CN102293794A - Subing pill preparation and preparation thereof - Google Patents
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- CN102293794A CN102293794A CN2010102063134A CN201010206313A CN102293794A CN 102293794 A CN102293794 A CN 102293794A CN 2010102063134 A CN2010102063134 A CN 2010102063134A CN 201010206313 A CN201010206313 A CN 201010206313A CN 102293794 A CN102293794 A CN 102293794A
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Abstract
The invention relates to a solid dispersoid medicinal preparation and discloses a Subing pill preparation and preparation thereof. The Subing pill preparation comprises medicinal ingredients and auxiliary materials, wherein based on the total mass of the auxiliary materials, the auxiliary materials comprise the following ingredients in percentage by mass: 57 to 86 percent of polyethylene glycol and 14 to 43 percent of polyoxyethylene(40)stearate. The invention breaks through the technical barrier that the original Subing pill cannot embody the basic characteristics of the solid dispersion preparation and restores the due features of the modern solid dispersing agent, so that the dissolution and dispersion (or disintegration) time limit measured by a cradling method can meet the technical requirement formulated by 'Chinese Pharmacopoeia' after 2005 edition without a baffle.
Description
Technical field
The present invention relates to solid dispersion pharmaceutical preparation, be specifically related to Chinese medicine preparation Subing drop pills preparation and preparation thereof.
Background technology
Drop pill is a kind of solid dispersion (Soild dispertion).So-called solid dispersion is meant that material dispersed (comprising various states of matters) is dispersed in a kind of compounding substances that solid state medium forms, material dispersed can the dispersion with the state of molecule, ionic or microgranule wherein.Solid dispersion is widely used in modern pharmaceutical as a kind of drug-supplying system, behind solid or liquid medicine and the substrate heat fused mixing, splashes in the not miscible condensed fluid, shrinks condensation and the preparation made, mainly supplies oral application.This dripping method pelletizing process is actually the form of solid dispersion being made drop pill.
The dropping preparation method pill starts from vitamin A, the D ball of Denmark's pharmaceutical factory preparation in 1933.Domesticly start from 1958, in recent years, the application of synthetic, semi-synthetic substrate and solid dispersion technology makes drop pill that development rapidly arranged, and has particularly obtained very big development in the exploitation of new product of Chinese medicine." Chinese pharmacopoeia version in 1977 takes the lead in recording drops, nineteen ninety-five, version recorded 9 kinds of drop pills, version in 2000, version in 2005 and version in 2010 are obvious increases, kind surplus the Chinese medicine dripping pills authentication code of existing State Food and Drug Administration issue has 70, kind surplus the Chinese medicine dripping pills that wherein is used for cardiovascular system has 20.In addition, it is some in addition to develop the similar drop pill of neutralization application Chinese patent.
Traditional Chinese Medicine Dropping Pill is subject to people's attention just day by day, has now become the emphasis of Chinese medicine preparation research.Traditional Chinese Medicine Dropping Pill is compared with " pill, powder, extract and pellet " administering mode of Chinese medicine, exists the difference of essence.It has adopted Western medicine advanced person's preparation means, drop pill with the solid dispersion technology preparation is that a kind of Chinese medicine preparation fully contacts with mucomembranous surface, middle pharmaceutically active ingredient absorbs, directly advances the Chinese patent medicine preparation dosage form of the administering mode of people's blood circulation by mucosa upper surface cell, its outstanding characteristics enter blood circulation as directly absorbing without liver, avoid first pass effect effectively, it is rapid to have curative effect, bioavailability height, side effect are little, medication characteristics sublingual administration easily, absorb better, onset is faster.Particularly effective ingredient mainly is fat-soluble big, and the material that polarity is little is made containing of drop pill, is easy to enter blood circulation, passes through blood brain barrier.By the through sick institute of the characteristic of medical material " on reach the sea of blood ", onset is rapider, has avoided the Chinese medicine bioavailability low fully, takes inconvenience, the shortcoming that onset is slow, the advantage that the safety that continues to have developed Chinese medicine simultaneously is good, side effect is little, not only taken stopgap measures but also effected a permanent cure.In addition, why Chinese medicine dripping pills is subjected to people's favor, also because it has the many advantages that can't compare with other oral formulations.Compare with tablet, it is little, rapid-action to have a volume, is convenient to advantages such as first aid.The weight of each drop pill is also very light, suits more to carry, and drop pill contacts with saliva after containing in the inlet, i.e. disintegrate rapidly, and by oral cavity and pharyngeal mucosa absorption, so but ante cibum or equal after meal buccal.Therefore, Chinese medicine dripping pills is a kind of form of Chinese drug that is worthy to be popularized, and is a kind of need not having an injection and the dosage form of quick acting, has changed the slow traditional view of Chinese medicine onset that people hold.
