Chinese medicine composition of treatment dysmenorrhes, menoxenia and preparation method thereof
Technical field
The present invention relates to a kind of Chinese medicine composition, relate in particular to a kind of Chinese medicine composition for the treatment of dysmenorrhes or menoxenia and preparation method thereof, belong to the field of Chinese medicines.
Background technology
According to statistics, China women of child-bearing age account for 1/4th of population, be about 34,185 ten thousand people, calculate by the minimum sickness rate 33.19% of dysmenorrhea, dysmenorrhea patient is about 11,346 ten thousand people, certain transnational survey institute shows coastal 17 large-and-medium size cities of China result that investigates: the annual capacity in China regulating menstruation market is 5,100,000,000 yuan, and wherein this plate of dysmenorrhea has occupied most market shares.The investigation data shows, the crowd who the pain related symptoms is arranged and take the menstruction regulating and pain relieving product accounts for 40%, and the crowd who does not take the menstruction regulating and pain relieving series products is 43%.
Along with the raising day by day to self health concerns degree of the reform of China's Health care system and female consumer, the market of gynecological's quasi drugs sharply enlarges.But because of consumer to the information attention of dysmenorrhea series products not initiatively, the exploitation degree of dysmenorrhea series products is not high at present.Western medicine mostly is the anti-inflammatory analgetic class, and side effect is big, is in a disadvantageous position in market sale.Chinese medicine has that property of medicine gentleness, side effect are little, the characteristics for the treatment of both the principal and secondary aspects of a disease, the status that is in a leading position in the selling market.
This shows that dysmenorrhea market exists very big potentiality, particularly in women medicine kind, focus mostly on enrich blood, the looks improving and the skin nourishing field, the regulating menstruation product is also few, and Chinese patent medicine regulating menstruation class is particularly treated the product of the class of primary dysmenorrhea and made a new start very few.
At present, YUEYUESHU board TONGJINGBAO KELI is enjoyed quite high reputation and popularity in female consumer, and the coverage rate of domestic market is 98%, and the comprehensive market occupation rate reaches 11.98%.This drug main will be made by Radix Angelicae Sinensis, Cortex Cinnamomi, Flos Carthami, Radix Salviae Miltiorrhizae, Rhizoma Corydalis, Oletum Trogopterori, rhizoma sparganic, Rhizoma Curcumae and the Radix Aucklandiae, for dysmenorrhes, menoxenia, chronic basin glue inflammation etc. has certain curative effect, but because this official ceremonial dress is longer with the time, and dosage is big, and consumer can disposablely not buy, and can select single box to buy, thereby purchase frequency is higher in a short time, consumer more wish to buy carry, taking convenience, taking dose is little, toxic and side effects is little, the product for the treatment of both the principal and secondary aspects of a disease.
At present, the treatment dysmenorrhea is abroad mainly based on chemical medicine, and domestic Chinese medicine has occupied about 50% the market share.But the new drug development cycle based on chemosynthesis is long, success rate is low, difficulty is big, expense is high, and toxic and side effects is bigger, medicine source property illness is increasing, be easy to generate Drug resistance and drug dependence, some worldwide difficult and complicated illness are seemed unable to do what one wishes, new drug (NEC) cost increases, costs an arm and a leg in addition, the benefit phase is short, causes western medicine and medical practitioners more and more can not satisfy the human health demand fully, forces people to produce the strong desire of " back to nature "; On the other hand, because the improvement of living condition, living environment improves day by day to the requirement of drug effectiveness, safety, " back to nature " become a kind of certainty of social development, and the research and development natural drug has become the new trend of current international medical science development.
Primary dysmenorrhea is meant and can not find the obvious pathological changes of reproductive system, but dysmenorrhea former because of some thereby that cause takes place, and primary dysmenorrhea is most commonly in the unmarried women colony that does not produce below 25 years old.In recent years, report that abroad women's sickness rate of primary dysmenorrhea before 19 years old obviously increases.The Chinese medicine medicine for the treatment of primary dysmenorrhea in the market is few, and curative effect is very indefinite
Summary of the invention
The present invention's technical problem at first to be solved is to overcome the deficiencies in the prior art, a kind of effectively Chinese medicine composition of menstruction regulating and pain relieving is provided, dysmenorrhea can effectively be treated or control to this Chinese medicine composition, has advantages such as toxic and side effects is little, clinical practice safety, convenience.
