CN101856381A - Preparation method and quality control method for medicinal preparation for treating women climacteric syndrome - Google Patents
Preparation method and quality control method for medicinal preparation for treating women climacteric syndrome Download PDFInfo
- Publication number
- CN101856381A CN101856381A CN200910020439A CN200910020439A CN101856381A CN 101856381 A CN101856381 A CN 101856381A CN 200910020439 A CN200910020439 A CN 200910020439A CN 200910020439 A CN200910020439 A CN 200910020439A CN 101856381 A CN101856381 A CN 101856381A
- Authority
- CN
- China
- Prior art keywords
- solution
- preparation
- vitamin
- reference substance
- need testing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 35
- 208000011580 syndromic disease Diseases 0.000 title claims abstract description 22
- 238000003908 quality control method Methods 0.000 title claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 31
- 239000003814 drug Substances 0.000 claims abstract description 30
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- 238000012360 testing method Methods 0.000 claims description 25
- 239000000047 product Substances 0.000 claims description 22
- 239000000706 filtrate Substances 0.000 claims description 20
- 235000019359 magnesium stearate Nutrition 0.000 claims description 19
- 239000013558 reference substance Substances 0.000 claims description 18
- 230000008569 process Effects 0.000 claims description 17
- 238000002156 mixing Methods 0.000 claims description 15
- JZRWCGZRTZMZEH-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 claims description 15
- 229930003270 Vitamin B Natural products 0.000 claims description 14
- 235000019156 vitamin B Nutrition 0.000 claims description 14
- 239000011720 vitamin B Substances 0.000 claims description 14
- TZJALUIVHRYQQB-XFDQAQKOSA-N Icariin Natural products O(C)c1ccc(C2=C(O[C@H]3[C@@H](O)[C@H](O)[C@@H](O)[C@H](C)O3)C(=O)c3c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O4)c(C/C=C(\C)/C)c3O2)cc1 TZJALUIVHRYQQB-XFDQAQKOSA-N 0.000 claims description 13
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 13
- TZJALUIVHRYQQB-XLRXWWTNSA-N icariin Chemical compound C1=CC(OC)=CC=C1C1=C(O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)C(=O)C2=C(O)C=C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C(CC=C(C)C)=C2O1 TZJALUIVHRYQQB-XLRXWWTNSA-N 0.000 claims description 13
- TZJALUIVHRYQQB-UHFFFAOYSA-N icariine Natural products C1=CC(OC)=CC=C1C1=C(OC2C(C(O)C(O)C(C)O2)O)C(=O)C2=C(O)C=C(OC3C(C(O)C(O)C(CO)O3)O)C(CC=C(C)C)=C2O1 TZJALUIVHRYQQB-UHFFFAOYSA-N 0.000 claims description 13
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 13
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 13
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 13
- 229920002472 Starch Polymers 0.000 claims description 12
- 239000008107 starch Substances 0.000 claims description 12
- 235000019698 starch Nutrition 0.000 claims description 12
- 239000000463 material Substances 0.000 claims description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 10
- 239000002775 capsule Substances 0.000 claims description 10
- 239000000945 filler Substances 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- RBCOYOYDYNXAFA-UHFFFAOYSA-L (5-hydroxy-4,6-dimethylpyridin-3-yl)methyl phosphate Chemical compound CC1=NC=C(COP([O-])([O-])=O)C(C)=C1O RBCOYOYDYNXAFA-UHFFFAOYSA-L 0.000 claims description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 239000008187 granular material Substances 0.000 claims description 6
- 239000000314 lubricant Substances 0.000 claims description 6
- 239000011734 sodium Substances 0.000 claims description 6
- 229910052708 sodium Inorganic materials 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 229920001353 Dextrin Polymers 0.000 claims description 5
- 239000004375 Dextrin Substances 0.000 claims description 5
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 5
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 5
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 5
- 235000019425 dextrin Nutrition 0.000 claims description 5
- 239000008101 lactose Substances 0.000 claims description 5
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 238000003556 assay Methods 0.000 claims description 4
- 238000001514 detection method Methods 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 239000000377 silicon dioxide Substances 0.000 claims description 4
- 239000006228 supernatant Substances 0.000 claims description 4
- 239000007916 tablet composition Substances 0.000 claims description 4
- 239000012567 medical material Substances 0.000 claims description 3
- YEZWWUMWIFKEQM-UHFFFAOYSA-N O.OC.ClC(Cl)Cl.CCOC(C)=O Chemical compound O.OC.ClC(Cl)Cl.CCOC(C)=O YEZWWUMWIFKEQM-UHFFFAOYSA-N 0.000 claims description 2
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 claims description 2
- 239000000741 silica gel Substances 0.000 claims description 2
- 229910002027 silica gel Inorganic materials 0.000 claims description 2
- 239000007921 spray Substances 0.000 claims description 2
- 238000004809 thin layer chromatography Methods 0.000 claims description 2
- 238000005303 weighing Methods 0.000 claims description 2
- 238000000605 extraction Methods 0.000 abstract description 14
- 238000005516 engineering process Methods 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 2
- 241000446313 Lamella Species 0.000 abstract 1
- 239000007963 capsule composition Substances 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 238000000691 measurement method Methods 0.000 abstract 1
- 238000005457 optimization Methods 0.000 abstract 1
- 238000012216 screening Methods 0.000 abstract 1
- 229940079593 drug Drugs 0.000 description 9
- 210000003734 kidney Anatomy 0.000 description 8
- 239000002245 particle Substances 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 6
- 238000009472 formulation Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 230000007812 deficiency Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 3
- 238000012850 discrimination method Methods 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 235000019634 flavors Nutrition 0.000 description 3
- 206010025482 malaise Diseases 0.000 description 3
- 230000005180 public health Effects 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 241000721047 Danaus plexippus Species 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229940011871 estrogen Drugs 0.000 description 2
- 239000000262 estrogen Substances 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000004904 shortening Methods 0.000 description 2
- 238000011003 system suitability test Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000007306 turnover Effects 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 241000201295 Euphrasia Species 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 208000032023 Signs and Symptoms Diseases 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 208000031975 Yang Deficiency Diseases 0.000 description 1
- 208000031971 Yin Deficiency Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 201000003914 endometrial carcinoma Diseases 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 238000002657 hormone replacement therapy Methods 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 230000009245 menopause Effects 0.000 description 1
- 230000004630 mental health Effects 0.000 description 1
- 230000027939 micturition Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 210000000106 sweat gland Anatomy 0.000 description 1
- 230000035900 sweating Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a medicament for treating women climacteric syndrome, which is characterized in that the invention provides a preparation method and a quality control method for a new Chinese medicinal preparation, namely, Gengnianling tablets which are prepared by improving Gengnianling capsule formulations. The preparation method and the quality control method adopt the technical scheme that the optimization and screening are performed in an extraction process; the modern new equipment, new technology and new method are adopted technically, and the Chinese medicinal preparation is suitable for industrial production; and the quality standard study is improved on the basis of the original standard, a lamella identification method and a content measurement method are formulated currently, the quality standard of products is advanced and controlled, and the clinical curative effect is ensured.
Description
One, technical field
The invention belongs to field of traditional Chinese, relate to a kind of Chinese medicine preparation for the treatment of climacteric syndrome preparation method and method of quality control thereof.
Two, background technology
Climacteric syndrome is meant the women before and after the menopause, because of ovarian function fails gradually or lose, causes the decline of estrogen secretion level, thereby a series of syndromes based on autonomic nervous dysfunction's dysbolismus that cause, is common clinical, frequently-occurring disease.Clinical manifestation is mainly hectic fever, sweating, agitation, cardiopalmus, melancholy, insomnia, frequent micturition, headache, osteodynia.According to statistics, the climacteric syndrome sickness rate is more than 80%, and wherein the serious symptom sickness rate accounts for about 30%.Age of onset is generally between 45 years old～55 years old.In recent years, because social competition is fierce day by day, and other society, family factors, its sickness rate has the trend that rises year by year, not only influences ill women's physical and mental health, reduces quality of life, also can cause many families and social problem.
Doctor trained in Western medicine adopts " Hormone Replacement Therapy " to treat more, and this therapy can be alleviated partial symptoms, but takes diseases such as easily causing carcinoma of endometrium, breast carcinoma for a long time, and toxic and side effects is big, and is halted gradually in states such as America and Europes.Chinese medicine is the medical science applied characteristic of China, and the method by determination of treatment based on pathogenesis obtained through differentiation of symptoms and signs has accumulated abundant clinical experience to the treatment of climacteric syndrome.Chinese medicine calls climacteric syndrome " pre-postmenstrual syndromes ", think its main pathogenesis for suffer from a deficiency of the kidney, imbalance of YIN and YANG, the suitable the kidney invigorating and essence nourishing of Therapeutic Principle, YIN and YANG balance regulating.Therefore many clinically employing Chinese prescriptions are treated or are treated this disease based on the Chinese and Western compound preparation of Chinese medicine, at the medication of suffering from a deficiency of the kidney, the kidney invigorating and essence nourishing, kidney qi must be mended, equilibrium between yin and yang, thus illness must heal, and reaches the purpose for the treatment of both the principal and secondary aspects of a disease, and it is good to take safety for a long time, therefore more and more is subjected to the favor of extensive patients.
The climacteric curing capsule is the kind of recording in the 14 in " Drug Standard of Ministry of Public Health of the Peoples Republic of China " Chinese traditional patent formulation preparation, be monarch drug with the Herba Epimedii in the side, invigorating the liver and kidney, hard muscles and bones, supporing yang benefit essence, be aided with the Fructus Ligustri Lucidi nourishing the liver and kidney, black hair makes eye bright, two medicines are the principal agent of tcm clinical practice treatment climacteric syndrome; Select for use oryzanol to regulate vegetative nerve function again, reduce the incretion balance obstacle, improve the psychataxia symptom, vitamin B
1, vitamin B
6Keep homergy, above-mentioned five kinds of Chinese medicine compatibility is played the kidney warming tonifying YIN altogether, and the merit of adjusting and runing yang is used for the treatment of the climacteric syndrome person that belongs to the deficiency of both YIN and YANG.Show according to the pharmacodynamics report: 1. this product has tangible calmness and anticonvulsant action, 2. suppresses the sweat gland excessive secretion, 3. can stimulate adrenal tissue's hypertrophy, improves serum estrogen level, 4. the deficiency of YIN and yang deficiency immunologic function is all had some improvement; Above result of the test shows that this product has therapeutical effect preferably to climacteric syndrome.This product clinical practice for many years, and is safe and effective, so we have carried out further research and development to this kind.
Three, summary of the invention
The objective of the invention is to weak point, carry out rational form improvement, develop climacteric spirit sheet at the climacteric curing capsule.Consider in the agent of climacteric curing capsule and occupy significant proportion owing to the Chinese medicine dried cream powder, the viscosity and the hygroscopicity of mixing back medicated powder are strong, and be wayward in the production, exists medicine that moisture absorption bonding easily takes place in addition behind the filled capsules, thereby influence clinical efficacy.Therefore, be tablet with its form improvement, it is good to give full play to tablet stability, and the bioavailability height is taken and convenient carrying, for this prescription has increased a novel form again, adapts to the requirement of vast climacteric syndrome patient to different dosage form.
Another object of the present invention is to be optimized on extraction process and to screen, adopt modern new equipment, new technique, new method technically, worked out the production technology of reasonable science, be fit to industrialized great production, put forward process conditions such as different amount of water as preferred water outlet, make extraction process clearer and more definite; Aspect preparation technique, adopt the one-step palletizing technology, mixings, granulations, a dry step are finished, the realization fluidized drying, matter is heat passage soon, can the side of assurance in content of effective; Reduced operation and turnover, effectively prevented to pollute; The shortening production cycle was kept to 1 day from 4～5 days, and can save energy 40%～50%.
Another purpose of the present invention is to adopt different auxiliary material to screen in the tablet formulation process, preferably is beneficial to the adjuvant of tablet molding, has guaranteed the stability of tablet.Wherein said adjuvant comprises filler, disintegrating agent and lubricant, and wherein filler is selected from a kind of of starch, dextrin, lactose or two kinds or three kinds, and its consumption is 1%～15%; Disintegrating agent is selected from a kind of of microcrystalline Cellulose, carboxymethyl starch sodium or two kinds, and its consumption is 2%～8%; Lubricant is selected from a kind of of magnesium stearate, sodium lauryl sulphate or two kinds, and its consumption is 0.4%～1.2%.
A further object of the present invention is that preparation has been carried out detailed deep quality standard research, improves on the basis of primary standard.Under the 14 climacteric curing capsule quality standard item that records of former " Drug Standard of Ministry of Public Health of the Peoples Republic of China " Chinese traditional patent formulation preparation only the thin layer of rationalization discriminating and Herba Epimedii differentiate, do not establish the assay item, this product is in development process, the Chinese crude drug of respectively distinguishing the flavor of in the prescription has all been carried out deep Study on Identification, improve the thin layer discrimination method of Herba Epimedii, set up icariin, vitamin B
1, vitamin B
6With the content assaying method of oryzanol, can control the quality of this product comprehensively and effectively, guarantee clinical efficacy.
Technical scheme of the present invention is: with the five kinds of Chinese medicine in the former climacteric curing capsule prescription, get Herba Epimedii and Fructus Ligustri Lucidi, decoct with water respectively three times, each 2 hours, collecting decoction filtered, filtrate is concentrated into the thick paste that relative density is 1.16～1.30 (60 ℃), with oryzanol, vitamin B
1, vitamin B
6, right amount of auxiliary materials, one-step palletizing or drying are pulverized, and granulate, the gained granule adds right amount of auxiliary materials, mixing is pressed into 1000, the bag film-coat, promptly.