Subing drop pills be the seventies in last century Shanghai herbal pharmaceutical one factory take the lead in developing the new medicine preparation that forms at home, it is the Chinese patent medicine that forms through the science screening on the prescription basis of Chinese medicine Styrax Pilulae, its prescription is made up of Styrax and Borneolum Syntheticum two flavor medicines, has causing resuscitation with aromatic drugs, regulating QI to relieve pain is used for angina pectoris, uncomfortable in chest, myocardial infarction etc.Operative norm records in the 15th the 90th page in Ministry of Health of the People's Republic of China's Chinese traditional patent formulation preparation, standard numbering: WS3-B-2899-98.Continue to use on one of this dropping pill formulation quality control project-dissolve scattered time limit (or claim disintegrate) mensuration always be similar to tablet disintegration add plate washer hanging basket method.
Country significantly improved the dropping pill formulation prescription in 05 year, since then, Zhong Guo dropping pill formulation has reached unanimity on " form and content " in a sense, the characteristics that are solid dispersed formulation in the specification requirement of dropping pill formulation quality control and the galenic pharmacy adapt, and become to have the novel solid preparation that is different from general solid preparation, has high bioavailability.
From version " Chinese pharmacopoeia in 2005, dropping pill formulation dissolve scattered time limit mensuration has been made new regulation, requirement does not add plate washer when measuring, and former prescription Subing drop pills (50mg/ grain) is under the condition that does not add baffle plate, the dissolve scattered time limit that its hanging basket method is measured can only be at 50-120 minute, reach far away after 05 year version " specification requirement (within 30 minutes) of Chinese pharmacopoeia regulation, the instant diffusing time limit measure be difficult to qualified.In order to make Subing drop pills can reach new pharmacopeia requirement, be necessary it is carried out research of technique and transformation.
Yet, the Subing drop pills Technical Transformation Study seldom, the domestic Chinese invention patent that the intelligent grade of Rhyme has applied for being entitled as " new type Subing drop pills and preparation method " (application number 200510013496.7) of opening that University Of Tianjin is only arranged, and obtain the authorization in July, 2009.This patent is earlier medicinal ingredient to be made solid dispersion medicine carrying microcapsule, microsphere or the microgranule that particle diameter is 1～100um, be mixed with into drop pill with adjuvant again, though it is realized and has reached Subing drop pills as the solid dispersed formulation technical level, but its preparation process is significantly more complex than simple drop pill production technology, and the technology cost has significantly raising certainly.More worth discussion be that above-mentioned patent is not the microcapsule to prepare, microsphere or microgranule are raw material, further make tablet or capsule, become high bioavailability pharmaceutical preparation, behind the drop pill medium that has melted, carry out the drop pill preparation but dissolve in once more, wouldn't this be reduced into simple dropping pill formulation again? what further be worth discussion is, so-called microcapsule in this drop pill, whether microsphere or microgranule can also exist or bring into play its due efficient effect in other solid preparation, this is still leaving bigger discussion space, at least in this granted patent description, there is not experimental data can confirm so-called microcapsule, microsphere or microgranule also effectively exist in the drop pill medium or are bringing into play its " positive " effect.
Summary of the invention
Main purpose of the present invention is exactly not reach 05 year version " Chinese pharmacopoeia is to the problem of the specification requirement of dropping pill formulation at the former Subing drop pills caused dissolve scattered time limit of writing out a prescription, it is carried out research of technique and transformation, reach the effect of going back the advantageous characteristic that drop pill should have as modern solid dispersed formulation.
The present invention has determined the production technology that improved Subing drop pills is preferable on taking into full account each prescription and the basis of process conditions to the influence in the dropping pill formulation forming process.In Subing drop pills new recipe screening test, do not change the ratio of material medicine in the prescription in principle, only on the substrate adjuvant, have an operation, promptly on the adjuvant basis of regulation proportional quantities, filter out the prescription that can meet existing drop pill quality standard.
