CN108143759B

CN108143759B - Pharmaceutical composition for relieving dysmenorrhea and preparation method thereof

Info

Publication number: CN108143759B
Application number: CN201810031636.0A
Authority: CN
Inventors: 洪宗国; 袁琳; 宋庭宁; 肖新才
Original assignee: South Central University for Nationalities
Current assignee: South Central Minzu University
Priority date: 2018-01-12
Filing date: 2018-01-12
Publication date: 2021-04-06
Anticipated expiration: 2038-01-12
Also published as: CN108143759A

Abstract

The invention belongs to the technical field of medicines, and particularly relates to a pharmaceutical composition for relieving dysmenorrhea and a preparation method thereof, wherein the pharmaceutical composition for relieving dysmenorrhea comprises capsaicin, vegetable oil and Chinese mugwort volatile oil; the mass ratio of the capsaicin to the vegetable oil to the Chinese mugwort volatile oil is 0.01-0.03: 7-9: 1-2. The invention provides a pharmaceutical composition for relieving dysmenorrhea, which can warm meridians, promote blood circulation, promote fever, relieve dysmenorrhea, has low dosage, quick response and no obvious adverse reaction, and a preparation method thereof.

Description

Pharmaceutical composition for relieving dysmenorrhea and preparation method thereof

Technical Field

The invention belongs to the technical field of medicines, particularly relates to a pharmaceutical composition and a preparation method thereof, and particularly relates to a pharmaceutical composition for relieving dysmenorrhea and a preparation method thereof.

Background

Chinese mugwort belongs to the order of Campanulales, and is a perennial herb of Compositae or slightly half-shrub, named as Qi Zhou (old name in Qi Chun county), one of the "Qi Chun Sibao" (Qi Zhu, Qi ai, Qi Snake and Qi Tortoise) in Qi Chun county of Hubei province, a special Chinese herbal medicine, and Chinese national geographical indication products, stems and leaves can be used as medicines. The Chinese mugwort contains 69 known compounds, the content of volatile oil, the content of total flavone, the combustion heat quantity and the like of the Chinese mugwort are obviously superior to that of the Chinese mugwort produced in other areas, and the oil yield of the Chinese mugwort (1.06%) of the volatile oil is twice of that of the Chinese mugwort (0.54%). The Chinese mugwort is bitter and pungent in flavor, is non-toxic and can be taken after washing and smoking. Has effects of regulating qi and blood, dispelling cold and dampness, regulating menstruation, preventing miscarriage, warming channels, stopping bleeding, clearing heat, relieving cough, and eliminating phlegm. It can be used for treating menoxenia, abdominal psychroalgia, fetal hemorrhage, threatened abortion, and infertility due to cold womb. Chinese mugwort compares with ordinary chinese mugwort medicinal effect better, as early as the Ming dynasty, the pharmalogist Li Shizhen adds to Chinese mugwort's promotion, and records in "compendium of materia Medica" say: since the generation of Bei ai which is called yang of Tang and Hai ai which is called yang of Si Ming, Qi Zhou is the prevailing herb, and the prescription is used, and the weight is increased in the day, it is called Qi ai. The mutual transmission of the other moxa-moxibustion wine jar can not be penetrated, and the moxa-moxibustion wine can be penetrated. According to the book Qi Zhou Zhi, the book Bai ai Qi Zhou, comes out. Chinese mugwort is named after its origin. Li Shizhen, the father Li said that Li wen was rather studied on Qi ai, and it is known that Qi ai produced in Shanyang, recorded in Cheng Wu Yang, and used in Cheng Wu to treat moxibustion diseases, with its effect not supplemented by Xiao Bu. "compendium of materia Medica": qi ai' Zhi Bai Bing. It can be decocted for stopping vomiting, bloody flux, and sores on the lower part, and can promote the secretion of blood and qi; generate muscle, and avoid wind-cold, so people can get children. It is decocted for no indication of wind, pounded into juice, used for stopping bleeding, killing ascarid, boiled in water and used in pill or powder. Metrorrhagia and metrostaxis, hemorrhoidal bleeding, skin ulcer, abdominal pain, and miscarriage prevention. … … for tinea "

The volatile oil of Chinese mugwort is extracted from Chinese mugwort by steam distillation (patent No. 01106404.8), and is the most effective component in folium Artemisiae Argyi. The smell is similar to that of wormwood, the fragrant smell is fresh and slightly pungent, the fragrant smell is very thick, the fragrance is slightly pungent, the volatilization speed is high, the fragrant. The main components are ethyl acetate, eucalyptol, hydrated camphene, camphor, 2-terpineol, carvone, thujone and isocupressional, and the two are the exclusive properties of the Chinese mugwort volatile oil. The Chinese mugwort volatile oil is anti-inflammatory essential oil with good body maintenance, is helpful for improving the vitality of the body, improving the discomfort state, dispelling cold and removing dampness, warming and activating qi and blood, and clearing and activating the channels and collaterals, and is the first choice for women.

Capsaicin ((trans) 8-methyl-N-vanillyl-6-nonenamide) is an active ingredient of capsicum, capsaicin and some compounds related to the capsaicin are called capsaicine, and the capsaicin is a secondary metabolite produced by capsicum and can diminish inflammation, relieve pain, treat muscular soreness and the like, and because the capsaicin generates burning sensation when contacting the body surface of a human body, the body can be promoted to generate heat and relieve cold in the uterus.

Dysmenorrhea is one of the most common gynecological symptoms, refers to lower abdominal pain and distention before and after menstruation or during menstruation, accompanied by soreness of waist or other discomfort, and seriously affects quality of life. The dysmenorrhea is divided into primary dysmenorrhea and secondary dysmenorrhea, wherein the primary dysmenorrhea refers to dysmenorrhea caused by genital organ anergy lesion; secondary dysmenorrhea refers to dysmenorrhea caused by pelvic organic diseases, such as endometriosis and adenomyosis. Primary dysmenorrhea is common in adolescence and usually occurs within 1-2 years after incipient wetness. The main symptom is lower abdominal pain accompanied by regular onset of menstrual cycle. Secondary dysmenorrhea is usually progressively aggravated due to intimal dislocation, as is the case with primary dysmenorrhea. The pain begins after menstruation, appears 12 hours before menstruation at the earliest time, and is most severe after 1 st day of menstruation and is relieved after 2-3 days. Pain is often spasmodic. It is generally not accompanied by abdominal muscle tension or rebound pain. It is accompanied by nausea, vomiting, diarrhea, dizziness, asthenia, etc., and in severe cases, it turns white and gives off cold sweat.

The traditional Chinese medicine considers that dysmenorrheal is caused by unsmooth discharge caused by cold wading during menstrual period, cold dampness invading uterus and menstrual blood stagnation. The "blood stasis" is the key to the occurrence of dysmenorrhea, and is caused by the generation of blood stasis both by the excess syndrome of congealing cold with blood stasis, qi stagnation and blood stasis and by the deficiency syndrome of kidney qi and deficiency of qi and blood, thereby causing dysmenorrhea. So called, unblocking causes no pain, and unblocking causes pain, so activating blood and resolving stasis, and dredging meridians are the main therapeutic principles. The western medicine is used for multiple drug treatment, analgesics are mostly used, but the treatment is temporary and permanent, drug dependence can be caused after long-term use, side effects can be generated, and long-term use is not recommended. In traditional Chinese medicine, more oral prescriptions and patent drugs can achieve the purpose of addressing both the symptoms and root causes, but the ingredients are complex, the effect is slow, the preparation method is complex, and the use is inconvenient.

Disclosure of Invention

In order to solve the technical problems in the background art, the invention provides the pharmaceutical composition for relieving dysmenorrhea, which can warm meridians, promote blood circulation, promote fever and relieve dysmenorrhea, and has the advantages of low dosage, quick response and no obvious adverse reaction, and the preparation method thereof.

In order to achieve the purpose, the invention adopts the following technical scheme:

a pharmaceutical composition for relieving dysmenorrhea, which is characterized in that: the pharmaceutical composition for relieving dysmenorrhea comprises capsaicin ((trans) 8-methyl-N-vanillyl-6-nonenamide), vegetable oil (preferably camellia oil or grape seed oil), and Chinese mugwort volatile oil;

the mass ratio of the capsaicin to the vegetable oil to the Chinese mugwort volatile oil is 0.01-0.03: 7-9: 1-2.

Preferably, the mass ratio of the capsaicin to the vegetable oil to the Chinese mugwort volatile oil is 0.01-0.02: 7-9: 1-2.

Preferably, the mass ratio of the capsaicin to the vegetable oil to the Chinese mugwort volatile oil is 0.012-0.018: 7-9: 1-2.

Preferably, the mass ratio of the capsaicin to the vegetable oil to the Chinese mugwort volatile oil is 0.015-0.018: 7-9: 1-2.

Preferably, the dosage form of the pharmaceutical composition for relieving dysmenorrhea is liniment, patch, spray or plastics.

A process for preparing a pharmaceutical composition for alleviating dysmenorrhea as described above, comprising: the method comprises the following steps:

1) selecting folium Artemisiae Argyi from folium Artemisiae Argyi of folium Artemisiae Argyi, and extracting volatile oil of folium Artemisiae Argyi;

2) mixing the Chinese mugwort volatile oil prepared in the step 1) with vegetable oil in proportion to obtain a mixture;

3) adding capsaicin into the mixture obtained in the step 2) according to a proportion, uniformly stirring, and dissolving with ultrasonic assistance until no precipitate exists to obtain a light yellow transparent liquid.

Preferably, the volatile oil of the Chinese mugwort extracted in the step 1) is a grass green or light yellow clear liquid; the Chinese mugwort volatile oil contains 1, 8-cineole component; the mass percentage content of the 1, 8-cineole in the Chinese mugwort volatile oil is not less than 15%.

The invention has the advantages that:

the invention provides a pharmaceutical composition for relieving dysmenorrhea and a preparation method thereof, the pharmaceutical composition comprises capsaicin, vegetable oil and Chinese mugwort volatile oil which are light yellow transparent liquid, wherein the vegetable oil is a solvent, the Chinese mugwort volatile oil has the effects of resisting bacteria, diminishing inflammation, warming channels, activating blood and relieving pain, and is a main active ingredient of the pharmaceutical composition, the capsaicin can promote fever and relieve cold in uterus, and the synergistic effect of the capsaicin and the Chinese mugwort volatile oil has better curative effect on cold congealing and blood stasis type dysmenorrhea. The pharmaceutical composition for relieving dysmenorrhea starts from internal causes, takes blood circulation activation and stasis removal and meridian dredging as main treatment principles, utilizes the Chinese mugwort volatile oil for activating blood circulation and stasis removal, warming and activating the channels and collaterals, and capsaicin for promoting body fever and relieving uterus cold, and treats dysmenorrhea by virtue of synergistic effect of the Chinese mugwort volatile oil and the capsaicin. The western medicine is used for multiple drug treatment, analgesics are mostly used, but the treatment is temporary and permanent, and the long-term use of the western medicine can cause drug dependence and side effect, so the long-term use of the western medicine is not recommended. In traditional Chinese medicine, more oral prescriptions and patent drugs can achieve the purpose of addressing both the symptoms and root causes, but the ingredients are complex, the effect is slow, the preparation method is complex, and the use is inconvenient. The pharmaceutical composition for relieving dysmenorrheal has simple components and simple and convenient preparation method, and the Chinese mugwort volatile oil is a health-care product, has the effects of clearing damp and dispelling cold, resisting bacteria and diminishing inflammation, relieving asthma, relieving cough, clearing phlegm, warming and activating qi and blood, clearing and activating the channels and collaterals, relieving pain, purifying and repairing skin, resisting aging, scraping therapy and the like, and is beneficial to organisms without harm. The medicinal composition can be a liniment, and the liniment is directly applied to corresponding acupuncture points for administration, and particularly has good curative effect on cold-congealing blood stasis type dysmenorrhea, strong pertinence, small dosage, quick response and good treatment effect.

