Summary of the invention
It is bulky to the object of the invention is to solve traditional Herba Menthae decoction pieces, can't realize automatic packaging, preserve more than 3 months, its volatile oil content is difficult to reach the problem of pharmacopeia specified standard, a kind of mint liquidity tablet is provided, and its property of medicine does not change, and meets Chinese medical theory, and steady quality, volume is little, and Hygienic Index is arranged, and the shelf cycle is arranged, pharmacy index and traditional decoction pieces are basically identical, the convenient storage can be realized the mechanical automation fractional pack, and dosage is accurate, production technology meets the large requirement of producing of modernization, is fit to Industry Promotion.
Another object of the present invention is to provide a kind of preparation method of mint liquidity tablet.
The technical solution adopted for the present invention to solve the technical problems is: a kind of mint liquidity tablet, described mint liquidity tablet is take traditional Herba Menthae decoction pieces as raw material, process to get granularity 60~100 purpose Herba Menthae low-temperature powders through pulverize at low temperature, the Herba Menthae low-temperature powder is pressed into first the elementary sheet of diameter 16~25mm, elementary sheet is through pulverizing, sieve, behind the granulate repress make diameter 4~12mm tablet be mint liquidity tablet.
Tradition Herba Menthae decoction pieces is a kind of prepared slices of Chinese crude drugs, the present invention is according to the Manufacture of medicinal slices of TCM actual demand, follow traditional Chinese medicine theory, develop a kind of preparing new-type medical herbs drink tablets (mint liquidity tablet) in conjunction with the modern pharmaceutical technology, to reach reliable and stable, the automatic packaging of About The Quality of Sliced Herbal Medicine, satisfy the requirement of prepared slices of Chinese crude drugs industrialization.
The present invention utilizes the Herba Menthae low-temperature powder first, adopts compressing dry granulation, does not add any adjuvant, is prepared into mint liquidity tablet of the present invention.Be easy to preserve the effumability composition in the Herba Menthae, the sheet type is good, and hardness is moderate, big or small homogeneous, and even density, good fluidity is suitable for quantitative automaticization packing and preservation.Mint liquidity tablet is circular tablet.
Once adopted wet granulation to make mint liquidity tablet (ball blast) in the process of the test of the present invention, qualitative, quantitative by mint liquidity tablet ball blast and Tabules and traditional decoction pieces is relatively learnt: mint liquidity tablet of the present invention more can keep involatile constituent in Oleum menthae and the decocting liquid than the ball blast dosage form, so mint liquidity tablet preparation technology is the dry granulation tabletting.
As preferably, the temperature that pulverize at low temperature is processed is-15~0 ℃.
As preferably, the grain graininess behind the granulate is 18~60 orders.It is moderate to process like this mint liquidity tablet hardness that obtains, even density, and good fluidity is suitable for quantitative automaticization packing and preservation.
As preferably, the ratio of granularity 80 purpose Herba Menthae low-temperature powders is more than 80% in the Herba Menthae low-temperature powder.
A kind of preparation method of mint liquidity tablet, described preparation method step is as follows:
(1) pulverize at low temperature
Traditional Herba Menthae decoction pieces pulverize at low temperature in the superfine comminution at low temperature machine is processed, got granularity 60~100 purpose Herba Menthae low-temperature powders;
Grinding particle size and grinding time are proportional, can regulate grinding particle size by the control grinding time;
(2) dry granulation tabletting
The Herba Menthae low-temperature powder that step (1) obtains is poured in the rotary tablet machine, the pressure of adjusting rotary tablet machine is 20~60N, rotating speed is 10~20r/min, suppress to get the elementary sheet of diameter 16~25mm, then elementary sheet is poured in the swing pulverizer and pulverized, sieve, granulate, get granularity 18~60 purpose granules, again granularity 18~60 purpose granules are poured in the rotary tablet machine, the pressure of adjusting rotary tablet machine is 15~30N, and rotating speed is 30~60r/min, suppresses to such an extent that the tablet of diameter 4~12mm is mint liquidity tablet.
As preferably, the temperature that step (1) pulverize at low temperature is processed is-15~0 ℃.
Herba Menthae is the effumability medical material, and the Ordinary pulverization machine is pulverized Herba Menthae, because the crushing process heat production causes loss of volatile oil; In addition, pulverized particles is inhomogeneous.The superfine comminution at low temperature machine carries temperature control system, the adjustable temperature scope be-30 ℃ to room temperature.As long as prerun is found temperature below 0 ℃, and different temperatures is not obvious to volatile oil and particle size influences, so consider energy-saving and cost-reducingly, we determine that the set temperature scope is-15~0 ℃.
As preferably, the Herba Menthae low-temperature powder that step (1) obtains, wherein the ratio of granularity 80 purpose Herba Menthae low-temperature powders is more than 80%.Granularity 80 purpose Herba Menthae low-temperature powders are in the majority, are beneficial to so follow-up dry granulation tabletting, guarantee product quality.
As preferably, the crushing bin of step (1) superfine comminution at low temperature machine is totally-enclosed.The advantage of processing like this is: reduce the medical material loss, keep the production environment cleaning.
As preferably, control the relative humidity of operating environment in the whole preparation process of mint liquidity tablet less than 65%.The relative humidity of control operation environment is stablized non-hygroscopic less than 65% to guarantee the Herba Menthae low-temperature powder.
The invention has the beneficial effects as follows:
1, utilizes first the Herba Menthae low-temperature powder, adopt compressing dry granulation, do not add any adjuvant, be prepared into mint liquidity tablet of the present invention.Be easy to preserve the effumability composition in the Herba Menthae, the sheet type is good, and hardness is moderate, big or small homogeneous, and even density, good fluidity is suitable for quantitative automaticization packing and preservation.
2, the property of medicine does not change, meet Chinese medical theory, and steady quality, volume is little, Hygienic Index is arranged, the shelf cycle is arranged, and pharmacy index and traditional decoction pieces are basically identical, the convenient storage, can realize the mechanical automation fractional pack, dosage is accurate, and production technology meets the large requirement of producing of modernization, is fit to Industry Promotion.
The specific embodiment
Below by specific embodiment, and by reference to the accompanying drawings, technical scheme of the present invention is described in further detail.
Embodiment 1
(1) pulverize at low temperature
Traditional Herba Menthae decoction pieces pulverize at low temperature in CW-12 superfine comminution at low temperature machine is processed, the crushing bin of superfine comminution at low temperature machine is totally-enclosed, the temperature that pulverize at low temperature is processed is-15 ℃, pulverized first 6 minutes, sieve, to not pulverize 5 minutes by part again, and get granularity 60~100 purpose Herba Menthae low-temperature powders, the ratio of granularity 80 purpose Herba Menthae low-temperature powders is more than 80% in the Herba Menthae low-temperature powder.
(2) dry granulation tabletting
The Herba Menthae low-temperature powder that step (1) obtains is poured in the ZP-7 rotary tablet machine, the punch diameter of rotary tablet machine is 16mm, the pressure of adjusting rotary tablet machine is 20N, rotating speed is 10r/min, suppress to get the elementary sheet of diameter 16mm, then elementary sheet is poured in the swing pulverizer and pulverized, sieve, granulate gets granularity 18~60 purpose granules, granularity 18~60 purpose granules is poured in the rotary tablet machine again, the punch diameter of rotary tablet machine is 4mm, the pressure of adjusting rotary tablet machine is 15N, and rotating speed is 30r/min, suppresses to such an extent that the circular tablet of diameter 4mm is mint liquidity tablet.
The relative humidity of operating environment is less than 65% in the whole preparation process of control mint liquidity tablet.
Embodiment 2
(1) pulverize at low temperature
Traditional Herba Menthae decoction pieces pulverize at low temperature in CW-12 superfine comminution at low temperature machine is processed, the crushing bin of superfine comminution at low temperature machine is totally-enclosed, the temperature that pulverize at low temperature is processed is-10 ℃, pulverized first 7 minutes, sieve, to not pulverize 4 minutes by part again, and get granularity 60~100 purpose Herba Menthae low-temperature powders, the ratio of granularity 80 purpose Herba Menthae low-temperature powders is more than 80% in the Herba Menthae low-temperature powder.
(2) dry granulation tabletting
The Herba Menthae low-temperature powder that step (1) obtains is poured in the ZP-7 rotary tablet machine, the punch diameter of rotary tablet machine is 20mm, the pressure of adjusting rotary tablet machine is 40N, rotating speed is 15r/min, suppress to get the elementary sheet of diameter 20mm, then elementary sheet is poured in the swing pulverizer and pulverized, sieve, granulate gets granularity 18~60 purpose granules, granularity 18~60 purpose granules is poured in the rotary tablet machine again, the punch diameter of rotary tablet machine is 6mm, the pressure of adjusting rotary tablet machine is 20N, and rotating speed is 40r/min, suppresses to such an extent that the circular tablet of diameter 6mm is mint liquidity tablet.
The relative humidity of operating environment is less than 65% in the whole preparation process of control mint liquidity tablet.
Embodiment 3
(1) pulverize at low temperature
Traditional Herba Menthae decoction pieces pulverize at low temperature in CW-12 superfine comminution at low temperature machine is processed, the crushing bin of superfine comminution at low temperature machine is totally-enclosed, the temperature that pulverize at low temperature is processed is 0 ℃, pulverized first 6 minutes, sieve, to not pulverize 5 minutes by part again, and get granularity 60~100 purpose Herba Menthae low-temperature powders, the ratio of granularity 80 purpose Herba Menthae low-temperature powders is more than 80% in the Herba Menthae low-temperature powder.
(2) dry granulation tabletting
The Herba Menthae low-temperature powder that step (1) obtains is poured in the ZP-7 rotary tablet machine, the punch diameter of rotary tablet machine is 25mm, the pressure of adjusting rotary tablet machine is 60N, rotating speed is 20r/min, suppress to get the elementary sheet of diameter 25mm, then elementary sheet is poured in the swing pulverizer and pulverized, sieve, granulate gets granularity 18~60 purpose granules, granularity 18~60 purpose granules is poured in the rotary tablet machine again, the punch diameter of rotary tablet machine is 12mm, the pressure of adjusting rotary tablet machine is 30N, and rotating speed is 60r/min, suppresses to such an extent that the circular tablet of diameter 12mm is mint liquidity tablet.
The relative humidity of operating environment is less than 65% in the whole preparation process of control mint liquidity tablet.
Grinding time can be adjusted according to demand.
The form of tradition Herba Menthae decoction pieces and mint liquidity tablet of the present invention is seen Fig. 1, Fig. 2.
The raw material determination of physical appearance
(1) the Herba Menthae low-temperature powder refers to free inclined-plane and the formed maximum angular of horizontal plane of powder body accumulation horizon angle of repose angle of repose.Angle of repose is less, and frictional force is less, and flowability is better.
The method of measuring angle of repose has two kinds: injection method and discharge method.The present invention adopts injection method to measure the angle of repose of powder and tablet.
H: height, r: radius, θ: angle of repose
The flowability of powder body is larger on weight differential and the normal operating impact of the preparations such as granule, capsule, tablet.Record the angle of repose of Herba Menthae low-temperature powder according to injection method greater than 40 degree, directly compressing dry granulation needs dry granulation, again tabletting.
(2) Herba Menthae low-temperature powder hygroscopicity is put into the accurately weighing of flat weighing botle (about 1.0g) that is dried to constant weight with the Herba Menthae low-temperature powder, then places in the exsiccator of different salt supersaturated solutions, preserves 5 days in 25 ℃ of calorstats.Calculate the moisture absorption percentage rate.The hydroscopicity computing formula is as follows:
Take hydroscopicity as vertical coordinate, relative humidity is the abscissa mapping.Two places make tangent line at curve, and the abscissa of two points of intersection of tangents is the critical relative humidity of Herba Menthae low temperature medicated powder, the results are shown in Figure 3.
As shown in Figure 3, the critical relative humidity of Herba Menthae low-temperature powder is about 65%, shows ambient humidity greater than 65% the time, and its hygroscopic capacity can increase sharply.Therefore it is non-hygroscopic to keep the Herba Menthae low-temperature powder to stablize, and requires the relative humidity in control workshop in preparation process less than 65%.
The finished product evaluation of mint liquidity tablet
Take the tablet of diameter 6mm as example
(1) weight differential is according to 2010 editions one one of Chinese Pharmacopoeia, and appendix ID tablet weight variation method checks that the heavy 0.0745g of average sheet meets tablet weight variation limit ± 7.5%.
(2) friability is got 1g, blows away the powder that comes off with hair-dryer, and precise weighing is put in the friabilator, rotates 100 times.Take out, remove powder with method, precise weighing subtracts weight loss/former weight * 100%, calculates friability.The friability of Herba Menthae dry granulation tabletting is 0.8517%.
(3) leach the time and get and make mint liquidity tablet 10g, add in the boil water and stir, required time when measuring complete decoction made from powder, it is complete to record all in 5min decoction made from powder.
(4) bulk density takes by weighing a certain amount of tablet (m), places the 10mL graduated cylinder, fall from distance 5cm, and continued operation 3 times, the measured quantity cylindrical shell amasss (V), and it is 0.4806g/ml that bulk density (d) is obtained bulk density by formula d=m/V.
The factors influencing of mint liquidity tablet preparation method
With pressure (A), revolution (B), Herba Menthae low-temperature powder granularity (C) is main investigation factor, each factor sets up 3 levels separately, adopts orthogonal table L
9(3
4) arrangement test (table 1).Pressure, revolution, Herba Menthae low-temperature powder granularity done find that each factor level is little to the Herba Menthae Haplocalycis volatile oil content influence when single factor is investigated, thus only take granule yield and angle of repose as evaluation index, integrated survey Herba Menthae dry granulation tablet forming technique.
Table 1 factor level
The result shows, comprehensive granule yield and angle of repose result of the test, so the optimum process that draws the Herba Menthae dry granulation is for being A
2B
1C
2Namely utilize 80 order Herba Menthae low-temperature powders, adjusting tablet machine pressure is 40N, and rotating speed is 10r/min.And pass through demonstration test.
The comparison of mint liquidity tablet and traditional Herba Menthae decoction pieces
(1) microscopic features are differentiated
By the microscopic features of traditional Herba Menthae decoction pieces and two kinds of samples of mint liquidity tablet of the present invention are differentiated that the result shows: all can find out conduit, hesperidin crystal, pore, little glandular hair, nonglandular hair and glandular scale in two kinds of samples of traditional Herba Menthae decoction pieces and mint liquidity tablet of the present invention.Show that traditional Herba Menthae decoction pieces and mint liquidity tablet microscopic features of the present invention are without significant difference.
(2) thin layer chromatography is differentiated
As shown in Figure 4: all can detect Mentholum in traditional Herba Menthae decoction pieces and the mint liquidity tablet of the present invention.Both thin layer chromatographys are differentiated without marked difference.Instrument: REPROSTAR 3 laminagraphy systems (Camag company).
(3) water content, total ash and acid-insoluble ash are measured and are seen Table 2
The measurement result of the moisture of table 23 batch traditional Herba Menthae decoction pieces, mint liquidity tablet of the present invention, total ash, acid-insoluble ash
The decoction pieces kind |
Moisture (%) |
Total ash (%) |
Acid-insoluble ash (%) |
Tradition |
11.0 |
6.39 |
0.33 |
Mint liquidity tablet |
9.50 |
6.12 |
0.21 |
(4) the total quantitative determination of Oleum menthae sees Table 3
The traditional Herba Menthae decoction pieces of table 3 and mint liquidity tablet volatile oil of the present invention and moisture are relatively
|
Tradition Herba Menthae decoction pieces |
Mint liquidity tablet |
Herba Menthae oil mass (%) |
1.10 |
0.95 |
Moisture (%) |
11.0 |
9.5 |
In dry product Herba Menthae oil mass (%) |
1.23 |
1.05 |
Determination of volatile oil: 2010 Chinese Pharmacopoeias appendix XD determination of volatile oil Division A League Matches of French Football method must not be less than 0.40%
Determination of water: an appendix IX of 2010 Chinese Pharmacopoeias H the second method toluene method must not be crossed 13.0% result and show: mint liquidity tablet of the present invention and traditional Herba Menthae decoction pieces Herba Menthae oil mass are more or less the same.
(5) volatile ingredient GC trace analysis
As shown in Figure 5: mint liquidity tablet of the present invention and traditional Herba Menthae decoction pieces volatile ingredient be indifference almost.
(6) composition HPLC trace analysis in the aqua methnae decocting liquid
As shown in Figure 6: mint liquidity tablet of the present invention and traditional Herba Menthae decoction pieces decocting liquid composition be indifference almost.
The estimation of stability of mint liquidity tablet of the present invention
(1) hot test
Get mint liquidity tablet of the present invention, put in the hermetically drying device, under 60 ℃ of conditions, placed 10 days, in sampling in 0,5,10 day, detect according to test item.The results are shown in Table 4-1, the result shows that this product is at high temperature placed, and is with comparison in 0 day, test item generation significant change, stable not to heat.Test with method under 40 ℃ with batch mint liquidity tablet of the present invention.The results are shown in Table 4-2.
Show to place under the 4-160 ℃ of condition 10 days hot test results
Show to place under the 4-240 ℃ of condition 10 days hot test results
The result shows: placed 10 days under 60 ℃ of conditions, Determination of menthol significantly reduces, and illustrates that mint liquidity tablet of the present invention is responsive to heat, places 10 days under 40 ℃ of conditions, and Determination of menthol also has a small amount of minimizing.
(2) high wet test
Get mint liquidity tablet of the present invention and put into the accurately weighing of flat weighing botle that is dried to constant weight, place respectively in the exsiccator of supersaturation sodium chloride solution (25 ℃, RH75% ± 5%) and supersaturation potassium nitrate solution (25 ℃, RH92.5% ± 5%).
Under 25 ℃, RH92.5% ± 5% condition, placed 10 days, detect sampling in 0,5,10 day.Test item should comprise moisture absorption weightening finish etc.If moisture absorption weightening finish is more than 5%, then should time test with method at 25 ℃, RH75% ± 5%; If moisture absorption weightening finish is below 5%, and other investigation projects meet the requirements, and then no longer carry out this test.The results are shown in Table 5-1,5-2.
Show to place under 5-125 ℃, RH92.5% ± 5% condition 10 days high humidity result of the tests
Show to place under 5-225 ℃, RH75% ± 5% condition 10 days high humidity result of the tests
The result shows: placed 10 days under 25 ℃, RH92.5% ± 5% condition, moisture absorption is increased weight up to 27.12%, more than 5%, then time tests with method at 25 ℃, RH75% ± 5%, and moisture absorption is increased weight below 5%, and other investigation projects meet the requirements.
(3) strong illumination test
Getting mint liquidity tablet of the present invention, put and be equipped with in the illumination container that illumination is 4500lx ± 500lx daylight lamp, is to place 10 days under 4500lx ± 500lx condition in illumination, detects sampling in 0,5,10 day.Should note controlling temperature in the test, be consistent with room temperature, and note observing the cosmetic variation of test sample.The results are shown in Table 6.
Place 10 days result of the tests under table 64500lx ± 500lx high light condition
The result shows: mint liquidity tablet of the present invention is under strong illumination, and character and discriminating are all unchanged, and Determination of menthol has a small amount of variation, and visible high light is not very large on mint liquidity tablet impact of the present invention.
(4) accelerated stability test
Get Zhejiang and produce traditional Herba Menthae decoction pieces and mint liquidity tablet of the present invention, plastic bag packaging, because of this product to thermo-responsive, place to place under 30 ± 2 ℃ of intelligent growth cabinets, RH65% ± 5% condition and tested in 3 months, detect 3 months stability experiment data such as following table 7 respectively at sampling in 0,1,2,3 month.
3 months experimental datas of acceleration of the traditional Herba Menthae decoction pieces of table 7 and mint liquidity tablet of the present invention
The result can find out: by the trimestral acceleration experiment of three batches of traditional Herba Menthae decoction pieces and mint liquidity tablet of the present invention, find that mint liquidity tablet of the present invention is every to have no significant change, and the Determination of menthol of traditional Herba Menthae decoction pieces has to descend and accelerates.3 months accelerated test thinks that the stability of mint liquidity tablet of the present invention should be better than traditional Herba Menthae decoction pieces.
Conclusion
Pass through stability test, investigate mint liquidity tablet of the present invention in the lower time dependent rule of medicine characteristic of varying environment condition (such as temperature, humidity, light etc.), show that mint liquidity tablet of the present invention is more stable to light, find that temperature and humidity are larger to the stability influence of mint liquidity tablet of the present invention, for pharmaceutical production, packing, storage, traffic condition determine and the foundation of effect duration provides scientific basis.The effect duration of mint liquidity tablet of the present invention can reach about 2 years.
Above-described embodiment is a kind of better scheme of the present invention, is not that the present invention is done any pro forma restriction, also has other variant and remodeling under the prerequisite that does not exceed the technical scheme that claim puts down in writing.