CN101069683A - Meclofenoxate hydrochloride medicine use - Google Patents
Meclofenoxate hydrochloride medicine use Download PDFInfo
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- CN101069683A CN101069683A CN 200710052352 CN200710052352A CN101069683A CN 101069683 A CN101069683 A CN 101069683A CN 200710052352 CN200710052352 CN 200710052352 CN 200710052352 A CN200710052352 A CN 200710052352A CN 101069683 A CN101069683 A CN 101069683A
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- meclofenoxate hydrochloride
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- meclofenoxate
- injection
- femur head
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- XZTYGFHCIAKPGJ-UHFFFAOYSA-N Meclofenoxate Chemical compound CN(C)CCOC(=O)COC1=CC=C(Cl)C=C1 XZTYGFHCIAKPGJ-UHFFFAOYSA-N 0.000 title claims abstract description 38
- 229960001637 meclofenoxate hydrochloride Drugs 0.000 title claims abstract description 27
- 239000003814 drug Substances 0.000 title claims abstract description 11
- 238000002360 preparation method Methods 0.000 claims abstract description 5
- 208000007875 Femur Head Necrosis Diseases 0.000 claims description 19
- 238000002347 injection Methods 0.000 abstract description 10
- 239000007924 injection Substances 0.000 abstract description 10
- 238000000034 method Methods 0.000 abstract description 6
- 206010028851 Necrosis Diseases 0.000 abstract description 2
- 239000002775 capsule Substances 0.000 abstract description 2
- 230000017074 necrotic cell death Effects 0.000 abstract description 2
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- 241001465754 Metazoa Species 0.000 description 12
- 210000000988 bone and bone Anatomy 0.000 description 9
- 241001484259 Lacuna Species 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 210000001789 adipocyte Anatomy 0.000 description 6
- 238000010171 animal model Methods 0.000 description 6
- 230000037182 bone density Effects 0.000 description 6
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 206010031264 Osteonecrosis Diseases 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- LRJOMUJRLNCICJ-JZYPGELDSA-N Prednisolone acetate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O LRJOMUJRLNCICJ-JZYPGELDSA-N 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 210000004394 hip joint Anatomy 0.000 description 3
- 210000004409 osteocyte Anatomy 0.000 description 3
- 229960002800 prednisolone acetate Drugs 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 208000006820 Arthralgia Diseases 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 206010020880 Hypertrophy Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- 230000002146 bilateral effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000000845 cartilage Anatomy 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 210000002745 epiphysis Anatomy 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 150000002960 penicillins Chemical class 0.000 description 2
- 208000037920 primary disease Diseases 0.000 description 2
- 108010048734 sclerotin Proteins 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- SODPIMGUZLOIPE-UHFFFAOYSA-N (4-chlorophenoxy)acetic acid Chemical compound OC(=O)COC1=CC=C(Cl)C=C1 SODPIMGUZLOIPE-UHFFFAOYSA-N 0.000 description 1
- -1 2-(dimethylamino) ethyl Chemical group 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 206010002660 Anoxia Diseases 0.000 description 1
- 241000976983 Anoxia Species 0.000 description 1
- 208000008967 Enuresis Diseases 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 241000446313 Lamella Species 0.000 description 1
- 206010027336 Menstruation delayed Diseases 0.000 description 1
- 206010053156 Musculoskeletal discomfort Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 208000008765 Sciatica Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000010513 Stupor Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000003470 adrenal cortex hormone Substances 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 230000007953 anoxia Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000008407 joint function Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004705 lumbosacral region Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229960003442 meclofenoxate Drugs 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 229940056360 penicillin g Drugs 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 208000037922 refractory disease Diseases 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 238000012109 statistical procedure Methods 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 201000004595 synovitis Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000004804 winding Methods 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention relates to a new application of meclofenoxate hydrochloride for preparing medicine for curing necrosis of femoral head with good therapeutic effect. The invented medicine can be made into injection preparation, also can be made into oral preparation, for example meclofenoxate hydrochloride capsule, etc. Said invention also provides its application method.
Description
Technical field
The present invention relates to the new medical use of meclofenoxate hydrochloride, i.e. the application of meclofenoxate hydrochloride in the medicine of preparation treatment femur head necrosis belongs to medical technical field.
Background technology
Femur head necrosis is that composition alive (osteocyte, myeloid element and the adipose cell) death with bone is the main pathological process that changes.Femur head necrosis is world's pertinacious disease, because its cause of disease complexity, and the treatment difficulty, it is very high to treat untimely disability rate, seriously jeopardizes patient's live and work, thereby is called " not dead cancer " by people, and as seen its harm has much.Osteonecrosis is the most common with femur head necrosis.It is reported that the annual new cases of China's femur head necrosis are between 15～200,000, accumulation needs the case of treatment between 5,000,000～7,500,000.State's Ministry of Public Health such as Japan, the U.S. are classified this disease as unsolved refractory disease, drop into huge fund research, but it are to be solved to still have many difficult problems to have.The femur head necrosis onset is slow, and the course of disease is longer, at a very long time patient non-evident sympton.Modal clinical symptoms is hip discomfort or pain, and pain is obvious behind tired back or the walking for a long time, and the back of having a rest is alleviated.In the femur head necrosis pathogenic process, the lumbosacral region or the gonalgia often appear, easily the mistaken diagnosis lumbar intervertebral disc deviate from, spinal canal stenosis, sciatica, rheumatic arthritis, synovitis etc.The weight that the outstanding feature of primary disease is a subjective symptoms is not directly proportional with the femur head necrosis destructiveness, and patient will pay special attention to.Along with walking lamely and pain increases the weight of, hip joint function is limited gradually, can make late period hip joint stiff and disable.In recent years, along with adrenocortical hormone extensive use clinically, the femur head necrosis that causes thus is much accounted of day by day.Because of primary disease mainly involves young and middle-aged people, and bilateral is seen serious harm patient's labour force and life quality more.About 80% untreated femur head necrosis patient can generation collapse of the femoral head in 1～4 year after morbidity.In a single day femoral head subsides, then hip joint severe osteoarthritis takes place inevitably and make patient's arthralgia, joint motion is limited and the pedestrian worker's joint replacement of having to.But present level, long-term (more than 15～20 years) good curative effect of young and middle-aged artificial joint replacement are still certainly difficult.Therefore, how reducing the incidence rate of this type of osteonecrosis, can obtain early diagnosis and effectively treatment in case necrose, make the patient keep self femoral head as far as possible, avoid or postpone the prosthetic replacement, is the problem that presses for solution at present.
Meclofenoxate hydrochloride, its chemical name is: 2-(dimethylamino) ethyl parachlorophen-oxyacetic acid ester hydrochloride, this product can promote the oxidoreduction metabolism of brain cell, increases the utilization to saccharide, maincenter is suppressed the patient excitation; Traumatic stupor, alcoholism, anoxia neonatorum disease, child's enuresis there is certain curative effect [referring to the meclofenoxate hydrochloride injection description of (sino-america joint-venture) SHANXI POWERDONE PHARMACEUTICAL.,LTD and Hunan WZT Pharmaceutical Co., Ltd].But do not see the report that has meclofenoxate hydrochloride femur head necrosis to be had medical function.
Summary of the invention
Problem to be solved by this invention provides the new medical use of meclofenoxate hydrochloride, and the medicine for preparing with meclofenoxate hydrochloride has curative effect preferably to femur head necrosis.
Technical scheme provided by the invention is: the application of meclofenoxate hydrochloride in the medicine of the femur head necrosis of preparation treatment treatment.
The present invention stays with meclofenoxate hydrochloride treatment femur head necrosis has curative effect preferably.Medicine of the present invention (as meclofenoxate hydrochloride injection) can give by intramuscular injection, intravenous injection or intravenous drip etc., also can adopt oral formulations (example hydrochloric acid meclofenoxate capsule etc.) orally give.Its consumption generally can give according to the routine dose of meclofenoxate hydrochloride injection in the prior art.The present invention recommends usage and dosage: intravenous injection or intravenous drip, every day 2-3 time, each 0.06～0.25g; Intramuscular injection, a 0.06-0.25, per 2 hours are once.
The specific embodiment
The present invention further specifies effect of the present invention by following experimental data.
1. experiment material:
1.1 animal
Laboratory animal: the Japan large ear rabbit of growing up, 2.1～3.0kg is provided by institute for drug control, Hunan Province Experimental Animal Center, quality certification SYXK (Hunan) 2003-0006 number.
1.2 medicine and reagent
Meclofenoxate hydrochloride injection: (sino-america joint-venture) SHANXI POWERDONE PHARMACEUTICAL.,LTD, specification: 0.25g/ bottle; Lot number: 030901; Face with preceding stand-by with the water for injection dilution.
Predniso lone acetate: Hubei Pharmaceutic Works produces, specification: 125mg/5ml lot number: 20040918.
Benzylpenicillin sodium for injection Xinan Pharmaceutical Co., Ltd., specification: 800,000 U, lot number: 20040309 face with preceding stand-by with the water for injection dilution.
2. experimental technique and data
2.1 animal grouping
Get 24 of Japan large ear rabbits, respectively get 8 at random and be divided into normal control group, model group and meclofenoxate hydrochloride group.
Normal control group: intragluteal injection normal saline;
Model group: every 2 intragluteal injection 6mg predniso lone acetate/kg and 80,000 U penicillins/only weekly, 12 weeks;
Meclofenoxate hydrochloride group: every 2 intragluteal injection 6mg predniso lone acetate/kg and 80,000 U penicillins/only, inject 60mg meclofenoxate hydrochloride injection/kg, 12 weeks simultaneously every day weekly;
2.2 test item and method:
2.2.1 lipids detection:
3 treated animals are in blood sampling on an empty stomach.Get 3ml blood, after waiting to separate out serum, adopt the automatic biochemistry analyzer enzyme-linked method to survey serum total cholesterol and triglyceride.
2.2.2 histopathological examination:
Each treated animal takes out bilateral femoral head in the back execution of 12 weeks, fixes with 10% formalin buffer, and 5% salpeter solution decalcification, specimen is vertically cut in the flowing water flushing after the decalcification, through step concentration ethanol solution dehydrates, does specimens paraffin embedding slices, HE dyeing.When observing the skeleton section, optional 10 high power fields of femoral head cartilage inferior segment, 50 lacunas of every visual field counting are counted clearancen bone lacuna number respectively, obtain meansigma methods.
2.2.3 the femoral head bone density detects:
Use the light quantum bone density meter and measure the capital bone density of 3 treated animals.
2.3 the processing of experimental data:
Adopt the t method of inspection that compares between mean to carry out statistical procedures.
3. result
3.1 blood fat:
Table 1 meclofenoxate hydrochloride is to the influence of laboratory animal serum cholesterol and triglyceride (X ± S)
| Group | n | Serum total cholesterol | Triglyceride |
| The normal control group | 8 | 1.52±0.41 | 0.90±0.31 |
| Model group | 8 | 4.60±0.88 ** | 3.84±0.82 ** |
| The meclofenoxate hydrochloride group | 8 | 2.26±0.42 △△ | 1.42±0.29 △△ |
Annotate:
*For comparing P＜0.01 with normal group;
△ △For comparing P＜0.01 with model group.
Table 1 shows that the serum cholesterol of model group and triglyceride all are significantly higher than normal control group and meclofenoxate hydrochloride group; Though the normal matched group of meclofenoxate hydrochloride group raises not statistically significant (P＞0.05) to some extent.
3.2 histopathology result:
Table 2 meclofenoxate hydrochloride is to the influence of laboratory animal pulp cavity fat cell hypertrophy hyperplasia degree and osteonecrosis
| Group | n | The adipose cell proliferation degree | Medullary cavity osteonecrosis kitchen range |
| The normal control group | 8 | A little | Do not have |
| Model group | 8 | Obviously | Many |
| The meclofenoxate hydrochloride group | 8 | A little | Few |
Table 3 meclofenoxate hydrochloride is to the influence of laboratory animal femoral head bone lacuna number (X ± S)
| Group | n | The bone lacuna number |
| The normal control group | 8 | 12.7±3.38 |
| Model group | 8 | 33.5±7.83 ** |
| The meclofenoxate hydrochloride group | 8 | 21.9±4.95 △△ |
Annotate:
*For comparing P＜0.01 with normal group;
△ △For comparing P＜0.01 with model group.
Normal control group and the gross anatomy of meclofenoxate hydrochloride treated animal femoral head show no obvious abnormalities; To a certain degree sclerotin evacuation all appears in model group and meclofenoxate hydrochloride group, and model group is particularly evident.The bone lacuna number increases under the model group light microscopic, and the adipose cell number increases, and the interior blood vessel of marrow that closes on subcartilaginous osseous lamella is very thin, and the sinusoid blood vessel is thick in the epiphysis portion pulp cavity, coincide to be netted, and district's trunk is arranged along the line of force bearing a heavy burden.Transmission electron microscope partial femoral head osteocyte volume-diminished, karyopycnosis, more osteocyte necrolysis fragmentates; Medullary cell in the pulp cavity of non-necrotic area is replaced by adipose cell substantially; Chondrocyte is arranged in order under the normal control group light microscopic, and the shallow district of cartilage following table sclerotin is domes, and transitional areas and the stringer of central area bone trabecula are arranged towards articular surface.The visible small amount of bone lacuna of meclofenoxate hydrochloride group light microscopic inferior segment, but the bone lacuna number is than model group few (P＜0.01), and the bone marrow fat cell hypertrophy increases not obvious, visible point-like necrosis region in the pulp cavity, the sinusoid blood vessel is oppressed to some extent in the epiphysis portion pulp cavity, compares but with model group obviously to alleviate.
3.3 histopathology result:
Table 4 meclofenoxate hydrochloride is to the influence of laboratory animal femoral head bone density (X ± S)
| Group | n | Femoral head bone density (g/cm 3) |
| The normal control group | 8 | 0.878±0.148 |
| Model group | 8 | 0.839±0.186 ** |
| The meclofenoxate hydrochloride group | 8 | 0.868±0.131 △△ |
Annotate:
*For comparing P＜0.01 with normal group;
△ △For comparing P＜0.01 with model group.
Experiment shows that meclofenoxate hydrochloride group femoral head bone density is apparently higher than model group (P＜0.01), and is near with the normal control winding.Illustrate that the present invention adopts the meclofenoxate hydrochloride treatment that certain positive role is played in the progress that prevents femur head necrosis, the reparation of promotion bone.
4. conclusion
The present invention shows that by the experiment to the effect of laboratory animal femur head necrosis meclofenoxate hydrochloride of the present invention is used for the treatment of femur head necrosis and has effect preferably.Disclose the medicine that meclofenoxate hydrochloride of the present invention can be used as the treatment femur head necrosis.
Claims (1)
1. the new medical use of meclofenoxate hydrochloride is characterized in that: the application of meclofenoxate hydrochloride in the medicine of preparation treatment femur head necrosis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2007100523521A CN100515417C (en) | 2007-06-01 | 2007-06-01 | Applicaiton of meclofenoxate hydrochloride in preparing medicine for treating femoral head necrosis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2007100523521A CN100515417C (en) | 2007-06-01 | 2007-06-01 | Applicaiton of meclofenoxate hydrochloride in preparing medicine for treating femoral head necrosis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101069683A true CN101069683A (en) | 2007-11-14 |
| CN100515417C CN100515417C (en) | 2009-07-22 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2007100523521A Active CN100515417C (en) | 2007-06-01 | 2007-06-01 | Applicaiton of meclofenoxate hydrochloride in preparing medicine for treating femoral head necrosis |
Country Status (1)
| Country | Link |
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| CN (1) | CN100515417C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113332271A (en) * | 2021-03-31 | 2021-09-03 | 中山大学孙逸仙纪念医院 | Application of meclofenoxate hydrochloride in preparation of medicine for preventing or treating Parkinson's disease |
-
2007
- 2007-06-01 CN CNB2007100523521A patent/CN100515417C/en active Active
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113332271A (en) * | 2021-03-31 | 2021-09-03 | 中山大学孙逸仙纪念医院 | Application of meclofenoxate hydrochloride in preparation of medicine for preventing or treating Parkinson's disease |
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| Publication number | Publication date |
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| CN100515417C (en) | 2009-07-22 |
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Denomination of invention: Applicaiton of meclofenoxate hydrochloride in preparing medicine for treating femoral head necrosis Effective date of registration: 20110201 Granted publication date: 20090722 Pledgee: Bank of Communications Ltd Wuhan East Lake New Technology Development Zone sub branch Pledgor: Tongyuan Pharmaceutical Ind Co., Ltd., Wuhan Registration number: 2011990000041 |
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Effective date of registration: 20180827 Address after: 519015, 2 floor, Heping industrial center, No. 209 Shihua Road, Zhuhai, Guangdong. Patentee after: Zhuhai morning Ann Pharmaceutical Co., Ltd. Address before: 430071 No. 100 purple sand road, Wuchang District, Wuhan, Hubei. Patentee before: Tongyuan Pharmaceutical Ind Co., Ltd., Wuhan |
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