CN101209285A

CN101209285A - Preparation and application of 'dingguiyou' soft capsule

Info

Publication number: CN101209285A
Application number: CNA2006100226817A
Authority: CN
Inventors: 牛锐
Original assignee: Individual
Current assignee: Individual
Priority date: 2006-12-28
Filing date: 2006-12-28
Publication date: 2008-07-02

Abstract

The invention relates to a prescription which is mainly composed of clove and cinnamon, the indication of the prescription is irritable bowel syndrome, and the effective part of clove and cinnamon is volatile oil which is determined by screening of pharmacodynamics. The soft capsules which are prepared by the volatile oil have elegant appearance, convenient administration and stable quality; proved by pharmacodynamic tests, the soft capsules can meet the requirements of the clinical medication of irritable bowel syndrome.

Description

A kind of fourth cassia oil soft capsule preparation method and purposes

Technical field

Pharmaceutical technology

Background technology

Flos Caryophylli, Cortex Cinnamomi are the Chinese medicine materials, and by prescription or be used for the treatment of stomachache separately and be the various gastropathy of cardinal symptom.Soft capsule is a kind of common formulations, is used for fat-soluble medicine more.

The active ingredient of Flos Caryophylli, cinnamomic treatment stomachache is a volatile oil, the tradition usage is to add in decoction or the powder to use, but the volatile oil content that decoction keeps is low, though and powder can keep whole volatile oil, but the dosage form backwardness is taken inconvenience and dosage is big, by suitable technology extraction effective ingredient volatile oil wherein, and make efficiently, dosage form easily, the treatment that is used for irritable bowel syndrome is the problem that the present invention solves.

Summary of the invention

With Flos Caryophylli, Cortex Cinnamomi is the main prescription that cures mainly irritable bowel syndrome of forming, and by the pharmacodynamics screening, determines that Flos Caryophylli, cinnamomic effective site are volatile oil.Through extracting, making with extra care, obtain effective site (fourth osmanthus volatile oil), and make wherein effective ingredient eugenol, cinnamic aldehyde content sum surpass 50% (eugenol of test agent, cinnamic aldehyde content sum reach about 83% in three batches).Because fourth osmanthus volatile oil has acid, effumability, to characteristics such as photaesthesia, therefore select for use soft capsule that volatile oil is wrapped in the soft capsule, volatile oil is hedged off from the outer world, covered the discomfort of medicine and smelt flavor, improve stability of formulation, the soft capsule that makes is exquisite appearance not only, taking convenience, steady quality, and medicament contg is accurate, the precision height, it is fast to prove effective, the bioavailability height.Prove through pharmacodynamics test: fourth cassia oil soft capsule has obvious facilitation (p＜0.05--0.01) to the small intestine movement of mice ahead running; The mouse small intestine motion that neostigmine is caused is hyperfunction obvious suppression effect (p＜0.05); Each dosage group suppresses that to the mouse small intestine motion that atropine causes certain antagonism is all arranged, and wherein act as excellent (p＜0.01) with 0.68g (crude drug in whole)/Kg dosage group; Fourth cassia oil soft capsule is not obvious to normal mouse gastric emptying motion effects, and the mice gastric emptying motion that 1.35g (crude drug in whole)/Kg dosage group causes neostigmine is hyperfunction obvious suppression effect (p＜0.05); 1.35,0.68, the mice gastric emptying motion that atropine is caused of 0.23g (crude drug in whole)/Kg dosage group suppresses that tangible antagonism is all arranged (p＜0.05-0.01), prompting this product has the effect of certain adjusting gastrointestinal motility.Dichlorodiphenyl Acetate induced mice pain reaction has significant analgesic activity (p＜0.001); The hot plate method experimental result shows, 60,90 and the 120min mice threshold of pain improve percentage rate all more than 50%, percentage rate is improved also more than 50% in the 90min mice threshold of pain, demonstrates good analgesic activity.As seen fourth cassia oil soft capsule has the active constituent content height, and pharmacological action is obvious, and is rapid-action, and characteristics such as bioavailability height can satisfy the requirement of clinical application.

Safety research: fourth cassia oil general pharmacology is learned research overview: large, medium and small three dosage of fourth cassia oil (4.05,1.35,0.45g crude drug in whole/kg), Beagle dog oral administration under the waking state, intubate gastric infusion under domesticated dog anesthesia (pentobarbital sodium i.v30mg/kg) state, after the administration 30,60,90,120,180, blood pressure (SBP, DBP, BP), respiratory frequency and the amplitude measured of 240min, body temperature, heart rate, electrocardiogram (P, QRS, ST, T ripple interval, amplitude) parameter, with average specific before the medicine than no significant difference.Large, medium and small three the dosage groups of fourth cassia oil (12.15,4.05,1.35g crude drug in whole/kg), press the administration of 0.2ml/10g body weight mouse stomach, 60min behind the medicine, to mouse peritoneal injection 45mg/kg pentobarbital sodium, the length of one's sleep of animal and normal saline matched group be no difference of science of statistics (P＞0.05) relatively all; Mouse peritoneal injection 25mg/kg sleeping each dosage group of number of pentobarbital sodium animal and matched group are compared no difference of science of statistics (P＞0.05); To spontaneous activity number of times in the mice 10 minutes, each dosage group and matched group be P＞0.05 relatively.In sum: the above-mentioned dosage of fourth cassia oil does not have influence to dog blood pressure, breathing, body temperature, electrocardiogram; Sleeping each time for falling asleep of number of pentobarbital sodium mice does not have influence; To mice autonomic activities unrestraint effect.Fourth cassia oil studies on acute toxicity overview: fourth cassia oil prerun 4.0ml/kg is LDm, sample dilutes by 1: 0.8 ratio diminishing method between group with soybean oil, 80 of mices, male and female half and half, be divided into 8 groups, the 8th group is the soybean oil matched group, accelerated breathing, lazy moving, drowsiness appears in animal after the administration of the heavy dose of group of part, animal begins death behind the administration 15min, dead animal after about 8 hours full recovery normal, animal dead time, quantity and symptom performance occur and reduces with dosage and prolong, reduce and alleviate, the reaction of salad oil treated animal no abnormality seen.Press the Bliss method and calculate LD ₅₀Be 2.3200 ± 0.1596ml/kg (1.99～2.72ml/kg), be equivalent to 48.33 ± 3.325g crude drug in whole/kg (41.46～56.67g crude drug in whole/kg).Fourth cassia oil long term toxicity research overview: continuous 100 days of fourth cassia oil irritate the stomach rat (1.05,3.15, the three dosage groups of 9.45g crude drug in whole/Kg), matched group is given soybean oil, and drug withdrawal convalescent period observed 21 days.Successive administration 100 days, the outward appearance sign of three dosage group rats, behavioral activity Non Apparent Abnormality.The feedstuff day consumption increases with body weight, increases and the prolongation of time tends towards stability or reduces with body weight, and each treated animal does not have significant difference to feed consumption.Body weight gain increases with the drug dose size, (0 day) ratio before administration 100 days and the administration, weight average increases: heavy dose of 156.76g, middle dosage 164.0g, low dose of 182.92g, matched group 176.52g, heavy dose of group relatively has significant difference (P＜0.05) with matched group.Relatively all no difference of science of statistics of index and 10 indexs of blood biochemistry checking and matched group are checked in administration 100 days, large, medium and small dosage group peripheral hemogram.Drug withdrawal was observed 21 days, and peripheral hemogram is checked the index blood biochemistry checking, and data fluctuateed in normal range, compared P＞0.05 with matched group.The heavy dose of treated animal of anatomic observation removes has the individual animal liver to increase to some extent, liver coefficient and matched group be P＜0.05 relatively, lung tissue has naked eyes as seen outer unusually, other is organized does not all have the visible pathological changes of naked eyes, drug withdrawal recovers to observe 21 days, and each group of perusal is consistent, and heavy dose of liver coefficient and matched group be P＞0.05 relatively, show that drug withdrawal can recover normally more equal no difference of science of statistics between other each organ coefficient group; Tissue pathology checking, the heart, liver, spleen, lung, kidney, brain, cerebellum, testis, epididymis, prostate, uterus, ovary, thyroid, thymus, stomach, adrenal gland, duodenum, pancreas, return, colon, breastbone myeloid tissue, 100 days heavy dose of group part animal liver leaflet structures of administration are owed clearly, the slight hepatic cell edema, 21 days no abnormality seens are observed in drug withdrawal, and other respectively organizes each internal organs no abnormality seen.To sum up: the heavy dose of group of prompting has the mild damage to the hepatic tissue of rat, and drug withdrawal is observed and can be recovered normal in 21 days, and other each dosage treated animal no abnormality seen shows that it is safe that the following dosage rat of 9.45g crude drug in whole/Kg is taken for a long time.The fourth cassia oil is in crude drug in whole 4.05,1.35, three dosage of 0.45g/kg, observes 21 days through continuous 100 days oral administrations of Beagle dog and drug withdrawal convalescent period.Each dosage treated animal there is no unusually after the administration.Body weight gain, each organize 100 days body weight of administration than administration before for the second time, balanced growth is, heavy dose of group 2.7gkg, middle dosage group 2.57kg, small dose group 3.15kg, matched group 2.52kg, more equal no difference of science of statistics between group shows the weight of animals is increased obviously influence of nothing.Animal appearance is normal, active, a quilt hair gloss, eye, nose ear, mouth, the no abnormal secretions in the natural hole of genitals, and defecation color shape is all normal.Drug withdrawal recovered 21 days, and each treated animal there is no unusually.Preceding 2 times of medicine, administration 50,100 days and drug withdrawal were observed 21 days, each index between each group of peripheral hemogram inspection all fluctuates in normal range, 24 animals of administration bone marrow examination in 100 days, drug withdrawal is observed and was checked 8 animals in 21 days, grain system, red system, pouring system, platelet etc. there is no abnormal cell, and no difference of science of statistics is compared in the myelogram active proliferation between each data set.Biochemical 10 the index inspections of blood, index there is no unusually, and Electrocardioscopy is sinus rhythm, and P, QRS ripple etc. are consistent with main ripple direction, and each wave voltage, time are normal.System's each main organs of each treated animal that becomes celestial, no naked eyes are as seen unusual; Organ coefficient is learned processing by statistics, and 100 days anatomic observations of administration all do not have the visible pathological changes of naked eyes, and each organizes organ coefficient and matched group than P＞0.05; Histopathologic examination, remove 2 slight dilatation and congestion of (2/4) animal sinus hepaticus of heavy dose of group, outside the slight hepatic cell hydropic degeneration, other organizes no abnormality seen, in, the heart, liver, spleen, lung, kidney, brain, cerebellum, adrenal gland, testis, epididymis, prostate, uterus, ovary, thyroid, thymus, optic nerve, hypophysis, SDP gland, bladder, breastbone marrow, colon, ileum, spinal cord, the lymph node tissue of small dose group and each animal of matched group, there is no unusual.Drug withdrawal was observed 21 days, and the same histological examination is no abnormality seen also.To sum up: prompting fourth cassia oil 4.05g crude drug in whole/kg dosage may have the mild damage to hepatic tissue through continuous 100 days oral administrations of Beagle dog, and drug withdrawal can recover normally other each index is not had obvious influence.As seen fourth cassia oil soft capsule has characteristics safely and efficiently.

The specific embodiment

Prescription: Flos Caryophylli 50%, Cortex Cinnamomi 50% mixed extraction volatile oil, preparation fourth cassia oil.Fourth cassia oil 36ml, soybean oil 364ml, gelatin 150g, glycerol 60g deionized water 150g, simple syrup 10g, methyl parahydroxybenzoate 0.15g, the above supplementary material of ethylparaben 0.075g are made 1000 of soft capsules altogether.

Method for making: fourth cassia oil and soybean oil mixing, standby.Get gelatin, glycerol, simple syrup and add the deionized water mixing, be heated to 60～70 ℃, be incubated 0.5 hour, add methyl parahydroxybenzoate, ethylparaben, stir, evacuation, the capsule material is made in 70 ℃ of insulations 20 minutes.Get the mixture of fourth cassia oil and soybean oil, adopt pressing to make soft capsule with the capsule material.

Claims

1. Flos Caryophylli 50%, Cortex Cinnamomi 50% mixed extraction volatile oil prepare the fourth cassia oil.With the fourth cassia oil is main composition, adds adjuvant, and mixing is made the preparation that is used for irritable bowel syndrome.

2. Flos Caryophylli 50%, Cortex Cinnamomi 50% mixed extraction volatile oil prepare the fourth cassia oil.With the fourth cassia oil is main composition, adds adjuvant, and mixing is made the soft capsule that is used for irritable bowel syndrome.

3. extract volatile oil and make wherein effective ingredient eugenol, cinnamic aldehyde content sum between 50-98% from Flos Caryophylli, Cortex Cinnamomi, as main composition, add adjuvant, mixing is made soft capsule.Be used for the treatment of irritable bowel syndrome.