Summary of the invention
The object of the present invention is to provide a kind of new pharmaceutical preparation and preparation method thereof, said preparation mainly by medicine such as Bulbus Lilii, Poria, Radix Scrophulariae, Rhizoma Chuanxiong, Endothelium Corneum Gigeriae Galli, the Radix Linderae, Rhizoma Alismatis, Radix Ophiopogonis, Radix Notoginseng, the Rhizoma Atractylodis Macrocephalae, Radix Angelicae Sinensis, Herba Artemisiae Scopariae, Radix Sanguisorbae, Pollen Typhae, Rhizoma Corydalis, the Radix Paeoniae Alba, Herba Dendrobii, Rhizoma Anemones Altaicae and suitably adjuvant be prepared from; Supplementary product kind of the present invention, consumption and principal agent reasonable mixture ratio, the preparation that makes both can keep former dosage form to be easy to characteristics such as oral, that absorption is rapid, transportation, easy to carry simultaneously, steady quality, overcome the shortcoming that former preparation is preserved, carried inconvenience, met the modern requirement of Chinese medicine preparation.
The present invention is achieved by the following technical solutions:
A kind of ' Mo Luo ' granule for treating atrophic gastritis for the treatment of gastropathy is characterized in that, counts by weight percentage, and it is mainly by sieve extract powder 20-40% that rubs, and adjuvant 60-80% is prepared from.Adjuvant comprises diluent, correctives; Count by weight percentage, diluent accounts for 59-80%, and correctives accounts for 0-1%.Diluent comprises one or more in starch, dextrin, the lactose; Correctives comprises one or more in stevioside, betanin, aspartame, glycyrrhizin, the saccharin sodium.Preferable absorbent is a dextrin; Correctives is an aspartame.
Described sieve extract powder that rubs mainly is made of by weight following raw material:
0.3 part of Bulbus Lilii 1.2 parts of Poria, 1.2 portions of Radix Scrophulariaes, 0.9 part of Endothelium Corneum Gigeriae Galli of 1.5 parts of Rhizoma Chuanxiongs (stir-fry)
0.6 part of the Radix Linderae 0.9 part of 0.3 part of Rhizoma Atractylodis Macrocephalae of 1.5 portions of Radix Notoginseng Radix Ophiopogonis of 0.9 portion of Rhizoma Alismatis (parched with bran)
1.2 parts of Radix Angelicae Sinensis 0.9 portion of Herba Artemisiae Scopariae, 1.2 portions of Radix Sanguisorbaes, 0.9 part of Rhizoma Corydalis of 1.5 parts of Pollen Typhaes (processed with vinegar)
2.0 parts of the Radix Paeoniae Alba 3.0 parts of Herba Dendrobiis, 0.9 part of Mel of 1.5 portions of Rhizoma Anemones Altaicaes (refining).
Granule of the present invention is preparation like this: above 18 flavor medical materials add 6-10 times of water gaging and decoct 1-3 time, each 1-3 hour, collecting decoction filters, and filtrate is concentrated into the clear paste of relative density 1.10-1.15 (50-60 ℃), adding ethanol makes and contains the alcohol amount and reach 60-80%, left standstill 48 hours, and filtered, reclaim ethanol, and be concentrated into the clear paste that relative density is 1.05 (50-60 ℃), add Mel, stir evenly, continue to be concentrated into the thick paste that relative density is 1.25-1.30 (50-60 a ℃), dry, pulverize, add right amount of auxiliary materials, mixing, granulate, drying, packing, promptly.
Preferred method for making is: above 18 flavor medical materials add 8 times of water gagings and decoct secondary, each 2 hours, collecting decoction filters, and filtrate is concentrated into the clear paste of relative density 1.10-1.15 (50~60 ℃), adding ethanol makes and contains the alcohol amount and reach 70%, left standstill 48 hours, and filtered, reclaim ethanol, and be concentrated into the clear paste that relative density is 1.05 (50-60 ℃), add Mel, stir evenly, continue to be concentrated into the thick paste that relative density is 1.25-1.30 (50-60 a ℃), drying under reduced pressure, pulverize, adding diluent and correctives are an amount of, mixing, granulate, drying, packing, promptly.
At prior art, solvent load during the present invention extracts it has carried out the comparatively examination of system, aspect moulding process, at its pharmaceutical properties, kind, consumption to adjuvant have carried out a large amount of experiments, the adjuvant and the principal agent reasonable mixture ratio of screening, technology is rationally feasible through lab scale, pilot scale, stable and controllable for quality, the preparation that makes simultaneously not only both can keep former dosage form to be easy to characteristics such as oral, that absorption is rapid, transportation, easy to carry simultaneously, steady quality, overcome the shortcoming that former preparation is preserved, carried inconvenience, met the modern requirement of Chinese medicine preparation.
The inventor finds that in development process kind, the consumption of adjuvant have considerable influence to it, and for this reason, the applicant has carried out a series of experiments, and is rationally feasible, quality controllable with proof technology of the present invention, to guarantee the beneficial effect of medicine.
Experimental example 1: Study on extraction
Take by weighing medical material Bulbus Lilii 36g, Poria 36g, Radix Scrophulariae 45g, Rhizoma Chuanxiong 27g, Endothelium Corneum Gigeriae Galli (stir-fry) 9g, Radix Linderae 27g, Rhizoma Alismatis 27g, Radix Ophiopogonis 45g, Radix Notoginseng 9g, the Rhizoma Atractylodis Macrocephalae (parched with bran) 18g, Radix Angelicae Sinensis 27g, Herba Artemisiae Scopariae 36g, Radix Sanguisorbae 45g, Pollen Typhae 27g, Rhizoma Corydalis (processed with vinegar) 36g, Radix Paeoniae Alba 90g, Herba Dendrobii 45g, Rhizoma Anemones Altaicae 27g and be mixed into portion, totally 3 parts, add 6 times of amounts, 8 times of amounts, 10 times of water gagings respectively, decoct 2 times, each 2 hours, concentrated, dry, get three parts of dry extracts, with the peoniflorin is evaluation index, the results are shown in Table 1.
Table 1 amount of water preference data table
Sample number inventory (g) amount of water (doubly) peoniflorin total amount (mg)
1 612.0 6 93.2
2 612.0 8 110.7
3 612.0 10 112.2
Above result shows, add water 6-10 doubly measure basic can extracts active ingredients is complete, paeoniflorin content can satisfy prescription substantially, but it is complete than 6 times of amounts to add 8 times of extractions with 10 times of water, and the extraction effect of 8 times of amounts and 10 times of amounts is suitable, so take all factors into consideration from practical factors such as energy consumptions, preferably add 8 times of amounts of water.
The research of experimental example 2 moulding processs
2.1. the screening of diluent:
The diluent that Chinese medicine granules is commonly used is starch, dextrin, lactose etc.Below its diluent commonly used is screened, the results are shown in Table 2.
The screening of table 2 diluent kind
Principal agent (g) starch (g) lactose (g) dextrin (g) dissolubility mouldability
30 60--general molding
30-60-good molding
30--60 good molding
30 30 30-good molding
30 30-30 good molding
30-30 30 good molding
30 20 20 20 good molding
Table 2 shows no matter above-mentioned adjuvant uses separately or be used, and can both play effect, but because this granule is a soluble granule, and the water solublity of starch is general, the lactose price is higher relatively; And dextrin is dissolved in hot water, and hygroscopicity is little, and cheap, in conjunction with reduce supplementary product consumption as far as possible, so preferred dextrin is a diluent.Below its consumption is examined or check, as follows:
Get Bulbus Lilii, Poria, Radix Scrophulariae, Rhizoma Chuanxiong, Endothelium Corneum Gigeriae Galli (stir-fry), the Radix Linderae, Rhizoma Alismatis, Radix Ophiopogonis, Radix Notoginseng, the Rhizoma Atractylodis Macrocephalae (parched with bran), Radix Angelicae Sinensis, Herba Artemisiae Scopariae, Radix Sanguisorbae, Pollen Typhae, Rhizoma Corydalis (processed with vinegar), the Radix Paeoniae Alba, Herba Dendrobii, Rhizoma Anemones Altaicae adds 8 times of water gagings and decocts secondary, each 2 hours, collecting decoction filters, and filtrate is concentrated into the clear paste of relative density 1.10~1.15 (50~60 ℃), add ethanol and make and contain the alcohol amount and reach 70%, left standstill 48 hours, filter, reclaim ethanol, and be concentrated into the clear paste that relative density is 1.05 (50~60 ℃), add Mel, stir evenly, continue to be concentrated into the thick paste that relative density is 1.25~1.30 (50~60 ℃), drying under reduced pressure, pulverize,, add 1.5 times of medicated powder amount respectively gained medicated powder, 2 times, 3 times, 4 times dextrin, mixing is used the alcohol granulation of debita spissitudo, drying respectively.The results are shown in Table 3.
The selection of table 3 supplementary product consumption
Medicated powder (g) dextrin (g) granulating efficiency
15 22.5 made granules are soft partially, and grain forming is general
15 30 made soft material soft durometer are moderate; The grain forming effect is better
15 45 made soft material soft durometer are moderate; Grain forming is effective
15 60 made soft materials are hard partially; Grain forming is general
Above result shows: the diluent consumption is when 60-80%, and granule all can molding.But experiment finds, adds 2 times in dextrin, 3 times of amount persons (accounting for the 66-75% of prescription total amount) soft material viscosity is suitable, easy-formation, good characters; Add 1.5 times of amount persons of dextrin (account for prescription total amount 60%), soft material is soft partially, and the sticking sieve of part is arranged during granulation; When adding dextrin and be 4 times of amounts (account for prescription total amount 80%), soft material is hard partially, and molding is general; So the preferred dextrin that adds 2~3 times of amounts of medicated powder, the grain forming that makes when promptly adding the dextrin of the 66-75% that accounts for the prescription total amount is good.
2.2 the screening of correctives:
Sweeting agent commonly used has: stevioside, betanin, aspartame, glycyrrhizin and saccharin sodium etc., below it is examined or check, and the results are shown in Table 4.
The screening of table 4 diluent kind
Principal agent dextrin stevioside betanin aspartame glycyrrhizin saccharin sodium mouthfeel
(g) (g) (g) (g) (g) (g) (g)
3.2 6.8-----the Lve hardship
3.2 6.75 0.05----good
3.2 6.75-0.05---good
3.2 6.75--0.05 is good
3.2 6.75--0.05-good
3.2 6.75----0.05 is good
3.2 6.70 0.05 0.05---better
3.2 6.72-0.04 0.04--good
3.2 6.70 0.02 0.02 0.04-0.02 is good
3.2 6.74 0.02-0.02-0.02 is better
The above results shows, above-mentioned correctives no matter use separately or any one and other any or more than one are when being used, suit one's taste and all have some improvement, consumption to its 0-1.0% has carried out trial test simultaneously, because added Mel in the former prescription, when not adding sweeting agent, mouthfeel is bitterness slightly, but accepted by the patient than being easier to, so being the correctives of 0-1.0%, consumption can both meet the demands substantially; But because betanin is alkalescence, may be influential to composition, glycyrrhizin is the class adrenocortical hormones, taking for a long time to influence human electrolyte's metabolism; Saccharin sodium is a synthetic sweetener, and stevioside sweet taste mouthfeel is general, considers to reduce supplementary product consumption and kind simultaneously as far as possible, and through examination, preferred aspartame is a correctives. do further examination in the face of its consumption down.
Get the granule quarter that does not add sweeting agent that has prepared, the aspartame that adds finished product preparation 0%, 0.3%, 0.5%, 1.0% amount respectively, after boiled water dashes, the mouthfeel of 0.3% amount is bitterness slightly, the mouthfeel of 1.0% amount is slightly sweet, and the mouthfeel of 0.5% amount is moderate, so the preferred aspartame that adds output 0.5%.
2.3. determining of method of granulating
Medical material is extracted, and drying obtains water and carries medicated powder, is divided into 5 parts, carries out the comparison of Different concentrations of alcohol granulating efficiency, selects the ethanol of concentration range 70~90% to test (23 ℃ of room temperatures; Humidity 50%), it the results are shown in Table 5.
Table 5 granulating efficiency comparison sheet
Sequence number concentration of alcohol (%) granulating efficiency
1 70 molding are general
2 75 made soft material soft durometer are moderate substantially; Molding is better
3 80 made soft material soft durometer are moderate; The grain forming effect is better
4 85 made soft material soft durometer are moderate; Grain forming is effective
5 90 molding are general
As seen from the above table, during the 70-90% alcohol granulation, this grain forming can satisfy the preparation requirement substantially, but the 80-85% alcohol granulation is for well.
Experimental example 3: the mensuration of physical characteristic
3.1 mobile mensuration
Get dried granule (water content is 2%) 50g, granule is flowed in the culture dish through a funnel, treat the height of granule circular cone on the mensuration culture dish of static back, measure the diameter (2R) of granule conical base by graph paper, calculate (tg α=H/R), the results are shown in Table 6 angle of repose.
Table 6 particulate angle of repose
Experiment angle of repose (α °)
1 28.17
2 29.17
3 30.75
4 28.66
5 32.62
Meansigma methods 29.91
As seen from the above table, particulate flowability meets the needs of particle manufacture.
3.2 the mensuration of granule critical relative humidity
For whether easily the granule moisture absorption is described, we have carried out the mensuration of critical relative humidity, concrete grammar is as follows: it is an amount of to get granule, after being dried to constant weight, put into the granule of thick about 2mm in the weighing botle bottom of constant weight, accurately weighing is placed in the exsiccator of the listed supersaturated aqueous solution that fills 7 kinds of variable concentrations sulphuric acid or different salt respectively of following table (the weighing bottle cap is opened), and maintenance is after 72 hours in 25 constant incubators, weigh, calculate the moisture absorption percentage rate.The results are shown in Table 7.
Moisture absorption counting rate meter under the different relative humiditys of table 7
Sulfuric acid concentration 54% 48% 44% NaBr NaCl KCl KNO3
Or saline solution
RH%(25℃) 29.55 40.52 48.52 57.70 75.28 84.26 92.48
Hydroscopicity (%) 0.37 0.64 0.98 4.77 12.40 18.98 25.23
Concrete embodiment
Embodiment 1: the shared umber of each raw material in massage sieve granule, get following recipe quantity raw material:
Bulbus Lilii 120g Poria 120g Radix Scrophulariae 150g Rhizoma Chuanxiong 90g
Endothelium Corneum Gigeriae Galli (stir-fry) 30g Radix Linderae 90g Rhizoma Alismatis 90g 150g Radix Ophiopogonis
The Rhizoma Atractylodis Macrocephalae (parched with bran) 60g Radix Notoginseng 30g Radix Angelicae Sinensis 90g Herba Artemisiae Scopariae 120g
Rhizoma Corydalis (processed with vinegar) 120g Radix Sanguisorbae 150g Pollen Typhae 90g Radix Paeoniae Alba 300g
Herba Dendrobii 150g Rhizoma Anemones Altaicae 90g Mel (refining) 200g
More than 18 flavor medical materials, add 8 times of water gagings and decoct secondaries, each 2 hours, collecting decoction filters, and filtrate is concentrated into the clear paste of relative density 1.10~1.15 (50~60 ℃), add ethanol and make and contain the alcohol amount and reach 70%, left standstill 48 hours, filter, reclaim ethanol, and be concentrated into the clear paste that relative density is 1.05 (50~60 ℃), add Mel, stir evenly, continue to be concentrated into the thick paste that relative density is 1.25~1.30 (50~60 ℃), drying under reduced pressure is pulverized, get fine powder, nearly weigh 312g, add dextrin 683g and aspartame 5g, mixing, use 85% alcohol granulation, drying is made 1000g, promptly.
Embodiment 2: the shared umber of each raw material in massage sieve granule, get following recipe quantity raw material:
Bulbus Lilii 120g Poria 120g Radix Scrophulariae 150g Rhizoma Chuanxiong 90g
Endothelium Corneum Gigeriae Galli (stir-fry) 30g Radix Linderae 90g Rhizoma Alismatis 90g 150g Radix Ophiopogonis
The Rhizoma Atractylodis Macrocephalae (parched with bran) 60g Radix Notoginseng 30g Radix Angelicae Sinensis 90g Herba Artemisiae Scopariae 120g
Rhizoma Corydalis (processed with vinegar) 120g Radix Sanguisorbae 150g Pollen Typhae 90g Radix Paeoniae Alba 300g
Herba Dendrobii 150g Rhizoma Anemones Altaicae 90g Mel (refining) 200g
More than 18 flavor medical materials, add 6 times of water gagings and decoct each 1 hour 3 times, collecting decoction filters, and filtrate is concentrated into the clear paste of relative density 1.10~1.15 (50~60 ℃), add ethanol and make and contain the alcohol amount and reach 60%, left standstill 48 hours, filter, reclaim ethanol, and be concentrated into the clear paste that relative density is 1.05 (50~60 ℃), add Mel, stir evenly, continue to be concentrated into the thick paste that relative density is 1.25~1.30 (50~60 ℃), drying under reduced pressure is pulverized, get fine powder, nearly weigh 200g, add dextrin 800g, mixing, use 80% alcohol granulation, drying is made 1000g, promptly.
Embodiment 3: the shared umber of each raw material in massage sieve granule, get following recipe quantity raw material:
Bulbus Lilii 120g Poria 120g Radix Scrophulariae 150g Rhizoma Chuanxiong 90g
Endothelium Corneum Gigeriae Galli (stir-fry) 30g Radix Linderae 90g Rhizoma Alismatis 90g 150g Radix Ophiopogonis
The Rhizoma Atractylodis Macrocephalae (parched with bran) 60g Radix Notoginseng 30g Radix Angelicae Sinensis 90g Herba Artemisiae Scopariae 120g
Rhizoma Corydalis (processed with vinegar) 120g Radix Sanguisorbae 150g Pollen Typhae 90g Radix Paeoniae Alba 300g
Herba Dendrobii 150g Rhizoma Anemones Altaicae 90g Mel (refining) 200g
More than 18 flavor medical materials, add 10 times of water gagings and decoct each 3 hours 3 times, collecting decoction filters, and filtrate is concentrated into the clear paste of relative density 1.10~1.15 (50~60 ℃), add ethanol and make and contain the alcohol amount and reach 80%, left standstill 48 hours, filter, reclaim ethanol, and be concentrated into the clear paste that relative density is 1.05 (50~60 ℃), add Mel, stir evenly, continue to be concentrated into the thick paste that relative density is 1.25~1.30 (50~60 ℃), drying under reduced pressure is pulverized, get fine powder, nearly weigh 400g, add lactose 590g and glycyrrhizin 10g, mixing, use 85% alcohol granulation, drying is made 1000g, promptly.
Embodiment 4: the shared umber of each raw material in massage sieve granule, get following recipe quantity raw material:
Bulbus Lilii 120g Poria 120g Radix Scrophulariae 150g Rhizoma Chuanxiong 90g
Endothelium Corneum Gigeriae Galli (stir-fry) 30g Radix Linderae 90g Rhizoma Alismatis 90g 150g Radix Ophiopogonis
The Rhizoma Atractylodis Macrocephalae (parched with bran) 60g Radix Notoginseng 30g Radix Angelicae Sinensis 90g Herba Artemisiae Scopariae 120g
Rhizoma Corydalis (processed with vinegar) 120g Radix Sanguisorbae 150g Pollen Typhae 90g Radix Paeoniae Alba 300g
Herba Dendrobii 150g Rhizoma Anemones Altaicae 90g Mel (refining) 200g
More than 18 flavor medical materials, add 7 times of water gagings and decocted 3 hours, filter, filtrate is concentrated into the clear paste of relative density 1.10~1.15 (50~60 ℃), adds ethanol and makes and contain the alcohol amount and reach 75%, leaves standstill 48 hours, filter, reclaim ethanol, and be concentrated into the clear paste that relative density is 1.05 (50~60 ℃), add Mel, stir evenly, continue to be concentrated into the thick paste that relative density is 1.25~1.30 (50~60 ℃), drying under reduced pressure is pulverized, get fine powder, nearly weigh 285g, add dextrin 570g, starch 139g and aspartame 3g, betanin 3g, mixing, use 90% alcohol granulation, drying is made 1000g, promptly.
Embodiment 5: the shared umber of each raw material in massage sieve granule, get following recipe quantity raw material:
Bulbus Lilii 120g Poria 120g Radix Scrophulariae 150g Rhizoma Chuanxiong 90g
Endothelium Corneum Gigeriae Galli (stir-fry) 30g Radix Linderae 90g Rhizoma Alismatis 90g 150g Radix Ophiopogonis
The Rhizoma Atractylodis Macrocephalae (parched with bran) 60g Radix Notoginseng 30g Radix Angelicae Sinensis 90g Herba Artemisiae Scopariae 120g
Rhizoma Corydalis (processed with vinegar) 120g Radix Sanguisorbae 150g Pollen Typhae 90g Radix Paeoniae Alba 300g
Herba Dendrobii 150g Rhizoma Anemones Altaicae 90g Mel (refining) 200g
More than 18 flavor medical materials, add 9 times of water gagings and decoct each 1.5 hours 2 times, collecting decoction filters, and filtrate is concentrated into the clear paste of relative density 1.10~1.15 (50~60 ℃), add ethanol and make and contain the alcohol amount and reach 70%, left standstill 48 hours, filter, reclaim ethanol, and be concentrated into the clear paste that relative density is 1.05 (50~60 ℃), add Mel, stir evenly, continue to be concentrated into the thick paste that relative density is 1.25~1.30 (50~60 ℃), drying under reduced pressure is pulverized, get fine powder, nearly weigh 298g, add dextrin 399g, lactose 298g and stevioside 2g, saccharin sodium 3g, mixing, use 70% alcohol granulation, drying is made 1000g, promptly.
Embodiment 6: the shared umber of each raw material in massage sieve granule, get following recipe quantity raw material:
Bulbus Lilii 120g Poria 120g Radix Scrophulariae 150g Rhizoma Chuanxiong 90g
Endothelium Corneum Gigeriae Galli (stir-fry) 30g Radix Linderae 90g Rhizoma Alismatis 90g 150g Radix Ophiopogonis
The Rhizoma Atractylodis Macrocephalae (parched with bran) 60g Radix Notoginseng 30g Radix Angelicae Sinensis 90g Herba Artemisiae Scopariae 120g
Rhizoma Corydalis (processed with vinegar) 120g Radix Sanguisorbae 150g Pollen Typhae 90g Radix Paeoniae Alba 300g
Herba Dendrobii 150g Rhizoma Anemones Altaicae 90g Mel (refining) 200g
More than 18 flavor medical materials, add 8 times of water gagings and decoct secondaries, each 2 hours, collecting decoction filters, and filtrate is concentrated into the clear paste of relative density 1.10~1.15 (50~60 ℃), add ethanol and make and contain the alcohol amount and reach 70%, left standstill 48 hours, filter, reclaim ethanol, and be concentrated into the clear paste that relative density is 1.05 (50~60 ℃), add Mel, stir evenly, continue to be concentrated into the thick paste that relative density is 1.25~1.30 (50~60 ℃), drying under reduced pressure, pulverize, get fine powder, nearly weigh 320g, add lactose 640g, starch 35g and aspartame 2g, stevioside 2g, glycyrrhizin 1g mixing, use 80% alcohol granulation, drying is made 1000g, promptly.