CN1404825A - Novel decanoy acetaldelzy sodium intravenous preparation and its preparing method thereof - Google Patents

Abstract

The houttuynine sodium intravenous injection composition comprises (by 1000 ml) 20 mg-2000 mg of houttuynine sodium, 7-30g of Tween-80 and the rest is injection water or isotonic solution. Its preparation method includes the following steps: using 32mg-2000 mg of houttuynine sodium (its purity is above 98%, and is determined by using high-performance liquid chromatography) and 7-30g of Tween-80, dissolving them in injection water or isotonic solution, regulating pH value to 5.0-6.2, filtering the said solution and adding injection water or isotonic solution to 1000 ml, fine filtering, filling, sealing and sterilizing so as to obtain the invented product.

Description

Novel decanoy acetaldelzy sodium intravenous and preparation method thereof

Technical field

The present invention relates to novel decanoy acetaldelzy sodium intravenous and preparation method thereof.

Background technology

With the synthetic neo-houttuyninum of chemical method (Neo-Houttuyninum), chemical name is a lauroyl acetaldehyde sodium sulfite, with the effective ingredient houttuynine sodium bisulfite (Houttuyninum) in the natural houttuynine sodium bisulfite, chemistry decanoylacetaldehyde by name is isonomic sodium sulfite addition product, and both pharmacological actions are similar substantially with curative effect.The preparation made from neo-houttuyninum at present has new houttuynine sodium bisulfite injection, now records in the 1177th～1178 page of " Guangdong Province's drug standard " (1987 editions volume two), and this kind is an antibiosis anti-inflammatory drug.Be used for all kinds of inflammation of gynecological such as adnexitis, pelvic inflammatory disease, chronic cervicitis.And be used for upper respiratory tract infection, chronic bronchitis, pneumonia etc., intramuscular injection during use.Because pain appears in this medicine when intramuscular injection, the patient produces the feared state of mind in use; Raw material is owing to purity not high (production technology and detection method defective cause) simultaneously, and this medicine was easily separated out in storage period; And the curative effect of intramuscular injection has influenced the use and the curative effect of this medicine not as good as intravenous drip.

Summary of the invention

The invention provides novel decanoy acetaldelzy sodium intravenous and preparation method thereof.

Of the present invention novel decanoy acetaldelzy sodium intravenous, contain neo-houttuyninum 20mg～2000mg in per 1000 milliliters of injection, tween 80 7～30g, surplus is water for injection or isosmotic solution.

Novel decanoy acetaldelzy sodium intravenous preparation method: (purity is more than 98% to get neo-houttuyninum 32mg～2000mg, with high effective liquid chromatography for measuring), tween 80 7～30g, with water for injection or isosmotic solution dissolving, regulate pH5.0～6.2, above-mentioned solution adds water for injection or isosmotic solution to 1000 milliliter after filtering, passes through embedding behind the fine straining again, sterilization.

But above-mentioned isosmotic solution sodium chloride, potassium chloride, magnesium chloride, calcium chloride, sodium lactate, glucose, xylitol, sorbitol or dextran isosmotic solution.

Above-mentioned novel decanoy acetaldelzy sodium intravenous technology is simple, and what make novel decanoy acetaldelzy sodium intravenously can be used for intravenous drip, is to use conveniently safety, product evident in efficacy.

The specific embodiment Embodiment 1

Get the about 600ml of water for injection (or glucose isosmotic solution), boil, add the mixed liquor that contains 2000mg neo-houttuyninum and 10g tween 80, stirring and dissolving adds injection water (or isosmotic solution) to 900ml, transfers pH5.0～6.2, stirring and dissolving, filter, on container, add water for injection (or isosmotic solution) to total amount, fine straining, the check intermediate products, (can be injection with small volume or high-capacity injection, specification 2ml/ props up in embedding, 5ml/ props up, the 50ml/ bottle, the 100ml/ bottle, the 250ml/ bottle, the 500ml/ bottle), 100 degrees centigrade, sterilization in 30 minutes, clarity test, packing, promptly. Embodiment 2

Get the about 600ml of water for injection (or glucose isosmotic solution), boil, add the mixed liquor that contains 32mg neo-houttuyninum and 20g tween 80, stirring and dissolving adds injection water (or isosmotic solution) to 900ml, transfers pH5.0～6.2, stirring and dissolving, filter, on container, add water for injection (or isosmotic solution) to total amount, fine straining, the check intermediate products, (can be injection with small volume or high-capacity injection, specification 2ml/ props up in embedding, 5ml/ props up, the 50ml/ bottle, the 100ml/ bottle, the 250ml/ bottle, the 500ml/ bottle), 100 degrees centigrade, sterilization in 30 minutes, clarity test, packing, promptly.Above-mentioned preparation novel decanoy acetaldelzy sodium intravenous carries out following safety test:

1. toxicity test: getting body weight is 17～20g healthy mice, 5 every group, totally 10 groups, in mouse tail vein injection this product (1mg/ml) 0.5ml, in 48 hours, does not see any poisoning symptom and the phenomena of mortality.

2. subacute toxicity test: get 40 of Cavia porcelluss, be divided into 2 groups, 20 supply drug test, and 20 compare test, packet numbering, press 8 milligrams of consumption per day per kilograms, divide 2 times lumbar injection, successive administration is after 30 days, put to death, take out tissues such as the heart, liver, kidney, lung, do the pathology cut sections for microscopic examination respectively, do not see that experimental group has specific lesions.3. intravenous injection blood vessel irritation test

Get 12 of new zealand rabbits, male and female half and half, body weight 2.0～2.5kg divides 2 groups, and 6 every group, rabbit ear edge intravenous injection new houttuynine sodium bisulfite injection (1mg/ml) 3ml/kg, injection speed is per minute 2.0ml.Another group is given the equivalent normal saline, once a day, successive administration 5 days, put to death animal in the last administration after 24 hours, cut off ear and be positioned over fixed preparation in 10% formalin, carry out histological examination in 5 sections of rabbit ear edge venous different parts (begin entad to hold do a section from the injection site) section then every 0.5cm.

Rabbit ear edge vein tissue sections observation is the result show: medication group rabbit ear edge venous tissue changes similar to matched group, each rabbit ear edge venous blood tube wall is complete, do not see pathological changes such as endothelial injury, surrounding tissue edema, the vein blood vessel structure is normal, does not see that blood vessel has serious irritant reaction such as tangible degeneration, necrosis.4. hypersensitive test

18 of extracting waste Cavia porcelluss, body weight 280～350g, male and female half and half.Be divided into three groups, every group 6, new houttuynine sodium bisulfite injection (1mg/ml), normal saline and ovum are organized from protein liquid (100mg/kg), the corresponding solution 0.5ml of lumbar injection totally 3 times, is equally divided into two groups again with above-mentioned each treated animal next day of respectively, one group of after first administration the 14th day, only distinguish auricular vein injection new houttuynine sodium bisulfite injection and normal saline 2ml/, ovalbumin liquid (1000mg/kg) is attacked, and observes.Surpass 2 grades as the classification of anaphylaxis progression, judge that promptly anaphylaxis is positive.

Cavia porcellus anaphylaxis progression standards of grading are as follows:

Order of reaction reaction symptom

0 grade of no significant reaction

1 grade is had only and slightly grabs nose, trembles or perpendicular hair

2 grades have several times and cough, grab nose, tremble or perpendicular hair

3 grades repeatedly or continuously cough, with dyspnea or spasm, tic etc.

4 grades of spasm, tic, gatism, shock death

The result shows that Cavia porcellus injecting back 14 days and 21 days first, new houttuynine sodium bisulfite injection group and normal saline matched group, anaphylaxis progression is below 2, and the average anaphylaxis progression of positive control ovalbumin group is 4, shows that new houttuynine sodium bisulfite injection can not cause the Cavia porcellus anaphylaxis.5. hemolytic test

Get one of new zealand rabbit,, to the small beaker of clean dried, remove Fibrinogen with the bamboo let stirring from heart extracting blood 10ml, add normal saline 10ml, the centrifugal supernatant of abandoning adds the 10ml normal saline again, shakes up gently, centrifugal, abandon supernatant, till not taking on a red color to supernatant several times so repeatedly; Measuring blood cell 2ml adds normal saline and is diluted to 2% suspension and uses for test.

Get 14 in test tube, numbering is arranged on the test tube rack, according to the form below adds respectively organizes solution, 11st, 12 pipes do not add for test agent solution, still do not add test solution as blank the 13rd, 14 pipes, and replace normal saline with distilled water, as hemolytic positive control, each pipe is shaken up gently, and insulation is 3 hours in 37 degrees centigrade of water-baths, takes out the back by following criterion record result.The result is as shown in table 1.

The result judges phenomenon

The complete clear and bright redness of haemolysis solution, the pipe end, is acellular residual

Clear and bright redness of part haemolysis solution or brown, the pipe end, have a small amount of erythrocyte residual

No lyse red blood cell all sinks, the supernatant liquid achromatism and clarity

Though assemble not haemolysis, erythrocyte aggregation appears, can not disperse after the jolting

Table 1 new houttuynine sodium bisulfite injection hemolytic test is investigated the result

Test tube number	??1	????2	??3	??4	??5	??6	??7	??8	??9	??10	??11	??12	??13	??14
															New houttuynine sodium bisulfite injection (ml)	??0.1	????0.1	??0.2	??0.2	??0.3	??0.3	??0.4	??0.4	??0.5	??0.5
Normal saline (ml)	??2.4	????2.4	??2.3	??2.3	??2.2	??2.2	??2.1	??2.1	??2.0	??2.0	??2.5	??2.5
															Distilled water (ml)													??2.5	??2.5
2% red blood cell suspension (ml)	??2.5	????2.5	??2.5	??2.5	??2.5	??2.5	??2.5	??2.5	??2.5	??2.5	??2.5	??2.5	??2.5	??2.5
															3.0 hours results of 37 ℃ of insulations	??-	????-	??-	??-	??-	??-	??-	??-	??-	??-	??-	??-	??+	??+

Annotate: +++complete hemolysis; ++ part haemolysis; + coagulation; Coagulation does not take place in-haemolysis not yet

Novel decanoy acetaldelzy sodium intravenous concentration is 1mg/ml

From table the result as seen, new houttuynine sodium bisulfite injection did not cause haemolysis in 3 hours, be the physiology isotonic solution, prompting can not cause haemolysis behind the intravenously administrable.

Claims (3)

1, a kind of novel decanoy acetaldelzy sodium intravenous, it is characterized in that: contain neo-houttuyninum 20mg～2000mg in per 1000 milliliters of injection, tween 80 7～30g, surplus is water for injection or isosmotic solution.

2, described novel decanoy acetaldelzy sodium intravenous by claim 1, it is characterized in that: but described isosmotic solution sodium chloride, potassium chloride, magnesium chloride, calcium chloride, sodium lactate, glucose, xylitol, sorbitol or dextran isosmotic solution

3, the described novel decanoy acetaldelzy sodium intravenous preparation method of claim 1, carry out according to the following steps: get neo-houttuyninum 32mg～2000mg, tween 80 7～30g, with water for injection or isosmotic solution dissolving, and adjusting pH5.0～6.2, add water for injection or isosmotic solution to 1000 milliliter after filtering, pass through embedding behind the fine straining again, sterilization.