CN1615838A - Composition containing dicaffeoyl quinic acid and its preparing method - Google Patents
Composition containing dicaffeoyl quinic acid and its preparing method Download PDFInfo
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- CN1615838A CN1615838A CN 200410080266 CN200410080266A CN1615838A CN 1615838 A CN1615838 A CN 1615838A CN 200410080266 CN200410080266 CN 200410080266 CN 200410080266 A CN200410080266 A CN 200410080266A CN 1615838 A CN1615838 A CN 1615838A
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- quinic acid
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Abstract
The present invention discloses composition containing dicaffeoyl quinic acid and its preparation process. The composition is suspension, gel or solution with or without dispersing medium. The composition is easy to take, acceptable, and especially suitable for long term taking and for children, aged people and people with dysphagia. The present invention also provides the preparation process of dicaffeoyl quinic acid solution.
Description
Technical field
The present invention relates to field of medicaments, particularly a kind of composition and method of making the same that contains dicaffeoyl quinic acid.
Background technology
(Dicaffeoylquinic acid DCQA), also claims dicaffeoylquinic acid to dicaffeoyl quinic acid.It is two caffeic acid esters of quinic acid, according to coffee acyl the position of substitution difference, can have 1; 5-two-O-caffeoyl guinic acid, 1,3-two-O-caffeoyl guinic acid; 1,4-two-O-caffeoyl guinic acid, 3; 5-two-O-caffeoyl guinic acid, 3,4-two-O-caffeoyl guinic acid; 4; 5-two-O-caffeoyl guinic acid, wherein 1, the report of 5-two-O-caffeoyl guinic acid is more.1, the chemistry of 5-two-O-caffeoyl guinic acid is called (1s, 1 α, 3 β, 4 α, 5 α) 1, two [[3-(3, the 4-the dihydroxy phenyl)-1-oxo-2-acrylic] oxygen] 4 of 3-, 5-dihydroxy-cyclohexane acid, molecular formula C
25H
24O
12Dicaffeoyl quinic acid is as a kind of pharmacological component, and its sphere of action is more extensive, has antiviral (CN1087608; EP1008344; US6331565; US20020111382), antioxidation (CN1136434; Sun Yanrong, Dong Junxing, etc., institute of Military Medical Science Institute periodical, 39), improve immunologic function (CN1136434), anti-liver injury (CN1476842 2002,26 (1):; Sun Yanrong, Dong Junxing, etc., institute of Military Medical Science Institute periodical, 39), antimutagenic (YoshimotoM., et al., Biosci Biotechnol Biochem 2002,26 (1):, 2002,66 (11): 2336) effect such as, at viral infection, cardiovascular disease (CN1136434; CN1381236; CN1462620; KR2002085507) etc. there is certain curative effect the aspect.Particularly for hepatitis B virus (CN1087608; EP1008344; US6331565), HIV (human immunodeficiency virus) (CN1087608; EP1008344; US6331565), coronavirus infection (CN1449751), dicaffeoyl quinic acid has the special treatment effect.Also the someone uses it for cosmetics (EP577516; US5445816).
Dicaffeoyl quinic acid can obtain (EP0299107) by separating from the plant that contains this composition, also can be obtained by chemosynthesis.The plant or the plant parts that contain dicaffeoyl quinic acid have Flos Inulae, siphonostegia chinensis, L. similis Hemsl alabastrum etc.But the method referenced patent CN1270955 and the US5401858 of chemosynthesis.
The inventor finds that this compounds has the special physicochemical properties that are different from other micromolecule organic compound in the process of research dicaffeoyl quinic acid preparation.With 1,5-two-O-caffeoyl guinic acid is an example, it is insoluble in water, be soluble in ethanol, but behind its chance water, form very sticking gel at once on the pressed powder surface, it is inner and powder can't be disperseed to have stoped hydrone to enter powder, and after making powder contact water by extraneous mechanical force, powder can produce great viscosity and make the medicine powder lumping, is difficult to disperse.This character similar some be insoluble in the polymer of water, and bring very big difficulty for the preparation research of dicaffeoyl quinic acid.The further investigation of process aspect the pharmaceutics specialty, we have prepared the oral tablet of dicaffeoyl quinic acid, can meet the general requirement of state-promulgated pharmacopoeia to oral tablet, also can satisfy clinical instructions for use substantially.
The dosage less (100mg/ sheet) of the present dicaffeoyl quinic acid oral tablet of using, sheet is heavy bigger, and the amount of at every turn taking is big (3-5 sheet), and take number of times 2-3 every day, for chronic diseases such as hepatitis B, acquired immune deficiency syndrome (AIDS), cardiovascular disease, this medicine need be taken for a long time.The mode of taking of conventional tablet or other solid preparation is to take a large amount of solid preparations (as tablet or capsule) with suitable quantity of water every day, brings some inconvenience not only for general patient, and brings very big inconvenience especially for the patient of child, old man and dysphagia.
The pharmaceutics professional and technical personnel is at long-term prescription, and patient's oral medication characteristics of child, old man and dysphagia, develop many convenient dosage forms of taking, comprise liquid, semiliquid and semisolid dosage form, and can obtain liquid, semiliquid and semisolid dosage form through adding processing such as disperse medium before use.Liquid, semiliquid and semisolid dosage form comprise solution, suspensoid, Emulsion, syrup, aromatic water, spirit, elixir, tincture, glycerin, mucilage, gel etc., and be concrete as SHUANGHUANGLIAN KOUFUYE, Atovaquone suspensoid, cough syrup, aqua methnae, aromatic ammonia spirit, pepsin elixir, Pericarpium Citri junoris tincture, mucialga of arabic gummy, acetaminophen gel.Can be before use obtain liquid, semiliquid and semisolid dosage form and comprise dry suspension, dispersible tablet, effervescent tablet etc. through adding processing such as disperse medium, also just like the solid dispersion of some type, add water and stir the powder or the granule that can become gel, concrete as chloromycetin dry suspension, aspirin dispersible tablet, vitamin C effervescent tablet.
Summary of the invention
The invention provides a kind of composition and method of making the same that contains dicaffeoyl quinic acid.Said composition has been suspension, gel or solution before oral, or adds disperse medium be dispersed into suspension, gel or be dissolved into solution before oral.The said composition taking convenience is easy to be accepted by people, is specially adapted to take for a long time the crowd of this medicine, and child, old man and swallow the crowd of comparison difficulty.
The compositions that contains dicaffeoyl quinic acid among the present invention, its dosage form can be suspensoid, solution, syrup, aromatic water, spirit, elixir, tincture, glycerin, mucilage, gel, dry suspension, dispersible tablet, effervescent tablet, serves as preferred with suspensoid, solution, gel, dry suspension, effervescent tablet wherein.
Dicaffeoyl quinic acid among the present invention; the replacement mode of coffee acyl on the quinic acid group can have many kinds; corresponding compounds comprises 1,5-two-O-caffeoyl guinic acid, 1,3-two-O-caffeoyl guinic acid, 1; 4-two-O-caffeoyl guinic acid, 3; 5-two-O-caffeoyl guinic acid, 3,4-two-O-caffeoyl guinic acid, 4,5-two-O-caffeoyl guinic acid; preferably 1,5-two-O-caffeoyl guinic acid.
The compositions that contains dicaffeoyl quinic acid among the present invention can contain buffer system, promptly adds acidity regulator in composite formula.Acidity regulator or pH regulator agent can be selected from lactic acid, citric acid, hydrochloric acid, tartaric acid, boric acid, acetic acid, phosphoric acid, sodium dihydrogen phosphate, potassium dihydrogen phosphate, sodium carbonate, sodium bicarbonate, sodium citrate, sodium acetate, sodium lactate, sodium hydrogen phosphate, dipotassium hydrogen phosphate, tartrate, sodium hydroxide, Borax, Tris, preferably lactic acid, citric acid, acetic acid, sodium dihydrogen phosphate, sodium hydrogen phosphate, sodium carbonate, sodium bicarbonate, sodium citrate.Acidity regulator exists in the solution mode in compositions, also can be present in the solid preparation by solid form.
When the compositions that contains dicaffeoyl quinic acid among the present invention exists with solution, suspension or gel form, or compositions adds in the solution that is dispersed into behind the disperse medium, suspension, the gel, their pH is not restricted, but after adding acidity regulator, their pH scope can be 1-14, preferably 2-7, more preferably 3-5.
The compositions that contains dicaffeoyl quinic acid among the present invention can contain antioxidant.Antioxidant can be selected from sodium sulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, thiourea, vitamin C, cysteine, thioglycerol, vitamin E butylated hydroxyarisol, two fourth cresols, PG, preferably sodium sulfite, vitamin C.
In order to make the compositions that contains dicaffeoyl quinic acid among the present invention be more prone to be accepted when the oral application, in compositions, can add sweeting agent by people.Sweeting agent can be selected from glucide or its sodium salt, stevioside, aspartame, cyclamate, glycyrrhizin, preferably saccharin sodium, stevioside, aspartame.Can also add aromatic in the compositions.Aromatic can be selected from various natural and artificial essence and fragrant flavoring agent, concrete as vanillin, cinnamic aldehyde, fragrant lance alcohol, eucalyptol, petitgrain oil, fennel oil, menthol, Oleum menthae, Fructus Citri Limoniae essence, cherry essence, strawberry essence, flavoring pineapple essence, Fructus Myricae rubrae essence, grape essence, chocolate essence, coffee aroma, flavoring peach essence, preferably vanillin, fennel oil, menthol, Fructus Citri Limoniae essence, grape essence, chocolate essence.Can also add coloring agent in the compositions.Coloring agent can be selected from carotene, sunset yellow, beet red, lemon yellow, chlorophyll, carmine, amaranth, erythrosine.
Contain among the present invention in the compositions of dicaffeoyl quinic acid and can add antiseptic.Antiseptic can be selected from methyl parahydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate, benzoic acid and salt thereof, sorbic acid and salt thereof.
For the dicaffeoyl quinic acid compositions that has been suspension, gel before oral, can be with reference to the conventional preparation method preparation of this professional field, preparation process generally comprises dicaffeoyl quinic acid and auxiliary materials and mixing, obtains again with after disperse medium mixes.Disperse medium can be selected from water, aqueous solution, rubber cement liquid, preferably water.Aqueous solution comprise various salt aqueous solution, micromolecule adjuvant aqueous solution and contain the aqueous solution of the organic solvent (as ethanol) that part can dissolve each other with water.
For the solution of dicaffeoyl quinic acid, need in preparation, add cosolvent.Cosolvent can be selected from ethanol, ethylene glycol, propylene glycol, glycerol, Polyethylene Glycol, acetic acid, N ', dinethylformamide, dimethyl sulfoxide, preferably ethanol, propylene glycol, glycerol, Polyethylene Glycol.
The solution of the dicaffeoyl quinic acid among the present invention, the present invention can adopt following preparation technology:
(1) dicaffeoyl quinic acid is dissolved in cosolvent;
(2) above-mentioned solution joins in water or the aqueous solution, mixing.
The course of dissolution of (1) in the above-mentioned technology can adopt stirring, heating, means such as ultrasonic to promote the dissolving of dicaffeoyl quinic acid in cosolvent.When the adition process of (2) can keep water or aqueous solution to be quick stirring in the above-mentioned technology, the dicaffeoyl quinic acid cosolvent solution is splashed into.
For before oral, adding the dicaffeoyl quinic acid compositions that aqueous dispersion becomes suspension, gel or is dissolved into solution, preparation process generally comprises dicaffeoyl quinic acid and suitable auxiliary materials and mixing is obtained, and also can obtain after suspension, gel or the solution drying with above-mentioned dicaffeoyl quinic acid.Drying process such as spray drying, fluid bed drying, lyophilization.This compositions obtains suspension, gel or solution after after facing with preceding adding disperse medium it being dispersed or dissolved.Disperse medium can be selected from water, aqueous solution, rubber cement liquid, preferably water.Aqueous solution comprise various salt aqueous solution, micromolecule adjuvant aqueous solution and contain the aqueous solution of the organic solvent (as ethanol) that part can dissolve each other with water.
