CN1742736A - Buckthorn extract, its preparing method and use in pharmaceutical process - Google Patents
Buckthorn extract, its preparing method and use in pharmaceutical process Download PDFInfo
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Abstract
The compound extracted from sallow thron berry includes four kinds, in which three kinds are active compounds. The sallow thron berry extract and its salt, enatiomorph, racemic body, tautomer or physiological function derivative can be used for preparing medicine for curing or preventing inflammatory diseases. It also can be used for preparing health-care food, beverage or feed.
Description
Technical field
The present invention relates to Fructus Hippophae extract, relate in particular to three kinds of from Fructus Hippophae, extracting and have active chemical compound, its preparation method and the application in the preparation medicine thereof.
Background technology
Puzzlement people's daily inflammatory diseases comprises: arthritis, for example osteoarthritis, rheumatoid arthritis, rheumatoid spondylitis, gouty arthritis etc.; Inflammatory dermatosis, for example eczema, psoriasis, dermatitis etc.; Inflammatory ophthalmic, for example uveitis, conjunctivitis etc.; Pulmonary disease, for example asthma, bronchitis, acute respiratory distress syndrome etc.; Bacteremia, that toxin mass formed by blood stasis, aphthous ulcer, gingivitis, pancreatitis etc.; Gastroenteropathy, for example Crohn disease, atrophic gastritis, ulcerative colitis, abdominal inflammation, peptic ulcer, irritable bowel trace integration disease, the mucosal inflammation that for example causes or gastroenteropathy of causing by nonsteroidal antiinflammatory drug or the like by Helicobacter pylori infection.
About the mechanism of various inflammation pathogenic effects is: known body intracellular nitric oxide (NO) is the toxicant of mediated cell immunity and inflammation.Its precursor is L-arginine (L-arg), and one of 2 identical hydrogen atoms on the terminal guanidine radicals of L-arg generate NO under the effect of NO synzyme (NOS).At present isolated three kinds of dissimilar NOS, comprised endothelial NO synzyme (eNOS), neuron NO synzyme (nNOS) and induction type NO synzyme (iNOS).Known at present, macrophage, hepatocyte, smooth muscle cell, adenocarcinoma cell and epithelial cell all can be expressed iNOS.Some inflammatory cytokine and microbial product such as lipopolysaccharide (LPS) then can induce iNOS to express.INOS can be given expression to high activity in case quilt induces, and produces a large amount of NO.
Therefore, for a long time, people are devoted to seek the inhibitor of NO synzyme and treat associated inflammatory diseases.But these inhibitor are confined to the material of chemosynthesis mostly, and side effect is bigger.Do not see the report that from the natural Chinese medicinal herb plant, extracts the anti-inflammatory activity material in the prior art.
Because various inflammation perplex human beings'health life, the low antiinflammatory active compound of the determined curative effect of attempting development of new, few side effects, development cost that relevant scientist does one's utmost all the time for a long time.Intensification may be a good carrier of realizing this hope to the research of Chinese herbal medicine.
Fructus Hippophae (Hippophae rhamnoides L.) is the Elaeangnaceae plant that mainly is distributed in the Chinese Huanghe valley, and in China, the fruit of Fructus Hippophae is used for the treatment of cough with copious phlegm, dyspepsia, and abdominal pain due to retention of food, the blood stasis amenorrhea falls and pounces on congestive edema.(the Pharmacopoeia of the People's Republic of China one one of version (Chemical Industry Press, the 127th page) in 2005.
Because the plant amedica side effect is little, the cost of studying and producing is low, so find to have the active constituents of medicine of definite curative effect from Chinese herbal medicine, will be a desirable trial.
Summary of the invention
The purpose of this invention is to provide Fructus Hippophae extract, its extracting method and in the preparation treatment or prevent purposes in the medicine of relevant inflammatory diseases.
The chemical compound that the present invention extracts from Fructus Hippophae (1), (2), (3), (4) are represented with following formula respectively:
(2) in the chemical compound that extracts from Fructus Hippophae, (3), (4) are reactive compound; Combination in any and salt, enantiomer, racemic modification, tautomer or the physiology functional derivatives of reactive compound (4) or itself and (1), (2), (3) all have pharmaceutically active.
The present invention extracts reactive compound from Fructus Hippophae method comprises the steps:
1) extracting solution concentrating under reduced pressure, the drying of Fructus Hippophae behind acetone extraction obtains extract;
2) above-mentioned extract is extracted successively with normal hexane, chloroform, ethyl acetate, n-butyl alcohol; With the extracting solution concentrating under reduced pressure of chloroform, the extract that drying obtains chloroform;
3) extract of above-mentioned chloroform is used normal hexane and ethyl acetate mixed liquor, methanol and water mixed liquid eluting successively through chromatographic column;
4) to the above-mentioned eluent of collecting through the further separation and purification of high pressure liquid chromatography, obtain reactive compound.
In the said extracted method, reduce pressure, concentrate and preferably carry out at 40 degrees centigrade.In the said extracted method, the mobile phase of high pressure liquid chromatography is normal hexane: ethyl acetate: acetone=60: 35: 5.
The combination in any of the chemical compound that the present invention extracts from Fructus Hippophae (4) or itself and (1), (2), (3) or its pharmaceutically acceptable salt, enantiomer, racemic modification, tautomer or physiology functional derivatives can be used for treating or prevent to suppress NO and generate the medication preparation that activity is useful disease.
The reactive compound that the present invention extracts from Fructus Hippophae or its pharmaceutically acceptable salt, enantiomer, racemic modification, tautomer or physiology functional derivatives can be used for treating or preventing the medication preparation of inflammatory diseases.
Suitable salt comprises and salt organic and mineral acid or alkali formation.Pharmaceutically acceptable salt comprises and following acid formation: hydrochloric acid, hydrobromic acid, sulphuric acid, citric acid, tartaric acid, phosphoric acid, lactic acid, acetone acid, acetic acid, trifluoroacetic acid, succinic acid, oxalic acid, fumaric acid, maleic acid, butanone diacid, methanesulfonic acid, ethyl sulfonic acid, p-methyl benzenesulfonic acid, benzenesulfonic acid, isethionic acid.Pharmaceutically acceptable basic salt comprises ammonium salt, alkali metal salt such as sodium salt and potassium salt, alkali salt such as calcium salt and magnesium salt and the salt that forms with organic base such as dicyclohexylamine and N-methyl D-glycosamine.
The example of physiology functional derivatives comprises ester, amide, carbamate, preferred ester and amide.
Chemical compound of the present invention also can be advantageously and second kind of pharmaceutically active substances, the selective depressant drug combination of especially derivable epoxidase (COX-2) isozyme, concrete chemical compound provided by the invention or its pharmaceutically acceptable salt, enantiomer, racemic modification or tautomer and cox 2 inhibitor drug combination with treatment inflammation, inflammatory diseases and with inflammation relevant disease.
Inflammatory diseases and clinical disease comprise joint disease, particularly arthritis (rheumatoid arthritis for example, osteoarthritis), or gastroenteropathy is (as ulcerative colitis, gastritis, and the mucosal inflammation that causes of other infection, the enteropathy that causes by NSAID (non-steroidal anti-inflammatory drug)), pulmonary disease is (as becoming the poverty-stricken disease of human respiratory, asthma, cystic fibrosis, chronic obstructive disease of lung), heart disease (as myocarditis), nervous tissue's disease (as the multiple sclerosis disease), pancreatic diseases (as diabetes and complication), kidney disease (as glomerulonephritis), dermatosis is (as dermatitis, psoriasis, eczema, urticaria), ocular disease (as glaucoma), transplant organ disease (as rejection), inflammatory sequela behind many organ diseases (as systemic lupus erythematosus (sle)) and virus and the bacterial infection.
In addition, chemical compound provided by the invention can help to prevent or treatment and HIV infect relevant lymphocytic radioactivity sensitivity, reduction growth of tumor, tumor development, angiogenesis and the neoplasm metastasis of losing, increase tumor cell during the radiotherapy.
Chemical compound provided by the invention can also be used to prepare health food, beverage or feedstuff etc.
The present invention extracts in the Fructus Hippophae that the method for reactive compound is simple and practical, and the reactive compound structure of being extracted is clear and definite, and has definite NO and suppress to generate active, reaches antiphlogistic effect, does not have cytotoxicity.
The specific embodiment
Embodiment 1: the determining of the preparation of extract and compound structure
The Fructus Hippophae branch corium farinosum of 3.0kg is broken, add 80% acetone (acetone: water=8: 2) 10 liters, placed at room temperature 12 hours.Filter, obtain extract.Seabuckthorn Fruit after the extraction extracts with 80% acetone 10L once again, mixes with the extract that obtains before.Carry out at concentrating under reduced pressure under the condition that this solution is 40 ℃, obtain the brown powder extract of 929.8g.
Get powder wood extract 929.8g and be dissolved in the 3L water, use normal hexane, chloroform, ethyl acetate, each 2L of butanols then, extract successively.Extracting solution carries out concentrating under reduced pressure under 40 ℃ condition, the normal hexane layer obtains the 21.14g extract, and chloroform layer obtains the 29.34g extract, and ethyl acetate layer obtains the 37.12g extract, and n-butanol layer obtains the 180.23g extract, and water layer obtains 631.73 extracts.Extract is carried out NO respectively produce inhibition test (with reference to back compound test method).The suppression ratio of each extract is respectively: normal hexane layer 89.5%, and chloroform layer 90.3%, ethyl acetate layer 67.2%, n-butanol layer 24.6%, water layer 0.8%, according to MTT toxicity test method, the normal hexane layer shows toxicity.
Get chloroform extract 28.1g, (the pure medicine of Wako gel C-300 and light, 6.5 * 18cm) separate with silica gel column chromatography.Use normal hexane: ethyl acetate=100: 0, carried out eluting extraction in 98: 2,96: 4,92: 8,85: 15,80: 20,60: 40,20: 80,0: 100, merge same stream part, obtain 6 stream parts and get liquid.fr.1(1.3g)、fr.2(1.0g)、fr.3(2.0g)、fr.4(1.5g)、fr.5(2.8g)、fr.6(12.2g)。
(manufacturing of Fuji Silysia Chemical company, 100-200mesh, 5.5 * 15cm) separate fr.2 (1.0g) stream part with Chromatorex ODS chromatographic column, use methanol: water=90: 10, methanol solution eluting, merging same stream part gets 4 streams part (fr.2-1-fr.2-4) stream part.Fr.2-3 (0.23g) separates with the HPLC chromatographic column.The HPLC chromatographic column adopts Shiseido Silica SG80A (Shiseido company manufacturing, 10 * 250mm), mobile phase normal hexane: ethyl acetate=80: 20, flow velocity is 4ml/min (room temperature), monitor with Shodex RI-72 (differential detector), when retention time is 13 minutes and 2 seconds, take out the separating medium that shows peak.This separating medium is reduced pressure under 40 ℃ condition, concentrates, obtained chemical compound (1)-white, needle-shaped crystals (12.9mg).
Fr.3 (2.0g) stream part is separated with the HPLC chromatographic column.The HPLC chromatographic column adopts Shiseido Silica SG80A (Shiseido company manufacturing, 10 * 250mm), mobile phase normal hexane: ethyl acetate=70: 30, flow velocity is 4ml/min (room temperature), monitor with ShodexRI-72 (differential detector), when retention time is 8 minutes and 20 seconds, take out the separating medium that shows peak.This separating medium is reduced pressure under 40 ℃ condition, concentrates, obtain stream part 230mg.This stream part is separated with the HPLC chromatographic column once more.The HPLC chromatographic column adopts Capcell PAK C18 (Shiseido company manufacturing, 10 * 250mm), mobile phase methanol: water=95: 5, flow velocity are 4ml/min (room temperature), with UV (210nm) monitoring, when retention time is 10 minutes and 40 seconds, take out the separating medium that shows peak.This separating medium is reduced pressure under 40 ℃ condition, concentrates, obtained chemical compound (2)-white powder (24.9mg).
(manufacturing of Fuji Silysia Chemical company, 100-200mesh, 5.5 * 15cm) separate fr.4 (1.5g) stream part with Chromatorex ODS chromatographic column, use methanol: water=50: 50, methanol: water=70: 30, methanol: water=90: 10, methanol solution eluting, merging same stream part gets 9 streams part (fr.4-1-fr.4-9) stream part.Fr.4-1 (0.12g) stream part is separated with the HPLC chromatographic column.The HPLC chromatographic column adopts Capcell PAK C18 (Shiseido company manufacturing, 10 * 250mm), mobile phase methanol: water=35: 65, flow velocity are 4ml/min (room temperature), with UV (254nm) monitoring, when retention time is 13 minutes and 40 seconds, take out the separating medium that shows peak.This separating medium is reduced pressure under 40 ℃ condition, concentrates, obtained chemical compound (3)-yellow oily (12.8mg).Fr.4-6 (0.07g) stream part is separated with the HPLC chromatographic column.The HPLC chromatographic column adopts Shiseido Silica SG80A (Shiseido company manufacturing, 10 * 250mm), mobile phase normal hexane: ethyl acetate: acetone=60: 35: 5, flow velocity is 4ml/min (room temperature), monitor with UV (254nm), when retention time is 11 minutes and 13 seconds, take out the separating medium that shows peak.This separating medium is reduced pressure under 40 ℃ condition, concentrates, obtained chemical compound (4)-white powder (6.0mg).
Chemical compound (1), (2), (3) predicate the material of document record.Chemical compound (4) is not for there being the material of document record.
Embodiment 2: the structure of determining physical and chemical parameter and chemical compound
The character of chemical compound (4), molecular weight etc. see Table 1; Chemical compound (4)
13C-NMR,
1The data of H-NMR see Table 2.And finally determined the structural formula of allied compound by above data.
Table 1: character, molecular weight, UV, the IR of chemical compound (4)
| Chemical compound 4 | |
| Proterties HR-FAB-MS (m/z) calculated value measured value weight molecule formula UV λmaxnm(logε) IR v cm-1 max | Colourless powder 633.38057 633.37912 634 C 39H 54O 7 327(4.30) 300(4.26) 245(4.21) 3430(OH) 1695 1515 |
The NMR spectroscopic data of table 2 chemical compound 4 (ppm, in Methanol-d
4600MHz)
S: unimodal d: bimodal t: triplet m: multiplet
() value is Hz
| Position | δ H | δ C | Position | δ H | δ C |
| 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 | 2.03m，1.00m 5.04(ddd，11.8，10.0，4.4) 3.24(d，10.0) 0.93m 1.60m，1.48m 1.72m，1.51m 1.67m 1.98m，1.85m 5.24(t，3.8) 1.78m 2.00m，1.60m 2.84(dd，3.8，13.8) 1.66m，1.12m | 45.2 73.8 81.2 41.0 56.6 19.6 33.8 43.0 49.1 39.5 24.6 123.4 145.3 40.6 28.8 24.1 47.6 42.7 47.3 31.6 | 21 22 23 24 25 26 27 28 29 30 1′ 2′ 3′ 4′ 5′ 6′ 7′ 8′ 9′ | 1.38m，1.20m 1.36m，1.52m 1.06s 0.88s 1.09s 0.83s 1.17s 0.89s 0.94s 7.03(d，2.1) 6.77(d，8.6) 6.93(dd，2.1，8.6) 7.55(d，15.8) 6.27(d，15.8) | 34.9 33.8 29.2 17.4 16.9 17.7 26.4 181.8 33.5 24.0 127.9 115.2 146.6 149.5 115.9 122.8 146.8 116.5 169.3 |
The structural formula of chemical compound 4 is determined as follows:
Embodiment 3: suppress NO and generate test
The obstruction effect (effect that suppresses the NO generation) that stimulates the megalith phagocyte that produces that NO is generated owing to interferon r and lipopolysaccharide is tried to achieve by following experimental technique.And estimate the inhibition effect that NO generates according to the IC50 (um) that hinders effect.
