CN1634353A - Medicine for treating vasculitis, scleriasis and arteriosclerosis type lower limb vascular occlusion - Google Patents

Abstract

The invention relates to a medicine for treating vasculitis, scleriasis and arteriosclerosis type lower limb vascular occlusion, which is prepared from root of red rooted saliva, spatholobus stem, frankincense, myrrh, and curcuma aromatica through disintegrating into mesh fines, extracting with water, mixing proportionally to prepare tablet and capsule.

Description

A kind of treatment vasculitis, scleroderma and arteriosclerosis lower extremities vascular occlusion disease drug

Technical field

The present invention relates to the pharmaceutical composition of a kind of blood circulation promoting and blood stasis dispelling, dredge the meridian passage, particularly relating to a kind of is the endo-medicine with blood circulation promoting and blood stasis dispelling, dredge the meridian passage effect that raw material is made with the vegetable Chinese herbal medicine, can be used in the Chinese patent medicine and the preparation thereof of treatment vasculitis, scleroderma and arteriosclerosis lower extremities vascular occlusion disease.

Background technology

At present, disclosed about treatment vasculitis, scleroderma and arteriosclerosis lower extremities vascular occlusion disease drug and preparation thereof, arranged the October 16 nineteen ninety applying date, and publication number 1060605 " a kind of manufacture method of strong thrombus-dissolving capsule " is made up of heavy dose of Chinese medicines such as Radix Angelicae Sinensis, Flos Carthami, Hirudo, Semen Strychni; 2000 applyings date December 1 day is arranged, and it is the medicine for external use of being made by Cornu Saigae Tataricae, Cornu Cervi, Cornu Bubali, Radix Ginseng, Omphalia, Radix Puerariae, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Calomelas, Moschus that publication number 1304763 " is treated sclerodermatous medicine and preparation method thereof "; March 15 2002 applying date, it is that raw material is formed with Radix Panacis Quinquefolii, Radix Scrophulariae, Flos Lonicerae, Pheretima, stir-baked SQUAMA MANITIS, Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, Caulis Akebiae, Medulla Tetrapanacis, Semen Cuscutae, Fructus Psoraleae, Rhizoma Curculiginis, Fructus Ligustri Lucidi, Carapax Trionycis (processed), Bulbus Lilii, Radix Asparagi, Fructus Lycii, Fructus Gardeniae, the Radix Astragali, Radix Adenophorae (Radix Glehniae), the Rhizoma Anemarrhenae, Herba Violae, Caulis Spatholobi, Stigma Croci, Spina Gleditsiae, Rhizoma Corydalis, Eupolyphaga Seu Steleophaga, Radix Angelicae Sinensis, Scolopendra, Radix Rehmanniae Preparata, the Radix Paeoniae Alba, Hirudo for publication number 1369297 " 'Sishen Tongmai ' mixture and preparation method thereof ", and flavour of a drug are more.Existing in a word medicine medicine for external use accounts for certain proportion, and the oral medicine flavour of a drug are more, and the manufacturing cost height, also contains toxic component in the medicine that has.

Summary of the invention

So the object of the invention is treated the endo-medicine and the preparation thereof of vasculitis, scleroderma and arteriosclerosis lower extremities vascular occlusion disease safely and effectively in that make existing prescription flavour of a drug with the Chinese crude drug of meticulously selecting few.

In order to reach the foregoing invention purpose, solution of the present invention is based on motherland's medical science to vasculitis, scleroderma and pathogenetic understanding of arteriosclerosis lower extremities vascular occlusion disease and Therapeutic Principle, screening blood circulation promoting and blood stasis dispelling, dredge the meridian passage Chinese crude drug are according to the theory of Chinese medical science prescription.

Medicine of the present invention also can be made (consumption is a weight portion) medicament by following component:

Radix Salviae Miltiorrhizae 20-30 part Caulis Spatholobi 20-30 part Radix Curcumae 5-15 part

Olibanum 2-6 part Myrrha 2-6 part

The optimum weight proportioning of medicine of the present invention is:

10 parts of 25 portions of Radix Curcumaes of 25 portions of Caulis Spatholobis of Radix Salviae Miltiorrhizae

4 parts of 4 parts of Myrrhas of Olibanum

Medicine of the present invention is characterized in that said medicament is a said dosage form on any pharmaceutics.

Medicine of the present invention is characterized in that said medicament is tablet, capsule.

With above-mentioned each component preparation cost invention medicine production method be: Olibanum, Myrrha, turmeric powder are broken into fine powder, Radix Salviae Miltiorrhizae, Caulis Spatholobi are used water extraction three times, 1.5 hours for the first time, second and third time 1 hour, each 98-102 ℃ of water temperature of extracting, extracting solution filters, and merging filtrate is evaporated to the thick paste of relative density 1.35-1.40 (60 ± 5 ℃ of heat are surveyed); Thick paste adds Olibanum, Myrrha, Radix Curcumae fine powder, and mixing is made bulky grain, vacuum drying, and dry substance is ground into fine powder, and mixing is made said dosage form on any pharmaceutics.

Treatment vasculitis of the present invention, scleroderma and arteriosclerosis lower extremities vascular occlusion disease drug (also claim " vascular tablet for recovery ") studies have shown that through pharmacodynamic experiment research, acute toxicity and long term toxicity test data and clinical etc. have blood circulation promoting and blood stasis dispelling, the dredge the meridian passage effect, remarkable to treating above-mentioned curative effect of disease, and have no side effect; Now experimentation is described below.

The pharmacodynamic experiment data that the vascular tablet for recovery is relevant with therapeutical effect

Cure mainly according to vascular tablet for recovery function, the relevant zoopery of design, the result is as follows:

1 experiment material

Animal: rat is purchased the laboratory animal portion in Beijing Medical University.

Mice is purchased the animal housing in Medical University Of Tianjin.

Medicine: vascular tablet for recovery Tianjin Tongrentang Co., Ltd. (former Tianjin Tongrentang Pharmaceutical Factory) provides.

It is 6g/kg, 3g/kg, 1.5g/kg that dosage is established in this experiment.

2 methods and result

2.1 influence to mouse blood viscosity and erythrocyte electrophoresis

Mice, Kunming kind 20 ± 2g, half and half, 60 of male and female.Be divided into 4 groups at random, matched group is given consubstantiality hydrops, successive administration 10 days, and after the last administration 1 hour, extract eyeball and get blood, survey whole blood viscosity and erythrocyte electrophoretic time respectively, the results are shown in Table 1.

Table 1: to the influence of mice whole blood viscosity (ratio) and erythrocyte electrophoretic time

Group	Number of animals	Dosage	Whole blood viscosity (ratio)	Erythrocyte electrophoretic time (S)
					Matched group	??15		??4.26±0.7	???14.6±3.7
High dose	??15	????6g/kg	??3.47±0.31 *	???10.5±3.1 *
					Middle dosage	??15	????3g/kg	??3.59±0.37 *	???11.2±2.6 *
Low dosage	??15	????1.5g/kg	??3.96±0.6 *	???13.5±4.1

Each experimental group is compared with matched group ^*P＜0.05

2.2 influence to the rat platelet aggregation test

Male 50 of rat, body weight 200-220g.In each one week of experimental group continuous oral administration, dosage and grouping situation see Table 2.Prepare healthy rat platelet rich plasma (PRP) routinely, platelet poor plasma (PPP), biochemical instrument factory measures the platelet aggregation percentage rate with B-S631 type Beijing.The results are shown in Table 2.

Table 2: to the X ± SD that influences of rat platelet aggregation

Group	Number of animals	Dosage	Maximum agglutination rate %	Assemble suppression ratio %
					The normal saline group	??10		????46±12
The aspirin group	??10	????40mg/kg	????28±16 **	??39.1
					High dose	??10	????6g/kg	????29±10 **	??36.9
Middle dosage	??10	????3g/kg	????32±11 *	??30.4
					Low dosage	??10	????1.5g/kg	????40±17	??17.4

Each reagent group is compared with the normal saline group ^*P＜0.01 ^*P＜0.05

2.3 to the thrombotic influence of rat experiment

The Wistar rat, the male and female dual-purpose, female person is infertile, 240 ± 20g, one week of continuous oral administration, after the last administration 1 hour, lumbar injection pentobarbital sodium (40mg/kg) anesthesia, it is fixing to lie on the back, and tracheal intubation is separated left neck and is reached right common carotid artery outward.Get the sleeve pipe that three sections polyethylene tubes are formed, its stage casing is equipped with the 4# silk thread that a long 6cm weighs.Be full of polyethylene tube with heparin-saline solution, it is total that the fixed end sleeve pipe of silk thread is inserted neck, and the other end inserts external jugular vein, injects heparin (50 μ I) by the abdomen vein, and behind the open blood flow 15min, middle immediately Herba Clinopodii takes out silk thread rapidly and weighs.Gross weight deducts silk thread weight and is wet weight of thrombus, by formula calculates thrombosis suppression ratio (the grouping situation sees Table 3).

Table 3: to the thrombotic X ± SD that influences of rat experiment

Group	Number of animals	Dosage	Wet weight of thrombus (mg)	Suppression ratio %
					The normal saline group	??10		??22.6±3.1
The aspirin group	??10	??40mg/kg	??14.0±2.9 *	????46.9
					High dose	??10	??6g/kg	??17.2±2.7 *	????28.3
Middle dosage	??10	??3g/kg	??18.5±1.8	????22.6
					Low dosage	??10	??1.5g/kg	??18.9±1.3	????16.4

Each reagent group is compared with the normal saline group ^*P＜0.05

2.4 influence to Oleum Tiglii induced mice auricle inflammation

With the male mice random packet of body weight 18-22g, the grouping situation sees Table 4, continuous oral medicine 7 days, and even drop Oleum Tiglii mixing causes the every ear of scorching liquid 0.05ml/ in the wide both sides of auris dextra after 1 hour in the last administration, gets auricle with the 9mm card punch and weighs.Difference with left and right sides auricle weight is the swelling degree, the results are shown in Table 4.

Table 4: to the X ± SD that influences of mice Mus ear swelling

Group	Number of animals	Dosage	Average swelling degree (mg)	Suppression ratio %
					Normal saline	??15		????22.4±7.5
Hydrocortisone	??15	??20mg/kg	????9.8±3.3 **	????56.3
					High dose	??15	??6g/kg	????14.3±5.2 **	????36.1
Middle dosage	??15	??3g/kg	????17.7±5.7	????22.1
					Low dosage	??15	??1.5g/kg	????19.2±6.2	????16.5

Each reagent group is compared with the normal saline group ^*P＜0.01

2.5 influence to clotting time

Get 40 of healthy mices, divide 4 groups at random, every day, oral administration was continuous 5 days, and after the last administration 1 hour, get blood with internal diameter 1mm capillary glass tube insertion rathole ball rear vein beard, to put in the glass capillary, thrombosis reaches 5cm.Fractureed every 30 seconds one section in capillary tube is checked to have or not the blood clotting silk to occur, and calculating takes a blood sample to from glass capillary the time of blood clotting silk occurs, is clotting time.The results are shown in Table 5.

Table 5: to the X ± SD that influences of clotting time of mice

Group	Number of animals	Dosage	Clotting time (branch)
				Matched group	????10		????1.3±0.38
High dose	????10	????6g/kg	????0.86±0.25 *
				Middle dosage	????10	????3g/kg	????0.94±0.17 *
Low dosage	????10	????1.5g/kg	????1.02±0.18

Each experimental group is compared with matched group ^*P＜0.05

2.6 influence to rat hindlimb muscular tissue blood flow

Get Wistar rat male and female dual-purpose, 40, one week of continuous oral medicine (the grouping situation sees Table 6) is in last administration pentobarbital sodium (40mg/kg) anesthesia after 1 hour, lie on the back and fixedly cut off upside skin in the left hind, carefully, be connected in RBF-II electrolytic people tissue blood flow's instrument (Japan), stablized 10 minutes first processed bipolar input casket, press literature method and measure (the electrolysis blood flow 20mA of tissue blood flow, electrolysis time 25S, sensitivity I V), the results are shown in Table 6.

Table 6: to the X ± SD that influences of rat hindlimb muscular tissue blood flow

Group	Number of animals	Dosage	The amount ml/100/min of hind leg tissue blood flow
				Matched group	????10		????32.1±10.1
High dose	????10	????6g/kg	????46.2±12.4 *
				Middle dosage	????10	????3g/kg	????40.1±14.13
Low dosage	????10	????1.5g/kg	????36.0±11.0

Each experimental group is compared with matched group ^*P＜0.05

2.7 analgesic experiment (mouse writhing experiment)

Get 40 of Kunming mouses, 18-20g, female, normal saline (0.2ml/10g), aspirin (0.2g/kg) reagent three dosage (6g/kg, 3g/kg, 1.5g/kg), continuous 5 days of oral administration, in the last administration after 1 hour, lumbar injection 5% acetic acid solution, every of 0.2ml/, the observation mice is turned round the number of times of body in 15 minutes, the results are shown in Table 7.

Table 7: to the X ± SD that influences of acetic acid induced mice writhing response

Group	Number of animals	Dosage	Turn round body number of times X ± SD in 15 minutes
				Normal saline	????10		?30.1±8.1
Aspirin	????10	????0.2g/kg	?20.1±7.1 *
				High dose	????10	????6g/kg	?24.2±5.2 *
Middle dosage	????10	????3g/kg	?25.1±6.3

Low dosage

????10

??1.5g/kg

????27.6±8.7

Each experimental group with the normal saline group is compared ^*P＜0.05

3 brief summaries

This experimental result confirms that " vascular tablet for recovery " has the vitro inhibition rat suppository and form and antiplatelet aggregative activity, can reduce whole blood viscosity and erythrocyte electrophoretic time, increases the rat hindlimb blood flow, reduces clotting time; And antiinflammatory, analgesic experiment also there is certain effect.Above experimental result shows that the true tool blood circulation promoting and blood stasis dispelling of this medicine improves the blood circulation effect, helps the rehabilitation and the doing well,improving of illness such as vasculitis, scleroderma.

Vascular tablet for recovery acute toxicity test in mice

1 experiment material

1.1 animal: Kunming kind healthy mice 18-22g.Mice is divided into three groups at random, and 10 every group, male and female half and half are provided by Chinese Academy of Medical Sciences animal groups center.

1.2 medicine: vascular tablet for recovery Tianjin Tongrentang Co., Ltd. (former Tianjin Tongrentang Pharmaceutical Factory) provides.

2 experimental techniques

Divide 28.8g/kg, 14.4g/kg, three dosage groups of 7.2g/kg, be used for the oral route experiment.Earlier the mice fasting after 16 hours, is observed a week after a gastric infusion 0.3ml/10g (mice body weight) administration, the toxic reaction situation of record animal is also carried out the dead animal postmortem.Press the LD50 that the bliss method is calculated oral route.

3 experimental results

Acute none animal dead as a result of the oral route of vascular tablet for recovery, the diet of animal, drinking-water are normal, fur gloss, bodily form stalwartness.Sacrifice of animal is carried out gross necropsy, no abnormal discovery.Because be subjected to the restriction of drug level and volume, oral LD50 can not measure.The maximum tolerated dose of oral way is 28.8g/kg, is 240 times of clinical application amount.

Vascular tablet for recovery rat long term toxicity test

1 experiment material

1.1 animal: the Wistar rat, 6 ages in week, totally 80, the male 86 ± 10g of body weight, n=40 is only, and is female, 87 ± 10g, n=40; Available from animal cultivation institute of Chinese medical courses in general institute.

1.2 medicine: vascular tablet for recovery Tianjin Tongrentang Co., Ltd. (former Tianjin Tongrentang Pharmaceutical Factory) provides, with the administration of distilled water preparation suspension oral gavage.

1.3 raising condition: 5 in every cage, male and female divide supports 22 ± 2 ℃ of room temperatures.Feeds utilized available from the Tianjin animal center.Drinking water is a tap water.

2 experimental techniques

2.1 dosage grouping: rat is divided into four groups at random, 20 every group, male and female half and half.

A: high dose: 24g/kg is to be used for 200 times of clinical treatment amount.

B: middle dosage: 12g/kg

C: low dosage: 6g/kg

D: matched group: the distilled water that waits capacity.

2.2 route of administration and time: gastric infusion, volume are 2ml/100g, and every day, the morning, 8:30-9:30 was administered once, 6 times weekly, and successive administration 3 months (90 days).

2.3 observe and detect index

A. overview: behavioral activity, outward appearance sign, feces character, appetite and body weight change, experiment before measurement body weight, routine weighing after the administration.

B. blood plasma is learned index: red blood cell count(RBC), total white blood cells and classification hemoglobin, platelet, clotting time.

C. blood parameters: glutamic oxaloacetic transaminase, GOT, glutamate pyruvate transaminase, alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine (CREA), total protein (TP), albumin (ALB), blood glucose (GLU), total bilirubin (T-BIL), T-CHOL (T-CHO).

D. system becomes celestial and histopathologic examination

After used rat becomes celestial and checks, take off the row histoorgan and do histological examination, comprise the heart, liver, spleen, lung, kidney, brain, stomach, duodenum, rectum, hypophysis, thymus, thyroid, adrenal gland, pancreas, uterus, ovary, bladder, prostate, testis.Wherein the heart, liver, spleen, lung, kidney, brain, adrenal gland, ovary, testis are weighed, calculate organ coefficient.

E. every index determining time: test after the 90th day and drug withdrawal observed for 2 weeks,, survey the relevant above-mentioned every index of inspection respectively according to trustee's requirement.

3 experimental results

3.1 overview: activities in rats, food-intake normal, each organizes the body weight no significant difference.See Table 1.

3.2 blood biochemical analysis: compare successive administration 90 days and no significant differences (P＞0.05) after 2 weeks of drug withdrawal with matched group.See Table 2.

3.3 hematological examination: compare the equal no significant difference of the every index of each administration group (P＞0.05) with matched group.See Table 3.

3.4 internal organs inspection: it is all normal that each organizes every internal organs system, and no significant difference (P＞0.05).See Table 4-5.

3.5 histopathologic examination

A. macroscopy

Matched group and each dosage group fur are normal, and crissum is not seen secretions, and breast, abdomen are not seen pneumatosis, hydrops, and serous coat is smooth.Do not see the petechia, each internal organs position is as usual, and macroscopy does not see that work becomes.Cut off skull, pleura and brain also do not see that work becomes.

B. mirror is checked down

Matched group and high, medium and low three each internal organs of dosed administration group there is no work and become.Heart: each is organized cardiac muscle and is not seen hypertrophy, atrophy and fracture, and a matter is not seen cell infiltration and fiber

Hamartoplasia is not seen exudate, and the arteria coronaria blood vessel is not seen significant change.

Lungs: each organizes Mus bronchus at different levels and each LA there is no the work change, and each blood vessel of lung does not also see that work becomes.

Liver: tunicle is smooth, and liver central authorities venule, the little arteriovenous of liver and little bile duct there is no work and become.Hepatocyte does not see degeneration, necrosis, does not see connective tissue proliferation.

Kidney: tunicle is smooth, skin medullary substance boundary clear, and glomerule is not seen minimizing, hypertrophy or fibrosis, and nearly Distal convoluted tubule and collecting tubule epithelial cell are not seen degeneration, necrosis, do not see cast and calculus in the tube chamber, and the transitional cell carcinomo of renal pelvis epithelium is smooth.

Pancreas: leaflet structure exists, and the exocrine portion that serous acinus and conduit constitute in the lobule does not see that work becomes, and is dispersed in the islet cells group between exocrine gland, differs in size, and cell number differs, and does not see significant difference between each group.

Spleen: tunicle is not seen and is thickened, red white pulp clear in structure, and splenic nodule, lymph sheath, snius lienis, splenic cords etc. do not see that work becomes, and spleen central authorities small artery do not see and reduces and increase, and tube wall is not seen and is thickened.There is no work between each group such as brain, stomach, duodenum, rectum, hypophysis, thymus, thyroid and lymph node, uterus, ovary, bladder, prostate becomes.

4 brief summaries

80 of Wistar rats are selected in experiment for use, and male and female half and half are divided into four groups at random.Dosage is respectively 200 times, 100 times, 50 times of adult's clinical dosage.In 2 weeks after administration observation 90 days and the drug withdrawal, each treated animal ordinary circumstance does not change, and animal sign, body weight, biochemical indicator, hemogram, organ coefficient and pathological observation there is no unusually, shows that it is safe and reliable that this medicine uses.

Table 1: to the influence of rat body weight

Group		Matched group	High dose	Middle dosage	Low dosage
						Body weight is observed X ± S D ︵ g ︶ before and after the administration	0 week	??88.2±9.8	??87.8±7.9	??87.5±8.9	??86.9±9.1
1 week	??108.6±9.8	??99.8±10.3	??108.4±8.7	??101.3±9.9
					3 weeks		??134.8± ????16.1	??131.2± ????13.5	??129.4± ????16.8	??131.9± ????16.1
4 weeks	??153.3± ????16.9	??143.8± ????16.5	??142.2± ????11.6	??148.2± ????17.1
					5 weeks		??169.2± ????16.1	??158.8± ????16.3	??153.4± ????16.7	??162.1± ????14.4
6 weeks	??182.8± ????16.1	??175.2± ????18.8	??177.9± ????15.1	??180.4± ????16.2
					7 weeks		??200.4± ????14.4	??192.7± ????19.8	??198.7± ????21.8	??198.2± ????21.6
8 weeks	??223.7± ????16.2	??212.3± ????22.6	??219.8± ????19.4	??218.3± ????21.7
					9 weeks		??239.4± ????24.1	??231.4± ????20.5	??238±23.5	??234.5± ????24.6
10 weeks	??249.1± ????28.2	??240.4± ????26.9	??244.7± ????32.1	??243.4± ????24.8
					11 weeks		??253.2± ????32.2	??253.6± ????23.4	??253.2± ????28.6	??250.8± ????18.1
12 weeks	??261.4± ????27.6	??259.3± ????32.1	??261.8± ????23.6	??259.6± ????23.6
					14 days n=6 after the drug withdrawal		14 weeks	??265.5± ????31.2	??260.9± ????27.3	??270.1± ????22.6	??263.8± ????28.1

Table 2: to the X ± SD that influences of the every biochemical indicator of rat

Each dosage group and matched group all do not have significant difference p＞0.05 by statistics

Table 3: to the X ± SD that influences of rat hemogram, leukocyte differential count and clotting time

Each dosage group and matched group all do not have significant difference p＞0.05 by statistics

Table 4: the continuous oral administration after 90 days to the X ± SD that influences of each organ coefficient of rat

n＝14

Table 5: drug withdrawal after 14 days to the X ± SD that influences of each organ coefficient of rat

n＝6

Table 4,5 is respectively organized, every organ coefficient is all normal, and no significant difference (p＞0.05)

The clinical observation of vascular tablet for recovery treatment chronic arteria occlusion disease

The periphery artery occlusion disease mainly comprises thromboangiitis obliterans (being called for short TAO) and arteriosclerosis obliterans's (being called for short ASO), is a kind of clinically common refractory disease.Select for use the vascular tablet for recovery to treat this type of disease 300 examples, and treat 150 examples with Herba Erigerontis tablet and contrast, curative effect is better, and observed result is as follows.

1 clinical data

1.1 sick kind the: vascular tablet for recovery observation group 300 examples, ASO 180 examples, TAO 120 examples; Herba Erigerontis tablet matched group 150 examples, ASO 90 examples, TAO 60 examples.

1.2 diagnosis and standard by stages

The standard that ASO and TAO diagnosis and standard are by stages all formulated according to Chinese combination of Chinese and Western medicine peripheral vascular disease Professional Committee (clinically assembles 1990; 5 supplementary issue 39-40) level " new Chinese medicine clinical guidance principle ".Two groups sick plants and pathological changes sees Table 1 by stages.

Table 1: the sick kind of observation group and matched group reaches and compares by stages

The sick stadium of planting

The ASO TAO I phase II phase III phase

Observation group 180 120 90 159 51

Matched group 90 60 47 73 30

Two groups of contrast zero differences

1.3 physical data

Observation group's 300 examples, man 180, woman 120, the oldest person 76 years old, reckling 27 years old, average 58.6 years old; Matched group 150 examples, man 90, woman 60, the oldest person 75 years old, reckling 24 years old, average 61.3 years old.The course of disease, observation group is the longest 52 months, the shortest person 4 months, average 14.6 months; Matched group is the longest 46 months, the shortest person 3 months, average 15.4 months, two groups of ordinary circumstance contrast zero differences.

2 observational techniques and observation item

2.1 observational technique

Grouping: clinically be divided into two groups at random, observation group and matched group.

Medicine for treatment: the oral vascular tablet for recovery of observation group (Tianjin Tongrentang Co., Ltd. provides), matched group oral Breviscapine sheet (Chinese Academy of Medical Sciences's hematopathy institute hematopathy hospital pharmacy provides).

Therapeutic Method: the oral vascular tablet for recovery of observation group, each 8, every day 3 times, continuous six weeks back evaluation curative effect; Matched group oral Breviscapine sheet, each 40 milligrams, every day 3 times, continuous six weeks back evaluation curative effect.There is ulcer person to keep routine to change dressings.

2.2 observation index

Symptom and sign: mainly observe pain, creeping chill, limping and ulcer, for ease of comparing, the unified column index standard of pressing is marked.

A limbs pain (general analgesic refers to non-dolantin, morphine class addictive drug, as salicylic acid etc.)

0 minute: no pain.

1 minute: idol had pain, can remember when being asked.

2 minutes: pain often occurred but can tolerate, and need not or use general analgesic by chance.

3 minutes: often take general analgesic.

4 minutes:, be difficult to alleviate with general analgesic because of pain influence sleep.

The b intermittent claudication

Lower limb: by normal speed walking (60-70 rice/minute), travel distance before the medication relatively, measure medication after walking prolong distance; With hundred meters be unit, round up.

0 minute: walk＞500 meters no intermittent claudication.

1 minute: walking 400-499 rice had pain.

2 minutes: walking 300-399 rice had pain.

3 minutes: walking 100-299 rice had pain.

4 minutes: rest pain, can't walk, or walk＜100 meters, pain is arranged.

Upper limb: two arm held upwards, with 60 hold/minute frequency, both hands are clenched fist, and measure the time before and after the medication.Minute to be unit, less than was disregarded in 30 seconds, surpassed 30 seconds by 1 minute.

0 minute: perseveration＞5 minute, no pain.

1 minute:＜5 minutes, there was pain perseveration＞4 minute.

2 minutes:＜4 minutes, there was pain perseveration＞3 minute.

3 minutes:＜3 minutes, there was pain perseveration＞1 minute.

4 minutes: rest pain, can't go up act; Or perseveration＜1 minute, pain is arranged.

C limbs creeping chill

0 minute: do not have.

1 minute: patient's idol is stated the limbs of getting involved the cold of sending out and the sensation of being afraid of cold.

2 minutes: the patient often states the limbs of getting involved the cold and the cold sensation of sending out.

3 minutes: the limbs of the getting involved sensation that obviously cools, need to adopt the partial insulation measure, symptom can obtain alleviation to a certain degree.

4 minutes: the limbs of the getting involved sensation that obviously cools, adopt above-mentioned measure not have obvious improvement.

The d ischemic ulcer

Before the medication

0 minute: no ulcer and ulcer tendency.

2 minutes: ulcer tendency (comprising that skin color changes callosity, local redness etc.) is arranged.

4 minutes: ulcer.

After the medication

0 minute: healing fully.

1 minute: the ulcer area dwindled more than 50%.

2 minutes: the ulcer area dwindled 20-50%.

3 minutes: the ulcer area change was in ± 20%.

4 minutes: the ulcer area increased more than 20%.

Laboratory indexes: mainly observe whole blood opaque fibronectin content, cholesterol and triglyceride.

Rheography: observe extremity PBF and ankle upper arm index.

3 observed results

3.1 clinical index improvement situation sees Table 2, table 3, table 4, clinical index has apparent in view improvement after observation group and the treatment of control group as can be seen from the table, and table 2 shows, observation group improves at index aspect pain and the limping and is better than matched group.

Table 2: several clinical indexs compare X ± S before and after observation group's treatment

Pain creeping chill limping ulcer

Treat preceding 2.48 ± 0.77 1.86 ± 0.78 2.47 ± 1.06 2.79 ± 0.97

Treatment back 1.30 ± 0.54 ^*1.29 ± 0.68 ^*1.53 ± 0.85 ^*0.74 ± 0.36 ^*

Annotate: contrast before treatment back and the treatment ^*P＜0.01, ^*P＜0.05.

Table 3: several clinical indexs compare X ± S before and after the treatment of control group

Pain creeping chill limping ulcer

Treat preceding 2.09 ± 0.96 1.78 ± 0.67 2.31 ± 1.37 2.70 ± 1.12

Treatment back 1.54 ± 0.77 ^*1.21 ± 0.57 ^*1.74 ± 0.96 ^*0.53 ± 0.41 ^*

Annotate: contrast before treatment back and the treatment ^*P＜0.01, ^*P＜0.05.

Table 4: two groups of treatment back index decreased averages compare X ± S

Example number pain creeping chill limping ulcer

Observation group 300 0.98 ± 0.47 0.61 ± 0.36 0.95 ± 0.34 2.01 ± 0.47

Matched group 150 0.57 ± 0.42 ^*0.59 ± 0.40 0.61 ± 0.31 ^*1.94 ± 0.51

Annotate: observation group and matched group contrast ^*P＜0.05.

3.2 laboratory indexes improves situation

Table 5, table 6 are represented the variation of hemorheology and blood lipid level before and after observation group and the treatment of control group respectively, in the table result show two groups after the whole blood viscosity treatment, make moderate progress, surplus having no significant change, two groups of decline averages are more meaningless.

Table 5: the hemorheology index compares X ± S before and after observation group's treatment

Whole blood viscosity Fibrinogen cholesterol triglyceride

Treat preceding 14.76 ± 2.95 3.67 ± 1.21 7.85 ± 3.59 2.45 ± 0.49

Treatment back 11.50 ± 1.84 ^*3.74 ± 1.34 8.14 ± 4.18 2.19 ± 0.51

Annotate: contrast before treatment back and the treatment ^*P＜0.05.

Table 6: the hemorheology index compares X ± S before and after the treatment of control group

Whole blood viscosity Fibrinogen cholesterol triglyceride

Treat preceding 13.96 ± 3.73 3.87 ± 1.35 8.14 ± 2.98 2.27 ± 0.37

Treatment back 10.49 ± 1.74 ^*3.76 ± 1.73 8.39 ± 3.47 2.10 ± 0.30

Annotate: contrast before treatment back and the treatment ^*P＜0.05.

3.3 the variation of rheography index

Table 7, table 8 represent that respectively the blood flow of observation group and matched group front and back changes and ankle upper arm index improves situation, as can be seen, after two groups of treatments certain improvement effect is arranged all, but two class index rising averages compare zero difference from two tables.

Table 7: blood flow (ml) and ankle upper arm index index compare X ± S before and after observation group's treatment

Upper limb lower limb ankle upper arm index

About about about

Treat preceding 6.42 ± 7.12 ± 4.21 ± 3.98 ± 0.73 ± 0.68 ±

2.89???2.57??1.96???1.73???0.15???0.11

Treatment back 8.13 ± 8.54 ± 5.93 ± 5.74 ± 0.88 ± 0.87 ±

2.10 ^*?2.61 ^*1.84 ^*1.96 ^*?0.19 ^*0.16 ^*

Annotate: contrast before treatment back and the treatment ^*P＜0.05.

Table 8: blood flow (ml) and ankle upper arm index index compare X ± S before and after the treatment of control group

Upper limb lower limb ankle upper arm index

About about about

Treat preceding 6.71 ± 7.33 ± 4.59 ± 5.97 ± 0.69 ± 0.64 ±

2.93????2.31????2.01???2.73????0.18????0.13

Treatment back 8.29 ± 8.67 ± 6.32 ± 7.82 ± 0.86 ± 0.85 ±

2.24 ^*?2.14 ^*??2.14 ^*?2.97 ^*??0.17 ^*?0.11 ^*

Annotate: contrast before treatment back and the treatment ^*P＜0.05.

3.4 efficacy analysis

The standard of formulating according to Chinese combination of Chinese and Western medicine peripheral vascular disease Professional Committee (clinically assembles 1990; 5 supplementary issue 39-40) be divided near more, produce effects, effective, invalid, two groups of curative effects relatively see Table 9, as can be seen from Table 9 two groups of curative effect zero differences.

Table 9: two groups of Comparison of therapeutic

The example number is produce effects enabledisable total effective rate closely more

Observation group 300 39 (12.8%) 141 (47.1%) 107 (35.8%) 13 (4.3%) 95.7%

Matched group 150 17 (11.14%) 60 (40%) 64 (42.9%) 9 (5.7%) 94.3%

3.5 side reaction

No matter be observation group or matched group, all do not find untoward reaction, none example is because of the untoward reaction drug withdrawal, before and after treatment all routine examination blood, urine, just routine and hepatic and renal function are all no abnormal.

4 brief summaries

4.1 from observed result, observation group's vascular tablet for recovery treatment ASO.TAO curative effect is more remarkable, total effective rate is 95.7%, cure-remarkable-effectiveness rate is 59.9%, all, pain, creeping chill, limping, ulcer index are improved aspect very obviously (p＜0.01 or p＜0.05) a little more than 94.3% and 51.4% of matched group Herba Erigerontis tablet.

4.2 observation group's vascular tablet for recovery has apparent in view improvement effect (p＜0.05) to LBF and ankle upper arm index, blood viscosity is had certain improvement effect (p＜0.05), but Fibrinogen, cholesterol, triglyceride are not had obvious improvement effect.

4.3 observation group and matched group are not all found side reaction in drug administration process, to blood, urine, just three big conventional regulating liver-QI kidney function test show that the vascular tablet for recovery does not have influence to above-mentioned inspection index.

In sum, the vascular tablet for recovery is a kind of the cheap of periphery artery occlusion disease for the treatment of, and the pure Chinese medicinal preparation of taking convenience has clinically and uses prospect comparatively widely.

The observation of curative effect of vascular tablet for recovery treatment local scleroderma 84 examples

Local scleroderma also belongs to the connective tissue disease category, and whether it and systemic sclerosis belong to same disease, and arguement is still arranged at present.The etiology unknown of primary disease though there is different understanding in each family, does not all have sure conclusion.

From clinical and laboratory observation, the local scleroderma pathological changes is mainly invaded local skin, subcutaneous tissue, muscle and sick district or the contiguous joint of decreasing, severe patient often causes dysfunction or disabled deformity, influence is grown and is reached to disability, but generally do not have the internal organs organic lesion, the person is rare so influence life.

About the treatment of primary disease, though record several different methods on the document, curative effect is all not obvious.Inst. of Hematology, Chinese Academy of Medical Sciences is from year March in June, 1962 to 1966, under the policy of the combination of Chinese and Western medicine instructs,

Under the sclerodermatous enlightenment of vascular tablet for recovery therapy system, use vascular tablet for recovery treatment local scleroderma 84 examples, obtained comparatively satisfied curative effect, now therapeutic outcome is summarized as follows.

1 clinical data

1.1 age and sex

In this group patient 84 examples, male's 34 examples, women's 50 examples.Age of onset 1-60 year is not waited, and average age of onset 15 years old is seen so that person below 10 years old is more, and totally 38 examples account for 45%.The course of disease is different in size, and two did not wait in thoughtful 17 years.

Table 1: all ages and classes of local scleroderma and morbidity

Age	??∽10	??∽20	??∽30	??∽40	??∽50	??∽60
							The example number	??38	??20	??18	??3	??2	??1

1.2 typing with by stages

The performance of local scleroderma form differs, and grown form is speckle shape, band shape, and the band shape that betides head is called the sword cut type, and two kinds of form persons all have multiple case.Speckle shape type 23 examples in 84 examples, ribbon type 26 examples, sword cut type 27 examples, multiple types person's 8 examples.

Local scleroderma also have clinically swelling, sclerosis, atrophy by stages because the subjective symptoms of primary disease is not obvious, not necessarily for swelling or sclerosis stage, be in the atrophy stage when 6 example discoveries are arranged in this group case when therefore finding clinically.

Skin turgor is non-pitting, during skin sclerosis then skin lesion cured sample gloss takes place, the rhicnosis rareness is difficult for pinching, the sick severe patient that decreases, sclerosis is dark normal fixing and can not pinching.The equal atrophy attenuation of skin and subcutaneous tissue during atrophy, veins beneath the skin is many obviously as seen, but is fixed in muscle, skeleton more, the skin poor mobility, elastic force significantly goes down.

Often there is the intensification of pigment in the skin damage district or takes off mistake, also has mottled hypopigmentation to occur and the person that presents in the graniphyric in the skin lesion that color of the leather is deepened.Big while of skin appendages is impaired, local alopecia, and sweat gland, sebaceous gland atrophy, hypofunction causes skin lesion district drying, lossless and lose normal moist.The deep part muscle in skin damage district is normal simultaneously impaired, hardens atrophy and cause joint, the maimed work capacity that influences of limbs.

1.3 pathological change

44 examples in 84 examples have been done skin biopsy, pathological change is significant, its intradermal collagen fiber swelling, fusion, homogenizing, it is identical with systemic sclerosis I type person to change, but some different characteristics are arranged also, (1) epidermis has keratinization phenomenon (32 example) in various degree, the epithelial layer atrophy is not obvious have thicken (10 example) on the contrary; (2) pin cortex elastic fibers changes obviously, and shallow-layer is arranged fine and close (17/24 example) and swelling, thick, fracture, and deep layer is then arranged inequality, has to lack in the form of sheets as the person; (3) cell infiltration more and significantly (18/44 example).

2 treatment and curative effects

2.1 Therapeutic Method

This group adopts oral vascular tablet for recovery, every day three times, each 8.

Treatment time is not wait to 3 years 10 months in one month, and average course of treatment is 9 months, and wherein the half a year course of treatment, 7 months to 1 year with interior person's 23 examples with interior person's 40 examples.

This is organized 84 routine patients big portion before coming institute and once used adrenocortical hormone, testosterone propionate, bismuth salicylate, penicillin etc., does not all obtain curative effect, when coming institute to accept then stop using-to cut medicine for treatment previously after this law treatment.

2.2 criterion of therapeutical effect

Clinical cure: skin lesion all disappears, and color and luster, elasticity, pliability are all near normal skin, and it is normal that appendages recovers, joint function recovery (lopsided person's exception has taken place).Or skin biopsy before and after the treatment, pathological changes is recovered normal person.

Produce effects: the most of deliquescing of skin lesion, the sclerosis area dwindles, and the skin lesion of atrophy obviously protuberance is plentiful, and pigment anomaly is clearly better, and the function of skin appendages is improved.Sick in a word decrease recover 50% with--go up the person.

Effectively: the skin sclerosis deliquescing, ischemic tissue is more plentiful, and color and luster recovers gradually.

Invalid: treatment does not have progress person more than one month.

2.3 treatment performance

Treatment back skin turgor, sclerosis and atrophy all can recover.The take medicine skin and the subcutaneous fat deliquescing gradually of after-hardening, can returning to of having is normal; The plentiful gradually deliquescing of atrophoderma depression person also can recover normal.

It is alopecia, dysidria person, pigment variation person that skin appendages changes, and recovery is in various degree all arranged after the treatment.The joint at skin sclerosis position, muscle damage and dysfunction person is taken place, the treatment back is softening along with skin, and its joint function disturbance also has corresponding improvement in various degree, but the general difficult degree that reaches remarkable improvement.(table 2)

2.4 efficacy evaluation

This is organized whole cases and evaluates by criterion of therapeutical effect, all demonstration in various degree curative effect, clinical cure person 4 examples, produce effects person's 36 examples, responder's 44 examples in 84 examples.(table 3)

The various local scleroderma skin lesion of table 2 recovery situation statistical table

Project		The speckle type	Ribbon type	The sword cut type	Multiple types	Amount to
							Skin sclerosis	Impaired number	??22	??25	??21	??8	??76
Recover normal	??1	??1	??1	??0	??3
						Significantly take a turn for the better		??14	??14	??14	??6	??48
Take a turn for the better	??7	??10	??6	??2	??25
						Do not have progressive		??0	??0	??0	??0	??0
Atrophoderma	Impaired number	??9	??8	??18	??2								??37
						Recover normal	??2	??0	??2	??0	??4
	Significantly take a turn for the better	??0	??0	??1	??0							??1
						Take a turn for the better	??7	??8	??15	??2	??32
	Do not have progressive	??0	??0	??0	??0							??0
						Pigment alteration	Impaired number	??16	??24	??22	??6		??68
Recover normal	??4	??2	??1	??0	??7
							Significantly take a turn for the better	??1	??3	??3	??1	??8
Take a turn for the better	??10	??19	??17	??5	??51
							Do not have progressive	??1	??0	??1	??0	??2
Alopecia	Impaired number	??4	??2	??16	??2								??24
						Recover normal	??3	??0	??1	??0	??4
	Significantly take a turn for the better	??0	??0	??0	??0							??0
						Take a turn for the better	??1	??2	??15	??2	??20
	Do not have progressive	??0	??0	??0	??0							??0
						Dysidria	Impaired number	??1	??3	??0	??2		??6
Recover normal	??0	??0	??0	??0	??0
							Significantly take a turn for the better	??0	??0	??0	??0	??0
Take a turn for the better	??0	??2	??0	??2	??4
							Do not have progressive	??1	??1	??0	??0	??2
The joint motion barrier	Impaired number	??0	??6	??0	??4								??10
						Recover normal	??0	??0	??0	??0	??0
	Significantly take a turn for the better	??0	??0	??0	??0							??0
						Take a turn for the better	??0	??6	??0	??3	??9

Hinder

Do not have progressive

????0

????0

????0

????1

????1

Table 3 vascular tablet for recovery treatment local scleroderma curative effect statistics

Project	Speckle type (23 example)	Ribbon type (26 example)	Sword cut type (27 example)	Multiple types (8 example)	Amount to (84 example)
						Clinical cure	??1	??2	??1	??0	??4(4.8％)
Produce effects	??11	??11	??10	??4	??36(42.9％)
						Effectively	??11	??13	??16	??4	??44(52.3％)

2.4 typical medical record for example

Temperature XX, male, 35 years old, soldier.

The conscious left upper arm outside sclerosis of the skin of patient, pain, skin lesion enlarge gradually, far reach back, left side, omoplate, oxter, left forearm, the back of the hand and the third finger.Once use treatments such as sodium calcium edetate, penicillin, ovocaine, Chinese medicine, physical therapy, but all failed disease controlling development.

Hard as the leather of left upper arm skin is cured sample gloss during prescription on individual diagnosis, is difficult for pinching.Left forearm, omoplate, locate the skin turgor sclerosis in the back of the body etc., a left side 4,5 refers to that skins are fixed in phalanges and can not move.Skin lesion district skin is filbert, oligotrichosis for fine hair on birds or animals, lossless drying.The left upper extremity function of joint is limited, can not go up act, and the range of activity of two wrists is obviously dwindled.The skin biopsy pathological diagnosis accords with the local scleroderma dermatosis, the swelling of intradermal collagen fiber, fusion chap, and the homogenizing sample becomes.

Begin to take " vascular tablet for recovery " week after being admitted to hospital, the remarkable deliquescing of skin lesion after three months is treated in the back one all skin deliquescing gradually of taking medicine, but the skin pinching.Treat the whole deliquescing of skin lesion after a year nine months, venae subcutaneae all swells surface, fine hair on birds or animals hair well-grown, cured sample gloss is eliminated, only residual have a more shallow pigment patch that is dispersed in, and joint function recovery is normal, nearby carries out the biopsy check once more in former bark fetching district, corium plantation fibre bundle becomes fiber, and it is normal that the skin histology form is recovered fully.

3 discuss

Local scleroderma does not still have effective therapy at present both at home and abroad, and according to the sclerodermatous experience of my institute's therapy system, the various local scleroderma that application vascular tablet for recovery has been treated one group of 84 example has obtained sure curative effect.

This group case is being come before the institute treatment, once passes through the therapy of various Chinese and western medicines institute outside and does not obtain curative effect; This group is used during the treatment of vascular tablet for recovery, stops to use all other Chinese and western drugses again; All skin lesion performance such as the skin sclerosis of cases, atrophy, pigment alteration, alopecia, dysidria and joint function disturbance all have in various degree improvement after the medication.More than can affirm fully the effectiveness of vascular tablet for recovery medicine, and can get rid of the probability of local scleroderma spontaneous remission.The case that wherein has is through the check of histopathology, proves that clearly the hardened phenomenon of glue unit recovers normally fully, and this has provided powerful support for the effectiveness of this therapy with regard to again from the change of pathomorphology.

4 conclusion

This group is used various local scleroderma 84 row of activating blood and removing stasis drug vascular tablet for recovery orally taken for curing, and wherein clinical cure 4 examples account for 4.8%, produce effects 36 examples, accounts for 42.9%, effective 44 examples, accounts for 52.3%, has obtained sure therapeutic effect.The form that puffing takes place after treatment hardened collagen fiber changes, and the pathological changes that collagen fiber is described is reversible, and is because the result of activating blood and removing stasis drug vascular tablet for recovery effect certainly.

The specific embodiment

Embodiment 1 preparation tablet

Take by weighing raw material by following weight proportion

Radix Salviae Miltiorrhizae 263.12g Caulis Spatholobi 263.12g Radix Curcumae 105.25g

Olibanum 42.10g Myrrha 42.10g

Preparation method

Olibanum, Myrrha, turmeric powder are broken into fine powder, and Radix Salviae Miltiorrhizae, Caulis Spatholobi are used water extraction three times, 1.5 hours for the first time, second and third time 1 hour extracted water temperature 98-102 ℃ at every turn, and extracting solution filters, merging filtrate is evaporated to the thick paste of relative density 1.35-1.40 (60 ± 5 ℃ heat survey); Thick paste adds Olibanum, Myrrha, Radix Curcumae fine powder, and mixing is made bulky grain, vacuum drying, and dry substance is ground into fine powder, and mixing is granulated, and tabletting is made 1000 (every 0.30g contains crude drug 0.72g), coating, promptly.Usage and dosage, oral, one time 8,3 times on the one; Menstrual period decrement, anemia of pregnant woman and lunger follow the doctor's advice and take.

Embodiment 2 preparation capsules

Take by weighing raw material by following weight proportion

Radix Salviae Miltiorrhizae 210.50g Caulis Spatholobi 210.50g Radix Curcumae 52.62g

Olibanum 21.05g Myrrha 21.05g

Preparation method

Olibanum, Myrrha, turmeric powder are broken into fine powder, and Radix Salviae Miltiorrhizae, Caulis Spatholobi are used water extraction three times, 1.5 hours for the first time, second and third time 1 hour extracted water temperature 98-102 ℃ at every turn, and extracting solution filters, merging filtrate is evaporated to the thick paste of relative density 1.35-1.40 (60 ± 5 ℃ heat survey); Thick paste adds Olibanum, Myrrha, Radix Curcumae fine powder, and mixing is made bulky grain, vacuum drying, and dry substance is ground into fine powder, and mixing is granulated, and is encapsulated, makes 537 (every 0.40g contains crude drug 0.96g), promptly.Usage and dosage, oral, one time 6,3 times on the one; Menstrual period decrement, anemia of pregnant woman and lunger follow the doctor's advice and take.

Claims (5)

1, a kind of treatment vasculitis, scleroderma and arteriosclerosis lower extremities vascular occlusion disease drug is characterized in that it being the medicament of being made by following materials of weight proportions

Radix Salviae Miltiorrhizae 20-30 part Caulis Spatholobi 20-30 part Radix Curcumae 5-15 part

Olibanum 2-6 part Myrrha 2-6 part

2, according to the described treatment vasculitis of claim 1, scleroderma and arteriosclerosis lower extremities vascular occlusion disease drug, wherein each raw material optimum weight proportioning is:

10 parts of 25 portions of Radix Curcumaes of 25 portions of Caulis Spatholobis of Radix Salviae Miltiorrhizae

4 parts of 4 parts of Myrrhas of Olibanum

3,, it is characterized in that said medicament is a said dosage form on any pharmaceutics according to the described treatment vasculitis of claim 1, scleroderma and arteriosclerosis lower extremities vascular occlusion disease drug.

4,, it is characterized in that said medicament is tablet, capsule according to the described treatment vasculitis of claim 3, scleroderma and arteriosclerosis lower extremities vascular occlusion disease drug.

5, according to the described treatment vasculitis of claim 1, scleroderma and arteriosclerosis lower extremities vascular occlusion disease drug, its preparation method is: Olibanum, Myrrha, turmeric powder are broken into fine powder, Radix Salviae Miltiorrhizae, Caulis Spatholobi are used water extraction three times, 1.5 hours for the first time, second and third time 1 hour extracted water temperature 98-102 ℃ at every turn, and extracting solution filters, merging filtrate is evaporated to the thick paste of relative density 1.35-1.40 (60 ± 5 ℃ heat survey); Thick paste adds Olibanum, Myrrha, Radix Curcumae fine powder, and mixing is made bulky grain, vacuum drying, and dry substance is ground into fine powder, and mixing is made said dosage form on any pharmaceutics.