CN1748698A - Albendazole new form for treating chronic nasosinusitis - Google Patents
Albendazole new form for treating chronic nasosinusitis Download PDFInfo
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- CN1748698A CN1748698A CN 200410078472 CN200410078472A CN1748698A CN 1748698 A CN1748698 A CN 1748698A CN 200410078472 CN200410078472 CN 200410078472 CN 200410078472 A CN200410078472 A CN 200410078472A CN 1748698 A CN1748698 A CN 1748698A
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- Prior art keywords
- albendazole
- nasal
- spray
- aerosol
- sinusitis
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- HXHWSAZORRCQMX-UHFFFAOYSA-N albendazole Chemical compound CCCSC1=CC=C2NC(NC(=O)OC)=NC2=C1 HXHWSAZORRCQMX-UHFFFAOYSA-N 0.000 title claims abstract description 43
- 229960002669 albendazole Drugs 0.000 title claims abstract description 43
- 230000001684 chronic effect Effects 0.000 title abstract description 4
- 239000000443 aerosol Substances 0.000 claims abstract description 10
- 206010009137 Chronic sinusitis Diseases 0.000 claims description 18
- 208000027157 chronic rhinosinusitis Diseases 0.000 claims description 16
- 239000007923 nasal drop Substances 0.000 claims description 16
- 229940098458 powder spray Drugs 0.000 claims description 14
- 239000007921 spray Substances 0.000 claims description 11
- 210000003928 nasal cavity Anatomy 0.000 claims description 10
- 239000002552 dosage form Substances 0.000 claims description 4
- 239000004615 ingredient Substances 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 abstract description 6
- 239000000843 powder Substances 0.000 abstract description 3
- 241000475481 Nebula Species 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 238000005507 spraying Methods 0.000 abstract 1
- 239000007922 nasal spray Substances 0.000 description 17
- 239000003814 drug Substances 0.000 description 15
- 210000003695 paranasal sinus Anatomy 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 208000000592 Nasal Polyps Diseases 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 208000016366 nasal cavity polyp Diseases 0.000 description 5
- 201000009890 sinusitis Diseases 0.000 description 5
- 206010019233 Headaches Diseases 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 206010028748 Nasal obstruction Diseases 0.000 description 4
- 231100000869 headache Toxicity 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 201000007100 Pharyngitis Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 206010044302 Tracheitis Diseases 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000003203 everyday effect Effects 0.000 description 3
- 230000036285 pathological change Effects 0.000 description 3
- 231100000915 pathological change Toxicity 0.000 description 3
- 206010039083 rhinitis Diseases 0.000 description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- VXTGHWHFYNYFFV-UHFFFAOYSA-N albendazole S-oxide Chemical compound CCCS(=O)C1=CC=C2NC(NC(=O)OC)=NC2=C1 VXTGHWHFYNYFFV-UHFFFAOYSA-N 0.000 description 2
- 229950010075 albendazole sulfoxide Drugs 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 206010006451 bronchitis Diseases 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000000749 insecticidal effect Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000004086 maxillary sinus Anatomy 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- OXFSTTJBVAAALW-UHFFFAOYSA-N 1,3-dihydroimidazole-2-thione Chemical class SC1=NC=CN1 OXFSTTJBVAAALW-UHFFFAOYSA-N 0.000 description 1
- KTPMVZCGIJJWCD-UHFFFAOYSA-N 1-hydroxypyridin-2-imine Chemical compound ON1C=CC=CC1=N KTPMVZCGIJJWCD-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- 206010011878 Deafness Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 208000032984 Intraoperative Complications Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 206010039101 Rhinorrhoea Diseases 0.000 description 1
- 208000009205 Tinnitus Diseases 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000000507 anthelmentic effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 210000005098 blood-cerebrospinal fluid barrier Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000006013 carbendazim Substances 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 208000013804 chronic ethmoidal sinusitis Diseases 0.000 description 1
- 201000010761 chronic ethmoiditis Diseases 0.000 description 1
- 201000006918 chronic maxillary sinusitis Diseases 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 231100000895 deafness Toxicity 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 238000013129 endoscopic sinus surgery Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960002179 ephedrine Drugs 0.000 description 1
- 201000009320 ethmoid sinusitis Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 201000006916 frontal sinusitis Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 208000016354 hearing loss disease Diseases 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000002262 irrigation Effects 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 201000008836 maxillary sinusitis Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 208000010753 nasal discharge Diseases 0.000 description 1
- 210000002850 nasal mucosa Anatomy 0.000 description 1
- 210000000492 nasalseptum Anatomy 0.000 description 1
- 230000003448 neutrophilic effect Effects 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000886 tinnitus Toxicity 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 210000001944 turbinate Anatomy 0.000 description 1
Abstract
The present invention relates to the preparation process of nebula, aerosol, powder spraying agent and nose drop of albendazole and their application in treating chronic nasosinusitis.
Description
The present invention relates to use albendazole to prepare spray, aerosol, powder spray and nasal drop, and these contain spray, aerosol, powder spray and the nasal drop application in the treatment chronic sinusitis of albendazole.
One, chronic sinusitis brief introduction
Chronic sinusitis generally promptly refers to chronic purulent sinusitis, is nasal sinuses mucosa chronic suppurative inflammation, and is wherein maximum with chronic maxillary sinusitis, and normal and chronic ethmoidal sinusitis merges and exists, and how to be treated delay timely and reasonably because of acute purulent nasosinusitis and causes.Infection, allergic rhinitis also are its main causes.In recent years, the pathological changes of nasal meatus complex causes that nasal sinuses drain obstacle is caused extensive attention, and has therefore carried out the sinusitis operation under the functional nasal endoscope.
1, cardinal symptom is: pus tears, nasal obstruction, headache (often show as dull pain or head sense of heaviness, daytime is heavy, and night is light), abundant expectoration, foreign body sensation or dry pharynx pain etc., sometimes tinnitus, deafness can be arranged, the course of disease surpasses 6-8 week, if the course of disease is shorter, may be acute or subacute sinusitis.
2, general treatment comprises furacilin-ephedrine solution collunarium, antibiotics and puncture and irrigation of maxillary sinus etc.
If 3 general treatment effects are not good enough.Should carry out nasal cavity inspection or nasal sinuses CT examination under the detailed conchoscope, main understanding has or not the pathological changes that influences the nasal sinuses drain.The CT in left side takes the photograph the inflammation that sheet shows the bilateral maxillary sinus, and has liquid flat.
4, operative treatment comprises and removes the operation that removes the cause of disease, (as the capable nasal septal construction of high-order deviation of nasal septum; To the middle nasal concha that hypertrophy or polypoid become, feasible partial middle turbinectomy is if there is nasal polyp then to go nasal polypectomy), radical maxillary sinusotomy.
5, more popular at present operation method is a functional endoscopic sinus surgery.The method surgical injury is little, meets The normal anatomic and physiological, and effect is better.As might go this operation as far as possible
Two, albendazole brief introduction
Albendazole, english common name are Albendazole; Generic name is: Albendazole, Albendazole, 5-rosickyite-2-Carbendazim, rosickyite reach azoles, the third mercapto imidazoles, albendazole etc.Be broad-spectrum de-worming medicine.Can influence the multiple biochemical metabolism approach of polypide.This medicine can suppress the picked-up of Enterozoa to glucose, causes the intravital glycogen depletion of worm; Also can combine and suppress micropipe aggregation with the polypide tubulin, thus transhipment of secretion inhibitor granule and the motion of other subcellular organelle; Also can suppress polypide mitochondrion fumaric reductase system, reduce ATP and generate, thereby disturb polypide existence and breeding and cause its death.This medicine is the high-efficiency broad spectrum anthelmintic, is the strongest a kind of of insecticidal action in the benzimidazole medicine.Oral absorption is slow.The 2.5-3 hour blood drug level peaking in oral back, 15mg/kg on the one are at twice or divide three oral area under curve that reach (AUC) identical.This medicine bioavailability is distributed in liver, kidney, muscle in vivo and can sees through blood-cerebrospinal fluid barrier, so finite concentration is also arranged in the cerebral tissue less than 5%.This medicine is converted into Albendazole-sulfoxide and Albendazole-sulfone in liver, the former is an insecticidal constituent.Former medicine and the sulfone derivative concentration in blood is extremely low, can not measure, and the concentration change of Albendazole-sulfoxide is very big, does not wait from 0.04 μ g/mL to 0.55 μ g/mL, average 0.16 μ g/mL.Former medicine and metabolite thereof had 87% with homaluria in 24 hours, the kidney clearance rate is 0.16-0.81L/h, and 13% drains through digestive tract.Half-life is 8.5-10.5 hour.Medicine does not have depot action in vivo.Do not removed by hemodialysis.
