comparatively large with medicated powder specific surface area, and can being attached to skin surface better, to carry out directly treatment relevant.Meanwhile, the present invention also finds, when medicated powder particle diameter is 400 order, antiulcer activity is the strongest, is significantly better than other particle diameter conditions.
Find in the present invention's research, medicated powder specific surface area is excessive, easy moisture absorption, should not store and produce; And mobility is not good, be not easy to Production and Packaging; If be prepared into drug particles, need to add mixing in water for oral taking, mouthfeel is not good, and inconvenience is taken.In view of the foregoing, medicated powder is prepared into capsule by the present invention, is namely convenient to the storage of product, transport and packaging, is also convenient to patient simultaneously and uses.
Detailed description of the invention
The preparation of embodiment 1 pharmaceutical composition of the present invention
Rhizoma Atractylodis Macrocephalae 10g, Poria 10g, Semen Phaseoli 10g, Radix Astragali 7.5g, Herba Artemisiae Scopariae 7.5g, Herba Taraxaci 7.5g, Semen Armeniacae Amarum 5g, Radix Platycodonis 5g, Herba Pogostemonis 5g, Rhizoma Zingiberis 2.5g, Radix Ginseng 2.5g; After drying, be crushed to 400 orders, after mix homogeneously, obtain raw material medicated powder.
By raw material medicated powder: dextrin=100:20g/g, by raw material medicated powder and dextrin mix homogeneously, spray into 10%w/v starch slurry as binding agent, wet granulation, dry, obtain drug particles.
By drug particles: magnesium stearate=100:3g/g, drug particles and lubricant are mixed, encapsulated, obtain capsule of the present invention.
The preparation of embodiment 2 pharmaceutical composition of the present invention
Rhizoma Atractylodis Macrocephalae 180g, Poria 220g, Semen Phaseoli 220g, Radix Astragali 170g, Herba Artemisiae Scopariae 170g, Herba Taraxaci 170g, Semen Armeniacae Amarum 120g, Radix Platycodonis 120g, Herba Pogostemonis 120g, Rhizoma Zingiberis 60g, Radix Ginseng 60g; After drying, be crushed to 400 orders, after mix homogeneously, obtain raw material medicated powder.
By raw material medicated powder: dextrin=100:50g/g, by raw material medicated powder and dextrin mix homogeneously, using 70% ethanol as binding agent, wet granulation, dry, obtain drug particles.
By drug particles: magnesium stearate=100:4g/g, drug particles and lubricant are mixed, encapsulated, obtain capsule of the present invention.
The preparation of embodiment 3 pharmaceutical composition of the present invention
Rhizoma Atractylodis Macrocephalae 220g, Poria 180g, Semen Phaseoli 180g, Radix Astragali 130g, Herba Artemisiae Scopariae 130g, Herba Taraxaci 130g, Semen Armeniacae Amarum 80g, Radix Platycodonis 80g, Herba Pogostemonis 80g, Rhizoma Zingiberis 40g, Radix Ginseng 40g; After drying, be crushed to 350 orders, after mix homogeneously, obtain raw material medicated powder.
By raw material medicated powder: dextrin=100:30g/g, by raw material medicated powder and dextrin mix homogeneously, using water as binding agent, wet granulation, dry, obtain drug particles.
By drug particles: magnesium stearate=100:2g/g, drug particles and lubricant are mixed, encapsulated, obtain capsule of the present invention.
The preparation of embodiment 4 pharmaceutical composition of the present invention
Rhizoma Atractylodis Macrocephalae 260g, Poria 140g, Semen Phaseoli 140g, Radix Astragali 105g, Herba Artemisiae Scopariae 105g, Herba Taraxaci 105g, Semen Armeniacae Amarum 70g, Radix Platycodonis 70g, Herba Pogostemonis 70g, Rhizoma Zingiberis 35g, Radix Ginseng 35g.After drying, be crushed to 300 orders, after mix homogeneously, obtain raw material medicated powder.
By raw material medicated powder: dextrin=100:40g/g, by raw material medicated powder and dextrin mix homogeneously, using 70% ethanol as binding agent, wet granulation, dry, obtain drug particles.
By drug particles: magnesium stearate=100:4g/g, drug particles and lubricant are mixed, encapsulated, obtain capsule of the present invention.
The preparation of embodiment 5 pharmaceutical composition of the present invention
Rhizoma Atractylodis Macrocephalae 140g, Poria 260g, Semen Phaseoli 260g, Radix Astragali 195g, Herba Artemisiae Scopariae 195g, Herba Taraxaci 195g, Semen Armeniacae Amarum 130g, Radix Platycodonis 130g, Herba Pogostemonis 130g, Rhizoma Zingiberis 65g, Radix Ginseng 65g; After drying, be crushed to 500 orders, after mix homogeneously, obtain raw material medicated powder.
By raw material medicated powder: dextrin=100:30g/g, by raw material medicated powder and dextrin mix homogeneously, using water as binding agent, wet granulation, dry, obtain drug particles.
By drug particles: magnesium stearate=100:3g/g, drug particles and lubricant are mixed, encapsulated, obtain capsule of the present invention.
Beneficial effect of the present invention is shown further below by way of concrete test example.
Test example 1 pharmaceutical composition of the present invention is to the treatment of gastric ulcer
Gastric Ulcer standard: upper abdomen dull pain, dull pain or burn sample pain, alleviate after taking alkalescent medicine, such pain has rhythmicity, many appearance in 1 hour after the meal, alleviated gradually after 1 ~ 2 hour, generally also there will be acid regurgitation, belch, heartburn, the indigestion symptom such as Abdeminal pain, Nausea and vomiting; The visible niche of upper digestive tract radiography; Endoscopy, can in stomach see circle or oval, bottom is smooth, the ulcer of neat in edge, ulcer surface is greyish white or brown tongue film covers, edge swelling, color and luster ruddy, smooth and soft (i.e. gastric ulcer activity time).Accept 40 examples altogether for medical treatment, endoscopy confirms as gastric ulcer.
Criterion of cure: epigastrium pain disappears, endoscopy, and visible ulcer surface white fur disappears, become red congested cicatrix, visible pleat concentrates (i.e. cicatricial phase).
Effective standard: epigastrium pain disappears or alleviates, endoscopy, and tongue film is thinning, and ulcer reduces, the blush of visible mucous epithelium regeneration around it; Or ulcer surface almost disappears, it there is few thin coating (i.e. healing stage).
Therapeutic Method: get Rhizoma Atractylodis Macrocephalae 10g, Poria 10g, Semen Phaseoli 10g, Radix Astragali 7.5g, Herba Artemisiae Scopariae 7.5g, Herba Taraxaci 7.5g, Semen Armeniacae Amarum 5g, Radix Platycodonis 5g, Herba Pogostemonis 5g, Rhizoma Zingiberis 2.5g, Radix Ginseng 2.5g, decoct with water 3 times, first time adds 10 times amount soak by water 5 minutes, second time adds 8 times amount soak by water 10 minutes, and third time adds 8 times amount soak by water 15 minutes, filters, after merging decocting liquid, the every bu of gained decoction is taken for 3 times, period in a medicine, avoids eating anything raw or cold, maror.
Criterion of cure: take medicine continuously by Therapeutic Method, treats 20 ~ 40 days, cures 35 examples, accounts for 87% of total case; Effective 5 examples, account for 13% of total case.Total effective rate reaches 100%.
Test example 2 pharmaceutical composition of the present invention is to the treatment of duodenal ulcer
Duodenal ulcer diagnostic criteria: epigastrium dull pain, causalgia, distending pain or severe pain, also can be the only dull pain discomfort when hunger, or appearance is slight or rest pain under moderate xiphoid-process, can be alleviated by antacid or feed, early within 1 ~ 3 hour after the meal, start to occur upper abdominal pain, if do not taken medicine or taking food, just alleviate after continuing to lunch, food also must have meal to alleviate for latter 2 ~ 4 hours again bitterly.Endoscopy, thick fur and filthy, it can have petechia, sludged blood, and around the obvious congestion and edema of mucosa is rotten to the corn; Or tongue is still thicker, around mucosal inflammation edema alleviates, and red re-epithelialize (active stage) can appear in ulcer edge.Accept 30 examples altogether for medical treatment, endoscopy confirms as duodenal ulcer.
Therapeutic Method: with test example 1.
Criterion of cure: pain disappears, endoscopy, white fur disappears, and replaces red epithelium and cicatrix; Or re-epithelialize redness disappears, cicatrix color white (i.e. cicatricial phase).Take medicine continuously by Therapeutic Method, treat 15 ~ 20 days, cure 30 examples, account for 100% of total case.
Test example 3 pharmaceutical composition of the present invention is to the treatment of chronic erosive gastritis
Chronic erosive gastritis diagnostic criteria: occur the indigestion symptoms such as glutted, acid regurgitation, belch, irregularities stomachache, massive bleeding from upper digestive tract can be occurred, occur hematemesis, melena, shock, normal easily recurrence after stopped bleeding; Endoscopy, visible gastric mucosa congestion and edema, some lamellar is rotten to the corn, the multiple ulcer differed in size, ulcer surface can have fresh go out clot.Accept 22 examples altogether for medical treatment, endoscopy confirms as chronic erosive gastritis.
Therapeutic Method: with test example 1.
Criterion of cure: the indigestion symptom such as acid regurgitation, stomachache disappears, endoscopy, without point-like or lamellar erosion, mucosa edema disappears, and gastric mucosa heals.Take medicine continuously by Therapeutic Method, treat 20 ~ 30 days, cure 22 examples, account for 100% of total case.
Model case 1
Lee, man, 29 years old, when morning rises, distended tummy sense was obvious especially, and ante cibum 1, the phenomenon of belch, acid regurgitation appearred in hours, anorexia, and body weight obviously alleviates, painless; Through gastroscopy, confirm as erosive gastritis.
After taking medicine 7 days by test example 1 method, feeling of repletion, belch phenomenon are alleviated, and after 15 days, appetite has recovered suitable with normal period, acid regurgitation, belch phenomenon disappear, after 25 days, through gastroscopy, ulcer surface heals, and conscious appetite, stomach are felt good, and body weight is gone up.
The screening of test example 4 pharmaceutical composition of the present invention
Get SD rat, male and female half and half fasting is after 12 hours, rats by intraperitoneal injection 3% is anaesthetized without barbital sodium, to sterilize skin with alcohol cotton stick, cut abdominal cavity open, in glandular stomach portion, antetheca hole body intersection serosal surface sticks the circular filter paper 30s soaking into glacial acetic acid, diameter 5mm, repeat 3 times, close abdomen sewing-up cut, be coated with penicillin.Postoperative routine feeding, the 4th day by animal random packet, model group gavage 10mlkg
-1distilled water, positive drug ranitidine group gavage 30mgkg
-1, each screening group 10g crude drug/kg body weight (extracting method is with test example 1) of the present invention.The 2nd day after grouping starts gastric infusion, and administration every day 1 time, dosage is 10mlkg
-1, continuous 5 days, last administration is de-cervical vertebra execution animal after 12 hours, cut open the belly and get stomach, use brine gastric content, stomach is fixed in 10% formaldehyde, stomach is lain on glass surface ware after 15 minutes, measure major diameter and the minor axis of ulcer surface under magnifier with slide gauge, and calculate ulcer surface.
Calculate ulcer inhibition rate: ulcer inhibition rate=(matched group ulcer area-administration group ulcer area)/matched group ulcer area x100%, observe ulcer healing degree.
Experimental result is in table 1.
Table 1
Note: compared with model group, * is p<0.05, * * is p<0.01; Compared with group 4, △ is p<0.05
Wherein, the compatibility of each screening group is as follows:
Group 1: Rhizoma Atractylodis Macrocephalae 15g, Poria 15g, Semen Phaseoli 7g, Radix Astragali 5g, Herba Artemisiae Scopariae 5g, Herba Taraxaci 15g, Semen Armeniacae Amarum 8g, Radix Platycodonis 8g, Herba Pogostemonis 7g, Rhizoma Zingiberis 1g, Radix Ginseng 4g;
Group 2: Rhizoma Atractylodis Macrocephalae 12g, Poria 12g, Semen Phaseoli 12g, Radix Astragali 7.5g, Herba Artemisiae Scopariae 7.5g, Herba Taraxaci 10g, Semen Armeniacae Amarum 3g, Radix Platycodonis 3g, Herba Pogostemonis 10g, Rhizoma Zingiberis 4g, Radix Ginseng 5g;
Group 3: Rhizoma Atractylodis Macrocephalae 7g, Poria 7g, Semen Phaseoli 10g, Radix Astragali 9g, Herba Artemisiae Scopariae 10g, Herba Taraxaci 10g, Semen Armeniacae Amarum 5g, Radix Platycodonis 6g, Herba Pogostemonis 5g, Rhizoma Zingiberis 2.5g, Radix Ginseng 2.5g;
Group 4: Rhizoma Atractylodis Macrocephalae 10g, Poria 10g, Semen Phaseoli 10g, Radix Astragali 7.5g, Herba Artemisiae Scopariae 7.5g, Herba Taraxaci 7.5g, Semen Armeniacae Amarum 5g, Radix Platycodonis 5g, Herba Pogostemonis 5g, Rhizoma Zingiberis 2.5g, Radix Ginseng 2.5g.
Above-mentioned each group of compound recipe, flavour of a drug are identical, but medical material consumption proportion difference has appreciable impact to the drug activity of compound recipe: group 1-3, all has certain inhibitory action (p<0.05) to the gastric ulcer of animal pattern; But the prescription proportioning of employing group 4, can significantly improve the therapeutic activity of compound medicine, and its activity is significantly better than other each proportioning groups (p<0.05), and therefore, the present invention preferably organizes the prescription proportioning of 4.Above-mentioned test shows, pharmaceutical composition of the present invention, under specific proportioning, has played synergistic function.
Test example 5 pharmaceutical composition of the present invention is to the therapeutical effect of acetic acid type gastric ulcer
Get SD rat, fasting is after 12 hours, and rats by intraperitoneal injection 3% is anaesthetized without barbital sodium, to sterilize skin with alcohol cotton stick, cut abdominal cavity open, in glandular stomach portion, antetheca hole body intersection serosal surface sticks the circular filter paper 30s soaking into glacial acetic acid, diameter 5mm, repeat 3 times, close abdomen sewing-up cut, be coated with penicillin.Postoperative routine feeding, is divided into 6 groups at random by animal on the 4th day, and often organize 10, male and female half and half, are respectively model group (10mlkg
-1distilled water), pharmaceutical composition senior middle school of the present invention low dose group (be followed successively by 10,20,40g crude drug/kg body weight), contrast groups 1 (20g crude drug/kg body weight), contrast groups 2 (20g crude drug/kg body weight), positive drug ranitidine group (30mgkg
-1).The 2nd day after grouping starts gastric infusion, and administration every day 1 time, dosage is 10mlkg
-1, continuous 5 days, last administration is de-cervical vertebra execution animal after 12 hours, cut open the belly and get stomach, use brine gastric content, stomach is fixed in 10% formaldehyde, stomach is lain on glass surface ware after 15 minutes, measure major diameter and the minor axis of ulcer surface under magnifier with slide gauge, and calculate ulcer surface.
Calculate ulcer inhibition rate: ulcer inhibition rate=(matched group ulcer area-administration group ulcer area)/matched group ulcer area x100%, observe ulcer healing degree.
Pharmaceutical composition preparation method of the present invention: get Rhizoma Atractylodis Macrocephalae 10g, Poria 10g, Semen Phaseoli 10g, Radix Astragali 7.5g, Herba Artemisiae Scopariae 7.5g, Herba Taraxaci 7.5g, Semen Armeniacae Amarum 5g, Radix Platycodonis 5g, Herba Pogostemonis 5g, Rhizoma Zingiberis 2.5g, Radix Ginseng 2.5g, decoct with water 3 times, first time adds 10 times amount soak by water 5 minutes, second time adds 8 times amount soak by water 10 minutes, third time adds 8 times amount soak by water 15 minutes, filter, after merging decocting liquid, obtain decoction of the present invention.
The preparation method of contrast groups 1 medicine is as follows:
Get Fructus Amomi Rotundus 10g, Rhizoma Atractylodis Macrocephalae 20g, Poria 20g, Herba Pogostemonis 15g, Herba Taraxaci 15g, Radix Ginseng 5g, Folium Perillae 10g, Semen Armeniacae Amarum 10g, Semen Coicis 20g, Herba Artemisiae Scopariae 15g; Decoct with water 3 times, first time adds 10 times amount soak by water 5 minutes, and second time adds 8 times amount soak by water 10 minutes, and third time adds 8 times amount soak by water 15 minutes, filters, and after merging decocting liquid, obtains contrast groups 1 decoction.
The preparation method of contrast groups 2 medicine is as follows:
Semen Coicis 20 parts, Semen Benincasae 20 parts, Herba Artemisiae Scopariae 15 parts, the Rhizoma Atractylodis Macrocephalae 15 parts, Folium Perillae 10 parts, Semen Armeniacae Amarum 10 parts, Semen Lablab Album 10 parts, Semen Myristicae 10 parts, the Radix Astragali 10 parts, Radix Ginseng 5 parts, Fructus Forsythiae 5 parts.First add 4 times amount water soaking 10 minutes, then decoct with water 2 times, each 20 minutes, add water 10 times amount at every turn, filters, and after merging decocting liquid, obtains contrast groups 2 decoction.
Experimental result is in table 2.
Table 2
Note: compared with model group, * is p<0.05, * * is p<0.01; Compared with low dose group of the present invention, △ is p<0.05.
As shown in Table 2:
(1) pharmaceutical composition of the present invention, effectively can treat gastric ulcer, simultaneously, compared with contrast groups 1, although medicine composition is similar, but pharmaceutical composition of the present invention is all obviously being better than contrast groups 1 (p<0.05) compared with the drug activity under low dosage or Isodose;
(2) compared with contrast groups 2, the present invention is low dosage (10gKg comparatively
-1) time ulcer inhibitory action just suitable with contrast groups 2, during Isodose, drug activity of the present invention is more notable is better than contrast groups 2.
Above-mentioned experiment shows, pharmaceutical composition of the present invention, after the rational concerted application of drugs of screening, has played synergistic function.
Test example 6 pharmaceutical composition of the present invention is to the therapeutical effect of duodenal ulcer rat model
Get SD rat, male and female half and half, after anesthesia, by improvement Okabe method, get the glass tubing of internal diameter 3mm, vertical flicking on 0.5cm place duodenum antetheca serosal surface, injects 70% acetic acid 0.075ml, after 15s under pylorus in this pipe, sucking-off acetic acid, closes abdomen, obtains duodenal ulcer model.Postoperative 4 days, rat is divided into model group (10mlkg
-1distilled water), pharmaceutical composition senior middle school of the present invention low dose group (be followed successively by 10,20,40g crude drug/kg body weight), contrast groups (20g crude drug/kg body weight), positive drug omeprazole group (converting by quantity), gavage is after 7 days respectively, put to death rat, take out duodenum and observe ulcer inhibition rate.
Pharmaceutical composition preparation method of the present invention: get Rhizoma Atractylodis Macrocephalae 10g, Poria 10g, Semen Phaseoli 10g, Radix Astragali 7.5g, Herba Artemisiae Scopariae 7.5g, Herba Taraxaci 7.5g, Semen Armeniacae Amarum 5g, Radix Platycodonis 5g, Herba Pogostemonis 5g, Rhizoma Zingiberis 2.5g, Radix Ginseng 2.5g, decoct with water 3 times, first time adds 10 times amount soak by water 5 minutes, second time adds 8 times amount soak by water 10 minutes, third time adds 8 times amount soak by water 15 minutes, filter, after merging decocting liquid, obtain decoction of the present invention.
The preparation method of contrast groups 1 medicine is as follows:
Get Fructus Amomi Rotundus 10g, Rhizoma Atractylodis Macrocephalae 20g, Poria 20g, Herba Pogostemonis 15g, Herba Taraxaci 15g, Radix Ginseng 5g, Folium Perillae 10g, Semen Armeniacae Amarum 10g, Semen Coicis 20g, Herba Artemisiae Scopariae 15g; Decoct with water 3 times, first time adds 10 times amount soak by water 5 minutes, and second time adds 8 times amount soak by water 10 minutes, and third time adds 8 times amount soak by water 15 minutes, filters, and after merging decocting liquid, obtains contrast groups 1 decoction.
The preparation method of contrast groups 2 medicine is as follows:
Semen Coicis 20 parts, Semen Benincasae 20 parts, Herba Artemisiae Scopariae 15 parts, the Rhizoma Atractylodis Macrocephalae 15 parts, Folium Perillae 10 parts, Semen Armeniacae Amarum 10 parts, Semen Lablab Album 10 parts, Semen Myristicae 10 parts, the Radix Astragali 10 parts, Radix Ginseng 5 parts, Fructus Forsythiae 5 parts.First add 4 times amount water soaking 10 minutes, then decoct with water 2 times, each 20 minutes, add water 10 times amount at every turn, filters, and after merging decocting liquid, obtains contrast groups 2 decoction.
The results are shown in Table 3.
Table 3
Note: compared with model group, * is p<0.05, * * is p<0.01; Compared with low dose group of the present invention, △ is p<0.05.
As shown in Table 3, pharmaceutical composition of the present invention, effectively can treat duodenal ulcer, meanwhile, compared with contrast groups 1, although medicine composition is similar, but the drug activity of pharmaceutical composition of the present invention under Isodose is obviously better than contrast groups (p<0.05); Compared with contrast groups 2, the present invention is low dosage (10gKg comparatively
-1) time ulcer inhibitory action just suitable with contrast groups 2, during Isodose, drug activity of the present invention is more notable is better than contrast groups 2.
This just shows, pharmaceutical composition of the present invention, after the rational concerted application of drugs of screening, has played synergistic function.
Above-mentioned experiment shows, pharmaceutical composition of the present invention, after the rational concerted application of drugs of screening, has played synergistic function.
The particle diameter screening of test example 7 micro powder capsules agent of the present invention Raw medicated powder
Get SD rat, fasting is after 12 hours, and rats by intraperitoneal injection 3% is anaesthetized without barbital sodium, to sterilize skin with alcohol cotton stick, cut abdominal cavity open, in glandular stomach portion, antetheca hole body intersection serosal surface sticks the circular filter paper 30s soaking into glacial acetic acid, diameter 5mm, repeat 3 times, close abdomen sewing-up cut, be coated with penicillin.Postoperative routine feeding, is divided into 6 groups at random by animal on the 4th day, and often organize 10, male and female half and half, are respectively model group (10mlkg
-1distilled water), raw material medicated powder 300 order group (10 crude drugs/kg body weight) of the present invention, raw material medicated powder 350 order group (10 crude drugs/kg body weight) of the present invention, raw material medicated powder 400 order group (10 crude drugs/kg body weight) of the present invention, raw material medicated powder 450 order group (10 crude drugs/kg body weight) of the present invention, raw material medicated powder 500 order group (10 crude drugs/kg body weight) of the present invention, positive drug ranitidine group (30mgkg
-1).The 2nd day after grouping starts gastric infusion, and administration every day 1 time, dosage is 10mlkg
-1, continuous 5 days, last administration is de-cervical vertebra execution animal after 12 hours, cut open the belly and get stomach, use brine gastric content, stomach is fixed in 10% formaldehyde, stomach is lain on glass surface ware after 15 minutes, measure major diameter and the minor axis of ulcer surface under magnifier with slide gauge, and calculate ulcer surface.
Calculate ulcer inhibition rate: ulcer inhibition rate=(matched group ulcer area-administration group ulcer area)/matched group ulcer area x100%, observe ulcer healing degree.
Different-grain diameter raw material medicated powder group preparation method:
300 order groups: get Rhizoma Atractylodis Macrocephalae 10g, Poria 10g, Semen Phaseoli 10g, Radix Astragali 7.5g, Herba Artemisiae Scopariae 7.5g, Herba Taraxaci 7.5g, Semen Armeniacae Amarum 5g, Radix Platycodonis 5g, Herba Pogostemonis 5g, Rhizoma Zingiberis 2.5g, Radix Ginseng 2.5g, dry, pulverize to 300 orders, mix for subsequent use.
350 order groups: standby by 300 order prescription legal systems, only powder particle diameter is 350 orders.
400 order groups: standby by 300 order prescription legal systems, only powder particle diameter is 400 orders.
450 order groups: standby by 300 order prescription legal systems, only powder particle diameter is 450 orders.
500 order groups: standby by 300 order prescription legal systems, only powder particle diameter is 500 orders.
Experimental result is in table 4.
Table 4
Note: compared with model group, * is p<0.05, * * is p<0.01; Compared with 400 order groups, △ is p<0.05.
As shown in Table 4:
(1) micro powder capsules agent crude drug powder footpath of the present invention is when 300-500 order, can play good antiulcer activity equally.
(2) each for the present invention particle diameter group is carried out contrast known, when particle diameter is 400 order, the antiulcer activity of medicine of the present invention is significantly better than other particle diameter groups, and the present invention preferably uses the raw material medicated powder of 400 order particle diameters.
In sum, pharmaceutical composition of the present invention is after reasonable compatibility, pharmaceutical composition of the present invention has played synergistic function, can effectively treat gastric ulcer, duodenal ulcer and erosive gastritis, selects for clinical treatment peptic ulcer provides a kind of new medication.
Claims (9)
1. treat a micro powder capsules agent for peptic ulcer, it is characterized in that: it is by drug particles 100 weight portion, lubricant 1 ~ 5 weight portion, after mixing, prepares in incapsulating; Wherein, drug particles prepares by the following method:
(1) by following weight proportion weighting raw materials:
Rhizoma Atractylodis Macrocephalae 7-13 part, Poria 7-13 part, Semen Phaseoli 7-13 part, Radix Astragali 5-10 part, Herba Artemisiae Scopariae 5-10 part, Herba Taraxaci 5-10 part, Semen Armeniacae Amarum 3-7 part, Radix Platycodonis 3-7 part, Herba Pogostemonis 3-7 part, Rhizoma Zingiberis 2-3 part, Radix Ginseng 2-3 part;
(2) crude drug being crushed to particle diameter is 300-500 order, after mixing, obtains raw material medicated powder;
(3) according to raw material medicated powder: dextrin=100:20 ~ 50w/w, add dextrin and raw material medicated powder mixes, wet granulation, obtain drug particles.
2. crude drug according to claim 1, is characterized in that: crude drug weight proportion is as follows:
Rhizoma Atractylodis Macrocephalae 9-11 part, Poria 9-11 part, Semen Phaseoli 9-11 part, Radix Astragali 7-8 part, Herba Artemisiae Scopariae 7-8 part, Herba Taraxaci 7-8 part, Semen Armeniacae Amarum 4-6 part, Radix Platycodonis 4-6 part, Herba Pogostemonis 4-6 part, Rhizoma Zingiberis 2-3 part, Radix Ginseng 2-3 part.
3. crude drug according to claim 2, is characterized in that: crude drug weight proportion is as follows:
The Rhizoma Atractylodis Macrocephalae 10 parts, 10 parts, Poria, Semen Phaseoli 10 parts, the Radix Astragali 7.5 parts, Herba Artemisiae Scopariae 7.5 parts, Herba Taraxaci 7.5 parts, Semen Armeniacae Amarum 5 parts, Radix Platycodonis 5 parts, Herba Pogostemonis 5 parts, Rhizoma Zingiberis 2.5 parts, Radix Ginseng 2.5 parts.
4. the raw material medicated powder according to claim 1-3, is characterized in that: in step (2), powder particle diameter to 400 order.
5. micro powder capsules agent according to claim 1, is characterized in that: wet granulation adhesive therefor is selected from starch slurry, water or ethanol.
6. micro powder capsules agent according to claim 5, is characterized in that: described concentration of alcohol is 70%.
7. capsule according to claim 1, is characterized in that: described lubricant is selected from magnesium stearate or Pulvis Talci.
8. capsule according to claim 1, is characterized in that: described lubricant quantity is 2 ~ 4 parts, is preferably 3 parts.
9. the purposes of micro powder capsules agent in the medicine preparing gastric ulcer described in claim 1 ~ 8 any one.
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