CN1112196C - Medicine for regulating blood fat and reducing plasma fibrin - Google Patents

Abstract

The present invention relates to medicine for adjusting blood fat and reducing blood plasma fibre protein. The components of the present invention are prepared from 85 to 95% of alisma, 4 to 14% of myrrh and chitosan as the rest. The present invention has the preparation technology that the alisma and the myrrh are dried and are coarsely crushed. Coarse powder are immersed by 90% of ethanol as washing liquid for one night. The coarse powder is leached in a dynamic state, and residues are removed. The ethanol is filtrated and recovered by an extracting solution, and then the ethanol is concentrated into a thick paste shape. After chitosan is added in the thick paste and is evenly mixed, obtained thick paste is dried below 70 DEG C. The obtained thick paste is crushed into fine powder of 100 meshes and is encapsulated to obtain a finished product. The new medicine has the advantages of outstanding curative effect and no side effect and can be used as medicine for lowering blood fat and blood plasma fibre protein.

Description

A kind of medicine that has blood lipid regulation and reduce plasma fibrin

The present invention relates to a kind of medicine that has blood lipid regulation and reduce plasma fibrinogen.

As everyone knows, hyperlipemia is to cause one of topmost risk factors of cardiovascular and cerebrovascular disease such as coronary heart disease.Over past ten years, people have had further understanding to the paathogenic factor of cardiovascular and cerebrovascular vessel embolism class diseases, think that plasma fibrinogen is higher than its hazardness that is brought of normal population and raises far above blood fat.Clinical research confirmation is arranged, and the incidence rate of elderly population myocardial infarction in winter and cerebral infarction and mortality rate all are higher than summer.Reason be winter the human plasma Fibrinogen all rise 23%.As with plasma fibrinogen among the crowd and cholesterol level by high, medium and low grouping (high group: be higher than standard deviation of average; Low group: be lower than standard deviation of average), then their incidence rate of myocardial infarction increases by 84% in high plasma fibrinogen group, and the hypercholesterolemia group increases by 43%.Therefore, when actively blood fat reducing is treated, also must reduce plasma fibrinogen, this is even more important to preventing and treating the cardiovascular and cerebrovascular vessel embolism class diseases.At present, it is also rare to have blood lipid regulation and reduce the effective medicine of plasma fibrinogen, owing to existing multiple side effect to limit use.

The blood fat reducing that the object of the present invention is to provide a kind of determined curative effect and have no side effect can reduce the medicine of plasma fibrin simultaneously.

Task of the present invention realizes as follows: get Rhizoma Alismatis 85-95%, Myrrha (processed) 4-14%, surplus is a chitosan.

Its production technology is:

A, get Rhizoma Alismatis, system is soaked medicine, drying, coarse crushing;

B, get coarse powder, soak into 90% ethanol washing liquid, spend the night, dynamically lixiviate discards residue;

C, extracting solution are crossed rate and are reclaimed ethanol, are concentrated into the thick paste shape, and after the adding chitosan was mixed, oven dry was pulverized 100 order fine powders and incapsulated below 70 ℃.

Medicine of the present invention is that the alcohol extraction position with the natural plant decoction pieces is active ingredient, so good effect, is free from side effects.

A most preferred embodiment of the present invention is got Rhizoma Alismatis 85kg, Myrrha 14kg decoction pieces component, and coarse crushing is spent the night with 90% soak with ethanol, and dynamically lixiviate is 1 hour, filter, and decompression filtrate recycling ethanol, and be concentrated into thick paste; The chitosan that the adds 0.1kg back oven dry below 70 ℃ that is mixed is pulverized, 100 order fine powders encapsulated 2800 promptly.

Second most preferred embodiment of the present invention got Rhizoma Alismatis 9.5kg, Myrrha 0.4kg decoction pieces component, and coarse crushing is spent the night with 90% soak with ethanol, and dynamically lixiviate is 1 hour, filter, and decompression filtrate recycling ethanol, and be concentrated into thick paste; The chitosan that the adds 0.1kg back oven dry below 70 ℃ that is mixed is pulverized, and 100 order fine powders are encapsulated, promptly.

The mechanism of curing the disease of the present invention is:

The glutinous rate of hyperlipemia and blood increases, and belongs to motherland's medical science phlegm-damp stasis of blood resistance category.Its clinical symptoms generally has: spiritlessness and weakness, pareordia twinge, or dizziness uncomfortable in chest or the fat body heap soil or fertilizer over and around the roots of shape, heaviness sensation over the head and body etc.Its etiology and pathogenesis research is thought: the generation of its cause of disease and liver,spleen,kidney three dirty relations are the closest.Because surfeit highgrain savoury or be addicted to drink immoderately, liver, taste are impaired, strong fortune lose can, give birth in the phlegm-damp; Old asthenia, the hepatic and renal YIN deficiency, excessive rising of liver-YANG, the prosperous gram soil of wood, taste intrinsic heat, then expectorant Re Neisheng; Accumulate in turbid by expectorant and then blood stasis resistance network influence mechanism of qi and then is disease.The get to the bottom of sb.'s illness importance of pathogenesis is existing turbid damp, blood stasis is arranged again, and influence each other.So clinical treatment is when being to remove turbid damp, promoting blood circulation is with clear its root.Medicinal Rhizoma Alismatis, sweet expectorant eliminating dampness by diuresis, diuretic and the product of non-impairment of YIN, the logical internal organs of a surname are wet, remove dirty material in the body.Modern medicine study shows that American waerplantain triterpenoidal class alcohol extract can suppress 3-hydroxyl-3-first glutaryl coenzyme A (HMG-CoA) reductase activity, and the pharmacological action and the lipotropy of treatment zoopery hyperlipemia arranged.Myrrha, its flat dissipating blood stasis is logical to stagnate, and invigorates blood circulation to win and wets, and helps the removing of dirty material in the body.Modern medicine study shows the class alcohol extract, and myrrh lipid alcohol extract has the inhibition cholesterol absorption, and can obviously reduce plasma fibrinogen level, and secondary increased fibrinolytic activity due to the hypercoagulability is had therapeutical effect.In sum, two medicines are auxilliary mutually in the side is usefulness, focuses on dampness removing and helps blood circulation promoting and blood stasis dispelling, invigorating blood circulation looses stagnate and benefit dampness removing cut turbid, to reach turbid wet going, the purpose that blood vessels are logical.Cure mainly feeling of oppression and pain in the chest, diseases such as dizziness due to fluid-retention.Be applicable to diseases such as coronary heart disease hyperlipemia, diabetes, hypertension.

An important feature of medicine of the present invention is, it is to integrate modern molecule Chinese medicine and pharmacy that this medicine is formed---molecular network is regulated theoretical and traditional traditional Chinese medical science treatment based on differentiation of disease, it is clear to have the mechanism of action, and active ingredient is clear and definite, adopts modern pharmaceutical technology and adjuvant to be processed into.Another important feature of medicine of the present invention is, employed novel adjuvant chitosan in the medicament prescription, it can prevent composition such as poponax resin to the gastrointestinal stimulation, and can improve the curative effect of medicine and make the preparation design of medicine of the present invention more scientific and reasonable.

Medicine of the present invention has the cholesterol reducing amplitude, improve former low-level blood middle-high density lipoprotein and cholesterol and with the ratio of triglyceride, and the pharmacological action that reduces plasma fibrinogen is simultaneously arranged, cardiovascular diseases such as coronary heart disease are prevented and treated curative effect.

The ZWW clinical trial protocol:

One, test objective

By clinical trial, evaluation is made in the curative effect and the safety of " ZWW " treatment hyperlipemia.

Two, diagnostic criteria

(1) tcm diagnosis standard

The traditional Chinese medical science is divided into three types with hyperlipemia, wherein accounts for first place (sickness rate is the highest) with the hepatic and renal YIN deficiency.According to the composition and the function of " ZWW ", cure mainly the hepatic and renal YIN deficiency, give birth in the damp-phlegm of holding concurrently and qi depression to blood stasis and cause disease such as waist soreness.

Hepatic and renal YIN deficiency disease: waist soreness, vertigo and tinnitus, seminal emission night sweat, dry mouth and throat, dysphoria with feverish sensation in the chest palms and soles, red tongue with a little fluid, thready pulse speed.

More than all symptom for the essential condition of diagnosis (except that pass out semen, the thready pulse speed).