The specific embodiment
Embodiment 1. dicaffeoyl quinic acid suspensoids
1,5-two-O-caffeoyl guinic acid 2.5g
Sucrose 4g
Microcrystalline Cellulose 4g
Saccharin sodium 0.1g
Citric acid 0.1g
Sodium citrate 0.2g
Vitamin C 0.2g
Sodium benzoate 0.2g
Vanillin is an amount of
Xanthan gum 1g
Water 100ml
With 1,5-two-O-caffeoyl guinic acid, sucrose, microcrystalline Cellulose are pulverized jointly, cross 80 mesh sieves, mixing.All the other compositions are water-soluble, obtain the rubber cement liquid of certain viscosity.Rubber cement liquid is slowly added in the top mixed-powder, and the limit edged grinds, and obtains the uniform dicaffeoyl quinic acid suspensoid of suspendible at last.
One of embodiment 2. dicaffeoyl quinic acid solutions
1,5-two-O-caffeoyl guinic acid 2g
Propylene glycol 20ml
Vitamin C 0.2g
Lactic acid 0.2g
Benzoic acid 0.1g
Aspartame 0.2g
Water 50ml
Get 1,5-two-O-caffeoyl guinic acid and propylene glycol, heating for dissolving slowly splashes in the aqueous solution that contains vitamin C, lactic acid, benzoic acid, aspartame that is stirring, and obtains clarifying dicaffeoyl quinic acid solution.
Two of embodiment 3. dicaffeoyl quinic acid solutions
3,5-two-O-caffeoyl guinic acid 2g
PEG400 20ml
Vitamin C 0.1g
Lactic acid 0.1g
Sorbic acid 0.05g
Aspartame 0.1g
Water 50ml
Get 3,5-two-O-caffeoyl guinic acid and PEG400, heating for dissolving slowly splashes in the aqueous solution that contains vitamin C, lactic acid, sorbic acid, aspartame that is stirring, and obtains clarifying dicaffeoyl quinic acid solution.
Embodiment 4. dicaffeoyl quinic acid gels
4,5-two-O-caffeoyl guinic acid 2.5g
Sucrose 6g
Sodium alginate 10g
Calcium lactate 5g
Vitamin C 0.5g
Stevioside 0.2g
Fructus Citri Limoniae essence is an amount of
Lemon yellow is an amount of
Ethylparaben 0.1g
Propyl p-hydroxybenzoate 0.1g
Water 100ml
Get 4,5-two-O-caffeoyl guinic acid, sucrose, sodium alginate, ethylparaben, propyl p-hydroxybenzoate are pulverized jointly, cross 80 mesh sieves, and mixing adds suitable quantity of water, grinds and stirs, and obtains viscous liquid.Get all the other compositions and add entry and obtain solution, join gradually in the above-mentioned viscous liquid, obtain the dicaffeoyl quinic acid gel.
Embodiment 5. dicaffeoyl quinic acid dry suspension
1,5-two-O-caffeoyl guinic acid 2.5g
Microcrystalline Cellulose 4g
Citric acid 0.1g
Sodium citrate 0.2g
Sodium sulfite 0.2g
Low-substituted hydroxypropyl cellulose 1g
Saccharin sodium 0.1g
Vanillin is an amount of
Xanthan gum 1g
All the components is pulverized jointly in will writing out a prescription, and crosses 80 mesh sieves, and mixing is used 95% alcohol granulation, crosses 18 mesh sieves, and room temperature is dried, and granulate obtains the dicaffeoyl quinic acid dry suspension.
In above-mentioned dicaffeoyl quinic acid dry suspension, add about 60 ℃ 100ml water, obtain uniform suspension.
