CN100444847C - Micronize diosmin and hesperidine composition suppository - Google Patents
Micronize diosmin and hesperidine composition suppository Download PDFInfo
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- CN100444847C CN100444847C CNB2006100006751A CN200610000675A CN100444847C CN 100444847 C CN100444847 C CN 100444847C CN B2006100006751 A CNB2006100006751 A CN B2006100006751A CN 200610000675 A CN200610000675 A CN 200610000675A CN 100444847 C CN100444847 C CN 100444847C
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- suppository
- diosmin
- hesperidin
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Abstract
The present invention relates to a composition suppository of micronized diosmin and hesperidine, which is clinically used as a medicine for treating hemorrhoid, phlebitis and varicosity. The suppository comprises diosmin, hesperidin, suppository bases and additives, wherein the weight ratio of the diosmin to the hesperidin is from 5: 1 to 15: 1, the powder fineness of at least 80 % of diosmin and hesperidin is smaller than 20 mu m. The suppository has the advantages of conspicuous curative effect, rapid effect, good absorptivity and small stimulation.
Description
Invention field
The present invention relates to medical technical field, exactly the present invention relates to a kind of micronize diosmin and hesperidine composition suppository, it is clinically as hemorrhoid, anti-phlebitis and varicosis agent.
Background of invention
Hemorrhoid, phlebitis, varicosis all are a kind of common frequently-occurring diseases, be unusual by hemorheology, microcirculation is bad etc., and multiple complicated factor causes.At present this treatment of diseases method is divided into operative treatment and Drug therapy, though operative treatment is comparatively thorough, the patient suffering, and be difficult to avoid its place's recurrence, also may stay certain sequela such as anal stenosis etc. simultaneously.Therefore, the general Drug therapys that adopt of patient more, the dust head is medicine for external use such as HUAZHI SHUAN, ZHICHUANG GAO etc., it act as detumescence, hemostasis, antiinflammatory.Disclose a kind of ZHICHUAN SHUAN in Chinese patent application CN1088824A, by the suppository that kinds of traditional Chinese medicines is made, have characteristics easy to use, but curative effect has been not remarkable, the effect that it plays relief of symptoms, eases the pain does not reach the effect of radical cure.About phlebitis, cirsoid treatment, the much more existing family of China's the eighties produces troxerutin drugs, takes inconvenient and defective such as side effect is arranged but also exist, and can not effectively treat at hemorrhoid.
Scientist finds that in research process flavone compound is the natural nutrient of newfound needed by human, when lacking flavonoid in the human body, causes diseases such as sclerosis of blood vessels, fragility enhancing easily.Therefore adopt flavone compound to come the treatment of vascular disease, prevent thrombosis, microcirculation improvement has broad prospects.Take charge of bright and hesperidin all is a kind of flavone compound difficult to understandly, and they are the natural organic-compounds that extensively are present in the plant, are many medium-height grass the effective elements of the medicines, and the diosmin structural formula is:
Molecular formula: C
28H
32O
15, molecular weight: 608.6, chemical name: 7-[[6-O-(6--＜-L-mannopyranose base)-β-D-glucopyranosyl] the oxygen base]-5-hydroxyl-2-(3-hydroxyl-4-methoxyl group)-4H-1-.alpha.-5:6-benzopyran-4-ketone;
The structural formula of hesperidin is:
Molecular formula: C
28H
34O
15, molecular weight: 610.6, chemical name: (2S)-and 7-[[6-O-(6-deoxidation-L-mannopyranose base)-β-D-glucopyranosyl] the oxygen base]-5-hydroxyl-2-(3-hydroxyl-4-methoxyl group)-2,3-dihydro-4H-1-.alpha.-5:6-benzopyran-4-ketone.They have blood pressure lowering, blood fat reducing, enhance immunity, reduction vascular fragility, prevent thrombosis, improve effects such as blood circulation.
Diosmin and hesperidin can act on three blood vessels all sidedly and feed back system.For Venous system, act on the time that wall of vein causes contraction by prolonging norepinephrine, thereby strengthen venous tension force.It has special affinity and does not influence Arterial system vein.The second, for microcirculqtory system, can obviously reduce the adhesion of leukocyte and vascular endothelial cell, divide a word with a hyphen at the end of a line, disintegrate discharges the inflammatory material, as histamine, Kallidin I, complement, leukotriene, prostaglandin, too much free radical etc., thus reduce the permeability of blood capillary and strengthen its resistance, also have the reduction blood viscosity, strengthen the function of red cell velocity, thereby reduce microcirculation stasis situation.The 3rd, for lymphsystem, increase lymphatic drainage speed and lymphatic vessel contraction, thereby accelerate the backflow of interstitial fluid, improve lymphatic return, alleviate edema.
At present existing diosmin and the listing of hesperidin mixture tablet, clinically as hemorrhoid, anti-phlebitis and varicosis agent, but there is first pass effect in it, cause a large amount of flavone losses, bioavailability is low, causes the dosage taken big, takes often.Make troubles for busy patient's medication, often can not take on time, cause blood drug level not maintain in the therapeutic domain.And the dosage of taking is big, causes the raising of cost, also brings the certain economic burden to the patient.
Therefore diosmin and hesperidin mixture are prepared into quick-acting, stablize and preparation that bioavailability is high is a difficult problem of this area always.
Summary of the invention
The objective of the invention is to overcome the defective of existing diosmin and the existence of hesperidin mixture oral medicine dosage form; by with diosmin and hesperidin micronize, adopt specific pharmaceutic adjuvant and proportioning that micronize diosmin and hesperidine composition are made suppository; solved the problems referred to above effectively, thereby a kind of evident in efficacy, rapid-action, good, bland micronize diosmin of absorbability and hesperidine composition suppository are provided.Specifically; by with after a certain proportion of diosmin and the processing of hesperidin micronize, add a certain proportion of suppository base and additives, in conjunction with the characteristics of suppository; make between each composition and produced synergy, cause this product easily to absorb, stimulate little and characteristics such as bioavailability height.
One object of the present invention just provides a kind of micronize diosmin and hesperidine composition suppository.
Another object of the present invention provides a kind of method for preparing described micronize diosmin and hesperidine composition suppository.
The present invention realizes by following technical scheme:
A kind of micronize diosmin and hesperidine composition suppository, every piece of suppository comprises:
Diosmin 2mg-4.8g
Hesperidin 0.5mg-1g
Suppository base 10mg-5g
Additives 0-3g,
Wherein the weight ratio of diosmin and hesperidin is 5: 1-15: 1.
Preferably, a kind of micronize diosmin of the present invention and hesperidine composition suppository, every piece of suppository comprises:
Diosmin 5mg-4.5g
Hesperidin 0.8mg-0.8g
Suppository base 20mg-3g
Additives 0-1g
Wherein the weight ratio of diosmin and hesperidin is 6: 1-12: 1.
Diosmin of the present invention and hesperidine composition suppository are that diosmin, hesperidin and the suitable substrate of micronize purification is made the solid preparation for cavity/canal drug administration.Suppository has suitable hardness and toughness, nonirritant, after introducing tract, energy fusion under the body temperature condition, softening or dissolving, and easily mix with juice, discharge medicine gradually and produce local action or general action, its advantage is: during as hemorrhoid, can directly act on diseased region, directly onset; During as anti-phlebitis and varicosis agent, medicine absorbs from rectum, is not subjected to the destruction of gastrointestinal pH or enzyme, the destruction that is subjected to the liver first-pass effect in the time of can avoiding oral, can also reduce toxicity and the side effect of medicine, and the action time of suppository is longer than general oral tablet to liver.
Because diosmin and hesperidin are insoluble in water, therefore adopt micronization technology that its mean diameter is reduced to about 0.1-10 μ m among the present invention, preferred 0.1-2.5 μ m, the fineness of powder of diosmin and hesperidin are at least 80% less than 20 μ m, and preferably at least 90% less than 2.5 μ m.Owing to reduced grain diameter, make the contact area of medicine and intestinal mucosa increase 20 times nearly, absorbability increases by 4 times than not micronized diosmin and hesperidin, medicine is easier to be absorbed by the body, shorten soak time, improve absorbtivity, improve bioavailability.
Diosmin of the present invention and hesperidine composition suppository contain micronize diosmin and hesperidin 10mg-5g altogether, preferred 100mg-1g, more preferably 500mg in every piece of suppository.The part by weight of diosmin and hesperidin is generally 5 among the present invention: 1-15: 1, preferred 6: 1-12: 1, most preferably 8: 1-10: 1.
The suppository base that adopts in micronize diosmin of the present invention and the hesperidine composition suppository comprises greasing base and water-soluble base, and greasing base comprises one or more any mixture in cocoa butter, the semi-synthetic fatty acid glyceride etc.; Water-soluble base comprises one or more any mixture in glycerin gelatine, polyethylene glycols, polyoxyethylene monostearate class, the poloxamer etc., and in every piece of suppository, the consumption of suppository base is 10mg-5g, preferred 20mg-3g.The present invention has been owing to adopted a certain proportion of substrate and micronize diosmin and hesperidin makes up, make micronize purification diosmin of the present invention and hesperidine composition suppository good moldability, promoted absorption by human body and improved bioavailability.
The additives that adopt in micronize diosmin of the present invention and the hesperidine composition suppository comprise one or more any mixture in sclerosing agent, thickening agent, absorption enhancer, antioxidant, the antiseptic.Sclerosing agent comprises one or more any mixture in white beeswax, spermol, stearic acid, the Brazil wax; Thickening agent comprises one or more any mixture in castor oil hydrogenated, glyceryl monostearate, the aluminium stearate; Absorption enhancer comprises one or more any mixing in surfactant, fatty acid, aliphatic alcohol, fatty esters, carbamide, sodium salicylate, sodium benzoate, sodium carboxymethyl cellulose, the cyclodextrin derivant; Antioxidant comprises one or more any mixture of butylhydroxy anisole (BHA), Butylated Hydroxytoluene (BHT), epicatechol gallate apoplexy due to endogenous wind.Antiseptic comprises one or more any mixing in oxybenzene Arrcostab, benzoic acid and salt, sorbic acid and salt thereof, mercury compound class, the quaternary ammonium compound, and the consumption of additives in every piece of suppository is generally 0-3g, preferred 0-1g.
Micronize diosmin among the present invention and hesperidine composition suppository can also contain emulsifying agent, coloring agent etc.
Micronize diosmin of the present invention and hesperidine composition suppository, every piece of suppository weight is generally 0.5-5g, preferred 1-4g, more preferably 1.5-3g, it is the rectally suppository formulation.
The present invention also provides a kind of method for preparing described micronize diosmin and hesperidine composition suppository, the steps include:
A. respectively diosmin and hesperidin are pulverized under high velocity air, mixed in proportion; Or diosmin and hesperidin mixed in proportion, under high velocity air, pulverize, mixed-powder;
B. with the suppository base heat fused, add the mixed-powder and the additives that obtain in the b step, mix homogeneously injects the bolt mould, and condensation promptly gets suppository of the present invention.
The present invention makes composition suppository with micronize diosmin and hesperidin, and when the treatment hemorrhoid, medicine directly acts on disease sites; absorb rapidly, evident in efficacy, if add suitable adjuvant; realize vasoconstrictive, hemostasis, pain relieving, effect such as antipruritic more help treatment of hemorrhoid.And under the less condition of using dosage, just can reach the effect of treatment, and long action time, the medication number of times obviously reduces, and can not occur because forget the blood drug level big ups and downs that medication occurs.
As anti-phlebitis and varicosis agent the time, also, improved bioavailability, and under the prerequisite that guarantees therapeutic effect, obviously reduced the dosage amount because the absorption of suppository does not have first pass effect, reduced administration number of times, prolonged action time.
Said preparation has been avoided first pass effect, improved bioavailability, under the prerequisite that guarantees therapeutic effect, obviously reduced dosage, reduced administration number of times, to patient's medication on time, blood drug level is maintained main meaning in the therapeutic domain, and reduced dosage, and reduced cost of material, also alleviated patient's financial burden.Said preparation more helps treating hemorrhoid, anti-phlebitis and varicosis.
The specific embodiment
The following example is in order further to describe the present invention for example, rather than limits the present invention by any way.
1 one kinds of micronize diosmins of embodiment and hesperidin suppository
Diosmin 45g
With hesperidin 5g
PEG 4000 80g
PEG 6000 60g
Under high gas flow; with diosmin and hesperidin micronization; make the powder that mean diameter is about 5 μ m; with PEG4000 and PEG6000 heating and melting, mix homogeneously adds micronized diosmin and hesperidin mixture; with adding with stirring; impouring scribbles in the bolt mould of lubricant, and 100 pieces of suppositorys are promptly made in condensation.
2 one kinds of micronize diosmins of embodiment and hesperidin suppository
Diosmin 42g
Hesperidin 8g
Sodium benzoate 10mg
Semi-synthetic fatty acid glyceride 150g
Under high gas flow; with diosmin and hesperidin micronization; make the powder that mean diameter is about 2.5 μ m; with micronize diosmin and hesperidin and sodium benzoate mix homogeneously, get mixed-powder, with semi-synthetic fatty acid glyceride; in water-bath, melt; mixed-powder is added in the molten matrix, stir, make into uniform suspension.Inject the bolt mould, scrape off unnecessary material after the cooling, 100 pieces of suppositorys are promptly made in the demoulding.
The effect of micronize diosmin of the present invention and hesperidine composition suppository below is described by experiment:
The pharmacokinetic characteristics of micronize diosmin of the present invention and hesperidine composition suppository and commercially available diosmin tablet and comparison.
With micronize diosmin and hesperidine composition suppository in the embodiment of the invention 1 for being subjected to test preparation; commercially available diosmin tablet is with reference to preparation; adopt the binary cycle cross matching; give 10 domesticated dogs (average weight 12.95kg) single dose (every day diosmin 450mg; hesperidin 50mg) administration; regularly blood sampling is measured blood drug level with the HPLC method after treatment.The pharmacokinetic parameters that obtains after two kinds of preparation matches is as follows:
| Commercially available diosmin tablet | The embodiment of the invention 1 micronize diosmin and hesperidine composition suppository | |
| Cmax(mg/L) | 5.125 | 8.712 |
| Tmax(h) | 1.15 | 1.02 |
| t 1/2(h) | 10.8 | 11.1 |
| AUC(mg·h/L) | 93.51 | 148.43 |
The relative bioavailability of micronize diosmin of the present invention and hesperidine composition suppository is 158.73%.The result shows that micronize diosmin of the present invention and hesperidine composition suppository are rapid-action, and the maximum plasma concentration height has improved bioavailability.
Claims (8)
1. micronize diosmin and hesperidine composition suppository is characterized in that every piece of suppository comprises:
Diosmin 2mg-4.8g
Hesperidin 0.5mg-1g
Suppository base 10mg-5g
Additives 0-3g,
Wherein suppository base is selected from greasing base and water-soluble base, and described greasing base is selected from one or more any mixture in cocoa butter, the semi-synthetic fatty acid glyceride; Described water-soluble base is selected from one or more any mixture in glycerol, gelatin, polyethylene glycols, polyoxyethylene monostearate class, the poloxamer,
Wherein the mean diameter of diosmin and hesperidin is 0.1-2.5 μ m, and the fineness of powder of at least 90% diosmin and hesperidin is less than 2.5 μ m.
2. suppository according to claim 1, its every piece suppository comprises:
Diosmin 5mg-4.5g
Hesperidin 0.8mg-0.8g
Suppository base 20mg-3g
Additives 0-1g.
3. suppository according to claim 1, wherein the weight ratio of diosmin and hesperidin is 5: 1-15: 1.
4. suppository according to claim 2, wherein the weight ratio of diosmin and hesperidin is 6: 1-12: 1.
5. suppository according to claim 4, wherein the weight ratio of diosmin and hesperidin is 8: 1-10: 1.
6. suppository according to claim 5, wherein additives comprise one or more any mixture in sclerosing agent, thickening agent, absorption enhancer, antioxidant, the antiseptic.
7. suppository according to claim 6, wherein every piece of suppository weight is 0.5-5g.
8. preparation is according to the method for the described suppository of claim 1-7, and it may further comprise the steps:
A. respectively diosmin and hesperidin are pulverized under high velocity air, mixed in proportion; Or diosmin and hesperidin mixed in proportion, under high velocity air, pulverize, mixed-powder;
B. with the suppository base heat fused, add the mixed-powder and the additives that obtain in the b step, mix homogeneously injects the bolt mould, and condensation promptly gets suppository of the present invention.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CNB2006100006751A CN100444847C (en) | 2006-01-11 | 2006-01-11 | Micronize diosmin and hesperidine composition suppository |
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| CNB2006100006751A CN100444847C (en) | 2006-01-11 | 2006-01-11 | Micronize diosmin and hesperidine composition suppository |
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| CN100444847C true CN100444847C (en) | 2008-12-24 |
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Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MD3987C2 (en) * | 2009-09-03 | 2010-07-31 | Георге АНГЕЛИЧ | Use of Diosmine for the treatment of advancing hepatic cirrhosis associated with cardiac insufficiency |
| MD3986C2 (en) * | 2009-09-23 | 2010-07-31 | Георге АНГЕЛИЧ | Use of Diosmine for the treatment of portal gastropathies in the hepatic cirrhosis |
| CN101711768B (en) * | 2009-12-18 | 2012-05-30 | 杨义靖 | Application of diosmin in manufacturing medicaments |
| MD4232C1 (en) * | 2012-11-08 | 2014-01-31 | Георге АНГЕЛИЧ | Medicament based on troxerutin and carbazochrome for the treatment of progressive hepatic cirrhosis associated with heart failure |
| MD4231C1 (en) * | 2012-11-08 | 2014-01-31 | Георге АНГЕЛИЧ | Medicament based on troxerutin and carbazochrome for the treatment of portal gastropathies in hepatic cirrhosis |
| FR2999934B1 (en) * | 2012-12-21 | 2015-02-20 | Servier Lab | PHARMACEUTICAL COMPOSITION IN THE FORM OF AN ORAL SUSPENSION COMPRISING A FLAVONOIC FRACTION AND XANTHAN GUM |
| CN103156924A (en) * | 2013-04-01 | 2013-06-19 | 金华牧之家动物药业有限公司 | Chinese medicinal suppository for treating mammal endometritis and preparation method thereof |
| MX354614B (en) * | 2013-08-09 | 2018-03-08 | Centro De Investig Y De Estudios Avanzados Del I P N | Pharmaceutical composition combining diosmin and hesperidin and its use in neuropathic pain. |
| RU2545994C1 (en) * | 2013-10-30 | 2015-04-10 | Общество с ограниченной ответственностью "Гемодан" | Suppositories for treating hemorrhoid, proctitis and other proctologic inflammations |
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| CN1310610A (en) * | 1998-07-20 | 2001-08-29 | L·拉峰试验公司 | Pharmaceutical composition in particular for preventing and treating mucositis induced by radiotherapy or chemotherapy |
| CN1528283A (en) * | 2003-10-16 | 2004-09-15 | 晏四平 | Non-injection pharmaceutical product containing novel houttuynine sodium bisulfite |
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