CN108853014A - A kind of eye drops and preparation method thereof containing Rupatadine fumarate - Google Patents
A kind of eye drops and preparation method thereof containing Rupatadine fumarate Download PDFInfo
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- 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
- A61K9/08—Solutions
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
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- 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
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- 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
- A61K47/38—Cellulose; Derivatives thereof
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- 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
- A61K9/0048—Eye, e.g. artificial tears
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- 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
Abstract
The invention discloses a kind of eye drops containing Rupatadine fumarate, the eye drops includes following component：The weight ratio of Rupatadine fumarate, Tribulus terrestris, pharmaceutically acceptable eye drops auxiliary material and water for injection, 0.1-0.5g containing Rupatadine fumarate in every 100mL eye drops, the Rupatadine fumarate and Tribulus terrestris is：Rupatadine fumarate：Tribulus terrestris=1:1-3.The present invention, which changes, provides the preparation method of the eye drops.The advantages that eye drops of the invention, therapeutic effect is good, property is stable, toxic side effect is small.
Description
Technical field
The present invention relates to field of medicaments, more specifically to a kind of eye drops and its system containing Rupatadine fumarate
Preparation Method.
Background technique
Allergic conjunctivitis is the common multiple factor of one kind of blinding, is such as not treated in time, can cause the view of irreversibility
Power is lost.Domestic and international many ophthalmologists carried out numerous studies to this pathological process, including clinical diagnosis and treatment and experimentally ground
Study carefully, at present still without a comparatively ideal therapeutic scheme.
Some researches show that histamine is the most inflammatory mediators contained when occurring allergy early stage and symptom, and PAF is then
It is another important inflammatory mediator in airway inflammation, inhibiting the inflammatory mediators activity such as histamine is the emphasis for treating inflammation.Rupatadine
It is to be listed at present uniquely not only with antihistamine effect but also antagonism platelet activating factor (PAF) active antiallergic, can controls
Treat seasonal and catarrhus perennialis.Have scholar using guinea pig ileum functional experiment compare Rupatadine and other the
One, the anti-histamine activity of two generation antihistamines, it was demonstrated that Rupatadine compared with RMI 9918, Loratadine, cetirizine, atarax and
Diphenhydramine has stronger anti-histamine activity.Rupatadine has better lung tissue H1 receptor compared with cerebellum H1 receptor
Selective binding ability, Loratadine but have no similar effect.Base of the Rupatadine to histamine H1-receptor and bradykinin receptor B2
It is inhibited because expressing；Furthermore multinomial external and animal model experiment confirms the effect of Rupatadine antagonism PAF.This
Outside, Rupatadine can also LAD2 type mast cell PAF induction histamine, interleukins (IL) 8, interleukin 4 (IL-
4), the release of IL-5, IL-13 and tumor necrosis factor (TNF), can play to conjunctivitis must therapeutic effect.
Currently, the research of Rupatadine is concentrated mainly on nasal drop and oral agents, such as the middle promulgated by the State Council of CN103108635A
Bright patent document, disclose a kind of Rupatadine fumarate without cyclodextrin aqueous liquid preparation, can be used for treating anaphylaxis
Rhinitis and nettle rash.The preparation includes Rupatadine fumarate, one or more cosolvent and one or more pH adjusting agents,
Wherein the pH of the composition is used to treat anaphylactia between 4 and 6.5.
And the ophthalmic administration research of Rupatadine fumarate at present is less, for ophthalmic administration, under conjunctiva and in vitreum
Injecting drug use can reach effective drug concentration in ocular tissue, but intraocular injection administration is a kind of traumatic to prescription
Method, drug administration by injection, which is repeated several times, can greatly increase the incidence of infectious endophthalmitis.It studies fumaric acid Lu's pa existing part
He is centainly prepared into ophthalmic administration liquid preparation, such as：
The Chinese invention patent file of CN101926762A, discloses a kind of rupatadine fumarate eye drops, the eye drip
Liquid is to be aided with thickener, buffer salt, isotonic agent, bacteriostatic agent, solubilizer using Rupatadine fumarate as main ingredient.Preparation method A is
First a certain amount of water of thickener is dissolved, then by main ingredient, buffer salt, isotonic agent, bacteriostatic agent, a certain amount of water for injection of solubilizer
Dissolution, mixes two kinds of solution, adds appropriate water for injection to required concentration；Preparation method B is by thickener, fumaric acid Lu Pata
Long agitation to solution is clarified together for fixed, buffer salt, bacteriostatic agent, isotonic agent, solubilizer and water for injection, then adds injection
Water to full dose to obtain the final product.The preparation method of rupatadine fumarate eye drops of the present invention is simple, for treating ocular anaphylactia,
Have the characteristics that it is significant in efficacy, nonirritant, have no toxic side effect, stability it is good.
The Chinese invention patent file of CN101669901A discloses a kind of liquid preparation for ophthalmic administration.It is described
Liquid preparation contains the Rupatadine of 0.1-25g/100mL and the cyclodextrin compounds of 0.5-30g/100mL；The present invention
Further relate to the preparation method of the liquid preparation.Liquid preparation of the invention have absorb it is rapid, easy to use, curative for effect,
Stable feature has good curative effect for treatment conjunctivitis, especially allergic conjunctivitis.
Aforesaid liquid preparation, without by injection, reducing the eye loss to drug user, use is safe, but is being directed to
There is also certain limitations in terms of the curative effect of the symptoms such as allergic conjunctivitis, keratitis.
Summary of the invention
Exist for existing Rupatadine fumarate ophthalmic preparations in symptoms curative effects such as treatment allergic conjunctivitis, keratitis
A degree of limitation situation, the purpose of the present invention is to provide one kind with therapeutic effect is good, property is stable, toxic side effect is small
The eye drops containing Rupatadine fumarate, while the present invention also provides the preparation methods of the eye drops.
A kind of eye drops containing Rupatadine fumarate, the eye drops include following component：It is Rupatadine fumarate, white
Tribulus fruit extract, pharmaceutically acceptable eye drops auxiliary material and water for injection contain Rupatadine fumarate in every 100mL eye drops
The weight ratio of 0.1-0.5g, the Rupatadine fumarate and Tribulus terrestris is：Rupatadine fumarate：Tribulus terrestris extracts
Object=1:1-3.
The present invention also provides the preparation methods of the eye drops, include the following steps：Take appropriate water for injection dissolution fumaric acid
Rupatadine and Tribulus terrestris, obtain solution A；Then appropriate water for injection dissolution eye drops auxiliary material is taken, solution B is obtained；
Then solution A is mixed with solution B again, be added remaining injection water to get.
Preparation method when the present invention also provides in the eye drops containing thickener comprising following steps：Take appropriate note
It penetrates and dissolves Rupatadine fumarate and Tribulus terrestris with water, obtain solution A；Then appropriate water for injection dissolution eye drops is taken
Auxiliary material obtains solution B；Appropriate water for injection is taken, thickener is added, refrigeration obtains solution C；Then again by solution B and solution C
Mixed, add solution C mixing, then be added remaining injection water to get.
Eye drops of the invention is able to ascend by the compounding of Rupatadine fumarate and Tribulus terrestris to allergy
The curative effect of the inflammation such as membranous conjunctivitis, keratitis, and the eye drops also has many advantages, such as that property is stable, toxic side effect is small.This hair
Bright preparation method is simple, easy to operate, is convenient for industrialized production.
Specific embodiment
A kind of eye drops containing Rupatadine fumarate, the eye drops include following component：It is Rupatadine fumarate, white
Tribulus fruit extract, pharmaceutically acceptable eye drops auxiliary material and water for injection contain Rupatadine fumarate in every 100mL eye drops
The weight ratio of 0.1-0.5g, the Rupatadine fumarate and Tribulus terrestris is：Rupatadine fumarate：Tribulus terrestris extracts
Object=1:1-3.
Can be the various excipient substances that can be applied to eye drops for pharmaceutically acceptable auxiliary material, as bacteriostatic agent,
A kind of auxiliary material or two or more auxiliary material combinations may be selected in thickener, pH adjusting agent, osmotic pressure regulator in practice.
Wherein, the weight ratio of the bacteriostatic agent and Rupatadine fumarate is：Rupatadine fumarate：Bacteriostatic agent=1:
0.002-5.Bacteriostatic agent can be the various bacteriostatic agents and combinations thereof that can apply on eye drops, as thimerosal, quaternary ammonium salt,
Any or two or more combination during Domiphen, Xian Bitai, anesin, parabens, three pears are sour.
Wherein, the weight ratio of the thickener and Rupatadine fumarate is：Rupatadine fumarate:Thickener=1:
0.1-10.Thickener can be the various thickeners and combinations thereof that can be applied on eye drops；If the thickener is hydroxypropyl
Any one of methylcellulose, methylcellulose, sodium hyaluronate, polyvinyl alcohol, polyvinylpyrrolidone or the kind
Any combination.
In order to adapt to ocular environment, the pH value of the eye drops is 5.5-7；The pH value can be by can be applied to eye drops
Various pH adjusting agents and combinations thereof be adjusted, such as select sodium hydroxide, hydrochloric acid, sodium citrate, the minor official acid of Chinese holly, boric acid, boron
The combination of one or more of sand.
In order to adapt to ocular environment, reducing stimulation and promote absorbing and releasing for drug, the osmotic pressure of the eye drops is dense
Degree is 250-350mOsmol/kg；The osmolality can be by can be applied to the various osmolality regulators of eye drops
And combinations thereof be adjusted, such as select sodium chloride and/or mannitol.
The present invention also provides the preparation methods of the eye drops, can use the existing various preparation works for preparing eye drops
Skill；The present invention also provides the preparation methods of the eye drops, include the following steps：Take appropriate water for injection dissolution fumaric acid Lu Pata
Fixed and Tribulus terrestris, obtains solution A；Then appropriate water for injection dissolution eye drops auxiliary material is taken, solution B is obtained；Then again
Solution A is mixed with solution B, be added remaining injection water to get.
Preparation method when the present invention also provides in the eye drops containing thickener comprising following steps：Take appropriate note
It penetrates and dissolves Rupatadine fumarate and Tribulus terrestris with water, obtain solution A；Then appropriate water for injection dissolution eye drops is taken
Auxiliary material obtains solution B；Appropriate water for injection is taken, thickener is added, refrigeration obtains solution C；Then again by solution B and solution C
Mixed, add solution C mixing, then be added remaining injection water to get.
It is appropriate in preparation method of the present invention, be refer to be added water for injection in substance formed solution can (i.e.
Substance be added can be dissolved), to amount, there is no particular restriction.
Eye drops containing Rupatadine fumarate of the invention, can treat allergic conjunctivitis, keratitis.
In the following, being described further in conjunction with specific embodiment to the present invention：
Embodiment 1-3
Table 1：Embodiment 1-3 eye drops formula table
By technical solution of the present invention, prepares the available auxiliary material kind of eye drops containing Rupatadine fumarate and be not limited to
Kind listed by table can also have following multiple choices：
Such as bacteriostatic agent, so-called any bacteriostatic agent in pharmacy can be used, dosage is by routine dose in pharmacy.
Such as, 1. 0.002%-0.005% thimerosal；2. quaternary ammonium salt (including benzalkonium chloride, benzalkonium bromide), Domiphen, Xian Bitai etc.,
Effective concentration is 0.002%-0.01%；3. alcohols commonly uses 0.3-0.6% anesin；4. parabens commonly use 0.03-
0.06% ethyl hydroxy benzoate；5. acids, such as 0.01-0.08% tri- pears acid.Above each material concentration is volume-weight percent,
I.e. every hundred milliliters contain grams.
Thickener：It can be using common thickener in pharmacy, such as hydroxypropyl methylcellulose, methylcellulose, Hyaluronic Acid
Any combination of any or described kind of sodium, polyvinyl alcohol, polycarbophil, polyvinylpyrrolidone etc., can be used not
The same degree of polymerization finally makes eye drops reach suitable viscosity.
It the use of the pH value that pH adjusting agent adjusts finished product eye drops is 5.5-7.5；The pH adjusting agent is sodium hydroxide, salt
Any combination of any one of the minor official acid of acid, sodium citrate, Chinese holly, boric acid, borax or the kind.
Preparation method is to dissolve Rupatadine fumarate full dose with appropriate water for injection, add Tribulus terrestris and stir
Dissolution is mixed, separately lets cool its dispersion thickener water for injection, is separately adjusted with water for injection dissolution pH adjusting agent, osmotic pressure
Agent, bacteriostatic agent stir evenly filtering, merge two liquid, add the Rupatadine fumarate dissolved, Tribulus terrestris mixing
Liquid adds to the full amount of water for injection, filtering, packing to get.
The stability test of 1 rupatadine fumarate eye drops of experimental example
Accelerated test：Using 0.3% rupatadine fumarate eye drops by the preparation of 2 method of the embodiment of the present invention commercially available
Under terms of packing, it is put into climatic chamber, is placed under conditions of 40 DEG C ± 2 DEG C of temperature, relative humidity 25% ± 5%, respectively
It sampled in the 1st, 2,3,6 month, is measured according to 2015 editions related requests of Chinese Pharmacopoeia on time.It the results are shown in Table 1：
Table 1：Stability test tables of data
Long term test：Using 0.3% rupatadine fumarate eye drops by the preparation of 2 method of the embodiment of the present invention commercially available
Under terms of packing, it is put into climatic chamber, is placed under conditions of 25 DEG C ± 2 DEG C of temperature, relative humidity 40% ± 5%, respectively
It sampled, shines on time in the 3rd, 6,9,12 month《Chinese Pharmacopoeia》2015 editions related requests are measured.Measurement result was measured with 0 month
As a result compare, the results are shown in Table 2：
Table 2：Long term test tables of data
The result shows that：Character is unchanged, it is seen that foreign matter meets regulation；In Related substances separation, related content of material is without bright
The aobvious trend increased, does not occur other impurities, and assay, pH value inspection result have no significant change, sterile to be investigated,
Asepsis growth illustrates that rupatadine fumarate eye drops stability provided by the invention is good.Other of the invention example products also into
It has gone identical test, and has obtained the test result of same trend, being limited by length will not enumerate.
The eye irritation of the rupatadine fumarate eye drops of the invention of experimental example 2 is tested
Lagophthalmos irritation is carried out using by 0.1% rupatadine fumarate eye drops of 1 method of embodiment of the present invention preparation
Test.
6 healthy new zealand rabbits, half male and half female are selected in test.Using androgynous left and right branch hole self-contrast method, left side is given
Rupatadine fumarate eye drops (administration concentration 0.5mg/ml), each administered volume are 100 μ l, and 50 μ l/ drops, totally 2 drip；It is right
Side is given 0.9% isometric sodium chloride injection and is compareed, and daily administration 5 times, successive administration 28 days.Every 1 administration daily
Before, about 1 hour after the last administration the 8th, 15,22 day, observation in 1,2,4 and 24,48,72 hours is whole after the last administration within the 28th day moved
The score value of the local reaction situation of object eyes and in detail recording exceptional situation and eye reaction, appraisal result are 6/6 animal left side
Cornea of right eye, iris have no apparent irritation, and irritative response score value is 0 point；Some Animals right and left eyes occur respectively
The micro- congested phenomenon of iris vessels, but score value is smaller, is 1 point.It is computed, the rabbit right eye stimulate the reaction of each observing time point
Score range is 0-0.067；The score value of right and left eyes is in 0-3 points of nonirritant range；Daily before every 1 administration, the
8,15,22 days about 1 hour after the last administration carries out animal eyes in 1,2,4 and 24,48,72 hours on the 28th day after the last administration
Fluorescent staining inspection, inspection result are that rabbit eyes are showed no obvious abnormalities variation, before first administration, are administered the 8th, 15,22 day
And after the last administration slit lamp examination is carried out to rabbit eyes and is taken pictures within 72 hours for the 28th day, inspection result is that rabbit eyes are showed no
Obvious anomalous variation.
The above result shows that (being given by the developed continuous 28 days multiple eye drips of rupatadine fumarate eye drops of the present invention
Concentration is stoste 0.5mg/ml), lagophthalmos is had no and causes irritative response.Other example products of the invention have also carried out identical
Test, and obtain identical test result, being limited by length will not enumerate.
The rupatadine fumarate eye drops of the present invention of experimental example 3 exempt from mouse pollen-allergic conjunctivitis early reaction phase
Epidemic disease inhibiting effect.
6-8 week old Balb/c female mice 40 is chosen, is randomly divided into 4 groups, every group 10.Respectively normal group, model
Control group, rupatadine fumarate eye drops group, Olopatadine hydrochloride eye drops group carry out the examination of mouse pollen-allergic conjunctivitis
It tests.
Ragweed pollen allergic conjunctivitis model is established, by PBS liquid and Freund's complete adjuvant containing 50 μ g ragweed pollens
Complete by 1: 1 volume ratio mixing, remaining each group is respectively at mouse tail root and left hind foot pad skin in addition to negative control group
Under be injected into the first sensitization of row, each 150 μ L of position, 7d is endless by the ragweed pollen PBS liquid of equivalent and Freund after injection
Full adjuvant carries out enhancing sensitization by intraperitoneal injection after 1: 1 volume ratio mixing completely, and 14d enhances again in the same way
Sensitization.Therapeutic process 7d 21-27d after last enhances sensitization, rupatadine fumarate eye drops group uses real by the present invention
Apply 0.1% rupatadine fumarate eye drops of 1 method of example preparation；Olopatadine hydrochloride eye drops group uses commercially available hydrochloric acid Austria Lip river
He determines eye drops (Pa Tanluo, Alcon), normal group and model control group rat purified water eye drip, and three times a day, 2 drip every time.
After treatment end, every mouse of each experimental group gives the thick immersion liquid of 300 μ g pollen proteins and carries out eye drip excitation.After excitation in 1h,
10% chloral hydrate anesthesia is put to death mouse using eyeball bloodletting, removes eyeball for making the inspection of pathological section row mast cell
It surveys, the serum of collection detects ragweed pollen specific IgE for ELISA.
Clinical symptoms assess all experimental mices after the treatment of relative medicine, excite through ragweed pollen allergen
Afterwards, in microscopically observation mouse sign and clinical assessment is carried out in 30min.Evaluation index includes:Chemosis, conjunctiva fill
Blood, is shed tears at eyelid swelled, by 0-3 points of scorings, formulates standards of grading:Nothing:0 point；Slightly:1 point；Moderate:2 points；Severe:3 points.
This four classifications respectively score summation be total scoring:Eyes have serious conjunctival congestion, oedema, eyelid swelled, the person of shedding tears
Highest scoring is 12 points, and the scoring of moderate patient's highest is 8 points, and slight person's highest scoring is 4 points.
Histopathology is cut eyeball of mouse together with periphery papebral conjunctiva using eye scissors together, this process not broken
Bad conjunctival fornix, 4% poly aldehyde solution are fixed, and routine paraffin wax embedding makes 4 μm of slices, every mouse takes 5 of different level
Slice carries out Switzerland-Giemsa staining, neutral gum mounting, microscopy.Every slice is random under × 400 times of optical microscopies
5 visuals field are observed, mast cell sum in the visual field is counted with mast cell degranulation number, then calculates every group of mouse
Mast cell degranulation percentage.
Ragweed pollen specific IgE level detection excitation 30min post-processes mouse in serum, and eyeball takes blood, is stored at room temperature
4 DEG C of refrigerator overnights are stored in after 2h.Upper serum is drawn after centrifugation, it is special using ragweed pollen in indirect elisa method detection serum
Specific IgE level.According to this laboratory conventional method, it is coated with ragweed pollen crude protein (2ng/ μ L), 4 DEG C are overnight, and 3%
BAS-PBS is closed, and the HRP- sheep anti-Mouse IgE secondary antibody of mice serum, biotin labeling is sequentially added after board-washing, is eventually adding
Developing solution, substrate and terminate liquid read OD value at microplate reader 450nm.Statistical analysis:Using 17.0 software of SPSS to experiment
Data are analyzed, and each experimental data is indicated with mean ± standard deviation (x ± s).Population mean representated by multiple samples compares
Using one-way analysis of variance, the comparison of multiple sample averages between any two uses least significant difference value method (least-
Significant difference, LSD).It is that difference is statistically significant with P < 0.05.
After symptom scores result each group mouse terminates treatment, eye drip excitation is carried out with the thick immersion liquid of ragweed pollen albumen,
After excitation in 30min, score each experimental mice clinical symptoms.
There is apparent allergic symptom in model group mouse, including conjunctival congestion, oedema, eyelid swelled, sheds tears；Fumaric acid
Rupatadine eye drops group and Olopatadine hydrochloride eye drops group it is observed that the clinical symptoms of slight allergic conjunctivitis,
Compared with model group, difference is statistically significant (P < 0.01)；Olopatadine hydrochloride eye drops group and fumaric acid Lu Pata
It is not statistically significant (P > 0.05, table 3) to determine eye drops group comparing difference.
Ocular signs scoring is compared after the excitation of 3 each group mouse allergy original of table
Note：aP<0.05, vs Normal group,bP<0.05, vs model control group
Histopathology coloration result.The mast cell degranulation percentage of negative control group is (27.4 ± 8.47) %,
Model group is (68.6 ± 9.61) %, Olopatadine hydrochloride eye drops group (37.6 ± 6.30) %, Rupatadine fumarate eye drip
Liquid group is (38.4 ± 7.38) %.Compared with negative control group, mast cells infiltration is obvious in remaining each group mouse conjunctival tissue,
Mast cell degranulation percentage increases, and difference is statistically significant (P < 0.05)；Olopatadine hydrochloride eye drops group and rich horse
Mast cells infiltration degree and degranulation percentage and model group are than more significant in sour Rupatadine eye drops group mouse conjunctival tissue
It reduces, difference is statistically significant (P < 0.01), Olopatadine hydrochloride eye drops group and rupatadine fumarate eye drops
Group is compared, no significant difference (P > 0.05).
Ragweed pollen specific IgE antibody in the measurement result each group mice serum of ragweed pollen specific IgE in serum
Level is respectively:Negative control group 0.64 ± 0.25, model group 2.72 ± 0.34, Olopatadine hydrochloride eye drops group 1.43 ±
0.11, rupatadine fumarate eye drops group 1.35 ± 0.12.Ragweed pollen in each group mouse and negative control group mice serum
The horizontal of specific IgE is compared, and difference is statistically significant (P < 0.01)；Compared with model group, Olopatadine hydrochloride
Ragweed pollen specific IgE level is remarkably decreased in eye drops group, hydrochloric acid rupatadine fumarate eye drops group serum, and difference has
Significant statistical significance (P < 0.01)；Rupatadine fumarate eye drops group ragweed pollen specific IgE level is compared with hydrochloric acid Austria Lip river
He determines eye drops group and is declined, but no significant difference (P > 0.05).
Result of study shows that rupatadine fumarate eye drops prepared by the present invention can obviously inhibit mouse pollen hypersensitivity
The generation of mast cell degranulation ratio and ragweed pollen specific IgE in membranous conjunctivitis symptom, early reaction phase, to fumaric acid
Rupatadine allergic conjunctivitis has certain therapeutic effect.
It will be apparent to those skilled in the art that can make various other according to the above description of the technical scheme and ideas
Corresponding change and deformation, and all these changes and deformation all should belong to the protection scope of the claims in the present invention
Within.
Claims (10)
1. a kind of eye drops containing Rupatadine fumarate, it is characterised in that the eye drops includes following component：Fumaric acid Lu
Pa Tading, Tribulus terrestris, pharmaceutically acceptable eye drops auxiliary material and water for injection, containing rich horse in every 100mL eye drops
The weight ratio of sour Rupatadine 0.1-0.5g, the Rupatadine fumarate and Tribulus terrestris is：Rupatadine fumarate：
Tribulus terrestris=1:1-3.
2. eye drops according to claim 1, it is characterised in that：The pharmaceutically acceptable auxiliary material be selected from bacteriostatic agent,
The combination of one or more of thickener, pH adjusting agent, osmotic pressure regulator.
3. eye drops according to claim 2, it is characterised in that the weight ratio of the bacteriostatic agent and Rupatadine fumarate
For：Rupatadine fumarate：Bacteriostatic agent=1:0.002-5.
4. eye drops according to claim 2, it is characterised in that：The bacteriostatic agent is thimerosal, quaternary ammonium salt, Du's rice
Any or two or more combination during sweet smell, Xian Bitai, anesin, parabens, three pears are sour.
5. eye drops according to claim 2, it is characterised in that：The weight ratio of the thickener and Rupatadine fumarate
For：Rupatadine fumarate:Thickener=1:0.1-10.
6. eye drops according to claim 2, it is characterised in that：The thickener is hydroxypropyl methylcellulose, Methyl cellulose
Any one of element, sodium hyaluronate, polyvinyl alcohol, polyvinylpyrrolidone and polycarbophil or two or more combinations.
7. eye drops according to claim 1, it is characterised in that：The pH value of the eye drops is 5.5-7.
8. eye drops according to claim 1, it is characterised in that：The osmolality of the eye drops is 250-
350mOsmol/kg。
9. the preparation method of any one of -8 eye drops according to claim 1, it is characterised in that include the following steps：It takes appropriate
Water for injection dissolves Rupatadine fumarate and Tribulus terrestris, obtains solution A；Then appropriate water for injection dissolution eye drip is taken
Liquid auxiliary material, obtains solution B；Then solution A is mixed with solution B again, be added remaining injection water to get.
10. the preparation method of any one of -8 eye drops according to claim 1, it is characterised in that：In the eye drops auxiliary material
Including thickener, preparation method includes the following steps：Appropriate water for injection dissolution Rupatadine fumarate and tribulus terrestris is taken to mention
Object is taken, solution A is obtained；Then appropriate water for injection dissolution eye drops auxiliary material is taken, solution B is obtained；Appropriate water for injection is taken, is added
Thickener, refrigeration, obtains solution C；Then solution B is mixed again with solution C, adds solution C mixing, it is then added
Remaining water for injection to get.
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Cited By (2)
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| CN110013498A (en) * | 2019-05-10 | 2019-07-16 | 合肥华威药业有限公司 | A kind of eye drops and preparation method thereof of hydrochloric olopatadine |
| CN115068592A (en) * | 2022-06-27 | 2022-09-20 | 长春生物制品研究所有限责任公司 | Recombinant human interferon alpha 1b eye drops stable at normal temperature after unsealing and preparation method thereof |
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| CN110013498A (en) * | 2019-05-10 | 2019-07-16 | 合肥华威药业有限公司 | A kind of eye drops and preparation method thereof of hydrochloric olopatadine |
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