A kind of Chinese medicine composition with analgesic effect and preparation method thereof
Technical field
The present invention relates to a kind of the have Chinese medicine composition of analgesic effect and the preparation method of said composition, particularly a kind of Chinese medicine composition for the treatment of the cancer pain and preparation method thereof, belong to the field of Chinese medicines.
Background technology
Cancer pain refers to the pain due to cancer, cancer related pathologies and anticancer therapy, is often chronic pain, is the common symptom of cancer patient.IASP (IASP) to the definition of pain is: impression during pain on a kind of undesirable sensation and emotion is accompanied by existing or potential tissue injury.Pain is often subjective, and everyone has just learned to express the vocabulary of pain in the getting up early of life by the experience of damage.Be that pain is often a kind of subjective feeling, be subject to the impact of environment and emotion, and be not only a kind of simple physiologic response.World's pain conference in 2002 gives the theory that pain is new, thinks that pain is a kind of disease, and is not only a kind of symptom; Pain has been listed in the fifth-largest vital sign of human body; All pain is all pernicious, never has optimum pain; Drug therapy is topmost part in pain therapy; Targeting, dose-effect relationship are linear to following pain therapy medicine more, action time is more lasting.
Cancer accounts for first of the current world population cause of the death.The middles and advanced stage that belong to while going to a doctor due to cancer patient, therefore, pain becomes a common sympton, directly affects patient's quality of life more.According to estimates, the existing cancer patient in the whole world approximately 1,400 ten thousand, wherein 30%~60% with pain in various degree, and most patients with advanced cancer are just experiencing the torment of cancer pain, and the nearly half patient does not obtain satisfied alleviation.The existing cancer patient of China approximately 2,000,000, pain incidence rate 40%~50%, wherein 25% patient does not obtain medical treatment, in, severe pain accounts for 20%.Therefore, control cancerous pain and be put into one of 4 emphasis of World Health Organization's cancer Comprehensive Control planning.Therefore, the alleviation cancerous pain is very necessary.
Cancerous pain is the pain that the cancer patient produces under various harmful factors stimulate, and makes the patient very painful, affects carrying out smoothly of effective antitumor plan.Due to aggravation and the intense stimulus of pain, directly affect patient's appetite, sleep, psychologic status and therapeutic effect, and having a strong impact on patient's life quality, be that the cancer patient loses treatment confidence and one of the major reason of desire of surviving.Cancer pain is as the common sympton of tumor, and its cause of disease directly and Tumor-assaciated.On treatment pain, Chinese and western medicine is fully different, and thinking is different.Doctor trained in Western medicine is all generally the neural pain relieving of anesthesia, the local anesthesia of pain is got up, allow the imperceptible pain of patient, in fact pain also exists, and has just anaesthetized nerve, has alleviated misery, alleviated symptom, the state of an illness also, in development, does not play any therapeutic effect, and excessive anesthetics has caused destruction to gastrointestinal function and hepatic and renal function.
Chinese medicine is obtaining significant progress aspect the treatment of cancer pain.Cancerous pain is very common in tumor patient, and the reason of its generation has multiple, as tumor is directly invaded or pressuring nerve; The tumor ramp is increased the peplos tension force of organ; The compressing of tumor makes the histoorgan ischemic necrosis; Tumor is broken or the impact of ulcer and some psychological factor etc.Control pain, can strengthen the confidence of patient to successive treatment timely and effectively, for essential condition is created in the treatment of protopathy.For late tumor patient, control pain can make its life quality be improved.For this reason, the treatment of control cancerous pain is listed in the emphasis planning of World Health Organization (WHO).Motherland's medical science is thought, although tumor is local patholoic change, yet, " strong people is without long-pending, and empty people has it ", the internal organs weakness, stagnation of QI-blood is the important pathologic basis of cancer.Qi depression to blood stasis, venation is obstructed, and stagnation of QI and blood may bring about pain, therefore to the suitable vital energy regualting and blood circulation-promoting of the treatment of cancerous pain, removing obstruction in the collateral to relieve pain.This Chinese medicine composition forms Chinese medicine compound by Rhizoma Corydalis, Radix Paeoniae Rubra, Rhizoma Cyperi, Herba Asari, Venenum Bufonis, the Rhizoma Pinelliae, Fructus Xanthii, Radix Glycyrrhizae etc., has the effect of promoting flow of QI and blood, promoting the flow of QI in the collateral by warming the meridian, heat-clearing and toxic substances removing, the refreshment of having one's ideas straightened out.The theory that meets the Chinese traditional treatment cancer, be applicable to spend the patient among cancerous pain.
Summary of the invention
One object of the present invention is to provide a kind of effect with promoting flow of QI and blood, removing obstruction in the collateral to relieve pain, and light, the moderate cancerous pain caused for pulmonary carcinoma, gastric cancer, hepatocarcinoma etc. belongs to the Chinese medicine composition of syndrome of qi stagnation and blood stasis;
Another object of the present invention is to provide the preparation method of above-mentioned Chinese medicine composition.
The object of the present invention is achieved like this, according to the Chinese medicine and pharmacy theory, utilizes the property of medicine of medical herbs uniqueness, adopts Rhizoma Corydalis, Radix Paeoniae Rubra, Rhizoma Cyperi, Herba Asari, Venenum Bufonis, the Rhizoma Pinelliae, Fructus Xanthii, Radix Glycyrrhizae according to certain compatibility requirement, through special process, processes.
Crude drug composition and the proportioning of preparation Chinese medicine composition of the present invention are as follows:
Rhizoma Corydalis 400~600g, Radix Paeoniae Rubra 400~600g, Rhizoma Cyperi 200~400g, Herba Asari 200~400g, Venenum Bufonis 3~7g, the Rhizoma Pinelliae 100~200g, Fructus Xanthii 200~400g, Radix Glycyrrhizae 100~200g.
The crude drug of Chinese medicine composition of the present invention forms best proportioning for (by weight):
Rhizoma Corydalis 500g, Radix Paeoniae Rubra 500g, Rhizoma Cyperi 300g, Herba Asari 300g, Venenum Bufonis 5g, Rhizoma Pinelliae 150g, Fructus Xanthii 300g, Radix Glycyrrhizae 150g.
Medicine of the present invention can be in the middle of following dosage form granule, tablet, capsule, pill a kind of.
Medicine of the present invention can adopt the preparation of following method: gets Rhizoma Cyperi, Herba Asari, Fructus Xanthii and adds 4~8 times of water gagings, add thermal distillation 3~5 hours, collect volatile oil, add 2~4 times of amount betacyclodextrins and grind 2 hours, and drying, standby, the another device of the aqueous solution after distillation is collected; Medicinal residues and Rhizoma Corydalis, Radix Paeoniae Rubra, the Rhizoma Pinelliae, Radix Glycyrrhizae merge, and add 6~10 times of water gagings and decoct 1~3 time, each 1~3 hour, collecting decoction and above-mentioned distillation rear solution, filter, being evaporated to 60 ℃ of mensuration relative densities is 1.05~1.10, adds ethanol and makes to reach 50~70% containing the alcohol amount, standing, filter, filtrate recycling ethanol, continuing to be concentrated into 60 ℃ of mensuration relative densities is 1.25~1.35, drying under reduced pressure, standby; Above-mentioned two dry things are mixed, pulverize, add the Venenum Bufonis fine powder, fully mix homogeneously, add the conventional adjuvant of pharmaceutics, makes required dosage form, obtains.
The preparation technology of medicine of the present invention can be: gets Rhizoma Cyperi, Herba Asari, Fructus Xanthii and adds 6 times of water gagings, add thermal distillation 4 hours, collect volatile oil, add 3 times of amount betacyclodextrins and grind 2 hours, and drying, standby, the another device of the aqueous solution after distillation is collected; Medicinal residues and Rhizoma Corydalis, Radix Paeoniae Rubra, Radix Glycyrrhizae merge, and add 8 times of water gagings and decoct 2 times, each 2 hours, collecting decoction and above-mentioned distillation rear solution, filter, being evaporated to 60 ℃ of mensuration relative densities is 1.05~1.10, adds ethanol and makes to reach 60% containing the alcohol amount, standing, filter, filtrate recycling ethanol, continuing to be concentrated into 60 ℃ of mensuration relative densities is 1.25~1.35, drying under reduced pressure, standby; Above-mentioned two dry things are mixed, pulverize, add the Venenum Bufonis fine powder, fully mix homogeneously, add the conventional adjuvant of pharmaceutics, makes required dosage form, obtains.
The application of light, the moderate cancerous pain that Chinese medicine composition of the present invention mainly causes in treatment pulmonary carcinoma, gastric cancer, hepatocarcinoma etc. in belonging to syndrome of qi stagnation and blood stasis.
Following experimental example, by light, the curative effect that the moderate cancerous pain belongs to syndrome of qi stagnation and blood stasis of observing that this traditional Chinese medicine composition for treating pulmonary carcinoma, gastric cancer, hepatocarcinoma etc. cause, further illustrates the medical application of medicine of the present invention.
Use potentiation in order to understand its prescription 5, this research adopts animal Blood stasis test model, observes the impact of Chinese medicine composition of the present invention on the animal pharmacology effect.
The impact of a pair of mice analgesic activity of experimental example
Experimental animal: the white mice of Kunming kind, body weight 18~22 grams, male and female dual-purpose.
Writhing method: utilize the acetic acid induced pain, make mice produce writhing response, the analgesic activity of checking this product.Get 40 of Kunming mouses, be divided at random 4 groups, every group 10, the water matched group, this product Chinese medicine composition group low dose, middle dosage, heavy dose of gastric infusion respectively, administration is after 30 minutes, lumbar injection 5% acetum (0.2mg/20g), observe 10 minutes endogenous cause of ill pain of every mice and cause time and the number of times of writhing, the results are shown in Table 1.
The analgesic activity (writhing method) of table 1 this product to mice
Annotate: with the water matched group, compare: * P<0.05.
Above-mentioned test data shows, each dosage group writhing of this product obviously extends incubation period, and administration is respectively organized the writhing number of times and obviously is less than the prompting of water matched group result of the test: this product analgesic activity is obvious, and the therapeutic effect of the medicine of two kinds of preparation method systems is close.
Experimental example two present compositions are on the hemorheological impact of rat experiment Blood stasis
1, given the test agent: medicine group of the present invention; Radix Salviae Miltiorrhizae Injection (1.5g/ml); Adrenalin hydrochloride injection (1mg/ml), heparin sodium powder (150,000 units/gram); Sodium citrate.
2, instrument: rotation cartridge type Blood rheology measurement, erythrocyte electrophoresis instrument, platelet adhesion instrument.
3, animal: SD kind rat, male and female half and half, body weight (300 ± 30) g.
4, test method and result
By weigh labelling be divided at random 4 groups of 40 rats, 10 every group, be respectively: blank group (20ml/kgd tap water); Blood stasis model group (20ml/kgd); Radix Salviae Miltiorrhizae positive controls (2.8g/kgd); This Chinese medicine composition group (6.0g crude drug/kgd), except blank and model group, all ig administrations in continuous 7 days.Except the blank group, all the other each groups all copy the Blood stasis model.
Model copy: in the 7th day, sc adrenalin hydrochloride 8ug/kg2 time, midfeather 4 hours, between double injection, immerse rat in frozen water 5 minutes, after disposal, stops eating.In the 8th day, with urethane (20%) intraperitoneal anesthesia (3ml/kg), the carotid artery intubate was got blood 4.2ml, and wherein 3ml injects anticoagulant heparin pipe (concentration 1.39 * 10
-2mmol/L blood), 1.2ml Induced By Na-citrate Injection Into anticoagulant tube (concentration 3.8%, test tube is silication in advance).
Heparin anti-coagulating is used for measuring:
1. the high viscosity (η that cuts of whole blood
hmPas), the low viscosity (η that cuts of whole blood
lmPas): rotating cylinder viscometer is measured, high shear rate 200s
-1, low shear rate 40s
-1.
2. erythrocyte electrophoretic time (EPSs): self blood plasma dilution, erythrocyte electrophoresis instrument are measured, and under the microscope that the chessboard scale is housed, survey erythrocyte and come and go to the left and right two lattice required times, are erythrocyte electrophoretic time.
The sodium citrate anticoagulation is used for measuring platelet adhesion rate (glass bead method): anticoagulation 1ml is placed in 5ml long-neck ball vial, be placed on the platelet adhesion instrument, to take off after 5rpm rotating speed rotation 15min, before and after rotating, anticoagulation adds platelet diluent (1% ammonium acetate solution), measure and adhere to front and back, platelet count, calculate adhesion rate (PT).
Result: this Chinese medicine composition affects experimental result in Table 2 to hemorheologic parameters.
The impact (x ± s) of table 2 compositions on hemorheologic parameters
Annotate: model group and normal group compare:
*p<0.05; Medication group and model group compare:
△p<0.05.
Result of the test shows: this Chinese medicine composition can significantly reduce the high shear viscosity of whole blood, the low shear viscosity of whole blood; Significantly reduce platelet adhesion rate, shorten electrophoresis time.Play obvious function of promoting blood circulation to disperse blood clots.
The specific embodiment
Below with specific embodiment, illustrate again, but following embodiment only for being described, does not limit the present invention in the present invention.
Embodiment 1:
Prescription: Rhizoma Corydalis 400g, Radix Paeoniae Rubra 400g, Rhizoma Cyperi 200g, Herba Asari 200g, Venenum Bufonis 3g, Rhizoma Pinelliae 100g, Fructus Xanthii 200g, Radix Glycyrrhizae 100g.
Method for making: get Rhizoma Cyperi, Herba Asari, Fructus Xanthii and add 6 times of water gagings, add thermal distillation 4 hours, collect volatile oil, add 3 times of amount betacyclodextrins and grind 2 hours, drying, standby, the another device of the aqueous solution after distillation is collected; Medicinal residues and Rhizoma Corydalis, Radix Paeoniae Rubra, Radix Glycyrrhizae merge, and add 8 times of water gagings and decoct 2 times, each 2 hours, collecting decoction and above-mentioned distillation rear solution, filter, being evaporated to 60 ℃ of mensuration relative densities is 1.05~1.10, adds ethanol and makes to reach 60% containing the alcohol amount, standing, filter, filtrate recycling ethanol, continuing to be concentrated into 60 ℃ of mensuration relative densities is 1.25~1.35, drying under reduced pressure, standby; Above-mentioned two dry things are mixed, pulverize, add the Venenum Bufonis fine powder, fully mix homogeneously, get 1 part of mixing fine powders, 4 parts of sucrose, and 2.5 parts, dextrin, mix, and granulates, and 60~70 ℃ of dryings, make 1000g.
Embodiment 2:
Prescription: Rhizoma Corydalis 500g, Radix Paeoniae Rubra 500g, Rhizoma Cyperi 300g, Herba Asari 300g, Venenum Bufonis 5g, Rhizoma Pinelliae 150g, Fructus Xanthii 300g, Radix Glycyrrhizae 150g.
Method for making: get Rhizoma Cyperi, Herba Asari, Fructus Xanthii and add 8 times of water gagings, add thermal distillation 3 hours, collect volatile oil, add 4 times of amount betacyclodextrins and grind 2 hours, drying, standby, the another device of the aqueous solution after distillation is collected; Medicinal residues and Rhizoma Corydalis, Radix Paeoniae Rubra, Radix Glycyrrhizae merge, and add 6 times of water gagings and decoct 3 times, each 1 hour, collecting decoction and above-mentioned distillation rear solution, filter, being evaporated to 60 ℃ of mensuration relative densities is 1.05~1.10, adds ethanol and makes to reach 50% containing the alcohol amount, standing, filter, filtrate recycling ethanol, continuing to be concentrated into 60 ℃ of mensuration relative densities is 1.25~1.35, drying under reduced pressure, standby; Above-mentioned two dry things are mixed, pulverize, add the Venenum Bufonis fine powder, fully mix homogeneously, add starch to 360g, and mix homogeneously, make 1000 of capsules.
Embodiment 3:
Prescription: Rhizoma Corydalis 600g, Radix Paeoniae Rubra 600g, Rhizoma Cyperi 400g, Herba Asari 400g, Venenum Bufonis 7g, Rhizoma Pinelliae 200g, Fructus Xanthii 400g, Radix Glycyrrhizae 200g.
Method for making: get Rhizoma Cyperi, Herba Asari, Fructus Xanthii and add 4 times of water gagings, add thermal distillation 5 hours, collect volatile oil, add 2 times of amount betacyclodextrins and grind 2 hours, drying, standby, the another device of the aqueous solution after distillation is collected; Medicinal residues and Rhizoma Corydalis, Radix Paeoniae Rubra, Radix Glycyrrhizae merge, and add 10 times of water gagings and decoct 1 time, each 3 hours, collecting decoction and above-mentioned distillation rear solution, filter, being evaporated to 60 ℃ of mensuration relative densities is 1.05~1.10, adds ethanol and makes to reach 70% containing the alcohol amount, standing, filter, filtrate recycling ethanol, continuing to be concentrated into 60 ℃ of mensuration relative densities is 1.25~1.35, drying under reduced pressure, standby; Above-mentioned two dry things are mixed, pulverize, add the Venenum Bufonis fine powder, fully mix homogeneously, add microcrystalline Cellulose appropriate, adds starch to 450g, mix homogeneously, and granulation, be pressed into 1000, tablet, and film coating, obtain.
Embodiment 4:
Prescription: Rhizoma Corydalis 600g, Radix Paeoniae Rubra 600g, Rhizoma Cyperi 400g, Herba Asari 400g, Venenum Bufonis 7g, Rhizoma Pinelliae 200g, Fructus Xanthii 400g, Radix Glycyrrhizae 200g.
Method for making: get Rhizoma Cyperi, Herba Asari, Fructus Xanthii and add 6 times of water gagings, add thermal distillation 4 hours, collect volatile oil, add 3 times of amount betacyclodextrins and grind 2 hours, drying, standby, the another device of the aqueous solution after distillation is collected; Medicinal residues and Rhizoma Corydalis, Radix Paeoniae Rubra, Radix Glycyrrhizae merge, and add 6 times of water gagings and decoct 2 times, each 2 hours, collecting decoction and above-mentioned distillation rear solution, filter, being evaporated to 60 ℃ of mensuration relative densities is 1.05~1.10, adds ethanol and makes to reach 70% containing the alcohol amount, standing, filter, filtrate recycling ethanol, continuing to be concentrated into 60 ℃ of mensuration relative densities is 1.25~1.35, drying under reduced pressure, standby; Above-mentioned two dry things are mixed, pulverize, add the Venenum Bufonis fine powder, abundant mix homogeneously, add carboxymethylstach sodium and microcrystalline Cellulose is appropriate, mixes, and take water as binding agent, and the pill bar, be pressed into ball, obtains.
Embodiment 5:
Get the made capsule of embodiment 2 and treat 50 routine cancer pain patients (wherein pulmonary carcinoma 18 examples, hepatocarcinoma 20 examples, gastric cancer 12 examples).Therapeutic scheme: oral, one time 3, three times on the one.The rear observation of taking medicine, pain alleviates obvious 29 examples, produce effects 15 examples, invalid 6 examples, total effective rate reaches 88%.