CN106074583A - A kind of phenylpropanoids and pharmaceutically acceptable salt application in the medicine of preparation treatment diseases associated with inflammation thereof - Google Patents
A kind of phenylpropanoids and pharmaceutically acceptable salt application in the medicine of preparation treatment diseases associated with inflammation thereof Download PDFInfo
- Publication number
- CN106074583A CN106074583A CN201610153535.1A CN201610153535A CN106074583A CN 106074583 A CN106074583 A CN 106074583A CN 201610153535 A CN201610153535 A CN 201610153535A CN 106074583 A CN106074583 A CN 106074583A
- Authority
- CN
- China
- Prior art keywords
- acid
- phenylpropanoids
- medicine
- inflammation
- apply
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- C07H1/06—Separation; Purification
- C07H1/08—Separation; Purification from natural products
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/203—Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems
Abstract
The present invention relates to pharmaceutical technology field, disclose the application in the medicine of preparation treatment diseases associated with inflammation of a kind of phenylpropanoids and pharmaceutically acceptable salt thereof.This phenylpropanoids demonstrates the content that can suppress cellular inflammation factor NO, suppression cellular inflammation factor TNF α, IL 1 β, the expressional function of IL 6, there is the inhibitory action of (OH) to hydroxyl radical free radical, and then there is antiinflammatory and antioxidant activity, for diseases associated with inflammation, the exploitation such as the medicine of the diseases such as cervicitis, endometritis, pelvic inflammatory disease, mastitis, pharyngolaryngitis and/or arthritis provides direction.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to a kind of phenylpropanoids and pharmaceutically acceptable salt thereof in system
Application in the medicine of standby treatment diseases associated with inflammation.
Background technology
The constituent structure extracting isolated from natural drug is various, active significantly, and it is carried out isolated and purified, structure
Modify, transform and complete synthesis, an always main thought of new drug development.
TNF-α: be a kind of can direct killing tumor cell and to normal cell without the cytokine of overt toxicity, be so far
One of bioactie agent that the direct killing function of tumor that found till the present is the strongest, but its toxic and side effects is the tightest
Weight.
IL-1 β: collaborative APC and the T cell activation of stimulating, promotion B cell proliferation and secretory antibody when local low concentration, enter
Row immunomodulating.There is endocrine effect during a large amount of generation: induced liver acute phase protein synthesizes, cause heating and cachexia.
IL-6: mankind's IL-6 gene is positioned on No. 7 chromosome；IL-6 molecular weight is between 21～30KD.Main by list
Core macrophage, Th2 cell, vascular endothelial cell, fibroblast produce.Activating B cell can be stimulated to breed, and secretion is anti-
Body；Stimulate T cell propagation and CTL activation；Cell cultured supernatant synthesized acute phase albumen, participates in inflammatory reaction；Promote that hemocyte is sent out
Educate.
IL-6 can be synthesized by various kinds of cell, including activation T cell and B cell, monocytes/macrophages, endotheliocyte,
Epithelial cell and fibroblast etc..The target cell of IL-6 effect is a lot, thin including macrophage, hepatocyte, static T
Born of the same parents, the B cell of activation and plasma cell etc.；Its biological effect is the most sufficiently complex.
OH is the reactive oxygen species of most activity in biosystem, can cause DNA in cell and organism, protein and fat
Matter oxidative damage.
Macrophage can produce inflammation medium and participate in inflammatory reaction, and wherein, NO is the important cellular inflammation factor, NO
Participating in multiple pathological processes, excessive NO can promote generation and the development of diseases associated with inflammation, and can also induce other inflammation
The factor.
Therefore, seek new compound, to suppress the content of cellular inflammation factor NO, suppress cellular inflammation factor TNF-
The expressional function of α, IL-1 β, IL-6, the activity of suppression hydroxyl radical free radical (-OH), it is applied to the treatment of diseases associated with inflammation, right and wrong
Often it is necessary.
Radix Flemingiae Philippinensis medical material is that pulse family (Leguminosae) Moghania (Flemingl.Roxb. or Moghania) plant is big
The dry root of leaf Radix Flemingiae Philippinensis (Moghaniamacrophylla (Willd.) O.Kuntze), is distributed mainly on the southeast in China
Area.This plant is in Chinese Plants will (1995,41:313), TaiWan, China flora (1977,3:258), Hainan flora
(1955, pp707) and extensively are said in (1965,2:311), " Chinese Higher plant illustrated handbook " (1972,2:510), China's main plant figure
State flora is all included in (1956, pp361).Radix Flemingiae Philippinensis medical material is the genuine medicinal materials of Guangxi province, and history is loaded in " plant name reality
Figure is examined ", there is medication the most among the people basis.Its nature and flavor are sweet, micro-puckery, flat, have the effects such as removing damp-heat, are mainly used in treatment
The gynaecopathias such as rheumatic ostalgia, traumatic injury, chronic nephritis, dysmenorrhea and leucorrhea are many.This medical material has recorded the most into version in 2005
" Chinese Pharmacopoeia " annex.
The composition that Flemingia macrophylla has been reported mainly has flavonoid, steroid, terpenoid, Anthraquinones, volatile oil composition, all has
Having certain pharmacologically active, its pharmacologically active is various, reports the more neuroprotective that has, and antiinflammatory, antioxidation, to disease
The anthelmintic action of pathogenic microorganism, parahormone effect, cytotoxicity, antibacterial action and immunological enhancement, antifatigue effect.
Radix Flemingiae Philippinensis is now widely used for the Chinese patent medicine of the type such as gynecological, rheumatic arthralgia and produces, such as FUKE QIANJIN PIAN, gynecological
A thousand pieces of gold capsule, JINJI CHONGJI, JINJI JIAONANG etc., this type of Chinese patent medicine is mainly used in gynaecopathia, and (dysmenorrhea, cold uterus be infertile, uterus
Sagging, pelvic inflammatory disease, mastitis, leucorrhea are many, blood deficiency in puerperal, arthralgia, waist and knee in puerperal, hypogalactia and breast ulcer etc.), weak anemia
(woman anemia, deficient qi and blood and the after being ill deficiency of vital energy etc.).In recent years, what clinical report was more is that FUKE QIANJIN PIAN is scorching in treatment gynecological
Effect in terms of disease.
At present, in the document of Radix Flemingiae Philippinensis, the document of report phenylpropanoids is few, finds effective Phenylpropanoid Glycosides class
Noval chemical compound, carries out isolated and purified, structural modification and synthesis, developing new drug to it, is applied to the treatment of diseases associated with inflammation, meaning
Great.
Summary of the invention
The technical problem to be solved in the present invention is, finds a kind of effective ingredient, and it can suppress containing of cellular inflammation factor NO
Amount, suppresses cellular inflammation factor TNF-α, the expressional function of IL-1 β, IL-6, and the suppression with (-OH) to hydroxyl radical free radical is made
With, can apply in the medicine of preparation treatment diseases associated with inflammation.The present invention provides a kind of phenylpropanoids, and it can suppress
The content of cellular inflammation factor NO, suppresses cellular inflammation factor TNF-α, the expressional function of IL-1 β, IL-6, has to hydroxyl certainly
By the inhibitory action of (-OH) of base, and then having antiinflammatory and antioxidant activity, the exploitation for anti-inflammatory drug provides direction, is used for
Treatment related inflammation disease, such as cervicitis, endometritis, pelvic inflammatory disease, mastitis, pharyngolaryngitis and/or arthritis etc..
It is an object of the invention to provide the medical applications of a kind of phenylpropanoids.
There is provided a kind of phenylpropanoids and pharmaceutically acceptable salt thereof as the medicine of preparation treatment diseases associated with inflammation
Application in thing, the structural formula of described phenylpropanoids is as shown in formula I:
The structure of described phenylpropanoids pharmaceutically acceptable salt is as shown in formula II or formula III:
Wherein, R is mineral acid, R1Or R2Or R3For any one in sulfonate radical, alkali metal ion or ammonium root or any two
Plant or any three kinds.
Preferably, described phenylpropanoids and pharmaceutically acceptable salt thereof are in the preparation suppression cellular inflammation factor
The content of NO or suppression cellular inflammation factor TNF-α, IL-1 β, IL-6 express or the active medicine of suppression hydroxyl radical free radical
In application, be applied to treat diseases associated with inflammation medicine in.
Preferably, described diseases associated with inflammation is cervicitis, endometritis, pelvic inflammatory disease, mastitis, pharyngolaryngitis and/or pass
Joint inflammation.
Described pharmaceutically acceptable salt is that phenylpropanoids shown in formula I pharmaceutically can connect with what acid or alkali were formed
The salt being subject to, wherein, in formula II, R is mineral acid, in formula III, R1Or R2Or R3In sulfonate radical, alkali metal ion or ammonium root
Any one or any two kinds or any three kinds.
Described mineral acid is hydrochloric acid, hydrobromic acid, Fluohydric acid., hydroiodic acid, sulphuric acid, nitric acid, carboxylic acid, phosphoric acid or lactic acid；Described
Sulfonate radical is the sulfonate radical with aryl；Described alkali metal ion is potassium ion, sodium ion, calcium ion, magnesium ion or lithium ion.
The described sulfonate radical with aryl is benzenesulfonic acid root or p-methyl benzenesulfonic acid root.
Described phenylpropanoids pharmaceutically acceptable salt is ammonium salt.
Described medicine contains the adjuvant and/or carrier pharmaceutically allowed.
Preferably, described medicine is possibly together with other active ingredient.
Preferably, described medicine is possibly together with in Radix Rosae Laevigatae, Fructus Zanthoxyli Dissiti, Caulis Spatholobi, Caulis Mahoniae, Herba Andrographis, Radix Angelicae Sinensis, Radix Codonopsis
One or more.
Preferably, described medicine is possibly together with in Radix Rosae Laevigatae, Fructus Zanthoxyli Dissiti, Caulis Spatholobi, Caulis Mahoniae, Herba Andrographis, Radix Angelicae Sinensis, Radix Codonopsis
The extract of one or more.
Described extract for press patent announcement CN1078079C, CN1170549C, CN1158087C, CN1330335C,
Carrying described in any one of CN1296071C, CN1321631C, CN1296072C, CN1296073C or several patent documents
Access method prepares.
The dosage form of described medicine is tablet, capsule, powder, granule, pill, solution, suspensoid, syrup, note
Penetrate agent, ointment, suppository or spray.
It is an object of the invention to from traditional prescriptions of Chinese medicine, by the prescription from FUKE QIANJIN PIAN and FUKE QIANJIN JIAONANG
In, prepare a kind of new phenylpropanoids by solvent extraction, column chromatography for separation, preparation liquid phase separation, purification, and by real
Checking is real, and it can apply to diseases associated with inflammation, such as cervicitis, endometritis, pelvic inflammatory disease, mastitis, pharyngolaryngitis and/or pass
The treatment of the diseases such as joint is scorching.
Specifically, inventor by from FUKE QIANJIN PIAN, FUKE QIANJIN JIAONANG prescription, choose the dry of Flemingia macrophylla
Dry, by solvent extraction, column chromatography for separation, preparation liquid phase separation, purification, obtain phenylpropanoids of the present invention,
Then this phenylpropanoids is carried out test cell line, measure its to cellular inflammation factor NO, TNF-α, IL-1 β, IL-6 and
The suppression degree of hydroxyl radical free radical (-OH), experiment shows, this phenylpropanoids is at concentration (8.75 15.75 μ g/mL) model
Enclose the rising of the interior NO content that LPS is caused and have obvious inhibitory action, and show obvious dose-dependence.In concentration
The Raw 264.7 cellular inflammation factor TNF-α that in the range of (8.75 15.75 μ g/mL), LPS causes, IL-1 β, IL-6 content all has
Significantly inhibitory action (p ＜ 0.05), and show obvious dose-dependence, at concentration (5.25 15.75 μ g/mL) model
Enclose the interior OH changes of contents that LPS is caused and have obvious inhibitory action (p ＜ 0.05), and show dose-dependence.
Beneficial effects of the present invention:
The present invention is square degree at Chinese medicine, extract from Chinese medicine FUKE QIANJIN PIAN, FUKE QIANJIN JIAONANG,
Separate, purification obtains a kind of phenylpropanoids, the experiment proved that, this phenylpropanoids demonstrates and can suppress cell
The content of inflammatory factor NO, suppresses cellular inflammation factor TNF-α, the expressional function of IL-1 β, IL-6, has hydroxyl radical free radical
The inhibitory action of (-OH), for diseases associated with inflammation, as cervicitis, endometritis, pelvic inflammatory disease, mastitis, pharyngolaryngitis and/or
The exploitation of the medicine of the diseases such as arthritis provides direction.
New phenylpropanoids simple in construction, purity that the present invention provides are high, and extraction separation method is easy, be prone to
Synthesis, is suitable for the commercial application of new drug.
Accompanying drawing explanation
Fig. 1 is the hydrogen nuclear magnetic resonance spectrogram of phenylpropanoids of the present invention.
Fig. 2 is the carbon-13 nmr spectra figure of phenylpropanoids of the present invention.
Fig. 3 is that phenylpropanoids of the present invention affects figure to cytoactive.
Fig. 4 is the phenylpropanoids of the present invention inhibitory action figure to NO.
Fig. 5 is the phenylpropanoids of the present invention inhibitory action figure to TNF-α.
Fig. 6 is the phenylpropanoids of the present invention inhibitory action figure to IL-1 β.
Fig. 7 is the phenylpropanoids of the present invention inhibitory action figure to IL-6.
Fig. 8 is the phenylpropanoids of the present invention inhibitory action figure to OH.
Detailed description of the invention
Further illustrate the present invention below in conjunction with Figure of description and specific embodiment, but embodiment is not to the present invention
Limit in any form.Unless stated otherwise, the present invention uses reagent, method and apparatus are the examination of the art routine
Agent, method and apparatus.Unless stated otherwise, to be the art conventional commercial former for raw material used by the present embodiment and equipment
Material and equipment.
The compound of the present invention is the phenylpropanoids shown in described formula I and formula II or formula III this change shown
Compound pharmaceutically acceptable salt.This compound can use the method extracted with Flemingia macrophylla that the present invention provides for raw material
Prepare, it is also possible to the structural formula provided according to the present invention combines the methods such as the chemosynthesis of employing this area and prepares.
As the salt of phenylpropanoids of the present invention, as long as pharmaceutically acceptable salt, can be enumerated as
The inorganic acid salt formed with the mineral acid such as hydrochloric acid, hydrobromic acid, Fluohydric acid., hydroiodic acid, sulphuric acid, nitric acid, carboxylic acid, phosphoric acid, lactic acid；With
The sulfonate that sulfonic acid is formed；The alkali metal salt formed with the alkali-metal hydroxide such as potassium, sodium, calcium, magnesium, lithium, is formed with ammonium
Ammonium salt etc..
Phenylpropanoids of the present invention can be used as cervicitis, endometritis, pelvic inflammatory disease, mastitis, pharyngolaryngitis and/
Or the medicine of the diseases associated with inflammation such as arthritis.
The compounds of this invention can be used as pharmaceutical composition together with the adjuvant pharmaceutically allowed and/or carrier, it is also possible to
In the case of adding the adjuvant that pharmaceutically allows and/or carrier with Radix Rosae Laevigatae, Fructus Zanthoxyli Dissiti, Caulis Spatholobi, Caulis Mahoniae, Herba Andrographis,
One or more Chinese crude drugs or the combination of extract in Radix Angelicae Sinensis, Radix Codonopsis are used as pharmaceutical composition, and the compounds of this invention is all right
Pharmaceutical composition it is used as together with other pharmaceutically acceptable active ingredient.
As pharmaceutical composition, can be tablet, capsule, powder, granule, pill, solution, suspensoid, syrup
Agent, injection, ointment, suppository, spray etc..
Further, tablet can be the sugar-coat made in the case of adding the adjuvant and/or carrier pharmaceutically allowed
Sheet, Film coated tablets, enteric coatings ply or two-ply, multilayer tablet.
Adjuvant and/or the carrier of the present invention can be such that
Make solid preparation, it is possible to use additive, such as sucrose, lactose, cellulose sugar, maltose alcohol, glucose, shallow lake
Powder class, agar, alginates, chitin, chitosan class, pectin class, Radix Acaciae senegalis class, gelatin class, collagen class, cheese egg
In vain, albumin, calcium phosphate, Sorbitol, glycine, glycerol, Polyethylene Glycol, sodium bicarbonate, Talcum etc..
Make semi-solid preparation, it is possible to use of animal or plant nature oils and fats (olive oil, Semen Maydis oil, Oleum Ricini etc.), mineral oil
Fat (vaseline, white vaseline, solid paraffin etc.), wax class (Jojoba oil, Brazil wax, Cera Flava etc.), partial synthesis or complete
The fatty acid glyceride (lauric acid, myristic acid, Palmic acid etc.) etc. of synthesis.
Make liquid preparation, can use additive, such as sodium chloride, glucose, Sorbitol, glycerol, olive oil, the third two
Alcohol, ethanol etc..In the case of especially making injection, it is possible to use aseptic aqueous solution, such as normal saline, isotonic solution, oiliness
Liquid, such as Oleum Sesami, soybean oil.Furthermore it is also possible to as required, and with suitable suspending agent, such as sodium carboxymethyl cellulose, nonionic
Surfactant, cosolvent, such as benzyl benzoate, benzyl alcohol etc..
The amount of the effective ingredient of these preparations is 0.01～80 weight % of preparation, is suitably 1～50 weight %, dosage
Symptom according to patient, body weight, age etc. are different and change.
The preparation of embodiment 1 phenylpropanoids
The present embodiment provides a kind of preparation method of phenylpropanoids shown in formula I, comprises the steps:
S1. take Flemingia macrophylla 50kg, with root as raw material, be dried, be cut into small pieces.Alcohol reflux through 8 times amount 60%
Extract 3 times, each 2 hours, extracting solution is merged, is concentrated into without alcohol taste, obtains extractum standby；
S2. the extractum after concentrating in step S1 is dissolved in 10L water, uses D101 macroporous adsorptive resins to wash it
De-, eluant is water, 3 column volumes of eluting, collection eluent, and named MM-1 is standby；
S3. with anti-phase ODS column chromatography, the flow point MM-1 collected in step S2 being carried out eluting, eluant is methanol-water
System, its volume ratio is 25:75,18 column volumes of eluting, collects the eluent of a flow point by every 3 column volumes, in order
Collect 6 flow points, be respectively designated as: MM-11, MM-12, MM-13, MM-14, MM-15, MM-16 are standby；
S4. by the flow point MM-12 collected in step S3 with preparing liquid phase separation, preparative liquid chromatography post is: YMC,
20mm*250mm, flow velocity: 5ml/min, flowing is methanol-water-acetic acid system mutually, methanol: water: the volume ratio of acetic acid is 25:75:
0.01, collect eluent by peak sequence, collect 7 flow points altogether, be respectively designated as MM-121, MM-122, MM-123, MM-
124, MM-125, MM-126, MM-127, standby；
S5. being purified with preparing liquid phase by the flow point MM-126 collected in step S4, preparative liquid chromatography post is: YMC,
20mm*250mm, flow velocity: 5ml/min, flowing is methanol-water-acetic acid system mutually, methanol: water: the volume ratio of acetic acid is 15:85:
0.01, collect eluent, after recrystallization, obtain described phenylpropanoids.
The preparation of embodiment 2 phenylpropanoids
The present embodiment provides a kind of preparation method of phenylpropanoids shown in formula I, comprises the steps:
S1. take Flemingia macrophylla 40kg, with root as raw material, be dried, be cut into small pieces.Alcohol reflux through 6 times amount 50%
Extract 2 times, each 1 hour, extracting solution is merged, is concentrated into without alcohol taste, obtains extractum standby；
S2. the extractum after concentrating in step S1 is dissolved in 5L water, uses D101 macroporous adsorptive resins to wash it
De-, eluant is ethanol and the volume ratio of water is 15:85,3 column volumes of eluting, collects eluent, and named MM-1 is standby；
S3. with anti-phase ODS column chromatography, the flow point MM-1 collected in step S2 being carried out eluting, eluant is methanol-water
System, its volume ratio is 20:80,18 column volumes of eluting, collects the eluent of a flow point by every 3 column volumes, in order
Collect 6 flow points, be respectively designated as: MM-11, MM-12, MM-13, MM-14, MM-15, MM-16 are standby；
S4. by the flow point MM-12 collected in step S3 with preparing liquid phase separation, preparative liquid chromatography post is: YMC,
20mm*250mm, flow velocity: 10ml/min, flowing is methanol-water-acetic acid system mutually, methanol: water: the volume ratio of acetic acid is 35:
65:0.01, collects eluent by peak sequence, collects 7 flow points altogether, be respectively designated as MM-121, MM-122, MM-123, MM-
124, MM-125, MM-126, MM-127, standby；
S5. being purified with preparing liquid phase by the flow point MM-126 collected in step S4, preparative liquid chromatography post is: YMC,
20mm*250mm, flow velocity: 5ml/min, flowing is methanol-water-acetic acid system mutually, methanol: water: the volume ratio of acetic acid is 15:85:
0.01, collect eluent, after recrystallization, obtain described phenylpropanoids.
The preparation of embodiment 3 phenylpropanoids
The present embodiment provides a kind of preparation method of phenylpropanoids shown in formula I, comprises the steps:
S1. take Flemingia macrophylla 60kg, with root as raw material, be dried, be cut into small pieces.The alcohol reflux of 7 times amount 70% carries
Take 4 times, each 3 hours, extracting solution is merged, is concentrated into without alcohol taste, obtains extractum standby；
S2. the extractum after concentrating in step S1 is dissolved in 8L water, uses D101 macroporous adsorptive resins to wash it
De-, eluant is ethanol and the volume ratio of water is 10:90,3 column volumes of eluting, collects eluent, and named MM-1 is standby；
S3. with anti-phase ODS column chromatography, the flow point MM-1 collected in step S2 being carried out eluting, eluant is methanol-water
System, its volume ratio is 30:70,18 column volumes of eluting, collects the eluent of a flow point by every 3 column volumes, in order
Collect 6 flow points, be respectively designated as: MM-11, MM-12, MM-13, MM-14, MM-15, MM-16 are standby；
S4. by the flow point MM-12 collected in step S3 with preparing liquid phase separation, preparative liquid chromatography post is: YMC,
20mm*250mm, flow velocity: 10ml/min, flowing is methanol-water-acetic acid system mutually, methanol: water: the volume ratio of acetic acid is 30:
70:0.01, collects eluent by peak sequence, collects 7 flow points altogether, be respectively designated as MM-121, MM-122, MM-123, MM-
124, MM-125, MM-126, MM-127, standby；
S5. being purified with preparing liquid phase by the flow point MM-126 collected in step S4, preparative liquid chromatography post is: YMC,
20mm*250mm, flow velocity: 5ml/min, flowing is methanol-water-acetic acid system mutually, methanol: water: the volume ratio of acetic acid is 15:85:
0.01, collect eluent, after recrystallization, obtain described phenylpropanoids.
The preparation of embodiment 4 phenylpropanoids
The present embodiment provides a kind of preparation method of phenylpropanoids shown in formula I, comprises the steps:
S1. take Flemingia macrophylla 50kg, with root as raw material, be dried, be cut into small pieces.The alcohol reflux of 8 times amount 60% carries
Take 2 times, each 1.5 hours, extracting solution is merged, is concentrated into without alcohol taste, obtains extractum standby；
S2. the extractum after concentrating in step S1 is dissolved in 6L water, uses D101 macroporous adsorptive resins to wash it
De-, eluant is ethanol and the volume ratio of water is 5:95,3 column volumes of eluting, collects eluent, and named MM-1 is standby；
S3. with anti-phase ODS column chromatography, the flow point MM-1 collected in step S2 being carried out eluting, eluant is methanol-water
System, its volume ratio is 25:75,18 column volumes of eluting, collects the eluent of a flow point by every 3 column volumes, in order
Collect 6 flow points, be respectively designated as: MM-11, MM-12, MM-13, MM-14, MM-15, MM-16 are standby；
S4. by the flow point MM-12 collected in step S3 with preparing liquid phase separation, preparative liquid chromatography post is: YMC,
20mm*250mm, flow velocity: 10ml/min, flowing is methanol-water-acetic acid system mutually, methanol: water: the volume ratio of acetic acid is 25:
75:0.01, collects eluent by peak sequence, collects 7 flow points altogether, be respectively designated as MM-121, MM-122, MM-123, MM-
124, MM-125, MM-126, MM-127, standby；
S5. being purified with preparing liquid phase by the flow point MM-126 collected in step S4, preparative liquid chromatography post is: YMC,
20mm*250mm, flow velocity: 5ml/min, flowing is methanol-water-acetic acid system mutually, methanol: water: the volume ratio of acetic acid is 15:85:
0.01, collect eluent, after recrystallization, obtain described phenylpropanoids.
The preparation of embodiment 5 phenylpropanoids
The present embodiment provides a kind of preparation method of phenylpropanoids shown in formula I, comprises the steps:
S1. take Flemingia macrophylla 50kg, with root as raw material, be dried, be cut into small pieces.The alcohol reflux of 8 times amount 80% carries
Take 2 times, each 1.5 hours, extracting solution is merged, is concentrated into without alcohol taste, obtains extractum standby；
S2. the extractum after concentrating in step S1 is dissolved in 6L water, uses D101 macroporous adsorptive resins to wash it
De-, eluant is ethanol and the volume ratio of water is 10:90,3 column volumes of eluting, collects eluent, and named MM-1 is standby；
S3. with anti-phase ODS column chromatography, the flow point MM-1 collected in step S2 being carried out eluting, eluant is methanol-water
System, its volume ratio is 28:72,18 column volumes of eluting, collects the eluent of a flow point by every 3 column volumes, in order
Collect 6 flow points, be respectively designated as: MM-11, MM-12, MM-13, MM-14, MM-15, MM-16 are standby；
S4. by the flow point MM-12 collected in step S3 with preparing liquid phase separation, preparative liquid chromatography post is: YMC,
20mm*250mm, flow velocity: 10ml/min, flowing is methanol-water-acetic acid system mutually, methanol: water: the volume ratio of acetic acid is 10:
90:0.01, collects eluent by peak sequence, collects 7 flow points altogether, be respectively designated as MM-121, MM-122, MM-123, MM-
124, MM-125, MM-126, MM-127, standby；
S5. being purified with preparing liquid phase by the flow point MM-126 collected in step S4, preparative liquid chromatography post is: YMC,
20mm*250mm, flow velocity: 5ml/min, flowing is methanol-water-acetic acid system mutually, methanol: water: the volume ratio of acetic acid is 15:85:
0.01, collect eluent, after recrystallization, obtain described phenylpropanoids.
Compound embodiment 1 to embodiment 5 prepared carries out mass spectrum, proton nmr spectra, carbon-13 nmr spectra
Detection, result proves that gained compound is: 4,5-pyranoid rings-1 ' alkene-2 '-glucosyl group-1 ', 3 '-dihydroxy-2-methoxy
Base-3-hydroxy benzoic acid.Its structural formula is as shown in formula I:
Its mass spectrum, proton nmr spectra, carbon-13 nmr spectra spectral data as follows:
HR-ESIMS shows [M+Na]+for m/z 453.1158, and in conjunction with nuclear-magnetism feature, can obtain molecular formula is C18H22O12, no
Saturation is 8.
1H-NMR(600MHz,CD3OD):6.14(s,1H),4.73(d,1H),4.71(t,1H),3.79(s,3H)3.00-
4.00(H-2'-6'),2.59(d,2H)。
13C-NMR(150MHz,CD3OD):154.6(C-1),153.3(C-2),131.4(C-4),115.6(C-5),
131.4(C-3),128.2(C-6),114.7(C-2'),104.8(C-1”),93.2(C-1')78.7(C-3'),76.8-61.2
(C-2”-6”),50.4(C-4')。
The preparation of embodiment 6 phenylpropanoids salt
The preparation of phenylpropanoids hydrochlorate:
To pH value 2-3, stirring, second is dripped by this phenylpropanoids methanol solution drips saturated hydrochloric acid under stirring
Nitrile, sucking filtration, it is dried to obtain white powder solid, is the hydrochlorate of phenylpropanoids.
The preparation of phenylpropanoids sulfonate:
Alkali metal is added in the reaction system containing this phenylpropanoids, solvent, sulfonic acid, neutral oil and accelerator
Hydroxide, add solvent, lower alcohol and kicker, be passed through carbon dioxide, isolated white powder solid, be benzene
The sulfonate of C prime compounds.
Phenylpropanoids potassium salt or the preparation of sodium salt:
KOH or NaOH being dissolved in ethanol is added in this phenylpropanoids, the lower heating reflux reaction of stirring, cold system
Room temperature, drips acetonitrile, sucking filtration, is dried to obtain white solid, is potassium salt or the sodium salt of phenylpropanoids under stirring.
The preparation of phenylpropanoids ammonium salt:
To pH value 9-11, stirring, second is dripped by this phenylpropanoids methanol solution drips saturated ammonia under stirring
Nitrile, sucking filtration, it is dried to obtain white solid, is the ammonium salt of phenylpropanoids.
The spectral data of above-claimed cpd salt:
Phenylpropanoids hydrochlorate: ESIMS shows m/z 466.89, nuclear-magnetism feature1H-NMR(600MHz,
CD3OD):1H-NMR(600MHz,CD3OD):6.17(s,1H),4.77(d,1H),4.70(t,1H),3.78(s,3H)3.00-
4.00(H-2'-6'),2.44(d,2H)。
Phenylpropanoids sulfonate: ESIMS is shown as m/z 494.27, nuclear-magnetism feature1H-NMR(600MHz,
CD3OD):1H-NMR(600MHz,CD3OD):6.17(s,1H),4.78(d,1H),4.89(t,1H),3.66(s, 3H)3.00-
4.00(H-2'-6'),2.51(d,2H)。
Phenylpropanoids potassium salt or sodium salt:
Potassium salt: ESIMS shows m/z 468.33, nuclear-magnetism feature1H-NMR(600MHz,CD3OD):1H-NMR(600MHz,
CD3OD):6.11(s,1H),4.69(d,1H),4.66(t,1H),3.73(s,3H)3.00-4.00(H-2'-6'),2.50(d,
2H)。
Sodium salt: ESIMS shows m/z 452.63, nuclear-magnetism feature1H-NMR(600MHz,CD3OD):6.17(s,1H),4.50
(d,1H),4.61(t,1H),3.40(s,3H)3.00-4.00(H-2'-6'),2.10(d,2H)。
Phenylpropanoids ammonium salt: ESIMS shows m/z 445.26, nuclear-magnetism feature1H-NMR(600MHz,CD3OD):1H-NMR(600MHz,CD3OD):6.18(s,1H),4.78(d,1H),4.46(t,1H),3.46(s,3H)3.00-4.00(H-
2'-6'),2.51(d,2H)。
Shown in the structural formula such as formula IV of above-mentioned phenylpropanoids salt～formula (VIII).
Wherein, formula IV is the phenylpropanoids hydrochlorate prepared, and formula (V) is the Phenylpropanoid Glycosides prepared
The one of which sulfonate of compounds, formula VI is the one of which potassium salt of the phenylpropanoids prepared, formula
(VII) the one of which sodium salt of the phenylpropanoids for preparing, formula (VIII) is the phenylpropanoids prepared
One of which ammonium salt.