Detailed Description

Firstly, extracting main active ingredient Chinese mugwort volatile oil, specifically: the volatile oil of Chinese mugwort is extracted from Chinese mugwort by steam distillation according to the method described in the invention content of Chinese patent 'simple extraction of Chinese mugwort oil' (patent No. ZL 01106404.8).

The extracted folium Artemisiae Argyi volatile oil has clear and transparent appearance, strong and pure fragrance, and contains 1, 8-cineole component; the content (mass percent) of the 1, 8-cineole in the Chinese mugwort volatile oil is not less than 15 percent. The extracted volatile oil of mugwort was used in examples 1-6 below.

The pharmaceutical composition of the invention can be liniment, patch, film coating agent or spray and other dosage forms suitable for skin exterior, when the liniment is selected, the liniment is composed of Chinese mugwort volatile oil, capsaicin and camellia oil, wherein the Chinese mugwort volatile oil is the main active ingredient accounting for 10 percent to 20 percent,to explore its compositional formulation, applicants made L9 (3)⁴) The amounts of the components were determined by orthogonal experiments, the experimental design is shown in table 1.

TABLE 1

The results of the gauge head design and evaluation indices are shown in tables 2 and 3. Evaluation criteria: the pharmaceutical composition is applied to different dysmenorrheal patients, and is graded by taking the heat sensation and the comfort as indexes, wherein the scores are 10 respectively, and finally the total score is added. The higher the fraction, the better the effect, and the average value is finally taken.

TABLE 2

The results of the orthogonality experiment are shown in table 3.

TABLE 3

As shown in Table 3, the optimal formula comprises 1.5g of Chinese mugwort volatile oil, 0.02g of capsaicin and 7.7g of camellia oil.

However, the liniment is smeared on the belly, the skin is sensitive, capsaicin has strong burning sensation and strong irritation to the skin, and in order to enable a human body to be easily accepted and have strong comfort, the applicant sets a series of capsaicin concentration gradients (20mg-10mg) to determine the optimal formula. Specific methods and results are shown in table 4 below. Wherein the amount of folium Artemisiae Argyi volatile oil is fixed at 1.5g, and the amount of oleum Camelliae Japonicae is fixed at 7.7 g.

TABLE 4

As shown in the table above, the dose of capsaicin is 20mg, which is irritant, and when the dose is reduced to 10mg, which is not hot, so that the range is narrowed, and repeated experiments show that the dose of capsaicin is preferably 15-18mg, which has strong hot feeling and no hot feeling, the effect is mild, and the human skin is easily accepted.

Therefore, the final formula of the liniment capable of relieving dysmenorrheal comprises 7-9g of camellia oil, 1-2g of Chinese mugwort volatile oil and 15-18mg of capsaicin.

The using method comprises the following steps: the liniment is applied by shaking before application, and is applied to acupoints related to dysmenorrhea, such as QIHAI, ZHONGJI, GUANYUAN, BALIAO and/or uterus, wherein the uterus is 4 inches below the navel and 3 inches laterally, and the liniment can be applied to the belly with hot water cup or bag to accelerate its action.

The action mechanism of the pharmaceutical composition of the invention is as follows:

the invention starts from internal causes, takes the functions of promoting blood circulation by removing blood stasis and dredging the channels and collaterals as the main treatment principle, utilizes the Chinese mugwort volatile oil to promote blood circulation by removing blood stasis, warm and activate the channels and collaterals, and capsaicin to promote the body to generate heat and relieve the cold in the uterus, and treats the dysmenorrhea by the synergistic effect of the Chinese mugwort volatile oil and the capsaicin. The pharmaceutical composition is directly smeared on corresponding acupuncture points for administration, and has strong pertinence, small dosage, quick response and good treatment effect. The main active ingredients of the invention are Chinese mugwort volatile oil and capsaicin, and the Chinese mugwort volatile oil has the functions of antibiosis, anti-inflammation, warming channels, activating blood and relieving pain. Capsaicin promotes fever, relieves cold in uterus, and relieves dysmenorrhea under the synergistic effect of the two. The camellia oil is used as a solvent, has the effects of moisturizing, moistening and diminishing inflammation, can relieve the phenomena of skin chapping and pruritus after being applied every day, can treat scalds, burns, tinea corporis, chronic eczema and other skin diseases, also has the effects of promoting blood circulation to remove blood stasis, can eliminate red and detumescence, and is beneficial to the body without side effects compared with chemical solvents.

Examples 1 to 6:

1. a pharmaceutical composition for relieving dysmenorrhea comprises folium Artemisiae Argyi volatile oil, capsaicin and oleum Camelliae Japonicae. Mixing folium Artemisiae Argyi volatile oil, oleum Camelliae Japonicae and capsaicin at a ratio of 1-2: 7-9: mixing at a mass ratio of 0.015-0.018, stirring, and dissolving with ultrasonic assistance until no precipitate is formed to obtain light yellow transparent liquid. The liquid is applied to uterus acupoint of dysmenorrhea patient in menstrual period, 3 times a day, pain is relieved, and dysmenorrhea days are shortened. The pharmaceutical composition can relieve dysmenorrhea.

2. A pharmaceutical composition for relieving dysmenorrhea comprises folium Artemisiae Argyi volatile oil, capsaicin and oleum Camelliae Japonicae. Mixing folium Artemisiae Argyi volatile oil, oleum Camelliae Japonicae and capsaicin at a ratio of 1-2: 7-9: 0.01-0.02, stirring uniformly, and dissolving with ultrasonic assistance until no precipitate is formed to obtain light yellow transparent liquid. The liquid is applied to uterus acupoint of dysmenorrhea patient in menstrual period, and the pain intensity is reduced 3 times a day. The pharmaceutical composition can relieve dysmenorrhea.

3. A pharmaceutical composition for relieving dysmenorrhea comprises folium Artemisiae Argyi volatile oil, capsaicin and oleum Camelliae Japonicae. Mixing folium Artemisiae Argyi volatile oil, oleum Camelliae Japonicae and capsaicin at a ratio of 1-2: 7-9: mixing at a mass ratio of 0.01-0.03, stirring, and dissolving with ultrasonic assist until no precipitate is formed to obtain light yellow transparent liquid. The liquid is applied to uterus acupoint of dysmenorrhea patient in menstrual period, and the pain intensity is reduced 3 times a day. The pharmaceutical composition can relieve dysmenorrhea.

4. A pharmaceutical composition for relieving dysmenorrhea comprises oleum Camelliae Japonicae as solvent, and optionally other vegetable oils. And extracting volatile oil of folium Artemisiae Argyi, mixing the volatile oil, grape seed oil and capsaicin at a ratio of 1-2: 7-9: mixing at a mass ratio of 0.015-0.018, stirring, and dissolving with ultrasonic assistance until no precipitate is formed to obtain light yellow transparent liquid. The liquid is applied to uterus acupoint of dysmenorrhea patient in menstrual period, 3 times a day, and pain symptom is relieved. The pharmaceutical composition can relieve dysmenorrhea.

5. A pharmaceutical composition for relieving dysmenorrhea is suitable for liniment and other dosage forms, and is prepared from volatile oil of folium Artemisiae Argyi, oleum Camelliae Japonicae, capsaicin, ethanol, and n-butane by mixing at a ratio of 1-2: 7-9: 0.015-0.018: 0.5: 0.5, stirring uniformly, dissolving with ultrasonic assistance to obtain yellowish transparent liquid, placing the prepared medicinal composition in a spray can, and making into spray, which is sprayed onto uterus acupoint of dysmenorrhea patients at menstrual period for 3 times a day to relieve pain. The spray prepared from the pharmaceutical composition can relieve dysmenorrhea.