The disease of holding concurrently lifes in the damp-phlegm: headache as wrap up in, the tired power of body, enlarged tongue bitterly are bored with, the stringy pulse slip velocity.

The disease of the qi depression to blood stasis of holding concurrently: uncomfortable in chestly do not relax, the vexed pain in front, twinge are handed over and done, the body of the tongue tong-test ammeter has ecchymosis, deep and hesitant pulse or knot generation.

(2) Western medicine diagnose standard

Through domestic investigation of several years, research also proposes the unified diagnostic criteria in the whole nation with reference to foreign data according to the biochemistry expert Li Jianzhai researcher of Beijing Gerontological Research Center institute, and its condition is as follows:

Hypercholesterolemia: TC＞6.5mmol/L (250mg%); Hypertriglyceridemia: TG＞2.2mmol/L (200mg%); The boundary of low density lipoprotein, LDL (LDL-C) is 4.16mmol/L (160mg); High density lipoprotein (HDL-C) is no less than 0.91mmol/L (35mg%).

Three, case inclusion criteria

All Western medicine diagnose hyperlipemias and the also dialectical genus hepatic and renal YIN deficiency of the traditional Chinese medical science also have disease cases such as waist soreness and all can include the observation case in.

Four, case exclusion standard

Following disease is classified the eliminating case as: 1, familial hereditary hypercholesterolemia; 2, the nephrotic syndrome; 3, renal transplant patient; 4, chronic uremia patient; 5, acute and chronic hepatitis patient; 6, diabetes patient; 7, do not meet tcm diagnosis and debate disease standard and condition, as excessive rising of liver-YANG, stomach yang deficiency etc.; 8, the age was greater than 70 years old; 9, use other blood lipid-lowering medicines person drug withdrawal to be less than 1 month.

Five, test method

Take random packet parallel check experiment method.

(1) random method and step: by the first group: second group=3: 1, but then regulation to meet the random digit last digit be 1,2,3,5,6,7 to divide to the first group, 4,8 divide to the second group; Mantissa 0,9 discards (new Chinese medicine development with declare nineteen ninety-five 299 pages of versions).The first group is test group 300 examples, and the second group is matched group 100 examples.Each is organized experimenter's numbering and sees Table 1.

This test adopts single blind method to observe.

(2) Therapeutic Method

1, test group: give " ZWW ", provide by pharmacology teaching and research room of Harbin Medical University.

1., small dose group: 2/time, 3 times/day;

2., heavy dose of group: 3/time, 3 times/day.

2, matched group: give the vitamin nicotinate capsule, provide by the Harbin No.6 Pharmaceutical Factory, 2/time, 3 times/day.

Be 30 days two groups of courses of treatment.

(3) observation item and method

1, clinical symptoms and sign: waist soreness, vertigo and tinnitus, seminal emission night sweat, dry mouth and throat, dysphoria with feverish sensation in the chest palms and soles, red tongue with a little fluid, thready pulse speed, the disease (seeing diagnostic criteria) of holding concurrently; Untoward reaction (seeing the observation table).

2, lab testing project: blood, urine, just conventional; T-CHOL, triglyceride, low density lipoprotein, LDL, high density lipoprotein; GPT, GOT, BUN.

Six, disease appraisal standards

According to the symptom and the performance of double disease of the hepatic and renal YIN deficiency, mainly examine or check the following, and carry out the sxemiquantitative examination by scoring method.

(1) waist soreness

There is not 0 fen

Initiatively said 4 fens

Get, significantly or continue to occur 3 fens

It is heavy or be interrupted to occur 2 fens when time thes be light

Gently or once in a while occur 1 fen

(2) vertigo and tinnitus

There is not 0 fen

Initiatively said 4 fens

Get, significantly or continue to occur 3 fens

It is heavy or be interrupted to occur 2 fens when time thes be light

Gently or once in a while occur 1 fen

(3) seminal emission

There is not 0 fen

Initiatively said 4 fens

Get, significantly or continue to occur 3 fens

It is heavy or be interrupted to occur 2 fens when time thes be light

Gently or once in a while occur 1 fen

(4) night sweat

There is not 0 fen

Initiatively said 4 fens

Get, significantly or continue to occur 3 fens

It is heavy or be interrupted to occur 2 fens when time thes be light

Gently or once in a while occur 1 fen

(5) dry mouth and throat

There is not 0 fen

Initiatively said 4 fens

Get, significantly or continue to occur 3 fens

It is heavy or be interrupted to occur 2 fens when time thes be light

Gently or once in a while occur 1 fen

(6) dysphoria with feverish sensation in the chest palms and soles

There is not 0 fen

Initiatively said 4 fens

Get, significantly or continue to occur 3 fens

It is heavy or be interrupted to occur 2 fens when time thes be light

Gently or once in a while occur 1 fen

(7) picture of the tongue

Body of the tongue is light red to have Tianjin 0 minute

Red tongue with a little fluid 2.5 minutes

(8) pulse condition

Not fast 0 minute of pulse condition

Thready pulse speed 2.5 minutes

(9) give birth in the double damp-phlegm

There is not 0 fen

Initiatively said 4 fens

Get, significantly or continue to occur 3 fens

It is heavy or be interrupted to occur 2 fens when time thes be light

Gently or once in a while occur 1 fen

(10) double qi depression to blood stasis

There is not 0 fen

Initiatively said 4 fens

Get, significantly or continue to occur 3 fens

It is heavy or be interrupted to occur 2 fens when time thes be light

Gently or once in a while occur 1 fen

Seven, curative effect determinate standard

(1) disease criterion

Judge that according to " combination of Chinese and Western medicine magazine " 1986 the 6th volumes o. 11th 682 pages " the screening rules of slow down aging Chinese medicine and clinical observation standards " the curative effect of medication standard is as follows:

Produce effects: the symptom total mark descends 〉=2/3; Effectively: the symptom total mark descends 〉=1/3; Invalid: symptom total mark and above-mentioned standard.

(2) curative effect determinate standard of hyperlipemia

Produce effects: the decline 〉=2/3 of symptom total mark or cholesterol and triglyceride decline 〉=40mg%; Low density lipoprotein, LDL decline 〉=70mg%.

Effectively: the symptom total mark descends more than 〉=1/3 or cholesterol and triglyceride decline 〉=20mg%; Low density lipoprotein, LDL decline 〉=35mg%.

Invalid: symptom total mark decline deficiency 〉=1/3 or cholesterol and triglyceride decline＜20mg%; Low density lipoprotein, LDL decline＜35mg%.

Eight, interpretation of result

Calculate two groups of treatment effective percentage (produce effects+effective) respectively, with card side (X) check analysis contrast, to estimate the curative effect of " ZWW ".

Nine, form is observed in clinical trial

See Table 2.

Illustrate:

1, clinical trial unit is no less than 3, and each hospital is no less than 100 examples, many 30 examples of matched group; Main disease is no less than 200 examples in 300 examples.

2, the test case is selected to adopt and is in hospital and clinic case, and clinic case is wanted strict its variable factor of control.

3, test whole results, gather, carry out statistical procedures and evaluation, write out formal new drug clinical experiment report by the clinical research responsible department.

Table 1 is respectively organized the experimenter and is numbered group numbering first 123567 11 12.13 15 16 17 21 22 23 25 26 27 31 second 48 14 18 24 28 first 32 33 35 36 37 41 42 43 45 46 47 51 52 53 55 56 57 61 69 second 34 38 44 48 54 58 64 first 63 65 66 67 71 72 73 75 76 77 81 82 83 85 86 87 91 92 93 second 68 74 78 84 88 98 first 95 96 101 102 103 105 106 107 111 112 113 115 116 117 second 104 108 114 118 124 128 first 121 122 123 125 126 127 131 132 133 135 136 137 141 142 143 second 134 144 148 first 145 146 147 151 152 153 155 156 157 161 162 163 second 154 158 164

Same numbering is carried out in 3 hospitals respectively, and wherein 2 hospitals observe treatment and organize 99 examples, matched group 33 examples; Another hospital observes treatment and organizes 102 examples, matched group 34 examples.

The professional national address of the clinical 1 experimental observation table admission number № name sex age body weight (kg) of table 2

Sings and symptoms (before and after the medication):

1, waist soreness (front and back) 2, vertigo and tinnitus (front and back)

3, seminal emission (front and back) 4, night sweat (front and back)

5, dry mouth and throat (front and back) 6, dysphoria with feverish sensation in the chest palms and soles (front and back)

7, red tongue with a little fluid (front and back) 8, thready pulse speed (front and back)

9, give birth to (front and back) 10, double qi stagnation blood stasis (front and back) differential diagnosis in tcm in the double damp-phlegm: after the preceding medication of medication: Western medicine diagnose: make a definite diagnosis the time: date PMI: the past medication: observe medication: the time started: date

Concluding time: date inspection item: the just conventional T-CHOL triglyceride of hematuria low density lipoprotein, LDL high density lipoprotein untoward reaction after the medication before the medication: 1, nauseating (front and back) 2, vomiting (front and back) 3, xanthochromia (front and back)

4, diarrhoea (front and back) 5, other (front and back)

Annotate: project all can the negative positive be represented in all brackets, all can actual numerical value represent that sings and symptoms one hurdle with 0,4,3,2,1 expression, is seen the symptom integral table according to the state of an illness for other all.

" ZWW " effect for reducing fat clinical observation on the therapeutic effect

Physical data

According to the clinical designing requirement of " ZWW " effect for reducing fat, select hyperlipemia case 300 examples, by 2: 1 at random clinical observation table be divided into observation group's 200 examples, matched group 100 examples are the inpatient, other data see table 1 for details.

Table 1

163 137 male 48≤0.05 ages of 52 woman of woman of the control group P of project observation group value sex (example) man (year) 62 ± 9.3 59 ± 7.5≤0.05 Syndrome Differentiation of Chinese Medicine disease (example) deficiency of liver-yin and kidney-yin 300 100＜0.01 phlegm of holding concurrently gives birth to 189 63＜0.05 high blood pressure brain of learning of qi stagnation blood stasis 111 37≤0.05 Western medicine diagnose (example) hyperlipidemia 300 100＜0.01 of holding concurrently in wet and move A 185 61≤0.05 coronary disease and angina pectoris 115 39≤0.05 that hardens

By table 1 as seen, observation group and matched group are debated aspect zero differences such as disease and Western medicine diagnose in sex, age, the traditional Chinese medical science.

Method

Medicine and administrated method and curative effect determinate standard are carried out according to the clinical designing requirement of " ZWW " effect for reducing fat.

The result

" ZWW " low dose of and heavy dose of group, vitamin E Nicotinate Capsules group TCM Syndrome Type curative effect relatively sees Table 2.

Low dose of and the heavy dose of group of table 2 " ZWW ", vitamin E Nicotinate group Syndrome in TCM

The type curative effect relatively

The hepatic and renal YIN deficiency is held concurrently and is given birth to the qi stagnation blood stasis total effective rate group of holding concurrently in the phlegm-damp

Example number enabledisable example number enabledisable example number enabledisable, (%) " ZWW " low dose of 100 78 22 63 50 10 37 23 14 is efficient, (%) 78 79.4 62.2 75.5 " ZWW " heavy dose of 200 191 9 126 119 7 74 61 13 are efficient, (%) 95.5 94.4 82.4 92.8VitE nicotinic acid resin capsules 100 63 37 65 38 27 35 18 17 are efficient, (%) 63 58.5 51.4 59.5P value≤0.05≤0.01≤0.05＜0.01

By table 2 as seen, in each TCM Syndrome Type, the effective percentage of " ZWW " heavy dose of group is the highest; The effective percentage of " ZWW " small dose group is higher than the vitamin E Nicotinate group.

" ZWW " low dose of and heavy dose of group, blood lipid level relatively sees Table 3 before and after the treatment of vitamin E Nicotinate Capsules group.

Low dose of and the heavy dose of group of table 3 " ZWW " is before the treatment of vitamin E Nicotinate group

Back blood lipid level is (mmol/L) relatively

" ZWW " low dose " ZWW " megavitamin E nicotinic acid resin project P value

n＝100 n＝200 n＝100 ( X±SD ) 6.27±0.98 6.36±0.79 6.21±0.67＞0.05 5.29±0.37 4.82±0.55 5.37±0.43P ≤0.05＜0.01 ≤0.05 0.93±0.89☆ 1.54±0.74 0.87±1.01☆ ≥0.05 ( X±SD ) 4.29±1.30 4.93±1.4 4.45±1.6 ≥0.05 3.01±0.84 2.91±0.39 3.21±0.71P ≤0.05＜0.01 ≤0.05 1.31±0.47 2.10±0.51 1.29±0.54＞0.05 ( X±SD ) 4.12±1.02 4.23±0.98 4.09±1.21＞0.05 2.98±1.26 2.09±1.09 2.89±1.30P ≤0.05＜0.01 ≤0.05 1.15±0.97 2.17±0.37 1.21±0.69 ≥0.05 ( X±SD ) 1.09±0.20 0.93±0.41 0.89±0.39 ≥0.05 1.19±0.37 1.27±0.21 0.9±0.23P ≥0.05 ≤0.01＞0.05 0.09±0.13★ 0.33±0.17 0.04±0.29★ ≥0.05

By table 3 as seen, low dose of and heavy dose of group before the treatment, cholesterol, triglyceride, low density lipoprotein, LDL and hdl concentration zero difference before the treatment of vitamin E Nicotinate group.After the treatment, the rising of cholesterol, triglyceride, the decline of low density lipoprotein, LDL content and hdl concentration is the most remarkable with " ZWW " heavy dose of group, and " ZWW " small dose group and vitamin E Nicotinate group zero difference.

" ZWW " low dose of and heavy dose of group, plasma fibrinogen content and serum fibrin degradation product (FDP) content relatively see Table 4 before and after the treatment of vitamin E Nicotinate group.

Plasma fibrinogen (mg/dl) and serum fibrin degradation product (FDP) content compare (μ g/ml) before and after big small dose group of table 4 " ZWW " and the treatment of vitamin E Nicotinate group

" ZWW " low dose " ZWW " megavitamin E nicotinic acid resin

Project P value

(X ± (3.56 ± 1.20 3.02 ± 1.31 5.29 ± 2.11P values＜0.05＜0.01 〉=0.05 reduction was worth 1.94 ± 1.07 2.13 ± 1.82 0.31 ± 1.10＜0.01 to n=100 n=200 n=100 fibrinogen after X ± SD) treatment front 5.50 ± 2.1 5.12 ± 1.9 5.32 ± 2.0 〉=0.05 was treated SD) to treat rear 413.2 ± 41.1 383.9 ± 51.2 415.9 ± 56.4P values of front 428.3 ± 43.3 409.6 ± 67.9 419.3 ± 47.1 〉=0.05 treatments≤0.05＜0.01＞0.05 reduction value, 15.7 ± 10.1 21.3 ± 14.1 3.8 ± 7.9≤0.01 fibrin degradation product (FDP)s

By table 4 as seen, " ZWW " low dose of and heavy dose of group, plasma fibrinogen and serum fibrin degradation product (FDP) content indifference before the treatment of vitamin E Nicotinate group.After the treatment, three combined amount significant differences, it is the most obvious to descend with the heavy dose group, and the rope E nicotinic acid resin group of supporting one's family does not have decline.

Untoward reaction

In this clinical trial process, find that " ZWW " has untoward reaction, blood, urine, just safeties such as routine and liver, renal function detect no abnormal change.

Conclusion

One, " ZWW " is for efficient, low toxicity blood fat reducing with improve the good medicine of Chinese and western medicine clinical symptoms;

Two, low dose of " ZWW " is identical with the vitamin E Nicotinate drug effect aspect blood fat reducing;

Three, " ZWW " can reduce plasma fibrinogen and serum fibrin degradation product (FDP) content, and vitamin E Nicotinate does not have this effect;

Four, heavy dose of " ZWW " has optimum curative effect, but and high density lipoprotein increasing content.

Claims (2)

1, a kind of medicine that has blood lipid regulation and reduce plasma fibrin is characterized in that; The proportioning of its each composition is;

Rhizoma Alismatis 85-95%

Myrrha 4-14%

Surplus is a chitosan.

2, a kind of medicine production technology as claimed in claim 1 is;

A, get Rhizoma Alismatis, Myrrha drying, coarse crushing;

B, get coarse powder and soak into 90% ethanol washing liquid, spend the night, dynamically lixiviate discards residue;

C, extracting liquid filtering reclaim ethanol, are concentrated into the thick paste shape, and after the adding chitosan was mixed, oven dry was pulverized 100 order fine powders and incapsulated below 70 ℃.