Summary of the invention:
The technical problem to be solved in the present invention provides the pharmaceutical composition that contains levocetirizine, particularly provide absorb fast, bioavailability is high, favourable pharmaceutical solutions form in the treatment, is suitable for the child and the old man takes.
Active ingredient in pharmaceutical of the present invention is levocetirizine or its pharmaceutically acceptable salt.Described pharmaceutically acceptable salt comprises: hydrochlorate, sulfate, phosphate, maleate, citrate, tartrate, palmitate, acetate, nitrate.
Include polyvinylpyrrolidone (PVP K in the adjuvant of said composition
30) as protecting colloid, nonionic surfactant poloxamer as solubilizing agent, PEG400 as stabilizing agent.
Pharmaceutical composition of the present invention is a solution.
Described solution is oral liquid and drop.
Inventor of the present invention is through intensive studies show that, in the aqueous solution of levocetirizine, add polyvinylpyrrolidone, PEG400 and poloxamer, can prevent the chemical degradation of levocetirizine, reduce the generation of related substance, thereby the toxicity of reduction medicine, make it have good safety.Also can reduce the molecular aggregates phenomenon and take place, make solution keep clarification, improve stability of formulation.
In the 1000ml solution, the content of described levocetirizine or its pharmaceutically acceptable salt is that the content of 0.5~20g, polyvinylpyrrolidone is that the content of 20~100g, poloxamer is that the content of 5~50g, PEG400 is 10~250g.
Contain acetic acid-sodium acetate or citric acid-sodium citrate buffer in the pharmaceutical composition of the present invention.The preferred pH value of drug solution is 4.5~6.5.The citric acid-sodium citrate buffer is a preferred reducing agents.
Pharmaceutical composition of the present invention also can comprise various oral liquids adjuvant and other pharmaceutically acceptable adjuvant commonly used, and as correctives, buffer agent, antiseptic, pH regulator agent, the consumption of adjuvant amount ranges is routinely determined.These adjuvant comprise sorbitol, glycerol, propylene glycol, sodium benzoate, methyl hydroxybenzoate, propylparaben, saccharin sodium, strawberry essence etc.
The preparation method of about compositions of the present invention is: levocetirizine, polyvinylpyrrolidone, PEG400, poloxamer and pharmaceutical adjuvant are dissolved in an amount of distilled water, slight fever and stirring make dissolving, add other adjuvant after cold slightly again, stirring makes dissolving, regulating pH value with buffer is 4.5~6.5, adds distilled water diluting to full dose.Filter sterilization.
Liquid preparation of the present invention has good to eat fruit aroma, comfortable taste, and the patient is easy to accept.
The specific embodiment: embodiment 1 levo-cetirizine hydrochloride oral solution
Prescription:
Levo-cetirizine hydrochloride 0.5g
Sorbitol 250g
PEG400 150ml
Polyvinylpyrrolidone 25g
Poloxamer (model is F68) 10g
Propanoic acid 1ml
Saccharin sodium 0.1g
Strawberry essence 1ml
Citric acid-sodium citrate is an amount of
Distilled water adds to 1000ml
Preparation: take by weighing (or measuring) supplementary material by formula ratio, get an amount of distilled water, slight fever and stirring make dissolving, and (get citric acid 30g, add water 200ml, pH is 5.5 ± 0.2 with the sodium hydroxide adjusting, and is standby with the citric acid-sodium citrate buffer.) to regulate pH value be 4.5~6.5, adds distilled water diluting to full dose, with 0.45 μ m filtering with microporous membrane, fill is jumped a queue, and rolls lid, and sterilization (the ASM water-bath is sterilized, 115.5 ℃, 30min) gets final product.Embodiment 2 levo-cetirizine hydrochloride oral solutions
Prescription:
Levo-cetirizine hydrochloride lg
Propylene glycol 100ml
Sorbitol 250g
PEG400 100ml
Polyvinylpyrrolidone 20g
Poloxamer 5g
Sorbic acid 2g
Saccharin sodium 0.1g
Strawberry essence 1ml
Citric acid-sodium citrate is an amount of
Distilled water adds to 1000ml
Preparation: take by weighing (or measuring) supplementary material by formula ratio, get an amount of distilled water, slight fever and stirring make dissolving, and (get citric acid 30g, add water 200ml, pH is 5.5 ± 0.2 with the sodium hydroxide adjusting, and is standby with the citric acid-sodium citrate buffer.) to regulate pH value be 4.5~6.5, adds distilled water diluting to full dose, with 0.45 μ m filtering with microporous membrane, fill is jumped a queue, and rolls lid, and sterilization (the ASM water-bath is sterilized, 115.5 ℃, 30min) gets final product.Embodiment 3 levo-cetirizine hydrochloride oral solutions
Prescription:
Levo-cetirizine hydrochloride 0.5g
Sorbitol 180g
PEG400 10ml
Polyvinylpyrrolidone 100g
Poloxamer (model is F68) 5g
Sorbic acid 2g
Saccharin sodium 0.2g
Apple essence 1ml
Citric acid-sodium citrate is an amount of
Distilled water adds to 1000ml
Preparation: take by weighing (or measuring) supplementary material by formula ratio, get an amount of distilled water, slight fever and stirring make dissolving, and (get citric acid 30g, add water 200ml, pH is 5.5 ± 0.2 with the sodium hydroxide adjusting, and is standby with the citric acid-sodium citrate buffer.) to regulate pH value be 4.5~6.5, adds distilled water diluting to full dose, with 0.45 μ m filtering with microporous membrane, fill is jumped a queue, and rolls lid, and sterilization (the ASM water-bath is sterilized, 115.5 ℃, 30min) gets final product.Embodiment 4 levo-cetirizine hydrochloride oral solutions
Prescription:
Levo-cetirizine hydrochloride 2g
Propylene glycol 100ml
Sorbitol 250g
PEG400 120ml
Polyvinylpyrrolidone 30g
Poloxamer 10g
Sorbic acid 2g
Saccharin sodium 0.2g
Strawberry essence 1ml
Acetic acid-sodium acetate is an amount of
Distilled water adds to 1000ml
Preparation: take by weighing (or measuring) supplementary material by formula ratio, get an amount of distilled water, slight fever and stirring make dissolving, and (get sodium acetate 30g, add water 200ml, pH is 5.5 ± 0.2 with the glacial acetic acid adjusting, and is standby with acetic acid-sodium-acetate buffer.) to regulate pH value be 4.5~6.5, adds distilled water diluting to full dose, with 0.45 μ m filtering with microporous membrane, fill is jumped a queue, and rolls lid, and sterilization (the ASM water-bath is sterilized, 115.5 ℃, 30min) gets final product.Embodiment 5 levo-cetirizine hydrochloride drops
Prescription:
Levo-cetirizine hydrochloride 10g
Propylene glycol 50ml
Sorbitol 200g
PEG400 180ml
Polyvinylpyrrolidone 40g
Poloxamer 10g
Sorbic acid 2g
Saccharin sodium 0.5g
Strawberry essence 1ml
Acetic acid-sodium acetate is an amount of
Distilled water adds to 1000ml
Preparation: take by weighing (or measuring) supplementary material by formula ratio, get an amount of distilled water, slight fever and stirring make dissolving, and (get sodium acetate 30g, add water 200ml, pH is 5.5 ± 0.2 with the glacial acetic acid adjusting, and is standby with acetic acid-sodium-acetate buffer.) to regulate pH value be 4.5~6.5, adds distilled water diluting to full dose, with 0.45 μ m filtering with microporous membrane, fill is jumped a queue, and rolls lid, and sterilization (the ASM water-bath is sterilized, 115.5 ℃, 30min) gets final product.Embodiment 6 levo-cetirizine hydrochloride drops
Prescription:
Levo-cetirizine hydrochloride 10g
Glycerol 20ml
Sorbitol 150g
PEG400 200ml
Polyvinylpyrrolidone 50g
Poloxamer 20g
Sorbic acid 2g
Saccharin sodium 0.5g
Flavoring banana essence 1ml
Acetic acid-sodium acetate is an amount of
Distilled water adds to 1000ml
Preparation: take by weighing (or measuring) supplementary material by formula ratio, get an amount of distilled water, slight fever and stirring make dissolving, and (get sodium acetate 30g, add water 200ml, pH is 5.5 ± 0.2 with the glacial acetic acid adjusting, and is standby with acetic acid-sodium-acetate buffer.) to regulate pH value be 4.5~6.5, adds distilled water diluting to full dose, with 0.45 μ m filtering with microporous membrane, fill is jumped a queue, and rolls lid, and sterilization (the ASM water-bath is sterilized, 115.5 ℃, 30min) gets final product.Embodiment 7 levo-cetirizine hydrochloride drops
Prescription:
Levo-cetirizine hydrochloride 20g
Glycerol 10ml
Sorbitol 150g
PEG400 250ml
Polyvinylpyrrolidone 60g
Poloxamer 50g
Sorbic acid 2g
Saccharin sodium 0.5g
Apple essence 1ml
Citric acid-sodium citrate is an amount of
Distilled water adds to 1000ml
Preparation: take by weighing (or measuring) supplementary material by formula ratio, get an amount of distilled water, slight fever and stirring make dissolving, and (get citric acid 30g, add water 200ml, pH is 5.5 ± 0.2 with the sodium hydroxide adjusting, and is standby with the citric acid-sodium citrate buffer.) to regulate pH value be 4.5~6.5, adds distilled water diluting to full dose, with 0.45 μ m filtering with microporous membrane, fill is jumped a queue, and rolls lid, and sterilization (the ASM water-bath is sterilized, 115.5 ℃, 30min) gets final product.Embodiment 7 stable contrast experiments
The fill of control oral liquid bottle is adopted in all preparations on request of compositions 1~8 in the table 1, the sillicon rubber blocking sealing, and easy-to-draw plastic-aluminum composite cover fore shaft places under the condition of 40 ± 1 ℃ of temperature, RH 75% accelerated test 6 months.Investigate: the clarity of solution, content, related substance.The results are shown in Table 2.
The composition of table 1 compositions (%)
Compositions | ??1 | ??2 | ??3 | ??4 | ??5 | ??6 | ??7 | ??8 |
Levo-cetirizine hydrochloride | ??0.1 | ??1.0 | ??0.1 | ??1.0 | ??0.1 | ??1.0 | ??0.1 | ??1.0 |
Propylene glycol | ??5 | ??5 | ??5 | ??5 | ??5 | ??5 | ??5 | ??5 |
Glycerol | ??5 | ??5 | ??5 | ??5 | ??5 | ??5 | ??5 | ??5 |
Sorbitol | ??25 | ??25 | ??25 | ??25 | ??25 | ??25 | ??25 | ??25 |
PEG400 | ??- | ??- | ??- | ??- | ??- | ??- | ??10 | ??10 |
Polyvinylpyrrolidone | ??- | ??- | ??2.5 | ??2.5 | ??2.5 | ??2.5 | ??2.5 | ??2.5 |
Poloxamer | ??- | ??- | ??- | ??- | ??2.5 | ??2.5 | ??2.5 | ??2.5 |
Sorbic acid | ??0.2 | ??0.2 | ??0.2 | ??0.2 | ??0.2 | ??0.2 | ??0.2 | ??0.2 |
Saccharin sodium | ??0.05 | ??0.05 | ??0.05 | ??0.05 | ??0.05 | ??0.05 | ??0.05 | ??0.05 |
Strawberry essence | ??0.01 | ??0.01 | ??0.01 | ??0.01 | ??0.01 | ??0.01 | ??0.01 | ??0.01 |
Citric acid-sodium citrate | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount |
Distilled water | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount |
Annotate: the citric acid-sodium citrate buffer (get citric acid 30g, add water 200ml, regulate pH with sodium hydroxide and be 5.5 ± 0.2, standby.) regulate pH to 5.5 ± 0.2, add distilled water diluting to full dose 500ml.
Table 2 accelerated test is investigated the result
Compositions | 0 day | 6 months |
Clarity | Content (%) | Related substance (%) | Clarity | Content (%) | Related substance (%) |
??1 | Qualified | ??100.15 | ??0.31 | ??++ | ??98.32 | ??1.91 |
??2 | Qualified | ??99.64 | ??0.34 | ??++ | ??97.96 | ??1.86 |
??3 | Qualified | ??99.89 | ????0.41 | ??+ | ??98.47 | ????1.74 |
??4 | Qualified | ??101.16 | ????0.31 | ??+ | ??99.53 | ????1.71 |
??5 | Qualified | ??99.72 | ????0.32 | Qualified | ??98.43 | ????1.27 |
??6 | Qualified | ??100.37 | ????0.30 | Qualified | ??98.98 | ????1.32 |
??7 | Qualified | ??100.54 | ????0.40 | Qualified | ??99.93 | ????0.65 |
??8 | Qualified | ??99.38 | ????0.38 | Qualified | ??98.87 | ????0.54 |
Annotate 1: "+" representative produces a small amount of insoluble substance; " ++ " representative produces more insoluble substance.
Annotate 2: " related substance " mainly is meant the raw material brought in process of production, intermediate, degradation product, isomer, polymer, side reaction product etc.
The result is as follows: compositions 1 and 2 promptly began to produce insoluble substance after 4 months, and it is nearly 2% that active ingredient content descends, and related substance increases about 1.5%; When compositions 3 and 4 is deposited to 6 months, produce a small amount of insoluble substance, active ingredient contains and descends about 1.6% most, related substance increases about 1.4%: compositions 5 and 6, when depositing, do not see that insoluble substance produces to 6 months, content descends about 1.3%, and related substance increases about 1.0%; Compositions 7 and 8 when depositing to 6 months, does not see that insoluble substance produces, and content descends about 0.6%, and related substance increases about 0.3%.
This experiment shows: the oral liquid of levo-cetirizine hydrochloride is easy to generate insoluble substance; only add the protecting colloid polyvinylpyrrolidone; can not avoid the generation of insoluble substance; and the increase of the decline of active ingredient content, related substance; and after having increased the solubilizing agent poloxamer; though can guarantee the clear and bright of liquid; but the active ingredient fall is still very big; related substances increases nearly 1%; and PEG400 is also joined in the compositions simultaneously, can prepare the oral liquid of metastable levo-cetirizine hydrochloride.Embodiment 8: pharmaceutical composition pharmacodynamics test of the present invention
Levo-cetirizine hydrochloride is third generation H
1The receptor blocking medicine can be special and the H of the mucocutaneous blood vessel of antagonism effectively
1Receptor, clinical allergic rhinitis and the various Mucocutaneous allergic disease that causes by histamine that be used for the treatment of.For verifying the H of pharmaceutical composition of the present invention
1Receptor antagonism and effect characteristics thereof, the spy carries out following test.(1) isolated guinea pig ileum test 1, animal: 12 of healthy qualified one-level Cavia porcelluss, body weight 300-400g, male and female half and half.2, medicine: levo-cetirizine hydrochloride oral administration solution (10ml:5mg is 0.5mg/ml) Cetirizine hydrochloride Tablets (10mg/ sheet): the normal saline solution that is made into 0.5mg/ml with normal saline is standby; Chlorpheniramine maleate tablets (4mg/ sheet): the normal saline solution that is made into 0.5mg/ml with normal saline is standby; Blank oral administration solution: for not containing the oral administration solution that medicine only contains adjuvant; The histamine phosphate normal saline solution: concentration is 0.5mg/ml.3, method: method is put to death Cavia porcellus to tap the head, dissect immediately after the execution, take out ileum, discard near the intestinal segment in the ileocecal valve 10cm, get the intestinal segment of 3cm, put into the little glass dish that fills krebs solution, wherein pass to 95% oxygen and 5% carbon dioxide, bath temperature is 37 ± 0.5 ℃, and specimen preload 2-3g makes 24 specimen altogether.
24 isolated guinea pig ileum specimen are divided into histamine group, histamine at random add that levo-cetirizine hydrochloride oral administration solution group, histamine add the Cetirizine hydrochloride Tablets group, histamine adds the chlorpheniramine maleate tablets group, totally 4 groups, every group of 6 specimen.Add relative medicine respectively in each little glass dish, dosage is respectively histamine group 0.03mg histamine phosphate normal saline solution, histamine adds levo-cetirizine hydrochloride oral administration solution group adding 0.03mg histamine phosphate normal saline solution and 1ml levo-cetirizine hydrochloride oral administration solution, histamine add Cetirizine hydrochloride Tablets group adding 0.03mg histamine phosphate normal saline solution and 2ml levo-cetirizine hydrochloride sheet normal saline solution, histamine add chlorpheniramine maleate tablets group adding histamine phosphate normal saline solution 0.03ml and 2ml chlorpheniramine maleate tablets normal saline solution.Make the antagonism curve of each group respectively, calculate the pA that is subjected to reagent thing and control drug
2Value (amount effect curve that makes agonist is to the parallel negative logarithm that moves the molal quantity of 2 times of required competitive antagonists of high dose direction).4, result: press pA
2Being worth descending arrangement is successively: histamine add the chlorpheniramine maleate tablets group>>histamine adds Cetirizine hydrochloride Tablets group>histamine and adds levo-cetirizine hydrochloride oral administration solution group, histamine adds chlorpheniramine maleate tablets group and histamine and adds the difference that Cetirizine hydrochloride Tablets group, histamine add between levo-cetirizine hydrochloride oral administration solution group and have statistical significance, adds difference not statistically significant between levo-cetirizine hydrochloride oral administration solution group but histamine adds Cetirizine hydrochloride Tablets group and histamine.5, conclusion: levo-cetirizine hydrochloride oral administration solution and Cetirizine hydrochloride Tablets are than first generation H
1The receptor-selective of receptor blocking medicine chlorpheniramine maleate tablets is stronger, and the above two are to the H of intestinal smooth muscle
1The effect of receptor acting is faint, and chlorpheniramine maleate tablets is to the H of intestinal smooth muscle
1Receptor then has tangible blocking effect.The levo-cetirizine hydrochloride oral administration solution is compared the former with Cetirizine hydrochloride Tablets receptor-selective is stronger.(2) rat passive cutaneous anaphylaxis, PCA of the same race (Rat PCA) test (I allergic reaction type model) 1, animal: body weight is 1 of the healthy qualified rat of 90-100g, and body weight is 40 of the healthy qualified rats of 150-200g, male and female half and half.2, medicine: levo-cetirizine hydrochloride oral administration solution (10ml:5mg is 0.5mg/ml) Cetirizine hydrochloride Tablets (10mg/ sheet): the normal saline solution that is made into 0.5mg/ml with normal saline is standby.Pounce on and quick (4mg/ sheet): the normal saline solution that is made into 0.5mg/ml with normal saline is standby.Blank oral administration solution: for not containing the oral administration solution that medicine only contains adjuvant.3, method;
A. sero-fast preparation: getting body weight is the healthy qualified rat of 90-100g, and antigen is the egg protein through sodium sulfate recrystallization 3-5 time, and adjuvant is the daytime to cough the bacillus vaccine, to rat muscle injection 10mg/kg, lumbar injection 2 * 10 simultaneously
10/ bordetella pertussis is put to death the animal blood sampling after 10-14 days, through low-speed centrifugal, and separation of serum, it is standby to put refrigerator.
B. passive sensitization of skin and antigen are attacked: getting body weight is the healthy qualified rat of 150-200g, is divided into 4 groups at random, 10 every group, and totally 40.Under etherization cut off the hair at back, with the dilution antiserum (1: 40 and 1: 60) intradermal injection in the Mus back, each dilution factor is injected 2 points, every some 0.1ml.Irritate stomach to animal after 47 hours and be subjected to the reagent thing, dosage is respectively: levo-cetirizine hydrochloride oral administration solution group 0.6mg/kg; Cetirizine hydrochloride Tablets group 1.1mg/kg; Pounce on and quick group 0.5mg/kg; Blank oral administration solution group 5ml/ only.48 hours posterior veins injection 1ml, 0.5% azovan blue solution (including egg protein 1mg) carry out antigen and attack.Sacrificed by decapitation animal after 20 minutes, the upset skin of back is measured blue diameter of reacting speckle.Its PCA suppresses percentage rate and calculates with following formula: suppress percentage rate=(matched group locus coeruleus diameter-medication group locus coeruleus diameter)/matched group locus coeruleus diameter * 100%.4, result: arrange from big to small and be followed successively by by suppressing percentage rate: levo-cetirizine hydrochloride oral administration solution group>Cetirizine hydrochloride Tablets group>pounce on and quick group>blank oral administration solution group.Wherein the difference of levo-cetirizine hydrochloride oral administration solution group and Cetirizine hydrochloride Tablets group does not have significance (p>0.05), cetirizine hydrochloride oral administration solution, Cetirizine hydrochloride Tablets group and pounce on and quick group with barren difference significance (p≤0.01) is arranged, cetirizine hydrochloride oral administration solution group, Cetirizine hydrochloride Tablets group and pounce on and quick group difference also has significance (p≤0.01).5, conclusion: cetirizine hydrochloride oral administration solution, Cetirizine hydrochloride Tablets and pounce on and quick the I allergic reaction type all had obvious curative effects, quick curative effect is stronger than pouncing on for cetirizine hydrochloride oral administration solution and Cetirizine hydrochloride Tablets, and the cetirizine hydrochloride oral administration solution dosage be Cetirizine hydrochloride Tablets two/once situation under can bring into play equal or higher with it curative effect.(3) skin heart permeability test 1, animal: 50 of healthy qualified rats, body weight 160-240g, male and female half and half.2, medicine: levo-cetirizine hydrochloride oral administration solution (10ml:5mg is 0.5mg/ml) Cetirizine hydrochloride Tablets (10mg/ sheet): the normal saline solution that is made into 0.5mg/ml with normal saline is standby.Blank oral administration solution: for not containing the oral administration solution that medicine only contains adjuvant.The histamine phosphate normal saline solution: concentration is 0.5mg/ml.3, method: 50 rats are divided into the heavy dose of group of levo-cetirizine hydrochloride oral administration solution, middle dosage group, small dose group, Cetirizine hydrochloride Tablets group and blank group (blank oral administration solution), totally 5 groups, 10 every group at random.Feed earlier and observe a week, early morning on the same day was irritated corresponding trial drug of stomach or control drug to it in test, and dosage only is respectively the heavy dose of group of levo-cetirizine hydrochloride oral administration solution 1.1mg/kg, middle dosage group 0.6mg/kg, small dose group 0.3mg/kg, cetirizine hydrochloride group sheet group 2.2mg/kg, blank group 5ml/.The histamine phosphate normal saline solution 0.1ml of 1 hour intradermal injection 0.5mg/ml after the administration, the 1% azovan blue normal saline solution 1ml/kg of intravenous injection simultaneously.Put to death animal after 30 minutes, take off indigo plant and dye skin and shred, soaked 24 hours with 1: 1 acetone normal saline solution, solution centrifugal is got supernatant, with 72-1 type spectrophotometric determination optical density (640nm).Calculate the antagonism that azovan blue content causes by reagent thing and control drug to histamine with reaction vascular permeability increases according to standard curve.4, result: large, medium and small dosage group of levo-cetirizine hydrochloride oral administration solution and Cetirizine hydrochloride Tablets group all effectively the vascular permeability that causes of antagonism histamine increase, with the blank group significant difference (p≤0.01) is arranged relatively; Wherein the antagonism of the heavy dose of group of levo-cetirizine hydrochloride oral administration solution is the strongest (compares there was no significant difference with dosage group in the levo-cetirizine hydrochloride oral administration solution with the Cetirizine hydrochloride Tablets group, compared significant difference p≤0.05 with levo-cetirizine hydrochloride oral administration solution small dose group), there was no significant difference (p 〉=0.05) between dosage group and Cetirizine hydrochloride Tablets group in the levo-cetirizine hydrochloride oral administration solution.5, conclusion: the levo-cetirizine hydrochloride oral administration solution is to the H of skin heart smooth muscle
1Receptor has tangible antagonism, is that the antagonism of Cetirizine hydrochloride Tablets of its twice is identical with dosage.The dosage of dosage group is preferred dose in the levo-cetirizine hydrochloride oral administration solution, recommends to be used for clinical trial (being scaled human dose is: 5mg/ days).(4) shock test 1, animal due to the histamine: 50 of healthy qualified one-level Cavia porcelluss, body weight 200-300g, male and female half and half.2, medicine: levo-cetirizine hydrochloride oral administration solution (10ml:5mg is 0.5mg/ml) Cetirizine hydrochloride Tablets (10mg/ sheet): the normal saline solution that is made into 0.5mg/ml with normal saline is standby.Blank oral administration solution: for not containing the oral administration solution that medicine only contains adjuvant.The histamine phosphate normal saline solution: concentration is 0.5mg/ml.3, method: 50 Cavia porcelluss are divided into the heavy dose of group of levo-cetirizine hydrochloride oral administration solution, middle dosage group, small dose group, Cetirizine hydrochloride Tablets group and blank group (blank oral administration solution), totally 5 groups, 10 every group at random.Feed earlier and observe a week, early morning on the same day was irritated corresponding trial drug of stomach or control drug to it in test, and dosage only is respectively the heavy dose of group of levo-cetirizine hydrochloride oral administration solution 1.34mg/kg, middle dosage group 0.67mg/kg, small dose group 0.33mg/kg, Cetirizine hydrochloride Tablets group 2.68mg/kg, blank group 5ml/.1 hour intravenous injection histamine phosphate normal saline solution 0.2mg/kg causes shock (show as accelerated breathing, dyspnea, drop to even death) after the administration.Observation is subjected to the reagent thing to the incubation period of the shock due to the histamine and the influence of degree.4, result: large, medium and small dosage group of levo-cetirizine hydrochloride oral administration solution and Cetirizine hydrochloride Tablets group and blank group all do not have obvious influence, there was no significant difference between each test group and matched group (p 〉=0.05) to the incubation period and the order of severity of suffering a shock due to the histamine.5, conclusion: levo-cetirizine hydrochloride oral administration solution and Cetirizine hydrochloride Tablets are invalid to the anaphylactic shock due to the histamine.
Above-mentioned result of the test proves that pharmaceutical composition of the present invention has the anti-H of height
1Receptor active, its H
1Receptor blocking usefulness and dosage are that the usefulness of Cetirizine hydrochloride Tablets of its twice is suitable even higher, and the dosage of recommending to be used for clinical trial is 5mg/ days; Compare the levo-cetirizine hydrochloride oral administration solution with Cetirizine hydrochloride Tablets and have higher receptor-selective, so the safety of medicine is higher.Therefore the levo-cetirizine hydrochloride oral administration solution is a kind of novel anti allergic drug of highly effective and safe.
Preparation according to the present invention is elaborated by embodiment, but it should be considered as limitation of the present invention.