CN106117305A - The pharmaceutical composition of a kind of dioxopromethazine hydrochloride and medical usage thereof - Google Patents
The pharmaceutical composition of a kind of dioxopromethazine hydrochloride and medical usage thereof Download PDFInfo
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- CN106117305A CN106117305A CN201610493098.8A CN201610493098A CN106117305A CN 106117305 A CN106117305 A CN 106117305A CN 201610493098 A CN201610493098 A CN 201610493098A CN 106117305 A CN106117305 A CN 106117305A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
- C07J71/001—Oxiranes
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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
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/5415—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
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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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
- A61K31/585—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin containing lactone rings, e.g. oxandrolone, bufalin
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- Organic Chemistry (AREA)
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Abstract
The invention discloses pharmaceutical composition and the medical usage thereof of a kind of dioxopromethazine hydrochloride, containing dioxopromethazine hydrochloride and the natural product compound (I) of a kind of novel structure in the pharmaceutical composition of the dioxopromethazine hydrochloride that the present invention provides, when dioxopromethazine hydrochloride, compound (I) independent role, cholelithiasis had therapeutical effect；When dioxopromethazine hydrochloride and compound (I) synergy, the therapeutic effect of cholelithiasis is significantly improved, can be developed into the medicine for the treatment of cholelithiasis, compared with prior art there is prominent substantive distinguishing features and significantly progress.
Description
Technical field
The invention belongs to biomedicine field, relate to the new application of dioxopromethazine hydrochloride, be specifically related to dioxopromethazine hydrochloride
Pharmaceutical composition and treatment cholelithiasis in application.
Background technology
The hydrochloric acid of the entitled 10-of chemistry (2-dimethylamino-isopropyl) phenothiazine-5,5-dioxide of dioxopromethazine hydrochloride
Salt, have antitussive and relieving asthma, eliminate the phlegm, anti-cholamine and local anesthetic action, antitussive effect is relatively strong, suitable with codeine.It is clinically used for town
Cough, eliminate the phlegm, the cough caused for acute and chronic tracheitis and various disease.
Up to now, there is not yet the dependency report of dioxopromethazine hydrochloride and pharmaceutical composition thereof and treatment cholelithiasis.
Summary of the invention
It is an object of the invention to provide the pharmaceutical composition of a kind of dioxopromethazine hydrochloride, containing salt in this pharmaceutical composition
Acid dioxopromethazine and a kind of natural product, dioxopromethazine hydrochloride and this natural product can be with Synergistic treatment cholelithiasis.
The above-mentioned purpose of the present invention is achieved by techniques below scheme:
A kind of compound (I) with following structural formula,
The pharmaceutical composition of a kind of dioxopromethazine hydrochloride, including dioxopromethazine hydrochloride, compound as claimed in claim 1
(I) and pharmaceutically acceptable carrier, is prepared as the dosage form needed.
Further, pharmaceutically acceptable carrier include diluent, excipient, filler, binding agent, wetting agent,
Disintegrating agent, absorption enhancer, surfactant, absorption carrier or lubricant.
Further, described dosage form include tablet, capsule, oral liquid, suck agent, granule, electuary, pill, powder,
Unguentum, sublimed preparation, suspensoid, powder, solution, injection, suppository, spray, drop or patch.
The preparation method of above-claimed cpd (I), comprises following operating procedure: Folium Ilicis Cornutae is pulverized by (a), with 80～90% second
Alcohol circumfluence distillation, united extraction liquid, it is concentrated into without alcohol taste, successively by petroleum ether, ethyl acetate and water saturated n-butyl alcohol extraction
Take, respectively obtain petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol extract；B in () step (a), n-butyl alcohol takes thing use
Macroporous resin remove impurity, first with 6 column volumes of 30% ethanol elution, then with 12 column volumes of 85% ethanol elution, collects 85% and washes
De-liquid, concentrating under reduced pressure obtains 85% ethanol elution concentrate；C in () step (b), 85% ethanol elution concentrate purification on normal-phase silica gel is divided
From, obtain 4 components with the methylene chloride-methanol gradient elution that volume ratio is 100:1,50:1,25:1 and 12:1 successively；(d)
In step (c), component 4 separates further by purification on normal-phase silica gel, successively by dichloromethane-first that volume ratio is 20:1,12:1 and 2:1
Alcohol gradient elution obtains 3 components；E reverse phase silica gel that in () step (d), component 2 is bonded by octadecylsilane separates, and uses body
Long-pending percentage concentration is the methanol aqueous solution isocratic elution of 88%, collects 13～16 column volume eluents, eluent concentrating under reduced pressure
Obtain compound (I).
