CN1628827A - Pharmaceutical composition for treating lumbago due to kidney-asthenia and its preparing process - Google Patents
Pharmaceutical composition for treating lumbago due to kidney-asthenia and its preparing process Download PDFInfo
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- CN1628827A CN1628827A CN 200410073855 CN200410073855A CN1628827A CN 1628827 A CN1628827 A CN 1628827A CN 200410073855 CN200410073855 CN 200410073855 CN 200410073855 A CN200410073855 A CN 200410073855A CN 1628827 A CN1628827 A CN 1628827A
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Abstract
Disclosed is a medicinal composition for treating deficiency of the kidney, which is mainly prepared from Chinese medicinal herbs including broomrape, common fennel fruit, prepared rehmannia root, psoralea fruit, epimeddium, cnidium fruit, achyranthes and cyathula root, dipsacus root, licorice root, eucommia bark, dodder seed, wolferry fruit, plantain seeds, common fennel fruit, prepared aconite root, schisandra fruit, frankincense, myrrh, clove, cynomorium songaricum, camphor, boneol, peppermint oil, Cinnamomum cassia oil, and methyl ester salicylate.
Description
Technical field
The present invention relates to a kind of new pharmaceutical composition that is used for the treatment of lumbago due to renal deficiency, relate in particular to a kind of main with the Chinese herbal medicine be raw material make be used for the treatment of pharmaceutical composition of lumbago due to renal deficiency and preparation method thereof.
Background technology
Lumbago is a kind of commonly encountered diseases, frequently-occurring disease.Theory of Chinese medical science thinks that the inducement of lumbago is a lot of, wind, wet, cold, heat arranged, vexedly frustrates, congestion, the stagnation of QI, the stasis of blood is long-pending, but all be mark, and be it and suffer from a deficiency of the kidney.Waist is the internal organs of kidney, and the kidney governing bones marrow.Deficiency of kidney-essence, bone marrow does not fill, so the soft lower limb knee joint of the soreness of waist is unable.Yang deficiency can not the replenishing vital QI with drugs of warm nature extremity, so hands and feet being not warm is arranged, pale white complexion waits disease." element ask arteries and veins want precise and tiny opinion " said: " the waist person, the internal organs of kidney, incapable of turning round, kidney is with exhausted." illustrate that the relation of lumbago and kidney is very close.
The medicine of the treatment lumbago of having gone on the market up to now mainly contains compound Nanxing pain paste, SHANGSHI ZHITONG GAO, pain-relieving plaster for injury and rheumatism, ZHUANGGU SHEXIANG ZHITONG GAO, pain is pasted spirit, it and ZHUIFENG GAO, pain-relieving plaster for arthritis, bone leads to plaster, about 178 kinds of similar kinds such as Moschus wind-damp dispelling cream, the contained main component of these medicines has: Radix Aconiti Kusnezoffii, Radix Aconiti, Olibanum, Myrrha, Semen Strychni, Cortex Cinnamomi, methyl salicylate, Mentholum, Borneolum Syntheticum, Camphora, Folium Symplocoris Caudatae, Semen daturae fluid extract, Os pardi, Moschus, Herba Ephedrae, Herba Asari, Rhizoma Et Radix Notopterygii, Radix Angelicae Pubescentis, Radix Clematidis, Flos Carthami, Guangxi Sanguis Draxonis, Oleum Cinnamomi, Fructus Capsici fluidextract, iodine, potassium iodide, diphhydramine hydrochloride, Arisaema Cum Bile, Flos Caryophylli, the Radix Angelicae Dahuricae, Rhizoma Chuanxiong, Radix Cynanchi Paniculati, Radix Aconiti Brachypodi (Radix Aconiti Szechenyiani), Rhizoma Atractylodis, Rhizoma Zingiberis, Radix Angelicae Sinensis, Rhizoma Kaempferiae, Fructus Anisi Stellati, Radix Stephaniae Sinicae (Radix Stephaniae Dielsianae), Caulis Erycibes etc., these drug mains will be used for the treatment of traumatic injury, rheumatism, the lumbago that wind and cold causes, almost do not have and relate to the renal deficiency type lumbago, in addition they all in various degree exist the defective of taking stopgap measures and can not effect a permanent cure.
Summary of the invention
The object of the invention provides a kind of the kidney invigorating with the inside and outside medication, reaches the pharmaceutical composition of radical cure lumbago by the kidney invigorating.
Another object of the present invention provides a kind of this preparation of drug combination method.
The present invention seeks to realize by following technological approaches:
A kind of pharmaceutical composition for the treatment of lumbago is characterized in that mainly being made up of following raw medicaments in portion by weight:
9～87 parts of 9～87 parts of Radix Rehmanniae Preparata of 9～87 parts of Fructus Anisi Stellatis of Herba Cistanches
9～87 parts of 9～87 parts of Fructus Cnidiis of 9～87 parts of Herba Epimedii of Fructus Psoraleae
9～87 parts in 9～87 portions of Radix Glycyrrhizaes of 9～87 parts of Radix Dipsacis of Radix Achyranthis Bidentatae
9～87 parts of 9～87 parts of Fructus Lycii of 9～87 parts of Semen Cuscutae of the Cortex Eucommiae
6～57 parts of 9～87 parts of Radix Aconiti Lateralis Preparatas of 9～87 parts of Fructus Foeniculi of Semen Plantaginis
6～57 parts of 3～30 parts of Myrrhas of 6～57 parts of Olibanums of Fructus Schisandrae Chinensis
6～60 parts of 1～13 part of Camphoras of 6～57 parts of Herba Cynomoriis of Flos Caryophylli
1～11 part of 5～50 parts of Oleum Cinnamomi of 4～39 portions of Oleum menthae of Borneolum Syntheticum
11～103 parts of 11～99 parts of Resina Liquidambaris thick pastes of methyl salicylate
The weight portion ratio range of each component of pharmaceutical composition of the present invention is:
14～58 parts of 14～58 parts of Radix Rehmanniae Preparata of 14～58 parts of Fructus Anisi Stellatis of Herba Cistanches
14～58 parts of 14～58 parts of Fructus Cnidiis of 14～58 parts of Herba Epimedii of Fructus Psoraleae
14～58 parts in 14～58 portions of Radix Glycyrrhizaes of 14～58 parts of Radix Dipsacis of Radix Achyranthis Bidentatae
14～58 parts of 14～58 parts of Fructus Lycii of 14～58 parts of Semen Cuscutae of the Cortex Eucommiae
9～38 parts of 14～58 parts of Radix Aconiti Lateralis Preparatas of 14～58 parts of Fructus Foeniculi of Semen Plantaginis
5～20 parts of 5～20 parts of Myrrhas of 9～38 parts of Olibanums of Fructus Schisandrae Chinensis
10～40 parts of 2～9 parts of Camphoras of 5～20 parts of Herba Cynomoriis of Flos Caryophylli
1～7 part of 8～33 parts of Oleum Cinnamomi of 6～20 portions of Oleum menthae of Borneolum Syntheticum
17～69 parts of 16～66 parts of Resina Liquidambaris thick pastes of methyl salicylate
The parts by weight of each component of pharmaceutical composition of the present invention are:
30 parts of 30 parts of Radix Rehmanniae Preparata of 30 parts of Fructus Anisi Stellatis of Herba Cistanches
30 parts of 30 parts of Fructus Cnidiis of 30 parts of Herba Epimedii of Fructus Psoraleae
30 parts in 30 portions of Radix Glycyrrhizaes of 30 parts of Radix Dipsacis of Radix Achyranthis Bidentatae
30 parts of 30 parts of Fructus Lycii of 30 parts of Semen Cuscutae of the Cortex Eucommiae
20 parts of 30 parts of Radix Aconiti Lateralis Preparatas of 30 parts of Fructus Foeniculi of Semen Plantaginis
10 parts of 10 parts of Myrrhas of 20 parts of Olibanums of Fructus Schisandrae Chinensis
21 parts of 5 parts of Camphoras of 10 parts of Herba Cynomoriis of Flos Caryophylli
4 parts of 18 parts of Oleum Cinnamomi of 14 portions of Oleum menthae of Borneolum Syntheticum
36 parts of 34 parts of Resina Liquidambaris thick pastes of methyl salicylate
Pharmaceutical composition of the present invention also can add the diphhydramine hydrochloride of 2～23 weight portions.
Pharmaceutical composition of the present invention can be made up of following bulk drugs:
9～87 parts of 9～87 parts of Radix Rehmanniae Preparata of 9～87 parts of Fructus Anisi Stellatis of Herba Cistanches
9～87 parts of 9～87 parts of Fructus Cnidiis of 9～87 parts of Herba Epimedii of Fructus Psoraleae
9～87 parts in 9～87 portions of Radix Glycyrrhizaes of 9～87 parts of Radix Dipsacis of Radix Achyranthis Bidentatae
9～87 parts of 9～87 parts of Fructus Lycii of 9～87 parts of Semen Cuscutae of the Cortex Eucommiae
6～57 parts of 9～87 parts of Radix Aconiti Lateralis Preparatas of 9～87 parts of Fructus Foeniculi of Semen Plantaginis
6～57 parts of 3～30 parts of Myrrhas of 6～57 parts of Olibanums of Fructus Schisandrae Chinensis
6～60 parts of 1～13 part of Camphoras of 6～57 parts of Herba Cynomoriis of Flos Caryophylli
1～11 part of 5～50 parts of Oleum Cinnamomi of 4～39 portions of Oleum menthae of Borneolum Syntheticum
2～23 parts of 11～103 parts of diphhydramine hydrochlorides of 11～99 parts of Resina Liquidambaris thick pastes of methyl salicylate
Be preferably:
14～58 parts of 14～58 parts of Radix Rehmanniae Preparata of 14～58 parts of Fructus Anisi Stellatis of Herba Cistanches
14～58 parts of 14～58 parts of Fructus Cnidiis of 14～58 parts of Herba Epimedii of Fructus Psoraleae
14～58 parts in 14～58 portions of Radix Glycyrrhizaes of 14～58 parts of Radix Dipsacis of Radix Achyranthis Bidentatae
14～58 parts of 14～58 parts of Fructus Lycii of 14～58 parts of Semen Cuscutae of the Cortex Eucommiae
9～38 parts of 14～58 parts of Radix Aconiti Lateralis Preparatas of 14～58 parts of Fructus Foeniculi of Semen Plantaginis
5～20 parts of 5～20 parts of Myrrhas of 9～38 parts of Olibanums of Fructus Schisandrae Chinensis
10～40 parts of 2～9 parts of Camphoras of 5～20 parts of Herba Cynomoriis of Flos Caryophylli
1～7 part of 8～33 parts of Oleum Cinnamomi of 6～20 portions of Oleum menthae of Borneolum Syntheticum
3～15 parts of 17～69 parts of diphhydramine hydrochlorides of 16～66 parts of Resina Liquidambaris thick pastes of methyl salicylate
More preferably:
30 parts of 30 parts of Radix Rehmanniae Preparata of 30 parts of Fructus Anisi Stellatis of Herba Cistanches
30 parts of 30 parts of Fructus Cnidiis of 30 parts of Herba Epimedii of Fructus Psoraleae
30 parts in 30 portions of Radix Glycyrrhizaes of 30 parts of Radix Dipsacis of Radix Achyranthis Bidentatae
30 parts of 30 parts of Fructus Lycii of 30 parts of Semen Cuscutae of the Cortex Eucommiae
20 parts of 30 parts of Radix Aconiti Lateralis Preparatas of 30 parts of Fructus Foeniculi of Semen Plantaginis
10 parts of 10 parts of Myrrhas of 20 parts of Olibanums of Fructus Schisandrae Chinensis
21 parts of 5 parts of Camphoras of 10 parts of Herba Cynomoriis of Flos Caryophylli
4 parts of 18 parts of Oleum Cinnamomi of 14 portions of Oleum menthae of Borneolum Syntheticum
8 parts of 36 parts of diphhydramine hydrochlorides of 34 parts of Resina Liquidambaris thick pastes of methyl salicylate
The present invention treats a kind of preparation method of the pharmaceutical composition of lumbago due to renal deficiency, may further comprise the steps:
(1) take by weighing each component by following weight portion:
9～87 parts of 9～87 parts of Radix Rehmanniae Preparata of 9～87 parts of Fructus Anisi Stellatis of Herba Cistanches
9～87 parts of 9～87 parts of Fructus Cnidiis of 9～87 parts of Herba Epimedii of Fructus Psoraleae
9～87 parts in 9～87 portions of Radix Glycyrrhizaes of 9～87 parts of Radix Dipsacis of Radix Achyranthis Bidentatae
9～87 parts of 9～87 parts of Fructus Lycii of 9～87 parts of Semen Cuscutae of the Cortex Eucommiae
6～57 parts of 9～87 parts of Radix Aconiti Lateralis Preparatas of 9～87 parts of Fructus Foeniculi of Semen Plantaginis
6～57 parts of 3～30 parts of Myrrhas of 6～57 parts of Olibanums of Fructus Schisandrae Chinensis
6～60 parts of 1～13 part of Camphoras of 6～57 parts of Herba Cynomoriis of Flos Caryophylli
1～11 part of 5～50 parts of Oleum Cinnamomi of 4～39 portions of Oleum menthae of Borneolum Syntheticum
11～103 parts of 11～99 parts of Resina Liquidambaris thick pastes of methyl salicylate
(2) volatile oil of extraction Flos Caryophylli and Fructus Anisi Stellati is standby; Fructus Anisi Stellati and Flos Caryophylli medicinal residues behind the extraction volatile oil are mixed with Herba Cistanches, Radix Rehmanniae Preparata, Fructus Psoraleae, Herba Epimedii, Fructus Cnidii, Radix Achyranthis Bidentatae, Radix Dipsaci, Radix Glycyrrhizae, the Cortex Eucommiae, Semen Cuscutae, Fructus Lycii, Semen Plantaginis, Fructus Foeniculi, Radix Aconiti Lateralis Preparata, Fructus Schisandrae Chinensis, Olibanum, Myrrha, Herba Cynomorii, added alcohol reflux 2 hours, extracting solution filters, reclaim ethanol, be condensed into thick paste.
(3) after the volatile oil that Camphora, Borneolum Syntheticum, Oleum menthae, Oleum Cinnamomi, methyl salicylate and step (2) are extracted is mixed together, mix with the prepared thick paste of Resina Liquidambaris thick paste and step (2) again, make the preparation intermediate, make preparation through preparations shaping technology again, promptly.
If add the diphhydramine hydrochloride of 2～23 weight portions, only need change (3) step of above-mentioned preparation method into following method and can make pharmaceutical composition of the present invention:
After the volatile oil that Camphora, Borneolum Syntheticum, Oleum menthae, Oleum Cinnamomi, methyl salicylate and step (2) are extracted is mixed together, mix with the prepared thick paste of Resina Liquidambaris thick paste, diphhydramine hydrochloride and step (2) again, make the preparation intermediate, make preparation through preparations shaping technology again, promptly.
The present composition based on Chinese medicine to pathogenetic research of lumbago deep layer and Therapeutic Principle thereof, simultaneously according to the pharmaceutical research achievement, filter out the crude drug of kidney invigorating and YANG supporting, promoting blood circulation to remove blood stasis, dispelling, collateral-activating,, be prepared from according to certain weight proportion according to the theory of Chinese medical science prescription.
The compatibility of pharmaceutical composition of the present invention is according to being:
Adopt the kidney invigorating such as Herba Cistanches, Herba Cynomorii, Herba Epimedii, Semen Cuscutae, Radix Rehmanniae Preparata, Fructus Lycii, Fructus Cnidii, Fructus Psoraleae, tonifying YANG, benefit essence; Be added with the Cortex Eucommiae, Radix Achyranthis Bidentatae, Radix Dipsaci, bone and muscle strengthening, dispelling, collateral-activating is to control soreness of waist and knee joint, the nocturia frequency.Insufficiency of kidney-YANG, hands and feet being not warm then, the extremity arthralgia pain is controlled the suitable big heat of Da Xin, Radix Aconiti Lateralis Preparata, Oleum Cinnamomi, Fructus Foeniculi, the hot warm tonifying YANG of Fructus Anisi Stellati; Olibanum, Myrrha promoting blood circulation to remove blood stasis; The Flos Caryophylli warming middle-JIAO to relieve pain, compatibility uses, and then yang-energy is sufficient, and it is wet to dispel cold, and warm brothers cease all pains.Methyl salicylate, Oleum menthae, Borneolum Syntheticum, Camphora etc. are refrigerant, antiinflammatory and said medicine match, and muscular soreness, Fengshi Guanjie pain curative effect are more brought out the best in each other.
Pharmaceutical composition of the present invention can be prepared into any acceptable clinically suitable formulations by this area conventional method, for example can be tablet, capsule, granule, powder, pill, oral liquid, syrup, drop pill, ointment, nasal formulations (comprising nasal drop), aerosol or spray, plaster, emplastrum (comprising rubber-emplastrum, cataplasma, patch), be preferably emplastrum (comprising rubber-emplastrum, cataplasma, patch).
The effective dose of pharmaceutical composition of the present invention is to use 2.4g～3.6g crude drug every day.
Pharmaceutical composition decapacitation of the present invention is effectively treated outside the lumbago that causes because of suffering from a deficiency of the kidney, and still can significantly improve symptoms such as the urgent micturition, frequent micturition and the seminal emission that cause because of suffering from a deficiency of the kidney, premature ejaculation, sexual impotence.
Further describe the present invention by the following examples, it should be understood that these embodiment only are used for the purpose of illustration, never limit the scope of the invention.
The specific embodiment
The preparation of [embodiment 1] emplastrum
(1) arrangement of medical material
Herba Cistanches: choose decontamination.
Each medicine such as Fructus Anisi Stellati, Radix Rehmanniae Preparata, Radix Aconiti Lateralis Preparata, Fructus Lycii, Semen Plantaginis, Fructus Foeniculi, Flos Caryophylli: choose decontamination.
Fructus Psoraleae, Fructus Cnidii, Fructus Schisandrae Chinensis: choose decontamination.
Herba Epimedii, Radix Glycyrrhizae: choose decontamination, cutting.
Radix Dipsaci, Herba Cynomorii: choose decontamination, cutting, lamellar.
Radix Achyranthis Bidentatae: choose decontamination.
The Cortex Eucommiae: choose decontamination.
Olibanum, Myrrha: choose decontamination.
Semen Cuscutae: choose decontamination.
(2) extraction of Fructus Anisi Stellati, Flos Caryophylli volatile oil
It is standby that 100g Flos Caryophylli, 300g Fructus Anisi Stellati are extracted volatile oil with the steam distillation method respectively.
(3) extraction of waist kidney thick paste
With Herba Cistanches 300g, Radix Rehmanniae Preparata 300g, Fructus Psoraleae 300g, Herba Epimedii 300g, Fructus Cnidii 300g, Radix Achyranthis Bidentatae 300g, Radix Dipsaci 300g, Radix Glycyrrhizae 300g, Cortex Eucommiae 300g, Semen Cuscutae 300g, Fructus Lycii 300g, Semen Plantaginis 300g, Fructus Foeniculi 300g, Radix Aconiti Lateralis Preparata 200g, Fructus Schisandrae Chinensis 200g, Olibanum 100g, Myrrha 100g, Herba Cynomorii 50g Flos Caryophylli, Fructus Anisi Stellati medicinal residues with step (2) gained, add ethanol, reflux, extract,, extracting solution are condensed into waist kidney thick paste.
(4) preparation of Resina Liquidambaris thick paste
The Resina Liquidambaris heating and melting is made the 360g thick paste.
(5) preparation of coating cream group
The Fructus Anisi Stellati volatile oil that a is extracted step (2), Flos Caryophylli volatile oil mix with 200g Camphora, 130g Borneolum Syntheticum, 180g Oleum menthae, 40g Oleum Cinnamomi, 330g methyl salicylate, 30g liquid Paraffin, add rubber or modified rubber again, add again in Colophonium or the modified rosin after making it softening, standby.
(lithopone is emplastrum preparation filler commonly used to b with lithopone 420g, in order to increase cream group hardness), 80g diphhydramine hydrochloride, step (3) prepared waist kidney thick paste and 360g Resina Liquidambaris thick paste and the standby rubber mixing of a step gained, with suitable equipment make be smelt evenly fine and smooth, rubber-like coating cream group.
C is evenly coated in b step gained coating cream group on the satisfactory cloth in coating machine, is cut into the cream sheet again, promptly.Every cream sheet contains crude drug 1.2g.
The preparation of [embodiment 2] pill
(1) arrangement of medical material
Herba Cistanches: choose decontamination.
Each medicine such as Fructus Anisi Stellati, Radix Rehmanniae Preparata, Radix Aconiti Lateralis Preparata, Fructus Lycii, Semen Plantaginis, Fructus Foeniculi, Flos Caryophylli: choose decontamination.
Fructus Psoraleae, Fructus Cnidii, Fructus Schisandrae Chinensis: choose decontamination.
Herba Epimedii, Radix Glycyrrhizae: choose decontamination.
Radix Dipsaci, Herba Cynomorii: choose decontamination.
Radix Achyranthis Bidentatae: choose decontamination.
The Cortex Eucommiae: choose decontamination.
Olibanum, Myrrha: choose decontamination.
Semen Cuscutae: choose decontamination.
(2) preparation of fine powder
The 180g Fructus Cnidii, 180g Semen Plantaginis, 180g Fructus Foeniculi, 110g Fructus Schisandrae Chinensis, 180g Herba Epimedii, 180g Radix Glycyrrhizae, 20g Herba Cynomorii, the 180g Semen Cuscutae that round after the reason are ground into fine powder with pulverizer, cross 100 mesh sieves, waist kidney fine powder.
(3) preparation of volatile oil
Get the 500g Flos Caryophylli, the 870g Fructus Anisi Stellati is extracted volatile oil respectively, then volatile oil is mixed with Camphora 180g, Borneolum Syntheticum 120g, Oleum menthae 150g, Oleum Cinnamomi 30g, methyl salicylate 330g, stir.
(4) preparation of waist kidney thick paste
Herba Cistanches 870g, Radix Rehmanniae Preparata 870g, Fructus Psoraleae 870g, Radix Achyranthis Bidentatae 870g, Radix Dipsaci 870g, Cortex Eucommiae 870g, Fructus Lycii 870g, Radix Aconiti Lateralis Preparata 870g, Olibanum 300g, Myrrha 600g, Resina Liquidambaris 1030g and Flos Caryophylli, Fructus Anisi Stellati medicinal residues are mixed, add ethanol, reflux, extracting solution is condensed into waist kidney thick paste.
(5) preparation of waist kidney agglomerate powder
1000g waist kidney thick paste is mixed with waist kidney fine powder, stirred 1～2 minute, make soft material, the stand basin, thickness is no more than 3cm, and drying is 40 hours under 95 ℃ ± 5 ℃ conditions of usefulness heated-air circulation oven, gets waist kidney agglomerate.Waist kidney agglomerate is pulverized with pulverizer, crosses 100 mesh sieves.Fine powder mixed in mixer 18 minutes, got waist kidney agglomerate powder.
(6) preparation of refined honey
Get Mel with jacketed pan heated and boiled to 110 ℃, while hot with the filtration of 80 mesh sieves, promptly.
(7) general ball
Getting refined honey, to add ethanol even with 1: 3 mixed, a small amount of waist kidney agglomerate powder is put into cylinder, start the pill cylinder, begin spray and add refined honey-alcohol mixeding liquid in a small amount, constantly be stirred to and make fine powder be moistening graininess, add an amount of waist kidney agglomerate powder powder again, continuing to stir makes fine powder evenly overlay on the granule, spray adds refined honey-alcohol mixeding liquid and Sa Jia fine powder successively again, makes powder slowly add the tiny pill of great achievement with the method, crosses the sieve in 1mm aperture, getting the piller of 1mm aperture sieve puts in the pill cylinder, continue to spray to add refined honey-alcohol mixeding liquid and spread to add fine powder, cross the sieve in 2mm～2.5mm aperture, get the piller that sieves and make the ball kind.
Add the ball kind in the pill cylinder, start the pill cylinder, spray adds the mixed liquor of an amount of refined honey-ethanol (1: 3), adds an amount of fine powder again after stirring makes the piller moistening, is the piller of 3.0mm～3.5mm size with the general ball of the method to diameter, sieves; Get the piller that sieves and drop in the pill cylinder, start pellet processing machine, more successively constantly spray add an amount of refined honey-ethanol (1: 2) mixed liquor and spread and add fine powder, pill is strengthened gradually, be 4.5mm～5.0mm size to the piller diameter till.Take out, sieve, the wet ball of getting ball footpath 4.5～5.0mm range size carries out drying.
(8) drying
To wet ball stand dish, every disc thickness is about 3cm, 60 ℃ of dryings 2 hours, 70 ℃ of dryings 2 hours rise to 75 ℃ then and carry out drying, to moisture＜9.0%, the ball embryo.
(9) coating
Place the pill cylinder to roll every cylinder ball embryo, and spray into volatile oil, stir evenly, in cylinder, rolled about 10 minutes, take out, get coated pill with Sprayable.
The preparation of [embodiment 3] tablet
(1) arrangement of medical material
Herba Cistanches: choose decontamination.
Each medicine such as Fructus Anisi Stellati, Radix Rehmanniae Preparata, Radix Aconiti Lateralis Preparata, Fructus Lycii, Semen Plantaginis, Fructus Foeniculi, Flos Caryophylli is chosen decontamination.
Fructus Psoraleae, Fructus Cnidii, Fructus Schisandrae Chinensis: choose decontamination.
Herba Epimedii, Radix Glycyrrhizae: choose decontamination.
Radix Dipsaci, Herba Cynomorii: choose decontamination.
Radix Achyranthis Bidentatae: choose decontamination.
The Cortex Eucommiae: choose decontamination.
Olibanum, Myrrha: choose decontamination.
Semen Cuscutae: choose decontamination.
(2) extraction of Fructus Anisi Stellati, Flos Caryophylli volatile oil
Get the 60g Flos Caryophylli, the 100g Fructus Anisi Stellati is extracted volatile oil respectively with steam distillation.
(3) extraction of waist kidney thick paste
Herba Cistanches 120g, Radix Rehmanniae Preparata 120g, Fructus Psoraleae 120g, Herba Epimedii 120g, Fructus Cnidii 120g, Radix Achyranthis Bidentatae 120g, Radix Dipsaci 120g, Radix Glycyrrhizae 120g, Cortex Eucommiae 120g, Semen Cuscutae 120g, Fructus Lycii 120g, Semen Plantaginis 120g, Fructus Foeniculi 120g, Radix Aconiti Lateralis Preparata 60g, Fructus Schisandrae Chinensis 60g, Olibanum 30g, Myrrha 60g, Herba Cynomorii 15g and Flos Caryophylli, Fructus Anisi Stellati medicinal residues are mixed, add ethanol, reflux, extracting solution is condensed into waist kidney thick paste.
(4) preparation of Resina Liquidambaris thick paste
The Resina Liquidambaris heating and melting is become thick paste.
(5) waist kidney spray powder
The spray drying in spray dryer with waist kidney thick paste and 130g Resina Liquidambaris thick paste mixing makes waist kidney spray powder.
(6) with step 2) volatile oil that extracted, 60g Camphora, 60g Borneolum Syntheticum, 55g Oleum menthae, 12g Oleum Cinnamomi, 120g methyl salicylate adds in the waist kidney spray powder and makes granule, tabletting, the bag film-coat is promptly.
The preparation of [embodiment 4] granule
(1) arrangement of medical material
Herba Cistanches: choose decontamination.
Each medicine such as Fructus Anisi Stellati, Radix Rehmanniae Preparata, Radix Aconiti Lateralis Preparata, Fructus Lycii, Semen Plantaginis, Fructus Foeniculi, Flos Caryophylli is chosen decontamination.
Fructus Psoraleae, Fructus Cnidii, Fructus Schisandrae Chinensis: choose decontamination.
Herba Epimedii, Radix Glycyrrhizae: choose decontamination.
Radix Dipsaci, Herba Cynomorii: choose decontamination.
Radix Achyranthis Bidentatae: choose decontamination.
The Cortex Eucommiae: choose decontamination.
Olibanum, Myrrha: choose decontamination.
Semen Cuscutae: choose decontamination.
(2) extraction of Fructus Anisi Stellati, Flos Caryophylli volatile oil
Get the 100g Flos Caryophylli, the 300g Fructus Anisi Stellati is received volatile oil respectively.
(3) extraction of waist kidney thick paste
With Herba Cistanches 300g, Radix Rehmanniae Preparata 300g, Fructus Psoraleae 300g, Herba Epimedii 300g, Fructus Cnidii 300g, Radix Achyranthis Bidentatae 300g, Radix Dipsaci 300g, Radix Glycyrrhizae 300g, Cortex Eucommiae 300g, Semen Cuscutae 300g, Fructus Lycii 300g, Semen Plantaginis 300g, Fructus Foeniculi 300g, Radix Aconiti Lateralis Preparata 200g, Fructus Schisandrae Chinensis 200g, Olibanum 100g, Myrrha 100g, Herba Cynomorii 50g with Flos Caryophylli, Fructus Anisi Stellati medicinal residues, add ethanol, reflux, extracting solution is condensed into waist kidney thick paste.
(4) preparation of Resina Liquidambaris thick paste
The Resina Liquidambaris heating and melting is become the 360g thick paste.
(5) waist kidney spray powder
The spray drying in spray dryer with waist kidney thick paste and 360g Resina Liquidambaris thick paste mixing makes waist kidney spray powder.
(6) volatile oil that step (2) is extracted, 210g Camphora, 140g Borneolum Syntheticum, 180g Oleum menthae, 40g Oleum Cinnamomi, 340g methyl salicylate adding waist kidney spray powder are made granule, promptly.
The preparation of [embodiment 5] capsule
(1) arrangement of medical material
Herba Cistanches: choose decontamination.
Each medicine such as Fructus Anisi Stellati, Radix Rehmanniae Preparata, Radix Aconiti Lateralis Preparata, Fructus Lycii, Semen Plantaginis, Fructus Foeniculi, Flos Caryophylli is chosen decontamination.
Fructus Psoraleae, Fructus Cnidii, Fructus Schisandrae Chinensis: choose decontamination.
Herba Epimedii, Radix Glycyrrhizae: choose decontamination.
Radix Dipsaci, Herba Cynomorii: choose decontamination.
Radix Achyranthis Bidentatae: choose decontamination.
The Cortex Eucommiae: choose decontamination.
Olibanum, Myrrha: choose decontamination.
Semen Cuscutae: choose decontamination.
(2) extraction of Fructus Anisi Stellati, Flos Caryophylli volatile oil
Get Flos Caryophylli 100g, Fructus Anisi Stellati 300g extracts volatile oil respectively.
(3) extraction of waist kidney thick paste
Herba Cistanches 300g, Radix Rehmanniae Preparata 300g, Fructus Psoraleae 300g, Herba Epimedii 300g, Fructus Cnidii 300g, Radix Achyranthis Bidentatae 300g, Radix Dipsaci 300g, Radix Glycyrrhizae 300g, Cortex Eucommiae 300g, Semen Cuscutae 300g, Fructus Lycii 300g, Semen Plantaginis 300g, Fructus Foeniculi 300g, Radix Aconiti Lateralis Preparata 200g, Fructus Schisandrae Chinensis 200g, Olibanum 100g, Myrrha 100g, Herba Cynomorii 50g and Flos Caryophylli, Fructus Anisi Stellati medicinal residues are mixed, add ethanol, reflux, extracting solution is condensed into waist kidney thick paste.
(4) preparation of Resina Liquidambaris thick paste
The Resina Liquidambaris heating and melting is become the 360g thick paste.
(5) waist kidney spray powder
The spray drying in spray dryer with waist kidney thick paste and Resina Liquidambaris thick paste mixing makes waist kidney spray powder.
(6) volatile oil, 210g Camphora, 140g Borneolum Syntheticum, 180g Oleum menthae, 40g Oleum Cinnamomi, the 340g methyl salicylate that step (2) is extracted joins in the waist kidney spray powder, and it is encapsulated to make granule, promptly.
[test example 1] pharmaceutical composition of the present invention is to the effect of the model of suffering from a deficiency of the kidney
One, test material
1, for the reagent thing: the external plaster sheet that the embodiment of the invention is prepared; Dosage is provided with: the use amount of the adult of 70Kg pharmaceutical composition external plaster of the present invention sheet is that (area is 2 * 6.2 * 9.0cm in 2 subsides/skies
2), being converted into body weight by body surface area is that the mouse skin administration area of 20g is low dosage 0.4 * 0.7cm
2, middle dosage 1.2 * 0.7cm
2, high dose 1.2 * 2.1cm
2, its dosage is respectively 1,3,9 times of adult.Being converted into body weight by body surface area is that the rat skin administration area of 200g is low dosage 2.0 * 1.0cm
2, middle dosage 3.0 * 2.0cm
2, high dose 3.0 * 6.0cm
2, its dosage be respectively the adult, 3,9 times.
2, blank excipient, for not containing the plaster sheet of medicine, mouse skin administration area is 0.6 * 0.7cm
2, it is 3.0 * 6.0cm that rat skin gives blank excipient area
2
3, positive control drug: JINGUI SHENQI WAN, calculate by adult's every day oral 24 (4.5g), being converted into body weight by body surface area is that 200g rat oral gavage dosage is the 0.08g/200g body weight.Calculate by adult's every day oral 24 (4.5g), being converted into body weight by body surface area is that 20g mouse stomach dosage is the 0.001g/20g body weight.
4, laboratory animal: the healthy SD rat is provided the laboratory animal quality certification number: 99A032 by Guangdong Medical Lab Animal Center.NIH is a mice, and body weight 20 ± 2g is provided by Guangdong Medical Lab Animal Center, the laboratory animal quality certification number: 99A030.
5, experimental apparatus and medicine: the JL-C Physiological Experiment is used instrument more, and Jia Long instrument plant in Shanghai produces; Gland fat purine (Adenine) is produced by Fluka BioChemika.
Two, test method and result
1, to the castrated rats model experiment of suffering from a deficiency of the kidney
Selecting SD is rat, male, body weight 200 ± 20g, with the elbow shears each group guinea pig back hair is cut off, dip in depilatory (Containing Sulfur sodium 8g, starch 7g with cotton balls, sugar 4g, glycerol 5g, Borax 1g, add water 75ml), be coated with gently at guinea pig back, clean the depilation part with warm water after 3 minutes, dry with gauze, about 7 * 7 square centimeters, its depilation area accounts for about 25% of body surface area.Rested one day, and used the ether light anaesthesia, routine disinfection, excision both sides testis is divided at random for reagent thing low dose group, middle dosage group, high dose group, blank group and positive controls, totally 5 groups, every group of 10 rats.It is male not castrated rats that alternative is selected SD, 10, and as the normal control group.Each organizes rat by corresponding route of administration administration, and the route of administration of test group, blank group is a percutaneous drug delivery, and positive controls is an oral administration, successive administration 45 days.Every depilation in 15 days once.The 46th day, adopt Physiological Experiment how to be positioned over rat penis position with the stimulating electrode of instrument, award local electricity irritation, current intensity is 4mA, voltage is that the 40mV record begins to the penis erection time from stimulation.Put to death rat, dissect rat preputial glands, seminal fluid capsule, prostate and levator ani weigh, experimental result sees Table 1.
Table 1 pharmaceutical composition of the present invention to castrated rats suffer from a deficiency of the kidney model experiment (x ± SD, n=10)
| Group | Body weight (g) | The erection time (s) | Preputial glands index (mg/100g) | (seminal vesicle+prostate) index (mg/100g) | Levator ani index (mg/100g) |
| The normal control group | 324.5±29.5 | ?9.4±4.8* | 47.9±12.5*** | 508.0±77.7*** | ?34.2±5.6*** |
| The blank group | 298.5±32.1 | ?14.2±4.2 | 26.9±9.1 | 33.7±12.0 | ?13.1±3.7 |
| Low dose group | 294.7±32.5 | ?6.3±5.0*** | 28.2±6.0** | 32.8±6.7 | ?15.9±3.1*** |
| Middle dosage group | 295.8±19.6 | ?5.9±3.0*** | 34.2±12.9*** | 41.5±10.3 | ?15.1±2.7 |
| High dose group | 304.4±20.4 | ?8.0±5.2*** | 32.7±10.7*** | 49.4±19.1* | ?17.6±4.6 |
| Positive controls | 306.3±15.1 | ?3.7±2.3*** | 37.3±5.8*** | 100.4±12.6*** | ?23.4±3.9* |
Compare with the blank group,
P＞0.05, * P＜0.05, * * P＜0.01, * * * P＜0.001.
2, to the effect of gland fat purine induced mice renal function model of yang asthenia
Choose 50 of adult healthy mices, body weight 20 ± 2g is male entirely.5 dosage groups are set, are respectively for reagent thing low dose group, middle dosage group, high dose group, blank group and positive controls, every group of 10 mices.Route of administration: each group mouse back hair is cut off with the elbow shears, dip in depilatory (Containing Sulfur sodium 8g, starch 7g, sugared 4g with cotton balls, glycerol 5g, Borax 1g adds water 75ml), be coated with gently at mouse back, clean the depilation part with warm water after 3 minutes, dry with gauze, rested one day, press the dosage percutaneous drug delivery.Blank group is pasted with blank excipient.Each is organized mice and feeds with gland fat purine (adenine) change feedstuff feed (content about about 0.6%) every day.Intake 200mg/kg every day body weight.Respectively organize simultaneously mice administration respectively.Every depilation in 10 days once.Selecting 10 mices else does not feed to contain gland fat purine feedstuff as the normal control group.After 30 days, mice is plucked eye and gets blood, measures blood urea nitrogen (BUN) and flesh liver (Cr) content, puts to death mice, its thymus of weighing and spleen weight, and result of the test sees Table 2.
Table 2 pharmaceutical composition of the present invention to the effect of gland fat purine induced mice renal function model of yang asthenia (x ± SD, n=10)
| Project | Body weight (g) before the administration | Body weight after the administration (g) | BUN (mMol/L) | Cr (mg/dl) | Thymus coefficient (* 10 -3) | Spleen coefficient (* 10 -3) |
| The normal control group | 20.67±1.17 | 30.51±2.75*** | 5.86±1.09*** | 1.13±0.33*** | 25.7±3.4*** | 38.3±4.0*** |
| The blank group | 20.44±1.24 | 24.2±1.67 | 10.52±2.10 | 1.82±0.37 | 11.5±2.0 | 30.4±5.3 |
| Low dose group | 20.86±0.96 | 25.82±1.30* | 8.64±1.73* | 1.62±0.33 | 12.3±2.1 | 33.6±6.7 |
| Middle dosage group | 21.21±1.56 | 27.14±2.23** | 7.03±1.64*** | 1.31±0.44* | 12.6±2.0 | 33.9±5.2 |
| High dose group | 20.30±1.39 | 28.62±1.60*** | 6.61±1.67*** | 1.06±0.29*** | 13.1±4.0 | 37.8±5.8** |
| Positive controls | 21.63±1.18 | 30.42±2.76*** | 7.37±1.04*** | 1.19±0.31*** | 13.3±2.3 | 37.1±5.6** |
Compare with the blank group,
P＞0.05, * P＜0.05, * * P＜0.01, * * * P＜0.001.
Result of the test: 1) suffer from a deficiency of the kidney the model experiment result as can be known by castrated rats, the incubation period that castrated rats is subjected to electricity irritation erection can effectively be shortened for the basic, normal, high dosage of reagent thing, improve preputial glands, (seminal vesicle+prostate) and levator ani index, compare with the blank group, have highly significant.
2) by gland fat purine induced mice renal function model of yang asthenia experimental result as can be known, compare with the normal control group, blank group mice weight loss, serum BUN, Cr content carrying out property occurs and increase, thymus and spleen atrophy, can slow down gland fat purine induced mice body weight for the reagent thing and reduce, reduce BUN, Cr content, prompting has the effect of kidney invigorating and YANG supporting for the reagent thing.
The skin acute toxicity test of [test example 2] pharmaceutical composition of the present invention
One, test material
1, for test agent: the external plaster sheet that the embodiment of the invention is prepared, it is standby to be cut into required area during experiment.
2, laboratory animal: the closed colony Cavia porcellus is provided quality certification book number by No.1 Military Medical Univ.'s Experimental Animal Center: Guangdong probatio inspectionem pecuoarem word 99A047 number.
Two, test method and result
Select 8 of healthy guinea pigs, body weight 260 ± 20g, male and female half and half cut off the guinea pig back hair with the elbow shears, dip in depilatory (Containing Sulfur sodium 8g, starch 7g, sugared 4g with cotton balls, glycerol 5g, Borax 1g adds water 75ml), be coated with gently at guinea pig back, clean the depilation part with warm water after 3 minutes, dry with gauze, about 7 * 7 square centimeters, its depilation area accounts for about 30% of body surface area, rests one day, per 4 one group, be divided into 2 groups, i.e. skin injury Cavia porcellus group and intact skin Cavia porcellus group.The skin injury Cavia porcellus is for slightly to scratch skin surface equably with aseptic syringe needle.
Surpass valid density more than 20 times for reagent agent amount, do not occur abnormal response yet, then only establish a dosage group.The plaster sheet that the embodiment of the invention is prepared is cut into required area (7 * 7cm
2), be attached to the skin of back surface of corresponding Cavia porcellus respectively, after 24 hours, be subjected to the medicine district to tear institute's rubberized fabric off.Observed dermoreaction in continuous 7 days, record death condition and whole body are poisoned apparent.
Three, dosage design
The use amount of adult's pharmaceutical composition of the present invention of 70Kg is that (every veneer is long-pending to be 6.2 * 9.0cm in 2 subsides/skies
2), being converted into average weight and being the area that the Cavia porcellus of 260g should paste is 2 * 6.2 * 9.0 * 260 ÷ (31.5 * 400)=2.3cm
221 times using dosage is 2.3 * 21=48.3cm
2, be equivalent to 7 * 7cm
2
Table 3 pharmaceutical composition of the present invention is to the research of guinea pig skin acute toxicity
| Female Cavia porcellus | Male guinea pig | |||||||
| Intact skin | Damaged skin | Intact skin | Damaged skin | |||||
| The 1st day | ????0 | ????0 | ????0 | ????0 | ????0 | ????0 | ????0 | ????0 |
| The 2nd day | ????0 | ????0 | ????0 | ????0 | ????0 | ????0 | ????0 | ????0 |
| The 3rd day | ????0 | ????0 | ????0 | ????0 | ????0 | ????0 | ????0 | ????0 |
| The 4th day | ????0 | ????0 | ????0 | ????0 | ????0 | ????0 | ????0 | ????0 |
| The 5th day | ????0 | ????0 | ????0 | ????0 | ????0 | ????0 | ????0 | ????0 |
| The 6th day | ????0 | ????0 | ????0 | ????0 | ????0 | ????0 | ????0 | ????0 |
| The 7th day | ????0 | ????0 | ????0 | ????0 | ????0 | ????0 | ????0 | ????0 |
Annotate: it is 1 that poisoning symptom is arranged, and no poisoning symptom is 0.
Result of the test; Under the situation of 21 times (the administration area has reached maximum) being equivalent to the per day for adults using dosage, damaged skin Cavia porcellus and intact skin Cavia porcellus all do not have poisoning and the phenomena of mortality occur, and illustrates that pharmaceutical composition of the present invention is nontoxic, safety medicine for the reagent thing.
[test example 3] long-term toxicologic study of pharmaceutical composition of the present invention
One, test material
1, for the reagent thing: the external plaster sheet that the embodiment of the invention is prepared
2, laboratory animal: the healthy SD rat, 80, each 40 of male and female, female body weight is 100 ± 20g, male body weight is 110 ± 20g, and the laboratory animal quality certification: 99A032 is provided by Guangdong Medical Lab Animal Center; Raise in the big mouse cage of rustless steel, male and female rat sub-cage rearing, 5 in every cage, Animal Lab. is the cleaning level, central air-conditioning is concentrated ventilation 8-15 time/hour, temperature 20-24 ℃, relative humidity 55-65%, natural lighting.Feed full nutrition pellet, drinking water packs into after filtering with water purifier for city tap-water freely drinks in the drinking-water bottle.
3, test reagent
Total protein test kit (biuret method): produce lot number: 991229 by Beijing Zhongsheng Biological Engineering High Technology Company;
Albumin reagent box (bromocresol green method): produce lot number 991221 by Beijing Zhongsheng Biological Engineering High Technology Company;
Aspartate amino transferase test kit (IFCC recommends method): produce lot number 000601 by Beijing Zhongsheng Biological Engineering High Technology Company;
Alanine aminotransferase test kit (IFCC recommends method): produce lot number: 000601 by Beijing Zhongsheng Biological Engineering High Technology Company;
Creatinine liquid reagent box: produce lot number: 000501 by Beijing Zhongsheng Biological Engineering High Technology Company;
Determination of urea nitrogen test kit: produce lot number: 000501 by Beijing Zhongsheng Biological Engineering High Technology Company;
Blood glucose liquid reagent box (GOD-PAP method): produce by Beijing Zhongsheng Biological Engineering High Technology Company,
Lot number: 000601;
Cholesterol reagent box (CHOD-PAP method): produce lot number: 000502 by Beijing Zhongsheng Biological Engineering High Technology Company;
Alkaline phosphatase enzyme reagent kit (AMP buffer): produce lot number: 000601 by Beijing Zhongsheng Biological Engineering High Technology Company;
Two, test method
1, dosage grouping
1) for the reagent thing: the plaster sheet that the embodiment of the invention is prepared
High dose group: 13 * 10cm
2/ 200g body weight (be equivalent to intend referrer's clinical dosage 65.0 times)
Middle dosage group: 6.5 * 10cm
2/ 200g body weight (be equivalent to intend referrer's clinical dosage 32.5 times)
Low dose group: 6.5 * 3cm
2/ 200g body weight (be equivalent to intend referrer's clinical dosage 10.0 times)
2) blank group: blank excipient 13 * 10cm
2/ 200g body weight
Above dosage is cut into paster and is affixed on rat back.
Dosage is provided with foundation: the prepared plaster sheet of the embodiment of the invention is 2 * 6.2cm * 9.0cm consumption Equivalent Conversion by 70kg adult's bonding area every day, and the prepared basic, normal, high dosage group of the plaster sheet rat dosage of the embodiment of the invention is equivalent to 65 times, 32.5 times, 10.0 times of adult's consumption respectively.
Route of administration: each group rat back hair is cut off with the elbow shears, dip in depilatory (Containing Sulfur sodium 8g with cotton balls, starch 7g, sugared 4g, glycerol 5g, Borax 1g, add water 75ml), be coated with gently at rat back, clean the depilation part with warm water after 3 minutes, dry with gauze, press dosage percutaneous drug delivery every day.Every 20 days, again once with the depilatory depilation.
2, test method
P.199, " rat long term toxicity test " method is carried out according to bureau of drug administration of Ministry of Health of the People's Republic of China " new drug (Western medicine) preclinical study guideline compilation ".Get 80 of the healthy SD rats of Pass Test requirement, each 40 of male and female are numbered by " discriminating of rat and numbering S0P/GT Z/084 ", male be odd number, female be even number.Be divided into four test group at random by body weight, promptly supply high, medium and low three the dosage groups of reagent thing and a blank group, 20 every group, male and female half and half.Observe a week before the test, and write down body weight and basic data such as the amount of drinking water of ingesting, answer there was no significant difference between each group.In the 60d continuously every day percutaneous drug delivery once, every morning the observed and recorded rat general signs (comprising behavioral activity, breathing, hair color, mouth, eye, ear, nose, excrement, urine etc.), food ration, amount of drinking water and death condition.Discovery has the animal of toxic reaction to take out single cage raising, primary part observation.Discovery has dead and the timely corpse of dying animal is picked up, and does gross examination of skeletal muscle and histopathologic examination.Every body weight of 7d weighing.Continuously to after being subjected to medicine 60d, each group is randomly drawed 10 of rats respectively, male and female half and half, and fasting be can't help water more than 12 hours before checking.Through plucking the eye blood sampling, measure erythrocyte (RBC), leukocyte (WBC), platelet (PLT), hemoglobin (HGB) and blood smear microscopy leukocyte differential count with cellanalyzer.Serum is with 752 type ultraviolet spectrophotometers and pairing kit measurement aspartate amino transferase (AST), alanine aminotransferase (ALT), alkali phosphatase (AKP), blood urea nitrogen (BUN), total protein (TP), albumin (ALB), blood glucose (GLU), creatinine (Crea) and T-CHOL (T-CHO).Take by weighing animal important organ-heart, brain, liver, spleen, lung, kidney, adrenal gland's (one-sided), uterus, prostate, ovary (one-sided), testis (one-sided) simultaneously, dissect check, calculate the percentage rate (internal organs index) of internal organs percentage of liveweight, be left respectively to organize rat behind drug withdrawal 15d, carry out the mensuration of hemogram and biochemical indicator, take by weighing animal important organ-heart, brain, liver, spleen, lung, kidney, adrenal gland's (one-sided), uterus, prostate, ovary (one-sided), testis (one-sided) simultaneously, carry out histology's microscopy and observe, calculate the internal organs index.
Internal organs index=internal organs weight ÷ the weight of animals
More than every observation index handle the overall merit result of the test with the NDST statistical software.
Illustrate:
The English full name Chinese that is called for short
PLT Platelet platelet
ALB Albumin albumin
ALT alanine aminotransferase alanine aminotransferase
AST aspartate aminotransferase aspartic transaminase
BUN blood urea nitrogen blood urea nitrogen
Crea Creatinine creatinine
TP total-protein gross protein
HGB Hemoglobin hemoglobin
RBC red blood cell erythrocyte
T-CHO Cholesterol cholesterol
WBC white blood cell leukocyte
GLU Glucose blood glucose
Three, result of the test
1, general symptom:
For three dosage of reagent thing group, rat is in entire test, and all any abnormal response and death appear in the end.
2, body weight change:
Supply each dosage group of reagent thing group and blank group in the 0th, 8,16,24,32,40, weighed in 48,56,64 days, the result shows that the body weight of rat increases along with the increase of time, but compares there was no significant difference (being P＞0.05) with the blank group for the average weight of reagent thing group rat. and ingesting of laboratory animal is all normal with amount of drinking water. and details see the following form shown in 4
The test group that table 4 rat skin is continuous to give medicine of the present invention in 60 days drug withdrawal measure in the time of 15 days the variation that S.D. is a rat body weight (x ± SD, n=10)
| For reagent thing low dose group male and female | For dosage group male and female in the reagent thing | For reagent object height dosage group male and female | Blank group male and female | |
| ??0d | ??103.1±9.8??????97.2±7.8 | ??103.9±9.5?????96.7±6.0 | ??111.4±7.5?????103.2±6.7 | ??101.7±6.7??????106.7±6.0 |
| ??8d | ??132.2±13.4?????130.5±14.3 | ??140.9±7.7?????131.2±9.9 | ??143.4±9.4?????137.7±15.3 | ??135.1±13.1?????131.3±10.8 |
| ??16d | ??159.6±10.8?????158.6±12.7 | ??166.3±7.4?????160.6±14.4 | ??162.0±11.2????167.8±20.5 | ??161.1±15.5?????159.3±14.6 |
| ??24d | ??177.8±11.2?????172.6±29.7 | ??177.5±6.3?????176.0±21.3 | ??176.6±13.5????177.4±28.5 | ??182.1±14.2?????188.0±13.9 |
| ??32d | ??189.9±12.4?????181.0±19.2 | ??190.8±10.0????184.7±14.4 | ??196.0±12.0????198.1±22.9 | ??188.9±17.4?????197.5±16.4 |
| ??40d | ??190.9±11.3?????190.6±20.1 | ??194.2±17.3????199.1±17.4 | ??191.3±16.1????208.5±21.1 | ??190.2±16.2?????206.2±17.5 |
| ??48d | ??193?9±12.6?????203.9±22.5 | ??195.0±10.9????207.9±14.8 | ??190.2±13.4????208.5±20.7 | ??193.3±23.0?????210.0±9.5 |
| ??56d | ??208.0±10.4?????205±18.6 | ??201.6±18.1????217±24.0 | ??211.9±14.4????214.0±22.98 | ??201.4±18.0?????218.4±14.5 |
| ??64d | ??212.2±15.1?????208.8±17.8 | ??216.4±21.9????216.2±24.8 | ??210.0±22.4????209.6±10.14 | ??196.8±19.5?????216.2±17.8 |
With the same period blank same sex matched group compare P＞0.05 (sign slightly);
3, hematological examination:
Supply basic, normal, high three dosed administrations of reagent thing 60 days, low dose group rat large mononuclear cell accounts for percent value a little more than blank group (P＜0.05), drug withdrawal recovers after 15 days normally, and the lymphocyte of administration 60 days and 15 days high dose group of drug withdrawal accounts for percent value a little less than blank group (P＜0.05); All the other each values are compared zero difference (P＞0.05) with the blank group, belong to the scope of rat normal value, see table 5 for details.
Table 5 rat successive administration 60 days and the drug withdrawal influence to hematologic parameter in 15 days (x ± SD, n=10)
Project blank group supplies reagent object height dosage group for reagent thing low dose group for dosage group in the reagent thing
Administration 60d administration 60d administration 60d administration 60d
Drug withdrawal 15d drug withdrawal 15d drug withdrawal 15d drug withdrawal 15d
WBC?×10
9/L???????????????13.37±2.88???????????????11.18±4.14?????????????????12.21±2.78????????????????????12.46±3.13
12.24±3.19???????????????13.48±2.84?????????????????10.88±4.24????????????????????12.99±3.57
RBC?×10
12/L??????????????8.94±0.84????????????????8.3±0.39???????????????????8.14±0.42?????????????????????8.20±0.36
8.16±1.28????????????????8.35±0.83??????????????????8.61±0.91?????????????????????8.98±0.74
HGB?g/L????????????????????162.2±8.05???????????????153.4±7.46?????????????????151.2±8.78????????????????????152.4±7.95
148.5±20.67??????????????154.1±14.09????????????????158.3±8.11????????????????????162.6±1.77
PLT?×10
9/L???????????????766.3±135.48?????????????655.9±219.81???????????????634.5±178.58??????????????????713.8±155.97
627.5±279.02?????????????583.6±182.58???????????????581.1±113.05??????????????????552.2±139.95
Neutrophilic granulocyte % 20.53 ± 6.41 23.05 ± 8.61 18.85 ± 4.63 33.81 ± 11.50
23.56±6.01???????????????24.98±9.16?????????????????27.86±16.29???????????????????33.92±13.09
Eosinophil leucocyte % 1.013 ± 0.489 0.848 ± 0.238 0.928 ± 0.568 0.892 ± 0.374
1.413±1.651??????????????1.834±1.059????????????????1.678±1.160???????????????????1.479±0.744
Basophil % 0.065 ± 0.042 0.048 ± 0.042 0.050 ± 0.046 0.042 ± 0.035
0.090±0.065??????????????0.096±0.137????????????????0.104±0.164???????????????????0.085±0.097
Lymphocyte % 70.57 ± 7.98 65.93 ± 8.89 71.86 ± 6.15 56.33 ± 12.21*
64.69±9.14???????????????61.98±10.77????????????????58.95±17.00???????????????????53.31±11.51*
Large mononuclear cell % 7.88 ± 2.21 10.12 ± 2.27* 8.32 ± 1.60 8.93 ± 1.77
10.24±2.82???????????????11.09±3.55?????????????????11.52±4.17????????????????????11.25±4.85
Compare with the blank group,
△P＞0.05 (sign is slightly), * P＜0.05;
4, blood biochemistry checking:
For reagent thing basic, normal, high dosage, every blood parameters value of administration two months and drug withdrawal 15d is compared with the blank group, P value there are no significant difference, and (P＜0.05=all belongs to range of normal value.See table 6,7 for details.
The influence to rat hemogram and biochemical indicator in 60 days of table 6 rat successive administration (x ± SD, n=10)
Dosage group high dose group in the project blank group low dose group
ALB??g/L???????????35.17±1.55????????????34.52±5.88?????????33.04±4.54??????????35.48±5.82
ALT??U/L???????????25.49±11.02???????????28.63±14.96????????29.51±8.41??????????27.41±8.27
AST??U/L???????????70.01±11.39???????????77.00±8.13?????????73.33±14.61?????????71.24±9.19
GLU??mMol/L????????6.222±1.232???????????5.807±1.438????????5.107±1.058?????????6.051±1.080
TP??g/L????????????82.3±9.78?????????????74.5±8.05??????????76.9±9.60???????????80.9±6.72
T-CHOL??mMol/L?????1.334±0.354???????????1.312±0.370????????1.396±0.327?????????1.361±0.282
Crea??mg/dl????????0.675±0.282???????????0.666±0.259????????0.844±0.272?????????0.628±0.140
ALP??U/L???????????31.20±11.67???????????33.91±22.78????????39.07±19.86?????????38.25±26.41
BUN??mmol/L????????6.839±1.225???????????7.553±1.084????????6.915±1.495?????????6.614±1.673
Compare with the blank group,
△P＞0.05 (sign slightly);
Table 7 rat successive administration 60 days and the drug withdrawal influence to rat hemogram and biochemical indicator in 15 days
( x±SD，n＝10)
Dosage group high dose group in the project blank group low dose group
ALB??g/L?????????????27.18±3.48???????????29.60±2.93??????????28.86±2.15???????????27.29±1.54
ALT??U/L?????????????30.56±8.64???????????26.54±9.38??????????28.98±11.05??????????29.68±12.51
AST??U/L?????????????81.71±14.63??????????84.33±39.51?????????86.43±46.27??????????91.94±39.11
GLU??mMol/L??????????6.580±1.782??????????5.761±1.062?????????6.362±1.641??????????5.947±1.133
TP??g/L??????????????81.94±13.54??????????78.55±28.64?????????76.72±30.13??????????81.72±22.66
T-CHOL?mMol/L????????1.331±0.494??????????1.653±0.380?????????1.610±0.151??????????1.780±0.202
Crea??mg/dl??????????0.730±0.359??????????0.670±0.106?????????0.750±0.190??????????0.770±0.082
ALP???U/L????????????34.18±19.23??????????30.39±15.12?????????32.01±18.03??????????35.27±10.39
BUN???mMol/L?????????6.880±1.743??????????6.458±1.741?????????7.010±2.932??????????7.075±2.314
Compare P＞0.05 (sign slightly) with the blank group;
5, organ weights and organ coefficient:
For the every internal organs of rat and the internal organs coefficient of the basic, normal, high dosage group of reagent thing, compare with the blank group, difference that there are no significant (P＞0.05), every index is all in normal range.
The exponential influence of rat internal organs in 60 days of table 8 rat successive administration (x ± SD, n=5)
| Group | Body weight | Big brain weight (g) coefficient (10 -2) | Cardiac weight (g) coefficient (10 -1) | Liver weight (g) coefficient (10 -2) | Spleen weight (g) coefficient (10 -3) | Lung weight (g) coefficient (10 -2) | Kidney weight (g) coefficient (10 -2) | Adrenal gland's weight (g) coefficient (10 -4) | Prostate/ovary weight (g) coefficient (10 -3) | Testis/uterus weight (g) coefficient (10 -3) | |
| Blank group | ♂ ♀ | ??208.02±41.14 | ??1.669±0.116 ??8.245±1.438 | ??0.791±0.061 ??3.952±1.015 | ??6.833±0.656 ??3.365±0.546 | ??0.438±0.082 ??2.117±0.665 | ??1.405±0.585 ??6.761±2.163 | ??0.635±0.070 ??3.127±0.513 | ??0.020±0.005 ??0.985±0.228 | ??0.167±0.025 ??0.819±0.147 | ??1.296±0.246 ??6.317±0.936 |
| ??161.06±33.10 | ??1.383±0.490 ??8.986±3.937 | ??0.701±0.052 ??4.511±1.007 | ??5.762±0.552 ??3.720±0.942 | ??0.465±0.157 ??2.985±1.24 | ??1.083±0.092 ??6.925±1.34 | ??0.584±0.061 ??3.721±0.67 | ??0.014±0.005 ??0.88±0.377 | ??0.048±0.019 ??0.299±0.102 | ??0.191±0.053 ??1.245±0.537 | ||
| Low dosage | ♂ ? ? ♀ | ??190.96±8.90 | ??1.705±0.095 ??8.946±0.707 | ??0.693±0.082 ??3.628±0.408 | ??6.44±0.742 ??3.378±0.424 | ??0.480±0.162 ??2.525±0.881 | ??1.257±0.093 ??6.602±0.655 | ??0.598±0.085 ??3.149±0.58 | ??0.018±0.006 ??0.96±0.317 | ??0.156±0.027 ??0.814±0.124 | ??1.16±0.051 ??6.078±2.17 |
| ??186.1±13.18 | ??1.575±0.094 ??8.512±0.926 | ??0.706±0.046 ??3.801±0.291 | ??5.904±0.501 ??3.178±0.261 | ??0.416±0.113 ??2.246±0.665 | ??1.052±0.189 ??5.694±1.24 | ??0.615±0.013 ??3.315±0.217 | ??0.018±0.005 ??0.95±0.285 | ??0.039±0.007 ??0.207±0.035 | ??0.217±0.134 ??1.176±0.75 | ||
| Middle dosage | ♂ ? ? ♀ | ??198.84±16.11 | ??1.737±0.059 ??8.791±0.926 | ??0.709±0.078 ??3.571±0.348 | ??6.140±0.623 ??3.085±0.965 | ??0.644±0.222 ??3.185±0.917 | ??1.063±0.069 ??5.364±0.413 | ??0.601±0.030 ??3.033±0.235 | ??0.018±0.004 ??0.923±0.16 | ??0.171±0.080 ??0.841±0.346 | ??1.333±0.218 ??6.787±1.573 |
| ??157.82±26.86 | ??1.462±0.205 ??9.339±0.834 | ??0.65±0.041 ??4.205±0.659 | ??5.989±0.367 ??3.876±0.633 | ??0.477±0.167 ??3.026±0.957 | ??1.125±0.194 ??7.157±0.627 | ??0.579±0.048 ??3.746±0.623 | ??0.015±0.004 ??0.998±0.453 | ??0.038±0.007 ??0.248±0.077 | ??0.216±0.109 ??1.341±0.541 | ||
| High dose | ♂ ? ? ?♀ | ??196.68±32.27 | ??1.630±0.111 ??8.433±1.177 | ??0.653±0.126 ??3.307±0.2 | ??6.001±1.345 ??3.031±0.209 | ??0.403±0.163 ??2.008±0.56 | ??1.267±0.223 ??6.619±1.822 | ??0.632±0.071 ??3.243±0.293 | ??0.016±0.004 ??0.835±0.335 | ??0.176+0.096 ??0.854±0.418 | ??1.261±0.389 ??6.751±3.051 |
| ??203.24±46.83 | ??1.622±0.041 ??8.326±1.883 | ??0.742±0.174 ??3.781±1.097 | ??6.483±0.880 ??3.252±0.380 | ??0.473±0.099 ??2.347±0.275 | ??1.177±0.162 ??5.975±1.242 | ??0.629±0.108 ??3.192±0.721 | ??0.018±0.005 ??0.912±0.293 | ??0.045±0.016 ??0.242±0.134 | ??0.24±0.035 ??1.218±0.26 | ||
Compare P＞0.05 (labelling is slightly) with blank same sex matched group.
Table 9 rat successive administration 60 days and drug withdrawal 15 days to the exponential influence of rat internal organs (x ± SD, n=5)
| Group | Body weight | Big brain weight (g) coefficient (10 -3) | Cardiac weight (g) coefficient (10 -3) | Liver weight (g) coefficient (10 -2) | Spleen weight (g) coefficient (10 -3) | Lung weight (g) coefficient (10 -3) | Kidney weight (g) coefficient (10 -3) | Adrenal gland's weight (g) coefficient (10 -3) | Prostate/ovary weight (g) coefficient (10 -3) | Testis/uterus weight (g) coefficient (10 -3) | |
| Blank group | ♂ ♀ | ??185.52±39.62 | ??1.697±0.106 ??9.538±2.352 | ??0.724±0.129 ??3.957±0.47 | ??6.504±0.467 ??3.661±0.957 | ??0.489±0.103 ??2.894±1.553 | ??1.253±0.093 ??7.198±2.631 | ??0.655±0.109 ??3.592±0.488 | ??0.016±0.004 ??0.878±0.183 | ??0.152±0.035 ??0.829±0.135 | ??1.049±0.193 ??5.935±1.951 |
| ??161.32±21.81 | ??1.516±0.206 ??9.59±2.23 | ??0.660±0.068 ??4.126±0.473 | ??6.176±0.863 ??3.834±0.269 | ??0.407±0.114 ??2.503±0.418 | ??1.018±0.387 ??6.325±2.196 | ??0.591±0.075 ??3.675±0.25 | ??0.015±0.003 ??0.98±0.308 | ??0.033±0.010 ??0.202±0.066 | ??0.167±0.035 ??1.035±0.145 | ||
| Low dosage | ♂ ♀ | ??152.72±11.68 | ??1.365±0.222 ??8.925±1.205 | ??0.586±0.148 ??3.803±0.712 | ??5.739±0.0678 ??3.749±0.190 | ??0.429±0.259 ??2.749±1.51 | ??1.046±0.143 ??6.846±0.706 | ??0.507±0.055 ??3.318±0.202 | ??0.013±0.003 ??0.838±0.153 | ??0.126±0.025 ??0.817±0.108 | ??1.04±0.291 ??6.869±2.102 |
| ??184.52±10.99 | ??1.682±0.171 ??9.106±0.641 | ??0.688±0.102 ??3.723±0.42 | ??0.990±0.493 ??3.245±0.146 | ??0.441±0.141 ??2.367±0.669 | ??1.260±0.337 ??6.841±1.825 | ??0.629±0.035 ??3.426±0.383 | ??0.017±0.004 ??0.917±0.158 | ??0.041±0.014 ??0.223±0.077 | ??0.196±0.065 ??1.066±0.373 | ||
| Middle dosage | ♂ ♀ | ??184.18±23.27 | ??1.654±0.086 ??9.098±1.191 | ??0.699±0.065 ??3.825±0.421 | ??6.549±0.822 ??3.597±0.576 | ??0.573±0.262 ??3.182±1.602 | ??1.227±0.222 ??6.741±1.329 | ??0.624±0.120 ??3.407±0.627 | ??0.015±0.003 ??0.825±0.172 | ??0.155±0.055 ??0.847±0.284 | ??1.211±0.265 ??6.514±0.707 |
| ??197.93±8.94 | ??1.544±0.019 ??7.817±0.438 | ??0.746±0.056 ??3.776±0.378 | ??6.583±0.412 ??3.331±0.241 | ??0.502±0.061 ??2.541±0.336 | ??1.312±0.143 ??6.632±0.703 | ??0.659±0.037 ??3.329±0.16 | ??0.020±0.005 ??0.993±0.215 | ??0.048±0.025 ??0.241±0.117 | ??0.308±0.082 ??1.544±0.354 | ||
| High dose | ♂ ??♀ | ??204.40±48.76 | ??1.709±0.066 ??8.824±2.595 | ??0.726±0.145 ??3.586±0.246 | ??6.978±1.670 ??3.413±0.145 | ??0.524±0.100 ??2.712±1.005 | ??1.381±0.150 ??7.044±1.775 | ??0.654±0.103 ??3.266±0.398 | ??0.017±0.002 ??0.862±0.262 | ??0.191±0.058 ??0.95±0.24 | ??1.255±0.182 ??6.386±1.603 |
| ??182.93±4.46 | ??1.582±0.096 ??8.647±0.485 | ??0.719±0.053 ??3.936±0.35 | ??6.431±0.492 ??3.518±0.289 | ??0.472±0.74 ??2.582±0.42 | ??1.242±0.165 ??6.788±0.889 | ??0.657±0.040 ??3.59±0.203 | ??0.017±0.007 ??0.916±0.377 | ??0.046±0.008 ??0.249±0.045 | ??0.243±0.090 ??1.323±0.477 | ||
Compare P＞0.05 (labelling is slightly) with blank same sex matched group.
6, the pathology to S.D rat important organ cuts open inspection and histology's spectroscopy:
For behind the basic, normal, high dosage of test agent and continuous percutaneous drug delivery 60d of blank group and the drug withdrawal 15d, divide 2 disconnected vertebras to put to death rat, cut open as pathology and examine internal organs and observe, the result is described below:
Head: skull does not have deformity, and the soft or hard meninges is all no abnormal, and the depth of brain ditch and gyrus is normal, and ventricles of the brain structure is clear, the hypophysis cerebri no abnormality seen.
The heart: visceral pericardium is smooth, no petechia, and myocardium thickness and color and luster no abnormality seen are not seen necrosis of myocardial cell structure or cicatrix, and heart lobe thickness is normal, and chordae tendineae is not seen adhesion, and endocardium is smooth, and arteria coronaria is not seen narrow or sclerosis.
Liver: administration was analysed rat after 60 days, middle dosage group has a Mus (hero) liver that one cavity is arranged, it is dark red that all the other respectively organize the rat color and luster, and smooth surface is moist, and the lobules of liver structure is clear, portal vein district no change, do not see the mainline expansion, no calculus in the biliary tract, bile duct chamber form, as seen that rat of middle dosage group liver anomalies belongs to individual variation, due to the non-given the test agent.
Spleen: hardness, color and luster are all normal, and the tangent plane profile is neatly clear and definite, and no abnormality seen changes.
Lung: administration was analysed rat after 60 days, and it is all normal that each organizes two side lung sizes about rat, hardness, color and luster, and the tangent plane wheel is neat clear and definite, does not see brown induration of lung, did not see that bronchus, aberrant angiogenesis change.
Kidney: administration was analysed rat after 60 days, and rat left and right sides kidney size and hardness color and luster are all normal, and smooth surface is not seen the color film coalescence, and tangent plane skin, medullary substance are had a common boundary clear and definite, and the cortex striped is clear, does not see calculus in the ureter, renal artery wall no abnormality seen.
Testis: size, weight and hardness are all normal, testis contorted seminiferous tubules tool elasticity (available tweezers drawing comes out), epididymis, smart bundle and urethral orifice no abnormality seen.
Uterus and ovary: uterus position, size, shape etc. there is no unusually; Do not see fallopian tube and adjacent organ adhesion, intracavity is not seen obstruction, and the ovary size is normal, lateral symmetry, and color and luster is normal.
For test agent basic, normal, high dosage group rat skin successive administration 60d and after stopping administration 15d, together with the blank group, divide the disconnected vertebra of secondary to put to death rat, after cuing open piece of tissue such as the inspection heart, liver, spleen, lung, kidney, testis, ovary and doing conventional fixing, section, dyeing, microscopy is observed, and the result is described below:
The heart: the muscle fiber structure is clear, does not see muscular degeneration of heart, necrosis, edema or scorching the change, does not see cicatrix; Do not see mucoid or fibrinoid degeneration, do not see the rheumatism brief summary; Valve is not also seen solid edema, does not see necrosis of kitchen range sexual cell or inflammatory cell infiltration, does not see that tissue such as meat tooth forms or phenomenons such as collagen fiber hypertrophy.
Liver: hepatocyte profile and internal structure are clear, do not see cell expansion and inflammatory cell infiltration.
Lung: do not see that alveolar expands, narrow down at interval that phenomenons such as a Kong Bianda do not see that the bronchia inflammatory disease becomes or inflammatory cell infiltration; Do not see in alveolar wall telangiectasis congestion and edema or the alveolar and be full of exudate.
Kidney: peplos does not normally have adhesion, and renal cortex and medullary substance boundary are clear, and renal calices renal pelvis size is normal, does not see that glomerular epithelium hyperplasia or fat become, swelling; Do not see nephridial tissue destruction, hyperemia, edema or inflammatory cell infiltration.
Testis: cell is arranged normal; The structure no abnormality seen; Do not see organic disease or inflammation.
Uterus: do not see the glandular epithelium hyper-proliferative, do not see between fine hair between the treating serious edema caused or fine hair of matter that blood vessel disappears in the matter, do not see trophoderm epithelial cell height hypertrophy.
Ovary: cortex medullary substance structure is clear, does not see tissue degeneratiaon or scorching the change, does not see ovarian cyst or achiblastoma.
More than cut open inspection observation and pathology microscopy and show, do not find the change of toxic reaction and pathologic lesion for the main organs of basic, normal, high dosage group of test agent and blank group rat.
Four, conclusion (of pressure testing)
Show from above result of the test; With continuous two months of SD rat with dividing high, medium and low three dosage to percutaneous drug delivery for the reagent thing, the lymphocyte that administration 60 days and drug withdrawal supplied test agent to remove the high dose group rat in 15 days accounts for percent value a little less than blank group (P＜0.05), any abnormal response does not appear in all the other each treated animals, no death or weight loss, hematology, blood biochemistry checking are not seen obvious influence yet, do not have influence to ingesting, drinking water.Illustrate for dosage (65cm in the test agent
2) be safe dose, calculate 32.5 times that are equivalent to the clinical consumption of people by body surface area.
[test example 4] pharmaceutical composition of the present invention is to the effect of mice analgesic test
One, test material
1, for the reagent thing: the external plaster sheet that the embodiment of the invention is prepared;
2, blank excipient, for not containing the plaster sheet of medicine, it is standby to be cut into required area during experiment.
3, positive control drug: Aspirin Enteric-coated Tablets.The per day for adults consumption of 70Kg is 1.8g, is 1.8g ÷ 387.9 * 50=0.23g/Kg body weight through being converted into the mice consumption, irritates stomach 0.4ml for every.
4, laboratory animal: NIH is a mice, and body weight 20 ± 2g is provided by Guangdong Medical Lab Animal Center, the laboratory animal quality certification number: 99A030.
Two, test method and result
1, to mice analgesic test (hot plate method)
Choose 70 of adult healthy mices, body weight is 20 ± 2g, is female entirely, mice is put on the thermostat metal plate of 55 ℃ in hot plate analgesia instrument (room temperature is 20 ± 2 ℃), with skirt, lick metapedes, jump etc. as indicator reaction bitterly.Select for use the response latency to be no more than the mice of 30s.Measure the threshold of pain (survey secondary altogether, be no more than 30s person for qualified) of every mice earlier with meansigma methods.5 dosage groups are set, are respectively blank vehicle group, supply reagent, low dose group, middle dosage group, high dose group and positive controls, every group of 10 mices.To respectively organize the mouse back hair for reagent thing group with the elbow shears cuts off, dip in depilatory (Containing Sulfur sodium 8g, starch 7g, sugared 4g with cotton balls, glycerol 5g, Borax 1g adds water 75ml), be coated with gently at guinea pig back, clean the depilation part with warm water after 3 minutes, dry with gauze, about 7 * 7 square centimeters, its depilation area accounts for about 25% of body surface area.The positive controls mice is irritated with aspirin 0.0116g/ml solution, irritates stomach 0.4ml for every.Measure behind the administration 1.0h.Blank group is pasted with blank excipient, and other each groups are pasted for the back of reagent thing in mice.Its dosage is respectively 1,3,9 times of adult.The adult of 70Kg is that (every veneer is long-pending to be 2 * 6.2 * 9.0cm in 2 subsides/skies for the use amount of reagent thing
2), being converted into average weight and being the area that the mice of 20g should paste is low dose group 0.4 * 0.7cm
2, middle dosage group 1.2 * 0.7cm
2, high dose group 1.4 * 2.1cm
2
Mice is put on the metallic plate of 55 ℃ in hot plate analgesia instrument, with skirt, lick metapedes, jump etc. as indicator reaction bitterly.Surpass 60 seconds i.e. expression has analgesic activity incubation period after the medication, should take out mice immediately, prevents to scald tail and influence experimental result.Begin after the administration to measure, drop into hot plate to the pain threshold of the time that metapedes occurs licking (s) certainly as this Mus with stopwatch record mice.Measure once every 0.5h, continuous four times, surpass 60s as pain threshold, promptly stop test and by 60s.When experiment finishes, improve percentage rate by the mean value calculation threshold of pain of being surveyed, the threshold of pain.
Percentage rate=(the preceding average pain threshold of average pain threshold-medication after the medication)/preceding average pain threshold of medication is improved in the threshold of pain
Table 10 for the reagent thing to the effect of mice hot plate analgesic test (x ± SD, n=10)
| Project | Before the administration (S) | After the administration (S) | |||
| ????0.5h | ????1.0h | ????1.5h | ????2.0h | ||
| Blank group | ????8.3±2.4 | ????8.2±4.4 | ????8.1±5.5 | ????7.9±2.7 | ????8.6±2.2 |
| Low dose group | ????8.4±3.0 | ????10.8±3.9 | ????12.4±3.6 | ????14.8±3.2*** | ????13.7±4.6** |
| Middle dosage group | ????8.2±2.3 | ????10.5±2.7 | ????16.2±4.4*** | ????27.8±12.5*** | ????22.8±9.7*** |
| High dose group | ????9.8±2.3 | ????29.9±16.6*** | ????36.9±11.3*** | ????45.0±11.7*** | ????34.7±10.0*** |
| Positive controls | ????8.8±1.8 | ????36.1±12.0*** | ????44.3±9.4*** | ????51.2±7.5*** | ????42.2±8.7*** |
Compare with the blank group,
P＞0.05, * P＜0.05, * * P＜0.01, * * * P＜0.001.
2, to mice analgesic test (chemical method)
Choose 50 of adult healthy mices, body weight is 22 ± 2g, male and female half and half. 5 dosage groups are set, be respectively blank vehicle group, for reagent thing low dose group, middle dosage group, high dose group and positive controls are lost hair or feathers and administration by experiment 1, begin experiment behind the administration 1.0h, the about 0.2ml/ of every Mus lumbar injection chemical irritant 1% acetic acid only, can cause the deep, large tracts of land and more persistent pain stimulation, cause mice to produce " turn round body " reaction, as abdominal part indent (being the wasp waist shape), trunk and back leg are upheld, hips up etc.Analgesic has inhibitory action to this, can obviously reduce generation " turn round body " number of mice of reaction. each Mus is turned round the body number of times, the comparable group differences in the record injection algogen 20min.
The analgesia percentage rate of medicine=(administration group number of times-blank group number of times)/blank group number of times
Table 11 for the reagent thing to mice analgesic test (chemical method) (x ± SD, n=10)
| The blank group | Low dose group | Middle dosage group | High dose group | Positive controls | |
| Turn round body number (n) | 98.1±10.2 | ????58.5± ????????5.9*** | ????51.0± ????????5.0*** | ????40.9± ????????9.6*** | ??33.7± ????3.7*** |
| The analgesia percentage rate | ---- | ????40.4％ | ????48.0％ | ????58.3％ | ??65.6％ |
Compare * * * P＜0.001. with the blank group
Conclusion:
1) by hot plate analgesic experiment result as can be known, can effectively improve the pain threshold of mice for the basic, normal, high dosage group of reagent thing, compare with the blank group, have significant differences, prompting has significant analgesia role for the reagent thing;
2) by chemical method analgesic experiment result as can be known, can effectively suppress the pain that acetic acid causes for the reagent thing, for the basic, normal, high dosage of reagent thing mice is respectively 40.4%, 48.0%, 58.3%, prompting has significant analgesia role for the reagent thing.
[test example 5] medicine antiinflammatory pharmacological research of the present invention
One, test material
1, for the reagent thing: the plaster sheet that the embodiment of the invention is prepared; The adult of 70Kg is that (area is 2 * 6.2 * 9.0cm in 2 subsides/skies for the use amount of reagent thing
2), being converted into body weight by body surface area is that the area that the mice of 20g should be pasted is low dose group 0.4 * 0.7cm
2, middle dosage group 1.2 * 0.7cm
2, high dose group 1.2 * 2.1cm
2, its dosage is respectively 1,3,9 times of adult.Being converted into body weight by body surface area is that the area that the rat of 200g should be pasted is low dose group 2.0 * 1.0cm
2, middle dosage group 3.0 * 2.0cm
2, high dose group 3.0 * 6.0cm
2, its dosage is respectively 1,3,9 times of adult.
2, blank excipient: provide by Foshan Dezhong Pharmaceutical Co., Ltd.
3, positive control drug: Aspirin Enteric-coated Tablets, Hunan pharmaceutical factory produces, and the accurate word (1989) of medicine is defended No. 001157 in Hunan.The per day for adults consumption of 70Kg is 1.8g, is 1.8g ÷ 387.9 * 50=0.23g/Kg body weight through being converted into the mice consumption, irritates stomach 0.4ml for every.Through being converted into the rat consumption is 1.8g ÷ 56 * 20=0.64g/Kg body weight, irritates stomach 1.0ml for every.
4, proinflammatory agent: dimethylbenzene, analytical pure, Guangzhou Chemical Reagent Factory production.
5, laboratory animal: NIH is a mice, and body weight 20 ± 2g is provided by Guangdong Medical Lab Animal Center, the laboratory animal quality certification number: 99A030.Laboratory animal, the SD rat, 200 ± 20g, male, qualified 99A046 is provided by No.1 Military Medical Univ.'s Experimental Animal Center.
Two, test method and result
1, xylol causes the effect of mice auricle swelling
Choose 50 of adult healthy mices, body weight 26～30g is male entirely.5 dosage groups are set, are respectively blank vehicle group, supply reagent thing low dose group, middle dosage group, high dose group and positive controls, every group of 10 mices.
Route of administration: will respectively organize the mouse back hair for reagent thing group with the elbow shears and cut off, dip in depilatory (Containing Sulfur sodium 8g, starch 7g, sugared 4g with cotton balls, glycerol 5g, Borax 1g adds water 75ml), be coated with gently at mouse back, clean the depilation part with warm water after 3 minutes, dry with gauze, rested one day, press the dosage percutaneous drug delivery.Blank group is pasted with blank excipient.
During the experiment beginning, carry out proinflammatory effect.Dimethylbenzene 0.05ml is dripped auris dextra in mice, in contrast with left ear.Each is organized mice and gives proinflammatory agent administration respectively in preceding 1.5 hours, after 0.5 hour mice being taken off cervical vertebra behind the proinflammatory agent puts to death, cut two ears along the auricle baseline, with the card punch of diameter 9mm respectively about the same position of two ears lay round auricle, weigh, the difference of asking left and right auricle weight is as the swelling degree, comparable group differences significance.The swelling rate=(auris dextra weight-left ear is heavy)/left ear is heavy.Result of the test sees Table 12.
Table 12 for the reagent thing to the effect of mice dimethylbenzene induced mice auricle edema (x ± SD, n=10)
| Project | The blank group | High dose group | Middle dosage group | Low dose group | Positive controls |
| Weight (auris dextra-left ear) (g) | ???0.0153±0.00 ???5 | ??0.0081±0.00 ??4 | ?0.085±0.003 | ??0.0104±0.00 ??5 | ?0.0101±0.00 ?5 |
| Left side ear weight (g) | ???0.0133±0.00 ???2 | ??0.0155±0.00 ??2 | ?0.0162±0.00 ?2 | ??0.0148±0.00 ??2 | ?0.0130±0.00 ?2 |
| Swelling rate (%) | ???120.8±51.7 | ??52.4±25.9** ??* | ?55.5±26.6** | ??71.9±37.0* | ?81.2±42.6* |
Compare * P＜0.05, * * P＜0.01, * * * P＜0.001. with the blank group
2, to the bullate influence of rat granuloma
Selecting healthy SD is rat, male, with the elbow shears rat back hair is cut off, dip in depilatory (Containing Sulfur sodium 8g with cotton balls, starch 7g, sugared 4g, glycerol 5g, Borax 1g, add water 75ml), be coated with gently at guinea pig back, clean the depilation part with warm water after 3 minutes, dry with gauze, about 5 * 5 square centimeters, its depilation area accounts for about 25% of body surface area, after the anesthesia of 30mg/kg pentobarbital sodium, the 25mg cotton balls of the same size of will weighing, through autoclaving, each cotton balls adds procaine benzylpenicillin 1mg/0.1ml again, behind 50 ℃ of stove-dryings, hit exactly neat upper limb place in the rat chest and vertically cut off the about 1～1.5cm of skin, to the subcutaneous implantation cotton balls of both sides axillary fossa.Behind the sew up wound, be respectively blank vehicle group at random, supply reagent thing low dose group, middle dosage group, high dose group and positive controls, every group of 10 rats.Operation rose the same day, and intramuscular injection procaine benzylpenicillin 4000U/ only injected 4 days continuously, began administration simultaneously after 12 days, put to death animal, take out cotton balls, peel off fatty tissue, weigh after putting 60 ℃ of oven dry of baking oven, gained weight is deducted cotton balls weight, be granuloma weight.Result of the test sees Table 13.
Table 13 for the reagent thing to the bullate influence of rat granuloma (x ± SD)
| Group | Number of animals (n) | Granuloma weight (mg) | Suppression ratio (%) |
| The blank group | ??10 | ?295.5±32.8 | --- |
| Positive controls | ??10 | ?202.7±35.5 *** | 31.5 |
| Low dose group | ??10 | ?278.4±15.6 △ | 5.8 |
| Middle dosage group | ??10 | ?270.2±15.6 ** | 15.6 |
| High dose group | ??10 | ?242.4±44.6 ** | 18.0 |
Compare with the blank group,
△P＞0.05, * * P＜0.01, * * * P＜0.001.
Conclusion:
1) by mice caused by dimethylbenzene xylene auricle edema model experiment result as can be known, compares, can obviously suppress the mice caused by dimethylbenzene xylene auricle edema, have significant difference for the basic, normal, high dosage group of reagent thing with the blank group.
2) by the swollen experimental result of rat granuloma as can be known, can effectively suppress the cotton granulomatous formation of rat for the middle and high dosage of reagent thing, compare with the blank group, its suppression ratio is respectively 15.6% and 18.0%, has significant differences.The above results all shows for the reagent thing to have antiinflammatory action.
The clinical efficacy and the safety testing thereof of [test example 7] medicine composite for curing lumbago due to renal deficiency of the present invention
Clinical trial protocol is worked out with reference to " provisions for new drugs approval ", " new Chinese medicine clinical research guideline ".Specify by Guangdong Province's medicine management department, clinical trial is responsible for by No.2 Hospital Attached to Guangzhou Traditional Chinese Medicial Univ clinical drug study base, and The First Affiliated Hospital of Guangzhou University of Traditional Chinese Med, attached sun yat-sen memorial hospital of Zhongshan Medical Univ., three hospitals of Guangzhou City Traditional Chinese Medicine Hospital participate in jointly.Clinical trial in February, 2000 to 2000 year JIUYUE carry out and finish.Now 411 routine clinical test results are summarized as follows:
One, the selection of qualified study subject
(1) diagnostic criteria
1, names of disease of tcm diagnosis:
(1) lumbago diagnostic criteria
1. typical one or both sides flank pain symptom
2. the medical history of showing effect repeatedly can be arranged
3. get rid of stranguria, edema, tumor and menoxenia, gestation etc. with the lumbago symptom
2, Chinese medical discrimination standard:
(1) nephrasthenia syndrome:
Primary symptom: waist is aching and limp, or continuously has a pain, happiness rub by, meet labor what for, for sleeping in then alleviation of pain.
Inferior disease: 1. knee is aching and limp unable, 2. muscular soreness, 3. hands and feet being not warm, 4. frequent micturition, or frequent urination at night (more than 2 times), 5. dribble of urine not to the utmost, 6. seminal emission, 7. premature ejaculation, 8. hyposexuality
Picture of the tongue: pale tongue or light fat, white and thin fur.
Pulse condition: a little less than thin and delicate or heavy.
Primary symptom and corresponding tongue pulse condition possess, and 2 of inferior diseases are promptly diagnosable.
(2) the double cold-damp syndrome of suffering from a deficiency of the kidney:
1. waist is aching and limp, and cold type of pain is weighing, and must hotly then subtract, and it is unfavorable to change one's position
2. meet the outbreak of overcast and rainy pain or increase the weight of, even lumbago does not subtract and increases the weight of when reposing
3. joint joint stuffiness
4. moderate pulse or string
5. pale tongue, Tai Bai or white thick or white greasy
Meet the nephrasthenia syndrome standard and have that above-mentioned 1. 2. 3. Xiang Zhongren binomial and the tongue pulse condition person of conforming to are the double cold-damp syndrome of suffering from a deficiency of the kidney.
3, Western medicine diagnose standard:
(1) chronic lumbar muscle strain (comprising chronic fatigue damages such as waist muscle, fascia, ligament).
1. have or do not have acute strain history, but the repeated multiple times outbreak.
2. often chronic problem or mild pain, sitting and bend over lastingly or waist when movable pain increase the weight of.One or both sides waist section musculus sacrospinalis has tenderness, and the waist mobility is limited slightly.
3. the X line is taken the photograph sheet eliminating bone lesion.
(2) lumbar vertebra hyperosteogeny disease
1. waist is ached and can be shown effect repeatedly.
2. lumbago pain after rest increases, and can alleviate after the activity slightly, but movable back pain increases the weight of.
3. the X line is taken the photograph sheet: lumbar vertebra body forward position or tailing edge hyperosteogeny sign are arranged.
(2) include standard in:
The lumbago due to renal deficiency patient who meets the above-mentioned traditional Chinese medical science and Western medicine diagnose standard
(3) exclusion standard:
1, do not meet above-mentioned Chinese medical discrimination, Western medicine diagnose standard person
2, by spinal cord or nerve injury person (as the os pelvicum fracture person) is arranged or sick caused lumbago patient such as rheumatoid arthritis, ankylosing spondylitis, urinary stone, infection, tumor,
3, anemia of pregnant woman or women breast-feeding their children
4, be associated with serious primary disease such as cardiovascular, liver, kidney and hemopoietic system, psychotic
5, confirm on inspection by the dysmenorrhea patient due to pelvic inflammatory disease, endometriosis, the uterus tumor
6, treatment noncooperationist
7, researcher is thought and should not carry out clinical trial person
Two, clinical implementation scheme
(1) test grouping: adopt single at random blind controlled trial research method.
Be not more than 3: 1 and carry out case by the ratio of treatment group and matched group case load and distribute.Treatment is organized more than 300 examples, more than matched group 100 examples.Clinical trial is observed simultaneously in four hospitals, and patient can be and is in hospital and the outpatient.
The method of simple randomization is adopted in the case grouping.Concrete randomization distribution method is by the random by key (INV of No.2 Hospital Attached to Guangzhou Traditional Chinese Medicial Univ clinical drug study base clinical research personnel by operation Casio (fx-3600p) computer, RAN) draw random digit, and make the random assortment card, add the envelope sealing, the envelope sequence number is identical with the card sequence number, send and respectively participates in test unit.When qualified case enters test,, take the identical envelope of number apart, treat by the grouping of card regulation in the envelope by its precedence that enters.
(2) selection of contrast medicine
Special dog skin plaster, commercially available, produce by Dongling Pharmaceutical Co., Ltd., Shenyang.
(3) usage, dosage
The treatment group: the emplastrum (comprising rubber-emplastrum, cataplasma, patch) that the embodiment of the invention is prepared, external is affixed on either side of the small of the back cave, waist both sides or adds and was affixed on Guanyuan acupoint 12 hours, and pain disease is pasted the affected part.
Matched group: special dog skin plaster, external was pasted the affected part 12 hours.
(4) course of treatment: all around
(5), blind method is implemented (single blind):
The emplastrum that the embodiment of the invention is prepared (comprising rubber-emplastrum, cataplasma, patch) (comprising rubber-emplastrum, cataplasma, patch) is used identical outer package instead with special dog skin plaster, again label, its called after the kidney invigorating cream I number or the kidney invigorating cream II number.
(6), observation index
1, general data: sex, age, the course of disease, Western medicine diagnose, Chinese medical discrimination etc.
2, safety observation project
(1) the untoward reaction symptom of answering close observation to occur clinically is as diarrhoea, dizziness, headache, erythra etc.
(2) routine urinalysis, routine blood test, stool routine examination (1/3 experimenter detects before and after treating)
(3) electrocardiogram, liver function (GPT), renal function (BUN) (1/3 experimenter detects before and after treating)
3, health giving quality observation project
(1) position of lumbago, character, degree, active situation
(2) symptom, picture of the tongue, pulse condition etc. of cold-damp syndrome held concurrently of suffering from a deficiency of the kidney, suffer from a deficiency of the kidney
(3) symptom, sign grading
1. lumbago grading
0 grade: no pain
I level (slightly): the lumbago idol has outbreak, has a dull ache, and does not influence routine work
II level (moderate): lumbago is heavier, and it is unfavorable to change one's position, and inconvenient activity or lumbago are indistinct, and outbreak influences routine work again and again
III level (severe): waist severe pain, unable to move around, then pain is acute to play the seat activity, can not adhere to work, or lumbago continues person more than month
2. muscular soreness grading
0 grade: no muscular soreness
The I level: muscular soreness is slight, and idol has outbreak, does not influence routine work
The II level: muscular soreness is obvious, and often outbreak still can be stood, and influences routine work
The III level: muscular soreness is violent, is difficult to stand, and painful expression is arranged, and the work that has a strong impact on is had a rest
3. joint stuffiness grading:
0 grade: no joint stuffiness
The I level: movable function is slightly limited, still can bend to functional position
The II level: movable function is obviously limited, and dysfunction is in 10 °
The III level: movable function is seriously limited, and dysfunction is more than 10 °
4. waist movable function:
Anteflexion:
0 grade: 〉=90 ° (normally)
I level: 70 °～90 °
II level :≤70 °
Layback:
0 grade: 〉=30 ° (normally)
I level: 10 °～30 °
II level :≤10 °
Bend in the left side:
0 grade: 〉=20 ° (normally)
I level:＜20 °
Bend on the right side:
0 grade: 〉=20 ° (normally)
I level:＜20 °
(4) picture of the tongue:
Body of the tongue: light, light red, red
Tongue fur: white, thin white, white greasy, BOHUANG
(5) pulse condition: normal pulse, thin, weak, string, slow, heavy
(6) waist X line is taken the photograph sheet (checking before the treatment)
(7), observational technique
Clinical symptoms, sign should be before treatments, observe weekly, write down 1 time after treating.
Routine urinalysis, routine blood test, stool routine examination, electrocardiogram, liver function (GPT), renal function (BUN) detect before and after treating.
Waist X line is taken the photograph sheet and is treated preceding inspection.
(8), follow up a case by regular visits to
The course of treatment, efficacy determination was that the patient of clinical cure all need carry out following up a case by regular visits in two weeks of drug withdrawal when finishing, and observed long-term effect.
Three, curative effect determinate standard:
1, clinical cure:
Lumbago and sign thereof all disappear, and do not influence activity and work, follow up a case by regular visits to for two weeks and do not have recurrence
2, produce effects:
Lumbago and sign thereof obviously alleviate, and do not influence work and rest to, or the state of an illness are transferred slightly by severe
3, effective:
Lumbago and sign thereof alleviate or improve, and unstable condition has recurrence after the drug withdrawal
4, invalid:
Clinical symptoms and sign do not have significant change or increase the weight of
Four, clinical summary and statistical procedures
Clinical observation finishes all data of back and gathers, and the input computer is set up the data base, carries out data statistics and handles, and is summarized by the clinical research responsible department at last, and objective evaluation is carried out in the clinical efficacy and the safety thereof of waist kidney cream treatment lumbago due to renal deficiency.
Statistical method: group data X
2Check, ranked data be with the relatively Wilcoxon rank test (corrections) of two samples, and two sample means are relatively with the t check, and rank test is relatively matched with paired t-test or Wilcoxon in self front and back.
One, physical data
Total qualified experimenter's 411 examples, 311 examples are organized in treatment, matched group 100 examples; Western medicine diagnose is chronic lumbar muscle strain 172 examples, and lumbar vertebra hyperosteogeny disease 239 examples (prompting of X ray examination: lumbar vertebra hyperosteogeny 239 examples, do not see sclerotin disease 172 examples); Chinese medical discrimination is nephrasthenia syndrome 315 examples, cold-damp syndrome 96 examples of holding concurrently of suffering from a deficiency of the kidney.Treatment group inpatient 41 examples, matched group inpatient 9 examples, all the other are the outpatient.
Two, two groups of comparabilities are checked
1, two groups of ages (year) relatively
The table 14 liang group age (year) relatively
Group example number 18-30 31-50 51-65＞65 x ± s
Treatment organizes 311 35 148 111 17 47.53 ± 12.15
Matched group 100 13 41 43 3 47.74 ± 11.88
X
2＝0.106??????????????????????????t＝0.15
P＝0.745?????????????????????????????P＝0.88
Two groups of age ratios, difference does not have the significance meaning.
2, two groups of sex ratios
Table 15 liang group sex ratio
Group example number men and women
Treatment organizes 311 137 174
Matched group 100 46 54
X
2＝0.12?????P＝0.73
Two groups of sex ratios, difference does not have the significance meaning.
3, two groups of tcm syndromes relatively
Table 16 liang group tcm syndrome relatively
The group example number nephrasthenia syndrome double cold-damp syndrome of suffering from a deficiency of the kidney
Treatment organizes 311 237 74
Matched group 100 78 22
X
2＝0.14???????????P＝0.71
Two groups of tcm syndromes compare, and difference does not have the significance meaning.
4, two groups of sick kinds relatively of doctor trained in Western medicine
Table 17 liang sick kind of group doctor trained in Western medicine compared
Group example number chronic lumbar muscle strain lumbar vertebra hyperosteogeny
Treatment organizes 311 132 179
Matched group 100 40 60
X
2＝0.19???????????P＝0.67
Two groups of sick kinds relatively of doctor trained in Western medicine, difference does not have the significance meaning.
5, two groups of courses of disease (duration of seizure recently) relatively
The table 18 liang group course of disease (duration of seizure recently) relatively (moon)
*
Group example number≤1 2-12 13-24＞24
Treatment organizes 297 40 51 24 182
Matched group 97 19 36 8 34
X
2＝24.17????P＜0.001
* 14 examples are organized in treatment, matched group 3 example record disappearances
Two groups of nearest duration of seizure of lumbago compare, and difference has the significance meaning.
6, two groups of preceding lumbago severity extents of treatment relatively
The lumbago severity extent relatively before the table 19 liang group treatment
*
The slight moderate severe of group example number
Treatment organizes 311 44 191 76
Matched group 100 21 67 12
Rank test u=2.78 P=0.0056
*The lumbago grading:
0 grade: no pain
I level (slightly): the lumbago idol has outbreak, has a dull ache, and does not influence routine work
II level (moderate): lumbago is heavier, and it is unfavorable to change one's position, and inconvenient activity or lumbago are indistinct, and outbreak influences routine work again and again
III level (severe): waist severe pain, unable to move around, then pain is acute to play the seat activity, can not adhere to work, or lumbago continues person more than month
The lumbago severity extent compares before two groups of treatments, and difference has the significance meaning.
7, two groups of preceding lumbago character of treatment relatively
Lumbago character relatively before the table 20 liang group treatment
Hot then continuous work is met labor pain when then pain crouches that then crouches
The group cold type of pain pain relieved by pressing of aching is rubbed
Subtracting pain very subtracts
Treatment organizes 272 99 153 209 226 260 180 45
Matched group 89 26 46 71 79 86 53 9
X
2?????????0.17??????1.22?????0.31???????0.50????1.58?????0.33????????0.73????????1.98
P???????????0.68??????0.27?????0.58???????0.48????0.21?????0.57????????0.39????????0.16
Lumbago character compares before two groups of treatments, and difference does not have the significance meaning.
8, two groups of preceding muscular soreness of treatment relatively
Muscular soreness relatively before the table 21 liang group treatment
*
The several 0 grade of I level II level III level of group example
Treatment organizes 311 11 100 167 33
Matched group 100 3 45 42 10
Rank test u=1.786 P=0.074
*The muscular soreness grading:
0 grade: no muscular soreness
The I level: muscular soreness is slight, and idol has outbreak, does not influence routine work
The II level: muscular soreness is obvious, and often outbreak still can be stood, and influences routine work
The III level: muscular soreness is violent, is difficult to stand, and painful expression is arranged, and the work that has a strong impact on is had a rest
Muscular soreness compares before two groups of treatments, and difference does not have the significance meaning.
9, two groups of preceding joint stuffiness of treatment relatively
Joint stuffiness relatively before the table 22 liang group treatment
*
The several 0 grade of I level II level III level of group example
Treatment organizes 311 22 138 111 40
Matched group 100 7 46 40 7
Rank test u=0.658 P=0.511
*The joint stuffiness grading:
0 grade: no joint stuffiness
The I level: movable function is slightly limited, still can bend to functional position
The II level: movable function is obviously limited, and dysfunction is in 10 °
The III level: movable function is seriously limited, and dysfunction is more than 10 °
Joint stuffiness compares before two groups of treatments, and difference does not have the significance meaning.
10, two groups of treatment front waist movable functions relatively
Anteflexion function ratio before the table 23 liang group treatment
*
The several 0 grade of I level II level of group example
Treatment organizes 311 45 194 72
Matched group 100 15 69 16
Rank test u=1.153 P=0.249
*Anteflexion functional classification:
0 grade: 〉=90 ° (normally)
I level: 70 °～90 °
II level :≤70 °
Face upward function ratio before and after the table 24 liang group treatment
*
The several 0 grade of I level II level of group example
Treatment organizes 311 57 199 55
Matched group 100 25 63 12
Rank test u=1.79 P=0.074
*The layback functional classification:
0 grade: 〉=30 ° (normally)
I level: 10 °～30 °
II level :≤10 °
Function ratio is bent in the left side before the table 25 liang group treatment
*
The several 0 grade of I level of group example
Treatment organizes 311 156 155
Matched group 100 52 48
X
2＝0.10???P＝0.749
*Function is bent in the left side:
0 grade: 〉=20 ° (normally)
I level:＜20 °
Function ratio is bent in the table 26 liang preceding right side of group treatment
*
The several 0 grade of I level of group example
Treatment organizes 311 178 133
Matched group 100 52 48
X
2＝0.84?????P＝0.36
*Function is bent on the right side:
0 grade: 〉=20 ° (normally)
I level:＜20 °
Bend in anteflexion, layback before two groups of treatments, left side, function ratio is bent in the right side, and difference does not have the significance meaning.
11, two groups of preceding other clinical symptoms of treatment relatively
Other clinical symptoms relatively before the table 27 liang group treatment
The heeltap behind the aching and limp frequent micturition of knee, the nocturia
Group hands and feet being not warm seminal emission premature ejaculation hyposexuality
Unable frequent micturition not to the utmost
Treatment organizes 255 95 180 43 15 17 62
Matched group 79 27 57 833 20
X
2(or correction) 0.45 0.46 0.02 2.36 0.24 0.53 0.00
P???????????0.50???????0.499????????0.88????????0.124??????0.62??????0.47??????0.99
Other clinical symptoms compares before two groups of treatments, and difference does not have the significance meaning.
12, two groups of preceding picture of the tongues of treatment, pulse conditions compare
Body of the tongue relatively before the table 28 liang group treatment
Group example number is light red
Treatment organizes 311 180 131
Matched group 100 62 38
X
2＝0.53???P＝0.466
Body of the tongue compares before two groups of treatments, and difference does not have the significance meaning.
Tongue fur relatively before the table 29 liang group treatment
Group example number is thin in vain greasy in vain
Treatment organizes 311 70 195 46
Matched group 100 21 66 13
X
2＝0.38???P＝0.828
Tongue fur compares before two groups of treatments, and difference does not have the significance meaning.
Pulse condition relatively before the table 30 liang group treatment
The slow string of the flat thin and delicate heavy weak number of group example number
Treatment organizes 311 13 168 53 5 72
Matched group 100 7 46 17 3 27
X
2(correction)=3.39 P=0.49
Pulse condition compares before two groups of treatments, and difference does not have the significance meaning.
Comparability detects and shows before the above-mentioned treatment, except that treatment group lumbago degree overweights matched group, the treatment group course of disease is longer than the matched group (will organize the comparison of a curative effect in efficacy analysis), comparisons such as sick kinds of age, sex, tcm syndrome, doctor trained in Western medicine, lumbago character, muscular soreness, joint stuffiness, waist movable function, other clinical symptoms and picture of the tongue, pulse condition before two groups of treatments, difference there are no significant meaning.The principal element that prompting influences two groups of prognosis has harmony.
Three, curative effect relatively
1, total effects relatively
Table 31 total effects relatively
Clinical cure produce effects enabledisable
Group example number
(％)????????????(％)????????(％)????????(％)
Treatment organizes 311 51 150 88 22
(16.4)??????????(48.2)??????(28.3)??????(7.1)
Matched group 100 7 37 48 8
(7.0)???????????(37.0)??????(48.0)??????(8.0)
Rank test u=3.587 P=0.00033
Treatment group clinical cure rate is 16.4%, and obvious effective rate is 48.2%, and effective percentage is 28.3%, and clinical cure and obvious effective rate are 64.6%, and total effective rate is 92.9%; The matched group clinical cure rate is 7.0%, and obvious effective rate is 37.0%, and effective percentage is 48.0%, and clinical cure and obvious effective rate are 44.0%, and total effective rate is 92.0%.Two groups relatively, and difference has the significance meaning.
2, two groups of different sick curative effects of planting compare
The different sick curative effects relatively (rank test) of planting of table 32 liang group
The produce effects enabledisable
Group example number clinical cure (%) u P
(％)??????????(％)??????(％)
Treatment organizes 132 28 60 37 7 1.36 0.17
Chronic psoas muscle
(21.2)??????????(45.5)????????(28.0)????(5.3)
Strain
Matched group 40 4 19 16 1
(10.0)??????????(47.5)????????(40.0)????(2.5)
Treatment organizes 179 23 90 51 15 3.53 0.0004
Lumbar vertebrae bone
(12.8)??????????(50.3)????????(28.5)????(8.4)
Hypertrophy disease
Matched group 60 3 18 32 7
(5.0)???????????(30.0)????????(53.3)????(11.7)
Chronic lumbar muscle strain: treatment group clinical cure rate is 21.2%, and obvious effective rate is 45.5%, and effective percentage is 28.0%, and clinical cure and obvious effective rate are 66.7%, and total effective rate is 94.7%; The matched group clinical cure rate is 10.0%, and obvious effective rate is 47.5%, and effective percentage is 40.0%, and clinical cure and obvious effective rate are 57.5%, and total effective rate is 97.5%.Two groups relatively, and difference does not have the significance meaning.
Lumbar vertebra hyperosteogeny disease: treatment group clinical cure rate is 12.8%, and obvious effective rate is 50.3%, and effective percentage is 28.5%, and clinical cure and obvious effective rate are 63.1%, and total effective rate is 91.6%; The matched group clinical cure rate is 5.0%, and obvious effective rate is 30.0%, and effective percentage is 53.3%, and clinical cure and obvious effective rate are 35.0%, and total effective rate is 88.3%.Two groups relatively, and difference has the significance meaning.
3, two groups of different tcm syndrome curative effects relatively
The table 33 liang different tcm syndrome curative effects of group are (rank test) relatively
The produce effects enabledisable
Group example number clinical cure (%) u P
(％)????????(％)????????(％)
Treatment organizes 237 41 114 67 15 3.27 0.0011
Nephrasthenia syndrome (17.3) (48.1) (28.3) (6.3)
Matched group 78 5 29 41 3
(6.4)??????????????(37.2)??????(52.6)??????(3.8)
Treatment organizes 74 10 36 21 7 1.57 0.117
Suffering from a deficiency of the kidney, it is cold to hold concurrently
(13.5)?????????????(48.6)??????(28.4)??????(9.5)
Damp syndrome
Matched group 22 2875
(9.1)??????????????(36.4)??????(31.8)??????(22.7)
Nephrasthenia syndrome: treatment group clinical cure rate is 17.3%, and obvious effective rate is 48.1%, and effective percentage is 28.3%, and clinical cure and obvious effective rate are 65.4%, and total effective rate is 93.7%; The matched group clinical cure rate is 6.4%, and obvious effective rate is 37.2%, and effective percentage is 52.6%, and clinical cure and obvious effective rate are 43.6%, and total effective rate is 96.2%.Two groups relatively, and difference has the significance meaning.
The double cold-damp syndrome of suffering from a deficiency of the kidney: treatment group clinical cure rate is 13.5%, and obvious effective rate is 48.6%, and effective percentage is 28.4%, and clinical cure and obvious effective rate are 62.1%, and total effective rate is 90.5%; The matched group clinical cure rate is 9.1%, and obvious effective rate is 36.4%, and effective percentage is 31.8%, and clinical cure and obvious effective rate are 45.5%, and total effective rate is 77.3%.Two groups relatively, and difference does not have the significance meaning.
4, two groups of different lumbago severity extent curative effects relatively
The table 34 liang different lumbago severity extent curative effects of group are (rank test) relatively
Group example number recovery from illness (%) produce effects (%) is (%) invalid (%) u P effectively
Treatment organizes 44 17 8 10 9 0.68 0.41
Slight (38.6) (18.2) (22.7) (20.5)
Matched group 21 4683
(19)????????(28.6)??????(38.1)??????(14.3)
Treatment organizes 191 25 93 66 7 3.26 0.0011
Moderate (13.1) (48.7) (34.6) (3.7)
Matched group 67 3 24 35 5
(4.5)???????(35.8)??????(52.2)??????(7.5)
Treatment organizes 76 9 49 12 6 1.41 0.162
Severe (11.8) (64.5) (15.8) (7.9)
Matched group 12 0750
(0.0)???????(58.3)??????(41.7)??????(0.0)
The treatment group of severity extent moderate and matched group patient curative effect compare, and difference has the significance meaning.Treatment group that severity extent is slight and matched group patient curative effect compare, and difference does not have the significance meaning.The treatment group of severity extent severe and matched group patient curative effect compare, and difference does not have the significance meaning.
5, treatment back muscular soreness improvement degree relatively
Table 35 treatment back muscular soreness improvement degree relatively
*
Group example number increases the weight of not have 1 grade of improvement of improvement and improves 3 grades for 2 grades
Treatment organizes 300 0 27 164 91 18
Matched group 97 0 16 56 23 2
Rank test u=2.51 P=0.0122
*Increase the weight of expression: increase the weight of before the treatment treatment back
Improve 1 grade of expression: the treatment back reduces by 1 grade before the treatment
Improve 2 grades of expressions: the treatment back reduces by 2 grades before the treatment
Improve 3 grades of expressions: the treatment back reduces by 3 grades before the treatment
Two groups of treatment back muscular soreness improvement degree compare, and difference has the significance meaning.
6, treatment back joint stuffiness improvement degree relatively
Table 36 treatment back joint stuffiness improvement degree relatively
*
Group example number increases the weight of not have 1 grade of improvement of improvement and improves 3 grades for 2 grades
Treatment organizes 289 0 34 165 73 17
Matched group 93 0 19 57 16 1
Rank test u=2.95 P=0.0032
*Increase the weight of expression: increase the weight of before the treatment treatment back
Improve 1 grade of expression: the treatment back reduces by 1 grade before the treatment
Improve 2 grades of expressions: the treatment back reduces by 2 grades before the treatment
Improve 3 grades of expressions: the treatment back reduces by 3 grades before the treatment
Two groups of treatment back joint stuffiness improvement degree compare, and difference has the significance meaning.
7, treatment back lumbar part movable function curative effect relatively
The anteflexion function curative effect of table 37 treatment back lumbar part relatively
*
Group example number increases the weight of not have improvement and improves 2 grades for 1 grade
Treatment organizes 266 0 52 180 34
Matched group 85 0 31 49 5
Rank test u=3.35 P=0.0008
*Increase the weight of: treatment is preceding poor to refer to treat the anteflexion function of back lumbar part;
No change: refer to treat the anteflexion function of front waist＜90 °; Do not improve yet after the treatment;
Improve 1 grade: refer to treat the anteflexion function of back lumbar part and be improved as 70 °-90 ° by≤70 °, or by 70 °-90 ° be improved as 〉=90 °, promptly recover normal;
Improve 2 grades: refer to treat the anteflexion function of back lumbar part by≤70 ° be improved as 〉=90 °, promptly recover normal.
Two groups of anteflexion function curative effects of treatment back lumbar part compare, and difference has the significance meaning.
Table 38 treatment back lumbar part layback function curative effect relatively
*
Group example number increases the weight of not have improvement and improves 2 grades for 1 grade
Treatment organizes 254 0 65 166 23
Matched group 75 0 28 45 2
Rank test u=2.405 P=0.016
*Increase the weight of: treatment is preceding poor to refer to treat back lumbar part layback function;
No change: refer to treat front waist layback function＜30 °; Do not improve yet after the treatment;
Improve 1 grade: refer to treat back lumbar part layback function and be improved as 10 °-30 ° by≤10 °, or by 10 °-30 ° be improved as 〉=30 °, promptly recover normal;
Improve 2 grades: refer to treat back lumbar part layback function by≤10 ° be improved as 〉=30 °, promptly recover normal.
Two groups of treatment back lumbar part layback function curative effects compare, and difference has the significance meaning.
The function curative effect is bent relatively in table 39 treatment back lumbar part left side
*
Group example number increases the weight of not have 1 grade of improvement
Treatment organizes 155 0 44 111
Matched group 48 0 22 26
Rank test u=2.25 P=0.024
*Increase the weight of: refer to treat the back lumbar part left side and bend function than poor before treating;
No change: refer to treat front waist left side and bend function＜20 °; Do not improve yet after the treatment;
Improve 1 grade: refer to treat back lumbar part left side bend function by＜20 ° be improved as 〉=20 °, promptly recover normal;
The function curative effect is bent relatively in two groups of treatment back lumbar part left sides, and difference has the significance meaning.
The function curative effect is bent relatively in table 40 treatment back lumbar part right side
*
Group example number increases the weight of not have 1 grade of improvement
Treatment organizes 133 0 36 97
Matched group 48 0 21 27
Rank test u=2.13 P=0.033
*Increase the weight of: refer to treat the back lumbar part right side and bend function than poor before treating;
No change: refer to treat the front waist right side and bend function＜20 °; Do not improve yet after the treatment;
Improve 1 grade: refer to treat the back lumbar part right side bend function by＜20 ° be improved as 〉=20 °, promptly recover normal;
The function curative effect is bent relatively in two groups of treatment back lumbar part right sides, and difference has the significance meaning.
8, treatment back cardinal symptom disappearance rate relatively
Table 41 treatment back cardinal symptom disappearance rate is (one) relatively
The aching and limp unable hands and feet being not warm of group lumbago muscular soreness joint stuffiness knee
Control original example several 311 300 289 255 95
Treat the example several 124 180 185 181 66 that disappears
Group disappearance rate % 39.87 60.0 64.01 70.98 69.47
To original example several 100 97 93 79 27
According to the example several 39 48 46 57 14 that disappears
Group disappearance rate % 39.0 49.48 49.46 72.15 51.85
X
2?????????0.02?????????3.32????????6.23??????????0.04??????????????2.89
P???????????0.88?????????0.07????????0.013?????????0.84??????????????0.09
Table 42 treatment back cardinal symptom disappearance rate is (two) relatively
Group frequent micturition, the frequent urination at night dribble of urine premature ejaculation hyposexuality of passing out semen not to the utmost
Control original example several 180 43 15 17 62
Treat the example several 111 23 10 11 21 that disappears
Group disappearance rate % 61.67 53.49 66.67 64.71 33.87
To original example several 57 833 20
According to the example several 31 3337 that disappears
Group disappearance rate % 54.39 37.5 100 100 35.0
X
20.96 the accurate accurate probabilistic method 0.01 of the accurate probabilistic method of probabilistic method
P???????????0.33?????????????0.47??????????????0.52??????????0.52?????????0.93
Two groups of treatment back cardinal symptom disappearance rate are relatively: remove joint stuffiness, two groups of comparing differences have outside the significance meaning, the disappearance rate of two groups of other symptoms of treatment back relatively, difference there are no significant meaning.
9, follow up a case by regular visits to situation relatively
Follow up a case by regular visits to after 2 weeks of case drug withdrawal to clinical cure, treatment group clinical cure 51 examples have been followed up a case by regular visits to 43 examples, and efficacy determination is clinical recovery 39 examples as a result, produce effects 4 examples, cure rate 90.7%, obvious effective rate 9.3%; Treatment group clinical cure 7 examples have been followed up a case by regular visits to 6 examples, and efficacy determination all still is a clinical recovery.
Five, safety detects
Detected 185 routine routine blood tests before the treatment of treatment group, wherein 176 routine leukocyte counts are in normal range, and 2 routine leukocyte counts are lower than 4.0 * 10
9/ L, 7 routine leukocyte counts surpass 10.0 * 10
9/ L.
The normal person of 176 example treatment proleukocyte numbers has checked 154 examples after the treatment, have 4 routine leukocyte counts to surpass 10.0 * 10
9/ L (is respectively 13.3 * 10
9/ L, 16.9 * 10
9/ L, 10.1 * 10
9/ L and 11.2 * 10
9/ L), all the other are all in normal range;
2 example treatment proleukocyte numbers are lower than 4.0 * 10
9/ L person, the check of treatment back all recovers normal;
7 example treatment proleukocyte numbers surpass 10.0 * 10
9/ L person, the check of treatment back wherein has 5 routine leukocyte counts to recover normal, has 2 examples not check.
Detected 162 routine routine urinalysis before the treatment group treatment, wherein 145 examples be normal, 17 routine unusually (mainly be leukocyte, erythrocyte, albumen +～+++).Normal person before the 145 example treatments has checked 124 examples after the treatment, wherein 123 examples are still normal, 1 example unusual (Ery25/ul).Unusual person before the 17 example treatments has checked 16 examples after the treatment, 12 examples recover normal, and 4 examples are still unusual, and 1 example is not checked.
Do not check that the treatment back is checked to normal before the 1 example treatment.
Detected 152 routine stool routine examinations before the treatment of treatment group, 151 examples are normal, and 1 example is unusual.Normal person before the 151 example treatments has checked 126 examples after the treatment, all still be normal.Unusual person before the 1 example treatment, not check after the treatment.
Detected 155 routine liver functions (GPT) before the treatment of treatment group, wherein 147 examples are in normal range, and 8 examples are higher than normal value.Normal person before the 147 example treatments has checked 128 examples after the treatment, wherein 125 examples are still in normal range, and 3 examples are higher than normal value (GPT is 57u/L, 45u/L, 51u/L).Be higher than normal value person before the 8 example treatments, the check of treatment back, 2 recover normal, and 3 examples are unusual (44u/L, 46u/L, 42u/L) still, and 3 examples are not checked.
Detected 171 routine renal functioies (BUN) before the treatment of treatment group, wherein 167 examples are in normal range, and 4 examples are higher than normal value.Normal person before the 167 routine treatments has checked 143 examples after the treatment, 138 examples are in normal range, and 5 examples are (7.2mmol/L, 7.6mmol/L, 7.3mmol/L, 7.3mmol/L, 7.2mmol/L) unusually.Be higher than normal value person before the 4 example treatments, the check of treatment back recovers normal.
Detected 137 routine electrocardiograms before the treatment of treatment group, wherein 106 examples are normal ECG, and 31 examples are abnormal electrocardiographic pattern; Normal ECG person before the 106 example treatments has checked 84 examples after the treatment, 82 examples still are normal ECG, and 2 examples are unusual, and (1 example is a sinus bradycardia, heart rate 58 times/minute; 1 example is accidental stopping up property premature beat).Before the 31 example treatments is the abnormal electrocardiographic pattern person, has checked 14 examples after the treatment and has recovered normal, and 12 examples still are unusual, and 5 examples are not checked.
Detected 50 routine routine blood tests before the treatment of control group, wherein 46 routine leukocyte counts are in normal range, and 4 routine leukocyte counts surpass 10.0 * 10
9/ L.
The normal person of 46 example treatment proleukocyte numbers has checked 43 examples after the treatment, 40 examples are arranged still in normal range, and 3 routine leukocyte counts surpass 10.0 * 10
9/ L (is 10.1 * 10
9/ L, 13.3 * 10
9/ L, 16.1 * 10
9/ L).
4 example treatment proleukocyte numbers surpass 10.0 * 10
9/ L person, it is normal that the check of treatment back all recovers.
Detected 42 routine routine urinalysis before the treatment of control group, wherein 35 examples are normal, 7 examples unusual (mainly be leukocyte, erythrocyte +～+++).Normal person before the 35 example treatments has checked 32 examples after the treatment, wherein 31 examples are still normal, 1 example unusual (Ery150/ul).Unusual person before the 7 example treatments, the check of treatment back, 3 examples recover normal, and 4 examples are still unusual.
Detected 40 routine stool routine examinations before the treatment of control group, be normal.Checked 33 examples after the treatment, all still normal.
Do not check that the treatment back is checked to normal before the 1 example treatment.
Detected 40 routine liver functions (GPT) before the treatment of control group, 39 examples are in normal range, and 1 example is unusual.34 examples have been checked after the treatment, all still in normal range.Unusual before the 1 example treatment, the check of treatment back is unusual (GPT is 57u/L) still.
Detected 47 routine renal functioies (BUN) before the treatment of control group, wherein 46 examples are in normal range, and 1 example is higher than normal value.Normal person before the 46 example treatments has checked 41 examples, all still in normal range after the treatment.Be higher than normal value person before the 1 example treatment, not check after the treatment.
Detected 39 routine electrocardiograms before the treatment of control group, 25 examples are normal ECG, and 14 examples are abnormal electrocardiographic pattern.Before the 25 example treatments is the normal ECG person, has checked 21 examples after the treatment, still is normal ECG.Before the 14 example treatments is the abnormal electrocardiographic pattern person, the check of treatment back, and 6 examples recover normal, and 6 examples still are unusual, and 2 examples are not checked.
Six, untoward reaction is observed
10 routine patient's untoward reaction symptoms are arranged after the medication of treatment group, account for 3.0% (10/338, comprise and reject case):
Occur slight erythra (time of occurrence does not write down) after the 1 routine medication, continue 2 days, disappear, do not stop investigational agent in the test with the oral processing of hismanal 6mg back erythra;
Slight erythra occurred on the 1st day after the 1 routine medication, continue 2 days, do not write down the order of severity of erythra, do not take treatment measures, the investigational agent erythra disappearance after 2 days of stopping using;
Slight erythra occurs on the 1st day after the 1 routine medication, continue 3 days, take treatment measures not quite clear, do not stop investigational agent in the test;
Slight erythra occurred on the 2nd day after the 1 routine medication, continue 1 day, the order of severity of erythra is general, puts processing outward on the skin with PIYANPINGSHUANG, does not stop investigational agent in the test;
Slight erythra occurs on the 3rd day after the 1 routine medication, continue 2 days, do not take treatment measures, do not stop investigational agent in the test;
Slight erythra occurs on the 3rd day after the 1 routine medication, continue 3 days, do not take treatment measures, do not stop investigational agent in the test.
Slight erythra occurred on the 4th day after the 1 routine medication, continue 2 days, put processing outward on the skin, drug withdrawal erythra disappearance after 2 days in the test with PIYANPINGSHUANG;
Slight erythra occurs on the 5th day after the 1 routine medication, continue 3 days, do not take treatment measures, do not stop investigational agent in the test;
Slight erythra occurs on the 6th day after the 1 routine medication, continue 3 days, do not take treatment measures, do not stop investigational agent in the test;
Slight erythra occurs on the 18th day after the 1 routine medication, continue 6 days.Put processing back erythra outward on the skin with PIYANPINGSHUANG and disappear not drug withdrawal in the test;
Local erythra appears in 2 routine patients after the matched group medication, accounts for 1.90% (2/105, comprise and reject case):
Occur local erythra after the 1 routine medication after the 15th day, continue 2 days, do not write down the order of severity of erythra, do not take treatment measures, not drug withdrawal in the process of the test.
Slight erythra occurred on the 6th day after the 1 routine medication, continue 3 days, PIYANPINGSHUANG is put processing outward on the skin, and drug withdrawal is the erythra disappearance after 3 days.
Seven, result of the test:
This test has qualified experimenter's 411 examples, and 311 examples (chronic lumbar muscle strain 132 examples, lumbar vertebra hyperosteogeny disease 179 examples) are organized in treatment, matched group 100 examples (chronic lumbar muscle strain 40 examples, lumbar vertebra hyperosteogeny disease 60 examples).Treatment group Chinese medical discrimination is nephrasthenia syndrome 237 examples, cold-damp syndrome 74 examples of holding concurrently of suffering from a deficiency of the kidney; The matched group Chinese medical discrimination is nephrasthenia syndrome 78 examples, cold-damp syndrome 22 examples of holding concurrently of suffering from a deficiency of the kidney.Treatment group inpatient 41 examples, matched group inpatient 9 examples, all the other are the outpatient.Total case 32 examples of rejecting, 27 examples are organized in treatment, matched group 5 examples.
Comparability detects and shows before the treatment, except that treatment group lumbago degree overweights matched group, the treatment group course of disease is longer than the matched group, comparisons such as sick kinds of age, sex, tcm syndrome, doctor trained in Western medicine, lumbago character, muscular soreness, joint stuffiness, waist movable function, other clinical symptoms and picture of the tongue, pulse condition before two groups of treatments, difference there are no significant meaning.The principal element that prompting influences two groups of prognosis has harmony.
Total effects is the result show, treatment group clinical cure rate is 16.4%, and obvious effective rate is 48.2%, and effective percentage is 28.3%, and clinical cure and obvious effective rate are 64.6%, and total effective rate is 92.9%; The matched group clinical cure rate is 7.0%, and obvious effective rate is 37.0%, and effective percentage is 48.0%, and clinical cure and obvious effective rate are 44.0%, and total effective rate is 92.0%.Two groups relatively, and difference has the significance meaning.Prompting waist kidney cream treatment lumbago due to renal deficiency has clinical efficacy preferably, is better than contrasting medicine.
The different sick efficacy results of planting show that treatment group treatment chronic lumbar muscle strain patient clinical cure rate is 21.2%, and obvious effective rate is 45.5%, and effective percentage is 28.0%, and clinical cure and obvious effective rate are 66.7%, and total effective rate is 94.7%; The matched group clinical cure rate is 10.0%, and obvious effective rate is 47.5%, and effective percentage is 40.0%, and clinical cure and obvious effective rate are 57.5%, and total effective rate is 97.5%.Two groups relatively, and difference does not have the significance meaning; Treatment group treatment lumbar vertebra hyperosteogeny disease patient clinical cure rate is 12.8%, and obvious effective rate is 50.3%, and effective percentage is 28.5%, and clinical cure and obvious effective rate are 63.1%, and total effective rate is 91.6%; The matched group clinical cure rate is 5.0%, and obvious effective rate is 30.0%, and effective percentage is 53.3%, and clinical cure and obvious effective rate are 35.0%, and total effective rate is 88.3%.Two groups relatively, and difference has the significance meaning.Point out medicine composite for curing chronic lumbar muscle strain clinical efficacy of the present invention to be better than matched group, treatment lumbar vertebra hyperosteogeny disease curative effect is similar to matched group.
The tcm syndrome curative effect shows that nephrasthenia syndrome treatment group clinical cure rate is 17.3%, and obvious effective rate is 48.1%, and effective percentage is 28.3%, and clinical cure and obvious effective rate are 65.4%, and total effective rate is 93.7%; The matched group clinical cure rate is 6.4%, and obvious effective rate is 37.2%, and effective percentage is 52.6%, and clinical cure and obvious effective rate are 43.6%, and total effective rate is 96.2%.Two groups relatively, and difference has the significance meaning.The double cold-damp syndrome treatment group clinical cure rate of suffering from a deficiency of the kidney is 13.5%, and obvious effective rate is 48.6%, and effective percentage is 28.4%, and clinical cure and obvious effective rate are 62.1%, and total effective rate is 90.5%; The matched group clinical cure rate is 9.1%, and obvious effective rate is 36.4%, and effective percentage is 31.8%, and clinical cure and obvious effective rate are 45.5%, and total effective rate is 77.3%.Two groups relatively, and difference does not have the significance meaning.Point out medicine composite for curing nephrasthenia syndrome lumbago clinical efficacy of the present invention to be better than matched group, the suffer from a deficiency of the kidney cold-damp syndrome lumbago curative effect of holding concurrently of treatment is similar to matched group.
Different severity extent patient efficacy results show that pharmaceutical composition of the present invention is better than contrasting medicine (P＜0.05) for patient's curative effect of moderate severity extent, and two groups of clinical efficacies slight, severe patient compare, and difference does not have the significance meaning.This may be slight with two groups, severe patient's case load is less relevant.
Clinical symptoms, sign efficacy result show that clinical symptoms, signs such as two groups of treatment back patients' lumbago, muscular soreness, joint stuffiness, waist movable function all have clear improvement, and two groups of comparing differences have the significance meaning, and the treatment group is better than matched group.Point out medicine composite for curing nephrasthenia syndrome lumbago of the present invention that clinical efficacy is preferably arranged, can obviously improve patient's clinical symptoms, sign, curative effect is better than matched group.
The safety testing result shows, the treatment group has before the 3 routine liver functions treatments normal, and that the check of treatment back is higher than is normal (GPT be respectively 45,51,57u/L); The treatment group has before the 5 routine renal function curings normal, and that the check of treatment back is higher than is normal (BUN be respectively 7.2,7.2,7.3,7.3,7.6mmol/L).All a little higher than range of normal value, in the critical range of its normal value, owing to fail further above-mentioned patient to be followed the trail of inspection, the relation with clear and definite and trial drug medication still is difficult to definitely be judged as due to the trial drug.
It is normal that the treatment group has 4 examples, matched group to have before the treatment of 3 routine leukocyte, and the check of treatment back is higher than that normal (treatment is organized 4 routine leukocyte counts and is respectively 10.1,11.2,13.3,16.9 * 10
9/ L, matched group 3 examples are respectively 10.1,13.3,16.1 * 10
9/ L); 1 example is organized in treatment, matched group 1 routine routine urinalysis treatment is preceding normal, and the check of treatment back is [1 example (Ery25/ul) is organized in treatment, matched group 1 example (Ery150/ul)] unusually.Owing to fail further above-mentioned patient to be followed the trail of inspection, the relation with clear and definite and trial drug medication still is difficult to definitely be judged as due to the trial drug.
It is preceding normal that 2 routine electrocardiogram treatments are organized in treatment, and check 1 example in treatment back is a sinus bradycardia, heart rate 58 times/minute; 1 example is accidental stopping up property premature beat.This abnormal change also is common in middle-aged and elderly people, still is difficult to definitely be judged as due to the trial drug.
Untoward reaction is observed and is shown all have the part patient symptoms such as local erythra to occur after two groups of medications.The treatment group has 10 examples (accounting for 3.0%), and 3 examples are transference cure after using the PIYANPINGSHUANG processing; 2 routine drug withdrawals transference cure after 2 days continues medication, and any treatment measures are not taked in all not drug withdrawals.Matched group has 2 examples (accounting for 1.90%), and 1 example is handled through using PIYANPINGSHUANG, and drug withdrawal is transference cure after 3 days; Any measure is not taked in the not drug withdrawal of 1 example.
The clinical observation on the therapeutic effect conclusion: this is tested the single at random blind controlled trial result of 411 examples and shows, medicine composite for curing lumbago due to renal deficiency of the present invention has clinical efficacy preferably, clinical symptoms and the curative effect that can obviously improve the patient are better than contrasting medicine, the clinical treatment that can be used for the lumbago due to renal deficiency patient, clinical drug safety.
Claims (13)
1, a kind of pharmaceutical composition that is used for the treatment of lumbago due to renal deficiency, it is characterized in that: it mainly is made up of following raw medicaments in portion by weight:
9～87 parts of 9～87 parts of Radix Rehmanniae Preparata of 9～87 parts of Fructus Anisi Stellatis of Herba Cistanches
9～87 parts of 9～87 parts of Fructus Cnidiis of 9～87 parts of Herba Epimedii of Fructus Psoraleae
9～87 parts in 9～87 portions of Radix Glycyrrhizaes of 9～87 parts of Radix Dipsacis of Radix Achyranthis Bidentatae
9～87 parts of 9～87 parts of Fructus Lycii of 9～87 parts of Semen Cuscutae of the Cortex Eucommiae
6～57 parts of 9～87 parts of Radix Aconiti Lateralis Preparatas of 9～87 parts of Fructus Foeniculi of Semen Plantaginis
6～57 parts of 3～30 parts of Myrrhas of 6～57 parts of Olibanums of Fructus Schisandrae Chinensis
6～60 parts of 1～13 part of Camphoras of 6～57 parts of Herba Cynomoriis of Flos Caryophylli
1～11 part of 5～50 parts of Oleum Cinnamomi of 4～39 portions of Oleum menthae of Borneolum Syntheticum
11～103 parts of 11～99 parts of Resina Liquidambaris thick pastes of methyl salicylate
2, according to the described pharmaceutical composition of claim 1, it is characterized in that: described ingredients weight parts ratio range is:
14～58 parts of 14～58 parts of Radix Rehmanniae Preparata of 14～58 parts of Fructus Anisi Stellatis of Herba Cistanches
14～58 parts of 14～58 parts of Fructus Cnidiis of 14～58 parts of Herba Epimedii of Fructus Psoraleae
14～58 parts in 14～58 portions of Radix Glycyrrhizaes of 14～58 parts of Radix Dipsacis of Radix Achyranthis Bidentatae
14～58 parts of 14～58 parts of Fructus Lycii of 14～58 parts of Semen Cuscutae of the Cortex Eucommiae
9～38 parts of 14～58 parts of Radix Aconiti Lateralis Preparatas of 14～58 parts of Fructus Foeniculi of Semen Plantaginis
5～20 parts of 5～20 parts of Myrrhas of 9～38 parts of Olibanums of Fructus Schisandrae Chinensis
10～40 parts of 2～9 parts of Camphoras of 5～20 parts of Herba Cynomoriis of Flos Caryophylli
1～7 part of 8～33 parts of Oleum Cinnamomi of 6～20 portions of Oleum menthae of Borneolum Syntheticum
17～69 parts of 16～66 parts of Resina Liquidambaris thick pastes of methyl salicylate
3, according to the described pharmaceutical composition of claim 2, it is characterized in that: described composition weight umber is:
30 parts of 30 parts of Radix Rehmanniae Preparata of 30 parts of Fructus Anisi Stellatis of Herba Cistanches
30 parts of 30 parts of Fructus Cnidiis of 30 parts of Herba Epimedii of Fructus Psoraleae
30 parts in 30 portions of Radix Glycyrrhizaes of 30 parts of Radix Dipsacis of Radix Achyranthis Bidentatae
30 parts of 30 parts of Fructus Lycii of 30 parts of Semen Cuscutae of the Cortex Eucommiae
20 parts of 30 parts of Radix Aconiti Lateralis Preparatas of 30 parts of Fructus Foeniculi of Semen Plantaginis
10 parts of 10 parts of Myrrhas of 20 parts of Olibanums of Fructus Schisandrae Chinensis
21 parts of 5 parts of Camphoras of 10 parts of Herba Cynomoriis of Flos Caryophylli
4 parts of 18 parts of Oleum Cinnamomi of 14 portions of Oleum menthae of Borneolum Syntheticum
36 parts of 34 parts of Resina Liquidambaris thick pastes of methyl salicylate
4, the arbitrary described preparation of drug combination method of a kind of preparation claim 1～3 comprises the following steps:
(1) take by weighing each component by following weight portion:
9～87 parts of 9～87 parts of Radix Rehmanniae Preparata of 9～87 parts of Fructus Anisi Stellatis of Herba Cistanches
9～87 parts of 9～87 parts of Fructus Cnidiis of 9～87 parts of Herba Epimedii of Fructus Psoraleae
9～87 parts in 9～87 portions of Radix Glycyrrhizaes of 9～87 parts of Radix Dipsacis of Radix Achyranthis Bidentatae
9～87 parts of 9～87 parts of Fructus Lycii of 9～87 parts of Semen Cuscutae of the Cortex Eucommiae
6～57 parts of 9～87 parts of Radix Aconiti Lateralis Preparatas of 9～87 parts of Fructus Foeniculi of Semen Plantaginis
6～57 parts of 3～30 parts of Myrrhas of 6～57 parts of Olibanums of Fructus Schisandrae Chinensis
6～60 parts of 1～13 part of Camphoras of 6～57 parts of Herba Cynomoriis of Flos Caryophylli
1～11 part of 5～50 parts of Oleum Cinnamomi of 4～39 portions of Oleum menthae of Borneolum Syntheticum
11～103 parts of 11～99 parts of Resina Liquidambaris thick pastes of methyl salicylate
(2) Flos Caryophylli, Fructus Anisi Stellati are extracted volatile oil respectively, the volatile oil of gained is standby; Fructus Anisi Stellati and Flos Caryophylli residue behind the extraction volatile oil are mixed with Herba Cistanches, Radix Rehmanniae Preparata, Fructus Psoraleae, Herba Epimedii, Fructus Cnidii, Radix Achyranthis Bidentatae, Radix Dipsaci, Radix Glycyrrhizae, the Cortex Eucommiae, Semen Cuscutae, Fructus Lycii, Semen Plantaginis, Fructus Foeniculi, Radix Aconiti Lateralis Preparata, Fructus Schisandrae Chinensis, Olibanum, Myrrha, Herba Cynomorii, added alcohol reflux 2 hours, extracting solution is condensed into thick paste.
(3) volatile oil of Camphora, Borneolum Syntheticum, Oleum menthae, Oleum Cinnamomi, methyl salicylate and step (2) gained is mixed together after, mix with the prepared thick paste of Resina Liquidambaris thick paste and step (2) again, make the preparation intermediate, make preparation through preparations shaping technology again, promptly.
5, according to the described pharmaceutical composition of claim 1, it is characterized in that: wherein crude drug can also have the diphhydramine hydrochloride of 2～23 weight portions.
6, according to the described pharmaceutical composition of claim 5, wherein the consumption of a crude drug is:
14～58 parts of 14～58 parts of Radix Rehmanniae Preparata of 14～58 parts of Fructus Anisi Stellatis of Herba Cistanches
14～58 parts of 14～58 parts of Fructus Cnidiis of 14～58 parts of Herba Epimedii of Fructus Psoraleae
14～58 parts in 14～58 portions of Radix Glycyrrhizaes of 14～58 parts of Radix Dipsacis of Radix Achyranthis Bidentatae
14～58 parts of 14～58 parts of Fructus Lycii of 14～58 parts of Semen Cuscutae of the Cortex Eucommiae
9～38 parts of 14～58 parts of Radix Aconiti Lateralis Preparatas of 14～58 parts of Fructus Foeniculi of Semen Plantaginis
5～20 parts of 5～20 parts of Myrrhas of 9～38 parts of Olibanums of Fructus Schisandrae Chinensis
10～40 parts of 2～9 parts of Camphoras of 5～20 parts of Herba Cynomoriis of Flos Caryophylli
1～7 part of 8～33 parts of Oleum Cinnamomi of 6～20 portions of Oleum menthae of Borneolum Syntheticum
3～15 parts of 17～69 parts of diphhydramine hydrochlorides of 16～66 parts of Resina Liquidambaris thick pastes of methyl salicylate
7, according to the described pharmaceutical composition of claim 6, wherein the consumption of a crude drug is:
30 parts of 30 parts of Radix Rehmanniae Preparata of 30 parts of Fructus Anisi Stellatis of Herba Cistanches
30 parts of 30 parts of Fructus Cnidiis of 30 parts of Herba Epimedii of Fructus Psoraleae
30 parts in 30 portions of Radix Glycyrrhizaes of 30 parts of Radix Dipsacis of Radix Achyranthis Bidentatae
30 parts of 30 parts of Fructus Lycii of 30 parts of Semen Cuscutae of the Cortex Eucommiae
20 parts of 30 parts of Radix Aconiti Lateralis Preparatas of 30 parts of Fructus Foeniculi of Semen Plantaginis
10 parts of 10 parts of Myrrhas of 20 parts of Olibanums of Fructus Schisandrae Chinensis
21 parts of 5 parts of Camphoras of 10 parts of Herba Cynomoriis of Flos Caryophylli
4 parts of 18 parts of Oleum Cinnamomi of 14 portions of Oleum menthae of Borneolum Syntheticum
8 parts of 36 parts of diphhydramine hydrochlorides of 34 parts of Resina Liquidambaris thick pastes of methyl salicylate
8, any described preparation of drug combination method of claim 5～7 comprises the following steps:
(1) take by weighing each component by following weight portion:
9～87 parts of 9～87 parts of Radix Rehmanniae Preparata of 9～87 parts of Fructus Anisi Stellatis of Herba Cistanches
9～87 parts of 9～87 parts of Fructus Cnidiis of 9～87 parts of Herba Epimedii of Fructus Psoraleae
9～87 parts in 9～87 portions of Radix Glycyrrhizaes of 9～87 parts of Radix Dipsacis of Radix Achyranthis Bidentatae
9～87 parts of 9～87 parts of Fructus Lycii of 9～87 parts of Semen Cuscutae of the Cortex Eucommiae
6～57 parts of 9～87 parts of Radix Aconiti Lateralis Preparatas of 9～87 parts of Fructus Foeniculi of Semen Plantaginis
6～57 parts of 3～30 parts of Myrrhas of 6～57 parts of Olibanums of Fructus Schisandrae Chinensis
6～60 parts of 1～13 part of Camphoras of 6～57 parts of Herba Cynomoriis of Flos Caryophylli
1～11 part of 5～50 parts of Oleum Cinnamomi of 4～39 portions of Oleum menthae of Borneolum Syntheticum
2～23 parts of 11～103 parts of diphhydramine hydrochlorides of 11～99 parts of Resina Liquidambaris thick pastes of methyl salicylate
(2) Flos Caryophylli, Fructus Anisi Stellati are extracted volatile oil respectively, the volatile oil of gained is standby; Fructus Anisi Stellati and Flos Caryophylli residue behind the extraction volatile oil are mixed with Herba Cistanches, Radix Rehmanniae Preparata, Fructus Psoraleae, Herba Epimedii, Fructus Cnidii, Radix Achyranthis Bidentatae, Radix Dipsaci, Radix Glycyrrhizae, the Cortex Eucommiae, Semen Cuscutae, Fructus Lycii, Semen Plantaginis, Fructus Foeniculi, Radix Aconiti Lateralis Preparata, Fructus Schisandrae Chinensis, Olibanum, Myrrha, Herba Cynomorii, added alcohol reflux 2 hours, extracting solution is condensed into thick paste.
(3) after the volatile oil that Camphora, Borneolum Syntheticum, Oleum menthae, Oleum Cinnamomi, methyl salicylate and step (2) are extracted is mixed together, mix with the prepared thick paste of Resina Liquidambaris thick paste, diphhydramine hydrochloride and step (2) again, make the preparation intermediate, make preparation through preparations shaping technology again, promptly.
9, according to claim 1,2,3,5,6 or 7 described any pharmaceutical compositions, it is characterized in that and to make any acceptable clinically suitable formulations by this area conventional method.
10, according to the described pharmaceutical composition of claim 9, it is characterized in that: described pharmaceutical preparation is tablet, capsule, granule, powder, pill, oral liquid, syrup, drop pill, ointment, nasal formulations, aerosol or spray, plaster, emplastrum.
11, according to the described pharmaceutical composition of claim 10, it is characterized in that: described pharmaceutical preparation is emplastrum.
12, claim 1,2,3,5, the purposes of 6 or 7 described any pharmaceutical compositions in preparation treatment lumbago due to renal deficiency medicine.
13, claim 1,2,3,5, the purposes of 6 or 7 described any pharmaceutical compositions in preparation treatment urgent micturition, frequent micturition medicine.
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| RU2553625C2 (en) * | 2013-10-02 | 2015-06-20 | Дмитрий Александрович Никифоров | Ester-oil composition 'bioprotection' for treating asthenic syndrome in patients with dyscirculatory encephalopathy |
| CN105168614A (en) * | 2015-09-08 | 2015-12-23 | 张洲玲 | Traditional Chinese medicine for tonifying kidney and strengthening bones and preparation method of traditional Chinese medicine |
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| CN105943624A (en) * | 2016-06-29 | 2016-09-21 | 王树华 | Medicine for treating nephritis and hydronephrosis and preparation method thereof |
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| CN1236043C (en) * | 2002-12-31 | 2006-01-11 | 张戈平 | Supplemental strengthening wine and preparing process thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| RU2553625C2 (en) * | 2013-10-02 | 2015-06-20 | Дмитрий Александрович Никифоров | Ester-oil composition 'bioprotection' for treating asthenic syndrome in patients with dyscirculatory encephalopathy |
| CN105456395A (en) * | 2014-06-03 | 2016-04-06 | 长沙市博泰生物科技有限公司 | Method for preparing wet wipes for sexual lives |
| CN105168614A (en) * | 2015-09-08 | 2015-12-23 | 张洲玲 | Traditional Chinese medicine for tonifying kidney and strengthening bones and preparation method of traditional Chinese medicine |
| CN105943624A (en) * | 2016-06-29 | 2016-09-21 | 王树华 | Medicine for treating nephritis and hydronephrosis and preparation method thereof |
| CN110824055A (en) * | 2019-11-21 | 2020-02-21 | 国药集团德众（佛山）药业有限公司 | Establishing method of waist and kidney paste fingerprint and waist and kidney paste comparison fingerprint |
| CN110824055B (en) * | 2019-11-21 | 2022-03-08 | 国药集团德众（佛山）药业有限公司 | Establishing method of waist and kidney paste fingerprint and waist and kidney paste comparison fingerprint |
| CN111437312A (en) * | 2020-04-08 | 2020-07-24 | 刘佳 | Formula of natural compound essential oil for improving reproductive system |
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| CN1323692C (en) | 2007-07-04 |
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