Material therefor:
RAW 264.7 cells (big Japanese pharmacy)
N-1-hydrochloride naphthodiamide (the pure medicine of 1g and light)
Sulfanilamide (the pure medicine of 500g and light)
Ham ' s F12 culture medium (SIGMA N488 500mL)
IFN-γ(Geneyme/Techne 100μg)
Lipopolysaccharide (LPS, 055:B5 10mg, Sigma)
Phosphoric acid (the pure medicine of 500ml and light)
DMSO (the pure medicine of 500ml and light)
96 hole titer plate (50/ box Sumitomo Bakelite, trade name (8096R))
Test method:
The RAW264.7 cell is the CO 5%
2, 37 ℃ temperature, contain and cultivate in the culture medium of Ham ' s F12 of 10%FBS.The RAW264.7 cell concentration that will be in exponential phase is adjusted into 1.2 * 10
6Individual/ml, with cell at CO
2Cultivate after 2 hours in the calorstat.The extract or the segregation composition of various concentration have been added.Add LPS (100ng/ml) simultaneously, INF-γ (10U/ml), a corpse or other object for laboratory examination and chemical testing 0.4 μ L.At CO
2After cultivating a period of time in the calorstat, get culture supernatant, the culture supernatant 100 μ L of RAW264.7 cell are put in flat 96 orifice plates, with the oxysome NO of Griess standard measure NO
2 -The concentration of DMSO is become in culture medium below 0.2%, add 0.1% naphthylenediamine solution, 50 μ L, 1% P-aminobenzene-sulfonamide solution, 50 μ L, black out was placed 10 minutes in the room temperature.0.D. with spectrophotometric determination 570nm, (contrast 655nm).According to NaNO
2The inspection amount line that standard solution makes, the NO in the quantitative culture medium
2 -
Cytotoxicity is by mtt assay, definite by microscopy.Mtt assay is known conventional method.That is, in 96 hole titer plate, every hole 200 μ l cell concentrations are 1.0 * 10
5Cell/ml adds the extract or the monomer component of variable concentrations, with cell culture 16 hours, adds MTT reagent, cultivates 4 hours again.Abandon supernatant, add 150 μ LDMSO, dissolve fully, measure the absorbance under the 570nm generating De Jia Za (formazane).
Activity rating
Calculate NO
2 -Amount, the formula below the substitution is obtained the inhibition effect
Suppression ratio (%)={ 1-(X-Y)/(Z-Y) } * 100
X: in the presence of experimental compound, induce the NO of generation by IFN-γ and LPS
2 -Amount,
Y; Under all non-existent situation of experimental compound, IFN-γ and LPS, induce the NO of generation
2 -Amount,
Z:IFN-γ and LPS induce the NO of generation
2 -Amount.
The NO of chemical compound (4) generates the IC that suppresses effect
50As follows:
Table 3 generates from the isolated single product compound oxidation nitrogen of Fructus Hippophae and suppresses experimental result
| Chemical compound | Suppression ratio (IC 50 M) |
| 2 | 40.2 |
| 3 | 24.8 |
| 4 | 7.6 |
Embodiment 4: atomic group deactivation experiment
Atomic group deactivation experiment is with the method for Okada etc., carry out as follows: in 96 orifice plate (Sumitomo Bakelite systems, #8096 R) adds 0.2M acetate buffer solution (pH5.5) 40 μ L, 12% aqueous acetaldehyde solution, 120 μ L in, adds with the dissolved experimental compound 0.4 μ L of dimethyl sulfoxine, add 0.5mM DPPH solution 40 μ L again, in the darkroom, placed 30 minutes.Afterwards, measure the absorbance of 520nm with photographic plate reader (Bio-Rad system 3550).
Inactivation ratio (%)={ 1-(X-Z)/(Y-Z) } * 100
X: the absorbance when having added experimental compound
Y: the absorbance when not adding experimental compound
Z: the absorbance when having only dimethyl sulfoxine and 12% formalin
Table 4 is from the isolated chemical compound atomic group of Fructus Hippophae deactivation result of experiment
| Chemical compound | Suppression ratio (IC 50 M) |
| 2 | ＞100 |
| 3 | 55.0 |
| 4 | 34.7 |
Embodiment 5: the preparation pharmaceutical dosage form
When chemical compound provided by the invention or its pharmaceutically acceptable salt, enantiomer, racemic modification, tautomer or physiology functional derivatives are individually dosed, preferably provide with pharmaceutical formulation, said preparation comprises when chemical compound (1) or its pharmaceutically acceptable carrier of its pharmaceutically acceptable salt, enantiomer, racemic modification, tautomer or physiology functional derivatives or excipient and optional one or more other treatment composition.
Described preparation comprises oral Preparation, parenteral preparation (comprising intradermal injection, intramuscular injection, intravenous injection and intraarticular injection), sucks preparation (comprising the microgranule powder or the mist agent that produce by in the pressurization aerosolizer of various dose, aerosol apparatus, the insufflator), rectum and local administration preparation (comprising percutaneous drug delivery, oral administration, sublingual administration, eye drops).Optimal route of administration depends on medication patient's situation and disease.Preparation provides with unit dosage forms usually, and can be prepared by known any method in the pharmaceutical field.All methods comprise that all carrier is made of one or more auxiliary elements with active ingredient and the blended step of carrier.Generally, as required described product is made preparation subsequently by active component and liquid or fine solid carrier or both are evenly combined closely; The preparation of the present invention of suitable for oral administration administration can provide with independently unit such as capsule, cachet or tablet, and per unit contains the active component of scheduled volume; Powder or granule; Water-soluble liquid or suspension; Or oil-in-water emulsion or water-in-oil emulsion; Also can be bolus, electuary or paste.
Can prepare tablet by optional with one or more auxiliary element tablettings or plastotype; Can prepare compressed tablets by the active component in stranglehold liquid form such as powder or the granule on suitable machine (optional and binding agent, lubricant, inert diluent, surfactant or dispersant); Described tablet may optionally be coating or impression, and is made into slow release or the controlled release of preparation so that active component to be provided.
The preparation of parenteral comprises aqueous and non-aqueous aseptic parenteral solution, this injection can contain antioxidant, buffer agent, antibacterial and make preparation and solute that blood samples of patients etc. is opened, aqueous and nonaqueous sterile suspensions, this suspension can contain suspending agent and thickening agent; Described preparation can be with unit dose or multiple-unit container, for example cuts open pipe with the peace of sealing and glass tube vial provides; And can under cryodesiccated condition, store, only need provide aseptic liquid-carrier such as saline or water for injection before using certainly; Can use powder, granule and interim injection solution of previously described various preparation tablets and suspension.
The preparation of rectally can provide with the suppository form of common carrier (as cocoa butter or Polyethylene Glycol).
Preparation (as buccal or sublingual administration agent) is approximately given in the part that is used for the oral cavity, is included in the lozenge of the active ingredient in the flavoured base (as sucrose, arabinose).
Be appreciated that except that the top composition of mentioning especially, preparation of the present invention also comprises other conventional ingredient of this area related preparations type, for example is suitable for the flavoring agent of oral administration etc.
1. will mix with corn starch 40g from the chemical compound 10g that Fructus Hippophae is extracted, add water and make soft material, cross 12 mesh sieve pelletizes, drying, obtain granule, in this granule, contain chemical compound (1) 100mg among every 500mg.
2. will mix with lactose 100g, magnesium stearate 10g from the chemical compound 40g that Fructus Hippophae is extracted, fill enteric coated capsule with every 600mg, in this enteric coated capsule, each capsule contains chemical compound (1) 160mg.
The 3 chemical compound 25g that will extract from Fructus Hippophae are with common injection autofrettage, with the distilled water for injection 1000ml dissolving that is heated to 60 degrees centigrade, reconcile to wait with Nacl and open, and enclose peace and cut open bottle.Contain chemical compound (1) 250mg among this injection 10ml.
Embodiment 6: preparation food
Chemical compound provided by the invention also can provide with the form of food, and preferred food form comprises powder, granule, paste, jelly etc., and particle form can be added sugar (as lactose) and be increased sweet taste; Also can be prepared into the form of beverage; These foods or beverage can also add vitamin, inorganic elements except that the Fructus Hippophae extract, as calcium, alcohols, deodorant, as polyphenol.These foods comprise kinds such as special health food, medical food.
Claims (10)
1. extract in the Fructus Hippophae is comprising combination in any and salt, enantiomer, racemic modification, tautomer or the physiology functional derivatives of chemical compound (4) or itself and chemical compound (1), (2), (3); Chemical compound (1), (2) (3), (4) of extracting are represented with following formula respectively:
2. extract in the Fructus Hippophae according to claim 1, it is characterized in that, suitable salt comprises and salt organic and mineral acid or alkali formation that pharmaceutically acceptable salt comprises and following acid forms: hydrochloric acid, hydrobromic acid, sulphuric acid, citric acid, tartaric acid, phosphoric acid, lactic acid, acetone acid, acetic acid, trifluoroacetic acid, succinic acid, oxalic acid, fumaric acid, maleic acid, butanone diacid, methanesulfonic acid, ethyl sulfonic acid, p-methyl benzenesulfonic acid, benzenesulfonic acid, isethionic acid; Pharmaceutically acceptable basic salt comprises ammonium salt, alkali metal salt, as sodium salt and potassium salt, alkali salt such as calcium salt and magnesium salt and the salt that forms with organic base such as dicyclohexylamine and N-methyl D-glycosamine.
3. Fructus Hippophae extract according to claim 1 is characterized in that, the physiology official dirt thing that can spread out comprises ester, amide, carbamate, preferred ester and amide.
4. the extracting method of a Fructus Hippophae extract comprises the steps:
1) sour jujube branch corium farinosum is broken, the extracting solution concentrating under reduced pressure behind the acetone extraction, drying obtain extract;
2) above-mentioned extract is extracted successively with normal hexane, chloroform, ethyl acetate, n-butyl alcohol; With the extracting solution concentrating under reduced pressure of chloroform, the extract that drying obtains chloroform;
3) extract of the above-mentioned chloroform in mountain is used normal hexane and ethyl acetate mixed liquor, methanol and water mixed liquid eluting successively through chromatographic column;
4) the above-mentioned eluent of collecting is further separated through high pressure liquid chromatography, concentrating under reduced pressure, drying obtain active compound.
5. according to the extracting method of the described Fructus Hippophae extract of claim 4, it is characterized in that concentrating under reduced pressure carries out at 40 degrees centigrade; The mobile phase of high pressure liquid chromatography is normal hexane: ethyl acetate: acetone=60: 35: 5.
6. according to the compositions of the described Fructus Hippophae extract of one of claim 1-3 or itself and second kind of pharmaceutically active substances, with the pharmaceutical preparation of pharmaceutically acceptable carrier or excipient preparation.
7. according to the described Fructus Hippophae extract of one of claim 1-3, the purposes in preparation treatment or prevention inflammatory diseases medicine.
8. according to the compositions of the described Fructus Hippophae extract of one of claim 1-3 and second kind of pharmaceutically active substances, the purposes in preparation treatment or prevention inflammatory diseases medicine.
9. according to claim 7 or the 8 described Fructus Hippophae extracts purposes in preparation treatment or prevention inflammatory diseases medicine, it is characterized in that, described inflammatory diseases and clinical disease comprise joint disease, particularly arthritis, for example rheumatoid arthritis, osteoarthritis; Or gastroenteropathy, the mucosal inflammation that causes as ulcerative colitis, gastritis and other infection, the intestinal disease that causes by NSAID (non-steroidal anti-inflammatory drug); Pulmonary disease is as becoming the poverty-stricken disease of human respiratory, asthma, cystic fibrosis, chronic obstructive disease of lung; Heart disease is as myocarditis; Nervous tissue's disease such as multiple sclerosis disease; Pancreatic diseases is as diabetes and complication; , the kidney disease, as glomerulonephritis; Dermatosis is as dermatitis, psoriasis, eczema, urticaria; Ocular disease is as glaucoma; The transplant organ disease is as rejection; Many organ diseases are as the inflammatory sequela behind systemic lupus erythematosus (sle) and virus and the bacterial infection.
10. described from Fructus Hippophae extract according to one of claim 1-3, the application in preparation health food, beverage or feedstuff.
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| JPWO2019168185A1 (en) * | 2018-03-02 | 2021-02-18 | ロート製薬株式会社 | Food composition for prevention and / or risk reduction of posterior ocular abnormalities |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US6399116B1 (en) * | 2000-04-28 | 2002-06-04 | Rulin Xiu | Rhodiola and used thereof |
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| CN104018343A (en) * | 2014-06-06 | 2014-09-03 | 保琦蓓 | Hemp bast fiber extract with antibacterial activity, preparation method and application of hemp bast fiber extract |
| CN104018343B (en) * | 2014-06-06 | 2016-03-02 | 保琦蓓 | A kind of Chinese fiber crops bast fiber extract, preparation method and its usage with antibacterial activity |
| CN106727007A (en) * | 2017-01-02 | 2017-05-31 | 李大兴 | A kind of sea-buckthorn anti-aging toothpaste |
| JPWO2019168185A1 (en) * | 2018-03-02 | 2021-02-18 | ロート製薬株式会社 | Food composition for prevention and / or risk reduction of posterior ocular abnormalities |
| JP7304585B2 (en) | 2018-03-02 | 2023-07-07 | ロート製薬株式会社 | Food composition for prevention and/or risk reduction of posterior segment abnormality |
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