CN105999063A - Medicinal preparation for treating qi stagnation and blood stasis syndrome after operation for thyroid cancer - Google Patents
Medicinal preparation for treating qi stagnation and blood stasis syndrome after operation for thyroid cancer Download PDFInfo
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Abstract
The invention specifically relates to a medicinal preparation for treating a qi stagnation and blood stasis syndrome after an operation for the thyroid cancer and a preparation method thereof, belonging to the field of traditional Chinese medicine and pharmacy. The medicinal preparation is prepared from Japanese angelica tree root bark, beechey fig leaf, Corydalis decumbens, Agrimonia pilosa, curcuma rhizome, Alocasia odora, pseudobulb of appendiculate Cremastra, Litsea verticillata, Radix Calystegia japonica and honey-fried licorice root in a certain weight ratio. The medicinal preparation is capable of supplementing qi, removing blood stasis, invigorating blood circulation, dredging channels, reducing phlegm, resolving masses and clearing away heat and toxic matters; the medicinal preparation is targeted for a patient with the qi stagnation and blood stasis syndrome after the operation for the thyroid cancer and capable of supporting right, dispelling evil and simultaneously treating principal and subordinate symptoms, can substantially improve clinical symptoms of the patient and enhances Karnofsky Performance Status; the medicinal preparation is likely to inhibit secretion of thyrotropic hormone by pituitary gland and reduce TG; moreover, the medicinal preparation can alleviate adverse reaction of treatment with western medicines, mitigate discomfort of the patient and improve life quality, and is a safe effective adjuvant treatment method.
Description
Technical field
The invention belongs to tcm field, be specifically related to a kind of pharmaceutical preparation treating the postoperative syndrome of qi stagnation and blood stasis of thyroid carcinoma
And preparation method thereof.
Background technology
Thyroid carcinoma is a clinical common class neck malignant tumor, sickness rate in China just in the gesture of rising year by year.Mesh
The prevalence of front Chinese population thyroid nodule is 18.6%, and wherein Malignant Nodules (i.e. thyroid carcinoma) accounts for 5%～10%, pathology
Type is broadly divided into papillary carcinoma, filter blocking cancer, undifferentiated carcinoma, medullary carcinoma etc..In addition to except diagnostic techniques, prosperity is improved increasingly, no
When diet, excessive stress, lonizing radiation irradiation may be all predisposition thereto.
Shape adenocarcinoma be in current endocrine system disease sickness rate the highest malignant tumor, account for whole body malignant tumor
1%, in patient groups, women number is 23 times of male.Recent Epidemiological study prompting, multiple countries in the world
The sickness rate of this disease shows and rises situation faster.Thyroid carcinoma is generally divided into papillary carcinoma, follicular cells cancer, undifferentiated
Cancer, parafollicular cell cancer and thyroid lymphoma.Papillary carcinoma and filter blocking cancer belong to differentiated thyroid carcinoma together
(DTC), in thyroid carcinoma, its disease rates is the highest, reaches 90%.
Present stage, the integration scenario of western medical treatment differentiated thyroid carcinoma: operation radioiodine ablation hormone suppression is controlled
Treat.Doctor trained in Western medicine, while implementing Radical Thyroidectomy, also brings certain side reaction, such as, treats this after being ill, and bone marrow is made
Blood function is suppressed, and causes leukocyte, hemoglobin, thrombocytopenia, it is difficult to recover normal at short notice；Postoperative fatigue is weary
Power, neck and shoulder part swelling is numb, twinge；Emotion changes after thyroxin suppression therapy, nervous many situations such as uncomfortable in chest, serious shadow
Ring the quality of life of patient.Even if furthermore the patient of thyroid carcinoma has carried out operative treatment, the most still there is part " pathogen " residual
Body, becomes the root of relapse and metastasis.
Thyroid carcinoma is without corresponding names of disease of tcm, according to the Clinical symptoms of primary disease, can be classified as " tumor ", " stony goiter " model
Farmland.The pathogenesis of thyroid carcinoma can be summarized as " gas ", " expectorant ", " stasis of blood ", " malicious ".Depression and stagnation of QI and poly-expectorant；Mental disorder stagnate form tired；Expectorant
Tired friendship is hindered and is made poison；Ecchymosis stagnated fire and impairment of YIN, cloudy damage of essence consumption and feel frustrated and cause " deficiency of vital energy "." blood stasis " is the commonly encountered diseases of thyroid carcinoma
Reason factor, is also to affect primary disease generation, conversion, the fundamental of prognosis, and ecchymosis is tied pathogenic mutually, can damage internal organs, and QI and blood decays
And cause deficient.The traditional Chinese medical science thinks " healthy energy deposit in, heresy can not be done ", " being gathered of heresy, its gas must void ".At present, increasing evidence
Show that middle thyroid cancer patients is the most actively aided with Chinese medicine and can make up operative treatment deficiency, alleviate endocrine therapy
Untoward reaction, reduce postoperative Serum Thyroglobulin thus prevent cancerous protuberance recurrence and transfer, improve patient clinical disease
Shape, improves patients ' life quality.Therefore, Chinese medicine in becoming thyroid carcinoma comprehensive therapeutic plan requisite
Point.
Summary of the invention
It is an object of the present invention to provide a kind of pharmaceutical preparation treating the postoperative syndrome of qi stagnation and blood stasis of thyroid carcinoma, it can have
Effect improves the clinical symptoms of the qi depression to blood stasis such as the postoperative spiritlessness and weakness of thyroid carcinoma, susceptible, the deficiency of QI with disinclination to talk of spontaneous perspiration, alleviates endocrine and controls
The untoward reaction treated, reduces postoperative Serum Thyroglobulin thus prevents cancerous protuberance recurrence and transfer, improve patient clinical
Symptom, improves patients ' life quality.
For achieving the above object, the present invention adopts the following technical scheme that:
A kind of pharmaceutical preparation treating the postoperative syndrome of qi stagnation and blood stasis of thyroid carcinoma, it is by Cortex Araliae Elatae Radicis, Caulis et Folium Fici beecheyanae, Rhizoma Corydalis Decumbentis, celestial being
Crane grass, Rhizoma Curcumae, Rhizoma alcasiae odorae, Pseudobulbus Cremastrae Seu Pleiones, Radix litseae verticillatae, Radix Calystegiae sepii, Radix Glycyrrhizae Preparata are that medicinal raw material is made.
The present invention defers to differential diagnosis of diseases and the dialectical principle combined thirty years of age, and prescription selects medicine many with inrigorating qi and promoting blood circulation, dredging collateral dissipating blood stasis, clearly
Thermal detoxification, the product of dissipating phlegm and resolving masses, heighten the effect of a treatment for making all medicines functionally complement each other；The property of medicine is made mutually and helps mutually to lower
Toxicity, inventor defers to the compatibility relationship of monarch, further preferably goes out following scheme:
A kind of pharmaceutical preparation treating the postoperative syndrome of qi stagnation and blood stasis of thyroid carcinoma, it is by the medicinal raw material of following weight
Medicine is made: Cortex Araliae Elatae Radicis 10-15 part, Caulis et Folium Fici beecheyanae 20-25 part, Rhizoma Corydalis Decumbentis 8-13 part, Herba Agrimoniae 6-9 part, Rhizoma Curcumae 7-12 part, Rhizoma alcasiae odorae 6-
11 parts, Pseudobulbus Cremastrae Seu Pleiones 7-12 part, Radix litseae verticillatae 12-17 part, Radix Calystegiae sepii 8-13 part, Radix Glycyrrhizae Preparata 5-8 part.
Further, a kind of pharmaceutical preparation treating the postoperative syndrome of qi stagnation and blood stasis of thyroid carcinoma, it is by following weight
Medicinal crude drug make: Cortex Araliae Elatae Radicis 12 parts, Caulis et Folium Fici beecheyanae 25 parts, Rhizoma Corydalis Decumbentis 12 parts, Herba Agrimoniae 8 parts, Rhizoma Curcumae 10 parts, Rhizoma alcasiae odorae 9 parts,
Pseudobulbus Cremastrae Seu Pleiones 12 parts, Radix litseae verticillatae 15 parts, Radix Calystegiae sepii 10 parts, Radix Glycyrrhizae Preparata 6 parts.
Fang Zhong: Cortex Araliae Elatae Radicis invigorating QI and tranquilization, the nourishing kidney of strong essence, expelling wind and activating blood circulation；Caulis et Folium Fici beecheyanae invigorating the spleen and replenishing QI, invigorating the spleen for eliminating dampness, strong muscle is strengthened
Bone, promoting blood circulation to remove obstruction in the collateral, subduing swelling and detoxicating, two medicine 5 invigorating the spleen and replenishing QI, promoting blood circulation to remove obstruction in the collateral, have nourishing the liver and kidney concurrently, the effect of bone and muscle strengthening, for monarch
Medicine.Rhizoma Corydalis Decumbentis promoting blood circulation to remove obstruction in the collateral, promoting the circulation of QI to relieve pain；Rhizoma alcasiae odorae heat-clearing and toxic substances removing, promoting the circulation of QI to relieve pain, mass dissipating and swelling eliminating；Pseudobulbus Cremastrae Seu Pleiones heat-clearing and toxic substances removing, reduces phlegm
Eliminating stagnation, three medicine 5 promoting flow of QI and blood dissipating blood stasis, dissipating phlegm and resolving masses, heat-clearing and toxic substances removing is ministerial drug.Rhizoma Curcumae: circulation of qi promoting removing blood stasis, removing food stagnancy pain relieving, red crowned crane
Grass qi-restoratives convergence, removing toxic substances；Radix litseae verticillatae dispelling wind and removing obstruction in the collateral, promoting blood circulation and detumescence, pain relieving；Radix Calystegiae sepii QI invigorating qi-restoratives, reunion of fractured tendons and bones, removing toxic substances；Process
Radix Glycyrrhizae spleen reinforcing stomach function regulating, Yiqi and vein recovery, for adjuvant.
All medicines 5 are with there being benefiting qi and removing blood stasis, and promoting blood circulation to remove obstruction in the collateral, dissipating phlegm and resolving masses, the effect of heat-clearing and toxic substances removing, for the postoperative gas of thyroid carcinoma
Stagnant Patients with Blood Stasis Syndrome, strengthening vital QI to eliminate pathogenic factors, treating both the principal and secondary aspects of a disease, the tcm clinical practice symptom of patient can be significantly improved, improve Ka Shi scoring；To pressing down
The secretion of human thyrotropin processed, reduction TG have certain trend；Also can alleviate the untoward reaction of western medical treatment, improve and suffer from
Person's malaise symptoms, improves the quality of living, and is one safely and effectively auxiliary treating method.
Used by the present invention, the property of medicine of all medical materials is as follows.
Cortex Araliae Elatae Radicis: [source] is root bark or the bark of Araliaceae east area of the Liao River, coextensive with eastern and southern Liaoning Province wood.Spring gathers, and dries.[nature and flavor] are pungent,
Flat, slightly poisonous.[function cures mainly] invigorating QI and tranquilization, the nourishing kidney of strong essence, expelling wind and activating blood circulation.Control neurasthenia, rheumatic arthritis, diabetes
And the card such as weak, the insufficiency of kidney-YANG of yang deficiency gas.
Caulis et Folium Fici beecheyanae: [nature and flavor] are sweet；Light；Warm in nature.[return through] lung；Spleen；Kidney channel.[function cures mainly] invigorating middle warmer spleen invigorating；Wind-damp dispelling；Live
Blood dredging collateral.The main deficiency of vital energy is weak；Extremity are aching and limp；Rheumatic arthralgia；Stiffness of the muscle and joint；Traumatic injury；Amenorrhea；Galactostasis.
Rhizoma Curcumae: [nature and flavor] are pungent, bitter, temperature.[return through] returns liver, spleen channel.[function cures mainly] circulation of qi promoting removing blood stasis, removing food stagnancy pain relieving.For
Abdominal mass mass in the abdomen, blood stasis amenorrhea, food stagnation distending pain；Early cervical carcinoma.
Rhizoma alcasiae odorae: [nature and flavor] are micro-pungent, puckery, cold in nature, poisonous；[return through] GUIXIN, liver, gallbladder, large intestine channel.[function cures mainly] heat clearing away solution
Poison, promoting the circulation of QI to relieve pain, mass dissipating and swelling eliminating.Cure mainly influenza, flu, stomachache, pulmonary tuberculosis, rheumatic ostalgia, furuncle, swollen ulcer drug, scrofula, attached
Bone carbuncle, class is bald, scabies, worm venom.
Pseudobulbus Cremastrae Seu Pleiones: [nature and flavor] are sweet, micro-pungent, cool.[return through] returns liver, spleen channel.[function cures mainly] heat-clearing and toxic substances removing, dissipating phlegm and resolving masses.
For carbuncle furunculosis, scrofula sucutaneous nodule, tuberculous lymphadenitis, snake bite and insect sting.
Radix litseae verticillatae: [nature and flavor] are bitter；Pungent；Temperature.[return through] lung；Liver Channel.[function cures mainly] dispelling wind and removing obstruction in the collateral；Promoting blood circulation and detumescence；Pain relieving.
Main air wet arthritis；Lumbago and skelalgia；Quadriplegia；Dysmenorrhea；Treating swelling and pain by traumatic injury.[usage and dosage] takes orally: pan-fried soup, stem, leaf 5-10g,
Root 15-30g；Or infusing drugs in wine.External: fresh leaf is appropriate, mashes deposited.
Radix Calystegiae sepii: [nature and flavor] are sweet；Micro-hardship；Temperature.[return through] lung；Liver；Kidney channel.[function cures mainly] QI invigorating qi-restoratives；Reunion of fractured tendons and bones；
Removing toxic substances；Parasite killing.Main erysipelas；Strain；Incised wound；Ascariasis [usage and dosage] is taken orally: decoct soup, 10-15g；Or strand juice.External is smash deposited.
Rhizoma Corydalis Decumbentis: [nature and flavor] are bitter, micro-pungent, temperature.[return through] returns Liver Channel.[function cures mainly] promoting blood circulation to remove obstruction in the collateral, promoting the circulation of QI to relieve pain.For
Apoplectic hemiplegia, injury from falling down, rheumatic arthritis, sciatica.
Herba Agrimoniae: [nature and flavor] are bitter, puckery is flat.[return through] GUIXIN, Liver Channel.[function cures mainly] astringing to arrest bleeding, preventing the attack (or recurrence) of malaria, dysentery relieving, solve
Poison.For hemoptysis, spit blood, metrostaxis, malaria, dysentery, de-power impairment caused by overstrain, carbuncle sore tumefacting virus, pudendal pruritus leukorrhagia.
Radix Glycyrrhizae Preparata: [nature and flavor] are sweet is flat.[return through] GUIXIN, lung, spleen, stomach warp.[function cures mainly] spleen reinforcing stomach function regulating, Yiqi and vein recovery.
For weakness of the spleen and stomach, fatigue and weakness, severe palpitation, irregularly intermittent and regularly intermittent pulse.[usage and dosage] 1.5～9g.
It is a further object to provide the system of a kind of pharmaceutical preparation treating the postoperative syndrome of qi stagnation and blood stasis of thyroid carcinoma
Preparation Method.
In order to preferably express the pharmaceutical preparation of the present invention, pharmaceutical preparation of the present invention can be by Cortex Araliae Elatae Radicis, Caulis et Folium Fici beecheyanae, summer
Nothing, Herba Agrimoniae, Rhizoma Curcumae, Rhizoma alcasiae odorae, Pseudobulbus Cremastrae Seu Pleiones, Radix litseae verticillatae, Radix Calystegiae sepii, Radix Glycyrrhizae Preparata or its water or its extractive with organic solvent are activity
Composition, is prepared from according to routine techniques.
Pharmaceutical preparation of the present invention can also optionally add applicable medicine and can connect when being prepared as peroral dosage form medicament
The carrier being subject to, described pharmaceutically acceptable carrier is selected from: mannitol, sorbitol, sodium pyrosulfite, sodium sulfite, sulfydryl second
Acid, methionine, injection Vitamin B_6 DTA calcium sodium, acetate, phosphate, aminoacid, sodium chloride, potassium chloride, sodium lactate, xylitol,
Maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, silicon derivative, cellulose and
Its derivant, alginate, gelatin, polyvinylpyrrolidone, glycerol, POLYSORBATE 80, agar, calcium carbonate, calcium bicarbonate, surface activity
Agent, Polyethylene Glycol, cyclodextrin, beta-schardinger dextrin-, phospholipid material, Kaolin, Pulvis Talci, calcium stearate, magnesium stearate etc..
The described peroral dosage form of the present invention can be capsule, tablet, granule, pill, powder, sublimed preparation, unguentum, etc.
Deng；More preferably tablet, capsule, granule, the most preferably capsule.
Present invention also offers the preparation method of a kind of Chinese medicinal capsule for thyroid carcinoma with bone pain in patients with metastatic, it include as
Lower step: taken Cortex Araliae Elatae Radicis, Caulis et Folium Fici beecheyanae, Rhizoma Corydalis Decumbentis, Herba Agrimoniae, Rhizoma Curcumae, Rhizoma alcasiae odorae, Pseudobulbus Cremastrae Seu Pleiones, Radix litseae verticillatae, Radix Calystegiae sepii by prescription, processed
Radix Glycyrrhizae powder is broken into coarse powder, the water soaking of 3-10 times of weight portion of addition 3-4 hour, decocts 1-2 hour, filtrate, filtering residue are collected by filtration
Add water 3-6 times for medical material weight portion and decoct 1-1.5 hour, collecting decoction, filter, filtrate reduced in volume to relative density is
1.06-1.12 (60 DEG C of surveys), adds ethanol and makes alcohol content reach 40-50% (preferably 45%), stand 12 hours, filter, and filtrate is returned
Receiving ethanol, being concentrated into 60 DEG C and recording relative density is 1.15-1.20, uses spray drying method to make granule, fills after granulate, sterilizing
Enter capsule shells and get final product.
Another object of the present invention is that protection said medicine preparation is being prepared for thyroid carcinoma with bone pain in patients with metastatic medicine
Purposes.The clinical observation result of the test prompting of embodiment 10 medicine of the present invention syndrome of qi stagnation and blood stasis postoperative to thyroid carcinoma patient:
Medication therapy groups therapeutic effect of the present invention is notable, and after treatment, two groups of patient clinical comprehensive therapeutic effects compare, and treatment group total effective rate is
95.6%, and matched group total effective rate is 77.2%, two groups of total effective rate comparing differences statistically significant (P ＜ 0.05), this
The total effective rate of invention medication therapy groups is higher；Two groups of main diseases (spiritlessness and weakness, deficiency of QI with disinclination to talk, spontaneous perspiration mesh susceptible, dizzy
String, neck and shoulder part swelling twinges) compare, the main disease integration of medication therapy groups of the present invention is significantly lower than matched group, and two groups are compared
Difference statistically significant (P ＜ 0.05)；Two groups of Evaluation on quality of lifes compare: treatment group total effective rate 95.6%；And matched group
Total effective rate 81.8%, the quality of life improvement situation for the treatment of group patient is substantially better than matched group, the statistically significant (P of difference
＜ 0.05)；After treatment, treatment group TG value is obviously reduced, comparing difference statistically significant (P ＜ 0.05) front with treatment, and compares
Organize and compare before treatment, no significant difference, compares between two groups after treatment, difference statistically significant (P ＜ 0.05), controls
What treatment group TG value reduced becomes apparent from；Treatment group during observing, FT3、FT4And TSH there is no significant change, Chinese medicine composition is described
Thing is the least for the function effect of thyroid gland hormone, treatment group patient without any subjective uncomfortable, blood, urine, stool routine examination and
The heart, Liver and kidney function etc. check exception all do not occur.
The most compared with prior art, the method have the advantages that
(1) mild in medicine property of the present invention and, animal experiment and clinical trial all show that safety of medicine coefficient of the present invention is high, bad instead
Should lack.
(2) present invention is based on theory of Chinese medical science, and prescription is rigorous, and monarch compatibility relationship is clear and definite, selects YAOJING to work as, has
Mutiple Targets, too many levels, multi-level comprehensive regulation effect, have a benefiting qi and removing blood stasis, promoting blood circulation to remove obstruction in the collateral, dissipating phlegm and resolving masses, the effect of heat-clearing and toxic substances removing,
For thyroid carcinoma postoperative syndrome of qi stagnation and blood stasis patient, strengthening vital QI to eliminate pathogenic factors, treating both the principal and secondary aspects of a disease, the tcm clinical practice disease of patient can be significantly improved
Shape, improves Ka Shi scoring, improves patients ' life quality.
(3) the reduction TG trend that medicine of the present invention is certain, can prevent and delay recurrence and the transfer of thyroid carcinoma, clinical total
Effective percentage is high.
(4) present invention can be prepared as multiple oral formulations, it is to avoid takes inconvenience, the shortcoming of patient compliance difference.
Detailed description of the invention
Further describing the present invention below by way of specific embodiment, the present invention is not limited only to following example.At this
In bright scope or without departing from present disclosure, spirit and scope, change that the present invention is carried out, combine or replace
Change, will be apparent to the person skilled in the art, and be included within the scope of the present invention.
Embodiment 1 capsule
Prescription: Cortex Araliae Elatae Radicis 12 parts, Caulis et Folium Fici beecheyanae 25 parts, Rhizoma Corydalis Decumbentis 12 parts, Herba Agrimoniae 8 parts, Rhizoma Curcumae 10 parts, Rhizoma alcasiae odorae 9 parts, mountain are kind
12 parts of mushroom, Radix litseae verticillatae 15 parts, Radix Calystegiae sepii 10 parts, Radix Glycyrrhizae Preparata 6 parts.
Preparation method: by prescription take Cortex Araliae Elatae Radicis, Caulis et Folium Fici beecheyanae, Rhizoma Corydalis Decumbentis, Herba Agrimoniae, Rhizoma Curcumae, Rhizoma alcasiae odorae, Pseudobulbus Cremastrae Seu Pleiones, Radix litseae verticillatae,
Radix Calystegiae sepii, Radix Glycyrrhizae Preparata are ground into coarse powder, the water soaking of 6 times of weight portions of addition 3-4 hour, decoct 1-2 hour, filter is collected by filtration
Liquid, filtering residue adds water as 5 times of medical material weight portion decoctions 1-1.5 hour, collecting decoction, filters, and filtrate reduced in volume is to the closeest
Degree is 1.08 (60 DEG C of surveys), adds ethanol and makes alcohol content reach 45%, stand 12 hours, filters, filtrate recycling ethanol, be concentrated into 60
DEG C recording relative density is 1.18, uses spray drying method to make granule, loads capsule shells and get final product after granulate, sterilizing.This enforcement
Capsule every loading amount 0.3g, is equivalent to crude drug 0.9g.
Embodiment 2 capsule
Prescription: Cortex Araliae Elatae Radicis 10 parts, Caulis et Folium Fici beecheyanae 22 parts, Rhizoma Corydalis Decumbentis 8 parts, Herba Agrimoniae 6 parts, Rhizoma Curcumae 10 parts, Rhizoma alcasiae odorae 8 parts, mountain are kind
10 parts of mushroom, Radix litseae verticillatae 15 parts, Radix Calystegiae sepii 12 parts, Radix Glycyrrhizae Preparata 7 parts.
Preparation method: by prescription take Cortex Araliae Elatae Radicis, Caulis et Folium Fici beecheyanae, Rhizoma Corydalis Decumbentis, Herba Agrimoniae, Rhizoma Curcumae, Rhizoma alcasiae odorae, Pseudobulbus Cremastrae Seu Pleiones, Radix litseae verticillatae,
Radix Calystegiae sepii, Radix Glycyrrhizae Preparata are ground into coarse powder, the water soaking of 7 times of weight portions of addition 3-4 hour, decoct 1-2 hour, filter is collected by filtration
Liquid, filtering residue adds water as 5 times of medical material weight portion decoctions 1-1.5 hour, collecting decoction, filters, and filtrate reduced in volume is to the closeest
Degree is 1.10 (60 DEG C of surveys), adds ethanol and makes alcohol content reach 45%, stand 12 hours, filters, filtrate recycling ethanol, be concentrated into 60
DEG C recording relative density is 1.16, uses spray drying method to make granule, loads capsule shells and get final product after granulate, sterilizing.This enforcement
Capsule every loading amount 0.3g, is equivalent to crude drug 0.8g.
Embodiment 3 capsule
Prescription: Cortex Araliae Elatae Radicis 15 parts, Caulis et Folium Fici beecheyanae 25 parts, Rhizoma Corydalis Decumbentis 10 parts, Herba Agrimoniae 8 parts, Rhizoma Curcumae 12 parts, Rhizoma alcasiae odorae 7 parts, mountain are kind
12 parts of mushroom, Radix litseae verticillatae 12 parts, Radix Calystegiae sepii 12 parts, Radix Glycyrrhizae Preparata 8 parts.
Preparation method: by prescription take Cortex Araliae Elatae Radicis, Caulis et Folium Fici beecheyanae, Rhizoma Corydalis Decumbentis, Herba Agrimoniae, Rhizoma Curcumae, Rhizoma alcasiae odorae, Pseudobulbus Cremastrae Seu Pleiones, Radix litseae verticillatae,
Radix Calystegiae sepii, Radix Glycyrrhizae Preparata are ground into coarse powder, the water soaking of 8 times of weight portions of addition 3-4 hour, decoct 1-2 hour, filter is collected by filtration
Liquid, filtering residue adds water as 5 times of medical material weight portion decoctions 1-1.5 hour, collecting decoction, filters, and filtrate reduced in volume is to the closeest
Degree is 1.09 (60 DEG C of surveys), adds ethanol and makes alcohol content reach 40-50% (preferably 45%), stand 12 hours, filters, and filtrate is reclaimed
Ethanol, being concentrated into 60 DEG C and recording relative density is 1.20, uses spray drying method to make granule, loads capsule after granulate, sterilizing
Shell and get final product.Every loading amount 0.33g of this enforcement capsule, is equivalent to crude drug 1.0g.
Embodiment 4 capsule
Prescription: Cortex Araliae Elatae Radicis 10 parts, Caulis et Folium Fici beecheyanae 20 parts, Rhizoma Corydalis Decumbentis 10 parts, Herba Agrimoniae 7 parts, Rhizoma Curcumae 7 parts, Rhizoma alcasiae odorae 8 parts, mountain are kind
8 parts of mushroom, Radix litseae verticillatae 12 parts, Radix Calystegiae sepii 9 parts, Radix Glycyrrhizae Preparata 6 parts.
Preparation method: by prescription take Cortex Araliae Elatae Radicis, Caulis et Folium Fici beecheyanae, Rhizoma Corydalis Decumbentis, Herba Agrimoniae, Rhizoma Curcumae, Rhizoma alcasiae odorae, Pseudobulbus Cremastrae Seu Pleiones, Radix litseae verticillatae,
Radix Calystegiae sepii, Radix Glycyrrhizae Preparata are ground into coarse powder, the water soaking of 6 times of weight portions of addition 3-4 hour, decoct 1-2 hour, filter is collected by filtration
Liquid, filtering residue adds water as 5 times of medical material weight portion decoctions 1-1.5 hour, collecting decoction, filters, and filtrate reduced in volume is to the closeest
Degree is 1.06 (60 DEG C of surveys), adds ethanol and makes alcohol content reach 46%, stand 12 hours, filters, filtrate recycling ethanol, be concentrated into 60
DEG C recording relative density is 1.16, uses spray drying method to make granule, loads capsule shells and get final product after granulate, sterilizing.
Embodiment 5 capsule
Prescription: Cortex Araliae Elatae Radicis 15 parts, Caulis et Folium Fici beecheyanae 20 parts, Rhizoma Corydalis Decumbentis 12 parts, Herba Agrimoniae 8 parts, Rhizoma Curcumae 8 parts, Rhizoma alcasiae odorae 6 parts, mountain are kind
10 parts of mushroom, Radix litseae verticillatae 17 parts, Radix Calystegiae sepii 13 parts, Radix Glycyrrhizae Preparata 8 parts.
Preparation method: by prescription take Cortex Araliae Elatae Radicis, Caulis et Folium Fici beecheyanae, Rhizoma Corydalis Decumbentis, Herba Agrimoniae, Rhizoma Curcumae, Rhizoma alcasiae odorae, Pseudobulbus Cremastrae Seu Pleiones, Radix litseae verticillatae,
Radix Calystegiae sepii, Radix Glycyrrhizae Preparata are ground into coarse powder, the water soaking of 5 times of weight portions of addition 3-4 hour, decoct 1-2 hour, filter is collected by filtration
Liquid, filtering residue adds water as 6 times of medical material weight portion decoctions 1-1.5 hour, collecting decoction, filters, and filtrate reduced in volume is to the closeest
Degree is 1.08 (60 DEG C of surveys), adds ethanol and makes alcohol content reach 50%, stand 12 hours, filters, filtrate recycling ethanol, be concentrated into 60
DEG C recording relative density is 1.17, uses spray drying method to make granule, loads capsule shells and get final product after granulate, sterilizing.
Embodiment 6 capsule
Prescription: Cortex Araliae Elatae Radicis 12 parts, Caulis et Folium Fici beecheyanae 25 parts, Rhizoma Corydalis Decumbentis 8 parts, Herba Agrimoniae 6 parts, Rhizoma Curcumae 10 parts, Rhizoma alcasiae odorae 8 parts, mountain are kind
8 parts of mushroom, Radix litseae verticillatae 12 parts, Radix Calystegiae sepii 12 parts, Radix Glycyrrhizae Preparata 5 parts.
Preparation method: by prescription take Cortex Araliae Elatae Radicis, Caulis et Folium Fici beecheyanae, Rhizoma Corydalis Decumbentis, Herba Agrimoniae, Rhizoma Curcumae, Rhizoma alcasiae odorae, Pseudobulbus Cremastrae Seu Pleiones, Radix litseae verticillatae,
Radix Calystegiae sepii, Radix Glycyrrhizae Preparata are ground into coarse powder, the water soaking of 7 times of weight portions of addition 3-4 hour, decoct 1-2 hour, filter is collected by filtration
Liquid, filtering residue adds water as 5 times of medical material weight portion decoctions 1-1.5 hour, collecting decoction, filters, and filtrate reduced in volume is to the closeest
Degree is 1.09 (60 DEG C of surveys), adds ethanol and makes alcohol content reach 45%, stand 12 hours, filters, filtrate recycling ethanol, be concentrated into 60
DEG C recording relative density is 1.18, uses spray drying method to make granule, loads capsule shells and get final product after granulate, sterilizing.
Embodiment 7 capsule
Prescription: Cortex Araliae Elatae Radicis 12 parts, Caulis et Folium Fici beecheyanae 22 parts, Rhizoma Corydalis Decumbentis 13 parts, Herba Agrimoniae 6 parts, Rhizoma Curcumae 8 parts, Rhizoma alcasiae odorae 10 parts, mountain are kind
10 parts of mushroom, Radix litseae verticillatae 13 parts, Radix Calystegiae sepii 8 parts, Radix Glycyrrhizae Preparata 6 parts.
Preparation method: by prescription take Cortex Araliae Elatae Radicis, Caulis et Folium Fici beecheyanae, Rhizoma Corydalis Decumbentis, Herba Agrimoniae, Rhizoma Curcumae, Rhizoma alcasiae odorae, Pseudobulbus Cremastrae Seu Pleiones, Radix litseae verticillatae,
Radix Calystegiae sepii, Radix Glycyrrhizae Preparata are ground into coarse powder, the water soaking of 6 times of weight portions of addition 3-4 hour, decoct 1-2 hour, filter is collected by filtration
Liquid, filtering residue adds water as 6 times of medical material weight portion decoctions 1-1.5 hour, collecting decoction, filters, and filtrate reduced in volume is to the closeest
Degree is 1.09 (60 DEG C of surveys), adds ethanol and makes alcohol content reach 45%, stand 12 hours, filters, filtrate recycling ethanol, be concentrated into 60
DEG C recording relative density is 1.16, uses spray drying method to make granule, loads capsule shells and get final product after granulate, sterilizing.
Embodiment 8 capsule
Prescription: Cortex Araliae Elatae Radicis 12 parts, Caulis et Folium Fici beecheyanae 20 parts, Rhizoma Corydalis Decumbentis 10 parts, Herba Agrimoniae 9 parts, Rhizoma Curcumae 12 parts, Rhizoma alcasiae odorae 11 parts, mountain
Rhizoma sagittariae sagittifoliae 7 parts, Radix litseae verticillatae 15 parts, Radix Calystegiae sepii 12 parts, Radix Glycyrrhizae Preparata 8 parts.
Preparation method: by prescription take Cortex Araliae Elatae Radicis, Caulis et Folium Fici beecheyanae, Rhizoma Corydalis Decumbentis, Herba Agrimoniae, Rhizoma Curcumae, Rhizoma alcasiae odorae, Pseudobulbus Cremastrae Seu Pleiones, Radix litseae verticillatae,
Radix Calystegiae sepii, Radix Glycyrrhizae Preparata are ground into coarse powder, the water soaking of 8 times of weight portions of addition 3-4 hour, decoct 1-2 hour, filter is collected by filtration
Liquid, filtering residue adds water as 5 times of medical material weight portion decoctions 1-1.5 hour, collecting decoction, filters, and filtrate reduced in volume is to the closeest
Degree is 1.12 (60 DEG C of surveys), adds ethanol and makes alcohol content reach 40-50% (preferably 45%), stand 12 hours, filters, and filtrate is reclaimed
Ethanol, being concentrated into 60 DEG C and recording relative density is 1.15, uses spray drying method to make granule, loads capsule after granulate, sterilizing
Shell and get final product.
Embodiment 9 toxicological experiment
(1) acute toxicity testing: choose kunming mice 40, male and female half and half, body weight 28～38g, be randomly divided into four groups,
I.e. matched group and administration group, before experiment, fasting 12 hours, is dissolved in water by Chinese medicine capsules prepared by embodiments of the invention 1-3
In make suspension (concentration is 6.5g-6.6g crude drug/ml, maximum concentration) gavage, gavage volume is 5ml/kg, and matched group gives
Normal saline, one day be administered 2 times, delivery time 6 hours, Continuous Observation 14 days after administration, and record mice
Toxic reaction and death toll.
Test result indicate that: compare with matched group, after administration, each group mice has no notable difference, tests Continuous Observation 14
My god, mouse systemic situation, diet, drinking-water, body weight increase the most normal.The capsule i.e. LD50 ＞ of the Mouse oral gavage present invention
32.5-33.0g crude drug/kg, every day, maximum dosage-feeding was 66.0g crude drug/kg/ day.Therefore the Chinese medicine acute toxicity pole of the present invention
Low, clinical drug safety.
(2) long term toxicity test: mice is pressed 1.2,2.4 and 4.8g crude drugs/kg by Chinese medicine embodiment 1 capsule of the present invention
After 15 weeks (1.0ml/100g body weight, every day 2 times) of continuous use and drug withdrawal 3 weeks, result shows: the Chinese medicine of the present invention hair to mice
Send out, behavior, defecation, body weight, organ weights, hemogram, hepatic and renal function, blood glucose, the index such as blood fat all have no significant effect, internal organs meat
Eye does not find that difference change and histological indications show, after medication 15 weeks and drug withdrawal 3 weeks, Organs of Mice is all without obvious
Change.Illustrate that Chinese medicine of the present invention is little to toxicity after mice long-term prescription, after drug withdrawal, also there is no difference reaction, application safety.
The clinical observation test of embodiment 10 medicine of the present invention syndrome of qi stagnation and blood stasis postoperative to thyroid carcinoma patient
1 data and method
1.1 physical data: choose in December, 2012 in December ,-2013 and be in hospital in the court medical Operation of Thyroid Carcinoma patient
89 examples, male 29 examples, female 60 example；Age 24～57 years old；Art formula includes that Ipsilateral gland leaf excision+isthmus excision+central lymph node is clear
Sweep art 36 example, bilateral gland lobectomy+Functional Neck Dissection 53 example.All cases is examined by histology or pathology
Look into and make a definite diagnosis, wherein papillary carcinoma 72 example, filter blocking cancer 17 example.
Random digits table is used to be randomly divided into treatment group and matched group.Treatment group 45 example, male 15 examples, female 30 example；Averagely
Year at age (36.6 ± 9.4)；Matched group 44 example, male 14 examples, female 30 example；Year mean age (35.8 ± 9.1)；Two groups of anticipated existence
Phase is all higher than 6 months, and two groups of no significant difference (P ＞ 0.05) at aspects such as sex, age, pathology, having can
Compare property.
1.2 diagnostic criterias:
1.2.1 diagnosis of thyroid cancer standard: make a definite diagnosis through preoperative B ultrasonic, thyroid radioisotope scanning or needle biopsy, and
It is diagnosed as thyroid carcinoma through verified by postoperative pathology；Accompany or without abnormal thyroid function.
1.2.2 Chinese medical discrimination is with reference to " new Chinese medicine guideline of clinical investigations " and China Association of Traditional Chinese Medicine such as Zheng Xiao cornels
" Traditional Chinese Medicine Constitution Classification and judge " drafts tcm diagnosis standard as syndrome of qi stagnation and blood stasis,
Primary symptom: spiritlessness and weakness, deficiency of QI with disinclination to talk, spontaneous perspiration is susceptible, and dizzy margins of eyelids, neck and shoulder part swelling twinges, aversion to cold and cold limbs.
Double disease: lusterless complexion or dark and gloomy, the heart uncomfortable in chest, neck shoulder numbness, urine frequency is the most, loose stool or constipation.
No arteries and veins: light red tongue is dim or has purpura, sublingual vessel is purple dim or increases thick, deep and hesitant pulse.Tcm symptom is marked: asymptomatic meter 0
Point, slight meter 1 point, moderate meter 2 points, severe meter 3 points, tongue arteries and veins is not scored.
1.3 case exclusion standards: gestation, women breast-feeding their children, abnormal liver function person；It is associated with cardiovascular, liver, kidney and hemopoietic
The severe primary diseases such as system, psychotic；Accept other Chinese medicines, glucocorticoid and other immunosuppressant treatment
Person.
1.4 Therapeutic Method:
Matched group: give levothyroxine sodium tables treatment, adjust dosage according to thyroid function.Treatment group: at matched group
Add on the basis for the treatment of with the embodiment of the present invention 1 preparation capsule for treating, twice on the one, each 3-5 grain.Two groups all with January for 1
The course for the treatment of, after terminating 3 courses for the treatment of, carry out observation of curative effect.
1.5 observation index:
1.5.1 Elityran TG is measured before and after treatment；
1.5.2 observe spiritlessness and weakness, deficiency of QI with disinclination to talk, spontaneous perspiration margins of eyelids susceptible, dizzy, neck and shoulder part swelling twinge, tongue fur pulse condition
Etc. the change of qi depression to blood stasis syndrome, the syndrome score before record treatment and after treatment respectively.
1.5.2 Evaluation on quality of life: using Karnofsky standards of grading, it is effective that Ka Shi scoring improves more than 20 points, carries
High 10-20 is divided into effectively, improve 10 points be stable down to declining within 10 points, declining more than 10 points is deterioration.
1.6 efficacy assessment standards: comprehensive therapeutic effect criterion: computing formula: (integration after integration-treatment before treatment)/control
Integration before treating, is expressed as a percentage.Recovery from illness: symptom and sign disappears substantially, integration is more than or equal to 90%；Effective: symptom and sign
Being obviously improved, integration is more than or equal to 75%；Effective: symptom and sign take a favorable turn, integration is more than or equal to 35%；Invalid: symptom
Sign is not improved, even increase the weight of, integration is less than 35%.
1.7 statistical analysis use spss16.0 statistical software to be analyzed, and the comparison of enumeration data two sample rate uses
X2Inspection, measurement data withRepresent, compare before and after treatment with paired t-test, between group, compare employing t inspection, P ＜ 0.05 table
Differential is different statistically significant.
2 results
After 2.1 treatments, two groups of patient clinical comprehensive therapeutic effects compare: after 3 courses for the treatment of, and treatment group cures 14 examples, effective 21 examples,
Effective 8 examples, invalid 2 examples, total effective rate 95.6%；And matched group cures 6 examples, effective 10 examples, effective 18 examples, invalid 10 examples, always
Effective percentage 77.2%, the therapeutic effect for the treatment of group is substantially better than matched group, difference statistically significant (P ＜ 0.01).It is shown in Table 1.
Two groups of patient clinical comparitive study after table 1 treatment, example (%)
Note: matched group compares, * P ＜ 0.01.
Before and after 2.2 liang of group treatments, syndrome total mark compares: after two groups of treatments, syndrome integral all significantly improves, ratio front with treatment
Relatively difference all has significant (P ＜ 0.05, P ＜ 0.01)；Comparing between two groups after treatment, treatment group disease total mark reduces
Less, difference also has statistics meaning (P ＜ 0.05)..It is shown in Table 2.
Before and after the group treatment of 2 liang of table, disease total mark comparesPoint)
Note: compare with treatment, * P ＜ 0.05, * * P ＜ 0.01；Compare between group,#P ＜ 0.05.
Main syndromes integral contrast before and after 2.3 liang of group treatments: spiritlessness and weakness after two groups of treatments, deficiency of QI with disinclination to talk, spontaneous perspiration is susceptible
Integration all significantly improves, and compares before treatment, and difference all has significant (P ＜ 0.05, P ＜ 0.01)；Treatment group dizziness mesh
String, neck and shoulder part swelling twinges integration and all significantly improves, and comparing difference front with treatment all has significant (P ＜ 0.01)；And it is right
According to the front comparing difference not statistically significant of group and treatment.After treatment, two groups are compared, and difference also has significant (P ＜ 0.05).
It is shown in Table 3.
Main disease integral contrast before and after the group treatment of 3 liang of table (Point)
Note: compare with before group treatment, * P ＜ 0.05, * * P ＜ 0.01；Compare between group after treatment,#P ＜ 0.05.
2.4 liang of group Evaluation on quality of lifes compare: effective 12 examples for the treatment of group, effective 21 examples, stablize 10 examples, deteriorate 2 examples, always have
Efficiency 95.6%；And effective 5 examples of matched group, effective 14 examples, to stablize 17 examples, deteriorate 8 examples, total effective rate 81.8%, treatment group is suffered from
The quality of life of person improves situation and is substantially better than matched group, difference statistically significant (P ＜ 0.05).It is shown in Table 4.
After the group treatment of 4 liang of table, Evaluation on quality of life compares
Note: matched group compares, * P ＜ 0.05.
The change of TG value before and after 2.5 liang of group treatments: TG value comparing difference not statistically significant before two groups of treatments, has comparable
Property.After treatment, treatment group TG value is obviously reduced, with treatment before comparing difference statistically significant (P ＜ 0.05), matched group with control
Compare before treatment, no significant difference, compare between two groups after treatment, difference statistically significant (P ＜ 0.05), treatment group TG
What value reduced becomes apparent from.It is shown in Table 5.
The change of TG value before and after the group treatment of 5 liang of table, (ug/L)
Note: compare with treatment, * P ＜ 0.05；Compare between group,#P ＜ 0.05.
2.6 untoward reaction and safety detection: treatment group during observing, FT3、FT4And TSH there is no significant change, explanation
Chinese medicine composition is the least for the function effect of thyroid gland hormone, and treatment group patient is without any subjective uncomfortable, blood, urine, big
Just conventional and the heart, Liver and kidney function etc. check exception all do not occur.
This result of study shows, thyroid carcinoma is postoperative significantly improves trouble for the treatment of the present invention medication combined levothyroxine sodium
The tcm clinical practice symptom of person, improves Ka Shi scoring, improves the quality of living；To the suppression secretion of human thyrotropin, reduction
TG has certain trend, is one safely and effectively auxiliary treating method, and clinic is worthy to be popularized.
Claims (10)
1. the pharmaceutical preparation treating the postoperative syndrome of qi stagnation and blood stasis of thyroid carcinoma, it is characterised in that by Cortex Araliae Elatae Radicis, Caulis et Folium Fici beecheyanae, summer
Nothing, Herba Agrimoniae, Rhizoma Curcumae, Rhizoma alcasiae odorae, Pseudobulbus Cremastrae Seu Pleiones, Radix litseae verticillatae, Radix Calystegiae sepii, Radix Glycyrrhizae Preparata are that medicinal raw material is made.
2. the pharmaceutical preparation treating the postoperative syndrome of qi stagnation and blood stasis of thyroid carcinoma as claimed in claim 1, it is characterised in that by following
The Medicinal crude drug of weight is made: Cortex Araliae Elatae Radicis 10-15 part, Caulis et Folium Fici beecheyanae 20-25 part, Rhizoma Corydalis Decumbentis 8-13 part, Herba Agrimoniae 6-9
Part, Rhizoma Curcumae 7-12 part, Rhizoma alcasiae odorae 6-11 part, Pseudobulbus Cremastrae Seu Pleiones 7-12 part, Radix litseae verticillatae 12-17 part, Radix Calystegiae sepii 8-13 part, Radix Glycyrrhizae Preparata 5-8 part.
3. the pharmaceutical preparation treating the postoperative syndrome of qi stagnation and blood stasis of thyroid carcinoma as claimed in claim 2, it is characterised in that by following
The Medicinal crude drug of weight is made: Cortex Araliae Elatae Radicis 12 parts, Caulis et Folium Fici beecheyanae 25 parts, Rhizoma Corydalis Decumbentis 12 parts, Herba Agrimoniae 8 parts, Rhizoma Curcumae 10
Part, Rhizoma alcasiae odorae 9 parts, Pseudobulbus Cremastrae Seu Pleiones 12 parts, Radix litseae verticillatae 15 parts, Radix Calystegiae sepii 10 parts, Radix Glycyrrhizae Preparata 6 parts.
4. the pharmaceutical preparation of the postoperative syndrome of qi stagnation and blood stasis for the treatment of thyroid carcinoma as described in claim 1-3 is arbitrary, it is characterised in that
Described pharmaceutical preparation can by Cortex Araliae Elatae Radicis, Caulis et Folium Fici beecheyanae, Rhizoma Corydalis Decumbentis, Herba Agrimoniae, Rhizoma Curcumae, Rhizoma alcasiae odorae, Pseudobulbus Cremastrae Seu Pleiones, Radix litseae verticillatae, Radix Calystegiae sepii, process
Radix Glycyrrhizae or its water or its extractive with organic solvent are active component, are prepared from according to routine techniques.
5. the pharmaceutical preparation of the postoperative syndrome of qi stagnation and blood stasis for the treatment of thyroid carcinoma as described in claim 1-4 is arbitrary, it is characterised in that
Described pharmaceutical preparation is preferably made as peroral dosage form.
6. the pharmaceutical preparation treating the postoperative syndrome of qi stagnation and blood stasis of thyroid carcinoma as claimed in claim 5, it is characterised in that described mouth
Oral dosage form is preferably capsule, tablet, granule, pill, powder, sublimed preparation, unguentum, etc..
7. the pharmaceutical preparation of the postoperative syndrome of qi stagnation and blood stasis for the treatment of thyroid carcinoma as described in claim 6 is arbitrary, it is characterised in that institute
State peroral dosage form and be preferably capsule, tablet, granule.
8. the pharmaceutical preparation of the postoperative syndrome of qi stagnation and blood stasis for the treatment of thyroid carcinoma as described in claim 7 is arbitrary, it is characterised in that institute
State peroral dosage form and be preferably capsule.
9. the pharmaceutical preparation of the postoperative syndrome of qi stagnation and blood stasis for the treatment of thyroid carcinoma as described in claim 1-8 is arbitrary, it is characterised in that
The preparation method of described capsule comprises the steps: to take Cortex Araliae Elatae Radicis, Caulis et Folium Fici beecheyanae, Rhizoma Corydalis Decumbentis, Herba Agrimoniae, Rhizoma Curcumae, sea by prescription
Taro, Pseudobulbus Cremastrae Seu Pleiones, Radix litseae verticillatae, Radix Calystegiae sepii, Radix Glycyrrhizae Preparata are ground into coarse powder, the water soaking of 3-10 times of weight portion of addition 3-4 hour, decoct
1-2 hour, filtrate being collected by filtration, add water as medical material weight portion 3-6 times of filtering residue decocts 1-1.5 hour, and collecting decoction filters,
Filtrate reduced in volume to relative density is 1.06-1.12 (60 DEG C of survey), adds ethanol and makes alcohol content reach 40-50% (preferably
45%), standing 12 hours, filter, filtrate recycling ethanol, being concentrated into 60 DEG C and recording relative density is 1.15-1.20, uses spraying
Seasoning makes granule, loads capsule shells and get final product after granulate, sterilizing.
10. the arbitrary described pharmaceutical preparation of claim 1-3 is in preparation treatment thyroid carcinoma postoperative syndrome of qi stagnation and blood stasis medicine
Purposes.
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| CN107469003A (en) * | 2017-09-07 | 2017-12-15 | 成都兴倍加生物科技有限责任公司 | A kind of endo-medicine and preparation method for treating the postoperative syndrome of qi stagnation and blood stasis of thyroid cancer |
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| Title |
|---|
| 谷言芳等: "《谷铭三治疗肿瘤经验集》", 28 February 2002, 上海科学技术出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107469003A (en) * | 2017-09-07 | 2017-12-15 | 成都兴倍加生物科技有限责任公司 | A kind of endo-medicine and preparation method for treating the postoperative syndrome of qi stagnation and blood stasis of thyroid cancer |
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