The present invention's technical problem at first to be solved is achieved through the following technical solutions:
A kind of Chinese medicine composition for the treatment of primary dysmenorrhea, menoxenia is mainly made by following bulk drugs: Radix Bupleuri 12-13 part, Radix Angelicae Sinensis 12-13 part, Radix Paeoniae Alba 12-13 part, Rhizoma Corydalis 12-13 part, Rhizoma Cyperi 12-13 part, Radix Linderae 10-11 part, Rhizoma Atractylodis Macrocephalae 5-6 part, Radix Glycyrrhizae 5-6 part, Myrrha 5-6 part, Cortex Cinnamomi 5-6 part, Fructus Amomi 3-4 part and Radix Dipsaci 4-5 part;
Preferably, the weight portion of each crude drug is: 4.5 parts of 12.5 parts of Radix Bupleuri, 12.5 parts of Radix Angelicae Sinensis, 12.5 parts of the Radix Paeoniae Albas, 12.5 parts of Rhizoma Corydalis, 12.5 parts of Rhizoma Cyperis, 10.5 parts of the Radixs Linderae, 5.5 parts of the Rhizoma Atractylodis Macrocephalaes, 5.5 parts in Radix Glycyrrhizae, 5.5 parts of Myrrhas, 5.5 parts of Cortex Cinnamomis, 3.5 parts of Fructus Amomis and Radix Dipsacis.
In order to reach better therapeutic effect, described Rhizoma Corydalis, Rhizoma Cyperi and Myrrha are preferably Rhizoma Corydalis (processed with vinegar), Rhizoma Cyperi (processed with vinegar) and the Myrrha (processed with vinegar) through concocting; The described Rhizoma Atractylodis Macrocephalae is preferably the Rhizoma Atractylodis Macrocephalae (parched) through concocting.The concocting method of above-mentioned raw materials medicine can be carried out according to the disclosed method of " Chinese medicine voluminous dictionary " (Shanghai science tech publishing house).
Used each crude drug of the present invention all can be bought from common pharmacy and obtain, and its specification meets national medical standard.
The present invention is according to traditional theory of Chinese medical science, 12 flavor pure natural medicals such as Radix Bupleuri have been selected for use, process through extraction, natural Chinese medicinal herb has drug effect gentleness, conditioning functions is strong and toxic and side effects is low advantage, by the pharmaceutical composition that natural drug is formed, its overall therapeutic effect is more stable and lasting.
Prove that according to the pharmacological research data Chinese medicine composition of the present invention is except that protecting the liver, the antiinflammatory, analgesia, sedation, the animal uterus smooth muscle being had lax and suppresses the effect of its tension force and motion.The pharmacological research data of single medicinal material shows, Radix Bupleuri, Radix Paeoniae, Rhizoma Corydalis, Myrrha, Rhizoma Cyperi all have analgesia, sedation, wherein Radix Paeoniae, Rhizoma Cyperi, Radix Angelicae Sinensis have stronger spasmolysis to the animal smooth muscle, and these all are the pharmacodynamics bases that Chinese medicine composition of the present invention can be treated dysmenorrhea.
Medicine activity component of the present invention can add various adjuvants required when preparing different dosage form, for example disintegrating agent, lubricant, adhesive etc., method of Chinese medicinal with routine is prepared into any oral formulations commonly used, can be pill, capsule, tablet, powder, granule or oral liquid etc. for example, be preferably capsule.