Further, in the preparation method of compound (I), described macroporous resin is D101 type macroporous adsorbent resin.
The above-claimed cpd (I) application in the medicine of preparation treatment cholelithiasis.
The application in the medicine of preparation treatment cholelithiasis of the pharmaceutical composition of above-mentioned dioxopromethazine hydrochloride.
Advantages of the present invention:
Containing dioxopromethazine hydrochloride and a kind of novel structure in the pharmaceutical composition of the dioxopromethazine hydrochloride that the present invention provides
Natural product, when dioxopromethazine hydrochloride, compound (I) independent role, cholelithiasis is had therapeutical effect；Dioxopromethazine hydrochloride
During with compound (I) synergy, the therapeutic effect of cholelithiasis is significantly improved, can be developed into the medicine for the treatment of cholelithiasis.
Detailed description of the invention
Further illustrate the essentiality content of the present invention below in conjunction with embodiment, but do not limit the present invention with this and protect model
Enclose.Although the present invention being explained in detail with reference to preferred embodiment, it will be understood by those within the art that, can be right
Technical scheme is modified or equivalent, without deviating from the spirit and scope of technical solution of the present invention.
Embodiment 1: compound (I) separates preparation and structural identification
Reagent source: ethanol, petroleum ether, ethyl acetate, n-butyl alcohol, dichloromethane are analytical pure, insults peaking purchased from Shanghai
Learning reagent company limited, methanol, analytical pure, purchased from Jiangsu Han Bang chemical reagent company limited.
Separation method: Folium Ilicis Cornutae (2kg) is pulverized by (a), extracts (15L × 3 time) with 85% alcohol heat reflux, united extraction
Liquid, is concentrated into without alcohol taste (3L), successively with petroleum ether (3L × 3 time), ethyl acetate (3L × 3 time) and water saturated n-butyl alcohol
(3L × 3 time) extract, and respectively obtain petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol extract；In (b) step (a)
Acetic acid ethyl ester extract D101 type macroporous resin remove impurity, first with 6 column volumes of 30% ethanol elution, then uses 85% ethanol elution
12 column volumes, collect 85% eluent, and concentrating under reduced pressure obtains 85% ethanol elution concentrate；C in () step (b), 85% ethanol is washed
De-concentrate purification on normal-phase silica gel separates, successively with volume ratio be 100:1 (12 column volumes), 50:1 (10 column volumes), 25:1
The methylene chloride-methanol gradient elution of (8 column volumes) and 12:1 (8 column volumes) obtains 4 components；Group in (d) step (c)
Points 4 separate further by purification on normal-phase silica gel, successively with volume ratio be 20:1 (6 column volumes), 12:1 (8 column volumes) and 2:1 (6
Individual column volume) methylene chloride-methanol gradient elution obtain 3 components；Component 2 octadecylsilane key in (e) step (d)
The reverse phase silica gel closed separates, and with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 88%, collects 13～16 column volumes
Eluent, eluent is concentrated under reduced pressure to give compound (I) (HPLC normalization purity is more than 98%).
Structural identification: HR-ESI-MS shows [M+H]+For m/z 465.2243, can obtain molecular formula in conjunction with nuclear-magnetism feature is
C28H32O6, degree of unsaturation is 13.Hydrogen nuclear magnetic resonance modal data δH(ppm, CDCl3, 500MHz): H-2 (2.22, ddd, J=
14.5,8.7,5.3Hz), and H-2 (2.64, ddd, J=14.5,9.7,6.3Hz), H-3 (1.88, m), H-3 (1.91, m), H-4
(1.23, m), H-4 (1.94, m), H-6 (3.12, br, s), H-7 (1.38, ddd, J=14.5,11.1,1.3Hz), H-7
(2.16, ddd, J=14.5,3.6,2.7Hz), H-8 (1.46, qd, J=11.1,3.6Hz), H-9 (2.28, dd, J=11.2,
4.1Hz), and H-11 (4.55, d, J=4.1Hz), H-14 (2.23, m), H-15 (2.02, m), H-15 (2.25, m), H-16
(5.54, m), H-18 (0.98, s), H-19 (1.05, s), H-20 (3.14, dd, J=11.1,7.0Hz), H-21 (9.62, d, J
=7.0Hz), and H-22 (4.28, dd, J=11.1,1.9Hz), H-23 (5.13, s), H-27 (1.77, s), H-28 (1.88, s)；
Carbon-13 nmr spectra data δC(ppm, CDCl3, 125MHz) and 215.2 (C, 1-C), 39.2 (CH2, 2-C), 17.4 (CH2, 3-C),
29.6(CH2, 4-C), 64.0 (C, 5-C), 60.2 (CH, 6-C), 30.8 (CH2, 7-C), 35.8 (CH, 8-C), 38.7 (CH, 9-
C), 52.7 (C, 10-C), 101.2 (CH, 11-C), 159.4 (C, 12-C), 50.7 (C, 13-C), 34.8 (CH, 14-C), 33.2
(CH2, 15-C), 121.4 (CH, 16-C), 149.6 (C, 17-C), 19.3 (CH3, 18-C), 17.2 (CH3, 19-C), 52.7 (CH,
20-C), 201.4 (CH, 21-C), 67.4 (CH, 22-C), 93.2 (CH, 23-C), 157.3 (C, 24-C), 123.8 (C, 25-C),
175.2 (C, 26-C), 8.4 (CH3, 27-C), 12.0 (CH3, 28-C).Infrared spectrum shows this compound (1749cm Han ester-1)
With ketone (1713cm-1), aldehyde radical (1665cm-1) group.13C-NMR, DEPT and hsqc spectrum show 28 carbon signals, including four
Individual methyl, five methylene, ten methine (three oxygen-containing carbon δC60.2,67.4,93.2, an aldehyde radical carbon δC201.4, two
Olefinic methine δC, and nine quaternary carbon (ester group carbon δ 101.2,121.4)C175.2, a ketone group δC215.2, three alkene
Carbon δC149.6,157.3,123.8, a company oxygen carbon δC64.0 and a company oxygen olefinic carbon δC159.4)；Function above structure is tied again
Close insatiable hunger sum and show that this compound is seven ring structures.1There are four methyl proton signal δ in H-NMR spectrum displayH0.98 (3H, s),
1.05 (3H, s), 1.77 (3H, s), 1.88 (3H, s)；Three company oxygen proton signal δH3.12 (1H, br, s, H-6), 4.28 (1H,
Dd, J=11.1,1.9Hz, H-22), 5.13 (1H, s, H-23)；Two olefinic methine proton signal δH4.55 (1H, d, J=
4.1Hz, H-11), 5.54 (1H, m, H-16).Hydrocarbon nuclear magnetic spectrogram also shows to exist a α, β-unsaturated lactone side chain structure
[comprise two alkene methyl δH-271.77 with δH-281.88, a company oxygen methine δH-235.13 (1H, s)；δC-26175.2 (C),
δC-24157.3 (C), δC-25123.8 (C), δC-2393.2 (CH), δC-2812.0(CH3), δC-278.4(CH3)]；By the ketone of C-12
After being connected as hemiacetal bridge with 22-OH, C-12 hydroxyl and C-11 hydrogen slough formation exocyclic double bond hexa-atomic hemiacetal ring [δH-224.28
(1H, dd, J=11.1,1.9Hz), δH-219.62 (3H, d, J=7.0Hz)；δC-2267.4 (CH), δC-12159.4 (C), δC- 17149.6 (C), δC-21201.4(CH)]；One 5 β, 6 beta epoxide structure [δH-63.12 (1H, br, s)；δC-564.0 (C), δC- 660.2(CH)]。13C-NMR and hsqc spectrum show a single ketone group carbon δC-1215.2 (C) and two methylene [δC- 239.2 with δH-22.22 (1H, ddd, J=14.5,8.7,5.3Hz) and 2.64 (1H, 2.64, ddd, J=14.5,9.7,6.3Hz)
There is coherent signal；δC-317.4 with δH-31.88 (1H, m) He 1.91 (m) there is coherent signal in 1H],1H-1H COSY spectrum shows
It is shown with-C (2) H2-C(3)H2-C(4)H2-fragment, HMBC analysis of spectrum understands H2-2 and H2-3 exist coherent signal with C-1, consult literary composition
Offer, contrast coherent signal, it is known that this compound is withanolide compound.Additionally, the 16-H of 17-OH with C-16 of C-17 sloughs
Form the double bond structure [δ in five-membered ringH-165.54 (1H, m)；δC-16121.4 (CH), δC-17149.6(C)]；C-21 position is aldehyde
Base, confirms link position [δ by the coherent signal of H-2 Yu C-20 in HMBC and H-20 Yu C-21H-219.62 (1H, d, J=
7.02Hz), δC-21201.4(CH)].Comprehensive hydrogen spectrum, carbon spectrum, HMBC spectrum and ROESY spectrum, and document is about correlation type nuclear-magnetism
Data, can determine that this compound is as follows substantially, and spatial configuration is determined by ECD test further, theoretical value and experiment value
Basically identical.
This compound chemical formula and carbon atoms numbered are as follows:
Embodiment 2: pharmacological action
The present embodiment uses lincomycin hydrochloride subcutaneous injection to prepare cholelithiasis guinea pig model, observes medicine and reduces cholelithiasis
Guinea-pig Gallbladder mucosa TGR5 positive expression rate, reduces the anti-cholelithiasis effect of the aspects such as gall-stone formation.
1, materials and methods
1.1 animal
Cavia porcellus, female, 350～450g, Lanzhou Inst. of Biological Products, Ministry of Public Health's Experimental Animal Center provide.
1.2 reagent and sample
Dioxopromethazine hydrochloride is purchased from Nat'l Pharmaceutical & Biological Products Control Institute.Compound (I) is made by oneself, and preparation method is shown in embodiment
1。
1.3 instrument
One anti-Rabbit Polyelonal to GPCR TGR5 (ab72608) (U.S. Abcam) and two resists, and is purchased from
Abcam and Beijing Bioisystech Co., Ltd of Zhong Shan Golden Bridge；OlympusDp72 image collecting analyzer (Olympus company of Japan
Produce).
Prepared by 1.4 Cavia porcellus packets and model
Cavia porcellus is randomly divided into 5 groups, often group 12, respectively Normal group, model control group, dioxopromethazine hydrochloride group
(80mg·kg-1), compound (I) group (80mg kg-1), dioxopromethazine hydrochloride and compound (I) compositions group [40mg kg-1
Dioxopromethazine hydrochloride+40mg kg-1Compound (I)].In addition to Normal group, other groups all give lincomycin hydrochloride 60mg/
Kg, 1 time/d, subcutaneous injection, inject 4d, drug withdrawal 2d continuously, then inject 3d and carry out modeling.It is raw that Normal group gives Isodose
Reason saline subcutaneous injection.According to above-mentioned dosage gastric infusion after modeling success, 1 time/d, totally 8 days；Model control group and the most right
Same dose of normal saline gavage is given according to group.
1.5 gallbladder volume determination experiments
Test the 12nd day, before last is administered, fasting 24h.After last is administered 1h, by Cavia porcellus with pentobarbital sodium 40mg/kg
Intraperitoneal injection of anesthesia, opens abdominal cavity, ligation cystic duct excision gallbladder, extracts bile out with empty needle, measure gallbladder volume [gallbladder volume
(μ l/g)=Amount of Bile (μ l)/Cavia porcellus weight (g)].
1.6 immunohistochemical observation positive cell experiments
Use the dyeing of Envision method.TGR5 repairs through citric acid high temperature, concrete operation step by specification.Take dyeing good
Good Cavia porcellus is respectively organized section and observes under an optical microscope and take a picture, and under microscope, each section randomly selects 10 visuals field,
Brown or tan homogenizing or granular material occur for positive cell criterion with gallbladder mucosa epithelial cell teleblem side.
1.7 statistical method
Experimental data mean ± standard deviation (x ± s) represents, application SPSS18.0 version statistical software carries out single factor test variance
Analyze and t checks, statistically significant for difference with P ＜ 0.05.
2, experimental result
2.1 impacts on cholelithiasis model guinea pigs gallbladder volume
Comparing with Normal group, model control group Guinea-pig Gallbladder volume substantially increases (P ＜ 0.01), shows modeling effect
Preferably；Comparing with model control group, dioxopromethazine hydrochloride and compound (I) compositions group Guinea-pig Gallbladder volume are substantially reduced (P ＜
0.01)；Comparing with model control group, dioxopromethazine hydrochloride group, compound (I) group Guinea-pig Gallbladder volume reduces (P ＜ 0.05).
Result of the test is shown in Table 1.
2.2 impacts on cholelithiasis model guinea pigs gallbladder mucosa TGR5 positive expression
Comparing with Normal group, the gallbladder mucosa TGR5 positive expression of model control group Cavia porcellus is remarkably reinforced (P ＜
0.01).Comparing with model control group, dioxopromethazine hydrochloride is positive with gallbladder mucosa TGR5 of compound (I) compositions group Cavia porcellus
Express and substantially weaken (P ＜ 0.01)；Comparing with model control group, the gallbladder of dioxopromethazine hydrochloride group, compound (I) group Cavia porcellus sticks
Film TGR5 positive expression weakens (P ＜ 0.05).The results are shown in Table 1.
Table 1 is on cholelithiasis model guinea pigs gallbladder volume and the impact of gallbladder mucosa TGR5 positive expression
| Group | Gallbladder volume (μ l/g) | Positive rate (%) |
| Normal group | 0.32±0.07 | 0 |
| Model control group | 1.13±0.18 | 100 |
| Dioxopromethazine hydrochloride group | 0.78±0.15 | 62 |
| Compound (I) group | 0.84±0.15 | 57 |
| Dioxopromethazine hydrochloride and compound (I) compositions group | 0.56±0.14 | 11 |
TGR5 (Gpbarl) is a kind of transmembrane G protein coupling Farnesoid X receptor being similar to rhodopsin, is 7 cross-film fat eggs
In vain, receptor ectodomain (N-end) identification extracellular signaling molecule is the most in combination, intracellular domain (C-end) and G-protein
Coupling.By with G-protein coupling, regulate related enzyme activity, intracellular generation second message,second messenger, thus by extracellular signal cross-film pass
It is delivered to intracellular.The protein expression of TGR5mRNA finds, including Mus in many different human tissues and rodent tissue
Bile duct epithelial cell and gall bladder epithelial cells.Research finds that TGR5 is positioned human gall bladder mucosal epithelial cells teleblem side and bile duct
On epithelial cell fibril hair, and the expression of GS patient gallbladder TGR5 is apparently higher than matched group.
Most advanced and sophisticated sodium dependency cholate carrier (ASBT) of TGR5 mediation promotes the outer bile acid counter transport of born of the same parents, makes the bile of intracellular
Acid concentration raises, and inhibits bile acid biosynthesis key enzyme in hepatocyte-cholesterol 7a mono-hydroxylase (cytochrome to feedback
P450, family7, subfamily A, polypeptide1；Cyp7al), make bile acid biosynthesis reduce and cholesterol increases, row
Enter biliary tract and form cholesterol supersaturation cause stone bile.
When dioxopromethazine hydrochloride, compound (I) independent role, cholelithiasis had therapeutical effect；Dioxopromethazine hydrochloride and
During compound (I) synergy, the therapeutic effect of cholelithiasis is significantly improved, can be developed into the medicine for the treatment of cholelithiasis.
The effect of above-described embodiment indicates that the essentiality content of the present invention, but does not limit the protection of the present invention with this
Scope.It will be understood by those within the art that, technical scheme can be modified or equivalent,
Essence and protection domain without deviating from technical solution of the present invention.
Claims (8)
1. a compound (I) with following structural formula,
2. the pharmaceutical composition of a dioxopromethazine hydrochloride, it is characterised in that: include dioxopromethazine hydrochloride, such as claim 1 institute
The compound (I) stated and pharmaceutically acceptable carrier, be prepared as the dosage form needed.
The pharmaceutical composition of dioxopromethazine hydrochloride the most according to claim 2, it is characterised in that: pharmaceutically acceptable
Carrier includes diluent, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption
Carrier or lubricant.
The pharmaceutical composition of dioxopromethazine hydrochloride the most according to claim 2, it is characterised in that: described dosage form includes sheet
Agent, capsule, oral liquid, suck agent, granule, electuary, pill, powder, unguentum, sublimed preparation, suspensoid, powder, solution, note
Penetrate agent, suppository, spray, drop or patch.
5. the preparation method of the compound (I) described in claim 1, it is characterised in that comprise following operating procedure: (a) is by Chinese holly
Bone leaf pulverize, with 80～90% alcohol heat reflux extract, united extraction liquid, be concentrated into without alcohol taste, successively use petroleum ether, acetic acid second
Ester and water saturated n-butanol extraction, respectively obtain petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol extract；(b)
In step (a), n-butyl alcohol takes thing macroporous resin remove impurity, first with 6 column volumes of 30% ethanol elution, then uses 85% ethanol elution
12 column volumes, collect 85% eluent, and concentrating under reduced pressure obtains 85% ethanol elution concentrate；C in () step (b), 85% ethanol is washed
De-concentrate purification on normal-phase silica gel separates, successively by the methylene chloride-methanol gradient that volume ratio is 100:1,50:1,25:1 and 12:1
Afford 4 components；D in () step (c), component 4 separates further by purification on normal-phase silica gel, be 20:1,12:1 by volume ratio successively
3 components are obtained with the methylene chloride-methanol gradient elution of 2:1；E in () step (d), component 2 is bonded by octadecylsilane
Reverse phase silica gel separates, and with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 88%, collects 13～16 column volume eluting
Liquid, eluent is concentrated under reduced pressure to give compound (I).
The preparation method of compound the most according to claim 5 (I), it is characterised in that: described macroporous resin is D101 type
Macroporous adsorbent resin.
7. the application in the medicine of preparation treatment cholelithiasis of the compound (I) described in claim 1.
8. the pharmaceutical composition of the arbitrary described dioxopromethazine hydrochloride of claim 2～4 is in the medicine of preparation treatment cholelithiasis
Application.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105924413A (en) * | 2016-05-20 | 2016-09-07 | 江苏神龙药业有限公司 | Celecoxib drug composition and medical application of composition in cholelithiasis treatment |
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| CN102260317A (en) * | 2011-08-08 | 2011-11-30 | 南京泽朗医药科技有限公司 | Method for extracting withanolide |
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2016
- 2016-06-24 CN CN201610493098.8A patent/CN106117305A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102260317A (en) * | 2011-08-08 | 2011-11-30 | 南京泽朗医药科技有限公司 | Method for extracting withanolide |
Non-Patent Citations (1)
| Title |
|---|
| HUAPING ZHANG ET AL.: "Withanolides fromJaborosa caulescens var.bipinnatifida", 《PHYTOCHEMISTRY》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105924413A (en) * | 2016-05-20 | 2016-09-07 | 江苏神龙药业有限公司 | Celecoxib drug composition and medical application of composition in cholelithiasis treatment |
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