In extraction dried particles of the present invention, add 1%～15% starch or dextrin or lactose, add 2%～8% microcrystalline Cellulose or carboxymethyl starch sodium, mixing sieves, and adds 0.4%～1.2% magnesium stearate or sodium lauryl sulphate, mixing, tabletting is tablet of the present invention.
Using method of the present invention: oral, one time 1～2, three times on the one.
The invention has the beneficial effects as follows:
(1) tablet of the present invention is the kind of carrying out form improvement on the basis of former climacteric curing capsule agent, compare with capsule, tablet stability is good, the bioavailability height, take and easy to carry, increased a novel form again for this prescription simultaneously, adapted to the requirement of vast climacteric syndrome patient different dosage form.
(2) preparation technology is optimized and screen.On extraction process, not marked extraction process condition in the primary standard is investigated, and determined optimum extraction process, make manufacturing condition clearer and more definite; Again preparation process is studied, has been determined optimal formulation technology, and adopt the one-step palletizing technology, mixings, granulations, a dry step are finished, the realization fluidized drying, matter is heat passage soon, can the side of assurance in content of effective; Reduced operation and turnover, effectively prevented to pollute; The shortening production cycle was kept to 1 day from 4～5 days, and can save energy 40%～50%.
(3) carried out improving and raising of quality standard.Under the 14 climacteric curing capsule quality standard item that records of former " Drug Standard of Ministry of Public Health of the Peoples Republic of China " Chinese traditional patent formulation preparation only the thin layer of rationalization discriminating and Herba Epimedii differentiate, do not establish the assay item, this product is in development process, the Chinese crude drug of respectively distinguishing the flavor of in the prescription has all been carried out deep Study on Identification, improve the thin layer discrimination method of Herba Epimedii, set up icariin, vitamin B
1, vitamin B
6With the content assaying method of oryzanol, can control the quality of this product comprehensively and effectively, guarantee clinical efficacy.
Below by test the adjuvant in the above-mentioned tablet formulation process is further screened and optimizes.
1. the consumption of magnesium stearate is investigated
Get the granule that makes, add magnesium stearate in 0.4%, 0.7%, 1.0% ratio respectively, other adds 4% microcrystalline Cellulose, mixing, and tabletting the results are shown in Table 1 respectively.
Table 1 magnesium stearate addition is to the influence of tablet weight variation
The magnesium stearate addition is 0.4% o'clock, and tablet weight variation is bigger, and 1 overrun is arranged; The magnesium stearate addition is 0.7% o'clock, and tablet weight variation is still bigger, and the magnesium stearate consumption is 1.0% o'clock label smooth surface, smooth, no sliver phenomenon, in three kinds of ratios add magnesium stearate press disintegration of tablet time limit no significant difference, so the magnesium stearate consumption is 1%.
2. the consumption of microcrystalline Cellulose is investigated
Get the granule that makes, add microcrystalline Cellulose in 2%, 3%, 4% ratio respectively, other adds 1% magnesium stearate, mixing, and tabletting the results are shown in Table 2 respectively.
Table 2 microcrystalline Cellulose addition is to the influence of label
According to result of the test, select for use the microcrystalline Cellulose of 1% magnesium stearate and 3～4% good as the label quality that adjuvant makes, be beneficial to coating, and few to the heavy increment of sheet.So determine that supplementary product consumption is that magnesium stearate is 1%, the microcrystalline Cellulose consumption is 3～4%.Be that each recipe quantity (1000) is used magnesium stearate 3g, microcrystalline Cellulose 9～12g.
Four, the specific embodiment
Be described in further detail below by the extraction formulation method and the method for quality control of specific embodiment climacteric spirit sheet.
Embodiment 1:
With the five kinds of Chinese medicine in the former prescription, Herba Epimedii decocts with water three times, and each 2 hours, add 14 times of water gagings for the first time, add 12 times of water gagings for the second time, add 10 times of water gagings for the third time, collecting decoction filters, and filtrate is concentrated into the thick paste that relative density is 1.16～1.30 (60 ℃); Fructus Ligustri Lucidi decocts with water three times, and each 2 hours, add 8 times of water gagings for the first time, add 6 times of water gagings for the second time, add 6 times of water gagings for the third time, collecting decoction filters, filtrate is concentrated into the thick paste that relative density is 1.16～1.30 (60 ℃), and above-mentioned two kinds of thick pastes merge, with oryzanol, vitamin B
1, vitamin B
6, starch is an amount of, one-step palletizing promptly gets extraction dried particles of the present invention.
Embodiment 2:
With the five kinds of Chinese medicine in the former prescription, Herba Epimedii decocts with water three times, 2 hours for the first time, 2 hours for the second time, 1 hour for the third time, add for the first time 14 times of water gagings, for the second time add 12 times of water gagings, add 10 times of water gagings for the third time, collecting decoction, filter, filtrate is concentrated into the thick paste that relative density is 1.16～1.30 (60 ℃); Fructus Ligustri Lucidi decocts with water three times, 2 hours for the first time, 2 hours for the second time, 1 hour for the third time, add for the first time 8 times of water gagings, for the second time add 6 times of water gagings, add 6 times of water gagings for the third time, collecting decoction, filter, filtrate is concentrated into the thick paste that relative density is 1.16～1.30 (60 ℃), and above-mentioned two kinds of thick pastes merge, with oryzanol, vitamin B
1, vitamin B
6, dextrin is an amount of, one-step palletizing promptly gets extraction dried particles of the present invention.
Embodiment 3:
With the five kinds of Chinese medicine in the former prescription, Herba Epimedii decocts with water three times, and each 2 hours, add 14 times of water gagings for the first time, add 12 times of water gagings for the second time, add 10 times of water gagings for the third time, collecting decoction filters, and filtrate is concentrated into the thick paste that relative density is 1.16～1.30 (60 ℃); Fructus Ligustri Lucidi decocts with water three times, and each 2 hours, add 8 times of water gagings for the first time, add 6 times of water gagings for the second time, add 6 times of water gagings for the third time, collecting decoction filters, filtrate is concentrated into the thick paste that relative density is 1.16～1.30 (60 ℃), and above-mentioned two kinds of thick pastes merge, with oryzanol, vitamin B
1, vitamin B
6, lactose is an amount of, one-step palletizing promptly gets extraction dried particles of the present invention.
Embodiment 4:
To add the 12g microcrystalline Cellulose in any extraction dried particles in the various embodiments described above, mixing sieves, and adds the 3g magnesium stearate, mixing, and tabletting is tablet of the present invention.
Embodiment 5:
To add the 12g microcrystalline Cellulose in any extraction dried particles in the various embodiments described above, mixing sieves, and adds the 1.2g magnesium stearate, mixing, and tabletting is tablet of the present invention.
Embodiment 6:
To add the 6g carboxymethyl starch sodium in any extraction dried particles in the various embodiments described above, mixing sieves, and adds the 3g sodium lauryl sulphate, mixing, and tabletting is tablet of the present invention.
Embodiment 7:
In the quality control of the present invention, the medical material of respectively distinguishing the flavor of in the prescription is all carried out more deep research, improved the thin layer discrimination method of Herba Epimedii, set up the content assaying method of monarch drug icariin and all chemical drugss.
(1) thin layer of Herba Epimedii is differentiated as follows:
Get 10 of this product, porphyrize is got 0.6g, puts in the 50ml tool plug conical flask, adds methanol 10ml, and supersound process 30 minutes filters, and discards filtrate just, gets subsequent filtrate as need testing solution.Other gets Herba Epimedii control medicinal material coarse powder 0.6g, adds methanol 10ml, and supersound process 30 minutes filters, and discards filtrate just, gets subsequent filtrate medical material solution in contrast.Get the icariin reference substance again, add methanol and make the solution that every 1ml contains 0.5mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005), draw need testing solution 5 μ l, control medicinal material solution 5 μ l and reference substance solution 4 μ l, put respectively on same silica gel g thin-layer plate, (15: 40: 22: 10) placing stratified lower floor solution below 10 ℃ was developing solvent with chloroform-ethyl acetate-methanol-water, launch in the refrigerator, take out, dry, spray is with 10% ethanol solution of sulfuric acid, and it is clear to be heated to the speckle colour developing at 105 ℃.In the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color.
(2) assay is as follows:
(1) icariin is measured according to high performance liquid chromatography (an appendix VI of Chinese Pharmacopoeia version in 2005 D).
Chromatographic condition and system suitability test are filler with the octadecylsilane chemically bonded silica; Acetonitrile-water (29: 71) is a mobile phase; The detection wavelength is 270nm.Number of theoretical plate calculates by the icariin peak should be not less than 3000.
It is an amount of that the icariin reference substance is got in the preparation of reference substance solution, and accurate the title decides, and adds 70% methanol and makes the solution that every 1ml contains icariin 40 μ g, in contrast product solution.
