CN106496242A - The pharmaceutical composition of Latamoxef Sodium and its application in biological medicine - Google Patents
The pharmaceutical composition of Latamoxef Sodium and its application in biological medicine Download PDFInfo
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- CN106496242A CN106496242A CN201610818166.3A CN201610818166A CN106496242A CN 106496242 A CN106496242 A CN 106496242A CN 201610818166 A CN201610818166 A CN 201610818166A CN 106496242 A CN106496242 A CN 106496242A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
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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
- A61K31/535—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 oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5365—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 oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with heterocyclic ring systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/10—Spiro-condensed systems
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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)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/888—Araceae (Arum family), e.g. caladium, calla lily or skunk cabbage
- A61K36/8888—Pinellia
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- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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Abstract
The invention discloses the pharmaceutical composition of Latamoxef Sodium and its application in biological medicine, containing the natural products compound (I) that Latamoxef Sodium and a kind of structure are novel in the pharmaceutical composition of the Latamoxef Sodium that the present invention is provided, when Latamoxef Sodium, compound (I) independent role, there is therapeutic action to mRNA IN ADRIAMYCIN NEPHROPATHY syndrome；When Latamoxef Sodium and compound (I) synergy, the therapeutic effect of mRNA IN ADRIAMYCIN NEPHROPATHY syndrome is significantly improved, the medicine for the treatment of mRNA IN ADRIAMYCIN NEPHROPATHY syndrome can be developed into, has prominent substantive distinguishing features progressive with significant compared with prior art.
Description
Technical field
The invention belongs to biomedicine field, is related to the new application of Latamoxef Sodium, and in particular to the medicine of Latamoxef Sodium
Compositions and its application in biological medicine.
Background technology
The antimicrobial spectrum of Latamoxef Sodium is approximate with CTX, has good antibacterial action to multiple gram-negative bacterias.Greatly
Enterobacteria, Bacillus influenzae, klebsiella bacillus, various proteus, Enterobacter, citrobacter, serratia marcecens etc. are often to this
Product are extremely sensitive.There is good antibacterial action to anaerobic bacteria.Further, since the performance of the resistance to beta-lactamase of the product is strong, micro- life
Seldom there is drug resistance to the product in thing.
Content of the invention
It is an object of the invention to provide a kind of pharmaceutical composition of Latamoxef Sodium, containing drawing oxygen in the pharmaceutical composition
The novel natural products of cefonicid sodium and a kind of structure, Latamoxef Sodium and the natural products can be comprehensive with Synergistic treatment mRNA IN ADRIAMYCIN NEPHROPATHY
Simulator sickness.
The above-mentioned purpose of the present invention is achieved by techniques below scheme：
A kind of compound (I) with following structural formula,
A kind of pharmaceutical composition of Latamoxef Sodium, including Latamoxef Sodium, compound as claimed in claim 1 (I)
Pharmaceutically acceptable carrier, is prepared into the formulation of needs.
Further, pharmaceutically acceptable carrier include diluent, excipient, filler, adhesive, wetting agent,
Disintegrant, sorbefacient, surfactant, absorption carrier or lubricant.
Further, the formulation include tablet, capsule, oral liquid, mouth containing agent, granule, electuary, pill, powder,
Paste, sublimed preparation, supensoid agent, pulvis, solution, injection, suppository, spray, drops or patch.
The preparation method of above-claimed cpd (I), comprising following operating procedure：A the tuber of pinellia is crushed by (), with 65～75% ethanol
Circumfluence distillation, merges extract, is concentrated into without alcohol taste, uses petroleum ether, ethyl acetate and water saturated extracting n-butyl alcohol successively,
Respectively obtain petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol extract；B in () step (a), n-butanol takes thing with greatly
Hole resin removal of impurities, first with 20% ethanol elution, 9 column volumes, then with 65% ethanol elution, 10 column volumes, collects 65% and elutes
Liquid, reduced pressure concentration obtain 65% ethanol elution concentrate；C in () step (b), 65% ethanol elution concentrate is separated with purification on normal-phase silica gel,
It is 65 to use volume ratio successively:1、35:1、15:1 and 7:1 methylene chloride-methanol gradient elution obtains 4 components；(d) step
C in (), component 4 is further separated with purification on normal-phase silica gel, it is 12 to use volume ratio successively:1、7:1 and 1:1 methylene chloride-methanol gradient
Afford 3 components；The e octadecylsilane of component 2 is bonded in () step (d) reverse phase silica gel is separated, and uses volume basis
Concentration is 58% methanol aqueous solution isocratic elution, collects 11～15 column volume eluents, being concentrated under reduced pressure to give of eluent
Compound (I).
Further, in the preparation method of compound (I), step (a) is extracted with 70% alcohol heat reflux, is merged and is extracted
Liquid.
Further, in the preparation method of compound (I), the macroreticular resin is D101 type macroporous absorbent resins.
Further, in the preparation method of compound (I), in step (a), ethyl acetate is replaced to be extracted with dichloromethane
Take, obtain dichloromethane extract.
Application of the above-claimed cpd (I) in the medicine for preparing treatment mRNA IN ADRIAMYCIN NEPHROPATHY syndrome.
Application of the pharmaceutical composition of above-mentioned Latamoxef Sodium in the medicine for preparing treatment mRNA IN ADRIAMYCIN NEPHROPATHY syndrome.
Advantages of the present invention：Containing Latamoxef Sodium and one kind in the pharmaceutical composition of the Latamoxef Sodium that the present invention is provided
The novel natural products of structure, when Latamoxef Sodium, compound (I) independent role, has treatment to mRNA IN ADRIAMYCIN NEPHROPATHY syndrome
Effect；When Latamoxef Sodium and compound (I) synergy, the therapeutic effect of mRNA IN ADRIAMYCIN NEPHROPATHY syndrome is significantly improved, can
To develop into the medicine for the treatment of mRNA IN ADRIAMYCIN NEPHROPATHY syndrome.
Specific embodiment
With reference to the essentiality content that embodiment further illustrates the present invention, but present invention protection model is not limited with this
Enclose.
Embodiment 1：Compound (I) is separated and is prepared and structural identification
Separation method：A the tuber of pinellia (2kg) is crushed by (), extract (15L × 3 time) with 70% alcohol heat reflux, is merged and is extracted
Liquid, is concentrated into without alcohol taste (3L), uses petroleum ether (3L × 3 time), ethyl acetate (3L × 3 time) and water saturated n-butanol successively
(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 macroreticular resin removal of impurities, first with 20% ethanol elution, 9 column volumes, then uses 65% ethanol elution
10 column volumes, collect 65% eluent, and reduced pressure concentration obtains 65% ethanol elution concentrate；C in () step (b), 65% ethanol is washed
De- concentrate is separated with purification on normal-phase silica gel, and it is 65 to use volume ratio successively:1 (9 column volumes), 35:1 (10 column volumes), 15:1(8
Individual column volume) and 7:The methylene chloride-methanol gradient elution of 1 (8 column volumes) obtains 4 components；Component 4 in (d) step (c)
Further separated with purification on normal-phase silica gel, it is 12 to use volume ratio successively: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), the octadecylsilane of component 2 is bonded
Reverse phase silica gel is separated, and with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 58%, collects 11～15 column volume wash-outs
Liquid, eluent are concentrated under reduced pressure to give compound (I) (purity is more than 98%).
Structural identification：HR-ESI-MS shows [M+Na]+For m/z 301.1244, can obtain molecular formula in conjunction with nuclear-magnetism feature is
C15H18O5, degree of unsaturation is 7.Hydrogen nuclear magnetic resonance modal data δH(ppm, CD3OD, 500MHz)：H-1 α (1.52, m), H-1 β
(1.18, m), H-2 (1.68, m, 2H), H-3 α (1.82, m), H-3 β (1.28, m), H-5 (2.18, s), H-9 α (1.51, d, J=
13.8Hz), H-9 β (2.22, d, J=13.8Hz), H-13 (1.93, s), H-14 (1.11, s), H-15a (3.12, d, J=
11.8Hz), H-15b (2.81, d, J=11.8Hz)；Carbon-13 nmr spectra data δC(ppm, CD3OD, 125MHz)：41.1(CH2,
1-C), 20.3 (CH2, 2-C), 35.4 (CH2, 3-C), 61.9 (C, 4-C), 54.8 (CH, 5-C), 218.3 (C, 6-C), 148.7
(C, 7-C), 113.2 (C, 8-C), 51.2 (CH2, 9-C), 37.6 (C, 10-C), 121.5 (C, 11-C), 171.7 (C, 12-C),
8.5(CH3, 13-C), 18.2 (CH3, 14-C), 51.8 (CH2, 15-C).Hydrogen spectrum and carbon spectrum show that the compound contains a α, β-
Unsaturated gamma lactone structure [δC148.7 (C-7), 113.2 (C-8), 121.5 (C-11) and 171.7 (C-12)], one and half contractings
Aldehyde carbon [δC113.2 (C-8)], a vinyl methyl [δH1.93 (3H, s, H-13)；δC8.5 (C-13)], a methyl proton
Signal [δH1.11 (3H, s, H-14)；δC18.2 (C-14)] and a 1,1- substituted epoxy ethane structure [δH3.12 (1H, d, J
=11.8Hz, H-15a) and 2.81 (1H, d, J=11.8Hz, H-15b)；δC51.8 (C-15) and 61.9 (C-4)].In HMBC spectrums
H2- 15 and C-3, C-4 and C-5 correlation show oxirane be located between C-4 and C-15.In conjunction with nuclear magnetic data information and
High resolution mass spectrum information can be seen that this compound is typical eudesmane type sesquiterpene lactone compound.Consulting literatures are sent out
Now, the compound and known compound multistalactone A have similar structure, by being compared with the compound
It was found that, many ketone carbonyl carbon signals in noval chemical compound.Is found in the parsing that the HMBC of the compound is composed, H-5 is related to C-6
Property explanation in noval chemical compound additional carbonyl carbon signals base be positioned at C-6 positions.In ROESY spectrums, Me-14 and H-9 α, Me-
14 and H2- 15, and the correlation of H-9 β and H-5 shows H2- 15 and Me-14 is α configurations, and H-5 is beta comfiguration.Comprehensive hydrogen spectrum, carbon
Spectrum, HMBC spectrums and ROESY spectrums, and document is with regard to correlation type nuclear magnetic data, can determine substantially that the compound is as follows, stands
By ECD tests, body configuration further determines that theoretical value is basically identical with experiment value.
The compound chemical formula and carbon atoms numbered are as follows：
Embodiment 2：Pharmacological action
The present embodiment uses adriamycin (14.5mg kg-1) by osmotic pumps perfusion requirement filling, operation is implanted into rat abdominal cavity,
Adriamycin is released by osmotic pressure perseverance and induces nephrotic syndrome model preparation mRNA IN ADRIAMYCIN NEPHROPATHY syndrome (NS) rat model, observe medicine
Thing reduces NS rat Urine proteins, reduces the adriamycin ephrosis synthesis of the aspects such as rat blood serum urea nitrogen (BUN), creatinine (SCr)
The effect of levying.
1st, materials and methods
1.1 animal
SPF level SD rats, male, 180～200g of body weight, purchased from Guangdong Medical Lab Animal Center.All rats are equal
Action is active, hair luster, twice Urine proteins qualitative test feminine gender (test strips method).
1.2 reagent and sample
Latamoxef Sodium is purchased from Nat'l Pharmaceutical ＆ Biological Products Control Institute.Compound (I) is made by oneself, and preparation method is shown in embodiment 1.
ADMh (Wanle Pharmaceutical Co Ltd, Shenzhen), sodium chloride (Guangdong Zong Hua chemical drugs Co., Ltd., Factory), chloraldurate (Tianjin
Jinnan District salt water buys industrial park), multinomial urine detection test strips (Dry chemistry) (Ai Kang bio tech ltd) examines
Mas bright blue kit (builds up Science and Technology Ltd. in Nanjing), and (Beijing Bo Aosen is biological for FITC fluoresceins mark rabbit-anti rat IgG
Science and Technology Ltd.).
1.3 instrument
ALZET2004 type osmotic sustained release pumps (DURECT companies of the U.S.), metabolic cage (Suzhou City's Chinese mugwort Kelin animal used as test equipment
Factory), T6 new century ultraviolet-visible spectrophotometers (Beijing Puxi General Instrument Co., Ltd), T1000 type electronic balances
(Shuan Jie testers factory of Changshu City), EL204 type electronic analytical balances (Mettler-Toledo Instrument (Shanghai) Co., Ltd.),
65-12manul animal non-invasive blood pressure testers (IITC companies of the U.S.), automatic clinical chemistry analyzer (Hitachi -7180)；Frost is cut
Piece machine (LeicaCM1800)；Fluorescence inverted microscope (NIKONTE2000-S).
Prepared by the packet of 1.4 rats and model
1.4.1 preparation Alzet2004D osmotic pumps (0.25 ± 5) μ L h of adriamycin osmotic pumps-1, 28d).Claim before filling
Take each osmotic pumps quality and record, by osmotic pumps filling requirement filling adriamycin normal saline solution (14.5mg kg-1), weigh
Each osmotic pumps quality record after perfusion, with the mathematic interpolation perfusion volume of osmotic pumps quality before and after perfusion, perfusion volume is less than
Packing volume 90% is required, evacuation is refilled；The qualified saturating pump of filling is immersed in 37 DEG C of SPSSs, standby.
1.4.2 the implantation SD rats 60 of osmotic pumps, male, adaptability nursing 1 week, select 50 rats at random with 10%
Chloral hydrate anesthesia, rat back are fixed upward, 2cm positions opening adriamycin osmotic pumps are implanted on kidney below the right kidney
Side, suture muscle layer and cortex, postoperative every mouse intramuscular injection penicillin 0.2mL/ is only；Other 10, same operation is only inserted and is oozed
The onesize plastic cement of saturating pump, sham-operation are disposed as blank control group.Modeling situation is monitored with albustix during modeling, is made
After mould two weeks, 24h urines are collected, Coomassie Brilliant Blue determines urine protein content, and modeling group and normal group compare giving for indifference
To reject, modeling success rat is randomly divided into blank control group, model control group, positive controls (Dexamethasone group, 50mg
kg-1) and Latamoxef Sodium group (80mg kg-1), compound (I) group (80mg kg-1), Latamoxef Sodium and compound (I) group
Compound group【40mg·kg-1Latamoxef Sodium+40mg kg-1Compound (I)】.Adapt to environment after 1 week, continuous gavage is administered 7d,
Blank control group and the physiological saline of model control group rat ig equivalent.
1.5 24h Urine proteins determination experiments
Each group rat is loaded metabolic cage after being administered 4 weeks and collects 24h urines, Coomassie Brilliant Blue quantitative determination 24h urine eggs
Bai Liang, the Urine proteins change of observation each group rat.
1.6 Serum Indexes determination experiments
1h after last dose, anesthetized rat, abdominal aortic blood separate serum, and automatic clinical chemistry analyzer detects blood
Biochemical indicator：Urea nitrogen (BUN) and creatinine (Cr).
1.7 statistical method
Experimental data represents that with mean ± standard deviation (x ± s) application SPSS18.0 versions statistical software carries out single factor test variance
Analysis and t are checked, statistically significant as difference with P ＜ 0.05.
2nd, experimental result
The impact of the 2.1 pairs of NS rat models to NS Urine proteins
Compare with blank control group, model control group rat 24h Urine proteins significantly raise (P ＜ 0.01)；With model comparison
Group compares, and Latamoxef Sodium significantly reduces (P ＜ 0.01) with compound (I) composition group and positive controls Urine proteins；With mould
Type control group compares, and Latamoxef Sodium group, compound (I) group Urine proteins reduce (P ＜ 0.05).The results are shown in Table 1.
The impact of 2.2 pairs of NS rat model renal function index
With blank control group ratio, model control group rat BUN, Cr levels substantially rise (P ＜ 0.01).With model control group
Than Latamoxef Sodium is decreased obviously (P ＜ 0.01) with compound (I) composition group and positive controls rat BUN, Cr levels；
With model control group ratio, Latamoxef Sodium group, compound (I) group rat BUN, Cr levels decline (P ＜ 0.05).
Experimental result is shown in Table 1.
Impact of the table 1 to NS rat models Urine proteins and renal function index
| Group | Urine proteins mg | BUN/mmol·L-1 | SCr/μmol·L-1 |
| Blank control group | 7.44±1.66 | 7.35±0.76 | 23.26±2.37 |
| Model control group | 109.86±9.65 | 16.2±1.15 | 46.2±2.27 |
| Positive controls | 19.77±5.14 | 7.91±0.74 | 20.29±2.53 |
| Latamoxef Sodium group | 51.45±4.46 | 8.86±0.59 | 22.74±2.76 |
| Compound (I) group | 49.51±7.41 | 8.73±0.82 | 23.37±1.84 |
| Latamoxef Sodium and compound (I) composition group | 29.18±3.91 | 7.92±0.56 | 20.93±0.32 |
It is local segmenfcal nephritis, membranous nephropathy and minute lesion that the common Histopathology of nephrotic syndrome changes, closely
Over year, in adult nephrotic syndrome, MCNS and film productive nephritis are in minimizing trend, and mesentery IgA kidneys
Disease is in increase trend.Adriamycin induction adriamycin-induced nephropathy in Wistar rats syndrome is a classical model, the effect of adriamycin relevant enzyme in vivo
Under, cell membrane and organelle biomembrane lipid peroxidation is made, direct toxic action is produced to glomerulus and renal tubular epithelial and is produced
Raw High-grade Proteinuria.
Osmotic pressure slow-releasing pump technology is a kind of new constant speed sustained-release administration mode, by medicine, osmotic pressure agent and pellicle
Lasting on request for required reagent solution, quantitative fixed point sustained release is arrived by composition, the driving force for providing insoluble drug release by osmotic pressure
Need the position of administration.Osmotic pumps are implanted in animal used as test body and are administered (such as spinal cord, cranial cavity, liver, spleen for privileged site
Deng), successfully transported hundreds of medicament, including protein, polypeptide, growth factor, antibiotic, chemotherapeutic, hormone, steroids,
siRNA.Irreplaceable effect is played in various fields such as animal administration, animal model structure, drug screenings.This experiment is adopted
Adriamycin induction nephrotic syndrome model is released with micro- pump technology perseverance of oozing, and adriamycin is loaded micro- oozing and rat abdominal cavity is implanted in pump,
Carry out the micro release of long-term constant speed to adriamycin, extend adriamycin action time in animal body, it is to avoid because injection causes
Fluctuation of concentration.
The above results show, when Latamoxef Sodium, compound (I) independent role, mRNA IN ADRIAMYCIN NEPHROPATHY syndrome is had and is controlled
Treatment is acted on；When Latamoxef Sodium and compound (I) synergy, the therapeutic effect of mRNA IN ADRIAMYCIN NEPHROPATHY syndrome is significantly improved,
The medicine for the treatment of mRNA IN ADRIAMYCIN NEPHROPATHY syndrome 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 kind of compound (I) with following structural formula,
2. a kind of pharmaceutical composition of Latamoxef Sodium, it is characterised in that：Including Latamoxef Sodium, as claimed in claim 1
Compound (I) and pharmaceutically acceptable carrier, are prepared into the formulation of needs.
3. the pharmaceutical composition of Latamoxef Sodium according to claim 2, it is characterised in that：Pharmaceutically acceptable is carried
Body includes that diluent, excipient, filler, adhesive, wetting agent, disintegrant, sorbefacient, surfactant, absorption are carried
Body or lubricant.
4. the pharmaceutical composition of Latamoxef Sodium according to claim 2, it is characterised in that：The formulation include tablet,
Capsule, oral liquid, mouth containing agent, granule, electuary, pill, powder, paste, sublimed preparation, supensoid agent, pulvis, solution, injection
Agent, suppository, spray, drops or patch.
5. the preparation method of compound (I) described in claim 1, it is characterised in that comprising following operating procedure：A () will be partly
Summer crushes, and is extracted with 65～75% alcohol heat reflux, merges extract, is concentrated into without alcohol taste, uses petroleum ether, ethyl acetate successively
With water saturated extracting n-butyl alcohol, petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol extract is respectively obtained；(b) step
Suddenly in (a), n-butanol takes thing macroreticular resin removal of impurities, first with 20% ethanol elution, 9 column volumes, then with 65% ethanol elution 10
Individual column volume, collects 65% eluent, and reduced pressure concentration obtains 65% ethanol elution concentrate；65% ethanol elution in (c) step (b)
Concentrate is separated with purification on normal-phase silica gel, and it is 65 to use volume ratio successively:1、35:1、15:1 and 7:1 methylene chloride-methanol gradient elution
Obtain 4 components；D in () step (c), component 4 is further separated with purification on normal-phase silica gel, it is 12 to use volume ratio successively:1、7:1 and 1:1
Methylene chloride-methanol gradient elution obtain 3 components；What e in () step (d), the octadecylsilane of component 2 was bonded is anti-phase
Silica gel is separated, and with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 58%, is collected 11～15 column volume eluents, is washed
De- liquid is concentrated under reduced pressure to give compound (I).
6. the preparation method of compound (I) according to claim 5, it is characterised in that：Step (a) is returned with 70% ethanol heat
Stream is extracted, and merges extract.
7. the preparation method of compound (I) according to claim 5, it is characterised in that：The macroreticular resin is D101 types
Macroporous absorbent resin.
8. the preparation method of compound (I) according to claim 5, it is characterised in that：Dichloromethane generation is used in step (a)
Extracted for ethyl acetate, obtained dichloromethane extract.
9. application of the compound (I) described in claim 1 in the medicine for preparing treatment mRNA IN ADRIAMYCIN NEPHROPATHY syndrome.
10. the arbitrary described pharmaceutical composition of claim 2～4 prepare treatment mRNA IN ADRIAMYCIN NEPHROPATHY syndrome medicine in should
With.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019184570A1 (en) * | 2018-03-30 | 2019-10-03 | 杭州森泽医药科技有限公司 | Latamoxef sodium pharmaceutical composition and use thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019184570A1 (en) * | 2018-03-30 | 2019-10-03 | 杭州森泽医药科技有限公司 | Latamoxef sodium pharmaceutical composition and use thereof |
| JP2021517155A (en) * | 2018-03-30 | 2021-07-15 | ハンチョウ センゼ ファーマシューティカル テクノロジー カンパニー リミテッド | Latamoxef disodium pharmaceutical compositions and applications |
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