CN101181347A - Pastille soft capsule and preparation method thereof - Google Patents

Abstract

The invention provides a novel soft capsule of Lamiophlomis rotate, which includes base material, suspending agent, wetting agent and surface active agent. The soft capsule is capable of overcoming the problems of disintegration delay of the existing preparation; meanwhile, the soft capsule is also capable of remarkably enhancing the benefit effect of the Lamiophlomis rotate preparation. Compared with the existing products in the market, the invention has the advantages of remarkable stability and curative effect.

Description

A kind of pastille soft capsule and preparation method thereof

Technical field

The present invention relates to a kind of medicinal soft capsule preparation that contains Radix Lamiophlomidis Rotatae extract, it can significantly strengthen the beneficial effect of said preparation.

Background technology

The present listing dosage form of Radix Lamiophlomidis Rotatae is tablet, capsule, granule, can ease pain, stop blooding.After water is proposed, add appropriate amount of auxiliary materials preparation and get by the Radix Lamiophlomidis Rotatae medical material.The preparation shortcoming of granule comes into plain view, each oral consumption is big, take after mixing it with water after needing to melt with boiled water earlier, and the bitterness of medicine own is very heavy, this dosage is big, mouthfeel difference and take the administering mode of inconvenience, and carries inconvenience or the like and very easily cause the patient to use poor compliance; And granule is difficult for storing very easily moisture absorption microbiological contamination and then mouldy.For many years production and clinical practice prove that existing Radix Lamiophlomidis Rotatae hard capsule and Radix Lamiophlomidis Rotatae sheet exist certain defective, and for example, bioavailability is low; The useful life is short, phenomenons such as the content deliquescence easily takes place long-term storage, the in bulk that hardens; And affected by environment in actual use big, often promptly inefficacy or character are defective before the deadline; The smell is awful for tablet, compliance difference of pain patients or the like.

The inventor becomes soft capsule with Radix Lamiophlomidis Rotatae according to the said extracted prepared, have bioavailability height, good airproof performance, content accurately, good looking appearance, cover bad smell, the patient is easy to take and makes its compliance good, do not add simultaneously correctivess such as saccharide in the soft capsule, make the life-time service that diabetics can be relieved.

Usually, the substrate of soft capsule is divided into vegetable oil and Polyethylene Glycol, because Polyethylene Glycol is a water-soluble base, at soft capsule between the storage life, be partly dissolved the water soluble ingredient in the soft capsule shell, especially for the relatively thinner place of soft capsule seam, in case the content leaks phenomenon will take place in dissolving, this also is that those skilled in the art face the insurmountable so far difficult problem of Polyethylene Glycol substrate.

It is the content substrate of Duyiwei soft capsule that the inventor selects vegetable oil through the research back.Radix Lamiophlomidis Rotatae is made soft capsule, though dosage form has improved, but need overcome a lot of difficulties, for example disintegrate becomes and material migration, effective ingredient generation sedimentation and content composition seepage equistability problem takes place in defective, the capsule in soft capsule storage period of prior art.To those skilled in the art, these problems are difficult to expect.

As everyone knows, producing medicine from the pharmaceutical factory generally will experience to the process that consumer uses: production, warehouse-in, pharmaceutical factory storage, transportation, distributor's storage, pharmacy or hospital put on the shelf after picking up goods, consumer buys, consumer uses in expiration date of drug.The Duyiwei soft capsule that utilizes prior art so and obtained is except keeping the cryogenic desirable environment of preserving in storage, other links all become the unfavorable factor that influences disintegrate, and the Duyiwei soft capsule product of above-mentioned prior art can't overcome above unfavorable factor, this just inevitably brings product disintegrate before the deadline defective, influence pharmaceutical effectiveness and can't reach therapeutic purposes, illustrate that the scheme of prior art instruction obtains the Duyiwei soft capsule product, its ubiquity effect duration is short, disintegrate is defective, necessary cryopreservation (still lack under the low temperature by effect duration, disintegrate is defective), producing, inevitable defective on transportation and the sales section.

Though the Duyiwei soft capsule product is arranged in the market, but in view of the problem that occurs in the complexity of Radix Lamiophlomidis Rotatae extract its own particularity matter and physicochemical property and the clinical practice thereof, up to now also how we overcome the existing above-mentioned all problems of Duyiwei soft capsule preparation without any teach literature, also have no talent and the beneficial effect of the soft capsule that comprises Radix Lamiophlomidis Rotatae are provided the prediction of science.

Therefore, this area presses for the Radix Lamiophlomidis Rotatae oral Pharmaceutical dosage forms that exploitation makes new advances, and said preparation should be reduced to bottom line with its negative effect when effectively improving product stability.This pharmaceutical dosage form can improve patient's treatment compliance, and must be safe.

Summary of the invention

The invention provides a kind of containing with the soft capsule of Radix Lamiophlomidis Rotatae extract as active component, it in the solution of success in the ubiquitous common problem of present soft capsule preparation, for example As time goes on disintegrate prolongs, can also significantly strengthen the beneficial effect of Radix Lamiophlomidis Rotatae, remarkable stability and treatment advantage be arranged than present commercially available prod.

The object of the present invention is to provide a kind of Duyiwei soft capsule pharmaceutical preparation, the soft capsule preparation that particularly contains Radix Lamiophlomidis Rotatae, it has overcome the defective of existing Radix Lamiophlomidis Rotatae oral formulations, and overcome defective, the interior problem that material migration, effective ingredient sedimentation and content composition seepage equistability difference take place of capsule of disintegrate that soft capsule usually occurs, and strengthened the beneficial effect of Radix Lamiophlomidis Rotatae.Simultaneously, adopt the method for external test drug effect, adopt the soft capsule of method preparation of the present invention to compare with the soft capsule sample of art methods preparation, effect of drugs has had and has significantly improved.In addition, the invention provides a kind of selection, it provides a kind of new safety product as the substituting of prior art, and this dosage form will be the approval that the doctor recommends to use and obtain doctor and patient.

