CN1568947A - Bromhexine Hydrochloride drop pills and preparation method thereof - Google Patents
Bromhexine Hydrochloride drop pills and preparation method thereof Download PDFInfo
- Publication number
- CN1568947A CN1568947A CN 200410044435 CN200410044435A CN1568947A CN 1568947 A CN1568947 A CN 1568947A CN 200410044435 CN200410044435 CN 200410044435 CN 200410044435 A CN200410044435 A CN 200410044435A CN 1568947 A CN1568947 A CN 1568947A
- Authority
- CN
- China
- Prior art keywords
- bromhexine hydrochloride
- preparation
- coolant
- polyethylene glycol
- bromhexine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 229960002335 bromhexine hydrochloride Drugs 0.000 title claims abstract description 30
- YRSGDLIATOURQO-UHFFFAOYSA-N ethyl 4-acetyl-5-oxohexanoate Chemical compound CCOC(=O)CCC(C(C)=O)C(C)=O YRSGDLIATOURQO-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 239000006187 pill Substances 0.000 title claims abstract description 17
- 238000002360 preparation method Methods 0.000 title claims description 13
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 12
- 239000002826 coolant Substances 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 8
- 229940093429 polyethylene glycol 6000 Drugs 0.000 claims description 8
- 239000000843 powder Substances 0.000 claims description 8
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 6
- 229940008099 dimethicone Drugs 0.000 claims description 6
- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims description 6
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 6
- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 claims description 6
- 229960000502 poloxamer Drugs 0.000 claims description 6
- 229920001983 poloxamer Polymers 0.000 claims description 6
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 6
- 239000000758 substrate Substances 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 4
- 239000011159 matrix material Substances 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- IQXJCCZJOIKIAD-UHFFFAOYSA-N 1-(2-methoxyethoxy)hexadecane Chemical compound CCCCCCCCCCCCCCCCOCCOC IQXJCCZJOIKIAD-UHFFFAOYSA-N 0.000 claims description 2
- 239000001828 Gelatine Substances 0.000 claims description 2
- 241000238631 Hexapoda Species 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- 229950009789 cetomacrogol 1000 Drugs 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 claims description 2
- 235000011187 glycerol Nutrition 0.000 claims description 2
- 229960005150 glycerol Drugs 0.000 claims description 2
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 claims description 2
- 229940057995 liquid paraffin Drugs 0.000 claims description 2
- -1 liquid paraffin Substances 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 229940093430 polyethylene glycol 1500 Drugs 0.000 claims description 2
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 claims description 2
- 229940080350 sodium stearate Drugs 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 claims description 2
- 239000008158 vegetable oil Substances 0.000 claims description 2
- 239000001993 wax Substances 0.000 claims description 2
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 12
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 208000019505 Deglutition disease Diseases 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 2
- 239000002671 adjuvant Substances 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 238000004090 dissolution Methods 0.000 description 19
- 238000001514 detection method Methods 0.000 description 6
- 230000003419 expectorant effect Effects 0.000 description 4
- 229940075507 glyceryl monostearate Drugs 0.000 description 4
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 206010036790 Productive cough Diseases 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000003172 expectorant agent Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000004891 communication Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 208000024794 sputum Diseases 0.000 description 2
- 210000003802 sputum Anatomy 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- UMGHSLADWDJYEG-UHFFFAOYSA-N Cl.CN.CN(C1=CC=C(C=C1Br)Br)C1CCCCC1 Chemical group Cl.CN.CN(C1=CC=C(C=C1Br)Br)C1CCCCC1 UMGHSLADWDJYEG-UHFFFAOYSA-N 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 206010062717 Increased upper airway secretion Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 210000002175 goblet cell Anatomy 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 208000026435 phlegm Diseases 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses a bromhexine hydrochloride drop pill prepared through ultramicro disintegration and drop pills manufacturing technique, which has the advantages of improving collapse and dissolving speed, dissolving out speed and degree, quick effect, increased medicament stability, reduced adjuvant consumption, lowered production costs, and easiness in carrying and use, oral or swallow administration, it has good compliance, thus is especially suitable for children, the elderly, bedridden patients and dysphagia patients.
Description
Technical field
The present invention relates to a kind of pharmaceutical product and preparation method thereof, specifically bromhexine hydrochloride drop pill and preparation method thereof.
Background technology
Bromhexine hydrochloride has stronger dissolving to glue the expectorant effect, can make the plain cracking of polysaccharide fiber of apoplexy due to phlegm, and the desaturation sputum suppresses the synthetic glycoprotein of goblet cell and mucus body of gland sputum acid is reduced, and lowers expectorant viscosity, is convenient to discharge.
Bromhexine hydrochloride is fast and complete from gastrointestinal absorption, 1 hour blood drug level peaking after the oral absorption.The metabolite of the overwhelming majority is discharged with urine, and feces is only discharged minimum part.The oral formulations of list marketing at present only has tablet, clinically is used for the treatment of as expectorant that expectorant such as chronic bronchitis, asthma are sticking to be difficult for expectoration and to cause patient out of breath.
The bromhexine hydrochloride odorless, tasteless, soluble,very slightly in water, its disintegration of tablet time is long, and dissolution and dissolution rate are low, absorption difference, bioavailability is low, and the supplementary product consumption ratio is big, and child, old people, bed patient and dysphagia patients are taken inconvenience, compliance is poor, has influenced the performance of bromhexine hydrochloride therapeutical effect.
The present invention makes the bromhexine hydrochloride drop pill by using ultramicro communication technique and dropping pill formulation Technology exactly, thereby overcomes the above defective of bromhexine hydrochloride sheet, and the therapeutical effect of bromhexine hydrochloride is given full play to.
Summary of the invention
The bromhexine hydrochloride drop pill of making by using ultramicro communication technique and dropping pill formulation Technology not only have disintegrate molten loose fast, dissolution and dissolution rate improve, steady quality, the pill volume is little, both can swallow also can buccal, easy to carry and use, onset is rapid, compliance is good, be particularly suitable for the characteristics that child, old people, bed patient and dysphagia patients are taken, but also have working condition and production equipment is simple, production cost is low, compare the advantage that supplementary product consumption reduces with tablet, demonstrated fully the new drug research exploitation spirit that people-oriented.
For achieving the above object, the present invention by the following technical solutions: the bromhexine hydrochloride fine powder of 1 weight portion through micronizing is added in 1～10 weight portion molten matrix, abundant mixing, dropping preparation method is condensed into ball in coolant, remove coolant, drying, promptly.
The chemical name of bromhexine hydrochloride is N-methyl-N-cyclohexyl-2-amino-3.5-dibromobenzene methylamine hydrochloride among the present invention, and structural formula is,
HCl, molecular formula is C
14H
20Br
2N
2.Hcl, molecular weight is 412.60.
Substrate among the present invention includes but not limited to polyethylene glycol 6000, Macrogol 4000, polyethylene glycol 1500, cetomacrogol 1000, sodium stearate, glycerin gelatine, poloxamer, stearic acid, glycerol monostearate acid, insect wax etc.
Coolant among the present invention includes but not limited to dimethicone, liquid paraffin, vegetable oil, water, alcoholic solution etc.
Below through detecting to beneficial effect of the present invention as directed
One, detects index and method
1. disintegrate (molten loosing) time limit: check according to inspection technique disintegration (two appendix XA of Chinese Pharmacopoeia version in 2000).
2. dissolution rate: sample thief, according to dissolution method (two appendix XC first methods of Chinese Pharmacopoeia version in 2000), 900ml is a solvent with hydrochloric acid solution (9 → 1000), and rotating speed is that per minute 100 changes, operation in accordance with the law, in the time of 10,20,30,40 minutes, get solution 10ml, filter, get subsequent filtrate, according to spectrophotography (two appendix IVA of Chinese Pharmacopoeia version in 2000), measure trap at the wavelength place of 249nm, press C
14H
20Br
2N
2Absorptance (the E of Hcl
1cm 1%) be 270 calculating stripping quantities.
