CN106668664A

CN106668664A - Medicine for treating primary thrombocythemia and preparation method thereof

Info

Publication number: CN106668664A
Application number: CN201710153177.9A
Authority: CN
Inventors: 常德凤
Original assignee: Individual
Current assignee: Individual
Priority date: 2017-03-15
Filing date: 2017-03-15
Publication date: 2017-05-17

Abstract

The invention discloses a medicine for treating primary thrombocythemia and a preparation method thereof. The medicine is prepared from the following raw materials according to a certain weight proportion: dried rehmannia root, radix scrophulariae, ligusticum wallichii, red peony root, safflower, rhizoma sparganii, peach kernels, leech, artemisia capillaries, jasmine, mangnolia officinalis, honeysuckle flowers, rhizoma anemarrhenae, moutan barks, leonurus, lithospermum, puerarin, ramulus mori, polygonum multiflorum, rhizoma bletillae and colla corii asini. The medicine disclosed by the invention has the functions of cooling blood, nourishing yin, promoting secretion of saliva or body fluid, clearing heat, activating blood circulation, tonifying the liver and the kidney and nourishing blood. The medicine used for treating the primary thrombocythemia can quickly become effective, has an excellent curative effect and is capable of preventing relapse.

Description

It is a kind of to treat medicine of primary thrombocytosiss and preparation method thereof

Technical field

The present invention relates to a kind of treat medicine of primary thrombocytosiss and preparation method thereof, belong to the field of Chinese medicines.

Background technology

Primary thrombocytosiss are one kind of one group of relatively chronic myeloproliferative diseases, also referred to as " bleeding Property ", " true property " or " idiopathic " thrombocytosiss.Similar to other myeloproliferative diseases, this disease is thin for multipotency Hematopoietic Stem Born of the same parents clone disease.Megalokaryocyte paraplasm in bone marrow is characterized as, platelet count is significantly raised.Main clinical manifestation is bleeding And thrombophilia.Due to western medicine large side effects, therefore people are in effectively treatment primary thrombocytosiss There is great demand in medicine medicine, up to now, it has not been found that with regard to the relevant report of the present invention.

The content of the invention

The present inventor have found effectively treatment primary finally according to the checking repeatedly of research and the clinical trial of theory of Chinese medical science The medicine of property thrombocytosiss, so as to complete the present invention.

It is an object of the invention to provide a kind of Chinese medicine composition of effectively treatment primary thrombocytosiss.

Another object of the present invention just there is provided the preparation method of the Chinese medicine composition.

Medicine of the present invention is to select Radix Rehmanniae, Radix Scrophulariae, Rhizoma Chuanxiong, Radix Paeoniae Rubra, Flos Carthami, Rhizoma Sparganii, Semen Persicae, Hirudo, Herba Artemisiae Scopariae, Cape jasmine Son, Cortex Magnoliae Officinalis, Flos Lonicerae, the Rhizoma Anemarrhenae, Cortex Moutan, Herba Leonuri, Radix Arnebiae (Radix Lithospermi), Radix Puerariae, Ramulus Mori, Radix Polygoni Multiflori, Pseudobulbus Bletillae (Rhizoma Bletillae), Colla Corii Asini are combined preparation , cause each efficacy of drugs to produce synergism these drug regimens such that it is able to effectively treatment idiopathic thrombocythemia Disease.Wherein it is because that its nature and flavor is sweet from Radix Rehmanniae, trembles with fear, GUIXIN, liver and kidney channel has clearing away heat and cooling blood, and yin nourishing, the function of promoting the production of body fluid is controlled Pyreticosis polydipsia, yin asthenia generating intrinsic heat, hectic fever due to YIN-deficiency consumptive fever, Heat Diabetes is spitted blood, epistaxis, spot dermexanthesis.Its nature and flavor is because from Radix Scrophulariae Hardship, it is salty, it is cool, enter lung, kidney channel, there is YIN nourishing, pathogenic fire reducing, relieving restlessness, the function of removing toxic substances controls pyreticosis polydipsia, sends out speckle, and hectic fever due to YIN-deficiency consumptive fever, night sleeps It is not peaceful, spontaneous sweating, Tianjin hinder constipation, hematemesis and epistaxiss, laryngopharynx swelling and pain, carbuncle, scrofula.It is because that its nature and flavor is pungent from Rhizoma Chuanxiong, temperature, Enter liver, gallbladder meridian, there is activating QI to alleviate the depression, and dispeiling pathogenic wind and removing dampness, the function of promoting blood circulation and stopping pain is controlled air-cooled headache rotation and swooned, hypochondriac pain abdomen pain, arthralgia due to cold muscle Contraction, amenorrhea, difficult labour, postpartum stagnation block pain, ulcer sores.It is because that its nature and flavor is bitter from Radix Paeoniae Rubra, is slightly cold, return liver warp has heat clearing away Removing heat from blood, the function of eliminating stasis to stop pain is controlled warm poison and is gone mad, hematemesis and epistaxiss, conjunctival congestion and swelling pain, hypochondriac pain due to stagnation of liverQI, amenorrhea dysmenorrhea , Epilepsy abdominal mass stomachache, Injury from falling down, carbuncle swells sore.It is because that its nature and flavor is pungent from Flos Carthami, temperature, enter the heart, Liver Channel have promoting blood circulation to restore menstrual flow, the work(of blood stasis removing pain relieving Can, controlling through closing , mass in the abdomen, difficult labour, stillborn fetuses, disease that postpartum lochia can't go, blood stasis are had a pain, carbuncle, injury from falling down.It is because from Rhizoma Sparganii Nature and flavor toil, puts down, enter liver, spleen channel, there is removing blood stasis, and circulation of qi promoting, removing food stagnancy, the function , Zhi lumps in the chest and abdomen of pain relieving, QI and blood coagulates band, trusted subordinate's pain Bitterly, swollen pain under the side of body, amenorrhea, postnatal blood stasis stomachache, traumatic injury, sore swells are hard.Its nature and flavor bitter sweet is because from Semen Persicae, is put down, Enter the heart, liver, large intestine channel, there is blood stasis removing and clots absorbing, moisturize the function of sliding Jing, controlling through closing , mass in the abdomen, calentura blood-retention, arthralgia due to stagnation of blood, malaria, traumatic injury Damage, swelling and pain due to blood stasis, the dry constipation of blood.The salty hardship of its nature and flavor is because from Hirudo, is put down, poisonous, enter liver, bladder warp there are removing blood stasis, by The stasis of blood, the function of stimulating the menstrual flow controls blood-retention , mass in the abdomen, accumulation, women's amenorrhea, and blood stasis are into consumptive disease, injury from falling down, conjunctival congestion with ophthalmalgia, nebula.From mattress Herba Artemisiae Scopariae is because its nature and flavor toil, cool, enter liver, spleen, bladder warp, the function of having clearing away heat-damp and promoting diuresis, controls jaundice due to damp-heat, dysuria, Pruritus due to wind pathogen sore scabies.It is because that its nature and flavor is bitter from Fructus Gardeniae, trembles with fear, enter the heart, liver, lung, stomach has heat clearing away, and pathogenic fire purging, the function of removing heat from blood is controlled Calentura restlessness of asrhenia type and insomnia, jaundice, gonorrhea is quenched one's thirst, conjunctival congestion, pharyngalgia, is spitted blood, and epistaxis, dysentery, hematuria, pathopyretic ulcer is sprained and swollen and ache. Its nature and flavor toil is because from Cortex Magnoliae Officinalis, temperature enters spleen, stomach, large intestine channel, there is warming middle-JIAO, and the therapeutic method to keep the adverse QI flowing downwards, dampness, the function of expectorant controls chest and abdomen Feeling of fullness distending pain, regurgitation, vomiting, dyspepsia does not disappear, phlegm and retained fluid is breathed with cough, cold-damp dysentery.It is because that its nature and flavor is sweet from Flos Lonicerae, trembles with fear, enters Lung, stomach, there is heat clearing away, and the function of removing toxic substances controls warm disease heating, toxic-heat and blood stasis, carbuncle and ulcer, toxic swelling, scrofula, anal fistula.It is from the Rhizoma Anemarrhenae Because its nature and flavor is bitter, tremble with fear, enter lung, stomach, kidney channel, there is nourishing YIN to lower pathogenic fire, the function of moisturize laxation is controlled dysphoria with smothery sensation and quenched one's thirst, hectic fever due to YIN-deficiency consumptive fever, lung Heat cough, constipation due to dry stool, dysuria.It is because that its nature and flavor is worked hard from Cortex Moutan, cool, enter the heart, liver and kidney channel have heat clearing away, cool Blood, and blood, the function of repercussive, control the pathogenic heat attacking blood system in febrile diseases, send out speckle , Jing Epilepsy, tell, be defeated in battle, have blood in stool, and hectic fever due to YIN-deficiency consumptive fever, amenorrhea , mass in the abdomen, carbuncle and ulcer is flutterred Damage.It is because that its nature and flavor is worked hard from Herba Leonuri, it is cool, enter pericardium, Liver Channel, there is promoting blood circulation, blood stasis dispelling, regulating menstruation, the function of the water that disappears controls the moon Jing is uncomfortable, controls and Lou has difficult labour, and retention of placenta, puerperal blood faintss, abdominal pain due to blood stasis, metrorrhagia and metrostaxises, hematuria rushes down blood, carbuncle swells sore.From purple Grass is because its nature and flavor earnestly, trembles with fear, and enters percardium, Liver Channel, there is removing heat from blood, invigorates blood circulation, and the function of heat-clearing and toxic substances removing controls warm macule, wet Hot jaundice, purpura tells, is defeated in battle, hematuria, stranguria with turbid discharge, dysentery, constipation with heat retention, burn, eczema, erysipelas, carbuncle and ulcer.It is because from Radix Puerariae Its nature and flavor is sweet pungent, puts down, and enters spleen, stomach, there is yang invigorating expelling pathogenic factors from muscles, and rash antidiarrheal, the function that relieving restlessness is only drunk controls typhoid fever, controls typhoid fever, warms Headache stiffness of the nape, dysphoria with smothery sensation is quenched one's thirst, is had loose bowels, and dysentery, skin eruption is impermeable, hypertension, angina pectoriss, deaf.Its nature and flavor is because from Ramulus Mori Hardship, puts down, and enters Liver Channel, there is wind-damp dispelling, and sharp joint, the function of water-filling gas controls anemofrigid-damp arthralgia, spasm of the limbs, beriberi edema, human body wind Itch.It is because that its nature and flavor bitter sweet is puckery from Radix Polygoni Multiflori, tepor enters liver and kidney channel, there is tonifying liver, kidney tonifying, blood-nourishing, the function of wind-dispelling is controlled Hepatic and renal YIN deficiency, sending out must be early white, and blood deficiency is dizzy, and waist and knee is weak, and muscles and bones is ached, and passes out semen, metrorrhagia and leukorrhagia, chronic malaria, chronic dysentery, chronic hepatitiss, carbuncle It is swollen, scrofula, hemorrhoidal hamorrhage, haemorrhoids.Its nature and flavor bitter sweet is because from Pseudobulbus Bletillae (Rhizoma Bletillae), it is cool, enter lung meridian, there is tonifying the lung, to stop blooding, detumescence is raw to see, and holds back The function of skin ulcer, controls lung and hinders hemoptysis, epistaxis, incised wound bleeding, swollen ulcer drug, canker sores, soup fire burn, rhagadia manus et pedis.From Ah Glue is because that its nature and flavor is sweet, puts down, and enters lung, liver and kidney channel, there is a nourishing YIN and supplementing blood, antiabortive function, controls blood deficiency, cough due to consumptive disease, spit blood, Epistaxis, have blood in stool, menoxenia, metrorrhagia, vaginal bleeding during pregnancy.

Specific embodiment

The drug dose of instant component is also that inventor summarizes what is drawn through groping in a large number, and the consumption of each component is following heavy All there is preferable curative effect in the range of amount：

25-35 gram of Radix Rehmanniae, 25-35 gram of Radix Scrophulariae, 10-20 gram of Rhizoma Chuanxiong, 10-20 gram of Radix Paeoniae Rubra, 10-20 gram of Flos Carthami, 5-15 gram of Rhizoma Sparganii, 5-15 gram of Semen Persicae, 4-8 gram of Hirudo, 25-35 gram of Herba Artemisiae Scopariae, 10-20 gram of Fructus Gardeniae, Cortex Magnoliae Officinalis 4-8 gram, 25-35 gram of Flos Lonicerae, Rhizoma Anemarrhenae 5- 15 grams, 10-20 gram of Cortex Moutan, 15-25 gram of Herba Leonuri, 15-25 gram of Radix Arnebiae (Radix Lithospermi), 5-15 gram of Radix Puerariae, 15-25 gram of Ramulus Mori, Radix Polygoni Multiflori 5- 15 grams, 5-15 gram of Pseudobulbus Bletillae (Rhizoma Bletillae), 4-8 gram of Colla Corii Asini.

Preferably：

30 grams of Radix Rehmanniae, 30 grams of Radix Scrophulariae, 15 grams of Rhizoma Chuanxiong, 15 grams of Radix Paeoniae Rubra, 15 grams of Flos Carthami, 10 grams of Rhizoma Sparganii, 10 grams of Semen Persicae, 6 grams of Hirudo, 30 grams of Herba Artemisiae Scopariae, 15 grams of Fructus Gardeniae, 6 grams of Cortex Magnoliae Officinalis, 30 grams of Flos Lonicerae, 10 grams of the Rhizoma Anemarrhenae, 15 grams of Cortex Moutan, 20 grams of Herba Leonuri, Radix Arnebiae (Radix Lithospermi) 20 Gram, 10 grams of Radix Puerariae, 20 grams of Ramulus Mori, 10 grams of Radix Polygoni Multiflori, 10 grams of Pseudobulbus Bletillae (Rhizoma Bletillae), 6 grams of Colla Corii Asini.

The preparation method of medicine of the present invention is as follows

First, get the raw materials ready

1st, Radix Rehmanniae：Crude drug is taken, impurity is removed, is cleaned, slightly moistened, cut sheet, be dried, weed out chip；

2nd, Radix Scrophulariae：Net impurity is picked, except removing LU, is cleaned and is run through, cut into slices, dried；

3rd, Rhizoma Chuanxiong：Impurity is picked, separates large and small, be soaked in water, solarization is dried in the air, cut into slices after moistening, be dried；

4th, Radix Paeoniae Rubra：Crude drug is taken, impurity is removed, size stepping is cleaned, run through, shave, is dried, and weeds out chip；

5th, Flos Carthami：Net impurity is picked, stem and leaf, base of a fruit head is removed, is dried；

6th, Rhizoma Sparganii：Net impurity is picked, is soaked in water, pulled out and run through, cut into slices, dried；

7th, Semen Persicae：Duricrust impurity is removed, is put in boiling water pot and is boiled to crust microcreping, pulled out, in immersion cold water, kind of a skin is removed in stranding, is dried, Winnow with a dustpan net；

8th, Hirudo：Clean, vexed soft, cutting is dried；

9th, Herba Artemisiae Scopariae：Sieve, pick impurity, remove undesirable root, pulverize, after weeding out net spare；

10th, Fructus Gardeniae：Grey bits are weeded out, impurity is picked, is pulverized and is sieved or cut off two ends；

11st, Cortex Magnoliae Officinalis：It is soaked in water and pulls out, rough bark is scraped off after running through, clean, shredding is dried；

12nd, Flos Lonicerae：Silt is weeded out, net impurity is picked；

13rd, the Rhizoma Anemarrhenae：Net impurity is picked, is hit with water and is washed, pulled out, softened, section is dried；

14th, Cortex Moutan：Impurity is picked, core is removed, is cleaned, run through, cut into slices, dried；

15th, Herba Leonuri：Impurity is picked, is cleaned, run through, cutting is dried；

16th, Radix Arnebiae (Radix Lithospermi)：Clean, run through, cut into slices, dry；

17th, Radix Puerariae：Impurity is picked, is cleaned, be soaked in water, pulled out, run through, in time section, dries；

18th, Ramulus Mori：Impurity is picked, is cleaned, be soaked in water, after running through, cutting is dried；

19th, Radix Polygoni Multiflori：Impurity is picked, is cleaned, pulled out with blister to eighty per cant thoroughly, moisten uniform to inside and outside humidity, cut into slices or the side of being cut into Block, dries；

20th, Pseudobulbus Bletillae (Rhizoma Bletillae)：Impurity is picked, is soaked in water, pulled out, dry in the air suitable to humidity, section is dried；

21st, Colla Corii Asini：Smash use to pieces.

2nd, prepare

1st, by the Radix Rehmanniae of the weight, Radix Scrophulariae, Rhizoma Chuanxiong, Radix Paeoniae Rubra, Flos Carthami, Rhizoma Sparganii, Semen Persicae, Hirudo, Herba Artemisiae Scopariae, Fructus Gardeniae, Cortex Magnoliae Officinalis, Flos Lonicerae, the Rhizoma Anemarrhenae, Cortex Moutan, Herba Leonuri, Radix Arnebiae (Radix Lithospermi), Radix Puerariae, Ramulus Mori, Radix Polygoni Multiflori, Pseudobulbus Bletillae (Rhizoma Bletillae), Colla Corii Asini are put in decocting container, add water 8 Measure again, after soaking 100 minutes, fry by intense fire to boil and rise, then with being cooked by slow fire 20 minutes, first time decoction liquor is filtered to obtain, by first Secondary decoction liquor is poured in container；

2nd, the medicinal residues of filtration are added water 6 times and is measured, boiled by intense fire, then with being cooked by slow fire 20 minutes, filter to obtain second decoction liquor；

3rd, will decoction liquor mixing and stirring twice, be divided into 3 doses and take.

Radix Rehmanniae has removing heat from blood, yin nourishing in prescription, and the function of promoting the production of body fluid is monarch drug；Fructus Gardeniae has heat clearing away, pathogenic fire purging, the function of removing heat from blood； Cortex Moutan has heat clearing away, removing heat from blood, and blood, the function of repercussive, and the two is ministerial drug, and three taste medicines play removing heat from blood jointly, and yin nourishing is promoted the production of body fluid, clearly Heat, removing heat from blood, and blood, the effect of repercussive, treatment primary thrombocytosiss effect comprehensively, and with removing heat from blood, yin nourishing, is promoted the production of body fluid, and Can effect a permanent cure based on blood, Herba Leonuri has a promoting blood circulation, blood stasis dispelling, regulating menstruation, the function of the water that disappears is adjuvant drug, Radix Polygoni Multiflori has a tonifying liver, kidney tonifying, blood-nourishing, To make medicine, all medicines are to take stopgap measures to the function of wind-dispelling with being left.

Medicine of the present invention has removing heat from blood, and yin nourishing is promoted the production of body fluid, heat clearing away, removing heat from blood, and blood, tonifying liver, kidney tonifying, and the function of blood-nourishing is used for Treatment primary thrombocytosiss, short treating period, instant effect, non-relapse after healing.

The beneficial effect of medicine of the present invention is expanded on further below by way of test example, these test examples are including this The animal toxicity test report of bright medicine and clinical observation on the therapeutic effect data.

The animal toxicity test report of [test example 1] medicine of the present invention：

Rabbit 30 is taken, male and female dual-purpose, 2.0-2.5kg of body weight is divided to two groups, and 15 per group, one of which is overdose test Group, another group is normal amount test group.Super quantity group is 20ml/kg, and normal amount is 10ml/kg, and administering mode is given for administration by gavage Medicine, twice daily, serve on 7 days, the reaction of observation administration daily, as a result shows that two groups of rabbit activities, diet are normal, and medicine is without bad Toxic and side effects.

The clinical observation on the therapeutic effect of [test example 2] medicine of the present invention

1st, physical data

Accept primary thrombocytosiss out-patient totally 31 for medical treatment.

2nd, diagnostic criteria

Primary thrombocytosiss' course of disease is slow, and the main clinical manifestation of primary disease is bleeding and thrombosiss, platelet count Significantly increase, it is different from other myeloproliferative diseases, heating, hyperhidrosis, lose weight etc. it is very rare.

3rd, Therapeutic Method

From above-mentioned medicament, take to patient, each take 1 dose, early daily, evening respectively takes 1 time, be within 15 days a course for the treatment of, continuously Take 3 courses for the treatment of.

4th, efficacy assessment standard

It is effective：Primary thrombocytosiss' symptom disappears, and recovers normal, recovery from illness；

Take a turn for the better：Primary thrombocytosiss' symptom is clearly better, and platelet count is reduced, and body constitution is progressively recovered；

It is invalid：Improvement standard person is not reached.

5th, therapeutic outcome（See the table below）

It is as a result effective 25, effective with Drug therapy primary thrombocytosiss patient of the present invention 31 in above-mentioned treatment Rate is 80.6%, is taken a turn for the better 4, and improvement rate is 12.9%, and invalid 2, total effective rate is 93.5%.

Claims

1. a kind of medicine for treating primary thrombocytosiss, it is characterised in that：It is by the raw material in following weight range Medicine is made：

2. medicine according to claim 1, wherein the consumption of each crude drug is：

3. the preparation method of medicine according to claim 1 or claim 2, it comprises the following steps：

（One）Get the raw materials ready

（1）Radix Rehmanniae：Crude drug is taken, impurity is removed, is cleaned, slightly moistened, cut sheet, be dried, weed out chip；

（2）Radix Scrophulariae：Net impurity is picked, except removing LU, is cleaned and is run through, cut into slices, dried；

（3）Rhizoma Chuanxiong：Impurity is picked, separates large and small, be soaked in water, solarization is dried in the air, cut into slices after moistening, be dried；

（4）Radix Paeoniae Rubra：Crude drug is taken, impurity is removed, size stepping is cleaned, run through, shave, is dried, and weeds out chip；

（5）Flos Carthami：Net impurity is picked, stem and leaf, base of a fruit head is removed, is dried；

（6）Rhizoma Sparganii：Net impurity is picked, is soaked in water, pulled out and run through, cut into slices, dried；

（7）Semen Persicae：Duricrust impurity is removed, is put in boiling water pot and is boiled to crust microcreping, pulled out, in immersion cold water, kind of a skin is removed in stranding, is shone It is dry, winnow with a dustpan net；

（8）Hirudo：Clean, vexed soft, cutting is dried；

（9）Herba Artemisiae Scopariae：Sieve, pick impurity, remove undesirable root, pulverize, after weeding out net spare；

（10）Fructus Gardeniae：Grey bits are weeded out, impurity is picked, is pulverized and is sieved or cut off two ends；

（11）Cortex Magnoliae Officinalis：It is soaked in water and pulls out, rough bark is scraped off after running through, clean, shredding is dried；

（12）Flos Lonicerae：Silt is weeded out, net impurity is picked；

（13）The Rhizoma Anemarrhenae：Net impurity is picked, is hit with water and is washed, pulled out, softened, section is dried；

（14）Cortex Moutan：Impurity is picked, core is removed, is cleaned, run through, cut into slices, dried；

（15）Herba Leonuri：Impurity is picked, is cleaned, run through, cutting is dried；

（16）Radix Arnebiae (Radix Lithospermi)：Clean, run through, cut into slices, dry；

（17）Radix Puerariae：Impurity is picked, is cleaned, be soaked in water, pulled out, run through, in time section, dries；

（18）Ramulus Mori：Impurity is picked, is cleaned, be soaked in water, after running through, cutting is dried；

（19）Radix Polygoni Multiflori：Impurity is picked, is cleaned, pulled out with blister to eighty per cant thoroughly, moisten uniform to inside and outside humidity, cut into slices or be cut into Square, dries；

（20）Pseudobulbus Bletillae (Rhizoma Bletillae)：Impurity is picked, is soaked in water, pulled out, dry in the air suitable to humidity, section is dried；

（21）Colla Corii Asini：Smash use to pieces；

（Two）Prepare

（1）By the Radix Rehmanniae of the weight, Radix Scrophulariae, Rhizoma Chuanxiong, Radix Paeoniae Rubra, Flos Carthami, Rhizoma Sparganii, Semen Persicae, Hirudo, Herba Artemisiae Scopariae, Fructus Gardeniae, thickness Piao, Flos Lonicerae, the Rhizoma Anemarrhenae, Cortex Moutan, Herba Leonuri, Radix Arnebiae (Radix Lithospermi), Radix Puerariae, Ramulus Mori, Radix Polygoni Multiflori, Pseudobulbus Bletillae (Rhizoma Bletillae), Colla Corii Asini are put in decocting container, plus After 8 times of water amount, immersion 100 minutes, fry by intense fire to boil and rise, then with being cooked by slow fire 20 minutes, filter to obtain first time decoction liquor, by the One time decoction liquor is poured in container；

（2）The medicinal residues of filtration are added water 6 times and is measured, boiled by intense fire, then with being cooked by slow fire 20 minutes, filter to obtain second decoction liquor；

（3）Decoction liquor mixing and stirring twice is incited somebody to action, is divided into 3 doses and is taken.