The invention provides a kind of soft capsule that contains Radix Lamiophlomidis Rotatae extract, be made up of the content and the capsule material of soft capsule, the content of this soft capsule contains Radix Lamiophlomidis Rotatae extract, vegetable oil, suspending agent, surfactant; Radix Lamiophlomidis Rotatae extract wherein: vegetable oil: suspending agent: the part by weight of surfactant is 1: 0.05～5: 0.05～1: 0.01～1;

Above-mentioned substrate is vegetable oil, is selected to be one or more mixture in Oleum Sesami, Oleum Arachidis hypogaeae semen, Semen Maydis oil, olive oil, Oleum Helianthi, soybean oil, salad oil, Oleum Gossypii semen, the Oleum Brassicae campestris; One or more mixture in preferred soybean oil, Semen Maydis oil, Oleum Brassicae campestris, the salad oil.More preferably one or both mixture in Semen Maydis oil, the soybean oil.

Suspending agent is the conventional suspending agent in this area, is selected from mainly that Cera Flava, Cera Flava, white beeswax, mixing are cured, one or more mixture in the Petiolus Trachycarpi oil, hydrogenated palm oil, hydrogenation silk floss oil, tristerin, aluminum monostearate, glyceryl monostearate, fatty glyceride, mixed fatty glycerides; One or more mixture in preferred Cera Flava, Petiolus Trachycarpi oil, hydrogenated palm oil, glyceryl monostearate, the mixed fatty glycerides; The more preferably a kind of or mixture in Cera Flava, the hydrogenated palm oil.

Surfactant is a tween, preferred tween 80.

The content of the soft capsule of the invention described above contains 20～70% Radix Lamiophlomidis Rotatae extract at least.

The part by weight of active component Radix Lamiophlomidis Rotatae extract and vegetable oil is 1: 0.05～5, preferred 1: 0.2～4, more preferably 1: 0.5～2.

The part by weight of active component Radix Lamiophlomidis Rotatae extract and suspending agent is 1: 0.05～1, preferred 1: 0.08～0.8, more preferably 1: 0.1～0.5.

The part by weight of active component Radix Lamiophlomidis Rotatae extract and surfactant is 1: 0.01～1, preferred 1: 0.02～0.8, more preferably 1: 0.03～0.5.

Described Radix Lamiophlomidis Rotatae extract can be prepared according to the step method under the Radix Lamiophlomidis Rotatae medicinal material extract item in the Radix Lamiophlomidis Rotatae capsule in the version pharmacopeia in 2000, is for example made by following method: get the Radix Lamiophlomidis Rotatae medical material, pulverize, decoct with water, decocting liquid filters, and filtrate concentrates after drying, pulverize, promptly.Method for optimizing is: get the Radix Lamiophlomidis Rotatae medical material, pulverize, decoct with water 3 times, each 1 hour, collecting decoction filtered, and it is 1.30 clear paste that filtrate is condensed into relative density, and drying is pulverized and promptly got Radix Lamiophlomidis Rotatae extract.

For the more effective clinical effectiveness that improves preparation that reaches, more advantageously active component is carried out pretreatment, comprising described Radix Lamiophlomidis Rotatae extract is ground into pulverizing in advance, be the above fine powder of 80 orders, more than preferred 100 orders, more preferably more than 120 orders, even micronization.

Favourable, Radix Lamiophlomidis Rotatae extract is mixed with surfactant fully, for example: tween.

The present invention also provides a kind of method for preparing above-mentioned Duyiwei soft capsule, comprising:

1) get Radix Lamiophlomidis Rotatae extract, pulverizing becomes 80 order fine powders at least.

2) get tween 80, add above-mentioned raw materials, fully mix to few 20 minutes, standby.

3) get vegetable oil, add suspending agent, heating makes its fusion, stirs, and cools to 30～50 degree, stirs once more, and is standby.

4) with 3) join 2) in, after stirring, after colloid mill grinds several times excessively, if be pressed into soft capsule after having bubble to add defoamer.

The method of Duyiwei soft capsule, comprising:

1) get Radix Lamiophlomidis Rotatae extract, pulverizing becomes 80 order fine powders at least.

2) get tween 80, add above-mentioned raw materials, fully mix to few 20 minutes, standby.

3) get vegetable oil, add suspending agent, heating makes its fusion, stirs, and cools to 30～50 degree, stirs once more, and is standby.

4) with 3) join 2) in, after stirring, if be pressed into soft capsule after having bubble to add defoamer.

More favourable, Radix Lamiophlomidis Rotatae extract is mixed fully with surfactant and wetting agent, for example: tween and phospholipid.

The method of Duyiwei soft capsule, comprising:

1) get Radix Lamiophlomidis Rotatae extract, pulverizing becomes 80 order fine powders at least.

2) get the homogeneous mixture solotion of tween 80 and soybean phospholipid, add above-mentioned raw materials, fully mix to few 20 minutes, standby.

3) get vegetable oil, add suspending agent, heating makes its fusion, stirs, and cools to 30～50 degree, stirs once more, and is standby.

4) with 3) join 2) in, after stirring, if be pressed into soft capsule after having bubble to add defoamer.

It can be single-matrixes such as vegetable oil, Polyethylene Glycol that prior art is instructed the substrate of our soft capsule, adds the content that suspending agent or lubricant etc. are formed soft capsule in addition.

