CN106138374A

CN106138374A - The application in terms of preparation treatment disease of thymus gland medicine of gynecological's prescriptions worth thousand gold compositions combined with antibiotic

Info

Publication number: CN106138374A
Application number: CN201610663186.8A
Authority: CN
Inventors: 李伏君; 龚云; 李维; 刘逆夫; 张鹏
Original assignee: Zhuzhou Qianjin Pharmaceutical Co Ltd
Current assignee: Zhuzhou Qianjin Pharmaceutical Co Ltd
Priority date: 2016-08-12
Filing date: 2016-08-12
Publication date: 2016-11-23

Abstract

The invention discloses the application in terms of preparation treatment disease of thymus gland medicine of a kind of gynecological prescriptions worth thousand gold compositions combined with antibiotic, the especially application in terms of preparation treatment improves thymus hyperemia, edema and hypertrophy medicine, described antibiotic is azithromycin.The active component of described gynecological prescriptions worth thousand gold compositions is made up of Radix Flemingiae Philippinensis, Herba Andrographis, Radix Rosae Laevigatae, Caulis Mahoniae, Fructus Zanthoxyli Dissiti, Caulis Spatholobi, Radix Angelicae Sinensis and Radix Codonopsis.Chinese medicine composition of the present invention associating azithromycin has good application effect at aspects such as improving thymus hyperemia, edema, hypertrophy.

Description

Gynecological's prescriptions worth thousand gold compositions combined with antibiotic is in terms of preparation treatment disease of thymus gland medicine Application

Technical field

The present invention relates to pharmaceutical technology field, exist more particularly, to a kind of gynecological prescriptions worth thousand gold compositions combined with antibiotic Application in terms of preparation treatment disease of thymus gland medicine.

Technical background

Thymus (thymus) thymus is positioned at thoracic cavity anterior mediastinum, for the important lymphatic organ of body.Its function is tight with immunity Relevant, it is T cell differentiation, growth, ripe place, it can also be secreted thymosin and hormonal substance, have endocrine machine The organ of energy.Thymus is called " the life-span clock " of people, and research in recent years shows closely related with the life-span length of people.

Thymus is the vitals of human immunity particularly cellular immunization, therefore when thymus has pathological changes, will be to immunity of organism merit Can bring and have a strong impact on, make immunity of organism from steady dysfunction the autoimmune disease that occurs together.Disease of thymus gland can be by its size Classification, divide Primary congenital thymic dysplasia less than normal thymus, be secondary to adrenal cortex function hyperfunction, pregnant, Lactication, malnutrition, steroid and cytotoxic drug therapy and lonizing radiation irradiation etc.；Thymoma, breast is had more than normal thymus After other tumors of gland, metastatic tumor, thymic cyst, wound hemorrhage etc..

A lot of diseases can cause thymic hyperplasia, such as: infection seriously or repeatedly, burn, sarcoidosis, simple regeneration of erythrocytes Aplastic anemia and the whole body endocrinopathy (including: adrenal gland, pancreas, ovary, kidney etc.) of some complexity.

Azithromycin is applicable to the infection caused by sensitive bacterial, including the lower respiratory infection such as bronchitis, pneumonia, skin Skin and soft tissue infection, acute otitis media, the upper respiratory tract infection such as sinusitis, pharyngitis, tonsillitis.The most also have and see and be used in Treatment pelvic inflammatory disease.

Have no that Chinese medicine composition and azithromycin are united and applied in the correlation technique of preparation treatment disease of thymus gland medicine at present Report.

Summary of the invention

The technical problem to be solved in the present invention is to fill up the application technology deficiency of existing FUKE QIANJIN PIAN associating azithromycin, The application in terms of the medicine of preparation treatment disease of thymus gland of a kind of gynecological prescriptions worth thousand gold compositions combined with antibiotic is provided.

The purpose of the present invention is achieved by the following technical programs:

There is provided the application in terms of the medicine of preparation treatment disease of thymus gland of gynecological's prescriptions worth thousand gold compositions combined with antibiotic, especially It is to be applied to the application in terms of preparation treatment improves thymus hyperemia, edema and/or hypertrophy medicine；Described antibiotic is Archie Mycin；The active component of described gynecological prescriptions worth thousand gold compositions is by Radix Flemingiae Philippinensis, Herba Andrographis, Radix Rosae Laevigatae, Caulis Mahoniae, Fructus Zanthoxyli Dissiti, Sanguis Gallus domesticus Rattan, Radix Angelicae Sinensis and Radix Codonopsis composition.