The present invention at first discloses a kind of Subing drop pills, comprises medicinal ingredient and adjuvant, and wherein, based on the gross mass of adjuvant, its adjuvant comprises the composition of following mass percent:
Polyethylene Glycol 57%-86%, preferred 64%-79%
Polyoxyethylene stearate (40) ester 14%-43%, preferred 21%-36%.
In order to make Subing drop pills can reach new officinal requirement, the inventor is through discovering in a large number, for Subing drop pills, though the use of the adjuvant of most of conventional auxiliary disintegrate can be shortened its dissolve scattered time limit or disintegration time slightly, but, make the Subing drop pills disintegration time meet 30 minutes requirement of new pharmacopeia, certain distance is still arranged, it is the high-end new non-ionic surfactants that adds the recommended amounts scope, as: pool Luo Shamu, its effect does not very manifest yet, and the inventor attempts to break through the constraint of recommended amounts notion, further improves pool Luo Shamu and adds than row, the drop pill medicinal liquid viscosity that found that this moment heightens, make the drop pill preparation process become difficult, the drop pill molding is not good, and the dissolve scattered time limit of drop pill does not still have substantive breakthroughs.Key of the present invention has been to select the combination of Polyethylene Glycol and polyoxyethylene stearate (40) ester as drop pill substrate and specific supplementary product kind, it can solve aforementioned contradiction well, and can produce beyond thought effect: the medicinal liquid good fluidity under the keeping warm mode, the dissolve scattered time limit of drop pill can shorten nearly 10 times, the drop pill of 50mg weight the soonest can be molten fully diffusing in 10 minutes, thereby guarantee that the dropping pill formulation for preparing meets new officinal all requirements and (comprises roundness, the ball method of double differences is different, dissolve scattered time limit or title disintegrate and assay etc.), prescription based on this, can realize the advantageous characteristic that Subing drop pills has as modern solid dispersed formulation, it is better that drop pill is absorbed, and onset is faster.
The preferred Macrogol 4000 of described Polyethylene Glycol or 6000 or 10000 can use a kind of or its two kinds of combinations wherein, or its three kinds of combinations.
Certainly, the adjuvant that can also comprise a small amount of other auxiliary disintegrate in the described adjuvant of the present invention, mainly comprise one or more the combination among disintegrating agent and non-ionic surface active agent such as carboxymethyl starch sodium, fatty acid Pyrusussuriensis smooth (span is as span 40, sorbester p17) and the pool Luo Shamu (Poloxamer).For those skilled in the art person, disclose in the present invention on the basis of " use of polyoxyethylene stearate (40) ester can successfully prepare and meet the Subing drop pills that new pharmacopeia requires " such fact, disintegration time and medicinal liquid viscosity not being produced under the prerequisite of essence influence, adopt the alternate scheme of other auxiliary disintegrate adjuvant to expect easily the small part that adds polyoxyethylene stearate (40) ester wherein.Generally speaking, the addition of the adjuvant of other auxiliary disintegrate is advisable with 50% of the quality that is no more than polyoxyethylene stearate (40) ester.
Disclosed Subing drop pills accessory formula is suitable for improving the Subing drop pills of various existing prescriptions.
Generally speaking, based on the gross mass of Subing drop pills, Subing drop pills comprises following component by mass percent:
Medicinal ingredient 20%-40%
Adjuvant 60%-80%;
Wherein, based on the gross mass of medicinal ingredient, the mass percent of described medicinal ingredient is composed as follows:
Styrax (also claiming Storax oil) 30%-50%
Borneolum Syntheticum 50%-70%;
The present invention also further discloses the preparation method of above-mentioned Subing drop pills, comprises the following steps:
1) medicinal ingredient styrax and Borneolum Syntheticum added in the Polyethylene Glycol and other specific auxiliary material liquid that has melted in advance, stir, messenger drug fully dissolves with composition under the keeping warm mode, obtains even, the transparent drop pill medicinal liquid of color and luster;
2) then with medicinal liquid under certain heat-retaining condition, splash in the cold oil tubulation with uniform temperature gradient control rate, collect the molding drop pill, centrifugal removal cold oil, collection drop pill.
The present invention is by further optimizing the preparation technology of Subing drop pills, the following molding technological condition and the parameter that can ensure Subing drop pills preparation quality excellence disclosed, as requirements such as medicinal liquid holding temperature, liquid droping speed, cooling oil surface temperature, cold oil bottom temp and cold oil kinematic viscositys.According to condition and the requirement of optimizing process stipulation, can prepare that quality is even, roundness is good, the heavy deviation of ball Subing drop pills little, good quality.