This product under the weight differential item is got in the preparation of need testing solution, and porphyrize is got about 0.2g, and accurate the title decides, and puts in the 50ml measuring bottle, add the about 40ml of 70% methanol, supersound process 30 minutes is put coldly, supplies solvent to scale, shake up, filter, discard filtrate just, get subsequent filtrate as need testing solution.
Accurate respectively reference substance solution and each the 20 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.
(2) vitamin B
1, vitamin B
6Measure according to high performance liquid chromatography (an appendix VI of Chinese Pharmacopoeia version in 2005 D).
Chromatographic condition and system suitability test are filler with the octadecylsilane chemically bonded silica; 0.05mol/L (triethylamine is transferred pH3.5)-water (20: 80) is mobile phase to citric acid; The detection wavelength is 275nm.Number of theoretical plate is pressed vitamin B
6The peak calculates should be not less than 2000, vitamin B
1, vitamin B
6The two separating degree is greater than 1.5.
The preparation of reference substance solution takes by weighing vitamin B respectively
1, vitamin B
6Reference substance is an amount of, adds water and makes every 1ml and contain vitamin B
1, vitamin B
6The solution of each 100 μ g, product solution in contrast.
This product under the weight differential item is got in the preparation of need testing solution, and porphyrize is got about 0.15g, the accurate title, decide, put in the 100ml tool plug conical flask, precision adds entry 50ml, and precision is weighed, supersound process 30 minutes, put coldly, supply solvent, shake up to original weight, centrifugal (3000 rev/mins) 5 minutes get supernatant as need testing solution.
Accurate respectively reference substance solution and each the 20 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.
(3) oryzanol is measured according to spectrophotography (an appendix V of Chinese Pharmacopoeia version in 2005 A).
Algoscopy is got this product under the weight differential item, and porphyrize is got about 0.1g, the accurate title, decide, and puts in the 25ml measuring bottle, adds normal heptane 20ml, supersound process 20 minutes is put coldly, adds normal heptane and is diluted to scale, shake up, centrifugal (3000 rev/mins) 5 minutes, precision are measured supernatant 2ml and are put in the 25ml measuring bottle, add normal heptane and are diluted to scale, shake up, as need testing solution.According to spectrophotography (an appendix V of Chinese Pharmacopoeia version in 2005 A), measure trap at the wavelength place of 315nm.Press the absorptance of oryzanol
Be 350 calculating, promptly.
Claims (7)
1. Chinese medicine preparation for the treatment of climacteric syndrome, it is characterized in that its preparation method is with the five kinds of Chinese medicine in the former climacteric curing capsule prescription, get Herba Epimedii and Fructus Ligustri Lucidi, decoct with water respectively three times, each 2 hours, collecting decoction filtered, filtrate is concentrated into the thick paste that relative density is 1.16～1.30 (60 ℃), with oryzanol, vitamin B
1, vitamin B
6, right amount of auxiliary materials, one-step palletizing or drying are pulverized, and granulate, and make granule and add right amount of auxiliary materials, mixing is pressed into 1000, the bag film-coat, promptly.
2. the described a kind of Chinese medicine preparation for the treatment of climacteric syndrome of claim 1 is characterized in that Herba Epimedii decocts with water three times in the preparation process, each 2 hours, adds 8～16 times of water gagings at every turn.
3. the described a kind of Chinese medicine preparation for the treatment of climacteric syndrome of claim 1 is characterized in that Fructus Ligustri Lucidi decocts with water three times in the preparation process, each 2 hours, adds 6～12 times of water gagings at every turn.
4. the described a kind of Chinese medicine preparation for the treatment of climacteric syndrome of claim 1 is characterized in that wherein said adjuvant comprises filler, disintegrating agent and lubricant, and wherein filler is selected from a kind of of starch, dextrin, lactose or two kinds or three kinds; Disintegrating agent is selected from one or both of microcrystalline Cellulose, carboxymethyl starch sodium; Lubricant is selected from one or both of magnesium stearate, sodium lauryl sulphate.
5. the described a kind of Chinese medicine preparation for the treatment of climacteric syndrome of claim 1, it is characterized in that in the tablet formulation process that as starch, dextrin, the lactose of filler, its consumption is 1%-15%, as microcrystalline Cellulose, the carboxymethyl starch sodium of disintegrating agent, its consumption is 2%-8%; Lubricant is selected from magnesium stearate, sodium lauryl sulphate, and its consumption is 0.4%-1.2%.
6. a kind of Chinese medicine preparation for the treatment of climacteric syndrome as claimed in claim 1, it is characterized in that in the tablet formulation process the starch that is as filler, its consumption is 1～5%, as disintegrating agent is carboxymethyl starch sodium, its consumption is 3～4%, as lubricant be magnesium stearate, its consumption is 1.0%.
7. a kind of Chinese medicine preparation for the treatment of climacteric syndrome as claimed in claim 1 is characterized in that its quality control index is:
(1) thin layer of Herba Epimedii is differentiated as follows:
Get 10 of this product, porphyrize, get 0.6g, put in the 50ml tool plug conical flask, add methanol 10ml, supersound process 30 minutes, filter, discard filtrate just, get subsequent filtrate as need testing solution, other gets Herba Epimedii control medicinal material coarse powder 0.6g, add methanol 10ml, supersound process 30 minutes filters, and discards filtrate just, get subsequent filtrate medical material solution in contrast, get the icariin reference substance again, add methanol and make the solution that every 1ml contains 0.5mg, in contrast product solution, test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2005 B), draw need testing solution 5 μ l, control medicinal material solution 5 μ l and reference substance solution 4 μ l put respectively on same silica gel g thin-layer plate, and (15: 40: 22: 10) placing stratified lower floor solution below 10 ℃ was developing solvent with chloroform-ethyl acetate-methanol-water, launch in the refrigerator, take out, dry, spray is with 10% ethanol solution of sulfuric acid, it is clear to be heated to speckle colour developing at 105 ℃, in the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color;
(2) assay is as follows:
(1) icariin:
According to high performance liquid chromatography, be filler with the octadecylsilane chemically bonded silica; Acetonitrile-water (29: 71) is a mobile phase; The detection wavelength is 270nm; Number of theoretical plate calculates by the icariin peak should be not less than 3000;
The preparation of reference substance solution: it is an amount of to get the icariin reference substance, and accurate the title decides, and adds 70% methanol and makes the solution that every 1ml contains icariin 40 μ g, in contrast product solution;
The preparation of need testing solution: get this product under the weight differential item, porphyrize is got about 0.2g, and accurate the title decides, and puts in the 50ml measuring bottle, add the about 40ml of 70% methanol, supersound process 30 minutes is put coldly, supplies solvent to scale, shake up, filter, discard filtrate just, get subsequent filtrate as need testing solution;
Algoscopy: accurate respectively reference substance solution and each 20 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly;
(2) vitamin B
1, vitamin B
6:
According to high performance liquid chromatography, be filler with the octadecylsilane chemically bonded silica; 0.05mol/L (triethylamine is transferred pH3.5)-water (20: 80) is mobile phase to citric acid; The detection wavelength is 275nm.Number of theoretical plate is pressed vitamin B
6The peak calculates should be not less than 2000, vitamin B
1, vitamin B
6The two separating degree is greater than 1.5;
The preparation of reference substance solution: take by weighing vitamin B respectively
1, vitamin B
6Reference substance is an amount of, adds water and makes every 1ml and contain vitamin B
1, vitamin B
6The solution of each 100 μ g, product solution in contrast;
The preparation of need testing solution: get this product under the weight differential item, porphyrize is got about 0.15g, the accurate title, decide, put in the 100ml tool plug conical flask, precision adds entry 50ml, and precision is weighed, supersound process 30 minutes, put coldly, supply solvent, shake up to original weight, centrifugal (3000 rev/mins) 5 minutes get supernatant as need testing solution;
Algoscopy: accurate respectively reference substance solution and each 20 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly;
(3) oryzanol:
Get this product under the weight differential item, porphyrize is got about 0.1g, the accurate title, decide, and puts in the 25ml measuring bottle, adds normal heptane 20ml, supersound process 20 minutes is put coldly, adds normal heptane and is diluted to scale, shake up, centrifugal (3000 rev/mins) 5 minutes, precision is measured supernatant 2ml and is put in the 25ml measuring bottle, add normal heptane and be diluted to scale, shake up, as need testing solution, according to spectrophotography (an appendix V of Chinese Pharmacopoeia version in 2005 A), measure trap at the wavelength place of 315nm, press the absorptance of oryzanol
Be 350 calculating, promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910020439A CN101856381A (en) | 2009-04-09 | 2009-04-09 | Preparation method and quality control method for medicinal preparation for treating women climacteric syndrome |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910020439A CN101856381A (en) | 2009-04-09 | 2009-04-09 | Preparation method and quality control method for medicinal preparation for treating women climacteric syndrome |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101856381A true CN101856381A (en) | 2010-10-13 |
Family
ID=42942684
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200910020439A Pending CN101856381A (en) | 2009-04-09 | 2009-04-09 | Preparation method and quality control method for medicinal preparation for treating women climacteric syndrome |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101856381A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104198645A (en) * | 2014-09-17 | 2014-12-10 | 上海海虹实业(集团)巢湖今辰药业有限公司 | Method for identifying epimedium herb in climacterium capsule |
| CN104198616A (en) * | 2014-09-17 | 2014-12-10 | 上海海虹实业(集团)巢湖今辰药业有限公司 | Method for determining content of icariin in climacterium capsule |
| CN105769790A (en) * | 2016-03-15 | 2016-07-20 | 山东仁和堂药业有限公司 | Oryznol tablets for treating premenstrual tension and climacteric syndromes and preparation process thereof |
| CN109061028A (en) * | 2018-08-16 | 2018-12-21 | 河北维尔利动物药业集团有限公司 | Chinese medicine chastity lotus increases and exempts from oral solution quality determining method |
-
2009
- 2009-04-09 CN CN200910020439A patent/CN101856381A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104198645A (en) * | 2014-09-17 | 2014-12-10 | 上海海虹实业(集团)巢湖今辰药业有限公司 | Method for identifying epimedium herb in climacterium capsule |
| CN104198616A (en) * | 2014-09-17 | 2014-12-10 | 上海海虹实业(集团)巢湖今辰药业有限公司 | Method for determining content of icariin in climacterium capsule |
| CN105769790A (en) * | 2016-03-15 | 2016-07-20 | 山东仁和堂药业有限公司 | Oryznol tablets for treating premenstrual tension and climacteric syndromes and preparation process thereof |
| CN109061028A (en) * | 2018-08-16 | 2018-12-21 | 河北维尔利动物药业集团有限公司 | Chinese medicine chastity lotus increases and exempts from oral solution quality determining method |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101856381A (en) | Preparation method and quality control method for medicinal preparation for treating women climacteric syndrome | |
| CN103239590A (en) | Traditional Chinese medicine composition as well as preparation and application thereof | |
| CN101890087A (en) | Composition containing coptis root, rhubarb and baikal skullcap root | |
| CN101829216A (en) | Preparation method and quality control method of traditional Chinese medicine preparation for treating bronchitis and bronchial asthma | |
| CN101972297A (en) | Liver health tablet | |
| AU2007357043B2 (en) | Pharmaceutical composition for regulating blood sugar and fat, preparation and use thereof | |
| CN1226033C (en) | Method for preparing traditional Chinese medicine concentrated pill | |
| CN1879850A (en) | Capsule with hairy vein agrimony and arenobufagin, its preparation process and quality control method | |
| CN1876000B (en) | Preparation process of 'Yan Lu Ru Kang' pharmaceutical preparation for treating mammary gland hyperplasia | |
| CN1958005A (en) | Combination of Chinese traditional medicine, preparation method, and quality control method | |
| CN101485736B (en) | Medicament composition with stone-eliminating and expelling functions and preparation method thereof | |
| CN102309543B (en) | Compound salvia miltiorrhiza concentrated preparation and preparation and detection method thereof | |
| CN100515476C (en) | Compound capsule with pseudo-ginseng and Chinese fanpalm seed, its preparation process and quality control method | |
| CN100411616C (en) | Methocarbamol dispersion tablet | |
| CN1887324B (en) | Chinese medicine composition for treating liver and kidney defect, and its preparation process and analysis method | |
| CN109045240B (en) | Traditional Chinese medicine composition of Gaocheng preparation, preparation method, detection method and application thereof | |
| CN1923263B (en) | Traditional Chinese medicine composition, its preparing method and quality controlling means | |
| CN106692706A (en) | Preparation method for medicine used for treating vertigo | |
| CN106466396B (en) | Gynaecologic menstruation regulating sustained-release dropping pill and preparation method thereof | |
| CN105012522A (en) | Kidney-nourishing brain-fortifying traditional Chinese medicine, preparation method and purpose | |
| CN1965951A (en) | Blood tonic capsule having ass hide and method for preparing same | |
| CN1994426B (en) | Preparation method, and identification and assaying method of 'Sheng Mai' soft capsule | |
| CN1331465C (en) | Blood stasis dispelling dripping pills for treating coronary heart disease, angina pectoris and hyperlipemia and preparation process thereof | |
| CN1325082C (en) | Traditional Chinese medicine composition, prepn. method and quality control method therefor | |
| CN1695713B (en) | A kind of medicine for treating diabetes and its preparation and quality control method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20101013 |