CN110151739A - The application of β-patchoulene and the application including β-patchoulene pharmaceutical composition - Google Patents
The application of β-patchoulene and the application including β-patchoulene pharmaceutical composition Download PDFInfo
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Abstract
The present invention relates to biomedicine field, the application in particular to a kind of β-patchoulene and the application including β-patchoulene pharmaceutical composition.Application of the pharmaceutical composition in preparation prevention and/or treatment acute gastric ulcer drug；Effective component includes β-patchoulene；β-patchoulene preparation method includes: that Patchoulicalcohol reacts in organic solvent with acid, with nonpolar solvent extraction reaction product, then using Patchoulicalcohol and hydrochloric acid dehydration is occurred into for extract liquor with chromatography post separation, obtains β-patchoulene, this method yield is up to 80%；And β-patchoulene purity is high that product can be easily separated, obtain.Patchoulene is prepared by raw material of Patchoulicalcohol, raw material is easy to get, and reduces the program in preparation process, increases the application of patchoulene.In addition, β-patchoulene is applied in the drug for preventing and/or treating acute gastric ulcer, increase the new purposes of β-patchoulene, promotes its industry, commercialization.
Description
The application be submit on 06 16th, 2017, on 06 16th, 2017 applying date, entitled " a kind of β-is wide
Preparation method, pharmaceutical composition and the application of wrinkled giant hyssop alkene ", point application No. is the application for a patent for invention of CN201710458440.5
Case application.
Technical field
The present invention relates to biomedicine fields, preparation method, pharmaceutical composition in particular to a kind of β-patchoulene
Object and application.
Background technique
β-patchoulene, one of the natural sesquiterpene ingredient being present in Pogostemon cablin, molecular formula C15H24, molecular weight
It is 204.36.Appearance is pale yellow oily liquid, not soluble in water, is soluble in the common organic solvent such as ethyl alcohol, petroleum ether.Currently,
Researcher is considerably less to the research of patchoulene.Inventor has found that β-patchoulene can be by rectifying-column chromatography method from the wide leaves of pulse plants
Sesame oil extract it is isolated, but patchouli oil to prepare β-patchoulene content in raw material Pogostemon cablin medicinal material different because of the place of production,
And content is relatively low, and β-patchoulene is only obtained from patchouli oil, and the application of β-patchoulene is not utilized to carry out.
Summary of the invention
The purpose of the present invention is to provide a kind of β-patchoulene and preparation method thereof, pharmaceutical composition and application, purports
The problem of preparing is not easy improving existing β-patchoulene.
The present invention provides a kind of technical solution:
A kind of preparation method of β-patchoulene comprising: Patchoulicalcohol reacts in organic solvent with acid, with nonpolarity
Solvent extraction reaction product, then by extract liquor chromatography post separation.
Further, above-mentioned Patchoulicalcohol reacts in organic solvent with acid, and organic solvent is ethyl alcohol or methanol.
Further, above-mentioned nonpolar solvent is n-hexane or petroleum ether.
Further, above-mentioned with chromatographic column separating and extracting liquid includes separating extract liquor with silica gel column chromatography, is then used
Property aluminum oxide column chromatography separation.
Further, the packing material size of above-mentioned silicagel column is 200~300 mesh；The packing material size of neutral alumina column is 200
~300 mesh.
Further, it with chromatographic column separating and extracting liquid, is eluted using apolar substance.
Further, above-mentioned acid is hydrochloric acid or sulfuric acid.The present invention also provides a kind of technical solutions:
A kind of β-patchoulene is made by above-mentioned β-patchoulene preparation method.
The present invention also provides a kind of technical solutions:
A kind of pharmaceutical composition, effective component include above-mentioned β-patchoulene.
Further, above-mentioned pharmaceutical composition further includes pharmaceutically acceptable carrier or auxiliary material.
The present invention also provides a kind of technical solutions:
Application of the above-mentioned pharmaceutical composition in preparation prevention and/or treatment acute gastric ulcer drug.
Preparation method, pharmaceutical composition and the beneficial effect of application of a kind of β-patchoulene provided in an embodiment of the present invention
It is:
Dehydration is occurred using Patchoulicalcohol and hydrochloric acid, obtains β-patchoulene, this method yield is up to 80%；And it produces
β-patchoulene purity is high that object can be easily separated, obtain.Patchoulene is prepared by raw material of Patchoulicalcohol, raw material is easy to get, and reduces
Program in preparation process increases the application of patchoulene.
