CN101474409A - Inclusion method of medicament containing volatile component - Google Patents
Inclusion method of medicament containing volatile component Download PDFInfo
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- CN101474409A CN101474409A CNA2008102411296A CN200810241129A CN101474409A CN 101474409 A CN101474409 A CN 101474409A CN A2008102411296 A CNA2008102411296 A CN A2008102411296A CN 200810241129 A CN200810241129 A CN 200810241129A CN 101474409 A CN101474409 A CN 101474409A
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Abstract
The invention discloses an inclusion method for enhancing the stability of drug containing volatile components. Crospovidone is added during the inclusion process of the drug containing the volatile component. The proportions of the drugs and the crospovidone are 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7 or 1:8. Materials can be ground during the inclusion process, and regular organic solvent such as ethanol, aether and the like can also be added. The proportions of the drug and the organic solvents are 2:1, 1:1 or 5:1, wherein the drugs mainly includes volatile traditional Chinese medicine in common use, such as borneol, menthol and the like. The invention, by experiments, proves that the crospovidone can reduce the volatile quantity of model drugs such as the borneol and the menthol, and the action can be promoted by certain mixing method and adding proper solvent.
Description
Technical field
The present invention relates to the inclusion method that a kind of enhancing contains the medicine stability of volatile ingredient.
Background technology
Borneolum Syntheticum, Mentholum are conventional Chinese medicines, and volatility is stronger, because the volatilization of Borneolum Syntheticum, Mentholum, its content descends, off quality, in addition, particularly in solid preparation, because the volatilization of Borneolum Syntheticum, Mentholum, white decorative pattern appears in dosage surface, and white speckle etc. make the preparation outward appearance defective.In the prior art, avoiding Borneolum Syntheticum, the evaporable method of Mentholum mainly is to take β-cyclodextrin inclusion compound, but the subject matter that exists is that supplementary product consumption is big, influences the molding of preparation, and poor stability.
Summary of the invention
The object of the invention is to disclose the inclusion method that a kind of enhancing contains the medicine stability of volatile ingredient.
The present invention seeks to be achieved through the following technical solutions:
Add polyvinylpolypyrrolidone (PVPP) in the enclose process of the medicine that contains volatile ingredient, the ratio of medicine and polyvinylpolypyrrolidone is: 4:1, and 3:1,2:1,1:1,1:2,1:3,1:4,1:5,1:6,1:7 or 1:8 are preferably 1:3 or 1:4; In the enclose process, can also grind; Can also add conventional organic solvent, as: ethanol, ether etc., the ratio of medicine and organic solvent is: 2:1,1:1 or 5:1.
The wherein above-mentioned medicine that contains volatile ingredient comprises Borneolum Syntheticum, Mentholum etc.
Following experimentation further illustrates the influence of PVPP of the present invention to volatile medicine stability.
Application involved in the present invention realizes by following experimental example:
Experimental example 1 and 2 all uses following reagent and instrument:
Reagent is: Mentholum, PVPP (ISP company
), dehydrated alcohol, ether, 95% ethanol, soluble starch;
Instrument is: electric heating constant temperature air dry oven (DHG-9140A type), sartorius electronic balance BS110S.
Experimental example 1 PVPP is to Mentholum study on the stability (ether group)
1. experimental technique
1.1 weighing botle constant weight
Get 36 of weighing botles, numbering is cleaned with distilled water, places clean pallet, 105 ℃ of dryings, and the difference of weighing after the double drying is below 0.3mg; Be dried to constant weight the second time and after each time weigh and carry out after one hour continuing drying under 105 ℃ of rated conditions.
1.2 sample preparation
A group sample is no ether group, and medicine is a Mentholum, and adjuvant is PVPP, and establishing medicine and adjuvant weight ratio is 4:1,3:1,2:1,1:1,1:2,1:3, get it filled thing and adjuvant mixes according to the above ratio, and put in the mortar middling speed and ground 4～5 minutes, in the back transposition valve bag, airtight preservation.And establish the adjuvant contrast, and the medicine contrast, medicine and adjuvant 1:1 mixing are not ground.Two parts of each ratio operation repetitives.
B group sample is the ether group, and establishing medicine and adjuvant weight ratio is 4:1,3:1,2:1,1:1,1:2,1:3, it is a certain amount of to take by weighing Mentholum, puts in the mortar, dripping ether to Mentholum dissolves, add a certain amount of PVPP more according to the above ratio respectively, ground 4～5 minutes, be transferred to valve bag, uncovered 10～12 hours, treat that ether waves most back sealing.And establish the adjuvant contrast, and the medicine contrast, medicine and adjuvant 1:1 mixing are not ground in contrast, and contrast is handled equally with sample.Two parts of each ratio operation repetitives.
1.3 samples weighing
Insert a certain amount of sample (containing Mentholum 1g) in the weighing botle after constant weight, precision is weighed.Above-mentioned sample is put into pallet, place in the baking oven (40 ℃ of constant temperature, air blast), weighed once record data, the remaining percentage rate of computation model medicine in per 24 hours.With the weighing time be abscissa, medicine residue percentage rate is the vertical coordinate mapping.Weighed record data once in per 24 hours.
2. experimental result
2.1 do not have ether group and ether group sample experimental result, see Fig. 1, Fig. 2.
Conclusion: from Fig. 1, Fig. 2 as can be seen, curve linearly descends, each ratio decrease speed difference, evaporable minimum be that medicine/adjuvant is the 1:3 group, maximum is the medicine matched group.Remaining presses the minimizing of the shared percentage ratio of adjuvant and volatile quantity increases.Illustrate that adjuvant has certain Stabilization to the volatility of Mentholum really.
2.2 the grinding group with do not grind group relatively (1:1), see Fig. 3.
The result: from then on Fig. 3 as can be seen, grinding group and do not grind sets of curves and overlap substantially shows that grinding keeps the stability of drug influence little to promoting PVPP.
2.3 each ratio sample is with the ether dissolution sample and directly grind contrast, sees Fig. 4-9.
Result: from Fig. 4-9 as can be seen, do not grind group and grind sets of curves and overlap substantially, show that grinding keeps the stability of drug products influence little to promoting PVPP.
Whether each ratio is with the ether dissolution sample and directly grind contrast, and curve overlaps substantially, illustrate will to mix with PVPP after the sample dissolution earlier with ether again, keeps medicine stabilizing influence little to increasing adjuvant.The volatile quantity of indivedual ether groups is big slightly, and reason may be that volatilization can be taken away a part of Mentholum owing in the medicine remaining ether is arranged, and causes volatile quantity to increase.
Experimental example 2 PVPP are to Mentholum study on the stability (ethanol group)
Whether PVPP meets water or ethanol can make volumetric expansion, can make after the expansion in the volatile ingredient network structure that enter after the expansion more, its consumption is reduced or more can increase stability of drug, for this reason, has carried out following experiment.
1. experimental technique
1.1 weighing botle constant weight
Get 20 of weighing botles, numbering is cleaned with distilled water, places clean pallet, 105 ℃ of dryings, and the difference of weighing after the double drying is below 0.3mg; Be dried to constant weight the second time and after each time weigh and carry out after one hour continuing drying under 105 ℃ of rated conditions.
1.2 sample preparation
A group sample is the dehydrated alcohol group, and medicine is a Mentholum, and adjuvant is PVPP, and solvent is a dehydrated alcohol, and establishing medicine and solvent ratios is 1:1, and 2:1,5:1, get it filled thing and adjuvant dropwise add dehydrated alcohol more according to the above ratio and grind by the 1:1 mixed.Place on the pan paper and spread out, wave most ethanol, put into valve bag and seal.And establish the adjuvant matched group, the medicine matched group is pressed sample treatment and is handled dry grinding group (1:1).Two parts of each ratio operation repetitives.
B group sample is 95% ethanol group, and solvent is 95% ethanol, and establishing medicine and solvent ratios is 1:1,2:1, and 5:1 gets Mentholum and adjuvant with the 1:1 mixed, dropwise adds 95% ethanol more according to the above ratio and grinds.Place on the pan paper and spread out, wave most ethanol, put into valve bag and seal.And establish the adjuvant matched group, and the medicine matched group, starch group (medicine and solvent 5:1) is pressed sample treatment and is handled dry grinding group (medicine and adjuvant 1:1).Two parts of each ratio operation repetitives.
2. experimental result
2.1 dehydrated alcohol and 95% ethanol sample data are relatively seen Figure 10.
Conclusion: as can be seen from Figure 10, curve is linear downward trend, represents with medicine residue percentage rate, and when medicine matched group drug volatilization finished, all the other contained adjuvant group medicine residue percentage rate between 50%～80%.Volatilizing minimum is dehydrated alcohol 1:1 group, maximum is to be adjuvant with starch, and 95% ethanol (5:1) group illustrates that PVPP has certain Stabilization to Mentholum really, but starch group and medicine are compared, and illustrate that starch also has certain Stabilization to Mentholum.
The adjuvant matched group is earlier on a declining curve, fail when possible cause is the preparation sample fully that solvent evaporates is complete, decline be wherein contained solvent.After solvent evaporates was intact, curve then changed in small range.
2.2 with the dehydrated alcohol is each ratio contrast of sample of solvent, sees Figure 11.
The result: as can be seen from Figure 11, when making solvent with dehydrated alcohol, each ratio, medicine residue percentage ratio more helps the Stabilization of adjuvant to medicine a little more than 5:1 when 1:1 and 2:1 when showing the dehydrated alcohol large percentage.And the difference of 1:1 and 2:1 is little, in the time of may being medicine and solvent 2:1, adjuvant has been reached expansible effect.So the two difference is little.
2.3 with 95% ethanol is each ratio data contrast of sample of solvent, sees Figure 12.
The result: as can be seen from Figure 12, when making solvent with 95% ethanol, each ratio, medicine residue percentage ratio shows that a little more than 1:1 95% ethanol more helps the stable of medicine than small scale when 2:1 and 5:1.
2.4 each ratio data of dehydrated alcohol group and 95% ethanol group sample relatively, sees Figure 13.
The result: as can be seen from Figure 13, no matter with 95% ethanol still be dehydrated alcohol be solvent, when using medicine and solvent 2:1, drug volatilization than other ratios more slowly, 95% ethanol 1:1 effect is the poorest, other ratio difference are little.
2.5 different auxiliary material (starch), Figure 14 is seen in the sample contrast of distinct methods (dry grinding).
The result: as can be seen from Figure 14, as adjuvant, it is the adjuvant group that medicine residue percentage rate is significantly less than with PVPP, shows that PVPP has certain Stabilization to Mentholum with starch.Solubilizer grinding group medicine residue percentage rate is not lower than the solubilizer group, shows that adding solvent in process of lapping can promote PVPP to the stability of drug effect.
Experimental example 3 and 4 all uses following reagent and instrument:
Reagent is: Borneolum Syntheticum, PVPP (ISP company
), dehydrated alcohol, ether, 95% ethanol, lactose, soluble starch;
Instrument is: electric heating constant temperature air dry oven (DHG-9140A type), sartorius electronic balance BS110S.
Experimental example 3 PVPP are to Borneolum Syntheticum study on the stability (ether group)
1. experimental technique
1.1 weighing botle constant weight
Get 36 of weighing botles, numbering is cleaned with distilled water, places clean pallet, 105 ℃ of dryings, and the difference of weighing after the double drying is below 0.3mg; Be dried to constant weight the second time and after each time weigh and carry out after one hour continuing drying under 105 ℃ of rated conditions.
1.2 sample preparation
A group sample is no ether group, and medicine is a Borneolum Syntheticum, and adjuvant is PVPP, and establishing medicine and adjuvant weight ratio is 1:3,1:2,1:1,2:1,3:1,4:1; get Borneolum Syntheticum and adjuvant with above-mentioned mixed put in the mortar middling speed and ground 4～5 minutes, in the back transposition valve bag, airtight preservation.And establish adjuvant contrast, and the medicine contrast, medicine mixes with adjuvant 1:1 and does not grind group.Two parts of each ratio operation repetitives.
B group sample is the ether group, and establishing medicine and adjuvant weight ratio is 1:3,1:2,1:1,2:1,3:1,4:1, it is a certain amount of to take by weighing Borneolum Syntheticum, puts in the mortar, drip ether and make the Borneolum Syntheticum dissolving, add a certain amount of PVPP more according to the above ratio respectively, ground 4～5 minutes, be transferred to valve bag, uncovered 10～12 hours, treat that ether waves most back sealing.And establish adjuvant contrast, and the medicine contrast, medicine mixes with adjuvant 1:1 and does not grind group, with the sample disposal methods.Two parts of each ratio operation repetitives.
1.3 samples weighing
Insert a certain amount of sample (containing medicine 1g) in the weighing botle after constant weight, precision is weighed.Above-mentioned sample is put into pallet, place in the baking oven (40 ℃ of constant temperature, air blast), weighed once record data, the remaining percentage rate of computation model medicine in per 24 hours.With the weighing time be abscissa, medicine residue percentage rate is the vertical coordinate mapping.Weighed record data once in per 24 hours.
2. experimental result
2.1 do not have ether group and ether group sample data relatively, see Figure 15,16.
Conclusion: from Figure 15 and Figure 16 as can be seen, curve is to descend and is linear, distinguishes obviously.Represent with medicine residue percentage rate, evaporable minimum be that medicine/adjuvant is the 1:3 group, maximum is the medicine matched group.Remaining presses the minimizing of the shared percentage ratio of adjuvant and volatile quantity increases.Illustrate that adjuvant has certain Stabilization to Borneolum Syntheticum really.
2.2 the grinding group with do not grind group relatively (1:1), see Figure 17.
Conclusion: as can be seen from Figure 17, no ether group not grinding ratio grinding volatile quantity is slightly little; And the ether group is ground the back volatile quantity less than not grinding; But no significant difference shows that grinding is little to the stability of drug products influence to promoting PVPP.
2.3 each ratio sample does not have ether and the ether contrast is arranged, and sees Figure 18-23.
Result: compare from the ether group and the no ether group of each ratio, find that curve overlaps substantially, illustrate that the adding ether is little to medicine stabilizing influence to increasing adjuvant.The volatile quantity of some ether group is big slightly, and reason may be that volatilization can be taken away a part of Borneolum Syntheticum owing in the medicine remaining ether is arranged, and causes volatile quantity to increase.
Experimental example 4 PVPP are to Borneolum Syntheticum study on the stability (ethanol group)
1. experimental technique
1.1 weighing botle constant weight
Get 24 of weighing botles, numbering is cleaned with distilled water, places clean pallet, 105 ℃ of dryings, and the difference of weighing after the double drying is below 0.3mg; Be dried to constant weight the second time and after each time weigh and carry out after one hour continuing drying under 105 ℃ of rated conditions.
1.2 sample preparation
A group sample is the dehydrated alcohol group, and medicine is a Borneolum Syntheticum, and adjuvant is PVPP, and solvent is a dehydrated alcohol, and establishing medicine and solvent ratios is 1:1,2:1, and 5:1 gets Borneolum Syntheticum and adjuvant by the 1:1 mixed, dropwise adds dehydrated alcohol more according to the above ratio and grinds.Place on the pan paper and spread out, wave most ethanol, put into valve bag and seal.And establish the adjuvant matched group, medicine matched group, not solubilizer grinding group (1:1).Two parts of each ratio operation repetitives.
B group sample is 95% ethanol group, and solvent is 95% ethanol, and establishing medicine and solvent ratios is 1:1,2:1, and 5:1 gets Borneolum Syntheticum and adjuvant by the 1:1 mixed, dropwise adds 95% ethanol more according to the above ratio and grinds.Place on the pan paper and spread out, wave most ethanol, put into valve bag and seal.And establish the adjuvant matched group, medicine matched group, solubilizer grinding group (medicine and adjuvant 1:1) not, starch group (medicine and solvent 2:1; 5:1), lactose group (medicine and solvent 5:1), medicine and adjuvant 1:1.Two parts of each ratio operation repetitives.
1.3 samples weighing
Insert a certain amount of sample (containing medicine 0.5g) in the weighing botle after constant weight, precision is weighed.Above-mentioned sample is put into pallet, place in the baking oven (40 ℃ of constant temperature, air blast), weighed once record data, the remaining percentage rate of computation model medicine in per 24 hours.With the weighing time be abscissa, medicine residue percentage rate is the vertical coordinate mapping.Weighed record data once in per 24 hours.
2. experimental result
2.1 with the dehydrated alcohol is each ratio data contrast of sample of solvent, sees Figure 24.
The result: as can be seen from Figure 24, when making solvent with dehydrated alcohol, each ratio, medicine residue percentage ratio is higher than 5:1 when 1:1 and 2:1, more helps the Stabilization of adjuvant to medicine when showing the dehydrated alcohol large percentage.And the difference of 1:1 and 2:1 is little, and expansion reaches maximum to solvent to adjuvant in the time of may being medicine and solvent ratios 2:1, so the two difference is little.
2.2 with 95% ethanol is each ratio data contrast of sample of solvent, sees Figure 25.
The result: as can be seen from Figure 25, when making solvent with 95% ethanol, each ratio, medicine residue percentage ratio is a little more than 5:1 when 1:1 and 2:1, but difference is not obvious.
2.3 each ratio data of dehydrated alcohol group and 95% ethanol group sample relatively, sees Figure 26.
Conclusion: as can be seen from the figure, be solvent 1:1 with the dehydrated alcohol, 2:1 stability is higher than 95% ethanol in proportion, and 5:1 then the two difference is little.Show that dehydrated alcohol makes solvent and can promote PVPP to the stability of drug effect, this facilitation is better than 95% ethanol.Use the solvent of 2:1 ratio bigger to the stability promotion, 5:1 then influences less, may be because the solvent use amount is less, thereby failing fully to contact with medicine and adjuvant plays a role.
2.4 different auxiliary material (lactose, starch), Figure 27 is seen in the sample data contrast of distinct methods (solubilizer, dry grinding).
The result: as can be seen from Figure 27, as adjuvant, it is the adjuvant group that medicine residue percentage rate is lower than with PVPP with lactose, starch, shows that not only there is physically the effect of covering in PVPP to medicine, also has certain absorption.Dry grinding group medicine residue percentage rate is lower than the solubilizer group, shows that adding solvent in process of lapping can promote PVPP to the stability of drug effect.
Description of drawings
Fig. 1: PVPP is to the study on the stability (air blast, no ether) of Mentholum;
Fig. 2: PVPP is to the study on the stability (air blast, ether) of Mentholum;
Fig. 3: the grinding group with do not grind group relatively (1:1);
Fig. 4: ether group and grinding group be (medicine and adjuvant 1:3) relatively;
Fig. 5: ether group and grinding group be (medicine and adjuvant 1:2) relatively;
Fig. 6: ether group and grinding group be (medicine and adjuvant 1:1) relatively;
Fig. 7: ether group and grinding group be (medicine and adjuvant 2:1) relatively;
Fig. 8: ether group and grinding group be (medicine and adjuvant 3:1) relatively;
Fig. 9: ether group and grinding group be (medicine and adjuvant 4:1) relatively;
Figure 10: PVPP is to the study on the stability (ethanol) of Mentholum;
Figure 11: PVPP is to the study on the stability (dehydrated alcohol) of Mentholum;
Figure 12: PVPP is to the study on the stability (95% ethanol) of Mentholum;
Figure 13: PVPP is to the study on the stability (two kinds of concentration ethanol relatively) of Mentholum;
Figure 14: PVPP is to the study on the stability (starch, dry grinding contrast) of Mentholum;
Figure 15: PVPP is to the study on the stability (air blast, no ether) of Borneolum Syntheticum;
Figure 16: PVPP is to the study on the stability (air blast, ether) of Borneolum Syntheticum;
Figure 17: the grinding group with do not grind group relatively (1:1);
Figure 18: ether group and grinding group be (medicine and adjuvant 1:3) relatively;
Figure 19: ether group and grinding group be (medicine and adjuvant 1:2) relatively;
Figure 20: ether group and grinding group be (medicine and adjuvant 1:1) relatively;
Figure 21: ether group and grinding group be (medicine and adjuvant 2:1) relatively;
Figure 22: ether group and grinding group be (medicine and adjuvant 3:1) relatively;
Figure 23: ether group and grinding group be (medicine and adjuvant 4:1) relatively;
Figure 24: PVPP is to the study on the stability (dehydrated alcohol) of Borneolum Syntheticum;
Figure 25: PVPP is to the study on the stability (95% ethanol) of Borneolum Syntheticum;
Figure 26: PVPP is to the study on the stability (solvent contrast) of Borneolum Syntheticum;
Figure 27: PVPP is to the study on the stability (adjuvant contrast) of Borneolum Syntheticum.
The present invention investigates PVPP to the impact of volatile medicine stability, in the hope of enlarging pharmaceutic adjuvant PVPP Range of application, and better in the Chinese medicine modern formulation, preserve volatile ingredient for how reference be provided Foundation. By in experiment, choose borneol, Mentholum is model drug, take PVPP as research auxiliary material, Take medicine residue percentage as Comparative indices, take the constant temperature weight method, examination medicine and auxiliary material different proportion The method of reaching is mixed the impact to volatile medicine stability, and analyzes possible related causes. Experiment showed, Under experiment condition, PVPP can reduce the volatile quantity of model drug borneol and Mentholum, and takes one Fixed mixed method and the suitable solvent of adding can promote this effect. Therefore reach a conclusion PVPP Can strengthen the stability of volatile medicine.
Following examples are used for further specifying but are not limited to the present invention.
The specific embodiment
Embodiment 1:
Add polyvinylpolypyrrolidone in the enclose process of the medicine that contains Mentholum, the ratio of Mentholum and polyvinylpolypyrrolidone is: 4:1; In the enclose process, grind; Add the organic solvent dehydrated alcohol, the ratio of Mentholum and dehydrated alcohol is: 2:1, make tablet according to common process.
Embodiment 2:
Add polyvinylpolypyrrolidone in the enclose process of the medicine that contains Borneolum Syntheticum, the ratio of Borneolum Syntheticum and polyvinylpolypyrrolidone is: 3:1; In the enclose process, grind; Add the organic solvent ether, the ratio of Borneolum Syntheticum and ether is: 1:1, make capsule according to common process.
Embodiment 3:
Add polyvinylpolypyrrolidone in the enclose process of the medicine that contains Rhizoma Chuanxiong volatile oil, the ratio of Rhizoma Chuanxiong volatile oil and polyvinylpolypyrrolidone is: 2:1; In the enclose process, grind; Add the organic solvent ether, the ratio of Rhizoma Chuanxiong volatile oil and ether is: 1:1, make granule according to common process.
Embodiment 4:
Add polyvinylpolypyrrolidone in the enclose process of the medicine that contains Folium Perillae volatile oil, the ratio of Folium Perillae volatile oil and polyvinylpolypyrrolidone is: 1:2; In the enclose process, grind; Add organic solvent 95% ethanol, Folium Perillae volatile oil and 95% alcoholic acid ratio are: 5:1, make pill according to common process.
Embodiment 5:
Add polyvinylpolypyrrolidone in the enclose process of the medicine that contains Radix Angelicae Sinensis volatile oil, the ratio of Radix Angelicae Sinensis volatile oil and polyvinylpolypyrrolidone is: 1:3; In the enclose process, grind; Add the organic solvent dehydrated alcohol, the ratio of Radix Angelicae Sinensis volatile oil and dehydrated alcohol is: 2:1, make powder according to common process.
Embodiment 6:
Add polyvinylpolypyrrolidone in the enclose process of the medicine that contains Oleum menthae, the ratio of Oleum menthae and polyvinylpolypyrrolidone is: 1:4; In the enclose process, grind; Add the organic solvent ether, the ratio of Oleum menthae and ether is: 1:1, make tablet according to common process.
Embodiment 7:
Add polyvinylpolypyrrolidone in the enclose process of the medicine of the miscella that contains Oleum menthae, Rhizoma Chuanxiong volatile oil, Folium Perillae volatile oil and the above-mentioned four kinds of volatile oil of Radix Angelicae Sinensis volatile oil, the ratio of miscella and polyvinylpolypyrrolidone is: 3:1; In the enclose process, grind; Add organic solvent 95% ethanol, miscella and 95% alcoholic acid ratio are: 2:1, make tablet according to common process.
Claims (9)
1, a kind of inclusion method that contains the medicine of volatile ingredient is characterized in that containing in the enclose process in the medicine of volatile ingredient and adds polyvinylpolypyrrolidone.
2, inclusion method as claimed in claim 1 is characterized in that containing the medicine of volatile ingredient and the ratio of polyvinylpolypyrrolidone is: 4:1,3:1,2:1,1:1,1:2,1:3,1:4,1:5,1:6,1:7 or 1:8.
3, as the arbitrary described inclusion method of claim 1-2, it is characterized in that in the enclose process, grinding.
4, inclusion method as claimed in claim 3 is characterized in that adding conventional organic solvent in the enclose process.
5, inclusion method as claimed in claim 4 is characterized in that the ratio of medicine and organic solvent is: 2:1,1:1 or 5:1.
6,, it is characterized in that organic solvent is meant dehydrated alcohol, ether or 95% ethanol as claim 4 or 5 arbitrary described inclusion methods.
7,, it is characterized in that the wherein said medicine that contains volatile ingredient is meant Mentholum or Borneolum Syntheticum as claim 1,2,4 or 5 arbitrary described inclusion methods.
8, inclusion method as claimed in claim 3 is characterized in that the wherein said medicine that contains volatile ingredient is meant Mentholum or Borneolum Syntheticum.
9, inclusion method as claimed in claim 6 is characterized in that the wherein said medicine that contains volatile ingredient is meant Mentholum or Borneolum Syntheticum.
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| WO2020012761A1 (en) * | 2018-07-12 | 2020-01-16 | 株式会社 東亜産業 | Filler for fragrance cartridge, aerosol-forming base material for fragrance cartridge having same, and fragrance cartridge having same |
| WO2020013339A1 (en) * | 2018-07-12 | 2020-01-16 | 株式会社 東亜産業 | Heated fragrance-emitting base material applied to fragrance cartridge, heated fragrance-emitting substrate, fragrance cartridge comprising heated fragrance-emitting substrate, and method and apparatus for manufacturing heated fragrance-emitting substrate |
| JP2020014455A (en) * | 2018-07-12 | 2020-01-30 | 株式会社 東亜産業 | Filling material for aromatic cartridge, aerosol formation substrate for aromatic cartridge having the same, and aromatic cartridge having the same |
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