The soft capsule that with the Polyethylene Glycol is substrate is commonplace usually, and the extraction process that Radix Lamiophlomidis Rotatae extract adopts water to carry wherein contains a large amount of water soluble ingredients; Test finds that the Duyiwei soft capsule that with the Polyethylene Glycol is the substrate preparation is after placing a period of time, and the water soluble ingredient in the extract can be transferred in the softgel shell along with the migration of moisture in the content, thereby causes the degeneration of softgel shell and cause disintegrate to postpone; Simultaneously because Polyethylene Glycol is a water-soluble base, with composition in the soft capsule shell mutual dissolved ability is arranged, especially the seam crossing that approaches partially for soft capsule shell causes content constantly to leak; Just at Radix Lamiophlomidis Rotatae extract involved in the present invention, nearly all be not the ubiquitous common problem of soft capsule of substrate with the Polyethylene Glycol to this problem.So it is substrate that the present invention adopts vegetable oil.

With regard to simple vegetable oil substrate, also exist many difficulties that are difficult to overcome in the soft capsule field, wherein the character of therapeutic component is most important to the quality influence of soft capsule finished product in the content, mainly there are problems such as leakage of oil, content layering, these can adopt the granularity of the minimizing extract particles of instructing in handbook or the document and rationally screen suspending agent and overcome, and for example discuss " the soft capsule oil impregnate problem that improvement contains Chinese medicine extract " in the document; But for prolonged disintegration, this difficult problem but is an insurmountable up to now difficult problem.Though people such as Ma Xu just studied soft capsule prolonged disintegration phenomenon influence factor in 2003, but the phenomenon of prolonged disintegration is not obviously improved, and the existence of this phenomenon has caused this advantage dosage form of soft capsule can't increase the purpose that the medicine stripping reaches the raising drug effect.

Through a large amount of creationary exploratory experiments, the inventor finds, adds an amount of surfactant in the soft capsule, can specifically, unexpectedly solve the existing problem of Duyiwei soft capsule.Therefore, the soft capsule that contains surfactant has constituted pith of the present invention, and just this composite interstitial substance of surfactant and vegetable oil has played the mutual promoting action that those skilled in the art can't imagine.The inventor is in a large amount of groping in the experiment of the present invention, analyzing the mechanism of selecting quantitative surfactant obviously to improve the quality of Duyiwei soft capsule is: Radix Lamiophlomidis Rotatae extract contains a large amount of flavones ingredients, for the oleaginous base of soft capsule field routine, these compositions show as more hydrophilic (being that water solublity is better), and contain at least 10% moisture in the soft capsule skin, the existence of these moisture can guide Flavonoid substances slowly to be transferred to the soft capsule Intradermal, thus the disintegrate that prolongs soft capsule with cross linking of gelatin; The adding of surfactant has changed the character of content, content and capsule shell intermediate formation layer protecting film, stop or delayed the transfer of flavones ingredient to capsule shell, thus the disintegrate of having protected the intrinsic property of gelatin self to prolong soft capsule.

As the improvement of dosage form, the present invention finds through overtesting, selects suitable Radix Lamiophlomidis Rotatae extract and substrate, and the suitable proportioning of Radix Lamiophlomidis Rotatae extract and surfactant, makes up then, can obtain the remarkable enhanced soft capsule of stability.For choice of base, the present invention has done a large amount of screening experiment, simultaneously with prior art be that the soft capsule of substrate compares test with simple vegetable oil.The part by weight of final definite active component Radix Lamiophlomidis Rotatae extract and vegetable oil is 1: 0.05～5, preferred 1: 0.2～4, more preferably 1: 0.5～2; The part by weight of active component Radix Lamiophlomidis Rotatae extract and surfactant is 1: 0.05～5, preferred 1: 0.08～3, more preferably 1: 0.1～2.

The inventor adopts the method for regulation under 2005 editions two relevant appendix items of Chinese Pharmacopoeia to carry out slaking test, the Duyiwei soft capsule that it is substrate that test specimen is respectively simple employing vegetable oil (sample A), and to adopt vegetable oil and surfactant mixture be the Duyiwei soft capsule (sample B) of composite interstitial substance.The result is as follows in the sample slaking test:

Experimental condition

The sampling and measuring time (unit: month)

		Test specimen	0	1	2	3	6	12	18	24
											Accelerated test	37 ℃, the RH70% climatic chamber	Sample A	13 minutes	19 minutes	32 minutes	102 minutes	＞120 minutes	---	---	---
Sample B	10 minutes	15 minutes	22 minutes	54 minutes	76 minutes	---	---	---
									The room temperature test	25 ℃, the RH60% climatic chamber			Sample A	13 minutes	12 minutes	17 minutes	36 minutes	＞120 minutes	---	---	---
Sample B	10 minutes	11 minutes	10 minutes	12 minutes	30 minutes	36 minutes	39 minutes	52 minutes

According to the product that scheme obtained of prior art instruction, the disintegrate in 3 months of 37 ℃ of accelerated tests is just defective, and the effect duration of prompting product is very short, substantially in 1 year; And room temperature test disintegrate in 6 months is defective; And adopting the disintegration time of product accelerated test in the time of 3 months that the present invention obtained to shorten fully near 1 hour than sample A, 25 degree room temperatures keep sample and can keep in 2 years disintegrate qualified.

Above-mentioned test data suffices to show that and adopts the product that the present invention obtained, and has solved long-term puzzlement those skilled in the art's a difficult problem, has obtained beyond thought technological break-through.

The inventor also puts forth effort on the effect that can significantly improve medicine when pursuing the high Duyiwei soft capsule product of stability.This also is the final target of pursuing of the inventor, and a kind of product is stable, the outstanding Duyiwei soft capsule clinical prods of reliable quality effect of drugs for extensive patients provides.The inventor attempts to adopt another kind of the selection, soon Radix Lamiophlomidis Rotatae extract dry powder keeps smaller particle size to satisfy the requirement that fast Absorption improves drug effect in the body as far as possible in the soft capsule of the present invention, for example, a kind of for to achieve the goal by superfine powder (90% above particle diameter is less than 5um); Another kind method is in the process of superfine powder extract, suitably add the conventional means and the method that can increase dissolution according to solid preparation, for example, with extract and surfactant or water soluble adjuvant superfine powder, promote the surfactant such as the sodium lauryl sulphate of stripping, promote the water soluble adjuvant such as the lactose of stripping, the particle diameter of the microgranule that obtains behind the ultra micro more than 90% all less than 5um; Regrettably, do not obtain satisfied effect equally.

The a large amount of creative test of process is groped and is screened, the discovery that the inventor is surprised, and the adding of surfactant tween has obtained unexpected effect, has significantly improved the effect of drugs of Duyiwei soft capsule.

The preparation of soft capsule method of conventional oil substrate is earlier suspending agent and surfactant to be joined in the pyritous vegetable oil, after fusing/thawing or the dispersion, treats that temperature reduces the back and adds wetting agent, and then active component is added wherein, stirs.

Find in the test, Zhi Bei Duyiwei soft capsule according to the method described above, curative effect of medication is compared effect of drugs with existing common lamiophlomis root preparation and is not significantly improved.And adopt Radix Lamiophlomidis Rotatae extract is dispersed in earlier in the tween, the oleaginous base that will contain suspending agent again adds wherein, stirs, and can obtain beyond thought effect.This effect is to adopt external test Duyiwei soft capsule method of dissolution to realize.

But, be not that just everything is just fine as long as Radix Lamiophlomidis Rotatae extract is dispersed in earlier in the tween, find also in the test that jitter time is close with the strong or weak relation that obtains external bacteriostasis.

After the two simple mixing, add the oleaginous base that contains suspending agent immediately, the dissolution result is equal to and does not add tween.

Radix Lamiophlomidis Rotatae extract is distributed in the tween, stirred 10 minutes, add the oleaginous base that contains suspending agent, measure dissolution 63%.

Radix Lamiophlomidis Rotatae extract is distributed in the tween, stirred 20 minutes, add the oleaginous base that contains suspending agent, measure dissolution 87%.

Radix Lamiophlomidis Rotatae extract is distributed in the tween, stirred 30 minutes, add the oleaginous base that contains suspending agent, measure dissolution 92%.

Radix Lamiophlomidis Rotatae extract is distributed in the tween, stirred 60 minutes, add the oleaginous base that contains suspending agent, measure dissolution 94%.

Favourable, Radix Lamiophlomidis Rotatae extract to be mixed with surfactant fully, incorporation time must not be less than 20 minutes.

The method for preparing above-mentioned Duyiwei soft capsule, comprising:

1) get Radix Lamiophlomidis Rotatae extract, pulverizing becomes 80 order fine powders at least.

2) get tween 80, add above-mentioned raw materials, fully mix to few 20 minutes, standby.

3) get vegetable oil, add suspending agent, heating makes its fusion, stirs, and cools to 30～50 degree, stirs once more, and is standby.

4) with 3) join 2) in, after stirring, after colloid mill grinds several times excessively if necessary, if after having bubble to add defoamer, be pressed into soft capsule.

The inventor finds in the experiment in a large amount of groping of the present invention, the effect of surfactant is wetting agent and the simple dispersive effect in the bibliographical information absolutely not, analyzing the mechanism of selecting quantitative surfactant obviously to improve the effect of drugs of Duyiwei soft capsule is: the adding of surfactant, make and originally become compatible mutually with the very inconsistent Radix Lamiophlomidis Rotatae extract of vegetable oil, strengthened the synergism of the two, surfactant and Radix Lamiophlomidis Rotatae extract form a kind of complex of high degree of dispersion in oleaginous base simultaneously, this complex runs into after the Digestive system in entering body, the state of a kind of emulsifying of very fast formation or even self emulsifying, this state has improved absorption and the utilization of body to active component greatly, thereby shows as significantly improving of drug effect.

The adding method of the wetting agent of the soft capsule of conventional oil substrate is earlier suspending agent to be joined in the pyritous vegetable oil, after fusing/thawing or the dispersion, treats that temperature reduces the back and adds wetting agent, and then active component is added wherein, stirs.Because the special role of surfactant and creative using method and setup time among the present invention, and the unique effect of being brought into play in soft capsule is different fully with prior art, test is a prerequisite with test method of the present invention, has investigated the difference between the product that the difference adding method of wetting agent obtained.

Sample preparation methods 1: Radix Lamiophlomidis Rotatae extract is distributed to earlier in the tween solution, stirred 30 minutes, add the vegetable oil substrate that contains suspending agent, stir.

Sample preparation methods 2: Radix Lamiophlomidis Rotatae extract is distributed to earlier in the tween solution, stirred 30 minutes, add the vegetable oil substrate that contains suspending agent, after stirring, add wetting agent, stir.

Sample preparation methods 3: after Radix Lamiophlomidis Rotatae extract being dispersed in the mixed solution of tween and wetting agent earlier, stirred 30 minutes, the vegetable oil substrate that will contain suspending agent again adds wherein, stirs.

The discovery that the inventor is surprised in test, sample 1 and 2 dissolution in vitro measurement result are approaching, and adopt the Duyiwei soft capsule sample of preparation method 3 preparations, and the dissolution determination result of acquisition is more unexpected, improves at least 7% than sample 1 and 2.

Wherein above-mentioned Radix Lamiophlomidis Rotatae extract: the part by weight of wetting agent is 1: 0.01～0.5, preferred 1: 0.02～0.2, more preferably 1: 0.03～0.1; Wetting agent is a phospholipid, arbitrary or its combination in preferred soybean phospholipid, lecithin, the egg yolk lecithin; More preferably soybean phospholipid.

Favourable, Radix Lamiophlomidis Rotatae extract to be mixed with surfactant fully, incorporation time must not be less than 20 minutes.

More favourable, Radix Lamiophlomidis Rotatae extract to be mixed fully with surfactant and wetting agent, incorporation time must not be less than 20 minutes, for example: tween and soybean phospholipid.

The method for preparing above-mentioned Duyiwei soft capsule, comprising:

1) get Radix Lamiophlomidis Rotatae extract, pulverizing becomes 80 order fine powders at least.

2) get the homogeneous mixture solotion of tween 80 and soybean phospholipid, add above-mentioned raw materials, fully mix to few 20 minutes, standby.

3) get vegetable oil, add suspending agent, heating makes its fusion, stirs, and cools to 30～50 degree, stirs once more, and is standby.

4) with 3) join 2) in, after stirring, cross colloid mill, if be pressed into soft capsule after having bubble to add defoamer.

The inventor has remarkable hemostasis and analgesic effect for more favourable explanation product of the present invention, adopts the test of pesticide effectiveness and animal model further to verify the curative effect of medication of product of the present invention.

Hemostasis trial

It is experimental animal that mice is adopted in test, behind the gastric infusion 3 days, adopt the relatively anastalsis at each position of docking hemostasis and capillary tube blood coagulation method, measure mice docking bleeding time and clotting time respectively, thereby the power of the anastalsis of indirect reaction product, the anastalsis of the short more explanation product of bleeding time and clotting time is also strong.

Trial drug:

Sample 1: commercially available Radix Lamiophlomidis Rotatae hard capsule.

Sample 2: Radix Lamiophlomidis Rotatae extract is joined the vegetable oil substrate that contains suspending agent, after stirring, the compacting soft capsule.

Sample 3: Radix Lamiophlomidis Rotatae extract is distributed to earlier in the tween solution, stirred 30 minutes, add the vegetable oil substrate that contains suspending agent, stir, the compacting soft capsule.

Sample 4: after Radix Lamiophlomidis Rotatae extract being dispersed in the mixed solution of tween and wetting agent earlier, stirred 30 minutes, the vegetable oil substrate that will contain suspending agent again adds wherein, stirs the compacting soft capsule.

Result of the test: each sample sets all has therapeutic effect.Each strong and weak order of organizing anastalsis is followed successively by: sample 4＞sample 3＞sample 1＞sample 2.

Tween is as surfactant, be used to pharmaceutical field for a long time, tween haemolysis problem for public's worry, clear and definite hemolytic test is the inspection item that is used for estimating the injection safety in the pharmacological testing rules, haemolysis is to occur in the drug administration by injection process, and there is not the haemolysis problem in oral formulations.In order to eliminate the worry of the public for the safety of tween, the inventor has done acute toxicity test simultaneously with the checking security of products.。

Acute toxicity test

Experimental animal is the mice of male and female half and half, is test specimen with above-mentioned sample 3, and mice daily dose dosage is equivalent to 150 times of human dosage, and 2 weeks were observed in the back of taking medicine, and all experimental animals are all normal, does not have dead the generation.Acute toxicity test shows that product of the present invention has no side effect.

Above-mentioned result of the test proves absolutely, Duyiwei soft capsule among the present invention, with the soft capsule that adopts prior art for preparing, be in vivo or the external beyond thought drug effect and the quality of the pharmaceutical preparations of all having obtained, compare with the Radix Lamiophlomidis Rotatae hard capsule, (cover the serious bitterness of Radix Lamiophlomidis Rotatae extract having reached many advantages of soft capsule, loading amount is accurate, appearance looks elegant and steady quality, be easy to take and carry or the like) in addition, obtained satisfied clinical efficacy more, satisfied those skilled in the art and looked forward to all the time and can obtain than the eager hope in high-drug-effect ground by adopting advanced preparation means.

Its specification of Duyiwei soft capsule of the present invention generally can be divided into 0.4～0.9g/ grain, and clinical recommendation consumption is 2～10g/ day.

The present invention has following characteristic: good storing stability, and the deliquescence and the deterioration of preparation are suppressed, and active component preparation characteristics such as speed of stripping from preparation do not change, and overcome a series of defectives of existing product.More advantageously be, preparation of the present invention has been covered the disagreeable taste of Radix Lamiophlomidis Rotatae fully, can also improve the taste of Chinese medicine preparation, and quantitatively accurately, even also can be easily under anhydrous situation,, have significantly improved the compliance of patient to treatment without any the administration of uncomfortable ground.

To further make non restrictive description below to the present invention.

Active component

In context, the Radix Lamiophlomidis Rotatae extract among the present invention promptly is active component (effective site), and this active component is the Radix Lamiophlomidis Rotatae extract that meets the Chinese medicine ministry standard.Described Radix Lamiophlomidis Rotatae extract can prepare voluntarily, also can sell by the merchant and buy.

Soft capsule content:

Described inclusions is meant the active component in the soft capsule (or claim soft gelatin capsule) and/or is carried on active component in the excipient, and wherein content can following arbitrary state and exist.In view of the special requirement of inflammation treatment, the present invention especially preferably provides the content of suspension or emulsion-type to prepare soft capsule dosage form.This is because the Radix Lamiophlomidis Rotatae active component that is carried in substrate and/or the excipient has dispersibility highly, has effectively improved its bioavailability.

Pharmaceutical composition provided by the invention, it contains the Radix Lamiophlomidis Rotatae extract and the conventional medicine adjuvant of clinical treatment effective dose.

The preparation of soft capsule method

The present invention does not make specific limited to the preparation method of Duyiwei soft capsule, can adopt this area conventional method, for example pressing or dropping preparation method (drop pill method).

Soft capsule rubber adopts disclosed composition of handbook and compound method, except glue, plasticizer and water, can add pigment, opacifier, antiseptic or acid-base modifier etc. simultaneously.

The specific embodiment

Embodiment 1: the preparation of Radix Lamiophlomidis Rotatae extract

Get the Radix Lamiophlomidis Rotatae medical material, pulverize, decoct with water 3 times, each 1 hour, collecting decoction filtered, and it is 1.30 clear paste that filtrate is condensed into relative density, dry below 80 ℃, Radix Lamiophlomidis Rotatae extract.

Embodiment 2:

Radix Lamiophlomidis Rotatae extract: 0.25g

Soybean oil: 0.09g

Tween 80: 0.09g

Cera Flava: 0.005g

Hydrogenated palm oil: 0.01g

Soybean phospholipid: 0.005g

Make 1 (0.45g)

Preparation technology

Get the tween 80 and the soybean phospholipid of recipe quantity, be stirred well to mix homogeneously, as stock solution 1.

Get the Radix Lamiophlomidis Rotatae extract among the embodiment 1, be ground into and can cross 200 mesh sieves and get fine powder, join in the above-mentioned stock solution 1, fully disperse to stir, jitter time must not be less than 20 minutes, as stock solution 2.

Get the soybean oil of recipe quantity, add Cera Flava and hydrogenated palm oil, heating makes the suspending agent fusion, stirs, and cools to 50 degree; Solution is poured in the above-mentioned stock solution 2, is stirred once more, cross colloid mill, if bubble is arranged, add defoamer in right amount after, be pressed into soft capsule.

Embodiment 3:

Radix Lamiophlomidis Rotatae extract: 0.25g

Semen Maydis oil: 0.20g

Tween 80: 0.025g

Cera Flava: 0.005g

Hydrogenated palm oil: 0.01g

Soybean phospholipid: 0.01g

Make 1 (0.5g)

Preparation technology

Get the tween 80 and the soybean phospholipid of recipe quantity, be stirred well to mix homogeneously, as stock solution 1.

Get the Radix Lamiophlomidis Rotatae extract among the embodiment 1, be ground into and can cross 180 mesh sieves and get fine powder, join in the above-mentioned stock solution 1, fully disperse to stir, jitter time must not be less than 20 minutes, as stock solution 2.

Get the Semen Maydis oil of recipe quantity, add Cera Flava and hydrogenated palm oil, heating makes the suspending agent fusion, stirs, and cools to 45 degree; Solution is poured in the above-mentioned stock solution 2, is stirred once more, cross colloid mill, if bubble is arranged, add defoamer in right amount after, be pressed into soft capsule.

Embodiment 4:

Radix Lamiophlomidis Rotatae extract: 0.25g

Semen Maydis oil: 0.23g

Tween 80: 0.02g

Cera Flava: 0.02g

Hydrogenated palm oil: 0.015g

Soybean phospholipid: 0.015g

Make 1 (0.55g)

Preparation technology

Get the tween 80 and the soybean phospholipid of recipe quantity, be stirred well to mix homogeneously, as stock solution 1.

Get the Radix Lamiophlomidis Rotatae extract among the embodiment 1, be ground into and can cross 120 mesh sieves and get fine powder, join in the above-mentioned stock solution 1, fully disperse to stir, jitter time must not be less than 20 minutes, as stock solution 2.

Get the Semen Maydis oil of recipe quantity, add Cera Flava and hydrogenated palm oil, heating makes the suspending agent fusion, stirs, and cools to 45 degree; Solution is poured in the above-mentioned stock solution 2, is stirred once more, cross colloid mill, if bubble is arranged, add defoamer in right amount after, be pressed into soft capsule.

Embodiment 5

Radix Lamiophlomidis Rotatae extract: 0.25g

Soybean oil: 0.25g

Tween 80: 0.05g

Cera Flava: 0.025g

Hydrogenated palm oil: 0.025g

Make 1 (0.6g)

Preparation technology

Get the Radix Lamiophlomidis Rotatae extract among the embodiment 1, be ground into and can cross 100 mesh sieves and get fine powder, join the tween 80 of recipe quantity, fully disperse to stir, jitter time must not be less than 20 minutes, as stock solution 1.

Get the soybean oil of recipe quantity, add Cera Flava and hydrogenated palm oil, heating makes the suspending agent fusion, stirs, and cools to 40 degree; Solution is poured in the above-mentioned stock solution 1, is stirred once more, cross colloid mill, if bubble is arranged, add defoamer in right amount after, be pressed into soft capsule.

Embodiment 6

Radix Lamiophlomidis Rotatae extract: 0.20g

Soybean oil: 0.24g

Tween 80: 0.01g

Cera Flava: 0.015g

Hydrogenated palm oil: 0.025g

Soybean phospholipid: 0.01g

Make 1 (0.5g)

Preparation technology

Get the tween 80 and the soybean phospholipid of recipe quantity, be stirred well to mix homogeneously, as stock solution 1.

Get the Radix Lamiophlomidis Rotatae extract among the embodiment 1, be ground into micropowder, its granularity all less than 10um, joins in the above-mentioned stock solution 1 more than 90%, fully disperses to stir, and jitter time must not be less than 20 minutes, as stock solution 2.

Get the soybean oil of recipe quantity, add Cera Flava and hydrogenated palm oil, heating makes the suspending agent fusion, stirs, and cools to 50 degree; Solution is poured in the above-mentioned stock solution 2, is stirred once more, cross colloid mill, if bubble is arranged, add defoamer in right amount after, be pressed into soft capsule.

Embodiment 7

Radix Lamiophlomidis Rotatae extract: 0.20g

Salad oil: 0.29g

Tween 80: 0.01g

Cera Flava: 0.06g

Hydrogenated palm oil: 0.04g

Make 1 (0.6g)

Preparation technology

Get the Radix Lamiophlomidis Rotatae extract among the embodiment 1, be ground into and can cross 80 mesh sieves and get fine powder, join the tween 80 of recipe quantity, fully disperse to stir, jitter time must not be less than 20 minutes, as stock solution 1.

Get the salad oil of recipe quantity, add Cera Flava and hydrogenated palm oil, heating makes the suspending agent fusion, stirs, and cools to 40 degree; Solution is poured in the above-mentioned stock solution 1, is stirred once more, cross colloid mill, if bubble is arranged, add defoamer in right amount after, be pressed into soft capsule.

Embodiment 8

Radix Lamiophlomidis Rotatae extract: 0.25g

Semen Maydis oil: 0.22g

Tween 80: 0.13g

Cera Flava: 0.015g

Hydrogenated palm oil: 0.015g

Soybean phospholipid: 0.02g

Make 1 (0.65g)

Preparation technology

Get the tween 80 and the soybean phospholipid of recipe quantity, be stirred well to mix homogeneously, as stock solution 1.

Get the Radix Lamiophlomidis Rotatae extract among the embodiment 1, be ground into and can cross 150 mesh sieves and get fine powder, join in the above-mentioned stock solution 1, fully disperse to stir, jitter time must not be less than 20 minutes, as stock solution 2.

Get the Semen Maydis oil of recipe quantity, add Cera Flava and hydrogenated palm oil, heating makes the suspending agent fusion, stirs, and cools to 45 degree; Solution is poured in the above-mentioned stock solution 2, is stirred once more, cross colloid mill, if bubble is arranged, add defoamer in right amount after, be pressed into soft capsule.

Embodiment 9

Radix Lamiophlomidis Rotatae extract: 0.25g

Oleum Sesami: 0.35g

Tween 80: 0.02g

Cera Flava: 0.18g

Make 1 (0.8g)

Preparation technology

Get the Radix Lamiophlomidis Rotatae extract among the embodiment 1, be ground into and can cross 80 mesh sieves and get fine powder, join the tween 80 of recipe quantity, fully disperse to stir, jitter time must not be less than 20 minutes, as stock solution 1.

Get the Oleum Sesami of recipe quantity, add Cera Flava, heating makes the suspending agent fusion, stirs, and cools to 35 degree; Solution is poured in the above-mentioned stock solution 1, is stirred once more, cross colloid mill, if bubble is arranged, add defoamer in right amount after, be pressed into soft capsule.

Embodiment 10

Radix Lamiophlomidis Rotatae extract: 0.125g

Oleum Brassicae campestris: 0.16g

Tween 80: 0.1g

Glyceryl monostearate: 0.06g

Hydrogenated palm oil: 0.04g

Soybean phospholipid: 0.015g

Make 1 (0.5g)

Preparation technology

Get the tween 80 and the soybean phospholipid of recipe quantity, be stirred well to mix homogeneously, as stock solution 1.

Get the Radix Lamiophlomidis Rotatae extract among the embodiment 1, be ground into and can cross 80 mesh sieves and get fine powder, join in the above-mentioned stock solution 1, fully disperse to stir, jitter time must not be less than 20 minutes, as stock solution 2.

Get the Oleum Brassicae campestris of recipe quantity, add glyceryl monostearate and hydrogenated palm oil, heating makes the suspending agent fusion, stirs, and cools to 35 degree; Solution is poured in the above-mentioned stock solution 2, is stirred once more, cross colloid mill, if bubble is arranged, add defoamer in right amount after, be pressed into soft capsule.

Embodiment 11

Radix Lamiophlomidis Rotatae extract: 0.125g

Salad oil: 0.47g

Tween 80: 0.04g

Glyceryl monostearate: 0.115

Make 1 (0.75g)

Preparation technology

Get the Radix Lamiophlomidis Rotatae extract among the embodiment 1, be ground into and can cross 80 mesh sieves and get fine powder, join the tween 80 of recipe quantity, fully disperse to stir, jitter time must not be less than 20 minutes, as stock solution 1.

Get the salad oil of recipe quantity, add glyceryl monostearate oil, heating makes the suspending agent fusion, stirs, and cools to 35 degree; Solution is poured in the above-mentioned stock solution 1, is stirred once more, cross colloid mill, if bubble is arranged, add defoamer in right amount after, be pressed into soft capsule.

Embodiment 12

Radix Lamiophlomidis Rotatae extract: 0.30g

Semen Maydis oil: 0.20g

Tween 80: 0.02g

Hydrogenated palm oil: 0.025g

Lecithin: 0.01g

Make 1 (0.55g)

Preparation technology

Get the tween 80 and the lecithin of recipe quantity, be stirred well to mix homogeneously, as stock solution 1.

Get the Radix Lamiophlomidis Rotatae extract among the embodiment 1, be ground into micropowder, its granularity all less than 5um, joins in the above-mentioned stock solution 1 more than 90%, fully disperses to stir, and jitter time must not be less than 20 minutes, as stock solution 2.

Get the Semen Maydis oil of recipe quantity, add hydrogenated palm oil, heating makes the suspending agent fusion, stirs, and cools to 45 degree; Solution is poured in the above-mentioned stock solution 2, is stirred once more, cross colloid mill, if bubble is arranged, add defoamer in right amount after, be pressed into soft capsule.

Embodiment 13

Radix Lamiophlomidis Rotatae extract: 0.30g

Soybean oil: 0.265g

Tween 80: 0.03g

Cera Flava: 0.02g

Hydrogenated palm oil: 0.015g

Fabaceous lecithin: 0.02g

Make 1 (0.65g)

Preparation technology

Get the tween 80 and the fabaceous lecithin of recipe quantity, be stirred well to mix homogeneously, as stock solution 1.

Get the Radix Lamiophlomidis Rotatae extract among the embodiment 1, be ground into and can cross 280 mesh sieves and get fine powder, join in the above-mentioned stock solution 1, fully disperse to stir, jitter time must not be less than 20 minutes, as stock solution 2.

Get the soybean oil of recipe quantity, add Cera Flava and hydrogenated palm oil, heating makes the suspending agent fusion, stirs, and cools to 50 degree; Solution is poured in the above-mentioned stock solution 2, is stirred once more, cross colloid mill, if bubble is arranged, add defoamer in right amount after, be pressed into soft capsule.

More than described the preferred embodiment for the present invention, so it is not in order to limit the present invention.Those skilled in the art can not depart from the improvement and the variation of category of the present invention and spirit to embodiment disclosed herein.

Claims (12)

1. Duyiwei soft capsule, it is 20～70% Radix Lamiophlomidis Rotatae extract, vegetable oil, suspending agent and surfactant that the content that it is characterized in that this soft capsule contains percentage by weight, and described Radix Lamiophlomidis Rotatae extract: vegetable oil: suspending agent: the part by weight of surfactant is 1: 0.05～5: 0.05～1: 0.01～1.

2. Duyiwei soft capsule as claimed in claim 1, wherein Radix Lamiophlomidis Rotatae extract: vegetable oil: suspending agent: the part by weight of surfactant is 1: 0.2～4: 0.08～0.8: 0.02～0.8.

3. the described Duyiwei soft capsule of claim 1～2, wherein Radix Lamiophlomidis Rotatae extract: vegetable oil: suspending agent: the part by weight of surfactant is 1: 0.5～2: 0.1～0.5: 0.03～0.5.

4. each described Duyiwei soft capsule of claim 1～3, wherein said Radix Lamiophlomidis Rotatae extract is made by following method:

Get the Radix Lamiophlomidis Rotatae medical material, pulverize, decoct with water, decocting liquid filters, and filtrate concentrates after drying, pulverizes, promptly.

5. the described Duyiwei soft capsule of claim 1～3, wherein said vegetable oil is one or more mixture in Oleum Sesami, Oleum Arachidis hypogaeae semen, Semen Maydis oil, olive oil, Oleum Helianthi, soybean oil, salad oil, Oleum Gossypii semen, the Oleum Brassicae campestris; One or more mixture in preferred soybean oil, Semen Maydis oil, Oleum Brassicae campestris, the salad oil.More preferably one or both mixture in Semen Maydis oil, the soybean oil.

6. the described Duyiwei soft capsule of claim 1～3, wherein said suspending agent are selected from that Cera Flava, Cera Flava, white beeswax, mixing are cured, one or more mixture in the Petiolus Trachycarpi oil, hydrogenated palm oil, hydrogenation silk floss oil, tristerin, aluminum monostearate, glyceryl monostearate, fatty glyceride, mixed fatty glycerides; One or more mixture in preferred Cera Flava, Petiolus Trachycarpi oil, hydrogenated palm oil, glyceryl monostearate, the mixed fatty glycerides; The more preferably a kind of or mixture in Cera Flava, the hydrogenated palm oil.

7. the described Duyiwei soft capsule of claim 1～3, wherein said surfactant is selected from tween.

8. the described Duyiwei soft capsule of claim 1～3 contains wetting agent.

9. the described Duyiwei soft capsule of claim 8, wherein Radix Lamiophlomidis Rotatae extract: the part by weight of wetting agent is 1: 0.01～0.5, preferred 1: 0.02～0.2, more preferably 1: 0.03～0.1.

10. the described wetting agent of claim 7 is a phospholipid, arbitrary or its combination in preferred soybean phospholipid, lecithin, the egg yolk lecithin; More preferably soybean phospholipid.

11. the preparation method of the described Duyiwei soft capsule of claim 1～3 is characterized by:

1) get Radix Lamiophlomidis Rotatae extract, pulverizing becomes 80 order fine powders at least.

2) get surfactant, with above-mentioned 1) fine powder fully disperse wherein, the dispersed with stirring time must not be less than 20 minutes.

3) get vegetable oil, add suspending agent, heating makes the suspending agent fusion, stirs, and cools to 30～50 degree, stirs.

4) with 3) join 2) in, after fully stirring, cross colloid mill, if be pressed into soft capsule after having bubble to add defoamer.

12. the preparation method of the described Duyiwei soft capsule of claim 1～9 is characterized by:

1) get Radix Lamiophlomidis Rotatae extract, pulverizing becomes 80 order fine powders at least.

2) get surfactant and wetting agent, with above-mentioned 1) fine powder fully disperse wherein, the dispersed with stirring time must not be less than 20 minutes.

3) get vegetable oil, add suspending agent, heating makes the suspending agent fusion, stirs, and cools to 30～50 degree, stirs.

4) with 3) join 2) in, after stirring, cross colloid mill, if be pressed into soft capsule after having bubble to add defoamer.