Experimental example 7 application test
RAW 264.7 oxidative macrophage that LPS is induced by compound of the present invention and salt stress be with the shadow of inflammation
Ring.(in order in experimentation, record is convenient, below phenylpropanoids of the present invention is numbered: medicine MM-126,
The most heretofore described medicine MM-126 i.e. refers to phenylpropanoids shown in formula I of the present invention or it is pharmaceutically acceptable
Salt.)
1 materials and methods
1.1 medicines and instrument
Lipopolysaccharide (lipopolysaccharide, LPS), MTT is purchased from Sigma company；Mouse macrophage Raw264.7
Purchased from the refined cell bank in Hunan；PBS；DMEM high glucose medium, hyclone, penicillin and streptomycin；Full-automatic microplate reader；Constant temperature
CO2Incubator.
Mice IL-1β (IL-1-β) ELISA detection kit, lot number: 2014/06 (96T)；Little mIL6
(IL-6) ELISA detection kit, lot number: 2014/06 (96T)；Murine tumor necrosis factor-α (TNF-α) ELISA detects examination
Agent box, lot number: 2014/06 (96T)；Mouse nitrous oxide (NO) ELISA detection kit, lot number: 2014/10 (96T)；Mice
Hydroxyl radical free radical (OH) ELISA detection kit, lot number: 2014/10 (96T).
Prepared by 1.2 medicines
First dissolve with a small amount of DMSO, be then diluted to certain concentration with DMEM, make DMSO content in final concentration be less than
1‰。
1.3 cells are cultivated
Mouse macrophage Raw 264.7 be incubated at containing 10% heat inactivation (56 DEG C, 30min) hyclone (FBS),
10U/mL penicillin sodium, 100 μ g/mL streptomycins DMEM culture medium in, 37 DEG C, 5%CO2Constant incubator is hatched growth.
1.4 cell viabilities measure
Cell viability is measured by mtt assay.Cell is made cell suspension inoculation incubate in 96 orifice plates (1 × 104/hole)
Educating 24h, resynchronization 24h, then the medicine of variable concentrations is acted on cell 2h, then adding LPS (30 μ g/mL) stimulates
24h, inhales and abandons former culture medium, and every hole adds the MTT (0.5mg/mL) of 100 μ L and continues to hatch 4h, inhales and abandons culture medium, and every hole adds
The DMSO of 150 μ L, shaking table shaking 10min, measure absorbance at 490nm.
1.5 NO assays
Raw 264.7 cell is inoculated in 96 orifice plate 24h, resynchronization 24h, is then acted on carefully by the medicine of variable concentrations
Born of the same parents 2h, then adding LPS (30 μ g/mL) stimulates 24h, finally collects supernatant, and is centrifuged 5min in 10000rpm, on subpackage
It is placed in clearly-80 DEG C to save backup.By mice NO kit measurement NO content.
1.6 inflammatory factor TNF-α, IL-1 β, IL-6 measure
Sample takes 1.5 samples prepared for subsequent inflammation factor determination.Cell generation TNF-α, IL-1 β, IL-6's
Amount is by mice TNF-α, and IL-1 β, IL-6 test kit measures.
1.7 OH assays
Sample takes 1.5 samples prepared for OH factor determination.By OH kit measurement content.
1.8 statistical analysis
Using SPSS17.0 software, experimental data is so that (x ± s represents；The data obtained is by with one factor analysis of variance, square
Difference homogeneous LSD checks, and heterogeneity of variance Dunnett T3 checks.
2 experimental results
2.1 cell viability
The impact of cell viability is evaluated by medicine by mtt assay.As it is shown on figure 3, medicine MM-126 is at 1.75-15.75 μ
In g/mL concentration range, Raw 264.7 cell viability is had no significant effect；Therefore the drug level pair under this range of concentrations
It is suitable in subsequent experimental.
The generation of 2.2 Drug inhibition NO
As shown in Figure 4, by LPS stimulate Raw 264.7 cell, its produce NO (65.81 ± 2.93IU/mL) content with
Normal group NO (33.61 ± 2.19IU/mL) compares significantly raised (p ＜ 0.01).Medicine MM-126 is at concentration (8.75-15.75 μ
G/mL) the NO content in the range of caused LPS raises obvious inhibitory action, and shows obvious dose-dependence.
2.3 Drug inhibition TNF-α, the generation of IL-1 β, IL-6
As shown in Figures 5 to 7, Raw 264.7 cell, Raw 264.7 cellular inflammation factor TNF-α are stimulated by LPS
(132.16 ± 5.28pg/mL), IL-1 β (358.80 ± 24.64pg/mL), IL-6 (198.39 ± 5.97pg/mL) content with just
Often organize TNF-α (65.41 ± 6.29pg/mL), IL-1 β (172.67 ± 10.06pg/mL), IL-6 (103.34 ± 2.88pg/mL)
Compare content significantly raised (p ＜ 0.01)；Illustrate that LPS can stimulate Raw 264.7 cell to produce a large amount of inflammatory factors.
LPS is stimulated Raw 264.7 cell to produce inflammation in the range of concentration (8.75-15.75 μ g/mL) by medicine MM-126
Factor TNF-α, IL-1 β, IL-6 content all has obvious inhibitory action (p ＜ 0.05), and shows obvious dose-dependant pass
System.
The generation of 2.4 Drug inhibition OH
As shown in Figure 8, by LPS stimulate Raw 264.7 cell, its produce OH (113.58 ± 6.03ng/mL) content with
Normal group OH (63.40 ± 1.19ng/mL) compares significantly raised (p ＜ 0.01).
The OH changes of contents that LPS is caused in the range of concentration (5.25-15.75 μ g/mL) by medicine MM-126 has significantly
Inhibitory action (p ＜ 0.05), and show dose-dependence.
This experiment, through In vitro culture, have studied medicine MM-126 to mouse macrophage NO, TNF-α, IL-1 β, IL-6, OH
The impact generated.
Medicine MM-126 need to be when middle and high concentration to NO, TNF-α, and the content of IL-1 β, IL-6 has obvious inhibition, says
Bright its plays anti-inflammatory activity needs higher drug concentration to realize；It is obvious to the inhibitory activity of OH, illustrates that it has certain antioxygen
Change activity.
Embodiment 8
The preparation of tablet: first prepare the phenylpropanoids shown in formula I as embodiment 1 method, and utilize this change
Compound and mineral acid (example hydrochloric acid, hydrobromic acid, Fluohydric acid., hydroiodic acid, sulphuric acid, nitric acid, carboxylic acid, phosphoric acid, lactic acid) or sulfonic acid or alkali
The salt that the hydroxide (such as potassium hydroxide, sodium hydroxide, calcium hydroxide, magnesium hydroxide, Lithium hydrate) of metal or ammonium are made, presses
This compound or its any one salt add excipient, pelletizing press sheet with excipient weight than the ratio for 1:10.
