CN105944104B - A kind of pharmaceutical composition for treating digestive tract ulcer - Google Patents
A kind of pharmaceutical composition for treating digestive tract ulcer Download PDFInfo
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- CN105944104B CN105944104B CN201610437162.0A CN201610437162A CN105944104B CN 105944104 B CN105944104 B CN 105944104B CN 201610437162 A CN201610437162 A CN 201610437162A CN 105944104 B CN105944104 B CN 105944104B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/426—1,3-Thiazoles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/54—Lauraceae (Laurel family), e.g. cinnamon or sassafras
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/61—Myrtaceae (Myrtle family), e.g. teatree or eucalyptus
Abstract
The present invention provides a kind of pharmaceutical composition for treating digestive tract ulcer comprising cloves cortex cinnamomi composition, bisfentidine and pharmaceutically acceptable carrier；And purposes of the pharmaceutical composition in preparation prevention and/or treatment digestive tract ulcer drug.
Description
Technical field
The invention belongs to pharmaceutical fields, and in particular to cloves, cortex cinnamomi and the manufactured composition with bisfentidine.
Background technique
Canker is a kind of common disease of digestive tract, can betide oesophagus, stomach or duodenum.Gastric ulcer is Digestive
System common disease, frequently-occurring disease, typical performance are hungry uncomfortable, glutted belch, pantothenic acid or the chronic middle upper abdomen of postprandial timing
Pain, visible melena and spitting blood when serious.Chinese medicine thinks that gastric ulcer belongs to " spleen deficiency ", " stomach is empty ", " deficiency-cold in spleen and stomach ", " gastral cavilty
Bitterly ", the scopes such as " acid regurgitation ", " gastric disorder causing nausea ", " vomiting ".
Bisfentidine can be highly selectively in conjunction with histamine H2-receptor, competitively antagonizing histamine and H2 receptor knot
Caused gastric acid secretion after conjunction generates Acidinhibitor.Gastric acid secretion can be effectively suppressed in bisfentidine, is used for peptic ulcer
Treatment.Bisfentidine includes Cimetidine, ranitidine, nizatidine, famotidine, Roxatidine etc..
The prior art there is no about cloves, cortex cinnamomi preparation or Flos Caryophylli extract and cinnamomum cassia extract, with H2 receptor antagonist
The fourths oil of bay preparations such as the report and fourth oil of bay soft capsule of agent composition or combination medicine and bisfentidine composition or
Combination medicine treats the report of ulcer or gastric ulcer.
Summary of the invention
It is an object of the present invention to provide a kind of pharmaceutical compositions for treating digestive tract ulcer；
It is another object of the present invention to provide use of the pharmaceutical composition in preparation treatment digestive tract ulcer drug
On the way；
Third object of the present invention is to provide a kind of medicine box for treating digestive tract ulcer.
The purpose of the present invention is what is be achieved through the following technical solutions:
As one aspect of the present invention, a kind of pharmaceutical composition is provided, the composition is by active constituent and selectable
Pharmaceutically acceptable carrier is made, and wherein the raw material of active constituent is made of cloves, cortex cinnamomi and bisfentidine.Wherein may be used
Selection refers to that the composition can not add pharmaceutically acceptable carrier, is only made of active constituent.
The weight ratio of the cloves, the total weight of cortex cinnamomi and bisfentidine is (0.25~4): 1；Preferably (1~
4): 1；Preferably 4:1 or 1:1.
The bisfentidine include Cimetidine, ranitidine, nizatidine, famotidine, in Roxatidine
Any one or two kinds of or two or more combinations.
The active part of cloves, cortex cinnamomi in the active constituent can choose cloves, cortex cinnamomi crushes to obtain or cloves,
Cortex cinnamomi is individually or obtained extract is extracted in merging；It is preferred that cloves, cortex cinnamomi are extracted volatile oil respectively, and by volatile clove oil,
Fourth oil of bay is obtained after Cortex Cinnamomi volatile oil mixing and cloves, cortex cinnamomi mixing extract obtained volatile oil (in this patent by cloves, cortex cinnamomi
It individually extracts mixed volatile oil and cloves, cortex cinnamomi mixes the volatile oil that extraction obtains as fourth oil of bay).
Above-mentioned fourth oil of bay, i.e. fourth oil of bay extract, be using cloves, cortex cinnamomi as raw material routinely extracting method extract to wave
Hair oil extract as main component；The cloves, cortex cinnamomi weight ratio be (0.2~5): 1, preferably 1:1；The routine mentions
Taking method includes steam distillation, extraction, circumfluence method, percolation, ultrasonic method etc.；The Extraction solvent includes water or organic
Solvent, the organic solvent include petroleum ether, ethyl acetate, n-butanol, acetone, ethyl alcohol or methanol；It is preferred that steam distillation
Or with petroleum ether extraction.
Preferably, in the fourth oil of bay, by weight percentage, the total content of eugenol and cinnaldehydrum is greater than or equal to
50%, preferably 50%-95%, further preferably 61%-85%, still more preferably 61%, 85%.
Described pharmaceutical composition can be prepared into oral preparation, such as tablet, hard capsule, soft capsule, granule, effervesce
Agent, suspension, powder, pulvis, dripping pill, microballoon, oral solution etc..
As another aspect of the present invention, the present invention also provides aforementioned pharmaceutical compositions to burst in preparation treatment alimentary canal
Purposes in ulcer drug.
As another aspect of the present invention, invention further provides a kind of medicine box, the medicine box includes that treatment has
The cloves cortex cinnamomi composite preparation and bisfentidine of effect amount.
The bisfentidine include Cimetidine, ranitidine, nizatidine, famotidine, in Roxatidine
The composition of any one or two or more.
The cloves cortex cinnamomi composite preparation is the composition crushed by cloves, cortex cinnamomi or the extract that extraction obtains
Tablet, hard capsule, soft capsule, granule, effervescent agent, suspension, powder, pulvis, dripping pill, the microballoon or oral being prepared into
The peroral dosage forms such as liquid；It is preferred that cloves, cortex cinnamomi are independent or merge soft capsule made of the fourth oil of bay for extracting and obtaining.
Above-mentioned fourth oil of bay, i.e. fourth oil of bay extract, be using cloves, cortex cinnamomi as raw material routinely extracting method extract to wave
Hair oil extract as main component；The cloves, cortex cinnamomi weight ratio be (0.2~5): 1, preferably 1:1；The routine mentions
Taking method includes steam distillation, extraction, circumfluence method, percolation, ultrasonic method etc.；The Extraction solvent includes water or organic
Solvent, the organic solvent include petroleum ether, ethyl acetate, n-butanol, acetone, ethyl alcohol or methanol；It is preferred that steam distillation
Or with petroleum ether extraction.
Preferably, in the fourth oil of bay, by weight percentage, the content of eugenol and cinnaldehydrum is greater than or equal to
50%, preferably 50%-95%, further preferably 61%-85%, still more preferably 61%, 85%.
Bisfentidine of the present invention, as ranitidine, Cimetidine can be used for treating duodenal ulcer, stomach is burst
The diseases such as ulcer, but have certain toxicity to liver, the infull patient of Liver and kidney function is used with caution, and furthermore has the absorption for reducing vitamin B12
Equal side effects.
" effective quantity " of the present invention or " therapeutically effective amount " refer to nontoxicity, but effect needed for the offer of sufficient amount
Drug or medicament.In combination therapy of the invention, in joint it is a kind of " effective quantity " of ingredient refer to the ingredient with other at
The amount of effect needed for effectively being provided when dividing use in conjunction." effective quantity " can be different due to the difference of subject, according to the age and
The ordinary circumstance of body, specific active medicine etc..Therefore, it is not possible to always refer to accurate " effective quantity ", however, any individual
Suitable " effective quantity " can be measured by the conventional experimental method of those of ordinary skill in the art's application in case.
" treatment " of the present invention refers to that the severity of symptom mitigates and/or frequency is reduced, and symptom and/or causes symptom
The elimination of reason, the generation of symptom and/or the prevention of their the reason of causing symptom, the improvement or correction of damage.
" administering drug combinations " of the present invention refer to giving pharmaceutical composition to object with certain dosage regimen, such as cloves cortex cinnamomi
Composition and bisfentidine simultaneously, respectively or are successively administered with different size unit dose.
Pharmaceutical acceptable carrier of the present invention includes filler, disintegrating agent, lubricant, suspending agent, adhesive, sweetener, rectifys
Taste agent, preservative, matrix etc..Filler include: starch, pregelatinized starch, lactose, mannitol, chitin, microcrystalline cellulose,
Sucrose etc.；Disintegrating agent include: starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, crosslinked polyvinylpyrrolidone,
Low-substituted hydroxypropyl cellulose, croscarmellose sodium etc.；Lubricant includes: magnesium stearate, lauryl sodium sulfate, talcum
Powder, silica etc.；Suspending agent includes: polyvinylpyrrolidone, microcrystalline cellulose, sucrose, agar, hydroxypropyl methyl cellulose
Deng；Adhesive includes: starch slurry, polyvinylpyrrolidone, hydroxypropyl methyl cellulose etc.；Sweetener includes: saccharin sodium, A Si
Pa Tan, sucrose, honey element, enoxolone etc.；Corrigent includes: sweetener and various essence；Preservative include: parabens,
Benzoic acid, sodium benzoate, sorbic acid and its esters, benzalkonium bromide, the fixed, eucalyptus oil of acetic acid chloroethene etc.；Matrix includes: PEG6000,
PEG4000, insect wax etc..
As another aspect of the present invention, the present invention further provides a kind of, Chinese medicine composition preparation synergy H2 by
Application in body antagonist for treating digestive tract ulcer drug, the bulk pharmaceutical chemicals of the Chinese medicine composition are made of cloves, cortex cinnamomi, fourth
Fragrant, cortex cinnamomi weight ratio is (0.2~5): 1.
The Chinese medicine composition can be prepared into clinically-acceptable dosage form, and preparation method includes that cloves cortex cinnamomi crushes to obtain
Composition or the obtained extract of the extraction tablet, hard capsule, soft capsule, the granule, effervescent agent, suspension that are prepared into
The peroral dosage forms such as agent, powder, pulvis, dripping pill, microballoon or oral solution.It is preferred that cloves, cortex cinnamomi are independent or merge the fourth extracted and obtained
Soft capsule made of oil of bay.The fourth oil of bay, i.e. fourth oil of bay extract are using cloves, cortex cinnamomi as the raw material routinely side of extraction
Method extract with volatile oil extract as main component；The cloves, cortex cinnamomi weight ratio be (0.2~5): 1, preferably 1:
1；The general extraction methods include steam distillation, extraction, circumfluence method, percolation, ultrasonic method etc.；The Extraction solvent
Including water or organic solvent, the organic solvent includes petroleum ether, ethyl acetate, n-butanol, acetone, ethyl alcohol or methanol；It is preferred that
Steam distillation or petroleum ether extraction.Preferably, in the fourth oil of bay, by weight percentage, eugenol and cinnaldehydrum
Total content be greater than or equal to 50%, preferably 50%-95%, further preferably 61%-85%, still more preferably
61%, 85%.
The present invention uses cloves cortex cinnamomi composition (preferably fourth oil of bay) and combination/pharmaceutical composition of bisfentidine
On the one hand object realizes the treatment of digestive tract ulcer synergistic effect, significantly improves to digestive tract ulcer, such as stomach
The therapeutic effect of ulcer；On the other hand the dosage that can effectively reduce ranitidine, Cimetidine, reduces H2 receptor antagonist
Side effect of the agent to liver kidney, while also reducing the dosage of fourth oil of bay or fourth oil of bay soft capsule etc..Joint of the invention is used
Drug and pharmaceutical composition can effectively reduce drug dosage while realizing therapeutic effect synergy, mitigate drug
Side effect reduces treatment drug expenditure, achieves unexpected technological progress.
Have after the main representative object Cimetidine of fourth oil of bay soft capsule and bisfentidine, ranitidine combination significant
Anti-peptic ulcer effect, better than group (p < 0.01 or p < 0.05) is applied alone, and can significantly reduce fourth oil of bay soft capsule and H2
The dosage of receptor antagonist.The combination medicine of fourth oil of bay soft capsule and bisfentidine of the present invention, which treats gastric ulcer, to be had
There is synergy.
Specific embodiment
The preparation of 1 fourth oil of bay of embodiment
Cloves 375g, cortex cinnamomi 375g are taken, 8 times of amount water are added, water proof distills 8 hours, collects volatile oil, refrigerates 24 hours, removes
Moisture is removed, altogether 36.0ml fourth oil of bay processed.Through detecting, the total content of eugenol and cinnaldehydrum accounts for the 85% of fourth oil of bay in extract.
Eugenol detection method:
Chromatographic condition: PEG-20M fused-silica capillary column (25m × 0.20mm × 0.33 μm), 175 DEG C of column temperature, FID inspection
Survey device, carrier gas: N2, flow velocity: 1mlmin-1Split sampling, split ratio: 45:1,1 μ L of sample volume.
The preparation of reference substance solution: taking eugenol reference substance about 10mg, accurately weighed, sets in 5mL measuring bottle, and precision is added just
Hexane dissolves and is diluted to scale, shakes up, as reference substance solution.
The preparation of test solution: fourth oil of bay about 50mg prepared by Example 1, it is accurately weighed, it sets in 25mL measuring bottle, essence
Close addition n-hexane dissolution is simultaneously diluted to scale, shakes up, as test solution.
The preparation of internal standard solution: taking biphenyl 10mg, sets in 25mL measuring bottle, and precision is added n-hexane dissolution and is diluted to scale,
It shakes up, as inner mark solution.
The investigation of linear relationship: precision weighs eugenol reference substance 102.70mg, sets in 10mL volumetric flask, adds n-hexane molten
Solve and be diluted to scale, it is accurate respectively measure 0.5,1.0,2.0,3.0,5.0mL in the volumetric flask of 25mL, add n-hexane to dilute
To scale.It is accurate respectively to draw 1.0 μ L, it injects in gas chromatograph, is measured by above-mentioned chromatographic condition.To inject eugenol
Measuring (X) is abscissa, and corresponding reference substance peak area (y) is ordinate, carries out linear regression, obtains regression equation.
Test solution is detected by GC conditions, value is will test and brings regression equation calculation into and obtain embodiment
Cloves phenol content in the fourth oil of bay of 1 preparation.
Cinnaldehydrum detection method:
Chromatographic condition: 2m × 3mm glass column (Japanese Shimadzu) fixer: 2%OV-17 carrier: 60~80 mesh
Chromosorbw (AW-DMCS), carrier: High Purity Nitrogen, flow velocity: 50ml/min, column temperature: 175 DEG C 220 DEG C of temperature of vaporization chamber, detection
180 DEG C of room temperature, detector FID.
The preparation of reference substance solution: precision weighs cinnaldehydrum 17.5ml in 25ml measuring bottle, CC14Dissolution is dissolved and is diluted
It to scale, shakes up, as reference substance solution.
The preparation of test solution: precision weighs the fourth oil of bay 25mg of the preparation of embodiment 1 in 50ml measuring bottle, uses CCl4It is molten
Scale is solved and be diluted to, is shaken up, as reference substance solution.
Linear relationship is investigated: 6 10ml measuring bottles number, sequentially add reference substance solution 0.5,1.0,2.0,3.0,4.0,
5.0ml uses CCl4Mutual scale is diluted, is shaken up.It is accurate respectively to draw 1.0 μ L, it injects in gas chromatograph, by color described in step 2
Spectral condition is detected, and is carried out linear regression to peak area (Y) with concentration (X), is obtained regression equation.
Test solution is detected by GC conditions, value is will test and brings regression equation calculation into and obtain embodiment
Determination of Cinnamaldehyde in the fourth oil of bay of 1 preparation.
The preparation of 2 fourth oil of bay of embodiment
In 1:1 ratio, totally 750 grams of cloves, cortex cinnamomi medicinal material are taken, adds 6 times of amount petroleum ethers, 50 DEG C of extraction 4h, is filtered, the dregs of a decoction are again
Add 4 times of amount petroleum ethers, 50 DEG C of extraction 4h, filter, merge petroleum ether extract, recycles petroleum ether, altogether 46.8ml fourth oil of bay processed.Through
It detects, the total content of eugenol and cinnaldehydrum accounts for the 61% of fourth oil of bay in extract.Detection method is referring to embodiment 1.
The preparation of 3 fourth oil of bay soft capsule of embodiment
Fourth oil of bay 3.6ml (25 DEG C of relative densities are 1.10g/ml) prepared by Example 1 is mixed with 36.4ml soybean oil,
It is spare.Gelatin 15g, glycerol 6g, simple syrup 1g are taken, deionized water 15g is added to mix, is heated to 60~70 DEG C, keeps the temperature 0.5 hour,
Methyl p-hydroxybenzoate 0.015g, ethyl-para-hydroxybenzoate 0.0075g is added, stirring vacuumizes, and 70 DEG C keep the temperature 20 points
Capsule material is made in clock.The mixture for taking fourth oil of bay and soybean oil is made soft capsule using pressing with capsule material, examines, packing, i.e.,
Obtain soft capsule 100, every dress 0.4g, the about 0.04g of oil of bay containing fourth).
The preparation of 4 fourth oil of bay tablet of embodiment
Fourth oil of bay 3ml prepared by Example 2, adds superfine silica gel powder 2.5mg, lactose 5.5mg, microcrystalline cellulose 5.3mg, sugar
Powder 3.0mg is pelletized with 10%PVP-k30 aqueous solution, additional low-substituted hydroxypropyl cellulose 0.5mg and magnesium stearate 0.2mg, pressure
Piece to get.
The preparation of 5 fourth oil of bay granule of embodiment
Fourth oil of bay 5ml prepared by Example 1, and be dissolved in a small amount of ethyl alcohol, it is spare.40g beta-cyclodextrin is taken, is added
300ml distilled water, heating water bath dissolution, temperature are added volatile oil ethanol solution when being down to 35 DEG C, are uniformly mixed, ultrasound inclusion
30min, refrigerated overnight filter, are deposited in 38 DEG C of low temperature dryings, obtain volatile oil beta cyclodextrin inclusion complex.By beta-cyclodextrin inclusion compound
Object is mixed with appropriate dextrin, uses 90% ethyl alcohol for wetting agent softwood, is crossed 20 meshes and is carried out wet granulation, 65 DEG C of dryings are whole
Grain to get.
The preparation of 6 fourth oil of bay soft capsule of embodiment
Fourth oil of bay 16g and 64g soybean oil prepared by Example 1 is mixed, spare.Take gelatin 18g, glycerol 5g, simple syrup
1g adds deionized water 15g to mix, and is heated to 65 DEG C, keeps the temperature 0.5 hour, methyl p-hydroxybenzoate 0.02g is added, to hydroxyl
Ethyl benzoate 0.001g, stirring, vacuumizes, and 75 DEG C keep the temperature 20 minutes, and capsule material is made.Take the mixing of fourth oil of bay and soybean oil
Object is made soft capsule using pressing with capsule material, examines, dispense to get soft capsule 100, every dress 0.4g, oil of bay containing fourth is about
0.16g)
Combination medicine/composite packaging medicine box preparation of 7 fourth oil of bay soft capsule of embodiment and ranitidine
Fourth oil of bay soft capsule prepared by Example 6, every oil of bay containing fourth about 0.16g.
Ranitidine Capsules, every contains 0.15 gram of ranitidine.
Composite packaging form: the soft capsule of oil of bay containing fourth 90, Ranitidine Capsules 30 in the packaging.
The composite tablet of embodiment 8 fourth oil of bay and Cimetidine
Fourth oil of bay 100g is prepared by 1 method of embodiment, and takes Cimetidine bulk pharmaceutical chemicals 100g, it is spare.Referring to embodiment 5
Method is only that 20 meshes in embodiment five are replaced with 50 meshes, prepares the fourth oil of bay particle of beta-cyclodextrin inclusion compound.By fourth oil of bay
Particle is mixed with Cimetidine bulk pharmaceutical chemicals with appropriate medical starch, microcrystalline cellulose, silica, is pressed into 500.
The compound capsule of embodiment 9 fourth oil of bay and Cimetidine
Fourth oil of bay 300g is prepared by 1 method of embodiment, and takes Cimetidine bulk pharmaceutical chemicals 200g, routinely preparation process is made
Capsule.
The compound granule of embodiment 10 fourth oil of bay and Cimetidine
Fourth oil of bay 200g is prepared by 1 method of embodiment, and takes Cimetidine bulk pharmaceutical chemicals 300g, routinely preparation process is made
Granule.
The composite tablet of embodiment 11 fourth oil of bay and ranitidine
Fourth oil of bay 100g is prepared by 1 method of embodiment, and takes ranitidine bulk pharmaceutical chemicals 100g, it is spare.Referring to embodiment 5
Method is only that 20 meshes in embodiment five are replaced with 50 meshes, prepares the fourth oil of bay particle of beta-cyclodextrin inclusion compound.By fourth oil of bay
Particle is mixed with ranitidine bulk pharmaceutical chemicals with appropriate medical starch, microcrystalline cellulose, silica, is pressed into 500.
The compound capsule of embodiment 12 fourth oil of bay and ranitidine
Fourth oil of bay 300g is prepared by 1 method of embodiment, and takes ranitidine bulk pharmaceutical chemicals 200g, routinely preparation process is made
Capsule.
The compound granule of embodiment 13 fourth oil of bay and ranitidine
Fourth oil of bay 200g is prepared by 1 method of embodiment, and takes ranitidine bulk pharmaceutical chemicals 300g, routinely preparation process is made
Granule.
The composite tablet of embodiment 14 fourth oil of bay and nizatidine
Fourth oil of bay 100g is prepared by 1 method of embodiment, and takes nizatidine bulk pharmaceutical chemicals 100g, it is spare.Referring to embodiment 5
Method is only that 20 meshes in embodiment five are replaced with 50 meshes, prepares the fourth oil of bay particle of beta-cyclodextrin inclusion compound.By fourth oil of bay
Particle is mixed with nizatidine bulk pharmaceutical chemicals with appropriate medical starch, microcrystalline cellulose, silica, is pressed into 500.
The compound capsule of embodiment 15 fourth oil of bay and nizatidine
Fourth oil of bay 300g is prepared by 1 method of embodiment, and takes nizatidine bulk pharmaceutical chemicals 200g, routinely preparation process is made
Capsule.
The compound granule of embodiment 16 fourth oil of bay and nizatidine
Fourth oil of bay 200g is prepared by 1 method of embodiment, and takes nizatidine bulk pharmaceutical chemicals 300g, routinely preparation process is made
Granule.
Treatment of 1 present composition of experimental example to water logging irritability rat gastric ulcer
1. experimental material
1.1 drug
Fourth oil of bay soft capsule (0.4g/): adult is 6/day with dosage, is prepared by embodiment 3.It takes in soft capsule
It is tolerant, it is prepared with 1.0% Tween 80 solution, places refrigerator and save backup.
Ranitidine Capsules (Lei Liya) (0.15g/): adult once a grain, 2 times a day, is made by Arstwyth (Foshan)
Medicine Co., Ltd provides, lot number 120608.Soft capsule content is taken, is prepared with 1.0% Tween 80 solution, it is standby to place refrigerator preservation
With.
Cimitidine Tablets (0.2g/ piece): one at a time, 2 times a day, being provided by Arstwyth (Foshan) pharmaceutical Co. Ltd,
Lot number 120107.Soft capsule content is taken, is prepared with 1.0% Tween 80 solution, refrigerator is placed and saves backup.
Fourth oil of bay soft capsule and Cimetidine and fourth oil of bay soft capsule and ranitidine combination medicine/pharmaceutical composition
The proportion of object is shown in Table 1；Dosage and concentration are calculated respectively with fourth oil of bay, ranitidine, Cimetidine.
1.2 animal
SD rat, half male and half female, weight 180-220g are provided by Chengdu University of Traditional Chinese Medicine's Experimental Animal Center, and animal is closed
Lattice card number moves pipe the 7th for river in fact.
2 methods and result
2.1 test method
Healthy SD rat is selected, weight 180-220g is divided into 8 groups by weight, gender stratified random, every group of 10 animals,
Grouping is shown in Table 1 with dosage.The daily gastric infusion of groups of animals is primary (dosage is shown in Table 1), continuous 15 days, prohibits after the last administration
Food 24 hours, then animal is fixed on metal cage by free water, be dipped vertically into 23 ± 0.5 DEG C of water.Immersion depth translation
Object xiphoid-process is horizontal, takes out after 24 hours, and dislocation of cervical vertebra is put to death.Abdominal cavity is opened, ligatures stomach cardia and pylorus and through stomach wall to gastral cavity
The formalin 8ml of interior injection 1%, stomach is taken out and is immersed in formalin, splits after 30 minutes along greater curvature, measures under magnifying glass
Gastric mucosa damage area calculates ulcer index by okabe method, and calculation method is as follows.
| Ulcer area (mm2) | 1-12 | 13-25 | 26-37 | 38-45 | >=50 or perforation |
| Ulcer index | 1 | 2 | 3 | 4 | 5 |
Ulcer inhibits percentage=control group ulcer index-administration group ulcer index/control group ulcer index × 100%
2.2 experimental result
To each group experimental result, statistical procedures between group are carried out, the results are shown in Table 1.
Table 1 to water logging irritability rat gastric ulcer model influence (N=10)
Note: compared with model control group*p<0.05、**p<0.01；Compared with fourth oil of bay soft capsule group#p<0.05、##p<
0.01。
Group (fourth oil of bay soft capsule group, Cimitidine Tablets group, Ranitidine Capsules group) is applied alone the results show that after administration in table 1
With the no significant difference (P > 0.05) of model group, and drug combination group (fourth oil of bay soft capsule+1,2 group of Cimitidine Tablets,
Fourth oil of bay soft capsule+1,2 group of Ranitidine Capsules) to rat water logging stress gastric ulcer significantly inhibit effect (p < 0.01, p <
0.05).Drug combination group has significant difference (p < 0.01, p < 0.05) compared with group is applied alone.
Treatment of the pharmaceutical composition of the present invention of experimental example 2 to pyloric ligation ulcers rat gastric ulcer
1. experimental material
1.1 drug
Fourth oil of bay soft capsule (0.4g/): adult is 6/day with dosage, is prepared by embodiment 3.It takes in soft capsule
It is tolerant, it is prepared with 1.0% Tween 80 solution, places refrigerator and save backup.
Ranitidine Capsules (Lei Liya) (0.15g/): adult once a grain, 2 times a day, is made by Arstwyth (Foshan)
Medicine Co., Ltd provides, lot number 120608.Soft capsule content is taken, is prepared with 1.0% Tween 80 solution, it is standby to place refrigerator preservation
With.
Cimitidine Tablets (0.2g/ piece): one at a time, 2 times a day, being provided by Arstwyth (Foshan) pharmaceutical Co. Ltd,
Lot number 120107.Soft capsule content is taken, is prepared with 1.0% Tween 80 solution, refrigerator is placed and saves backup.
Fourth oil of bay soft capsule and Cimetidine and fourth oil of bay soft capsule and ranitidine combination medicine/pharmaceutical composition
The proportion of object is shown in Table 2；Dosage and concentration are calculated respectively with fourth oil of bay, ranitidine, Cimetidine.
1.2 animal
SD rat, half male and half female, weight 180-220g are provided by Chengdu University of Traditional Chinese Medicine's Experimental Animal Center, and animal is closed
Lattice card number moves pipe the 7th for river in fact.
2 methods and result
2.1 test method
Healthy SD rat is selected, weight 180-220g is randomly divided into 8 groups by weight, gender, and every group of 10 animals are grouped
2 are shown in Table with dosage.The daily gastric infusion of groups of animals is primary (dosage is as shown in table 2), continuous 15 days, prohibits after the last administration
Food 48 hours, free water open abdominal cavity, ligature pylorus with ether by Animal Anesthesia.Postoperative 18 hours solutions take stomach, to stomach
The formalin 8ml of intracavitary injection 1%, stomach is taken out and is immersed in formalin, splits along greater curvature, sees after ten minutes under magnifying glass
A situation arises for stomach ulcer before examining, and by okabe method, calculates ulcer index, calculation method is as follows.
| Ulcer area (mm2) | 1-12 | 13-25 | 26-37 | 38-45 | >=50 or perforation |
| Ulcer index | 1 | 2 | 3 | 4 | 5 |
Ulcer inhibits percentage=control group ulcer index-administration group ulcer index/control group ulcer index × 100%
2.2 experimental result
To experimental result each group, statistical procedures between group are carried out, the results are shown in Table 2.
Table 2 to pyloric ligation ulcers rat gastric ulcer model influence (N=10)
Note: compared with model control group*p<0.05、**p<0.01；Compared with fourth oil of bay soft capsule group#p<0.05、##p<
0.01。
Group (fourth oil of bay soft capsule group, Cimitidine Tablets group, Ranitidine Capsules group) is applied alone the results show that after administration in table 2
With the no significant difference (P > 0.05) of model group, and drug combination group (fourth oil of bay soft capsule+1,2 group of Cimitidine Tablets,
Fourth oil of bay soft capsule+1,2 group of Ranitidine Capsules) (p is significantly inhibited to rat pylorus ligation gastric ulcer model
<0.01、p<0.05)。
The pharmaceutical composition of the present invention of experimental example 3 burns the treatment of type rat gastric ulcer to acetic acid
1. experimental material
1.1 drug
Fourth oil of bay soft capsule (0.4g/): adult is 6/day with dosage, by preparing by embodiment 3.Take soft capsule
Content is prepared with 1.0% Tween 80 solution, is placed refrigerator and is saved backup.
Ranitidine Capsules (Lei Liya) (0.15g/): adult once a grain, 2 times a day, is made by Arstwyth (Foshan)
Medicine Co., Ltd provides, lot number 120608.Soft capsule content is taken, is prepared with 1.0% Tween 80 solution, it is standby to place refrigerator preservation
With.
Cimitidine Tablets (0.2g/ piece): one at a time, 2 times a day, being provided by Arstwyth (Foshan) pharmaceutical Co. Ltd,
Lot number 120107.Soft capsule content is taken, is prepared with 1.0% Tween 80 solution, refrigerator is placed and saves backup.
Fourth oil of bay soft capsule and Cimetidine and fourth oil of bay soft capsule and ranitidine combination medicine/pharmaceutical composition
The proportion of object is shown in Table 3；Dosage and concentration are calculated respectively with fourth oil of bay, ranitidine, Cimetidine.
1.2 animal
SD rat, half male and half female, weight 180-220g are provided by Chengdu University of Traditional Chinese Medicine's Experimental Animal Center, and animal is closed
Lattice card number moves pipe the 7th for river in fact.
2 methods and result
2.1 test method
Healthy SD rat is selected, weight 180-220g, fasting 24 hours before testing, free water is beaten under etherization
Abdominal cavity is opened, 20% acetic acid solution 0.1ml is injected under glandular stomach portion antetheca sinus body intersection serous coat by exposure stomach.Reduction stomach, seam
Close stomach wall.Animal was divided into 8 groups by weight, gender stratified random in the 2nd day after operation, every group of 10 animals, grouping is shown in dosage
Table 3.The daily gastric infusion of groups of animals is primary (dosage is shown in Table 3), and continuous 15 days, fasting 24 was small after the last administration
When, free water is dead by Animal Anesthesia with excess diethyl ether, abdominal cavity is opened, solution takes stomach, is fixed with 1% formalin,
By okabe method, observation calculates ulcer index, and calculation method is as follows.
| Ulcer area (mm2) | 1-12 | 13-25 | 26-37 | 38-45 | >=50 or perforation |
| Ulcer index | 1 | 2 | 3 | 4 | 5 |
Ulcer inhibits percentage=control group ulcer index-administration group ulcer index/control group ulcer index × 100%
2.2 experimental result
To each group experimental result, statistical procedures between group are carried out, the results are shown in Table 3.
Table 3 acetic acid is burnt type rat gastric ulcer model influence (N=10)
Note: compared with model control group*p<0.05、**p<0.01；Compared with fourth oil of bay soft capsule group#p<0.05、##p<
0.01。
Group (fourth oil of bay soft capsule group, Cimitidine Tablets group, Ranitidine Capsules group) is applied alone the results show that after administration in table 3
With the no significant difference (P > 0.05) of model group, and drug combination group (fourth oil of bay soft capsule+1,2 group of Cimitidine Tablets,
Fourth oil of bay soft capsule+1,2 group of Ranitidine Capsules) type gastric ulcer model is burnt with significant inhibiting effect (p to rats acetic acid
< 0.01,0.05), compared with group is applied alone, have significant difference (p < 0.01,0.05).
The pharmaceutical composition of the present invention of experimental example 4 causes the treatment of rat pipe film injury to ethyl alcohol
1. experimental material
1.1 drug
Fourth oil of bay soft capsule (0.4g/): adult is 6/day with dosage, is prepared by embodiment 3.It takes in soft capsule
It is tolerant, it is prepared with 1.0% Tween 80 solution, places refrigerator and save backup.
Ranitidine Capsules (Lei Liya) (0.15g/): adult once a grain, 2 times a day, is made by Arstwyth (Foshan)
Medicine Co., Ltd provides, lot number 120608.Soft capsule content is taken, is prepared with 1.0% Tween 80 solution, it is standby to place refrigerator preservation
With.
Cimitidine Tablets (0.2g/ piece): one at a time, 2 times a day, being provided by Arstwyth (Foshan) pharmaceutical Co. Ltd,
Lot number 120107.Soft capsule content is taken, is prepared with 1.0% Tween 80 solution, refrigerator is placed and saves backup.
Fourth oil of bay soft capsule and Cimetidine and fourth oil of bay soft capsule and ranitidine combination medicine/pharmaceutical composition
The proportion of object is shown in Table 4；Dosage and concentration are calculated respectively with fourth oil of bay, ranitidine, Cimetidine.
1.2 animal
SD rat, half male and half female, weight 180-220g are provided by Chengdu University of Traditional Chinese Medicine's Experimental Animal Center, and animal is closed
Lattice card number moves pipe the 7th for river in fact.
2 methods and result
2.1 test method
Healthy SD rat is selected, weight 180-220g is divided into 8 groups by weight, gender stratified random, every group of 10 animals,
Grouping is shown in Table 5 with dosage.The daily gastric infusion of groups of animals is primary (dosage is shown in Table 4), and continuous 15 days, last dose
Fasting 48 hours afterwards, free water.Dehydrated alcohol (1ml/ is only) is gavaged when experiment, animal is put to death in dislocation of cervical vertebra after one hour, is beaten
Abdominal cavity is opened, solution takes stomach, fixes with 1% formalin, splits after 30 minutes along greater curvature, amplifies microscopic observation stomach ulcer
A situation arises, by okabe method, calculates ulcer index, calculation method is as follows
| Ulcer area (mm2) | 1-12 | 13-25 | 26-37 | 38-45 | >=50 or perforation |
| Ulcer index | 1 | 2 | 3 | 4 | 5 |
Ulcer inhibits percentage=control group ulcer index-administration group ulcer index/control group ulcer index × 100%
2.2 experimental result
To each group experimental result, statistical procedures between group are carried out, the results are shown in Table 4.
Table 4 to ethyl alcohol cause rat pipe film injury model influence (N=10)
Note: compared with model control group*p<0.05、**p<0.01；Compared with fourth oil of bay soft capsule group#p<0.05、##p<
0.01。
The no significant difference (P > 0.05) of group with model group is applied alone the results show that after administration in table 4, and combines and use
Medicine group (fourth oil of bay soft capsule+1,2 group of Cimitidine Tablets, fourth oil of bay soft capsule+1,2 group of Ranitidine Capsules) causes rat to ethyl alcohol
Gastric mucosa damage model has significant protective effect (p < 0.01,0.05).Drug combination group has significant compared with group is applied alone
Sex differernce (p < 0.011,0.05).
Claims (14)
1. a kind of pharmaceutical composition for treating digestive tract ulcer, which is characterized in that the composition is by active constituent and selectable
Pharmaceutically acceptable carrier is made, and wherein the raw material of active constituent is made of cloves, cortex cinnamomi and bisfentidine；The fourth
Fragrant, cortex cinnamomi weight ratio is 1:1；The weight ratio of cloves, the total weight of cortex cinnamomi and bisfentidine is 1:1 or 4:1；The H2
Receptor antagonist is Cimetidine or ranitidine.
2. pharmaceutical composition as described in claim 1, which is characterized in that wherein cloves, cortex cinnamomi be directly as active constituent, or
Cloves, cortex cinnamomi are individually or merging extracts obtained extract as active constituent.
3. pharmaceutical composition as claimed in claim 2, which is characterized in that cloves, cortex cinnamomi are extracted volatile oil respectively, and by fourth
Fourth oil of bay is obtained after fragrant volatile oil, Cortex Cinnamomi volatile oil mixing；Or the volatile oil that cloves, cortex cinnamomi mixing are extracted obtains fourth oil of bay.
4. pharmaceutical composition as claimed in claim 3, which is characterized in that in the fourth oil of bay, by weight percentage, cloves
The total content of phenol and cinnaldehydrum is greater than or equal to 50%.
5. pharmaceutical composition as claimed in claim 4, which is characterized in that in the fourth oil of bay, by weight percentage, cloves
The total content of phenol and cinnaldehydrum is 50%-95%.
6. pharmaceutical composition as claimed in claim 5, which is characterized in that in the fourth oil of bay, by weight percentage, cloves
The total content of phenol and cinnaldehydrum is 61%-85%.
7. pharmaceutical composition as claimed in claim 6, which is characterized in that in the fourth oil of bay, by weight percentage, cloves
The total content of phenol and cinnaldehydrum is 61% or 85%.
8. a kind of Chinese medicine composition preparation synergy bisfentidine treatment digestive tract ulcer drug in application, it is described in
The bulk pharmaceutical chemicals of drug composition are made of cloves, cortex cinnamomi, cloves, cortex cinnamomi weight ratio be 1:1；Cloves, the total weight of cortex cinnamomi and H2
The weight ratio of receptor antagonist is 1:1 or 4:1；Bisfentidine is Cimetidine or ranitidine.
9. a kind of medicine box, which is characterized in that the medicine box includes the cloves cortex cinnamomi composite preparation and H2 receptor of therapeutically effective amount
Antagonist formulation；Cloves in the cloves cortex cinnamomi composite preparation, cortex cinnamomi weight ratio be 1:1；Cloves cortex cinnamomi composite preparation
Weight ratio with bisfentidine preparation is 1:1 or 4:1；Bisfentidine preparation is Cimetidine or ranitidine.
10. medicine box as claimed in claim 9, which is characterized in that the cloves cortex cinnamomi composite preparation is by cloves, ground cinnamon
Tablet that the extract that broken obtained composition or extraction obtain is prepared into, hard capsule, soft capsule, granule, effervescent agent,
Suspension, powder, pulvis, dripping pill, microballoon or oral solution.
11. medicine box as claimed in claim 10, which is characterized in that the cloves cortex cinnamomi composite preparation is cloves, cortex cinnamomi list
Solely or soft capsule prepared by obtained fourth oil of bay is extracted in merging.
12. medicine box as claimed in claim 11, which is characterized in that in the fourth oil of bay, by weight percentage, eugenol and
The total content of cinnaldehydrum is greater than or equal to 50%.
13. medicine box as claimed in claim 12, which is characterized in that in the fourth oil of bay, by weight percentage, eugenol and
The total content of cinnaldehydrum is 50%-95%.
14. medicine box as claimed in claim 13, which is characterized in that in the fourth oil of bay, by weight percentage, eugenol and
The total content of cinnaldehydrum is 61%-85%.
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| JP2004175757A (en) * | 2002-11-28 | 2004-06-24 | Chugai Pharmaceut Co Ltd | Medicinal composition |
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