CN106309451A - Pharmaceutical composition of cefuroxime axetil and medical application of pharmaceutical composition - Google Patents
Pharmaceutical composition of cefuroxime axetil and medical application of pharmaceutical composition Download PDFInfo
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- CN106309451A CN106309451A CN201610670246.9A CN201610670246A CN106309451A CN 106309451 A CN106309451 A CN 106309451A CN 201610670246 A CN201610670246 A CN 201610670246A CN 106309451 A CN106309451 A CN 106309451A
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- cefuroxime axetil
- pharmaceutical composition
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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
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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
- A61K31/542—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 heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
- A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
- C07J63/008—Expansion of ring D by one atom, e.g. D homo steroids
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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)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/238—Saposhnikovia
Abstract
The invention discloses a pharmaceutical composition of cefuroxime axetil and medical application of the pharmaceutical composition. The pharmaceutical composition of the cefuroxime axetil contains the cefuroxime axetil and a natural product compound (I) with a novel structure, and when the cefuroxime axetil and the natural product acts independently, a therapeutical effect on alopecia is achieved; when the cefuroxime axetil and the natural product are combined to act, the therapeutical effect on the alopecia is further improved, and the pharmaceutical composition can be developed into a drug for treating the alopecia. Compared with the prior art, the pharmaceutical composition of the cefuroxime axetil and the medical application of the pharmaceutical composition have the prominent substantive features and significant progress.
Description
Technical field
The invention belongs to biomedicine field, relate to the new application of CEFUROXIME AXETIL, be specifically related to the medicine of CEFUROXIME AXETIL
Compositions and the application in alopecia thereof.
Background technology
CEFUROXIME AXETIL is the acetyl triethyl of cefuroxime.Disengage cefuroxime after hydrolysis in vivo and play its antibacterial work
Property, the mechanism of action of CEFUROXIME AXETIL, antimicrobial spectrum and antibacterial action are all same with cefuroxime.With other oral cephalosporin phases
Ratio, CEFUROXIME AXETIL includes Diplococcus pneumoniae, A group (hemolytic) streptococcus and S. aureus L-forms effect not to gram positive coccus
Weak, the effect to gram-negative bacteria such as gonococcus, hemophilus influenza, mucositis mora bacterium and escherichia coli section etc. is then better than cephalo gram
Lip river (cefaclor).CEFUROXIME AXETIL is second generation cephalosporin class antibiotic.Oral after gastrointestinal absorption, in esterase effect
It is hydrolyzed to cefuroxime rapidly and plays antibacterial action down.Activity and first generation cephalosporin to gram positive coccus similar or
The poorest, the quite stable but the beta lactamase producing staphylococcus and gram negative bacilli seems.Except methicillin-resistant Fructus Vitis viniferae ball
Outside bacterium, Enterococcus and listeria, other positive cocci (including anaerobic cocci) sensitivity equal to CEFUROXIME AXETIL.Cephalo furan
Monooctyl ester is poor to the antibacterial activity relatively cefazolin sodium of staphylococcus aureus, and the CEFUROXIME AXETIL of 1～2mg/L can suppress green grass or young crops respectively
The sensitive whole staphylococcus aureuses with drug resistance of mycin.
Up to now, there is not yet the dependency report of CEFUROXIME AXETIL and pharmaceutical composition thereof and alopecia.
Summary of the invention
It is an object of the invention to provide the pharmaceutical composition of a kind of CEFUROXIME AXETIL, containing cephalo in this pharmaceutical composition
Cefuroxime ester and the natural product of a kind of novel structure, CEFUROXIME AXETIL and this natural product can be with Synergistic treatment alopecias.
The above-mentioned purpose of the present invention is achieved by techniques below scheme:
The pharmaceutical composition of a kind of CEFUROXIME AXETIL, including CEFUROXIME AXETIL, compound (I) and pharmaceutically acceptable
Carrier, is prepared as the dosage form needed；Described compound (I) has a following structural formula:
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 includes tablet, capsule
Agent, oral liquid, suck agent, granule, electuary, pill, powder, unguentum, sublimed preparation, suspensoid, powder, solution, injection, bolt
Agent, spray, drop or patch.
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.
Further, compound (I) is the native compound separated from Radix Saposhnikoviae, and it comprises following separating step:
(a) by Radix Saposhnikoviae pulverize, with 75～85% alcohol heat reflux extract, united extraction liquid, be concentrated into without alcohol taste, successively use petroleum ether,
Ethyl acetate and water saturated n-butanol extraction, respectively obtain petroleum ether extract, acetic acid ethyl ester extract and n-butanol extraction
Thing；B in () step (a), n-butyl alcohol takes thing macroporous resin remove impurity, first with 8 column volumes of 25% ethanol elution, then use 70% second
12 column volumes of alcohol eluting, collect 70% eluent, and concentrating under reduced pressure obtains 70% ethanol elution concentrate；In (c) step (b) 70%
Ethanol elution concentrate purification on normal-phase silica gel separates, successively by dichloromethane-first that volume ratio is 85:1,45:1,25:1 and 15:1
Alcohol gradient elution obtains 4 components；D in () step (c), component 4 separates further by purification on normal-phase silica gel, be 20 by volume ratio successively:
1, the methylene chloride-methanol gradient elution of 15:1 and 1:1 obtains 3 components；E in () step (d), component 2 uses octadecylsilane
The reverse phase silica gel of bonding separates, and with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 72%, collects 10～16 cylinders
Long-pending eluent, eluent is concentrated under reduced pressure to give compound (I).
Further, in the preparation method of compound (I), described macroporous resin is D101 type macroporous adsorbent resin.
The application in the medicine preparing hair growth of the pharmaceutical composition of above-mentioned CEFUROXIME AXETIL.
Advantages of the present invention:
Containing CEFUROXIME AXETIL and the sky of a kind of novel structure in the pharmaceutical composition of the CEFUROXIME AXETIL that the present invention provides
So when product, CEFUROXIME AXETIL and this natural product independent role, alopecia had therapeutical effect；During the two synergy, right
The therapeutic effect of alopecia improves further, can develop into the medicine of hair growth.The present invention compared with prior art has prominent
The substantive distinguishing features gone out and significantly progress.
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
Separation method: Radix Saposhnikoviae (2kg) is pulverized by (a), extracts (15L × 3 time) with 80% 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 8 column volumes of 25% ethanol elution, then uses 70% ethanol elution
12 column volumes, collect 70% eluent, and concentrating under reduced pressure obtains 70% ethanol elution concentrate；C in () step (b), 70% ethanol is washed
De-concentrate purification on normal-phase silica gel separates, successively with volume ratio be 85:1 (10 column volumes), 45:1 (8 column volumes), 25:1 (10
Individual column volume) and the methylene chloride-methanol gradient elution of 15:1 (8 column volumes) obtain 4 components；Component in (d) step (c)
4 separate further by purification on normal-phase silica gel, successively with volume ratio be 20:1 (10 column volumes), 15:1 (8 column volumes) and 1:1 (6
Column volume) methylene chloride-methanol gradient elution obtain 3 components；E in () step (d), component 2 is bonded by octadecylsilane
Reverse phase silica gel separate, with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 72%, collect 10～16 column volumes and wash
De-liquid, 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 469.3238, can obtain molecular formula in conjunction with nuclear-magnetism feature is
C30H44O4, degree of unsaturation is 9.Hydrogen nuclear magnetic resonance modal data δH(ppm, CDCl3, 600MHz): H-1 (1.49, m), H-1 (2.87,
Ddd, J=13.3,7.0,4.2Hz), H-2 (2.41, ddd, J=15.4,6.8,4.2Hz), H-2 (2.65, ddd, J=15.4,
11.2,7.0Hz), and H-5 (1.37, d, J=11.2Hz), H-6 (1.68, m), H-6 (1.93, m), H-7 (1.73, m), H-7
(1.87, m), H-9 (1.60, d, J=9.4Hz), H-11 (4.17, d, J=9.1Hz), H-15 (5.43, d, J=10.3Hz), H-
16 (5.52, d, J=10.3Hz), and H-18 (2.46, d, J=8.4Hz), H-19 (1.41, m), H-20 (1.10, m), H-21
(1.28, m), H-21 (1.48, m), H-22 (1.36, m), H-22 (1.51, m), H-23 (1.32, s), H-24 (9.82, s), H-
25 (1.06, s), H-26 (1.17, s), H-27 (1.24, s), H-28 (0.87, s), H-29 (0.90, d, J=6.3Hz), H-30
(0.93, d, J=6.1Hz), and OH-11 (3.13, s), OH-12 (4.73, brs)；Carbon-13 nmr spectra data δC(ppm, CDCl3,
125MHz): 39.2 (CH2, 1-C), 22.3 (CH2, 2-C), 207.6 (C, 3-C), 34.5 (C, 4-C), 63.2 (CH, 5-C), 20.4
(CH2, 6-C), 40.9 (CH2, 7-C), 57.8 (C, 8-C), 51.6 (CH, 9-C), 38.2 (C, 10-C), 71.9 (CH, 11-C),
146.7 (C, 12-C), 119.2 (C, 13-C), 36.3 (C, 14-C), 128.9 (CH, 15-C), 139.5 (CH, 16-C), 41.4
(C, 17-C), 47.3 (CH, 18-C), 40.1 (CH, 19-C), 40.7 (CH, 20-C), 30.7 (CH2, 21-C), 39.2 (CH2, 22-
C), 22.3 (CH3, 23-C), 201.1 (CH, 24-C), 15.7 (CH3, 25-C), 19.4 (CH3, 26-C), 20.9 (CH3, 27-C),
19.1(CH3, 28-C), 17.2 (CH3, 29-C), 21.3 (CH3, 30-C).Infrared spectrum shows that this compound contains hydroxyl
(3478cm-1), carbonyl (1760cm-1), double bond (1663cm-1) and aldehyde radical (1641cm-1)。13In C-NMR, DEPT and hsqc spectrum
Show 30 carbon signals, including seven methyl, six methylene, nine methines (even oxygen carbon and two alkene carbon, one
Individual aldehyde radical), and eight quaternary carbons (ketone group, an oxygen-containing olefinic quaternary carbon, an olefinic quaternary carbon), function above structure is tied again
Close insatiable hunger sum and show that this compound is pentacyclic triterpene structure.1H-NMR spectrum combines five tertiary methyl proton letters that hsqc spectrum shows
Number δH1.32 (3H, s), 1.06 (3H, s), 1.17 (3H, s), 1.24 (3H, s) He 0.87 (3H, s), two secondary methyl proton letters
Number δH0.90 (3H, d, J=6.3Hz), 0.93 (3H, d, J=6.1Hz) and1H-NMR data show that this compound is ursane
Type triterpenoid compound.H-5 and H in HMBC spectrum3The dependency of-23 and C-24 shows that C-4 position is connected with an aldehyde radical, and NOESY composes
Middle H-24 and H3The coherent signal hint aldehyde radical of-25 is in β position.Understand containing hydroxyl in structure from ultrared spectrum, and from1H-NMR
Data understand containing two hydroxyls.H-9 and H-18 and C-12, H-18 and H in HMBC spectrum3-27 and C-13, OH-12 and C-12 phase
OFF signal and their carbon chemical shifts show that this compound exists enol-type structure, hydroxyl be connected to C-12 position and C-12 and
The double bond that C-13 is formed constitutes enol-type structure, the coherent signal of OH-11 Yu C-11 and chemical potential in composing further according to HMBC
Move and confirm that another-OH is connected in C-11 position.Another C-15 Yu C-16 also forms double bond structure, and C-3 position forms ketone group.In HMBC spectrum
H3The dependency of-23 and H-24 Yu C-3 and their carbon chemical shifts are confirmed C-3 position further and are formed ketone group.Comprehensive hydrogen spectrum,
Carbon spectrum, HMBC spectrum and NOESY spectrum, and document is about correlation type nuclear magnetic data, can substantially determine that this compound is as follows,
Spatial configuration is determined by ECD test further, and theoretical value is basically identical with experiment value.
This compound chemical formula and carbon atoms numbered are as follows:
Embodiment 2: pharmacological action
Alopecia is a kind of most common dermatosis.For a long time, people are devoted to find and research and develop hair growth always
Medicine, such as glucocorticoid, minoxidil etc..But up to the present, still do not have a kind of medicine can cure alopecia completely, and deposit
In bigger untoward reaction.Therefore, the medicine of the preventing and treating alopecia develop determined curative effect, having no adverse reaction has important society's meaning
Justice and economic implications.The present embodiment uses cyclophosphamide (Cyclophosphamide, CTX) to set up mice depilation model, observes
The medicine effect to improving depilation mouse hair growth.
1, materials and methods
1.1 animal
SPF level, male C57BL/6 mice, weight 18～20g, Shanghai Slac Experimental Animal Co., Ltd..Raise ring
Border: room temperature controls at 24～26 DEG C, light every 12h light and shade alternately, ad lib, the next day change bedding and padding.
1.2 reagent and sample
CEFUROXIME AXETIL is purchased from Nat'l Pharmaceutical & Biological Products Control Institute.Compound (I) is made by oneself, and preparation method is shown in embodiment 1.
Cyclophosphamide (Hengrui Medicine Co., Ltd., Jiangsu Prov.).CBA detection kit (U.S., BD company), CD4 detection kit
(Shanghai Ying Xin laboratory equlpment company limited), CD8 detection kit (Shanghai Ying Xin laboratory equlpment company limited).
1.3 instrument
JEM-1010 type Electronic Speculum (Japan, NEC company), C6 type flow cytometer (U.S., BD company), MK3 type enzyme
Mark instrument (U.S., Thermo company).
Prepared by 1.4 mice group and model
C57BL/6 mice anesthetic machine is anaesthetized.After anesthesia, Colophonium and paraffin are melted in the ratio Hybrid Heating of 1: 1, and
Uniform application in item back, solidify hardening after throw off, induced growth phase hair, every mice depilation area be about 2.0cm ×
2.0cm.It is careful not to burned mouse skin.Lose hair or feathers latter 9 days (generation of mouse back skin induced growth phase hair follicle), according at random
Numeral table, is divided into 5 groups by mice, and often group 20, is blank group, model control group, CEFUROXIME AXETIL group respectively
(280mg·kg-1), compound (I) group (280mg kg-1), CEFUROXIME AXETIL and compound (I) compositions group [140mg kg-1CEFUROXIME AXETIL+140mg kg-1Compound (I)].After all mices depilation district subcutaneous injection CTX150mg/kg, model group
Giving free rein to growth, blank group gives the treatment of normal saline (100mg/kg) gavage, other group medicine gavage treatments, continues
8 weeks.
1.5 tissue sampling
1,2,4,8 weeks the most upon administration, often group randomly selected each 5 of mice, and row eye socket is taken a blood sample, every 1～2mL.With
Detecting in ELISA: often group takes 2 blood samples, add EDTA anticoagulant, 3000r/min is centrifuged 30min and takes supernatant, in-20 DEG C of preservations
Standby.For Flow cytometry: often group takes 3 blood samples, separate serum, save backup in-70 DEG C.After all animals take blood
Put to death immediately, take its epilating area skin histology.Fixing through 10% formalin, routine paraffin wax embeds, paraffin section, slice thick
4～5 μm, save backup at-80 DEG C.
1.6 ELISA detect peripheral blood CD4+、CD8+Expression
20min is balanced under sample room temperature.Standard sample wells, sample aperture and blank well are set.What is all not added with blank well, standard
Sample wells respectively adds the standard substance 50 μ L of variable concentrations.Sample to be tested first adds Sample dilution 40 μ L, then adds sample to be tested 10 μ L, subsequently
Standard sample wells and sample aperture (blank well is not added with) add the detection antibody 100 μ L of horseradish peroxidase-labeled, seal with shrouding film
Living reacting hole, 37 DEG C of calorstats hatch 60min.Discarding liquid, absorbent paper pats dry, every hole adds cleaning mixture, stands 1min, gets rid of
Cleaning mixture, absorbent paper pats dry, and is repeated 5 times.The each 50 μ L of porose addition substrate A, B, 37 DEG C of lucifuges hatch 15min.Add termination
Liquid 50 μ L, in 15min, measures each hole OD value at 450nm wavelength.Statistics CD4 and CD8 OD value, using CD4/CD8 average as
Result carries out statistical analysis.
1.7 statistical method
Result represents with mean ± standard deviation (x ± s).Using SPSS17.0 statistical software analytical data, comparing between group should
Use one factor analysis of variance.
2, experimental result
2.1 changes of body mass and hair growth situation
Mice is terminated to experiment through CTX induction depilation, each group Mice Body quality no significant difference (P ＞ 0.05).Lose hair or feathers little
Mus after CEFUROXIME AXETIL, compound (I), CEFUROXIME AXETIL and compound (I) compositions are administered 1～2 week, each group mice loses hair or feathers
District's local skin is gradually transformed into grey black by pink colour, and mice depilation skin grey black region, district is substantially than model group and physiology salt
Water group wants big；Being administered to 4～8 weeks, each group mice depilation district is black, and has hair gradually to grow, extends.Administration group hair phase
For model group and normal saline group, hair is the finest and close.
2.2 couples of depilation mouse peripheral blood CD4+/CD8+The impact of ratio expression
CEFUROXIME AXETIL group, compound (I) group, CEFUROXIME AXETIL group and compound (I) compositions group peripheral blood CD4+/
CD8+Ratio prolongation over time, on a declining curve.1,2,3,4 weeks, with model control group ratio, CEFUROXIME AXETIL group and chemical combination
Thing (I) compositions group peripheral blood CD4+/CD8+Ratio is remarkably decreased (P ＜ 0.01)；With model control group ratio, CEFUROXIME AXETIL group,
Compound (I) group peripheral blood CD4+/CD8+Ratio declines (P ＜ 0.05).Result of the test is shown in Table 1.
Table 1 is to depilation mouse peripheral blood CD4+/CD8+The impact of ratio expression
| Group | 1 week | 2 weeks | 3 weeks | 4 weeks |
| Model control group | 5.48±0.06 | 5.37±0.05 | 4.99±0.09 | 4.83±0.11 |
| CEFUROXIME AXETIL group | 5.15±0.05 | 4.76±0.06 | 4.40±0.17 | 4.12±0.08 |
| Compound (I) group | 4.87±0.02 | 4.34±0.13 | 4.16±0.06 | 3.65±0.27 |
| CEFUROXIME AXETIL and compound (I) compositions group | 3.94±0.04 | 3.67±0.02 | 3.29±0.25 | 2.94±0.08 |
The depilation the most frequently used laboratory animal of model is C57BL/6 mice, and owing to it is coloured kind, skin color is with hair follicle
Grow and show different colors, be research hair follicle development and a kind of well laboratory animal of regeneration.
At present the pathophysiological mechanism about alopecia is not yet clear and definite, possible reason is main and local infection, neurotoxic substance,
The factor such as spirit depressing, endocrine factors is correlated with.Recently as heredity, gene, the development of molecular level, the most all
Many scholars think that alopecia is mainly a kind of autoimmune inflammation disease immune-mediated by T cell, expose owing to hair follicle is abnormal
In potential immunocompetent immune system, then activating powerful immune system by the antigenic substance of hair follicle, induction release is a large amount of
Inflammation, causes alopecia then.CD4+And CD8+T cell in hair loss patient hair follicle and around infiltration cause alopecia
Key, CD8+T cell is considered the hair follicle direct cytotoxicity of performance always, and CD4+T cell plays auxiliary cytosis,
In the pathogenic process of alopecia, both play a role jointly.
CEFUROXIME AXETIL, compound (I), CEFUROXIME AXETIL group and compound (I) compositions maintaining treatment are to depilation mice
There is obvious curative effects, significantly improve the hair growth situation in mice depilation district, by lowering peripheral blood CD4+/CD8+Ratio comes
Playing a role, the Drug therapy for clinical alopecia provides new therapeutic scheme.Wherein, CEFUROXIME AXETIL and compound (I) connection
The cooperation used time, notable to the improvement result effect of hair growth, it is better than CEFUROXIME AXETIL or compound (I) individually acts on effect
Really, the medicine of preventing and treating alopecia 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 (6)
1. the pharmaceutical composition of a CEFUROXIME AXETIL, it is characterised in that: include CEFUROXIME AXETIL, compound (I) and pharmaceutically
Acceptable carrier, is prepared as the dosage form needed；Described compound (I) has a following structural formula:
The pharmaceutical composition of CEFUROXIME AXETIL the most according to claim 1, it is characterised in that: pharmaceutically acceptable carries
Body includes that diluent, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carry
Body or lubricant.
The pharmaceutical composition of CEFUROXIME AXETIL the most according to claim 1, it is characterised in that: described dosage form include tablet,
Capsule, oral liquid, suck agent, granule, electuary, pill, powder, unguentum, sublimed preparation, suspensoid, powder, solution, injection
Agent, suppository, spray, drop or patch.
The pharmaceutical composition of CEFUROXIME AXETIL the most according to claim 1, it is characterised in that: compound (I) is from Radix Saposhnikoviae
In the native compound separated, it comprises following separating step: Radix Saposhnikoviae is pulverized by (a), with 75～85% alcohol heat reflux
Extract, united extraction liquid, be concentrated into without alcohol taste, successively with petroleum ether, ethyl acetate and water saturated n-butanol extraction, respectively
To 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 8 column volumes of 25% ethanol elution, then with 12 column volumes of 70% ethanol elution, collects 70% eluent, decompression
It is concentrated to give 70% ethanol elution concentrate；C in () step (b), 70% ethanol elution concentrate purification on normal-phase silica gel separates, use successively
Volume ratio is that the methylene chloride-methanol gradient elution of 85:1,45:1,25:1 and 15:1 obtains 4 components；Group in (d) step (c)
Divide 4 to separate further by purification on normal-phase silica gel, obtain with the methylene chloride-methanol gradient elution that volume ratio is 20:1,15:1 and 1:1 successively
To 3 components；E reverse phase silica gel that in () step (d), component 2 is bonded by octadecylsilane separates, and by concentration expressed in percentage by volume is
The methanol aqueous solution isocratic elution of 72%, collects 10～16 column volume eluents, and eluent is concentrated under reduced pressure to give compound
(Ⅰ)。
The preparation method of compound the most according to claim 4 (I), it is characterised in that: described macroporous resin is D101 type
Macroporous adsorbent resin.
6. pharmaceutical composition the answering in the medicine preparing hair growth of the arbitrary described CEFUROXIME AXETIL of Claims 1 to 4
With.
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| CN106117166A (en) * | 2016-06-23 | 2016-11-16 | 崔坤峰 | The pharmaceutical composition of amrinone and the application in hypertension therapeutic thereof |
Citations (1)
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| CN105324389A (en) * | 2013-04-24 | 2016-02-10 | 艾伯维公司 | 2,2-difluoropropionamide derivatives of bardoxolone methyl, polymorphic forms and methods of use thereof |
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2016
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105324389A (en) * | 2013-04-24 | 2016-02-10 | 艾伯维公司 | 2,2-difluoropropionamide derivatives of bardoxolone methyl, polymorphic forms and methods of use thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106117166A (en) * | 2016-06-23 | 2016-11-16 | 崔坤峰 | The pharmaceutical composition of amrinone and the application in hypertension therapeutic thereof |
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