CN106008248A - Celecoxib pharmaceutical composition and application thereof in biological medicine - Google Patents

Celecoxib pharmaceutical composition and application thereof in biological medicine Download PDF

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Publication number
CN106008248A
CN106008248A CN201610343221.8A CN201610343221A CN106008248A CN 106008248 A CN106008248 A CN 106008248A CN 201610343221 A CN201610343221 A CN 201610343221A CN 106008248 A CN106008248 A CN 106008248A
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compound
celecoxib
pharmaceutical composition
preparation
extract
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Inventor
秦勇
李波
牛绍雄
吴敏
周超
王声音
徐成
周自桂
王�琦
陈建芳
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JIANGSU SHENLONG PHARMACEUTICAL CO Ltd
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JIANGSU SHENLONG PHARMACEUTICAL CO Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
    • C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
    • C07C229/56—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in ortho-position
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
    • A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
    • A61K31/245—Amino benzoic acid types, e.g. procaine, novocaine
    • 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
    • A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
    • A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/38—Separation; Purification; Stabilisation; Use of additives

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Emergency Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses a celecoxib pharmaceutical composition and application thereof in biological medicine. The celecoxib pharmaceutical composition provided by the invention contains celecoxib and a natural product compound (I) with a novel structure; when the celecoxib and the compound (I) act independently, the celecoxib and the compound (I) have a treatment effect on immune thrombocytopenic purpura; when the celecoxib and the compound (I) act in a combined manner, the treatment effect on the immune thrombocytopenic purpura is remarkably improved; the celecoxib pharmaceutical composition can be developed into a medicament for treating the immune thrombocytopenic purpura; compared with the prior art, the celecoxib medicinal composition has outstanding substantial characteristics and remarkable progress.