6. The liniment has therapeutic effect on dysmenorrhea of mouse

The preparation method of the medicinal composition liniment comprises the following steps: mixing oleum Camelliae Japonicae 7.7g, folium Artemisiae Argyi volatile oil 1.5g and capsaicin 17mg, stirring well, dissolving with ultrasonic assistance until no precipitate exists, and making into light yellow transparent liquid as liniment.

1.1 animals and groups:

60 healthy adult SPF-grade ICR female non-pregnant mice are taken as study objects and are randomly divided into 6 groups according to the body weight, a blank control group, a model group, a positive medicine group, a low, medium and high dose group of liniment, and 10 mice in each group.

1.2 model of dysmenorrhea:

before the experiment, the abdominal skin of the mouse is depilated by using an electric pet hair clipper, and the stomach is drenched with diethylstilbestrol 2mg/kg from the 1 st day of the experiment to cause artificial estrus so as to improve the sensitivity of the uterus of the mouse to oxytocin once a day for 11 days continuously. After 1h of gavage diethylstilbestrol every day, the mice were placed in a cold water bath at 20 + -2 ℃ for 10min, once a day for 11 days continuously. After 1 hour of last administration, 0.5U/piece of oxytocin is injected into the abdominal cavity to prepare the model of dysmenorrheal caused by congealing cold and blood stasis.

1.3 administration method and dose:

blank control group: gavage equal volume normal saline; preparing a model by the model group according to a model preparation method;

a positive drug group: preparing a model according to a model preparation method, and performing intragastric administration for 4-6h every day from the 5d of the intragastric diethylstilbestrol, and then administering 0.06g/kg of ibuprofen granules. d5-11, once daily for 7 consecutive days;

administration group: preparing a model according to a model preparation method, starting from the 5 th day of gavage diethylstilbestrol, after 4-6h of gavage, smearing the liniment (the low, medium and high dosages are respectively 0.25ml/kg, 0.50ml/kg and 1.00ml/kg) near the belly acupuncture point of the mouse with hair removed, d5-11, once a day and continuously for 7 days. After the animals in the above groups were perfused with diethylstilbestrol for 1 hour at 12d, oxytocin was intraperitoneally injected at a rate of 0.5U/mouse, and the writhing reaction of the mice was observed within 30 min.

1.4 Experimental results:

the writhing response is taken as an index of pain, and the experimental result is as follows:

the experimental result shows that the number of writhing times of the low-dose group of the liniment is less than that of the model group of the liniment, the pain relieving effect is achieved, the pain relieving effect is stronger along with the increase of the dosage of the liniment, the writhing inhibition rate of the high-dose group of the liniment is up to 80.64%, and the effect is obvious. The analgesic effect is not much different from that of ibuprofen.

Claims

1. A pharmaceutical composition for relieving dysmenorrhea, which is characterized in that: the pharmaceutical composition for relieving dysmenorrhea is prepared from capsaicin, vegetable oil and Chinese mugwort volatile oil; the Chinese mugwort volatile oil is grass green or light yellow clear liquid; the Chinese mugwort volatile oil contains 1, 8-cineole; the mass percentage content of the 1, 8-cineole in the Chinese mugwort volatile oil is not lower than 15%; the mass ratio of the capsaicin to the vegetable oil to the Chinese mugwort volatile oil is 0.015-0.018: 7-9: 1-2.

2. A pharmaceutical composition for alleviating dysmenorrhea according to claim 1, wherein said composition comprises: the vegetable oil is camellia oil or grape seed oil or other vegetable oil.

3. A pharmaceutical composition for alleviating dysmenorrhea according to claim 2, wherein said composition comprises: the dosage form of the pharmaceutical composition for relieving dysmenorrhea is liniment, patch, spray or plastics.

4. A process for the preparation of a pharmaceutical composition for relief of dysmenorrhea as defined in any one of claims 1 to 2 wherein: the method comprises the following steps: