CN1559503A - Mango couth suppressing capsule and method of preparatuion long effect capsule - Google Patents

Abstract

A medicine in the form of capsules for treating cough with durable effect is prepared through extracting active components from fresh mango fruit, proportional mixing with sodium houttuyfonate and chlorpheniramine, granulating and loading in capsules.

Description

The preparation method of MANGGUO ZHIKE JIAONANG and spansule

Technical field

The present invention relates to a kind of Chinese medicine preparation, particularly have the preparation method of the Fructus Mangifera Indicae cough-relieving spansule of slow releasing function.

Background technology

The dosage form of Chinese patent medicine has multiple dosage forms such as unguentum, powder, pill, syrup, tablet, capsule, injection, granule through years development.These dosage forms respectively have superiority, for the space has been opened up in the development of Chinese patent medicine.

Tablet is common Chinese patent medicine dosage form, and it has following advantage: 1. the dissolution and the bioavailability of tablet are good than pill usually: 2. dosage is accurate, and the medicine content difference is less in the tablet; 3. steady quality, tablet is a drying solid, and some easy oxidation deterioration and deliquescent medicine can borrow coating be protected, light, air, moisture etc. are less to its influence; 4. take, carry, transportation etc. is more convenient; 5. mechanization production, output is big, cost is low, sanitary standard reaches easily.

But tablet also has many shortcomings: 1. need to add some excipient in the tablet, and through compression forming, dissolution is slow than powder and capsule, influences its bioavailability sometimes; 2. child and stupor person are difficult for swallowing; 3. the tablet contain that contains volatile component in content descend.

Capsule then has following characteristics

(1) bright and clean, attractive in appearance, bitterness and the stink that can cover the medicine discomfort of outward appearance is convenient to take, and makes hard capsule as Herba Andrographis etc., swallows easily.

(2) bioavailability of medicament height, supplementary product consumption is few.Compare with tablet, pill, can not add binding agent and pressure during preparation, so disintegrate disperses fast, good absorbing in gastrointestinal tract.The medicine of general clothes back disintegratable release in 3～10 minutes, fast than pill and tablet produce effects.For example indometacin capsule and tablet are distinguished once oral 100mg, and behind the 6 example clothes capsules, the concentration that peaks in the average 1.5 hours blood is 6mg/ml; Behind the 6 example clothes tablets, on average just peak, and have only 3.5mg/ml in addition at 2.5 hours blood levels.(vegetarian Teng Tailang: pharmaceutics P90-1977).And for example tegafur capsule and tablet in Sanguis Leporis seu oryctolagi concentration ratio, area under a curve is respectively 42.15 and 29.80mg/ml during medicine, the relative bioavailability of tablet is 70.7% (Lu Minglian etc.: pharmacy circular 16 (9) of capsule; 57; 1981).Carried out the contrast experiment about the tablet of Chinese patent medicine aspect and the more also someone of capsule aspect.With the contrast that Radix Ilicis Pubescentis sheet and capsule carry out release and rise burst size, the result shows 30 minutes burst size of tablet is close with 2 minutes burst size of capsule, 50 minutes burst size of capsule has been tablet 2 times.

(3) improve medicine stability.To photosensitive or meet damp and hot unsettled medicine, in the opaque capsule of can packing into, the protection medicine is not subjected to the influence of dampness, airborne oxygen, light, thereby improves its stability.

From above analysis, change suitable Chinese patent medicine tablet into capsule, can improve the Bioavailability of Human Body of Chinese patent medicine, make the pharmacological action of Chinese patent medicine more rapid, improve the treatment timeliness of Chinese patent medicine, and can reduce the taking dose of Chinese patent medicine.

But also there is weak point in the conventional capsule agent, if any the medicine disintegrate discharge and not need too soon, particularly some analgesic or influence the medicine of gastrointestinal function need certain hour to come slow release, just can play due effect.So people have developed some in recent years and have regularly located the release medicine, pass through proper method, delay medicine release, absorption, distribution, metabolism and discharge process in vivo, to reach a class preparation of prolong drug effect, concrete grammar is that medicine is made granule earlier, use the material coating of different rate of release then,, can reach the purpose of prolongation of effect in the capsulae vacuus of packing in desired ratio mixing.As ibuprofen, aspirin, paracetamol etc. all has slow releasing preparation, and document is introduced amfetamine sulfate capsule (long-acting) principal agent is divided into quarter.A quick-acting parts, three parts become 3,6,9 hours slow-release pills with the blocker coating respectively, and four kinds of pillers are distinguished with different color and lusters, and the capsulae vacuus of packing into behind the mix homogeneously can reach peak concentration in the blood in interior 30 minutes, and lasting curative effect can reach 11 hours.If need in intestinal produce effects, can be made into the enteric solubility capsule.Compare with general preparation, slow releasing preparation has 3 advantages: 1, taking convenience.General preparation often needs administration for several times on the one, and slow releasing preparation is usually only with administration every day 1-2 time.2, the general preparation effect of slow release medicine low, avoided general preparation frequent drug administration after, because of blood drug level excessive the fluctuated of effective blood drug concentration that occur that rise and fall.3, the general preparation of toxic and side effects is little.Good fat-soluble, powerful blood-brain barrier permeability.Blood medicine peak, paddy fluctuation of concentration are little, and duration of efficacy is long, make that curative effect strengthens, toxicity reduces.

MANGGUO ZHIKE PIAN is the product that suitable curative effect is arranged, and its preparation method is with the Folium mangiferae water extraction, adds Sodium Houttuyfonate, chlorphenamine and additive of tablet again, the pelletizing press sheet coating obtains behind the mixing, have dispersing lung-QI and dissipating phlegm, the effect of relieving cough and asthma is mainly used in diseases such as cough, asthma, excessive phlegm.The mechanism of action about MANGGUO ZHIKE PIAN, following report is arranged in the research article " MANGGUO ZHIKE PIAN pharmacodynamic study (I) " (being published in the Chinese medicine academic periodical of 2002 20 the 3rd phases of volume) of pharmacological room of Colleges Of Traditional Chinese Medicine Of Guangxi such as Zheng Zuowen, Deng Jiagang: MANGGUO ZHIKE PIAN obviously prolonged guinea pig Ach is drawn incubation period of breathing heavily and the contraction that resists Ach institute tracheal smooth muscle, illustrates that the antiasthmatic effect of MANGGUO ZHIKE PIAN is obvious; The sulfur dioxide of mice drawn to breathe heavily obviously to prolong cough latent period, and can reduce and stimulate cat to cough the cough number of times that epineural causes, illustrate that the antitussive effect of MANGGUO ZHIKE JIAONANG is obvious.Can obviously increase the phenol red excretion amount of mice, and have significantly and relieving asthma cough-relieving, resolve phlegm effect.

Drug efficacy study through Colleges Of Traditional Chinese Medicine Of Guangxi proves that MANGGUO ZHIKE PIAN also has obvious raising mice trachea secretory function, and resolve phlegm effect is arranged; The auricle edema due to the mouse knoting oil of obviously drawing up has antiinflammatory action; Golden staphylococcus, Diplococcus pneumoniae etc. there are inhibitory action, antibacterial action is promptly arranged.Clinical effectiveness shows, confirms through 300 routine clinical trials, and this product truly has the lung qi dispersing heat clearing away, reduces phlegm, cough-relieving, the effect of relievining asthma, and can be used to cough, the treatment of asthma, excessive phlegm.Good especially to nasal obstruction watery nasal discharge, itching throat, cough person's curative effect that flu, many types of bronchitis cause.Have advantages such as determined curative effect, steady quality.

But the inventor finds MANGGUO ZHIKE PIAN not dissolving fully after disintegrate under study for action, may cause absorption of human body efficient low, influences drug effect.The chances are because the subtractive process of the extracting solution of Folium mangiferae causes for its reason after deliberation: the one, filter, and general enterprise filter method commonly used is that 200 mesh sieves filter, may be mixed with a spot of crude drug microgranule; The 2nd, dry, barn commonly used is longer drying time, and temperature is higher, causes the paste gelatinizing and is insoluble in water, effective ingredient Yin Gaowen and losing efficacy.

Cough need be taken the preparation of instant effect as commonly encountered diseases and frequently-occurring disease when just beginning, as conventional capsule, be that disease controlling then can be taken long lasting slow releasing capsule.Because technology limitation, MANGGUO ZHIKE PIAN is a conventional tablet when the declaration drug manufacture, and relative bioavailability is lower, can not satisfy the needs of high-quality treatment disease.

Summary of the invention

The inventor in order to improve the relative bioavailability of medicine, changes oral MANGGUO ZHIKE PIAN tablet into capsule after research and testing, and by the slow releasing preparation technology, makes it to become a kind of long-acting product.

The preparation method of Fructus Mangifera Indicae cough-relieving spansule is as follows:

Fructus Mangifera Indicae cough-relieving spansule comprises the Folium mangiferae extracts active ingredients, adds Sodium Houttuyfonate and the blended processing step of chlorphenamine, with the technical characterstic of conventional tablet difference be: with the first effective component extracting of fresh Folium mangiferae, adding Sodium Houttuyfonate and chlorphenamine then mixes, make the small ball of slow release, the capsulae vacuus of packing at last, be packaged into box or be hot pressed into aluminium-plastic panel and obtain product.

The method of above-described fresh Folium mangiferae effective component extracting has water extraction, perhaps uses decoction and alcohol sedimentation technique, and perhaps water is carried and added the clarifier method, perhaps uses semi-bionic extraction, perhaps uses the semi-bionic extraction alcohol deposition method.

Above-described Folium mangiferae water extraction is that the bright leaf water of Folium mangiferae is carried 2 times, 2 hours for the first time, 1-1.5 hour for the second time, the water extract merge filter, behind the concentrate drying Fructus Mangifera Indicae cream, cold drying again, pulverize, fine powder.

Above-described Folium mangiferae decoction and alcohol sedimentation technique is that the bright leaf water of Folium mangiferae is carried secondary, 2 hours first time, 1-1.5 hour for the second time merge extractive liquid,, filtration, filtrate are concentrated into the clear paste of proportion 1.15, put cold, add ethanol, make to contain alcohol amount and reach 60%-75%, left standstill 48 hours, filter filtrate recycling ethanol, the thick paste of dense one-tenth proportion 1.25, cold drying again, pulverize, fine powder.

Above-described Folium mangiferae water carries that to add the clarifier method be that the bright leaf water of Folium mangiferae is carried secondary, 2 hours first time, 1-1.5 hour for the second time merge extractive liquid,, filtration, filtrate are concentrated into the clear paste of proportion 1.15, put cold, add clarifier, left standstill 48 hours, filter filtrate recycling ethanol, the thick paste of dense one-tenth proportion 1.25, cold drying again, pulverize, fine powder.

Described clarifier is chosen at 101 fruit juice clarifiers or chitin kind absorptive clarificant, ZTC clarifier etc., and main effect is that macromole unstability impurity such as protein, tannin, pigment and pectin reach the clarification purpose in the removal herbal liquid medicine.Addition in the clarifier is generally about 2%～20% of amount of liquid medicine.

Above-described Folium mangiferae semi-bionic extraction is that the bright leaf of Folium mangiferae is extracted 2 times with semi-bionic extraction liquid, 2 hours for the first time, 1-1.5 hour for the second time, extracting solution merged and filters, in and pH value to 7, behind the concentrate drying Fructus Mangifera Indicae cream, cold drying, pulverize, fine powder.

Above-described Folium mangiferae semi-bionic extraction alcohol deposition method is that the bright leaf of Folium mangiferae is extracted secondary with semi-bionic extraction liquid, 2 hours for the first time, 1-1.5 hour for the second time, and merge extractive liquid,, in and pH value to 7, filter, filtrate is concentrated into the clear paste of proportion 1.15, puts cold, add ethanol, make to contain alcohol amount and reach 60%-75%, left standstill 48 hours, filter filtrate recycling ethanol, the thick paste of dense one-tenth proportion 1.25, cold drying again, pulverize, fine powder.

Above-described filtration was meant 200 mesh sieves or sucking filtration.

Above-described cold drying is meant vacuum drying or lyophilization.

Above-described semi-bionic extraction liquid is meant the acid solution that is made into hydrochloric acid or acetic acid and water, also can adopt mixed acid, and acid and water preparation afterwards pH value are 2-5.

The above-described process of making the small ball of slow release is to get the chlorphenamine mix homogeneously that Sodium Houttuyfonate that the made fine powder of above-mentioned Folium mangiferae extracting method adds 5-10% by Folium mangiferae powder per kilogram adds 0.07-0.14%, add binding agent again and make microcapsule, with 10%-50% spermaceti or other blocker coating, make 2,4,6,8 hours slow-release pills respectively, every kind of piller is distinguished with different color and lusters.

Described blocker generally is divided into insoluble (as ethyl cellulose, ethylene-vinyl acetate copolymer etc.), biological dissolubility (as stearic acid, stearyl alcohol, glyceryl monostearate etc.) and a few class framework materials of hydrophilic gel (as sodium alginate, hydroxypropyl emthylcellulose etc.), can select a certain class or a few class mixtures of material and medicament mixed, make through proper method.In order to regulate the rate of releasing drug of medicine, can add porogen, surfactant.

The present invention also can be prepared into common capsule against cough, and its process is:

Get the chlorphenamine mix homogeneously that Sodium Houttuyfonate that the made fine powder of above-mentioned Folium mangiferae extracting method adds 3-20% by the Folium mangiferae powder adds 0.2-1.4%, in the capsulae vacuus of directly packing into or make in the capsulae vacuus of packing into behind the granule promptly.

The alleged Folium mangiferae of the present invention meets the crude drug of national Chinese crude drug standard for containing the Folium mangiferae of tender skill; Sodium Houttuyfonate and chlorphenamine are to meet " the crude drug of Chinese pharmacopoeia defined.

Adopting decoction and alcohol sedimentation technique mainly is to contain the alcohol amount and reach 75% when above in order to remove impurity (containing alcohol amount 50%-60%) such as destarching, to make, and removes tannin, the invalid impurity of minorities such as water colo(u)r, and all the other part impurity are all precipitable and remove.Gained extractum viscosity increases after precipitate with ethanol concentrates, and density also increases, and can make the mucilage binding of equally having mutually go into medicine, reduces and takes the capsule particle number.This is the reason that the present invention adopts alcohol deposition method.

It is same that adopt water to carry to add clarifier method purpose also be to improve drug effect in order to remove impurity, and this law to dispel the close cost of impurity effect than decoction and alcohol sedimentation technique lower.

Semi-bionic extraction process is current comparatively advanced method, and is the method for relatively economical.Its method is to imitate oral drugs at the gastrointestinal tract transport process, adopts the acid water of selected PH and alkaline water to extract continuously successively, its objective is to extract to contain high " active mixture " of mark composition that refers to Chinese crude drug.Because the process conditions of semi-bionic extraction will be fit to the reality of suitability for industrialized production, so can not be identical with people's concrete conditions in the establishment of a specific crime fully.The research of current semi-bionic extraction process about Chinese crude drug is just in the ascendant, as " the capsular semi-bionic extraction process Study on Conditions of numbness relieving and pain relieving " (Yunnan University of Traditional Chinese Medicine's journal, 2003), with " the preferred MAXINGSHIGAN TANG semi-bionic extraction process of uniform Design " (Chinese patent medicine, 2002) experimental result shows that semi-bionic extraction is better than general water extraction.The semi-bionic extraction alcohol deposition method is the development of semi-bionic extraction, and this is that the present invention adopts is the reason of semi-bionic extraction and semi-bionic extraction alcohol deposition method.

MANGGUO ZHIKE JIAONANG and Fructus Mangifera Indicae cough-relieving slow releasing capsule are the dosage changing form kinds of MANGGUO ZHIKE PIAN, it has overcome MANGGUO ZHIKE PIAN relative bioavailability and has troubled a big problem of tablet than low this, improved the relative availability of medicine, Fructus Mangifera Indicae cough-relieving slow releasing capsule also provides a kind of new thinking for the research and development of Chinese patent medicine slow releasing preparation simultaneously.

The specific embodiment

Embodiment 1

100 kilograms of fresh Folium mangiferaes are carried secondary with 10 times and 8 times of water respectively, 2 hours for the first time, 1-1.5 hour for the second time, the water extract merges after-filtration, get Fructus Mangifera Indicae cream after the concentrating low-temperature drying, pulverize to such an extent that fine powder is standby, add 0.033 kilogram Sodium Houttuyfonate by per kilogram Folium mangiferae powder then and add 0.0021 kilogram chlorphenamine mix homogeneously, add binding agent and make microcapsule, with spermaceti or other blocker coating, make 2 respectively, 4,6,8 hours slow-release pills, every kind of piller is distinguished with different color and lusters, pack into behind the mix homogeneously in the capsulae vacuus, be packaged into box or be hot pressed into aluminium-plastic panel and obtain product.

Embodiment 2

100 kilograms on the bright leaf of Folium mangiferae is carried secondary with 10 times and 8 times of water respectively, 2 hours for the first time, 1-1.5 hour collecting decoction for the second time, filter, filtrate concentrating gone back the clear paste of proportion 1.15, put cold, add ethanol, make and contain alcohol amount and reach 65%, left standstill 48 hours, filter filtrate recycling ethanol, the thick paste of dense one-tenth proportion 1.25, cold drying again, pulverize, get fine powder, add 0.05 kilogram Sodium Houttuyfonate by per kilogram Folium mangiferae powder then and add 0.0042 kilogram chlorphenamine mix homogeneously, add binding agent and make microcapsule, with spermaceti or other blocker coating, make 2 respectively, 4,6,8 hours slow-release pills, every kind of piller is distinguished with different color and lusters, in the capsulae vacuus of packing into behind the mix homogeneously, is packaged into box or is hot pressed into aluminium-plastic panel and obtain product.

Embodiment 3

100 kilograms on the bright leaf of Folium mangiferae is carried secondary with 10 times and 8 times of water respectively, 2 hours for the first time, 1-1.5 hour collecting decoction for the second time, filter, filtrate concentrating gone back the clear paste of proportion 1.15, put cold, 101 type clarifiers of adding 8%, left standstill 48 hours, filter, the thick paste of the dense one-tenth proportion 1.25 of filtrate, cold drying again, pulverize, get fine powder, add 0.05 kilogram Sodium Houttuyfonate by per kilogram Folium mangiferae powder then and add 0.0042 kilogram chlorphenamine mix homogeneously, add binding agent and make microcapsule, with spermaceti or other blocker coating, make 2 respectively, 4,6,8 hours slow-release pills, every kind of piller is distinguished with different color and lusters, pack into behind the mix homogeneously in the capsulae vacuus, be packaged into box or be hot pressed into aluminium-plastic panel and obtain product.

Embodiment 4

100 kilograms of fresh Folium mangiferaes are carried secondary with 12 times and 8 sesquialter bionic extraction liquid respectively, 1.5 hours for the first time, 1 hour for the second time, extract merges after-filtration, transfer pH value to 7, get Fructus Mangifera Indicae cream after the concentrating low-temperature drying, pulverize to such an extent that fine powder is standby, add 0.045 kilogram Sodium Houttuyfonate by per kilogram Folium mangiferae powder then and add 0.0031 kilogram chlorphenamine mix homogeneously, add binding agent and make microcapsule, with spermaceti or other blocker coating, make 3 respectively, 6,9 hours slow-release pills, every kind of piller is distinguished with different color and lusters, in the capsulae vacuus of packing into behind the mix homogeneously, is packaged into box or is hot pressed into aluminium-plastic panel and obtain product.

Embodiment 5

100 kilograms on the bright leaf of Folium mangiferae is carried secondary with 10 times and 6 sesquialter bionic extraction liquid respectively, 1.5 hours for the first time, 1 hour merge extractive liquid, for the second time, transfer pH value to 7, filter, filtrate is concentrated to the clear paste of proportion 1.15, put cold, add ethanol, make and contain alcohol amount and reach 65%, left standstill 48 hours, filter filtrate recycling ethanol, the thick paste of dense one-tenth proportion 1.25, cold drying again, pulverize, fine powder, add 0.066 kilogram Sodium Houttuyfonate by per kilogram Folium mangiferae powder then and add 0.0052 kilogram chlorphenamine mix homogeneously, add binding agent and make microcapsule, with spermaceti or other blocker coating, make 2 respectively, 4,6,8 hours slow-release pills, every kind of piller is distinguished with different color and lusters, pack into behind the mix homogeneously in the capsulae vacuus, be packaged into box or be hot pressed into aluminium-plastic panel and obtain product.

Embodiment 6

100 kilograms of fresh Folium mangiferaes are carried secondary elder generation water with 12 times and 8 times of water respectively carry secondary, 2 hours for the first time, 1-1.5 hour for the second time, the water extract gets Fructus Mangifera Indicae cream after merging after-filtration, concentrating low-temperature drying, pulverize to such an extent that fine powder is standby, add 0.033 kilogram Sodium Houttuyfonate by per kilogram Folium mangiferae powder then and add 0.0023 kilogram chlorphenamine mix homogeneously, directly pack in the capsulae vacuus, or granulate behind the mix homogeneously and pack in the capsulae vacuus, be packaged into box or be hot pressed into aluminium-plastic panel and obtain product.

Embodiment 7

100 kilograms on the bright leaf of Folium mangiferae is carried secondary water with 10 times and 8 times of water respectively carry secondary, 2 hours for the first time, 1-1.5 hour collecting decoction for the second time, filter, filtrate concentrating gone back the clear paste of proportion 1.15, put cold, add ethanol, make and contain alcohol amount and reach 65%, left standstill 48 hours, filter filtrate recycling ethanol, the thick paste of dense one-tenth proportion 1.25, cold drying again, pulverize, fine powder, add 0.066 kilogram Sodium Houttuyfonate by per kilogram Folium mangiferae powder then and add 0.0042 kilogram chlorphenamine mix homogeneously, in the capsulae vacuus of directly packing into, or granulate behind the mix homogeneously and pack in the capsulae vacuus, be packaged into box or be hot pressed into aluminium-plastic panel and obtain product.

Embodiment 8

100 kilograms on the bright leaf of Folium mangiferae is carried secondary with 12 times and 8 times of water respectively, 2 hours for the first time, 1-1.5 hour collecting decoction for the second time, filter, filtrate concentrating gone back the clear paste of proportion 1.15, put cold, add chitin kind absorptive clarificant by solution amount 5%, left standstill 48 hours, filter, the thick paste of the dense one-tenth proportion 1.25 of filtrate, cold drying again, pulverize, get fine powder, add 0.066 kilogram Sodium Houttuyfonate by per kilogram Folium mangiferae powder then and add 0.0046 kilogram chlorphenamine mix homogeneously, directly pack in the capsulae vacuus, or granulate behind the mix homogeneously and pack in the capsulae vacuus, be packaged into box or be hot pressed into aluminium-plastic panel and obtain product.

Embodiment 9

100 kilograms of fresh Folium mangiferaes are carried secondary with 12 times and 8 sesquialter bionic extraction liquid respectively, 1.5 hours for the first time, 1 hour for the second time, extract merges after-filtration, transfers pH value to 7, get Fructus Mangifera Indicae cream after the concentrating low-temperature drying, pulverize to such an extent that fine powder is standby, add 0.05 kilogram Sodium Houttuyfonate by per kilogram Folium mangiferae powder then and add 0.0033 kilogram chlorphenamine mix homogeneously, in the capsulae vacuus of directly packing into, or the capsulae vacuus intermediate package of packing into of granulating behind the mix homogeneously becomes box or is hot pressed into aluminium-plastic panel to obtain product.

Embodiment 10

100 kilograms on the bright leaf of Folium mangiferae is carried secondary with 10 times and 8 sesquialter bionic extraction liquid respectively, 1.5 hours for the first time, 1 hour merge extractive liquid, for the second time, transfer pH value to 7, filter, filtrate concentrating gone back the clear paste of proportion 1.15, put cold, add ethanol, make and contain alcohol amount and reach 65%, left standstill 48 hours, filter filtrate recycling ethanol, the thick paste of dense one-tenth proportion 1.25, cold drying again, pulverize, get fine powder, add 0.069 kilogram Sodium Houttuyfonate by per kilogram Folium mangiferae powder then and add 0.0048 kilogram chlorphenamine mix homogeneously, directly pack in the capsulae vacuus, or granulate behind the mix homogeneously and pack in the capsulae vacuus, be packaged into box or be hot pressed into aluminium-plastic panel and obtain product.

Pharmaceutical research

1, main pharmacodynamics research

In order to verify the drug effect of MANGGUO ZHIKE JIAONANG, according to above-mentioned experiment report, designed the bioequivalence experiment of MANGGUO ZHIKE PIAN and MANGGUO ZHIKE JIAONANG (plain edition), promptly MANGGUO ZHIKE JIAONANG is a matched group for the experimental group MANGGUO ZHIKE PIAN.Experimental result shows, MANGGUO ZHIKE JIAONANG is the obviously prolonged guinea pig Ach contraction of drawing tracheal smooth muscle due to incubation period of breathing heavily and the antagonism Ach also, compares with MANGGUO ZHIKE PIAN, does not have significant difference (P＜0.01) to illustrate that the MANGGUO ZHIKE JIAONANG antiasthmatic effect is obvious.Simultaneously, MANGGUO ZHIKE JIAONANG is drawn to breathe heavily to mice sulfur dioxide and can obviously be prolonged cough latent period, and can reduce and stimulate cat to cough the cough number of times that epineural causes, compares with the contrast of MANGGUO ZHIKE PIAN, does not have significant difference (P＜0.01); MANGGUO ZHIKE JIAONANG also can reduce the cough number of times that stimulates the cat superior laryngeal nerve to cause, illustrates that the antitussive effect of MANGGUO ZHIKE JIAONANG is obvious.MANGGUO ZHIKE JIAONANG also can obviously increase the phenol red excretion amount of mice, compare with MANGGUO ZHIKE PIAN, there is not significant difference (P＜0.01), illustrate that the effect of MANGGUO ZHIKE JIAONANG thinner expectorant is obvious. above-mentioned experimental results show that MANGGUO ZHIKE JIAONANG also have significantly relieving asthma, cough-relieving, resolve phlegm effect, comparing with matched group does not have significant difference.The clean fruit of above-mentioned experiment shows that MANGGUO ZHIKE JIAONANG is not less than MANGGUO ZHIKE PIAN at least on curative effect.

2, pharmacokinetic

Because the chemical constituent of Chinese patent medicine is very complicated, the inventor is representative with this single composition of contained Sodium Houttuyfonate in the preparation MANGGUO ZHIKE JIAONANG, has carried out the in vitro study of the pharmacokinetics of this medicine.Various chemical active ingredients in this prescription should be collaborative additions, so can be inferred the pharmacokinetics of this product by the pharmacokinetics of Sodium Houttuyfonate.The inventor has designed the dissolution in vitro experiment of medicine.Dissolution refers to main effective ingredient dissolution rate and degree in the regulation medium in the preparation, is a kind of disintegrate of oral solid formulation in gastrointestinal tract and in vitro tests method of stripping simulated.In general between the bioavailability positively related relation is arranged in dissolution in vitro and the body.So can test by dissolution in vitro and verify bioavailability evaluation in the medicine body, can be used as a kind of method of bioequivalence verification experimental verification simultaneously.

Experimental result shows that the burst size of the burst size of 60 minutes Sodium Houttuyfonate of MANGGUO ZHIKE PIAN and 10 minutes Sodium Houttuyfonate of MANGGUO ZHIKE JIAONANG is suitable.Suppose can reach in 2.5 or 3 hours the blood drug level peak of this product, this moment, total burst size of MANGGUO ZHIKE PIAN Sodium Houttuyfonate was respectively 66% and 72% of MANGGUO ZHIKE JIAONANG.The Bioavailability of Human Body of above-mentioned experimental result explanation MANGGUO ZHIKE JIAONANG obviously is better than MANGGUO ZHIKE PIAN, illustrates that also the treatment speed of MANGGUO ZHIKE JIAONANG is obviously faster than MANGGUO ZHIKE PIAN simultaneously.Therefore can infer tentatively that also the blood drug level peak value of MANGGUO ZHIKE PIAN is about 70% of a MANGGUO ZHIKE JIAONANG, therefore under same dose, every clothes 3 capsules can be equivalent to 4 tablets.

About Fructus Mangifera Indicae cough-relieving slow releasing capsule, the inventor adopts spermaceti that Fructus Mangifera Indicae cough-relieving piller has been carried out coating, and these slow-release pills have been carried out external appearance out-degree experiment, and all slow-release pills all begin to discharge Sodium Houttuyfonate after the slow-release time of regulation.Above experimental result shows can obviously slow down the release of the Sodium Houttuyfonate in the MANGGUO ZHIKE PIAN, thereby reaches long lasting purpose.

Clinical data

The traditional Chinese medical science is diagnosed as wind-heat invading lung type cough, and Western medicine diagnose is that voluntary patient 17 examples of acute upper respiratory tract infection are treated with MANGGUO ZHIKE JIAONANG and Fructus Mangifera Indicae cough-relieving slow releasing capsule.The treatment initial stage is used MANGGUO ZHIKE JIAONANG, treat that the state of an illness is alleviated to some extent after, reuse Fructus Mangifera Indicae cough-relieving slow releasing capsule, and decrement were gradually observed after seven days, cured 13 examples, effective 4 examples.The result shows this product determined curative effect.

Claims (10)

1, a kind of preparation method of Fructus Mangifera Indicae cough-relieving spansule, comprise that Folium mangiferae extracts, adds Sodium Houttuyfonate and the blended processing step of chlorphenamine, it is characterized in that: with the first effective component extracting of fresh Folium mangiferae, adding Sodium Houttuyfonate and chlorphenamine then mixes, make the small ball of slow release, the capsulae vacuus of packing at last, be packaged into box or be hot pressed into aluminium-plastic panel and obtain product;

2, the preparation method of Fructus Mangifera Indicae cough-relieving spansule according to claim 1, it is characterized in that: described extracting method adopts water extraction, its step is that the bright leaf water of Folium mangiferae is carried 2 times, 2 hours for the first time, 1-1.5 hour for the second time, the water extract merge to filter, behind the concentrate drying Fructus Mangifera Indicae cream, cold drying again, pulverize, fine powder.

3, the preparation method of Fructus Mangifera Indicae cough-relieving spansule according to claim 1, it is characterized in that: described decoction and alcohol sedimentation technique method is that the bright leaf water of Folium mangiferae is carried secondary, it is 1.15 clear paste that 2 hours for the first time, 1-1.5 hour for the second time merge extractive liquid,, filtration, filtrate are concentrated into proportion, put coldly, add ethanol, make to contain the alcohol amount and reach 65%, left standstill 48 hours, filter filtrate recycling ethanol, dense one-tenth proportion is 1.25 thick paste, cold drying again, pulverize, fine powder.

4, the preparation method of Fructus Mangifera Indicae cough-relieving spansule according to claim 1, it is characterized in that: described water carries that to add the clarifier method be that the bright leaf water of Folium mangiferae is carried secondary, 2 hours first time, 1-1.5 hour for the second time merge extractive liquid,, filtration, filtrate are concentrated into the clear paste of proportion 1.15, put cold, add clarifier, left standstill 48 hours, filter filtrate recycling ethanol, the thick paste of dense one-tenth proportion 1.25, cold drying again, pulverize, fine powder.

5, the preparation method of Fructus Mangifera Indicae cough-relieving spansule according to claim 1, it is characterized in that: described semi-bionic extraction is the bright leaf of Folium mangiferae to be got with semi-bionic extraction liquid carry 2 times, 2 hours for the first time, 1-1.5 hour for the second time, extracting solution merges filtration, in and pH value to 7, behind the concentrate drying Fructus Mangifera Indicae cream, cold drying, pulverize, fine powder.

6, the preparation method of Fructus Mangifera Indicae cough-relieving spansule according to claim 1, it is characterized in that: described semi-bionic extraction alcohol deposition method is that the bright leaf of Folium mangiferae is extracted secondary with semi-bionic extraction liquid, 2 hours for the first time, 1-1.5 hour merge extractive liquid, for the second time, in and pH value to 7, filter, filtrate is concentrated into the clear paste of proportion 1.15, put cold, add ethanol, make to contain alcohol amount and reach 60%-75%, left standstill 48 hours, filter filtrate recycling ethanol, the thick paste of dense one-tenth proportion 1.25, cold drying again, pulverize, fine powder.

7, according to the preparation method of the described Fructus Mangifera Indicae cough-relieving of claim 1-6 spansule, it is characterized in that: described filtration was meant 200 mesh sieves or sucking filtration; Described cold drying is meant vacuum drying or lyophilization.

8, according to the preparation method of claim 5 and 6 described Fructus Mangifera Indicae cough-relieving spansules, it is characterized in that: described semi-bionic extraction liquid is meant that the pH value with hydrochloric acid or acetic acid or mixed acid and water preparation is the acid solution of 2-5.

9, according to the preparation method of the described Fructus Mangifera Indicae cough-relieving of claim 1-6 spansule, it is characterized in that: the process of the small ball of described system slow release is to get the chlorphenamine mix homogeneously that Sodium Houttuyfonate that the made fine powder of above-mentioned Folium mangiferae extracting method adds 5-20% by Folium mangiferae powder per kilogram adds 0.07-0.14%, add binding agent and make microcapsule, with 10%-50% spermaceti or other blocker coating, make 2,4,6,8 hours slow-release pills respectively, every kind of piller is distinguished with different color and lusters.

10, a kind of preparation method of MANGGUO ZHIKE JIAONANG, it is characterized in that: its preparation process is: the Sodium Houttuyfonate that the made fine powder of Folium mangiferae effective component extracting is added 3-20% by the Folium mangiferae powder adds the chlorphenamine mix homogeneously of 0.2-1.4%, in the capsulae vacuus of directly packing into or make the capsulae vacuus of packing into behind the granule and promptly get common capsule against cough.