CN103432497B - External preparation for treating haemorrhoids - Google Patents
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Abstract
The invention discloses an external preparation for treating haemorrhoids. The external preparation comprises active ingredients and auxiliary materials acceptable in pharmaceutical science, wherein the active ingredients are prepared through water extract and alcohol precipitate by the following traditional Chinese medicinal materials in parts by weight: 8-13 parts of sanguisorba officinalis, 8-13 parts of honeysuckle, 8-13 parts of radix stemonae, 10-18 parts of ligusticum wallichii, 10-18 parts of sophora flower, 10-18 parts of agrimonia pilosa, 10-18 parts of purslane, 25-35 parts of burdock, and 25-35 parts of cortex dictamni. Through combined actions of stopping blood, improving microcirculation, diminishing inflammation and easing pain, the external preparation can treat the haemorrhoids once and for all.
Description
Technical field
The invention belongs to medical art, relate to a kind of pharmaceutical composition for the treatment of hemorrhoid, particularly relate to a kind of external preparation for the treatment of hemorrhoid.
Background technology
Hemorrhoid are a kind of common property, multiple characteristic of disease anal and intestinal disease, hemorrhoid are under rectum end mucosa and under anal canal skin, the soft vein agglomerate expanded and flexing is formed occurs venous plexus, main clinical manifestation for having blood in stool, pain, edema, falling inflation, pruritus, secretions increase and the symptom such as to deviate from, relevant research shows, the sickness rate of China's hemorrhoid is about 46%, reach 70% in some district, sickness rate that is American-European, Japan Data investigation is about 40%-60%.Having blood in stool, deviating from and the symptoms such as pain appears because of hemorrhoid in many patients, has had a strong impact on life, working and learning, so there is the exploitation of the hemorrhoid treating medicine of good result to have great importance.
The method of current treatment hemorrhoid mainly contains Drug therapy, surgical ligation and injection treatment.Anorectal educational circles of China has held the sick symposium of national hemorrhoid in April, 2000 in Chengdu, to explicitly pointing out in the new definition of hemorrhoid " objects of all treatments are not eliminate hemorrhoid bodies; but eliminate symptom; and the symptom removing hemorrhoid is more meaningful than change hemorrhoid body size, should be considered the standard of therapeutic effect ".These new treatment concept make the Therapeutic Principle of hemorrhoid clear, and the non-operative treatment importance that especially basic pharmaceutical is treated is appeared suddenly.Now mostly the suggestion of scholar be more than ninety percent hemorrhoid patients can adopt non-operative treatment, only need surgical intervention less than the hemorrhoid patients of 10%.Reason is Drug therapy energy reducing swelling and alleviating pain, relief of symptoms, turn avoid the pain of operation and the complication of injection treatment, so most people is applicable to Drug therapy.Medicine at present for hemorrhoid mainly contains antibiotics, hemorrhage and Chinese patent medicine, front two class medicines often take stopgap measures refractory this, recurrence probability is large, of long duration often can worsen.In addition, at present drug treatment takes for oral administration or topical patch to need systemic Absorption to treat relieving constipation medicine in addition clinically, this kind of drug main will rely on softening stool, the impact of stool to anus blood stasis is reduced during defecation, thus alleviate the misery of hemorrhoid patients, but the basic state of an illness that this kind of medicine does not change hemorrhoid patients does not change the cause of disease in other words conj.or perhaps, and in fact the state of an illness is under development.
Summary of the invention
In view of the deficiencies in the prior art, the object of the present invention is to provide and a kind of there is antiinflammatory, analgesia, hemostasis, improve the external used medicine of the treatment hemorrhoid of vascular permeability effect.
In order to realize object of the present invention, inventor is studied by lot of experiments, finally obtains following technical scheme:
A kind of external preparation for the treatment of hemorrhoid, comprise active component and pharmaceutically acceptable adjuvant, described active component is prepared from through water extract-alcohol precipitation by the traditional Chinese medicinal material raw materials of following weight portion: Radix Sanguisorbae 8-13 part, Flos Lonicerae 8-13 part, Radix Stemonae 8-13 part, Rhizoma Chuanxiong 10-18 part, Flos Sophorae 10-18 part, Herba Agrimoniae 10-18 part, Herba portulacae 10-18 part, Fructus Arctii 25-35 part, Cortex Dictamni 25-35 part.
The external preparation for the treatment of hemorrhoid of the present invention, active component wherein is preferably prepared from through water extract-alcohol precipitation by the traditional Chinese medicinal material raw materials of following weight portion: Radix Sanguisorbae 10 parts, Flos Lonicerae 10 parts, the Radix Stemonae 10 parts, Rhizoma Chuanxiong 14 parts, 14 parts, Flos Sophorae, Herba Agrimoniae 14 parts, Herba portulacae 14 parts, Fructus Arctii 30 parts, Cortex Dictamni 30 parts.
The external preparation of above-mentioned treatment hemorrhoid can be prepared into gel, ointment, suppository or ointment.
Further preferably, when the external preparation of above-mentioned treatment hemorrhoid is prepared into gel, wherein said pharmaceutically acceptable adjuvant is selected from the two or more of carbomer, propylene glycol, glycerol, triethanolamine and cellulose derivative.
Further preferably, when the external preparation of above-mentioned treatment hemorrhoid is prepared into ointment, it is two or more that wherein said pharmaceutically acceptable adjuvant is selected from glyceryl monostearate, glycerol, propylene glycol, stearic acid, white vaseline, triethanolamine, sodium lauryl sulphate and ethyl hydroxybenzoate.
Further preferably, when the external preparation of above-mentioned treatment hemorrhoid is prepared into suppository, it is two or more that wherein said pharmaceutically acceptable adjuvant is selected from semi-synthetic fatty glyceride, glycerol, gelatin and Polyethylene Glycol.
Further preferably, when the external preparation of above-mentioned treatment hemorrhoid is prepared into ointment, it is two or more that wherein said pharmaceutically acceptable adjuvant is selected from glyceryl monostearate, paraffin, white vaseline, liquid paraffin, propylene glycol, P-hydroxybenzoic acid second and sorbester p17.
It should be noted that, according to Chinese medicine Historical Data Data About, the Chinese crude drug selected by the present invention has following function and cures mainly and originate:
Radix Sanguisorbae: cooling blood for hemostasis, heat-clearing and toxic substances removing, detumescence sore.Spit blood, spitting of blood, epistaxis, hematuria, has blood in stool, hemorrhoidal bleeding, dysentery, metrorrhagia, leucorrhea with red and white discharge, sore, carbuncle and painful swelling, eczema, pudendal pruritus, burn due to hot liquid or fire, snake bite and insect sting.Select the dry root of rosaceous plant Radix Sanguisorbae Sanguisorba officinalis L..
Flos Lonicerae: heat-clearing and toxic substances removing.Epidemic febrile disease is generated heat; Toxic-heat and blood stasis; Carbuncle furuncle; Sore throat and multi-infection disease.Be selected from the dry flower of caprifoliaceae plant Radix Ophiopogonis (Lonicera japonica Thunb).
The Radix Stemonae: nourishing the lung to keep the adverse QI downward cough-relieving, parasite killing.Cough for new chronic cough, pulmonary tuberculosis cough, pertussis; Outer for head louse, body louse, enterobiasis, pudendum Pruritus.Honey Radix Stemonae nourishing the lung to arrest cough.Be selected from the dried root of Stemonaceae plant Radix Stemonae Stemona sessilifolia (Miq.) Miq..
Rhizoma Chuanxiong: blood-activating and qi-promoting, wind-expelling pain-stopping.For pacifying nerve, positive wind syndrome of head headache, lump in the abdomen is suffered from abdominal pain, the twinge of the breast side of body, tumbling and swelling, headache, rheumatic arthralgia.Select the rhizome of samphire Rhizoma Chuanxiong.
Flos Sophorae: cooling blood for hemostasis; Liver heat removing and eyesight improving.Main discharging fresh blood stool; Hemorrhoid hematochezia; Dysentery; Hematuria; Stranguria with blood; Metrorrhagia; Spit blood; Epistaxis; Liver-heat is had a headache; Conjunctival congestion and swelling pain; Carbuncle skin infection.For having blood in stool, hemorrhoidal bleeding, dysentery, metrorrhagia, spit blood, epistaxis, liver-heat conjunctival congestion, has a headache dizzy.
Herba Agrimoniae: astringing to arrest bleeding, dysentery relieving, parasite killing.Be widely used in various hemorrhage card, such as: haematemesis, hematuria, have blood in stool, metrorrhagia, spitting of blood, epistaxis, dysentery, impairment caused by overstrain takes off power, carbuncle, traumatic injury, the cards such as wound hemorrhage.
Herba portulacae: heat-clearing and toxic substances removing, diuretic dries, loose blood detumescence, dust-collection sterilization, anti-inflammatory analgetic, hemostasis removing heat from blood.Cure mainly dysentery, enteritis, nephritis, puerperal, metrorrhagia, had blood in stool, the diseases such as mastitis.Select the young young stem and leaf of portulacaceous plant Herba Portulacae.
Fructus Arctii: the effect with dispelling wind and heat pathogens, lung qi dispersing rash, sore-throat relieving eliminating stagnation, removing toxic substances and promoting subsidence of swelling, cure mainly cough due to pathogenic wind-heat, laryngopharynx swelling and pain, macule not thoroughly, rubella pruritus, sore swollen toxin.Be selected from the dry mature fruit of feverfew Fructus Arctii Arctium lappa L..
Cortex Dictamni: heat clearing and damp drying; Dispelling wind for relieving itching; Removing toxic substances.Cure mainly the rubella caused by wind heat noxious dampness; Eczema; Scabies; Jaundice; Damp-heat arthralgia.Select the root bark of rutaceae shaggy-fruited dittany and Dictamnus angustifolius.
By the preparation technology of above-mentioned each traditional Chinese medicinal material raw materials preparation cost invention external preparation be: take Radix Sanguisorbae 8-13 part, Flos Lonicerae 8-13 part, Radix Stemonae 8-13 part, Rhizoma Chuanxiong 10-18 part, Flos Sophorae 10-18 part, Herba Agrimoniae 10-18 part, Herba portulacae 10-18 part, Fructus Arctii 25-35 part and the mixing of Cortex Dictamni 25-35 part, add the water of 10-12 times amount, soak 12h-16h, then decoct three times, first time decocts 1.5-2h, leaches medicinal liquid stand-by, second time adds the water of 8-10 times amount, decocts 1-1.5h, leaches medicinal liquid stand-by, add the water of 6-8 times amount for the third time, decoct 0.8-1h, leach medicinal liquid stand-by, merge three decocting liquids, filter, collect filtrate, 0.07MPa, when being evaporated to 65 DEG C at 60-70 DEG C, relative density is the extractum of 1.15, adding 95% (v/v) ethanol makes alcohol content reach 75% (v/v), stir, leave standstill 24 hours, filter, filtrate is at 0.07MPa, under 65 DEG C of conditions, concentrating under reduced pressure one-tenth is about 1.25 to relative density when 65 DEG C (relative water), and reclaim ethanol, obtain concentrated solution, by concentrated solution spraying dry, (condition is inlet temperature is 100 DEG C, leaving air temp is 80 DEG C, temperature of charge is 80 DEG C, atomizing pressure is 0.2 MPa, spray velocity is 5ml/s.), pulverize 80 mesh sieves, obtain clear paste powder; By clear paste powder and pharmaceutically acceptable adjuvant conveniently technique be prepared into gel, ointment, suppository or ointment.
Chinese medicine for external application provided by the present invention reaches effect of radical cure hemorrhoid by the comprehensive functions such as microcirculation, antiinflammatory, analgesia of stopping blooding, improve, and is applicable to the intractable hemorrhoid for the treatment of, is especially applicable to treating hemorrhagic hemorrhoid.Found by animal experiment study, Chinese medicine for external application of the present invention can suppress the auris dextra swelling of caused by dimethylbenzene xylene inflammation mouse model, reduce the rectum vein permeability of Oleum Tiglii hemorrhoid rat model, analgesic effect is also comparatively remarkable, and the first-line drug that can be used as hemorrhoid treating is developed simultaneously.In addition, formula of the present invention not only can play respective effect of component, can embody again the cooperative effect of said components, mutual penetration enhancement, enhance the therapeutic effect of hemorrhoid.
Specific embodiment
We find in screening experiment, and in pharmaceutical composition of the present invention, the consumption of often kind of traditional Chinese medicinal material raw materials slightly changes among a small circle, and it all has the biological activity for the treatment of hemorrhoid.Now further illustrate pharmaceutical composition of the present invention and preparation method thereof and therapeutic effect by following embodiment, but protection scope of the present invention is not limited to embodiment.
The preparation of embodiment 1 Chinese medicine clear paste powder
Take Radix Sanguisorbae 10 parts, Flos Lonicerae 10 parts, the Radix Stemonae 10 parts, Rhizoma Chuanxiong 14 parts, 14 parts, Flos Sophorae, Herba Agrimoniae 14 parts, Herba portulacae 14 parts, Fructus Arctii 30 parts and Cortex Dictamni 30 parts mixing, add the water of 12 times amount, soak 12h-16h, then decoct three times, first time decocts 1.5-2h, leaches medicinal liquid stand-by, second time adds the water of 10 times amount, decocts 1-1.5h, leaches medicinal liquid stand-by, add the water of 8 times amount for the third time, decoct 0.8-1h, leach medicinal liquid stand-by, merge three decocting liquids, filter, collect filtrate, 0.07MPa, when being evaporated to 65 DEG C at 60-70 DEG C, relative density is the extractum of 1.15, adding 95% (v/v) ethanol makes alcohol content reach 75% (v/v), stir, leave standstill 24 hours, filter, filtrate is at 0.07MPa, under 65 DEG C of conditions, concentrating under reduced pressure one-tenth is about 1.25 to relative density when 65 DEG C (relative water), and reclaim ethanol, obtain concentrated solution, by concentrated solution spraying dry, (condition is inlet temperature is 100 DEG C, leaving air temp is 80 DEG C, temperature of charge is 80 DEG C, atomizing pressure is 0.2 MPa, spray velocity is 5ml/s.), pulverize 80 mesh sieves, obtain clear paste powder.
The preparation of embodiment 2 Chinese medicine gel
Chinese medicine clear paste powder 20g
Carbomer 15g
Propylene glycol 75ml
Glycerol 75ml
Triethanolamine is appropriate
Purified water adds to 1000ml
Preparation technology: carbomer is slowly joined in the water of recipe quantity about 50%, limit edged stirs until form transparent gel-type vehicle, Chinese medicine clear paste powder embodiment 1 prepared is dissolved in suitable quantity of water, add again in substrate, stir, add propylene glycol, glycerol, purified water to full dose, triethanolamine adjust ph, to neutral, to obtain final product.
The preparation of embodiment 3 Chinese medicine ointment
Chinese medicine clear paste powder 20g
Glyceryl monostearate 100g
Paraffin 100g
White vaseline 50g
Liquid paraffin 55g
Propylene glycol 50g
Sorbester p17 6g
Ethylparaben 1.2g
Purified water adds to 1000ml
Preparation technology: get paraffin, glyceryl monostearate, white vaseline, liquid paraffin, propylene glycol, sorbester p17 and ethylparaben heat fused keep 80 DEG C in water-bath, the water of 80 DEG C is slowly added under stirring, limit edged is stirred to condensation, i.e. ointment base.Get Chinese medicine clear paste powder to be dissolved in appropriate purified water, join in substrate, finally add water to full dose, to obtain final product.
The preparation of embodiment 4 Chinese medicine suppository
Chinese medicine clear paste powder 20g
Semi-synthetic fatty glyceride 350g
Tween 80 1.5g
Preparation technology: get semi-synthetic fatty glyceride and put in vessel, heating in water bath melts, and treats that temperature is down to about 50 DEG C, add Tween 80, stir, add Chinese medicine clear paste powder, stir, rear injection scribbles the bolt mould of lubricant to slightly overflowing die orifice for degree, cooling, spilling of pruning after solidifying part, the demoulding, quality inspection, packaging, to obtain final product.
The preparation of the blank ointment of comparative example
Glyceryl monostearate 100g
Paraffin 100g
White vaseline 50g
Liquid paraffin 55g
Propylene glycol 50g
Sorbester p17 6g
Ethylparaben 1.2g
Purified water adds to 1000ml
Preparation technology: get paraffin, glyceryl monostearate, white vaseline, liquid paraffin, propylene glycol, sorbester p17 and ethylparaben heat fused keep 80 DEG C in water-bath, the purified water of 80 DEG C is slowly added under stirring, limit edged is stirred to condensation, i.e. blank ointment.
Embodiment 5 Chinese medicine ointment is on the impact of rat Oleum Tiglii hemorrhoid model
Modeling method: Oleum Tiglii is a kind of conventional proinflammatory agent, conventional Oleum Tiglii mixed liquor 1 part of distilled water, 4 parts of pyridines, 5 parts of ether and 10 part of 15% Oleum Tiglii diethyl ether solution preparation.Be stained with Oleum Tiglii with 10mg cotton balls, the cotton balls after soaking put into rat anal, stops and take out after 15 seconds.
36 SD rats (about 200 grams) are divided into three groups at random by body weight: model control group (the blank ointment of administration), Ma Yinglong group (administration MAYINGLONG MUSK HEMORRHOID UNGUENTUM), test group (Chinese medicine ointment prepared by administration embodiment 3), often organize 12.Rat carries a few days ago drop rectum with drug, and every day sooner or later respectively once, is stained with medicine with 10mg cotton balls, cotton balls is filled in internal rectum, during next administration, first should check whether internal rectum has cotton balls (should take out if any cotton balls).Last administration should after modeling 2 hours.Last administration is after 5 hours, every blue normal saline solution (2ml/kg) of she Wen of rat intravenous injection 1%, sacrificed by exsanguination animal after 40 minutes, cut-off intestinal and perianal tissue, use acetone normal saline 7:3 solution soaking 48 hours after weighing, centrifugal 10 minutes of 3000rpm, gets supernatant and surveys absorbance in 590nm, as evaluation vascular permeability index, the results are shown in Table 1.
Can be found out by the result of the test of table 1, Chinese medicine ointment of the present invention well can reduce the rectum vein permeability of Oleum Tiglii hemorrhoid model mice, with Ma Yinglong group there was no significant difference.
The comparison of each treatment group of table 1 and model control group absorbance
| Group | Rat number of elements | Absorbance |
| Model control group | 12 | 0.150±0.041 |
| Ma Yinglong group | 12 | 0.107±0.046 ★ |
| Test group | 12 | 0.113±0.030 ★ |
★compare with matched group, P < 0.05;
★ ★compare with matched group, P < 0.01.
Embodiment 6 Chinese medicine ointment is on the impact of mice dimethylbenzene inflammatory model
36 KM mices, male and female half and half, body weight 25-30 gram, is divided into three groups at random by body weight: model control group (the blank ointment of administration), Ma Yinglong group (administration MAYINGLONG MUSK HEMORRHOID UNGUENTUM), test group (Chinese medicine ointment prepared by administration embodiment 3), often organizes 12.Get dimethylbenzene 20 μ l, be applied to mouse right ear.Get after 30min and be respectively evenly applied to mouse right ear respectively by reagent, put to death after administration 3h.Along auricle baseline, place cuts two ears, lays auricle, weigh with 8mm card punch at the same position of left and right ear, and the ear method of double differences=auris dextra sheet weight-left auricle weight, the results are shown in Table 2.
Can be found out by the result of the test of table 2, Chinese medicine ointment of the present invention has obvious antiinflammatory action, and antiinflammatory curative effect is better than Ma Yinglong treatment group.
The each treatment group of table 2 and the model control group ear method of double differences compare
| Group | Rat number of elements | The ear method of double differences (mg) |
| Model control group | 12 | 7.17±2.47 |
| Ma Yinglong group | 12 | 4.97±2.61 ★ |
| Test group | 12 | 3.08±1.83 ★★● |
★compare with matched group, P < 0.05;
★ ★compare with matched group, P < 0.01;
●with Ma Yinglong group comparatively, P < 0.05;
● ●compare with Ma Yinglong group, P < 0.01.
Embodiment 7 Chinese medicine ointment is on the impact of pain model in mice
KM mice 36, male and female half and half, body weight 25-30 gram, is divided into three groups at random by body weight: model control group (the blank ointment of administration), Ma Yinglong group (administration MAYINGLONG MUSK HEMORRHOID UNGUENTUM), test group (Chinese medicine ointment prepared by administration embodiment 3), often organizes 12.Mice anum administration, is stained with medicine with 10mg cotton balls, cotton balls is filled in internal rectum, once a day, continuous three days, after last administration 30 minutes, injects 5% formalin 0.2ml apart from anus 3.5cm place rectal wall.Writhing number of times in record mice 20 minutes.Concrete outcome is in table 3.
Can be found out by the result of the test of table 2, Chinese medicine ointment of the present invention has fairly obvious analgesic effect, with Ma Yinglong group there was no significant difference.
The each treatment group of table 3 and model control group writhing number of times compare
| Group | Rat number of elements | Writhing number of times |
| Model control group | 12 | 48.3±11.7 |
| Ma Yinglong group | 12 | 36.7±12.6 ★ |
| Test group | 12 | 33.0±15.1 ★ |
★compare with matched group, P < 0.05;
★ ★compare with matched group, P < 0.01.
Claims (7)
1. treat the external preparation of hemorrhoid for one kind, comprise active component and pharmaceutically acceptable adjuvant, it is characterized in that described active component is prepared from through water extract-alcohol precipitation by the traditional Chinese medicinal material raw materials of following weight portion: Radix Sanguisorbae 8-13 part, Flos Lonicerae 8-13 part, Radix Stemonae 8-13 part, Rhizoma Chuanxiong 10-18 part, Flos Sophorae 10-18 part, Herba Agrimoniae 10-18 part, Herba portulacae 10-18 part, Fructus Arctii 25-35 part, Cortex Dictamni 25-35 part.
2. treat the external preparation of hemorrhoid according to claim 1, it is characterized in that described active component is prepared from through water extract-alcohol precipitation by the traditional Chinese medicinal material raw materials of following weight portion: Radix Sanguisorbae 10 parts, Flos Lonicerae 10 parts, the Radix Stemonae 10 parts, Rhizoma Chuanxiong 14 parts, 14 parts, Flos Sophorae, Herba Agrimoniae 14 parts, Herba portulacae 14 parts, Fructus Arctii 30 parts, Cortex Dictamni 30 parts.
3. according to claim 1 or 2, treat the external preparation of hemorrhoid, it is characterized in that: described external preparation is gel, ointment, suppository or ointment.
4. treat the external preparation of hemorrhoid according to claim 3, it is characterized in that: when described external preparation is gel, described pharmaceutically acceptable adjuvant is selected from the two or more of carbomer, propylene glycol, glycerol, triethanolamine and cellulose derivative.
5. treat the external preparation of hemorrhoid according to claim 3, it is characterized in that: when described external preparation is ointment, it is two or more that described pharmaceutically acceptable adjuvant is selected from glyceryl monostearate, glycerol, propylene glycol, stearic acid, white vaseline, triethanolamine, sodium lauryl sulphate and ethyl hydroxybenzoate.
6. treat the external preparation of hemorrhoid according to claim 3, it is characterized in that: when described external preparation is suppository, it is two or more that described pharmaceutically acceptable adjuvant is selected from semi-synthetic fatty acid glyceride, glycerol, gelatin and Polyethylene Glycol.
7. treat the external preparation of hemorrhoid according to claim 3, it is characterized in that: when described external preparation is ointment, it is two or more that described pharmaceutically acceptable adjuvant is selected from glyceryl monostearate, paraffin, white vaseline, propylene glycol, P-hydroxybenzoic acid second and sorbester p17.
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| CN105169456B (en) * | 2015-08-25 | 2018-06-01 | 东莞市达庆医疗器械有限公司 | A kind of medical bio hemorrhoid hydrogel functional dressing and preparation method thereof |
| CN105943655A (en) * | 2016-05-04 | 2016-09-21 | 昆明理工大学 | Compound ointment for treating hemorrhoids and preparation method of compound ointment |
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| CN102000175A (en) * | 2010-11-17 | 2011-04-06 | 黄文珍 | Traditional Chinese medicine composition for treating hemorrhoids and preparation method thereof |
| CN102772598A (en) * | 2012-08-20 | 2012-11-14 | 解连新 | Traditional Chinese medicine for treating bacillary dysentery |
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| CN102000175A (en) * | 2010-11-17 | 2011-04-06 | 黄文珍 | Traditional Chinese medicine composition for treating hemorrhoids and preparation method thereof |
| CN102772598A (en) * | 2012-08-20 | 2012-11-14 | 解连新 | Traditional Chinese medicine for treating bacillary dysentery |
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| Title |
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| 肛肠安胶囊治疗痔疮188例疗效观察;赵国鸣等;《云南中医中药杂志》;20091231;第30卷(第10期);37-38 * |
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