Description

The pharmaceutical composition of celecoxib and the application in biological medicine thereof
Technical field
The invention belongs to biomedicine field, relate to the new application of celecoxib, be specifically related to the medicine group of celecoxib Compound and the application in biological medicine thereof.
Background technology
Celecoxib be clinically used for relief from osteoarthritis sings and symptoms, alleviate adult rheumatoid arthritis symptom and Sign, treatment adult acute's pain.
Celecoxib is nonsteroidal antiinflammatory drug, observes its effect having antiinflammatory, easing pain and bring down a fever in animal model.Plug The mechanism of action carrying out former times cloth is to suppress prostaglandin to generate by suppression Transitional cell carcinomas (COX-2).And it is dense at human body therapy Under degree, this product does not has inhibitory action to isozyme-Cycloxygenase-1 (COX-1).
In animal colon tumor model, celecoxib slow down generation and the progress of tumor.
Summary of the invention
It is an object of the invention to provide the pharmaceutical composition of a kind of celecoxib, this pharmaceutical composition carrys out former times containing plug Cloth and the natural product of a kind of novel structure, celecoxib and this natural product can be with Synergistic treatment immune thrombocytopenic Purpura.
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 celecoxib, including celecoxib, compound as claimed in claim 1 (I) and medicine Acceptable carrier on, 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: Fructus Liquidambaris is pulverized by (a), with 65～75% 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 9 column volumes of 20% ethanol elution, then with 10 column volumes of 65% ethanol elution, collects 65% and washes De-liquid, concentrating under reduced pressure obtains 65% ethanol elution concentrate；C in () step (b), 65% 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 65:1,35:1,15:1 and 7:1 successively；(d) step Suddenly in (c), component 4 separates further by purification on normal-phase silica gel, successively with the methylene chloride-methanol ladder that volume ratio is 12:1,7:1 and 1:1 Degree affords 3 components；E reverse phase silica gel that in () step (d), component 2 is bonded by octadecylsilane separates, with volume hundred Point concentration is the methanol aqueous solution isocratic elution of 58%, collects 11～15 column volume eluents, and eluent is concentrated under reduced pressure to give Compound (I).
Further, in the preparation method of compound (I), step (a) is extracted with 70% alcohol heat reflux, united extraction Liquid.
Further, in the preparation method of compound (I), described macroporous resin is D101 type macroporous adsorbent resin.
Further, in the preparation method of compound (I), step (a) replace ethyl acetate to extract with dichloromethane Take, obtain dichloromethane extract.
The above-claimed cpd (I) application in the medicine of preparation treatment immunologic thrombocytopenic purpura.
The pharmaceutical composition of above-mentioned celecoxib answering in the medicine of preparation treatment immunologic thrombocytopenic purpura With.
Advantages of the present invention: containing celecoxib and a kind of structure in the pharmaceutical composition of the celecoxib that the present invention provides Novel natural product, when celecoxib, compound (I) independent role, has treatment to immunologic thrombocytopenic purpura Effect；When celecoxib and compound (I) synergy, the therapeutic effect of immunologic thrombocytopenic purpura is significantly carried Height, can develop into the medicine for the treatment of immunologic thrombocytopenic purpura.
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.
Embodiment 1: compound (I) separates preparation and structural identification
Separation method: Fructus Liquidambaris (2kg) is pulverized by (a), extracts (15L × 3 time) with 70% 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 9 column volumes of 20% ethanol elution, then uses 65% ethanol elution 10 column volumes, collect 65% eluent, and concentrating under reduced pressure obtains 65% ethanol elution concentrate；C in () step (b), 65% ethanol is washed De-concentrate purification on normal-phase silica gel separates, successively with volume ratio be 65:1 (9 column volumes), 35:1 (10 column volumes), 15:1 (8 Individual column volume) and the methylene chloride-methanol gradient elution of 7:1 (8 column volumes) obtain 4 components；Component 4 in (d) step (c) Separate further by purification on normal-phase silica gel, successively with volume ratio be 12:1 (6 column volumes), 7:1 (7 column volumes) and 1:1 (6 posts Volume) methylene chloride-methanol gradient elution obtain 3 components；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 58%, collects 11～15 column volume eluting Liquid, eluent is concentrated under reduced pressure to give compound (I) (purity is more than 98%).
