CN102048860B - A kind of soft capsule for nasosinusitis pharmaceutical preparation and preparation method thereof - Google Patents
A kind of soft capsule for nasosinusitis pharmaceutical preparation and preparation method thereof Download PDFInfo
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- CN102048860B CN102048860B CN201010608681.1A CN201010608681A CN102048860B CN 102048860 B CN102048860 B CN 102048860B CN 201010608681 A CN201010608681 A CN 201010608681A CN 102048860 B CN102048860 B CN 102048860B
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Abstract
A kind of soft capsule for nasosinusitis pharmaceutical preparation treating rhinitis and nasosinusitis and preparation method thereof.With Chinese medicine Fructus Xanthii, Flos Magnoliae, Radix Rubiae, Flos Chrysanthemi Indici, Flos Lonicerae as raw material, extracted rear a certain proportion of vegetable oil, soybean lecithin and the Cera Flava of adding, the soft capsule preparation of compacting.The present invention uses supercritical carbon dioxide method to extract volatile oil, extracts yield than existing vapor distillation and hot water return method high 1～3%；Content adds soybean lecithin, improves the mobility of content, reduce the leakage ball rate (less than 0.1 ‰) of product；By adjusting capsule shells component ratio, improve be long placed in rear softgel shell hardening become fragile, the problem of not easy disintegrating, and make aesthetic in appearance generous.
Description
Technical field
The invention belongs to technical field of Chinese medicines, be specifically related to a kind of soft gelatin pharmaceutical preparation for treating rhinitis and sinusitis and
Its preparation method.
Technical background
Chronic rhinitis, sinusitis are one of department of otorhinolaryngology commonly encountered diseases, frequently-occurring disease, the traditional Chinese medical science belongs to " stuffy nose ", " heap soil or fertilizer over and around the roots nose ",
" nasal sinusitis " category.Nasal sinusitis, refers to turbid nasal discharge, and as the nether world oozes, amount is the cacorhinia of principal character the most incessantly, normal companioned with headache,
Nasal obstruction, hyposmia, nasal sinuses district pain, the most empty dizzy endlessly.In contemporary Chinese medicine and pharmacy, the primary treatment principle of nasal sinusitis is " to dredge
Wind, heat clearing away, dampness removing ", concerted application of drugs " rising based on pungent taste and dissipate, lay equal stress on by bitter and middle the sweet of emergency of pathogenic fire purging；Heat clearing away cold expelling is double to be executed ".
Drug main used to have: Fructus Xanthii, Flos Magnoliae, Flos Lonicerae, Flos Chrysanthemi Indici etc..
The listing kind of current treatment " nasal sinusitis " has nasal sinusitis sheet, sinusitis pill and nasal sinusitis syrup etc., and (see being loaded in, " the China people are altogether
With state's the Sanitation Ministry medicine standard Traditional Chinese medicine historical preparation (the 6th) ")." Drug Standard of Ministry of Public Health of the Peoples Republic of China Chinese traditional patent formulation system
Agent (the 6th) " in the prescription of " nasal sinusitis sheet " be " Fructus Xanthii 672g, Flos Magnoliae 126g, Flos Lonicerae 42g, Radix Rubiae 42g, open country
Flos Chrysanthemi 42g, makes 1000, each takes 6～8 ".
In nasal sinusitis tablet preparation, once take sheet number more, not very convenient；Additionally its raw extract be mainly volatile oil and
Alcohol soluble composition, specific examples of such components is not only suitable for preparing Chinese medicinal soft capsule, and is conducive to this type of to become because of soft capsule preparation feature
Its pharmacological activity is waved in distribution；Furthermore, in nasal sinusitis preparation, to be that a class is important, have pungent temperature dissipate the active site of effect with volatile oil；
Due to soft capsule good airproof performance, and volatile oil is miscible in carrier oil solution, and the volatile oil in former preparation only sprays and is adsorbed in admittedly
Shape thing, soft capsule dosage form is conducive to keeping stability and the pharmacologically active of specific examples of such components, and therefore nasal sinusitis preparation is more suitable for making
Become soft capsule.
It addition, soft capsule dosage form has dosage accurately, easy to carry and use, the features such as bioavailability is high, good looking appearance,
Increasingly favored by consumer.Product about nasal sinusitis class soft gelatin pharmaceutical preparation is few, patent of invention " soft capsule for nasosinusitis
And preparation method thereof " (number of patent application: 200410040987.6), and patent of invention " soft capsule medicament for treating nasosinusitis and preparation thereof
Method " (number of patent application 200510001982.7) describe formula and the manufacture method of soft capsule for nasosinusitis, it is substantially with plant
Oil is substrate, and volatile oil Chinese medicine extraction obtained and extract powder add stirring and prepare content, are then pressed into soft capsule.But
At present soft capsule for nasosinusitis there is also certain weak point:
1) soft capsule content formula.The dry powder hygroscopicity that raw material Chinese medicine water extraction obtains is stronger, after making content in proportion
Relatively thickness, mobility is the best, leakage ball phenomenon easily occurs, and finished product yield is relatively low；
2) the dry powder hygroscopicity also obtained because of raw material Chinese medicine water extraction is stronger, easily draws the moisture in capsule shells after pelleting,
Cause capsule shells water content to decline, cause product to be placed a period of time, capsule shells because moisture reduce and become fragile, hardening, collapse
Solve duration, after taking, be unfavorable for digesting and assimilating of product.This is also Chinese medicine extraction species soft capsule common problem；
3) raw material extraction process.During extracting Flos Magnoliae, Flos Lonicerae, three kinds of volatility of raw material oil of Flos Chrysanthemi Indici, typically use hot water
Backflow or steam distillation, these method extraction time length, loss of volatile oil are big, and extraction efficiency ratio is relatively low.
For the deficiency of current soft capsule for nasosinusitis, the present invention by improving raw material extraction process, the formula of Suitable content thing, change
Soft capsule shell composition proportion, makes material effective component to make full use of, and soft gel products yield is high, and leakage ball phenomenon is few；Capsule
Shell is difficult to hardening becoming fragile, good looking appearance, it is easy to disintegrate and absorption.
Summary of the invention
It is an object of the invention to optimize soft capsule for nasosinusitis raw material extraction process, improve that existing product pelleting occurs leakage ball is many, disintegrate
The problems such as difficulty.
The present invention is a kind of soft capsule for nasosinusitis pharmaceutical preparation, is to be with Chinese medicine Fructus Xanthii, Flos Magnoliae, Radix Rubiae, Flos Chrysanthemi Indici, Flos Lonicerae
Raw material, extracted rear a certain proportion of vegetable oil, soybean lecithin and the Cera Flava of adding, the soft capsule preparation of compacting.
This soft capsule content component composition with part by weight is, soybean lecithin: Cera Flava: vegetable oil: Chinese medicine (Fructus Xanthii,
Flos Magnoliae, Radix Rubiae, Flos Chrysanthemi Indici, Flos Lonicerae) extract (including volatile oil)=1: 1～2: 30～40；10～20.
This soft capsule capsule shells component composition with part by weight is, gelatin: purified water: glycerol: ethyl hydroxybenzoate: rose-red: deep
Chocolate palm fibre: titanium dioxide=1.0: 0.82～1.1: 0.45～0.55: 0.0005～0.0015: 0.0004～0.0008: 0.001～0.003:
0.001～0.003.
Wherein:
Chinese medicine (Flos Magnoliae, Flos Chrysanthemi Indici, Flos Lonicerae) used in this soft capsule content extracts the preparation method of volatile oil and faces for super
Boundary's carbon dioxide extraction prepares.
The extracting parameter of volatile oil is:
Flos Magnoliae, Flos Chrysanthemi Indici, Flos Lonicerae raw material by weight 3: 1: 1, be crushed to 20-60 mesh, carries out supercritical two after being simply mixed
Carbonoxide extracts.Extraction kettle temperature 30～60 DEG C, pressure 15～35MPa；Separating still temperature 15～30 DEG C, pressure 4～8MPa；
Extraction time 1.5～3.5 hours, flow of carbon dioxide gas amount 15～30Kg/h；
Remaining extracts and presses the extract dry powder that in pharmacopeia, nasal sinusitis sheet method prepares:
1) Radix Rubiae, uses 70% ethanol as solvent, carries out seepage pressure effects after impregnating 24 hours；
2) Fructus Xanthii is added above supercritical carbon dioxide volatile oil step is extracted in remaining medicinal residues, extract through boiling
3 times, filtration, merging filtrate, concentration, add alcohol and filter, filtrate is extracted gained percolation with Radix Rubiae and is filtered liquid and merge, and reclaims ethanol,
Drying is pulverized and is prepared dry powder.
The method preparing soft capsule for nasosinusitis, comprises the following steps:
1) content is prepared
1. the volatile oil that Flos Magnoliae, Flos Lonicerae, Flos Chrysanthemi Indici extract is mixed with less than the vegetable oil of 10 times of weight, stirring and evenly mixing；
2. Cera Flava is added in the vegetable oil of 3～15 times of weight, is heated to 70～80 DEG C and melts, be subsequently adding the vegetable oil of surplus,
Stir, let cool to less than 45 DEG C；
3. by the volatile oil 1. obtained and the mixture of vegetable oil, the soybean lecithin of formula ratio and (Flos Magnoliae, Flos Lonicerae,
Flos Chrysanthemi Indici) extract the residue after volatile oil and extract dry powder that Fructus Xanthii, Radix Rubiae are prepared by nasal sinusitis sheet method in pharmacopeia, add
2. in the oily wax mixture prepared, stirring while adding, mixing；The solution of mixing crosses 80～120 eye mesh screens after colloid mill grinds,
Obtain content feed liquid.
2) prepared by glue
By the purified water of formula ratio, glycerol (reserve and be used for a little mixing colours), ethyl hydroxybenzoate additionization glue tank, heated and stirred.Heating
To adding gelatin during suitable temperature, continue stirring, treat gelatin fusing and be mixed into all with ethyl hydroxybenzoate, glycerol, purified water
After even glue, evacuation while stirring, to glue bubble-free.
Weigh the deep chocolate palm fibre of formula ratio, rose-red, titanium dioxide, mix with the glycerol reserved when changing glue, put into colloid
Grinding uniformly in mill, be then added in the glue of above-mentioned preparation, stirring is to glue color even, the glue that must prepare.
3) pelleting
Glue is made into rubber by soft capsule pellet press, content is added material bin and carries out pelleting.
4) shape, be dried
The soft capsule body just suppressed is softer, carries out cooling and shaping, and is dried.
The invention have the characteristics that
1) problem existed according to character and the existing soft capsule pelleting of raw extract, adds a certain proportion of in content
Soybean lecithin, improves the mobility of content, makes product be easier to pelleting, and product leakage ball rate is reduced to less than 0.1 ‰,
Rate improves.
2) in order to prevent due to the water translocation in capsule shells or too fast scatter and disappear cause that capsule shells is hardening, become fragile, not easy disintegrating, this
Invention research have adjusted the ratio of gelatin in capsule shells, G & W, improves the character of softgel shell, and with the addition of in capsule shells
Pigment, titanium dioxide, make product design more beautiful, generous, and beneficially the stablizing of product content thing.
3) present invention is during volatile oil is extracted in research products material (Flos Magnoliae, Flos Lonicerae, Flos Chrysanthemi Indici), uses supercritical
The method of carbon dioxide abstraction, the yield of volatile oil improves 1～3 percentage point.And extraction rate is fast, efficiency is high, extracts
During relative temperature low, be conducive to preserving the active component in medical material.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is further elaborated:
Embodiment 1
1) volatile oil is extracted
The parameter of supercritical carbon dioxide extraction volatile oil is: by dry raw material Flos Magnoliae 93.75kg, Flos Lonicerae 31.25kg, open country
Flos Chrysanthemi 31.25kg is crushed to 40 mesh, loads supercritical carbon dioxide extraction still after mixing in batches, adjusts extraction kettle temperature 50 C,
Pressure 25MPa；Separating still temperature 15 DEG C, pressure 8MPa；Adjust flow of carbon dioxide gas amount 20 ± 5Kg/h in pipeline, enter
Row volatile oil extracts.Extraction time 2.5 hours, volatile oil about 480g under the conditions of this, yield 3.1%, steam than general steam
Evaporate high with hot water return method yield.
2) prepared by soft capsule for nasosinusitis product
The method of preparation soft capsule for nasosinusitis described in claim 1, comprises the following steps:
(1) content is prepared
1. by above-mentioned 1) gained Flos Magnoliae, Flos Lonicerae, Flos Chrysanthemi Indici extract volatile oil mix with soybean oil 4kg, stirring and evenly mixing；
2. Cera Flava 3kg is added 15kg soybean oil, after 70～80 DEG C add heat fusing, add soybean oil 53.5kg, stir；
3. by the volatile oil obtained in 1. and vegetable oil mixt, 2kg soybean lecithin, to prepare by nasal sinusitis sheet method in pharmacopeia
Extract dry powder about 23.7kg, add 2. in prepare oily wax mixture in, stirring while adding, mixing；The solution warp of mixing
Colloid mill crosses 80 eye mesh screens after grinding, and obtains content feed liquid.
(2) prepared by glue
By 49.0kg water, 22.25kg glycerol (having reserved 2kg for mixing colours), 49.5g ethyl hydroxybenzoate additionization glue tank, heating
Stirring.Add 49.5kg gelatin when being heated to suitable temperature, continue stirring, treat gelatin fusing and with ethyl hydroxybenzoate, glycerol,
After purified water is mixed into uniform glue, evacuation while stirring, to glue bubble-free.
Weigh 99g deep chocolate palm fibre, 36g rose-red, 99g titanium dioxide, mix with the 2kg glycerol reserved when changing glue, put
Entering in colloid mill and grind uniformly, add in the glue of above-mentioned preparation, stirring is to glue color even, the glue that must prepare.
(3) pelleting
Glue is made into rubber by soft capsule pellet press, content is added material bin and carries out pelleting, 0.6g/ grain.
(4) shape, be dried, pick ball, packaging
The soft capsule body just suppressed is softer, and rotating cage cooling and shaping is after 2 hours, at temperature 18～26 DEG C, humidity 20～35% ring
Under border, after static dry 24 hours, reject special-shaped ball, big piller, bubble ball, flat ball etc., carry out product packaging, the most prepared
Finished product.
Being produced product by above production stage, in production process, soft gel products yield is 96.2%, and leakage ball rate is less than 0.1 ‰, raw
Produce stable smooth.Through this product carries out the inspections such as content uniformity, microorganism, heavy metal, disintegration, result meets quality inspection
Standard inspection is accurate.It addition, according to the feature of product, through stability test detection, (temperature is 37-40 to the product of three batches of Packing Sounds of production
DEG C, place 3 months under the conditions of relative humidity 5%, 0 month and placement process monthly detect once), product refers to disintegration
Mark, equal conformance with standard.Concrete outcome is as follows:
Index situation of change in table 1 soft capsule for nasosinusitis product stability process of the test
As can be seen from Table 1, after the accelerated placement of product of the present invention 3 months, what disintegration was most only extend 5min, three
Batch product is without the biggest difference, and capsule shells does not has the hardening phenomenon that becomes fragile.These all illustrate intact the solving of formula for a product of the present invention
At present soft capsule for nasosinusitis deposits the problem that capsule shells after placement hardening becomes fragile, disintegration extends, and process stabilizing is feasible.
Embodiment 2
1) volatile oil is extracted
The parameter of supercritical carbon dioxide extraction volatile oil is: by dry raw material Flos Magnoliae 75kg, Flos Lonicerae 25kg, Flos Chrysanthemi Indici 25kg
It is crushed to 20 mesh, after mixing, loads supercritical carbon dioxide extraction still in batches, adjust extraction kettle temperature 35 DEG C, pressure 30MPa；
Separating still temperature 20 DEG C, pressure 6MPa；Adjust flow of carbon dioxide gas amount 25 ± 5Kg/h in pipeline, carry out volatile oil extraction.
Extraction time 2 hours, volatile oil about 377g under the conditions of this, yield 3.0%.
2) prepared by soft capsule for nasosinusitis product
(1) content is prepared
1. Flos Magnoliae, Flos Lonicerae, Flos Chrysanthemi Indici are extracted the volatile oil about 377g that obtains mix with safflower oil 2kg, stirring and evenly mixing；
2. Cera Flava 1kg is added in 8kg safflower oil, heat 70～80 DEG C and melt, add safflower oil 25kg, stir；
3. by the volatile oil obtained in 1. and the extract dry powder of vegetable oil mixt, 1kg soybean lecithin and above-mentioned steps
18.9kg, in the oily wax mixture prepared in adding 2., stirring while adding, mixing；The solution of mixing is mistake after colloid mill grinds
80 eye mesh screens, obtain content feed liquid.
2) prepared by glue
By 49.5kg water, 20.25kg glycerol (having reserved 2kg for mixing colours), 48g ethyl hydroxybenzoate additionization glue tank, heating is stirred
Mix.Add 49.5kg gelatin when being heated to suitable temperature, continue stirring, treat gelatin fusing and with ethyl hydroxybenzoate, glycerol, pure
After change water is mixed into uniform glue, evacuation while stirring, to glue bubble-free.
Weigh 90g deep chocolate palm fibre, 33g rose-red, 90g titanium dioxide, mix with the 2kg glycerol reserved when changing glue, put
Entering in colloid mill and grind uniformly, add in the glue of above-mentioned preparation, stirring is to glue color even, the glue that must prepare.
3) pelleting, shape, be dried, pick ball, packaging: with embodiment 1.
Claims (1)
1. a soft capsule for nasosinusitis pharmaceutical preparation, be with Chinese medicine Fructus Xanthii 672g, Flos Magnoliae 126g, Radix Rubiae 42g, Flos Chrysanthemi Indici 42g, Flos Lonicerae 42g ratio as raw material, a certain proportion of vegetable oil, soybean lecithin and Cera Flava, the soft capsule preparation of compacting is added after extracted；
It is characterized in that soft capsule content component composition and part by weight are: soybean lecithin: Cera Flava: vegetable oil: Chinese medicine extract=1: 1.5: 36.25: 11.25；Described Chinese medicine extract is the Fructus Xanthii including volatile oil, Flos Magnoliae, Radix Rubiae, Flos Chrysanthemi Indici, Flos Lonicerae extract；Wherein: Flos Magnoliae, Flos Chrysanthemi Indici, the preparation method of Flos Lonicerae extract are supercritical carbon dioxide extraction method；Concrete grammar parameter is: Flos Magnoliae, Flos Chrysanthemi Indici, Flos Lonicerae raw material are the most size-reduced to 20-60 mesh；Supercritical carbon dioxide extraction parameter is: extraction kettle temperature 30～60 DEG C, pressure 15～35MPa；Separating still temperature 15～30 DEG C, pressure 4～8MPa；Extraction time 1.5～3.5 hours, flow of carbon dioxide gas amount 15～30Kg/h；The preparation method of Madder extract is Radix Rubiae 70% ethanol as solvent, carries out seepage pressure effects after impregnating 24 hours；The preparation method of Fructus Xanthii extract is extracted in remaining medicinal residues for being added by Fructus Xanthii in above supercritical carbon dioxide volatile oil step, extract 3 times through boiling, filtration, merging filtrate, concentration, add alcohol to filter, filtrate and Radix Rubiae are extracted gained percolation liquid of filtering and merge, reclaiming ethanol, drying is pulverized and is prepared dry powder；
Its capsule shells component composition with part by weight is: gelatin: purified water: glycerol: ethyl hydroxybenzoate: rose-red: deep chocolate palm fibre: titanium dioxide=1.0: 1.0: 0.50: 0.001: 0.00072: 0.002: 0.002.
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| CN105106347A (en) * | 2015-06-26 | 2015-12-02 | 重庆医科大学 | Semen ziziphi spinosae soft capsules and preparation method thereof |
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