CN106588827A - Extraction method and application of hypericum monogynum extract for treating ulcerative colitis - Google Patents
Extraction method and application of hypericum monogynum extract for treating ulcerative colitis Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
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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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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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)
Abstract
The invention provides an active pharmaceutical ingredient which is extracted from hypericum monogynum and used for treating ulcerative colitis. The active pharmaceutical ingredient can strengthen a shielding guaranteeing effect of a colonic mucous membrane, reduce the mucocutaneous lymph node bacterium displacement rate, prevent shortening of a colon, and improve the curative effect of the ulcerative colitis.
Description
Technical field
The present invention relates to natural drug extractive technique field, more particularly to a kind of gold for treating ulcerative colitiss
Silk crab apple extract.
Background technology
Ulcerative colitiss belong to a kind of nonspecific inflammatory enteropathy, and clinical manifestation is mainly mucus bloody purulent stool, diarrhoea, abdomen
Pain pain, tenesmus and different degrees of General Symptomies etc., pathological changes primary limitation is distributed in colorectal mucosa and Submucosa.Should
Sick protracted course of disease, clinic there is no the method for radical cure, induce and maintain clinical remission, treat complication, improve patients ' life quality be
Current clinical treatment target.Clinically for the disease is mainly with immunobiologic agent, probiotic bacteria, immunosuppressant, sugared cortical hormone
The Therapeutic Method such as element, alleviate conditions of patients, improve patients ' life quality etc..
Replace phloroglucinol derivatives compound (PPAPs) containing natural multi-ring many isopentene groups in hypericum, belong to
Hypericin, the parent nucleus of this structure is phloroglucinol, generally by benzoyl, isobutyryl or 2- Metliyl-butyyls and many
Individual isopentene group replaces.The multiformity of structure is made causes such compound to have various biological activity, including antibiotic property, antiinflammatory
The nervous system effect such as property, antiviral, antidepressant.In recent years PPAP classes compound has become natural product chemistry and correlation
One new study hotspot in field.
Xu Gang of Kunming Inst. of Botany, Chinese Academy of Sciences etc. is extracted from spoon calyx Radix Hyperici Monogyni (Herba Hyperici Monogyni) (Guttiferae Hypericum)
12 kinds of bicyclic many isopentene groups replace phloroglucinol derivatives compound (BPPAs), and various monocyclic isophthalic three are extracted from Herba Hyperici Patuli
Phenolic compound, and it was found that these monocyclic phloroglucinol derivatives compounds have antineoplastic activity.
The spun gold Caulis et folium euphorbiae milii in Shandong Laoshan region is also a common kind in Guttiferae Hypericum, and the applicant is led to
Cross research to find, it also replaces phloroglucinol derivatives compound (BPPAs) containing various bicyclic many isopentene groups.Due to this class
Compound has functions that excellent anti-inflammation, and applicant is separated by extracting, and obtains between two kinds of bicyclic many isopentene groups replacements
Benzenetriol class compound (BPPAs) a, stepping of going forward side by side action thing pharmaceutically active detection, finds the bicyclic many isopentene groups of one of which
Replace phloroglucinol derivatives compound that there are significant curative effect, clinic popularization and application in terms for the treatment of ulcerative colitiss.
The content of the invention
The technical problem to be solved be to provide a kind of extract in Caulis et folium euphorbiae milii from spun gold natural extract medicine into
Point, the composition can strengthen mucous membrane of colon shielding guaranteeing role, reduce film lymph node antibacterial transport ratio, prevent colon from shortening, and change
Kind ulcerative colitiss curative effect.
To solve above-mentioned technical problem, the invention provides a kind of active constituents of medicine is preparing treatment ulcerative colitiss
Medicine in application, its structural formula is：
Wherein, the active constituents of medicine is extracted from spun gold Caulis et folium euphorbiae milii.