In addition, β-patchoulene is applied in the drug for preventing and/or treating acute gastric ulcer, increase β-patchoulene
New purposes promotes its industry, commercialization.
Detailed description of the invention
In order to illustrate the technical solution of the embodiments of the present invention more clearly, below will be to needed in the embodiment attached
Figure is briefly described, it should be understood that the following drawings illustrates only certain embodiments of the present invention, therefore is not construed as pair
The restriction of range for those of ordinary skill in the art without creative efforts, can also be according to this
A little attached drawings obtain other relevant attached drawings.
Fig. 1 is the mass spectrogram of 1 synthetic product of the embodiment of the present invention；
Fig. 2 is the hydrogen nuclear magnetic resonance spectrogram of 1 synthetic product of the embodiment of the present invention；
Fig. 3 is the carbon-13 nmr spectra figure of 1 synthetic product of the embodiment of the present invention；
Fig. 4 is influence of the β-patchoulene to dehydrated alcohol induced rat gastric ulcer area and inhibiting rate；
Fig. 5 is histological scores of the β-patchoulene to dehydrated alcohol induced rat acute gastric mucosal injury；
Fig. 6 shows the influence of Indomethacin induced rat gastric ulcer area and inhibiting rate；
Fig. 7 shows β-patchoulene to the histological scores of Indomethacin induced rat acute gastric mucosal injury.
Specific embodiment
β-patchoulene is a kind of class compound difficult to understand.It is a kind of special sequiterpene, with 5 member rings and the conjunction of 7 member ring a pair of horses going side by sides
At aromatic skeleton.Its molecular formula is C15H24, molecular weight 204.36, structural formula is as follows:
β-patchoulene can be extracted by rectifying-column chromatography method from patchouli oil isolated at present.Separation preparation step
It is rapid as follows:
Add 700.00g patchouli oil to enter rectifying tower bottom (pressure 6kPa), is heated to kettle temperature and reaches 135.0 DEG C
When, patchouli oil comes to life and flows back, and keeps temperature and vacustat, after making its infinite reflux 3h, continues heating and rises
Temperature.Reflux ratio is adjusted, distillate is acquired and analyzes fraction, collects the sample of different temperature zones.Finally merge β-patchoulene to contain
Measure the fraction up to 80% or more.
But separating and extracting beta-patchoulene from patchouli oil, it is difficult remaining in β-patchoulene and patchouli oil
Component separation.Further, it is extracted and is obtained from Pogostemon cablin due to patchouli oil, β-patchoulene in raw material Pogostemon cablin medicinal material
Content is different because of the place of production, and content of the β-patchoulene in Pogostemon cablin is lower, leads to β-patchoulene made from above-mentioned method
Low output.
It in order to make the object, technical scheme and advantages of the embodiment of the invention clearer, below will be in the embodiment of the present invention
Technical solution be clearly and completely described.The person that is not specified actual conditions in embodiment, according to normal conditions or manufacturer builds
The condition of view carries out.Reagents or instruments used without specified manufacturer is the conventional production that can be obtained by commercially available purchase
Product.
β-patchoulene of the embodiment of the present invention and preparation method thereof, pharmaceutical composition and application are carried out specifically below
It is bright.
A kind of preparation method of β-patchoulene comprising Patchoulicalcohol reacts in organic solvent with acid, with nonpolarity
Solvent extraction reaction product, then by extract liquor chromatography post separation.
Patchoulicalcohol is synthesized β-patchoulene using synthetic method by the present invention, and reaction structure formula and mechanism are as follows:
It is used as catalyst using acid, Patchoulicalcohol generation dehydration, it is higher to obtain β-patchoulene yield, through inventor
Detection to experimental result, β-patchoulene yield are up to 80%.Using nonpolar solvent to reaction product after fully reacting
Extraction.In preferred embodiments of the present invention, reaction product is repeatedly extracted, after the extract liquor repeatedly extracted is merged
Concentration.The isolated product β-patchoulene of chromatographic column is used after concentration.
Further, above-mentioned organic solvent is ethyl alcohol or methanol.It should be noted that in the other embodiment of the present invention
In, Patchoulicalcohol can also be in the organic solvent that other can dissolve Patchoulicalcohol with reacting for acid solution, it is preferable that this is organic
Solvent is alcohols.
Further, the amount ratio of above-mentioned Patchoulicalcohol and ethanol solution be 1~10mg/mL, specifically, Patchoulicalcohol with
Ethanol solution amount ratio is 4-6mg/mL.
Further, above-mentioned acid solution is aqueous hydrochloric acid solution or aqueous sulfuric acid.Preferably, above-mentioned hydrochloric acid is dilute salt
Acid, further, the volume fraction of dilute hydrochloric acid are 10%；The volume and the ratio between Patchoulicalcohol and ethyl alcohol total volume of dilute hydrochloric acid are as follows:
3:2.In other embodiments of the invention, above-mentioned acid can also be other acid such as acetic acid, boric acid.
Further, in order to which the reaction process for accelerating Patchoulicalcohol and acid solution should in preferred embodiments of the present invention
The reaction temperature of reaction is 35 DEG C -40 DEG C, reaction carries out in the oscillator that revolving speed is 120~220rpm.
In preferred embodiments of the present invention, above-mentioned nonpolar solvent is n-hexane or petroleum ether.In other embodiments,
Above-mentioned nonpolar solvent can also be hexamethylene, the lower solvent of carbon tetrachloride isopolarity.
Further, above-mentioned chromatographic column separating step includes separating extract liquor with silica gel column chromatography, then uses neutral oxygen
Change aluminium pillar layer separation.Preferably, the packing material size of silicagel column is 200~300 mesh；The packing material size of neutral alumina column is
200~300 mesh.
From the above, by extract liquor chromatography column separation, using apolar substance.Further, in the present invention
In preferred embodiment, eluent is n-hexane.In other embodiments, above-mentioned eluent can also be other non-poles such as petroleum ether
Property substance.
Further, in preferred embodiments of the present invention, the concrete operations of β-patchoulene are synthesized using Patchoulicalcohol
Steps are as follows:
Container equipped with dilute hydrochloric acid is placed on oscillator, at 37 DEG C, vibrates under conditions of 220rpm, is added into container
The ratio of Patchoulicalcohol-ethanol solution, Patchoulicalcohol and ethyl alcohol is 10mg/mL；After complete reaction, with isometric n-hexane
Reaction product is extracted 3 times, combining extraction liquid, concentrated by rotary evaporation obtains mixture.
Mixture is separated with the neutral aluminum oxide column chromatography of the silica gel column chromatography of 300 mesh and 300 mesh respectively, is used
N-hexane elution, merges eluent, concentrated by rotary evaporation.
The present invention also provides a kind of technical solutions:
A kind of β-patchoulene is made by above-mentioned β-patchoulene preparation method.
Inventor's research and experiment discovery, β-patchoulene can treat acute gastric ulcer.β-patchoulene has prevention and treatment
The bioactivity of acute gastric ulcer.
The present invention also provides a kind of technical solutions:
A kind of pharmaceutical composition, effective component include above-mentioned β-patchoulene.
Further, one or more solids or liquid pharmaceutical excipients and/or adjuvant can be added in above-mentioned drug
In conjunction with being made and can be used as people with administration form appropriate or dosage form.
Pharmaceutical composition provided by the invention can dosage forms for administration, administration route can be enteron aisle or non-enteric as unit of
Road, such as it is nasal cavity, subcutaneous, muscle, oral.Correspondingly, form of administration such as tablet, capsule, aerosol, pill, pulvis, solution
Agent etc..It can be ordinary preparation, sustained release preparation, controlled release preparation etc..
In preferred embodiments of the present invention, aforementioned pharmaceutical compositions further include pharmaceutically acceptable carrier or auxiliary material.
In order to which unit dosage forms for administration is supported tablet, various carriers well known in the art can be widely used.About carrier
Example, diluent and absorbent；Such as starch, dextrin, lactose, sucrose, alumina silicate.Wetting agent and adhesive, it is Ru Shui, sweet
Oil, polyethylene glycol, gelatine size, methylcellulose etc..Disintegrating agent, such as alginate, agar powder, sodium bicarbonate, dodecyl
Sodium sulfonate etc..
From the above, in order to which injection preparation is made in administration unit, such as solution, emulsion, freeze drying powder injection or suspension
Agent can use all diluents commonly used in the art, such as water, ethyl alcohol, 1,3-PD, polyoxy ethylene sorbitol fatty acid
Deng.In addition, suitable sodium chloride, glucose or glycerol can be added into injection preparation in order to prepare isotonic injection, with
And conventional cosolvent, buffer, pH adjusting agent etc..
The dosage of pharmaceutical composition provided in an embodiment of the present invention depends on many factors, such as to be prevented or be controlled
Treat gender, age, weight and the individual reaction of the property and severity of disease, patient or animal.Specificization used
Close object, administration route and administration number of times etc..Further, above-mentioned dosage can for single dose or be divided into it is several, such as two, three
Or four dosage forms for administration.
The present invention also provides a kind of technical solutions:
Application of the above-mentioned pharmaceutical composition in preparation prevention and/or treatment acute gastric ulcer drug.
Feature and performance of the invention are described in further detail with reference to embodiments.
Embodiment 1
The present embodiment provides a kind of β-patchoulenes, are mainly made by following steps:
Container equipped with dilute hydrochloric acid is placed on oscillator, at 37 DEG C, vibrates under conditions of 120rpm, is added into container
The ratio of Patchoulicalcohol-ethanol solution, Patchoulicalcohol and ethyl alcohol is 1mg/mL；The volume fraction of dilute hydrochloric acid is 10%；Dilute hydrochloric acid
The ratio between with Patchoulicalcohol-ethanol solution volume are as follows: 3:2.After complete reaction, reaction product is extracted with isometric n-hexane
It takes 2 times, combining extraction liquid, concentrated by rotary evaporation obtains mixture.
Mixture is separated with the neutral aluminum oxide column chromatography of the silica gel column chromatography of 200 mesh and 200 mesh respectively, is used
N-hexane elution, merges eluent, concentrated by rotary evaporation.
Embodiment 2
The present embodiment provides a kind of β-patchoulenes, are mainly made by following steps:
Container equipped with dilute hydrochloric acid is placed on oscillator, at 35 DEG C, vibrates under conditions of 220rpm, is added into container
The ratio of Patchoulicalcohol, methanol solution, Patchoulicalcohol and methanol is 6mg/mL；The volume fraction of dilute hydrochloric acid is 8%；Dilute hydrochloric acid with
The ratio between Patchoulicalcohol-methanol solution volume are as follows: 1:1.After complete reaction, reaction product is extracted with isometric petroleum ether
3 times, combining extraction liquid, concentrated by rotary evaporation obtains mixture.
Mixture is separated with the neutral aluminum oxide column chromatography of the silica gel column chromatography of 300 mesh and 300 mesh respectively, is used
N-hexane elution, merges eluent, concentrated by rotary evaporation.
Embodiment 3
The present embodiment provides a kind of β-patchoulenes, are mainly made by following steps:
Patchoulicalcohol reacts in methanol solution with hydrochloric acid, and the ratio of Patchoulicalcohol and methanol is 6mg/mL；Hydrochloric acid it is dense
Degree is 10%, the ratio between dilute hydrochloric acid and Patchoulicalcohol-methanol solution volume are as follows: 2:1.After complete reaction, petroleum ether is to reaction
Product extraction is separated extract liquor using the silica gel column chromatography of 300 mesh and the neutral aluminum oxide column chromatography of 300 mesh, used
N-hexane elution, is concentrated after merging eluent.
Embodiment 4
The present embodiment provides a kind of pharmaceutical composition, which includes β-patchoulene that embodiment 1 obtains.
Specifically, β-patchoulene 400g that Example 1 obtains is added lactose 480g, starch 754g and is uniformly mixed, uses
7% starch slurry 350g is added magnesium stearate 16g and mixes as adhesive, wet granulation, drying, is pressed into every wide containing β-
The tablet of wrinkled giant hyssop alkene 40mg, every net weight 0.2g.
Embodiment 5
The present embodiment provides a kind of pharmaceutical composition, which includes β-patchoulene that embodiment 1 obtains.
The β that Example 1 obtains-patchoulene 200g is added lactose 980g, starch 1254g and is uniformly mixed, with 7%
Starch slurry 350g is added magnesium stearate 16g and mixes as adhesive, wet granulation, drying, and filling to No. 1 capsule is made 10000
Grain, every capsule include β-patchoulene 20mg, every net weight 0.3g.
Embodiment 6
The present embodiment provides a kind of pharmaceutical composition, which includes β-patchoulene that embodiment 1 obtains.