Three, so far, all do not see any report or document record that albendazole is used for the treatment of chronic sinusitis both at home and abroad as yet.
The present invention is made into compound recipe with albendazole as independent effective ingredient or with other medicines, makes the dosage form of nasal-cavity administration, and these dosage forms include, but are not limited to: nasal drop, spray, aerosol and powder spray.
Indication with albendazole or the nasal drop made from the compound recipe that contains albendazole, spray, aerosol and powder spray of the present invention, include, but are not limited to following disease: chronic sinusitis, nasal polyp or nasal polyp, rhinitis, pharyngitis, tracheitis and bronchitis.
Use of the present inventionly with albendazole or the nasal drop made from the compound recipe that contains albendazole, spray, aerosol and powder spray, for the chronic sinusitis patient, directly nasal-cavity administration can be alleviated relevant symptom effectively.
Nasal drop of the present invention, spray, aerosol and powder spray all meet the definition of the Pharmacopoeia of the People's Republic of China (version was two ones in 2000) about nasal drop, spray, aerosol and powder spray.
Chronic sinusitis of the present invention is that those skilled in the art is known, has it to define accurately in the modern medical book.Its pathological change as previously mentioned.Rhinitis of the present invention, pharyngitis, tracheitis and bronchitis also are that the ordinary artisan of this area is known, have it to define accurately in the modern medical book.
By the preparation of following examples, and be described with the application of albendazole nasal drop, spray, aerosol and powder spray treatment chronic sinusitis to albendazole nasal drop of the present invention, spray, aerosol and powder spray.It should be noted that, following embodiment just is used for explanation and unrestricted the present invention, well-known to those skilled in the artly by other administration route albendazole is used for the treatment of nasal polyp or nasal polyp, rhinitis, pharyngitis, tracheitis and bronchitic technology all within the scope of the invention.
The preparation of embodiment 1 albendazole nasal mist
In ten thousand grades of environment, albendazole is dissolved in normal saline, be prepared into the solution of 1mg/ml, add geramine, the concentration that makes geramine is 0.02%.In the nasal mist bottle, the spray valve of screwing on promptly gets the albendazole nasal mist with this liquid medicine filling.
The preparation of embodiment 2 albendazole nasal aerosol
In ten thousand grades of environment, albendazole is dissolved in normal saline, be prepared into the solution of 1mg/ml, add geramine, the concentration that makes geramine is 0.02%.This liquid medicine filling in the nasal aerosol bottle, is added propellant, load onto aerosol valve, promptly get the albendazole nasal aerosol.
The preparation of embodiment 3 albendazole nasal cavity powder sprays
In ten thousand grades of environment, with albendazole 20mg, hydroxypropyl cellulose (HPC) 980mg, Benasept 0.1mg co-blended, the albendazole that obtains homogeneous is the powder body of 1 μ g/mg, and diameter of particle should be 30～150 μ m, be filled in the hard capsule, get nasal-cavity administration albendazole powder spray.Per nasal sprays into administration with the dust cloud device during use.
The preparation of embodiment 4 albendazole nasal drop
In ten thousand grades of environment, albendazole is dissolved in normal saline, be prepared into the solution of 1mg/ml, add geramine, the concentration that makes geramine is 0.02%.This liquid medicine filling in the nasal drop bottle, is promptly got the albendazole nasal drop.
Embodiment 5 uses albendazole nasal mist treatment chronic sinusitis
Among the 10 routine patients, male 5 examples, women 5 examples; 15～43 years old age; Course of disease April～1 year.Maxillary sinusitis 3 examples wherein, frontal sinusitis 4 examples, ethmoiditis 3 examples.Symptom all has nasal obstruction, stream turbid nasal discharge, headache, or fear of cold, heating are arranged, symptom such as feel sick.Department of eye is checked: the nasal mucosa congestion and edema, nasal cavity has purulent secretion.The X line is taken the photograph sheet: the increase in density of hole chamber, acute stage total white blood cells and neutrophilic granulocyte raise.
Therapeutic Method: use albendazole nasal mist spray nose secondary every day, continue January.
Result: cure (transference cure, it is no abnormal that X line nasal sinuses is taken the photograph sheet) 2 examples, (symptom is obviously improved, and nasal cavity checks that mucous hyperemia swelling alleviates, and X line nasal sinuses is taken the photograph sheet and obviously improved) 6 examples that take a turn for the better, invalid (interruption of taking medicine) 2 examples.All case was followed up a case by regular visits to 6 months, and half a year is recidivist's 9 examples not.
Embodiment 6 uses albendazole nasal aerosol treatment chronic sinusitis
Repeat " embodiment 1 " described experiment, what adopt except that curative is that patient's state of an illness of hydrochloric acid albendazole nasal aerosol and observation is with quantity is different, patient goes into group standard, therapeutic scheme, curative effect judging standard all with " embodiment 1 ", and experimental result is similar with " embodiment 1 ".
Embodiment 7 uses albendazole nasal cavity powder spray treatment chronic sinusitis
44 years old women is diagnosed as chronic sinusitis, and with the treatment of hydrochloric acid albendazole nasal cavity powder spray, be administered once every day, continues 15 days, and symptom is obviously improved.
Embodiment 8 uses albendazole nasal drop treatment chronic sinusitis
An adult female, pus tears, nasal obstruction, headache are diagnosed as chronic sinusitis, and with " embodiment 7 " described phosphoric acid albendazole nasal drop treatment, every day, secondary continued 25 days, and nasal obstruction, headache are obviously alleviated, and the pus tears reduce.
Claims (2)
1. the dosage form of the nasal-cavity administration that albendazole is made as effective ingredient, these dosage forms comprise:
1. nasal drop;
2. spray;
3. aerosol;
4. powder spray.
2. the application of albendazole in the production of the nasal drop that is used as the treatment chronic sinusitis, spray, aerosol, powder spray.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410078472 CN1748698A (en) | 2004-09-14 | 2004-09-14 | Albendazole new form for treating chronic nasosinusitis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410078472 CN1748698A (en) | 2004-09-14 | 2004-09-14 | Albendazole new form for treating chronic nasosinusitis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1748698A true CN1748698A (en) | 2006-03-22 |
Family
ID=36604477
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410078472 Pending CN1748698A (en) | 2004-09-14 | 2004-09-14 | Albendazole new form for treating chronic nasosinusitis |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1748698A (en) |
-
2004
- 2004-09-14 CN CN 200410078472 patent/CN1748698A/en active Pending
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| C06 | Publication | ||
| PB01 | Publication | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20070309 Address after: No. 12, Huayuan Road, Jiangsu, Nanjing Applicant after: Jiangsu Simcere Pharmaceutical Research Company Limited Address before: 5C, building six, 6 District, far road, century garden, Beijing, Haidian District Applicant before: Wang Heyao Co-applicant before: Zheng Wenjie |
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| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |