CN104016863A - V-type crystal of chlorogenic acid and preparation method of V-type crystal as well as application of V-type crystal in medicinal compositions or health products - Google Patents
V-type crystal of chlorogenic acid and preparation method of V-type crystal as well as application of V-type crystal in medicinal compositions or health products Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/732—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids of unsaturated hydroxy carboxylic acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
- C07C67/52—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
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Abstract
The invention relates to a V-type crystal of chlorogenic acid and a preparation method of the V-type crystal and application of the V-type crystal in medical compositions and health products. The invention also relates to application of the medical compositions or health products containing the crystal, as well as application of the crystal in preparation of medicaments for resisting oxidation, cleaning free radicals, improving central excitation, expanding heart and blood vessels, protecting liver and gallbladder, resisting tumors and human immunodeficiency virus, sterilizing and diminishing inflammation or resisting allergy.
Description
Technical field
The present invention relates to the V-type crystal of chlorogenic acid and its preparation method, also relate to the pharmaceutical composition or the healthcare products that comprise it, with and anti-oxidant in preparation, remove free radical, improve central excitation, expanding cardiovascular, hepatic cholagogic, purposes in antitumor, anti AIDS virus, antisepsis and anti-inflammation or antianaphylactic pharmaceutical composition or healthcare products.
Background technology
The structural formula of chlorogenic acid (chemical name: CA, English name: Chlorogenic acid) is as follows:
In Chinese patent CN1181042C, record " extracting and purifying method of Chlorogenic Acid of Flos Lonicerae " of people's inventions such as Han Lujia.Wherein, related to a kind of extracting and purifying method of herbal medicine functional ingredient.
In Chinese patent CN1168698C, record " macroporous resin adsorption is extracted the processing method of chlorogenic acid in high content " of Liu Bin invention.Wherein, related to a kind of separating technology by Japanese Honeysuckle pulverizing, the extraction of chlorogenic acid aqueous extract and macroporous resin adsorption chlorogenic acid in high content.
In Chinese patent CN1435406A, record " a kind of method of preparing chlorogenic acid " of people's inventions such as Liu Shiming.Wherein, related to a kind of method of preparing chlorogenic acid, it belongs to a kind of extracting method of plants ' medicinal component.
In Chinese patent CN1568960A, record " high purity chlorogenic acid prescription " of the inventions such as Zhang Jie
[4].Wherein, related to a kind of medicine that pharmaceutically can be applicable to clinical various formulations of preparing taking high-purity chlorogenic acid as raw material.
In Chinese patent CN1616402A, record " a kind of chlorogenic acid extracts the method separating " of Tang Huazhao invention.Wherein, relate to a kind of chlorogenic acid and extracted the method, the particularly method of extraction from Folium Eucommiae, acer truncatum leaf, separation, purifying chlorogenic acid that separate.
In Chinese patent CN100494393C, record " technique for producing high purity chlorogenic acid in industrialization scale " of the people such as Zhang Jie, Zhang Liang invention.Wherein, related to the technique that a kind of high purity chlorogenic acid in industrialization scale is produced.
In Chinese patent CN101293832A, record " synthetic method of chlorogenic acid and derivative thereof " of people's inventions such as Zhao Yu.Wherein, related to the synthetic method of a kind of chlorogenic acid and derivative thereof.
In Chinese patent CN101302156A, record " a kind of extraction process of Hemp Eupatorium Content of Chlorogenic Acid " of people's inventions such as Cao's col journey.Wherein, related to a kind of extraction process of Hemp Eupatorium Content of Chlorogenic Acid.
In Chinese patent CN101314568A, record " a kind of novel method of adsorption separation of high purity chlorogenic acid " of the inventions such as Lu Dingqiang.Wherein, related to a kind of novel method of adsorption separation of high purity chlorogenic acid.
In Chinese patent CN101367729A, record " a kind of method of complexation purification by liquid extraction of chlorogenic acid " of the invention such as Lu Dingqiang, Wang Jun.Wherein, related to a kind of method of utilizing Complexation Extraction Technique purification chlorogenic acid.
In Chinese patent CN101503356A, record " a kind of novel method of preparing high-purity chlorogenic acid " of the people such as Lu Dingqiang, Zhao Hui invention.Wherein, related to a kind of novel method of preparing high-purity chlorogenic acid.
In Chinese patent CN101704748A, record " a kind of extracting method of chlorogenic acid " of people's inventions such as Liu Dongfeng.Wherein, related to a kind of cost low, output is large, and the cycle is short, is easy to realize the method for industrialized separating-purifying chlorogenic acid.
Summary of the invention
the problem that invention will solve
Research purpose of the present invention is: study from the existence of the crystal formation solid matter of chlorogenic acid, by crystal formation triage techniques, crystal formation evaluated biological activity technology, in the raw material aspect of active constituents of medicine, find and find crystal formation kind and the status flag of chlorogenic acid solid matter, and crystal formation research is combined with pharmacodynamic study, for the medicinal crystal-form solid matter of finding, finding, exploitation has the chlorogenic acid of optimal efficacy provides basic scientific research data; Meanwhile, also for providing scientific basis from chlorogenic acid solid crystal formation raw material basis application country or international intellecture property invention patent protection.
for the scheme of dealing with problems
The application provides a kind of V-type crystal of chlorogenic acid, it is characterized in that, when using powder X-ray diffractometry to adopt CuK
αwhen radiation experiments condition analysis, the peak position of height %=100% in 2 θ=17.7 ± 0.2 ° or
place, and have 1 disperse diffraction peak.
According to the V-type crystal of the chlorogenic acid described in the application, it is characterized in that when using when Infrared spectroscopy, described crystal 3388,2963,2627,1693,1632,1602,1522,1445,1362,1282,1182,1162,1117,1080,1040,977,914,881,853,813,783,734,714,657,603,571,553,530,509,448,427cm
-1place has diffuse reflectance infrared spectroscopy peak, and the permissible variation at its mid-infrared spectral behavior peak is ± 2cm
-1.
According to the V-type crystal of the chlorogenic acid described in the application, while it is characterized in that using dsc to analyze, be in the DSC collection of illustrative plates of 10 DEG C of per minutes at temperature rise rate, locate to have 1 endotherm(ic)peak at 212 DEG C ± 3 DEG C.
The application also provides a kind of mixing crystal-form substances of chlorogenic acid, it is characterized in that the chlorogenic acid V-type crystal described in the application who contains arbitrary proportion.
The application also provides the preparation method of the V-type crystal of the chlorogenic acid described in a kind of the application, it is characterized in that using acetone, methyl alcohol or ethanol chlorogenic acid raw material to be dissolved completely under 15 DEG C～80 DEG C temperature condition as single solvent, and prepare chlorogenic acid V-type crystal through 10 DEG C～80 DEG C of envrionment temperatures, ambient moisture 10%～75%, normal pressure or vacuum pressure condition.
The application also provides the preparation method of the V-type crystal of the chlorogenic acid described in a kind of the application, it is characterized in that, after using any two or more in methyl alcohol, ethanol, Virahol, chloroform, acetone, benzene, toluene or water to mix, at 15 DEG C～80 DEG C temperature, chlorogenic acid raw material is dissolved completely, and recrystallization under 4 DEG C～80 DEG C of envrionment temperatures, ambient moisture 10%～75%, normal pressure or vacuum pressure condition prepares chlorogenic acid V-type crystal.
The application also provides the preparation method of the V-type crystal of the chlorogenic acid described in a kind of the application, it is characterized in that, adopts scorification to prepare chlorogenic acid V-type crystal; Described scorification is that temperature more than 210 DEG C is by chlorogenic acid raw materials melt, then through-10 DEG C～50 DEG C cooling V-type crystal that prepare of envrionment temperature.
The application also provides a kind of pharmaceutical composition or healthcare products, it is characterized in that, V-type crystal and the pharmaceutically acceptable carrier of the chlorogenic acid described in the application who contains effective dose.
The application also provides a kind of pharmaceutical composition or healthcare products, it is characterized in that, mixing crystal-form substances and the pharmaceutically acceptable carrier of the chlorogenic acid described in the application who contains effective dose.
According to the pharmaceutical composition described in the application or healthcare products, the every daily dosage that it is characterized in that the V-type crystal of described chlorogenic acid is 2～1000mg, preferably 10～800mg.
According to the pharmaceutical composition described in the application or healthcare products, it is characterized in that described pharmaceutical composition or healthcare products are tablet, hard capsule, pill, powder injection, granule, sustained release preparation or controlled release preparation.
The V-type crystal that the application also provides the chlorogenic acid described in the application is anti-oxidant in preparation, remove free radical, improve central excitation, purposes in expanding cardiovascular, hepatic cholagogic, antitumor, anti AIDS virus, antisepsis and anti-inflammation or antianaphylactic pharmaceutical composition or healthcare products.
the effect of invention
The present invention develops a kind of V-type crystal of chlorogenic acid, and find when the V-type crystal of this chlorogenic acid is applied in pharmaceutical composition or healthcare products as activeconstituents, can fully ensure its Absorption Characteristics in vivo, effectively bioavailability, effective blood drug concentration, stablize lasting action time, thereby bring into play the effect of good prevention, treatment and health care.
Brief description of the drawings
Fig. 1 is the x-ray diffractogram of powder spectrum of embodiment 1 Content of Chlorogenic Acid V-type crystal prototype 1.
Fig. 2 is the infrared absorpting light spectra of embodiment 1 Content of Chlorogenic Acid V-type crystal prototype 1.
Fig. 3 is the DSC collection of illustrative plates of embodiment 1 Content of Chlorogenic Acid V-type crystal prototype 1.
Fig. 4 is the determination of plasma concentration result in rat body after embodiment 1 Content of Chlorogenic Acid V-type crystal prototype 1 oral absorption.
Embodiment
The V-type crystal of the application's chlorogenic acid, when using powder X-ray diffractometry to adopt CuK
αwhen radiation experiments condition analysis, the peak position of height %=100% in 2 θ=17.7 ± 0.2 ° or
place, and have 1 disperse diffraction peak.
When using when Infrared spectroscopy, described crystal 3388,2963,2627,1693,1632,1602,1522,1445,1362,1282,1182,1162,1117,1080,1040,977,914,881,853,813,783,734,714,657,603,571,553,530,509,448,427cm
-1place has diffuse reflectance infrared spectroscopy peak, and the permissible variation at its mid-infrared spectral behavior peak is ± 2cm
-1.
And the V-type crystal of described chlorogenic acid, in the time using dsc to analyze, is in the DSC collection of illustrative plates of 10 DEG C of per minutes at temperature rise rate, locates to have 1 endotherm(ic)peak at 212 DEG C ± 3 DEG C.
The application also provides a kind of mixing crystal-form substances of chlorogenic acid, it is characterized in that the chlorogenic acid V-type crystal described in the application who contains arbitrary proportion.
The application also provides a kind of preparation method of V-type crystal of described chlorogenic acid, it is characterized in that using acetone, methyl alcohol or ethanol chlorogenic acid raw material to be dissolved completely under 15 DEG C～80 DEG C temperature condition as single solvent, and prepare chlorogenic acid V-type crystal through 10 DEG C～80 DEG C of envrionment temperatures, ambient moisture 10%～75%, normal pressure or vacuum pressure condition.
The application also provides a kind of preparation method of V-type crystal of described chlorogenic acid, it is characterized in that, after using any two or more in methyl alcohol, ethanol, Virahol, chloroform, acetone, benzene, toluene or water to mix, at 15 DEG C～80 DEG C temperature, chlorogenic acid raw material is dissolved completely, and recrystallization under 4 DEG C～80 DEG C of envrionment temperatures, ambient moisture 10%～75%, normal pressure or vacuum pressure condition prepares chlorogenic acid V-type crystal.
The application also provides a kind of preparation method of V-type crystal of described chlorogenic acid, it is characterized in that, adopts scorification to prepare chlorogenic acid V-type crystal; Described scorification is that temperature more than 210 DEG C is by chlorogenic acid raw materials melt, then through-10 DEG C～50 DEG C cooling V-type crystal that prepare of envrionment temperature.
The application also provides a kind of pharmaceutical composition or healthcare products, it is characterized in that, mixing crystal-form substances and the pharmaceutically acceptable carrier of the chlorogenic acid described in V-type crystal or the application of the chlorogenic acid described in the application who contains effective dose.
In the pharmaceutical composition or healthcare products described in the application, the every daily dosage of the V-type crystal of described chlorogenic acid is 2～1000mg, preferably 10～800mg.
Pharmaceutical composition described in the application or healthcare products are tablet, hard capsule, pill, powder injection, granule, sustained release preparation or controlled release preparation preferably.
The V-type crystal that the application also provides the chlorogenic acid described in the application is anti-oxidant in preparation, remove free radical, improve central excitation, purposes in expanding cardiovascular, hepatic cholagogic, antitumor, anti AIDS virus, antisepsis and anti-inflammation or antianaphylactic pharmaceutical composition or healthcare products.
The application also provides a kind of active function that uses the brilliant V-type crystal of chlorogenic acid to make the most of the advantage in disease preventing and treating as the medicine of activeconstituents exploitation and pharmaceutical composition thereof and healthcare products, it is characterized in that using the chlorogenic acid V-type crystal containing described in the application as activeconstituents, ensured its Absorption Characteristics in vivo, effectively bioavailability, effective blood drug concentration, stablize the lasting time and reach prevention, treatment, health-care effect and the application of making the most of the advantage.
The present invention also provides a kind of biology sorption after using chlorogenic acid V-type crystal as medicine and pharmaceutical composition and the healthcare products oral administration of activeconstituents exploitation, it is characterized in that using the chlorogenic acid V-type crystal containing described in the application after 15 minutes, in blood, can reach fast by gi tract as activeconstituents peak concentration value also sustainable maintenance within 3 hours, play a role.
Embodiment
Embodiment 1
The preparation method 1 of chlorogenic acid V-type crystal prototype:
Use 200ml acetone 1g chlorogenic acid raw material to be dissolved completely under normal temperature (25 DEG C) condition as solvent, under the vacuum of 40 DEG C, the dry solvent of removing, obtains chlorogenic acid V-type crystal prototype 1, and its x-ray diffractogram of powder spectrum is consistent with Fig. 1.
The preparation method 2 of chlorogenic acid V-type crystal prototype:
Use 75ml methyl alcohol 1g chlorogenic acid raw material to be dissolved completely under normal temperature (25 DEG C) condition as solvent, under the vacuum of 40 DEG C, the dry solvent of removing, obtains chlorogenic acid V-type crystal prototype 2, and its x-ray diffractogram of powder spectrum is consistent with Fig. 1.
The preparation method 3 of chlorogenic acid V-type crystal prototype:
Use 100ml ethanol 1g chlorogenic acid raw material to be dissolved completely under normal temperature (25 DEG C) condition as solvent, under the vacuum of 50 DEG C, the dry solvent of removing, obtains chlorogenic acid V-type crystal prototype 3, and its x-ray diffractogram of powder spectrum is consistent with Fig. 1.
The preparation method 4 of chlorogenic acid V-type crystal prototype:
Use 100ml95% ethanol 1g chlorogenic acid raw material to be dissolved completely under normal temperature (25 DEG C) condition as solvent, the lower standing solid of separating out of room temperature (20 DEG C) is dry after filtration again, obtain chlorogenic acid V-type crystal prototype 4, its x-ray diffractogram of powder spectrum is consistent with Fig. 1.
The preparation method 5 of chlorogenic acid V-type crystal prototype:
Use 200ml acetone and 200ml Virahol 1g chlorogenic acid raw material to be dissolved completely under normal temperature (25 DEG C) condition as mixed solvent, the dry solvent of removing under the vacuum of 35 DEG C, obtain chlorogenic acid V-type crystal prototype 5, its x-ray diffractogram of powder spectrum is consistent with Fig. 1.
The preparation method 6 of chlorogenic acid V-type crystal prototype:
Use 200ml acetone and 600ml water 1g chlorogenic acid raw material to be dissolved completely under normal temperature (25 DEG C) condition as mixed solvent, dry after filtration again at 10 DEG C of standing solids of separating out, obtain chlorogenic acid V-type crystal prototype 6, its x-ray diffractogram of powder spectrum is consistent with Fig. 1.
The preparation method 7 of chlorogenic acid V-type crystal prototype:
Use 200ml acetone and 200ml chloroform 1g chlorogenic acid raw material to be dissolved completely under normal temperature (25 DEG C) condition as mixed solvent, the lower standing solid of separating out of room temperature (20 DEG C) is dry after filtration again, obtain chlorogenic acid V-type crystal prototype 7, its x-ray diffractogram of powder spectrum is consistent with Fig. 1.
The preparation method 8 of chlorogenic acid V-type crystal prototype:
Use 100ml95% ethanol and 50ml toluene 1g chlorogenic acid raw material to be dissolved completely under normal temperature (25 DEG C) condition as mixed solvent, drain fast removal solvent at 60 DEG C, obtain chlorogenic acid V-type crystal prototype 8, its x-ray diffractogram of powder spectrum is consistent with Fig. 1.
The preparation method 9 of chlorogenic acid V-type crystal prototype:
Use 100ml95% ethanol and 100ml chloroform 1g chlorogenic acid raw material to be dissolved completely under normal temperature (25 DEG C) condition as mixed solvent, drain fast removal solvent at 60 DEG C, obtain chlorogenic acid V-type crystal prototype 9, its x-ray diffractogram of powder spectrum is consistent with Fig. 1.
The preparation method 10 of chlorogenic acid V-type crystal prototype:
Use 75ml methyl alcohol and 10ml chloroform 1g chlorogenic acid raw material to be dissolved completely under normal temperature (25 DEG C) condition as mixed solvent, drain fast removal solvent at 40 DEG C, obtain chlorogenic acid V-type crystal prototype 10, its x-ray diffractogram of powder spectrum is consistent with Fig. 1.
The preparation method 11 of chlorogenic acid V-type crystal prototype:
Use 75ml methyl alcohol and 20ml toluene 1g chlorogenic acid raw material to be dissolved completely under normal temperature (25 DEG C) condition as mixed solvent, drain fast removal solvent at 45 DEG C, obtain chlorogenic acid V-type crystal prototype 11, its x-ray diffractogram of powder spectrum is consistent with Fig. 1.
The preparation method 12 of chlorogenic acid V-type crystal prototype:
Use 75ml methyl alcohol and 20ml water 1g chlorogenic acid raw material to be dissolved completely under normal temperature (25 DEG C) condition as mixed solvent, drain fast removal solvent at 50 DEG C, obtain chlorogenic acid V-type crystal prototype 12, its x-ray diffractogram of powder spectrum is consistent with Fig. 1.
The preparation method 13 of chlorogenic acid V-type crystal prototype:
Be controlled at 210 DEG C by temperature, by after 1g chlorogenic acid raw materials melt again through 20 DEG C of normal pressure preparation process conditions of envrionment temperature, obtain chlorogenic acid V-type crystal prototype 13, its x-ray diffractogram of powder spectrum is consistent with Fig. 1.
The preparation method 14 of chlorogenic acid V-type crystal prototype:
Be controlled at 220 DEG C by temperature, by DEG C normal pressure preparation process condition through envrionment temperature-4 again after 1g chlorogenic acid raw materials melt, obtain chlorogenic acid V-type crystal prototype 14, its x-ray diffractogram of powder spectrum is consistent with Fig. 1.
Embodiment 2
Absorption Characteristics and the Plasma Concentration feature of chlorogenic acid V-type crystal in rat body:
Laboratory animal: SD rat, male, body weight 300g.Be purchased from laboratory animal institute of the Chinese Academy of Medical Sciences.
Experimental technique: use the chlorogenic acid V-type crystal prototype 1 of embodiment 1, be mixed with 10mg/ml suspension with 4 DEG C of Wahaha Pure Waters.Rat is raised under routine raising condition, freely drinks water, and after fasting 12h, gives medicine by 100mg/kg gavage.After administration, 0.083,0.25,0.5,1,1.5,2,3,4,6 (h) time point is got the about 0.4ml of blood from eyeball posterior vein, the centrifugal 10min of 5000rpm.Get 100 μ l blood plasma, add methyl alcohol 200 μ l, vortex oscillation 2min, the centrifugal 10min of 13400rpm, gets supernatant layer 40 μ l and carries out HPLC detection.
Detecting instrument and condition: detection system is Aligent1200 highly effective liquid phase chromatographic system, chromatographic column is that (250 × 4.6mm, m), moving phase is acetonitrile: 0.05%H to 5 μ to Agilent Zorbax Eclipse XDB-C18
3pO
4damping fluid=17:83, sample size is 40 μ l, and flow velocity is 1ml/min, and detection wavelength is 328nm, and column temperature is 25 DEG C.Detected result sees the following form.
The Plasma Concentration data of chlorogenic acid V-type crystal prototype
Experimental result shows: chlorogenic acid V-type crystalline substance can be absorbed by rat, it is characterized in that can being absorbed after the administration of chlorogenic acid V-type crystalline solids medicine oral administration, can reach maximum plasma concentration and also continue to keep 3 hours platform cycles and play a role after 15 minutes.Chlorogenic acid V-type crystal as activeconstituents ensured its Absorption Characteristics in vivo, effectively bioavailability, effective blood drug concentration, stablize the lasting time and reach prevention, treatment, health-care effect and the application of making the most of the advantage.
Embodiment 3
The preparation of medicinal tablet:
The chlorogenic acid V-type crystal preparing in above-described embodiment 1 is mixed with lactose, starch, low-substituted hydroxypropyl cellulose, Microcrystalline Cellulose, add 1% sodium cellulose glycolate solution and make soft material, by the granulation of sieving of soft material, the grain that will wet is dried, sieve, add talcum powder and Magnesium Stearate to mix, compressing tablet, makes the medicinal tablet of following various dosages again.
The formula of table 2 medicinal tablet
The preparation of pharmaceutical capsule:
The chlorogenic acid V-type crystal preparing in above-described embodiment 1 is mixed with lactose, starch, Microcrystalline Cellulose, add 1% sodium cellulose glycolate solution and make soft material, by the granulation of sieving of soft material, the grain that will wet is dried, sieve, add again Magnesium Stearate to mix, incapsulate the pharmaceutical capsule that makes following various dosages; Or directly chlorogenic acid V-type crystal is mixed with all auxiliary materials shown in table 3, after sieving, incapsulate the pharmaceutical capsule that makes following various dosages.
The formula of table 3 pharmaceutical capsule
Embodiment 4
The preparation of troche of health products:
The chlorogenic acid V-type crystal preparing in above-described embodiment 1 is mixed with lactose, starch, low-substituted hydroxypropyl cellulose, Microcrystalline Cellulose, add 1% sodium cellulose glycolate solution and make soft material, by the granulation of sieving of soft material, the grain that will wet is dried, sieve, add talcum powder and Magnesium Stearate to mix, compressing tablet, makes the troche of health products of following various dosages again.
The formula of table 4 troche of health products
The preparation of health product capsule:
The chlorogenic acid V-type crystal preparing in above-described embodiment 1 is mixed with lactose, starch, Microcrystalline Cellulose, add 1% sodium cellulose glycolate solution and make soft material, by the granulation of sieving of soft material, the grain that will wet is dried, sieve, add again Magnesium Stearate to mix, incapsulate the health product capsule that makes following various dosages; Or directly chlorogenic acid V-type crystal is mixed with all auxiliary materials shown in table 5, after sieving, incapsulate the health product capsule that makes following various dosages.
The formula of table 5 health product capsule
Need the problem of explanation: pharmaceutical composition or the healthcare products of the chlorogenic acid V-type crystal the present invention relates to are permitted multifactorial impact on the dosage of effective constituent.These factors for example have: for preventing different with the purposes for the treatment of and causing the difference of dosage every day; Ill character is different from ill severity and cause the different of dosage every day; The difference of Gender, age, body surface area; Route of administration, administration number of times, therapeutic purpose are different and cause the difference of dosage every day.
Suitable dose scope every day of chlorogenic acid V-type crystal of the present invention is 0.01-300mg/kg body weight, is preferably 10-100mg/kg body weight.When use, should formulate different dosages from treatment different situations demand according to actual prevention, and can be divided into repeatedly or single administration mode completes.
Claims (12)
1. a V-type crystal for chlorogenic acid, is characterized in that, when using powder X-ray diffractometry to adopt CuK
αwhen radiation experiments condition analysis, the peak position of height %=100% is in 2 θ=17.7 ± 0.2 ° or d=
place, and have 1 disperse diffraction peak.
2. the V-type crystal of chlorogenic acid according to claim 1, it is characterized in that when using when Infrared spectroscopy, described crystal 3388,2963,2627,1693,1632,1602,1522,1445,1362,1282,1182,1162,1117,1080,1040,977,914,881,853,813,783,734,714,657,603,571,553,530,509,448,427cm
-1place has diffuse reflectance infrared spectroscopy peak, and the permissible variation at its mid-infrared spectral behavior peak is ± 2cm
-1.
3. the V-type crystal of chlorogenic acid according to claim 1, while it is characterized in that using dsc to analyze, is in the DSC collection of illustrative plates of 10 DEG C of per minutes at temperature rise rate, locates to have 1 endotherm(ic)peak at 212 DEG C ± 3 DEG C.
4. a mixing crystal-form substances for chlorogenic acid, is characterized in that, the chlorogenic acid V-type crystal described in the claim 1-3 any one that contains arbitrary proportion.