Embodiment 6. dicaffeoyl quinic acid effervescent tablets
1,5-two-O-caffeoyl guinic acid 2.5g
Lactose 3g
Citric acid 0.8g
Saccharin sodium 0.1g
Vitamin C 0.2g
Vanillin is an amount of
Sodium bicarbonate 0.9g
Sodium carbonate 0.2g
Magnesium stearate 0.05g
Other composition except that magnesium stearate in the prescription is pulverized jointly, crossed 80 mesh sieves, mixing is granulated with dehydrated alcohol, crosses 18 mesh sieves, and about 50 ℃ of oven dry add the magnesium stearate mixing, cross 18 mesh sieves, with the flat stamping of 12mm, obtain the dicaffeoyl quinic acid effervescent tablet.
After this tablet added water, slowly effervescent became basic settled solution in 3 minutes.
Claims (10)
1. a compositions that contains dicaffeoyl quinic acid is characterized in that said composition has been suspension, gel or solution before oral, or adds disperse medium be dispersed into suspension, gel or be dissolved into solution before oral.
2. dicaffeoyl quinic acid as claimed in claim 1 is 1,5-two-O-caffeoyl guinic acid.
3. the compositions that contains dicaffeoyl quinic acid as claimed in claim 1, dosage form comprises suspensoid, solution, gel, dry suspension, effervescent tablet.
4. disperse medium as claimed in claim 1 is a water.
5. the compositions that contains dicaffeoyl quinic acid as claimed in claim 1 contains acidity regulator.
6. the compositions that contains dicaffeoyl quinic acid as claimed in claim 1, under liquid condition or the pH value under the liquid condition after adding disperse medium in the 2-7 scope.
7. the compositions that contains dicaffeoyl quinic acid as claimed in claim 1 contains antioxidant.
8. the compositions that contains dicaffeoyl quinic acid as claimed in claim 1 when existing with the solution form, contains cosolvent.
9. cosolvent as claimed in claim 8 is selected from ethanol, propylene glycol, glycerol, Polyethylene Glycol.
10. solution as claimed in claim 3, the step of its preparation method is:
(1) dicaffeoyl quinic acid is dissolved in cosolvent and becomes solution;
(2) above-mentioned solution joins in water or the aqueous solution, mixing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100802668A CN100353938C (en) | 2004-09-29 | 2004-09-29 | Composition containing dicaffeoyl quinic acid and its preparing method |
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2004100802668A CN100353938C (en) | 2004-09-29 | 2004-09-29 | Composition containing dicaffeoyl quinic acid and its preparing method |
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| CN1615838A true CN1615838A (en) | 2005-05-18 |
| CN100353938C CN100353938C (en) | 2007-12-12 |
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| CNB2004100802668A Expired - Fee Related CN100353938C (en) | 2004-09-29 | 2004-09-29 | Composition containing dicaffeoyl quinic acid and its preparing method |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113727614A (en) * | 2019-04-06 | 2021-11-30 | 嘉吉公司 | Sensory modifier |
| CN113784626A (en) * | 2019-04-06 | 2021-12-10 | 嘉吉公司 | Gasified solutions with improved organoleptic properties |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1087608C (en) * | 1996-08-29 | 2002-07-17 | 中国人民解放军军事医学科学院放射医学研究所 | Use of dicafeoyl quininic acid in treatment of hepatitis B and diseases associated with retrovirus and cafeoyl quininic acid derivs. |
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2004
- 2004-09-29 CN CNB2004100802668A patent/CN100353938C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113727614A (en) * | 2019-04-06 | 2021-11-30 | 嘉吉公司 | Sensory modifier |
| CN113784626A (en) * | 2019-04-06 | 2021-12-10 | 嘉吉公司 | Gasified solutions with improved organoleptic properties |
| US11918014B2 (en) | 2019-04-06 | 2024-03-05 | Cargill, Incorporated | Sensory modifiers |
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| Publication number | Publication date |
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| CN100353938C (en) | 2007-12-12 |
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Granted publication date: 20071212 Termination date: 20120929 |