Present invention also offers the extracting method of the active constituents of medicine of above-mentioned treatment ulcerative colitiss, it includes,
The first step, the root and leaf portion point of depletion silk Caulis et folium euphorbiae milii, pulverizes, and mixes；
Second step, the mixture 15kg for taking first step acquisition is soaked 4 times using methanol, and every time immersion 24 hours, make every time
It is 10L with quantity of methyl alcohol, the soak of 4 times is filtered, merged, and using Rotary Evaporators solvent is removed, and the concentration for obtaining 3.3kg is produced
Thing, enriched product is liquid；
3rd step, by enriched product into 4 parts, the silica gel mixing of the quality such as per part of use is further revolved on a rotary evaporator
Turn to evaporate being partly dissolved for remnants, obtain solid-state thing to be filtered, be ground into powder, upper silicagel column carries out coarse filtration using chloroform,
And obtain bicyclic many isopentene groups and replace phloroglucinol derivatives compound (BPPAs) 319.8g
4th step, the product that the 3rd step is obtained adopts liquid chromatograph post separation, eluent to adopt methanol percent by volume
80% methanol aqueous solution, isolates 4 kinds of different crude products, respectively the first crude product 41.1g, the second crude product 56.3g, the
Three crude product 35.7g, the 4th crude product 39.2g；
5th step, the eluent that silica column purification, employing is adopted to the second crude product is respectively ether/ethyl acetate volume
Mixed solution than 1: 2, the mixed solution and pure ethyl acetate of ether/ethyl acetate volume ratio 1: 1 isolate 6 kinds of thick products
Thing, respectively the first crude product 8.1g, the second crude product 5.5g, the 3rd crude product 16.3g, the 4th crude product 7.2g, the 5th is thick
Product 6.6g, the 6th crude product 3.1g；
6th step, to the 3rd crude product that the 5th step is obtained sephadex column Sephadex-LH20 purification, eluting are adopted
Liquid carries out eluting using chloroform/methanol volume ratio 1: 1 as eluent, obtains four kinds of crude products, respectively the first crude product
3.5g, the second crude product 2.9g, the 3rd crude product 2.7g, the 4th crude product 1.8g；
7th step, for the first crude product that the 6th step is obtained further carries out purification using silicagel column, what is adopted washes
De- liquid is respectively petrol ether/ethyl acetate volume ratio 100: 1, petrol ether/ethyl acetate volume ratio 50: 1, petroleum ether/acetic acid second
Ester volume ratio 10: 1, petrol ether/ethyl acetate volume ratio 2: 1, petrol ether/ethyl acetate volume ratio 1: 1, pure ethyl acetate, point
Two kinds of products are separated out, the first product quality is 217mg, and the second product quality 151mg, first product is exactly that the treatment is burst
The active constituents of medicine of ulcer colitis.
Present invention also offers a kind of endo-medicine for treating ulcerative colitiss, it includes the chemical combination shown in formula 1
Thing as active constituents of medicine and pharmaceutically acceptable carrier and excipient,
Mass percent of the active constituents of medicine in whole medicine is 10%～20%, preferably 10%～15%.
The endo-medicine can be prepared into various regular dosage forms using customary preparation methods.
Wherein described endo-medicine prepares piece agent, capsule, pill and oral liquid.
The present invention also provides a kind of tablet for treating ulcerative colitiss, and it includes compound, the crystallite shown in formula 1
Cellulose, starch, magnesium stearate,
Wherein, the mass percent of each material composition is the compound 10%～20% shown in formula 1, Microcrystalline Cellulose 40%
～80%, starch 30%～50%, magnesium stearate 1%～3%, each material composition quality sum is 100%.
Present invention also offers the preparation method of above-mentioned tablet, specially weighs by weight each raw material, mix, fill
Divide and stir 20 minutes, granule is uniformly obtained, tabletting obtains tablet.