Appropriate PEG4000 is added as matrix in the β that Example 1 obtains-patchoulene 300g, and appropriate amount of fluid paraffin is
Coolant；Dropping preparation method is made containing every ball containing β-patchoulene 6mg dripping pill, every ball net weight 30mg.
Embodiment 7
β-patchoulene 100g that embodiment 1 obtains is weighed, is added in appropriate beta-cyclodextrin and inclusion compound is made, is added suitable
Lactose, microcrystalline cellulose, starch slurry are measured, is uniformly mixed, is gradually added into second alcohol and water, particle is made, dispensed.Specification is every
Comprising β-patchoulene 40mg granule, every packet net weight 7g.
Embodiment 8
β-patchoulene 100g that embodiment 1 obtains is weighed, solubilizer Tween 80 and a certain proportion of ethyl alcohol is added, fills
Divide and stirs evenly；Then xylitol is added as corrigent, is uniformly dissolved, content is fitted into oral liquid glass bottle by filtration clarification,
Sterilizing.Specification is every bottle containing β-patchoulene 40mg oral solution, every bottle of net content 10mL.
Test example 1
The product (β-patchoulene) obtained to embodiment 1 carries out mass spectrum, magnetic resonance detection, testing result such as Fig. 1-figure
Shown in 3, Fig. 1 is the mass spectrogram of product；Fig. 2 is the nuclear magnetic resonance spectroscopy of product；Fig. 3 is the carbon-13 nmr spectra of product.According to
The data of Fig. 1-Fig. 3 illustrate the embodiment of the present invention it is found that the structure and molecular weight of obtained product are identical as β-patchoulene
Product made from 1 is β-patchoulene；Further illustrate that product made from preparation method of the invention is β-patchoulene.
Test example 2
SPF grades of male SD rats are taken, weighs, is randomly divided into normal group (Intact), model group (Vehicle), Lan Suola
Azoles group (LSZ, 200mg/kg), β-patchoulene (β-PAE) low, middle and high dose groups (matched doses 10,20,40mg/kg),
Every group 8.After grouping, label, then each rat body weight is weighed, record and calculate corresponding administered volume (1mL/100g).Except normal
Group and model group give 0.5%Tween-80 solution, other groups give corresponding drug therapy, and daily gastric infusion 1 time connects
Continuous administration 7 days.In 1 hour after the last administration, every rat oral gavage dehydrated alcohol (0.5mL/100g) caused Acute Gastric Mucosal to damage
Wound, rat needs fasting 24 hours before modeling, free water.After stomach-filling dehydrated alcohol 1 hour, each rat euthanasia is taken out complete
Stomach cuts off stomach wall along greater curvature, cleans gastric content, and expansion gastric tissue is placed between two pieces of glass plates and fixes for taking pictures.With
ImageJ image analysis software (1.47v, National Institutes of Health, USA) calculates ulcer area, and counts
Calculate inhibiting rate.Inhibiting rate (%)=(model group ulcer area-administration group ulcer area)/model group ulcer area × 100%.
0.5cm × 0.5cm gastric tissue is taken in same area, is fixed on 4% paraformaldehyde solution, conventional film-making, hematoxylin-eosin dye
Color is observed and is taken pictures under microscope (OLYMPUS BX53 fluorescence microscope), and You Sanwei Pathology Doctors ' is using independent scoring.
Reference literature carries out the histology pathological score of stomach lining inflammation and degree of injury and calculates total score；Wherein, it scores
Standard is as shown in table 1.
The pathological score standard of 1 gastric mucosa inflammation of table and degree of injury
Each data are indicated with mean ± standard deviation (mean ± SD), are charted using Graphpad Prism7 software,
SPSS20.0 software carries out statistical analysis, comparison in difference between each group, using one-way analysis of variance (One-Way ANOVA),
When variance is neat, Multiple range test uses LSD method two-by-two between group.When heterogeneity of variance, Multiple range test uses Dunnett ' s two-by-two between group
T3 method.It is standard with P < 0.05, indicates significant difference.Normal group is examined compared with model group using independent sample T
(Student's t test).Compared with normal group, #:P < 0.05, ##:P < 0.01；Compared with model group, *: P < 0.05, * *: P
<0.01。
Influence of the β-patchoulene to dehydrated alcohol induced rat gastric ulcer area and inhibiting rate is as shown in Figure 4；Fig. 5 is β-
Histological scores of the patchoulene to dehydrated alcohol induced rat acute gastric mucosal injury.
Rat normal gastric mucosa structural integrity, mucous membrane surface foveolae gastricae is high-visible, the close rule of body of gland arrangement in mucous membrane,
Epithelium, which has no, to fall off, and body of gland has no damage, and lamina propria has no bleeding and cell infiltration.Model group gastric mucosa damage relatively depth and face
Product is larger, and foveolae gastricae structure is destroyed, and oedema and inflammatory infiltration occurs, and a large amount of epithelial cell denaturation fall off, is rotten to the corn, gland structure
Disorder, some missings, lamina propria are shown in moderate bleeding (general comment is divided into 10.39 ± 0.77).Lansoprazole group stomach lining is complete, epithelium
It has no and falls off, body of gland has no damage, and lamina propria has no bleeding and cell infiltration (general comment is divided into 6.56 ± 0.62).
By Fig. 4, Fig. 5: β-patchoulene administration group has improvement result to above-mentioned pathology damage, wherein the wide leaves of pulse plants of β-
Fragrant alkene high dose group (40mg/kg) effect is more apparent, and stomach lining keeps complete, and epithelium, which has no, to fall off, and body of gland has no damage, inherently
The rare bleeding of layer and cell infiltration (general comment is divided into 5.61 ± 0.71), other dosage have different degrees of protective effect, in
The overall score of dosage group and low dose group is respectively 6.39 ± 1.00 and 6.94 ± 0.93.
Almost without observing macroscopic damage in normal group.Compared with normal group, stomach-filling dehydrated alcohol can be shown
It writes and increases ulcer area, show that alcohol induced gastric ulcer model is successfully established.Under the action of Lansoprazole, ulcer area is aobvious
It writes and reduces, 21.24 ± 6.67mm of average out to2(inhibiting rate 85.47%).With β-patchoulene (10,20 Hes of various dose
After 40mg/kg) being administered, ulcer area is significantly reduced, and dose-dependent relationship is presented.In addition, dosage is the wide leaves of pulse plants of β-of 40mg/kg
Fragrant alkene group ulcer area minimum (11.48 ± 2.80mm2), inhibiting rate highest (92.19%).Dosage is the β-of 20 and 10mg/kg
In patchoulene group, ulcer area is respectively 15.76 ± 4.13 (being suppressed to 89.35%) and 17.27 ± 6.66mm2(inhibiting rate
For 88.22%).
Test example 3
The influence for the rat acute gastric ulcer model that this test example research β-patchoulene induces Indomethacin.
SPF grades of male SD rats are taken, weighs, is randomly divided into normal group (Intact), model group (Vehicle), Lan Suola
Azoles group (LSZ, 200mg/kg), β-patchoulene low, middle and high dose groups (corresponding β-Pogostemon cablin amount is 10,20,40mg/kg), often
Group 8.After grouping, label, then each rat body weight is weighed, record and calculate corresponding administered volume (1mL/100g).Except normal group
0.5%Tween-80 solution is given with model group, other, which are organized, gives corresponding drug therapy, daily gastric infusion 1 time, continuously
Administration 7 days.In 30 minutes after the last administration, every rat oral gavage Indomethacin (1mL/100g) caused acute gastric mucosal injury,
Rat needs fasting 24 hours before modeling, free water.After stomach-filling Indomethacin 5 hours, each rat euthanasia takes out full stomach,
Stomach wall is cut off along greater curvature, cleans gastric content, expansion gastric tissue is placed between two pieces of glass plates and fixes for taking pictures.With
ImageJ image analysis software (1.47v, National Institutes of Health, USA) calculates ulcer area, and counts
Calculate inhibiting rate.Inhibiting rate (%)=(model group ulcer area-administration group ulcer area)/model group ulcer area × 100%.
0.5cm × 0.5cm gastric tissue is taken in same area, is fixed on 4% paraformaldehyde solution, conventional film-making, hematoxylin-eosin dye
Color is observed and is taken pictures under microscope (OLYMPUS BX53 fluorescence microscope), and You Sanwei Pathology Doctors ' is using independent scoring.
Reference literature carries out the histology pathological score of stomach lining inflammation and degree of injury and calculates total score；Wherein, it scores
Standard is as shown in table 1.
Each data are indicated with mean ± standard deviation (mean ± SD), are charted using Graphpad Prism7 software, SPSS
20.0 softwares carry out statistical analysis, comparison in difference between each group, using one-way analysis of variance (One-Way ANOVA), variance
Qi Shi, Multiple range test uses LSD method two-by-two between group；When heterogeneity of variance, Multiple range test uses Dunnett ' s T3 method two-by-two between group,
It is standard with P < 0.05, indicates significant difference.Normal group is examined compared with model group using independent sample T
(Student's t test).Compared with normal group: #:P < 0.05, ##:P < 0.01；Compared with model group: *: P < 0.05, * *: P
<0.01。
Fig. 6 shows the influence of Indomethacin induced rat gastric ulcer area and inhibiting rate；Fig. 7 shows β-patchoulene
To the histological scores of Indomethacin induced rat acute gastric mucosal injury.
It was found from the result of this test example and Fig. 6, Fig. 7:
Almost without observing macroscopic damage in normal group.Compared with normal group, stomach-filling Indomethacin can be shown
It writes and increases ulcer area, show that the gastric ulcer model of Indomethacin induction is successfully established.Under the action of Lansoprazole, ulcer surface
Product substantially reduces, 6.39 ± 0.91mm of average out to2, inhibiting rate 84.29%.With β-patchoulene of various dose (10,20,
After 40mg/kg) being administered, ulcer area is significantly reduced, and dose-dependent relationship is presented.In addition, dosage is the wide leaves of pulse plants of β-of 40mg/kg
Fragrant alkene group ulcer area is 8.03 ± 0.86mm2, inhibiting rate 80.24%.Dosage is β-patchoulene group of 20 and 10mg/kg
In, ulcer area is respectively 10.13 ± 0.86 (being suppressed to 75.09%) and 18.74 ± 0.71mm2(inhibiting rate 53.85%).
Histological observation shows that rat normal gastric mucosa structural integrity, mucous membrane surface foveolae gastricae is high-visible, mucous membrane inner gland
The close rule of body arrangement, epithelium, which has no, to fall off, and body of gland has no damage, and lamina propria has no bleeding and cell infiltration；Model group stomach
Mucosa injury compared with depth and area it is larger, foveolae gastricae structure is destroyed, and oedema and inflammatory infiltration occurs, and a large amount of epithelial cells denaturation take off
It falls, erosion, gland structure disorder, some missings, lamina propria is shown in moderate bleeding (general comment is divided into 9.50 ± 0.72)；Lansoprazole group
Stomach lining is complete, and epithelium, which has no, to fall off, and body of gland has no damage, and lamina propria has no that (general comment is divided into 5.56 for bleeding and cell infiltration
±0.58)；β-patchoulene administration group has improvement result to above-mentioned pathology damage, wherein β-patchoulene high dose group
(40mg/kg) effect is more apparent, and stomach lining keeps complete, and epithelium, which has no, to fall off, and body of gland has no damage, the rare bleeding of lamina propria and
Cell infiltration (general comment is divided into 5.56 ± 0.81), other dosage have a different degrees of protective effect, middle dose group and low dose
The overall score of amount group is respectively 6.28 ± 077 and 6.72 ± 0.83.
Test example 4
The pharmaceutical composition that this test example studies the offer of embodiment 4- embodiment 8 imitates the treatment of acute gastric ulcer rat model
Fruit.
It is observed after acute gastric ulcer rat model is administered in the pharmaceutical composition that embodiment 4-8 is provided, finds energy
Enough cure acute gastric ulcer rat model.
The foregoing is only a preferred embodiment of the present invention, is not intended to restrict the invention, for the skill of this field
For art personnel, the invention may be variously modified and varied.All within the spirits and principles of the present invention, made any to repair
Change, equivalent replacement, improvement etc., should all be included in the protection scope of the present invention.
Claims (10)
1. a kind of application of pharmaceutical composition in preparation prevention and/or treatment acute gastric ulcer drug；It is characterized in that, described
The effective component of pharmaceutical composition includes β-patchoulene；
The preparation method of the β-patchoulene includes: that Patchoulicalcohol reacts in organic solvent with acid, is extracted with nonpolar solvent
Reaction product is taken, then by extract liquor chromatography post separation.
2. application according to claim 1, which is characterized in that the organic solvent is ethyl alcohol or methanol.