Structural identification: HR-ESI-MS shows [M+H]+For m/z 340.2196, can obtain molecular formula in conjunction with nuclear-magnetism feature is C22H29NO2, degree of unsaturation is 9.Hydrogen nuclear magnetic resonance modal data δH(ppm, CDCl3, 500MHz): H-2a (1.34, m), H-2b (1.68, m), H-3a (1.78, m), H-3b (2.25, m), H-5 (2.86, d, J=10.9Hz), H-6 (5.11, dt, J=10.2, 3.1Hz), H-7a (2.14, dd, J=13.2,2.7Hz), H-7b (2.43, br, t, J=12.3Hz), H-9 (5.53, br, t, J =6.5Hz), H-10a (1.84, m), H-10b (2.14, m), H-11 (1.87, s), H-13 (2.23, s), H-14 (2.27, s), H-15 (1.14, s), H-3 ' (6.69, dd, J=8.2,1.0Hz), H-4 ' (7.25, ddd, J=8.5,7.2,1.6Hz), H-5 ' (6.57, ddd, J=8.1,7.1,1.0Hz), H-6 ' (7.68, dd, J=8.0,1.6Hz)；Carbon-13 nmr spectra data δC (ppm, CDCl3, 125MHz): 43.7 (C, 1-C), 42.1 (CH2, 2-C), 33.5 (CH2, 3-C), 157.4 (C, 4-C), 52.3 (CH, 5-C), 71.6 (CH, 6-C), 42.2 (CH2, 7-C), 135.2 (C, 8-C), 124.8 (CH, 9-C), 41.8 (CH2, 10-C), 27.4(CH3, 11-C), 113.2 (C, 12-C), 19.9 (CH3, 13-C), 21.3 (CH3, 14-C), 20.8 (CH3, 15-C), 169.4 (C, C=O), 111.2 (C, 1 '-C), 153.4 (C, 2 '-C), 114.6 (CH, 3 '-C), 134.4 (CH, 4 '-C), 115.0 (CH, 5 '-C), 130.5 (CH, 6 '-C).IR spectrum shows that this compound contains amino (3482 and 3372cm-1) and ester carbonyl group (1678cm-1).The molecular formula that the high-resolution of this compound is given shows that this compound is the compound of a nitrogen atom, has 9 degrees of unsaturation.The hydrogen spectrum of compound shows that this compound has neighbour dibasic phenyl ring proton signal (δH6.69, 7.25,6.57 and 7.68), an olefinic methine proton signal (δH5.53), a company oxygen methine proton signal (δH5.11) And four unimodal methyl signals (δH1.87,2.23,2.27 and 1.14).The carbon spectrum of this compound shows that this compound has 22 Carbon signal, wherein has the carbon signal on ten olefinic carbon signals or phenyl ring, an ester carbonyl group carbon signal and company's oxygen carbon letter Number.Preliminary HSQC and HMBC spectrum resolves and finds, H-6 '/C-CO, H-6 '/C-2 ', H-4 '/C-2 ', H-5 '/C-3 ' and H- Being correlated with between 6 '/C-5 ' can connect neighbour's dibasic benzoyl signal.Remove 7 carbon of benzoyl, change Compound there remains 15 carbon signals, can be inferred that this compound is a sesquiterpenoids derivant with this.Consult pertinent literature Finding, this compound has similar structure, benzoyl ortho-substituent therein with known compound elaeochytrinA It it is an amino group.Relatively both nuclear magnetic resonance datas are it is found that noval chemical compound and elaeochytrin A's is unique How difference has been one group of double key carbon signal.Further HMBC spectrum resolves and finds, H-13/C-12, H-13/C-4, H- Dependency explanation double bond between 14/C-4 is in C-4 and C-12 position.So far, the plane of compound has resolved out, still It it is so a benzoyl substituted guainane type sesquiterpene.In ROESY spectrum, the dependency between H-15/H-6 illustrates benzene first Acyl group is in α position.Comprehensive hydrogen spectrum, carbon spectrum, HMBC spectrum and ROESY spectrum, and document is about correlation type nuclear magnetic data, can Substantially determining that this compound is as follows, spatial configuration is determined by ECD test further, theoretical value and experiment value basic Cause.
This compound chemical formula and carbon atoms numbered are as follows:
Embodiment 2: pharmacological action
The present embodiment uses by obtaining BALB/C mice platelet antibody, is inoculated into Cavia porcellus, obtains Cavia porcellus and resists little Mus platelet antibody (APS), sets up immunologic thrombocytopenic purpura animal model by APS lumbar injection BALB/C mice, Observe the anti-immune blood of the aspects such as medicine makes platelet count rise, Spleen coefficient reduces, bone marrow maturation megalokaryocyte increases Platelet minimizing property purpura effect.
1, materials and methods
1.1 animal
BALB/C mice, body weight 18～23g, male and female half and half, SPF level, purchased from medical animal experiment center, Guangdong Province；Globefish Mus, female, body weight 350g, regular grade, purchased from medical animal experiment center, Guangdong Province.
1.2 reagent and sample
Celecoxib is purchased from Nat'l Pharmaceutical & Biological Products Control Institute.Compound (I) is made by oneself, and preparation method is shown in embodiment 1.Not Family name's Freund's incomplete adjuvant (Beijing ancient cooking vessel Bioisystech Co., Ltd, DH-1341-1), (Tianjin BASF chemical industry is limited for EDTA-Na2 Company, analytical pure), Ethylurethanm (Guangdong Guanghua Science and Technology Co., Ltd., analytical pure), oxalic acid ammonia (Guangdong brilliance science and technology share Company limited, analytical pure), prednisone (northwest the second synthesis pharmaceutical factory, medicinal specification), Switzerland's staining reagent (Beijing Bo Run Lay Special Science and Technology Ltd.).
1.3 instrument
Automatic blood analyzer (method, ABXPENTRA60), (Sai Duolisi scientific instrument (Beijing) have electronic balance Limit company, BSA1245), thermostat water bath (Changzhou Ao Hua Instrument Ltd., HA-4), centrifugal precipitation mechanism (Asia, Shanghai Rong Shenghua Instrument plant, 80-2), Constant Temp. Oven (Guangzhou Kang Heng Instrument Ltd., 101-A), (Nikon instrument is limited for microscope Company, Nikoneclipsee100).
The 1.4 sero-fast preparations of Cavia porcellus antiplatelet
Taking the BALB/C mice of health to pluck eyeball and take blood, stand half an hour, 8000rpm/min is centrifuged 10min, takes upper strata Serum 1500rpm/min is centrifuged 15min, takes upper serum 900rpm/min and is centrifuged 10min, takes upper serum 3000rpm/min Centrifugal 10min, discards serum, obtains bottom precipitation platelet, adds 1% oxalic acid ammonia 1mL, stands 5min, 3000rpm/min centrifugal 10min, discards supernatant liquid, bottom platelet brine three times, with normal saline dilution to concentration be 1～2 × 109/ L, is mixed into Freund's complete adjuvant platelet antigen with Freund's complete adjuvant and incomplete Freund's adjuvant by 1:1 respectively and mixes Thing and not Freund's complete adjuvant platelet antigen mixture, standby；Take healthy guinea pig 10, help completely in the 1st week injection Freund Agent platelet antigen mixture is in its extremity, abdomen stock, back, subcutaneous, and often place's injection 