Preferably, a kind of method for preparing Chinese medicine composition of the present invention may further comprise the steps:
(1) takes by weighing each crude drug by following weight: Radix Bupleuri 12-13 part, Radix Angelicae Sinensis 12-13 part, Radix Paeoniae Alba 12-13 part, Rhizoma Corydalis 12-13 part, Rhizoma Cyperi 12-13 part, Radix Linderae 10-11 part, Rhizoma Atractylodis Macrocephalae 5-6 part, Radix Glycyrrhizae 5-6 part, Myrrha 5-6 part, Cortex Cinnamomi 5-6 part, Fructus Amomi 3-4 part and Radix Dipsaci 4-5 part;
(2) above-mentioned 12 flavor crude drug are decocted with water, decoction liquor filters, and filtrate is concentrated into thick paste, adds microcrystalline Cellulose, mixing, and drying under reduced pressure is pulverized, and sieves, and mixing is granulated, promptly.
In the step (2), preferred, 12 flavor crude drug are added 8 times of weight water logging bubbles 2 hours, decoct again 3 times, decocted 2 hours at every turn;
In the step (2), preferably, filtrate is concentrated into the thick paste of relative density 1.20~1.24 (80~85 ℃);
In the step (2), the temperature of described drying under reduced pressure is 60 ℃.
Pharmacy before clinical, pharmacology, toxicological study, Chinese medicine composition preparation technology of the present invention is reasonable, steady quality, controlled.
Pharmacodynamics test proves that this medicine has very strong analgesic activity, and there are very strong inhibition and spasmolysis in the uterus, for the treatment dysmenorrhea provides strong pharmacological basis.
Chinese medicine composition of the present invention and YUEYUESHU have been carried out pharmacodynamics relatively, and the result shows that the analgesic effect of Chinese medicine composition 6g/kg of the present invention and YUEYUESHU 25g/kg is close, but dosage differs 4 times more than.Chinese medicine composition dosage 2% * 1ml energy all-out confrontation oxytocin of the present invention is to the excitation of rat uterus, the frequency, amplitude, energy of uterine activity all significantly reduced, P<0.01~0.001, and YUEYUESHU dosage 30% * 1ml only can reduce amplitude, P<0.05 in the excited uterus of oxytocin.Its active frequency, energy there is not the P of influence<0.05; So Chinese medicine composition of the present invention has possessed the characteristics that therapeutic effect is good, taking dose is little.
Chinese medicine composition acute toxicity test of the present invention shows, mouse gavaging Chinese medicine composition one twice-daily of the present invention, and total dose was 300g/kg on 1st, observing did not have deadly in 7 days, and maximum tolerated dose 300g/kg is 625 times of adult's dosage, illustrate that Chinese medicine composition toxicity of the present invention is very little, drug safety.
Chinese medicine composition of the present invention is a pure Chinese medicinal preparation, does not contain toxicity medical material and non-official remedy material in the prescription, can effectively treat primary dysmenorrhea.The clinical soreness of waist pain pain that is applicable to, fatigue and weakness, on the low side through measuring after advanced menstruation or the mistake, menses are purple dark or blood stasis piece etc. arranged.For menoxenia, chronic basin glue inflammation etc. all has significant curative effect.
Usage and consumption: the dosage of medicine of the present invention depends on concrete dosage form, and factor such as age of patient, body weight, health status.As guidance: capsule, oral at every turn (taking after mixing it with water) 3-6g (4) that is grown up, every day 2~3 (3) is inferior; Menstruation the last week continues to menstruation and ends in back 3 days, serve on 3 menstrual cycle.
The specific embodiment
Further describe the present invention by the following examples, it should be understood that these embodiment only are used for the purpose of illustration, never limit protection scope of the present invention.
