CN1548121A - Soft antiviral capsule and its prepn - Google Patents
Soft antiviral capsule and its prepn Download PDFInfo
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- CN1548121A CN1548121A CNA031250610A CN03125061A CN1548121A CN 1548121 A CN1548121 A CN 1548121A CN A031250610 A CNA031250610 A CN A031250610A CN 03125061 A CN03125061 A CN 03125061A CN 1548121 A CN1548121 A CN 1548121A
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Abstract
The present invention is soft antiviral capsule and it preparation. The soft capsule consists of soft capsule casing and inside medicine. The inside medicine includes water soluble part and volatile oil part in the ratio of 90 g to 1 ml, the water soluble part includes effective component in 30-35 wt% and medicinal supplementary material in 65-70 wt%, and the volatile oil part includes volatile oil in 65-70 wt% and medicinal supplementary material in 30-35 wt%. The volatile oil is prepared with curcuma root, grassleaved sweetflag rhizome, cablin potchouli herb and forsythia; and the water soluble effective component is prepared with curcuma root, grassleaved sweetflag rhizome, cablin potchouli herb and forsythia after extracting volatile oil as well as isatis root, gypsum, reed rhizome, etc. The soft antiviral capsule has more volatile oil, raised bioavailability, and higher curative effect than available antiviral oral liquid in treating common cold.
Description
Invention field
The dosage form that the present invention relates to antivirus oral liquid is improved, and specifically, is a kind of soft capsule dosage form; The present invention also provides the preparation method of this antiviral soft capsule in addition.
Background technology
Soft capsule is meant that a certain amount of medicinal liquid is sealed in spherical or the oval-shaped soft capsule material, and soft capsule material is made by gelatin, glycerol or other suitable medicinal materials.The elasticity of soft capsule material is relevant with the weight ratio between dry gelatin and plasticizer and the water, and suitable usually weight ratio is that dried plasticizer and dry gelatin are 0.4-0.6: 1.0, and water is 1: 1 with the ratio of dry gelatin.Plasticizer commonly used is glycerol, sorbitol or its mixture.
Can fill various oils in the soft capsule material or gelatin is not had liquid medicine, drug solution or the solid dispersion suspension in liquid of dissolution, also can fill solid drugs or solid dispersion.If general medicine is hydrophilic, can in medicine, keep 5% water, make the solvent of medicine or the medium of suspension with oil, and then be filled in the soft capsule material.
" ministry standard " recorded antivirus oral liquid, but it only to disclose be to be that raw material is processed into oral liquid by Radix Isatidis, Gypsum Fibrosum, Rhizoma Phragmitis, the Radix Rehmanniae, Radix Curcumae, Rhizoma Acori Graminei, the Rhizoma Anemarrhenae, Herba Pogostemonis and Fructus Forsythiae.Chen Qiong etc. are at " Chinese patent medicine " 1997, the preparation of open antivirus oral liquid in 19 (9) the 49th pages, be to be raw material with Radix Isatidis 900g, Gypsum Fibrosum 400g, Rhizoma Phragmitis 425g, Radix Rehmanniae 225g, Radix Curcumae 175g, Rhizoma Acori Graminei 175g, Rhizoma Anemarrhenae 175g, Herba Pogostemonis 200g and Fructus Forsythiae 325g, decoct with water twice, add for the first time 8 times in water, decocted 2 hours, and collected volatile oil; For the second time add 6 times in water, decocted 1.5 hours, merge decoction liquor and add ethanol precipitation, reclaim ethanol, concentrate, filter with volatile oil and be mixed and made into oral liquid 1000ml.This oral liquid has the effect of clearing heat and expelling damp and removing pathogenic heat from blood and toxic substance from the body, cures mainly anemopyretic cold, epidemic febrile disease heating, is applicable to viral infection illness such as upper respiratory tract infection, influenza, parotitis.But clinical use and store in find antivirus oral liquid because Radix Curcumae, Rhizoma Acori Graminei, Fructus Forsythiae, Herba Pogostemonis medical material in the raw material all contain volatile oil, and these volatile oil are effective ingredient, and the water insoluble decocting liquid of volatile oil in the oral liquid, so content is less, thereby directly influence the curative effect of oral liquid; There is the problem of poor stability in this oral liquid in addition; Taking to carry also makes troubles for the patient.And soft capsule dosage form has the characteristic that comprises oily matter well, and makes oily matter stable, take also more convenient than oral liquid, so soft capsule is more suitable dosage form.For this reason, we have developed the antiviral soft capsule dosage form.