100 μ L, in the same agent of injection in the 2nd, 3,4 weeks The not Freund's complete adjuvant platelet antigen mixture of amount.4th weekend with 20% urethane 2mL abdominal cavity depending on penetrating anaesthetized guinea pig, the heart The dirty blood that takes, 1500rpm/min is centrifuged 10min, takes upper serum, and remaining whole blood continues 3000rpm/min and is centrifuged 10min, merges Twice gained serum, obtains Cavia porcellus anti-mouse platelet serum APS, and-20 DEG C of preservations are standby.Self-control diameter 9cm agarose plate, Quincunx hole, interstitial hole dropping platelet suspension (500 × 10 is broken into card punch9/ L), holes around add 1:2,1:4,1:8,1: 16, the Cavia porcellus anti-mouse platelet serum of 1:32,1:64 difference titer.37 DEG C of incubation 24h, observe precipitation arc, and detection is anti- Serum titer.
Prepared by 1.5 mice group and model
Mice is randomly divided into 6 groups, often group 12, and respectively Normal group, model control group, positive controls is (strong Song Long group, 2.25mg kg-1) and celecoxib group (120mg kg-1), compound (I) group (120mg kg-1), celecoxib With compound (I) compositions group [60mg kg-1Celecoxib+60mg kg-1Compound (I)].Take out-20 DEG C of preservations APS, 56 DEG C of water-bath 30min inactivate complement, and by the titer of normal saline dilution to 1:4, mice carries out lumbar injection.In 0,2,4, 6,8,10d inject the antiserum of dilution according to 100 μ g/20g mouse peritoneals, every 2d duplicate injection once, to remain hematoblastic Persistently reduce.After the 1st injection APS, administration group presses above-mentioned corresponding dosage intraperitoneal injection, Normal group and model pair According to group injecting normal saline.
1.6 platelet count experiments
2h after being administered for 10th day, plucks eyeball and takes blood, detect platelet count.
1.7 Spleen coefficient determination experiments
Dissect and take out liver, weigh, calculate Spleen coefficient.
1.8 Megakaryocytic classification number determination experiments
Peel off femur, take out bone marrow smear, Switzerland's staining dyeing, calculate Megakaryocytic classification number
1.9 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 immunologic thrombocytopenic purpura model mice platelet count
Comparing with Normal group, model control group mouse platelets counting substantially reduces (P ＜ 0.01)；With model comparison Group compares, and celecoxib significantly raises (P ＜ 0.01) with compound (I) compositions group and positive controls platelet count；With Model control group compares, and celecoxib group, compound (I) group mouse platelets counting raises (P ＜ 0.05).The results are shown in Table 1.
2.2 impacts on immunologic thrombocytopenic purpura model mice Spleen coefficient
With Normal group ratio, the Spleen coefficient of model control group mice is significantly raised (P ＜ 0.01).With model control group Relatively, celecoxib significantly reduces (P ＜ 0.01) with compound (I) compositions group and positive controls mouse spleen coefficient；With Model control group compares, and celecoxib group, compound (I) group mouse spleen coefficient significantly reduces (P ＜ 0.05).The results are shown in Table 1.
2.3 impacts on immunologic thrombocytopenic purpura model mice macrophage
Comparing with Normal group, the full-brown macrophage number of model control group mice is decreased obviously (P ＜ 0.01).With mould Type matched group compares, and celecoxib writes with the full-brown macrophage digital display of compound (I) compositions group and positive controls mice Raise (P ＜ 0.01)；Comparing with model control group, the full-brown macrophage several litres of celecoxib group, compound (I) group mice is high (P ＜ 0.05).The results are shown in Table 1.
Table 1 is on immunologic thrombocytopenic purpura model mice platelet, Spleen coefficient and the impact of macrophage
Purpura is one of the most common bleeding, is owing to there is antiplatelet antibody in the patient.At present The inside and outside main first-line drug for the treatment of for purpura is hormone medicine such as prednisone, cortisone, prednisolone etc., or vein Injection human normal immunoglobulin and splenectomy etc..In terms of pharmacological point, hormone is used to carry out treatment mainly by suppressing blood The phagocytosis of platelet, the generation of suppression platelet antibody.The immune organs such as spleen are the main place producing platelet antibody, pass through Produce platelet antibody and destroy phagocytosis platelet, then excite complement system, outside knee joint blood vessel classical, non-classical, destroy blood little Plate, causes subcutaneous hemorrhage phenomenon.But according to clinical statistics, using hormone medicine treatment to have relapse rate high, side effect is many, and the course for the treatment of is long Etc. shortcoming, patient needs Long-term taking medicine to treat.According to statistics, only 10～20% do not have rebound phenomenon after patient's drug withdrawal.Use spleen Excision treatment, logical for intractable purpura is ineffective, is difficult to for a long time for Low patient, particularly elderly patient Heavy dose accepts the impact treatment of hormone medicine.
The above results shows, when celecoxib, compound (I) independent role, has immunologic thrombocytopenic purpura There is therapeutical effect；When celecoxib and compound (I) synergy, the therapeutic effect of immunologic thrombocytopenic purpura is shown Write and improve, the medicine for the treatment of immunologic thrombocytopenic purpura can be developed into.
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 (10)

1. a compound (I) with following structural formula,
2. the pharmaceutical composition of a celecoxib, it is characterised in that: include celecoxib, chemical combination as claimed in claim 1 Thing (I) and pharmaceutically acceptable carrier, be prepared as the dosage form needed.
The pharmaceutical composition of celecoxib the most according to claim 2, it is characterised in that: pharmaceutically acceptable carrier Including diluent, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carrier Or lubricant.
The pharmaceutical composition of celecoxib the most according to claim 2, it is characterised in that: described dosage form includes tablet, glue Wafer, oral liquid, suck agent, granule, electuary, pill, powder, unguentum, sublimed preparation, suspensoid, powder, solution, injection, 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 road Road is logical pulverizes, with 65～75% alcohol heat reflux extract, united extraction liquid, be concentrated into without alcohol taste, use petroleum ether, acetic acid second successively 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 9 column volumes of 20% ethanol elution, then uses 65% ethanol elution 10 column volumes, collect 65% eluent, and concentrating under reduced pressure obtains 65% ethanol elution concentrate；C in () step (b), 65% ethanol is washed De-concentrate purification on normal-phase silica gel separates, and washes by the methylene chloride-methanol gradient that volume ratio is 65:1,35:1,15:1 and 7:1 successively Take off and obtain 4 components；D in () step (c), component 4 separates further by purification on normal-phase silica gel, successively with volume ratio be 12:1,7:1 and The methylene chloride-methanol gradient elution of 1:1 obtains 3 components；In (e) step (d) component 2 with octadecylsilane be bonded anti- Phase silica gel separates, and with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 58%, collects 11～15 column volume eluents, 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: step (a) is returned by 70% ethanol heat Stream extracts, united extraction liquid.
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.
The preparation method of compound the most according to claim 5 (I), it is characterised in that: step (a) uses dichloromethane generation Extract for ethyl acetate, obtain dichloromethane extract.
9. the application in the medicine of preparation treatment immunologic thrombocytopenic purpura of the compound (I) described in claim 1.
10. the arbitrary described pharmaceutical composition of claim 2～4 is at the medicine of preparation treatment immunologic thrombocytopenic purpura In application.
CN201610343221.8A 2016-05-20 2016-05-20 Celecoxib pharmaceutical composition and application thereof in biological medicine Pending CN106008248A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
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
CN106083988A (en) * 2016-06-22 2016-11-09 陈露 The pharmaceutical composition of a kind of succimer and medical usage thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
RACHA ALKHATIB等: "Activity of elaeochytrin A from Ferula elaeochytris on leukemia cell lines", 《PHYTOCHEMISTRY》 *

Cited By (2)

* Cited by examiner, † Cited by third party
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
CN106083988A (en) * 2016-06-22 2016-11-09 陈露 The pharmaceutical composition of a kind of succimer and medical usage thereof

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