Summary of the invention
The present invention is directed to the deficiency of existing oral mushroom liquor dosage form, it is little to have developed the medicine volume, is easy to carry, accumulating steady quality, good absorbing, the low Decoction of Four-Drug Juice drops of packing production cost.
The present invention is achieved by the following technical solutions:
A kind of Decoction of Four-Drug Juice drop pill, raw material is made up of the Radix Aucklandiae, Fructus Aurantii, Semen Arecae and four kinds of medical materials of the Radix Linderae, is used as medicine after extracting, and substrate is: polyethylene glycol 6000 or Macrogol 4000 or poloxamer;
The weight portion of each major ingredient of distinguishing the flavor of is: 3 parts of the Radix Aucklandiae, 3 parts of Fructus Aurantiis, 3 parts of Semen Arecaes, 3 parts of the Radixs Linderae;
Medicinal substances extract: substrate is 1: 1~1: 10.
A kind of Decoction of Four-Drug Juice drop pill, medicinal substances extract: substrate is 1: 2~1: 6.
A kind of preparation method of Decoction of Four-Drug Juice drop pill is to prepare according to the following steps:
(1) with the Radix Aucklandiae, Fructus Aurantii, Semen Arecae and Radix Linderae four Chinese medicine material, with way of distillation distillation 1~4 hour, extraction volatile oil or collection Aromatic water adopted times its cyclodextrin saturated water solution method enclose to collect volatile oil;
(2) surplus materials of having removed volatile oil in the above-mentioned steps is filtered, the decocting that medicinal residues add 8~12 times of amounts boils twice, decocts 0.2~1 hour for the first time, decocts 0.2~1 hour for the second time, filters, and remerges medicinal liquid, is evaporated to clear paste;
(3) the gained clear paste is added ethanol and make and contain alcohol amount and reach 60%~90%, cold preservation 10~14 hours filters, and filtrate recycling ethanol adds 2~4 times of water gagings and stirs after do not have the alcohol flavor, and cold preservation is 10~14 hours again, filters, and filtrate decompression is concentrated into thick paste, and is standby;
(4) in said medicine: the ratio of substrate, taking polyethylene glycol in addition, heating and melting adds thick paste and volatile oil, stirs evenly, and it is standby to obtain containing the fused solution of drug extract and substrate or emulsion or suspension;
(5) the water dropper bore of adjustment drop pill machine, internal diameter is 1~5mm, external diameter 2~10mm; The temperature heating of dropping-pill machine head also remains on 30 ℃~100 ℃; The condensing agent cooling also remains on 50 ℃~-6 ℃;
(6) etc. after the temperature adjustment of the size adjusting of water dropper internal diameter and external diameter and water dropper and condensing agent all reaches requirement in the above-mentioned steps (5), the fused solution that contains drug extract and substrate that obtains or emulsion or suspension are put into the water dropper jar of drop pill machine;
(7) drug extract, volatile oil or volatile oil clathrate compound and substrate mixture are splashed in the condensing agent, be shrunk to ball, promptly.
A kind of preparation method of Decoction of Four-Drug Juice drop pill, it is described with the Radix Aucklandiae, Fructus Aurantii, Semen Arecae and Radix Linderae four Chinese medicine material, adopt times its cyclodextrin saturated water solution method enclose to collect volatile oil with way of distillation distillation extraction in 3 hours volatile oil or collection Aromatic water, the volatile oil yield of being carried is 85%.
A kind of preparation method of Decoction of Four-Drug Juice drop pill, the decocting that its described medicinal residues add 10 times of amounts boils is advisable, and decocts 0.5 hour for the first time, decocts 0.5 hour for the second time.
A kind of preparation method of Decoction of Four-Drug Juice drop pill, it is described to add ethanol with the gained clear paste and makes and contain alcohol amount and reach 75%, and cold preservation 12 hours filters, and filtrate recycling ethanol adds 3 times of water gagings and stirs and be advisable after do not have the alcohol flavor, and cold preservation is 12 hours again, filters.
A kind of preparation method of Decoction of Four-Drug Juice drop pill, the water dropper bore of its described adjustment drop pill machine, internal diameter the best is 2mm, the best 5mm of external diameter; The temperature of dropping-pill machine head heats and remains on 70 ℃ is advisable; Condensing agent cools off and remains on-5 ℃ is advisable.
A kind of preparation method of Decoction of Four-Drug Juice drop pill, its described condensing agent are liquid paraffin or dimethicone or vegetable oil.
Oral mushroom liquor is changed system into the Decoction of Four-Drug Juice drop pill, and its advantage is:
(1) this product effective ingredient volatile oil extraction ratio height, determined curative effect can satisfy the needs of extensive patients, further enlarges Clinical Application.
(2) drop pill had both possessed the advantage of solid preparation, as carried accumulating conveniently, and quality is comparatively stable, possesses the advantage of good absorbing again.
(3) to take volume little for this product, is fit to treatment, the especially abdominal postoperative of this disease kind, the patient that gastrointestinal function need recover.
(4) this product inner packing adopts medicinal composite membrane, so in that big production intermediate package cost is lower than former dosage form from now on.
1, Study on extraction
(1) Radix Aucklandiae, Fructus Aurantii, Semen Arecae, Radix Linderae volatile oil definite enclose that reaches volatile oil of extraction time.
Take by weighing the common 300g of four Chinese medicine material such as the Radix Aucklandiae in proportion, add water 3000ml, extract volatile oil with steam distillation, certain hour writes down the volatile oil cumulant at interval, the results are shown in following table:
Table 1:
By last table 1 as can be known, carry oil after 3 hours, the volatilization oil mass tends towards stability substantially, is 3 hours so determine to carry the oil time.Volatile oil is carried out enclose with beta-schardinger dextrin-, and inclusion rate reaches more than 85%, has reduced the loss of effective ingredient volatile oil in the operation.
(2) investigation of amount of water
Medicinal residues after clearly distilling in the primary standard, decoct with water secondary, each 0.5 hour, and not clear and definite each amount of water that decocts, for preferred suitable amount of water, we serve as to follow the tracks of index with proposed clear paste amount and naringin content, and the decoction situation of 8,10,12 times of water gagings is compared, and experimental technique and result are as follows:
The preparation of A, clear paste
Take by weighing four Chinese medicine 300g such as the Radix Aucklandiae in the prescription ratio, add water 3000ml distillation 3 hours, filter, volatile oil device is in addition collected, and medicinal residues add 8,10,12 times of water gagings respectively and decoct secondary, each 0.5h, filtrate merges, and being evaporated to relative density is the clear paste of 1.10 (60-70 ℃), and it is an amount of to take by weighing clear paste, carry out measuring naringin content, the results are shown in following table:
Table 2: different amount of water are to the influence of naringin content
Last table 2 measurement result show 10 times with 12 times of water gagings to put forward in the clear paste naringin amount suitable, all high than 8 times of amounts, consider enrichment process, add 10 times of water gagings decoctions so select for use.
The investigation of B, water precipitating technology amount of water
Take by weighing the common 900g of four Chinese medicine such as the Radix Aucklandiae, extract by above-mentioned preferred technology, being evaporated to relative density is the clear paste of 1.10 (60-70 ℃), add ethanol and make and contain alcohol amount and reach 75%, cold preservation 12 hours filters, filtrate recycling ethanol is equally divided into three parts to the clear paste that does not have the alcohol flavor with it, adds 2,3,4 times of water gagings respectively, stir evenly, cold preservation 12 hours filters, filtrate is condensed into the thick paste that relative density is 1.25-1.30 (60 ℃), measure its naringin content, and observe its sedimentation effect, the results are shown in following table 3.
Table 3
Above table 3 result shows, selects 3 times of water gagings to wash and is advisable.
2, the research of moulding process
For guarantee content in the preparation process evenly, the unanimity of color and luster, the suspension ability of medicine in liquid matrix tested, medicine is added to mixing in fused polyethylene glycol 6000 and the Macrogol 4000, insulation is placed after 6 hours and is observed, medicinal liquid color and luster in liquid polyethylene glycol is even as a result, does not have obvious layering and deposited phenomenon.See the following form 4 through test:
Table 4
Medicine and polyethylene glycols and condensing agent liquid Paraffin, Oleum Arachidis hypogaeae semen, dimethicone all do not have intersolubility, and that polyethylene glycol 6000 drips in the system broken ball than Macrogol 4000 is less, and hardness is good, so determine that polyethylene glycol 6000 is a drop pill substrate; The liquid paraffin sedimentation velocity is moderate, and roundness is good, and hardness is good, so the selection liquid Paraffin is a condensing agent.
3, the optimal process of drop pill
In the preparation technology of drop pill, matrix species, the mixed proportion of medicinal substances extract and substrate, drip the system temperature, water dropper bore, coolant temperature etc. are the key factors of decision drop pill mouldability and presentation quality, on the basis of single factor screening, with PEG6000 is substrate, liquid paraffin is a condensing agent, and (inside/outside mm) is decided to be 2.0/5.0mm to the water dropper bore, to medicine and substrate ratio, the factors such as system temperature, coolant temperature of dripping are carried out preferably.
Table 5 factor level table
Comprehensive above each index optimised process collocation obtains Decoction of Four-Drug Juice drop pill optimised process, and promptly dripping the system temperature is 75 ℃, and coolant temperature is-5 ℃, medicinal substances extract: matter is 1: 2.5.
Pharmacological research for the Decoction of Four-Drug Juice drop pill can be referring to the pharmacological research of Decoction of Four-Drug Juice.
It is pleasant sending down the abnormal ascending QI that this product function cures mainly, the removing food stagnancy pain relieving.Be used for the disease that stagnates in the infant breast food, disease is seen abdominal distention, the uneasiness of suffering from abdominal pain, cry, anorexia poor appetite, diarrhoea or constipation; Person in middle and old age's stagnation of QI, food stagnation disease, disease is seen distension and fullness in the abdomen, stomachache, constipation; And abdominal postoperative promotes the recovery of gastrointestinal function.
Usage and dosage, oral, the 2.5g that is grown up a time, 3 times on the one, one week of the course of treatment; 0.4~0.6g of neonate, 3 times on the one, 2 days courses of treatment; 1.25g of child, 3 times on the one, the 3-5 days course of treatment.
The specific embodiment
Embodiment 1
The preparation method of Decoction of Four-Drug Juice drop pill includes the Radix Aucklandiae, Fructus Aurantii, Semen Arecae and Radix Linderae four Chinese medicine material.
By medicinal substances extract: substrate is to carry out proportioning at 1: 3.
Preparation according to the following steps:
With Radix Aucklandiae 300g, Fructus Aurantii 300g, Semen Arecae 300g and Radix Linderae 300g four Chinese medicine material, extracted volatile oil in 3 hours with way of distillation distillation, volatile oil is collected in extraction volatile oil or the employing of collection Aromatic water doubly its cyclodextrin saturated water solution method enclose; The surplus materials of having removed volatile oil in the preceding step is filtered, and the decocting that medicinal residues add 10 times of amounts boils twice, decocts 0.5 hour for the first time, decocts filtration in 0.5 hour for the second time, remerges medicinal liquid, is evaporated to clear paste; The gained clear paste is added ethanol make and contain alcohol amount and reach 75%, cold preservation 12 hours filters, and filtrate recycling ethanol adds 3 times of water gagings and stirs after do not have the alcohol flavor, and cold preservation is 12 hours again, filters, and filtrate decompression is concentrated into thick paste, and is standby; Taking polyethylene glycol 6000 in addition, heating and melting adds thick paste and volatile oil, stirs evenly, and it is standby to obtain containing the drug extract suspension; Adjust the water dropper bore of drop pill machine, internal diameter is 2mm, external diameter 5mm; The temperature heating of dropping-pill machine head also remains on 70 ℃; Condensing agent is selected liquid paraffin for use, cools off and remains on-5 ℃; After all reaching requirement in the above-mentioned steps Deng the temperature adjustment of the size adjusting of water dropper internal diameter and external diameter and water dropper and liquid paraffin, the suspension that contains drug extract and substrate that obtains is put into the water dropper jar of drop pill machine; Drug extract and substrate mixture are splashed in the liquid paraffin, be shrunk to ball, make 1000g, promptly.
Embodiment 2
The substrate of preparation is selected Macrogol 4000 for use, and all the other are with embodiment 1.
Embodiment 3
The substrate of preparation is selected poloxamer for use, and all the other are with embodiment 1.
Embodiment 4
Condensing agent is selected methyl-silicone oil for use, and all the other are with embodiment 1.
Embodiment 5
Condensing agent is selected Oleum Arachidis hypogaeae semen for use, and all the other are with embodiment 1.
Embodiment 6
By medicinal substances extract: substrate is to carry out proportioning at 1: 3.
Preparation according to the following steps:
With Radix Aucklandiae 300g, Fructus Aurantii 300g, Semen Arecae 300g and Radix Linderae 300g four Chinese medicine material, extracted volatile oil in 3 hours with way of distillation distillation, volatile oil is collected in extraction volatile oil or the employing of collection Aromatic water doubly its cyclodextrin saturated water solution method enclose; The surplus materials of having removed volatile oil in the preceding step is filtered, and the decocting that medicinal residues add 8 times of amounts boils twice, decocts 0.2 hour for the first time, decocts filtration in 0.2 hour for the second time, remerges medicinal liquid, is evaporated to clear paste; The gained clear paste is added ethanol make and contain alcohol amount and reach 60%, cold preservation 10 hours filters, and filtrate recycling ethanol adds 2 times of water gagings and stirs after do not have the alcohol flavor, and cold preservation is 10 hours again, filters, and filtrate decompression is concentrated into thick paste, and is standby; Taking polyethylene glycol 6000 in addition, heating and melting adds thick paste and volatile oil, stirs evenly, and it is standby to obtain containing the drug extract suspension; Adjust the water dropper bore of drop pill machine, internal diameter is 1mm, external diameter 2mm; The temperature heating of dropping-pill machine head also remains on 30 ℃; Condensing agent is selected liquid paraffin for use, cools off and remains on-6 ℃; After all reaching requirement in the above-mentioned steps Deng the temperature adjustment of the size adjusting of water dropper internal diameter and external diameter and water dropper and liquid paraffin, the suspension that contains drug extract and substrate that obtains is put into the water dropper jar of drop pill machine; Drug extract and substrate mixture are splashed in the liquid paraffin, be shrunk to ball, make 1000g, promptly.
Embodiment 7
By medicinal substances extract: substrate is to carry out proportioning at 1: 3.
Preparation according to the following steps:
The preparation method of Decoction of Four-Drug Juice drop pill includes the Radix Aucklandiae, Fructus Aurantii, Semen Arecae and Radix Linderae four Chinese medicine material, according to the following steps preparation:
With Radix Aucklandiae 300g, Fructus Aurantii 300g, Semen Arecae 300g and Radix Linderae 300g four Chinese medicine material, extracted volatile oil in 3 hours with way of distillation distillation, volatile oil is collected in extraction volatile oil or the employing of collection Aromatic water doubly its cyclodextrin saturated water solution method enclose; The surplus materials of having removed volatile oil in the preceding step is filtered, and the decocting that medicinal residues add 12 times of amounts boils twice, decocts 1 hour for the first time, decocts filtration in 1 hour for the second time, remerges medicinal liquid, is evaporated to clear paste; The gained clear paste is added ethanol make and contain alcohol amount and reach 90%, cold preservation 14 hours filters, and filtrate recycling ethanol adds 4 times of water gagings and stirs after do not have the alcohol flavor, and cold preservation is 14 hours again, filters, and filtrate decompression is concentrated into thick paste, and is standby; Taking polyethylene glycol 6000 in addition, heating and melting adds thick paste and volatile oil, stirs evenly, and it is standby to obtain containing the drug extract suspension; Adjust the water dropper bore of drop pill machine, internal diameter is 5mm, external diameter 10mm; The temperature heating of dropping-pill machine head also remains on 100 ℃; Condensing agent is selected liquid paraffin for use, cools off and remains on 50 ℃; After all reaching requirement in the above-mentioned steps Deng the temperature adjustment of the size adjusting of water dropper internal diameter and external diameter and water dropper and liquid paraffin, the suspension that contains drug extract and substrate that obtains is put into the water dropper jar of drop pill machine; Drug extract and substrate mixture are splashed in the liquid paraffin, be shrunk to ball, make 1000g, promptly.
Embodiment 8
By medicinal substances extract: substrate is to carry out proportioning at 1: 4.All the other are with embodiment 1.
Embodiment 9
By medicinal substances extract: substrate is to carry out proportioning at 1: 5.All the other are with embodiment 1.