CN1616018A

CN1616018A - Preparation for improving bioavailability and medicine effect for treating gynecopathy and preparing method

Info

Publication number: CN1616018A
Application number: CNA2004100744997A
Authority: CN
Inventors: 叶耀良; 廖志钟
Original assignee: Individual
Current assignee: Guangdong Luofushan Sinopharm Co Ltd
Priority date: 2004-09-17
Filing date: 2004-09-17
Publication date: 2005-05-18
Anticipated expiration: 2024-09-17
Also published as: CN1268377C

Abstract

The gynecopathy treating medicine preparation with raised bioavailability and treating effect is prepared with seven kinds of Chinese medicinal materials, including heaven tree bark, schisandra, phellodendron bark, tortoise plastron, tuckahoe, etc. in certain proportion. The extract of the said medicine material, stuffing, disintegrating agent and lubricant are produced into dispersed tablet; the extract of the said medicine material, dispersing medium, suspension assistant and preservative are prepared into soft capsule; or, the extract of the said medicine material, stuffing, disintegrating agent and lubricant are prepared into capsule. The dispersed tablet, the soft capsule and the capsule are used in treating chronic pulvic infection, and have high curative effect and short treating period.

Description

A kind of preparation and preparation method that improves bioavailability and medicine effect for treating gynecopathy

Technical field

The present invention relates to a kind of preparation and preparation method that improves bioavailability and medicine effect for treating gynecopathy.

Technical background

FUKE ZHIDAI PIAN has the effect of heat clearing and damp drying, convergence leukorrhagia stopping, is used for chronic cervicitis, endometritis, the damp-heat type leucorrhea with red and white discharge disease that encolpitis etc. cause.Pharmacological research shows: FUKE ZHIDAI PIAN has:

1, resisting pathogenic microbes effect.For staphylococcus aureus, streptococcus, bacillus pyocyaneus, escherichia coli and Candida albicans etc. good fungistatic effect is arranged all.

2, antiinflammatory action.Can reduce capillary permeability, suppress inflammatory exudation and connective tissue, reaction reduces inflammation.

3, improve immunologic function, physical strength reinforcing.Can make Mus thymus, spleen weightening finish, strengthen the huge function of biting in abdominal cavity, enhancing body resisting fatigue, stress abilities such as anti-hypoxia.

Former dosage form is the conventional sugar garment piece, and patient's dose is big.And, easily by microbial contamination, product quality is descended in the production because the protide nutrient substance is more in the former prescription.Coated tablet is unsuitable for the use of sugar avoiding patient.

Along with the continuous variation and the human adaptive variation for medicine of environment, people have had higher requirement for the bioavailability and the drug effect of Chinese medicine.

Summary of the invention

The object of the invention is to add appropriate amount of auxiliary materials in the prescription medicinal substances extract based on Chinese medicine, and provide a kind of preparation and preparation method that improves bioavailability and medicine effect for treating gynecopathy, the present invention to take following design: the component weight proportion of gynaecologic leucorrhea removing preparation of the present invention is:

Cortex Ailanthi 300～426 Fructus Schisandrae Chinensis 50～78 Cortex Phellodendris 350～376

Carapax et Plastrum Testudinis 230～254 Poria 350～376 Colla Corii Asini 110～130 Rhizoma Dioscoreaes 350～376

The medicinal substances extract of above-mentioned component cooperates pharmaceutically alleged adjuvant that adopts suitable kind or soft capsule, dispersible tablet, the capsule that substrate is made; As making soft capsule with one or more of disperse medium, suspending agent, antiseptic; Or with filler, disintegrating agent, wetting agent, lubricant one or more make dispersible tablet, or one or more make capsule with filler, disintegrating agent, lubricant.

Or make dispersible tablet with filler (60～500), disintegrating agent (10～160), lubricant (1～5); Or make soft capsule with disperse medium (60～400), suspending agent (3～40), antiseptic (0.1～3); Or make capsule with filler (80～450), disintegrating agent (10～80), lubricant (1～8).

Its preparation process may further comprise the steps:

Step 1: the Cortex Ailanthi of getting above-mentioned share adds 6～15 times of amounts of water and decocts secondary, and each 2 hours, collecting decoction filtered, and filtrate is concentrated in right amount (40 ℃ of relative densities 1.20～1.35), adds ethanol and makes and contain the alcohol amount and be about 50%, leaves standstill filtration; The Cortex Phellodendri of getting above-mentioned share is with 85% alcohol reflux three times, and each 1.5 hours, merge extractive liquid, filtered; The Poria of getting above-mentioned share with 60% ethanol, the Rhizoma Dioscoreae of getting the Fructus Schisandrae Chinensis of above-mentioned share and getting above-mentioned share with 45% ethanol according to " percolation under Chinese pharmacopoeia fluid extract and the extractum item carries out percolation; More than each liquid reclaim ethanol respectively and be condensed into thick paste; The Carapax et Plastrum Testudinis water of getting above-mentioned share embathes except that the fleshing bits, adds 5～10 times of amounts of water and decocts secondary, and each 6 hours, collecting decoction filtered, and filtrate is condensed into gluey thick paste; Filtering residue dries, and is ground into coarse powder, with 10% acetum dipping, filters the filtrate evaporate to dryness; The Colla Corii Asini of getting above-mentioned share is ground into 100 order fine powders after with stir-baked in powder of CONCHA MERETRICIS SEU CYCLINAE, sieve, with above-mentioned each thick paste and acetic acid extractum mix homogeneously, extract, standby.

Step 2: get antiseptic, suspending agent, the oil phase disperse medium mixing and stirring of described share, be preheated to 60～65 ℃, be soft capsule liquid grinding homogenizing, be pressed into soft capsule with 1 extract obtained mixing of above-mentioned steps;

Or step 3: it is extract obtained to get step 1, dry, be crushed to 80 orders or thinner, with filler, the disintegrating agent mix homogeneously of described share, with the bonding granulation of the wetting agent of described share, drying, granulate, add the lubricant tabletting of described share, promptly get the gynaecologic leucorrhea removing dispersible tablet, or make coated dispersing tablet through film coating again; Disintegrating agent can add before and after granulating in gradation in the process;

Or step 4: it is extract obtained to get step 1, and with filler, the disintegrating agent mix homogeneously of described share, drying is crushed to 80 orders or thinner, with the bonding granulation of wetting agent, and drying, granulate adds lubricant, and the fill capsule promptly gets capsule; Or the extract pulverizing, even with filler, the mix lubricant of described share, directly the fill capsule also can make capsule;

Or get the recovery ethanol clear paste merging that step 1 obtains, and spray drying, the powder that gets dry extract is standby, gets the Carapax et Plastrum Testudinis acetic acid macerate that step 1 obtains, and Colla Corii Asini is fried the back and is pulverized, and all is crushed to 80 orders or thinner.Get the disintegrating agent mix homogeneously of dried cream powder, pulverizing back Carapax et Plastrum Testudinis acetic acid macerate, donkey-hide gelatin fine powder, the filler of above-mentioned share, above-mentioned share, with the bonding granulation of the wetting agent of above-mentioned share, drying, granulate, the fill capsule also gets the gynaecologic leucorrhea removing capsule.

Effect of the present invention:

The clinical efficacy demonstration test of damp heat downward flowing type under gynaecologic leucorrhea removing soft capsule, the dispersible tablet treatment belt

One, research background:

Leukorrheal diseases are a commonly encountered diseases, frequently-occurring disease, clinically rather see that Chinese medicine adopts the traditional decoction treatment more more.FUKE ZHIDAI PIAN is clinical medicine comparatively commonly used, but it is slow to produce effects, and the course of treatment is long, easily recurrence.

Gynaecologic leucorrhea removing side's modern pharmacological research shows that it has:

This confirmatory experiment is judged the curative effect difference of estimating damp heat downward flowing type and gynaecologic leucorrhea removing ordinary tablet under gynaecologic leucorrhea removing soft capsule, the dispersible tablet treatment belt from tcm diagnosis, curative effect.

Gynecological Chinese medicine preparation of the present invention can effectively be treated symptoms such as multiple gynecological leukorrhagia, soreness of waist pain.Through more than 2 years to 240 routine leukorrhagia patients' clinical observation, obtained curative effect preferably.

Two, patient profile

Since two thousand two, we use homemade gynaecologic leucorrhea removing soft capsule, gynaecologic leucorrhea removing dispersible tablet treatment leukorrheal diseases 160 examples, have obtained satisfactory effect.Now be reported as follows.

The patient source

Whole cases are totally 240 examples, are the outpatient.Age 20-66 year, average 40 years old.The course of disease 1-36 month.Urban residents' 168 examples wherein, town dweller's 88 examples.It is divided into three groups at random, each 80 example of gynaecologic leucorrhea removing capsule for treating group, gynaecologic leucorrhea removing dispersible tablet treatment group and FUKE ZHIDAI PIAN matched group.

Inclusion criteria

Diagnostic criteria is cured the damp heat downward flowing type that gynecological's disease is diagnosed " diagnosis basis of leukorrheal diseases, card marquis classification, the efficacy evaluation " of criterion of therapeutical effect among adopting People's Republic of China's Chinese medicine industry standard.

This standard is concluded leukorrheal diseases system and is dashed by the damp influence and appoint, and dai channel is failed to keep an appointment, and conception vessel loses solid, causes the abnormal change of the many or color of vaginal secretions amount, matter, abnormal smells from the patient.Be more common in diseases associated with inflammation such as vagina, cervix uteri.

Three, diagnosis basis

3.1 profuse leukorrhea continues for ever.

Though 3.2 the leukorrhagia amount is few, yellow skin is red or dark green; Matter is thick turbid or clear rare as water, stink smell or stench.

3.3 must differentiate mutually with the malignant tumor of fallopian tube and body of uterus, neck.

The syndrome diagnostic criteria

The leukorrhagia damp heat downward flowing type: the secretions amount is many, yellow skin or double green, and the matter thickness, or as bean dregs, or like foam, gas is dirty or smelly, the scorching hot pruritus of vaginal orifice, and oliguria with reddish urine, or with the abdominal part dragging pain.Red tongue, yellow and greasy fur, arteries and veins scholar number.Headache bitter taste, irritated irritability, constipation with dry stool breast side of body distending pain appears, in double dampness-heat in the liver and gallbladder person.Red tongue, yellow fur, wiry and frequent pulse.

Four, Therapeutic Method:

Take gynaecologic leucorrhea removing coated tablet, dispersible tablet, soft capsule treatment merely, have obvious inflammation person to take antibiotic, vitamin deficiency symptom patient is arranged, give vitamin in right amount.Cut out other adjusting meridian and stopping leukorrhea class Chinese-western medicine preparations during the patient treatment.

Instructions of taking:

Treatment group 1 (soft capsule group): oral, one time 2～3,2～3 times on the one.

Treatment group 2 (dispersible tablet group): oral, one time 4～6,2～3 times on the one.

Matched group (conventional tablet group): oral, one time 4～6,2～3 times on the one.

Five, EXPERIMENTAL DESIGN and efficacy evaluation

5.1 cure: the amount of vaginal secretions, color, abnormal smells from the patient, matter are all recovered normally, all diseases disappear.

5.2 produce effects: the amount of vaginal secretions, color, abnormal smells from the patient, matter and all diseases alleviate obviously, and tongue arteries and veins accompanied symptoms improves.

5.3 effectively: the amount of vaginal secretions, color, abnormal smells from the patient, matter and all diseases alleviate very unobvious, tongue arteries and veins accompanied symptoms improves.

5.4 it is invalid: all disease no changes of leukorrhagia.

Six, efficacy analysis

Soft capsule group one example comes off because of losing to visit, and matched group one example is because of taking other adjusting meridian and stopping leukorrhea Chinese medicines so do not include summary in, and curative effect is summarized as follows table

Table 1 case curative effect of disease relatively

Recovery from illness produce effects enabledisable

Total example

Group % % example

The numerical example numerical example is counted % example number %

Number

27. 30.5

Soft capsule group 79 22 24 31 39.2 2 2.5

8

30. 28.8

Dispersible tablet group 80 24 23 30 37.5 2 2.5

0

23. 27.8 10.

Matched group 79 15 22 35 44.3 8

8 1

Learn check by statistics, Ridit analyzes: soft capsule group, dispersible tablet group have raising than the matched group total effective rate, P＜0.05.Significantly be better than matched group, P＜0.01 from cure rate analysis dispersible tablet, soft capsule group.

Table 2, onset time synopsis

Average effective time average cure time

The total routine number of group

Example number day number of drug administration example number day number of drug administration

Soft capsule group 79 24 14 22 21

Dispersible tablet group 80 24 14 24 21

Matched group 79 22 21 15 28

The analysis showed that by statistics soft capsule group, dispersible tablet group onset time, average cure time is short than matched group onset time, (p＜0.01).Between soft capsule, the dispersible tablet group, onset time, healing time does not have significant difference.

Seven, conclusion:

Leukorrheal diseases motherland medical science thinks that it is mark that damp invasion of lower energizer causes leukorrhagia because insufficiency of the spleen mistake is transported, suffering from a deficiency of the kidney to lose is this admittedly.Control from the eight extra-channel opinion, then belong to appoint, band, thus dai channel is failed to keep an appointment, conception vessel not because of form.Clinical in leukorrhagia amount showed increased, color, matter, foul smell are unusual.Or, claim leukorrheal diseases with whole body and local symptom person.Gynaecologic leucorrhea removing is worked out based on above-mentioned cognition.

In the side, Rhizoma Dioscoreae, Poria spleen invigorating are dried, and astringent therapy is held back in Fructus Schisandrae Chinensis, Cortex Ailanthi acid, the clear damp-heat in lower-JIAO of Cortex Phellodendri, Carapax et Plastrum Testudinis, kind conception vessel dai channel, the effect of playing the damp eliminating leukorrhagia stopping altogether of mending of Colla Corii Asini.

Innovation dosage form treatment leukorrheal diseases are rapid-action, short treating period, and medicine is inexpensive, and through clinical verification, the more former gynaecologic leucorrhea removing therapeutic effect of effect, onset time are excellent.

Clinical observation shows: gynaecologic leucorrhea removing soft capsule, gynaecologic leucorrhea removing dispersible tablet, gynaecologic leucorrhea removing capsule for treating chronic pelvic inflammatory disease, course of disease weak point person curative effect is good especially, compares with FUKE ZHIDAI PIAN, can obviously shorten administration time.Therapeutic effect is better than FUKE ZHIDAI PIAN through check, and cure rate is higher.

Advantage of the present invention is:

Soft capsule: the soft capsule introduction also claims the flexible glue pill, and it is not have a kind of preparation that forms in sealings such as the non-water-soluble liquid of dissolution or suspension and the capsule shells with oils or to the gelatin thing.Soft capsule is the tablet that continues, and a kind of novel form that grows up after the injection, its shell are to form with the gelatin compacting, the aqueous medicinal liquid of bag in the softgel shell.Be characterized in slower than injection onset, but than tablet, capsule, granule is rapid-action.More easy to carry than oral liquid.Because the optimization of soft capsule liquid of the present invention prescription, its content can be in human body self emulsifying to a certain degree, increase absorption area, thus the bioavailability height.

Dispersible tablet: be a kind of solidified liquid form of administration, disintegrate fully in 3 minutes at normal temperatures, the effective ingredient stripping is rapid.But solid state is taken, but also liquid condition is taken, and makes things convenient for the patient.The development of dispersible tablets of Chinese medicine need overcome and extract the difficult point that the extractum moisture absorption influences disintegrate, and the present invention is by the screening adjuvant, thereby it is stable to reach end product quality, and disintegrate is characteristics rapidly.

Capsule: capsule is with respect to Chinese medical concrete sheet, coated tablet, and disintegrate is accelerated, and bioavailability improves, but because the hygroscopicity of Chinese medicine extraction extractum, a lot of Chinese medicinal capsules must be selected appropriate adjuvant in adjuvant is selected, just can overcome the hygroscopicity of extracting extractum, guarantee the quality of capsule finished product.

Former tablet is taken 4～6 at every turn, and every day, dose reached 18, and the patient uses very inconvenience.The patient buys poor selectivity, perhaps because of taking the relatively poor often therapy discontinued of mouthfeel.The present invention has finished the adjuvant of above-mentioned novel form and has selected, and by the gynaecologic leucorrhea removing prescription is made above-mentioned novel form, it is convenient that the patient is taken, thereby can follow the doctor's advice, and finishes the treatment of the corresponding course of treatment.

The specific embodiment: the component among the embodiment all is the component weight proportion;

Embodiment 1: used medical material component weight proportion is:

Cortex Ailanthi 300g Fructus Schisandrae Chinensis 50g Cortex Phellodendri 350g

Carapax et Plastrum Testudinis 230g Poria 350g Colla Corii Asini 110g Rhizoma Dioscoreae 350g

Its preparation process may further comprise the steps:

Step 1: the Cortex Ailanthi of getting described share adds 6 times of amounts of water and decocts secondary, and each 2 hours, collecting decoction filtered, and filtrate is concentrated in right amount (40 ℃ of relative densities 1.20), adds ethanol and makes and contain the alcohol amount and be about 50%, leaves standstill filtration;

Step 2: the Cortex Phellodendri of getting described share is with 85% alcohol reflux three times, and each 1.5 hours, merge extractive liquid, filtered;

Step 3: the Poria of getting described share carries out percolation with 45% ethanol according to the percolation under fluid extract and the extractum item with 60% ethanol, the Rhizoma Dioscoreae of getting the Fructus Schisandrae Chinensis of described share and getting described share; More than each liquid reclaim ethanol respectively and be condensed into thick paste;

Step 4: the Carapax et Plastrum Testudinis water of getting described share embathes except that the fleshing bits, adds 5 times of amounts of water and decocts secondary, and each 6 hours, collecting decoction filtered, and filtrate is condensed into gluey thick paste; Filtering residue dries, and is ground into coarse powder, with 10% acetum dipping, filters the filtrate evaporate to dryness;

Step 5: the Colla Corii Asini of getting described share is ground into 100 order fine powders after with stir-baked in powder of CONCHA MERETRICIS SEU CYCLINAE, sieve, with above-mentioned each thick paste and acetic acid extractum mix homogeneously, extract, standby.

Embodiment 2: used medical material component weight proportion is:

Cortex Ailanthi 363g Fructus Schisandrae Chinensis 64g Cortex Phellodendri 363g

Carapax et Plastrum Testudinis 242g Poria 363g Colla Corii Asini 120g Rhizoma Dioscoreae 363g

Its preparation process may further comprise the steps:

Step 1: the Cortex Ailanthi of getting described share adds 8 times of amounts of water and decocts secondary, and each 2 hours, collecting decoction filtered, and filtrate is concentrated in right amount (40 ℃ of relative densities 1.25), adds ethanol and makes and contain the alcohol amount and be about 50%, leaves standstill filtration;

Step 4: the Carapax et Plastrum Testudinis water of getting described share embathes except that the fleshing bits, adds 8 times of amounts of water and decocts secondary, and each 6 hours, collecting decoction filtered, and filtrate is condensed into gluey thick paste; Filtering residue dries, and is ground into coarse powder, with 10% acetum dipping, filters the filtrate evaporate to dryness;

Embodiment 3: used medical material component weight proportion is:

Cortex Ailanthi 426g Fructus Schisandrae Chinensis 78g Cortex Phellodendri 376g

Carapax et Plastrum Testudinis 254g Poria 376g Colla Corii Asini 130g Rhizoma Dioscoreae 376g

Its preparation process may further comprise the steps:

Step 1: the Cortex Ailanthi of getting described share adds 15 times of amounts of water and decocts secondary, and each 2 hours, collecting decoction filtered, and filtrate is concentrated in right amount (40 ℃ of relative densities 1.35), adds ethanol and makes and contain the alcohol amount and be about 50%, leaves standstill filtration;

Step 4: the Carapax et Plastrum Testudinis water of getting described share embathes except that the fleshing bits, adds 10 times of amounts of water and decocts secondary, and each 6 hours, collecting decoction filtered, and filtrate is condensed into gluey thick paste; Filtering residue dries, and is ground into coarse powder, with 10% acetum dipping, filters the filtrate evaporate to dryness;

Embodiment 4: the gynaecologic leucorrhea removing preparation of soft capsule

Used adjuvant component weight proportion is:

Suspending agent Cera Flava 3g;

Disperse medium olive oil 60g;

Preservative propylene glycol 0.1g

Emulsifying agent soybean lecithin 20g;

Step 1: get the medicinal substances extract after Cortex Ailanthi that embodiment 1 or embodiment 2 or embodiment 3 each step obtain and Fructus Schisandrae Chinensis and Cortex Phellodendri and Carapax et Plastrum Testudinis and Poria and Colla Corii Asini and Rhizoma Dioscoreae are handled,

Step 2: get in the antiseptic, suspending agent, disperse medium (being preheated to 60 ℃) of above-mentioned share standby; Mixing and stirring, and mix with above-mentioned medicinal substances extract and to be soft capsule liquid and to grind homogenizing, be pressed into soft capsule.

Or in above-mentioned step, or do not add disperse medium; Or do not add suspending agent; Or adding preservative agent not; Or one or more of disperse medium, suspending agent, antiseptic of getting above-mentioned share are made soft capsule.

Olive oil is that disperse medium also can be: the triglyceride oils of crude vegetal (soybean oil, Oleum Arachidis hypogaeae semen) or long-chain and medium-chain saturation in various degree, as: oleic acid sorbitol ester, olein: propylene glycol (90: 10), Oleum Cocois C8/C10 monoglyceride or dibasic acid esters, Oleum Cocois C8/C10 propylene glycol ester, Oleum Cocois triglyceride, the acetylizad monoglyceride of purification (Myvacet oil), olein, glyceryl linoleate, Polyethylene Glycol glyceryl laurate ester, purification Oleum helianthi monoglyceride.

Adjuvant in its soft capsule liquid process for preparation such as emulsifying agent, antiseptic;

1) its emulsifying agent can be soybean lecithin or select for use nonionic emulsifier be liquid egg phospholipid or polyoxyethylene castor oil or Oleum Cocois C8/C10 polyethyleneglycol glyceride or almond oil acid polyethylene glycol glyceride or polyoxyethylene (25) triolein or tween 80 or Polyethylene Glycol-8-glycerol sad/decanoin;

2) antiseptic is in its soft capsule: one or more in glycerol or propylene glycol or methyl parahydroxybenzoate or ethylparaben or propyl p-hydroxybenzoate or butyl p-hydroxybenzoate or benzyl p-hydroxybenzoate or the P-hydroxybenzoic acid phenyl ester.

The suspending agent of making soft capsule is: can increase the solid matter of disperse medium viscosity, as Cera Flava or aluminum monostearate or ethyl cellulose etc.; The best component weight proportion Cera Flava that uses: ethyl cellulose 6: 4.

Embodiment 5: the gynaecologic leucorrhea removing preparation of soft capsule

Used adjuvant component weight proportion is:

Suspending agent Cera Flava 10g;

Disperse medium natural plants 150g;

Preservative propylene glycol 2g;

Emulsifying agent soybean lecithin 20g;

Step 2: antiseptic, suspending agent, the disperse medium of getting above-mentioned share are preheated in 61 ℃ standby; Mixing and stirring, and mix with above-mentioned medicinal substances extract and to be soft capsule liquid and to grind homogenizing, be pressed into soft capsule.

Or in above-mentioned step, or do not add disperse medium; Or do not add suspending agent; Or adding preservative agent not; Or one or more of disperse medium, suspending agent, antiseptic of getting above-mentioned share are made soft capsule.Olive oil is that disperse medium also can be: described oiliness disperse medium is: the triglyceride oils of crude vegetal soybean oil or Oleum Arachidis hypogaeae semen or long-chain and medium-chain saturation in various degree; oleic acid sorbitol ester or olein: propylene glycol (90: 10) or Oleum Cocois C8/C10 monoglyceride or dibasic acid esters or Oleum Cocois C8/C10 propylene glycol ester or Oleum Cocois triglyceride or the acetylizad monoglyceride of purification or olein or glyceryl linoleate or Polyethylene Glycol glyceryl laurate ester or purification Oleum helianthi monoglyceride, or the best Oleum Cocois that uses: olein 9: 1.

Embodiment 6: the gynaecologic leucorrhea removing preparation of soft capsule

Used adjuvant component weight proportion is:

Suspending agent Cera Flava 40g;

Disperse medium oleic acid sorbitol ester 400g;

Preservative propylene glycol 3g;

Emulsifying agent soybean lecithin 20g;

Step 2: antiseptic, suspending agent, the disperse medium of getting above-mentioned share are preheated in 65 ℃ standby; Mixing and stirring, and mix with above-mentioned medicinal substances extract and to be soft capsule liquid and to grind homogenizing, be pressed into soft capsule.

Olive oil is that disperse medium also can be: described oiliness disperse medium is: the triglyceride oils of crude vegetal soybean oil or Oleum Arachidis hypogaeae semen or long-chain and medium-chain saturation in various degree; oleic acid sorbitol ester or olein: propylene glycol (90: 10) or Oleum Cocois C8/C10 monoglyceride or dibasic acid esters or Oleum Cocois C8/C10 propylene glycol ester or Oleum Cocois triglyceride or the acetylizad monoglyceride of purification or olein or glyceryl linoleate or Polyethylene Glycol glyceryl laurate ester or purification Oleum helianthi monoglyceride, or the best Oleum Cocois that uses: olein 9: 1.

Make soft capsule disperse medium or for oiliness disperse medium or PEG400 or Polyethylene Glycol 500 or Macrogol 600 or isopropyl alcohol or glycerol or propylene glycol and water one or more; Or the best oiliness disperse medium that uses.

Embodiment 7: the gynaecologic leucorrhea removing preparation of soft capsule

Used adjuvant component weight proportion is:

PEG400 200g

Glycerol 7g

Water 25ml

Tween 80 0.5g

Step 2: the Polyethylene Glycol of getting above-mentioned share is preheated to 40 ℃, adds glycerol, the water tween of above-mentioned share, and supersound process makes mix homogeneously; The material extract fine powder of getting it filled mixes with it, stirs, and grinds homogenizing, makes the gynaecologic leucorrhea removing soft capsule.

Embodiment 8: the gynaecologic leucorrhea removing preparation of soft capsule

Used adjuvant component weight proportion is:

PEG400 130g

Glycerol 7g

Water 25ml

Tween 80 0.5g

Embodiment 9: the preparation of gynaecologic leucorrhea removing dispersible tablet

Used adjuvant component weight proportion is:

Filler: 40 parts of pregelatinized Starch and 20 parts of compositions of lactose;

10 parts of disintegrating agents;

Lubricant is 1 part of a magnesium stearate;

Correctives is 0.5 part of an xylitol;

Step 2: get the recovery ethanol clear paste merging that step 1 obtains, spray drying, the powder that gets dry extract is standby, gets the Carapax et Plastrum Testudinis acetic acid macerate that step 1 obtains, and Colla Corii Asini is fried the back and is pulverized, and all pulverizes 80 orders or thinner; Get dried cream powder, pulverize the disintegrating agent mix homogeneously of back Carapax et Plastrum Testudinis acetic acid macerate, donkey-hide gelatin fine powder, the filler of above-mentioned share, above-mentioned share, with the bonding granulation of wetting agent, drying, granulate adds the lubricant tabletting of above-mentioned share, promptly gets the gynaecologic leucorrhea removing dispersible tablet; Or wherein disintegrating agent can add before and after granulating in gradation.

Or in above-mentioned step, or do not add filler; Or not with disintegrating agent; Or do not add wetting agent; Or make dispersible tablet with one or more of filler, disintegrating agent, wetting agent.

Crospolyvinylpyrrolidone is a The disintegrating agents of dispersible tablets, removes crospolyvinylpyrrolidone can also be: carboxymethyl starch sodium or low-substituted hydroxypropyl cellulose or cross-linked carboxymethyl cellulose sodium.

The dilute alcohol solution of polyvinylpyrrolidone is the wetting agent in the dispersible tablet.Wetting agent in its dispersible tablet can also be 40% ethanol～95% alcoholic solution or starch slurry or polyvinylpyrrolidone Alcoholic solution

Alcoholic solution or starch slurry or polyvinylpyrrolidone Alcoholic solution

Magnesium stearate lubricant in the above-mentioned dispersible tablet can also be: micropowder silica gel or Pulvis Talci.

Correctives xylitol in the above-mentioned dispersible tablet can also be sweet or mannitol or other medicinal correctives of A Basi.

Embodiment 10: the preparation of gynaecologic leucorrhea removing dispersible tablet

Used adjuvant component weight proportion is:

Filler: pregelatinized Starch 80g and lactose 40g;

Disintegrating agent 50g;

Lubricant: magnesium stearate 1.5g;

Correctives is xylitol 3g;

Step 2: it is extract obtained to get step 1, and with filler, the disintegrating agent mix homogeneously of described share, drying is crushed to 80 orders or thinner, with the bonding granulation of wetting agent, and drying, granulate adds lubricant, and the fill capsule promptly gets capsule; Or the extract pulverizing, even with filler, disintegrating agent, the mix lubricant of described share, directly the fill capsule also can make capsule.

Step 3: or get the recovery ethanol clear paste merging that step 1 obtains, spray drying, the powder that gets dry extract is standby, gets the Carapax et Plastrum Testudinis acetic acid macerate that step 1 obtains, and Colla Corii Asini is fried the back and is pulverized, and all is crushed to 80 orders or thinner; Get dried cream powder, pulverize the disintegrating agent mix homogeneously of back Carapax et Plastrum Testudinis acetic acid macerate, donkey-hide gelatin fine powder, the filler of above-mentioned share, above-mentioned share, with the bonding granulation of wetting agent, drying, granulate adds the lubricant tabletting of above-mentioned share, promptly gets the gynaecologic leucorrhea removing dispersible tablet; Or wherein disintegrating agent can add before and after granulating in gradation.

The dilute alcohol solution of polyvinylpyrrolidone is the wetting agent in the dispersible tablet.Wetting agent in its dispersible tablet can also be 40% ethanol～95% alcoholic solution or starch slurry or polyvinylpyrrolidone Alcoholic solution, alcoholic solution or starch slurry or polyvinylpyrrolidone Alcoholic solution

Its The disintegrating agents of dispersible tablets is: crospolyvinylpyrrolidone or carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, cross-linked carboxymethyl cellulose sodium one or more, the best is a carboxymethyl starch sodium: the mixture of low-substituted hydroxypropyl cellulose (1: 3).

Embodiment 11: the preparation of gynaecologic leucorrhea removing dispersible tablet

Used adjuvant component weight proportion is:

Filler: pregelatinized Starch 300g and lactose 200g;

Disintegrating agent 160g;

Lubricant: magnesium stearate 5g;

Step 2: it is extract obtained to get step 1, and with filler, the disintegrating agent mix homogeneously of described share, drying is crushed to 80 orders or thinner, with the bonding granulation of wetting agent, and drying, granulate adds lubricant, and the fill capsule promptly gets capsule; Or the extract pulverizing, even with filler, disintegrating agent, the mix lubricant of described share, directly the fill capsule also can make capsule;

Alcoholic solution or starch slurry or polyvinylpyrrolidone Alcoholic solution

Lubricant in its dispersible tablet is magnesium stearate or micropowder silica gel or Pulvis Talci.

Embodiment 12: the capsular preparation of gynaecologic leucorrhea removing

Used adjuvant component weight proportion is:

Filler: starch 40g: precoking starch 10g

Disintegrating agent hangs down substituted carboxymethyl sodium cellulosate 2g;

Lubricant: micropowder silica gel 1g;

Step 2: it is extract obtained to get step 1, and with filler, the disintegrating agent mix homogeneously of described share, drying is crushed to 80 orders or thinner, with the bonding granulation of wetting agent, and drying, granulate adds lubricant, and the fill capsule promptly gets capsule; Or the extract pulverizing, even with filler, the mix lubricant of described share, directly the fill capsule also can make capsule; When being direct powder fill, need not use disintegrating agent.

Filler during its preparation capsule is: starch or lactose or microcrystalline Cellulose or precoking starch etc., or the best is a starch: precoking starch 6: 1; Disintegrating agent is: Sodium Tvlose or precoking starch or microcrystalline Cellulose or crospolyvinylpyrrolidone or low substituted carboxymethyl sodium cellulosate or low-substituted hydroxypropyl cellulose or polyvinylpyrrolidone, or best for hanging down the substituted carboxymethyl sodium cellulosate.Carboxymethylstach sodium 1: 1

The capsular preparation of embodiment 13 gynaecologic leucorrhea removings

Used adjuvant component weight proportion is:

Filler: starch 60g: precoking starch 20g

Disintegrating agent hangs down substituted carboxymethyl sodium cellulosate 6g;

Lubricant: magnesium stearate 1g;

Step 2: get the recovery ethanol clear paste merging that step 1 obtains, spray drying, the powder that gets dry extract is standby, gets the Carapax et Plastrum Testudinis acetic acid macerate that step 1 obtains, and Colla Corii Asini is fried the back and is pulverized, and all is crushed to 80 orders or thinner.Get the disintegrating agent mix homogeneously of dried cream powder, pulverizing back Carapax et Plastrum Testudinis acetic acid macerate, donkey-hide gelatin fine powder, the filler of above-mentioned share, above-mentioned share, with the bonding granulation of the wetting agent of above-mentioned share, drying, granulate, the fill capsule promptly gets the gynaecologic leucorrhea removing capsule.Or the extract pulverizing, even with filler, the mix lubricant of described share, directly the fill capsule also can make capsule.When being direct powder fill, need not use disintegrating agent, wetting agent.

Described wetting agent (or claiming binding agent) is: 40% ethanol～95% alcoholic solution, or starch slurry, or the alcoholic solution of polyvinylpyrrolidone; Or the best is 50% alcoholic solution of 2～4% polyvinylpyrrolidones etc. one or more.

Filler during its preparation capsule is: starch or lactose or microcrystalline Cellulose or precoking starch etc., or the best is a starch: precoking starch 6: 1; Disintegrating agent is: Sodium Tvlose or precoking starch or microcrystalline Cellulose or crospolyvinylpyrrolidone or low substituted carboxymethyl sodium cellulosate or low-substituted hydroxypropyl cellulose or polyvinylpyrrolidone, or best for hanging down the substituted carboxymethyl sodium cellulosate: carboxymethylstach sodium 1: 1.

The capsular preparation of embodiment 14 gynaecologic leucorrhea removings

Used adjuvant component weight proportion is:

Filler: starch 320g: precoking starch 130g

Disintegrating agent hangs down substituted carboxymethyl sodium cellulosate 20g;

Lubricant: magnesium stearate 8g;

Step 2: the recovery ethanol clear paste of above-mentioned steps one merges, spray drying, and the powder that gets dry extract is standby, Carapax et Plastrum Testudinis acetic acid macerate, Colla Corii Asini is fried the back and is pulverized, and all is crushed to 80 orders or thinner.Get the disintegrating agent mix homogeneously of dried cream powder, pulverizing back Carapax et Plastrum Testudinis acetic acid macerate, donkey-hide gelatin fine powder, the filler of above-mentioned share, above-mentioned share, with the bonding granulation of the wetting agent of above-mentioned share, drying, granulate, the fill capsule promptly gets the gynaecologic leucorrhea removing capsule.

Or the extract pulverizing, even with filler, the mix lubricant of described share, directly the fill capsule also can make capsule.When being direct powder fill, need not use disintegrating agent, wetting agent.

The capsular preparation of embodiment 15 gynaecologic leucorrhea removings

Used adjuvant component weight proportion is:

Filler: starch 320g: precoking starch 130g

Lubricant: magnesium stearate 8g;

Step 2: it is extract obtained to get step 1, and with the filler mix homogeneously of described share, drying is crushed to 80 orders or thinner, with the bonding granulation of wetting agent, and drying, granulate adds lubricant, and the fill capsule promptly gets capsule; Or the extract pulverizing, even with filler, the mix lubricant of described share, directly the fill capsule also can make capsule.When being direct powder fill, need not use disintegrating agent, wetting agent.。

Filler during its preparation capsule is: starch or lactose or microcrystalline Cellulose or precoking starch etc., or the best is a starch: precoking starch 6: 1.

Claims

1, a kind of preparation that improves bioavailability and medicine effect for treating gynecopathy, used medical material is weight set of dispense ratio:

Carapax et Plastrum Testudinis 230～254 Poria 350～376 Colla Corii Asini 110～130

Rhizoma Dioscoreae 350～376

The medicinal substances extract of above-mentioned component cooperates pharmaceutically alleged adjuvant that adopts suitable kind or soft capsule, dispersible tablet, the capsule that substrate is made; As making soft capsule with one or more of disperse medium, suspending agent, antiseptic; Or make dispersible tablet, or make capsule with one or more of filler, disintegrating agent, lubricant with one or more of filler, disintegrating agent, wetting agent.

2, a kind of preparation that improves bioavailability and medicine effect for treating gynecopathy according to claim 1, it is characterized in that: the optimum weight component proportioning of its used medical material is:

Cortex Ailanthi 363 Fructus Schisandrae Chinensis 64 Cortex Phellodendris 363

Carapax et Plastrum Testudinis 242 Poria 363g Colla Corii Asini 120 Rhizoma Dioscoreaes 363

Or make dispersible tablet with filler (60～500), disintegrating agent (10～160), lubricant (1～5); Or make soft capsule with disperse medium (60～400), suspending agent (3～40), antiseptic (0.1～3); Or make capsule with filler (50～450), disintegrating agent (2～20), lubricant (1～8).

3, according to claim 1 or 2 described a kind of preparation methoies that improve the preparation of bioavailability and medicine effect for treating gynecopathy, its preparation process may further comprise the steps:

Step 1: the Cortex Ailanthi of getting described share adds 6～15 times of amounts of water and decocts secondary, and each 2 hours, collecting decoction filtered, and filtrate is concentrated in right amount, adds ethanol and makes and contain the alcohol amount and be about 50%, leaves standstill filtration; The Cortex Phellodendri of getting described share is with 85% alcohol reflux three times, and each 1.5 hours, merge extractive liquid, filtered; The Poria of getting described share with 60% ethanol, the Rhizoma Dioscoreae of getting the Fructus Schisandrae Chinensis of described share and getting described share with 45% ethanol according to " percolation under Chinese pharmacopoeia fluid extract and the extractum item carries out percolation; More than each liquid reclaim ethanol respectively and be condensed into thick paste; The Carapax et Plastrum Testudinis water of getting described share embathes except that the fleshing bits, adds 5～10 times of amounts of water and decocts secondary, and each 6 hours, collecting decoction filtered, and filtrate is condensed into gluey thick paste; Filtering residue dries, and is ground into coarse powder, with 10% acetum dipping, filters the filtrate evaporate to dryness; The Colla Corii Asini of getting described share is ground into 100 order fine powders after with stir-baked in powder of CONCHA MERETRICIS SEU CYCLINAE, sieve, with above-mentioned each thick paste and acetic acid extractum mix homogeneously, extract, standby;

Step 2: get antiseptic, suspending agent, the oil phase disperse medium mixing and stirring of described share, be preheated to 60～65 ℃, be soft capsule content grinding homogenizing, make soft capsule with 1 extract obtained mixing of above-mentioned steps;

Or step 4: it is extract obtained to get step 1, and with filler, the disintegrating agent mix homogeneously of described share, drying is crushed to 80 orders or thinner, with the bonding granulation of wetting agent, and drying, granulate adds lubricant, and the fill capsule promptly gets capsule; Or the extract pulverizing, even with filler, the mix lubricant of described share, directly the fill capsule also can make capsule.

4, according to claim 1 and 2 described a kind of preparations that improve bioavailability and medicine effect for treating gynecopathy, it is characterized in that: the extract of above-mentioned used medical material with the component weight proportion of the basic adjuvant of the best is:

Soft capsule matrix and adjuvant: disperse medium 150; Suspending agent 10;

Dispersible tablet adjuvant: filler 120, disintegrating agent 50, lubricant 1.5;

Capsule adjuvant: filler 80, disintegrating agent 6, lubricant 2.

5, according to claim 1 and 2 described a kind of preparations that improve bioavailability and medicine effect for treating gynecopathy, it is characterized in that: the disperse medium of making soft capsule is: one or more of oiliness disperse medium or water solublity disperse medium; Or the best oiliness disperse medium that uses.

6, a kind of preparation that improves bioavailability and medicine effect for treating gynecopathy according to claim 5 is characterized in that:

Making the used oiliness disperse medium of soft capsule is: olive oil, or other crude vegetals, as soybean oil, Oleum Arachidis hypogaeae semen, or triglyceride oils, or oleic acid sorbitol ester, or component weight proportion olein: propylene glycol (90: 10), or Oleum Cocois C8/C10 monoglyceride or dibasic acid esters, or Oleum Cocois C8/C10 propylene glycol ester, or the Oleum Cocois triglyceride, or the acetylizad monoglyceride of purification, or olein, or glyceryl linoleate, or the Polyethylene Glycol glyceryl laurate ester, or one or more of purification Oleum helianthi monoglyceride etc., or best operating weight set of dispense is than olive oil: Oleum Arachidis hypogaeae semen 7: 3;

Making the used water-soluble medium of soft capsule is: molecular weight is one or more of 200 to 800 Polyethylene Glycol, isopropyl alcohol, glycerol, propylene glycol, water etc.

7, according to claim 1 and 2 described a kind of preparations that improve bioavailability and medicine effect for treating gynecopathy, it is characterized in that: the suspending agent of making soft capsule is: can increase the solid matter of disperse medium viscosity, as one or more of Cera Flava or aluminum monostearate or ethyl cellulose etc.; Or the best Cera Flava that uses of component weight proportion: ethyl cellulose 6: 4.

8, according to claim 1 and 2 described a kind of preparations that improve bioavailability and medicine effect for treating gynecopathy, it is characterized in that: its The disintegrating agents of dispersible tablets is: crospolyvinylpyrrolidone, or carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, one or more of cross-linked carboxymethyl cellulose sodium etc., or component weight proportion the best is a carboxymethyl starch sodium: the mixture of low-substituted hydroxypropyl cellulose (1: 3); Binding agent in its described its dispersible tablet or the capsule is: 40% ethanol～95% alcoholic solution, or starch slurry, or the alcoholic solution of polyvinylpyrrolidone; Or the best is 50% alcoholic solution of 2～4% polyvinylpyrrolidones etc. one or more; Lubricant in its dispersible tablet is one or more of magnesium stearate or micropowder silica gel or Pulvis Talci etc.

9, according to claim 1 and 2 described a kind of preparations that improve bioavailability and medicine effect for treating gynecopathy, it is characterized in that: the adjuvant in its soft capsule content process for preparation is one or more of emulsifying agent, antiseptic etc.;

1) its emulsifying agent is: soybean lecithin, or select for use nonionic emulsifier as liquid egg phospholipid, or polyoxyethylene castor oil, or Oleum Cocois C8/C10 polyethyleneglycol glyceride, or almond oil acid polyethylene glycol glyceride, or polyoxyethylene (25) triolein, or tween 80, or Polyethylene Glycol-8-glycerol sad/one or more of decanoin etc.; The best almond oil acid polyethylene glycol glyceride that uses.

2) antiseptic is in its soft capsule: glycerol or propylene glycol or methyl parahydroxybenzoate, or ethylparaben, or propyl p-hydroxybenzoate or butyl p-hydroxybenzoate, or benzyl p-hydroxybenzoate, or one or more of P-hydroxybenzoic acid phenyl ester etc.

10; according to claim 1 and 2 described a kind of preparations that improve bioavailability and medicine effect for treating gynecopathy; it is characterized in that: described oiliness disperse medium is: the crude vegetal soybean oil; or the triglyceride oils of Oleum Arachidis hypogaeae semen or long-chain and medium-chain saturation in various degree; the oleic acid sorbitol ester; or component weight proportion olein: propylene glycol (90: 10); or Oleum Cocois C8/C10 monoglyceride or dibasic acid esters; or Oleum Cocois C8/C10 propylene glycol ester or Oleum Cocois triglyceride; or the acetylizad monoglyceride of purification or olein or glyceryl linoleate; or Polyethylene Glycol glyceryl laurate ester; or one or more of purification Oleum helianthi monoglyceride etc., or the best component weight proportion Oleum Cocois that uses: olein 9: 1.

11, according to claim 1 and 2 described a kind of preparations that improve bioavailability and medicine effect for treating gynecopathy, it is characterized in that: the filler during its preparation capsule is: starch, or lactose, or microcrystalline Cellulose, or precoking starch etc., or component weight proportion the best is a starch: precoking starch 5: 1; Disintegrating agent is: Sodium Tvlose, or precoking starch, or microcrystalline Cellulose, or crospolyvinylpyrrolidone, or low substituted carboxymethyl sodium cellulosate, or low-substituted hydroxypropyl cellulose, or polyvinylpyrrolidone, or one or more of carboxymethyl starch sodium etc., or the component weight proportion is best is low substituted carboxymethyl sodium cellulosate and 1: 1 mixture of carboxymethylstach sodium.