Summary of the invention
The purpose of this invention is to provide a kind of antiviral soft capsule.
Another object of the present invention has provided the preparation method of this antiviral soft capsule.
Antiviral soft capsule of the present invention, form by soft capsule material and content, wherein content partly is made up of water-soluble portion and volatile oil, containing 30-35% aqueous soluble active constituent and 65-70% pharmaceutic adjuvant in the water-soluble portion forms, contain 65-70% volatile oil and 30-35% pharmaceutic adjuvant in the volatile oil part, wherein said volatile oil is to be made by 5.8% Radix Curcumae, 5.8% Rhizoma Acori Graminei, 6.7% Herba Pogostemonis and 10.8% Fructus Forsythiae; The dry powder that wherein said aqueous soluble active constituent is by 5.8% Radix Curcumae, 5.8% Rhizoma Acori Graminei, 6.7% Herba Pogostemonis and 10.8% Fructus Forsythiae, 30% Radix Isatidis, 13.3% Gypsum Fibrosum, 14.2% Rhizoma Phragmitis, 7.5% Radix Rehmanniae, 5.8% Rhizoma Anemarrhenae water extract-alcohol precipitation of preparation behind the volatile oil, concentrate, spray drying is made.
The pharmaceutic adjuvant of water-soluble portion is one or more of diluent and/or cosolvent, antioxidant, and the pharmaceutic adjuvant of volatile oil part is cosolvent and water.
Diluent in the pharmaceutic adjuvant of water-soluble portion is for being selected from Polyethylene Glycol, propylene glycol, vegetable oil, the mineral oil preferred PEG400.
Diluent in the adjuvant of water-soluble portion is PEG400 and water.The PEG400 of water-soluble portion and the weight ratio of water are 19: 4.
Also contain 5-10% glycerol in the pharmaceutic adjuvant of the water-soluble portion of the content of antiviral soft capsule of the present invention.
Water-soluble portion the best of antiviral soft capsule content of the present invention is aqueous soluble active constituent 33.3%, PEG400 52.8%, water 11.1% and glycerol 2.8%.
The pharmaceutic adjuvant of volatile oil part is diluent and cosolvent
Diluent in the pharmaceutic adjuvant of volatile oil part is a water, and cosolvent is a tween 80.
The content of tween 80 wherein is 0.01-0.03% (g/ml).
The volatile oil of the content of preferred antiviral soft capsule of the present invention partly is volatile oil effective ingredient 66%, water 33.98% and tween 80 0.02%.
As best-of-breed technology scheme of the present invention, the volatile oil of the content of antiviral soft capsule of the present invention partly is volatile oil effective ingredient 66%, water 33.98% and tween 80 0.02%; The water-soluble portion of content is aqueous soluble active constituent 33.3%, PEG400 52.8%, water 11.1% and glycerol 2.8%, and the ratio of the two is 90g: 1ml.
The raw material composition and the consumption of contained effective ingredient preparation are as follows in the antiviral soft capsule:
Radix Curcumae 5.8%, Rhizoma Acori Graminei 5.8%, Herba Pogostemonis 6.7%, Fructus Forsythiae 10.8%, Radix Isatidis 30%, Gypsum Fibrosum 13.3%, Rhizoma Phragmitis 14.2%, the Radix Rehmanniae 7.5% and the Rhizoma Anemarrhenae 5.8%.
When the medical material in the above-mentioned prescription was prepared into soft capsule dosage form, the problem that needs to solve was the effective ingredient that extracts fully in the medical material, selects suitable adjuvant that these effective ingredient are made capsule 's content then, is pressed into soft capsule at last.
Effective ingredient contained in the antiviral soft capsule of the present invention is made up of the volatile oil of Radix Curcumae, Rhizoma Acori Graminei, Herba Pogostemonis and Fructus Forsythiae and the extract of above-mentioned raw materials.
The volatile oil of Radix Curcumae, Rhizoma Acori Graminei, Herba Pogostemonis and Fructus Forsythiae can adopt the conventional extractive technique of any extraction volatile oil, as steam distillation or carbon dioxide supercritical fluid extraction technology etc.Preferably adopt steam distillation to extract volatile oil Radix Curcumae, Rhizoma Acori Graminei, Herba Pogostemonis and Fructus Forsythiae.The extraction of volatile oil can be that the single medical material extracts mixing then respectively or these a few flavor medical materials extract volatile oil together.Preferably extract volatile oil together.
The extract of above-mentioned raw materials is that above-mentioned medical material and all the other medicines that will extract volatile oil adopt decoction and alcohol sedimentation technique or ethanol extract from water precipitation to be extracted together.The preferred decoction and alcohol sedimentation technique that adopts extracts.Preferably extract is made dry powder.If adopt decoction and alcohol sedimentation technique to extract, the number of times of extraction and contain alcohol amount parameter and must be selected.Among the present invention with dry powder must measure, indigo, indirubin in the catalpol in the representative composition Radix Rehmanniae, Radix Isatidis, the content of forsythin in the Fructus Forsythiae be screening index to decocting number of times, containing alcohol and measure in addition screening study.
The water logging that the residue medical material is added 8 times of amounts was steeped 3 hours, adding medicinal liquid and the medicinal residues of having collected volatile oil again decocted 2 hours, merge decoction liquor, be evaporated to 200% (50 ℃ of mensuration), add 95% ethanol and make and contain alcohol amount and reach 75%, placement is spent the night, filter, with filtrate recycling ethanol, spray drying, promptly.The system portion boils once except that the decocting that the medicinal residues that decocted for the second time add 6 times of amounts more in addition, collecting decoction, and concentrating under reduced pressure, all the other operations are the same, and result of the test sees Table 1 and 2.
The different number of times dry powder yield results (n=3) that decoct of table 1
| Decoct number of times | Dry powder quantities received (g) | Dry powder yield (%) |
| 2 times | 304.7 | ?14.2 |
| 3 times | 336.0 | ?15.7 |
Decocting twice dry powder yield of three ratio decoctions increases by 1.5% approximately, accounts for 9.3% of total dry powder weight.
The representative component content measurement result of table 2 (in rate of transform %)
| Decoct number of times | Indigo (%) | Indirubin (%) | Catalpol (%) | Forsythin (%) |
| 2 times | 51.6 | ?55.8 | 81.9 | ?55.1 |
| 3 times | 54.7 | ?55.0 | 78.1 | ?56.3 |
With representative composition extracted amount is index, decocts 2 times or 3 times, and it is less that extracted amount differs, and catalpol content 2 ratios 3 times on the contrary is high.So it is comparatively suitable to extract twice.
To containing the selection research of alcohol amount.Decoct twice by last method, medicinal liquid is concentrated into 200%, is divided into waiting two parts, a 95% ethanol that adds, and adjusting ethanol content is 80%, another part adjustment concentration of alcohol is 60%.Placement is spent the night, filtering precipitation, the filtrate spray do dry powder.Calculate the dry powder yield, and measure in the content of representative composition and the last method and contain alcohol amount 75% relatively, the results are shown in Table 3 and 4.
Table 3 difference contains alcohol amount dry powder yield result
| Contain alcohol amount (%) | Dry powder yield (%) |
| 60％ | 17.9 |
| 75％ | 14.2 |
| 80％ | 12.2 |
By in the table 3 as seen, increase along with containing alcohol amount, the dry powder yield reduces gradually, 75% then reduce when above not obvious.Considering that soft capsule solids saturation is limited, is 60% o'clock so contain alcohol amount concentration, and the preparation dosage form can be brought difficulty, and it is comparatively suitable to contain alcohol amount 75% o'clock.
Table 4 difference contains the assay result (in rate of transform %) of representative composition in the alcohol amount gained dry powder
| Contain alcohol amount (%) | Indigo (%) | Indirubin (%) | Catalpol (%) | Forsythin (%) |
| 60％ | 54.2 | ?58.1 | ?85.5 | ?59.0 |
| 75％ | 51.6 | ?55.8 | ?81.9 | ?55.1 |
| 80％ | 48.1 | ?53.2 | ?77.7 | ?50.8 |
By in the table 4 as seen, representative component content difference is little, there was no significant difference between each content.
To decoct twice, and contain alcohol amount 75% post precipitation gained precipitate and carry out representative component content mensuration, the results are shown in Table 5.
Representative composition measurement result in the pure precipitate of table 5
| Indigo | Indirubin | Catalpol | Forsythin |
| Do not have | Do not have | Do not have | Do not have |
Representative component content is very low in the alcohol precipitate, almost can not measure.
So selected decoct twice, determining alcohol is 75% for preferred.
Having prepared effective ingredient, is that above-mentioned effective ingredient is made soft capsule content with that.It is to select the suitable dilution agent that above-mentioned effective ingredient is made soft capsule content problem to be solved.And the selection of diluent must be considered the characteristic of effective ingredient.With regard to above-mentioned effective ingredient, wherein existing fat-soluble volatile oil has water miscible extract dry powder again, so volatile oil and extract dry powder can be made suspension or made solid dispersion.Preferably make suspension.When the preparation suspension, diluent can be selected for use in Polyethylene Glycol, propylene glycol, vegetable oil, the mineral oil, preferred PEG400.If select PEG400 as diluent, it can make water soluble ingredient and liposoluble constituent in the medical material all obtain in various degree dissolving, disperse with molecularity, and insoluble composition can be disperseed in liquid feeding homogenize process largely, helped the performance of curative effect composition.
When making drug suspension, can also add suspending agent in the filling drug suspension of the present invention.For oily substrate, normally used is 10%-30% oil wax mixture, and 1 part of preferred oil with hydrogenated soybean, 1 part in Cera Flava and fusing point are 33-38 ℃ 4 parts of short chain vegetable oil.For non-oily substrate, the PEG4000 or 6000 of suspending agent 1%-15% commonly used.If necessary, the present invention can also add stabilizing agent and the bioavailability that antioxidant, surfactant improve soft capsule.
Because the character and the suspension of the medicine of filling influence each other to soft capsule material, for example PEG400 has induration to the gelatin softgel shell, so preferably add the plasticizer of 5-10%, preferred 5% glycerol.
So antiviral soft capsule of the present invention preferably is substrate with PEG400, more preferably also contain plasticizer such as the glycerol of 5-10%.
The processing of solids content will consider that also it is mixed with mobile and dispersion stabilization problem behind the suspension, mobile investigate with room temperature following 45 ℃ tilt can free-flows for meeting the requirements, the test of the different saturations of process, result such as following table 6:
Mobile and the dispersion stabilization result of the test of the content of the different solid saturations of table 6
| Solids saturation (g/g) | 0.50 | 0.33 | 0.15 |
| Mobile | Defective | Defective | Qualified |
| Dispersion stabilization | Coalescent sedimentation is arranged | Coalescent sedimentation is arranged | Coalescent sedimentation is arranged |
| +++ | ++ | + |
By last table 6 result as can be known, solid contents reduces, flowability better, but dispersion stabilization is all relatively poor.The inventor is surprised to find that, when solid contents 0.33 (g/g) adds the water of 5-10% again, its result of the test mobile and dispersion stabilization shows that during water content 10%, flowability is fine, and is homodisperse.So preferably contain water in the pharmaceutic adjuvant of the water-soluble portion of the content of soft capsule of the present invention, the weight ratio of PEG400 and water is 19: 4.
The preferred capsule of soft capsule of the present invention heavily is about 0.45g, and every capsule solids is 0.15g, 4 of each clinical consumptions.
According to volatile oil yield and the each recommended dose of soft capsule, should contain the volatile oil 33ml of Radix Curcumae, Rhizoma Acori Graminei, Herba Pogostemonis and Fructus Forsythiae in per 10000 soft capsules.Because employed substrate is water-soluble base, effective ingredient be mixed, must earlier volatile oil be prepared into Emulsion, again with this Emulsion, pressed powder and substrate mix homogeneously.The preparation of volatile oil part is to add entry in volatile oil, adds Tween 80 again, mix homogeneously, and homogenize is placed observation and is had or not oil to separate out, and the result shows that placing 10 days no oil separates out.
The preparation of soft capsule content of the present invention is made water-soluble portion with glycerol, PEG400, solid dry powder and water mixing exactly, adds volatile oil part mixing again and obtains content.The preparation of preferred soft capsule content of the present invention is with glycerol, PEG400, solid dry powder and water mixing, and homogenize 30 minutes adds volatile oil Emulsion mixing again, and homogenize 30 minutes is made.
Preparation of soft capsule of the present invention is exactly that the foregoing thing is made by the conventional preparation method of soft capsule.The conventional preparation method of these soft capsules comprises dropping preparation method, pressing.Preferred pressing.
Through above-mentioned selection test, draw the preparation method of antiviral soft capsule of the present invention, it comprises the following steps:
Take by weighing Radix Curcumae 5.8%, Rhizoma Acori Graminei 5.8%, Herba Pogostemonis 6.7% and Fructus Forsythiae 10.8%, extract volatile oil, add water and an amount of Tween 80 in volatile oil, mix homogeneously is made the volatile oil part of content;
The medicinal residues of said extracted being crossed volatile oil add Radix Isatidis 30%, Gypsum Fibrosum 13.3%, Rhizoma Phragmitis 14.2%, the Radix Rehmanniae 7.5%, the Rhizoma Anemarrhenae 5.8%, water extract-alcohol precipitation, spray drying obtains solids dry powder, this dry powder and PEG400, G ﹠ W mix homogeneously is made the water-soluble portion of content;
The volatile oil of content is partly added mix homogeneously in the water-soluble portion, make content;
Get the foregoing thing and soft capsule material is pressed into soft capsule.
In order to obtain better effect, the preferred preparation method of antiviral soft capsule of the present invention is:
Take by weighing Radix Curcumae 5.8%, Rhizoma Acori Graminei 5.8%, Herba Pogostemonis 6.7% and Fructus Forsythiae 10.8%, add 8 times of water gagings and soak, being heated to boils extracted volatile oil in 1 hour; In volatile oil, add half water and 2% Tween 80, mix homogeneously, the volatile oil part of content is made in homogenize 10 minutes;
The medicinal residues of said extracted being crossed volatile oil add the Radix Isatidis 30% that had steeped with the water logging of 8 times of amounts, Gypsum Fibrosum 13.3%, Rhizoma Phragmitis 14.2%, the Radix Rehmanniae 7.5%, the Rhizoma Anemarrhenae 5.8%, mix, heating decocted 2 hours, filter, collect filtrate, again medicinal residues are added 6 times of water gaging heating and decocted 2 hours, filter, abandon medicinal residues, merge medicinal liquid, being evaporated to 50 ℃ of survey density is 1.15-1.30, adds ethanol, make that to contain determining alcohol be 75%, decompression recycling ethanol, spray drying obtain solids dry powder, with this dry powder and water, glycerol, the PEG400 mix homogeneously, the water-soluble portion of content is made in homogenize 30 minutes;
Volatile oil with content partly adds the water-soluble portion mix homogeneously again, and content is made in homogenize 30 minutes;
Get the foregoing thing and soft capsule material is pressed into soft capsule.
Antiviral capsules of the present invention whenever contains volatile oil 3.3ml in its 1000 capsules, is higher than volatile oil contents in the oral liquid far away.In addition, antiviral capsules stability of the present invention is very good, can long term store and the deposited phenomenon of antivirus oral liquid can not occur.This capsule also carries easily and takes.
Through finding that with the contrast test of antivirus oral liquid the curative effect of antiviral soft capsule treatment flu is better than antivirus oral liquid.Be in particular in body temperature curative effect aspect, antiviral soft capsule treatment group cure-remarkable-effectiveness rate is 76.70%, and total effective rate is 91.26%; The cure-remarkable-effectiveness rate of antivirus oral liquid is 50.48%, and total effective rate is 72.38%.Aspect the tcm symptom curative effect, antiviral soft capsule treatment group cure-remarkable-effectiveness rate is 84.54%, and total effective rate is 94.55%; The cure-remarkable-effectiveness rate of antivirus oral liquid is 60.75%, and total effective rate is 88.79%.Relatively, learn by statistics and handle between two groups, be P＜0.01, significant differences is arranged.Treatment group curative effect is better than matched group.Antiviral soft capsule treatment group fever patient is 9.633 hours at take medicine back body temperature average onset time, and the average onset time of antivirus oral liquid matched group is 14.343 hours, and relatively, there is significant difference P＜0.05 between group.
Concrete embodiment
Embodiment 1
Take by weighing Radix Curcumae 625g, Rhizoma Acori Graminei 625g, Herba Pogostemonis 715g and Fructus Forsythiae 1160g, add 8 times of water gagings, 50 ℃ flooded 1 hour, and reheat is collected volatile oil to boiling 1 hour, and medicinal liquid and medicinal residues are standby; Radix Isatidis 3220g, Gypsum Fibrosum 1430g, Rhizoma Phragmitis 1520g, Radix Rehmanniae 800g and Rhizoma Anemarrhenae 625g are soaked 8 times of water gagings 3 hours, add in the medicinal residues and medicinal liquid of Radix Curcumae, Rhizoma Acori Graminei, Herba Pogostemonis and the Fructus Forsythiae of carrying volatile oil again, merging post-heating boiled 2 hours, filter, decocted again 2 hours, filter, merging filtrate is evaporated to 200%, 50 ℃ of heat are surveyed density 1.15-1.30, add ethanol and reach 75% to containing the alcohol amount, placement is spent the night, and filters, with the ethanol reclaim under reduced pressure in the filtrate, spray drying obtains solids dry powder.With the volatile oil 33ml that makes, add 1.0g Tween 80 mix homogeneously, add water 17ml, with mulser emulsifying 10 minutes, get volatile oil Emulsion; Other gets the 125g glycerol of recipe quantity, PEG400,1501g solid dry powder and the 516.5g water mixing of 2375g, and homogenize 30 minutes adds volatile oil Emulsion mixing again, and homogenize 30 minutes obtains soft capsule content; Gained content and soft capsule material are pressed into 10000 soft capsules with rolling capsule machine.
Experimental example 1 soft capsule content of the present invention is to the influence test of the physical property of capsule shells
This test is in order to investigate the influence of content to the capsule shells physical property.The soft capsule material of soft capsule generally is made up of dry gelatin, plasticizer and water, and normally used is 1: the dry gelatin of 0.4-0.6 and plasticizer, the soft capsule that 1: 1 water and dry gelatin are formed.But influence each other between the character of the medicine of filling and the soft capsule material.The content of above-mentioned configuration is packed in the gelatine capsule, and room temperature is placed and was investigated capsule shells phenomenon such as whether leak, break, soften, become fragile in 30 days.The results are shown in following table 7.
Table 7 content is to the influence of softgel shell physical property
| Standing time (my god) | 0 | 10 | 20 | 30 |
| The softgel shell character | Flexible, nothing is leaked | Flexible, nothing is leaked | Flexible, nothing is leaked | Flexible, nothing is leaked |
| Do not have softening | Do not have softening | Do not have softening | Do not have softening |
By result in the table 7 as can be known, content does not have influence to gelatin shell.
The disintegration test of experimental example 2 antiviral soft capsule
The disintegration of soft capsule and selected excipient substance relation are very big.If the disintegration of soft capsule is undesirable, also must adjust the selection of excipient.Through the disintegration test, minimum 42 minutes of 5 batch sample disintegrations, the longest 49 minutes, be respectively 45,43,42,47,49 minutes, all meet the regulation of soft capsule.
The clinical comparison test of experimental example 3 antiviral soft capsule and antivirus oral liquid treatment flu
One, test crowd: meet acute upper respiratory tract infection diagnostic criteria, the Chinese medical discrimination person that belongs to the wind-heat syndrome.The course of disease is within 48 hours, and the age is at 18-65 between year.
Two, dosage regimen:
Test group: antiviral soft capsule, 4/time, take every day 3 times after the meal half an hour
Matched group: antivirus oral liquid, 1/time, take every day 3 times after the meal half an hour.
The course of treatment: 3 days
Three, observation index:
A. safety detects: general physical examination, blood, urine, stool routine examination, liver function (ALT), renal function (Cr, BUN) inspection, electrocardiogram;
B. health giving quality observation:
Related symptoms sign: heating, pharyngalgia, distending pain in the head, nasal obstruction, the turbid tears of stream, aversion to wind, cough, picture of the tongue, pharyngeal mucous membrane hyperemia.
C. diagnostic index: the positive bit slice of total white blood cells and classification, Chest X-rays or breast.
Four, EXPERIMENTAL DESIGN: at random, positive drug parallel control, multi-center clinical trial
Five, therapeutic evaluation: work out with reference to " the clinical research guideline of new Chinese medicine treatment flu ".
A. total effects criterion:
Clinical recovery: primary symptom body temperature is normal, the pharyngalgia transference cure, therapeutic index (n) 〉=95%;
Produce effects: primary symptom body temperature is normal, the pharyngalgia symptom disappears substantially, and therapeutic index (n) reduces 〉=75%;
Effectively: primary symptom body temperature, pharyngalgia make moderate progress, and therapeutic index (n) reduces 〉=40%＜75%;
Invalid: treat 3 days with not decline or the rising of interior body temperature, the sings and symptoms of flu does not have substantially
Improve, therapeutic index (n) reduces＜40%.
B. body temperature curative effect determinate standard:
Recovery from illness: treat in 24 hours, temperature recovery is normal, and does not have repeatedly;
Produce effects: treat in 24 hours, body temperature reduces more than 〉=1.0 ℃, but not to normal;
Effectively: treat in 24 hours, body temperature reduces by 0.5 ℃-1.0 ℃ (not containing 1.0 ℃), but not to normal;
Invalid: treat in 24 hours, body temperature reduces by 0.5 ℃ of less than.
C. body temperature onset time criterion
Onset time: begin to 0.5 ℃ of required time of body temperature decline from taking medicine first;
The analgesic time: begin to drop to the normal body temperature required time to body temperature from taking medicine first.
D. tcm symptom criterion of therapeutical effect:
Judge the symptom curative effect according to integration method:
Therapeutic index (n)=(integration before treating-treatment back integration)/integration * 100% before treating
Clinical recovery: therapeutic index (n) 〉=95%;
Produce effects: therapeutic index (n) 〉=75%;
Effectively: therapeutic index (n) 〉=40%＜75%;
Invalid: therapeutic index (n)＜40%.
Six, statistical analysis technique:
A. case is checked and accepted: strict with scheme, the case observation table is filled in, and must not lack a perforated scrofula of neck.
B. to not medication in accordance with regulations, can't judge curative effect, or data is not congruent affects the treatment or safe judgement person, is rejected, reject case and should describe reason in detail.
C. the statistical disposition of clinical data.
The NDST statistical software that main SPSS10.0 of employing and the Sun Ruiyuan of Wannan Medical College edit analyzes.Statistic of test that relevant check provides and corresponding P value thereof are checked with two lavatories, with P≤0.05 for statistical significance is arranged.This test measurement index represents that with mean and standard deviation generally paired t-test is relatively used in front and back in the group, relatively uses t check in groups before and after test group and the matched group between the changing value; Two classification indicators relatively use four fold table, two groups of grading indexs relatively use Wilcoxon method and check.
Seven, result of the test:
Antiviral soft capsule treatment group cure-remarkable-effectiveness rate 83.64%, total effective rate 95.45%; Antivirus oral liquid matched group cure-remarkable-effectiveness rate is 59.81%, total effective rate 88.79%.Body temperature curative effect aspect, antiviral soft capsule treatment group cure-remarkable-effectiveness rate is 76.70%, total effective rate is 91.26%; The cure-remarkable-effectiveness rate of antivirus oral liquid is 50.48%, and total effective rate is 72.38%.Aspect the tcm symptom curative effect, antiviral soft capsule treatment group cure-remarkable-effectiveness rate is 84.54%, and total effective rate is 94.55%; The cure-remarkable-effectiveness rate of antivirus oral liquid is 60.75%, and total effective rate is 88.79%.Relatively, learn by statistics and handle between two groups, be P＜0.01, significant differences is arranged.Treatment group curative effect is better than matched group.
Antiviral soft capsule treatment group fever patient is 9.633 hours at take medicine back body temperature average onset time, and the average onset time of antivirus oral liquid matched group is 14.343 hours, and relatively, there is significant difference P＜0.05 between group.
Eight, safety results:
By to blood, urine, just routine and liver, renal function, electrocardiogram lab testing, do not find obvious toxic-side effects in the clinical trial.Do not see that treatment is preceding normal, unusual person appears in the treatment back.Do not see obvious adverse reaction.
Nine, conclusion
Antiviral soft capsule has no adverse reaction being better than antivirus oral liquid aspect the curative effect of treatment flu, and toxic and side effects is not found in safety.
Claims (14)
1. antiviral soft capsule, it is made up of soft capsule material and content, it is characterized in that content partly is made up of water-soluble portion and volatile oil, containing 30-35% aqueous soluble active constituent and 65-70% pharmaceutic adjuvant in the water-soluble portion forms, contain 65-70% volatile oil and 30-35% pharmaceutic adjuvant in the volatile oil part, wherein said volatile oil is to be made by 5.8% Radix Curcumae, 5.8% Rhizoma Acori Graminei, 6.7% Herba Pogostemonis and 10.8% Fructus Forsythiae; The dry powder that wherein said aqueous soluble active constituent is by 5.8% Radix Curcumae, 5.8% Rhizoma Acori Graminei, 6.7% Herba Pogostemonis and 10.8% Fructus Forsythiae, 30% Radix Isatidis, 13.3% Gypsum Fibrosum, 14.2% Rhizoma Phragmitis, 7.5% Radix Rehmanniae, 5.8% Rhizoma Anemarrhenae water extract-alcohol precipitation of preparation behind the volatile oil, concentrate, spray drying is made.
2. according to the described antiviral soft capsule of claim 1, wherein the pharmaceutic adjuvant of water-soluble portion is one or more of diluent and/or cosolvent, antioxidant, and the pharmaceutic adjuvant of volatile oil part is cosolvent and water.
3. according to the described antiviral capsules of claim 2, wherein the diluent in the pharmaceutic adjuvant of water-soluble portion is for being selected from Polyethylene Glycol, propylene glycol, vegetable oil, the mineral oil.
4. according to the described antiviral capsules of claim 3, wherein the diluent in the adjuvant of water-soluble portion is PEG400 and water.
5. according to the described antiviral capsules of claim 4, wherein the weight ratio of the PEG400 of water-soluble portion and water is 19: 4.
6. according to the described antiviral capsules of claim 5, wherein also contain 5-10% glycerol in the pharmaceutic adjuvant of water-soluble portion.
7. according to the described antiviral capsules of claim 6, wherein the water-soluble portion of content is aqueous soluble active constituent 33.3%, PEG400 52.8%, water 11.1% and glycerol 2.8%.
8. according to the described antiviral capsules of claim 1, wherein the pharmaceutic adjuvant of volatile oil part is diluent and cosolvent
9. according to the described antiviral capsules of claim 8, wherein the diluent in the pharmaceutic adjuvant of volatile oil part is a water, and cosolvent is a tween 80.
10. according to the described antiviral capsules of claim 9, the content of tween 80 wherein is 0.01-0.03% (g/ml).
11. according to the described antiviral capsules of claim 10, wherein the volatile oil of content partly is volatile oil effective ingredient 66%, water 33.98% and tween 80 0.02%.
12. according to any one described antiviral soft capsule among the claim 1-11, wherein the volatile oil of content partly is volatile oil effective ingredient 66%, water 33.98% and tween 80 0.02%; The water-soluble portion of content is aqueous soluble active constituent 33.3%, PEG40052.8%, water 11.1% and glycerol 2.8%, and the ratio of the two is 90g: 1ml.
13. the preparation method of the antiviral soft capsule described in the claim 12, it comprises the following steps:
Take by weighing Radix Curcumae 5.8%, Rhizoma Acori Graminei 5.8%, Herba Pogostemonis 6.7% and Fructus Forsythiae 10.8%, extract volatile oil, add water and an amount of Tween 80 in volatile oil, mix homogeneously is made the volatile oil part of content;
The medicinal residues of said extracted being crossed volatile oil add Radix Isatidis 30%, Gypsum Fibrosum 13.3%, Rhizoma Phragmitis 14.2%, the Radix Rehmanniae 7.5%, the Rhizoma Anemarrhenae 5.8%, water extract-alcohol precipitation, spray drying obtains solids dry powder, this dry powder and PEG400, G ﹠ W mix homogeneously is made the water-soluble portion of content;
The volatile oil of content is partly added mix homogeneously in the water-soluble portion, make content;
Get the foregoing thing and soft capsule material is pressed into soft capsule.
14. according to the described antiviral soft capsule preparation method of claim 13, wherein:
Take by weighing Radix Curcumae 5.8%, Rhizoma Acori Graminei 5.8%, Herba Pogostemonis 6.7% and Fructus Forsythiae 10.8%, add 8 times of water gagings and soak, being heated to boils extracted volatile oil in 1 hour; In volatile oil, add half water and 0.02% Tween 80, mix homogeneously, the volatile oil part of content is made in homogenize 10 minutes;
The medicinal residues of said extracted being crossed volatile oil add the Radix Isatidis 30% that had steeped with the water logging of 8 times of amounts, Gypsum Fibrosum 13.3%, Rhizoma Phragmitis 14.2%, the Radix Rehmanniae 7.5%, the Rhizoma Anemarrhenae 5.8%, mix, heating decocted 2 hours, filter, collect filtrate, again medicinal residues are added 6 times of water gaging heating and decocted 2 hours, filter, abandon medicinal residues, merge medicinal liquid, being evaporated to 50 ℃ of survey density is 1.15-1.30, adds ethanol, make that to contain determining alcohol be 75%, decompression recycling ethanol, spray drying obtain solids dry powder, with this dry powder and water, glycerol, the PEG400 mix homogeneously, the water-soluble portion of content is made in homogenize 30 minutes;
Volatile oil with content partly adds the water-soluble portion mix homogeneously again, and content is made in homogenize 30 minutes;
Get the foregoing thing and soft capsule material is pressed into soft capsule.
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| CN1368122A (en) * | 2001-02-02 | 2002-09-11 | 杨孟君 | Nano antivirus medicine and its preparing process |
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