The application in terms of preparation reduces thymus organ index medicine of gynecological's prescriptions worth thousand gold compositions combined with antibiotic is provided,

Preferably, in described Chinese medicine composition, the incorporation of Radix Angelicae Sinensis, Radix Codonopsis, Herba Andrographis and Fructus Zanthoxyli Dissiti is respectively medical material gross weight The 9% of amount；The incorporation of Radix Rosae Laevigatae, Caulis Spatholobi, Caulis Mahoniae and Radix Flemingiae Philippinensis is respectively the 16% of medical material gross weight.

Preferably, in described Chinese medicine composition, the incorporation of Herba Andrographis and Fructus Zanthoxyli Dissiti is respectively the 9% of medical material gross weight；Gold The incorporation of cherry root, Caulis Mahoniae and Radix Flemingiae Philippinensis is respectively the 16% of medical material gross weight.

The preparation method of described Chinese medicine composition can refer to Zhuzhou Qianjin Pharmacy Co., Ltd's FUKE QIANJIN PIAN or glue The preparation method of capsule.

The invention has the beneficial effects as follows:

The invention provides gynecological's prescriptions worth thousand gold compositions combined with antibiotic answering in terms of preparation treatment disease of thymus gland medicine With, azithromycin is applicable to the infection caused by sensitive bacterial, including the lower respiratory infection such as bronchitis, pneumonia, skin and Soft tissue infection, acute otitis media, the upper respiratory tract infection such as sinusitis, pharyngitis, tonsillitis.The present invention by its with by very heavy Pull out, Herba Andrographis, Radix Rosae Laevigatae, Caulis Mahoniae, Fructus Zanthoxyli Dissiti, Caulis Spatholobi, Radix Angelicae Sinensis and Radix Codonopsis eight taste medicine composition Chinese medicine composition combine should With, in terms for the treatment of disease of thymus gland especially improves thymus hyperemia, edema and hypertrophy, there is good application effect, and Prove that described Chinese medicine composition and azithromycin play synergism by a large amount of zooperies, become to improving thymus organ index Having definite influence to normal aspect, the frontier application for Chinese medicine composition and azithromycin both provides strong skill Art is supported.

Accompanying drawing explanation

Uterus organ coefficient situation of change before and after the treatment of Fig. 1 AZM, AZMQR, AZMDG, AZMFF group.

Thymus organ coefficient situation of change before and after the treatment of Fig. 2 AZM, AZMQR, AZMDG, AZMFF group.

Detailed description of the invention

The present invention is further illustrated below in conjunction with specific embodiment.Following embodiment being merely cited for property explanation, it is impossible to reason Solve as limitation of the present invention.Unless stated otherwise, the raw material used in following embodiment obtains for conventional commercial or commercial sources The raw material obtained, unless stated otherwise, the method and apparatus used in following embodiment is method commonly used in the art and sets Standby.

Embodiment 1

1. experimental strain: staphylococcus aureus (ATCC25923), escherichia coli (ATCC25922) is bought in China Country's strain library.Strain subject lyophilized powder is uniformly laid on aseptic M-H (A) planar surface with after aseptic M-H (B) culture medium suspendible, 35 DEG C of overnight incubation are brought back to life, and 18h rear plate superficial growth goes out lawn, chooses the single cenobium wherein grown fine, again smears In M-H (A) inclined-plane, under the same terms, hatch 18h, seal, stored refrigerated under the conditions of 4 DEG C；Test takes inclined-plane bacterium and smears the previous day In M-H (A) flat board, 35 DEG C of overnight incubation, can use.All operations all completes at superclean bench.