The preparation of embodiment 1 capsule
Take by weighing each crude drug (unit: g): Radix Bupleuri 12, Radix Angelicae Sinensis 12, the Radix Paeoniae Alba 12, Rhizoma Corydalis (vinegar system) 12, Rhizoma Cyperi (vinegar system) 12, the Radix Linderae 10, the Rhizoma Atractylodis Macrocephalae (stir-fry) 5, Radix Glycyrrhizae 5, Myrrha (vinegar system) 5, Cortex Cinnamomi 5, Fructus Amomi 3, Radix Dipsaci 4 by following weight;
Above-mentioned 12 flavor crude drug add 8 times of weight water logging bubbles 2 hours, decoct 3 times, decoct 2 hours at every turn; Merge decoction liquor, filter, filtrate is concentrated into the thick paste of relative density 1.20~1.24 (80~85 ℃), and it is an amount of to add microcrystalline Cellulose, mixing, drying under reduced pressure (60 ℃) is pulverized, and sieves, and it is an amount of to add microcrystalline Cellulose again, sieves, add magnesium stearate, mixing is granulated, and is encapsulated, promptly.
The preparation of embodiment 2 granules
Take by weighing each crude drug (unit: g): Radix Bupleuri 13, Radix Angelicae Sinensis 13, the Radix Paeoniae Alba 13, Rhizoma Corydalis 13, Rhizoma Cyperi 13, the Radix Linderae 11, the Rhizoma Atractylodis Macrocephalae 6, Radix Glycyrrhizae 6, Myrrha 6, Cortex Cinnamomi 6, Fructus Amomi 4, Radix Dipsaci 5 by following weight;
Above-mentioned 12 flavor crude drug add 10 times of weight water logging bubbles 2 hours, decoct 2 times, decoct 2 hours at every turn; Merge decoction liquor, filter, filtrate is concentrated into the thick paste of relative density 1.20~1.24 (80~85 ℃), and it is an amount of to add microcrystalline Cellulose, mixing, drying under reduced pressure (60 ℃) is pulverized, and sieves, and it is an amount of to add microcrystalline Cellulose again, sieves, add magnesium stearate, mixing is granulated, promptly.
The preparation of embodiment 3 tablets
Take by weighing each crude drug (unit: g): Radix Bupleuri 12.5, Radix Angelicae Sinensis 12.5, the Radix Paeoniae Alba 12.5, Rhizoma Corydalis 12.5, Rhizoma Cyperi 12.5, the Radix Linderae 10.5, the Rhizoma Atractylodis Macrocephalae 5.5, Radix Glycyrrhizae 5.5, Myrrha 5.5, Cortex Cinnamomi 5.5, Fructus Amomi 3.5, Radix Dipsaci 4.5 by following weight;
Above-mentioned 12 flavor crude drug add 8 times of weight water logging bubbles 3 hours, decoct 3 times, decoct 2 hours at every turn; Merge decoction liquor, filter, filtrate is concentrated into the thick paste of relative density 1.20~1.24 (80~85 ℃), and it is an amount of to add microcrystalline Cellulose, mixing, drying under reduced pressure (60 ℃), pulverize, sieve, it is an amount of to add microcrystalline Cellulose again, sieves, and adds magnesium stearate, mixing is granulated, granulate, and tabletting, promptly.
The optimum preparation condition test of test example 1 Chinese medicine composition of the present invention
One, decocting part technology
(1) test 1: with the medical material Radix Angelicae Sinensis, Rhizoma Cyperi, Cortex Cinnamomi, Fructus Amomi that contain volatile oil in the Chinese medicine composition of the present invention totally four kinds extract volatile oil, gained volatile oil is mixed with all the other 8 herbal medicine water decoction extracts, must product 1 (volatile oil is with decoct);
Test 2: with 12 in the Chinese medicine composition of the present invention flavor crude drug all carry out decocting boil extract obtained, product 2 (water decoction).
Test 3:
To test 1 and test 2 resulting products 1 and 2 carry out drug effect, acute toxicity test relatively.The result shows, mice acetic acid is brought out writhing test, and both do not have significant difference (P>0.05); And product 1 toxicity strengthens, and 22 mices (total dose 300g/kg on the one) have 7 death, and none example of product 2 (total dose 300g/kg on the one) is dead.
(2) medicine 60% concentration of alcohol alcohol deposition method gained preparation of the present invention and product 2 (water decoction) are carried out drug effect, acute toxicity test relatively, both do not have significant difference (P>0.05) as a result.Though the extract obtained weight of alcohol deposition method only is water decoction 1/2,, adopt the water decoction extraction and preparation technique comparatively suitable from curative effect and cost consideration.
