CN1294925C - Chinese medicine for treating hypertension and hyperlipemia and preparation thereof - Google Patents
Chinese medicine for treating hypertension and hyperlipemia and preparation thereof Download PDFInfo
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- CN1294925C CN1294925C CNB2004100222179A CN200410022217A CN1294925C CN 1294925 C CN1294925 C CN 1294925C CN B2004100222179 A CNB2004100222179 A CN B2004100222179A CN 200410022217 A CN200410022217 A CN 200410022217A CN 1294925 C CN1294925 C CN 1294925C
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- chinese medicine
- hyperlipidemia
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Abstract
The present invention discloses traditional Chinese medicine for curing high blood pressure and hyperlipidemia and a preparation method thereof. The traditional Chinese medicine is prepared from raw materials, such as fresh pine needles, kudzuvine root, etc., and has the advantages of rapid effective component dissolution, high biological availability, prccise hyperlipidemia prevention curative effect, prccise hyperlipidemia cure curative effect, etc.
Description
Invention field
The present invention relates to a kind of Chinese medicine for the treatment of hypertension and hyperlipidemia and preparation method thereof, particularly a kind of is the pharmaceutical preparation that raw material is made through specific formulation technology by specific extracting method with the Chinese crude drug, and commodity are called SONGLING XUEMAIKANG.
Background technology
According to health ministry recent statistics numeral: Chinese hyperpietic has reached 1.34 hundred million, prevalence 11.88%, and increase progressively with annual 3500000 surprising numeral.By the heart of caused by hypertension, the mortality rate of cerebrovascular complication, occupy China disease death rate first place.
Hyperlipemia is meant that the concentration of one or more compositions in the blood plasma lipide surpasses a kind of disease of normal high limit [cholesterol (TC) and triglyceride (TG) individual event or two unusual risings].From clinical cardinal symptom, can be summarized in the category of diseases such as the traditional Chinese medical science " dizzy ", " thoracic obstruction ", " apoplexy ", think that liver (gallbladder), kidney and spleen (stomach) are its major lesions position; Deficiency of kidney-essence, insufficiency of the spleen mistake fortune is its main endogenous cause of ill; The turbid cohesion of expectorant, injecting blood vessels is its crucial pathogenesis; Phlegm and blood stasis, deposition blood mansion, it is that its development develops into must lapsing to of cardio-cerebrovascular disorder that sering is lost gentle.
Because improving constantly of living standard, hyperlipidemia incidence has and increases gradually and to the trend of middle-aged population development, hyperlipemia is the significant risk factor of cardiovascular and cerebrovascular disease, be the primary risk factor of atherosclerosis (AS), the cardiovascular and cerebrovascular disease due to the AS is one of current principal disease that jeopardizes human health and life.In addition, hyperlipemia also can cause presbyacusis, fatty liver, increase the weight of carrying out property nephrotic syndrome etc., and therefore, hyperlipemia has become one of focus of metabolic disease research in recent ten years.Wherein, U.S. cardiopulmonary blood academy carries out the coronary heart disease study on prevention confirmation in 7 years, and the application of lipid lowerers can reduce by 24% deaths from heart disease rate, reduce by 19% non-lethality heart attack rate, simultaneously, hypolipidemic can also delay or alleviate the development of AS pathological changes, and promotes it to disappear.
The patent No. be 95108297.3 " the hypertensive Chinese patent medicines of a kind of treatment " patent disclosure the hypertensive Chinese patent medicine of a kind of treatment, and the production technology for preparing this Chinese patent medicine, its pharmaceutical dosage form are provided is hard capsule.The present invention is improvement and the raising on the basis of patent 95108297.3, and it is having significant difference with former patent aspect prescription, manufacturing process and clinical practice, the clinical effectiveness.
There is following shortcoming in the patent 95108297.3:
First: generally speaking, when used medical material was dry and soft leaf or bright Folium Pini in not particularly pointing out certain medicine, we thought at conventional meaning and are meant dry and soft leaf (referring to the 1254th page of " Chinese medicine voluminous dictionary " first volume).So we think that it is meant dry and soft leaf the Folium Pini in the patent 95108297.3.Folium Pini needs bright Folium Pini could be filled a prescription after super-dry after plucking, because bright Folium Pini drying is untimely will be putrid and deteriorated, cause very difficulty and complicated of medical material pre-treatment, need to consume a large amount of energy, the production cost height, also increased the chance that medical material pollutes, effective ingredient also can destroyed or volatilization in the dry run.
Second: adopting dry and soft leaf is the medicine of crude drug preparation, and it has shown certain effect on the prevention hyperlipidemia, and effect is not obvious aspect the treatment hyperlipidemia.
The 3rd: select the hard capsule dosage form for use, extract powder need be granulated and crossed 40 mesh sieves among the preparation technology, causes the medicine dissolution rate slow and bioavailability is poor.
The 4th: choice of drug hard capsule dosage form, because the dry extract hygroscopicity is strong, need under the environment of relative humidity 60%, produce during capsule charge in the production, production supplemental equipment requirement height, energy resource consumption is big, the production cost height.
The 5th: select the hard capsule dosage form for use, since poorly sealed, the easy moisture absorption, the necessary good airproof performance of commercially available back, packing cost height.
The 6th: select the hard capsule dosage form for use, because poorly sealed, and filling can not wash the capsule outer surface after intact, causes outer surface to attach medicated powder, has the bad smell and the bitterness of medicine when causing taking, and patient's drug compliance is poor.
The 7th: select the hard capsule dosage form for use and must select capsule for use No. 0, the capsule volume is big, and viscosity is strong, patient's dysphagia.
Summary of the invention
At prior art, the objective of the invention is to overcome above deficiency, provide a kind of and replace dry and soft leaf, can treat the Chinese medicine preparation that hypertension can prevent and treat hyperlipidemia again with bright Folium Pini.
The present invention is implemented by following scheme.
The crude drug prescription of medicine of the present invention is as follows:
Bright Folium Pini 2500g～5000g Radix Puerariae 400～800g
Margarita layer powder 50～120g
The preferred feedstock medicine composition of medicine of the present invention is:
Bright Folium Pini 3000～4000g Radix Puerariae 500～700g
Margarita layer powder 80～100g
Pharmaceutical preparation optimum feed stock medicine composition of the present invention is:
Bright Folium Pini 3600g Radix Puerariae 600g Margarita layer powder 90g
The preparation method of medicine of the present invention mainly is: bright Folium Pini, the Radix Puerariae medical material of getting above-mentioned consumption proportion, decoct with water twice, for the first time add 6～9 times of water gagings, decocted 1～2 hour, add the water of 5～8 times of amounts for the second time, decocted 1～2 hour, collecting decoction filters, and filtrate decompression is condensed into that relative density detects 70 ℃ the time is 1.1～1.3 extractum, getting extractum liquid carries out spray drying and gets dry extract: behind dry extract and Margarita layer powder and adjuvant mix homogeneously, make preparation.
The preparation of medicine of the present invention can be a said dosage form on any pharmaceutics, and wherein preferred dosage form is a soft capsule.
The soft capsule preparation method concrete steps of medicine of the present invention are as follows:
Step 1: extract: bright Folium Pini, the Radix Puerariae medical material of getting formula ratio, decoct with water twice, add for the first time 6～9 times of water gagings, decocted 1～2 hour, and added the water of 5～8 times of amounts for the second time, decocted 1～2 hour, collecting decoction, filter, and filtrate decompression is condensed into that relative density detects 70 ℃ the time is 1.1～1.3 extractum, gets extractum liquid and carry out spray drying and get dry extract;
Step 2: the preparation gelatin solution: the ratio of gelatin, glycerol, water is 10: 4～6: 8～12;
Step 3; The preparation of medicinal liquid: get the suspending agent thermosol in substrate, slowly drop into step 1 gained dry extract and Margarita layer powder, fully handle with colloid mill behind the mix homogeneously;
Step 4: pill: with medicinal liquid and gelatin solution, be pressed into the soft capsule of predetermined weight, through the drying of finalizing the design, wash ball, packing promptly by pellet press.
Wherein:
Decoct with water twice in the step 1, add 8 times of water gagings for the first time, decocted 1.5 hours, add the water of 6 times of amounts for the second time, decocted 1.5 hours; To be condensed into that relative density detects in the time of 70 ℃ be 1.2 extractum to filtrate decompression in the step 1; The spray drying condition is in the step 1: advance 220 ℃ of tower pathogenic wind-warm, go out 100-110 ℃ of tower pathogenic wind-warm.
The gelatin solution ratio is in the step 2: 5: 2: 5.
Suspending agent in the step 3 is Cera Flava, monostearate, paraffin oil, aluminum monostearate or ethyl cellulose; Suspending agent in the step 3 is Cera Flava or aluminum monostearate; Suspending agent in the step 3 is Cera Flava 2～20g; Suspending agent in the step 3 is Cera Flava 5～15g; Substrate in the step 3 is soybean oil, Oleum Arachidis hypogaeae semen, vegetable oil or PEG400; Substrate in the step 3 is soybean oil or Oleum Arachidis hypogaeae semen; Substrate in the step 3 is soybean oil 200～800g; Substrate in the step 3 is soybean oil 300～600g.
The invention has the advantages that:
1, bright Folium Pini replaces dry and soft leaf, prevents that bright Folium Pini from the loss of effective ingredient taking place in dry run, and economical.
2, the invention medicine has not only kept the effect of treatment hypertension and prevention hyperlipidemia, also can treat hyperlipidemia, and curative effect is better than the medicine in the patent 95108297.3.
3, preferred soft capsule in the preparation of invention medicine is so preparation technology's Chinese medicine powder need not to granulate.Medicated powder can be become superfine suspendible liquid substance with substrate by milling treatment of colloid, this suspension system is become soft capsule.
4, soft capsule can overcome the shortcoming of hard capsule, and it is fast to have the effective ingredient of a making stripping, the bioavailability height, sealing fully, loading amount accurately, be convenient to swallow, easy to carry, bad smell and the bitterness that can effectively cover medicine.
The specific embodiment
The advantage that replaces dry and soft leaf prescription below by evidence the present invention with bright Folium Pini.
1, the present invention is by a large amount of study of pharmacy experiments, bright Folium Pini and dry and soft leaf have been carried out systematic study on Main Ingredients and Appearance, the result proves that the effective ingredient of bright Folium Pini and dry and soft leaf mainly all contains volatile oil, flavones ingredient, calabash Bu Su and several amino acids etc., and both content on main component is basically identical; But from thin layer chromatography and high-efficient liquid phase chromatogram as can be seen, bright Folium Pini contains the composition that some do not have in dry and soft leaf collection of illustrative plates, may be volatile oil and some aminoacid ingredients, perhaps this can explain with bright Folium Pini and treat better reason on the hyperlipidemia with dry and soft leaf as crude drug as the crude drug ratio.
2, to adopt consumption be its toxicity of medicine of the crude drug preparation formed of the bright Folium Pini of dry and soft leaf twice and treat hypertensive therapeutic equivalence by the long-term blood pressure lowering therapeutic test proof of a large amount of acute toxicity testings, experimental hypertension rat acute drop test, experimental hypertension rat.
3, high fat rabbit is transferred the blood fat test
3.1 experiment material
3.1.1 medicine
(code name: XSL): obtain dry extract and Margarita layer powder mix homogeneously promptly by optimum feed stock medicine composition among the present invention and process for preparing medicine, lot number is 990902 to medicated powder of the present invention.
(code name: LSL): obtain dry extract and Margarita layer powder mix homogeneously promptly by the optimum weight proportioning of 95108297.3 patent disclosures and production technology, lot number is 990901 to patent 95108297.3 medicated powder.
Positive control drug lovastatin capsule: specification: the 20mg/ grain, lot number: 990111, authentication code: (98) are defended the accurate word X-22-2 of medicine number.Provide by Zhaodong, China Dark Longjiang China rich Pharmaceutical Co., Ltd.
High fat reagent:
1. cholesterol: import packing, specification: 100g/ bottle, lot number: 950704.Provide by chemical reagent wholesale department, Guangzhou.
2. methylthiouracil: 100mg/ sheet, 100 slices/bottle, lot number: 950105.Pharmaceutical factory provides by state-run Wujin, changzhou.
3. Adeps Sus domestica: buy from market.
3.2 laboratory animal
Japan large ear rabbit, body weight 1.8～2.2kg, 50, male and female half and half.The quality certification number: real moving Guan Zhidi 99-11 number of river.Plant provides by the Sichuan laboratory animal.
The high lipid food prescription:
Normal feedstuff: 95% cholesterol: 0.2%
Adeps Sus domestica: 5% methylthiouracil: 0.005%
3.3 instrument: the big general II type biochemical instruments of Holland
3.4 dosage setting
| Dosage (medicated powder g/kg) | Be equivalent to human dosage multiple (doubly) | |
| XSL LSL | 0.2 0.6 1.2 0.2 0.6 1.2 | 3 9 18 3 9 18 |
3.5 experimental technique
Get 75 of healthy qualified white big ear rabbits, body weight 1.8～2.2kg, male and female half and half, at constant temperature laboratory (20 ℃), animal via divides cage to feed general pain feedstuff observation adaptation after 8 days, and serum is isolated in each rabbit ear vein blood sampling, measures T-CHOL (TC) respectively; Triglyceride (TG); Low-density lipoprotein cholesterol (LDL-C); C-VLDL (VLDL-C); The normal value of HDL-C (HDL-C).Feed (February continuously) the normal diet except that 8 rabbit continuation every day of blank group, all the other animals are changed and feed high lipid food (February).After raising January, each rabbit ear portion takes a blood sample once more and detects above-mentioned every index.High fat animal is divided equally 8 groups according to the blood lipid level stratified random, 8 every group.Except that model group, the positive controls rabbit is irritated stomach lovastatin capsule 8mg/kg every day; Irritate stomach XSL and LSL medicated powder all the other 6 groups of every days, dosage is respectively and contains medicated powder 0.2g, 0.6g and 1.2g/kg body weight (irritating the long-pending 3ml/kg that is of body of stomach).During the administration, observe animal food-intake and active situation every day, weigh weekly once, adjust dosage.Behind the successive administration one month, each rabbit ear edge vein is taken a blood sample once more and is measured above-mentioned five indices, calculates the Tc/HDL value, and three measurement results are divided into groups to carry out statistical disposition respectively, detects with t, and relatively each group has there was no significant difference.
3.6 experimental result: see Table 1～table 5.
Table 1 is irritated stomach XSL and LSL medicated powder January to the influence of rabbit blood T-CHOL (TC) (x ± SD)
| Group | Dosage (g/kg) | Number of animals (only) | Before the moulding (mmol/L) | Moulding January (mmol/L) | Administration January (mmol/L) |
| Blank model group Lovastatin XSL LSL | Distilled water distilled water 8mg/kg 0.2 0.6 1.2 0.2 0.6 1.2 | 8 8 8 8 8 8 8 8 8 | 1.50±0.55 1.65±0.55 1.45±0.86 1.68±0.68 1.66±0.52 1.88±0.66 1.64±0.54 1.72±0.62 1.60±0.75 | 1.63±0.50 6.53±3.20 ** 6.71±2.19 ** 6.93±3.17 ** 6.31±3.00 ** 6.32±1.98 ** 6.93±2.57 ** 6.38±3.08 ** 5.96±2.88 ** | 1.50±0.34 13.39±3.20 **◆ 2.40±0.51 △△◆ 3.69±2.42 △△◆ 3.11±2.85 △△◆ 2.60±1.76 △△◆ 6.85±4.36 △△ 5.81±3.00 △△ 5 .72±1.98 △△ |
Annotate:
*Compare p＜0.01 with the blank group;
△ △Compare p＜0.01 with model group.
◆Compare P＜0.05 January on the same group with moulding
Table 2 is irritated stomach XSL and LSL medicated powder January to the influence of rabbit triglyceride (TG) (x ± SD)
| Group | Dosage (g/kg) | Number of animals (only) | Before the moulding (mmol/L) | Moulding January (mmol/L) | Administration January (mmol/L) |
| Blank model group Lovastatin XSL LSL | Distilled water distilled water 8mg/kg 0.2 0.6 1.2 0.2 0.6 1.2 | 8 8 8 8 8 8 8 8 8 | 1.06±0.27 0.83±0.31 1.05±0.44 1.34±0.61 1.04±0.28 1.20±0.64 1.29±0.43 1.12±0.38 1.25±0.46 | 1.06±0.36 1.88±0.71 * 1.77±0.71 * 1.89±0.73 * 1.78±0.71 * 1.68±0.49 * 1.90±0.43 * 1.80±0.34 * 1.76±0.27 * | 0.96±0.40 2.14±1.15 * 0.51±0.15 △△◆ 0.80±0.32 △△◆ 0.57±0.43 △△◆ 0.54±0.14 △△◆ 1.71±0.45 △△ 1.64±0.35 △△ 1.58±0.26 △△ |
Annotate:
*Compare p＜0.05 with the blank group.
△ △Compare p＜0.01 with model group
◆Compare P＜0.05 January on the same group with moulding
Table 3-irritates stomach XSL and LSL medicated powder January to the influence of rabbit high density lipoprotein (HDL) (x ± SD)
| Group | Dosage (g/kg) | Number of animals (only) | Before the moulding (mmol/L) | Moulding January (mmol/L) | Administration January (mmol/L) |
| Blank model group Lovastatin XSL LSL | Distilled water distilled water 8mg/kg 0.2 0.6 1.2 0.2 0.6 1.2 | 8 8 8 8 8 8 8 8 8 | 0.37±0.18 0.38±0.10 0.32±0.14 0.41±0.17 0.39±0.18 0.41±0.16 0.37±0.11 0.36±0.11 0.38±0.12 | 0.38±0.07 1.04±0.24 ** 0.96±0.13 ** 0.89±0.39 ** 0.93±0.29 ** 1.00±0.19 ** 0.98±0.18 ** 0.93±0.14 ** 0.95±0.16 ** | 0.39±0.15 1.00±0.30 ** 1.41±0.27 △◆ 1.01±0.24 ◆ 1.29±0.36 ◆ 1.36±0.33 △◆ 1.06±0.18 1.00±0.15 1.02±0.17 △ |
Annotate:
*Compare p＜0.01 with the blank group;
△Compare p＜0.05 with model group;
△ △Compare p＜0.01 with model group
◆Compare P＜0.05 January on the same group with moulding.
Table 4 is irritated stomach XSL and LSL medicated powder January to the influence of rabbit low density lipoprotein, LDL (LDL) (x ± SD)
| Group | Dosage (g/kg) | Number of animals (only) | Before the moulding (mmol/L) | Moulding January (mmol/L) | Administration January (mmol/L) |
| Blank model group Lovastatin XSL LSL | Distilled water distilled water 8mg/kg 0.2 0.6 1.2 0.2 0.6 1.2 | 8 8 8 8 8 8 8 8 8 | 0.70±0.47 0.86±0.50 0.92±0.79 0.91±0.44 0.80±0.49 0.93±0.54 0.76±0.23 0.80±0.25 0.82±0.28 | 0.72±0.05 4.35±3.53 ** 3.73±2.72 ** 3.89±2.58 ** 4.44±2.3 ** 3.73±1.62 ** 4.10±2.42 ** 4.15±1.78 ** 3.93±1.16 ** | 0.71±0.20 11.47±3.00 ** 0.76±0.33 △△◆ 3.35±2.30 △△◆ 3.11±2.40 △△◆ 1.97±1.71 △△◆ 3.63±2.12 △△ 3.40±1.62 △△ 3.07±1.83 △△ |
Annotate:
*Compare p＜0.01 with the blank group;
△ △Compare p＜0.01 with model group.
◆Compare P＜0.05 January on the same group with moulding.
Table 5 is irritated stomach XSL and LSL medicated powder January to the influence of rabbit very low density lipoprotein (VLDL) (VLDL) (x ± SD)
| Group | Dosage (g/kg) | Number of animals (only) | Before the moulding (mmol/L) | Moulding January (mmol/L) | Administration January (mmol/L) |
| Blank model group Lovastatin XSL LSL | Distilled water distilled water 8mg/kg 0.2 0.6 1.2 0.2 0.6 1.2 | 8 8 8 8 8 8 8 8 8 | 0.46±0.11 0.38±0.14 0.48±0.20 0.43±0.16 0.47±0.13 0.55±0.29 0.51±0.14 0.50±0.12 0.47±0.10 | 0.48±0.16 0.83±0.32 * 0.81±0.33 * 0.86±0.33 * 0.81±0.32 * 0.74±0.21 * 0.81±0.13 * 0.84±0.20 * 0.86±0.14 * | 0.41±0.13 0.80±0.26 ** 0.24±0.07 △△◆ 0.33±0.18 △△◆ 0.26±0.19 △△◆ 0.27±0.11 △△◆ 0.73±0.15 0.71±0.18 0.74±0.12 |
Annotate:
*Compare p＜0.05 with the blank group;
*Compare p＜0.01 with the blank group;
△ △Compare p＜0.01 with model group
◆Compare P＜0.05 January on the same group with moulding.
Shown in table 1～table 5: clothes fat is respectively organized the equal no difference of science of statistics of the every index of blood fat before the meal.Rabbit is through feeding high lipid food January, and five of high fat treated animals detect index and obviously raise, with blank group comparing difference highly significant, p＜0.05 and p＜0.01, and the hyperlipidemia model success.After administration January, the effect for reducing fat highly significant of positive drug lovastatin 8mg/kg, it is normal that every index is all recovered.The hyperlipemia rabbit is through irritating stomach XSL medicine 0.2g, 0.6g and 1.2g medicated powder/kg January, can not only suppress blood fat continues to raise, and has a blood fat reducing effect, blood fat T-CHOL, triglyceride, low density lipoprotein, LDL and the very low density lipoprotein (VLDL) of three dosage groups compares with model group respectively, obviously reduce, detect p＜0.01 through t; High density lipoprotein all increases to some extent; In addition. the hyperlipemia rabbit can suppress blood fat and continue to raise, but the blood fat reducing effect is not obvious through irritating stomach LSL medicine 0.2g, 0.6g and 1.2g medicated powder/kg January.
3.7 conclusion
3.7.1 having the rabbit of inhibition blood fat, medicine of the present invention raises and the blood fat reducing effect.
3.7.2 patent 95108297.3 medicines have prevention rabbit blood fat rising effect.
More than test confirms medicine of the present invention medicine in the excellent sub-patent 95108297.3 aspect treatment and prevention hyperlipidemia.
4, clinical experiment
4.1 clinical settings
SONGLING XUEMAIKANG JIAONANG (medicine of the present invention) is the Chinese medicine of the treatment hyperlipemia of Chengdu Kanghong Pharmaceutical Co., Ltd's development.According to the 2001ZL027 of National Drug Administration certification in April calendar year 2001 to calendar year 2001 JIUYUE in Dongzhimen Hospital, Beijing Univ of Traditional Chinese Medicine, Guang-amen Hospital, China Traditional Chinese Medicine Instl, Hospital No.1 Attached to Tianjin Traditional Chinese Medicine College, Second Hospital Attached To Tianjin Chinese Medicine College has carried out the clinical trial of SONGLING XUEMAIKANG JIAONANG, adopt the method for randomized, double-blind dual analog controlled trial that it has been carried out the II clinical trial phase, investigate its blood fat reducing curative effect and untoward reaction.Four tame hospitals include case 208 examples altogether in, reject (coming off) 3 examples, and 103 examples are organized in treatment, matched group 102 examples.Clinical test results is as follows: two groups of medicine blood fat reducing determined curative effects, wherein treatment group (new drug of the present invention) blood fat reducing efficacy determination clinic control 12 examples, produce effects 30 examples, effective 39 examples, it is 40.8% that control shows rate, total effective rate is 78.6%, tcm syndrome clinic control 5 examples, produce effects 29 examples, effective 53 examples, it is 33.0% that control shows rate, and total effective rate is 84.5%, compares with matched group Herb Gynostemmae Pentaphylli general glycoside, blood fat reducing curative effect and tcm syndrome curative effect all are better than matched group, blood fat curative effect P＞0.05 wherein, the difference nonsignificance, and tcm syndrome curative effect and tcm syndrome integration are relatively, P between group＜0.05, point out medicine of the present invention aspect the improving of tcm syndrome, effect is better than matched group, has no side effect in therapeutic process and untoward reaction simultaneously.
4.2 physical data
4.2.1 case source:
Select outpatient service and inpatient totally 205 examples, wherein inpatient 37 examples account for 18.05%, and out-patient's 168 examples account for 81.95%, and all case all meets the case choice criteria.
Treatment is organized among the 103 routine patients, hypercholesterolemia (TC) mass formed by blood stasis 26 examples, high triglyceride (TG) mass formed by blood stasis 31 examples, combined hyperlipidemia familial 41 examples, high density lipoprotein deficiency (HDL) 5 examples.
Among the matched group 102 routine patients, hypercholesterolemia (TC) mass formed by blood stasis 37 examples, high triglyceride (TG) mass formed by blood stasis 31 examples, combined hyperlipidemia familial 32 examples, high density lipoprotein deficiency (HDL) 2 examples.
4.2.2 sex: two groups of patient's sex ratios see Table 1.
Table 1 liang group patient sex ratio
| Group | The example number | Man (%) | Woman (%) | Man: woman |
| Treatment group matched group | 103 102 | 56(54.4) 52(51.0) | 47(45.6) 50(49.0) | 56∶47 52∶50 |
X
2＝0.120 P＝0.729
Two groups of patient's sexes are formed relatively, P＞0.05, and the difference nonsignificance has comparability.
4.2.3 the age: two groups of patient ages distribute relatively, see Table 2.
Table 2 a liang group patient age distributes and compares (example)
| Group | The example number | 18 years old～(%) | 31 years old～(%) | 41～(％) | 51～65 years old (%) | Mean age (x ± s) | min | max |
| Treatment group matched group | 103 102 | 3(2.9) 1(1.0) | 13(12.6) 16(15.7) | 33(32.0) 31(30.4) | 54(52.4) 54(52.9) | 50.660±9.270 51.147±9.210 | 24 28 | 65 65 |
X
2＝1.368 P＝0.713
Minimum 24 years old of the age in the treatment group, maximum 65 years old age; Minimum 28 years old of matched group age, maximum 65 years old age; Two groups of patient ages compositions are compared, P＞0.05, and the difference nonsignificance has comparability.
4.2.4 the course of disease: two groups of patient's courses of disease distribute relatively, see Table 3.
Table 3 a liang group patient course of disease distributes and compares (example)
| Group | The example number | ＜1 year (%) | 1 year～(%) | 5 years～(%) | 10 years～(%) | Average course of disease (x ± s) | min | max |
| Treatment group matched group | 103 102 | 14(13.6) 16(15.7) | 69(67.0) 66(64.7) | 13(12.6) 12(11.8) | 7(6.8) 8(7.8) | 2.867±3.050 2.931±2.958 | 0.1 0.1 | 20 15 |
X
2＝0.302 P＝0.960
The treatment group patient course of disease is the shortest 0.1 year, and is the longest 20 years; The matched group patient course of disease is the shortest 0.1 year, and is the longest 15 years; Two groups of patient's courses of disease distribute relatively, P＞0.05, and the difference nonsignificance has comparability.
4.2.5 the state of an illness: two groups of patient's traditional Chinese medical science state of an illness relatively see Table 4.
The table 4 liang group patient traditional Chinese medical science state of an illness relatively
| Group | The example number | Slightly (%) | Moderate (%) | Severe (%) |
| Treatment group matched group | 103 102 | 19(18.4) 21(20.6) | 71(68.9) 72(70.6) | 13(12.6) 9(8.8) |
X
2＝0.808 P＝0.668
Treat preceding two groups of patient's traditional Chinese medical science state of an illness relatively, P＞0.05, the difference nonsignificance has comparability.
4.2.6 tcm symptom: tcm symptom relatively sees Table 5 before two groups of patient treatments.
Tcm symptom relatively before the table 5 liang group patient treatment
| Symptom | Treatment group (N=103) | Matched group (N=102) | Compare between group | |||||||||
| The example number | - | + | ++ | +++ | The example number | - | + | ++ | +++ | X 2 | P | |
| Dizziness and headache palpitation and insomnia being irritable and getting angry easily | 103 103 103 103 103 | 3 11 25 31 25 | 38 62 46 53 34 | 57 30 31 17 41 | 5 0 1 2 3 | 102 102 102 102 102 | 7 12 32 37 25 | 41 61 36 44 39 | 45 29 34 18 28 | 9 0 0 3 10 | 4.264 0.212 3.213 0.968 6.556 | 0.234 0.900 0.360 0.809 0.087 |
Treat preceding two groups of patient's tcm symptoms relatively, P＞0.05, the difference nonsignificance has comparability.
4.2.7 the hyperlipemia type relatively sees Table 6 before two groups of patient treatments.
The hyperlipemia type relatively before the table 6 liang group patient treatment
| Project | Treatment group (%) | Matched group (%) | Compare between group | |
| X 2 | P | |||
| Hypercholesterolemia hypertriglyceridemia mixed type lipidemia low hdl mass formed by blood stasis | 26(25.2) 31(30.1) 41(39.8) 5(4.9) | 37(36.3) 31(30.4) 32(31.4) 2(2.0) | 2.589 0.004 1.132 0.552 | 0.108 0.952 0.287 0.664 |
Treat preceding two groups of patient's blood fat types relatively, P＞0.05, the difference nonsignificance has comparability.
4.2.8 the blood fat situation relatively sees Table 7 before two groups of patient treatments.
The blood fat situation compares (mmol/L) before the table 7 liang group patient treatment
| Project | Group | The example number | Meansigma methods (x ± s) | t | p |
| TC TG HDL-C LDL-C TC-HDL-C/ HDL-C APOA APOB APOA/APOB | Treatment group treatment of control group group treatment of control group group treatment of control group group treatment of control group group treatment of control group group treatment of control group group treatment of control group group control group | 103 102 103 102 103 102 103 102 103 102 53 52 53 52 53 52 | 5.990±0.924 5.958±1.061 2.810±1.300 2.594±1.087 1.271±0.354 1.337±0.412 3.564±0.950 3.409±1.088 4.010±1.372 3.795±1.579 1.313±0.156 1.266±0.197 1.117±0.230 1.068±0.243 1.237±0.365 1.253±0.266 | 0.285 1.289 -1.233 1.088 1.038 1.370 1.058 -0.215 | 0.791 0.199 0.219 0.278 0.301 0.174 0.292 0.830 |
Treat preceding two groups of patient's blood fat situations relatively, P＞0.05 difference nonsignificance has comparability.
4.3 case is selected
4.3.1 diagnostic criteria:
4.3.1.1 diagnostic criteria: with reference to " the clinical research guideline of new Chinese medicine treatment hyperlipemia " and Chinese cardiovascular diseases's magazine editorial board's cardiovascular drugs countermeasure special topic group " suggestion of cardiovascular drugs clinical trial evaluation methodology " in 1998 formulation.
(1) Western medicine diagnose standard:
Hyperlipemia: under the normal diet situation, survey serum total cholesterol (TC) 〉=5.72mmol/L (220mg/dl) or triglyceride (TG) 〉=2.26mmol/L (200mg/dl) or high density lipoprotein (HDL-C)≤1.04mmol/L (40mg/dl) (men and women is identical) person as 2 times in 2 weeks, promptly diagnosable.
(annotate: clinical trial case uniform requirement calculates with mmol/L unit)
(2) Chinese medical discrimination and syndrome criterion:
Syndrome of upper hyperactivity of liver yang: dizzy, headache, being irritable and getting angry easily, cardiopalmus, insomnia, red tongue, stringy pulse or count accurately, main symptom possesses one, and inferior card is more than one, in conjunction with the tongue arteries and veins.
4.3.1.2 tcm syndrome scoring method:
Dizzy: 0 minute (-): normal
2 minutes (+): conscious having a dizzy spell, sense of rotation or the rolling of not having self or scenery are dynamic; Or simple head is murky and do not influence activity.
4 minutes (++): conscious dizziness also has self or the sense of rotation of scenery or rolling innervation, but does not influence activity; Or simple giddy and influence activity, but can adhere to work.
6 minutes (+++): conscious dizziness also has self or the sense of rotation of scenery, and a body dare not rotate; Or simple dizzy, upset, be difficult to competent at a job.
Headache: 0 minute (-): normal
2 minutes (+): little sense headache.
4 minutes (++): it is heavier to have a headache, but does not influence orthobiosis and work.
6 minutes (+++): headache is heavy, influences live and work.
Cardiopalmus: 0 minute (-): normal
1 minute (+): random thoughts cardiopalmus, but spontaneous remission.
2 minutes (++): it is more frequent that palpitation of the heart comes on, but do not influence orthobiosis and work.
3 minutes (+++): cardiopalmus continues not understand, and influences live and work.
Insomnia:
-0 minute (-): normal
1 minute (+): difficulty falling asleep, do not have enough sleep every day 5 hours.
2 minutes (++): do not have enough sleep 4 hours, and still can adhere to work and life.
3 minutes (+++): do not have enough sleep 4 hours, and influenced work and life.
Body of the tongue: 0 minute (-): normal body of the tongue
1 minute (+): the body of the tongue color is red
Pulse condition: 0 minute (-): other pulse conditions.
1 minute (+): string or count accurately.
4.3.2 include the case standard in:
4.3.2.1 men and women between 18～65 years old age.
4.3.2.2 meet diagnostic criteria of doctor trained in Western medicine hyperlipemia and Chinese medical discrimination syndrome of upper hyperactivity of liver yang person.
4.3.2.3 signature Informed Consent Form.
4.3.3 get rid of the case standard:
4.3.3.1 the age is at under-18s or over-65s, gestation or women breast-feeding their children, allergic constitution person, and drug allergy patient.
4.3.3.2 once suffered from acute myocardial infarction in half a year, cerebrovascular accident, seriously the creation or capital operation after the patient.
4.3.3.3 because of the hyperlipemia due to nephrotic syndrome, hypothyroidism, gout, acute or chronic liver and gall diseases, the diabetes etc.
4.3.3.4 by medicine (phenothiazines, beta-Blocking agent, adrenocortical steroid and some contraceptive etc.) hyperlipemia that causes and the subtype high-cholesterol disease patient of isozygotying.
4.3.3.5 using heparin, thyroxine therapy medicine and other to influence the patient of blood metabolic drug, and the patient who nearly 2 weeks once adopted other blood fat reducing measures.
4.3.3.6 merge serious primary disease such as liver, kidney and hemopoietic system, psychotic.
4.3.3.7 participate in the patient of other clinical trials.
4.4 test method
4.4.1 group technology:
4.4.1.1II clinical trial phase is a multiple center trial, carries out simultaneously in 4 tame hospitals.Adopt the test method of randomized, double-blind dual analog contrast.Each 100 example of treatment group and matched group are carried out experimental control in 1: 1 ratio.
(1) enforcement of blind method:
Though because treatment group SONGLING XUEMAIKANG JIAONANG is consistent with the capsular dosage form of matched group Herb Gynostemmae Pentaphylli general glycoside, capsule outward appearance, color and not of uniform size causing are so this test intended is taked the method for randomized, double-blind dual analog contrast.Utilization Sun Ruiyuan professor's NDST statistical software is in the case allotment of participant and ratio generation table of random number at random.
(2) make the SONGLING XUEMAIKANG JIAONANG placebo, its outward appearance, shape, color are basic consistent with SONGLING XUEMAIKANG JIAONANG.Herb Gynostemmae Pentaphylli general glycoside capsule placebo, its outward appearance, shape, color are basic consistent with Herb Gynostemmae Pentaphylli general glycoside capsule.
(3) the SONGLING XUEMAIKANG JIAONANG placebo is adopted the outer package identical with SONGLING XUEMAIKANG JIAONANG; Herb Gynostemmae Pentaphylli general glycoside capsule placebo is adopted and the identical outer package of Herb Gynostemmae Pentaphylli general glycoside capsule.
(4) each experimenter's pharmaceutical pack is dressed up 1 part, and dated code.
Per 1 part of medicated bag is drawn together: SONGLING XUEMAIKANG JIAONANG+Herb Gynostemmae Pentaphylli general glycoside capsule placebo
Or Herb Gynostemmae Pentaphylli general glycoside capsule+SONGLING XUEMAIKANG JIAONANG placebo
(5), each part trial drug is carried out random number, and indicate in packaging bag according to table of random number.Researcher fills in random number on the medical history record table according to the order of subject enrollment, and the test drug identical with random number provided in the notice pharmacy.
4.4.2 test medication:
The treatment group: SONGLING XUEMAIKANG JIAONANG, each 3, every day 3 times, (this medicine is provided by Chengdu Kanghong Pharmaceutical Co., Ltd warm water delivery service, lot number: 010301) after meal.Take Herb Gynostemmae Pentaphylli general glycoside capsule placebo simultaneously, each 1, every day 3 times, warm water delivery service (providing) after meal by Chengdu Kanghong Pharmaceutical Co., Ltd.
Matched group: (this medicine provides lot number by safe and comfortable Beijing Medical University Pharmacy stock Co., Ltd to Herb Gynostemmae Pentaphylli general glycoside capsule: 20000604).Each 1, every day 3 times, warm water delivery service after meal.Take the SONGLING XUEMAIKANG JIAONANG placebo simultaneously, each 3, every day 3 times, warm water delivery service (this medicine is provided by Chengdu Kanghong Pharmaceutical Co., Ltd) after meal.
Annotate: test preceding 1 month, duration of test and avoid using the medicine that influences lipid metabolism.
4.4.3 the course of treatment: 4 weeks.
4.4.4 test routine number: 103 examples are organized in treatment, matched group 102 examples.
4.4.5 observation index:
4.4.5.1 safety detects:
(1) general health check-up project: blood pressure, heart rate, the rhythm of the heart
(2) blood, urine, just routine examination
(3) electrocardiogram, liver (ALT), kidney (Cr BUN) functional check
4.4.5.2 health giving quality observation:
(1) related symptoms and sign.
(2) body weight (2 times)
(3) before the treatment, treatment back T-CHOL (TC), triglyceride (TG), high density lipoprotein (HDL-C), low density lipoprotein, LDL (LDL-C), very low density lipoprotein (VLDL) (VLDL-C), T-CHOL one high density lipoprotein/high density lipoprotein (TC-HDL-C/HDL-C) lipids contents are measured.
-(4) apolipoprotein is measured (APO-AI, APO-B100), is finished by Dongzhimen Hospital, Beijing Univ of Traditional Chinese Medicine and Second Hospital Attached To Tianjin Chinese Medicine College.
4.4.6 lipid determination method and quality control way;
4.4.6.1 observation index and method: the method that the suggestion of lipid determination method can be recommended with Chinese Medical Association's ecsomatics.
Detect the test kit that TC, TG produce with Beijing Zhongsheng Biological Engineering High Technology Company.
T-CHOL is measured: enzyme process (CHOD-PAP method)
Triglyceride determination: enzyme process (GPO-PAP method)
Determine cholesterol with high density lipoprotein: phosphotungstic acid magnesium (PTA-Mg2+) sedimentation method.
Low-density lipoprotein cholesterol is measured: polyvinyl sulfuric acid (PVS) step sedimentation method.
Apolipoprotein is measured: phototurbidometry
4.4.6.2 the quality control of biochemical investigation:
The project of clinical biochemical check is increasing, and used instrument is accurate day by day, and complicated and various, varieties of reagent is various, and is diversified in specifications, thereby holds gate of the quality monitoring, and it is very important to carry out Quality Control work.
For making measurement result accurate, need set up rule of operation and operation sheet, and use " multinomial quality controlled serum " that Beijing Zhongsheng Biological Engineering High Technology Company provides, be used for the indoor quality control of clinical biochemical check, be responsible for by the special messenger, set up quality control chart.Operate the computer simultaneously with quality controlled serum when each specimen is measured, test result must not exceed 1.5-2SD (standard deviation), if exceeding this scope then conscientiously searches reason, operates again, makes every effort to the reliability of measurement result.
For making measurement result accurately and reliably, noted following a few part in the detection:
(1) sampling: empty stomach is the daystart vein haemospasia after 12 hours.
(2) at least 2 weeks of diet that should keep original rule before the blood sampling, and keep body weight constant.
(3) clinical trial should in the same period be carried out, the error of bringing to measurement to reduce season.
(4) operate: quality controlled serum and reagent matching while using, application of sample is wanted accurately, and Quality Control numerical value does not exceed 1.5SD-2SD, allows operation normally to carry out, and writes down each Quality Control data, and the Quality Control figure that draws, the end of the month are added up, and calculate the CV value, must be less than 3%.
(5) set up and adhere to indoor Quality Control, or participate in national or provincialism Quality Control activity.
(6) control between the chamber: for reducing the measurement error between the chamber, preferably unify reagent (same producer), same quality controlled serum, to observe the measurement gap between each chamber, instrument is difficult for unified, but must maintain optimum state.Often carry out the self-aligning of instrument.
4.4.7 efficacy determination
Formulate with reference to " new Chinese medicine treatment hyperlipemia clinical research guideline ".
4.4.7.1 blood fat curative effect determinate standard;
(1) clinic control: treatment back lipids detection recovers normal.
(2) produce effects: treat the back lipids detection and reach following any one person:
TC decline 〉=20% TG decline 〉=40% HDL-C rising 〉=0.26mmol/L (10mg/dl)
TC-HDL-C/HDL-C/ descends 〉=20%
(3) effective: lipid examination reaches following any one person;
TC descend 〉=10% but＜20% TG descend 〉=20% but＜40% HDL-C risings 〉=0.103mml/dl (4mg/dl), but＜0.26mmol/L (10mg/dl), TC-HDL-C/HDL-C decline 〉=10%, but＜20%
(4) invalid: treatment back lipid examination does not have obvious improvement or improvement does not reach effective standard person.
4.4.7.2 tcm syndrome total effects criterion:
Judge the tcm syndrome total effects according to integration method.
(1) clinical recovery: clinical symptoms, sign integration improve 〉=90%
(2) produce effects: clinical symptoms, sign integration improve 〉=70%＜90%.
(3) effective: clinical symptoms, sign integration improve 〉=30%＜70%.
(4) invalid: clinical symptoms, sign integration improve＜30%.
4.4.7.3 individual event symptom efficacy assessment standard:
(1) clinical recovery: transference cure.
(2) produce effects: symptom is clearly better, by +++→+.
(3) effective: symptom takes a turn for the better, by +++→ ++, or ++ →+.
(4) invalid: symptom does not have change, or alleviates not obvious.
4.4.8 safety evaluatio standard:
1 grade: safety, there is not any untoward reaction; Safety indexes is checked no abnormal.
2 grades: compare safety, mild adverse effects is arranged, need not do any processing and can continue administration, safety indexes is checked no abnormal.
3 grades: safety issue is arranged, moderate untoward reaction is arranged, or the safety indexes inspection has mile abnormality, can continue administration after processing.
4 grades: because of serious adverse reaction is ended test; Or the safety indexes inspection is obviously unusual.
4.4.9 end and remove the standard of clinical trial:
4.4.9.1 the reason that the doctor who participates in clinical trial ends test with and with the relation of test as conscientious record how, comprise the evaluation when ending.
(1) can not adhere to therapist.
(2) patient of serious adverse reaction appears.
(3) other serious concurrent disease patient appears in the process of the test.
(4) sx, must the person of taking urgent measure.
4.4.9.2 will clearly write down reason, and the index estimated when ending of itemized record to the patient who proposes to withdraw from test by the patient midway.
(1) patient proposes to withdraw from test.
(2) patient's institute's further consultation that do not come in time is answered inquiry reasons such as phone, mail and is investigated the process of thing.
(3) other.
4.4.9.3 case is rejected principle
(1) natural seceder in the observation.
(2) it is effective to take this medicine, but the patient takes other close medicine for quickening curative effect, can't judge curative effect.
(3) the last diagnostic person that do not meet the assertive evidence.
(4) take medicine and 3 weeks above invalidly stopped using or change other close medicine, should must not reject by invalidation.
(5) can not adhere to treatment and end test or can not finish one-hundred-percent inspection observation item case for some reason for some reason.
4.4.10 the record of untoward reaction and method for reporting:
To the untoward reaction that duration of test occurs, should be with its symptom, degree, time of occurrence, persistent period, treatment measures, pass through etc. are recorded in the observation table, and taking all factors into consideration complication, on the drug combination basis, estimate the dependency of itself and trial drug, and by doctor's itemized record.
In addition, when finding untoward reaction, observe the doctor and can whether end to observe, should carry out follow up survey to case, its result of itemized record because of the untoward reaction drug withdrawal according to state of an illness decision.
In test as serious adverse events occurs, researcher should adopt suitable protective measure to the experimenter immediately, and 24 in hour report medicine management department, bidding person and Ethics Committee, researcher will be signed in report and date.
4.4.11 collection of data and statistical method
4.4.11.1 case is checked and accepted: strict and carry out clinical position, check and accept case and must not lack a perforated scrofula of neck and make summary table so that statistics by scheme.
4.4.11.2 for not medication in accordance with regulations, can't judge curative effect, or data is not congruent affects the treatment or safe judgement person, rejected, reject case and should describe reason in detail.
4.4.11.3 the statistical disposition of clinical data:
Adopt Sun Ruiyuan professor NDST statistical software:
(1) ranked data are checked with Ridit
(2) enumeration data X 2 test
(3) measurement data is checked with t
4.4.11.4 statistical requirements
(1) balanced measurement between group before the treatment.
Curative effect statistics and remarkable meaning are measured between (2) two groups.
(3) dependency statistics.
4.4.12 broken blind method
Randomized, double-blind dual analog test method is taked in this clinical trial, takes " secondary broken blind " mode: it is broken blind to carry out first time after patient is all over the course of treatment, promptly whole patients' grouping break blindly, is divided into that A organizes and B organizes; It is broken blind to carry out second time after statistical procedures finishes, and promptly A group and B being organized is that treatment group or matched group are taken off blind.
4.5 therapeutic outcome
4.5.1 the blood fat total effects relatively sees Table 8 behind two groups of patient treatments.
The blood fat total effects compares (example) behind the table 8 liang group patient treatment
| Group | The example number | Clinic control N (%) | Produce effects N (%) | Effective N (%) | Invalid N (%) | Control shows rate % | Total effective rate % |
| Treatment group matched group | 103 102 | 12(11.7) 9(8.8) | 30(29.1) 21(20.6) | 39(37.9) 44(43.1) | 22(21.4) 28(27.5) | 40.8 29.4 | 78.6 72.5 |
Ridit analyzes: treatment group and matched group compare: U=1.566 P＞0.05
Compare between the curative effect group behind two groups of patient treatments.Treatment group curative effect is better than matched group, but P＞0.05, the difference nonsignificance.
4.5.2 two groups of dissimilar hyperlipemia blood fat curative effects relatively, sees Table 9.
The table 9 liang dissimilar hyperlipemia blood fat curative effects of group are (example) relatively
| Project | Group | The example number | Clinic control N (%) | Produce effects N (%) | Effective N (%) | Invalid N (%) | Control shows rate % | Total effective rate % |
| The simple low HDL disease of the high TG disease of high TC disease mixed type pionemia | Treatment group treatment of control group group treatment of control group group treatment of control group group control group | 26 37 31 31 41 32 5 2 | 6(23.1) 4(10.8) 5(16.1) 3(9.7) 1(2.4) 2(6.3) 0 0 | 7(26.9)) 4(10.8) 6(19.4) 5(16.1) 16(39.6) 11(34.4) 1(20.0) 1(50.0) | 6(23.1) 18(48.6) 13(41.9) 13(41.9) 18(43.9) 12(37.5) 2(40.0) 1(50.0) | 7(26.9) 11(29.7) 7(22.6) 10(32.3) 6(14.6) 7(21.9) 2(40.0) 0 | 50.0 21.6 35.5 25.8 41.5 40.6 20.0 50.0 | 73.1 70.3 77.4 67.7 85.4 78.1 60.0 100.0 |
Ridit analyzes: treatment group and matched group compare:
High TC disease: U=1.491 P＞0.05
High TG disease: U=0.969 P＞0.05
Mixed type lipidemia: U=0.224 P＞0.05
Simple low HDL-C mass formed by blood stasis: U=1.044 P＞0.05
Various hyperlipemia is through after treating, and two groups are relatively, and treatment group curative effect all is better than matched group, but P＞0.05, the difference nonsignificance.
4.5.3 blood lipid level relatively sees Table 10 before and after two groups of patient treatments.
Blood lipid level compares (mmol/L) before and after the table 10 liang group patient treatment
| Project | Group | The example number | X ± s before treating | Treat back x ± s | Difference x ± s | Self relatively | Compare between group | ||
| t | P | t | P | ||||||
| TC TG HDL-c LDL-c TC-HDL-c/H DL-c APOA APOB APOA/APOB | Treatment group treatment of control group group treatment of control group group treatment of control group group treatment of control group group treatment of control group group treatment of control group group treatment of control group group control group | 103 102 103 102 103 102 103 102 103 102 53 52 53 52 53 52 | 5.990±0.924 5.958±1.061 2.810±1.300 2.594±1.087 1.271±0.354 1.337±0.412 3.564±0.950 3.409±1.088 4.010±1.372 3.795±1.579 1.313±0.156 1.266±0.197 1.117±0.230 1.068±0.243 1.237±0.365 1.253±0.266 | 5.497±0.780 5.594±0.810 2.069±0.773 2.214±1.184 1.342±0.366 1.354±0.327 3.291±0.975 3.317±0.897 3.371±1.305 3.302±0.981 1.355±0.175 1.253±0.204 1.097±0.260 1.038±0.253 1.311±0.398 1.304±0.373 | 0.498±0.635 0.364±0.756 0.741±1.044 0.380±1.000 0.071±0.194 0.017±0.270 0.273±0.671 0.092±0.711 0.640±0.886 0.493±1.314 -0.004±0.121 -0.040±0.105 -0.020±0.115 0.030±0.118 0.050±0.170 0.034±0.179 | 7.958 4.867 7.023 3.839 -3.731 -0.641 4.142 1.313 7.317 3.793 -2.641 -1.082 1.253 1.829 -3.340 -2.134 | 0.000 0.000 0.000 0.000 0.000 0.523 0.000 0.192 0.000 0.000 0.011 0.285 0.216 0.073 0.002 0.038 | 1.375 2.525 1.650 1.875 0.933 1.635 -0.447 0.480 | 0.171 0.012 0.101 0.062 0.352 0.105 0.656 0.632 |
4.5.3.1 treatment group TC, TG, HDL-c, LDL-c, TC-HDL-c/HDL-c, APOA, APOA/APOB self are relatively before and after two groups of patient treatments, be P＜0.05, the difference significance, matched group TC, TG, TC-HDL-c/HDL-c, APOA/APOB self are relatively, also be P＜0.05, the difference significance.
4.5.3.2 the blood fat and improving degree compares before and after two groups of patient treatments, removes between the TG group and compares P＜0.05, treatment group decline degree outside the more remarkable treatment effect, compares P＞0.05, difference nonsignificance between all the other groups greater than matched group.
4.5.4 the TC curative effect relatively saw Table 11 before and after the cholesterol person of increasing treated before two groups of patients treated.
The TC curative effect relatively before and after the cholesterol person of increasing treated before table 11 a liang group patient treated
| Group | The example number | X ± s before treating | Treat back x ± s | Difference x ± s | Self relatively | Compare between group | ||
| t | P | t | P | |||||
| Treatment group matched group | 67 69 | 6.545±0.555 6.532±0.669 | 5.832±0.711 5.917±0.647 | 0.793±0.646 0.615±0.679 | 9.033 7.519 | 0.000 0.000 | 0.865 | 0.388 |
4.5.4.1 TC value self relatively is P＜0.01 before and after two groups of patient treatments, difference has extremely significantly meaning.
4.5.4.2 the TC curative effect compares before and after two groups of patient treatments, P between group＞0.05, and the difference nonsignificance, two groups of curative effects are close.
4.5.5 the TG curative effect relatively saw Table 12 before and after the triglyceride person of increasing treated before two groups of patients treated.
The TG curative effect relatively before and after the triglyceride person of increasing treated before table 12 a liang group patient treated
| Group | The example number | X ± s before treating | Treat back x ± s | Difference x ± s | Self relatively | Compare between group | ||
| t | P | t | P | |||||
| Treatment group matched group | 72 63 | 3.328±1.189 3.168±0.969 | 2.323±0.701 2.529±0.984 | 1.005±1.110 0.639±0.654 | 7.678 7.757 | 0.000 0.000 | 2.368 | 0.020 |
4.5.5.1 self relatively is P＜0.01 before and after two groups of patient treatments, difference has extremely significantly meaning.
4.5.5.2 the TG curative effect compares before and after two groups of patient treatments, P between group＜0.05, and the difference significance, the treatment group is better than matched group.
4.5.6 the HDL curative effect relatively saw Table 13 before and after the low person of HDL treated before two groups of patients treated.
The HDL curative effect relatively before and after the low person of HDL treated before table 13 a liang group patient treated
| Group | The example number | X ± s before treating | Treat back x ± s | Difference x ± s | Self relatively | Compare between group | ||
| t | P | t | P | |||||
| Treatment group matched group | 32 29 | 0.936±0.103 0.929±0.108 | 1.054±0.182 1.104±0.196 | 0.118±0.177 0.175±0.245 | -3.763 -3.837 | 0.001 0.001 | -1.031 | 0.307 |
4.5.6.1 self relatively is P＜0.01 before and after two groups of patient treatments, difference has extremely significantly meaning.
4.5.6.2 compare between the HDL group before and after two groups of patient treatments, P＞0.05, the difference nonsignificance, two groups of curative effects are close.
4.5.7 two groups of patient's tcm syndrome total effectses relatively, sees Table 14.
Table 14 liang group patient tcm syndrome total effects relatively
| Group | The example number | Clinic control N (%) | Produce effects N (%) | Effective N (%) | Invalid N (%) | Control shows rate (%) | Total effective rate (%) |
| Treatment group matched group | 103 102 | 5(4.9) 2(2.0) | 29(28.2) 19(18.6) | 53(51.5) 56(54.9) | 16(15.5) 25(24.5) | 33.0 20.6 | 84.5 75.5 |
Ridit analyzes: treatment group and matched group compare: U=2.090 P＜0.05
Two groups of patient's tcm syndrome total effectses compare, and the treatment group is treated and is better than matched group, after the statistical procedures, and both difference significances.
4.5.8 every tcm symptom curative effect relatively sees Table 15 before and after two groups of patient treatments.
Every tcm symptom curative effect relatively before and after the table 15 liang group patient treatment
| Symptom | The treatment group | Matched group | Compare between group | |||||||||||
| The example number | Recovery from illness | Produce effects | Effectively | Invalid | Total effective rate | The example number | Recovery from illness | Produce effects | Effectively | Invalid | Total effective rate | U | P | |
| The dizziness and headache palpitation and insomnia | 100 92 78 72 | 46 54 45 37 | 4 1 1 0 | 35 16 19 12 | 15 21 13 23 | 85.0％ 77.2％ 83.3％ 68.1％ | 95 90 70 65 | 32 48 38 35 | 4 0 0 0 | 34 20 10 10 | 25 22 22 20 | 73.7％ 75.6％ 68.6％ 69.2％ | 2.000 0.590 0.975 0.230 | ＜0.05 ＞0.05 ＞0.05 ＞0.05 |
The tcm syndrome related symptoms all has improvement behind two groups of patient treatments, the treatment group all is better than matched group to curative effect dizzy, cardiopalmus, compares P＜0.05, difference significance between wherein dizzy group, compare P＞0.05, difference nonsignificance between all the other symptom curative effect groups.
4.5.9 two groups of patient's tcm syndrome integrations relatively, sees Table 16.
Table 16 liang group patient tcm syndrome integration relatively
| Group | The example number | X ± s before treating | Treat back x ± s | Difference x ± s | Self relatively | Compare between group | ||
| t | p | t | p | |||||
| Treatment group matched group | 103 102 | 10.796±2.857 10.372±2.630 | 4.651±2768 5.235±2.630 | 6.146±3.063 5.137±3.077 | 20.364 16.863 | 0.000 0.000 | 2.352 | 0.020 |
4.5.9.1 self compares before and after treatment group and the treatment of control group, the tcm syndrome integration significantly descends, P＜0.01, and difference has extremely significantly meaning.
4.5.9.2 the syndrome integration compares before and after treatment group and the treatment of control group, P＜0.05, and the difference significance, treatment group effect is better than matched group.
4.5.10 the picture of the tongue situation of change sees Table 17 before and after two groups of patient treatments.
Picture of the tongue situation of change before and after the table 17 liang group patient treatment
| Group | Add up to | Before the treatment | After the treatment | ||
| The assertive evidence picture of the tongue | Other | The assertive evidence picture of the tongue | Other | ||
| Treatment group matched group | 103 102 | 99 99 | 4 3 | 72 83 | 31 19 |
Picture of the tongue (red tongue) has better improvement before and after the treatment group patient treatment, and matched group changes little.
4.5.11 the pulse condition situation of change sees Table 18 before and after two groups of patient treatments.
Pulse condition situation of change before and after the table 18 liang group patient treatment
| Group | Add up to | Before the treatment | After the treatment | ||
| The assertive evidence pulse condition | Other | The assertive evidence pulse condition | Other | ||
| Treatment group matched group | 103 102 | 103 94 | 0 8 | 90 90 | 13 12 |
Pulse condition changes all little before and after two groups of patient treatments.
4.5.12 body weight change relatively sees Table 19 before and after two groups of patient treatments.
Body weight change compares (kg) before and after the table 19 liang group treatment
| Group | The example number | X ± s before treating | Treat back x ± s | Difference x ± s | Self relatively | Compare between group | ||
| t | P | t | P | |||||
| Treatment group matched group | 103 102 | 70.138±8.491 69.788±10.976 | 69.461±8.454 69.436±11.039 | 0.318±1.511 0.146±1.317 | 4.953 2.783 | 0.000 0.006 | 0.866 | 0.388 |
4.5.12.1 body weight change self relatively is P＜0.05, the difference significance before and after two groups of patient treatments.
4.5.12.2 compare P＞0.05, difference nonsignificance before and after two groups of patient treatments between the body weight set of variations.
4.5.13 the variation of blood pressure and heart rate before and after two groups of patient treatments
4.5.13.1 blood pressure relatively sees Table 20 before and after the group patient treatment.
The blood pressure curative effect compares (systolic pressure) (mmHg) before and after two groups of patient treatments of table 20-1
| Group | The example number | X ± s before treating | Treat back x ± s | Difference x ± s | Self relatively | Compare between group | ||
| t | P | t | P | |||||
| Treatment group matched group | 103 102 | 131.252±17.135 125.892±18.579 | 126.990±13.049 125.686±12.527 | 4.262±9.831 0.696±12.029 | 4.400 0.175 | 0.000 0.862 | 2.323 | 0.021 |
Systolic pressure self compares before and after (1) two group of patient treatment, treatment group P＜0.01, and difference has extremely significantly meaning; Matched group P＞0.05, the difference nonsignificance.
Compare P＞0.05, difference nonsignificance between the group of (2) two groups of patient treatment front and back systolic pressure variations.
The blood pressure curative effect compares (diastolic pressure) (mmHg) before and after two groups of patient treatments of table 20-2
| Group | The example number | X ± s before treating | Treat back x ± s | Difference x ± s | Self relatively | Compare between group | ||
| t | P | t | P | |||||
| Treatment group matched group | 103 102 | 82.544±9.448 79.363±9.262 | 79.544±7.388 79.480±8.184 | 3.000±7.855 -0.118±5.877 | 3.876 -0.202 | 0.000 0.840 | 3.220 | 0.002 |
Diastolic pressure self compares before and after (1) two group of patient treatment, treatment group P＜0.01, and difference has extremely significantly meaning; Matched group P＞0.05, the difference nonsignificance.
Compare P＜0.05, difference significance before and after (2) two groups of patient treatments between the diastolic pressure group.
4.5.13.2 heart rate relatively sees Table 21 before and after two groups of patient treatments.
Heart rate relatively before and after the table 21 liang group patient treatment
| Group | The example number | X ± s before treating | Treat back x ± s | Difference x ± s | Self relatively | Compare between group | ||
| t | P | t | P | |||||
| Treatment group matched group | 103 102 | 77.728±8.384 75.980±8.965 | 76.767±8.651 75.039±7.864 | 0.961±6.052 0.941±6.465 | 1.612 1.470 | 0.110 0.145 | 0.023 | 0.982 |
Heart rate self relatively is P＞0.05, the difference nonsignificance before and after (1) two group of patient treatment.
Compare P＞0.05, difference nonsignificance before and after (2) two groups of patient treatments between the heart rate group.
4.5.14 the relation of the treatment group course of disease and blood fat curative effect sees Table 22.
The relation of the table 22 treatment group course of disease and blood fat curative effect
| The course of disease (year) | The example number | Clinic control N | Produce effects N | Effective N | Invalid N | Control shows rate % | Total effective rate % |
| ＜1 1～ 5～ 10～ | 14 69 13 7 | 1 9 2 0 | 4 19 3 3 | 5 28 4 3 | 4 13 4 1 | 35.7 40.6 38.5 42.9 | 71.4 81.2 69.2 85.7 |
Multi-group data Ridit analyzes: X
2=0.83 P＞0.05
It is close that different course of disease patient's blood fat curative effects are organized in treatment, P＞0.05, difference nonsignificance.
4.5.15 the relation of treatment group age and blood fat curative effect sees Table 23.
The relation of table 23 treatment group age and blood fat curative effect
| Age (year) | The example number | Clinic control N | Produce effects N | Effective N | Invalid N | Control shows rate % | Total effective rate % |
| 18～ 31～ 41～ 51～65 | 3 13 33 54 | 0 0 3 9 | 1 6 12 11 | 1 4 13 21 | 1 3 5 13 | 33.3 46.2 45.5 37.0 | 66.7 76.9 84.8 75.9 |
Multi-group data Ridit analyzes: X
2=0.60 P＞0.05
Treatment group each age group blood fat curative effect is close, P＞0.05, difference nonsignificance.
4.5.16 the relation of treatment group sex and blood fat curative effect sees Table 24.
The relation of table 24 treatment group sex and blood fat curative effect
| Sex | The example number | Clinic control N | Produce effects N | Effective N | Invalid N | Control shows rate % | Total effective rate % |
| Masculinity femininity | 56 47 | 6 6 | 19 11 | 17 22 | 14 8 | 44.6 36.2 | 75.0 83.0 |
Ridit analyzes: U=0.01 P＞0.05
The blood fat curative effect compares between treatment group men and women, P＞0.05, difference nonsignificance.
4.5.17 the relation of the treatment group traditional Chinese medical science state of an illness and blood fat curative effect sees Table 25.
The relation of the table 25 treatment group traditional Chinese medical science state of an illness and blood fat curative effect
| The state of an illness | The example number | Clinic control N | Produce effects N | Effective N | Invalid N | Control shows rate % | Total effective rate % |
| Slight moderate severe | 19 71 13 | 2 8 2 | 3 21 6 | 9 28 2 | 5 14 3 | 26.3 40.8 61.5 | 73.7 80.3 76.9 |
Multi-group data Ridit analyzes: X
2=1.811 P＞0.05
It is close that different state of an illness person's blood fat curative effects are organized in treatment, P＞0.05, difference nonsignificance.
4.5.18 two groups of patient's trial drugs are taken situation, see Table 26.
Table 26 a liang group patient trial drug is taken situation
| Group | The example number | All take N (%) | Sometimes miss N (%) | 1/3 does not obey N (%) | The long-term N (%) that interrupts |
| Treatment group matched group | 103 102 | 103(100.0) 102(100.O) | 0 0 | 0 0 | 0 0 |
Two groups of patient's compliances are good.
4.6 safety detects
To treatment group and matched group patient, carry out routine blood test, routine urinalysis, just routine, liver function, renal function, Electrocardioscopy respectively before and after the treatment in the clinical trial, seen table 27 for details.
Table 27 security inspection
| Project | Group | Before the treatment | After the treatment | ||||
| The test example number | Normally | Unusually | The test example number | Normally | Unusually | ||
| The routine blood test routine urinalysis is conventional GPT Cr BUN electrocardiogram just | Treatment group treatment of control group group treatment of control group group treatment of control group group treatment of control group group treatment of control group group treatment of control group group control group | 103 102 103 102 103 102 101 102 101 102 101 102 103 102 | 103 98 98 91 103 102 94 94 98 100 100 99 84 80 | 0 4 5 11 0 0 7 8 3 2 1 3 19 22 | 103 102 103 102 103 102 103 102 103 102 103 102 103 102 | 103 99 99 97 103 102 99 95 101 101 102 99 85 82 | 0 3 4 5 0 0 4 7 2 1 1 3 18 20 |
Remarks:
Routine blood test: matched group is treated preceding 4 routine anemias, and treat back 1 example and transfer to normally, 3 routine no changes, normal 1 example is also irrelevant with the matched group medication.
Routine urinalysis: the treatment group has 5 routine patients unusual before treating, and 3 examples are slight urinary tract infection for microalbumin .2 example is arranged in the urine, all have 1 example to recover normal after the latter treats, and all the other no changes are considered with medication irrelevant.
Matched group 11 examples are unusual, have 4 examples to be slight urinary tract infection, treat back 2 examples and recover normal, 2 routine no changes; In the 7 example urine is microalbumin, and the urine protein for the treatment of back 4 examples disappears, and 3 routine no changes are considered also irrelevant with medication.
Just conventional: all normal after treating before treatment group and matched group are treated.
Liver function: the treatment group is treated preceding 7 routine GPT and is slightly raise, and treats back 3 examples and recovers normal, and 4 routine no changes are thought of as due to the slight fatty liver, treat back rate and blood-lipid decreased burden of liver and alleviate, and liver function takes a turn for the better, also may be irrelevant with the test medication.
Matched group is treated preceding 8 routine GPT and is slightly raise, and treats back 1 example and recovers normal, 7 routine no changes.
Renal function: the treatment group has 3 routine Cr slightly to raise before treating, and it is normal to treat back 1 example, and 2 routine no change: BUN treat preceding 1 example and raise, and treat the back no change.
Matched group is treated preceding 2 routine patient Cr and is slightly raise, and it is normal to treat back 1 example, 1 routine no change; BUN treats preceding 3 examples and raises, and treats the back no change.
Electrocardiogram: the treatment group is treated preceding 18 examples has myocardial ischemia ST-T to change, and treat back 1 example and recover normal, 17 routine no changes, 1 example is right bundle branch block fully, and it is constant to treat the back.
Matched group is treated preceding 22 examples has ischemic ST-T to change, and treats back 2 examples and recovers normal, 20 routine no changes.Two groups of patients all do not find newly-increased unusual case.
4.7 analysis of adverse reactions
The treatment group laxativeness occurs after 1 routine patient's medication is arranged, and not special handling disappeared after 2-3 days, adheres to that medication does not occur again; Other has 1 routine patient to take medicine ante cibum the gastral cavilty distension to occur, occurs after changing one after each meal into again.
4.8 conclusion
SONGLING XUEMAIKANG has definite blood fat reducing curative effect, and Primary hyperlipemia excessive rising of liver-YANG person is had therapeutical effect preferably, has no adverse reaction and toxic and side effects, and is safe and convenient to use.
5 drying process with atomizing Study on Conditions
5.1 the extractum relative density is investigated
The technology that present Chinese patent medicine is made dry extract often adopts spray drying, and the relative density of clear paste generally is controlled at 1.15-1.30 (and former patent is to be controlled at 1.08) 70 ℃ of detections in the production reality.Because after Chinese medical concrete was concentrated into certain relative density, the solution thickness if relative density is excessive, then can influence spray-dired effect, so the relative density of clear paste is investigated.Get each four parts of extracting solution, concentrating under reduced pressure is 1.18,1.20,1.22 to relative density, 1.24 according to the existing equipment performance, setting the tower pathogenic wind-warm is 220 ℃, go out the tower pathogenic wind-warm and be 100-110 ℃ to carry out spray drying, observe: be concentrated to after relative density is 1.20, spray pattern was good when clear paste carried out spray drying, be beneficial to spray drying, the dry extract granule is moderate: too thick blocking sprayer of other conditions or dried granules are very thin, lose very greatly, production efficiency is low, so optimum condition is 1.20 (70 ℃) for selecting clear paste to be concentrated to relative density.
5.2 spray drying is advanced the investigation of tower pathogenic wind-warm: for effectively clear paste being carried out spray drying, according to practical experience and existing equipment performance, setting the tower pathogenic wind-warm is 230 ℃, 220 ℃, 210 ℃, going out the tower pathogenic wind-warm and be 100-110 ℃ advances the tower pathogenic wind-warm and investigates, result's dry extract when advancing the tower pathogenic wind-warm and be 230 ℃ is prone to the gelatinizing phenomenon, and sticking tower is comparatively serious, and color is dark, and empyreumatic taste is arranged, tower pathogenic wind-warm height has been described into; 210 ℃ sticking tower phenomenon all occurs, and dry extract is easily collecting not, illustrates that into the tower pathogenic wind-warm is low; 220 ℃ sticking tower, gelatinizing, empyreuma phenomenon occur, and the dry extract granule is moderate collects, so adopt 220 ℃ the tower pathogenic wind-warm of advancing to be the best.
5.3 spray drying goes out the investigation of tower pathogenic wind-warm: advancing the tower pathogenic wind-warm is 220 ℃, go out the tower pathogenic wind-warm and under 90-100 ℃, 100-110 ℃, 110-120 ℃ condition, carry out spray drying experiment, under 90-100 ℃ of condition, dry extract moisture content exceeds standard (5%), under 110-120 ℃ of condition, dry extract gelatinizing and sticking tower, empyreumatic taste is yellow at 100-110 ℃ of dry extract easily collecting, and moisture is 1.7%, no gelatinizing, sticking tower, empyreumatic taste are controlled at 100-110 ℃ for best so go out the tower pathogenic wind-warm.
5.4 conclusion
Preferred spray drying condition, adopting relative density is 1.20 (70 ℃) clear paste liquid, advancing the tower pathogenic wind-warm is 220 ℃, goes out 100-110 ℃ of technology of tower pathogenic wind-warm and carries out spray drying.
6. soft capsule preparation technical study
6.1 substrate is selected
It is disperse matrix that soft capsule is generally selected vegetable oil, comprise soybean oil, Oleum Arachidis hypogaeae semen, vegetable oil etc., the water solublity Chinese medical concrete also can be selected water-soluble base PEG400 etc., selects for use PEG400 need be suspended in the substrate for the substrate content can not dissolve fully by a large amount of evidences, poor stability; Adopt vegetable oil as substrate, stability is also not so good, selects soybean oil and Oleum Arachidis hypogaeae semen content good stability for use.
6.2 wetting agent is selected
The water solublity Chinese medicine powder generally need in the oleaginous base prescription to select surfactants such as adding wetting agent such as polysorbate60, Tween 80, lecithin, by experimental results demonstrate that this product need not add wetting agent and just can guarantee the stable of product.
6.3 the selection of suspending agent
The soft capsule suspending agent is generally selected the macromolecule oil-soluble material to be dissolved in and is guaranteed the stable of content in the oleaginous base, prove that by experiment Cera Flava, monostearate, paraffin oil, aluminum monostearate or ethyl cellulose all can be used as the suspensoid of this product, but preferred Cera Flava and aluminum monostearate, the best is a Cera Flava.
64 content prescription screenings
In order to guarantee to be pressed into qualified soft capsule, when the fill soft capsule, be easy to fill, guarantee that the soft capsule quality of fill is stable, content has been carried out prescription screening.
Experimental technique: take by weighing 9 parts in medicated powder, every part 100 gram places beaker.Wherein three parts add soybean oil 90 grams, 100 grams, 110 grams that contain Cera Flava 1% respectively, wherein three parts add soybean oil 90 grams, 100 grams, 110 grams that contain Cera Flava 2% respectively, wherein three parts add soybean oil 90 grams, 100 grams, 110 grams that contain Cera Flava 3% respectively, and with stability, flowability is that index is investigated, and the results are shown in following table.From table as can be known: No. 1-No. 3 good fluidity, but stability remove No. 1 relatively poor, other inequality are so can not select; No. 7-No. 9 stability is all better, but flowability is all relatively poor, so can not select; No. 4-No. 6 flowability is all better, stability might as well, so all optional, promptly supplementary product consumption is that positive and negative 10% of extract powder consumption gets final product with interior.
The screening of content prescription
7 gelatin solution prescription screenings
The capsule material of soft capsule generally is made up of gelatin, G ﹠ W.Usually suitable weight ratio is a gelatin: glycerol: water is 10: 4～6: 8～12; , and be 1: 1 between water and the dry gelatin.
Draft several prescriptions and compare, determine the best prescription of glue, see the following form.
The gelatin solution prescription screening
| Numbering | Gelatin | Glycerol | Water |
| 1 | 50g | 20g | 40g |
| 2 | 50g | 25g | 50g |
| 3 | 50g | 30g | 60g |
| 4 | 50g | 20g | 50g |
| 5 | 50g | 30 | 60 |
| 6 | 50g | 25 | 40 |
| 7 | 50g | 25 | 60 |
| 8 | 50g | 30 | 40 |
| 9 | 50g | 20 | 50 |
Prescription screening index: the hardness of A soft capsule; The disintegration of B soft capsule;
7.1 the compound method of glue: after the gelatin that takes by weighing recipe quantity is put and made its abundant swelling in the purified water, add glycerol and other adjuvant, add water to full dose, heating, 55 ℃ of insulations, evacuation stirs, and it is standby to survey moisture qualified back insulation.
7.2 preparation of soft capsule: machine revolving die compacting soft capsule on the medicinal liquid that makes by the medicinal liquid preparing process and the 55 ℃ of gelatin solutions, in rotating cage with after the solidifying by cooling in wind molding, with ethanol flush away surface oil reservoir, in 20～30 ℃ of hot blasts in dry, promptly.
7.3 the mensuration of disintegration: by " an appendix XD of Chinese pharmacopoeia page or leaf is measured, and is medium with 37 ℃ of water, is being added with under the plate washer condition, checks the disintegration of soft capsule.
7.4 result
Be gelatin 7.4.1 optimize prescription: glycerol: water is 1: 0.4～0.6: 1
74.2 the gelatin solution best prescription is:
Gelatin: 50Kg glycerol: 20Kg purified water: 50Kg
8, the external stripping experiment of this prescription soft capsule and hard capsule relatively
Method is: prepare a collection of soft capsule and a collection of hard capsule by this patent method, carry out the dissolution experiment by the dissolution method of Chinese Pharmacopoeia 2000 editions, detecting index is the effective ingredient puerarin, and content assaying method is a high performance liquid chromatography, and the result is as follows:
| Minute | 5 | 10 | 15 | 20 | 30 | 45 | 60 |
| Soft capsule | 3％ | 10％ | 20％ | 85％ | 95％ | 98％ | 96％ |
| Hard capsule | 5％ | 13％ | 35％ | 45％ | 60％ | 80％ | 92％ |
From above experiment as can be seen, preceding 15 minutes of capsule disintegrate, both dissolution rate basically identicals, even hard capsule is also fast than soft capsule, but after the whole disintegrates of capsule in 20 minutes, soft capsule goes out medicine with regard to abrupt release, and hard capsule demonstrates the trend of slow stripping at once, pass through to granulate with hard capsule medicated powder obviously, the effective ingredient stripping is relevant slowly.
9, embodiment
Embodiment 1
The crude drug weight proportion is:
Bright Folium Pini 3600g Radix Puerariae 600g Margarita layer powder 90g
Get bright Folium Pini, the Radix Puerariae medical material of above-mentioned consumption proportion, decoct with water twice, add 8 times of water gagings for the first time, decocted 1.5 hours, the water that adds for the second time 6 times of amounts, decocted 1.5 hours, collecting decoction filters, and filtrate decompression is condensed into that relative density detects 70 ℃ the time is 1.2 extractum, get extractum liquid carry out spray drying (advance 220 ℃ of tower pathogenic wind-warm, go out 110 ℃ of tower pathogenic wind-warm) dry extract, standby; Get Cera Flava 10g thermosol in the soybean oil of 365g, slowly drop into dry extract and Margarita layer powder, fully be processed into medicinal liquid with colloid mill behind the mix homogeneously; In gelatin: glycerol: water is that 5: 2: 5 ratio prepares gelatin solution; With medicinal liquid and gelatin solution, be pressed into the soft capsule of predetermined weight by pellet press, through the drying of finalizing the design, wash ball, select ball, packing promptly.
Embodiment 2
The crude drug weight proportion is:
Bright Folium Pini 3000g Radix Puerariae 600g Margarita layer powder 90g
Get bright Folium Pini, the Radix Puerariae medical material of above-mentioned consumption proportion, decoct with water twice, add 7 times of water gagings for the first time, decocted 1 hour, the water that adds for the second time 5 times of amounts, decocted 1 hour, collecting decoction filters, and filtrate decompression is condensed into that relative density detects 70 ℃ the time is 1.2 extractum, get extractum liquid carry out spray drying (advance 220 ℃ of tower pathogenic wind-warm, go out 100 ℃ of tower pathogenic wind-warm) dry extract, standby; Get aluminum monostearate 9g thermosol in the soybean oil of 350g, slowly drop into dry extract and Margarita layer powder, fully be processed into medicinal liquid with colloid mill behind the mix homogeneously; In gelatin: glycerol: water is that 5: 2: 5 ratio prepares gelatin solution; With medicinal liquid and gelatin solution, be pressed into the soft capsule of predetermined weight by pellet press, through the drying of finalizing the design, wash ball, select ball, packing promptly.
Embodiment 3
The crude drug weight proportion is:
Bright Folium Pini 5000g Radix Puerariae 600g Margarita layer powder 90g
Get bright Folium Pini, the Radix Puerariae medical material of above-mentioned consumption proportion, decoct with water twice, add 9 times of water gagings for the first time, decocted 2 hours, the water that adds for the second time 8 times of amounts, decocted 2 hours, collecting decoction filters, and filtrate decompression is condensed into that relative density detects 70 ℃ the time is 1.2 extractum, get extractum liquid carry out spray drying (advance 220 ℃ of tower pathogenic wind-warm, go out 110 ℃ of tower pathogenic wind-warm) dry extract, standby; Get Cera Flava 15g thermosol in the soybean oil of 415g, slowly drop into dry extract and Margarita layer powder, fully be processed into medicinal liquid with colloid mill behind the mix homogeneously; In gelatin: glycerol: water is that 5: 2: 5 ratio prepares gelatin solution; With medicinal liquid and gelatin solution, be pressed into the soft capsule of predetermined weight by pellet press, through the drying of finalizing the design, wash ball, select ball, packing promptly.
Embodiment 4
The crude drug weight proportion is:
Bright Folium Pini 3600g Radix Puerariae 600g Margarita layer powder 90g
Get bright Folium Pini, the Radix Puerariae medical material of above-mentioned consumption proportion, decoct with water twice, add 8 times of water gagings for the first time, decocted 1.5 hours, the water that adds for the second time 6 times of amounts, decocted 1.5 hours, collecting decoction filters, and filtrate decompression is condensed into that relative density detects 70 ℃ the time is 1.2 extractum, get extractum liquid carry out spray drying (advance 220 ℃ of tower pathogenic wind-warm, go out 105 ℃ of tower pathogenic wind-warm) dry extract, standby; Get Cera Flava 10.2g thermosol in the Oleum Arachidis hypogaeae semen of 389.8g, slowly drop into dry extract and Margarita layer powder, fully be processed into medicinal liquid with colloid mill behind the mix homogeneously; In gelatin: glycerol: water is that 5: 2: 5 ratio prepares gelatin solution; With medicinal liquid and gelatin solution, be pressed into the soft capsule of predetermined weight by pellet press, through the drying of finalizing the design, wash ball, select ball, packing promptly.
Claims (17)
1. a Chinese medicine for the treatment of hypertension and hyperlipidemia is characterized in that it is the medicament of being made by the crude drug of following weight
Bright Folium Pini 3000～5000g Radix Puerariae 400～800g
Margarita layer powder 50～120g.
2. the Chinese medicine of treatment hypertension according to claim 1 and hyperlipidemia is characterized in that the weight of each crude drug is
Bright Folium Pini 3000g～4000g Radix Puerariae 500～700g
Margarita layer powder 80～100g.
3. the Chinese medicine of treatment hypertension according to claim 1 and hyperlipidemia is characterized in that the weight of each crude drug is
Bright Folium Pini 3600g Radix Puerariae 600g Margarita layer powder 90g.
4, according to claim 1 to 3 each described treatment hypertension and hyperlipidemia Chinese medicine, the dosage form that it is characterized in that this Chinese medicine is a soft capsule.
5. the preparation method of Chinese medicine of described treatment hypertension of claim 4 and hyperlipidemia is characterized in that it is to take following steps to make:
Step 1: extract: bright Folium Pini, the Radix Puerariae medical material of getting formula ratio, decoct with water twice, add for the first time 6～9 times of water gagings, decocted 1～2 hour, and added the water of 5～8 times of amounts for the second time, decocted 1～2 hour, collecting decoction, filter, and filtrate decompression is condensed into that relative density detects 70 ℃ the time is 1.1～1.3 extractum, gets extractum liquid and carry out spray drying and get dry extract;
Step 2: the preparation gelatin solution: the ratio of gelatin, glycerol, water is 10: 4～6: 8～12;
Step 3; The preparation of medicinal liquid: get the suspending agent thermosol in substrate, slowly drop into step 1 gained dry extract and Margarita layer powder, fully handle with colloid mill behind the mix homogeneously;
Step 4: pill: with medicinal liquid and gelatin solution, be pressed into the soft capsule of predetermined weight, through the drying of finalizing the design, wash ball, packing promptly by pellet press.
6. treatment hypertension according to claim 5 and hyperlipidemia preparation method of Chinese medicine is characterized in that decocting with water twice in the step 1, add 8 times of water gagings for the first time, decoct 1.5 hours, add the water of 6 times of amounts for the second time, decoct 1.5 hours.
7. treatment hypertension according to claim 5 and hyperlipidemia preparation method of Chinese medicine is characterized in that filtrate decompression in the step 1 is condensed into that relative density detects in the time of 70 ℃ be 1.2 extractum.
8. treatment hypertension according to claim 5 and hyperlipidemia preparation method of Chinese medicine is characterized in that the spray drying condition is in the step 1: advance 220 ℃ of tower pathogenic wind-warm, go out 100-110 ℃ of tower pathogenic wind-warm.
9. treatment hypertension according to claim 5 and hyperlipidemia preparation method of Chinese medicine is characterized in that the ratio of gelatin in the step 2, glycerol, water is: 5: 2: 5.
10. treatment hypertension according to claim 5 and hyperlipidemia preparation method of Chinese medicine is characterized in that the suspending agent in the step 3 is Cera Flava, monostearate, paraffin oil, aluminum monostearate or ethyl cellulose.
11. treatment hypertension according to claim 5 and hyperlipidemia preparation method of Chinese medicine is characterized in that the suspending agent in the step 3 is Cera Flava or aluminum monostearate.
12. treatment hypertension according to claim 5 and hyperlipidemia preparation method of Chinese medicine is characterized in that the suspending agent in the step 3 is Cera Flava 2～20g.
13. treatment hypertension according to claim 5 and hyperlipidemia preparation method of Chinese medicine is characterized in that the suspending agent in the step 3 is Cera Flava 5～15g.
14. treatment hypertension according to claim 5 and hyperlipidemia preparation method of Chinese medicine is characterized in that the substrate in the step 3 is soybean oil, Oleum Arachidis hypogaeae semen, vegetable oil or PEG400.
15. treatment hypertension according to claim 5 and hyperlipidemia preparation method of Chinese medicine is characterized in that the substrate in the step 3 is soybean oil or Oleum Arachidis hypogaeae semen.
16. treatment hypertension according to claim 5 and hyperlipidemia preparation method of Chinese medicine is characterized in that the substrate in the step 3 is soybean oil 200～800g.
17. treatment hypertension according to claim 5 and hyperlipidemia preparation method of Chinese medicine is characterized in that the substrate in the step 3 is soybean oil 300～600g.
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| CN103123343B (en) * | 2012-07-13 | 2014-05-14 | 成都康弘制药有限公司 | Quality control method for Songling Xuemaikang capsules |
| CN103238774A (en) * | 2013-04-28 | 2013-08-14 | 洪圣娟 | Coix seed puerarin pine leaf soup |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1039784C (en) * | 1995-07-27 | 1998-09-16 | 吉玲 | Traditional Chinese proprietary medicine for curing hypertension |
| CN1565564A (en) * | 2003-06-26 | 2005-01-19 | 湖南长沙天人医药技术开发有限公司 | Preparation method of |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1039784C (en) * | 1995-07-27 | 1998-09-16 | 吉玲 | Traditional Chinese proprietary medicine for curing hypertension |
| CN1565564A (en) * | 2003-06-26 | 2005-01-19 | 湖南长沙天人医药技术开发有限公司 | Preparation method of |
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