CN110123756A - A kind of Rupatadine fumarate nasal spray and preparation method thereof - Google Patents
A kind of Rupatadine fumarate nasal spray and preparation method thereof Download PDFInfo
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- CN110123756A CN110123756A CN201910400004.1A CN201910400004A CN110123756A CN 110123756 A CN110123756 A CN 110123756A CN 201910400004 A CN201910400004 A CN 201910400004A CN 110123756 A CN110123756 A CN 110123756A
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- liquid
- nasal spray
- rupatadine fumarate
- rupatadine
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- JYBLCDXVHQWMSU-WLHGVMLRSA-N (e)-but-2-enedioic acid;8-chloro-11-[1-[(5-methylpyridin-3-yl)methyl]piperidin-4-ylidene]-5,6-dihydrobenzo[1,2]cyclohepta[2,4-b]pyridine Chemical compound OC(=O)\C=C\C(O)=O.CC1=CN=CC(CN2CCC(CC2)=C2C3=NC=CC=C3CCC3=CC(Cl)=CC=C32)=C1 JYBLCDXVHQWMSU-WLHGVMLRSA-N 0.000 title claims abstract description 72
- 239000007922 nasal spray Substances 0.000 title claims abstract description 46
- 229940097496 nasal spray Drugs 0.000 title claims abstract description 44
- 238000002360 preparation method Methods 0.000 title claims abstract description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 58
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 50
- 239000008215 water for injection Substances 0.000 claims abstract description 37
- 229920001661 Chitosan Polymers 0.000 claims abstract description 27
- 239000011780 sodium chloride Substances 0.000 claims abstract description 25
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 claims abstract description 24
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 claims abstract description 24
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 claims abstract description 24
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 claims abstract description 24
- 229960005328 rupatadine Drugs 0.000 claims abstract description 16
- WUZYKBABMWJHDL-UHFFFAOYSA-N rupatadine Chemical compound CC1=CN=CC(CN2CCC(CC2)=C2C3=NC=CC=C3CCC3=CC(Cl)=CC=C32)=C1 WUZYKBABMWJHDL-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000007788 liquid Substances 0.000 claims description 102
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 40
- 238000010438 heat treatment Methods 0.000 claims description 28
- 230000001954 sterilising effect Effects 0.000 claims description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- 239000001530 fumaric acid Substances 0.000 claims description 20
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 20
- 239000000243 solution Substances 0.000 claims description 15
- 239000007864 aqueous solution Substances 0.000 claims description 13
- 238000003756 stirring Methods 0.000 claims description 13
- 239000007921 spray Substances 0.000 claims description 12
- 239000012153 distilled water Substances 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 238000004090 dissolution Methods 0.000 claims description 5
- 238000012856 packing Methods 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 2
- 239000008236 heating water Substances 0.000 claims description 2
- 239000006193 liquid solution Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 238000002347 injection Methods 0.000 claims 1
- 239000007924 injection Substances 0.000 claims 1
- 239000003643 water by type Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 10
- 229940079593 drug Drugs 0.000 abstract description 9
- 230000000694 effects Effects 0.000 abstract description 9
- 239000002552 dosage form Substances 0.000 abstract description 5
- 210000001331 nose Anatomy 0.000 description 11
- 241000894006 Bacteria Species 0.000 description 9
- 238000000034 method Methods 0.000 description 3
- 206010039085 Rhinitis allergic Diseases 0.000 description 2
- 201000010105 allergic rhinitis Diseases 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000001932 seasonal effect Effects 0.000 description 2
- QLSJOGIENLKPTF-WLHGVMLRSA-N (e)-but-2-enedioic acid;pyridine Chemical compound C1=CC=NC=C1.OC(=O)\C=C\C(O)=O QLSJOGIENLKPTF-WLHGVMLRSA-N 0.000 description 1
- -1 5- methyl -3- pyridyl Chemical group 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010052140 Eye pruritus Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000001705 Mouth breathing Diseases 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 206010061926 Purulence Diseases 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 229960001803 cetirizine Drugs 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229940088529 claritin Drugs 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000001780 epistaxis Diseases 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 229960003088 loratadine Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 206010041232 sneezing Diseases 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 208000025301 tympanitis Diseases 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0043—Nose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/12—Aerosols; Foams
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Organic Chemistry (AREA)
- Otolaryngology (AREA)
- Dispersion Chemistry (AREA)
- Immunology (AREA)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to biomedicine technical fields more particularly to a kind of Rupatadine fumarate nasal spray and preparation method thereof.Contain Rupatadine fumarate 0.1-0.2 g in terms of Rupatadine in every 1000 mL Rupatadine fumarate nasal spray, chitosan 1-10 g, sodium chloride 4.5-9 g, ethylparaben 0.2-0.5 g, remaining is water for injection.Rupatadine fumarate nasal spray of the invention solves the problems, such as the problem that Present clinical Rupatadine fumarate dosage form is single and Present clinical Rupatadine fumarate tablet oral administration biaavailability is low, and medication is convenient, drug goes directly affected part, good effect, dosage is small, few side effects.
Description
Technical field
The present invention relates to a kind of Rupatadine fumarate nasal sprays and preparation method thereof, belong to field of pharmaceutical preparations.
Background technique
Allergic rhinitis is a kind of common disease of hals,Nasen und Ohrenheilkunde, usually there is a following symptom: itching eyes and being shed tears: nose
Itch, nasal mucus it is more, mostly clear water tears, when infection is purulence tears；Nasal cavity stuffiness, ear muffle, sneezing；Mouth breathing；Smell decline or
It disappears；Giddy headache etc..Following complication can also be caused: insomnia, nasosinusitis, tympanitis, nosebleed.Rupatadine fumarate
Scientific name claims to be the chloro- 6,11- dihydro -11- of 8- [1- [(5- methyl -3- pyridyl group) methyl] -4- perperidylidene] -5H- benzo [5,6]
Cycloheptane simultaneously [1,2-b] pyridine fumarate salt is novel, the potent antiallergic that Uriach drugmaker, Spain develops,
On March 15th, 2003 lists in Spain for the first time, is the tool of tricyclic antidepressants Loratadine of new generation and currently the only listing
There are antihistamine and the only one of blood platelet antagonism activation factor double action strength, colleges and universities' Claritin.This product and chlorine thunder
His fixed, cetirizine etc. is compared, and has better curative effect and smaller side effect, does not find that cardiac toxic and maincenter calmness are made
With the different links that can occur in inflammation inhibit allergy, for treating seasonal and catarrhus perennialis, have non-
Often good industrialization market prospects.
It is domestic at present clinically there was only Rupatadine fumarate piece, for treat seasonal or catarrhus perennialis and
Related indication treatment, therapeutic dosage forms are single, and Rupatadine fumarate piece preparation process is complicated, the auxiliary material shadow that when tabletting is added
The dissolution and bioavilability for ringing Rupatadine, greatly limit its use and curative effect.Rupatadine fumarate nasal spray system
Standby simple, super quality and competitive price, and medication is convenient, drug go directly affected part, and good effect, dosage is small, is to treat perennially and seasonality
The good medicine of allergic rhinitis.
Summary of the invention
The existing dosage form of domestic clinically Rupatadine fumarate administration only has tablet at present, in order to overcome fumaric acid Lu's pa
Defect that he determines that dosage form is single, preparation process is complicated etc. and to play medication convenient, drug go directly affected part, good effect, and dosage is small
Deng advantage, the present invention provides a kind of Rupatadine fumarate nasal sprays and preparation method thereof.
The present invention provides a kind of Rupatadine fumarate nasal spray, every 1000mL fumaric acid Lu Pata in the nasal spray
Determine in nasal spray containing Rupatadine fumarate 0.1-0.2g in terms of Rupatadine, chitosan 1-10g, sodium chloride 4.5-9g, Buddhist nun
Golden ethyl ester 0.2-0.5g is moored, remaining is water for injection.
Further, contain Rupatadine fumarate in every 1000mL Rupatadine fumarate nasal spray in the nasal spray
The 0.15g in terms of Rupatadine, chitosan 5-8g, sodium chloride 6-9g, ethylparaben 0.3g, remaining is water for injection.
Further, the nasal spray is 2mL/ branch.
The present invention also provides a kind of methods of Rupatadine fumarate nasal spray, comprising the following steps: (1) measures rich horse
Chitosan is added in acid solution about 300mL, is sufficiently swollen, and dissolves by heating, is denoted as I liquid；(2) another taking ethylparaben, adds distilled water
50mL is dissolved by heating, i.e. II liquid；(3) about 600mL water for injection separately is taken, adds Rupatadine fumarate, sodium chloride stirring and dissolving, obtains
III liquid.I liquid, II liquid, III liquid are mixed and stirred evenly, IV liquid is obtained.(4) IV liquid is filtered, adds to the full amount of water for injection, stirs from filter
Even, sterilizing dispenses to get Rupatadine fumarate nasal spray.
Further, the fumaric acid solution in the step (1) refers to that concentration is the fumaric acid aqueous solution of 0.5% (w/v).
Its preparation method are as follows: precision weighs fumaric acid 0.5g, is placed in 100mL volumetric flask, is dissolved in water for injection and is diluted to scale,
The fumaric acid aqueous solution for being 0.5% up to concentration.
Further, the heating for dissolving temperature in the step (1) is 60-70 DEG C of heating water bath dissolution.
Further, I liquid in the step (1) refers to form the chitosan gum liquid solution of clear viscous.
Further, the heating for dissolving in the step (2) refers to that dissolution is boiled in heating.
Further, I liquid in the step (3), II liquid, the mixing of III liquid, which refer to, is added to I liquid and II liquid in III liquid,
It is uniformly mixed.
Further, the filtration in the step (4) is using 0.22 μm of miillpore filter.
Further, the sterilizing in the step (4) is gone out 30min in 100 DEG C of flowing steams.
Further, the packing in the step (5) refers under nitrogen flowing, and the solution of sterilizing is propped up sterile point by 2mL/
In sterile spray bottle loaded on the sterilized processing of nose.
Further, the Rupatadine fumarate nasal spray pH in the step (5) is 4.5-5.5.
Rupatadine fumarate nasal spray of the present invention is that low capacity quantifies nasal spray, is had the advantage that
(1) drug absorption is rapid, rapid-action；
(2) bioavilability is high；
(3) medication is convenient, and dosage is accurate；
(4) the through affected part of drug, good effect, dosage is small, few side effects.
Rupatadine fumarate nasal spray of the invention overcomes that Rupatadine fumarate dosage form is single, preparation process is complicated
Defect.
Specific embodiment
Combined with specific embodiments below, the present invention is further clarified.The experiment of actual conditions is not specified in embodiment
Method, usually according to normal condition and condition described in handbook, or according to the normal condition proposed by manufacturer；Used is logical
With equipment, material, reagent etc., it is commercially available unless otherwise specified.
Embodiment 1
Rupatadine fumarate nasal spray prescription (in terms of 500): Rupatadine fumarate (in terms of Rupatadine) 0.1g,
Chitosan 1g, sodium chloride 9g, ethylparaben 0.3g, water for injection add to 1000mL.
Preparation method
(1) chitosan that recipe quantity is added in 0.5% fumaric acid aqueous solution about 300mL is measured, is sufficiently swollen, 60-70 DEG C of water
Bath dissolves by heating, and is denoted as I liquid；
(2) ethylparaben for separately taking recipe quantity, adds distilled water 50mL to boil heating for dissolving, i.e. II liquid；
(3) about 600mL water for injection separately is taken, adds Rupatadine fumarate, the sodium chloride stirring and dissolving of recipe quantity, obtains III
Liquid.I liquid is added in III liquid with II liquid and is uniformly mixed, IV liquid is obtained；
IV liquid is filtered using 0.22 μm of miillpore filter degerming, the 1000mL that adds to the full amount of water for injection is mended from filter, mixes
It is even, 100 DEG C of flowing steams go out 30min sterilizing, under nitrogen flowing, by the solution of sterilizing by 2mL/ branch it is aseptic subpackaged in nose with through going out
In the sterile spray bottle of bacterium processing.
Embodiment 2
Rupatadine fumarate nasal spray prescription (in terms of 500): Rupatadine fumarate (in terms of Rupatadine)
0.15g, chitosan 2g, sodium chloride 9g, ethylparaben 0.3g, water for injection add to 1000mL.
Preparation method
(1) chitosan that recipe quantity is added in 0.5% fumaric acid aqueous solution about 300mL is measured, is sufficiently swollen, 60-70 DEG C of water
Bath dissolves by heating, and is denoted as I liquid；
(2) ethylparaben for separately taking recipe quantity, adds distilled water 50mL to boil heating for dissolving, i.e. II liquid；
(3) about 600mL water for injection separately is taken, adds Rupatadine fumarate, the sodium chloride stirring and dissolving of recipe quantity, obtains III
Liquid.I liquid is added in III liquid with II liquid and is uniformly mixed, IV liquid is obtained；
IV liquid is filtered using 0.22 μm of miillpore filter degerming, the 1000mL that adds to the full amount of water for injection is mended from filter, mixes
It is even, 100 DEG C of flowing steams go out 30min sterilizing, under nitrogen flowing, by the solution of sterilizing by 2mL/ branch it is aseptic subpackaged in nose with through going out
In the sterile spray bottle of bacterium processing.
Embodiment 3
Rupatadine fumarate nasal spray prescription (in terms of 500): Rupatadine fumarate (in terms of Rupatadine) 0.2g,
Chitosan 4g, sodium chloride 9g, ethylparaben 0.3g, water for injection add to 1000mL.
Preparation method
(1) chitosan that recipe quantity is added in 0.5% fumaric acid aqueous solution about 300mL is measured, is sufficiently swollen, 60-70 DEG C of water
Bath dissolves by heating, and is denoted as I liquid；
(2) ethylparaben for separately taking recipe quantity, adds distilled water 50mL to boil heating for dissolving, i.e. II liquid；
(3) about 600mL water for injection separately is taken, adds Rupatadine fumarate, the sodium chloride stirring and dissolving of recipe quantity, obtains III
Liquid.I liquid is added in III liquid with II liquid and is uniformly mixed, IV liquid is obtained；
IV liquid is filtered using 0.22 μm of miillpore filter degerming, the 1000mL that adds to the full amount of water for injection is mended from filter, mixes
It is even, 100 DEG C of flowing steams go out 30min sterilizing, under nitrogen flowing, by the solution of sterilizing by 2mL/ branch it is aseptic subpackaged in nose with through going out
In the sterile spray bottle of bacterium processing.
Embodiment 4
Rupatadine fumarate nasal spray prescription (in terms of 500): Rupatadine fumarate (in terms of Rupatadine) 0.1g,
Chitosan 8g, sodium chloride 8g, ethylparaben 0.3g, water for injection add to 1000mL.
Preparation method
(1) chitosan that recipe quantity is added in 0.5% fumaric acid aqueous solution about 300mL is measured, is sufficiently swollen, 60-70 DEG C of water
Bath dissolves by heating, and is denoted as I liquid；
(2) ethylparaben for separately taking recipe quantity, adds distilled water 50mL to boil heating for dissolving, i.e. II liquid；
(3) about 600mL water for injection separately is taken, adds Rupatadine fumarate, the sodium chloride stirring and dissolving of recipe quantity, obtains III
Liquid.I liquid is added in III liquid with II liquid and is uniformly mixed, IV liquid is obtained；
IV liquid is filtered using 0.22 μm of miillpore filter degerming, the 1000mL that adds to the full amount of water for injection is mended from filter, mixes
It is even, 100 DEG C of flowing steams go out 30min sterilizing, under nitrogen flowing, by the solution of sterilizing by 2mL/ branch it is aseptic subpackaged in nose with through going out
In the sterile spray bottle of bacterium processing.
Embodiment 4
Rupatadine fumarate nasal spray prescription (in terms of 500): Rupatadine fumarate (in terms of Rupatadine) 0.2g,
Chitosan 6g, sodium chloride 6g, ethylparaben 0.3g, water for injection add to 1000mL.
Preparation method
(1) chitosan that recipe quantity is added in 0.5% fumaric acid aqueous solution about 300mL is measured, is sufficiently swollen, 60-70 DEG C of water
Bath dissolves by heating, and is denoted as I liquid；
(2) ethylparaben for separately taking recipe quantity, adds distilled water 50mL to boil heating for dissolving, i.e. II liquid；
(3) about 600mL water for injection separately is taken, adds Rupatadine fumarate, the sodium chloride stirring and dissolving of recipe quantity, obtains III
Liquid.I liquid is added in III liquid with II liquid and is uniformly mixed, IV liquid is obtained；
IV liquid is filtered using 0.22 μm of miillpore filter degerming, the 1000mL that adds to the full amount of water for injection is mended from filter, mixes
It is even, 100 DEG C of flowing steams go out 30min sterilizing, under nitrogen flowing, by the solution of sterilizing by 2mL/ branch it is aseptic subpackaged in nose with through going out
In the sterile spray bottle of bacterium processing.
Embodiment 5
Rupatadine fumarate nasal spray prescription (in terms of 500): Rupatadine fumarate (in terms of Rupatadine) 0.2g,
Chitosan 5g, sodium chloride 7g, ethylparaben 0.3g, water for injection add to 1000mL.
Preparation method
(1) chitosan that recipe quantity is added in 0.5% fumaric acid aqueous solution about 300mL is measured, is sufficiently swollen, 60-70 DEG C of water
Bath dissolves by heating, and is denoted as I liquid；
(2) ethylparaben for separately taking recipe quantity, adds distilled water 50mL to boil heating for dissolving, i.e. II liquid；
(3) about 600mL water for injection separately is taken, adds Rupatadine fumarate, the sodium chloride stirring and dissolving of recipe quantity, obtains III
Liquid.I liquid is added in III liquid with II liquid and is uniformly mixed, IV liquid is obtained；
IV liquid is filtered using 0.22 μm of miillpore filter degerming, the 1000mL that adds to the full amount of water for injection is mended from filter, mixes
It is even, 100 DEG C of flowing steams go out 30min sterilizing, under nitrogen flowing, by the solution of sterilizing by 2mL/ branch it is aseptic subpackaged in nose with through going out
In the sterile spray bottle of bacterium processing.
Embodiment 6
Rupatadine fumarate nasal spray prescription (in terms of 500): Rupatadine fumarate (in terms of Rupatadine) 0.2g,
Chitosan 6g, sodium chloride 6g, ethylparaben 0.3g, water for injection add to 1000mL.
Preparation method
(1) chitosan that recipe quantity is added in 0.5% fumaric acid aqueous solution about 300mL is measured, is sufficiently swollen, 60-70 DEG C of water
Bath dissolves by heating, and is denoted as I liquid；
(2) ethylparaben for separately taking recipe quantity, adds distilled water 50mL to boil heating for dissolving, i.e. II liquid；
(3) about 600mL water for injection separately is taken, adds Rupatadine fumarate, the sodium chloride stirring and dissolving of recipe quantity, obtains III
Liquid.I liquid is added in III liquid with II liquid and is uniformly mixed, IV liquid is obtained；
IV liquid is filtered using 0.22 μm of miillpore filter degerming, the 1000mL that adds to the full amount of water for injection is mended from filter, mixes
It is even, 100 DEG C of flowing steams go out 30min sterilizing, under nitrogen flowing, by the solution of sterilizing by 2mL/ branch it is aseptic subpackaged in nose with through going out
In the sterile spray bottle of bacterium processing.
Embodiment 7
Rupatadine fumarate nasal spray prescription (in terms of 500): Rupatadine fumarate (in terms of Rupatadine)
0.15g, chitosan 3g, sodium chloride 9g, ethylparaben 0.3g, water for injection add to 1000mL.
Preparation method
(1) chitosan that recipe quantity is added in 0.5% fumaric acid aqueous solution about 300mL is measured, is sufficiently swollen, 60-70 DEG C of water
Bath dissolves by heating, and is denoted as I liquid；
(2) ethylparaben for separately taking recipe quantity, adds distilled water 50mL to boil heating for dissolving, i.e. II liquid；
(3) about 600mL water for injection separately is taken, adds Rupatadine fumarate, the sodium chloride stirring and dissolving of recipe quantity, obtains III
Liquid.I liquid is added in III liquid with II liquid and is uniformly mixed, IV liquid is obtained；
IV liquid is filtered using 0.22 μm of miillpore filter degerming, the 1000mL that adds to the full amount of water for injection is mended from filter, mixes
It is even, 100 DEG C of flowing steams go out 30min sterilizing, under nitrogen flowing, by the solution of sterilizing by 2mL/ branch it is aseptic subpackaged in nose with through going out
In the sterile spray bottle of bacterium processing.
Embodiment 8
Rupatadine fumarate nasal spray prescription (in terms of 500): Rupatadine fumarate (in terms of Rupatadine) 0.2g,
Chitosan 4g, sodium chloride 5g, ethylparaben 0.3g, water for injection add to 1000mL.
Preparation method
(1) chitosan that recipe quantity is added in 0.5% fumaric acid aqueous solution about 300mL is measured, is sufficiently swollen, 60-70 DEG C of water
Bath dissolves by heating, and is denoted as I liquid；
(2) ethylparaben for separately taking recipe quantity, adds distilled water 50mL to boil heating for dissolving, i.e. II liquid；
(3) about 600mL water for injection separately is taken, adds Rupatadine fumarate, the sodium chloride stirring and dissolving of recipe quantity, obtains III
Liquid.I liquid is added in III liquid with II liquid and is uniformly mixed, IV liquid is obtained；
IV liquid is filtered using 0.22 μm of miillpore filter degerming, the 1000mL that adds to the full amount of water for injection is mended from filter, mixes
It is even, 100 DEG C of flowing steams go out 30min sterilizing, under nitrogen flowing, by the solution of sterilizing by 2mL/ branch it is aseptic subpackaged in nose with through going out
In the sterile spray bottle of bacterium processing.
The above content is a further detailed description of the present invention in conjunction with specific preferred embodiments, and it cannot be said that
Specific implementation of the invention is only limited to these instructions.For those of ordinary skill in the art to which the present invention belongs, exist
Under the premise of not departing from present inventive concept, a number of simple deductions or replacements can also be made, all shall be regarded as belonging to of the invention
Protection scope.
Claims (13)
1. a kind of Rupatadine fumarate nasal spray, it is characterised in that: contain in every 1000 mL Rupatadine fumarate nasal spray
There are Rupatadine fumarate 0.1-0.2 g in terms of Rupatadine, chitosan 1-10 g, sodium chloride 4.5-9 g, ethylparaben
0.2-0.5 g, remaining is water for injection.
2. a kind of Rupatadine fumarate nasal spray according to claim 1, it is characterised in that: every 1000 mL richness horse
Contain Rupatadine fumarate 0.15 g in terms of Rupatadine, chitosan 5-8 g, sodium chloride 6-9 in sour Rupatadine nasal spray
G, 0.3 g of ethylparaben, remaining is water for injection.
3. a kind of Rupatadine fumarate nasal spray according to claim 1, it is characterised in that: the nasal spray is 2
ML/ branch.
4. a kind of preparation method of Rupatadine fumarate nasal spray, which comprises the following steps:
(1) it measures about 300 mL of fumaric acid solution and chitosan is added, be sufficiently swollen, dissolve by heating, be denoted as I liquid；
(2) another taking ethylparaben adds 50 mL of distilled water to dissolve by heating, i.e. II liquid；
(3) about 600 mL waters for injection separately are taken, adds Rupatadine fumarate, sodium chloride stirring and dissolving, obtains III liquid；
I liquid, II liquid, III liquid are mixed and stirred evenly, IV liquid is obtained；
(4) IV liquid is filtered, adds to the full amount of water for injection, stirs evenly from filter, sterilized, packing is to get Rupatadine fumarate spray
Nose agent.
5. a kind of preparation method of Rupatadine fumarate nasal spray according to claim 4, it is characterised in that: described
Fumaric acid solution in step (1) refers to concentration for the fumaric acid aqueous solution of 0.5%(w/v)；Its preparation method are as follows: precision claims
0.5 g of fumaric acid is taken, is placed in 100 mL volumetric flasks, being dissolved in water for injection and being diluted to scale to get concentration is 0.5%
Fumaric acid aqueous solution.
6. a kind of preparation method of Rupatadine fumarate nasal spray according to claim 4, it is characterised in that: described
Heating for dissolving temperature in step (1) is 60-70 DEG C of heating water bath dissolution.
7. a kind of preparation method of Rupatadine fumarate nasal spray according to claim 4, it is characterised in that: described
I liquid in step (1) refers to form the chitosan gum liquid solution of clear viscous.
8. a kind of preparation method of Rupatadine fumarate nasal spray according to claim 4, it is characterised in that: described
Heating for dissolving in step (2) refers to that dissolution is boiled in heating.
9. a kind of preparation method of Rupatadine fumarate nasal spray according to claim 4, it is characterised in that: described
I liquid, II liquid, III liquid are mixed and being stirred evenly as I liquid and II liquid to be added in III liquid in step (3), is uniformly mixed.
10. a kind of preparation method of Rupatadine fumarate nasal spray according to claim 4, it is characterised in that: described
Filtration in step (4) is using 0.22 μm of miillpore filter.
11. a kind of preparation method of Rupatadine fumarate nasal spray according to claim 4, it is characterised in that: described
Sterilizing in step (4) is gone out 30min in 100 DEG C of flowing steams.
12. a kind of preparation method of Rupatadine fumarate nasal spray according to claim 4, it is characterised in that: described
Packing in step (5) refers under nitrogen flowing, and the solution of sterilizing is aseptic subpackaged in the sterilized processing of nose by 2 mL/ branch
Sterile spray bottle in.
13. a kind of preparation method of Rupatadine fumarate nasal spray according to claim 4, it is characterised in that: described
Rupatadine fumarate nasal spray pH in step (5) is 4.5-5.5.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101669926A (en) * | 2008-09-11 | 2010-03-17 | 东莞太力生物工程有限公司 | Liquid preparation for dosing nasal cavities and method for making the same |
| CN103108635A (en) * | 2010-06-30 | 2013-05-15 | J·乌里亚奇·Y股份有限公司 | Liquid formulations of rupatadine fumarate |
| CN109692153A (en) * | 2017-10-24 | 2019-04-30 | 北京睿创康泰医药研究院有限公司 | A kind of aqueous solution preparation of Rupatadine fumarate |
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2019
- 2019-05-14 CN CN201910400004.1A patent/CN110123756A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101669926A (en) * | 2008-09-11 | 2010-03-17 | 东莞太力生物工程有限公司 | Liquid preparation for dosing nasal cavities and method for making the same |
| CN103108635A (en) * | 2010-06-30 | 2013-05-15 | J·乌里亚奇·Y股份有限公司 | Liquid formulations of rupatadine fumarate |
| CN109692153A (en) * | 2017-10-24 | 2019-04-30 | 北京睿创康泰医药研究院有限公司 | A kind of aqueous solution preparation of Rupatadine fumarate |
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