2. bacterium solution preparation method

Method one: (prepared by high concentration bacterium solution)

Choose 3-4 single bacterium colony in M-H (B) culture medium of 40 milliliters.Tested bacterium Zengjing Granule overnight 16 hours (37 DEG C, Shaking bath shakes 16 hours), take out original bacteria liquid all-wave length multi-functional reading view next day and survey OD value (the bacterial growth period of saturation)； Take 20mL, be sub-packed in centrifuge tube, often pipe 2mL, centrifugal 10000-15000rpm/min, 10 minutes, abandons or adopts among supernatant M-H (B), after mixing with 2mL normal saline, then is centrifuged 15000rpm/min, 10 minutes, abandons or adopts the normal saline in supernatant, Collect bacterial cell thalline 2mL.Gold-coloured staphylococci and the escherichia coli same procedure cultivated i.e. are obtained by 1:1 mixing 4mL mixed bacteria liquid.It is 100 bacterial concentrations by this bacterium solution, carries out 10 times of dilutions with normal saline, be diluted to 0.1 × 100,0.01 × 100, standby (totally 3 dosage).

Method two: (prepared by low concentration bacterium solution)

Choose single bacterium colony (including gold-coloured staphylococci and escherichia coli) in the normal saline of 2 milliliters, to prepare respectively Become 0.5 Maxwell concentration (about 1 × 108CFU mL^-1) bacterial suspension, by gold-coloured staphylococci and escherichia coli suspension Mixing, i.e. obtains mixed bacteria liquid 4mL.This bacterium solution is set to 10A bacterial concentration, carries out two-fold dilution with normal saline, dilute Release to 0.5 × 10^A, 0.25 × 10^A, standby (totally 3 dosage).

3. medicine and reagent: M-H (A) culture medium (OXOID company, product batch number: CM0337A)；M-H (B) culture medium (OXOID company, product batch number: CM0405B)；Urethane solution (20%)；Normal saline (Cologne, the Sichuan limited public affairs of medicinal liquid share Department, product batch number: M12012004)；Other reagent and consumptive material are bought by Chengdu Ya Rong biochemical equipment business department and are provided.

4. instrument: electro-heating standing-temperature cultivator (the permanent Science and Technology Ltd. in Shanghai one, BPH-9162)；Excellent general series ultrapure water machine (Chengdu Ultra Pure Science & Technology Co., Ltd, UpK-1-10T)；Micro sample adding appliance (EppendorfResearch, 10,100,100uL)； Air bath agitator (the connection electronic technology exploitation of east, Harbin City, HZQ-C)；Automatic electric heating pressure steam sterilization boiler (pacify by Shen, Shanghai Medical apparatus and instruments factory, LDZX-40BI)；All-wave length multi-functional reading view (U.S. Thermo)；Bacterial colony counting instrument.

5. prepared by model

Concrete operation method: rat weight labelling, abdominal part routine disinfection, 20% urethane 0.5mL/100g lumbar injection fiber crops Liquor-saturated, extract previously prepared mixed bacteria liquid with 1mL syringe, left hand is held rat-tail and is mentioned rat, grinds off syringe needle with 10mL syringe Point, the cervix uteri crotch bottom vagina carefully enters in the uterine cavity of side, syringe needle in uterine cavity back and forth pull 2 times with mechanicalness Damage endometrial tissue, then injects bacterium solution 0.1mL towards ovary direction, and 0.1mL bacterium solution is injected another by same operating procedure Aconitum carmichaeli Debx. palace, after injection, is inverted rat 5min, in case bacterium solution spills.Rat infection is respectively organized respectively at 24h, 48h observed and recorded Situation, with rat without death, after modeling, difference vagina scraping blade after 24h, 72h, 96h, carries out bacterium colony cultivation, selects colony counting The infection dosage of >=30 ,≤100 is as optimal infection dosage.Using this bacterium amount as the bacterium amount of In vivo infection.Tested rat infection Bacterium amount is:

Table 1

All laboratory animals 24h, 72h and 96h after modeling, anesthesia, routine disinfection abdominal part, stretches into palace with aseptic cotton carrier Mouthful, back and forth after pull 2 times, cotton swab is put in the test tube containing 2mL normal saline, it is thus achieved that containing test article suspension, takes out cotton swab, Fully dipping mixed liquor uniform application in aseptic M-H (A) planar surface with new aseptic cotton carrier again, 35 DEG C of overnight incubation, after 18h Carry out colony counting.240h sacrifices animal, observes uterine infection situation.Each group typical case Mus infects colony counting, result such as following table 2:

Table 2 tested rat infection bacterium amount

All laboratory animals 24h, 72h and 96h after modeling, anesthesia, routine disinfection abdominal part, show with without bacterium colony count results Showing, 3 groups of Mus institute infection dosages meet requirement of experiment.Meanwhile, the visible inflammatory hyperemia directly perceived of uterus etc. seen from after dissection and inflammatory water Swollen.

6. process of the test

(female SPF SD rat, 220g ± 20g, tested by Sichuan Academy of Medical Sciences for model and 150 rats of packet Institute of Botany is buied, laboratory animal production licence number: SCXK (river) 2008-24).16 are served only for blank, raise separately.Its Yu Jun injects mixed bacteria liquid after using modeling method anesthesia.Observe 5, the most daily randomly draw 6 only reach 2 anesthesia of blank group after Gather vaginal secretions for nacterial smear.After 5 days, survival rats is randomly divided into 5 groups, i.e. model, AZM, AZMQR, AZMDG, AZMFF (represents the model group of not treatment respectively, is used alone azithromycin group, azithromycin heat clearing away merging group, azithromycin Lack Radix Angelicae Sinensis merging group, azithromycin the most just merging group).

Model: the not model group for the treatment of；

AZM: azithromycin

Model: the not model group for the treatment of；

The model group of AZM: azithromycin treatment.

AZMQR: azithromycin+Chinese medicine composition is (with Radix Flemingiae Philippinensis, Herba Andrographis, Radix Rosae Laevigatae, Caulis Mahoniae, Fructus Zanthoxyli Dissiti reference strain Formula proportion and the method for continent a thousand pieces of gold Pharmaceutical FUKE QIANJIN PIAN prepare compositions) therapeutic alliance model group.

AZMDG: azithromycin+Chinese medicine composition is (with Radix Flemingiae Philippinensis, Herba Andrographis, Radix Rosae Laevigatae, Caulis Mahoniae, Fructus Zanthoxyli Dissiti, Sanguis Gallus domesticus Rattan, Radix Codonopsis prepare compositions with reference to formula proportion and the method for Zhuzhou a thousand pieces of gold Pharmaceutical FUKE QIANJIN PIAN) therapeutic alliance model group.

AZMFF: azithromycin+Chinese medicine composition is (with Radix Flemingiae Philippinensis, Herba Andrographis, Radix Rosae Laevigatae, Caulis Mahoniae, Fructus Zanthoxyli Dissiti, Sanguis Gallus domesticus Rattan, Radix Angelicae Sinensis, Radix Codonopsis prepare compositions with reference to formula proportion and the method for Zhuzhou a thousand pieces of gold Pharmaceutical FUKE QIANJIN PIAN) therapeutic alliance model Group.

1. study dosage

(1) AZM dosage: the optional study dosage of azithromycin (AZM) is analyzed and determined by the present embodiment, purpose For select one on probation after action intensity is moderate, duration is moderate study dosage, the most clearly with during Chinese medicine drug combination time Cheng Changdu.Prerun 60,30,20,10mg/kg.d tri-days, find that former setting dosage is too high, finally use 10mg/kg.d.

(2) Test Drug Dosages:

The former dosage setting each Chinese medicine composition is as 2.058g/kg.d, but prerun finds, this dosage uses maximum to volume Preparation is thin pulp shape to medicinal liquid, it is impossible to by gavage syringe needle.It is maximum dosage-feeding with adjusting final full side AZMFF dosage 1.66g/kg.d, adjust lack when be grouped into dosage AZMDG be 1.41g/kg.d, heat clearing away group dosage AZMQR be 1.16g/kg.d.

2. administration time

In addition to blank and model, after modeling the 6th day starts to give relative medicine.AZM gives respectively with each Chinese medicine, difference About 2 hours time.All administration groups, at about 8 AZM the most first giving corresponding dosage, start after two hours to give accordingly Chinese medicine normal saline water mixes thing.

3. sample collection

After 1st gives AZM two hours, respectively organize rat systemic vein blood through tail venous collection.From second day beginning each administration Group rat twice blood sampling every day, before giving Archie and give before Chinese medicine each through tail venous collection the most once, gather blood volume about every time 0.3mL, sample time error about 30min.After administration gives AZM two hours on the 2nd, 4,6,8th, after each group anesthesia, sacrifice about 2 ～4 rats, gather cavity of resorption tremulous pulse anticoagulated whole blood, and collect and sacrifice the target organ of rat and (uterus, incubate nest, thymus, spleen simultaneously Dirty).

4. sample presentation test

All time point 0.3mL and last whole blood, divide and take about 0.2mL blood plasma for UPLC-MS detection AZM concentration.Last Anticoagulated whole blood censorship cytometry, lectin from hemolymph.Uterus is cutting in the middle part of body of uterus, takes after 1/2 formalin is fixed for disease Reason censorship.Uterus, incubate nest, thymus, spleen are weighed and calculate organ coefficient.Organ coefficient, also known as dirty body ratio, is laboratory animal The weight of internal organs and the ratio of its body weight.Time normal, each internal organs are more constant with the odds ratio of body weight.After animal contaminated, impaired internal organs Weight can change, therefore organ coefficient changes the most therewith.Organ coefficient increases, and represents internal organs hyperemia, edema or hypertrophy Loose etc.；Organ coefficient reduces, and represents internal organs atrophy and other degenerative changes.

Experimental result is as shown in Fig. 1 and Fig. 2.In Fig. 1 and Fig. 2, be respectively indicated as from left to right AMZ, AMZDG, AZMFF, The index variation situation of AZMQR, Model and normal group normal.Result shows, after laboratory animal modeling, uterus and thymus are equal Congested, edema, organ coefficient compares with normal group and all raises, and after giving different combinational drug therapy, each coefficient all reduces, and becomes To in replying normal level.Therapeutic effect between each treatment group compares, uterus organ coefficient: AZMDG > AZMQR > AZMFF > AZM；Thymus organ coefficient: AZMFF > AZMDG > AZM > AZMQR.Gynecological's prescriptions worth thousand gold compositions associating azithromycin is mainly improving The aspects such as thymus hyperemia, edema, hypertrophy have good application effect.

The test in terms of the auxiliary treatment of thymus relevant disease of the embodiment 2 Chinese medicine composition of the present invention associating azithromycin

Myasthenia gravis (MG) is a kind of handicapped acquired autoimmune disease of neuromuscular transmission.Its Definite pathogeny is the most indefinite, but the research about this disease is the most, and wherein, most study is relevant serious symptom flesh The unable relation with thymus.Research prove, the anti-Achr antibody in serum increase with the deposition on postsynaptic membrane caused by The minimizing of effective Achr number, is this pathogenetic main cause.And thymus is the main place that Achr antibody produces, because of This, the generation of primary disease is general and thymus has close relationship.The present embodiment is based on the early stage influence to thymus organ index Research, it is intended to understand in Chinese medicine composition of the present invention associating myasthenia gravis treatment of diseases and played as auxiliary therapy Effect.

Case selection standard: the diagnostic criteria formulated according to national neuroimmunology conference in 1997: 1. clinical manifestation: live The voluntary muscle alleviated after dynamic postemphasis, rest is unable, and in morning, gently dusk is heavy；2. pharmacology: cholinesterase inhibitors for treating effectively and Curare class medicine is allowed to increase the weight of；3. electrophysiology: Repetitive nerve stimulation shows that compound action potential wave amplitude successively decreases more than 10% He Single fiber EMG show tremble broadening；4. immunology: serum acetylcholine receptor antibodies increases；5. immunopathology: Neuromuscular Meat joint postsynaptic membrane fold reduces, flatten smooth and acetylcholinergic receptor minimizing.In above five, Section 1 and Section 2 symbol Conjunction is the most diagnosable, can take the circumstances into consideration to increase as research for latter three.Refer again to the Syndrome Differentiation of Chinese Medicine of " practical combination of Chinese and Western medicine diagnoses and treatment " Card typing, Pishenqixu syndrome: primary symptom is blepharoptosis, diplopia, myasthenia of limbs, even it is unable to lift neck, hoarseness；Secondary disease is that complexion is few China, shortness of breath and tired spirit, poor appetite, or aversion to cold and cold limbs, soreness of the waist and knees, loose stool；Light red tongue, tongue is the most greasy or thin the most greasy；Moderate pulse or heavy weak Unable person, does not all meet person, get rid of age<5 years old or age>65 years old person, have drug allergy history or high quick body constitution person, merge liver, kidney, The serious disease persons such as cardiovascular system, hemopoietic system, hormonal system；Pregnant and lactant women, patient and family members are involuntary Or can not actively coordinate and participate in other drug researcher.

Ureteral Calculus 31 example altogether, wherein determines that 20 examples are with thymus all hyperemia, edema, thymus organ coefficient and normal group ratio More all raise, described 20 examples are randomly divided into two groups.Two groups in sex, age, the course of disease, disease character, the aspect statistics such as disease of holding concurrently Learn comparing difference not statistically significant (P ＞ 0.05), there is comparability.

Therapeutic Method:

Treatment group: give prednisone sheet 30～50mg and play decoction being taken at a draught morning, subtract 2.5mg after 2 months every other week, until drug withdrawal.Join simultaneously Gastric mucosa protective agent etc. is taken in conjunction.Give FUKE QIANJIN PIAN (capsule) (Zhuzhou Qianjin Pharmacy Co., Ltd produces, ginseng simultaneously According to product description taking dose) and azithromycin (with reference to azithromycin prescribed dose), azithromycin divides with FUKE QIANJIN PIAN Open and take, differ about 2 hours time.

Matched group: give prednisone sheet 30～50mg and play decoction being taken at a draught morning, subtract 2.5mg after 2 months every other week, until drug withdrawal.Join simultaneously Gastric mucosa protective agent etc. is taken in conjunction.

Observation of curative effect: 3 months be a course for the treatment of.Continuous use observed the symptoms after 3 courses for the treatment of, sign improves situation and bad Reaction.

Result of the test: curative effect aspect,

Matched group (10 example) clinical recovery 1 example (10%), 2 examples that are almost recovered (20%), effective 3 examples (30%), take a turn for the better 3 examples (30%), invalid 1 example (10%).

Treatment group (10 example) clinical recovery 1 example (10%), 3 examples that are almost recovered (30%), effective 5 examples (50%), take a turn for the better 1 example (20%), invalid 0 example (0%).Treatment group shortsighted view is imitated 10 days.Treatment group 10 example check thymus, congested, edema situation significantly changes Kind, thymus organ coefficient replys normal level substantially.

Treatment group cure-remarkable-effectiveness rate, effective percentage are above matched group, P ＜ 0.05, have statistical significance.

Chinese medicine composition of the present invention and being used in combination of azithromycin substantially can improve thymus congestion and edema by targeting, are breast The disease treatment that gland is relevant can be sought drug combination mechanism.

Claims

1. gynecological's prescriptions worth thousand gold compositions combined with antibiotic application in terms of preparation treatment disease of thymus gland medicine, it is characterised in that Described disease of thymus gland is thymus hyperemia, edema and/or hypertrophy disease；Described antibiotic is azithromycin；Described gynecological a thousand pieces of gold The active component of side's compositions is made up of Radix Flemingiae Philippinensis, Herba Andrographis, Radix Rosae Laevigatae, Caulis Mahoniae, Fructus Zanthoxyli Dissiti, Caulis Spatholobi, Radix Angelicae Sinensis and Radix Codonopsis.

The most according to claim 1, gynecological's prescriptions worth thousand gold compositions combined with antibiotic reduces thymus organ index medicine side in preparation The application in face.

Gynecological the most according to claim 1 or claim 2 prescriptions worth thousand gold compositions combined with antibiotic treats the disease relevant to thymus in preparation Application in terms of medicine.

Application the most according to claim 1 and 2, in described Chinese medicine composition, Radix Angelicae Sinensis, Radix Codonopsis, Herba Andrographis and Fructus Zanthoxyli Dissiti Incorporation is respectively the 9% of medical material gross weight；The incorporation of Radix Rosae Laevigatae, Caulis Spatholobi, Caulis Mahoniae and Radix Flemingiae Philippinensis is respectively medical material gross weight 16%。

Application the most according to claim 3, in described Chinese medicine composition, the incorporation of Radix Angelicae Sinensis, Radix Codonopsis, Herba Andrographis and Fructus Zanthoxyli Dissiti Amount is respectively the 9% of medical material gross weight；The incorporation of Radix Rosae Laevigatae, Caulis Spatholobi, Caulis Mahoniae and Radix Flemingiae Philippinensis is respectively the 16% of medical material gross weight.