Among the preparation technology decocting is boiled number of times, time and amount of water and carry out positive quadraturing design test, the result decocts 3 times, and each 2 hours, amount of water was an optimum process condition for 8 times.The required ratio of adjuvant of capsule is also carried out positive quadraturing design test, and starch 40g, magnesium stearate 3g are best proportioning.
Test example 2 Chinese medicine compositions of the present invention and compare with the YUEYUESHU pharmacodynamics
One, Chinese medicine composition of the present invention and YUEYUESHU board TONGJINGBAO KELI single administration Dichlorodiphenyl Acetate bring out the mouse writhing experiment relatively:
Female 45 the 18~22g of mice divide equally 3 groups by body weight, 15 every group.Each group is gastric infusion respectively, blank (water) 30g/kg, confession reagent thing (Chinese medicine composition of the present invention, the capsule that embodiment 1 is prepared) 6g/kg, YUEYUESHU board TONGJINGBAO KELI (as if the western Pharmacy stock Co., Ltd in Henan produces) 25g/kg, irritated behind the stomach 1 hour, lumbar injection 0.6% acetic acid 0.2ml/ only, the observation mice was turned round the body number in 20 minutes, and experimental result sees Table 1
Table 1 brings out the analgesic activity of mouse writhing experiment for reagent thing and YUEYUESHU board TONGJINGBAO KELI single administration Dichlorodiphenyl Acetate
Group |
Dosage g/kg |
Number of animals (only) |
Take ip0.6% glacial acetic acid after 1 hour |
Turned round the body number of times in 20 minutes |
Suppression ratio (%) |
Contrast (water) |
30 |
15 |
40.80 |
|
YUEYUESHU |
25 |
15 |
17.00 |
58.33 |
For the reagent thing |
6 |
15 |
16.07 |
60.61 |
By above result as seen, compare with matched group (water) for reagent thing, YUEYUESHU board TONGJINGBAO KELI, by statistics the equal highly significant of both analgesic activities (P<0.001).And YUEYUESHU board TONGJINGBAO KELI 25g/kg and confession reagent thing 6g/kg effect close (P<0.05).But both compare by taking dose, and are littler 4 times more than than YUEYUESHU board TONGJINGBAO KELI dosage for the reagent thing.
Two, Chinese medicine composition of the present invention and YUEYUESHU board TONGJINGBAO KELI compare the influence of isolated uterine smooth muscle
Method: the same; rat is injected diethylstilbestrol in advance; but the uterus of taking off is put in the Rockwell liquid, makes the uterus inactive, traces one section normal activity after static 15 minutes and adds oxytocin 0.01u/ml0.04~0.08 again trace 30 minutes in 40ml Rockwell liquid.When selecting the oxytocin effect to reach the peak in 10 minutes, add Rockwell liquid 1ml respectively, supply reagent thing (Chinese medicine composition of the present invention, the capsule that embodiment 1 is prepared) 2% * 1ml, YUEYUESHU board TONGJINGBAO KELI 30% * 1ml relatively supplies the effect to oxytocin of reagent thing, YUEYUESHU board TONGJINGBAO KELI.
Table 2 is for the influence to uterine smooth muscle contraction frequency due to the oxytocin of reagent thing and YUEYUESHU board TONGJINGBAO KELI
Group |
The uterus number |
Give behind the oxytocin frequency time/10 minutes (X ± SD) |
Give the variation (X ± SD) of frequency behind Rockwell liquid or the medicine |
Preceding 10 gradation/10 minutes (± %) |
Back 10 gradation/10 minutes (± %) |
Rockwell liquid |
6 |
7.33±2.88 |
6.83±2.48 (+3.60±45.88) |
5.33±2.42 (-22.46±31.62) |
For reagent thing (2% * 1ml) |
7 |
9.14±0.90 |
4.92±2.21 (-54.13±22.33) |
2.29±2.06 (-75.83±21.52)※※ △△ |
YUEYUESHU (30% * 1ml) |
7 |
8.71±1.89 |
6.29±1.25 (-26.07±17.18) |
5.29±1.38 (-37.42±20.83) |
Annotate: 1, driving in the pipe is 40ml Rockwell liquid
2, with the matched group ratio
*P<0.05
*P<0.01
3, for reagent thing and YUEYUESHU board TONGJINGBAO KELI than △ P<0.05 △ △ P<0.01;
Table 3 is for the influence to uterine smooth muscle shrinkage amplitude due to the oxytocin of reagent thing and YUEYUESHU board TONGJINGBAO KELI
Group |
Uterus number (individual) |
Gave amplitude behind the oxytocin (X ± SDnm)/10 minute |
Variation (X ± SDnm/10 branch) to amplitude behind Rockwell liquid or the medicine |
Preceding 10 minutes nm/10 branches (± %) |
The 10 fens nm/10 branches in back (± %) |
Rockwell liquid |
6 |
36.41±20.30 |
47.51±24.07 (36.72±42.66) |
49.42±18.79 (46.98±33.86) |
For reagent thing (2% * 1ml) |
7 |
56.51±15.36 |
57.96±16.15 (+2.37±7.72) |
23.47±18.29△△△ (-59.16±29.09)*** |
YUEYUESHU (30% * 1ml) |
7 |
56.92±12.69 |
63.55±16.86 (+11.36±17.35) |
64.83±14.49 (+14.63±14.63)* |
Annotate: 1, with the matched group ratio
*P<0.05
* *P<0.001
2, for reagent thing and YUEYUESHU board TONGJINGBAO KELI than △ △ △ P<0.001
Table 4 is for the influence to uterine motility (frequency * amplitude) due to the oxytocin of reagent thing and YUEYUESHU board TONGJINGBAO KELI
Group |
Uterus number (individual) |
Give behind the oxytocin energy/10 minute (X ± SD) |
Give the variation (X ± SD) of energy behind Rockwell liquid or the medicine |
Energy/10 minute (± %) |
Energy/10 minute (± %) |
Rockwell liquid |
6 |
256.32±184.34 |
311.35±158.34 (+48.10±92.54) |
252.34±119.41 (+20.41±75.42) |
For reagent thing (2% * 1ml) |
7 |
516.57±137.66 |
242.71±139.85△ (-53.49±21.11) |
68.29±79.97△△△ (-87.72±13.58)** |
YUEYUESHU (30% * 1ml) |
7 |
504.71±181.95 |
404.58±156.66 (-16.69±29.26) |
349.85±142.79 (-26.98±31.53)* |
Annotate: 1, with the matched group ratio
*P<0.05
*P<0.01
2, for reagent thing and YUEYUESHU board TONGJINGBAO KELI than △ P<0.05 △ △ △ P<0.001; The result shows, (2% * 1ml) can resist the excitation in oxytocin uterus for the reagent thing, uterus frequency, amplitude, energy are reduced, the effect highly significant (P<0.01-0.001), and YUEYUESHU board TONGJINGBAO KELI (30% * 1ml) only can reduce the amplitude (P<0.05) in the excited uterus of oxytocin, and though frequency and energy are slightly reduced, add up not remarkable.For the reagent thing (2% * 1ml) with YUEYUESHU board TONGJINGBAO KELI (30% * 1ml) effect compare both differences very, highly significant (P<0.001).
Conclusion: close by above two analgesic activities that experiment showed, confession reagent thing 6g/kg and YUEYUESHU board TONGJINGBAO KELI 25g/kg, but littler more than 4 times for reagent thing taking dose than YUEYUESHU.For reagent thing 2% * 1ml can the all-out confrontation oxytocin to the excitation in uterus, make frequency, amplitude, energy significantly reduce (P<0.01-0.001); And YUEYUESHU board TONGJINGBAO KELI 30% * 1ml only can reduce amplitude P<0.05 in the excited uterus of oxytocin.Both compare by statistics difference very, highly significant P<0.001.