Beneficial effects of the present invention：
The present invention extracts natural extract ingredient from spun gold Caulis et folium euphorbiae milii, and the composition can strengthen mucous membrane of colon shielding to be protected
Barrier is acted on, and reduces film lymph node antibacterial transport ratio, prevents colon from shortening, and improves ulcerative colitiss curative effect.
Specific embodiment
The invention provides a kind of active constituents of medicine for treating ulcerative colitiss, it is carried from spun gold Caulis et folium euphorbiae milii
Take out.
The extracting method of the medicine of the treatment ulcerative colitiss is specifically included,
The first step, the root and leaf portion point of depletion silk Caulis et folium euphorbiae milii, pulverizes, and mixes；
Second step, the mixture 15kg for taking first step acquisition is soaked 4 times using methanol, and every time immersion 24 hours, make every time
It is 10L with quantity of methyl alcohol, the soak of 4 times is filtered, merged, and using Rotary Evaporators solvent is removed, and the concentration for obtaining 3.3kg is produced
Thing, enriched product is liquid；
3rd step, by enriched product into 4 parts, the silica gel mixing of the quality such as per part of use is further revolved on a rotary evaporator
Turn to evaporate being partly dissolved for remnants, obtain solid-state thing to be filtered, be ground into powder, upper silicagel column is carried out slightly using chloroform
Filter, and obtain bicyclic many isopentene groups and replace phloroglucinol derivatives compound (BPPAs) 319.8g
4th step, the product that the 3rd step is obtained adopts liquid chromatograph post separation, eluent to adopt methanol percent by volume
80% methanol aqueous solution, isolates 4 kinds of different crude products, respectively the first crude product 41.1g, the second crude product 56.3g, the
Three crude product 35.7g, the 4th crude product 39.2g；
5th step, the eluent that silica column purification, employing is adopted to the second crude product is respectively ether/ethyl acetate volume
Mixed solution than 1: 2, the mixed solution and pure ethyl acetate of ether/ethyl acetate volume ratio 1: 1 isolate 6 kinds of thick products
Thing, respectively the first crude product 8.1g, the second crude product 5.5g, the 3rd crude product 16.3g, the 4th crude product 7.2g, the 5th is thick
Product 6.6g, the 6th crude product 3.1g；
6th step, to the 3rd crude product that the 5th step is obtained sephadex column Sephadex-LH20 purification, eluting are adopted
Liquid carries out eluting using chloroform/methanol volume ratio 1: 1 as eluent, obtains four kinds of crude products, respectively the first crude product
3.5g, the second crude product 2.9g, the 3rd crude product 2.7g, the 4th crude product 1.8g；
7th step, for the first crude product that the 6th step is obtained further carries out purification using silicagel column, what is adopted washes
De- liquid is respectively petrol ether/ethyl acetate volume ratio 100: 1, petrol ether/ethyl acetate volume ratio 50: 1, petroleum ether/acetic acid second
Ester volume ratio 10: 1, petrol ether/ethyl acetate volume ratio 2: 1, petrol ether/ethyl acetate volume ratio 1: 1, pure ethyl acetate, point
Two kinds of products are separated out, the first product quality is 217mg, and the second product quality 151mg, first product is exactly to treat exedens
The active constituents of medicine of colitis.
Present invention also offers application of the compound shown in formula 1 in the medicine for preparing treatment ulcerative colitiss.
The present invention also provides the endo-medicine for treating ulcerative colitiss, and it includes the compound conduct shown in formula 1
Active constituents of medicine and pharmaceutically acceptable carrier and excipient.
Mass percent of the active constituents of medicine in whole medicine is 10%～20%, preferably 10%～15%.
The endo-medicine can be prepared into various regular dosage forms using customary preparation methods, be preferably prepared to tablet, glue
Wafer, pill, oral liquid, most preferably prepare piece agent.
The present invention also provides a kind of tablet for treating ulcerative colitiss, and it includes compound, the crystallite shown in formula 1
Cellulose, starch, magnesium stearate, the mass percent of each material composition is the compound 10%～20% shown in formula 1, and crystallite is fine
Dimension element 40%～80%, starch 30%～50%, magnesium stearate 1%～3%, each material composition quality sum is 100%.
Present invention also offers the preparation method of above-mentioned tablet, specially weighs by weight each raw material, mix, fill
Divide and stir 20 minutes, granule is uniformly obtained, tabletting obtains tablet.
Embodiments of the present invention are described in detail using embodiment below, whereby to the present invention how application technology means
To solve technical problem, and reach technique effect realize that process can fully understand and implement according to this.
The extraction of the spun gold Caulis et folium euphorbiae milii of embodiment 1
The root and leaf portion of depletion silk Caulis et folium euphorbiae milii point, pulverizes, and mixes, and the mixture 15kg for taking acquisition is soaked using methanol
4 times, every time immersion 24 hours, are every time 10L using quantity of methyl alcohol, and the soak of 4 times is filtered, merged, removed using Rotary Evaporators
Remove solvent, obtain the enriched product of 3.3kg, enriched product is liquid, by enriched product into 4 parts, the silica gel of the quality such as per part of use
Mixing, further on a rotary evaporator rotation evaporates being partly dissolved for remnants, obtains solid-state thing to be filtered, is ground into powder,
Upper silicagel column, using chloroform coarse filtration is carried out, and obtains bicyclic many isopentene group replacement phloroglucinol derivatives compounds
(BPPAs) 319.8g, adopts liquid chromatograph post separation, eluent to adopt the first of methanol percent by volume 80% product for obtaining
Alcohol-water solution, isolates 4 kinds of different crude products, respectively the first crude product 41.1g, the second crude product 56.3g, the 3rd crude product
35.7g, the 4th crude product 39.2g, the eluent that silica column purification, employing is adopted to the second crude product is respectively ether/acetic acid
The mixed solution of ethyl ester volume ratio 1: 2, the mixed solution and pure ethyl acetate of ether/ethyl acetate volume ratio 1: 1, isolates
6 kinds of crude products, respectively the first crude product 8.1g, the second crude product 5.5g, the 3rd crude product 16.3g, the 4th crude product 7.2g,
5th crude product 6.6g, the 6th crude product 3.1g, the 3rd crude product to obtaining herein adopts sephadex column Sephadex-
LH20 purification, eluent carries out eluting using chloroform/methanol volume ratio 1: 1 as eluent, obtains four kinds of crude products, respectively
First crude product 3.5g, the second crude product 2.9g, the 3rd crude product 2.7g, the 4th crude product 1.8g, for for obtaining herein
One crude product further carries out purification using silicagel column, and the eluent for being adopted is respectively petrol ether/ethyl acetate volume ratio 100
: 1, petrol ether/ethyl acetate volume ratio 50: 1, petrol ether/ethyl acetate volume ratio 10: 1, petrol ether/ethyl acetate volume ratio 2
: 1, petrol ether/ethyl acetate volume ratio 1: 1, pure ethyl acetate isolates two kinds of products, and the first product is the thing shown in formula 1
Matter, quality is 217mg, and the second product is the material shown in formula 2, and quality 151mg, first product is exactly to treat exedens knot
The active constituents of medicine of enteritis.
First product adopts CDCl shown in formula 13Nmr analysis are carried out as solvent.
1H NMR(CDCl3, 600MHz)：δ 5.72 (1H, d)；5.64 (1H, m)；5.08 (1H, brs)；4.92 (1H, t)；
4.71 (1H, t)；4.49 (1H, s)；2.94 (1H, m)；2.64 (1H, m)；2.59 (1H, sept)；2.51 (1H, dd)；2.25
(1H, m)；2.19 (1H, m)；2.16 (1H, m)；2.05 (1H, m)；1.82 (1H, m)；1.75 (3H, s)；1.65 (12H, s)；
1.58 (2H, overlap)；1.54 (1H, m)；1.54 (3H, s)；1.38 (3H, s)；1.37 (3H, s)；1.13 (3H, s)；1.10
(3H, d)；0.97 (3H, d)；0.91 (2H, t).
Second product adopts CDCl shown in formula 23Nmr analysis are carried out as solvent.
1H NMR(CDCl3, 600MHz)：δ 5.72 (1H, d)；5.61 (1H, m)；5.07 (1H, brs)；4.92 (1H, t)；
4.71 (1H, t)；4.47 (1H, s)；2.97 (1H, dd)；2.62 (1H, dd)；2.51 (1H, dd)；2.42 (1H, m)；2.30 (2H,
m)；2.15 (1H, m)；2.07 (1H, overlap)；1.83 (1H, m)；1.75 (3H, s)；1.70 (2H, m)；1.64 (12H, s)；
1.60 (2H, overlap)；1.60 (3H, s)；1.57 (1H, m)；1.37 (3H, s)；1.37 (3H, s)；1.31 (3H, s)；1.13
(3H, s)；0.95 (3H, d)；0.97 (3H, d).
Pharmacodynamic experiment
Laboratory animal：100 male mices, between body weight 20g～24g, by Qingdao City's laboratory animal and zoopery
The heart is provided.
Experimental agents：Trinitro-benzene-sulfonic acid (TNBS), Sigma companies provide.
Packet and model：100 mices are randomly divided into normal group, model group, 1 group for the treatment of, treatment 2 groups and matched group, often
Group 20.
Modeling method, in addition to normal group, after remaining 4 groups of fasting 24 hours, etherization plugs in the silica gel tube of diameter 2mm
Enter mouse Colon to anus 8cm, (it is 30% that 20mgTNBS is dissolved in determining alcohol to the ethanol solution of configuration trinitro-benzene-sulfonic acid
In ethanol solution), using the ethanol solution coloclysis of the 0.5ml trinitro-benzene-sulfonic acid, after coloclysis terminate, make animal lie low, retain
20 minutes, regain consciousness naturally, free diet.In addition to normal group, in modeling 4 group 3 days, there is diarrhoea, mucus pus and blood in all animals
After an action of the bowels, modeling success.
Medication
Compound 1 shown in formula 1 and compound 2 shown in formula 2 are dissolved in respectively in distilled water and are configured to aqueous solution, per 1ml
The compound 1 dissolved in solution and the quality of compound 2 are 35mg, and 4 DEG C are stored in standby in refrigerator, 1ml/d coloclysis, matched group
Sulfasalazine is given, specification 250mg/ piece grinds, and with distilled water suspension is configured to, and is administered according to 0.3g/kg, 1ml/d
Coloclysis, model group gives isopyknic 0.9% chloride injection coloclysis, is within equal 10 days 1 course for the treatment of.
Observation index
The general status of animal, colon lengths and mass change during observation modeling
On 11st, cervical dislocation put to death each group mice, and dissociate colon, takes out whole colon, with pre-cooling it is aseptic 0.9%
Sodium chloride injection is clean by colonic irrigation, observes and record the substantially change of each group's mouse Colon, measures whole colon
Length.
With reference to disease activity index (DAI) standards of grading, weight, fecal character and the (connection of occulting blood of mice are observed daily
Aniline process is determined) situation, and record scoring.
The DAI standards of grading of table 1
| Score | Weight declines (%) | Stool | Stool blood |
| 0 | ＜ 1 | Amount less, firmly, it is dry, do not stick, do not dissipate | Without color |
| 1 | 1～5 | Amount less, it is hard, wet, glutinous | Color reaction is point-like |
| 2 | 6～10 | Amount is many, soft, very glutinous | Continue blueness |
| 3 | 11～15 | Amount is many, soft, scattered | Dark color is defecated+occults blood blueness |
| 4 | ＞ 15 | Loose stool | Hemafecia+dark blue reaction |
Note：DAI=(weight declines fraction+stool fraction+fraction of having blood in stool)/3
Each group mice mesenteric lymph node bacterial translocation rate
Clip universal mesentery lymph node, weighs and be homogenized respectively after quality, and each 0.1ml of tissue homogenate is trained in plain agar
Cultivated in 37 DEG C of incubators after 24h using painting bacterium method on foster base, according to diluting colonies count multiples bacterium colony number, (per g, tissue contains
Bacterium amount), represented with colony-forming units (CFU), every part of specimen does double culture.Calculating antibacterial transport ratio, antibacterial transport ratio=
Positive bacterial culture number of elements/total the number of elements of culture.
Statistical method
Calculating analysis is carried out using the statistics softwares of SPSS 16.0, measurement data adopts mean ± standard deviation Table
Show, multigroup mean compares and adopt one factor analysis of variance, P ＜ 0.05 are that difference is statistically significant.
As a result
Each group mice general status compare
During experiment, normal group mice hair color gloss, defecation is normal, and spirit is gamboled, and 2 groups of model group and treatment are from modeling
3d starts that lethargy is depressed, and fur is loosely matt, and appetite is reduced, and is had loose bowels, and hemafecia, form is become thin, and body weight is reduced, feed
Reduce, motion frequency is reduced.Matched group, 1 group for the treatment of are identical with model group symptom before the treatment, after treatment, matched group hemafecia number
Amount is reduced, molding of defecating, but DeGrain, and the complete molding of 1 group of stool for the treatment of, hemafecia quantity does not almost have, weight
Mitigate not substantially, general status are better than model group, matched group, 2 groups for the treatment of.
The scoring of each group DAI is compared, and the results are shown in Table 2.
± Δ is compared in the scoring of each group DAI of table 2
| Group | n | DAI scores |
| Treat 1 group | 20 | 1.09±0.13*Δ |
| Treat 2 groups | 20 | 3.61±0.25 |
| Model group | 20 | 3.92±0.28 |
| Normal group | 20 | 0.41±0.10 |
| Matched group | 20 | 1.57±0.30* |
Compare with model group,*P ＜ 0.01；Compare with matched group,ΔP ＜ 0.05.
By the result of table 2,1 group of the treatment and matched group disease activity index using the compound 1 of present invention extraction
Scoring is compared with 2 groups of model group and treatment, and difference is statistically significant, P ＜ 0.01, and compared with matched group, difference has for 1 group for the treatment of
Statistical significance, P ＜ 0.05, it is seen that the compound 1 that the present invention is extracted is significantly improved to ulcerative colitiss tool.
Each group mouse Colon length and mass change compare, and the results are shown in Table 3.
The each group mouse Colon length of table 3 and mass change compare
Compare with model group,*P ＜ 0.01；Compare with matched group,ΔP ＜ 0.05.
The colon lengths that can be seen that each group mice after trinitro-benzene-sulfonic acid (TNBS) coloclysis by the result of table 3 are equal
There is different degrees of shortening, and after treatment, 1 group for the treatment of, matched group colon lengths and model group, 2 groups of significant differences for the treatment of,
P ＜ 0.01, and treating 1 group and matched group more also has more significant difference, P ＜ 0.05, each group difference is not in colon quality
Significantly, and from terms of length with mass ratio, 1 group for the treatment of, matched group and model group, 2 groups of significant differences for the treatment of, P ＜ 0.01.It can be seen that
The compound 1 that the present invention is extracted can prevent colon from shortening.
Each group mice mesenteric lymph node antibacterial transport ratio, the results are shown in Table 4.
The each group mice mesenteric lymph node antibacterial transport ratio of table 4 compares
| Group | N | Antibacterial transport ratio (%) |
| Treat 1 group | 20 | 3*Δ |
| Treat 2 groups | 20 | 69 |
| Model group | 20 | 77 |
| Normal group | 20 | 0 |
| Matched group | 20 | 43* |
Compare with model group,*P ＜ 0.01；Compare with matched group,ΔP ＜ 0.05.
As can be known from the results of Table 4, the mesenteric lymph node antibacterial transport ratio of model group is significantly higher than normal group and treatment 1
Group, with model group difference less, 1 group for the treatment of difference and normal group between does not show 2 groups of mesenteric lymph node antibacterial transport ratios for the treatment of
Write, illustrating the medicine of present invention offer can strengthen mucous membrane of colon shielding guaranteeing role.
All above-mentioned this intellectual properties of primarily enforcement, setting limits this new product of enforcement of other forms
And/or new method.Those skilled in the art will be using this important information, the above modification, to realize similar execution feelings
Condition.But, all modifications or transformation are based on the right that new product of the present invention belongs to reservation.
The above, is only presently preferred embodiments of the present invention, is not the restriction for making other forms to the present invention, is appointed
What those skilled in the art changed possibly also with the technology contents of the disclosure above or be modified as equivalent variations etc.
Effect embodiment.But it is every without departing from technical solution of the present invention content, according to the technical spirit of the present invention to above example institute
Any simple modification, equivalent variations and the remodeling made, still falls within the protection domain of technical solution of the present invention.
Claims (10)
1. a kind of extracting method of the active constituents of medicine for treating ulcerative colitiss, it is characterised in that：The pharmaceutically active into
Divide and extracted from spun gold Caulis et folium euphorbiae milii,
The structural formula of the active constituents of medicine is
2. the extracting method of the active constituents of medicine of ulcerative colitiss is treated as claimed in claim 1, it is characterised in that bag
Include：
The first step, the root and leaf portion point of depletion silk Caulis et folium euphorbiae milii, pulverizes, and mixes；
Second step, the mixture 15kg for taking first step acquisition is soaked 4 times using methanol, every time immersion 24 hours, every time using first
Alcohol amount is 10L, and the soak of 4 times is filtered, merged, and using Rotary Evaporators solvent is removed, and obtains the enriched product of 3.3kg, dense
Contracting product is liquid；
3rd step, by enriched product into 4 parts, the silica gel mixing of the quality such as per part of use, further on a rotary evaporator rotation is steamed
Fall being partly dissolved for remnants, obtain solid-state thing to be filtered, be ground into powder, upper silicagel column carries out coarse filtration using chloroform,
And obtain bicyclic many isopentene groups and replace phloroglucinol derivatives compound (BPPAs) 319.8g
4th step, the product that the 3rd step is obtained adopts liquid chromatograph post separation, and eluent is using methanol percent by volume 80%
Methanol aqueous solution, isolates 4 kinds of different crude products, and respectively the first crude product 41.1g, the second crude product 56.3g, the 3rd are slightly produced
Thing 35.7g, the 4th crude product 39.2g；
5th step, adopts silica column purification to the second crude product, and the eluent of employing is respectively ether/ethyl acetate volume ratio 1:
2 mixed solution, the mixed solution and pure ethyl acetate of ether/ethyl acetate volume ratio 1: 1 isolate 6 kinds of crude products, point
Not Wei the first crude product 8.1g, the second crude product 5.5g, the 3rd crude product 16.3g, the 4th crude product 7.2g, the 5th crude product
6.6g, the 6th crude product 3.1g；
6th step, adopts sephadex column Sephadex-LH20 purification, eluent to adopt the 3rd crude product that the 5th step is obtained
Eluting is carried out with chloroform/methanol volume ratio 1: 1 as eluent, obtain four kinds of crude products, respectively the first crude product 3.5g, the
Two crude product 2.9g, the 3rd crude product 2.7g, the 4th crude product 1.8g；
7th step, for the first crude product that the 6th step is obtained further carries out purification using silicagel column, the eluent for being adopted
It is respectively petrol ether/ethyl acetate volume ratio 100: 1, petrol ether/ethyl acetate volume ratio 50: 1, petrol ether/ethyl acetate body
Product compares 10: 1, and petrol ether/ethyl acetate volume ratio 2: 1, petrol ether/ethyl acetate volume ratio 1: 1, pure ethyl acetate is isolated
Two kinds of products, the first product quality is 217mg, and the second product quality 151mg, first product is exactly that the treatment is exedens
The active constituents of medicine of colitis.
3. the active constituents of medicine for being extracted using extracting method described in claim 1 or 2 is preparing treatment ulcerative colitiss
Application in medicine.
4. a kind of endo-medicine for treating ulcerative colitiss, it is characterised in that：Including the compound shown in formula 1 as medicine
Thing active component and pharmaceutically acceptable carrier and excipient,
5. endo-medicine as claimed in claim 4, it is characterised in that：Quality hundred of the active constituents of medicine in whole medicine
Divide than being 10%～20%.
6. take orally as described in claim 4 or 5 and require, it is characterised in that：The endo-medicine can adopt customary preparation methods
It is prepared into various regular dosage forms.
7. take orally as described in claim 4 to 6 and require, it is characterised in that：The endo-medicine prepares piece agent, capsule, ball
Agent and oral liquid.
8. a kind of tablet for treating ulcerative colitiss, it is characterised in that：Including the compound shown in formula 1, microcrystalline cellulose
Element, starch, magnesium stearate,
9. tablet as claimed in claim 8, it is characterised in that：The mass percent of each material composition is the compound shown in formula 1
10%～20%, Microcrystalline Cellulose 40%～80%, starch 30%～50%, magnesium stearate 1%～3%, each material composition matter
Amount sum is 100%.
10. the preparation method of tablet described in claim 8 or 9, it is characterised in that：Each raw material is specially weighed by weight, is mixed
Together, stir 20 minutes, granule is uniformly obtained, tabletting obtains tablet.
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| CN201611241273.0A CN106588827B (en) | 2016-12-29 | 2016-12-29 | For treating the extracting method and application of the spun gold crab apple extract of ulcerative colitis |
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| CN201611241273.0A CN106588827B (en) | 2016-12-29 | 2016-12-29 | For treating the extracting method and application of the spun gold crab apple extract of ulcerative colitis |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110025629A (en) * | 2019-05-23 | 2019-07-19 | 河南大学 | Application of the hall crabapple flower flower polysaccharide in terms of preparing medicament for immunity enhancement |
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| US20020031560A1 (en) * | 1995-09-29 | 2002-03-14 | Dr. Willmar Schwabe Gmbh & Co. | Stable extract of hypercium perforatum L., processes for its preparation and pharmaceutical compositions |
| CN104744422A (en) * | 2014-11-21 | 2015-07-01 | 华中科技大学 | Compound with antitumor and anti-HIV (human immunodeficiency virus) activities in hypericum sampsonii hance as well as separation preparation and application of compound |
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2016
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| US20020031560A1 (en) * | 1995-09-29 | 2002-03-14 | Dr. Willmar Schwabe Gmbh & Co. | Stable extract of hypercium perforatum L., processes for its preparation and pharmaceutical compositions |
| CN104744422A (en) * | 2014-11-21 | 2015-07-01 | 华中科技大学 | Compound with antitumor and anti-HIV (human immunodeficiency virus) activities in hypericum sampsonii hance as well as separation preparation and application of compound |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110025629A (en) * | 2019-05-23 | 2019-07-19 | 河南大学 | Application of the hall crabapple flower flower polysaccharide in terms of preparing medicament for immunity enhancement |
| CN110025629B (en) * | 2019-05-23 | 2021-03-26 | 河南大学 | Application of filamental flowering crab polysaccharide in preparing immunity enhancing medicine |
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| Publication number | Publication date |
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| CN106588827B (en) | 2019-03-08 |
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