Further optimize step 2) in, described holding temperature is controlled between 60-80 ℃ preferred 65-80 ℃, liquid droping speed be controlled at 30-60 drip/every water dropper/minute, preferred 30-45 drips/every water dropper/minute.
Further optimize step 2) in, in the cold oil tubulation cooling oil surface temperature between 30-50 ℃, preferred 35-50 ℃, the cold oil bottom temp between 0-10 ℃, preferred 3-8 ℃.Described cold oil is selected from crude vegetal (as olive oil), paraffin oil and synthetic dimethyl-silicon wet goods.When wherein using dimethicone, its kinematic viscosity should be at 60-300mm
2Between/the s (centistoke).
Beneficial effect of the present invention:
The present invention writes out a prescription based on former Subing drop pills, break through former Subing drop pills and failed to embody the technology barrier of solid dispersed formulation basic feature, add by simple specific adjuvant, realized that this drop pill is as advantageous characteristic that modern solid dispersion had, and its most key technical specification dissolve scattered time limit can be controlled in 12 to 20 minutes, can realize the optimization of Subing drop pills bioavailability very simply, its ways and means is more economical and practical more than above-mentioned granted patent.
The specific embodiment
Further set forth the present invention below in conjunction with embodiment.Should be understood that these embodiment only are used to illustrate the present invention, but not limit the scope of the invention.The reagent of the experimental technique of unreceipted actual conditions and undeclared prescription is according to normal condition as " condition of the condition described in the Chinese pharmacopoeia version in 2010 or manufacturer's suggestion is carried out or disposed in the following example.
Dissolve scattered time limit detection method: referring to " Chinese pharmacopoeia version appendix in 2010 I K and XII A.
Content assaying method: the photograph gas chromatography (" Chinese pharmacopoeia version appendix in 2010 VI E).
The system suitability test: with poly-ethanol glutarate is immobile phase, and coating concentration is 2.5%; Column temperature is 85 ± 10 ℃, and number of theoretical plate presses Borneolum Syntheticum and the isoborneol peak calculates, and should be not less than 1500.
The preparation of reference substance solution: get the about 100mg of Borneolum Syntheticum reference substance, the accurate title, decide, and puts in the 25ml measuring bottle, adds the ethyl acetate jolting and make dissolving and be diluted to scale, shakes up.
The preparation of need testing solution: get 10 of this product (being equivalent to Borneolum Syntheticum 100mg approximately), the accurate title, decide, and puts in the 25ml measuring bottle, adds the ethyl acetate jolting and make dissolving, and be diluted to scale, shakes up.
Algoscopy: precision is measured reference substance solution and each 1～2 μ l injection gas chromatography of need testing solution respectively, measures, and calculates, promptly.
Embodiment 1 contains the Subing drop pills preparation of polyoxyethylene stearate (40) ester
Taking polyethylene glycol 6000 0.5kg, polyoxyethylene stearate (40) ester 0.2kg, heating makes thawing together, add styrax 0.1kg and Borneolum Syntheticum 0.2kg then, under stirring, dissolve, mixing, and insulation is opened the dropping-pill machine head at 70 ℃, 45 droplets/minute of speed are dripped in control, and splashing into refrigerative, kinematic viscosity is housed is 100 centistoke (mm
2In/s) the dimethicone colonnade, 35 ℃ of cooling oil surface temperatures, 3 ℃ of bottom temps.Collect drop pill, remove the top layer cold oil, can get finished product drop pill 0.9kg, yield 90%, ball focus between the 45-55mg, the heavy 50mg of average ball, and dissolve scattered time limit 12 minutes, content are 98% of Borneolum Syntheticum labelled amount.
The influence that embodiment 2-5 adjunct ingredient proportioning changes
Taking polyethylene glycol 4000 0.6kg, polyoxyethylene stearate (40) ester 0.1kg, heating makes thawing together, add styrax 0.1kg and Borneolum Syntheticum 0.2kg then, under stirring, dissolve, mixing, and insulation is opened the dropping-pill machine head at 70 ℃, 45 droplets/minute of speed are dripped in control, and splashing into refrigerative, kinematic viscosity is housed is 100 centistoke (mm
2In/s) the dimethicone colonnade, 35 ℃ of cooling oil surface temperatures, 3 ℃ of bottom temps.Collect drop pill, remove the top layer cold oil, can get finished product drop pill 0.85kg, yield 85%, ball focus between the 45-55mg, the heavy 50mg of average ball, and dissolve scattered time limit 16 minutes, content are 98% of Borneolum Syntheticum labelled amount.