5. the preparation method of the V-type crystal of the chlorogenic acid described in claim 1-3 any one, it is characterized in that using acetone, methyl alcohol or ethanol chlorogenic acid raw material to be dissolved completely under 15 DEG C～80 DEG C temperature condition as single solvent, and prepare chlorogenic acid V-type crystal through 10 DEG C～80 DEG C of envrionment temperatures, ambient moisture 10%～75%, normal pressure or vacuum pressure condition.
6. the preparation method of the V-type crystal of the chlorogenic acid described in claim 1-3 any one, it is characterized in that, after using any two or more in methyl alcohol, ethanol, Virahol, chloroform, acetone, benzene, toluene or water to mix, at 15 DEG C～80 DEG C temperature, chlorogenic acid raw material is dissolved completely, and recrystallization under 4 DEG C～80 DEG C of envrionment temperatures, ambient moisture 10%～75%, normal pressure or vacuum pressure condition prepares chlorogenic acid V-type crystal.
7. the preparation method of the V-type crystal of the chlorogenic acid described in claim 1-3 any one, is characterized in that, adopts scorification to prepare chlorogenic acid V-type crystal; Described scorification is that temperature more than 210 DEG C is by chlorogenic acid raw materials melt, then through-10 DEG C～50 DEG C cooling V-type crystal that prepare of envrionment temperature.
8. pharmaceutical composition or healthcare products, is characterized in that, V-type crystal and the pharmaceutically acceptable carrier of the chlorogenic acid described in the claim 1-3 any one that contains effective dose.
9. pharmaceutical composition or healthcare products, is characterized in that, the mixing crystal-form substances of the chlorogenic acid claimed in claim 4 that contains effective dose and pharmaceutically acceptable carrier.
10. pharmaceutical composition or healthcare products according to claim 8 or claim 9, the every daily dosage that it is characterized in that the V-type crystal of described chlorogenic acid is 2～1000mg, preferably 10～800mg.
11. pharmaceutical composition or healthcare products according to claim 8 or claim 9, is characterized in that described pharmaceutical composition or healthcare products are tablet, hard capsule, pill, powder injection, granule, sustained release preparation or controlled release preparation.
The V-type crystal of the chlorogenic acid described in 12. claim 1-3 any one is anti-oxidant in preparation, remove free radical, improve central excitation, expanding cardiovascular, hepatic cholagogic, purposes in antitumor, anti AIDS virus, antisepsis and anti-inflammation or antianaphylactic pharmaceutical composition or healthcare products.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101691330A (en) * | 2009-09-28 | 2010-04-07 | 中南大学 | Separation and purification methods of highly purified antiviral active components in artichoke |
| CN102476997A (en) * | 2010-11-23 | 2012-05-30 | 陕西理工学院 | Method for preparing chlorogenic acid by freezing, concentrating and crystallizing |
| CN102786417A (en) * | 2011-05-18 | 2012-11-21 | 中国医学科学院药物研究所 | Chlorogenic acid crystal III characterization and preparation methods, and applications of chlorogenic acid crystal III in medicines and healthcare products |
| CN103012518A (en) * | 2012-12-14 | 2013-04-03 | 湘西自治州奥瑞克医药化工有限责任公司 | Production process for simultaneously extracting asperuloside and chlorogenic acid from folium cortex eucommiae |
| CN103183616A (en) * | 2012-12-06 | 2013-07-03 | 长沙理工大学 | Method for preparing chlorogenic acid from leaves of lonicera hypoglauca miq |
-
2014
- 2014-06-06 CN CN201410250835.2A patent/CN104016863A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101691330A (en) * | 2009-09-28 | 2010-04-07 | 中南大学 | Separation and purification methods of highly purified antiviral active components in artichoke |
| CN102476997A (en) * | 2010-11-23 | 2012-05-30 | 陕西理工学院 | Method for preparing chlorogenic acid by freezing, concentrating and crystallizing |
| CN102786417A (en) * | 2011-05-18 | 2012-11-21 | 中国医学科学院药物研究所 | Chlorogenic acid crystal III characterization and preparation methods, and applications of chlorogenic acid crystal III in medicines and healthcare products |
| CN103183616A (en) * | 2012-12-06 | 2013-07-03 | 长沙理工大学 | Method for preparing chlorogenic acid from leaves of lonicera hypoglauca miq |
| CN103012518A (en) * | 2012-12-14 | 2013-04-03 | 湘西自治州奥瑞克医药化工有限责任公司 | Production process for simultaneously extracting asperuloside and chlorogenic acid from folium cortex eucommiae |
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