Two, commercially available bromhexine hydrochloride sheet testing result
1. disintegration time: 63 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 21.4 38.7 53.2 76.5
Three, example 1 sample detection result
1. the molten diffusing time: 2 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 55.7 86.4 99.8 98.9
Four, example 2 sample detection results
1. the molten diffusing time: 3 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 51.2 89.5 96.7 98.3
Five, example 3 sample detection results
1. the molten diffusing time: 3 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 49.4 87.5 98.6 100.3
Six, example 4 sample detection results
1. the molten diffusing time: 4 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 39.8 79.6 95.3 98.7
Seven, example 5 sample detection results
1. the molten diffusing time: 5 minutes
2. dissolution rate:
Time (minute) 10 20 30 40
Dissolution (%) 43.5 81.4 93.2 96.0
Eight, example 6 sample detection results
1. the molten diffusing time: 6 minutes
2. dissolution rate
Time (minute) 10 20 30 40
Dissolution (%) 43.3 86.5 95.4 98.7
The specific embodiment
One, example 1
Prescription:
Bromhexine hydrochloride 8g
Polyethylene glycol 6000 12g
Make 1000
Method for making: the bromhexine hydrochloride fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves is added in the fused polyethylene glycol 6000 substrate, stirs evenly, and with the dimethicone coolant, the dropping preparation method pill, drying, promptly.
Two, example 2
Prescription:
Bromhexine hydrochloride 8g
Macrogol 4000 12g
Make 1000
Method for making: the bromhexine hydrochloride fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves is added in the fused Macrogol 4000 substrate, stirs evenly, and with the dimethicone coolant, the dropping preparation method pill, drying, promptly.
Three, example 3
Prescription:
Bromhexine hydrochloride 8g
Polyethylene glycol 6000 10g
Macrogol 4000 4g
Make 1000
Method for making: the bromhexine hydrochloride fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves is added in fused Macrogol 4000 and the polyethylene glycol 6000 mixed-matrix, stirs evenly, and with the dimethicone coolant, the dropping preparation method pill, drying, promptly.
Four, example 4
Prescription:
Bromhexine hydrochloride 8g
Glyceryl monostearate 15g
Make 1000
Method for making: the bromhexine hydrochloride fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves is added in the fused glyceryl monostearate substrate, and mixing is a coolant with the frozen water, the dropping preparation method pill, and drying, promptly.
Five, example 5
Prescription:
Bromhexine hydrochloride 8g
Polyethylene glycol 6000 10g
Poloxamer 3g
Make 1000
Method for making: the bromhexine hydrochloride fine powder that the micronizing of learning from else's experience is crossed 200 mesh sieves is added in fused polyethylene glycol 6000 and the poloxamer mixed-matrix, stirs evenly, and with the dimethicone coolant, the dropping preparation method pill, drying, promptly.
Six, example 6
Prescription:
Bromhexine hydrochloride 8g
Glyceryl monostearate 15g
Poloxamer 2g
Make 1000
Method for making: get the mixing fine powders that bromhexine hydrochloride and poloxamer cross 200 mesh sieves through micronizing and be added in the fused glyceryl monostearate substrate, mixing is a coolant with the frozen water, the dropping preparation method pill, and drying, promptly.
Claims (4)
1. bromhexine hydrochloride drop pill and preparation method thereof is characterized in that: the bromhexine hydrochloride fine powder of 1 weight portion through micronizing is added in 1～10 weight portion molten matrix, fully mixing, dropping preparation method is condensed into ball in coolant, remove coolant, drying, promptly.
2. the chemical name of the described bromhexine hydrochloride of claim 1 is N-first-N-cyclohexyl-2-amino-3.5-dibromobenzene methylamine hydrochloride, and structural formula is
Molecular formula is C
14H
20Br
2N
2Hcl, molecular weight are 412.60.
3. the described substrate of claim 1 includes but not limited to polyethylene glycol 6000, Macrogol 4000, polyethylene glycol 1500, cetomacrogol 1000, sodium stearate, glycerin gelatine, poloxamer, stearic acid, glycerol monostearate acid, insect wax etc.
4. the described coolant of claim 1 includes but not limited to dimethicone, liquid paraffin, vegetable oil, water, alcoholic solution etc.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410044435 CN1568947A (en) | 2004-05-13 | 2004-05-13 | Bromhexine Hydrochloride drop pills and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410044435 CN1568947A (en) | 2004-05-13 | 2004-05-13 | Bromhexine Hydrochloride drop pills and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1568947A true CN1568947A (en) | 2005-01-26 |
Family
ID=34481885
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410044435 Pending CN1568947A (en) | 2004-05-13 | 2004-05-13 | Bromhexine Hydrochloride drop pills and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1568947A (en) |
-
2004
- 2004-05-13 CN CN 200410044435 patent/CN1568947A/en active Pending
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |