CN1634441A - Preparation for improving bioavailability and effect of golden pheasant and preparation method and purpose thereof - Google Patents

Abstract

The invention provides the preparation for improving bioavailability and effect of golden pheasant and preparation method and purpose thereof, wherein the preparation comprises (by weight ratio) root of Fructus Rosae Laevigatae 600-1000, mahonia stem 600-1000, spatholobus stem 1300-1700, shiny pricklyash 100-500, Moghania philippinensis 600-1000, green chiretta 200-300, by matching with adjuvant and base material, drop pill, soft capsule and dispersing tablet can be obtained.

Description

A kind of preparation and Preparation method and use that improves Jinji preparation bioavailability and drug effect

Technical field

The present invention relates to a kind of preparation and Preparation method and use that improves Jinji preparation bioavailability and drug effect, be used for the treatment of treatment male's chronic prostatitis or prostatauxe, or the pharmaceutical preparation of urinary system calculus.

Technical background

JINJI PIAN, JINJI JIAONANG, JINJI CHONGJI are the Chinese medicine compound that is used for the treatment of female pelvic inflammation, endometritis, cervicitis and leukorrhagia.JINJI PIAN has been listed in the 18 of the Drug Standard of Ministry of Public Health of the Peoples Republic of China " Chinese traditional patent formulation preparation ", and is national Chinese medicine protection kind.Former dosage form technical characterstic is that the Six-element medicinal substances extract adds appropriate amount of auxiliary materials and makes tablet.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.

Male's chronic prostatitis or prostatauxe, or urinary system calculus be the puzzlement men's health multiple disease, the invention discloses the golden pheasant novel formulation and be used for preparing the purposes for the treatment of above-mentioned disease medicament.

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 and use that improves Jinji preparation bioavailability and drug effect, the present invention to take following design: the component weight proportion of preparation of the present invention is:

1300～1700 parts of 600～1000 portions of Caulis Spatholobis of 600～1000 parts of Caulis Mahoniaes of Radix Rosae Laevigatae

200～300 parts of 600～1000 parts of Herba Andrographis of 100～500 parts of Radix Flemingiae Philippinensiss of Radix Zanthoxyli

Or preferable component weight proportion is:

1500 parts of 800 portions of Caulis Spatholobis of 800 parts of Caulis Mahoniaes of Radix Rosae Laevigatae

250 parts of 800 parts of Herba Andrographis of 300 parts of Radix Flemingiae Philippinensiss of Radix Zanthoxyli

Above-mentioned component cooperates the pharmaceutically alleged adjuvant or the substrate of the suitable kind of employing to make drop pill, soft capsule, dispersible tablet respectively.

As making drop pill with drop pill substrate; Or make dispersible tablet with filler, disintegrating agent, lubricant etc.; Or make soft capsule with disperse medium, suspending agent, antiseptic.

Radix Rosae Laevigatae: be root or the root bark of rosaceous plant leavigata Michx.

Radix Flemingiae Philippinensis: be the root of the climing property of leguminous plant Radix Flemingiae Philippinensis Flemingia philippinesis Merr.et Rolfe.Other medical materials all use by the record of document specifies such as Chinese Pharmacopoeia.

The extraction of the inventive method medical material prepares by following processing step:

The best component weight proportion of used medical material is:

1500 parts of 800 portions of Caulis Spatholobis of 800 parts of Caulis Mahoniaes of Radix Rosae Laevigatae

250 parts of 800 parts of Herba Andrographis of 300 parts of Radix Flemingiae Philippinensiss of Radix Zanthoxyli

The medicinal substances extract of above-mentioned component cooperates pharmaceutically alleged adjuvant that adopts suitable kind or drop pill, soft capsule, the dispersible tablet that substrate is made; As making drop pill with drop pill substrate (300～900 parts); Or make soft capsule with disperse medium (80～400 parts), suspending agent (5～10 parts), antiseptic (0.1～5 part); Or make dispersible tablet with filler (60～350 parts), disintegrating agent (15～100 parts), lubricant (0.5～5 part).

Step 1: the preparation of medicinal substances extract:

Get Six-element medical material in the prescription, decoct with water secondary, each 1.5～2.5 hours, filter, merging filtrate, being concentrated into relative density is the clear paste of 1.10～1.25 (55～60 ℃), is the medicinal substances extract of preparation drop pill or dispersible tablet or soft capsule; Or, be crushed to 100 orders～140 orders or thinner fine powder with the clear paste drying, also for preparing the medicinal substances extract of drop pill or dispersible tablet or soft capsule;

Step 2: drop pill or dispersible tablet or preparation of soft capsule:

The preparation of drop pill: it is 1.35～1.40 thick paste that above-mentioned clear paste is concentrated into relative density under 60 ℃ of conditions, with heat 300～900 parts melt and dissolved drop pill substrate and mix, make mix homogeneously, splash into molding in the coolant, remove coolant, promptly get drop pill, or coating gets coated drop pill after removing coolant, or

Preparation of soft capsule: get above-mentioned dried cream powder, with suspending agent (5～10 parts), 80～400 parts of disperse medium, antiseptic (0.1～5 part), modulation encystation liquid is promptly got the disperse medium that suspending agent is dissolved in part, be preheated to 60～65 ℃ standby; The antiseptic of getting the prescription share adds in the disperse medium of above-mentioned share remainder, stirs, and is mixed to 37 ℃ with above-mentioned disperse medium, adds medicinal substances extract, and mix homogeneously grinds homogenizing, promptly gets soft capsule liquid; Drip system or suppress and promptly get soft capsule.

The preparation of dispersible tablet:: get above-mentioned dried cream powder, with 60～350 parts filler, and 7～15 parts in even with disintegrating agent, 0.5～5 part mix lubricant, granulate with the wetting agent moistening, dry, granulate, 8～85 parts of the disintegrating agents that adding adds, tabletting, promptly get dispersible tablet, or coating promptly gets coated dispersing tablet behind the tabletting.

Drop pill substrate is that molecular weight is one or both the combination of 3500 to 11000 Polyethylene Glycol, and the best is a polyethylene glycol 6000: the mixture of Macrogol 4000 (8.5: 1.5); Condensing agent in its drop pill preparation is one of dimethicone, liquid paraffin, Oleum Camelliae, vegetable oil or two or more, and made drop pill can coatedly again be made coated drop pill, and coating fluid prescription is:

The drop pill coating solution: 87 parts of 5 parts of polyvinylpyrrolidones, 2 parts of PEG400s, 6 parts of acetyl monoglycerides, 70% ethanol, coating gained drop pill is smooth, fine and smooth.As in above-mentioned coating solution, adding the color lake, can make the coated drop pill of required color.

Disperse medium is oiliness disperse medium or water solublity disperse medium in the soft capsule;

1. the oil phase disperse medium is: olive oil or other crude vegetals, as soybean oil or Oleum Arachidis hypogaeae semen, or triglyceride oils, 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 one or more of Polyethylene Glycol glyceryl laurate ester or purification Oleum helianthi monoglyceride etc., or the best Oleum Cocois that uses: olein 9: 1;

2. water-soluble medium is: the Polyethylene Glycol of molecular weight 300～800, as: PEG400 or Polyethylene Glycol 500 or Macrogol 600, or the best PEG400 that uses.

The suspending agent of making soft capsule is: can increase the solid matter of disperse medium viscosity, as Cera Flava, aluminum monostearate, ethyl cellulose etc.; Its described antiseptic of making soft capsule is: one or more in glycerol, propylene glycol, methyl parahydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate, benzyl p-hydroxybenzoate, the P-hydroxybenzoic acid phenyl ester, or the best Cera Flava that uses of component weight proportion: ethyl cellulose 8: 2.

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

Filler in the dispersible tablet can be selected the filling adjuvant of general marketed tablet: as starch, precoking starch, microcrystalline Cellulose, lactose etc., dispersion effect is excellent to select precoking starch proportioning lactose, or best precoking starch: lactose was by 45: 30 part by weight.

The disintegrating agents of dispersible tablets is: crospolyvinylpyrrolidone, 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 crospolyvinylpyrrolidone (2: 5); Binding agent in its described its dispersible tablet is: the alcoholic solution of 40% ethanol～95% alcoholic solution or starch slurry or polyvinylpyrrolidone; Lubricant in its dispersible tablet is a magnesium stearate, or micropowder silica gel, or Pulvis Talci.

This dispersible tablet can coatedly again be made coated dispersing tablet, and coating solution makes dispersible tablet behind the bag film-coat owing to use special aqueous coatings material, still can satisfy the requirement of disintegrate in three minutes.

Coating solution is made up of polymer film-forming material, plasticizer and solvent etc., can also add surfactant as defoamer, coloring agent etc., or select commercially available finished product coating solution to be used.

A kind of preferable suitable XIANLING GUBAO film coating prescription is:

7% hypromellose (HPMC) (50%) alcoholic solution 1600g

Pulvis Talci 60g

Titanium dioxide 25g

Polyoxyethylene sorbitan monoleate 24g

Propylene glycol 18g;

The wherein effect of each component in the film coating liquid prescription:

1. hypromellose is the film-coat filmogen

2. ethanol is solvent

3. Pulvis Talci is a masking agent

4. titanium dioxide is masking agent

5. polyoxyethylene sorbitan monoleate is a plasticizer

6. propylene glycol is a plasticizer

On pharmaceutics, the present invention adopts above-mentioned film coating liquid to pack dispersible tablet, and making has dispersible tablet disintegrate at short notice and have smooth, clean and tidy outward appearance, overcome the bad outward appearance of the plain sheet of Chinese medicine, and overcome the defective that Chinese medicinal tablet usually needs to pack thicker sugar-coat.

Owing to the development of novel formulation, enlarged the therapeutic use of original Jinji preparation, especially in treatment chronic prostatitis, prostatauxe, the treatment aspect of urinary system calculus has demonstrated definite The pharmacological results.

One of effect of the present invention:

For objective evaluation golden pheasant (soft capsule, dispersible tablet, drop pill) novel form treatment chronic pelvic inflammatory disease clinical efficacy and safety, be contrast with the JINJI PIAN ordinary tablet, observe the curative effect situation of novel form:

Golden pheasant soft capsule group 62 examples (women), 11 examples of fully recovering (17.74%), produce effects 15 examples (24.19%), effective 32 examples (51.61%), invalid 4 examples (6.45%), total effective rate is 93.55%; Golden pheasant dispersible tablet group 63 examples (women), 12 examples of fully recovering (19.05%), produce effects 15 examples (23.81%), effective 33 examples (52.38%), invalid 3 examples (4.76%), total effective rate is 95.24%; , golden pheasant drop pill group 62 examples (women), 11 examples of fully recovering (17.82%), produce effects 16 examples (25.81%), effective 32 examples (51.61%), invalid 3 examples (4.84%), total effective rate is 95.16%; Matched group JINJI PIAN 64 examples (women), 11 examples of fully recovering (17.19%), produce effects 16 examples (25%), effective 32 examples (50.00%), invalid 5 examples (7.81%), total effective rate is 90.62%.Curative effect is checked through Ridit, P＞0.05, there was no significant difference; The tcm syndrome curative effect, there is significant difference the course of treatment and JINJI PIAN group comparison course of treatment P＜0.05 such as golden pheasant soft capsule group, dispersible tablet group, drop pill group, and the treatment group obviously is better than matched group.Through observing, treatment group (golden pheasant soft capsule, golden pheasant dispersible tablet, golden pheasant drop pill group) patient does not see obvious adverse reaction after taking medicine; Observation shows: treatment group (golden pheasant soft capsule, golden pheasant dispersible tablet, golden pheasant drop pill) has better clinical efficacy and drug safety to chronic pelvic inflammatory disease (syndrome of qi stagnation and blood stasis), obviously is better than matched group on drug treatment, shortens administration time.

1. case is selected

1.1 Western medicine diagnose standard

Related content formulation with reference to " new Chinese medicine clinical research guideline " (try), " obstetrics and gynecology " (national high medical college teaching material the 5th edition), " Chinese obstetrics and gynecology " (People's Health Publisher, 1999 June the 1st edition).

1.1.1 medical history: the acute pelvic inflammatory disease medical history is arranged more.

1.1.2 symptom: low grade fever, tired, lower abdomen weigh down expand pain or lumbosacral region distending pain, leucorrhoea grow in quantity, menoxenia, infertile.

1.1.3 sign: uterine activity is limited or adhesion is fixing with tenderness, attachment area (strand increases thick or lamellar thickens or enclosed mass) tenderness.

1.1.4 lab testing: A, routine blood test: can have total white blood cells or neutrophilic granulocyte slightly to increase; B, cervical canal secretions plate coating checking: can have unusual or detect pathogen.

1.1.5 ultrasound diagnosis: can visit and fallopian tube increases slightly, hydrops, or the pelvic inflammatory bag is fast.

1.2 tcm syndrome diagnostic criteria

Formulate with reference to " new Chinese medicine clinical research guideline " (trying), " Gynecology of Chinese Medicine " (high medical college teaching material the 4th, 5 editions) related content.

1.2.1 syndrome of qi stagnation and blood stasis

A, primary symptom: inferior belly gas pain or twinge, sore spot is fixed; Waist sacrum distending pain, abdominal pain during menstruation increases the weight of; Leucorrhea amount polychrome is white or yellow.

B, inferior disease: menorrhagia or menostaxis, dark red through color, folder clot, the breast side of body or distending pain of the breast.

C, tongue arteries and veins: dimly red tongue, or see petechia or ecchymosis, stringy pulse or puckery.

1.2.2 symptom scalar quantization standard:

A, primary symptom

A.1 hypogastralgia

There is not no pain.0 minute

End when doing during light pain.2 minutes

Middle pain is frequently shown effect.4 minutes

Heavy pain continues to exist.6 minutes

A.2 waist sacrum distending pain

No waist sacrum anacidity expands uncomfortable.0 minute

Light waist sacrum acid is expanded uncomfortable.2 minutes

Middle part of the side sacrum swelling and pain.4 minutes

Heavy waist sacrum distending pain is subjected to more unbearably.6 minutes

A.3 profuse leukorrhea

Not having does not have showed increased more at ordinary times.0 minute

Gently increase in 1/2 more at ordinary times.2 minutes

In increase 1/2 ~ 1 times more at ordinary times.4 minutes

Heavy increasing more at ordinary times more than 1 times.6 minutes

A.4 leucorrhea with yellow discharge

No leukorrhagia is normal.0 minute

Light leucorrhea with yellow discharge is held concurrently in vain mutually.2 minutes

Middle leucorrhea with yellow discharge.4 minutes

Yellow skin is green under the heave hand.6 minutes

B, inferior disease

B.1 abdominal pain during menstruation increases the weight of

Nothing stomachache nothing when row increases the weight of.0 minute

Have when gently when row, suffering from abdominal pain and increase the weight of.1 minute

In often have through when row stomachache and to increase the weight of.2 minutes

Heavy stomachache when row all increased the weight of at every turn.3 minutes

B.2 breast is coerced distending pain of the breast

Do not have normal.0 minute

Gently through the slight distending pain of preceding appearance.1 minute

In the distending pain discomfort appearred through preceding, menstrual period.2 minutes

Heavily continue to occur, distending pain is obvious.3 minutes

C, tongue arteries and veins

Describe and do not keep the score.

1.3 case is included standard in

1.3.1 meet chronic pelvic inflammatory disease Western medicine diagnose standard.

1.3.2 meet the tcm syndrome diagnostic criteria.

1.3.3 the age was at 18 ~ 50 years old.

1.4 case exclusion standard

1.4.1 do not meet chronic pelvic inflammatory disease Western medicine diagnose standard and tcm syndrome diagnostic criteria.

1.4.2 trimester of pregnancy or prepare gravid woman, women breast-feeding their children in the recent period.

1.4.3 merge to have the inclination, serious disease patients such as liver, kidney and hemopoietic system.

1.4.4 can't the partner, as be associated with nerve, mental disease, or be reluctant the partner.

1.4.5 allergic constitution or to multiple drug allergy person.

1.4.6 once adopted similar Drug therapy in the recent period, as took the medicine of relevant or phase antagonism, and caused curative effect of medication and be difficult to judgement person.

1.5 reject the case standard

1.5.1 after including in, find not meet to include standard person in.

1.5.2 do not use the medicine person after including in.

The case standard 1.6 come off

1.6.1 can't judge curative effect person's (, merge and use the other treatment medicine) not by the scheme medication.

1.6.2 untoward reaction occurs, should count the untoward reaction statistics.

2. physical data

2.1 age distribution: see Table 1.

The age distribution of table 1 case

18 ~ 30 years old 31 ~ 40 years old 41 ~ 50 years old

The total routine number of group

Example number % example number % example number %

Soft capsule group 62 15 24.19 38 61.29 9 14.52

Dispersible tablet group 63 16 25.40 37 58.73 10 15.87

Drop pill group 62 16 25.81 36 58.06 10 16.13

Matched group 64 17 26.56 36 56.25 11 17.19

Treatment group minimal ages 18 years old, maximum 48 years old age, average 33.66 ± 7.52 years old.Matched group minimal ages 21 years old, maximum 49 years old, average 35.29 ± 6.81 years old.Check through t: P＞0.05, relatively there was no significant difference has comparability.

2.2 the course of disease distributes: see Table 2

The table 2 case course of disease (year) distributes

≤ 1 year＞1 year ~≤5 years＞5 years

The total routine number of group

Example number % example number % example number %

Soft capsule group 62 34 54.84 21 33.87 7 11.29

Dispersible tablet group 63 35 55.56 20 31.75 8 12.70

Drop pill group 62 34 54.84 22 35.48 6 9.38

Matched group 64 35 54.69 22 34.38 7 10.94

The treatment group course of disease is the shortest 3 months, and is the longest 9 years, average 2.00 ± 1.23 years.The matched group course of disease is the shortest 4 months, and is the longest 10.5, average 1.89 ± 1.25 years.Check through t: P＞0.05, there was no significant difference.Has comparability.

3. observation index

3.1 general physical examination: body temperature, heart rate, blood pressure, pulse etc.

3.2 safety detects

3.2.1 blood, urine, just routine examination.(treatment before and after look)

3.2.2 the heart, hepatic and renal function inspection.(treatment before and after look)

3.2.3 untoward reaction that may occur and coherent detection index.The time of origin of itemized record untoward reaction, clinical symptoms, persistent period, treatment measures and extinction time.

3.3 health giving quality detects

3.3.1 related symptoms primary symptom, hold concurrently disease and the variation of tongue arteries and veins

Following abdominal distention pain; Waist sacrum distending pain, abdominal pain during menstruation increases the weight of; Leucorrhea amount polychrome is white or yellow; Menorrhagia or menostaxis, dark red through color, folder clot, the breast side of body or distending pain of the breast; Dimly red tongue, or see petechia or ecchymosis, stringy pulse or puckery.

3.3.2 relevant sign

3.3.2.1 ordinary circumstance body temperature, breathing, pulse, and blood pressure.

3.3.2.2 abdominal part sign tenderness, rebound tenderness, muscle tonus and abdominal distention, borborygmus change.

3.3.2.3 the variation of gynecologial examination uterus, fallopian tube ovary, the other connective tissue in palace and pelvic peritoneum inflammatory disease kitchen range.

3.3.3 relevant physico-chemical examination

A. peripheral blood leucocyte sum and neutrophilic granulocyte are counted; B. erythrocyte sedimentation rate; C.B is super to be checked; D cervical canal secretions plate coating checking.

4. observational technique

4.1 the employing random packet, contrast method, golden pheasant soft capsule group 62 examples, golden pheasant disperses chip level 63 examples, golden pheasant drop pill group 62 examples, matched group 64 examples.

4.2 dosage, number of times and the course of treatment

4.2.1 dosage, number of times

The treatment group:

The soft capsule group. oral golden pheasant soft capsule, each 2, every day 3 times, oral.Product batch number: 0306251, provide by Guangdong LuoFoshan Medicine Co., Ltd.

The dispersible tablet group. oral golden pheasant dispersible tablet, each 3, every day 3 times, oral.Product batch number: 0306161, provide by Guangdong LuoFoshan Medicine Co., Ltd.

The drop pill group. oral golden pheasant drop pill, each 40, every day 3 times, oral.Product batch number: 0306201, provide by Guangdong LuoFoshan Medicine Co., Ltd.

Matched group: oral JINJI PIAN, each 4, every day 3 times, oral.Product batch number: 0305251, produce by Hengsheng Pharmaceutical Co., Ltd., Zhongshan City.

4.2.2 the course of treatment: 30 days is a course of treatment, judges curative effect after all treating a course of treatment.

4.3 drug combination situation: except that the medicine that scheme is determined, other associated treatment medicine of stopping using.

4.4 the compliance measure of clinical trial: provide the information material of this test to experimenter or family members, the details of relevant clinical trial is described; With and right and possible being benefited.Clinical research person answers the patient and painstaking patient that treats, to obtain patient's trust.

4.5 untoward reaction is observed

4.5.1 main observe the malaise symptoms that occurs together with medication and allergy etc., and blood, urine, just conventional, cardiorenal function check unusual.Untoward reaction to duration of test occurs should be recorded in its kind, degree, time of occurrence, persistent period, treatment measures, pass through etc. on the observation table.

4.5.2 when untoward reaction occurring, observe the doctor and can whether stop clinical trial, the case because of the untoward reaction drug withdrawal is carried out tracing observation, its result of itemized record according to state of an illness decision.

4.5.3 in test as severely adverse event occurs, researcher should adopt suitable protective measure to the experimenter immediately, and report test director immediately, and the latter should report local medicine management department in 24 hours.

4.6 clinical trial record

4.6.1 all case should be observed in strict accordance with clinical protocol, conscientiously fills in the medical history record form.Record faithfully experimenter's medicining condition.

4.6.2 case history and medical history record form must not be changed as protocol, must not change protocol when doing any corrigendum, can only take additional description to give reasons, by the physician's signature who participates in clinical trial and date.

4.6.3 answer the various lab testing data of itemized record in the clinical trial, clinic case should stick on the initial report list on the medical history record.

4.6.4 the experimental data in normal range also should record, must be examined data significantly higher or beyond clinical tolerance interval, does necessary explanation by the doctor who participates in clinical trial.

5. observation of curative effect

5.1 efficacy determination

5.1.1 disease comprehensive therapeutic effect criterion

A. diseases such as recovery from illness treatment back hypogastralgia and waist sacrum distending pain disappear, and gynecologial examination and physico-chemical examination are normal.Syndrome sign integration and minimizing 〉=95%.Drug withdrawal is not recurred in January.

B. diseases such as produce effects treatment back hypogastralgia and waist sacrum distending pain disappear or obviously alleviate, and gynecologial examination and physico-chemical examination obviously improve.Syndrome sign integration and minimizing 〉=70%,＜95%.

C. effectively diseases such as treatment back hypogastralgia and waist sacrum distending pain alleviate, and gynecologial examination and physico-chemical examination make moderate progress.Syndrome sign integration and minimizing 〉=30%,＜70%.

D. disease nothing such as hypogastralgia and waist sacrum distending pain alleviates or has and increases the weight of after the futile treatment, and gynecologial examination and physico-chemical examination do not have before the treatment and improve or increase the weight of.Syndrome sign integration and minimizing＜30%.

5.1.2 therapeutic effect of syndrome criterion

A. the various transference cures in back are treated in recovery from illness, and the syndrome integrated value reduces 〉=95%.

B. each symptom of produce effects treatment back obviously alleviates, and the syndrome integrated value reduces 〉=70%,＜95%.

C. effectively each symptom of treatment back alleviates to some extent, and the syndrome integrated value reduces 〉=30%,＜70%.

D. each symptom does not have to alleviate or have and increases the weight of after the futile treatment, and the syndrome integrated value subtracts＜and 30%.

5.2 safety classification

There is not any untoward reaction, I. safely; Safety indexes is no abnormal.

II. compare safety, mild adverse effects is arranged, do not need to do any processing and can continue medication; Safety indexes is checked no abnormal.

III., safety issue is arranged, moderate untoward reaction is arranged, or the safety indexes inspection there is mile abnormality, can continue medication after dealing with.

IV. end to observe because of serious adverse reaction, or the safety indexes inspection is obviously unusual.

5.3 curative effect of disease is relatively:

Table 3 case curative effect of disease relatively

Recovery from illness produce effects enabledisable

The total routine number of group

Example number % example number % example number % example number %

Soft capsule group 62 11 17.74 15 24.19 32 51.61 4 6.45

Dispersible tablet group 63 12 19.05 15 23.81 33 52.38 3 4.76

Drop pill group 62 11 17.82 16 25.81 32 51.61 3 4.84

Matched group 64 11 17.19 16 25.00 32 50.00 5 7.81

Learn check by statistics, Ridit analyzes: P＞0.05, and there was no significant difference, treatment group curative effect and matched group are suitable.

Hypogastralgia, waist sacrum distending pain exponential integral (X ± S) relatively before and after the table 4 case treatment

Integration differential before the treatment

Group observation index example number treatment back integration

Soft capsule group 61 4.57 ± 0.79 1.53 ± 1.11 3.04 ± 1.70

The dispersible tablet group

62 4.26±0.82 1.35±0.89 3.10±1.07

Hypogastralgia

Drop pill group 60 4.43 ± 0.94 1.42 ± 1.21 3.23 ± 1.64

Matched group 59 4.62 ± 0.95 1.18 ± 0.95 3.44 ± 1.37

Soft capsule group 62 3.57 ± 1.50 0.53 ± 1.03 3.04 ± 1.64

The dispersible tablet group

63 3.67±1.52 0.49±0.67 3.12±1.34

Waist sacrum distending pain

The drop pill group

61 3.57±1.50 0.98±0.89 3.23±1.58

Matched group 62 3.39 ± 1.93 0.64 ± 1.50 2.75 ± 1.81

Before and after the treatment in the group relatively, t check P＜0.05, and significant difference is arranged, and treat forward and backward and matched group compares P＞0.05 there was no significant difference.

5.4 the tcm syndrome curative effect relatively

Syndrome integration comparison before and after the table 5 case treatment treatment (X ± S)

Integration differential before the treatment

Group example number treatment back integration

Soft capsule group 62 25.25 ± 3.24 2.53 ± 2.38 23.71 ± 7.45

Dispersible tablet group 63 25.38 ± 2.98 3.49 ± 2.13 23.56 ± 6.37

Drop pill group 62 26.63 ± 3.06 3.05 ± 2.19 22.64 ± 5.62

Matched group 64 26.55 ± 3.95 3.15 ± 7.75 23.40 ± 8.24

Group is relatively interior before and after the treatment, and t checks P＜0.05, and significant difference is arranged, and compares P＞0.05 there was no significant difference with matched group before and after the treatment.

5.5 the course of treatment relatively

Table 6 case compares the course of treatment

(X ± S) day group example number course of treatment

Soft capsule group 62 20.43 ± 2.97

Dispersible tablet group 63 19.27 ± 3.24

Drop pill group 62 18.05 ± 3.16

Matched group 64 24.55 ± 3.95

The course of treatment, relatively t checked P＜0.05, and significant difference is arranged.The treatment group obvious top grade course of treatment and matched group.

5.6 treatment group safety laboratory indexes check result

Table 7 treatment group safety laboratory indexes check result

Normal treatment back is unusual after normally treating preceding unusual the treatment before inspection item is treated

Erythrocyte 187 0 187 0

Leukocyte 0 187 173 14

Platelet 187 0 187 0

Routine urinalysis 187 0 187 0

Just conventional 187 0 187 0

Liver function 187 0 187 0

Renal function 187 0 187 0

Electrocardio Figure 187 0 187 0

Treatment group treatment proleukocyte does not increase person's 187 examples unusually.The former person's of increasing 173 routine the recoveries normally in treatment back, other 14 example have in various degree reduces, but does not return to normal level.

Platelet, routine urinalysis before and after the treatment, just indexs monitorings such as routine, liver function, renal function, electrocardiogram there is no unusually.The clinical observation treatment group is not seen obvious adverse reaction.

6. conclusion

Chronic pelvic inflammatory disease refers to internal genital organs of female (uterus, fallopian tube, broad ligament) connective tissue and pelvic peritoneum generation chronic inflammatory disease on every side, is common gynecologic inflammation.Chang Yinwei acute inflammation treatment not thoroughly or poor because of patient's body constitution, due to the state of an illness migration, clinical manifestation mainly contains that lower abdomen weighs down pain or lumbosacral region is ached, leucorrhea is many, menstruation is many, infertile etc.

Jinji preparation (soft capsule, dispersible tablet, drop pill) be by Radix Rosae Laevigatae, Caulis Mahoniae, Caulis Spatholobi, Fructus Zanthoxyli Dissiti, Radix Flemingiae Philippinensis, Herba Andrographis, etc. the compound Chinese patent medicine formed.The damp eliminating of being good for the stomach of Caulis Spatholobi blood circulation promoting and enriching in the side, Radix Rosae Laevigatae spleen reinforcing, Caulis Mahoniae, the broken swollen removing food stagnancy of Radix Flemingiae Philippinensis, the Radix Zanthoxyli relieving spasm to stop pain, the Herba Andrographis heat-clearing and toxic substances removing, Radix Angelicae Sinensis, Radix Codonopsis tonification gas, blood treatment chronic pelvic inflammatory disease compatibility is proper.

Clinical observation shows: golden pheasant soft capsule, golden pheasant dispersible tablet, golden pheasant drop pill treatment chronic pelvic inflammatory disease, course of disease weak point person curative effect is good especially, compares with JINJI PIAN, can obviously shorten administration time.Therapeutic effect is better than FUKE QIANJIN PIAN through check, and cure rate is higher.Especially for improving tcm syndrome, cardinal symptom (hypogastralgia, lumbosacral aching pain) aspect, significantly be better than contrasting tablet.

Two of effect of the present invention:

About the prostatitic pharmacological experiment study of golden pheasant novel formulation treatment andrology

1, materials and methods

1.1 40 of animal and grouping healthy SD male rats, body weight 150～250g.

Be divided into: JINJI PIAN treatment group (A), QIANLIEKANG treatment group (B), pathological model group (C), normal group (D), 10 every group.

1.2 modeling method is used, and 25% xiaozhiling injection 0.2ml injects A, B, C organizes and makes the scorching model of aseptic rat prostate in all animal prostate, injects the 0.5ml sterile saline in contrast in the D group prostate.

The major lesions of prostatitis pathological model is that inflammatory cell infiltration appears in prostata tissue, and body of gland destroys, and lumen of gland diminishes, obstructions such as proliferation of fibrous tissue and lumen of gland inflammatory endocrine.The scorching pathological model of the rat prostate of this experiment has tangible above-mentioned pathological changes, the model copy success.

1.3 medicine and Therapeutic Method

The A group gives Jinji preparation extract (8.0g/kg) and irritates the stomach treatment,

The B group gives QIANLIEKANG (8.0g/kg) and irritates the stomach treatment, and C, D group gives normal saline.1 time/day, treated continuously 30 days.

1.4 observation index Drug therapy to the 31 days adopts rat to pluck the eyeball method and gets blood examination and survey relevant index; All animals are put to death in dislocation of cervical vertebra then, get its prostate dorsal part leaf texture, are fixed in 10% formalin solution, conventional section, and hematoxylin, Yihong (HE) dyeing, light microscopic is observed down.The prostata tissue pathology; Endothelin level, thromboxane, prostaglandin; Superoxide dismutase (SOD), IgG.

All data of statistical method with " ± ' expression, through the check, data statistics SPSS10 software processes.

2 experimental results

Pathology (light microscopic) are observed D group capsule of prostate, mediastinum is all normal, in the alveolar lumen mediastinum obviously as seen, the wrinkle wall is abundant, obvious proliferation of fibrous tissue and inflammatory cell infiltration are seen in the end.C group prostate gland cell destroys, and brain matter obviously reduces, and part is stacking states, and lumen of gland diminishes, irregular, has tangible collagen fiber hypertrophy to hold around the interior non-viable non-apoptotic cell that as seen comes off, body of gland, visible a large amount of lymphocytic infiltrations in the substrate.A group prostate minority gland cell edema is arranged rule still.The lumen of gland form is slightly irregular, is flat or rugosity.Intracavity is seen a small amount of secretions, the slight atrophy of part body of gland.The outer erythrocyte of accidental blood vessel in heaps in the substrate, tangible fibroplasia and lymphocytic infiltration are seen in the end.B group prostate gland cell edema is obvious, the lumen of gland out-of-shape, and visible gland week of many places is folding.As seen see proliferation of fibrous tissue around the secreting type epithelial cell that comes off in the lumen of gland, body of gland, erythrocyte is full in the blood vessel, blood vessel peripheral lymphoid cell and a small amount of mast cells infiltration.Therefore, the have clear improvement pathological change of laboratory animal prostata tissue of golden pheasant novel formulation, its effect than QIANLIEKANG for well.

Three of effect of the present invention:

The pharmacological testing of JINJI PIAN treatment lithangiuria:

1 material

1.1 trial drug golden pheasant compound extract, every gram are equivalent to crude drug 15g gram, Pharma Inc. provides by the Luofu Mountain, Guangdong, faces the suspension that is mixed with desired concn with distilled water with preceding.Used herein golden pheasant compound extract dosage is the crude drug amount.

SHILINTONG PIAN contains Herba Lysimachiae extractum, by Luofu Mountain, Guangdong Pharma Inc., faces with preceding and is made into the suspension of desired concn with distilled water, and dosage is the extractum amount.

1.2 animal and feedstuff SD rat, the cleaning level.Commercially available complete feed.

Second two ferment feedstuffs are made pellet by ethylene glycol 500ml, ammonia chloride 250g and complete feed 24.75kg mix homogeneously, use for preparation second two ferment renal calculus animal models.

1.3 method

60 of ethylene glycol renal calculus rat models, body weight 203 ± 18g, male, be divided into 6 groups at random by the body weight segmentation, irritate stomach (10ml/kg) once a day for distilled water or medicine, altogether 4 weeks of administration.Feed common full-valence pellet feed as normal control, feed the ethylene glycol pellet and prepare renal calculus model river.

Put to death animal in 1 hour behind the last beginning medicine, take out the bilateral kidney rapidly, weigh and calculate the kidney coefficient; Vertically cut to the kidney back of the body from the hilus renalis with single-edge blade then, section up, covered with the cold light source irradiation, is put microscopically and is amplified 100 times and observe, and judges the calculus degree by following standard.

0 minute: the kidney section did not see that the sour calcium crystallization of leather forms, and section is smooth, and organizational structure is clear.

1 minute: the kidney section can be seen the calcium oxalate crystal that is dispersed in by chance, and normal position nephridial tissue section is smooth, and organizational structure is clear; Crystallization position organizational structure is fuzzyyer.

2 minutes: can see the calcium oxalate crystal that is dispersed in 2/3 the visual field, organize section and organizational structure together.

3 minutes: all can see in the visuals field and be dispersed in and do not have calcium oxalate crystal in heaps, or visible calcium oxalate crystal in heaps in flakes and do not see calcium oxalate crystal in other visuals field in 1/2 the visual field, organizational structure is unintelligible.

4 minutes: visible calcium oxalate crystal in heaps in the 2/3 above visual field, the calcium oxalate crystal that as seen is dispersed in other visuals field organized section rough, structure disturbance.

5 minutes: visible calcium oxalate crystal in heaps in whole visuals field, the nephridial tissue section was coarse, structure disturbance.

2 results

2.1 former influence and the normal control group to the ethylene glycol type large mouse with renal calculs of calculus compares, ethylene glycol renal calculus animal pattern weight loss, and kidney weight increases, and kidney coefficient and nephridial tissue water content obviously increase.Compare with model group, golden pheasant compound extract capsule does not have obvious influence to body weight, and kidney weight and kidney coefficient are slightly reduced, but no significant difference, SHILINTONG PIAN does not have obvious influence to body weight, kidney weight, but obviously reduces the kidney coefficient; The golden pheasant compound extract obviously reduces the nephridial tissue water content, and the effect of SHILINTONG PIAN reduction nephridial tissue water content is not obvious, sees Table 1.

Nephridial tissue water content and calculus degree are carried out regression analysis, find the obviously relevant (Y=0.9410 of nephridial tissue water content with the calculus degree, P＜0.05), the logical treated animal renal calculus degree of stranguria caused by urinary stone is similar to golden pheasant compound extract capsule small dose group animal calculus degree, also no significant difference of nephridial tissue water content between two groups.Animal pattern calculus degree obviously increases the weight of, and golden pheasant compound extract and stranguria caused by urinary stone are logical can to make the renal calculus degree obviously alleviate.

Table one

A is the nephridial tissue water content, and B is a kidney weight, and C is a body weight, and D is the calculus degree

Dosage kidney coefficient A B C D

Group

％ ％ g g g

Normal control 1.0 ± 0.1 80.5 ± 0.4 2.38 ± 0.26 234 ± 19 0.2 ± 0.4

Model contrast 1.4 ± 0.1 83.6 ± 0.8 2.92 ± 0.54 201 ± 31 4.3 ± 0.6

Golden pheasant compound extract 4.0 1.2 ± 0.2 81.0 ± 0.6 2.41 ± 0.33 194 ± 17 3.1 ± 0.6

Golden pheasant compound extract 8.0 1.2 ± 0.1 78.8 ± 0.7 2.40 ± 0.52 202 ± 38 2.8 ± 0.6

Golden pheasant compound extract 16.0 1.2 ± 0.2 76.4 ± 1.0 2.42 ± 0.60 196 ± 38 1.9 ± 0.7

Stranguria caused by urinary stone leads to compound extract 0.24 1.2 ± 0.2 76.8 ± 0.8 2.51 ± 0.48 204 ± 39 2.8 ± 0.5

2.2 the golden pheasant compound extract to ethylene glycol large mouse with renal calculs nephridial tissue mesoxalic acid and calcium content influence ethylene glycol renal calculus animal model nephridial tissue oxalic acid and calcium content obviously increases.Golden pheasant compound extract and stranguria caused by urinary stone are logical obviously to reduce calculus animal nephridial tissue oxalic acid and calcium content, sees Table 2

Table 2

Drug dose oxalic acid content calcium content

Group

g/kg mg/g mg/g

Normal control 1.6 ± 0.6 2.0 ± 1.2

Model contrast 8.6 ± 1.2 11.2 ± 2.4

Golden pheasant compound extract 4.0 6.0 ± 0.8 7.6 ± 1.9

Golden pheasant compound extract 8.0 5.3 ± 0.6 6.5 ± 0.8

Golden pheasant compound extract 16.0 4.2 ± 0.7 5.6 ± 2.2

The logical compound recipe of stranguria caused by urinary stone extracts 0.24

6.2±1.2 6.4±2.4

Thing

3 conclusions: this result of the test golden pheasant compound extract is to certain inhibitory action that is formed with of ethylene glycol large mouse with renal calculs calculus.The golden pheasant compound extract has obvious reduction effect to rat ethylene glycol renal calculus model renal tissue mesoxalic acid and calcium ion content, the principle of inferring its antigen road calculus may be because the ion concentration of calcium oxalate in tissue reduces, thereby reduced the formation that urinary system is organized mesoxalic acid calcium, suppressed calcium oxalate crystal in tissue deposition and work.Belonging to calcic type calculus as the lithangiuria more than 90%, is owing to oxalic acid, phosphoric acid or uric acid in calcium ion concentration rising and the urine in the urine form sour calcium calculus or other calculus.The golden pheasant compound extract obviously reduces calcium ion concentration in the nephridial tissue, suppresses the formation of calcium oxalate.

Advantage of the present invention is:

Drop pill: drop pill is the modern Chinese medicine novel form, belongs to solid dispersion system, and it is big to have specific surface area, and stripping is fast, the characteristics that bioavailability is high.And manufacturing cost is lower.Drops mostly is chemicals and uses, and the development of Chinese medicine dripping pills needs to test the choose reasonable substrate and make flow process by a large amount of.

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.

Former tablet is taken 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.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.

Male prostatitis, prostatauxe, urinary system calculus are the frequently-occurring diseases of puzzlement men's health, the invention discloses the purposes of Jinji preparation in these diseases of treatment.

The specific embodiment:

Embodiment 1: the preparation of Jinji preparation extract:

Medical material component weight proportion:

Radix Rosae Laevigatae 600g Caulis Mahoniae 600g Caulis Spatholobi 1300g

Radix Zanthoxyli 100g Radix Flemingiae Philippinensis 600g Herba Andrographis 200g

Get Six-element medical material in the above-mentioned prescription, decoct with water secondary, each 1.5 hours, filter, merging filtrate, being concentrated into relative density is the clear paste of 1.10 (55 ℃), is the medicinal substances extract of preparation drop pill or dispersible tablet or soft capsule; Or, be crushed to 100 purpose fine powders with the clear paste drying, also for preparing the medicinal substances extract of drop pill or dispersible tablet or soft capsule.

Embodiment 2: the preparation of Jinji preparation extract:

Medical material component weight proportion:

Radix Rosae Laevigatae 1000g Caulis Mahoniae 1000g Caulis Spatholobi 1700g

Radix Zanthoxyli 500g Radix Flemingiae Philippinensis 1000g Herba Andrographis 300g

Get Six-element medical material in the above-mentioned prescription, decoct with water secondary, each 2.5 hours, filter, merging filtrate, being concentrated into relative density is the clear paste of 1.25 (60 ℃), is the medicinal substances extract of preparation drop pill or dispersible tablet or soft capsule; Or, be crushed to 140 orders or thinner fine powder with the clear paste drying, also for preparing the medicinal substances extract of drop pill or dispersible tablet or soft capsule.

Embodiment 3: the preparation of Jinji preparation extract:

Medical material component weight proportion:

Radix Rosae Laevigatae 800g Caulis Mahoniae 800g Caulis Spatholobi 1500g

Radix Zanthoxyli 300g Radix Flemingiae Philippinensis 800g Herba Andrographis 250g;

Get above-mentioned Six-element medical material, decoct with water secondary, each 2.0 hours, filter, merging filtrate, being concentrated into relative density is 58 ℃ of clear paste under the condition, is the medicinal substances extract of preparation drop pill or dispersible tablet or soft capsule; Or, be crushed to 120 purpose fine powders with the clear paste drying, also for preparing the medicinal substances extract of drop pill or dispersible tablet or soft capsule;

Embodiment 4: the preparation of golden pheasant drop pill:

The component weight proportion

Drop pill substrate Macrogol 4000: polyethylene glycol 6000 (1.5: 8.5)

Step 1: get the medicinal substances extract of embodiment 1 or embodiment 2 or embodiment 3 preparations, get extract clear paste or dried cream powder, standby;

Step 2: preparation drop pill: it is 1.30 thick paste that above-mentioned clear paste is concentrated into relative density under 60 ℃ of conditions, or get the extract dried cream powder and be crushed to 100 orders and mix with the drop pill substrate that heats melt and dissolved 300g, make mix homogeneously, splash into molding in the coolant, remove coolant, promptly get drop pill, or coating gets coated drop pill after removing coolant;

Drop pill substrate in the drop pill is that molecular weight is 3000～12000 Polyethylene Glycol, or polyoxyethylene monostearate, or sodium stearate, or glycerin gelatine, or poloxamer, or stearic acid, or glyceryl monostearate, or cured one or more of worm, or the best is a polyethylene glycol 6000: the mixture of Macrogol 4000 (8.5: 1.5); Condensing agent in its drop pill preparation is one of dimethicone, liquid paraffin, Oleum Camelliae, vegetable oil or two or more, or the best is a component weight proportion methyl-silicone oil: liquid paraffin (8: 5).

The mixture that keeps medicinal substances extract and substrate when dripping system is in 75～90 ℃, 90 centimetres of cooling column effective column lengths, and 8 ℃ of liquid coolants are dripped 55 on fast every part of clock, dropper mouth external diameter 2.5mm, internal diameter 2.0mm, then dripping the drop pill of making does not have the tail of taking off, and outward appearance is bright and clean shaped.

Drip the drop pill make through removing coolant, can obtain outward appearance coated drop pill more attractive in appearance again through bag film-coat technology.Coating solution is made up of polymer film-forming material, plasticizer and solvent etc., and can also add surfactant as defoamer, coloring agent etc., or select commercially available finished product coating solution, as:

87 parts of 5 parts of polyvinylpyrrolidones, 2 parts of PEG400s, 6 parts of acetyl monoglycerides, 70% ethanol, coating gained drop pill is smooth, fine and smooth.As in above-mentioned coating solution, adding the color lake, can make the coated drop pill of required color.

Embodiment 5: the preparation of golden pheasant drop pill: the component weight proportion

Drop pill substrate Macrogol 4000: polyethylene glycol 6000 (1.5: 8.5)

Step 1: get the medicinal substances extract of embodiment 1 or embodiment 2 or embodiment 3 preparations, get extract clear paste or dried cream powder, standby;

Step 2: preparation drop pill: it is 1.35 thick paste that above-mentioned clear paste is concentrated into relative density under 60 ℃ of conditions, or get the extract dried cream powder and be crushed to 120 orders and mix with the drop pill substrate that heats melt and dissolved 600g, make mix homogeneously, splash into molding in the coolant, remove coolant, promptly get drop pill, or coating gets coated drop pill after removing coolant; Other system conditions are with embodiment 4.

Embodiment 6: the preparation of golden pheasant drop pill:

The component weight proportion

Drop pill substrate Macrogol 4000: polyethylene glycol 6000 (1.5: 8.5)

Step 1: get the medicinal substances extract of embodiment 1 or embodiment 2 or embodiment 3 preparations, get extract clear paste or dried cream powder, standby;

Step 2: preparation drop pill: it is 1.40 thick paste that above-mentioned clear paste is concentrated into relative density under 60 ℃ of conditions, or get the extract dried cream powder and be crushed to 140 orders and mix with the drop pill substrate that heats melt and dissolved 900g, make mix homogeneously, splash into molding in the coolant, remove coolant, promptly get drop pill, or coating gets coated drop pill after removing coolant; Other system conditions are with embodiment 4.

Embodiment 7: the golden pheasant preparation of soft capsule

Suspending agent Cera Flava 5g;

Disperse medium olive oil 80g;

Preservative propylene glycol 0.1g;

Emulsifying agent soybean lecithin 10g;

Step 1: get the medicinal substances extract of embodiment 1 or embodiment 2 or embodiment 3 preparations, get the dried cream fine powder of extract.

Step 2: preparation soft capsule: with modulation such as suspending agent 5g, disperse medium 80g, antiseptic 0.1g encystation liquid, promptly get the 50g disperse medium that suspending agent 5g is dissolved in part, be preheated to 60 ℃ standby; The antiseptic of getting 0.1g adds in the 30g disperse medium of above-mentioned share remainder, stirs, and is mixed to 37 ℃ with above-mentioned disperse medium and emulsifying agent 10 g, adds the dried cream fine powder of medicinal substances extract of step 1, and mix homogeneously grinds homogenizing, promptly gets soft capsule liquid; Drip system or suppress and promptly get soft capsule.

Cera Flava is a suspending agent, and the emulsifying agent soybean lecithin is an emulsifying agent in its soft capsule.

Propylene glycol is an antiseptic.

Olive oil is the oil phase disperse medium.Disperse medium is oiliness disperse medium or water solublity disperse medium;

1. the oil phase disperse medium is: olive oil or other crude vegetals, as soybean oil or Oleum Arachidis hypogaeae semen, or triglyceride oils, 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 one or more of Polyethylene Glycol glyceryl laurate ester or purification Oleum helianthi monoglyceride etc., or the best Oleum Cocois that uses: olein 9: 1;

2. water-soluble medium is: the Polyethylene Glycol of molecular weight 300～800, as: PEG400 or Polyethylene Glycol 500 or Macrogol 600, or the best PEG400 that uses.

The suspending agent of soft capsule is: can increase the solid matter of disperse medium viscosity, as Cera Flava, aluminum monostearate, ethyl cellulose etc.; Its described antiseptic of making soft capsule is: one or more in glycerol, propylene glycol, methyl parahydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate, benzyl p-hydroxybenzoate, the P-hydroxybenzoic acid phenyl ester, or the best Cera Flava that uses of component weight proportion: ethyl cellulose 8: 2;

Embodiment 8: the golden pheasant preparation of soft capsule

The component weight proportion:

Suspending agent second class cellulose 8g

Disperse medium PEG400 150g

Antiseptic glycerol 4g

Water 25ml

Emulsifier tween 80 0.5g

Step 1: get the medicinal substances extract of embodiment 1 or embodiment 2 or embodiment 3 preparations, get the dried cream fine powder of extract.

Step 2: preparation soft capsule; Get the 8g suspending agent be dissolved in the part the 100g disperse medium, be preheated to 62 ℃ standby; Get in the 50g disperse medium that the 4g antiseptic adds above-mentioned share remainder, stir, and be mixed to 37 ℃ with above-mentioned disperse medium and water 25ml and 0.5g emulsifier tween 80, the dried cream fine powder of medicinal substances extract that adds step 1, mix homogeneously grinds homogenizing, promptly gets soft capsule liquid; Drip system or suppress and promptly get soft capsule.

PEG400, water, glycerol are disperse medium, and Tween 80 is an emulsifying agent.Glycerol is held concurrently and is antiseptic.

Its adjuvant is selected with embodiment 7.

Embodiment 9: the golden pheasant preparation of soft capsule, and the component weight proportion:

Suspending agent Cera Flava 10g

Disperse medium olive oil 400g;

Preservative propylene glycol 5g;

Emulsifying agent soybean lecithin 10g;

Step 1: get the medicinal substances extract of embodiment 1 or embodiment 2 or embodiment 3 preparations, get the dried cream fine powder of extract.

Step 2: the preparation soft capsule: get the 10g suspending agent be dissolved in the part the 200g disperse medium, be preheated to 65 ℃ standby; Get in the 200g disperse medium that the 5g antiseptic adds above-mentioned share remainder, stir, and be mixed to 37 ℃ with above-mentioned disperse medium and 10g emulsifying agent soybean lecithin, add the dried cream fine powder of step 1 medicinal substances extract, mix homogeneously grinds homogenizing, promptly gets soft capsule liquid; Drip system or suppress and promptly get soft capsule.

Its adjuvant is selected with embodiment 7.

Embodiment 10: the preparation of golden pheasant dispersible tablet

The component weight proportion:

Filler: pregelatinized Starch 30g

Lactose 30g

Disintegrating agent crospolyvinylpyrrolidone 15g;

Lubricant: magnesium stearate 0.5g;

Correctives: xylitol 2g;

The dilute alcohol solution of polyvinylpyrrolidone

Step 1: get the medicinal substances extract of embodiment 1 or embodiment 2 or embodiment 3 preparations, get the extract dried cream powder,

Step 2: get above-mentioned dried cream powder, with the filler of 60g, and 7g in mix lubricant with disintegrating agent, 0.5g even, granulate with wetting agent moistening, binding agent, drying, granulate adds the disintegrating agent 8g that adds, tabletting, promptly get dispersible tablet, or coating promptly gets coated dispersing tablet behind the tabletting, make 1000 golden pheasant dispersible tablets.

The dilute alcohol solution of polyvinylpyrrolidone is polyvinylpyrrolidone 5g:20% ethanol 100ml.

Filler in the dispersible tablet can be selected the filling adjuvant of general marketed tablet: as starch, precoking starch, microcrystalline Cellulose, lactose etc., dispersion effect is excellent to select precoking starch proportioning lactose, or best precoking starch: lactose was by 45: 30 part by weight.

The disintegrating agents of dispersible tablets is: crospolyvinylpyrrolidone, 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 crospolyvinylpyrrolidone (2: 5); Binding agent in its described its dispersible tablet is: the alcoholic solution of 40% ethanol～95% alcoholic solution or starch slurry or polyvinylpyrrolidone; Lubricant in its dispersible tablet is a magnesium stearate, or micropowder silica gel, or Pulvis Talci.

This dispersible tablet can coatedly again be made coated dispersing tablet, and coating solution makes dispersible tablet behind the bag film-coat owing to use special aqueous coatings material, still can satisfy the requirement of disintegrate in three minutes.

Coating solution is made up of polymer film-forming material, plasticizer and solvent etc., can also add surfactant as defoamer, coloring agent etc., or select commercially available finished product coating solution to be used.

A kind of preferable suitable XIANLING GUBAO film coating prescription is:

7% hypromellose (HPMC) (50%) alcoholic solution 1600g

Pulvis Talci 60g

Titanium dioxide 25g

Polyoxyethylene sorbitan monoleate 24g

Propylene glycol 18g;

The wherein effect of each component in the film coating liquid prescription:

1. hypromellose is the film-coat filmogen

2. ethanol is solvent

3. Pulvis Talci is a masking agent

4. titanium dioxide is masking agent

5. polyoxyethylene sorbitan monoleate is a plasticizer

6. propylene glycol is a plasticizer

Embodiment 11: the preparation of golden pheasant dispersible tablet

The component weight proportion:

Filler: pregelatinized Starch 180g

Lactose 140g;

Disintegrating agent 24g;

Lubricant: magnesium stearate 4g;

Correctives is xylitol 3g;

The dilute alcohol solution of polyvinyl pyrrolidone

Step 1: get the medicinal substances extract of embodiment 1 or embodiment 2 or embodiment 3 preparations, get the extract dried cream powder,

Step 2: get above-mentioned dried cream powder, with the filler of 320g, and 10g in lubricant and the 3g correctives mix homogeneously of disintegrating agent, 4g, granulate with wetting agent moistening, binding agent, dry, granulate adds the disintegrating agent 14g that adds, tabletting, promptly get dispersible tablet, or coating promptly gets coated dispersing tablet behind the tabletting.

The dilute alcohol solution of polyvinylpyrrolidone is polyvinylpyrrolidone 3g:20% ethanol 100ml.

Filler in the dispersible tablet can be selected the filling adjuvant of general marketed tablet: as starch, precoking starch, microcrystalline Cellulose, lactose etc., dispersion effect is excellent to select precoking starch proportioning lactose, or best precoking starch: lactose was by 45: 30 part by weight.

The disintegrating agents of dispersible tablets is: crospolyvinylpyrrolidone, 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 crospolyvinylpyrrolidone (2: 5); Binding agent in its described its dispersible tablet is: the alcoholic solution of 40% ethanol～95% alcoholic solution or starch slurry or polyvinylpyrrolidone; Lubricant in its dispersible tablet is a magnesium stearate, or micropowder silica gel, or Pulvis Talci.

This dispersible tablet can coatedly again be made coated dispersing tablet, and coating solution makes dispersible tablet behind the bag film-coat owing to use special aqueous coatings material, still can satisfy the requirement of disintegrate in three minutes, and coating material is with embodiment 10.

Embodiment 12: the preparation of golden pheasant dispersible tablet

Filler: pregelatinized Starch 200g;

Lactose 150g;

Disintegrating agent: carboxymethyl starch sodium 100g;

Lubricant: micropowder silica gel 5g;

The dilute alcohol solution of wetting agent polyvinylpyrrolidone;

Step 1: get the medicinal substances extract of embodiment 1 or embodiment 2 or embodiment 3 preparations, get the extract dried cream powder.

Step 2: get above-mentioned dried cream powder, with the filler of 350g, and 15g in mix lubricant with disintegrating agent, 5g even, granulate with the wetting agent moistening, drying, granulate adds the disintegrating agent 85g that adds, tabletting promptly gets dispersible tablet, or coating promptly gets coated dispersing tablet behind the tabletting;

The dilute alcohol solution of polyvinylpyrrolidone is polyvinylpyrrolidone 5g:20% ethanol 100ml.

Filler in the dispersible tablet can be selected the filling adjuvant of general marketed tablet: as starch, precoking starch, microcrystalline Cellulose, lactose etc., dispersion effect is excellent to select precoking starch proportioning lactose, or best precoking starch: lactose was by 45: 30 part by weight.

The disintegrating agents of dispersible tablets is: crospolyvinylpyrrolidone, 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 crospolyvinylpyrrolidone (2: 5); Binding agent in its described its dispersible tablet is: the alcoholic solution of 40% ethanol～95% alcoholic solution or starch slurry or polyvinylpyrrolidone; Lubricant in its dispersible tablet is a magnesium stearate, or micropowder silica gel, or Pulvis Talci.

This dispersible tablet can coatedly again be made coated dispersing tablet, and coating solution makes dispersible tablet behind the bag film-coat owing to use special aqueous coatings material, still can satisfy the requirement of disintegrate in three minutes, and coating material is with embodiment 10.

Embodiment 13, a kind of preparation method that improves the preparation of Jinji preparation bioavailability and drug effect contain the discrimination method of Caulis Spatholobi in the golden pheasant dispersible tablet:

The preparation of need testing solution: get dispersible tablet 10g, 70ml grinds well with methanol, puts in the round-bottomed flask, puts water-bath and refluxes 2 times, each 45min takes out, and is cooled to room temperature, filters, merging filtrate, residue washed with methanol 3 times, each 10ml, washing liquid and filtrate merge, and water-bath volatilizes methanol, and residue adds the 20ml water dissolution, be transferred in the separatory funnel extraction 3 times (20,10,10ml) that adds diethyl ether, combining extraction liquid, water bath method, dissolve with methanol also is settled to 5ml, and is standby.

The medical material formulations prepared from solutions: take by weighing Caulis Spatholobi control medicinal material 5g, decocting boils 2 times, filters, and merging filtrate is concentrated into driedly, makes the 5ml methanol solution by the need testing solution preparation method, and is standby.

The negative formulations prepared from solutions of Caulis Spatholobi medical material; The medical material that takes by weighing except that Caulis Spatholobi in the prescription ratio is an amount of respectively, and the preparation method of pressing test sample is settled to 5ml, and is standby.

The TLC of Caulis Spatholobi differentiates and draws each 25 μ l of above-mentioned 2 kinds of solution, put respectively on same silica gel g thin-layer plate, with toluene: ethyl acetate (9: 5) is developing solvent, and ascending method is launched, and exhibition is apart from 14cm, take out, dry, the fluorescence speckle is observed at the 365nm place, in the test sample chromatograph, on the position corresponding, show the aeruginous fluorescence speckle of same color with the control medicinal material chromatograph; Spray is with 10% ethanol solution of sulfuric acid, and it is clear that hot blast blows to the speckle colour developing, and the fluorescence speckle is observed at the 365nm place, in the test sample chromatograph, on the position corresponding with the control medicinal material chromatograph, shows the faint yellow and yellow-green fluorescence speckle of same color.

Embodiment 14, a kind of novel formulation that improves Jinji preparation bioavailability and drug effect, adopt medical material to be:

1500 parts of 800 portions of Caulis Spatholobis of 800 parts of Caulis Mahoniaes of Radix Rosae Laevigatae

The preparation of the method preparation of 250 parts of 800 parts of Herba Andrographis of 300 parts of Radix Flemingiae Philippinensiss of Radix Zanthoxyli and the foregoing description can be used for preparation treatment chronic prostatitis or prostatauxe, or the medicine of urinary system calculus.

Claims (10)

1, a kind of preparation that improves Jinji preparation bioavailability and drug effect is characterized in that, used medical material component weight proportion is:

1300～1700 parts of 600～1000 portions of Caulis Spatholobis of 600～1000 parts of Caulis Mahoniaes of Radix Rosae Laevigatae

200～300 parts of 600～1000 parts of Herba Andrographis of 100～500 parts of Radix Flemingiae Philippinensiss of Radix Zanthoxyli;

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

2, a kind of preparation that improves Jinji preparation bioavailability and drug effect according to claim 1 is characterized in that, used medical material component weight proportion the best is:

1500 parts of 800 portions of Caulis Spatholobis of 800 parts of Caulis Mahoniaes of Radix Rosae Laevigatae

250 parts of 800 parts of Herba Andrographis of 300 parts of Radix Flemingiae Philippinensiss of Radix Zanthoxyli;

The medicinal substances extract of above-mentioned component cooperates pharmaceutically alleged adjuvant that adopts suitable kind or drop pill, soft capsule, the dispersible tablet that substrate is made; As making drop pill for 300～900 parts with drop pill substrate; Or make soft capsule for 0.1～5 part with 80～400 parts of disperse medium, 5～10 parts of suspending agents, antiseptic; Or make dispersible tablet for 0.5～5 part with 60～350 parts of filleies, 15～100 parts of disintegrating agents, lubricant.

3, a kind of formulation preparation method that improves Jinji preparation bioavailability and drug effect is characterized in that its method for making may further comprise the steps:

Step 1: the preparation of medicinal substances extract:

Get Six-element medical material in the prescription, decoct with water secondary, each 1.5～2.5 hours, filter, merging filtrate, being concentrated into relative density is the clear paste of 1.10～1.25 (55～60 ℃), is the medicinal substances extract of preparation drop pill or dispersible tablet or soft capsule; Or, be crushed to the above fine powder of 100 orders with the clear paste drying, also for preparing the medicinal substances extract of drop pill or dispersible tablet or soft capsule;

Step 2: drop pill or dispersible tablet or preparation of soft capsule:

The preparation of drop pill: getting above-mentioned clear paste, to be concentrated into relative density under 60 ℃ of conditions be 1.30～1.40 thick paste, with heat 300～900 parts melt and dissolved drop pill substrate and mix, make mix homogeneously, splash into molding in the coolant, remove coolant, promptly get drop pill, or coating gets coated drop pill after removing coolant;

Or preparation of soft capsule: get above-mentioned dried cream fine powder, mix with 5～10 parts of suspending agents, 80～400 parts of disperse medium, 0.1～5 part of antiseptic etc., modulation encystation liquid drips system or compacting promptly gets soft capsule;

Or the preparation of dispersible tablet: get above-mentioned dried cream fine powder, with 60～350 parts filler, and 7～15 parts disintegrating agent, 0.5～5 part mix lubricant even, granulate with the wetting agent moistening, dry, granulate adds 8～85 parts of disintegrating agents, tabletting again, promptly get dispersible tablet, or coating promptly gets coated dispersing tablet behind the tabletting.

4, a kind of preparation that improves Jinji preparation bioavailability and drug effect according to claim 1 and 2, it is characterized in that, drop pill substrate is that molecular weight is one or both combination of 3500 to 11000 Polyethylene Glycol, and the best is a polyethylene glycol 6000: the mixture of Macrogol 4000 (8.5: 1.5); Condensing agent in the preparation of its drop pill is one or more of dimethicone, liquid paraffin, Oleum Camelliae, vegetable oil.

5, a kind of preparation that improves Jinji preparation bioavailability and drug effect according to claim 1 and 2 is characterized in that, the disperse medium of making soft capsule is: be oiliness disperse medium or water solublity disperse medium;

1. the oil phase disperse medium is: olive oil or other crude vegetals, as soybean oil or Oleum Arachidis hypogaeae semen, or triglyceride oils, or 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 the Polyethylene Glycol glyceryl laurate ester, or one or more of purification Oleum helianthi monoglyceride etc., or the best Oleum Cocois that uses: olein 9: 1;

2. water-soluble medium is: the Polyethylene Glycol of molecular weight 300～800, as: PEG400, or Polyethylene Glycol 500, or Macrogol 600, or the best PEG400 that uses.

6, a kind of preparation that improves Jinji preparation bioavailability and drug effect according to claim 1 and 2, it is characterized in that its described antiseptic of making soft capsule is: 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, and as Cera Flava, or aluminum monostearate, or ethyl cellulose etc.; Or the best Cera Flava that uses of component weight proportion: ethyl cellulose 8: 2.

7, a kind of preparation that improves Jinji preparation bioavailability and drug effect according to claim 1 and 2, it is characterized in that, filler in its dispersible tablet is: starch or precoking starch or microcrystalline Cellulose or lactose etc., dispersion effect is excellent to select precoking starch proportioning lactose, or best proportioning is a precoking starch: lactose was by 45: 30 part by weight.

8, a kind of preparation that improves Jinji preparation bioavailability and drug effect according to claim 1 and 2, it is characterized in that, its The disintegrating agents of dispersible tablets is: crospolyvinylpyrrolidone, 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 crospolyvinylpyrrolidone (2: 5); Binding agent in its described its dispersible tablet is: the alcoholic solution of 40% ethanol～95% alcoholic solution or starch slurry or polyvinylpyrrolidone; Lubricant in its dispersible tablet is a magnesium stearate, or micropowder silica gel, or Pulvis Talci.

9, a kind of formulation preparation method that improves Jinji preparation bioavailability and drug effect according to claim 3 is characterized in that, comprises that discrimination method contains following steps:

The preparation of need testing solution: get drop pill, dispersible tablet, soft capsule content 10g respectively, 70ml grinds well with methanol, puts in the round-bottomed flask, puts water-bath and refluxes 2 times, each 45min, take out, be cooled to room temperature, filter, merging filtrate, residue washed with methanol 3 times, each 10ml, washing liquid and filtrate merge, water-bath volatilizes methanol, residue adds the 20ml water dissolution, is transferred in the separatory funnel, and extraction 3 times (20,10,10ml) adds diethyl ether, combining extraction liquid, water bath method, dissolve with methanol also is settled to 5ml, and is standby;

The control medicinal material formulations prepared from solutions: take by weighing Caulis Spatholobi control medicinal material 5g, decocting boils 2 times, filters, and merging filtrate is concentrated into driedly, makes the 5ml methanol solution by the need testing solution preparation method, and is standby;

The TLC of Caulis Spatholobi differentiates; Draw drop pill or dispersible tablet or the made need testing solution 25 μ l of soft capsule, with above-mentioned control medicinal material solution 25 μ l points on same silica gel g thin-layer plate, with toluene: ethyl acetate (9: 5) is developing solvent, and ascending method is launched, and exhibition is apart from 14cm, take out, dry, the fluorescence speckle is observed at the 365nm place, in the test sample chromatograph, on the position corresponding, show the aeruginous fluorescence speckle of same color with the control medicinal material chromatograph; Spray is with 10% ethanol solution of sulfuric acid, and it is clear that hot blast blows to the speckle colour developing, and the fluorescence speckle is observed at the 365nm place, in the test sample chromatograph, on the position corresponding with the control medicinal material chromatograph, shows the faint yellow and yellow-green fluorescence speckle of same color.

10, a kind of preparation purposes that improves Jinji preparation bioavailability and drug effect, used medical material is:

1500 parts of 800 portions of Caulis Spatholobis of 800 parts of Caulis Mahoniaes of Radix Rosae Laevigatae

250 parts of 800 parts of Herba Andrographis of 300 parts of Radix Flemingiae Philippinensiss of Radix Zanthoxyli

It is characterized by to be used for preparing and treat chronic prostatitis or prostatauxe, or the medicine of urinary system calculus.