3. application according to claim 1, which is characterized in that the nonpolar solvent is n-hexane or petroleum ether.
4. application according to claim 1, which is characterized in that the extract liquor described in chromatography post separation includes by the extraction
Liquid is separated with silica gel column chromatography, is then separated with neutral aluminum oxide column chromatography.
5. application according to claim 4, which is characterized in that the packing material size of the silicagel column is 200~300 mesh；Institute
The packing material size for stating neutral alumina column is 200~300 mesh.
6. application according to claim 1, which is characterized in that the extract liquor described in chromatography post separation, using non-polar material
Matter elution.
7. application according to claim 1-6, which is characterized in that the acid is hydrochloric acid or sulfuric acid.
8. application according to claim 1-6, which is characterized in that described pharmaceutical composition further includes pharmaceutically may be used
The carrier or auxiliary material of receiving.
9. application according to claim 7, which is characterized in that described pharmaceutical composition further includes pharmaceutically acceptable load
Body or auxiliary material.
10. application of the β-patchoulene in preparation prevention and/or treatment acute gastric ulcer drug.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910603298.8A CN110151739A (en) | 2017-06-16 | 2017-06-16 | The application of β-patchoulene and the application including β-patchoulene pharmaceutical composition |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201910603298.8A CN110151739A (en) | 2017-06-16 | 2017-06-16 | The application of β-patchoulene and the application including β-patchoulene pharmaceutical composition |
| CN201710458440.5A CN107021867A (en) | 2017-06-16 | 2017-06-16 | A kind of preparation method, pharmaceutical composition and the application of β patchoulenes |
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| CN201710458440.5A Division CN107021867A (en) | 2017-06-16 | 2017-06-16 | A kind of preparation method, pharmaceutical composition and the application of β patchoulenes |
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| CN110151739A true CN110151739A (en) | 2019-08-23 |
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| CN201710458440.5A Pending CN107021867A (en) | 2017-06-16 | 2017-06-16 | A kind of preparation method, pharmaceutical composition and the application of β patchoulenes |
| CN201910603298.8A Pending CN110151739A (en) | 2017-06-16 | 2017-06-16 | The application of β-patchoulene and the application including β-patchoulene pharmaceutical composition |
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| CN108420805B (en) * | 2018-05-16 | 2021-01-15 | 东莞广州中医药大学中医药数理工程研究院 | Application of beta-patchouli alkene in preparation of medicine for preventing or treating male sexual dysfunction |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100166896A1 (en) * | 2008-12-30 | 2010-07-01 | Sterling International Inc. | Methods for repelling insects using sesquiterpene hydrocarbons and their derivatives |
| WO2010147309A2 (en) * | 2009-06-19 | 2010-12-23 | 삼일제약주식회사 | Pharmaceutical composition for preventing or treating inflammatory gastrointestinal disease comprising patchouli extract |
| CN102406886A (en) * | 2011-12-01 | 2012-04-11 | 西北农林科技大学 | Nanoemulsion compound transdermal spray for treating chronic gastritis and gastric ulcer |
-
2017
- 2017-06-16 CN CN201710458440.5A patent/CN107021867A/en active Pending
- 2017-06-16 CN CN201910603298.8A patent/CN110151739A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100166896A1 (en) * | 2008-12-30 | 2010-07-01 | Sterling International Inc. | Methods for repelling insects using sesquiterpene hydrocarbons and their derivatives |
| WO2010147309A2 (en) * | 2009-06-19 | 2010-12-23 | 삼일제약주식회사 | Pharmaceutical composition for preventing or treating inflammatory gastrointestinal disease comprising patchouli extract |
| CN102406886A (en) * | 2011-12-01 | 2012-04-11 | 西北农林科技大学 | Nanoemulsion compound transdermal spray for treating chronic gastritis and gastric ulcer |
Non-Patent Citations (3)
| Title |
|---|
| BÜCHI, G.等: "Terpenes. XVI. Constitution of Patchouli Alcohol and Absolute Configuration of Cedrene", 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》 * |
| ZHENG, YI-FENG ET AL.: "Gastroprotective effect and mechanism of patchouli alcohol against ethanol, indomethacin and stress-induced ulcer in rats", 《CHEMICO-BIOLOGICAL INTERACTIONS》 * |
| 陈晓盈: "β-广藿香烯抗炎作用及机制研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》 * |
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| CN107021867A (en) | 2017-08-08 |
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