Taking polyethylene glycol 10000 0.55kg, polyoxyethylene stearate (40) ester 0.15kg, heating makes thawing together, add styrax 0.1kg and Borneolum Syntheticum 0.2kg then, under stirring, dissolve, mixing, and insulation is opened the dropping-pill machine head at 70 ℃, 45 droplets/minute of speed are dripped in control, and splashing into refrigerative, kinematic viscosity is housed is 100 centistoke (mm
2In/s) the dimethicone colonnade, 35 ℃ of cooling oil surface temperatures, 3 ℃ of bottom temps.Collect drop pill, remove the top layer cold oil, can get finished product drop pill 0.83kg, yield 83%, ball focus between the 45-55mg, the heavy 50mg of average ball, and dissolve scattered time limit 14 minutes, content are 97% of Borneolum Syntheticum labelled amount.
Taking polyethylene glycol 6000 0.5kg, polyoxyethylene stearate (40) ester 0.2kg, heating makes thawing together, add styrax 0.1kg and Borneolum Syntheticum 0.2kg then, under stirring, dissolve, mixing, and insulation is opened the dropping-pill machine head at 70 ℃, 45 droplets/minute of speed are dripped in control, and splashing into refrigerative, kinematic viscosity is housed is 200 centistoke (mm
2In/s) the dimethicone colonnade, 35 ℃ of cooling oil surface temperatures, 3 ℃ of bottom temps.Collect drop pill, remove the top layer cold oil, can get finished product drop pill 0.9kg, yield 90%, ball focus between the 45-55mg, the heavy 50mg of average ball, and dissolve scattered time limit 12 minutes, content are 98% of Borneolum Syntheticum labelled amount.
Taking polyethylene glycol 6000 0.4kg, polyoxyethylene stearate (40) ester 0.3kg, heating makes thawing together, add styrax 0.1kg and Borneolum Syntheticum 0.2kg then, under stirring, dissolve, mixing, and insulation is opened the dropping-pill machine head at 70 ℃, 45 droplets/minute of speed are dripped in control, and splashing into refrigerative, kinematic viscosity is housed is 200 centistoke (mm
2In/s) the dimethicone colonnade, 35 ℃ of cooling oil surface temperatures, 3 ℃ of bottom temps.Collect drop pill, remove the top layer cold oil, can get drop pill 0.85kg, yield 90%, ball focus between the 45-55mg, the heavy 50mg of average ball, and dissolve scattered time limit 11 minutes, content are 97% of Borneolum Syntheticum labelled amount.
Embodiment 6 medicinal ingredient proportionings change the influence to the dissolving time limit
Except that medicinal ingredient composition proportioning changes, all the other components and preparation method are identical with embodiment 1: taking polyethylene glycol 60000.5kg, polyoxyethylene stearate (40) ester 0.2kg, heating makes thawing together, add styrax 0.15kg and Borneolum Syntheticum 0.15kg then, under stirring, dissolve mixing, and insulation is at 70 ℃, open the dropping-pill machine head, 45 droplets/minute of speed are dripped in control, and splashing into refrigerative, kinematic viscosity is housed is 100 centistoke (mm
2In/s) the dimethicone colonnade, 35 ℃ of cooling oil surface temperatures, 3 ℃ of bottom temps.Collect drop pill, remove the top layer cold oil, can get finished product drop pill 0.85kg, yield 85%, ball focus between the 45-55mg, the heavy 50mg of average ball, and dissolve scattered time limit 11 minutes, content are 98% of Borneolum Syntheticum labelled amount.
This example explanation when the medicinal ingredient proportioning changes within the specific limits, still can be satisfied new officinal requirement.
Embodiment 7-8 medicinal ingredient toatl proportion changes the influence to the dissolving time limit
Except that the medicinal ingredient ratio changes, all the other components and preparation method are identical with embodiment 1: taking polyethylene glycol 60000.5kg, polyoxyethylene stearate (40) ester 0.2kg, heating makes thawing together, add styrax 0.15kg and Borneolum Syntheticum 0.3kg then, under stirring, dissolve mixing, and insulation is at 70 ℃, open the dropping-pill machine head, 45 droplets/minute of speed are dripped in control, and splashing into refrigerative, kinematic viscosity is housed is 100 centistoke (mm
2In/s) the dimethicone colonnade, 35 ℃ of cooling oil surface temperatures, 3 ℃ of bottom temps.Collect drop pill, remove the top layer cold oil, can get finished product drop pill 1kg, yield 87%, ball focus between the 45-55mg, the heavy 50mg of average ball, and dissolve scattered time limit 22 minutes, content are 98% of Borneolum Syntheticum labelled amount.
Except that the medicinal ingredient ratio changes, all the other components and preparation method are identical with embodiment 1: taking polyethylene glycol 60000.5kg, polyoxyethylene stearate (40) ester 0.2kg, heating makes thawing together, add styrax 0.06kg and Borneolum Syntheticum 0.12kg then, under stirring, dissolve mixing, and insulation is at 70 ℃, open the dropping-pill machine head, 45 droplets/minute of speed are dripped in control, and splashing into refrigerative, kinematic viscosity is housed is 60 centistoke (mm
2In/s) the dimethicone colonnade, 35 ℃ of cooling oil surface temperatures, 3 ℃ of bottom temps.Collect drop pill, remove the top layer cold oil, can get finished product drop pill 0.75kg, yield 85%, ball focus between the 45-55mg, the heavy 50mg of average ball, and dissolve scattered time limit 10 minutes, content are 98% of Borneolum Syntheticum labelled amount.
This two Comparative Examples explanation when the toatl proportion of medicinal ingredient changes within the specific limits, still can be satisfied new officinal requirement.
Embodiment 9-10
Taking polyethylene glycol 6000 0.5kg, polyoxyethylene stearate (40) ester 0.12kg, pool Luo Shamu 188 0.08kg, heating makes thawing together, add styrax 0.1kg and Borneolum Syntheticum 0.2kg then, under stirring, dissolve, mixing, and insulation is opened the dropping-pill machine head at 70 ℃, 45 droplets/minute of speed are dripped in control, and splashing into refrigerative, kinematic viscosity is housed is 100 centistoke (mm
2In/s) the dimethicone colonnade, 35 ℃ of cooling oil surface temperatures, 3 ℃ of bottom temps.Collect drop pill, remove the top layer cold oil, can get drop pill 0.8kg, yield 80%, ball focus between the 45-55mg, the heavy 50mg of average ball, and dissolve scattered time limit 13 minutes, content are 97% of Borneolum Syntheticum labelled amount.
Taking polyethylene glycol 6000 1kg, pool Luo Shamu 188 0.2kg and polyoxyethylene stearate (40) ester 0.2kg, heating makes thawing together, add styrax 0.2kg and Borneolum Syntheticum 0.4kg then, under stirring, dissolve mixing, and insulation is at 75 ℃, open the dropping-pill machine head, 35 droplets/minute of speed are dripped in control, splash into and are equipped with in the refrigerative paraffin oil colonnade, 40 ℃ of cooling oil surface temperatures, 8 ℃ of bottom temps.Collect drop pill, remove the top layer cold oil, can get drop pill 1.7kg, yield 85%, ball focus between the 45-55mg, the heavy 50mg of average ball, and dissolve scattered time limit 16 minutes, content are 97% of Borneolum Syntheticum labelled amount.
The explanation of above-mentioned example adopts other adjuvant that helps disintegrate to substitute polyoxyethylene stearate (40) ester of small part, also can play similar effects.
Embodiment 11-15
Adopt the prescription of embodiment 1, preparation method is made as 60 ℃ and 80 ℃ respectively with the different holding temperatures that are of embodiment 1, the dissolve scattered time limit of product is 12 minutes, and can satisfy new officinal each side requirement, but the drop pill of the former process conditions, its roundness then is higher than the latter not as the latter, content.Test shows that holding temperature can exert an influence to drop pill roundness and content of bornyl alcohol.
Adopt the prescription of embodiment 1, preparation method is made as 30 droplets/minute and 60 droplets/minute respectively with the different speed that are of embodiment 1, the dissolve scattered time limit of product is 12 minutes, and can satisfy new officinal each side requirement, but the former process conditions fail to give full play to medical instruments efficient, and latter's preparation efficiency height, yet when splashing into the excessive cold oil of viscosity, then make easily to produce adhesion between drop pill, test shows that dripping speed can exert an influence to preparation efficiency and drop pill self adhesion.
Adopt the prescription of embodiment 1, preparation method is made as 30 ℃ and 50 ℃ respectively with the different cooling oil surface temperatures that are of embodiment 1, the dissolve scattered time limit of product is 12 minutes, and can satisfy new officinal each side requirement, the former process conditions, its drop pill fineness, roundness are not as the latter, however latter's power consumption.Test shows that cooling oil surface temperature meeting drop pill fineness, roundness and medical instruments energy consumption exert an influence.
Adopt the prescription of embodiment 1, preparation method is made as 0 ℃ and 10 ℃ respectively with the different cold oil bottom temps that are of embodiment 1, the dissolve scattered time limit of product is 12 minutes, and can satisfy new officinal each side requirement, the former process conditions, its drop pill solidifies fastness and is better than the latter, yet consumes energy than the latter.Test shows, the cold oil bottom temp can solidify fastness and energy consumption exerts an influence to drop pill.
Adopt the prescription of embodiment 1, preparation method adopts olive oil and paraffin oil respectively with the different cold oils that are of embodiment 1, the dissolve scattered time limit of product was about in the of 12 minutes, and can satisfy new officinal each side requirement, test shows that cold oil is not obvious to the direct influence that the drop pill quality produces.
Comparative Examples 1 original formulation Subing drop pills
Taking polyethylene glycol 6000 0.7kg, heating makes thawing, adds styrax 0.1kg and Borneolum Syntheticum 0.2kg then, under stirring, dissolve, mixing, and insulation is at 70 ℃, open the dropping-pill machine head, 45 droplets/minute of speed are dripped in control, and splashing into refrigerative, kinematic viscosity is housed is 100 centistoke (mm
2In/s) the dimethicone colonnade, 35 ℃ of cooling oil surface temperatures, 3 ℃ of bottom temps.Collect drop pill, remove the top layer cold oil, can get finished product drop pill 0.9kg, yield 90%, ball focus between the 45-55mg, the heavy 50mg of average ball, and dissolve scattered time limit 120 minutes, content are 95% of Borneolum Syntheticum labelled amount.
Comparative Examples 2 contains the Subing drop pills preparation of carboxymethyl starch sodium and pool Luo Shamu
Taking polyethylene glycol 4000 1kg and pool Luo Shamu 188 0.3kg, heating makes thawing together, add 0.1kg carboxymethyl starch sodium, 0.2kg styrax and 0.4kg Borneolum Syntheticum then, under stirring, dissolve mixing, and insulation is at 65 ℃, open the dropping-pill machine head, 40 droplets/minute of speed are dripped in control, splash into and are equipped with in the refrigerative olive oil colonnade, 35 ℃ of cooling oil surface temperatures, 5 ℃ of bottom temps.Collect drop pill, remove the top layer cold oil, can get drop pill 1.6kg, yield 80%, ball focus between the 45-55mg, the heavy 50mg of average ball, and dissolve scattered time limit 50 minutes, content are 96% of Borneolum Syntheticum labelled amount.。
Comparative Examples 3 contains the Subing drop pills preparation of sorbester p17 and pool Luo Shamu
Taking polyethylene glycol 10000 1.5kg, pool Luo Shamu 188 0.45kg, heating makes thawing together, add sorbester p17 0.15kg, styrax 0.3kg and Borneolum Syntheticum 0.6kg then, under stirring, dissolve, mixing, and insulation is opened the dropping-pill machine head at 70 ℃, 30 droplets/minute of speed are dripped in control, and splashing into refrigerative, kinematic viscosity is housed is 120 centistokes (cst mm
2In/s) the dimethicone colonnade, 45 ℃ of cooling oil surface temperatures, 5 ℃ of bottom temps.Collect drop pill, remove the top layer cold oil, can get drop pill 2.3kg, the heavy 50mg of average ball, dissolve scattered time limit 40 minutes, content are 94% of Borneolum Syntheticum labelled amount.
Comparative Examples 4 contains the Subing drop pills preparation of mooring Luo Shamu
Taking polyethylene glycol 6000 2.75kg and pool Luo Shamu 188 0.75kg, heating makes thawing together, add styrax 0.5kg and Borneolum Syntheticum 1kg then, under stirring, dissolve, mixing, and insulation is opened the dropping-pill machine head at 80 ℃, 30 droplets/minute of speed are dripped in control, and splashing into refrigerative, kinematic viscosity is housed is 200 centistoke (mm
2In/s) the dimethicone colonnade, 50 ℃ of cooling oil surface temperatures, 8 ℃ of bottom temps.Collect drop pill, remove the top layer cold oil, can get drop pill 5kg, the heavy 50mg of average ball, dissolve scattered time limit 50 minutes, content are 95% of Borneolum Syntheticum labelled amount.
Claims (10)
1. a Subing drop pills comprises medicinal ingredient and adjuvant, and wherein, based on the gross mass of adjuvant, its adjuvant comprises following component by mass percent:
Polyethylene Glycol 57%-86%
Polyoxyethylene stearate (40) ester 14%-43%.
2. Subing drop pills as claimed in claim 1 is characterized in that, described Polyethylene Glycol is selected from Macrogol 4000, polyethylene glycol 6000 and cetomacrogol 1000 0.
3. Subing drop pills as claimed in claim 1 is characterized in that, described adjuvant also comprises carboxymethyl starch sodium, the fatty acid Pyrusussuriensis is smooth and one or more the combination of pool among the Luo Shamu.
4. Subing drop pills as claimed in claim 1 is characterized in that, based on the gross mass of Subing drop pills, Subing drop pills comprises following component by mass percent:
Medicinal ingredient 20%-40%
Adjuvant 60%-80%.
5. Subing drop pills as claimed in claim 4 is characterized in that, based on the gross mass of described medicinal ingredient, the mass percent of described medicinal ingredient is composed as follows:
Styrax 30%-50%
Borneolum Syntheticum 50%-70%.
As claim 1-5 arbitrary as described in the preparation method of Subing drop pills, comprise the following steps:
1) medicinal ingredient styrax and Borneolum Syntheticum added in the Polyethylene Glycol and other specific auxiliary material liquid that has melted in advance, stir, messenger drug fully dissolves with composition under the keeping warm mode, obtains even, the transparent drop pill medicinal liquid of color and luster;
2) then with medicinal liquid under certain heat-retaining condition, splash in the cold oil tubulation with uniform temperature gradient control rate, collect the molding drop pill, centrifugal removal cold oil, collection drop pill.
7. the preparation method of Subing drop pills as claimed in claim 6 is characterized in that step 2) in, described holding temperature is controlled between 60-80 ℃, liquid droping speed be controlled at 30-60 drip/every water dropper/minute.
8. the preparation method of Subing drop pills as claimed in claim 7 is characterized in that step 2) in, the cooling oil surface temperature is between 30-50 ℃ in the cold oil tubulation, and the cold oil bottom temp is between 0-10 ℃.
9. the preparation method of Subing drop pills as claimed in claim 8 is characterized in that, described cold oil is selected from crude vegetal, paraffin oil and dimethicone.
10. the preparation method of Subing drop pills as claimed in claim 9 is characterized in that, the kinematic viscosity of described dimethicone is 60-300mm
2/ s.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010206313.4A CN102293794B (en) | 2010-06-22 | 2010-06-22 | Subing pill preparation and preparation thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201010206313.4A CN102293794B (en) | 2010-06-22 | 2010-06-22 | Subing pill preparation and preparation thereof |
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| CN102293794A true CN102293794A (en) | 2011-12-28 |
| CN102293794B CN102293794B (en) | 2014-04-02 |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1695690A (en) * | 2005-05-13 | 2005-11-16 | 天津大学 | New type Subing drop pills and preparation method |
| CN1709412A (en) * | 2005-06-10 | 2005-12-21 | 北京正大绿洲医药科技有限公司 | Liver-benefiting dropping pill prepared from total neterosides of swertia mileensis, and its preparing method |
-
2010
- 2010-06-22 CN CN201010206313.4A patent/CN102293794B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1695690A (en) * | 2005-05-13 | 2005-11-16 | 天津大学 | New type Subing drop pills and preparation method |
| CN1709412A (en) * | 2005-06-10 | 2005-12-21 | 北京正大绿洲医药科技有限公司 | Liver-benefiting dropping pill prepared from total neterosides of swertia mileensis, and its preparing method |
Non-Patent Citations (1)
| Title |
|---|
| 刘柏年: "苏冰滴丸成型问题的探讨", 《中成药》 * |
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