CN1733272A - Pulean pharmaceutical preparation for treating urinary system diseases and process for preparing the same - Google Patents

Abstract

The invention provides a Chinese medicinal preparation for treating urinary system diseases and its preparing process, wherein the preparation is prepared from root of Fructus Rosae Laevigatae, smilax China root, trifoliata (Thunb.) Koidz., Lygodium japonicum, asiatic centella. The preparation can be made into mini-pills, dispersible tablets, soft capsules and other pharmacologically acceptable dosage forms.

Description

Three gold medal pharmaceutical preparatioies of diseases such as treatment urinary system and preparation method thereof

Technical field: the present invention is a kind of three gold medal pharmaceutical preparatioies for the treatment of diseases such as urinary system and preparation method thereof, belongs to technical field of Chinese medicine.

Technical background: acute and chronic pyelonephritis, urinary tract infection is the able-bodied common disease of numerous people in the world today, bring great misery to the patient, traditional Therapeutic Method mostly is antibiotic or physical therapy, the life-time service antibiotic, can make the patient that drug resistance takes place and easily cause double infection, physical therapy then makes most of patients not adhere to and therapy discontinued for a long time.Prevent and treat purpose in order to reach, a large amount of research has been done by many inventors and medicine enterprise, and the product of some treatments also is provided; As: application number is 03124080, and name is called the application of " a kind of pharmaceutical composition for the treatment of diseases of urinary system and preparation method thereof, purposes ", and SANJIN PIAN, SANJIN JIAONANG, the SANJIN KELI of listing, and these three kinds of products are this type of disease of treatment and develop.But conventional tablet need add some excipient, and through compression forming, and its dissolution, disintegrating property are poor; Capsule is the easy moisture absorption of storage, bonding deliquescing for a long time, influences quality and curative effect, the most important thing is that both bioavailability are not high; The SANJIN KELI dose is big, and need to add a large amount of adjuvants, and that in fact takes the patient treatment disease time generally is not less than 50% with the irrelevant adjuvant material of therapeutical effect; The dosage form kind is abundant advanced inadequately, is suitable for crowd's narrow range, and product bioavailability, medicine stability are undesirable; Be 03124080 according to application number in addition, kind and preparation method that name is called the application of " a kind of pharmaceutical composition for the treatment of diseases of urinary system and preparation method thereof, purposes " to be provided can prepare, provide powder, tablet, capsule, concentrated pill, granule, oral liquid, drop pill, patch and ejection preparation etc., but except that conventional tablet and capsule, other dosage forms process route accurately is not provided, is difficult to implement; In fact the needs in market are many-sided, how satisfying doctor and patient is medical worker's task for the demand of certain pharmaceutical preparation, in addition, this patent application only actually just provides the preparation method of tablet, capsule preparations in its specific embodiment, and for the preparation of other description how to prepare, how to select the sort of adjuvant, consumption what, whether effectively or the like do not provide; What people can't produce according to prior art knows; So in view of such circumstances, seek more, therapeutic effect is desirable, pharmaceutical preparation stable and controllable for quality still is that we are badly in need of the thing that solves at present.

Summary of the invention: the objective of the invention is to: a kind of three gold medal pharmaceutical preparatioies for the treatment of diseases such as urinary system and preparation method thereof are provided; Be used for acute and chronic pyelonephritis, treatment of diseases such as chronic urinary tract infection; The present invention makes Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae acceptable dosage form on the pharmaceuticss such as micropill, dispersible tablet and soft capsule preparation, make the preparation disintegrative that obtains good, the bioavailability height, special their supplementary product consumption is all fewer, is particularly suitable for the old people and the inconvenient patient of the tablet of swallowing takes; The soft capsule preparation that provides in the present invention forms drug blockage in the glue shell, solved medicine and met damp and hot problem of unstable, can also cover adverse drug taste, abnormal smells from the patient, can play the effect that increases stability, improves bioavailability.

The present invention constitutes like this: calculate according to components by weight percent, it is with Radix Rosae Laevigatae 8-10 part, Rhizoma Smilacis Chinensis 4-6 part, YANGKAIKOU 4-6 part, Herba lygodii 1-4 part, Herba Centellae 1-4 part or their extract of corresponding weight portion be made dispersible tablet, effervescent tablet, granule, capsule, soft capsule, microcapsule, micropill, drop pill, injection, comprise: powder injection formulation, lyophilized injectable powder, acceptable dosage form on the pharmaceuticss such as slow releasing preparation, controlled release preparation, gel, soft extract, extractum and membrane.Say accurately: described preparation is dispersible tablet, soft capsule, micropill, granule, capsule, effervescent tablet, drop pill, and used Herba Centellae can substitute with the asiaticoside that the Herba Centellae of given component is extracted; In the practice, we find such substituting equally effectively.

The preparation method of three gold medal pharmaceutical preparatioies of the present invention: with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, 2 hours for the first time, 1 hour for the second time, collecting decoction, filter, survey when filtrate is condensed into 60 ℃ of relative densities and be the clear paste of 1.15-1.20, and then make different preparations respectively.

Dispersible tablet in the preparation of the present invention prepares like this: with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, 2 hours for the first time, 1 hour for the second time, collecting decoction filtered, survey when filtrate is condensed into 60 ℃ of relative densities and be the clear paste of 1.15-1.20, drying is pulverized, and gets extract powder, press extract powder: carboxymethyl starch sodium: modified starch: microcrystalline Cellulose=20: 5: 5: 2 part by weight, with extract powder and carboxymethyl starch sodium, modified starch, the microcrystalline Cellulose mixing that sieves adds suitable quantity of water and makes soft material, granulates, granulate, press extract powder again: the part by weight of magnesium stearate=7: 2, add magnesium stearate, adopt the PY129 rotary tablet machine, pressure is 6～7kg, rotating speed is 25r/min, tabletting, promptly.

Pellet in the preparation of the present invention prepares like this: with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, add 6 times of decoctings for the first time and boiled 2 hours, for the second time add 6 times of decoctings and boiled 1 hour, collecting decoction filters, it is 1.15～1.20 thick paste that filtrate is condensed into 60 ℃ of relative densities, at 60～70 ℃ of vacuum dryings, pulverize, add an amount of starch, with 90% ethanol and soybean oil system soft material, extruding-round as a ball pill, drying is made 1000g, promptly.

Specifically: the pellet in the preparation of the present invention prepares like this: with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, for the first time adding 6 times of decoctings boiled 2 hours, for the second time adding 6 times of decoctings boiled 1 hour, collecting decoction, filter, it is 1.15～1.20 thick paste that filtrate is condensed into 60 ℃ of relative densities, at 60～70 ℃ of vacuum dryings, pulverizes, add an amount of starch, with 90% ethanol and soybean oil system soft material, the soft material that makes micropill mechanism ball, wet feed pushed the 0.8mm sieve aperture, and the wet grain of strip cuts off round as a ball, 50～60 ℃ of drying and mouldings, cross 10 mesh sieves and select ball, drying, envionmental humidity should be controlled at below 54%, make 1000g, promptly.

Soft capsule in the preparation of the present invention prepares like this: with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, add 6 times of water gagings for the first time and decocted 2 hours, add for the second time 6 times of water gagings and decocted 1 hour, collecting decoction filters, it is 1.15～1.20 clear paste that filtrate is condensed into 60 ℃ of relative densities, dry below 80 ℃, dry extract is pulverized, and crosses sieve No. five, add soybean oil, Cera Flava is an amount of, mixing is pressed into 1000 of soft capsules, promptly.

Specifically: the soft capsule in the preparation of the present invention prepares like this: with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, add 6 times of water gagings for the first time and decocted 2 hours, add 6 times of water gagings for the second time and decocted 1 hour, collecting decoction, filter, it is 1.15～1.20 clear paste that filtrate is condensed into 60 ℃ of relative densities, dry below 80 ℃, dry extract is pulverized, cross sieve No. five, by medication amount: substrate amount=1: 1 adds soybean oil, 5% Cera Flava, mixing; The capsule shells prescription is gelatin 100g: glycerol 45g: water 100g; Batchingization adhesive tape part is: weigh batching, in the inputization glue jar, merceration is warming up to 65 ± 5 ℃ gradually after 30 minutes, stirred 5 hours and simultaneously evacuation remove bubble, treat evenly back blowing of sizing material, incapsulate after the filtration in the sizing material bucket of machine; During pelleting the sizing material bucket of insulation and the spice bucket of room temperature are delivered to the capsule machine top, be connected with machine, the debugging pellet press, 65 ℃ of gelatin box temperature controls, mould rotating speed 2.0 is rolled in 45 ℃ of sprinkler body temperature controls, rubber thickness 0.8mm, 18～25 ℃ of indoor temperatures, relative humidity＜40%; In conveyer belt was delivered to rotating cage, rotating cage was blown a cold wind over while rotating through the soft capsule of pellet press extrusion, rotated typing dry about 2 hours; The soft gelatin capsule of cold air drying is contained in clean rustless steel charging tray splendid attire in rotating cage, moves to about 22 ℃ of temperature, and airing is 48 hours in the hothouse of relative humidity below 40%, and constantly stirs, and surveys capsule moisture and is being dry suiting below 10%; Be pressed into 1000 of soft capsules, promptly.

Effervescent tablet in the preparation of the present invention prepares like this: with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, add for the first time 6 times of water gagings and decocted 2 hours, add 6 times of water gagings for the second time and decocted collecting decoction 1 hour, filter, it is 1.15～1.20 clear paste that filtrate is condensed into 60 ℃ of relative densities, and dry below 80 ℃, dry extract is pulverized, add 8% sodium bicarbonate, 8% citric acid, 1% aspartame pulverize separately, with the medicated powder mix homogeneously, granulate drying, tabletting, coating, coating material: internal layer uses PVP to add titanium dioxide, when the outer acrylic resin II that uses, 40 ℃ of sheet bed tempertaures, jet velocity 7.0ml/kgmin, promptly.

Drop pill in the preparation of the present invention prepares like this: with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, adding for the first time 6 times of water gagings decocted 2 hours, add for the second time 6 times of water gagings and decocted 1 hour, collecting decoction filters, it is 1.15～1.20 clear paste that filtrate is condensed into 60 ℃ of relative densities, dry below 80 ℃, get two parts of extract powders, a and polyoxyethylene monostearate S-40 portion of PEG4000, mix homogeneously, fuse in the water-bath, stir evenly, drip and in dimethicone, to become ball, drip apart from 5cm drip footpath 2.5mm/2mm, mix 70 ℃ of ointment temperature, liquid coolant height 70cm promptly gets drop pill.

Granule in the preparation of the present invention prepares like this: with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, add 6 times of water gagings for the first time and decocted 2 hours, add for the second time 6 times of water gagings and decocted 1 hour, collecting decoction filters, it is 1.15～1.20 clear paste that filtrate is condensed into 60 ℃ of relative densities, and it is an amount of to add aspartame 30g and dextrin, mixing, get about 2/3 medicinal liquid drying, make extract powder, get the residue medicinal liquid again and do binding agent, granulate, make 1000g, promptly.

Capsule in the preparation of the present invention prepares like this: with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, adding for the first time 6 times of water gagings decocted 2 hours, adding for the second time 6 times of water gagings decocted 1 hour, collecting decoction filters, and it is 1.15～1.20 clear paste that filtrate is condensed into 60 ℃ of relative densities, dry below 80 ℃, dry extract is broken into fine powder, adds starch and adjusts total amount, mix homogeneously, granulate, 50～60 ℃ of dryings, the granulate that sieves incapsulates, make 1000, promptly.

Among the we, Radix Rosae Laevigatae clearing away heat and eliminating dampness leukorrhagia stopping is a monarch drug, Rhizoma Smilacis Chinensis wind-damp dispelling, diuresis, detumescence poison, and the YANGKAIKOU clearing away heat and cooling blood is adjuvant drug altogether; The Herba lygodii heat-clearing and toxic substances removing, Herba Centellae clearing away heat-damp and promoting diuresis, removing toxic substances and promoting subsidence of swelling are messenger drug, all medicines are harmonious, and play the effect of damp-clearing pain-relieving, heat-clearing and toxic substances removing altogether.Compared with prior art, micropill provided by the invention, dispersible tablet disintegrative are good, and the selection of adjuvant is scientific and reasonable, consumption is few, bioavailability is high, are particularly suitable for, old people and swallow tablet or the inconvenient patient of capsule take; Especially dispersible tablet is met the water dispersion tablet of water disintegrate rapidly, the uniform sticky suspension of formation, preferably resolves the not high problem of effective ingredient bioavailability; Soft capsule provided by the invention forms drug blockage in soft gel coat, solved medicine and met damp and hot problem of unstable, can also cover adverse drug taste, abnormal smells from the patient, can play the effect that increases stability, improves bioavailability.Preparation technology advanced person provided by the invention, simple; But and the little patients life-time service of these preparation untoward reaction provided by the invention.

Preparation of the present invention has good antiinflammatory, improves the curative effect of immunologic function, so also can be used for treating diseases such as lumbago and skelalgia, acute glomerulonephritis of baby, chronic prostatitis, uremia's phase chronic renal insufficiency, trichomonal vaginitis, the nephrotic syndrome.

Key of the present invention is: the applicant has carried out a series of experiments and has selected the supplementary product kind of the preparation technology of pharmaceutical preparation provided by the invention, use and the consumption of adjuvant, mutual ratio or the like; Guarantee its science, reasonable, feasible; The preparation that assurance obtains has effective therapeutic effect, and manufacturing enterprise can directly produce according to the present invention, prepare obvious results pharmaceutical preparation, and no longer needs to carry out new groping, study; In fact its key of technology that changes for dosage form just is the ratio that consumption, the adjuvant of supplementary product kind, adjuvant is mutual and the selection of manufacturing condition; If it is improper to select, or can not prepare effective product, sometimes even health risk, otherwise preparation variety with high costs, do not meet market demands again; Selection of the present invention solves these problems; Simultaneously, provide new kind again, made doctor and patient that more choice be arranged to market.

Experimental example 1: dispersible tablet Study on Forming

Dispersible tablet meet water rapidly disintegrate form the water dispersion tablet of uniform sticky suspension, it is poor to have solved other dosage form disintegratives such as former tablet, stripping is shortcoming slowly, the prepared dispersible tablet of the process conditions that the applicant filters out by experiment is disintegrate fully in the 3min in 19 ℃～21 ℃ water, and suspension ability is good, bioavailability is high, dispersed homogeneous degree.

1. adjuvant screening

Prescription extract powder (part) carboxymethyl starch sodium (part) modified starch (part) microcrystalline Cellulose (part) disintegration time/s

1 20 5 5 2 20

2 20 5 0 2 25

3 20 5 5 0 36

4 20 3 5 0 26

5 20 3 0 2 30

6 20 2 3 2 32

The result shows that best prescription is an extract powder: carboxymethyl starch sodium: modified starch: microcrystalline Cellulose=20: 5: 5: 2.

2. tablet forming technique: with extract powder, adjuvant, the binding agent of certain particle size scope, granulate, with made granule at 55 ℃ of dry certain hours of baking oven, add magnesium stearate (extract powder: magnesium stearate=8: 1) mixing, adopt PY129 rotary tablet machine tabletting.

Pressure (kg) rotating speed (r/min) tensile strength (MPa) disintegration time (s)

3～6 22 1.42 28

6～7 25 1.39 15

7～9 27 1.55 30

9～11 30 1.43 34

The result shows that pressure is 6-7kg, when rotating speed is 25r/min, and the tensile strength minimum, the disintegration time minimum, obtained smooth surface, fineness is good.

Experimental example 2: pellet Study on Forming

1 supplementary product kind and consumption are selected

Wettability test is got two parts of extract powders, a starch that adds, and mixing is put respectively in the flat weighing bottle of having weighed, and accurate the title, decide, and is to measure its hygroscopic capacity under 75.0% condition at 25 ℃ of temperature, relative humidity, the results are shown in Table.

The wettability test result

Sample		Pure extract powder	Extract powder+starch
				The weighing bottle numbering		1	2
Weight of material (g)		0.9974	1.0125
				Inhale blanking time	1h	1.64	1.05
2h	4.78	2.44
			3h		6.77	4.72
4h	8.42	6.11
			6h		10.08	7.80
8h	12.90	9.68
			10h		15.54	11.25

Wet percentage rate (%)	12h	18.38	13.04
				24h	21.87	16.11
	36h	25.04	18.32
				48h	36.36	22.41
	72h	42.69	28.66
				84h	45.84	38.81
	96h	46.10	39.04

It is rationally feasible that we think that employing starch is made adjuvant.

2. the system soft material is got the extractum fine powder and starch, soybean oil and ethanol are made soft material with wet granulation process in right amount, makes it to reach to hold agglomeratingly, and that pinches can loose, standby.Research emphasis concentration of alcohol and soybean oil consumption influence pill, and experimental result sees Table.

Concentration of alcohol is investigated

Tested number	Concentration of alcohol	System soft material situation
			1	95% ethanol	Soft material viscosity is not enough
2	90% ethanol	Soft material is moderate
			3	85% ethanol	Soft material easily bonds

As seen from the above table, it is more suitable to select 90% ethanol to make soft material

The soybean oil consumption is investigated

Tested number	The soybean oil consumption	The pill situation
			1	90% ethanol, 1% soybean oil	Soft material viscosity is not enough, can't pill
2	90% ethanol, 2% soybean oil	Soft material is moderate, suitable pill
			3	90% ethanol, 3% soybean oil	Soft material easily bonds, the pill difficulty

As seen from the above table, selecting on the 90% alcoholic acid basis, selecting for use 2% soybean oil pill satisfactory for result.

3. the soft material that makes of pill is with micropill mechanism ball, and wet feed pushed the 0.8mm sieve aperture, and the wet grain of strip cuts off round as a ball, and 50～60 ℃ of drying and mouldings are crossed 10 mesh sieves and selected ball.

4. affected by environment when critical relative humidity (CRH) is measured the examination packing, especially humidity effect has carried out the micropill critical relative humidity and has measured.Concrete operations are as follows: get 7 parts of micropills respectively, and every part of about 1g, the accurate title, decide, put in the weighing botle, open bottle cap, putting into relative humidity respectively is 22.45%, 33.00%, 42.76%, 57.70%, in 75.28%, 84.26%, 92.48% the environment, in 25 ℃ of incubators, placed 84 hours, take out weighing botle, add a cover the accurate title in back and decide, calculate its moisture absorption percentage rate.The results are shown in Table.

Particulate moisture absorption percentage rate (%) under the different relative humiditys

The saturated salt solution kind	Relative humidity (%)	Moisture absorption percentage rate (%)
			CH 3COOK.1.5H 2O	22.45	6.19
MgCl 2.6H 2O	33.00	9.69
			K 2C0 3.2H 2O	42.76	13.54
NaBr.2H 2O	57.70	22.31
			NaCl	75.28	38.79
KCl	84.26	49.03
			KNO 3	92.48	58.51

To moisture absorption percentage rate (%) mapping, the results are shown in accompanying drawing 1 (abscissa is a relative humidity, and vertical coordinate is the moisture absorption percentage rate) with relative humidity (CRH).Know that by figure its CRH% is about 54%, prompting is when granulation, packing, storage, and envionmental humidity should be controlled at below 54%, to guarantee stability of formulation.

Experimental example 3: soft capsule Study on Forming

1. supplementary product kind and consumption are selected

(1) disperse medium (or claiming substrate) is selected: generally fill the solid extract powder, need to add disperse medium, make suspendible shape (or title " toothpaste-like "), be beneficial to the filling pelleting.The disperse matrix of soft capsule is mainly selected oils such as soybean oil, Oleum Arachidis hypogaeae semen, Oleum Sesami and salad oil for use.At oils substrate breed selection, select soybean oil as main matrix.At fill material and substrate energy mix homogeneously, and under the prerequisite of unobstructed defeated material of energy and pelleting, reduce substrates quantity as far as possible.By test of many times, determine medication amount (g): substrate amount (g)=be advisable at 1: 1, experimental result sees Table.

Substrates quantity is investigated

Medication amount (g): substrate amount (g)	1∶1	1∶2
			Quality of liquid medicine	Viscosity, flowability are all good	Differences in viscosity is mobile big

Medication amount (g) as seen from the above table: substrate amount (g)=quality of liquid medicine was better in 1: 1.

In order to increase the denseness of disperse medium, in soybean oil, add an amount of Cera Flava, heating is melted, and makes itself and Cera Flava mixing,

And the Cera Flava consumption carried out investigating the results are shown in Table.

The Cera Flava consumption is investigated

Cera Flava consumption (%)	3	4	5	6
					Quality of liquid medicine	High speed centrifugation (10000/min) 30min layering	High speed centrifugation (10000/min) 30min layering	30min is not stratified for high speed centrifugation (10000/min)	Medium is too thick. and can not mixing

It is better to add 5% Cera Flava as seen from the above table.

(2) the extractum grinding particle size is investigated: extractum is pulverized, crossed 60 orders, 80 orders, 100 orders, 120 mesh sieves respectively, press extractum: substrate=1: 1 is even through the colloid mill mill, and observation mixing situation the results are shown in Table.

The extractum grinding particle size is investigated

Granularity (order)	60	80	100	120
					The mixing situation	Can not mixing, high speed centrifugation (10000 commentaries on classics/min) 30min layerings	Can mixing, high speed centrifugation (10000 change/min) 30min is not stratified	Can mixing, high speed centrifugation (10000 change/min) 30min is not stratified	Can mixing, high speed centrifugation (10000 change/min) 30min is not stratified

As seen from the above table, extractum was pulverized just energy mixing of 80 mesh sieves, therefore, selected extractum to pulverize 80 mesh sieves (i.e. No. five sieves)

(3) capsule shells prescription screening: by table proportion scale batching, put into the 500ml bottle,suction, 65 ℃ of water-baths are dissolved, automatically stirringization glue, the while evacuation, about vacuum 0.095Mpa, insulation was placed 1 hour after 5 hours, filtered glue, get a part of glue and measure viscosity and other performance, part glue evenly is paved into skim (smear below earlier one deck liquid paraffin) on iron plate, be positioned over to observe the rubber performance next day and judge, the results are shown in Table.

Rubber batching The selection result

Prescription	Viscosity (Mpas)	Flexibility	Elasticity	Toughness	Characteristics	Overall merit
							1. gelatin 100g: glycerol 35g: water 100g	3.66	--	---	+	Crisp, hard	Difference
2. gelatin 100g: glycerol 45g: water 100g	3.35	+	++	+++	Tough, good film-forming property	Fine
							3. gelatin 100g: glycerol 55g: water 100g	3.64	+	++	+	Good springiness	Generally
4. gelatin 100g: glycerol 45g: water 30g	3.83	++	++	+	Good springiness, viscosity is big	Fine
							5. gelatin 100g: glycerol 45g: water 120g	3.06	+++	+	--	Too soft	Difference
6. gelatin 100g: glycerol 35g: sorbic acid 5g: water 100g	3.48	--	+	++	Tough	Better
							7. gelatin 100: glycerol 35g: sorbic acid 10g: water 100g	3.48	+	+	+	The perverse performance of wearing is good	Fine
8. gelatin 100g: glycerol 45g: sorbic acid 5g: water 100g	3.51	++	+	+	Tough	Better
							9. gelatin 100g: glycerol 45g: sorbic acid 10g: water 100g	3.46	++	++	-	Soft	Generally
10. gelatin 100g: glycerol 25g: sorbic acid 10g: water 100g	3.62	+	+	++	Tough	Fine
							11. gelatin 100g: glycerol 35g: sorbic acid 20g: water 90g	3.57	+	++	+	It is good to pierce through performance	Fine
L2. gelatin 100g: glycerol 55g: sorbic acid 5g: water 90g	3.32	++	++	+	0.8mm following rubber is easily broken	Better
							13. gelatin 84g: glycerol 26g: sorbic acid 28g: water 20g	Glue is too thick, can't change glue
L4. gelatin 100g: arabic gum 25g: glycerol 35g: water 100g	3.57	-	---	+	Crisp, face colour band ash	Difference
							15. gelatin 85g: arabic gum 15g: glycerol 45g: water 100g	3.50	-	+	+	Face colour cast ash	Generally
16. gelatin 85g: arabic gum 15g: glycerol 60g: sorbic acid 10g: water 60g	3.47	+	+	++	0.2～0.8mm rubber tearing strength is big	Fine
							17. gelatin 50g: arabic gum 150g: sorbic acid 10g: glycerol 60g: water 55g	3.68	+	+	--	Crisp	Difference
18. gelatin 35g: arabic gum 15g: glycerol 45g: sorbic acid 10g: water 110g	3.52	+	+	+	Face colour cast ash	Generally
							19. gelatin 85g: arabic gum 15g: glycerol 60g: sorbic acid 10g: water 90g	3.39	+	+	+	0.5mm following rubber poor flexibility	Generally
20. gelatin 100g: arabic gum 25g: glycerol 45g: sorbic acid 5g: water 100g	3.36	+	--	+	Crisp, face colour band ash	Generally

Through above screening, overall merit, prescription 2,4,7,11,16 prepared rubber quality are good, consider the characteristics of fill material, select prescription 2, i.e. gelatin 100g: glycerol 45g: water 100g.

2. molding technological condition is investigated

(1) fill material mixes: laboratory is got extractum, adds substrate, uses the vibrating ball-mill mixing, and evacuation removes bubble, and is standby

(2) batchingization glue is investigated: by aforementioned preferred prescription is gelatin: glycerol: water=100g: 45g: the 100g weigh batching with different temperatures glue, the results are shown in Table.

Changing the glue temperature investigates

Temperature (℃)	Change the glue time (H)	The rubber quality
			50	5	Softer
60	5	Good
			70	5	Good
80	5	Harder
			90	5	Rubber has bubble, and is hard

By the table prompting, it is the most suitable with 60～70 ℃ to change the glue temperature.So batchingization adhesive tape part is: weigh batching, in the inputizations glue jar, merceration is warming up to 65 ± 5 ℃ gradually after 30 minutes, stirs 5 hours also the while evacuation except that bubble, treat sizing material even after blowing, incapsulate after the filtration in the sizing material bucket of machine.

(3) pelleting: the sizing material bucket of insulation and the spice bucket of room temperature are delivered to the capsule machine top, be connected the debugging pellet press with machine, 65 ℃ of gelatin box temperature controls, mould rotating speed 2.0 is rolled in 45 ℃ of sprinkler body temperature controls, rubber thickness 0.8mm, 18～25 ℃ of indoor temperatures, relative humidity＜40%.Treat that it is the 400mg/ grain that ball content loading amount is regulated in pellet press debugging back.Survey loading amount once every half an hour in the pelleting process.

(4) drying: the dry soft capsule through pellet press extrusions of typing is in conveyer belt is delivered to rotating cage, and rotating cage is blown a cold wind over while rotating, rotates about 2 hours of the drying of finalizing the design.

Tray dried soft gelatin capsule of cold air drying in rotating cage is contained in clean rustless steel charging tray splendid attire, moves to about 22 ℃ of temperature, and airing is 48 hours in the hothouse of relative humidity below 40%, and constantly stirs, and surveys capsule moisture and is being dry suiting below 10%.

The drying lime light: the dry typing drying of rolling that adopts combined with two steps of tray dried, and the typing of rolling is dry is advisable with two hours through investigation, and overlong time is then rough; Baking temperature is advisable about investigating with 22 ℃, and it is long that it's low drying time is past temperature, though increase in temperature can shorten drying time, easily produces Testudinis to capsule surface and splits; Dry relative humidity should be lower than 40% through investigating, otherwise is difficult for dry; Got final product below 10% with control moisture drying time about 24～48 hours.

(5) essence is chosen: the soft capsule that drying is good is through selecting with the lamp inspection desk of 75% ethanol disinfection, and the outward appearance eligible is packed in the rustless steel charging basket.

(6) clean: will select qualified capsule in rustless steel container, the silk with clean uses 95% an amount of ethanol that its surface clean is clean.

(7) packing: cleaned soft gelatin capsule is packed with aluminium plastic material (blister ocular form).

Experimental example 4 effervescent tablet moulding processs

1. the selection of coating material

Coating material

Group internal layer skin

1 - -

Add the titanium dioxide acrylic resin II number 2 acrylic resin II numbers

3 Radix Acaciae senegalis add the titanium dioxide acrylic resin IV number

4 PVP add the titanium dioxide acrylic resin II number

Add the titanium dioxide acrylic resin IV number 5 acrylic resin IV numbers

Screening experiment

Group disintegration time min outward appearance (0 month) outward appearance (June)

The 1 8.12 smooth moisture absorptions

2 10.32 is smooth

3 8.21 flat film clothing damaged portion labels expose the moisture absorption

4 5.43 is smooth

5 9.11 flat film clothing damaged portion labels expose the moisture absorption

Experimental result as can be known because effervescent tablet is made up of two components of soda acid, there are meta-acid or alkali phenomenon partially in the part, can make acrylic resin be subjected to the influence of soda acid and destroys, institute's internal layer has added PVP and has added titanium dioxide, makes the isolation of acrylic resin and label, acid and alkali alkali destruction.

2. the screening of art for coating.

The art for coating uniform designs table

Experiment sheet bed tempertaure (℃) jet velocity ml/kgmin (s) outward appearance

1 - - -

2 40 7.0 is good

3 40 6.5 bonding dies, pitted skin

4 50 7.0 have mottle

5 50 6.5 fineness are relatively poor

6 60 6.5 Pericarpium Citri Reticulatae, unfilled corner

Experimental result as can be known, coating material: internal layer uses PVP to add titanium dioxide, the outer acrylic resin II that uses, during 40 ℃ of sheet bed tempertaures, jet velocity 7.0ml/kgmin, promptly.

Experimental example 5 drop pill moulding processs

1. the screening of substrate

The fusion situation of substrate and principal agent relatively

The prescription number

Prescription 1

Prescription 2

Prescription 3

Prescription 4

Prescription 5

Prescription 6

Prescription 7

Prescription 8

Medicine (g)	10	10	20	20	20	30	30	30
									Macrogol 4000 (g)	30	20	10	30	20	10
Polyethylene glycol 6000 (g)				20	30	35	40	45
									S-40			10	10			10
The fusion situation of principal agent and substrate	Principal agent can merge with substrate, but system does not have flowability	Principal agent can merge with substrate, and system is better mobile	Principal agent can merge with substrate, and the system flowability is fine	Principal agent can merge with substrate, and the system flowability is fine	Principal agent and substrate merge relatively poor	Principal agent can merge with substrate, but system does not have flowability	Principal agent can merge with substrate, and the system flowability is relatively poor	Principal agent can merge with substrate, and system is better mobile
									The drop pill outward appearance		Roundness is poor, hangover	Smooth, roundness is good	Smooth, roundness is good			Roundness is poor, hangover	Roundness is poor slightly, and hangover is arranged slightly
Drop pill hardness		Hardness is little	Hardness is better	Hardness is better			Hardness is better	Hardness is better
									The ball method of double differences is different		20％	8.0％	8.5％			25％	20％
Dissolve scattered time limit (min)		7～8	4～5	9～10			6～8	6～8

The result shows, the drop pill stripping that composite interstitial substance makes is very fast, because the esterification of polyethylene glycols substrate forms, be the surface-active water-soluble base of a kind of tool (fusing point is 46～51 ℃), S-40 has changed polyethylene glycols itself and has not had close ester structure and surface-active character, improve the dissolubility of insoluble drug, help the absorption of medicine.

2. drip distance, drip selection fast, temperature

Drip distance, drip selection fast, temperature: drip footpath 2.5mm/2mm.Evaluation index: the heavy qualification rate of ball is by mass discrepancy requirement of Pharmacopoeia of the People's Republic of China version in 2000: meet ± 7.5% within.

Group temperature/heavy qualification rate/the % of a ℃ distance/cm liquid coolant height/cm ball

1 80 4 50 79.3

2 80 5 60 87.3

3 80 8 70 82.1

4 70 4 60 91.0

5 70 5 70 95.4

6 70 8 50 90.2

7 60 4 70 91.3

8 60 5 50 90.4

9 60 8 60 86.9

The result shows, the optimum condition of preparation drop pill of the present invention: drip apart from 5cm, drip footpath 2.5mm/2mm mixes 70 ℃ of ointment temperature, liquid coolant height 70cm.

Experimental example 6 granule formation technologies

The applicant finds that it is exactly that hygroscopicity is strong, mouthfeel is bitter that this product is made the greatest problem of granule in development process.Because consider the crowd of being suitable for, draw up and be equipped with sugar-free granule, so supplementary product consumption is just fewer, and this product contains the high medical materials of polyoses content such as Radix Angelicae Sinensis, the former powder hygroscopicity of extractum is very strong, supplementary product consumption can not be too much situation under, strictness screening and control that must be by adjuvant and process conditions just can address these problems.

(1) supplementary product kind and consumption thereof are investigated

1. correctives is selected

The function as sweeteners comparison sheet

Kind	Sucrose	Aspartame	Cyclamate
				Sugariness	1 (standard of comparison)	180～300	50 times
Flavor matter	Good	Good	The metalloid flavor is arranged
				Price	1 (standard of comparison)	80 times	Cost is low
Consumption	Unrestricted (but diabetes are avoided usefulness)	Unrestricted	Consumption is limited, generally is no more than 0.1%
				Safety	Good	Good	Better

Through relatively comprehensive, selected aspartame is made the correctives of this product.

2. wettability test is got two parts of extract powders, a dextrin that adds, and mixing is put respectively in the flat weighing bottle of having weighed, and accurate the title, decide, and is to measure its hygroscopic capacity under 75.0% condition at 25 ℃ of temperature, relative humidity, the results are shown in Table.

The wettability test result

Sample		Pure extract powder	Extract powder+dextrin
				The weighing bottle numbering		1	2
Weight of material (g)		1.0012	0.9984
				Moisture absorption blanking time percentage (%)	1h	1.53	1.17
2h	4.72	2.53
			3h		6.78	4.58
4h	8.31	6.29
			6h		10.11	7.69
8h	12.69	9.73
			10h		15.51	11.32
12h	18.49	13.32
			24h		21.80	16.45
36h	25.21	18.49
			48h		36.67	22.68
72h	42.88	28.74
			84h		45.80	32.51
96h	46.13	32.81

Experimental example 7: bioavailability relatively

With the effective ingredient asiaticoside is index, the SD rat, body weight 250～280g, male and female half and half, fasting overnight (can't help water), next day gastric infusion, dosage is 7.8g/kg.15min before administration and after the administration, 30min, 60min, 90min, 2h, 3h, the blood sampling of 4h and 8h eye socket endocanthion, each blood sample point is with 6 rats.Blood sample is put the anticoagulant heparin pipe, the centrifugal 5min of 3000r/min, and separated plasma is put-10 ° and is saved to analysis.High performance liquid chromatograph is by the M510 pump, the U6K injector, and M490 variable-wavelenght detector and 810 chromatographic data treating stations are formed (Waters, the U.S.).Asiaticoside extracts in the blood plasma: get 0.5mL blood plasma, add protein precipitant, the centrifuging and taking supernatant adds the 5mL n-butyl alcohol, interior mark 50 μ L, and test tube is done 30 ° and is favoured horizontal direction jolting device, 15min is extracted in jolting, centrifugal (3000r/min) 10min, aqueous phase discarded, the accurate 4mL organic facies of drawing is in a clean tube, at 37 ℃ of water-baths, N ₂Dry up under the air-flow, residue dissolves the sample introduction analysis again with 200 μ L mobile phases.

Rat plasma asiaticoside concentration change (N=6)

Time/h blood plasma asiaticoside concentration/(ug-L ^-1)

Dispersible tablet of the present invention micropill of the present invention soft capsule of the present invention granule SANJIN PIAN of the present invention SANJIN JIAONANG

0 - - - - - -

0.25 0.22±0.35 0.26±0.05 0.20±0.32 0.25±0.15 0.17±0.43 0.14±0.18

0.50 1.63±1.24 1.72±0.45 1.52±0.17 1.30±1.35 0.85±0.21 0.95±0.40

1.00 2.32±0.42 2.42±0.40 2.57±0.39 2.30±0.86 1.95±0.54 1.81±0.73

1.50 1.67±0.53 1.73±0.85 1.82±1.25 1.60±0.57 2.25±0.73 2.20±0.63

2.00 1.78±1.26 1.82±1.16 1.83±1.42 1.75±1.09 1.96±1.01 1.83±1.47

3.00 1.28±0.65 1.29±0.37 1.25±1.07 1.30±1.03 1.55±1.25 1.52±1.22

4.00 0.86±0.41 0.82±0.29 0.92±0.63 0.8g±1.22 0.85±3.41 0.93±0.13

6.00 0.47±0.55 0.39±1.13 0.52±0.44 0.50±0.87 0.51±0.32 0.54±0.05

8.00 0.26±0.13 0.25±1.16 0.22±0.40 0.32±1.03 0.29±0.27 0.26±0.11

The result shows, the preparation of the present invention's preparation is that the bioavailability that records of index is good with the asiaticoside, absorbs obviously very fast.

Experimental example 8: antiinflammatory action

The influence of xylol induced mice auricle edema

Experimental technique faces with preceding that tablet, preparation of the present invention are mixed with the 0.30g/ml suspension with 0.5% Carboxymethyl cellulose sodium (CMC-Na) is standby, and animal is used healthy Kunming mouse, body weight 20 grams.Mice is divided into 5 groups (matched group normal saline) at random, irritate the long-pending 20ml/kg of being of body of stomach, two weeks of continuous irrigation stomach, once a day, the last administration was applied to mouse right ear with microsyringe with 0.05ml dimethylbenzene after 30 minutes, put to death mice after 15 minutes, cut two ears along the auricle baseline, dash with the 8mm diameter steel and to lay round auricle in left and right sides auricle same area respectively, torsion balance claims two auricle weight in wet bases, with two auricle weight differences as the swelling level index.Inhibitory rate of intumesce equals the difference of average swelling degree of matched group and the average swelling degree of administration group and takes advantage of 100% again divided by the average swelling degree of matched group.

Average swelling degree (mg) suppression ratio (%) of group dosage (g/kg) animal (only)

Matched group 20ml/kg 8 24.21 ± 4.60

SANJIN PIAN group 6.0 8 16.60 ± 2.10 35.10

Micropill group 6.0 8 14.45 of the present invention ± 4.35 40.19

Dispersible tablet group 6.0 8 14.20 of the present invention ± 3.72 41.15

Soft capsule group 6.0 8 13.12 of the present invention ± 5.35 44.25

The result shows that preparation of the present invention has good antiinflammatory action, and effect is better than the SANJIN PIAN group.

Experimental example 9: to the experimentation of immune function of mice influence

1. the BALBLC mice is got in the influence of mice hemolysis barren spot experiment, body weight 22 ± 2g, random packet, be blank group, model group, SANJIN JIAONANG positive controls, preparation group of the present invention, male and female half and half, the blank group distilled water that deturs talis dosis, SANJIN JIAONANG group, preparation group of the present invention all give 1.5mg/d, all irritate stomach.Every w weighed 1 time in continuous 3 months.5d before the experiment, every mouse subcutaneous injection cyclophosphamide 80mg/kg.Test the same day, mice is put to death, and gets spleen and puts into and fill Hank, in the little plate of S liquid, on the little steel mesh of 200 orders, grind spleen with plunger, filter Hank, S liquid washing 3 times on the nylon wire, each centrifugal 10min, splenocyte is suspended in the cold Hank of 10ml, and in the S liquid, hands bullet mixing is the immunocyte suspension.In test tube, add 107 cells/ml splenocyte suspension 20ul; 15%SRBC50ul; 1: 8 complement 50ul, Hank, S liquid 280ul, mixing sucks 60ul at every turn, injects two cells of preprepared, as underfill, puts into 37 ℃ of incubators, incubation 1.5h with 1%SRBC filling paraffin edge sealing.Microscopically carries out plaque counting, and every two cell plaque sums are the PFC number in the splenocyte.

Each group is to the influence of mice body weight and plaque number (x ± s)

Group drug dose mice (n) body weight (g) plaque number

Behind the medicine prodrug

Matched group NS 10 20.09 ± 1.90 27.60 ± 4.54 37.11 ± 8.38

Model group-10 20.24 ± 2.93 26.35 ± 3.21 17.31 ± 7.20

SANJIN JIAONANG group 1.5mg/d 10 20.50 ± 2.11 28.59 ± 3.65 34.35 ± 8.50

Capsules group 1.5mg/d 10 20.24 of the present invention ± 1.85 27.59 ± 4.42 33.15 ± 8.70

The result shows that mouse stomach is respectively organized the PFC counting with preparation for treating of the present invention and obviously improved after 3 months, and relatively there were significant differences with model group, and be not less than the SANJIN JIAONANG matched group.

2. mice is got in the influence of mice serum immunoglobulin, body weight 22 ± 2g, random packet, i.e. blank group, model group, SANJIN JIAONANG matched group, groups of grains of the present invention, male and female half and half, the blank group distilled water that deturs talis dosis, SANJIN JIAONANG group, groups of grains of the present invention give 1.5mg/d, all irritate stomach, every w weighed 1 time in continuous 3 months.The same day was respectively organized the mice numbering in experiment, and eyeball is got blood, and the centrifuging and taking determination of serum is respectively organized mouse immune albumen.

To the influence of mice serum immunoglobulin (X ± S)

Group drug dose (g/kg) mice IgG (mg/L) IgA (mg/L) IgM (mg/L)

Normal control group NS 12 3.65 ± 0.65 0.36 ± 0.17 0.58 ± 0.22

Model group-10 2.91 ± 0.68 0.30 ± 0.10 0.45 ± 0.27

SANJIN JIAONANG group 15mg/d 10 3.86 ± 1.52 0.81 ± 0.23 0.75 ± 0.04

Groups of grains 1.5mg/d 10 3.88 of the present invention ± 1.07 0.88 ± 0.12 0.84 ± 0.21

The result shows that serum Immunoglobulin IgA, IgA, IgM content improve behind the mouse gavaging preparation of the present invention, and the curative effect of human body immunity improving function is not less than the SANJIN JIAONANG matched group.

Description of drawings: accompanying drawing 1 is the sketch map of moisture absorption percentage rate (%) being done with relative humidity (CRH); Wherein: abscissa is a relative humidity, and vertical coordinate is the moisture absorption percentage rate.

Concrete embodiment: (part: refer to weight portion: as: kilogram, gram etc.)

Embodiments of the invention 1: 8 parts of Radix Rosae Laevigataes, 4 parts of Rhizoma Smilacis Chinensiss, 4 parts of YANGKAIKOU, 1 part of Herba lygodii, 1 part of Herba Centellae, with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, 2 hours for the first time, 1 hour for the second time, collecting decoction filters, and surveys when filtrate is condensed into 60 ℃ of relative densities to be the clear paste of 1.15-1.20, dry, pulverize, get extract powder, press extract powder: carboxymethyl starch sodium: modified starch: microcrystalline Cellulose=20: 5: 5: 2 part by weight, with extract powder and carboxymethyl starch sodium, modified starch, the microcrystalline Cellulose mixing that sieves, add suitable quantity of water and make soft material, granulate granulate, press extract powder again: the part by weight of magnesium stearate=7: 2, add magnesium stearate, adopt the PY129 rotary tablet machine, pressure is 6～7kg, rotating speed is 25r/min, tabletting promptly gets dispersible tablet, this product oral, three times on the one, each 2.

Embodiments of the invention 2: 10 parts of Radix Rosae Laevigataes, 6 parts of Rhizoma Smilacis Chinensiss, 6 parts of YANGKAIKOU, 4 parts of Herba lygodii, 4 parts of Herba Centellaes, with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, for the first time adding 6 times of decoctings boiled 2 hours, for the second time adding 6 times of decoctings boiled 1 hour, collecting decoction, filter, it is 1.15～1.20 thick paste that filtrate is condensed into 60 ℃ of relative densities, at 60～70 ℃ of vacuum dryings, pulverize, add an amount of starch, with 90% ethanol and soybean oil system soft material, push a round as a ball pill, drying, make 1000g, promptly get pellet.

Embodiments of the invention 3: 8 parts of Radix Rosae Laevigataes, 4 parts of Rhizoma Smilacis Chinensiss, 4 parts of YANGKAIKOU, 1 part of Herba lygodii, 1 part of Herba Centellae, with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, for the first time adding 6 times of decoctings boiled 2 hours, for the second time adding 6 times of decoctings boiled 1 hour, collecting decoction filters, and it is 1.15～1.20 thick paste that filtrate is condensed into 60 ℃ of relative densities, at 60～70 ℃ of vacuum dryings, pulverize, add an amount of starch, with 90% ethanol and soybean oil system soft material, the soft material that makes micropill mechanism ball, wet feed pushed the 0.8mm sieve aperture, the wet grain of strip cuts off round as a ball, and 50～60 ℃ of drying and mouldings are crossed 10 mesh sieves and selected ball, dry, envionmental humidity should be controlled at below 54%, makes 1000g, promptly gets pellet.

Embodiments of the invention 4: 10 parts of Radix Rosae Laevigataes, 5 parts of Rhizoma Smilacis Chinensiss, 5 parts of YANGKAIKOU, 3 parts of Herba lygodii, 3 parts of Herba Centellaes, with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, adding for the first time 6 times of water gagings decocted 2 hours, adding for the second time 6 times of water gagings decocted 1 hour, collecting decoction, filter, it is 1.15～1.20 clear paste that filtrate is condensed into 60 ℃ of relative densities, dry below 80 ℃, dry extract is pulverized, cross sieve No. five, add soybean oil, Cera Flava is an amount of, mixing, be pressed into 1000 of soft capsules, promptly get soft capsule.

Embodiments of the invention 5: 8 parts of Radix Rosae Laevigataes, 4 parts of Rhizoma Smilacis Chinensiss, 4 parts of YANGKAIKOU, 1 part of Herba lygodii, 1 part of Herba Centellae, with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, adding for the first time 6 times of water gagings decocted 2 hours, adding for the second time 6 times of water gagings decocted 1 hour, collecting decoction, filter, it is 1.15～1.20 clear paste that filtrate is condensed into 60 ℃ of relative densities, dry below 80 ℃, dry extract is pulverized, cross sieve No. five, press medication amount: substrate amount=1: 1 adding soybean oil, 5% Cera Flava, mixing; The capsule shells prescription is gelatin 100g: glycerol 45g: water 100g; Batchingization adhesive tape part is: weigh batching, in the inputization glue jar, merceration is warming up to 65 ± 5 ℃ gradually after 30 minutes, stirred 5 hours and simultaneously evacuation remove bubble, treat evenly back blowing of sizing material, incapsulate after the filtration in the sizing material bucket of machine; During pelleting the sizing material bucket of insulation and the spice bucket of room temperature are delivered to the capsule machine top, be connected with machine, the debugging pellet press, 65 ℃ of gelatin box temperature controls, mould rotating speed 2.0 is rolled in 45 ℃ of sprinkler body temperature controls, rubber thickness 0.8mm, 18～25 ℃ of indoor temperatures, relative humidity＜40%; In conveyer belt was delivered to rotating cage, rotating cage was blown a cold wind over while rotating through the soft capsule of pellet press extrusion, rotated typing dry about 2 hours; The soft gelatin capsule of cold air drying is contained in clean rustless steel charging tray splendid attire in rotating cage, moves to about 22 ℃ of temperature, and airing is 48 hours in the hothouse of relative humidity below 40%, and constantly stirs, and surveys capsule moisture and is being dry suiting below 10%; Be pressed into 1000 of soft capsules, promptly get soft capsule.

Embodiments of the invention 6: 10 parts of Radix Rosae Laevigataes, 6 parts of Rhizoma Smilacis Chinensiss, 6 parts of YANGKAIKOU, 4 parts of Herba lygodii, 4 parts of Herba Centellaes, with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, add for the first time 6 times of water gagings and decocted 2 hours, add 6 times of water gagings for the second time and decocted collecting decoction 1 hour, filter, it is 1.15～1.20 clear paste that filtrate is condensed into 60 ℃ of relative densities, and dry below 80 ℃, dry extract is pulverized, add 8% sodium bicarbonate, 8% citric acid, 1% aspartame pulverize separately, with the medicated powder mix homogeneously, granulate drying, tabletting, coating, coating material: internal layer uses PVP to add titanium dioxide, when the outer acrylic resin II that uses, 40 ℃ of sheet bed tempertaures, jet velocity 7.0ml/kgmin promptly gets effervescent tablet.

Embodiments of the invention 7: 8 parts of Radix Rosae Laevigataes, 4 parts of Rhizoma Smilacis Chinensiss, 4 parts of YANGKAIKOU, 1 part of Herba lygodii, 1 part of Herba Centellae, with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, adding for the first time 6 times of water gagings decocted 2 hours, add for the second time 6 times of water gagings and decocted 1 hour, collecting decoction filters, it is 1.15～1.20 clear paste that filtrate is condensed into 60 ℃ of relative densities, dry below 80 ℃, get two parts of extract powders, a and polyoxyethylene monostearate S-40 portion of PEG4000, mix homogeneously, fuse in the water-bath, stir evenly, drip and in dimethicone, to become ball, drip apart from 5cm drip footpath 2.5mm/2mm, mix 70 ℃ of ointment temperature, liquid coolant height 70cm promptly gets drop pill.

Embodiments of the invention 8: 10 parts of Radix Rosae Laevigataes, 6 parts of Rhizoma Smilacis Chinensiss, 6 parts of YANGKAIKOU, 4 parts of Herba lygodii, 4 parts of Herba Centellaes, with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, add for the first time 6 times of water gagings and decocted 2 hours, add 6 times of water gagings for the second time and decocted collecting decoction 1 hour, filter, it is 1.15～1.20 clear paste that filtrate is condensed into 60 ℃ of relative densities, and it is an amount of to add aspartame 30g and dextrin, mixing, get about 2/3 medicinal liquid drying, make extract powder, get the residue medicinal liquid again and do binding agent, granulate, make 1000g, promptly get granule.

Embodiments of the invention 9: 8 parts of Radix Rosae Laevigataes, 4 parts of Rhizoma Smilacis Chinensiss, 4 parts of YANGKAIKOU, 1 part of Herba lygodii, 1 part of Herba Centellae, with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae decocts with water secondary, adds 6 times of water gagings for the first time and decocts 2 hours, adding for the second time 6 times of water gagings decocted 1 hour, collecting decoction filters, and it is 1.15～1.20 clear paste that filtrate is condensed into 60 ℃ of relative densities, dry below 80 ℃, dry extract is broken into fine powder, adds starch and adjusts total amount, mix homogeneously, granulate, 50～60 ℃ of dryings, the granulate that sieves incapsulates, make 1000, promptly get capsule.

In the embodiment of the invention, used Herba Centellae can substitute with the asiaticoside that the Herba Centellae of given weight is extracted.

Claims (12)

1. treat three gold medal pharmaceutical preparatioies of diseases such as urinary system, it is characterized in that: calculate according to components by weight percent, it is that Radix Rosae Laevigatae 8-10 part, Rhizoma Smilacis Chinensis 4-6 part, YANGKAIKOU 4-6 part, Herba lygodii 1-4 part and Herba Centellae 1-4 part or their extract of corresponding weight portion are made into dispersible tablet, effervescent tablet, granule, capsule, soft capsule, microcapsule, micropill, drop pill, injection, comprise: powder injection formulation, lyophilized injectable powder, acceptable dosage form on the pharmaceuticss such as slow releasing preparation, controlled release preparation, gel, soft extract, extractum and membrane.

2. according to three gold medal pharmaceutical preparatioies of diseases such as the described treatment urinary system of claim 1, it is characterized in that: described preparation is dispersible tablet, soft capsule, micropill, granule, capsule, effervescent tablet or drop pill, and used Herba Centellae can substitute with the asiaticoside that the Herba Centellae of given component is extracted.

3. the preparation method of three gold medal pharmaceutical preparatioies of diseases such as treatment urinary system as claimed in claim 1 or 2, it is characterized in that: with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, 2 hours for the first time, 1 hour for the second time, collecting decoction filtered, survey when filtrate is condensed into 60 ℃ of relative densities and be the clear paste of 1.15-1.20, and then make different preparations respectively.

4. according to the preparation method of three gold medal pharmaceutical preparatioies of diseases such as the described treatment urinary system of claim 3, it is characterized in that: the dispersible tablet in the described preparation prepares like this: with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, 2 hours for the first time, 1 hour for the second time, collecting decoction, filter, survey when filtrate is condensed into 60 ℃ of relative densities and be the clear paste of 1.15-1.20, drying, pulverize, get extract powder, press extract powder: carboxymethyl starch sodium: modified starch: microcrystalline Cellulose=20: 5: 5: 2 part by weight, with extract powder and carboxymethyl starch sodium, modified starch, the microcrystalline Cellulose mixing that sieves, add suitable quantity of water and make soft material, granulate, granulate is pressed extract powder: the part by weight of magnesium stearate=7: 2 again, add magnesium stearate, adopt the PY129 rotary tablet machine, pressure is 6～7kg, and rotating speed is 25r/min, tabletting, promptly.

5. according to the preparation method of three gold medal pharmaceutical preparatioies of diseases such as the described treatment urinary system of claim 3, it is characterized in that: the pellet in the described preparation prepares like this: with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, for the first time adding 6 times of decoctings boiled 2 hours, for the second time adding 6 times of decoctings boiled 1 hour, collecting decoction, filter, it is 1.15～1.20 thick paste that filtrate is condensed into 60 ℃ of relative densities, at 60～70 ℃ of vacuum dryings, pulverize, add an amount of starch, with 90% ethanol and soybean oil system soft material, extruding-round as a ball pill, drying, make 1000g, promptly.

6. according to the preparation method of three gold medal pharmaceutical preparatioies of diseases such as the described treatment urinary system of claim 5, it is characterized in that: the pellet in the described preparation prepares like this: with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, for the first time adding 6 times of decoctings boiled 2 hours, for the second time adding 6 times of decoctings boiled 1 hour, collecting decoction filters, and it is 1.15～1.20 thick paste that filtrate is condensed into 60 ℃ of relative densities, at 60～70 ℃ of vacuum dryings, pulverize, add an amount of starch, with 90% ethanol and soybean oil system soft material, the soft material that makes micropill mechanism ball, wet feed pushed the 0.8mm sieve aperture, the wet grain of strip cuts off round as a ball, and 50～60 ℃ of drying and mouldings are crossed 10 mesh sieves and selected ball, dry, envionmental humidity should be controlled at below 54%, makes 1000g, promptly.

7. according to the preparation method of three gold medal pharmaceutical preparatioies of diseases such as the described treatment urinary system of claim 3, it is characterized in that: the soft capsule in the described preparation prepares like this: with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, adding for the first time 6 times of water gagings decocted 2 hours, adding for the second time 6 times of water gagings decocted 1 hour, collecting decoction, filter, it is 1.15～1.20 clear paste that filtrate is condensed into 60 ℃ of relative densities, dry below 80 ℃, dry extract is pulverized, cross sieve No. five, add soybean oil, Cera Flava is an amount of, mixing, be pressed into 1000 of soft capsules, promptly.

8. according to the preparation method of three gold medal pharmaceutical preparatioies of diseases such as the described treatment urinary system of claim 7, it is characterized in that: the soft capsule in the described preparation prepares like this: with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, adding for the first time 6 times of water gagings decocted 2 hours, adding for the second time 6 times of water gagings decocted 1 hour, collecting decoction, filter, it is 1.15～1.20 clear paste that filtrate is condensed into 60 ℃ of relative densities, dry below 80 ℃, dry extract is pulverized, and crosses sieve No. five, press medication amount: substrate amount=1: 1 adding soybean oil, 5% Cera Flava, mixing; The capsule shells prescription is gelatin 100g: glycerol 45g: water 100g; Batchingization adhesive tape part is: weigh batching, in the inputization glue jar, merceration is warming up to 65 ± 5 ℃ gradually after 30 minutes, stirred 5 hours and simultaneously evacuation remove bubble, treat evenly back blowing of sizing material, incapsulate after the filtration in the sizing material bucket of machine; During pelleting the sizing material bucket of insulation and the spice bucket of room temperature are delivered to the capsule machine top, be connected with machine, the debugging pellet press, 65 ℃ of gelatin box temperature controls, mould rotating speed 2.0 is rolled in 45 ℃ of sprinkler body temperature controls, rubber thickness 0.8mm, 18～25 ℃ of indoor temperatures, relative humidity＜40%; In conveyer belt was delivered to rotating cage, rotating cage was blown a cold wind over while rotating through the soft capsule of pellet press extrusion, rotated typing dry about 2 hours; The soft gelatin capsule of cold air drying is contained in clean rustless steel charging tray splendid attire in rotating cage, moves to about 22 ℃ of temperature, and airing is 48 hours in the hothouse of relative humidity below 40%, and constantly stirs, and surveys capsule moisture and is being dry suiting below 10%; Be pressed into 1000 of soft capsules, promptly.

9. according to the preparation method of three gold medal pharmaceutical preparatioies of diseases such as the described treatment urinary system of claim 3, it is characterized in that: the effervescent tablet in the described preparation prepares like this: with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, adding for the first time 6 times of water gagings decocted 2 hours, adding for the second time 6 times of water gagings decocted 1 hour, collecting decoction filters, and it is 1.15～1.20 clear paste that filtrate is condensed into 60 ℃ of relative densities, dry below 80 ℃, dry extract is pulverized, and adds 8% sodium bicarbonate, 8% citric acid, 1% aspartame pulverize separately is with the medicated powder mix homogeneously, granulate, drying, tabletting, coating, coating material: internal layer uses PVP to add titanium dioxide, the outer acrylic resin II that uses, during 40 ℃ of sheet bed tempertaures, jet velocity 7.0ml/kgmin, promptly.

10. according to the preparation method of three gold medal pharmaceutical preparatioies of diseases such as the described treatment urinary system of claim 3, it is characterized in that: the drop pill in the described preparation prepares like this: with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, adding for the first time 6 times of water gagings decocted 2 hours, adding for the second time 6 times of water gagings decocted 1 hour, collecting decoction, filter, it is 1.15～1.20 clear paste that filtrate is condensed into 60 ℃ of relative densities, dry below 80 ℃, get two parts of extract powders, a and the polyoxyethylene monostearate S-40 portion of PEG4000, mix homogeneously fuses in the water-bath, stir evenly, drip and in dimethicone, to become ball, drip, mix 70 ℃ of ointment temperature apart from 5cm drip footpath 2.5mm/2mm, liquid coolant height 70cm promptly gets drop pill.

11. preparation method according to three gold medal pharmaceutical preparatioies of diseases such as the described treatment urinary system of claim 3, it is characterized in that: the granule in the described preparation prepares like this: with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, adding for the first time 6 times of water gagings decocted 2 hours, adding for the second time 6 times of water gagings decocted 1 hour, collecting decoction filters, and it is 1.15～1.20 clear paste that filtrate is condensed into 60 ℃ of relative densities, it is an amount of to add aspartame 30g and dextrin, mixing is got about 2/3 medicinal liquid drying, makes extract powder, get the residue medicinal liquid again and do binding agent, granulate, make 1000g, promptly.

12. preparation method according to three gold medal pharmaceutical preparatioies of diseases such as the described treatment urinary system of claim 3, it is characterized in that: the capsule in the described preparation prepares like this: with Radix Rosae Laevigatae, Rhizoma Smilacis Chinensis, YANGKAIKOU, Herba lygodii, Herba Centellae, decoct with water secondary, add for the first time 6 times of water gagings and decocted 2 hours, add 6 times of water gagings for the second time and decocted collecting decoction 1 hour, filter, it is 1.15～1.20 clear paste that filtrate is condensed into 60 ℃ of relative densities, and dry below 80 ℃, dry extract is broken into fine powder, add starch and adjust total amount, mix homogeneously is granulated 50～60 ℃ of dryings, granulate sieves, incapsulate, make 1000, promptly.

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