Embodiment 9
The preparation of powder: first prepare the phenylpropanoids shown in formula I as embodiment 1 method, and utilize this change
Compound and mineral acid (example hydrochloric acid, hydrobromic acid, Fluohydric acid., hydroiodic acid, sulphuric acid, nitric acid, carboxylic acid, phosphoric acid, lactic acid) or sulfonic acid or alkali
The salt that the hydroxide (such as potassium hydroxide, sodium hydroxide, calcium hydroxide, magnesium hydroxide, Lithium hydrate) of metal or ammonium are made, presses
Conventional powder preparation method makes powder.
Embodiment 10
Capsule or the preparation of granule: first prepare the phenylpropanoids shown in formula I as embodiment 1 method, with
And utilize this compound and mineral acid (example hydrochloric acid, hydrobromic acid, Fluohydric acid., hydroiodic acid, sulphuric acid, nitric acid, carboxylic acid, phosphoric acid, lactic acid)
Or sulfonic acid or alkali-metal hydroxide (such as potassium hydroxide, sodium hydroxide, calcium hydroxide, magnesium hydroxide, Lithium hydrate) or ammonium
The salt made, adds excipient with excipient weight than the ratio for 1:10 in this compound or its any one salt, makes glue
Wafer or granule.
Embodiment 11
The preparation of injection: first prepare the phenylpropanoids shown in formula I as embodiment 1 method, and utilization should
Compound and mineral acid (example hydrochloric acid, hydrobromic acid, Fluohydric acid., hydroiodic acid, sulphuric acid, nitric acid, carboxylic acid, phosphoric acid, lactic acid) or sulfonic acid or
The salt that alkali-metal hydroxide (such as potassium hydroxide, sodium hydroxide, calcium hydroxide, magnesium hydroxide, Lithium hydrate) or ammonium are made,
Water for injection routinely, fine straining, injection is made in embedding sterilizing.
Embodiment 12
A kind of pharmaceutical composition, prepares the phenylpropanoids shown in formula I containing embodiment 1 method, and utilizes
This compound and mineral acid (example hydrochloric acid, hydrobromic acid, Fluohydric acid., hydroiodic acid, sulphuric acid, nitric acid, carboxylic acid, phosphoric acid, lactic acid) or sulfonic acid
Or alkali-metal hydroxide (such as potassium hydroxide, sodium hydroxide, calcium hydroxide, magnesium hydroxide, Lithium hydrate) or ammonium make
Salt, and the powder that Radix Rosae Laevigatae, Fructus Zanthoxyli Dissiti, Caulis Spatholobi, Caulis Mahoniae, Herba Andrographis, Radix Angelicae Sinensis, Radix Codonopsis are made, and adjuvant.
Embodiment 13
A kind of pharmaceutical composition, prepares the phenylpropanoids shown in formula I, and Fructus Rosae Laevigatae containing embodiment 1 method
The powder that root, Fructus Zanthoxyli Dissiti, Caulis Spatholobi, Caulis Mahoniae, Herba Andrographis, Radix Angelicae Sinensis, Radix Codonopsis are made, and adjuvant.
Embodiment 14
A kind of pharmaceutical composition, prepares the phenylpropanoids shown in formula I, and Fructus Rosae Laevigatae containing embodiment 1 method
Root, Fructus Zanthoxyli Dissiti, Caulis Spatholobi, Caulis Mahoniae, Herba Andrographis, Radix Angelicae Sinensis, the extract of Radix Codonopsis, and adjuvant.Extract is by patent announcement number
CN1078079C、CN1170549C、CN1158087C、CN1330335C、CN1296071C、CN1321631C、CN1296072C、
In any one of CN1296073C or several patent documents, extracting method prepares.
Embodiment 15
A kind of pharmaceutical composition, prepares the phenylpropanoids shown in formula I containing embodiment 1 method, and utilizes
This compound and mineral acid (example hydrochloric acid, hydrobromic acid, Fluohydric acid., hydroiodic acid, sulphuric acid, nitric acid, carboxylic acid, phosphoric acid, lactic acid) or sulfonic acid
Or alkali-metal hydroxide (such as potassium hydroxide, sodium hydroxide, calcium hydroxide, magnesium hydroxide, Lithium hydrate) or ammonium make
Salt, and Radix Rosae Laevigatae, Fructus Zanthoxyli Dissiti, Caulis Spatholobi, Caulis Mahoniae, Herba Andrographis, Radix Angelicae Sinensis, the extract of Radix Codonopsis, and adjuvant.Extract be by
Patent announcement CN1078079C, CN1170549C, CN1158087C, CN1330335C, CN1296071C, CN1321631C,
In any one of CN1296072C, CN1296073C or several patent documents, extracting method prepares.
The ultimate principle of the present invention and principal character and the advantage of the present invention have more than been shown and described.The technology of this area
Personnel, it should be appreciated that the present invention is not restricted to the described embodiments, simply illustrating this described in above-described embodiment and description
The principle of invention, without departing from the spirit and scope of the present invention, the present invention also has various changes and modifications, and this is to this
Being apparent from for skilled person, these changes and improvements both fall within scope of the claimed invention.This
Bright claimed scope is defined by appending claims and equivalent thereof.
Claims (10)
1. a phenylpropanoids and pharmaceutically acceptable salt answering in the medicine of preparation treatment diseases associated with inflammation thereof
With, the structural formula of described phenylpropanoids is as shown in formula I:
Apply the most according to claim 1, it is characterised in that be content or the suppression suppressing cellular inflammation factor NO in preparation
Cellular inflammation factor TNF-α, the application in the medicine of the expression of IL-1 β, IL-6 or the activity of suppression hydroxyl radical free radical.
Apply the most according to claim 1, it is characterised in that described diseases associated with inflammation is cervicitis, endometritis, pelvic cavity
Inflammation, mastitis, pharyngolaryngitis and/or arthritis.
4. according to the application described in any one of claims 1 to 3, it is characterised in that described pharmaceutically acceptable salt is formula I
The pharmaceutically acceptable salt that shown phenylpropanoids is formed with acid or alkali,
The structure of described phenylpropanoids pharmaceutically acceptable salt is as shown in formula II or formula III:
Wherein, R is mineral acid, R1Or R2Or R3For any one in sulfonate radical, alkali metal ion or ammonium root or any two kinds or
Any three kinds.
Apply the most according to claim 4, it is characterised in that described mineral acid be hydrochloric acid, hydrobromic acid, Fluohydric acid., hydroiodic acid,
Sulphuric acid, nitric acid, carboxylic acid, phosphoric acid or lactic acid；Described sulfonate radical is the sulfonate radical with aryl；Described alkali metal ion be potassium from
Son, sodium ion, calcium ion, magnesium ion or lithium ion.
Apply the most according to claim 5, it is characterised in that described in have the sulfonate radical of aryl be benzenesulfonic acid root or to toluene
Sulfonate radical.
7. apply according to described in any one of claims 1 to 3, it is characterised in that described medicine contains the adjuvant pharmaceutically allowed
And/or carrier.
Apply the most according to claim 7, it is characterised in that described medicine is possibly together with Radix Rosae Laevigatae, Fructus Zanthoxyli Dissiti, Caulis Spatholobi, merit
One or more in Lao Mu, Herba Andrographis, Radix Angelicae Sinensis, Radix Codonopsis.
Apply the most according to claim 7, it is characterised in that described medicine is possibly together with Radix Rosae Laevigatae, Fructus Zanthoxyli Dissiti, Caulis Spatholobi, merit
The extract of one or more in Lao Mu, Herba Andrographis, Radix Angelicae Sinensis, Radix Codonopsis.
Apply the most according to claim 7, it is characterised in that the dosage form of described medicine is tablet, capsule, powder, granule
Agent, pill, solution, suspensoid, syrup, injection, ointment, suppository or spray.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610153535.1A CN106074583B (en) | 2016-03-17 | 2016-03-17 | A kind of application of phenylpropanoids and its pharmaceutically acceptable salt in the drug for preparing treatment diseases associated with inflammation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610153535.1A CN106074583B (en) | 2016-03-17 | 2016-03-17 | A kind of application of phenylpropanoids and its pharmaceutically acceptable salt in the drug for preparing treatment diseases associated with inflammation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106074583A true CN106074583A (en) | 2016-11-09 |
| CN106074583B CN106074583B (en) | 2018-09-25 |
Family
ID=58702335
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610153535.1A Active CN106074583B (en) | 2016-03-17 | 2016-03-17 | A kind of application of phenylpropanoids and its pharmaceutically acceptable salt in the drug for preparing treatment diseases associated with inflammation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106074583B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101235059A (en) * | 2008-02-29 | 2008-08-06 | 重庆市中药研究院 | Phenylpropanoids derivatives, preparation method thereof and medical composition using the same as active component |
| JP2012219056A (en) * | 2011-04-07 | 2012-11-12 | Hiroshima Univ | External preparation for skin |
| CN104274578A (en) * | 2014-09-05 | 2015-01-14 | 株洲千金药业股份有限公司 | Traditional Chinese medicinal composition with antimicrobial and antiinflammation effects and preparation method thereof |
-
2016
- 2016-03-17 CN CN201610153535.1A patent/CN106074583B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101235059A (en) * | 2008-02-29 | 2008-08-06 | 重庆市中药研究院 | Phenylpropanoids derivatives, preparation method thereof and medical composition using the same as active component |
| JP2012219056A (en) * | 2011-04-07 | 2012-11-12 | Hiroshima Univ | External preparation for skin |
| CN104274578A (en) * | 2014-09-05 | 2015-01-14 | 株洲千金药业股份有限公司 | Traditional Chinese medicinal composition with antimicrobial and antiinflammation effects and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 李华等: "千斤拔化学成分研究", 《中草药》 * |
| 陈一等: "千斤拔的镇痛和抗炎作用", 《广西医学》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106074583B (en) | 2018-09-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105663150B (en) | A kind of application of phenylpropanoids and its pharmaceutically acceptable salt in the drug for preparing treatment diseases associated with inflammation | |
| CN105708845B (en) | A kind of application of phenylpropanoids and its pharmaceutically acceptable salt in the drug for preparing treatment diseases associated with inflammation | |
| CN106046072B (en) | Phenylpropanoids and its pharmaceutically acceptable salt and pharmaceutical composition | |
| CN105777821B (en) | Phenylpropanoids and its pharmaceutically acceptable salt and pharmaceutical composition | |
| CN105732736B (en) | A kind of preparation method of phenylpropanoids | |
| CN106074579B (en) | A kind of application of phenylpropanoids in the drug for preparing treatment diseases associated with inflammation | |
| CN102961415B (en) | Phellinus lonicericola or the purposes of its extract | |
| CN106074583B (en) | A kind of application of phenylpropanoids and its pharmaceutically acceptable salt in the drug for preparing treatment diseases associated with inflammation | |
| CN105687217B (en) | A kind of application of phenylpropanoids and its pharmaceutically acceptable salt in the drug of preparation treatment diseases associated with inflammation | |
| CN106046071B (en) | A kind of preparation method of phenylpropanoids | |
| CN105663149B (en) | A kind of application of phenylpropanoids and its pharmaceutically acceptable salt in the drug for preparing treatment diseases associated with inflammation | |
| CN105884841B (en) | A kind of preparation method of phenylpropanoids | |
| TW382593B (en) | Hypoglycemic agents from harungana or vismia spp. | |
| CN105732737B (en) | A kind of phenylpropanoids and its pharmaceutical composition | |
| CN105601682B (en) | Phenylpropanoids and its pharmaceutically acceptable salt and pharmaceutical composition | |
| CN105669792B (en) | A kind of preparation method of phenylpropanoids | |
| CN105646613B (en) | Phenylpropanoids and its pharmaceutically acceptable salt and pharmaceutical composition | |
| CN105693789B (en) | A kind of preparation method of phenylpropanoids | |
| CN105646614B (en) | Phenylpropanoids and its pharmaceutically acceptable salt and pharmaceutical composition | |
| CN105582016B (en) | A kind of application of phenylpropanoids in the drug for preparing treatment diseases associated with inflammation | |
| CN105601681B (en) | A kind of preparation method of phenylpropanoids | |
| CN106046073B (en) | A kind of preparation method of phenylpropanoids | |
| CN105820197B (en) | A kind of phenylpropanoids and its pharmaceutical composition | |
| CN101367802A (en) | Beta-kabarin alkaloids in quassia wood, preparation method and application thereof | |
| US10329316B2 (en) | Phenylpropanoid compound and preparation method and use thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |